PMID- 14946512
TI  - On fat peroxides in human polymorphonuclear leukocytes.

PMID- 14946513
TI  - Histochemical demonstration of ketosteroids in normal abnormal and neoplastic
      placentae.

PMID- 14946514
TI  - The histochemistry of lipid carbonyl compounds.

PMID- 14946515
TI  - Apparent identity of pigmented lipoid in cells in adrenal gland and interstitium
      of testis of mice following administration of stilbestrol.

PMID- 14946516
TI  - A new histochemical reaction for polysaccharides.

PMID- 14946517
TI  - The use of lead tetra-acetate to investigate the significance of the periodic
      acid-fuchsine sulfurous acid (PA-FSA) reaction.

PMID- 14946518
TI  - Histochemical methods for water-soluble, alcohol-insoluble polysaccharides and
      other substances oxidized to aldehydes by periodic acid.

PMID- 14946519
TI  - Vapor fixation of frozen sections for the preservation of the mucoid ground
      substance of Wharton's jelly.

PMID- 14946520
TI  - Fuchsin-aldehyde staining of sulfated mucopolysaccharides and related substances.

PMID- 14946521
TI  - The staining of mucopolysaccharides, with particular reference to those of cock's
      comb.

PMID- 14946522
TI  - Reductionin metachromasia of cartilage as an indicator of chondroitinase
      activity.

PMID- 14946523
TI  - Instrumentation for analytical cytology.

PMID- 14946524
TI  - Autoradiographic and staining observations on the use of carbowax as an embedding
      medium for frozen dried tissues.

PMID- 14946525
TI  - Autoradiographic visualization of atomic interexchange in various mineralized
      tissues.

PMID- 14946526
TI  - Enzyme activity of granules elaborated in mouse liver and spleen following
      intravenous injection of Th02.

PMID- 14946527
TI  - Nuclei and mitochondria in Escherichia coli cells infected with T2 bacteriophage.

PMID- 14946528
TI  - The differential staining of mitochondria and nuclei in mycobacteria.

PMID- 14946529
TI  - The determination of nucleic acids in single tissue sections.

PMID- 14946530
TI  - The quantitative histochemical estimation of nucleic acids and enzymatic activity
      in heterogeneous tissue.

PMID- 14946531
TI  - Mucoproteins of the connective tissue of the skin in generalized myxedema.

PMID- 14946532
TI  - Comparison of alkaline phosphatase activity in frozen and paraffin sections.

PMID- 14946533
TI  - Nuclear staining in the Gomori method for alkaline phosphatase.

PMID- 14946534
TI  - A new method for the histochemical demonstration of aryl sulfatase.

PMID- 14946535
TI  - A modification of the Gomori method avoiding the artifact staining of the
      nucleus.

PMID- 14946536
TI  - Alterations in chemical constituents and enzyme activity after freezing-drying
      and acetone fixation.

PMID- 14946537
TI  - Histochemical localization of acetyl cholinesterase in the central nervous system
      and myoneural junction.

PMID- 14946538
TI  - Studies in microabsorption spectroscopy of nerve cells.

PMID- 14946539
TI  - The nucleic acid content of gray matter (anterior column) of the spinal cord
      following axonal section.

PMID- 14946540
TI  - Histological staining with methyl green-pyronin.

PMID- 14946541
TI  - A comparison of the estimation of desoxyribose nucleic acid (DNA) in isolated
      animal nuclei by ultraviolet microspectrophotometry and by biochemical analysis.

PMID- 14946542
TI  - The psychotherapeutic aspects of schizophrenia.

PMID- 14946543
TI  - The role of the cerebral cortex in the dynamics of personality as a holistic
      organism-environment system.

PMID- 14946544
TI  - An electromyographic investigation of tense and relaxed subjects.

PMID- 14946545
TI  - Bilateral cervical sympathectomy with stellate ganglionectomy in essential
      hypertension.

PMID- 14946547
TI  - BOSTON Society of Psychiatry and Neurology.

PMID- 14946546
TI  - Psychosis in polycythemia vera.

PMID- 14946548
TI  - Psychogenic motor phenomena in the presence of an abnormal electroencephalogram.

PMID- 14946549
TI  - Brain dynamics and psychic activity.

PMID- 14946550
TI  - Hemiballismus: hemichorea following a lesion of the corpus luysi.

PMID- 14946551
TI  - Hypnotherapy of a patient with an animal phobia.

PMID- 14946552
TI  - On eyedness in homonymous hemianopia.

PMID- 14946553
TI  - Paroxysmal high voltage and rhythmic low voltage discharges from isolated and
      partially isolated human cortex.

PMID- 14946554
TI  - Studies on headache: further observations on cranial and conjunctival vessels
      during and between vascular headache attacks.

PMID- 14946555
TI  - Failures in migraine therapy.

PMID- 14946556
TI  - Effects of hypnotic suggestion of pain perception and galvanic skin responses.

PMID- 14946557
TI  - Papilledema and poliomyelitis.

PMID- 14946558
TI  - The electroencephalogram in the electric shock therapies.

PMID- 14946559
TI  - Carbon dioxide inhalation therapy in the management of the psychoses.

PMID- 14946560
TI  - Newer techniques in psychosurgery.

PMID- 14946561
TI  - A critical survey of fifty spinal fractures due to electric shock treatments.

PMID- 14946562
TI  - A statistical analysis of 1994 veteran patients.

PMID- 14946563
TI  - The Guillain-Barre Syndrome.

PMID- 14946565
TI  - Physiologic changes following frontal lobe surgery in chronic mental illness.

PMID- 14946564
TI  - Hypnotherapy. II.

PMID- 14946566
TI  - Observations on dynamic changes after prefrontal lobotomy.

PMID- 14946567
TI  - SIR Charles Scott Sherrington, O.M. (1857-1952).

PMID- 14946568
TI  - Effect of ablation of prestriate cortex on auditory-visual association in monkey.

PMID- 14946569
TI  - Sites of origin of electric potentials in striate cortex.

PMID- 14946570
TI  - Observations on the mechanism of experimental cerebellar seizures.

PMID- 14946571
TI  - Maximum conduction velocities of motor fibers of ulnar nerve in human subjects of
      various ages and sizes.

PMID- 14946572
TI  - Cortical projection zone of chorda tympani nerve in cat.

PMID- 14946573
TI  - LUDWIG Edinger 1855-1918.

PMID- 14946574
TI  - The cerebellar angioreticulomas.

PMID- 14946575
TI  - Neurophysiological studies on cerebral concussion.

PMID- 14946576
TI  - Localized encephalitis, brain abscess and subdural empyema.

PMID- 14946577
TI  - Trigeminal neuralgia; a review of six hundred and eighty-nine cases with a follow
      up study of sixty five per cent of the group.

PMID- 14946578
TI  - Effects of intracarotid administration of nitrogen mustard on normal brain and
      brain tumors.

PMID- 14946579
TI  - An evaluation of palliative surgical procedures in trigeminal neuralgia.

PMID- 14946580
TI  - An unusual case of unilateral eighth nerve tumor.

PMID- 14946581
TI  - Benign arachnoid cysts of the posterior fossa.

PMID- 14946582
TI  - Colloid cyst of the fourth ventricle; report of a case of two colloid cysts of
      the fourth ventricle.

PMID- 14946583
TI  - Gliomatosis cerebri.

PMID- 14946584
TI  - Bed attachment for improved head traction.

PMID- 14946585
TI  - An attempt to produce hemochromatosis experimentally and the effect of high
      levels of copper and choline in the diet.

PMID- 14946586
TI  - Relationships between intake and serum levels of ascorbic acid, vitamin A, and
      carotene of selected groups of children with physical signs of vitamin
      deficiencies.

PMID- 14946587
TI  - Tocopherol content of human milk and of cows' milk products used for infant
      feeding.

PMID- 14946588
TI  - Growth response and vitamin B12 tissue levels in vitamin B12-deficient rats and
      chicks fed riboflavin, 5,6-dimethylbenzimidazole and related compounds.

PMID- 14946589
TI  - Effect of fasting or protein depletion upon body weight, and fat, nitrogen, and
      choline content of livers of choline-deficient rats.

PMID- 14946590
TI  - The effect of dietary fat on the reproductive performance and the mixed fatty
      acid composition of fat-deficient rats.

PMID- 14946591
TI  - The measurement of fat absorption and distribution using eleostearic acid.

PMID- 14946592
TI  - Total plasma protein and plasma fibrinogen in ascorbic acid deficiency and scurvy
      in the monkey.

PMID- 14946593
TI  - The effect of processing on the enzymatic liberation of lysine and arginine from
      soybean oil meal.

PMID- 14946594
TI  - Factors affecting the percentage of certain proteins in egg white.

PMID- 14946595
TI  - The effects of heat on the nutritive value of protein hydrolysates with dextrose.

PMID- 14946596
TI  - Influence of age and of sex of the albino rat on hepatic ascorbic acid.

PMID- 14946597
TI  - The aspartic acid, glutamic acid, proline and tyrosine content of meat.

PMID- 14946598
TI  - The occurrence of a calcinosis syndrome in the cotton rat. I. The effect of diet
      on the ash content of the heart.

PMID- 14946599
TI  - The occurrence of a calcinosis syndrome in the cotton rat. II. Pathology.

PMID- 14946600
TI  - Daily determination of plasma, serum and white cell-platelet ascorbic acid in
      relationship to the excretion of ascorbic and homogentisic acids by adults
      maintained on a controlled diet.

PMID- 14946601
TI  - The effect of testosterone propionate on niacin metabolism in rats.

PMID- 14946602
TI  - The importance of choline in the prevention of nutritional edema in rats fed low
      protein diets.

PMID- 14946603
TI  - A study of lysine deficiency and nitrogen balance under ad libitum and force
      feeding conditions.

PMID- 14946604
TI  - The influence of ingested mineral oil upon the development of an essential fatty
      acid deficiency in the rat.

PMID- 14946605
TI  - Nutritive value of lard as affected by the proportion of fat in the diet.

PMID- 14946606
TI  - The riboflavin requirement of the baby pig. I. At an environmental temperature of
      85 F. and 70% relative humidity.

PMID- 14946607
TI  - The amount of nitrogen retained by 6 young women on an intake of approximately 70
      GM of protein a day.

PMID- 14946608
TI  - Nitrogen balance of adult rats fed diets low in l-, dl- and d-phenylalanine.

PMID- 14946609
TI  - Application of the chromic oxide indicator method to balance studies with growing
      chickens.

PMID- 14946611
TI  - The characteristics of tritanopia.

PMID- 14946610
TI  - Vitamin B12 requirement of weanling pigs. II. Performance on low levels of
      vitamin B12 and requirement for optimum growth.

PMID- 14946612
TI  - The effect of high intensity and short duration versus low intensity and long
      duration of intermittent pre-exposure upon human dark adaptation.

PMID- 14946613
TI  - The visibility of black objects against an illuminated background.

PMID- 14946614
TI  - Strictly manipulative.

PMID- 14946615
TI  - Specific osteopathic manipulate treatment.

PMID- 14946616
TI  - FOUNDER'S day program complete for 1952 observance at Kirksville.

PMID- 14946617
TI  - Five states report progress with rural health attack at local level.

PMID- 14946618
TI  - Rural health: an obligation.

PMID- 14946619
TI  - Superinfection in relation to the indiscriminate use of antibiotics.

PMID- 14946620
TI  - Doctor's bonus law.

PMID- 14946621
TI  - Livestock parasitology in the United States.

PMID- 14946622
TI  - New blood flukes (Trematoda: Spirorchidae) from the marine turtle, Chelonia mydas
      (L.).

PMID- 14946623
TI  - The biology and life history of Monoecocestus beddard, 1914 (Cestoda:
      Anoplocephalidae) from the porcupine.

PMID- 14946624
TI  - Parasitism of mosquito larvae by mermithids (Nematoda).

PMID- 14946625
TI  - The reproductive potential of five species of coccidia of the chicken as
      demonstrated by oocyst production.

PMID- 14946626
TI  - The male of Dermacentor dissimilis cooley (Acarina: Ixodidae).

PMID- 14946627
TI  - Two new Venezuelan chiggers (Acarina: Trombiculidae).

PMID- 14946628
TI  - A new species of isospora, I. Xantusiae, from Southern California lizards.

PMID- 14946629
TI  - Helminths from the roundtailed muskrat, Neofiber alleni nigrescens howell, with
      descriptions of two new species.

PMID- 14946630
TI  - A new Xiphidiocercaria, C. goodmani, from Lymnacea palustris.

PMID- 14946631
TI  - Cercaria myae sp. nov., a fork-tailed larva from the marine bivalve, Mya
      arenaria.

PMID- 14946632
TI  - The life cycle of Conspicuum icteriodorum Denton and Byrd, 1951. (Trematoda:
      Dicrocoeliidae).

PMID- 14946633
TI  - On the tissue phase of the life cycle of the fowl nematode Ascaridia galli
      (Schrank).

PMID- 14946634
TI  - Sylvatic plague studies. VIII. Notes on the alimentary and reproductive tracts of
      fleas, made during experimental studies of plague.

PMID- 14946635
TI  - The survival of Toxoplasmagondii in various suspending media.

PMID- 14946636
TI  - Cecal coccidiosis and carbohydrate metabolism in chickens.

PMID- 14946637
TI  - An anomalous tapeworm from man.

PMID- 14946638
TI  - Contributions to the morphology and life-history of Gynaecotyla adunca (Linton,
      1905) (Trematoda: Microphallidae).

PMID- 14946639
TI  - The relation of Culicoides (Diptera: Heleidae) to the transmission of onchocerca
      volvulus.

PMID- 14946640
TI  - Pomatiopsis lapidaria, its occurrence in the Washington, D.C. area and its
      laboratory rearing in comparison to that of Oncomelania spp.

PMID- 14946641
TI  - Studies on the trematode family Cyathocotylidae poche, 1926, with the description
      of a new species of Holostephanus from fish and the life history of Prohemistomum
      chandleri sp. nov.

PMID- 14946642
TI  - Helminths of northwestern mammals. II. Oligorchis nonarmatus N. sp. (Cestoda:
      Hymenolepididae) from the yellowbellied squirrel.

PMID- 14946643
TI  - Studies on the life cycle and biology of monoecocestus sigmodontis (Cestoda:
      Anoplocephalidae) from the cotton rat, sigmodon hispidus.

PMID- 14946644
TI  - Another annelid first intermediate host of a digenetic trematode.

PMID- 14946645
TI  - Collections of ectoparasitic mites from Alaska.

PMID- 14946646
TI  - The comparative tissue reaction of two strains of Australorbis glabratus to
      infection with Schistosomia mansoni.

PMID- 14946647
TI  - PROGRAM and abstracts of the twenty seventh annual meeting of the American
      Society of Parasitologists, Cornell University, Ithaca, N.Y.

PMID- 14946648
TI  - The agglutinating property of complement.

PMID- 14946649
TI  - The effect of intermittent anoxia on the brain.

PMID- 14946650
TI  - The histological changes produced in the rat testis by temporary and permanent
      occlusion of the testicular artery.

PMID- 14946651
TI  - The reciprocal resistance to various amino-acids of strains of Bact. coli made
      resistant to one of them.

PMID- 14946652
TI  - Laryngeal histoplasmosis simulating carcinoma.

PMID- 14946653
TI  - Submicroscopical changes in muscles of vitamin E deficient rabbits.

PMID- 14946654
TI  - Fibrinoid necrosis in rheumatic fever.

PMID- 14946655
TI  - An unusual case of hyperglobulinaemia.

PMID- 14946656
TI  - An illustrated scheme for the microscopic identification of the rumen
      microorganisms of sheep.

PMID- 14946657
TI  - A fatal case of intestinal lipodystrophy of Whipple investigated during life.

PMID- 14946658
TI  - Rheumatio-like lesions in the heart of the rabbit experimentally induced by
      repeated inoculation with haemolytic streptococci.

PMID- 14946660
TI  - Globular thrombi and perivascular myelin breakdown.

PMID- 14946659
TI  - A negative correlation between size and number of the erythrocytes of cows,
      sheep, goats and horses.

PMID- 14946661
TI  - The pathology of hepatitis.

PMID- 14946662
TI  - A meningioma causing nasal polypi of brain tissue.

PMID- 14946663
TI  - Tubercle bacilli in haematomata.

PMID- 14946664
TI  - The multiplication of complement-fixing antigen and red-cell agglutinin in the
      chorio-allantoic membrane of fertile eggs inoculated with influenza virus.

PMID- 14946665
TI  - Leishman's staining of soft and bony tissues in paraffin sections.

PMID- 14946666
TI  - The inhibition of the hydrolysis of procaine and 2-chloroprocaine in plasma by
      neostigmine and dimethylcarbamate of (2-hydroxy-5-phenylbenzyl) trimethylammonium
      bromide (Ro-2-683).

PMID- 14946667
TI  - The hydrolysis of procaine and 2-chloroprocaine in spinal fluid.

PMID- 14946668
TI  - Phenol studies XII. The percutaneous and alimentary absorption of phenol by
      rabbits with recommendations for the removal of phenol from the alimentary tract
      or skin of persons suffering exposure.

PMID- 14946669
TI  - The gastrointestinal non-absorption of sodium cellulose sulfate labeled with S35.

PMID- 14946670
TI  - The effect of perfusion pressure on papaverine vasodilatation in rabbit hearts.

PMID- 14946671
TI  - Quinidine-like activity of thephorin.

PMID- 14946672
TI  - The distribution, metabolism, and excretion of d-tubocurarine chloride and
      related compounds in man and other animals.

PMID- 14946673
TI  - Mechanism of veratrum-induced emesis in the cat.

PMID- 14946674
TI  - Autonomic blocking compounds. I. Ganglion blocking action of some aliphatic
      quaternary ammonium salts, related alkyl piperidinium salts and 1,2,3,4
      tetrahydroisoquinolinium salts.

PMID- 14946675
TI  - Toxicological studies of a new mercurial diuretic: mercumatilin (cumertilin).

PMID- 14946676
TI  - The effect of amphetamine and related compounds on maze performance of white
      rats.

PMID- 14946677
TI  - The relationship between cholinesterase inhibition and ganglionic transmission.

PMID- 14946678
TI  - The effect of cortisone, desoxycorticosterone, adrenocorticotrophic hormone and
      diphenhydramine upon the responses of albino mice to general anesthetics.

PMID- 14946679
TI  - Effects of liver injury and nephrectomy on the anticonvulsant activity of
      oxazolidine-2,4-diones.

PMID- 14946680
TI  - Studies on cell enzyme systems. VII. Luciferase inactivation by alcohols.

PMID- 14946681
TI  - The applications of ultraviolet absorption spectrophotometry in pharmaceutical
      analysis.

PMID- 14946682
TI  - A sterility test for neoarsphenamine B.P. and sulpharsphenamine B.P. for
      injection.

PMID- 14946683
TI  - The survival of bacterial spores in arsphenamines.

PMID- 14946684
TI  - The effects of thiouracil, alloxan and nicotine on the suprarenal glands.

PMID- 14946685
TI  - PREPARATION and testing of the provisional British standard for globin zinc
      insulin.

PMID- 14946686
TI  - The effects of introducing certain suggested substitutes for talc into the
      peritoneal cavity and into wounds in experimental animals.

PMID- 14946687
TI  - The application of titration in non-aqueous media to pharmaceutical analysis. I.
      The determination of alkali metal salts of aliphatic and aromatic acids.

PMID- 14946688
TI  - A note on the estimation of isonicotinic acid hydrazide.

PMID- 14946689
TI  - Analgesics--a general survey.

PMID- 14946690
TI  - The chemistry of antipernicious anaemia factors.

PMID- 14946691
TI  - The antagonism and synergism of histamine and antihistamines in mice.

PMID- 14946692
TI  - The structure of the flower of Datura innoxia Miller.

PMID- 14946693
TI  - The spectrophotometric detection and estimation of procaine hydrochloride in
      aqueous solution.

PMID- 14946694
TI  - ULTRA-violet spectrophotometric assay of alkaloids. I. Strychnine in the presence
      of brucine.

PMID- 14946695
TI  - [Contribution to the experimental study of vagotomy on the gastric physiology].

PMID- 14946696
TI  - [The effect of thermal shock alone or associated with hypophysectomy or insulin
      on the reactive capacity of the rat liver to the glycogenolytic action of
      adrenaline].

PMID- 14946697
TI  - [The action of strychnine on the spinal reflex activity; electrophysiology].

PMID- 14946698
TI  - [Electric variations in the psychogalvanic reflex at the cutaneous effector].

PMID- 14946699
TI  - [Nor-adrenaline, a product normally secreted by the adrenal gland under the
      influence of excitation of a great splanchnic nerve].

PMID- 14946700
TI  - [The relations between the rapidity of hydrolysis of different choline esters by
      benzoylcholinesterase and the chemical constitution of the substrates].

PMID- 14946701
TI  - [The physiological significance of the refractory period in the sexual behavior
      of the male rat].

PMID- 14946702
TI  - [The influence of nutrition on the magnitude of respiratory exchanges in the
      rabbit].

PMID- 14946703
TI  - [Calcium exchanges in the rat during pregnancy, lactation and weaning. 1. The
      effect of a calcium rich diet].

PMID- 14946704
TI  - [The nyctohemeral rhythm of the temperature and of heart production].

PMID- 14946705
TI  - [The mechanism of economy of vitamin C; effects of paraaminophenylsulfamide on
      the vascular actions of vitamin C and catechin].

PMID- 14946706
TI  - [A simple procedure for blood sampling in the rat].

PMID- 14946707
TI  - The spatial distribution of dividing cells in the liver of the rat after partial
      hepatectomy.

PMID- 14946708
TI  - The relation of dorsal and ventral root potentials to reflex activity in mammals.

PMID- 14946709
TI  - A comparison of arm-bag sweat and body sweat.

PMID- 14946710
TI  - The effect of arterial occlusion on sweat composition.

PMID- 14946711
TI  - The influence of insulin on the permeability of the blood-aqueous barrier to
      glucose.

PMID- 14946712
TI  - Measurement of current-voltage relations in the membrane of the giant axon of
      Loligo.

PMID- 14946713
TI  - Currents carried by sodium and potassium ions through the membrane of the giant
      axon of Loligo.

PMID- 14946714
TI  - The components of membrane conductance in the giant axon of Loligo.

PMID- 14946715
TI  - The dual effect of membrane potential on sodium conductance in the giant axon of
      Loligo.

PMID- 14946716
TI  - The effect of calcium ions on the motor end-plate potentials.

PMID- 14946717
TI  - PROCEEDINGS of the physiological society Department of physiology, Royal Free
      Hospital School of Medicine, Hunter Street and Institute of Ophthalmology, Judd
      Street, London, W.C.1. 19 January 1952.

PMID- 14946718
TI  - A simple vibrator for kymograph recording.

PMID- 14946719
TI  - A scintillation gamma-counter for radio-potassium.

PMID- 14946720
TI  - An apparatus for testing visual discrimination in cats.

PMID- 14946721
TI  - Comparative studies of the distribution of chloride between plasma and aqueous
      humour.

PMID- 14946722
TI  - An electromyographic study of the role of the abdominal muscles in breathing.

PMID- 14946723
TI  - Interchangeability of diet and light in rat breeding.

PMID- 14946724
TI  - The behaviour of radio-potassium in man.

PMID- 14946725
TI  - The permeability of interstitial connective tissue and the nature of the
      interfibrillary substance.

PMID- 14946726
TI  - The reflex activity of the respiratory centre.

PMID- 14946727
TI  - Persistent 24-hour renal excretory rhythm on a 12-hour cycle of activity.

PMID- 14946728
TI  - The effect of inhalation of high and low concentrations of oxygen on the
      respiration of the premature infant.

PMID- 14946729
TI  - The effect of carotid occlusion upon the intrasinusal pressure with special
      reference to vascular communications between the carotid and vertebral
      circulations in the dog, cat and rabbit.

PMID- 14946730
TI  - The force exerted by active striated muscle during and after change of length.

PMID- 14946731
TI  - The excitability of a single fiber in a nerve trunk.

PMID- 14946732
TI  - Spontaneous subthreshold activity at motor nerve endings.

PMID- 14946733
TI  - Collagen in regenerating liver of the rat.

PMID- 14946734
TI  - Changes in the liver of the rat after partial hepatectomy.

PMID- 14946735
TI  - The exchangeability of the potassium of frog muscle, studied in phosphate media.

PMID- 14946736
TI  - The relation between the volume of a test-meal and the gastric secretory
      response.

PMID- 14946737
TI  - Pulmonary vasomotor responses of isolated perfused cat lungs to anoxia.

PMID- 14946738
TI  - The innervation of the cervix and cornu uteri in the rabbit.

PMID- 14946739
TI  - The mechanical analysis of the responses from the end-organs of the horizontal
      semicircular canal in the isolated elasmobranch labyrinth.

PMID- 14946740
TI  - The blood supply of the carotid body in cats, dogs and rabbits.

PMID- 14946741
TI  - The effect of stretch receptors from muscle on the discharge of motorneurons.

PMID- 14946742
TI  - The physiological cost of negative work.

PMID- 14946743
TI  - On the blood flow through rhythmically contracting muscle before and during
      release of sympathetic vasoconstrictor tone.

PMID- 14946744
TI  - PROCEEDINGS of the Physiological Society.

PMID- 14946745
TI  - Renal interstitial pressure.

PMID- 14946746
TI  - The relation between velocity of shortening and the tension-length curve of
      skeletal muscle.

PMID- 14946747
TI  - The innervation of the laryngeal mucosa of the frog.

PMID- 14946748
TI  - The effect of different iron preparations on the cells of the reticuloendothelial
      system.

PMID- 14946749
TI  - Neurohaemodynamics of acute pulmonary oedema.

PMID- 14946750
TI  - Conduction velocity of single respiratory and cardiovascular afferent fibres in
      the cervical vagus.

PMID- 14946751
TI  - Projective techniques and the theory of thinking.

PMID- 14946752
TI  - An index of pathological thinking in the Rorschach.

PMID- 14946753
TI  - The mosaic test; review.

PMID- 14946754
TI  - The case of Jay; psychological test and anamnestic data.

PMID- 14946755
TI  - Consistency and agreement in the judgment of Rorschach signs.

PMID- 14946756
TI  - A comparison of a group of hebephrenic and catatonic schizophrenics with two
      groups of normal adults by means of certain variables of the Rorschach test.

PMID- 14946757
TI  - Significance of a preponderance of human movement responses on the Rorschach in
      children below age ten.

PMID- 14946758
TI  - The detection of deviant sexual practice from performance on the Rorschach test.

PMID- 14946759
TI  - THIRTEENTH annual meeting of the society for projective techniques and Rorschach
      institute.

PMID- 14946760
TI  - FLORENTINE Hackbusch.

PMID- 14946761
TI  - The culture of psychiatric social work.

PMID- 14946762
TI  - Changing viewpoints in the casework treatment of psychotic patients.

PMID- 14946763
TI  - Education for and by volunteers--the psychiatric social worker's role.

PMID- 14946764
TI  - The psychiatric social work technician.

PMID- 14946765
TI  - PSYCHIATRIC social workers in private practice in metropolitan New York; a report
      by the private practice committee of the New York district branch.

PMID- 14946766
TI  - [Magic, myth and history].

PMID- 14946767
TI  - [Man and destiny, according to an Egyptian tale of the New Empire].

PMID- 14946768
TI  - [Observations on free drawings in children].

PMID- 14946769
TI  - [Experimental study on an abstract oral comprehension test].

PMID- 14946770
TI  - [Plato and the concept of pharmacodynamic experimentation].

PMID- 14946771
TI  - [Not Available].

PMID- 14946772
TI  - [Biological structures and explanation].

PMID- 14946773
TI  - [The role of structure in invention].

PMID- 14946774
TI  - [Linguistic structure and dualism of system in modern Greek].

PMID- 14946776
TI  - [Aurgural structures and tripartite function in the thought of ancient Rome].

PMID- 14946775
TI  - [Symbolic expressions of the tripartite religious structure at Rome].

PMID- 14946777
TI  - [Experimental research on perception of musical structures].

PMID- 14946778
TI  - [Jung's theory of archetypes].

PMID- 14946779
TI  - Further study on treatment of leucodermia with Ammi mafus linn.

PMID- 14946780
TI  - Streptomycin sensitivity of urinary and intestinal coliform bacilli in relation
      to bilharzial infection.

PMID- 14946781
TI  - The problem of inguinal hernia.

PMID- 14946782
TI  - Testicular semionoma with gastro-intestinal metastases.

PMID- 14946783
TI  - Researches on exercise.

PMID- 14946784
TI  - Use of the new antibiotics in the treatment of trachoma.

PMID- 14946785
TI  - Significance and limitations of the cancer statistics.

PMID- 14946786
TI  - The centenary of the discovery of Bilharzia.

PMID- 14946787
TI  - Hypochlorinaemia and hypochlorinuria in lobar pneumonia.

PMID- 14946788
TI  - Intra-sellar abscess simulating chromophobe adenoma.

PMID- 14946789
TI  - Mucocele of the maxillary sinus.

PMID- 14946790
TI  - Tumours of the adrenal medulla and the sympathetic nervous system, and the
      associated systemic disturbances part II (cont.).

PMID- 14946791
TI  - OBITUARY Mahmoud Bey Abdel Azim M.B., Ch. B., Cairo, D.T.M. & H., Lond.

PMID- 14946792
TI  - LIST of publications by Dr. Mahmoud Abdel Azim Bey.

PMID- 14946793
TI  - HEALTH service of the Misr Weaving and Spinning Company at Mehalla El Kobra,
      Egypt.

PMID- 14946794
TI  - Enuresis.

PMID- 14946795
TI  - Isolation of a vasodilator alkaloidal glucoside from the pollen grain of the date
      palm.

PMID- 14946796
TI  - On the incidence of bacteria in urinary tract inflammations.

PMID- 14946797
TI  - Oxycephaly and congenital talipes equino-varus in association with muscular
      dystrophy (myopathy).

PMID- 14946798
TI  - Observations on the action of anthisan on gastric secretion and motility in non
      peptic and peptic ulcer cases.

PMID- 14946799
TI  - Acute intussusception in infancy and childhood; report on 21 cases.

PMID- 14946800
TI  - Role of diabetes mellitus in the pathogenesis and treatment of diseases of teeth
      and gums (synopsis).

PMID- 14946801
TI  - Current status and therapy of amebiasis in the Arab East.

PMID- 14946802
TI  - Desoxycorticosterone in the treatment of gastric and duodenal ulcer.

PMID- 14946803
TI  - [Modern plastic surgery of the face].

PMID- 14946804
TI  - [Fifty-four cases of neuro-toxicoses of infants treated by intravenous perfusion
      of serum containing novocaine].

PMID- 14946805
TI  - Pleural effusions.

PMID- 14946806
TI  - Three cases of dissecting aneurysm.

PMID- 14946807
TI  - PHARMACIST'S handbook.

PMID- 14946808
TI  - MEDICAL certification of cause of death; instructions for physicians on use of
      international form of medical certificate of cause of death.

PMID- 14946809
TI  - INTERNATIONAL handbook on use and manufacture of insecticides to be published by
      WHO.

PMID- 14946810
TI  - Carcinoma of the bladder; surgical and pathological aspects.

PMID- 14946811
TI  - A case of adenoma of the pancreas.

PMID- 14946812
TI  - Postvaccinal (typhoid) encephalitis and its aetiology.

PMID- 14946813
TI  - A case of double uterus and double vagina.

PMID- 14946814
TI  - Anaesthesia for intrathoracic operations.

PMID- 14946815
TI  - Pentaquine in the treatment of malaria.

PMID- 14946816
TI  - Report of a case of fractured mandible and maxilla.

PMID- 14946817
TI  - Toxoplasmosis; a new disease.

PMID- 14946818
TI  - Q-fever in Egypt.

PMID- 14946819
TI  - H. M. Naval Base, Singapore. A glimpse into the hygiene and anti-malarial
      problems.

PMID- 14946820
TI  - The dental emergency.

PMID- 14946821
TI  - SHARKS.

PMID- 14946822
TI  - Treatment of nerve-gas casualties.

PMID- 14946823
TI  - Comparisons of the naval, military, R.A.F. and civil medical services with
      private practice. Part XII.

PMID- 14946824
TI  - Abdominal bloating.

PMID- 14946825
TI  - Congenital absence of the pectoralis major.

PMID- 14946826
TI  - A case of murine (flea) typhus.

PMID- 14946827
TI  - A case of canicola fever.

PMID- 14946828
TI  - SIR Arthur Gaskell.

PMID- 14946829
TI  - Medicine's tragic failure.

PMID- 14946830
TI  - Bilateral polycystic ovaries.

PMID- 14946831
TI  - The problem of nutrition in the conduct of public welfare work.

PMID- 14946832
TI  - Your Rheumatic Fever Program in action.

PMID- 14946833
TI  - Carcinoid tumors of the gastro-intestinal tract.

PMID- 14946834
TI  - PROPOSAL for socialized medicine defeated.

PMID- 14946835
TI  - The use of a group structure in speech therapy.

PMID- 14946836
TI  - A complete cleft palate program.

PMID- 14946837
TI  - SPEECH disorders and speech correction.

PMID- 14946838
TI  - Construction of one-way vision mirrors.

PMID- 14946839
TI  - An experimental approach to expectancy and anxiety in stuttering behavior.

PMID- 14946840
TI  - Parental domination in stuttering.

PMID- 14946841
TI  - Information theory. I. Information theory to 1951; a non-technical review.

PMID- 14946842
TI  - Information theory. 2. Applications of information theory to research in
      experimental phonetics.

PMID- 14946843
TI  - Information theory. 3. Applications of information theory to research in hearing.

PMID- 14946844
TI  - The influence of vowels on recognition of adjacent consonants.

PMID- 14946845
TI  - A recorded warble tone audiometer test suitable for group administration over
      loudspeakers.

PMID- 14946846
TI  - A cinefluorographic technique for the study of velopharyngeal closure.

PMID- 14946847
TI  - CLINICAL certification requirements of the American Speech and Hearing
      Association.

PMID- 14946849
TI  - Infant mortality rates in rural areas in the Gambia Protectorate.

PMID- 14946848
TI  - CODE of ethics of the American Speech and Hearing Association.

PMID- 14946850
TI  - Observations on minor degrees of anaemia in East African workers.

PMID- 14946851
TI  - A note on fluorescence microscopy in the diagnosis of leprosy.

PMID- 14946852
TI  - [Critique of the present trends and new surgical technique in the treatment of
      congenital harelip].

PMID- 14946853
TI  - [Experimental investigation on blood supply to Filatov's grafts].

PMID- 14946854
TI  - [Blood supply to Filatov's flap according to data of roentgenovasography during
      life].

PMID- 14946855
TI  - [Bronchial tamponade and drainage of sputum from the bronchial tree in
      pneumonectomy and lobectomy for pulmonary abscesses].

PMID- 14946856
TI  - [Treatment of thermal burns].

PMID- 14946857
TI  - [Effect of exercise therapy on changes of respiratory functions following
      surgery].

PMID- 14946858
TI  - [Surgical treatment of labial cancer].

PMID- 14946859
TI  - [Comparative evaluation of transpleural and transperitoneal approaches in
      surgical therapy of esophageal and cardial cancer].

PMID- 14946860
TI  - [Evaluation of the results of gastrostomy performed by Sapozhkov's method].

PMID- 14946861
TI  - [Treatment of volvulus of the sigmoid].

PMID- 14946862
TI  - [Scoliosis and its surgical therapy].

PMID- 14946863
TI  - [Study of the history of Russian surgery].

PMID- 14946864
TI  - [Correction of total defect of the nose according to author's method].

PMID- 14946865
TI  - [Struma of the carotid body].

PMID- 14946866
TI  - [Foreign bodies in the cranial region].

PMID- 14946867
TI  - [Transplantation of the testis with the seminal vesicles].

PMID- 14946868
TI  - [Case of rupture of the abdominal wall in hernia of the white line].

PMID- 14946869
TI  - [Combined method of the treatment of trophic ulcers and sluggish wounds].

PMID- 14946870
TI  - [Corrugated vascular clamps].

PMID- 14946871
TI  - [Device for connecting syringe with needle and vessel with fluid for anesthesia].

PMID- 14946872
TI  - [Modified needle-holder].

PMID- 14946873
TI  - [In memory of V. K. Fialkov].

PMID- 14946874
TI  - [In memory of I. I. Genkin].

PMID- 14946875
TI  - [Therapy of pyuria in children].

PMID- 14946876
TI  - [Dosage of penicillin and Jarisch-Herxheimer reaction in connatal lues].

PMID- 14946877
TI  - [Subsepsis, slow sepsis, sepsis].

PMID- 14946878
TI  - [Lethal poisoning of a child with zentropil].

PMID- 14946880
TI  - [Palpability of the spleen in newborn].

PMID- 14946879
TI  - [Therapy of acute summer diarrhea with formocibazol].

PMID- 14946881
TI  - [Therapy with calcium salts].

PMID- 14946882
TI  - [Report about the American pediatric literature in the year 1950].

PMID- 14946883
TI  - [Meeting of the Rhine-Westphalian Pediatricians' Association in Koln].

PMID- 14946884
TI  - [Eduard Glanzmann - to his 65 birthday].

PMID- 14946885
TI  - [Medico-prophylactic regimen, conditioned reflex sleep therapy and therapy with
      prolonged physiological sleep in the practice of therapeutic institutions of
      Ukraine].

PMID- 14946886
TI  - [Problem of expert evaluation of temporary disability].

PMID- 14946887
TI  - [Maximal pulmonary ventilation as the index of physical fitness in complex
      medical examination].

PMID- 14946888
TI  - [Clinico-bronchoscopic parallels in pulmonary cancer].

PMID- 14946889
TI  - [Treatment of pulmonary suppurations by intrapulmonary antibiotics].

PMID- 14946890
TI  - [Application of artificial pneumothorax in preoperative period].

PMID- 14946891
TI  - [Treatment of cardio-pulmonary insufficiency with neobenzinol].

PMID- 14946892
TI  - [Treatment of motor disorders following tuberculous meningitis].

PMID- 14946893
TI  - [Primary malignant tumors of the pleura].

PMID- 14946894
TI  - [Determination of renal circulation and its clinical significance].

PMID- 14946895
TI  - [Curves of arterial pressure in the diagnosis of stages of hypertension].

PMID- 14946896
TI  - [Cardio-renal syndromes in various forms of endocarditis].

PMID- 14946897
TI  - [Clinical application of streptospirit].

PMID- 14946898
TI  - [Relation between gastric polyposis and Biermer's anemia].

PMID- 14946899
TI  - [Medicinal sleep in pre- and postoperative periods].

PMID- 14946900
TI  - [Clinical aspects of congenital heart diseases].

PMID- 14946901
TI  - [Shortened P-Q interval in a child in visceral transposition].

PMID- 14946903
TI  - [Portable apparatus for the study of capillary fragility].

PMID- 14946902
TI  - [Investigation on the condition of the skin in peptic ulcer and gastric cancer].

PMID- 14946904
TI  - [Hemodynamic variations in hypertension treated with sleep therapy].

PMID- 14946905
TI  - [Hematopoiesis and peripheral blood in Botkin's disease].

PMID- 14946906
TI  - [Antitoxic liver function in rheumatism].

PMID- 14946907
TI  - [Condition of erythrocytes in erythrocytic suspension in preserved blood].

PMID- 14946908
TI  - [Studies on the synergism of certain drugs in the treatment of internal
      diseases].

PMID- 14946909
TI  - [Purpose of the schools for children with vision disorders].

PMID- 14946910
TI  - [Grueter's non-perforating cyclodiathermy].

PMID- 14946911
TI  - [Therapy of herpetic keratitides with dihydroergotamine (DHE 45)].

PMID- 14946912
TI  - [Course of a severe optochine poisoning of the retina and optic nerve in
      infancy].

PMID- 14946913
TI  - [Peristatic symptoms on the retina].

PMID- 14946914
TI  - [Endocrine cause of retinitis angiospastica; late sequelae after morbus Cushing].

PMID- 14946915
TI  - [Traumatic degeneration of the retinal vessels in juvenile hypertensive
      patients].

PMID- 14946916
TI  - [Retinal changes in sarcoidosis].

PMID- 14946917
TI  - [Argyll Robertson syndrome in suprasellar neoplasm].

PMID- 14946918
TI  - [Fibro-capillary angioma of the optic nerve].

PMID- 14946919
TI  - [Moeller's instrumental column for subjective determination of refraction with
      Walter's Visutest apparatus for determination of glasses and Schober's Idemvisus
      projecting apparatus for visual signs].

PMID- 14946920
TI  - [Horizontal demarcation line caused by a homogenous light yellow exudate in
      retroretinal macula exsudation in chorioretinitis centralis serosa].

PMID- 14946921
TI  - [Closure of a major corneal defect by diathermic coagulation].

PMID- 14946922
TI  - [Occlusion of central arteries in arteritis temporalis; case reports].

PMID- 14946923
TI  - [A case of acquired keratoglobus].

PMID- 14946924
TI  - [Retinal veins with arterial blood].

PMID- 14946925
TI  - [Healing of a case of diabetes insipidus after bilateral removal of cataract].

PMID- 14946926
TI  - [Remembering Louis Braille - on the occasion of the 100th anniversary of his
      death].

PMID- 14946927
TI  - [Vision without light and eyes; the phenomenon of Tiberius].

PMID- 14946928
TI  - [Report from the meeting of the Leipzig Ophthalmology Society].

PMID- 14946930
TI  - [41st meeting of the Ruhr District Ophthalmologists' Association].

PMID- 14946929
TI  - [Report fom the 19th meeting of the Nordwest German Ophthalmologists in Kiel].

PMID- 14946931
TI  - [40th meeting of the Ruhr District Ophthalmologists' Association].

PMID- 14946932
TI  - [Additional data on the incidence of Coxsackie virus infection in Germany].

PMID- 14946933
TI  - [The significance of aspiration biopsy of the liver for pathology and diagnosis;
      comparative studies on hepatogram, histology of the liver, clinical findings and
      liver function test].

PMID- 14946934
TI  - [Corticoid excretion in urine in cortisone therapy of chronic nephritis].

PMID- 14946935
TI  - [Corticoid excretion in urine in normal and pathological conditions; corticoides
      in urine in hypertension].

PMID- 14946936
TI  - [Corticoid excretion in urine in normal and pathological conditions; corticoid
      excretion in urine in different salt contents of food].

PMID- 14946937
TI  - [Excretion of C21-glycuronide (pregnandiolcomplex) in continuous application of
      high doses of progesterone; progesterone consumption in pregnancy].

PMID- 14946938
TI  - [Acid-base balance and regulation of respiration in chronic hypoxemia].

PMID- 14946939
TI  - [Evaluation of the diazoreaction of serum bilirubin].

PMID- 14946940
TI  - [Transportfunction of some serum-protein fractions for phosphatides; paper
      electrophoresis of protein marked P32 and S35].

PMID- 14946941
TI  - [Paper-electrophoresis of cerebrospinal fluid].

PMID- 14946942
TI  - [Therapy of lupus vulgaris with ACTH (cortiphyson)].

PMID- 14946943
TI  - [Inhibitory effects of chloramphenicol (chloromycetin) on the peristalsis of the
      small intestine in animal experiment].

PMID- 14946944
TI  - [Diminution of the antidiuretic effect of pituitary hormone by vigantol].

PMID- 14946945
TI  - [Simplification of PAH-clearance according to H. Wittkopf].

PMID- 14946946
TI  - [Clinical evaluation of TBC-antibody content of leukocytes].

PMID- 14946947
TI  - [Diabetes renalis changing into diabetes mellitus].

PMID- 14946948
TI  - [The effect of tetraethylammoniumbromide on the blood sugar].

PMID- 14946949
TI  - [Qualitative and quantitative paperchromatographical testing of various sugars in
      urine].

PMID- 14946950
TI  - [Fermentative effectors in fibrinolyses].

PMID- 14946951
TI  - [Comparison of the effect of hydergin in enteral and sublingual application].

PMID- 14946952
TI  - [Morning temperature and ovarial function].

PMID- 14946953
TI  - [Histaminemia after muscle injuries (crush syndrome); experimental studies].

PMID- 14946954
TI  - [General nonspecific metabolic changes in various endocrine disorders].

PMID- 14946955
TI  - [Cat scratch disease (maladie des griffes de chat) in Germany].

PMID- 14946956
TI  - [Dusseldorf Medical Society].

PMID- 14946957
TI  - [Typo in German: "Arztlich" correctly should begin with "A"].

PMID- 14946958
TI  - [Kiel Medical Association].

PMID- 14946959
TI  - [Marburg-on-the-Lahn Medical Association].

PMID- 14946960
TI  - [Robert Doerr in memoriam].

PMID- 14946961
TI  - [Report on 1 1/2 year of aimed prophylaxis of thrombo-emboly].

PMID- 14946962
TI  - [Electrophoretic examination of cell proteins].

PMID- 14946963
TI  - [The effect of glyco- and mucoproteins on the heat stability of serum proteins;
      the mechanism of Weltmann's coagulation reaction].

PMID- 14946964
TI  - [Ferritin, transferrin and serum-iron].

PMID- 14946965
TI  - [Microspeedtest to determine the sensitivity of germs to antibiotics].

PMID- 14946966
TI  - [Comparative studies on intermediary galactose and dextrose metabolism in healthy
      and diabetics].

PMID- 14946967
TI  - [Comparative studies on intermediary galactose and dextrose metabolism in healthy
      and in patients with liver cirrhosis].

PMID- 14946968
TI  - [The effect of vasculat on the peripheral blood circulation; clinical studies and
      therapeutic results].

PMID- 14946969
TI  - [Demonstration of latent regulation disorders by ECG under psychic stress; proof
      of heart response].

PMID- 14946970
TI  - [Elimination of stress as a pathogenic factor; stress and elimination of stress].

PMID- 14946971
TI  - [Therapy of sinu-auricular block].

PMID- 14946972
TI  - [Liberation of histamine by adrenochrome].

PMID- 14946973
TI  - [The effect of adrenochrome and histamine on the blood coagulation].

PMID- 14946974
TI  - [Studies of methylation of nor-adrenalin in vivo].

PMID- 14946975
TI  - [Effect of histamine on adrenal cortex in rats; demonstration by plasma
      reaction].

PMID- 14946976
TI  - [Production of highly concentrated alpha-sera in the diagnosis of blood groups].

PMID- 14946977
TI  - [Morphology of intoxication with Flexner-endotoxin and correlations to
      circulatory collapse].

PMID- 14946978
TI  - [Significance of endotracheal narcosis in operation of bronchial carcinoma].

PMID- 14946979
TI  - [On the occurrence of primary pure myxoma of the uterus].

PMID- 14946980
TI  - [On primary hemangioendothelioma of the stomach].

PMID- 14946981
TI  - [Esophageal carcinoma and tobacco].

PMID- 14946982
TI  - [Occupational skin cancer].

PMID- 14946983
TI  - [The control of cancer in Sweden].

PMID- 14946984
TI  - [Radiotherapy of cancer].

PMID- 14946985
TI  - [Pendulorotatory radiotherapy].

PMID- 14946986
TI  - [The history of patients with carcinoma of the stomach in relation to diagnosis
      and therapy].

PMID- 14946987
TI  - [Three years of systematic cancer cell diagnosis with Papanicolaou method in the
      I. Universitaets-Frauenklinik Wien].

PMID- 14946988
TI  - [Roentgenotherapy of morbus Bowen and multiple carcinoids].

PMID- 14946989
TI  - [Bone formation in breast carcinoma].

PMID- 14946990
TI  - [Spontaneous presence of micromyctes in the chicken embryo].

PMID- 14946992
TI  - [Austrian Society for Cancer Research and Cure].

PMID- 14946991
TI  - [The problem of amino cancers; cancer of the urinary tract].

PMID- 14946993
TI  - [International Cancer League].

PMID- 14946994
TI  - [Roentgenotherapy of the cancer of the breast].

PMID- 14946995
TI  - Polyps of the colon and rectum as forerunners of cancer.

PMID- 14946996
TI  - The use of ACTH in 10 patients with severe anogenital pruritus.

PMID- 14946997
TI  - Lobotomy case histories: ulcerative colitis and anorexia nervosa.

PMID- 14946998
TI  - Postoperative parotitis.

PMID- 14946999
TI  - Malignancy of the stomach; diagnosis by gastroscopy.

PMID- 14947000
TI  - Therapeutic trauma of the brain.

PMID- 14947001
TI  - Action of belladonna on gastric motility in man.

PMID- 14947002
TI  - On the treatment of anogenital pruritus.

PMID- 14947003
TI  - Incidence of antibiotic-resistant Staphylococci in a hospital.

PMID- 14947004
TI  - The maintenance therapy of pernicious anaemia with vitamin B12.

PMID- 14947005
TI  - Further outbreak of Bornholm disease associated with Coxsackie virus.

PMID- 14947006
TI  - Intra-articular hydrocortisone acetate in rheumatoid arthritis.

PMID- 14947007
TI  - Pancreaticogastrostomy.

PMID- 14947008
TI  - Recovery from a shot in the back of the neck.

PMID- 14947009
TI  - Bacteriophage as a factor in epidemiology and bacterial evolution; lysis of
      diphtheria Bacilli by Staphylococcal bacteriophage.

PMID- 14947010
TI  - Instrument for retrograde nailing.

PMID- 14947011
TI  - NURSES in the making.

PMID- 14947012
TI  - PHARMACOLOGY of isoniazid.

PMID- 14947013
TI  - BACTERIOPHAGE and epidemiology.

PMID- 14947014
TI  - MYXOMATOSIS and rabbits.

PMID- 14947015
TI  - FLAGELLA for spirochaetes?

PMID- 14947016
TI  - Ramon y Cajal: The first centenary of his birth.

PMID- 14947017
TI  - CLINICAL research in the United States.

PMID- 14947018
TI  - CHIEF characteristics of nerve gas with notes on first-aid treatment.

PMID- 14947019
TI  - APPEAL from the G. M. C.

PMID- 14947020
TI  - LONG-range shock.

PMID- 14947021
TI  - GEORGE Carmichael Low.

PMID- 14947022
TI  - Intranasal encephalomeningocele report of a case.

PMID- 14947023
TI  - Paracusis willisii.

PMID- 14947024
TI  - Adult tonsillectomies using pentothal sodium, curare, pontocaine and novocaine as
      the anesthetic.

PMID- 14947025
TI  - The future of otolaryngology.

PMID- 14947026
TI  - Malignant diseases of the paranasal sinuses with a case report of primary
      carcinoma of the ethmoid labyrinth complicated by nasal polyposis.

PMID- 14947027
TI  - Squamous cell carcinoma of the tympanic membrane.

PMID- 14947028
TI  - The reaction of tullio and the fenestration operation.

PMID- 14947029
TI  - Laryngectomy tube for oxygen therapy.

PMID- 14947030
TI  - [Diagnosis of celiac disease in infant].

PMID- 14947031
TI  - [Radiological study of the stomach of the premature infant].

PMID- 14947032
TI  - [Identical pictures of severe rickets with homologous spontaneous fractures in
      monozygotic twins].

PMID- 14947033
TI  - [Heine-Medin disease and phenolsulfazole].

PMID- 14947034
TI  - [Contribution to the knowledge of the pathology of the newborn infant. II.-
      Intracranial hemorrhage of the fossa occipitalis].

PMID- 14947035
TI  - [Ornithosis].

PMID- 14947036
TI  - [Toxicosis: acute alimentary disorder of encephalitis?].

PMID- 14947037
TI  - [The value of classical electrodiagnosis of stimulation in the identification of
      the non-paralytic forms of epidemic].

PMID- 14947038
TI  - [Congenital malformation of the urinary tract in the newborn].

PMID- 14947039
TI  - [Immunobiological changes in body fluids in B.C.G. vaccination; effect of age and
      vaccine dosage].

PMID- 14947040
TI  - [A case of benign infectious lymphoreticulosis (cat scratch disease)].

PMID- 14947041
TI  - [Treatment of pneumococcic meningitis with combined streptomycin and penicillin].

PMID- 14947042
TI  - [Contributions to the knowledge of the diseases of newborn infants. III.
      Diaphragmatic hernia].

PMID- 14947043
TI  - [Steroid hormones in the treatment of immaturity].

PMID- 14947044
TI  - [Isoimmunization against Rh factor].

PMID- 14947045
TI  - [Some cases of pharyngitis and gastroenteritis caused by enterotoxic
      staphylococcus in early infancy].

PMID- 14947046
TI  - [Local streptomycin therapy of superficial tubercular lymphadenitis].

PMID- 14947047
TI  - [A rare congenital cardiac malformation: total persistence of the common arterial
      trunk].

PMID- 14947048
TI  - [Specific primary mesenteric adenitis].

PMID- 14947049
TI  - [Social assistance for the illegitimate child in England].

PMID- 14947050
TI  - [Roentgen therapy in the treatment of hydrocephalus].

PMID- 14947051
TI  - [The effect of desoxycorticosterone on premature and congenitally weak infants].

PMID- 14947052
TI  - [Auxological investigation in the first two years of life].

PMID- 14947053
TI  - [Absence of anti-brucella action, in vitro, of hydrazide of isonicotinic acid].

PMID- 14947054
TI  - [Bonnevie Ulrich syndrome in newborn; pathogenetic theory of blebs].

PMID- 14947055
TI  - [An atypical case of tetany associated with cataract in a two-month-old infant].

PMID- 14947056
TI  - [Pathology of the newborn infant. IV. Fibrinopurulent peritonitis caused by
      perforation of cecal ulcers].

PMID- 14947057
TI  - [Pneumothorax complicated by a painful vasomotor syndrome of the face following a
      Jacobaeus operation].

PMID- 14947058
TI  - [Comparative bacteriological examination of the sputum, gastric lavage, and
      bronchial secretions of tuberculotics].

PMID- 14947059
TI  - [Thoracoplasty and apicolysis].

PMID- 14947060
TI  - [Anesthesia in thoracic and pulmonary surgery].

PMID- 14947061
TI  - [History of Canadian physicians].

PMID- 14947062
TI  - [The treatment of insanity a hundred years ago].

PMID- 14947063
TI  - [Examination of the colons by the double contrast method].

PMID- 14947064
TI  - [Hysteria and cerebral tumor].

PMID- 14947065
TI  - [Curable psychoses of the aged].

PMID- 14947066
TI  - [Liver dysfunction in chronic alcoholics; obviated by the function tests and
      treatment by lipotropic factors].

PMID- 14947067
TI  - [The basis of BCG].

PMID- 14947068
TI  - [Postoperative thromboembolism].

PMID- 14947069
TI  - [History of the Faculty of Medicine of Laval].

PMID- 14947070
TI  - [Cosmopolitism and objectivism in the medical science and in the public health].

PMID- 14947071
TI  - [Present state of leukemia].

PMID- 14947072
TI  - [Anaphylactoid purpura in surgical treatment of tuberculosis].

PMID- 14947073
TI  - [Case of ectopia cordis pectoralis].

PMID- 14947074
TI  - [Blunt abdominal wounds in children].

PMID- 14947075
TI  - [Tuberculous chancre].

PMID- 14947076
TI  - [Placenta accreta as a complication of pregnancy].

PMID- 14947077
TI  - [Evaluation of electrocardiographic changes in acute rheumatic heart disease].

PMID- 14947078
TI  - [Attempt to transplant rat tumor BS-1 into the testes in rats].

PMID- 14947079
TI  - [Bacteremia of odontogenous origin].

PMID- 14947080
TI  - [Clinical aspects of infant mortality].

PMID- 14947081
TI  - [Occupational poisoning with tricresylphosphate].

PMID- 14947082
TI  - [Free skin transplantation in extensive defects].

PMID- 14947083
TI  - [Radiotherapy of pulmonary cancer].

PMID- 14947084
TI  - [Isonicotinic acid hydrazide in the treatment of tuberculosis].

PMID- 14947085
TI  - [Research on the resistance of Koch's bacillus to isonicotinyl hydrazide].

PMID- 14947086
TI  - [Research on a substance with tuberculin activity in the urine of patients
      treated with isonicotinyl hydrazide].

PMID- 14947087
TI  - [Antituberculous property of isonicotinic acid hydrazide].

PMID- 14947088
TI  - [Laboratory data on the first results of isonicotinic acid hydrazide in the
      therapy of tuberculosis].

PMID- 14947089
TI  - [First clinical observations on the therapeutic application of isonicotinic acid
      hydrazide in human tuberculosis].

PMID- 14947090
TI  - [First clinical and therapeutic observations on isonicotinic acid hydrazide].

PMID- 14947091
TI  - [Modifications of tuberculous allergic skin reactions in isonicotinic acid
      hydrazide therapy].

PMID- 14947092
TI  - [States of susceptibility and resistance in tuberculosis].

PMID- 14947093
TI  - [Perfusions of para-aminosalicylic acid solutions in the treatment of pulmonary
      and meningeal tuberculosis].

PMID- 14947094
TI  - [Results of two years activity of the dispensary section of the municipal jail].

PMID- 14947095
TI  - [Work of the sanatorium in occupational rehabilitation of tuberculotics].

PMID- 14947096
TI  - [The vast program for 1952 of provincial antituberculosis organizations].

PMID- 14947097
TI  - [Professor Lucien Cornil].

PMID- 14947098
TI  - [Cancers due to occupations; their modes of prevention].

PMID- 14947099
TI  - [American biologists seek the key to cancer by studying the biochemical mechanism
      of growth].

PMID- 14947100
TI  - [Inaugural address of Paul Ribeyre].

PMID- 14947102
TI  - [The good and bad cancers].

PMID- 14947101
TI  - [Several aspects of the battle against cancer].

PMID- 14947103
TI  - [On the pretended treatment of cancer].

PMID- 14947104
TI  - [The great fear of our century].

PMID- 14947105
TI  - [Importance of the battle against cancer].

PMID- 14947106
TI  - [The reason for our propaganda].

PMID- 14947107
TI  - [The role of the laboratory in the detection of cancer].

PMID- 14947108
TI  - [Medical treatment of cancer].

PMID- 14947109
TI  - [What I think of the growth of anticancerous centers].

PMID- 14947110
TI  - [The efficiency of the National Week of Defense Against Cancer].

PMID- 14947112
TI  - [Treatment of so-called "central" pains].

PMID- 14947111
TI  - [Hypertension with, or caused by, suprarenal tuberculosis].

PMID- 14947113
TI  - [Pathogenesis of varicose veins in pregnancy].

PMID- 14947114
TI  - [Diagnosis and treatment of compression of the common bile duct caused by chronic
      pancreatitis].

PMID- 14947115
TI  - [Surgical aspects of silico-tuberculosis].

PMID- 14947116
TI  - [Current therapy of diffuse periurethral phlegmon; former "infiltration of
      urine"].

PMID- 14947117
TI  - [Primary vertebral sarcomas; three cases].

PMID- 14947118
TI  - [A case of conservative surgery for bilateral coxalgia].

PMID- 14947119
TI  - [Very large cyst of the ovary; multi-stage operation].

PMID- 14947120
TI  - [Surgical indications in intracavitary uterine fibromas].

PMID- 14947121
TI  - [Possibilities of conservative surgery in the therapy of intracavitary uterine
      myomas].

PMID- 14947122
TI  - [Exposed dislocation of the elbow with rupture of the humeral artery].

PMID- 14947123
TI  - [Large resection for osteosarcoma with immediate acrylic endoprosthesis].

PMID- 14947124
TI  - [Value of removal of ganglions of neck in remote results of therapy of cancer of
      the lower lip].

PMID- 14947125
TI  - [Vertebral grafts and industrial accidents].

PMID- 14947126
TI  - [A case of invagination of the appendix on a cecal tumor with argentaffin cells].

PMID- 14947127
TI  - [Nervous disorders of arm after thoracoplasty treated with scalenectomy].

PMID- 14947128
TI  - [Constitution of rheumatic aortic endocarditis during and in spite of intensive
      and prolonged A C T H therapy].

PMID- 14947129
TI  - [Multiple sub-cutaneous tubercular gummas complicating a primary infection].

PMID- 14947130
TI  - [Bouillaud's illness in a food allergy syndrome].

PMID- 14947131
TI  - [Serious intrapleural hemorrhages after pneumothorax insufflations].

PMID- 14947132
TI  - [Experimental notes on a muscle relaxant: 9.295 C].

PMID- 14947133
TI  - [Surgical treatment of the transposition of arteries].

PMID- 14947134
TI  - [Inert caverns in total pneumothorax; statistical and therapeutic study].

PMID- 14947135
TI  - [Remarkable tolerance of dihydrostreptomycin (from hospital statistics)..].

PMID- 14947136
TI  - [Cochlear accidents attributed to dihydrostreptomycin; a report of total deafness
      following 25 grams of D.H.S. administered intrapleurally].

PMID- 14947137
TI  - [Gastric cancer in young person with acute hemolytic anemia].

PMID- 14947138
TI  - [Current biological procedures in the diagnosis and post-operative supervision of
      a malignant adrenal cortex with endocrine symptomatology].

PMID- 14947139
TI  - [Rectal amebiasis, tumorous form].

PMID- 14947140
TI  - [Current biological procedures in the diagnosis and post-operative supervision of
      a malignant adrenal cortex with endocrine symptomatology].

PMID- 14947141
TI  - [Citrate of soda in vascular diseases; use of the Courbin method].

PMID- 14947142
TI  - [Favorable effect of terramycin on bilibronchial fistulas].

PMID- 14947143
TI  - [Delayed silicosis].

PMID- 14947144
TI  - [Infectious mononucleosis similar to cholecystitis].

PMID- 14947145
TI  - [Tubercular round focus caused by conglomerate nodules].

PMID- 14947146
TI  - [Dorsal vertebral metastases as a warning of bronchial cancer].

PMID- 14947147
TI  - [Value of radiology in the diagnosis of allergic diseases of the small
      intestine].

PMID- 14947148
TI  - [Indication for segmental resection for tuberculosis].

PMID- 14947149
TI  - [The value of radiology in the diagnosis of allergic affections of the small
      intestine].

PMID- 14947150
TI  - [Distribution of diptheria cases among vaccinated and non-vaccinated in Lyon].

PMID- 14947151
TI  - [Myocardial infarct in 26-year-old athlete].

PMID- 14947152
TI  - [Short angina attacks, on strict digestive schedule, with total absence of crises
      of exertion (Gallavardin type); electrocardiographic data].

PMID- 14947153
TI  - [Recent law making antituberculosis vaccination with BCG compulsory].

PMID- 14947154
TI  - [Branches of the anterior tibial artery immediately after its passage above the
      interosseous membrane].

PMID- 14947155
TI  - [Bleeding mammary glands; method of locating the lesion by mammography and
      injection of methylene blue in the milk duct].

PMID- 14947156
TI  - [Facial neuralgia of possible hormonal origin].

PMID- 14947157
TI  - [A case of acardius in twin pregnancy].

PMID- 14947158
TI  - [Histochemical examination of the endometrium].

PMID- 14947159
TI  - [Migration of the ovum].

PMID- 14947160
TI  - [Implantation of the ureter into the sigmoid].

PMID- 14947161
TI  - [Results of vitamin K treatment in prophylaxis of hypoprothrombinemia of the
      newborn].

PMID- 14947162
TI  - [Pregnancy associated with congenital total atrio-ventricular block].

PMID- 14947163
TI  - [Progress in treatment of abnormal fetal presentation].

PMID- 14947164
TI  - [Intestinal fistulas following abdominal surgery].

PMID- 14947165
TI  - [Treatment of adnexitis by Filatov's biogenic stimulation].

PMID- 14947166
TI  - [Sarcoma following recurrent myoma].

PMID- 14947167
TI  - [Proliferation of uterine cancer following radiotherapy].

PMID- 14947168
TI  - [Purulent meningitis with eclampsia].

PMID- 14947169
TI  - [Pregnancy at term following surgery of ovarian abscess].

PMID- 14947170
TI  - [Myasthenia gravis and pregnancy].

PMID- 14947171
TI  - [Pelvimetry of the narrow pelvis].

PMID- 14947172
TI  - [Suppurative abdominal cysts].

PMID- 14947173
TI  - [Diagnostic value of tubal insufflation].

PMID- 14947174
TI  - [Experiments in the treatment of male sterility].

PMID- 14947175
TI  - [Significance of curettage in presence of adnexitis].

PMID- 14947176
TI  - [Surgical results in the treatment of chronic persistent adnexitis].

PMID- 14947177
TI  - [Uterine sarcoma in pregnancy].

PMID- 14947178
TI  - [Balneotherapy of chronic adnexitis].

PMID- 14947179
TI  - [Clinical and histological diagnosis of uterine sarcoma].

PMID- 14947180
TI  - [The role of antispasmodics in alleviating labor pain].

PMID- 14947181
TI  - [Critical observations regarding the diagnosis of prolonged pregnancy].

PMID- 14947182
TI  - [Uterine cancer after prolonged use of estrogen ointment].

PMID- 14947183
TI  - [Addison's disease and pregnancy].

PMID- 14947184
TI  - [A rare case of toxemia causing diagnostic difficulties].

PMID- 14947185
TI  - [Uterine lipoma of rare size].

PMID- 14947186
TI  - [Spontaneous rupture of a cystocarcinoma ovarii].

PMID- 14947187
TI  - [Postoperative radiographic findings following gastrointestinal
      thoracolaparatomy].

PMID- 14947188
TI  - [Hypertrophic pyloric stenosis in adults].

PMID- 14947189
TI  - [Significance of osteo-atrophy in the early diagnosis and therapy of
      osteoarticular tuberculosis].

PMID- 14947190
TI  - [Neurotrophic bone deformations].

PMID- 14947192
TI  - [Rules for protection of physicians and other personnel in roentgenographic
      establishments].

PMID- 14947191
TI  - [Radium therapy of carcinoma in the pre-epiglottic vallecula].

PMID- 14947193
TI  - [Dr. Erno Schiffer].

PMID- 14947194
TI  - [Dr. Ferenc Russo].

PMID- 14947195
TI  - [Technique and application of bronchography].

PMID- 14947196
TI  - [A case of morbus Boeck-Besnier-Schaumann].

PMID- 14947197
TI  - [Urography and tomography of perirenal insufflation].

PMID- 14947198
TI  - [Submucosal hematomas of frontal sinuses].

PMID- 14947199
TI  - [New apparatus for protection against gamma-radiation].

PMID- 14947200
TI  - [Combined therapy of osteoarticular tuberculosis].

PMID- 14947201
TI  - [Therapeutic effect of volatile oil containing azulene in experimentally induced
      radiation injuries].

PMID- 14947202
TI  - [Negative histological findings in carcinoma of the buccal cavity].

PMID- 14947203
TI  - [Surgical treatment of spondylitis tuberculosa involving the spinal marrow].

PMID- 14947204
TI  - [Effect of active movement on the lymph circulation of contracting tendons].

PMID- 14947205
TI  - [Experimental gastro-esophageal anastomosis].

PMID- 14947206
TI  - [Significance of the mobilization of mesenterium in antethoracic esophagoplasty].

PMID- 14947207
TI  - [A healed case of bilateral tension pneumothorax after removal of thymus tumor].

PMID- 14947208
TI  - [Cervical hemangioma with acute compression of cord].

PMID- 14947209
TI  - [Large parotid stone in child].

PMID- 14947210
TI  - [Pavlov's teaching and its urological significance; summarized report].

PMID- 14947211
TI  - [Experiences with the Filatov-therapy in urology].

PMID- 14947212
TI  - [Histological examination of the immediate area surrounding vesical tumors].

PMID- 14947213
TI  - [Clinical findings and therapy of prostatic lithiasis].

PMID- 14947214
TI  - [Experimental studies on the pathogenesis of ozena].

PMID- 14947215
TI  - [The specific treatment of ozaena].

PMID- 14947216
TI  - [Studies on the virulence of the bacterial flora of the oral cavity].

PMID- 14947217
TI  - [The hearing after conservative radical operations; an experimental analysis of
      the significance of the retained tympanum].

PMID- 14947218
TI  - [A new method for the removal of rhinoliths; four case reports].

PMID- 14947219
TI  - [Nasal vestibular cyst].

PMID- 14947220
TI  - [The chemical signs of arsenical intoxication].

PMID- 14947221
TI  - [Transmission of rabies to Tanger by the sewer rat].

PMID- 14947222
TI  - [Treatment of vertigo and tinnitus with octyl alcohol].

PMID- 14947223
TI  - [Vitality of microbes].

PMID- 14947224
TI  - [Note on ACTH and cortisone in practice].

PMID- 14947225
TI  - [On the diagnosis of coronary angina pectoris].

PMID- 14947226
TI  - [The Hargraeves-Blanc method in the treatment of amebiasis of Morocco].

PMID- 14947227
TI  - [Streptomycin therapy of female gonorrhea; advantages in Morocco].

PMID- 14947228
TI  - [Complications of symphysiotomy].

PMID- 14947229
TI  - [Some data on the early laboratory-diagnosis of whooping cough].

PMID- 14947230
TI  - [Human infection by the Newcastle virus].

PMID- 14947231
TI  - [The compared value of different tuberculins in demonstrating allergy in cattle].

PMID- 14947232
TI  - [Prostatism and onions].

PMID- 14947233
TI  - [The necessity to reorganize leprosy control in French West Africa].

PMID- 14947234
TI  - [A case of bilateral osteochondromatosis of the knees].

PMID- 14947235
TI  - [A case of tuberculous peritonitis treated by thiosemicarbazone].

PMID- 14947236
TI  - [Transitory ocular paralysis following streptomycin therapy].

PMID- 14947237
TI  - [Myoclonus, early manifestation of lung cancer].

PMID- 14947238
TI  - [Late syndrome of chronic occlusion after appendectomy; Noble's operation].

PMID- 14947239
TI  - [Doctor Georges Blanc Director of the Pasteur Institute of Morocco member of the
      Academy of Medicine].

PMID- 14947240
TI  - [The Military Hospital of Casablanca renamed Hopital Jean Vial].

PMID- 14947241
TI  - [Account of a pilgrimage to Mecca].

PMID- 14947242
TI  - [Congenital syphilis, generalities].

PMID- 14947243
TI  - [Hormonal physiopathology of gestation and congenital syphilis].

PMID- 14947244
TI  - [Etiology of spontaneous abortion outside of syphilis].

PMID- 14947245
TI  - [Cutaneo-mucous manifestations of congenital syphilis].

PMID- 14947246
TI  - [Nervous manifestations of congenital syphilis].

PMID- 14947247
TI  - [The osseous alterations of congenital syphilis].

PMID- 14947248
TI  - [Some reflections on heredo-ocular syphilis].

PMID- 14947249
TI  - [Heredo-syphilis in cardiology].

PMID- 14947250
TI  - [Reflections on neurological and neurosurgical observations of congenital or
      acquired dystrophies].

PMID- 14947251
TI  - [The place of heredo-syphilis in infant neuro-psychiatry].

PMID- 14947252
TI  - [First Moroccan statistics on congenital syphilis].

PMID- 14947253
TI  - [How to set up a team work study of congenital syphilis in Morocco].

PMID- 14947254
TI  - [Behavior of the choriomeningitis virus in the pregnant rabbit].

PMID- 14947255
TI  - [On three compulsory reactions in the serology of syphilis].

PMID- 14947256
TI  - [For the pasteurization of milk and its control].

PMID- 14947257
TI  - [The presence of morphologically identical inclusions in trachoma cells and on
      the mucous of the cervix uteri of 50% of the women trachomatously examined].

PMID- 14947258
TI  - [Fatal acute meningitis of the newborn].

PMID- 14947259
TI  - [Reflections on the surgical treatment for volvulus of the sigmoid colon].

PMID- 14947261
TI  - [Enterogenic rheumatism].

PMID- 14947260
TI  - [On the treatment of epitheliomas of the floor of the mouth].

PMID- 14947262
TI  - [Hyaluronidase, its clinical indications].

PMID- 14947263
TI  - [Emotional diabetes, role of emotions in diabetes].

PMID- 14947264
TI  - [Twisting of the small intestines around the mesenteric pedicle].

PMID- 14947265
TI  - [Bronchopneumonia and diaphragmatic hernia in a baby of five months of age].

PMID- 14947266
TI  - [Contribution to the study of a recent epidemic disease; medical vulgarization].

PMID- 14947267
TI  - [Modern therapeutics].

PMID- 14947268
TI  - [Modern neurology].

PMID- 14947269
TI  - [Laws of the occurrence of eosinophilia in the parasitosis animals].

PMID- 14947270
TI  - [General adaptation syndrome].

PMID- 14947271
TI  - [Current treatment of surrenal insufficiency].

PMID- 14947272
TI  - [On three observations of hemochromatosis].

PMID- 14947273
TI  - [Hyperparathyroidism and the kidney].

PMID- 14947274
TI  - [Hormonal inclusions in gynecology].

PMID- 14947275
TI  - [Hepato-gonadal syndromes].

PMID- 14947276
TI  - [Edematous exophthalmos in its relation with hyperthyroidism].

PMID- 14947277
TI  - [Modern concepts of Myxedema].

PMID- 14947278
TI  - [A case of Addison's disease treated in Morocco].

PMID- 14947279
TI  - [Considerations on the problem of obesity, therapeutic experiences].

PMID- 14947280
TI  - [Traumatic and emotional diabetes].

PMID- 14947281
TI  - [Hormonal factors in water metabolism, pathological deviations].

PMID- 14947282
TI  - [Control of threatened abortion by hormonal urinalysis].

PMID- 14947283
TI  - [Spontaneous abortion, etiology and prophylactic hormonal therapy].

PMID- 14947284
TI  - [On the discovery of the glands of internal secretion].

PMID- 14947285
TI  - [Reflections on the conditions of activity of the hormones].

PMID- 14947286
TI  - [Progress in the pharmacology of diabetes mellitus].

PMID- 14947287
TI  - [Natural estrogens of alimentary origin in domestic animals].

PMID- 14947288
TI  - [Biological diagnosis of pregnancy and determination of gonadotropic hormones
      with the Moroccan bull frogs].

PMID- 14947289
TI  - [Clinical significance of follicle stimulating hormone determination].

PMID- 14947290
TI  - [Laboratory examinations during treatments by ACTH and cortisone].

PMID- 14947291
TI  - [On the synthesis of insulin in Morocco during the war].

PMID- 14947292
TI  - [Voluntary apnea test; research concerning its value in the selection of flying
      personnel].

PMID- 14947293
TI  - [Apnea test following forced expiration, control by blood oxymetry (Millikan's
      method)].

PMID- 14947294
TI  - [Value of examination of the vegetative nervous system as an aid to Flack's
      test].

PMID- 14947295
TI  - [Effect of thiamine hydrochloride on alcoholic intoxication in monkeys exposed to
      simulated altitude].

PMID- 14947296
TI  - [Aerial war and medical services].

PMID- 14947297
TI  - [Plea for a timid man].

PMID- 14947298
TI  - [Diagnosis of prolonged fever].

PMID- 14947299
TI  - [Use of histamine in psychiatry].

PMID- 14947300
TI  - [The liver and estrogen pathology].

PMID- 14947301
TI  - [Genital hemorrhages occurring after menopause; statistics from Maternity
      hospital in Berne 1919-1949].

PMID- 14947302
TI  - [The danger of inefficient pneumothorax and its radiological aspects].

PMID- 14947303
TI  - [Discussion on teaching and professional development of medical personnel].

PMID- 14947304
TI  - [Can hold psychosurgery for legitimate if ...].

PMID- 14947305
TI  - [Psychosurgery and juridical problems].

PMID- 14947307
TI  - [Lobotomy is a palliative procedure].

PMID- 14947306
TI  - [Pro and con of prefrontal leucotomy].

PMID- 14947308
TI  - [Leucotomy causes definite changes of the nervous system].

PMID- 14947309
TI  - [Functional treatment of paradontolysis].

PMID- 14947310
TI  - [Painless drilling; new technique and apparatus].

PMID- 14947311
TI  - Therapy of poliomyelitis.

PMID- 14947312
TI  - Cerebral hemodynamics in cerebral arteriovenous vascular anomalies; report of two
      cases.

PMID- 14947313
TI  - The use of whole blood.

PMID- 14947314
TI  - The use and abuse of some new drugs.

PMID- 14947315
TI  - BLIND babies.

PMID- 14947316
TI  - Podiatry.

PMID- 14947317
TI  - WILLIAM Raymond Moulden, M.D. (1877-1952).

PMID- 14947318
TI  - J. WARD Mankin, M.D. (1874-1952).

PMID- 14947319
TI  - FREDERICK Young Donn, Phar. D., Ph. C., M.D. (1885-1952).

PMID- 14947320
TI  - Ben David Chinn, Ph.B., Ph.D., M.D. (1904-1952).

PMID- 14947321
TI  - OLIN West, M.D. (1874-1952).

PMID- 14947322
TI  - GEORGE Walter McCoy, M.D., F.A.C.P. (1876-1952).

PMID- 14947323
TI  - JOSEPH W. Mountin, M.D. (1891-1952).

PMID- 14947324
TI  - CHARLES Sumner Robbins, M.D. (1876-1952).

PMID- 14947325
TI  - MEDICAL Society of the District of Columbia 1952-1953.

PMID- 14947326
TI  - The nature of clinical syndromes.

PMID- 14947327
TI  - The nephrotic syndrome; pathogenesis, diagnosis and treatment.

PMID- 14947328
TI  - The kidney of gout, a clinical entity.

PMID- 14947329
TI  - Recent developments in the therapy of edema.

PMID- 14947330
TI  - Circulatory consequences of blood kinetic energy with special reference to the
      kidney.

PMID- 14947331
TI  - Radioiodine in the diagnosis of thyroid disorders.

PMID- 14947332
TI  - The prevention of coronary thrombosis.

PMID- 14947333
TI  - Atherosclerosis; a preventable disease?

PMID- 14947334
TI  - The management of high blood pressure.

PMID- 14947335
TI  - Therapeutic use of quinidine.

PMID- 14947336
TI  - The physiology of the lesser circulation as altered by acquired and congenital
      heart disease.

PMID- 14947337
TI  - The diagnosis and management of hemorrhagic disorders.

PMID- 14947338
TI  - The effects of ACTH and cortisone in diseases of the digestive system.

PMID- 14947339
TI  - Antibacterial agents in gastrointestinal disease.

PMID- 14947341
TI  - Systemic lupus erythematosus.

PMID- 14947340
TI  - Large gastric ulcers, not demonstrable at roentgenologic examination.

PMID- 14947343
TI  - Neurosyphilis; pathogenesis, classification and present day treatment.

PMID- 14947342
TI  - Current concepts in the management of atopic dermatitis.

PMID- 14947344
TI  - The significance of the birth of a large baby.

PMID- 14947345
TI  - Clinical studies of magnesium metabolism.

PMID- 14947346
TI  - Nontropical sprue complicated by generalized amyloidosis; observations on the
      exchange of nitrogen, calcium and phosphorus.

PMID- 14947348
TI  - The management of the acute phase of poliomyelitis.

PMID- 14947347
TI  - Diagnosis and clinical features of poliomyelitis.

PMID- 14947349
TI  - The prevention of crippling following poliomyelitis.

PMID- 14947350
TI  - Public health aspects of poliomyelitis in Victoria.

PMID- 14947351
TI  - The poliomyelitis epidemic of 1950-1951 in the Newcastle area.

PMID- 14947352
TI  - Tracheotomy in bulbar poliomyelitis.

PMID- 14947353
TI  - Poliomyelitis and atmospheric conditions in certain Australian cities.

PMID- 14947354
TI  - Respiratory insufficiency in poliomyelitis.

PMID- 14947355
TI  - A case of poliomyelitis with facial paralysis following a dental procedure.

PMID- 14947356
TI  - The aetiology of anaemia.

PMID- 14947357
TI  - Chronic non-leukemic myelosis.

PMID- 14947358
TI  - Retrosternal goiter.

PMID- 14947359
TI  - DISEASES notified in each State and Territory of Australia for the week ended
      June 7, 1952.

PMID- 14947360
TI  - Modern investigation and treatment of infertility.

PMID- 14947361
TI  - The dangers of social adjustment.

PMID- 14947362
TI  - Bone grafting in the treatment of fractures.

PMID- 14947364
TI  - Obesity.

PMID- 14947363
TI  - Precocious general development of normal type.

PMID- 14947365
TI  - PEPTIC ulcer.

PMID- 14947366
TI  - Anticoagulant therapy in myocardial infarction.

PMID- 14947367
TI  - Coarctation of the aorta.

PMID- 14947368
TI  - Hoarseness and cancer of the larynx.

PMID- 14947369
TI  - Rethinking old problems in urology.

PMID- 14947370
TI  - Dislocation of the hip with fracture of the posterior acetabular rim.

PMID- 14947372
TI  - CATHETERIZATION of the male urethra.

PMID- 14947371
TI  - Traumatic retroperitoneal hemorrhage.

PMID- 14947373
TI  - COLLEGE again.

PMID- 14947374
TI  - ARTIFICIAL respiration.

PMID- 14947375
TI  - Athletics: some physiological and pathological questions.

PMID- 14947376
TI  - HAEMOCHROMATOSIS.

PMID- 14947377
TI  - ANTICONVULSANT drugs in epilepsy.

PMID- 14947378
TI  - HYDRATION treatment of eclampsia.

PMID- 14947379
TI  - The housing problem in France.

PMID- 14947380
TI  - EOSINOPHIL granulocyte.

PMID- 14947381
TI  - MEDICAL Practitioners Union thirty third annual general meeting.

PMID- 14947382
TI  - CORONARY in the armchair.

PMID- 14947383
TI  - WORSE than before.

PMID- 14947384
TI  - The management of the rheumatoid arthritic.

PMID- 14947385
TI  - Vitamin B12.

PMID- 14947386
TI  - Aberdeen and the ninety-six per cent.

PMID- 14947387
TI  - NEGLECT of patients with cancer.

PMID- 14947388
TI  - INDUSTRIAL medical research.

PMID- 14947389
TI  - COMMONWEALTH health and tuberculosis conference.

PMID- 14947390
TI  - [Citrovorum factor].

PMID- 14947391
TI  - [Transitory aphasias].

PMID- 14947392
TI  - [Acute suppurative strumitis; study on thyostrumitis].

PMID- 14947393
TI  - [Some considerations on the biochemistry of blood iron; review].

PMID- 14947394
TI  - [Considerations on thirty two interventions for strangulated hernia of the
      inguinocrural region].

PMID- 14947395
TI  - [Case of osteogenesis imperfecta].

PMID- 14947396
TI  - [Vitamin T therapy].

PMID- 14947397
TI  - [Primary tuberculosis in children].

PMID- 14947398
TI  - [Serology of syphilis; fundamentals, procedures, technic and interpretation].

PMID- 14947399
TI  - [Surrealism and psychopathology].

PMID- 14947400
TI  - [Catheterization of the left ventricle in man].

PMID- 14947401
TI  - [Comparative study on vaginal smears and urinary sediments].

PMID- 14947402
TI  - [New mitotic toxin; sabine].

PMID- 14947404
TI  - [Therapeutic possibilities of levulose].

PMID- 14947403
TI  - [Isonicotinic acid hydrazide in the treatment of tuberculosis].

PMID- 14947405
TI  - [Viruses as causative agents of cancer].

PMID- 14947406
TI  - [Effect of folic acid in macrocytic anemia in white rats].

PMID- 14947407
TI  - [Prolonged development of certain cardial cancers].

PMID- 14947408
TI  - [Cranial injuries in private practice; review and prognosis of 80 cases].

PMID- 14947409
TI  - [Bundle of His block].

PMID- 14947410
TI  - [Meteorology and climatology in health and in disease].

PMID- 14947411
TI  - [Subacute strumitis and thyroid abscess].

PMID- 14947412
TI  - [Epidemiological study on an outbreak of poliomyelitis in the Province of Sevilla
      in 1950].

PMID- 14947413
TI  - [Relation between minimal and maximal arterial pressure].

PMID- 14947414
TI  - [Kerr's symballophone].

PMID- 14947415
TI  - [Hypophyseal exomphalos].

PMID- 14947416
TI  - [Critique of a new surgical technic].

PMID- 14947417
TI  - [Intra-aortic transfusion of blood and graplasmoid].

PMID- 14947418
TI  - [Electrodehydration and electrolytic depilation].

PMID- 14947419
TI  - [Plan for a possible regulation of medical services in the field according to
      present aspects of military medicine].

PMID- 14947420
TI  - [Kidney diseases and bone diseases; kidneys and bone metabolism].

PMID- 14947421
TI  - [Notes on cortisone and ACTH and their importance in military medicine].

PMID- 14947422
TI  - [Maximal passive rights].

PMID- 14947423
TI  - [Clinical note; rabies].

PMID- 14947424
TI  - [Clinical surgical note; bilateral pulmonary lobectomy for tuberculoma].

PMID- 14947425
TI  - [Santiago Ramon y Cajal, a military surgeon].

PMID- 14947426
TI  - [Evaluation of the theory of neurons].

PMID- 14947427
TI  - [The live matter and the dead matter in the theory of neurons].

PMID- 14947428
TI  - [Cajal as a scientist].

PMID- 14947429
TI  - [Isonicotinic acid hydrazide as a new drug in the treatment of tuberculosis].

PMID- 14947431
TI  - [Clinical note; case of Wolff-Parkinson-White syndrome].

PMID- 14947430
TI  - [Leukocytes level in a soldier].

PMID- 14947432
TI  - [Clinical surgical note; study on total permanent acoustic paralysis].

PMID- 14947433
TI  - [Plan for a possible regulation of medical services in the field according to
      present concepts of military medicine].

PMID- 14947434
TI  - [Treatment of thoracic war wounds].

PMID- 14947435
TI  - [Treatment of renal tuberculosis].

PMID- 14947436
TI  - [Clinical note; bronchial foreign body].

PMID- 14947437
TI  - [Surgical clinical note; post-laparotomy desmoid tumors].

PMID- 14947438
TI  - [Clinical note; leprosy].

PMID- 14947439
TI  - [Elements of neurological semeiology. I. Movement].

PMID- 14947440
TI  - [A rare form of meningitis].

PMID- 14947441
TI  - [Enterococcic endocarditis; treatment of one case].

PMID- 14947442
TI  - [Combined antibiotics].

PMID- 14947443
TI  - [Electroencephalographic diagnosis of cerebral tumors].

PMID- 14947444
TI  - [So-called painful tumor of the chondro-costal joint].

PMID- 14947445
TI  - [Blood proteins; significance in universal diagnosis].

PMID- 14947446
TI  - [New drugs in the treatment of tuberculosis; isonicotinic acid hydrazides].

PMID- 14947447
TI  - [Ferran and the epidemic of cholera in Valencia in 1885].

PMID- 14947448
TI  - [Babinski's sign].

PMID- 14947449
TI  - [Painless labor].

PMID- 14947450
TI  - [Hypophyseal cretinism; case of insufficiency of the pituitary thyrotropic
      factor].

PMID- 14947451
TI  - [Case of tetanus].

PMID- 14947452
TI  - [Treatment of Sydenham's chorea].

PMID- 14947453
TI  - [Classical mechanics and biological mechanics].

PMID- 14947454
TI  - [Diameter and volume of erythrocytes, spherocytic index, index of saturation in
      lead anemia].

PMID- 14947455
TI  - [Studies of the blood picture in silicosis].

PMID- 14947456
TI  - [Experimental studies on intoxication with caprolattame].

PMID- 14947457
TI  - [Biological determination of gonads-stimulating hormones of the anterior
      pituitary in urine in silicosis].

PMID- 14947458
TI  - [Condition of 463 silicotic patients treated in 1943-47 at the Clinica del Lavoro
      in Milano].

PMID- 14947459
TI  - [Present clinical contributions to occupational eczema in hydrogen peroxide
      industry].

PMID- 14947460
TI  - [Effect of respiration through dead-space on oxygen metabolism during work].

PMID- 14947461
TI  - [Carbon monoxide in the blood].

PMID- 14947462
TI  - The present state of ophthalmology.

PMID- 14947463
TI  - Ocular therapeutics.

PMID- 14947464
TI  - Keratoplasty.

PMID- 14947465
TI  - The nature of exophthalmos.

PMID- 14947466
TI  - Illustration in ophthalmology.

PMID- 14947467
TI  - Spectacles and their origin.

PMID- 14947468
TI  - [Treatment of hepatocellular jaundice with desoxycorticosterone acetate].

PMID- 14947469
TI  - [Radioisotopes].

PMID- 14947470
TI  - [Surgical treatment of intraocular cysticercosis].

PMID- 14947471
TI  - [Water-borne epidemic of typhoid fever in Drvaru in 1949-50].

PMID- 14947472
TI  - [Pathogenic factors of hypertension].

PMID- 14947473
TI  - [Treatment of a case of poisoning with stovarsol with BAL].

PMID- 14947474
TI  - [Etiology of diseases of the optic nerve of unknown origin with radiological
      examination of the optic canals].

PMID- 14947475
TI  - [Experience with aureomycin in trachoma].

PMID- 14947476
TI  - [Epidemiology of diphtheria in the postwar time].

PMID- 14947477
TI  - [Acute phase of chronically relapsing cholecystitis; indications for operation].

PMID- 14947478
TI  - [Critical comments on the electrocardiogram in relaxation, standing and during
      work].

PMID- 14947479
TI  - [Disturbances of water metabolism in latent hepatopathy].

PMID- 14947480
TI  - [Experimental and clinical investigations on the therapy of chronic polyarthritis
      with lipoid- and serum fractions of retroplacental blood].

PMID- 14947481
TI  - [Clinical investigations of broncholytic activity of aludrin in healthy people
      and asthmatics; special consideration of registering thoracography].

PMID- 14947482
TI  - [Therapy of actinomycosis with sulfonamides and antibiotics].

PMID- 14947483
TI  - [My 301, a new muscle relaxant].

PMID- 14947485
TI  - [Therapy of fermentative disorders].

PMID- 14947484
TI  - [Therapy of ascending polyradiculoneuritis with pyrifer].

PMID- 14947486
TI  - [Electrodermatogram of Head's zones in abdominal diseases].

PMID- 14947487
TI  - [Therapy of chronic muscle- and joint diseases with formic and silicic acids].

PMID- 14947488
TI  - [Therapeutic use of glutamic acid].

PMID- 14947489
TI  - [Local therapeutic use of digitalis in asthenopia].

PMID- 14947490
TI  - [Dental and jaw diseases in newborn].

PMID- 14947491
TI  - [Spiritual folk medicine in old religious books].

PMID- 14947492
TI  - [1st International Allergy Congress].

PMID- 14947493
TI  - [Old and new comments on hypertrophy of prostate].

PMID- 14947494
TI  - [Comment on modern blood vessel surgery with continuation of blood flow].

PMID- 14947495
TI  - [Present evaluation of the central analgesic polamidon].

PMID- 14947496
TI  - [The question of gastric mucosal prolapse].

PMID- 14947497
TI  - [Animal experiments and autoexperiments on the muscle relaxant My 301].

PMID- 14947498
TI  - [Stability of thrombokinase solutions; simplification of prothrombin
      determination].

PMID- 14947499
TI  - [Importance of x-ray examination in swallowed foreign bodies].

PMID- 14947500
TI  - [Myo-melcain in differential diagnosis and in neural therapeutic anesthesia].

PMID- 14947501
TI  - [Practical value of determination of bladder- and sphincter tonus].

PMID- 14947502
TI  - [Octinum D in the development of synthetic spasmolytics].

PMID- 14947503
TI  - [Sleep as biological and anthropological problem].

PMID- 14947504
TI  - [Lucas Johann Boer].

PMID- 14947505
TI  - [Retrospect of the 1951 Therapy Week].

PMID- 14947506
TI  - [Effect of antistine on skin allergy and immunity tests].

PMID- 14947507
TI  - [The study of lice feeding on guinea pigs].

PMID- 14947508
TI  - [New tuberculosis vaccine. I. Results of vaccination of youth].

PMID- 14947509
TI  - [Differentiation of acid fast bacilli with the aid of chemotherapeutics].

PMID- 14947510
TI  - [Action mechanism of antibiotics; differences of behavior of typhoid bacillus
      cell fractions obtained from streptomycin-sensitive and resistant strains].

PMID- 14947511
TI  - [Protective effect of formaldehyde on penicillin in nonsterile aqueous solutions
      and filtrates of Penicillium cultures].

PMID- 14947512
TI  - [Origin of antibodies agglutinating Clostridia in healthy human and animal
      serum].

PMID- 14947513
TI  - [Modification of Hisrt hemagglutination inhibition reaction, excluding
      nonspecific inhibitors].

PMID- 14947514
TI  - [Agglutination and complement-fixation of Leptospira, in relation to the method
      of culture].

PMID- 14947515
TI  - [Typing of typhoid bacilli from the Poznan district in the years of 1948-50 by
      means of standard bacteriophages of Crain and Felix].

PMID- 14947516
TI  - [Occurrence of Salmonella bacillus in rodents in the city and region of Kielce].

PMID- 14947517
TI  - [Bacterial flora in nonspecific urethritis in men].

PMID- 14947518
TI  - [Botulin toxin type A].

PMID- 14947519
TI  - [Adsorption of gram-negative endotoxic symplexes on the surface of erythrocytes;
      role of polysaccharide fractions].

PMID- 14947520
TI  - [Adsorption of gram-negative endotoxic symplexes on the surface of erythrocytes;
      utilization of erythrocytes-fixation in the investigation and elution of protein
      fractions of endotoxic symplex].

PMID- 14947521
TI  - [Variability of polysaccharides in hemolytic streptococci; analysis by the
      hemagglutination and precipitation method].

PMID- 14947522
TI  - [Effect of Salmonella typhosa fractions on viral hemagglutination; gradient of
      inhibition].

PMID- 14947523
TI  - [Immunologic study of disintegration processes in tuberculosis].

PMID- 14947524
TI  - [Chemical and biological properties of purified tuberculin proteins of
      saprophytic mycobacteria].

PMID- 14947525
TI  - [Inhibiting action of Pseudomonas aeruginosa on the growth of Aspergillus
      fumigatus].

PMID- 14947526
TI  - [Anti-Vi agglutinins as the index of infection].

PMID- 14947527
TI  - [Evaluation of differentiation of strains of Salmonella typhosa with typhoid anti
      Vi bacteriophages in epidemiological studies].

PMID- 14947528
TI  - [Staining variations of acid-fast bacilli cultures].

PMID- 14947529
TI  - [Observations on the role of rats as the epidemiological factor in infectious
      jaundice].

PMID- 14947530
TI  - [Hypopotassemia in reflex intestinal obstruction following ileostomy and Noble's
      operation].

PMID- 14947531
TI  - [Vertebral grafting].

PMID- 14947532
TI  - [Three cases of Noble's operation].

PMID- 14947533
TI  - [Paraduodenal hernia and diverticulum of the small intestine].

PMID- 14947534
TI  - [Post-operative and posttraumatic pulmonary atelectasis].

PMID- 14947535
TI  - [Fluxion reflexes of pulmonary interstitial tissue, classification of
      interstitial reflexes].

PMID- 14947536
TI  - [Methods of measurement of blood volume; studies on 10 cases of hemorrhagic
      gastroduodenal ulcer].

PMID- 14947537
TI  - [Two cases of sudden death following retro-sternal esophagoplasty with colon].

PMID- 14947538
TI  - [Nutrition in burns].

PMID- 14947539
TI  - [Measurement of blood volume in hemorrhagic peptic ulcer].

PMID- 14947540
TI  - [Two cases of sudden death following retrosternal esophagoplasty with colon].

PMID- 14947541
TI  - [Essay with anabolic therapy].

PMID- 14947542
TI  - [Method of pedicle grafting in pretibial skin loss].

PMID- 14947543
TI  - [Transperitoneal arthrodesis in the treatment of spondylolysis and
      spondylolisthesis of the fifth lumbar vertebra].

PMID- 14947544
TI  - [In memory of the ex-president of the Academy Georges Labey; presidential
      address].

PMID- 14947545
TI  - [Address of the president for 1952].

PMID- 14947546
TI  - [Studies on dysuria of noncervical origin in young boys; seven cases of dysuria
      due to seminal calculi].

PMID- 14947547
TI  - [Surgical treatment of a case of permanent hypertension caused by unilateral
      hydronephrosis and hypertensive paroxystic crisis due to homolateral adrenal
      hematoma].

PMID- 14947548
TI  - [Duodeno-pancreatectomy].

PMID- 14947549
TI  - [Four cases of pancreatic surgery; one case of generalized lithogenous
      pancreatitis].

PMID- 14947550
TI  - [Case of right segmental hepatectomy].

PMID- 14947551
TI  - [Discussion on the first case of segmental hepatectomy].

PMID- 14947552
TI  - [Two cases of lumbar hernia].

PMID- 14947553
TI  - [Hartman's method in the treatment of prolapse of perineal artificial anus].

PMID- 14947554
TI  - [Nailing of fractures of the lower third of the femur and of the tibia by the low
      approach; Introduction of a nail for tibial and condylar malleoli].

PMID- 14947555
TI  - [Reconstruction of the destroyed thumb by annular or fifth finger pollicization].

PMID- 14947556
TI  - [Case of tibial impacted fracture].

PMID- 14947557
TI  - [Ovarian grafts into the labia majora; prolonged success and evolutive
      complications].

PMID- 14947558
TI  - [Plane oblique osteotomy in correction of deformities of the extremities].

PMID- 14947559
TI  - [In memory of Henry Billet].

PMID- 14947560
TI  - [New observation on esophagoplasty with the right colon].

PMID- 14947561
TI  - [Osteotomy of the extremities].

PMID- 14947562
TI  - [Vertebral grafting].

PMID- 14947563
TI  - [Fragment injuries of the pregnant uterus].

PMID- 14947564
TI  - [Grafting of preserved human aorta in the treatment of coarctation of the aorta].

PMID- 14947565
TI  - [Observation on successful surgery of two cases of aortic coarctation].

PMID- 14947566
TI  - [Results and indications for spleno-renal anastomosis; operation of 53 cases of
      portal hypertension].

PMID- 14947567
TI  - [Use of hexamethonium in pulmonary resections].

PMID- 14947568
TI  - [Possibility of draining cardiac cavities by hexamethonium and simultaneous
      clamping of venae cavae; attempted direct intracardiac surgery, experimental
      study].

PMID- 14947569
TI  - [Controlled hypotension in operative orthopedics and in surgical repairs].

PMID- 14947570
TI  - [400 lumbar infiltrations associated with anticoagulant therapy without accident
      in phlebitis].

PMID- 14947571
TI  - [Treatment of essential coccygodynia by sacral rugination].

PMID- 14947572
TI  - [Fractures of the inferior third of the tibial diaphysis].

PMID- 14947573
TI  - [Use of muscle relaxants in neurosurgery; advantages of the method in excision of
      cerebral tumors].

PMID- 14947574
TI  - [Observations on 47 cases of anesthesia with controlled hypotension].

PMID- 14947575
TI  - [Diminished bleeding by the method of controlled hypotension in pelvic surgery].

PMID- 14947576
TI  - [Murphy's operation in perforations in typhus].

PMID- 14947577
TI  - [Results of cytodiagnosis of broncho-pulmonary, gastric, renal, prostatic,
      vesical, and serous malignant tumors].

PMID- 14947578
TI  - [Anatomical, clinical, histological, and biochemical study on the action of
      thyroxin, desoxycorticosterone and cortisone on the development of experimental
      fractures in dogs].

PMID- 14947579
TI  - [Regeneration of the intima following surgery of arterial obstruction in man].

PMID- 14947580
TI  - [Resorption of arterial embolus by tromexan].

PMID- 14947581
TI  - [Calcinosis of the leg consecutive to gunshot wound of 33 years duration].

PMID- 14947582
TI  - [In memory of Bierens de Haan (1867-1951), foreign member].

PMID- 14947583
TI  - [Immediate surgical treatment of 14 cases of perforated duodenal ulcer].

PMID- 14947584
TI  - [Treatment of duodenal fistula by local application of fresh placenta].

PMID- 14947585
TI  - [Treatment of cancers of the cervix uteri].

PMID- 14947586
TI  - [Per-cardiac reanimation].

PMID- 14947587
TI  - [Chronic leg ulcers of varicose origin; therapy and physiopathology].

PMID- 14947588
TI  - [Role of the kidneys in surgical diseases].

PMID- 14947589
TI  - [Duodenopancreatectomy].

PMID- 14947590
TI  - The security of discipline.

PMID- 14947591
TI  - An evaluation of recent adolescent drug addiction.

PMID- 14947592
TI  - Mental health and the maladjusted child.

PMID- 14947593
TI  - The mental hygiene of adolescence in the Anglo-American culture.

PMID- 14947594
TI  - Community efforts in mental hygiene.

PMID- 14947595
TI  - Home care of the aged mentally ill.

PMID- 14947596
TI  - An experimental approach to mental health in the program of a children's
      hospital.

PMID- 14947597
TI  - Relating the state mental-hygiene program to the local community.

PMID- 14947598
TI  - Problems of retirement.

PMID- 14947599
TI  - Toward a more productive concept of mental health.

PMID- 14947600
TI  - A tribute to Clifford W. Beers from the Fourth International Congress on Mental
      Health.

PMID- 14947601
TI  - Current bibliography.

PMID- 14947602
TI  - Metabolic and clinical effects of corticotropin (ACTH) on essential glycogenosis
      (von Gierke's disease).

PMID- 14947603
TI  - Serum lipids and lipoproteins in diabetic glomerulosclerosis.

PMID- 14947604
TI  - Diabetes detection survey among male physicians.

PMID- 14947605
TI  - Metabolic and clinical effects of different regimens in patients with chronic
      liver disease.

PMID- 14947606
TI  - Blood sugar and food intake in rats with lesions of the anterior hypothalamus.

PMID- 14947607
TI  - The role of the reticuloendothelial system in vitamin A and cholesterol
      metabolism.

PMID- 14947609
TI  - GOUT.

PMID- 14947608
TI  - The effect of pituitary growth hormone on the insulin tolerance of the
      adrenalectomized dog.

PMID- 14947610
TI  - [An apparatus for increasing the illuminated field in low magnifications].

PMID- 14947611
TI  - [Modifications of the blood cells in vitro].

PMID- 14947612
TI  - [Low magnification photography].

PMID- 14947613
TI  - [The examination of human excreta in criminologic detection].

PMID- 14947614
TI  - [Description of a simple apparatus for time-lapse microphotography].

PMID- 14947615
TI  - [Electron microscopy of ciliate organelles].

PMID- 14947616
TI  - [Cicatricial stenosis of the esophagus caused by caustic burn;
      esophagogastrostomy by intrathoracic route; recovery].

PMID- 14947617
TI  - [Biliodigestive anastomosis].

PMID- 14947618
TI  - [Experimental resection and restoration of the thoracic trachea and bronchial
      bifurcation with temporary polythene prostheses].

PMID- 14947619
TI  - [Experimental resection of the cervical and thoracic trachea and its restoration
      by fresh and preserved homologous grafts].

PMID- 14947620
TI  - [A synthetic substitute for plasma: polyvinylpyrrolidone (periston, subtosan)].

PMID- 14947621
TI  - [Alcoholization of the meso-appendix in appendectomy].

PMID- 14947622
TI  - [Local penicillin therapy of pyogenic infections].

PMID- 14947623
TI  - [Second National Congress of Surgery of Madrid].

PMID- 14947624
TI  - [First International Medico-Scientific Film Festival].

PMID- 14947625
TI  - [Functional disturbances in gastric resection].

PMID- 14947627
TI  - [Etiopathogenesis and rational therapy in surgery].

PMID- 14947626
TI  - [Body fluid changes caused by curare].

PMID- 14947628
TI  - [Action of the spreading factor (hyaluronidase) on the reabsorption of
      hemoperitoneum and hemarthros].

PMID- 14947629
TI  - [A case of lipoma with large ossification].

PMID- 14947630
TI  - [Biliary ileus following duodenal-cholecystic fistula].

PMID- 14947631
TI  - [Transkeletal phlebography of the lower limbs].

PMID- 14947632
TI  - [Tests and clinical results with a new synthetic antiemetic].

PMID- 14947633
TI  - [Laminectomy].

PMID- 14947634
TI  - [Remote results of antropyloric resections in gastroenteroanastomized].

PMID- 14947635
TI  - [Extra-articular cicatricial lockjaw].

PMID- 14947636
TI  - [Use of complete bipedunculated flaps of whole skin in the treatment of large
      post-operative hernias].

PMID- 14947637
TI  - [The heparinoid "Thrombocid": results of experimental and clinical research].

PMID- 14947638
TI  - [Action of curare and other anesthetic drugs administered through the carotid in
      the cranial direction].

PMID- 14947639
TI  - [Rare angiographic examination in the living subject after ligation of the
      inferior vena cava].

PMID- 14947640
TI  - [Post-operative function of the sphincter in surgery for rectal cancer].

PMID- 14947641
TI  - [Capillary hamartoma of the tongue].

PMID- 14947642
TI  - [Transplantations of fixed and preserved tissues].

PMID- 14947643
TI  - [Tenth annual congress of the American Academy of Dermatology and Syphilology
      (Chicago, 8-13 December 1951)..].

PMID- 14947644
TI  - [Mechanism of action of dihydroergotamine in symmetrical sympathetic syndromes of
      the lower extremities in subjects with osteoarticular lesions of the sacrolumbar
      spine].

PMID- 14947645
TI  - [Eighty cases of leprosy studied from the point of view of the new South American
      classification].

PMID- 14947646
TI  - [Results of combined therapy in the general treatment of cutaneous tuberculosis].

PMID- 14947647
TI  - [Persistent serological reactions: pathogenesis and therapy; preventive report].

PMID- 14947648
TI  - [Estimation of the exit dose and its practical importance in superficial x-ray
      therapy in some dermatoses localized in the hands and extremities].

PMID- 14947649
TI  - [Tests of intracutaneous therapy in lupus erythematosus].

PMID- 14947650
TI  - [Cardiolipin antigens adapted to the Spicca flocculation reaction].

PMID- 14947651
TI  - [Dermatoses of tubercular and non-tubercular origin in tubercular subjects].

PMID- 14947652
TI  - [A case of so-called benign inoculation lymphoreticulosis or cat scratch
      disease].

PMID- 14947653
TI  - [Histological changes in the skin following irradiation of roentgen cautery].

PMID- 14947654
TI  - [Recurrences of cutaneous epitheliomas: seriousness, causes and treatment].

PMID- 14947655
TI  - [Culture of gonococcus by the new Debray-Le Minor method].

PMID- 14947656
TI  - [Non-gonococcal urethritis; first results of search for Chlamydozoon
      oculogenitale and pleuropneumonia-like organisms].

PMID- 14947657
TI  - [Ion variations of the blood in eczema].

PMID- 14947658
TI  - [Electrophoretic analysis of blood proteins in skin diseases].

PMID- 14947659
TI  - [Tissue antigens and autohistotherapy in the treatment of some cases of
      psoriasis].

PMID- 14947660
TI  - [Tests of the velocity of reabsorption of fluids injected into mucous membrane
      and skin].

PMID- 14947661
TI  - [New routes to the regulation of functional insufficiencies in the obstetric and
      gynecological field].

PMID- 14947662
TI  - [Electrophrenic respiration].

PMID- 14947663
TI  - [Electrical neuromuscular excitation by rectangular waves in the application of
      electrophrenic respiration].

PMID- 14947664
TI  - [Tests of electrophrenic respiration by means of rectangular-wave electrical
      impulses].

PMID- 14947665
TI  - [Use of the pneumoamnion in the induction of labor in cases of intrauterine death
      of the fetus].

PMID- 14947666
TI  - [Pharmacodynamic behavior of lung extracts after aerosol introduction of
      posthypophysial hormones (in diapulmonary posthypophysial therapy)].

PMID- 14947667
TI  - [Urinary elimination of pregnandiol in pregnancy at term; diurnal rhythm].

PMID- 14947668
TI  - [Eclampsia and solar activity].

PMID- 14947669
TI  - [Extraction of fetus with extractor].

PMID- 14947670
TI  - [Critical evaluation and classification of the factors determining blood protein
      disorders in some nephrotic-edematous forms of gestosis].

PMID- 14947671
TI  - [Hyperfolliculinic syndrome].

PMID- 14947673
TI  - [Atelectatic syndrome of the middle lobe].

PMID- 14947672
TI  - [New anti-tuberculosis drugs].

PMID- 14947674
TI  - [Contribution of bioptic findings to a histopathological classification of
      diffuse gastropathies].

PMID- 14947675
TI  - [The importance of psychic factors in the genesis of cardiospasm].

PMID- 14947676
TI  - [Streptokinase and streptodornase, fibrinolytic enzymes].

PMID- 14947677
TI  - [Establishment of the Ministry of Hygiene and Public Health].

PMID- 14947678
TI  - [Inspector General for child health].

PMID- 14947679
TI  - [Deaf-mutism and genetics].

PMID- 14947680
TI  - [Two cases of alimentary toxicosis].

PMID- 14947681
TI  - [Electrocardiographic changes in two grave cases of uremia].

PMID- 14947682
TI  - [A case of dermatomyositis].

PMID- 14947683
TI  - [New anti-tuberculosis drugs].

PMID- 14947684
TI  - [Unforeseen complications in the law concerning hospital competitive
      examinations].

PMID- 14947685
TI  - [Long range competitive examinations].

PMID- 14947686
TI  - [Grafts and transplantations in the history of medicine].

PMID- 14947688
TI  - [The thoracic "cripple"..].

PMID- 14947687
TI  - [The value of intestinal radiological signs in sprue].

PMID- 14947689
TI  - [Essential thrombophilia (Nygaard and Brown's disease)].

PMID- 14947690
TI  - [Medicine in "I Promessi Sposi"..].

PMID- 14947691
TI  - [Struggle against a social menace; bilharzia].

PMID- 14947692
TI  - [Combined ultrasonics and histamines].

PMID- 14947693
TI  - [Effect of vitamin B12 on alterations induced by methylthiouracil in the adrenal
      and thyroid glands and on physical development (experimental research)..].

PMID- 14947694
TI  - [Parapneumothoracic pleurisy; encouraging therapeutic success with "P factor"..].

PMID- 14947696
TI  - [First International Medico-Scientific Film Festival].

PMID- 14947695
TI  - [Nutrition in tuberculosis].

PMID- 14947697
TI  - [Three hundred and fifth electroencephalographic examinations of infants and
      children].

PMID- 14947698
TI  - [Podophyllin and its active principles in cancer therapy].

PMID- 14947699
TI  - [The nitrate esters of polyalcohols in some cardiovascular diseases].

PMID- 14947700
TI  - [Psychic factors and digestive and metabolic diseases].

PMID- 14947701
TI  - [Contribution of the plant world to medicine].

PMID- 14947702
TI  - [Diagnostic radioactive iodine].

PMID- 14947703
TI  - [Michele Servetus (1509-1553) and the lesser circulation].

PMID- 14947704
TI  - [Transfer of the University of Ferrara to Rovigo].

PMID- 14947705
TI  - [Current biological problems and surgical action].

PMID- 14947706
TI  - [Electrocardiographic findings and heart diseases in the students of the schools
      of Genoa].

PMID- 14947707
TI  - [Use of p-aminosalicylate of 1-phenyl-1-pyridyl (2')-3-dimethylaminopropane
      (Avil) in skin diseases].

PMID- 14947708
TI  - [New anatomical-physiological premises concerning pulmonary exeresis].

PMID- 14947709
TI  - [Pathogenesis of Mediterranean anemias and classification of hemolytic anemias].

PMID- 14947710
TI  - [Medical journalism reviewed by a precursor].

PMID- 14947711
TI  - [Crenology and crenotherapy through the centuries].

PMID- 14947712
TI  - [Anti-allergic therapy with combined calcium, magnesium and rutin].

PMID- 14947713
TI  - [Prognostic data on 140 cases of myocardial infarct after recovery from the acute
      attack].

PMID- 14947714
TI  - [New histological criteria for the diagnosis of chronic appendicitis].

PMID- 14947715
TI  - [Atypic forms of generalized carcinosis].

PMID- 14947716
TI  - [Indications for exeresis in pulmonary tuberculosis and the anatomical and
      functional condition induced by the operation].

PMID- 14947717
TI  - [Medicine through the ages].

PMID- 14947718
TI  - [Antonio Cardarelli].

PMID- 14947719
TI  - [Juvenile delinquency and its prevention].

PMID- 14947720
TI  - [Acute cholecystitis and early surgical treatment].

PMID- 14947721
TI  - [Perlingual testosterone in geriatric therapy].

PMID- 14947722
TI  - [Selection of antibiotics; the disk method in pneumophthisiology].

PMID- 14947723
TI  - [Proposal for a new direction in tumor research].

PMID- 14947724
TI  - [Protein growth factors in liver extract].

PMID- 14947725
TI  - [Hematological damage in gastric resection].

PMID- 14947726
TI  - [Clinical significance and diagnostic value of cutireactions with food
      allergens].

PMID- 14947727
TI  - [Remote results of the ligation of the inferior cava in the treatment of cardiac
      insufficiency].

PMID- 14947728
TI  - [Combined suicide and homicide].

PMID- 14947729
TI  - [Biomicroscopic study of lenticular changes resulting from prolonged chilling].

PMID- 14947730
TI  - [Detection of sperm with acid phosphatase tests].

PMID- 14947731
TI  - [Boldrini's ink tests for the detection of forgery].

PMID- 14947732
TI  - [Third International Congress on Social Welfare].

PMID- 14947733
TI  - [Value and limitations of graphometrics in the examination of written documents].

PMID- 14947734
TI  - [Humification of cadavers].

PMID- 14947735
TI  - [Medicolegal diagnosis of inflammatory exudates in stains by means of extraction
      and demonstration of Menkin's leukotaxine].

PMID- 14947736
TI  - [Improvement of chemical tests to detect carbon monoxide in blood].

PMID- 14947737
TI  - [Significance of the "small peripheral hearts" in death following prolonged
      decubitus].

PMID- 14947738
TI  - [The paraffin glove, technic and results].

PMID- 14947739
TI  - [Apiol poisoning].

PMID- 14947740
TI  - [Forensic aspects of attempted suicide in relation to health insurance].

PMID- 14947741
TI  - [Effect of streptomycin on post-mortem changes].

PMID- 14947742
TI  - [Forensic aspects of withdrawal in the treatment of alcoholism].

PMID- 14947743
TI  - [New problems concerning viability and hemolytic disease of the newborn].

PMID- 14947744
TI  - [A case of vita apnoica extrauterina].

PMID- 14947745
TI  - [Limitations of application of psychosurgery and the rights of human
      personality].

PMID- 14947746
TI  - [Significance of the former condition in forensic evaluation of permanent
      impairment of the masticatory apparatus].

PMID- 14947747
TI  - [Reversible psychogenic paralysis interpreted as loss of an extremity].

PMID- 14947748
TI  - [Conflicts and difficulties in the treatment of initial tuberculosis in the field
      of social welfare].

PMID- 14947749
TI  - [Cellular changes occurring within a few hours after death].

PMID- 14947750
TI  - [Lipotrophic and hepato-protective factors in experimental selenium, thallium and
      bismuth poisoning].

PMID- 14947751
TI  - [Experimental research on proteolytic autolysis in viscera preserved by
      refrigeration].

PMID- 14947752
TI  - [Histologic changes in refrigerated viscera].

PMID- 14947753
TI  - [Selye syndrome and numbness].

PMID- 14947754
TI  - [Prof. Ugo Lombroso].

PMID- 14947755
TI  - [Rupture of the heart by contusion].

PMID- 14947756
TI  - [Characteristics of ink; analytical research in the field of criminology. Note
      II.-Chromatographic analysis].

PMID- 14947757
TI  - [Autopsy finding on hernia sac and location of the site of contusive injury
      causing intestinal rupture; criticism of article 41 of the existing penal code].

PMID- 14947758
TI  - [Possible equalization of percental aliquots of compensation and extent of
      damage, for calculation of payments in compulsory insurance against industrial
      work accidents and occupational diseases].

PMID- 14947759
TI  - [Anatomo-histopathological experimental research on metol poisoning (p
      methylaminophenol sulfate)].

PMID- 14947760
TI  - [Histochemical methods and phenomena of residual life].

PMID- 14947761
TI  - [Research on B antigen].

PMID- 14947762
TI  - [Development of Rh factor].

PMID- 14947763
TI  - [Distribution of blood groups and Rh factor in population of Padua].

PMID- 14947764
TI  - [Elimination of the isoantigen property].

PMID- 14947765
TI  - [Criticism of the so-called criminogenic diencephaloendocrinosis].

PMID- 14947766
TI  - [Narcoanalysis and its applications in penal procedure in Italy].

PMID- 14947767
TI  - [Fatal industrial accidents caused by exposure to cold].

PMID- 14947768
TI  - [Experimental granuloma caused by beryllium].

PMID- 14947769
TI  - [Effect of the nervous system on cadaveric rigidity].

PMID- 14947770
TI  - [Narcoanalysis in insurance medicine; advantages and legality].

PMID- 14947771
TI  - [Concept of urgency in hospital admission].

PMID- 14947772
TI  - [The heredity of taste blindness].

PMID- 14947773
TI  - [The effect of sulfamides and antibiotics on the process of putrefaction].

PMID- 14947774
TI  - [Spectrophotometric characteristics of blood regenerated "in vitro" after carbon
      monoxide saturation].

PMID- 14947775
TI  - [Articles 5, 6 and 7 of law No. 138 of 11 January 1943 and collective contracts].

PMID- 14947776
TI  - [Medicolegal interpretation of intracranial digital impressions].

PMID- 14947777
TI  - [Stark and Stivel phenomenon].

PMID- 14947778
TI  - [Liver tissue changes in experimental streptomycin poisoning].

PMID- 14947779
TI  - [Contusive cranioencephalic injuries and variations of the blood picture;
      experimental research].

PMID- 14947780
TI  - [Transformative processes in cadavers enclosed in zinc case].

PMID- 14947781
TI  - [The concept of cure of mental diseases in relation to judgment of fitness for
      gainful employment].

PMID- 14947782
TI  - [Service-connected suicide in military legal medicine].

PMID- 14947783
TI  - [Vaccination complications considered as industrial accident].

PMID- 14947784
TI  - [Cervicobrachial syndrome caused by cervical rib attributed to industrial
      accident].

PMID- 14947785
TI  - [Determination of the egg content of egg noodles].

PMID- 14947786
TI  - [Colorimetric determination of malonic acid in wines and must cider].

PMID- 14947787
TI  - [Formation of diacetyl in moist bread].

PMID- 14947788
TI  - [General method of calculation of linear chemical processes; application to the
      colorimetric determination of cholesterol by the lumetron].

PMID- 14947789
TI  - [Sensitivity of the mucic acid reaction of Kent and Tollens].

PMID- 14947790
TI  - [Preparation of soluble starch].

PMID- 14947791
TI  - [Report from the 63. Annual Meeting of the Swiss Association for Analytic and
      Applied Chemistry].

PMID- 14947792
TI  - [Methods of microchemistry].

PMID- 14947793
TI  - [Investigation on different liposoluble coloring agents by chromatography on an
      aluminum disc].

PMID- 14947794
TI  - [Fixation of chromatograms on aluminum discs].

PMID- 14947795
TI  - [Micro carbohydrate determination without lead peroxide].

PMID- 14947796
TI  - [Phase contrast microscopy].

PMID- 14947797
TI  - [The distase content of malt extracts].

PMID- 14947799
TI  - The treatment of peripheral arteriosclerosis.

PMID- 14947798
TI  - [Ozone determination in drinking water].

PMID- 14947800
TI  - [Scientific session of September 20, 1951].

PMID- 14947801
TI  - [Endotracheal inhalation anesthesia, a possibility to avoid surgical trauma in
      oto-rhino-laryngology].

PMID- 14947802
TI  - [Experiences with endotracheal anesthesia in big laryngeal, nose and throat
      surgery].

PMID- 14947803
TI  - [Granuloma pediculatum (pyogenicum, teleangiectaticum) in otorhinolaryngology].

PMID- 14947804
TI  - [Our experiences with endotracheal anesthesia].

PMID- 14947805
TI  - [Anesthesia in endoscopy].

PMID- 14947806
TI  - [Modern methods of anesthesia in otorhinolaryngology].

PMID- 14947807
TI  - [Local anesthesia in inflammatory tissue].

PMID- 14947808
TI  - [Novocaine-privin-penicillin solution in local anesthesia in
      otorhinolaryngology].

PMID- 14947809
TI  - [Frontal lobe infiltration for anesthetic purposes in otorhinolaryngology].

PMID- 14947810
TI  - [Therapeutic anesthesia in otorhinolaryngology].

PMID- 14947811
TI  - [Postoperative anesthesia in tonsillectomy].

PMID- 14947812
TI  - [Therapy of glosso-pharyngeal neuralgia].

PMID- 14947813
TI  - [Control of bleeding and postoperative anesthesia].

PMID- 14947814
TI  - [Use of the skin of the auditory meatus in plastic surgery in radical
      mastoidectomy].

PMID- 14947815
TI  - [Therapy of acute and chronic diseases of the throat with anesthesia].

PMID- 14947816
TI  - [Experiences with the peripheral compression of the trigeminal nerve].

PMID- 14947817
TI  - [Pain arising from paranasal sinuses].

PMID- 14947818
TI  - [Therapy of otalgia].

PMID- 14947819
TI  - [Pathogenesis of headache in extracranial diseases].

PMID- 14947820
TI  - [Histamine and nitroglycerine test in headache].

PMID- 14947822
TI  - [Investigations on partition of the intensity of pure sounds].

PMID- 14947821
TI  - [Surgery of narrow glottis in paresis of recurrent nerve].

PMID- 14947823
TI  - [Austrian Oto-Laryngology Society].

PMID- 14947824
TI  - Contribution to the incidence of multiple sclerosis among Jews in Israel.

PMID- 14947825
TI  - [Magic and technology in delusions].

PMID- 14947826
TI  - [Puncture of the cisterna pontis through the foramen ovale].

PMID- 14947827
TI  - [Dermatomyositis with cerebral lesions (encephalodermatomyositis)].

PMID- 14947828
TI  - [Occupational cramps; chronoaxometric study on occupational cramps].

PMID- 14947829
TI  - [Psychological characteristics of habitual criminals jailed under Swiss criminal
      law].

PMID- 14947830
TI  - [Relation of the reflex of Barraquer (grapp reflex of the foot) to the spasticity
      of the flexor muscles of the toes].

PMID- 14947831
TI  - [Psychiatry and civilization].

PMID- 14947832
TI  - Bilateral destruction of the hippocampus (cornu ammonis) in a case of dementia.

PMID- 14947833
TI  - [Subcortical changes in Picks disease in comparison to Huntington's chorea].

PMID- 14947834
TI  - [Functional deficits after occipital lobectomy].

PMID- 14947835
TI  - [Pathologic anatomy of diabetes insipidus].

PMID- 14947836
TI  - Food poisoning due to the consumption of shellfish.

PMID- 14947837
TI  - Bacteriological studies on cooked shellfish.

PMID- 14947838
TI  - Ophthalmia neonatorum; a review of the prophylactic methods at present in use.

PMID- 14947839
TI  - NOTIFICATION of infectious disease in England and Wales, May, 1952.

PMID- 14947840
TI  - Staphylococcus aureus in a slaughterhouse.

PMID- 14947841
TI  - Electron-microscopic evidence on the structure of spirochaetes.

PMID- 14947842
TI  - Orientation of the polypeptide chains in crystals of acid insulin sulphate.

PMID- 14947843
TI  - A new after-effect of x-rays on dilute aqueous suspensions of bacteriophage.

PMID- 14947844
TI  - Effect of ionizing radiation on protein denaturation.

PMID- 14947845
TI  - O-aminophenol in experimental tuberculosis.

PMID- 14947846
TI  - Isolation of methoxy- and 2:6-dimethoxy-p-benzoquinone from fermented wheat germ.

PMID- 14947847
TI  - Uptake of plasma amino-acids by the perfused isolated cow's udder.

PMID- 14947848
TI  - Purification of commercial samples of cestrone.

PMID- 14947849
TI  - An unknown amino-acid occurring in the rock lobster (Jasus lalandii).

PMID- 14947850
TI  - A crystalline constituent from myogen of carp muscles.

PMID- 14947851
TI  - Cytochrome c and in vitro formation of bile pigments.

PMID- 14947852
TI  - Interaction of dextran and fibrinogen.

PMID- 14947853
TI  - Evoked single cortical unit activity in the primary cortical receiving areas.

PMID- 14947854
TI  - Effect of high environmental temperature on the oxygen consumption of
      thyroidectomized, hypophysectomized and methylthiouracil-treated rats and the
      related action of thyroxine.

PMID- 14947855
TI  - A new method of age determination for mammals.

PMID- 14947856
TI  - Some electrical differences between healthy and virus-infected potato tubers.

PMID- 14947857
TI  - Dr. Maria Montessori.

PMID- 14947858
TI  - Phase determination in the x-ray diffraction patterns of complex crystals and its
      application to protein structure.

PMID- 14947859
TI  - Binocular eye movements when convergence is subjectively changed.

PMID- 14947860
TI  - Recovery of human red cells after prolonged storage at -79 degrees C.

PMID- 14947861
TI  - Toxicity of aureomycin to guinea pigs.

PMID- 14947862
TI  - A comparison of the electrophoretic patterns of cow, goat and rabbit casein.

PMID- 14947863
TI  - A regulatory mechanism in the posterior ciliary arteries of the dog.

PMID- 14947864
TI  - Hydrolysis and metabolism by soil bacteria of benzoyl-d-phenylalanine.

PMID- 14947865
TI  - Fungi inhibiting growth of the crown-rot disease fungus Sclerotium delphinii
      Welch.

PMID- 14947866
TI  - Genetic recombination in Bact. coli K12; analysis of the stimulating effect of
      ultra-violet light.

PMID- 14947867
TI  - Phoretic association between Simuliidae and crabs.

PMID- 14947868
TI  - Application of the principles of phylembryogenesis to the Protista.

PMID- 14947869
TI  - Spiral roots in agar cultures of Marsilea.

PMID- 14947870
TI  - Role of the sulphydryl group in the formation of alkaline protein gels.

PMID- 14947871
TI  - The changing flora of Britain.

PMID- 14947872
TI  - Mr. R. E. Enthoven, C.I.E.

PMID- 14947873
TI  - DOCTOR A. Lasnitzki.

PMID- 14947874
TI  - Properties of the cytochrome system of living wheat roots.

PMID- 14947875
TI  - An antituberculous substance in tuberculous lymph nodes.

PMID- 14947876
TI  - Action of some water-soluble poly-a-amino-acids on bacteria.

PMID- 14947877
TI  - A relationship between nicotinamide methylkinase and folic acid.

PMID- 14947878
TI  - A reaction of d-glucosamine in the presence of dry protein.

PMID- 14947879
TI  - Populations of Agrostis tenuis resistant to lead and zinc poisoning.

PMID- 14947880
TI  - Relation of nitrogen supply to the molybdenum requirement of cauliflower grown in
      sand culture.

PMID- 14947881
TI  - A tea root disease new to South India.

PMID- 14947882
TI  - The brown alga Durvillea antarctica in Australian waters.

PMID- 14947883
TI  - Autolysis of flight muscles in a mosquito.

PMID- 14947884
TI  - Sugar chromatography of mammary gland extracts.

PMID- 14947885
TI  - Isolation of nitrifying organisms and oxygen supply.

PMID- 14947886
TI  - Biochemical role of vitamin C.

PMID- 14947887
TI  - [The cutaneous form of periarteritis nodosa].

PMID- 14947888
TI  - [Byssinosis].

PMID- 14947889
TI  - [Prognosis of infectious hepatitis].

PMID- 14947890
TI  - [Noradrenalin determination in mixtures of noradrenalin and adrenalin].

PMID- 14947891
TI  - [Agenesia, a congenital defect of the respiratory tract].

PMID- 14947892
TI  - [Jan van Riebeeck as surgeon].

PMID- 14947893
TI  - [A century of ophthalmoscopy].

PMID- 14947894
TI  - [Two penalties imposed because of illegal practice of medicine].

PMID- 14947895
TI  - [Prevention of postvaccinal encephalitis].

PMID- 14947896
TI  - [Problems of short psychotherapy].

PMID- 14947897
TI  - [The task of the obstetrician in congenital defects].

PMID- 14947898
TI  - [Schizoid psychosis after respiratory arrest in eunarcon anesthesia; cerebral
      damages caused by anoxemia].

PMID- 14947899
TI  - [Nitrogen metabolism and blood morphology of three female schizophrenics examined
      during a period of 7 months].

PMID- 14947900
TI  - [Pneumoencephalogram and traumatic cerebral damage after light closed brain
      injuries].

PMID- 14947901
TI  - [Catamnestic examination of patients with brain injuries].

PMID- 14947902
TI  - [Enuresis].

PMID- 14947903
TI  - [Cerebral anatomy and physiology; changes of psychic function after prefrontal
      lobotomy].

PMID- 14947904
TI  - [Recent development of research on aphasia in the U.S..].

PMID- 14947905
TI  - [Role of sympathetic trunc in sensory physiology].

PMID- 14947906
TI  - [Posticteric encephalopathy of newborn].

PMID- 14947907
TI  - [Normal encephalogram in children].

PMID- 14947908
TI  - [Disturbances of creative function in deficiency of senses; comments on the
      agnosia problem].

PMID- 14947909
TI  - [Regulation of mineral metabolism in stress].

PMID- 14947910
TI  - [Intralumbal procedures and stress].

PMID- 14947911
TI  - [The psychic syndrome of diminuted active blood volume].

PMID- 14947912
TI  - [Ophthalmic migraine in arteriovenous aneurysm; symptoms of hemicranias].

PMID- 14947913
TI  - [Prognostic and diagnostic conclusions from the type of response in electroshock
      therapy].

PMID- 14947914
TI  - [Flow of cerebrospinal fluid from caudal to cranial].

PMID- 14947915
TI  - [Loss of memory in electroshock therapy and its reversibility].

PMID- 14947916
TI  - [The problem of compulsory admission of a patient into a mental hospital].

PMID- 14947917
TI  - [Jaspers and psychoanalysis].

PMID- 14947918
TI  - [Pavlovian conference in Krynica].

PMID- 14947919
TI  - [Electrophysiological methods in Pavlovian theory of higher nervous functions].

PMID- 14947920
TI  - [Application of electroencephalography to explanation of dynamics of the cortical
      function].

PMID- 14947921
TI  - [Relationship of structure and function of the cerebral cortex].

PMID- 14947922
TI  - [Actualization of certain premises of Pavlovian theory in a neurological clinic].

PMID- 14947923
TI  - [Pathophysiology of higher nervous functions as a basis of psychiatry].

PMID- 14947924
TI  - [Some psychopathological problems in physiological interpretation].

PMID- 14947925
TI  - [Effect of partial removal of frontal and parietal lobes on conditioned motor
      reflexes].

PMID- 14947926
TI  - [Diagnostic and prognostic deductions resulting from comparison of leukergy with
      the Donaggio reaction].

PMID- 14947927
TI  - [Cerebral bioelectric currents in work and mental fatigue].

PMID- 14947928
TI  - [Spastic paraplegia following ingestion of the seeds of Lathyrus sativus].

PMID- 14947929
TI  - Insulin shock therapy.

PMID- 14947930
TI  - Traumatic war neuroses; a survey of behavior disturbances under combat stress and
      their prophylaxis and treatment.

PMID- 14947931
TI  - Laboratory and clinical studies on erythromycin.

PMID- 14947932
TI  - The early treatment of pulmonary tuberculosis.

PMID- 14947933
TI  - The syndrome of impending hepatic coma in patients with cirrhosis of the liver
      given certain nitrogenous substances.

PMID- 14947934
TI  - Utilization of cholangiogram during exploration for biliary atresia.

PMID- 14947935
TI  - The importance of Coxsackie viruses in human disease, particularly herpangina and
      epidemic pleurodynia.

PMID- 14947936
TI  - Waterhouse-Friderichsen syndrome; report of a case with recovery.

PMID- 14947937
TI  - WEEKLY clinicopathological exercise: struma lymphomatosa (Hashimoto's struma) in
      an eight-and-a-half-year-old girl.

PMID- 14947938
TI  - WEEKLY clinicopathological exercise: glioblastoma multiforme of corpus collosum
      and both frontal lobes, necrotic.

PMID- 14947939
TI  - ERYTHROMYCIN, new and promising antibiotic.

PMID- 14947940
TI  - Arterial hypertension, the therapeutic effect of cation-exchange resins.

PMID- 14947941
TI  - Bulbar poliomyelitis.

PMID- 14947942
TI  - Prognostic significance of the epinephrine test in preoperative patients.

PMID- 14947943
TI  - Hypertrophic pulmonary osteoarthropathy simulating rheumatoid arthritis;
      subsidence after pneumonectomy for carcinoma.

PMID- 14947944
TI  - The importance of Coxsackie viruses in human disease, particularly herpangina and
      epidemic pleurodynia.

PMID- 14947945
TI  - The cardiac Work Classification Unit.

PMID- 14947946
TI  - WEEKLY clinicopathological exercise: polyarteritis nodosa involving kidneys,
      intestine, testicle and periadrenal fat.

PMID- 14947947
TI  - WEEKLY clinicopathological exercise: adenoma, right-lower-lobe bronchus.

PMID- 14947948
TI  - Management of bronchial asthma due to external inhaled factors.

PMID- 14947949
TI  - Bronchial asthma due to intrinsic factors.

PMID- 14947951
TI  - The pharmacology of drugs useful in bronchial asthma.

PMID- 14947950
TI  - Symptomatic treatment of asthma.

PMID- 14947952
TI  - The pharmacology of drugs useful in bronchial asthma; discussion.

PMID- 14947954
TI  - ACUTE and chronic hepatitis.

PMID- 14947953
TI  - OFFICIAL health department policy on immunization of children in summer.

PMID- 14947956
TI  - [Anal abscesses and fistulas; therapeutic results].

PMID- 14947955
TI  - [Anal abscess and fistula; historical review on the disease, its treatment and
      the role of the latter in the progress of surgery].

PMID- 14947957
TI  - [Apicolysis with liquid paraffin filling (oleoplasty)].

PMID- 14947958
TI  - [Acromioclavicular arthroplasty].

PMID- 14947959
TI  - [Talc from surgical glove in surgical wounds and abdominal cavity].

PMID- 14947960
TI  - [The effect of effort in ventricular septum defect with and without overriding
      aorta].

PMID- 14947961
TI  - [Anomalies of the cervical distribution of the internal carotid artery].

PMID- 14947962
TI  - [Attempted evaluation of the relative potency of ethinyl estradiol (linoral) and
      diethylstilbestrol in oral administration].

PMID- 14947963
TI  - [Embryocytological studies on the epithelium of the gastrointestinal canal and
      its role in erythropoiesis].

PMID- 14947964
TI  - [Social factors in uterine cancer].

PMID- 14947965
TI  - [Decamethonium iodide as a muscle relaxant in anesthesia].

PMID- 14947967
TI  - [Excision and skin transplantation in varicose ulcus cruris].

PMID- 14947966
TI  - [Diet therapy in celiac disease].

PMID- 14947968
TI  - [Studies on bone marrow in multiple sclerosis].

PMID- 14947969
TI  - [Barberry and privet as a remedy for scurvy].

PMID- 14947970
TI  - [Traumatic diabetes mellitus].

PMID- 14947971
TI  - [Slow-acting ACTH; preliminary investigation of the effect of cortico-depot].

PMID- 14947972
TI  - [Kymographic recording of colonic motility in normal and pathological
      conditions].

PMID- 14947973
TI  - [The effect of vegolysen in hypertension].

PMID- 14947974
TI  - [Diabetes mellitus and chronic polyarthritis].

PMID- 14947975
TI  - [Cases of bronchostenosis of different etiology].

PMID- 14947976
TI  - [Diabetes and insurance].

PMID- 14947977
TI  - In memoriam Carl Edvard Bloch.

PMID- 14947978
TI  - [Nutrition and clinical treatment].

PMID- 14947979
TI  - [X-ray and physical examination of the lumbar spinal function in the lumbago
      sciatic syndrome].

PMID- 14947980
TI  - [Evaluation of x-ray functional examination in lumbar disc prolapse].

PMID- 14947981
TI  - [Paper chromatography of sugar in the urine in pregnancy].

PMID- 14947982
TI  - [Intrauterine transmission of paratyphus].

PMID- 14947983
TI  - [Surgical injuries in biliary operations].

PMID- 14947984
TI  - [The role of infection intensity in tuberculosis].

PMID- 14947985
TI  - [Renal venous catheterization].

PMID- 14947986
TI  - [Diagnosis and clinical results in treatment of bulbospinal poliomyelitis].

PMID- 14947987
TI  - [Microspectrographic examination of tumors].

PMID- 14947988
TI  - [Endocrine genital disorders in boys].

PMID- 14947989
TI  - [Functional diagnosis in physical medicine].

PMID- 14947990
TI  - [Not Available].

PMID- 14947991
TI  - [Sulfurated preparations and iodine in surgery of thyrotoxicoses].

PMID- 14947992
TI  - [Resins in cardiac insufficiency].

PMID- 14947993
TI  - [Recurrent meningitis].

PMID- 14947994
TI  - [Lactose and galactose determination in blood and urine in pregnant women].

PMID- 14947995
TI  - [Pethidine anesthesia in peroral endoscopy].

PMID- 14947996
TI  - [Acute toxoplasmosis with lymphadenopathy and chorioretinitis in adults].

PMID- 14947997
TI  - [Acute toxoplasmosis in infant].

PMID- 14947998
TI  - [Acute toxoplasmosis in infant].

PMID- 14947999
TI  - [Multiple lung infiltrations in shock with high sedimentation rate].

PMID- 14948000
TI  - [Antagonism of antibiotics].

PMID- 14948001
TI  - [Prognosis in psychotherapy].

PMID- 14948002
TI  - [Monteggia's fracture].

PMID- 14948003
TI  - [McLaughlin's osteosynthesis in pertrochanteric femur fractures].

PMID- 14948004
TI  - [A dilemma of human genetics].

PMID- 14948005
TI  - [Paper electrophoresis].

PMID- 14948006
TI  - [Subacute thyroiditis; a case with x-ray therapy].

PMID- 14948007
TI  - [Cassette holder for nailing of femoral neck fractures].

PMID- 14948008
TI  - [Cassette box for cholangiography].

PMID- 14948009
TI  - [Autoradiographic studies on the rabbit ovary after P32 injection].

PMID- 14948010
TI  - [Cryptorchism; follow-up of case after Torek operation].

PMID- 14948011
TI  - [Results in ca. 200 plombage operations in pulmonary tuberculosis over a period
      of 2 1/2 years].

PMID- 14948012
TI  - [The gastric resection syndrome].

PMID- 14948013
TI  - [Gastric obstruction after Billroth II].

PMID- 14948014
TI  - [Pleuropulmonary complications after laparotomy in the upper abdomen].

PMID- 14948015
TI  - [Results with intravenous feeding of amino acids].

PMID- 14948016
TI  - [Surgical therapy of Bennett's fracture].

PMID- 14948018
TI  - [Hyaluronidase formation by streptococci].

PMID- 14948017
TI  - [Rickets in Kiruna].

PMID- 14948019
TI  - [The incidence of ear diseases and prevention of deafness].

PMID- 14948020
TI  - [Micro-sedimentation rate in school children 6-16 years of age].

PMID- 14948021
TI  - [Cortone therapy in children].

PMID- 14948022
TI  - [Anal fistulas and their treatment].

PMID- 14948023
TI  - [Chloromycetin therapy of pertussis encephalitis].

PMID- 14948024
TI  - [Follow-up of female patients with lighter mental disorders; preliminary report].

PMID- 14948025
TI  - [Medical journals in Norway; a comparison with the library of Karolinska
      Institute and Quarterly Cumulative Index Medicus].

PMID- 14948026
TI  - [Acute heart infarct after allergic reaction to immune serum].

PMID- 14948027
TI  - [Occlusion of the ulnar artery after repeated trauma].

PMID- 14948029
TI  - [Bronchoscopy of tuberculous patients].

PMID- 14948028
TI  - [Problems of compiling tuberculosis statistics].

PMID- 14948030
TI  - [The reliability of x-ray interpretation and the value of control
      interpretation].

PMID- 14948031
TI  - [Diagnostic value of liver puncture].

PMID- 14948032
TI  - [Treatment of perforated ulcer].

PMID- 14948033
TI  - [Industrial health service in Great Britain].

PMID- 14948034
TI  - [Modern treatment of syphilis].

PMID- 14948035
TI  - [Development of resistance in bacteria].

PMID- 14948036
TI  - [Practical method of resistance determination for tubercle bacilli. I].

PMID- 14948037
TI  - [Practical method of resistance determination for tubercle bacilli. II].

PMID- 14948038
TI  - [Theories and statistics of cancer].

PMID- 14948039
TI  - [Idiopathic hypochromic anemia in young men].

PMID- 14948040
TI  - [Hereditary idiopathic hypotonic joints].

PMID- 14948041
TI  - [Rise in temperature as a symptom of cardiac incompensation].

PMID- 14948042
TI  - [Cardiac infarct during thyroxin therapy of myxedema].

PMID- 14948043
TI  - [Symmetrical parietal fenestrae in members of one family].

PMID- 14948044
TI  - [Electron rays].

PMID- 14948045
TI  - [Plan for preventive mass surveys in Sweden].

PMID- 14948046
TI  - [Names approved by the Scandinavian pharmacopeia committee; list No. 9].

PMID- 14948047
TI  - [Corneal sensitivity with special consideration of clinical examination methods].

PMID- 14948048
TI  - [The anatomical substratum of consciousness in the light of recent
      neurophysiological studies].

PMID- 14948049
TI  - [Problem children and EEG; EEG of pupils in a school for asocial children].

PMID- 14948050
TI  - [Phenylacetyl carbamide in epilepsy therapy].

PMID- 14948051
TI  - [Complications of mumps during an epidemic].

PMID- 14948052
TI  - [Differential diagnosis of malignant tumors of the testes].

PMID- 14948053
TI  - [The fertility of males born in breech presentation].

PMID- 14948054
TI  - [Cerebral effect in children after overdosage with antihistamins].

PMID- 14948055
TI  - [Coarctation of the aorta with subarachnoid hemorrhage].

PMID- 14948056
TI  - [Diuretics].

PMID- 14948057
TI  - [Literary review of the geography of disease].

PMID- 14948058
TI  - [Separation of substance injected in blood].

PMID- 14948059
TI  - [Skin infection caused by a new type of Mycobacterium in swimming pools].

PMID- 14948060
TI  - [Legally induced abortions at the Helsinki gynecological clinic].

PMID- 14948061
TI  - [Uterine rupture in cesarean section cicatrix; general considerations and
      prevention].

PMID- 14948062
TI  - [Fenestration in Bartholin cysts].

PMID- 14948063
TI  - [Meniscus calcification in hyperparathyroidism].

PMID- 14948064
TI  - [Tuberculosis of the tongue].

PMID- 14948065
TI  - [Treatment of pseudarthrosis of the femoral neck and luxation fracture of the
      femoral head].

PMID- 14948066
TI  - [Treatment and prognosis of knee dislocation].

PMID- 14948067
TI  - [Sprain and ligament injury of the ankle].

PMID- 14948068
TI  - [Treatment of lateral ruptures of the ankle ligaments].

PMID- 14948069
TI  - [Primary resection in perforated peptic ulcer].

PMID- 14948070
TI  - [Reoperation after simple suture in perforated ulcer].

PMID- 14948071
TI  - [Penicillin therapy of suppurative eczema of the external auditory canal].

PMID- 14948072
TI  - [Current medical and social-medical problems in infant homes].

PMID- 14948073
TI  - [Positive pressure respiration in therapy of pulmonary edema].

PMID- 14948074
TI  - [Complete heart block; analysis of 24 cases].

PMID- 14948075
TI  - [Cancer in pregnancy].

PMID- 14948076
TI  - [Not Available].

PMID- 14948077
TI  - [Peroral beta-naphthyl dichloroethylamine therapy of polycythemia vera].

PMID- 14948078
TI  - [Determination of tissue metabolism].

PMID- 14948079
TI  - [24 hour creatinine clearance].

PMID- 14948080
TI  - [Not Available].

PMID- 14948081
TI  - [Course and prognosis of periarthrosis humeroscapularis].

PMID- 14948082
TI  - [Two cases of the vena cava superior syndrome].

PMID- 14948083
TI  - [Uremia and azotemia].

PMID- 14948084
TI  - [Experimental studies on the effect of estrin on certain tumors in mice,
      especially breast carcinoma].

PMID- 14948085
TI  - [So-called dyspeptic intestinal distress].

PMID- 14948086
TI  - [Bronchial asthma; diagnosis and surgical therapy].

PMID- 14948087
TI  - [Autoradiographic studies on sulfate fixation].

PMID- 14948088
TI  - [Etiology and a new treatment of progressive muscular dystrophy].

PMID- 14948089
TI  - [Pyrogenic properties of exudates].

PMID- 14948090
TI  - [Meduna's carbon dioxide therapy of psychoneuroses].

PMID- 14948091
TI  - [Carbon monoxide determination in blood].

PMID- 14948092
TI  - [Choreal movements of the tongue in paralytic dementia].

PMID- 14948093
TI  - [Dystrophic liver disease in swine suggesting acute yellow atrophy].

PMID- 14948094
TI  - [Malnutrition causing myocardiac damage].

PMID- 14948095
TI  - [The cerebral blood circulation].

PMID- 14948096
TI  - [Streptokinasestreptodornase therapy of coagula and postoperative empyema].

PMID- 14948097
TI  - [Anovular cycles].

PMID- 14948098
TI  - [Conservative and active delivery, with special reference to prolonged labor].

PMID- 14948099
TI  - [The advisability of routine blood transfusions in operations].

PMID- 14948100
TI  - [Meningo-polyradiculitis after a tick bite].

PMID- 14948101
TI  - [Hearing disorders caused by dihydrostreptomycin administration].

PMID- 14948102
TI  - [Intravenous avertin].

PMID- 14948103
TI  - [Reiter's syndrome, prostatovesiculitis and infectious abacterial pyuria].

PMID- 14948104
TI  - [Lipoprotein studies].

PMID- 14948105
TI  - [The pathogenesis of the dumping syndrome].

PMID- 14948106
TI  - [Hearing disorders after dihydrostreptomycin therapy].

PMID- 14948107
TI  - [Polycythemia vera, radioactive phosphorus, acute leukemia].

PMID- 14948108
TI  - [Cutaneous allergy].

PMID- 14948109
TI  - Diabetes and pregnancy; blood sugar of newborn infants during fasting and glucose
      administration.

PMID- 14948110
TI  - [Gluconeogenesis from oleic acid in the perfused cat liver].

PMID- 14948111
TI  - Early experiences with vitamin A--a retrospect.

PMID- 14948112
TI  - URIC acid and creatine metabolism in man.

PMID- 14948113
TI  - THYROID uptake of iodine in goiter.

PMID- 14948114
TI  - THE dietary treatment of atherosclerosis in man.

PMID- 14948115
TI  - CORTISONE and act in nontropical sprue.

PMID- 14948116
TI  - INFLUENCE of nonprotein calories on protein metabolism.

PMID- 14948117
TI  - METABOLISM of dietary cholesterol by the liver.

PMID- 14948118
TI  - VITAMIN B12, antibiotics and egg hatchability.

PMID- 14948119
TI  - COBALT deficiency in lambs.

PMID- 14948120
TI  - GROWTH factors for poultry.

PMID- 14948121
TI  - DIETARY factors in dairy cattle nutrition.

PMID- 14948122
TI  - BODY composition.

PMID- 14948123
TI  - NEW pantothenic acid antagonist for animal experimentation.

PMID- 14948124
TI  - AMINO acids and lipotropism.

PMID- 14948125
TI  - VITAMIN needs during reproduction.

PMID- 14948126
TI  - CARBONATE in the synthesis of milk constituents.

PMID- 14948127
TI  - EXPERIMENTAL potassium depletion in man.

PMID- 14948128
TI  - Radiological estimation of pelvic capacity.

PMID- 14948129
TI  - [Failure of penicillin and excellent effect of poly-microbic vaccination on
      accidental skin infections in total rhinoplasty].

PMID- 14948130
TI  - [12th Congress of French Stomatology, Paris, 8-13 October 1951].

PMID- 14948131
TI  - [Bucco-dental prophylaxis].

PMID- 14948132
TI  - [Evolution of dental hygiene].

PMID- 14948133
TI  - [Studies on tissue therapy in pyorrhea alveolaris].

PMID- 14948134
TI  - [History of otorhinolaryngology].

PMID- 14948135
TI  - [Ionophoresis, complementary technic].

PMID- 14948136
TI  - [Self-polymerizing resins in operative dentistry].

PMID- 14948137
TI  - [Partial syndesmotomy in therapy of paradentosis].

PMID- 14948138
TI  - [Homeopathic therapy of bucco-dental affections and infections in daily
      practice].

PMID- 14948139
TI  - [The requirements of municipal hygiene with special reference to the
      reconstruction of destroyed cities].

PMID- 14948140
TI  - [Rural sanitation].

PMID- 14948141
TI  - [Public health doctor and the water supply].

PMID- 14948142
TI  - [Agricultural utilization of waste water].

PMID- 14948143
TI  - [Housing conditions and the public health officials].

PMID- 14948144
TI  - [Food sanitation as the legal responsibility of the public health doctor].

PMID- 14948145
TI  - [Diphtheria, scarlet fever and whooping-cough vaccination Kreis Schluchtern].

PMID- 14948146
TI  - [Sociohygienic criteria for the compulsory treatment of venereal disease].

PMID- 14948147
TI  - [Proposal for improvement of statistics on breast feeding].

PMID- 14948149
TI  - [Place and valuation of Boeck's disease in expert opinion].

PMID- 14948148
TI  - [Infectivity of scarlet fever after penicillin therapy].

PMID- 14948151
TI  - [Fifty-year old order concerning drug trade since October 22, 1901].

PMID- 14948150
TI  - [Boeck-Besnier-Schaumann's disease in tuberculosis care].

PMID- 14948152
TI  - [Supplement to the evaluation of blood-alcohol findings].

PMID- 14948153
TI  - [Course on drinking water supply].

PMID- 14948154
TI  - [Subcutaneous smallpox vaccination].

PMID- 14948155
TI  - [Parenteral therapy and prophylaxis with human milk].

PMID- 14948156
TI  - [Sturge-Weber's syndrome].

PMID- 14948157
TI  - [Pathogenesis of chest deformities in rickets].

PMID- 14948158
TI  - [Congenital syphilis].

PMID- 14948159
TI  - [Etiological importance of Bacterium coli 111 B 4 in infantile diarrhea].

PMID- 14948160
TI  - [Effects of different antibiotics on the intestinal flora in infantile diarrhea].

PMID- 14948161
TI  - [Experiences with hydantal Sandoz and Mesantoin in the therapy of epilepsy of
      children].

PMID- 14948162
TI  - [Analysis of the complications after BCG inoculations reported to the Austrian
      Health authorities].

PMID- 14948163
TI  - [Infantile mortality & morbidity in Austria; control].

PMID- 14948164
TI  - [Vienna Pediatrics Society].

PMID- 14948165
TI  - [To professor Dr. E. Glanzmann on his 65th birthday].

PMID- 14948166
TI  - [A case of fibrous dysplasia of the skeletal system (Lichtenstein-Jaffe) in a 5
      1/2 year old boy].

PMID- 14948167
TI  - [Pantothenic acid therapy of hyperthyroidism in a newborn].

PMID- 14948168
TI  - [The pathogenesis of changes of the teeth in infants following icterus gravis].

PMID- 14948169
TI  - [Postvaccinal encephalitis of a 7 month old baby].

PMID- 14948170
TI  - [Acute hemolytic anemia (type Lederer-Brill) and constitutional icterus].

PMID- 14948171
TI  - [Hepatoma in a newborn].

PMID- 14948172
TI  - [Pseudofracture (chronic fracture) in infancy].

PMID- 14948173
TI  - [Pancreatic insufficiency in chronic amino acid uria].

PMID- 14948174
TI  - [Human milk therapy in chorea minor].

PMID- 14948175
TI  - [Urticaria pigmentosa bullosa partim nodosa].

PMID- 14948176
TI  - [Variations of poliomyelitis].

PMID- 14948177
TI  - [Clinical diagnosis and pathology of malignant neoplasms of the sympathetic
      nervous system].

PMID- 14948178
TI  - [Transposition of all pulmonary veins into the right atrium; critique on the
      functional closure mechanism of the ductus arteriosus Botalli].

PMID- 14948180
TI  - [Pathogenesis and symptoms of Mauriac's syndrome].

PMID- 14948181
TI  - [Precession of infestation and silent immunisation in poliomyeliti].

PMID- 14948182
TI  - [Therapeutic effects of sulfonamides and penicillin in acute otitis of newborn
      and infants].

PMID- 14948183
TI  - [Mongoloid idiocy in siblings; three cases].

PMID- 14948184
TI  - [Protective effect of fluoridation in school children who came postnatally into
      fluoridation areas].

PMID- 14948185
TI  - [Catamnestic investigations on therapeutic results of epidemic meningitis].

PMID- 14948186
TI  - [Social-hygienic studies on the increase of dental caries in the 19th century and
      the decrease of dental caries in the 20th century].

PMID- 14948187
TI  - [The muscular action of the Andresen-Haupl apparatus].

PMID- 14948188
TI  - [Progress in full dental prosthesis].

PMID- 14948190
TI  - [Serial examinations on the genesis of dentition abnormalities].

PMID- 14948189
TI  - [Practical dentistry in England].

PMID- 14948191
TI  - [Dentofacial orthopedics and practical orthodontics].

PMID- 14948192
TI  - [The so-called prosthesis fibroma].

PMID- 14948193
TI  - [Methods of osteoplastic of the jaw].

PMID- 14948194
TI  - [Stomatological prophylaxis and therapy in avoiding professional injuries].

PMID- 14948196
TI  - [30 years of school dental service in Vienna].

PMID- 14948195
TI  - [Privin, a new vasoconstrictive supplement to local anesthetics].

PMID- 14948197
TI  - [Suggestion to classify gingiva diseases with reference to the number of
      Treponema vincenti present].

PMID- 14948198
TI  - [The periodic granuloma filling with apicoflux de Trey].

PMID- 14948199
TI  - [Paradentosis of the cave-bear and some hominid fossils].

PMID- 14948200
TI  - [Caries prevention with fluorine].

PMID- 14948201
TI  - [The interdental margin].

PMID- 14948202
TI  - [Retrograde root canal filling].

PMID- 14948203
TI  - [Septic jaw surgery before and after introduction of penicillin].

PMID- 14948204
TI  - [Movable connection for free-end prosthesis, especially apt for social practice].

PMID- 14948205
TI  - [Use of anitinum preparations in dentistry].

PMID- 14948206
TI  - Important implications of the plus three error of refraction.

PMID- 14948207
TI  - The sweating test in sympathectomy.

PMID- 14948208
TI  - Depressive reactions as a cause of chronic invalidism.

PMID- 14948209
TI  - The treatment of congestive heart failure with cation exchange resins--a review
      of the literature and report of results in thirty cases.

PMID- 14948210
TI  - Bentyl hydrochloride in the treatment of psychosomatic disorders.

PMID- 14948211
TI  - Rupture of the spleen due to sarcoidosis.

PMID- 14948212
TI  - Thrombo-angiitis obliterans treated with cortisone; report of a case.

PMID- 14948213
TI  - Medical agents and equipment used in the northwest territory.

PMID- 14948214
TI  - NEW president-elect of the Association.

PMID- 14948215
TI  - [The masticatory musculature of Bufo vulgaris japonica during metamorphosis].

PMID- 14948216
TI  - Phase contrast microscopy of liver cells of a fish (Oryzias latipes). I.
      Intracellular structures of liver cells in fresh crush preparations and their
      change with the time.

PMID- 14948217
TI  - Phase contrast microscopy of liver cells of a fish (oryzias latipes). II. Changes
      of intracellular structures of the fresh crush preparations during the
      application of fixing solutions.

PMID- 14948218
TI  - On the leucofuchsin staining after oxidation.

PMID- 14948219
TI  - On the mitochondria, ribonucleic acid, acid phosphatase and polysaccharide of
      liver cells of a fish (Oryzias latipes) during starvation. I. On the mitochondria
      and ribonucleic acid.

PMID- 14948220
TI  - On the golgi apparatus, alkaline phosphatase and protein of liver cells of a fish
      (Oryzias latipes) during starvation. I. On the golgi apparatus.

PMID- 14948221
TI  - Cytochemical studies on polysaccharide and protein of ovarian egg-cells of an
      osseous fish (Leiognathus argenteum).

PMID- 14948222
TI  - [Distribution of mm. arrectores pilorum in the skin of the nose].

PMID- 14948223
TI  - [Benign ocular lymphoreticulosis].

PMID- 14948224
TI  - [The relation of apparent tightening to permeability increase in the lens in non
      electrolyte solutions].

PMID- 14948225
TI  - [Two cases of ocular hypertension after oophorohysterectomy].

PMID- 14948226
TI  - [My simplified modification of external dacryocystorhinostomy without sutures].

PMID- 14948227
TI  - Stargardt's degeneration of the retina with neurological and endocrine
      complications.

PMID- 14948228
TI  - [Motion vision and the whiplash illusion].

PMID- 14948229
TI  - Alternating hyperphoria.

PMID- 14948230
TI  - A hole in the macula in syphilitic subjects.

PMID- 14948231
TI  - Secondary tapetoretinal degeneration.

PMID- 14948232
TI  - A new syndrome, of importance for oculists and ear specialists.

PMID- 14948233
TI  - Lens changes in alloxan diabetes.

PMID- 14948234
TI  - Bilateral cortics hemianopsia and optokinetic nystagmus.

PMID- 14948235
TI  - Tumors of the jaws.

PMID- 14948236
TI  - Clinical report of a case of globulomaxillary cyst.

PMID- 14948237
TI  - Osteomyelitis of the mandible following the extraction of teeth.

PMID- 14948238
TI  - A description of the antibiotic bacitracin: its topical use in the treatment of
      Vincent's infection.

PMID- 14948239
TI  - Preanesthetic evaluation of the oral surgical patient.

PMID- 14948240
TI  - Gingivitis gravidarum; studies on clinic and on etiology with special reference
      to the influence of vitamin C.

PMID- 14948241
TI  - Intracutaneous tests using filtrates prepared from pathologic pulps of human
      teeth, with special reference to rheumatoid arthritis.

PMID- 14948242
TI  - The oral characteristics of guamanians including the effects of betel chewing on
      the oral tissues.

PMID- 14948243
TI  - Synergistic effect of saliva with aureomycin and terramycin.

PMID- 14948244
TI  - Ameloblastoma of the mandible.

PMID- 14948245
TI  - [Pathogenesis of tubercular meningitis; anatomical, pathological and statistical
      study].

PMID- 14948246
TI  - [A decade of surgical activity in the Division; operations for calculi of the
      principal biliary tract].

PMID- 14948247
TI  - [A case of delayed, recurrent tetanus].

PMID- 14948248
TI  - [Hydatid cyst of the thyroid gland].

PMID- 14948249
TI  - [Acute benign pericarditis].

PMID- 14948250
TI  - [Two cases of traumatic subcutaneous rupture of the duodenum].

PMID- 14948251
TI  - [Social service and charity at the Polyclinic Hospital of Milan].

PMID- 14948252
TI  - [Observations on 126 cases of tetanus].

PMID- 14948253
TI  - [Post-operative determination of capillary permeability with Landis test].

PMID- 14948254
TI  - [Clinical aspects and physiopathology of artificial pneumoperitoneum in pulmonary
      tuberculosis].

PMID- 14948255
TI  - [New contributions to the study of spontaneous hematomas of the abdominal wall;
      clinical, etiopathogenic, and histopathologic observations on a case of rupture
      of the epigastric artery].

PMID- 14948256
TI  - [Case of hypoglobulinemic disproteinemia with anasarca in infant].

PMID- 14948257
TI  - [Clinicopsychological and Rorschach profiles of slight sexual obsessions in daily
      practice].

PMID- 14948258
TI  - [Abscess of the frontal lobe].

PMID- 14948259
TI  - [Humoral picture in progressive paralysis with penicillin therapy].

PMID- 14948260
TI  - [Desensitizing properties of bile and bile acids].

PMID- 14948261
TI  - [Desensitizing properties of dehydrocholic acid].

PMID- 14948262
TI  - [Leukocyte index in typhoid and paratyphoid B].

PMID- 14948263
TI  - [New classification of craniostenosis].

PMID- 14948264
TI  - [Sebaceous navue and its relation to epitheliomata].

PMID- 14948265
TI  - [Systemic pigmentation changes].

PMID- 14948266
TI  - [Data and considerations on certain tumors observed in children in the last 15
      years in the Pediatric Clinic in Naples].

PMID- 14948267
TI  - [Retropneumoperitoneum in diagnosis of abdominal conditions in children].

PMID- 14948268
TI  - [Filatov's placental tissue therapy of diseases of nutrition].

PMID- 14948269
TI  - [Mediterraneal exanthematous fever; clinical and statistical study with special
      reference to Genoa].

PMID- 14948270
TI  - [Vollmer's tuberculin reaction with addition of vitamins].

PMID- 14948271
TI  - [Considerations on use of chloramphenicol in the treatment of measles].

PMID- 14948273
TI  - [Case of bilateral Bonnevie-Ullrich syndrome].

PMID- 14948272
TI  - [Fibroflavin deficiency in infant].

PMID- 14948274
TI  - [Position of Jaksch-Hayem-Luzet anemia in the field of blood diseases in
      children].

PMID- 14948275
TI  - [Use of hyaluronidase in therapy and diagnosis with special reference to
      children].

PMID- 14948276
TI  - [BCG vaccination of the newborn with a single concentrated and increased dose].

PMID- 14948277
TI  - [Pulmonary emphysema in tuberculous cerebrospinal meningitis].

PMID- 14948278
TI  - [Causes of failure of treatment in tuberculous meningitis in children].

PMID- 14948279
TI  - [Effect of intravenously administered insulin on the cerebrospinal fluid sugar
      level in children treated by streptomycin].

PMID- 14948280
TI  - [Intraperitoneal blood transfusion in infants and small children].

PMID- 14948281
TI  - [Foreign bodies in the alimentary canal (with the exception of esophagus) in
      children].

PMID- 14948282
TI  - [Lactarium, its organization and technique of milk collection].

PMID- 14948283
TI  - [The symptom of frog-like position in the course of chronic tuberculous
      meningitis treated with streptomycin].

PMID- 14948284
TI  - [Acute pseudobulbar syndrome in the course of rheumatism in a five years old
      boy].

PMID- 14948285
TI  - [A case of leukemia in a child treated with aminopterin, and a case of leukemic
      reaction in the course of infection].

PMID- 14948286
TI  - [Two cases of malignant lymphogranulomatosis in children].

PMID- 14948287
TI  - [Physical education in tuberculosis sanatoria and preventoria for children].

PMID- 14948288
TI  - [A child predisposed to colds].

PMID- 14948289
TI  - [Studies on vitamin C level in blood serum in infants and children].

PMID- 14948290
TI  - [Atypic pneumonias].

PMID- 14948291
TI  - [Pediatric aspects of otitis media in the course of diarrhea].

PMID- 14948292
TI  - [Case of paranasal sinusitis complicated by maxillary osteomyelitis in a child].

PMID- 14948293
TI  - [Experimental studies on bacteriostatic effect of ultraviolet rays in pediatric
      wards].

PMID- 14948294
TI  - [Case of Tay-Sachs disease].

PMID- 14948295
TI  - [Case of Bang's disease in a 12 year old girl].

PMID- 14948296
TI  - [Comparative evaluation of human and cow's milk in infant nutrition].

PMID- 14948297
TI  - [Observations on complications following oral administration of BCG vaccine].

PMID- 14948298
TI  - [Acute peritonitis in infants and young children].

PMID- 14948299
TI  - [Blood phosphorus and phosphatases in children in Heine-Medin disease].

PMID- 14948300
TI  - [Effect of hyaluronidase on McClure-Aldrich skin water test in pediatric
      diseases].

PMID- 14948301
TI  - [Clinical course of acute diarrhea according to epicrisis of 30 infants submitted
      to laboratory investigation].

PMID- 14948302
TI  - [Blood transfusion into the bone marrow in infants].

PMID- 14948303
TI  - [Mediastinal, pleural, and subcutaneous pneumothorax in newborn].

PMID- 14948304
TI  - [Case of extradural abscess].

PMID- 14948305
TI  - [Case of pancytopenia splenica].

PMID- 14948306
TI  - [Pavlovian conference in Krynica].

PMID- 14948307
TI  - [Breast feeding by working mothers].

PMID- 14948309
TI  - [Spontaneous pneumothorax in infants].

PMID- 14948308
TI  - [Treatment of rheumatic diseases in children in general practice].

PMID- 14948310
TI  - [Trypsin and diastase in acute nutritional disorders in infants].

PMID- 14948311
TI  - [Frequency and causes of premature labor and early mortality of prematures].

PMID- 14948312
TI  - [Results of streptomycin and paraaminosalicylic acid therapy of tuberculosis in
      children].

PMID- 14948313
TI  - [Penicillin therapy and problem of early ambulation in scarlet fever].

PMID- 14948314
TI  - [Hospitalization in scarlet fever in children].

PMID- 14948315
TI  - [Clinical aspect of precocious puberty].

PMID- 14948316
TI  - [Case of generalized staphylococcal infection].

PMID- 14948317
TI  - [Case of lumbar meningocele complicated by hemorrhage].

PMID- 14948318
TI  - [Epidemiology and Heine-Medin disease].

PMID- 14948319
TI  - [Clinical aspects of manifestations of poliomyelitis during the last epidemic and
      their significance in early diagnosis].

PMID- 14948320
TI  - [Clinical course of Heine-Medin disease with special reference to epidemic in
      Lodz and Lodz region in 1951].

PMID- 14948321
TI  - [Characteristics of the course of Heine-Medin disease in acute stage in patients
      treated in Warsaw in 1951].

PMID- 14948322
TI  - [Analysis of cases of erroneously diagnosed Heine-Medin disease].

PMID- 14948323
TI  - [Rehabilitation in Heine-Medin disease].

PMID- 14948324
TI  - [Effect of stimulating substances with special reference to dibazol after
      subsiding of acute symptoms].

PMID- 14948325
TI  - [Unusual form of chloroma of the bone marrow in a 12-year-old girl].

PMID- 14948326
TI  - [Case of fragilitas ossium in infant].

PMID- 14948327
TI  - [Eosinophilic granuloma].

PMID- 14948328
TI  - [Case of cat scratch disease in a 12-year-old girl].

PMID- 14948329
TI  - [Plan for medical specialization according to the decision of the Ministry of
      Health].

PMID- 14948330
TI  - [Neuropsychopathic children].

PMID- 14948331
TI  - [Prothrombinemia in acute gastrointestinal disturbances in early infancy].

PMID- 14948332
TI  - [Distention of the hypogastrium].

PMID- 14948333
TI  - [Project for pediatric health centers in new socialistic centers in Ostrava].

PMID- 14948334
TI  - [New tables on body weight and height in school children (except Prague)].

PMID- 14948335
TI  - [Parasitic pneumonia due to Pneumocystis carinii; interstitial plasma cell
      pneumonia in prematures].

PMID- 14948336
TI  - [Progress of pediatric urography].

PMID- 14948337
TI  - [Clinical aspects of erythroblastosis fetalis].

PMID- 14948338
TI  - [Significance of fetal hemoglobin].

PMID- 14948339
TI  - [Infectious diseases in adolescents].

PMID- 14948340
TI  - [Role of tuberculosis in child mortality and morbidity].

PMID- 14948341
TI  - [Nocturnal enuresis in children; pathogenesis and therapy].

PMID- 14948342
TI  - [Indication for spinal administration of antibiotics in suppurative meningitis].

PMID- 14948343
TI  - [Significance of malrotation in pediatric surgery].

PMID- 14948344
TI  - [Congenital abnormalities of the upper extremities].

PMID- 14948345
TI  - [Poisoning with antihistamine Spofa].

PMID- 14948346
TI  - [Health and social education of youth].

PMID- 14948347
TI  - [Cosmopolitism and objectivism in pediatrics in Czechoslovakia].

PMID- 14948348
TI  - [Cosmopolitism and infectious diseases].

PMID- 14948349
TI  - [Law concerning children infected with reportable diseases].

PMID- 14948350
TI  - The treatment of acute poliomyelitis.

PMID- 14948351
TI  - Peritonitis-diagnosis and modern trends in treatment.

PMID- 14948352
TI  - Evaluation of the cancer detection program.

PMID- 14948353
TI  - Surgery of the esophagus.

PMID- 14948354
TI  - Convalescence and rehabilitation.

PMID- 14948355
TI  - The structure of tee tables in medical service insurance.

PMID- 14948356
TI  - Biblical and talmudic medicine. IV.

PMID- 14948357
TI  - A report on Permanente's first ten years.

PMID- 14948358
TI  - A morbidity study of the Permanente health plan population; II: comparison of
      utilization and morbidity data with experience of other population groups.

PMID- 14948359
TI  - The usefulness of intravenous lanatoside C in paroxysmal ventricular tachycardia
      not due to myocardial infarction.

PMID- 14948360
TI  - A review of the clinical uses of veratrum alkaloids.

PMID- 14948361
TI  - The pressor action of atropine in veratrum alkaloid (veriloid) induced
      hypotension.

PMID- 14948362
TI  - Clinical experiences with veratrum alkaloids (veriloid) in the prolonged
      treatment of essential hypertension.

PMID- 14948363
TI  - Failure of veriloid to control hypertension; study of 30 clinic patients.

PMID- 14948364
TI  - Hypersensitive carotid sinus reflex; two cases treated by surgical denervation.

PMID- 14948365
TI  - Comparison of cholecystography with iodoalphionic acid (priodax) and a new
      gallbladder dye, iodopropanoic acid (telepaque).

PMID- 14948366
TI  - Irradiatio treatment of hearing loss in children.

PMID- 14948367
TI  - The treatment of congenital ptosis by the Blaskovics technique.

PMID- 14948368
TI  - The role of insulin induced hypoglycemia in the treatment of rheumatoid arthritis
      and certain other diseases.

PMID- 14948369
TI  - Insulin hypoglycemia in treatment of rheumatoid arthritis; preliminary
      observations of eleven patients.

PMID- 14948370
TI  - Insulin hypoglycemia in treatment of gout; preliminary observations on three
      cases.

PMID- 14948371
TI  - Serum sickness successfully treated with insulin induced hypoglycemia.

PMID- 14948372
TI  - Insulin hypoglycemia in treatment of psoriasis with temporary improvement; two
      case reports.

PMID- 14948373
TI  - Insulin hypoglycemia in treatment of narcolepsy with temporary improvement.

PMID- 14948374
TI  - Giant urticaria successfully treated with insulin induced hypoglycemia; two case
      reports.

PMID- 14948375
TI  - Effect of quercitrin on hepatic and splenic manifestations of mouse pox.

PMID- 14948376
TI  - A simple diffusion apparatus for biochemical analyses; its application in CO,
      CO2, NH3, and urea determinations.

PMID- 14948377
TI  - Spectrophotometric determination of arginine and arginine-containing proteins in
      sera.

PMID- 14948378
TI  - Some remarks on pain as a diagnostic aid and biologic phenomenon.

PMID- 14948379
TI  - Central facilitation; the basis of treatment for paralysis.

PMID- 14948380
TI  - Electrical stimulation of antagonist muscles in the relaxation of spasticity.

PMID- 14948381
TI  - Dynamics of normal voluntary motion in man.

PMID- 14948382
TI  - Problems in the treatment of viral pneumonia.

PMID- 14948383
TI  - Allergic diseases of the lung.

PMID- 14948384
TI  - A statistical analysis of 200 hospitalized cases of bronchial asthma.

PMID- 14948385
TI  - Physical allergy.

PMID- 14948387
TI  - Primary regional jejunitis successfully treated with ACTH.

PMID- 14948386
TI  - Aberrant intrathoracic goiter.

PMID- 14948388
TI  - An explanation of enteroliths; with report of a case.

PMID- 14948389
TI  - Repair of defects in the sternum.

PMID- 14948390
TI  - Adverse effects of carbon dioxide excess.

PMID- 14948391
TI  - Problems in the management of viral diseases of the skin.

PMID- 14948392
TI  - Endocrines in relationship to acne vulgaris.

PMID- 14948393
TI  - Psychological control of the thumb sucking problem.

PMID- 14948394
TI  - Lifelong adjustment of man and job; the possible role of multiphasic screening.

PMID- 14948395
TI  - A study of diagnostic errors in clinicopathological conferences at the
      Massachusetts General Hospital during a 25 year period.

PMID- 14948396
TI  - Bay area syndromes.

PMID- 14948397
TI  - Anorexia nervosa an unusual case study.

PMID- 14948398
TI  - [Rhythmic properties of skeletal muscle in relation to other rhythmic phenomena].

PMID- 14948399
TI  - [Formation of rhythms in frequent excitation of skeletal muscle].

PMID- 14948400
TI  - [Galvanic waving of muscles (Kuehne) in relation to the problem of rhythm].

PMID- 14948402
TI  - [Investigation of causes of rhythms and periods on a catalytic model].

PMID- 14948401
TI  - [Interference causing periodic movements of the frog stomach].

PMID- 14948403
TI  - [Connection between registration and objective facts in irritation of the
      vestibular apparatus by alternating current and optokinetic pendulant irritation
      of the retina].

PMID- 14948404
TI  - [Potentiometric determination of the oxygen pressure in whole blood with the
      mercury drip electrode; theory and practice].

PMID- 14948405
TI  - [Practice of potentiometric determination of oxygen pressure in whole blood].

PMID- 14948406
TI  - [Hemoxitensiometer; an apparatus for routine determination of oxygen pressure in
      whole blood].

PMID- 14948407
TI  - [A new tonometer for quick equilibration of blood with different partial gas
      pressures].

PMID- 14948408
TI  - [Determination of visual acuity and intensity with different colored glasses].

PMID- 14948409
TI  - [Effects of strychnin, urethar a and santonin on the electroretinogram of the
      frog under application of light of same energy and different wave length].

PMID- 14948410
TI  - [Extension potentials of the sartorius muscle and the myocardium of the frog].

PMID- 14948411
TI  - [Threshold of irritability and conduction speed of the frog nerve under
      carbondioxide application].

PMID- 14948412
TI  - [Investigations on the duration of the silent period after monosynaptic reflexes
      (proprioceptive reflex) and after antidromic stimulation].

PMID- 14948413
TI  - [Capillarisation of the brain under the influence of insulin].

PMID- 14948414
TI  - [Action currents in centrifugal cardiac nerves].

PMID- 14948415
TI  - [Effects of climate in high altitude on number of blood platelets and on fibrin
      retraction].

PMID- 14948416
TI  - [Adrenalinogen blood level and adrenal cortical hormone; experiments on torpedo].

PMID- 14948417
TI  - [Determination of loco-motor activity of mice by mechanical rectifier].

PMID- 14948418
TI  - [The isolated diaphragm strip with natural innervation; a new method to determine
      the reaction of the respiratory center].

PMID- 14948419
TI  - [Determination of adequate stimulus for thermoreceptors].

PMID- 14948420
TI  - [Permeability of the lens capsule].

PMID- 14948421
TI  - [Irritability & effects of electrical irritation of heart nerves].

PMID- 14948422
TI  - [Role of glucose and potassium in the muscle reaction; investigations on the
      isolated diaphragm of normal and adrenalectomized rats].

PMID- 14948423
TI  - [Effects of 1-adrenalin and 1-arterenol on the oxygen consumption of the relaxing
      skeletal muscle].

PMID- 14948424
TI  - [Oxygen consumption of the relaxing skeletal muscle in reflectory
      vasoconstriction].

PMID- 14948425
TI  - [Partition of function in the visual organ].

PMID- 14948426
TI  - [Effects of the cochlear nerve on the tonus of the striated skeletal muscle of
      the frog].

PMID- 14948427
TI  - [The optimal horopter; attempt to interprete the subjective celestial curvature].

PMID- 14948428
TI  - [Difference of renal vascular reactions from vascular reactions of other parts of
      the body].

PMID- 14948429
TI  - [Circulatory effects of insulin].

PMID- 14948430
TI  - [Cold tremor and periodicity of amplitudes in cats].

PMID- 14948431
TI  - [Artificial changes of the interruption tolerance in the vascular system of
      striated muscle].

PMID- 14948432
TI  - [Arteriovenous oxygen difference in various neural and humoral increases of blood
      supply].

PMID- 14948433
TI  - [Effects of pulmonary emphysema on the oxygen consumption of the heart-lung
      preparation].

PMID- 14948434
TI  - [Energetics of the normal and hypertrophied isoled mammalian heart].

PMID- 14948435
TI  - [The role of the adrenal glands and the pituitary in regulation of the blood
      concentration].

PMID- 14948436
TI  - [Motion parallactic monocular depth impression].

PMID- 14948437
TI  - [Respiration of striated muscles of cold blooded animals in acetycholine
      contraction and in tetany].

PMID- 14948438
TI  - [A small irritation apparatus for laboratory and instruction purpose].

PMID- 14948439
TI  - [The double masseteric preparation].

PMID- 14948440
TI  - [Investigations on the Gildemeister effect of alternating currents of medium
      frequency].

PMID- 14948441
TI  - [Interior mechanics of pennated muscles].

PMID- 14948442
TI  - [Hypertrophy of retinal vessels during chronic hypoxia in rabbits].

PMID- 14948443
TI  - [Increase of irritability of arteries and angiospasm after local damaging of
      tissue].

PMID- 14948444
TI  - [Determination of the cation content of the mammalian muscle fiber under normal
      and pathological conditions].

PMID- 14948445
TI  - The significance of the anion in active salt uptake by isolated frog skin.

PMID- 14948446
TI  - [Wave of difference of the cold- and worm sensation in relation to the absolute
      temperature of air and skin].

PMID- 14948447
TI  - [Proteins of the peripheral nerve].

PMID- 14948448
TI  - Stimulation and elimination of the anterior thalamic nuclei in man and cat.

PMID- 14948449
TI  - [Sensual sensation, perception & illusion].

PMID- 14948450
TI  - Experimental contribution to the duplicity theory of consciousness and
      perception.

PMID- 14948451
TI  - [Dissolution of novocaine preparations].

PMID- 14948452
TI  - [Paperchromatographic demonstration of natural cumarins in plants; cumarins of
      pimpinella magna and pimpinella saxifraga. IV. Communication of
      paperchromatography in phytochemical analysis].

PMID- 14948453
TI  - [Production of injectio calcii laevulinatis 10%].

PMID- 14948454
TI  - [Redox systems on pharmacy].

PMID- 14948455
TI  - [Alkaloids of colchicum automonale during its development substances of colchicum
      autumale and their derivatives].

PMID- 14948456
TI  - [Demineralization of water by ion transfer].

PMID- 14948457
TI  - [Investigations on linimentum calcis Ph. H. V..].

PMID- 14948458
TI  - [Acid base titration in anhydrous solutions and pharmaceutical applications].

PMID- 14948459
TI  - [The Belgian pharmacopeias].

PMID- 14948460
TI  - [A Netherlands Indian pharmacopeia].

PMID- 14948461
TI  - [Fat emulsions for intravenous administration].

PMID- 14948462
TI  - [Detection of arsenic in mercury compounds].

PMID- 14948463
TI  - [The pharmaceutic aspects of the poem De Moffeschans by Petrus Hondius;
      contribution to the history of herb culture in Netherlands].

PMID- 14948464
TI  - [Hexamethonium salts in hypertension].

PMID- 14948465
TI  - [Proposed law for dispensation of therapeutic agents. Proposed drug law].

PMID- 14948466
TI  - [Address of the States General in the second chamber].

PMID- 14948467
TI  - [Violation of article 8 of the pharmacy law].

PMID- 14948468
TI  - [Contrast media].

PMID- 14948469
TI  - [Jan van Riebeeck in the development of pharmacy in the Cape Colony].

PMID- 14948470
TI  - In memoriam M den Heijer.

PMID- 14948471
TI  - [Analeptics].

PMID- 14948472
TI  - [Paper chromatography of ergotoxine and ergotinine; preliminary report].

PMID- 14948473
TI  - [The proposed law on drug distribution; critique by the drug manufacturers].

PMID- 14948474
TI  - [New investigations on azulenes and azulene formators].

PMID- 14948475
TI  - [Physiology and pathology of food with special respect to vitamins].

PMID- 14948476
TI  - [Lupulon and humulon, their antibacterial effects and therapeutic use in
      tuberculous infections].

PMID- 14948477
TI  - [Veterinarian and pharmacopeia].

PMID- 14948478
TI  - [Production of extractum belladonnae].

PMID- 14948479
TI  - [The Brassica factor and other thyroid antagonists as a cause for goiter].

PMID- 14948480
TI  - [The beta-carotene content of the carrot, Daucus carota L].

PMID- 14948481
TI  - [Analytic study on Silybum Marianum Gaertner].

PMID- 14948482
TI  - [Effects of different ways of exsiccation on the content of azulogenic substances
      in Flores Chamomillae. I..].

PMID- 14948483
TI  - [Pharmacology of cortex Piscidae].

PMID- 14948484
TI  - [The 1951 Meeting of the German Society for Fat Science e.V].

PMID- 14948485
TI  - [Quantitative colorimetric determination of p-aminobenzyldiethylaminoethanol
      hydrochloride (Jenacain, novocain, procain) and p-aminobenzoic acid].

PMID- 14948486
TI  - [New apparatus in determination of etheric oils in drugs].

PMID- 14948487
TI  - [A new vehicle for suppositories].

PMID- 14948488
TI  - [Prophylaxis and therapy of mosquito bites].

PMID- 14948489
TI  - [Food and need of food].

PMID- 14948490
TI  - [Importance of choline in pharmacology for cholesteria and fat metabolism].

PMID- 14948491
TI  - [50 years naphthalan].

PMID- 14948492
TI  - [Galenos (Galen) and galenica].

PMID- 14948493
TI  - [The desiccation ration of a few pharmaceutical and spice plants].

PMID- 14948494
TI  - [Changes of content of azulogenic substances in the blossoms of Matricaris
      chamomilla L. during the day. II..].

PMID- 14948495
TI  - [Self mutilation with Rhizoma Hellebori nigri].

PMID- 14948496
TI  - [Rhus toxidendron L the poison tree-sumach].

PMID- 14948497
TI  - [Adonis vernalis].

PMID- 14948498
TI  - [Right of use of developments and inventions performed in government or public
      institutions].

PMID- 14948499
TI  - [Work meeting of the German Chemists in Leipzig, October 17-20, 1951].

PMID- 14948500
TI  - [Testing of drugs against pernicious anemia].

PMID- 14948501
TI  - [Pharmacology and clinical use of cobalt].

PMID- 14948502
TI  - [Effects of active substances of white thron. I].

PMID- 14948503
TI  - [Prophylaxia and therapy of insect bites. II].

PMID- 14948505
TI  - [Comments to the 7th edition of the German pharmacopeia].

PMID- 14948504
TI  - [Clinical and pharmacological comments to the new German pharmacopeia].

PMID- 14948506
TI  - [Fast method of pure solutions for injection in a hospital].

PMID- 14948507
TI  - [Food stuffs and need for it. II].

PMID- 14948508
TI  - [Chemical and physiologic reactions in digestion].

PMID- 14948509
TI  - [Prophylaxis of dental caries and pharmacist].

PMID- 14948510
TI  - [Active components of allium sativum L].

PMID- 14948511
TI  - [Successful planting of Helianthus tuberosus L].

PMID- 14948512
TI  - [Nicandra physaloides L. Gaertner].

PMID- 14948513
TI  - Surgical experiences in urinary lithiasis; a review of 452 operated cases.

PMID- 14948514
TI  - Bleeding after the age of menopause.

PMID- 14948515
TI  - Mortality following gynecological surgery.

PMID- 14948516
TI  - Eight consecutive cases of radical neck dissection.

PMID- 14948517
TI  - Surgery of non medical gall bladder disease.

PMID- 14948518
TI  - Transurethral resection in the female.

PMID- 14948519
TI  - An easier technique of applying forceps on the head in right occipito anterior
      and right occipito transverse positions.

PMID- 14948520
TI  - DOCTOR Victor Sevilla.

PMID- 14948521
TI  - Osteotomy of the spine; a report of two cases.

PMID- 14948522
TI  - Gastric ulcer and its relation to cancer; report of cases.

PMID- 14948523
TI  - Advantages of dual plating in fractures of long bones.

PMID- 14948524
TI  - Surgical conditions in gynecology and obstetrics.

PMID- 14948525
TI  - A modified reduction of temporo-mandibular joint dislocation.

PMID- 14948526
TI  - An exercise program for axillary nerve injuries.

PMID- 14948527
TI  - Camping for crippled children. I. Organization of a physical therapy program.

PMID- 14948528
TI  - Camping for crippled children. II. Organization and administration.

PMID- 14948529
TI  - A new design in parallel bars.

PMID- 14948530
TI  - Probable cause of low back pain among bus drivers.

PMID- 14948531
TI  - Heating the knee joint.

PMID- 14948532
TI  - Some trends in reconstructive surgery.

PMID- 14948533
TI  - The use of posterior one-stage pedicle flaps of the lower leg.

PMID- 14948534
TI  - Survival and utilization of cadaver skin.

PMID- 14948535
TI  - Successful homotransplantation of skin from mother to daughter.

PMID- 14948536
TI  - The use of the Kirschner pin in fractures of the condyle.

PMID- 14948537
TI  - Skin plastic for ureteral diversion.

PMID- 14948538
TI  - Correction of the wide nose with a pinch suture.

PMID- 14948539
TI  - Saddle nose; their treatment with the semilunar cartilage of the knee joint.

PMID- 14948540
TI  - Protruding ears; another method of treatment.

PMID- 14948541
TI  - Avulsion of ring finger skin.

PMID- 14948542
TI  - Squamous cell carcinoma in children.

PMID- 14948543
TI  - A new skin hook.

PMID- 14948544
TI  - [Blood coagulation of portal hypertensives subjected to spleno renal
      anastomosis].

PMID- 14948545
TI  - [Streptomycin in experimental tuberculosis of the guinea pig; histopathological
      study].

PMID- 14948546
TI  - [Vitamin B6 in its effect on vomiting caused by ether narcosis does not affect
      the bulbar emetic center; experimental study].

PMID- 14948547
TI  - [Macrophagic and colloidopexic capacity after pulmonary exeresis].

PMID- 14948548
TI  - [Heparin therapy and wound healing process].

PMID- 14948549
TI  - [Ultrasonics in wound healing].

PMID- 14948550
TI  - [Morphological factors connected with over five-year survival following
      operations for gastric carcinoma; review of the macroscopic and histological
      criteria of prognostic evaluation and a definition of a particular type of low
      malignancy].

PMID- 14948551
TI  - [Papillostomy for permanent drainage of bile ducts].

PMID- 14948552
TI  - [Effect of synthetic sympathomimetic drug (methedrin) in the prevention and
      treatment of operative shock].

PMID- 14948553
TI  - [A case of cavernous angioma of the liver].

PMID- 14948554
TI  - [Conditioned syndromes and the main general processes].

PMID- 14948555
TI  - [Anamnestic antecedents in blood diseases].

PMID- 14948556
TI  - [Capillary rish in various hemorrhagic diseases].

PMID- 14948557
TI  - [Modern views on the treatment of obesity].

PMID- 14948558
TI  - [Chloramphenicol therapy of Q fever].

PMID- 14948559
TI  - [Simple modification of sphygmomanometers and oscillometers].

PMID- 14948560
TI  - [Cholangiography and pre-operative manometry in biliary tract surgery].

PMID- 14948561
TI  - [Introduction to constitutional pathology].

PMID- 14948562
TI  - [Effect of isonicotinic acid hydrazide on intracutaneous infection caused by
      streptomycin-sensitive and streptomycin-resistant Koch Bacilli in guinea pigs].

PMID- 14948563
TI  - [Diaphragmatic hernia and anemia].

PMID- 14948564
TI  - [Broncho graphic examinations in broncho-pulmonary tuberculosis].

PMID- 14948565
TI  - [Physical and experimental education of infant and children].

PMID- 14948566
TI  - [Nitrogen mustard in rheumatoid arthritis].

PMID- 14948567
TI  - [Urological hypertension].

PMID- 14948568
TI  - [Diagnosis of active tuberculosis].

PMID- 14948569
TI  - [Antitubercular therapy with the new derivatives of nicotinic acid].

PMID- 14948570
TI  - [Abdominal syndrome from spider bite, simulating perforated gastric or duodenal
      ulcer].

PMID- 14948571
TI  - [Galactorrhea after thoracoplasty].

PMID- 14948572
TI  - [Recent American data on isonicotinic acid hyprazide].

PMID- 14948573
TI  - [Some criteria of discrimination between endocranitis, endocraniosis and mixed
      forms].

PMID- 14948574
TI  - [A case of Pelger-Huet's anomaly].

PMID- 14948576
TI  - [Bill for the establishment of the Ministry of Hygiene and Public Health].

PMID- 14948575
TI  - [Congenital diaphragmatic hernia of the right lobe of the liver simulating
      intrathoracic tumor].

PMID- 14948577
TI  - [Diagnosis of parathyroid diseases].

PMID- 14948578
TI  - [A case of Q fever, probably the first in the province of Padua].

PMID- 14948579
TI  - [Radiological diagnosis of peptic ulcer].

PMID- 14948580
TI  - [First case of indigenous visceral Leishmaniasis in Romagna].

PMID- 14948581
TI  - [Alterations in the morphology and permeability of the capillaries in acute
      articular rheumatism].

PMID- 14948582
TI  - [Treatment of gastro-duodenal perforations and hemorrhage].

PMID- 14948583
TI  - [A new apparatus for electrophoresis on filter paper].

PMID- 14948584
TI  - [Treatment of osteoarticular tuberculosis with combined streptomycin, PAS and
      vitamins A and D3].

PMID- 14948585
TI  - [Current clinical, etiopathological and therapeutic aspects of pernicious
      anemia].

PMID- 14948586
TI  - [Early changes in cutaneous allergy in tubercular subjects treated with
      isonicotinic acid hydrazide].

PMID- 14948587
TI  - [Clinical and experimental tests of the rectal use of combined calcium, balsamic
      and vitamin substances].

PMID- 14948588
TI  - [Angiographic diagnosis of thrombosis of the internal carotid artery or of its
      branches].

PMID- 14948589
TI  - [A case of cystic pneumatosis of the intestine; etiopathological and clinical
      study].

PMID- 14948590
TI  - [Pneumocisternographic evidence in optic-chiasmatic arachnoiditis].

PMID- 14948591
TI  - [Relations between anti-anemic factors and chain reactions: a new aspect of
      anemia therapy].

PMID- 14948592
TI  - [Biorhythm of urinary elimination of 17-ketosteroids; clinical value of
      research].

PMID- 14948594
TI  - [Equalization of the national medico-surgical tax rates].

PMID- 14948593
TI  - [Non-surgical treatment of perforated gastro-duodenal ulcer].

PMID- 14948595
TI  - [Pathogenesis and therapy of arterial hypertension].

PMID- 14948596
TI  - [A case of incomplete double urethra].

PMID- 14948597
TI  - [Synthetic organic insecticide poisoning].

PMID- 14948598
TI  - [Hereditary factors in the pathogenesis of pernicious anemia].

PMID- 14948599
TI  - [Recklinghausen's neurofibromatosis with malignant evolution].

PMID- 14948600
TI  - [Modern fundamentals of the pathology of the vegetative nervous system].

PMID- 14948601
TI  - [Fractures of the mandible treated with continuous elastic traction].

PMID- 14948602
TI  - [Richet and the discovery of anaphylaxis].

PMID- 14948603
TI  - [Psychotic oculomotor attacks and Pavlov's neurodynamic localization theory].

PMID- 14948604
TI  - [A simplified method of electrophoresis for clinical application].

PMID- 14948605
TI  - [Treatment of cerebral embolism in heart diseases by anticoagulants; heparin and
      derivatives of coumarin].

PMID- 14948606
TI  - [Prolonged sleep therapy in functional speech disorder].

PMID- 14948607
TI  - [Treatment of scalds with gentian violet].

PMID- 14948608
TI  - [A case of five months' ovarian pregnancy].

PMID- 14948609
TI  - [A case of acute, extensive phlegmon of the stomach].

PMID- 14948610
TI  - [A case of paratyphoid B complicated by perforation of the ileum and acute
      obstruction, treated surgically with good result].

PMID- 14948611
TI  - [The work of I P Pavlov and his school in the field of experimental pathology].

PMID- 14948612
TI  - [Proteolytic enzymes of blood serum and their inhibitors].

PMID- 14948613
TI  - [Early diagnosis of cancer of the nipple of breast].

PMID- 14948614
TI  - [Illness among members of health insurance and their family in 1949].

PMID- 14948615
TI  - [Electrokymographic tracing of the left ventricular systole].

PMID- 14948616
TI  - [Incomplete atrio-ventricular block].

PMID- 14948617
TI  - [Basis of treatment in diabetes].

PMID- 14948618
TI  - [Rare cardiac complications of thromboangiitis obliterans].

PMID- 14948619
TI  - [Spontaneous rupture of the stomach].

PMID- 14948620
TI  - [An unusual case if fibroma of the vulva].

PMID- 14948621
TI  - [Individuality of blood characteristics].

PMID- 14948622
TI  - [Histophysiology of parathyroids in mammals].

PMID- 14948623
TI  - [Dystonia of the biliary tract and its surgical treatment].

PMID- 14948624
TI  - [Hormone therapy of metastasis of cancer of the nipple to bone].

PMID- 14948625
TI  - [Effect of tobacco smoke on systemic vitamin C level].

PMID- 14948626
TI  - [Diseases of connective tissue with a special reference to systemic lupus
      erythematosus and scleroderma].

PMID- 14948627
TI  - [Electrokymographic tracing of the left ventricular systole].

PMID- 14948628
TI  - [Quantitative method in comparative histopathology].

PMID- 14948629
TI  - [Stenosis of the splenic vein in a 9-year old girl].

PMID- 14948630
TI  - [Effect of slight post-insulin hypoglycemia on trichinosis].

PMID- 14948631
TI  - [A case of spontaneous pneumocranium after fracture of frontal bone].

PMID- 14948633
TI  - [A method to isolate the influenza pathogen].

PMID- 14948632
TI  - [A case of adiposis dolorosa treated with urethane].

PMID- 14948634
TI  - [The non-cellular forms of life, according to Lepeszynska and Grawitz].

PMID- 14948635
TI  - [Diagnostic value of cardiac catheterization].

PMID- 14948636
TI  - [Results of contemporary treatment of bacterial endocarditis].

PMID- 14948637
TI  - [Post-cholecystectomy syndrome].

PMID- 14948638
TI  - [Acquired hemolytic anemia].

PMID- 14948639
TI  - [Simplified method of determining the value of QT interval in
      electrocardiograms].

PMID- 14948640
TI  - [Non-cellular forms of life, according to Lepeszynska and Grawitz].

PMID- 14948641
TI  - [Role of the nervous system in allergic phenomena].

PMID- 14948642
TI  - [Mechanism of action of transfused blood and some surgical indications of blood
      transfusion].

PMID- 14948643
TI  - [Dependence of cardiogram on the spatial position of the heart].

PMID- 14948644
TI  - [The course and clinical forms of tuberculosis in man].

PMID- 14948645
TI  - [Management of preinvasive cancer of uterine cervix].

PMID- 14948646
TI  - [Radiological kymography and cinematography].

PMID- 14948647
TI  - [The Milk Bank in Krakow].

PMID- 14948648
TI  - [Effect of nicotinamide on endocrine glands].

PMID- 14948649
TI  - [Results of anticoagulant treatment of myocardial infarct].

PMID- 14948650
TI  - [Neurological complications of antityphoid vaccination].

PMID- 14948651
TI  - [Opsomyoclonic syndrome with cerebellar ataxia following pertussis encephalitis
      in a three-year-old].

PMID- 14948652
TI  - [Two cases of hydronephrosis].

PMID- 14948653
TI  - [Two cases of congenital dilatation of the urethra].

PMID- 14948654
TI  - [Surgical treatment of gastric and duodenal ulcer].

PMID- 14948655
TI  - [The Milk Bank in Krakow].

PMID- 14948656
TI  - [Report of the Institute of Pathological Anatomy of the Academy of Medicine in
      Lodz for the academic year 1950-51].

PMID- 14948657
TI  - [Application of the new group characteristics to establishing of paternity].

PMID- 14948658
TI  - [A quick method for determination of streptomycin sensitivity of tubercle
      bacilli].

PMID- 14948659
TI  - [Comparative study of biological methods of determination of vitamin B12].

PMID- 14948660
TI  - [Pulmonary infarctions].

PMID- 14948661
TI  - [General aplasia of the bone marrow (panmyelophthisis)].

PMID- 14948662
TI  - [The newest antituberculosis antibiotics].

PMID- 14948663
TI  - [Centenary of birth of Dr. Samuel Goldflam].

PMID- 14948664
TI  - [Report of the Institute of Pathological Anatomy of the Academy of Medicine in
      Warsaw, during the academic year 1950-51].

PMID- 14948665
TI  - [Pathogenesis and early diagnosis of uterine cancer].

PMID- 14948666
TI  - [Clinical observations on penicillin treatment of thyrotoxicosis].

PMID- 14948667
TI  - [Effect of technique of blood collecting on reaction of Biernacki].

PMID- 14948668
TI  - [Infection with yellow typhoid bacillus].

PMID- 14948669
TI  - [Closed traumatic injuries of the liver].

PMID- 14948670
TI  - [Numeric and clinical characteristics of late symptomatic syphilis].

PMID- 14948671
TI  - [Food poisoning].

PMID- 14948672
TI  - [Report of the II post-war Congress of Anatomists and Anatomopathologists;
      simultaneous IX congress of the members of Polish Anatomical Society].

PMID- 14948673
TI  - Experiences with the vaginal smear; report of a six year study.

PMID- 14948674
TI  - Surgical treatment of cancer of the colon and rectum; mortality and results in
      306 patients treated from 1930 to 1946.

PMID- 14948675
TI  - Some questions in differential diagnosis of rheumatism; report of three cases.

PMID- 14948676
TI  - [Cruveilhier-Baumgarten syndrome; case report].

PMID- 14948677
TI  - [Case of progressive pernicious anemia (medullary megaloblastosis with absence of
      Castle's intrinsic factor) with hydrochloric secretion maintained].

PMID- 14948678
TI  - [The structuration of social medicine].

PMID- 14948679
TI  - CONTROLLED hypotension.

PMID- 14948680
TI  - HIATUS hernia.

PMID- 14948681
TI  - The principles of chemotherapy.

PMID- 14948682
TI  - Progress in bacterial endocarditis.

PMID- 14948683
TI  - The role of lymphoid tissue and the adrenals in immunity.

PMID- 14948684
TI  - Fractures of the malar-zygomatic compound.

PMID- 14948685
TI  - Case of pyrexia of unknown origin.

PMID- 14948686
TI  - Spontaneous pneumoperitoneum; associated with Meckel's diverticulum.

PMID- 14948687
TI  - Physiologic principles of resuscitation and oxygen therapy.

PMID- 14948688
TI  - Treatment of brucellosis with aureomycin or terramycin combined with
      dihydrostreptomycin.

PMID- 14948689
TI  - Pneumoperitoneum in the treatment of pulmonary tuberculosis.

PMID- 14948690
TI  - The diagnostic significance of a lump in the neck.

PMID- 14948691
TI  - Ruptured cervical intervertebral disks.

PMID- 14948692
TI  - Undiagnosing coronary thrombosis.

PMID- 14948693
TI  - Early diagnosis and management of gastric lesions.

PMID- 14948694
TI  - The frequency of hepatitis in doctors.

PMID- 14948695
TI  - Management of resistant, nonhealing skin lesions.

PMID- 14948696
TI  - Artificial respiration.

PMID- 14948697
TI  - Subdural hematomas in infants.

PMID- 14948699
TI  - Allergic dermatoses due to drugs.

PMID- 14948698
TI  - Respiratory emergencies in the newborn.

PMID- 14948700
TI  - Acute cardiac failure.

PMID- 14948701
TI  - Clinical ballistocardiography.

PMID- 14948702
TI  - Physician to royalty.

PMID- 14948703
TI  - [Auxiliary external approach in surgical collapsotherapy].

PMID- 14948704
TI  - [New method of thoracoplasty].

PMID- 14948705
TI  - [Role of spirated capillary drainage in surgery of infectious conditions of the
      thoraco-abdominal region].

PMID- 14948706
TI  - [Recurrent, early acute cavitary distension following thoracoplasty].

PMID- 14948707
TI  - [Anti-histaminics and preservation of arterial grafts].

PMID- 14948708
TI  - [Case of goiter of the posterior mediastinum].

PMID- 14948709
TI  - [Segmental conservative resection of the pleura for chronic abscess].

PMID- 14948710
TI  - [Unusual pulmonary malformation; extrapleural lobe associated with venous
      anomaly].

PMID- 14948711
TI  - [Thirty commissurectomies for mitral stenosis].

PMID- 14948712
TI  - [Results of 24 commissurectomies for mitral stenosis].

PMID- 14948713
TI  - [Remaining cavity after pneumonectomy].

PMID- 14948714
TI  - [Exeresis of pulmonary metastatic tumors of the type of isolated peripheral
      mass].

PMID- 14948715
TI  - [Ten cases of pulmonary echinococcosis].

PMID- 14948716
TI  - [Pericardial coelomic cysts].

PMID- 14948717
TI  - [Acrylic plombage in pneumonectomy].

PMID- 14948718
TI  - [Technic of effacement of the remaining cavity after pneumonectomy].

PMID- 14948719
TI  - [Technic of decortication associated with total pneumonolysis in the treatment of
      non-tuberculous chronic pyothorax].

PMID- 14948720
TI  - [Surgical treatment of cavers of the inferior cavity].

PMID- 14948721
TI  - [Experience with inferior lobectomy in tuberculosis].

PMID- 14948722
TI  - [Juxta-hilar clear images of the lung; sequels of initial tuberculosis in
      children].

PMID- 14948723
TI  - [Treatment in stages of vestibular disorders caused by streptomycin].

PMID- 14948724
TI  - [Value of radiophotography as a medium in the systematic screening of thoracic
      diseases].

PMID- 14948725
TI  - [Fatal complication in extra-fascial plombage with polyethylene bags; extra
      fascial esophago-tracheal fistula].

PMID- 14948726
TI  - [Accidents due to rupture of periradicular arachnoid sheets in costovertebral
      disarticulation].

PMID- 14948727
TI  - [Pneumonectomies of destroyed tuberculous lungs].

PMID- 14948728
TI  - [Fibrothorax].

PMID- 14948729
TI  - [Bronchoesophageal fistula diagnosed in repeated lobectomy].

PMID- 14948730
TI  - [Limits of exploratory thoracotomy in pulmonary cancer].

PMID- 14948731
TI  - [Use of injections of plastic substances in anatomopathological studies of the
      lung].

PMID- 14948732
TI  - Some remarks on the connection between tilting reactions, past pointing and
      romberg's symptom in vertiginous patients.

PMID- 14948733
TI  - Laryngeal paralysis in surgery and diseases of the thyroid gland and their
      treatment.

PMID- 14948734
TI  - Probable polypous form of leishmaniasis of the nose.

PMID- 14948735
TI  - [Experimental principles of extra-labyrinthine surgery in Meniere's disease].

PMID- 14948736
TI  - [The neuro-muscular fascicles of the respiratory tract and the changes in
      tuberculosis].

PMID- 14948737
TI  - [Osteodysplasia fibrosa deformans juvenilis of the right half of the skull].

PMID- 14948738
TI  - [Not Available].

PMID- 14948739
TI  - Climate and the distribution of disease.

PMID- 14948741
TI  - Body temperature and its control.

PMID- 14948740
TI  - Climate as a therapeutic agent.

PMID- 14948742
TI  - The deleterious effects of exposure to tropical environments.

PMID- 14948743
TI  - The effects of excessive cold and their treatment.

PMID- 14948744
TI  - The ideal home; optimum living conditions in temperate climates.

PMID- 14948745
TI  - ISONICOTINIC acid hydrazide.

PMID- 14948746
TI  - Frequency and dysuria in the female.

PMID- 14948747
TI  - Practical problems of high protein feeding.

PMID- 14948748
TI  - Mrs. Beeton's predecessor William Kitchiner, M.D. (c. 1775-1827).

PMID- 14948749
TI  - Coronary dilators.

PMID- 14948750
TI  - Metrorrhagia.

PMID- 14948751
TI  - Early pulmonary tuberculosis and the general practitioner.

PMID- 14948752
TI  - The clinical assessment of cardiac efficiency.

PMID- 14948753
TI  - The treatment of cardiac arrhythmias.

PMID- 14948754
TI  - Heart disease as a cause of sudden death.

PMID- 14948755
TI  - The surgery of the heart and great vessels.

PMID- 14948756
TI  - The practical value of cardiac catheterization.

PMID- 14948757
TI  - Heart disease in pregnancy.

PMID- 14948758
TI  - Nicotinamide and pellagra; a review of the development of knowledge and of the
      present position.

PMID- 14948759
TI  - Social and medical aspects of tattooing.

PMID- 14948760
TI  - Intravenous iron treatment in general practice.

PMID- 14948762
TI  - Useful manipulations in general practice.

PMID- 14948761
TI  - An hypothesis relating to the renal circulation in acute nephritis.

PMID- 14948763
TI  - The chemotherapy of tuberculosis.

PMID- 14948764
TI  - Isonicotinic acid hydrazide and tuberculosis; a provisional assessment.

PMID- 14948765
TI  - DIAGNOSTIC significance of cyanosis.

PMID- 14948766
TI  - TREATMENT of fibrositis.

PMID- 14948767
TI  - [Antiepidemic measures against infantile paralysis].

PMID- 14948769
TI  - [Management of patient suspected of poliomyelitis].

PMID- 14948768
TI  - [Diagnosis and treatment of poliomyelitis].

PMID- 14948770
TI  - [Early diagnosis of poliomyelitis].

PMID- 14948771
TI  - [Differential diagnosis of infantile paralysis].

PMID- 14948772
TI  - [Treatment of infantile paralysis of the acute stage].

PMID- 14948773
TI  - [Treatment of infantile paralysis in the stage of convalescence].

PMID- 14948774
TI  - [Poliomyelitis; certain problems].

PMID- 14948775
TI  - [Viral encephalitis].

PMID- 14948776
TI  - [Certain unusual vascular diseases].

PMID- 14948777
TI  - [Experiences in the Makarova hospital].

PMID- 14948778
TI  - [Importance of traumatic surgery with special reference to facial injuries].

PMID- 14948779
TI  - [Cooperation of pediatrician and general practitioner with plastic surgeon].

PMID- 14948781
TI  - [Certain aspects of diagnosis and first aid in injuries of the jaws].

PMID- 14948780
TI  - [Principles in management of facial injuries].

PMID- 14948782
TI  - [Closed fractures of the facial bones].

PMID- 14948783
TI  - [Facial injuries with a loss of tissue].

PMID- 14948784
TI  - [Modern means of prevention of neural diseases].

PMID- 14948785
TI  - [New form of health services in Czechoslovakia].

PMID- 14948786
TI  - [Organization of public health in Czechoslovakia].

PMID- 14948787
TI  - [Bornholm disease; Coxsackie virus infection; summer devil's grip; epidemic
      myalgia].

PMID- 14948788
TI  - [Sneezing and coughing in children].

PMID- 14948789
TI  - [Control of whooping cough].

PMID- 14948790
TI  - [Diagnosis of jaundice].

PMID- 14948792
TI  - [Surgical indications in hypospadias].

PMID- 14948791
TI  - [Sexual aspects of hypospadias].

PMID- 14948794
TI  - [Neonatal mortality].

PMID- 14948793
TI  - [Prevention of respiratory infections in newborn].

PMID- 14948795
TI  - [Preventive and therapeutic dental care in school children].

PMID- 14948796
TI  - [Education of rural physicians].

PMID- 14948797
TI  - [Therapeutic use of radioactive isotopes].

PMID- 14948798
TI  - [Clinical determination of urinary proteins].

PMID- 14948799
TI  - [Chronic diarrhea; causes and therapeutic considerations].

PMID- 14948800
TI  - [Neurocirculatory asthenia; consideration on etiology and pathogenesis].

PMID- 14948801
TI  - [Protamine-zinc-insulin in combination protamine-zinc-insulin with ordinary
      insulin in ambulatory treatment of diabetes mellitus].

PMID- 14948802
TI  - [Health education in the Soviet Union in the struggle for health in the
      population].

PMID- 14948803
TI  - [Unilateral total harelip; experience with Mesurier's technic].

PMID- 14948804
TI  - [Studies on parasitic diseases of the female genital tract].

PMID- 14948805
TI  - [Hepatic contusions and wounds].

PMID- 14948806
TI  - [Therapeutic and diagnostic significance of iron gluconate in secondary anemias].

PMID- 14948807
TI  - [Dietetic therapy of liver diseases].

PMID- 14948808
TI  - [Struma ovarii].

PMID- 14948809
TI  - [Transabdominal cholangiography].

PMID- 14948810
TI  - [Intraspinal carbon dioxide in children; history, scientific bases, technic and
      method].

PMID- 14948811
TI  - [Therapeutic progress in internal medicine in 1951; respiratory apparatus and
      tuberculosis].

PMID- 14948812
TI  - [Spontaneous hernia of the lung].

PMID- 14948813
TI  - [Spontaneous biliobiliary fistulas].

PMID- 14948814
TI  - [Right and left ventricular extrasystoles; electrocardiographic diagnosis].

PMID- 14948815
TI  - [Pseudotuberculous clinical and radiological manifestations in an epidemic of
      psittacocis].

PMID- 14948816
TI  - [Metrorrhagia and anesthesia of the superior sympathetic cervical ganglion].

PMID- 14948817
TI  - [Action on hexamethonium bromide on arterial hypertension].

PMID- 14948818
TI  - [Hereditary of breast cancer; familial history of 500 cases of breast cancer].

PMID- 14948819
TI  - [Experience with the treatment of various clinical forms of eczema with cortisone
      and corticotrophin].

PMID- 14948820
TI  - [Inefficacy of pregnenolone in maintaining remission obtained with cortisone in
      rheumatoid arthritis].

PMID- 14948821
TI  - [Acute volvulus of the sigmoid colon].

PMID- 14948822
TI  - [Stenosing lymphosarcoma; clinical observation].

PMID- 14948823
TI  - [Infectious rheumatism and prostatovesiculitis].

PMID- 14948824
TI  - [Therapeutic progress in the field of internal medicine in 1951; hepatology].

PMID- 14948825
TI  - [Injuries of the peripheral nerves during the war].

PMID- 14948826
TI  - [Surgery of leg ulcer].

PMID- 14948827
TI  - [Treatment of post-phlebitic varicose ulcers].

PMID- 14948828
TI  - [Treatment of post-phlebitic and other leg ulcers].

PMID- 14948829
TI  - [Pathogenesis and treatment of leg ulcers].

PMID- 14948830
TI  - [Treatment of leg ulcers; conclusions].

PMID- 14948831
TI  - [Examination of fecal material].

PMID- 14948832
TI  - [Bases for diagnosis of hepatopathies and hepatic insufficiency].

PMID- 14948833
TI  - [Considerations on strangulated hernia].

PMID- 14948835
TI  - [Surgical indications in gastroduodenal ulcer].

PMID- 14948834
TI  - [Hereditary hemorrhagic telangiectasis or Rendu-Osler disease; clinical
      importance].

PMID- 14948836
TI  - [Pulmonary suppuration and hyaluronidase].

PMID- 14948837
TI  - [Florescent microscopy of hydatid cyst].

PMID- 14948838
TI  - [Experience with tromexan].

PMID- 14948839
TI  - [Psychogenic aspects of skin diseases].

PMID- 14948840
TI  - [Pericranial hematoma].

PMID- 14948841
TI  - [Lithiasis of intrahepatic bile ducts].

PMID- 14948842
TI  - [Peritoneal gelatinous carcinoma].

PMID- 14948843
TI  - [Incision in the treatment of umbilical hernia].

PMID- 14948844
TI  - [Besnier's eczemato-licnenous pruritus (atopic dermatitis) with Andogsky's
      dermatogenous cataract; second observation in Argentina].

PMID- 14948845
TI  - [Treatment of leprosy with thiosemicarbazones].

PMID- 14948846
TI  - [Treatment of allergic diseases with adrenal hormones].

PMID- 14948847
TI  - [Treatment of chronic bronchial asthma with ACTH and cortisone].

PMID- 14948848
TI  - [Insulin resistance; comments on a new observation].

PMID- 14948849
TI  - [Progress in the field of neurology].

PMID- 14948850
TI  - [New sphincter in Taenia Saginata (Goeze, 1782)].

PMID- 14948851
TI  - [Diagnosis of chronic gastritis].

PMID- 14948852
TI  - [Succinic acid and anoxia].

PMID- 14948853
TI  - [Surgery of Parkinson's disease].

PMID- 14948854
TI  - [Surgical method in lithiasis of the hepatic bile ducts; extraction of calculi
      embedded in the common bile duct and in the papilla].

PMID- 14948855
TI  - [Generalized osteosclerosis secondary to prostatic carcinoma].

PMID- 14948856
TI  - [Roseola siphilitica nigricans; considerations on syphilitic pigmentation
      disorders].

PMID- 14948857
TI  - [Meningoencephalitis secondary to mumps; considerations on the origin of pyramido
      cerebello-labyrhinithic form].

PMID- 14948858
TI  - [Hepatostomy].

PMID- 14948859
TI  - [Functional renal insufficiency in intestinal obstruction].

PMID- 14948860
TI  - [Subarachnoid hemorrhage; therapy].

PMID- 14948861
TI  - [Bacterial endocarditis; therapy].

PMID- 14948862
TI  - [Possible role of sensitivity to homologous tissue products in the pathogenesis
      of rheumatoid arthritis].

PMID- 14948863
TI  - [Flatfoot; varieties and therapy].

PMID- 14948864
TI  - [Sims-Huhner or post-coitus test in sterility].

PMID- 14948865
TI  - [Studies on personality in hypertension by means of Rorschach test].

PMID- 14948866
TI  - [Fracassi's tractomy].

PMID- 14948867
TI  - [Role cobalt in hemopoiesis].

PMID- 14948868
TI  - [Presence of Salmonella and Shigella in intestines in dogs in Mexico City].

PMID- 14948869
TI  - [Action of paradione in epilepsy].

PMID- 14948871
TI  - [Surgical correction of rigid paralysis].

PMID- 14948870
TI  - [Treatment of pain in inoperable cancer of the cervix uteri].

PMID- 14948872
TI  - [Clinicopathological session; miliary tuberculosis with cirrhosis].

PMID- 14948873
TI  - [Q fever in Mexico].

PMID- 14948874
TI  - [Functional gastric dyspepsias].

PMID- 14948875
TI  - [Considerations on diagnosis of cestode infections].

PMID- 14948876
TI  - [Medical education in Mexico].

PMID- 14948877
TI  - [Anatomoclinical session; duodenal ulcer penetrating into the pancreas].

PMID- 14948878
TI  - [Cardiac insufficiency; physiopathological considerations].

PMID- 14948879
TI  - [Concept of pregnancy complications; treatment of eclampsia].

PMID- 14948880
TI  - [Responsibility of hospitals].

PMID- 14948881
TI  - [Clinicopathological session; chronic cholecystitis with chronic acute
      cholangitis, cause of death bronchopneumonia].

PMID- 14948882
TI  - [Contribution to the study of malnutrition in Yucatan children].

PMID- 14948883
TI  - [Clinical and public health aspects of acute respiratory infections in young
      children].

PMID- 14948884
TI  - [Chloramphenicol therapy of purulent meningitis].

PMID- 14948885
TI  - [Alleged bronchial adenomas as epitheliomas with modified stroma; identification
      of a bronchial tumor with myoepithelial cells].

PMID- 14948886
TI  - [Electroshock under phenacetylurea].

PMID- 14948887
TI  - [Mitral insufficiency in malignant rheumatism].

PMID- 14948888
TI  - [Subcutaneous injection of PAS in the presence of a factor of diffusion].

PMID- 14948890
TI  - [Malignant tumors of the bone in children].

PMID- 14948889
TI  - [Transfusion of washed or plasma free red cells].

PMID- 14948891
TI  - [Incoagulability of blood due to afibrinogenemia].

PMID- 14948893
TI  - [On poisoning by cheese in the Near and Middle East].

PMID- 14948892
TI  - [The practice of medicine by the clergy in the 17th century and Madame Fouquet's
      book of remedies].

PMID- 14948894
TI  - [Great significance of thyroid body auscultation in diagnosis of Bosow's
      diseases].

PMID- 14948895
TI  - [Anti-edema therapy associated with cellulicidal palliative chemotherapy of
      epithelial cancers].

PMID- 14948896
TI  - [Pathology and treatment of endocrine abortions].

PMID- 14948897
TI  - [Acute terminal ileitis and para B].

PMID- 14948898
TI  - [Wallenberg syndrome].

PMID- 14948899
TI  - [Trans-cutaneous ligature in surgery of varices].

PMID- 14948900
TI  - [Surgical significance of continuous registration of temperature in man].

PMID- 14948901
TI  - [Eczema and its treatment].

PMID- 14948902
TI  - [Statistics in medicine].

PMID- 14948903
TI  - [Faculty of Medicine of Paris, Chair of Medical Physical Chemistry; inaugural
      lecture].

PMID- 14948904
TI  - [General adaptation syndrome of H. Selye and the Reilly phenomenon].

PMID- 14948905
TI  - [Isonicotinic acid hydrazide in treatment of tuberculosis].

PMID- 14948906
TI  - [Possibilities, advantages and inconveniences of cytological diagnosis of
      cancers].

PMID- 14948907
TI  - [The Franco-Italian tunnel under Mont-Blanc and dangers of massive intoxication
      by carbon monoxide].

PMID- 14948908
TI  - [Alfredo Navarro (1868-1951)].

PMID- 14948909
TI  - [Well defined technic for right hepatectomy].

PMID- 14948910
TI  - [Semiological value of induced crystalluria test].

PMID- 14948911
TI  - [Bipolar arachnoiditis, edematous optic neuritis, and arachnoiditis of the
      pontocerebellar angle].

PMID- 14948912
TI  - [Some considerations on feminine hypertrichosis].

PMID- 14948913
TI  - [Hormones and men].

PMID- 14948914
TI  - [Bilharziasis from schistosoma haemotobium].

PMID- 14948915
TI  - [Leprosy and tuberculosis].

PMID- 14948916
TI  - [Robespierre and the insane].

PMID- 14948917
TI  - [Jacques Rouget, 1913-1952].

PMID- 14948918
TI  - [Distribution of urea in the body fluids].

PMID- 14948919
TI  - [Conservation of arteries; role of the laboratory and experimental results].

PMID- 14948920
TI  - [Fatal acute cerebropathy after treatment by streptomycin].

PMID- 14948921
TI  - [General pathological applications of recent data on arteriocapillary
      physiopathology].

PMID- 14948922
TI  - [Frequency of nephritic colic in acute abdomen].

PMID- 14948923
TI  - [Laboratory technics applied to the diagnosis of mumps].

PMID- 14948924
TI  - [For the rational utilization of the ancient School of Clinical Medicine in the
      Rue Des Saints-Peres].

PMID- 14948925
TI  - [Carcinoid of the gastrosplenic epiploon].

PMID- 14948926
TI  - [Effect of hepatic artery ligation on the portal system. II. Experimental study].

PMID- 14948927
TI  - [Thyroiditis and carcinoma; report of two cases].

PMID- 14948928
TI  - [Pagetic osteosis in the gouty and diabetic].

PMID- 14948929
TI  - [Opacification of the venous system of the skull and spine by the intramedullar
      route].

PMID- 14948930
TI  - [Surgical treatment of femoral foci in six cases of Albright's syndrome].

PMID- 14948931
TI  - [A stereotaxic study of the deep encephalic structures in man; technic;
      physiopathologic and therapeutic significance].

PMID- 14948932
TI  - [Left pancreatectomy for a cyst manifested solely by left subcostal pain and
      detected by aortography].

PMID- 14948933
TI  - [Subdural hydroma].

PMID- 14948934
TI  - [Radiology and nature].

PMID- 14948935
TI  - [Study of the reactions and the sensitivity of the biliary tract in hyperpressure
      tests in relation to the perfusion substances utilized (physiologic serum, bile
      from the patient and hydrosoluble iodized substances)].

PMID- 14948936
TI  - [The treatment of purulent effusions in extrapleural pneumothorax by local
      application of PAS].

PMID- 14948937
TI  - [Maximum respiration cycle test for the spirographic study of pulmonary
      ventilation].

PMID- 14948938
TI  - [Treatment of trachoma with terramycin].

PMID- 14948939
TI  - [Artificial hibernation in brain surgery].

PMID- 14948940
TI  - [On the cough reflex in lobotomized patients].

PMID- 14948942
TI  - [Trial labor].

PMID- 14948941
TI  - [A pure and painful form of nodose periarteritis].

PMID- 14948943
TI  - [Some important technical factors on the surgical excision of tuberculous
      pulmonary lesions].

PMID- 14948944
TI  - [Preliminary studies on the use of certain ganglioplegics in the treatment of
      acute cerebrovascular accidents].

PMID- 14948945
TI  - [Evaluation and clinical significance of phenol-steroids].

PMID- 14948946
TI  - [The role of the adrenal cortex in Reilly's phenomena; critical discussion of
      Selye's concept].

PMID- 14948947
TI  - [60 Cases of cancer of the esophagus and the upper part of the stomach; 30
      resections and total gastrectomies].

PMID- 14948948
TI  - [Critical study of allergy and immunity in spontaneous tuberculous infection and
      after BCG].

PMID- 14948949
TI  - [Potassium; physiopathological data].

PMID- 14948950
TI  - [On the fiftieth anniversary of the discovery of anaphylaxis].

PMID- 14948951
TI  - [Discovery of anaphylaxis].

PMID- 14948952
TI  - [The mechanism of anaphylaxis].

PMID- 14948953
TI  - [Charles Richet, 1850-1935].

PMID- 14948954
TI  - [Alimentary anaphylaxis].

PMID- 14948955
TI  - [Preinvasive cancer of the cervix uteri diagnosed by cervical smears and
      hysterography].

PMID- 14948956
TI  - [Apparatus for the continued extension of the neck].

PMID- 14948957
TI  - [Progressive vasoplegia during transfusion in post-shock vasomotor
      disequilibrium].

PMID- 14948958
TI  - [Intravenous urography in general practice].

PMID- 14948959
TI  - [Hormonology; its significance and contributions].

PMID- 14948960
TI  - [Study on microcythemias; reproduction of erythrocytes by budding; value of the
      fact of general pathology].

PMID- 14948961
TI  - [Significance of cerebral angiography as a method of diagnosis and localization
      of subtentorial intracranial hematomas; therapeutic inferences].

PMID- 14948962
TI  - [Tumoral syndrome of glomus jugulare].

PMID- 14948963
TI  - [A rare clinical encounter: venereal lymphogranuloma with malpighian cancer].

PMID- 14948964
TI  - [Cytodiagnosis of cancer of the stomach].

PMID- 14948965
TI  - [On primary amylosis].

PMID- 14948966
TI  - [Thalassemia and neurohemolytic syndromes].

PMID- 14948967
TI  - [Importance of tomography in the diagnosis of pulmonary tuberculosis].

PMID- 14948968
TI  - [The study of neoplastic cells in expectoration in bronchial cancer].

PMID- 14948969
TI  - [Pneumoencephalographic study of general paresis].

PMID- 14948970
TI  - [Papillary epithelioma of the ovary may reproduce the clinical picture of the
      Demons-Meigs' syndrome].

PMID- 14948971
TI  - [A radiological study of occlusion of the small intestine by appendicular
      abscess].

PMID- 14948972
TI  - [Radiography of the human body with radioactive isotopes].

PMID- 14948973
TI  - [Basic problems in control of tuberculosis in USSR].

PMID- 14948974
TI  - [Relationship between increased reactivity and resistance of the organism
      (allergy in immunity) in infectious process].

PMID- 14948975
TI  - [Studies on biological properties of Mycobacterium tuberculosis muris].

PMID- 14948976
TI  - [Standardization and study on the quality of dried BCG vaccine].

PMID- 14948977
TI  - [Method of determination of the resistance of Mycobacterium tuberculosis to
      antibiotics].

PMID- 14948978
TI  - [Possibility of diagnosis of tuberculosis by cerebral infection of white mice].

PMID- 14948979
TI  - [Methods of disinfection of laboratory containers from Mycobacterium
      tuberculosis].

PMID- 14948980
TI  - [Clinical aspects of early primary tuberculosis in school children].

PMID- 14948981
TI  - [Combined application of PAS and streptomycin in pulmonary tuberculosis in
      pulmonary surgical interventions].

PMID- 14948982
TI  - [Efficacy of the treatment of peculiarities of management of patients with
      artificial pneumothorax in climatic stations in mountains].

PMID- 14948983
TI  - [Results of laminar roentgenography-tomography in osteoarticular tuberculosis].

PMID- 14948984
TI  - [Surgical treatment of pulmonary tuberculosis at the Sverdlovsk hospital for
      railroad workers].

PMID- 14948985
TI  - [Clinical aspects of blood transfusion in pulmonary tuberculosis].

PMID- 14948986
TI  - [Anniversary conference of the Institute of Tuberculosis of the Academy of
      Medicine of USSR].

PMID- 14948988
TI  - FORENSIC science in the control of crime.

PMID- 14948987
TI  - [Third All-Russian conference on thoracic surgery].

PMID- 14948989
TI  - The functional organization of the central nervous system, an experimental
      analysis.

PMID- 14948990
TI  - CHICAGO Rheumatism Society.

PMID- 14948991
TI  - CHICAGO Society of Internal Medicine.

PMID- 14948992
TI  - Electron microscopy of Leptospiral strains.

PMID- 14948993
TI  - Influence of cortisone on experimental hypersensitivity and circulating antibody
      in the guinea pig.

PMID- 14948994
TI  - A phylogenetic study of the milk 'let-down' hormone.

PMID- 14948995
TI  - Effect of acetylcholine on mammary gland of the lactating sow.

PMID- 14948996
TI  - Source of secretion of milk 'let-down' hormone in domestic mammals.

PMID- 14948997
TI  - Effect of epinephrine and insulin on tissue electrolytes in normal and
      demedullated rats.

PMID- 14948998
TI  - The effect of diet on riboflavin and xanthine oxidase in rat liver and intestine.

PMID- 14948999
TI  - Growth of Newcastle disease virus in the embryonated egg.

PMID- 14949000
TI  - Response of the baby chich to West Nile virus.

PMID- 14949001
TI  - Further studies on antigenic variation of influenza A virus.

PMID- 14949002
TI  - Pharmacological studies on irradiated animals. II. Effect of cortisone on x-ray
      mortality of mice.

PMID- 14949003
TI  - Phage multiplication on two hosts. Isolation and activity of variants of
      staphylococcus phage P1.

PMID- 14949004
TI  - Soluble specific leptospiral complement-fixing antigens.

PMID- 14949005
TI  - Presence of a leukotaxine-like substance in extract of severely injured muscles.

PMID- 14949006
TI  - Efficacy of 1-ethanesulfonyl-4-ethyl-piperazine hydrochloride in treatment of
      controlled hemorrhagic shock.

PMID- 14949007
TI  - Platelets: VII. Shortened platelet survival time and development of platelet
      agglutinins following multiple platelet transfusions.

PMID- 14949008
TI  - Plasma proteins in venous and cord blood at delivery following uncomplicated and
      complicated pregnancies.

PMID- 14949009
TI  - Visualization of arterio-venous shunts by cinefluorography in the lungs of normal
      dogs.

PMID- 14949010
TI  - Absorption rates of colloid and milky suspensions of halogenated fats for
      hepatosplenography in the rat.

PMID- 14949011
TI  - Combination of hydrochloric acid and sodium hydroxide with human aortic
      albuminoid.

PMID- 14949012
TI  - Direct isolation of Histoplasma capsulatum from soil: probable etiological
      relationship to Camp Gruber pneumonitis.

PMID- 14949013
TI  - Effect of deficiencies of sodium and potassium on motility of the intestine of
      the rat.

PMID- 14949014
TI  - Vitamin B12 biosynthesis after oral and intravenous administration of inorganic
      Co60 to sheep.

PMID- 14949015
TI  - Viability of the Lansing strain of poliomyelitis virus in the bat (Eptesicus
      fuscus).

PMID- 14949016
TI  - Effects of isonicotinic acid derivatives on tubercle bacilli.

PMID- 14949017
TI  - Effect of age on Wallerian degeneration in the rat.

PMID- 14949018
TI  - Effect of estrogens on serum lipids and low density lipoproteins in men and
      women.

PMID- 14949019
TI  - Ineffectiveness of 688A (N-phenoxyisopropyl-N-benxyl-beta-chloroethylamine
      hydrochloride) in treatment of essential hypertension.

PMID- 14949020
TI  - Some observations on effect of gamma radiation on the biochemistry of the rat
      thymus.

PMID- 14949021
TI  - Cultivation of Endamoeba histolytica in embryonic fluids.

PMID- 14949022
TI  - Effect of heparin and treburon in postprandial hyperlipemia.

PMID- 14949023
TI  - Effect of multiple inoculations on interference between St. Louis encephalitis
      virus and equine encephalomyelitis virus.

PMID- 14949024
TI  - Abiological method for determining small quantities of sodium retaining
      substances.

PMID- 14949025
TI  - Production of pigments similar to those from hair from amino acid and keratin
      interaction.

PMID- 14949026
TI  - Hepatic catabolism of thyroid hormone studied by radioactive iodine in splenic
      autotransplants.

PMID- 14949027
TI  - Composition of urinary calculi from mink.

PMID- 14949028
TI  - Comparative measurements of temperature in liver, lung, and rectum of the rabbit.

PMID- 14949029
TI  - Effects of desoxycorticosterone and adrenocorticotrophic hormone on mercurial
      diuresis.

PMID- 14949030
TI  - Pyruvate metabolism and assessment of semen quality.

PMID- 14949031
TI  - Method for determination of vitamin A in stool.

PMID- 14949032
TI  - Protogen and its relation to ketoacids in metabolism of Tetrahymena.

PMID- 14949033
TI  - Effect of hyaluronidase on edema following experimental cold injury.

PMID- 14949034
TI  - Role of protogen in the oxidation of pyruvic acid.

PMID- 14949035
TI  - Effect of nitrogen mustard on virus of serum hepatitis in whole blood.

PMID- 14949036
TI  - Effect of hyaluronidase on reaction of rabbits to intradermal inoculations of
      vaccinia virus.

PMID- 14949037
TI  - Influence of body fat on duration of thiopental anesthesia.

PMID- 14949038
TI  - Casein and factor 3 in dietary necrotic liver degeneration; concentration of
      factor 3 from casein.

PMID- 14949039
TI  - Adenosine triphosphatase activity of the vascular system.

PMID- 14949040
TI  - Gastric secretion in Heidenhain pouches following section of vagus nerves to main
      stomach.

PMID- 14949041
TI  - Intrapleurally injected colloidal Au198 and growth and implantation of free tumor
      cells in pleural exudate.

PMID- 14949042
TI  - Pulmonary edema in oxygen poisoning.

PMID- 14949043
TI  - Uptake of radioactive sulfur by chondrosarcomas in man.

PMID- 14949044
TI  - Serum citric acid in Hodgkin's disease, lymphoma and carcinoma.

PMID- 14949045
TI  - Cortisone effect on pneumonitis produced in mice by exposure to a high oxygen
      atmosphere.

PMID- 14949046
TI  - Effects of ACTH, cortisone and adrenal cortical extract on carbohydrate
      metabolism of hypophysectomized dogs.

PMID- 14949047
TI  - Comparison of insulin hypersensitivity of adrenalectomized and of
      hypophysectomized dogs.

PMID- 14949048
TI  - Effects of C17-hydroxysteroids on urinary 17-ketosteroids in the rat.

PMID- 14949049
TI  - Separate identities of the Donath-Landsteiner hemolysin (PCH antibody) and
      treponemal immobilizing antibody.

PMID- 14949050
TI  - Inhibitory effect of antibiotics on virus of Rous sarcoma.

PMID- 14949051
TI  - Effects of prolonged high dosage with ascorbic acid.

PMID- 14949052
TI  - Alpha-Aminosulfonic acids and viral propagation.

PMID- 14949053
TI  - Antimalarial activities of triazine metabolites of chlorguanide and
      dichlorguanide.

PMID- 14949054
TI  - Occurrence of acute pulmonary edema in experimental alkalosis.

PMID- 14949055
TI  - Nature of an accelerator of prothrombin activation arising during storage of
      purified prothrombin.

PMID- 14949056
TI  - Effects of beta rays upon a single nerve fiber.

PMID- 14949057
TI  - A method of human plasmapheresis.

PMID- 14949058
TI  - Role of pituitary adrenal discharge in antipyretic action of hydroxyphenyl
      cinchoninic acid (HPCA).

PMID- 14949059
TI  - Adaptation of hypophysectomized rat to fasting.

PMID- 14949060
TI  - Spermicidal effect of certain physiologically active substances.

PMID- 14949061
TI  - Renotrophic-androgenic properties of orally administered androgens.

PMID- 14949062
TI  - Fetal x-irradiation and fertility.

PMID- 14949063
TI  - Lack of correlation between dietary level of manganese and growth rate of induced
      fibrosarcomas.

PMID- 14949064
TI  - Microscopy of synapses of non-excised frog heart.

PMID- 14949065
TI  - Growth of dogs on purified diet plus aureomycin and/or vit. B12.

PMID- 14949066
TI  - Complement-fixing murine typhus antibodies in vitamin deficiency states. III.
      Riboflavin and folic acid deficiencies.

PMID- 14949067
TI  - Effect of x-irradiation upon the enzyme systems of the mouse spleen.

PMID- 14949068
TI  - Studies on chick embryo adapted rabies virus. III. Duration of immunity in
      vaccinated dogs.

PMID- 14949069
TI  - Effects of aureomycin on renal lesions, liver lipid, and tissue choline in
      choline deficiency.

PMID- 14949070
TI  - Presence of complement in serum of the mouse.

PMID- 14949071
TI  - Humoral factors involved in the induction of liver regeneration in the rat.

PMID- 14949072
TI  - Pricking pain threshold in different body areas.

PMID- 14949073
TI  - Localizing properties of anti-rat-aorta antibodies.

PMID- 14949074
TI  - Antidiuretic effects of physostigmine and atropine in the dog.

PMID- 14949075
TI  - Nephrotoxic action of spermine.

PMID- 14949076
TI  - Studies on nicotinamide inhibitors.

PMID- 14949077
TI  - Changes in glucose tolerance as an index of improvement after electro-shock
      therapy.

PMID- 14949078
TI  - Significance of intermedin activity in adrenocorticotropic hormone preparation.

PMID- 14949079
TI  - Effect of various allergens and antibiotics on experimental poliomyelitis.

PMID- 14949080
TI  - Increased excretion of dehydroascorbic and diketogulonic acids by rats in the
      cold.

PMID- 14949081
TI  - Persistence of C14 anthranil-azo-ovalbumin in injected rabbits.

PMID- 14949082
TI  - II. Treatment to Flexner-Jobling carcinoma in Sprague-Dawley rats with 2,4,6
      triethylenimino-s-triazine (TEM).

PMID- 14949083
TI  - A critical examination of the histochemical staining technic for ascorbic acid.

PMID- 14949084
TI  - Antihistaminic action of pyronil.

PMID- 14949085
TI  - Some factors involved in the fibrogenesis of collagen in vitro.

PMID- 14949086
TI  - Reactions of the vessels of the rat kidney after experimental occlusion of the
      renal artery for various periods.

PMID- 14949087
TI  - Infra-red spectroscopy of brain tissue; a lipid fraction in normal and irradiated
      adult and fetal rats.

PMID- 14949088
TI  - Correction of anemia following hypophysectomy by administration of cobalt.

PMID- 14949089
TI  - A simple and sensitive histochemical method for calcium.

PMID- 14949090
TI  - Linkage studies of genes for sickling and MNS blood groups; negative findings.

PMID- 14949091
TI  - Effect of dihydroergotamine on epinephrine response in the hind-limb of dogs.

PMID- 14949092
TI  - Effect of dietary molybdenum upon chicks and poults.

PMID- 14949093
TI  - A method for quantitative identification of canine erythrocytes.

PMID- 14949094
TI  - Comparative effectiveness of five newly synthesized arsenical compounds in
      treatment of leukemia in mice.

PMID- 14949095
TI  - Chemotherapeutic activity of 6-sulfanilamido-2,4-dimethylpyrimidine (elkosin).

PMID- 14949096
TI  - Propagation of mumps virus in suckling mice and in mouse embryo tissue cultures.

PMID- 14949097
TI  - Occurrence of Coxsackie virus complement fixing antibodies in sera of normal
      monkeys.

PMID- 14949098
TI  - Effect of nitrogen mustard on nucleic acid metabolism.

PMID- 14949099
TI  - Effect of acetylcholine on St. Louis encephalitis infection in the mouse.

PMID- 14949100
TI  - Augmentation of rat ovarian weight induced by chorionic hormone.

PMID- 14949101
TI  - Effect of various plasma volume expanders on erythrocyte size.

PMID- 14949102
TI  - Effect of cobalt60 gamma radiation on susceptibility and immunity to trichinosis.

PMID- 14949103
TI  - Immunization of rabbits with type II pneumococcal polysaccharide.

PMID- 14949104
TI  - Development of resistance to 4-amino n10-methyl pteroylglutamic acid
      (Amethopterin) by Leuconostoc citrovorum.

PMID- 14949105
TI  - Comparison of antibacterial activity of single and combined sulfonamides.

PMID- 14949106
TI  - Studies on passive immunity in poliomyelitis. V. Lansing antibody levels in
      humans after gamma globulin administration.

PMID- 14949107
TI  - Role of externally produced hydrogen peroxide in damage to Paramecium aurelia by
      x-rays.

PMID- 14949108
TI  - Spectrophotometric studies on mixtures of purified diphtherial toxin and
      ferriprotoporphyrin IX.

PMID- 14949109
TI  - Effect of certain plant growth substances on oxidative phosphorylation in rat
      liver mitochondria.

PMID- 14949110
TI  - Placental transfer of radioactive digitoxin in rats and guinea pigs.

PMID- 14949111
TI  - Factors influencing development of hypophyseal tumors in mice after treatment
      with radioactive iodine.

PMID- 14949112
TI  - Blood-clotting studies on dogs internally irradiated with radio-gold.

PMID- 14949113
TI  - Rickettsialpox. II. Recovery of Rickettsia akari from mites Allodermanyssus
      sanguineus, from West Hartford, Conn.

PMID- 14949114
TI  - Effect of glucose on oxygen consumption and respiratory quotient of normal and
      denervated muscle.

PMID- 14949115
TI  - Microdetermination of carbon dioxide content of serum or plasma with glass
      electrode.

PMID- 14949116
TI  - Effect of parathyroids on radio-calcium uptake and exchange in rat tissues.

PMID- 14949117
TI  - Effect of sympathomimetic amines upon amino acid nitrogen content of the blood.

PMID- 14949118
TI  - Nucleic acid changes in sarcoma 180 following administration of aminopterin.

PMID- 14949119
TI  - A method for the biological preparation of deuterium-labeled cholesterol from the
      hen's egg.

PMID- 14949120
TI  - Smoking and asthma.

PMID- 14949121
TI  - Preliminary studies of a new anticoagulant drug.

PMID- 14949122
TI  - The effect of a surgically induced arteriovenous fistula on bone growth; report
      of case.

PMID- 14949123
TI  - Report of radium therapy for 1951.

PMID- 14949124
TI  - Investigation of a bacterial pyrogen as a therapeutic agent in neurologic
      disorders.

PMID- 14949125
TI  - [Significance of the common bull frog (Rana esculenta) for the detection and
      quantitative estimation of gonadotropic hormones in pregnant women].

PMID- 14949126
TI  - [Treatment of psychoneurosis by vagosympathetic infiltration].

PMID- 14949127
TI  - [Asthma and ACTH].

PMID- 14949128
TI  - [Charles Lenormant and Pierre Wilmoth at l'Hopital Cochin].

PMID- 14949129
TI  - [Morphological methods in hyperthyreosis].

PMID- 14949130
TI  - [A liver detoxification agent; mercaptopyruvic acid].

PMID- 14949131
TI  - [Practical organization of an aerosol therapy center in the hospital].

PMID- 14949132
TI  - [Medicine and revolution; Joseph Souberbielle].

PMID- 14949133
TI  - [Preliminary report on therapeutic value of nicotinic acid hydrazine in the
      treatment of tuberculosis].

PMID- 14949134
TI  - [Associated antibiotic and immunotherapy of brucellosis].

PMID- 14949135
TI  - [Blood cytochemistry; polysaccharides].

PMID- 14949136
TI  - [Unusual case of chronic inflammatory bronchial stenosis].

PMID- 14949137
TI  - [Physiological significance and clinical value of certain renal function tests].

PMID- 14949138
TI  - [Leukocytic constitutional changes].

PMID- 14949139
TI  - [Association of diabetes mellitus and leukemia; clinical aspects and review of
      the literature].

PMID- 14949140
TI  - [Carboxylases in the treatment of myasthenia gravis].

PMID- 14949141
TI  - [Considerations on three cases of pulmonary tumors].

PMID- 14949142
TI  - [Gastroenterology; birth and development of a new specialty].

PMID- 14949143
TI  - [Research on blood cytochemistry; polysaccharide reaction in cytodiagnosis of
      acute leukosis].

PMID- 14949144
TI  - [Bolen test in malignant neoplasms].

PMID- 14949145
TI  - [Case of leukemia with initial aplastic phase and with remission].

PMID- 14949146
TI  - [Mendel's and Hoogland's colorimetric method of determination of glycemia].

PMID- 14949147
TI  - [Diagnostic progress].

PMID- 14949148
TI  - [Histochemical study on eosinophil granulocytes in lymphogranulomatous tissue;
      proteins, glycides and lipids in cytoplasmic granules].

PMID- 14949149
TI  - [Primary recurrent echinococcosis of the gluteal muscles].

PMID- 14949150
TI  - [Quantitative determination of hemoglobin by peroxidase activity].

PMID- 14949151
TI  - [Use of synthetic preparation similar to vitamin B12 in the treatment of
      bronchial asthma].

PMID- 14949152
TI  - [Preliminary therapeutic experiences with isonicotinic acid hydrazide in
      pulmonary tuberculosis].

PMID- 14949153
TI  - [Experimental studies on variations induced by ACTH in asthma produced by
      histamine and acetylcholine].

PMID- 14949154
TI  - [Diffuse hemochromatosis with grave hepato-endocrino-cardiac syndrome;
      peculiarities of onset and course].

PMID- 14949155
TI  - [Cretin's operation and Filatov's tissue therapy in chronic arthropathies;
      preliminary note].

PMID- 14949156
TI  - [What is allergy?].

PMID- 14949157
TI  - [Chair of skin and syphilitic diseases].

PMID- 14949158
TI  - [Queyrat and Milian].

PMID- 14949159
TI  - [Annual report of antivenereal services in the Bouches-du-Rhone region].

PMID- 14949160
TI  - [Two years of systematic survey of syphilis in dyspensaries in Juvisy-sur-Orge].

PMID- 14949161
TI  - [Use of plexiglass slides for serologic flocculation reaction].

PMID- 14949162
TI  - [Commission on Venereal Diseases and Permanent Council of Social Hygiene].

PMID- 14949163
TI  - [The Nelson test. I. Results obtained at the Alfred-Fournier Institute during
      1951].

PMID- 14949164
TI  - [The Nelson test. II. Reflections of a clinician].

PMID- 14949165
TI  - [The Nelson test. III. Separation of the reagents and the treponemal
      immobilization factors in the serum by ultracentrifugation].

PMID- 14949166
TI  - [The Nelson test. IV. Effect of ultracentrifuging on the content of treponemal
      immobilization factors, antityphic agglutinins and anti-sheep hemolysins].

PMID- 14949167
TI  - [Social attitude of man in the light of I. P. Pavlov's objective physiology].

PMID- 14949168
TI  - [The Rendu-Osler disease].

PMID- 14949169
TI  - [Difficulties of diagnosis of tuberculosis in pneumoconiosis].

PMID- 14949170
TI  - [Determination of histamine in blood].

PMID- 14949171
TI  - [The descent of Hell].

PMID- 14949172
TI  - [Psychoanalytic sketch of the Aeneid].

PMID- 14949173
TI  - [Art and psychoanalysis].

PMID- 14949174
TI  - [Esthetic dissociation].

PMID- 14949175
TI  - [The death of the hero].

PMID- 14949176
TI  - [Reflections on projective tests].

PMID- 14949177
TI  - [Failure in the lives of men and nations].

PMID- 14949178
TI  - [Reflections on circumcision].

PMID- 14949179
TI  - [Responsibility in neurotic delinquency].

PMID- 14949180
TI  - [Symbolists and definitionists in graphology].

PMID- 14949181
TI  - [The psychology of values illustrated by a complete case history].

PMID- 14949182
TI  - [Jealousy in children].

PMID- 14949183
TI  - [Problem of aggressivity in boys; case history].

PMID- 14949184
TI  - [Father and son: clinical case report].

PMID- 14949185
TI  - [Familial neurosis and group neurosis].

PMID- 14949186
TI  - [Symbolists and definitionists in graphology].

PMID- 14949187
TI  - [Psychology of values illustrated by a complete case history].

PMID- 14949188
TI  - [The biological character of the Freudian psychoanalysis].

PMID- 14949190
TI  - [Psychosomatic problems in paraplegics].

PMID- 14949189
TI  - [Psychotherapy of children without interpretation of subconscious thoughts].

PMID- 14949191
TI  - [Vegetative neuroses post partum].

PMID- 14949192
TI  - [Encopretic children].

PMID- 14949193
TI  - [The lamapagode as psychological diagram].

PMID- 14949194
TI  - [Meeting of the German Neurologists and Psychiatrists in Stuttgart].

PMID- 14949195
TI  - [Anorexia, an equivalent of depression].

PMID- 14949196
TI  - [Recent progress in the analytic psychotherapy of psychoses].

PMID- 14949197
TI  - [Values and science].

PMID- 14949198
TI  - [Indications for psychotherapy of children].

PMID- 14949199
TI  - [Counter transference in psychoanalysis of children].

PMID- 14949201
TI  - [Case report of a day dreamer].

PMID- 14949200
TI  - [Healing of stutter by repetition of subsequent phases in child development by
      undergoing play therapy with the Sceno test].

PMID- 14949202
TI  - [The relation of psychoanalysis to the social theory].

PMID- 14949203
TI  - [Love and hate].

PMID- 14949204
TI  - [The Judas complex and thwarted escape into psychosis].

PMID- 14949205
TI  - [The indication for psychoanalysis].

PMID- 14949206
TI  - [Constitutional factors endangering personality development].

PMID- 14949207
TI  - [The problem of depression].

PMID- 14949208
TI  - [Experiments on psychodynamic problems].

PMID- 14949209
TI  - [Phenomenological aspect of affective contact].

PMID- 14949210
TI  - [Psychology & pedagogics of inner strength].

PMID- 14949211
TI  - [20 years of Eranos meetings in Moscia-Ascona (Switzerland)].

PMID- 14949212
TI  - Modifications of electric shock therapy.

PMID- 14949213
TI  - Ailurophobia and ornithophobia.

PMID- 14949214
TI  - Personality reintegration by lobotomy and psychotherapy; a case report.

PMID- 14949215
TI  - The neuroses of everyday living.

PMID- 14949216
TI  - Methods in graphologic diagnostics.

PMID- 14949217
TI  - Evaluation of treatment and related procedures in 1,216 cases referred to a
      mental hygiene clinic.

PMID- 14949218
TI  - Reaction to stress in schizophrenia.

PMID- 14949219
TI  - Acceptance in the therapeutic situation.

PMID- 14949220
TI  - Administration of the continued treatment service.

PMID- 14949221
TI  - The genesis of schizoid personality; a study of two cases developing
      schizophrenia.

PMID- 14949222
TI  - Psychotherapy of manic-depressive patients in the manic phase.

PMID- 14949223
TI  - Some notes on the psychotherapy of schizophrenia.

PMID- 14949224
TI  - Psychic disturbances in typhus fever.

PMID- 14949225
TI  - Prefrontal leukotomy; a clinical survey of 100 cases given an active retraining
      program in a mental hospital--addendum.

PMID- 14949226
TI  - LO, all our pomp of yesterday.

PMID- 14949227
TI  - [Sleep therapy].

PMID- 14949228
TI  - [The clinic of the protracted insulin coma].

PMID- 14949229
TI  - [Two different clinical pictures of the central nervous system caused by
      benzene].

PMID- 14949230
TI  - [Pathogenesis and therapy of neuresis nocturna].

PMID- 14949231
TI  - [Medical pedagogics of R.A. Pfeiffer].

PMID- 14949232
TI  - [Basic comments on medical psychology].

PMID- 14949233
TI  - [In memoriam Theodor Ziehen].

PMID- 14949234
TI  - [Polamidon therapy of extrapyramidal diseases].

PMID- 14949235
TI  - [Death after lumbal sympathetic block with psicain].

PMID- 14949236
TI  - [Observation of a schizophrenic patient before and after lobotomy].

PMID- 14949238
TI  - [Psychiatric aspects of hermaphroditism].

PMID- 14949237
TI  - [A schizophrenic patient treated with prefrontal leucotomy, tested by the
      Rorschach test; a case report].

PMID- 14949239
TI  - [Symptom changes and pathogenetic problems in O-tricresylphosphate poisoning].

PMID- 14949240
TI  - [On o-tricresylphosphate poisoning in tigers].

PMID- 14949241
TI  - [Work therapy at present time].

PMID- 14949242
TI  - [Clinic & pathology of the ganglia all forming neurinomata].

PMID- 14949243
TI  - [Provocation of psychosen in medical therapy & chronic alcoholism (psychoses due
      to antabuse)].

PMID- 14949244
TI  - [Forensic evaluation of psychoses caused by thallium].

PMID- 14949245
TI  - [Effects of castration].

PMID- 14949246
TI  - [Results of checking on the motometric scale of Osseretzky].

PMID- 14949247
TI  - [Criteria of advance].

PMID- 14949248
TI  - [The Kneipp therapy of vegetative dystonias].

PMID- 14949249
TI  - [Three cases of carbondisulfide poisoning of the nervous system with
      considerations of the exogenous types of reaction of Bonhoeffer].

PMID- 14949251
TI  - [Diagnosis & therapy of Langdon-Down's disease].

PMID- 14949250
TI  - [Epicrisis of 700 suicidal attempts].

PMID- 14949252
TI  - [Report from the 4th meeting of the Medical-Scientific Society for Psychiatry and
      Neurology of the University of Jena, at the University Psychiatric Clinic, Jena,
      October 14, 1951].

PMID- 14949253
TI  - [On the basis of Pavlov's theory].

PMID- 14949254
TI  - [Pavlov's theory of the second signal system, its basis and its position in
      Pavlov's whole works].

PMID- 14949255
TI  - [Posttraumatic dyslexia and dysgraphia in a 6 3/4 years old child].

PMID- 14949256
TI  - [Evaluation of testamentary capacity of deceased in actions for invalidation].

PMID- 14949257
TI  - [Excessive body seize of an 11 years old child].

PMID- 14949258
TI  - [The active mimic psychomotoric of Kwint according to the age; a critical
      investigation of normal children and of children with brain damage].

PMID- 14949259
TI  - [Physiology of thinking process].

PMID- 14949260
TI  - [Therapy of multiple sclerosis in women by x-ray castration].

PMID- 14949261
TI  - Phobic symptoms and dream interpretation.

PMID- 14949262
TI  - The genesis of antisocial acting out in children and adults.

PMID- 14949263
TI  - Features from a case of homosexuality.

PMID- 14949265
TI  - The fantasies of W.S. Gilbert.

PMID- 14949264
TI  - The feast of tantalus.

PMID- 14949266
TI  - Repression and the electroencephalogram.

PMID- 14949267
TI  - Psychosomatic problems; methodology, research material and concepts.

PMID- 14949268
TI  - Structural aspects of psychotherapy.

PMID- 14949269
TI  - The thematic apperception test of a schizophrenic interpreted according to new
      rules.

PMID- 14949270
TI  - Fantasies concerning convulsive therapy.

PMID- 14949272
TI  - The neurophysiology of learning and delayed reward learning.

PMID- 14949271
TI  - Innate constituents of complex responses in primates.

PMID- 14949273
TI  - Delayed reward learning.

PMID- 14949274
TI  - Maier's behavior theory.

PMID- 14949275
TI  - An orientation for research on thinking.

PMID- 14949276
TI  - Incidental memory and problem-solving.

PMID- 14949277
TI  - Effect, change, and expectation of reward.

PMID- 14949278
TI  - Some criticisms of a mathematical model for simple learning.

PMID- 14949279
TI  - Approach and avoidance; a reply.

PMID- 14949280
TI  - Gilinsky's theory of visual size and distance.

PMID- 14949281
TI  - Gilinsky's equations for perceived size and distance.

PMID- 14949282
TI  - The bibsonian visual field.

PMID- 14949283
TI  - The role of hedonic processes in the organization of behavior.

PMID- 14949284
TI  - Dynamic systems and theory construction.

PMID- 14949285
TI  - "What is learned?"--A theoretical blind alley.

PMID- 14949286
TI  - A unifying theoretical approach to motor learning.

PMID- 14949287
TI  - Objectivity in systematic and "idiodynamic" psychology.

PMID- 14949288
TI  - The formation of negative habits: A neurophysiological view.

PMID- 14949289
TI  - Three estimates of differential excitatory tendency.

PMID- 14949290
TI  - Perceptual defense.

PMID- 14949291
TI  - A note on one-tailed and two-tailed tests.

PMID- 14949292
TI  - Some remarks on the Ames oscillatory effect.

PMID- 14949293
TI  - Toward a general theory of perception.

PMID- 14949294
TI  - The investigation of repression as an instance of experimental idiodynamics.

PMID- 14949295
TI  - Relationship of specific attitudes and emotions to certain bodily diseases.

PMID- 14949296
TI  - Psychometric investigation of the relationship between emotional repression and
      the occurrence of psychosomatic symptoms.

PMID- 14949297
TI  - Psychosomatic phenomena in animals.

PMID- 14949298
TI  - A program of teaching a psychodynamic orientation to resident physicians in
      medicine.

PMID- 14949299
TI  - Effects of SKF# 501 (N-9-fluorenyl N,N-ethyl-beta-chloroethylamine) on
      cardiovascular manifestations of hypoglycemia following administration of
      insulin.

PMID- 14949300
TI  - Some psychodynamic considerations of psychosomatic skin disorders;
      plethysmographic and psychoanalytic observations.

PMID- 14949301
TI  - Dermatitis: an hysterical conversion symptom in a young woman; psychosomatic
      conference.

PMID- 14949302
TI  - Psychological reactions to cortisone; a clinical note.

PMID- 14949303
TI  - A note on the significance of fatigue.

PMID- 14949304
TI  - [Effect of heart diseases on menstruation].

PMID- 14949305
TI  - [Case of ovarian pregnancy].

PMID- 14949306
TI  - [Functional changes of the adrenal cortex in pre-eclampsic states and in
      eclampsia].

PMID- 14949307
TI  - [Diagnosis of pregnancy with biologic and chemical tests; Galli-Mainini and
      Carson-Saeks tests].

PMID- 14949308
TI  - [Genital malformations with special reference to didelphic uterus and vaginal
      atresia].

PMID- 14949309
TI  - [Ophthalmoscopic findings in pregnancy toxemias].

PMID- 14949310
TI  - [Studies on protein deficiency in pregnancy; studies on tryptophan content of
      blood proteins].

PMID- 14949311
TI  - [Clinical considerations on ectopic pregnancy].

PMID- 14949312
TI  - [Obstructed lactation and progesterone].

PMID- 14949313
TI  - [Histochemical studies on alkaline phosphatases in the human vagina in relation
      to sexual hormones].

PMID- 14949314
TI  - [Radioisotopes in gynecology and obstetrics].

PMID- 14949315
TI  - [Considerations on a case of associated late lesions following radiotherapy of
      cancer of the cervix uteri].

PMID- 14949316
TI  - [Blood phosphatases, acids, and alkali in uterine and vaginal neoplasms following
      radiotherapy and surgery].

PMID- 14949317
TI  - The location of cholinesterase in the central nervous system.

PMID- 14949318
TI  - Reversible effects of anticoagulants and protamine on alimentary lipaemia.

PMID- 14949319
TI  - The oxidation of oxyhaemoglobins from different animal species.

PMID- 14949320
TI  - The diffusion of atmospheric gases through fats and oils.

PMID- 14949321
TI  - Studies of the circulation in haemorrhagic shock by means of erythrocytes
      labelled with radio-phosphorus.

PMID- 14949323
TI  - Investigations of an allergic factor in alcohol addiction.

PMID- 14949322
TI  - The blood alcohol curve in zonal necrosis of the liver.

PMID- 14949324
TI  - Prevalence of alcoholism in the population and among suicides and accidents from
      poisoning, Massachusetts 1938-1948.

PMID- 14949325
TI  - The estimate of the number of alcoholics in the U.S.A. for 1949 in the light of
      the sixth revision of the international lists of causes of death.

PMID- 14949326
TI  - Drinking behavior in the State of Washington.

PMID- 14949328
TI  - Community surveys: their aims and techniques, with special reference to problems
      of alcoholism.

PMID- 14949327
TI  - A two-year survey of alcoholic patients in a California state hospital.

PMID- 14949329
TI  - An experience of a nonalcoholic in Alcoholics Anonymous leadership.

PMID- 14949330
TI  - Soil genesis and the pedogenic factors.

PMID- 14949331
TI  - The influence of the nerve in regeneration of the amphibian extremity.

PMID- 14949332
TI  - The ideal x-ray technician.

PMID- 14949333
TI  - A supplementary view for demonstrating salivary calculi.

PMID- 14949334
TI  - The General Council of the Whitley Councils for the health services (Gt. Brit.).

PMID- 14949335
TI  - Design and organization of the Radiographic darkroom.

PMID- 14949336
TI  - The induction coil and the water ram.

PMID- 14949337
TI  - The mattheichristiansen manoeuvre in the excretory urography of children.

PMID- 14949338
TI  - Radiography of the hip joint and upper end of the femur.

PMID- 14949339
TI  - Radiography of mentally defective children.

PMID- 14949340
TI  - [A new technique in x-ray diagnosis; retropneumoperitoneum].

PMID- 14949341
TI  - [Cholangiography and its clinical interpretation].

PMID- 14949342
TI  - [Plateau pits in the stomach].

PMID- 14949343
TI  - [Statistical results of 313 cases of cancer of the larynx treated with
      roentgenotherapy from 1928 to 1946 in the National Cancer Institute in Milano].

PMID- 14949344
TI  - [Pneumoperitoneum in the radiological diagnosis of tumors of the fundus
      ventriculi].

PMID- 14949345
TI  - [Selective radiological appearance of the interureteral crest and the terminal
      tract of the ureters].

PMID- 14949346
TI  - [Stratigraphy of calculi of the bladder].

PMID- 14949347
TI  - [Fibrolymphangioma of the diaphragm].

PMID- 14949348
TI  - [Experimental identification of an important anatomical site on the cranium].

PMID- 14949349
TI  - [A case of gastric phytobezoar].

PMID- 14949350
TI  - [Weight and histological changes in the thymus and spleen in female
      adrenalectomized and irradiated rats].

PMID- 14949351
TI  - [Radiological syndrome of spontaneous pneumoperitoneum].

PMID- 14949352
TI  - [Post-operative cholangiography and the pancreatic duct; clinico-radiological
      findings and personal observations on several cases].

PMID- 14949353
TI  - [Grid radiography as a diagnostic aid].

PMID- 14949354
TI  - [New safety circuit for therapeutic apparatus].

PMID- 14949355
TI  - [Gutmann radioclinical technic in the early diagnosis of gastric cancer].

PMID- 14949356
TI  - [Difficulties in the radiological interpretation of tumor shadows at the right
      base of the chest].

PMID- 14949357
TI  - [Peculiar radiotransparencies of bones and their anatomohistological
      significance].

PMID- 14949358
TI  - [Use of high frequencies, continuous constant or pulsating (100-180 kV) and of
      low anode currents (2-8 mA) in schermography].

PMID- 14949359
TI  - [Kidney neoplasms and urography].

PMID- 14949360
TI  - [Anatomo-pathological comment on the radiological picture of renal tumors; 39
      cases].

PMID- 14949361
TI  - [Therapy of parotid tumors; 35 cases].

PMID- 14949362
TI  - [First tests in hepatolienography with ethyl diiodostearate (angiopac)].

PMID- 14949363
TI  - [Angiopac phlebography].

PMID- 14949364
TI  - [13 Cases of sarcoma of the uterus].

PMID- 14949365
TI  - [Aneurysm in coarctation of the aorta].

PMID- 14949366
TI  - [Experimental research on the existence of an anti-carcinogenic action of the
      blood of cancerous subjects treated with radiotherapy].

PMID- 14949367
TI  - [Atypical thoracic malformation mistaken on the x-ray for pulmonary lesions].

PMID- 14949368
TI  - [Reticuloendothelioma and reticulosarcoma].

PMID- 14949369
TI  - [Malignant polyostotic reticuloma].

PMID- 14949370
TI  - [Radiography of tympano-jugular glomus tumors].

PMID- 14949371
TI  - [Case of plasmocytoma simulating osteomalacia].

PMID- 14949372
TI  - [Experimental study of the primary radiological manifestations of osteoporosis].

PMID- 14949373
TI  - [Alterations of the lumbar vertebrae in a rare case of primary iliac aneurysm].

PMID- 14949374
TI  - [Two cases of fissure of the anterior arch of the atlas].

PMID- 14949375
TI  - [Looser's Umbauzonen with atypical multiple localizations].

PMID- 14949376
TI  - [Arthrosis of the coronal suture in cranioses].

PMID- 14949377
TI  - [Radiological study of articular and periarticular soft parts; normal and post
      traumatic radiography of the soft parts of the tibiotarsal joint].

PMID- 14949378
TI  - [Case of lipoma of the corpus callosum; radiographic study].

PMID- 14949379
TI  - [Necessity of perfecting contrast media in the radiological examination of the
      digestive apparatus].

PMID- 14949380
TI  - [Hypertransparent renal calculosis].

PMID- 14949381
TI  - [Comparative results of intracavitary aqueous and oily contrast media during
      Monaldi's drainage].

PMID- 14949382
TI  - [Radiological picture of intraventricular epidermoid].

PMID- 14949383
TI  - [Quantity of energy absorbed by the organism in radiodiagnosis].

PMID- 14949384
TI  - [Radiological study of plasma-tissue circulation].

PMID- 14949385
TI  - [Arteriography of the extremities, abdominal aorta and its branches].

PMID- 14949387
TI  - [Genesis of cancer of the uterus].

PMID- 14949386
TI  - [Radiological contribution to the study of the dynamic circulation of the legs].

PMID- 14949388
TI  - [Cure of cancer of uterine cervix in the first stage].

PMID- 14949389
TI  - [Radiotherapy of cancer of the uterine cervix in second, third and fourth
      stages].

PMID- 14949390
TI  - [Ultrasonics in biology and therapy].

PMID- 14949391
TI  - [Direct radiological demonstration of the pancreas].

PMID- 14949392
TI  - [Radiological diagnosis of reno-ureteral colic].

PMID- 14949393
TI  - [Contribution to the radiological study of the soft parts of the knee].

PMID- 14949394
TI  - [Kymography in pleuropericardial adhesions; modifications of graphs during
      respiratory phases].

PMID- 14949395
TI  - [Case of thrombosis of the common carotid artery; neuroradiological
      considerations].

PMID- 14949396
TI  - [Clinical and statistical report on carcinoma of the mouth and pharynx treated
      from 1928-1945. VIII. Results of radiotherapy in carcinoma of the hard palate (38
      cases)].

PMID- 14949397
TI  - Roentgen therapy in vitreous hemorrhage and hemorrhagic glaucoma.

PMID- 14949398
TI  - Extraperitoneal pneumography.

PMID- 14949399
TI  - Some obscure factors in the production of unusual small bowel patterns.

PMID- 14949400
TI  - Acute fulminating idiopathic ulcerative colitis; report of a case showing unusual
      roentgenologic and clinical features.

PMID- 14949401
TI  - Massive fatal embolism during barium enema study.

PMID- 14949402
TI  - Syphilis of the stomach.

PMID- 14949403
TI  - A new technic in the study of the mucosal pattern in the cardiac area of the
      stomach.

PMID- 14949404
TI  - Aberrant pancreatic tissue in the gastric antrum; report of seven cases.

PMID- 14949405
TI  - Hereditary multiple exostoses.

PMID- 14949406
TI  - Paradoxical expiratory ballooning of the hypopharynx in siblings with bilateral
      choanal atresia.

PMID- 14949407
TI  - Hodgkin's disease; a statistical report.

PMID- 14949408
TI  - Roentgen therapy in some non-malignant conditions.

PMID- 14949409
TI  - Segmental localization of pulmonary disease on the postero-anterior chest
      roentgenogram.

PMID- 14949410
TI  - Roentgen doses during diagnostic procedures.

PMID- 14949411
TI  - Segmental anatomy of the lung.

PMID- 14949412
TI  - [Syphilis and genius].

PMID- 14949413
TI  - [Effect of folliculo-stimulating pituitary hormone and human chorionic
      gonadotrophin on the metabolism of progesterone].

PMID- 14949414
TI  - [Comparative research on growth factors of various origins].

PMID- 14949415
TI  - [Hydrosoluble substances in egg yolk and in Serono bioplastin: free amino acids].

PMID- 14949416
TI  - [Artificial radioactivity its applications in biology and medicine].

PMID- 14949417
TI  - [Syphilis and genius. II..].

PMID- 14949418
TI  - [Pathogenesis of mercurial polyuria].

PMID- 14949419
TI  - [Gastro-duodenal ulcer and its medico-legal aspects].

PMID- 14949420
TI  - [Certain consideration on the importance of illumination and selection of colors
      in industry].

PMID- 14949421
TI  - [Thyroid function tests in endemic cretinism].

PMID- 14949422
TI  - [Traumatic intracranial pneumatocele and hydropneumatocele].

PMID- 14949423
TI  - [Local cortisone therapy in ophthalmology].

PMID- 14949424
TI  - [Role of hemostasis (possibly greater than of antisepsis) in the development of
      abdominal surgery].

PMID- 14949425
TI  - [Psychoneuroses evaluated with simplified and clarified criteria].

PMID- 14949426
TI  - [Articulation of the tarsus of the human foot in adduction and in abduction of
      the human foot].

PMID- 14949427
TI  - [Euthanasia].

PMID- 14949428
TI  - [Recent pathogenic concepts of favism in its various aspects].

PMID- 14949429
TI  - [Method psychiatric expert testimony].

PMID- 14949430
TI  - [Chronic subdural hematomas].

PMID- 14949431
TI  - [Myocardial infarction].

PMID- 14949432
TI  - [Precocious skeletal development in hypersomic and adipose adolescents;
      radiological study on 33 cases].

PMID- 14949433
TI  - [Tuberculosis and the adrenal cortex; urinary 17-ketosteroids and 11-oxysteroids
      during collapse therapy of pulmonary tuberculosis].

PMID- 14949434
TI  - [Excitometabolic effect of endovenous amino acids mixtures: normal diagram].

PMID- 14949435
TI  - [Excitometabolic effect of endovenous amino acids mixtures: diagram in arterial
      hypertension and in circulatory decompensation].

PMID- 14949436
TI  - [Excitometabolic of certain intravenous amino acids in Basedow's disease].

PMID- 14949437
TI  - [Circulatory anticoagulants in physiological conditions, in thrombophlebitic
      diseases and in thrombogenic diathesis, in liver diseases, in hemorrhagic
      diseases (hemophilia, Werlhof's disease, hemorrhagic syndromes due to circulatory
      anticoagulants) in blood diseases, action of dicumarol and of heparin on
      circulatory anticoagulants].

PMID- 14949438
TI  - [Problem of recuperation in pulmonary tuberculosis].

PMID- 14949439
TI  - [Anatomico-clinical statistical study of valvular modifications of the heart].

PMID- 14949440
TI  - [Prophylaxis and therapy of asymmetrical defects in school children].

PMID- 14949441
TI  - [Traumatic apophyseal osteochondrolysis of the pelvis in young football players].

PMID- 14949442
TI  - [Terramycin].

PMID- 14949443
TI  - [Pathogenetic problem of cancer].

PMID- 14949444
TI  - [Value of electrocardiographic examination in hypertensive patients].

PMID- 14949445
TI  - [Considerations on an amino acid and arsenical preparation (trophistine) in
      tuberculosis].

PMID- 14949446
TI  - [Epidemic hepatitis; development of old catarrhal jaundice into modern concept of
      viral hepatitis].

PMID- 14949447
TI  - [Surgical treatment of osteoarticular tuberculosis of evolutive phase treated
      with antibiotics].

PMID- 14949448
TI  - [Photogenic epilepsy; a new nosologic entity].

PMID- 14949449
TI  - [Phagocytic effect of tyrothricin in vitro].

PMID- 14949450
TI  - [Use of intravenous novocaine in the treatment of postoperative urinary
      retention].

PMID- 14949451
TI  - [Cutaneous tuberculosis; therapy].

PMID- 14949452
TI  - [Observations on the use of khellin in coronary insufficiency].

PMID- 14949454
TI  - [Present state of the problem of acute renal insufficiency].

PMID- 14949453
TI  - [Quick test (prothrombin time) in surgery].

PMID- 14949455
TI  - [Clinical aspects of the effect of meteorological factors in arterial
      hypertension].

PMID- 14949456
TI  - [Allergic dermatoses].

PMID- 14949457
TI  - [Cardiological consultation; rheumatism and the heart].

PMID- 14949458
TI  - [Considerations on immediate and remote results of 100 operated cases of varicose
      veins of the lower extremities].

PMID- 14949459
TI  - [Spreading of venereal diseases in Naples].

PMID- 14949460
TI  - [Simple apparatus applied with pipette for blood count].

PMID- 14949461
TI  - [Leonardo da Vinci as a morphologist].

PMID- 14949462
TI  - [Certain considerations on heparin therapy].

PMID- 14949463
TI  - [Phenylpyruvic oligophrenia].

PMID- 14949464
TI  - [Certain considerations on modern concepts of the treatment of typhus
      abdominalis].

PMID- 14949465
TI  - [Medico-legal aspects of food poisoning].

PMID- 14949466
TI  - [Therapy of anemic-depressive states following acute exhaustive diseases].

PMID- 14949467
TI  - [Study on heterotrophic thyroid diseases].

PMID- 14949468
TI  - [Phlyctenular or scrofulus keratoconjunctivitis; proposals for antibiotic
      therapy; preliminary note and considerations].

PMID- 14949469
TI  - [Research on the hypoglycemic action of PAS].

PMID- 14949470
TI  - [Epicranial vein for transfusion in pediatric practice].

PMID- 14949471
TI  - [Three cases of stammering treated with diethyl ammonium p-aminobenzoate].

PMID- 14949472
TI  - [Liver protective therapy in acquired neurasthenic syndrome].

PMID- 14949473
TI  - [Synthomycetin therapy of carbuncles].

PMID- 14949474
TI  - [Ictero-hemoglobinuric favism as immunological hemolytic anemia; serological
      findings on atypical antibodies].

PMID- 14949475
TI  - [Behavior of the Benda granulogram in leprosy].

PMID- 14949476
TI  - [Interpretation of the thin capillary line on the middle of the right lung].

PMID- 14949477
TI  - [PAS therapy of empyema caused by artificial pneumothorax].

PMID- 14949478
TI  - [Adequate blood supply for the foot by a single branch of the tibioperoneal
      trunk].

PMID- 14949479
TI  - [Anatomo-radiological interpretation of the capillary line].

PMID- 14949480
TI  - [Effect of antibiotics (penicillin and streptomycin) on the lysozyme property of
      the blood].

PMID- 14949481
TI  - [Effect of streptomycin on the tuberculin skin reaction].

PMID- 14949482
TI  - [Passive transmission of sensitivity to light].

PMID- 14949483
TI  - [Effect of the blood of cancer patients on the precipitation of colloidal dye
      binding by opposite electric charges].

PMID- 14949484
TI  - [Behavior of blood lysozyme in blood and in blister fluid of patients with
      pyoderma].

PMID- 14949485
TI  - [Phytotoxic property of blood, urine and blister fluid of leprous subjects].

PMID- 14949486
TI  - [Streptomycin therapy of leprosy].

PMID- 14949487
TI  - [Special technics of rotation x-ray therapy].

PMID- 14949488
TI  - [Retropneumoperitoneum and posterior pneumomediastinum].

PMID- 14949489
TI  - [3 years of electronarcosis; clinico-therapeutic contribution and results].

PMID- 14949490
TI  - [The skipped administrative elections (10 June 1951) of mental patients committed
      to the Teramo Psychiatric Hospital].

PMID- 14949491
TI  - [The Wassermann reaction with Treponema antigen in 100 neuropsychiatric
      patients].

PMID- 14949492
TI  - [Italian Association of Psychiatric Hospital Physicians; report on the
      regulations to new laws].

PMID- 14949493
TI  - [Report on the problem of physicians' pensions].

PMID- 14949494
TI  - [Civil service status of physicians of psychiatric hospitals].

PMID- 14949495
TI  - [A complex case of hypogenitalism].

PMID- 14949496
TI  - [Factors determining color and form aptitude; observations conducted with the
      bunch of grapes test and the ring test with the feeble-minded and epileptic].

PMID- 14949497
TI  - [Results and critical considerations of the application of the tsedek test for
      schizophrenics and relatives].

PMID- 14949498
TI  - [Bilateral deafness test in mental diseases].

PMID- 14949499
TI  - [The Thorn test and shock therapy].

PMID- 14949500
TI  - [Tuberculosis and mental diseases; clinico-statistical review of the Tuberculosis
      ward of the Provincial Psychiatric Hospital of Novara 1946-51].

PMID- 14949501
TI  - [The prognosis of cerebral vascular lesions].

PMID- 14949502
TI  - [A case of Dupuytren's disease treated with vitamin E].

PMID- 14949503
TI  - [Tonicity of the neurovegetative system (Rizzo method) in epileptic syndromes].

PMID- 14949504
TI  - [Bergamo Neuropsychiatric Hospital in the dacade from 1941 to 1950].

PMID- 14949505
TI  - [Psychoanalysis, psychotherapy and their professional practice].

PMID- 14949506
TI  - [The Freudian unconscious: thought, sleep, dreams].

PMID- 14949507
TI  - [Diagnosis of peptic ulcer].

PMID- 14949508
TI  - [Localization of mental functions in the brain].

PMID- 14949509
TI  - [Barbiturate poisoning; clinical manifestations].

PMID- 14949510
TI  - [Biological banks].

PMID- 14949511
TI  - [Third Argentina Congress on Tuberculosis, Rosario, 29-31 October 1951].

PMID- 14949512
TI  - [Nosography of ankylosing spondylitis].

PMID- 14949513
TI  - [Buccal goniometer; apparatus for measurement functional capacity of the temporo
      mandibular joint in rheumatoid arthritis].

PMID- 14949514
TI  - [Critical considerations on more common radiological technics used in vertebral
      arthropathies].

PMID- 14949515
TI  - [Initial case of hypertrophic pulmonary osteoarthropathy].

PMID- 14949516
TI  - [Clinico-biological observations in cortisone and ACTH therapy].

PMID- 14949517
TI  - [Study on the relationship between chorea minor and rheumatic infection; anti
      streptolytic titer].

PMID- 14949518
TI  - [Modifications of erythrosedimentation rate and of fibronogemia in rheumatism
      treated with salicylates and with cortisone].

PMID- 14949519
TI  - Surgical lesions of the esophagus, including discussions of esophagitis,
      "spontaneous" (acid-peptic) perforation of the esophagus, dystonia (cardiospasm)
      paraesophageal hernia, varices and cancer, together with remarks upon surgical
      management of peptic ulcer.

PMID- 14949520
TI  - Spontaneous rupture of the esophagus.

PMID- 14949521
TI  - Histochemistry of the gastrointestinal tract.

PMID- 14949522
TI  - Proctologic principles.

PMID- 14949523
TI  - Treatment of gastrointestinal complications with resion, a multiple adsorbent, in
      chronic alcoholic patients.

PMID- 14949524
TI  - Megacolon, volvulus of sigmoid, and hepatodiaphragmatic interposition of colon
      (Chilaiditi's symptom).

PMID- 14949525
TI  - The bile in pregnancy.

PMID- 14949527
TI  - [Sequels postcolecistectomia].

PMID- 14949526
TI  - [Hospital residencies].

PMID- 14949528
TI  - [Modern concept of male genital tuberculosis].

PMID- 14949529
TI  - [Gynandroid hermaphroditism; identification of the sex and reconstitution of the
      external genitalia].

PMID- 14949530
TI  - [Evaluation of the transversalis fascia in inguinal hernioplasty; original
      interpretation].

PMID- 14949531
TI  - [Tuberculous anorectal fistulas].

PMID- 14949532
TI  - [Professor Baptista Pereira Durval].

PMID- 14949533
TI  - [The teeth and focal infection].

PMID- 14949534
TI  - [Silver, ammonia and hydrogen peroxide in root canal therapy].

PMID- 14949535
TI  - [Histophysiology of the gingival sulcus].

PMID- 14949536
TI  - [Arsenical encephalopathy; clinical case cured with BAL, similar case without
      treatment with fatal outcome].

PMID- 14949537
TI  - [Osteochondrodystrophy deformans (Morquio's disease)].

PMID- 14949538
TI  - [Rh sensitivity as a cause of fetal erythroblastosis and hemolytic anemia in a
      child].

PMID- 14949539
TI  - [Studies on pyloric stenosis].

PMID- 14949540
TI  - [Tuberculous meningitis treated with streptomycin; review of 107 cases at the
      Hospital Luis Calvo Mackenna].

PMID- 14949541
TI  - [Angiocardiography in child].

PMID- 14949542
TI  - [Occupation arsenical poisoning].

PMID- 14949543
TI  - [Experimental serum nephritis].

PMID- 14949544
TI  - [Agglutination of sheep erythrocytes sensitized by blood serum of rheumatoid
      arthritis patients].

PMID- 14949545
TI  - [Nitrogen mustard therapy of uveitis of unknown etiology].

PMID- 14949546
TI  - [Our experience in the treatment of psoriasis].

PMID- 14949547
TI  - [New simplified technic for one stage cystoprostatovesiculectomy].

PMID- 14949548
TI  - [Schizophrenic complexes].

PMID- 14949549
TI  - [Eclamptic crises in arterial hypertension].

PMID- 14949550
TI  - [Reinfection in eruptive pluriorificial fever].

PMID- 14949551
TI  - [Case of spontaneous hematoma of the cerebellum].

PMID- 14949552
TI  - [Treatment of auricular fibrillation].

PMID- 14949553
TI  - [Etiopathogenesis of gastroduodenal ulcer].

PMID- 14949554
TI  - [Neutralization of the biochemical consequences of nephrectomy by different types
      of kidney extracts].

PMID- 14949555
TI  - [Mechanism of the nutritive repercussion of enteritis; nutritive value of feces
      in health and disease].

PMID- 14949556
TI  - [Exudative pericarditis and its treatment].

PMID- 14949557
TI  - [Contribution to the study of blood in liver cirrhosis].

PMID- 14949558
TI  - [Antibiotic therapy of pneumococcal meningitis].

PMID- 14949560
TI  - [Chesterman syndrome; case reports].

PMID- 14949561
TI  - [Case of chronic ascending pyelonephritis].

PMID- 14949562
TI  - [New syndrome: chronic rheumatoid syndrome due to occult brucellosis].

PMID- 14949563
TI  - [Enzyme therapy with streptokinasestreptodornase].

PMID- 14949564
TI  - [Mycotic leptomeningitis; torulosis of the nervous system].

PMID- 14949565
TI  - [Cirrhosis and cancer of the liver].

PMID- 14949566
TI  - [Thromboangiitis obliterans; sympathectomy].

PMID- 14949567
TI  - [Lithasic obstructive jaundice].

PMID- 14949568
TI  - [Renal adenoma in pulmonary tuberculosis].

PMID- 14949569
TI  - [Brain in normal and pathological old age].

PMID- 14949570
TI  - [Arterial origin of hypertensive substance].

PMID- 14949571
TI  - [Endocrine cystic mastitis and cancer of the breast].

PMID- 14949572
TI  - [Topographical value of cerebellar clinical symptoms].

PMID- 14949573
TI  - [Graphic presentation of the somatic morphotype constitution].

PMID- 14949574
TI  - [Acute perforations of the stomach, duodenum and jejunum].

PMID- 14949575
TI  - [Possibility of organic vascular complications during crises of inveterate
      migraine].

PMID- 14949576
TI  - [Marcus Gunn phenomenon].

PMID- 14949577
TI  - [Osseous dysnucleoplasia].

PMID- 14949578
TI  - [Treatment of acute open perforations of the stomach and duodenum].

PMID- 14949579
TI  - [Laennec's hepatic cirrhosis].

PMID- 14949581
TI  - [Regional ileitis].

PMID- 14949580
TI  - [Villous tumor of the rectum].

PMID- 14949582
TI  - [Five cases of subcortical cerebral hemorrhage].

PMID- 14949583
TI  - [Cancer of the transverse colon].

PMID- 14949584
TI  - [Recklinghausen's disease, associated with gigantism and gastric ulcer].

PMID- 14949585
TI  - [Hypophysial infantilism].

PMID- 14949586
TI  - [Concept of reinfection in tuberculosis].

PMID- 14949587
TI  - [Diarrhea and steatorrhea; contribution to the knowledge of sprue and
      repercussion type enteritis].

PMID- 14949588
TI  - [Results of chloramphenicol therapy in fifteen cases of typhoid fever].

PMID- 14949589
TI  - [Classification of esplenomegalias splenomegaly].

PMID- 14949590
TI  - [Study on the possibility of predicting cerebral hemorrhage in arterial
      hypertension].

PMID- 14949592
TI  - [Subtotal sacrococcygeal agenesis].

PMID- 14949591
TI  - [Confusion in anuria].

PMID- 14949593
TI  - [Dosage of vitamin D; case of rickets].

PMID- 14949594
TI  - [Clinical aspects and treatment of acute barbiturate poisoning].

PMID- 14949595
TI  - [Gynecomastia].

PMID- 14949596
TI  - [Pathological anatomy of amyotrophic lateral sclerosis].

PMID- 14949597
TI  - [Psychic factors in the etiopathogenesis of asthma].

PMID- 14949598
TI  - [Normal and pathological piezogram; conclusions on 400 cases].

PMID- 14949599
TI  - [Problem in the diagnosis of chronic appendicitis].

PMID- 14949600
TI  - [Hypersplenia].

PMID- 14949601
TI  - [Sudden blindness due to acute edema of the optic nerve].

PMID- 14949602
TI  - [Regional ileitis (Crohn's disease)].

PMID- 14949603
TI  - [Transition from the pyloroduodenal syndrome to ulcer].

PMID- 14949604
TI  - [Surgical treatment of cancer of the colon].

PMID- 14949605
TI  - [Pulmonary tumor with osseous metastasis].

PMID- 14949606
TI  - [Interstitial nephritis with evolution to sclerosis].

PMID- 14949607
TI  - [Calcified mitral lesion].

PMID- 14949608
TI  - [Squamous cell bronchial cancer].

PMID- 14949610
TI  - [Clinical and nosological problem of the so-called mesenterium commune].

PMID- 14949609
TI  - [Heart in anthracosilicosis].

PMID- 14949611
TI  - [Diverticulosis of the colon and its complications].

PMID- 14949612
TI  - [How to tell, in a man with slight hypertension, whether or not he is likely to
      have a vascular accident].

PMID- 14949613
TI  - [Radiological diagnosis of cancer of the stomach].

PMID- 14949614
TI  - [Study of the bronchosegmentary anatomy of the upper left lobe and its variations
      in 50 cases].

PMID- 14949615
TI  - [Carcinotoxic cerebellar atrophy; anatomico-clinical observation].

PMID- 14949616
TI  - [Accessory or aberrant pancreas].

PMID- 14949617
TI  - [Case of velopalatine myoclonia associated with subdural hematoma following
      cranial traumatism].

PMID- 14949618
TI  - [Medical treatment of arterial hypertension].

PMID- 14949619
TI  - [Post-cholecystectomy syndromes].

PMID- 14949620
TI  - [Treatment of asthma with nitrogen mustard and considerations on the nature of
      allergic diseases and dysreaction therapy].

PMID- 14949621
TI  - [Epidemic of typhoid fever in Malaga; therapeutic results of 232 cases treated
      with chloromycetin or drugs on which this antibiotic is the principal component].

PMID- 14949622
TI  - [Chromocystoscopy in the diagnosis of pyelonephritis].

PMID- 14949623
TI  - [Possibilities of radiotherapy in giant cell tumors].

PMID- 14949624
TI  - [Pulmonary embolism].

PMID- 14949625
TI  - [Considerations on a case of endogenous lymphadenobronchogenic tuberculous
      reinfection according to Schwartz].

PMID- 14949626
TI  - [Thrombosis of the inferior vena cava; clinical study].

PMID- 14949627
TI  - [Recent advances in ocular therapy].

PMID- 14949628
TI  - [Children and the problem of human rabies in Colombia].

PMID- 14949629
TI  - [Schilder's disease (cerebral atrophy and oligophrenia)].

PMID- 14949630
TI  - [Third Panamerican Congress on Pediatrics, December 2-9, 1951].

PMID- 14949631
TI  - [Preventive and therapeutic measures in infectious diseases in children].

PMID- 14949632
TI  - [Syndrome of hypofunction of the thymus].

PMID- 14949633
TI  - [Preventive and therapeutic measures in infectious diseases in children].

PMID- 14949634
TI  - [Pediatric education in Colombia].

PMID- 14949635
TI  - [Bronchial asthma in children consecutive to allergic rhinitis].

PMID- 14949636
TI  - [Perinatal mortality or feto-infantile mortality].

PMID- 14949637
TI  - [Intradermal gadusan in infants].

PMID- 14949638
TI  - [Present state of BCG vaccination].

PMID- 14949639
TI  - [Mixed form of reticuloendotheliosis; spectacular improvement with vitamin A
      shock].

PMID- 14949640
TI  - [Salmonella oregon infection in Cuba; curious epidemiological observation].

PMID- 14949641
TI  - [So-called L.E. phenomenon in lupus erythematosus].

PMID- 14949642
TI  - [Persistence of the omphalomesenteric duct].

PMID- 14949643
TI  - [Odyssey of a case of pulmonary suppuration secondary to endobronchial foreign
      body].

PMID- 14949644
TI  - [Introduction of vaccine in Cuba].

PMID- 14949645
TI  - [Associated movements or synkinesis in relation to the pyramidal syndrome].

PMID- 14949646
TI  - [Radiotherapy of cancer of the larynx].

PMID- 14949647
TI  - [Value of electroencephalography in neurological focal diagnosis].

PMID- 14949648
TI  - [Pseudotumoral encephalitis].

PMID- 14949649
TI  - [Encephalic hydatid cysts].

PMID- 14949650
TI  - [Case of streptomycin deafness].

PMID- 14949651
TI  - [Cervical tuberculosis].

PMID- 14949652
TI  - [Case of bilateral coxalgic pelvis].

PMID- 14949653
TI  - [Sulfa and penicillin in cesarean infections].

PMID- 14949654
TI  - [Analysis of one thousand cases in which rectosigmoidoscopy was used].

PMID- 14949655
TI  - [Hyperthyroidism and pregnancy].

PMID- 14949656
TI  - [Note on the classification of pulmonary carcinoma].

PMID- 14949657
TI  - [Comparative study of the duration of the vaginal effects of different estrogens
      in oil solutions].

PMID- 14949658
TI  - [Note on Phlebotomus in the region of Iguala, state of Guerrero].

PMID- 14949659
TI  - [Presentation of a case of kala-azar].

PMID- 14949660
TI  - [Case of necrotizing panarteritis with granulomatous lesions].

PMID- 14949661
TI  - [Whipple operation in adenocarcinoma of Vater's ampulla].

PMID- 14949662
TI  - [Study on hemostasis in hepatobiliary diseases].

PMID- 14949663
TI  - [Treatment of herpes zoster with ACTH and cortisone].

PMID- 14949664
TI  - [Clinical experiences with ACTH and cortisone in bronchial asthma and status
      asthmaticus].

PMID- 14949665
TI  - [Comparative study on the effect of antibiotics on Mycobacterium tuberculosis in
      vitro].

PMID- 14949666
TI  - [Anorectal fistula and cancer].

PMID- 14949667
TI  - [Cardiolipin antigen in serodiagnosis of syphilis].

PMID- 14949668
TI  - [Purpura necrotica].

PMID- 14949669
TI  - [Cutaneo-visceral and cutaneous arachnidism due to Loxosceles bite treated with
      cortisone and ACTH].

PMID- 14949670
TI  - [Santiago Ramon y Cajal].

PMID- 14949671
TI  - [Adverse reactions associated with administration of total blood; blood
      derivatives, crystalloid solutions, and simular material].

PMID- 14949672
TI  - [Report on activities of the second conference of the Psychiatric Society of
      Latin America and on the Fourth Congress World Congress on Mental Health].

PMID- 14949673
TI  - [Hemorrhage due to alterations of placental insertion].

PMID- 14949674
TI  - [Certain aspects of syphilis in Honduras].

PMID- 14949675
TI  - [Prophylactic treatment of labor and its acceleration with methergin].

PMID- 14949676
TI  - [Nomenclature of Rh factor].

PMID- 14949677
TI  - [Problem of free contracting and obtaining of medical services in the social
      security of workers].

PMID- 14949678
TI  - [Hematologic study of leprosy].

PMID- 14949679
TI  - [Newspapers publicity on supposedly wonder drugs].

PMID- 14949680
TI  - [Hiatus hernias].

PMID- 14949681
TI  - [Music and medicine; early death of Schubert].

PMID- 14949682
TI  - [Congenital gynecological conditions capable to produce sterility; surgical
      aspects].

PMID- 14949683
TI  - [Progress in the field of obstetrics in Mexico during last 50 years].

PMID- 14949684
TI  - [Principles for improving the care of patients in labor and delivery rooms in
      hospitals].

PMID- 14949685
TI  - [Principles and facilities for the care of newborn infants in hospitals].

PMID- 14949686
TI  - [Normal puerperium].

PMID- 14949687
TI  - [Vaginal trichomoniasis on pregnancy].

PMID- 14949688
TI  - [Mammary gland diseases in the newborn and gestational toxicosis].

PMID- 14949689
TI  - [Erythroblastosis fetalis treated by exchange transfusion; first case published
      in Venezuela].

PMID- 14949690
TI  - [My gynecological impression Venezuela and Cuba].

PMID- 14949691
TI  - [My obstetrical impressions in Venezuela and Cuba].

PMID- 14949692
TI  - [Intravenous iron in anemias of pregnancy].

PMID- 14949693
TI  - [Preliminary instruction in congenital heart diseases].

PMID- 14949694
TI  - [Treatment of residual cavities after pneumothorax with intrapleural injections
      of gold salts].

PMID- 14949695
TI  - [Desensitization with BCG in a case of Bazin's erythema induratum].

PMID- 14949696
TI  - [Loss of substance of the nose; correction with free chondro-cutaneous grafts
      from the ear].

PMID- 14949697
TI  - [Impressions of socialized medicine in England].

PMID- 14949698
TI  - [The future of military surgery].

PMID- 14949699
TI  - [Recreation for patients and occupational therapy first service instituted in
      military hospitals in Brazil].

PMID- 14949700
TI  - [Boerner-Jones-Luckens microflocculation reaction; comparison with Kahn and Kline
      reactions].

PMID- 14949701
TI  - [Dr. Gerardo Majella Bijos; a great pharmacist].

PMID- 14949702
TI  - [Guide to an economic history of the national pharmaceutical industry; review of
      its evolution to the appearance of the problem of primal matter].

PMID- 14949703
TI  - [Bookplates].

PMID- 14949704
TI  - [Result of the treatment of abdominal trauma].

PMID- 14949705
TI  - [Physico-chemical and biological principles of preventive measures in autogenous
      welding; application in military arsenals and plants].

PMID- 14949706
TI  - [Antigenic value of typhoid vaccine].

PMID- 14949707
TI  - [Madelung disease].

PMID- 14949708
TI  - [Treatment of bronchopulmonary fungus and yeast infections with nebulized
      gentianviolet].

PMID- 14949709
TI  - [Laboratory services in the United States Army].

PMID- 14949710
TI  - [Suggestion on requests of sanitary equipment].

PMID- 14949711
TI  - [Plastic surgery].

PMID- 14949712
TI  - [Critical study of certain methods of determination of hardness of water].

PMID- 14949713
TI  - D. Nocomedes Antelo in memoriam.

PMID- 14949714
TI  - [Antonio Mathijsen; Dutch medical officer, inventor of surgical gypsum].

PMID- 14949715
TI  - [Colonel Francisco Villa Garcia].

PMID- 14949716
TI  - [Peripheral facial paralysis].

PMID- 14949717
TI  - [Determination of urinary N. methyl nicotinamide and biochemical diagnosis of
      factor PP deficiency].

PMID- 14949718
TI  - [Not Available].

PMID- 14949719
TI  - [Blood substitutes, present state of the problem].

PMID- 14949720
TI  - [Studies on composition of the bone marrow in children; myologram in whooping
      cough].

PMID- 14949721
TI  - [Studies on composition of the bone marrow in children; myelogram in measles].

PMID- 14949722
TI  - [Studies on composition of the bone marrow in children; myelogram in scarlet
      fever].

PMID- 14949723
TI  - [Studies on composition of the bone marrow in children; myologram in diphtheria].

PMID- 14949724
TI  - [Studies on prothrombin rate by Thivolle's straight lines of correlation].

PMID- 14949725
TI  - [Colchicine in the study of proliferation of embryonic hemopoietic cells].

PMID- 14949726
TI  - [Essay on receptive heteroallergic and hypersensitive reactions in experimental
      syphilis].

PMID- 14949727
TI  - [Myocardium in experimental renal ischemia].

PMID- 14949728
TI  - [Pathogenesis of periodontolysis].

PMID- 14949729
TI  - [Functional treatment of periodontolysis; fundamental principles].

PMID- 14949730
TI  - [Filling of dental cavities with self-polymerizing resins; present status of
      scientific and experimental knowledge].

PMID- 14949731
TI  - [Considerations on the diagnosis and treatment of inversion of the occlusion of
      the incisors].

PMID- 14949732
TI  - [A contribution to the study of hereditary carbon dioxide sensitivity in
      Drosophila: an attempt at purifying the hereditary factor].

PMID- 14949733
TI  - PROCEEDINGS of the Canadian Physiological Society.

PMID- 14949734
TI  - [A new technic for white cell count and simultaneous differentiation of
      eosinophils].

PMID- 14949735
TI  - Aerobic bacteria in the intestines and slime of the pike (Esox lucius) in Lake
      Monroe, Quebec.

PMID- 14949736
TI  - [Indications for and results of arthroplasty of the hip with prosthesis in
      coxarthia].

PMID- 14949737
TI  - [Revascularization of the myocardium by arterialization of the coronary veins.
      II. Mechanism of myocardial protection after aorto-sinusoidal graft and partial
      ligature of the sinus].

PMID- 14949738
TI  - [Vessels of the lower extremity; schema and nomenclature of the venous system].

PMID- 14949739
TI  - [Diverticulosis of the small intestine].

PMID- 14949740
TI  - [Acute hemorrhagic syndromes with coagulation disorders].

PMID- 14949741
TI  - [Activation of profibrinolysin].

PMID- 14949742
TI  - [Coagulation disorders following lobectomy].

PMID- 14949743
TI  - [Fatal afibrinemis due to endothoracic surgery; pathogenic and therapeutic
      problems].

PMID- 14949744
TI  - [Fatal hemorrhagic syndromes with total incoagulability and with fibrinolysis; in
      pulmonary exeresis].

PMID- 14949745
TI  - [Fatal hemorrhagic syndromes with total incoagulability by defibrination and with
      fibrinolysis following abortion by injection of Javelle water; problem of
      defibrination in obstetrics and gynecology].

PMID- 14949746
TI  - [Fibrinolysis in certain cases of premature detachment of the placenta].

PMID- 14949747
TI  - [Fibrinolysis in pregnancy interrupted by Rh sensitivity; considerations on
      fibrinolytic hemorrhagic diathesis].

PMID- 14949748
TI  - [Postpartum fatal hemorrhagic syndrome with blood incoagulability due to probable
      fibrinolysis].

PMID- 14949749
TI  - [Heparin in medicine].

PMID- 14949750
TI  - [Coagulation time of diloted blood in mammals and in other species].

PMID- 14949751
TI  - [Application of Sternberger's method in the study of blood coagulation in man].

PMID- 14949752
TI  - [Studies on associated action of two thrombokinetic agents; brain extract
      venene].

PMID- 14949753
TI  - [Studies on associated action of two thrombokinatic agents; tissue extracts].

PMID- 14949754
TI  - [Vaccination against tetanus. I. From seroprophylaxie to anatoxic vaccination].

PMID- 14949755
TI  - [Vaccination against tetanus. II. Tetanus anatoxin and its preventive effect
      against tetanus].

PMID- 14949756
TI  - [Research on the structure of group iso-antibodies].

PMID- 14949757
TI  - [Antituberculous property of the serum of certain subject free of tuberculosis.
      (Experimental study in guinea pig)].

PMID- 14949758
TI  - [External dacryocystorhinostomy, method of choice for the rhinosurgeon].

PMID- 14949759
TI  - [Treatment of infectious otorrhea with terramycine and local chloromycetin].

PMID- 14949760
TI  - [Evolution of the therapy of malignant tumors of upper aero-digestive tract].

PMID- 14949761
TI  - [Cancer and laryngeal tuberculosis].

PMID- 14949763
TI  - [Cyst of the thyroglossal tract].

PMID- 14949762
TI  - [Crico-thyroid arthritis].

PMID- 14949764
TI  - [Chronic parotitis].

PMID- 14949765
TI  - [Treatment of pyorrhea].

PMID- 14949766
TI  - [Hemostasis in stomatology].

PMID- 14949767
TI  - [Bucco-sinusoid fistulae; surgical treatment].

PMID- 14949768
TI  - [Streptomycin intolerance].

PMID- 14949769
TI  - [A case of nephritis].

PMID- 14949770
TI  - [Diagnostic errors].

PMID- 14949772
TI  - [The dangerous universal blood donor].

PMID- 14949771
TI  - [Early diagnosis of bronchial cancer].

PMID- 14949773
TI  - [Leon Fredericq].

PMID- 14949774
TI  - [Ministry of Public Health and the Family; epidemiological report for March 9-22,
      1952].

PMID- 14949775
TI  - [Adiposity and gigantism in an adolescent].

PMID- 14949776
TI  - [Two cases of narcolepsy].

PMID- 14949777
TI  - [Therapeutic tests with a new antihistaminic with prolonged action, a derivative
      of piperazine].

PMID- 14949778
TI  - [A case of lithiasis with calcic bile].

PMID- 14949779
TI  - [Portography by transparietal splenic route; advantage in portal hypertension and
      hepatography].

PMID- 14949780
TI  - [Allergy study in the Otorhinolaryngology Clinic].

PMID- 14949781
TI  - [Value of sternal puncture in the diagnosis of chronic malaria].

PMID- 14949782
TI  - [Ayurveda].

PMID- 14949783
TI  - [Infantile bronchiectasis].

PMID- 14949784
TI  - [Preventive medical examination of infants].

PMID- 14949785
TI  - [Toxicity of synthetic insecticides].

PMID- 14949786
TI  - [Effect of hexachlorocyclohexane on mammals; biological antagonism].

PMID- 14949787
TI  - [Toxicity of some new synthetic insecticides].

PMID- 14949788
TI  - [Dispersal and transport of noxious insects].

PMID- 14949789
TI  - [A Burmese winter].

PMID- 14949790
TI  - [Reflections on prognosis].

PMID- 14949791
TI  - [Present day subacute encephalitis].

PMID- 14949792
TI  - [On several new physiotherapeutic procedures; diadynamic current, micro-waves,
      and ultrasounds].

PMID- 14949793
TI  - [On two cases of measles encephalitis with psychic disorders].

PMID- 14949794
TI  - [The commemoration of Dr. Jean-Pierre Maunoir on amputations].

PMID- 14949795
TI  - [Reflections on prognosis].

PMID- 14949796
TI  - [Indication for surgical Pact].

PMID- 14949797
TI  - [Functional explanation of the kidney; classical examples and recent
      acquisitions].

PMID- 14949798
TI  - [Two cases of cerebral hemorrhage (aneurysmal rupture; spontaneous subcortical
      hematoma) and their neurosurgical treatment].

PMID- 14949799
TI  - [Dr. Charles De Montet (1881-1951)].

PMID- 14949800
TI  - [Theodore Stephani (1868-1951)].

PMID- 14949801
TI  - [Two cases of pulmonary abscess].

PMID- 14949802
TI  - [Humoral equilibrium in apomorphine treatment of chronic alcoholism].

PMID- 14949803
TI  - [Pyloric stenosis caused by toxic gastritis].

PMID- 14949804
TI  - [Sudden death in adults].

PMID- 14949805
TI  - [Relation of infectious mononucleosis to diptheria and atypical pneumonia].

PMID- 14949806
TI  - [Morphological studies of the Koch bacillus and its multiplication].

PMID- 14949807
TI  - [Eosinophil band pneumonosis in newborn (hyaline membrane pneumonia)].

PMID- 14949808
TI  - [Prolapse of the mucosa across the pylorus].

PMID- 14949809
TI  - [Herpetic encephalitis in the newborn].

PMID- 14949810
TI  - [Significance of serum pathology in suprareno-hepatic regulation; application to
      new therapeutic method].

PMID- 14949811
TI  - [The liver and estrogen metabolism].

PMID- 14949812
TI  - [Progress of the study of hepato-endocrine relationship].

PMID- 14949813
TI  - [Studies of cerebral lesions and anoxia in respiratory paralysis].

PMID- 14949815
TI  - [Presidential address].

PMID- 14949814
TI  - [Address of the ex-president].

PMID- 14949816
TI  - [Algetic and vasomotor reflex disorders of two index fingers following localized
      minimal trauma of one; concomitant cervical arthritis].

PMID- 14949817
TI  - [Two complications after carbon monoxide poisoning; transitory Parkinson's
      syndrome with inertia and mutism and chronic chorea].

PMID- 14949818
TI  - [Surgical treatment of carotido-cavernous aneurysm].

PMID- 14949819
TI  - [Three new cases of Mill's syndrome of cerebral origin].

PMID- 14949820
TI  - [Internal dolichocarotid].

PMID- 14949821
TI  - [Intraspinal tumor extended to the second cervical and fourth dorsal vertebrae;
      cure].

PMID- 14949822
TI  - [Thrombophlebitis of the vein of Galien; hemorrhage of the central gray nuclei
      and of the epiphysis].

PMID- 14949823
TI  - [Spasmodic torticollis consecutive to traumatic cortical lesion; favorable
      results after excision of cortical lesion].

PMID- 14949824
TI  - [Early radiodiagnosis of tumor of the jugular glomus].

PMID- 14949825
TI  - [Need for cardiazol activation for electroencephalographic detection of certain
      cerebral tumors].

PMID- 14949826
TI  - [Epileptic syndromes in cerebral abscess treated by ablation or by aspiration].

PMID- 14949827
TI  - [Impacted teeth indicative of cleidocranial dysostosis].

PMID- 14949828
TI  - [Presence of teeth in dermoid cysts of the ovary].

PMID- 14949829
TI  - [The oral forms of benign inoculation lymphoreticulosis or cat-scratch disease or
      Debre-Mollaret disease].

PMID- 14949830
TI  - [Subacute evolution of a disease of a lymph node of the neck: benign inoculation
      lymphoreticulosis].

PMID- 14949831
TI  - [Allergic reactions of oral origin].

PMID- 14949832
TI  - [Penicillin in maxillofacial surgery].

PMID- 14949833
TI  - [Dental caries, a collagen disease].

PMID- 14949834
TI  - [Crenotherapy and periodontitis].

PMID- 14949835
TI  - [Functional restoration in dentistry].

PMID- 14949836
TI  - [Psycho-physio-pathology of tinnitus].

PMID- 14949837
TI  - [Neurological diagnosis of certain types of oculomotor paralysis].

PMID- 14949838
TI  - [Oto-neuro-ophthalmological disorders due to brain abscess of difficult
      etiological diagnosis].

PMID- 14949839
TI  - [Prismatic glasses in the treatment of vertigo].

PMID- 14949840
TI  - [Cataplexic crisis and pupillary disorders].

PMID- 14949841
TI  - [Considerations on oculomotor vertical paralysis].

PMID- 14949842
TI  - [Acute bilateral optic neuritis following ethmoiditis].

PMID- 14949843
TI  - [Paralysis of accommodation in mumps].

PMID- 14949844
TI  - [Symptomatologic value of cataract in Steinert's myotonic dystrophy].

PMID- 14949845
TI  - [Bonnet, Dechaume, and Blanc syndrome; cirsoid aneurysm of the retina associated
      with central lesions].

PMID- 14949846
TI  - [Rose' kopf-tetanus; cure].

PMID- 14949847
TI  - [Intermediary laryngeal diplegia with aphonia in cancer of the cervical cancer].

PMID- 14949848
TI  - [Supra sellar cholesteatoma].

PMID- 14949849
TI  - [Investigation on equilibrium disorders and studies on vestibular tests in
      frontal lesions produced by psychosurgery; preliminary note].

PMID- 14949850
TI  - [Scoliosis of ocular origin].

PMID- 14949851
TI  - [Photomotor reflex in retrolental fibroplasia].

PMID- 14949852
TI  - [Case of angioma of the left Rolando's cerebral region].

PMID- 14949853
TI  - [Osteitis fibrosa cystica of the petrous bone].

PMID- 14949854
TI  - [Evaluation of quinine].

PMID- 14949855
TI  - [Doctor Ch. W. F. Winckel, a scientist of international importance].

PMID- 14949856
TI  - [Mentality of malaria patients and modality of quinine therapy].

PMID- 14949857
TI  - [Plombage with acrylic balls in surgical collapsotherapy; studies on results in
      122 cases].

PMID- 14949858
TI  - [Study on tuberculous primary infection; the concept of inoculation chancre and
      external approach].

PMID- 14949859
TI  - [Constricted and displaced cavity; indication of choice for phrenicotripsy].

PMID- 14949860
TI  - [Vitamin B1, vitamin B2, and vitamin PP level in streptomycin therapy of
      pulmonary tuberculosis].

PMID- 14949861
TI  - [Concept of abortive tuberculosis].

PMID- 14949862
TI  - [Research and considerations on the tonus and balance of the mediastinum].

PMID- 14949864
TI  - [Vaporization bronchography].

PMID- 14949863
TI  - [Dr. Derscheid, 1871-1952].

PMID- 14949865
TI  - [Agminated pulmonary tuberculosis, remote sequels of primary infection].

PMID- 14949866
TI  - [Continuous aeration and treatment in sanatoria].

PMID- 14949867
TI  - [Organization of control of tuberculosis in Turkey].

PMID- 14949868
TI  - [Leon Bourgeois and his works in the field of tuberculosis].

PMID- 14949869
TI  - [Regression of secondary complications to sections of pleural bridles].

PMID- 14949870
TI  - [Modes of action of different methods of thoracoplasty; advantages and
      disadvantages].

PMID- 14949871
TI  - [Prognosis and evolution of syndromes of tuberculous impregnation according to
      data on 137 cases].

PMID- 14949872
TI  - [Study on tuberculous primary infection; the concept of inoculation chancre and
      external approach].

PMID- 14949873
TI  - [Osteoarticular tuberculosis consecutive to miliary tuberculosis treated with
      streptomycin].

PMID- 14949874
TI  - [Tuberculomas and persistant casseous foci; anatomo-clinical study].

PMID- 14949875
TI  - [Prevention of tuberculosis in Finland].

PMID- 14949876
TI  - [Nodular tuberculosis of the superior pulmonary regions and its therapy].

PMID- 14949877
TI  - [Streptomycin and adenectomies].

PMID- 14949878
TI  - [Tuberculosis and anal fistula].

PMID- 14949879
TI  - [Possibilities of horizontal radiotomy in radiological diagnosis of pulmonary
      tuberculosis].

PMID- 14949880
TI  - [Latent abdominal effusions in therapeutic pneumoperitoneum].

PMID- 14949881
TI  - [Encephalopathies during streptomycin therapy].

PMID- 14949882
TI  - [Qualification of specialists in pneumophthisiology].

PMID- 14949883
TI  - Physical methods in the management of arthritis in childhood.

PMID- 14949884
TI  - Some observations on the aetiology of the diseases of adaptation.

PMID- 14949885
TI  - Trigger point syndrome.

PMID- 14949886
TI  - The psychiatrist and the public.

PMID- 14949887
TI  - Multiple myeloma.

PMID- 14949888
TI  - Diagnosis and treatment of early carcinoma of the cervix.

PMID- 14949890
TI  - ANNUAL reports, the Rhode Island Medical Society.

PMID- 14949889
TI  - Don't let it get under your skin; some observations of psychosomatic dermatology.

PMID- 14949891
TI  - [Progress in the field of pharmacotherapy of neoplasms].

PMID- 14949892
TI  - [Experimental study on the effect of hirudin on the factors of blood
      coagulation].

PMID- 14949893
TI  - [Intradermoreaction with Reiter's treponemic antigen in diagnosis of syphilis].

PMID- 14949894
TI  - [Plan for a ballistocardiograph].

PMID- 14949895
TI  - [Spontaneous subclavian aneurysms with special reference to surgical treatment;
      report of a case of syphilitic etiology with surgical extirpation].

PMID- 14949896
TI  - [Studies on spectral composition of fluorescence of blood iron in catarrhal and
      constitutional hemolytic jaundice].

PMID- 14949897
TI  - [Therapy of Duhring's dermatitis].

PMID- 14949898
TI  - [Densimetric test of urine; its value and signification in renal function tests].

PMID- 14949899
TI  - [Study on perineal testicular ectopy].

PMID- 14949900
TI  - [Pathological variations of protein level].

PMID- 14949901
TI  - [Extrarenal hyperazotemia].

PMID- 14949902
TI  - [Effect of progressive dosage of adrenalin on urinary elimination of 17
      ketosteroids].

PMID- 14949903
TI  - [Phillips' and Van Slyke's method; technic and general considerations].

PMID- 14949904
TI  - [Case of multiple localization of otogenous cerebral abscesses].

PMID- 14949905
TI  - [Preliminary notes on value of isonicotinic acid hydrazide in the treatment of
      tuberculosis].

PMID- 14949906
TI  - [Ballistocardiographic study; ballistocardiography in normal subjects].

PMID- 14949907
TI  - [Produced urobilinuria; preliminary observations and considerations].

PMID- 14949908
TI  - [Physiopathology of venous circulation in varices; peripheral venous pressure and
      circulation rate following saphenectomy].

PMID- 14949909
TI  - [Clinical and statistical observations on 238 cases of acute hepatitis].

PMID- 14949910
TI  - [Hazards in use of testosterone in urology].

PMID- 14949911
TI  - [Rapidity of recovery of blood in professional blood-donors; efficacy of
      administration of hemopoietic horse serum].

PMID- 14949912
TI  - [Observations on 8 cases of pulmonary tuberculosis treated with isonicotinic acid
      hydrazide during 30 days].

PMID- 14949913
TI  - [Hemostatic effect of transfusion of autogenous blood in prostatectomized].

PMID- 14949914
TI  - [Isolation of two strains of virus in a focus of epidemic of influenza in Venafro
      (Molise) in January, 1952].

PMID- 14949915
TI  - [Ballistocardiographic studies; ballistocardiography in heart diseases].

PMID- 14949916
TI  - [Unusual traumatic complication; migration of the testis into the acetabular
      cavity].

PMID- 14949917
TI  - [Associated steroids-ascorbic acid in certain chronic arthropathies].

PMID- 14949918
TI  - [Shadows of physicians in Divine Comedy].

PMID- 14949919
TI  - [Rapid therapeutic action of isonicotinic acid hydrazide in grave oropharyngo
      laryngeal tuberculosis].

PMID- 14949920
TI  - [Target cells in various hematological conditions in Colley's anemia].

PMID- 14949921
TI  - [Ancylostomiasis in Puglia, preliminary note].

PMID- 14949922
TI  - [Considerations on pericardial cysts and diverticula].

PMID- 14949923
TI  - [Effect of androstendiol on glycide metabolism].

PMID- 14949924
TI  - [New therapeutic methods in Basedow's disease].

PMID- 14949925
TI  - [Psychosurgery; scientific-practical, moral, and juridical aspects].

PMID- 14949926
TI  - [Physiopathology of pulmonary arterious circulation].

PMID- 14949927
TI  - [Biochemistry of the myocardium and its physiopathological and clinical
      significance; electrolytes].

PMID- 14949928
TI  - [Biochemistry of the myocardium and its physiopathological and clinical
      significance; enzymes, vitamins, and hormones].

PMID- 14949929
TI  - [Biochemistry of the myocardium and its physiopathological and clinical
      significance; certain diagnostic and therapeutic problems].

PMID- 14949930
TI  - [Fibrositis and associated pathological conditions].

PMID- 14949931
TI  - [Problem of cortisone in rheumatology].

PMID- 14949932
TI  - [Arthrosis deformans of the hip, problems and possibilities of orthopedic
      surgery].

PMID- 14949933
TI  - [Leonardo and anatomy].

PMID- 14949934
TI  - [Development and treatment of gastrojejunal functional syndromes secondary to
      gastric resection].

PMID- 14949935
TI  - [Preliminary results of the treatment of pulmonary tuberculosis with isonicotinic
      acid hydrazide].

PMID- 14949936
TI  - [Value of cytological examination of sputum in diagnosis of pulmonary cancer].

PMID- 14949937
TI  - [Roentgen and radium therapy record].

PMID- 14949938
TI  - [Spectroscopic examination of fluorescence of the normal human bile].

PMID- 14949939
TI  - [Prevention of tuberculosis in Turkey].

PMID- 14949940
TI  - [Clinical observations and experimental and comparative pathology; relations,
      accomplishments, and prospectives].

PMID- 14949941
TI  - [ACTH and eosinophil leukemia].

PMID- 14949943
TI  - [Flaviano Magrassi].

PMID- 14949942
TI  - [Variations of Schilling and Arneth formulas following antibiotic therapy].

PMID- 14949944
TI  - [Epicrisis of a case of pulmonary, peritoneal, and adnexal tuberculosis during
      isonicotilhydrazide therapy].

PMID- 14949945
TI  - [Relation between blood proteins fractions and cytological composition of the
      bone marrow in chronic arthropathies].

PMID- 14949946
TI  - [Parathyroid function following surgical intervention on the antero-lateral
      region of the neck].

PMID- 14949947
TI  - [Aspiration liver biopsy and local aureomycin in a case of amebic liver abscess;
      cure].

PMID- 14949948
TI  - [Case of chronic pemphigus vulgaris treated with aureomycin, italchine, and gamma
      globulin].

PMID- 14949949
TI  - [Public Health Administration in the U.S.A..].

PMID- 14949950
TI  - [Development of the reproductive system of the brown trout in normal conditions
      and the effect of steroid hormones].

PMID- 14949951
TI  - [Intervention of ACTH and adrenal cortex hormones in the genesis of fatty liver].

PMID- 14949952
TI  - [Closing devices in arteries of the excretory apparatus of the kidney].

PMID- 14949953
TI  - [Interaction of estrogens and androgens; bibliography and experiments].

PMID- 14949954
TI  - [Analogy of structure and obliteration mechanism of the ductus arteriosus and the
      umbilical arteries in mammals].

PMID- 14949955
TI  - [Possibility of crossing of the Culex pipiens L with Culex autogenicus R].

PMID- 14949956
TI  - [Effect of prolactin on the male gonads in the hypophysectomized rat].

PMID- 14949957
TI  - [An interesting soil zygomic zygomycete, Gongronella urceolifera, n. gen. et n.
      sp..].

PMID- 14949958
TI  - [Mesomucinases in medico-surgical thoraco-pleural complications of pulmonary
      tuberculosis].

PMID- 14949959
TI  - [Considerations on a case of muscular echinococcal cyst].

PMID- 14949960
TI  - [Case of sarcoma of the lesser omentum].

PMID- 14949961
TI  - [So-called lyphagic granuloma of the gallbladder and interstitial genesis of
      calculi; clinical study].

PMID- 14949962
TI  - [Cutaneous and subcutaneous lesions in appendicitis and in initial chronic
      cholecystitis].

PMID- 14949963
TI  - [Protective action of cystine in chloroform poisoning].

PMID- 14949964
TI  - [Local application of fresh placenta in the treatment of post-gastrectomy
      fistulas of the duodenal stump].

PMID- 14949965
TI  - [Phosphatases in gastric juice].

PMID- 14949966
TI  - [Gastric juice phosphatases in cancer of the stomach].

PMID- 14949967
TI  - [Studies on gastric secretion; reaction of hydrochloric acid secretion to
      stimulation of the vegetative nervous system in pathological conditions].

PMID- 14949968
TI  - [Certain characteristics of gastric secretion in liver cirrhosis].

PMID- 14949969
TI  - [Studies on gastric secretion; excito-secretion consecutive to vagal inhibition
      with atropine and ergotamine].

PMID- 14949970
TI  - [Sodium chloride balance in liver cirrhosis].

PMID- 14949971
TI  - [Odontoiatric education in Italy].

PMID- 14949972
TI  - [Sympathetic function in stomatology].

PMID- 14949973
TI  - [Maxillo-dental abnormalities in cleidocranial dysostosis].

PMID- 14949974
TI  - [Total iron, spleen iron, and liver iron; its relation to hemoglobinemia in
      repeated anoxia in rabbits].

PMID- 14949975
TI  - [Effect of methionine on the resistance in experimental anoxia and on related
      liver diseases].

PMID- 14949976
TI  - [Effect of oxygen on the power of fusion of retinal images].

PMID- 14949978
TI  - [Ballistocardiography].

PMID- 14949977
TI  - [Experimental study on renal histopathology in anoxia].

PMID- 14949979
TI  - [Surgical treatment of mitral stenosis].

PMID- 14949980
TI  - [The United Nations medical services in the Korean conflict].

PMID- 14949981
TI  - [XIII International Congress on Military Medicine and Pharmacy, Paris, 17-23
      June, 1951].

PMID- 14949982
TI  - The medical problems of flying.

PMID- 14949983
TI  - [Indications and contraindications for aerial transportation of wounded and
      sick].

PMID- 14949984
TI  - [Motor neuroses; nosological aspects and narcoanalytic therapy].

PMID- 14949985
TI  - [Case of radicular paralysis of the brachial plexus consecutive to gun-shot wound
      of the arm; clinical and medicolegal considerations].

PMID- 14949986
TI  - [Cerebral double ganglioneuroma].

PMID- 14949987
TI  - [Data on the surface of section of the cerebral ventricles and of the sella
      turcica in epilepsy].

PMID- 14949988
TI  - [Barbiturate subnarcosis in identification of organic psychopathies].

PMID- 14949989
TI  - [Various forms of development of tumors of the neuroglia].

PMID- 14949990
TI  - [Intracranial neurysms].

PMID- 14949991
TI  - [Comparison of the brain with an electric machine].

PMID- 14949992
TI  - [Considerations on two cases of craniopharyngioma with total extirpation of one].

PMID- 14949993
TI  - [Electroencephalography in aged].

PMID- 14949994
TI  - [Cysts of the third ventricle with psychical symptomatology and without
      hypertensive manifestations].

PMID- 14949995
TI  - [Case of polyneuritis in pregnancy; anatomical and clinical study of
      polyradiculoneuritis].

PMID- 14949996
TI  - [Average values, groups differences, and specific deficiencies in 100 mental
      patients examined with verbal tests].

PMID- 14949997
TI  - [Myxoma of the medio-posterior cranial fossa].

PMID- 14949998
TI  - [Psychical disorders in tuberculous meningitis].

PMID- 14949999
TI  - [Neurological syndromes following serotherapy; clinical aspects].

PMID- 14950000
TI  - [Electrocorticographic localization of temporal epileptogenic foci].

PMID- 14950001
TI  - [Theoretical considerations and results in practice of dinitrile therapy of
      certain psychoses].

PMID- 14950002
TI  - [Current physiotherapy problems in cancer of the uterine portio. Part II].

PMID- 14950003
TI  - [Appendicitis in obstetrics and gynecology].

PMID- 14950004
TI  - [Cerebral edema arising in puerperium in a subject with diencephalic-hypophysial
      dystrophic characteristics].

PMID- 14950005
TI  - [Relations between drugs affecting the uterus and heart; oxytocic power of a new
      heart stimulant, tevetina].

PMID- 14950006
TI  - [A case of vestibular anus].

PMID- 14950007
TI  - [Physiological icterus in newborn infant, Rh factor and ABO blood group system].

PMID- 14950008
TI  - [Large vesico-vaginal fistula caused by foreign body in vagina; operation and
      recovery].

PMID- 14950009
TI  - [Technical preparation for obstetrical and infant nursing; Institute of Medical
      and Obstetrical Guidance].

PMID- 14950010
TI  - [Basal temperature and the ovarian cycle].

PMID- 14950011
TI  - [Current physiotherapy problems in cancer of the uterine porilo. Part III].

PMID- 14950012
TI  - [Primary carcinoma of the fallopian tube].

PMID- 14950013
TI  - [A case of intracerebral hematoma originating in labor; surgery].

PMID- 14950014
TI  - [Pregnenolone metabolism in normal and cancerous subject].

PMID- 14950015
TI  - [Extraperitoneal abdominal Caesarean section].

PMID- 14950016
TI  - [Behavior of bilirubinemia during Diamond exsanguinotransfusion for fetal
      erythroblastosis].

PMID- 14950017
TI  - [Blood group and Rh factor in pregnancy toxemias].

PMID- 14950018
TI  - [Effect of acetylcholine on functional amenorrhea].

PMID- 14950019
TI  - [For equal recognition of university and hospital obstetrical service].

PMID- 14950020
TI  - [Activity of the Department in the first four years of its functioning].

PMID- 14950021
TI  - [Case of uterine carcinosarcoma].

PMID- 14950022
TI  - [Omental echinococcosis simulating residual ovarian cyst].

PMID- 14950023
TI  - [Renal serous cysts simulating ovarian cysts].

PMID- 14950024
TI  - [Prognostic value of cardiovascular Rehn's test in operative gynecology].

PMID- 14950025
TI  - [Use of curare in delivery].

PMID- 14950026
TI  - [Hormonal study of vesicular mole and chorioepithelioma].

PMID- 14950027
TI  - [Differential diagnosis of extrauterine pregnancy].

PMID- 14950028
TI  - [Clinico-statistical considerations on podalic delivery].

PMID- 14950029
TI  - [Case of postoperative fibrile acute delirium].

PMID- 14950030
TI  - [Right and left ampullar tubel extrauterine pregnancies with nine year interval
      consecutive to insufflation].

PMID- 14950031
TI  - [Cerebrospinal meningitis in labero and puerperium].

PMID- 14950032
TI  - [Study of a case unusual internal hernia].

PMID- 14950033
TI  - [Streptokinase in coagulated blood from hemorrhage in extrapleural pneumothorax].

PMID- 14950034
TI  - [Effect of Vipera aspis venom associated with chloramphenicol on Escherichia coli
      and on Micrococcus pyogenes aureus].

PMID- 14950035
TI  - [Acute chronic appendicitis with secondary ileal, cecal, and meso-appendiceal
      volulus].

PMID- 14950036
TI  - [Ante-partum diagnosis of anencephalic monsters].

PMID- 14950037
TI  - [Effect of pteroylmonoglutamic and pteroyltriglutamic acids on the ovary].

PMID- 14950038
TI  - [Pancreatic pseudocysts; clinical study].

PMID- 14950039
TI  - [Osteochondromatosis; considerations on familial aspects].

PMID- 14950040
TI  - [The Donaggio inhibition phenomenon as a manifestation of the general adaptation
      syndrome].

PMID- 14950041
TI  - [Cholinesterase activity in the physiopathology of the nervous system].

PMID- 14950042
TI  - [Rare case of malignant Erdheim tumor with remote metastases].

PMID- 14950043
TI  - [Case of traumatic intradural hematoma; clinical, angiographic and
      electroencephalographic study].

PMID- 14950044
TI  - [Localization of function in cerebral cortex].

PMID- 14950045
TI  - [A familial oto-oculo-psychiatric syndrome].

PMID- 14950046
TI  - [Ethical endowment of senile psychotics and paralytics].

PMID- 14950047
TI  - [Hepatocerebral degeneration: Westphal-Strumpeli pseudosclerosis; Wilson's
      disease; hepatolenticular degeneration; abdominal Wilson's disease].

PMID- 14950048
TI  - [Zosterian encephalitis].

PMID- 14950049
TI  - [Cervico-brachial neuralgia].

PMID- 14950050
TI  - [Surgical treatment of epilepsy, with special reference to electrocorticography].

PMID- 14950051
TI  - [Relation between subacute anterior poliomyelitis and amyotrophic lateral
      sclerosis; anatomoclinical reports].

PMID- 14950052
TI  - [Effect of intravenous novocain on the rabbit brain; experimental study].

PMID- 14950053
TI  - [The neuroglia of the optic nerve and optic chiasma].

PMID- 14950054
TI  - [Concept and limitations of the problem of metastases of intracranial tumors;
      critical review and personal contribution].

PMID- 14950055
TI  - [Great figures of Italian clinical medicine of the last century].

PMID- 14950056
TI  - [Larghi and Ollier].

PMID- 14950057
TI  - [Jacopo da Sanginesio, archphysician of Popes Sixtus IV and Innocent VIII].

PMID- 14950058
TI  - [Surgeons and surgery in t the 18th century in a letter from the College of
      Physicians of Bologna to the Academy of Medicine of Paris].

PMID- 14950059
TI  - [Case of indigestion in Cicero].

PMID- 14950060
TI  - [Historical documents of the 1st International Health Conference].

PMID- 14950061
TI  - [Historical note on aid to the war injured and sick].

PMID- 14950062
TI  - [Surgery in Czechoslovakia in unified medicine].

PMID- 14950063
TI  - [Management of anesthesia].

PMID- 14950064
TI  - [New automatic value for control of respiration in single stage operations].

PMID- 14950065
TI  - [Hazards in general anesthesia].

PMID- 14950066
TI  - [Present problems in the field of anesthesia].

PMID- 14950068
TI  - [Not Available].

PMID- 14950067
TI  - [Standardization of anesthesiological terminology].

PMID- 14950069
TI  - [Clinical and statistical data on blood donors exposed to numerous donations].

PMID- 14950070
TI  - [Determination of prothrombin time with hemostatic R. C..].

PMID- 14950071
TI  - [Reticulosis, reticuloendotheliosis, and reticulosarcoma].

PMID- 14950073
TI  - [Anticoagulant therapy].

PMID- 14950072
TI  - [ACTH and cortisone in hematology].

PMID- 14950074
TI  - [Fibrinolysis].

PMID- 14950075
TI  - [Plethysmography of the human brain].

PMID- 14950076
TI  - [Certain plethysmographic reactions of the brain and the fingers in men].

PMID- 14950077
TI  - [Effect of histamine on conditioned reflex of the cerebral vessels].

PMID- 14950078
TI  - [Experience with toxicity of cyclohexanonoxyme, epsilon-caprolactam, and epsilon
      aminocaproic acid; biological equalization of all substance].

PMID- 14950079
TI  - [Development of the Pavlovian theory in the field of physiology and pathology of
      nutrition].

PMID- 14950080
TI  - [Present state of gastroenterology and nutrition].

PMID- 14950081
TI  - [Cholecystographic paradox].

PMID- 14950082
TI  - [Chronic recurrent pancreatitis].

PMID- 14950083
TI  - [Respectives of research in the field of peptic ulcer].

PMID- 14950084
TI  - [Changes of protein metabolism in peptic ulcer; electrophoretic study].

PMID- 14950085
TI  - [Liver function disorders in peptic ulcer].

PMID- 14950086
TI  - [Course of alimentary glycemia in peptic ulcer].

PMID- 14950087
TI  - [Electrocardiographic control of patients with peptic ulcer treated with
      prolonged sleep].

PMID- 14950088
TI  - [Results of surgical therapy of peptic ulcer].

PMID- 14950089
TI  - [Primary cancer of the stump following resection of the stomach].

PMID- 14950090
TI  - [Evaluation of conditions following surgery of gastroduodenal ulcer].

PMID- 14950091
TI  - [Gastric pain with special reference to surgical treatment of peptic ulcer].

PMID- 14950092
TI  - [Lymphosarcoma penetrating the gastric wall as a cause of repeated melanae,
      hematemesis, and transdiaphragmatic gastropleural fistula].

PMID- 14950093
TI  - [Hepatodiaphragmatic interposition of the hepatic flexure of the transverse colon
      following indicated division of the phrenic nerve].

PMID- 14950094
TI  - Influence of probenecid on serum penicillin concentration after oral
      administration of penicillin.

PMID- 14950095
TI  - Electrophoretic studies of plasma proteins in severe infantile gastroenteritis.

PMID- 14950096
TI  - A method for localization and determination of serum lipids after
      electrophoretical separation on filter paper.

PMID- 14950097
TI  - The serum proteins in rheumatic diseases.

PMID- 14950098
TI  - The accuracy of basal metabolism determination in the clinical laboratory.

PMID- 14950099
TI  - Cholesterol studies. I. The cholesterol content of foods.

PMID- 14950100
TI  - Cholesterol studies. II. Dietary cholesterol and atherosclerosis.

PMID- 14950101
TI  - Turbidimetric determination of diastase in urine with dextrin as substrate.

PMID- 14950102
TI  - Comments on the determination of para-aminosalicylic acid (PAS) with
      dimethylaminobenzaldehyde.

PMID- 14950103
TI  - Pulmonary and tissue gaseous nitrogen elimination resulting from; 1.
      Hyperventilation breathing air 2. Breathing oxygen normally.

PMID- 14950104
TI  - On the technique of eosinophil counting.

PMID- 14950105
TI  - [Schizophrenia & mercury poisoning. Contribution to the study of the
      schizophreniforme psychoses due to mercury].

PMID- 14950106
TI  - [Synkinesis].

PMID- 14950107
TI  - [3 cases of rare inferior oblongata syndrome (hemiplegia curuciata & hemiplegia
      alternans infima) with a contribution to the knowledge of the course of the
      fibers in the decussatio pyramidum & lemniscus].

PMID- 14950108
TI  - [Therapeutic use of electronarcosis in chronic psychoses].

PMID- 14950109
TI  - [Personality & life situation of 130 compensation neurotics].

PMID- 14950110
TI  - [Some neuro-psychiatric experiences in connection with electroshock therapy].

PMID- 14950111
TI  - [Cerebral focal symptoms caused by ascaridiasis].

PMID- 14950112
TI  - [Acromegaly & trauma].

PMID- 14950113
TI  - [Hypertrophic ossifications of the carotid artery].

PMID- 14950114
TI  - [Pathogenesis & therapy of delirium tremens & pathologic intoxication].

PMID- 14950115
TI  - [Not Available].

PMID- 14950116
TI  - [Not Available].

PMID- 14950117
TI  - [Not Available].

PMID- 14950118
TI  - [Not Available].

PMID- 14950119
TI  - [The meaning of the terms normal & abnormal, healthy & sick in psychiatric
      evaluation].

PMID- 14950120
TI  - [Studies on schizophrenia].

PMID- 14950121
TI  - [Proposal for classification of psychiatry & theory of neuroses].

PMID- 14950122
TI  - [Contribution to the study of the disorders of carbohydrate metabolism in mental
      disorders; diabetes & psychoses].

PMID- 14950123
TI  - [EEG in character & behavior disorders of children].

PMID- 14950124
TI  - [The body image of neurology].

PMID- 14950125
TI  - [The plasticity of the nervous system, its nature, history & clinical
      application].

PMID- 14950126
TI  - [Contribution to the study of the syndrome of sensomotor induction].

PMID- 14950127
TI  - [Maligne familial myoclosus epilepsy].

PMID- 14950128
TI  - [Results of systematic investigations on the cause of temporary increase of
      neurological complications of diphtheria].

PMID- 14950129
TI  - [Psychology of the crimes against life].

PMID- 14950130
TI  - [Right-handedness].

PMID- 14950131
TI  - [Not Available].

PMID- 14950132
TI  - [Forms & variations of epilepsy].

PMID- 14950133
TI  - [Experimental investigations on epilepsy].

PMID- 14950134
TI  - [Methods of provocation in epilepsy].

PMID- 14950135
TI  - [Technique & clinical application of the activated EEG].

PMID- 14950137
TI  - [Histopathological investigations on myoclonus epilepsy].

PMID- 14950136
TI  - [The problem of surgical treatment of focal epilepsies].

PMID- 14950138
TI  - [Enlarged indication for angiography in aneurysms of the anterior part of the
      circulus Willisii].

PMID- 14950139
TI  - [Palliative surgery in radiculitis due to cervical spondylosis or ruptured disc].

PMID- 14950140
TI  - [Not Available].

PMID- 14950141
TI  - [Toxoplasma encephalitis of dog].

PMID- 14950143
TI  - [Not Available].

PMID- 14950142
TI  - [Glycogen body of the spinal cord of birds].

PMID- 14950144
TI  - [Not Available].

PMID- 14950145
TI  - [Not Available].

PMID- 14950146
TI  - [Ideas on the improvement of our mental hospitals].

PMID- 14950147
TI  - [Evolution of mental diseases in the Swiss psychiatric hospitals].

PMID- 14950148
TI  - [Contribution of a country psychiatrist to the question of further development of
      mental hospitals].

PMID- 14950149
TI  - [Principles of the building and function of psychiatric hospitals].

PMID- 14950150
TI  - [Duties of the director of a mental hospital].

PMID- 14950151
TI  - [Steroids and growth. Effect of natural bile acids].

PMID- 14950152
TI  - [Plasmacellular myeloma with special consideration of its combination with
      reticulosarcoma].

PMID- 14950153
TI  - [Effects of desoxycorticosterone vitamin C and cortisone on the formalin
      arthritis of the rat].

PMID- 14950154
TI  - [Attempts of artificial infection of the swine louse Haematopinus suis L. with
      Rickettsia prowazeki and rickettsia quintana].

PMID- 14950155
TI  - [Glomeruloscleroses caused by carbon disulfide].

PMID- 14950156
TI  - [Bacteriolysis of a strain of bacillus cereus; evidence in electronic
      microscopy].

PMID- 14950157
TI  - [Hemorrhagic postvaccinal encephalomyelitis].

PMID- 14950158
TI  - [The problem of the so-called neurovegetative pulmonary tonus].

PMID- 14950159
TI  - [The action of the thiosemicarbazones].

PMID- 14950160
TI  - [Spirometric observations of tuberculous caverns of the lung and relation between
      spirometric values and the stratigraphic and cavernographic picture].

PMID- 14950161
TI  - [Primary tuberculosis in identical twins; casuistic contribution].

PMID- 14950162
TI  - [On kerato-conjunctivitis scrofulosa in infant and its significance for general
      tuberculosis].

PMID- 14950163
TI  - Electron microscopy of chromosomes in smears.

PMID- 14950164
TI  - Fatal Trypanosoma cruzi infection in the white rat.

PMID- 14950165
TI  - The action of some water-soluble poly-alpha-amino acids on fibrinolysis.

PMID- 14950166
TI  - Action of penicillin on streptococci; enhancement of sensitivity in vivo?

PMID- 14950168
TI  - The Scientific Council on Problems of the Physiological Theory of Academician I.
      P. Pavlov; a study in control.

PMID- 14950167
TI  - The detection of crystals following local injection of cortisone and compound F
      into the skin of man.

PMID- 14950169
TI  - Conjugation Tetrahymena.

PMID- 14950170
TI  - Some oxidation products of DL-alpha-tocopherol obtained with ferric chloride.

PMID- 14950171
TI  - An egg encrusted with protoporphyrin.

PMID- 14950172
TI  - The accelerating effect of calcium on the fibrinogen fibrin transformation.

PMID- 14950173
TI  - Enzymatic cytolysis of epithelium by filtrates of feces from patients with
      ulcerative colitis.

PMID- 14950174
TI  - Effect of p-chlorophenoxyacetic acid (CIPA) and 3-indolacetic acid (IA) on
      certain dehydrogenase systems of the tomato fruit, L. esculentum.

PMID- 14950175
TI  - Carbon-carbon bond lengths.

PMID- 14950176
TI  - Geometric deviations in the growth of tissue cultures.

PMID- 14950177
TI  - Microbial selection.

PMID- 14950178
TI  - Disease resistance and early testing of maize.

PMID- 14950179
TI  - Chemical constitution and biological activity of some organophosphorus compounds.

PMID- 14950180
TI  - The recording of flight movements in insects.

PMID- 14950181
TI  - Analysis of growth of the chick marginal blastoderm.

PMID- 14950183
TI  - Inbred strains of Culex mosquitoes.

PMID- 14950182
TI  - On the nature of the so-called background material in estrogen fractions of
      extracts prepared from hydrolyzed urine.

PMID- 14950184
TI  - Vitality of the aged.

PMID- 14950185
TI  - The use of the Selective Service College Qualification Test in the deferment of
      college students.

PMID- 14950186
TI  - Pollen and radiocarbon studies of Aleutian soil profiles.

PMID- 14950187
TI  - The effect of insulin coma on uropepsin excretion.

PMID- 14950188
TI  - Biosynthesis of the C14-labeled form of dextran.

PMID- 14950189
TI  - A dominant, sex-linked mutation in the house mouse.

PMID- 14950190
TI  - Uraninite from the Grey Dawn Mine, San Juan County, Utah.

PMID- 14950191
TI  - An effect of proteins and proteoses on the cellulase of Myrothecium verrucaria.

PMID- 14950192
TI  - Selective stimulation of color receptors with alternating currents.

PMID- 14950193
TI  - An improved lyophilizer.

PMID- 14950194
TI  - Sterilization of pyrogen-free injections in Fenwal bottles.

PMID- 14950195
TI  - Hotel Headquarters, Sixth St. Louis Meeting December 26-31, 1952.

PMID- 14950196
TI  - The constitution and functions of the United Kingdom Medical Research Council.

PMID- 14950197
TI  - Ability of mice of the genus Peromyscus to hear ultrasonic sounds.

PMID- 14950198
TI  - Infrared spectrophotometry as a means for identification of bacteria.

PMID- 14950199
TI  - Effect of penicillin on streptomycin-dependent variants in Escherichia coli
      populations.

PMID- 14950200
TI  - Cocontraction and reciprocal innervation in voluntary movement in man.

PMID- 14950201
TI  - Systematic status of the pure culture ciliate known as "Tetrahymena geleii" and
      "Glaucoma piriformis".

PMID- 14950202
TI  - Differential stability of various analogs of cobalamin to vitamin C.

PMID- 14950203
TI  - The metabolism of betaine and sodium formate by leukemic mice.

PMID- 14950204
TI  - Effect of excess dietary DL-methionine on liver and kidney catalase of rats.

PMID- 14950205
TI  - Inactivation of circulin by lipase.

PMID- 14950206
TI  - The action of metals on 1,4-dihalides and similar compounds.

PMID- 14950207
TI  - Three- and four-dimensional plotting.

PMID- 14950208
TI  - Periodic acid-Schiff reaction of the insect cuticle.

PMID- 14950209
TI  - Human hemoglobin.

PMID- 14950210
TI  - The chemical approach to the control of tuberculosis.

PMID- 14950211
TI  - Low energy counting with a new liquid scintillation solute.

PMID- 14950212
TI  - Body build and body composition.

PMID- 14950213
TI  - Specific volumes of proteins and the relationship to their amino acid contents.

PMID- 14950214
TI  - A note on the phosphorescence of proteins.

PMID- 14950215
TI  - The presence of toxins other than DDT in the blood of DDT-poisoned roaches.

PMID- 14950216
TI  - Differentiation between circulins A and B and polymyxins A and E by paper
      chromatography.

PMID- 14950217
TI  - Colloidal graphite in the preparation of samples for gas-flow counting.

PMID- 14950218
TI  - A method for quantitative evaluation of the effects of ionizing radiations on
      growth of adenocarcinoma in vivo.

PMID- 14950219
TI  - The effect of anesthesia upon adrenergic blockade.

PMID- 14950220
TI  - Use of sodium metabisulfite as a preservative for grass silage.

PMID- 14950221
TI  - The evidence for mitotic spindles in bacteria.

PMID- 14950222
TI  - Experimental pharmacology and measurement of the subjective response.

PMID- 14950223
TI  - Some pharmacologic characteristics of isonicotinyl hydrazide (Pyricidin); a new
      antituberculosis drug.

PMID- 14950224
TI  - Absorption of nutrients by stems and branches of woody plants.

PMID- 14950225
TI  - The activity of a-Armylase as determined by adsorption indicators.

PMID- 14950226
TI  - Systemic stress as an inhibitor of experimental tumors in Swiss mice.

PMID- 14950227
TI  - A "Purkinje shift" in insect vision.

PMID- 14950228
TI  - The protective effect of glutathione against radiation-induced chromosome
      aberrations.

PMID- 14950229
TI  - Absorption spectra and isomerization of the chlorophylis.

PMID- 14950230
TI  - Equilibria between species of chlorophylis in solution.

PMID- 14950231
TI  - CULTURE collections of microorganisms.

PMID- 14950233
TI  - [Investigations on superfetation of the mouse].

PMID- 14950232
TI  - [Tomography in retropneumoperitoneum].

PMID- 14950234
TI  - [Symptoms, pathophysiology and therapy of delirium tremens].

PMID- 14950235
TI  - [Pharmacology of the ACTH preparation Cibacthen].

PMID- 14950236
TI  - [Study of biochemical and clinical effects of a new ACTH preparation].

PMID- 14950237
TI  - [Man and technique in modern medicine].

PMID- 14950238
TI  - [Therapy of sigmoiditis diverticulosa].

PMID- 14950239
TI  - [Tissue iron in unexplained death].

PMID- 14950240
TI  - [Differential diagnosis and therapy of hypercalcuria and nephrolithias].

PMID- 14950241
TI  - [Effects of PAS on laryngeal, bronchial and intestinal complications of pulmonary
      tuberculosis].

PMID- 14950242
TI  - [Surgical therapy of tuberculosis of lymph nodes of the neck].

PMID- 14950243
TI  - [Therapy of tuberculosis of the lymph nodes of the neck with special
      consideration of the value of tonsillectomy].

PMID- 14950244
TI  - [Effects of chaulmoogra oil alone and in combination with PAS of TB I on
      experimental tuberculosis of mice].

PMID- 14950245
TI  - [Bilirubinemia and rheumatism; dangers of ACTH and cortisone].

PMID- 14950246
TI  - [Importance of contact in clinical-psychiatric therapy].

PMID- 14950247
TI  - [Method of determination of vitamin A in blood].

PMID- 14950248
TI  - [Therapy of adrenal cortical insufficiency].

PMID- 14950249
TI  - [Plate-like atelectasis in pleuritis exsudativa; etiology].

PMID- 14950250
TI  - [Production of resistance of m. tuberculosis against rimiform in vitro].

PMID- 14950251
TI  - [Observation of resistance of m. tuberculosis against rimiform in a patient
      treated with this drug; preliminary communication].

PMID- 14950252
TI  - [Anaphylaxis and general anesthesia].

PMID- 14950254
TI  - [Swiss Association for Dermatology and Venereology].

PMID- 14950253
TI  - Sickle cell anemia in Greece.

PMID- 14950255
TI  - [Influenza vaccination; experiences with vaccination of the personnel of the
      Bueger hospital in Basel, Switzerland 1951].

PMID- 14950256
TI  - [Nocturnal acid secretion in persons with normal and sick stomach].

PMID- 14950257
TI  - [Connection between somatic and psychic features of children].

PMID- 14950258
TI  - [Critique of the article: ultrasonics and central nervous system by H. Heyck].

PMID- 14950259
TI  - [Review of fifty years of American physiology].

PMID- 14950260
TI  - [Whooping cough].

PMID- 14950261
TI  - [Pneumopertussis].

PMID- 14950262
TI  - [Histopathology of the lung in whooping cough].

PMID- 14950263
TI  - [Modern treatment of whooping cough].

PMID- 14950265
TI  - [Classification of hemorrhagic diseases].

PMID- 14950264
TI  - [Some wetting agents and their application in gastroenterology].

PMID- 14950266
TI  - [Treatment of hemophilia by injections of plasma].

PMID- 14950267
TI  - [Neurological forms of infectious mononucleosis].

PMID- 14950268
TI  - [Hypertension in pregnancy of women previously maintained on deficiency diet].

PMID- 14950269
TI  - [Constitutional androgynism].

PMID- 14950270
TI  - [A new treatment of menopause: polysteroid hormone implantation].

PMID- 14950271
TI  - [Mechanism and possible treatment of staphylococcal bulla of the lungs].

PMID- 14950272
TI  - [Hypothyroidism secondary to pituitary insufficiency; Simmonds-Sheehan syndrome].

PMID- 14950273
TI  - [Placental blood with addition of alcohol employed as a therapeutic for the first
      time in Poland].

PMID- 14950274
TI  - [Rubber dermatitis].

PMID- 14950275
TI  - [New treatment of Basedow's disease].

PMID- 14950276
TI  - [Atypical pneumonia].

PMID- 14950277
TI  - [The discovery of human races].

PMID- 14950278
TI  - [Race and thermal regulation].

PMID- 14950279
TI  - [Race and nutrition].

PMID- 14950280
TI  - [Race and the notion of terrain].

PMID- 14950281
TI  - [Racial behavior differences in regard to parasitoses].

PMID- 14950282
TI  - [Distribution of the Rh factor in the human races].

PMID- 14950283
TI  - [Experimental and clinical study of therapeutic activity of maleylsulfathiazol].

PMID- 14950284
TI  - [Effect of his birth rank and the age of his procreators on physio-pathological
      character of the child].

PMID- 14950285
TI  - [Neurological and psychiatric disorders observed in the left-handed; diphasia;
      dipraxia and diphrenia].

PMID- 14950286
TI  - [Simulated diseases in malingerens (observed in military hospitals)].

PMID- 14950287
TI  - [Nutrition and ovoimplantation].

PMID- 14950288
TI  - [Physiology of the parotid].

PMID- 14950289
TI  - [Vascular cerebral malformations].

PMID- 14950290
TI  - [Clinical aspects of immunohematology; diseases of auto-aggression].

PMID- 14950291
TI  - [Acquired hemolytic anemia in adult with atrophic cirrhosis, complex nervous
      syndrome and Gougerot-Sjogren syndrome].

PMID- 14950292
TI  - [Hemolytic hypersplenic anemia].

PMID- 14950293
TI  - [Hemolysins in hemolytic anemia and hemoglobinuria].

PMID- 14950294
TI  - [Percutaneous penetration of sex hormones, value in detection of occupational
      diseases].

PMID- 14950295
TI  - [Anthropometric aspects of obesity].

PMID- 14950296
TI  - [Allergic syndromes and hormonal states; therapeutic deductions].

PMID- 14950297
TI  - [Surgery of aplasia of the ear].

PMID- 14950298
TI  - [Surgical deductions drawn from the study of 54 anatomical specimens of tetralogy
      of Fallot].

PMID- 14950299
TI  - [Scientific method in general medicine, especially in constitutional medicine].

PMID- 14950300
TI  - [Major role of heredity in endocrine and nutritional disorders].

PMID- 14950301
TI  - [Phenomena of progression and regression in phylogenic evolution of hereditary
      endocrinopaties].

PMID- 14950302
TI  - [Cerebral disorders secondary to hypoparathyroidism].

PMID- 14950303
TI  - [Abnormalities of psychic development and encephalogram in hypogonadism in
      adolescent; effect of testosterone].

PMID- 14950304
TI  - [Different anatomo-clinical types of post-emotional thyreoses].

PMID- 14950305
TI  - [In memoriam professor Levy-Valensi, secretary general of la Semaine des Hopitaux
      (1879-1943). A pilgrimage to Auschwitz].

PMID- 14950306
TI  - [Tracheo-bronchial foreign bodies].

PMID- 14950307
TI  - [Pituitary and cortical regulation for hepatic glycogenesis].

PMID- 14950308
TI  - [Clinical exploration of hepatic glycogenesis; glycogenic load and cortisone].

PMID- 14950309
TI  - [Treatment of obstinate cardiac insufficiencies].

PMID- 14950310
TI  - [Accidents in transfusion].

PMID- 14950311
TI  - [Potassium changes in some digestive disorders].

PMID- 14950312
TI  - [Remote sequelae of dolicho and megacolon].

PMID- 14950313
TI  - [State action on alcoholism].

PMID- 14950314
TI  - [Investigations on concentration of terramycin in blood in children].

PMID- 14950315
TI  - [Terramycin in pediatrics].

PMID- 14950316
TI  - [Potentiation and retardation of penicillin excretion with methylene blue].

PMID- 14950317
TI  - [Effect of dicumarol in standard doses on prolonged sub-febrile temperature].

PMID- 14950318
TI  - [Now concept on physiopathology of nerve fibers].

PMID- 14950319
TI  - [Myasthenia gravis; therapy].

PMID- 14950320
TI  - [Seminar on pathology, clinical medicine and surgical technique; benign tumor of
      the supraspinous fossa].

PMID- 14950321
TI  - [Seminar on pathology, clinical medicine and surgical technique; spring finger].

PMID- 14950322
TI  - [Physical considerations on electroencephalography in humans].

PMID- 14950323
TI  - [Technic of epidemiological investigation].

PMID- 14950324
TI  - [Certain clinical properties of obstetric shock and its diagnostic and
      therapeutic value].

PMID- 14950325
TI  - [Curare and histamine].

PMID- 14950326
TI  - [De Takata's reaction as a test in hepatic insufficiency].

PMID- 14950327
TI  - [Granuloma annulare; therapy].

PMID- 14950328
TI  - [Closing of the duodenum in gastrectomy; technic used and variations].

PMID- 14950329
TI  - [Neurogenic hypoglycemia].

PMID- 14950330
TI  - [Dehiscent placenta].

PMID- 14950331
TI  - [Affectivity in school age; investigation and reeducation].

PMID- 14950332
TI  - [Treatment of ulcerative colitis].

PMID- 14950333
TI  - [Results of streptomycin therapy of tuberculosis].

PMID- 14950334
TI  - [Cardiac vitamin B12 deficiency; preliminary communication].

PMID- 14950335
TI  - [Lobstein's disease].

PMID- 14950336
TI  - [Industrial hygiene; education].

PMID- 14950337
TI  - ANNUAL conference at Pittsburgh.

PMID- 14950338
TI  - EXPERTS condemn night-driving lens.

PMID- 14950339
TI  - ACTH and cortisone in treating eye conditions.

PMID- 14950340
TI  - Oakland's sight conservation program.

PMID- 14950341
TI  - Research program of the National Society.

PMID- 14950342
TI  - Diabetic eye conditions.

PMID- 14950343
TI  - How the industrial medical department functions in the vision program.

PMID- 14950344
TI  - [Clinical and psychopathological aspects of internal zoopathy delirium].

PMID- 14950345
TI  - [Safety needle for puncture of the cisterna magna].

PMID- 14950346
TI  - [Fibrinolytic activity of the blood in focal cerebral vascular lesions].

PMID- 14950347
TI  - [Clinical and anatomical considerations on vascular tumors of the vertebral
      canal].

PMID- 14950348
TI  - [Hydrops of the cavum septi pelludiei communicating with the basal cisternae].

PMID- 14950349
TI  - [Extensive thrombotic aneurysm of the right sylvian artery with endoventricular
      development].

PMID- 14950350
TI  - [Neurovegetative disorders in endocranial expansive lesions; thermoregulation
      disorders of sleep, of the ocular apparatus, and of the cardiovascular
      apparatus].

PMID- 14950351
TI  - [Sanatorium to be converted to rheumatic disease hospital].

PMID- 14950352
TI  - [Specific dyslexia].

PMID- 14950353
TI  - [The poliomyelitis epidemic of 1951].

PMID- 14950354
TI  - [The problem of school failures].

PMID- 14950355
TI  - [Quackery in Sweden; comments and date with reference to current discussion].

PMID- 14950357
TI  - [Not Available].

PMID- 14950356
TI  - [The treatment of bulbar conjunctivitis and keratoconjunctivitis].

PMID- 14950358
TI  - Confluent and reticular papillomatosis of the skin (Gougerot-Carteaud).

PMID- 14950359
TI  - Intestinal parasites in the Natal Bantu.

PMID- 14950361
TI  - The management of intussusception.

PMID- 14950360
TI  - The effect of bacteriophage on the respiration of E. coli and PS aeruginosa.

PMID- 14950362
TI  - Flies visiting human faces and carcasses in Johannesburg, Transvaal.

PMID- 14950363
TI  - Van Riebeeck's youth, family and medical training.

PMID- 14950364
TI  - VAN Riebeeck tercentenary.

PMID- 14950365
TI  - ARCHIVES for a history of medicine in South Africa; Van Riebeeckana and related
      matters.

PMID- 14950366
TI  - The history of scurvy.

PMID- 14950367
TI  - Benign ulcers on the greater curvature of the stomach.

PMID- 14950368
TI  - FUMAGILLIN: A new ameobacidal antibiotic.

PMID- 14950369
TI  - [Rudimentary occipital arm; unusual congenital abnormality].

PMID- 14950370
TI  - Osteitis tuberculosa multiplex cystoides.

PMID- 14950372
TI  - Neurofibromatosis report of a case.

PMID- 14950371
TI  - Bacterial sensitivity to anti-microbial agents; a warning against wanton waste of
      antibiotics and chemotherapeutic substances.

PMID- 14950373
TI  - Leukaemic tonsils.

PMID- 14950374
TI  - Prophylactic daily oral sulphadiazine therapy; its effect on circulating
      leucocytes.

PMID- 14950375
TI  - [Modern treatment of congenital megacolon (Hirschsprung's disease)].

PMID- 14950376
TI  - HAEMOPHILIA; modern concepts.

PMID- 14950378
TI  - Bacterial pneumonia.

PMID- 14950377
TI  - An analysis of 1617 consecutive births at St. Monica's Home, Cape Town.

PMID- 14950379
TI  - Jaw tumours III. Adamantinoma.

PMID- 14950380
TI  - The prothrombin level in patients on dicoumarol therapy; a simplified capillary
      technique.

PMID- 14950381
TI  - MALARIA survey of South West Africa.

PMID- 14950382
TI  - Floating gall stones report of a case.

PMID- 14950383
TI  - Bacterial pneumonia.

PMID- 14950384
TI  - Trachoma in the South African Bantu; a survey in Sekukuniland.

PMID- 14950385
TI  - Abscess tonsillectomy.

PMID- 14950386
TI  - Electroshock treatment of mental illness during pregnancy.

PMID- 14950387
TI  - Some observations on the melanosis of Riehl.

PMID- 14950388
TI  - SIR Bernard Spilsbury--a great man, a great witness or a great myth?

PMID- 14950389
TI  - Post-menopausal haematometra.

PMID- 14950390
TI  - Denture to dermoid.

PMID- 14950391
TI  - Puerperal sciatic palsy; traumatic neuritis of the puerperium.

PMID- 14950392
TI  - A case of yaws (framboesia tropica).

PMID- 14950393
TI  - Burns I. Recent advances in management.

PMID- 14950394
TI  - An unusual constriction ring of the uterus.

PMID- 14950395
TI  - The treatment of radium burn fistulae into bladder and rectum.

PMID- 14950396
TI  - Coarctation of the aorta with terminal haemopericardium.

PMID- 14950397
TI  - INFANTS and lead poisoning.

PMID- 14950398
TI  - The diagnosis of virus pneumonia.

PMID- 14950399
TI  - Burns II: Fluid therapy in relation to burn shock and healing.

PMID- 14950400
TI  - Situs inversus viscerum and bronchiectasis; report of a Bantu case associated
      with chronic cor pulmonale and renal anomalies.

PMID- 14950401
TI  - Coronary thrombosis with cardiac infarction; two probable cases in Africans.

PMID- 14950402
TI  - Cirrhosis of the liver its incidence in the Coloured people of the Cape
      Peninsula.

PMID- 14950403
TI  - MEMORIAM Dr. J. K. K. Stielau.

PMID- 14950405
TI  - The treatment of hypospadias.

PMID- 14950404
TI  - Traumatic haemothorax; vulgar errors in its treatment.

PMID- 14950406
TI  - Relapsing fever in South Africa; its control.

PMID- 14950407
TI  - Histoplasmosis in South Africa.

PMID- 14950408
TI  - Surgical emphysema in asthma.

PMID- 14950409
TI  - MEDICAL profession and problems of rehabilitation.

PMID- 14950410
TI  - Trauma in tonsillectomy; its prevention.

PMID- 14950411
TI  - Emergency hospitalization of young children; the psychological effects.

PMID- 14950412
TI  - Relapsing febrile nodular non-suppurative panniculitis; weber-christian disease:
      report of a case treated with ACTH.

PMID- 14950413
TI  - SENECIO alkaloids.

PMID- 14950414
TI  - Dermatoses from cosmetics.

PMID- 14950416
TI  - Malnutrition in the Native in the Transekei.

PMID- 14950415
TI  - Porphyria.

PMID- 14950417
TI  - SHORTAGE of nurses; first things first in a national emergency.

PMID- 14950418
TI  - Tracheotomy; a survey of 111 cases at Waterval Hospital 1945-1951.

PMID- 14950419
TI  - A rare anomaly of the nose in a bantu male.

PMID- 14950420
TI  - The shortage of nurses.

PMID- 14950421
TI  - Congenital duodenal stenosis and mongolism; report of a case.

PMID- 14950422
TI  - Intestinal bilharziasis in the Eastern Transvaal; a preliminary report.

PMID- 14950423
TI  - A background to industrial health.

PMID- 14950424
TI  - Cicatricial ectropion; its plastic repair.

PMID- 14950425
TI  - Some observations on the practice of medicine. Installment I.

PMID- 14950426
TI  - Psychoanalysis in everyday life.

PMID- 14950427
TI  - General practice.

PMID- 14950428
TI  - Repair of cystocele and rectocele by a simpler method.

PMID- 14950429
TI  - Therapeutics.

PMID- 14950430
TI  - VULVOVAGINITIS.

PMID- 14950431
TI  - Fracture in the aged.

PMID- 14950432
TI  - Local anesthesia sufficient and best in most obstetrics.

PMID- 14950433
TI  - [Problems in the field of dermatology according to the Pavlovian physiologic
      therapy].

PMID- 14950434
TI  - [Etiology and lupus erythematosus].

PMID- 14950435
TI  - [Penicillin dermatitis].

PMID- 14950436
TI  - [Gummous thyroidit treated with penicillin].

PMID- 14950437
TI  - [Epidermophytosis of the smooth skin].

PMID- 14950438
TI  - [Causes of fatal outcome in acute appendicitis and methods of prevention].

PMID- 14950439
TI  - [Surgical treatment of gastric and duodenal ulcer].

PMID- 14950440
TI  - [Kidneys damage in rheumatoid arthritis].

PMID- 14950441
TI  - [Cerebrospinal hypertensive syndrome in hypertension].

PMID- 14950442
TI  - [Sleep therapy of certain forms of hyperkinesia].

PMID- 14950443
TI  - [Treatment of precancerous conditions of the cervix uteri].

PMID- 14950444
TI  - [Clinico-anatomical conferences; discussion on S. M. Pavlenko's article "Certain
      methods and forms of reorganization of medical science and practice"].

PMID- 14950445
TI  - [Sedimentation reaction on slide with universal antigen for serodiagnosis of
      syphilis].

PMID- 14950446
TI  - [Ultraviolet irradiation of the neck region in insomnia].

PMID- 14950447
TI  - [Organization of control of venereal diseases in rural areas].

PMID- 14950448
TI  - [Control of microsporia].

PMID- 14950449
TI  - [Role of general surgeon in control of osteoarticular tuberculosis].

PMID- 14950450
TI  - [Measures in prevention of cancer of the cervix uteri].

PMID- 14950451
TI  - [G. A. Sokol'skii and his comments on "Textbook on medical practice" by
      Gufeland].

PMID- 14950452
TI  - [Problem of surgical aid].

PMID- 14950453
TI  - [Intra-tracheal penicillin therapy of pulmonary suppurations].

PMID- 14950454
TI  - [Treatment of peritonitis by intra-peritoneal administration of penicillin].

PMID- 14950455
TI  - [Cutaneous hemangioma in children and its therapy].

PMID- 14950456
TI  - [Clinical aspects of malignant tumors of the duodenum].

PMID- 14950457
TI  - [Causes of late diagnosis of cancer of the large intestine].

PMID- 14950458
TI  - [Nature of the clinical course of cancer in young adults and children].

PMID- 14950459
TI  - [Exercise therapy in the treatment of injuries of tendons of the wrist and
      fingers].

PMID- 14950460
TI  - [Application of massage in hypertension].

PMID- 14950461
TI  - [Mediastinal dermoid cysts and teratomas].

PMID- 14950462
TI  - [Prevention of tenosynovitis stenosans of the wrist flexors].

PMID- 14950463
TI  - [Preparation of the apparatus for drip-transfusion of the blood and blood
      substitutes].

PMID- 14950464
TI  - [Clinical aspects and pathogenesis of phagedenic ulcer].

PMID- 14950465
TI  - [Diagnostic errors in bronchial foreign bodies].

PMID- 14950467
TI  - [Management of a case of gun-shot wound of the stomach].

PMID- 14950466
TI  - [Technic of sutures in anastomoses].

PMID- 14950468
TI  - [Hemostatic sponge from heterogeneous blood].

PMID- 14950469
TI  - [Treatment of angina pectoris by intravenous administration of novocaine].

PMID- 14950470
TI  - [Combined chemotherapy of headache].

PMID- 14950471
TI  - [Use of vitrenous body preparation in gynecology].

PMID- 14950472
TI  - [Treatment of vaginal trichomoniasis with osarsol with white clay].

PMID- 14950473
TI  - [Sanitary services in construction of the Volga-Don canal].

PMID- 14950474
TI  - [Results of the treatment of pulmonary tuberculosis in rural regional centers].

PMID- 14950475
TI  - [Ibn-Sina (Avicenna)--a great scientist and physician].

PMID- 14950477
TI  - [Menace of repeating past errors].

PMID- 14950476
TI  - [Nikolai Evgen'evich Vvedenskii].

PMID- 14950478
TI  - [Method of organization of dispensary services for the population].

PMID- 14950479
TI  - [Dispensaries for workers at the V. M. Molotov Gorkovskii Automobile Plant].

PMID- 14950480
TI  - [Certain problems in dispensary services].

PMID- 14950481
TI  - [Auto-control of work of the district physician].

PMID- 14950482
TI  - [Organization of activities of the medico-sanitary section].

PMID- 14950483
TI  - [Review of activities of the regional hospital].

PMID- 14950484
TI  - [Fulfillment of certain items in the order No 870 of the Ministry of Public
      Health of USSR].

PMID- 14950485
TI  - [History of Rumanian Russian medical relations].

PMID- 14950486
TI  - [Preventive medicine in works of S. G. Zybelin, 1735-1802].

PMID- 14950487
TI  - [Clarification in medical journals of problems concerning morbidity of the
      population].

PMID- 14950488
TI  - [Elder physician-organizer].

PMID- 14950489
TI  - [Clinical aspects and diagnosis of pancreatic carcinoma].

PMID- 14950490
TI  - [Successful surgical therapy of traumatic lesions of the ciliary body].

PMID- 14950491
TI  - [Leptospirosis sejroe in Serbia].

PMID- 14950493
TI  - [Open treatment of burns in early and late stages].

PMID- 14950492
TI  - [Gastric secretion and gastric changes in subacute bacterial endocarditis].

PMID- 14950494
TI  - [Application and value of anamnestic reaction in Rh negative women sensitized
      with Rh antigen].

PMID- 14950495
TI  - [Gyrate atrophy of the retina and the vascular tunic with juvenile hereditary
      degeneration of the macula].

PMID- 14950496
TI  - [Not Available].

PMID- 14950497
TI  - [Unusual case of rhinolite].

PMID- 14950498
TI  - [Case of abdominal pregnancy with macerated fetus complicated by ileus].

PMID- 14950499
TI  - [Unusual case of congenital brachydactylia].

PMID- 14950500
TI  - [Chronic ileus in pancreatic tumor].

PMID- 14950501
TI  - [Atrophic rhinitis in a 2-year-old child].

PMID- 14950502
TI  - [Study of men and nature of a 100 year old paper in Serbia].

PMID- 14950503
TI  - [Seminar on terminology in Beograd].

PMID- 14950504
TI  - [Surgery of rheumatic fever and cardiac diseases in Serbia in 1949].

PMID- 14950505
TI  - [Intraspinal therapy].

PMID- 14950506
TI  - [Conservative therapy of acute pancreatitis].

PMID- 14950507
TI  - [Contraindication for surgical therapy of cardiac concretion].

PMID- 14950509
TI  - [Positional variations of the duodenum].

PMID- 14950508
TI  - [Laboratory diagnosis of atypic virus pneumonia].

PMID- 14950510
TI  - [Selection of patients and method of ureterocolostomy].

PMID- 14950511
TI  - [Use of electromagnets in eye surgery].

PMID- 14950512
TI  - [Causes and prevention of cracked nipples in pregnancy].

PMID- 14950513
TI  - [Atmosphere during the day and during the night; its action on the biological
      rhythm].

PMID- 14950514
TI  - [Calcium therapy of psychomotor and neurovegetative excitability in septic and
      toxic infections].

PMID- 14950515
TI  - [Etiology, pathology, and diagnosis of hemochromatosis; case diagnosed by
      aspiration biopsy of the liver].

PMID- 14950516
TI  - [Case of subtotal resection of the penis].

PMID- 14950517
TI  - [Congenital diaphragmatic hernia with complete evisceration of the bowel].

PMID- 14950518
TI  - [Rupture of the upper gluteal artery following intramuscular injections and its
      therapy].

PMID- 14950519
TI  - [Unusual toxic effect of methylthiouracil with myxedematous changes of the
      heart].

PMID- 14950520
TI  - [Vasa Pelagic as the educator in the field of public health].

PMID- 14950521
TI  - [Not Available].

PMID- 14950522
TI  - [Not Available].

PMID- 14950523
TI  - [The female parodontium under the influence of sexual specific hormones].

PMID- 14950524
TI  - [Report on comparing tests to find suitable model-materials for the indirect
      hydrocolloid impression for inlays].

PMID- 14950525
TI  - [Studies on the structure of the dental enamel under strain and dystrophical
      conditions].

PMID- 14950526
TI  - [Studies on the possibility of objective age determination by measuring the ash
      content of the teeth].

PMID- 14950527
TI  - [The elasticity of the osseous parts of the mastication system].

PMID- 14950528
TI  - [Proof of the protective effect of neutral fluorines on the disintegration of the
      enamel by acids on dogs in vivo].

PMID- 14950529
TI  - [On the movements of the orthodontic arch in the homogenous medium].

PMID- 14950530
TI  - [Clinical picture of postlactal dental caries; a contribution to the pathogenesis
      of dental caries].

PMID- 14950531
TI  - [The palate relief as a diagnostic help in the anthropologic proof of paternity].

PMID- 14950532
TI  - [Development of physics and its influence on ideology].

PMID- 14950533
TI  - [New results of investigation on mutations].

PMID- 14950534
TI  - [Effectiveness of x-ray therapy in different forms of lymphogranulomatosis].

PMID- 14950535
TI  - [Destructive and regulative effects of roentgenotherapy reducing hemopoiesis,
      especially of the lymphatic system].

PMID- 14950536
TI  - [Hourly reaction of leucocytes].

PMID- 14950537
TI  - [Experimental investigations on the motor function of irradiated small
      intestines].

PMID- 14950538
TI  - [Application of radioactive isotopes, especially of the natural radium isotope
      thorium x in clinical medicine].

PMID- 14950539
TI  - [Results of intravenous therapy with thorium x in spondylarthritis ancylopoetica
      (morbus Bechterew)].

PMID- 14950540
TI  - [Influence of different methods of therapy on carcinoma of breast].

PMID- 14950541
TI  - [Critical comments on measuring of dosage in roentgenotherapy, especially in
      carcinoma of breast].

PMID- 14950542
TI  - [Influence on potassium and calcium concentrations in the blood serum by
      artificial ozonization of air in rooms].

PMID- 14950543
TI  - [Small transportable ray detectors with low voltage counting chamber].

PMID- 14950544
TI  - [Method to determine location of intrauterine radium applicators in situ].

PMID- 14950545
TI  - [Supplementary dispersion for small fields].

PMID- 14950546
TI  - [Best wave lengths in short wave therapy].

PMID- 14950547
TI  - [Effects of ultrasonics on different developmental stages of drosophila
      melanogaster].

PMID- 14950548
TI  - [Effects of ultrasonics on the development of the chick and the frog egg].

PMID- 14950549
TI  - [Effect of ultrasonics on the organism].

PMID- 14950550
TI  - [Effect of ultrasonics and heat on tissue metabolism].

PMID- 14950551
TI  - [Thermic and mechanic effects of ultrasonics on single cells; investigation of
      the effect on eosinophil leucocytes].

PMID- 14950552
TI  - [Effect of ultrasonics on the central nervous system; seen from the viewpoint of
      a sound theory of function of the central nervous system].

PMID- 14950553
TI  - [Ultrasonic therapy of scleroderma].

PMID- 14950554
TI  - [Effect of ultrasonics on Sudek's syndrome].

PMID- 14950555
TI  - [Effect of ultrasonics on bone marrow].

PMID- 14950556
TI  - [Effects of ultrasonics on the rabbit heart].

PMID- 14950557
TI  - [Morphological and functional investigations on the effect of ultrasonics on the
      guinea pig ovary].

PMID- 14950558
TI  - [Investigations on bacteria treated with ultrasonics; special consideration of
      cytological problems].

PMID- 14950560
TI  - [Medical and surgical treatment of renal tuberculosis].

PMID- 14950559
TI  - [Exanthema subitum].

PMID- 14950561
TI  - [Comparative study of normal and pathological variations of gamma globulins].

PMID- 14950562
TI  - [Dehydration in newborn infants].

PMID- 14950563
TI  - [Tropical diseases and the medical work of Dr. Albert Schweitzer].

PMID- 14950564
TI  - [Streptomycin resistance of tubercle bacilli].

PMID- 14950565
TI  - [Cure of asthma convulsivum with pneumogastric infiltrations].

PMID- 14950566
TI  - [Favorable effect of ACTH in asthma convulsivum].

PMID- 14950567
TI  - [Treatment of evaluative cardiac rheumatism with ACTH].

PMID- 14950568
TI  - [Local treatment of infectious otorrheas with terramycin and chloromycetin].

PMID- 14950569
TI  - [Surgical treatment of coarctation of the aorta; a case operated on with
      success].

PMID- 14950570
TI  - [Results of streptomycin therapy in twenty-two cases of tuberculous meningitis in
      an adult].

PMID- 14950571
TI  - [Success of terramycin therapy in a case of brucellosis in man].

PMID- 14950572
TI  - [Biochemistry of the thyroid gland and of the thyroid hormone].

PMID- 14950573
TI  - [Photopantomography; a projected plan for combining photoroentgenography and
      pantomography].

PMID- 14950574
TI  - [Line focus in pantomography].

PMID- 14950575
TI  - [The effect of ultrasonics on diffusion in the teeth].

PMID- 14950577
TI  - [Dental economics and working conditions].

PMID- 14950576
TI  - [Newer impression materials].

PMID- 14950578
TI  - [The use of ozone in the local treatment of caries, pulpitis and periapical
      osteitis].

PMID- 14950579
TI  - [The implant denture].

PMID- 14950580
TI  - [Complications of delivery and their prevention].

PMID- 14950581
TI  - [Visual standards for motor vehicle operation].

PMID- 14950582
TI  - [Clinical laboratory work from the chemist's viewpoint].

PMID- 14950583
TI  - Esophagitis after esophagogastric anastomosis.

PMID- 14950584
TI  - Benign stenosing esophagitis associated with vomiting and intubation.

PMID- 14950585
TI  - A study of intestinal intubation using a flexible stylet with controllable tip.

PMID- 14950586
TI  - Arteriovenous fistula of the lung treated by dissection and excision without
      pulmonary excision.

PMID- 14950587
TI  - The effect of pregnancy on the tensile strength of healing laparotomy wounds in
      rats.

PMID- 14950588
TI  - Acute progressive unrelenting renal failure; a manifestation of severe shock
      associated with upper and lower nephron nephrosis.

PMID- 14950589
TI  - Surgical applications of an intra-arterial transfusion apparatus.

PMID- 14950590
TI  - Experimental ascites; its production and control.

PMID- 14950591
TI  - The construction of fresh autogenous arterial grafts. I. Use of the splenic
      artery to bridge a gap in the aorta.

PMID- 14950592
TI  - The production of chronic gastric hypervagotonia.

PMID- 14950593
TI  - Gastrojejunal ulcer; a ten-year study.

PMID- 14950594
TI  - Postoperative pain; its use in the comparative evaluation of analgesics.

PMID- 14950595
TI  - Squamous-cell carcinoma of the ampulla of Vater.

PMID- 14950596
TI  - Femoral vein graft following bilateral internal jugular vein resection.

PMID- 14950597
TI  - Avulsion and embolization of a calcific arterial plaque; femoral embolectomy.

PMID- 14950598
TI  - Aneurysm of the left gastric artery; a case report.

PMID- 14950599
TI  - Fatal pulmonary air embolism following lysis of adhesions; a case report.

PMID- 14950600
TI  - Ganglion of the hip; case report.

PMID- 14950602
TI  - BARNEY Brooks; 1884-1952.

PMID- 14950601
TI  - Surgery of tumors and hyper-functioning states of the adrenal glands.

PMID- 14950603
TI  - A surgeon's reflections on medical education.

PMID- 14950604
TI  - Respiratory acidosis; its relationship to cardiac function and other physiologic
      mechanisms.

PMID- 14950605
TI  - Significance of pulmonary hypertension in constrictive pericarditis; a pre and
      postoperative study.

PMID- 14950606
TI  - Observations on the circulation in high spinal anesthesia.

PMID- 14950607
TI  - Some effects upon the liver of complete arterialization of its blood supply.

PMID- 14950608
TI  - The temporary use of polyethylene shunts in the resection and homologous graft
      replacement of the aortic arch in the dog.

PMID- 14950609
TI  - Early and late effects of vagotomy on gastric secretions and motility.

PMID- 14950610
TI  - The significance of the sympathetic nervous system in acute cholecystitis.

PMID- 14950611
TI  - Arteriovenous fistulas and arterial aneurysms; the repair of major arteries
      injured in warfare, and the treatment of an arterial aneurysm with a vein graft
      inlay.

PMID- 14950612
TI  - Thromboendarterectomy for arteriosclerotic thrombosis of major arteries.

PMID- 14950613
TI  - Autotransplantation of thyroid tissue in the treatment of lingual thyroid.

PMID- 14950614
TI  - The retention of certain plasma volume expanders within the circulation of human
      subjects following a 1,000 cubic centimeter hemorrhage; a preliminary report.

PMID- 14950615
TI  - The danger of administering parenteral fluids by hypodermoclysis.

PMID- 14950616
TI  - Blood viscosity and the whole blood therapy of burns.

PMID- 14950617
TI  - Studies in cortisone; II. Metabolism in cortisone poisoning; effect of cortisone
      on tissue culture of fibroblasts.

PMID- 14950618
TI  - The effect of health insurance programs on residency training in surgery; the
      report of the committee on graduate training in surgery of the Society of
      University Surgeons.

PMID- 14950619
TI  - Extensive small bowel resection in young dogs; its effect on growth and
      development; an experimental study.

PMID- 14950620
TI  - Congenital malformations of the rectum and anus; I. Clinical features and
      surgical management in 120 cases.

PMID- 14950621
TI  - A new concept of the pathology of megaloureters.

PMID- 14950622
TI  - Functional results of small intestinal segments as bladder substitutes following
      pelvic evisceration; a progress report.

PMID- 14950623
TI  - Studies on the regeneration of gastric mucosa in the experimental animal.

PMID- 14950624
TI  - Gastrointestinal hemorrhage and ulceration associated with intracranial lesions;
      a clinical and experimental study.

PMID- 14950625
TI  - A critical evaluation of the Billroth I gastric resection.

PMID- 14950626
TI  - The treatment of peptic ulceration by extensive partial gastrectomy with
      gastroduodenostomy; a preliminary report.

PMID- 14950627
TI  - Halsted and the Society of University Surgeons.

PMID- 14950628
TI  - MEETING of the Society of University Surgeons Feb. 7-9, 1952, Baltimore, Md.

PMID- 14950629
TI  - Further observations on total body water. I. Normal values throughout the life
      span.

PMID- 14950630
TI  - Capillary fragility and menstruation.

PMID- 14950631
TI  - The treatment of complete unilateral harelips.

PMID- 14950632
TI  - Advantages of a stab wound ileostomy.

PMID- 14950633
TI  - Hemangiomas; treatment and repair of defects; report of minimal radiation dosage
      and of multiple suture procedure.

PMID- 14950634
TI  - The posterolateral approach in the surgical management of basilar neck,
      intertrochanteric and subtrochanteric fractures of the femur; a report of its use
      in 36 acute fractures.

PMID- 14950635
TI  - Primary carcinoma of the vagina.

PMID- 14950636
TI  - The management of acute cholecystitis.

PMID- 14950637
TI  - Intralaryngeal arytenoidectomy in bilateral abductor vocal cord paralysis.

PMID- 14950638
TI  - Cervical and intracranial intra-arterial pressures with and without vascular
      occlusion.

PMID- 14950639
TI  - Lymphosarcoma of the small intestine.

PMID- 14950640
TI  - A clinical and pathological study of the significance of malignant pyloric
      obstruction on postresection prognosis.

PMID- 14950641
TI  - Obstruction of the common bile duct; viscosity studies.

PMID- 14950642
TI  - Gastric carcinoma; a statistical study based on 344 cases from 1938 through 1947.

PMID- 14950643
TI  - The preservation of whole ACD blood collected, stored, and transfused in plastic
      equipment.

PMID- 14950644
TI  - The surgical risk of patients with heart disease.

PMID- 14950645
TI  - Scars remaining in atom bomb survivors; a four year follow-up study.

PMID- 14950646
TI  - The neuro-endocrine control of water and electrolyte excretion during surgical
      anesthesia.

PMID- 14950648
TI  - Management of ectopic pregnancy with massive intraperitoneal hemorrhage and
      shock.

PMID- 14950649
TI  - Further observations on total body water. II. Changes of body composition in
      disease.

PMID- 14950650
TI  - Technical considerations in resection of the head of the pancreas.

PMID- 14950651
TI  - Melanoma; a study of 222 cases.

PMID- 14950652
TI  - Partial hepatectomy; presentation of four cases and discussion of technique.

PMID- 14950653
TI  - Surgical treatment for idiopathic congenital megacolon (Hirschsprung's disease).

PMID- 14950654
TI  - The treatment of certain congenital malformations of the heart by the creation of
      pulmonic stenosis to reduce pulmonary hypertension and excessive pulmonary blood
      flow; a preliminary report.

PMID- 14950655
TI  - Carcinoma of the rectum in the female; effect of vaginal invasion on prognosis.

PMID- 14950656
TI  - A new approach for excision of carcinoma of the lower portion of the rectum and
      anal canal.

PMID- 14950657
TI  - Laboratory aids in surgical diagnosis.

PMID- 14950658
TI  - The value and significance of blood coagulation studies.

PMID- 14950659
TI  - Inefficient uterine action.

PMID- 14950660
TI  - Ascorbic acid in surgical patients with particular reference to their blood buffy
      layer. I. Survey of blood and tissues.

PMID- 14950661
TI  - Congenital malformations of the rectum and anus. II. Associated anomalies
      encountered in a series of 120 cases.

PMID- 14950662
TI  - Results of treatment of fractured mandibles by the Anderson splint.

PMID- 14950663
TI  - Congenital hernia of the diaphragm with special reference to right-sided hernia
      of the liver and intestines.

PMID- 14950664
TI  - The repair of diaphragmatic defects with cutis grafts; an experimental study.

PMID- 14950665
TI  - The need for adequate aftercare in complete rehabilitation of the disabled.

PMID- 14950666
TI  - Diagnosis, treatment, and prophylaxis of potassium deficiency in surgical
      patients; analysis of 404 cases.

PMID- 14950667
TI  - Hypotensive spinal anesthesia.

PMID- 14950668
TI  - The surgical treatment of varicose veins in pregnancy.

PMID- 14950669
TI  - Local recurrence following subtotal resection for gastric carcinoma.

PMID- 14950670
TI  - Spontaneous rupture of the esophagus; an experimental and clinical study.

PMID- 14950671
TI  - A phylogenetic study of recurrent anterior dislocation of the shoulder joint.

PMID- 14950672
TI  - The value of fresh frozen sections.

PMID- 14950673
TI  - Significance of the urine examination.

PMID- 14950674
TI  - B.J.D. Irwin, the fighting doctor; a biographical sketch.

PMID- 14950676
TI  - The surgical treatment of malignant exophthalmos.

PMID- 14950675
TI  - The role of the surgeon in thyrotoxicosis.

PMID- 14950677
TI  - Diagnosis and surgical treatment of pituitary tumors.

PMID- 14950678
TI  - The roentgenologic diagnosis of hyperparathyroidism.

PMID- 14950679
TI  - Surgical treatment of hyperparathyroidism.

PMID- 14950680
TI  - Pathologic diagnosis of primary hyperparathyroidism.

PMID- 14950681
TI  - Lesions of the adrenal glands.

PMID- 14950682
TI  - Pheochromocytoma from the laboratory standpoint.

PMID- 14950683
TI  - Islet-cell tumors of the pancreas.

PMID- 14950684
TI  - Treatment of testicular tumors.

PMID- 14950685
TI  - Independent carcinoma of breast and ovary.

PMID- 14950686
TI  - Roentgen therapy for ovarian dysfunction.

PMID- 14950687
TI  - The use and abuse of cortisone in surgery.

PMID- 14950688
TI  - Anesthesia for patients with certain diseases of the endocrine glands.

PMID- 14950689
TI  - Anatomy of the endocrine glands.

PMID- 14950690
TI  - Osseous Gaucher's disease; report of a case with pathologic fracture of the left
      humerus.

PMID- 14950691
TI  - The surgical treatment of chronic sinusitis.

PMID- 14950692
TI  - Benign and malignant tumors of the jaws.

PMID- 14950693
TI  - Cholelithiasis; familial predisposition.

PMID- 14950694
TI  - Diverticulitis versus carcinoma; report of two cases.

PMID- 14950695
TI  - Jejunal diverticulosis; a clinical study of 87 cases.

PMID- 14950696
TI  - Multiple primary carcinomas occurring in the stomach and colon.

PMID- 14950697
TI  - The surgical treatment of megacolon.

PMID- 14950698
TI  - Noninfectious trochanteric bursitis and peritendinitis.

PMID- 14950699
TI  - Muscle biopsy in the diagnosis of periarteritis nodosa; an evaluation.

PMID- 14950700
TI  - Limitations of histopathologic technics in the diagnosis of granulomas.

PMID- 14950701
TI  - Pilonidal disease.

PMID- 14950702
TI  - [Homogeneity of suspension salves].

PMID- 14950703
TI  - [Comments on measures to reduce prices of drugs. II].

PMID- 14950704
TI  - [Assay of the pharmacopeial bismuth compounds by means of ethylene
      diaminetetraacetic acid and eriochrome black T indicator].

PMID- 14950705
TI  - [Calcium aminosalicylate].

PMID- 14950706
TI  - [Mintacol solution].

PMID- 14950707
TI  - [Comments on the Danish drug industrial survey].

PMID- 14950709
TI  - [Small orders, high costs].

PMID- 14950708
TI  - [Disciplinary measures taken by the medical directorate].

PMID- 14950710
TI  - [Not Available].

PMID- 14950711
TI  - [Infusions].

PMID- 14950712
TI  - [Kungl. Farm. institutet; library list of periodicals].

PMID- 14950713
TI  - [Behavior disorders in children caused by slight brain lesions].

PMID- 14950714
TI  - [Transmission of tuberculosis in swimming pools].

PMID- 14950715
TI  - [Disinfectants containing chlorine and invert soaps; comments on their acute
      toxicity].

PMID- 14950716
TI  - [Hospital care of beggars suffering from narcomania].

PMID- 14950717
TI  - [Suggested labels for medical equipment and supplies].

PMID- 14950718
TI  - [Comments on the article, Qualification assessment in appointments of physicians
      for general hospitals, by J. Rudebeck].

PMID- 14950719
TI  - [Prevalent chronic and invalidating diseases].

PMID- 14950720
TI  - [Need for improvement in care of aged].

PMID- 14950721
TI  - [Results with a new preparation for hypertension].

PMID- 14950722
TI  - [Abdominal pains in spondylarthritis deformans; further studies].

PMID- 14950723
TI  - [Results of ambulant electroshock therapy].

PMID- 14950724
TI  - [Simple refractometer for determination of visual acuity].

PMID- 14950725
TI  - [Observations of the Lakarforbund on the proposed pharmacy control regulations].

PMID- 14950726
TI  - [Not Available].

PMID- 14950727
TI  - [Psychogenic nature of the CO syndrome].

PMID- 14950728
TI  - [Noradrenalin and heart infarct; preliminary report].

PMID- 14950729
TI  - [Bact. coli neapolitanum in a diarrhea epidemic in a children's home].

PMID- 14950730
TI  - [Bracht's technique in breech presentation].

PMID- 14950732
TI  - [Opinion of the medical directorate on the proposed pharmacy control
      regulations].

PMID- 14950731
TI  - [Evaluation of preparation for medical practice in general hospitals].

PMID- 14950733
TI  - [Review of the legislation concerning induced abortion in Sweden and other
      countries].

PMID- 14950734
TI  - [Arsenic and strychnine poisoning in children caused by tonic iron medicines].

PMID- 14950735
TI  - [Whooping cough vaccine].

PMID- 14950736
TI  - [Combined inoculation of infants].

PMID- 14950737
TI  - [Cerebral palsy; therapeutic considerations].

PMID- 14950738
TI  - [Administration of penicillin procaine tablets; reply to B. Hellstrom].

PMID- 14950739
TI  - [The value of clinical training; contribution to current discussion].

PMID- 14950740
TI  - [Statistical classification of disease, injuries and causes of death; opinions of
      the Lakarforbund on the proposed classification].

PMID- 14950741
TI  - [Proposed revision of pharmacy legislation; excerpts of comments].

PMID- 14950742
TI  - [Late sequels of thrombosis].

PMID- 14950743
TI  - [Use of blood donor center and transfusion service at a medium size rural general
      hospital].

PMID- 14950744
TI  - [Another case of ventricular septum perforation in heart infarct, diagnosed intra
      vitam].

PMID- 14950745
TI  - [Records of patients in open ward].

PMID- 14950746
TI  - [Evaluation of qualifications for general hospital physicians].

PMID- 14950747
TI  - [Ophthalmologic significance of Pavlov's theory].

PMID- 14950748
TI  - [The progress of ophthalmologic surgery].

PMID- 14950749
TI  - [Effect of the aqueous humor on bacterial phagocytosis of leukocytes].

PMID- 14950750
TI  - [Examination of cholinesterase activity of the serum and aqueous humor in
      glaucoma].

PMID- 14950751
TI  - [Effect of histamin on eye pressure].

PMID- 14950752
TI  - [Diagrams for the analysis and teaching of binocular and monocular motor
      function].

PMID- 14950753
TI  - [Ocular findings in a one-day old infant with cerebral hemorrhage].

PMID- 14950754
TI  - [Ophthalmologic aspects of hemorrhage in the newborn].

PMID- 14950755
TI  - [Molluscum contagiosum of the ocular conjunctiva].

PMID- 14950756
TI  - [The relation of hospitals to social security].

PMID- 14950757
TI  - [Considerations on the determination of hospital requirements; regional
      characteristics of the hospital potential].

PMID- 14950758
TI  - [A formula for post-cure].

PMID- 14950759
TI  - [Orientation of the battle against cancer in France].

PMID- 14950760
TI  - [Architecture of the hospital].

PMID- 14950761
TI  - [Research on new forms for hospital rooms].

PMID- 14950762
TI  - [The council of State and official financial irresponsibility].

PMID- 14950763
TI  - [Readaptation, third phase of medical care].

PMID- 14950764
TI  - [The development of the health services of a country].

PMID- 14950765
TI  - [Vladimir Nikotich Vinogradov; 70th anniversary of his birth and 45th anniversary
      of his medical, scientific, pedagogical and organizational activities].

PMID- 14950766
TI  - [Sleep therapy of hypertension].

PMID- 14950767
TI  - [Congestive hypertension and its pathogenesis].

PMID- 14950768
TI  - [Vestibular electrostimulation in various stages of hypertension].

PMID- 14950769
TI  - [Effect of nicotinic acid on blood pressure and on electrolyte content of the
      blood; in hypertension; mechanism of hypotensive action of nicotinic acid].

PMID- 14950770
TI  - [Vitamin A and carotene content in the blood in gastric and duodenal ulcer].

PMID- 14950771
TI  - [Role of chemotherapy in the treatment of hemolytic anemias].

PMID- 14950772
TI  - [Unipolar leads and their significance for the evaluation of Q and T waves in
      third lead].

PMID- 14950773
TI  - [Effect of iodine on lipoids in the blood in atherosclerosis].

PMID- 14950774
TI  - [Depressor effect of fish fat in experimental renal hypertension].

PMID- 14950775
TI  - [Clinical picture of dissecting aneurysm of the aorta].

PMID- 14950776
TI  - [Kitaev's reflex; compensation mechanism in mitral diseases].

PMID- 14950777
TI  - [Clinical aspects of disorders of neural regulation of respiration].

PMID- 14950778
TI  - [Certain problems of organization and condition of therapeutic aid in Moscow].

PMID- 14950779
TI  - [Case of osteopsathyrosis].

PMID- 14950780
TI  - [Project for medical treatment of hypertension according to data of the
      Therapeutic Institute of the Academy of Medicine of USSR].

PMID- 14950781
TI  - [Streptomycin therapy of meningitis tuberculosa and miliary tuberculosis].

PMID- 14950782
TI  - [Heteronymic hormone therapy in the management of prostate cancer].

PMID- 14950783
TI  - [Dust prevention & control].

PMID- 14950784
TI  - [Curarization by rectal route].

PMID- 14950785
TI  - [Study of some liver and blood tests during treatment with para-aminosalicylic
      acid].

PMID- 14950786
TI  - [Study of the absorption and tolerance of para-aminosalicylic acid administered
      in the form of a PAS-vitaminpectin complex].

PMID- 14950787
TI  - [Hypersensitivity to estrogens and its treatment].

PMID- 14950788
TI  - [Possible attenuation of the toxic effects of antabuse during its therapeutic
      use].

PMID- 14950789
TI  - [New amino alcoholated ether-oxides of morphine].

PMID- 14950790
TI  - [Study of the analgesic properties of some substitution derivatives of
      salicylamide].

PMID- 14950791
TI  - [The action of sodium citrate on arterial pressure when administered
      intravenously].

PMID- 14950792
TI  - [Technic for measuring the variations in the excitability of a motor nerve under
      the influence of local anesthetics].

PMID- 14950793
TI  - [Contribution to the pharmacodynamic study on certain alkylamines and arylamines.
      I. Octylamines].

PMID- 14950794
TI  - [Enzymatic treatment of protein and lipid disorders seen during nephritis
      (nephritis-nephrosis) and in Epstein's lipid nephrosis].

PMID- 14950795
TI  - [List of common names of patent medicines or medicines with registered trade
      marks].

PMID- 14950796
TI  - [First clinical data on the use of chemical mediators in situ (on the
      endometrium) in the treatment of disorders in hormonal sensibility].

PMID- 14950797
TI  - [Problems arising from the use of ACTH and cortisone in the treatment of
      Bouillaud's syndrome].

PMID- 14950798
TI  - [Treatment of oxyuriasis by diphenylacetate piperazine (D.P.P.)].

PMID- 14950799
TI  - [Scopolamine in parkinsonism].

PMID- 14950800
TI  - [Para-aminosalicylic acid in dermatology].

PMID- 14950801
TI  - [A case of gynecomastia appearing after administration of amphetamine].

PMID- 14950802
TI  - [Contribution to the study of the blood sugar lowering action of the guanidine
      nucleus. I. Streptomycin and dihydrostreptomycin].

PMID- 14950803
TI  - [Percutaneous absorption of the hydrocarbons of the benzene, cycloalkane,
      cycloalkene and terpene series].

PMID- 14950804
TI  - [The formation of ergot alkaloids in vitro and their chemical and pharmacological
      characteristics].

PMID- 14950806
TI  - [Radiological observations on pharmacodynamic experiments on the digestive tracts
      of various animals].

PMID- 14950805
TI  - [Circulation and elimination of organocupic compounds used in the treatment of
      inflammatory rheumatic diseases].

PMID- 14950807
TI  - [Pharmacodynamic actions of some aqueous solutions of plant oils].

PMID- 14950808
TI  - [Contribution to the study of ferrous tartrate].

PMID- 14950810
TI  - [Hyaluronidase; its physicochemical and biological properties].

PMID- 14950809
TI  - [Structure and properties of connective tissue].

PMID- 14950811
TI  - [Hyaluronidase and its therapeutic applications].

PMID- 14950812
TI  - [Hyaluronidase and fertilization].

PMID- 14950813
TI  - [Enzymes in human sterility].

PMID- 14950814
TI  - [Collagenases].

PMID- 14950815
TI  - [Streptokinase and fibrinolytic processes].

PMID- 14950816
TI  - [Therapeutic applications of streptokinase].

PMID- 14950817
TI  - [Hyaluronidase and postoperative hypodermoclysis in the adult].

PMID- 14950818
TI  - [Hyaluronidase in the rehydration of infants].

PMID- 14950819
TI  - [Study of certain substances with inhibit hyaluronidase].

PMID- 14950820
TI  - [First trials on the subcutaneous perfusion of oxytocics in conjunction with
      hyaluronidase].

PMID- 14950821
TI  - [Some results in the intrapleural use of streptokinase-streptodornase].

PMID- 14950822
TI  - [Ehlers-Danlos syndrome; report on three cases in a family strongly affected].

PMID- 14950823
TI  - [Mitral stenosis and lung tumor].

PMID- 14950824
TI  - [The sinobronchial syndrome; a Saturday demonstration].

PMID- 14950825
TI  - [Counseling of women requesting abortion in the maternal welfare center; first
      annual report].

PMID- 14950826
TI  - [Hospitals in northern Norway; comments].

PMID- 14950827
TI  - [Consumption of amphetamine preparations].

PMID- 14950828
TI  - [The 60th anniversary of institute for animal vaccine production].

PMID- 14950829
TI  - [New drugs for tuberculosis].

PMID- 14950830
TI  - [Antibacterial surface therapy with antiseptic salves].

PMID- 14950831
TI  - [Abuse of barbiturates].

PMID- 14950832
TI  - [Streptokinase and streptodornase].

PMID- 14950833
TI  - [Abuse of amphetamine and hypnotics; reply to Tor Christiansen].

PMID- 14950834
TI  - [Revised regulation of civil service salaries].

PMID- 14950835
TI  - [Report of the Rikstrygdeverk for 1950. C. Health insurance].

PMID- 14950836
TI  - [Developmental features of hospital function and administration].

PMID- 14950837
TI  - [The role of bronchoscopy in otolaryngology].

PMID- 14950838
TI  - [Prefrontal leukotomy; report on 143 cases].

PMID- 14950840
TI  - [Another case of retrolental fibrosis].

PMID- 14950839
TI  - [Congenital toxoplasmosis; the first case diagnosed in Norway].

PMID- 14950841
TI  - [Cases of hereditary cataract].

PMID- 14950842
TI  - [Allergy to heparin].

PMID- 14950843
TI  - [Allergy to heparin].

PMID- 14950844
TI  - [Perinatal mortality].

PMID- 14950845
TI  - [Addiction and habit formation in use of barbiturates].

PMID- 14950846
TI  - [Epidemic parotitis and meningitis].

PMID- 14950847
TI  - [Treatment of ulcerative colitis].

PMID- 14950848
TI  - [Developmental features of hospital function and administration].

PMID- 14950849
TI  - [Certain factors in the function and development of hospitals].

PMID- 14950850
TI  - Biochemical studies on carbohydrates. CLII. On substances (Pseudomucin) from cyst
      fluids obtained by Hammarsten's procedure of preparing pseudomucin.

PMID- 14950851
TI  - Identification by isolation of sugar components of a pseudomucin preparation.

PMID- 14950852
TI  - Studies on the chemotherapy of leprosy. I. Cepharanthin.

PMID- 14950853
TI  - Studies on the chemotherapy of leprosy. II. Koha.

PMID- 14950854
TI  - Studies on the antibiotic substances from actinomyces. VII. On the isolation of
      special anti-phlei factor from an actinomyces in a crystalline form.

PMID- 14950855
TI  - Genetical studies on skin diseases. VI. Ephelides inversa (Siemens).

PMID- 14950856
TI  - Genetical studies on skin diseases. VII. Dyschromatosis universalis hereditaria
      in 5 generations.

PMID- 14950857
TI  - Studies on the temperature of the gastrointestinal tract. III. Effects of cooling
      and warming the epigastrium on the intragastric temperature.

PMID- 14950858
TI  - Studies on the defense mechanism of the body and neurohumoral regulation. I. On
      the neurohumoral influence upon the phagocytic function of the white blood cell.

PMID- 14950859
TI  - Studies on the defense mechanism of the body and the neurohumoral regulation. II.
      On the role of N. splanchnicus and adrenal gland upon the antibody mobilization.

PMID- 14950860
TI  - Studies on brain stem (I). On the course and connections of the intrapontine
      facial nerve in human adult.

PMID- 14950861
TI  - [Galli-Mainini biological reaction].

PMID- 14950862
TI  - [Artificial fertilization].

PMID- 14950863
TI  - [Contrast microscopy of vaginal secretions].

PMID- 14950864
TI  - [Vaginal fibromyoma].

PMID- 14950865
TI  - [Giant atypic myoma].

PMID- 14950866
TI  - [Comments on a case of spontaneous delivery].

PMID- 14950867
TI  - [Case of lesions of the lumbosacral plexus following forceps delivery].

PMID- 14950868
TI  - [Study on the histology of gynecology in Spain].

PMID- 14950869
TI  - [Shortcoming of social security coverage of maternal welfare].

PMID- 14950870
TI  - [Giant fibroma of the broad ligament].

PMID- 14950871
TI  - [Skin and venereal diseases in pregnancy].

PMID- 14950872
TI  - [Menoconservative hysterectomy in uterine myoma].

PMID- 14950873
TI  - [Ultra-radical surgery in gynecology].

PMID- 14950874
TI  - [Radiotherapy of adnexitis in tuberculous peritonitis].

PMID- 14950875
TI  - [Problem of placentation].

PMID- 14950876
TI  - [Comments on 100 cases of genitourinary fistulas].

PMID- 14950877
TI  - [Surgical treatment of rectal tumors in the Surgical Clinic of Turin].

PMID- 14950878
TI  - [Experimental research on the results of total biliary derivation].

PMID- 14950879
TI  - [Streptococcic enzymes: streptodornase and streptokinase].

PMID- 14950880
TI  - [The problem of painful knees: isolated rupture of the meniscus; advantage of
      opaque arthrography].

PMID- 14950881
TI  - [The "authority-confidence complex" in medicine].

PMID- 14950882
TI  - [The pulse in surgical affections of the limbs].

PMID- 14950883
TI  - [Surgical indications in poliomyelitis].

PMID- 14950884
TI  - [Four years of conservative surgical treatment of arteritis of the limbs].

PMID- 14950885
TI  - [Post-operative therapy: azotemias].

PMID- 14950886
TI  - [Reestablishment of colon continuity after Hartmann operation].

PMID- 14950887
TI  - [Ligature of the vena cava inferior for repeated post-operative pulmonary
      embolisms].

PMID- 14950888
TI  - [Magnesium molybdate in psychic anorexias].

PMID- 14950889
TI  - [Ligature of the inferior vena cava in cardiac insufficiency].

PMID- 14950890
TI  - [New knowledge concerning diabetes mellitus].

PMID- 14950891
TI  - [Pulmonary localizations of Hodgkin's disease].

PMID- 14950892
TI  - [Mustard gas therapy of Hodgkin's disease].

PMID- 14950893
TI  - [Cortisone and ACTH therapy; principles of action].

PMID- 14950894
TI  - [Practical use of current synthetic anti-thyroid drugs].

PMID- 14950895
TI  - [Surgery in mitral valve stenosis; indications and contraindications].

PMID- 14950896
TI  - Prospects for prevention of influenza.

PMID- 14950897
TI  - Historical aspects of foreign bodies in the air and food passages.

PMID- 14950898
TI  - An analysis of the Richmond, Virginia, multiphasic health examination program.

PMID- 14950899
TI  - The history of circulatory research, leading to a wider view of the circulation.

PMID- 14950900
TI  - MEMOIR of Brooke Melancthon Anspach (1875-1951).

PMID- 14950902
TI  - Assessment of fitness for work in pulmonary tuberculosis.

PMID- 14950901
TI  - MEMOIR of Charles James Hatfield.

PMID- 14950903
TI  - The problem of self-discharges from sanatoria.

PMID- 14950904
TI  - The clinical evaluation of an artificial pneumothorax with special reference to
      early abandonment in favour of resection.

PMID- 14950905
TI  - Tuberculoma of the lung.

PMID- 14950906
TI  - [Aplastic anemia in miliary tuberculosis treated with streptomycin].

PMID- 14950907
TI  - [Partial nephrectomy in the treatment of renal tuberculosis].

PMID- 14950908
TI  - [Spontaneous pneumothorax and mechanism of shunt in pulmonary circulation].

PMID- 14950909
TI  - [Extensive intrabronchial lymphatic perforation in primary infection in a 16 year
      old patient].

PMID- 14950910
TI  - [Five years follow-up of a case of tuberculous rectal stenosis treated by
      radiations].

PMID- 14950911
TI  - [Indications and contra-indications for streptomycin therapy of pulmonary
      tuberculosis; with special reference to streptomycin resistance].

PMID- 14950912
TI  - [Epidemiology of tuberculosis in Leskovac; mortality in the last 50 years].

PMID- 14950913
TI  - [Report of activities of the National Institute for the Studies and Treatment of
      Tumors in Milano, 21 December, 1950-21 December, 1951].

PMID- 14950914
TI  - [Effect of polyphenoloxidase-catechol on Rous sarcoma in vitro].

PMID- 14950915
TI  - [Analysis of 221 cases of goiter surgery].

PMID- 14950916
TI  - [Testicular reticulohistiocytoma].

PMID- 14950917
TI  - [Lysozyme in neoplasms; blood lysozyme in neoplasms].

PMID- 14950918
TI  - [Lysozyme in neoplasms; tissue lysozyme in neoplasms].

PMID- 14950919
TI  - [Clinical evaluation of the activity of ethylenimine radical, supposed active
      group of nitrogen mustard].

PMID- 14950920
TI  - [Primary reticulosarcoma of the stomach; case reports].

PMID- 14950921
TI  - [Cancer of the larynx and its therapy; personal contribution].

PMID- 14950922
TI  - [Action of nucleic acid on cell multiplication and respiration. I. Development of
      Ehrlich's adenocarcinoma in mice treated with nucleic acids].

PMID- 14950923
TI  - [Comparative research on carbohydrate metabolism in neoplastic and normal
      homologous tissue].

PMID- 14950924
TI  - [Action of nucleic acids on cell multiplication. II. Action of nucleic acids on
      the development of fertilized eggs of the sea urchin].

PMID- 14950925
TI  - [Action of nucleic acids on cell multiplication. III. Action of nucleic acids on
      multiplication in vitro of fibroblasts in chick embryo].

PMID- 14950926
TI  - [Action of nucleic acids on cell multiplication and respiration. IV. Action of
      nucleic acids on respiration in neoplastic tissue].

PMID- 14950927
TI  - [Contribution to the study of reticulosarcoma of the stomach].

PMID- 14950928
TI  - [Racemose hamartoma of the bronchial artery].

PMID- 14950929
TI  - [Morphological modifications induced by a derivative of the hydrolysis of
      nitrogen mustard; beta, beta-dichloroethyl-beta"-ethanolamine hydrochlorate
      (Contardi) on pathologic tissue of man and animals].

PMID- 14950930
TI  - [Action of some hydrocarbons, carcinogenic and non-carcinogenic, on the activity
      of enzyme catalyzing processes of oxidation-reduction. I. Catalysis].

PMID- 14950931
TI  - [Action of nitrogen mustard on glycolysis of human epithelial neoplastic tissue].

PMID- 14950932
TI  - [Chemical and biological studies on an organ specific penicillin derivative
      leocillin].

PMID- 14950933
TI  - [Henoch's abdominal purpura].

PMID- 14950934
TI  - [Treatment of perforated peptic ulcer].

PMID- 14950935
TI  - [Hand crank for amputee's stocking].

PMID- 14950936
TI  - Nuclear class series.

PMID- 14950937
TI  - [Massive hyperlipemia in alcoholic intoxication].

PMID- 14950938
TI  - [Mercury poisoning].

PMID- 14950939
TI  - [Neurological review 1950].

PMID- 14950940
TI  - In memoriam August Jurisch.

PMID- 14950941
TI  - [The blood shortage].

PMID- 14950942
TI  - [Application of ether in the treatment of residual calculi of the bile duct].

PMID- 14950943
TI  - [Vertebral columns in rheumatology].

PMID- 14950944
TI  - [Ascorbic acid requirement for acclimatization to cold in monkey (rhesus)].

PMID- 14950945
TI  - [The so-called reactive psychoneuroses].

PMID- 14950946
TI  - [A case of tropical eosinophilia; diffuse pulmonary infiltration with
      eosinophilia; broncho-pulmonary syndrome with eosinophila].

PMID- 14950947
TI  - [Uterine inversion].

PMID- 14950948
TI  - [Treatment of arthritis].

PMID- 14950949
TI  - [Emergencies and anesthesia].

PMID- 14950950
TI  - [Clinical diagnosis of diabetes].

PMID- 14950951
TI  - [Treatment of cancer of the breast].

PMID- 14950952
TI  - [Health conditions in Montreal in 1951].

PMID- 14950953
TI  - [The heart, source of life, source of death].

PMID- 14950954
TI  - [Address at the opening session of the XXIst Congress of the Association of
      Canadian French Language Physicians].

PMID- 14950955
TI  - [Report of the editor in chief of the Bulletin of the Association of Canadian
      French Language Physicians, l'Union Medicale du Canada].

PMID- 14950956
TI  - [Address by Dr Paul Rene Archambault, the retiring president].

PMID- 14950957
TI  - [Address by Dr. Paul Robert, the incoming president].

PMID- 14950958
TI  - [Research on cancer etiology].

PMID- 14950959
TI  - [The Rh factor in obstetrics].

PMID- 14950960
TI  - [Uterine inversion (four cases)].

PMID- 14950961
TI  - [Histological prognosis of cancer of the breast].

PMID- 14950962
TI  - [Preliminary report of 25 cases of induced hypotension in thoracic surgery].

PMID- 14950963
TI  - [Surgery of coronary thrombosis].

PMID- 14950964
TI  - [Coronary thrombosis and surgery].

PMID- 14950965
TI  - [A case of coma with an etiology difficult to interpret].

PMID- 14950966
TI  - [Acute traumatic arterial thrombosis].

PMID- 14950967
TI  - [Hernioplasty with tantalum mesh].

PMID- 14950968
TI  - [A new hemostatic agent].

PMID- 14950969
TI  - [Prognosis and treatment of essential hypertension].

PMID- 14950970
TI  - [Radiopelvimetry].

PMID- 14950971
TI  - [Non-specific agglutinins as cause of errors in serodiagnosis of brucellosis].

PMID- 14950972
TI  - [The skin; in defense].

PMID- 14950973
TI  - [The last Surgeon of the King in Quebec, Antoine Briault].

PMID- 14950974
TI  - [Rural practice of medicine; its development].

PMID- 14950975
TI  - Postoperative response to small water loads. II. Operations on bone.

PMID- 14950976
TI  - Some notes on psychiatric referrals in the University of Michigan Hospital.

PMID- 14950977
TI  - NEW approved drugs: hexamethonium bromide; hydralazine hydrochloride.

PMID- 14950978
TI  - JOHN Willard Kemper, M.D.

PMID- 14950979
TI  - [Role of microorganisms in supplementary plant feeding].

PMID- 14950980
TI  - [Evolution of the live substance in the theory of origin of malignant tumors].

PMID- 14950981
TI  - [Microbiological methods in biochemical investigation].

PMID- 14950982
TI  - [Physiological significance of blood glycogen].

PMID- 14950983
TI  - [Forms of localization and quantities of hemoglobin in blood in various animals].

PMID- 14950984
TI  - [Auto-allergic reactions and their significance in pathology].

PMID- 14950985
TI  - [Mitosis and functional activity of the cell].

PMID- 14950986
TI  - [Works of P. P. Ivanov on the development of metamerism in protostomas and
      deuterostomas: 10th anniversary of his death].

PMID- 14950987
TI  - [Histological structures of the yolk sac in early pathological human embryo].

PMID- 14950988
TI  - [Abrupt hereditary changes in rabbits following cross breeding].

PMID- 14950989
TI  - [Hospital renovation and maintenance with cooperation of regular personnel of the
      establishment].

PMID- 14950990
TI  - [Hospital and home care combine to close the gap between the practice of medicine
      and the social sciences].

PMID- 14950991
TI  - [Visiting at the sick bed].

PMID- 14950992
TI  - [Large or small hospitals].

PMID- 14950993
TI  - [Basic principles for social service hospitals].

PMID- 14950994
TI  - [80th anniversary of Viktor Nikolaevich SHevkunenko].

PMID- 14950995
TI  - [Problem of surgical anesthesia and the theory on interoreceptors].

PMID- 14950996
TI  - [Therapeutic-prophylactic inhibition in pre- and postoperative periods].

PMID- 14950997
TI  - [Development of Pirogov's theory on osteoplasty in the Pirogov Surgical Society].

PMID- 14950998
TI  - [Application of metal appliances in the treatment of fractures of the
      extremities].

PMID- 14950999
TI  - [Formation of weight-bearing amputation stump].

PMID- 14951000
TI  - [Modification of surgical fixation of the spine].

PMID- 14951001
TI  - [Modified kineplasty of the forearm].

PMID- 14951002
TI  - [Surgical treatment of perilunar dislocations of the wrist].

PMID- 14951003
TI  - [Osteoplastic fixation of the scapula in paralysis of its muscles].

PMID- 14951004
TI  - [Remote results of conservative treatment of gun-shot wounds of the hip joint].

PMID- 14951005
TI  - [Method of exarticulation of the hip].

PMID- 14951006
TI  - [Amputation defects of the extremity in children].

PMID- 14951007
TI  - [Results of duodenojejunostomy in chronic duodenal stasis].

PMID- 14951008
TI  - [Physical and chemical changes of properties of certain plastics in adaptation to
      the living tissue in animals].

PMID- 14951009
TI  - [Life and activities of A. A. Kozlovskii; 10th anniversary of his death].

PMID- 14951010
TI  - [Schedule for students specializing in otolaryngology].

PMID- 14951011
TI  - [New form of preparation of otolaryngological cadres].

PMID- 14951012
TI  - [Diagnostic and prognostic significance of non-conditioned salivary-separating
      reflexes in neurinomas of the acoustic nerve].

PMID- 14951013
TI  - [Cortical regulation of vestibular reflexes in man].

PMID- 14951014
TI  - [Intralabyrinthine pressure and aural sensitivity thresholds to atmospheric
      pressure in pathological processes].

PMID- 14951015
TI  - [Morphological changes in the inner ear in aural circulatory disorders].

PMID- 14951016
TI  - [Improvement of diagnosis of cerebral abscesses with electroencephalography].

PMID- 14951017
TI  - [New tables of words for whispering test of hearing acuity].

PMID- 14951018
TI  - [Clinical peculiarities of traumatic suppurative otitis media].

PMID- 14951019
TI  - [Tissue therapy of hearing disorders].

PMID- 14951020
TI  - [Differential diagnosis of petrositis].

PMID- 14951021
TI  - [Nitrous oxide inhalation anesthesia in otolaryngology].

PMID- 14951022
TI  - [Pentoxy in the treatment of agranulocytosis].

PMID- 14951023
TI  - [Results of novocain iontophoresis in peritonsillar abscess instead of
      preliminary incision according to Letnik's method].

PMID- 14951024
TI  - [Treatment of angina phlegmonosa with penicillin-novocain block].

PMID- 14951025
TI  - [Anesthesia with the aid of novocain electrophoresis in tonsillectomy].

PMID- 14951026
TI  - [Lipase in chronic tonsillitis].

PMID- 14951027
TI  - [Symptoms of early stages of laryngeal tuberculosis].

PMID- 14951028
TI  - [Roentgenotherapy of disseminated laryngeal cancer].

PMID- 14951029
TI  - [Esophagotomy associated with sulfonamide-penicillin therapy in the treatment of
      foreign bodies of the esophagus].

PMID- 14951030
TI  - [Absorption capacity of the mucous membrane of the respiratory and
      gastrointestinal tracts].

PMID- 14951031
TI  - [Case of fibroma of the middle ear].

PMID- 14951032
TI  - [Unusual growth of aural polypi].

PMID- 14951033
TI  - [Three cases of osteomas of the mastoid process].

PMID- 14951034
TI  - [Angioma of the middle ear damaging a group of cerebro-cranial nerves].

PMID- 14951035
TI  - [Abscess of the left part of the temporal lobe spontaneously wandering through
      the external auditory canal].

PMID- 14951036
TI  - [Unusual case of epistaxis].

PMID- 14951037
TI  - [Case of large ethmoid cell osteoma].

PMID- 14951038
TI  - [Case of intranasal cerebral hernias].

PMID- 14951039
TI  - [Seven cases of laryngeal amyloidosis].

PMID- 14951040
TI  - [Bilateral paresis of the recurrent nerves].

PMID- 14951041
TI  - [Comparative evaluation of methods of tissue therapy in chronic suppurative
      otitis media].

PMID- 14951042
TI  - [Roentgenotherapy of furuncles of the external auditory canal].

PMID- 14951043
TI  - [Case of fibroma of the external ear].

PMID- 14951044
TI  - [Latent otitis-antritis in infants with nutritional disorders].

PMID- 14951045
TI  - [Case of otogenous thrombophlebitis of the cavernous sinus].

PMID- 14951046
TI  - [Effect of prolonged use of hearing aids on hearing].

PMID- 14951047
TI  - [Complex treatment of an acute angina catarrhalis with sodium salicylate with
      urotropin and autohemotherapy].

PMID- 14951048
TI  - [Four cases of allergic laryngeal edema].

PMID- 14951049
TI  - [Penicillin therapy of perichondritis and laryngeal edema].

PMID- 14951050
TI  - [Boris Sergeevich Preobrazhenskii; 60th anniversary of birth].

PMID- 14951051
TI  - [N. E. Vvedenskii and his theory].

PMID- 14951052
TI  - [Pavlovian theory on conditioned reflexes; 50th anniversary of conditioned
      reflexes].

PMID- 14951053
TI  - [Introduction of the Pavlovian physiological theory into scientific works and
      research of dermato-venereologic institutes].

PMID- 14951054
TI  - [Cutaneous pathology in psychical and neural diseases].

PMID- 14951055
TI  - [Results of the treatment of lupus tuberculosus with vitamin D2 associated with
      diathermocoagulation].

PMID- 14951057
TI  - [Comparative determination of sweating].

PMID- 14951056
TI  - [Results of the treatment of lupus erythematosus with PAS].

PMID- 14951058
TI  - [Phenomenon of repression of isomorphous reaction in psoriasis].

PMID- 14951059
TI  - [Effect of medicinal sleep on the course and the treatment of experimental
      syphilis].

PMID- 14951060
TI  - [Nartsissov's active modification in serodiagnosis of syphilis].

PMID- 14951061
TI  - [Endoscopic treatment of calculi of the ureter].

PMID- 14951062
TI  - [Acquired megaesophagus in fakirs].

PMID- 14951063
TI  - [New physiological procedure in function tests of the normal and pathological
      kidney].

PMID- 14951064
TI  - [Consent in surgery].

PMID- 14951065
TI  - [Prevention and therapy of whooping cough].

PMID- 14951066
TI  - [Hand and finger injuries].

PMID- 14951067
TI  - [New aspects of asthma].

PMID- 14951068
TI  - [Clinical aspects of latent adrenal insufficiency].

PMID- 14951069
TI  - [Therapeutic use of iron].

PMID- 14951070
TI  - [The institution of consent to surgery].

PMID- 14951071
TI  - [Rickets viewed by a pediatric surgeon].

PMID- 14951072
TI  - [Rickets and pseudo-syphilitic periostitis].

PMID- 14951073
TI  - [Some reflections on rickets].

PMID- 14951074
TI  - [Diagnosis, prophylaxis and treatment of rickets].

PMID- 14951075
TI  - [Rickets in early childhood].

PMID- 14951076
TI  - [The treatment of common acne and acne rosacea].

PMID- 14951077
TI  - [On the treatment of intestinal parasitosis].

PMID- 14951078
TI  - [The present treatment of breast cancer].

PMID- 14951079
TI  - [Symptom of muscle ache and fever and its treatment].

PMID- 14951080
TI  - [Beal Gustave].

PMID- 14951081
TI  - [Trial therapy with cobalt salt].

PMID- 14951082
TI  - [Alkaline phosphatase in the biology of osseous tissue; histochemical
      investigations].

PMID- 14951083
TI  - [Beginning of the inflammatory process in connective tissue].

PMID- 14951084
TI  - [Demonstration and cause of air embolism caused by aspiration from the lungs; an
      important form of arterial embolism of the major circulation].

PMID- 14951085
TI  - [Organ changes in chronic colchicine poisoning].

PMID- 14951086
TI  - [Increase of bronchogenic carcinoma in a postmortem statistics 1895-1950].

PMID- 14951087
TI  - [Granulomata of the gastrointestinal tract].

PMID- 14951088
TI  - [The light cells of the human endometrium].

PMID- 14951089
TI  - [Etiology of subendocardial bleeding].

PMID- 14951090
TI  - [Approach to postmortem examination in the change of times; a study in history of
      culture].

PMID- 14951091
TI  - [Diagnosis of uremia in the corpse. II. Ammonia content of the gastric mucosa of
      fresh resection preparations in the pyloric- and fundal region].

PMID- 14951092
TI  - [Cubitus valgus, a constitutional abnormality].

PMID- 14951093
TI  - [Pathology of the fetus and newborn children of diabetic mothers].

PMID- 14951094
TI  - [A rare clinical case of hypoprothrombinemia].

PMID- 14951095
TI  - [Histopathology & therapy of hyperthyroidism of wild rabbit caused by fright].

PMID- 14951096
TI  - [Rheumatism, allergic-hyperergic inflammation and adrenal glands].

PMID- 14951097
TI  - [Measurement of muscle fibers and nuclear changes in numeric hyperplasia of the
      myocardium].

PMID- 14951098
TI  - [Organ damages and body injuries by pressure effects of explosions].

PMID- 14951099
TI  - [Pathogenesis of hydropic cell changes in liver and kidney].

PMID- 14951100
TI  - [Eosinophilic granuloreticuloma].

PMID- 14951102
TI  - [Histogenesis of the tubercle in the chorio-allantois membrane of the chick
      embryo].

PMID- 14951101
TI  - [Cell metabolism in the spleen after sensitization].

PMID- 14951104
TI  - [Basic ideas in oncology].

PMID- 14951103
TI  - [Pathogenesis of the cystic fibrosis of the pancreas].

PMID- 14951105
TI  - [When Virchow was a young physician].

PMID- 14951106
TI  - [Argyrophile cells].

PMID- 14951107
TI  - [Transplantation of spleen tissue].

PMID- 14951108
TI  - [Lymphangiectasia pulmonum congenita].

PMID- 14951109
TI  - [Allergic-hyperergic inflammation and colloidal sulfur].

PMID- 14951110
TI  - [New formation of cartilage cells].

PMID- 14951111
TI  - Edema and lymphedema of the lower extremities.

PMID- 14951112
TI  - Subtypes of migraine.

PMID- 14951113
TI  - Steroid hormones and rheumatism; report of two cases of rheumatoid arthritis.

PMID- 14951114
TI  - Acute porphyria and one false initial diagnosis due to the previous taking of
      pyridium.

PMID- 14951115
TI  - How young am I?

PMID- 14951116
TI  - Gastric surgery in a small hospital.

PMID- 14951117
TI  - A review of present concepts on the autonomic control to the gastrointestinal
      viscera: clinical applications.

PMID- 14951118
TI  - SEMINOMA of the testicle.

PMID- 14951119
TI  - Basal cell epithelioma in childhood.

PMID- 14951120
TI  - Results of subtotal gastric resection for peptic ulcer.

PMID- 14951121
TI  - CLINICOPATHOLOGICAL reports; mucus-secreting adenocarcinoma of the lung with
      metastases to the regional lymph nodes, adrenals, spleen, and brain.

PMID- 14951122
TI  - Public health.

PMID- 14951123
TI  - The guidance clinic as a community resource.

PMID- 14951125
TI  - TRENDS in medical education.

PMID- 14951124
TI  - HENRY Rose Carter, C.E., M.D. 1852-1925.

PMID- 14951126
TI  - [Hunger edema (nutritional dystrophy)].

PMID- 14951127
TI  - [Organization of medical services in tank-units].

PMID- 14951128
TI  - [Epidemic of leptospirosis pomonain Pirot].

PMID- 14951129
TI  - [Water-borne epidemic of typhoid fever in Ulcinj in 1947 and 1950].

PMID- 14951130
TI  - [Chemical substances and drugs in preventive medicine].

PMID- 14951131
TI  - [Treatment of ocular tuberculosis with vitamin D2; preliminary report].

PMID- 14951132
TI  - [Data of the N. N. Burdenko Institute of the Academy of Medicine of USSR on
      surgical therapy of adenohypophyseal tumors].

PMID- 14951133
TI  - [Prolonged drainage of lateral ventricles of the brain].

PMID- 14951134
TI  - [Suture of the posterior cranial fossa].

PMID- 14951135
TI  - [Latent course and remission in tumors of the spinal cord].

PMID- 14951136
TI  - [Congenital intraspinal tubulodermoid].

PMID- 14951137
TI  - [Diagnostic peculiarities in static and motor ataxia in cerebral tumors].

PMID- 14951138
TI  - [Clinical course and surgical therapy of angioreticulomas].

PMID- 14951139
TI  - [Metastatic cerebral tumors in children].

PMID- 14951140
TI  - [Bioelectric characteristics of the muscles in man in neural regeneration
      following anastomosis].

PMID- 14951141
TI  - [25th Anniversary of activities of the Leningrad Neurosurgical Institute and its
      future tasks in organization of network of neurosurgical services in RSFSR].

PMID- 14951142
TI  - [5th Neurosurgical conference dedicated to the memory of Nikolai Nilovich
      Burdenko].

PMID- 14951143
TI  - The problem of prematurity from the point of view of the obstetrician.

PMID- 14951144
TI  - Prematurity from the standpoint of the pediatrician.

PMID- 14951145
TI  - Presidential address.

PMID- 14951146
TI  - Experiences with the Billroth I subtotal gastric resection.

PMID- 14951147
TI  - Acute pancreatitis; a discussion of some of the signs and symptoms.

PMID- 14951148
TI  - Erythroblastosis fetalis.

PMID- 14951149
TI  - The Golden Age of medicine.

PMID- 14951150
TI  - Uterine curettage.

PMID- 14951151
TI  - [The virus hepatitides and their therapy].

PMID- 14951152
TI  - [Abdomino-anal radical operation of the rectum carcinoma with preservation of
      continence].

PMID- 14951153
TI  - [Bleeding effect after sole progesterone therapy of secondary amenorrhea].

PMID- 14951154
TI  - [Determination of intensity of irritation in diagnosis of paralyses].

PMID- 14951155
TI  - [Aminopterin therapy of acute leukemias].

PMID- 14951156
TI  - [Observations in Q fever].

PMID- 14951157
TI  - [Modern therapy of otogenous meningitis].

PMID- 14951158
TI  - [Report from the international continuing education course of the Vienna Medical
      Academy for continuing medical education].

PMID- 14951159
TI  - [Scientific Medical Association of Innsbruck].

PMID- 14951160
TI  - [Evaluation of injuries and diseases of the eye].

PMID- 14951161
TI  - [Conservative therapy of electric injuries as the way of nature].

PMID- 14951162
TI  - [Histopathology of present forms of human encephalitis].

PMID- 14951163
TI  - [Abnormalities of the embryo with special consideration of toxoplasmosis].

PMID- 14951164
TI  - [Operative prophylaxis and therapy of scoliosis caused by poliomyelitis].

PMID- 14951165
TI  - [Vitamin C requirement in the menstrual cycle].

PMID- 14951166
TI  - [Report from the international continuing education course of the Vienna Medical
      Academy for continuing medical education].

PMID- 14951167
TI  - [Scientific Medical Society of Innsbruck].

PMID- 14951168
TI  - [Official protocol of the Society of Vienna Physicians].

PMID- 14951170
TI  - [Results of surgery of choledocholithiasis].

PMID- 14951169
TI  - [Modern theories on the location of antibody formation].

PMID- 14951171
TI  - [Simultaneous counting- and differentiation method of leucocytes as a method to
      determine the stress syndrome].

PMID- 14951172
TI  - [Therapy of epilepsy].

PMID- 14951173
TI  - [Lysotopia of Salmonella typhi and paratyphi B].

PMID- 14951174
TI  - [Vegetative therapy of the infantile eczema].

PMID- 14951175
TI  - [Report from the international continuing education course of the Vienna Medical
      Academy for continuing medical education].

PMID- 14951176
TI  - [Scientific Medical Society of Innsbruck].

PMID- 14951178
TI  - [Physicians' seminar evening of the Van-Swieten Society at the Villach Regional
      Hospital].

PMID- 14951177
TI  - [Physicians' seminar evening in Salzburg].

PMID- 14951179
TI  - [Official protocol of the Society of Vienna Physicians].

PMID- 14951180
TI  - [Diagnosis and therapy of atypical pneumonias and common cold].

PMID- 14951181
TI  - [Increase, not decrease of infantile mortality in the third month of life in
      Vienna 1948-1951].

PMID- 14951182
TI  - [Scar tissue formation after strumectomy].

PMID- 14951183
TI  - [Irradiation damage of the great vessels].

PMID- 14951184
TI  - [Combination therapy of cerebral convulsions with special consideration of
      epilepsy].

PMID- 14951185
TI  - [Professor Ernst Peter Pick].

PMID- 14951186
TI  - [NoAustrian Society for Physical Hygiene].

PMID- 14951187
TI  - [Pyocyaneus infection and its therapy].

PMID- 14951188
TI  - [Pyrogenic reactions after intravenous injection].

PMID- 14951189
TI  - [Intraarticular cortisone therapy].

PMID- 14951190
TI  - [Stability of serum colloids and reticuloendothelial system; demonstrated on the
      model of malignant post-war endocarditis].

PMID- 14951191
TI  - [Transient presence of a mitral opening sound in acute rheumatic carditis].

PMID- 14951192
TI  - [Unilateral kidney bleeding in hypoprothrombinemia].

PMID- 14951193
TI  - [Report from the international continuing education course of the Vienna Medical
      Academy for continuing medical education].

PMID- 14951194
TI  - [Tha Austria Chapter of the International College of Surgeons: Program of the
      III. Surgery Meeting in ViennaTha Austria Chapter of the International College of
      Surgeons: Program of the III. Surgery Meeting in Vienna].

PMID- 14951195
TI  - [Official protocol of the Society of Vienna Physicians].

PMID- 14951196
TI  - [Experimental basis of modern hearing theories].

PMID- 14951197
TI  - [Effects of ACTH and cortisone on the levulose metabolism].

PMID- 14951198
TI  - [Recidive after intestinal obstruction caused by biliary calculi].

PMID- 14951199
TI  - [Brother and sister infested with Cooley anemia; their parents showing symptoms
      of thalassemia minor].

PMID- 14951200
TI  - [Therapy of peripheral arterial embolism].

PMID- 14951201
TI  - [Report from the international continuing education course of the Vienna Medical
      Academy for continuing medical education].

PMID- 14951202
TI  - [Physicians' seminar evening in Salzburg].

PMID- 14951204
TI  - [Official protocol of the Society of Vienna Physicians].

PMID- 14951203
TI  - [Ophthalmology Society of Vienna].

PMID- 14951205
TI  - [Problems of mucopolysaccharides of the connective tissue, of the mucoid
      substances and their specific enzymes].

PMID- 14951206
TI  - [Function of mast cells].

PMID- 14951207
TI  - [The so-called icterus syphiliticus praecox].

PMID- 14951208
TI  - [Surgery of liver cirrhosis].

PMID- 14951209
TI  - [Incidence, peculiarities and prognosis in surgery of aged].

PMID- 14951210
TI  - [Report from the international continuing education course of the Vienna Medical
      Academy for continuing medical education].

PMID- 14951211
TI  - [Official protocol of the Society of Vienna Physicians].

PMID- 14951212
TI  - [Active immunisation with combined vaccines].

PMID- 14951213
TI  - [Effects of implantation of posterior pituitary tissue in a patient with diabetes
      inspidus; determination of hormones & clearance].

PMID- 14951214
TI  - [Acute thrombopenic purpura caused by antabuse therapy].

PMID- 14951215
TI  - [Clinical effects of a new analeptic drug in children].

PMID- 14951216
TI  - [History of the so-called prostate hypertrophy and carcinoma].

PMID- 14951217
TI  - [Appendicitis in aged].

PMID- 14951218
TI  - [Professor Dr. Franz Lucksch].

PMID- 14951219
TI  - [Fifth Meeting of the Austrian Radiography Society].

PMID- 14951220
TI  - [Official protocol of the Society of Vienna Physicians].

PMID- 14951221
TI  - [Modern hormone therapy of women].

PMID- 14951223
TI  - [Effects of low power roentgen rays in the electrodermatogram].

PMID- 14951222
TI  - [Investigations of fulminate, lethal pulmonary embolisms in the post mortem
      material of the years 1941-1951].

PMID- 14951224
TI  - [Acute problems and clinical application of heart sound registration].

PMID- 14951225
TI  - [Apparatus for formation of an antibiotic fibrin film].

PMID- 14951226
TI  - [Age-related hearing loss].

PMID- 14951227
TI  - [Senile deafness].

PMID- 14951228
TI  - [Comparative therapy of vaginal discharge].

PMID- 14951229
TI  - [Physiology of islet cells and pathogenesis of diabetic symptoms with comments on
      genesis of incretory glands].

PMID- 14951230
TI  - [The problem of Foehn and its correlation to the autonomic nervous system].

PMID- 14951231
TI  - [New results of surgery of hypertension].

PMID- 14951232
TI  - [Ependymomata of the spinal cord and the cauda equina].

PMID- 14951234
TI  - [Report from the international continuing education course of the Vienna Medical
      Academy for continuing medical education].

PMID- 14951233
TI  - [Osteoporosis and osteomalacia, two diseases of old age].

PMID- 14951235
TI  - [NoOfficial protocol of the Society of Vienna Physicians].

PMID- 14951236
TI  - [Systematic and etiological investigations of virus].

PMID- 14951237
TI  - [New research on the development of gonads in man].

PMID- 14951238
TI  - [A case of duplicity of the stomach].

PMID- 14951239
TI  - [Development of diagnosis].

PMID- 14951240
TI  - [Malnutrition of aged].

PMID- 14951241
TI  - [Report from the international continuing education course of the Vienna Medical
      Academy for continuing medical education].

PMID- 14951242
TI  - [Physicians' seminar evening in Salzburg].

PMID- 14951243
TI  - [Official protocol of the Society of Vienna Physicians].

PMID- 14951244
TI  - [A new lymphatic disease and a new virus; benign inoculation lymphoreticulosis].

PMID- 14951245
TI  - [Clinical and histological pictures as polarized effects of electric current].

PMID- 14951246
TI  - [Potassium in surgery].

PMID- 14951247
TI  - [Cystic fibrosis of pancreas in a 16 years old girl].

PMID- 14951248
TI  - [Effects of implantations of pineal tissue and pineal extracts of malignancies in
      man].

PMID- 14951249
TI  - [Psychohygiene of aged].

PMID- 14951250
TI  - [Official protocol of the Society of Vienna Physicians].

PMID- 14951251
TI  - [Old and new problems in anatomy].

PMID- 14951252
TI  - [Gangrene caused by venous thrombosis (phlegmasia careulea dolens].

PMID- 14951253
TI  - [Therapeutic use of iron].

PMID- 14951254
TI  - [Application of drugs by ultrasonics].

PMID- 14951255
TI  - [Therapy of Raynaud's disease].

PMID- 14951257
TI  - [Physicians' seminar evening in Salzburg].

PMID- 14951256
TI  - [Blood dyscrasias in old aged people].

PMID- 14951258
TI  - [Austrian Dermatology Society].

PMID- 14951259
TI  - [Critique of therapy of scolioses].

PMID- 14951260
TI  - [Epilepsy and choice of an organ; a remarkable case of epilepsy].

PMID- 14951261
TI  - [A case of congenital diverticulum of the stomach].

PMID- 14951262
TI  - [Long-lasting tetanic spasm during antirabietic therapy of men].

PMID- 14951263
TI  - [Influence of age factor on the course of infectious diseases].

PMID- 14951264
TI  - [Society for Physical Medicine and its border areas].

PMID- 14951265
TI  - [Modern therapy of osteoarticular tuberculosis].

PMID- 14951266
TI  - [Changes of the spinal disc and concussion of the brain, anamnesis, diagnosis,
      therapy and opinion].

PMID- 14951267
TI  - [On the 48-hour critical period in acute appendicitis].

PMID- 14951268
TI  - [Hormone therapy of cancer of the breast, indication and control].

PMID- 14951269
TI  - [Foreign bodies in the esophagus].

PMID- 14951270
TI  - [On cancer diagnostic].

PMID- 14951271
TI  - [Arrosion of the aorta caused by esophageal ulcer].

PMID- 14951272
TI  - [Survey for diptheria carriers of healthy and sick persons].

PMID- 14951273
TI  - [Early diagnosis of tubercular meningitis in infant].

PMID- 14951274
TI  - [The conservative therapy of gastroduodenal ulcers and its limitations].

PMID- 14951275
TI  - [Indication and results of splenectomy and its substitute operation].

PMID- 14951276
TI  - [Changes of the mucous membrane of the pars pylorica and of the pars superior
      duodeni in pernicious anemia].

PMID- 14951277
TI  - [Circumambulating (the various aspects of postoperative thrombosis and
      thromboembolism)].

PMID- 14951278
TI  - [Difficulties in early diagnosis of spinal tuberculosis in infancy].

PMID- 14951279
TI  - [Two contributions on the injuries of the pancreas and a suggestion for
      predigestion of food by duodenal juice of relatives in loss of the digestive
      gastric, liver and pancreas ferments].

PMID- 14951280
TI  - [The method of retrograde catheterization of the posttraumatic strictured
      urethra].

PMID- 14951281
TI  - [Epicondylitis of the humerus].

PMID- 14951282
TI  - [A case of trifid ureter].

PMID- 14951283
TI  - [On postoperative edema of the brain].

PMID- 14951284
TI  - [Permanent results with Whitehead's operation of hemorrhoids].

PMID- 14951285
TI  - [Therapy of osteoarticular tuberculosis according to Rollier's method].

PMID- 14951286
TI  - [On the operation of large median abdominal hernias].

PMID- 14951287
TI  - [Contribution of several rare cases in thoracic and heart surgery].

PMID- 14951288
TI  - [The arterial varicose ulcer and its therapy].

PMID- 14951289
TI  - [The danger of perforation in cholecystitis during the acute inflammatory and the
      interval period].

PMID- 14951290
TI  - [On the genesis of the so-called wandering gall-bladder, explained in a case of
      pedicle torsion].

PMID- 14951291
TI  - [The therapy of the phimosis'; postoperative therapy according to Forderl's
      method].

PMID- 14951292
TI  - [The significance of fluorine for the teeth].

PMID- 14951293
TI  - [The central metabolic reaction to the parenteral administration of amino acids].

PMID- 14951295
TI  - [A case of sinistro position of the colon].

PMID- 14951294
TI  - [Therapy of leucopenia and anemia in x-ray therapy of cancer with short-wave
      irradiation of the midbrain].

PMID- 14951296
TI  - [Metastatic brain tumors; evaluation of 97 cases].

PMID- 14951297
TI  - [Metabolism under the influence of the hormone organs and the other catalytic
      factors].

PMID- 14951298
TI  - [Postoperative pain prevention after tonsillectomy].

PMID- 14951299
TI  - [Cancer and virus].

PMID- 14951300
TI  - [Effects of tissue extracts on the function of the connective tissue (reticulo
      endothelial system].

PMID- 14951301
TI  - [Multiple space-taking processes in cerebral roentgenography, with special
      reference to ventriculography].

PMID- 14951302
TI  - [Treatment of injuries of the anterior region of the basicranium].

PMID- 14951303
TI  - [Pathogenesis and prognosis of otogenous facial paralysis].

PMID- 14951304
TI  - [Clinical aspects and effect of Coramin-Adenosin].

PMID- 14951305
TI  - [Epiphyseal growth in congenital syphilis].

PMID- 14951306
TI  - [Combined analgesic, spasmolytic and sedative therapy in stenocardia].

PMID- 14951307
TI  - [Results of the Gastein cure].

PMID- 14951308
TI  - [A danger of penicillin therapy].

PMID- 14951309
TI  - [Surgical experiences with antibiotics and chemotherapy].

PMID- 14951310
TI  - [Prophylaxis of genital carcinomas].

PMID- 14951311
TI  - [Radioiodine studies of thyroid metabolism].

PMID- 14951312
TI  - [Case of allergic meningitis].

PMID- 14951313
TI  - [Influenzal pneumonia].

PMID- 14951314
TI  - [Tendon transplantation in paralysis of the peroneal nerve and the peroneal
      distribution of the sciatic].

PMID- 14951315
TI  - [Treatment of pancreatogenic Basedow's disease and thyreotoxicosis with a
      synthetic preparation of pancreatic enzymes].

PMID- 14951316
TI  - [Microdose roentgenotherapy of angina pectoris].

PMID- 14951317
TI  - [Cardiolipin and other alcoholic myocardial extracts].

PMID- 14951318
TI  - [Treatment of tuberculosis in childhood].

PMID- 14951319
TI  - [Bone dangers in Aleppo boil].

PMID- 14951320
TI  - [Mode of action of salicylate-pyramidon mixtures].

PMID- 14951321
TI  - [Study of skin-reactions to oral sulfonamide treatment].

PMID- 14951322
TI  - [Myocain A in laparotomy].

PMID- 14951323
TI  - [Child psychiatry].

PMID- 14951324
TI  - [Experimental studies on nutrition with refined diet].

PMID- 14951325
TI  - [The effect of coramine-caffeine on the athletic performance].

PMID- 14951326
TI  - [Causes of sedimentation and comparative studies on the methods of determination
      of sedimentation rate].

PMID- 14951327
TI  - [Results of conservative therapy of adnexal diseases].

PMID- 14951328
TI  - [On unspecific serological reactions].

PMID- 14951329
TI  - [Intravenous administration of a new cholesterine ester in animal experiment;
      preliminary report].

PMID- 14951330
TI  - [Therapeutic results and complications in perityphilitic abscess].

PMID- 14951331
TI  - [Greeting address at the inaugural meeting of the Society of Insurance Physicians
      of Austria].

PMID- 14951332
TI  - [Expert testimony in neurological consequences of accidents].

PMID- 14951333
TI  - [The therapy of the varicose ulcer].

PMID- 14951334
TI  - [Electronoptic examination of human suspects of foot-and-mouth disease].

PMID- 14951335
TI  - [Otitis media and dyspepsia in infant].

PMID- 14951336
TI  - [Society of Insurance Physicians of Austria, purpose and objectives].

PMID- 14951337
TI  - [Surgery after accidents and social security].

PMID- 14951338
TI  - [Injuries from permanent-wave service under heat application].

PMID- 14951339
TI  - [Experimental studies on the antiulcus factor in liquorice root].

PMID- 14951340
TI  - [Hyaluronidase].

PMID- 14951341
TI  - [Expert testimony in the field of the internist].

PMID- 14951342
TI  - [Evaluation of microscopic urine analysis in diagnosis of cancer].

PMID- 14951343
TI  - [Incidence, diagnosis and therapy of carcinoma colli uteri with special reference
      to the preinvasive carcinoma].

PMID- 14951344
TI  - [Critical remarks on Kment's article: Effects of tissue extracts on the function
      of the connective tissue (reticuloendothelial system) and blood vessels].

PMID- 14951345
TI  - [Disorders of ventilation and blood circulation of the lung caused by the
      enlarged left atrium].

PMID- 14951346
TI  - [Roentgen irradiation of the epigastric region in polycythemia rubra vera].

PMID- 14951347
TI  - [Statistic evaluation of carcinoma of the breast].

PMID- 14951348
TI  - [On roentgen therapy of neuralgias].

PMID- 14951349
TI  - [On x-ray irradiation of the entire body in malign tumors with reference to its
      use as a prophylactic after treatment].

PMID- 14951350
TI  - [Interstitial pulmonary fibrosis in scleroderma].

PMID- 14951351
TI  - [Roentgen council and roentgen control examination].

PMID- 14951352
TI  - [On spondylitis tuberculosa anterior].

PMID- 14951353
TI  - [Incidence of goiter in Austria].

PMID- 14951354
TI  - [On pituitary disorders in psychoneuroses].

PMID- 14951355
TI  - [The use of noradrenalin during and after surgery].

PMID- 14951356
TI  - [On the prevention of postoperative blood circulation disorders].

PMID- 14951357
TI  - [Toxic strychnine dosis in barbiturate poisoning].

PMID- 14951358
TI  - [On surgery of female sterility].

PMID- 14951359
TI  - [X ray hypersensitivity caused by phenylin].

PMID- 14951360
TI  - [Pulmonary cyst with abnormal arterial blood supply].

PMID- 14951361
TI  - [Mononucleosis infectiosa].

PMID- 14951362
TI  - [Incidence of goiter in school children in Bad-Hall and surroundings].

PMID- 14951363
TI  - [Psychical prevention of convulsions].

PMID- 14951365
TI  - [Exploratory laparotomy].

PMID- 14951364
TI  - [Evaluation of the prostigmine test in diagnosis of diseases of the pancreas].

PMID- 14951366
TI  - [Goiter as a deficiency disease].

PMID- 14951367
TI  - [Sympathectomy and sexual functions].

PMID- 14951368
TI  - [Diagnosis of leptospirosis].

PMID- 14951369
TI  - [On a causal therapy of the varicous ulcer].

PMID- 14951370
TI  - [Torsion of the omentum].

PMID- 14951371
TI  - [The danger of ultrasonics].

PMID- 14951372
TI  - [Studies on the viscosity of the blood in iodine application with a new
      viscosimeter arrangement].

PMID- 14951373
TI  - [Therapy of anxiety].

PMID- 14951374
TI  - [Circulatory disorders in general anesthesia and its therapy].

PMID- 14951375
TI  - [Basis for a reclassification of the hematology of cellular reactions in the
      lymphatic system].

PMID- 14951376
TI  - [The nucleolus of lymphocytes; I. Fixation and physiology of nucleolus].

PMID- 14951377
TI  - [Serum iron in chronic polyarthritis].

PMID- 14951378
TI  - [Effects of cortisone and ACTH on permeability of capillaries].

PMID- 14951379
TI  - [Vectorcardiographic findings in mitral stenosis and cor pulmonale].

PMID- 14951380
TI  - [Electrophoretic investigations on the mechanism of transsudation caused by
      congestion].

PMID- 14951381
TI  - [Vienna Society for Internal Medicine].

PMID- 14951382
TI  - Roentgen therapy in pituitary adenomas.

PMID- 14951383
TI  - Secondary abdominal pregnancy of five months' duration terminated by laparotomy.

PMID- 14951384
TI  - A reformed mealtime schedule; its effect on weight and serum glucose of
      tuberculous children.

PMID- 14951385
TI  - Hodgkin's disease of the stomach.

PMID- 14951386
TI  - Signs and symptoms of certain anxiety reactions.

PMID- 14951387
TI  - Atherosclerosis, lipoproteins, and coronary artery disease.

PMID- 14951388
TI  - Housing the migrant worker; as it looks to the state board of health.

PMID- 14951389
TI  - Acquirement of resistance to noxious agents.

PMID- 14951390
TI  - CLINICOPATHOLOGIC Conference.

PMID- 14951391
TI  - EXPERT committee on insecticides; third report.

PMID- 14951392
TI  - Francis Gilman Blake 1887-1952.

PMID- 14951393
TI  - The study of serum proteins and lipids with the aid of the quantity
      ultracentrifuge. VII. Some features of system of lipoproteins which contain
      phospholipid but no free cholesterol.

PMID- 14951394
TI  - Corticotropin and cortisone in diseases of the nervous system.

PMID- 14951395
TI  - Experimental production of gynecomastia with chorionic gonadotropin.

PMID- 14951396
TI  - Relative polycythemia; the polycythemia of stress.

PMID- 14951397
TI  - The treatment of hypertension: a fifteen-year follow-up.

PMID- 14951398
TI  - Purpura variolosa; its manifestations in skin and blood.

PMID- 14951399
TI  - The action of crystalline trypsin and soybean trypsin inhibitor on the clotting
      of blood by staphylocoagulase.

PMID- 14951400
TI  - A study of the cutaneous reactions to oidiomycin, trichophytin, and mumps skin
      test antigens in patients with sarcoidosis.

PMID- 14951401
TI  - The effect of DOCA on electrolyte balance in normal man and its relation to
      sodium chloride intake.

PMID- 14951402
TI  - Inhibition of influenza virus multiplication by 2,5-dimethylbenzimidazole.

PMID- 14951403
TI  - Francis Gilman Blake.

PMID- 14951404
TI  - Remembrance of Dr. Blake.

PMID- 14951405
TI  - Francis Gilman Blake.

PMID- 14951406
TI  - Studies on the killed tuberculosis vaccine. I. Active immunization against
      experimental tuberculosis in guinea pigs with vaccine, rendered nonviable by
      Merzonin and heat.

PMID- 14951407
TI  - Studies on the rabies vaccine. VII. On an assay technique of anti-rabies vaccine.

PMID- 14951408
TI  - Hemagglutination reaction of sensitized fowl erythrocytes in urogenital
      tuberculosis.

PMID- 14951409
TI  - Investigations of hookworm larvae. I. On the phototropism of infective larvae of
      Ancylostoma caninum.

PMID- 14951410
TI  - Studies on blood count. I. The distribution type of blood corpuscles in small
      squares of haemocytometer.

PMID- 14951412
TI  - 8TH MEETING of the Yokohama Medical Association; the meeting was held at the
      auditorium of Yokohama University School of Medicine on November 18, 1951.

PMID- 14951411
TI  - [Reply on the remarks of the discussion of Dr. Fritz Driak in Vienna].

PMID- 14951413
TI  - [Trachoma in STO; critical evaluation of epidemics of trachoma and survey of the
      zone B].

PMID- 14951414
TI  - [Medico-legal aspects of anesthesia].

PMID- 14951415
TI  - [Perforation of gastroduodenal ulcer].

PMID- 14951416
TI  - [Vascular diseases of the brain and their surgical therapy].

PMID- 14951417
TI  - [Prognostic value of frog tests in impaired pregnancy].

PMID- 14951418
TI  - [Vaginal smear].

PMID- 14951419
TI  - [Ophthalmology in general practice].

PMID- 14951420
TI  - [Amandus Hahn].

PMID- 14951421
TI  - [Power and velocity of the elastic after-contraction in the inactive frog muscle;
      with a contribution on Hill's equation].

PMID- 14951422
TI  - [Non-parabiotic forms of repeated reaction to stimulation on the
      catelectronically polarized nerve of cold blood animal].

PMID- 14951423
TI  - [On the Pulfrich phenomenon].

PMID- 14951424
TI  - [A new manometric probe with electrical transmission].

PMID- 14951425
TI  - [Stereo-optic sense].

PMID- 14951426
TI  - [Demonstration of male hormones in pregnant urine and placenta].

PMID- 14951427
TI  - [Recent studies on the effect of placental substances on growth and
      differentiation in mammals].

PMID- 14951428
TI  - [Justification of the expression, decidual reaction].

PMID- 14951429
TI  - [Clinical treatment and histology of colloid carcinoma of the uterine cervix].

PMID- 14951430
TI  - [Therapeutic results in primary ovarian carcinoma in the Barmbek hospital].

PMID- 14951431
TI  - [Clinical treatment and pathology of primary carcinoma of the fallopian tubes].

PMID- 14951432
TI  - [Modern mustard gas and ether anesthesia in closed circuit].

PMID- 14951433
TI  - [Sexual intercourse as therapy].

PMID- 14951434
TI  - [Ambulant colpoepisioclisia in senile prolapse].

PMID- 14951435
TI  - [Manifestly sterile periods in the lives of fertile women].

PMID- 14951436
TI  - [Cytology of the amniotic fluid; membranal rupture diagnosis and sex prediction].

PMID- 14951437
TI  - [The relation between gonadotropic and thyrotropic function; animal experiments].

PMID- 14951438
TI  - [Thyroid function as criterion of functional changes of estrogen in various
      therapeutic use; animal experiments].

PMID- 14951439
TI  - [Neurofibromatosis of the uterus].

PMID- 14951440
TI  - [Contra sexual hormone therapy of female genital carcinoma].

PMID- 14951441
TI  - [Gynecological importance of the hyaluronic acid-hyaluronidase system;
      therapeutic use of the hyaluronidase preparation kinetin].

PMID- 14951442
TI  - [Diaplacental transmission of scarlet fever in newborn; case report].

PMID- 14951443
TI  - [Morphological changes of Trichomonas vaginalis].

PMID- 14951444
TI  - [Effects of castration on the central nervous system].

PMID- 14951445
TI  - [Relation of the daily volume of urine to the excretion of C17-ketosteroids and
      the so-called corticoids].

PMID- 14951446
TI  - [Effect of hypophysectomy on the course of experimental diphtherial intoxication
      in guinea pigs].

PMID- 14951447
TI  - [Regulation of the blood cell concentration. I].

PMID- 14951448
TI  - [Methodology of continuous blood pressure measurement in non-narcotized animal].

PMID- 14951449
TI  - [The 24-hour rhythm of intramuscular pressure and its relation to water
      metabolism].

PMID- 14951450
TI  - [Renal excretion and mode of action of carinamide (Staticin)].

PMID- 14951451
TI  - [Mechanism of carinamide's effect on renal penicillin excretion and penicillin
      blood concentration].

PMID- 14951452
TI  - [Relation between vitamin E and the male sex hormone; 17-ketosteroid excretion
      after oral administration of alpha-tocopherol acetate in the healthy male].

PMID- 14951453
TI  - [On the demonstration of complement binding auto-antibodies in kidney and liver
      disease].

PMID- 14951454
TI  - [Observation of the lungs of experimental animals intra vitamin].

PMID- 14951455
TI  - [Dysproteinemia and myocardosis; experimental studies on rats].

PMID- 14951456
TI  - [The effect of adrenalin on the isolated sphincter iridis].

PMID- 14951457
TI  - [S35-tagged yeast in the feed of rabbits; studies on intestinal yeast protein
      cleavage, resorption and organ distribution of S35-thioaminoacids].

PMID- 14951458
TI  - [Mechanism of the uptake of plasma-protein-bound dyes by the reticuloendothelial
      system; a contribution on the problem of cell membrane permeability].

PMID- 14951459
TI  - [Chemical and crystalline demonstration of androgens and corticoids in urine and
      tumor tissue in cases of virilizing ovarian tumor].

PMID- 14951460
TI  - [Biologically and chemically produced thrombin].

PMID- 14951461
TI  - [Longevity of transfused erythrocytes in kidney disease; a contribution on the
      pathogenesis of nephrogenous anaemia].

PMID- 14951462
TI  - [Experimental studies on the effect of ganglion blocking agents on acral blood
      circulation in relation to the degree of sensitization].

PMID- 14951463
TI  - [Effect of liver extracts on cobalt therapy of experimental anemia in animals].

PMID- 14951464
TI  - [New aspects in research of gonorrhea].

PMID- 14951465
TI  - [On the retention of arsenic in the body after salvarsan exanthema].

PMID- 14951466
TI  - [Anatomic-histological studies on involution processes of specific liver changes
      in lues connata after penicillin].

PMID- 14951467
TI  - [On occupational cancer of the skin].

PMID- 14951468
TI  - [On side effects on the skin in vitamin D 2 therapy of skin tuberculosis].

PMID- 14951469
TI  - [The present status of medical mycology].

PMID- 14951470
TI  - [In memory of Carl Moncorps].

PMID- 14951471
TI  - [New results of therapy with antihistaminics].

PMID- 14951472
TI  - [Skin eruptions caused by new antiepileptics (mesantoin)].

PMID- 14951473
TI  - [Unusual case of hair knot formation].

PMID- 14951474
TI  - [Therapy of progressive scleroderma].

PMID- 14951475
TI  - [Skin protection in very dirty work].

PMID- 14951476
TI  - [Report from the spring meeting of the South-German Dermatologists' Association,
      Mainz, April 28-29, 1951].

PMID- 14951477
TI  - [Manifestations of circulatory congestions on the lower legs; (Dermatopathia
      cyanotica Rost and ulcus cruris)].

PMID- 14951478
TI  - [The different eczemata of the hands].

PMID- 14951479
TI  - [Etiology of pain sensation in dermatoleiomyomata].

PMID- 14951480
TI  - [Naevus flammeus tardivus (effect of cold)].

PMID- 14951481
TI  - [Treponematoses, an important problem of public health service; international
      efforts of the World Health Organization to combat yaws and syphilis].

PMID- 14951482
TI  - [Diseases of the lower legs caused by faulty blood circulation (dermatopathia
      cyanotica Rost & ulcus cruris)].

PMID- 14951483
TI  - [Malaria urticata].

PMID- 14951484
TI  - [New knowledge on the effect of hormones on local disease; therapeutic use].

PMID- 14951485
TI  - [Antimycotic therapy with special reference to fatty acids dissolved molecularly
      in leucichthol].

PMID- 14951486
TI  - [Therapy of epidermophytia pedum with ortho-vanilline].

PMID- 14951487
TI  - [Report from the spring meeting of the South-German Dermatologists' Association,
      Mainz, April 28-29, 1951].

PMID- 14951488
TI  - [Symptoms of B avitaminoses of the skin].

PMID- 14951489
TI  - [A new therapy of xanthomatosis].

PMID- 14951490
TI  - [Correlation of resistance of neisseria gonorrhea].

PMID- 14951491
TI  - [A new method in therapy of prostatitis].

PMID- 14951492
TI  - [The federal law for control of venereal diseases].

PMID- 14951493
TI  - [Effects of syphilis on the history of mankind].

PMID- 14951494
TI  - [Report from the spring meeting of the South-German Dermatologists' Association,
      Mainz, April 28-29, 1951].

PMID- 14951495
TI  - [On the antibacterial effect of saliva].

PMID- 14951496
TI  - [Measurement of the tuberculostatic action of chemical compounds].

PMID- 14951497
TI  - [An inoculation chamber for the prevention of laboratory infections and secondary
      contamination of cultures].

PMID- 14951498
TI  - [On the most suitable method of making serial bacterial counts of milk].

PMID- 14951499
TI  - [A year's intensified campaign against typhoid in Schleswig-Holstein].

PMID- 14951500
TI  - [Steam sterilization, a new method for the defestation of soil; a contribution on
      food hygiene].

PMID- 14951501
TI  - [A new thermolabile somatic antigen of gram-negative enteric bacteria].

PMID- 14951502
TI  - [An examination of the Costa reaction in diphtheria, scarlet fever & typhoid].

PMID- 14951503
TI  - [Studies on Oxyuris. I. Ova in dirt under the nails and in household dust].

PMID- 14951504
TI  - [Value and efficacy of Griffith's medium in the culture of the tubercle bacillus
      from pathologic material].

PMID- 14951505
TI  - [Statistics on postvaccinal immunity in naturally acquired typhus].

PMID- 14951506
TI  - [Cellulose-reducing micro-organisms].

PMID- 14951507
TI  - [Epidemiological development of poliomyelitis in Berlin, 1945-50].

PMID- 14951508
TI  - [Bacteriologic examination of the stool and urine of typhoid carriers].

PMID- 14951509
TI  - [Effect of MX, a harmless preservative in the prevention of infection by milk
      deliberately inoculated with S. breslau].

PMID- 14951510
TI  - [Laboratory differential diagnosis of dysenteric diseases].

PMID- 14951511
TI  - [Changes in the erythrocytes caused by Vibrio cholerae and by trypsin].

PMID- 14951512
TI  - [Experiments in the culture of Spirilla and certain pathogenic protozoa in the
      isolated cheek pouch of the golden hamster].

PMID- 14951513
TI  - [Changes of gram-negative bacteria under conditions of deficiency].

PMID- 14951514
TI  - [Value of an intracutaneous test in preventing complications of typhoid and
      paratyphoid vaccination].

PMID- 14951515
TI  - [Differentiation of types of the Clostridium welchii group with the aid of
      hemagglutination inhibition test].

PMID- 14951516
TI  - [Disinfection of waste water from tuberculosis sanatorium].

PMID- 14951517
TI  - [Physical characteristics of germicidal aerosols and artificial germ-laden
      mists].

PMID- 14951518
TI  - [The bacteriostatic and bactericidal effect of the celomic fluid of ascarids].

PMID- 14951519
TI  - [Darzins' shaking-precipitation method in primary isolation of the tubercle
      bacillus from pathologic material].

PMID- 14951520
TI  - [Fish as a source of disease in man].

PMID- 14951521
TI  - [Experimental studies on moniliasis; with a contribution to the Castelli-Gaggini
      serodiagnosis of cancer with Oidium albicans].

PMID- 14951522
TI  - [A solid medium for permanent cultures of pathogenic Leptospira].

PMID- 14951523
TI  - [Proposals on milk hygiene].

PMID- 14951524
TI  - [On the examination of dust in hygiene and meteorology].

PMID- 14951525
TI  - [Bactericidal and virucidal effect of aureomycin, terramycin and chloromycetin on
      calf lymph].

PMID- 14951526
TI  - Experience with the Antirabic Vaccination in the two World Wars.

PMID- 14951527
TI  - [Further tests on the sterility and stability of streptomycin lymphs].

PMID- 14951528
TI  - [On prophylaxis, pathogenesis and therapy of pylorospasm].

PMID- 14951529
TI  - [Antibiotics of animal origin].

PMID- 14951530
TI  - [Hydrogen peroxide production by gram-negative bacteria; with a contribution on
      the identification of H2O2-forming microorganisms].

PMID- 14951531
TI  - [Experiments with rabbits on the effect of cobalt on the antibody titer of the
      blood].

PMID- 14951532
TI  - [The significance of the Essen tuberculosis antigen in the diagnosis of
      tuberculous meningitis].

PMID- 14951533
TI  - The Coxsackie Viruses; with a consideration of their Relationship to the Virus of
      Poliomyelitis; a review.

PMID- 14951534
TI  - [Effect of tetraiodophenolphthalein on bacteria of the TPE group].

PMID- 14951535
TI  - [On the problem of anti-antibodies; experiments with anti-A and anti-O
      hemaglutinins from plants].

PMID- 14951536
TI  - [Neurotropic viruses recently discovered in Africa].

PMID- 14951537
TI  - [Comparative demonstration of the equivalents of nuclei of coli bacteria in
      light, phase contrast and electronic microscope].

PMID- 14951538
TI  - [Quantitative complement fixation reaction (Wassermann reaction) in diagnosis of
      syphilis].

PMID- 14951539
TI  - [Hepatitis epidemica in Nordrhein-Westfalen in the years 1949-1950].

PMID- 14951540
TI  - [Staining of tubercle bacilli with Sudan black BN].

PMID- 14951541
TI  - [Differentiation of bacteria of the alcaligenes group. I. Morphology and
      physiology].

PMID- 14951542
TI  - [Production of Rh subgroup sera for forensic purposes].

PMID- 14951543
TI  - [Differentiation of bacteria of the alcaligenes group; II. Serology].

PMID- 14951544
TI  - [Second report on the propagation of tularemia into middle and western Europe in
      present time; geomedical investigations on the development in the last decade and
      epidemiological prognosis].

PMID- 14951545
TI  - [Differentiation of freshly isolated strains of mycobacterium tuberculosis
      hominis et bovis in culture and rabbit inoculation].

PMID- 14951546
TI  - [Paracoli strains of the Bethesda group in the diagnosis of pathogenic intestinal
      bacterial].

PMID- 14951547
TI  - [Effects of alkali, especially of sodium bicarbonate, on the bactericidity of
      boiling formaldehyde solutions].

PMID- 14951548
TI  - [Drosophila fauna in Southwest Europe].

PMID- 14951549
TI  - [Systematics of Drosophila varieties of Southwest Europe].

PMID- 14951550
TI  - [Precipitation of chromosome mutations in meiosis by deep temperatures].

PMID- 14951551
TI  - [Natural polyploidia in planaria Dendrocoelum lacteum (Mueller) and Dendrocoelum
      infernale (Steinmann)].

PMID- 14951552
TI  - [New ideas on the problem of extra nuclear hereditary transmission].

PMID- 14951553
TI  - [Effect of selection on chemically induced neoplasms in mice].

PMID- 14951554
TI  - [Importance of acid and alkaline phosphatase in diagnosis of neoplasms].

PMID- 14951555
TI  - [Involvement of mesenchyma in experimental induction of skin carcinoma of mice by
      benzpyrene].

PMID- 14951556
TI  - [Carcinogenous effects of beta-naphthylamine].

PMID- 14951557
TI  - [Effect of fluorescent dyes on transplantable neoplasms].

PMID- 14951558
TI  - [Neoplasms and regulated dependent disorders of growth (hyperplasias) seen from
      the viewpoint of cellular and relational pathology].

PMID- 14951559
TI  - [Intra- and extragenital multiplicity of neoplasms in female genital carcinoma;
      results of an extensive anatomical, clinical and statistical evaluation of over
      4000 genital neoplasms].

PMID- 14951560
TI  - [On the spatial position of the integral vectors in Fallots' tetralogy and the
      Eisenmenger complex].

PMID- 14951561
TI  - [A simple method to determine the main direction of the frontal vector loop].

PMID- 14951562
TI  - [Effect of inhibition of the carotid sinus reflex on the small circulation].

PMID- 14951563
TI  - [Determination of time of blood circulation with decholin and ether in congenital
      heart diseases].

PMID- 14951564
TI  - [A method of further subclassification of the frontal leads by additional leads].

PMID- 14951565
TI  - [On three heart cases with severe pressure increase in the small circulation for
      special reasons].

PMID- 14951566
TI  - [On sympatol and the pacemakers of the human heart].

PMID- 14951567
TI  - [The question of electromechanic & electropressor period of latency & the so
      called stretching time of the heart].

PMID- 14951568
TI  - [A new method to determine the peripheral blood supply at any region of the
      body].

PMID- 14951569
TI  - [Tricuspid atresia in a 21 year old man].

PMID- 14951570
TI  - [A formal principle of combination of developmental abnormalities of the venous &
      arterial ventricular ostia].

PMID- 14951571
TI  - [Investigations on beginning & development of the effect of digitoxin on the
      heart in therapeutic application].

PMID- 14951572
TI  - [The so-called vector cardiogram with special consideration of the vectorial
      interpretation of the esophageal cardiograms].

PMID- 14951574
TI  - [The analyzed relief of potential of the unipolar thoracic leads].

PMID- 14951573
TI  - [Attempt to determine the vectors from precordial leads].

PMID- 14951575
TI  - [Studies on Weber's test and its dependence on pitch; an attempt at
      objectivization of the test].

PMID- 14951576
TI  - [Electrographic nystagmus recording].

PMID- 14951577
TI  - [Reliability of intensity records in audiometry].

PMID- 14951578
TI  - [Deaf-mutism, vestibulary damage and external ear malformation as symptoms of
      rubella embryopathy].

PMID- 14951579
TI  - [Use of hyaluronidase in otorhinolaryngology].

PMID- 14951580
TI  - [Absence of arrectores pilorum muscles in the external ear and on the nose].

PMID- 14951581
TI  - [Removal of pneumatic cells of the mastoid process in surgical fenestration].

PMID- 14951582
TI  - [Investigations on Weber's test and its relation to the height of sounds; II.
      Investigations on the relation between frequency and lateralization in Weber's
      test].

PMID- 14951583
TI  - [Comparison of the tuning fork with the audiometer test].

PMID- 14951584
TI  - [A new possibility of simulation tests].

PMID- 14951585
TI  - [Observations on the direction of secretion and ciliar motion on the mucous
      membranes of the nose and the nasopharynx].

PMID- 14951586
TI  - [Bacteriology of fibrinous otitis].

PMID- 14951587
TI  - [Pneumococcus mucosus and its independent pathogenicity].

PMID- 14951588
TI  - [Observations in unilaterally deaf twins].

PMID- 14951589
TI  - [Combined therapy of vasomotor rhinitis with submucous calcium injections and
      antihistaminics].

PMID- 14951590
TI  - [Evipan-Natrium anesthesia in otorhinolaryngological operations].

PMID- 14951591
TI  - [Size of cell nucleus and so-called compensatory hypertrophy of the mouse
      kidney].

PMID- 14951592
TI  - [Constrictive muscles in the liver veins of the carp].

PMID- 14951593
TI  - [Mucoid secretion of the gall bladder].

PMID- 14951594
TI  - [Effects of colchicine on the primitive development of Triton palmatus].

PMID- 14951595
TI  - [The urogenital light-cell system of man].

PMID- 14951596
TI  - [Investigations on existence and form of intraarterial bodies in man and in the
      cat].

PMID- 14951597
TI  - [Double morphogenesis of the organism of vertebrates; primary (indirect) and
      secondary (direct) development].

PMID- 14951598
TI  - [Double development of the vertebrate body, seen from the viewpoint of
      preservation of function].

PMID- 14951599
TI  - [Innervation of the eye muscles of man].

PMID- 14951600
TI  - [Nuclear growth in follicles and corpora lutea in human ovaries].

PMID- 14951601
TI  - [Nuclear volume studies on the intestinal epithelium of the rat during different
      periods of starvation].

PMID- 14951602
TI  - [Morphology and histochemistry of the rump gland of ducks].

PMID- 14951603
TI  - [The spleen of the elk (Alces alces L.)].

PMID- 14951604
TI  - [The histochemical reactions of the normal urinary bladder mucous membrane].

PMID- 14951605
TI  - [Measurements of the energy consumption of thigh amputees with different
      prostheses].

PMID- 14951606
TI  - [Experimental contributions to the question of tendolipoidosis].

PMID- 14951607
TI  - [Experimental investigations on the pathological mechanism of spontaneous rupture
      of tendons].

PMID- 14951608
TI  - [Interspongious disc hernias].

PMID- 14951610
TI  - [Plastic operations on the hip joint].

PMID- 14951609
TI  - [Pathologic-anatomic changes of hip joint capsules in arthrosis deformans].

PMID- 14951611
TI  - [Determination of the torsion of the neck of the femur].

PMID- 14951612
TI  - [Torsion of the tibia causing a rare deformity].

PMID- 14951613
TI  - [Operative correction of instability of the knee and foot].

PMID- 14951614
TI  - [Specific tonicity of the muscles of the sole of the foot and the lower leg and
      its relation to foot deformities].

PMID- 14951615
TI  - [Mechanistic and localistic or general viewpoint in orthopedics].

PMID- 14951616
TI  - [Symmetric tarsal synostosis; with operative therapy of the resulting deformity].

PMID- 14951617
TI  - [Lumbal sympathetic block with oily anesthetic solution; histological findings].

PMID- 14951618
TI  - [Unusual painful conditions of the amputation stump].

PMID- 14951619
TI  - [Symmetrical synostoses of hand and feet].

PMID- 14951620
TI  - [Talipes equinus and Hemangioma].

PMID- 14951621
TI  - [First Congress of Orthopedics and Traumatology of Latin America].

PMID- 14951622
TI  - [Result of therapy of congenital lift luxation].

PMID- 14951623
TI  - [Structural changes of the hip joint after therapy of the congenital luxation].

PMID- 14951624
TI  - [Dysplasia, osteoarthritis and subluxation of the hip].

PMID- 14951625
TI  - [Experiences in plastic surgery of the hip joint with plastic prosthesis].

PMID- 14951626
TI  - [Symptoms & pathogenesis of congenital deformities and pseudarthroses of the
      lower leg].

PMID- 14951627
TI  - [Chronic osteomyelitis and Perthes disease].

PMID- 14951628
TI  - [Pathohistology of the congenital clubfoot; results of operations on clubfeet of
      the Orthopedic University Hospital in Rostock].

PMID- 14951629
TI  - [Ruptured intervertebral disc in leg amputees].

PMID- 14951630
TI  - [Experiences with pressure arthrodesis of the upper and lower ankle joint].

PMID- 14951631
TI  - [Knee pain of teen age girls].

PMID- 14951633
TI  - [Peter Bade - 80 years of age].

PMID- 14951632
TI  - [Typical knee pain in girls].

PMID- 14951634
TI  - [Franz Schede - 70. birthday on July 9, 1952].

PMID- 14951635
TI  - [Therapy of complete paralyses of the arm].

PMID- 14951636
TI  - [Propositions to change orthopedic nomenclature].

PMID- 14951637
TI  - [Improvements of therapeutic results to congenital dislocation of the hip].

PMID- 14951638
TI  - [Prognosis of the so-called congenital luxation of the hip].

PMID- 14951639
TI  - [Plastic joint operation in congenital hip luxations healed with deformity].

PMID- 14951640
TI  - [Late results of surgery of congenital dislocation of the hip].

PMID- 14951641
TI  - [Enlargement of the supporting joint surface as a therapeutic measure in
      arthrosis of the hip joint].

PMID- 14951642
TI  - [Therapy of the excavated foot by plastic tendon operation].

PMID- 14951643
TI  - [Clinical experiences in the operative therapy of the excavated foot by
      Erlacher's method].

PMID- 14951644
TI  - [Etiology and pathogenesis of the muscular torticollis].

PMID- 14951645
TI  - [Peteosthor in tuberculous osteomyelitis and arthritis; report of experience].

PMID- 14951646
TI  - [Therapy of arthrosis of the hip joint; with a report on the use of metallic
      prostheses in the vanishing of the head and neck of the femur].

PMID- 14951647
TI  - [Arthroplastic operation of the hip joint with special endoprosthesis].

PMID- 14951648
TI  - [Functional adaptation of the bone; demonstration of selected x-ray pictures].

PMID- 14951649
TI  - [A mobile redression corset for scolioses].

PMID- 14951650
TI  - [Investigation of the dynamics in the gait of the normal and amputated].

PMID- 14951651
TI  - [Technical novelties for the orthopedic practice].

PMID- 14951652
TI  - [A reading desk developed in the care of orthopedic patients].

PMID- 14951654
TI  - A contribution to the biology of Stenobracon deesae Cameron (braconidae,
      hymenoptera), and the anatomy of its pre imaginal stages.

PMID- 14951653
TI  - [Obituary for lecturing professor Dr. R. Elle].

PMID- 14951655
TI  - [Gordioidea: systematic study of insect parasites of the Nematomorpha class].

PMID- 14951656
TI  - [Biology and development of Trichobilharzia Szidati N. Sp. (Trematoda,
      Schistosmatidae), a parasite causing dermatitis in man].

PMID- 14951657
TI  - [To Albrecht Hase on his 70th birthday].

PMID- 14951658
TI  - [Biography].

PMID- 14951659
TI  - [On morphology of Strongylus vulgaris (Nematoda)].

PMID- 14951660
TI  - [Paracletus cimiciformis v. d. Heyd., and its parasitic adaptation to the ant
      host].

PMID- 14951661
TI  - [Reaction of the epidermis in scaly-leg of fowl caused by Cnemidocoptes
      (Sarcoptidae)].

PMID- 14951662
TI  - [The histopathology of parasitic infestation in certain of the ants].

PMID- 14951663
TI  - [The anatomy of Hedrusis mucronifer n. sp., and its parasitic adaptation to the
      host].

PMID- 14951664
TI  - [Phases of life and psychotherapy].

PMID- 14951665
TI  - [Graphologic-clinical investigations on patients with angina pectoris].

PMID- 14951666
TI  - [Phantom pain].

PMID- 14951667
TI  - [Suffering and art; a way in psychotherapy].

PMID- 14951668
TI  - [Rainer Maria Rilke, psyche and work. II. His possy as a picture of his
      personality].

PMID- 14951669
TI  - [Importance of humoral factors in the course of rheumatism].

PMID- 14951670
TI  - [Allergic-hyperergic inflammation of the adrenal cortex].

PMID- 14951671
TI  - [Clinical importance of antistreptokinase and antihyaluronidase titer].

PMID- 14951672
TI  - [Glucuronic acid metabolism in rheumatic diseases].

PMID- 14951673
TI  - [The anatomic position of rheumatic endocarditis].

PMID- 14951674
TI  - [Senile ankylosing hyperostosis of the vertebral column (Forestier-Rotes)].

PMID- 14951675
TI  - [Experimental investigations on the effects of salicylic acid].

PMID- 14951676
TI  - [Report from the meeting of the Swiss Society for Physical Medicine and
      Rheumatology, Luzern, November 3-4, 1951].

PMID- 14951677
TI  - [Histological examinations of virus inoculated chorion-allantois membranes of
      inoculated chicken eggs].

PMID- 14951678
TI  - [The results of rabies vaccination of man after wolf bite].

PMID- 14951679
TI  - [Q fever research in Switzerland in the years 1947-1951].

PMID- 14951680
TI  - [Experimental infection of Phthirus pubis L. with Rickettsia prowazeki and
      Rickettsia quintana].

PMID- 14951681
TI  - [Etiology of rat bite fever].

PMID- 14951682
TI  - [New investigations on Bartonella bacilliformis. I. Morphology of cultured
      variety].

PMID- 14951683
TI  - [Additional investigations on the toxoplasmosis complement fixation reaction of
      Westphal; comparison to the Sabin-Feldman reaction].

PMID- 14951684
TI  - [Sabin-Feldman test and Westphals complement fixation reaction in pulmonary
      tuberculosis].

PMID- 14951685
TI  - [Amebiasis in Great Britain].

PMID- 14951686
TI  - [Biology of Strongyloides].

PMID- 14951687
TI  - [The rare round worm infections of man].

PMID- 14951688
TI  - [A new therapy of trichocephaliasis].

PMID- 14951689
TI  - [Health conditions and development of Brasilians of German descent in the state
      Espirito Santo].

PMID- 14951690
TI  - [Infectious diseases in Southern Persia (county of Soussanguerd)].

PMID- 14951691
TI  - [Vitamin B deficiency syndrome (subacute Beri-Beri)].

PMID- 14951692
TI  - [Stevens-Johnson syndrome].

PMID- 14951693
TI  - [Clinical importance of the geographic distribution of tularemia].

PMID- 14951694
TI  - [Malaria plasmodia in the agglutinated thick drop preparation].

PMID- 14951695
TI  - [Essential hematuria].

PMID- 14951696
TI  - [Acidosis caused by anastomoses between intestines and ureters].

PMID- 14951697
TI  - [Abortive therapy of prostate hypertrophy].

PMID- 14951698
TI  - [Persistency of the primordial kidney or the nephrogenic mesoblastem with
      hemartia in the left kidney region].

PMID- 14951699
TI  - [The so called malacoplacia of the urinary bladder].

PMID- 14951700
TI  - [Pathologic-anatomic investigations on neoplastic diseases of the prostate,
      especially of the carcinoma].

PMID- 14951701
TI  - [Unusually large kidney calculus without history].

PMID- 14951702
TI  - [E. Pflaumer - 80. birthday].

PMID- 14951703
TI  - [Diseases of the ureters].

PMID- 14951704
TI  - [A new method of transillumination of the exposed kidney].

PMID- 14951705
TI  - [Therapy of benign and malignant prostate tumors with estrogens].

PMID- 14951706
TI  - [Diagnostic procedures in urologic patients].

PMID- 14951707
TI  - [Hypospadia operation of Denis Browe].

PMID- 14951708
TI  - [Urethral induration after use of indwelling catheter].

PMID- 14951709
TI  - [Therapy of metastases of a hypernephroma with contra sexual hormones].

PMID- 14951710
TI  - [Calculus in an ureterocele].

PMID- 14951711
TI  - [Meeting of the Austrian Urology Society].

PMID- 14951712
TI  - [Neurohistological findings on sympathetic ganglia of insufficient kidneys].

PMID- 14951713
TI  - [Experiences in the therapy of carcinomas of the prostate with estrogens].

PMID- 14951714
TI  - [Ureteral tumors].

PMID- 14951715
TI  - [Importance of physical rest as partial cause of urolithiasis].

PMID- 14951717
TI  - [Safety pin in the urethra].

PMID- 14951716
TI  - [Technique of cystometry and urethography in the woman].

PMID- 14951718
TI  - [Embryomae of kidney in adults].

PMID- 14951719
TI  - [Primary cortical focus of the renal tuberculosis].

PMID- 14951720
TI  - [Primary cortical focus of the renal tuberculosis].

PMID- 14951721
TI  - [Vulvo-urethral metastasis of a hyperephroma].

PMID- 14951722
TI  - [Abnormal position of the ureter in the iliac region].

PMID- 14951723
TI  - [Formation of bladder calculus by a shell fragment].

PMID- 14951724
TI  - [Recanalisation of mechanically closed ureters].

PMID- 14951725
TI  - [Rare metastases of carcinoma of the prostate in the testis, epididymis and
      ductus deferens].

PMID- 14951726
TI  - [Therapy of crustforming cystitis after operations on the bladder neck].

PMID- 14951727
TI  - [Ureteral cast calculus].

PMID- 14951728
TI  - [Simulation of an extrarenal tumor by a giant kidney pelvis in double kidney].

PMID- 14951729
TI  - [Bilateral hydronephrosis in prolapse of uterus].

PMID- 14951730
TI  - [Calculus in a bladder diverticulum in a woman].

PMID- 14951731
TI  - [Course of necrotizing papillitis].

PMID- 14951732
TI  - [Annual Meeting of the Swiss Urology Society].

PMID- 14951733
TI  - [Calculi in diverticula of the bladder].

PMID- 14951734
TI  - [Technique of the anastomosis between ureter and intestines].

PMID- 14951735
TI  - [Total cystectomy in carcinoma of the bladder performed in two step].

PMID- 14951736
TI  - [Vegetative nerve plexus in the ureter].

PMID- 14951737
TI  - [Echinococcus cyst of the kidney].

PMID- 14951738
TI  - [Urogenital trichomonas infection of the male].

PMID- 14951739
TI  - [Increase of streptomycin resistancy of E. coli infections of the urinary
      system].

PMID- 14951740
TI  - [Pyelitis gravidarum caused by right sided pyonephrosis with empyema of
      diverticulum of the ureter].

PMID- 14951741
TI  - [Rightsided hydronephrosis after vaginal total exstirpation of the uterus due to
      multiple myomata; chronic cholecystitis without concrement].

PMID- 14951742
TI  - [Not Available].

PMID- 14951743
TI  - [Meeting of the Austrian Urology Society].

PMID- 14951744
TI  - [Technique of plastic surgery of hydronephrotic kidneys].

PMID- 14951745
TI  - [Radical operation of carcinoma of the prostate].

PMID- 14951746
TI  - [Changes of knowledge of etiology of the benign hypertrophy of the prostate and
      their effects on therapy].

PMID- 14951747
TI  - [Disorders of the hydrodynamics of the uropoetic system and body fluids in
      patients with hypertrophy of prostate].

PMID- 14951748
TI  - [30 Years experience with ischiadic enucleation of the adenoma of the prostate
      (so-called prostate hypertrophy); with a critique of the other approaches].

PMID- 14951749
TI  - [Prostate surgery].

PMID- 14951750
TI  - [Anesthesia in bladder and prostate surgery].

PMID- 14951751
TI  - [Necessity of cardiovascular function tests in diseases of the uropoetic system;
      special consideration of the decholin-ether test].

PMID- 14951752
TI  - [Plastic repair of hypospadia with the Denis Browne method].

PMID- 14951753
TI  - [Retropneumoperitoneum].

PMID- 14951754
TI  - [Indications for nephropexy].

PMID- 14951755
TI  - [Genesis of aseptic kidney calculi].

PMID- 14951756
TI  - [Conservative therapy of ureteral cauculi of low location].

PMID- 14951757
TI  - [Antibiotic therapy of acute pyogenic urological diseases. II. Absceding
      prostatitis].

PMID- 14951758
TI  - [Focal infection and urogenital system].

PMID- 14951759
TI  - [Effects of chemotherapy on urogenital tuberculosis].

PMID- 14951760
TI  - [Pyelography after subcutaneous application of contrast medium; application of
      hyaluronidase].

PMID- 14951762
TI  - [Laws of harmony in the dynamics of the urinary tract].

PMID- 14951761
TI  - [Plastic bladder surgery with small intestines according to Scheele's method].

PMID- 14951763
TI  - [Hematuria in seemingly healthy kidneys].

PMID- 14951764
TI  - [Hypertension in unilateral kidney disease; experiments, case reports and
      practical consequences].

PMID- 14951765
TI  - [Endocrine symptoms in hypernephroma and their importance].

PMID- 14951766
TI  - [Severe pyogenic infections of the upper urinary tract; antibiotics therapy].

PMID- 14951767
TI  - [Extradural spinal anesthesia].

PMID- 14951768
TI  - [Surgery of functional urination disorders].

PMID- 14951769
TI  - [Great facetted kidney calculi].

PMID- 14951770
TI  - Photochemical transformation of chlorophyll explained according to the electronic
      theory.

PMID- 14951771
TI  - [Differentiation of gonadotropic hormones by comparative evaluation on rat &
      toad].

PMID- 14951772
TI  - [The origin of histamine in bees].

PMID- 14951773
TI  - [Method of determination of 17-ketosteroids].

PMID- 14951774
TI  - [Antiprothrombin in myelocytes].

PMID- 14951775
TI  - [Influence of factor T on digestive activities].

PMID- 14951776
TI  - [Clinical importance of pantothenic acid].

PMID- 14951777
TI  - [Vitamins in the human milk].

PMID- 14951778
TI  - [Insulin and bacterial phagocytosis of the leucocytes].

PMID- 14951779
TI  - [Influence on reproduction rate of paramecium caudatum Ehrbg. by vitamin B and
      amino acids].

PMID- 14951780
TI  - [Vitamin requirements of the confused flour beetle (Tribolium confusum Duval). I.
      The water-insoluble yeast fraction required by Tribolium confusum].

PMID- 14951781
TI  - [The physiological function of the pineal gland and its therapeutic application].

PMID- 14951782
TI  - [Metabolic changes following implantation of anterior pituitary tissue].

PMID- 14951783
TI  - [Effect of free nucleic bases on the growth of fibroblasts].

PMID- 14951784
TI  - A study of the golgi material of hepatic and intestinal epithelial cells with the
      electron microscope.

PMID- 14951785
TI  - [Peculiarities in the structure of small vessels in the periadventitial
      connective tissue of the ascending aorta].

PMID- 14951786
TI  - [The occurrence and mutual behavior of the argentaffin and argyrophil cells of
      the human gastrointestinal tract].

PMID- 14951787
TI  - [Studies of Sagitta setosa and Sagitta hexaptera in the polarization microscope].

PMID- 14951788
TI  - [Mesencephalic neurocrinia in birds].

PMID- 14951789
TI  - [Cytochemical and electronoptic studies of granular fractions of the bovine
      neurohypophysis].

PMID- 14951790
TI  - [Casuistics of congenital neoplasms: spindle cell sarcoma with extensive
      metastasis].

PMID- 14951791
TI  - [A microscopic choristoma of the adrenal cortex].

PMID- 14951792
TI  - [Primary carcinoma of the fallopian tubes].

PMID- 14951793
TI  - [The problem of the toxic liver dystrophy].

PMID- 14951794
TI  - [Extraperiosteal osteochondromatosis].

PMID- 14951795
TI  - [The question of legality of postmortem examination].

PMID- 14951796
TI  - [Malignant neurinoma of the bone].

PMID- 14951797
TI  - [Bone forming sarcoma of the thyroid gland].

PMID- 14951798
TI  - [Pathogenesis of fatty tissue on the visceral pleura].

PMID- 14951799
TI  - [Hemorrhages into the spleen tissue in myelocytic leukemia].

PMID- 14951800
TI  - [Nuclear inclusions in the human pancreas].

PMID- 14951802
TI  - [Chemistry of certain physiological and pathological growth].

PMID- 14951801
TI  - [Malignant degeneration of a glomus tumor of the great toe].

PMID- 14951803
TI  - [Toxic nephrosis].

PMID- 14951804
TI  - [Report from the the discussions at the Second Scientific Meeting of North-German
      Pathologists, Lubeck, September 22-23, 1951].

PMID- 14951805
TI  - [Vienna Pathologists' Association].

PMID- 14951806
TI  - [Spontaneous healing of a congenital heart defect].

PMID- 14951807
TI  - [An unusual form of lightning injury].

PMID- 14951808
TI  - [Arhinencephalia].

PMID- 14951809
TI  - [Gastrointestinal pathology in lymphatic leukemia].

PMID- 14951811
TI  - [Lung neoplasms caused by shell fragment].

PMID- 14951810
TI  - [Granuloblastomatous and scirrhous polypes of the stomach].

PMID- 14951812
TI  - [Meeting of the Berlin Pathologists' Association, October 30, 1951].

PMID- 14951813
TI  - [Pathologists' Association of Greater Hamburg].

PMID- 14951814
TI  - [Obturating tuberculous thrombophlebitis of the portal vein].

PMID- 14951815
TI  - [Histochemical determination of lipase activity in the liver].

PMID- 14951816
TI  - [Malformation of the tracheal skeleton with stenosis of the lumen in newborn].

PMID- 14951817
TI  - [A case of glycogenosis with deposition of glycogen in the peripheral nervous
      system].

PMID- 14951818
TI  - [A rare malformation of the aortic valves (chorda tendinea congenita in aorta)].

PMID- 14951819
TI  - [The Galt streptococcus causing ulcero-polypous endocarditis in man].

PMID- 14951820
TI  - [Endometritis; one hundred years of mucosal diagnosis].

PMID- 14951821
TI  - [Studies on the antlers of Cervus capreolus].

PMID- 14951822
TI  - [Meeting of the Berlin Pathologists' Association, December 4, 1951].

PMID- 14951823
TI  - [Pathologists' Association of Greater Hamburg].

PMID- 14951824
TI  - [50the anniversary of Max v. Pettenkoffer's death].

PMID- 14951825
TI  - [Otto Stickl].

PMID- 14951826
TI  - [Variations of the virus of the foot and mouth disease].

PMID- 14951827
TI  - [Elution and demonstration of a complement fixing antigen in adsorbing
      vaccination against foot-and-mouth disease].

PMID- 14951828
TI  - [Concentration of diphtheria bacilli in fluid media].

PMID- 14951829
TI  - [Evaluation of liquid media for concentration of salmonella].

PMID- 14951830
TI  - [Light and electron microscopic studies on the antibiotic varieties of
      Escherichia Coli].

PMID- 14951831
TI  - [Biology of different bacteria on saccharose media with special reference to the
      nuclear structures].

PMID- 14951832
TI  - [A new culture media for anaerobic bacteria].

PMID- 14951833
TI  - [Experiences with the cardiolipin complement fixation reaction of Pangborn and
      Kolmer].

PMID- 14951834
TI  - [An new apparatus for inoculation of culture media].

PMID- 14951835
TI  - [Experiences with novocain blocks of the sympathetic system].

PMID- 14951836
TI  - [Subtotal and total synovectomy in chronic nonspecific gonitis].

PMID- 14951837
TI  - [Unusual fracture and luxation of the hip joint with impossibility of
      reposition].

PMID- 14951838
TI  - [Therapy of luxation of os lunatum].

PMID- 14951839
TI  - [A new ergometer in diagnosis of peripheral vascular diseases].

PMID- 14951840
TI  - [Simple model of the Ansinn mountain climbing apparatus].

PMID- 14951841
TI  - [Experimental and clinical experiences with protocid].

PMID- 14951842
TI  - [Dangers in regional anesthesia in strumectomy].

PMID- 14951843
TI  - [Diffuse hemangiomatosis of spleen and skin].

PMID- 14951844
TI  - [Rupture of achilles tendon from its insertion].

PMID- 14951845
TI  - [Endarteritis tuberculosa].

PMID- 14951846
TI  - [Extraarticular osteodesis of the naviculare pseudoarthrosis of the hand].

PMID- 14951847
TI  - [66th Meeting of the Northwest-German Surgeons' Association].

PMID- 14951848
TI  - [Carcinoma and trauma].

PMID- 14951849
TI  - [Misinterpretation of a cavernous hemangioma of the knee capsule as incarcerated
      medial meniscus].

PMID- 14951850
TI  - [Dangerous arterial bleeding in the popliteal fossa].

PMID- 14951852
TI  - [104th Meeting of the Lower-Rhine-Westphalian Surgeons' Association].

PMID- 14951851
TI  - [Late results of nailed fractures of the neck of the femur].

PMID- 14951853
TI  - [Development of pareses of the recurrent nerve after strumectomy].

PMID- 14951854
TI  - [Anuria caused by sulfonamides].

PMID- 14951855
TI  - [Indications of local sulfonamide therapy in surgery].

PMID- 14951856
TI  - [Metastatic pus formation in the spinal peridural space].

PMID- 14951857
TI  - [Primary double carcinomata].

PMID- 14951858
TI  - [Two cases of carcinoma in scars].

PMID- 14951859
TI  - [Symptoms and pathology of synovialomata of the joints].

PMID- 14951860
TI  - [Rare localization of chondromatosis in a ganglion of the knee joint].

PMID- 14951861
TI  - [Emetin in the therapy of severe surgical infections].

PMID- 14951863
TI  - [Fractures of the spine in tetanus].

PMID- 14951862
TI  - [Mycotic aneurysm of the posterior tibial artery, the last focus of endocarditis
      lenta].

PMID- 14951865
TI  - [Osteomyelitis of patella].

PMID- 14951864
TI  - [Antibiotic therapy of osteomyelitis and articular empyemata in combination with
      surgical therapy].

PMID- 14951866
TI  - [Penicillin therapy of acute osteomyelitis; late results].

PMID- 14951867
TI  - [Georg Axhausen - 75. birthday].

PMID- 14951868
TI  - [Bone regeneration--a biphasic process].

PMID- 14951869
TI  - [Treatment of congenital coxa vara].

PMID- 14951870
TI  - [Experiences with the Herzer nail].

PMID- 14951871
TI  - [Bilateral rupture of the achilles tendon at different times].

PMID- 14951872
TI  - [Pseudoarthrosis of upper arm, used for active motions].

PMID- 14951873
TI  - [Critique of Wenzl's article: application of antibiotics to organs by
      intraarterial injection].

PMID- 14951874
TI  - [7. meeting of the Medial-Scientific Society for Surgery, Urology, Radiology and
      Orthopedics at the University of Leipzig].

PMID- 14951875
TI  - [Late surgery of bullets in heart; problem of bullet embolism].

PMID- 14951876
TI  - [Critique of pre- and postoperative therapy and surgery of gall bladder diseases
      in the last two years].

PMID- 14951878
TI  - [Postoperative reflectory anuria].

PMID- 14951877
TI  - [Surgery of phimosis; experiences with Schlaaf's method].

PMID- 14951879
TI  - [Early diagnosis of the carcinoma by fluorescency test in the serum; with the use
      of fluoresceine dodium].

PMID- 14951880
TI  - [Vision disturbances in surgical diseases].

PMID- 14951881
TI  - [Visual disturbances after surgery].

PMID- 14951882
TI  - [Sodium citrate intoxication causing transfusion damage].

PMID- 14951883
TI  - [Extensive resection of small and large intestines in one session].

PMID- 14951884
TI  - [Carcinoma of duodenal-jejunal flexure].

PMID- 14951885
TI  - [Arthrosis deformans of the hip joint; operative therapy by extirpation of the
      head of the femur and subtrochanteric osteotomy].

PMID- 14951886
TI  - [Use of peridural anesthesia in smaller hospitals].

PMID- 14951887
TI  - [Sympathetic block in multiple sclerosis].

PMID- 14951888
TI  - [Artificial emphysema of the scrotum with subcutaneous spreading over the trunk].

PMID- 14951890
TI  - [Surgery Association at the University of Berlin].

PMID- 14951889
TI  - [Meeting of the Surgery Association at the University of Leipzig, Dresden
      subsidiary].

PMID- 14951891
TI  - [Modern therapy of severe burns, with special reference to pancreatic ferment
      tylose mucilage therapy of Greuer-Gottingen].

PMID- 14951892
TI  - [A monstrous fibromyxosarcoma of the breast].

PMID- 14951893
TI  - [Carcinoma of the caecum on tuberculous basis].

PMID- 14951894
TI  - [Plastic grafting of the pars analis recti in operations for carcinoma of the
      rectum and sigmoid].

PMID- 14951895
TI  - [Plastic replacement of musculus spincter ani].

PMID- 14951897
TI  - [Synovaliomata].

PMID- 14951896
TI  - [Surgical removal of urethral fistulae].

PMID- 14951898
TI  - [Plastic ear surgery].

PMID- 14951899
TI  - [105. Meeting of the Lower-Rhine-Westphalian Surgeons' Association].

PMID- 14951900
TI  - [Chylothorax; surgical anatomy & x-ray demonstration of the thoracic duct].

PMID- 14951901
TI  - [Chylothorax; symptoms and etiology].

PMID- 14951902
TI  - [Total extirpation of the stomach].

PMID- 14951903
TI  - [Several observations in incarcerated herniae].

PMID- 14951904
TI  - [Foreign body inflammations after implantation of femur head prostheses made of
      polyurethan].

PMID- 14951905
TI  - [Phlebothrombosis of the upper extremity].

PMID- 14951906
TI  - [Peptic ulcer and surgery of the autonomic nervous system].

PMID- 14951907
TI  - [Late sequelae of chylothorax; indications for surgery of the thoracic duct].

PMID- 14951908
TI  - [Indication for cholecystectomy].

PMID- 14951909
TI  - [Retropubic (extravesical) prostatectomy].

PMID- 14951910
TI  - [Causes for tissue reaction in osteosynthesis using metals].

PMID- 14951911
TI  - [Denervation in painful arthrosis of the hip].

PMID- 14951912
TI  - [Retrograde amnesia seen from the viewpoint of synallaxes].

PMID- 14951913
TI  - [8. meeting of the Medial-Scientific Society for Surgery, Urology, Radiography
      and Orthopedics at the University of Leipzig].

PMID- 14951914
TI  - [Theory and practice in the use of cutis transplantations of E. Rehn..].

PMID- 14951915
TI  - [Massive aspiration of crushed sugar beets into the nasopharynx, trachea & main
      bronchi].

PMID- 14951916
TI  - [Rupture of spleen in two times].

PMID- 14951917
TI  - [Replacement of the pars pendula penis by a skin-cartilage graft].

PMID- 14951918
TI  - [Spontaneous aneurysm of the politeal artery with embolic gangrene of the foot].

PMID- 14951919
TI  - [Fixation of fractures difficult to retain in position by oblique nailing].

PMID- 14951920
TI  - [Surgery Association at the University of Berlin].

PMID- 14951921
TI  - [Treatment of prolapse of the genital organs with special consideration of
      Manchester-Fothergill's operation].

PMID- 14951922
TI  - [Surgical therapy of prolapse of the genital organs; Bumm's cervical fixation].

PMID- 14951923
TI  - [Bilateral bulbocavernosus plastic surgery of old perineal rupture repeatedly
      operated without success].

PMID- 14951924
TI  - [Technique and results of G. Doderlein's transverse pessary colporrhaphy].

PMID- 14951925
TI  - [Inhaler, Suhler model, for trichlorethylene analgesia].

PMID- 14951926
TI  - [Results with a new apparatus for obstetric trichloroethylene analgesia].

PMID- 14951927
TI  - [Comment on the article, Intravenous novocaine injection and infusion in
      analgesia, by Schmolling].

PMID- 14951928
TI  - [Congenital vaginal aplasia with solitary pelvic kidney].

PMID- 14951929
TI  - [Sources of urogenital trichomoniasis in women].

PMID- 14951930
TI  - [Successful injection treatment of functional bladder and rectal incontinence in
      women].

PMID- 14951931
TI  - [Treatment of urogenital fistulas].

PMID- 14951932
TI  - [Retention of urine due to changes in the female genitalia].

PMID- 14951933
TI  - [Healing of two bilateral ureteral-vaginal fistulas after Wertheim's abdominal
      radical operation by simultaneous implantation into the bladder].

PMID- 14951934
TI  - [Convention of the Deutsche Gesellschaft fur Urologie].

PMID- 14951935
TI  - [Full term pregnancy and live infant in a case of submucous uterine myoma the
      size of a fist].

PMID- 14951936
TI  - [Delivery of double monsters].

PMID- 14951937
TI  - [Prevention and control of eclampsia by a cholinester].

PMID- 14951938
TI  - [Delivery in mentoposterior brow presentation].

PMID- 14951939
TI  - [Comment on the article early injuries after pregnancy interruption by O. J.
      Granzow].

PMID- 14951940
TI  - [Tetanus following criminal abortion; case report].

PMID- 14951941
TI  - [Hemorrhage from the site of placental site attachment during and after the third
      stage of labor; order of preventive measures].

PMID- 14951942
TI  - [Premature bearing down as a cause of spontaneous uterine rupture].

PMID- 14951943
TI  - [Head shape in pelvic presentation].

PMID- 14951944
TI  - [Intravenous orasthin administration during the second stage with special
      reference to 100 deliveries with breech presentation].

PMID- 14951945
TI  - [Final comments on the article, Intravenous orasthin administration during the
      second stage with special reference to 100 deliveries with breech presentation].

PMID- 14951946
TI  - [Reflex contractions of the uterus by irritation of the nipple].

PMID- 14951947
TI  - [Malaria as puerperal].

PMID- 14951948
TI  - [Puerperal noninfectious wound intoxication].

PMID- 14951949
TI  - [The regulation of lactation].

PMID- 14951950
TI  - [Puncture of the abscess, followed by penicillin injection into the abscess
      cavity, in therapy of abscess-forming mastitis].

PMID- 14951951
TI  - [Rupture of a hematometra in simultaneous tubal abortion].

PMID- 14951952
TI  - [Tubal pregnancy with spontaneous sigmoid perforation and rectal abortion].

PMID- 14951953
TI  - [Diagnostic feasibility in corpus luteum retention].

PMID- 14951954
TI  - [Massive hemorrhage from a corpus luteum].

PMID- 14951955
TI  - [A contribution on pseudohermaphroditism].

PMID- 14951956
TI  - [Large recto-vaginal fistula following rape and its treatment].

PMID- 14951957
TI  - [Culdoscopy].

PMID- 14951958
TI  - [Clinical treatment and pathology of malignant uterine adenoma].

PMID- 14951959
TI  - [Cytological test for determination of ichthyol-estrogen effect].

PMID- 14951960
TI  - [Papanicolaou's technique of early detection of uterine carcinoma; clinical and
      practical application].

PMID- 14951961
TI  - [Studies on incidence and causes of climacteric and menopausal hemorrhage].

PMID- 14951962
TI  - [Applicability of colposcopy and cytodiagnosis in routine examinations for
      gynecological cancer detection].

PMID- 14951963
TI  - [Colposcopic appearance of primary cervical sarcoma and of primary luetic lesions
      of the cervix].

PMID- 14951964
TI  - [Colposcopic record forms].

PMID- 14951965
TI  - [Self-retaining vaginal speculum].

PMID- 14951966
TI  - [Study on prenatal sex determination by skin reaction following testosterone
      propionate injection].

PMID- 14951967
TI  - [Changes of existing methods of human milk dispensaries].

PMID- 14951968
TI  - [Considerations on the etiology and treatment of infant dyspepsia].

PMID- 14951969
TI  - [Diseases in newborn due to cold exposure].

PMID- 14951970
TI  - [Congenital skin defects in newborn].

PMID- 14951971
TI  - [Prenatal x-ray diagnosis of a thoracopagus].

PMID- 14951972
TI  - [Methods of artificial vagina formation].

PMID- 14951973
TI  - [Melanocytoblastoma of the vulva].

PMID- 14951974
TI  - [Tuberculosis and pregnancy].

PMID- 14951975
TI  - [The effects of protracted pentothal anesthesia on the central nervous system and
      its importance for gonadotropic function].

PMID- 14951976
TI  - [High dosage lumbar anesthesia].

PMID- 14951977
TI  - [Dolantin in obstetric analgesia].

PMID- 14951978
TI  - [Painless labor].

PMID- 14951979
TI  - [Anesthesia in cesarean section; with responses to a questionnaire].

PMID- 14951980
TI  - [An unusual case of ileus caused by pregnant uterus].

PMID- 14951981
TI  - Tuberculosis and pregnancy.

PMID- 14951982
TI  - [Cause and treatment of arrested labor in mentoposterior presentation].

PMID- 14951983
TI  - [Not Available].

PMID- 14951984
TI  - [Cyclical vascular permeability changes of the endometrium as cause of
      menstruation].

PMID- 14951985
TI  - [Hyperfolliculinism].

PMID- 14951986
TI  - [Results with Zondek's amenorrhea therapy].

PMID- 14951987
TI  - [Intraperitoneal coitus injuries].

PMID- 14951988
TI  - [Unusual intestinal injuries following perforation of the uterus].

PMID- 14951989
TI  - [Further chromatological factors and considerations].

PMID- 14951990
TI  - [Forms of membranal rupture and their definition].

PMID- 14951991
TI  - [Methyl thiouracil and labor; experimental studies].

PMID- 14951992
TI  - [Interstitial tubal pregnancy].

PMID- 14951993
TI  - [A case of unusual developmental anomaly in newborn (cephalothoracopagus)].

PMID- 14951994
TI  - [Aschheim-Zondek reaction and genital tuberculosis].

PMID- 14951995
TI  - [The role of the uterine mucosa in the transformation of progesterone into
      pregnandiol].

PMID- 14951996
TI  - [The acceleration of the menarche].

PMID- 14951997
TI  - [Surgical therapy of chronic adnexal inflammation].

PMID- 14951998
TI  - [Surgical therapy of acute adnexal tumors].

PMID- 14951999
TI  - [A case of uterine rupture in extensive damage to the uterine wall by the
      placenta].

PMID- 14952000
TI  - [Principles of controlled breeding of agricultural animals].

PMID- 14952001
TI  - [Role of the nervous system in the development of amphibians].

PMID- 14952002
TI  - [Nature of the photodynamic process].

PMID- 14952003
TI  - [Distribution of yeast in the sea].

PMID- 14952004
TI  - [Application of single dose high intensity irradiation of short duration in the
      study of dynamics of radiological effect].

PMID- 14952005
TI  - [Migration of the ovicell in swine].

PMID- 14952006
TI  - Endocardial sclerosis.

PMID- 14952007
TI  - Ineffectiveness of carob flour in infantile diarrhea.

PMID- 14952008
TI  - Lead poisoning; observations in fourteen cases.

PMID- 14952009
TI  - Values for fecal urobilinogen in childhood.

PMID- 14952010
TI  - Renal aminoaciduria; report of two cases, with studies of amino acid excretion
      patterns.

PMID- 14952011
TI  - Rare malformation of urethra as a cause of congenital obstruction of lower
      urinary tract.

PMID- 14952012
TI  - Accidental inhalation of an aureomycin capsule.

PMID- 14952013
TI  - Congenital hypoplastic anemia associated with multiple developmental defects
      (Fanconi's syndrome).

PMID- 14952014
TI  - Water intoxication; report of case in which cumulative-chloride-balance data
      aided diagnosis and therapy.

PMID- 14952015
TI  - Dermatology at the crossroads.

PMID- 14952016
TI  - Local action of steroids on senile human skin.

PMID- 14952017
TI  - Review of the psychotherapy of warts.

PMID- 14952018
TI  - Inflammatory nodosa lesions of the lower leg.

PMID- 14952019
TI  - Observations on the pharmacologic responses of Voerner's nevus anemicus.

PMID- 14952020
TI  - Mixed tumor of the lip.

PMID- 14952021
TI  - Pemphigus vegetans; a clinicopathologic correlation.

PMID- 14952022
TI  - Tumor-like keratoses; report of a case.

PMID- 14952023
TI  - Diethylstilbestrol in the treatment of senile sebaceous adenoma.

PMID- 14952024
TI  - Cicatrizing tinea capitis caused by trichophyton rubrum (trichophyton purpureum.

PMID- 14952025
TI  - Clam digger's dermatitis; schistosome dermatitis from sea water.

PMID- 14952026
TI  - Gargoylism with cutaneous manifestations.

PMID- 14952027
TI  - Ulcers of the leg in Felty's syndrome.

PMID- 14952028
TI  - Intravenous corticotropin therapy in dermatology.

PMID- 14952029
TI  - Contact dermatitis due to quotane.

PMID- 14952030
TI  - Use of attenuated or inactivated autogenous blood serum in management of
      pemphigus vulgaris; report of a case.

PMID- 14952031
TI  - Plastic diascope for dermatology.

PMID- 14952032
TI  - Alopecia areata universalis; results in one case of treatment with corticotropin
      (ACTH) and cortisone acetate intramuscularly and post-treatment observations.

PMID- 14952033
TI  - Leucoderma of penis from contact with rubber.

PMID- 14952034
TI  - Estrogens in treatment of acne vulgaris.

PMID- 14952035
TI  - Unusual distribution of chickenpox lesions.

PMID- 14952036
TI  - Lymphocytic lymphosarcoma.

PMID- 14952037
TI  - Sarcoidosis with uveitis and blindness.

PMID- 14952038
TI  - Dermatitis herpetiformis.

PMID- 14952039
TI  - Xeroderma pigmentosum.

PMID- 14952040
TI  - Case for diagnosis; lupus erythematosus?

PMID- 14952041
TI  - Lichen sclerosus et atrophicus accompanied with leucoplakia.

PMID- 14952042
TI  - Cawe for diagnosis; Duhring's disease (dermatitis herpetiformis)? Impetigo
      herpetiformis? Moniliids?

PMID- 14952043
TI  - Richard L. Sutton, M.D. 1878-1952.

PMID- 14952044
TI  - Air pollution by hydrogen sulfide in Poza Rica, Mexico; an evaluation of the
      incident of Nov. 24, 1950.

PMID- 14952045
TI  - Retention, distribution and elimination of inhaled particulates; with particular
      reference to the evaluation of radiologic risk.

PMID- 14952046
TI  - Rapid analytical method for air-pollution surveys; the determination of total
      particulates and the rapid semiquantitative spectrographic method of analysis of
      the metallic constituents in high-volume samples.

PMID- 14952047
TI  - Studies on the toxicity and skin effects of compounds used in the rubber and
      plastics industries. II. Plasticizers.

PMID- 14952048
TI  - Studies on the toxicity and skin effects of compounds used in the rubber and
      plastics industries. III. Carcinogenicity of carbon black extracts.

PMID- 14952049
TI  - Eye health evaluation and maintenance.

PMID- 14952050
TI  - Eye health evaluation and maintenance.

PMID- 14952051
TI  - Parathion exposure and cholinesterase response of Quebec apple growers.

PMID- 14952052
TI  - Pharmacological studies of radiogermanium (GE71).

PMID- 14952053
TI  - A rapid micromethod for electrometric determination of red cell cholinesterase
      activity in whole blood.

PMID- 14952054
TI  - Untoward effects on the stomach of corticotropin and cortisone.

PMID- 14952055
TI  - Peripheral vascular murmurs; mechanism of production and diagnostic significance.

PMID- 14952056
TI  - Antibiotic synergism and antagonism; review of experimental evidence.

PMID- 14952057
TI  - Erythema multiforme exudativum; study of fifteen cases.

PMID- 14952058
TI  - Paroxysmal ventricular fibrillation producing Adams-Stokes syndrome; report of
      case with review of literature.

PMID- 14952059
TI  - Genetic studies on coronary atherosclerosis developing after the age of sixty
      years.

PMID- 14952060
TI  - Role of the central nervous system in metabolism of electrolytes and water.

PMID- 14952061
TI  - Treatment of polycythemia vera with triethylene melamine; summary of thirty
      cases.

PMID- 14952062
TI  - Mandibular joint neuralgia (Costen's syndrome).

PMID- 14952063
TI  - Use of electroconvulsive therapy in a case of Addison's disease.

PMID- 14952064
TI  - Obscure fever caused by carcinoma of the kidney; a possible explanation for the
      difficulties in diagnosis.

PMID- 14952066
TI  - Review of neuropsychiatry for 1951.

PMID- 14952065
TI  - Gangrene of an extremity secondary to venous thrombosis.

PMID- 14952067
TI  - Brain of patient A. after bilateral frontal lobectomy; status of frontal-lobe
      problem.

PMID- 14952068
TI  - Pain of herpes zoster ophthalmicus.

PMID- 14952069
TI  - Effect of breath holding on arterial pressure in patients with mental and
      emotional disorders.

PMID- 14952070
TI  - Further studies on the iron content of the cerebrospinal fluid in psychoses.

PMID- 14952071
TI  - Communicating hydrocephalus from diffuse meningeal tumor; report of two cases
      with increased intracranial pressure treated by use of polyethylene tube.

PMID- 14952072
TI  - Vascular malformations of the spinal cord.

PMID- 14952073
TI  - A study of the syndromes of denial.

PMID- 14952074
TI  - Desoxycorticosterone therapy in certain psychotic cases; an interval report.

PMID- 14952075
TI  - Disturbances of vibratory sense (pallesthesia) associated with nerve root
      compression due to herniated nucleus pulposus.

PMID- 14952076
TI  - Denial of illness; its occurrence in one hundred consecutive cases of hemiplegia.

PMID- 14952077
TI  - Studies on a proteolytic enzyme system in schizophrenia.

PMID- 14952078
TI  - Analysis of cerebral control of reflex pupillary dilation in cat and monkey.

PMID- 14952079
TI  - Fusion versus nonfusion in operative treatment of protrusion of an intervertebral
      disk.

PMID- 14952080
TI  - Diencephalic dysrhythmias in patients with peptic ulcer and functional gastric
      disorders.

PMID- 14952081
TI  - Survey of newer experimental observations upon touch and pain pathways and their
      applications to clinical investigation.

PMID- 14952082
TI  - Unusual manifestations of craniopharyngioma: report of five cases.

PMID- 14952083
TI  - Discography combined with ethyl iodophenylundecylate (pantopaque) myelography.

PMID- 14952084
TI  - Relation of cerebral circulation to cerebrospinal fluid pressure: clinical
      considerations.

PMID- 14952085
TI  - Acute poliomyelitis: differential diagnosis of 409 devised diagnoses.

PMID- 14952086
TI  - Meningioma of the tuberculin sellae.

PMID- 14952087
TI  - A tumor of the optic disk associated with neurofibromatosis.

PMID- 14952088
TI  - Association of uveal nevi with skin nevi.

PMID- 14952089
TI  - Further efforts to influence x-ray cataract by chemical agents.

PMID- 14952090
TI  - Leptospiral uveitis; report of a bacteriologically verified case.

PMID- 14952091
TI  - Ocular and subcutaneous inflammatory responses to transplantation of heterologous
      tumors.

PMID- 14952092
TI  - Use of typhoid vaccine in continuous intravenous infusion in treatment of eye
      diseases.

PMID- 14952093
TI  - Ocular findings in scrub typhus.

PMID- 14952094
TI  - Dacryocystorhinostomy in infants and children.

PMID- 14952095
TI  - Ocular involvement in lymphomatous disease.

PMID- 14952096
TI  - Pathogenesis of intraocular hypertension in cases of arteriovenous aneurysm.

PMID- 14952097
TI  - A method of preventing retaining sutures from cutting into grafts.

PMID- 14952098
TI  - Ptosis clamp for holding the levator muscle during resection of the levator
      palpebrae.

PMID- 14952099
TI  - Special suturing and fixation forceps.

PMID- 14952100
TI  - Coexistence of intraocular melanoma and lymphatic leukemia.

PMID- 14952101
TI  - Use of typhoid vaccine in continuous intravenous infusion in treatment of eye
      diseases.

PMID- 14952102
TI  - The orbit; review of recent literature.

PMID- 14952103
TI  - Anoxia as a cause of endocardial fibroelastosis in infancy.

PMID- 14952104
TI  - Origin of accessory thyroid tissue from thymus IV in adult baboon.

PMID- 14952105
TI  - Morphology and pathogenesis of biliary cirrhosis.

PMID- 14952106
TI  - Kidney lesions in suckling mice following group A Coxsackie virus infection.

PMID- 14952107
TI  - Pattern of mitotic activity in oral epithelium of rabbits.

PMID- 14952108
TI  - Increasing incidence of arteriosclerotic aortic aneurysms; analysis of six
      thousand autopsies.

PMID- 14952109
TI  - Bilateral aplasia of the lung.

PMID- 14952110
TI  - Metastatic cystadenocarcinoma of ovary thirty-three years after removal of
      primary growth.

PMID- 14952111
TI  - Surgery in the Ohio Valley; its importance in the development of American
      surgery.

PMID- 14952112
TI  - Critical evaluation of jejunostomy.

PMID- 14952113
TI  - Maydi jejunostomy; technical and metabolic considerations.

PMID- 14952114
TI  - Gastric and jejunal alimentation with fine polyethylene tubes.

PMID- 14952115
TI  - Clinical studies with the electrogastrograph.

PMID- 14952116
TI  - Experimental method for an everting end-to-end anastomosis in the
      gastrointestinal tract.

PMID- 14952117
TI  - Combined abdominoendorectal resection; technical aspects and indications.

PMID- 14952118
TI  - Treatment of hemangiomas.

PMID- 14952119
TI  - Observations on etiology of esophageal varices.

PMID- 14952120
TI  - Hypertension and its relation to hepatic circulation; effects on arterial
      pressure of variations in the blood supply of the liver in normotensive,
      hypertensive and cirrhotic dogs, and in hypertensive patients with portal
      cirrhosis.

PMID- 14952121
TI  - Risk of urgent surgery in presence of myocardial infarction and angina pectoris.

PMID- 14952122
TI  - Dupuytren's contracture.

PMID- 14952123
TI  - Evaluation of three methods for finger tip injuries.

PMID- 14952124
TI  - Treated dermis as a source of reparative tissue.

PMID- 14952125
TI  - Rectus sheath grafts in vascular repair.

PMID- 14952126
TI  - Study of revascularization of blood vessel grafts by means of radioactive
      phosphorus.

PMID- 14952127
TI  - [Enzymatic activity in the course of prenatal development in man; histochemical
      study on alkaline phosphatase].

PMID- 14952128
TI  - [Thrombophlebitis states; pathogenic and clinical concepts].

PMID- 14952129
TI  - [First results with electrocorticography in a case of epilepsy].

PMID- 14952130
TI  - [Transurethral electroresection in prostato-vesical diseases].

PMID- 14952131
TI  - [Retroperitoneal insufflation and stratigraphy with special reference to direct
      radiography of the pancreas and on the possibility of production of anterior and
      posterior pneumomediastinum in adults].

PMID- 14952132
TI  - [Emergency cholecystectomy for choleperitoneum without obvious perforation of the
      biliary tract; diagnostic considerations].

PMID- 14952133
TI  - [Emergency cholecystectomy due to perforation of the peritoneum by calculus].

PMID- 14952134
TI  - The factors determining the direction of the canal for the nutrient artery in the
      long bones of mammals and birds.

PMID- 14952135
TI  - [Morphology of nerve fibers].

PMID- 14952136
TI  - [Mobilization of histiocytes at the stage of macrophages].

PMID- 14952137
TI  - [Structure of the thyroid gland; I. Structure of connective tissue].

PMID- 14952138
TI  - [Morphological findings in the pyrenophores of the ganglion cervicale uteri with
      reference to the age and function of the genital organs].

PMID- 14952139
TI  - [Experimental contribution to redox potential. VII. Normal human blood redox
      potential].

PMID- 14952140
TI  - [Loewen-Trendelenberg preparation modified by Semino-Oriol].

PMID- 14952141
TI  - [Study on antibiotic properties of Argentine lichens].

PMID- 14952142
TI  - [Experimental data on alveolar membrane].

PMID- 14952143
TI  - [Glomerular circulation in experimental asphyxia in the albino rat].

PMID- 14952144
TI  - [Cytochemical and histological demonstration of basal membranes of the kidney and
      granules of tubal secretion].

PMID- 14952145
TI  - [Physiopathology, of coughing; bronchographic study].

PMID- 14952146
TI  - [Vascular problems in the extremities].

PMID- 14952147
TI  - [Temporomandibular joint as a reflexogenic center].

PMID- 14952148
TI  - [Transplacental tuberculous infection].

PMID- 14952149
TI  - [New principles of the science of color; problem of the perception of the color
      of objects].

PMID- 14952150
TI  - [Five conferences on collagen].

PMID- 14952151
TI  - [Homogeneity of the thoracic electric field and origin of the spatial
      vectorcardiogram].

PMID- 14952152
TI  - [The electrocardiogram of the pregnant woman].

PMID- 14952153
TI  - [General electrophysiological observations on experimental ventricular extra
      systole].

PMID- 14952154
TI  - [Hemodynamic modifications following the administration of procaine amide to
      normal men].

PMID- 14952155
TI  - [Intermittent modifications in the ECG patterns of ventricular preponderance in
      congenital heart diseases].

PMID- 14952156
TI  - [A case of chronic cor pulmonale with very peculiar electrocardiograms].

PMID- 14952157
TI  - Auricular fibrillation with anomalous A-V excitation (WPW syndrome) imitating
      ventricular paroxysmal tachycardia; a case report with clinical and autopsy
      findings and critical revue of the literature.

PMID- 14952158
TI  - [Cardiovascular modifications following pneumonectomy].

PMID- 14952159
TI  - [Electrocardiographic and clinical study of the syndrome in which T I is lower
      than T III].

PMID- 14952160
TI  - [Circulation in Paget's disease of bone].

PMID- 14952161
TI  - [Contribution to the study of the double electrode with concentric contacts and
      called a "bicircular electrode"].

PMID- 14952162
TI  - [Action of procaine amide on alternations in cardiac contractility].

PMID- 14952163
TI  - [Multiple notches in the esophagus in coarctation of the aorta].

PMID- 14952164
TI  - [Arterial hypertension in surgical disorders of the kidney].

PMID- 14952165
TI  - [Arterial hypertension of urological origin].

PMID- 14952166
TI  - [Surgical treatment of tumors of the cardia].

PMID- 14952167
TI  - [Therapy of burns].

PMID- 14952168
TI  - [Water and electrolytes in the organism; review of modern concepts and
      therapeutic implications. Part three. Changes in fluid equilibrium].

PMID- 14952169
TI  - Abdominal aortography, with special reference to renal diagnosis.

PMID- 14952170
TI  - Routine cholangiography at operations for gall stones.

PMID- 14952171
TI  - Analysis of a surgical material of thyrotoxicosis.

PMID- 14952172
TI  - Diffuse papillomatosis in the rectum; report of five cases.

PMID- 14952173
TI  - Post-operative recurrence of lumbar disc herniation.

PMID- 14952174
TI  - On the effect of treatment of traumatic wounds with soap solution; an
      experimental study.

PMID- 14952175
TI  - Defecation block in cases of deep rectogenital pouch.

PMID- 14952176
TI  - Studies on the Oxford shunt.

PMID- 14952177
TI  - [Statistical study of bronchopulmonary neoplasms (100 cases)].

PMID- 14952178
TI  - [Pure pulmonary stenosis].

PMID- 14952179
TI  - [Effect of protamine sulfate on blood coagulation].

PMID- 14952180
TI  - [Application of the Kunkel method to the determination of gamma-globulines in
      hyperglobulinic serums in myelomatosis].

PMID- 14952181
TI  - [The regenerative power and reserve capacity of the liver and their value in
      surgery of the biliary tract].

PMID- 14952182
TI  - [Experimental arthritis in guinea pig].

PMID- 14952183
TI  - [Two cases of gastric cancer with polyneuritis in young adults; pathogenic
      interpretation of neurologic manifestations].

PMID- 14952184
TI  - [The danger of anticoagulant therapy].

PMID- 14952185
TI  - [Semi-automatic apparatus in microphotography].

PMID- 14952186
TI  - [Strains of enterotoxic staphylococci in alimentary poisoning].

PMID- 14952187
TI  - [Hypogonadic gynecomastia and cancer of the breast in man].

PMID- 14952188
TI  - [Extraction of urinary corticoids].

PMID- 14952189
TI  - [Isolation of virus and serologic diagnosis of influenza].

PMID- 14952190
TI  - In vitro studies on tuberculin hypersensitivity of lymph cells.

PMID- 14952191
TI  - Quantitative determination of the sebaceous secretion on the dorsal region of the
      hand during the summer period.

PMID- 14952192
TI  - Gonorrhoea and syphilis in marital partners; the route of infection.

PMID- 14952193
TI  - Repeated infections with gonorrhoea and syphilis.

PMID- 14952194
TI  - Microorganic non-bacterial urethritis in males; complications and importance.

PMID- 14952195
TI  - TRANSACTIONS of the Swedish Dermatological Society for the year 1950.

PMID- 14952196
TI  - Social and medical data of second world war's syphilis patients un Utrecht and
      its rural surroundings (Holland).

PMID- 14952197
TI  - Two cases of periarteritis nodosa.

PMID- 14952198
TI  - Case of circumscribed myxoedema with exophthalmos.

PMID- 14952199
TI  - Case of unilateral dermatitis herpetiformis in a poliomyelitis patient.

PMID- 14952200
TI  - Our experiences of vitamin E treatment (with case demonstration by G. Hagerman).

PMID- 14952201
TI  - Case of exogenetic ochronosis from carbolic acid compresses.

PMID- 14952202
TI  - The demonstration of antibodies in streptomycin eczema by the colloidon
      agglutination test.

PMID- 14952203
TI  - Antihistamine studies with bacteriologic technique.

PMID- 14952204
TI  - Attempts to cultivate virulent treponema pallidum in embryonated hen and goose
      eggs.

PMID- 14952205
TI  - Investigations into the possibility of cultivating virulent treponema pallidum in
      culture media containing phytogenic growth factors.

PMID- 14952207
TI  - TRANSACTIONS of the Danish Dermatological Society.

PMID- 14952206
TI  - TRANSACTIONS of the Norwegian Dermatological Society for the year 1949.

PMID- 14952208
TI  - Some aspects of the role of pituitary hormones in calcium metabolism. I.
      Adrenocorticotrophic hormone.

PMID- 14952209
TI  - Some aspects of the role of pituitary hormones in calcium metabolism. II. Growth
      hormone.

PMID- 14952210
TI  - Continuous intravenous administration of ACTH.

PMID- 14952211
TI  - Studies on eosinophil leucocytes in pregnancy.

PMID- 14952212
TI  - Fluorometric determination of micro amounts of oestrone-oestradiol and oestriol
      in urine.

PMID- 14952213
TI  - On the effect of electric shock on the adrenals of the rabbit.

PMID- 14952214
TI  - Effect of oestrogens on the glycogen content of the rat uterus.

PMID- 14952215
TI  - Histoquantitative studies on the effect of thyrotropin and thyroxin on the
      morphology of the thyroid gland, with special reference to standardization of the
      thyrotropic hormone; an experimental study with Guinea pigs.

PMID- 14952216
TI  - [Examination of some functions of the adrenal cortex in myxedema].

PMID- 14952217
TI  - [Hypothalamus and pituitary tumors].

PMID- 14952218
TI  - [Hepatic glycogenesial, its pituitary and cortical regulation; glycogenosis].

PMID- 14952219
TI  - [Excretion of urinary 17-ketosteroids in liver diseases].

PMID- 14952220
TI  - [Liver in diabetes in man].

PMID- 14952221
TI  - [Role of the liver in the metabolism of steroid hormones].

PMID- 14952222
TI  - [Role of the liver in the metabolism of natural estrogens].

PMID- 14952223
TI  - [The liver and the transport of fats].

PMID- 14952224
TI  - [Portal hypertension and the so-called Banti's syndrome (medical aspects)].

PMID- 14952225
TI  - [Pathological anatomy of Banti's syndrome].

PMID- 14952226
TI  - [Bioclinical aspects of the so-called Banti's syndrome; laboratory and function
      tests].

PMID- 14952227
TI  - [The so-called Banti's syndrome and portal hypertension; radiology].

PMID- 14952228
TI  - [Surgery in treatment of portal hypertension; physiopathological bases].

PMID- 14952229
TI  - [The so-called Banti's syndrome and portal hypertension; conclusions)].

PMID- 14952230
TI  - A test for red cell production.

PMID- 14952231
TI  - [Effects of vitamine K 1 on hypoprothrombinemia caused by dicumarol and on the
      acceleration factors in the rabbit with liver damage and the hepatectomized cat].

PMID- 14952232
TI  - Behaviour of factor VII and prothrombin in late pregnancy and in the newborn.

PMID- 14952233
TI  - [Pathology of reticuloses].

PMID- 14952234
TI  - [Relations of hemoblastoses to the reticuloendothelial system].

PMID- 14952235
TI  - Further observations on the anemia in kala-azar.

PMID- 14952236
TI  - [A rare finding in the sternal bone marrow in plasmocytoma].

PMID- 14952237
TI  - Present status of ACTH, cortisone, and the antimetabolites in the treatment of
      leukemia and related diseases.

PMID- 14952238
TI  - [ACTH and cortisone in therapy of non-leukemic blood dyscrasias].

PMID- 14952239
TI  - [Fluorochromation with acridinorange; a method for vital staining of blood
      cells].

PMID- 14952240
TI  - Relationship between the mean diameter of erythrocytes and the mean diameter of
      neutrophil leukocytes in human pathology.

PMID- 14952241
TI  - [The problem of eosinophile leukemia; pathogenesis of leucoses].

PMID- 14952242
TI  - [Disproteinemia in leprosy; electrophoretic study of the blood in various
      clinical forms of leprosy before and after thiosemicarbazone therapy].

PMID- 14952243
TI  - [Immunity indexes in chloromycetin therapy of brucellosis].

PMID- 14952244
TI  - [Studies on a case of rheumatoid arthritis associated with psoriasis treated with
      DOCA, DOCA and ascorbic acid, and ACTH].

PMID- 14952245
TI  - [Renal function in penicillin therapy of scarlet fever without nephrosis].

PMID- 14952246
TI  - [Relation of infection to acute leukemia; case of hemocytoblastic leukemia with
      initial lymphatic course appearing in an infectious and suppurative condition].

PMID- 14952247
TI  - [Case of dysentery].

PMID- 14952248
TI  - [Case of intestinal tuberculosis treated with isonicotinic acid hydrazide].

PMID- 14952249
TI  - [Allergic meningoencephalitis of tuberculous origin].

PMID- 14952250
TI  - [The reticuloendothelial system during and following chloramphenicol therapy].

PMID- 14952251
TI  - [Effect of roentgenotherapy of tonsillitis in a case of rheumatic peliosis].

PMID- 14952252
TI  - The place of caesarean section in obstetrics today.

PMID- 14952253
TI  - Urinary incontinence in women, excluding fistulas.

PMID- 14952255
TI  - The classification and treatment of ovarian tumours.

PMID- 14952254
TI  - Classification of ovarian tumours.

PMID- 14952256
TI  - Evaluation of results of treatment in cancer of the uterine cervix.

PMID- 14952257
TI  - Ovarian function after subtotal hysterectomy.

PMID- 14952258
TI  - Low back pain and gynaecological disease.

PMID- 14952259
TI  - An investigation into the occurrence of perinatal subdural haematoma; its
      diagnosis and treatment.

PMID- 14952260
TI  - Clinical observations on prolonged labour.

PMID- 14952261
TI  - Early ambulation after laparotomy in gynaecological cases.

PMID- 14952262
TI  - Staining of Brenner tumours by the periodate-fuchsin technique.

PMID- 14952263
TI  - Staining of polysaccharide structures in benign pseudomucinous cystadenoma of the
      ovary.

PMID- 14952264
TI  - Staining of polysaccharide structures in pseudomucinous adenocarcinoma of the
      ovary. III.

PMID- 14952265
TI  - On fluid and electrolytic balance in toxaemia of late pregnancy, in dehydration
      caused by 10 per cent salt-free macrodex.

PMID- 14952266
TI  - Pregnancy following rheumatic fever.

PMID- 14952267
TI  - Cardiac irregularities due to trichlorethylene given during labour.

PMID- 14952268
TI  - A clinical method for determination of riboflavin standard in urine after a test
      dose and the riboflavin excretion of clinically normal subjects.

PMID- 14952269
TI  - Processus alveolaris manidibulae hominis; an osteometric study.

PMID- 14952270
TI  - Some details in the histopathology of the enamel.

PMID- 14952271
TI  - [Bronchospirometry, technique and application].

PMID- 14952272
TI  - [Etiology of cancers of the respiratory tract applied to a case of cancer of the
      trachea].

PMID- 14952273
TI  - [Rotation reaction in the pigeon].

PMID- 14952274
TI  - [Auditory fatigue].

PMID- 14952275
TI  - [Protection against occupational deafness; role of vitamin A].

PMID- 14952277
TI  - [Some personal experiences concerning fenestration].

PMID- 14952276
TI  - [Pathognomy of the radio-otoscopic jugular foramen syndrome].

PMID- 14952278
TI  - [Rare endocranial complications of otitis].

PMID- 14952279
TI  - [Hemifacial restoration].

PMID- 14952280
TI  - [Restoration of the nose].

PMID- 14952281
TI  - [The so-called latero-pharyngeal fibromas].

PMID- 14952282
TI  - ELIZABETH Dingemanse.

PMID- 14952283
TI  - SIR Charles Scott Sherrington.

PMID- 14952284
TI  - Attempts to construct an oxygenator for temporary replacement of the human lung.

PMID- 14952285
TI  - Polyuria and sugar excretion in alloxan diabetic rats.

PMID- 14952286
TI  - Studies on the action of synephrine, neosynephrine, and quinidine on cardiac
      fibrillation.

PMID- 14952287
TI  - Studies on the action of papaverine and perparine on cardiac fibrillation.

PMID- 14952288
TI  - Influence of tetra-ethyl-thiuramdisulphide (T.T.S.) on the metabolism of quinine
      in vivo.

PMID- 14952289
TI  - Influence of tetra-ethyl-thiuramdisulphide (T.T.S.) on the in vivo actions of
      quinine hydrochloride.

PMID- 14952290
TI  - Synthesis of fat from carbohydrate in thiamine deficiency.

PMID- 14952291
TI  - DUTCH Society of Physiology and Pharmacology.

PMID- 14952292
TI  - Comparative efficiency of different methods of treating acetonaemia in milch
      cows, relatively to its etiology.

PMID- 14952293
TI  - The increase of thyroid activity and the decrease of metabolism by administration
      of methyl-thiouracil and protein.

PMID- 14952294
TI  - Investigations on the glycolytic enzyme system of calcifying bones.

PMID- 14952295
TI  - DUTCH Society for Endocrinology.

PMID- 14952296
TI  - Regulation of spermatogenesis in Rana.

PMID- 14952297
TI  - The effect of A.C.T.H. in a patient suffering from Simmonds-Sheehan disease.

PMID- 14952298
TI  - The development of the mammary gland in the adult male rat and of cystic
      mastopathia following treatment with steroids.

PMID- 14952299
TI  - Effect of chorionic gonadotropic hormone in a case of adiposo-genital dystrophy
      with hypometabolism and mental retardation.

PMID- 14952300
TI  - Cystic ovaries.

PMID- 14952301
TI  - [Marceli Nencki (fiftieth anniversary of his death)].

PMID- 14952302
TI  - [Three principles of Pavlov's theory of reflex].

PMID- 14952303
TI  - [Dynamics of cortical processes].

PMID- 14952304
TI  - [Conditioned reflex of motor analysor; mechanism of conditioned motor reaction].

PMID- 14952305
TI  - [Conditioned reflex of motor analysor; inhibitory after-effect of conditioned
      reflex of motor analysor].

PMID- 14952306
TI  - [Physiological mechanism of active rest].

PMID- 14952307
TI  - [Effect of the position of the body on function of circulatory and respiratory
      systems].

PMID- 14952308
TI  - [Respiratory changes occurring in systematically repeated trial to breathe in a
      closed space].

PMID- 14952309
TI  - [Oxygen consumption in myocardial tissue suspension].

PMID- 14952310
TI  - [Effect of lower alcohols on oxygen consumption in suspension of myocardial
      tissue].

PMID- 14952311
TI  - [Johannes Purkinje].

PMID- 14952312
TI  - Application of 42K labelled red corpuscles in blood volume measurements.

PMID- 14952313
TI  - Studies on the regulation of respiration in acute hypoxia; with a appendix on
      respiratory control during prolonged hypoxia.

PMID- 14952314
TI  - The in vitro formation of carbon monoxide in blood.

PMID- 14952315
TI  - The effect of adrenaline on the contraction of the human heart under normal
      circulatory conditions.

PMID- 14952316
TI  - The influence of the autonomic nervous system on the contraction of the human
      heart under normal circulatory conditions.

PMID- 14952317
TI  - The influence of electrolytes on the rate of viscosity drop in ATP-actomyosin
      mixtures.

PMID- 14952318
TI  - Further investigations on the phosphorus and nucleotide uptake of actomyosin.

PMID- 14952319
TI  - [The pituitary and diseases of the skeleton].

PMID- 14952320
TI  - [Auric nephrosis].

PMID- 14952321
TI  - [Surgery of the stiff shoulder].

PMID- 14952322
TI  - Hereditary joint disease; observations on Heberden's nodes, gout and ankylosing
      spondylitis.

PMID- 14952323
TI  - [Some aspect of antirheumatismal tuberculinotherapy].

PMID- 14952324
TI  - [Triple dorsal calcification of the nucleus pulposus].

PMID- 14952325
TI  - [Thermal cure and adrenal cortex stimulation].

PMID- 14952327
TI  - Auscultation of the orbit as a diagnostic method in unilateral exophthalmos.

PMID- 14952326
TI  - Observations on the Eustachian tube.

PMID- 14952328
TI  - Formation of neuromeres in homo.

PMID- 14952329
TI  - Staining of masked lipids in the capsular epithelium of the eye lens.

PMID- 14952330
TI  - Functional thickness variations of human articular cartilage.

PMID- 14952331
TI  - The efficacy of artificial respiration tested under narkotal-curare anaesthesia.

PMID- 14952332
TI  - [An auxiliary method for determination of degrees of polyploidy in mammals].

PMID- 14952333
TI  - Muscle changes in connection with rheumatoid arthritis and osteo-arthritis; a
      roentgenological study of the extremital fat.

PMID- 14952334
TI  - Notes on the proliferation processes in the neuromeres in vertebrate embryos.

PMID- 14952335
TI  - Anomalous vena cava cranialis sinistra; report of a unilateral case.

PMID- 14952336
TI  - [Cavernostomy (Maurer's drainage) in treatment of pulmonary tuberculosis].

PMID- 14952337
TI  - [Clinical lessons in tuberculosis statistics for 1948].

PMID- 14952338
TI  - [First results of the hemagglutination reaction of Middlebrook-Dubos].

PMID- 14952339
TI  - [Treatment of cavities by a complete rest and antibiotics; results of sanatorium
      and free cure].

PMID- 14952340
TI  - [The effect of pulmonary elasticity on heart movements].

PMID- 14952341
TI  - On the reliability of the reading of photofluorograms and value of dual reading.

PMID- 14952342
TI  - Passive transfer of tuberculin hypersensitivity by viable lymphocytes from the
      thoracic duct.

PMID- 14952343
TI  - The results of treatment of pulmonary tuberculosis with combined administration
      of PAS and streptomycin.

PMID- 14952344
TI  - Results in treating tuberculous empyemata with para-aminosalicylic acid or with
      combined administration of para-aminosalicylic acid and streptomycin.

PMID- 14952345
TI  - [The leucocyte blood picture during streptomycin therapy of pulmonary
      tuberculosis].

PMID- 14952346
TI  - The nature of the resistance of tubercle bacilli to streptomycin.

PMID- 14952347
TI  - The growth of tubercle bacilli at sub-optimum temperatures.

PMID- 14952348
TI  - The preservation of BCG by freeze-drying.

PMID- 14952349
TI  - Reflections concerning some cases of tuberculous meningitis.

PMID- 14952350
TI  - Erythema nodosum and subsequent tuberculosis; a follow-up study of 575 cases.

PMID- 14952351
TI  - Present views concerning collapse therapy of pulmonary tuberculosis.

PMID- 14952353
TI  - The epizootic of tuberculosis among the Gias in Bahia.

PMID- 14952352
TI  - On vaccination with vole bacilli.

PMID- 14952355
TI  - A survey of tuberculosis of the kidney in relation to tuberculosis in general.

PMID- 14952354
TI  - Laboratory control of B.C.G. vaccine with special reference to the value of some
      current methods of examination.

PMID- 14952356
TI  - [Benign cutaneous lymphadenosis].

PMID- 14952357
TI  - [Contribution to the study of necrobiosis lipoidica].

PMID- 14952358
TI  - [So-called giant cell sarcoma of the skin; two cases].

PMID- 14952359
TI  - [Virulence of herpes virus preserved in glycerin].

PMID- 14952360
TI  - [Experimental immunity to herpes].

PMID- 14952361
TI  - [In Memorian of Doctor Miguel Fernandez Criado].

PMID- 14952362
TI  - [Case of a tuberculous chancre of the skin].

PMID- 14952363
TI  - [Granuloma annulare].

PMID- 14952364
TI  - [Preliminary note to the study of superficial nycoses in Galecia].

PMID- 14952365
TI  - [A typical case of tuberculous lupus].

PMID- 14952366
TI  - [Case of erythema annulare centrifugum].

PMID- 14952367
TI  - [Treatment of gonococcal infections with a combination of chloramphenicol,
      sulfathiazole and antihistaminics].

PMID- 14952368
TI  - [Case of leprosy].

PMID- 14952369
TI  - [First impressions on chloramphenicol in venereological therapy].

PMID- 14952370
TI  - [Contribution to the study of chronic porphyria].

PMID- 14952371
TI  - [Perineoscrotal elephantiasis].

PMID- 14952372
TI  - [Contribution to the study of basal metabolism in pelada].

PMID- 14952373
TI  - Advances in the treatment of bacterial meningitis.

PMID- 14952374
TI  - The nephrotic syndrome in children.

PMID- 14952375
TI  - The relation of vitamin K deficiency to hemorrhagic disease of the newborn.

PMID- 14952376
TI  - Angiocardiographic studies in children.

PMID- 14952377
TI  - Iron metabolism in infants and children; serum iron and iron-binding protein
      diagnostic and therapeutic implications.

PMID- 14952378
TI  - BCG vaccination.

PMID- 14952379
TI  - [Constants, test individualities].

PMID- 14952380
TI  - [Epituberculosis; perforation of caseous tuberculous lymph nodes into the
      bronchial lumen].

PMID- 14952381
TI  - [Diminution of operative blood loss by artificial hypotension].

PMID- 14952383
TI  - [Esophageal perforation].

PMID- 14952382
TI  - [Congenital atresia of the duodenum].

PMID- 14952384
TI  - [Purpura Schoenlein-Henoch].

PMID- 14952385
TI  - [A new device for intra-arterial transfusion].

PMID- 14952386
TI  - [Oxyuris therapy with helmetina, an anthelmintic containing phenothiazine and
      chocolate].

PMID- 14952387
TI  - [Hormones as remedy].

PMID- 14952388
TI  - [Streptomycin therapy of meningeal tuberculosis in infants; results and
      limitations].

PMID- 14952389
TI  - [Trends of medical therapy of peptic ulcer].

PMID- 14952390
TI  - [Experience with Chediak's quick serological test of syphilis using a stabilized
      diluted extract according to the Chediak method].

PMID- 14952391
TI  - [Caisson-disease].

PMID- 14952392
TI  - [Ectesia of trachea simulating pulmonary cavitation; bronchology of pulmonary
      tuberculosis].

PMID- 14952393
TI  - [Epidemiologic observations during the tularemia-epidemy in Schleswig-Holstein
      1950-51].

PMID- 14952394
TI  - [Biochemistry and physiology of iodine metabolism].

PMID- 14952395
TI  - [Surgical therapy of fractures and penicillin].

PMID- 14952396
TI  - [Trends of medical therapy of peptic ulcer. II. New viewpoints on improved
      therapeutic results].

PMID- 14952397
TI  - [Tolerance of intravenous iron application].

PMID- 14952398
TI  - [Syphilis a reason for refusal or withdrawal of the drivers license].

PMID- 14952399
TI  - [Diagnosis and therapy of hearing disorders and their improvement with hearing
      aids].

PMID- 14952400
TI  - [Poliomyelitis and Coxsackie virus infection; a case of fatal poliomyelitis with
      isolation of Coxsackie virus].

PMID- 14952401
TI  - [Reduced glutathione in blood preserve].

PMID- 14952402
TI  - [Aspects on the removal of pigmented nevus].

PMID- 14952403
TI  - [Therapy of periarthritis humero-scapularis].

PMID- 14952404
TI  - [The modern clinician].

PMID- 14952405
TI  - [Vvedenskii's theory and its significance in physiology and medicine].

PMID- 14952406
TI  - [Method of decrease of the rate of gynecological diseases and associated working
      incapacity].

PMID- 14952407
TI  - [Modification of reactivity of the organism to placental proteins in vitamin C
      deficiency].

PMID- 14952408
TI  - [Application of vaginal examination in labor].

PMID- 14952409
TI  - [Cesarean section in contemporary gynecology].

PMID- 14952410
TI  - [Immediate and remote results of cesarean section].

PMID- 14952411
TI  - [Intracranial injuries in newborn].

PMID- 14952412
TI  - [Control of initial loss of weight in newborn by hemoclyster with retroplacental
      blood].

PMID- 14952413
TI  - [Pathohistological changes in the female genitalia in acute infectious diseases].

PMID- 14952414
TI  - [Genitourinary and genitointestinal fistulas and their therapy].

PMID- 14952415
TI  - [Treatment of deep and high vesicocervical fistulas].

PMID- 14952416
TI  - [Therapy of fistulas according to Buiko's method].

PMID- 14952417
TI  - [Therapy of postoperative genitourinary fistulas].

PMID- 14952418
TI  - [Pathological human fertilized ovum].

PMID- 14952419
TI  - [Condition of the placental stage of labor with complications].

PMID- 14952420
TI  - [Utilization of Popov's operation in surgery of rectovaginal fistula and
      formation of artificial vagina].

PMID- 14952421
TI  - [Chronic uterine fistula with infiltration of lochia into the abdominal cavity].

PMID- 14952422
TI  - [Delivery of quintuplets].

PMID- 14952423
TI  - [Delivery of quadruplets].

PMID- 14952424
TI  - [First Russian works on female sex hormones and their hormones].

PMID- 14952425
TI  - [Condition of obstetrics].

PMID- 14952426
TI  - [The disturbances of blood lipo-proteins and their correction by heparin in
      atherosclerosis].

PMID- 14952427
TI  - [The diagnosis and present treatment of pulmonary actinomycosis].

PMID- 14952428
TI  - [A new test in physiopathology; reticulo-endothelial index].

PMID- 14952429
TI  - [Proposition of a simplified technique for the execution of carrying out Sandor's
      reticulo-endothelial index].

PMID- 14952430
TI  - [Generalized tetanus treated with success by sero-anatoxitherapy, penicillin
      therapy and curarization].

PMID- 14952431
TI  - [Crenotherapic observation station of Hamman Guergour].

PMID- 14952432
TI  - [The electrocardiographic syndrome post-tachycardia].

PMID- 14952433
TI  - [The remarkable effect of heparin in two cases of asystole].

PMID- 14952434
TI  - [Polynuclear eosinophils].

PMID- 14952435
TI  - [Two recent cases of primary bronchial tuberculosis simulating cancer].

PMID- 14952436
TI  - [Brutal reactivation of rheumatoid articular arthritis under the effect of
      cortisone after successful salicylate treatment].

PMID- 14952437
TI  - [Large amebic abscess of the liver treated and cured by combined emetine
      aureomycin and drainage].

PMID- 14952438
TI  - A method for recording spatial vectorcardiograms.

PMID- 14952439
TI  - The spatial vectorcardiogram during the first decade of life.

PMID- 14952440
TI  - Levocardia.

PMID- 14952441
TI  - Uncomplicated isolated dextrocardia (dextroversio cordis type).

PMID- 14952442
TI  - Chronic constrictive pericarditis: further consideration of the pathologic
      physiology of the disease.

PMID- 14952444
TI  - Dissociation with interference in the presence of 2:1 atrioventricular block.

PMID- 14952443
TI  - Studies on the mechanism of ventricular activity. III. Contraction of the
      ventricles in experimental bundle branch block.

PMID- 14952445
TI  - The dual displacement and velocity ballistocardiograph apparatus.

PMID- 14952446
TI  - Ballistocardiographic response to nitroglycerin in coronary artery disease.

PMID- 14952447
TI  - The fusion frequency of flicker in hypertension; a study of its application the
      estimation of hypertensive cardiovascular disease.

PMID- 14952448
TI  - Drug effects in Wolff-Parkinson-White syndrome.

PMID- 14952449
TI  - Clinical diuretic studies on three new mercurial compounds.

PMID- 14952450
TI  - A mannikin to simplify the teaching of congenital heart disease.

PMID- 14952451
TI  - Schistosomal heart disease: bilharzic cor pulmonale.

PMID- 14952452
TI  - Necrosis of a cardiac papillary muscle following infarction with incomplete
      rupture.

PMID- 14952453
TI  - Ballistocardiographic findings in a case of pulsus alternans.

PMID- 14952454
TI  - Boeck's sarcoid with unusual cardiac configuration and electrocardiographic
      changes.

PMID- 14952455
TI  - Studies in mitral stenosis. II. Observations on incidence of active rheumatic
      carditis in left auricular appendages resected at operation for mitral stenosis.

PMID- 14952456
TI  - Rheumatic heart disease with calcification of the left auricle; report of two
      cases with review of the literature.

PMID- 14952457
TI  - Congenital pulmonic stenosis with open foramen ovale in infancy; report of five
      proved cases.

PMID- 14952458
TI  - Patent ductus arteriosus with partial reversal of the shunt; a study of two
      cases.

PMID- 14952459
TI  - Modification of a vector model to provide accurate recording of mean vector
      positions in three planes of space.

PMID- 14952460
TI  - A geometric model for determining the direction of mean spatial vectors.

PMID- 14952461
TI  - A simple technique for registering the direction of rotation of
      vectorcardiographic loops.

PMID- 14952462
TI  - The depressing effect of inositol on serum cholesterol and lipid phosphorus in
      hypercholesteremic myocardial infarct survivors.

PMID- 14952463
TI  - Mephentermine: an effective pressor amine; clinical and laboratory observations.

PMID- 14952464
TI  - Shock accompanying myocardial infarction: treatment with pressor amines amines.

PMID- 14952465
TI  - Cardiac arrhythmias following the use of large doses of central nervous system
      stimulants.

PMID- 14952466
TI  - The action of procaine amide in complete heart block.

PMID- 14952467
TI  - A modification of the fluorescein circulation time.

PMID- 14952468
TI  - Penetration into pericardial cavity during cardiac catheterization.

PMID- 14952469
TI  - Dysphagia lusoria: an unusual case.

PMID- 14952470
TI  - The present status of electrokymography; a review.

PMID- 14952471
TI  - The symbolic bird in medieval and renaissance art.

PMID- 14952472
TI  - Asherah of Ugarit.

PMID- 14952473
TI  - Othello's obsessions.

PMID- 14952474
TI  - Notes on the berit in two dreams.

PMID- 14952475
TI  - The bull-fight as a religious ritual.

PMID- 14952477
TI  - The mobility of pneumoconiotic deposits.

PMID- 14952476
TI  - The total personality in creative therapy.

PMID- 14952478
TI  - Evaluation of serum potassium levels.

PMID- 14952479
TI  - Parenchymal calcification of the kidneys in patients with duodenal ulcer.

PMID- 14952480
TI  - Effect of adrenocorticotropic hormone (ACTH) on serum amylase activity and
      carbohydrate metabolism.

PMID- 14952482
TI  - A practical method for storing organs in cases of fatal poisoning.

PMID- 14952481
TI  - A survey of thyroid glands obtained at autopsy in a so-called goiter area.

PMID- 14952483
TI  - Cerebral and visceral inclusion disease of infancy.

PMID- 14952484
TI  - Presence of Enterobius (Oxyuris) vermicularis in the ovary.

PMID- 14952485
TI  - Clinicopathological conference: chorionepithelioma.

PMID- 14952486
TI  - Ethyl alcohol in blood and urine; a simple photometric method for its forensic
      determination.

PMID- 14952487
TI  - Dubos' medium with albumin for yeast-phase growth of Histoplasma capsulatum.

PMID- 14952488
TI  - Further modifications of the Friedman test.

PMID- 14952489
TI  - Decalcification of bone with trifluoroacetic acid.

PMID- 14952490
TI  - Smear method for rapid diagnosis of neurosurgical material.

PMID- 14952491
TI  - Polyethylene tubing for collecting increased amount of blood serum for
      microchemical tests.

PMID- 14952492
TI  - Hepatic tests in preterminal hepatic insufficiency.

PMID- 14952493
TI  - Differential diagnosis of hepatitis and liver cirrhosis by means of
      cholecystography.

PMID- 14952494
TI  - Effect of sodium carboxymethylcellulose on the blood cells.

PMID- 14952495
TI  - The surgical treatment of portal hypertension.

PMID- 14952496
TI  - In situ hydrogen ion measurements of the mouth, esophagus and stomach in newborn
      infants.

PMID- 14952497
TI  - Bentyl hydrochloride successful administration of a parasympatholytic
      antispasmodic in glaucoma patients.

PMID- 14952499
TI  - Immediate ambulation.

PMID- 14952498
TI  - Pre-and post-surgical use of intravenous glucose infusion with aqueous multi
      vitamin complement: report of 137 cases.

PMID- 14952500
TI  - The hydriodide of diethylaminoethylester penicillin-G neopenil, III. Unusually
      high penicillin concentrations in cerebrospinal fluid following intramuscular
      administration.

PMID- 14952501
TI  - Vitamin B12 in the treatment of viral hepatitis; a preliminary report.

PMID- 14952502
TI  - The relationship of biliary tract disorders to diabetes mellitus.

PMID- 14952503
TI  - Platelet agglutination by an abnormal plasma factor in thrombocytopenic purpura
      associated with quinidine ingestion.

PMID- 14952504
TI  - The use of amphetamine in barbiturate poisoning.

PMID- 14952505
TI  - Hypertension as a reaction pattern to stress; correlation of circulatory
      hemodynamics with changes in the attitude and emotional state.

PMID- 14952506
TI  - The vasodilator effects of intravenous procaine in patients with ischemic
      extremities.

PMID- 14952507
TI  - Evaluation of paveril in angina pectoris.

PMID- 14952508
TI  - Management of khellin toxicity; effects of dosage and purification.

PMID- 14952509
TI  - The relationship of chronic peptic ulcer to coronary thrombosis.

PMID- 14952510
TI  - On the relation between the site of valvular involvement in endocarditis and the
      blood pressure resting on the valve.

PMID- 14952511
TI  - The benefit of respiratory exercises in the emphysematous patient.

PMID- 14952512
TI  - Comparative study of ascorbic acid levels in gastric secretion, blood, urine and
      saliva. II. Saturation studies.

PMID- 14952513
TI  - Experimental rheumatic carditis, periarteritis nodosa and glomerulonephritis.

PMID- 14952514
TI  - Premature birth as a problem of human populations.

PMID- 14952515
TI  - A twenty five year evaluation of the treatment of carcinoma of the cervix with
      irradiation.

PMID- 14952516
TI  - An evaluation of intravenous pituitrin.

PMID- 14952517
TI  - The epithelial changes in the fetal cervix, including the role of the reserve
      cell.

PMID- 14952518
TI  - Specific hypertensive disease of pregnancy; factors affecting infant mortality.

PMID- 14952519
TI  - Papilloma of the cervix.

PMID- 14952520
TI  - Observations upon the role of the sex hormones in development of bony pelvic
      conformation.

PMID- 14952521
TI  - Scars of the pregnant and nonpregnant uterus. I. Histologic comparison of scars
      two weeks postoperatively.

PMID- 14952522
TI  - The hepatorenal syndrome complicating pregnancy.

PMID- 14952523
TI  - Endoscopy in gynecology.

PMID- 14952524
TI  - Problems and difficulties in the clinical teaching of obstetrics and gynecology
      as of today.

PMID- 14952525
TI  - Coitus and late pregnancy, delivery, and the puerperium; a preliminary report.

PMID- 14952526
TI  - Variation in size and weight of twins of monochorial pregnancies.

PMID- 14952527
TI  - Arteriectasia of the uterine artery.

PMID- 14952528
TI  - Ovarian pregnancy; case report with discussion of controversial issues in the
      literature.

PMID- 14952529
TI  - Uterodynamics in pregnancy and labor, with special reference to calcium and
      quinine.

PMID- 14952530
TI  - Studies on Rh. I. Evaluation of antihuman globulin serum in the hemolytic disease
      of the newborn.

PMID- 14952531
TI  - Classification of forceps operations according to uniform radiological and
      clinical criteria.

PMID- 14952532
TI  - Statistics of births in the United States.

PMID- 14952533
TI  - Leptotrichia (Leptothrix) vaginalis.

PMID- 14952534
TI  - An evaluation of various methods of vaginal asepsis.

PMID- 14952535
TI  - The balanced mixture for terminal anesthesia in the parturient; preliminary
      report.

PMID- 14952536
TI  - A test for lactation success; a preliminary report.

PMID- 14952537
TI  - Residual carcinoma in the vaginal cuff after radical hysterectomy with bilateral
      pelvic lymph node dissection.

PMID- 14952538
TI  - Sustained contractions of the gravid uterus during spinal anesthesia.

PMID- 14952539
TI  - Repair of enterocele with preservation of the vagina.

PMID- 14952540
TI  - A proposed classification for cases of cancer of the cervix treated by surgery.

PMID- 14952541
TI  - The use of menadione bisulfite and ascorbic acid in the treatment of nausea and
      vomiting of pregnancy; a preliminary report.

PMID- 14952542
TI  - The management of the third stage of labor employing a combination of pitocin and
      methylergonovine (methergine).

PMID- 14952543
TI  - Osteogenic sarcoma of the ovary.

PMID- 14952544
TI  - Spontaneous rupture of the uterus resulting from placenta accreta.

PMID- 14952545
TI  - A unilateral ovary with polycystic disease.

PMID- 14952546
TI  - Retroperitoneal hematoma during pregnancy.

PMID- 14952547
TI  - Postabortal sepsis treated with surgery and antibiotic therapy.

PMID- 14952548
TI  - Notes on the 8 and 24 hour Frank Berman pregnancy test.

PMID- 14952549
TI  - Bilateral ectopic gestation.

PMID- 14952550
TI  - Squamous-cell carcinoma developing from a marsupialized dermoid of the ovary.

PMID- 14952551
TI  - Primary cervical choriocarcinoma.

PMID- 14952552
TI  - Clinical pointers in strabismus orthoptics.

PMID- 14952553
TI  - The effect of aniseikonia on the amplitude of vertical divergence.

PMID- 14952554
TI  - Suggestions for a new fee structure in optometry.

PMID- 14952555
TI  - A study of the relationship between lateral phoria and age.

PMID- 14952556
TI  - Compendium on eye protective devices.

PMID- 14952558
TI  - The common-sense horopter.

PMID- 14952557
TI  - The changes in refraction between the ages of 5 and 14; theoretical and practical
      considerations.

PMID- 14952559
TI  - Suggestions for a new fee structure in optometry.

PMID- 14952560
TI  - The A. Ph. A. and its influence.

PMID- 14952561
TI  - Pharmaceutical manufacturers' plans.

PMID- 14952562
TI  - Inaugural address of the incoming president of the A.M.A.

PMID- 14952563
TI  - Are pharmacy colleges meeting the needs of the profession and industry?

PMID- 14952564
TI  - The mastoid process in the chimpanzee and gorilla.

PMID- 14952565
TI  - Missing teeth with special reference to the population of Tristan da Cunha.

PMID- 14952566
TI  - Physical growth and development.

PMID- 14952567
TI  - Applied physical anthropology.

PMID- 14952568
TI  - Air Force anthropology in 1950.

PMID- 14952569
TI  - Applied anthropometry of the hand.

PMID- 14952570
TI  - Are certain blood dyscrasias an effect of racial mixture?

PMID- 14952571
TI  - Dial spreading caliper.

PMID- 14952573
TI  - PROCEEDINGS of the twenty-first annual meeting of the American Association of
      Physical Anthropologists.

PMID- 14952572
TI  - Viking fund medallist for 1951.

PMID- 14952574
TI  - SYMPOSIUM on the back.

PMID- 14952575
TI  - AMERICAN Association of Physical Anthropologists; members.

PMID- 14952576
TI  - Diagnosis and treatment of amebiasis.

PMID- 14952577
TI  - Anesthesia for anorectal surgery: a status evaluation.

PMID- 14952578
TI  - Anorectal complications; the relationship of complications encountered in
      obstetrics and gynecology.

PMID- 14952579
TI  - Bowel management in postoperative care of anorectal wounds.

PMID- 14952580
TI  - Preventive proctology.

PMID- 14952581
TI  - Diagnostic problems in carcinoma of the colon; a presentation of three cases.

PMID- 14952583
TI  - Fistulas.

PMID- 14952582
TI  - Anorectal surgery; preoperative and postoperative care.

PMID- 14952584
TI  - CATHOLIC Church and psychoanalysis.

PMID- 14952585
TI  - The training of non-medical cooperative psychotherapists by multiple
      psychotherapy.

PMID- 14952586
TI  - Psychosomatic proctology.

PMID- 14952587
TI  - Some psychological processes in supervision of therapists.

PMID- 14952588
TI  - Evaluation of psychotherapy with modified Rorschach techniques.

PMID- 14952589
TI  - The diagnostic importance of early recollections.

PMID- 14952590
TI  - The Ishmael complex.

PMID- 14952591
TI  - The dissocial superego.

PMID- 14952592
TI  - Sexual development in Israeli adolescents.

PMID- 14952593
TI  - The concept of normality.

PMID- 14952594
TI  - Progress of American industrial medicine in the first half of the twentieth
      century.

PMID- 14952595
TI  - Prevalence of pleuropneumonia-like organisms and the evaluation of media and
      methods for their isolation from clinical material.

PMID- 14952596
TI  - Comparison of histoplasmin sensitivity rates among human beings and animals in
      Boone County, Missouri.

PMID- 14952597
TI  - Isolation of histoplasma capsulatum from soil.

PMID- 14952598
TI  - The engineering approach to cleaner air for the community.

PMID- 14952599
TI  - Methods of predicting total cases of poliomyelitis during epidemic periods.

PMID- 14952600
TI  - Temporary disability insurance.

PMID- 14952601
TI  - Workmen's compensation and rehabilitation.

PMID- 14952602
TI  - Food habits of Maine school children.

PMID- 14952603
TI  - A tab system for use in the follow-up of health examinations.

PMID- 14952604
TI  - The need for continuous dental treatment in elementary school children.

PMID- 14952605
TI  - Relationship between federal, state, and local food sanitation programs.

PMID- 14952606
TI  - A comparative study of cancer mortality in England and the United States.

PMID- 14952607
TI  - NURSES unite for service.

PMID- 14952608
TI  - RESEARCH program of the U.S. Public Health Service.

PMID- 14952609
TI  - QUACKERY in the field of nutrition.

PMID- 14952611
TI  - Chest radioautography.

PMID- 14952610
TI  - EIGHTIETH annual meeting American Public Health Association Cleveland, Ohio,
      October 20-24, 1952.

PMID- 14952612
TI  - Telepaque: a new cholecystographic medium with improved visualization of the bile
      ducts.

PMID- 14952613
TI  - Clinical and roentgenological manifestations of the Klippel-Feil syndrome
      (congenital fusion of the cervical vertebrae, brevicollis); report of eight
      additional cases and review of the literature.

PMID- 14952614
TI  - The roentgen diagnosis of dextroposition of the aorta.

PMID- 14952615
TI  - Retroperitoneal pneumography by injection of oxygen into the presacral space.

PMID- 14952616
TI  - The significance of intra-abdominal calcification in the newborn infant.

PMID- 14952617
TI  - Volvulus of the cecum.

PMID- 14952618
TI  - Arteriographic visualization of the choroid plexus of the temporal horn of the
      lateral ventricle.

PMID- 14952619
TI  - The use of fusible metal as a radiopaque contrast medium and in the preparation
      of anatomical castings.

PMID- 14952620
TI  - The use of radioactive colloidal gold (Au198) in pleural effusions and ascites
      associated with malignancy.

PMID- 14952621
TI  - Diagnostic use of radioactive isotopes.

PMID- 14952622
TI  - Rotational scanning of breast malignancies with supervoltage radiation.

PMID- 14952623
TI  - Roentgen therapy of the anginal syndrome.

PMID- 14952624
TI  - Multicentric mammary cancer developing in previously irradiated breast.

PMID- 14952625
TI  - A method of rapid chest photofluorography.

PMID- 14952626
TI  - UNTOWARD effects of cerebral angiography.

PMID- 14952627
TI  - Davis Spangler 1892-1952.

PMID- 14952628
TI  - Julius B. Wantz 1874-1952.

PMID- 14952630
TI  - MINES bureau shows way to curb operating room explosions.

PMID- 14952629
TI  - B. Swayne Putts 1882-1952.

PMID- 14952631
TI  - Needle biopsy of the liver; an analysis of 308 cases.

PMID- 14952632
TI  - Cardiac arrest during surgical procedures; review of the literature with a report
      of six cases.

PMID- 14952633
TI  - Changes in the vertebra caused by ruptured intervertebral discs; observations on
      their formation and treatment.

PMID- 14952634
TI  - Syndrome of the degenerated intervertebral disc.

PMID- 14952635
TI  - Evaluation of the results of partial gastrectomy for the treatment of duodenal
      ulcer.

PMID- 14952636
TI  - Abdominal incisions; present status in the United States.

PMID- 14952637
TI  - Experimental studies using tantalum mesh as a full-thickness abdominal wall
      prosthesis.

PMID- 14952638
TI  - Peripheral thrombosis treated with alpha tocopherol (vitamin E).

PMID- 14952639
TI  - Effects of ACTH and cortisone on refrigerated homografts in the experimental
      animal.

PMID- 14952640
TI  - Management of varicose veins and their related problems.

PMID- 14952641
TI  - Lumbar sympathectomy in peripheral vascular diseases.

PMID- 14952642
TI  - Diseases of the urachus; with three illustrative case reports.

PMID- 14952643
TI  - Postmortem cesarean section; surgical and legal aspects.

PMID- 14952644
TI  - Chronic appendicitis or painful ovary.

PMID- 14952645
TI  - Abortion.

PMID- 14952646
TI  - Intra-abdominal choledochography; preliminary report of a method of detecting
      stones in the common bile duct.

PMID- 14952647
TI  - Abdominal drainage in cirrhosis by use of glass button.

PMID- 14952648
TI  - Cecostomy.

PMID- 14952649
TI  - The tube bundle surgical drain.

PMID- 14952650
TI  - Adrenal cortex tumors.

PMID- 14952651
TI  - Subcostosternal diaphragmatic hernia.

PMID- 14952652
TI  - Trichinosis complicating pregnancy.

PMID- 14952653
TI  - Urachal cysts and their complications.

PMID- 14952654
TI  - Pelvic phantom tumors.

PMID- 14952655
TI  - Treatment of soft part tumors.

PMID- 14952656
TI  - Rupture of the intervertebral disc in industry; further observations on the end
      results.

PMID- 14952657
TI  - Replacement reconstruction of the hip.

PMID- 14952658
TI  - The bladder and ureter in gynecology.

PMID- 14952659
TI  - Hashimoto's disease (struma lymphomatosa); a familial incidence of three cases.

PMID- 14952660
TI  - Retroperitoneal rupture of the duodenum in non-penetrating abdominal trauma.

PMID- 14952661
TI  - Surgical considerations in removal of renal and ureteral calculi, with special
      emphasis on removal of staghorn calculi.

PMID- 14952662
TI  - Surgery of the esophagus through the right chest.

PMID- 14952663
TI  - Cancer of the breast.

PMID- 14952664
TI  - Ischemic fibrosis of the lower extremity in children.

PMID- 14952665
TI  - A simple method of anesthesia for minor surgical procedures.

PMID- 14952666
TI  - Spinal anesthesia for spinal operations.

PMID- 14952667
TI  - Multiple mesothelial cysts of the peritoneum.

PMID- 14952668
TI  - Recurrent appendicitis in each trimester of pregnancy, with a case report in each
      trimester.

PMID- 14952669
TI  - Transection of a coronary artery during the course of mitral valvular
      commissurotomy.

PMID- 14952670
TI  - Review of 4,284 fractures.

PMID- 14952671
TI  - Congenital absence of gallbladder.

PMID- 14952672
TI  - The Bolen test for cancer.

PMID- 14952673
TI  - Successful direct aortic embolectomy.

PMID- 14952674
TI  - Acute tension pneumoperitoneum causing tension pneumomediastinum; a preliminary
      report.

PMID- 14952675
TI  - Non-traumatic diaphragmatic hernia with complete evisceration of the liver;
      repair with tantalum wire mesh.

PMID- 14952676
TI  - Anomaly of the vas deferens.

PMID- 14952677
TI  - A new aid in the management of Colles' fracture.

PMID- 14952678
TI  - Problems in wet colostomy management following radical pelvic surgery; use of a
      new giant balloon catheter.

PMID- 14952679
TI  - Treponemal immobilization test using organisms from frozen testis.

PMID- 14952680
TI  - Stethograms in cardiovascular syphilis as an aid for early diagnosis.

PMID- 14952681
TI  - Electrocardiographic changes in secondary syphilis.

PMID- 14952682
TI  - Treponemal disease control in underdeveloped countries: Experiences in mass
      therapy.

PMID- 14952683
TI  - Venereal disease conditions in the Far East.

PMID- 14952684
TI  - Second infection in treated and untreated congenital syphilis.

PMID- 14952685
TI  - Adjusting venereal disease control to the antibiotic era.

PMID- 14952686
TI  - Therapy of early syphilis with artificial fever in combination with mapharsen,
      bismuth, and penicillin.

PMID- 14952687
TI  - The effectiveness of penicillin in the prevention of congenital syphilis with a
      note on the effect of cowpox vaccination on the serologic tests of seronegative
      infants.

PMID- 14952688
TI  - Universal serologic reaction in pinta.

PMID- 14952689
TI  - A comparative study of methods of production of antisheep amboceptor.

PMID- 14952690
TI  - Nongonococcal urethritis in the Navy.

PMID- 14952691
TI  - Chancroid; a report of 1,402 cases.

PMID- 14952692
TI  - Micro-Kolmer complement fixation test for amebiasis.

PMID- 14952693
TI  - A search for liver damage in anti-amebic treatment with diodoquin, vioform and
      carbarsone.

PMID- 14952694
TI  - Some effects of cultural associates on the infectivity of a strain of Endamoeba
      histolytica for the rabbit.

PMID- 14952695
TI  - Epidemiologic appraisal of malaria in the United States during 1951.

PMID- 14952696
TI  - Densities of Anopheles, sporozoite rates in Anopheles, and incidence of malaria
      in an area of South Carolina.

PMID- 14952697
TI  - Synergistic effect of Haemobartonella muris on Plasmodium berghei in white rats.

PMID- 14952698
TI  - Relations between the endohistiocytic forms of Plasmodium gallinaceum and the
      immunological course of the infection in fowls inoculated with infected brain
      tissue.

PMID- 14952699
TI  - An antimalarial alkaloid from Hydrangea. XIII. The effects of various synthetic
      quinazolones against Plasmodium lophurae in ducks.

PMID- 14952700
TI  - The course of natural and induced infections of Plasmodium floridense Thompson
      and Huff in Sceloporus undulatus undulatus (Latreille).

PMID- 14952701
TI  - An epidemic of acute anterior poliomyelitis in Panama in 1950-1951.

PMID- 14952702
TI  - Survey of live forest animals for protective antibodies against yellow fever in
      Panama, R.P.

PMID- 14952703
TI  - Comments on the treatment of trachoma with aureomycin.

PMID- 14952704
TI  - Terramycin in the treatment of trachoma.

PMID- 14952705
TI  - The behavior of Rickettsia akari in the body louse after artificial infection.

PMID- 14952706
TI  - Effects of feeding colostrum containing Coxiella Burnetii antibodies to newborn
      calves of two categories.

PMID- 14952707
TI  - Endemic treponematosis (balash or bejel) in Saudi Arabia.

PMID- 14952708
TI  - Studies on schistosomiasis. VI. Control of the snail host of schistosomiasis in
      Japan with sodium pentachlorophenate (Santobrite).

PMID- 14952709
TI  - Three new potential intermediate hosts of human onchocerciasis in Guatemala.

PMID- 14952710
TI  - Failure of aureomycin in the treatment of schistosomiasis.

PMID- 14952711
TI  - Modified response of Anopheles albimanus to DDT residual house spraying in
      Panama.

PMID- 14952713
TI  - TRANSACTIONS of the American Society of Tropical Medicine, forty-seventh annual
      meeting, Chicago, Illinois, November 1517, 1951.

PMID- 14952712
TI  - Chronic oral toxicity and related studies on animals with the insecticide and
      pyrethrum synergist, piperonyl butoxide.

PMID- 14952714
TI  - Lung immobilizer therapy in pulmonary tuberculosis; a clinical study.

PMID- 14952715
TI  - Streptomycin and dihydrostreptomycin in the treatment of tuberculous empyema. I.
      Experimental studies of the drug concentrations attained with various vehicles.

PMID- 14952716
TI  - Streptomycin and dihydrostreptomycin in the treatment of tuberculous empyema. II.
      Studies with cellugel as vehicle.

PMID- 14952717
TI  - A method for standardization of tuberculin preparations by intracutaneous
      reactions in humans; comparison of two purified tuberculins.

PMID- 14952718
TI  - The isolation and chemistry of a protein fraction of M. tuberculosis and its
      ability to sensitize cells.

PMID- 14952719
TI  - Studies of a purified tuberculin fraction in testing BCG-vaccinated subjects; a
      preliminary study.

PMID- 14952720
TI  - Comparison of a new purified tuberculin with purified protein derivative.

PMID- 14952721
TI  - The significance of the tuberculin skin reaction in antituberculous vaccine
      assay.

PMID- 14952722
TI  - Hypopotassemia and hyponatremia in pulmonary tuberculosis during treatment with
      streptomycin and paraaminosalicylic acid.

PMID- 14952723
TI  - Adrenocortical function in pulmonary tuberculosis.

PMID- 14952724
TI  - Disturbance in carbohydrate metabolism associated with amithiozone therapy.

PMID- 14952725
TI  - A study of certain amino acids as they may relate to the problem of host
      resistance to tuberculosis.

PMID- 14952726
TI  - Problem of the so-called "Good chronic case" of tuberculosis.

PMID- 14952727
TI  - Survival of bacilli in tuberculous lesions.

PMID- 14952728
TI  - Oxidation-reduction dyes for the determination of virulence of mycobacteria in
      vitro.

PMID- 14952729
TI  - Fat embolism.

PMID- 14952730
TI  - The use of streptokinase and streptodornase in injuries of the chest.

PMID- 14952731
TI  - Bladder substitution with isolated small intestine segments; a progress report.

PMID- 14952732
TI  - Pulmonary adenomatosis and its relationship to the problem of malignant tumors of
      the lung.

PMID- 14952733
TI  - Uterine suspension indications and status.

PMID- 14952734
TI  - The repair of massive calvarial defects.

PMID- 14952735
TI  - Partial nephrectomy.

PMID- 14952736
TI  - Utilization of the aponeurosis transversus abdominis, Cooper's ligament and the
      ilio-pubic tract in the repair of inguinal and femoral hernias.

PMID- 14952737
TI  - The surgery of gallbladder disease.

PMID- 14952738
TI  - Factors in maternal mortality in South Carolina.

PMID- 14952739
TI  - Perineal prostatectomy.

PMID- 14952740
TI  - Surgery for peripheral ischemia.

PMID- 14952741
TI  - Why do patients die following anesthesia?

PMID- 14952742
TI  - Extraskeletal osteo-chondrosarcoma, review of the literature and report of a
      case.

PMID- 14952743
TI  - Megacolon, frozen section control of surgical treatment.

PMID- 14952744
TI  - Primary hyperparathyroidism with three case reports.

PMID- 14952745
TI  - Porphyria and its simulation of surgical conditions.

PMID- 14952746
TI  - Obturator hernia.

PMID- 14952747
TI  - The importance of specific antibiotic therapy in surgical infections.

PMID- 14952748
TI  - Management of the urinary bladder in the paraplegic.

PMID- 14952749
TI  - Failure of reperitonealization to prevent abdominal adhesions in the dog.

PMID- 14952750
TI  - Eosinophilic granuloma of the skull, report of six cases.

PMID- 14952751
TI  - Restoration of the skin of the male external genitalia following trauma.

PMID- 14952752
TI  - The development of sarcoma in bone subjected to irradiation, a case report.

PMID- 14952753
TI  - Intestinal antisepsis.

PMID- 14952754
TI  - Meckel's diverticulum, case report of patent omphalomesenteric duct.

PMID- 14952755
TI  - Plasma cell mastitis.

PMID- 14952756
TI  - Management of radiation injuries.

PMID- 14952757
TI  - History and physical examination in the diagnosis of acute conditions within the
      abdomen.

PMID- 14952759
TI  - [Theory of neuromuscular transfer of muscle tonus].

PMID- 14952758
TI  - The gallbladder, a pressure regulating mechanism.

PMID- 14952760
TI  - [Experiences with succinylcholinechloride, a new short acting muscle relaxant].

PMID- 14952761
TI  - [Comparison of muscle relaxants].

PMID- 14952763
TI  - [Decrease of bleeding by regulated diminution of blood pressure].

PMID- 14952762
TI  - [Side effects of curare and synthetic muscle relaxants; therapy].

PMID- 14952764
TI  - [Artificial hibernation].

PMID- 14952765
TI  - [Report from the special session "Modern Anesthesia" at the 69th Congress of
      German Surgeons in Munchen, April 17, 1952].

PMID- 14952766
TI  - [Bacillary phase of Sporotrichum schenki].

PMID- 14952767
TI  - [Scabies crustosa and a minor epidemic].

PMID- 14952768
TI  - [A case of Gougerot-Blum pigmented purpuric lichenoid dermatitis].

PMID- 14952769
TI  - [Epidermomycosis caused by a combination of 2 dermatophytes].

PMID- 14952770
TI  - [Pinta; presentation of 2 patients].

PMID- 14952771
TI  - [Lichenoid tuberculid in a patient with tuberculosis colliquativa].

PMID- 14952772
TI  - [Probable cases of Rosenbach's epysipeloid].

PMID- 14952773
TI  - [Subtropical lichen planus].

PMID- 14952774
TI  - [Atypical verrucous tuberculosis].

PMID- 14952775
TI  - [Brazilian Society of Dermatology and Syphilography; 1951 directory].

PMID- 14952776
TI  - [Boeck-Schaumann sarcoidosis].

PMID- 14952777
TI  - [Pinta; case reports].

PMID- 14952778
TI  - [Allergo-dermatological research in the printing industry].

PMID- 14952779
TI  - [Cutaneous diphtheria with localization on the external male genitals].

PMID- 14952780
TI  - [Dyschromic forms of erythema].

PMID- 14952781
TI  - [Cutaneous Mediterranean leishmaniasis; therapy].

PMID- 14952782
TI  - [Effect of terramycin on pathogenic fungi; in vitro results].

PMID- 14952783
TI  - [Spinocellular epithelioma on Puente's cheilitis glandularis].

PMID- 14952784
TI  - [New treatment of creeping eruption].

PMID- 14952785
TI  - [Familial sporotrichosis].

PMID- 14952786
TI  - [Kaposi-Irgang lupus erythematosus profundus].

PMID- 14952787
TI  - [Food allergy in dermatology].

PMID- 14952788
TI  - [Brazilian Society of Dermatology and Syphilography; 1952 directory].

PMID- 14952789
TI  - [Prof. Joaquim Motta].

PMID- 14952790
TI  - [Abdominal pregnancy].

PMID- 14952791
TI  - [Abortion: classification and treatment].

PMID- 14952792
TI  - [Adequate treatment of anemia in pregnancy].

PMID- 14952793
TI  - [Normal positive cholecystogram].

PMID- 14952794
TI  - [Strongyloides in the Rio Preto district].

PMID- 14952795
TI  - [Modern synthetic preparations in the treatment of chronic alcoholism].

PMID- 14952796
TI  - [Neurological complications of osteoma of the paranasal sinuses; a case of
      extradural pneumatocele caused by osteoma of the frontal sinus].

PMID- 14952797
TI  - [Primary melanoma of the cauda equina].

PMID- 14952798
TI  - [Heredity in degenerative psychoses].

PMID- 14952799
TI  - [Surgical treatment of coarctation of the aorta].

PMID- 14952800
TI  - [Hand burns].

PMID- 14952801
TI  - [Immunobiological relation between tuberculosis and leprosy. V. Positivation time
      of the Mitsuda reaction after simultaneous introduction of oral BCG and
      intracutaneous lepromin].

PMID- 14952802
TI  - [Kidney torsion].

PMID- 14952803
TI  - [Types of insulin with intermediate action].

PMID- 14952805
TI  - [The negative cholecystogram].

PMID- 14952804
TI  - [3rd Brazilian Conference on Gastroenterology].

PMID- 14952807
TI  - [Mediastinal tumors].

PMID- 14952806
TI  - [Extremely early ambulation in obstetrics; effect of the prevention of puerperal
      complications].

PMID- 14952808
TI  - [Function tests for veins of the leg].

PMID- 14952809
TI  - [Surgical technics in the treatment of varicose veins; presentation of the
      author's surgical instrument].

PMID- 14952810
TI  - [Inauguration of Prof. Joao Alves Meira].

PMID- 14952811
TI  - [Address upon inauguration to the Chair of Tropical and Infectious Diseases of
      the University of Sao Paulo Medical School].

PMID- 14952812
TI  - [Concept of time in the evolution of pathological processes].

PMID- 14952813
TI  - [Cholecystitis and cholesterosis; pathology and radiology].

PMID- 14952814
TI  - [Value of the examination of cerebrospinal fluid in the diagnosis of intracranial
      tumors].

PMID- 14952815
TI  - [Massive prolapse of the nucleus pulposus without radiculalgia].

PMID- 14952816
TI  - [Demyelinizing diseases of the central nervous system].

PMID- 14952817
TI  - [True value of radiography in the early diagnosis of congenital syphilis].

PMID- 14952818
TI  - [Radiology of acute abdomen in children].

PMID- 14952819
TI  - [Aureomycin therapy of amebiasis].

PMID- 14952820
TI  - [Abdominal tumors with fistulization into the sigmoid].

PMID- 14952821
TI  - [Hommage paid to the public health physicians].

PMID- 14952822
TI  - [Commemoration for Prof. Bonorino Udaondo].

PMID- 14952823
TI  - [PROFESSOR Andrew Dreyfus].

PMID- 14952824
TI  - [Rhinosinusal complications in dental processes].

PMID- 14952825
TI  - [Odontology and its clinical and therapeutic relations with the blood].

PMID- 14952826
TI  - [Early treatment of abnormalities of deciduous teeth].

PMID- 14952827
TI  - [Plea to my friends who leave the profession].

PMID- 14952829
TI  - [Measures and methods for functional treatment of malocclusion].

PMID- 14952828
TI  - [Endodontia (odontology of the interior of the tooth].

PMID- 14952830
TI  - [Endodontia (odontology of the interior of the tooth)].

PMID- 14952831
TI  - [Cardiac patient in the dental chair].

PMID- 14952832
TI  - [Earth-eaters in Peru; historical, social, and geographical data, names of edible
      earth, physiological interpretation of geophagy and pica].

PMID- 14952833
TI  - [Ophthalmological aspects of inhabitants in Andes].

PMID- 14952834
TI  - [Certain ophthalmological aspects of inhabitants of Andes].

PMID- 14952835
TI  - [Adrenal in anoxia].

PMID- 14952836
TI  - [Blood picture in high altitude].

PMID- 14952837
TI  - [Effects of cocaine on cellular excitability].

PMID- 14952838
TI  - [Studies on the physiology of inhabitants of Andes; variations of pulse and
      arterial pressure in natives of City of Huancayo].

PMID- 14952839
TI  - [Cardiologic test in anoxemia; comparative study of Levy's and Malmstrom's
      procedures and significance of electrocardiographic reactions in normal
      subjects].

PMID- 14952840
TI  - [Pseudoepiphyses].

PMID- 14952841
TI  - [The occurrence of periodic acid-leucofuchsin-positive substances in embryoes].

PMID- 14952842
TI  - [Georg Wetzel].

PMID- 14952843
TI  - [Works of Georg Wetzel].

PMID- 14952844
TI  - [International bibliography of human and vertebrate anatomy].

PMID- 14952845
TI  - The clinical use of muscle relaxants.

PMID- 14952846
TI  - Some observations on the assaying of muscle relaxant in conscious volunteers,
      with special reference to compounds 15 et 20 of the heterocyclic decamethylene
      bis quaternary ammonium series.

PMID- 14952847
TI  - The modern symptomatic therapy of tetanus.

PMID- 14952848
TI  - [Appreciation of degree of anesthesia by psychogalvanic reflex].

PMID- 14952849
TI  - [Effect of curare on circulation with remarks on the therapy of tetanus].

PMID- 14952850
TI  - [O-methyl-N-methyl bebeerine (kondrocurare); its use in anesthesia].

PMID- 14952851
TI  - [Use of R.P. 3697 (flaxedil) in anesthesia].

PMID- 14952852
TI  - Experimental and clinical investigations with celocurin (succinylcholine-iodide).

PMID- 14952853
TI  - [Intravenous R.P. 3277 (phenergan) in neurosurgery].

PMID- 14952854
TI  - [New local anesthetic: H.C. 242].

PMID- 14952855
TI  - [Pressure injector without needle for local anesthesia].

PMID- 14952856
TI  - [Local anesthesia by projection of solids under pressure].

PMID- 14952857
TI  - Invigorating surgical anesthecinesia based on pure sensory subdural or peridural
      block not affecting the anterior roots.

PMID- 14952858
TI  - [Local anesthesia according to A.V. Vichnevsky's method].

PMID- 14952859
TI  - [Role of local anesthesia according to Vichnevsky in thoracic surgery].

PMID- 14952860
TI  - [Problems of anesthesia in pulmonary surgery].

PMID- 14952861
TI  - [Ventricular fibrillation and spontaneous defibrillation during cardiac
      resuscitation].

PMID- 14952862
TI  - On the problem of anesthesia for operations of congenital malformations of the
      heart.

PMID- 14952863
TI  - [Anesthesia in surgery for hydatid cysts of the lung].

PMID- 14952864
TI  - [Technics of endobronchial anesthesia in pulmonary lobectomies and
      segmentectomies].

PMID- 14952865
TI  - [Tracheal intubation in children].

PMID- 14952866
TI  - [Anesthesia used for adenoidectomy and tonsillectomy (by disseation) in
      children].

PMID- 14952867
TI  - [The problem of cellulitis within the category of chronic rheumatic diseases;
      cellulitis and arthrosis].

PMID- 14952868
TI  - [Erythrocyanosis supramelleolaris and cellulitic infiltrations of lower limbs].

PMID- 14952869
TI  - [The cardiovascular surgery reunion of Turin].

PMID- 14952870
TI  - [Two cases of angina pectoris with emergency surgery; postoperative results up to
      23 and 10 months, respectively].

PMID- 14952871
TI  - [Vascular accident of the extremity after bismuth oil injection in the deltoid].

PMID- 14952872
TI  - [Vascular accidents from polyglobulia].

PMID- 14952873
TI  - [New synthetic anticoagulant: thrombocid].

PMID- 14952874
TI  - Thromboangiitis obliterans in two brothers.

PMID- 14952875
TI  - Conservative treatment and recovery in two cases of aortic embolism.

PMID- 14952876
TI  - Venospasm an early and late manifestation of poliomyelitis.

PMID- 14952877
TI  - Stenosing coronary arteritis; its possible role in coronary artery disease.

PMID- 14952878
TI  - Studies in aortic autografts and homografts; do homografts survive?

PMID- 14952879
TI  - The Allen test in polycythemia; the presence and interpretation of positive and
      negative reactions.

PMID- 14952880
TI  - Tobacco smoking as an etiologic factor in disease. 2. Coronary disease and
      hypertension.

PMID- 14952881
TI  - The use of hyaluronidase in the treatment of chronic skin ulcers in diffuse
      generalized scleroderma.

PMID- 14952882
TI  - Some forms of gangrene are preventable.

PMID- 14952883
TI  - [Physical fitness of ground personnel of the Air Force].

PMID- 14952884
TI  - [Biological diagnosis of so-called abacterial or viral urethritis].

PMID- 14952885
TI  - [The determination of prothrombin].

PMID- 14952886
TI  - [The application of paper microchromatography in clinical biology].

PMID- 14952887
TI  - [The determination and physiopathological variations of phenolsteroids].

PMID- 14952888
TI  - [Metabolic disorders and blood disturbances revealed by analysis in chronic
      alcoholics].

PMID- 14952889
TI  - [A contribution to the experimental study of asthma].

PMID- 14952890
TI  - [Heparin tolerance test in vitro; its technique its clinical interest].

PMID- 14952891
TI  - [A new method for measuring the activity of serum cholinesterase].

PMID- 14952892
TI  - [Determination of protein and sugar in the same sample of cerebro-spinal fluid].

PMID- 14952893
TI  - [Rapid A B O and Rh-standard blood typing of possible recipients].

PMID- 14952894
TI  - [A simple device for determination of Quick's time].

PMID- 14952895
TI  - [A note on the Addis count].

PMID- 14952896
TI  - [Considerations of a new antigen complex extracted from the living tubercle
      bacillus; its use in tubercular serology].

PMID- 14952897
TI  - [The use of plexiglass slides for flocculation reactions on slides in serology].

PMID- 14952898
TI  - [The evaluation of the serum prothrombin activity with a time technic; clinical
      value].

PMID- 14952899
TI  - [Quick's prothrombin time; security technic for a time without chronometric
      measurement].

PMID- 14952900
TI  - [Determination of plasma fibrinogen by a rapid method with thrombin].

PMID- 14952901
TI  - [The rapid and practical measure of streptomycin resistance of the tubercle
      bacillus].

PMID- 14952902
TI  - [Fractionation of proteins of pleural fluids].

PMID- 14952903
TI  - [Determination of proteins by the Biuret method according to Gornall's technic.
      III. Application to urine].

PMID- 14952904
TI  - [Determination of blood potassium].

PMID- 14952905
TI  - [The kinetics of the reaction between serum proteins and the reagent for cephalin
      cholesterol; (Hanger's reagent)].

PMID- 14952906
TI  - [The effect of ACTH and cortisone on the formation of isoglutinins].

PMID- 14952907
TI  - [The preparation of mastic suspensions of definite turbidity].

PMID- 14952908
TI  - [The reaction to Maclagan thymol test; (comparison of results given by Maclagan's
      reagent and the stable reagent according to the formula of La Huerga & Popper)].

PMID- 14952909
TI  - [Determination of urinary albumin by Gornall's technic].

PMID- 14952910
TI  - [Young cultures of the tubercle bacilli and their filterable elements].

PMID- 14952911
TI  - [Studies on the anaerobic bacteria of Adelie land (taken by the first French
      Antarctic Expedition)].

PMID- 14952912
TI  - [Schemata of abnormal lysotypes, their importance in the possible creation of new
      bacteriophagic types of S. typhi and S. paratyphi B and control of the identity
      of these Salmonella].

PMID- 14952913
TI  - [Bacteria semi-resistant to bacteriophage. I. Techniques; strains and phage used;
      lysis on gelose medium].

PMID- 14952914
TI  - [Bacteria semi-resistant to bacteriophage. II. Quantitative examination on the
      adsorption of phages by semi-resistant bacteria and the infection of same].

PMID- 14952915
TI  - [Comparison of histologic lesions induced in white rat by inoculation with
      Hansen's bacillus and various other acid-fast bacilli].

PMID- 14952916
TI  - [Conditioned reactions of hemagglutination and hemolysis in tuberculosis].

PMID- 14952917
TI  - [The determinism of sporulation of the Bacillus megatherium. II. Effect of
      deficiency of mineral constituent in synthetic medium].

PMID- 14952918
TI  - [Application of the research on bacteriophages to the study of polluted water. I.
      The survival of Enterobacteriaceae in water. II. Bacteriophages of water at large
      and small beaches].

PMID- 14952919
TI  - [Cytologic studies on a lysogenic Bacillus megatherium during the development of
      bacteriophage].

PMID- 14952920
TI  - [Two new anaerobic species: Leptotrichia haemolytica n. sp., Terminosporus
      indologenes n. sp..].

PMID- 14952921
TI  - [Anti-tuberculotic effect of the gamma-pyridine-aldehyde-thiosemicarbazone
      (G.527), isomer of G. 469].

PMID- 14952922
TI  - [Production of mutants of Shigella sonnei rapidly fermenting lactose].

PMID- 14952923
TI  - [Frequency of mutants of Shigella sonnei rapidly fermenting lactose].

PMID- 14952924
TI  - [Study on the bacterial metabolism of the cytochromes and porphyrins. Case of
      strictly anaerobic bacteria].

PMID- 14952925
TI  - [Seasonal enzootic of daces (soffies) in the Herault].

PMID- 14952926
TI  - [Rickettsioses of the Belgian Congo and Ruanda-Urundi].

PMID- 14952928
TI  - [Presence of antivirus substances in different parts of plants].

PMID- 14952927
TI  - [Effect of certain pyrimidine compounds on the growth of Sporotrichum schencki].

PMID- 14952929
TI  - [On the classification of bacteria].

PMID- 14952930
TI  - [Abortive tubercular infection of guinea pig induced by inoculation of one or
      more units of young tubercle bacilli or the pathologic products of humans with
      suspected tuberculosis or affected by this disease].

PMID- 14952931
TI  - [Research on serum antibodies of Lansing type in acute and chronic stages of
      poliomyelitis].

PMID- 14952932
TI  - [New method of production of BCG].

PMID- 14952933
TI  - [Study on the serological diagnosis of mumps. I. Reaction of complement
      fixation].

PMID- 14952934
TI  - [Hemagglutination and the virus of avian smallpox].

PMID- 14952935
TI  - [Semi-resistant bacteria to bacteriophages. III. Quantitative study on the
      production of phages by infected semi-resistant bacteria].

PMID- 14952936
TI  - [Study of the toxin R2 of the typhoid bacilli (Eberthella typhosa)].

PMID- 14952937
TI  - [The cell-microorganism conflict; induced phagocytosis].

PMID- 14952938
TI  - [Method of examination and measure of the cell-microorganism conflict.
      Sensibility and specificity].

PMID- 14952939
TI  - [Utilization of the bacteriostatic action of gentian violet for the
      differentiation of gram negative anaerobic bacteria].

PMID- 14952940
TI  - [Study of two strains of Clostridium saccharolyticum (Distaso) Bergey et al.
      1923].

PMID- 14952941
TI  - [Examination of a highly thermoresistant variety of Clostridium valerianicum].

PMID- 14952942
TI  - [Treatment of experimental tuberculosis in guinea pig by iodochloroxy quinoline].

PMID- 14952943
TI  - [Aerobacter aerogenes and Klebsiella pneumoniae].

PMID- 14952944
TI  - [The utility of combination of yeasts in the process of wine-making].

PMID- 14952945
TI  - [Hemagglutinant and infectant powers of the Newcastle virus before and after the
      death of the infected chick embryo].

PMID- 14952946
TI  - [Abdominal hernias in newborn mice inoculated with Coxsackie virus].

PMID- 14952947
TI  - [Proof of the cell role in the cell-microorganism conflict; index of cell
      activity].

PMID- 14952948
TI  - [Investigations on the decomposition of lipoprotein complexes by soaps].

PMID- 14952949
TI  - [The bacteria semiresistant to bacteriophage. IV. The effect of the concentration
      of certain ions on the behavior of semiresistant bacteria against phage. The
      significance of these bacteria].

PMID- 14952950
TI  - [The value of the characteristics of identification of Brucella].

PMID- 14952951
TI  - [The classification of Brucella. Comments concerning the identification of 2,598
      strains].

PMID- 14952952
TI  - [The purification of tetanus toxin and antitoxin].

PMID- 14952953
TI  - [The determination of sporulation of Bacillus megatherium. III. The effect of
      limiting aeration on the agitated cultures of two variants of the same strain].

PMID- 14952954
TI  - [Comparative studies of the in vitro and in vivo activity of several antibiotics.
      II. Therapeutic tests and blood concentrations].

PMID- 14952955
TI  - [Morphological alterations of the tubercle bacillus following the action of
      different medicinals. Study with the electron microscope].

PMID- 14952956
TI  - [Investigations on the nutrition of dermatophytes. I. Vitamin needs].

PMID- 14952957
TI  - [The pectinolytic activity of some anaerobic bacteria].

PMID- 14952958
TI  - [Investigations on the anaerobic intestinal flora of the normal nursing infant].

PMID- 14952959
TI  - [On the non-fixation of mineral copper by vaccinal virus].

PMID- 14952960
TI  - [Contribution to the study of the physiology of acid-alcohol resistant bacilli.
      IV. Adsorption and reduction of vital dyes by the mycobacteria].

PMID- 14952961
TI  - [Infections with Salmonella stanley in man and guinea pigs].

PMID- 14952962
TI  - [Investigations on the survival of anaerobic bacteria in sea water].

PMID- 14952963
TI  - [A study of a strain of Cl. subterminale (Hall and Whitehead) Bergey..].

PMID- 14952964
TI  - [The study of some strain of sporulated mesophi bacteria].

PMID- 14952965
TI  - [The behavior of agglutinins, precipitins and incomplete antibodies during the
      course of immunization of rabbits with human serum].

PMID- 14952966
TI  - [The allergic reactions in the course of human pasteurelloses; demonstration
      manifestations, diagnostic and therapeutic interest].

PMID- 14952967
TI  - [Clinical physiopathology of asthma].

PMID- 14952968
TI  - [Vitamin B 12 and the neuro-anemic syndromes].

PMID- 14952969
TI  - [Cinedensigraphic exploration of the intrathoracic arterial circulation, its
      application in the diagnosis of lung cancer and mediastinal tumors].

PMID- 14952970
TI  - [Absence of acetone in the blood and fresh excreted urine during ketosis].

PMID- 14952971
TI  - [Embryonic hemorrhages caused by deficiency in linoleic acid].

PMID- 14952972
TI  - [ACTH and cortisone in pediatrics].

PMID- 14952973
TI  - [Electroencephalogram in tuberculous meningitis].

PMID- 14952974
TI  - [A case of subacute sclerotic leuko-encephalitis].

PMID- 14952975
TI  - [Electrological and clinical correlations in the study of epilepsy; unity and
      plurality of traditional epilepsy].

PMID- 14952976
TI  - [Anatomo-pathological examination of the brain of a patient with dementia praecox
      dying during electronarcosis 23 months after a lobotomy].

PMID- 14952977
TI  - [Cushing syndrome with confusion and psychosis symptomatic of a
      craniopharyngioma].

PMID- 14952978
TI  - [Attempted suicide by unusual means: hammering nails into skull].

PMID- 14952979
TI  - [Effect of lobotomy on behavior of a psychotic epileptic].

PMID- 14952980
TI  - [Shock therapy of a catatonic syndrome; attempt at systematic treatment].

PMID- 14952981
TI  - [Results of occupational therapy with a young Moslem schizophrenic for several
      years].

PMID- 14952982
TI  - [Experiment with an occupational rehabilitation service in a small Tunisian
      agricultural community].

PMID- 14952983
TI  - [Embryopathy caused by rubeola with epilepsy].

PMID- 14952985
TI  - [Address of the retiring president].

PMID- 14952984
TI  - [Neuropsychiatric manifestations of ascariasis].

PMID- 14952986
TI  - [President's address].

PMID- 14952987
TI  - [Problems of old age].

PMID- 14952988
TI  - [Effect of electroshock on manic-depressive psychoses and involutional
      melancholia; statistical study].

PMID- 14952989
TI  - [Recklinghausen's disease and a depersonalization syndrome].

PMID- 14952990
TI  - [Treatment of alcoholism by creating a conditioned reflex after inhibition
      without chemotherapy].

PMID- 14952992
TI  - [Alcoholism therapy and the concept of abstinence].

PMID- 14952991
TI  - [Observations deduced from 10 years' practice in the treatment of alcoholism].

PMID- 14952993
TI  - [Criteria for the treatment of alcoholism].

PMID- 14952994
TI  - [Contact between the psychiatrist in public services and his patients].

PMID- 14952995
TI  - [Familial obsessional neurosis of periodic evolution].

PMID- 14952996
TI  - [Rare mental automatism syndrome in a 15 year old girl].

PMID- 14952997
TI  - [Some economic aspects of the utility of nutritional investigations].

PMID- 14952998
TI  - [Methods of inquiry with families and some cases of application studied by the
      National Institute of Statistics and Economic studies].

PMID- 14952999
TI  - [Investigations on the social nutritional habits in a population of French manual
      workers of a Parisian mixture; researches of social ethnography in the Parisian
      aggregation].

PMID- 14953000
TI  - [Nutritional investigations; their significance for rural economy].

PMID- 14953001
TI  - [Public and private action of the nutritional investigation].

PMID- 14953002
TI  - [Methods of determination of vitamins PP and B2; microbiological technics].

PMID- 14953003
TI  - [Dental caries in its relations with feeding and nutrition].

PMID- 14953004
TI  - [Not Available].

PMID- 14953005
TI  - [The big atonic colon in certain forms of obstipation in children and its therapy
      with sympatholytics].

PMID- 14953006
TI  - [ADE milk; additional proposals to vitaminize bottle milk in Switzerland].

PMID- 14953007
TI  - [Directives for surgery of newborn].

PMID- 14953008
TI  - [Cuprichlorid crystallization in a case of endocarditis].

PMID- 14953009
TI  - [Purpura fulminans].

PMID- 14953010
TI  - [Fat tolerance of newborn. II. Investigations on the bile acid and lipase content
      in the duodenal juice in fat intolerance].

PMID- 14953011
TI  - [Disorders of fat resorption in newborn].

PMID- 14953012
TI  - [Modern aspects of lipid metabolism].

PMID- 14953013
TI  - [Xerophthalmia in pancreas fibrosis].

PMID- 14953014
TI  - [Bacon in nutrition].

PMID- 14953015
TI  - [Therapy of cystic fibrosis of pancreas associated with bronchiectasia with
      antibiotics; reference to the results of sensitivity tests].

PMID- 14953016
TI  - [Conservation of human milk with special reference to lipase].

PMID- 14953017
TI  - [Fat metabolism in infants].

PMID- 14953018
TI  - [Neurological pathology of newborn].

PMID- 14953019
TI  - [Acute anatomic problems in neuropathology of first years of life].

PMID- 14953020
TI  - [Therapy of severe toxic diphtheria with cocarboxylase].

PMID- 14953021
TI  - [Acute hemolytic anemia associated with thrombocytopenic purpura caused by
      autoantibodies].

PMID- 14953022
TI  - [Icterus gravis neonatorum caused by A-O incompatibility].

PMID- 14953023
TI  - [Constitutional infantile panmyelopathy (Fanconi's syndrome) effects of cortisone
      and ACTH].

PMID- 14953024
TI  - [Thrombopathias in the first years of life].

PMID- 14953025
TI  - [Symptoms and hematology of the Stevens-Johnson syndrome; (pluriorificial
      ectodermosis)].

PMID- 14953026
TI  - [Early transfusion of fresh blood in therapy of toxicosis of newborn].

PMID- 14953027
TI  - [Diagnosis of polycoric lipoidosis].

PMID- 14953028
TI  - [The biology of Trichomonas. I. Polymorphism and multiple division in culture].

PMID- 14953029
TI  - [The natural rodent hosts of Schistosoma rodhaini Brumpt].

PMID- 14953030
TI  - [Diagnosis of pulmonary bilharziasis].

PMID- 14953031
TI  - [Description of a new species of the genus Metathalazia (Nematoda-Spiruroidea)].

PMID- 14953032
TI  - [Capillaria of the lapwing].

PMID- 14953033
TI  - [A new culicidine in France: Uranotaenia unguiculata Edw; ecology].

PMID- 14953034
TI  - [Terramycin and experimental toxoplasmosis in the rabbit].

PMID- 14953035
TI  - [The genus Giardia Kunstler, 1882 (Mastigophora: Octomitidae). I. Synoptic list
      of known and four new species].

PMID- 14953036
TI  - [Tunisian habitats of Anopheles multicolor and antimalarial prophylaxis].

PMID- 14953037
TI  - [The social evolution of pharmacy. III. Payments for prescriptions under social
      security].

PMID- 14953038
TI  - [Colchicoside].

PMID- 14953039
TI  - [Calculation of some elimination constants (hemikresis and protorrhea) in the
      case of incomplete curves and their clinical applications].

PMID- 14953040
TI  - [Action of periodic acid on riboflavin].

PMID- 14953041
TI  - [Xanthydrol reagent for desoxy sugars].

PMID- 14953042
TI  - [Critical study of the determination of the total alkaloids in an extract of nux
      vomica (Codex 1937 and 1949].

PMID- 14953043
TI  - [Essence of Ormenis Multicaulis (Braun-Blanquet and Maire) grown in Morocco].

PMID- 14953044
TI  - [Criminal poising of a group of men by Datura seeds, followed by one death].

PMID- 14953045
TI  - [A historical point on some classical reactions used in the determination of
      blood pigments].

PMID- 14953046
TI  - [Principal researches on antibacterial chemotherapy grouped according to some
      fundamental concepts and hypotheses].

PMID- 14953047
TI  - [The social evolution of pharmacy. IV. Payments for prescriptions under social
      security].

PMID- 14953048
TI  - [Experimental research on the phenomena of shock observed during intravenous
      injections. II. Comparison between citric shock and various other types of shock,
      especially anaphylactic shock].

PMID- 14953049
TI  - [Triiodothyronine and its presence in thyroid proteins].

PMID- 14953050
TI  - [Measurement of the spreading power of hyaluronidase by means of radioactive
      isotopes; application to sodium para-aminosalicylate].

PMID- 14953051
TI  - [Comparative biological activity of leaves of wild Digitalis purpurea and of
      various species of Digitalis cultivated on a horticultural scale].

PMID- 14953052
TI  - [Some amino alcohol derivatives of diphenyl-methane and of diphenylamine].

PMID- 14953053
TI  - [Mechanical analysis applied to the study of fine mineral powders used in
      pharmacy].

PMID- 14953054
TI  - [The colorimetric determination of tocopherol].

PMID- 14953055
TI  - [Testing the sterility of antibiotics].

PMID- 14953056
TI  - [Action of digitalis on the heart and on the circulation].

PMID- 14953057
TI  - [Vitamin B12].

PMID- 14953058
TI  - [The retirement of pharmacists].

PMID- 14953059
TI  - [Colchicoside. II. Partial synthesis and structure].

PMID- 14953060
TI  - [Inhibition of the effects of various local anesthetics on the rabbit cornea by
      means of polyhydroxy compounds].

PMID- 14953061
TI  - [Research on the mechanism of inhibition of local anesthesia: the antagonistic
      action of urea].

PMID- 14953062
TI  - [Research on some synthetic antibiotics. III. Polynitrobenzenes and dinitro
      halobenzenes].

PMID- 14953063
TI  - [Research on some synthetic antibiotics. IV. Relation between bacteriostatic
      action and mobility of nitro groups in dinitrophenols and in polynitrobenzenes].

PMID- 14953064
TI  - [Research on some synthetic antibiotics. V. Relation between bacteriostatic
      action and mobility of nitro groups and halogen groups in dinitro-halobenzenes].

PMID- 14953065
TI  - [Semi-micro determination of carbon monoxide in the blood].

PMID- 14953066
TI  - [New spasmolytics derived from 1-phenyl-isoquinoline].

PMID- 14953067
TI  - [Action of caffeine and of some preparations of coffee on isolated guinea pig
      intestine].

PMID- 14953068
TI  - [Pharmacodynamic action of food preservatives].

PMID- 14953069
TI  - [Accumulation of drugs in the body].

PMID- 14953070
TI  - [A cause of error in the gravimetric determination of calcium from calcium
      sulfate].

PMID- 14953071
TI  - [Identification and determination of the free and combined forms of caffeine in
      extracts of kola obtained by the usual method and by nebulization].

PMID- 14953072
TI  - [The saponosides of two sarsaparilla plants (Smilax ornata Lem. and Smilax
      japicanga Griseb.) used against leprosy].

PMID- 14953073
TI  - [Study of some derivatives of oxazolidinedione].

PMID- 14953074
TI  - [Colchicoside and colchicine. III. Some peculiarities in their powers of optical
      rotation].

PMID- 14953075
TI  - [Modifications in the formation of penicillin by Penicillium chrysogenum Thom. by
      successive division and thinning out of cultures].

PMID- 14953076
TI  - [The presence of ursolic acid in the leaves of Vinca minor L., Nerium oleander L.
      and Salvia officinalis L].

PMID- 14953077
TI  - [The bulb of scilla].

PMID- 14953078
TI  - [Pharmacodynamic action of food preservatives].

PMID- 14953079
TI  - [Opening lecture on microbiology given the 3rd of March 1952 at the Faculty of
      Pharmacy of Paris].

PMID- 14953080
TI  - [Raticidal effects of tomorin, an oxycoumarin derivative].

PMID- 14953081
TI  - [Prophylactic control of sleeping sickness in the Maniema region 1938-50].

PMID- 14953082
TI  - [A potassium emetic resistant strain of Trypanosoma gambiense in the Kibombo
      region].

PMID- 14953083
TI  - [An endoglobular parasite in the dendrohyrax].

PMID- 14953084
TI  - [Streptomycin resistance of Koch's bacillus in lower Congo].

PMID- 14953085
TI  - [Bovine globidiosis in Ruanda-Urundi].

PMID- 14953086
TI  - [The banana plantations, hatching places for Glossina palpalis v. martinii, on
      the Ruzizi plains].

PMID- 14953087
TI  - [The development of Plasmodium berghei in the atroparvus variant of Anopheles
      maculipennis].

PMID- 14953088
TI  - [Longevity and vitality of dermatophytes cultivated in a medium with soil base].

PMID- 14953089
TI  - [Biological technique for isolating dermatophytes from soil].

PMID- 14953090
TI  - [The Salmonella of Belgian Congo].

PMID- 14953091
TI  - [A case of congenital malaria in Belgium].

PMID- 14953092
TI  - [Physiopathology of general venous circulation in obliterating arterial diseases
      of the lower extremities].

PMID- 14953093
TI  - [Pulmonary decortication in chronic empyema].

PMID- 14953094
TI  - [Repair of aortic defect by osteogenic heterotopic grafting of the ureter and of
      the kidney pelvis].

PMID- 14953095
TI  - [Inguinal hernia; considerations and review of 166 cases operated by Bassini's
      method].

PMID- 14953096
TI  - [Nephro-omentopexy in the revascularization of the kidney; experimental
      contribution].

PMID- 14953097
TI  - [Prothrombin activity of preserved human blood in relation to the anticoagulant
      used].

PMID- 14953098
TI  - [Blood protein precipitation curves in salt solutions. I. Separation of
      fibrinogen].

PMID- 14953099
TI  - [Thorn test with ACTH and variations in eosinophil count following surgery].

PMID- 14953100
TI  - [Surgical treatment of congenital atresia of the anus with opening into the
      vagina].

PMID- 14953101
TI  - [Effect of ultrasonics on ossification; experimental studies].

PMID- 14953102
TI  - [Thorn test in surgery and intra- and postoperative eosinophil variations].

PMID- 14953103
TI  - [Curve of protein precipitation in saline solution; globulin].

PMID- 14953104
TI  - [Case of solitary renal cyst].

PMID- 14953105
TI  - [Case of psoriasis follicularis].

PMID- 14953106
TI  - [Initial results on the effects of phenoxyethyl-dimethyl-dodecyl ammonium bromide
      combined with benzyl-(pyridyl)-dimethylethylenediamine in various forms of
      pyogenic eczematization].

PMID- 14953107
TI  - [Minimal and latent forms of lichen follicularis keratosus atrophicans the pseudo
      area].

PMID- 14953108
TI  - [Case of psoriasis and cancer].

PMID- 14953109
TI  - [Helminthiasis of epidemiological interest in Somaliland (ancylostomiasis and
      schistosomiasis) and on the adoption of means to combat them].

PMID- 14953110
TI  - [Duties and organization of the national quarantine services].

PMID- 14953111
TI  - [Transitory pulmonary opacities; Loeffler syndrome and so-called Fanconi-Hegglin
      pseudosyphilitic bronchopneumonia].

PMID- 14953112
TI  - [Contribution to the study of acute benign liver diseases].

PMID- 14953113
TI  - [Our experience with Filatov tissue therapy].

PMID- 14953114
TI  - [An instance of acute gastroenteritis of dietary origin aboard ship; nutritional
      toxinfections on ships].

PMID- 14953115
TI  - [Heterophoria, hypermetropia and moderate anisometropia in regard to the fitness
      of military radar specialists].

PMID- 14953116
TI  - [Treatment of erythema solare].

PMID- 14953117
TI  - [9th International Congress on Athletic Medicine].

PMID- 14953118
TI  - [G. B. Morgagni and its observations on obstetrics and gynecology].

PMID- 14953119
TI  - [Studies on hemostasis in functional metrorrhagia in puberty].

PMID- 14953120
TI  - [Spinal anesthesia with hyperbaric nupercaine in gynecological surgery].

PMID- 14953121
TI  - [Glycogen content in the vaginal cells and hormonal genital function].

PMID- 14953122
TI  - [Endocrinologic study of vaginal cytology with a rapid method of staining].

PMID- 14953123
TI  - [Obstetric trauma causing detachment of the epiphysis of the extremity proximal
      to the tibia; clinical and radiological study].

PMID- 14953124
TI  - [Cranial calcifications of difficult interpretation].

PMID- 14953125
TI  - [Stratigraphy in localization of mediastinohilar tuberculosis in children].

PMID- 14953126
TI  - [Splenography by intraparenchymal infection into human and bovine isolated
      spleen].

PMID- 14953128
TI  - Body weight at different ages and heights.

PMID- 14953127
TI  - Further data on genetics of microcythaemia or thalassaemia minor and Cooley's
      disease or thalassaemia major.

PMID- 14953129
TI  - Blood groups in Jews from the Yemen.

PMID- 14953130
TI  - A statistical study of human twinning.

PMID- 14953131
TI  - Blood agglutinogens of the Mexicans.

PMID- 14953132
TI  - Simple tests for bimodality and bitangentiality.

PMID- 14953133
TI  - Birth weight and length of gestation of twins, together with maternal age, parity
      and survival rate.

PMID- 14953134
TI  - Data on the genetics of birth weight.

PMID- 14953135
TI  - The evolution of modern tendon surgery.

PMID- 14953136
TI  - On the prevention and treatment of shock and anaemia in civilian trauma.

PMID- 14953137
TI  - Ulcerative colitis and Crohn's disease.

PMID- 14953138
TI  - Ureteric calculus.

PMID- 14953139
TI  - Hyperplasia and metaplasia in synovial membrane.

PMID- 14953140
TI  - The transplantation of homologous tissue and its surgical applications.

PMID- 14953141
TI  - IN MEMORIAM, Sir Hugh Cairns, K.B.E., D.M., F.R.C.S.

PMID- 14953142
TI  - Return of function after complete transection of the spinal cord of the rat, cat
      and dog.

PMID- 14953143
TI  - Observations of spinal nerve root transplantation in the male guinea baboon.

PMID- 14953144
TI  - A comparative study of subtotal gastrectomy with and without infra-diaphragmatic
      vagotomy in the surgical therapy of duodenal ulcer.

PMID- 14953145
TI  - Cysts of the adrenal glands.

PMID- 14953146
TI  - The use of viably preserved tissue for homologous arterial grafts.

PMID- 14953147
TI  - Splenic studies. I. Susceptibility to infection after splenectomy performed in
      infancy.

PMID- 14953148
TI  - Acute appendicitis in children.

PMID- 14953149
TI  - Brain hemorrhage after carotid-jugular anastomosis; implications of changes in
      walls of blood vessels.

PMID- 14953150
TI  - The use of "dramamine" in the prevention of postoperative nausea and vomiting.

PMID- 14953151
TI  - Enzymatic debridement of necrotic surfaces.

PMID- 14953152
TI  - Repair of abdominal wall defects with fortisan fabric; experimental study.

PMID- 14953153
TI  - Some unusual manifestations of regional enteritis and their surgical management.

PMID- 14953154
TI  - Intrathoracic duplications of the alimentary tract communicating with the small
      intestine.

PMID- 14953155
TI  - Duplication of the terminal ileum; report of a case operated upon successfully on
      the fifth day of life.

PMID- 14953157
TI  - Pulmonary hydatid (echinococcic) cyst; report of native case.

PMID- 14953156
TI  - Congenital cystic disease of the lung in the newborn; report of a successful left
      lower lobectomy in a seven-day-old infant.

PMID- 14953158
TI  - Transplantation of the tibia and fibula to replace the femur following resection.

PMID- 14953159
TI  - Islet cell carcinoma of the pancreas; report of a survival of eight years.

PMID- 14953160
TI  - The phrenic rebound phenomenon--a new physical sign.

PMID- 14953161
TI  - Volvulus of the cecum; with report of two cases.

PMID- 14953162
TI  - Successful, progressive, massive resection of small and large bowel for
      mesenteric carcinomatous metastases.

PMID- 14953164
TI  - "The professor of surgery".

PMID- 14953163
TI  - Substitute bladder after pelvic evisceration for treatment of radiation necrosis.

PMID- 14953165
TI  - A case for the study of the humanities in the making of a doctor.

PMID- 14953166
TI  - Some physiologic aspects of surgical trauma.

PMID- 14953167
TI  - The use of radioactive iodinated human serum albumin in evaluating the peripheral
      circulation.

PMID- 14953168
TI  - Surgical treatment of progressive exophthalmos.

PMID- 14953169
TI  - Trapezius paralysis following minor surgical procedures in the posterior cervical
      triangle; results following cranial nerve suture.

PMID- 14953170
TI  - The therapeutic use of the radioactive isotopes in intracranial tumors.

PMID- 14953171
TI  - The tripartite deltoid and its surgical significance in exposure of the
      scapulohumeral joint.

PMID- 14953172
TI  - A study of the vascularization of experimental bone grafts by means of
      radioactive phosphorus and the transparent chamber.

PMID- 14953173
TI  - Preservation of the facial nerve in operations for benign conditions of the
      parotid area.

PMID- 14953174
TI  - The role of venous endothelium in the inception of thrombosis.

PMID- 14953175
TI  - An experimental study of the effects of preservation on the fate of aortic and
      vena-caval homografts in the growing pig.

PMID- 14953176
TI  - Direct surgery of arteriosclerosis.

PMID- 14953177
TI  - Successful experimental maintenance of life by homologous lungs and mechanical
      heart.

PMID- 14953178
TI  - The reaction of the coronary blood pressure to graded stages of shock
      (hemorrhage).

PMID- 14953179
TI  - The surgical significance of pulmonary hypertension.

PMID- 14953180
TI  - Control of heart action by repetitive electrical stimuli.

PMID- 14953181
TI  - Intrathoracic tracheal tumors: development of surgical technics for their
      removal.

PMID- 14953182
TI  - The influence of external body radiation on mortality from thermal burns.

PMID- 14953183
TI  - A comparison of plasma expanders with blood and plasma as a supplement to
      electrolyte solutions in the treatment of rats undergoing third degree burns of
      fifty per cent of the body surface.

PMID- 14953184
TI  - Length of stride, stride frequency, "flight" period and maximum distance between
      the feet during running with different speeds.

PMID- 14953185
TI  - How do stride length and stride frequency influence the energy-output during
      running?

PMID- 14953186
TI  - [Stereoscopic vision in hypoxemia].

PMID- 14953187
TI  - [Studies on work with hammers or axes].

PMID- 14953188
TI  - [The effect of work on the metabolism of ketone bodies in diabetics].

PMID- 14953189
TI  - [The effect of stimulants and food intake on pulse rate during work].

PMID- 14953190
TI  - [Tool type, performance and energy-output in screwdriving].

PMID- 14953191
TI  - [A light breathing valve that can be worn at the mouth].

PMID- 14953192
TI  - [Energy transformation in carrying weight up stairs].

PMID- 14953193
TI  - [The measurement of energy consumption in occupational work with an improved
      respiratory-gasmeter].

PMID- 14953194
TI  - [Skin reaction to biogenic amines and their therapy].

PMID- 14953195
TI  - [Triphenyltetrazoliumchlorid in investigation of vehicles].

PMID- 14953196
TI  - [Foreign body granulomata and sarcoidosis].

PMID- 14953197
TI  - [Fluorescency and fluorochromation of normal skin].

PMID- 14953198
TI  - [Fluorescence and fluorochromation of abnormal skin. I. Basal- and spinal cell
      carcinomata].

PMID- 14953199
TI  - [Morphology of normal and abnormal skin].

PMID- 14953200
TI  - [IV. Penicillin effects on thyroid function of rat].

PMID- 14953201
TI  - [Investigations on the effects of penicillin. V. Effects of penicillin
      application of longer duration on the vitamin C content of the adrenal cortex of
      the rat].

PMID- 14953203
TI  - [Experimental studies on the effects of BAL, BAL intravenous and methionin on
      letal thallium intoxication in animals].

PMID- 14953204
TI  - [Histological picture of an immature follicular naevus].

PMID- 14953205
TI  - [Diffuse generalized scleroderma].

PMID- 14953206
TI  - [Morphological changes of the guinea pig skin caused by ointments].

PMID- 14953207
TI  - [Investigations on the effects of penicillin. IV. Effects of longer lasting
      penicillin application on the sympathicoadrenal system of the rat].

PMID- 14953202
TI  - [Histology of toxoplasmosis of skin; with reference to the whole literature on
      toxoplasmosis].

PMID- 14953208
TI  - [Investigations on penicillin effects. VII. Effects of penicillin on isolated
      frog heart].

PMID- 14953209
TI  - [Experimental and clinical investigations on the combined penicillin-rutin
      therapy of skin diseases].

PMID- 14953210
TI  - [Histochemical investigations on oxidation, reduction and lipoid metabolism in
      the psoriatic lesion].

PMID- 14953211
TI  - [Investigations of spinal fluid cells by the phase contrast microscope. II.
      Disintegrating round cells in the cerebrospinal fluid in syphilis. Hypothesis of
      pathogenesis of round cells and causes for their disintegration].

PMID- 14953212
TI  - [A hitherto rare dermatomyces in Germany: Microsporon gypseum].

PMID- 14953213
TI  - [Associated abnormalities in skin hemangioma].

PMID- 14953214
TI  - [Symptoms and histology of granulomatosis disciformis chronica et progressiva
      (Miescher); atypical sarcoid].

PMID- 14953215
TI  - [A spot method to determine traces of arsenic in biological material].

PMID- 14953216
TI  - [Methanol and Widmark method of determination].

PMID- 14953217
TI  - [The biological importance of the high zinc content of snake venoms. Zinc as
      inhibitor of snake venoms].

PMID- 14953218
TI  - [Lipotropic action of vitamine E and cystine, methionine, inosit and invert sugar
      on the rat poisoned with carbon tetrachloride].

PMID- 14953219
TI  - [Effects of the substitution of aniline by the methyl group on the formation of
      hemoglobin (methemoglobin) and the general toxicity of the compound].

PMID- 14953220
TI  - [Separated determination of 11-oxy- and 11-desoxycorticoids methods and a few
      results].

PMID- 14953221
TI  - [Investigation of bromides].

PMID- 14953222
TI  - [The effects of magnesium in contrast to the effects of curarine and nicotine].

PMID- 14953223
TI  - [Organ specifity of histamine receptors].

PMID- 14953224
TI  - [Reversal of arterenol effects after application of sympatholytics on the
      intestines].

PMID- 14953225
TI  - [Modified nephelometric method for determination of morphine abuses].

PMID- 14953226
TI  - [A new method for quick colorimetrid determination of pyramidone in the serum].

PMID- 14953227
TI  - [An electrically regulated gas valve].

PMID- 14953228
TI  - Equidistance concept and structure-activity relationship of curarizing drugs.

PMID- 14953229
TI  - [Figures of concentration as a way to determine of produce final concentrations
      in experiments in vitro].

PMID- 14953230
TI  - [Cardiac effect of a few sympathomimetics causing peripheral vasodilation].

PMID- 14953231
TI  - [Technique of flame photometry in the clinic].

PMID- 14953232
TI  - [A method to determine the conduction speed of the excitation in the frog heart
      in order to determine pharmacological substances].

PMID- 14953233
TI  - [Effect of homologous compounds of cystamine in blood coagulation].

PMID- 14953234
TI  - [Correlations between thyroid gland and muscle atrophy].

PMID- 14953235
TI  - [Effects of ultrasonics].

PMID- 14953236
TI  - [Histochemical investigations on the effects of monoiodoacetic acid, phlorhizin
      and hyaluronidase on alkaline phosphatase on the cornea].

PMID- 14953237
TI  - [Elimination of the sense of smelling in long lasting experiments with artificial
      fats].

PMID- 14953238
TI  - [Paradox effect of vitamin E on diuresis, dependent on dosage].

PMID- 14953239
TI  - [Effects of ACTH, 11-dehydro-and 11-desoxicorticosterone on experimental
      animals].

PMID- 14953240
TI  - [Comparison of effects of anterior pituitary extracts, ACTH and cortisone on egg
      white hyperergia of rats].

PMID- 14953241
TI  - [Relation of blood alcohol and alcohol in breath].

PMID- 14953242
TI  - [Reversible inactivation of the thyreotrope hormone].

PMID- 14953243
TI  - [Similarity of results of clearance tests].

PMID- 14953244
TI  - [Antagonistic effects of monoiodoacetic acid and desoxycorticosterone acetate on
      the dye phagocytosis of rats].

PMID- 14953245
TI  - [Effects of methylthiouracil and dijodthyrosine].

PMID- 14953246
TI  - [Hypotension caused by d-tubocurarine; antagonistic effect of prostigmine].

PMID- 14953247
TI  - [Attempts to demonstrate a specific erythropoetic hormone. II].

PMID- 14953248
TI  - [Quantitative investigations of the lipids of the human serum].

PMID- 14953249
TI  - [Pharmacodynamic passage determination on dogs in connection with severing of the
      superior mesenteric plexus].

PMID- 14953250
TI  - [Excretion of 17-ketosteroids in the rat].

PMID- 14953251
TI  - [Quantitative determination of sedative effects in animal experiments].

PMID- 14953252
TI  - [Investigations on the vitamin T complex Goetsch by means of tissue culture].

PMID- 14953253
TI  - [Renal tubuli in intravital microscope].

PMID- 14953254
TI  - [Thiosemicarbazones and tissue respiration; studies on the destruction of
      conteben].

PMID- 14953255
TI  - [Thiosemicarbazones and hyaluronidase].

PMID- 14953256
TI  - [Effects of bees venom on skeletal muscle of the frog].

PMID- 14953257
TI  - [Problems of leucocyte metabolism. III. Effects of nitrogen mustard and nitrogen
      mustard in combination with urethan on the metabolism of cells of myeloid
      leukemia].

PMID- 14953258
TI  - [Inhibition of cholinesterase by prostigmine].

PMID- 14953259
TI  - [Effects of laevulsoe on the methanol poisoning of the rat].

PMID- 14953260
TI  - [Mercury effects and osmotic diuresis in dog].

PMID- 14953261
TI  - [Enteral resorption of g-strophanthin K-strophanthol gamma and digitoxin in the
      cat].

PMID- 14953262
TI  - [Paradox atropine effects on isolated organs; statistical registration].

PMID- 14953263
TI  - [Evaluation of cough remedies].

PMID- 14953264
TI  - [Myotropic effects of adrenal androgens].

PMID- 14953265
TI  - Renal vascular changes produced by the mercurial diuretic salyrgan.

PMID- 14953266
TI  - [Effects of adrenochrome on isolated organs].

PMID- 14953267
TI  - [Histamine as a mediator substance in the adrenochrome effects on the bleeding
      time].

PMID- 14953268
TI  - [Tension of the diaphragm and width of the bronchi].

PMID- 14953269
TI  - [Epinephrine and arterenol content of the adrenal hormone in relaxation of the
      carotid body and in electric irritation of the splanchnic nerve].

PMID- 14953270
TI  - [Effects of alpha amanitin, the poison of amanita phalloides].

PMID- 14953271
TI  - [Androgens with protracted effects].

PMID- 14953272
TI  - [Functional changes in the central nervous system by electrically and chemically
      induced convulsions].

PMID- 14953273
TI  - [Effects of ephedrine and neosynephrine on the caroid sinus].

PMID- 14953274
TI  - [Effects of a few alpha, omega bis-quarternary ammonium compounds on the skeletal
      musculature].

PMID- 14953275
TI  - [Inhibition of parasympathetic receptors by fagarin].

PMID- 14953276
TI  - [Adrenalin content of the adrenal glands after cooling and histamine shock].

PMID- 14953277
TI  - [A sympathomimetic effect of histamine].

PMID- 14953278
TI  - [Determination of posterior pituitary gland extracts on the isolated guinea pig
      uterus by the means of registration mean contraction values in the final
      position].

PMID- 14953279
TI  - [Solution of metallic iron in the gastrointestinal tract].

PMID- 14953280
TI  - [Additional results in blocking bee and snake venoms by zinc salts].

PMID- 14953281
TI  - [Effects of methionine-choline (hepsan) on chronic liver poisoning with
      pentothal].

PMID- 14953282
TI  - [Metabolic problems of obesity; nitrogen metabolism].

PMID- 14953283
TI  - [Demonstration of chemical changes in proteins by dye absorption and
      electrophoresis].

PMID- 14953284
TI  - [Investigation on liberation and distribution of ACTH in parabiotic animals].

PMID- 14953285
TI  - The epidemiology of paralysis in poliomyelitis.

PMID- 14953286
TI  - A comparative study on muscular involvement in experimental poliomyelitis induced
      by various strains of virus, and the effect of hyaluronidase on the intramuscular
      inoculation.

PMID- 14953287
TI  - An experimental study on the effect of immunization with T.A.B. and pertussis
      vaccine and alum-precipitated diphtheria toxoid on the centripetal and
      centrifugal neural spread of poliomyelitis virus.

PMID- 14953288
TI  - Human pneumonitis viruses and their classification.

PMID- 14953289
TI  - Studies on the sedimentation of influenza virus.

PMID- 14953290
TI  - Evidence for the propagation of the virus of serum hepatitis in the chick embryo.

PMID- 14953291
TI  - [Experimental dates in favor of viral etiology of human leukemia].

PMID- 14953292
TI  - The agglutination of chicken erythrocytes with special reference to avian
      histone.

PMID- 14953293
TI  - [Physiology of human erythrocytes in the Hirst test for influenza virus].

PMID- 14953294
TI  - [Dysplastic-idiotic children of mothers with ovarial insufficiency].

PMID- 14953295
TI  - [Pathological changes of the ovaries caused by age and disease].

PMID- 14953296
TI  - [Effects of female sex hormones on the leucocytary phagocytosis in vitro;
      metabolic action of female sex hormones].

PMID- 14953297
TI  - [Fructose metabolism in pregnancy].

PMID- 14953298
TI  - [Incidence of iso-agglutination during pregnancy; its role in pathogenesis of
      fetal erythroblastosis].

PMID- 14953299
TI  - [Histological glycogen demonstration in endometrium in evaluation of ovarian
      cycle].

PMID- 14953300
TI  - [Experimental implantation of the ovary into the spleen].

PMID- 14953301
TI  - [Correlations of the histological tumor type of the collum carcinoma to the long
      range surgical healing and therapy of this disease].

PMID- 14953302
TI  - [An example how to evaluate biological periods; duration of pregnancy in relation
      to body height].

PMID- 14953303
TI  - [Ligation of the ovarial mesenterium causing anatomic and functional genital
      disorders].

PMID- 14953304
TI  - [Vital-cytological evaluation of the maturity degree of the carcinoma of the
      portio].

PMID- 14953305
TI  - [Role of the collagenous fiber system in widening of the uterine cervix during
      delivery].

PMID- 14953306
TI  - [Deliveries from pelvic presentation. Improvement of results by use of
      spasmolytics. Report on 666 cases in the year 1937-1948].

PMID- 14953307
TI  - [Periarteritis nodosa of the female genitalia].

PMID- 14953308
TI  - [X-ray picture of the uterus without tubes].

PMID- 14953309
TI  - [Ovarial changes in hormone therapy of breast carcinoma].

PMID- 14953310
TI  - [Genesis and therapy of chorioepithelioma malignum].

PMID- 14953311
TI  - [Investigations of blood slides of retroplacental hematoma; permeability of the
      placenta for fetal blood cells].

PMID- 14953312
TI  - [The importance of the solubility of silicic acid in the pathogenesis of the
      pneumoconioses].

PMID- 14953313
TI  - [Suggestions on the bacteriological examination of ice cream].

PMID- 14953314
TI  - [Transmission of ectromelia from mouse to mouse by serial inoculations of a
      sterile solution; an experimental study on the etiology of inoculation
      hepatitis].

PMID- 14953315
TI  - [A survey of the nutritional status of West Berliners].

PMID- 14953316
TI  - [Comparative studies of new rapid serodiagnostic tests for syphilis].

PMID- 14953317
TI  - [Saccharophilic oral microorganisms; Leuconostoc, Candida Oospora, Micrococcus
      luteus].

PMID- 14953318
TI  - [The bacteriostatic and bactericidal effect of derivatives of the phenazine
      group].

PMID- 14953319
TI  - [Fatal rabies without history of injury or contact with animals proven of
      suspected to be rabid].

PMID- 14953320
TI  - [Effects of ultrasonics on typhoid bacilli].

PMID- 14953321
TI  - [Immunological processes in the fertilized chicken egg; effects of
      chloromycetin].

PMID- 14953322
TI  - [Typhoid fever in Bavaria; reference to age and sex].

PMID- 14953323
TI  - [Effects of a practically harmless milk preservative Mx on milk and its bacterial
      content].

PMID- 14953324
TI  - [Control of venereal diseases in Greater Berlin in the years 1945-1949].

PMID- 14953325
TI  - [To Jussuf Ibrahim on his 75th birthday].

PMID- 14953326
TI  - [Pathogenesis and therapy of toxicosis in infancy].

PMID- 14953327
TI  - [Studies of the electrocardiogram, cardiophonogram and blood chemistry in
      pylorospasm; the significance of serum electrolytes for ECG changes in
      pylorospasm].

PMID- 14953328
TI  - [Excretion of amino acids in prematures].

PMID- 14953329
TI  - [On pathogenesis of rubella embryopathy].

PMID- 14953330
TI  - [Not Available].

PMID- 14953331
TI  - [Intraspinal course and endings of the sensory roots into the gracilis and
      cuneatus nuclei].

PMID- 14953332
TI  - [Personality, work legacy and psychosis of Charles Meryons].

PMID- 14953333
TI  - [Pathological altruism].

PMID- 14953334
TI  - [Deterioration of the human speech].

PMID- 14953335
TI  - [The drawing test of Wartegg in psychiatric diagnosis (with special consideration
      of response to the test)].

PMID- 14953336
TI  - [Organic brain diseases and reversal of drives].

PMID- 14953337
TI  - [Periodic unconsciousness and paroxysmal comata in a case of primary oliguira
      after brain injury; on the problem of genuine disorders of consciousness in
      diseases of the pituitary gland and the diencephalon].

PMID- 14953338
TI  - [Experiences with prefrontal leucotomy in psychoses].

PMID- 14953339
TI  - [Non-penetrating brain injury seen from the viewpoint of anatomical physics].

PMID- 14953340
TI  - [Electroencephalographic changes in infantile poliomyelitis; clinical and
      electroencephalographic studies of the epidemic in 1950].

PMID- 14953341
TI  - [Manic-depressive and related psychoses caused by brain injury].

PMID- 14953342
TI  - [Clinical experiences on the reliability of the modified hippuric acid test and a
      new supporting liver therapy in schizophrenia].

PMID- 14953343
TI  - [Psychopathology, pathophysiology, morphology of atypical atrophic diseases in
      the brain; comments on the theory of compulsion].

PMID- 14953344
TI  - [Polioencephalitis hemorrhagica Wernicke in disorders of gastrointestinal
      resorption].

PMID- 14953345
TI  - [Manifestation of an occipital vertebra with basal impression resembling multiple
      sclerosis].

PMID- 14953346
TI  - [Pathogenesis of spinal cavitations and neoplasms on the basis of dysraphia].

PMID- 14953347
TI  - [A modified operation of neoplasms of the tuberal part of the pituitary gland].

PMID- 14953348
TI  - [Arteriographically demonstrated occlusion of the vertebral artery].

PMID- 14953349
TI  - [Problem of optic agnosia].

PMID- 14953350
TI  - [Fright reflex and reaction caused by organic brain damage].

PMID- 14953351
TI  - [Tribute to Professor George Dubreuil].

PMID- 14953352
TI  - [Investigations on the distribution of minerals in the basic substance of bone].

PMID- 14953354
TI  - [The thecal gland in the guinea pig ovary].

PMID- 14953353
TI  - [The teratogenic capacity of certain chemical substances and in particular that
      of apomorphine].

PMID- 14953355
TI  - [Destruction and reconstruction of the nuclear membrane during mitosis].

PMID- 14953357
TI  - [Nerve fiber and cartilage: an example of intertissular incompatibility].

PMID- 14953356
TI  - [Considerations on the distribution of respiratory capillaries in the alveolar
      wall of the vertebrate lung in its relationships with the intrinsic and extrinsic
      mechanical factors of respiration].

PMID- 14953358
TI  - [Differentiation and behaviour of osteoclasts in birds].

PMID- 14953359
TI  - [Observations on the determinism of aberrant decidual reactions of the female
      genital tract].

PMID- 14953360
TI  - [Concerning synapses and their relationships with the neuroglia].

PMID- 14953361
TI  - [The estrus cycle persists in the ovary of the pregnant guinea pig].

PMID- 14953362
TI  - [A new contribution concerning the neuro interstitial relations in the genital
      glands of primate].

PMID- 14953363
TI  - [Endocrine activity of the placenta in the rat].

PMID- 14953364
TI  - [Benign tumors of the stomach; a histo-pathologic study].

PMID- 14953365
TI  - [Comparative skeletal modifications in birds during egg laying].

PMID- 14953366
TI  - [Observations on the histological analogies of two biglandular endocrine systems;
      the pituitary-neurohypophyseal complex and the cortico-paraganglionic suprarenal
      complex].

PMID- 14953367
TI  - [On several anomalies of pregnancy obtained through hormonal mechanism].

PMID- 14953368
TI  - [A histochemical contribution to the study of ossification and bone elongation].

PMID- 14953369
TI  - [Effects of centrifugation on the secondary oocyte and the undivided fertilized
      ovum of the rat].

PMID- 14953370
TI  - [The phosphatase activity of the islet cells of the pancreas of the rat and its
      variation during experimental procedures].

PMID- 14953371
TI  - [Tumor of the interstitial gland of the testes in the rabbit].

PMID- 14953372
TI  - [The morphology of the mandibular meniscus].

PMID- 14953373
TI  - [Mitosis and differentiation; new thoughts on the biochemical regulation of
      growth in the vertebrates].

PMID- 14953374
TI  - [The kidney arrangement in Cepola rubescens L].

PMID- 14953375
TI  - [The effect of implants of pig pituitary basophils on the thyroid].

PMID- 14953376
TI  - [The value of the thymus].

PMID- 14953377
TI  - [The role of elastic tissue in the insertion of certain muscle fibers].

PMID- 14953378
TI  - [Blood platelets, thrombocytes and nuclear remains of erythrocytes].

PMID- 14953379
TI  - [The age of the fetus as a factor in the degeneration of extremities induced by
      certain pituitary preparations; in the rat].

PMID- 14953380
TI  - [Notes on the experimental analysis of the endocrinology of pregnancy].

PMID- 14953381
TI  - [Information on regeneration and cicatrization of nerves].

PMID- 14953382
TI  - [An account of the osteogenic properties of skeletal tissue extracts].

PMID- 14953383
TI  - [Structure of the connective membrane (wall proper) of the testicular and
      epididymal canalicules in man and several mammals].

PMID- 14953384
TI  - [What is the importance of the ganglionar apparatus of the thyroid gland?].

PMID- 14953385
TI  - [The lung structure; the respiratory and vascular lobules].

PMID- 14953386
TI  - [Labelled thyroxine; endocrine receptors and interrelations].

PMID- 14953387
TI  - [The composition of the Meckelian primordial branchial skeleton; its phylogenetic
      variations; the invo-evolutive processes observed in man].

PMID- 14953388
TI  - [The innervation of the human cornea].

PMID- 14953389
TI  - [Histophysiology of the progestative and gestative bodies].

PMID- 14953390
TI  - [The influence of certain hormone, vitamin and pharmacodynamic factors on the
      suprarenal medulla].

PMID- 14953391
TI  - [The nucleolar vacuolization induced by thiourea in the hepatic cells of the
      white mouse].

PMID- 14953392
TI  - [An endocrine type tumor resembling a thecal metaplasia of the mesenchymatous
      stroma of the human ovary].

PMID- 14953393
TI  - [Histologic images of neurosecretion in an intrasuprarenal sympathetic ganglion
      of the horse].

PMID- 14953394
TI  - [A half century of histology (1900-1951); some recollections].

PMID- 14953395
TI  - [Ultrasonics and the nerves of the ear].

PMID- 14953396
TI  - [Alkaline phosphatases in the pituitary of the cat and their presence in the
      Golgi apparatus in the cells of the anterior pituitary].

PMID- 14953397
TI  - [Transformations in the achromatic apparatus and chromosomes in normal and
      blocked mitoses of the dividing egg].

PMID- 14953398
TI  - [The production of double monsters in Rana fusca by centrifugation of undivided
      eggs].

PMID- 14953399
TI  - [The action of hormone mixtures on sex differentiation of the male chick embryo].

PMID- 14953400
TI  - [The influence of the suprarenal on the corticotropic secretion of the
      pituitary].

PMID- 14953401
TI  - [Applications of the reactions of 9-phenyl'2,3,7-tri-hydroxy-6-fluorone
      (reactions of Turchini, Castel and Khau-Van-Kien) to the study of nuclei of plant
      cells].

PMID- 14953402
TI  - [Histochemical criteria for the functional activity of the adrenal cortex in
      mammals].

PMID- 14953403
TI  - [Manifestations of the instability of nerve endings in encephalon of a teleost].

PMID- 14953404
TI  - [Multiple visceral malformations in the newborn].

PMID- 14953405
TI  - [Histological phenomenon of the regression of the Mullerian ducts in the male
      chick embryo].

PMID- 14953406
TI  - [Dangerous side effects of cancer therapy].

PMID- 14953407
TI  - [Statistical study of endemic tuberculosis in Belgium].

PMID- 14953408
TI  - [Committee for the study of measures to be taken to prevent abuse of streptomycin
      and other antibiotics].

PMID- 14953409
TI  - Exchange reactions and phosphoglyceric acid in photosynthesis.

PMID- 14953410
TI  - Photochemical carbon dioxide fixation by cell-free leaf macerates.

PMID- 14953411
TI  - An electrophoretic analysis of tobacco mosaic virus biosynthesis.

PMID- 14953412
TI  - The role of B12 in methionine synthesis in E. coli.

PMID- 14953413
TI  - The action of oxygen on glucose in the presence of potassium hydroxide.

PMID- 14953414
TI  - Intracellular distribution of assimilated C14 in briefly exposed aquatic plants.

PMID- 14953415
TI  - The competitive effects of metallic ions on citrate oxidation. II.

PMID- 14953416
TI  - Conversion of a phosphorylated ketohexose (D-fructose 6-phosphate) to a
      phosphorylated aldopentose derivative (D-arabonic acid 5-phosphate).

PMID- 14953417
TI  - Polyethenoid fatty acid metabolism. V. Prooxidant-antioxidant effect.

PMID- 14953418
TI  - Estimation of proteolytic enzymes by means of their fibrinolytic activity.

PMID- 14953419
TI  - Potentiometric titration of unidentified serum constituents.

PMID- 14953420
TI  - The inactivation of dry penicillin by deuteron bombardment.

PMID- 14953421
TI  - The basic proteins of Aspergillus fumigatus with tumor-inhibiting properties.

PMID- 14953422
TI  - Studies on mold lipase; comparative study of lipases obtained from molds grown on
      Sesamum indicum.

PMID- 14953423
TI  - Vitamin B12 and carbon dioxide production by chick embryo.

PMID- 14953424
TI  - Studies on the cyclophorase system. XXI. Condensation reactions involving
      glycine.

PMID- 14953425
TI  - Separation and determination of antimycins.

PMID- 14953426
TI  - The effect of folic acid on glycine toxicity in the chick.

PMID- 14953427
TI  - The effect of terramycin on the growth of rabbits.

PMID- 14953428
TI  - The biosynthesis of ergosterol from isotopic acetate.

PMID- 14953429
TI  - Biochemical studies on Penicillium chrysogenum Q-176. II. Further investigations
      on phosphatase activity.

PMID- 14953430
TI  - Paper chromatography of steroid compounds.

PMID- 14953431
TI  - Anionic stimulation of the Hill reaction in isolated chloroplasts.

PMID- 14953432
TI  - Apyrase, pyrophosphatase and metaphosphatase of Penicillium chrysogenum.

PMID- 14953433
TI  - The transition from the primary to the secondary peroxidase-peroxide complex.

PMID- 14953434
TI  - Electronic structure of the peroxidase-peroxide complexes.

PMID- 14953435
TI  - The structure of "active acetyl" and a theory of fatty acid catabolism.

PMID- 14953436
TI  - Studies on the biosynthesis of cholesterol. II. Isolation of 3 beta, 5 alpha
      dihydroxy-6-ketocholestane from cholesterol.

PMID- 14953437
TI  - Heat of reaction between trypsin and soybean trypsin inhibitor.

PMID- 14953438
TI  - A rapid method for the determination of sodium in biological fluids.

PMID- 14953439
TI  - Effect of penicillin on the tolerance of turkeys to fat.

PMID- 14953440
TI  - Incorporation of glycine-1-C14 and adenine-8-C13 in the purines of a purine
      requiring yeast.

PMID- 14953441
TI  - The preparation and metabolism of tyrosine disulfonate.

PMID- 14953442
TI  - A model for the elementary process in muscle action.

PMID- 14953443
TI  - The mechanism of catalase action. I. Steady-state analysis.

PMID- 14953444
TI  - The mechanism of catalase action. II. Electric analog computer studies.

PMID- 14953445
TI  - A continuous membrane diffusion column.

PMID- 14953446
TI  - Combinations of modified serum gamma-globulin with other proteins.

PMID- 14953447
TI  - Choline oxidase and endogenous respiration in liver homogenates from x-irradiated
      rats.

PMID- 14953448
TI  - The mechanism of the cyanide inhibition of fermentation.

PMID- 14953449
TI  - Isolation and characterization of a trypsin inhibitor from lima beans.

PMID- 14953450
TI  - An ACTH-inactivating factor in mammalian blood.

PMID- 14953451
TI  - Effect of aliphatic alcohols on bovine alkaline phosphatases.

PMID- 14953452
TI  - The thermodynamics of free energy transfer in certain models of muscle action.

PMID- 14953453
TI  - The in vitro metabolism of 3 alpha, 17 beta-androstanediol by liver and kidney.

PMID- 14953454
TI  - The determination of hemovanadin and its oxidation potential.

PMID- 14953455
TI  - A new method for determining hydrodynamic volumes.

PMID- 14953456
TI  - The fortification of bread with lysine. II. The nutritional value of fortified
      bread.

PMID- 14953457
TI  - Effect of salt on the hydrolysis of acetylcholine by cholinesterases.

PMID- 14953458
TI  - The action of phosphoglucomutase preparations on ribose 1-phosphate.

PMID- 14953459
TI  - Albumins from the three albuminous layers of the hen's egg.

PMID- 14953460
TI  - Composition and fractionation of ovomucoid.

PMID- 14953461
TI  - The nephrotic syndrome in children treated with ACTH and cortisone.

PMID- 14953462
TI  - Cortisone treatment of nephrosis.

PMID- 14953463
TI  - Retrolental fibroplasia.

PMID- 14953464
TI  - A comparative study of the circulating eosinophil level in babies. Part I.
      Premature infants.

PMID- 14953465
TI  - Galactosaemia.

PMID- 14953466
TI  - Appendix. Paper chromatographic investigations on the urine of patients R.T. and
      R.R.

PMID- 14953467
TI  - Polyostotic fibrous dysplasia.

PMID- 14953469
TI  - Chronic pancreatitis in childhood.

PMID- 14953468
TI  - Cystinosis.

PMID- 14953470
TI  - Torsion of the ovary in childhood.

PMID- 14953471
TI  - The successful removal of an anterior mediastinal teratoma from an infant.

PMID- 14953472
TI  - Haematogenous osteitis of infancy.

PMID- 14953473
TI  - Radiographs of the hand as an index of skeletal maturity in infants.

PMID- 14953474
TI  - Evidence of post-natal environmental influence in the aetiology of infantile
      pyloric stenosis.

PMID- 14953475
TI  - Two cases of Hand-Schuller-Christian disease in infancy.

PMID- 14953476
TI  - Paroxysmal tachycardia in infancy.

PMID- 14953477
TI  - The restoration of normal breathing in asthmatic children.

PMID- 14953478
TI  - [Epidemic of Brandenburg Salmonella infections in nursery of maternity hospital].

PMID- 14953479
TI  - [Diffuse eosinophilic granuloma in a 5-year-old child; relation to allied
      reticuloses].

PMID- 14953480
TI  - [Acute infectious pulmonary atelectasis simulating bronchial pneumonia in infant;
      symptomatology and treatment].

PMID- 14953481
TI  - [A rare case of Gougerot-Houwers-Sjogren syndrome or xerodermosteosis with
      precocious development of the genital organs and body, in a child].

PMID- 14953482
TI  - [Two cases of precocious puberty in mongoloids].

PMID- 14953483
TI  - [Principal hematological data in normal newborn infants].

PMID- 14953484
TI  - [Origin of the brachyesophagus].

PMID- 14953485
TI  - [Malformation called "congenital fistula of the lips"].

PMID- 14953486
TI  - [Two cases of destruction of the nasal partition by infection, associated with
      osteomyelitis of the extremities].

PMID- 14953487
TI  - [Anatomo-radio-clinical study of giant emphysema of the upper lobe in a one-month
      old child].

PMID- 14953488
TI  - [Multiple urinary lithiasis in child].

PMID- 14953489
TI  - [Double renal ectopia with median symphysis (caked kidney) in a 17-month-old
      girl].

PMID- 14953490
TI  - [A fatal case of periodic vomiting with acetonemia; anatomical, and pathological
      examination of the brain].

PMID- 14953491
TI  - [The use of barbiturates in infantile neuropsychiatry].

PMID- 14953492
TI  - [First tests of ACTH therapy of Syndenham's chorea].

PMID- 14953493
TI  - [Successful results of intra-articular injections of thrombin solutions, after
      irrigation of the joint in the treatment of hemophilic joint diseases].

PMID- 14953494
TI  - [Pierre Mauriac syndrome; neuro-endocrine origin; glyco-lipidic surcharge of the
      liver].

PMID- 14953495
TI  - [A case of fetal peritonitis].

PMID- 14953496
TI  - [Costal osteo-chondroma with thoracic development; first manifestation of an
      exostotic disease; surgery; recovery].

PMID- 14953497
TI  - [Congenital cyst of the posterior mediastinum in a 5-year-old child; surgery;
      recovery].

PMID- 14953498
TI  - [Forty-three tubercular children vaccinated with B.C.G.S.P in 1942-1943].

PMID- 14953499
TI  - [Seventeen cases of anti-Rhesus iso-immunization of mothers].

PMID- 14953500
TI  - [Hyper immunization of mothers against agglutinogen A with recurrent fetal
      deaths].

PMID- 14953501
TI  - [The social problem of blood incompatibility in marriage].

PMID- 14953502
TI  - [Pulmonary edema in infants; 48 cases].

PMID- 14953503
TI  - [Treatment of congenital syphilis in infants].

PMID- 14953504
TI  - [Treatment of pulmonary pyosclerosis in infants by elective resections].

PMID- 14953505
TI  - [Eduard Glanzmann].

PMID- 14953506
TI  - [Bourneville's sclerosis tuberosa in infant and small child].

PMID- 14953507
TI  - [Scurvy and collagenosis].

PMID- 14953508
TI  - [Problems of mortality of newborn infants].

PMID- 14953509
TI  - [A case of pre-pubertal anemia; the role of estrogens].

PMID- 14953510
TI  - [Cooley's disease; major thalassemia in two brothers].

PMID- 14953511
TI  - [Antibiotic therapy of dyspepsias].

PMID- 14953512
TI  - [Superior cerebellar peduncle syndrome after frontoparietal fracture in 10-year
      old child].

PMID- 14953513
TI  - [Relations between acrodynia and polyradiculoneuritis; Guillain-Barre syndrome].

PMID- 14953515
TI  - [Intra-pulmonary angioma].

PMID- 14953514
TI  - [A case of eosinophilic granuloma of the bone in a 10-month-old child].

PMID- 14953516
TI  - [Two cases of acute primary asystolia in 4-year-old children; cortisone and ACTH
      therapy; recovery].

PMID- 14953517
TI  - [Von Jaksch-Luzet's pseudo-leukemic infantile anemia and rickets].

PMID- 14953518
TI  - [Acrodynia and mercury in the urine].

PMID- 14953519
TI  - [The role of mercury in acrodynia; nine cases].

PMID- 14953520
TI  - Dual vasomotor actions of sparteine.

PMID- 14953521
TI  - Some pharmacologic comparisons of 1-ethoxy, 3-isopropoxypropane-2-ol and 3,-(2
      methylphenoxy) propane-1,2-diol (myanesin).

PMID- 14953522
TI  - [Pharmacology of alpha omega-bis quaternary ammonium compounds; IV. Effects of
      bis-choline ester of sebacic acid on respiration and blood pressure].

PMID- 14953523
TI  - [Circulatory effects of parathion].

PMID- 14953524
TI  - [Electroencephalographic investigation of narcotics of hypnotics].

PMID- 14953525
TI  - The influence of unilateral lumbar sympathectomy on the udder of the sheep.

PMID- 14953526
TI  - The effect of diphenhydramine HCL (benadryl HCL) on skeletal muscle.

PMID- 14953527
TI  - Sparteine on mammalian circulation.

PMID- 14953528
TI  - [First experimental contribution to the pharmacology of iridomyrmecin].

PMID- 14953529
TI  - Studies on the crystallization of pyrexin, the pyrogenic factor of inflammatory
      exudates.

PMID- 14953530
TI  - [Choleretic action of N-acetylsalicylamid].

PMID- 14953531
TI  - [Investigations on the pharmacology of khellin].

PMID- 14953532
TI  - Subcortical action of metrazol, tris-b-chlorethyl amine and cyanide. Role of
      carbon dioxide.

PMID- 14953533
TI  - [Antagonistic effects of metabolic inhibitor and activator on the potassium loss
      of erythrocytes].

PMID- 14953534
TI  - [Leucopenic action of podophyllin; activity of different fractions].

PMID- 14953535
TI  - [Vago-insulinic system and phagocytosis of the leukocytes].

PMID- 14953536
TI  - [Effects of hydergin on cholinesterase of the human blood].

PMID- 14953537
TI  - The effect of pentamethylentetrazol (metrazol) and 2-methylamine-6-hydroxy-6
      methylheptane (aranthol) on the respiratory and cardiovascular disturbances in
      pentothal sodium intoxication.

PMID- 14953538
TI  - [Desoxycorticosterone-percorten, peripheral vascular permeability factor].

PMID- 14953539
TI  - [Importance of the oxygen and carbondioxide content of the perfusion fluid in the
      effect of g-strophanthin on the isolated mammalian heart].

PMID- 14953540
TI  - Effect of cardioactive glycosides on a sympathetic ganglion.

PMID- 14953541
TI  - [Pharmacology of new synthetic parasympatholytics].

PMID- 14953542
TI  - [Action of two pyrites on the electrocardiogram of the dog].

PMID- 14953543
TI  - [Pharmacology of alkyl-polyethyleneoxide derivatives. II. Effects on the phrenic
      nerve & diaphragm preparation of the rat].

PMID- 14953544
TI  - [Determination of analgetic effects in animal experiment III. Quantitative
      determination of local analgetics on the dog head].

PMID- 14953545
TI  - Erythrophleum and digitalis principles comparative effects on heart contractile
      force.

PMID- 14953546
TI  - Does meso-inositol inhibit the colchicine effect in the roots of Allium Cepa?

PMID- 14953547
TI  - [Determination of central analgetic effects].

PMID- 14953548
TI  - The role of acetaldehyde in the TETD-ethyl-alcohol syndrome.

PMID- 14953549
TI  - The prolongation of the anticonvulsant activity of 5,5 diphenylhydantoine in rats
      by partial hepatectomy.

PMID- 14953550
TI  - [Effect of painful stimuli on the intestinal glucose resorption].

PMID- 14953551
TI  - [Procaine amide and toxic ventricular estrasystolies].

PMID- 14953552
TI  - The effect of various solutions upon barbiturate anesthesia.

PMID- 14953553
TI  - [Right ventricular hypertrophy in congenital heart disease; physiological
      classification of electrocardiographic modifications].

PMID- 14953554
TI  - [Visibility of the left auricle on front view radiographies in mitral stenosis].

PMID- 14953555
TI  - [Electromagnetic ballistocardiogram in normal subjects and in coronary disease].

PMID- 14953556
TI  - [Clinical and electrocardiographic study of 9 cases of acute cor pulmonale].

PMID- 14953557
TI  - [Semeiology of tricuspid lesions].

PMID- 14953558
TI  - [Contribution to the study of reactions of microglia of the central nervous
      system in acute rheumatism].

PMID- 14953559
TI  - [Anatomical and clinical comparison; pseudocoronary electric images].

PMID- 14953560
TI  - [Study on the law governing the division of electrocardiographic types from the
      thoracic wall; idea of plan O].

PMID- 14953561
TI  - [Ventricular origin of Bouveret's disease].

PMID- 14953562
TI  - [Unusual variation of Morgagni-Adams-Stokes syndrome during dental infection].

PMID- 14953563
TI  - [Occupational allergic dermatoses; importance of history, investigation of
      location and tests].

PMID- 14953564
TI  - [Therapy of experimental parathion intoxication].

PMID- 14953565
TI  - [The lungs of quarrymen and limestone cutters].

PMID- 14953566
TI  - [Effects of age and silicosis on the vital capacity and maximal ventilation;
      study and discussion of a statistic].

PMID- 14953567
TI  - [Commission of reclassification of Nancy; critical study of 9 years of
      functioning].

PMID- 14953568
TI  - [Official bulletin society of medicine and health; meeting of 19 November 1951].

PMID- 14953569
TI  - [Relative value of certain laboratory methods in prevention of lead poisoning].

PMID- 14953570
TI  - [Blood nitrogen levels in workers exposed to lead].

PMID- 14953571
TI  - [Aplastic anemia caused by carbon monoxide poisoning].

PMID- 14953572
TI  - [Nervous disorders caused by carbon monoxide poisoning].

PMID- 14953573
TI  - [Value of vestibular chronaxy in carbon monoxide intoxication].

PMID- 14953574
TI  - [Practical considerations in the diagnosis of chronic carbon monoxide poisoning
      in coal distillation; criteria to interrupt or resume work].

PMID- 14953575
TI  - [Carbon monoxide intoxication in metallurgy].

PMID- 14953576
TI  - [The risk of carbon monoxide intoxication in blast furnace workers].

PMID- 14953577
TI  - [Mass intoxication with carbon monoxide in mines].

PMID- 14953578
TI  - [Chronic carbon monoxide poisoning].

PMID- 14953579
TI  - [Statistical studies on chronic carbon monoxide intoxication in drivers of
      vehicles fed by city gas and other gases].

PMID- 14953580
TI  - [Second Congress of National Technical Security and hygiene].

PMID- 14953581
TI  - [Histological and physiopathological research on pulmonary silicosis].

PMID- 14953582
TI  - [Pneumoconioses from silica of fossil origin].

PMID- 14953583
TI  - [Two cases of accidental poisoning by trichloroethylene].

PMID- 14953584
TI  - [Toxicology of fluids used in cold wave permanents].

PMID- 14953585
TI  - [Regulations concerning soaps].

PMID- 14953586
TI  - [Asthmas from para-phenylenediamine].

PMID- 14953587
TI  - [Employment of subnormal adolescents in industry].

PMID- 14953588
TI  - [Blood platelets in the diagnosis and prognosis of benzol poisoning].

PMID- 14953589
TI  - [Myeloid leukemia in a workman exposed to vapors of pitch].

PMID- 14953590
TI  - [Dermatitis caused by hexamethylenediamine].

PMID- 14953591
TI  - [Labyrinthitis following exposure to accidental electric arc flash (10,000
      amperes)].

PMID- 14953592
TI  - [Statistics on work accidents and occupational diseases from 1948 to 1950].

PMID- 14953593
TI  - [Model for annual reports of physicians in industrial medicine].

PMID- 14953594
TI  - [Social security and salaried physicians].

PMID- 14953595
TI  - [Use of antiparasitic substances with diethylthiophosphate and paranitrophenyl
      bases; precautions in handling; anti-intoxication measures].

PMID- 14953596
TI  - [Prevention of poisoning by diethylthiophosphate and paranitrophenyl].

PMID- 14953597
TI  - [Chlorinated derivatives of acyclic hydrocarbons; provisions concerning labeling
      of containers].

PMID- 14953598
TI  - Intermittent hypertension due to phaeochromocytoma.

PMID- 14953599
TI  - The neurohypophysis and the regulation of water excretion.

PMID- 14953600
TI  - Thrombotic and toxic forms of hydrocephalus.

PMID- 14953601
TI  - The pre-operative assessment of patients before prostatectomy.

PMID- 14953602
TI  - Carcinoma of the breast.

PMID- 14953603
TI  - Meconium ileus.

PMID- 14953604
TI  - Hydrops foetalis.

PMID- 14953605
TI  - Diagnostic problems. No. 6, Erythema nodosum.

PMID- 14953606
TI  - [The principal vitamins and their use in ophthalmology].

PMID- 14953607
TI  - [Ocular symptoms of myasthenia].

PMID- 14953608
TI  - [Etiology of retinal periphlebitis].

PMID- 14953609
TI  - [Influence of corneoscleral sutures on the astigmatism present after cataract
      extraction].

PMID- 14953610
TI  - [Central tapetoretinal degeneration].

PMID- 14953611
TI  - [New viewpoints on the origin of squint].

PMID- 14953612
TI  - Necrologie: Jacques Bollack (1883-1951).

PMID- 14953613
TI  - [Local provocation of a primary dental focus as a diagnostic method in cases of
      uveitis of focal etiology].

PMID- 14953614
TI  - [Body section roentgenography in a case of olfactory meningioma with residual
      exophthalmos after surgery].

PMID- 14953615
TI  - [Five cases of retinal angiomatosis; therapeutic aspects].

PMID- 14953616
TI  - [Effect of narcosis, of curare, and of ganglioplegics on intraocular tension].

PMID- 14953617
TI  - [Some differences between the results of ophthalmometry and the Donders method].

PMID- 14953618
TI  - [Primary cancer of the cornea].

PMID- 14953619
TI  - Spontaneous rupture of the lens in hydrocephalic epilepsy; report of case.

PMID- 14953620
TI  - Incontinence of urine and the neurogenic bladder in childhood with illustrative
      case.

PMID- 14953621
TI  - Coexisting coccidioidomycosis and tuberculosis in children; report of three
      cases.

PMID- 14953622
TI  - Coarctation of the aorta and patent ductus arteriosus; report of case.

PMID- 14953623
TI  - Diphtheria in early life.

PMID- 14953624
TI  - [Alcoholic narcosis in fishes].

PMID- 14953625
TI  - [Vitamin control of nitrogen metabolism; role of biotin].

PMID- 14953626
TI  - [Uric acid and diabetes mellitus].

PMID- 14953627
TI  - [The photoelectric effect observed during unilateral illumination of the epicotyl
      of Vicia faba].

PMID- 14953628
TI  - [Segmental bronchitis due to tuberculous lymphadenitis].

PMID- 14953629
TI  - [Histological study on polymorphism in bronchial carcinoma].

PMID- 14953630
TI  - [Middle lobe syndrome; entity characteristic of late pathology of hilar
      lymphadenitis].

PMID- 14953631
TI  - [Histological study on experimental pulmonary atelectasis with special reference
      to reversibility of lesion].

PMID- 14953632
TI  - [Glycemia following experimental pulmonary resection].

PMID- 14953633
TI  - [Vitamin K and endocrine glands].

PMID- 14953634
TI  - [Effect of ascorbic acid therapy on urinary 17-ketosteroids].

PMID- 14953635
TI  - [Effect of orthobiotic serum therapy on urinary 17-ketosteroids in normal and
      pathologic conditions].

PMID- 14953636
TI  - [First results with a new contrasts medium (ethyl dliodostereate in glucosated
      water) in experimental hepato-splenography and lymphography preliminary
      communication].

PMID- 14953637
TI  - [Pituitary-adrenal relationship; histological changes of the adrenal glands in
      albino rat and in guinea pig following implantation of eosinophil and basophil
      stained hog anterior pituitary and following injection of ACTH].

PMID- 14953638
TI  - [Pituitary and testicular histological changes in adult guinea pig treated with
      various doses of testosterone propionate].

PMID- 14953639
TI  - [Adrenal changes in adult male guinea pig treated with various doses of
      testosterone propionate].

PMID- 14953640
TI  - [Proteinemia and protein fractions in thromboembolic diseases, thrombogenic
      diathesis, and hemorrhagic diseases].

PMID- 14953641
TI  - [Medical treatment of parapneumothoracic empyema; preliminary note].

PMID- 14953642
TI  - [Essential chronic leukoneutropenia; case reports and nosologic considerations].

PMID- 14953643
TI  - [Urinary 17-ketosteroids in pulmonary tuberculosis in relation to collapse,
      streptomycin, and TB1/698 therapy].

PMID- 14953644
TI  - [Electrophoretic study of the blood in hyperthyroidism with special reference to
      roentgenotherapy].

PMID- 14953645
TI  - [Chemical determination of adrenocortical hormones].

PMID- 14953646
TI  - [Theoretical principles and clinical application of oxyhemometry; studies with
      the oxyhemometer of a new type].

PMID- 14953647
TI  - [Action of 4-methyl-2-thiouracii and of thiourea on glycogen reserve in the
      liver].

PMID- 14953648
TI  - [Systemic histopathologic study of regional lymph nodes in malignant epithelial
      neoplasms].

PMID- 14953649
TI  - [Pathogenesis of anemic infarcts of the liver; case reports].

PMID- 14953650
TI  - [Primitive metastasing malignant tumors of the digestive system, biliary tract,
      and pancreas].

PMID- 14953651
TI  - [Critical considerations on papillary cystadenoma lymphomatosum; observations on
      three cases].

PMID- 14953653
TI  - [Adrenal cysts; anatomical and pathological considerations].

PMID- 14953652
TI  - [Intramural diffusion of cancer in the colon, sigmoid, and rectum].

PMID- 14953654
TI  - [Histomorphological changes of the endocrine glands in hypertensive experimental
      nephrosclerosis; study in young dogs].

PMID- 14953655
TI  - [Histopathologic study on late lesions produced by thorotrast].

PMID- 14953656
TI  - [Presence of epithelial inclusions in a lymph node of the liver hilus].

PMID- 14953657
TI  - [Regional senile arteritis; case of bilateral arteritis of the perforating
      branches of the mammary artery].

PMID- 14953658
TI  - [Aldo Fabris].

PMID- 14953659
TI  - [Anatomo-histo-pathological profile of primary malignant mesenchymal tumors of
      the pancreas; cases of fusocellular sarcoma and lymphosarcoma].

PMID- 14953660
TI  - [Case of eosinophilic granuloma of the cecum].

PMID- 14953661
TI  - [Megalobulbus].

PMID- 14953662
TI  - [Anatomosurgical study of pseudocysts of the pancreas].

PMID- 14953663
TI  - [Importance of the study of the cytological picture of bronchial secretion for
      the early diagnosis of pulmonary cancer].

PMID- 14953664
TI  - [Comparative anatomy and function of the labyrinth].

PMID- 14953665
TI  - [Blood vascularization in cancer of the larynx].

PMID- 14953666
TI  - [Value of antroscopy for the diagnosis of maxillary sinus infections].

PMID- 14953667
TI  - [Nasal cytology in normal and pathological conditions].

PMID- 14953668
TI  - [Effect of streptomycin on pupillary modifications from sound stimulation].

PMID- 14953669
TI  - [Aureomycin in otorhinolaryngology].

PMID- 14953670
TI  - [Determination of urinary nicotinic acid and trigonelline in nicotinic acid
      tolerance test].

PMID- 14953671
TI  - [Studies on urinary elimination of nicotinic acid, nicotinuric acid, and
      trigonelline in nicotinic acid and its amides tolerance tests].

PMID- 14953672
TI  - [Glycemia, fructosemia, and glucosemia following oral tolerance test of fructose
      and saccharose in a normal child].

PMID- 14953673
TI  - [Congenital disease of the bladder neck in children].

PMID- 14953674
TI  - [Carol Comba, 1870-1951].

PMID- 14953675
TI  - [Study on myositis ossificans progressiva with special reference to ACTH
      therapy].

PMID- 14953676
TI  - [Guenther's formula in a normal child].

PMID- 14953677
TI  - [Effect of vitamin E on sclerema neonatorum].

PMID- 14953678
TI  - [Acute pulmonary edema in newborn].

PMID- 14953679
TI  - [Commemoration of Riccardo Galeazzi].

PMID- 14953680
TI  - [Percutaneous nailing in the treatment of dislocation of the acromioclavicular
      joint].

PMID- 14953681
TI  - [Effect of the load on the development of human articular cartilage].

PMID- 14953682
TI  - [Histiocytic granuloma of the bones].

PMID- 14953683
TI  - [Treatment of forearm fractures with intramedullary nailing].

PMID- 14953684
TI  - [Effect of protein deficiency on reparatory osteogenesis in fractures;
      experimental research].

PMID- 14953685
TI  - [Intramedullary nailing in diaphyseal fractures of the forearm].

PMID- 14953686
TI  - [Tibial fractures].

PMID- 14953687
TI  - [Histiocytary granuloma and osseous pseudocysts; pathogenesis of osseous
      pseudocysts].

PMID- 14953688
TI  - [Post-traumatic Medelung's deformity and its surgery; presentation of two cases].

PMID- 14953689
TI  - [Posterior fracture of the shoulder in electroshock].

PMID- 14953690
TI  - [Second biennial of traumatic services in the Ospedale Maggiore di Bergamo].

PMID- 14953691
TI  - [Treatment of habitual dislocations of the shoulder by extension of the coracoid;
      clinical study].

PMID- 14953692
TI  - [Case of total fracture of the interocondyloid eminence in a child].

PMID- 14953693
TI  - [Epitrocheal fractures].

PMID- 14953694
TI  - [Chronic hyperplastic arthrosynovitis].

PMID- 14953695
TI  - [Anencephaly (total telencephaloschizis) and rhomboschizis with heterotopia of
      the median cerebellum; 32 day survival].

PMID- 14953696
TI  - [Various problems of comparative neurology].

PMID- 14953697
TI  - [Supraoptic commissures in the cat].

PMID- 14953698
TI  - [Modifications of cerebral circulation in shock therapy].

PMID- 14953699
TI  - [Severe involvement of the respiratory muscles in an atypical form of
      hemiplegia].

PMID- 14953700
TI  - [Electroencephalographic diagnosis of intracerebral hematoma caused by angioma].

PMID- 14953701
TI  - [Factors determining synchronism of muscle action potentials].

PMID- 14953702
TI  - [New observations on embryonic lysates in the outcome of brain diseases in
      children].

PMID- 14953703
TI  - [Physio- and psychopathology of surgery in various mental diseases].

PMID- 14953704
TI  - [EEG localization in 30 cases of intracranial tumor in relation to angiographic,
      ventriculographic & surgical control].

PMID- 14953705
TI  - [Cytochemical properties of spinal motor neuron determinates].

PMID- 14953706
TI  - [Effect of shock therapy on peripheral capillary circulation. I..].

PMID- 14953707
TI  - [Further contributions on the existence of miopragia of the capillary system in
      types of multiple sclerosis].

PMID- 14953708
TI  - [Epileptiform crises in experimental animals induced by the application of
      ultrasonic energy on the brain with dura intact].

PMID- 14953709
TI  - [New contribution on the Tramer reflex].

PMID- 14953710
TI  - [Buerger's syndrome of the brain in a patient with a carotid body neoplasia].

PMID- 14953711
TI  - [Use of chloramphenicol in neurosyphilis].

PMID- 14953712
TI  - [Agalmatorhemaphobia: the fear of speaking statues].

PMID- 14953713
TI  - [Method for the elimination of the motor component in the electroshock
      convulsion; preliminary communications].

PMID- 14953714
TI  - [Possibility of evaluating the Wedensky phenomenon in man, the reflex response
      and their significance in neuropathology].

PMID- 14953715
TI  - [Advantages of vitamin B12 combined with dinitrile succinate in dinitrile
      therapy].

PMID- 14953716
TI  - [Topography of electric rhythms in 33 cases of brain tumor].

PMID- 14953717
TI  - [Electrical activity of the brain in 8 cases of unilateral subdural hematoma].

PMID- 14953718
TI  - [Method of chloride crystallization applied to cerebrospinal fluid].

PMID- 14953719
TI  - [First determination of 2 pyridine codehydrases (DPN and TPN) in the
      cerebrospinal fluid].

PMID- 14953720
TI  - [Howell prothrombin time in cerebral vascular lesions].

PMID- 14953721
TI  - [Use of antabuse in alcoholism. II..].

PMID- 14953722
TI  - [2 cases of ageusia caused by insulin shock].

PMID- 14953723
TI  - [Preliminary considerations on the problem of melanoblastomatosis of the central
      nervous system; clinical contribution].

PMID- 14953724
TI  - [A case of myositis ossificans progressiva].

PMID- 14953725
TI  - [Behavior of nucleic acids in the nerve cell after x-irradiation].

PMID- 14953726
TI  - [Oscillography of peripheral arteries in patients subjected to electroshock and
      Sackel's insulin shock].

PMID- 14953727
TI  - [Recklinghausen's disease associated with Dupuytren's syndrome and Charcot-Marie
      disease].

PMID- 14953728
TI  - [Thalamic alterations in schizophrenics].

PMID- 14953729
TI  - [Protective action of flavonoids and P-like substances on the central nervous
      system subjected to the effects of x-rays].

PMID- 14953730
TI  - [Criticism of the Szondi test].

PMID- 14953731
TI  - [The bunch of grapes test with homogenous groups of normal subjects].

PMID- 14953732
TI  - [Results of the bunch of grapes test (Sanguireti-Sigurta modification) on a group
      of soldiers].

PMID- 14953733
TI  - [9th Convention of Italian psychologists].

PMID- 14953734
TI  - [Short wave therapy in uterine adnexa diseases].

PMID- 14953735
TI  - [Ultrasonics in the medical field; practical applications].

PMID- 14953736
TI  - [Effect of gonadotropins and prolactin on teeth in hypophysectomized rats].

PMID- 14953737
TI  - [Direct action of male sex hormones on the adrenal cortex].

PMID- 14953738
TI  - [Relation between ascorbic acid and mesenchymal mucopolysaccharide metabolism].

PMID- 14953739
TI  - [Effect of mucopolysaccharides on growth of blastomycetes].

PMID- 14953740
TI  - [Effect of hormones on glycogen synthesis by Saccharomyces].

PMID- 14953741
TI  - [Behavior of alkaline reserve in albino rats with hepatic steatosis].

PMID- 14953742
TI  - [Mechanism of convulsive phenomena from insulin in mammals and birds].

PMID- 14953743
TI  - [Apparatus for the analysis of gas, other than CO2 and O2, absorbed from blood].

PMID- 14953744
TI  - [Connections of the nervous system of coelenterates].

PMID- 14953745
TI  - [Extended muscular lesions induced by prolonged deficiency of methyl donators, in
      the rat].

PMID- 14953746
TI  - [Experimental research on the mechanism of action of sodium salicylate and drugs
      on antihyaluronidase activity].

PMID- 14953747
TI  - [Modifications of the secretory activity of the anterior pituitary induced by p
      oxypropiophenone].

PMID- 14953748
TI  - [Action exercised by pituitary hormones in receivers in relation to the
      antihormonic property of p-oxypropiophenone].

PMID- 14953749
TI  - [Electrocardiographic modifications by synthetic antihistaminics].

PMID- 14953750
TI  - [Cortisone, desoxycorticosterone and experimental tetanus].

PMID- 14953751
TI  - [Experimental intestinal infarct of allergic origin treated with cortisone or
      desoxycorticosterone].

PMID- 14953752
TI  - [Method for the determination of total iron and its artificial radioactive
      isotope Fe55 in biological materials].

PMID- 14953753
TI  - [Mechanism of action of the posterior pituitary on the passage of water through
      the skin of Rana esculenta].

PMID- 14953754
TI  - [Diaminophilia of mast cells].

PMID- 14953755
TI  - [Unusual behavior of albino rats with combined vitamin and saline deficiency].

PMID- 14953756
TI  - [Acetic acid in lymph and blood in relation to intestinal absorption and tissue
      metabolism].

PMID- 14953757
TI  - [Effect of various concentrations of 4-succinyl-amino-benzaldehyde
      thiosemicarbazone on osmotic behavior of erythrocytes].

PMID- 14953758
TI  - [Study on proliferation of erythroblasts based on mitotic index and on
      karyokinetic histogram; anemia due to leishmaniasis].

PMID- 14953759
TI  - [Chromatographic study on the composition of amino acids in total proteins in the
      normal and regenerating liver in rat; considerations on distribution of nitrogen
      alpha amines in the tissue].

PMID- 14953760
TI  - [Modification of renal function produced by intravenous sodium thiosulfate].

PMID- 14953761
TI  - [So-called mediastinal leukosarcomatosis].

PMID- 14953762
TI  - [Considerations on chronic cor pulmonale].

PMID- 14953763
TI  - [Osseous metastases of sarcoma; clinical study].

PMID- 14953764
TI  - [Biological role of primary residua and their influence in acquired specific
      tropism].

PMID- 14953765
TI  - [Hematogenous successions in juxtratracheal adenopathies in relation to their
      anatomobiological positions in the cycle of primary tuberculosis].

PMID- 14953766
TI  - [Bronchospirometry and angiopneumography; comparative study].

PMID- 14953767
TI  - [Bacteriostatic activity of soluble p. succinyl-benzaldehyde-thiosemicarbazone in
      vitro].

PMID- 14953768
TI  - [Chronological position of phlyctenular keratoconjunctivitis in primary
      tuberculosis].

PMID- 14953769
TI  - [Therapeutic problems and assistance in tuberculosis as integration of
      schermographic research].

PMID- 14953770
TI  - [Dr. Carlos Alberto Bancalari].

PMID- 14953771
TI  - [Frequency of tuberculosis in personnel of hospitals for tuberculosis].

PMID- 14953772
TI  - [Circumscribed relaxation of the diaphragm].

PMID- 14953773
TI  - [Tryptophan reaction of the cerebrospinal fluid in tuberculous meningitis].

PMID- 14953774
TI  - [Pulmonary tuberculosis in aged in dispensary].

PMID- 14953775
TI  - [Pneumococcal empyema following pneumothorax].

PMID- 14953776
TI  - [History of the Tulane University, Louisiana medical school].

PMID- 14953777
TI  - [Endamoeba histolitica infection and its clinical consequences].

PMID- 14953778
TI  - [Gastric carcinoma].

PMID- 14953779
TI  - [Ectopic pregnancy].

PMID- 14953780
TI  - [Tracheotomy in eclampsia].

PMID- 14953781
TI  - [Value of sulfonamide therapy of infantile diarrhea].

PMID- 14953782
TI  - [Prectologic diagnosis].

PMID- 14953783
TI  - [Ballistocardiography; historical review and clinical observations].

PMID- 14953784
TI  - [Cardiovascular diseases].

PMID- 14953785
TI  - [Respiratory tract diseases].

PMID- 14953786
TI  - [Allergy].

PMID- 14953787
TI  - [Endocrinology and metabolism].

PMID- 14953788
TI  - [Dermatology].

PMID- 14953789
TI  - [Effect of sleep induced with sedatives, hypnotics, and anticonvulsants on
      electroencephalography in psychomotor epilepsy].

PMID- 14953790
TI  - [Diagnostic value of pneumopericardiography; preliminary note].

PMID- 14953791
TI  - [Exeresis of the lymph nodes in cancer of distal colon; report of 2 cases].

PMID- 14953792
TI  - [Internal pleural hemorrhage as a postoperative pulmonary complication].

PMID- 14953793
TI  - [Variable vasomotor reflex reaction of the pulmonary parenchyma in the treatment
      of pulmonary hydatid cyst by Lamas and Mondino method].

PMID- 14953794
TI  - [Fistulizing tumor of the breast treated with follicular hormone].

PMID- 14953795
TI  - [Total gastrectomy in antral cancer].

PMID- 14953796
TI  - [Obliterating arterial diseases of the lower extremities; Hunter's canal syndrome
      and ring of the third abductor].

PMID- 14953797
TI  - [Surgery of three cases of Hunter's canal syndrome in chronic arterial diseases].

PMID- 14953798
TI  - [Post-traumatic reflex atelectasis; abstract of the paper presented at the
      conference of the Society with graphical documentation].

PMID- 14953799
TI  - [Shock due to acute dehydration].

PMID- 14953800
TI  - [Postoperative contralateral reflex pulmonary atelectasis in double pulmonary
      hydatid cyst].

PMID- 14953801
TI  - [Methods of tubal function tests].

PMID- 14953802
TI  - [New cases of epistaxis treated with estrogens].

PMID- 14953803
TI  - [Cardiospasm; observations on a case].

PMID- 14953804
TI  - [So-called aberrant lateral thyroid tumors].

PMID- 14953805
TI  - [New technic of surgery of hydatid cyst of the brain].

PMID- 14953806
TI  - [Atropine test in plastic surgery].

PMID- 14953807
TI  - [Pancreatic cancer; intestinal obstruction; multiple mesenteric metastases;
      radiography].

PMID- 14953808
TI  - [Penetrating duodenal ulcer].

PMID- 14953809
TI  - [Reiter's syndrome treated with aureomycin].

PMID- 14953810
TI  - [Liver function tests performed simultaneously in peripheral venous blood and in
      suprahepatic venous blood; preliminary communication].

PMID- 14953811
TI  - [Study on intracardiac pressures before and after ligation of the inferior vena
      cava].

PMID- 14953812
TI  - [Esophageal cancer; statistical data on 37 cases and 10 resections].

PMID- 14953813
TI  - PROFESOR Dr. E. Glanzmann.

PMID- 14953814
TI  - [Convulsions in children].

PMID- 14953815
TI  - [Certain statistical aspects of pneumopathies in children].

PMID- 14953816
TI  - [Case of hemolytic disease in newborn with double Rh and ABO isoimmunization].

PMID- 14953817
TI  - [Clinical application of ACTH and cortisone in children].

PMID- 14953818
TI  - [Fatal case due to nose drops].

PMID- 14953819
TI  - [Case for diagnosis].

PMID- 14953820
TI  - [Myocardium and influenza in a child; electrocardiographic study].

PMID- 14953821
TI  - [Legal and social protection of breast feeding in Uruguay; legislation in
      Vigencia].

PMID- 14953822
TI  - [Clinical application of ACTH and cortisone in pediatrics].

PMID- 14953823
TI  - [Nikolai Evgenevich Vvedenskii and his theory; 100th anniversary of his birth].

PMID- 14953824
TI  - [Role of the nervous system in the pathogenesis of hemolytic anemia].

PMID- 14953825
TI  - [Pulmonary changes in extrapulmonary cancer; paraspecific changes in cancer].

PMID- 14953826
TI  - [Pathogenesis of pulmonary sclerosis in so-called chronic nonspecific
      pneumonias].

PMID- 14953827
TI  - [Certain compensatory changes in the lungs].

PMID- 14953828
TI  - [Changes in the arterioles of the internal organs in hypertension; elastic
      hyperplasia of the intima].

PMID- 14953829
TI  - [Experimental renal hypertension in rats].

PMID- 14953830
TI  - [Experimental and pathological and anatomical study of retrograde metastases in
      rectal cancer].

PMID- 14953831
TI  - [Effect of chemical and electrical narcosis on phagocytosis].

PMID- 14953832
TI  - [Granular atrophy of the cerebral cortex in closed cranial injuries].

PMID- 14953833
TI  - [Histological investigation of the sympathetic ganglia in rabbits in repeated
      homoplastic transplantation of the adrenals].

PMID- 14953834
TI  - [Clinical aspects and Pathomorphology of rectal malignant melonomas].

PMID- 14953835
TI  - [I. R. Tarkhanov; founder of the theory on the structure of bile pigments].

PMID- 14953836
TI  - [Skin temperature and heat emission].

PMID- 14953837
TI  - [Nature of local circulatory disorders in inflamed denervated tissues].

PMID- 14953839
TI  - [In memory of Andrei Nikolaevich Magnitskii].

PMID- 14953838
TI  - [Trypan blue vital staining].

PMID- 14953840
TI  - [SEMEN Sergeevich Khalatov].

PMID- 14953841
TI  - [IOSIF Ignat'evich Burachevskii].

PMID- 14953842
TI  - [Strophanthidin-3-benzoate: cardiovascular action and therapeutic value].

PMID- 14953843
TI  - The electrocardiographic diagnosis of combined ventricular strain.

PMID- 14953844
TI  - [Procaine amide in cardiac arrhythmias].

PMID- 14953845
TI  - [Six-axis system with circular polarization: a simple method of determining the
      direction of cardiac vectors in the frontal plane; general description of the
      method].

PMID- 14953846
TI  - [Hexamethonium therapy of arterial hypertension].

PMID- 14953847
TI  - [Pheochromocytoma with paroxysmal hypertension; clinical diagnosis, results of
      surgery and determination of hormones in the tumor].

PMID- 14953848
TI  - [Malignant hypertension in a case of unilateral renal ischemia caused by
      perinephritic hematoma].

PMID- 14953849
TI  - [Acute hemarthrosis and sickle cell anemia].

PMID- 14953850
TI  - [Exchange resins; its use in congestive heart insufficiency].

PMID- 14953851
TI  - [Diabetes mellitus; auricular fibrillation; arteriosclerosis obliterans of the
      legs; gangrene of the 1st and 2d toes of the right foot; fatty degeneration of
      the liver].

PMID- 14953852
TI  - [Diphtheric myocarditis].

PMID- 14953853
TI  - [Clinico-pathological sessions: hepatic cirrhosis (portal type) with liver
      necrosis; coronary sclerosis with heart hypertrophy and myocardial fibrosis].

PMID- 14953854
TI  - [Neurological disorders in acyclic deficiency diseases].

PMID- 14953855
TI  - Human genetics as an approach to the classification of mental diseases.

PMID- 14953856
TI  - [Primary demyelinizations in the central nervous system].

PMID- 14953857
TI  - [Demyelinizing diseases of the nervous system].

PMID- 14953858
TI  - [Pseudotumoral hypertensive encephalopathy].

PMID- 14953859
TI  - [The science of psychoanalysis].

PMID- 14953860
TI  - [In Memoriam: Dr. Francoise Minkowska].

PMID- 14953861
TI  - [Desoxycorticosterone and cortisone in intoxication with diphtheria toxin].

PMID- 14953862
TI  - [Determination of sensitivity of bacteria against chemotherapeutics and
      antibiotics in bacterial infections].

PMID- 14953863
TI  - [Blockage of sensory nerves by perdural and paravertebral injection of
      alcylpolyethylenoxide ethers in guinea pigs].

PMID- 14953864
TI  - [Local anesthetic effect of several esters of the paraaminosalicylic acid].

PMID- 14953865
TI  - [Development of local anesthetics; III. V. Correlations between physicochemical
      properties & local anesthetic effects].

PMID- 14953866
TI  - [Effects of heparin on wound healing].

PMID- 14953867
TI  - [Effects of aliphatic alcohols with several OH groups and their ethers on the
      bile secretion].

PMID- 14953868
TI  - [Alpha-naphthylthiourea; testing and quantitative determination].

PMID- 14953869
TI  - [Contents of pharmaceutical plants and examination methods for tinctures made
      from plants; with contributions to an additional edition of the homeopathic
      pharmacopeia; XI. XXVIII. Berberis aquifolium, XXIX. Bryonia].

PMID- 14953870
TI  - [Identification and purification of dicumarol by production of some of its
      salts].

PMID- 14953871
TI  - [Histamine and antihistaminics; VI. 23. Clinical observations].

PMID- 14953872
TI  - [Presence, properties and chemical constitution of the cholinergic factor in
      honey].

PMID- 14953873
TI  - [A method to determine the effects of analgesics on man].

PMID- 14953874
TI  - [Evaluation of analgesics with the statistical determination of pain threshold].

PMID- 14953875
TI  - [Evaluation of analgesics with Frey's bristle method].

PMID- 14953876
TI  - [Effects of papaverine on respiratory disorders].

PMID- 14953877
TI  - [The system dye salt-carbinol base of crystal violet in vitro and vivo.
      Pharmacotherapy of oxyuriasis. IV].

PMID- 14953878
TI  - [Beta-piperidino-ethyl-4-propoxyphenylcetonhydrochloride; its local anesthetic
      use].

PMID- 14953879
TI  - [Experimental basis of therapeutic use of thyreostatic sulfur compounds. II].

PMID- 14953880
TI  - [Antibiotics except penicillin. II. Actinomycin-Aureomycin].

PMID- 14953881
TI  - [Animal experiments with Nphenyl-N-benzyl-4-amino-1-methylpiperidine after
      continuous application].

PMID- 14953882
TI  - [No80. birthday of Professor Dr. Ernst Peter Pick].

PMID- 14953883
TI  - [Tuberculosis mortality according to age].

PMID- 14953884
TI  - [On psoriasis].

PMID- 14953885
TI  - [Lucien Cornil, 1888, 1952].

PMID- 14953886
TI  - [Doctor Ch. W. T. Winckel].

PMID- 14953887
TI  - [Fear and the cult of the dead].

PMID- 14953888
TI  - [Medical massage and gymnastics].

PMID- 14953889
TI  - [Use of cryogenine tetrasulfonamide in medical practice].

PMID- 14953890
TI  - [The constitution in diseases].

PMID- 14953891
TI  - [Treatment of sprains from stretching by infiltration of sympathetic ganglion].

PMID- 14953892
TI  - [Amplitude and physiology of changes of endothoracic pressure. I. Clinical
      investigations in speleostomized patients].

PMID- 14953893
TI  - [Amplitude and physiology of changes of endothoracic pressure. II. Model
      experiments].

PMID- 14953894
TI  - [A few basic remarks to the second paper by Crecelius on superinfection therapy
      and Calmette inoculation].

PMID- 14953895
TI  - [Experiences with a modification of Maurers thoracoplasty].

PMID- 14953896
TI  - [Pulmonary damage caused by bronchography with oily iodine solutions].

PMID- 14953897
TI  - [Morphology of hydrocephalus in chronic tuberculous leptomeningitis caused by
      streptomycin].

PMID- 14953898
TI  - [Tuberculous infection in a village school room; special reference to the
      question of BCG vaccination].

PMID- 14953899
TI  - [Danger of arterial puncture].

PMID- 14953900
TI  - [Drug intoxication in combined PAS-streptomycin therapy].

PMID- 14953901
TI  - [Purpura Schoenlein-Henoch caused by dihydrostreptomycin therapy].

PMID- 14953902
TI  - [Results of lung resection in bronchiectasis].

PMID- 14953903
TI  - [Strabismus].

PMID- 14953904
TI  - [Adaptation of heart catheterization to diagnosis of acquired heart defects].

PMID- 14953905
TI  - [Cancer control in Belgium].

PMID- 14953906
TI  - [Diagnosis and therapy of bronchopneumonia due to whooping cough].

PMID- 14953907
TI  - [Surgical therapy of cardiac valve defects].

PMID- 14953908
TI  - [Entodermal cystoma].

PMID- 14953909
TI  - [Isonicotinic acid derivatives, a new remedy against tuberculosis].

PMID- 14953910
TI  - [Adie's syndrome].

PMID- 14953911
TI  - [Adrenal cortex function in the adreno-genital syndrome and in Cushing's
      disease].

PMID- 14953912
TI  - [Trauma and acute abdomen].

PMID- 14953913
TI  - [Objectives of modern medicine].

PMID- 14953914
TI  - Hygiene and diseases in Japanese prisoner of war camps in Burma and Siam.

PMID- 14953915
TI  - [The arterial blood pressure after viper bite; study based on clinical cases].

PMID- 14953916
TI  - [The contribution of Aage Bojesen in Danish pediatrics].

PMID- 14953917
TI  - [Investigations on cytochomes. I. Prosthetic group of cytochromoxydase].

PMID- 14953918
TI  - [Kallikrein inactovator in potatoes].

PMID- 14953919
TI  - [Studies on metabolism of nicotinic acid. I. Determination of nicotinic acid and
      its amide].

PMID- 14953920
TI  - [Studies on nicotinic acid metabolism. II. Metabolic relations between nicotinic
      acid, amide of nicotinic acid and their methyl derivatives in-vitro experiments
      with guinea pig and rat liver and proteus vulgaris].

PMID- 14953921
TI  - [A reducing substance in the urine present after feeding 1-rhodic acid and other
      fatty acids with similar structure].

PMID- 14953922
TI  - [Inhibition of cathepsine by butter yellow].

PMID- 14953923
TI  - [Antigenic polysaccharide from echinococcus cysts].

PMID- 14953924
TI  - [Growth of lactobacillus bifidus on synthetic media].

PMID- 14953925
TI  - [Quantitative potassium microanalysis; oxidometric potassium determination by
      tetraphenylbor-potassium].

PMID- 14953926
TI  - The intracellular components of skeletal muscle.

PMID- 14953927
TI  - The adenosinetriphosphatase activity of lipoprotein granules isolated from
      skeletal muscle.

PMID- 14953928
TI  - Studies of the bacterial cell wall. III. Preliminary investigation of the
      chemical constitution of the cell wall of streptococcus faecalis.

PMID- 14953929
TI  - Quaternary ammonium salts as inhibitors of acetylcholine esterase.

PMID- 14953930
TI  - The exocellular bacteriolytic system of soil actinomyces. III. The separation and
      characterization of the proteolytic enzymes.

PMID- 14953931
TI  - Effect of pH on the synthesis of cell carbohydrate during fermentation by Baker's
      yeast.

PMID- 14953932
TI  - The enzymic formation of acetylmethylcarbinol and related compounds.

PMID- 14953933
TI  - Acidification and polymerization of actin.

PMID- 14953934
TI  - A further contribution to the development of the flame-photometric determination
      of sodium and potassium in blood serum. II.

PMID- 14953935
TI  - [Content of amino acids which are free or in non-protein compounds present amino
      acids in the plasma of two coleopteres (Hydrophilus piceus and Leptinotarsa
      Decemlineata)].

PMID- 14953936
TI  - Interaction of ions and connective tissue.

PMID- 14953937
TI  - [New method of determination of basic amino acids in lysozyme].

PMID- 14953938
TI  - Co2-fixation in pigeon breast muscle.

PMID- 14953939
TI  - [An amino acid of the phosphatide of mycobacterium phlei].

PMID- 14953940
TI  - [Poliomyelitis; infantile paralysis or the Heine-Medin disease].

PMID- 14953941
TI  - [Some present day aspects on cancer research in the United States].

PMID- 14953942
TI  - [Biochemistry of nickel].

PMID- 14953943
TI  - The effects of cobalt, liver extract and vitamin B12 on the anemia induced by
      hypophysectomy in adult female rats.

PMID- 14953944
TI  - Red cell thickness in normals and in pernicious anemia.

PMID- 14953945
TI  - Activation of plasminogen by trypsin and plasmin.

PMID- 14953946
TI  - Separation and purification of leukocytes and platelets.

PMID- 14953947
TI  - The immediate hematologic effects of intravenous saccharated iron oxide.

PMID- 14953948
TI  - The use of thorium dioxide sol (thorotrast) in the roentgenologic demonstration
      of accessory spleens.

PMID- 14953949
TI  - Familial hypoplastic anemia with congenital abnormalities (Fanconi's syndrome).

PMID- 14953950
TI  - A case of erythremic myelosis (Di Guglielmo's anemia).

PMID- 14953951
TI  - The detection of malignant melanoma by bone marrow aspiration; a report of two
      cases.

PMID- 14953952
TI  - Aplastic anemia with platelet thrombi.

PMID- 14953953
TI  - Blood platelet counts of the golden hamster, Cricetus auratus.

PMID- 14953954
TI  - [Control of tuberculosis; achievements and future].

PMID- 14953956
TI  - The surgery of major and minor traumatic wounds including burns.

PMID- 14953955
TI  - Surgical treatment of hypertensive cardiovascular disease.

PMID- 14953957
TI  - [Intestinal diverticulosis; observations in Puerto Rico].

PMID- 14953958
TI  - [New anti-tuberculous drugs].

PMID- 14953959
TI  - [Application of the gloved needle biopsy method in pararectal tumors].

PMID- 14953960
TI  - [Acute hemorrhage due to carcinoma of the adrenal cortex].

PMID- 14953961
TI  - [Presentation of a case of Cooley's anemia in a Cuban boy; first report in Cuba].

PMID- 14953962
TI  - [Pediatric criteria].

PMID- 14953963
TI  - [Cerebral tumors in children].

PMID- 14953964
TI  - [Rheumatoid arthritis in children].

PMID- 14953965
TI  - [Determination in vitro of virulence of 38 cultures of Corynebacterium
      diphtheriae].

PMID- 14953966
TI  - [Hetrazan in the treatment of intestinal parasitic diseases].

PMID- 14953967
TI  - [Endovenous use of ACTH].

PMID- 14953968
TI  - [Corticotrophin and testosterone propionate in the treatment of nephrotic
      syndrome].

PMID- 14953969
TI  - [Generalized tuberculosis].

PMID- 14953970
TI  - [Fibrillar astrocytoma of the cerebellum].

PMID- 14953971
TI  - [Abscess of the right cerebellar hemisphere].

PMID- 14953972
TI  - [Symmetric gangrene of lower extremities in premature].

PMID- 14953973
TI  - [Considerations on tonsillectomy and on adenoidectomy in children].

PMID- 14953974
TI  - [Case of chorea with psychogenic factors].

PMID- 14953975
TI  - [Repository penicillin therapy of pinta in the Mexican peasant; clinical and
      serological survey].

PMID- 14953976
TI  - [Modern treatment and control of venereal diseases].

PMID- 14953977
TI  - [Presumably false positive serological reactions for syphilis in Central America.
      III. Relation to the content of protein, albumin and globulin in serum].

PMID- 14953978
TI  - [Modern methods of control of venereal diseases].

PMID- 14953979
TI  - [Mapharside-orvus solution in the prophylaxis of gonorrhea in women].

PMID- 14953980
TI  - [Nature and extension of the problem of yaws in the Americas].

PMID- 14953981
TI  - [Suppression of the endemoepidemic state of smallpox in Mexico].

PMID- 14953982
TI  - [Program of smallpox vaccination in Venezuela].

PMID- 14953983
TI  - [Observations on epidemic typhus in domestic guinea pigs].

PMID- 14953984
TI  - [Method of overcoming the reluctance of venereal patients to reveal their
      contacts].

PMID- 14953985
TI  - [Need for improving the professional information of nurses of venereal diseases].

PMID- 14953986
TI  - [Campaign for the eradication of yaws in Haiti].

PMID- 14953987
TI  - [Inaugural class at the department of therapeutics].

PMID- 14953988
TI  - [Effect of anesthetics on oxygen consumption and on synaptic transmission of the
      sympathetic ganglia].

PMID- 14953989
TI  - [Irreducible ileocecal invagination in an adult].

PMID- 14953990
TI  - [Right hemicolectomy performed by modified Mikulicz operation; indications].

PMID- 14953992
TI  - [Ex-president's address].

PMID- 14953991
TI  - [Winslow's hiatus hernia; spontaneous reduction].

PMID- 14953993
TI  - [Report on works presented in the Academy in 1951].

PMID- 14953994
TI  - [In memory of Alberto B. Rodriguez Egana].

PMID- 14953995
TI  - [Presidential address].

PMID- 14953996
TI  - [Treatment of goiter in the Surgical Institute Profesor Dr. Luis Guemes in 1942
      51; considerations on 183 operated cases].

PMID- 14953997
TI  - [Irreducible intestinal invagination in infants; Rutheford-Montgomery's
      operation].

PMID- 14953998
TI  - [Parathyroid osteosis; parathyroidectomy].

PMID- 14953999
TI  - [Biliary diseases in children].

PMID- 14954000
TI  - [Considerations on parotid surgery; relation of the vascular elements].

PMID- 14954001
TI  - [Arthroplasty of the hip].

PMID- 14954002
TI  - [Jejunal adenocarcinoma].

PMID- 14954003
TI  - [Postoperative thyroid hemorrhages].

PMID- 14954004
TI  - [Spinal anesthesia].

PMID- 14954005
TI  - [Calcified hepatic cyst; action of formaldehyde].

PMID- 14954006
TI  - [Irreducible intestinal invagination in infants].

PMID- 14954007
TI  - [Irreducible intestinal invagination in infants].

PMID- 14954008
TI  - [Postoperative thyroid hemorrhages].

PMID- 14954009
TI  - [Jejunal adenocarcinoma].

PMID- 14954010
TI  - [Femoral myxoma; scrapping and bone grafts, remote results].

PMID- 14954012
TI  - [Parotidectomy for postoperative parotitis].

PMID- 14954011
TI  - [Fragment wounds of the cervical esophagus].

PMID- 14954013
TI  - [Chronic phlebopathic ulcer of the leg; popliteal ligation].

PMID- 14954014
TI  - [Total gastrectomy without entero-anastomosis].

PMID- 14954015
TI  - [Treatment of goiter in the Institute Prof. Dr. Luis Guemes in 1942-51..].

PMID- 14954016
TI  - [Jejunal adenocarcinoma].

PMID- 14954017
TI  - [Spinal anesthesia].

PMID- 14954018
TI  - [Apoplexy of the gallbladder; experimental study on allergic cholecystopathies].

PMID- 14954019
TI  - [Suspected breast cancer; breast reconstruction].

PMID- 14954020
TI  - [Postoperative paralytic ileus].

PMID- 14954021
TI  - [Femoral pseudoarthrosis; acrylic prosthesis].

PMID- 14954022
TI  - [Cancer of the Vater's ampulla; duodeno-pancreatectomy].

PMID- 14954023
TI  - [Lymphatic and ovarian metastases of rectal carcinoma; rectosigmoid
      abdominoperineal extirpation].

PMID- 14954024
TI  - [Postoperative thyroid hemorrhages].

PMID- 14954025
TI  - [Spinal anesthesia].

PMID- 14954026
TI  - [Apoplexy of the gallbladder; experimental study on allergic cholecystopathies].

PMID- 14954027
TI  - [Cholangiography and prostigmine test].

PMID- 14954028
TI  - [Echinococcosis of the humerus].

PMID- 14954029
TI  - [Jejunal adenocarcinoma].

PMID- 14954030
TI  - [Postoperative thyroid hemorrhages].

PMID- 14954031
TI  - [Suspected breast cancer; breast reconstruction].

PMID- 14954032
TI  - [Considerations on diagnosis and treatment of ictus hemorrhagicus in extrauterine
      pregnancy with rupture].

PMID- 14954033
TI  - [Extirpation of parotid malignant tumor with conservation of the facial nerves].

PMID- 14954034
TI  - [Constrictive chronic pericarditis; partial pericardiectomy].

PMID- 14954035
TI  - [Recurrent shoulder dislocation; Putti-Platt procedure and results].

PMID- 14954036
TI  - [Cancer of the thoracic esophagus; Lewis's operation with two types of
      equipment].

PMID- 14954038
TI  - [Postoperative thyroid hemorrhages].

PMID- 14954037
TI  - [Considerations on diagnosis and treatment of ictus hemorrhagicus in extrauterine
      pregnancy with rupture].

PMID- 14954039
TI  - [Cholangiography in prostigmine test].

PMID- 14954040
TI  - [Internal intestinal strangulation by postoperative adhesions].

PMID- 14954041
TI  - [Post-traumatic left diaphragmatic hernia].

PMID- 14954042
TI  - [37 Years of cecosigmoidostomy for acute abdomen, pericolitis and Lane's type of
      constipation].

PMID- 14954044
TI  - [Case of ascites treated by splenectomy].

PMID- 14954043
TI  - [Internal intestinal strangulation by post-operative adhesions].

PMID- 14954045
TI  - [Epiphrenic diverticulum; transpleural surgery].

PMID- 14954046
TI  - [Post-traumatic left diaphragmatic hernia].

PMID- 14954047
TI  - [Internal intestinal strangulation by postoperative adhesions].

PMID- 14954048
TI  - [Trans-sternal pericardiectomy].

PMID- 14954049
TI  - [Carcinoma of the Vater's ampulla; duodeno-pancreatectomy].

PMID- 14954050
TI  - [Calcified cyst of the left lobe of the liver evacuated by the left hepatic duct;
      Bustos method of tamponade].

PMID- 14954051
TI  - [Calcified cyst of the left lobe of the liver evacuated by the left hepatic duct;
      Bustos method of therapy].

PMID- 14954052
TI  - [Two cases of retroperitoneal tumors].

PMID- 14954054
TI  - [Internal spontaneous biliary fistulas].

PMID- 14954053
TI  - [Retroperitoneal fibroma of the meso-appendix].

PMID- 14954055
TI  - [Pharmaceutical publications].

PMID- 14954056
TI  - [Glucoronlactone; application and preparation of injectable solutions].

PMID- 14954057
TI  - [Solubility of amidopyrine in phenazone solution].

PMID- 14954058
TI  - [Delayed dermatitis of sensitization].

PMID- 14954059
TI  - [Double perforation of the duodenum caused by peptic ulcer].

PMID- 14954060
TI  - [Bacterial nomenclature].

PMID- 14954061
TI  - [Emergency aspect of cancer of the descending colon].

PMID- 14954062
TI  - [Syphilis of the mouth].

PMID- 14954063
TI  - [Endocrine regulation of eosinophils].

PMID- 14954064
TI  - The management of the rheumatic patient.

PMID- 14954065
TI  - [Medical welfare in the Federal District].

PMID- 14954066
TI  - [The sun as a source of x-rays; cosmic politics].

PMID- 14954067
TI  - [Case of pulmonary and meningeal mycosis caused by Cryptococcus neoformans
      (torulosis)].

PMID- 14954068
TI  - [The treatment of tapeworm infection].

PMID- 14954069
TI  - [PROF Andre Dreyfus].

PMID- 14954070
TI  - [Incidence of brucellosis, especially in blood donor candidates].

PMID- 14954071
TI  - [Case of headache in hypertension].

PMID- 14954072
TI  - [New anti-tuberculosis drugs].

PMID- 14954073
TI  - [Allergy in dermatology].

PMID- 14954074
TI  - [Treatment of mucosal localizations of American cutaneous leishmaniasis by
      diaminodiphenoxy-pentane].

PMID- 14954075
TI  - [The human eye at high speeds].

PMID- 14954076
TI  - [Interdigital syphilis of the feet].

PMID- 14954077
TI  - [Brucellosis; case report].

PMID- 14954078
TI  - Endemiology of cancer of the lung in England and Wales.

PMID- 14954079
TI  - One hundred consecutive primary epithelial lung tumours.

PMID- 14954080
TI  - Neoplastic disease occurring in varicose ulcers or eczema: a report of six cases.

PMID- 14954081
TI  - Adenocarcinoma of the oesophagus and ectopic gastric mucosa.

PMID- 14954082
TI  - Cancer and essential hypertension.

PMID- 14954083
TI  - The origin and the development of the "white label" mouse strain.

PMID- 14954084
TI  - The adrenal glands in spontaneous lymphomatosis in birds.

PMID- 14954085
TI  - The latent period of co-carcinogenesis.

PMID- 14954086
TI  - Catalase poisons in relation to changes in radio-sensitivity.

PMID- 14954087
TI  - Comparison of cytological effects induced by x rays and nitrogen mustard.

PMID- 14954088
TI  - The antimitotic action of an aromatic nitrogen mustard on tissue cultures.

PMID- 14954089
TI  - The supra-vital staining of normal and malignant tissues with tetrazolium
      compounds.

PMID- 14954091
TI  - The Pityrosporum ovale.

PMID- 14954090
TI  - The phosphorus compounds of the cell nucleus.

PMID- 14954092
TI  - Itching in tension states.

PMID- 14954093
TI  - Dermatitis herpetiformis in children.

PMID- 14954094
TI  - Scleroderma with calcinosis.

PMID- 14954095
TI  - Liquefying nodular panniculitis.

PMID- 14954096
TI  - Acute disseminate lupus erythematosus treated with ACTH.

PMID- 14954097
TI  - Diagnosis: multiple self-healing epitheliomata.

PMID- 14954098
TI  - Multiple gangrene of skin.

PMID- 14954099
TI  - A. T. 10 and eucortone in psoriasis arthropathica.

PMID- 14954100
TI  - Reticulosis in infancy.

PMID- 14954101
TI  - Pemphigus vegetans; response to aureomycin therapy.

PMID- 14954102
TI  - Acanthosis Nigricans.

PMID- 14954103
TI  - Virulence to mice of Staphylococcus pyogenes: its measurement and its relation to
      certain in vitro properties.

PMID- 14954104
TI  - The action of mucin in promoting infections: the anticomplementary effect of
      mucin extracts and certain other substances.

PMID- 14954105
TI  - Investigation into the production of bacteriostatic substances by fungi;
      preliminary examination of the twelfth 100 species, all Basidiomycetes.

PMID- 14954106
TI  - The disposal and organ-distribution of radioiodinated bovine serum proteins in
      control and specifically sensitized rabbits.

PMID- 14954107
TI  - The degradation of proteins labelled with radioactive iodine in control and
      sensitized rabbits.

PMID- 14954108
TI  - Intracellular growth of phages T1 and T2.

PMID- 14954109
TI  - The effect of phage infection on the metabolic activity of the host cell.

PMID- 14954110
TI  - Suppression of the tuberculin reaction in rabbits by total body irradiation with
      x-rays.

PMID- 14954111
TI  - Titration of antisera to soluble proteins on the basis of an agglutination
      reaction: conjugation of egg albumin and chicken serum globulin to the incomplete
      Rh antibody and the subsequent use of Rh-positive cells, sensitized by such
      conjugated incomplete antibodies, to titrate antisera against egg albumin and
      chicken globulin.

PMID- 14954112
TI  - The effect of 3:5-dinitro-orthocresol on the organic phosphates of muscle.

PMID- 14954113
TI  - The persistence of resistance following the disappearance of hypersensitivity in
      guinea-pigs after vaccination with vole bacillus and BCG.

PMID- 14954114
TI  - The absorption of olive oil from the intestine in rats deprived of
      pteroylglutamic acid, biotin and pyridoxin.

PMID- 14954115
TI  - The sulphonamides: relative potencies and specificity of action.

PMID- 14954116
TI  - The evaluation of analgesic potency of drugs using thermal stimulation in the
      rat.

PMID- 14954117
TI  - The effect of analgesic drugs on the sensation of thermal pain in man.

PMID- 14954118
TI  - The effect of some oxidation products of phenothiazine on liver fluke (Fasciola
      hepatica) in vitro.

PMID- 14954119
TI  - The influence of groups in the molecule of 2:3-dihydro-3-ketobenzo-1: 4-thiazine
      on its effect on liver fluke (Fasciola hepatica) in vitro.

PMID- 14954120
TI  - The mechanism of anticurare action of certain neostigmine analogues.

PMID- 14954121
TI  - On the absence and the return of pendulum movements after contraction.

PMID- 14954122
TI  - Mechanism of methionine protection against the nephrotoxicity of polymyxin A.

PMID- 14954123
TI  - Effect of hexamethonium on the response to insulin in animals and man.

PMID- 14954124
TI  - The inhibitory action of tri-ortho-cresyl phosphate on cholinesterases.

PMID- 14954125
TI  - Accumulation of acetylcholine in brain and blood of animals poisoned with
      cholinesterase inhibitors.

PMID- 14954126
TI  - Chemotherapeutic investigations with Rous sarcoma virus.

PMID- 14954127
TI  - The roles of cortisone, desoxycorticosterone, and adrenaline in protecting
      adrenalectomized animals against heemorrhagic, traumatic, and histaminic shock.

PMID- 14954128
TI  - The quantitative determination of diffusible histamine in blood.

PMID- 14954129
TI  - Effect of denervation on amine oxidase in structures innervated by the
      sympathetic.

PMID- 14954130
TI  - The nature of cardiac sympathin in the dog.

PMID- 14954131
TI  - The secretion of the denervated adrenal medulla of the cat.

PMID- 14954132
TI  - The pharmacology of benzoylcholine.

PMID- 14954133
TI  - The pharmacological actions of 6-methyladrenaline.

PMID- 14954134
TI  - Shortening of the lesser curvature in gastric ulcer.

PMID- 14954135
TI  - The classification and staging of cancer of the larynx.

PMID- 14954136
TI  - X-ray therapy and carcinoma of the bronchus; an analysis of the effect on 218
      patients of irradiation of the primary lesion.

PMID- 14954137
TI  - An aid to the radiological diagnosis of oesophageal disease.

PMID- 14954138
TI  - Cytological investigation of bone marrow of mice after administration of
      protective agents and subsequent x radiation.

PMID- 14954139
TI  - Experimental radiotherapy of abdominal cancer. I. Factors affecting radiation
      tolerance of the abdomen in the rat.

PMID- 14954140
TI  - A generalized method of rapid dosage estimation with particular reference to 200
      KV therapy.

PMID- 14954141
TI  - The flattening of wedge isodose curves in the direction perpendicular to the
      wedge.

PMID- 14954142
TI  - Some epidemiological aspects of acute rheumatism.

PMID- 14954143
TI  - Dysplastic growth differentials in patients with psychiatric disorders studies on
      the morphology of maturity.

PMID- 14954144
TI  - Association of congenital malformation of the heart with birth rank and maternal
      age.

PMID- 14954146
TI  - Selective limitation of sibship size.

PMID- 14954145
TI  - Observations on all births (23, 970) in Birmingham, 1947. VII. Effect of changing
      family size on infant mortality.

PMID- 14954147
TI  - Birth weights of South African babies. III. Seasonal variation in birth weight.

PMID- 14954148
TI  - Relative frequencies and sex distributions of human multiple births.

PMID- 14954149
TI  - Incidence of common infections of childhood.

PMID- 14954150
TI  - Dynamics of heart failure.

PMID- 14954151
TI  - The pathogenesis of simple goiter; review.

PMID- 14954152
TI  - Acute circulatory failure during surgical operations.

PMID- 14954153
TI  - Electric convulsion therapy in treatment of prolonged stupor.

PMID- 14954154
TI  - Cortisone and tumour growth.

PMID- 14954155
TI  - Absence of response to cortisone.

PMID- 14954156
TI  - Attempt to prevent erythroblastosis foetalis by use of cortisone during
      pregnancy.

PMID- 14954157
TI  - Routine use of liquid urea medium for identifying Salmonella and Shigella
      organisms.

PMID- 14954158
TI  - A treatment of cardiac arrest.

PMID- 14954159
TI  - Cerebral thrombosis complicating pregnancy.

PMID- 14954160
TI  - IMMUNIZATION against poliomyelitis.

PMID- 14954161
TI  - MOTION sickness.

PMID- 14954163
TI  - "DEATH" and resuscitation.

PMID- 14954162
TI  - UNRESPONSIVENESS to A.C.T.H. and cortisone.

PMID- 14954164
TI  - COUVADE.

PMID- 14954165
TI  - Irregular vaginal bleeding.

PMID- 14954166
TI  - A survey of occupational problems in a neurosis centre.

PMID- 14954167
TI  - CURE of alcoholism.

PMID- 14954168
TI  - STRAFFEN.

PMID- 14954169
TI  - INFECTIOUS diseases and vital statistics.

PMID- 14954170
TI  - Use of radioactive phosphorus in mapping brain tumours at operation.

PMID- 14954171
TI  - Dynamics of heart failure.

PMID- 14954172
TI  - Rheumatic fever; some observations on A.C.T.H., cortisone, and salicylate
      therapy.

PMID- 14954173
TI  - Relation of electrolyte changes and adrenocortical activity to paralytic ileus.

PMID- 14954174
TI  - Single massive dose of vitamin B12 in untreated pernicious anaemia.

PMID- 14954175
TI  - Renal circulation and cardiac output in low-output heart failure and in
      myxoedema.

PMID- 14954176
TI  - The treatment of lumbar intervertebral disk protrusion; an assessment of
      conservative measures.

PMID- 14954177
TI  - Subacute bacterial endocarditis caused by Str. haemolyticus Group H.

PMID- 14954178
TI  - Carcinoma of cardiac portion of the stomach.

PMID- 14954179
TI  - HEART failure.

PMID- 14954180
TI  - NERVOUS control of intestinal movements.

PMID- 14954181
TI  - COELIAC disease.

PMID- 14954182
TI  - DIAGNOSIS of cancer from isolated cells.

PMID- 14954183
TI  - FOOT-and-mouth disease.

PMID- 14954184
TI  - TREATMENT of intermittent claudication.

PMID- 14954185
TI  - Nephritis-I. Aetiology, course, and diagnosis.

PMID- 14954186
TI  - SHIP surgeon.

PMID- 14954187
TI  - SIR Hugh Cairns, K.B.E., D.M., F.R.C.S.

PMID- 14954188
TI  - NOT a "hospital" within the act.

PMID- 14954189
TI  - INFECTIOUS diseases and vital statistics.

PMID- 14954190
TI  - Statistical aspects of mortality in early adult life.

PMID- 14954191
TI  - An investigation into the comparative efficacy of certain inhalants in the
      treatment of asthma.

PMID- 14954192
TI  - Asthma in childhood; a survey of the work of an asthma clinic in Hampshire.

PMID- 14954193
TI  - Lymphangitis carcinomatosa.

PMID- 14954194
TI  - Blood glutathione levels and carbohydrate tolerance during ACTH therapy.

PMID- 14954195
TI  - Streptomycin for chronic ambulant tuberculous patients.

PMID- 14954196
TI  - Acquired hypersensitivity to sodium P.A.S. streptomycin, and penicillin.

PMID- 14954197
TI  - Technique of jelly (tuberculin) testing; some further observations.

PMID- 14954198
TI  - Ununited fractures of the clavicle.

PMID- 14954199
TI  - CENTENARY of William Stewart Halsted.

PMID- 14954200
TI  - ACCIDENT proneness.

PMID- 14954201
TI  - FOOD-poisoning from cockles.

PMID- 14954202
TI  - FIGURES and flu.

PMID- 14954203
TI  - TREATMENT of penicious anaemia.

PMID- 14954204
TI  - Nephritis II. Prognosis and treatment.

PMID- 14954205
TI  - AUSTRALASIAN Medical Congress.

PMID- 14954206
TI  - WILLIAM Stewart Halsted.

PMID- 14954207
TI  - MARION Gilchrist, M.B., CM.

PMID- 14954208
TI  - C. E. Tangye, C.B.E., M.D., D.P.H.

PMID- 14954209
TI  - DEATH from nupercaine poisoning.

PMID- 14954210
TI  - INFECTIOUS diseases and vital statistics.

PMID- 14954211
TI  - Public health visits for medical students.

PMID- 14954212
TI  - [Prohibition of use of Indian hemp].

PMID- 14954213
TI  - [Low quality of potable water in the Paris region].

PMID- 14954214
TI  - [Chemical test of pregnancy; histidinuria].

PMID- 14954215
TI  - [Favorable effect of spasmophil diathesis on the development of digestive
      parasitosis].

PMID- 14954216
TI  - [In memory of Dr. Billet].

PMID- 14954217
TI  - American College of Surgeons restates principles of financial relations.

PMID- 14954218
TI  - Innovations scheduled for 1953 meetings.

PMID- 14954219
TI  - BYLAWS of the Joint Commission on Accreditation of Hospitals.

PMID- 14954221
TI  - GRADUATE training in surgery; fundamental requirements for graduate training.

PMID- 14954220
TI  - New motion pictures.

PMID- 14954222
TI  - APPROVED programs of graduate training in general surgery and in the surgical
      specialties in United States Government hospitals as of September 1, 1952.

PMID- 14954223
TI  - APPROVED programs of graduate training in general surgery and in the surgical
      specialties in civilian hospitals of the United States and in Canada as of
      September 1, 1952.

PMID- 14954224
TI  - CANCER facilities approved by College in 1952.

PMID- 14954225
TI  - [Symposium on the Rh factor].

PMID- 14954226
TI  - [The principles of the organization of the searching out of maternal
      isoimmunization].

PMID- 14954227
TI  - [The diagnosis and treatment of the hemolytic disease of the newborn].

PMID- 14954228
TI  - [The Rhesus factor (D) in the University of Louvain maternity; results of
      prenatal discovery and technic of treatment by exchange-transfusion].

PMID- 14954229
TI  - [Result of the treatment of the hemolytic disease of the newborn].

PMID- 14954230
TI  - [Discovery of maternal isoimmunization and the study of the hemolytic disease of
      the newborn at the Saint-Pierre University hospital (Pr. J. Snoeck)].

PMID- 14954231
TI  - [The organization of the struggle against the hemolytic disease of the newborn at
      the University of Liege maternity].

PMID- 14954232
TI  - [Practical organization for the discovery of isoimmunization in prenatal
      consultation].

PMID- 14954233
TI  - [Prolonged pregnancy and induction of delivery].

PMID- 14954234
TI  - [A case of ovarian pregnancy at term].

PMID- 14954235
TI  - [Presentation of a recording manometer with reduced dead space for a
      hysterosalpingography and the kymographic uterotubal perfusion].

PMID- 14954236
TI  - [The kymographic uterotubal perfusion].

PMID- 14954237
TI  - [Phlebitis of the lower left limb in the 7th month of pregnancy, treatment with
      heparin alone, cure without sequellae before delivery].

PMID- 14954238
TI  - [Two cases of the favorable course of pregnancy in spite of a serious gas
      embolism following abortifacient attempts].

PMID- 14954239
TI  - [Heparin tolerance test in vitro for the diagnosis of postpartum venous
      thromboses and for following the action of the treatment].

PMID- 14954240
TI  - [The clinical study of the effect of vitamin B1 on work].

PMID- 14954241
TI  - [An unusual muscular lesion after a normal confinement].

PMID- 14954242
TI  - [A case of uterine sarcoma in an 18 month old infant].

PMID- 14954243
TI  - [Anesthesia in the cesarean; presentation of a color film].

PMID- 14954244
TI  - [Post-menopausal uterine functional hemorrhage of medicinal origin; hematocolpos
      20 years after menopause].

PMID- 14954245
TI  - [Mole-like degeneration with dissociation of clinical and biological signs].

PMID- 14954246
TI  - [Hydatiform mole; inconsistencies between the clinical, hormonal and biological
      signs].

PMID- 14954247
TI  - [Hydatiform mole; inconsistency between the clinic and the laboratory].

PMID- 14954248
TI  - [Chorioepithelioma in first appearance; inconsistency of the clinic and the
      laboratory].

PMID- 14954249
TI  - [A newborn from a diabetic mother].

PMID- 14954250
TI  - [Retroplacental hemorrhage treated by oxytocic perfusion; considerations on the
      treatment of shock].

PMID- 14954251
TI  - [Tissue therapy in gynecology].

PMID- 14954252
TI  - [Four observations of the coexistence of intra- and extrauterine pregnancy].

PMID- 14954253
TI  - [The cervical selection of spermatozoa].

PMID- 14954254
TI  - [The effect of estrogens and progesterone in the immediate postpartum with
      respect to vaginal cytology].

PMID- 14954255
TI  - [Anhydrous mercuri-3-nitro-5, cresol-2 in the treatment of trichomonal
      vaginites].

PMID- 14954256
TI  - [A malignant ovarian tumor with ascites and hydrothorax; apropos the discussion
      of Meig's syndrome].

PMID- 14954257
TI  - [The necessity of fighting against the physiologic hypothermia of the newborn;
      fortunate effect of immediate reheating and the wisdom of this on prognosis].

PMID- 14954258
TI  - [Two cases of galactorrhea after ovarian resection].

PMID- 14954259
TI  - [Two new cases of blood disease by ABO incompatibility].

PMID- 14954260
TI  - [Twenty-five cases of hydatiform mole].

PMID- 14954261
TI  - [Two observations of ovarian cyst coexistent with the puerperal state].

PMID- 14954262
TI  - [Two cases of fatal eclampsia].

PMID- 14954263
TI  - [Hemorrhage of uncontrollable delivery; hysterectomy for hemostasis].

PMID- 14954264
TI  - [Twenty-one observations of postpartum mammary gland complications treated by
      terramycin; indications; results].

PMID- 14954265
TI  - [Three cases of podalic version by internal maneuvers with delayed birth].

PMID- 14954267
TI  - [German measles and pregnancy].

PMID- 14954266
TI  - [Oxytocic perfusions during labor].

PMID- 14954268
TI  - [Coexistence of an extrauterine pregnancy and an ovarian cyst; celioscopic
      diagnosis].

PMID- 14954269
TI  - [A case of sixfold turning of the umbilical cord].

PMID- 14954270
TI  - [Postpartum cerebral thrombophlebitis].

PMID- 14954271
TI  - [Tubular occlusions and sterility].

PMID- 14954272
TI  - [Ovarian cysts and sclerocystic ovaritis in sterility].

PMID- 14954273
TI  - [Two cases of melena with intrauterine appearance].

PMID- 14954274
TI  - [Results of several cases of intravenous anesthesia for cesarean operation].

PMID- 14954275
TI  - [A case of toxoplasmosis].

PMID- 14954276
TI  - [Contribution to the radiological study of the dilation of the milk ducts].

PMID- 14954277
TI  - [History of a nevocancer of the labia majora].

PMID- 14954278
TI  - [Surgical treatment of cancer of the uterine cervix at the preinvasive phase].

PMID- 14954279
TI  - [Some observations of round pelvis].

PMID- 14954280
TI  - [Retention of the placenta in a malformed uterus].

PMID- 14954281
TI  - [Uterine fibroma with giant intravaginal polyp].

PMID- 14954282
TI  - [Aortography with serial plates for placental localization].

PMID- 14954283
TI  - [Blood incoagulability after confinement].

PMID- 14954284
TI  - [Cerebromeningeal hemorrhage in a woman eight months pregnant].

PMID- 14954285
TI  - The relation of ancient philosophy to medicine.

PMID- 14954286
TI  - Villerme and Quetelet.

PMID- 14954287
TI  - Early neurosurgery in New York: its origin in neurology and general surgery.

PMID- 14954288
TI  - Dr. Nathan Smith Davis and the growth of Chicago medicine 1850-1900.

PMID- 14954290
TI  - FOUNDING of an International Academy of the History of Pharmacy.

PMID- 14954289
TI  - The history of laminectomy prior to 1866.

PMID- 14954291
TI  - Internal secretion of the arterial wall and regulation of blood pressure; further
      investigations.

PMID- 14954292
TI  - The effects of nitrogen mustard on the size and respiration of organs.

PMID- 14954293
TI  - Experimental non-bacterial endocarditis.

PMID- 14954294
TI  - Blood sugar tolerance tests in various types of experimental diabetes;
      contribution to the study of the role of the kidney in carbohydrate metabolism.

PMID- 14954295
TI  - Intradermoreactions with soluble bacterial fractions.

PMID- 14954296
TI  - [Major General Edgar Erskine Hume, National Delegate of the United States of
      America].

PMID- 14954297
TI  - [Relief of medical and religious personnel held with prisoners of war].

PMID- 14954298
TI  - [Results of the antimalaria campaign undertaken by the Medical Corps of the
      Spanish Army in the zone of the Protectorate of Morocco since 1943].

PMID- 14954299
TI  - [Geneva Conventions and aerial warfare].

PMID- 14954300
TI  - [Memories of General Edgar Erskine Hume].

PMID- 14954301
TI  - An evaluation of psychotherapeutic techniques.

PMID- 14954303
TI  - The function of a chaplain in psychotherapy. I. The psychiatrist's report.

PMID- 14954302
TI  - Research in the selection of psychiatrists: a second interim report.

PMID- 14954304
TI  - The function of a chaplain in psychotherapy. II. The chaplain's report.

PMID- 14954305
TI  - Death in so-called status thymicolymphaticus following insulin coma therapy.

PMID- 14954306
TI  - Problems in the approach to the neuroses and psychoses in general practice.

PMID- 14954307
TI  - The application of clinical psychological tests to a fuller understanding of
      somatic disease.

PMID- 14954308
TI  - Advances in the diagnosis of endocrine disease.

PMID- 14954309
TI  - Evaluation of acute changes in blood volume from the intravascular biological
      decay curve of P32 tagged erythrocytes.

PMID- 14954310
TI  - Studies on blood coagulation in acute myocardial infarction.

PMID- 14954311
TI  - Relationship of hypertension to the onset of coronary occlusion.

PMID- 14954312
TI  - Investigation of coagulation defects using a modified prothrombin consumption
      test.

PMID- 14954313
TI  - Criteria for the use of anti-coagulants in the treatment of acute myocardial
      infarction.

PMID- 14954314
TI  - Effect on serum lipids of weight reduction without marked fat restriction and of
      rigid fat restriction without weight reduction.

PMID- 14954315
TI  - Pilonidal sinus and cyst: an analysis of the results of surgical therapy in 229
      consecutive cases.

PMID- 14954316
TI  - Ligation of the hepatic and splenic arteries in the treatment of cirrhosis of the
      liver.

PMID- 14954317
TI  - An evaluation of vagus resection in the treatment of gastroduodenal ulcer.

PMID- 14954318
TI  - The effect of subtotal gastrectomy upon external pancreatic secretion in dogs.

PMID- 14954319
TI  - The electrogastrogram and its clinical significance.

PMID- 14954320
TI  - The maximal-size vein graft feasible in the replacement of experimental aortic
      defects, long term observations concerning the function and ultimate fate of the
      graft.

PMID- 14954321
TI  - [Toxicity of antioxidants used in preservation of fats].

PMID- 14954322
TI  - [General biological meaning of studies on cerebralization].

PMID- 14954323
TI  - [Cholinesterase content of the brain in cerebral tumors and paralysis agitans].

PMID- 14954324
TI  - [Symptomatology and physiopathology of temporal lobe diseases].

PMID- 14954325
TI  - [New investigations on universal donors].

PMID- 14954326
TI  - [Rate of fitness in the years 1913-1949 from induction to the end of the training
      year, specified according to groups of diseases].

PMID- 14954327
TI  - [Remembering Professor Dr. Robert Doerr].

PMID- 14954328
TI  - [Dr. Dr. h.c. Max Hartmann].

PMID- 14954329
TI  - [Surgery of the anterior chamber].

PMID- 14954330
TI  - [Acute hydration of the cornea during the evolution of keratoconus].

PMID- 14954331
TI  - [Localizer for sutures of retention lenses for keratoplasty].

PMID- 14954332
TI  - [Contribution to the study of the myotic action of diisopropylfluorophosphonate].

PMID- 14954333
TI  - [Study of the mode of action of retrociliary diathermy by the compression test
      with an electronic tonometer].

PMID- 14954334
TI  - [Acute exudative glaucoma].

PMID- 14954335
TI  - [Examination of the vitreous humor with the electron microscope].

PMID- 14954336
TI  - [Temporal arteritis and optic atrophy].

PMID- 14954337
TI  - [Espildora-Luque's ophthalmo-sylvian syndrome].

PMID- 14954338
TI  - [First attempts at clinical electroretinography].

PMID- 14954339
TI  - [Grouped pigmentation of the retina].

PMID- 14954341
TI  - [Treatment of amblyopia].

PMID- 14954340
TI  - [Unilateral retinitis pigmentosa].

PMID- 14954342
TI  - [Effects of cortisone in ocular diseases].

PMID- 14954343
TI  - [Cortical connections of Troxler's phenomenon].

PMID- 14954344
TI  - [Metastatic cancer of the choroid of adrenal cortical origin].

PMID- 14954345
TI  - [Physiotherapy of bilateral gliomas of the retina].

PMID- 14954346
TI  - [Cattle plague; abundance of plague virus in the nerve tissue and bone marrow of
      cattle infected with experimental cattle plague].

PMID- 14954347
TI  - [Use of BCG diagnostic test].

PMID- 14954348
TI  - [Vitamin E therapy of leprosy; neuritis and dystrophy].

PMID- 14954349
TI  - [Vitamin PP therapy in leprosy; sulfone intolerance and leprotic reactions].

PMID- 14954350
TI  - [Exanthematous fevers caused by tick bites].

PMID- 14954351
TI  - [Contagious conjunctivitis of ruminants in Indo-China].

PMID- 14954352
TI  - [Effect of chaulmoogra oil on secondary syphilitic lesions].

PMID- 14954353
TI  - [Terramycin therapy of yaws].

PMID- 14954354
TI  - [Treatment of phagedenic ulcers].

PMID- 14954355
TI  - [Filatov's tissue therapy of tropical ulcers of the legs].

PMID- 14954356
TI  - [Culture medium for protozoan parasites of the digestive tract; importance from
      the viewpoint of coprological diagnosis].

PMID- 14954357
TI  - [Terramycin therapy of amebic dysentery].

PMID- 14954358
TI  - [Direxiode therapy of amebiasis].

PMID- 14954359
TI  - [2 New species of mites in Oubangui-Chari (French Equatorial Africa): Schongastia
      oubangjiana Marc Andre 1950 and Schongastiella caeca Marc Andre 1950].

PMID- 14954360
TI  - [A species of accidentally bloodsucking Cecidomyiade].

PMID- 14954361
TI  - [Several stinging Ceratopogonidae of France and Tunisia].

PMID- 14954362
TI  - [Natural infection of the Glossina caliginea in the Douala mangrove swamps,
      Cameroons].

PMID- 14954363
TI  - [Modern technics for the rapid mounting of insects and the use of polyvinyl
      resins in microscopy].

PMID- 14954364
TI  - [Rodents of Oubangui-Chari (French Equatorial Africa); identification of several
      representative species of reservoir hosts of viruses X..].

PMID- 14954365
TI  - [Treatment of chronic elephantiasic edema of the leg by debridement of the
      annulus inguinalis].

PMID- 14954366
TI  - [Presence of Triatoma rubrofasciata (Geer) and its natural infection by
      Trypanosoma conorrhini (Donovan) in Guadeloupe and French Guiana].

PMID- 14954367
TI  - [Modality of cyclic trypanosoma infection of the Glossina caliginea of the Douala
      mangrove swamps].

PMID- 14954368
TI  - [Trypanosomiasis in Oubangui-Chari with focus at Ouham; prevention by lomidine].

PMID- 14954369
TI  - [Fatty degeneration of the liver in the Negro child].

PMID- 14954370
TI  - [Demography of French Guiana; population structure since 1946 census].

PMID- 14954371
TI  - [The most common leg ulcers in the tropics and subtropics with a description of 2
      little known ulcers, macroulcus perstans and ulcus tropicaloides].

PMID- 14954372
TI  - [Amaril symptomatology in pneumococcal hepatonephritis observed in a native of
      Oubangui-Chari; diagnostic difficulties].

PMID- 14954373
TI  - [Sulfone treatment can modify the response to the Mitsuda test in
      undifferentiated lepers].

PMID- 14954374
TI  - [The treatment of leprosy by thiosemicarbazone (T. B.)].

PMID- 14954375
TI  - [The existence in Brazzaville of the virus of infectious hepatitis of Oubangui;
      the role of mosquitoes in its transmission].

PMID- 14954376
TI  - [The murine typhus of Oubangui is serious; it deserves the name of tropical; its
      diagnosis can be difficult; it can be improved by paper electrophoresis].

PMID- 14954377
TI  - [Boutonneuse fever complicated with retinitis].

PMID- 14954378
TI  - [Behavior of serums of different domestic animals of Oubangui-Chari against the
      epidemic antigen].

PMID- 14954379
TI  - [Conclusions drawn from the use of the classic reactions for the diagnosis of
      syphilis in the normal and pathologic blood and cerebrospinal fluids in the
      native African; the reaction of V.D.R.L. and Suchet's technics].

PMID- 14954380
TI  - [The curative therapeutic effect of diamidinodiphenoxypentane on experimental
      infection with Trypanosoma gambiense of the rat. II. The behavior of animals
      previously cured of trypanosomiasis by the delayed inoculation of the homologous
      trypanosome].

PMID- 14954381
TI  - [The crystallization of blood ingested by the Reduviidae, genus Triatoma
      infestans (Klug (1834), T megista (Burmeister 1835), T rubrovaria (Blanchard
      1843), and T brasiliensis (Neiva 1911)].

PMID- 14954382
TI  - [Tetanus after quinine].

PMID- 14954383
TI  - [Tuberculin reaction in A. O. F].

PMID- 14954384
TI  - [Instructions in leprous reactions].

PMID- 14954385
TI  - [The possibilities of diffusion of a strain of sporadic typhus of endemic type].

PMID- 14954386
TI  - [The fundus of the eye in human trypanosomiasis].

PMID- 14954387
TI  - [Simplified nomenclature of the African mollusk vectors of bilharziasis;
      suggestions for an analytical discussion for a future classification].

PMID- 14954388
TI  - [Glossina palpalis of the costal zones in the mangroves of Douala (Cameroun
      Francais)].

PMID- 14954389
TI  - [Epitheliosarcoma of the scalp].

PMID- 14954390
TI  - [Company Medical Sciences Madagascar].

PMID- 14954391
TI  - [The first attempt of treatment of plague with chloromycetin].

PMID- 14954392
TI  - [The prevention of plague by means of synthetic organic insecticides in
      Tananarive; preliminary results].

PMID- 14954393
TI  - [Natural plague infection in guinea pigs domestic and rabbits; the presence of
      guinea pigs in the rabbit hutch disperses rats].

PMID- 14954394
TI  - [Experimental investigation on epidemiological role of green vegetables in
      poliomyelitis].

PMID- 14954395
TI  - [Studies on the effect of specific and non-specific factors on the velocity of
      diffusion of anti-Vi bacteriophage].

PMID- 14954396
TI  - [Studies on the efficiency of methods of separation of bacteriophage anti-Vi from
      bacterial suspensions].

PMID- 14954397
TI  - [Effect of biological purification of sewage on bacteriophage anti-Vi content].

PMID- 14954398
TI  - [Studies on seasonal variations of pollution of sea water in the Gulf of Gdansk].

PMID- 14954399
TI  - [Investigations on the incidence and origin of Erysipelothrix rhusiopathiae in
      sea fish and fishery workers].

PMID- 14954400
TI  - [Microcultures of Mycobacterium tuberculosis obtained on the synthetic medium
      DGK].

PMID- 14954401
TI  - [Observations on the course of pseudotuberculosis in laboratory rodents with
      special reference to factors favorable to enzootic conditions].

PMID- 14954402
TI  - [Studies on agglutination of Pasteurella septica by anti-Brucella sera].

PMID- 14954403
TI  - [Four cases of congenital toxoplasmosis in Gdansk].

PMID- 14954404
TI  - [Age and number of generations of Anopheles maculipennis atroparvus v. Thiel
      populations in the Gdansk region in 1949-50].

PMID- 14954405
TI  - [Principles of culture of Rickettsia prowazeki by Weigl's method].

PMID- 14954406
TI  - [Actinometric studies].

PMID- 14954407
TI  - FIRST international symposium on chemical microbiology: micorbial growth and its
      inhibition.

PMID- 14954408
TI  - Reaction patterns in bacterial metabolism.

PMID- 14954409
TI  - [Effect of heat on liberation of nucleic acid by bacterial cells].

PMID- 14954410
TI  - Vitamin-B-group substances especially folic acid and B12 in the metabolism of
      micro-organisms.

PMID- 14954411
TI  - [Specific inductors and inhibitors in the biosynthesis of an enzyme; beta
      galactosidase of Escherichia coli].

PMID- 14954412
TI  - The lag phase in the growth curve of pasteurella pestis.

PMID- 14954413
TI  - Studies on aeration. I.

PMID- 14954414
TI  - Recent advances in penicillin fermentation.

PMID- 14954415
TI  - Chemistry of terramycin.

PMID- 14954416
TI  - The concept of biological potency as applied to closely related antibiotics.

PMID- 14954417
TI  - Antibiotics as animal-growth stimulants.

PMID- 14954418
TI  - Antifungal antibiotics.

PMID- 14954419
TI  - Some aspects of microbial resistance to streptomycin.

PMID- 14954420
TI  - Genetic analysis of drug-resistance.

PMID- 14954421
TI  - [Structural relations of natural substances].

PMID- 14954422
TI  - Physiological background to microbial inhibition.

PMID- 14954423
TI  - [Bacteriophage cycle in lysogenic bacteria].

PMID- 14954424
TI  - Observations on Penicillium chrysogenum in submerged culture. 1. Mycelial growth
      and autolysis.

PMID- 14954425
TI  - Observations on Penicillium chrysogenum in submerged culture. 2. Cytological and
      cytochemical investigations.

PMID- 14954426
TI  - [Allocution by Claude Gautier, president, commemorating the death of Jules
      Tinel].

PMID- 14954427
TI  - [Cortisone and ACTH therapy of Bouillaud's diseases; primary results].

PMID- 14954428
TI  - [Granulogram in cancer of the lungs].

PMID- 14954429
TI  - [Landry's syndrome and myocardial insufficiency in malignant diabetic acidosis;
      spectacular action of potassium chloride].

PMID- 14954430
TI  - [A case of tetanus treated by hibernation].

PMID- 14954431
TI  - [Arterial lesions in meningeal spaces in tuberculous meningitis].

PMID- 14954432
TI  - [Cutaneous sensitivity to PAS (reaction following its ingestion)].

PMID- 14954433
TI  - [Two new cases of acquired myxedema in adults following intramuscular injection
      of iodated oil].

PMID- 14954434
TI  - [Edematous syndrome in pseudo-sprue].

PMID- 14954435
TI  - [Changes in electroencephalogram during the course of cortisone and ACTH
      therapy].

PMID- 14954436
TI  - [Pre-pubertal Basedow's diseases].

PMID- 14954437
TI  - [Postoperative hydro-electrolytic disequilibrium; importance of potassium level].

PMID- 14954438
TI  - [Pyelorenal malformations in chronic nephritis].

PMID- 14954439
TI  - [142 cases of tuberculosis affecting tissues or organs from the middle
      germinative layer (mesoderm and mesenchyme)].

PMID- 14954440
TI  - [Variations in kidney tests in standing and reclining positions].

PMID- 14954441
TI  - [Myxedema of central origin; significance of thyreostimuline test].

PMID- 14954442
TI  - [Treatment of lipoid nephrosis with adrenocorticotropic hormone (ACTH)].

PMID- 14954443
TI  - [Diaphragmatic hernia and recurrent venous thromboses].

PMID- 14954444
TI  - [Variations in the blood haptoglobin index during the various stages of
      syphilis].

PMID- 14954445
TI  - [Comparison of the variations in the blood haptoglobin index and the erythrocyte
      sedimentation rate in syphilis].

PMID- 14954446
TI  - [Latent deficiency syndrome with parotitis in a case of chronic bacillary
      dysentery].

PMID- 14954447
TI  - [Abnormal electroencephalographic findings in patients with Addison's disease;
      reversal during treatment].

PMID- 14954448
TI  - [Cinedensigraphic examination of the intrathoracic arterial circulation; its
      applications in the diagnosis of pulmonary cancers and tumors of the
      mediastinum].

PMID- 14954449
TI  - [Hippocratic fingers with joint disease, of pulmonary origin; effect of treatment
      with cortisone].

PMID- 14954450
TI  - [Cases of acute tuberculosis (meningeal, splenic and lymphatic) during ACTH
      therapy of two cases of lymphoblastic leukosis].

PMID- 14954451
TI  - [Walking disorders resembling pithiatism; cerebral atrophy].

PMID- 14954452
TI  - [Electroencephalographic modifications of the epileptic type in a patient with
      nervous complications resembling pithiatism].

PMID- 14954453
TI  - [Methylandrostenediol: physiological effects; preliminary therapeutic results].

PMID- 14954454
TI  - [A hitherto unknown aspect of the nervous complications of varicella; neuralgic
      forms].

PMID- 14954455
TI  - [Puncture biopsy of the liver complicated by peritonitis followed by pleural
      biliary effusion].

PMID- 14954456
TI  - [Vasomotor disorders of the extremities in a patient with splenomegaly;
      spectacular improvement after splenectomy].

PMID- 14954457
TI  - [Two cases of malignant giant follicular lymphoma (Brill-Symmers disease)].

PMID- 14954458
TI  - [Occipital angioma with cerebromeningeal hemorrhage; surgery; cure with temporary
      visual agnosia].

PMID- 14954459
TI  - [Nervous manifestations of Vaquez' disease].

PMID- 14954460
TI  - [Treatment of petit mal epilepsy with dimethylethyloxazolidinedione].

PMID- 14954461
TI  - [Sarcomatous degeneration of Paget's disease; four new cases].

PMID- 14954462
TI  - [Angina and heparin].

PMID- 14954463
TI  - [Clinical and hemodynamic study of the phenomenon of hepato-jugular reflex].

PMID- 14954464
TI  - [Phases of Korotkoff's sounds in hypertensive patients].

PMID- 14954465
TI  - [Diffuse papillary glandular cholecystitis].

PMID- 14954466
TI  - [A case of Lobstein's disease associated with Glanzmann's hereditary familial
      thrombasthenia].

PMID- 14954467
TI  - [Sexual repercussions from gastrectomy for ulcer].

PMID- 14954468
TI  - [A case of writer's cramp cured by trihexyphenidyl].

PMID- 14954469
TI  - [Intradermal administration of ACTH].

PMID- 14954470
TI  - [Implants of thyroid gland in the treatment of chronic rheumatism].

PMID- 14954471
TI  - [Angiographic study of the superior vena cava system in cases of mediastinal
      tumors].

PMID- 14954472
TI  - [Hypoplastic myelosis in an epileptic woman treated with phenylacetylurea in
      combination with gardenal and benzedrine].

PMID- 14954473
TI  - [Serious ulcero-hemorrhagic colorectitis treated sucessfully with ACTH;
      appearance of serofibrinous pleurisy fifty days after cessation of treatment].

PMID- 14954474
TI  - [A case of complete but temporary resistance to cortisone].

PMID- 14954475
TI  - [Malignant lupus erythematosus; Hargrave cells in samples of concentrated blood
      and positive results with Haserick's plasma-test].

PMID- 14954476
TI  - [Interpretation of the processes involved in abortive pneumonia].

PMID- 14954477
TI  - [Subacute encephalomyelitis and benign inoculation lymphoreticulosis (cat-scratch
      disease)].

PMID- 14954478
TI  - [Gynecomastia and neurological disorders].

PMID- 14954479
TI  - [Hypothalamic obesity after surgery of the pituitary gland].

PMID- 14954480
TI  - [Angiographic study of compression of the superior vena cava and its tributaries
      in patients with mediastinal lesions].

PMID- 14954481
TI  - [Physiopathological study of the pulmonary circulation in a case of Eisenmenger
      complex].

PMID- 14954482
TI  - [Arteriovenous aneurysm of the lung; lobectomy; cure].

PMID- 14954483
TI  - [The time required for injected bromsulphalein to appear in the bile: its value
      in the diagnosis of incomplete retention jaundice and in anicteric obstruction of
      the common bile duct].

PMID- 14954484
TI  - [Considerations on the syndrome of enlarged left auricle, complete arrhythmia and
      fever].

PMID- 14954485
TI  - [Metabolism of iron in the descendants of patients with bronze cirrhosis].

PMID- 14954486
TI  - [Phlebitis caused by mumps].

PMID- 14954487
TI  - [A case of permanent arterial hypertension with serious cardiac localization
      treated and improved by surgery (adrenalectomy and sympathectomy].

PMID- 14954488
TI  - [Bronchial tumor caused by Scopulariopsis americana, an early indication of
      Gilchrist's disease].

PMID- 14954489
TI  - Adenosinetriphosphatase study during rat liver damage. I. ATP-ase activity of rat
      liver during regeneration after partial hepatectomy.

PMID- 14954490
TI  - A rapid method for the determination of sodium in serum.

PMID- 14954491
TI  - The effects of some dietary derived lipids and fat soluble vitamins on rat serum
      tributyrinase and alkaline phosphatase.

PMID- 14954492
TI  - Acute experimental heart failure produced by intravenous gum acacia infusion.

PMID- 14954493
TI  - Cardiotonic activity of certain steroids and bile salts.

PMID- 14954494
TI  - [The effect of fasting on the development of experimental arthritis].

PMID- 14954495
TI  - The occurrence of zinc in the human prostate gland.

PMID- 14954496
TI  - The effect of temperature on the circulation of the isolated perfused rabbit ear.

PMID- 14954497
TI  - Heparinase. II. Distribution of enzyme in various tissues and its action on
      natural heparins and certain synthetic anticoagulants.

PMID- 14954498
TI  - Glucose utilization in blood cells surviving storage at -79 degrees C.

PMID- 14954499
TI  - The cerebral cortex and locomotor activity in rats.

PMID- 14954500
TI  - Systems of shared meaning as affecting the structure of personality.

PMID- 14954501
TI  - The dependence of binocular fusion on timing of peripheral stimuli and on central
      process.

PMID- 14954502
TI  - A study of the existence of certain prejudices in the middle years of the adult.

PMID- 14954503
TI  - Presidential address.

PMID- 14954504
TI  - Some observations on sickness insurance in Europe.

PMID- 14954505
TI  - The health centre in Britain.

PMID- 14954506
TI  - International immunization procedures.

PMID- 14954507
TI  - Tuberculin patch testing survey of the rural school population in southwestern
      Manitoba.

PMID- 14954508
TI  - A new Salmonella type: S. Chicago.

PMID- 14954509
TI  - CANADIAN Public Health Association 1951-1952. Part II.

PMID- 14954510
TI  - [Massive or fractional digitalization of congestive heart failure with auricular
      fibrillation].

PMID- 14954511
TI  - The surgical treatment of mitral stenosis.

PMID- 14954512
TI  - The acute effect of nicotine recorded in electrocardiograms in rabbits.

PMID- 14954513
TI  - Hypoproteinemia in intractable congestive failure and the use of plasma infusions
      ints treatment. A case report.

PMID- 14954514
TI  - [Histology and histogenesis in Chirocephalus diaphanus Prev. Phyllopode,
      Anostrace].

PMID- 14954515
TI  - [The development of Stigmatea geranii].

PMID- 14954516
TI  - [The embryology of the Lemnaceae; observations on Lemna minor L..].

PMID- 14954517
TI  - [New investigations on the sporangial and parasporangial organs in the ferns. I.
      Paraphyses and sorus in Polypodium nigrescers Bl..].

PMID- 14954518
TI  - [Photoelectric anisotrophy measurements of the giant chromosomes of Drosophila].

PMID- 14954519
TI  - [Histology of the digestive apparatus of the Pterotracheidae (Heteropodes)].

PMID- 14954520
TI  - [Meiosis and the induction of colchicine polyploidy in Amblystegium riparium].

PMID- 14954521
TI  - The golgi substance.

PMID- 14954522
TI  - Calcium, phosphorus, and nitrogen of nursery school lunches.

PMID- 14954523
TI  - Studies on the body size of North American children of Mexican ancestry.

PMID- 14954524
TI  - A preliminary study of developmental trends in sociempathy; accuracy of
      perception of own and others' sociometric status.

PMID- 14954525
TI  - Sociographic analysis of sociometric valuations.

PMID- 14954526
TI  - Age-mate acceptance and indices of peer status.

PMID- 14954527
TI  - Results of the surgical treatment for mitral stenosis; analysis of one hundred
      consecutive cases.

PMID- 14954528
TI  - The pathogeneis of spontaneous cardiac rupture.

PMID- 14954529
TI  - The action of SKF 688A (phenoxy-ethyl derivative of dibenamine) upon certain
      functions of the sympathetic nervous system in man.

PMID- 14954530
TI  - Observations on the fate of ingested cholesterol in man.

PMID- 14954531
TI  - Deposition and disappearance of digitoxin from the tissues of the rat, rabbit,
      and dog after parenteral injection.

PMID- 14954532
TI  - Correlation of serum potassium concentrations with the blood pressure in rats fed
      a potassium-deficient ration.

PMID- 14954533
TI  - Pressor effects of epinephrine, norepinephrine and desoxycorticosterone acetate
      weakened by sodium withdrawal.

PMID- 14954534
TI  - The measurement of the Q-T interval of the electrocardiogram.

PMID- 14954535
TI  - The Nickerson ballistocardiogram in arteriosclerotic heart disease with and
      without congestive failure.

PMID- 14954536
TI  - The ballistocardiogram in myocardial infarction: a study of one hundred cases.

PMID- 14954537
TI  - The ballistocardiogram in a free clinic.

PMID- 14954538
TI  - Surgical treatment of coarctation of the aorta in a ten week old infant: report
      of a case.

PMID- 14954539
TI  - The origin of the variations of body impedance occurring during the cardiac
      cycle.

PMID- 14954540
TI  - Traumatic heart disease; nonpenetrating injuries.

PMID- 14954541
TI  - AMERICAN Society for the Study of Arteriosclerosis; program of the sixth annual
      meeting.

PMID- 14954542
TI  - [Breast cancer and testosterone].

PMID- 14954543
TI  - [Surgical technique in the treatment of uterus biocornis].

PMID- 14954544
TI  - [Certain observations on complicated fractures of the cranial valut].

PMID- 14954545
TI  - [Direct fractures of the orbit radiating to the anterior and middle part of the
      cranial base].

PMID- 14954546
TI  - [Bone grafts in the treatment of osteoarticular tuberculosis in adults].

PMID- 14954547
TI  - [Allergy and surgery].

PMID- 14954548
TI  - [Preoperative care in ocular surgery].

PMID- 14954549
TI  - [Address at the 10th anniversary of the Academy of Surgery of Mexico, 10 June,
      1952].

PMID- 14954550
TI  - [General diagnosis of chronic enteritis].

PMID- 14954551
TI  - [Maternal mortality].

PMID- 14954552
TI  - [Biological slant of psychiatry; about our book psychiatric physiopathology].

PMID- 14954553
TI  - [Lymph node perforation].

PMID- 14954554
TI  - [Diagnosis of congenital dislocation of the hip].

PMID- 14954555
TI  - [Infantile dystrophies].

PMID- 14954556
TI  - [Pathology of Don Fernando the Catholic].

PMID- 14954557
TI  - [Horseshoe kidney].

PMID- 14954558
TI  - [Etiological treatment of cirrhosis].

PMID- 14954559
TI  - [Lutein and theca cell ovarian tumors].

PMID- 14954560
TI  - [Ligature of the inferior vena cava; indications and results; presentation of a
      clinical case].

PMID- 14954561
TI  - [Glomus tumors; presentation of two clinical cases].

PMID- 14954562
TI  - [Recurrent allergic periarthritis of the shoulder caused by sensitization to milk
      and cheese].

PMID- 14954563
TI  - [Diencephalohypophysial forms of Basedow's disease].

PMID- 14954564
TI  - [Elimination and formation of histamine in the feces of normal and allergic
      subjects].

PMID- 14954565
TI  - [Role of cytochrome C in physiopathology and its therapeutic applications].

PMID- 14954566
TI  - [Peculiar clinical and epidemiological aspects of diseases of the lungs caused by
      viruses and rickettsiae].

PMID- 14954567
TI  - [Interesting publications in Spanish medical literature for 1949].

PMID- 14954568
TI  - [The organic field in pulmonary tuberculosis].

PMID- 14954569
TI  - [Therapy of chilblains and frostbite].

PMID- 14954570
TI  - [Histamine in tissue reactions of pulmonary tuberculosis].

PMID- 14954571
TI  - [Anesthesia in surgery; cleft palate and harelip].

PMID- 14954572
TI  - [Determination of amount of prothrombin in the blood].

PMID- 14954573
TI  - [The erythrocytic elliptocytosis index during pregnancy].

PMID- 14954574
TI  - [The electrocardiogram before, during and after delivery].

PMID- 14954575
TI  - [Post-operative occlusions after gynecological surgery].

PMID- 14954576
TI  - [Two cases of multiple sclerosis in pregnancy].

PMID- 14954577
TI  - [Breus' mole expelled at term of pregnancy].

PMID- 14954578
TI  - [Considerations on primary cutaneous tuberculosis].

PMID- 14954579
TI  - [Determination of basal metabolism in sleep induced with tio-barbiturates].

PMID- 14954580
TI  - [Statistical data on malignant tumors in children in pediatric clinics in Siena
      and in Modena in 1936-51].

PMID- 14954581
TI  - [Experimental studies on the effect of paraaminobenzoic acid on gentisic acid in
      the blood and on its urinary elimination in normal children].

PMID- 14954582
TI  - [Relations between testosterone and cortisone in their effects on certain
      receptor organs].

PMID- 14954583
TI  - [Synergisms in the toxins of Fusarium lycopersici Sacc].

PMID- 14954584
TI  - [The polarographic determination of the valence of arsenic in the warm waters of
      Bourboule].

PMID- 14954585
TI  - [Pollination in several species belonging to the genera, Linum, Cymbalaria and
      Phaseolus].

PMID- 14954586
TI  - [The effects of warming on the mitochondria in the meristem of the roots of
      Allium cepa grown at 0 degrees C].

PMID- 14954587
TI  - [The relative diagnostic value of crossed antibiosis between antibiotic
      Streptomyces].

PMID- 14954588
TI  - [Conditioning the sexual cycles in the sparrow by natural and artificial light;
      the necessity of temporary darkness].

PMID- 14954589
TI  - [The role of bivalent cations in the induction of the development of prophage by
      reducing agents].

PMID- 14954590
TI  - [The local transfer of allergy to melitin].

PMID- 14954591
TI  - [Single total body x-ray of the guinea pig principal biological effects].

PMID- 14954592
TI  - [Prevention of hemorrhagic shock by hypothermy associated with autonomic
      stabilization].

PMID- 14954593
TI  - [Reaction of decapitated insects to volatile odors].

PMID- 14954594
TI  - [The physiologic role of sinigroside from the black mustard (Brassica nigra Koch
      Cruciferes)].

PMID- 14954595
TI  - [Cellular dedifferentiation and cleavage of mitochondria during the evolution of
      nursing cells of the galls in the bramble (Diastrophus Rubi Htg.)].

PMID- 14954596
TI  - [The stimulation of exchanges in the rabbit by feeding and the restrictions
      applied to the idea of the specific dynamic action in this species].

PMID- 14954597
TI  - [Free amino acids of fish blood; chromatography].

PMID- 14954598
TI  - [The experimental production of twins in the embryo of a salmon].

PMID- 14954599
TI  - [Modification of the basophilia of the liver cell in the pregnant rabbit].

PMID- 14954600
TI  - [The influence of variations in salinity of the external environment on epigeous
      and cavernous crustacea. I. The intensity of respiratory exchanges].

PMID- 14954601
TI  - [A new method for obtaining and preserving powdered organs, intended for
      therapeutic use, by the use of low temperatures, dessiccation and vacuum].

PMID- 14954602
TI  - [Structure of proteins and the action of arginase on the products of their
      partial hydrolysis].

PMID- 14954603
TI  - [The formation of fermentation inhibitory substances by Botrytis cinerea].

PMID- 14954604
TI  - [Presence in French sulfurated waters of sulfate reducing bacteria and of a
      proteolytic variety of Actinobacterium israeli: A israeli var. liquefaciens (nov.
      sp.)].

PMID- 14954605
TI  - [The action of hyaluronidase on the curative value of antivenom serum].

PMID- 14954606
TI  - [An observed phenomenon during the local transfer of allergy to melitin].

PMID- 14954607
TI  - [The electroencephalographic modifications induced by the intravenous injection
      of novocaine in serious cranial traumata].

PMID- 14954608
TI  - [Ectrodactylia and syndactylia in Rana temporaria].

PMID- 14954609
TI  - [A histological study of the action of depolymerizing enzymes on dental ivory].

PMID- 14954610
TI  - [New investigations on the balanced diet and vitamin B1 requirements of the
      pigeon].

PMID- 14954611
TI  - [Attempt of early diagnosis of jaundice and flaccidity in Bombyx mori by
      chromatographic blood analysis].

PMID- 14954612
TI  - [On the mechanism of action of isochondodendrine sulfate].

PMID- 14954613
TI  - [The action of serum globulins and ethyl alcohol on the adrenal ascorbic acid].

PMID- 14954614
TI  - [Symptomatology and pathogenesis of the edematous syndrome produced by dextran in
      the rat].

PMID- 14954615
TI  - [The inhibitory action of promethazine and adrenalin on dextran edema in the
      rat].

PMID- 14954616
TI  - [The presence of segments of stoppage and of glomi in the wall of dilated
      bronchi].

PMID- 14954617
TI  - [The adrenal cortex in the field mouse (Microtus arvalis P) and its modifications
      after castration].

PMID- 14954618
TI  - [A new technic for the production of early syphilitic acute orchitis in rabbits].

PMID- 14954619
TI  - [Infiltrates of polynuclear eosinophils in the connective tissue during acute
      formal stress in animals].

PMID- 14954620
TI  - [The influence of different p-aminosalicylic acid salts on protein and glucose
      metabolism in tuberculosis].

PMID- 14954621
TI  - [New data on the lability of acid-alcohol resistance of some mycobacteria].

PMID- 14954622
TI  - [The upper limits of size permitting passage of mineral particles from the
      peritoneal cavity through the diaphragm to the mediastinal lymph nodes].

PMID- 14954623
TI  - [Effects of methionine and cystine on the thyroid and on the pituitary
      thyrotropic activity in rats partially protein deficient].

PMID- 14954624
TI  - [The left ventricle, site of anoxic inversion of the T-wave; asphyxia].

PMID- 14954625
TI  - [The emetic drugs during barbituric anesthesia].

PMID- 14954626
TI  - [The transformation of thyroxin in the peripheral tissues from its circulating
      form of its active sensitizing form].

PMID- 14954627
TI  - [The effect of ultracentrifugation on serum content of antitreponema immobilisins
      and anti-typhoid agglutinins and anti-sheep hemolysins].

PMID- 14954628
TI  - [The action of testosterone propionate on the sexual behavior of the normal adult
      male rat].

PMID- 14954629
TI  - [The non-specific protein nitrogen fixation by cardiolipin antigens in normal and
      syphilitic sera].

PMID- 14954630
TI  - [Mercaptopyruvic acid and liver protection in carbon tetrachloride intoxication].

PMID- 14954631
TI  - [The effect of mercaptopyruvic acid on liver glycogen in carbon tetrachloride
      poisoning].

PMID- 14954632
TI  - [Checking action of cortisone on compensating renal hypertrophy in rats].

PMID- 14954633
TI  - [Studies on mammalian fertilization; the ascent of sperm in the genital tract of
      the ewe].

PMID- 14954634
TI  - [The study of certain enzymatic properties of Mycobacterium tuberculosis and
      paratuberculosis bacilli].

PMID- 14954635
TI  - [A study on the antibiotic power of paraaminosalicylic acid on Mycobacterium
      tuberculosis. The toxicity of paraaminosalicylic acid proper to Koch's bacillus].

PMID- 14954636
TI  - [The primary ureter of the frog develops posteriad from a blastema near the
      pronephros; an experimental demonstration].

PMID- 14954637
TI  - [Experimental data on hyperazotemia autodigestion of blood].

PMID- 14954638
TI  - [Certain results obtained by a statistical method of analysis of the
      electroencephalogram].

PMID- 14954639
TI  - [Measure of the electric resistance of the skin and of the psychogalvanic reflex
      during different physiologic states by an electronic method].

PMID- 14954640
TI  - [Experimentation with the longitudinal section of the blastula of Leptinotarsa
      (Insecta, Col.)].

PMID- 14954641
TI  - [The effect of low temperatures (liquid air) on the ameba Entomeba invadens].

PMID- 14954642
TI  - [The glandual system of Lanice conchilega (Pallas) and its histochemical
      aspects].

PMID- 14954643
TI  - [Hemagglutinins anit-A and anti-B in breast milk; their role in the pathology of
      the newborn].

PMID- 14954644
TI  - [The study of the sensitivity and specificity of the test of trypsin treated
      erythrocytes for detection of anti-rhesus agglutinins].

PMID- 14954645
TI  - [Modifications of the nyctohemeral rhythms of diuresis and urinary excretion of
      17-ketosteroids by reversal of the normal rhythm of water intake].

PMID- 14954646
TI  - [Experimental contribution to the problem of the origin of the spinal and
      sympathetic ganglia in the chick embryo].

PMID- 14954647
TI  - [The experimental intersexuality of embryonic duck gonads in vitro].

PMID- 14954648
TI  - [Hormone action on the sexual differentiation of the duck syrinx in vitro].

PMID- 14954649
TI  - [Experimental demonstration of the migration of regeneration cells in
      regeneration of limbs in Triton cristatus].

PMID- 14954650
TI  - [The enzymatic activity of the autolysates of the male and female Mullerian ducts
      of the chick embryo].

PMID- 14954651
TI  - [Clot retraction in man studied with the aid of a new technic].

PMID- 14954652
TI  - [The biochemical constitution of bone after cutting the sciatic nerve in rats].

PMID- 14954653
TI  - [Evolution of the specific activity of phospholipids of the adipose tissue in the
      rat after administration of radiophosphorus].

PMID- 14954654
TI  - [Thoracic growth in Calliptamus Okbaensis].

PMID- 14954655
TI  - [The endocrine glands of the non-fasting hypophysioprivic toad].

PMID- 14954656
TI  - [Hepatic ascorbic acid in the hypophysectomized rat].

PMID- 14954657
TI  - [Intraprostatic grafts of testis, ovary and adrenal in castrated male rats].

PMID- 14954658
TI  - [The histological process of thyroid intrasplenic autografts in thyroidectomized
      rats].

PMID- 14954659
TI  - [The action of mammalian pituitary hormones on toads and frogs].

PMID- 14954660
TI  - [The action of corticotrophin, cortisone and desoxycorticosterone on hemorrhagic
      shock].

PMID- 14954661
TI  - [The sensitivity of Corynebacteria of man to antibiotics].

PMID- 14954662
TI  - [Prevention and negation of ultraviolet iysogenic induction by heating].

PMID- 14954663
TI  - [The effect of a transitory bacteriostatic phase in Staphylococcus aureus on
      lysogenesis induced by ultraviolet rays].

PMID- 14954664
TI  - [Distribution of type II and III bacteriophages in normal and pathologic feces].

PMID- 14954665
TI  - [Parallel research in the feces of strains producing colicine E and K and of type
      II and III bacteriophages].

PMID- 14954666
TI  - [The pharmacology of procaine amide hydrochloride].

PMID- 14954667
TI  - [The cellular localization of the gonadotropic hormones in the anterior lobe of
      the pituitary in rats].

PMID- 14954668
TI  - [The mechanism of action of prolactin on the mammary gland in the rat].

PMID- 14954669
TI  - [Attempt to stabilize glycerinated vaccine pulp treated with weak concentration
      of formol; action of cysteine and lanolin; importance of pH].

PMID- 14954670
TI  - [Stabilization of glycerinated and formulated vaccine pulp with phosphate buffer
      solutions and with gelatin].

PMID- 14954671
TI  - [Importance of pregnandiol and estrogens in pregnancies in patients with
      previously pathological pregnancies].

PMID- 14954672
TI  - [Two cases of cystalgic pollakiuria with clear urine of hyperfolliculin origin;
      attempt at pathogenic interpretation].

PMID- 14954673
TI  - [Presentation of the biopsy curette of Dr. Philippe].

PMID- 14954674
TI  - [Treatment of cervicitis by submucosal infiltration of penicillin with
      streptomycin].

PMID- 14954675
TI  - [Right tubo-interstitial pregnancy 6 years after right salpingo-ovariectomy].

PMID- 14954676
TI  - [Multiple tumors of the ovary and uterus after intense cortisone therapy].

PMID- 14954677
TI  - [Histogenesis of ovarian tumors].

PMID- 14954678
TI  - [Modifications of Schorr's staining in the hormonal diagnosis of vaginal smears].

PMID- 14954679
TI  - [New prosthesis for the creation of an artificial vagina].

PMID- 14954680
TI  - [Report on the technic of the artificial vagina or vaginoplasty].

PMID- 14954681
TI  - [Eleven observations on congenital absence of the vagina].

PMID- 14954682
TI  - [Endometriosis].

PMID- 14954683
TI  - [Fundamental principles of the organization of obstetrical and gynecological aid
      in U.S.S.R..].

PMID- 14954684
TI  - [Subclinical tubal tuberculosis].

PMID- 14954685
TI  - [The need for coordination between physicians and hygienists].

PMID- 14954686
TI  - [Pulmonary caverns in the paramediastinal region in children].

PMID- 14954687
TI  - [Recent developments in urogenital tuberculosis].

PMID- 14954688
TI  - [Antihistaminic therapy of glomerulonephritis in children].

PMID- 14954689
TI  - [Heredity of syphilis].

PMID- 14954690
TI  - [Procaine amide therapy of extra-systolic ventricular arrhythmia].

PMID- 14954691
TI  - [International days light; 26-30 September 1951].

PMID- 14954693
TI  - [Social security].

PMID- 14954692
TI  - [The problem of retirement of physicians].

PMID- 14954694
TI  - [Adoption and legitimacy after adoption; medico-psychologic and legal aspects].

PMID- 14954695
TI  - [French medicine in China. I. French medicine at Shanghai].

PMID- 14954696
TI  - [Salt in diets of the Coniagui of Guinea].

PMID- 14954697
TI  - [Mechanism of conflicting opinion].

PMID- 14954698
TI  - [Biological basis of the pneumoconiosis].

PMID- 14954699
TI  - [Treponema immobilization test].

PMID- 14954700
TI  - [Oxycephaly].

PMID- 14954701
TI  - [Arsenic and rectal neoplasms].

PMID- 14954702
TI  - [Rheumatism; cortisone and aspirin].

PMID- 14954704
TI  - [Not Available].

PMID- 14954703
TI  - [Eczema and its therapy].

PMID- 14954705
TI  - [Session on rural medicine in Angers; 14-15 June 1952].

PMID- 14954706
TI  - [Social security. I. National Social Security plan].

PMID- 14954707
TI  - [Industrial hygiene].

PMID- 14954708
TI  - [French medicine in China. II. French medicine at Shanghai].

PMID- 14954709
TI  - [New aspects of renal physiology].

PMID- 14954710
TI  - [Clinical considerations on oxitocic therapy].

PMID- 14954711
TI  - [Extrapleural pneumothorax; indication and technic, advantages and disadvantages,
      experience and statistics].

PMID- 14954712
TI  - [Resistance, of Mycobacterium tuberculosis to isonicotinic acid hydrazide in the
      treatment of cavitary pulmonary tuberculosis].

PMID- 14954713
TI  - [Recurrent rhinitis in asthma].

PMID- 14954714
TI  - [The novelist Pio Baroja].

PMID- 14954715
TI  - [Federico Oloriz, exaltation of pedagogic sentiments].

PMID- 14954716
TI  - [Conversation among Mycobacterium tuberculosis, medico-literary fantasy].

PMID- 14954717
TI  - [Titration of barbital derivatives].

PMID- 14954718
TI  - [Sieve specifications in various pharmacopeias].

PMID- 14954719
TI  - [Chemical determination of digitalis glycosides].

PMID- 14954720
TI  - [Adrenalin and noradrenalin; a review].

PMID- 14954721
TI  - [Names approved by the Scandinavian pharmacopeial committee].

PMID- 14954722
TI  - [New results in histopathology of scleroderma adultorum (Buschke)].

PMID- 14954723
TI  - [Therapeutic and laboratory experiments with bismocillin; preliminary report].

PMID- 14954724
TI  - [Hamburg Dermatology Society].

PMID- 14954725
TI  - [Symptoms and blood vessel changes in ulcus cruris].

PMID- 14954726
TI  - [Investigations on ultravisible varieties of mycobacterium tuberculosis in lupus
      vulgaris].

PMID- 14954727
TI  - [Norwegian scabies in a patient with cutaneous reticulosis].

PMID- 14954728
TI  - [GERMAN Society for Occupational Safety c.V].

PMID- 14954729
TI  - [Hamburg Dermatology Society].

PMID- 14954730
TI  - [To Edmund Lesser on his 100th birthday].

PMID- 14954731
TI  - [A strange steatogenous basalioma].

PMID- 14954732
TI  - [Lichen amyloidosus resembling verrucous lichen chronicus Vidal].

PMID- 14954733
TI  - [Therapy of fresh keloids with hyaluronidase].

PMID- 14954734
TI  - [Frankfurt Dermatology Association].

PMID- 14954735
TI  - [Experiences with the arsenobenzene preparation Spirotrypan (Hoechst) in
      syphilis].

PMID- 14954736
TI  - [Skin thermometry and oscillometry in prognosis of leg ulcer].

PMID- 14954737
TI  - [Additional investigations in experimental chemotherapy of tuberculosis
      (neoteban)].

PMID- 14954738
TI  - [Therapy of tuberculosis with neoteben (isonicotinic acid hydrazide)].

PMID- 14954739
TI  - [Myalgias and their therapy].

PMID- 14954740
TI  - [Listeriosis in man].

PMID- 14954741
TI  - [Phlebography and venous pressure in varcosities of the lower extremity].

PMID- 14954743
TI  - [Dreams].

PMID- 14954742
TI  - [Laparoscopic cholecystography and cholangiography].

PMID- 14954744
TI  - [Listeriosis of man].

PMID- 14954745
TI  - [Medicine and homoeopathy].

PMID- 14954746
TI  - [Berlin Medical Society].

PMID- 14954747
TI  - [Tongue changes in internal medicine].

PMID- 14954748
TI  - [Clinical diagnosis of leukoencephalitis].

PMID- 14954749
TI  - [General resistance and chemotherapy].

PMID- 14954750
TI  - [Syphilitic children from healthy mothers].

PMID- 14954751
TI  - [Acute infections and vitamin B2 deficiency].

PMID- 14954752
TI  - [Neurological diagnosis of prolapse of the disc].

PMID- 14954753
TI  - [Biological trends in psychiatry].

PMID- 14954754
TI  - [Symptoms and pathogenesis of periarthritis coxae (gluteal type)].

PMID- 14954755
TI  - [Pharmacologically induced hypotension to avoid operative hemorrhage].

PMID- 14954756
TI  - [Therapy of anemias of newborn and children with ferric compounds].

PMID- 14954757
TI  - [Pathogenesis and therapy of enuresis nocturna].

PMID- 14954758
TI  - [Therapy of circulatory disorders with biological drugs].

PMID- 14954759
TI  - [Vitamin E lowering blood pressure in essential hypotension].

PMID- 14954760
TI  - [Three wheel cycle in development of human malaria plasmodia].

PMID- 14954761
TI  - [Urine test with tincture of iodine, a new pregnancy test].

PMID- 14954762
TI  - [The skin wheel in diagnosis of acute abdominal diseases].

PMID- 14954763
TI  - [Protein problems in surgery].

PMID- 14954764
TI  - [Effects of TBI (conteben) on local inflammation].

PMID- 14954765
TI  - [Knuechel reaction as an additional measure in diagnosis of quality of pulmonary
      tuberculosis].

PMID- 14954766
TI  - [Therapy of morbus Bechterew].

PMID- 14954768
TI  - [Micro complement fixation reaction in diagnosis of lues].

PMID- 14954767
TI  - [Intragluteal injection of heteroplastic pituitary preparations in therapy of
      generative and vegetative ovarial insufficiency].

PMID- 14954770
TI  - [Evaluation of diencephalic diseases].

PMID- 14954769
TI  - [Therapy of infantile eczema with cortisone].

PMID- 14954771
TI  - [Traumatic peripheral nerve damages in general practice].

PMID- 14954772
TI  - [Blood circulation in chronic brain injury].

PMID- 14954773
TI  - [Prognosis of pregnancy in prediabetic and diabetic women].

PMID- 14954774
TI  - [Severe allergic reactions caused by paraminosalicylic acid].

PMID- 14954775
TI  - [Problems of modern therapy of vaginal discharge].

PMID- 14954776
TI  - [Stellate ganglion block in bronchial asthma].

PMID- 14954777
TI  - [Attempts of prophylaxis of thromboembolism with hirudoid ointment].

PMID- 14954778
TI  - [Letter from Iran].

PMID- 14954779
TI  - [Chronic carbon monoxide poisoning].

PMID- 14954780
TI  - [Therapy of bronchopneumonia in children].

PMID- 14954781
TI  - [Clinical results of clearance methods].

PMID- 14954782
TI  - [Effects of paraaminohippuric acid on creatinine clearance].

PMID- 14954783
TI  - [Mitral stenosis and pregnancy].

PMID- 14954784
TI  - [State and neurosis; the problem of war neuroses].

PMID- 14954785
TI  - [The so-called syndrome Mauriac].

PMID- 14954786
TI  - [Problems of University education in England].

PMID- 14954787
TI  - [Berlin Medical Society].

PMID- 14954788
TI  - [Therapy of rheumatic diseases of the temporomandibular joint with adrenal
      cordical hormones].

PMID- 14954789
TI  - [Problematic and technic of replantation].

PMID- 14954790
TI  - [Aides for orthodontic plates].

PMID- 14954791
TI  - [Alveolar hemorrhage as first symptom of a case of acute myeloid leukemia].

PMID- 14954792
TI  - [Pavlov Conference in Dresden, February 9, 1952].

PMID- 14954793
TI  - [Tooth extraction in orthodontics].

PMID- 14954794
TI  - [Surgical therapy of prognathism].

PMID- 14954795
TI  - [New aids in functional dental orthopedics].

PMID- 14954796
TI  - [Dental orthopedics in social medicine].

PMID- 14954797
TI  - [Meeting of the German Work Group for Herd Research and Herd Control (registered
      society), Bad Nauheim, April 16-17, 1952].

PMID- 14954798
TI  - [To Carl Fritsch on his 70th birthday].

PMID- 14954799
TI  - [Elimination and use of pull and pressure in tissue transplantation for face
      plastic].

PMID- 14954800
TI  - [Impression and model technic in orthodontics].

PMID- 14954801
TI  - [Adhesion base from soft-staying material for full lower dental prosthesis].

PMID- 14954802
TI  - [Prophylaxis of the cuspid gap in adults caused by congenital absence of the
      upper lateral incisor].

PMID- 14954803
TI  - [Partial dental prosthesis in social practice].

PMID- 14954804
TI  - [Dental focal infection--from another view point].

PMID- 14954805
TI  - [New aspects of streptococci in mouth and saliva].

PMID- 14954806
TI  - [The significance of the oral clasp arm].

PMID- 14954807
TI  - [Analysis of a case of agnosia; case report].

PMID- 14954808
TI  - [Leptomeningeal branches of the trigeminal nerve].

PMID- 14954809
TI  - [A case of general absence of tendon reflexes; neurophysiological examination].

PMID- 14954810
TI  - [Histopathological observations of the sympathetic nervous system after x-ray
      therapy of a carcinoma of the larynx].

PMID- 14954811
TI  - [Symptoms and pathogenesis of myotonic dystrophy].

PMID- 14954812
TI  - [The problem of so-called accompanying movements after paralysis of the facial
      nerve].

PMID- 14954813
TI  - [Origin of proteins of cerebrospinal fluid].

PMID- 14954814
TI  - [Progressive postpoliomyelitic syndromes].

PMID- 14954815
TI  - [32 Years experiments in the years 1896-1928; a historical review].

PMID- 14954816
TI  - [Experimental ascites produced by osmotic effect of highly concentrated solutions
      of dextrose, polyvinylpyrroldon and dextran. Animal experiments on Buerger's
      osmotherapy].

PMID- 14954817
TI  - [Periotoneal osmotherapy with dextrose, kollidon and dextran in uremia;
      experiments on rabbits with salyrgan poisoning].

PMID- 14954818
TI  - [Tissue laundry in icterus by osmotic means].

PMID- 14954819
TI  - [Antibiotic therapy of leptospiroses].

PMID- 14954820
TI  - [Casual therapy of acute pancreatitis].

PMID- 14954821
TI  - [Effect of buscopan on action currents of the stomach].

PMID- 14954822
TI  - [Blood and tissue sugar in healthy and diabetic].

PMID- 14954823
TI  - [Comparative investigations on the effects of honey and invert sugar on the blood
      sugar].

PMID- 14954824
TI  - [Parenteral nutrition with fat infusions].

PMID- 14954826
TI  - [Differential diagnosis and therapy of certain types of jaundice].

PMID- 14954825
TI  - [Diseases causes by food].

PMID- 14954827
TI  - [Aspergillosis of infantile lungs].

PMID- 14954829
TI  - [Present knowledge of pathogenesis of skin malignancies].

PMID- 14954828
TI  - [Luvatren in shock therapy and in the therapy of extrapyramidal motion
      disorders].

PMID- 14954830
TI  - [Theory and practice of blood coagulation. III. Therapeutic use of heparine and
      dicumarol].

PMID- 14954831
TI  - [Diagnosis, differential diagnosis and symptoms of the manifestations of
      congenital syphilis on the ear].

PMID- 14954832
TI  - [Hygienic importance of ammonium hydrozide and additional ammonium compounds].

PMID- 14954833
TI  - [Local therapy of acne vulgaris].

PMID- 14954834
TI  - [Therapy of epidermophytiae with mycoderm].

PMID- 14954835
TI  - [Early diagnosis of icteric syndrome].

PMID- 14954836
TI  - [Analysis of ovarial function by checking basal temperatures; technical
      improvement of the method].

PMID- 14954837
TI  - [A new pregnancy test].

PMID- 14954838
TI  - [Medical care of civilian population in the Soviet Union].

PMID- 14954839
TI  - [2. Meeting of the German Association for Allergy Research, Frankfurt/Main, April
      19-20, 1952].

PMID- 14954840
TI  - [Short report from the 33.meeting of the German Radiology Society, Baden-Baden,
      September 26-29, 1951].

PMID- 14954841
TI  - [Second International Poliomyelitis Conference].

PMID- 14954842
TI  - [What is your diagnosis?].

PMID- 14954843
TI  - [Purulent acute meningitis in infants].

PMID- 14954844
TI  - [Traumatic chylothorax].

PMID- 14954845
TI  - [Primary melanoblastoma of the posterior fossa].

PMID- 14954846
TI  - [First experimental and clinical reports on isonicotinic acid hydrazide].

PMID- 14954847
TI  - [Municipal order modifying Carrera Medica Asistenical].

PMID- 14954848
TI  - [Myocardial infarct as industrial accident].

PMID- 14954849
TI  - [Periodic health examinations; history; fundamentals; objectives].

PMID- 14954850
TI  - [Echinococcosic pio pneumothorax].

PMID- 14954851
TI  - [Perforations of the sigmoid colon].

PMID- 14954852
TI  - [Epidemiological investigation of Chagas' disease in the western part of the
      province of Buenos Aires].

PMID- 14954853
TI  - [Auxiliary pedagogical treatment in cases of mental lassitude in normal
      children].

PMID- 14954854
TI  - [Intramedullary nailing in fractures of the femoral diaphysis].

PMID- 14954855
TI  - [Pathogenesis of hyperthyroidism].

PMID- 14954856
TI  - [Hormonal origin of arterial hypertension].

PMID- 14954857
TI  - [Anesthesia in surgical treatment of heart disease].

PMID- 14954858
TI  - [Intra-arterial insulin therapy in diabetic arteriosclerosis of the leg with
      intermittent claudication].

PMID- 14954859
TI  - [Surgery for pain in inoperable malignant proctologic processes].

PMID- 14954860
TI  - [Acute abdomen in pediatrics; general physiopathology].

PMID- 14954861
TI  - [Focal infection and alarm reaction in connection with collagenosis and
      neuroclinical diseases].

PMID- 14954862
TI  - [Inefficacy of cortisone therapy].

PMID- 14954863
TI  - [Use of progesterone for differential diagnosis of pregnancy and first degree
      amenorrhea].

PMID- 14954864
TI  - [Skin allergy].

PMID- 14954865
TI  - [Parathyroid function; primary and secondary hyperparathyroidism].

PMID- 14954866
TI  - [Drug allergy].

PMID- 14954867
TI  - [Xanthomatosis secondary to chronic choledochus syndrome].

PMID- 14954868
TI  - [The Cherney incision].

PMID- 14954869
TI  - [Schickele syndrome" of Peralta Ramos and "medical delivery" of Kreis].

PMID- 14954870
TI  - [Abdominal contusions].

PMID- 14954871
TI  - [Therapy of thyrotoxicosis with radioactive iodine].

PMID- 14954872
TI  - [Surgery in congenital abnormalities of the circulatory system].

PMID- 14954873
TI  - [Drug therapy of amenorrhea].

PMID- 14954874
TI  - [Orthoptic therapy of strabismus].

PMID- 14954875
TI  - [Hepatolenticular degeneration (two cases in one family].

PMID- 14954876
TI  - [Treatment of alcohol with antabuse].

PMID- 14954877
TI  - [The distant future of meningeal tuberculosis cured by streptomycin].

PMID- 14954878
TI  - [Precategorical thought in children].

PMID- 14954879
TI  - [Perception of space, speed and time in the five year-old child; critical study
      of the works of Jean Piaget II. Time].

PMID- 14954880
TI  - [The role of language in mental development; contribution of deaf-mute child
      psychology].

PMID- 14954881
TI  - [Architecture and the child].

PMID- 14954882
TI  - [Variations of personality levels in the child explained by tests].

PMID- 14954883
TI  - [The American Negro child and race discrimination].

PMID- 14954884
TI  - [Educational films in the modern school and life].

PMID- 14954885
TI  - [Classes in vocational education in Lyons].

PMID- 14954886
TI  - Experimental jaundice.

PMID- 14954887
TI  - Effect of individual vitamins A, C, E, and carotene administered at high levels
      on their concentration in the blood.

PMID- 14954888
TI  - Effect of dietary carbohydrate on the growth-promoting properties of fat in the
      hyperthyroid rat.

PMID- 14954889
TI  - The inhibitory and necrosis-inducing effects of the latex of Ficus carica L. on
      transplanted and spontaneous tumours.

PMID- 14954890
TI  - Effect of urine extracts from cancer patients on rat gonads and spleen; a reply
      to Wilt and Nicholson.

PMID- 14954891
TI  - Pathological findings in fluorine intoxication.

PMID- 14954892
TI  - Further study of the role played by fluorine in the causation of disease.

PMID- 14954893
TI  - The danger of digitalis preparations, especially strophanthin.

PMID- 14954894
TI  - Degenerative joint disease in mice fed a high-fat diet at various ages.

PMID- 14954895
TI  - A comparative study of effects of coumarines by the use of a microprothrombin
      method.

PMID- 14954897
TI  - Tumors; dry clinic.

PMID- 14954896
TI  - The collagen diseases; differential diagnosis with special reference to the eye,
      ear, nose and throat.

PMID- 14954898
TI  - Eponymic syndromes of the skin, eyes, ears, nose and throat.

PMID- 14954899
TI  - Dermatitis from cosmetics with special reference to the ocular and facial areas.

PMID- 14954900
TI  - Oral manifestations of the blood diseases.

PMID- 14954901
TI  - Superficial mycotic infections of the eyes, ears, nose and oral cavity.

PMID- 14954902
TI  - "SORE mouth"-diseases of the oral mucous membranes.

PMID- 14954903
TI  - Tracheotomy and poliomyelitis.

PMID- 14954904
TI  - Tonography as a routine procedure.

PMID- 14954905
TI  - [Experimental study of the therapeutic value of chloramphenicol administered
      parenterally].

PMID- 14954906
TI  - [Synthesis of tetrahydrothiopyran-4'5-spirobarbituric acid].

PMID- 14954907
TI  - [Bile acids and their derivatives. Note V. A new method of degradation to nor
      acids].

PMID- 14954908
TI  - [Antibacterial activity of derivatives of quinoline. VI. Preparation of some
      Schiff bases from quinoline-8-aldehyde].

PMID- 14954909
TI  - [Determination and recognition of hormonal steroids contained in pharmaceutic
      preparations. I. Method for control of oily solution of testosterone propionate].

PMID- 14954910
TI  - [Some new derivatives of thiosemicarbazide. III..].

PMID- 14954911
TI  - [Action of some oxyaromatic acids on the elimination of 17-ketosteroids and on
      the eosinophil count].

PMID- 14954912
TI  - [Contribution to the knowledge of cafestol (cafesterol). I].

PMID- 14954913
TI  - [Chemical, physicochemical and biological problems which may be solved with the
      use of radioactive isotopes and chemical effects of neutron bombardment of
      organic nitrogenous substances].

PMID- 14954914
TI  - [The B12 group and the new directions of the U.S. Pharmacopeia].

PMID- 14954915
TI  - [Official microbiological method of the U.S.P. XIV for the evaluation of the
      activity of vitamin B12].

PMID- 14954916
TI  - [Hyaluronidase and its therapeutic applications].

PMID- 14954917
TI  - [New class of synthetic analeptics].

PMID- 14954918
TI  - [New curare simulants].

PMID- 14954919
TI  - [Chemotherapeutic thiosemicarbazones with extensive antibacterial activity].

PMID- 14954920
TI  - [Studies on substances with presumable antituberculous chemotherapeutic action.
      I. Hydroxyl acylated PAS derivatives].

PMID- 14954921
TI  - [Studies on substances with presumable antituberculous chemotherapeutic action.
      II. Thiosemicarbazones of p-aminosalicylic aldehyde and some of its derivatives].

PMID- 14954922
TI  - [Studies on substances with presumable antituberculous chemotherapeutic action.
      III. 6-aminosalicylic acid].

PMID- 14954923
TI  - [Studies on sub stances with presumable antituberculous chemo therapeutic action.
      IV. Salicylic acid derivatives with different nitrated substitutes in the para
      position].

PMID- 14954924
TI  - [Advantage of bioassay of strophanthin preparations and stabilization of standard
      unit].

PMID- 14954925
TI  - [Extraction of l-noradrenalin from the adrenal gland and its pharmacobiological
      action].

PMID- 14954926
TI  - [Applications of electrometric methods to the determination of pharmaceutical
      products. V. Conductometric and potentiometric determination of barbiturates].

PMID- 14954927
TI  - [New Italian industry; production of caffeine directly from raw coffee].

PMID- 14954928
TI  - [Vitamin complex with antianemic action in liver extracts].

PMID- 14954929
TI  - [Comparative study of the antibacterial activity of quinoline derivatives and
      aromatic amines].

PMID- 14954930
TI  - [New method for the degradation of bile acids].

PMID- 14954931
TI  - [Action of insulin associated with hyaluronidase].

PMID- 14954932
TI  - [Mechanism of corrosion of glass by aqueous solutions].

PMID- 14954933
TI  - [Some directions for obtaining immune sera with application to the human
      species].

PMID- 14954934
TI  - [Chemistry of antibiotics].

PMID- 14954935
TI  - [Organization and operation of a laboratory for radioisotope research].

PMID- 14954936
TI  - [Standardization of drug toxicity tests].

PMID- 14954937
TI  - [Standardization of apparatus for the chemical pharmaceutical industry].

PMID- 14954938
TI  - [Calculation of industrial costs in the pharmaceutical industry].

PMID- 14954939
TI  - [Patents in the chemical pharmaceutical industry].

PMID- 14954940
TI  - [Medicinal drugs in the work of Fernando de Sepulveda. III].

PMID- 14954941
TI  - [Couerbe's meconin, staphisin and sabadillin].

PMID- 14954942
TI  - [Pharmacognostic examination of powders from cardiotonic drugs from plants].

PMID- 14954943
TI  - [Effect of the quantity of glucoside injected and its toxicity for cats,
      according to the method of Hatcher-Magnus].

PMID- 14954944
TI  - [Contribution to the introduction of the oxidation factor of essences as an
      analytic constant].

PMID- 14954946
TI  - [Answer of the physiologist to psychologists].

PMID- 14954945
TI  - [Note on the hydrastine content in cultivated Hydrastis canadensis L].

PMID- 14954947
TI  - [Etiology and clinical aspects of trachoma].

PMID- 14954948
TI  - [Penicillin therapy of acute conjunctivitis in polyclinics].

PMID- 14954949
TI  - [Vaccination against dysentery].

PMID- 14954950
TI  - [Intoxications with hydrogen sulfide and their prevention].

PMID- 14954951
TI  - [Decabrist-physician F. B. Vol'f].

PMID- 14954952
TI  - [Delivery in pelvic presentation].

PMID- 14954953
TI  - [Surgical scrub].

PMID- 14954954
TI  - [Painless injections].

PMID- 14954955
TI  - [Diagnosis of flatfoot].

PMID- 14954956
TI  - [Role of feldsher in construction of the Main Turkmensk Canal].

PMID- 14954957
TI  - [Hepatic parasites in men].

PMID- 14954958
TI  - [Medical services for workers in clothing factories].

PMID- 14954959
TI  - [Hemorrhoids and their therapy].

PMID- 14954960
TI  - [Work of the assistant to the physician epidemiologist in a city epidemiological
      station].

PMID- 14954961
TI  - [Diuretics of vegetable origin].

PMID- 14954962
TI  - [Diets for subtotal gastrectomized patients].

PMID- 14954963
TI  - [Cytological diagnosis by phase contrast microscopy].

PMID- 14954964
TI  - [Child welfare].

PMID- 14954965
TI  - [Ectrodactylia].

PMID- 14954966
TI  - [Treatment of asthma with antihistamine aerosols].

PMID- 14954967
TI  - [Anti-pruriginous effect of antihistamines in chickenpox].

PMID- 14954968
TI  - [Counselor Cruz Jobim].

PMID- 14954969
TI  - [Iso-immunization and infertility].

PMID- 14954970
TI  - [Orthopedic surgery; modern progress].

PMID- 14954971
TI  - [Modern concepts in the treatment of diabetes].

PMID- 14954972
TI  - [A new basic line to study sagittaltele radiograms with great exactness].

PMID- 14954974
TI  - [Experience with the lingual activator].

PMID- 14954973
TI  - [Elasticity of the bony structure of the juvenile dental system].

PMID- 14954975
TI  - [Orthopedic therapy of the cheilo-gnatopalatoschisis].

PMID- 14954976
TI  - [Enlargement and diminution of the chin].

PMID- 14954977
TI  - [Etiology and genesis of abnormalities of the dentition].

PMID- 14954978
TI  - [The technic of gastric intubation and the interpretation of the results].

PMID- 14954979
TI  - [The use of agents affecting gastrointestinal function in radiography].

PMID- 14954980
TI  - [Hemorrhoid sclerosing injections, indications, technic and incidence].

PMID- 14954981
TI  - [Liver function tests].

PMID- 14954982
TI  - [Hemorrhagic recto-colitis].

PMID- 14954983
TI  - [Chronometric duodenal intubation for the study of biliary dyskinesia].

PMID- 14954984
TI  - [Deviation of the esophagus in mitral insufficiency].

PMID- 14954985
TI  - [Chronic cor pulmonale in silicosis].

PMID- 14954986
TI  - [Blood pressures in the heart cavities and in the blood vessels measured during
      heart catheterization].

PMID- 14954987
TI  - [Potassium metabolism and the electrocardiogram].

PMID- 14954988
TI  - [Diagnostic value of criteria of ventricular hypertrophy in right heart block].

PMID- 14954989
TI  - [Scleroderma and cardiac insufficiency].

PMID- 14954990
TI  - [Myxedema and myxedematous heart].

PMID- 14954991
TI  - [Information provided by radioscopic examination of the heart and aorta in
      general practice].

PMID- 14954992
TI  - [Therapy of rheumatic heart disease with cortisone and ACTH].

PMID- 14954993
TI  - [Diagnosis of bradycardia].

PMID- 14954994
TI  - Treatment of ulcerative colitis.

PMID- 14954995
TI  - Poison liquor.

PMID- 14954996
TI  - Treatment of hay fever in children.

PMID- 14954997
TI  - Modern concepts of shock and its treatment.

PMID- 14954998
TI  - Diagnosis and treatment of the anemias.

PMID- 14955000
TI  - The golden rule in politics.

PMID- 14954999
TI  - Headaches: their analysis and treatment.

PMID- 14955001
TI  - Watch out...accident about to happen.

PMID- 14955002
TI  - Retirement income at 65 policies.

PMID- 14955003
TI  - Presidential address presented by J. P. Sanders, M.D., to the Congress of
      Delegates at the Fourth Annual Scientific Assembly at Atlantic City, New Jersey,
      1952.

PMID- 14955004
TI  - UNDERGRADUATE education for general practice: a report by Commission on
      Education.

PMID- 14955005
TI  - On the chromosomes of Yoshida sarcoma; studies with tumor cells proliferated in
      the peritoneal cavity of the rat transplanted with a single cell.

PMID- 14955006
TI  - Cytological studies on cancer. III. The characteristics and individuality of
      chromosomes in tumor cells of the Yoshida sarcoma which contribute to the growth
      of the tumor.

PMID- 14955007
TI  - Cytological studies on cancer. V. Heteroplastic transplantations of the Yoshida
      sarcoma, with special regard to the behaviour of tumor cells.

PMID- 14955008
TI  - A case of double malignant tumors, carcinoma of the prostate and the urinary
      bladder in a single patient.

PMID- 14955009
TI  - Investigations on the nature of K. I. K. factor in gastric juice from gastric
      cancer patients.

PMID- 14955010
TI  - Toxohormone and thymus involution in tumor-bearing animals; a fourth study on
      toxohormone, a characteristic toxic substance produced by cancer tissue.

PMID- 14955011
TI  - [On hypertrophic, so-called pseudotumerous gastritis].

PMID- 14955012
TI  - [Experimental production of gastric ulcer in rats and the therapeutic effect of
      robuden].

PMID- 14955013
TI  - [Neurochemical reflexes and gastric motility].

PMID- 14955014
TI  - [Clinical and bacteriological examination of a new intestinal therapeutic agent
      in the treatment of various forms of colitis].

PMID- 14955015
TI  - [Interruption of the nasal reflexes in the treatment of gastroduodenal ulcer,
      with theoretical observations on etiology and therapy].

PMID- 14955016
TI  - The president's address: comments on the membership of the American
      Gastroenterological Association.

PMID- 14955017
TI  - Congenital dysplasia of the interlobular bile ducts with extensive skin
      xanthomata; congenital acholangic biliary cirrhosis.

PMID- 14955018
TI  - The implications of failure of the gastroscope to pass the cardiac orifice of the
      stomach.

PMID- 14955019
TI  - Repeated blood volume determinations in bleeding peptic ulcer.

PMID- 14955020
TI  - Amebiasis: some features of the disease revealed by the study of autopsy material
      from 96 cases.

PMID- 14955021
TI  - Experience with a new cholecystographic medium (telepaque).

PMID- 14955022
TI  - The guaiac test-correlation with clinical findings.

PMID- 14955023
TI  - A new instrument for gastric biopsies under visual control.

PMID- 14955024
TI  - Gastric acid response to massive doses of insulin: I. Prolonged observations on
      one individual.

PMID- 14955025
TI  - The Shay rat as an assay animal for anti-ulcer factors: III. Paper chromatography
      and other chemical studies of Shay rat anti-ulcer factors.

PMID- 14955026
TI  - The Shay rat as an assay animal for anti-ulcer factors: IV. The effect of
      adrenalectomy and nephrectomy.

PMID- 14955027
TI  - A comparative study of the effect of oral and subcutaneous banthine on gastric
      secretion from a new innervated gastric pouch.

PMID- 14955028
TI  - The effect of lysozyme on canine gastrointestinal mucosa; further study.

PMID- 14955029
TI  - The effect of bentyl hydrochloride on the choledocho-duodenal region in dogs.

PMID- 14955030
TI  - Intussusception in the aged: ileal-ileal type with spontaneous auto-amputation
      and expulsion of the necrotic segment.

PMID- 14955031
TI  - Duodenal ulcer producing obstructive jaundice.

PMID- 14955032
TI  - Carcinoma of the body and tail of the pancreas.

PMID- 14955033
TI  - The vagotomy problem.

PMID- 14955034
TI  - [Great figures of Portuguese medicine].

PMID- 14955035
TI  - [Pemphigus erythematosus (Senear-Usher syndrome)].

PMID- 14955036
TI  - [Crouzon's syndrome].

PMID- 14955037
TI  - [Duodenal diverticula; clinical manifestations and radiological diagnosis].

PMID- 14955038
TI  - The management of rheumatoid arthritis; current concepts; a review.

PMID- 14955039
TI  - [Case of primary vaginal carcinoma and its probable etiology].

PMID- 14955040
TI  - [Maxillo-facial centers].

PMID- 14955041
TI  - [Physiopathology of the testes].

PMID- 14955042
TI  - [Iatrogenic heart disease].

PMID- 14955043
TI  - [Presentation of a sphygmoplethysmograph for the study of peripheral
      circulation].

PMID- 14955044
TI  - [Coarctation of the aorta (adult type) with probable dissecting aneurysm].

PMID- 14955045
TI  - [Notes on the normal hemogram].

PMID- 14955046
TI  - [Green pigment of the chloroma].

PMID- 14955047
TI  - [A new liver function test: the Wuhrmann-Wunderly cadmium reaction; comparison
      with Hanger reaction].

PMID- 14955048
TI  - [Decubitus ulcers].

PMID- 14955049
TI  - [New aspects of the cancer problem in gynecology].

PMID- 14955050
TI  - [Exchange transfusion in erythroblastosis fetalis; indication and technique].

PMID- 14955051
TI  - [Changes in the gynecological diseases in the last 50 years].

PMID- 14955052
TI  - [Transversal extraperitoneal cesarean section].

PMID- 14955053
TI  - [Vaginal smear in the differential diagnosis of benign gynecological diseases].

PMID- 14955054
TI  - [Depot strychnine in induction of labor].

PMID- 14955055
TI  - [Frequency of malformations at the gynecological University Hospital Greifswald
      from 1930 to 1950].

PMID- 14955056
TI  - [Familial hydrocephalus].

PMID- 14955057
TI  - [A rare malformation of the uterus; uterus unicorporeus, cervix transversum
      septa, biloris].

PMID- 14955058
TI  - [Torsion of an ovarial cystoma in puerperium, resembling ileus].

PMID- 14955059
TI  - [Connection between Rh incompatibility of the parents and habitual abortion].

PMID- 14955060
TI  - [Spontaneous delivery after reposition of a pelvic kidney].

PMID- 14955061
TI  - [Not Available].

PMID- 14955062
TI  - [Prevention of pregnancy complications].

PMID- 14955063
TI  - [A question of systemic disease].

PMID- 14955064
TI  - [Proposed law on burials; medical secrecy].

PMID- 14955065
TI  - [Prevention of pregnancy complications].

PMID- 14955066
TI  - [Thyroid and pregnancy].

PMID- 14955067
TI  - [The development of industrial medicine in Netherlands].

PMID- 14955068
TI  - [Gerard van Swieten and Maria Theresa].

PMID- 14955069
TI  - [The value of 3-methyl 5.5. phenylethylhydantoin in therapy of epilepsy].

PMID- 14955070
TI  - [Problems of artificial insemination].

PMID- 14955072
TI  - [Debate on social and public health matters in the first chamber].

PMID- 14955071
TI  - [In memoriam Prof. Dr. J. van der Hoeve (1878-1952)].

PMID- 14955073
TI  - [Notes on tuberculosis therapy with reference to the 1950 report of the Stichting
      Ned. Sanatorium-Verzekering and its medical consultant].

PMID- 14955074
TI  - [Venous thrombosis and pulmonary embolism (acute cor pulmonale)].

PMID- 14955075
TI  - [Chronic cor pulmonale].

PMID- 14955076
TI  - [Hypertension].

PMID- 14955077
TI  - [Psychosomatic factors in heart disease].

PMID- 14955078
TI  - [The reactions of the English to the National Health Service Act].

PMID- 14955079
TI  - [Peripheral arterial circulatory disorders from the internal medical point of
      view].

PMID- 14955080
TI  - [Surgery in peripheral arterial diseases].

PMID- 14955081
TI  - [Varices and hemorrhoids].

PMID- 14955082
TI  - [Study on pathological changes in artery implantation in dogs].

PMID- 14955083
TI  - [Proposed law on protection of school children against infection].

PMID- 14955084
TI  - [Law on requirements for diploma in nursing].

PMID- 14955085
TI  - A statistical study of the Freudian theory of levels of psychosexual development.

PMID- 14955086
TI  - Personality characteristics of selected disability groups.

PMID- 14955087
TI  - [Wertheim's operation].

PMID- 14955088
TI  - [Longitudinal esthetic low micro-incision in cesarean section].

PMID- 14955089
TI  - [15 Years of cesarean section at the General Hospital].

PMID- 14955090
TI  - [Cervical biopsy; review of 200 cases].

PMID- 14955091
TI  - [Deontological and ethical problems in gynecology].

PMID- 14955092
TI  - [Abdominal pregnancy at term with live infant].

PMID- 14955093
TI  - [Attempted therapy of cancer of the cervix uteri with progesterone; clinical,
      cytological, and histological study and results].

PMID- 14955094
TI  - [Use of lipiodol-ether mixture in hysterosalpingography; clinical, experimental,
      and bacteriologic studies].

PMID- 14955095
TI  - [Studies on action of estrogen in woman; use of ethinyl estradiol and bisdehydro
      isynolic acid].

PMID- 14955096
TI  - [Use and administration of hormones in threatened abortion].

PMID- 14955097
TI  - [Present knowledge of cancer in situ of the cervix uterine].

PMID- 14955098
TI  - [Considerations on therapeutic abortion].

PMID- 14955099
TI  - [Supression of so-called therapeutic abortion].

PMID- 14955100
TI  - [Pelvic pain in gynecology; etiology and pathogenesis].

PMID- 14955101
TI  - [Female genital flux].

PMID- 14955102
TI  - [Project for a classification and a nomenclature of menstrual disorders].

PMID- 14955103
TI  - [Classification and nomenclature of menstrual disorders].

PMID- 14955104
TI  - [Use and administration of sex hormones in menstrual cyclic abnormalities].

PMID- 14955105
TI  - [Clinical and radiographic studies on the cephalo-pelvic relation in primigravida
      at term].

PMID- 14955106
TI  - [Treatment of anemia with ferric-arsenical waters; behavior of peripheral and
      medullary blood picture].

PMID- 14955107
TI  - [Liver cirrhosis. Note I. Anemia syndromes of Laennec's cirrhosis in the ascitic
      stage].

PMID- 14955108
TI  - [Additional data on a titrimetric method of determination of lipidic fractions;
      age correlations in normal subjects].

PMID- 14955109
TI  - [Discoloration capacity of potassium permanganate combined with pathological
      serum and its use in diagnosis].

PMID- 14955110
TI  - [Cito-karyological study of chloro-amino action in some experimental lymphatic
      diseases].

PMID- 14955111
TI  - [Electrocardiographic changes in the Dagnini Aschner reflex].

PMID- 14955112
TI  - [Retroperitoneal tumors].

PMID- 14955113
TI  - [Penta- and hexamethonium in arterial hypertension].

PMID- 14955114
TI  - [First impressions of use of isonicotinic acid hydrazide in pulmonary
      tuberculosis bedridden subjects in the Rasori Sanatorium].

PMID- 14955115
TI  - [A practical modality in thoracic stratigraphy].

PMID- 14955116
TI  - [Hyperprotein and lipotropic therapy in liver cirrhosis; clinical study of 46
      cases hospitalized and followed-up in last five years].

PMID- 14955118
TI  - [Current concepts of the surgical treatment of mitral stenosis].

PMID- 14955117
TI  - [Anatomo-surgical study of relations between kidney and colon in formation of
      renal colonic fistulas].

PMID- 14955119
TI  - [Recovery from tubercular meningitis].

PMID- 14955120
TI  - [World medical congress for the study of current living conditions].

PMID- 14955121
TI  - [Essential amino acids].

PMID- 14955122
TI  - [Effect of certain drugs and preoperative manometric examination of extrahepatic
      bile ducts under anesthesia].

PMID- 14955123
TI  - [Experimental results with the apparatus for intra-arterial transfusions].

PMID- 14955124
TI  - [Oscillometric manifestations in diseases of the joints; oscillometry in
      articular tuberculosis].

PMID- 14955125
TI  - [Clinical studies on the effect of a new hemostatic].

PMID- 14955126
TI  - [Intrahepato-duodenostomy; report of a case].

PMID- 14955127
TI  - [Intravenous infusion of recorcaine in surgery].

PMID- 14955128
TI  - [Surgical instrument holder].

PMID- 14955129
TI  - [Methods of pulmonary resections and its indications in tuberculosis].

PMID- 14955130
TI  - [Preliminary data on pharmacology of isonicotinic acid hydrazide].

PMID- 14955131
TI  - [Statistical data on the relation of gastroduodenal ulcer to pulmonary
      tuberculosis].

PMID- 14955132
TI  - [Indications for extraperiosteal plombage with polyethylene in pulmonary
      tuberculosis].

PMID- 14955133
TI  - [Surgery in the surgical department of the sanatorium Citta di Milano].

PMID- 14955134
TI  - [Abnormal porphynuria in the treatment of pulmonary tuberculosis with
      thiosemicarbazones].

PMID- 14955135
TI  - [Glutathionemia consecutive to thoracoplasty for tuberculosis in a mountain
      sanatorium].

PMID- 14955136
TI  - [Studies on cardio-pulmonary function following thoracic surgery].

PMID- 14955137
TI  - [Studies on variation of the mode of reactivity of the organism in tuberculosis
      in relation to streptomycin and PAS therapy].

PMID- 14955138
TI  - [Unusual giant pulmonary cyst].

PMID- 14955139
TI  - [Relation of streptomycin and PAS to isonicotinic hydrazide].

PMID- 14955140
TI  - [Isonicotinic acid hydrazide at the Garbagnate Sanatorium].

PMID- 14955141
TI  - [Sedimentation rate and hemocytometric changes during isonicotinic acid hydrazide
      therapy].

PMID- 14955142
TI  - [Behavior of tuberculin allergy during isonicolinic acid hydrazide therapy].

PMID- 14955143
TI  - [Behavior of basal metabolism in nicotinic acid hydrazide therapy of pulmonary
      tuberculosis].

PMID- 14955144
TI  - [Clinical and anatomo-pathological findings in a case of miliary tuberculosis
      treated with isonicotinic acid hydrazide].

PMID- 14955145
TI  - [Liver function in isonicotinic acid hydrazide therapy of tuberculosis].

PMID- 14955146
TI  - [First controls on the anti-tuberculosis activity of isonicotinic acid
      hydrazide].

PMID- 14955147
TI  - [Chronic tuberculous empyema with multiple fistulae treated with isonicotinic
      acid hydrazide].

PMID- 14955148
TI  - [Radiological changes observed in 100 cases of pulmonary tuberculosis after 3
      months treatment with isonicotinic acid hydrazide].

PMID- 14955149
TI  - [Case of atypical fistulous empyema].

PMID- 14955150
TI  - [Course on tuberculosis at Leysin and organization of the anti-tuberculosis
      campaign in the Canton of Vaud, Switzerland].

PMID- 14955151
TI  - [First observations on the use of isonicotinic acid hydrazide in pulmonary
      tuberculosis in the adult; preliminary note].

PMID- 14955152
TI  - [Case studies on lung abscess].

PMID- 14955153
TI  - [Occupational therapy: industrial rehabilitation and spontaneous occupational
      therapy].

PMID- 14955154
TI  - [2 Unusual cases of pulmonary embolism caused by metal].

PMID- 14955155
TI  - [Variations in segmental circulation rate and venous pressure in alterations of
      muscle tone].

PMID- 14955156
TI  - [Low intensity electroshock therapy in psychiatry].

PMID- 14955157
TI  - [An unusual spino-cerebellar heredo-degenerative sequence].

PMID- 14955158
TI  - [Several less frequent applications of cerebral arteriography].

PMID- 14955159
TI  - [Confession].

PMID- 14955160
TI  - Perforated peptic ulcer: a study of 200 consecutive cases.

PMID- 14955161
TI  - Anticoagulants and anticoagulant therapy; a review.

PMID- 14955162
TI  - Fatal rheumatic pericarditis treated with cortisone. and ACTH.

PMID- 14955163
TI  - INFECTIOUS diseases and epidemiological notes; vital statistics for 5 weeks
      ending 31st May, 1952.

PMID- 14955164
TI  - Some problems of malaria from the standpoint of the general biologist.

PMID- 14955166
TI  - The Guy's hospital reports; a clinical lecture delivered on March 10th, 1952.

PMID- 14955165
TI  - Hypnotism and hysteria.

PMID- 14955167
TI  - Just pain.

PMID- 14955168
TI  - [1000 plastic operations; experiences and results].

PMID- 14955169
TI  - [Therapy of vaginal infections with antibiotics; II. Terramycin-amphoter].

PMID- 14955170
TI  - [Incidence of hidden iron deficiency in women, especially in pregnancy and
      puerperium].

PMID- 14955171
TI  - [Intrainguinal varicosities of the round ligament].

PMID- 14955172
TI  - [Serological structure of fetus to be aborted].

PMID- 14955173
TI  - [Effects of sex hormones and anterior pituitary hormone on the prothrombin level
      of the mature woman].

PMID- 14955174
TI  - [Masculinizing ovarial tumors].

PMID- 14955175
TI  - [Prevention of adhesions after laparotomy].

PMID- 14955176
TI  - The manifestation of biological rhythms in delivery.

PMID- 14955177
TI  - HIGHLIGHTS-1952 meeting American College of Physicians.

PMID- 14955178
TI  - Management of diabetes mellitus and its complications.

PMID- 14955179
TI  - Acute massive venous occlusion.

PMID- 14955180
TI  - Feeding normal children.

PMID- 14955181
TI  - Anesthesia problems in traumatic surgery.

PMID- 14955182
TI  - Cortisone to maintain patency of a lamina terminalis puncture in obstructive
      hydrocephalus.

PMID- 14955183
TI  - [Pathology of chronic stenosing diverticulitis coli (so-called diverticulitis
      tumor)].

PMID- 14955184
TI  - [Cerclage by folding and folding tighter. The problem of fracture surgery;
      special consideration of mechanical and biological viewpoints of fracture healing
      and of stabile osteosynthesis of long bones].

PMID- 14955185
TI  - [Studies on vascularization of neoplasms].

PMID- 14955186
TI  - [Tendon suture].

PMID- 14955187
TI  - [Osmotic blood pressure in relation to serum proteins].

PMID- 14955188
TI  - [Experimental investigations on adrenal in hypertension and associated
      cardiovascular and adrenal changes in the rat].

PMID- 14955189
TI  - [Chronic benzene poisoning].

PMID- 14955190
TI  - [Radiologic and clinical analogies between the pulmonary manifestations of Q
      fever and tuberculosis].

PMID- 14955191
TI  - [Pathology of the septum pellucidum in the pneumoencephalogram].

PMID- 14955192
TI  - [Cavum septi pellucidi; operative confirmation of diagnosis].

PMID- 14955193
TI  - [Acrocephalosyndactylia; pathogenesis seen from viewpoint of embryopathy].

PMID- 14955194
TI  - [Congenital scoliosis].

PMID- 14955195
TI  - [Eosinophilia and vegetative dysregulation associated with postencephalitic
      epilepsy].

PMID- 14955196
TI  - [Neurological symptoms of reversible megaloblastic anemia in infants].

PMID- 14955197
TI  - [A case of hypoplastic anemia with multiple congenital malformations (Fanconi's
      anemia0].

PMID- 14955198
TI  - Constitutional infantile panmyelopathy with multiple malformations Fanconi
      anemia.

PMID- 14955199
TI  - [Certain considerations on diagnosis of anemias].

PMID- 14955200
TI  - [General causes of female sterility].

PMID- 14955201
TI  - [Granulogram].

PMID- 14955202
TI  - [Certain considerations on staining streptomycin resistant and sensitive
      Mycobacterium tuberculosis].

PMID- 14955203
TI  - [Eosinophilia in bronchial asthma].

PMID- 14955204
TI  - [Case of intraocular neuritis due to pellagra].

PMID- 14955205
TI  - [Cortisone and ACTH in rheumatology practice].

PMID- 14955206
TI  - [Infiltration of the internal pudendal nerves during the expulsion period; 52
      observations].

PMID- 14955207
TI  - [Transitory recurrent essential arterial hypertension, mode of onset of arterial
      hypertension].

PMID- 14955208
TI  - [Hepatic cirrhosis and occupational diseases].

PMID- 14955209
TI  - [Hemorrhagic recto-colitis].

PMID- 14955210
TI  - [Partial nephrectomy].

PMID- 14955211
TI  - [Periodic infantile acetonemia].

PMID- 14955212
TI  - [Viscosimetric determination of hyaluronidase].

PMID- 14955213
TI  - [Paperchromatographic analysis of porphyrines].

PMID- 14955214
TI  - [Nucleoprotamine. II].

PMID- 14955215
TI  - [A few compounds related to adrenal cortical hormones].

PMID- 14955216
TI  - [Mechanism of thrombin formation in the isolated system].

PMID- 14955217
TI  - [Inhibition of coagulation by sulfuric acid esters of hyaluronic acid].

PMID- 14955218
TI  - [Correlations between heparin and the thrombin inactivation reaction of
      Gerendas].

PMID- 14955219
TI  - [Extraction of different kinds of leucocytes of the blood. I. Basophilic
      leucocytes].

PMID- 14955220
TI  - [Determination of chlorides in serum by electrometric differential titration].

PMID- 14955221
TI  - [Paperelectrophoretic differentiation of end products of nucleic acids. III].

PMID- 14955222
TI  - [Lipoids from the cyst membrane of Taenia echinococcus].

PMID- 14955223
TI  - [N(12)-formyl-folic acid, a fermentative metabolic product of folic acid].

PMID- 14955224
TI  - [Proteins and their metabolic products. VIII. Presence of norvaline and
      norleucine in proteins].

PMID- 14955225
TI  - [Elimination of interfering chromogens in determination of 17-ketosteroids with m
      dinitrobenzene].

PMID- 14955226
TI  - [A new method for quantitative determination of adrenal cortical hormones].

PMID- 14955227
TI  - [Distribution of aluminum in the blood of the horse, cattle and pig].

PMID- 14955228
TI  - [Interrelations between hemosiderin ferritin].

PMID- 14955229
TI  - [Comparison of inhibitory effects of 4'-alkoxi-stilbamines and their optic
      antipodes on cell division].

PMID- 14955230
TI  - [Comparison of inhibitory effects of colchicine, isocolchicine and homologous
      compounds on cell division].

PMID- 14955231
TI  - [Nucleoprotamine. III].

PMID- 14955232
TI  - [Acetylcholine in mammalian blood].

PMID- 14955233
TI  - [Quantitative determination of pregnandiol (3 alpha, 20 alpha) in urine].

PMID- 14955234
TI  - [A hyaluronidase simulating factor in canine saliva].

PMID- 14955235
TI  - [Investigations on purification of gastric cathepsine].

PMID- 14955236
TI  - [Flame photometric determination of calcium in the blood serum].

PMID- 14955237
TI  - [Analysis of pterins].

PMID- 14955238
TI  - [Analysis of proteins in feeds. I. Determination of tryptophan in feeds].

PMID- 14955239
TI  - [A coloring agent of protein nature in the sponge Aplysina aerophoba Nardo].

PMID- 14955240
TI  - [Additional investigations on the inhibition of mitosis by stilbylamine
      derivatives].

PMID- 14955241
TI  - [Biological importance of alpha-oxy-tryptophan].

PMID- 14955242
TI  - Some considerations of factors concerned with blood clotting.

PMID- 14955243
TI  - [Solitary ventricle; case of cor triloculare biatrium with long survival,
      simulating rheumatic heart disease].

PMID- 14955244
TI  - [Pathogenesis of renal tuberculosis; experimental historical data].

PMID- 14955245
TI  - [Chronic myeloid leukemia. III. Clinical therapeutic study in the light of modern
      knowledge].

PMID- 14955246
TI  - [Diagnosis of intestinal parasites; comparative study of the methods of Faust and
      associates, sedimentation and Ferreira e Abreu].

PMID- 14955247
TI  - [Hypoglycemia].

PMID- 14955248
TI  - [Ligature of the inferior vena cava in myocardial infarct with cardiac
      insufficiency; presentation of a case].

PMID- 14955249
TI  - [Cystic fibrosis of the pancreas; case report].

PMID- 14955250
TI  - [More on transcorneal cyclodialysis].

PMID- 14955251
TI  - [Morbid conditions which simulate heart diseases; results of clinical analysis of
      100 cases].

PMID- 14955252
TI  - [BCG vaccination of newborn in Rio de Janeiro, 1927-1951].

PMID- 14955253
TI  - [Treatment of intra-thoracic wounds in the World War II].

PMID- 14955254
TI  - [Method of choice in the dietary treatment of essential arterial hypertension].

PMID- 14955255
TI  - [Examination of the labyrinth in brain lesions].

PMID- 14955256
TI  - [Intravenous novocaine in proctology].

PMID- 14955257
TI  - [Research on Bufo marinus venom].

PMID- 14955258
TI  - [Drug therapy of thyrotoxicosis].

PMID- 14955259
TI  - [Acute rheumatic myocarditis].

PMID- 14955260
TI  - [High fractions of blood iron].

PMID- 14955261
TI  - [Causes of visual disabilities in the selection of air cadets].

PMID- 14955262
TI  - [History of aviation medicine in Brasil].

PMID- 14955263
TI  - [Campaign against tuberculosis in the Federal District].

PMID- 14955264
TI  - [Results of streptomycin and PAS therapy of pulmonary tuberculosis in children].

PMID- 14955265
TI  - [Antibiotics in a tuberculosis clinic in Amazonas].

PMID- 14955266
TI  - [Streptomycin therapy of uncomplicated primary tuberculous complex in children].

PMID- 14955267
TI  - [Serofibrinous pleurisy; early puncture, intrapleural instillation of
      antibiotics].

PMID- 14955268
TI  - [Pneumomediastinum and its occurrence in pulmonary tuberculosis].

PMID- 14955269
TI  - [New pneumothorax and pneumoperitoneum apparatus].

PMID- 14955270
TI  - [Discontinuance of gold treatment in tuberculosis therapy].

PMID- 14955271
TI  - [Psychopathology of tuberculotics].

PMID- 14955272
TI  - [New anti-tuberculosis drugs].

PMID- 14955273
TI  - Studies on the bionomics of Anopheles aquasalis Curry, 1932. Part I.

PMID- 14955274
TI  - Clinical trial of M-5943. (A new chloro derivative of proguanil).

PMID- 14955275
TI  - Action of proguanil and pamaquin, separately and in combination, against P
      knowlesi in S. rhesus monkeys.

PMID- 14955276
TI  - Studies on toxicity of proguanil in S. rhesus monkeys.

PMID- 14955277
TI  - Isolation of strain of P. inui from mixed infection in Malayan monkey.

PMID- 14955278
TI  - Studies on Plasmodium berghei n. sp. Vincke and Lips, 1948. III. Latency, relapse
      and immunity in albino rats with blood-induced infections.

PMID- 14955279
TI  - Studies on plasmodium berghei n. sp. Vincke and Lips, 1948. IV. The reaction of
      blood-induced P. berghei in albino mice to quinine and sulphadiazine.

PMID- 14955280
TI  - Anti-tubercular activity of organic (synthetic) compounds related to PAS in
      vitro.

PMID- 14955281
TI  - An investigation into the relationships between the species (parasitic in man) of
      the genus Leishmania Ross, 1903. Part I. A study of the cultural characters and
      morphology with a statistical analysis of the relative measurements of the
      various species.

PMID- 14955282
TI  - Environmental conditions in printing presses.

PMID- 14955283
TI  - Comfort range in tropical Calcutta; a preliminary experiment.

PMID- 14955284
TI  - Evaluation of lead hazard in a pigment manufacturing concern.

PMID- 14955285
TI  - Antihistaminics in ophidiasis.

PMID- 14955286
TI  - Estimation of stature from clavicle in Punjabis; a preliminary report.

PMID- 14955287
TI  - Amino Amino-acid composition of Indian foodstuffs. Part I. Tryptophan, leucine,
      isoleucine and valine content of some cereals.

PMID- 14955288
TI  - Studies in protein metabolism: creatinine excretion in urine in relation to
      sources of dietary proteins.

PMID- 14955289
TI  - A preliminary note on the pharmacological action of the total alkaloids isolated
      from Cissampelos pareira Linn. (false Pareira brava).

PMID- 14955290
TI  - Studies on Suchikabharana an Ayurvedic tonic preparation of cobra venom.

PMID- 14955291
TI  - Distribution of the natural non-specific synergists in different fractions of
      crude veal-infusion proteose-peptone diphtheria toxoid.

PMID- 14955293
TI  - Studies on rabies. VII. Observations on the paralytogenic factor in rabies
      vaccine.

PMID- 14955292
TI  - Sterility tests of chemical solutions meant for parenteral administration.

PMID- 14955294
TI  - [Dentofacial orthopedics and social security].

PMID- 14955295
TI  - [Dental assistants].

PMID- 14955296
TI  - [A simple method of stabilizing full upper dentures].

PMID- 14955297
TI  - [Historical notes on refrigeration anesthesia].

PMID- 14955298
TI  - [Painless grinding and drilling].

PMID- 14955299
TI  - [Pyorrhea alveolaris and allergy].

PMID- 14955300
TI  - [Presentation of a device for dental refrigeration anesthesia].

PMID- 14955301
TI  - [Effect of tobacco on the oral mucosa in North Africans].

PMID- 14955302
TI  - [All that is dental belongs to us].

PMID- 14955303
TI  - [Metallic subpereosteal implantation in resturation of fixed dental prosthesis].

PMID- 14955304
TI  - [Application of aureomycin into the root canal in therapy of periodontitis].

PMID- 14955305
TI  - [The air bubble].

PMID- 14955306
TI  - [Fundamental principles in the construction of full dental prosthesis].

PMID- 14955307
TI  - [Chinese acupuncture in dentistry].

PMID- 14955308
TI  - [Integral syndesmotomy].

PMID- 14955309
TI  - [A practical instrument to soften the bite block].

PMID- 14955310
TI  - [Neutralization of the effect of local anesthetics by synthetic antihistaminics].

PMID- 14955311
TI  - [Convenient compact for the hygienic upkeep of the teeth and dentures].

PMID- 14955312
TI  - [Acupuncture].

PMID- 14955313
TI  - [Therapy of menstrual diseases of the paradentium with testosterone propionate].

PMID- 14955314
TI  - Nutrition following total gastrectomy, with particular reference to fat and
      protein assimilation.

PMID- 14955315
TI  - [Charles Richet].

PMID- 14955316
TI  - [Nobel conference on anaphylaxy].

PMID- 14955317
TI  - [Intravenous tuberculination in man and animals].

PMID- 14955318
TI  - [Effects of desoxycorticosterone, cortisone and antihistaminics on the
      anaphylactic shock of the adrenalectomized guinea pig].

PMID- 14955319
TI  - [Study of the reticuloendothelial origin of the cells with fine dust or alveolar
      macrophages. III. Their appearance in guinea pig lungs in acetylcholine shock].

PMID- 14955320
TI  - [Critical comparison of therapeutic effects of calcium and antihistaminics in
      therapy of urticaria].

PMID- 14955321
TI  - [Allergy in autochthonic inhabitants of the Bolivian high plane].

PMID- 14955322
TI  - Determinations of the cholesterol content in the blood of allergic patients.

PMID- 14955323
TI  - Prof. Dr. R. Doerr.

PMID- 14955324
TI  - ISRAEL Society of Allergy.

PMID- 14955325
TI  - Bacterial component of bacillus pyocyaneus. VI. Studies on polysaccharides.

PMID- 14955326
TI  - Biological studies on ascaris eggs. I. Comparative study of various culture
      methods of ascaris eggs.

PMID- 14955327
TI  - Redescription of cercaria nipponensis faust, 1924, a xiphidiocercaria in snail
      host semisculcospira spp. in Japan (Trematoda).

PMID- 14955328
TI  - Biological studies on ascaris eggs. II. On the penetrating activity of various
      chemicals of ascaris eggs.

PMID- 14955329
TI  - Quantitative paper chromatographic estimation of various amino acids; a
      modification of Fisher's method.

PMID- 14955330
TI  - Biological studies on Ascaris eggs. II. Appearance and decline of nucleic acid,
      fat and glycogen in consequence of Ascaris oogenesis.

PMID- 14955331
TI  - Hydroxyquinones. XIII. Synthesis of dialkyldihydroxyquinones.

PMID- 14955332
TI  - Some aspects of methanol precipitation of influenza cirus.

PMID- 14955333
TI  - Studies on the development of tuberculin allergy in human bodies inoculated with
      heat-killed BCG suspended in paraffin oil or peanut oil.

PMID- 14955334
TI  - DDT-resistant louse in Tokyo.

PMID- 14955335
TI  - Experimental studies in the treatment of tetanus and on a case of tetanus treated
      with usnic acid.

PMID- 14955336
TI  - A description of two Xiphidiocercariae, Cercaria okabei Ito, 1949, and Cercaria
      of Maritrema caridinae (Cercaria Takahashii yokogawa et Ito, 1949), parasitic in
      Katayama nosophora in Japan (Trematoda).

PMID- 14955337
TI  - Researches on formolgelification of various protein fractions contained in serum,
      with special reference to their change of viscosity in the wide range of pH.

PMID- 14955338
TI  - S. newbrunswick from a food poisoning outbreak and from a healthy carrier.

PMID- 14955339
TI  - The influence of morphine and phenobarbital on the blood content of acetone
      bodies in normal rabbits.

PMID- 14955340
TI  - The effect of diphenhydramine on the human and rabbit electroencephalograms.

PMID- 14955341
TI  - On the mechanism of adrenaline-potentiating action of cocaine.

PMID- 14955342
TI  - Absorption, distribution and excretion of methyl alcohol.

PMID- 14955343
TI  - Studies on enema; on penicillin absorption in large intestine.

PMID- 14955344
TI  - Locomotion of Ascaris suilla et lumbricoides and the influence of anthelminthics
      upon them.

PMID- 14955345
TI  - The mode of action of glycols as vehicles and solvents on the penetration of the
      antibacterial activity of furan derivatives.

PMID- 14955346
TI  - Nitrogenous substances in saliva. 2. Urea and rhodan.

PMID- 14955347
TI  - Studies on the reaction of a single montoneuron in the spinal cord of a toad to
      electrical stimulation.

PMID- 14955348
TI  - Effect of the connective tissue sheath on the value of the accommodation constant
      2 of a nerve fiber.

PMID- 14955349
TI  - Repetitive responses of the nerve fiber, as determined by recovery process and
      accommodation.

PMID- 14955350
TI  - The action of the depressor nerve on the blood vessels of the liver.

PMID- 14955351
TI  - Periodic changes in the liver volume and changes in the portal venous pressure.

PMID- 14955352
TI  - Influence of a large amount of sodium chloride ingestion on the basal metabolism
      and on resistance to cold and frost-bite.

PMID- 14955353
TI  - Studies on the reactivity of skin vessels to extreme cold. III. Effects of diets
      on the reactivity of skin vessels to cold.

PMID- 14955354
TI  - The mechanism of the nervous regulation of the respiratory movements.

PMID- 14955355
TI  - The distribution of sensory spots on the oral mucous membrane.

PMID- 14955357
TI  - [Post-traumatic nerve reflex syndromes].

PMID- 14955356
TI  - [Constitution and chronic schizophrenia; preliminary study on research on
      constitution in an unselected series of 100 cases from northern Portugal].

PMID- 14955358
TI  - [Human personality. X..].

PMID- 14955359
TI  - [14th Congress of the International Society of Surgery].

PMID- 14955360
TI  - [Induction of Prof. Mario Trincao to the Chair of General Pathology at Coimbra].

PMID- 14955361
TI  - [Historical notes on ophthalmoscopy].

PMID- 14955362
TI  - [Progress of ophthalmoscopy].

PMID- 14955363
TI  - [Professor Vicente Jose de Carvalho; on the centenary of his death].

PMID- 14955364
TI  - [Scientific research in France].

PMID- 14955365
TI  - [Mitsuda and Bargher reactions in leprosy].

PMID- 14955366
TI  - [Problems of medical secrecy].

PMID- 14955367
TI  - [New application of photoelectricity to physiology and the diagnosis of pulmonary
      cancer].

PMID- 14955368
TI  - [Impressions of a study tour to the Scandinavian countries, Holland and Belgium;
      note on the 14th International Congress of Surgery held at Paris].

PMID- 14955370
TI  - [International Oto-neuro-ophthalmological Congress].

PMID- 14955369
TI  - [Controlled ossification].

PMID- 14955371
TI  - [Ophthalmoscopy in internal medicine].

PMID- 14955372
TI  - [Industrial medicine; various aspects and recommendations].

PMID- 14955373
TI  - [Campaign against tuberculosis in Oporto and Coimbra; inauguration of the
      Prevention and Diagnosis Centers].

PMID- 14955374
TI  - [Ophthalmoscopy in degenerative diseases of the nervous system].

PMID- 14955375
TI  - [Ophthalmoscopy in intracranial hypertension].

PMID- 14955376
TI  - [Intra-arterial oxygen injections; new method of diagnosis and treatment of
      arteritis of the extremities].

PMID- 14955377
TI  - [Medicine and music. VIII. Prof. Orfila].

PMID- 14955378
TI  - [Municipal physicians].

PMID- 14955379
TI  - [Fetal and mortality, 1946-8 and 1949].

PMID- 14955380
TI  - [Case of circumscribed hematoma of the rectus abdominis muscles].

PMID- 14955381
TI  - [Cholera epidemic in the Paraaba Valley].

PMID- 14955382
TI  - [Case of temporary diabetes].

PMID- 14955383
TI  - [Science has almost conquered tuberculosis].

PMID- 14955384
TI  - Dental amalgam; the effect of mechanical condensation on some physical
      properties.

PMID- 14955385
TI  - The influence of systemic diseases on alveolar bone.

PMID- 14955386
TI  - Movements of the condyle from rest position to initial contact and full
      occlusion.

PMID- 14955387
TI  - Combination of antibiotics and fungicides used in treatment of the infected
      pulpless tooth.

PMID- 14955388
TI  - Role of prophylactic procedures in the treatment of periodontal disease.

PMID- 14955389
TI  - Practical use of the space maintainer.

PMID- 14955390
TI  - Some periodontal considerations in partial denture planning.

PMID- 14955391
TI  - Epidemiology of gingivitis in children.

PMID- 14955392
TI  - The organic compounds and enzymes of human saliva.

PMID- 14955393
TI  - An analysis of the Delaney Committee report on the fluoridation of drinking
      water.

PMID- 14955394
TI  - How much otolaryngology should be taught to general practitioners?

PMID- 14955395
TI  - American students in foreign medical schools.

PMID- 14955396
TI  - Wound ballistics and body armor.

PMID- 14955397
TI  - Treatment of alcoholism with antabuse.

PMID- 14955398
TI  - Survey of clotting tests for coagulation profile in normal and diseased persons.

PMID- 14955400
TI  - Rupture of the aortic valve.

PMID- 14955399
TI  - Care of the dying.

PMID- 14955401
TI  - Craniopagus twins; report of a case.

PMID- 14955402
TI  - Failure of corticotropin to prevent acute hemolytic anemia due to sulfapyridine.

PMID- 14955403
TI  - Amyloid tumor of the urinary bladder.

PMID- 14955404
TI  - Medical education in the United States and Canada; fifty-second annual report on
      medical education in the United States and Canada by the Council on Medical
      Education and Hospitals of the American Medical Association.

PMID- 14955405
TI  - APPROVED medical schools in the United States.

PMID- 14955406
TI  - APPROVED medical schools in Canada.

PMID- 14955407
TI  - FIFTY-SECOND annual report on medical education.

PMID- 14955408
TI  - NEW trends in clinical teaching.

PMID- 14955409
TI  - Army medicine in Europe.

PMID- 14955410
TI  - Responsibility of ophthalmologists in era of social revolution.

PMID- 14955411
TI  - The Council on Physical Medicine and Rehabilitation.

PMID- 14955413
TI  - Substitute for urinary bladder.

PMID- 14955412
TI  - Psychiatric symptoms associated with lesions of temporal lobe.

PMID- 14955414
TI  - Incidence and clinical significance of transpyloric prolapse of gastric mucosa.

PMID- 14955415
TI  - Primary adenocarcinoma of the appendix.

PMID- 14955416
TI  - Comparison of the tolerance of adults and children to digitoxin.

PMID- 14955417
TI  - The frequency of functional heart disturbances; a study of 1,000 consecutive
      private cardiac patients.

PMID- 14955418
TI  - Human albumin infusions and homologous serum jaundice.

PMID- 14955419
TI  - The growing problem of chronic disease among the aged.

PMID- 14955420
TI  - Third generation follow-up in woman receiving pelvic irradiation.

PMID- 14955421
TI  - Spontaneous fracture of sternum in tuberculosis.

PMID- 14955422
TI  - Transverse band pigmentation of fingernails after X-ray therapy.

PMID- 14955423
TI  - Hiatus pneumocele complicating therapeutic pneumoperitoneum; report of a case.

PMID- 14955424
TI  - Cancer of male urethra diagnosed by sponge biopsy; report of a case.

PMID- 14955425
TI  - Cardiac arrest and resuscitation during repair of diaphragmatic hernia in infant.

PMID- 14955426
TI  - Disseminated coccidioidomycosis; report of a case in the New England area.

PMID- 14955427
TI  - Psittacosis (ornithosis) following contact with pheasants; report of a case.

PMID- 14955428
TI  - COLLAGEN diseases.

PMID- 14955429
TI  - RETROLENTAL fibroplasia--an unsolved problem.

PMID- 14955430
TI  - Federal Caustic Poison Law.

PMID- 14955431
TI  - MEDICAL care for the indigent in Shawnee County (Topeka), Kansas.

PMID- 14955433
TI  - PSYCHIATRIC examination: right of accused to private examination.

PMID- 14955432
TI  - OPTOMETRY practice acts: classification of schools by private association.

PMID- 14955434
TI  - Prognosis of angina pectoris; observations in 6,882 cases.

PMID- 14955435
TI  - Rapid diagnostic test for myasthenia gravis: increased muscle strength, without
      fasciculations, after intravenous administration of edrophonium (tensilon)
      chloride.

PMID- 14955436
TI  - Acute phase of Japanese B encephalitis; two hundred and one cases in American
      soldiers, Korea, 1950.

PMID- 14955437
TI  - Head lowering in treatment of hypotension.

PMID- 14955438
TI  - Approved internships and residencies in the United States; annual report of
      internships and residencies by the Council on Medical Education and Hospitals of
      the American Medical Association.

PMID- 14955439
TI  - APPROVED internships: Council on Medical Education and Hospitals of the American
      Medical Association revised to September 1, 1952.

PMID- 14955440
TI  - APPROVED residencies and fellowships: Council on Medical Education and Hospitals
      of the American Medical Association revised to September 1, 1952.

PMID- 14955441
TI  - GRADUATE training programs acceptable by the American Board of Psychiatry and
      Neurology.

PMID- 14955442
TI  - APPROVED examining boards in medical specialties: Advisory Board for Medical
      Specialties.

PMID- 14955443
TI  - ANNUAL report of internships and residencies.

PMID- 14955444
TI  - PATENT ductus arteriosus and maternal rubella.

PMID- 14955445
TI  - CHARITABLE hospitals: liability for nurse's negligence.

PMID- 14955446
TI  - Lymphosarcoma of the gastrointestinal tract.

PMID- 14955447
TI  - Hidden or unsuspected bronchiectasis in the asthmatic patient.

PMID- 14955448
TI  - Pyloric stenosis secondary to hydrochloric acid ingestion; report of two cases in
      which hepatitis developed.

PMID- 14955449
TI  - Simultaneous independent paroxysmal tachycardias.

PMID- 14955450
TI  - Clinical use of extracorporeal oxygenation with oxygenator-pump.

PMID- 14955451
TI  - White blood cell changes in clinical disorders.

PMID- 14955452
TI  - Selection of patients for surgical procedures in chronic suppurative otitis
      media.

PMID- 14955453
TI  - Pollen and mold allergy in the Southwest.

PMID- 14955454
TI  - Aureomycin in mumps.

PMID- 14955455
TI  - Biologically false positive serologic tests for syphilis; type, incidence, and
      cause.

PMID- 14955456
TI  - The patient with upper gastrointestinal tract hemorrhage.

PMID- 14955457
TI  - Postmortem observations twenty years after bilateral mastectomy.

PMID- 14955458
TI  - Paroxysmal ventricular tachycardia due to emotion; possible mechanism of death
      from fright.

PMID- 14955459
TI  - Chronic illness and senescence.

PMID- 14955461
TI  - KIDDE tubual insufflator, Office Model No. 605700.

PMID- 14955460
TI  - F. C. C. rules for diathermy equipment manufactured prior to July 1, 1947:
      postponement of effective date of compliance.

PMID- 14955462
TI  - NEW and nonofficial remedies: methorphinan hydrobromide.

PMID- 14955463
TI  - NEW and nonofficial remedies: potassic saline.

PMID- 14955464
TI  - FOCAL infection.

PMID- 14955465
TI  - TRAFFIC accidents.

PMID- 14955466
TI  - MORTALITY reductions during a half century.

PMID- 14955467
TI  - PARTICIPATION in election campaigns.

PMID- 14955468
TI  - Sterility of marker cotton.

PMID- 14955470
TI  - FEE splitting and the income tax law.

PMID- 14955469
TI  - Mortality trends in the United States, 1900-1949.

PMID- 14955471
TI  - The synthesis of some substituted pyridine and piperidine compounds from
      dipicolinic acid.

PMID- 14955472
TI  - A preliminary phytochemical study of Tillandsia usneoides L. (Spanish moss).

PMID- 14955473
TI  - Antispasmodics. I. Phenyl esters of beta-dialkylaminopropionic acids.

PMID- 14955474
TI  - Further studies on the bioassay of Veratrum viride.

PMID- 14955475
TI  - Determination of heavy metals in pharmaceutical chemicals.

PMID- 14955476
TI  - The manufacture of compressed soluble tablets.

PMID- 14955477
TI  - Filter technique as a factor in the stability of thiamine hydrochloride
      injections.

PMID- 14955478
TI  - Preparation and storage of autoclaved pectin solutions.

PMID- 14955479
TI  - Certain substituted thiobisacetamic acids and their salts.

PMID- 14955480
TI  - A simple method for the determination of organic bound iodine.

PMID- 14955481
TI  - The arginase-alkaloid relationship in Datura tatula L.

PMID- 14955482
TI  - The colorimetric determination of salicylates.

PMID- 14955483
TI  - A polarographic study of some Veratrum viride alkaloids.

PMID- 14955484
TI  - Synthesis of mersalyl analogs.

PMID- 14955485
TI  - The determination of histamine in pharmaceutical products by means of 2,4
      dinitrofluorobenzene.

PMID- 14955486
TI  - A colorimetric assay for pilocarpine and its salts.

PMID- 14955487
TI  - The determination of carvone in oil of spearmint.

PMID- 14955488
TI  - A note on an apparatus for prolonged and repeated intravenous infusions in large
      animals.

PMID- 14955489
TI  - Comparison of the metabolism of ammonia and molecular nitrogen in
      photosynthesizing bacteria.

PMID- 14955490
TI  - Lactic acid fermentation of xylose by escherichia coli. I. Fermentation studies.

PMID- 14955491
TI  - Lactic acid fermentation of xylose by escherichia coli. II. Tracer studies;
      evidence for C2+C1 condensation.

PMID- 14955492
TI  - Reduction of the x-ray sensitivity of escherichia coli by sodium hydrosulfite and
      certain other inorganic sulfur compounds.

PMID- 14955493
TI  - The action of some members of the genus serratia on egg yolk complex.

PMID- 14955494
TI  - Respiratory activity of cell-free extracts from azotobacter.

PMID- 14955495
TI  - The effect of oxalacetate on the oxidation of succinate by azotobacter extracts.

PMID- 14955496
TI  - Development of increased bacterial resistance to antibiotics. I. Continuous
      spectrum of resistance to penicillin, chloramphenicol, and streptomycin.

PMID- 14955497
TI  - Studies on bacterial reducing activity in relation to age of culture.

PMID- 14955498
TI  - Observations on the growth of escherichia coli in media containing amino acids as
      the sole source of nitrogen.

PMID- 14955499
TI  - Preparation and properties of cell-free "formic hydrogenlyase" from escherichia
      coli.

PMID- 14955500
TI  - Factors affecting the lytic activity of lysozyme.

PMID- 14955501
TI  - The irreversibility of methionine synthesis from cysteine in pasteurella pestis.

PMID- 14955502
TI  - Effect of the isomeric configuration of the source of nitrogen on changes in
      population and metabolism in cultures of Brucella.

PMID- 14955503
TI  - Photoreversal of the lengthening effect of ultraviolet radiations on the
      bacterial lag period.

PMID- 14955504
TI  - Variation of irradiation effects on microorganisms in relation to physical
      changes of their environment.

PMID- 14955505
TI  - Further use of diphenylamine for the study of carotenoid biosynthesis in
      mycobacterium phlei.

PMID- 14955506
TI  - A simplified medium for the production of streptolysin OI.

PMID- 14955507
TI  - Effect of subtilin on spores of clostridium botulinum.

PMID- 14955508
TI  - Requirements for formic hydrogenlyase adaptation in nonproliferating suspensions
      of escherichia coli.

PMID- 14955509
TI  - The effect of terramycin on the antagonism of certain bacteria against species of
      proteus.

PMID- 14955510
TI  - Studies on the carbon dioxide requirement of Neisseria meningitidis.

PMID- 14955512
TI  - On the culture and general physiology of the green sulfur bacteria.

PMID- 14955511
TI  - Orcein stain for bacterial chromatinic material.

PMID- 14955513
TI  - Studies on the aerobic oxidation of fatty acids by bacteria. III. The effect of
      2,4-dinitrophenol on the oxidation of fatty acids by Serratia marcescens.

PMID- 14955514
TI  - The inhibition of enzyme formation by amino acid analogues.

PMID- 14955515
TI  - Carbon dioxide fixation into amino acids of penicillium chrysogenum.

PMID- 14955516
TI  - Studies of dengue fever virus by electron microscopy.

PMID- 14955517
TI  - Physical properties of two group of coxsackie (herpangina) viruses when
      propagated in eggs and mice as determined by ultracentrifugation and electron
      microscopy.

PMID- 14955518
TI  - Substrate oxidation and nitrous oxide utilization in denitrification.

PMID- 14955519
TI  - A rapid method for identification of newly isolated influenza viruses.

PMID- 14955520
TI  - Fermentation of galacturonic acid and glucose by a strain of erwinia carotovora.

PMID- 14955521
TI  - The nutritional requirements of Treponemata. III. A defined medium for
      cultivation of the Reiter treponeme.

PMID- 14955522
TI  - On the decomposition of pyrimidines by bacteria. I. Studies by means of the
      technique of simultaneous adaptation.

PMID- 14955523
TI  - On the decomposition of pyrimidines by bacteria. II. Studies with cell-free
      enzyme preparations.

PMID- 14955524
TI  - [Syndrome of post-operative deficiency of potassium].

PMID- 14955525
TI  - [Possibilities and limitations of chemical and pharmacological methods to open
      the common bile duct].

PMID- 14955526
TI  - Blood pyruvic acid response to intravenous glucose or insulin in the normal and
      in patients with liver disease and with diabetes mellitus.

PMID- 14955527
TI  - Metabolism of pteroylglutamic acid and the citrovorum factor in patients with
      scurvy.

PMID- 14955528
TI  - Cardiac failure secondary to ineffective bellows action of the chest cage.

PMID- 14955529
TI  - Effects of acute anoxia on the circulation and respiration in patients with
      chronic pulmonary disease studied during the steady state.

PMID- 14955530
TI  - The reactivity of the capillary bed of the nailfold to circulating epinephrine
      and nor-epinephrine in patients with normal blood pressure and with essential
      hypertension.

PMID- 14955531
TI  - Thyroid function in nephrosis.

PMID- 14955532
TI  - The extrarenal correction of alkalosis associated with potassium deficiency.

PMID- 14955533
TI  - Primary epithelial tumours of the jaw.

PMID- 14955534
TI  - Lower nephron nephrosis after transurethral resection of the prostate.

PMID- 14955535
TI  - Anisotropic non-silicious crystalline inclusions in a dysgerminoma of tuberculoid
      appearance.

PMID- 14955536
TI  - The histological changes in hydantoinate gingivitis.

PMID- 14955537
TI  - The value of rib biopsy in the study of marrow disorders.

PMID- 14955538
TI  - Vitamin B12 assay in body fluids using Euglena gracilis.

PMID- 14955539
TI  - The construction and clinical significance of the coagulohepatogram.

PMID- 14955540
TI  - The relation between polyagglutinability of erythrocytes in vivo and the Hubener
      Thomsen-Friedenreich phenomenon.

PMID- 14955541
TI  - Determination of the unsaturated iron-binding capacity of serum.

PMID- 14955542
TI  - The application of a haemagglutination technique to the study of Trichomonas
      vaginalis infections.

PMID- 14955543
TI  - The relationship between iron storage and anaemia.

PMID- 14955544
TI  - The effect of photo-electric cell temperature on flame photometer determinations.

PMID- 14955545
TI  - A rapid method for determining faecal fat.

PMID- 14955546
TI  - A simple method for the aseptic filling of screw-capped containers.

PMID- 14955547
TI  - A direct scanning apparatus for reading electrophoretic paper strips.

PMID- 14955548
TI  - The ovarian control of the hypophysial gonadotrophic function.

PMID- 14955549
TI  - Some observations on the Kober colour and fluorescence reactions of the natural
      oestrogens.

PMID- 14955550
TI  - The effect of high doses of ascorbic acid on the functions of the adrenal glands.

PMID- 14955551
TI  - The action and fate of vasopressin in newborn and infant rats.

PMID- 14955552
TI  - The assay of small amounts of antidiuretic activity by intravenous injections
      into mice.

PMID- 14955553
TI  - The effect of hypothyroidism on the guinea-pig.

PMID- 14955554
TI  - A transpalatal approach to the hypothalamic area in the ferret.

PMID- 14955555
TI  - Observations on the relationship between oxytocin and adrenaline in milk ejection
      in the sow.

PMID- 14955556
TI  - A comparison of plasma inorganic phosphate levels in normal and diabetic
      pregnancies.

PMID- 14955557
TI  - The mechanism of the protective action of clamping the renal pedicles of dogs
      with alloxan diabetes.

PMID- 14955558
TI  - The effect of exogenous thyroxine on radioiodine uptake in normal subjects and in
      cases of thyrotoxicosis in remission.

PMID- 14955559
TI  - Relaxation of the pelvis in guinea-pigs following implantation of pituitary
      glands.

PMID- 14955560
TI  - Studies on the metabolism of adrenal steroid hormones.

PMID- 14955562
TI  - PROCEEDINGS of the society for endocrinology; twenty-eighth ordinary meeting.

PMID- 14955561
TI  - Stress and epidermal mitotic activity. I. The effects of the adrenal hormones.

PMID- 14955563
TI  - Nursing behaviour and the milk ejection reflex in rabbits.

PMID- 14955564
TI  - Assay of ACTH on the thymus of the young rat.

PMID- 14955565
TI  - Comparison of the effects of methyl testosterone and desoxycorticosterone on
      electrolytes.

PMID- 14955566
TI  - The effect of ACTH on gonadotrophic action.

PMID- 14955567
TI  - The formation of collagen fibers by the action of heparin on soluble collagen: an
      electron microscope study.
AB  - Collagen fibers have been formed in vitro by the action of heparm on solutions of
      collagen. Heparin was found to be effective in inducing collagen fiber formation
      when present in concentrations as low as 1-80,000. It is postulated that mast
      cells, by virtue of the heparin which they produce, may play a role in the
      formation of collagen.

PMID- 14955568
TI  - The influence of diet on iron absorption. III. Comparative studies with rats,
      mice, guinea pigs, and chickens.
AB  - The response of rats, chicks, mice, and guinea pigs to two diets containing
      various amounts of iron has been compared. With diets composed chiefly of corn
      grits animals of all these species absorb and store considerably more iron than
      those with normal diets of the same iron content. If sufficient iron is added to
      a normal diet, all species will absorb large amounts of iron. However, there
      appear to be great species differences in the level of iron which must be fed to
      cause the increase in absorption. Chicks and mice appear to have less effective
      control over iron absorption on high iron diets. Attention is called to large
      individual differences in ability to control iron absorption under the conditions
      of these experiments.

PMID- 14955569
TI  - The intracellular distribution of Lansing poliomyelitis virus in the central
      nervous system of infected cotton rats.
AB  - A procedure has been described for the centrifugal fractionation of the cellular
      particulate components of CNS tissue infected with poliomyelitis virus. A study
      of the distribution of infectivity among these components revealed that
      approximately four-fifths of the virus is found free in the submicroscopic
      particle fraction. The validity of the conclusion that the virus is located in
      this fraction of the intact neuron is discussed.

PMID- 14955570
TI  - The multiplication of tubercle bacilli within normal phagocytes in tissue
      culture.
AB  - A technique has been described for the cultivation in vitro of normal mononuclear
      cells on glass slides in a liquid medium. Under these conditions the monocytes
      transformed into macrophages which proliferated as in ordinary tissue culture.
      These cultures of monocytes could be infected with tubercle bacilli. The numbers
      of stainable tubercle bacilli within the monocytes increased steadily in cultures
      infected with virulent or attenuated strains. Evidence is given to support the
      view that this increase in numbers of bacilli was due to intracellular
      multiplication. There was no evidence of intracellular bacillary multiplication
      in cultures infected with an avirulent strain. Tubercle bacilli multiplying
      within phagocytes in vitro exert a damaging effect upon the host cells. The
      damage was most obvious in cells infected with a virulent strain. Tubercle
      bacilli within phagocytes were protected against the bacteriostatic effect of
      streptomycin added in a concentration of 5 gamma per ml. of culture medium. This
      permitted the use of streptomycin in infected cultures to prevent extracellular
      multiplication of the bacilli.

PMID- 14955571
TI  - The relation of herpes virus to host cell mitochondria.
AB  - The intracellular distribution of herpes virus in embryonic liver was
      investigated. 80 per cent of the virus was found in the cytoplasm in what appears
      to be a form uncombined with mitochondria or nuclei. A significant amount of the
      virus (16 per cent) was found bound to the mitochondria by an intimate
      attachment. Furthermore evidence was obtained that the mitochondria from liver
      tissue undergo a selective deterioration when infected with herpes virus. The
      concept is advanced that these organelles function in the development of virus.

PMID- 14955572
TI  - Experiments on the cause of the rabbit carcinomas derived from virus-induced
      papillomas. II. Loss by the Vx2 carcinoma of the power to immunize hosts against
      the papilloma virus.
AB  - Tests were made to learn whether an anaplastic, epidermal carcinoma, the Vx2,
      which had originated more than 8 years previously from a virus papilloma in a
      domestic rabbit, still rendered its hosts immune to the virus. It had done so in
      the first 22 successive groups of animals to which it was transferred during a
      period of 3(1/2) years, its growth regularly eliciting a blood antibody that
      neutralized the Shope virus and fixed complement in mixture with it; and on the
      assumption that this would continue to be the case no further observations were
      made for nearly 4(1/2) years more. Then direct inoculation of animals carrying
      the tumor in its 46th Generation showed them to be as susceptible to the virus as
      normal rabbits; and sera procured from hosts of the 46th, 47th, 48th, and 50th
      Generations failed to neutralize the virus or fix complement with it. Tests of
      this last sort, repeated at intervals since,-most recently with sera from animals
      carrying the tumor in its 73rd Generation,-have yielded consistently negative
      findings. Loss of the power to immunize against the papilloma virus was not
      attended by any perceptible change in the Vx2 carcinoma. Manifestly the antigen
      responsible for the immunity cannot, as such, have been the actuating cause of
      the tumor. Attempts were made to infect the cells providing 48th Generation
      cancers, by mixing them with a suspension of the papilloma virus at time of
      implantation, or by injecting this agent into the blood stream of rabbits in
      which the tumog had already begun to proliferate. Its morphology and rate of
      growth remained unaltered; but tests of the animals to which transfers were next
      made yielded what appeared to be evidence of some slight immunity to the virus.

PMID- 14955573
TI  - Complement-fixing antibodies to type 2 (Lansing) poliomyelitis virus in a normal
      population of a subtropical area.
AB  - Sera collected in 1950 from the native population in the vicinity of Cairo,
      Egypt, have been tested for complement-fixing antibodies to Type 2 (Lansing)
      poliomyelitis virus. Complement-fixing antibodies are confined to the age of 1 to
      9 years if a serum dilution of 1:4 is used in the test, or to the age of 1 to 4
      years with a serum dilution of 1:16. A comparison has been made of the findings
      obtained in this study with the results for neutralizing antibodies previously
      reported. Complement-fixing antibodies were found to be temporary in nature while
      neutralizing antibodies were maintained for long periods of time. On this basis,
      criteria for "recent," "old," or "no infection" in poliomyelitis have been
      established. Sixteen of the children were bled again in 1952, 18 months after the
      first bleeding and both series of sera were compared in complement fixation and
      neutralization tests. All children who were negative in 1950 and who developed c
      f antibodies by 1952, also developed neutralizing antibodies to a titer of more
      than 1:250 during the same period. Some children who failed to develop c-f
      antibodies, did develop neutralizing antibodies although of lower titer than
      found in children in whom c-f antibodies made their appearance. These findings
      are discussed in the light of theories regarding the mode of acquisition of
      antibodies to poliomyelitis virus.

PMID- 14955574
TI  - Induction of arterial hypertension in normal and adrenalectomized rats given
      cortisone acetate.
AB  - 1. Marked hypertension was induced in adrenalectomized rats on a sodium
      restricted intake by the administration of cortisone acetate; on a similar
      regimen, adrenalectomized rats receiving DCA failed to become hypertensive. 2.
      The incorporation of a liberal amount of sodium in the diet of adrenalectomized
      rats receiving cortisone acetate resulted in a lesser degree of hypertension;
      whereas on a similar regimen, DCA-injected animals became strikingly
      hypertensive, as has been previously reported. 3. The presence of hypertension in
      the cortisone acetate-treated rats was not associated with histological evidence
      of renal damage or serum electrolyte disturbance, such as was observed in
      hypertensive animals receiving DCA. 4. The hypertension in sodium-restricted
      normal rats receiving cortisone acetate was less striking than in similarly
      treated adrenalectomized animals. On a liberal sodium intake similar degrees of
      hypertension were noted in both intact and adrenalectomized groups. 5. To
      approximate the loss of weight which occurred in cortisone acetate-injected rats,
      it was necessary to curtail the food intake of partially fasted control groups to
      50 to 75 per cent of the amount consumed by the animals receiving the steroid. 6.
      The serum cholesterol levels of the cortisone acetate-injected rats were
      consistently and strikingly elevated as contrasted with normal, partially fasted,
      or DCA-treated animals.

PMID- 14955575
TI  - Growth requirements of dysgonic and eugonic strains of Mycobacterium tuberculosis
      var. bovis.
AB  - The nutritional requirements of dysgonic and eugonic bovine tubercle bacilli were
      investigated in liquid Tween-albumin medium. The following conclusions were
      reached:- Dysgonic bovine tubercle bacilli require for multiplication long chain
      fatty acids which can be supplied as oleic, palmitic, or stearic acid whereas
      eugonic bovine strains can grow in the absence of fatty acid and can utilize
      glucose as a sufficient source of carbon. In the presence of fatty acids, the
      growth of dysgonic strains is increased by the addition of small amounts of
      glucose or glycerol, whereas large amounts of glucose or glycerol decrease the
      total growth and inhibit or retard the growth of small inocula. In glucose-fatty
      acid media, the growth of dysgonic strains is further stimulated by the addition
      of sodium glutamate, succinate, malate, or acetate. Sodium pyruvate enables
      dysgonic strains to grow rapidly in liquid media containing glucose or glycerol
      even in the absence of fatty acid. The significance of these findings for the
      mechanism of the variation from "dysgonic" to "eugonic" is discussed. The use of
      oleic acid-albumin agar without glucose permits the rapid isolation of bovine
      tubercle bacilli from natural sources.

PMID- 14955576
TI  - The relative effects of protein, choline, and methionine in the treatment of
      experimental dietary cirrhosis in the rat.
AB  - Cirrhosis of the liver was produced in rats by feeding a diet low in protein (4
      per cent casein) and deficient in lipotropic factors. The degree of liver
      cirrhosis was determined from specimens obtained at biopsy. Comparable groups of
      animals then were treated with diets containing 4 per cent casein and 30 per cent
      casein. The 4 per cent casein diets were supplemented with choline and
      methionine; the 30 per cent casein diets were fed with and without added choline.
      On supplementing the low protein diet with choline and methionine the animals
      remained feeble, their growth remained stunted, and their livers showed signs of
      progressive cirrhosis. In contrast, animals fed the higher protein diet (with or
      without added choline) grew normally, and their livers showed signs indicating
      arrest and regression of the disease process. These studies suggest that the
      feeding of high protein (30 per cent casein) diets to rats with nutritional
      cirrhosis produces reparative effects greater than those attributable to the
      supplements choline and methionine.

PMID- 14955577
TI  - Studies on the psittacosis-lymphogranuloma group. II. A non-infectious phase in
      virus development following adsorption to host tissue.
AB  - The pattern of growth of meningopneumonitis virus in vitro seemed to be similar
      to that occurring in ovo and thus the initial stages of development, the
      adsorption and the latent periods, were investigated by the use of tissue culture
      procedures. The initial increment of infectivity in allantoic membrane
      suspensions following virus inoculation in ovo was due to prolonged adsorption of
      virus and not to immediate virus reproduction. The length of the adsorption
      period varied with the virus dilution employed. The reduction of virus titer in
      allantoic membrane suspensions subsequent to adsorption was due to a change of
      infectious virus to a non-infectious form and this seemed to be a part of the
      normal developmental cycle of the virus. The possible causes for both prolonged
      virus adsorption and for the subsequent development of a non-infectious form are
      discussed.

PMID- 14955578
TI  - Plasma protein labeled with lysine-epsilon-C14; its oral feeding and related
      protein metabolism in the dog.
AB  - The metabolism of homologous plasma proteins, labeled with lysine-epsilon-C(14),
      after oral administration to dogs has been investigated. The speed of the various
      processes involved is indicated by the maximum rate of C(14) O(2) excretion which
      is attained within 1 to 4 hours, the prompt appearance of protein activity in the
      plasma and disappearance of non-protein activity from it, both virtually complete
      in 7 to 10 hours, as well as the rapid incorporation of a large percentage of the
      fed-C(14) into tissues. There are no essential differences between the behavior
      of labeled plasma and that of an amino acid digest containing epsilon-C(14)
      labeled lysine when these two materials are given orally. At the end of 48 hours
      after labeled plasma feeding, a CO(2) elimination of 16 to 28 per cent of the fed
      C(14) is noted. In contrast, after 48 hours following labeled plasma by vein, a
      CO(2) elimination of only 2.5 per cent is recorded-almost a 10 to 1 ratio. We
      believe this, together with the data concerning plasma and tissue protein
      activity, represents a significant difference in the metabolic process. The
      evidence favors a complete breakdown of plasma protein to the amino acid level
      when given orally but not when given by vein.

PMID- 14955579
TI  - The survival of poliomyelitis and Coxsackie viruses following their ingestion by
      flies.
AB  - Poliomyelitis virus and Coxsackie (or C) virus were quantitatively fed to
      blowflies, Phormia regina and Phaenicia sericata, and to houseflies, Musca
      domestica. Naturally infectious human stools were the source of virus.
      Poliomyelitis virus can be almost quantitatively recovered from flies and from
      their excreta collected over a period of several days following the feeding. C
      virus can also be recovered but in lesser yields. No conclusive evidence for
      virus multiplication in these laboratory-bred insects was obtained. Poliomyelitis
      virus from human sources could be detected in flies between the 5th and 17th day
      and in the excreta between the 4th and 10th day. Murine-adapted strains of
      poliomyelitis virus and murine encephalomyelitis virus could not be detected
      beyond the 5th day, even though comparable amounts of virus were fed. The
      persistence of C virus excretion (2 to 12 days) varied directly with the amount
      of virus fed. Poliomyelitis virus, as present in human stools, survived drying
      and storage at room temperature for at least 3 days and at 4 degrees for 3 weeks.
      C virus from human stools under the same circumstances was detected for 15 days
      at room temperature (with marked drop in titer after the 3rd day) and for 21 days
      at 4 degrees with little loss in titer. When stool samples were fed to flies and
      the dried excreta of the insects examined, it was found that (a) poliomyelitis
      virus persisted for at least 1 to 2 days at room temperature and for 3 to 4 days
      at 4 degrees , and (b) C virus persisted for 1 day at room temperature and for 5
      days at 4 degrees . Poliomyelitis virus could be carried through only two serial
      passages in adult flies. Flies emerging from maggots fed virus were free from the
      agent.

PMID- 14955580
TI  - Methods for following the fate of infectious agents fed to single flies.
AB  - Methods have been devised which facilitate the handling, feeding, and collection
      of excreta from individual flies bred in the laboratory. Using these methods,
      quantitative studies can be carried out in which known amounts of infectious
      material are fed to flies and the fate of these agents determined. It has been
      possible to determine the persistence of excretion of viruses, and the amount of
      the ingested virus recovered in the excreta and in the bodies of the flies as
      well.

PMID- 14955581
TI  - Studies of the effect of change of drive. II. From hunger to different
      intensities of a thirst drive in a t-maze.

PMID- 14955582
TI  - The role of the vestibular organs in space orientation.

PMID- 14955583
TI  - The perceived slant of visual surfaces-optical and geographical.

PMID- 14955585
TI  - Acquisition and retention of three psychomotor tests as a function of
      distribution of practice during acquisition.

PMID- 14955584
TI  - Does motion perspective independently produce the impression of a receding
      surface?

PMID- 14955586
TI  - A criticism of pre-acquisition and pre-extinction of expectancies.

PMID- 14955587
TI  - Experimental studies in rote-learning theory: X. Pre-learning syllable
      familiarization and the length-difficulty relationship.

PMID- 14955588
TI  - An experimental note on a Hull-Leeper difference.

PMID- 14955589
TI  - Retroactive facilitation and interference in performance on the modified two-hand
      coordinator.

PMID- 14955590
TI  - Listening to one of two synchronous messages.

PMID- 14955591
TI  - Location of objects in a visual display as a function of the number of dimensions
      on which the objects differ.

PMID- 14955592
TI  - [Six cases of cystic pulmonary sequestration with abnormal artery of aortic
      origin].

PMID- 14955593
TI  - [The nosological place of bronchial epistomas (epitheliomas with modified
      stroma)].

PMID- 14955594
TI  - [Some forms of epistomas with malignant development].

PMID- 14955595
TI  - [Intrabronchial metallic foreign body (bomb burst) simulating a hilar
      calcification discovered 36 years after a facial wound received in the war].

PMID- 14955596
TI  - [Pulmonary forms of Besnier-Boeck-Schaumann disease].

PMID- 14955597
TI  - [Isolation of Francois-Heglin syndrome; biological reactions of atypical
      pneumonias: cold agglutinins, syphilis blood tests and Hirst reaction].

PMID- 14955598
TI  - [Degenerated polyp; single pulmonary metastatic focus; exeresis; recovery].

PMID- 14955599
TI  - [Benign tumor of the left bronchus (hamartoma?) treated with bronchotomy after
      extemporaneous biopsy].

PMID- 14955600
TI  - [Probable Besnier-Boeck disease with strictly pulmonary localization, complicated
      after five years by cavitary tuberculosis, and cured by extra-pleural
      pneumothorax].

PMID- 14955601
TI  - [Bronchial infection in asthma].

PMID- 14955602
TI  - [Bronchiectasis caused by aspergillosis].

PMID- 14955603
TI  - [A case of hernia diaphragmatics (partial agenesis of the left diaphragm).
      Plastic surgery of the diaphragm with the primarily atelectatic lung].

PMID- 14955604
TI  - [Presence of occluded segments and glomi in the wall of bronchiectasis].

PMID- 14955605
TI  - [Chronic ganglio-pulmonary lesion of undetermined nature in 16 year old girl;
      possibly sarcoidosis with strictly thoracic involvement].

PMID- 14955606
TI  - [Blood sedimentation rate in bronchogenic cancers].

PMID- 14955607
TI  - [Radiographic pictures of an intra-cardiac gaseous embolism].

PMID- 14955608
TI  - [First symptoms of bronchogenic cancers].

PMID- 14955609
TI  - [Pulmonary calcifications in silicosis].

PMID- 14955610
TI  - [Intra-pulmonary cavities in silicosis visible in tomography].

PMID- 14955611
TI  - [Infiltrative and emphysematous types of Besnier-Boeck-Schaumann disease and
      therapy by cortisone].

PMID- 14955612
TI  - [Non-tubercular intra-pulmonary cavities in silicosis].

PMID- 14955613
TI  - Permeability properties of erythrocyte ghosts.
AB  - 1. Erythrocyte ghosts from human blood were produced by gentle water hemolysis.
      The ghost-containing hemolysate (about 20 mN) was added to media of different
      composition (KCl, NaCl, glucose, sucrose, etc.) and varying concentration ranging
      from 8 to 840 mN. The volume changes of the ghost cells were followed by a light
      absorption method. The potassium and sodium concentrations were also analyzed in
      some representative cases. 2. The ghosts shrank, or swelled, in two stages. An
      initial phase with a momentary expulsion, or uptake, of water leading to an
      osmotic equilibrium, was followed by a second phase in which a slow swelling or
      shrinking proceeded toward a final constant volume. 3. The ghosts were
      semipermeable in the sense that water always passed rapidly in either direction
      so as to maintain isotonicity with the external medium. The relation between
      ghost cell volumes (V) and the total concentration (C(e)) of the suspension
      medium can be expressed by a modified van't Hoff-Mariotte law: (C(e) + a)(V - b)
      = constant. Here a is a term correcting for an internal pressure and b is the non
      solvent volume of the ghost cells. This means that the ghosts behave as perfect
      osmometers. 4. On the other hand appreciable concentration differences of the K
      and Na ions could be maintained across the intact ghost cell membranes for long
      periods. Whether this phenomenon is due simply to very low cation permeability or
      to active transport processes cannot be decided, although the first assumption
      appears more probable. 5. When the ghosts were treated with small concentrations
      of a lytic substance like Na oleate, the alkali ion transfer was greatly
      increased. This seems to be a simple exchange diffusion process with
      simultaneous, continued maintenance of osmotic equilibrium (= the second phase).
      A simplified theory is also given for the kinetics of the volume variations and
      ion exchange during the second phase (cf. the Appendix). 6. Miscellaneous
      observations on the effects of pH, and of some other substances are discussed.
      Some shape transformations of the ghost cells are also described.

PMID- 14955614
TI  - The effect of electrolytes on the contractile elements of muscle.
AB  - The effects of changes in electrolyte concentration on muscles which had been
      preserved in 50 per cent glycerol or washed in water were studied. The psoas
      preparation of Szent-Gyorgyi was generally used, but smooth and cardiac muscle
      gave the same results. If the preparations are immersed in 0.16 molar NaCl or KCl
      and if the electrolyte subsequently is washed out with distilled water, tension
      rises. This effect is not obtained if solutions of CaCl(2) or MgCl(2) are used,
      but it is restored by brief immersion in NaCl or KCl solutions. Changes in pH
      have no effect. It is concluded that divalent cations are bound more firmly than
      monovalent ions, but that divalent exchange with monovalent ions. After the
      application of ATP washing out electrolytes produces a much larger and more rapid
      rise in tension. This effect persists after ATP has been washed out and seems to
      be due to the removal of a substance which diminishes the dissociation of bound
      cations. Washing out electrolytes also causes a large increase in transparency
      and swelling. These effects are also enhanced by previous application of ATP and
      are abolished or diminished by divalent cations. The rise in tension and the
      swelling are explained as the result of an increase in the charge of the polar
      groups of the proteins. Because this mechanism produces only a small degree of
      shortening, it does not explain normal contraction, but it may be a part of this
      process. The significance of the phenomena described in relation to recent
      theories of the mechanism of muscular contraction is discussed. The observations
      show that increase in the charge of the contractile proteins causes contraction,
      not relaxation, as has been commonly assumed.

PMID- 14955615
TI  - Enzymatic dephosphorylation of ovalbumin and plakalbumin.
AB  - It has been shown by the work presented in this paper that it is possible to
      carry out a stepwise dephosphorylation of ovalbumin. With the aid of a prostate
      phosphatase that attacks only one of the two phosphorus-containing groups in the
      major component, A(1), of ovalbumin, a protein, A(2), containing 1 atom of
      phosphorus per mole has been prepared. Further dephosphorylation with an enzyme
      of intestinal origin gives a phosphorus-free ovalbumin, A(3). Plakalbumin has
      been similarly dephosphorylated to give P(2) and P(3). Significant changes in the
      electrophoretic mobility accompany each dephosphorylation step. This, together
      with the phosphorus content of the proteins and the crystal form, has been used
      to characterize and study the five modifications of ovalbumin thus produced.

PMID- 14955616
TI  - The effects of diphtheria toxin on the Cecropia silkworm.
AB  - 1. The metamorphosis of the Cecropia silkworm is accompanied by large and
      systematic changes in the insect's sensitivity to diphtheria toxin. 2. Injection
      of less than 1 gamma of toxin into mature caterpillars, prepupae, or developing
      adults causes cessation of development followed by delayed death 1 to 5 weeks
      later. 3. Dormant pupae, on the contrary, are resistant to 70 gamma of toxin and
      may survive even this enormous dose for over 4 weeks. One-hundredth of this dose,
      however, prevents pupae from initiating adult development. 4. Tetanus toxin, to
      which the insect is insensitive, failed to duplicate any of these effects. 5.
      Maximal sensitivity to diphtheria toxin is characteristic of those stages in the
      life history which depend on the presence and function of the cytochrome system.
      Resistance to the toxin, as in the case of the diapausing pupa, is correlated
      with the existence and utilization of metabolic pathways other than the usual
      cytochrome system. 6. This correlation persists within the individual insect.
      Thus, within the diapausing pupa, the toxin fails to affect the heart in which a
      normal cytochrome system is absent, but, within the same insect, causes a
      degeneration of the intersegmental muscles in which an intact cytochrome system
      is present. 7. These several lines of evidence are interpreted in support of the
      conclusion that diphtheria toxin acts by blocking the synthesis of one or more
      components in the cytochrome system.

PMID- 14955617
TI  - Phage formation in Staphylococcus muscae cultures. XI. The synthesis of
      ribonucleic acid, desoxyribonucleic acid, and protein in uninfected bacteria.
AB  - 1. The synthesis of ribonucleic acid, desoxyribomicleic acid, and protein in S.
      muscae has been studied: (a) during the lag phase, (b) during the early log
      phase, and (c) while the cells are forming an adaptive enzyme for lactose
      utilization. 2. During the lag phase there may be a 60 per cent increase in
      ribonucleic acid and protein and a 50 per cent increase in dry weight without a
      change in cell count, as determined microscopically, or an increase in turbidity.
      3. During this period, the increase in protein closely parallels the increase in
      ribonucleic acid, in contrast to desoxyribonucleic acid, which begins to be
      synthesized about 45 minutes after the protein and ribonucleic acid have begun to
      increase. 4. The RNA N/protein N ratio is proportional to the growth rate of all
      S. muscae strains studied. 5. While the RNA content per cell during the early log
      phase depends upon the growth rate, the DNA content per cell is fairly constant
      irrespective of the growth rate of the cell. 6. Resting cells of S. muscae have
      approximately the same RNA content per cell irrespective of their prospective
      growth rate. 7. While the cells are adapting to lactose, during which time there
      is little or no cellular division, there is never an increase of protein without
      a simultaneous increase in ribonucleic acid, the RNA N/protein N ratio during
      these intervals being approximately 0.15. 8. Lactose-adapting cells show a loss
      of ribonucleic acid. The purines-pyrimidines of the ribonucleic acid can be
      recovered in the cold 5 per cent trichloroacetic acid fraction, but the ribose
      component is completely lost from the system. 9. The significance of these
      results is discussed in relation to the importance of ribonucleic acid for
      protein synthesis.

PMID- 14955618
TI  - An analysis of the inactivation of the frog sperm nucleus by toluidine blue.
AB  - Toluidine blue, applied to frog sperm under appropriate conditions, inactivates
      specifically the sperm nucleus, leaving the extranuclear parts of the cell
      undamaged. Thus, the dye-treated spermatozoa stimulate eggs to cleave normally,
      but contribute no chromosomes to the resulting embryos, which develop as typical
      gynogenetic haploids. The concentration of dye required to produce this
      inactivation varies with pH. Measurements made over the entire pH range which can
      be tolerated by sperm cells showed that in the lower part of the range (5 to 7)
      the effective dye concentration was about 5 x 10(-6)M; in the intermediate range
      (7 to 8.5) it was 1 x (-6) to 1 x (-7)M; and for the higher pH values (8.5 to
      10.0) it was about 5 x (-8)M. Using sperm suspensions containing 1500 cells per
      c. mm. these concentrations of dye produced specific inactivation of the sperm
      nuclei within 7 to 60 minutes at 18 degrees C. Tests of the reversibility of the
      inactivation were made by transferring the sperm from the dye to a dilute
      Ringer's solution after a known degree of inactivation had been produced.
      Following removal of the dye the sperm cells were tested on eggs over a period of
      2 hours. During this time there was no indication of a reversal of the
      inactivation. Microscopic observations of sperm treated with (-5)M or 5 X (-5)M
      dye show that the dye is taken up by the sperm nucleus, which is faintly but
      definitely stained. The dye appears to be uniformly distributed in the nucleus,
      while extranuclear structures remain unstained. Measurements of the amount of dye
      bound per sperm nucleus indicate that the minimal quantity required for complete
      inactivation is about 6.7 x (-18) mole, while the maximal amount which can be
      bound without injury to extranuclear structures is about 1.5 x (-16) mole. The
      value obtained for the minimal requirement (6.7 X (16) mole = 4 X (6) molecules)
      suggests that there are roughly 4 million binding sites in the nucleus which,
      when blocked by dye molecules, somehow prevent the sperm chromosomes from
      participating in the development of the egg.

PMID- 14955619
TI  - Studies on isolated cell components. IV. The effect of various solutions on the
      isolated rat liver nucleus.
AB  - 1. The effects of morganic ions, electrolyte concentration, and pH on the
      appearance and volume of the isolated rat liver nucleus have been studied. Nuclei
      were isolated by differential centrifugation in a buffered salt-sucrose mixture
      at pH 7.1. Nuclear volumes were determined photographically. 2. In solutions of
      NaCl, of KCl, and in potassium phosphate buffers the nuclear volume decreased
      markedly with an increase in concentration from 0.001 M to 0.05 M but remained
      essentially constant with further increase in concentration to 1.0 M. The effects
      of CaCl(2) and MgCl(2) differed from those of NaCl and KCl in that a smaller
      volume was obtained in concentrations less than 0.15 M, and in the case of
      CaCl(2) an increase in volume was obtained in more concentrated solutions. The
      volume changes are considered to be due primarily to ionic effects on the nuclear
      colloids rather than to osmotic behavior. 3. Treatment of nuclei with DNAase
      prevented the characteristic volume changes resulting from ion effects,
      suggesting the importance of DNA in nuclear volume changes. 4. The optical
      changes in isolated nuclei in various concentrations of KCl, NaCl, CaCl(2),
      MgCl(2), and in potassium phosphate buffers as observed under phase contrast
      illumination are described. CaCl(2) gave the most marked nuclear changes from the
      conditions in the uninjured cell and caused shrinkage and granulation in 0.001 M
      concentration. The effects of CaCl(2) were also manifested in 0.88 M sucrose, in
      mixtures with monovalent salts, and in serum. Changes in nuclear volume and
      optical appearance which occurred in salt solutions and in 0.1 N HCl were readily
      reversible. 5. Nuclear volume remained constant between pH 8.91 and 5.12 and
      decreased in more acid solutions. 6. Sucrose had no appreciable osmotic effect,
      and in hyperosmotic solution. (0.88 M) nuclei showed swelling and rupture
      comparable to that in distilled water. 7. The results are considered in relation
      to the requirements of nuclear isolation media. 8. Rat liver nuclei isolated in a
      buffered salt-sucrose medium by differential centrifugation exhibited a pattern
      of size distribution similar to that of fixed nuclei but were of considerably
      larger volume. The ratio of the volumes of the peak frequencies of the two chief
      size groups was 1:1.9.

PMID- 14955620
TI  - The role of sulfhydryl groups in the bleaching and synthesis of rhodopsin.
AB  - The condensation of retinene(1) with opsin to form rhodopsin is optimal at pH
      about 6, a pH which favors the condensation of retinene(1) with sulfhydryl rather
      than with amino groups. The synthesis of rhodopsin, though unaffected by the less
      powerful sulfhydryl reagents, monoiodoacetic acid and its amide, is inhibited
      completely by p-chloromercuribenzoate (PCMB). This inhibition is reversed in part
      by the addition of glutathione. PCMB does not attack rhodopsin itself, nor does
      it react with retinene(1). Its action in this system is confined to the -SH
      groups of opsin. Under some conditions the synthesis of rhodopsin is aided by the
      presence of such a sulfhydryl compound as glutathione, which helps to keep the 
      SH groups of opsin free and reduced. By means of the amperometric silver
      titration of Kolthoff and Harris, it is shown that sulfhydryl groups are
      liberated in the bleaching of rhodopsin, two such groups for each retinene(1)
      molecule that appears. This is true equally of rhodopsin from the retinas of
      cattle, frogs) and squid. The exposure of new sulfhydryl groups adds an important
      element to the growing evidence that relates the bleaching of rhodopsin to
      protein denaturation. The place of sulfhydryl groups in the structure of
      rhodopsin is still uncertain. They may be concerned directly in binding the
      chromophore to opsin; or alternatively they may furnish hydrogen atoms for some
      reductive change by which the chromophore is formed from retinene(1). In the
      amperometric silver titration, the bleaching of rhodopsin yields directly an
      electrical variation. This phenomenon may have some fundamental connection with
      the role of rhodopsin in visual excitation, and may provide a model of the
      excitation process in general.

PMID- 14955621
TI  - [Therapy of hydatid cysts of the lungs and their complications].

PMID- 14955622
TI  - [Pathology and therapy of gallbladder diseases].

PMID- 14955623
TI  - [Surgery of arthritis and arthroses].

PMID- 14955624
TI  - [Account on melorheostosis].

PMID- 14955625
TI  - Anastomosis of the rectum without suture; a preliminary report.

PMID- 14955626
TI  - Renal metastasis in carcinoma of the pancreas.

PMID- 14955627
TI  - Treatment of bursitis by local injection of hydrocortisone acetate.

PMID- 14955628
TI  - Therapeutic pituitary inhibition by steroids; treatment of exophthalmos.

PMID- 14955629
TI  - Surgical correction of prognathism.

PMID- 14955630
TI  - Cosmetic surgery of the nose in Israel.

PMID- 14955631
TI  - Partial resection of the anterior thoracic wall with skin flap reconstruction.

PMID- 14955632
TI  - Tuberculosis of the ileocecal area.

PMID- 14955633
TI  - Phthalyl sulfathiazole in the treatment of experimental peritonitis in rats.

PMID- 14955634
TI  - Intestinal obstruction due to gallstone impaction.

PMID- 14955635
TI  - Surgical treatment of the undescended testis.

PMID- 14955636
TI  - The gastric cripple after total gastric resection.

PMID- 14955637
TI  - WIDENING circle.

PMID- 14955638
TI  - INTERNATIONAL College of Surgeons.

PMID- 14955639
TI  - A local defect in the metabolism of pyridoxine in the skin of person with
      seborrheic dermatitis of the "sicca" type.

PMID- 14955640
TI  - Ineffectiveness of local applications of adrenocortical steroids in preventing
      effects of ultraviolet rays on human skin.

PMID- 14955641
TI  - The effect of topically applied compound F in selected dermatoses.

PMID- 14955642
TI  - A modified Van Tieghem mount.

PMID- 14955643
TI  - Experiments on the choline content of the skin and sebum.

PMID- 14955644
TI  - The effect of intradermal injection of adreno-cortical hormones.

PMID- 14955645
TI  - Histopathology of nail diseases.

PMID- 14955646
TI  - Physiology of the glands of the human ear canal: preliminary report.

PMID- 14955647
TI  - The insect bite reaction. II. Evaluation of the allergic reaction.

PMID- 14955648
TI  - Use of a quartz fiber microbalance for histochemical investigations of skin.

PMID- 14955649
TI  - Esterification of serum cholesterol. I. Serial determinations in health.

PMID- 14955650
TI  - Esterification of serum cholesterol. II. Influence of phosphatide and other
      factors.

PMID- 14955651
TI  - Esterification of serum cholesterol. III. In hypercholesterolemic rabbits.

PMID- 14955652
TI  - Femoral arteriovenous sugar differences in fasting human beings.

PMID- 14955653
TI  - Radiation reactions in parabiotic rats.

PMID- 14955654
TI  - The protective effect of shielded ectopic bone marrow against total body x
      radiation.

PMID- 14955655
TI  - Plasma antithrombin in thrombosis, hemorrhage, and liver disease.

PMID- 14955656
TI  - Pathogenesis of the plasma transfusion reaction with especial reference to the
      blood coagulation system.

PMID- 14955657
TI  - Cardiopulmonary studies in patients with mitral stenosis. I. Cardiovascular
      dynamics.

PMID- 14955658
TI  - Pancreatitis in methyl alcohol poisoning.

PMID- 14955659
TI  - Bronchospirometry. IV. Ambient-air and oxygen-recording bronchospirometry.

PMID- 14955660
TI  - Spectrophotometric determination of oxyhemoglobin saturation and oxygen content
      of blood.

PMID- 14955661
TI  - Use of an artificial kidney. III. Current procedures in clinical hemodialysis.

PMID- 14955662
TI  - Use of the whole blood oximeter during cardiac catheterization.

PMID- 14955663
TI  - The conversion of Millikan and Wood type oximeters into direct-writing recording
      instruments for use in surgery, in studies of pulmonary function, and in teaching
      respiratory physiology.

PMID- 14955664
TI  - A diluting fluid for counting erythrocytes which simultaneously stains the cells
      and makes them lie flat within a single focal plane.

PMID- 14955665
TI  - A neurosurgical and multiple purpose monkey chair.

PMID- 14955666
TI  - Apparatus for tube-feeding rats.

PMID- 14955667
TI  - Laryngeal nodes and the so-called amyloid tumour of the cords.

PMID- 14955668
TI  - Rhinitis caseosa.

PMID- 14955669
TI  - A determination of the normal threshold of hearing and its relation to the
      standardization of audiometers.

PMID- 14955671
TI  - A critical analysis of the ears of a thousand normal young men.

PMID- 14955670
TI  - The determination of the threshold of hearing.

PMID- 14955672
TI  - Three cases of infected laryngocele.

PMID- 14955673
TI  - A case of gross hyperplasia of the tonsils in a man aged 77.

PMID- 14955674
TI  - PURE tone audiometry; technique for determining thresholds of hearing for pure
      tones.

PMID- 14955675
TI  - [Evolution of the clinical trend and hospital orientation].

PMID- 14955676
TI  - [Infarction of the left colon].

PMID- 14955677
TI  - [Rectal sequelae after curietherapy for cancer of the cervix uteri].

PMID- 14955678
TI  - [Eleven cases of testicular cancer].

PMID- 14955679
TI  - [Tracheobronchial restorative surgery].

PMID- 14955680
TI  - [Trichloroethylene].

PMID- 14955681
TI  - [The great hazard of iso-immunization caused by careless transfusions].

PMID- 14955682
TI  - [Medical treatment of gastro-duodenal ulcer].

PMID- 14955683
TI  - [Compulsory vaccination for travel abroad and in the French Union].

PMID- 14955684
TI  - [Primary infection with inguinal manifestations simulating Nicolas-Favre
      disease].

PMID- 14955685
TI  - [The physiopathology and treatment of intestinal obstruction].

PMID- 14955686
TI  - Observations on partial removal of the post-central gyrus for pain.

PMID- 14955687
TI  - Micturition reflexes in man.

PMID- 14955688
TI  - Thermal sensation in the bladder.

PMID- 14955689
TI  - Two cases of Aspergillus infection of the central nervous system.

PMID- 14955690
TI  - The localization of aneurin pyrophosphatase in the brain.

PMID- 14955691
TI  - Wounds of the visual pathway. Part II. The striate cortex.

PMID- 14955692
TI  - Dysphasia in left-handed patients with unilateral brain lesions.

PMID- 14955693
TI  - Cerebral dominance in cases of reading disability.

PMID- 14955695
TI  - Observations on a case of myotonia paradoxa.

PMID- 14955694
TI  - Electromyographic and endocrine studies in chronic thyrotoxic myopathy.

PMID- 14955696
TI  - The vital staining of muscle biopsies with methylene blue.

PMID- 14955697
TI  - Potential changes in spinal cord following administration of strychnine.

PMID- 14955698
TI  - Reflexes to stretch and contraction of antagonists around ankle joint.

PMID- 14955699
TI  - Electrical activity of single units in cervical cord.

PMID- 14955700
TI  - Exteroceptive abdominal reflexes in dogs.

PMID- 14955701
TI  - Descending spinal pathways mediating pressor responses of cerebral origin.

PMID- 14955702
TI  - On a "sympathetic" component in the afferent innervation of trunk dermatomes.

PMID- 14955703
TI  - Threshold movements produced by excitation of cerebral cortex and efferent fibers
      with some parametric regions of rectangular current pulses (cats and monkeys).

PMID- 14955704
TI  - Free amino acids in chick livers as altered by vitamin B12 and fasting.

PMID- 14955705
TI  - Amino acids in the production of blood constituents in rats.

PMID- 14955706
TI  - The effects of iodinated casein, thiouracil and cortisone on the ascorbic acid
      requirement of the male guinea pig.

PMID- 14955707
TI  - The ascorbic acid requirement of the guinea pig when adrenal weight and
      odontoblast height are used as criteria.

PMID- 14955708
TI  - The urinary excretion of vitamin B12 following subcutaneous administration to
      young and adult rats with different reserves.

PMID- 14955709
TI  - The biological activity of diethyl riboflavin.

PMID- 14955710
TI  - The excretion of injected P32 into the gastrointestinal tract of the young calf.

PMID- 14955711
TI  - The metabolic fecal phosphorus excretion of the young calf.

PMID- 14955712
TI  - Tri-o-cresyl phosphate as a vitamin E antagonist for the rat and lamb.

PMID- 14955713
TI  - Comparison of methods for determination of the vitamin B12 potency of meats.

PMID- 14955714
TI  - Deposition of fluorine in the bones and teeth of the growing rat.

PMID- 14955715
TI  - Reproduction studies with dogs. I. Effect of a corn-soybean meal-alfalfa diet.

PMID- 14955716
TI  - The requirement for isoleucine and the activities of its isomers for the growth
      of turkey poults.

PMID- 14955717
TI  - Masculinization associated with luteinized microcysts of the ovary.

PMID- 14955718
TI  - Foetal and infant mortality in multiple pregnancy.

PMID- 14955719
TI  - The incidence of foetal and infant mortality in 13,085 births in a maternity
      hospital; an inquiry into the influence of non-obstetric factors on the
      difference between the booked and the non-booked foetal and infant mortality.

PMID- 14955720
TI  - Signet-ring celled carcinoma of the ovary (Krukenberg tumour).

PMID- 14955721
TI  - An inquiry into the treatment of postpartum haemorrhage.

PMID- 14955722
TI  - Reticuloendothelial cells in the uterine horns of the guinea-pig; an endometrial
      cycle independent of the ovaries.

PMID- 14955723
TI  - Pregnancy and labour in the young mother.

PMID- 14955724
TI  - Twin pregnancy; a review of 472 cases.

PMID- 14955725
TI  - Angular pregnancy.

PMID- 14955726
TI  - Massive haemorrhage following anti-coagulant therapy in pregnancy.

PMID- 14955727
TI  - Intestinal diverticulitis and the gynaecologists.

PMID- 14955728
TI  - A triplet pregnancy complicated by thyroidectomy, pyelitis and anaemia followed
      by menorrhagia.

PMID- 14955729
TI  - Unusual pressure effect of a fibroid.

PMID- 14955730
TI  - Fluid record chart.

PMID- 14955731
TI  - An unusual sub-mucous uterine fibroid.

PMID- 14955732
TI  - Recent developments in the clinical application of hormone assay.

PMID- 14955733
TI  - Four cases of recurrent placenta praevia.

PMID- 14955734
TI  - Two cases of pregnancy in association with malignant ovarian tumours.

PMID- 14955735
TI  - Cardiac disease in pregnancy.

PMID- 14955736
TI  - Cephalhematoma associated with fracture of the skull.

PMID- 14955737
TI  - Hemorrhagic infarction of the kidneys in infants: report of a unilateral case in
      an 8-day-old male infant with survival of infant following successful
      nephrectomy.

PMID- 14955738
TI  - Endocardial fibroelastosis: case reports with special emphasis on the clinical
      findings.

PMID- 14955739
TI  - A study of the hypnotic effect of dormison in children.

PMID- 14955740
TI  - Impetigo and acute infectious exfoliative dermatitis of the newborn infant
      (Ritter's disease).

PMID- 14955741
TI  - Molybdenized ferrous sulfate (mol-iron) in the treatment of the anemia of
      premature infants.

PMID- 14955742
TI  - Polymyxin B in pseudomonas and proteus enteritis.

PMID- 14955743
TI  - Treatment of acute infantile diarrhea with carob flour (arobon).

PMID- 14955744
TI  - Generalized cutaneous herpes simplex; report of a case complicating
      meningococcemia.

PMID- 14955745
TI  - Congenital hypertrophic pyloric stenosis in a small premature infant.

PMID- 14955746
TI  - Duplication of the alimentary tract.

PMID- 14955747
TI  - Hypervitaminosis A.

PMID- 14955748
TI  - Chemical growth in infancy and childhood.

PMID- 14955749
TI  - Everyday problems of the preschool child.

PMID- 14955750
TI  - The newer tests for polio.

PMID- 14955751
TI  - Poliomyelitis and immunization.

PMID- 14955752
TI  - [New barbituric acid derivatives with narcotic and anesthetic effects].

PMID- 14955753
TI  - [Citrinin].

PMID- 14955754
TI  - [Notes on the trial therapeutic use of citrinin].

PMID- 14955755
TI  - [Spectrophotometric study of strychnine and of brucine].

PMID- 14955756
TI  - [Notes on the application of the potentiometric method in the titration of
      papaverine and of phenylethylbarbituric acid in certain complex preparations].

PMID- 14955757
TI  - [Determination of zinc oxide in ointments].

PMID- 14955758
TI  - [Contribution to the analytical study of 3,3-diethyl-2,4
      diketotetrahydropyridine].

PMID- 14955759
TI  - [Instantaneous control of the identity and purity of drugs and organic
      compounds].

PMID- 14955760
TI  - [Physical and chemical methods in the analysis of cardiotonic glycosides].

PMID- 14955761
TI  - [Note on the determination of arsenic in sodium nitrite].

PMID- 14955763
TI  - [Some pharmacodynamic properties of bis-(2-heptyl) amine].

PMID- 14955762
TI  - [Experimental contribution to the study of rheumatic diseases].

PMID- 14955764
TI  - [Variation in the content of the active principle in certain medicinal capsules].

PMID- 14955765
TI  - [Determination of monobromoacetic acid in milk].

PMID- 14955766
TI  - [Separation of mixtures of the vitamins of the B group by chromatography and
      ultraviolet spectrophotometry].

PMID- 14955767
TI  - The influence of enzyme inhibitors on the action of epinephrine on the frog's
      heart.

PMID- 14955768
TI  - Mode of action of antagonists to curare.

PMID- 14955769
TI  - Depression of transmission through sympathetic ganglia during general anesthesia.

PMID- 14955770
TI  - Bioassay of Veratrum viride. I. Effect of vergitryl on carotid sinus pressor
      reflex.

PMID- 14955771
TI  - The role of body fat in limiting the duration of action of thiopental.

PMID- 14955772
TI  - The role of the liver in the metabolic disposition of isopropyl alcohol.

PMID- 14955773
TI  - Nature of the hypotensive action of a thiophanium derivative (Ro 2-2222) in dogs.

PMID- 14955774
TI  - The effects of progesterone and some related steroids on the contraction of
      isolated myocardium.

PMID- 14955775
TI  - Central depressant and anticonvulsant properties of glycerol ethers isomeric with
      mephenesin.

PMID- 14955776
TI  - Actions and addiction liabilities of alpha-acetyl-methadols in man.

PMID- 14955777
TI  - Effects of regitine (C-7337) upon the blood flow responses to epinephrine in the
      innervated hind limb of the dog.

PMID- 14955778
TI  - Effect of cardiac glycoside on the contraction and the energy-rich phosphate
      content of the heart poisoned with dinitrophenol.

PMID- 14955779
TI  - Pharmacological properties of benzazoles. I. Relationship between structure and
      paralyzing action.

PMID- 14955780
TI  - Comparative effects of 20 mgm. of morphine sulfate on non-addicts and former
      morphine addicts.

PMID- 14955781
TI  - Effect of non-opiate analgesics and other drugs on the vibratory threshold.

PMID- 14955782
TI  - Effects of a new dibenzazephine derivative, RO 2-3248, 6-allyl-6, 7-dihydro-5H
      dibenz [c,e] azepine phosphate, upon the blood flow, the peripheral resistance
      and the response to injections of epinephrine of the innervated hind limb of the
      dog.

PMID- 14955783
TI  - Failure to find a reversal by BAL of the pentobarbital inhibition of brain
      metabolism.

PMID- 14955784
TI  - Effect of nitrogen mustard in alloxan diabetes.

PMID- 14955785
TI  - Effect of 1-cyclohexylamino-2-propylbenzoate (cyclaine) and other local
      anesthetic agents administered intravenously on the cardiovascular respiratory
      systems of the dog.

PMID- 14955786
TI  - Laboratory and clinical observations on the effect of regitine (C-7337) on
      cardiac irregularities during cyclopropane anesthesia.

PMID- 14955787
TI  - Effect of cocaine on cardiac automaticity in the dog.

PMID- 14955788
TI  - A comparative study of the effects of 1-arterenol, epinephrine and
      isopropylarterenol on the heart.

PMID- 14955789
TI  - The determination of d-amphetamine in body fluids.

PMID- 14955790
TI  - A clinical study of prolonged anticoagulant effect with repository butacaine
      heparin.

PMID- 14955791
TI  - Creatine synthesis by rat liver, in vitro, as influenced by carbon tetrachloride
      and dietary vitamin E.

PMID- 14955792
TI  - Cassaine and cassaidine: quantitative measurements of heart contractile force in
      situ.

PMID- 14955793
TI  - On the mechanism of the antidiuretic action of cinchoninic acid derivatives.

PMID- 14955794
TI  - The antidiuretic action of epinephrine and norepinephrine.

PMID- 14955795
TI  - Instruments employed in potentiometric determinations.

PMID- 14955796
TI  - Studies in the effect of substitution on the local anaesthetic activity of
      pyrazoline derivatives. Part I. 1-Phenyl-5(3'methoxy-4'-n-propoxyphenyl)-3-beta
      dialkylamino (piperidino; morpholino)-pyrazolines.

PMID- 14955797
TI  - Brazilian jalap. Part III. An examination of the resin and some comparisons with
      the resins from Vera Cruz jalap and Orizaba jalap.

PMID- 14955798
TI  - A colour reaction for certain mercaptoimidazoles using iodobismuthous acid.

PMID- 14955799
TI  - The bacteriostatic action of basic di- and triphenylmethane derivatives. Part II.
      The relations between chemical structure and bacteriostatic effects.

PMID- 14955800
TI  - The official limit test for chloride in bromides.

PMID- 14955801
TI  - The thiocyanate titration of mercury and the standardization of ammonium
      thiocyanate solution.

PMID- 14955802
TI  - The determination of iodine in organic compounds by alkaline reduction.

PMID- 14955803
TI  - The stability and preservation of litmus solutions.

PMID- 14955804
TI  - The determination of the acid value of benzoin.

PMID- 14955805
TI  - Action currents in single afferent nerve fibres elicited by stimulation of the
      skin of the toad and the cat.

PMID- 14955806
TI  - Analysis of afferent and efferent systems in the muscle nerve of the toad and
      cat.

PMID- 14955807
TI  - The effect of injection of hypertonic salt solution on the chloride content of
      mammalian skin.

PMID- 14955808
TI  - Action potentials of isolated mammalian sympathetic ganglia.

PMID- 14955809
TI  - Responses of isolated curarized sympathetic ganglia.

PMID- 14955810
TI  - The effect of acute reduction of the glomerular filtration rate on sodium
      excretion in man.

PMID- 14955811
TI  - An electromyographic study of the role of the abdominal muscles in breathing.

PMID- 14955812
TI  - The level of free choline in plasma.

PMID- 14955813
TI  - Effect of choline on neuromuscular transmission in the cat.

PMID- 14955814
TI  - Repeatable micro-shocks of constant strength in guinea-pig anaphylaxis.

PMID- 14955815
TI  - A method of investigating the effects of close arterial injections on spinal cord
      activity.

PMID- 14955816
TI  - Histamine recovery in the rat's and dog's skin.

PMID- 14955817
TI  - Histamine release from skin by horse serum.

PMID- 14955818
TI  - Pain-producing substances in blister fluid and in serum.

PMID- 14955819
TI  - Reflex interaction of synergic extensor muscles of the cat hind limb.

PMID- 14955820
TI  - Penetration of 32p and 24Na into nervous tissues of the rabbit.

PMID- 14955821
TI  - Synaptic excitation and inhibition.

PMID- 14955822
TI  - The utilization of 14C-labelled amino-acids by the isolated mammalian heart.

PMID- 14955823
TI  - Changes in the flow of lymph and in the secretion of urine due to the carotid
      sinus reflex.

PMID- 14955824
TI  - The blood supply of the carotid body.

PMID- 14955825
TI  - On the increase in muscle blood flow following contraction.

PMID- 14955826
TI  - [The informative role of art in psychology].

PMID- 14955827
TI  - [Differentiation between speech and language].

PMID- 14955828
TI  - [The jargon of aphasics; anosognosic disintegration of semantic values of
      language].

PMID- 14955829
TI  - [Legal evidence].

PMID- 14955830
TI  - [Psycho-sociological conditioning: technical and natural environment].

PMID- 14955831
TI  - [Twin situation and mental development].

PMID- 14955832
TI  - [Seventh International on the History of Religions].

PMID- 14955833
TI  - Exercise medical mushroom; D.G.A.M.S. annual exercise, 1951.

PMID- 14955834
TI  - Health education in the army; a factual summary.

PMID- 14955835
TI  - Streptococcal tonsillitis; an explosive epidemic.

PMID- 14955836
TI  - The transmutation of energy and matter.

PMID- 14955837
TI  - Rapid treatment of mass casualties.

PMID- 14955838
TI  - Self-induced lateral pharyngeal diverticula.

PMID- 14955839
TI  - [Diabetes mellitus in post-operative hypothyroidism following hyperthyroidism;
      role for the pituitary gland].

PMID- 14955840
TI  - [Narcotics and freedom of prescription].

PMID- 14955841
TI  - [Test of renal clearance of combined thiosulfate of sodium and paraaminohippuric
      acid].

PMID- 14955842
TI  - [The Rana reaction in pathological pregnancy].

PMID- 14955843
TI  - [Sensitivity of Rana esculenta to gonadotrophic hormones].

PMID- 14955844
TI  - [The frog-unit of gonadotrophic hormones].

PMID- 14955845
TI  - [The Rana reaction in a case of testicular tumor].

PMID- 14955846
TI  - [Histio-leukemia (malignant reticulosis) in a child aged two and one-half
      months].

PMID- 14955847
TI  - [Recent data on antigen-reagents used for serodiagnosis of syphilis;
      cardiolipin].

PMID- 14955848
TI  - [Experimentation and pathogenesis of the arterial hypertension essay of
      synthesis].

PMID- 14955849
TI  - [Trial of external usage of chloramphenicol in otorhinology].

PMID- 14955850
TI  - [Extrapyramidal syndromes caused by carbon monoxide poisoning].

PMID- 14955851
TI  - [Leukoses and bone diseases].

PMID- 14955852
TI  - [Hypothyroidism; thyroid treatment with improvement followed by angor and death
      caused by obliterating coronaritis and infarct].

PMID- 14955853
TI  - [Hydatiform mole and its effect on fecundity (statistics on 50 cases)].

PMID- 14955854
TI  - [A case of cancer of the ampulla of Vater and multiple cancer].

PMID- 14955855
TI  - [Respiratory function in silicotics].

PMID- 14955856
TI  - [Professor Andre Le Grand (1895-1951), teacher and friend].

PMID- 14955857
TI  - [Funeral of Professor Andre Le Grand].

PMID- 14955858
TI  - [Andre Le Grand, physiologist].

PMID- 14955859
TI  - [Works of Professor Andre Le Grand].

PMID- 14955860
TI  - [Some points on anatomy of the ureter and their practical significance].

PMID- 14955861
TI  - [Cochleo vestibular disorders and cervical arthrosis; 40 cases].

PMID- 14955862
TI  - [Horseshoe kidneys; importance of retropneumoperitoneum].

PMID- 14955863
TI  - [Second European Congress of the International Association for bronchial
      studies].

PMID- 14955864
TI  - [General therapeutic directions in chronic progressive inflammatory rheumatism:
      hormone therapy with cortisone, ACTH and gold salts].

PMID- 14955865
TI  - [Social and economic results of gastrectomy in coal miners].

PMID- 14955866
TI  - [Rheumatology Week at Aix-les-Bains-May 1952].

PMID- 14955867
TI  - Diagnosis and treatment of pheochromocytoma.

PMID- 14955868
TI  - Intrarenal gas: report of case and review of literature.

PMID- 14955869
TI  - Renal papillary necrosis: case report.

PMID- 14955870
TI  - Infected cyst of the kidney.

PMID- 14955871
TI  - Echinococcus disease of the kidney.

PMID- 14955872
TI  - Bilateral ureteral obstruction due to compression by chronic retroperitoneal
      inflammation.

PMID- 14955874
TI  - Vesico-ureteral reflux in the paraplegic: cause and correction.

PMID- 14955873
TI  - Periureteral and peripelvic (renal), extension of carcinoma of cervix: case
      report.

PMID- 14955875
TI  - Leiomyosarcoma in diverticulum of the bladder.

PMID- 14955876
TI  - Podophyllin in treatment of human adenocarcinoma of bladder.

PMID- 14955877
TI  - Treatment of epispadias: a report of 18 cases.

PMID- 14955878
TI  - Urethral rupture: early and late posterior complications.

PMID- 14955879
TI  - Urethral stricture: a study of 227 cases.

PMID- 14955880
TI  - Co-existence of congenital median bar and urethral valves.

PMID- 14955881
TI  - Treatment of carcinoma of the prostate by interstitial radiation with radio
      active gold (Au 198): a preliminary report.

PMID- 14955882
TI  - Radical retropubic prostatectomy for tuberculosis.

PMID- 14955883
TI  - Obturator crush for osteitis pubis.

PMID- 14955884
TI  - Carcinoma of the scrotum: new approach to inguinal gland dissection.

PMID- 14955885
TI  - The potentiality of the peritoneum as a dialyzine membrane.

PMID- 14955886
TI  - Two kinds of culture methods for early detection of tubercle bacilli. II.
      Centrifuge tube culture method.

PMID- 14955887
TI  - On the relations of sites of inoculation and local lesions to the degree of
      immunity in case of BCG vaccination in guinea pigs.

PMID- 14955888
TI  - Studies on the homogeneous culture of tubercle bacilli and BCG strain. II. On the
      properties and homogeneity of organisms grown by the shaking culture method in
      serum-Kirchners media added with paraffin oil.

PMID- 14955889
TI  - On the appearance of streptomycin resistant strains in the sputa of various types
      of pulmonary tuberculosis patients treated with streptomycin.

PMID- 14955890
TI  - Effect of chemotherapeutic preparations on the protective functions of living
      bodies, especially that of anti-tuberculosis preparations. I. Effect on the
      function of erythrocyte.

PMID- 14955891
TI  - On absorption and excretion of TB 1-698.

PMID- 14955892
TI  - The lipase content of the serum of rabbits inoculated with living or killed
      tubercle bacilli.

PMID- 14955893
TI  - CLINICAL and experimental studies on the precipitation reactions of the sera
      obtained from tuberculosis patients against the antigens prepared from tubercle
      bacillus and timothy bacillus. I. On the precipitation reactions of the sera
      obtained from tuberculosis patients against the antigens prepared from tubercle
      bacillus and timothy bacillus.

PMID- 14955894
TI  - Studies on comparison of of old tuberculin and o-aminophenol-azo-tuberculin. I.
      Comparison of Aoyama B old tuberculin with Aoyama B azo-tuberculin and BCG azo
      tuberculin by the intradermal reactions produced in animals.

PMID- 14955895
TI  - [Soor infection and therapy with antibiotics].

PMID- 14955896
TI  - [Arthromyodysplasia congenita].

PMID- 14955897
TI  - [Volvulus of the stomach of fetal genesis, resembling pylorospasm].

PMID- 14955898
TI  - [Transportation of newborn; description of a simple apparatus].

PMID- 14955899
TI  - [From the foundling home to the pediatric hospital].

PMID- 14955900
TI  - [Concomitant rib shadows in thoracic rickets].

PMID- 14955901
TI  - [From the Swiss pediatric literature of 1948 and 1949].

PMID- 14955902
TI  - [Primary elephantiasis; report of two cases].

PMID- 14955904
TI  - [Supervision and medical therapy of congenital cardiovascular defects in
      children].

PMID- 14955903
TI  - [Relation of spinal fluid and blood sugar in the normal child].

PMID- 14955905
TI  - [Central neurofibromatosis].

PMID- 14955906
TI  - [Erythroderma desquamative Leiner].

PMID- 14955907
TI  - [Therapeutic use of hyaluronidase in pediatrics].

PMID- 14955908
TI  - [Errors in preparation for pyelography].

PMID- 14955909
TI  - [The American pediatric literature of the year 1950].

PMID- 14955910
TI  - [The French pediatric literature of 1949-1950].

PMID- 14955911
TI  - [Prof. Dr. J. Ibrahim -- 75th birthday].

PMID- 14955912
TI  - [Clinical use and effects of trichlorethylene in children].

PMID- 14955913
TI  - [Severe burns in childhood].

PMID- 14955914
TI  - [Reliability of tests indicating addition of cows milk to human milk].

PMID- 14955915
TI  - [Enterocystoma of the Ileum causing invaginato ileo-coecalis].

PMID- 14955916
TI  - [Experiences with corella infant milk].

PMID- 14955917
TI  - [Simplification of the Coombs test in the clinical laboratory].

PMID- 14955918
TI  - [Value of cardiac murmurs in diagnosis of heart disease in children].

PMID- 14955919
TI  - [Formulas with increased amount of fat].

PMID- 14955920
TI  - [French pediatric literature in the years 1949-1950].

PMID- 14955921
TI  - [A few important papers of the nordic pediatric literature in the years 1948
      1949].

PMID- 14955922
TI  - [Clinical Evening at the Empress-Auguste Victoria- Haus in Berlin, October 24,
      1951].

PMID- 14955924
TI  - [Acute exophthalmic goiter].

PMID- 14955923
TI  - [First results of activities of the therapeutic clinic in the region of Kuibyshev
      hydroelectric station].

PMID- 14955925
TI  - [Clinical aspects of neuroses in internal diseases].

PMID- 14955926
TI  - [Clinical aspect of infectious thrombosis of the cavernous sinus].

PMID- 14955927
TI  - [Treatment of nocturnal enuresis by conditioned reflex].

PMID- 14955928
TI  - [Problem of the mechanism of erythrocytes sedimentation].

PMID- 14955929
TI  - [Repeated blood transfusion following cancer surgery].

PMID- 14955930
TI  - [Thrombocyte content in peripheral blood in various duodenal and bile ducts
      diseases and effect on thrombocytopoiesis of the duodenal juice taken from
      patients with biliary and duodenal diseases].

PMID- 14955932
TI  - [Method of blood transfusion and administration of medicinal substances into
      porous bones].

PMID- 14955931
TI  - [Blood transfusion in thoracic surgery].

PMID- 14955933
TI  - [Effect of aerosol penicillin therapy on changes of micro-flora in the sputum].

PMID- 14955934
TI  - [Restoration of vital functions of the organism following fatal electric shock].

PMID- 14955935
TI  - [Certain cardiovascular function tests in chronic coronary insufficiency].

PMID- 14955936
TI  - [Perfil'ev's method of blood staining].

PMID- 14955937
TI  - [Xanthomatosis of the bone with hypertensive manifestations].

PMID- 14955939
TI  - [Case of biliobronchial fistula].

PMID- 14955938
TI  - [Diagnosis of thrombosis of the pulmonary artery during life].

PMID- 14955940
TI  - [Effect of vitamin C and calcium chloride on blood pressure dynamics and
      capillary fragility in hypertension].

PMID- 14955941
TI  - [Fluorescein test of capillary permeability and relation of its dynamics to
      organic vitamin C].

PMID- 14955942
TI  - [Effect of certain drugs on the content of ascorbic acid in the blood].

PMID- 14955943
TI  - [Liver function in hypertension].

PMID- 14955944
TI  - [Roentgenocardiokymography in Basedow's disease].

PMID- 14955945
TI  - [Changes of the bone marrow in hemorrhagic nephroso-nephritis].

PMID- 14955946
TI  - [Discovery of the Shumlianskii's capsule].

PMID- 14955947
TI  - [A new method to protect the lens in deep ceratoplastic surgery].

PMID- 14955948
TI  - [Repeated ceratoplasty].

PMID- 14955949
TI  - [Surgical risk in hypertensive patients].

PMID- 14955950
TI  - [Conservative therapy of the cataract].

PMID- 14955951
TI  - [Choice of surgical method in strabismus divergens].

PMID- 14955952
TI  - [Experiences with simultaneous amount of anteposition and postposition according
      to Kunz's method].

PMID- 14955953
TI  - [Therapy of the absolute glaucoma with mydriatics for anesthetic purposes].

PMID- 14955955
TI  - [Absorption of fluoresceine into the anterior chamber].

PMID- 14955954
TI  - [Functional tests in primary glaucoma to diagnose functional disturbances;
      statistical and analytical evaluation of the function tests].

PMID- 14955956
TI  - [Dark adaptation in glaucoma].

PMID- 14955957
TI  - [Accommodation in vision thru the glasses for close objects].

PMID- 14955958
TI  - [Tape-like degeneration of the cornea, iritis and complete cataract, three
      symptoms caused by polyarthritis chronica infantilis (Still's syndrome)].

PMID- 14955959
TI  - [Bilateral atrophy of the optic nerve caused by acute thallium poisoning].

PMID- 14955960
TI  - [Mechanical factors in genesis of myopia].

PMID- 14955962
TI  - [Detection of simulation of total blindness by optokinetic tests].

PMID- 14955961
TI  - [Accommodative shift of the nucleus of the lens in intracapsular accommodation].

PMID- 14955963
TI  - [Mecklenburg Regional Ophthalmology Society].

PMID- 14955964
TI  - [Meeting of the Ophthalmology Society at the University of Leipzig, a Dresden
      subsidiary].

PMID- 14955965
TI  - [Ophthalmology Society at the University of Berlin].

PMID- 14955966
TI  - Epidemic hemorrhagic fever of the Far East or endemic hemorrhagic nephroso
      nephritis; morphology and pathogenesis.

PMID- 14955967
TI  - Liver damage in rats from radioactive colloidal gold.

PMID- 14955968
TI  - Influence of the site of experimental biliary obstruction upon functional and
      morphologic hepatic injury.

PMID- 14955969
TI  - Effects of cortisone and ACTH on plasma protein electrophoretic patterns.

PMID- 14955970
TI  - A study of glia by the Golgi method.

PMID- 14955971
TI  - Pathologic changes after bilateral nephrectomy in dogs and rats.

PMID- 14955972
TI  - A method for the identification of lipiodol in tissue sections.

PMID- 14955973
TI  - A comparison of perforated cellophane and plasma clot slide technics for
      culturing human tumors.

PMID- 14955974
TI  - Preservation of uric acid infarcts in the museum.

PMID- 14955975
TI  - Use of the polyethylene glycols in dry preservation of anatomic and pathologic
      specimens.

PMID- 14955976
TI  - Marfan's syndrome; observations at necropsy: with special reference to
      medionecrosis of the great vessels.

PMID- 14955977
TI  - Immunity to viruses a general discussion with special reference to the role of
      allergy.

PMID- 14955978
TI  - Exact determination of the central venous pressure by a simple clinical method.

PMID- 14955979
TI  - Diagnosis of mixed parotid tumours.

PMID- 14955980
TI  - Serum-antithrombin level in fibrocystic disease of the pancreas.

PMID- 14955981
TI  - Local use of antibiotics in chronic suppuration of the middle ear and mastoid,
      with particular reference to terramycin.

PMID- 14955982
TI  - The site of action of the toxin in local tetanus.

PMID- 14955983
TI  - Polyarteritis nodosa after thiouracil.

PMID- 14955984
TI  - Petrol pneumonia.

PMID- 14955985
TI  - Mepacrine and rheumatoid arthritis.

PMID- 14955986
TI  - INFANTILE gastro-enteritis.

PMID- 14955987
TI  - NEUROLOGY advances.

PMID- 14955988
TI  - CRIMINAL statistics.

PMID- 14955989
TI  - HOSPITAL cost accounting.

PMID- 14955990
TI  - FOOT-and-mouth disease and birds.

PMID- 14955991
TI  - Search for epidemics of tuberculosis.

PMID- 14955992
TI  - PROSPECT of general practice, from a correspondent.

PMID- 14955993
TI  - Malarial fever therapy.

PMID- 14955995
TI  - HYPNOTIST'S successful appeal.

PMID- 14955994
TI  - FATAL injection of sulphuric acid.

PMID- 14955996
TI  - EDWARD Roland Garnett passe.

PMID- 14955997
TI  - HAROLD Ettrick Moore.

PMID- 14955998
TI  - Recent trends in the treatment of pulmonary tuberculosis.

PMID- 14955999
TI  - Superficial staphylococcal infection.

PMID- 14956000
TI  - Colles fracture of the radius; a method of treatment.

PMID- 14956001
TI  - Recognition of functional disorders of the small intestine.

PMID- 14956002
TI  - Lead paint: a hazard to children.

PMID- 14956004
TI  - Primary colostridial pneumonia; report of a case.

PMID- 14956003
TI  - Management of hypotension during anaesthesia.

PMID- 14956005
TI  - Experimental depletion of potassium in man.

PMID- 14956006
TI  - NEW ways with tuberculosis.

PMID- 14956007
TI  - CHLOROPHYLL as deodorant.

PMID- 14956008
TI  - PARAHAEMOPHILIA.

PMID- 14956009
TI  - ACTION of antibiotics.

PMID- 14956010
TI  - TWO types of mental defect?

PMID- 14956011
TI  - FORMATION of aneurysms.

PMID- 14956012
TI  - ANIMAL welfare legislation in America.

PMID- 14956013
TI  - The general practitioner and the laboratory service.

PMID- 14956014
TI  - BOOKS on hospitals.

PMID- 14956015
TI  - BONE regeneration.

PMID- 14956016
TI  - DEFAMATION proceedings.

PMID- 14956017
TI  - ALFRED Schweitzer.

PMID- 14956018
TI  - LIONEL Nathan Grunbaum.

PMID- 14956019
TI  - MR. H. E. Moore.

PMID- 14956020
TI  - Thoughts on medical education.

PMID- 14956021
TI  - Medical education in America.

PMID- 14956022
TI  - Education by travel.

PMID- 14956023
TI  - Tuberculosis in medical and dental students; a study at Guy's hospital.

PMID- 14956024
TI  - The physique of students; an experiment at Oxford.

PMID- 14956025
TI  - Selection of medical students; experiences at University College, London.

PMID- 14956026
TI  - The study group in teaching.

PMID- 14956027
TI  - LEARNING the art.

PMID- 14956028
TI  - EDUCATION and health.

PMID- 14956029
TI  - PRECLINICAL subjects: a wider approach.

PMID- 14956030
TI  - MEDICAL schools.

PMID- 14956031
TI  - POSTGRADUATE education.

PMID- 14956032
TI  - DEFENCE services.

PMID- 14956033
TI  - PUBLIC health.

PMID- 14956034
TI  - INDUSTRIAL medical services.

PMID- 14956035
TI  - SERVICES abroad.

PMID- 14956036
TI  - MEDICAL Research Council.

PMID- 14956037
TI  - The dangers of chronic inactivity in the aged.

PMID- 14956038
TI  - Conversion of tissue polysaccharides to auto-antigens by group-A beta-haemolytic
      streptococci.

PMID- 14956039
TI  - Deforming factors in the early stage of poliomyelitis.

PMID- 14956040
TI  - Salt-losing nephritis.

PMID- 14956041
TI  - The condition on the kidneys in salt-losing nephritis.

PMID- 14956042
TI  - Retardation of growth associated with Hirschsprung's disease.

PMID- 14956043
TI  - Treatment of the adrenogenital syndrome with cortisone.

PMID- 14956044
TI  - Thiopentone followed by nitrous oxide and oxygen for anaesthetizing outpatients.

PMID- 14956046
TI  - Modification of Bonney-Reverdin needle-holder.

PMID- 14956045
TI  - Tetraethyl lead poisoning; report of a non-fatal case.

PMID- 14956047
TI  - WHAT of general practice?

PMID- 14956048
TI  - ISONIAZID trials.

PMID- 14956049
TI  - ATROPINE alkaloids.

PMID- 14956050
TI  - DIURNAL excretory rhythm.

PMID- 14956051
TI  - VALVULOTOMY versus shunt.

PMID- 14956052
TI  - ISOTOPES in Britain.

PMID- 14956053
TI  - STREPTOCOCCI and rheumatism.

PMID- 14956054
TI  - SEX-hormone metabolism in liver disease.

PMID- 14956055
TI  - The need for an occupational hygiene service.

PMID- 14956056
TI  - MURDER and abnormality.

PMID- 14956057
TI  - Cure of tobacco-smoking.

PMID- 14956058
TI  - [Equilibrium of the autonomic nervous system in general anesthesia; discussion of
      syncurine-novocaine mixture].

PMID- 14956059
TI  - [Polycystic kidneys].

PMID- 14956060
TI  - [Cancer of the larynx].

PMID- 14956061
TI  - [Anesthesia in esophago-laryngectomy].

PMID- 14956062
TI  - [Comparative clinical study of two milk formulas; evaporated milk with dextri
      maltose; cow's milk with sugar].

PMID- 14956063
TI  - [A case of celiac disease].

PMID- 14956064
TI  - [Postoperative thromboembolism].

PMID- 14956065
TI  - [History of the Faculty of Medicine at Laval].

PMID- 14956066
TI  - [Advantages of fibrinolytic enzymes in thoracic surgery].

PMID- 14956067
TI  - [Resuscitation in cardiac respiratory syncope].

PMID- 14956068
TI  - [Voice without larynx; reeducation after laryngectomy].

PMID- 14956069
TI  - [Lobectomy for right apico-dorsal cavern in a 6-year-old girl; recovery].

PMID- 14956070
TI  - [Fibromyxosarcoma of the epiploon].

PMID- 14956071
TI  - [Pulsatile solitary tumor of the humeral diaphysis; possible metastasis of a
      clear cell cancer of the kidney].

PMID- 14956072
TI  - [National solidarity in the control of tuberculosis].

PMID- 14956073
TI  - [Conference on isonicotinic acid hydrazide].

PMID- 14956074
TI  - [Preliminary clinical results of the treatment of pulmonary tuberculosis with
      isonicotinic acid hydrazide; theoretical and practical considerations].

PMID- 14956075
TI  - [Anatomopathological modifications in patients treated with isonicotinic acid
      hydrazide].

PMID- 14956076
TI  - [Importance of the action of isonicotinic acid hydrazide].

PMID- 14956077
TI  - [Effect of isonicotinic acid hydrazide on arterial pressure in cat].

PMID- 14956078
TI  - [Value and signification of tuberculin reaction in school children].

PMID- 14956079
TI  - [Hemoptysis and endocrine disfunctions].

PMID- 14956080
TI  - [Respiratory function tests; comparative study on spirographic technic according
      to Knipping-Scoz method and on arterious oximetry].

PMID- 14956081
TI  - [Hilar adenopathy].

PMID- 14956082
TI  - [Antibiotics in osteoarticular tuberculosis; remote results].

PMID- 14956084
TI  - [Early diagnosis of pulmonary cancer].

PMID- 14956083
TI  - [Communications on isonicotinic acid hydrazide].

PMID- 14956085
TI  - [Pulmonary cysts].

PMID- 14956086
TI  - [Intravenous ACTH in bronchial asthma].

PMID- 14956087
TI  - [Testosterone propionate in silicotuberculosis].

PMID- 14956088
TI  - [Control of tuberculosis in the Province of Naples].

PMID- 14956089
TI  - [Ferruccio Banissoni].

PMID- 14956090
TI  - [The 15th National Campaign Against Tuberculosis in 1952].

PMID- 14956091
TI  - [Bronchographic aspect of two cicatrices of lymphnode fistula in an adult].

PMID- 14956092
TI  - [Ancylostomo-therapy in Vaquez disease; good hematological result; ancylostoma
      survival of more than four years].

PMID- 14956093
TI  - [Limitation of the crossed genu-pectoral position as first symptom of
      coxarthrosis].

PMID- 14956094
TI  - [Two cases of suppuration of the lumbar region caused by digestive disorder].

PMID- 14956095
TI  - [Pleuro-pulmonary ornitho-psittacosis with puriform pleural effusion; case
      report].

PMID- 14956096
TI  - [Retention of urine in spina bifida occulta].

PMID- 14956097
TI  - [Perforated duodenal ulcer in a newborn infant].

PMID- 14956098
TI  - [A case of allergic subsepsis treated with pyramidon].

PMID- 14956099
TI  - [The choice of remedy in infectious diseases].

PMID- 14956100
TI  - [Spontaneous hypoglycemia and hyperinsulinism in infants and children. II].

PMID- 14956101
TI  - [Spontaneous hypoglycemia and hyperinsulinism in infants and children. III].

PMID- 14956102
TI  - [Arteriovenous fistula in the area of the pulmonary artery].

PMID- 14956103
TI  - [Considerations on disorders of the electrolyte maintenance in a newborn infant
      with uremia].

PMID- 14956104
TI  - [Congress on Amebiasis, held at Fez, April 6 and 7 1952].

PMID- 14956105
TI  - [Amebiasis, intestinal flora and associated parasitoses].

PMID- 14956106
TI  - [Modern therapy of amebiasis].

PMID- 14956107
TI  - [Treatment of colitis by antibiotics, especially aureomycin].

PMID- 14956108
TI  - [Healthy carriers of amebae].

PMID- 14956109
TI  - [Amebic dysentery and infants].

PMID- 14956110
TI  - [Laboratory diagnosis of human amebiasis; errors caused by hyper-parasitization
      of amebae by chytridiaceae].

PMID- 14956111
TI  - [Intradermal reaction for diagnosis of amebiasis].

PMID- 14956112
TI  - [Amebic abscess of the lung].

PMID- 14956113
TI  - [Acute pneumopathy of probable amebic origin].

PMID- 14956115
TI  - [Pseudo-neoplasm of the colon of amebic etiology].

PMID- 14956114
TI  - [A case of arthritis of amebic origin].

PMID- 14956116
TI  - [Chronic amebiasis with renal symptoms].

PMID- 14956117
TI  - [Chronic amebiasis and diabetes mellitus].

PMID- 14956118
TI  - [Cutaneous reactions in amebiasis].

PMID- 14956119
TI  - [Thermic cures of chronic amebiasis and its sequels].

PMID- 14956120
TI  - [Patient psychology in Fez].

PMID- 14956121
TI  - [Dysentery in the writings of ancient Arabian physicians].

PMID- 14956122
TI  - [Dysentery in writings of Avenzoar].

PMID- 14956123
TI  - [Swin pest; a note on variability of the virus].

PMID- 14956124
TI  - [Toxicity of an acrid powder with a hexachlorocyclohexane base to horses].

PMID- 14956125
TI  - [Receptivity of autochthonous Moroccan beef to the foot-and-mouth disease virus].

PMID- 14956126
TI  - [The balance-sheet of science for the half century].

PMID- 14956127
TI  - [Pathology and surgery of the esophagus].

PMID- 14956128
TI  - [Hydatid cyst of the lung and tuberculosis].

PMID- 14956129
TI  - [Medico-surgical anatomy of esophageal-cardial tuberosity].

PMID- 14956130
TI  - [Myopathic myasthenia syndrome treated with total thymectomy and enervation of
      the carotid sinus].

PMID- 14956131
TI  - [Traumatic aneurysm of the superficial temporal artery].

PMID- 14956132
TI  - [Sciatica caused by meningioma of the cauda equina].

PMID- 14956133
TI  - [Lithiasic dilation of the intra-hepatic bile ducts].

PMID- 14956134
TI  - [Peptic ulcer of the jejunum; multi-stage operation; recovery].

PMID- 14956135
TI  - [The meaning of angor and the place of inferior vena cava ligature in thrombo
      embolisms].

PMID- 14956136
TI  - [Debridement of the femoral ring in therapy of chronic elephantiasic edema of the
      lower limb].

PMID- 14956137
TI  - [Potentialized anesthesia in gastrointestinal surgery; clinical study].

PMID- 14956138
TI  - [Sympathetic surgery in cerebral vascular disorders].

PMID- 14956139
TI  - [Sub-total colectomy in a 4-year-old girl].

PMID- 14956140
TI  - [Febrile jaundice and hydatid cyst of the liver; importance of per-operative
      cholangiography].

PMID- 14956141
TI  - [Non-parasitic hepatomegaly discovered in remote postoperative sequelae of
      hydatid cyst of the liver].

PMID- 14956142
TI  - [Exteriorized hydatid cyst of the lower left lobe of the lung; cystectomy].

PMID- 14956143
TI  - [Intra-cerebral spontaneous hematomas; report on 12 cases].

PMID- 14956144
TI  - [Traumatic acillary aneurysms].

PMID- 14956145
TI  - [Adrenalectomy in Raynaud's disease].

PMID- 14956146
TI  - [Cutaneous reactions to tuberculin].

PMID- 14956147
TI  - [Relapses in the evolution of pulmonary tuberculosis treated in sanatorium].

PMID- 14956148
TI  - [Initial symptoms of chronic pulmonary tuberculosis in adults].

PMID- 14956149
TI  - [Technique, indications and results of 31 segmentary pulmonary exereses].

PMID- 14956150
TI  - [Effect of phenergan on the cutaneous reaction of the guinea pig to tuberculin].

PMID- 14956151
TI  - [Reactivation of a focus of primary infection by iterative cuti-reactions].

PMID- 14956152
TI  - [Results of cutaneous tests with tuberculin in students].

PMID- 14956153
TI  - [Pneumoconiotuberculosis of broom makers].

PMID- 14956154
TI  - [Etiological and physio-pathological ideas of non-silicotic pneumoconiosis].

PMID- 14956155
TI  - [Relapse in situ during treatment of pulmonary tuberculosis by artificial
      pneumothorax].

PMID- 14956156
TI  - [Bilateralization during medical therapeutic pneumothorax].

PMID- 14956157
TI  - [Paramediastinal round shadows].

PMID- 14956158
TI  - [Treatment of asthma by the Benda and Urquia method].

PMID- 14956159
TI  - [Segmentary exeresis: a case of apico-dorsal exeresis in tuberculosis].

PMID- 14956160
TI  - [PAS therapy in pulmonary tuberculosis].

PMID- 14956161
TI  - [Dean Lucien Cornil].

PMID- 14956162
TI  - [Chronic bronchial diseases and their treatment].

PMID- 14956163
TI  - [Current ideas on the physiology of the adrenal cortex].

PMID- 14956164
TI  - [Recent data on the pathology of the adrenal cortex].

PMID- 14956165
TI  - ONE hundred fifty-fourth annual meeting Medical and Chirurgical Faculty of the
      State of Maryland.

PMID- 14956166
TI  - Past-present-future.

PMID- 14956167
TI  - COMMITTEE for the Study of Pelvic Cancer.

PMID- 14956168
TI  - Unity for a faith.

PMID- 14956169
TI  - How the library can serve the physician.

PMID- 14956170
TI  - A discussion of some of the problems associated with licensure.

PMID- 14956171
TI  - COMMITTEE for the Study of Pelvic Cancer.

PMID- 14956172
TI  - No longer our ivory towers.

PMID- 14956173
TI  - The physician against atomic attack.

PMID- 14956174
TI  - Cortisone (cortone) in the treatment of acute subdeltoid bursitis.

PMID- 14956175
TI  - Thirty years of phytopharmacology or applications of plant physiology to medical
      problems.

PMID- 14956176
TI  - SYMPOSIUM on the doctor in court.

PMID- 14956177
TI  - Expert testimony from the viewpoint of trial counsel.

PMID- 14956178
TI  - Expert testimony from the viewpoint of industrial medicine.

PMID- 14956179
TI  - Expert testimony from the viewpoint of traumatic surgery.

PMID- 14956180
TI  - President's report to the board of trustees.

PMID- 14956181
TI  - COMMITTEE for the Study of Pelvic Cancer.

PMID- 14956182
TI  - COMMITTEE to cooperate with the American Medical Education Foundation.

PMID- 14956183
TI  - PANEL discussion: thyroid.

PMID- 14956184
TI  - Psychiatry.

PMID- 14956185
TI  - Surgery.

PMID- 14956186
TI  - Internal medicine.

PMID- 14956187
TI  - Pathology.

PMID- 14956188
TI  - Radioactive iodine.

PMID- 14956189
TI  - QUESTION and answer period.

PMID- 14956190
TI  - Lingual thyroid.

PMID- 14956191
TI  - MARYLAND State Department of Health; some changes in communicable disease
      reporting.

PMID- 14956192
TI  - STATE of Maryland Department of Health monthly communicable disease report; case
      reports received during 4-week period, March 21-April 17, 1952.

PMID- 14956193
TI  - The Maryland County Medical Care Program--a progress report.

PMID- 14956195
TI  - The doctor-citizen in 1952.

PMID- 14956194
TI  - Committee for the Study of Pelvic Cancer.

PMID- 14956196
TI  - Salt.

PMID- 14956197
TI  - SYMPOSIUM on the doctor in court.

PMID- 14956198
TI  - Expert testimony from the viewpoint of psychiatry.

PMID- 14956199
TI  - Expert testimony from the viewpoint of the jurist.

PMID- 14956200
TI  - Abscess of the lung due to endamoeba histolytica treated by surgery and
      aureomycin.

PMID- 14956202
TI  - HINTS for medical writers.

PMID- 14956201
TI  - Bookplates--the Finney Fund.

PMID- 14956203
TI  - Maryland Hospital Service, Inc.

PMID- 14956204
TI  - DR. Alfred Ullman--a tribute.

PMID- 14956205
TI  - Problems of practice.

PMID- 14956206
TI  - The problem of jaundice in general surgery.

PMID- 14956207
TI  - Medicine's number one problem.

PMID- 14956208
TI  - SELECTED bibliography; geriatrics.

PMID- 14956209
TI  - OSLER funds.

PMID- 14956210
TI  - Maryland.

PMID- 14956211
TI  - STATE of Maryland Department of Health monthly communicable disease report case
      reports received during 4 week period, May 2-29, 1952.

PMID- 14956212
TI  - Blue Cross.

PMID- 14956213
TI  - Trends in hospital out-patient care.

PMID- 14956214
TI  - Medical education and medical research are part and parcel of the medical
      profession.

PMID- 14956215
TI  - HOUSE of Delegates: special session Monday, April 28, 1952, 2:00 p.m.

PMID- 14956216
TI  - STATE of Maryland Department of Health monthly communicable disease report.

PMID- 14956217
TI  - [Experimental studies on the effect of industrial dust on the lungs].

PMID- 14956218
TI  - [Pneumoconioses of quarrymen and limestone cutters].

PMID- 14956219
TI  - [Silicatoses, observations on talc and kaolin].

PMID- 14956220
TI  - [Problems of prevention of silicosis in stone-yards with hydro-electric
      equipment].

PMID- 14956221
TI  - [Account on an experience of reclassification of the unfit rejected by the
      factory physician].

PMID- 14956222
TI  - [The industrial medicine mobile and its patients].

PMID- 14956223
TI  - [Preliminary note on the selection of drivers of public vehicles].

PMID- 14956224
TI  - [Visual acuity and industrial medicine].

PMID- 14956225
TI  - [Heterophoria in industrial medicine].

PMID- 14956226
TI  - [Equipment of a small mobile unit in the industrial medico-social service of a
      medium size province].

PMID- 14956227
TI  - [Dermatologic lesions cause by rock-wool].

PMID- 14956228
TI  - [Handling of flintkote].

PMID- 14956229
TI  - [Transpulmonary medication].

PMID- 14956230
TI  - [The duties of industrial physicians].

PMID- 14956231
TI  - [Rhinitis and perforations of the nasal septum in sulphuric acid and
      superphosphate factories].

PMID- 14956232
TI  - [Role of industrial physicians in the prevention of on-the-job accidents].

PMID- 14956234
TI  - [Decree of 12 December 1950 fixing conditions of agreement for the inspection of
      electric installations].

PMID- 14956233
TI  - [Law no. 50-905 of August 4, 1950 organizing the liaison and coordination of
      social services].

PMID- 14956235
TI  - [Industrial circular No. 28/50 of 22 December 1950 concerning labeling of harmful
      substances in industrial use].

PMID- 14956236
TI  - [Pulmonary cancer and exposure to vapor of heated industrial oils].

PMID- 14956237
TI  - [Prevention of proximity risks].

PMID- 14956238
TI  - [Glass fiber and its derivatives].

PMID- 14956239
TI  - [A case of tumoral silicosis treated with nitrogen mustard].

PMID- 14956240
TI  - [Human problems in industry and industrial medicine at the Tenth Congress of
      Industrial Medicine].

PMID- 14956241
TI  - [Protection of the health of workers].

PMID- 14956242
TI  - [International action in favor of intellectual workers].

PMID- 14956243
TI  - [Decree No. 50-1304 of 20 October 1950 providing public administrative regulation
      concerning the special statute of the labor and manpower inspection corps].

PMID- 14956244
TI  - [Circular No. 128 S.S. 1950 of 26 June 1950 concerning loans granted to health
      establishments such as open air and preventive hospitals and sanatoria, as well
      as subsidized funds for the care of the patients admitted to such
      establishments].

PMID- 14956245
TI  - [Circular TR 1/50 of 29 January 1951 concerning the application of regulations
      relating to protection from dangerous machines to sellers of secondhand
      machinery].

PMID- 14956246
TI  - [Dietetics and industrial medicine].

PMID- 14956247
TI  - [Hypotensive nephelo-therapy; physiology of aerosols].

PMID- 14956248
TI  - [Asthma in welding].

PMID- 14956249
TI  - [Human labor problems and industrial pathology at the Tenth Congress of
      Industrial Medicine. II. Industrial diseases].

PMID- 14956250
TI  - [One can compare psychosurgery with any other surgical intervention intended to
      alleviate suffering].

PMID- 14956251
TI  - [Lobotomy remains an effective act by its results].

PMID- 14956252
TI  - [Psychosurgery permits the cure of patients].

PMID- 14956253
TI  - [Lobotomy never cures schizophrenia].

PMID- 14956254
TI  - [Quinine and the synthetic antimalarials].

PMID- 14956255
TI  - [The pituitary growth hormone].

PMID- 14956256
TI  - [A eugenic code in Finland].

PMID- 14956257
TI  - [Peptolactin].

PMID- 14956258
TI  - [Empirical medications and hormonal therapeutics in so-called infections
      rheumatisms].

PMID- 14956259
TI  - [Vertebral traction].

PMID- 14956260
TI  - [The second European Congress of Rheumatology].

PMID- 14956261
TI  - [The endocrine aspects of rheumatism].

PMID- 14956262
TI  - [Ankylosing spondylitis].

PMID- 14956263
TI  - [Ultrasonics].

PMID- 14956264
TI  - [The place of sauna in the prophylaxis and treatment of rheumatic disease].

PMID- 14956265
TI  - [The role of thermal cure].

PMID- 14956266
TI  - [Blood sedimentation in amebiasis. II. The practical application of blood
      sedimentation to diagnosis, to prognosis and to the guidance of treatment in
      amebic disease].

PMID- 14956267
TI  - [Anatomico-clinical and neurosurgical considerations on the first series of
      intracranial tumors observed in the Far East].

PMID- 14956268
TI  - [The danger of using dicumarol in the pregnant woman].

PMID- 14956269
TI  - [Indication and choice of antibiotics in the treatment of infectious diseases in
      the practice of exotic medicine].

PMID- 14956270
TI  - [Notes concerning a non-perforate lamellar keratoplasty].

PMID- 14956271
TI  - [Tannin containing plants of French Oceania].

PMID- 14956272
TI  - [The rehydration of a nursing infant in colonial practice].

PMID- 14956273
TI  - [The prosthesis of the amputees in Germany and Austria].

PMID- 14956274
TI  - [Antimosquito control by spraying of DDT].

PMID- 14956275
TI  - [Malaria].

PMID- 14956276
TI  - [Contributions to sleeping sickness].

PMID- 14956277
TI  - [The dangers in surgical delay in abscesses of the liver].

PMID- 14956278
TI  - [Genital forms of Bancroft's filariasis in French Guiana].

PMID- 14956279
TI  - [Study of the urinary excretion of neutral 17-ketosteroids in normal and with
      trypanosoma infected African].

PMID- 14956280
TI  - [Pulmonary tropical eosinophilia].

PMID- 14956281
TI  - [A case of benign inoculation lymphoreticulosis in Tchad].

PMID- 14956282
TI  - [Therapy of acute hepatic amebiasis and of plague].

PMID- 14956283
TI  - Inhalational therapy.

PMID- 14956284
TI  - The use and abuse of some new drugs.

PMID- 14956285
TI  - The electrocardiographic manifestations of coronary artery heart disease.

PMID- 14956286
TI  - Marital conflict and functional illness.

PMID- 14956287
TI  - Resolution of a paranoid psychosis.

PMID- 14956288
TI  - Rehabilitation demonstration project at Gallinger Municipal Hospital.

PMID- 14956289
TI  - Progress in medical technology.

PMID- 14956290
TI  - MERRITTE Weber Ireland, M.D., LL.D., F.A.C.P., F.A.C.S. (1867-1952).

PMID- 14956291
TI  - WALTER Hibbard Merrill, L.B.,M.D. (1873-1952).

PMID- 14956292
TI  - GREGG Custis Birdsall, B.S., M.D. (1883-1952).

PMID- 14956293
TI  - JOHN Paul Gunion, M.D. (1876-1952).

PMID- 14956294
TI  - The decorated woodcut initials of Vesalius' "Fabrica".

PMID- 14956295
TI  - Co-operation between author, publisher, and illustrator.

PMID- 14956297
TI  - Gross specimen photography; a review.

PMID- 14956296
TI  - Preparing illustrations for halt-tone reproduction.

PMID- 14956298
TI  - The Duguid-Young technique for making plastic specimen containers.

PMID- 14956299
TI  - Medical application of phase-contrast microscopy.

PMID- 14956300
TI  - Photographing glass and perspex for publication.

PMID- 14956301
TI  - Reflector attachment for a head-rest.

PMID- 14956302
TI  - A nomogram for flash guide numbers.

PMID- 14956303
TI  - The mortality in Australia from cancers peculiar to the male.

PMID- 14956304
TI  - Toxoplasmosis: a review with a report of three cases.

PMID- 14956305
TI  - Some impressions of group psychotherapy.

PMID- 14956306
TI  - The backlash of change.

PMID- 14956307
TI  - Psychopathic personality.

PMID- 14956308
TI  - The anaemias: treatment.

PMID- 14956309
TI  - Crohn's disease of the colon.

PMID- 14956310
TI  - Transference and counter-transference in psychoanalytical therapy.

PMID- 14956311
TI  - James Spittal Buchanan.

PMID- 14956312
TI  - DISEASES notified in each State and Territory of Australia for the week ended
      June 14, 1952.

PMID- 14956313
TI  - The role of A B O incompatibility as a cause of erythroblastosis foetalis, with
      report of a case.

PMID- 14956314
TI  - Chronic rheumatic (rheumatoid) monarthritis.

PMID- 14956315
TI  - Response of the male toad Bufo marinus, to chorionic gonadotropin and use of the
      animal for biological assay.

PMID- 14956316
TI  - The mechanism of results in treatment with ACTH and cortisone.

PMID- 14956317
TI  - Irukandji sting to North Queensland bathers without production of weals but with
      severe general symptoms.

PMID- 14956318
TI  - Two cases of complete transposition of the great vessels of the heart.

PMID- 14956319
TI  - The bilious attack.

PMID- 14956320
TI  - RADIOACTIVE iodine and thyroid disease.

PMID- 14956321
TI  - Gastric tumours.

PMID- 14956322
TI  - DISEASES notified in each State and Territory of Australia for the week ended
      June 21, 1952.

PMID- 14956323
TI  - The dog and the shadow.

PMID- 14956324
TI  - Abdominal pain in infancy.

PMID- 14956325
TI  - Medical causes of abdominal pain during childhood.

PMID- 14956326
TI  - Abdominal pain in childhood from the surgical angle.

PMID- 14956327
TI  - Megaloblastic anaemia of infancy.

PMID- 14956328
TI  - Weber-Christian syndrome; report of a case.

PMID- 14956329
TI  - A case of pancreatic calcification.

PMID- 14956330
TI  - A case of meningioma of the olfactory groove with mental changes.

PMID- 14956331
TI  - Cystic ganglioneuroma.

PMID- 14956333
TI  - RETICULOSES.

PMID- 14956332
TI  - The problem of adolescence.

PMID- 14956334
TI  - Some aspects of flexor tendon repair.

PMID- 14956335
TI  - PAEDIATRIC trends overseas.

PMID- 14956336
TI  - DISEASES notified in each State and Territory of Australia for the week ended
      June 28, 1952.

PMID- 14956337
TI  - [Spastic hypertonia in clinical medicine].

PMID- 14956338
TI  - [Syndrome of alimentary hemolysis and its distribution in Spain].

PMID- 14956339
TI  - [Science and conscience of ophthalmic indication and corneal graft].

PMID- 14956340
TI  - [Antihistaminics in the treatment of acute diffuse nephritis; bases and results].

PMID- 14956341
TI  - [Case of perforation of the uterus diagnosed by laparotomy].

PMID- 14956342
TI  - [Case of human hydatidosis of unusual evolution].

PMID- 14956343
TI  - [Proctitis due to chloramphenicol].

PMID- 14956344
TI  - [Discovery of blood circulation in 1546 by the Spaniards Francisco de la Reyna
      and Miguel Servet].

PMID- 14956345
TI  - [Differential diagnosis between authentic febricula and dysthermia].

PMID- 14956346
TI  - [Psychoanalysis, the medicine of totality and its arguments].

PMID- 14956347
TI  - [New theory and treatment of strophulus].

PMID- 14956348
TI  - [Present state of the treatment of urinary lithiasis].

PMID- 14956349
TI  - [General medical criteria of congenital heart disease].

PMID- 14956350
TI  - [Surgical pathology of subphrenic abscesses].

PMID- 14956351
TI  - [Case of allergic cellulitis].

PMID- 14956352
TI  - [Case of gonococcic cervicitis and pregnancy].

PMID- 14956353
TI  - [New unusual case of foreign body in the esophagus].

PMID- 14956354
TI  - [Investigation technics for Trichomonas, Chilomastix and Giardias].

PMID- 14956355
TI  - [Alderete and Mendez Nieto; two physicians of the 16th century].

PMID- 14956356
TI  - [Chronic Chagas cardiopathy].

PMID- 14956357
TI  - [Epilepsy in twins].

PMID- 14956358
TI  - [Pulmonary syphilitic aortitis and arteritis; syndrome of inverted coarctation of
      the aortic isthmus and pulmonary arterial hypertension].

PMID- 14956359
TI  - [Foundation of the Institute of Experimental Biology].

PMID- 14956360
TI  - [Peptic ulcer in Bogota; statistical studies on 516 cases diagnosed by the
      department of gastroenterology at the I.C.S.S. in 1950-51].

PMID- 14956361
TI  - [Anatomoclinical conference at the Hospital San Juan de Dios; ileus].

PMID- 14956362
TI  - [Medical aspects of atomic warfare].

PMID- 14956363
TI  - [Metabolic rheumatisms].

PMID- 14956364
TI  - [Various clinical forms of Crohn's disease and their treatment].

PMID- 14956365
TI  - [Internal medicine as a speciality].

PMID- 14956366
TI  - [Injuries of the ureter].

PMID- 14956367
TI  - [Clinical note; secondary atypical syphilis].

PMID- 14956368
TI  - [Surgical note; postoperative pulmonary atelectasis].

PMID- 14956369
TI  - [Clinical speciality note; esophageal syndrome due to fistulizing abscess of the
      wall].

PMID- 14956370
TI  - MIGUEL Augusto Bombarda--1852-1952.

PMID- 14956371
TI  - [Miguel Bombarda, his personality and teachings].

PMID- 14956372
TI  - [Miguel Bombarda and psychiatric assistance].

PMID- 14956373
TI  - [Homage to Bombarda at the 28 February 1952 session of the Neuropsychiatric
      Society].

PMID- 14956374
TI  - [Miguel Bombarda, man of his time].

PMID- 14956375
TI  - [Strychnine poisoning in mice].

PMID- 14956376
TI  - [Case of spinal cord compression caused by Paget's disease].

PMID- 14956377
TI  - [50th Anniversary of the Ricardo Jorge Institute].

PMID- 14956378
TI  - [Radiology of the stomach and simulation of various conditions].

PMID- 14956379
TI  - [Egas Moniz Clinic of Jacarepagua].

PMID- 14956380
TI  - [The drop sign in retrograde pyelography with oil contrast media].

PMID- 14956381
TI  - [Histaminolytic property of the blood of normal pregnant women in late
      pregnancy].

PMID- 14956382
TI  - [Importance of nutrition in atherosclerosis].

PMID- 14956383
TI  - [Low-fat and low-cholesterol diets].

PMID- 14956384
TI  - [Daily food consumption per capita in Portugal].

PMID- 14956385
TI  - [Tumors of diverticula of the bladder].

PMID- 14956386
TI  - [Pubovesical drainage].

PMID- 14956387
TI  - [Strychnine and tuberculosis in mice].

PMID- 14956388
TI  - [Intravenous iron therapy].

PMID- 14956389
TI  - [17 years of struggle].

PMID- 14956390
TI  - [Concept of industrial medicine in France].

PMID- 14956391
TI  - [50 years of industrial medicine].

PMID- 14956392
TI  - Surgical lesions of the spine.

PMID- 14956393
TI  - [Nutritional assistance to workers].

PMID- 14956394
TI  - [Legal control of unhealthy working conditions in Brazil].

PMID- 14956395
TI  - [The science of work].

PMID- 14956396
TI  - [Criterion of occupational guidance].

PMID- 14956397
TI  - [Postcommotional syndromes in industrial accidents].

PMID- 14956398
TI  - [Social protection of women in industry].

PMID- 14956399
TI  - Evaluation of disabilities for compensation.

PMID- 14956400
TI  - [Review of results of surgical treatment of pulmonary tuberculosis].

PMID- 14956401
TI  - [Certain observations on the excretion of endogenous cortisone in man].

PMID- 14956402
TI  - [Virus as a chemical agent].

PMID- 14956403
TI  - [Probable case of rabies in a domesticated rat].

PMID- 14956404
TI  - [International Day of Health, 7 April, 1952].

PMID- 14956405
TI  - [Rocky Mountain spotted fever in Mexico].

PMID- 14956406
TI  - [Asthma and climate].

PMID- 14956408
TI  - [Progress in the treatment of bladder diseases].

PMID- 14956407
TI  - [Intravenous terramycin in the treatment of peritonitis due to perforation of the
      intestine in typhoid fever].

PMID- 14956409
TI  - [Sanitary and hygienic education].

PMID- 14956410
TI  - [Flies and control of insects].

PMID- 14956411
TI  - [Milk handling].

PMID- 14956412
TI  - [Certain toxoplasmo-reactions in leprosy].

PMID- 14956413
TI  - [Equine onchocercosis in Mexico].

PMID- 14956414
TI  - [Coxsackie virus; isolation and properties].

PMID- 14956415
TI  - [Multiplication and variations of viruses].

PMID- 14956417
TI  - [Food handling and eating habits].

PMID- 14956416
TI  - [Ulcerative colitis].

PMID- 14956418
TI  - [Sanitary installations and their contribution to health].

PMID- 14956419
TI  - [General-adaptation syndrome and ACTH and cortisone].

PMID- 14956420
TI  - [Studies on Rocky Mountain spotted fever in Mexico; natural infection of
      hematophagous parasites].

PMID- 14956421
TI  - [Immunological classification of poliomyelitis viruses].

PMID- 14956422
TI  - [Development and future of the World Health Organization].

PMID- 14956423
TI  - [Pure water supply].

PMID- 14956424
TI  - [Housing and hygiene].

PMID- 14956425
TI  - [Effect of terramycin in pinta].

PMID- 14956426
TI  - [Discovery of microfilarias of Onchocerca cervicalis in the ocular tissue in
      horse].

PMID- 14956427
TI  - [Experimental studies on BCG vaccine].

PMID- 14956428
TI  - [Elimination of smallpox in Mexico].

PMID- 14956429
TI  - [400 Years of smallpox].

PMID- 14956430
TI  - [New concepts of the etiopathogenesis and of the treatment of acute simple
      prurigo in children].

PMID- 14956431
TI  - [Certain aspects of ecology of Simulium larvae in relation to transmission on
      Onchocerca volvulus in Chiapas].

PMID- 14956432
TI  - [Public cooperative medical and sanitary services of the Secretaria de
      Salubridad].

PMID- 14956433
TI  - [Roentgen irradiation of the adrenal gland].

PMID- 14956434
TI  - [Louis Pasteur as a scientist and as a man].

PMID- 14956435
TI  - [Present state of streptomycin therapy of tuberculosis].

PMID- 14956436
TI  - [Diagnosis and treatment of prostatic carcinoma].

PMID- 14956437
TI  - [Penicillin therapy of suppurative processes].

PMID- 14956438
TI  - [Therapeutic use of male sex hormones in women and of female sex hormones in
      men].

PMID- 14956439
TI  - [Sodium pentothal as intravenous anesthetic].

PMID- 14956440
TI  - [Exactness of hematometer].

PMID- 14956441
TI  - [Indications and contraindication in the treatment of gastrointestinal diseases
      with mineral water].

PMID- 14956442
TI  - [Symposium and physiological and clinical effects of radioactive isotopes].

PMID- 14956443
TI  - [Etiopathogenesis and therapy of Leiner's erythroderma desquamativum].

PMID- 14956444
TI  - [Anesthesiologist's errors in jurisprudence].

PMID- 14956445
TI  - [Clinical evaluation of liver function tests].

PMID- 14956446
TI  - [Certain considerations on the technic of tooth extraction].

PMID- 14956447
TI  - [Politico-educational activities among nurses].

PMID- 14956448
TI  - [First aid in industrial accidents].

PMID- 14956449
TI  - [Rickets, in prevention and therapy].

PMID- 14956450
TI  - [Certain facts on strabismus].

PMID- 14956451
TI  - [Nikolai Aleksandrovich Semakhko; 3rd anniversary of his death].

PMID- 14956452
TI  - [Manifestations and therapy of ovarial insufficiency].

PMID- 14956453
TI  - [Therapy of alopecia areata].

PMID- 14956454
TI  - [Diagnosis and evaluation of closed brain injury with minor symptoms].

PMID- 14956455
TI  - [Fatty acids with several unsaturated groups in the therapy of parenchymal liver
      diseases].

PMID- 14956456
TI  - [Burning of tongue and allergy].

PMID- 14956457
TI  - [Pathological importance of dysbacteria of the large intestines].

PMID- 14956458
TI  - [Observations in phenothiazin treatments in children].

PMID- 14956459
TI  - [Local circulatory therapy and general application of irritants in rheumatic
      diseases].

PMID- 14956460
TI  - [Psychosomatic effects of a pilgrimage to Lourdes].

PMID- 14956461
TI  - [Lourdes].

PMID- 14956462
TI  - [Problems of goiter and hyperthyroidism].

PMID- 14956463
TI  - [Surgical therapy of esophageal diseases].

PMID- 14956464
TI  - [Modern development of cardiovascular surgery].

PMID- 14956465
TI  - [The acute abdomen].

PMID- 14956466
TI  - [Conservative therapy of the prolapsed disc].

PMID- 14956467
TI  - [Diseases of cervical intervertebral discs].

PMID- 14956468
TI  - [Alloplastic surgery of the hip joint with the Judet method].

PMID- 14956469
TI  - [Modern therapy of osteoarticular tuberculosis].

PMID- 14956470
TI  - [Rimifon Roche, a new tuberculostatic drug].

PMID- 14956471
TI  - [A new resorbable material in wound therapy].

PMID- 14956472
TI  - [Experiences with a new resorbable gauze compress made of neutralized
      oxycellulose].

PMID- 14956473
TI  - [Desantigenated animal sera used as plasma substitutes].

PMID- 14956474
TI  - [On nephritis and nephrosis].

PMID- 14956475
TI  - [The problem of experimental liver damage].

PMID- 14956476
TI  - [Effects of ACTH and cortisone in infections diseases].

PMID- 14956477
TI  - [Bronchial asthma and service disability].

PMID- 14956478
TI  - [Hemorrhagic diatheses of childhood].

PMID- 14956479
TI  - [Intravenous normal plasma injections in the therapy of hemorrhagic
      manifestations of hemophilics].

PMID- 14956480
TI  - [Effects of strychnine on circulatory dysregulations].

PMID- 14956481
TI  - [Experiments to increase the penicillin effects by omnadin].

PMID- 14956482
TI  - [Experimental investigations on the effects of penicillin and omnadin-penicillin
      on the antibody-titer].

PMID- 14956483
TI  - [Some comments on the May-Gruenwald-Giemsa staining of blood and organ
      preparations].

PMID- 14956484
TI  - [Parasitology, pathology and therapy of helminthiasis in Paulos Aiginetes].

PMID- 14956485
TI  - [The word physicians in a dictionary on fraud].

PMID- 14956486
TI  - [Problems of modern balneology].

PMID- 14956487
TI  - [Natural and artificial aerosols].

PMID- 14956488
TI  - [Importance and problems of the science of trace elements].

PMID- 14956490
TI  - [Balneology in Switzerland].

PMID- 14956489
TI  - [Goals and ways of scientific balneology].

PMID- 14956491
TI  - [Physician and medical climatology].

PMID- 14956492
TI  - [New West German spaas].

PMID- 14956493
TI  - [Tissue and body temperature in mud packings and partial mud baths].

PMID- 14956494
TI  - In memoriam Prof. Franz Groedel.

PMID- 14956495
TI  - In memoriam Prof. G. Boehm.

PMID- 14956496
TI  - [Not Available].

PMID- 14956497
TI  - [Role of intracellular accumulation of cholesterol in the intima and
      extracellular precipitation of cholesterol in the deeper layers of the blood
      vessel wall in the pathogenesis of blood vessel damage].

PMID- 14956498
TI  - [Malignant angiosclerosis caused by endocrine disorders; demonstration of the
      adrenal and renal pathogenesis of hypertension].

PMID- 14956499
TI  - [Vasoaffinity of sexual hormones].

PMID- 14956500
TI  - [Anticoagulant therapy over a long period].

PMID- 14956501
TI  - [Differential diagnostic value of the precipitation count in the blood and
      ascites; cancer diagnosis].

PMID- 14956502
TI  - [Simple methods to diagnose cardiac diseases].

PMID- 14956503
TI  - [Renal function and circulation in cardiac patients].

PMID- 14956505
TI  - [Pain in vertebral column].

PMID- 14956504
TI  - [Hypoproteinemia with edema in gastrointestinal diseases].

PMID- 14956506
TI  - [The meaning of disease entity].

PMID- 14956507
TI  - [Not Available].

PMID- 14956508
TI  - [Franz Volhard as teacher].

PMID- 14956509
TI  - [Problems of allergy. X. Allergy causing occupational dermatoses].

PMID- 14956510
TI  - [Effects of hyaluronidase on blood-spinal fluid barrier].

PMID- 14956511
TI  - [Illegitimate pregnancy in minors; a sociological study].

PMID- 14956512
TI  - [Therapy of painful conditions of the hip joint by directed injections].

PMID- 14956513
TI  - [Asymmetric and symmetric form of the status Bonnevie-Ullrich].

PMID- 14956514
TI  - [Experimental and therapeutic investigations in orthostatic circulatory failure].

PMID- 14956515
TI  - [Traumatic extrapulmonal metastatic tuberculosis; originating from traumatic
      chronic tuberculous otitis media].

PMID- 14956516
TI  - [Therapeutic abortion in the decisions of the Federal Court].

PMID- 14956517
TI  - [Not Available].

PMID- 14956518
TI  - [Partial kidney infarction and hypertension caused by ligation of accessory blood
      vessels].

PMID- 14956519
TI  - [Myocardosis--a new entity in evaluation of heart diseases].

PMID- 14956520
TI  - [Poisoning with beta-, beta dichlordiethylsulfid].

PMID- 14956521
TI  - [Kux's oleopericardium to avoid pericardial obliterations].

PMID- 14956522
TI  - [Effects of hydrogenated secale alkaloids on cerebral blood supply of the cat].

PMID- 14956523
TI  - [Therapy and prophylaxis of thromboembolism with venostasin].

PMID- 14956524
TI  - [Experiences with the new short acting anesthetic isopropylchloride].

PMID- 14956525
TI  - [A new method to remove necrotic tissue].

PMID- 14956526
TI  - [The typical x-ray picture of the thorax and the lungs].

PMID- 14956527
TI  - [Not Available].

PMID- 14956528
TI  - [Strabismus and its therapy].

PMID- 14956529
TI  - [Therapy of strictures of the esophagus].

PMID- 14956530
TI  - [Dental focal infection].

PMID- 14956531
TI  - [Orthopedic therapy of poliomyelitis].

PMID- 14956532
TI  - [Strophanthin therapy of the early cardiac insufficiency].

PMID- 14956533
TI  - [Dependence of anti-body reaction from nerval tissue].

PMID- 14956534
TI  - [Experiences with polyvital and polyvital forte; roborizing effects of vitamin B
      complex].

PMID- 14956535
TI  - [The problem of mixed injections].

PMID- 14956537
TI  - [Not Available].

PMID- 14956536
TI  - [Neurinoma of the intestinal tract occult bleeding].

PMID- 14956538
TI  - [Not Available].

PMID- 14956539
TI  - [Obesity in puberty (adiposogigantism)].

PMID- 14956540
TI  - [Strabismus and its therapy].

PMID- 14956541
TI  - [Diurnal changes in the electrocardiogram].

PMID- 14956542
TI  - [Investigations on the so-called achromoreticulocytes].

PMID- 14956543
TI  - [Observations and investigations on the etiology and pathogenesis of habitual
      aphthous stomatitis].

PMID- 14956544
TI  - [Damage of the gonads by osteoarticular tuberculosis; effects of thorium X on
      spermiogenesis].

PMID- 14956545
TI  - [Results of peteosthor therapy in Bechterew's disease].

PMID- 14956546
TI  - [Improvement of infiltration and block anesthesia by addition of hyaluronidase].

PMID- 14956547
TI  - [Therapeutic problems in the use of adrenal cortical hormones in malnourished
      patients with vegetative disorders].

PMID- 14956549
TI  - [Not Available].

PMID- 14956548
TI  - [Schiller's tuberculosis].

PMID- 14956550
TI  - [Not Available].

PMID- 14956551
TI  - [History of modern thoracic surgery and its role in medicine].

PMID- 14956552
TI  - [Clinical importance and etiology of blood sludge].

PMID- 14956553
TI  - [Areflexia and peripheral vascular disease; therapeutic effects of hydergin].

PMID- 14956554
TI  - [Experiences with the quantitative thymol test in liver diseases].

PMID- 14956555
TI  - [Differential diagnosis: urination disorders].

PMID- 14956556
TI  - [Therapy of salvarsan dermatitis].

PMID- 14956557
TI  - [Oral strophanthin therapy].

PMID- 14956558
TI  - [Experiences with frenantol in hyperthyroidism].

PMID- 14956559
TI  - [Berlin Medical Society].

PMID- 14956560
TI  - [History of modern thoracic surgery; its role in medicine].

PMID- 14956561
TI  - [Diagnosis and therapy of Ewing sarcoma].

PMID- 14956562
TI  - [Late sequellae after arterial injuries].

PMID- 14956563
TI  - [Diagnosis and therapy of malignant pleural neoplasms].

PMID- 14956564
TI  - [Terminal blood stream and venous decompensation].

PMID- 14956565
TI  - [Complications of general anesthesia in thoracic surgery].

PMID- 14956566
TI  - [Differential diagnosis of the predominant bone diseases. V..].

PMID- 14956567
TI  - [Differential diagnosis of peripheral vascular diseases].

PMID- 14956568
TI  - [Resection of large intestines in one session].

PMID- 14956569
TI  - [Therapeutic use of curare in peripheral vascular diseases and ulcers of the
      lower leg].

PMID- 14956570
TI  - [Modern plastic breast surgery].

PMID- 14956571
TI  - [Chlorophyll in therapy of wounds infected with E. coli].

PMID- 14956572
TI  - [38. meeting of the Northwest-German Society for Internal Medicine in Hamburg
      Altona].

PMID- 14956573
TI  - [Evaluation of nutritional value of food substances].

PMID- 14956574
TI  - [Erythrophagic megalosplenism].

PMID- 14956575
TI  - [Compensated and decompensated hyperthyroidism; relation to Selye's general
      adaptation syndrome].

PMID- 14956576
TI  - [Vasal function in the vegetative nervous system as basis for neural therapy].

PMID- 14956577
TI  - [Diagnosis and differential diagnosis of expanding spinal processes].

PMID- 14956578
TI  - [Cerebral swelling and edema complicating diagnostic and therapeutic measures in
      internal medicine].

PMID- 14956579
TI  - [Prophylaxis of struma in children; investigations on 45,818 school children in
      different counties of southern Bavaria].

PMID- 14956580
TI  - [Results of electrophoretic separation of proteins in blood, urine and spinal
      fluid in a plasmocytoma].

PMID- 14956581
TI  - [Differential diagnosis of rheumatoid joint diseases].

PMID- 14956582
TI  - [Pharmacological therapy of arteriosclerosis].

PMID- 14956583
TI  - [Clinical report on dromoran Roche; analgetic compound Ro 1-5431].

PMID- 14956584
TI  - [Therapeutic use of penicillin and intravenous application of liver extracts in
      pernicious anemia].

PMID- 14956585
TI  - [Therapy of varicose veins with a new anticongestive therapy].

PMID- 14956586
TI  - [Experiences with convallan liquidum].

PMID- 14956587
TI  - [Not Available].

PMID- 14956588
TI  - [Viewpoints to determine the nutritional value of food].

PMID- 14956589
TI  - [Psychosomatic evaluation of patients with brain injuries].

PMID- 14956590
TI  - [Etiology of the cascade type stomach].

PMID- 14956591
TI  - [Acceleration of maturation and tonsillar hypertrophy; tonsillar biology in
      relation to age].

PMID- 14956592
TI  - [A clinically diagnosed case of pulmonary or pleural hemangioma].

PMID- 14956593
TI  - [Differential diagnosis: lid abscess or orbital cellulitis].

PMID- 14956594
TI  - [Therapy of liver- and gall bladder diseases].

PMID- 14956595
TI  - [Combined thoracoscopic vago- and sympathicotomy in duodenal ulcer].

PMID- 14956597
TI  - [Berlin Medical Society].

PMID- 14956596
TI  - [Conservative therapy of cryptorchism].

PMID- 14956598
TI  - [Working session of the German Society for Occupational Safety in
      Frankfurt/Main].

PMID- 14956599
TI  - [Biology and pathology of development].

PMID- 14956600
TI  - [Embryopathia rubeolosa].

PMID- 14956601
TI  - [Trauma and tuberculosis].

PMID- 14956602
TI  - [Differential diagnosis of acute pancreas necrosis].

PMID- 14956603
TI  - [Clinical experiences with a new surface anesthetic in dermatology].

PMID- 14956604
TI  - [Circulatory investigations with effortil, cardiazol, coramin and luminal in the
      range of the vita maxima].

PMID- 14956605
TI  - [Experiences with gastro-sil and gastro-sil B in the therapy of gastroduodenal
      diseases].

PMID- 14956606
TI  - [Report from Canada].

PMID- 14956607
TI  - [Not Available].

PMID- 14956608
TI  - [Kiel Medical Society].

PMID- 14956609
TI  - [Arthrosis].

PMID- 14956610
TI  - [Cardiac arrest and resuscitation].

PMID- 14956611
TI  - [Diagnostic importance of temperature graph in neoplastic diseases].

PMID- 14956612
TI  - [Medical poisoning with extractum filicis maris ethereum].

PMID- 14956613
TI  - [Differential diagnosis: schizophrenia and neurosis].

PMID- 14956614
TI  - [Prostate surgery and artificial hypotension].

PMID- 14956615
TI  - [The effects of low intensity diathermy on gynecological diseases].

PMID- 14956616
TI  - [Causal therapy: antireticulocytotoxic serum of Bogomolets].

PMID- 14956617
TI  - [Retrospect on a working session of employed physicians in Koln].

PMID- 14956618
TI  - [Kiel Medical Society].

PMID- 14956619
TI  - [Effects and therapeutic use of cortisone].

PMID- 14956620
TI  - [Primary inertia].

PMID- 14956621
TI  - [The problem of typhus relapse; Brill's disease].

PMID- 14956622
TI  - [Duodenal diverticulum, an etiologic factor of several upper abdominal diseases
      and diabetes mellitus].

PMID- 14956623
TI  - [Experimental investigations on carbohydrate content of the myocardium after
      peroral application of several carbohydrates].

PMID- 14956624
TI  - [Differential diagnosis of hematuria].

PMID- 14956625
TI  - [Letal saponin poisoning by ingestion of horse chestnuts].

PMID- 14956626
TI  - [A new method to decrease pathologically increased muscle tonus].

PMID- 14956627
TI  - [Additional experiences in prophylaxia and therapy of thrombosis and embolism].

PMID- 14956629
TI  - [Diagnosis of neoplastic diseases by copper chloride crystallization method].

PMID- 14956628
TI  - [Therapy of angina pectoris].

PMID- 14956630
TI  - [Kiel Medical Society].

PMID- 14956631
TI  - [Pathogenesis of edema].

PMID- 14956632
TI  - [Pneumoconiosis in cleaners of ship boilers].

PMID- 14956633
TI  - [Change of resistance of bacteria during antibiotic therapy].

PMID- 14956634
TI  - [Cliradon addiction].

PMID- 14956635
TI  - [Differential diagnosis and therapy of depressions].

PMID- 14956636
TI  - [Preoperative medication of hyperthyroidism with scopodystal; therapy of
      vegetative disorders].

PMID- 14956638
TI  - [Therapy of otogenic and rhinogenic pneumococcal meningitis].

PMID- 14956637
TI  - [Possibilities of a combined sulfonamide-hexamethylenetetramine therapy of
      infections of the lower urinary tract].

PMID- 14956639
TI  - [Role of cyclomicrons in pathogenesis of arteriosclerosis; effects of magnesium
      oleate on them].

PMID- 14956640
TI  - [Berlin Medical Society].

PMID- 14956641
TI  - [Bronchiogenic carcinoma; functional pre- and postoperative characterization of
      typical cases of bronchiogenic carcinoma with regard to the situation of the left
      and right heart].

PMID- 14956642
TI  - [Etiology and prophylaxis of puerperal mastitis].

PMID- 14956643
TI  - [Concentrations of paraaminosalicylic acid in the blood serum and urine in
      different ways of application].

PMID- 14956644
TI  - [Differential diagnosis and therapy of external eye diseases].

PMID- 14956645
TI  - [Experiences with blood preserves].

PMID- 14956646
TI  - [Therapeutic results with the Bayer preparation dibutil in parkinsonism].

PMID- 14956648
TI  - [Privy Councillor Professor Ludwig Seitz 80 years old].

PMID- 14956647
TI  - [An attempt to avoid postoperative abdominal adhesions].

PMID- 14956650
TI  - [69. meeting of the German Surgery Society in Munchen].

PMID- 14956649
TI  - [Toxic effects of streptomycin on the hemopoietic system].

PMID- 14956651
TI  - [Problems of care of diabetic patients; critical comment on the differential
      diagnosis of glucosurias and on the evaluation of metabolic status of the
      diabetic patient].

PMID- 14956652
TI  - [Poisoning by ortho-tricresylphosphate; special reference to the cutaneous
      application].

PMID- 14956653
TI  - [Cardiac dynamics in endocarditis and development of final valvular lesion].

PMID- 14956654
TI  - [Prophylaxis of letal complications in myocardial infarct].

PMID- 14956655
TI  - [Carotis sinus reflexes in essential hypertension].

PMID- 14956656
TI  - [Dynamics of blood coagulation. I. Counter regulation of the organism after
      liberation of thrombokinase].

PMID- 14956657
TI  - [Experimental investigation on the effects of certain humic acids of the mud in
      the therapy of rheumatic diseases].

PMID- 14956658
TI  - [New viewpoints in the oral therapy of penicious anemia with vitamin B12].

PMID- 14956659
TI  - [Effects of central and peripheral circulatory stimulants after application of
      muscle relaxant My 301].

PMID- 14956660
TI  - [Experiences in therapy of chronic rheumatic diseases with nitrogen mustard].

PMID- 14956661
TI  - [Therapeutic effects of sulfonamides and antibiotics on destruction products of
      coli bacteria].

PMID- 14956662
TI  - [Diagnosis of toxoplasmosis by bioptic demonstration of the parasites in skin
      lesions].

PMID- 14956663
TI  - [The German literature on plague in the 15th century].

PMID- 14956664
TI  - [Circle of inhibition and circle of progression in pathogenesis and therapy of
      stuttering].

PMID- 14956665
TI  - Change with age in susceptibility to minor respiratory illness.

PMID- 14956666
TI  - Incidence of pneumonia in two communities in New York State.

PMID- 14956667
TI  - Social and psychological factors affecting fertility. XVII. The interrelation of
      fertility, fertility planning, and feeling of personal inadequacy.

PMID- 14956668
TI  - Anticipated progress of sylvan yellow fever in Nicaragua: plan for attempt to
      block its course in Honduras.

PMID- 14956669
TI  - Pneumoarthrography of the knee.

PMID- 14956670
TI  - Solitary renal cyst (case report).

PMID- 14956671
TI  - Local use of antibiotics in chronic urethritis.

PMID- 14956672
TI  - Massive parotid gland tumor.

PMID- 14956673
TI  - Foot-and-mouth disease in Western Germany during 1951.

PMID- 14956674
TI  - A neglected blinder.

PMID- 14956676
TI  - EXTENSION of veteran benefits.

PMID- 14956675
TI  - Shoulder straps for Aesculapius.

PMID- 14956677
TI  - PROMOTION for Dr. Shaw.

PMID- 14956678
TI  - INCREASES in compensation.

PMID- 14956679
TI  - Major General Merritte W. Ireland, U.S. Army, ret.

PMID- 14956680
TI  - [Diaphragmatic hernia of the liver].

PMID- 14956681
TI  - [Effect of tetrahydro-furfuryl ester of nicotinic acid (Trafuril) in the therapy
      of peripheral arteriopathy].

PMID- 14956682
TI  - [Clinical research on a new synthetic analgesic preparation (Prep. 7115-Cliradon
      Ciba)].

PMID- 14956683
TI  - [Etiopathogenetic basis for a rational therapy of acute hemorrhagic conditions].

PMID- 14956684
TI  - [A case of sub-cutaneous presternal cystic goiter].

PMID- 14956685
TI  - [A rare case of cysts caused by echinococcus multilocularis of the iliac bone].

PMID- 14956686
TI  - [Pseudo-neoplastic hypertrophic tuberculosis of the anus].

PMID- 14956687
TI  - [Experimental research by the Lecompte du Nouy method on variations induced by
      para-amino-salicylic acid, streptomycin and penicillin on the healing of surgical
      wounds].

PMID- 14956688
TI  - [Trauma and orchiepididymitis; experimental note].

PMID- 14956689
TI  - [Pneumo-cisternographic findings in optic-chiasmatic arachnoiditis].

PMID- 14956690
TI  - [Transposition of the vagus nerves in a thoracic operation for diaphragmatic
      hernia of the esophageal hiatus].

PMID- 14956691
TI  - [Electrocardiograph changes in pulmonary tuberculosis after surgical
      collapsotherapy].

PMID- 14956692
TI  - [Anatomical notes and anatomo-surgical remarks concerning the thyroid].

PMID- 14956693
TI  - [Azotemic titers in about 700 subjects treated surgically for various
      affections].

PMID- 14956694
TI  - [Stenosis of the cardia and esophageal achalasia; a case treated with total
      cardioplasty].

PMID- 14956695
TI  - [A case of carcinoma of the small intestine].

PMID- 14956696
TI  - [Surgical treatment of 20 cases of goiter; clinical and therapeutic study].

PMID- 14956697
TI  - [Three cases of rib fracture from coughing].

PMID- 14956698
TI  - [Marco Aurelio Severino: reviver of Italian surgery].

PMID- 14956699
TI  - [Fifth meeting of the Societa Siciliana di Chirurgia].

PMID- 14956700
TI  - [Sarcoma of the esophagus].

PMID- 14956701
TI  - [Eight total cystectomies with ureterosigmoidostomy performed according to a
      modified Wattenberg-Beare method].

PMID- 14956702
TI  - [Etiopathogenesis and rational therapy in surgery; traumatic shock and related
      conditions].

PMID- 14956703
TI  - [High resection of the upper thoracic esophagus and reconstruction with plastic
      tubes; experimental study].

PMID- 14956704
TI  - [High resection of the thoracic esophagus and reconstruction with fresh
      homologous graft and fixed graft; experimental study].

PMID- 14956705
TI  - [Inter-regional pediatric and surgical convention on tumors in children].

PMID- 14956706
TI  - [First Eritrean Interregional Medical Congress].

PMID- 14956707
TI  - [Exceptional pathogenesis of gastrorrhagia in old resection of the stomach;
      rupture of the duodenal stump by aneurism of the gastroduodenal artery].

PMID- 14956708
TI  - [Azotemic titers in about 400 subjects hospitalized for various diseases].

PMID- 14956709
TI  - [Surgery of the biliary tract; study of about 500 cases].

PMID- 14956710
TI  - [Early metastasis of primary pulmonary tumor to the patella].

PMID- 14956711
TI  - [Destruction of the lower part of the nose by lupus; reconstruction with
      abdominal tube].

PMID- 14956712
TI  - [Preoperative reduction of the intestinal flora with streptomycin-sulfamide
      vitamin preparation in surgery of the large intestine].

PMID- 14956713
TI  - [Tracheal intubation in local anesthesia of the pharyngo-laryngo-tracheal
      surface].

PMID- 14956714
TI  - [Oscillations of the lumbodorsal spine; diagnostic use].

PMID- 14956715
TI  - [Resections of the esophagus].

PMID- 14956716
TI  - [Eighth Congress of the International College of Surgeons; Madrid 20-24 May
      1952].

PMID- 14956717
TI  - [Artificial jugular-carotid anastomosis in therapy of cerebral spastic infantile
      paralysis].

PMID- 14956718
TI  - [Behavior of the blood sugar curve after prefrontal leukotomy].

PMID- 14956720
TI  - [Pseudodiverticular adenocarcinoma of the esophagus].

PMID- 14956719
TI  - [Behavior of gastric function after prefrontal leukotomy].

PMID- 14956721
TI  - [Therapy of the so-called sarcomas of the soft parts with particular reference to
      myectopy for primary sarcomas of the muscles].

PMID- 14956722
TI  - [Cecal fibroma arising on invaginated appendix stump].

PMID- 14956723
TI  - [Therapy of massive acute hemorrhage caused by gastroduodenal ulcer].

PMID- 14956724
TI  - [Constitution of the periesophageal vagus nerves].

PMID- 14956725
TI  - [Dolantin, adjuvant analgesic in general anesthesia].

PMID- 14956726
TI  - [Evolution and therapy of functional gastro-jejunal syndromes secondary to
      gastric resection].

PMID- 14956727
TI  - [Cutaneous manifestations of berylliosis].

PMID- 14956728
TI  - [Blood proteins in pemphigus; electrophoretic study].

PMID- 14956729
TI  - [Behavior of leukocytic lipids in blennorrhagic subjects].

PMID- 14956730
TI  - [The presence of the "sign of Bizzozero" in the papular and nodular form of basal
      cell epithelioma].

PMID- 14956731
TI  - [Attempted therapy for lupus vulgaris and juvenile acne with provitamins of the D
      group].

PMID- 14956732
TI  - [Aureomycin in non-gonococcic urethritis].

PMID- 14956733
TI  - [Anti-venereal service in preventive and penal institutions].

PMID- 14956734
TI  - [Sulfone and phagocytic ability; experimental research].

PMID- 14956735
TI  - [Nevose heterotopia of the apocrine glands with mucous degeneration of the
      connective tissue and blood vessel changes].

PMID- 14956736
TI  - [Cutaneous lesions in man caused by virus of infectious pustular stomatitis of
      sheep].

PMID- 14956737
TI  - [Clinical and statistical study of 76 cases of arsenobenzolic erythroderma cured
      in the Clinic during the period 1932-51].

PMID- 14956738
TI  - [Behavior of the urinary 17-ketosteroids and blood eosinophils in caustic burns].

PMID- 14956739
TI  - [Blood protein disorders in pregnancy; essential edema and non-hypertensive
      nephropathy].

PMID- 14956740
TI  - [Hydroviscous media in hysterosalpingography].

PMID- 14956741
TI  - [Intrauterine instillation of adrenalin in some dysfunctional metrorrhagias].

PMID- 14956742
TI  - [Action of protamine sulfate of the heparin-like substance of follicular fluid].

PMID- 14956743
TI  - [Heparin tolerance test in vitro and the menstrual cycle].

PMID- 14956744
TI  - [Urinary elimination of 17-ketosteroids during and after roentgen castration].

PMID- 14956745
TI  - [Use of curare as an anesthetic and oxytocic in labor].

PMID- 14956746
TI  - [Anterolateral cordotomy (spinothalamic tractotomy) in pain syndromes of
      incurable uterine cancer].

PMID- 14956747
TI  - [Leiomyoma of the fallopian tube].

PMID- 14956748
TI  - [Effect of nicotinic hexa-ester of m-inosite (Exantene) in menopausal
      hypertension].

PMID- 14956749
TI  - [Urological aspects in uterine fibromas before and after hysterectomy].

PMID- 14956750
TI  - [Endocrine action of paraoxypropiophenone].

PMID- 14956751
TI  - [The heparin co-factor (serum albumin X) in puerperium].

PMID- 14956752
TI  - [Contraindications for estrogen therapy in chorionepithelioma].

PMID- 14956753
TI  - [Procedure for extraction, separation and purification of the 17-ketosteroids and
      estrogenic phenolsteroids from the urine of the equine and bovine species].

PMID- 14956754
TI  - [A case of purulent arthritis in newborn infant].

PMID- 14956755
TI  - [Premarital eugenics].

PMID- 14956756
TI  - [Vulvar pruritus therapy].

PMID- 14956757
TI  - [The great luminous figure of Guido Baccelli (1832-1916)].

PMID- 14956758
TI  - [Moliere and the Court physicians].

PMID- 14956759
TI  - [The physician's legal responsibility for prescription errors].

PMID- 14956760
TI  - [Tetracetin in the prophylaxis and therapy of otorhinolaryngologic affections].

PMID- 14956761
TI  - [Results of streptomycin therapy in a mountain sanatorium].

PMID- 14956762
TI  - [Method of administration of cortisone and cortisone simulants in chronic joint
      diseases].

PMID- 14956763
TI  - [The thumbs as opposed to the palms of the Shroud of Turin].

PMID- 14956764
TI  - [Constitution of the Piedmontese Section of the Italian Hygiene Association].

PMID- 14956765
TI  - [Three-branched angiostat for latero-lateral anastomosis between the aorta and
      pulmonary artery].

PMID- 14956766
TI  - [Retroperitoneal insufflation for radiological examination of children].

PMID- 14956767
TI  - [Retroperitoneal insufflation for radiological examination of children].

PMID- 14956768
TI  - [Clinical and statistical review of the therapeutic property of calendula
      officinalis (Helicrysum Italicum)].

PMID- 14956769
TI  - [An "acute abdomen"].

PMID- 14956770
TI  - [Penicillin: return of sovereignty].

PMID- 14956771
TI  - [World Health Day and the Fourth Anniversary of the World Health Organization].

PMID- 14956772
TI  - [Chemical changes in the nerve cells and their relation to function and age].

PMID- 14956773
TI  - [The physiological mechanism of sleep].

PMID- 14956774
TI  - [Cerebral conditions in delirium].

PMID- 14956775
TI  - [Current therapy of myasthenia].

PMID- 14956776
TI  - [Bal therapy of encephalitis caused by thallium].

PMID- 14956777
TI  - [Recent contributions to the anatomy and pathology of the hypothalamus].

PMID- 14956778
TI  - [Cerebral electro-stimulation with direct current (human electronarcosis with
      alpha-wave current) I. Neurological and functional phenomenology].

PMID- 14956779
TI  - [Cerebral electro-stimulation with direct current (human electronarcosis with
      alpha-wave current). II. Therapeutic effects].

PMID- 14956780
TI  - [Histamine in psychiatric therapy].

PMID- 14956781
TI  - [Recording of displacements of the corneo-retinal dipole in the study of
      nystagmus and of ocular movements in general].

PMID- 14956782
TI  - [Diagnostic significance of pyography in otogenic suppurative encephalitis].

PMID- 14956783
TI  - [Two cases of dystonia of motion of the lower limbs].

PMID- 14956784
TI  - [Blood chemistry in relation to electronarcosis (EN)].

PMID- 14956785
TI  - [Blood chemistry in relation to Filatov's tissue therapy (TTF) in some grave
      neurological and psychiatric syndromes].

PMID- 14956786
TI  - [Blood chemistry in relation to narcosis and subnarcosis caused by barbiturates
      of brief and rapid action].

PMID- 14956787
TI  - [A case of "difficulty in walking symptomatic of a state of unknown
      disequilibrium" described by Barre].

PMID- 14956788
TI  - [So-called post-influenzal psychoses].

PMID- 14956789
TI  - [Attempted therapy of some mental diseases by Filatov method].

PMID- 14956790
TI  - [Cutaneous hemorrhage (hematohidrosis) and fever of psychogenic origin;
      pathogenetic mechanism].

PMID- 14956791
TI  - [Treatment of sleep rhythm inversion].

PMID- 14956792
TI  - [Tissue therapy with electroshocked brain].

PMID- 14956793
TI  - [Experimental research on the effect of roentgen rays on regeneration and
      cicatricial phenomena of peripheral nerves in lesions caused by crushing].

PMID- 14956794
TI  - [Moral judgment test (tsedek of Baruk)].

PMID- 14956795
TI  - [Insulin coma induced by reduced doses of insulin combined with hyaluronidase].

PMID- 14956796
TI  - [Effect of intravenous procaine on experimental pyrexia induced in man].

PMID- 14956797
TI  - [Prolonged electronarcosis].

PMID- 14956798
TI  - [Constituent Assembly of the Mediterranean Medical Union].

PMID- 14956799
TI  - [For the pension of all hospital physicians].

PMID- 14956800
TI  - [Parish doctors and hospital doctors].

PMID- 14956801
TI  - [So-called congenital varices of the esophagus; a case of resection in multiple
      telangiectasis of the thoracic esophagus].

PMID- 14956802
TI  - [Menstrual cycle and infectious diseases].

PMID- 14956803
TI  - [New orientation in therapy of female climacteric disturbances].

PMID- 14956804
TI  - [New American drugs of 1951].

PMID- 14956805
TI  - [Symposium on cortisone].

PMID- 14956806
TI  - [Centennial celebration for Guido Banti at the Mauriziana Hospital in Turin].

PMID- 14956807
TI  - [The contribution of Guido Banti to medical education and research].

PMID- 14956808
TI  - [Modernness of Banti's ideas concerning leukemia].

PMID- 14956809
TI  - [Blood changes in Banti's disease].

PMID- 14956810
TI  - [Portal obstructions].

PMID- 14956811
TI  - [Banti's disease; contribution to casuistics].

PMID- 14956812
TI  - [Gastrorrhagic splenomegaly caused by portal hypoplasia].

PMID- 14956813
TI  - [Bacteriological warfare in Korea].

PMID- 14956814
TI  - [University education in England].

PMID- 14956815
TI  - [Second International Congress of Thermal Medicine and Climatothalassotherapy].

PMID- 14956816
TI  - [Anti-edematigenous effect of cation exchange resins on rheumatics treated with
      cortisone; preventive note].

PMID- 14956817
TI  - [Local injection of antibiotics in treatment of localized infections].

PMID- 14956818
TI  - [Relation between O-antistreptolysin and gamma globulin].

PMID- 14956819
TI  - [Complications caused by pulmonary exeresis in tuberculosis].

PMID- 14956820
TI  - [International Congress on Gerontology and Geriatrics].

PMID- 14956821
TI  - [Poisoning from synthetic plant insecticides].

PMID- 14956822
TI  - [Remote anatomical results of streptomycin therapy in miliary tuberculosis of the
      lung].

PMID- 14956823
TI  - [Reflections on the progress of medical science and responsibility for the
      future].

PMID- 14956824
TI  - [Salicylic therapy of chronic colitis].

PMID- 14956825
TI  - [The importance of theoretic hematology].

PMID- 14956826
TI  - [Pathogenesis of the so-called "seashore tuberculosis" hyperergia from sun rays].

PMID- 14956827
TI  - [Natural and decaffeinized coffee on the cardiovascular system].

PMID- 14956828
TI  - [Immunization of the human organism to the Rh factor].

PMID- 14956829
TI  - [Absorption of medicaments in suppositories].

PMID- 14956830
TI  - [The International Jubilee Congress of the Societa Francese di Ginecologia].

PMID- 14956831
TI  - [Alfredo Jachia and the beginning of thoracic surgery in Italy].

PMID- 14956832
TI  - [The treatment of caverns].

PMID- 14956833
TI  - [The problem of hilo-basal caverns].

PMID- 14956834
TI  - [Health service after six years of medical and surgical treatment of phthisis].

PMID- 14956835
TI  - [Therapeutic action of antibiotics in tuberculosis].

PMID- 14956836
TI  - [Advantage of smoking in disturbances caused by nicotinic abstinence on the part
      of a subject with pneumothorax].

PMID- 14956837
TI  - [Contralateral pneumothorax during artificial pneumothorax].

PMID- 14956838
TI  - [Arthropathy and pleuralgia consensual with tumoral disease].

PMID- 14956839
TI  - [Clinical and statistical study of pleurisy in patients hospitalized in the last
      decade].

PMID- 14956840
TI  - [Have antibiotics changed the duration of therapeutic pneumothorax?].

PMID- 14956841
TI  - [Latent pulmonary tuberculosis activated by thermal factors].

PMID- 14956842
TI  - [Award of the "La Presse Medicale" prize for the best medico-scientific film].

PMID- 14956843
TI  - [Cecilio Folli of Fanano, anatomist of the seventeenth century].

PMID- 14956844
TI  - [Interregional Pediatric-Surgical Conference on tumors in children].

PMID- 14956845
TI  - [Reanimation with intra-carotid transfusion in cranial direction; documentary
      film].

PMID- 14956847
TI  - [General aspects of psychosomatic medicine].

PMID- 14956846
TI  - [Vaso-active arterial effects of some sympathicomimetic drugs and acetylcholine].

PMID- 14956849
TI  - [Opening of the new quarters of the Blalock Center of Cardiosurgery at the
      Surgical Clinic of the University of Turin].

PMID- 14956848
TI  - [Artificial feeding of newborn infants].

PMID- 14956850
TI  - [Diabetic disease].

PMID- 14956851
TI  - [Treatment of infantile encephalopathy].

PMID- 14956852
TI  - [Treatment of epidemic parotitis with paraminobenzoic acid, aureomycin,
      chloramphenicol and terramycin].

PMID- 14956853
TI  - [The use of therapeutic aerosols in gynecology].

PMID- 14956854
TI  - [Antonio Frassoni, professor of Francesco Torti].

PMID- 14956855
TI  - [Medico-legal diagnosis of drunkenness in street incidents].

PMID- 14956856
TI  - [Study of dynamic-specific action with the intravenous use of amino acids].

PMID- 14956857
TI  - [Variations of the blood protein picture and of some liver function tests in
      liver diseases after prolonged administration of pantothenic acid].

PMID- 14956858
TI  - [Tetralogy and trilogy of Fallot; differential diagnosis and operative
      indications].

PMID- 14956859
TI  - [Lipo-fibro-calcareous myopathy].

PMID- 14956860
TI  - [The contribution of x-ray investigation in the study of lipo-fibro-calcareous
      myopathy].

PMID- 14956861
TI  - [A visit to the isotope laboratory of the Necker Hospital for children in Paris].

PMID- 14956862
TI  - [Differential diagnosis of transudates and exudates in clinical practice].

PMID- 14956863
TI  - [Analysis of the electrophoretic spectrum of serum; a case of dysprotidemia in
      the course of systemic anaplasia of reticular tissue].

PMID- 14956864
TI  - [Blood colloid changes in favism].

PMID- 14956865
TI  - [X-ray documents on the spasmolytic action of Lyspamin in hypertonic dystonia of
      the colon].

PMID- 14956866
TI  - [Evidence of disease previously unknown in ancient Egypt].

PMID- 14956867
TI  - [Therapeutic action of the pancreatic anti-steatosis factor in psoriasis].

PMID- 14956868
TI  - [Antityphoid therapy with chloramphenicol; evaluation after two years of
      experimental use].

PMID- 14956869
TI  - [B.A.L. in intoxication by bisulphate of quinine].

PMID- 14956870
TI  - [Local treatment of versicolor pityriasis with penicillin].

PMID- 14956871
TI  - [Treatment of fibrocystic mastopathy].

PMID- 14956872
TI  - [Professional life in Great Britain].

PMID- 14956873
TI  - [First Congress on Medical Gymnastics].

PMID- 14956874
TI  - [Medical and social aspects of constipation].

PMID- 14956875
TI  - [Effect of ultrasonics on gastric chemistry].

PMID- 14956876
TI  - [Connections between bronchial arterial circulation and the functional
      circulation of the lung].

PMID- 14956877
TI  - [Antibiotic action of vitamin C on Koch's bacillus].

PMID- 14956878
TI  - [Possible harmful effects of penicillin prolonging solvents].

PMID- 14956879
TI  - [Importance of medical history studies].

PMID- 14956880
TI  - [The throne of Venus or a childbirth scene in Greek art].

PMID- 14956881
TI  - [Marine serum, concept of its inventor, Rene Quinton; possibility of its
      application today].

PMID- 14956882
TI  - [Moxa].

PMID- 14956883
TI  - [Combined adrenalin and penicillin in experimental staphylococcic septicemia].

PMID- 14956884
TI  - [Research on protein fractions and protein-bound polysaccharides in the blood of
      the aged].

PMID- 14956885
TI  - [Behavior of venous pressure after intraarterial and intravenous transfusions].

PMID- 14956886
TI  - [Streptomycin treatment of tubercular adolescents (clinical and statistical
      results].

PMID- 14956887
TI  - [Aerosol vaccination with BCG].

PMID- 14956888
TI  - [Fifteenth National Antituberculosis Campaign].

PMID- 14956889
TI  - [First clinical report on therapeutic use of isonicotinic acid hydrazide in human
      tuberculosis].

PMID- 14956890
TI  - [Antitubercular properties of isonicotinic acid hydrazide].

PMID- 14956891
TI  - [First clinical results of treatment of 50 cases of pulmonary tuberculosis with
      isonicotinic acid hydrazide].

PMID- 14956892
TI  - [First clinico-radiological report on the effect of isonicotinic acid hydrazide
      in pulmonary tuberculosis].

PMID- 14956893
TI  - [Isonicotinic acid hydrazide therapy of pulmonary tuberculosis].

PMID- 14956894
TI  - [Use of isonicotinic acid hydrazide in collapse therapy and exeresis in pulmonary
      tuberculosis].

PMID- 14956895
TI  - [Effect of isonicotinic acid hydrazide in tubercular laryngitis and bronchitis].

PMID- 14956896
TI  - [Chemotherapy of tuberculosis: isonicotinic acid hydrazide and combined chemical
      and antibiotic therapy of experimental ocular tuberculosis].

PMID- 14956897
TI  - [First anatomo-pathological report on the effect of isonicotinic acid hydrazide
      in experimental tuberculosis in guinea pigs].

PMID- 14956898
TI  - [A case of acute miliary tuberculosis treated with isonicotinic acid hydrazide].

PMID- 14956899
TI  - [Complications and incidents in isonicotinic acid hydrazide therapy of pulmonary
      tuberculosis].

PMID- 14956900
TI  - [Laboratory data on several tubercular subjects during isonicotinic acid
      hydrazide therapy].

PMID- 14956901
TI  - [Method of determination of isonicotinic acid hydrazide in urine].

PMID- 14956902
TI  - [First clinical tests of isonicotinic acid hydrazide in the Sanatoria of the
      Piedmont].

PMID- 14956903
TI  - [Isonicotinic acid hydrazide in antitubercular therapy abroad].

PMID- 14956904
TI  - [Opinion of Italian clinicians and phthisiologists concerning the therapeutic
      uses of isonicotinic acid hydrazide].

PMID- 14956905
TI  - [Professor Giovanni Battista Alleria].

PMID- 14956906
TI  - [Defense of breast feeding in Spain].

PMID- 14956907
TI  - [Treatment of hypogalactia with vitamin PP].

PMID- 14956908
TI  - [Hypertrophic stenosis of the pylorus].

PMID- 14956909
TI  - [Serious case of diaphragm relaxation in newborn infant].

PMID- 14956910
TI  - [Clinical methodology in nepiology].

PMID- 14956911
TI  - [International meetings of pediatricians].

PMID- 14956912
TI  - [Acute encephalitis in children].

PMID- 14956913
TI  - Sickle cell anemia in Greece.

PMID- 14956914
TI  - Prophylaxis of cerebral palsy.

PMID- 14956915
TI  - [Hydrocarbon metabolism disorders in dystrophia].

PMID- 14956916
TI  - [New horizons in child health].

PMID- 14956917
TI  - [Physiopathology of immunity in children].

PMID- 14956918
TI  - [Some problems of endocrinology in pediatrics].

PMID- 14956919
TI  - [The task of the pediatrician in the psycho-pedagogy of the difficult child].

PMID- 14956920
TI  - [Congenital megacolon].

PMID- 14956921
TI  - [Congenital atresia of the esophagus].

PMID- 14956922
TI  - [Evolution of periarteritis nodosa (polyarteritis) in infancy; a clinical case].

PMID- 14956923
TI  - [Ten cases of cutaneous primary complex tuberculosis].

PMID- 14956924
TI  - [Several cases of cerebral hemorrhage in newborn infants].

PMID- 14956925
TI  - [Titer of antistreptolysin in the fetus, newborn premature and at term, and
      infant during the first months of life; relations between titers of newborn
      infant and mother].

PMID- 14956926
TI  - [Chloramphenicol therapy and shock].

PMID- 14956927
TI  - [Tolerance tests of vitamin A (oral and intramuscular) in normal infants].

PMID- 14956928
TI  - [A case of congenital extrinsic intestinal occlusion; complete subraterian
      stenosis due to mesenterium commune].

PMID- 14956929
TI  - [Research on absorption and elimination of TB-1-698 in children].

PMID- 14956930
TI  - [Effect of penicillin and streptomycin on blood coagulation].

PMID- 14956931
TI  - [Behavior of anti-typhoid agglutinins in chloramphenicol, treatments].

PMID- 14956932
TI  - [Behavior of the blood protein picture in tuberculosis in children].

PMID- 14956933
TI  - [Tests of colloidal lability and the blood protein picture in blood from the
      umbilical cord].

PMID- 14956934
TI  - [Glucose tolerance test curve in mongoloids].

PMID- 14956935
TI  - [Toxic granulations in gastroenteritis in infants].

PMID- 14956936
TI  - [Patch test].

PMID- 14956937
TI  - [Tincture of hedera in whooping cough therapy].

PMID- 14956938
TI  - [Clinical research on a new colloidal lability test].

PMID- 14956939
TI  - [Eduard Glanzmann].

PMID- 14956940
TI  - [Thrombopathy in the hemorrhagic diseases of infancy].

PMID- 14956941
TI  - [Thrombocytic diseases of infancy].

PMID- 14956942
TI  - [Treatment of whooping cough with streptomycin diapneumotherapy in inhalation
      room with pilot device].

PMID- 14956943
TI  - [Transpulmonary administration of chloramphenicol in infancy].

PMID- 14956944
TI  - [The use of powdered carob in dietetic therapy of infants].

PMID- 14956945
TI  - [Willebrand-Jurgens disease].

PMID- 14956946
TI  - [A case of post-scarlatina purpura fulminans with rare postmortem findings of
      conspicuous liver peliosis].

PMID- 14956948
TI  - [Periarteritis nodosa in infancy].

PMID- 14956947
TI  - [Prothrombinemia and intestinal flora in newborn infants].

PMID- 14956949
TI  - [Relapses and recurrences of purulent meningitis].

PMID- 14956950
TI  - [Research on visualization of the hilarmediastinal lymph glands by combined
      posterior pneumomediastinum and stratigraphy].

PMID- 14956951
TI  - [Three years of experience in streptomycin therapy of tubercular meningitis].

PMID- 14956952
TI  - [A case of acute leukemia treated with teropterin and urethane].

PMID- 14956953
TI  - [A case of recurrent chicken pox].

PMID- 14956954
TI  - [Accidental diseases in childhood].

PMID- 14956955
TI  - [Interregional Pediatric-Surgical Conference on tumors in children].

PMID- 14956956
TI  - [National Congress of Obstetricians].

PMID- 14956957
TI  - [Diagnosis of subarachnoid blocks in tubercular leptomeningitis treated with
      streptomycin].

PMID- 14956958
TI  - [Erythrosedimentation time in children affected with tubercular meningitis
      treated with streptomycin].

PMID- 14956959
TI  - [Cardiological notes; the anemic heart].

PMID- 14956960
TI  - [Acute appendicitis in the first years of life].

PMID- 14956961
TI  - [Suboccipital or spinal infection of isonicotinic acid hydrazide in animals and
      humans and first report on the activity of the drug in tubercular meningitis and
      primary pulmonary tuberculosis in children].

PMID- 14956962
TI  - [Pathology of the middle lobe in children].

PMID- 14956963
TI  - [Two cases of Stevens-Johnson syndrome (infectious dermato-stomato
      ophthalmitis)].

PMID- 14956964
TI  - [Sodium nicotinate tolerance test in the study of liver function in the child].

PMID- 14956965
TI  - [Ehlers-Danlos syndrome].

PMID- 14956966
TI  - [On the 60th birthday of Prof. Jakob Wyrsch].

PMID- 14956967
TI  - A case of Ependymoma of the Aquaduct of Sylvius.

PMID- 14956968
TI  - [Investigations on the projection of the thalamus in man].

PMID- 14956969
TI  - [The use of spinal fluid pumps in psychiatry].

PMID- 14956970
TI  - [Thoughts during a high fall; a psychophysical study].

PMID- 14956971
TI  - [Gestational psychoneuroses treated with blood transfusion].

PMID- 14956972
TI  - [Headache in gynecology].

PMID- 14956973
TI  - [Case of essential migraine of endocrine etiology].

PMID- 14956974
TI  - [Typical and atypical histological aspects in tuberculosis of the endometrium].

PMID- 14956975
TI  - [Local use of antibiotics in pelvic cellulitis].

PMID- 14956976
TI  - [Hepatic steatosis of the infant, 155 observations].

PMID- 14956977
TI  - [Study of miliary pulmonary tuberculosis treated by streptomycin].

PMID- 14956978
TI  - [Study of 47 cases of grippe, biologically confirmed by Hirst's reaction,
      observed in children during the winter of 1950-51 in the Montpellier area].

PMID- 14956979
TI  - [Tracings of slow sinusoidal monorhythmia with posterior predominance and meningo
      corticalitis in the course of tuberculous meningitis in children, treated by
      streptomycin].

PMID- 14956980
TI  - [Atypical broncho-pneumonias of children, anatomo-clinical and radiological
      aspects].

PMID- 14956981
TI  - The Cavendish Laboratory Archives.

PMID- 14956982
TI  - SANTIAGO Ramon Y Cajal (1852-1934).

PMID- 14956983
TI  - SIR Charles Sherrington, O.M., G.B.E., F.R.S.

PMID- 14956985
TI  - DR. Konrad Dobriner.

PMID- 14956984
TI  - W. S. Millard.

PMID- 14956986
TI  - Action of snake venom on acetylcholine synthesis in brain.

PMID- 14956987
TI  - BODY temperatures in nestling western gulls.

PMID- 14956988
TI  - A new synthesis of isoflavones.

PMID- 14956989
TI  - Separation of the 3,5-dinitrobenzoates of volatile alcohols by paper
      chromatography.

PMID- 14956990
TI  - Feasibility of quantitative separation of the threo- and erythro-forms of amino
      acids by column chromatography.

PMID- 14956991
TI  - Counter-current distribution of nisins.

PMID- 14956992
TI  - Suggested use of a bismuth mercaptoimidazole compound as a specific colour
      reagent for iodines.

PMID- 14956993
TI  - A new method for the degradation of peptides.

PMID- 14956994
TI  - Coenzyme A as a co-factor of the pyruvate dehydrogenase system of Cl.
      saccharobutyricum.

PMID- 14956995
TI  - Effect of amellin in the prevention of fatty infiltration in the liver.

PMID- 14956996
TI  - Bacterial arylsulphatase.

PMID- 14956997
TI  - Morphine antagonism.

PMID- 14956998
TI  - Total concentration of fixed base in cells of the renal cortex of the rat.

PMID- 14956999
TI  - Preservation of cytological material by storage at or below -10 degrees C.

PMID- 14957000
TI  - Embryo of the coconut.

PMID- 14957001
TI  - Forking in pine roots.

PMID- 14957002
TI  - Effect of adding penicillin to turkey starter mash.

PMID- 14957003
TI  - Ethylene oxide for soil sterilization.

PMID- 14957004
TI  - Myxomatosis in Australia; a step towards the biological control of the rabbit.

PMID- 14957005
TI  - Sir James Irvine, K.B.E., F.R.S.

PMID- 14957006
TI  - COSMETICS and dermatitis.

PMID- 14957007
TI  - Tanning of fatty acid and protein monolayers by metal ions (Cr, Al, Fe and Cu).

PMID- 14957008
TI  - A possible source of artifacts in the chromatography of tissue extracts
      containing inorganic iodide.

PMID- 14957009
TI  - Ionophoretic separation of porphyrin pigments.

PMID- 14957010
TI  - Cellular permeability of yeast to metallic ions.

PMID- 14957011
TI  - Vision with a stabilized retinal image.

PMID- 14957012
TI  - Male sterile plants by chemical treatment.

PMID- 14957013
TI  - Detoxication of hormone herbicides by soil bacteria.

PMID- 14957014
TI  - Supra-vital staining of striated muscle with tetrazolium compounds.

PMID- 14957015
TI  - Noradrenaline and accessory chromaffin tissue.

PMID- 14957016
TI  - Effect of cortisone on the blood pressure of normal rats.

PMID- 14957017
TI  - STRUCTURE of proteins.

PMID- 14957018
TI  - An unusual transformation of isometric forms of tetra acetyl D-ribofuranose.

PMID- 14957019
TI  - Lysenko's latest discovery--the conversion of wheat into rye, barley and oats.

PMID- 14957020
TI  - Selection of the genetic basis for an acquired character.

PMID- 14957021
TI  - Trematode life-cycle enacted in a London pond.

PMID- 14957022
TI  - Moonlight and the pregnancy of Malayan forest rats.

PMID- 14957023
TI  - Environmental temperature and the glycogen content of the frog's liver (Rana
      temporaria).

PMID- 14957024
TI  - Presence of ferritin in a marine elasmobranch. Scyllium canicula.

PMID- 14957025
TI  - A new species of the Mystacocaridea (Crustacea).

PMID- 14957026
TI  - Amino-acids in legumes.

PMID- 14957027
TI  - Serological properties of human blood group A and B substances.

PMID- 14957028
TI  - A relationship between the secretion of the blood group antigens and the presence
      of anti-O or anti-H in human serum.

PMID- 14957029
TI  - Acetylcholine esterase of the white components of blood.

PMID- 14957030
TI  - Retinal colour processes caused by intermittent white light.

PMID- 14957031
TI  - Vitamin A ester and vitamin A alcohol in the serum of the oestrogenized immature
      pullet.

PMID- 14957032
TI  - Absorption from intestine or rats with blind self-filling pouch.

PMID- 14957034
TI  - Adsorption of amino-acids on sparingly soluble inorganic solids.

PMID- 14957033
TI  - Effect of scopoletin on indolacetic acid metabolism.

PMID- 14957035
TI  - Biosynthesis of carotenes in ripening tomatoes.

PMID- 14957036
TI  - Influence of thiourea on reproduction in the minnow.

PMID- 14957037
TI  - Competitive suppression and the determination of linkage in microorganisms.

PMID- 14957038
TI  - International health organizations.

PMID- 14957040
TI  - Calculation of the internal surface of a lung.

PMID- 14957039
TI  - Fine structure of chloroplasts in two flagellates.

PMID- 14957041
TI  - Haemolytic and surface activity of sodium taurocholate.

PMID- 14957042
TI  - Stabilization of oxidative phosphorylation in heart-muscle sarcosomes.

PMID- 14957043
TI  - Glucose-6-phosphate dehydrogenase activity of rat liver.

PMID- 14957044
TI  - Polynucleotides from deoxyribonucleic acids.

PMID- 14957045
TI  - Biochemical differences between red and white muscle.

PMID- 14957047
TI  - Reported gamma glutamyl activation of peptide-bond synthesis.

PMID- 14957046
TI  - Paper electrophoresis of serum proteins.

PMID- 14957048
TI  - Inhibition of lysine decarboxylase from E. coli by homologous rabbit antibody.

PMID- 14957049
TI  - Purification of a lipid material ('cord factor') obtained from young cultures of
      tubercle bacilli.

PMID- 14957050
TI  - Toxic principle of Lathyrus sativus.

PMID- 14957051
TI  - Toxicity of dextran in rats.

PMID- 14957052
TI  - Viability of Conispiculum guindiensis in Calotes versicolor preserved in
      formalin.

PMID- 14957053
TI  - Effect of nitrite on the nuclear structure in the silkworm.

PMID- 14957054
TI  - Some effects of ultra-violet radiation on Lemna minor.

PMID- 14957055
TI  - Leonardo Da Vinci, artist and man of science (1452-1519).

PMID- 14957056
TI  - Effect of drying upon the absorption spectra of haemoglobin and its derivatives.

PMID- 14957057
TI  - Transaminases for pyridoxamine and purines.

PMID- 14957058
TI  - Formation and breakdown of pentose phosphates by liver fractions.

PMID- 14957059
TI  - Glucuronide decomposition in the digestive tract.

PMID- 14957060
TI  - Triosephosphate dehydrogenase and glucose-6-phosphate dehydrogenase in the pea
      plant.

PMID- 14957061
TI  - GLYCEROL as a nutritive for Vibrio cholerae.

PMID- 14957062
TI  - Lepine and Sautter's disease in Great Britain.

PMID- 14957063
TI  - Infra-red brooding and the crooked-toe problem in chicks.

PMID- 14957064
TI  - [The National Institute of Public Health].

PMID- 14957065
TI  - [Diagnosis of peripheral circulatory disorders].

PMID- 14957066
TI  - [Osteoid osteoma].

PMID- 14957067
TI  - [Isolation of the herpes simplex virus from a patient with acute encephalitis].

PMID- 14957068
TI  - [Commotio cerebri (brain concussion)].

PMID- 14957069
TI  - [Acrodynia caused by mercury poisoning].

PMID- 14957070
TI  - [Qualitative acetone determination in urine].

PMID- 14957071
TI  - [The importance of death certificate B in mortality statistics by causes of
      death].

PMID- 14957072
TI  - [Vaccination against yellow fever].

PMID- 14957073
TI  - In memoriam Dr. K. H. J. Barendrecht.

PMID- 14957074
TI  - [African encephalitis].

PMID- 14957075
TI  - [Hemispherectomy in cerebral hemiatrophy and porencephaly].

PMID- 14957076
TI  - [Certain syndromes in South African natives].

PMID- 14957077
TI  - [Results with ACTH].

PMID- 14957078
TI  - [Pitch and quality, two components in musical tone perception].

PMID- 14957079
TI  - [A new form of irregularly dominant deaf-mutism as a part of a more extensive
      syndrome].

PMID- 14957080
TI  - [Multiple tumors].

PMID- 14957081
TI  - [Total plastic surgery of the nose].

PMID- 14957082
TI  - [Malignant tumors of the epipharynx].

PMID- 14957083
TI  - [Sinusitis in children].

PMID- 14957084
TI  - [The fistula and pseudofistula symptom].

PMID- 14957085
TI  - [Facial plastic surgery].

PMID- 14957086
TI  - [Soundproof construction in the otorhinolaryngological clinic of the university
      of Leiden].

PMID- 14957087
TI  - [Etiology, transmission, serodiagnosis and prevention of typhus].

PMID- 14957088
TI  - [The serological aspect of acquired hemolytic anemia].

PMID- 14957089
TI  - [Chronically positive sputum culture in lung tuberculosis].

PMID- 14957090
TI  - [Treatment in a case of snake bite].

PMID- 14957091
TI  - [A case of disseminated lupus erythematosus with slight skin anomalies].

PMID- 14957092
TI  - [Blood and urinary proteins in bullous dermatoses].

PMID- 14957093
TI  - [Cutaneous melanofibroma].

PMID- 14957094
TI  - [Consciousness and cerebral cortex].

PMID- 14957095
TI  - [Fractures of the malar bone].

PMID- 14957096
TI  - [Prolonged dicumarol therapy of severe angina pectoris and recurrent heart
      infarct].

PMID- 14957097
TI  - [Determination of the maximum excretory capacity of the liver as a highly
      sensitive liver function test].

PMID- 14957098
TI  - [Isonicotinic acid hydrazide].

PMID- 14957099
TI  - [The relation of the month of birth to schizophrenia and manic depression].

PMID- 14957100
TI  - The physiology of adaptive behaviour.

PMID- 14957101
TI  - [The morphological character of the area postrema].

PMID- 14957102
TI  - [Hypertelorism].

PMID- 14957103
TI  - [The kinetic apparatus of the human finger; anatomical structure and functional
      significance].

PMID- 14957104
TI  - [The structure of the substanita spongiosa].

PMID- 14957105
TI  - [An unusual anomaly of the lingual nerve in a human embryo].

PMID- 14957106
TI  - [Systems of fibers in the basal ganglia].

PMID- 14957107
TI  - [Determination of fitness in parts of regenerating extremities of amphibia].

PMID- 14957108
TI  - [Microspirometer for simultaneous determination of oxygen consumption and carbon
      dioxide production].

PMID- 14957109
TI  - [Netherlands' contribution to progress in medical science, 1900-1950; obstetrics
      and gynecology].

PMID- 14957110
TI  - [Clinical and psychological aspects of anxiety hysteria].

PMID- 14957111
TI  - [Post partum inversion of the uterus].

PMID- 14957112
TI  - [Study of salve bases used for sulfanilamides and penicillin].

PMID- 14957113
TI  - [Philosophy of mental patients].

PMID- 14957114
TI  - [Nutrition in Indonesia..].

PMID- 14957115
TI  - [In memoriam Johan Marcus Baart de la Faille].

PMID- 14957116
TI  - [Not Available].

PMID- 14957117
TI  - [Clinical use of electromyography].

PMID- 14957118
TI  - [Eosinophils and mast cells].

PMID- 14957119
TI  - [Preliminary results in ACTH and cortisone therapy of skin diseases].

PMID- 14957120
TI  - [Histological and cytological findings in bullous dermatoses].

PMID- 14957121
TI  - [In memoriam Prof. Dr. Jan van der Hoeve].

PMID- 14957122
TI  - [Pathological conception of one's own body].

PMID- 14957123
TI  - [The effect of subcutaneous injection of certain gases on gas exchange during
      anesthesia].

PMID- 14957124
TI  - [Hypertension in unilateral kidney disease of the Van Houtum-Goldblatt type].

PMID- 14957125
TI  - [Diathermocoagulation in therapy of premenopause hemorrhage and uterine
      carcinoma].

PMID- 14957126
TI  - [Atrophy of small hand muscles due to heart infarct].

PMID- 14957127
TI  - [Results of lung resection for bronchiectasis].

PMID- 14957128
TI  - [Treatment of hypochromic anemia].

PMID- 14957129
TI  - [Benign lymphoreticulosis].

PMID- 14957130
TI  - [A foreign body in the rectal ampulla of an infant].

PMID- 14957131
TI  - [A case of bulbar crossing of the pyramidal tract in man].

PMID- 14957132
TI  - [A case of traumatic chorea].

PMID- 14957133
TI  - [A case of congenital analgesia].

PMID- 14957134
TI  - [Pathological findings in a case of organic psychopathy].

PMID- 14957135
TI  - [Medulloblastoma].

PMID- 14957136
TI  - [Diagnosis of abdominal diseases in the tropics].

PMID- 14957137
TI  - [Hazards of vitamin B1 injections].

PMID- 14957138
TI  - [Hydronephrosis due to congenital abnormality of the renal blood vessels].

PMID- 14957139
TI  - [Erythema Infectiosum].

PMID- 14957140
TI  - [Endogenous protein breakdown in uremia].

PMID- 14957141
TI  - [An epidemic of Bornholm disease].

PMID- 14957142
TI  - [Method of taking roentgenograms and duplicates simultaneously].

PMID- 14957143
TI  - [Prevention of measles in infants].

PMID- 14957144
TI  - [In memoriam W. F. J. Uffelie].

PMID- 14957145
TI  - [In memoriam Dr. M. L. H. S. Menko].

PMID- 14957146
TI  - [Photography of the optic canal].

PMID- 14957147
TI  - [Amblyopic nystagmus in non-amblyopic subjects].

PMID- 14957148
TI  - [Viral eye diseases].

PMID- 14957149
TI  - [Results of early strabismus therapy].

PMID- 14957150
TI  - [Mathematical determination of diffusion of choroid sarcoma infiltration].

PMID- 14957151
TI  - [Determination of orbital tension].

PMID- 14957152
TI  - [Chart for diagnosis of strabismus].

PMID- 14957153
TI  - [Seasonal variation in retinal detachment].

PMID- 14957154
TI  - [Tapetoretinal degeneration].

PMID- 14957155
TI  - [Exchange transfusion in kernicterus].

PMID- 14957156
TI  - [Food poisoning due to S. bovis morfibicans].

PMID- 14957157
TI  - [Brill-Baehr-Rosenthal disease, a reticulosis].

PMID- 14957158
TI  - [Acoustic trauma].

PMID- 14957159
TI  - [Stridor in congenital laryngeal cyst].

PMID- 14957160
TI  - [Anticoagulant therapy of heart infarct].

PMID- 14957161
TI  - [Treatment of hypochromic anemia].

PMID- 14957162
TI  - [Treatment of hypochromic anemia].

PMID- 14957163
TI  - [Serodiagnosis in two cases of cold hemoglobinuria].

PMID- 14957164
TI  - [The Jaksch-Hayem-Luzet syndrome].

PMID- 14957165
TI  - [A case of endemic sprue with macrocytic anemia and Howell-Jolly bodies].

PMID- 14957166
TI  - [Rheumatoid arthritis and pulmonary changes].

PMID- 14957167
TI  - [Psychosomatic medicine and primary chronic polyarthritis].

PMID- 14957168
TI  - [Antibodies in nasal secretion after vaccination with influenza virus and their
      possible immunological significance].

PMID- 14957169
TI  - [Coxsackie virus in pleurodynia and poliomyelitis].

PMID- 14957170
TI  - [The semicentennial of Hellendoorn].

PMID- 14957171
TI  - [Ancylostomiasis].

PMID- 14957172
TI  - [Gunshot fractures with nerve lesions].

PMID- 14957173
TI  - [Hexachlorophene (G11) as skin disinfectant].

PMID- 14957174
TI  - [Hepatitis in young infants].

PMID- 14957175
TI  - [Perniosis in school children, a sign of hypoproteinosis].

PMID- 14957176
TI  - [Calomel poisoning].

PMID- 14957177
TI  - [Blood sugar determination by the anthranone method].

PMID- 14957178
TI  - [Annual report for 1951 of the Nederl. org. voor toegepast-natuurwet. onderzoek
      ten behoeven van de volksgezondh].

PMID- 14957179
TI  - [In memoriam D. Baggelaar].

PMID- 14957180
TI  - [Bronchography].

PMID- 14957181
TI  - [Leisure time activities of the working woman].

PMID- 14957182
TI  - [Reflections on methodology in psychology of woman, with considerations on
      descriptive phenomenology and analytic psychology].

PMID- 14957183
TI  - [A scientific approach to psychodiagnosis].

PMID- 14957184
TI  - [Synthesis in psychodiagnosis; postscript].

PMID- 14957185
TI  - [The feeling of being ridiculous].

PMID- 14957186
TI  - [Groups and group formation].

PMID- 14957187
TI  - [Genetic psychology of the means of interhuman contact].

PMID- 14957188
TI  - [Comments on problems of the practicing psychologist].

PMID- 14957189
TI  - [Psychoanalytical re-education].

PMID- 14957190
TI  - Investigation through teaching.

PMID- 14957191
TI  - Fats in the pathologic placenta.

PMID- 14957192
TI  - [Fetal and placental circulation].

PMID- 14957193
TI  - [Hematoma of the abdominal wall in a woman].

PMID- 14957194
TI  - [Demonstration of a patient after prolapse operation].

PMID- 14957195
TI  - [Commemoration on Prof. Dr. J.L.B. Engelhard].

PMID- 14957196
TI  - [The omentum in plastic surgery of intractable rectovesicovaginal fistulas].

PMID- 14957197
TI  - [Sludge formation and thrombus formation].

PMID- 14957198
TI  - [Leukoplakia].

PMID- 14957199
TI  - [Santiago Ramon Y Cajal, 1852-1934].

PMID- 14957200
TI  - [The field of esthetic perception and its pathological variations; comments on
      the problem of delusion].

PMID- 14957201
TI  - [Frontal lobe and personality].

PMID- 14957202
TI  - [Pathological physiology of the dementia caused by phenylpyruvic acid].

PMID- 14957203
TI  - [Chronic lupus erythematosus with acute exacerbation and manifestation on the
      central nervous system].

PMID- 14957204
TI  - [On telepathy].

PMID- 14957205
TI  - [Automatic performance of encephalography by the means of an apparatus (apparatus
      for encephalography)].

PMID- 14957206
TI  - [Indication and technique for nitrous oxide encephalo].

PMID- 14957207
TI  - [The 24 hour encephalogram; additional results].

PMID- 14957208
TI  - [Comment on proposal to a federal law on the court order to deprive and limit
      personal freedom].

PMID- 14957209
TI  - [Meeting of the Rhine-Westphalian Neurologists' Association in Essen].

PMID- 14957210
TI  - The essential mechanism in myotonia; an electromyographic study.

PMID- 14957211
TI  - Cerebral angiography in diagnosis of subdural hematoma.

PMID- 14957212
TI  - Hypnosis in differentiation of epileptic from convulsive-like seizures.

PMID- 14957213
TI  - Mesantoin in the control of epilepsy.

PMID- 14957214
TI  - Role of food allergy in multiple sclerosis.

PMID- 14957215
TI  - Korsakoff's psychosis associated with cerebral tumors.

PMID- 14957216
TI  - What has neurology to offer child guidance?

PMID- 14957217
TI  - Rehabilitation of the neurologically disabled child.

PMID- 14957218
TI  - Clinical pathological conference: grand mal and petit mal seizures with epileptic
      equivalents.

PMID- 14957219
TI  - Lasegue sign.

PMID- 14957220
TI  - George Boris Hassin, M.D., 1873-1951.

PMID- 14957221
TI  - Diabetes and pregnancy.

PMID- 14957222
TI  - Association of spontaneous mediastinal emphysema and acute myocardial infarction;
      report of two cases.

PMID- 14957223
TI  - Effect of aureomycin on the development of cold agglutinins in primary atypical
      pneumonia.

PMID- 14957224
TI  - Antimicrobial treatment for viral and related infections. I. Antibiotic treatment
      of primary atypical pneumonia.

PMID- 14957225
TI  - WEEKLY clinicopathological exercise: dissecting aneurysm of thoracic and
      abdominal aorta; infarction of spinal cord.

PMID- 14957227
TI  - PLASMA substitutes and defense.

PMID- 14957226
TI  - WEEKLY clinicopathological exercise: perforated gastric ulcer; coronary artery
      disease, with early myocardial infarction.

PMID- 14957228
TI  - Treatment of endometriosis and other gynecologic conditions with large doses of
      estrogens.

PMID- 14957229
TI  - Acrodynia following ingestion of mercurial ointment; late dental sequelae.

PMID- 14957230
TI  - Therapeutic application of heat: its uses and abuses.

PMID- 14957231
TI  - Acute appendicitis during menstruation.

PMID- 14957232
TI  - Diabetes mellitus.

PMID- 14957233
TI  - Two unusual cases of ectopic gestation.

PMID- 14957234
TI  - Cervical cytology as a practical screening procedure for cancer.

PMID- 14957235
TI  - WEEKLY clinicopathological exercise: metastatic carcinoma of pleura, from
      carcinoma of breast.

PMID- 14957236
TI  - WEEKLY clinicopathological exercise: thrombosis of abdominal aorta, with
      occlusion of renal and iliac arteries; renal infarction, left.

PMID- 14957237
TI  - POSTGRADUATE Medical Institute.

PMID- 14957239
TI  - COMMUNICABLE diseases in Massachusetts for July, 1952.

PMID- 14957238
TI  - MASSACHUSETTS Department of Public Health; laboratories approved for diagnostic
      serologic tests for syphilis.

PMID- 14957240
TI  - Importance of the blood groups in laboratory and clinical medicine.

PMID- 14957241
TI  - The clinical use of norepinephrine in the treatment of shock accompanying
      myocardial infarction and other conditions.

PMID- 14957242
TI  - Pulmonary function in convalescent poliomyelitic patients. III. Compliance of the
      lungs and thorax.

PMID- 14957243
TI  - Adiposis dolorsa (Dercum's disease).

PMID- 14957244
TI  - Diabetes mellitus.

PMID- 14957245
TI  - Revolution in fiction.

PMID- 14957246
TI  - WEEKLY clinicopathological exercise: rheumatic heart disease, with mitral
      stenosis; ball-valve thrombus, left auricle.

PMID- 14957247
TI  - WEEKLY clinicopathological exercise: eosinophilic granuloma of rib.

PMID- 14957248
TI  - UNFINISHED business.

PMID- 14957249
TI  - NATIONAL Medical Library.

PMID- 14957250
TI  - SHERLOCK Holmes vs. Mike Hammer.

PMID- 14957251
TI  - Resettlement of refugee physicians in the United States.

PMID- 14957252
TI  - Recent experiences with acute perforation of peptic ulcers at the Massachusetts
      General Hospital; a review of 288 cases.

PMID- 14957253
TI  - Rubella (German measles) observations on an epidemic, with particular reference
      to lymphadenopathy.

PMID- 14957254
TI  - Boston Medical Library report of the librarian.

PMID- 14957255
TI  - Background to Britain's health service.

PMID- 14957256
TI  - Causes of cutting-oil dermatitis.

PMID- 14957257
TI  - WEEKLY clinicopathological exercise: arterial embolization and infarction, right
      kidney; lower-nephron nephrosis (ischemic nephrosis).

PMID- 14957258
TI  - WEEKLY clinicopathological exercise: glioblastoma multiforme, left cerebral
      hemisphere, midbrain and pons, with hemorrhage.

PMID- 14957260
TI  - [Determination of the air purifying efficiency of Electrolux vacum cleaners].

PMID- 14957259
TI  - WILLIAM F, Lynch, M.D. (1879-1942).

PMID- 14957261
TI  - [Public health authorities and housing construction].

PMID- 14957262
TI  - [The restoration of Ronne and Nexo on Bornholm].

PMID- 14957263
TI  - [Food poisoning caused by Clostridium perfringens (welchii); preliminary report].

PMID- 14957264
TI  - Inductive effect in odontogenic tumor.

PMID- 14957265
TI  - [Conservative and surgical therapy of condylar fractures].

PMID- 14957266
TI  - [The meeting of the American Dental Society, August 1-4, 1951].

PMID- 14957267
TI  - [Orthodontic treatment with removable plates in school dentistry].

PMID- 14957268
TI  - [The treatment of deciduous teeth in daily practice].

PMID- 14957269
TI  - PUBLIC dental care in Norway.

PMID- 14957270
TI  - [Gingivectomy and postoperative treatment].

PMID- 14957271
TI  - [Annual report of the department of dentistry and oral surgery, Ulleval sykehus,
      for 1951].

PMID- 14957272
TI  - Abuse of data on the biologic value of proteins.

PMID- 14957273
TI  - METABOLISM of water and electrolytes in patients with liver disease.

PMID- 14957274
TI  - HEXOSE phosphate oxidation and pentose formation.

PMID- 14957275
TI  - DESTRUCTION of thiamine in purified diets.

PMID- 14957276
TI  - AMINO acid imbalance.

PMID- 14957278
TI  - OBESITY.

PMID- 14957277
TI  - GALACTOSE utilization and conversion to glycogen.

PMID- 14957279
TI  - VITAMIN K emulsions in anticoagulant therapy.

PMID- 14957280
TI  - NUTRITION and susceptibility to tuberculosis.

PMID- 14957281
TI  - RIBOFLAVIN requirements in pregnancy.

PMID- 14957282
TI  - MONKEY antianemia factor.

PMID- 14957283
TI  - VITAMIN B12 and growth of premature infants.

PMID- 14957284
TI  - DIET and insulin effect on diabetes and cataract development in rats.

PMID- 14957285
TI  - ARTERIOSCLEROSIS in the golden hamster.

PMID- 14957286
TI  - VITAMIN E activity of methylene blue.

PMID- 14957287
TI  - INTERCONVERSION among nonessential amino acids.

PMID- 14957288
TI  - FAT in nutrition.

PMID- 14957289
TI  - PREVENTION of hemorrhage by rutin.

PMID- 14957290
TI  - FOOD intake and nocturnal diuresis in sprue.

PMID- 14957291
TI  - Fat metabolism in the early 1900's.

PMID- 14957292
TI  - EFFECT of surgery on plasma levels of essential amino acids.

PMID- 14957293
TI  - INTESTINAL flora of infants.

PMID- 14957294
TI  - RESTRICTION of food intake and health.

PMID- 14957295
TI  - NUTRIENT absorption following intestinal resection.

PMID- 14957296
TI  - GASTROINTESTINAL x-ray studies in thiamine deficiency.

PMID- 14957297
TI  - FEEDING problems during flight.

PMID- 14957298
TI  - SOURCE of lysine, tyrosine and phosphorus for casein synthesis.

PMID- 14957299
TI  - NIACIN and tryptophan in feline nutrition.

PMID- 14957300
TI  - ACTION of thyroid, choline and inositol on tissue cholesterol and lipids.

PMID- 14957301
TI  - INFLUENCE of route of administration and of sex on serum iron levels.

PMID- 14957302
TI  - AUREOMYCIN, dietary proteins and the growth of mice.

PMID- 14957303
TI  - ENZYMATIC conversion of phenylalanine to tyrosine.

PMID- 14957304
TI  - INSULIN and cocarboxylase in diabetes.

PMID- 14957305
TI  - RELATION between folacin and tissue ascorbic acid.

PMID- 14957306
TI  - PHOTOSYNTHESIS and coenzymes.

PMID- 14957307
TI  - UTILIZATION of vitamin B12.

PMID- 14957308
TI  - PANTOTHENIC acid deficiency and adrenal insufficiency.

PMID- 14957310
TI  - LIPOTROPIC supplements in fatty cirrhosis.

PMID- 14957309
TI  - False estimates of adult requirements.

PMID- 14957311
TI  - KWASHIORKOR in Africa.

PMID- 14957312
TI  - ALKAPTONURIA.

PMID- 14957313
TI  - MINERAL oil dosage and vitamin A absorption.

PMID- 14957314
TI  - ASSESSMENT of growth and development in children.

PMID- 14957315
TI  - IODINE-tagged albumin in cirrhotic patients.

PMID- 14957316
TI  - INFLUENCE of tocopherol intake on vitamin A content of milk.

PMID- 14957317
TI  - MODE of action of antibiotics in poultry nutrition.

PMID- 14957318
TI  - PYRIDOXINE and synthesis of pyridine nucleotides.

PMID- 14957319
TI  - NERVOUS system and animal behavior in B-complex deficiencies: conditioned
      responses.

PMID- 14957320
TI  - STRAIN variation and caries susceptibility.

PMID- 14957321
TI  - METABOLIC fate of orally administered choline.

PMID- 14957322
TI  - BLOOD glucose and the urge to eat.

PMID- 14957323
TI  - SPECIFICITY of the strepogenin effect on bacterial growth.

PMID- 14957324
TI  - CITROVORUM factor conjugate.

PMID- 14957325
TI  - NIACIN metabolism in pregnancy.

PMID- 14957326
TI  - LABILE methyl synthesis.

PMID- 14957327
TI  - [Resection of the superior hypogastric plexus in pelvic pain].

PMID- 14957329
TI  - [Considerations on the induction of labor].

PMID- 14957328
TI  - [Hyper rotation and deflexion of the fetal head in pelvic presentation].

PMID- 14957330
TI  - [Evaluation of the effect of estrogen preparations. III. Comparative action of
      one milligram of estradiol benzoate and sublingual administration of estrogens].

PMID- 14957331
TI  - [Diabetes and pregnancy; considerations on a clinical case].

PMID- 14957332
TI  - [Paraplegia and labor].

PMID- 14957333
TI  - [Surgical treatment of anovulatory cycles].

PMID- 14957334
TI  - [Hysterosalpingography and new apparatus].

PMID- 14957335
TI  - [Absence of the vas deferens; considerations on four cases].

PMID- 14957336
TI  - [Maternofetal blood incompatibility as an indication for the interruption of
      pregnancy].

PMID- 14957337
TI  - [Surgical treatment of senile genital prolapse with modified Labhardt operation].

PMID- 14957338
TI  - [Carcinoma of Bartholin's gland].

PMID- 14957339
TI  - Research in fungicides results in protection for fruit packers and sorters
      against dermatitis.

PMID- 14957340
TI  - PHS time study uncovers ways to extend nurses' services.

PMID- 14957341
TI  - Shaking machine back for separatory funnels.

PMID- 14957342
TI  - Industrial toxicology; monofluoroacetic acid.

PMID- 14957343
TI  - Dollars and cents value of industrial hygiene in industry.

PMID- 14957345
TI  - PLANT tours for physicians and nurses recommended in Wisconsin.

PMID- 14957344
TI  - SOLVENT vapors burned in stacks saves company money.

PMID- 14957346
TI  - Contamination of drinking water results from cross-connections with machining
      operations.

PMID- 14957347
TI  - Noisy industries should install hearing conservation programs.

PMID- 14957348
TI  - FIRESTONE employees participate in health and safety programs.

PMID- 14957349
TI  - MOUNTAINS, desert, and jungle in Peru make progress in industrial health slow.

PMID- 14957350
TI  - Industrial nurses should practice preventive care.

PMID- 14957351
TI  - Leaded gasoline used in carbon blasting poisons mechanic.

PMID- 14957352
TI  - Experimental inhalation of lead by human subjects.

PMID- 14957353
TI  - Health councils plan and act for community improvement.

PMID- 14957354
TI  - Economics problems of older population necessitate re-evaluation of workers'
      usefulness.

PMID- 14957355
TI  - Philadelphia Visiting Nurse Society serves industries successfully.

PMID- 14957356
TI  - Harmful effects of light on the eyes. Part I.

PMID- 14957357
TI  - [A case of late reimplantation].

PMID- 14957358
TI  - [Conservative one-stage therapy of deciduous gangrenous and fistulous incisors].

PMID- 14957359
TI  - [XXVes days Dental Paris, 21-25 November 1951].

PMID- 14957360
TI  - [Anesthesia with trylene].

PMID- 14957361
TI  - [A case of germination of teeth].

PMID- 14957362
TI  - [Analgesia with trichlorethylene].

PMID- 14957363
TI  - [Crown reconstruction; metallic caps with acrylic vestibular incrustation].

PMID- 14957365
TI  - Experimental dental caries in animals; a historical review.

PMID- 14957364
TI  - The presence or absence of bacteria in gingival pockets and the reaction in
      healthy pockets to certain pure cultures; a bacteriological and histological
      investigation.

PMID- 14957366
TI  - Experimental dental caries in golden hamsters with special reference to the
      examination and recording technique.

PMID- 14957367
TI  - [Social dentistry in Italy].

PMID- 14957368
TI  - [The role of school dental service in dentistry].

PMID- 14957369
TI  - [Clinical and biological manifestations in dental focal infection].

PMID- 14957370
TI  - [Diagnosis and therapy of the giant cell granuloma of the jaws].

PMID- 14957371
TI  - [Ligature of the arteria carotis communis and carotis interna].

PMID- 14957372
TI  - [The crown technique; literature review from 1945-1950].

PMID- 14957373
TI  - [Pathogenesis of primary glaucoma].

PMID- 14957374
TI  - [Ophthalmology in the canton Glarus].

PMID- 14957375
TI  - [The effect of iridectomy in chronic congestive glaucoma].

PMID- 14957376
TI  - [Sympathetic ophthalmia after iridencleisis with extensive cell accumulation over
      the retinal vessels].

PMID- 14957377
TI  - [Secondary glaucoma with iridic vascular neoformation].

PMID- 14957378
TI  - [Clinical studies on vascular neoformation in the iris].

PMID- 14957379
TI  - [Acute concomitant strabismus].

PMID- 14957380
TI  - [Therapy of eye muscle injuries].

PMID- 14957381
TI  - [Prevention of hemorrhage in operations on the eyeball].

PMID- 14957382
TI  - [Perforating wounds, infectious foci, sympathetic ophthalmia].

PMID- 14957383
TI  - [Iridic cysts].

PMID- 14957384
TI  - [Clinical value of radiography of the optic canal].

PMID- 14957385
TI  - [Quantitative assessment of functional visual disorders, with reference to a case
      of optic nerve injury].

PMID- 14957386
TI  - [Retrobulbar neuritis after acute chlorohydrocarbon poisoning].

PMID- 14957387
TI  - [Unilateral papilledema, pseudoneuritis and pseudopapilledema].

PMID- 14957388
TI  - [A spot suggesting retinal perforation].

PMID- 14957389
TI  - [Critical studies on failure of retinal operations].

PMID- 14957390
TI  - [A new slit lamp fluorometer].

PMID- 14957391
TI  - [Electrophoresis of the aqueous humor].

PMID- 14957392
TI  - [Unilateral aphakia and contact lenses].

PMID- 14957393
TI  - [Specific indications for contact lenses in neuroparalytic keratitis and
      albinism].

PMID- 14957394
TI  - [Indications and counterindications in orthoptic treatment of concomitant
      convergent strabismus].

PMID- 14957395
TI  - [The importance of method of administration in antibiotic therapy].

PMID- 14957396
TI  - [Cortisone; indication and use].

PMID- 14957397
TI  - [Hazards of cortisone therapy].

PMID- 14957398
TI  - [Homeopathy in ophthalmology].

PMID- 14957399
TI  - [Color photography in clinical instruction].

PMID- 14957400
TI  - [Congenital Graefe's pseudosign].

PMID- 14957401
TI  - [Acute keratoconus in a child].

PMID- 14957402
TI  - [Results with the Middlebrook-Dubos serotest in tuberculosis].

PMID- 14957403
TI  - [Clinical results with new isotonic and pH stable collyria].

PMID- 14957404
TI  - [Ocular symptoms in gargoylism].

PMID- 14957405
TI  - [Faulty retinal correspondence].

PMID- 14957406
TI  - [Coordimetric diagnosis with Goldmann's perimeter].

PMID- 14957407
TI  - [Chronic uveitis in bronchiectasis].

PMID- 14957408
TI  - [A specific form of recidivating choroiditis].

PMID- 14957409
TI  - [A new adaptometer].

PMID- 14957410
TI  - [Treatment of epithelial lesions of the cornea].

PMID- 14957411
TI  - [Determination of the tension in the aqueous humor with the electronic tonometer.
      III. Results in glaucomatous subjects treated with retrociliary diathermy].

PMID- 14957412
TI  - Cholinesterase activity in the serum and aqueous in glaucoma.

PMID- 14957413
TI  - The late bodies of trachoma.

PMID- 14957414
TI  - [The effect of x-rays as a cause of fetal misdevelopment].

PMID- 14957415
TI  - Lens replacement of accommodative activity.

PMID- 14957416
TI  - [Analysis of the human electroretinogram].

PMID- 14957417
TI  - [Tertiary syphilis of the larynx].

PMID- 14957418
TI  - [Tonsillar test; variation of the number of leukocytes following administration
      of the galvanic current and its indicative value].

PMID- 14957419
TI  - [Endocranial symptoms in thrombophlebitis of the lateral sinus].

PMID- 14957420
TI  - [Experimental agranulocytosis].

PMID- 14957421
TI  - [Audiometric curve in chronic otomastoiditis and its variations following
      surgical intervention].

PMID- 14957422
TI  - [Leukocytosis following tonsillectomy].

PMID- 14957423
TI  - [Tonsillar hemogram; control of the treatment with nitrogen mustards of
      reticuloendotheliosis].

PMID- 14957424
TI  - [Allergy and otitis in infant].

PMID- 14957425
TI  - [Considerations of the surgical treatment of so-called idiopathic megaesophagus].

PMID- 14957426
TI  - [Apophysis of the crista galli in pathogenesis of fronto-basilar chronic
      hyperergic phlegosis].

PMID- 14957427
TI  - [Monopolar, uniauricular and biauricular galvanic vestibular examination in
      normal subjects].

PMID- 14957428
TI  - [Intentional speech disorders].

PMID- 14957429
TI  - [Problem of laryngeal stenosis in diphtheric and nondiptheric laryngitis;
      incidence, clinical aspects and therapeutic considerations].

PMID- 14957430
TI  - [Lipomatous pseudo-hypertrophy of the parotid].

PMID- 14957431
TI  - [Cases of paralysis of the last four cranial nerves of traumatic origin].

PMID- 14957432
TI  - [Functional activation of the reticulo-histiocytary apparatus of the middle ear
      and possibility of its relation with the pathogenesis of otitis].

PMID- 14957433
TI  - [Otosclerosis and endocrine disorders].

PMID- 14957434
TI  - [Case of nasopharyngeal tuberculosis].

PMID- 14957435
TI  - [Selection of antibiotics in otorhinolaryngology].

PMID- 14957436
TI  - [Streptomycin in the treatment of tuberculous infections of the primary air
      passages].

PMID- 14957437
TI  - [Variations of chromatophores of the pia mater following injection of pyrogenic
      substances].

PMID- 14957438
TI  - [Postoperative dysphagia in tonsillectomy in adult].

PMID- 14957439
TI  - [Consideration on anesthesia].

PMID- 14957440
TI  - [Tullio's reflexes following fenestration].

PMID- 14957441
TI  - [Antihemorrhagic properties of associated vitamins C, P, K and their use in
      otorhinolaryngology].

PMID- 14957442
TI  - [Cystic fibrous osteodystrophy of the ethmoid].

PMID- 14957443
TI  - [Laryngeal asphyxia due to cancer and tracheotomy; certain reflexions].

PMID- 14957444
TI  - [New indications for beta radiations therapy with application of Crowe's radium
      catheter in the field of otorhinolaryngology].

PMID- 14957445
TI  - [Case of eosinophil granuloma of the frontal body with meningeal invasion].

PMID- 14957446
TI  - [Febricula in otorhinolaryngology].

PMID- 14957447
TI  - [Phonetic aspects of paralysis of the inferior laryngeal nerve].

PMID- 14957448
TI  - [Certain secretory olfactory secretory reflexes considered as the expression of
      olfactory capacity in laryngectomized].

PMID- 14957449
TI  - [Clinical aspects of permeability of the eustachian tube during respiration].

PMID- 14957450
TI  - [Otorhinolaryngological manifestations in Sjoegren syndrome].

PMID- 14957451
TI  - [Audiometric differential diagnosis auditory deficiency lesions of perceptive
      nature].

PMID- 14957452
TI  - [Anesthetic infiltration of the pre-epiglottic space in the treatment of certain
      forms of asthma, spasmodic cough, and pharyngo-esophageal spastic syndrome].

PMID- 14957453
TI  - [Unusual case of acute loss of acute (surgical) domiciliary right of the
      herniated and prolapsed intestine observed in 55-day-old infant].

PMID- 14957454
TI  - [Functional surgery of chronic suppurative otitis media].

PMID- 14957455
TI  - [Neurolabyrinthopathy in retinitis pigmentosa].

PMID- 14957456
TI  - [So-called granulosa cell tumors of the tongue].

PMID- 14957457
TI  - [Carotid-cavernous aneurysm due to cranial fracture].

PMID- 14957458
TI  - [Value of audiometry in ocular diseases].

PMID- 14957459
TI  - [Study on psycho-facial reflexes].

PMID- 14957460
TI  - [Study on the embryonal development of the human pharynx].

PMID- 14957461
TI  - [Paranasal sinus in children with tracheal tube].

PMID- 14957462
TI  - [Observations on surgery of ozena].

PMID- 14957463
TI  - [Neurovegetative focal infection].

PMID- 14957464
TI  - [Epithelium of the tonsillar crypt in lympho-leukocytary infiltration;
      histopathological and general considerations].

PMID- 14957465
TI  - [Two cases of cerebellar hernia consecutive to acute mastoiditis and
      thrombophlebitis of the lateral sinus].

PMID- 14957466
TI  - [Surgical treatment of atresia auris congenita].

PMID- 14957467
TI  - [Considerations on a case of neurofibrosarcomatosis; anatomical and clinical
      considerations].

PMID- 14957468
TI  - [Carcinoma of the Morgagni's ventricle].

PMID- 14957469
TI  - [Tonsillar tuberculosis and tonsillectomy].

PMID- 14957470
TI  - [Pathogenic interpretation of so-called cochlear block].

PMID- 14957471
TI  - [Considerations on vestibular reflex asymmetry].

PMID- 14957472
TI  - [Effect of insulin on the endolabyrinthine pressure].

PMID- 14957473
TI  - [Surgical treatment of cholesteatomatous otorrhea by antrotomy with bone taken
      from the mastoid cortex].

PMID- 14957474
TI  - [Observations on the effect of antihistamines on compensating labyrinthic
      syndrome].

PMID- 14957475
TI  - [Association of laryngeal cancer, pulmonary syphilis, and lymph node tuberculosis
      in the same patient].

PMID- 14957476
TI  - [Topic action of phosphotungstic acid].

PMID- 14957477
TI  - [Metastases of laryngeal carcinoma].

PMID- 14957478
TI  - [Pharyngeal and tonsillar fibromatosis].

PMID- 14957479
TI  - [Etiopathogenic considerations on a case of diffuse phlegmonous esophagitis].

PMID- 14957480
TI  - [Consideration on the rhythm of vestibular reflex].

PMID- 14957481
TI  - [Maxillo-facial eosinophilic granuloma; morphological and clinical
      considerations].

PMID- 14957482
TI  - [Peroral endoscopy in bronchial tumors].

PMID- 14957483
TI  - [Structural variations and interpretation of tonsillar reticulo-endotheliosis].

PMID- 14957484
TI  - [Pietro Caliceti].

PMID- 14957485
TI  - [Clinico-audiometric observations in rheumatism].

PMID- 14957486
TI  - [Radiological study of laryngeal carcinoma].

PMID- 14957487
TI  - [Procedure of electrolytic decalcification in histological study of the temporal
      bone].

PMID- 14957488
TI  - [Use of pentamethonium and hexamethonium in facial plastic surgery].

PMID- 14957489
TI  - [Report of the first European conference of the International Association for the
      study of Bronchi, 21-22 April, 1951].

PMID- 14957490
TI  - [Proposal for an international forum on paradental nomenclature and
      classification].

PMID- 14957491
TI  - [Comparative studies on the treatment of periodontal disease].

PMID- 14957492
TI  - [Partial syndesmotomy; contribution on the treatment of certain forms of
      periodontal disease, with particular reference to manifestations of vertical
      atrophy].

PMID- 14957493
TI  - [Dental caries and paradontolysis].

PMID- 14957494
TI  - [Bibliography of periodontal disease].

PMID- 14957495
TI  - [13th Congress ARPA International].

PMID- 14957496
TI  - [Pathologic leucocyte granulation in paradontopathies].

PMID- 14957497
TI  - [Statistical studies on paradontopathies among Berbers].

PMID- 14957498
TI  - Pathogeny of parodontolysis.

PMID- 14957499
TI  - [Testosterone propionate in therapy of premenstrual paradontopathies].

PMID- 14957500
TI  - [To H. Siegmund on his 60th birthday].

PMID- 14957501
TI  - [Combined vitamin K with tetanus toxin in the treatment of poliomyelitis].

PMID- 14957502
TI  - [Pathogenesis of anemia in typhoid infection; sideremia and hemoglobin
      metabolism].

PMID- 14957503
TI  - [Incidence of congenital heart disease in Mongoloid subjects].

PMID- 14957504
TI  - [Effect of cobalt salts on hemopoiesis].

PMID- 14957505
TI  - [Effect of cocarboxylases on normal glycemia and on glycemic curve in glucose
      deficiency in children].

PMID- 14957507
TI  - [Treatment of tinea favosa in Calabria].

PMID- 14957506
TI  - [Coproculture in infants and normal and pathologic conditions].

PMID- 14957508
TI  - [Reiter's disease].

PMID- 14957509
TI  - [Vitamin B12 as a growth factor].

PMID- 14957510
TI  - [Hemoptysis in the new born; 9 cases].

PMID- 14957512
TI  - [5th Brazilian convention on puericulture and pediatrics].

PMID- 14957511
TI  - [Acute retention of the urine due to obstruction of the urethra by sulfadiazine
      crystals].

PMID- 14957513
TI  - [2nd Medical convention on maternal and infant hygiene].

PMID- 14957514
TI  - [State protection of child in peoples democracies].

PMID- 14957515
TI  - [Application of antibiotics in combined therapy of dysentery in children].

PMID- 14957516
TI  - [Pathogenesis of bacillary dysentery].

PMID- 14957517
TI  - [Acute chronic dysentery].

PMID- 14957518
TI  - [Clinico-morphological diagnosis of dysentery in children].

PMID- 14957519
TI  - [Nature of dysentery during first three months of life in infants].

PMID- 14957520
TI  - [Dysentery in newborn].

PMID- 14957521
TI  - [Phagocytic activities of leukocytes in various forms of dysentery and its
      diagnostic significance].

PMID- 14957522
TI  - [Changes of the gastric mucosa in infantile dysentery].

PMID- 14957523
TI  - [Levomycetin therapy of dysentery in children].

PMID- 14957524
TI  - [Laboratory indexes in the treatment of dysentery in children with
      synthomycetin].

PMID- 14957525
TI  - [Coprocytological study in dysentery in children].

PMID- 14957526
TI  - [Multiplication of dysenteriae bacilli in preparation of curdled milk products].

PMID- 14957527
TI  - [Effect of methylene blue on dynamic intestinal obstruction in children].

PMID- 14957528
TI  - [One more symptom of chorea].

PMID- 14957529
TI  - [Method of directing activities of the students' scientific clubs in clinical
      departments of the pediatric schools].

PMID- 14957530
TI  - [Present state of the problem of poliomyelitis].

PMID- 14957531
TI  - [Growth factor in cortical dynamics in children].

PMID- 14957533
TI  - [Relation of tonsillitis to rheumatism in children].

PMID- 14957532
TI  - [Roentgenotherapy of poliomyelitis in children].

PMID- 14957535
TI  - [Rheumatic coronary disease in children].

PMID- 14957534
TI  - [Prognostic significance of rheumatic nodules in children].

PMID- 14957536
TI  - [Clinical evaluation of cerebrospinal fluid examination in tuberculous meningitis
      treated with streptomycin].

PMID- 14957537
TI  - [Brief survey of the history of sanatoria for children in USSR].

PMID- 14957538
TI  - [Basic principles in the organization of prevention and control of rheumatic
      diseases in children].

PMID- 14957539
TI  - [Results of activities of rheumatism-prevention centers following unification of
      pediatric hospitals].

PMID- 14957540
TI  - [Results of dispensary observation of the course of rheumatism in adolescents].

PMID- 14957541
TI  - [Treatment of infected burns in children].

PMID- 14957542
TI  - [Adrenocortical tumors in children].

PMID- 14957543
TI  - [Problem of cardiovascular function tests in adolescents].

PMID- 14957544
TI  - [Prophylactic measure in interparoxysmal stages of rheumatism].

PMID- 14957545
TI  - [Effect of the treatment of rheumatic heart disease in children in Kislovodsk on
      the hydrophil tissue test in interparoxysmal stages].

PMID- 14957546
TI  - [Opsonophagocytic index in children in interparoxysmal stage of rheumatism].

PMID- 14957547
TI  - [Effect of the treatment of rheumatism in children in Kislovodsk on
      capillaroscopic changes in interparoxysmal stage].

PMID- 14957548
TI  - [Various forms of stomatitis in children and their therapy].

PMID- 14957549
TI  - [Stomatitis in children and its therapy].

PMID- 14957550
TI  - [Data on trauma in children in Makhachkala in 1946-48].

PMID- 14957551
TI  - [Caloric reaction as the index of reactivity in children].

PMID- 14957552
TI  - [Treatment of chronic dysentery in children with syntomycetin].

PMID- 14957553
TI  - [Dynamics of isolated spontaneously beating frog heart].

PMID- 14957555
TI  - [The role of the sarcosomata in the myocardium].

PMID- 14957554
TI  - [Adequate stimulation for the Bainbridge reflex].

PMID- 14957556
TI  - Direct auscultation and recording of fetal heart sounds.

PMID- 14957557
TI  - [Kinetics of cholinesterase; improvement of Warburg's apparatus].

PMID- 14957558
TI  - [Neuroendocrine physiology of insects].

PMID- 14957559
TI  - [Mechanism of fat resorption in frog].

PMID- 14957560
TI  - [Action potentials of the carotid body dependent of temperature].

PMID- 14957561
TI  - [Periods of activity of mice in lasting darkness].

PMID- 14957562
TI  - [Changes of frequency of periods of activity of mice in constant light and
      lasting darkness].

PMID- 14957563
TI  - [Habit formation, dependent of temperature and endogenous formation of excitation
      of the central nervous system].

PMID- 14957564
TI  - [Measuring of the speed of skin waves in vibrating irritations on man].

PMID- 14957565
TI  - [Two manometers with photoelectric transmission for intravasal measuring of blood
      pressure].

PMID- 14957566
TI  - [Effects of adrenalin and arternol on the spleen].

PMID- 14957567
TI  - [The absolute size of electrocardiographic potentials].

PMID- 14957568
TI  - [Alkaloids of Lobelia symphilitica L..].

PMID- 14957569
TI  - [Water content of dried plasma; its determination].

PMID- 14957570
TI  - [Attempts to diminish the hygroscopity of extractum belladonna].

PMID- 14957571
TI  - [Pancreatic cystadenoma in its clinical, anatomo-pathological and surgical
      entity].

PMID- 14957572
TI  - [Amount of pyruvic acid in blood of surgical subjects with pentothal-curare-ether
      narcosis and the action of co-carboxylase].

PMID- 14957573
TI  - [A case of encapsulating peritonitis].

PMID- 14957574
TI  - [Comparative study of iodide of decamethonium and D-tubocurarine chloride].

PMID- 14957575
TI  - [Histological study of testis after thiouracil therapy].

PMID- 14957576
TI  - [The effect of methyl-bis (beta-chloroethyl) amine (nitrogen mustard) on the
      granulopectic action of the reticuloendothelial system].

PMID- 14957577
TI  - [Effect of hypoxia on the proliferative action of the erythroblast; comparative
      research on the normoblast and megaloblast].

PMID- 14957578
TI  - [Spectrophotometric analyses of the desoxyribonucleic acid content of the nuclei
      in inter-synthesis of the megaloblasts in progressive pernicious anemia].

PMID- 14957579
TI  - [Thiosemicarbazone and basal metabolism in pulmonary tuberculosis].

PMID- 14957580
TI  - [The tubular mass of para-aminohippuric acid; its determination in normal
      conditions and relation to other indices in the evaluation of renal function].

PMID- 14957581
TI  - [Miliary-like pulmonary stasis].

PMID- 14957582
TI  - [Liver diseases following transfusions of blood and blood derivatives].

PMID- 14957583
TI  - [Six cases of infectious mononucleosis].

PMID- 14957584
TI  - [Lipo-fibro-calcareous myopathia].

PMID- 14957585
TI  - [Use of radiographic examination in the study of lipofibro-calcareous myopathia].

PMID- 14957586
TI  - [A clinico-histological case of primary symmetrical lipo-fibro-calcareous
      syndrome of the lower limbs].

PMID- 14957587
TI  - [Art transforms pain into pleasure].

PMID- 14957588
TI  - [Controlled hypotension in reduction of intraoperative hemorrhage].

PMID- 14957589
TI  - [Combination of vaccine therapy and a specific protein therapy with
      administration of antibiotics in the treatment of surgical sepsis].

PMID- 14957590
TI  - [Control of carriers of Mediterranean blood disorder in the province of Reggio
      Emilia].

PMID- 14957591
TI  - [Democedes: first parish physician].

PMID- 14957592
TI  - [A new theory of cardiac decompensation].

PMID- 14957593
TI  - [II Congress of the Italian Society of Gerontology and Geriatrics].

PMID- 14957594
TI  - [I National Congress of Medical Gymnastics].

PMID- 14957595
TI  - [Origins of experimental biology and Father Spallanzi].

PMID- 14957596
TI  - [Variations of serum lipids during administration of TB 1/698; comparison of TB
      1/698 and cortisone].

PMID- 14957597
TI  - [Cortisone in alkapionuric osteoarthrosis].

PMID- 14957598
TI  - [Effects of choline in hyperfunctioning thyroid adenoma in a child].

PMID- 14957599
TI  - [Thoraco-abdominal wound].

PMID- 14957600
TI  - [Uremic hysteresis; paradoxical phenomenon].

PMID- 14957601
TI  - [Velez's index in pulmonary tuberculosis].

PMID- 14957602
TI  - [Hypochromic anemia in subject with diaphragmatic gastric hernia].

PMID- 14957603
TI  - [Two cases of liver cirrhosis treated with transfusion of ascitic fluid].

PMID- 14957604
TI  - [Meeting of the Italian Society of Plastic Surgery].

PMID- 14957605
TI  - [Moore technique in therapy of transcervical fractures of the femur].

PMID- 14957606
TI  - [Comparative value of examination of duodenal contents and cholecystography in
      preoperative and operative diagnosis of cholelithiasis].

PMID- 14957607
TI  - [Prognosis in tuberculous encephalomeningitis in children].

PMID- 14957608
TI  - [Peculiarity of the clinical picture of malaria in children].

PMID- 14957609
TI  - [Bronchial calculi].

PMID- 14957610
TI  - [The Soto-Hall sign in the fracture of thoracolumbar spine].

PMID- 14957611
TI  - [Antibacterial properties of isonicotinic acid hydrazide].

PMID- 14957612
TI  - [Symptomatic treatment of pulmonary emphysema by pneumoperitoneum].

PMID- 14957613
TI  - [Food poisoning].

PMID- 14957614
TI  - [Report of the II postwar Congress of Anatomists and Anatomopathologists and the
      IX Congress of the Polish Anatomical Society].

PMID- 14957615
TI  - [Forty-years of medical scientific and didactic work of prof. dr. Msciwoj Semerau
      Siemianowski].

PMID- 14957616
TI  - [Usefulness of roentgenological examination in evaluation of the lesser
      circulation].

PMID- 14957617
TI  - [Cardiac aneurysm].

PMID- 14957618
TI  - [Unusual auscultatory phenomenon resulting from and acquired narrowing of the
      main bronchus].

PMID- 14957619
TI  - [Tracing of the interventricular border in bundle branch block by means of the
      electrocardiogram].

PMID- 14957620
TI  - [Determination of incapacity to work due to pulmonary tuberculosis in the open
      treatment facilities].

PMID- 14957621
TI  - [Chronic leukemic reticulosis; cytoimmunology].

PMID- 14957622
TI  - [Pulmonary hypertension].

PMID- 14957623
TI  - [Physical and physiological basis of circulation with a special consideration of
      the action of air-chamber and peripheral resistance].

PMID- 14957624
TI  - [Primary bronchial cancer masked by pleural empyema].

PMID- 14957625
TI  - [Effect of the focus of infection on human physiopathology].

PMID- 14957626
TI  - [Effect of loss of chlorine on secretory activity of the stomach and its clinical
      utilization].

PMID- 14957627
TI  - [Difficulties of diagnosis of circulatory disorders in athletes].

PMID- 14957628
TI  - [Chronic pulmonary suppurative foci as causing factors in nephrosis].

PMID- 14957629
TI  - [A case of diaphragmatic hernia with severe hypochromic anemia].

PMID- 14957630
TI  - [Effect of bile and dehydrocholic acid tuberculin reactions and specific lesions
      in experimental tuberculosis].

PMID- 14957631
TI  - [Atypical syphilitic reactions].

PMID- 14957632
TI  - [Recording of the fetal pulse].

PMID- 14957633
TI  - [Effect of storage of non-coagulating blood in Biernacki's reaction].

PMID- 14957634
TI  - [The latent form of Sturge-Weber disease].

PMID- 14957635
TI  - [Preparation of vitamin B12 concentrates through fermentation].

PMID- 14957636
TI  - [Analysis of electrocardiograms obtained during athletic performance].

PMID- 14957637
TI  - [Report of IV Polish Congress of Rheumatologists in Sopota, 25 and 26 April
      1952].

PMID- 14957638
TI  - [Self-registering absorptiometer for paper electrophoresis of serum proteins].

PMID- 14957639
TI  - [Clinical evaluation of chloromycetin produced in Poland].

PMID- 14957640
TI  - [Experimental psoriasis].

PMID- 14957641
TI  - [Chorionepithelioma of extratesticular origin in men].

PMID- 14957642
TI  - [Perforation of the esophagus and common carotid artery by a bone].

PMID- 14957643
TI  - [Sociological meaning of scrofulous inflammation of the eye].

PMID- 14957644
TI  - [Mitogenetic radiations].

PMID- 14957645
TI  - [Hundred and thirtieth anniversary of the founding of the Warsaw Medical
      Society].

PMID- 14957646
TI  - [Report of the IV Polish Congress of Rheumatologists in Sopota, 25 and 26 April
      1952].

PMID- 14957647
TI  - [Effect of purified protein derivative in a case of tuberculous meningitis with
      spinal block].

PMID- 14957648
TI  - [Controlled hypotension and retropubic prostatectomy; preliminary note].

PMID- 14957649
TI  - [Modern medical treatment of gastroduodenal ulcer].

PMID- 14957650
TI  - [Surgical treatment of vascular diseases of the brain].

PMID- 14957651
TI  - [Effect of cervical sympathectomy on the vasomotor activity of cerebral
      capillaries; experimental study].

PMID- 14957652
TI  - [Superior and inferior cervical sympathectomy and its areas of vasodilatation].

PMID- 14957653
TI  - [Modifications in cerebral and peripheral blood after cervical sympathectomy].

PMID- 14957654
TI  - [Cervical sympathectomy in myocardial infarct and ventricular strain;
      electrocardiography].

PMID- 14957655
TI  - [New observations on glomus tumors].

PMID- 14957656
TI  - [Interpretation of the leukocyte picture in infection].

PMID- 14957657
TI  - [Banti's disease or Banti's syndrome; modern viewpoint].

PMID- 14957658
TI  - [Acute abdomen induced by hemorrhagic metastasis; clinical note].

PMID- 14957659
TI  - The management of scoliosis.

PMID- 14957660
TI  - Some cases of gout.

PMID- 14957661
TI  - Electromyography of the erector spinal in low back pain.

PMID- 14957662
TI  - A case of synovial chondromatosis of the temporo-mandibular joint.

PMID- 14957663
TI  - Osteogenic sarcoma or osteomyelitis; a case report.

PMID- 14957664
TI  - The Judget arthroplasty of the hip via Gibson's lateral approach.

PMID- 14957665
TI  - Clinical assessment of the newer antibiotics.

PMID- 14957666
TI  - Localization of the placenta by means of a radio-active isotope.

PMID- 14957667
TI  - The radiological localization of the placenta.

PMID- 14957668
TI  - Lymphoedema.

PMID- 14957669
TI  - CLINICO-PATHOLOGICAL conference No. 18; diabetic tabes.

PMID- 14957671
TI  - The physiologic approach to the management of itching.

PMID- 14957670
TI  - A new stomach clamp.

PMID- 14957672
TI  - Cortisone and corticotropin in the treatment of cutaneous diseases.

PMID- 14957673
TI  - Management of bacterial infections of the skin.

PMID- 14957674
TI  - Superficial fungous infections.

PMID- 14957675
TI  - The management of acne vulgaris.

PMID- 14957677
TI  - Causes and treatment of urticaria.

PMID- 14957676
TI  - Allergic dermatitis of the hands.

PMID- 14957678
TI  - Treatment of benign tumors of the skin.

PMID- 14957679
TI  - Differential diagnosis and treatment of amenorrhea.

PMID- 14957680
TI  - Impropriety of excessive prostatic massage.

PMID- 14957681
TI  - Treatment of cardiovascular syphilis.

PMID- 14957682
TI  - Abnormal bleeding in childhood.

PMID- 14957683
TI  - Toxoplasmosis in children.

PMID- 14957685
TI  - Surgical intrathoracic cardiovascular lesions.

PMID- 14957684
TI  - The ever-continuing search for immunity in tuberculosis.

PMID- 14957686
TI  - Management of breech presentation.

PMID- 14957687
TI  - Herpes zoster.

PMID- 14957688
TI  - Acute and chronic osteomyelitis.

PMID- 14957689
TI  - Duodenal and gastric ulcer.

PMID- 14957690
TI  - Frigidity in women.

PMID- 14957692
TI  - Some practical aspects of lumbar puncture.

PMID- 14957691
TI  - The cumulative effects of x-ray exposures.

PMID- 14957693
TI  - Medical examination of prostitutes.

PMID- 14957694
TI  - Current use of antibiotics.

PMID- 14957695
TI  - Congenital laryngeal stridor.

PMID- 14957696
TI  - Foot problems in children.

PMID- 14957697
TI  - When he comes ashore.

PMID- 14957698
TI  - The use of virus in human cancer.

PMID- 14957699
TI  - More trouble with British National Health Service.

PMID- 14957700
TI  - Pharmacology in medical progress.

PMID- 14957701
TI  - [Schlieren studies on ultrasonic permeability of the temporal bone].

PMID- 14957702
TI  - Thymus and stridor.

PMID- 14957703
TI  - [A case of tubercular otitis media after oral ingestion of B.C.G..].

PMID- 14957704
TI  - [On primary tuberculosis of the middle ear].

PMID- 14957705
TI  - Spurting salivation in the form of "saliva fountain" from the stenonian and
      whartonian ducts.

PMID- 14957706
TI  - Problem of tonsillectomy; ectomy a chaud combined with penicillin-sulfonamide
      assurance.

PMID- 14957707
TI  - [Goniometry of Romberg's sign and the effects of galvanic vestibular excitation].

PMID- 14957708
TI  - [Surgical treatment of inguinal hernia].

PMID- 14957709
TI  - [Comments on hepatic, biliary, duodeno-pancreatic, and splenic surgery].

PMID- 14957710
TI  - [Mediastinal hemangioendothelioma].

PMID- 14957711
TI  - [Papyraceous monster].

PMID- 14957712
TI  - [Intestinal obstruction treated by Noble's method].

PMID- 14957713
TI  - [Tuberculous pleurisy and posterior mediastinal tumor in the same hemithorax].

PMID- 14957714
TI  - [Ovarian fibromyxoma].

PMID- 14957715
TI  - [Chronic gouty arthritis].

PMID- 14957716
TI  - [The cervical rib; symptoms; differential diagnosis; and indications for
      scalenotomy].

PMID- 14957717
TI  - [Plasma cell myeloma or Kohler's disease].

PMID- 14957718
TI  - [Scattered cerebellar symptomatology; diagnostic significance].

PMID- 14957719
TI  - [Hormonal changes in a case of myeloblastic leukemia with massive bilateral
      testicular infiltration].

PMID- 14957720
TI  - [Sinoauricular block with Morgagni-Stokes-Adams syndrome caused by streptomycin].

PMID- 14957721
TI  - [Aerosol therapy with combined drugs].

PMID- 14957722
TI  - [Surgical treatment of flatfoot in adolescents; physiopathological concepts].

PMID- 14957723
TI  - [Arm support and instrument holder for surgery and anesthesia].

PMID- 14957724
TI  - [Castillo Odena's operating table; universal model].

PMID- 14957725
TI  - [Liver function tests; Bauer's galactose test].

PMID- 14957726
TI  - [Study on allergic rheumatic diseases].

PMID- 14957727
TI  - [Effect of associated sodium citrate and sodium phosphate with nicotinic acid in
      certain peripheral vascular diseases].

PMID- 14957728
TI  - [Chronic infiltrative segmental colitis].

PMID- 14957729
TI  - [Inflammatory stenosis of the common bile duct].

PMID- 14957730
TI  - [Radiological visualization of the thoracic duct].

PMID- 14957731
TI  - [Subclavioaxillary double aneurysm].

PMID- 14957732
TI  - [Hammer toe; Hohmann's operation].

PMID- 14957733
TI  - [Ion exchange resins in the treatment of edemas].

PMID- 14957734
TI  - [Blood disease of difficult classification].

PMID- 14957735
TI  - [Cephalgias].

PMID- 14957736
TI  - [Present aspects of duodenal catheterization; choledochoduodenal drainage test
      and its significance and clinical and surgical diagnosis].

PMID- 14957737
TI  - [Considerations on a tuberculostatic agent, ketocholanic acid thiocarbamic
      hydrazone].

PMID- 14957738
TI  - [Olier's and Poncet's periostitis albuminosa].

PMID- 14957739
TI  - [Treatment of fractures of the flat surfaces of the tibia].

PMID- 14957740
TI  - [Respiratory rehabilitation in Heine Medin disease].

PMID- 14957741
TI  - [Subungual exostosis].

PMID- 14957742
TI  - [Present concept of mercurial diuretics].

PMID- 14957743
TI  - [Pathogenesis of neurogenous arterial hypertension].

PMID- 14957744
TI  - [Minimal syndrome in rheumatoid arthritis].

PMID- 14957745
TI  - [Therapy of benign diseases of the breast].

PMID- 14957746
TI  - [Results of subcutaneous mercurial diuretics].

PMID- 14957747
TI  - [Treatment of residual and recurrent dyspepsias].

PMID- 14957748
TI  - [Treatment of herpes zoster with chloramphenicol].

PMID- 14957749
TI  - [Paraaminobenzoyl-diethylamino-ethanol hydrochloride in general anesthesia].

PMID- 14957750
TI  - [Iliopubic band].

PMID- 14957751
TI  - [Fractures and dislocation of the forearm and the wrist].

PMID- 14957752
TI  - [Function of amino acids in therapy].

PMID- 14957753
TI  - [Differential diagnosis of generalized osteopathies].

PMID- 14957754
TI  - [Epistaxis; etiophysiopathogenesis].

PMID- 14957755
TI  - [Protective effect of isonicotinic acid hydrazide in experimental tuberculosis in
      guinea pig].

PMID- 14957756
TI  - [Gastric function test with iodine salts].

PMID- 14957757
TI  - [Appendiceal carcinoid].

PMID- 14957758
TI  - [Herpes simplex; certain problems presented by the study of its virus].

PMID- 14957759
TI  - [Cardiac insufficiency].

PMID- 14957760
TI  - [Liver function test; Quick's test with hippuric acid].

PMID- 14957761
TI  - [Effect of globin in acid solution on chronic pulmonary tuberculosis; clinical
      and radiologic results].

PMID- 14957762
TI  - [Parotitis and reflex submaxillitis].

PMID- 14957763
TI  - [Acute disseminated lupus erythematosus; clinical picture and nosographic
      considerations, collagen diseases, lupus erythematosus cells, lupus erythematosus
      phenomenon, Haserick's globulin].

PMID- 14957764
TI  - [Allergic diseases as diseases of general adaptation syndrome].

PMID- 14957765
TI  - [Congenital hematogenous multifocal pneumonia in newborn].

PMID- 14957766
TI  - [Right aortic arch].

PMID- 14957767
TI  - [Fractures and dislocation of the shoulder and of the arm].

PMID- 14957768
TI  - [Clinicopathological conference of the Instituto de semiologia Gregorio Aroaoz
      Alfaro; recurrent active chronic nephritis with congestive cardiac
      insufficiency].

PMID- 14957769
TI  - [Clinical study on congenital heart diseases].

PMID- 14957770
TI  - [Tumors of the small intestine; radiological diagnosis].

PMID- 14957771
TI  - [Treatment of bronchial asthma with banthine].

PMID- 14957772
TI  - [Recurrent acute agranulocytosis].

PMID- 14957773
TI  - [Transfusion, perfusion; Bartola's bottle holder].

PMID- 14957774
TI  - [Wounds and injuries, and surgery of lower extremities].

PMID- 14957775
TI  - [Study on origins of neurosis].

PMID- 14957777
TI  - [Surgical treatment of gastroduodenal ulcer].

PMID- 14957776
TI  - [Studies on a group of Coxsackie viruses and their relation to poliomyelitis].

PMID- 14957778
TI  - [Differential diagnosis of epileptic crisis from similar non-epileptic
      conditions].

PMID- 14957779
TI  - [Clinico-pathological conference; biliary carcinoma].

PMID- 14957780
TI  - [Problems relative to pinta, yaws, and bejel].

PMID- 14957781
TI  - [Diagnosis of tumors of the colon and rectum; review].

PMID- 14957782
TI  - [Mexican Amblyomma castanedai n. sp. (Ixodidae)].

PMID- 14957783
TI  - [Modernization of methods].

PMID- 14957784
TI  - [New remedies for arterial hypertension].

PMID- 14957785
TI  - [Clinico-pathological conference; generalized acute peritonitis].

PMID- 14957786
TI  - [Acute miliary tuberculosis and purpura].

PMID- 14957787
TI  - [Functional biliary dystonia. Role of the right pneumogastric nerve; experimental
      study and surgical inferences].

PMID- 14957788
TI  - [Supra-renal anuria].

PMID- 14957789
TI  - [On the excitability of the sympathetic. Effect of some quaternary ammonium
      compounds].

PMID- 14957790
TI  - [A new vegetative stabilizer; 4560 R.P..].

PMID- 14957791
TI  - [Second Antarctic Expedition to Adelia Land].

PMID- 14957792
TI  - [Cranio-meningeal pain, of traumatic origin, with a local point of departure and
      surgically curable].

PMID- 14957793
TI  - [Evaluation of urinary corticoids].

PMID- 14957794
TI  - [On sero-fibrinous pleurisy presumed to be tuberculous].

PMID- 14957795
TI  - [Fatal evolution of a hemiplegia].

PMID- 14957796
TI  - [Choledochoduodenostomy without abandoned prosthesis].

PMID- 14957797
TI  - [Laws of occurrence of eosinophilia in animal parasitoses].

PMID- 14957798
TI  - [Human tuberculosis of bovine origin].

PMID- 14957799
TI  - [The death of La Dauphine, 1445].

PMID- 14957800
TI  - [An attempt at smallpox vaccination with formol vaccine].

PMID- 14957801
TI  - [Pathogenic mechanism of postoperative pneumopathy].

PMID- 14957802
TI  - [Hepato-serology].

PMID- 14957803
TI  - [Phlebitis of the inferior vena cava, a clinical and experimental study].

PMID- 14957804
TI  - [Biological survey of anticoagulant therapy].

PMID- 14957805
TI  - [Therapy of Hodgkin's disease].

PMID- 14957806
TI  - [The tests of permeability of surgical anastomosis of the portal and caval
      systems].

PMID- 14957807
TI  - [The problem of cancer of the cervix uteri at the zero stage].

PMID- 14957808
TI  - [On the recent cases of smallpox in Marseilles].

PMID- 14957809
TI  - [The affair of the necklace on the allergic cartesian].

PMID- 14957810
TI  - [Pure velum-pharyngeal form of poliomyelitis].

PMID- 14957811
TI  - [New Geneva conventions].

PMID- 14957812
TI  - [Pierre Rouques, 1900-1952].

PMID- 14957813
TI  - [Ehrlichin: non-bacteriostatic and non-microbicide antibiotic but clearly
      virulicide].

PMID- 14957814
TI  - [A very late, complex deficiency syndrome in a gastrectomized patient].

PMID- 14957815
TI  - [Hydrazine derivatives of isonicotinic acid in the treatment of experimental and
      human tuberculosis].

PMID- 14957816
TI  - [Fahr's disease; idiopathic non-arteriosclerotic intracerebral calcification and
      its relation to tetany].

PMID- 14957817
TI  - [Biopies of the pancreas].

PMID- 14957818
TI  - [The early diagnosis of uterine cancer].

PMID- 14957819
TI  - [On urethritis due to Trichomonas vaginalis in man].

PMID- 14957820
TI  - [Nonspecific acute pericarditis].

PMID- 14957821
TI  - [Latent esophagitis].

PMID- 14957822
TI  - [How and when cortisone should be used in ophthalmology].

PMID- 14957823
TI  - [Ankylosing operations of the spine].

PMID- 14957824
TI  - [Effective salicyl-therapy in Bouillaud's disease].

PMID- 14957826
TI  - [Swine fever or erysipeloid of Rosenbach].

PMID- 14957825
TI  - [Human tuberculosis of bovine origin].

PMID- 14957827
TI  - [Leukorrhea].

PMID- 14957828
TI  - [New Geneva Conventions].

PMID- 14957829
TI  - [Experimental research on a synthetic ganglioplegic].

PMID- 14957830
TI  - [Genoneurodermatoses].

PMID- 14957831
TI  - [Retinal and cerebral circulation].

PMID- 14957832
TI  - [Resistance of tubercle bacilli to isonicotinic hydrazide].

PMID- 14957833
TI  - [Action of choline chloride in the course of some hepatic diseases].

PMID- 14957834
TI  - [Dangers of using hexamethonium in medicine and surgery].

PMID- 14957835
TI  - [Two cases of xeroderma pigmentosum ameliorated by cortisone].

PMID- 14957836
TI  - [Benign tumors of the stomach].

PMID- 14957837
TI  - [Something new on Claude Bernard; two unpublished manuscripts].

PMID- 14957838
TI  - [Tuberculosis in psychical patients].

PMID- 14957839
TI  - [Application of therapeutic sleep in pulmonary tuberculosis in thoracic surgery].

PMID- 14957840
TI  - [Sources of hemorrhage and suppurations following pneumonolysis].

PMID- 14957841
TI  - [Modified extended thoracoplasty with pneumonolysis and fixation of the apex].

PMID- 14957842
TI  - [Result of the application of paravertebral novocaine block with methylene blue
      as adjunct in thoracocautery].

PMID- 14957843
TI  - [Surgical treatment of pulmonary tuberculosis in a district hospital].

PMID- 14957844
TI  - [Cavernous contents].

PMID- 14957845
TI  - [Tuberculous cavern and its development; tomographic findings].

PMID- 14957846
TI  - [Significance of kymographic investigation of the lungs in the study of the
      mechanism of phrenicectomy].

PMID- 14957847
TI  - [Experimental tuberculosis of the bone].

PMID- 14957848
TI  - [Result of activities of the Moscow District Society for Prevention of
      Tuberculosis].

PMID- 14957849
TI  - [Exposure of virulence in sanatoria for latent forms of tuberculosis].

PMID- 14957850
TI  - [Measurement of pleural adhesions in thoracoscopy].

PMID- 14957851
TI  - [Rapid method of determination of streptomycin resistance in Mycobacterium
      tuberculosis].

PMID- 14957852
TI  - DISCUSSION on the thermodynamics of elasticity in biological tissues.

PMID- 14957853
TI  - The thermodynamics of elasticity in resting striated muscle.

PMID- 14957854
TI  - Thermoelastic properties of several biological systems.

PMID- 14957856
TI  - Is the contracting muscle in a new elastic equilibrium?

PMID- 14957855
TI  - The thermodynamic study of rubber-like elasticity.

PMID- 14957857
TI  - A factor modifying the shortening response of muscle fiber bundles to ATP.

PMID- 14957858
TI  - Infra-red spectra of muscle.

PMID- 14957860
TI  - Minimum areas and leaf determination.

PMID- 14957859
TI  - The effects of carbohydrate and sea water on the metabolism of men without food
      or sufficient water.

PMID- 14957861
TI  - Selective and non-selective admission of various antitoxins into foetal rabbits.

PMID- 14957862
TI  - An investigation of some adaptive changes in yeast cells.

PMID- 14957863
TI  - Body water and electrolytes in acute anhydraemia.

PMID- 14957864
TI  - Early changes in degenerating mammalian nerves.

PMID- 14957865
TI  - Post-partum genital tuberculosis.

PMID- 14957866
TI  - Toxaemic accidental haemorrhage observations on its etiology, phases and
      treatment.

PMID- 14957867
TI  - Some features of placental and decidual vessels in relationship to toxaemic
      accidental haemorrhage.

PMID- 14957868
TI  - The retinal vessels in hypertensive disease.

PMID- 14957869
TI  - The theoretical basis of neurosurgical anaesthesia.

PMID- 14957870
TI  - PRESENT position of anaesthesia for neurosurgery.

PMID- 14957871
TI  - The practical aspects of neurosurgical anaesthesia.

PMID- 14957872
TI  - William Cole (1635-1716) and his discovery of the spiral nature of the intestinal
      musculature.

PMID- 14957873
TI  - Green teeth in baby due to rhesus incompatibility.

PMID- 14957874
TI  - Thoracic inlet syndrome with recurrence of symptoms after operation.

PMID- 14957875
TI  - Malignant hypertension in a girl of 16.

PMID- 14957876
TI  - Case of diagnosis: chronic pancreatitis.

PMID- 14957877
TI  - Discussion on the role of the psychologist in psychiatric practice.

PMID- 14957878
TI  - Dystonia musculorum deformans in siblings; treated with artane (trihexyphenidyl).

PMID- 14957879
TI  - Fanconi syndrome in two siblings.

PMID- 14957880
TI  - Congenital partial heart block.

PMID- 14957881
TI  - An epidemic follicular eruption.

PMID- 14957882
TI  - Carcinoma erysipelatodes.

PMID- 14957883
TI  - Febrile, relapsing, nodular, non-suppurative panniculitis (Weber-Christian).

PMID- 14957884
TI  - Discussion: health its study and culture in the nation today.

PMID- 14957885
TI  - DISCUSSION: acid-fast bacilli cultivation and diagnostic procedures.

PMID- 14957886
TI  - Acid-fast bacilli cultivation.

PMID- 14957887
TI  - The serodiagnosis of tuberculosis.

PMID- 14957888
TI  - Bovine mastitis resembling tuberculosis caused by rapidly growing acid-fast
      bacteria.

PMID- 14957889
TI  - Complement-fixation tests and the mycobacteria infections.

PMID- 14957890
TI  - Pulmonary resection for tuberculosis: a review of 73 cases with a follow-up of
      one year or longer.

PMID- 14957891
TI  - Experimental procedures designed to increase the blood supply to the myocardium.

PMID- 14957892
TI  - Surgical treatment of mitral stenosis.

PMID- 14957893
TI  - Cardiac clinics. CXXXIX. Myxoma of the left atrium clinically simulating mitral
      stenosis: report of case and pathologic studies.

PMID- 14957894
TI  - An aid to the induction of general anesthesia in young children.

PMID- 14957895
TI  - Effect of isonicotinic acid hydrazide (isoniazid) on survival time of mice
      infected with tubercle bacilli resistant to the drug in vitro.

PMID- 14957896
TI  - [Cardioactive heterosides and adrenal cortex hormones].

PMID- 14957897
TI  - [Antibiotics produced by Actinomyces].

PMID- 14957898
TI  - [Synthetic estrogens].

PMID- 14957899
TI  - [Some present-day problems of hygiene and public health. II. Some current-aspects
      of cancer research].

PMID- 14957900
TI  - [Impressions of a trip to Colombia and Venezuela].

PMID- 14957901
TI  - [Relation between chemical structure and antibacterial activity].

PMID- 14957902
TI  - [Present-day pharmaceutical products extracted from the Apocynaceae; alkaloids
      and heterosides].

PMID- 14957903
TI  - [Importation of pharmaceutical products by Norway].

PMID- 14957904
TI  - [Some present-day problems of hygiene and public health. III. Problems in
      toxicology and industrial hygiene].

PMID- 14957905
TI  - [Relation between chemical structure and antibacterial activity].

PMID- 14957906
TI  - [Medicaments and the pharmaceutical form in which they appear].

PMID- 14957907
TI  - [Organic synthesis, creator of drugs].

PMID- 14957908
TI  - [The role of pharmacodynamics in the orientation of therapeutic research].

PMID- 14957909
TI  - [Some considerations on the antibiotics].

PMID- 14957910
TI  - [The control of drugs].

PMID- 14957911
TI  - [Modern industrial pharmaceutical apparatus].

PMID- 14957912
TI  - [Industrial legislation in the Code of Pharmacy].

PMID- 14957914
TI  - [French pharmaceutical laboratories].

PMID- 14957913
TI  - [The organization and expansion of the French pharmaceutical industry].

PMID- 14957915
TI  - [Folic acid].

PMID- 14957917
TI  - [The International Pharmacopeia].

PMID- 14957916
TI  - [The active principles of some hepatorenal diuretics: glycollic acid and glyceric
      acid].

PMID- 14957919
TI  - [Folic acid].

PMID- 14957918
TI  - [Isoniazid, a new chemotherapeutic agent (isonicotinyl hydrazide)].

PMID- 14957920
TI  - [Chemical structure and local anesthetic activity].

PMID- 14957921
TI  - [Some present-day problems of hygiene and public health. IV. Methods of treating
      water supplies for human consumption].

PMID- 14957922
TI  - [Advances of modern urology].

PMID- 14957923
TI  - [Evaluation of modern antituberculosis chemotherapeutics].

PMID- 14957924
TI  - [Effect of heparin on albumin level of blood plasma and serum].

PMID- 14957925
TI  - [Nitrogranulogen in treatment of inflammatory diseases of the reproductive
      system].

PMID- 14957927
TI  - [Case of cancer of the nipple].

PMID- 14957926
TI  - [Mineral components of drinking water and goiter in district of Myslenice].

PMID- 14957928
TI  - [Arterial blood pressure in hypertension complicated by adrenal cortex
      insufficiency].

PMID- 14957930
TI  - [Errors in diagnosis and treatment of eye diseases].

PMID- 14957929
TI  - [New paths in endocrinology].

PMID- 14957931
TI  - [Arrested developmental processes].

PMID- 14957932
TI  - [Criticism of chromosome theory of heredity based on studies of early periods of
      ontogenesis].

PMID- 14957933
TI  - [Effect of mitotic poisons on growth and regeneration].

PMID- 14957935
TI  - [Stimulation of further development in embryos arrested in critical stages].

PMID- 14957934
TI  - [Effect of injected cholesterol on gonad chemistry of a white rat].

PMID- 14957936
TI  - [Effect of the mercury vapor lamp on growth and development of tadpoles of Rana
      temporaria L].

PMID- 14957937
TI  - [Nucleic acids in endocrine glands. Part II. Ovaries].

PMID- 14957939
TI  - [Traumatic lithiasis].

PMID- 14957938
TI  - [Effect of typhoid toxin on ovaries].

PMID- 14957940
TI  - [Cadmium test in evaluation of the extent of liver parenchyma injury].

PMID- 14957941
TI  - [Effect of combined nitrogen mustard and small doses of streptomycin on spinal
      tuberculosis with paraplegia].

PMID- 14957942
TI  - [Examination of sound intensity equalization by means of aural harmonic tones].

PMID- 14957943
TI  - [A case of Majocchi's annular purpura].

PMID- 14957944
TI  - [Effect of methylthiouracil on the function of reproductive system in laboratory
      animals].

PMID- 14957945
TI  - [Lymphopenic reaction as tests of adrenal function].

PMID- 14957946
TI  - [Effect of ether anesthesia on estrus in mice].

PMID- 14957947
TI  - [The Oedipus complex is not a complex].

PMID- 14957948
TI  - [The universe of guilt; reflections on the bases of intellectual Stalinism in
      Europe].

PMID- 14957949
TI  - [Attitude of Soviet psychologists toward tests].

PMID- 14957950
TI  - [The sexual reflex of raised arms in women].

PMID- 14957951
TI  - [Father and son: clinical case report].

PMID- 14957952
TI  - [Problem of aggressivity in boys; case history].

PMID- 14957953
TI  - [Morphopsychology in employee selection].

PMID- 14957954
TI  - [National Association of Psychoanalysts].

PMID- 14957955
TI  - [Beyond 19th century materialism].

PMID- 14957956
TI  - [Father and son: a clinical case report].

PMID- 14957957
TI  - [The fairies in A la Recherche du Temps Perdu; introduction to the Proustian
      myths].

PMID- 14957958
TI  - [Circumcision among the Jews; possible explanation as attenuated castration
      inflicted upon the sons by the chief of the tribe].

PMID- 14957959
TI  - [Morphopsychology in industrial psychology].

PMID- 14957960
TI  - [The scientific achievement of Paul Federn; in his memory].

PMID- 14957961
TI  - [Analysis of existence in psychology and psychiatry].

PMID- 14957962
TI  - [Necessity of reduction of the psychology of the unconscious to its scientific
      basis].

PMID- 14957963
TI  - [A conflict situation caused by separation].

PMID- 14957964
TI  - [Recent advances of psychotherapy in psychosomatic medicine].

PMID- 14957965
TI  - [Organ psychosis in psychosomatic medicine].

PMID- 14957966
TI  - [Authority and onanism].

PMID- 14957967
TI  - Preventive psychiatry; with particular reference to children.

PMID- 14957968
TI  - Statistical and other arguments for and against cancer education.

PMID- 14957969
TI  - Estimates of disabling illness prevalence in the United States; based on the
      current population survey of February 1949 and September 1950.

PMID- 14957970
TI  - [Observations on the use of desoxycorticosterone acetate in labor].

PMID- 14957971
TI  - [Recent progress in the treatment of vomiting in pregnancy and radiation
      sickness].

PMID- 14957972
TI  - [Blood protein changes in uterine and vaginal neoplasms treated with radium and
      roentgen rays].

PMID- 14957973
TI  - [Clinical and experimental study on urinary 17-ketosteroids; age and sex
      factors].

PMID- 14957974
TI  - Experience with the new anticoagulant phenylindanedione in acute myocardial
      infarction; preliminary report of 50 cases.

PMID- 14957975
TI  - Decidual reaction in the ovary.

PMID- 14957976
TI  - Lymphosarcoma of the stomach; the value of gastroscopy in diagnosis.

PMID- 14957977
TI  - Tumors of the spinal cord. I. Intramedullary tumors.

PMID- 14957978
TI  - The treatment of uremia by dialysis across the intestinal mucosa.

PMID- 14957979
TI  - The cervical sympathetic ganglia: an anatomical study of 100 cervicothoracic
      dissections.

PMID- 14957980
TI  - What are the poliomyelitis viruses?

PMID- 14957981
TI  - The etiology and pathogenesis of congenital megacolon.

PMID- 14957982
TI  - Variations in the form and attachments of the biceps brachii muscle.

PMID- 14957983
TI  - CLINICAL pathological conferences of Northwestern University Medical School:
      primary splenic vein thrombosis with complications.

PMID- 14957984
TI  - The Rheumatic Fever Research Institute, Northwestern University Medical School.

PMID- 14957985
TI  - The Department of Medicine, Northwestern University Medical School.

PMID- 14957986
TI  - Vignettes mediterraneenes. XXIII. Repple depple.

PMID- 14957987
TI  - "The infantry--they got everything".

PMID- 14957988
TI  - A tribute to Archibald Church, March 23, 1861-May 8, 1952.

PMID- 14957989
TI  - A tribute to Theodore Thaddeus Stone, August 3, 1897-March 5, 1952.

PMID- 14957990
TI  - RECENT publications of Northwestern University Medical School faculty.

PMID- 14957991
TI  - Hypopituitarism in male subjects due to syphilis, with a discussion of androgen
      treatment.

PMID- 14957992
TI  - Tumours involving the brain-stem; a study of 90 cases arising in the brain-stem,
      fourth ventricle, and pineal tissue.

PMID- 14957993
TI  - Acute infectious lymphocytosis.

PMID- 14957994
TI  - The pulmonary complications of influenza as seen in Sheffield in 1949.

PMID- 14957995
TI  - The effect of corticotrophin in rheumatic fever.

PMID- 14957996
TI  - Follicular lymphoma.

PMID- 14957997
TI  - Lymphangitis carcinomatosa of the lungs.

PMID- 14957998
TI  - [Angiopneumography in differential diagnosis of tumor from pulmonary abscess].

PMID- 14957999
TI  - [Precoccygeal insufflation of the anterior and posterior mediastinum].

PMID- 14958000
TI  - [Functional factors in urography].

PMID- 14958001
TI  - [Morphological variations of the distal epiphysis of the humerus].

PMID- 14958002
TI  - [Studies on a method of radiologic pelvimetry].

PMID- 14958004
TI  - [Radiological picture and surgical and anatomo-pathological aspects of a case of
      gastric polypi].

PMID- 14958003
TI  - [Radiologic diagnosis of 70 cases of spinal tumors].

PMID- 14958005
TI  - [Extraperitoneal pneumoabdomen and stratigraphy in cholecystography].

PMID- 14958006
TI  - [Studies on the treatment of tonsillar epitheliomas and adenopathies with
      roentgen rays alone].

PMID- 14958007
TI  - [Attempted photometry of skeletal radiographic density].

PMID- 14958008
TI  - [Metrorrhagia in puberty and radiologic picture of the sellar region and of
      sphenoid sinuses].

PMID- 14958009
TI  - Chronic gastritis; a review of the literature.

PMID- 14958010
TI  - Antral gastritis.

PMID- 14958011
TI  - Roentgenologic exploration of gastric rugae with reference to the diagnosis of
      gastritis.

PMID- 14958012
TI  - Speculations concerning the probable evolution of chronic gastritis.

PMID- 14958013
TI  - Clinical aspects of gastritis and the gastroscopic findings.

PMID- 14958014
TI  - Difficulties in the differential diagnosis of gastric carcinoma and gastritis;
      surgical considerations.

PMID- 14958015
TI  - Pathology of gastritis.

PMID- 14958016
TI  - Problem of pathogenesis of chronic hypertrophic gastritis.

PMID- 14958017
TI  - Calcifying tendinitis of the shoulder; a critical study of the value of x-ray
      therapy.

PMID- 14958018
TI  - Results of radiation therapy for bronchogenic carcinoma; a statistical analysis
      of 125 cases.

PMID- 14958019
TI  - Experience with grid therapy.

PMID- 14958020
TI  - Adenoma of the jejunum; a case report.

PMID- 14958021
TI  - Calcinosis universalis; with report of a case.

PMID- 14958022
TI  - Preoperative roentgen demonstration of non-opaque foreign body in the duodenum;
      report of a case.

PMID- 14958023
TI  - Pseudo-albuminuria following monophen and priodax.

PMID- 14958024
TI  - REFRESHER courses: postgraduate instruction.

PMID- 14958025
TI  - RADIOLOGICAL societies: secretaries and meeting dates.

PMID- 14958026
TI  - [Local application of chloramphenicol in ocular infections].

PMID- 14958027
TI  - [Topical use of chloramphenicol in dermatology with special reference to its
      cicatrizing effect].

PMID- 14958028
TI  - [Case of confusional psychosis onset during chloramphenicol therapy of typhoid
      fever and spontaneous regression without suspension of treatment].

PMID- 14958029
TI  - [Mediterranean exanthematous fever and antibiotics].

PMID- 14958030
TI  - [Bronchoscopic and bronchographic findings in silicosis].

PMID- 14958031
TI  - [Prevention of accidents in epilepsy].

PMID- 14958032
TI  - [Artificial illumination in industry].

PMID- 14958033
TI  - [Possibility of multiple screening in examining for asbestosis and silicosis in
      workers].

PMID- 14958034
TI  - [Axillary thrombophlebitis syndromes due to physical stress; clinical,
      hygienical, and preventive aspects].

PMID- 14958035
TI  - [Pathological conditions and sanitary assistance to phosphate miners in
      Khouribgha in French Marocco].

PMID- 14958036
TI  - [Observations on the masticatory apparatus in caisson disease].

PMID- 14958037
TI  - [Effect of beryllium oxide on hematological changes; experimental study].

PMID- 14958038
TI  - [Ferruccio Banissoni (Triest, September 29, 1888 - Rome, April 27, 1952)].

PMID- 14958039
TI  - [A case of myelogenous progressive muscular atrophy; clinical and anatomo
      pathological observations].

PMID- 14958040
TI  - [Psychosurgery and criminality].

PMID- 14958041
TI  - [Effect of the spinal fluid of mental patients before and after shock on
      experimental catatonia].

PMID- 14958042
TI  - [Glossopharyngeal neuralgia].

PMID- 14958043
TI  - [Applications of psychiatry: legal].

PMID- 14958044
TI  - [General adaptation syndrome and shock therapy in mental diseases].

PMID- 14958045
TI  - [Psychopathological and social genesis of juvenile delinquency in normal
      subjects].

PMID- 14958046
TI  - [Reform of legislation on psychiatric hospitals and the insane; possibilities of
      a medical law].

PMID- 14958047
TI  - [Report of the Special Commission on the study of modern scientific methods of
      research on truth and personality and their eventual adoption in forensic
      practice].

PMID- 14958048
TI  - [Convulsive threshold in relation to multiple sensory stimuli of variable
      frequency and intensity].

PMID- 14958049
TI  - [A Gestalt test (task interruption and task completion tests) applied to senile
      psychopathology].

PMID- 14958050
TI  - [Clinical psychoanalysis of the prepsychotic personality in schizophrenia].

PMID- 14958051
TI  - [Behavior of blood cholesterol in electronarcosis].

PMID- 14958052
TI  - [Behavior of urinary elimination of 17-ketosteroids in mental patients treated
      with convulsive therapy].

PMID- 14958053
TI  - [Bibliotherapy].

PMID- 14958054
TI  - [First therapeutic results with antireticular cytotoxic serum (Citolisina Sclavo)
      in schizophrenia and presenile psychoses].

PMID- 14958055
TI  - [Treatment of epileptic psychoses by vegetative block (Bolsi technic)].

PMID- 14958056
TI  - [In commemoration of Giuseppe Corberi].

PMID- 14958057
TI  - [Giuseppe Pellacani, 1886-1952].

PMID- 14958058
TI  - [National congress of the Association of Italian Psychiatric Hospital
      Physicians].

PMID- 14958059
TI  - [Result of acceleration of circulation of aqueous solution of refrigerants in
      absorption].

PMID- 14958060
TI  - [Quantitative determination of dieldrin].

PMID- 14958061
TI  - [Stylocephalus (Gregarinida) parasites of Tenebrionidae (Blaps); method of
      study].

PMID- 14958062
TI  - [Effect of estrogens on experimental changes in choledystitis and reactions of
      the bile in rabbits].

PMID- 14958063
TI  - [Diphtheria in Italy in 1937-48; second note].

PMID- 14958064
TI  - [Determination of an active bacteriophage on Bacillus megatherium by means of
      electron microscopy and x-rays].

PMID- 14958065
TI  - [Band of oscillation in the spectrum of absorption of ultraviolet rays].

PMID- 14958066
TI  - [Fluorescence excited by alpha particles in stilbene].

PMID- 14958067
TI  - [A generator of rectangular impulses ranging in duration from 0.2 to 10 mu
      seconds].

PMID- 14958068
TI  - [Apparatus for purification of neutron counters with boron trifluoride].

PMID- 14958069
TI  - [Epidemiological studies on cutaneous leishmaniasis in Abruzzo and experience
      with total interruption of transmission (1948-50)].

PMID- 14958070
TI  - [Antibiotics and formaldehyde treated antigens in the production of Brucella
      agglutining sera].

PMID- 14958071
TI  - [Experimental infection of sheep with Coxiella burnetii].

PMID- 14958072
TI  - [Experimental and natural infection with Coxiella burnetii in fowl].

PMID- 14958073
TI  - [Viremia in Heine-Medin disease].

PMID- 14958074
TI  - [Electron microscopy of the blood in mice infected with poliomyelitis virus type
      Lansing].

PMID- 14958075
TI  - [Electron microscopy of the blood from Rhesus monkeys infected with poliomyelitis
      virus type Lansing].

PMID- 14958076
TI  - [Current knowledge on Q fever].

PMID- 14958077
TI  - [Nutritive value of corn mixed with milk].

PMID- 14958078
TI  - [Etiopathogenesis of toxicoses of parenteral origin].

PMID- 14958079
TI  - Refractory peptic ulcer.

PMID- 14958080
TI  - The indications for vagotomy in the surgical treatment of the patient with
      chronic peptic ulcer which has failed to respond to medical management.

PMID- 14958081
TI  - The reliability of roentgenographic diagnosis in gastrointestinal disease.

PMID- 14958082
TI  - Anorectal fistula.

PMID- 14958083
TI  - The treatment of diarrheal syndrome with resion.

PMID- 14958084
TI  - Auscultation of the esophagus.

PMID- 14958085
TI  - [Cervical cancer and the Schauta operation].

PMID- 14958086
TI  - [Pulmonary function tests].

PMID- 14958087
TI  - [Commissurotomy in mitral stenosis; 2 successful surgical cases].

PMID- 14958088
TI  - [Surgical technic in inguinal hernia].

PMID- 14958089
TI  - [Immediate gastrectomy in perforated gastric ulcers; 30 surgical cases].

PMID- 14958090
TI  - [Streptokinase and streptodornase: its use in hemothorax following extrapleural
      pneumothorax].

PMID- 14958091
TI  - [The teeth and focal infection].

PMID- 14958092
TI  - [Local treatment of dental care caries].

PMID- 14958094
TI  - [Cancer and its oral manifestations].

PMID- 14958093
TI  - [Biology and prosthesis].

PMID- 14958095
TI  - [Study centers and their cultural significance].

PMID- 14958096
TI  - [The problem of allergy and resistance in tuberculosis].

PMID- 14958097
TI  - [Acute manifestations of retinopathies].

PMID- 14958098
TI  - [Various aspects of the pathology of retinal vessels; anatomophysiological and
      histopathological data].

PMID- 14958099
TI  - [Diabetic retinosis].

PMID- 14958100
TI  - [Edema and exudates in retinopathies].

PMID- 14958101
TI  - [Ocular pemphigus].

PMID- 14958102
TI  - [Reiter's disease].

PMID- 14958104
TI  - [Aniridia].

PMID- 14958103
TI  - [Atrophy of the iris].

PMID- 14958105
TI  - [Adie syndrome].

PMID- 14958106
TI  - [Post mortem pupillary reactions].

PMID- 14958107
TI  - [Assays of collyria].

PMID- 14958108
TI  - [The pupil and collyria].

PMID- 14958109
TI  - [Orthoptics; new methods for the ophthalmologist's solution of many clinical
      problems].

PMID- 14958110
TI  - [Strabismus and heredity].

PMID- 14958111
TI  - [Vertical deviations of the eye].

PMID- 14958113
TI  - [The ophthalmic branch of the trigeminal nerve].

PMID- 14958112
TI  - [Glaucoma and the thyroid].

PMID- 14958114
TI  - [Results of sympathectomy in 110 cases of Meniere's disease].

PMID- 14958115
TI  - [Clinically benign bronchial epitheliomas (Jackson's adenoma)].

PMID- 14958116
TI  - [Mucocele of the maxillary sinus].

PMID- 14958117
TI  - [Malignant melanoma and chondroma of the maxilla].

PMID- 14958118
TI  - [Charles Mollica].

PMID- 14958119
TI  - [Tuberculosis mortality in capital cities of Brazil in the last two decades].

PMID- 14958120
TI  - [Carriers of minimal shadows and work capacity].

PMID- 14958121
TI  - [Treatment of tuberculosis in leprosy; pulmonary tuberculosis mortality in
      Curupaiti; mortality, morbidity and prevention of tuberculosis in lepers].

PMID- 14958122
TI  - [Statistical analysis of dispensary data].

PMID- 14958123
TI  - [Present status of isonicotinic acid hydrazide in the treatment of tuberculosis].

PMID- 14958124
TI  - [Kahn's universal reaction in tuberculosis].

PMID- 14958125
TI  - [Histoplasmosis in children].

PMID- 14958126
TI  - [Angiocardiography in a child].

PMID- 14958127
TI  - [Cardiovascular study in glomerulonephritis in a child with special reference to
      nephritic lung].

PMID- 14958128
TI  - [Activities of the International American Institute for Child Protection].

PMID- 14958129
TI  - [Experiments on surgical anastomosis of arteries].

PMID- 14958130
TI  - [Campaign against Chagas disease in Brazil].

PMID- 14958131
TI  - [New method for the prognostic evaluation of data on blood sedimentation].

PMID- 14958132
TI  - [Abdominal pregnancy].

PMID- 14958133
TI  - [Abdominal pregnancy].

PMID- 14958134
TI  - [Primary ovarian pregnancy].

PMID- 14958135
TI  - [Guterman reaction; preliminary note].

PMID- 14958136
TI  - [Fibroma of the vulva: molluscum pendulum].

PMID- 14958137
TI  - [Diagnosis and therapy of tubal obstruction by insufflation (Rubin test)].

PMID- 14958138
TI  - [The true status of exfoliative cytology].

PMID- 14958139
TI  - [Dysmenorrhea].

PMID- 14958140
TI  - [Employed women in the Municipality of Salvador].

PMID- 14958141
TI  - [Experiences with cardiac catheterization].

PMID- 14958142
TI  - [Experience in relation to obstetric progress in the past 15 years].

PMID- 14958143
TI  - [Studies on prostatic cancer in relation to its therapy with hormones;
      determination of 17-ketosteroids and eosinophil count].

PMID- 14958144
TI  - [Cephalgia and hypertension].

PMID- 14958145
TI  - [Energetic metabolism of the central nervous system].

PMID- 14958146
TI  - [Bi-bacterial endocarditis lenta].

PMID- 14958147
TI  - [Hepatitis and cortisone].

PMID- 14958148
TI  - [Senear-Usher syndrome (pemphigus erythematosus)].

PMID- 14958149
TI  - [Suction apparatus for delivery].

PMID- 14958150
TI  - [Importance of excretion urography in urological diagnosis].

PMID- 14958151
TI  - [Bacteriological diagnosis of tuberculosis].

PMID- 14958152
TI  - [Pneumoencephalography in children].

PMID- 14958153
TI  - [Epileptic crisis as late complication of scarlet fever in menopause].

PMID- 14958154
TI  - [Problem of strabismus in children].

PMID- 14958155
TI  - [Brucellosis in children].

PMID- 14958156
TI  - [Familial hypoglycemia due to adenoma of islands of Langerhans].

PMID- 14958157
TI  - Phlebotomus and leishmaniasis.

PMID- 14958158
TI  - [Levels of salicylemia].

PMID- 14958159
TI  - [Rural medical services].

PMID- 14958160
TI  - [Thromboangiitis obliterans and arteriosclerosis obliterans; results of various
      methods of treatment based on the review of 104 cases].

PMID- 14958161
TI  - [Segmental resections in the treatment of pulmonary tuberculosis].

PMID- 14958162
TI  - [Results of oral BCG in repeated weekly doses in a case of lupus erythematosus of
      fixed type].

PMID- 14958163
TI  - [Hemochromatosis; case report].

PMID- 14958164
TI  - [Appendicitis with schistosomiasis].

PMID- 14958165
TI  - [Urological examination of uretero-vaginal fistulas].

PMID- 14958166
TI  - [Incidence of ABO blood groups in the Transfusion Service of the Sao Paulo
      Hospital das Clinicas].

PMID- 14958167
TI  - [Prof. Joaquim Motta].

PMID- 14958168
TI  - [DOCTOR Revoredo of Galen].

PMID- 14958169
TI  - [Regulations on the conferring of the specialist's degree on members of the Sao
      Paulo Medical Society].

PMID- 14958170
TI  - [Surgical therapy of bronchiectasis].

PMID- 14958171
TI  - [Coarctation of the aorta, adult type, associated with congenital bicuspid aortic
      valve; case report].

PMID- 14958172
TI  - [Schonlein-Henoch purpura treated with ACTH].

PMID- 14958173
TI  - [Streptomycin therapy of primary complex in pulmonary tuberculosis in children].

PMID- 14958174
TI  - [Neuromuscular disorders of the bladder].

PMID- 14958175
TI  - [Kidney function tests from the laboratory and clinical viewpoint].

PMID- 14958176
TI  - [Neuro-endocrine regulation of adrenal activity].

PMID- 14958177
TI  - [Electrolyte changes in renal insufficiency and its importance in the treatment
      of chronic nephritis].

PMID- 14958178
TI  - [Classification of employment and functions].

PMID- 14958179
TI  - [Blood banks].

PMID- 14958180
TI  - [Curare and curare simulants in general anesthesia].

PMID- 14958181
TI  - [General Rafael Guerrero Roldan].

PMID- 14958182
TI  - [Guide to the economic history of the national drug industry; review of its
      evolution up to the appearance of the problem of primal matter].

PMID- 14958183
TI  - [Migliano reaction in the diagnosis of syphilis].

PMID- 14958184
TI  - [Present state of cardiovascular surgery].

PMID- 14958185
TI  - [Specialized surgery in the first stage of the treatment of war wounds].

PMID- 14958186
TI  - [War wounds of the thorax; immediate treatment].

PMID- 14958187
TI  - [Value of localized rhonchus in diagnosis of bronchial stenosis].

PMID- 14958188
TI  - [Military district medical laboratory of the United States Army].

PMID- 14958189
TI  - [Medico-legal aspects of toxic effects of roentgen rays and of radioactive
      emanations].

PMID- 14958190
TI  - [Acoustic injuries in armed forces personnel].

PMID- 14958191
TI  - [Role of medical and combat officers in present problems of military medicine and
      atomic, biological and chemical warfare].

PMID- 14958192
TI  - [Technical and tactical activities of odontological officers in the regimental
      unit in combat].

PMID- 14958193
TI  - [Various considerations and experiences with Corynebacterium diphtheria ovis].

PMID- 14958194
TI  - [Osteosynthesis in management of edentulous fragments in mandibular fracture].

PMID- 14958195
TI  - Slow operative technic.

PMID- 14958196
TI  - [Indirect impressions with alginate hydrocolloids].

PMID- 14958197
TI  - [Ultrasonic therapy in dentistry].

PMID- 14958198
TI  - [Military medicine].

PMID- 14958199
TI  - [Considerations on the action of penicillin on the war wounds of the knee].

PMID- 14958200
TI  - [The physiological basis of clothing protection].

PMID- 14958201
TI  - [Military requisitions].

PMID- 14958202
TI  - [Liver function tests in current practice].

PMID- 14958203
TI  - [Antibiotic treatment of amebiasis].

PMID- 14958204
TI  - [Suture of uterus rupture during delivery].

PMID- 14958205
TI  - [Location of decidual tissue in the uterine collum].

PMID- 14958206
TI  - [Survival rate of 8 and 7 months prematures].

PMID- 14958207
TI  - [Sulfur in gynecology].

PMID- 14958208
TI  - [Laboratory method to establish hormonal balance in gynecology].

PMID- 14958209
TI  - [Spontaneous abortion in multiparae in Mussulman environment; pathogenic study].

PMID- 14958210
TI  - [Comparison of structural abnormalities of the genital glands].

PMID- 14958211
TI  - [Hypothyroidism, etiological factor in Reclus' disease].

PMID- 14958212
TI  - [Therapy of vaginal trichomoniasis with certain cationic ointments].

PMID- 14958213
TI  - [Aspects of the pathogenesis of genital tuberculosis].

PMID- 14958214
TI  - [A little known type of hemolytic anemia of the new-borne; prevention by
      isoimmunization].

PMID- 14958215
TI  - [BCG vaccination of mothers in Algiers (1925-1950)].

PMID- 14958216
TI  - [Pulmonary metastases of cancer of the cervix uteri].

PMID- 14958217
TI  - [The problem of transference; theory].

PMID- 14958218
TI  - [Introduction to the study of transference in psychoanalysis].

PMID- 14958219
TI  - [The dynamics of transference].

PMID- 14958220
TI  - [The problem of transference].

PMID- 14958221
TI  - [The origins of transference].

PMID- 14958222
TI  - [Transference].

PMID- 14958223
TI  - [Transference].

PMID- 14958224
TI  - [Transference and counter-transference in the psychoanalysis of children].

PMID- 14958225
TI  - [Transference in psychotic patients].

PMID- 14958226
TI  - [Transference].

PMID- 14958227
TI  - [Proconvertin].

PMID- 14958228
TI  - [Factor VII; its role in coagulation; its clinical importance].

PMID- 14958229
TI  - [AC globulin and SPCA: two plasma factors in the conversion of prothrombin;
      clinical and biological study and review].

PMID- 14958230
TI  - [The blood crisis in thrombosis of the coronary and pulmonary arteries;
      therapeutic deductions].

PMID- 14958231
TI  - [Antithrombin and the Lenggenhager test in the puerperium and in the period
      following normal operations or operations complicated by thrombosis].

PMID- 14958232
TI  - [Malignant disorders of the serum globulin causing hemorrhage].

PMID- 14958233
TI  - [Hemorrhagic types of myelomata].

PMID- 14958235
TI  - [Radioactivity of some springs in Trans-Jordan].

PMID- 14958234
TI  - [Cancerigenic substances].

PMID- 14958236
TI  - [Marfan's syndrome].

PMID- 14958237
TI  - [Tissue therapy in dermatology].

PMID- 14958238
TI  - [Value of routine ganglionectomy of the neck in the therapy of cancer of the
      upper respiratory and digestive tracts].

PMID- 14958239
TI  - [Report on the sanitary program (July 1950-July 1951) of the Office of relief and
      employment for the refugees from Palestine].

PMID- 14958240
TI  - [Societe Libano-Francaise de Medecine].

PMID- 14958241
TI  - [Possible correlations between tonsils, malignant lymphogranulomatosis and
      leucoses].

PMID- 14958242
TI  - [Perforated gastroduodenal ulcer and gastric aspiration].

PMID- 14958243
TI  - [Synthetic antihistaminic therapy of functional dysmenorrhea].

PMID- 14958244
TI  - [Practical results of the examination of 111 vectorcardiograms].

PMID- 14958245
TI  - [Insulin coma in therapy of schizophrenia].

PMID- 14958246
TI  - [A case of laryngeal tuberculosis with out pulmonary lesions].

PMID- 14958247
TI  - [An influenza epidemic in Lebanon].

PMID- 14958248
TI  - [A case of tetany after thyroidectomy].

PMID- 14958249
TI  - [Urinary elimination of neutral 17-ketosteroids; clinical applications].

PMID- 14958250
TI  - In memoriam Dr. Charles Martin Du Pan.

PMID- 14958251
TI  - [Surgical treatment of inguinal hernia in infant and child].

PMID- 14958252
TI  - [Hypertrophic stenosis of the pylorus (45 operated cases)].

PMID- 14958253
TI  - [Bladder extrophia and congenital absence of vagina; surgical treatment].

PMID- 14958254
TI  - [Distal methaphyseal fracture of the forearm in child].

PMID- 14958255
TI  - [Treatment of club foot by the method of J. H. Kite].

PMID- 14958256
TI  - [Treatment of infantile gastro-enteritis with synthetic antihistamines].

PMID- 14958257
TI  - [Anemia caused by goats milk].

PMID- 14958258
TI  - [Evolutions of techniques in physiotherapy; ultrasonics].

PMID- 14958259
TI  - [Bilirubin formation in blood].

PMID- 14958260
TI  - [Liver insufficiency in childhood].

PMID- 14958261
TI  - [Implantation of teeth in acrylic].

PMID- 14958262
TI  - [Oral manifestations of diabetes mellitus in juveniles].

PMID- 14958263
TI  - [Bleeding after tooth extraction].

PMID- 14958264
TI  - [Visual dental education].

PMID- 14958265
TI  - [Local thermal treatment of periodontal disease at the Marlioz Spring in Aix-les
      Bains].

PMID- 14958266
TI  - [Therapeutic desensitization and reactivation of the periodontium by filiform
      shower of mineral water].

PMID- 14958267
TI  - [Histological studies of gingivitis after treatment with salted water].

PMID- 14958268
TI  - [Ionophoresis therapy of periodontal diseases].

PMID- 14958269
TI  - [Simple means for retention of expansion plates].

PMID- 14958270
TI  - [Madrid classification and nomenclature].

PMID- 14958271
TI  - [A new method to make immediate dental prosthesis in acrylics].

PMID- 14958273
TI  - [Official bulletin of the Dental Society of France].

PMID- 14958272
TI  - [Dental inclusion in acrylic resins].

PMID- 14958274
TI  - [Lucien Cornil 1888-1952].

PMID- 14958275
TI  - [Root canal infection and therapy with antibiotics].

PMID- 14958276
TI  - [Fixation of obturators and other surgical prosthesis].

PMID- 14958277
TI  - [Waropa method for painless cavity preparation].

PMID- 14958278
TI  - [Integral syndesmotomy].

PMID- 14958279
TI  - [BULLETIN Official Company dentistry France].

PMID- 14958280
TI  - [The main role of alcoholic detoxification in the treatment of chronic
      alcoholism].

PMID- 14958281
TI  - [Water and diseases; their evolution; cancer, tuberculosis and all diseases come
      from water].

PMID- 14958282
TI  - [The effect of champagne on arterial tension and blood coagulation].

PMID- 14958283
TI  - [The alcoholic content of wines].

PMID- 14958284
TI  - [Coagulating factors].

PMID- 14958285
TI  - [Anticoagulants].

PMID- 14958286
TI  - [Sweet clover disease].

PMID- 14958287
TI  - [The simultaneous presence of alpha and beta staphylococcic antitoxins of natural
      origin in the serum of cattle].

PMID- 14958288
TI  - [The VIth International Congress of Comparative Pathology].

PMID- 14958289
TI  - [Humoral disorders observed in chronic alcoholism].

PMID- 14958290
TI  - [Has poliomyelitis become a "disease of civilization"?].

PMID- 14958291
TI  - [Vitamins E and K in the treatment of cancer of the tomato].

PMID- 14958292
TI  - [The effect of plant extracts on the in vitro activity of certain antibiotics. I.
      Essence of purified cajuput].

PMID- 14958293
TI  - [The effect of plant extracts on the in vitro motility of the duodenum of some
      mammals].

PMID- 14958294
TI  - [The use of antibiotics in veterinary medicine especially in the treatment of
      infectious diseases].

PMID- 14958295
TI  - [The role of trauma in the mummified cancer of the Malherbe type].

PMID- 14958296
TI  - [Bovine brucellosis; its discovery through milk particularly by the ring test].

PMID- 14958297
TI  - [Study of connective tissue in rheumatism; reactions of tissue permeability].

PMID- 14958298
TI  - [Osteophytes and so-called vertebral syndesmophytes].

PMID- 14958299
TI  - [Relation between the Thorn metabolic and eosinophilic test and the clinical
      results induced by ACTH].

PMID- 14958300
TI  - [Anatomical substratum of periarthritis of the shoulder].

PMID- 14958301
TI  - [Trial of a new anti-inflammatory substance in acute articular rheumatism and
      chronic progressive polyarthritis].

PMID- 14958302
TI  - [Professional degenerative rheumatism in a violinist; presentation of the
      patients and the radiographs].

PMID- 14958303
TI  - [Contribution to the study of tuberculous rheumatism; antecedents of rheumatism
      in subjects with surgical tuberculosis].

PMID- 14958304
TI  - [Thibierge-Weissenbach syndrome and generalized calcinosis].

PMID- 14958305
TI  - [Determination of urinary 11- and 17 steroids in chronic progressive
      polyarthritis].

PMID- 14958306
TI  - [Topography of Heberden's nodes in twenty-three cases of hemiplegia].

PMID- 14958307
TI  - [Case of difficult radiographic diagnosis between cancerous metastases of
      prostatic origin and cardiac lung].

PMID- 14958308
TI  - [Skeletal carcinosis of prostatic origin with osseous condensation; pathogenic
      discussion].

PMID- 14958309
TI  - [Pathological anatomy of ankylosing spondylarthritis].

PMID- 14958310
TI  - [Peripheral monarthritis and rheumatic spondylitis; danger of surgery; integrity
      of the sacroiliac].

PMID- 14958311
TI  - [Primary rheumatic lesions, reaction of connective tissue].

PMID- 14958312
TI  - [General adaptation syndrome].

PMID- 14958313
TI  - [Some aspects of the physiopathology of joints].

PMID- 14958314
TI  - [Discography].

PMID- 14958315
TI  - [One year experience with cortisone and ACTH therapy].

PMID- 14958316
TI  - [Syphilitic osteo-periostitis; radiological development in recent years].

PMID- 14958317
TI  - [Therapy of rheumatic fever and rheumatic arthritis with sodium pyrocatechol
      carboxylate].

PMID- 14958318
TI  - [Seven cases of luxation of the cervical spine].

PMID- 14958319
TI  - [French league against rheumatism; meeting of 9 January 1952].

PMID- 14958320
TI  - [Symmetrical and isolated arthritis of metacarpo-phalangial joints of the
      thumbs].

PMID- 14958321
TI  - [A case of tetany after ACTH].

PMID- 14958322
TI  - [Multiple calcification of the intervertebral disks].

PMID- 14958323
TI  - [A case of osteopetrosis Albers-Schonberg in an eight year old child].

PMID- 14958324
TI  - [Inflammatory nodes of the sacro-iliac region].

PMID- 14958325
TI  - [A case of basal arthritis of the thumb, an occupational disease].

PMID- 14958326
TI  - [Radio-tomography of the impression fractures of the cranial basis].

PMID- 14958327
TI  - [Ankylosing spondylitis].

PMID- 14958328
TI  - [Rheumatism, a social scourge].

PMID- 14958329
TI  - [Bornholm disease].

PMID- 14958330
TI  - [The value of lymphocytes in rheumatoid arthritis].

PMID- 14958331
TI  - [Adrenocortical steroids and inflammation; experimental study].

PMID- 14958332
TI  - [Thoracic and precordial pain in the course of cervical arthrosis].

PMID- 14958333
TI  - [Attempts to demonstrate an anti-inflammatory substance in the blood of patients
      treated with cortisone].

PMID- 14958334
TI  - [Tenosynovitis of the long biceps tendum; a type of periarthritis humero-scapular
      too little known].

PMID- 14958335
TI  - [Ultrasonics and Spa therapy of rheumatic diseases].

PMID- 14958336
TI  - [French league against rheumatism; meeting of 12 February 1952].

PMID- 14958337
TI  - [Two cases of pulmonary tuberculosis after treatment with ACTH and cortisone;
      considerations on the risk of tuberculosis in therapy with adreno-cortical
      hormones].

PMID- 14958338
TI  - [A case of arthrogryposis multiplex congenita observed up to the age of 23
      years].

PMID- 14958339
TI  - [Muscles in chronic evolutive polyarthritis].

PMID- 14958340
TI  - [Kahler's disease improved by cortisone].

PMID- 14958341
TI  - [Cortisone therapy of sciatica caused by disk diseases].

PMID- 14958342
TI  - [Pseudo-coxarthritis with Brailsford-Morquio's syndrome].

PMID- 14958343
TI  - [Gougerot-Sjogren syndrome; local effect of cortisone on eye lesions].

PMID- 14958344
TI  - [Attempts to apply ACTH by way of mucous membranes].

PMID- 14958345
TI  - [Nervous arthropathy for no detectable nervous reason].

PMID- 14958346
TI  - [Remarks on knee lesions in chronic evolutive polyarthritis derived from clinical
      observations of 20 patients in the hospital Reine-Hortense of Aix-Les-Bains].

PMID- 14958347
TI  - [Postero-anterior radiography of the lumbar spine giving good results].

PMID- 14958348
TI  - [Anatomo-histological study of the lumbar vertebral bodies].

PMID- 14958349
TI  - [Intra-articular effect of hydrocortisone].

PMID- 14958350
TI  - [XXV anniversary of the Belgian League against the rhumarisme Brussels, 10
      November 1951].

PMID- 14958351
TI  - [Symmetrical bilateral defect of the diaphragm with monolateral hernia;
      pathogenesis and classification].

PMID- 14958352
TI  - [Primary sarcoma of the liver].

PMID- 14958353
TI  - [Histochemistry of eosinophilic granulocytes in a case of eosinophilic granuloma
      in bone].

PMID- 14958354
TI  - [Contribution to the study of lipomas of the uterus].

PMID- 14958355
TI  - [Very unusual localization of adenolymphoma].

PMID- 14958356
TI  - [Oncocytes in various pathological affections of the larynx].

PMID- 14958357
TI  - [Alterations of the thymus and other endocrine glands after irradiation of the
      pituitary in thymo-pituitary correlation; critical review, with experimental
      contribution].

PMID- 14958358
TI  - [Vitamin A alone and associated with streptomycin in the treatment of
      experimental miliary pulmonary tuberculosis in rabbits].

PMID- 14958359
TI  - [Study of a case of juvenile delinquency with aggressive neurotic behavior; its
      multifactoral structure].

PMID- 14958360
TI  - [Blood, cerebrospinal and urinary levels of 4-4'-diaminodiphenylsulphone in ethyl
      oleate suspension in tuberculous meningitis].

PMID- 14958361
TI  - [Lipoid nephrosis and its treatment with ACTH].

PMID- 14958362
TI  - [Study of cranial proportions in the newborn by means of lateral
      cranioradiograms].

PMID- 14958363
TI  - [Associated therapy in experimental streptomycin-resistant tuberculosis].

PMID- 14958364
TI  - [Absorption of vitamin A by rectal administration].

PMID- 14958365
TI  - [Alterations of the thymus and other endocrine glands after irradiation of the
      pituitary in thymo-pituitary correction; critical review with experimental
      contribution].

PMID- 14958366
TI  - [Hormone picture in Turner syndrome].

PMID- 14958367
TI  - [Arteriovenous anastomoses and intravascular formation of obstruction in the
      uterus in late pregnancy].

PMID- 14958368
TI  - [Case of velamentous insertion of the umbilical cord with fetal death during the
      explusive period].

PMID- 14958369
TI  - [Hypotensive therapy of eclamptic syndromes].

PMID- 14958370
TI  - [Hyaluronidase and milk secretion].

PMID- 14958371
TI  - [State of Hormones in uterine hypoplasia].

PMID- 14958372
TI  - [Cardiac and bronchial asthma].

PMID- 14958373
TI  - [Notes on tyrothricin].

PMID- 14958374
TI  - [Weekly epidemiological report; week of 6-12 January 1952].

PMID- 14958376
TI  - [Hypophysial obesity in children].

PMID- 14958375
TI  - [Dr. G. Derscheid 1871-1952].

PMID- 14958377
TI  - [The early diagnosis of cancer of the cervix uteri].

PMID- 14958378
TI  - [Weekly epidemiological report; week of 20-26 January, 1952].

PMID- 14958379
TI  - [The incubation and its dissociated phases in pulmonary tuberculosis].

PMID- 14958380
TI  - [Resistance of the tubercle-bacillus to drugs in general and PAS in particular].

PMID- 14958381
TI  - [Effect of pyazoles, especially irgapyrin on the PAS blood level; retard action].

PMID- 14958383
TI  - [A review of the 1950 German literature on tuberculosis].

PMID- 14958382
TI  - [Effect of vitamin D2 on experimental tuberculosis in rats; morphological and
      histochemical studies (acid and alkaline phosphatase)].

PMID- 14958384
TI  - [A new method of tomography].

PMID- 14958385
TI  - [Unusual widening of the trachea caused by tuberculosis].

PMID- 14958386
TI  - [Extrapleural pneumolysis in children].

PMID- 14958387
TI  - [Prognosis of active pulmonary tuberculosis in children and adolescents].

PMID- 14958388
TI  - [Additional pathological examinations on meningitis tuberculosis treated with
      streptomycin and paraaminosalicylic acid].

PMID- 14958390
TI  - [Not Available].

PMID- 14958389
TI  - [Scandinavian tuberculosis literature 1949-50].

PMID- 14958391
TI  - [Vaccination reactions and tuberculous diseases after BCG inoculation].

PMID- 14958392
TI  - [Functional x-ray diagnosis with a new universal x-ray mass survey apparatus].

PMID- 14958393
TI  - [Experimental experiences with the antituberculous compound rimifon].

PMID- 14958394
TI  - [First observations of patients treated with a new chemotherapeutic agent].

PMID- 14958395
TI  - [Rimifon in the therapy of tuberculosis; first clinical observations].

PMID- 14958396
TI  - [Comparison of early therapeutic results of pulmonary tuberculosis with rimifon].

PMID- 14958397
TI  - [Preliminary experiences with rimifon in cutaneous and genital tuberculosis].

PMID- 14958398
TI  - [Clinical and laboratory experiences with isonicotinic acid hydrazide].

PMID- 14958399
TI  - [Retardation of elimination of paraminosalicylic acid by benemid].

PMID- 14958400
TI  - [Effects of benemid on the PAS blood level; its therapeutic use in tuberculosis].

PMID- 14958401
TI  - [Irgapyrin causing retardation].

PMID- 14958402
TI  - [Extraarticular foci of long bones].

PMID- 14958403
TI  - [Some diagnostic and therapeutic difficulties in sacroiliac tuberculosis].

PMID- 14958404
TI  - [Implantation of fresh homografts in osteoarticular tuberculosis].

PMID- 14958405
TI  - [Tuberculos mastoiditis in a 14 months old infant].

PMID- 14958406
TI  - A study on the water content in the dried BCG vaccine.

PMID- 14958407
TI  - Behavior of leprosy bacilli implanted in various liquid media by means of slide
      culture method.

PMID- 14958408
TI  - Metabolism of tubercle bacilli; metabolism of carbohydrate and inorganic
      substances of tubercle bacilli.

PMID- 14958409
TI  - The influence of tissue fixatives and other various fluids upon the staining of
      acid-fast bacilli.

PMID- 14958410
TI  - Detection and acid-fast forms of tubercle bacilli in sputum in relation to
      varying staining conditions in Ziehl-Neelsen stain.

PMID- 14958411
TI  - Comparison of cultivations of tubercle bacilli from tracheal lavage liquid and
      gastric juice.

PMID- 14958412
TI  - Comparison of immunities against tuberculosis between the guinea pigs treated
      with dead tubercle bacilli paraffin-oil vaccine and those treated with BCG, by
      the method of slide cell culture.

PMID- 14958413
TI  - Distribution of streptomycin in various organs and fluids following intramuscular
      injection.

PMID- 14958414
TI  - A study of the pulmonary tuberculous patients complicated with intestinal
      tuberculosis, particularly on the blood and the indican-quantity in the urine;
      III. A comparison of the indican-quantities on the urine between two groups, the
      pulmonary tuberculous patients complicated with and without intestinal
      tuberculosis.

PMID- 14958415
TI  - [Reasons for the increased use of cytological methods].

PMID- 14958416
TI  - [Technics for cytologic specimen taking and preparation].

PMID- 14958417
TI  - [Indications for cytological technics].

PMID- 14958418
TI  - [A study of results gained from cytologic technics and principal causes for
      errors].

PMID- 14958419
TI  - [ACTH and Cortisone in rheumatology].

PMID- 14958420
TI  - [Ground substance of the mesenchyme and spreading factors in infection].

PMID- 14958421
TI  - [Certain hydrogenated ergot alkaloids in the therapy of hypertensive disease].

PMID- 14958422
TI  - [The periodic disease].

PMID- 14958423
TI  - [Effects of cortisone in alcoholic liver cirrhosis; clinical, biological and
      histological aspects].

PMID- 14958424
TI  - [Biochemical diagnosis of renal lithiasis].

PMID- 14958425
TI  - [Blood changes observed in patients affected by chronic evolutive polyarthritis
      treated with ACTH or cortisone].

PMID- 14958426
TI  - [Comparative effects of a single injection of corticotropic hormone or cortisone
      on the blood cells and bone marrow of man].

PMID- 14958427
TI  - [Radiologic signs of brachyesophagus & diaphragmatic hernia in the infant].

PMID- 14958428
TI  - [The present medical and surgical treatment of permanent arterial hypertension].

PMID- 14958429
TI  - [Sodium salicylate, aspirin and corticosteroids in therapy of Bouillaud's
      disease].

PMID- 14958430
TI  - [Cardio-angiographic and hemodynamic diagnosis of pure pulmonary stenosis].

PMID- 14958431
TI  - [Research on the pathogenesis of cardiac disorders in hyperfolliculinism].

PMID- 14958432
TI  - [Pathologic arterio-venous inter-relationships of the extremities; present
      concepts].

PMID- 14958433
TI  - [The path of the aorta and the esophagus].

PMID- 14958434
TI  - [Case of isolated congenital pulmonary artery stenosis].

PMID- 14958435
TI  - [Commissurotomy and mitral stenosis].

PMID- 14958436
TI  - [Probable mechanism of cortisone action].

PMID- 14958437
TI  - [Pre-menstrual tension; vitamin A therapy].

PMID- 14958438
TI  - [Endolaryngeal paracoccidioidic granuloma].

PMID- 14958439
TI  - [A new form of neurological disorder caused by carbon monoxide poisoning].

PMID- 14958440
TI  - [Trial therapy of bronchitis in the aged].

PMID- 14958441
TI  - [Seminar on pathology, clinical medicine and surgical technique: glioma in
      central nuclei in the thalamo-hypothalamic region].

PMID- 14958442
TI  - [Seminar on pathology, clinical medicine and surgical technique: coronary suture
      meningioma].

PMID- 14958443
TI  - [ACTH therapy of nephrosis].

PMID- 14958444
TI  - [Therapy of non-extirpable cystic gliomas with mural nodule].

PMID- 14958445
TI  - [Senile dementia; retrospective diagnosis of insanity].

PMID- 14958446
TI  - [Grave dystocia after ligamentopexia].

PMID- 14958447
TI  - [Neosalvarsan, atropine sulfate and trypaflavin in subcutaneously injected rats:
      absence of cancerigenic effect of the first two and induced sarcoma in the site
      of trypaflavin injection].

PMID- 14958448
TI  - [Comparative study of three antacids of prolonged effect].

PMID- 14958449
TI  - [Seminar on pathology, clinical medicine and surgical technique: adenomatous
      polyps of the colon].

PMID- 14958450
TI  - [Iridencleisis (Holth's operation)].

PMID- 14958451
TI  - [A new synthetic antituberculosis drug: isonicotinic acid hydrazide].

PMID- 14958452
TI  - [Convulsions in children].

PMID- 14958453
TI  - [Use of antioxygens in therapy of collagen diseases].

PMID- 14958454
TI  - [Concept of integration in health service plans and construction].

PMID- 14958455
TI  - [Rickets in the practice of the outpatient department. Part II].

PMID- 14958456
TI  - [Seminar on pathology, clinical medicine and surgical technique; sigmoid
      adenocarcinoma with metastasis to liver].

PMID- 14958457
TI  - [Pregnancy and delivery in the obese].

PMID- 14958458
TI  - [Accuracy of statistical data in pulmonary tuberculosis].

PMID- 14958459
TI  - [Diverticulosis of the colon in children].

PMID- 14958460
TI  - [Orthopedics in some European countries].

PMID- 14958461
TI  - [Treatment of the common cold and rhinitis with oral vaccine].

PMID- 14958462
TI  - [Primary cholangioma of the liver with pulmonary metastasis].

PMID- 14958463
TI  - [Idleness and hysteria].

PMID- 14958464
TI  - [Seminar on pathology. clinical medicine and surgical technique: retroperitoneal
      lymphosarcoma].

PMID- 14958466
TI  - [Life insurance physicians convene in Stockholm].

PMID- 14958465
TI  - [Seminar on pathology, clinical medicine and surgical technique: pleural
      empyema].

PMID- 14958467
TI  - [Health and medical care in Great Britain; observations and impressions from a
      visit to England and Scotland].

PMID- 14958469
TI  - [Quackery in Sweden; comments and date with reference to current discussion].

PMID- 14958468
TI  - [Psychopathological conditions in pupils in schools for retarded children].

PMID- 14958470
TI  - [Politics involve WHO, but the practical work goes on].

PMID- 14958471
TI  - [Mortality in the Swedish counties and the genetic effect of isolated
      communities].

PMID- 14958472
TI  - [Value of tests for maturity of children at school age].

PMID- 14958473
TI  - Serum iron in the Tswana (Bechuanaland).

PMID- 14958474
TI  - Lethal action of abdominal irradiation in the rat.

PMID- 14958475
TI  - The toxicity of Ochna pulchra Hook, fil.

PMID- 14958476
TI  - Haemophilia in a South African Bantu child.

PMID- 14958477
TI  - Sequence in the time of ossification of the carpal bones in 705 African children
      from birth to six years of age.

PMID- 14958478
TI  - Gastric secretion of potassium.

PMID- 14958479
TI  - The electrocardiographic and plasma potassium changes after adrenalin and insulin
      injections.

PMID- 14958480
TI  - An examination of biophysical methods for determining changes in body
      temperature.

PMID- 14958481
TI  - Changes in cardiac output with progressive work.

PMID- 14958482
TI  - Some observations on the gastro-oesophageal sphincteric mechanism.

PMID- 14958483
TI  - Lay foundations and federal bureaus with medical significance and with special
      reference to cardiovascular disease.

PMID- 14958484
TI  - Industrial medicine at a TVA construction project.

PMID- 14958485
TI  - Surgery.

PMID- 14958486
TI  - Pediatrics.

PMID- 14958487
TI  - Re-emphasis of some old truths in neurology and neurosurgery.

PMID- 14958488
TI  - Surgery.

PMID- 14958489
TI  - Eye-accident management by the family doctor.

PMID- 14958490
TI  - Cardiac auscultation of great diagnostic value.

PMID- 14958491
TI  - Personality changes in armless veterans.

PMID- 14958492
TI  - Diagnosis and treatment of tachycardias outside hospitals.

PMID- 14958493
TI  - Pudendal nerve block in private obstetric practice.

PMID- 14958494
TI  - DR. Lester Avant Crowell.

PMID- 14958495
TI  - NOTED heart specialist to speak at Southwestern meeting.

PMID- 14958496
TI  - The care of crossed eyes.

PMID- 14958497
TI  - Cystic malignant melanoma of the ciliary body.

PMID- 14958498
TI  - Interpulmonary circumscribed lesions.

PMID- 14958499
TI  - [Vaccinating activity of extracts of typhoid bacteria].

PMID- 14958500
TI  - [Noxiceptivity of the anterior wall of the peritoneum; experimental research].

PMID- 14958501
TI  - [Contribution to the study of pancreatic fibrinolytic enzymes].

PMID- 14958502
TI  - [Conjugation of glycuronic acid with o-aminophenol in rat organ slices].

PMID- 14958503
TI  - [Receptivity of the normal guinea pig to endovenous typhoid infection].

PMID- 14958504
TI  - Orcein and elastic fibers.

PMID- 14958505
TI  - Staining and mounting helminths.

PMID- 14958506
TI  - Mapping goblet cells in mucous membranes.

PMID- 14958507
TI  - A modified turchini technic for the differential staining of nucleic acids.

PMID- 14958508
TI  - Studies on the preparation and recoloration of fuchsin sulfurous acid.

PMID- 14958509
TI  - Effectiveness of schiff variants in the periodic-schiff and feulgen nucleal
      technics.

PMID- 14958510
TI  - Selective silver impregnation of degenerating axons in the central nervous
      system.

PMID- 14958511
TI  - Mucosal whole mounts of rodent forestomach.

PMID- 14958512
TI  - The effect of temperature and of relative humidity on sectioning of tissues
      embedded in polyethylene glycol wax.

PMID- 14958513
TI  - Aceto-carmine-lactophenol preparations of paramecium aurelia.

PMID- 14958514
TI  - Mounting macerated plant tissues with adhesives.

PMID- 14958515
TI  - A rapid method for concentrating small organisms for sectioning.

PMID- 14958516
TI  - Permanent mounts of chromosomes after 8-oxyquinoline and squashing.

PMID- 14958517
TI  - Handling avian chromosomes.

PMID- 14958518
TI  - Formalin-pyrogallol as a fixative for plant cytoplasm.

PMID- 14958519
TI  - Staining the fibrin network in blood smears.

PMID- 14958520
TI  - The use of phodizonate in enzymatic histochemistry.

PMID- 14958521
TI  - Combined use of antibiotics.

PMID- 14958522
TI  - William Stewart Halsted as revealed in his letters.

PMID- 14958523
TI  - The public health aspects of latent syphilis.

PMID- 14958524
TI  - Cat scratch fever.

PMID- 14958525
TI  - An anatomic study of a case of cystinosis.

PMID- 14958526
TI  - Phase microscopic study of fixed stained specimens.

PMID- 14958527
TI  - The effect of various anterior pituitary fractions on the amino acid
      concentration of the blood.

PMID- 14958528
TI  - Trysin in an ointment base; a preliminary report.

PMID- 14958529
TI  - The treatment of selected dermatoses with crystalline trypsin ointment.

PMID- 14958530
TI  - The prevention of breast engorgement.

PMID- 14958531
TI  - The treatment of gastrojejunal ulceration.

PMID- 14958532
TI  - Berylliosis; case report.

PMID- 14958533
TI  - Technical improvements in intestinal anastomoses.

PMID- 14958534
TI  - [Experimental investigations on hyperthermia therapy of neoplasms].

PMID- 14958535
TI  - [Experiences and results of x-ray therapy of bronchiogenic and pulmonary
      neoplasms].

PMID- 14958536
TI  - [A new dosiometer with a flexible crystal probe; its clinical use].

PMID- 14958537
TI  - [Effects of x-rays on prothrombin level of the human blood].

PMID- 14958538
TI  - [Advantage of inflammation dosage of irradiation in combination with
      chemotherapy].

PMID- 14958539
TI  - [Therapy of the breast cancer].

PMID- 14958540
TI  - [Experiences with radium therapy of cavernous hemangiomata].

PMID- 14958541
TI  - [Combined therapy of bronchogenic carcinoma with x-rays and ultrasonics].

PMID- 14958542
TI  - [Crystal scintillation counter, a new method of dosiometry].

PMID- 14958543
TI  - [Radiotherapy and prognosis of lymphogranulomatosis].

PMID- 14958544
TI  - [Roentgenological observations in macrofollicular lymphoblastoma (Brill-Symmer's
      disease)].

PMID- 14958545
TI  - [The mitotic rhythm of carcinomas of the human skin; effects of Chaoul's
      irradiation on it].

PMID- 14958546
TI  - [Histochemical and serological investigations on the effects of x rays. II.
      Acetalphosphatides, in spleen, in the thymus gland, the small intestines and the
      myocardium of the rat after a whole body irradiation with 1000 r].

PMID- 14958547
TI  - [Physical explanation of the effects of different time factors on biological
      objects].

PMID- 14958548
TI  - [10 Years preoperative irradiation of the breast cancer].

PMID- 14958549
TI  - [The problem of reaction in biological radiation effects].

PMID- 14958550
TI  - [Modern procedures in cancer diagnosis].

PMID- 14958551
TI  - [Surgery in mitral stenosis; a case of commissurotomy].

PMID- 14958552
TI  - [Neurological manifestations during myocardial infarct].

PMID- 14958553
TI  - [Anesthesia potentialization and hibernation in thoracic surgery].

PMID- 14958554
TI  - [Segmentary resection for tuberculosis].

PMID- 14958555
TI  - [Four cases of cardiac arrest in thoracic surgery, three of the cases followed by
      resuscitation].

PMID- 14958556
TI  - [Neuro-surgical aspect of current epilepsy therapy].

PMID- 14958557
TI  - [Streptomycin resistance of tubercle bacilli. IV. Effect of the idea of
      resistance on the conduct of streptomycin therapy of human tuberculosis].

PMID- 14958558
TI  - [Rapid technique of differential cytological staining for detection of exfoliated
      neoplastic cells in biological fluids].

PMID- 14958559
TI  - [Syphilis seroreactions and their interpretation].

PMID- 14958560
TI  - [Dermatological dressing].

PMID- 14958561
TI  - [Anatomicopathological data on pulmonary cancer].

PMID- 14958562
TI  - [Pulmonary cancers found at autopsy and not suspected clinically].

PMID- 14958563
TI  - [Pulmonary cancer and tuberculosis].

PMID- 14958564
TI  - [Pulmonary cancer and pulmonary silicosis].

PMID- 14958565
TI  - [Histopathological diagnosis of pulmonary cancer by examination of expectorated
      casts].

PMID- 14958566
TI  - [Histopathological diagnosis of pulmonary cancer by microscopic examination of
      sections of fixed sputum; value of results and limitations of the method].

PMID- 14958567
TI  - [Histological diagnosis of bronchial cancer by biopsy and endobronchial
      aspiration; 434 examinations].

PMID- 14958568
TI  - [Diagnosis of bronchial cancer; 200 cases histologically confirmed by
      endobronchial specimens].

PMID- 14958569
TI  - [Early cytological diagnosis of bronchopulmonary cancer; aspiration directed by a
      new device; cytological aspects].

PMID- 14958570
TI  - [Results of cytological examinations in the diagnosis of lung tumors].

PMID- 14958571
TI  - [Difficulties in diagnosis of bronchial cancer].

PMID- 14958572
TI  - [Transverso-axial tomography in pulmonary and bronchial cancer].

PMID- 14958573
TI  - [Statistics on primary cancers of the lung observed at the Medical Clinic A from
      1949 to 1951].

PMID- 14958574
TI  - [Thirty-two cases of bronchial cancer].

PMID- 14958575
TI  - [Cutaneous generalization in the evolution of hilar bronchial epithelioma with
      dark cells].

PMID- 14958576
TI  - [Method of mediastinal ganglionectomy after pneumonectomy for cancer].

PMID- 14958577
TI  - [Exeresis of bronchial cancers following radiotherapy].

PMID- 14958578
TI  - [Effect of radiotherapy on surgical conditions in bronchial cancer and on the
      immediate results of surgery].

PMID- 14958579
TI  - [Indication for and management of pre-operative irradiation].

PMID- 14958580
TI  - [Anatomical and histological findings on irradiated cancers of the lungs; autopsy
      findings].

PMID- 14958581
TI  - [Examination of surgical specimens of irradiated bronchial cancers].

PMID- 14958582
TI  - [Radiotherapy in bronchial cancer].

PMID- 14958583
TI  - [Radiotherapy in bronchial cancer, or so-called pulmonary cancer].

PMID- 14958584
TI  - [Pneumoperitoneal aspiration].

PMID- 14958585
TI  - [Indications for surgery in phlebitis sequellae].

PMID- 14958586
TI  - [The importance and possibility of early diagnosis in tuberculous meningitis].

PMID- 14958587
TI  - [Six new cases of tuberculous meningitis cured by streptomycin therapy].

PMID- 14958588
TI  - [Tuberculous meningitis and pregnancy; favorable therapeutic results in two
      cases].

PMID- 14958589
TI  - [Inoperable epithelioma of the right jaw bone; radiotherapy; recovery after four
      and-a half years].

PMID- 14958590
TI  - [Surgical treatment of bilateral paralysis of the abductors of the larynx; three
      cases of cordopexy cured by surgery].

PMID- 14958591
TI  - [Elementary reactions and lesions of the adrenal cortex].

PMID- 14958592
TI  - [Pharmacy in present day Germany].

PMID- 14958593
TI  - [New additions to the Swedish pharmacopeia].

PMID- 14958595
TI  - [Two gratifying events].

PMID- 14958594
TI  - [Comments on the pharmacopeial revision].

PMID- 14958597
TI  - [Reforms proposed by the pharmaceutical profession].

PMID- 14958596
TI  - Preparation and determination of diethyl p-nitrophenyl phospate (E 600) a drug
      used in the treatment of glaucoma.

PMID- 14958598
TI  - [Reforms proposed by the pharmaceutical profession. II].

PMID- 14958599
TI  - [A nearly ideal pharmacy].

PMID- 14958600
TI  - [NFN names; names approved by the Scandinavian pharmacopeial committee].

PMID- 14958601
TI  - [Determination of arbutin in bearberry leaves under various conditions].

PMID- 14958602
TI  - [Studies on occlusal changes in the adult dentition].

PMID- 14958603
TI  - [Temporary stenosis and dilatation of the sublingual duct].

PMID- 14958604
TI  - [Magnetic prostheses].

PMID- 14958605
TI  - [Anchorage of the core of crowns and gold inlays].

PMID- 14958606
TI  - [Comparative tests of retention of cemented cylindrical cores].

PMID- 14958607
TI  - [Comment on P. Goransson's article, Exposure of the gingival margin in indirect
      hydrocolloid impression technique].

PMID- 14958608
TI  - [Reply to S. Karlstrom's comment on my article, Exposure of the gingival margin
      in indirect hydrocolloid impression technique].

PMID- 14958609
TI  - [Practical considerations on diagnosis, therapy and control of venereal
      diseases].

PMID- 14958610
TI  - [Clinical results with linoral (ethinylestradiol)].

PMID- 14958611
TI  - [High quinidine dosage].

PMID- 14958612
TI  - [Abuse of iodine and thiouracil].

PMID- 14958614
TI  - [Metabolic tests with Jones' apparatus].

PMID- 14958613
TI  - [Encephalopathy due to carbon monoxide poisoning; reply to Professor Kinberg].

PMID- 14958615
TI  - [Experiences of a physician in Egypt].

PMID- 14958616
TI  - [Law on revision of the statutes on communicable diseases comments of the
      Lakarforbund on the proposals of the medical directorate].

PMID- 14958617
TI  - [Diabetes; granting of certain benefits to diabetics].

PMID- 14958618
TI  - [The physicians and injury testimony in accidents].

PMID- 14958619
TI  - [Tuberculosis, a conquered widespread disease].

PMID- 14958620
TI  - [A case of acute leukosis caused by benzol poisoning].

PMID- 14958621
TI  - [Husbands of women seeking abortion].

PMID- 14958622
TI  - [Cancer mortality, past and present].

PMID- 14958623
TI  - [Prevention and therapy of contractures, deviations and deformations in
      rheumatoid arthritis].

PMID- 14958624
TI  - [Further results in biopsy of the gastric mucosa with non-optical instruments and
      reconstructed bioptical instruments adaptable to the flexible gastroscope].

PMID- 14958625
TI  - [Review of hearing tests of 26,000 school children in Stockholm].

PMID- 14958626
TI  - [Social-psychiatric considerations on the gypsies in Sweden].

PMID- 14958627
TI  - [Eventual need of treatment of alcoholism both in a psychiatric hospital and in
      an institution for alcoholists].

PMID- 14958628
TI  - [On psychogenesis, etc].

PMID- 14958629
TI  - [Geriatric research].

PMID- 14958630
TI  - [Analysis of ricket cases during 4 years].

PMID- 14958631
TI  - [Comparison between clinical and x-ray diagnosis of rickets].

PMID- 14958632
TI  - [Intravenous PAS therapy].

PMID- 14958633
TI  - [Qualifications of general hospital physicians].

PMID- 14958634
TI  - [Tentative use of climatotherapy in the Canary Islands].

PMID- 14958635
TI  - [Special training of nurses; opinions of the Lakarforbund on the draft by the
      Committee].

PMID- 14958636
TI  - [Sharpened tuberculosis control of school teachers].

PMID- 14958637
TI  - [The riddle of neoplastic diseases; how to solve the problem].

PMID- 14958638
TI  - [The 1951 poliomyelitis epidemic; report from the bureau of medical care,
      Medicinalstyrelsen].

PMID- 14958639
TI  - [Treatment of acute cardiac arrest during surgery].

PMID- 14958640
TI  - [Hypopotassemic alkalosis in gastrointestinal obstruction].

PMID- 14958641
TI  - [Medical research and cancer therapy with use of ultrahard x-rays and powerful
      electrons].

PMID- 14958642
TI  - [PAS concentration in blood in therapeutic use of PAS and its salts].

PMID- 14958643
TI  - [25 Year anniversary of Sveriges praktiserande lakares forening].

PMID- 14958644
TI  - [Training of nursing personnel for mental hospitals; opinions of the
      Lakarforbund].

PMID- 14958645
TI  - [Objections to the socialization of pharmacies].

PMID- 14958646
TI  - [Maternal welfare policy in France; a precedent for Sweden].

PMID- 14958647
TI  - [Anticoagulant therapy of heart infarct].

PMID- 14958648
TI  - [Prevention, therapy and mortality of tuberculosis; reflections on Dr. Erik
      Forsgren's article].

PMID- 14958649
TI  - [Controversial budgetary considerations on staffing of the pediatric division of
      Karolinska sjukhuset].

PMID- 14958650
TI  - [Qualifications and salary classes of hospital stenographers].

PMID- 14958651
TI  - [Revision of the law on insurance for certain occupational diseases].

PMID- 14958652
TI  - [License regulations, etc., concerning foreign physicians; opinions of the
      Lakarforbund on the proposals of the medical directorate].

PMID- 14958653
TI  - [Qualifications of general hospital physicians; letter to the Kin from
      Docentforeningen vid Karolinska Institutet].

PMID- 14958654
TI  - [Vadstena, an old hospital town; chapters from the history of Vadstena hospital].

PMID- 14958655
TI  - [Vaccination against whooping cough].

PMID- 14958656
TI  - [Brief orientation regarding the latest remedies against tuberculosis].

PMID- 14958657
TI  - [Mercurochrome in prevention of urine retention following gynecological surgery].

PMID- 14958658
TI  - [The aged and hospitals].

PMID- 14958659
TI  - [The new classification adopted by Medicinalstyrelsen; a clarification].

PMID- 14958660
TI  - [Puncture of the myocardium in therapy of cardiac arrest].

PMID- 14958661
TI  - [New plan for mass health examinations].

PMID- 14958662
TI  - [Medicine and journalism].

PMID- 14958663
TI  - [The duration of immunity after Calmette vaccination].

PMID- 14958664
TI  - [Hyperthyroidism in the climacteric].

PMID- 14958666
TI  - [Pain in paralysis agitans].

PMID- 14958665
TI  - [Psychogenic hyperventilation and its clinical significance].

PMID- 14958667
TI  - [The three medical faculties in Sweden in the 19th and first half of the 20th
      century].

PMID- 14958668
TI  - [Cumbersome conditions; a causerie].

PMID- 14958669
TI  - [Not Available].

PMID- 14958670
TI  - [The debated personnel requirements of the pediatric clinic at the Karolinska
      hospital].

PMID- 14958671
TI  - [The conflict concerning abortion].

PMID- 14958672
TI  - [Studies with radioactive Calmette vaccine].

PMID- 14958673
TI  - [Rectoscopy in routing examination for early detection of rectal cancer].

PMID- 14958674
TI  - [Improved bandage for colostomized patients].

PMID- 14958675
TI  - [Comments on the reorganization of the Lakarforbund].

PMID- 14958676
TI  - [Disease in prohibition of marriage contract].

PMID- 14958677
TI  - [Decisions by the World Medical Association].

PMID- 14958678
TI  - [New contributions to the debate on abortion].

PMID- 14958679
TI  - [Intensive therapy of cardiac decompensation. II. Use of diurgin, a new mercurial
      diuretic, and brief low sodium diet].

PMID- 14958680
TI  - [Synergism and antagonism of antibiotics].

PMID- 14958681
TI  - [Use of antibiotics in otology].

PMID- 14958682
TI  - [Definition of lesion].

PMID- 14958683
TI  - [Indications and counterindications of PAS therapy].

PMID- 14958684
TI  - [Medical secretaries in hospitals].

PMID- 14958685
TI  - [The right of the physician to refuse abortion].

PMID- 14958686
TI  - [Premature infants].

PMID- 14958687
TI  - [Casein dried milk for dyspeptic infants].

PMID- 14958688
TI  - [Effectivity of the occlusive pessary].

PMID- 14958689
TI  - [Phenacetyl carbamide (phenurone) therapy of convulsive conditions].

PMID- 14958690
TI  - [The risk of air embolism in blood donation].

PMID- 14958691
TI  - [Old age care].

PMID- 14958692
TI  - [Pulmonary candidosis (moniliasis) and antibiotic therapy].

PMID- 14958693
TI  - [Thyrotoxicosis of extraneous origin].

PMID- 14958694
TI  - [Tuberculosis mortality in Sweden].

PMID- 14958695
TI  - [Mortality in surgery for pulmonary tuberculosis].

PMID- 14958696
TI  - [Increased noradrenalin secretion in thallium poisoning].

PMID- 14958697
TI  - [Psychiatric follow-up of women after legal abortion].

PMID- 14958698
TI  - [Fees for endoscopic examination; examination; medical opinion with reference to
      health insurance regulation].

PMID- 14958699
TI  - [The straight and narrow path].

PMID- 14958700
TI  - [Cancer mortality].

PMID- 14958701
TI  - [Vitamin K therapy of acute hepatitis].

PMID- 14958702
TI  - [Explosives causing headache].

PMID- 14958703
TI  - [Essential importance of the psychogenic hypothesis].

PMID- 14958704
TI  - [Research organization for hospital planning].

PMID- 14958705
TI  - [Incidence of iron deficiency among 462 cases in an extensive polyclinical
      material].

PMID- 14958706
TI  - [Caries and caries prevention].

PMID- 14958707
TI  - [Tooth decay in infancy].

PMID- 14958708
TI  - [Two cases of pregnancy rubella and congenital defects].

PMID- 14958709
TI  - [Sickness insurance, law on epidemics, midwives].

PMID- 14958710
TI  - [Official statistics on incidence of legal abortion].

PMID- 14958711
TI  - [Conservative cyst surgery; report on 4 conservatively operated dental cysts in
      children].

PMID- 14958712
TI  - [Course of infection in cervicofacial actinomycosis].

PMID- 14958713
TI  - [Intra-alveolar root fractures].

PMID- 14958714
TI  - [Unilateral mandibular hyperplasia].

PMID- 14958715
TI  - [Symptomatic trigeminal neuralgia of dental origin].

PMID- 14958716
TI  - [Surgery of cysts of the jaw with special consideration of so-called
      fenestration].

PMID- 14958717
TI  - [Oroantral (antro-alveolar) fistulas and their treatment].

PMID- 14958718
TI  - [Preliminary report on the relation between ocular and dental disease].

PMID- 14958719
TI  - [Dentist Erik Gustav Fiehn].

PMID- 14958721
TI  - [Not Available].

PMID- 14958720
TI  - [In memoriam Axel Schmidt, dentist].

PMID- 14958722
TI  - [Progress in internal medicine].

PMID- 14958723
TI  - [Recent progress in surgery].

PMID- 14958724
TI  - [Progress in endocrinology].

PMID- 14958725
TI  - [Recent progress in the treatment of blood diseases].

PMID- 14958726
TI  - [Recent progress in cardiology].

PMID- 14958727
TI  - [Progress in treatment of pulmonary tuberculosis].

PMID- 14958729
TI  - [Recent progress in neurology].

PMID- 14958728
TI  - [Progress in the treatment of skin diseases].

PMID- 14958730
TI  - [Recent progress in the treatment of virus diseases].

PMID- 14958731
TI  - [Recent progress in the treatment of allergy].

PMID- 14958732
TI  - [The role of bronchoscopy in otolaryngology].

PMID- 14958733
TI  - [The new divisions for chronic patients at Ulleval].

PMID- 14958734
TI  - [Not Available].

PMID- 14958735
TI  - [Prevention of acoustic injury].

PMID- 14958736
TI  - [Amycal compound in therapy of depression; addiction and other risks].

PMID- 14958737
TI  - [Dihydroergotamine therapy of Meniere's diseases and vertigo without demonstrable
      organic etiology].

PMID- 14958738
TI  - [Cortisone therapy of eye diseases].

PMID- 14958739
TI  - [Traumatic polyneuritis after motor cycle riding].

PMID- 14958740
TI  - [Not Available].

PMID- 14958741
TI  - [Prevention of hearing impairment as an occupational disease].

PMID- 14958742
TI  - [Meeting the need for physicians in Norway].

PMID- 14958743
TI  - [National Health Service; arbitration in the conflict between the British Medical
      Association and the Ministry of Health].

PMID- 14958744
TI  - [Factors in infant mortality in Norway].

PMID- 14958745
TI  - [Vitamin D resistant rickets].

PMID- 14958746
TI  - [Dermatomyositis in a 12 year old girl successfully treated with corticotropin
      nyco].

PMID- 14958747
TI  - [Presacral retroperitoneal pneumoradiography].

PMID- 14958748
TI  - [Current problems in diabetes therapy].

PMID- 14958749
TI  - [Vaginal cysts; case report].

PMID- 14958750
TI  - [Poisoning hazards in use of herbicides and insecticides].

PMID- 14958751
TI  - [Barbituism in alcoholists].

PMID- 14958752
TI  - [Anticoagulants in heart diseases].

PMID- 14958753
TI  - [Acetylcholine].

PMID- 14958754
TI  - [Superinfection during antibiotic therapy].

PMID- 14958755
TI  - [Nerve gases].

PMID- 14958756
TI  - [Severe reactions in vaccine therapy of allergy].

PMID- 14958757
TI  - [Stimulation of gastric secretion by a tonic].

PMID- 14958759
TI  - [Malrotation of the intestine].

PMID- 14958758
TI  - [Pseudoachylia gastrica].

PMID- 14958760
TI  - [Rupture of the uterus; case report].

PMID- 14958761
TI  - [Persistent vitelline duct].

PMID- 14958762
TI  - [Late complications after normal labor].

PMID- 14958763
TI  - [Nerve gases].

PMID- 14958764
TI  - [Mental constitution].

PMID- 14958765
TI  - [Barbituric poisoning].

PMID- 14958766
TI  - [Not Available].

PMID- 14958767
TI  - [Dental materials. VI. Porcelain].

PMID- 14958768
TI  - [Compensation methods applied to inlay casting].

PMID- 14958769
TI  - [Tips on preparation of jacket crowns].

PMID- 14958770
TI  - [Indirect inlay in caries therapy and as bridge anchor in vital elements].

PMID- 14958771
TI  - [D. A. van Houte, 25 years in dentistry].

PMID- 14958772
TI  - [J. M. Klinkhamer, Sr., 50 years in dentistry].

PMID- 14958773
TI  - [The course in pedodontia].

PMID- 14958774
TI  - [Dental materials. VII. Steel and stainless steel].

PMID- 14958775
TI  - [Indirect impression technique for inlays with use of reversible hydrocolloids].

PMID- 14958776
TI  - [Sodium and potassium content of saliva].

PMID- 14958777
TI  - [Construction of a peg tooth with binge jointed jacket crown].

PMID- 14958778
TI  - [C. Edmund Kells].

PMID- 14958779
TI  - [Specialism in medicine and dentistry].

PMID- 14958780
TI  - [Abdominal pain in pregnancy].

PMID- 14958781
TI  - [Diseases and abnormalities of the endocrine glands in pregnancy].

PMID- 14958782
TI  - [Uterine cancer].

PMID- 14958783
TI  - [Genital prolapse in newborn].

PMID- 14958784
TI  - [Report on the congress in Bad-Pyrmont].

PMID- 14958785
TI  - [Ultraradical surgery of uterine cancer].

PMID- 14958786
TI  - SYMPOSIUM; retinal detachment.

PMID- 14958787
TI  - Retinal detachment; introduction and definition of terms.

PMID- 14958788
TI  - Retinal detachment; etiology and pathology.

PMID- 14958789
TI  - Retinal detachment; diagnostic and prognostic factors as found preoperative
      examination.

PMID- 14958790
TI  - Treatment of retinal detachments; localization of breaks, description of a
      typical operative procedure.

PMID- 14958791
TI  - Retinal detachment; postoperative care and complications.

PMID- 14958792
TI  - Retinal detachment; evaluation of results of retinal detachment surgery.

PMID- 14958793
TI  - New concepts in the use of ACTH in ophthalmology and otolaryngology.

PMID- 14958794
TI  - Hereditary progressive nerve deafness.

PMID- 14958795
TI  - Improved hearing in congenital auricular malformation; a review of the results
      obtained by surgical methods.

PMID- 14958796
TI  - Certain considerations of the surgical treatment of retinal detachment.

PMID- 14958797
TI  - Zygomatic fracture-dislocations.

PMID- 14958798
TI  - Fractures of the maxilla.

PMID- 14958799
TI  - Fractures of the nasal bones.

PMID- 14958800
TI  - Internal fixation of severe jaw fractures with steel pins.

PMID- 14958802
TI  - Soft tissue wound repair.

PMID- 14958801
TI  - Sinus complications of facial bone injuries and their management.

PMID- 14958803
TI  - Diagnosis and surgical treatment of fractures of the orbit.

PMID- 14958804
TI  - Electronic flash attachment for clinical photography.

PMID- 14958805
TI  - Peripheral iridectomy in narrow angle glaucoma.

PMID- 14958806
TI  - Microwave diathermy in ophthalmology: the various diathermy currents used in
      ophthalmology.

PMID- 14958807
TI  - Microwave diathermy in ophthalmology: clinical evaluation.

PMID- 14958808
TI  - Binocular indirect ophthalmoscopes; the trotterscope and the heed-scope.

PMID- 14958809
TI  - What we have learned about the physiology of hearing as the result of the
      fenestration operation.

PMID- 14958810
TI  - Bone conduction advances following fenestration surgery.

PMID- 14958811
TI  - Neuroanatomy and neurophysiology in the cochlea.

PMID- 14958812
TI  - Triangular cupped laryngeal forceps.

PMID- 14958814
TI  - Atlases of pathology.

PMID- 14958813
TI  - The use of cortisone in otosclerosis.

PMID- 14958815
TI  - IMPORTED tonometers.

PMID- 14958816
TI  - Visual health maintenance at an atomic energy laboratory.

PMID- 14958817
TI  - Compensation problems.

PMID- 14958818
TI  - Sub-division of some Southern Indian communities according to the incidence of
      sickle-cell trait and blood groups.

PMID- 14958819
TI  - Animal-man relationship in tropical diseases in Africa.

PMID- 14958820
TI  - A health, nutrition and parasitological survey in a rural village (Keneba) in
      west Kiang, Gambia.

PMID- 14958821
TI  - The origin, fate and significance of the umbilical hernia in Nigerian children (a
      review of 1,300 cases).

PMID- 14958822
TI  - Antrypol in the treatment of onchocerciasis.

PMID- 14958823
TI  - Planning the control of sleeping sickness; a sequel.

PMID- 14958824
TI  - Immunity to yellow fever nine years after vaccination with 17D vaccine.

PMID- 14958825
TI  - The analysis of the sporozoite rate.

PMID- 14958826
TI  - Summary of recent abstracts. VI. Plague.

PMID- 14958827
TI  - [In memory of Otto Koch].

PMID- 14958828
TI  - [To Wilhelm Kremer on his 65th birthday].

PMID- 14958829
TI  - [The pathology of the tuberculosis of the lymphatic system].

PMID- 14958830
TI  - [Conteben fatalities after thoracoplasty].

PMID- 14958831
TI  - [Peroral cobalt-iron therapy of infectious anemia in pulmonary tuberculosis].

PMID- 14958832
TI  - [Frontal tomography, an important additional aid in the diagnosis of pulmonary
      cavities].

PMID- 14958833
TI  - [Pleomorphic growth and cyclic multiplication of a strain of Mycobacterium
      gallinaceus].

PMID- 14958834
TI  - [Ultrasonic therapy of pleural effusion].

PMID- 14958835
TI  - [Diagnosis of bronchopleural fistula].

PMID- 14958836
TI  - [Differential diagnosis of intrathoracic cavities].

PMID- 14958837
TI  - [Apophysitis of the iliac crest; a contribution on the differential diagnosis of
      deep-seated tuberculosis of the spine in children].

PMID- 14958838
TI  - [Selfcritics].

PMID- 14958839
TI  - [33. meeting of the German Radiology Society in Baden-Baden].

PMID- 14958840
TI  - [In memory of Rudolph Brauer].

PMID- 14958841
TI  - [Interlobar exsudation of middle lobe infiltration].

PMID- 14958842
TI  - [Interstitial pneumonitis].

PMID- 14958843
TI  - [Pseudocavities].

PMID- 14958844
TI  - [Investigations on the enzymatic activity of streptokinase-streptodornase].

PMID- 14958845
TI  - [Capillary permeability in pulmonary tuberculosis; correlation to postoperative
      bleeding after pneumolysis].

PMID- 14958846
TI  - [Development of resistance of m. tuberculosis].

PMID- 14958847
TI  - [Development of tuberculosis in children in postwar time; with special reference
      to therapeutic measures].

PMID- 14958848
TI  - [Determination of sensitivity to streptomycin].

PMID- 14958849
TI  - [Viewpoints in classifying tuberculosis as an occupational disease].

PMID- 14958850
TI  - [Clinical diagnosis of pulmonary tuberculosis and pathologic anatomy].

PMID- 14958851
TI  - [Mesenchymal reaction and course of tuberculosis].

PMID- 14958852
TI  - [Therapy of cavitations].

PMID- 14958853
TI  - [Blood pressure and prognosis in pulmonary tuberculosis].

PMID- 14958854
TI  - [Blood silicate level in pulmonary diseases].

PMID- 14958855
TI  - [Maurer's method of chemotherapeutic tamponade of cavities].

PMID- 14958856
TI  - [Intracavernous application of conteben in pulmonary tuberculosis; preliminary
      report].

PMID- 14958857
TI  - [A case of streptomycin-dermatitis].

PMID- 14958858
TI  - [Improved, ready culture media for Mycobacterium tuberculosis].

PMID- 14958859
TI  - [Evaluation of various concentration-methods for the proof of tubercle bacteria
      in sputum. (Velicogna, bruasol, sputosol)].

PMID- 14958860
TI  - [Tomography in spinal tuberculosis].

PMID- 14958861
TI  - [Bacteriological investigation in the environment of patients with active
      tuberculosis].

PMID- 14958862
TI  - [The effect of triaethylenglykol on mycobacteria].

PMID- 14958863
TI  - [Mediastinal surgery].

PMID- 14958864
TI  - [Enervation of the carotid body in chronic evolutive polyarthritis].

PMID- 14958865
TI  - [Cortisone and ACTH therapy in a case of Felty's syndrome].

PMID- 14958866
TI  - [Endemiology of tuberculosis in Turkey].

PMID- 14958867
TI  - [An unusual complication of gastrointestinal intubation with a mercury-weighted
      tube].

PMID- 14958868
TI  - [Pneumonectomy in a case of pulmonary cancer].

PMID- 14958869
TI  - [Two cases of plastic operations for vesicovaginal fistulas].

PMID- 14958870
TI  - [Etiology of rheumatism].

PMID- 14958871
TI  - [Radiologic aspects of primary pulmonary infection in children and young
      persons].

PMID- 14958872
TI  - [Treatment of a case of pulmonary abscess by lobectomy].

PMID- 14958873
TI  - [A case of otogenic brain abscess].

PMID- 14958874
TI  - [Lumbar sympathectomy and excision of the adrenal medulla in cases of Buerger's
      disease].

PMID- 14958875
TI  - [Renal function in pernicious anemia].

PMID- 14958876
TI  - [Influence of morphine in the radiologic diagnosis of a case of peptic ulcer].

PMID- 14958877
TI  - [Peculiar features in two cases of hemiplegia].

PMID- 14958878
TI  - [The role of perforated tuberculous lymph nodes in the pathogenesis of pulmonary
      tuberculosis].

PMID- 14958879
TI  - [General view on the medical system in Soviet Russia].

PMID- 14958880
TI  - [An unusual case of tumor of the gasserian ganglion].

PMID- 14958881
TI  - [A case of thromboangiitis obliterans failing to improve on adrenalectomy].

PMID- 14958882
TI  - [Ureterointestinal anastomosis in inoperable cases of cancer of the bladder].

PMID- 14958883
TI  - [Results of the systematic radiological examination of 50,000 subjects at the
      Istanbul Tuberculosis Prevention Center].

PMID- 14958884
TI  - [A case of arachnoiditis simulating a tumor of the right cerebellopontile angle].

PMID- 14958885
TI  - [Tuberculosis and hemorrhagic diathesis].

PMID- 14958886
TI  - [Correction of protruding ears].

PMID- 14958887
TI  - [Treatment of nasal fracture].

PMID- 14958888
TI  - [Osteosynthesis of patellar and olecranal fractures].

PMID- 14958889
TI  - [Pituitary implantation in chronic polyarthritis, clinical cases].

PMID- 14958890
TI  - [Furacin ear drops].

PMID- 14958891
TI  - [Choroid detachment following eye contusion, with consideration of invagination
      of the sclera and pigmented stripes in the retina].

PMID- 14958892
TI  - Monaural speech audiometry. Introductory investigations using Danish language
      material with a view to its employment in clinical audiology.

PMID- 14958893
TI  - [Recurrent light hydrocyanic acid poisoning].

PMID- 14958894
TI  - [Reconstructive surgery].

PMID- 14958895
TI  - [Nationwide survey of general morbidity in Denmark].

PMID- 14958896
TI  - [Not Available].

PMID- 14958897
TI  - [Diabetes mellitus mortality in Denmark 1947-49].

PMID- 14958898
TI  - [Causes of death in diabetes mellitus].

PMID- 14958899
TI  - [Burian's antistina therapy in certain types of vertigo and migraine].

PMID- 14958900
TI  - [Ether anesthesia in asthma therapy].

PMID- 14958901
TI  - [Thrombopenia in liver disease; a case of liver cirrhosis with severe
      thrombopenia and esophageal varices].

PMID- 14958902
TI  - [A case of myxedema with predominantly mental symptoms].

PMID- 14958903
TI  - [A case of sodium bicarbonate poisoning with symptomatic tetany and ECG changes].

PMID- 14958904
TI  - [Caries incidence in children 2-6 years of age].

PMID- 14958905
TI  - [Aniline poisoning].

PMID- 14958906
TI  - [Prevention of diabetes].

PMID- 14958907
TI  - [Authorized requirements for teachers of aphasic children].

PMID- 14958908
TI  - [Housing problems exist also in rural regions].

PMID- 14958909
TI  - [Narcotic poisoning; statistical review].

PMID- 14958910
TI  - [Clinical treatment of severe poisoning by hypnotics].

PMID- 14958911
TI  - [Results in recent therapy of poisoning by hypnotics].

PMID- 14958912
TI  - [Barbiturate blood levels in patients at admission to a medical department].

PMID- 14958913
TI  - [Barbituric acid poisoning and ACTH].

PMID- 14958914
TI  - [The unconscious patient].

PMID- 14958915
TI  - [Convulsions and psychoses due to abstinence in chronic barbiturate poisoning].

PMID- 14958916
TI  - [Blood and spinal phenemal levels in epilepsy therapy].

PMID- 14958917
TI  - [Two severe cases of complicated carbon monoxide poisoning].

PMID- 14958918
TI  - [Corneal sensitivity with special reference to clinical diagnostic methods].

PMID- 14958919
TI  - [The hazards of barbituric acids].

PMID- 14958920
TI  - [Medical services in young people's summer camps].

PMID- 14958921
TI  - [Statistics of induced abortions in Denmark 1940-50].

PMID- 14958922
TI  - In memoriam, Valdemar Poulsen.

PMID- 14958923
TI  - [The effect of the universal light bath on immunity].

PMID- 14958924
TI  - [Preventricular bi-frontal leucotomy].

PMID- 14958925
TI  - [Lung function determination in clinical practice].

PMID- 14958926
TI  - [Surgical scrub].

PMID- 14958927
TI  - [Our hospitals].

PMID- 14958928
TI  - [Not Available].

PMID- 14958929
TI  - [Tuberculosis morbidity in children before and after organized mass vaccination].

PMID- 14958930
TI  - [Decrease in new tuberculosis cases in Vejle county, 1944-50].

PMID- 14958932
TI  - [Biological warfare].

PMID- 14958931
TI  - [Tuberculosis in children; a comparison of patients hospitalized 1940 and 1950].

PMID- 14958933
TI  - Diabetes and pregnancy; blood sugar of newborn infants during fasting and glucose
      administration.

PMID- 14958934
TI  - [Tuberculosis in children].

PMID- 14958935
TI  - [Incidence of pulmonary tuberculosis in rural and urban communities 1944-50].

PMID- 14958936
TI  - [Legally induced abortions].

PMID- 14958937
TI  - In memoriam Hans Chr. Jensen.

PMID- 14958938
TI  - [Neuropsychiatric symptoms in the general adaptation system].

PMID- 14958939
TI  - [Exposed treatment of burns].

PMID- 14958940
TI  - [Schizophrenia in children with report on 2 cases].

PMID- 14958941
TI  - [Oral penicillin therapy in ecthyma gangraenosa infantum; case].

PMID- 14958942
TI  - [Fatal case of Herxheimer reaction in penicillin therapy of tertiary syphilis].

PMID- 14958943
TI  - [Holger Nielsen's technique in artificial respiration].

PMID- 14958944
TI  - [Barbituric acid poisoning and heat regulation].

PMID- 14958945
TI  - [Poisoning by aromatic amino- and nitro compounds].

PMID- 14958946
TI  - [Standard nutrition in children's homes].

PMID- 14958947
TI  - [Ambulant electroencephalography in Sygekasselaegernes organisations
      laboratorium].

PMID- 14958948
TI  - [Isonicotinic acid hydrazide therapy of pulmonary tuberculosis].

PMID- 14958949
TI  - [Erythromyelosis (Gulielmo's disease); review and report on case in a benzene
      worker].

PMID- 14958950
TI  - [X-ray therapy of kerion celsi].

PMID- 14958951
TI  - [Prothrombin time fluctuations in newborn with an analysis of the technique and
      evaluation of prothrombin time determination].

PMID- 14958952
TI  - [Chemotherapy of tuberculosis].

PMID- 14958953
TI  - [Housing, disease and induced abortion in the light of material from
      Modrehjelpen].

PMID- 14958954
TI  - [Chemical contraceptives. II].

PMID- 14958955
TI  - [Therapeutic effects of reduced penicillin dosage].

PMID- 14958956
TI  - [A case of gold dermatitis with negative BAL therapy, improved by sodium
      thiosulfate].

PMID- 14958957
TI  - [Tuberculosis in childhood. II..].

PMID- 14958958
TI  - [Ambulant physical therapy].

PMID- 14958959
TI  - Epilepsy in association with intracranial tumour.

PMID- 14958960
TI  - [Chronic manganese poisoning].

PMID- 14958961
TI  - [Chemical contraception].

PMID- 14958962
TI  - [Problematic aspects of a rural practice].

PMID- 14958963
TI  - [Hunting grounds of roaming morphinists].

PMID- 14958964
TI  - [Tuberculosis in Greenland].

PMID- 14958965
TI  - [Tuberculin testing and Calmette vaccinations in Godthaab og Fredrikshaab medical
      districts, Greenland, 1949].

PMID- 14958966
TI  - [Observations during a survey of school children in Umanak 1950-51].

PMID- 14958967
TI  - [An outbreak of paratyphoid B in Godthaab medical district, Greenland].

PMID- 14958968
TI  - [Ichthyosis vulgaris, onychogryposis, Dupuytren's contracture and favus in
      Greenland].

PMID- 14958969
TI  - [Vitamin C deficiency in Greenland].

PMID- 14958970
TI  - [Diseases in Greenland].

PMID- 14958971
TI  - [Eradication of gonorrhea in a medical district in Greenland].

PMID- 14958972
TI  - [Mass therapy of scabies; report from Poland].

PMID- 14958973
TI  - [Mutal antagonism of aureomycin and penicillin].

PMID- 14958974
TI  - [Diethylstilbestrol therapy of orchitis in epidemic parotitis].

PMID- 14958975
TI  - [Prof. Ege's principles for reducing].

PMID- 14958976
TI  - [Comments on x-ray therapy of kerion celsi].

PMID- 14958977
TI  - [Tuberculosis in Greenland].

PMID- 14958978
TI  - [Legislation regarding professional secrecy of attorneys and physicians].

PMID- 14958979
TI  - In memoriam Johannes Paulsen.

PMID- 14958980
TI  - [Cortisone therapy of adrenal hyperplasia].

PMID- 14958981
TI  - [Misdiagnosis of idiopathic hypoparathyroidism].

PMID- 14958982
TI  - [Dermatomyositis with hypertrichosis and polycystic ovarian degeneration].

PMID- 14958983
TI  - [The effectivity of podophyllin in verruca acuminata therapy].

PMID- 14958984
TI  - [Review of nutrition studies 1952].

PMID- 14958985
TI  - [Pediatric endocrinology].

PMID- 14958986
TI  - [Health survey of the population of Denmark].

PMID- 14958987
TI  - [The development of hospital functions and administration].

PMID- 14958988
TI  - A new local treatment of burns.

PMID- 14958989
TI  - Pain Mechanisms: a review.

PMID- 14958990
TI  - The sedimentation rate in acute cholecystitis.

PMID- 14958992
TI  - Mosquito survey of Guam.

PMID- 14958991
TI  - Correction of temporomandibular disturbances by jaw repositioning.

PMID- 14958993
TI  - Some practical clinical aspects of leprosy.

PMID- 14958994
TI  - Planning and designing removable partial dentures. II.

PMID- 14958995
TI  - Gait training for the above-the knee amputee.

PMID- 14958996
TI  - Air transportation of acute poliomyelitic patients.

PMID- 14958997
TI  - The identification and handling of the dead.

PMID- 14958998
TI  - Treatment of Malaria with cortisone.

PMID- 14958999
TI  - Fatal lead poisoning simulating poliomyelitis.

PMID- 14959000
TI  - The clinical aspects of appendicitis.

PMID- 14959001
TI  - Cortisone in the treatment of Friedlander's pneumonia.

PMID- 14959002
TI  - Right lower quadrant pain.

PMID- 14959003
TI  - Sensitivity to ointments containing wool fat.

PMID- 14959004
TI  - Tetanus treated with cortisone.

PMID- 14959005
TI  - Adaptation to Stryker frame.

PMID- 14959007
TI  - A hundred years of progress in urology.

PMID- 14959006
TI  - AVERAGE hospital stay for disability cases lowered in 1951.

PMID- 14959008
TI  - [Preoperative care and anesthesia in extensive operations].

PMID- 14959009
TI  - [Prevention of wound infection with penicillin and sulfanilamides].

PMID- 14959010
TI  - [Penicillin in the treatment and prevention of peritonitis].

PMID- 14959011
TI  - [Graphic registration of the gastric function in peptic ulcer and its changes
      following surgery].

PMID- 14959012
TI  - [Fluorescein test in surgical practice].

PMID- 14959013
TI  - [Determination of dimensions of removed portions of the stomach].

PMID- 14959014
TI  - [Surgical therapy of cancer of the cardia and the lower portion of the
      esophagus].

PMID- 14959015
TI  - [Ovarian rupture and acute appendicitis].

PMID- 14959016
TI  - [Roentgenologic investigation of the bile ducts during surgery of the biliary
      tract].

PMID- 14959017
TI  - [Function of the abdominal muscles as a factor in selection of surgical technic
      in inguinal hernia].

PMID- 14959018
TI  - [Gertsen's operation and its modification in congenital cerebral hernia].

PMID- 14959019
TI  - [Pathogenesis of appearance of trophic disorders in gun-shot injuries of the
      sciatic nerve].

PMID- 14959020
TI  - [Appendicitis on the left side].

PMID- 14959021
TI  - [Left side appendicitis with transposition of the viscera].

PMID- 14959022
TI  - [Case of acute cholecystitis in a two-year-old child].

PMID- 14959023
TI  - [Unusual variation of closed hepatic wound].

PMID- 14959024
TI  - [Unusual localization of fecal fistula with atypical course].

PMID- 14959025
TI  - [Primary tumors of the ureter].

PMID- 14959027
TI  - [Pathogenesis of primary glaucoma according to the Pavlovian theory].

PMID- 14959026
TI  - [Result of investigation on the problem of glaucoma based on the Pavlovian
      theory].

PMID- 14959028
TI  - [Origin of spherical ocular refraction in man].

PMID- 14959029
TI  - [Treatment of so-called allergic diseases of the eye with sodium hyposulfite].

PMID- 14959030
TI  - [Indirect roentgenotherapy of unveal tuberculosis].

PMID- 14959031
TI  - [Diathermocoagulation of suppurative ulcers of the cornea].

PMID- 14959032
TI  - [Diathermocoagulation of suppurative ulcers of the corneal membrane].

PMID- 14959033
TI  - [Result of the treatment of epitheliomas of the eyelids with Gordeev's solution].

PMID- 14959034
TI  - [Pathogenesis of free cysts of the anterior ocular chamber and their surgery].

PMID- 14959035
TI  - [Double blood supply to the retina].

PMID- 14959036
TI  - [Result of work of an ophthalmologist the polyclinic of the Orekhovo-Zuevsk
      cotton paper plant].

PMID- 14959037
TI  - [Result of the ophthalmological survey of collective farms workers along the
      lower part of the North Crymean Canal].

PMID- 14959038
TI  - [Iridocyclitis due to gangrene of the tooth].

PMID- 14959039
TI  - [Repeated paracentesis of the cornea in the treatment of cataract].

PMID- 14959040
TI  - [In memory of Konstantin Khrisanfovich Orlov].

PMID- 14959041
TI  - [Problems of the conduct of otolaryngologist and his relation to patients].

PMID- 14959042
TI  - [Dynamic changes of hearing in tumors of the posterior cranial fossa and their
      interpretation according to Vvedenskii's theory on parabiosis].

PMID- 14959043
TI  - [Role and significance of reflexogenic symptoms in functional deafness according
      to the Pavlovian theory].

PMID- 14959044
TI  - [Significance of auditory and vestibular function in hypertension in
      otolaryngological practice].

PMID- 14959045
TI  - [Fenestration in otosclerosis].

PMID- 14959046
TI  - [Penicillin therapy of otitis due to scarlet fever].

PMID- 14959047
TI  - [Clinical aspects and therapy of diseases of the accessory sinuses of the nose in
      children].

PMID- 14959048
TI  - [Significance of roentgenography in the diagnosis of diseases of the accessory
      sinuses of the nose in infants].

PMID- 14959049
TI  - [Complications in puncture of the maxillary sinus].

PMID- 14959050
TI  - [Diagnosis of laryngitis in children].

PMID- 14959051
TI  - [Intratracheal administration of penicillin].

PMID- 14959052
TI  - [Application of Gordeev's solution in certain forms of scleroma of the upper
      respiratory tract].

PMID- 14959053
TI  - [Data of the study of prolonged observation of patients with scleroma].

PMID- 14959054
TI  - [Needle for endonasal application of sutures to the mucous membranes of the nasal
      septum].

PMID- 14959055
TI  - [Method of stoppage of postoperative hemorrhages in tonsillectomy].

PMID- 14959056
TI  - [Method of stoppage of hemorrhage in tonsillectomy].

PMID- 14959057
TI  - [Aerosol anesthesia in bronchoscopic examination].

PMID- 14959058
TI  - [Anesthesia of the middle ear with the aid of iontophoresis in surgery of aural
      cavity].

PMID- 14959059
TI  - [Method of alloplasty].

PMID- 14959060
TI  - [Atypical course of naso-maxillary tumor].

PMID- 14959061
TI  - [Unusual cranio-facial abnormality].

PMID- 14959062
TI  - [Cases of goiter of the lingual root].

PMID- 14959063
TI  - [Case of laryngeal cancer associated with pseudobulbar paralysis of the recurrent
      nerves].

PMID- 14959064
TI  - [Multiple hemorrhagic pseudosarcomatosis with laryngeal and pharyngeal
      complications].

PMID- 14959065
TI  - [Case of tracheal and bronchial foreign bodies].

PMID- 14959066
TI  - [Unusual esophageal foreign body].

PMID- 14959067
TI  - [Treatment of trepanation wounds of the mastoid process by application of
      secondary sutures].

PMID- 14959068
TI  - [Sub-periosteal administration of penicillin in acute otitis and mastoiditis due
      to scarlet fever].

PMID- 14959069
TI  - [Cerebral abscess, otogenous meningitis, and extradural abscess in pregnancy;
      cure].

PMID- 14959070
TI  - [Cholesteatoma in hypoplasia of the middle ear].

PMID- 14959071
TI  - [Cancer of the middle ear].

PMID- 14959072
TI  - [Three cases of osteoma of the accessory sinuses of the nose].

PMID- 14959073
TI  - [Case of thrombosis of the cavernous sinus of nasal origin].

PMID- 14959074
TI  - [Simplified method of application of plastmass AKR-7 in surgical repair of nasal
      deformities].

PMID- 14959075
TI  - [Tracheotomy following respiratory arrest].

PMID- 14959076
TI  - [Cases of malignant tumors of otorhinolaryngological organs in children and young
      adults].

PMID- 14959077
TI  - [Possible utilization of cutaneous reactions in diagnosis of scleroma of the
      respiratory tract].

PMID- 14959078
TI  - [Consent for surgery].

PMID- 14959079
TI  - [Current function tests and treatment of liver insufficiency; biochemical
      aspects].

PMID- 14959080
TI  - [Current function tests and treatment of liver insufficiency; biological test].

PMID- 14959081
TI  - [Current functions tests and treatment of liver insufficiency; laboratory tests
      and therapy].

PMID- 14959082
TI  - [Current function tests and treatment of liver insufficiency; added information].

PMID- 14959083
TI  - [Current function tests and treatment of liver insufficiency; conclusions].

PMID- 14959084
TI  - [The Leiner-Moussous syndrome (erythrodermia desquamativum of the newborn].

PMID- 14959085
TI  - [Gynecology and constipation].

PMID- 14959086
TI  - [Ketoaciduria and ketoacidosis].

PMID- 14959087
TI  - [Situs inversus viscerum].

PMID- 14959088
TI  - [Doctor Julien Hubert elected honorary member of the Academy of Medicine].

PMID- 14959089
TI  - [Election of doctor Marquezy to the Academy of Medicine].

PMID- 14959090
TI  - [Professor H. Hartmann (1860-1952)].

PMID- 14959091
TI  - [Dean Lucien Cornil].

PMID- 14959092
TI  - [Indicator investigations of the kidneys with triphenyltetrazoliumchloride; on
      the so-called acute nephrosis].

PMID- 14959093
TI  - [Effects of desoxycorticosterone acetate on the testes of normal and
      hypophysectomized rats].

PMID- 14959094
TI  - [Mechanism of entrance of newly formed blood cells from the bone marrow into the
      blood circulation].

PMID- 14959095
TI  - [Electroshock causing disturbances of cerebral blood supply].

PMID- 14959096
TI  - [Angiomyomatosis of the lungs with honeycomb structure].

PMID- 14959097
TI  - [Generalized hematogenous arterial metastasis or carcinoma cell sepsis of a
      seminoma].

PMID- 14959098
TI  - [Vacuolar fatty degeneration of the myocardial fibers].

PMID- 14959099
TI  - [Atrophy and scar tissue formation in teratoids of the testes with generalized
      malignant metastases].

PMID- 14959100
TI  - [Cardiac changes in experimental tuberculosis; comments on infectious-allergic
      inflammation].

PMID- 14959101
TI  - [Observations on two hundred years old people].

PMID- 14959102
TI  - [Biliary xanthomatosis in adults and children; acquired pericholangitic biliary
      cirrhosis].

PMID- 14959103
TI  - [Blood supply of the nerve stem in pathology].

PMID- 14959104
TI  - [New data on reinnervation of injured peripheral nerves].

PMID- 14959105
TI  - [Surgical treatment of peripheral paralysis of the facial nerve; anastomosis of
      the facial nerve with accessory].

PMID- 14959106
TI  - [Result of physiological analysis in clinical neurosurgery].

PMID- 14959107
TI  - [Histochemical study on glycogen content in arachnoid endothelioma].

PMID- 14959108
TI  - [Certain new problems in the study of intracranial hypertension in cerebral
      tumors].

PMID- 14959109
TI  - [Observation on conditions of the cardiovascular system in tractotomy].

PMID- 14959110
TI  - [Collateral circulation in experimental section of the saphenous nerve;
      roentgenovasographic study].

PMID- 14959111
TI  - [Electrophysiological changes in the cortex of the large hemisphere in olfactory
      stimulation].

PMID- 14959113
TI  - [Standard lead of the ERG].

PMID- 14959112
TI  - [Principles in organization of neurosurgical services in outlying districts].

PMID- 14959114
TI  - [Cooperation of psychologist and psychiatrist in psychohygiene in industry].

PMID- 14959115
TI  - [Present status of individual psychology].

PMID- 14959116
TI  - [Transfer and countertransfer].

PMID- 14959117
TI  - [Varicosis spinalis and myelitis].

PMID- 14959118
TI  - [Report from the 3. Lindau Psychotherapy Week, 1952].

PMID- 14959119
TI  - [Demonstration of a new factor in blood coagulation: factor VII].

PMID- 14959120
TI  - [Physiology of cobalt and its derivatives].

PMID- 14959121
TI  - [Physiology of liver glycogen during sympathetic block with hydergin].

PMID- 14959122
TI  - [A case of periodically relapsing toxoplasmosis in adults].

PMID- 14959123
TI  - [Myocardial infarction in aged].

PMID- 14959124
TI  - [Effects of tetraethylammonium].

PMID- 14959125
TI  - [Free motility of the pleural sinus after pleurisy].

PMID- 14959126
TI  - [Investigation of the white blood count and reticulocytes in high mountains].

PMID- 14959127
TI  - [Clinical investigation of the circulatory effect of hyperthermic baths].

PMID- 14959128
TI  - [Blood glycogen level after fructose administration in man].

PMID- 14959129
TI  - [Clinical application of diathermy to the diencephalon and the pituitary].

PMID- 14959130
TI  - [Staub-Traugott's glucose test in patients with gastric resection].

PMID- 14959131
TI  - [Bone marrow findings in rheumatic patients; effects of emanatorium therapy in
      Boeckstein near Badgastein].

PMID- 14959132
TI  - [The problem of monocytes].

PMID- 14959133
TI  - [Photoelectric colorimetry].

PMID- 14959134
TI  - [Vienna Internal Medicine Society].

PMID- 14959135
TI  - [Electromyography of rotatory nystagmus].

PMID- 14959136
TI  - [Bifocal group therapy in Schizophrenia].

PMID- 14959137
TI  - [Brain tumor and pregnancy].

PMID- 14959138
TI  - [Early embryonal arginencephaly in man; pathogenesis of cyclopia].

PMID- 14959139
TI  - [Central posttraumatic diabetes].

PMID- 14959140
TI  - [Tactile allesthesia in spinal diseases].

PMID- 14959141
TI  - [Angioma of the medulla oblongata].

PMID- 14959143
TI  - [Anxiety, a factor hostile and friendly to life; a medico-psychological study].

PMID- 14959142
TI  - [Diffuse, symmetric calcifications in the brain; idiopathic, non
      arteriosclerotic, intracerebral blood vessel calcifications of Fahr].

PMID- 14959144
TI  - [A peculiar lethal complication of a degenerative disc disease].

PMID- 14959145
TI  - [Demonstration of a case of spinal cord tumor].

PMID- 14959146
TI  - What is the international roentgen?

PMID- 14959147
TI  - Improving radiographic quality during hip-nailing operations.

PMID- 14959148
TI  - Principles of fracture roentgenography.

PMID- 14959149
TI  - Arteriograms; open versus closed method.

PMID- 14959150
TI  - Roentgenologic apparatus attachable to the Bell fracture table.

PMID- 14959151
TI  - Positioning in lateral radiography of the first three dorsal vertebrae.

PMID- 14959152
TI  - Medical writing; selections from a teacher's lecture notes.

PMID- 14959153
TI  - AMERICAN Society of X-Ray Technicians; twenty-fourth annual convention.

PMID- 14959154
TI  - The technician instructor.

PMID- 14959155
TI  - Survey of data obtained from the annual reports of the approved schools of x-ray
      technology.

PMID- 14959156
TI  - An x-ray protection device.

PMID- 14959157
TI  - Studies on schistosome dermatitis kabure caused by the cercariae of Schistosoma
      japonicum.

PMID- 14959158
TI  - A series of investigations into myopia. Report I. The refractive state of primary
      pupils before and after the instillation of atropine.

PMID- 14959159
TI  - P.V.L. treatment of lymphogranuloma venereum.

PMID- 14959160
TI  - Beitrag zur Morphologie des Ligamentum capitis femoris.

PMID- 14959161
TI  - On a simplified hemagglutination reaction in tuberculosis; a hollow agglutination
      plate method.

PMID- 14959162
TI  - On a result of hemagglutination test for tuberculosis in cows.

PMID- 14959163
TI  - [Unification of health services].

PMID- 14959164
TI  - [Unified health services].

PMID- 14959165
TI  - [Report from the Znojmo district].

PMID- 14959166
TI  - [Collection of the blood outside banks and collecting stations].

PMID- 14959167
TI  - [Instructions concerning the national blood transfusion service].

PMID- 14959168
TI  - [Legislations, orders, and instructions].

PMID- 14959169
TI  - [Occupational diseases in rural areas].

PMID- 14959170
TI  - [Resolution at the biological and medical conference].

PMID- 14959171
TI  - [International conference on child welfare].

PMID- 14959172
TI  - [Nurseries in Czechoslovakia].

PMID- 14959173
TI  - [Health services in the USSR].

PMID- 14959174
TI  - [Legislations, laws and instructions].

PMID- 14959175
TI  - [Hygienic and epidemiologic services in the USSR].

PMID- 14959176
TI  - [Significance of pathogenesis in the clinical practice].

PMID- 14959177
TI  - [Practical method of investigation of vegetative disorders in the pathogenesis of
      rheumatism].

PMID- 14959178
TI  - [Prothrombin time and factor V].

PMID- 14959180
TI  - [Tuberculous meningitis].

PMID- 14959179
TI  - [Cardiac aneurysm].

PMID- 14959181
TI  - [Activities of tuberculosis institutions in Slovenia in 1951 and hospitalization
      of tuberculous patients].

PMID- 14959182
TI  - [Progress in the treatment of infectious diseases].

PMID- 14959183
TI  - [War nephritis].

PMID- 14959184
TI  - [Dynamics and elasticity of the contracted skeletal muscle under the influence of
      inforced sinusoid changes of length].

PMID- 14959185
TI  - [Blue and violet looking colors in the red-green blind area of the retina].

PMID- 14959186
TI  - [Effects of electrolytically treated water on tadpoles].

PMID- 14959187
TI  - [Physicochemical findings in hyaline substance of connective tissue].

PMID- 14959188
TI  - [Interpretation of the Pulfrich effect. II. Electrical registration of ocular
      movements during the Pulfrich effect].

PMID- 14959189
TI  - [The length of the standing wave in the brachial artery of man].

PMID- 14959190
TI  - [Investigations of the vaginal portion of the uterus by means of the
      colpomicroscope].

PMID- 14959191
TI  - [Experiences and results in cytological diagnosis of cancer].

PMID- 14959192
TI  - [Genital cancer and pregnancy].

PMID- 14959193
TI  - [The problem of bilateral ovarectomy during pregnancy].

PMID- 14959194
TI  - [Erythrocyte count in the mature newborn].

PMID- 14959195
TI  - [Study of pregnancy, delivery and puerperium in a submucous myoma].

PMID- 14959196
TI  - [Chemotherapy of tuberculosis. IV. Tuberculostatics of inferior effectiveness].

PMID- 14959197
TI  - [Increase of silicic acid blood level and urine excretion in silicosis; their
      evaluation].

PMID- 14959198
TI  - [Nomenclature and role of factors in blood coagulation].

PMID- 14959199
TI  - [Experiences in therapy of progressive muscle dystrophy with glutamic acid].

PMID- 14959200
TI  - [Normal and pathological physiology of the blood. II. Difference of distribution
      of leucocytes in the blood picture slide].

PMID- 14959201
TI  - [Change of functional types of the electrocardiogram under normal conditions].

PMID- 14959202
TI  - [Pathogenesis and therapy of peptic ulcer].

PMID- 14959203
TI  - [General poisoning by arsenic in relation to diencephalon and malnutrition;
      melanosis, polyneuritis, alopecia, liver cirrhosis, chronic nephritis].

PMID- 14959204
TI  - [Precipitability of the blood serum].

PMID- 14959205
TI  - [Determination of cytochrom C in the human muscle].

PMID- 14959206
TI  - [Epidemiological investigations of the poliomyelitis epidemic in Wiesbaden,
      Bermany, 1950].

PMID- 14959207
TI  - [Pharyngeal bacteria in scarlatina treated with penicillin; general therapy of
      scarlatina with penicillin].

PMID- 14959208
TI  - [Serological investigations of diphtheria bacteria].

PMID- 14959209
TI  - [Problems of hygiene of milk].

PMID- 14959210
TI  - [Complement fixation reaction in diagnosis of influenza. I. Production and
      evaluation of influenza antigens].

PMID- 14959211
TI  - [Changes of the antigen structure during the dissociation in Shigella Flexneri
      type 3 (H)].

PMID- 14959212
TI  - [Attempts to neutralize the virus of atypical fowl plague in vaccinated chicken].

PMID- 14959213
TI  - [Prevention of water infection in injection therapy by preservatives].

PMID- 14959214
TI  - [Investigations on the effect of experimental coronary occlusion on the
      circulatory dynamics; clinical importance of Bezold-Jarisch effect].

PMID- 14959215
TI  - [Types of respiratory arrhythmia].

PMID- 14959216
TI  - [The sound picture of congenital cardiovascular abnormalities].

PMID- 14959217
TI  - [Correlations between heart rate and QT period during athletic training].

PMID- 14959218
TI  - [Hypoprothrombinemia in cardiovascular abnormalities].

PMID- 14959219
TI  - [Clinical importance of vibration analysis on heart sound figures in children].

PMID- 14959220
TI  - [The problem of thermo-receptive heart reflexes].

PMID- 14959221
TI  - [Reliability of the ergot test in the differential diagnosis of functional and
      organic ECG changes].

PMID- 14959222
TI  - [Plain fluorescopy in diagnosis of myocardial dysfunction].

PMID- 14959223
TI  - [Large retrograde embolism into the inferior vena cava after experimental
      pulmonary embolism in animals].

PMID- 14959224
TI  - [Local and generalized blood pressure reaction caused by physical effects on the
      upper extremities].

PMID- 14959225
TI  - [Report from the 38. meeting of the Northwest-German Internal Medicine Society,
      Hamburg-Altona, February 8-9, 1952].

PMID- 14959226
TI  - [Hearing aids; evaluation of new apparatus].

PMID- 14959227
TI  - [Surgery of fistula of vestibular apparatus].

PMID- 14959228
TI  - [Streptomycin damages of the vestibular nerve and their healing tendency].

PMID- 14959229
TI  - [Hearing disorders and focal infection].

PMID- 14959230
TI  - [Deafness of aged, an impairment of the hearing tonus; Hypotonia senilis
      acustica].

PMID- 14959231
TI  - [Iodine excretion, a diagnostic measure in diseases of the salivary glands].

PMID- 14959232
TI  - [First International Allergy Congress, Zurich, September 23-29, 1951].

PMID- 14959233
TI  - [Experiences in above-threshold audiometry].

PMID- 14959234
TI  - [Determination of objective hearing figures by means of a modified Stenger's test
      on the audiometer].

PMID- 14959235
TI  - [Follow-up of patients using hearing aides].

PMID- 14959236
TI  - [Importance of x-ray picture in evaluation of the ear].

PMID- 14959237
TI  - [The utriculo-endolymphatic valve].

PMID- 14959238
TI  - [Prevention of deformity of the auricle after perichondritis by use of a supramid
      prosthesis].

PMID- 14959239
TI  - [Morphogenesis of the osseous auditory meatus; its role in pathogenesis of
      cholesteatoma].

PMID- 14959240
TI  - [Course of rhinoscleroma treated with terramycin; histological picture].

PMID- 14959241
TI  - [A new inhalation anesthetic: isopropylchloride].

PMID- 14959242
TI  - [Comparison between the normal hearing with the auditory ossicles and the hearing
      via the cranium].

PMID- 14959243
TI  - [Prof. Carl Springer -- 80 years old on August 3, 1952].

PMID- 14959244
TI  - [Therapy of coxa vara adolescentium].

PMID- 14959245
TI  - [Periarthritis humeroscapularis--caused by spasticity of neck and shoulder
      muscles].

PMID- 14959246
TI  - [Osteochondrosis and periarthritis; differential diagnosis of shoulder pain].

PMID- 14959247
TI  - [Study on the feet of male and female dancers].

PMID- 14959248
TI  - [Way and localization of mycobacterium tuberculosis in infection of the spine].

PMID- 14959249
TI  - [Extraarticular or intraarticular arthrodesis in tuberculous coxitis].

PMID- 14959250
TI  - [Incidence and duration of fistula formation in osteoarticular tuberculosis].

PMID- 14959251
TI  - [Chronic stiffness of the spine caused by muscular spasticity].

PMID- 14959252
TI  - [Experimental investigations in pathology of Hoffa's disease].

PMID- 14959253
TI  - [Isolated fracture of the posterior process of the talus].

PMID- 14959254
TI  - [Experiences in nailing the femur neck in Perthes' disease with Pitzen's method].

PMID- 14959255
TI  - [Therapy of orthopedics in the last 100 years; with reference to problems in
      orthopedics].

PMID- 14959256
TI  - [Deformities of the forefoot; surgical repair of its form and function].

PMID- 14959257
TI  - [Anatomical findings after plastic hip operation with a metal cap].

PMID- 14959258
TI  - [Pathogenesis of lumbal scoliosis].

PMID- 14959259
TI  - [Late picture of hematomyelia caused by birth injury].

PMID- 14959260
TI  - [The problem of meniscus operation].

PMID- 14959261
TI  - [Evipan rectal anesthesia in children].

PMID- 14959262
TI  - [Evaluation of rheumatism as service-connected disability].

PMID- 14959263
TI  - [Rheumatism and accident in medical evaluation].

PMID- 14959264
TI  - [Diagnosis of chronic rheumatic myositis].

PMID- 14959265
TI  - [Serum copper levels in primary chronic polyarthritis].

PMID- 14959266
TI  - [Importance of the system hyaluronic acid-hyaluronidase in rheumatic joint
      diseases].

PMID- 14959267
TI  - [The problem of Brill's diseases seen in the light of new observations and
      investigations].

PMID- 14959268
TI  - [New investigations on Bartonella muris Mayer. II..].

PMID- 14959269
TI  - [New investigations on Bartonella bacilliformis. II. Effects of sulfonamides &
      antibiotics in vitro].

PMID- 14959270
TI  - [Blood parasites of the white mouse. I. Studies on Eperythrozoon coccoides
      Schilling, Dinger].

PMID- 14959271
TI  - [Experimental investigations on murine poliomyelitis virus in ticks (ornithodorus
      moubata)..].

PMID- 14959272
TI  - [Non-stinging flies spreading leptospirae].

PMID- 14959273
TI  - [Possibilities of errors in direct demonstration of parasites in toxoplasmosis].

PMID- 14959274
TI  - [Roentgenodiagnosis of toxoplasmosis].

PMID- 14959275
TI  - [Toxoplasma gondii; investigations on resistance against physical and chemical
      effects].

PMID- 14959276
TI  - [Attempts to infect poikilotherm animals (rana esculentax) and Natrix natrix)
      with toxoplasma gondii].

PMID- 14959277
TI  - [Malaria and diabetes mellitus].

PMID- 14959278
TI  - [Investigations on enterobia (oxyuris). II. Biological viewpoints in human
      enterobiasis].

PMID- 14959279
TI  - [Hookworm infection in hospital practice in Tungkun, South China].

PMID- 14959280
TI  - [Schistosoma japonicum eggs in surgical biopsies].

PMID- 14959281
TI  - Modified setae on the palp of blood sucking midges.

PMID- 14959282
TI  - [Preliminary list of mosquitoes (Uranotaenii, Toxorhynchitni, Culicini, Aedini
      and Sabethini) in Equador (Diptera-Culicidae)].

PMID- 14959283
TI  - [Remembering Kart Landsteiner].

PMID- 14959284
TI  - [Determination of hormones in infectious diseases].

PMID- 14959285
TI  - [Methods of biological tests, with special reference to auxanogramm and tube
      test. I. Methods to verify the auxanogramm method statistically].

PMID- 14959286
TI  - [Experimental investigations on development of bacteriophage. II. Polyvalent
      strains of bacteriophage in intestinal mucus of man and animal].

PMID- 14959287
TI  - [Comparative investigations in diagnosis of salmonella and shigella. I.
      Tetrathionatagar and 2% tetrathionat broth of Preuss, Wilson-Blair agar,
      Desoxycholat agar, and Selenit F broth of Leifson].

PMID- 14959288
TI  - [The problem of demonstration of the dysentery bacilli; on survival of typhoid,
      paratyphoid B and dysentery bacilli in dry condition on paper surface].

PMID- 14959289
TI  - [Vi agglutinin in typhoid fever].

PMID- 14959290
TI  - [Selenit indicator plate, means to differentiate streptococci].

PMID- 14959291
TI  - [A simple culture media for lactobacillus bifidus and acidophilus].

PMID- 14959292
TI  - [Effects of preparation of tuberculous material on demonstration of mycobacterium
      tuberculosis in culture and animal experiment].

PMID- 14959293
TI  - [Demonstration of nuclear equivalents in mycobacterium tuberculosis].

PMID- 14959294
TI  - [Antibacterial substances produced by actinomycetes].

PMID- 14959295
TI  - [Examination of a modification of Gram's stain. (G. J. Hucker's method)].

PMID- 14959296
TI  - [Use of Mesocricetus auratus as a laboratory animal].

PMID- 14959297
TI  - [Parasitic pneumonia. Interstitial plasma cell pneumonia of premature, caused by
      pneumocystis Carinii].

PMID- 14959298
TI  - [Problems of laboratory technique with DDT].

PMID- 14959299
TI  - [NoReport from the 5th Meeting of the German Sociaty for Hygiene and Microbiology
      in Munster/Westphalia, September 11-13, 1951].

PMID- 14959300
TI  - [Biochemistry and immunology of microorganisms and virus].

PMID- 14959301
TI  - [Investigations of antigens and antibodies].

PMID- 14959302
TI  - [Biology of antibodies].

PMID- 14959303
TI  - [Effects of bacterial toxins; biochemical analysis of inflammation].

PMID- 14959304
TI  - [Basic immunity, its non-specifity and epidemiological effects].

PMID- 14959305
TI  - [Formation of active immunity in foot and mouth disease].

PMID- 14959306
TI  - [Effects of the acid. soluble antigens of erysipeloid bacteria in the animal
      experiment].

PMID- 14959307
TI  - [Experimental investigations on the effectiveness of erysipeloid vaccines].

PMID- 14959308
TI  - [Immunebiology of the tubercle bacillus].

PMID- 14959309
TI  - [Experimental investigations on the effectiveness of the tuberculosis
      vaccination].

PMID- 14959310
TI  - [Helminths and immunity].

PMID- 14959311
TI  - [Defense reactions in plants].

PMID- 14959312
TI  - [Action of chemotherapeutics and antibiotics].

PMID- 14959313
TI  - [Replacement theory].

PMID- 14959314
TI  - [Genotypic analysis of erythrocytes].

PMID- 14959315
TI  - [The positive proof of paternity].

PMID- 14959316
TI  - [Reliability of the positive paternity proof with the Loens method].

PMID- 14959317
TI  - [Positive paternity test of Loens].

PMID- 14959318
TI  - [A few basic remarks to the positive paternity proof with the Loens method].

PMID- 14959319
TI  - [The Loens method in determination of heredity].

PMID- 14959320
TI  - [Milk hygiene seen from the viewpoint of the veterinary hygienist].

PMID- 14959321
TI  - [Milk hygiene seen from viewpoint of the human hygienist].

PMID- 14959322
TI  - [Milk hygiene seen from viewpoint of the social hygienist].

PMID- 14959323
TI  - [Necessary measures to obtain hygienic and sanitary milk].

PMID- 14959324
TI  - [Increase of bacteria in dairy milk].

PMID- 14959325
TI  - [Milk hygiene and tuberculosis].

PMID- 14959326
TI  - [Problems of modern milk hygiene and distribution of high quality milk in
      destroyed cities].

PMID- 14959327
TI  - [Mycobacteria of the milk].

PMID- 14959328
TI  - [Sickle cell anemias and anemias of the sickle cell type].

PMID- 14959329
TI  - [The fluorine content of drinking water in the Rheno-Westfalian industrial area].

PMID- 14959330
TI  - [Nomenclature of virus pathogenic for man].

PMID- 14959331
TI  - [Slow adaptation of the cattle virus of foot and mouth disease of type B to the
      mouse brain by several passages].

PMID- 14959332
TI  - [Experimental investigations in the problem of epidemic encephalitis].

PMID- 14959333
TI  - [Investigations on the virus of the pleuropneumonia group and their existence in
      man].

PMID- 14959334
TI  - [Incubation time in experimental animal infections].

PMID- 14959335
TI  - [Pharmacological investigations on the poison of the Flexner dysentery bacilli].

PMID- 14959337
TI  - [Granulomatosis infantiseptica].

PMID- 14959336
TI  - [Enlargement of the collection of the sera of the Paul-Ehrlich Institute].

PMID- 14959338
TI  - [Allergic diseases after letospirosis].

PMID- 14959339
TI  - [Electro-microscopic observations on coli bacilli].

PMID- 14959340
TI  - [Effects of arsenoxide in vitro].

PMID- 14959341
TI  - [Microbiological and energetic considerations].

PMID- 14959342
TI  - [Metabolis analysis of deficiency of mineral salts in green algae].

PMID- 14959343
TI  - [New research on myxobacteria].

PMID- 14959344
TI  - [Destruction of heterocyclic nitrogen compounds by different soil
      microorganisms].

PMID- 14959345
TI  - [Bacterial flagellae, organs for active motion or parts of the external layer].

PMID- 14959346
TI  - [Vital staining of bacterial; effects of antibiotics; cell division (vital
      staining)].

PMID- 14959347
TI  - [Physiology of intracellular symbionts].

PMID- 14959348
TI  - [Use of peridural anesthesia in abdominal surgery].

PMID- 14959349
TI  - [Postoperative gastrointestinal atonia after gastric resection in peridural
      anesthesia].

PMID- 14959350
TI  - [Case report of a pancreatic cyst].

PMID- 14959351
TI  - [Rare, interesting finding in biliary duct operations: (1) stones in the common
      duct without jaundice (2) fistula in the navel region originating from the gall
      bladder].

PMID- 14959352
TI  - [Indication of surgery of rectal prolapse].

PMID- 14959353
TI  - [Intestinal type of thromboangiitis obliterans Winiwarter-Buerger].

PMID- 14959354
TI  - [An unusual type of acute disorder of blood circulation].

PMID- 14959355
TI  - [Technique of plastic joint surgery].

PMID- 14959356
TI  - [Resorption of the suture material collafil].

PMID- 14959357
TI  - [Clinical use of collafil].

PMID- 14959358
TI  - [Value of intracardial neospiran injections].

PMID- 14959359
TI  - [Successfully removed teratoid cyst of the diaphragm].

PMID- 14959360
TI  - [Therapy of epicondylitis humeri with special reference to Hohmann's operation].

PMID- 14959362
TI  - [4. meeting of the Medical-Scientific Surgery Society at the Universtiy of Jena].

PMID- 14959361
TI  - [Experimental and clinical use of fibrin derivatives made of cattle plasma. I.
      Properties of fibrin foam and its experimental use in control of hemorrhage].

PMID- 14959363
TI  - [New knowledge in differential diagnosis and therapeutic indications of hip
      diseases].

PMID- 14959364
TI  - [The bleeding gastric ulcer].

PMID- 14959365
TI  - [Experiences in lung resections].

PMID- 14959366
TI  - [Differential diagnosis and therapy of tumors of the bones].

PMID- 14959367
TI  - [Leukemic changes of the female genitalia].

PMID- 14959368
TI  - [A case of ascending genital actinomycosis cured by modern therapy].

PMID- 14959369
TI  - [Pregnancy in atresic rudimentary accessory horn].

PMID- 14959370
TI  - [A case of extrauterine pregnancy with live infant born at term].

PMID- 14959371
TI  - [Diagnostic problems in a case of uterus bicornis with double neck and double
      vagina with unilateral atresia].

PMID- 14959372
TI  - [Determination of parametrial elasticity with a new instrument].

PMID- 14959373
TI  - [Study on an unusually large hydrosalpinx].

PMID- 14959374
TI  - [Electrodiagnosis in early detection of pregnancy toxemia].

PMID- 14959375
TI  - [Neuroendocrine disorders in relation to cancer etiology and therapy].

PMID- 14959376
TI  - [Use of forceps with rotating handle in labor].

PMID- 14959377
TI  - [Sparteine as oxytocic].

PMID- 14959378
TI  - [Clinical significance of inflammatory changes in material removed in abortion].

PMID- 14959379
TI  - [Active therapy of febrile abortions].

PMID- 14959380
TI  - [Allegedly brief pregnancies].

PMID- 14959381
TI  - [Expert opinion in abnormally brief pregnancy].

PMID- 14959382
TI  - [Supraceillin eye drops in ocular prophylaxis of newborn].

PMID- 14959383
TI  - [Ovarian arrhenoblastoma with malignant recidivation].

PMID- 14959384
TI  - [The krukenberg tumors, a borderline area in gynecological surgery with case
      report].

PMID- 14959385
TI  - [Primary tubal carcinoma; case, with clinical diagnosis].

PMID- 14959386
TI  - [A case of heterologous mixed tumor of the uterus].

PMID- 14959387
TI  - [Ulcers of the higher intestine following x-ray radiation for cervical
      carcinoma].

PMID- 14959388
TI  - [Atypical vascularization in cervical carcinoma].

PMID- 14959389
TI  - [Results of treatment of cervical carcinoma at the Rostock University Gynecology
      Clinic, 1941-1945].

PMID- 14959390
TI  - [Results with sponge biopsy].

PMID- 14959391
TI  - [30 Years of gynecological laparotomy without thrombosis and embolism].

PMID- 14959392
TI  - [Male and female sex hormone therapy of inoperable ovarian carcinoma].

PMID- 14959393
TI  - [Free omental transplantation in gynecological surgery].

PMID- 14959394
TI  - [Primary genital pneumococcus infection].

PMID- 14959395
TI  - [Non-surgical treatment of uterine prolapse].

PMID- 14959396
TI  - [Friedrich Schultze-Rhonhof].

PMID- 14959397
TI  - [Tumor and pregnancy].

PMID- 14959398
TI  - [Autochthonous malaria infection in the last half of pregnancy].

PMID- 14959399
TI  - [Paralysis following severe eclampsia].

PMID- 14959400
TI  - [Causes of tetanic symptoms in pregnancy].

PMID- 14959401
TI  - [Menstruation and pregnancy in relation to surgical borderline problems].

PMID- 14959402
TI  - [Individual antigens as serological cause of fetal injury and their role in blood
      transfusion].

PMID- 14959403
TI  - [Fetal syphilis and erythroblastosis in newborn, with consideration on
      differential diagnosis of both diseases].

PMID- 14959404
TI  - [New observations on diagnosis of intrauterine fetal death].

PMID- 14959405
TI  - [Results of cesarean sections during the past 15 years at Leipzig University
      obstetrical clinic (1177 cesarean sections in 49,273 deliveries)].

PMID- 14959406
TI  - [Athletic competition during pregnancy].

PMID- 14959407
TI  - [The increase of abnormalities in newborn in Berlin during the postwar period].

PMID- 14959408
TI  - [Prostigmine therapy of amenorrhea].

PMID- 14959409
TI  - [Blood tocopherol (vitamin E) in women, especially in climacteric dysfunction].

PMID- 14959410
TI  - [Carbon monoxide poisoning and pregnancy].

PMID- 14959411
TI  - [Abortions of unknown etiology and Rh blood groups].

PMID- 14959412
TI  - [Mental stress in pregnancy as a cause of infant abnormality].

PMID- 14959413
TI  - [A clinically interesting course of a criminal abortion].

PMID- 14959414
TI  - [Reply to K. Nordmeyer's article, frigidity].

PMID- 14959415
TI  - [A method for marking toads].

PMID- 14959416
TI  - [Milieu-conditioned injury of the gonads in man].

PMID- 14959417
TI  - [Gynecological and obstetric significance of urinary secretion of pregnandiol].

PMID- 14959418
TI  - [Opening address of the President of the Academy of Sciences of USSR at the joint
      session of the Academy of Sciences of USSR and the Academy of Medicine of USSR].

PMID- 14959419
TI  - [Functional condition of the cerebral cortex and function of internal organs].

PMID- 14959420
TI  - [Certain conclusions of the conference on physiology].

PMID- 14959421
TI  - [Phase functional modifications of large hemispheres in children].

PMID- 14959422
TI  - [Principles of reversibility in conditioned reflex function].

PMID- 14959423
TI  - [Study on simultaneous function of the first and second signal systems of the
      cerebral cortex].

PMID- 14959424
TI  - [Role of hypnotic and sleep inhibition in the pathogenesis and in the treatment
      of neurotic syndromes].

PMID- 14959425
TI  - [Theory of the higher nervous function and clinical aspects of internal diseases;
      introduction of the Pavlovian theory into the clinical practice].

PMID- 14959426
TI  - [Certain facts and perspectives of cortical and subcortical function tests in
      clinical neurosurgery].

PMID- 14959427
TI  - [Role of higher nervous function disorders in the pathogenesis of hypertension].

PMID- 14959428
TI  - [Certain principal problems in the field of pathophysiology according to the
      Pavlovian theory].

PMID- 14959429
TI  - [Result of the study on the phenomenon of extinction and restoration of cortical
      and subcortical functions in agonal states and resuscitation of the organism].

PMID- 14959431
TI  - [Synapse of the cerebral cortex of the large hemisphere].

PMID- 14959430
TI  - [Relation between the Pavlovian theory and Vvedenskii's theory in the problem of
      inhibition].

PMID- 14959432
TI  - [Decision of the Scientific Council on the Pavlovian theory during the conference
      of the Presidium of the Academy of Science of USSR (12 April, 1951)].

PMID- 14959433
TI  - [Method of investigation of conditioned reflexes in animals].

PMID- 14959434
TI  - [Effect of vitamin B1 on conditioned reflex function in dogs].

PMID- 14959435
TI  - [Effect of phenamine on of the higher nervous function in white rats].

PMID- 14959436
TI  - [Sequelae of anemia of the central nervous system in dogs].

PMID- 14959437
TI  - [Experimental hypertension of cortical origin].

PMID- 14959438
TI  - [Certain data on conditioned reflex to time in lower monkeys (baboons, Macaca,
      and marmoset)].

PMID- 14959440
TI  - [Pavlovian theory on the higher nervous system and problems of etiology].

PMID- 14959439
TI  - [Certain peculiarities of the higher nervous function in ontogenesis of puppies].

PMID- 14959441
TI  - [Pavlovian theory and physical therapy].

PMID- 14959442
TI  - [Pavlovian preventive sleep therapy in pre- and postoperative periods].

PMID- 14959443
TI  - [Therapeutic associated conditioned reactions in chronic alcoholism].

PMID- 14959444
TI  - [Phase conditions of the cerebral cortex in reactive depression].

PMID- 14959445
TI  - [A revised form of the Pavlovian theory].

PMID- 14959446
TI  - [Cardiovascular diseases considered as a problem of medical organization].

PMID- 14959447
TI  - [The child crippled in infancy].

PMID- 14959448
TI  - [Cardiovascular rehabilitation and prevention: the necessary complement to
      current therapy].

PMID- 14959449
TI  - 17 beta-estradiol modulates effects of insulin-induced changes in vascular
      contractility.
AB  - The protective role of estrogens against peripheral vascular and coronary disease
      in women is well documented; however, it is not present in diabetic women.
      Estrogens reduce tension development through non-genomic mechanisms that include
      changes in calcium concentrations in endothelial and smooth muscle cells, and
      regulation of nitric oxide synthase (NOS) in endothelial cells. Insulin increases
      endothelin-1 (ET-1) release from endothelial cells modulating smooth muscle
      calcium levels and elevating force generated by femoral and coronary arteries.
      This paper examines whether 17 beta-estradiol (E2 beta) modulates changes in
      femoral and coronary artery contractility induced by insulin. Femoral and
      coronary arteries were obtained from male Wistar rats, placed in isolated tissue
      baths for in vitro studies, perfused with different solutions, and the
      contractile response to KCl 40 mmol/L was measured. Insulin increased arterial
      contraction induced by KCl. This increase was not present when the endothelium
      was removed. In the presence of E2 beta, we observed a dose dependent reduction
      in the tension developed and this effect disappeared when the endothelium was
      removed. The insulin-induced contraction was significantly reduced in presence of
      E2 beta. These data indicate that the effect of insulin on femoral and coronary
      vascular contractility is modulated by E2 beta.

PMID- 14959450
TI  - Mechanical factors of cardiovascular risk in systemic arterial hypertension. A
      new sign of arterial rigidity.
AB  - ANTECEDENT: By means of sphygmokinetocardiography (SKCG) we developed and
      arterial rigidity index (ARI) which measure the pulse wave aortic carotid
      reflexion time over the left ventricular ejection time (LVET). This index,
      together with the pulse wave velocity (PWV) and the pulse pressure (PP) are
      indicators of arterial stiffness. In this paper we measured these index in 27
      systemic artery hypertension. Cases (group A, GA), with and without left
      ventricular hypertrophy (subgroups: A1 SGA1, n = 13, and A2, SGA2, n = 14),
      respectively, and 28 normotensive cases (group B, GB). PROTOCOL: In two
      occasions: after 3 minutes of sitting position (SP) and after 3 minute of logging
      in an upright position (UP), blood pressure, ARI, PP, PWV (aortic-hand finger
      distance/aorto-hand finger pulse time) and R-IV interval (electrocardiographic R
      wave-left early ventricular kinetocardiography deflexion) were measured. RESULTS:
      Demography was similar in GA and GB. Systolic, diastolic and pulse pressure were
      significantly higher in GA vs GB. LVET (ms) was lower in GA vs GB in SP (268 +/-
      42 vs 274 +/- 40, p < 0.001, respectively) and higher postexercise UP (280 +/- 42
      vs 244 +/- 46, p < 0.001). PWV m/s were higher in SP in GA vs GB (9.8 +/- 2.8 vs
      7.4 +/- 1.2, p < 0.001, respectively) and in UP (10.1 +/- 1.9 vs 7.9 +/- 9, p <
      0.001, respectively). ARI was lower in UP in GA vs GB (0.48 +/- 0.3 vs 0.80 +/-
      0.3, p < 0.003). Correlation index of PP vs SBP, vs DBP and vs PWV were
      significant in SP and in UP. Height had a significant correlation vs ARI in SP
      and UP (r = 0.60, p < 0.01, and r = 0.42, p < 0.05, respectively). CONCLUSION:
      PWV is increased in GA vs GB patients. The ARI index is lower in GA vs GB cases
      in post exercise. PWV and PP showed a statistical significant correlation; height
      vs ARI had also a significant correlation: SKCG is a new method, that uses a not
      commercially instrument, which should have clinical application.

PMID- 14959451
TI  - Tricuspid atresia associated with common arterial trunk and 22q11 chromosome
      deletion.
AB  - The case of a four-months old male with coexistent tricuspid atresia and common
      arterial trunk is presented. The diagnosis was made by cardiac catheterization
      and selective angiocardiography. Clinical considerations are discussed and the
      review of the available literature reveals this patient to be the tenth case
      reported of this very unusual association of cardiovascular defects, and the
      first with positive deletion of the 22q11 chromosome.

PMID- 14959452
TI  - [Radiofrequency ablation of late ventricular tachycardia in patients with
      corrected Tetralogy of Fallot].
AB  - We present the cases of two patients with surgical repaired Tetralogy of Fallot
      and late ventricular tachycardia. In one patient, the ventricular tachycardia had
      a right bundle branch block pattern, and in the other, a left bundle branch block
      pattern. In both patients a macroreentrant circuit in the right ventricular
      outflow tract was documented; radiofrequency ablation was effective in both
      cases. This suggests that the morphology of the ventricular tachycardia in these
      patients could depend of the direction of the circuit into the right ventricular
      outflow tract and that mapping of this zone allows to localize the appropriate
      site for effective ablation.

PMID- 14959453
TI  - [Recurrent left atrial myxoma].
AB  - Primary cardiac tumors are rare. Mixomas are the most common among them; 75% are
      located in the left atrium, 20% in the right atrium, and the rest in the
      ventricles. The seldom appear in atrio-ventricular valves. Recidivant mixoma are
      also rare, appearing in 1-5% of all patients that have undergone surgical
      treatment of a mixoma. In this paper we present our experience with a female
      patient, who 8 years after having been operated of a left atrial mixoma, began
      with symptoms of mild heart failure. Transthoracic echocardiography revealed
      recurrence of the tumor, and was therefore subjected to a second open-heart
      surgery from which she recovered without complications.

PMID- 14959454
TI  - [Ischemia-reperfusion myocardial injury].
AB  - In this article, we present some considerations on the myocardial damage due to a
      deficit of oxygen supply. In fact, this damage properly constitutes a partial
      diastolic depolarization or injury, i.e., a moderate reduction of the rest
      transmembrane potential. This phenomenon is characteristic of the acute phase of
      the myocardial infarction syndrome and is responsible for the main electrical
      manifestations appearing in this phase: disorders of rhythm and conduction, as
      well as a reduced contractility of the involved myocardial fibers. All the
      mentioned phenomena are due to a defect of the myocardial energetic mechanisms,
      owing to the mitochondrial alterations in myocytes: early reduction of the
      nicotinamide adenine nucleotides, accumulation of calcium ("calcium overload")
      into mitochondria, and a drop in oxidative phosphorylation. These changes can
      present again, more exaggerated, in a following phase of evolution of the
      myocardial infarction due to myocardial reperfusion. Its severity is related to
      the duration of the initial ischemia period. Moreover, consequences of the
      oxidative stress can add producing cellular damage by liberation of reactive
      oxygen species. Oxidant stress causes also alterations in the mitochondrial DNA,
      i.e., mutations due to oxidation of nitrogenous bases. During the initial
      ischemia phase, as well as during reperfusion, metabolic therapy can be very
      useful as, for example, glucose-insulin-potassium solutions (G-I-K). These could
      act as scavengers of the free radicals derived from oxygen and avoid or reduce
      the myocardial damage due to reperfused myocytes. Metabolic drugs, as for example
      trimetazidine, antioxidants, etc, can also be used in the myocardial reperfusion
      phase.

PMID- 14959455
TI  - [Does diastolic heart failure exist?].
AB  - This paper reviews the concepts of systolic function, diastolic function, heart
      failure, diastolic dysfunction, and diastolic heart failure. We refer to the
      historic evolution of the concept of heart failure and the origin of the term
      diastolic heart failure. Based on the current concepts of the physiology of the
      heart and its pathophysiology, we discuss the inappropriateness of the term and
      to the confusion it has generated in clinical practice, treatment, and prognosis,
      as well as in numerous research papers (of which some examples are given) when
      terming as "heart failure" the diastolic dysfunction and using both terms
      indistinctively. We conclude that an increasing need has arisen, ever more
      imperative, to identify clearly the concepts of heart failure and diastolic
      dysfunction, emphasizing on their differences to recognize them as distinct
      clinical entities with their own personality and, hence, having different
      prognosis and treatment. This would be of great help to achieve more accuracy in
      the clinical guidelines, standards, and consensus, especially regarding
      treatment. Besides it would be useful to avoid, inconsistencies in the design of
      research, which appear in some of the publications just by the lack of a clear
      meaning of the terms. Finally, at present we have the necessary elements to
      conclude that the terms "diastolic heart failure" and "cardiac failure with
      preserved systolic function" are inexact, poorly gauged, and far away from the
      actual problem they try to define. Therefore, they should be substituted by the
      concept of Diastolic Dysfunction, which defines clearly the pathophysiology of
      the functional alteration, without having to state that "the heart is failing".

PMID- 14959456
TI  - [Evaluation of myocardial perfusion with positron emission tomography (PET) with
      13N-ammonia: initial experience in Mexico].

PMID- 14959457
TI  - [National Registry of Percutaneous Coronary Interventions (RNICP)].

PMID- 14959458
TI  - [Prize of the Astronautics International Academy].

PMID- 14959459
TI  - [Topical problems of interdisciplinary cooperation in the treatment of
      psychosomatic disorders].

PMID- 14959460
TI  - [Alcohol consumption and its connection with mortality from cardiovascular
      diseases in 40-59 years old men (data from 21.5 year prospective study)].
AB  - AIM: To study contribution of alcohol consumption (AC) to mortality of coronary
      heart disease (CHD), cerebral stroke (CS), cardiovascular diseases (CVD), overall
      mortality (OM) in a random population of working males. MATERIAL AND METHODS: The
      results are available of a 21.5 year cohort study of mortality in a random
      population of 7,815 male citizens of Moscow and St-Petersburg aged 40-59 years.
      RESULTS: The attributive risk of AC for mortality of CHD, CS, CVD and OM was
      16.6, 14.8, 7.7 and 11.9%, respectively. The lowest relative risk to die of CHD,
      CVD and OM among the cohort studied was observed in males taking alcohol 168.0 ml
      per week maximum. CONCLUSION: It is necessary to approach differentially to
      assessment of AC effects on development of many diseases and further
      investigations are needed to reveal fine mechanisms of action of different
      alcohol drinks on human organism.

PMID- 14959461
TI  - [State of the left heart ventricle and 24-hour arterial blood pressure profile in
      patients with angina pectoris and episodes of silent myocardial ischemia].
AB  - AIM: To study association between the state of the left ventricle (LV) of the
      heart, characteristics of a 24-h profile of arterial pressure (AP) and episodes
      of painless myocardial ischemia (PMI). MATERIAL AND METHODS: Echocardiography,
      bifurcation 24-h monitoring of AP and ECG were conducted in 137 patients with
      effort angina (EA) receiving clinically effective antianginal therapy. RESULTS:
      Episodes of PMI at daytime were detected in 33 (24.1%) patients, at day and
      nighttime in 10 (7.3%) patients. There were significant differences neither by LV
      state nor by 24-h AP profile in patients free of PMI and those with daytime
      episodes. Patients with day and night PMI episodes had dilated LV and a decreased
      fall of night AP. Comparison of the parameters of 24-h AP and ECG monitoring has
      demonstrated that PMI episodes follow a rise in systolic and diastolic AP. In
      ischemia systolic and diastolic AP rise. In postischemic period systolic AP
      lowered while diastolic AP rose higher. CONCLUSION: Changes in diastolic AP may
      contribute to both onset and arrest of PMI. Decreased night fall in AP is one of
      the mechanisms compensating impaired coronary circulation.

PMID- 14959462
TI  - [The phenomenon of intermittent myocardial ischemia and characteristics of
      myocardial reserve in patients with myocardial infarction].
AB  - AIM: To study coronary and myocardial reserves in myocardial infarction survivors
      (MIS) with consideration of development of intermittent ischemia during
      transesophageal pacing (TEP). MATERIAL AND METHODS: 320 MIS were examined 1.5-2
      months after myocardial infarction onset. 30 healthy male volunteers served
      control. Stepwise overdrive TEP was made in all the examinees with parallel
      estimation of central hemodynamics by tetrapolar chest rheography with assessment
      of systolic and diastolic parameters. RESULTS: In the course of TEP, 39.4% MIS
      developed intermittent ischemia (II) at frequencies 120-140 imp/min. II presented
      as a significantly depressed ST segment on ECG. There was a simultaneous
      lengthening (1.4-fold) of diastole and a fall (1.5-fold) of end-diastolic
      pressure in the left ventricle (EDP). At frequencies 140-160 imp/min the length
      of the diastole shortened while EDP rose. CONCLUSION: The II phenomenon
      demonstrates a key role of coronary reserve. Changes in coronary and myocardial
      reserves during TEP in II development are interrelated. They may represent
      unknown adaptive mechanisms of the myocardium protecting against unfavourable
      outcomes of ischemic episodes.

PMID- 14959463
TI  - [Effect of membrane-stabilizing magnetolaser therapy on cardiodynamics in
      patients with ischemic heart disease].
AB  - AIM: To evaluate cardiodynamic changes in response to magnetolaser therapy (MLT)
      and these changes links with lipid shifts in cell membrane. MATERIAL AND METHODS:
      The study enrolled 50 patients with effort angina (functional class II-III). Of
      them, 37 patients were exposed to 10-day courses of MLT, 13 patients were exposed
      to sham procedures. Before the treatment and 3 months after it measurements were
      made of lipid peroxidation (LPO) products, structure of erythrocytic membrane and
      cardiodynamic parameters. RESULTS: MLT resulted in a significant reduction of LPO
      products, stabilization of cell membrane structure and positive shifts in
      cardiodynamics. Correlation was found between the above parameters. CONCLUSION:
      Improvement of inotropic, diastolic functions of the myocardium and abatement of
      cardiac remodeling in coronary heart disease patients in response to MLT is
      realized primarily due to structural stabilization of cell membrane lipid
      biolayer.

PMID- 14959464
TI  - [Effect of combined application of nitrogen baths and 6 month physical training
      on physical work capacity and extrasystole in patients with ischemic heart
      disease and stable stenocardia].
AB  - AIM: To study effects of combined use of general artificial nitric baths and
      bicycle exercise for 6 months on physical performance (PP) and extrasystole (ES)
      in patients with coronary heart disease (CHD) and stable angina pectoris (SAP) of
      functional class I-II. MATERIAL AND METHODS: A total of 129 CHD with SAP patients
      entered the study. Of them, 44 patients received balneotherapy (a course of
      general artificial nitric baths); 37 patients took the baths and exercised on
      bicycle ergometer; 48 patients took the baths, exercised on bicycle ergometer in
      the outpatient clinic and continued the exercises for 6 months. The patients were
      examined with spiroveloergometry and ambulatory Holter ECG monitoring. RESULTS:
      The latter group of patients achieved the highest training effect manifesting
      with increased PP and coronary heart reserve, an antiarrhythmic effect (a 73.3%
      fall in the mean number of ventricular ES for 24 hours, a 72.2% one in this
      number of supraventricular ES). CONCLUSION: A significant efficacy is shown of
      combined use of general nitric baths and bicycle exercise with prolongation for 6
      months in CHD patients and SAP of functional class I-II with ES.

PMID- 14959465
TI  - [Early clinical results of balloon coronary angioplasty in patients with ischemic
      heart disease and three impaired coronary vessels].
AB  - AIM: To study a short-term clinical effect of balloon coronary angioplasty (BCA)
      in patients with affection of three coronary arteries regarding an anginal form
      and completeness of myocardial revascularization. MATERIAL AND METHODS: The study
      included 80 patients with coronary heart disease (CHD) having three affected
      major coronary arteries after BCA among them 48 patients with stable and 32
      patients with unstable angina. The procedures were made using "Polydiagnost C"
      angiographic complex (Philips, Holland). RESULTS: Overall clinical efficacy of
      BCA in affection of three coronary arteries was 88.75% (in 71 of 80 patients), no
      response was observed in 9 of 80 patients (11.25%). The response to BCA was
      independent of the anginal form. In stable angina there were no differences in
      clinical efficacy in complete and incomplete functionally-adequate anatomic BCA
      (91 and 89.6%, respectively). In incomplete anatomic revascularization clinical
      effect was less (62.5%). In unstable angina a clinical effect of BCA did not
      depend on the degree of myocardial revascularization. Stenting raised clinical
      response to BCA in all the patients. CONCLUSION: The findings demonstrate high
      clinical efficacy of BCA in affection of three coronary arteries irrespective of
      an angina form. Incomplete anatomic revascularization in stable effort angina is
      less effective but can be used if other operations are impossible. If definition
      of the symptom-causing artery is possible, the intervention should be limited to
      BCA of this artery to decide on dilation of other arteries later.

PMID- 14959466
TI  - [Cerebral perfusion in patients with arterial hypertension and chronic forms of
      brain vascular pathology].
AB  - AIM: To examine cerebral perfusion in patients with dyscirculatory encephalopathy
      and residual disorders of cerebral circulation in arterial hypertension. MATERIAL
      AND METHODS: Duplex scanning of extra- and intracranial arteries, computed
      tomography of the head were performed in 26 hypertensive patients with chronic
      vascular pathology of the brain. Cerebral perfusion was studied by the evidence
      obtained at single-photon emission computed tomography. RESULTS: Impaired
      segmental perfusion of the brain, primarily of frontal and temporal location, was
      detected in 88.5% patients. Occlusive lesions of extra- and intracranial arteries
      were accompanied by significant deterioration of the perfusion while
      visualization of leukoaraosis was associated with high perfusion in the anterior
      frontal compartments indirectly pointing to defects in autoregulation of cerebral
      circulation. It was found that different correlations exist between perfusion of
      various segments of the brain and systemic arterial pressure. This is explained
      by functional and hemodynamic heterogenicity of different brain regions.
      CONCLUSION: Specific features of cerebral perfusion in patients with chronic
      forms of vascular brain pathology should be considered in planning
      antihypertensive therapy because of the risk of focal hypoxia and even ischemia
      in an inadequate fall of arterial pressure.

PMID- 14959467
TI  - [Venous dysfunction in patients with hypertension and different hemodynamic
      variants of disease].
AB  - AIM: To identify variants of venous dysfunction in patients with arterial
      hypertension (AH) in respect of the disease hemodynamic profile. MATERIAL AND
      METHODS: The assessment of central hemodynamics and peripheral venous circulation
      in the veins of the lower limbs was made in 60 patients with different
      hemodynamic variants of primary AH. RESULTS: Patients with ejection hypertension
      were characterized by high extensibility of the peripheral veins and low
      tolerance to orthostatic loads. In patients with hypertension of resistance
      venous dysfunction was characterized by signs of venous hypertension in rigidity
      of the venous wall as well as low and inadequate reactivity of peripheral large
      vessels. CONCLUSION: The results of the orthostatic test show different response
      of venous hemodynamics in patients with hypertension of ejection and resistance.
      This provides adequate activity of the heart in erect position.

PMID- 14959468
TI  - [Assessment of the efficacy and tolerance of delayed-action nifedipine as the
      monotherapy or in combination with metoprolol in patients with arterial
      hypertension].
AB  - AIM: To compare efficacy and safety of nifedipin-retard (cordaflex-retard, Egis,
      Hungary) used in monotherapy and in combination with metoprolol (egilok, Egis,
      Hungary) in patients with arterial hypertension (AH). MATERIAL AND METHODS: The
      study included 20 patients with AH stage I-II (12 males, 8 females, mean age 57.3
      years, mean duration of the disease 8.6 years). Nifedipin-retard was given in a
      daily dose 40 mg/day (20 mg twice a day) in monotherapy and 20 mg/day in
      combination with metoprolol which was administered 50 mg twice a day (a daily
      dose 100 mg/day). The control examination consisted of a physical examination,
      measurement of arterial pressure (AP) by Korotkov, registration of heart rate,
      ECG, 24-h AP monitoring, echocardiography. RESULTS: By 24-h AP monitoring, a 4
      week treatment with nifedipin-retard alone resulted in lowering of systolic
      arterial pressure. The combined treatment produced a more pronounced fall both in
      systolic and diastolic pressure. Diastolic left-ventricular function improved in
      combined therapy. Side effects observed in nifedipin-retard monotherapy got much
      more weaker when this drug combined with metoprolol. CONCLUSION: Combination of
      nifedipin-retard with metoprolol provides better clinical response and tolerance
      than monotherapy with nifedipin-retard.

PMID- 14959469
TI  - [Use of enalapril in the preparation of patients with arterial hypertension to
      the surgical procedures].
AB  - AIM: To study efficacy of enalapril, ACE inhibitor, in preparation to surgery of
      hypertensive patients with concomitant surgical diseases. MATERIAL AND METHODS:
      An open controlled randomised study of the action of enalapril preoperative
      therapy on hemodynamics was made in 55 hypertensive patients aged 36-68 years
      with surgical abdominal diseases. RESULTS: Before surgery, the study group of 30
      patients were given enalapril for a month. The control group of 24 patients
      received a month therapy with adelphan and papasol. The study group achieved a
      greater fall in the morning and evening systolic arterial pressure and morning
      diastolic pressure. These falls allowed elective operative interventions.
      Intraoperative hyperdynamic reactions, cardiac arrhythmia, intraoperative
      myocardial ischemia occurred less frequently in the study group. Enalapril
      provided better intraoperative peripheral blood saturation with oxygen.
      CONCLUSION: Enalapril, an ACE inhibitor, can be used as a hypotensive drug for
      preparation of hypertensive patients for elective surgery because it regulates
      processes providing effective stabilization of arterial pressure, adequate supply
      of oxygen to peripheral blood.

PMID- 14959470
TI  - [Efficacy, safety, and pharmaco-economical aspects of the therapy for
      dyslipidemia with brand-name and generic statins].
AB  - AIM: To compare clinical, cost-effect efficacies and safety of simvastatin Zokor
      and generic Vasilip in correction of dislipoproteinemia in patients with ischemic
      heart disease. MATERIAL AND METHODS: The original statin Zokor and generic statin
      Vasilip were given for 8 weeks in a dose 20 mg/day. RESULTS: Vasilip and Zokor
      demonstrated similar hypolipidemic efficacy and safety, but Vasilip
      administration was more cost-effective. CONCLUSION: Simvastatin Vasilip is
      recommended for wider use in clinical practice because it is clinically and cost
      effective.

PMID- 14959471
TI  - [Physical rehabilitation in the complex hospital therapy of patients with chronic
      low cardiac output].
AB  - AIM: To study action of medication in combination with free-choice bicycle
      exercise on cerebral and peripheral hemodynamics in patients with chronic heart
      failure (CHF) of functional class II-III. MATERIAL AND METHODS: At admission to
      hospital and at discharge 100 patients with CHF of NYHA functional class (FC) II
      III hospitalized for progression of CHF have undergone clinical examination,
      Doppler echocardiography and biomicroscopy of conjunctival vessels. The patients
      were randomized into two groups: group 1 of 60 patients received standard drugs
      and exercised on bicycle: group 2 of 40 patients received standard drugs only.
      RESULTS: The patients of group 2 achieved better hemodynamic effect, greater
      lowering of total peripheral vascular resistance. In patients with CHF FC II
      cardiac output increased due to improvement of left ventricular systolic function
      (end-systolic and end-diastolic volumes reduced by 20.3 and 38.7%, respectively,
      ejection fraction increased by 13.7%); in patients with FC III--due to
      improvement of diastolic function (end-diastolic volume reduced by 8.3%). Bicycle
      exercise in combined treatment of FC II CHF provides improvement in perivascular
      and intravascular components of microcirculation by 46.7 and 24.3%, respectively.
      In FC III CHF intravascular microcirculation improved by 24.3%. CONCLUSION:
      Bicycle exercise of patients with CHF of FC II and III used as an adjuvant to
      standard drugs has an additional positive effect on central hemodynamics and
      microcirculation.

PMID- 14959472
TI  - [Prolongation of the Q-T interval while taking isoniazid].

PMID- 14959473
TI  - [Dorsopathia in the practice of a therapist--new possibilities of the treatment].

PMID- 14959474
TI  - [Hypokalemia].

PMID- 14959475
TI  - [Diagnostic and prognostic value of D-dimer in the clinic of internal diseases].

PMID- 14959476
TI  - [Tiotropium bromide in the treatment of chronic obstructive lung disease].

PMID- 14959477
TI  - [Role of angiotensin-converting enzyme gene polymorphism in the development of
      metabolic syndrome].

PMID- 14959478
TI  - [Liver insufficiency: modern problems of the treatment].

PMID- 14959479
TI  - [Microalbuminuria: clinical and prognostical value in arterial hypertension].

PMID- 14959480
TI  - [Autoimmune thyroiditis in hematologic diseases].

PMID- 14959481
TI  - [Increase in duration of paradoxical sleep after carotid occlusion in rats].
AB  - Nonlinear rats, which survived after occlusion of one or two common carotid
      arteries (N = 30, about 30% survived) were examined. Sham-operated animals formed
      a control group. In animals with ischemia, the total sleep duration in a three
      hour period was substantially increased as compared to control group at the
      expense of a substantial growth (8-9 times) of paradoxical sleep (PS) phase. In
      the animals with ischemia, a sharp increase in PS was observed on the first
      postoperation day, and then PS gradually decreased from the first to the fortieth
      days. The results suggest the PS involvement in the brain intrinsic reparation
      functions.

PMID- 14959482
TI  - [Motor learning with the minimal involvement of visual afferentation].
AB  - Amongst motor control and learning models, "A Cerebellar Model of Timing and
      Prediction" of A. Barto and J. Houk is the most interesting and physiologically
      well-grounded. Developing D. Marr's "The Theory of Cerebellar Cortex", this model
      proposed the important role in motor learning of the ability of Purkinje cells to
      change their activity level by the dendritic bistability mechanism. The aim of
      this investigation was to verify this idea in experiments with human learning of
      precise elbow flexion. The unsupervisual method of learning was used in order to
      guarantee the principal role of proprioception in training. The experiments were
      carried out in darkness to exclude the vision control. Subjects were asked to
      perform a precise horizontal elbow flexion as fast as possible and repeat this
      action from 30 to 50 times up to the point of complete movement acquisition
      (stable movement with the error in the range of 5% of a given flexion amplitude).
      The target point (a given angle of the horizontal elbow flexion) was not
      presented to the subjects in advance. Reaching the target point was indicated by
      a short light flash. During training, subjects learned to hit target point with
      the given precision. Kinematic characteristics of the movement (time change of
      elbow flexion angle, velocity, and acceleration) together with EMG of the flexor
      and extensor were recorded. The obtained results were in good agreement with J.
      Houk and A. Barto's hypothesis. Analysis of changes in the kinematic
      characteristics in the course of training revealed an asymmetric velocity profile
      and a fragmentary shape of acceleration profile at the beginning of learning. In
      the course of training, the acceleration profile transformed into biphasic curve
      with a single change in polarity. Thus, it acquired a characteristic shape of a
      plateau. Correspondingly, to the end of training, the character of the asymmetry
      of the velocity profile changed. No correlation was observed between the velocity
      parameters and movement precision. These features essentially distinguish the
      motor reactions under study from the common visuomotor coordinations. It is
      suggested that the amplitude and duration of the acceleration plateau reflect the
      intensity and time of inhibition of the descending activity of Purkinje cells as
      a result of bistability (in accordance with Houk and Barto's hypothesis).

PMID- 14959483
TI  - [Development of examination stress in subjects with various levels of cortical
      activation].
AB  - The work is aimed at the study of neurophysiological mechanisms of examination
      stress in subjects with different levels of cortical activation. Spectral power
      and typical cortical connections of EEG rhythms were studied in students under
      conditions of stress before and immediately after examination as well as during
      usual academic semester. Students with relatively higher and relatively lower
      baseline alpha rhythm, i.e., with different levels of cortical activation
      revealed both similar and different EEG reactions. Before examination, in both
      groups of subjects the spectral power of EEG activity in the delta and thetal
      bands increased, and the number of connections in the bands of the alpha and beta
      1 rhythms decreased as compared to usual baseline conditions. However, the EEG
      reactions in the theta 2 band in the two groups were oppositely directed.
      Significant changes in the beta 2 power were observed only in the group of
      subjects with higher baseline level of cortical activation.

PMID- 14959484
TI  - [EEG coherence during unconscious visual set under conditions of increased
      motivation of subjects].
AB  - Prestimulus EEG was recorded in the state of "operative rest" after the
      instruction and at the stages of formation, actualization, and extinction of
      unconscious visual set to perception of unequal circles. Two motivation
      conditions were used: (1) subjects were promised to be rewarded with a small
      money price for each correct response (a "general" rise of motivation) and (2)
      only correct assessments of stimuli of a certain kind were rewarded (a
      "selective" rise of motivation). In both conditions, additional motivation of
      subjects to the results of their performance led to an increase in EEG coherence
      most pronounced in the theta and alpha 1 frequency ranges in the left temporal
      area of the cortex. During the "general" rise of motivation the EEG coherence (as
      compared to the control group) was higher in a greater number of derivation pairs
      than during the "selective" rise. EEG coherence in "motivated" subjects was
      increased already at the stage of operative rest. Later on, at the set stages, no
      significant changes were revealed. Thus, the realized set formed by the verbal
      instruction, which increased motivation of subjects to the results of their
      performance, produced substantially more prominent changes in coherence of
      cortical potentials than the unconscious set formed during perception of visual
      stimuli.

PMID- 14959485
TI  - [Changes in spectral coherent characteristics of EEG in the early postpartum
      period in mothers with anxious and depressed mood].
AB  - Postpartum EEG spectral and coherence characteristics were estimated in mothers
      with or without postpartum depressions. In mothers without affective disorders
      the power of oscillations in the delta, theta, and alpha 1 frequency bands was
      increased as compared to controls. Intrahemispheric EEG coherence between the
      left frontal and adjacent derivations in the delta and theta bands and
      interhemispheric coherence in the central areas was increased and decreased over
      the remaining cortical surface. These changes led to a significant decrease in
      EEG asymmetry. It is suggested that during normal postpartum the influence of the
      limbicodiencephalic and lower brainstem structures on the cortex is augmented and
      a certain kind of dominanta is formed. In mothers with postpartum depressions the
      EEG alpha-band power was lower than in the control and normal groups, coherence
      changes in the delta and theta bands diminished the EEG asymmetry. The
      insufficiency of limbicodiencephalic influence and impairment of adaptive
      brainstem reactions are suggested to be responsible for problems in the formation
      of maternal dominanta, which results in the development of postpartum
      depressions.

PMID- 14959486
TI  - [Dynamics of tuning to orientation of cross-like figures in neurons from the cat
      visual cortex].
AB  - Dynamics of tuning to orientation of flashing light bar and to orientation of
      cross-like figure was studied by a temporal slices method in 87 neurons of the
      cat primary visual cortex. Tuning was plotted by spikes number in the entire
      response and in its successive fragments with a step of 20 ms. It was found that
      successive dynamic shift of preferred orientation of a bar was typical for 87%
      units, white such shift of preferred orientation of a cross was met in 75% of
      cases. Comparison of tuning dynamics for bar and cross allowed to separate units
      into three groups: the first one (58.6% of cases) with larger dynamic shift of a
      bar preferred orientation then of a cross (74.9 +/- 5.8 degrees [symbol: see
      text] 29.8 +/- 4.1 degrees, correspondingly, p < 0.00001), the second group
      (21.5%) with opposite effect (24.2 +/- 5.2 degrees and 69.2 +/- 10.0 degrees, p <
      0.0002) and the third group (19.8%) without significant shift of preferred
      orientation of bar and cross and without difference in their dynamics. Possible
      mechanisms of the preferred orientation dynamics and its difference for bar and
      cross are discussed.

PMID- 14959487
TI  - [Behavioral and physiological characteristics of nonagouti mutation in gray rats
      during selection for aggressiveness].
AB  - The goal of this work was to find out to which degree the black coat color
      mutation nonagouti that appears in wild Norway rat in the course of breeding for
      the maintenance and enhancement of aggressiveness towards a human affects
      selected and other behavioral traits as well as stress reactivity and brain
      neurochemistry. Nonagouti rats displayed increased emotionality in the open-field
      and forced-swimming tests as compared to agouti animals, whereas there were no
      differences in anxiety estimated in the elevated plus-maze. Neither were there
      any differences in glucocorticoid reactions to a combined stressful procedure
      such as forced swimming. The dopamine content in the frontal cortex and striatum
      and noradrenaline content in the frontal cortex were increased in black rats as
      compared to gray rats. The result suggest that the nonagouti mutation in gray
      aggressive rats enhances the effects of selection for aggressiveness on some
      behavioral traits and brain catecholamine level.

PMID- 14959488
TI  - [Typological features of behavior and memory in Norway rats selected for absence
      of aggression toward a man].
AB  - Features of behavior and retrieval of passive conditioned avoidance on a new and
      forgotten stimuli were compared in Wistar rats and Norway rats bred for the
      absence of aggression toward a man. As distinct from white rats, grey rats were
      characterized by low anxiety and high locomotor exploratory activity in the
      elevated plus maze and dark-light chamber. Norway rats demonstrated better
      avoidance performance with active defensive behavioral strategy than Wistar rats.
      Latent inhibition during conditioning with a previously forgotten situational
      stimulus was the same in both rat strains. The results are discussed in terms of
      the use of grey rats as a model for an in-depth analysis of the mechanisms of
      memory optimization.

PMID- 14959489
TI  - [Rat behavior in a light/dark chamber: place preference task].
AB  - After a 6-week social isolation (from 22nd to 70th day from birth) male Wistar
      rats (a sibship, 10 animals), were tested for 20 min in a light/dark box in order
      to reveal behavioral features of choice of their spatial localization in unknown
      conditions. Socially deprived rats significantly differed from control animals in
      longer time of the room choice, higher number of entries of the light section,
      and higher number of rearings, which was probably explained by their higher
      anxiety and lack of experience to estimate unexpected stimuli and select a
      response. The mean level of behavioral activity during exploration of the box
      defined by the number of elementary operations per minute remained constant and
      was significantly higher in the socially deprived rats than in the control
      animals.

PMID- 14959490
TI  - [Sensory responses of neurons in the medial septal area to modulation of the
      theta-activity by alpha2-adrenergic receptor agonist clonidine].
AB  - It was shown by us earlier that bilateral intracerebroventricular injection of
      alpha2-adrenoreceptor agonist clonidine produced a dose-dependent effect on theta
      oscillations in the septohippocampal system of awake rabbits. A relatively low
      dose of clonidine (0.5 microgram) attenuated and a high dose (5 micrograms)
      significantly enhanced the rhythmic activity. It was suggested that the effect of
      the low dose of clonidine is mediated by presynaptic alpha2-adrenoreceptors were
      as postsynaptic alpha2-adrenoreceptors. In this article sensory neuronal
      responses in the medial septal area (MS) were analyzed against the background of
      the theta activity modulation by different clonidine doses. Different effects of
      the low and high doses of the agonist were revealed. The low dose of clonidine
      (0.5 microgram in 5 microliters into each lateral ventricle) which produced a
      decrease in the theta activity resulted in attenuation of excitation and
      enhancement of inhibition, i.e., the number of activating effects significantly
      decreased and inhibitory responses were more frequent and distinct. The high dose
      of clonidine (5 micrograms in 5 microliters) which produced a sharp increase in
      the theta activity led to a significant decrease in the reactions of the MS cells
      to sensory stimuli (from 76.8% in the control to 45% under clonidine)
      independently on the initial reaction character. Persisted excitatory and
      inhibitory responses became less distinct than the initial ones except single
      excitatory reactions. The results suggest that alpha2-adrenoreceptors are
      involved in the control of the sensory reactivity of MS neurons. A sharp decrease
      in neuronal reactivity during stable rhythmical oscillations developing under the
      influence of high dose of clonidine confirm the role of the theta rhythm in the
      septohippocampal system as an active filter in information selection and
      registration.

PMID- 14959491
TI  - [Selective involvement of opioids in mechanisms of synapse-specific plasticity in
      Helix lucorum snail during sensitization acquisition].
AB  - Effects of met-enkephalin (opioid peptide) and naloxone (opioid antagonist) on
      nociceptive sensitization were studied in L-RP11 Helix neurons. In control snails
      sensitizing stimulation produced reversible membrane depolarization and
      depression of neural responses evoked by sensory stimuli during the short-term
      stage of sensitization and facilitation of these responses at the long-term
      stage. Met-enkephalin (10 but not 0.1 microM) suppressed the neural responses
      evoked by nociceptive stimuli. Sensitizing stimulation during metenkephalin
      application prevented the facilitation of neural responses evoked by tactile
      stimulation of snail head, whereas facilitation of neural responses evoked by
      chemical stimulation of head or tactile stimulation of foot were similar to that
      in control sensitized snails. Sensitizing stimulation during met-enkephalin
      and/or naloxone application prevented the facilitation of neural responses evoked
      by chemical stimulation of snail head, whereas responses evoked by tactile
      stimulation of snail head or foot were facilitated (as in neurons of control
      sensitized snails). Opioids are suggested to be involved in regulation of
      nociceptive mechanisms and selective induction of long-term plasticity in L-RP11
      neural inputs activated by tactile of chemical stimulation of snail head.

PMID- 14959492
TI  - [Effect of weak electromagnetic radiation on learning in the grain beetle
      Tenebrio monitor].
AB  - Weak electromagnetic radiation (36 GHz, 100 MicroW/cm2) was used to study its
      effect on learning and memory of larvae and imago of the grain beetle Tenebrio
      molitor. The insects were learned to choose the direction in a T-maze. The
      retention was tested a month later. They were exposed to weak electromagnetic
      radiation before or after the learning experiments. Previous exposure to weak
      electromagnetic radiation stimulated learning of both larvae and imago. The
      effect depended on the developmental stage of the larvae. It was considerably
      stronger in larvae exposed to weak electromagnetic radiation immediately after
      their molting. It was better in the first half of the instar than in the second
      half. It is suggested that the effect of weak electromagnetic radiation can
      correlate with the function of hormones of metamorphosis.

PMID- 14959493
TI  - [Maternal glucocorticoid hormones as a factor mediating the effect of prenatal
      stress on offspring anxiety].
AB  - The plus-maze behavior was studied in offsprings of female rats subjected to
      immobilization stress on the 15-18 days of pregnancy. Prenatal stress decreased
      the level of anxiety in males and increased in females. The blockade of the
      mother's stress-induced glucocorticoid secretion by prior adrenalectomy and
      subsequent corticosterone injection during immobilization in a low dose (0.3
      mg/kg) prevented the behavioral disorders in offsprings. In case of a higher dose
      of corticosterone (3 mg/kg) injection, the behavior of offsprings was the same as
      that of offsprings of the intact mothers subjected to immobilization. The results
      suggest that the stress-induced increase in maternal glucocorticoid level may be
      the mechanism by which prenatal stress impairs the development of sex differences
      in rat anxiety behavior.

PMID- 14959494
TI  - Effect of vibrissae removal on search accuracy in the water maze.
AB  - In two experiments the vibrissae were clipped on either the left, the right or
      both sides, and the rats were trained to find a submerged platform in the Morris
      water maze. In both experiments, animals without vibrissae on both sides or on
      the left consistently spent significantly more time in the 'counter' area twice
      the platform diameter in size, surrounding the submerged platform, than intact
      controls. Counter preference was not as consistent across experiments in rats
      with right vibrissae removed. These results suggest that the vibrissae are
      required for proprioceptive location of the platform itself, but not for proximal
      search accuracy. Since ischaemic damage to hippocampal CA1 pyramidal cells has
      also been reported to prolong counter search during training, the results support
      the suggestion that impaired hippocampal processing of proprioceptive information
      from the vibrissae may contribute to the increased latency to find the platform
      shown by ischaemic rats.

PMID- 14959495
TI  - [Anxiolytic effect of dehydroepiandrosterone sulfate in male mice with high
      anxiety level].
AB  - Effects of dehydroepiandrosterone sulfate (DHEAS, 30 mg/kg, i.p., 4 and 28 hours
      after an injection) on CBA/Lac male mice with increased level of anxiety
      resulting from chronic (20-day) social confrontations were studied in two
      behavioral tests. The anxiolytic effect of DHEAS was observed both 4 and 28 hours
      after an injection in the partition test of social interactions and in the plus
      maze test.

PMID- 14959496
TI  - [Age-related changes in characteristics of evoked responses in the CA1 area of
      hippocampal slices after forelimb deafferentation].
AB  - The effect of forelimb deafferentation (median nerve transection) on postnatal
      development of hippocampal synaptic transmission was studied. Paired-pulse
      paradigm was applied to determine the properties of short-term plasticity, such
      as paired-pulse facilitation (PPT) in hippocampal slices. Significant changes in
      the time course of the PPT development were observed after the forelimb
      deafferentation. It was shown that the earlier described decrease in a population
      spike amplitude can be related not only to modification of synaptic efficacy but
      to some destructive processes, i.e., elimination of synapses and neurons. It was
      followed by the period by intensive formation of new synapses. The data suggest
      that there is no acceleration or delay in hippocampal development after the
      forelimb deafferentation but new intrahippocampal networks are formed.

PMID- 14959497
TI  - [Delayed effects of neurotensin microinjections into the substantia nigra on
      conditioned motor reactions of rats with lesions to serotoninergic neurons].
AB  - Behavioral effects of neurotensin microinjections into the brain substantia nigra
      of rats with neurotoxic (5,7-dihydroxytryptamine) lesions of serotoninergic
      neurons in the dorsal raphe nucleus were studied. It was shown that neurotensin
      facilitated extinction of conditioned and intertrial reactions to negative
      (unreinforced) stimuli, but did not change the actualization of positive (with
      water reward) conditioned signals. Neurotensin-induced effects persisted in
      subsequent experiments without injections of the peptide. Neurotensin injections
      reduced the negative emotional states of lesioned animals in the arena during
      testing conditioned preference. It was concluded that the behavioral effects of
      neurotensin can be explained by the formation in the lesioned animals of the
      situational emotional state facilitating adaptive brain functions.

PMID- 14959498
TI  - [Conditioning of gray crows (Corvus cornix L.) in a "giant" eight-arm radial
      maze].
AB  - Twelve adult hooded crows (Corvus cornix) were trained to perform a standard
      radial-maze task in a giant eight-arm outdoor radial maze constructed at the
      "Chistyi les" Biological Station (Tver oblast) for comparative investigations of
      spatial memory in birds and mammals. The maze consists of a central part of 250
      cm diameter, and has arms of 650 cm length, 170 cm height and 80 cm width. The
      examined hooded crows showed good task performance. Errors (repeated visits to
      empty arms) were few in number and were predominantly connected with the tendency
      to avoid arms close to an observer.

PMID- 14959499
TI  - Employment-based retirement and pension plan participation: declining levels and
      geographic differences.

PMID- 14959500
TI  - Experimental psychology: journal statistics and trends.

PMID- 14959501
TI  - The influence of distractor-only prime trials on the location negative priming
      mechanism.
AB  - Two experiments were conducted that examined the influence of distractor-only
      prime trials on the "location" negative priming (NP) effect. In all experiments,
      the probe trial always lacked a distractor. We showed that the predictable
      absence of a probe distractor caused the elimination of the location NP effect
      when the prime trial contained both a target and a distractor event (T + D-->T),
      but not when the prime contained only a to-be-ignored distractor event (D-->T)
      (Milliken, Tipper, Houghton, & Lupianez, 2000). The preservation of the NP effect
      seen with the distractor-only prime trials (D-->T) was not the result of its
      lacking a prime-trial selection, nor was it the consequence of its representing a
      higher level of episodic similarity than the T + D-->T condition. Finally, the
      location NP effect observed for the D-->T condition is seemingly consistent with
      the view that location NP and the inhibition-of-return effects share a common
      underlying process (Milliken et al., 2000).

PMID- 14959502
TI  - Immediate and delayed recall of visually presented sentences: evidence for the
      involvement of phonological information.
AB  - The lure intrusion effect refers to the observation that lexical priming affects
      recall of sentences. This effect is taken as evidence against the contribution of
      surface information, even with immediate sentence recall. Recently, Rummer and
      Engelkamp (2003a) demonstrated that this effect, which is usually observed under
      rapid serial visual presentation (RSVP), does not appear under immediate recall
      of auditorily presented sentences. This finding indicates that surface
      information (i.e., phonological or acoustic-sensory information) can contribute
      to immediate sentence recall. So far, however, the findings do not allow for a
      decision on whether phonological and/or acoustic-sensory information is used in
      immediate sentence recall. In order to dissociate the two kinds of surface
      information, an experiment was conducted in which immediate and delayed recall
      were tested for sentences that were visually presented for a longer period of
      time than in RSVP. This kind of presentation should support phonological
      representations, but does not allow for acoustic-sensory representations. The
      findings showed a smaller intrusion effect for immediate than for delayed recall.
      This indicates that, if available, phonological information is involved in
      immediate sentence recall thereby reducing the lure intrusion effect.
      Furthermore, the findings support the assumption that the phonological trace
      provided via RSVP reading is weaker than in normal reading.

PMID- 14959503
TI  - Perception of danger signals: the role of control.
AB  - How does the perceptual system process stimuli that signal aversive outcomes or
      dangers? Considering the functional links between perception, attention, and
      action regulation, we posit that when people can avoid the aversive consequences,
      sensitivity of the perceptual system to danger signals should be enhanced,
      whereas it should be reduced when there is no such option. To test this
      prediction, we used a search task in which tachistoscopically presented
      conjunctions of features had to be detected. Parameters of sensitivity and
      response bias were analyzed drawing on procedures from signal detection theory.
      Although the experimental procedure rewarded correct responses, the predicted
      asymmetry emerged. For stimuli that were linked to a negative consequence (loss
      of points in the experimental game), perceptual sensitivity was enhanced when
      participants had the opportunity to neutralize the loss in a second task; an
      opposite pattern emerged when they had no such opportunity.

PMID- 14959504
TI  - Acquisition and use of mental operators: the influence of natural order of
      events.
AB  - The present article reports two experiments investigating the influence of
      natural order of events on the acquisition and use of knowledge about operations,
      in short mental operators. The principle of use specificity states that task
      performance depends directly on the similarity between acquisition context and
      the present situation. In contrast, the principle of natural order proposes that
      knowledge about operations can always be applied easier (faster) if reasoning
      follows the natural order of events. In Experiment 1, participants had to apply
      alphabet-arithmetic operators and LISP functions in a prognosis task (A + 2 = ?)
      or a retrognosis task (? - 2 = A). In alphabet-arithmetic, an advantage for the
      first kind of task at the beginning of training decreased with increasing
      practice. In LISP, however, a preference for this task (corresponding with a
      prospective knowledge use) emerged with increasing practice. In Experiment 2,
      arithmetic relations between digit pairs had to be induced. In a causal context
      condition, relations were described as input and output of electric circuits, in
      a neutral context the relations were described as arithmetic dependencies. A
      preference for the prognosis task was found for the causal context condition
      (corresponding with a prospective knowledge use) but not for the neutral one. The
      findings suggest that the natural order of events moderates the acquisition and
      use of mental operators. Further research is required to clarify the bases for
      this moderation.

PMID- 14959505
TI  - Time window from visual images to visual short-term memory: consolidation or
      integration?
AB  - When two dot arrays are briefly presented, separated by a short interval of time,
      visual short-term memory of the first array is disrupted if the interval between
      arrays is shorter than 1300-1500 ms (Brockmole, Wang, & Irwin, 2002). Here we
      investigated whether such a time window was triggered by the necessity to
      integrate arrays. Using a probe task we removed the need for integration but
      retained the requirement to represent the images. We found that a long time
      window was needed for performance to reach asymptote even when integration across
      images was not required. Furthermore, such window was lengthened if subjects had
      to remember the locations of the second array, but not if they only conducted a
      visual search among it. We suggest that a temporal window is required for
      consolidation of the first array, which is vulnerable to disruption by subsequent
      images that also need to be memorized.

PMID- 14959506
TI  - Inhibition of response mode in task switching.
AB  - Task inhibition was explored in two experiments that employed a paradigm in which
      participants switched among three tasks. Two tasks required manual choice
      responses based on numerical judgment (parity or magnitude), whereas a third task
      required an unconditional double-press of both response keys. Both experiments
      showed that switching to a just-abandoned task (n-2 task repetition) generally
      leads to a performance cost relative to switching to another task. Specifically,
      this task inhibition effect also occurred for the double-press task, suggesting
      inhibition of response mode. Prolonging the task-cuing interval showed that
      advance task preparation reduced only inhibition of the double-press task but not
      of the choice tasks (Experiment 1). Prolonging the response-cue interval led to a
      decrease of the inhibition effect in all tasks (Experiment 2), suggesting a time
      based release of task inhibition. Together, the experiments support the notion of
      a response-related component of task inhibition.

PMID- 14959507
TI  - The on-line resolution of the sentence complement/relative clause ambiguity:
      evidence from Spanish.
AB  - Two self-paced reading experiments investigated syntactic ambiguity resolution in
      Spanish. The experiments examined the way in which Spanish subjects initially
      interpret sentences that are temporarily ambiguous between a sentence complement
      and a relative clause interpretation. Experiment 1 examined whether the sentence
      complement preference found in English is observed in Spanish speaking subjects.
      In Experiment 2, verbal mood was manipulated in order to study the influence of
      verb-specific information on sentence processing. Since subcategorization for a
      subjunctive complement clause is generally assumed to be a lexical property of
      some verbs, the manipulation of the mood of the embedded verb affords us an
      interesting and novel way to examine the influence of lexical information on
      syntactic ambiguity resolution. Experiment 1 showed that Spanish speakers
      initially interpret the ambiguous that-clause as a sentence complement.
      Experiment 2 showed that verb-specific information, in particular, the
      information that specificies that a verb subcategorizes for a subjunctive
      complement, is accessed and used rapidly and affects the ambiguity resolution
      process. The results are discussed in relation to current models of sentence
      processing.

PMID- 14959508
TI  - On the perceptual generality of the unit-decade compatibility effect.
AB  - Number magnitude is assumed to be holistically represented along a single mental
      number line. Recently, we have observed a unit-decade-compatibility effect which
      is inconsistent with that assumption (Nuerk, Weger, & Willmes, 2001). In two
      digit Arabic number comparison, we have demonstrated that compatible comparisons
      in which separate decade and unit comparisons lead to the same decision (32_47, 3
      < 4 and 2 < 7) were faster than incompatible trials (37_52, 3 < 5, but 7 > 2).
      Because overall distance was matched, a holistic model could not account for the
      compatibility effect. However, one could argue that the compatibility effect was
      due to the specific vertical perceptual arrangement of the two-digit numbers in
      Nuerk et al.'s (2001) experiment where the decade digits and unit digits were
      presented column-wise above each other. To examine this objection, we studied the
      perceptual generality of the compatibility effect with diagonal presentation. We
      replicated the compatibility effect with diagonal presentation. It is concluded
      that the compatibility effect is not due to encoding characteristics imposed by
      the perceptual setting of the original experiment. In particular, the assumption
      of an overall analog magnitude representation for two-digit numbers is not
      consistent with these data.

PMID- 14959509
TI  - Incidence of colorectal cancer in West Virginia from 1993-1999: an update by
      gender, age, subsite and stage.
AB  - The sensitivities of different screening methods for pre-cancerous adenomas may
      affect the apparent anatomical distribution of colorectal cancers. Our objective
      was to describe changes in the distribution of left and right-sided colon cancers
      by time while adjusting for age, gender, stage and year of diagnosis. We studied
      the 7,895 cases of colorectal cancer reported to the West Virginia Cancer
      Registry between 1993 and 1999 and termed cancers proximal to, but not including
      the sigmoid colon as "right-sided," and the remaining tumors as "left-sided."
      Multivariate analyses were used to differentiate the effects of age and gender on
      changes in tumor location over time. The impact of screening was shown by the
      increase in the percentage of localized disease from 30.5% among cancers in the
      proximal colon to 37.6% in the distal colorectum. In contrast, the percentage of
      regional disease decreased from 50% among cancers in the proximal colon to the
      distal colorectum. The male to female ratios also increased from the proximal
      colon to the distal colorectum. Incidence rates, regardless of time, increased
      with advancing age for cancers located in all anatomical subsite groups, but more
      substantially for proximal colon cancer than for descending and distal colorectal
      cancers. For males ages > 85 and for females who are > 75 years of age, the
      cancer rates arising in the proximal colon exceeded observed in groups but more
      substantially for proximal colon cancer than for descending and distal colorectal
      cancers. For males age > 85 and females > 75, the cancer rates arising in the
      proximal colon exceeded those arising in the distal colorectum. This shift
      occurred at a younger age among females than males. The apparent shift of
      colorectal cancers to more proximal locations with advancing age has important
      implications for screening strategies. A further decrease in the relative
      incidence of left-sided colon cancers may require modifying current practices to
      include more frequent use of screening colonoscopy, particularly in women ages 75
      years or older.

PMID- 14959510
TI  - Breast and ovarian cancer genetics and prevention.
AB  - Inherited breast and ovarian cancers account for 10% of all breast and ovarian
      cancers. Relative to sporadic breast and ovarian cancers, these cancers tend to
      occur at an earlier age and grow more aggressively. Women with BRCA1 and BRCA2
      mutations (BRCA1/2 mutation) have a 65% to 85% cumulative lifetime risk of
      developing invasive breast cancer and a 15% to 65% cumulative lifetime risk of
      developing invasive ovarian cancer. Identification of patients with the mutation
      is therefore crucial, because preventive measures such as prophylactic bilateral
      mastectomy, prophylactic bilateral salpingpo-oophorectomy and chemoprevention
      with Tamoxifen can prevent breast and ovarian cancer. Likewise, genetic
      counseling prior to testing is important, considering the major impact of the
      test results on an individual's life.

PMID- 14959511
TI  - Loin pain hematuria syndrome: case series.
AB  - Loin pain hematuria syndrome (LPHS) is a rare condition manifested by flank pain,
      hematuria, and occasional low-grade fevers. Usually there are no physical
      findings other than hematuria. Although numerous etiological theories exist, the
      pathophysiology of LPHS is unknown and diagnosis remains one of exclusion. Renal
      autotransplantation has been suggested as an effective procedure to control the
      severe and debilitating pain. However, pain often recurs in the long term. This
      paper reviews our experiences with the diagnosis and management of this
      condition.

PMID- 14959512
TI  - President signs historic Medicare bill with hospital relief.

PMID- 14959513
TI  - Senate to consider patient safety, BioShield in January.

PMID- 14959514
TI  - Medicare exclusion proposal should not apply to hospitals.

PMID- 14959515
TI  - Proposed PPS for psychiatric hospitals.

PMID- 14959516
TI  - We cannot fear change.

PMID- 14959517
TI  - As the dust clears.

PMID- 14959518
TI  - Vitamins. The sunshine fix.

PMID- 14959519
TI  - The mysteries of hope and healing.

PMID- 14959520
TI  - Masters of the universe. NCHL, national accrediting agency push controversial
      plan to transform how MHA programs teach future healthcare execs.
AB  - An ambitious effort by a high-profile group of healthcare executives, including
      the National Center for Healthcare Leadership's Executive Vice President and
      Chief Operating Officer Marie Sinioris, left, hopes to transform the way health
      administrators are taught by the nation's MHA programs. If they're successful, it
      could mean major changes in curriculum and job skills of healthcare executive
      candidates.

PMID- 14959521
TI  - Coverage is job one. IOM report calls for reform, universal coverage by 2010.

PMID- 14959522
TI  - GNYHA, SEIU to heal N.Y.

PMID- 14959523
TI  - The right thing to do. ACHE nails down exactly how ethics apply.

PMID- 14959524
TI  - Relief in sight. Hospital inflation expected to ease, experts say.

PMID- 14959525
TI  - Survey says. Coalition tries to alter size, course of CMS project.

PMID- 14959526
TI  - Increase intervention. W.Va. hospital challenges rival's rate request.

PMID- 14959527
TI  - Different light. Two studies question validity of volume measures.

PMID- 14959528
TI  - Play fair. Ark. AG accuses Blues of monopolizing local market.

PMID- 14959529
TI  - Winds of change. Chicago area soon may see hospital beds shoot up.

PMID- 14959530
TI  - Where to invest healthcare dollars. Diabetes an example of how spending on
      prevention can save lives, costs.

PMID- 14959531
TI  - Successful succession. Texas system's CEO keeps focus on quality, efficiency.

PMID- 14959532
TI  - A service career. Mathis to be honored for life's work.

PMID- 14959533
TI  - Brave new babies.

PMID- 14959534
TI  - No girls, please.

PMID- 14959536
TI  - One, two, three or more?

PMID- 14959535
TI  - The ancient art of making babies.

PMID- 14959537
TI  - The doctor gets a checkup.

PMID- 14959538
TI  - The price of booze.

PMID- 14959539
TI  - A view of dementia.

PMID- 14959540
TI  - Smarm and the country.

PMID- 14959541
TI  - Protein shake-up. Staking out safe entrees.

PMID- 14959542
TI  - Smallpox mixes make a stir.

PMID- 14959543
TI  - Health, right and wrong.

PMID- 14959544
TI  - What 'girls' should know.

PMID- 14959545
TI  - The good news about prions.

PMID- 14959546
TI  - Sparring for control. Providers express guarded optimism as both sides of the
      political aisle seek high ground on access issue, improvements in care.
AB  - In the wake of Medicare reform and proposals from President Bush, left, in the
      State of the Union address, healthcare is taking shape as a central issue in the
      2004 presidential campaign as Democrats and the GOP wrestle to control the issue.
      Bush's plans won mixed reviews from providers, while Sen. Edward Kennedy offered
      a more sweeping approach to extending coverage to the uninsured.

PMID- 14959547
TI  - Saving small businesses. Reports suggest AHPs may harm rather than help.

PMID- 14959548
TI  - HHS finally adds up new regs. Long-awaited HIPAA element: provider ID numbers.

PMID- 14959549
TI  - Striking back at doc investors. OhioHealth pulls hospital privileges for
      physicians in largest revocation to date.

PMID- 14959550
TI  - Growing gap. Not-for-profit downgrades top upgrades again.

PMID- 14959551
TI  - Learning on the job. Federal initiative trains hospital employees at work.

PMID- 14959552
TI  - New rules, same complaints. Web site posts gripes about work-hours violations.

PMID- 14959553
TI  - A game of concentration. Stanford pushes first-year students to select major.

PMID- 14959554
TI  - Beacon of hope. Even as estimates of fraud shoot up, experts see recovery for
      HealthSouth.

PMID- 14959555
TI  - Too much money. Pa. regulators require Blues to submit surplus info.

PMID- 14959556
TI  - Under new management. Two private equity firms acquire design, building giant
      Marshall Erdman.

PMID- 14959557
TI  - The promises and the reality. A benchmark shows real cost and effect of
      candidates' plans for the uninsured.

PMID- 14959558
TI  - Who will take charge on quality? Plethora of initiatives has providers wondering
      what to report and to whom.

PMID- 14959559
TI  - Where have all the good deals gone? '90s mergers and acquisition explosion looks
      more like an anomaly, not a trend.

PMID- 14959560
TI  - Virtual access. Despite concerns, more physicians are realizing the value of
      online medical consultations. Getting reimbursed is another story.

PMID- 14959561
TI  - Molecular bases of autosomal recessive limb-girdle muscular dystrophies.
AB  - Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetically
      determined disorders with a primary or predominant involvement of the pelvic or
      shoulder girdle musculature. The clinical course is characterized by great
      variability, ranging from severe forms with rapid onset and progression to very
      mild forms allowing affected people to have fairly normal life spans and activity
      levels. Sixteen loci have been so far identified, six autosomal dominant and ten
      autosomal recessive. Linkage analyses indicate that there is further genetic
      heterogeneity both for dominant as well as for recessive LGMD. The dominant forms
      (LGMD1) are generally milder and relatively rare, representing less than 10% of
      all LGMD. The autosomal recessive forms (LGMD2) are much more common, having a
      cumulative prevalence of 1:15,000 with a number of geographical differences. The
      product of ten autosomal recessive LGMD genes has so far been identified. They
      are: calpain-3 (LGMD2A), dysferlin (LGMD2B), alpha-sarcoglycan (LGMD2D), beta
      sarcoglycan (LGMD2E), gamma-sarcoglycan (LGMD2C), delta-sarcoglycan (LGMD2F),
      telethonin (LGMD2G), TRIM32 (LGMD2H), fukutin-related protein (LGMD2I) and titin
      (LGMD2J). There are, however, at least 25% of families who can be excluded from
      any known locus. The present review is devoted to outline the present
      advancements in the molecular bases of autosomal recessive LGMD.

PMID- 14959562
TI  - Muscle sarcopenia: an overview.
AB  - Sarcopenia is the physiological age related decline in muscle mass and strength.
      The aetiology is multifactorial involving changes in muscle metabolism, endocrine
      changes, nutritional factors and mitochondrial & genetic factors. Various
      treatment modalities have been utilized including hormone replacement therapies
      but only high resistance training (HIRT) exercise has been of significant
      benefit. Despite recent advances the exact pathogenesis and therapies are not
      well understood and need further investigation. This paper reviews the current
      knowledge of aetiopathogenesis and treatments of sarcopenia and suggests future
      strategies to enhance the understanding of muscle aging and potential therapies.

PMID- 14959563
TI  - A comparative morphological study in 33 cases of respiratory chain
      encephalomyopathies.
AB  - Mitochondrial encephalomyopathies (ME) are clinically and genetically
      heterogeneous syndromes ranging from pure myopathies to complex multisystem
      disorders. This phenotypic and genotypic variability, coupled with the lack of a
      laboratory gold standard marker for the diseases, makes diagnosis a challenging
      process. Mitochondrial DNA analysis and biochemical assay of muscle homogenates
      are quite specific diagnostically but have low sensitivity in unselected cases
      suspected of ME. We decided to evaluate four routine morphological methods in 33
      cases of definite or probable ME in an effort to assess the reliability of each
      of these techniques in diagnosing ME.

PMID- 14959564
TI  - Expression of emerin and lamins in muscle of patients with different forms of
      Emery-Dreifuss muscular dystrophy.
AB  - Emerin and lamins are nuclear proteins, which are missing or defective in Emery
      Dreifuss muscular dystrophy (EDMD). The aim of this study was to test the
      expression of these proteins in skeletal muscles in the X-linked (X-EDMD) and
      autosomal dominant (AD-EDMD) form. The study group consisted of 11 patients with
      X-EDMD, 11 patients of the AD-EDMD and 20 age-matched normal subjects. Expression
      of emerin and lamins in muscles were analyzed by Western blotting and the
      immunocytochemical technique. Using the Western blotting procedure emerin was
      detected in traces in the X-linked form. In the majority of these cases (6/11) it
      was connected with a decreased concentration of lamin A, in four patients a
      lowered concentration of lamin C was present. Lamin B2 was either normal (8/11),
      or decreased (3/11). Deficit of lamin A was a characteristic feature for AD-EDMD
      in the majority of these cases (9/11), while in two of these patients a decrease
      of lamin C, in four cases a lowered level of emerin was also present. In one AD
      EDMD patient of a decrease of lamin C, but normal lamin A was present. Following
      the immunocytochemical examination the decrease of lamin A/C in X-EDMD and of
      emerin in AD-EDMD was also observed. The above mentioned data demonstrated that
      in X-EDMD and AD-EDMD the deficit of the appropriate proteins is not restricted
      either to emerin or lamins. The defect is more widespread and results in
      disruption of several nuclear proteins. This study also indicated that for the
      diagnostic EDMD purposes the immunocytochemical detection of emerin/lamins has to
      be accomplished by quantitative immunochemical analyses of the above mentioned
      proteins.

PMID- 14959565
TI  - Distribution of extremity muscle weakness in myasthenia gravis: sparing of
      tibialis anterior muscle.
AB  - We evaluated the distribution of muscle weakness in 70 myasthenia gravis (MG)
      patients, using the MRC scale. Extensors in the upper extremities and proximal
      flexors in the lower extremities (LE) were found to be weak. Tibialis anterior
      muscle was rarely affected and only when there was substantial weakness in LE
      proximal muscles. Attention to this distribution may help in differentiating MG,
      particularly MG with only limb weakness, from muscular dystrophies.

PMID- 14959566
TI  - More disclosure of NIH scientists' private work, pay?

PMID- 14959567
TI  - Perspectives. Bush pushes catastrophic, individual coverage, med-mal caps.

PMID- 14959568
TI  - The race to contain a virus.

PMID- 14959569
TI  - The power of love.

PMID- 14959570
TI  - The chemistry of desire.

PMID- 14959571
TI  - Sexual healing.

PMID- 14959572
TI  - Animal attraction.

PMID- 14959573
TI  - The marriage savers.

PMID- 14959574
TI  - The porn factor.

PMID- 14959575
TI  - Sex talk through the ages.

PMID- 14959576
TI  - Bondage unbound.

PMID- 14959578
TI  - Risking marriage and dignity, we examine methods of ... Spicing it up.

PMID- 14959577
TI  - Still sexy after 60.

PMID- 14959579
TI  - A to Z guide.

PMID- 14959580
TI  - Stub out that butt! But don't try to go it alone. Here are some tricks that make
      it easier to quit.

PMID- 14959581
TI  - Do women need a Viagra?

PMID- 14959582
TI  - Going beyond Atkins.

PMID- 14959583
TI  - Starve your way to health.

PMID- 14959584
TI  - A simple cure for confusion.

PMID- 14959586
TI  - In a race against time.

PMID- 14959585
TI  - You will start to feel very sleepy.... ...And you should go to bed, because
      shortchanging your rest can hurt your health.

PMID- 14959587
TI  - Accepting life's limits.

PMID- 14959588
TI  - A new generation gap.

PMID- 14959589
TI  - Now, reduce your risk of Alzheimer's.

PMID- 14959590
TI  - Meat market madness. Who are the likely losers (and surprising winners) in the
      wake of the big beef scare?

PMID- 14959591
TI  - When people die alone.... ...A meditation on humanity.

PMID- 14959592
TI  - Determinants of congruence between the preferred and actual place of death for
      terminally ill cancer patients.
AB  - A prospective cohort study was conducted to explore the extent of congruence and
      to identify the determinants of congruence between the preferred and actual place
      of death of terminally ill cancer patients. A total of 180 terminally ill cancer
      patients were enrolled (87% response rate) and 127 died during the one-year study
      period. Nearly 90% of the subjects preferred to die at home. One-third achieved
      their preference for place of death. The kappa value of congruence (kappa = 0.11,
      95% confidence interval = 0.05-0.17) indicated poor to slight agreement between
      the preferred and actual place death. Important determinants of congruence
      between the preferred and actual place of death for terminally ill cancer
      patients included rehospitalisation and receiving hospice home care during the
      final days of life, perceived ability for family to help achieve preferred place
      of death, and residence in New Haven County. CONCLUSIONS: This study directly
      confirms that the degree of congruence between the preferred and actual place
      death is unsatisfactory. Clinical interventions and health policies need to be
      developed to assist terminally ill cancer patients who may not be able to achieve
      their preference for place of end-of-life care and death.

PMID- 14959593
TI  - Breaking bad news: impact of a continuing medical education workshop.
AB  - OBJECTIVE: To evaluate the impact of an interactive continuing medical education
      workshop designed to help physicians in breaking bad news to their patients.
      METHODOLOGY: Analysis of post-workshop questionnaires from 539 physicians
      assessing the retention of the key concepts and the perception of the potential
      impact of the workshop on their practice immediately after the workshop and six
      months later. RESULTS: The most significant concepts retained by the respondents
      are: the need to take into consideration the whole patient (42.7% post-workshop
      and 45.6% of follow-up responses), the need to be prepared for the consultation
      (11.6% and 15%), the importance of better guiding the interview (18.8% and
      13.6%), and the value of taking more time during the consultation (5.8% and
      8.3%). Analysis of paired responses on the post-workshop and the follow-up
      questionnaires shows that 35% of the concepts retained are identical. CONCLUSION:
      The majority of physicians retained the key concepts, both immediately following
      the workshop and in the longer term.

PMID- 14959594
TI  - How do physicians learn to provide palliative care?
AB  - Medical interns, residents, and fellows are heavily involved in caring for dying
      patients and interacting with their families. Due to a lack of formal medical
      education in the area, these house staff often have a limited knowledge of
      palliative care. The purpose of this study was to determine how, given inadequate
      formal education, house staff learn to provide palliative care. Specifically,
      this study sought to explore the extent to which physicians learn to provide
      palliative care through formal medical education, from physicians and other
      hospital staff, and by on-the-job learning. Twenty physicians were interviewed
      about their medical education and other learning experiences in palliative care.
      ATLAS/ti software was used for data coding and analysis. Analysis of transcripts
      indicated that house staff learn little to nothing through formal education, to
      varying degrees from attending physicians and hospital staff, and mostly on the
      job and by making mistakes.

PMID- 14959595
TI  - Factors associated with palliative care knowledge among internal medicine house
      staff.
AB  - PURPOSE: To assess knowledge and associated factors in palliative care. METHODS:
      Self-administered survey of 88 internal medicine house officers in 1996. RESULTS:
      Twenty-one interns and 36 residents completed the survey for a response rate of
      65%. Most house officers reported 1-5 hours of prior formal training in
      palliative care, 1-5 hours in pain management, and 6-20 hours in ethics. The mean
      knowledge score was 75% correct (SD = 8); pain management scores were lowest
      (70%). Overall, interns had a significantly lower mean score than residents (70%
      vs. 77%; p = 0.001). In multivariate analysis, only the year of residency was
      significantly associated with knowledge score; prior formal training in
      palliative care, pain management, or ethics was not. One third of house officers
      rated themselves as "not at all" or "only slightly" at ease in caring for a dying
      patient. These self-ratings were not associated with prior training or knowledge,
      but were higher in residents compared to interns. CONCLUSIONS: Palliative care
      knowledge and ease with dying patients were higher in later years of residency
      but were not associated with prior formal palliative care training. These data
      highlight the continued need to evaluate and improve training in palliative care
      and pain management.

PMID- 14959596
TI  - Pain relief with short-term irradiation in locally advanced carcinoma of the
      pancreas.
AB  - OBJECTIVES: To evaluate whether a short radiation treatment (30 Gy, 3.0
      Gy/fraction) had analgesic efficacy in patients with unresectable pancreatic
      carcinoma. METHODS: Twelve patients were included in this analysis. Before
      starting and at four weeks after radiation therapy, pain intensity was evaluated
      and analgesic drug therapy was adjusted until a 0-3 pain score was reached (WHO).
      RESULTS: No radiotherapy interruptions, no hospitalisation due to toxic
      reactions, and no severe toxicity were observed. Six patients (50%) had pain
      control without pharmacological therapy, three patients (25%) reduced their use
      (35%-72%) of analgesics, while in the remaining three patients (25%) there was no
      change in analgesic use. Overall, mean reduction in the use of analgesics was
      63.1% +/- 43.8%. During follow-up (44 months), two patients (16.7%) showed a
      worsening of pain that required increased analgesia; in one patient, percutaneous
      splanchnicectomy was necessary. CONCLUSION: In patients excluded from standard
      concomitant chemoradiation, hypofractionated-accelerated radiotherapy is feasible
      and results in pain relief in most patients, documented as a reduced need for
      analgesics.

PMID- 14959597
TI  - Place of death and use of health services in the last year of life.
AB  - AIM: To investigate whether health service input in the last year of life differs
      between cancer patients who die at home versus those dying in inpatient care.
      METHODS: Post hoc exploratory case-control study of 127 home deaths and 200
      inpatient deaths. Retrospective electronic record linkage of patients' community
      and inpatient care during the last year of life. RESULTS: Patients who died at
      home began their home nursing care closer to death than those who died as
      inpatients. Their first contact with inpatient hospice care began further from
      death. Before their final month, home death patients also had more specialist and
      district nursing than patients who died in inpatient care. CONCLUSIONS: Patients
      who began their home nursing early were less likely to die at home than those who
      began such care late. This suggests that it may be difficult to sustain end-of
      life care at home for an extended period. Further research incorporating
      assessment of informal care input and disease trajectory is required to
      investigate this issue.

PMID- 14959598
TI  - French physicians' attitudes toward legalisation of euthanasia and the ambiguous
      relationship between euthanasia and palliative care.
AB  - In 1999, the French Parliament established a "right to palliative care", which
      reactivated public debate about euthanasia. In order to investigate jointly
      physicians' attitude toward palliative care and euthanasia, we conducted a cross
      sectional survey of a national sample of French GPs, oncologists, and
      neurologists. Overall, 917 physicians participated in the survey. Significant
      proportions of respondents, especially among GPs and neurologists, considered
      that palliative sedation and withdrawing life-sustaining treatments (WLST) were
      euthanasia. Multivariate analysis showed that the physicians who had special
      medical training in palliative care, and those who distinguish palliative
      sedation and WLST from euthanasia were more likely to oppose legalisation of
      euthanasia. Thus, French physicians' attitude to the legalisation of euthanasia
      is strongly influenced by whether or not they distinguish palliative care from
      euthanasia. Improved palliative care requires better training of the entire
      medical profession, and clearer guidelines about which end-of-life care practices
      are legally and ethically acceptable.

PMID- 14959599
TI  - Hydration management in palliative care settings--a survey of experts.

PMID- 14959600
TI  - Case study report of two palliative care patients receiving
      intracerebroventricular (ICV) analgesia.

PMID- 14959601
TI  - The AAFP cuts an EMR deal.

PMID- 14959602
TI  - Diagnosis coding tips.

PMID- 14959603
TI  - Don't buy home computers for the office.

PMID- 14959604
TI  - The new Medicare law. Doctors cheer.

PMID- 14959605
TI  - Malpractice rates. How high now.

PMID- 14959606
TI  - A rush to diagnosis.

PMID- 14959607
TI  - How to close a practice.

PMID- 14959608
TI  - "Doc, we need to pray.".

PMID- 14959609
TI  - How I beat an HMO.

PMID- 14959610
TI  - Evaluating new physicians.

PMID- 14959611
TI  - Conflict of interest?

PMID- 14959612
TI  - Bringing HCA back to life.

PMID- 14959613
TI  - Keep an eye on Weight Watchers.

PMID- 14959614
TI  - [Problems of exobiology: the origin of life on Earth].
AB  - The basic problem of exobiology is origin and evolution of life as a space
      phenomenon. Consideration is given to the facts for the space origin, spreading
      in the interstellar space of and invasion of the surface of planets by organic
      compounds, constituents of archetypes of living systems. The authors bring up to
      discussion the issues of life development under the conditions of Earth, and
      formation of the main properties of the living organisms differing in the level
      of organization. Outlined are some international projects on exobiological
      research in experiments with bio-objects on space platforms.

PMID- 14959615
TI  - [Measures for psychological prophylaxis of the psychogenic adaptation disorders
      among flying personnel].
AB  - Adaptation disorders lie behind 70 to 80% of morbidity among and medical
      disqualification of flyers. Mental health is the hallmark of the
      psychoprophylaxis system defining its structural and methodical principles, and
      purpose. Counteraction to the psych dependent adaptation disorders requires
      consolidation of efforts of the services responsible for flyers professional
      health and flight safety; emphasis on motivation and social well-being of flyers
      is imperative.

PMID- 14959616
TI  - [Means and methods of improving pilot's tolerance for g-loads following an
      extended flight in a one-seat fighter].
AB  - G-loads tolerance following hypodynamia during extended flights and effectiveness
      of countermeasures against possible negative impacts were studied. Subjects
      performed 5-hr simulated flights after which they were centrifuged with a g
      gradient of 0.1 u/s in the relaxed state, and with a g-gradient of 1.0 u/s at
      complex-profiled 2 to 9 units in anti-g suit VKK-15. Tested were three sets of
      countermeasures (A, B, C) combining the following methods: physical exercises,
      VKK-15 provided massage of the lower body, 30-s exposure to 5 g, use of the
      profiled stiff and cushioned seats, electrical stimulation of the back and waist,
      and an air-cushion. The countermeasures were applied every hour on flight.
      Hypodynamia during the five-hour fighter flight was shown to have a weak
      detrimental effect on the pilot's functional state, performance and g-tolerance
      which were tempered by the proposed combinations of countermeasures.

PMID- 14959617
TI  - [The effect of pharmacological hypohydration on g-tolerance].
AB  - A group of 6 subjects (25-45 y.o.) participated in the studies of the tolerance
      of lateral (chest-back, +Gx) and longitudinal (head-pelvis, +Gz) loads before and
      after pharmacological hypohydration. Moderate hypohydration (diminution of the
      circulating plasma volume by 14% and body mass by 2% on the average) induced by
      diuretics does not lead to a substantial loss in tolerance of +Gx up to 8.3 units
      but reduces the threshold of +Gz tolerance by 0.6 units. The scientific and
      applied sense of these data is that diuretics can be safely administered in the
      pre-launch period to prevent the negative effects associated with the beginning
      of space flight.

PMID- 14959618
TI  - [Hydro-mechanical effects on human blood vessels of rotations on a short-arm
      centrifuge].
AB  - Methods of mathematical modeling in the interests of gravitational therapy
      revealed a number of specific effects of the short-radius centrifuge (SRC) on
      human leg vessels. The concepts of local g-loads and local hydrostatic pressure
      during exposure to the gravitational and inertial forces have been formulated.
      Experimental data suggest a squared dependence of local hydrostatic pressures
      (including in the pathology focus) on the radius of rotation; extra asymmetric
      oscillations of main vessels, point to the effects of the Coriolis acceleration
      of blood on vascular walls.

PMID- 14959619
TI  - [Dynamics of local oxygen consumption an extraction under the condition of
      altered oxygen turnover in humans during head-down bed rest].
AB  - Invasive and non-invasive measurements were used to evaluate methods of
      correcting oxygen consumption and extraction within the local circulation in
      bedrested human subjects. For the first time demonstrated was the vanity of
      attempts to improve O2 supply to the human peripheral tissues by re-establishment
      of the circulating blood volume and increasing oxygen content in the affluent
      blood. The reason can be that HD bed rest impacts the ability of peripheral
      tissues to augment consumption of the surplus oxygen. The experiment showed that
      preliminary infusion of an antihypoxant (gamma-hydroxibutyric acid) recovers this
      ability even in case of abundant oxygen. Based on results of the investigation,
      oxygen supply correction can be considered as a way to improve (when necessary)
      oxygen supply to the human peripheral tissues during HD bed rest.

PMID- 14959620
TI  - [Effects of two-week suspension on the dynamics of low-frequency arterial
      pressure fluctuations in intact rats and rats after sympathectomy].
AB  - Spectral analysis was used to study the dynamics of low-frequency hemodynamic
      fluctuations in male Wistar rats following 2-wk tail-suspension. The experiment
      was performed with intact rats and rats with the sympathetic nervous system
      damaged by 6-hydroxidofamine injection. Equally in intact and desympathetized
      animals, low-frequency fluctuations of arterial pressure (AP) were found less
      intensive within the 0.1 Hz region during and immediately after suspension.
      Beyond that, the intact rats exhibited decreases in the AP fluctuations coherence
      and pulse interval in this spectral region. Results of the investigation indicate
      that simulated gravitational unloading of rats produces changes in the dynamics
      of the low-frequency AP fluctuations; however, some part of these changes are not
      controlled by the sympathetic nervous system.

PMID- 14959621
TI  - [Peculiarities of eye morphogenesis in embryonic Japanese quails developed in
      microgravity].
AB  - This work is a part of comprehensive research into the effects of space flight on
      Japanese quail ontogenesis. Analysis of eye morphogenesis in the embryonic
      Japanese quails developed in microgravity discovered considerable deviations and
      abnormalities. Ocular abnormalities in the embryonic quail were mainly micro
      ophthalmic and associated with disproportional growth of the pigmental epithelium
      and neural retina which resulted in plication and a broken sandwich structure of
      the retina.

PMID- 14959622
TI  - [Psychosomatic evaluation of primates with the use of a psychomotor testing
      system].
AB  - The higher nervous system reactions of rhesus monkeys to the head-down tilt (HDT,
      28 d, -5 degrees) and preventive centrifugation were evaluated with the use of a
      computerized psychological testing system (PTS). Prior to HDT, the primates
      elaborated conditioned instrumental food-obtaining reflexes by playing computer
      games. Drilled to perform PTS tests to the best of their ability, the animals
      were to fulfill two PTS tests of increasing complexity in HDT. Test results were
      used to determine the dynamics of primates' cognitive function and the
      psychological state. The investigation consisted of two series with two groups of
      monkeys in each series. Twelve animals of each group (10 had skill in performing
      the PTS tests) were distributed into 2 subgroups. Every other day one of the
      subgroups was exposed to centrifugation at 1 to 2.5 g. In the first series, 10
      monkeys worked on the simplest test, i.e. spotting a static object. All animals
      showed interest in the computer game, and played a lot and successfully during
      HDT. In the second series, the animals were challenged with a more difficult test
      of following a moving object with the cursor. Based on the analysis of
      experimental data, a significant variability in achievement and emotional
      behavior of the primates should be attributed to different types of the nervous
      system.

PMID- 14959623
TI  - [Consideration of the deuterium-free water supply to an expedition to Mars].
AB  - Interplanetary missions, including to Mars, will put crews into severe radiation
      conditions. Search for methods of reducing the risk of radiation-induced cancer
      is of the top priority in preparation for the mission to Mars. One of the options
      is designing life support systems that will generate water with low content of
      the stable hydrogen isotope (deuterium) to be consumed by crewmembers.
      Preliminary investigations have shown that a decrease of the deuterium fraction
      by 65% does impart to water certain anti-cancer properties. Therefore, drinking
      deuterium-free water has the potential to reduce the risk of cancer consequent to
      the extreme radiation exposure of the Martian crew.

PMID- 14959624
TI  - Back to the basics. Number of general hospitals grows for the first time in years
      despite slim margins, lagging reimbursements and a tight market.
AB  - After slipping 16.5% in the past quarter-century, the number of community
      hospitals is on the rise despite slim margins, lagging reimbursements and a tight
      capital market. Growth is spurred by the attractive demographics of fast-growing
      suburban areas, changing consumer tastes and the lure of big business from baby
      boomers and the elderly. One new facility is Florida Hospital-Flagler, left.

PMID- 14959625
TI  - Hospitals propel spending. Report not expected to endanger reimbursement.

PMID- 14959626
TI  - Growing by leaps and bonds. Not-for-profits sell more despite weak ratings.

PMID- 14959627
TI  - Waging war. CMS policy moves hospitals to apply for reclassification.

PMID- 14959628
TI  - Blues boom. Anthem, WellPoint deal proceeds despite challenges.

PMID- 14959629
TI  - Too big? Caremark, AdvancePCS getting close look from feds.

PMID- 14959630
TI  - Ratio law hits hard in Calif.

PMID- 14959631
TI  - Information transformation. Baylor Health Care unveils initiative to make care,
      doctors more computer-savvy.

PMID- 14959632
TI  - False claim included. S.C. hospital pays settlement for exclusion violations.

PMID- 14959633
TI  - Blaming the messenger. Ernst & Young under fire for alleged bad billing advice.

PMID- 14959634
TI  - Specialty hospital ban was premature. Studies would have shown whether those
      facilities help or harm healthcare.

PMID- 14959635
TI  - Politics front and center. Expect plenty of heated rhetoric from Washington, but
      election-year posturing and growing deficits make major new initiatives unlikely.

PMID- 14959636
TI  - Taking it to heart. Availability of emergency angioplasty could be key to best
      outcomes for heart attack patients--but offering the service might not be so
      healthy for a hospital's finances.

PMID- 14959637
TI  - [Laparoscopic treatment of acute cholecystitis. Incidence of anatomo-clinical
      variations (271 cases)].
AB  - The study is based on 1050 laparoscopic cholecystectomies for gallstones
      performed between 1991-1999, out of which 271 were preoperatively considered as
      acute cholecystitis (25.8%). The clinical, biological and ultrasound criteria
      were rigorously respected. The preoperative period of 1 to 5 days (mean--2.5) was
      used for re-equilibration and antibiotic and antithrombotic therapy. The
      intraoperative criteria were clinical, echolaparoscopical, cholangiographical and
      bacteriological and established in 219 cases the diagnostic of acute
      cholecystitis. The final diagnostic, on histopathological basis, confirmed the
      preoperative diagnosis of acute cholecystitis in 224 cases. The microscopical
      reexamination in the remainding controversy cases reclassified other 18 as acute
      cholecystitis (final concordance ratio--242:271). The preoperative overvaluation
      may be consecutive to a too rapid (before the constitution of specific lesions)
      or too delayed intervention (the aspect becoming chronical). The elements of
      diagnostic discordance are raising the problem of case selection and the
      necessity for standard classification of histological lesions in acute
      cholecystitis.

PMID- 14959638
TI  - [Considerations on 988 breast cancers].
AB  - AIM: Therapy schedule improvement. MATERIAL & METHOD: The study includes 988
      patients (which 16 men) with breast cancer who underwent surgery between 1984
      1998. Out of them 63.2% were in advanced stages. The patients were divided in 2
      homogenous groups: trial A = 520 patients treated between 1984-1991 (in stade: I
      = 2, II = 240, III = 246, IV = 32) studied retrospectively, and trial B = 468
      patients treated between 1992-1998 (in stade I = 3, II = 212, III = 235, IV = 18)
      studied prospectively. In trial B the complex therapy schedule was improved
      according to disease's stade, local breast aspect and patient's biological
      status, straining on neoadjuvant therapy. To the entire group 945 radical
      mastectomies (95.6%) were performed. Only 628 (63.5%) could be properly followed
      up. RESULTS: Global 5 years survival rate was 72% (improved from 69% in trial A
      to 72% in trial B). The survival rate varied according the stage from 100% (stade
      I), 88% (stade II), to 22% (stade III) and 2% (stade IV). In the advanced states,
      the local recurrencies at 5 years were of 22% and the methastases of 17%.
      CONCLUSIONS: The neoadjuvant therapy, selectively applied upon stade and patient
      improves the 5 year survival rate. Every patient with an advanced breast cancer
      can benefit of a complex, differentiated and well guided treatment. The adequate
      operation earn the important role in powering the neoadjuvant and adjuvant
      therapies. Further results improvement requires restarting the collectivities and
      high risk persons screening.

PMID- 14959639
TI  - [Post-caustic esophageal stenosis].
AB  - This study treats the last 13-year experience of the Surgical Department from the
      Fundeni Hospital Bucharest (Romania) regarding the surgery of the postcaustical
      esophageal stenoses. The series is composed of 25 patients (10 males and 15
      women), with ages between 19 and 58 years. The patients were admitted in our unit
      at an interval between 2 months and 20 years from the caustical ingestion. In 20
      cases we preferred seriate procedures (gastrostomy or jejunostomy as a first
      operation, followed after 2 months to 20 years by a reconstructive procedure).
      The reconstructive operation was accompanied by resection of the stenotic
      esophagus in 15 cases (60%); in 10 cases we performed a bypassing (without
      resection) presternal esophagoplasty. Resection of the esophagus implied a
      combined abdomino-thoracic approach in 10 cases and an cervico-thoraco-abdominal
      approach in 5 (depending upon the extent of the lesions). The early postoperative
      course was complicated by anastomotic leakage's in 5 patients (20%) and by
      pulmonary complications in another 5 (20%) cases. There were no postoperative
      deaths. The late follow-up showed a good functional result in 24 patients with
      medium weight gain of 2.6 kilograms and a normal social reintegration. In
      conclusion, we consider that the esophagus resection in postcaustical stenoses is
      indicated when there are no counterindications, with a low morbidity when it is
      performed in specialized surgical services.

PMID- 14959640
TI  - [Sacrococcygeal teratoma in children. Anatomo-clinical, therapeutic and
      prognostic considerations].
AB  - Presentation of potentially malignant tumours, highly frequently found in
      children, developed out of embrionary remnants. Study of clinical observation
      files, iconography resources, histopathological samples and surgical operation
      notes, corroborated with patient's reexamination several years later. There are
      presented nine clinic cases of tumours found in newborn, babies and even in young
      children, with teratome-like structure, that have malignant potential if excised
      late. Histopathological laboratory tests of the biotic sample are of paramount
      importance in establishing the structure of the tumour, its malignization
      abilities and the therapeutical conduct to be adopted. Other useful
      investigations: radiographs of the vertebral column, abdominal echographs,
      computerized tomography. Besides sacrococcygian, large and anesthetic, location
      in newborn, there are presented cases of intra-abdominal teratomes and one case
      of ovarian teratome. The study also contains a general opinion upon the patients
      operated on the reexamined several years later.

PMID- 14959641
TI  - [Surgical treatment of pelvic subperitoneal tumors].
AB  - In the last 5 years in our hospital was operated 25 patients with
      pelvisubperitoneal tumors. Major clinical symptoms are compression and body mass
      effect. The localization and tumors dimensions, are established by CT and RMI.
      Surgical resection, difficult by the relations with iliac vessels and nerves, was
      do it in sub capsular manners and followed by chemo and radiotherapy. Our results
      are good, with 6 patients who passed 4 years postoperatively.

PMID- 14959642
TI  - [Giant retroperitoneal lipoma].
AB  - 70 retroperitoneal tumors (10 with an adipous origin out of which 8 were lipomas)
      have been operated upon in our clinic since 1985. Four cases of giant lipomas are
      presented in this paper. They weighed 4.5-7.5 kg. and had a diameter over 15
      centimeters. Their close proximity with the kidney, duodenum, colon, inferior
      vena cava etc made there extirpate difficult. The post-operative condition of the
      patients was good. Although the histopathological tests proved that all these
      giant lipomas were benign after two to four years, their relapse required a new
      surgical intervention. The histopathology of the relapsed lipomas revealed a
      malign degeneration in 3 out of the four cases. The origin of this malign
      degeneration was in the fibrous part of the tumors.

PMID- 14959643
TI  - [Klatskin unresectable tumour. Palliative treatment or no surgical operation?].
AB  - The Klatskin tumor is a neoplasy of the proximate main biliary duet whose initial
      manifestation, and most of the time, the single one, consist in the appliance of
      an obstructive nature jaundice. This usually coincides with the spreading of the
      tumor beyond the walls of the tumors that have reached this state with a usually
      intraoperating made diagnosis, certain palliative technical surgery solutions
      could still exist. The author submits to your attention a retrospective survey on
      85 tumors out of which only 3 were removable. For the remaining 82 he performed
      only exploratory laparotomy. Of these biopsy was made for 11 cases and palliative
      surgery for the other 71 (biliodigestive derivations on one or both liver lobes,
      or Huguet, Terblanche or Kehr tube surgery prosthesis operations). If the
      patient's living conditions are very good, his survival chances might be extended
      from 2 to 18 months, with no appearance of jaundice or pruritus. There is no
      doubt that if the pre-operations imagery testing results in the diagnosis
      "inoperable medical condition", the retrograde endoscopic transtumoral surgery
      prosthesis operation or the transparietal liver one, is recommended.

PMID- 14959644
TI  - [Congenital choledochal cysts. Observations on 2 operated cases].
AB  - The authors present two cases of congenital choledochal cysts treated by cyst
      excision with Roux-en-Y hepaticojejunostomy, followed by good postoperative
      results. One of the patients has been treated by early excisional procedure,
      while the other has initially undergone an enteric drainage by cystoduodenostomy,
      followed by complications, which required reoperations after 18 months. We have
      evaluated the peculiarities of both cases, the present data revealed by
      literature regarding biliary carcinogenesis related to congenital choledochal
      cysts, their classification according to pancreatobiliary malunion, as well as
      the treatment of choice in choledochal cysts, meaning excisional procedure with
      Roux-en-Y hepaticojejunostomy to prevent the risk of postoperatory complications
      which might appear after plain enteric drainage of the cyst.

PMID- 14959645
TI  - [Original contributions to study and treatment of intrathoracic goiters].

PMID- 14959646
TI  - [Gastrojejunocolic fistula after transmesocolic gastrojejunostomy for stenotic
      duodenal ulcer].
AB  - The authors are presenting the case of a 53 year-old patient, suffering from type
      II diabetes mellitus and ankylosing spondylitis, admitted in our clinic in July
      1997 for gastrojejunocolic fistula, 5 years after a transmesocolic
      gastrojejunostomy for obstructive chronic duodenal ulcer. The severe metabolic
      disorders and the radiologic aspects which led to the diagnosis, as well as the
      morphopathologic lesions found and the ways to approach the fistula, the stenotic
      duodenal ulcer and the reconstruction of the digestive continuity in a single
      surgical procedure are further discussed. The conclusions are shown at the end.

PMID- 14959647
TI  - [Esophagoplasty with right ileocolon, technical problems].
AB  - The authors present their experience with 14 cases of esophagoplasty by right
      ileocolon interposition which were performed to re-establish the digestive
      continuity in 12 patients operated on for caustic burns induced esophageal
      strictures and 2 patients with esophageal neoplasm managed by esophagectomy. The
      current study aims to pin/point both the anastomotic risk and the technical
      difficulties related to the colon interposition graft anatomic trajectory and
      vascular supply. Given the utmost importance of both the preoperative correction
      of the nutritional deficit and the improvement of pulmonary function the authors
      suggest that esophagoplasty should bu preceded by a "preoperative intervention",
      consisting of ileocolic artery ligation, gastrostomy and pleural drainage. The
      acute respiratory failure was the immediate main threat following esophagoplasty,
      whereas cervical anastomotic breakdown was the complication which dominated the
      early postoperative period in terms of frequency and gravity, but the death rate
      was nil. When esophagoplasty by right ileocolon interposition simplicity and
      efficacy are taken into account it appears as the surgical therapy of choice
      whenever the local and general status of the patients allows it.

PMID- 14959648
TI  - [Technical solving variants of external biliary and pancreatic fistulas].
AB  - Two cutaneous postoperative fistulas--pancreatic and biliary--was solved by an
      anastomosis of maturate fistulas traject with duodenum and respectively an Y
      jejuno loop (Roux) with good results.

PMID- 14959649
TI  - [Posterio-median approach in ventral tumor compression of the spinal cord].
AB  - The paper describes two types of resection of primary and metastatic spinal
      tumors via a posterolateral approach: by curettage and en-block resection. The
      outcomes of treatment in 15 patients operated on by curettage and 2 patients
      undergone en-block resection are analyzed. Postoperative pain relief was noted in
      100% of the patients. Six (55%) patients who had not been able to move became
      outpatient after surgery. There was a neurological improvement in 5 (29%)
      patients, i.e. they were at a higher stage by the Frankel scale. The above
      results show that removal of spinal tumors via posteriomedian access with lateral
      extension by curettage or en-block resection might be effective in surgically
      treating this pathology. Choice of a type of surgery (carcinological or
      palliative) primarily depends on the histological nature of a tumor, on the
      degree of neurological deterioration, on the extent and site of a tumorous
      process, and on the expected survival of a patient.

PMID- 14959650
TI  - [Modified anteriolateral retroperitoneal approach for surgical treatment of
      patients with compression of the cauda equina and lumbar nerve roots (topographic
      anatomical study)].
AB  - Mini-invasive techniques have been increasingly used in lumbar surgery in the
      past decade, most commonly during operations on the intervertebral disks.
      However, mini-invasive interventions may be used as a modified traditional
      approach to treating more serious and challenging pathology, such as tumors of
      the lumbar vertebrae, metastatic disease, as well as lumbar fractures of
      different origin. In the literature, there are only several papers on the mini
      invasive anterolateral retroperitoneal approach (ALMIRA) to corpectomy with
      repair of the lumbar spine. This paper deals with the autopsy of 15 cadavers
      (aged 55-83 years) and 5 blocks of the lumbar spine. The approach is described
      with illustrations being given. All the results are analyzed and shown in a
      table. Fifteen corpectomies of L2, L3, and L4 vertebrae were performed by ALMURA,
      using a self-retaining retractor. The duration of a procedure from skin incision
      to complete preparation of a spinal specimen for retractor's attachment averaged
      50 min (30-70 min). The corpses were rotated in the axial plane at 45, 35, and 25
      degrees for corpectomy of L2, L3, L4, respectively. The procedure was easier-to
      use when convex binding of the spine was performed after the approach and before
      insertion of a retractor, in obese cases in particular. Damage to the peritoneum
      occurred in 5 cases, that to the ascending lumbar vein took place in 4 (during L4
      corpectomy) and m. psoas in 2 cases, both in a cachectic cadaver. In the authors'
      opinion, the method is effective, but before applying it in the clinical theater,
      spinal surgeons should be well trained under experimental conditions.

PMID- 14959651
TI  - [Postoperative assessment of the efficiency of the radical removal of
      glioblastomas in the cerebral hemispheres].
AB  - The paper analyzes the capacities of computed tomography (CT) and magnetic
      resonance imaging (MRI) in the postoperative period to evaluate the efficiency of
      surgical removal of the most malignant type of gliomas of the cerebral
      hemispheres. A total of 45 patients with different histological forms of cerebral
      hemispheral gliomas were examined, 37 of them with glioblastomas. Comparison of
      the results obtained by CT and MRI within the first 24 hours indicated that the
      latter was of greater informative value in all cases. At the same time only the
      use of a strict methodological approach to postoperatively estimating the
      remaining portions of glioblastomas makes it possible to apply these two methods
      as objective criteria for evaluating the efficiency of removal of a glioblastoma
      and hence the efficiency of subsequent therapeutic protocols. Contrast-enhanced
      MRI may be regarded as the method of choice in the primary assessment of patients
      with suspected recurrent glioblastoma.

PMID- 14959652
TI  - [Clinical manifestation and outcomes of concussion of the brain: comparison of
      the results in patients admitted to hospital and in those who have refused
      admission].
AB  - The clinical manifestations and outcomes of concussion of the brain (CB) were
      comparatively analyzed in two groups of victims with acute brain injury (BI):
      those who had admitted to hospital and in those who had refused admission. A
      total of 355 individuals aged 16-35 years without concomitant somatic and
      neurological diseases were examined. The follow-up lasted 1 year. Clinical and
      neurological studies, computed tomography, and MR-imaging were used. In the acute
      period, the regression of neurological symptomatology and the better status of
      health were noted in the victims of both groups almost at the same time (on days
      4-6 after injury). The psychovegetative syndrome was the basis of neurological
      disorders in the victims from both groups in the posttraumatic period. The follow
      up has provided evidence for nearly equal numbers of victims with CB in both
      groups 1 year after BI.

PMID- 14959653
TI  - [Neuropsychological studies of patients with Parkinson's disease after
      stereotaxic operation on the subcortical nuclei].

PMID- 14959654
TI  - [Preoperative embolization of the internal carotid artery in surgical treatment
      of meningioma in the base of the anterior and middle cranial fossae].
AB  - Preoperative embolization is a widely used technique that may decrease blood
      supply to rich-vascurized tumors of the brain. Its use allows a neurosurgeon to
      safely remove a tumor of different histological nature and site. The objects of
      preoperative embolization are most commonly meningiomas at convexital or
      parasagittal sites. According to the data available in the literature, the
      internal carotid or ocular artery was embolized in not more than 10 cases. The
      described case underwent successful embolization of the involved internal carotid
      whose branches took an active part in supplying blood to the meningioma of the
      base of the skull. This permitted total resection of a generalized meningioma of
      the anterior and middle parts of the base of the skull.

PMID- 14959655
TI  - [Hemangioblastomas of central nervous system].
AB  - Hemangioblastomas of the central nervous system are benign, richly blood-supplied
      tumors that may be encountered in its any part, more commonly in the cerebellar
      hemispheres. Supratentorially, they occur rarely. In the literature there are
      reports on less than 100 cases of tumors at this site. The histogenesis of
      hemangioblastomas has not been clearly ascertained so far. Magnetic resonance
      imaging is the only valid diagnostic study of hemangioblastomas.
      Hemangioblastomas may be presented as sporadic forms and a manifestation of the
      Hippel-Lindau syndrome. In the latter case, hemangioblastomas are associated with
      angiomas of the retina and other viscera. Surgery of hemangioblastomas is the
      basic treatment. Radiosurgery is the method of choice for patients with Hippel
      Lindau disease. The main cause of postoperative death is bleeding to the brain
      stem and the remaining portions of the tumor. Endovascular embolization of the
      vessels supplying blood to the tumor may be used to diminish postoperative
      bleeding. Recurrences are mainly associated with incomplete surgical tumor
      removal. Chemotherapy is not indicated in hemangioblastomas. Radiation therapy
      may be used after partial tumor removal.

PMID- 14959657
TI  - A political prescription.

PMID- 14959656
TI  - [The first conference on pediatric neurosurgery].

PMID- 14959658
TI  - Rethinking weight.

PMID- 14959659
TI  - Fighting for a forgotten forest.

PMID- 14959660
TI  - Playing chicken with the flu.

PMID- 14959661
TI  - American Diabetes Association resource guide 2002. Urine testing.

PMID- 14959662
TI  - American Diabetes Association resource guide 2002. Manufacturers and exclusive
      distributors.

PMID- 14959663
TI  - A new year's wish: "healthy endothelium".

PMID- 14959664
TI  - Fast food & restaurant fare. Denny's.

PMID- 14959665
TI  - Healthy eating. Tropical breezes.

PMID- 14959666
TI  - Cold winter? The gym offers hot workouts.

PMID- 14959667
TI  - Honor yourself. Retire the superwoman.

PMID- 14959668
TI  - "K-ration". Diabetes and cardiovascular risk.

PMID- 14959669
TI  - Fast food & restaurant fare. Boston Market.

PMID- 14959670
TI  - King of the Blues. B.B. King has now been at the top of the blues game for more
      than 50 years.

PMID- 14959671
TI  - Class action. There are now five classes of diabetes pills. Each has a different
      way of helping you control your diabetes.

PMID- 14959672
TI  - Fighting diabetic kidney disease. The best defense is a good offense--take action
      now to prevent kidney disease.

PMID- 14959673
TI  - Research profile. Genetics and heart disease. .

PMID- 14959674
TI  - Health eating. A chicken in every pot.

PMID- 14959675
TI  - Good control drastically cuts eye disease rates.

PMID- 14959676
TI  - Combination meter and doser released.

PMID- 14959677
TI  - Smokin' diabetes blues.

PMID- 14959678
TI  - HRT for hearts? Research raises new questions.

PMID- 14959679
TI  - Fast food & restaurant fare. Arby's.

PMID- 14959680
TI  - Teen forum. Preventing complications.

PMID- 14959681
TI  - A diabetes primer. Diabetes is a complex disease. Here's how it works and what
      you can do to take control of it.

PMID- 14959682
TI  - Yes, I have diabetes. Consuelo Hernandez.

PMID- 14959683
TI  - Diabetes camp. An option you might not have considered...

PMID- 14959684
TI  - The diet craze. Setting the record straight on high-protein, low-carbohydrate
      diets.

PMID- 14959685
TI  - Research profile. A troublesome triangle.

PMID- 14959686
TI  - Healthy eating. Make it now, serve it later.

PMID- 14959687
TI  - As the worm turns. On diabetes and obesity.

PMID- 14959688
TI  - Slowing down.

PMID- 14959689
TI  - New trends in HIV disease worldwide.

PMID- 14959690
TI  - Condoms block HIV.

PMID- 14959691
TI  - Cardiovascular disease in a patient with AIDS.

PMID- 14959692
TI  - The continuing evolution of HIV therapy.

PMID- 14959693
TI  - Quality of life and HIV: current assessment tools and future directions for
      clinical practice.
AB  - Routine clinical assessment of health-related quality of life in persons with HIV
      infection has the potential to improve care by assessing and monitoring treatment
      effects, enhancing communication between patient and provider, and tracking
      changes in functional status over time. Currently available research-based
      assessment tools may be inadequate for routine clinical use because of the lack
      of inclusion of HIV-relevant aspects of quality of life and the impracticality of
      the use of such tools in the clinical setting. There may be a need for a new,
      clinically relevant, HIV-specific assessment tool that would be easy to
      incorporate into clinical practice to briefly, yet comprehensively, assess
      characteristics frequently found in HIV-infected persons, such as fatigue, pain,
      nausea and vomiting, sleep disturbances, sexual dysfunction, and body image
      issues. Until such a tool is developed, the Linear Analogue Self-Assessment
      questionnaire and the Medical Outcomes Study Short Form-12 (MOS SF-12) are short
      enough for routine use in a clinical setting. Slightly longer measures, such as
      the MOS-HIV Health Survey (MOS-HIV), can provide information in a greater number
      of domains.

PMID- 14959694
TI  - Current concepts of metabolic abnormalities in HIV patients: focus on
      lipodystrophy.
AB  - HIV infection is associated with a number of metabolic abnormalities, including
      lipodystrophy, a difficult-to-define disorder whose characteristics include
      hyperlipidemia, insulin resistance, and fat redistribution. Current data suggest
      that lipodystrophy is caused by multiple factors. Dual-nucleoside reverse
      transcriptase inhibitor therapy combined with protease inhibitor therapy has been
      shown to increase the risk of metabolic abnormalities, but susceptibility
      independent of drug effects has also been shown. While many of the treatments for
      the broad range of signs and symptoms of lipodystrophy bring about improvements
      in patient status, none have been demonstrated to bring about a return to
      baseline levels.

PMID- 14959695
TI  - Testosterone replacement for hypogonadism: clinical findings and best practices.
AB  - Hypogonadism is highly prevalent in HIV-infected patients and has been associated
      with the late stages of AIDS and AIDS wasting. There are a number of studies
      exploring treatment options. Testosterone replacement, with the exception of the
      transscrotal delivery patch, has been observed to have a beneficial effect on
      lean body mass and body weight in hypogonadal and eugonadal men with the AIDS
      wasting syndrome. Resistance exercise training also has had favorable effects on
      body weight and muscle cell mass. In hypogonadal men with AIDS treated with
      testosterone replacement therapy, researchers noted a positive effect on
      depression scores.

PMID- 14959696
TI  - Weight loss, wasting, and survival in HIV-positive patients: current strategies.
AB  - Wasting syndrome has been a common HIV-related condition reported in the United
      States. Three analyses from the Tufts Nutrition for Healthy Living study shed new
      light on the syndrome. Analysis of Cox proportional hazards models showed that
      losses in weight, fat-free mass, body cell mass, and fat mass, both from baseline
      weight and from weight at previous follow-up, were all significant indicators of
      mortality in patients with the HIV wasting syndrome. In the second analysis, the
      prevalence of 5% weight loss from the previous visit was shown to be 35% greater
      in the late HAART era, from 1998 to 2003, than in the early HAART era of 1995 to
      1997 (P < .02). This corresponds with earlier observations that the diagnosis of
      HIV wasting had been increasing during the decade of the 1990s. In the third
      analysis, the researchers found that body weight, fat-free mass, and body mass
      index improved in patients receiving nutritional intervention compared with
      patients receiving placebo.

PMID- 14959697
TI  - HIV therapeutics in children and adults and their side effects.

PMID- 14959698
TI  - Finding the balance.

PMID- 14959699
TI  - Can AIDS drug also prevent HIV infection?

PMID- 14959700
TI  - Lipid abnormalities during ART: it's the drug, not the class.

PMID- 14959701
TI  - A case-control study of gynecomastia in HIV-1-infected patients receiving HAART.
AB  - Gynecomastia has been reported to occur in HIV-infected patients receiving HAART.
      A retrospective case-control study was conducted to determine risk factors
      associated with this condition. Two control patients were randomly chosen for
      each of 23 case patients identified. An efavirenz-containing regimen was strongly
      associated with the development of gynecomastia (odds ratio, 20; P < .001). Case
      patients were not more likely to have lipodystrophy, low testosterone levels,
      chronic infection with hepatitis B or C virus, or liver dysfunction compared with
      control patients. None of these factors altered the efavirenz-associated risk
      when analyzed by multiple logistic regression. Efavirenz appears to be strongly
      associated with gynecomastia in HIV-infected patients receiving HAART.

PMID- 14959702
TI  - Editorial comment: unraveling the cause of HIV-related gynecomastia.

PMID- 14959703
TI  - Disseminated Acanthamoeba sinusitis in a patient with AIDS: a possible role for
      early antiretroviral therapy.
AB  - Acanthamoeba, a free-living ameba, has been reported to infect humans with
      subacute encephalitis, sinusitis, or keratitis. Multiple cases of Acanthamoeba
      sinusitis with dissemination have been reported in association with AIDS, with
      high mortality. We report successful treatment of a 35-year-old woman who
      presented with sinusitis that progressed to disseminated acanthamebiasis as her
      initial manifestation of AIDS. To our knowledge, our patient was one of the few
      and longest-lived survivors of disseminated Acanthamoeba infection with AIDS. As
      with other opportunistic infections, early aggressive therapy including HAART may
      alter the outcome in this almost uniformly fatal disease.

PMID- 14959704
TI  - Editorial comment: Acanthamoeba infection--a fatal opportunistic infection.

PMID- 14959705
TI  - Expression of inducible nitric oxide synthase in smooth muscle cells from rat
      penile corpora cavernosa.
AB  - Nitric oxide (NO), the main mediator of penile erection, is assumed to be
      synthesized in the penis by the neuronal constitutive nitric oxide synthase
      (nNOS). However, nNOS has not been identified in the penile smooth muscle, the
      target of NO action. The other NOS isozymes, the inducible NOS (iNOS) and the
      endothelial NOS (eNOS) have not been reported in any penile tissue. The smooth
      muscle vascular and trabecular tissue from rat corpora cavernosa is represented
      in vitro by cell cultures designated RPSMC. To determine whether iNOS can be
      expressed in penile smooth muscle, RPSMC were treated with different lymphokines
      and/or bacterial lipopolysaccharide (LPS). The selected inducer, LPS/interferon,
      elicited at 48 hours up to a 50-fold increase in nitrites in the medium; the
      nitroarginine methyl ester (L-NAME), aminoguanidine, actinomycin D,
      cycloheximide, transforming growth factor-beta1 (TGF-beta1), and dexamethasone,
      but was resistant to nifedipine and platelet-derived growth factor AB (PDGF-AB).
      iNOS induction increased with cell passage. The [3H]L-arginine/citrulline
      measurement of NO synthesis with intact cells confirmed these results.
      Incubations of soluble and particulate fractions showed that the cytosol
      contained most of the activity (Km = 43 microM), which was partially inhibited by
      ethyleneglycal-bis-tetraacetic acid (EGTA). The 4.4-kb iNOS mRNA peaked at a late
      period (24-30 hours) and remained high for up to 72 hours. iNOS mRNA induction
      was strongly inhibited by actinomycin D and dexamethasone, partially inhibited by
      TGF-beta1, inhibited slightly by PDGF-AB, and unaffected by nifedipine. These
      results show that iNOS can be expressed in RPSMC in a cell passage-dependent
      fashion that has so far not been reported for other cell lines, and that the
      induction reaches much higher levels than in rat or human vascular smooth muscle
      cells. The expression pattern is also distinctive for the penile cells in time
      course of induction, Ca2+ dependence, response to certain agents, and mRNA
      stability.

PMID- 14959706
TI  - Is the unified list system for organ transplants fair? Analysis of opinions from
      different groups in Brazil.
AB  - In the 1960s, when Dr. Belding Scribner discovered how to accomplish the process
      of dialysis in a repeated way, he could not imagine that in solving such a
      problem others as or more difficult would appear. Given the technological
      progress and the impossibility of assisting all patients through the most modern
      methods, the medical doctor often finds himself faced with the moral dilemma of
      choosing which patient in the waiting list will receive the treatment. This same
      dilemma is amplified in the case of organ transplants. Professionals, students,
      professors of the juridical and health fields, and the population in general,
      were interviewed as a means of documenting the moral concepts and opinions
      surrounding this problem. In the reality in which we find ourselves, it seems to
      us that deciding who lives, and the responsibility for all the events that
      culminate in such decisions, is still a subject left open to discussion.

PMID- 14959707
TI  - Teaching global bioethics.
AB  - We live in a world with enormous disparities in health. The life expectancy in
      Japan is 80 years; in Malawi, 40 years. The under-five mortality in Norway is
      4/1000; in Sierra Leone, 316/1000. The situation is actually worse than these
      figures suggest because average rates tend to mask inequalities within a country.
      Several presidents of the IAB have urged bioethicists to attend to global
      disparities and to broaden the scope of bioethics. For the last six years I have
      tried to do just that. In this paper, I report and reflect on my attempts to
      teach bioethics in ways that address global health and justice. I then discuss
      ways to address key ethical issues in global health: the problem of inequalities;
      the nature of the duty to assist; the importance of the duty not to harm; the
      difference between a cosmopolitan and a political view of justice. I also discuss
      how teaching about global health may help to shift the emphasis in bioethics-
      from sensational cases to everyday matters, from autonomy and justice, and from
      access to healthcare to the social determinants of health. At the end of my
      paper, I reflect on questions that I have not resolved: how to delineate the
      scope of bioethics, whether my approach over-politicises bioethics, and how to
      understand the responsibilities of bioethicists.

PMID- 14959708
TI  - Philosophical arguments for and against human reproductive cloning.
AB  - Can philosophers come up with persuasive reasons to allow or ban human
      reproductive cloning? Yes. Can philosophers agree, locally and temporarily, which
      practices related to cloning should be condoned and which should be rejected?
      Some of them can. Can philosophers reproduce universally convincing arguments for
      or against different kinds of human cloning? No. This paper analyses some of the
      main arguments presented by philosophers in the cloning debate, and some of the
      most important objections against them. The clashes between the schools of
      thought suggest that philosophers cannot be trusted to provide the public
      authorities, or the general public, a unified, universally applicable view of the
      morality of human reproductive cloning.

PMID- 14959709
TI  - Stopping traffic.

PMID- 14959710
TI  - The vulnerable and the susceptible.
AB  - Human beings are essentially vulnerable in the view that their existence qua
      humans is not given but constructed. This vulnerability received basic protection
      from the State, expressed in the form of the universal rights all citizens are
      meant to enjoy. In addition, many individuals fall prey to destitution and
      deprivation, requiring social action aimed at recognising the specific harms they
      suffer and providing remedial assistance to palliate or remove their plights.
      Citizens receive protection against their biologic vulnerability by means of an
      in rem right to health [care], which is more an attitude of protection than a
      specific programme. When individuals become susceptible, that is, biologically
      weak or diseased, they also increase their predisposition to additional harm, and
      require social actions to treat their demeaned condition. Such assistance takes
      the form of positive healthcare rights. Research on human beings has been slow to
      observe that the subjects recruited are susceptible, especially so if research is
      done in less developed countries. By mislabelling them as vulnerable--a
      characteristic they share with all humans--sponsors avoid registering the
      deprivation these people suffer, and the ethical obligation to offer them
      remedial help. The distinction between vulnerability and susceptibility also
      marks the difference between being intact but fragile--vulnerable--and being
      injured and predisposed to compound additional harm--susceptible. Awareness of
      this difference should give additional force to the rejection of double standards
      in research ethics.

PMID- 14959711
TI  - Keeping it close to home with imby.

PMID- 14959712
TI  - Sport-caught fish and breast cancer. Angling for more data.

PMID- 14959713
TI  - A new mechanism for chlorpyrifos? Implicating serotonin.

PMID- 14959714
TI  - The danger of extrapolation. Humans and rodents differ in response to PCBs.

PMID- 14959715
TI  - [Computed tomographic colonoscopy to screen for colorectal neoplasia in
      asymptomatic adults].

PMID- 14959716
TI  - Bioethics, vulnerability, and protection.
AB  - What makes individuals, groups, or even entire countries vulnerable? And why is
      vulnerability a concern in bioethics? A simple answer to both questions is that
      vulnerable individuals and groups are subject to exploitation, and exploitation
      is morally wrong. This analysis is limited to two areas. First is the context of
      multinational research, in which vulnerable people can be exploited even if they
      are not harmed, and harmed even if they are not exploited. The type of
      multinational research likely to raise the most ethical concerns is that in which
      the investigators or sponsors are from a powerful industrialised country or a
      giant pharmaceutical company and the research is conducted in a developing
      country. Second is the situation of women, who are made vulnerable in cultural
      settings or in entire countries in which they are oppressed and powerless. In the
      face of cultural values and practices, or governmental policies, these women
      suffer serious consequences for their health and even lives. Examples are
      provided, and it is suggested that in some cases vulnerable individuals can be
      harmed but not exploited. On the positive side, recent developments reveal a new
      awareness of exploitation and efforts to enhance the ability of developing
      countries to protect themselves and their citizens from exploitation at the hands
      of powerful sponsors of research. In addition, human rights principles are
      increasingly being used to monitor the actions (or inaction) of governments
      regarding women's reproductive rights and vulnerability with respect to HIV/AIDS,
      and to take remedial actions.

PMID- 14959717
TI  - Public health ethics: asylum seekers and the case for political action.
AB  - This paper is a case study in public health ethics. It considers whether there is
      a basis in ethics for political action by health professionals and their
      associations in response to inhumane treatment. The issue arises from Australia's
      treatment of asylum seekers and the charge that this treatment has been both
      immoral and inhumane. This judgement raises several questions of broader
      significance in bioethics and of significance to the emerging field of public
      health ethics. These questions relate to the role of health professionals in
      response to inhumane treatment of people in their charge; to the discipline of
      public health in light of a growing recognition of its ethical basis; and the
      role of public health and bioethical associations in response to ethical issues
      arising in a political context. It is argued that, in serious cases of
      humanitarian and human rights abuses affecting health and well-being, there is a
      case for political action by health professionals, academic and professional
      institutions, and associations of public health and ethics.

PMID- 14959718
TI  - More breast cancer findings from the Women's Health Initiative.

PMID- 14959719
TI  - Two claims about potential human beings.
AB  - It seems that at conception something is formed which, due to its genetic make
      up, has the potentiality to develop into a full-blown human being. Many believe
      that in virtue of this potentiality, this organism, the human zygote or early
      embryo, has in instrinsic value which makes it wrong to use or produce it merely
      as a means to some end, e.g., some scientific end such as to produce embryonic
      stem cells. Against this it is here argued, first, that it does not follow from
      the fact that something has a potential to become a (fully developed) human being
      that it already is a human being (in a rudimentary sense). In fact, a human being
      begins to exist no earlier than a couple of weeks after conception, at the stage
      known as gastrulation. Thus, even granted the questionable assumption that
      something has instrinsic value in virtue of being a human being, the zygote will
      not have intrinsic value. Secondly, the value an embryo has in virtue of its
      potentiality to become a full-blown human being can only be instrumental, a value
      as a means. But of course it cannot be wrong to treat that which has merely
      instrumental value as a mere means or instrument to some end.

PMID- 14959720
TI  - Human cloning: category, dignity, and the role of bioethics.
AB  - Human cloning has been simultaneously a running joke for massive worldwide
      publicity of fringe groups like the Raelians, and the core issue of an
      international movement at the United Nations in support of a treaty to ban the
      use of cloning techniques to produce a child (so called reproductive cloning).
      Yet, even though debates on human cloning have greatly increased since the birth
      of Dolly, the clone sheep, in 1997, we continue to wonder whether cloning is
      after all any different from other methods of medically assisted reproduction,
      and what exactly makes cloning an 'affront to the dignity of humans.' Categories
      we adopt matter mightily as they inform but can also misinform and lead to
      mistaken and unproductive decisions. And thus bioethicists have a responsibility
      to ensure that the proper categories are used in the cloning debates and denounce
      those who try to win the ethical debate through well-crafted labels rather than
      well-reasoned argumentations. But it is as important for bioethicists to take a
      position on broad issues such as human cloning and species altering
      interventions. One 'natural question' would be, for example, should there be an
      international treaty to ban human reproductive cloning?

PMID- 14959722
TI  - Progestogens for menstrual migraine.

PMID- 14959723
TI  - Voluntary euthanasia: a utilitarian perspective.
AB  - Belgium legalised voluntary euthanasia in 2002, thus ending the long isolation of
      the Netherlands as the only country in which doctors could openly give lethal
      injections to patients who have requested help in dying. Meanwhile in Oregon, in
      the United States, doctors may prescribe drugs for terminally ill patients, who
      can use them to end their life--if they are able to swallow and digest them. But
      despite President Bush's oft-repeated statements that his philosophy is to 'trust
      individuals to make the right decisions' and his opposition to 'distant
      bureaucracies', his administration is doing its best to prevent Oregonians acting
      in accordance with a law that its voters have twice ratified. The situation
      regarding voluntary euthanasia around the world is therefore very much in flux.
      This essay reviews ethical arguments regarding voluntary euthanasia and physician
      assisted suicide from a utilitarian perspective. I shall begin by asking why it
      is normally wrong to kill an innocent person, and whether these reasons apply to
      aiding a person who, when rational and competent, asks to be killed or given the
      means to commit suicide. Then I shall consider more specific utilitarian
      arguments for and against permitting voluntary euthanasia.

PMID- 14959724
TI  - Can we help addicts become more autonomous? Inside the mind of an addict.
AB  - I examine the impact of addiction on autonomy in terms of the standard literature
      on addiction--referred to also as 'substance dependence.' Then in terms of the
      criteria for substance dependence, by developing a set of practical strategies to
      help people with addictions think more clearly, I test the idea of whether
      addicts can be helped to become more autonomous. Given that unsuccessful attempts
      to quit constitute part of the criteria of substance dependence, I look at what
      goes wrong when people try to quit using a substance. The subjective experience
      of addiction is an important aid in understanding addiction and first person
      accounts and literary characterisations of addiction provide insight into the
      addict's mind and assist us in deciding whether addicts can be helped to become
      more autonomous.

PMID- 14959725
TI  - Welfarism versus 'free enterprise': considerations of power and justice in the
      Philippine healthcare system.
AB  - The just distribution of benefits and burdens of healthcare, at least in the
      contemporary Philippine context, is an issue that gravitates towards two opposing
      doctrines of welfarism and 'free enterprise.' Supported largely by popular
      opinion, welfarism maintains that social welfare and healthcare are primarily the
      responsibility of the government. Free enterprise (FE) doctrine, on the other
      hand, maintains that social welfare is basically a market function and that
      healthcare should be a private industry that operates under competitive
      conditions with minimal government control. I will examine the ethical
      implications of these two doctrines as they inform healthcare programmes by
      business and government, namely: (a) the Devolution of Health Services and (b)
      the Philippine Health Maintenance Organization (HMO). I will argue that these
      doctrines and the health programmes they inform are deficient in following
      respects: (1) equitable access to healthcare, (2) individual needs for premium
      healthcare, (3) optimal utilisation of health resources, and (4) the equitable
      assignment of burdens that healthcare entails. These respects, as considerations
      of justice, are consistent with an operational definition of 'power' proposed
      here as 'access to and control of resources.'

PMID- 14959726
TI  - Self-management education of children with asthma: a meta-analysis.
AB  - Nearly one in every thirteen children has asthma, making it the most common
      chronic condition in childhood. For a variety of biological and environmental
      reasons, the prevalence of childhood asthma has risen dramatically in the past 20
      years, with disproportionate effects on low-income populations, minorities, and
      children living in inner cities. Much of the morbidity associated with childhood
      asthma, such as activity restrictions, missed school days, and emergency doctor
      visits, are preventable through appropriate management strategies. This Issue
      Brief summarizes evidence on the effectiveness of educational programs to improve
      self-management in children with asthma, and bolsters existing guidelines to
      include self-management education in the routine care of these patients.

PMID- 14959727
TI  - [Smallpox immunization in 19th century Brazil: inoculation, variolization,
      vaccine, and revaccination].
AB  - A product of the fear stirred by variola and the need to avoid contagion and
      spread of the disease, smallpox immunization has been a longstanding practice
      around the world, applied in different forms in different societies. Three
      methods have been used in Brazil-'variolization', Jennerian vaccination, and
      animal vaccination- prompting profound discord within the national medical
      community. The article endeavors to identify the main points of these debates, as
      found in the Gazeta Medica da Bahia and the Gazeta Medica do Rio de Janeiro,
      periodicals of note at the time and important spaces where those wielding medical
      knowledge and power sought legitimacy.

PMID- 14959728
TI  - Laparoscopic sutured anastomosis of the bowel.
AB  - BACKGROUND: Even though the safety and efficacy of sutured anastomosis have been
      proved in open surgery, laparoscopic sutured anastomosis is rarely performed
      because it is difficult and time-consuming. We aim at description of a
      standardized technique for laparoscopic sutured anastomosis of the bowel and
      definition of its learning curve. METHODS: Fifty-six laparoscopic sutured
      anastomoses of cow small intestine were performed in a laparoscopic simulator. In
      a survival animal trial, 10 end-to-end, 2 gastrojejunostomy, 2
      cholecystojejunostomy, 2 colocolic, and one side-to-side anastomoses were
      performed, using the same technique. RESULTS: In the survival cases, we had no
      leaks or obstruction, minimal adhesions, and only one stenotic gastrojejunostomy.
      The mean end-to-end anastomotic time was 50 min. The technique was suitable for
      most sites in the GIT. The learning phase required 40 anastomoses in the
      simulator. CONCLUSIONS: The described technique seems relatively fast, safe, and
      universal, and it needs about 40 anastomoses to be mastered.

PMID- 14959729
TI  - A novel method for gene delivery and expression in esophageal epithelium with
      fibrin glues containing replication-deficient adenovirus vector.
AB  - BACKGROUND: Gene transfer to the esophageal epithelium holds the potential for
      the therapy of malignant as well as premalignant lesions in the upper
      gastrointestinal tract. Replication-deficient recombinant adenoviruses represent
      an efficient means of introducing genes in vivo into cells in a variety of
      organs. The majority of in vivo studies utilize direct submucosal injection for
      delivery of the viral vectors into the locoregional area of the gut; transferring
      genes into epithelial cells, however, is difficult because viruses are retained
      in the subepithelial space. To establish the efficient method for gene transfer
      into the epithelial cells, we have developed a multiluminal spray catheter that
      can be passed through the accessory channel of an endoscope, and we have
      evaluated the feasibility of fibrin glues as a vehicle of recombinant
      adenoviruses in a porcine model. METHODS: The fibrinogen solution and the
      thrombion solution containing an E1/E3 deleted recombinant adenovirus expressing
      the bacterial lacZ gene (Ad-lacZ) were endoscopically sprayed on the porcine
      esophagus through the catheter attached to the dual-barrel syringe. Twenty-four
      hours after gene delivery, beta-galactosidase activity of the esophagus was
      determined under the microscope following X-gal staining. RESULTS: The fibrin
      glue could be locally sprayed on the porcine esophagus by using the multichannel
      catheter through the endoscope. Attachment of the fibrin glue comtining Ad-lacZ
      caused strong beta-galactosidase staining on epithelial cells in the mucosal
      surface, but not in the basal cell layer. CONCLUSION: Endoscopic local delivery
      of recombinant adenoviruses in aerosolized fibrin glues through a multiluminal
      catheter could provide an optimal technique for gene transfer into epithelial
      cells in the mucosal surfece, which may have important implications for the
      treatment of human esophageal premalignant diseases.

PMID- 14959730
TI  - Intrahepatic foreign body laparoscopic extraction.
AB  - An 11-month-old boy presented with an intrahepatic foreign body after ingestion
      of a sewing needle. Surgical management using an exclusive laparoscopic
      extraction was successful.

PMID- 14959731
TI  - Volvulus of the gallbladder: laparoscopic detorsion and removal.
AB  - A 73-year-old woman who presented with symptoms of acute cholecystitis was found
      to have a gangrenous gallbladder wrapped in three complete rotations around its
      pedicle. Detorsion and removal of the gallbladder were accomplished
      laparoscopically. Our review of the literature found no other case in which this
      degree of torsion was successfully treated laparoscopically.

PMID- 14959732
TI  - Laparoscopic transduodenal papillosphincteroplasty.
AB  - In the past 20 years, the approach to biliary lithiasis has changed tremendously
      as a result of advances in endoscopic and laparoscopic techniques. The two most
      important open surgical techniques involve extraction of the stones from the
      common bile duct combined with choledochoenterostomy and papillotomy followed by
      transduodenal papillosphinteroplasty. Ideally, the choledochotomy is followed by
      the insertion of a T-tube in the common bile duct. The transcystic approach has
      never been considered. The first endoscopic papillotomy was performed in 1973.
      Subsequently, it became the most widely used method for removal of common bile
      duct stones. In this report we explore the possibility of performing a
      laparoscopic transduodenal papillosphincteroplasty, following the strict rules
      commonly used in surgery. After cholecystectomy, a Fogarty catheter, is
      introduced through the cystic duct. This is followed by a minimal duodenotomy,
      then incision of the papillar sphincter. In this surgical proposal, we do not
      intend to substitute technique, but this method should be considered the ultimate
      solution in the laparoscopic approach to cholecystic choledocholithiasis.

PMID- 14959733
TI  - Diaphragmatic hernia resulting from injury during microwave-assisted laparoscopic
      hepatectomy.
AB  - A 31-year-old woman underwent microwave-assisted laparoscopic hepatectomy of the
      left lateral segment for focal nodular hyperplasia on January 14, 1998. On
      September 9, 1998, she felt continuous left abdominal pain and was admitted to
      our hospital for further examination. An upper gastrointestinal series showed
      converging folds of the greater curvature of the upper third of the stomach and
      craniad displacement of this portion. Thoracic magnetic resonance imaging showed
      herniation of the stomach into the pleural cavity. The patient was referred to
      our department, where she underwent surgery for a diaphragmatic hernia. The
      fundus of the stomach had escaped into the left pleural cavity through a defect
      in the diaphragm near where laparoscopic hepatectomy had been performed. The
      stomach was returned to the peritoneal cavity and the defect sutured. The
      patients postoperative course was uneventful. Although diaphragmatic hernia after
      laparoscopic surgery is a rare complication, with the performance of more
      advanced laparoscopic procedures and the use of higher-technology tissue
      destruction/hemostatic devices such as the microwave coagulator, more caution
      should be observed to prevent injury to adjacent organs such as the diaphragm.

PMID- 14959734
TI  - Ventriculopleural shunt: thoracoscopic placement of the distal catheter.
AB  - Ventriculopleural shunting is usually reserved for patients with limited options
      for shunt revisions. We report the case of a 16-year-old boy with posthemorrhagic
      hydrocephalus who required numerous shunt procedures. At the age of 6 years, a
      ventriculopleural shunt was inserted by an intercostal thoracotomy, and 4 years
      later replacement of the distal catheter was necessary. Recently, he presented
      again with a shunt malfunction due to migration of the pleural catheter. We
      describe a technique for performing the placement of the distal catheter under
      direct thoracoscopic vision by a peel-off needle into the unscarred thoracic
      cavity despite two previous pleural procedures. The postoperative course was
      uneventful. Thoracoscopic assistance in ventriculopleural shunt placement appears
      to be a safe and effective technique, offering several advantages over the open
      procedure: it is less invasive, allows a precise positioning of the thoracic
      catheter under visual control, and confirms appropriate function.

PMID- 14959735
TI  - Laparoscopic partial splenectomy for a splenic pseudocyst.
AB  - We describe a laparoscopic hemisplenectomy that was performed to treat a 21-year
      old patient with a large splenic pseudocyst located in the upper splenic pole.
      The diagnosis was made by computed tomography and ultrasound, and surgery was
      performed with ultrasound scalpel, clips, and fibrin glue. Surgery lasted 70 min
      and did not require blood transfusions. The patient was discharged on
      postoperative day 3, and at 28-month follow-up there were no sequelae or
      recurrences. The laparoscopic approach is a valid alternative to laparotomy
      because the integrated magnified view enables the surgical team to perform
      surgery in a much shorter time and with greater hemostatic accuracy than the
      traditional technique.

PMID- 14959736
TI  - Snaring of submucosal tumors of gastric fundus.
AB  - Submucosal tumors of the stomach are not uncommon. We present two cases of
      iatrogenic perforation after snaring large polyps in the gastric fundus. We
      discuss the probable etiology and review the literature regarding iatrogenic
      perforation in this location. Submucosal polyps situated in the fundus may
      produce pseudopedicle. Therefore, we recommend these be treated with caution, and
      a combined endoscopic and laparoscopic approach is suggested.

PMID- 14959737
TI  - Renal artery clip dislodgement during hand-assisted laparoscopic living donor
      nephrectomy.
AB  - The main reason for conversion in laparoscopic donor nephrectomy (LDN) is
      peroperative bleeding. One of the advantages of hand-assisted laparoscopic donor
      nephrectomy (HDLN) is facilitated control in case of bleeding. This report
      describes two methods to avert conversion in HLDN in the case of abrupt major
      arterial bleeding. In the first case, during left HLDN the clips placed on the
      renal artery dislodged, and the surgeon managed to control the bleeding by
      compressing the focus of the bleeding with his finger. A balloon occlusion
      catheter was inserted through a groin incision in the aorta and advanced to the
      origo of the renal artery. Due to control of the hemorrhage, it was possible to
      close the renal artery stump by laparoscopic suturing, and a conversion was
      averted. The patient was discharged after 5 days, without signs of damage to the
      remaining kidney. In the second case, during right HLDN, the clips on the renal
      artery dislodged during stapling of the renal vein. The bleeding was controlled
      by finger compression and new clips were placed. The cuff of the artery was long
      enough to be clipped again. The patient was discharged after 5 days. Graft
      function was excellent in both cases. Major arterial bleeding can be controlled
      and managed in hand-assisted laparoscopic surgery. The use of a balloon occlusion
      catheter is an elegant way to avert conversion.

PMID- 14959738
TI  - [The beginnings of the smallpox vaccine in Sao Paulo: a little known story].
AB  - This discussion of smallpox prevention practices in the state of Sao Paulo
      focuses primarily on the Instituto Vacinogenico, created in 1892 as part of a
      sanitation reform that modernized public health in Sao Paulo state. Established
      and headed until 1913 by the renowned Sao Paulo surgeon Arnaldo Vieira de
      Carvalho, the institute was responsible for statewide distribution of the
      smallpox vaccine derived from animals. It operated on its own until 1918, when it
      was made part of the Instituto Bacteriologico.

PMID- 14959739
TI  - Anastomotic recurrence of rectal adenoma after anterior resection.
AB  - Transanal local excision of posterior benign rectal tumors is usually safe. Here,
      we report a case of transanal excision of a posterior anastomotic recurrence of a
      rectal adenoma after a stapled anterior resection that resulted in perforation
      into the peritoneal cavity.

PMID- 14959740
TI  - An extrapleural approach to the anterior mediastinum using video-assisted
      thoracic surgery (VATS).
AB  - A lateral extrapleural approach via video-assisted thoracic surgery (VATS) was
      used in a patient suspected of having a benign tumor of right lobe of the thymus.
      The patient previously had undergone lung resection for pulmonary tuberculosis,
      and the ipsilateral thorax had contracted and dense pleural adhesions were likely
      to exist. Lateral extrapleural approach by VATS was performed successfully and is
      an alternative to open surgery in highly selected patients with anterior
      mediastinal lesions.

PMID- 14959741
TI  - Laparoscopic ureterolysis and reconstruction of a retrocaval ureter.
AB  - A 32-year-old man was investigated for repeated episodes of right-sided flank
      pain. Ultrasonography showed a dilated right pelvicalyceal system and upper
      ureter as well as multiple gallstones; subsequent intravenous urogram
      demonstrated a retrocaval ureter. At surgery, a right-sided double-J ureteric
      stent was placed under fluoroscopic guidance. Initially, three laparoscopic ports
      were used. The dilated pelvis and upper ureter were mobilized, followed by the
      lower ureter. The pelvis was transected and transposed anterior to the inferior
      vena cava. Reconstruction was carried out with an intracorporeally sutured
      anastomosis over the double-J stent. A fourth port was added for completion of
      cholecystectomy. The patient had an uneventful recovery and was discharged on the
      third day. Fourteen months later he remains well, with a recent intravenous
      urogram showing regression of hydronephrosis. We review the previously reported
      cases of laparoscopic and retroperitoneoscopic reconstruction of retrocaval
      ureter to compare and contrast these minimal access approaches.

PMID- 14959742
TI  - Pioneers in laparoscopic solid organ surgery.

PMID- 14959743
TI  - Slow-transit constipation after radical hysterectomy type III.

PMID- 14959744
TI  - Laparoscopic cholecystectomy in situs inversus totalis: The importance of being
      left-handed.
AB  - Since laparoscopic cholecystectomy has become the standard procedure for the
      treatment of gallstone disease, several cases have been reported in patients with
      situs inversus. These cases require more technically demanding procedures due to
      the symmetrical disposition of the anatomy. Thus, handedness could influence the
      performance of these operations. The two of us (L.M.O.) and (J.M.B.), a right
      handed and a left-handed surgeon, respectively, placed the instruments in reverse
      mode from that used in orthotopic patients. The right-handed surgeon felt more
      impairment when dissecting with his left hand and decided to cross the
      instruments within the abdomen. The left-handed surgeon was able to alternate the
      performance of the dissection maneuvers between the right and left hands.
      Surgical procedures are apparently designed for right-handed surgeons and can be
      approached by the left-handed in alternative ways. In fact, the accommodation of
      laparoscopic cholecystectomy to left-handedness has been described in the
      literature. The rare opportunity to operate in a symmetrical way allows the right
      handed surgeon to understand the absence of comfort and ergonomy often
      experienced by left-handed colleagues.

PMID- 14959745
TI  - Hand-assisted advanced laparoscopic procedures--placement of the hand assist
      device is essential.

PMID- 14959746
TI  - Letter: In-line vs pistol-grip handles in a laparoscopic simulator.

PMID- 14959747
TI  - State variation in insurance laws a major driver of employers' self-insurance
      decisions.

PMID- 14959748
TI  - Perfecting the dual-hemostat port-closure technique.

PMID- 14959749
TI  - Stability of serum and plasma ascorbic acid.

PMID- 14959751
TI  - [The vaccinal hypothesis: towards a critical and anthropological approach to a
      historical phenomenon].
AB  - The article calls attention to the complexity of immunization by vaccine, from a
      perspective that combines the biological and social sciences and takes a critical
      view of current interpretations on the history of vaccination, whether negative
      or triumphalist. An anthropological look at vaccines and vaccination reveals the
      multiple historical and geographical facets of what appears to be a unique
      phenomenon, while also prompting questions about the kaleidoscopic unity of human
      practices. There is no single history of vaccination but a history of vaccines
      that have been used in different periods and countries. One consequence of this
      approach is that the concept of public resistance to immunization campaigns is
      replaced by acceptability, which suggests that selecting the procedures to employ
      when immunizing a given population is a hypothesis that should be evaluated based
      on history.

PMID- 14959750
TI  - [Proximal and distal ruptures of the biceps brachii tendon].
AB  - Proximal ruptures. Ruptures of the long head of the M. biceps humeri are commonly
      caused by degenerative changes within the tendon. Non-operative treatment gives
      good results, the loss of power regarding elbow flexion and supination amounts to
      only 8-21%. Refixation may be indicated for cosmetic reasons and offers a small
      but evident improvement of flexion and supination power. Deformity of the slipped
      muscle can be corrected effectively. Residual complaints after conservative
      treatment often result from associated subacromial problems. Distal ruptures.
      Ruptures of the distal tendon should be treated operatively. The loss of power
      after conservative treatment is evident (30-40% for flexion, >50% for
      supination). Extra-anatomical tenodesis to the brachialis muscle or anatomical
      fixation to the radial tuberosity can be applied. Flexion power and cosmesis can
      be addressed by both techniques. If supination strength is to be restored, the
      tendon has to be fixed anatomically. Preparation of the tuberosity bears the risk
      of heterotopic ossification or nerve damage. Mini-open techniques, using only a
      limited anterior approach, may decrease risks.

PMID- 14959752
TI  - Use of progesterone to reduce preterm birth.
AB  - Preterm birth affects 12% of all births in the United States. Recent studies
      support the hypothesis that progesterone supplementation reduces preterm birth in
      a select group of women (ie, those with a prior spontaneous birth at <37 weeks of
      gestation). Despite the apparent benefits of progesterone in this high-risk
      population, the ideal progesterone formulation is unknown. The American College
      of Obstetricians and Gynecologists Committee on Obstetric Practice believes that
      further studies are needed to evaluate the use of progesterone in patients with
      other high-risk obstetric factors, such as multiple gestations, short cervical
      length, or positive test results for cervicovaginal fetal fibronectin. When
      progesterone is used, it is important to restrict its use only to women with a
      documented history of a previous spontaneous birth at less than 37 weeks of
      gestation because unresolved issues remain, such as optimal route of drug
      delivery and long-term safety of the drug.

PMID- 14959753
TI  - SARS returns to China.

PMID- 14959754
TI  - Laboratory-acquired SARS raises worries on biosafety.

PMID- 14959755
TI  - Blood transfusion linked to vCJD death.

PMID- 14959756
TI  - SARS: an amalgam of avian and mammalian viruses?

PMID- 14959757
TI  - USA faces chronic vaccine shortages.

PMID- 14959758
TI  - Bush hesistates on HIV pledge.

PMID- 14959759
TI  - Marburg miner mystery.

PMID- 14959760
TI  - Call to rescind price boosting of ritonavir.

PMID- 14959762
TI  - AACE Launches a new section of cancer communication.

PMID- 14959761
TI  - A complex anterior mediastinal mass: demonstration of pericardial haemangioma by
      dynamic MRI (2003:10b).

PMID- 14959763
TI  - [Overview of an anthropology of the vaccine: a look at the ethics of a
      humanitarian practice].
AB  - Two interrelated universal practices, humanitarian medicine and immunization,
      pose certain ethical problems. To shed light on the matter, we present some
      historical reference points indispensable to an understanding of contemporary
      vaccination programs, focusing especially on certain anthropological issues posed
      by this practice as far as representations of the body and of health within
      populations. Two examples of humanitarian vaccination practices, one used among
      an autochthonous population and the other among young people on the street, serve
      to illustrate some thoughts on management of the body and on the resistance
      displayed by these groups. We then propose paths to follow in re-examining the
      ethics of vaccination.

PMID- 14959764
TI  - [Producing an immunizing agent: images from the production of a yellow fever
      vaccine].
AB  - Through analysis of a set of photographs on the production of a yellow fever
      vaccine in Brazil, the article discusses the use of images as a research source
      in the history of medicine and public health. part of a historical archive
      belonging to the Fundacao Rockefeller, stored at the Casa de Oswaldo Cruz/Fiocruz
      the photographs were produced between the 1930s and 1940s by the Fundacao
      Rockefeller and Brazil's National Yellow Fever Service, institutions then
      responsible for research and control of the disease in Brazil. The article raises
      some questions generally posed by those who employ images as sources or objects
      of interpretation in the production of historical knowledge, and also points to
      the theoretical, conceptual, and methodological aspects involved in this process
      of analyzing images. It goes on to interpret these photographs from the beginning
      of the yellow fever vaccine.

PMID- 14959765
TI  - [Twentieth-century psychiatry in Western Europe and the USA - an attempt at a
      retrospection].
AB  - The article analyzes various areas of twentieth-century psychiatry: (1) a number
      of ideas whose roots date to the second half of the 19th century, including the
      ideas of biological psychiatry, constitutional psychiatry and behavioural
      therapy; (2) the emergence of a modern paradigm of mental disease and the
      contribution made to that field by Kraepaelin and Bleuler; (3) attempts to find
      new effective solutions, especially with regard ot biological therapy; (4) an
      overview of the problems and dilemmas of contemporary psychiatry. Special
      emphasis has been put in the article on the stages and dimensions of the socalled
      "psychopharmacological revolution" and the history fo the development of various
      groups of psychiatric drugs (chlorpromazine and the first psychiatric drugs,
      soporifics and sedatives, antidepressants). The author makes an attempt to point
      out the fundamental dilemmas of contemporary psychiatry, especially the dangers
      it faces from other branches of medicine and non-medical disciplines, as well as
      from mass culture and commercialization.

PMID- 14959766
TI  - Snow on the equator: Reflections on the CAM wars.

PMID- 14959767
TI  - European bat lyssaviruses: an emerging zoonosis.
AB  - In Europe, two bat lyssaviruses referred to as European bat lyssaviruses (EBLVs)
      types 1 and 2 (genotypes 5 and 6 respectively) which are closely related to
      classical rabies virus are responsible for an emerging zoonosis. EBLVs are host
      restricted to bats, and have been known to infect not only their primary hosts
      but also in rare circumstances, induce spillover infections to terrestrial
      mammals including domestic livestock, wildlife and man. Although spillover
      infections have occurred, there has been no evidence that the virus adapted to a
      new host. Since 1977, four human deaths from EBLVs have been reported. None of
      them had a record of prophylactic rabies immunization. Only fragmentary data
      exist about the effectiveness of current vaccines in cross-protection against
      EBLVs. It is clear that EBLV in bats cannot be eliminated using conventional
      strategies similar to the control programmes based on vaccine baits used for fox
      rabies in Europe during the 1980s. Due to the protected status of bats in Europe,
      our knowledge of EBLV prevalence and epidemiology is limited. It is possible that
      EBLV is under-reported and that the recorded cases of EBLV represent only a small
      proportion of the actual number of infected bats. For this reason, any
      interaction between man and bats in Europe must be considered as a possible
      exposure. Human exposure through biting incidents, especially unprovoked attacks,
      should be treated immediately with rabies post-exposure treatment and the bat,
      where possible, retained for laboratory analysis. Preventative measures include
      educating all bat handlers of the risks posed by rabies-infected animals and
      advising them to be immunized. This review provides a brief history of EBLVs,
      their distribution in host species and the public health risks.

PMID- 14959768
TI  - Fresh garlic: a possible vehicle for Salmonella Virchow.
AB  - A sustained increase in Salmonella enterica serovar Virchow notifications in
      South Eastern Australia between September 1997 and May 1998 instigated a case
      control study and environmental investigations. Cases were defined as having
      locally acquired culture-confirmed S. Virchow phage-type 8 infection and
      diarrhoeal disease. Matched controls were selected by progressive digit dialling
      based on cases' telephone numbers. An exposure and food history questionnaire was
      administered by telephone. Phage typing and pulse field gel electrophoresis were
      performed on case and environmental isolates. Thirty-two notifications of S.
      Virchow infection met the case definition, 37% reported bloody diarrhoea and S.
      Virchow was isolated from blood in 13% of cases. Twelve patients were admitted to
      hospital and one died. Fresh garlic (OR 4.1, 95% CI 1.3-12.8) and semi-dried
      tomatoes (OR 12.6, 95% CI 1.5-103.1) were associated with these cases. The
      associations remained significant after adjusting for sex and age. S. Virchow (PT
      8) was cultured from two brands of semi-dried tomatoes associated with cases in
      two different states. We provide sufficient evidence for semi-dried tomatoes and
      fresh garlic to be considered as potential risk foods in future Salmonella
      outbreak investigations.

PMID- 14959769
TI  - An outbreak of pertussis among young Israeli soldiers.
AB  - In winter 2001, an outbreak of pertussis involving an estimated 75 people
      occurred among soldiers serving in an infantry regiment of the Israeli Defense
      Forces (IDF). Nasopharyngeal swabs were obtained from patients and contacts for
      culture and PCR. Serum samples were obtained and assayed by ELISA for the
      presence of IgA, IgM and IgG antibodies to a lysate antigen of Bordetella
      pertussis. The calculated attack rate was 21% based on clinical signs alone
      (cough lasting 30 days or longer) and 9.5% based on clinical signs with
      laboratory confirmation (by PCR, IgA or IgM). A high carriage rate was observed;
      20% of the asymptomatic and previously symptomatic subjects were PCR-positive for
      B. pertussis. These findings emphasize the importance of B. pertussis as a
      causative agent of epidemic respiratory infections in young adults and reveal the
      occurrence of a significant proportion of pertussis transient carriers during an
      outbreak of the disease.

PMID- 14959770
TI  - Outbreaks of Escherichia coli O157 infections at multiple county agricultural
      fairs: a hazard of mixing cattle, concession stands and children.
AB  - Escherichia coli O157 infections cause an estimated 60 deaths and 73 000
      illnesses annually in the United States. A marked summer peak in incidence is
      largely unexplained. We investigated an outbreak of E. coli O157 infections at an
      agricultural fair in Ohio and implicated consumption of beverages made with
      fairground water and sold by a geographically localized group of vendors who were
      all on the same branch of the fairground water distribution system. To examine
      county fair attendance as a risk factor for infection, we conducted two further
      epidemiological studies. In the first, we enhanced surveillance for E. coli O157
      infections in 15 Northeast Ohio counties during the 2000 agricultural fair season
      and showed increased risk of E. coli O157 infection among fair attendees. In the
      second study, we examined Ohio Public Health Laboratory Information Service
      (PHLIS) data for 1999 using a time-varying covariate proportional hazards model
      and demonstrated an association between agricultural fairs and E. coli O157
      infections, by county. Agricultural fair attendance is a risk factor for E. coli
      O157 infection in the United States and may contribute to the summer peak in
      incidence. Measures are needed to reduce transmission of enteric pathogens at
      agricultural fairs.

PMID- 14959771
TI  - Investigation of an outbreak of Escherichia coli O157 infection caused by
      environmental exposure at a scout camp.
AB  - In May 2000 a scout camp was held on an agricultural showground in New Deer,
      Aberdeenshire. There were 337 campers at the event, comprising 233 cubs, scouts,
      and venture scouts, and 104 adults. The event was abandoned early because of
      heavy rainfall. Twenty campers who became ill between 28 May and 3 June were
      confirmed as having E. coli O157 infection. Preliminary investigation did not
      suggest a food vehicle but did indicate environmental exposure at the camp as a
      risk factor. Subsequent investigations supported the hypothesis that transmission
      of E. coli O157 was from the environment to cases by contaminated hands, either
      directly from hand to mouth, or via food. As a result of the investigation the
      Aberdeenshire Council and the Scout Association jointly prepared interim
      guidelines to reduce the risk of E. coli O157 infection at scout camps.

PMID- 14959772
TI  - Tuberculosis is still a major cause of cervical lymphadenopathies in adults from
      developing countries.
AB  - To establish the frequency of infectious aetiology in Mexican adult patients with
      cervical lymphadenopathies (CLAs), 87 consecutive patients with enlarged cervical
      lymphatic nodes, HIV negative and without anti-tuberculous treatment, were
      selected from a tertiary-level speciality concentration hospital.
      Histopathological studies, investigation of acid-fast bacilli, cultures in
      Lowenstein Jensen and Mycobacterium growth indicator tube (MGIT) media, and in
      house polymerase chain reaction (PCR) with IS6110-based primers for Mycobacterium
      tuberculosis complex were performed in resected lymphatic nodes. Non-infectious
      aetiology corresponded to 45 cases (52 %). Tuberculosis was suspected in 42 cases
      (48%) by histology and confirmed positive results were obtained by staining in 8
      (19%), by culture in 23 (55%), and by PCR in 34 (81 %) patients. All were
      confirmed after therapeutic success. In addition to the epidemiological
      transition process occurring in Mexico, tuberculosis remains an important cause
      of CLA. Histopathology with confirmatory studies including PCR can detect
      tuberculous aetiology.

PMID- 14959773
TI  - Effect of clinical and socio-economic factors on the rate of clustering of
      Mycobacterium tuberculosis clinical isolates in Elche (Spain).
AB  - We studied the association that exists between the epidemiological type
      clustering of isolates of Mycobacterium tuberculosis and certain clinical,
      epidemiological and socio-economic characteristics of tuberculosis patients in
      the Elche health district of Spain. A total of 144 patients diagnosed between
      1993 and 1999 and whose isolates had been genotyped by IS6110-RFLP in an earlier
      study were included. Multivariate analysis showed that the independent variables
      associated with clustering of strain types were: age (1-25 years, OR 2.92, 95% CI
      0.83 10.3), a high percentage of infection in the first circle of contacts (OR
      2.89, 95% CI 0.96-8.68), urban dwelling (OR 2.12. 95% CI 0.73-6.2), use of
      bronchoscopy to obtain samples (OR 16.3, 95% CI 2.3-11.5) and working contact
      with many people (OR 2.81, 95% CI 0.94-8.3). These data contribute to a better
      understanding of the epidemiology of tuberculosis and improved systems of
      control.

PMID- 14959774
TI  - The seroepidemiology and transmission dynamics of varicella in Australia.
AB  - To enhance our understanding of the epidemiology and transmission dynamics of
      varicella in the pre-vaccine era we performed a serosurvey using
      opportunistically collected sera submitted to diagnostic laboratories across
      Australia during 1997-1999. A representative sample by state and sex of 2027 sera
      from persons aged 1-49 years was tested using an enzyme immunoassay method. The
      average age of infection and age-specific forces of infection (the probability
      that a susceptible individual acquires infection) were calculated using published
      methodologies. Seropositivity increased with age, with 83% of sera positive by
      ages 10-14 years. The highest force of infection was in the 5-9 years age group
      (0.195 per susceptible year) followed by the 0-4 years age group (0.139 per
      susceptible year) and the average age of infection was 8.15 years. These results
      provide valuable baseline information to measure the impact of vaccination and
      indicate that vaccination should be aimed at children less than 5 years of age,
      although further modelling using the serosurvey data is warranted.

PMID- 14959775
TI  - Community-based estimates of incidence and risk factors for childhood pneumonia
      in Western Sydney.
AB  - The aim was to estimate the community incidence and risk factors for all-cause
      pneumonia in children in Western Sydney, Australia. A cross-sectional randomized
      computer-assisted telephone interview was conducted in July 2000, in Western
      Sydney. Parents of 2020 children aged between 5 and 14 years were interviewed
      about their child's respiratory health since birth. No verification of reported
      diagnosis was available. Logistic regression analysis was used to determine risk
      factors for pneumonia. A lifetime diagnosis of pneumonia was reported in 137/2020
      (68%) children, giving an estimated incidence in the study sample of 7.6/1000
      person-years. Radiological confirmation was reported in 85% (117/137).
      Hospitalization was reported in 41% (56/137) and antibiotic therapy in 93%
      (127/137) of cases. Using logistic regression modelling, statistically
      significant associations with pneumonia were a reported history of either asthma,
      bronchitis or other lung problems and health problems affecting other systems. In
      most cases, the diagnosis of asthma preceded the diagnosis of pneumonia. The
      community incidence of all causes of pneumonia is not well enumerated, either in
      adults or in children. This study provides community-based incidence data. The
      incidence of hospitalization for pneumonia in this study is comparable to
      estimates from studies in comparable populations, suggesting that retrospective
      parental report for memorable events is likely to be valid. We found a
      relationship between pneumonia and childhood respiratory diseases such as asthma,
      which has implications for targeted vaccination strategies.

PMID- 14959776
TI  - Community-acquired Legionnaires' disease in Nottingham--too many cases?
AB  - The aim of this study was to compare the incidence of community-acquired
      Legionnaires' Disease in Nottingham with England and Wales and to explore reasons
      for any difference observed. Based on data from the National Surveillance Scheme
      for Legionnaires' Disease (1980-1999), the rate of infection in England and Wales
      was 1.3 per million/year compared with 6.6 per million/ year in Nottingham.
      Domestic water samples were obtained from 41 (95%) of 43 Nottingham cases between
      1997 and 2000. In 16 (39%) cases, Legionella sp. were cultured in significant
      quantities. Proximity to a cooling tower was examined using a 1:4 case-controlled
      analysis. No significant difference in the mean distance between place of
      residence to the nearest cooling tower was noted (cases 2.7 km vs. controls 2.3
      km; P = 0.5). These data suggest that Nottingham does have a higher rate of
      legionella infection compared to national figures and that home water systems are
      a source.

PMID- 14959777
TI  - A large infantile gastroenteritis outbreak in Albania caused by multiple emerging
      rotavirus genotypes.
AB  - By the end of December 2000, the epidemiological system 'Alert' of the Public
      Health Institute in Tirane reported an outbreak of acute gastroenteritis. The
      outbreak involved children in Tirane and in the rural area. In total, 2722
      children were seen in Tirane Hospital and 982 (56.4%) were treated for acute
      gastroenteritis. The age group with the highest morbidity was 0-5 years (89.7%),
      followed by the 6-9 (6.2%) and 10-15 years age groups (4.1%). The distribution of
      acute gastroenteritis cases, which occurred along the same water distribution
      system, suggests a waterborne origin. The nucleic acid amplification confirmed
      the co-circulation of different genotypes of rotavirus, mainly P[8]G9 and P[8]G3,
      responsible for the outbreak. Other enteric viruses such as astrovirus serotype
      1, adenovirus and Norovirus, genogroups I and II were detected. Co-infections
      with different rotavirus genotypes and even with different enteric viruses were
      detected in several samples.

PMID- 14959778
TI  - Natural history of chronic viral hepatitis in southern Italy: epidemiological
      changes since the introduction of the anti-HCV test.
AB  - We investigated whether there are differences between the natural history of B
      and C chronic hepatitis in a southern Italian population, and whether the chronic
      viral hepatitis population was modified by the introduction of the anti-HCV test
      in 1989. We examined clinical charts of 1120 patients consecutively admitted to
      our division from January 1979 to December 1998 with the histological diagnosis
      of chronic viral hepatitis (304 from 1979 to 1988; 816 from 1989 to 1998). We
      found significant differences only in age at diagnosis (higher in the second
      decade, P = 0.001), and in aetiology (HBV decreased in the second decade, P <
      0.0001). We were able to follow up 449 patients for 2-20 years (311 with HCV and
      138 with HBV infection), and found that chronic HCV evolved to cirrhosis more
      frequently than did chronic HBV; but in both types time to development of
      cirrhosis and the incidence of death were similar. Our data confirm that a higher
      onset age of HBV and of HCV is frequently observed in those subjects who have a
      faster disease progression.

PMID- 14959779
TI  - The relationship between HIV seroconversion illness, HIV test interval and time
      to AIDS in a seroconverter cohort.
AB  - Seroconversion illness is known to be associated with more rapid HIV disease
      progression. However, symptoms are often subjective and prone to recall bias. We
      describe symptoms reported as seroconversion illness and examine the relationship
      between illness, HIV test interval (time between antibody-negative and anibody
      positive test dates) and the effect of both on time to AIDS from seroconversion.
      We used a Cox model, adjusting for age, sex, exposure group and year of estimated
      seroconversion. Of 1820 individuals, information on seroconversion illness was
      available for 1244 of whom 423 (34%) reported symptomatic seroconversion. Persons
      with a short test interval (< or = 2 months) were significantly more likely to
      report an illness than people with a longer interval (OR 6.76, 95% CI 4.75-9.62).
      Time to AIDS was significantly faster (P = 0.01) in those with a short test
      interval. The HIV test interval is a useful replacement for information on
      seroconversion illness in studies of HIV disease progression.

PMID- 14959780
TI  - Human herpesvirus-8 antibodies and DNA in HIV-1 infected patients in South
      Africa.
AB  - HIV-infected individuals with high levels of IgG antibodies against human
      herpesvirus-8 (HHV-8) are at increased risk of developing Kaposi's sarcoma. The
      aim of this study was to measure the association between HHV-8 viraemia and IgG
      antibody responses (by immunofluorescence) in a group of 201 HIV-infected
      individuals attending outpatient clinics, 91 in-patients with AIDS and 87 HIV
      infected patients admitted with Kaposi's sarcoma. Compared to HIV-infected
      outpatients, the adjusted odds ratio in relation to Kaposi's sarcoma was 15.4
      (95% CI 4.4-54.2) in those with viraemia, 25.1 (95% CI 6.6-95.6) in those with a
      positive immunofluorescent signal and infinity (lower exact CI 33.6) in those
      with a high immunofluorescent signal (all P trend < 0.001). Among those without
      HHV-8 viraemia, 23% were IgG-positive, but only 5.5% had a high immunofluorescent
      signal. In those who were viraemic, 89.1% were IgG-positive, and 28.2% had a high
      immunofluorescent signal, suggesting viraemia is associated with high HHV-8
      immunofluorescence IgG signal.

PMID- 14959781
TI  - Serological responses to Cryptosporidium antigens among users of surface- vs.
      ground-water sources.
AB  - Cryptosporidium oocysts are commonly detected in surface-derived drinking water.
      However, the public health significance of these findings is unclear. This study
      compared serological responses to two Cryptosporidium antigen groups for blood
      donors and college students using chlorinated and filtered river water vs. ground
      water sources. The surface water received agricultural and domestic sewage
      discharges upstream. Participants from the surface-water city had a higher
      relative prevalence (RP) of a serological response to the 15/17-kDa antigen group
      (72.3 vs. 52.4%, RP = 1.36, P < 0.001) and to the 27-kDa antigen group (82.6 vs.
      72.5%, RP = 1.14, P < 0.02). Multivariate logistic regression analysis found that
      the people with a shorter duration of residence or drinking bottled water also
      had a lower seropositivity for each marker. Use of private wells was associated
      with a higher prevalence of response to the 15/17-kDa markers. Seroconversion to
      the 15/17-kDa antigen group was more common in the residents of the city using
      surface water. These findings are consistent with an increased risk of
      Cryptosporidium infection for users of surface-derived drinking water compared
      with users of municipal ground-water-derived drinking water. Users of private
      well water may also have an increased risk of infection.

PMID- 14959782
TI  - Acarological risk of exposure to agents of tick-borne zoonoses in the first
      recognized Italian focus of Lyme borreliosis.
AB  - Acarological risk was calculated as the probability of encountering at least one
      host-seeking Ixodes ricinus tick infected by the pathogen Borrelia burgdorferi
      sensu lato, in 100 m transects in the province of Genoa, Italy. The seasonal
      pattern of I. ricinus was studied using generalized estimating equations (GEE)
      with negative binomial error, to consider overdispersion of tick counts and
      repeated sampling of the same dragging sites from April 1998 to March 1999.
      Prevalence of infection by B. burgdorferi s.l. was evaluated by PCR and
      hybridization with genospecies-specific probes. Acarological risk (R) peaked in
      April (R = 0.2, 95% CI 0.13-0.26) and November (R = 0.29, 95% CI 0.10-0.46).
      Borrelia garinii and B. valaisiana were the most common genospecies at our study
      site suggesting a major role of birds as reservoirs. DNA from Anaplasma
      phagocytophilum, the agent of granulocytic ehrlichiosis in humans and animals,
      was amplified from an adult I. ricinus.

PMID- 14959783
TI  - Risk factors and the prevalence of leptospirosis infection in a rural community
      of Chiapas, Mexico.
AB  - A cross-sectional study was conducted in Mapastepec, a rural community of the
      southern state of Chiapas, Mexico. The overall prevalence of leptospirosis
      infection in 1169 subjects was 37.7% [95% confidence intervals (95% CI) 34.9
      40.5]. The main risk factors related to leptospirosis infection were flooding,
      mainly if subjects had a skin cut or abrasion [odds ratio (OR) 4.2; 95% CI 3.1
      5.7], having domestic animals, either dogs and/or cats (OR 1.3; 95% CI 0.96-1.8)
      or cattle and/or pigs (OR 1.9; 95% CI 1.3-2.7), contact with animal excreta with
      no protection and with a skin cut or abrasion (OR 2.3; 95% CI 1.1-4.6). Those
      subjects with a dengue infection in the previous year had also an excess risk (OR
      1.4; 95% CI 0.9-2.0). Mapastepec is a previously unknown area with high
      endemicity. Specific preventive measures should be adopted to prevent any contact
      with infected animals, and animal immunization should also be implemented. There
      is need of an epidemiological surveillance system to allow proper diagnosis.

PMID- 14959784
TI  - Prognostic factors for the long-term development of ocular lesions in 327
      children with congenital toxoplasmosis.
AB  - The aim of this study was to identify the high-risk factors associated with the
      development of ocular lesions in a large cohort of children with congenital
      toxoplasmosis (CT), irrespective of their gestational age at the time of maternal
      infection. Children were managed according to a standardized protocol and
      monitored for up to 14 years at the Croix-Rousse Hospital, Lyon, France. Cox
      model and a flexible regression, spline-based method were used for the analysis.
      During a median follow-up time of 6 years, 79 of the 327 children (24%) had at
      least one retinochoroidal lesion. No bilateral impairment of visual acuity was
      observed. The risk of a child developing ocular disease was higher not only when
      mothers were infected early during pregnancy, which was expected, but also when
      CT was diagnosed prior to or at the time of birth, when non-ocular manifestations
      were present at baseline and when birth was premature.

PMID- 14959785
TI  - Routes for Campylobacter contamination of poultry meat: epidemiological study
      from hatchery to slaughterhouse.
AB  - From April 1998 to March 2000, 18 broiler flocks were followed from the hatchery
      to the slaughterhouse. Campylobacter was not found in the hatchery, 1-day-old
      chicks or in the rearing house before the arrival of the chicks. The infection of
      broiler flocks increased continuously during the rearing time, with a total of
      seven positive flocks at the end of rearing. Farms with Campylobacter-positive
      broilers were characterized by the circulation of Campylobacter in the
      environment (puddles, dung hill) and on the footwear of the farmer. The
      administration of antibiotics did not significantly reduce Campylobacter
      shedding. With the exception of one flock during rearing and a few flocks in the
      slaughterhouse with a mixed Campylobacter coli-Campylobacter jejuni infection, C.
      jejuni exclusively was found both during rearing and on the carcasses. A
      significant correlation exits between the contamination of the broilers during
      rearing and the carcasses after processing. No slaughterhouse was able to avoid
      contamination of carcasses when status-positive animals were delivered. Moreover,
      six negatively delivered flocks yielded positive carcasses, the result of a
      supplementary contamination, which occurred during transport and slaughtering.

PMID- 14959786
TI  - Antibiotic resistance of Campylobacter in raw retail chickens and imported
      chicken portions.
AB  - Campylobacter isolates from raw retail chickens (n = 434) sampled between 1998
      and 2000 were tested for resistance to 12 antibiotics. Among 208 campylobacters
      tested, more than 90% of isolates were susceptible to 4 out of 9 antibiotics
      (nalidixic acid, erythromycin, chloramphenicol and gentamicin). Most
      campylobacters were resistant to 3 antibiotics and multiple resistance was found
      in 4%. Ciprofloxacin resistance was 11%. Campylobacter contamination (28%) in
      imported chickens (n = 150) was almost half that found in local whole chickens
      (50%), but the resistance of imported isolates (n = 42) was similar to that of
      local campylobacters. Resistance in isolates from imported chicken breasts was
      generally more common, but to only 4 antibiotics. Resistance patterns of chicken
      isolates were compared to human clinical isolates (n = 494), and a greater
      similarity was found between the clinical and local isolates than with imported
      campylobacters. Lower chloramphenicol resistance was found in clinical
      Campylobacter isolates than in those from chicken sources.

PMID- 14959787
TI  - The occurrence and epidemiology of Salmonella in European pig slaughterhouses.
AB  - This study was part of an international research project entitled SALINPORK (FAIR
      CT-950400) initiated in 1996. The objectives were to investigate the occurrence
      of Salmonella in pig slaughterhouses and to identify risk factors associated with
      the contamination of pig carcasses. Data was collected from 12 slaughterhouses in
      five European countries. Isolates were characterized by serotyping, phage typing
      and antimicrobial susceptibility. In one country, no Salmonella was found.
      Salmonella was isolated from 5.3% of 3485 samples of pork and from 13.8% of 3573
      environmental samples from the seven slaughterhouses in the four remaining
      countries. The statistical analyses (multi-level logistic regression) indicated
      that the prevalence was significantly higher during the warmer months and that
      the environmental contamination increased during the day of slaughter. The
      polishing (OR 3.74, 95% CI 1.43-9.78) and pluck removal (OR 3.63, 95% CI 1.66
      7.96) processes were found to contribute significantly to the total carcass
      contamination, the latter especially if the scalding water also was contaminated.
      To reduce carcass contamination, it is recommended to ensure sufficiently high
      temperatures of scalding water (62 degrees C) and appropriate cleaning and
      disinfection of the polishing equipment at least once a day in order to reduce
      the level of carcass contamination and consequently the prevalence of Salmonella
      in pork.

PMID- 14959788
TI  - Aerosol treatment of cystic fibrosis.
AB  - Different aerosol therapies have been employed to treat the underlying cause and
      symptoms of cystic fibrosis (CF) during the past two decades. A summary of the
      main elements of the disease and aerosol treatments employed in clinical care and
      experimental trials are presented. Methods of aerosol generation and
      characterization are reviewed. Suggestions for improving the current treatments
      are provided.

PMID- 14959789
TI  - Polymeric micelles for delivery of poorly water-soluble compounds.
AB  - Amphiphilic polymers assemble into nanoscopic supramolecular core-shell
      structures, termed polymeric micelles, which are under extensive study for drug
      delivery. There are several reasons for this growing interest. Polymeric micelles
      maybe safe for parenteral administration relative to existing solubilizing agents
      (for instance, Cremophor EL), permitting an increase in the dose of potent yet
      toxic and poorly water soluble compounds. Polymeric micelles solubilize important
      poorly water-soluble compounds, such as amphotericin B (AmB), propofol,
      paclitaxel, and photosensitizers. A major factor in drug solubilization is the
      compatibility of a drug and a core of a polymeric micelle. In this context, we
      may consider Pluronics, poly(ethylene glycol) (PEG)-phospholipid conjugates, PEG
      b-poly(ester)s, and PEG-b-poly(L-amino acid)s for drug delivery. Polymeric
      micelles may circulate for prolonged periods in blood, evade host defenses, and
      gradually release drug. Thus, they may show a preferential accumulation at sites
      of disease such as solid tumors. Polymeric micelles inhibit p-glycoprotein at
      drug-resistant tumors, gastrointestinal tract, and blood/brain barrier, perhaps
      providing a way to overcome drug resistance in cancer and increase drug
      absorption from the gut and drug absorption into the brain. Lastly, polymeric
      micelles may reduce the self-aggregation of polyene antibiotics, key membrane
      acting drugs used to combat life-threatening systemic fungal diseases. In this
      way, they may reduce its dose-limiting toxicity without a loss of antifungal
      activity.

PMID- 14959790
TI  - Viperlib: a web library of images for perception.

PMID- 14959791
TI  - Anomalous induction of brightness and surface qualities: a new illusion due to
      radial lines and chromatic rings.
AB  - When a chromatic (eg light-blue) annulus surrounds the central gap of an
      Ehrenstein figure so as to connect the inner ends of the radial lines, a striking
      new lightness effect emerges: the central white disk has both a self-luminous
      quality (brighter than in the regular Ehrenstein figure) and a surface quality
      (dense, paste-like). Self-luminous and surface qualities do not ordinarily appear
      co-extensively: hence, the brightness induction is called anomalous. In
      experiment 1, subjects separately scaled self-luminous and surface properties,
      and in experiment 2, brightness was nulled by physically darkening the central
      gap. Experiments 3 and 4 were designed to evaluate the importance of chromatic
      versus achromatic properties of the annulus; other aspects of the annulus (width
      or the inclusion of a thin black ring inside or outside the chromatic annulus)
      were tested in experiments 5-7. In experiments 8-12, subjects rated the
      brightness of modified Ehrenstein figures varying the radial lines (number,
      length, width, contrast, arrangement). Variation of these parameters generally
      affected brightness enhancement in the Ehrenstein figure and anomalous brightness
      induction in a similar manner, but was stronger for the latter effect. On the
      basis of these results, anomalous brightness induction is attributed to a surface
      induction process triggered by an interaction between illusory brightness
      enhancement (due to the radial lines) and border ownership (due to the blue
      annulus).

PMID- 14959792
TI  - Wagon-wheel illusion under steady illumination: real or illusory?
AB  - Wheels turning in the movies sometimes appear to rotate backwards. This is called
      the wagon-wheel illusion (WWI). The mechanism of this illusion is based on the
      intermittent nature of light in films and other stroboscopic presentations, which
      renders them as a series of snapshots rather than a continuous visual data
      stream. However, there have been claims that this illusion is seen even in
      continuous light, which would suggest that the visual system itself may sample a
      continuous visual data stream. We examined the rate of this putative sampling and
      its variations across individuals while in different psychological states. We
      obtained two results: (i) WWI occurred in stroboscopic lights as expected, (ii)
      WWI was never reported by our subjects under continuous lights, such as sunlight
      and lamps with DC power source. Thus, WWI cannot be taken as evidence for
      discreteness of conscious visual perception.

PMID- 14959793
TI  - Perception of surface reflectance of 3-D geometrical shapes: influence of the
      lighting mode.
AB  - We examined in three experiments whether the perception of surface reflectance in
      3-D geometrical shapes is influenced by the mode of lighting, the level of
      surface reflectance, the number of polyhedral faces, and the regularity of
      polyhedral shape. As stimuli, we used simulations of regular polyhedra in a 2AFC
      constant-stimuli procedure to measure how large variations in the reflectance
      needed to be for observers to be able to tell whether the whole surfaces were
      uniform or non-uniform. In almost all the cases observers were more successful in
      discriminating non-uniform polyhedra in the hemispherical diffuse lighting
      conditions than in the collimated lighting conditions. The different levels of
      reflectance had no effect on the discrimination of non-uniformity. Second, as the
      number of faces of the shape increased, discrimination thresholds became lower,
      indicating that the interpretation of reflectance variations was better when a
      shape had many faces. Finally, the regularity of the shape, such as the central
      symmetry, was not an important factor. These results suggest that the
      interpretation of surface reflectance is more precise when surfaces have less
      variance in relative strengths between the face luminance values; these surfaces
      were the ones obtained under hemispherical diffuse lighting.

PMID- 14959794
TI  - Does interhemispheric competition mediate motion-induced blindness? A
      transcranial magnetic stimulation study.
AB  - Motion-induced blindness (MIB) is a phenomenon, perhaps related to perceptual
      rivalry, where stationary targets disappear and reappear in a cyclic mode when
      viewed against a background (mask) of coherent, apparent 3-D motion. Since MIB
      has recently been shown to share similar temporal properties with binocular
      rivalry, we probed the appearance-disappearance cycle of MIB using unilateral,
      single-pulse transcranial magnetic stimulation (TMS)--a manipulation that has
      previously been shown to influence binocular rivalry. Effects were seen for both
      hemispheres when the timing of TMS was determined prospectively on the basis of a
      given subject's appearance-disappearance cycle, so that it occurred on average
      around 300 ms before the time of perceptual switch. Magnetic stimulation of
      either hemisphere shortened the time to switch from appearance to disappearance
      and vice versa. However, TMS of left posterior parietal cortex more selectively
      shortened the disappearance time of the targets if delivered in phase with the
      disappearance cycle, but lengthened it if TMS was delivered in the appearance
      phase after the perceptual switch. Opposite effects were seen in the right
      hemisphere, although less marked than the left-hemisphere effects. As well as
      sharing temporal characteristics with binocular rivalry, MIB therefore seems to
      share a similar underlying mechanism of interhemispheric modulation.
      Interhemispheric switching may thus provide a common temporal framework for
      uniting the diverse, multilevel phenomena of perceptual rivalry.

PMID- 14959795
TI  - The effect of text orientation, visual meridian, and inter-character spacing on
      word identification in the retinal periphery.
AB  - Previous research has demonstrated that the masking effects of flankers about a
      target in the peripheral retina are not isotropic. Rather, regions of lateral
      interaction are ellipsoid in shape with the major axis oriented radially along a
      meridian through the fovea. This finding leads to the counterintuitive prediction
      that horizontal text positioned to the right of fixation might be read more
      slowly than similarly positioned text oriented diagonally or vertically.
      Similarly, vertically oriented text above fixation might be read more slowly than
      horizontally or diagonally oriented text above fixation. We investigated the
      effect of text orientation and inter-character spacing on word identification in
      the retinal periphery. Text was presented by rapid serial visual presentation.
      Words were centered 3 degrees from fixation along four visual field meridians
      (VM) (right horizontal, upper-right diagonal, vertical, and upper-left diagonal).
      Regardless of VM identification, performance was best for horizontal text,
      declining slightly for orientations between +60 degrees and -60 degrees and
      declining more quickly for acute orientations. A weak effect of VM was observed
      for text with normal inter-character spacing. Performance was best for text
      centered along the horizontal meridian and declined slightly along the other VM.
      Finally, identification rates increased by approximately 33 words min(-1) with
      the addition of one character space between adjacent letters. The word
      recognition processes are very tolerant of text orientation, exhibiting a modest
      decline for orientations within +/- 60 of horizontal regardless of VM.

PMID- 14959796
TI  - Transfer of spatial context from visual to haptic search.
AB  - Under incidental learning conditions, spatial layouts can be acquired implicitly
      and facilitate visual search (contextual-cueing effect). We examined whether the
      contextual-cueing effect is specific to the visual modality or transfers to the
      haptic modality. The participants performed 320 (experiment 1) or 192 (experiment
      2) visual search trials based on a typical contextual-cueing paradigm, followed
      by haptic search trials in which half of the trials had layouts used in the
      previous visual search trials. The visual contextual-cueing effect was obtained
      in the learning phase. More importantly, the effect was transferred from visual
      to haptic searches; there was greater facilitation of haptic search trials when
      the spatial layout was the same as in the previous visual search trials, compared
      with trials in which the spatial layout differed from those in the visual search.
      This suggests the commonality of spatial memory to allocate focused attention in
      both visual and haptic modalities.

PMID- 14959797
TI  - "Seeing things in my head": a synesthete's images for music and notes.
AB  - We explored synesthetic experiences (photisms) elicited by music and notes for
      GS, a 22-year-old female college student, who is a genuine digit synesthete
      (Mills et al 1999 Cognitive Neuropsychology 16 181-191). After extensive
      interviews, we conducted five studies using synthesizer notes in different
      octaves and in different instrument sounds. GS described, drew, or selected her
      photisms from alternatives. The results were: (a) her photisms had shape, color,
      movement, and texture: (b) different instruments had photisms with different
      shapes and families of instruments had similar shapes; (c) low-pitched notes were
      darker and larger than high notes; (d) instrument and pitch affected each other;
      (e) a given note was perceived as darker after a high note than after a low note;
      and (f) GS's drawings of notes became more consistent with repeated trials.
      Theoretical observations are discussed on the basis of these results.

PMID- 14959798
TI  - Response inhibition can affect reaction time to abrupt-onset visual displays.
AB  - Reaction time (RT) to abrupt-onset stimuli has been widely used for more than a
      century to measure the duration of perceptuo-cognitive and motor processes
      [Donders, 1868/1969 Attention and Performance II (1969 Acta Psychologica 30 412
      431)]. A complicating factor with the RT method is that of response withholding,
      or response inhibition (RI). The occurrence of RI (under this or other names) has
      been widely discussed in relation to studies of motor processes but has been
      largely ignored in relation to studies of perceptuo-cognitive processes. We
      demonstrate that RI can be a confounding factor when RT to abrupt-onset displays
      is used to study perceptual and cognitive processes. In experiment 1, new-object
      targets were more accurately detected than old-object targets in an unspeeded
      task, but were responded to more slowly in an RT task. Consistent with an
      interpretation in terms of RI, this pattern of results was dependent on the
      difficulty of target detection. The data of three further experiments also
      support predictions from the RI interpretation. It is suggested that RI may be an
      under-acknowledged factor in RT studies of perceptual and cognitive processes
      with abrupt-onset displays.

PMID- 14959799
TI  - Cross-modal and non-sensory influences on auditory streaming.
AB  - Carlyon et al (2001 Journal of Experimental Psychology: Human Perception and
      Performance 27 115-127) have reported that the buildup of auditory streaming is
      reduced when attention is diverted to a competing auditory stimulus. Here, we
      demonstrate that a reduction in streaming can also be obtained by attention to a
      visual task or by the requirement to count backwards in threes. In all conditions
      participants heard a 13 s sequence of tones, and, during the first 10 s saw a
      sequence of visual stimuli containing three, four, or five targets. The tone
      sequence consisted of twenty repeating triplets in an ABA - ABA ... order, where
      A and B represent tones of two different frequencies. In each sequence, three,
      four, or five tones were amplitude modulated. During the first 10 s of the
      sequence, participants either counted the number of visual targets, counted the
      number of (modulated) auditory targets, or counted backwards in threes from a
      specified number. They then made an auditory-streaming judgment about the last 3
      s of the tone sequence: whether one or two streams were heard. The results showed
      more streaming when participants counted the auditory targets (and hence were
      attending to the tones throughout) than in either the 'visual' or 'counting
      backwards' conditions.

PMID- 14959800
TI  - Gross misperceptions in the perceived trajectories of moving dots.

PMID- 14959801
TI  - Specific reading disability (dyslexia): what have we learned in the past four
      decades?
AB  - We summarize some of the most important findings from research evaluating the
      hypothesized causes of specific reading disability ('dyslexia') over the past
      four decades. After outlining components of reading ability, we discuss manifest
      causes of reading difficulties, in terms of deficiencies in component reading
      skills that might lead to such difficulties. The evidence suggests that
      inadequate facility in word identification due, in most cases, to more basic
      deficits in alphabetic coding is the basic cause of difficulties in learning to
      read. We next discuss hypothesized deficiencies in reading-related cognitive
      abilities as underlying causes of deficiencies in component reading skills. The
      evidence in these areas suggests that, in most cases, phonological skills
      deficiencies associated with phonological coding deficits are the probable causes
      of the disorder rather than visual, semantic, or syntactic deficits, although
      reading difficulties in some children may be associated with general language
      deficits. Hypothesized deficits in general learning abilities (e.g., attention,
      association learning, cross-modal transfer etc.) and low-level sensory deficits
      have weak validity as causal factors in specific reading disability. These
      inferences are, by and large, supported by research evaluating the biological
      foundations of dyslexia. Finally, evidence is presented in support of the idea
      that many poor readers are impaired because of inadequate instruction or other
      experiential factors. This does not mean that biological factors are not
      relevant, because the brain and environment interact to produce the neural
      networks that support reading acquisition. We conclude with a discussion of the
      clinical implications of the research findings, focusing on the need for enhanced
      instruction.

PMID- 14959802
TI  - The psychosocial aspects of children exposed to war: practice and policy
      initiatives.
AB  - The atrocities of war have detrimental effects on the development and mental
      health of children that have been documented since World War II. To date, a
      considerable amount of knowledge about various aspects of this problem has been
      accumulated, including the ways in which trauma impacts child mental health and
      development, as well as intervention techniques, and prevention methods.
      Considering the large populations of civilians that experience the trauma of war,
      it is timely to review existing literature, summarize approaches for helping war
      affected children, and suggest future directions for research and policy.

PMID- 14959803
TI  - Management of child and adolescent eating disorders: the current evidence base
      and future directions.
AB  - Although eating disorders in children and adolescents remain a serious cause of
      morbidity and mortality, the evidence base for effective interventions is
      surprisingly weak. The adult literature is growing steadily, but this is mainly
      with regard to psychological therapies for bulimia nervosa and to some extent in
      the field of pharmacotherapy. This review summarises the recent research
      literature covering management in three areas, namely physical management,
      psychological therapies, and service issues, and identifies prognostic variables.
      Findings from the adult literature are presented where there is good reason to
      believe that these might be applied to younger patients. Evidence-based good
      practice recommendations from published clinical guidelines are also discussed.
      Suggestions for future research are made, focusing on 1) the need for trials of
      psychological therapies in anorexia nervosa, 2) applications of evidence-based
      treatments for adult bulimia nervosa to the treatment of adolescents, and 3)
      clarification of the benefits and costs of different service models.

PMID- 14959804
TI  - Peer relations in childhood.
AB  - We present a developmental model that describes normal peer relations and
      highlights processes that underlie the emergence of problems with peers in
      childhood. We propose that children's relationships with peers begin in the first
      years of life, with stable individual differences and preferences for particular
      peers emerging by three years of age. Social skills that facilitate peer
      relationships consolidate in the preschool years, during which time peer groups
      become structured with respect to friendship groups, gender, and dominance
      relations; some children begin to be rejected by their peers. In later childhood
      some children develop entrenched problems with peer relationships, in terms of
      loneliness, bullying and victimisation. Underlying cognitive and emotional
      processes that facilitate successful peer relationships at all ages are
      identified, and the extent to which peer relations play a causal role in the
      genesis of disorder is evaluated. A review of the evidence suggests that, rather
      than a simple pathway from problematic peer relations to disorder, there is a
      reciprocal relationship between children's problems with peers and their
      psychological problems from infancy to adolescence.

PMID- 14959805
TI  - Assessment of young children's social-emotional development and psychopathology:
      recent advances and recommendations for practice.
AB  - In this paper we have tried to document some of the recent advances in the
      conceptualization and assessment of early-emerging social-emotional and behavior
      problems, competencies, and psychopathology. Considerable evidence documents that
      young children evidence significant psychopathology (cf., Del Carmen & Carter, in
      press; Emde, 1999; Zeanah, 2001; Zeanah et al., 1997). Given the range of new
      assessment measures that have become available over the past 10 years, the field
      of young child mental health is poised for dramatic gains in knowledge. It is
      critical to conduct large-scale, longitudinal, epidemiological studies to inform
      our understanding of the course of psychopathological conditions within the
      context of a normative developmental framework. Multi-method, multi-informant
      assessment approaches are more essential in early childhood due to young
      children's inability to provide self-reports and the embedded nature of
      children's development in their caregiving contexts. Screening large
      representative samples affords the opportunity to ascertain unbiased clinically
      informative sub-samples for methodologically intensive sub-studies. These sub
      studies can address the child's cognitive and linguistic developmental capacities
      as well as utilize observational methods to examine the relational context. This
      approach provides an opportunity to merge dimensional and diagnostic assessments
      and will yield critical information for disentangling continuities and
      discontinuities in normative and atypical development. The assessment methodology
      currently exists to routinely screen very young children for social-emotional and
      behavior problems as well as delays in the acquisition of competencies in
      pediatric settings as well as in early intervention programs. Yet, despite the
      likely long-term benefits and cost-saving potential of early identification and
      intervention services, short-term cost and knowledge barriers currently limit
      widespread implementation. Discussions with pediatricians suggest that one of the
      greatest barriers to screening is the limited availability of mental health
      referral sources. Indeed, very few children who are rated by parents as having
      elevated social-emotional and behavior problems are receiving any behavioral
      health services (Horwitz et al., in press). Unmet mental health needs exist among
      non-referred children in the community as well as among children receiving early
      intervention services for developmental concerns. Documenting the mental health
      needs of young children may promote training of professionals who have the
      competence to treat young children and their families. Moreover, the availability
      of social-emotional and behavior problem assessment tools should increase studies
      that focus on the clinical efficacy and effectiveness of prevention and early
      intervention programs designed to promote positive mental health. Finally,
      although significant progress is occurring in the arena of young child diagnosis,
      a strong case can be made for intervening when young children are exhibiting
      elevations in problem behaviors or delays in the acquisition of competence. This
      is particularly true when children are also experiencing exposure to multiple
      contextual risk factors. It is therefore important to advocate for changes to
      systems that require child diagnosis as a gateway to intervention. As we learn
      more about the precursors or prodromal manifestations of clinical psychopathology
      we will be able to examine the efficacy of earlier targeted preventive
      intervention approaches.

PMID- 14959806
TI  - Autism and pervasive developmental disorders.
AB  - The quantity and quality of research into autism and related conditions have
      increased dramatically in recent years. Consequently we selectively review key
      accomplishments and highlight directions for future research. More consistent
      approaches to diagnosis and more rigorous assessment methods have significantly
      advanced research, although the boundaries of the 'broader phenotype' remain to
      be defined and the validity of Asperger's disorder as a discrete syndrome remains
      controversial. Recent epidemiological studies have shown that Autism Spectrum
      Disorders are common, but there continues to be debate about the causes of the
      increase in the frequency with which autism is diagnosed. Psychological research
      has helped to develop new developmental models for the disorder and there have
      also been significant advances in the molecular genetics of autism and
      understanding of the underlying neurobiological processes. Areas important for
      future research include the study of autism as it first develops, i.e., in
      infants and very young children, and of specific processes (psychological and
      neurobiological) which underlie the disorder. Significant challenges lie ahead in
      evaluating the growing number of treatments for autism and in integrating the
      results of research into treatment and educational settings.

PMID- 14959807
TI  - The effect of learning on ventilatory responses to inspiratory threshold loading
      in COPD.
AB  - BACKGROUND: Progressive threshold loading (PTL) is a common test of respiratory
      muscle endurance. Healthy naive subjects improve endurance with successive
      exposures to PTL by altering their breathing responses, thus necessitating a
      familiarization period before reproducible measures can be obtained. This study
      sought to determine whether a similar "learning effect" is evident in patients
      with COPD, and what the mechanism of any such effect may be. METHODS: Ten
      subjects with COPD (FEV1 34+/-13% predicted) underwent PTL on four occasions (>24
      h apart). During PTL measurements were obtained of breathing pattern and maximum
      threshold pressure (Pthmax) achieved. Maximum inspiratory pressure (PImax) was
      measured on each occasion. RESULTS: Over the four tests PImax improved by 21+/
      16% (SD) (P<0.05) and Pthmax by 32+/-21% (P<0.05) with a plateau in these
      measures achieved by test three. Pthmax/PImax was unchanged, being 61+/-11% at
      test one and 67+/-12% at test four. In contrast to healthy subjects, PTL was not
      associated with increased expiratory time or decreased end-expiratory lung
      volume. CONCLUSIONS: In contrast to PImax and Pthmax, which changed with
      successive tests, a single measure of the ratio Pthmax/PImax may present a useful
      guide to the endurance capacity of the respiratory muscles in patients with COPD.

PMID- 14959808
TI  - A simple pharmacokinetic method to evaluate the pulmonary dose in clinical
      practice--analyses of inhaled sodium cromoglycate.
AB  - When the expected effect of an inhaled drug is not achieved, the cause could be
      poor inhalation technique and consequently a low pulmonary dose. A simple in vivo
      test to evaluate the pulmonary dose would be a benefit. This study evaluates the
      relative and systemic bioavailability following inhalation of nebulized sodium
      cromoglycate (SCG) in healthy subjects. Blood samples were collected during 240
      min and urine was collected in two portions, up to 6 h post-inhalation. Two
      exposures were performed and comparisons based on the quantification of drug in
      plasma and urine by a high-performance liquid chromatography (HPLC) procedure
      were done. In one of the exposures, a pulmonary function test was performed to
      study if an expected effect of increased absorption could be detected. There was
      a good correlation between the two exposures shown in the plasma concentrations,
      but not in the urine analyses. The forced exhaled volume manoeuvres were
      associated with a higher Cmax and plasma concentrations up to 60 min post
      inhalation (P<0.01). This effect was not detected in the urine analyses. We
      conclude that this pharmacokinetic method with inhaled SCG and plasma analyses
      could be used to evaluate individual inhalation technique. The HPLC method used
      was rapid and had adequate sensitivity.

PMID- 14959809
TI  - Community-acquired pneumonia mortality: a potential link to antibiotic
      prescribing trends in general practice.
AB  - BACKGROUND: Community prescribing of antibiotics has decreased substantially in
      the UK in recent years. We examine the association between pneumonia mortality
      and recent changes in community-based antibiotic prescribing for lower
      respiratory tract infections (LRTI). METHODS: Retrospective analysis of
      aggregated data for pneumonia mortality, influenza incidence, and antibiotic
      prescribing for LRTI in England and Wales during 12-week winter periods between
      1993/94 and 1999/2000. RESULTS: Winter antibiotic prescribing for LRTI showed a
      30.0% decline since 1995/96. Over the same period, there was a 50.6% increase in
      winter excess pneumonia mortality adjusted for influenza incidence. Negative
      binomial regression analysis showed that the incidence of influenza alone had a
      significant association with winter pneumonia mortality (P<0.001). The analysis
      also showed the reduction in antibiotic prescribing had a small but significant
      association with mortality (P<0.001), when simultaneously modelling for influenza
      incidence. CONCLUSIONS: Our findings suggest an association between recent
      reductions in antibiotic prescribing for LRTI in general practice and an increase
      in pneumonia mortality in England and Wales. This retrospective study of
      aggregate data represents the first attempt to assess the effect of limiting
      antibiotic prescribing on patient outcomes, and highlights the need to identify
      which patients benefit from antibiotic treatment for LRTI.

PMID- 14959810
TI  - Airway inflammation in patients affected by obstructive sleep apnea syndrome.
AB  - Obstructive sleep apnea syndrome (OSAS) has been shown to be associated to upper
      airway inflammation. The object of the present study was to establish the
      presence of bronchial inflammation in OSAS subjects. In 16 subjects affected by
      OSAS, and in 14 healthy volunteers, airway inflammation was detected by the
      cellular analysis of the induced sputum. OSAS patients, as compared to control
      subjects, showed a higher percentage of neutrophils (66.7+/-18.9 vs. 25.8+/-15.6)
      (P<0.001) and a lower percentage of macrophages (29.4+/-18.4 vs. 70.8+/-15.3)
      (P<0.001). The percentage of eosinophils and lymphocytes were not significantly
      different in the two groups. OSAS subjects show bronchial inflammation
      characterized by a significant increase in neutrophils.

PMID- 14959811
TI  - Body mass index and the risk of asthma in adults.
AB  - Asthma and obesity are both chronic conditions and their prevalences have risen
      in affluent societies. A positive association between asthma and being overweight
      or obese has been reported in children and women, but associations in men are
      less clearly described. The objective of this study was to explore the
      association between body mass index (BMI) and asthma in men and women of diverse
      ethnic and socioeconomic background living in New York State, USA. In this study,
      we analyzed cross-sectional data on 5524 subjects aged 18 years and older who
      were interviewed by telephone in the 1996 and 1997 New York State Behavioral Risk
      Factor Surveillance System. Asthma (doctor-diagnosed), and weight and height were
      self-reported. BMI (kg/m2) was used as a measure of adiposity. Weighted logistic
      regression analysis, with stratification by gender and age, was used to examine
      the relationship between asthma prevalence and BMI, adjusting for race/ethnicity,
      education, health insurance, time since last physical examination, physical
      activity and smoking status. The results showed that the prevalence of asthma was
      4.6% (CI: 3.6-5.5%) among men and 8.1% (CI: 7.1-9.1%) among women. In women, the
      prevalence of asthma was significantly increased in those with a BMI 25 kg/m2 or
      higher (BMI 25-27.5: OR = 1.76, 95% CI: 1.06-2.94; BMI 27.5-29.9: OR = 2.45, 95%
      CI: 1.41-4.25; BMI > or = 30: OR = 2.67, 95% CI: 1.66-4.29) when compared to the
      reference category (BMI: 22-24.9 kg/m2). In men, the prevalence of asthma was
      increased in the lowest weight category, BMI < 22 kg/m2 (OR = 3.05, 95% CI: 1.37
      6.78) and in the highest category, BMI > or = 30 kg/m2 (OR = 2.92, 95% CI: 1.39
      6.14). This U-shaped association persisted when restricting the analysis to men
      who had never smoked and was more pronounced for those between 18 and 49 years of
      age. In conclusion, this cross-sectional study showed that men and women differ
      significantly in the association between BMI and asthma prevalence only with
      respect to the lowest weight category. While women had a monotonic association,
      men showed a U-shaped relationship, indicating that both extremes of weight are
      associated with a higher prevalence of asthma.

PMID- 14959812
TI  - Home mechanical ventilation in Sweden--inequalities within a homogenous health
      care system.
AB  - We examined local differences in prescription pattern of home mechanical
      ventilation (HMV) within the homogenous health care system in Sweden. We used 6
      years prospective data from the national HMV Register covering the entire Swedish
      HMV patient population (more than 1000 patients). The treatment prevalence of HMV
      in Sweden, January 1, 1996 was 6.2/100,000 and January 1, 2002 10.5/100,000 with
      a steady increase each year in all counties. The differences between leading and
      non-leading counties showed a tendency to diminish due to an increasing
      prescription rate in the non-leading counties. During the 6 years, the proportion
      of Pickwickian patients increased significantly in the country as a whole, but
      remained considerably and significantly higher in the leading counties, in spite
      of similar and temporally stable prescription criteria. Even if the evident
      dissimilarities in treatment prevalence may be levelling out, it will most
      probably do so at a level as high as or higher than today's top level of more
      than 20/100,000 since we found that HMV therapy was well founded also in the
      counties with the highest prescription rates and that the prescription rate of
      the non-leading counties was approaching the level of the leading counties.

PMID- 14959813
TI  - Outcome of lung cancer patients with acute respiratory failure requiring
      mechanical ventilation.
AB  - To assess the weaning outcome of lung cancer patients with acute respiratory
      failure (ARF) requiring mechanical ventilation, we retrospectively analyzed the
      database of the respiratory intensive care unit at a university-affiliated
      tertiary care hospital. Charts were reviewed for cancer status, biochemistries
      before respiratory failure, causes of respiratory failure, acute physiology and
      chronic health evaluation (APACHE) III score, ventilatory settings, data recorded
      during spontaneous breathing, duration of ventilator days, and weaning outcome.
      Ninety-five consecutive respiratory failure events in 81 patients were recorded
      from January 1, 1995 through June 30, 1999. Twenty-six episodes ended with
      successful weaning (27.4%). Age, gender, and cancer status did not affect the
      weaning outcome. Serum albumin level, APACHE III score, highest fractional
      inspired O2 (FiO2) and highest positive end-expiratory pressure, organ failure,
      ability to shift to partial ventilatory support, and duration of mechanical
      ventilation could significantly influence the weaning outcome statistically. The
      overall hospital mortality rate was 85.2%. Our results suggested that lung cancer
      patients with ARF will have a better chance to wean if the initial APACHE III
      score was less than 70, use of FiO2 never exceeded 0.6, or less than 2 additional
      organ systems failed during the treatment course.

PMID- 14959814
TI  - Respiratory findings in gun factory workers exposed to solvents.
AB  - OBJECTIVE: Gun factory workers are exposed to many solvents (toluene, acetone,
      butanol, xylene, benzene, trichloroethylene). We investigated whether chronic
      exposure to solvents had adverse effect on respiratory system. MATERIAL AND
      METHODS: The workers were questionnaired by modified Medical Research Council's
      respiratory questionnaire before morning start shift. Then physical examination
      and measurement of pulmonary functions by portable dry rolling spirometer were
      performed. The study group consisted of 1091 gun factory workers. The workers
      were grouped according to their smoking habits (smokers, [exposed n: 353 vs.
      unexposed n: 339] and non-smokers [exposed n: 58 vs. unexposed n: 341]). Asthma
      related symptoms were defined as either definite asthma, probable asthma, and
      possible asthma. RESULTS: In non-smokers, the report of asthma-related symptoms
      was more prevalent in exposed workers than unexposed (39.7% vs. 21.7% OR 2.4[1.3
      4.3], respectively P = 0.003). In smokers, the report of asthma-related symptoms
      was more common in exposed group than unexposed (50.7% vs. 42.5% OR 1.4[1.0-1.9],
      respectively P = 0.03). Logistic regression analysis showed that smoking (OR
      2.8[2.0-3.8] P = 0.00001) and exposure to solvents (OR 1.4[1.1-1.9] P = 0.01)
      were independent risk factors for asthma-related symptoms, after adjusting for
      age. Logistic regression analysis identified that smoking (OR 3.3[2.3-4.6] P =
      0.00001) was independent risk factors for chronic bronchitis. Multiple linear
      regression analysis of lung-function parameters (% forced expiratory volume
      (FEV1), FEV1/forced vital capacity, FEF(25-75)) indicated significant effects of
      smoking. CONCLUSION: Present study indicated significant effects of smoking and
      exposure to solvents, with the smoking effect being the most important on asthma
      related symptoms of gun factory workers.

PMID- 14959815
TI  - Induced sputum CD8+ T-lymphocyte subpopulations in chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Previous studies have shown that the inflammatory response to
      cigarette smoking differs between smokers who develop chronic obstructive
      pulmonary disease (COPD) and those who do not and that the CD8+ T-lymphocytes
      have been identified as a key player in this process. The aim of this study was
      to investigate further the role of CD8+ cells and their subtypes in sputum cells.
      METHODS: Sputum induction was performed in 36 COPD patients, 25 smokers without
      COPD and 10 non-smoking healthy controls. After stimulation of sputum lymphocytes
      with phorbol-myristate-acetate, we used double immunocytochemical methods to
      identify CD4+, CD8+ cells and CD8+ INFgamma or IL4 cells (Tc1,Tc2). RESULTS: COPD
      patients had an increased number of CD8+ cells in sputum as compared with smokers
      without COPD (P = 0.0001) and control subjects (P = 0.001). CD8+-IL4 cells were
      reduced both in COPD and in smokers without COPD compared to controls (P =
      0.0001), while CD8+-IFNgamma cells were significantly reduced only in COPD (P =
      0.001) as compared with controls. A significant (P = 0.02) relationship between
      the CD8+-IL4/CD8+-IFNgamma ratio and FEV1 (% pred) was found only in COPD
      patients. CONCLUSION: These findings suggest that an imbalance both in T
      lymphocyte subpopulation (CD4/CD8) and in CD8+ cell subsets (Tc1/Tc2)
      characterizes the inflammatory responses of smokers with established COPD.

PMID- 14959816
TI  - The use of oxygen in the palliation of breathlessness. A report of the expert
      working group of the Scientific Committee of the Association of Palliative
      Medicine.
AB  - Dyspnoea is a common, distressing symptom and difficult to control with medical
      treatment. The role of oxygen in reducing the severity of the symptoms and
      improving quality of life is still unclear. A working party of the Association of
      Palliative Medicine Science Committee set out to examine the evidence concerning
      the use of oxygen for the palliation of breathlessness in COPD, advanced cancer
      and chronic heart failure and to make recommendations for clinicians working in
      palliative care. There were very few randomised controlled trials available for
      any of these conditions. There was no evidence available for heart failure, very
      little for advanced cancer and although there were a number of trials on the use
      of oxygen in COPD very few, until recently, used reduction of breathlessness as
      an outcome measure. Recommendations are made on the basis of the evidence
      available and expert opinion such as the Royal College of Physicians report on
      the use of domiciliary oxygen. Oxygen use has to be tailored to the individual
      and a formal assessment made of its efficacy for reducing breathlessness and
      improving quality of life for that person [corrected].

PMID- 14959817
TI  - Validation of a chronic obstructive pulmonary disease screening questionnaire for
      population surveys.
AB  - The Confronting Chronic Obstructive Pulmonary Disease (COPD) Survey in North
      America and Europe conducted during 1999-2000 aimed to identify international
      differences in the clinical management of COPD and the patients' perspectives on
      their disease. Our aim was to validate the screening questionnaire used in this
      study in a sample of patients presenting at a respiratory clinic. Interviews were
      conducted at an outpatient clinic of the London Chest Hospital. Of the 136
      patients contacted, 25 refused or were not able to participate. Questionnaire
      data were validated by comparison with medical records and spirometry on 104
      patients. Overall, the questionnaire correctly identified 86.5% of patients with
      a diagnosis of COPD with a chance-corrected agreement (kappa = 0.66, SE 0.098),
      which indicates good agreement between the questionnaire alpha and the medical
      records. The questionnaire had a high sensitivity (92.0%) and specificity (72.4%)
      with respect to the diagnosis of COPD. The screening questionnaire used in The
      Confronting COPD Survey appears to be a valid screening tool to differentiate
      COPD from other respiratory diseases.

PMID- 14959818
TI  - Supplemental oxygen increases arterial stiffness in chronic obstructive pulmonary
      disease.
AB  - STUDY OBJECTIVES: Recently, we demonstrated significantly improved baroreflex
      sensitivity (BRS) and autonomic balance after 31% supplemental oxygen (SuppO2) in
      resting patients with chronic obstructive pulmonary disease (COPD). In order to
      investigate whether peripheral arterial stiffness changes may play a role, we
      evaluated changes in peripheral arterial stiffness and BRS after SuppO2. DESIGN:
      Single blinded crossover design. SETTING: Pulmonary exercise testing laboratory.
      PARTICIPANTS: Seventy subjects with moderate to severe COPD. INTERVENTIONS: We
      measured arterial vascular stiffness using the augmentation index via contour
      analysis of the radial pulse obtained from applanation tonometry. BRS was derived
      using the sequence method before and after treatments with compressed air (CA)
      and 30% SuppO2 in 70 individuals with COPD via a counterbalanced crossover
      design. RESULTS: Paired t-tests indicated significant differences in oxygen
      saturation (SaO2) following SuppO2 when compared to CA (mean 96.0+/-2.0% SuppO2
      versus mean 92.6+/-3.6% CA, P<0.001). BRS was significantly greater following
      SuppO2 compared to CA (mean 3.5+/-2.3 ms/mmHg SuppO2 versus mean 3.1+/-2.1 CA
      ms/mmHg, P<0.03). Vascular stiffness was significantly increased with SuppO2 when
      compared with CA (mean 13.3+/-6.1% SuppO2 versus mean 10.8+/-4.9% CA, P<0.001).
      CONCLUSIONS: Our findings indicate that oxygen supplementation ameliorates BRS by
      changes in vasomotor activity. The amelioration of the BRS into a more normal
      range is a move towards the restoration of more normal physiology.

PMID- 14959819
TI  - Proteomic approaches to antigen discovery.
AB  - Proteomics has been widely applied to develop two-dimensional polyacrylamide gel
      electrophoresis maps and databases, evaluate gene expression profiles under
      different environmental conditions, assess global changes associated with
      specific mutations, and define drug targets of bacterial pathogens. When coupled
      to immunological assays, proteomics may also be used to identify B-cell and T
      cell antigens within complex protein mixtures. This chapter describes the
      proteomic approaches developed by our laboratories to accelerate the antigen
      discovery program for Mycobacterium tuberculosis. As presented or with minor
      modifications, these techniques may be universally applied to other bacterial
      pathogens or used to identify bacterial proteins possessing other immunological
      properties.

PMID- 14959820
TI  - Immunoproteomics.
AB  - Two-dimensional electrophoresis results in an adequate resolution of the proteome
      of microorganisms to allow the detection and identification of specific antigens
      after blotting on membranes and overlaying the protein pattern with patient's
      sera. The complement of all identified antigens presents the immunoproteome of a
      microorganism. All the antigens specific for a microorganism or even for a
      disease are identified by mass spectrometry. For identification, peptide mass
      fingerprinting is used, and post-translational modifications are detected by mass
      spectrometry MS/MS techniques. High-resolution two-dimensional electrophoresis
      and unambiguous identification are prerequisites for reliable results. After
      statistical analysis, the resulting antigens are candidates for diagnosis or
      vaccination and targets for therapy.

PMID- 14959821
TI  - Immunoprecipitation and blotting: the visualization of small amounts of antigens
      using antibodies and lectins.
AB  - The practical problems encountered when purifying and visualizing small amounts
      of antigens from complex cellular and protein mixtures are explored. Practical
      aspects and the relative advantages and disadvantages of immunoprecipitation and
      blotting, the two most commonly used antibody techniques, are discussed. As
      glycosylation of antigens is becoming recognized as an important factor in the
      progress of many diseases, a short section on the use of lectins in precipitation
      and blotting techniques is also included. It is highly likely that a combination
      of precipitation followed by blotting, using either lectin followed by antibodies
      or antibody followed by lectins, will become a valuable tool in characterizing
      cellular antigens and the progression of disease.

PMID- 14959822
TI  - Representational difference analysis of cDNA.
AB  - In this chapter 1 describe the PCR-coupled subtractive hybridization technique of
      representational difference analysis of cDNA (cDNA RDA). cDNA RDA is based on the
      representational difference analysis (RDA) method previously described by
      Lisitsyn et al., and can be used to identify genes whose expression is modified
      between two populations of cells. cDNA RDA is relatively inexpensive to perform
      and requires no prior knowledge of genome sequence data. The combining of PCR
      with a subtractive methodology results in a highly effective and extremely
      sensitive technique with application to very low amounts of starting material.
      The procedure can be divided into three main phases: PCR generation of amplicons
      representative of the starting populations of RNA molecules being compared; the
      two-step subtractive hybridization of these representations, leading to the
      enrichment of amplified fragments of differentially expressed genes and the
      sequential depletion of sequences common to both populations; and the
      purification, cloning, and sequencing of the resulting difference products.

PMID- 14959823
TI  - Microarray data analysis and mining.
AB  - DNA microarray is an innovative technology for obtaining information on gene
      function. Because it is a high-throughput method, computational tools are
      essential in data analysis and mining to extract the knowledge from experimental
      results. Filtering procedures and statistical approaches are frequently combined
      to identify differentially expressed genes. However, obtaining a list of
      differentially expressed genes is only the starting point because an important
      step is the integration of differential expression profiles in a biological
      context, which is a hot topic in data mining. In this chapter an integrated
      approach of filtering and statistical validation to select trustable
      differentially expressed genes is described together with a brief introduction on
      data mining focusing on the classification of co-regulated genes on the basis of
      their biological function.

PMID- 14959824
TI  - Expression cloning.
AB  - Expression cloning involves the selection of specific polypeptides, generated
      from a cDNA or genomic DNA library, based on certain characteristics of the
      expressed proteins, such as antibody or ligand binding, recognition by T-cells,
      function, or complementation of cell defects. Here we describe the detailed
      construction of a genomic, random shear lambda expression library, adsorption of
      anti Escherichia coli antibody from antiserum, the screening of an expression
      library with specific antisera, and the cloning of genes with potential use in
      the diagnosis of infectious disease. This approach has been used successfully by
      our laboratory for the discovery of antigenic components of diagnostics and
      vaccines for several infectious agents including: Mycobacterium tuberculosis,
      Anaplasma phagocytophila (formerly Ehrlichia spp. or E. phagocytophila), Babesia
      microti, Trypanosoma cruzi, Leishmania chagasi, and Chlamydia spp.

PMID- 14959825
TI  - Determination of epitopes by mass spectrometry.
AB  - As a response to an infection, the immune system produces antibodies. The
      determination of the antigenic structure recognized by the antibody through
      epitope mapping provides information about the interaction between antigen and
      antibody for the diagnosis of a disease on a molecular level, for characterizing
      the pathogenesis of the infectious material, and for the development of
      interfering drugs or preventative vaccines. Here we present the determination of
      the fine structure of the linear epitope located on the gp41 protein of the human
      immunodeficiency virus recognized by the monoclonal antibody 2F5. In this
      approach we coupled the antigen SOSgp140 to the antibody 2F5, which was
      covalently linked to an Fc-specific antibody immobilized on cyanogen bromide
      (CNBr)-activated Sepharose beads. Digestion of the antigen with endoproteinase
      LysC resulted in an affinity-bound peptide whose fine structure was characterized
      by digestion with carboxypeptidase Y and aminopeptidase M. All steps of this
      method were monitored by matrix-assisted laser desorption/ionization mass
      spectrometry (MALDI/MS). The epitope recognized by 2F5 was identified to be the
      16-mer peptide with the sequence NEQELLELDKWASLWN.

PMID- 14959826
TI  - Identification of T-cell epitopes using ELISpot and peptide pool arrays.
AB  - Here we describe a method for T-cell epitope identification using a modified
      ELISpot assay that is both simple and efficient. By using a carefully constructed
      array of pools of overlapping peptides spanning the entire antigen sequence to
      stimulate T-cell responses, we are able to detect antigen-specific cytokine
      responses by both CD8+ and CD4+ T cells and identify the specific peptides to
      which the cells are responding. Additionally, by performing magnetic bead
      depletion of either CD8+ or CD4+ cells prior to the assay, we are able to
      determine the phenotype of the responding cells to each of the peptide epitopes
      identified. Use of this method will allow the identification of both CD4+ and
      CD8+ T-cell epitopes without the need for MHC allele-matched reagents and without
      the need for highly specialized instrumentation. By using an array of peptide
      pools, this method also dramatically reduces the number of immune cells required
      to test the entire antigen sequence, often a limiting factor in vaccine testing
      and other studies.

PMID- 14959827
TI  - Virus-like particles: a novel tool for the induction and monitoring of both T
      helper and cytotoxic T-lymphocyte activity.
AB  - T-cells play a crucial role in the control of various viral infections such as
      HIV and herpes viruses. Thus, the development of advanced techniques for the
      stimulation and measurement of both antigen-specific T-helper and CTL responses
      is one of most meaningful objectives in vaccinology. Herein, we present HIV-1
      Pr55gag lipoprotein particles (VLPs) to be a potent antigen for introducing
      epitopes into the MHC-class-I and -II processing and presentation pathway. These
      VLPs can easily be produced in insect cells by using the baculovirus expression
      system. Immunization studies in mice revealed the strong capacity of these VLPs
      to stimulate Gag-specific T-helper-1 cell-biased humoral and cellular immune
      responses. In addition, these VLPs can be used as a stimulator antigen for the
      detection of Gag-specific T-helper and CTL responses, as determined by
      conventional ELISA, ELISpot, FACS, and 51Cr-release assays. These results
      strongly underline the value of VLPs as a stimulator of MHC-class-I and -II
      mediated epitope presentation for preventive, therapeutic, and diagnostic
      purposes.

PMID- 14959828
TI  - Application of single-cell cultures of mouse splenocytes as an assay system to
      analyze the immunomodulatory properties of bacterial components.
AB  - Recently, various bacterial components have been suggested as initiating and
      modulating immune activation, thereby substantially affecting the complex and
      dynamic host/pathogen interactions. Herein, we present a valuable and simple
      methodology for determining the capacity of bacteria as well as defined bacterial
      structures to stimulate cellular effectors of the innate and cognate immune
      system. This assay format is based on the exposure of freshly prepared single
      cell cultures of splenic cells derived from naive mice with the immunogen of
      interest. Herein, the determination of exclusive panels of cytokines by the
      ELISA, ELISpot, and FACS technology will serve as an indicator for the activation
      of defined arms of the immune system. An increased knowledge about microbial
      components with immunomodulatory properties will substantially contribute to a
      more detailed understanding of the dynamic interplay between the host and
      potential pathogens and, based on this knowledge, to the development of novel
      substances for the prevention and therapy of microbial infections.

PMID- 14959829
TI  - High-throughput expression and purification of 6xHis-tagged proteins in a 96-well
      format.
AB  - By using automation and affinity-tag technologies, analysis of the large number
      of ORFs generated by genome-sequencing projects is greatly accelerated. Protocols
      describing culture of E. coli in automation-compatible formats and subsequent
      micro-to large-scale automated purification of 6xHis-tagged proteins are
      presented.

PMID- 14959830
TI  - Production of antigens in Chlamydomonas reinhardtii: green microalgae as a novel
      source of recombinant proteins.
AB  - Recombinant small-scale proteins are produced in a number of systems, from
      bacteria like Escherichia coli, through lower eukaryotes like baker's yeast, up
      to mammalian cell cultures. However, the need for safe and cheap sources of large
      amounts of recombinant proteins for different purposes, including material
      sciences, diagnostics, and, of course, medical therapy, has forced the
      development of alternative production systems. Green microalgae are cheap and
      easily grown and offer a high protein content, which would seem to make them
      ideal hosts for the large-scale sustainable production of recombinant proteins in
      the future. In selected species, recombinant DNA can be introduced into the
      genomes of the nucleus, the chloroplast, and even the mitochondria, and thus the
      system offers both prokaryotic (chloroplast, mitochondria) and eukaryotic
      translation systems for a tailored expression of virtually any protein.

PMID- 14959831
TI  - Codon-optimized genes that enable increased heterologous expression in mammalian
      cells and elicit efficient immune responses in mice after vaccination of naked
      DNA.
AB  - Many of the problems related with mammalian gene expression, such as low
      translation efficiency and mRNA halflife, can be solved by means of a rational
      gene design, based on modern bioinformatics, followed by the de novo generation
      of a synthetic gene. Moreover, high expression rates and prolonged mRNA stability
      are not only crucial for heterologous mammalian expression, but, in particular,
      are important for the generation of effective DNA vaccines. In this chapter we
      show that an optimized synthetic gene encoding the HIV-1 Pr55gag outperforms wild
      type gene driven expression by several orders of magnitude. RNA analysis revealed
      that this positive effect was mostly due to increased mRNA stability of the
      optimized transcripts. Moreover, mice vaccinated with the optimized gag gene
      elicited a much stronger immune response against Pr55gag than the control groups
      immunized with the respective wild-type gene.

PMID- 14959832
TI  - Purification and immunological characterization of recombinant antigens expressed
      in the form of insoluble aggregates (inclusion bodies).
AB  - This chapter describes a straightforward protein purification strategy for the
      specific separation of insoluble recombinant proteins (so-called "inclusion
      bodies") located in the E. coli cytoplasm and their subsequent recovery in form
      of soluble recombinant proteins. Optimization of this technique can overcome in
      some cases the application of tedious and yield-reducing standard protein
      purification procedures. Due to the different behavior of individual recombinant
      proteins during separation, solubilization, and purification, subsequent
      purification steps may be required to obtain recombinant proteins in such a
      purity, that they can be used as antigen components of immunological test
      systems.

PMID- 14959833
TI  - Purification of recombinant proteins with high isoelectric points.
AB  - The use of recombinant antigens is essential for the construction of robust and
      sensitive diagnostic assays. A critical step in the preparation of recombinant
      antigens is protein purification. Purification problems may be very different for
      related structural proteins expressed in the same host or for the same protein
      expressed in different hosts, because the biochemical characteristics of a
      recombinant protein, expressed in a heterologous system, are unique. In this
      chapter we make a brief introduction to protein purification procedures and we
      present a quick purification process suitable for the isolation of recombinant
      protein having high isoelectric points encoding non-conformational epitopes.

PMID- 14959834
TI  - Refolding of inclusion body proteins.
AB  - Genome sequencing projects have led to the identification of an enormous number
      of open reading frames that code for unknown proteins. Elucidation of the
      structure and function of these proteins makes it necessary to produce proteins
      fast, in high yields and at low cost. The recombinant expression of proteins in
      bacterial hosts often results in the formation of inclusion bodies. Here, the
      protein accumulates in large quantities separated from the cellular protein.
      However, the protein is insoluble and inactive. Thus, it is necessary to
      establish efficient refolding protocols. Progress has been made recently in this
      field concerning refolding strategies, the use of low-molecular-weight additives
      as folding enhancers, and the determination of optimum refolding parameters. Here
      we present an overview of the refolding technology and give a standard protocol
      for inclusion body refolding.

PMID- 14959835
TI  - Small-molecule-protein conjugation procedures.
AB  - Small-molecule-protein conjugates are often required to act as immunogeneic
      complexes in the production of both monoclonal and polyclonal antibodies against
      small antigens. When antibodies have been obtained, they (and/or the small
      antigens) need to be labeled to facilitate their use in diagnostic assays. It is
      often impossible or extremely expensive to obtain the required conjugates. This
      chapter therefore discusses the common procedures used to couple small molecules
      to proteins and the analysis of the resulting conjugates. Practical guidance is
      given on the coupling of small molecule carboxyl, hydroxyl, and amine residues to
      amine and sulfhydryl residues on proteins using linkage techniques in which the
      author has extensive experience. Although a comprehensive list and analysis of
      every available linker is not given, the practical advice should enable the
      reader to use any commercially available linker productively to its optimum
      potential.

PMID- 14959836
TI  - Structural characterization of proteins and peptides.
AB  - The primary structure of proteins is nowadays determined by DNA sequencing, and a
      variety of genomes are already known. Nevertheless, protein
      sequencing/identification is still indispensable to analyze the proteins
      expressed in a cell, to identify specific proteins, and to determine
      posttranslational modifications. Proteins of interest are typically available in
      low microgram amounts or even less. The separation method of choice is gel
      electrophoresis, followed by blotting to PVDF membrane for N-terminal sequencing
      or by in-gel digestion to generate peptides that can be separated by HPLC.
      Structural analysis can be done by Edman degradation or mass spectrometry (MS).
      Edman degradation is the older method based on successive removal of N-terminal
      amino acids by chemical methods. Sequencing of a peptide requires many hours, the
      sensitivity is in the range of 2-5 pmol of a purified peptide. Nevertheless,
      Edman degradation is still the workhorse in the lab for routine work such as
      identification of blotted proteins. It is also the method of choice for
      sequencing unknown proteins/ peptides and modified peptides. MS has routinely
      been used with peptides in the range of 100 fmol or even less. In contrast to
      Edman degradation, complex mixtures such as tryptic digests can be analyzed,
      making HPLC separation of peptides unnecessary. MS is a very fast method that can
      be automated. It is the method of choice for sensitive analysis and large-scale
      applications (proteomics). Two different ionization methods are commonly used to
      generate peptide/protein ions for MS analysis. These are MALDI (matrix assisted
      laser desorption and ionization) and ESI (electrospray ionization). They can be
      combined with a variety of mass analyzers (TOF, quadrupole, ion trap). Proteins
      are either identified by searching databases with the masses of proteolytic
      peptides (peptide mass fingerprinting) or using fragmentation data (raw MS/MS
      spectra or sequence tags). This approach requires that the protein is known and
      listed in the database. De novo sequencing by MS of peptides is possible, but
      very time consuming and not a routine application, in contrast to Edman
      degradation. The aim of this chapter is to introduce to basic theory, practical
      applications and limitations of the various methods, to enable the non-expert
      scientist to decide which method is best suited for his project and which kind of
      sample preparation is necessary.

PMID- 14959837
TI  - Determination of kinetic data using surface plasmon resonance biosensors.
AB  - The use of biosensors employing surface plasmon resonance (SPR) provides
      excellent instrumentation for a label-free, real-time investigation of
      biomolecular interactions. A broad range of biological applications including
      antibody-antigen interactions can be analyzed. One major advantage of kinetic
      analysis using SPR-based biosensors is the option of determining separately
      distinct association and dissociation rate constants exceeding the classical
      steady-state analysis of biomolecules. Based on these data new possibilities for
      drug design, characterizing human pathogens, and the development of therapeutic
      antibodies can be achieved. The hardware of commercially available systems is
      described, practical step by step procedures are given, and possibilities and
      limitations of the technology are discussed.

PMID- 14959838
TI  - Affinity measurements of biological molecules by a quartz crystal microbalance
      (QCM) biosensor.
AB  - We present a immunosensing system based on a quartz crystal microbalance (QCM)
      that allows detection and evaluation of a broad range of molecules relevant to
      medicine and biology. Soluble analyte is applied by injection into a flow-through
      chamber where receptor molecules are immobilized, thus enabling real-time
      measurement of the specific intermolecular interactions. This system can be used
      for detection purposes, e.g., screening for antibodies, and for determination of
      affinity constants including affinity evaluation of newly selected or designed
      aptamers, as kd and ka rates can be derived from the sensograms.

PMID- 14959839
TI  - Solid supports in enzyme-linked immunosorbent assay and other solid-phase
      immunoassays.
AB  - Most modern immunoassays involve the use of synthetic solid phases to immobilize
      one of the reactants, often by simple adsorption. These solid-phase immunoassays
      (SPIs) involve ligand-receptor interactions that occur within a reaction volume
      close to the solution/solid-phase interface. As a consequence, the
      immunochemistry/biochemistry of these ligand-receptor interactions differ from
      their counterparts in solution. Nevertheless, mass law equations can be derived
      for measuring the antigen capture of solid-phase antibodies, for determining the
      affinity of solid phases for protein adsorption, and for estimating antibody
      affinity. Many proteins adsorbed on polystyrene or silicone suffer adsorption
      induced conformational changes (ACC) and are partially or largely denatured.
      Alternative methods for immobilizing proteins and virus, while preserving
      antigenicity, may yield only a modest increase in functional reactant
      concentration. Peptides and small recombinant proteins appear to benefit
      especially from nonadsorptive immobilization. Not all solid phases commonly used
      in SPIs have the same properties, the same capacity for reactant immobilization,
      cause the same level of denaturation, or experience the same level of nonspecific
      binding. Empiricism, adherence to a few practical rules of thumb, and avoidance
      of certain "old wives tales" can be valuable in the successful development of
      SPIs.

PMID- 14959840
TI  - Design and preparation of recombinant antigens as diagnostic reagents in solid
      phase immunosorbent assays.
AB  - Analysis of the humoral immune response to infectious diseases has played, and
      will to continue to play, a key role in their diagnosis and immune surveillance.
      Although rapid genome detection methodologies, such as PCR, are beginning to
      replace immune assays for disease diagnosis, they are not suitable for all
      applications, especially the surveillance of the immune status of human
      populations. Here we review the limitations of current conventional tools for
      measuring immune responses and outline principles for the design and production
      of novel diagnostic reagents. Methods for the production of viral diagnostic
      antigens by a variety of recombinant systems are described and their relative
      merits and disadvantages discussed. Protocols for the production of viral
      diagnostic antigens in eukaryotic, insect and mammalian systems are described
      using measles nucleocapsid antigen as a model. Indirect ELISA protocols which can
      differentiate immunoglobulin classes and subclasses are also described. Examples
      of the use of these analyses in research and surveillance are given.

PMID- 14959841
TI  - Basic problems of serological laboratory diagnosis.
AB  - Serological laboratory diagnosis of infectious diseases is inflicted with several
      kinds of basic problems. One difficulty relates to the fact that the serological
      diagnosis of infectious diseases is double indirect: The first indirect aim in
      diagnosing an infectious disease is to identify the microbial agent that caused
      the disease. The second indirect aim is to identify this infectious agent by
      measuring the patient's immune response to the potential agent. Thus, the
      serological test is neither measuring directly disease nor the cause of the
      disease, but the patient's immune system. The latter poses another type of
      problem, because each person's immune system is unique. The immune response to an
      infectious agent is usually of polyclonal nature, and the exact physicochemical
      properties of antibodies are unique for each clone of antibody. The clonal makeup
      and composition and, therefore, the way an individual's immune system sees an
      infectious agent, depends not only on the genetic background of the person but
      also on the individual experience from former encounters with various infectious
      agents. In consequence, the reaction of a patient's serum in an analytical system
      is not precisely predictable. Also, the antigenic makeup of an infectious agent
      is not always foreseeable. Antigenic variations leading to different serotypes is
      a quite common phenomenon. Altogether, these biological problems lead to
      complexities in selecting the appropriate tests and strategies for testing, in
      interpreting the results, and in standardizing serological test systems. For that
      reason, a close collaboration of the laboratory with the clinic is mandatory to
      avoid erroneous conclusions from serological test results, which might lead to
      wrong decisions in patient care.

PMID- 14959842
TI  - Molecular diagnostics resources on the Internet.
AB  - Busy diagnosticians need to know what is useful, and what is dross, when dealing
      with the internet. From the comprehensive array of resources that characterizes
      the offerings available via the world wide web and email correspondence, in
      particular, this chapter seeks to identify the most useful tools for the
      diagnostics laboratory. With rapid communications and fast internet consultations
      only a few keystrokes away, there really is no point in wasting time on fruitless
      searches when professionals are so accessible. But accessibility carries the
      weight of responsibility as well, and communications must be engaged with a fair
      modicum of civility and common courtesy. Responsibility is a crucially important
      component of public or semiprivate communication in terms of your own identity,
      and that of the organization that you represent. Recognition of the relative
      vulnerability of individual machines to the worldwide disseminated computer
      viruses, worms, or trojan horses currently abounding, for example, is perhaps the
      most important step in your approach to security issues, but this recognition
      must go hand in hand with institutional steps to protect the organization of
      which you are a part. Organizational tools that serve the diagnostician well in
      the laboratory can also be mobilized in the aid of communications through the
      net, and always that harbinger of understanding, common sense, should prevail in
      one's dealings both with machines, and the people who are communicating either
      directly or indirectly through them.

PMID- 14959843
TI  - Cloning single-chain antibody fragments (scFv) from hybridoma cells.
AB  - Despite the availability of antibody libraries for the selection of receptor
      molecules, the large number of established and well-characterized hybridoma lines
      still represent a useful source for recombinant antibody genes. This protocol
      describes the PCR amplification, cloning, and a small-scale expression test for
      the generation of scFv fragments from hybridoma cell lines. Particular emphasis
      was placed on frequently observed problems and pitfalls of this method.

PMID- 14959844
TI  - Cross-talk between retinoic acid and STAT3 signaling pathways in acute
      promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) is a form of acute myelogenous leukemia
      characterized by chromosomal alterations involving the retinoic acid receptor
      alpha (RARalpha) gene that generate unique chimeric proteins (N-RARalpha) and by
      clinical responsiveness to all-trans-retinoic acid (ATRA) treatment. APL cells
      are notable for differentiation block and resistance to apoptosis. While
      increasing evidence suggests that N-RARalpha fusion proteins interfere with
      normal RARalpha transcription function at retinoic acid response elements (RAREs)
      resulting in inhibition of normal myeloid differentiation, the mechanism for
      apoptosis resistance remains unexplained. Recently, we and others have reported
      that APL-fusion proteins can augment STAT3 transcriptional activity. Constitutive
      STAT3 activation has been observed in a number of hematopoietic and non
      hematopoietic malignancies where it contributes to apoptosis resistance. In this
      review, we summarize a series of recent observations concerning cross talk
      between the retinoic acid and STAT3 signaling pathways in APL cells. These
      findings support the hypothesis that apoptosis resistance in APL may be mediated
      through the effects of APL fusion proteins on STAT3 signaling and suggest that
      targeting of STAT3 may be a useful adjunctive treatment strategy in APL.

PMID- 14959845
TI  - Dendritic cell-based immunotherapy in multiple myeloma.
AB  - Most patients with multiple myeloma (MM) cannot be cured with currently available
      therapies. Although complete remission could be achieved in about 50% of newly
      diagnosed patients with high-dose chemotherapy and tandem transplantation,
      relapses of the underlying disease occur frequently. To realize long-term disease
      free survival, it will be necessary to develop complementary therapies that are
      non-cross-resistant with chemotherapy. To this end, immunotherapy aimed at
      inducing or enhancing tumor-specific immunity that may control or eradicate
      remaining tumor cells may be an appealing method. Dendritic cells (DCs) are
      professional antigen-presenting cells and considered the best natural adjuvants
      for immunotherapy in malignancies. Vaccination with tumor antigen-pulsed DCs has
      been shown to be protective and therapeutic in animal tumor models, and induced a
      strong tumor-specific immunity and durable tumor regression in human solid tumors
      and B-cell lymphoma. As a result, clinical trials in various human malignancies
      have been initiated. This review will focus on DC-based immunotherapy in MM. I
      will discuss myeloma antigens and antigen-specific immune responses, the capacity
      of DCs to present myeloma antigens and induce cytotoxic T-cell responses, and
      clinical experience of DC vaccination in myeloma patients.

PMID- 14959846
TI  - Hidden aberrations diagnosed by interphase fluorescence in situ hybridisation and
      spectral karyotyping in childhood acute lymphoblastic leukaemia.
AB  - Acute lymphoblastic leukaemia (ALL) is the most common oncologic disease in
      childhood, accounting for approximately 25% of all paediatric malignancies. Based
      on clinical risk criteria and modern laboratory investigations including
      immunophenotyping, cytogenetics and molecular genetics, patients can be divided
      into prognostic groups and assigned to risk-adjusted treatment protocols. The
      karyotype is an independent prognostic indicator and has for some aberrations
      that are associated with a poor outcome a direct impact on the choice of
      treatment. Cytogenetic analysis in ALL is often hampered by poor chromosome
      morphology, few malignant metaphases, undetectable chromosomal rearrangements due
      to regions of a similar size and banding pattern and sometimes only normal
      metaphases derived from normal cells are found after cell culture. Structural as
      well as numerical aberrations may therefore remain undetected using conventional
      G-banding. The application of modern molecular cytogenetic techniques including a
      broad set of fluorescence in situ hybridisation (FISH) methods and recent
      developments in comparative genomic hybridisation to DNA microarrays, together
      with molecular methods such as Southern blotting and RT-PCR has greatly improved
      the detection rate of genetic changes in ALL. This review emphasises the value of
      increasing the resolving power of the cytogenetic investigation by spectral
      karyotyping (SKY) and interphase FISH in identifying prognostically important and
      novel chromosomal rearrangements as a complement to conventional banding
      analysis. The results of investigations performed on cases with ALL have shown
      that interphase FISH is valuable and in many cases even mandatory for the
      detection of prognostically important genetic abnormalities and should therefore
      consistently be employed in the routine cytogenetic investigations in ALL.
      Likewise, SKY is a valuable tool for the cytogenetic analysis. Thus, the results
      of several different investigations described in this review revealed that SKY
      yielded additional information in 97/157 (62%) cases with chromosomal aberrations
      detected by G-banding, and in 10/66 (15%) cases with normal G-banding.

PMID- 14959847
TI  - The expression pattern of CD56 (N-CAM) in human bone marrow biopsies infiltrated
      by acute leukemia.
AB  - In hematological neoplasms CD56 (N-CAM) is expressed by T/natural killer (NK)
      cell lymphoma, by most neoplastic plasma cells in multiple myeloma and also in a
      subset of acute myelogenous leukemias (AML). In the latter, it is an indicator of
      poor clinical outcome. Most of the data on CD56 expression in acute leukemia have
      been obtained by flow cytometric analysis. Up to now, no systematic analysis of
      the expression pattern of CD56 in formalin fixed paraffin embedded bone marrow
      biopsies of acute leukemias has been performed. We immunohistochemically studied
      the expression of CD56 in a series of 141 bone marrow biopsies fixed in Sublimat
      Mercury II Chloride (SUSA) including 100 cases of AML FAB M0-M7, 11 cases of AML
      not further specified, 3 cases of biphenotypical leukemia, 20 cases of acute
      lymphoblastic leukemia (ALL) and 7 cases of reactive bone marrow biopsies.
      Overall, 14 of 134 (10%) leukemia cases were positive for CD56. Detail analysis
      revealed positivity in 5/13 cases of AML M5 (38%), 3/9 AML M1 (33%), 1/8 AML M0
      (13%), 1/11 AML not specified (9%), 2/31 AML M2 (7%) and 2/26 AML M4 (8%). All
      cases of ALL and biphenotypic leukemias were CD56 negative. The CD56 expression
      in AML M5 was statistically significant (p = 0.003). On paraffin embedded bone
      marrow biopsies CD56 expression occurs in de novo AML with an overall frequency
      of 13%. It is significantly correlated with AML M5, which is positive in 38% of
      the cases. Cases of ALL are consistently CD56 negative.

PMID- 14959848
TI  - Immunological effects of interferon-alpha on chronic myelogenous leukemia.
AB  - Treatment with interferon-alpha is effective for chronic myelogenous leukemia in
      the chronic phase (CML-CP), but the immunological mechanisms of the antileukemic
      effect of this substance are still unclear. The objective of this study was to
      investigate the immunological effects of interferon-alpha in CML patients.
      Markers of cellular activation and apoptosis, natural killer (NK) cell
      cytotoxicity and production of intracellular cytokines (IFN-gamma, IL-2 and IL-4)
      were determined by flow cytometry in the peripheral blood mononuclear cells
      (PBMC) of 26 CML-CP patients before and 3, 6 and 9 months after IFN-alpha
      treatment. The results were correlated with the hematological response. In the
      whole group of patients, INF-alpha use was followed by a significant increase of
      lymphocytes producing IL-2 and IFN-gamma, an increase in NK activity and a
      decrease in the number of CD34+ cells. Out of 26 CML patients, 15 achieved
      hematological remission and 7 achieved partial cytogenetic remission after 9
      months of IFN-alpha treatment. There was an increase in the percentage of
      CD8/FasL+, DR/CD3+, DQ/CD3+, CD34/Fas+, DR/CD56+, CD56/FasL+ cells and of IFN
      gamma- and IL-2-producing lymphocytes and an increase in NK cytotoxicity only in
      the group of patients who achieved complete hematological remission. Our results
      indicate that IFN-alpha use in CML-CP reduces the number of CD34+ cells,
      activates T cells, enhances stem cell apoptotic markers and increases the
      production of intracellular IFN-gamma and IL-2 by lymphocytes. Taken together,
      these results indicate that the therapeutic effect of IFN-alpha in CML-CP is
      mediated at least in part by immunological mechanisms.

PMID- 14959849
TI  - Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin's
      lymphoma receiving CHOP chemotherapy.
AB  - We sought to identify risk factors associated with the time to febrile
      neutropenia in patients with intermediate-grade, non-Hodgkin's lymphoma (NHL) who
      were receiving treatment with CHOP chemotherapy. Data were collected from 12
      community and academic oncology practices participating in the Oncology Practice
      Pattern Study between 1991 and 1999. We reviewed the medical records of 577
      intermediate-grade NHL patients who received initial CHOP chemotherapy and
      evaluated risk factors associated with time to first febrile neutropenic event. A
      febrile neutropenic event was defined as a body temperature of > 100.6 degrees F
      and an ANC nadir < 1000/mm3. A total of 160 patients experienced 224 febrile
      neutropenic events. The risk of febrile neutropenia was significantly associated
      with age > or = 65 years (p = 0.001), cardiovascular disease (p = 0.020), renal
      disease (p = 0.006), baseline hemoglobin < 12 g/dl (p = 0.018), > 80% planned
      average relative dose intensity (ARDI; p = 0.018), and no prophylactic colony
      stimulating factor (CSF) use (p = 0.046). First febrile neutropenic events
      occurred by day 14 of cycle 1 in one-half of patients experiencing febrile
      neutropenia. In multivariate analysis, the risk of febrile neutropenia remained
      significantly associated with age > or = 65 years (HR = 1.65, 95% CI: 1.18-2.32),
      renal disease (HR = 1.91. 95% CI: 1.10-3.30), cardiovascular disease (HR = 1.54,
      95% CI: 1.02-2.33), baseline hemoglobin < 12 g/dl (HR = 1.44, 95% CI: 1.04-2.00),
      > 80% planned CHOP ARDI (HR = 2.41, 95% CI: 1.30-4.47), and no CSF prophylaxis
      (HR = 2.13, 95% CI: 1.20-3.76). Such a model may permit the identification of
      patients at greatest risk of febrile neutropenia and, therefore, candidates for
      the selective prophylactic use of the hematopoietic growth factors.

PMID- 14959850
TI  - Deletion mapping of the long arm of chromosome 6 in peripheral T and NK cell
      lymphomas.
AB  - Deletion of chromosome 6q has frequently been observed in natural killer (NK)
      cell lymphomas. The aim of this study, is to localize the commonly affected
      region in chromosome 6q and to compare the frequency of loss of heterozygosity
      (LOH) between the peripheral T and NK cell lymphomas. Eight cases of peripheral T
      cell lymphomas, not otherwise characterized (PTCL-NOC), and 5 cases of nasal-type
      NK/T cell lymphomas were enrolled for the study. Twelve polymorphic markers
      covering the regions from 6q13 to 6q24, according to the Entrez Database
      (National Center for Biotechnology Information, NIH, Bethesta, MD), were used for
      LOH analysis. Results showed LOH at least one locus on chromosome 6q was observed
      in all cases. Of the informative cases, the overall frequency of LOH for each
      marker ranged from 8.3 to 58.3%. NK/T cell lymphomas showed a higher frequency of
      LOH compared to the PTCL (47.44 +/- 12.39 vs. 30.89 +/- 11.97%). The average
      frequency of LOH was 31.93 +/- 16.04% in stages I + II of the disease, whereas
      the average was 45.78 +/- 4.15% in stages III + IV. The most frequently involved
      regions were at markers D6S434 (5 of 8 informative cases, 62.5%) on chromosome
      6q16.3 in the PTCL, D6S302 (4 of 5 cases, 80%) on chromosome 6q21 and D6S287 on
      6q22.3 (4 of 5 cases, 80%) in the NK/T cell lymphoma. In conclusion, LOH of
      chromosome 6q is more common in nasal-type NK/T cell lymphoma than PTCL. The
      difference between the commonly lost region of chromosome 6q in NK/T cell
      lymphoma and that in PTCL suggests that different tumor suppressor genes are
      involved in the genetic evolution pathway of these two diseases.

PMID- 14959851
TI  - Polymorphisms in the interleukin-10 and interferon gamma genes in Hodgkin
      lymphoma.
AB  - Genetic factors are known to be important in the development of Hodgkin lymphoma
      (HL). Interleukin-10 (IL-10) secretion by both malignant and reactive cells is
      thought to be important in the pathogenesis of HL especially Epstein-Barr virus
      (EBV) positive cases. Polymorphisms of the IL-10 gene have been reported to be
      associated with susceptibility to EBV infection. The cytotoxic response to EBV is
      determined by a Th1 biased immune response which is characterised by interferon
      gamma (IFNgamma) secretion. We therefore investigated polymorphisms in the IL-10
      (-1082 G/A and -592 C/A) and IFNgamma (intron 1 CA repeat) genes as predisposing
      factors in the development 147 cases of HL. A difference of borderline
      statistical significance was demonstrated for the IFNgamma gene polymorphism but
      significance was lost when analysis was restricted to the common genotypes. No
      significant differences in the distributions of genotypes were found for the IL
      10 gene polymorphisms. IL-10 and IFNgamma levels were also measured on 26
      patients with HL. No statistically significant differences were detected when the
      results were analysed by genotype. We found little evidence IL-10 and IFNgamma
      genotypes predispose to the development of HL or influence the inflammatory host
      response.

PMID- 14959852
TI  - Prognostic significance of microvessel density and vascular endothelial growth
      factor (VEGF) expression in non-Hodgkin's lymphoma.
AB  - Angiogenesis has a major role in the pathogenesis of malignancies. Studies
      involving the role of angiogenesis have been most commonly performed in solid
      tumors. However, studies related to hemapoietic neoplasia and angiogenesis are
      relatively limited. We investigated the role of angiogenesis in non-Hodgkin's
      lymphomas (NHLs) and its relation with clinical and histopathologic prognostic
      indicators. In this respect, angiogenesis markers were evaluated in 71 patients
      with NHL and these were compared with other prognostic indicators including age,
      gender, histological grade, stage, extranodal involvement and survival.
      Microvessel density (MVD) using Factor VIII monoclonal antibody and vascular
      endothelial growth factor (VEGF) using monoclonal antibody for VEGF expression
      were studied in paraffin-embedded tissue samples. We did not find a significant
      relationship between MVD and patient characteristics including age, gender,
      stage, histological grade, nodal status, international prognostic index (IPI),
      and response to treatment. MVD was found to be greater in cases with B symptoms
      compared to those without B symptoms (14.6 +/- 5.7 and 11.4 +/- 5.3,
      respectively, p = 0.002). No significant relationship was found between VEGF and
      age, gender, stage, histological grade, IPI, and overall survival. The complete
      and partial response rate to therapy was significantly higher in VEGF-negative
      patients than in the VEGF-positive patients (p = 0.003). In conclusion, there
      appears to be a role for angiogenesis and angiogenic factors in NHLs. The
      combination of anti-angiogenic drugs with conventional anti-neoplastic treatment
      will probably be used in the future. Larger series of patients are needed to
      determine the prognostic value of angiogenesis in NHL.

PMID- 14959853
TI  - Infliximab for the treatment of severe steroid refractory acute graft-versus-host
      disease in three patients after allogeneic hematopoietic transplantation.
AB  - Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic
      peripheral blood stem cell transplantation (PBSCT). Patients with severe aGVHD
      not responding to treatment with steroids have a poor prognosis. We treated three
      patients with severe aGVHD refractory to steroids with infliximab. Patients (MDS
      1, NHL 1, ALL 1) developed grade II-IV GVHD at a median of 13 days (range 9-17)
      after non-myeloablative PBSCT (HLA mismatched). All patients had received
      treatment with high-dose steroids for a median of 7 days (range 7-10) in addition
      to mycophenolate mofetil (MMF) (one). Infliximab was given in 3 weekly doses of 5
      mg/kg. In one of three patients a partial resolution of diarrhea and minor
      improvement of skin were observed. One patient died with refractory GVHD.
      Infliximab is apparently an effective drug for the treatment of aGVHD, but can be
      more effective at doses of 5 mg/kg or higher and/or by administering it
      repeatedly every week.

PMID- 14959854
TI  - Pre-natal, clonal origin of acute lymphoblastic leukaemia in triplets.
AB  - A unique case of ALL in three monozygotic triplets diagnosed at the age of 24, 27
      and 37 months is described. Archived bone marrow smears were available for
      molecular analysis of immunoglobulin heavy chain (IGH) and IGK genes and T-cell
      receptor (TCR)-delta and gamma gene rearrangements. A shared IGH rearrangement
      was found in triplets "A" and "B", and an identical rearrangement of TCR-delta in
      triplets "B" and "C". These data suggest a common, monoclonal initiation of ALL
      in one of these three triplets, followed by dissemination of clonal progeny to
      the other twins via vascular anastomoses within the single, monochorionic
      placenta that they shared in utero. Differences in IGH rearrangements in
      diagnostic samples also indicates divergent subclonal evolution of the original
      "pre-leukaemic" clone.

PMID- 14959855
TI  - Autoimmune thrombocytopenia in chronic myeloid leukemia treated with interferon
      alpha: differential diagnosis and possible pathogenesis.
AB  - Interferon-alpha (INF-alpha) is an effective anti-neoplastic and anti-viral drug.
      Treatment with INF-alpha is frequently complicated by adverse effects, which may
      rarely be immune mediated. We report 2 patients with Ph+ chronic myeloid leukemia
      (CML) who developed autoimmune thrombocytopenia while receiving months of
      treatment with INF-alpha. This complication responded well to discontinuation of
      interferon and administration of steroids treatment. Here, we also summarize the
      literature on INF-alpha induced autoimmune thrombocytopenia, and discuss
      differential diagnosis and possible mechanisms involved in the development of
      thrombocytopenia during therapy with INF-alpha.

PMID- 14959857
TI  - CMRF44+ dendritic cells from peripheral blood stem cell harvests of patients with
      myeloma as potential cellular vectors for idiotype vaccination.
AB  - The optimal conditions required to harvest dendritic cells (DC) for immunotherapy
      were investigated in a series of preliminary investigations using peripheral
      blood stem cell (PBSC) harvests and blood from patients with myeloma. There was
      no difference in the number of DC (CMRF44+, CD19-, CD14-) in PBSC mobilized with
      G-CSF (mean 0.28%, n = 7) compared with GM-CSF (mean 0.24%, n = 6) and apheresis
      itself did not concentrate DC. In longitudinal studies (n = 10), the peak DC
      count (day 12 post PBSC harvest) did not correlate with the peak CD34+ cell count
      or white cell count. A simple affinity purification of DC resulted in a mean 63
      fold purification. Affinity enriched suspensions from normal blood contained more
      DC (mean = 18.8%; n = 5) than those from patients with myeloma (mean = 9.9%; n =
      13). The percentage of DC with a lymphoid phenotype (CD11c-, CDw123hi+) was
      significantly higher in G-CSF mobilized PBSC harvests (22.7%; n = 6) than in
      peripheral blood samples from patients with myeloma (7.0%; n = 13; p = 0.01). DC
      endocytosis was normal and did not change throughout the course of the disease.
      Neither DC numbers nor subsets changed significantly between days 1 and 3 of
      culture. Current mobilization procedures, optimized for PBSC, need to be altered
      when harvesting DC.

PMID- 14959856
TI  - Physiological oxidants induce apoptosis and cell cycle arrest in a multidrug
      resistant natural killer cell line, NK-YS.
AB  - Natural-killer (NK) cell-derived malignant tumors, such as angiocentric lymphoma,
      is often resistant to various chemotherapeutic agents and follows an aggressive
      clinical course. We report the effects of physiological oxidants (hydrogen
      peroxide, H2O2; sodium hypochlorite, NaOCl and monochloramine, NH2Cl) on the cell
      growth and cell death in a multidrug-resistant NK tumor cell line, NK-YS. Among
      the oxidants tested, NH2Cl was most cytotoxic, in which more than 90% of the
      cells died at 150 nmol/1 x 10(6) cells. H2O2 was less cytotoxic, whereas NaOCl
      showed no significant cell death at this dose. The cell death induced by NH2Cl
      was accompanied by DNA cleavage and caspase activation, which suggested
      apoptosis. In addition, lower dose of NH2Cl (70 nmol/1 x 10(6) cells) retarded
      cell growth and inhibited the cell cycle transition from G1 to S. This cell cycle
      arrest accompanied a decrease in the phosphorylation of retinoblastoma tumor
      suppressor protein at serine 795. These observations suggest that NH2Cl may
      induce apoptotic cell death and growth arrest in multidrug-resistant NK cell
      tumors.

PMID- 14959858
TI  - Farnesyl transferase inhibitors enhance death receptor signals and induce
      apoptosis in multiple myeloma cells.
AB  - Multiple myeloma is an incurable plasma cell malignancy in which Ras may be
      constitutively active either via interleukin-6 (IL-6) receptor signaling or by
      mutation. Inactivation of Ras may be achieved with farnesyl transferase (FTase)
      inhibitors a class of drugs which have shown promise in clinical trials
      particularly in patients with acute leukemia. This report investigates the
      efficacy of two distinct classes of FTase inhibitors in diverse myeloma cell
      lines and primary isolates. While Ras signaling has traditionally been linked to
      myeloma cell growth, we found that these compounds also potently triggered cell
      death. Death induced by perillic acid (PA) was caspase dependent without evidence
      of death receptor activation. Apoptosis was associated with mitochondrial
      membrane depolarization and activation of caspase-9 and 3 but proceeded despite
      over-expression of Bcl-XL a known correlate of relapsed and chemorefractory
      myeloma. In addition, Fas ligand and TRAIL mediated apoptosis was potentiated in
      death receptor resistant (U266) and sensitive (RPMI 8226/S) cell lines. Of
      clinical relevance, the FTase inhibitor R115777 induced cell death in myeloma
      lines at doses observed in clinical trials. Furthermore, both R115777 and PA
      induced cell death in primary isolates with relative specificity. Taken together
      these preclinical data provide evidence that FTase inhibitors may be an effective
      therapeutic modality for the treatment of multiple myeloma.

PMID- 14959859
TI  - Induction of complete remission using single agent clofarabine in a patient with
      primary refractory acute myeloblaste leukemia.
AB  - Refractory AML patients have a very poor prognosis. Therefore, rationally
      designed new therapies, including clofarabine, are being investigated as
      potential treatments for this patient population. This is a case report of a
      patient with primary refractory AML who was treated with clofarabine and achieved
      a complete response.

PMID- 14959860
TI  - Hematological remission and long term hematological control of acute myeloblastic
      leukemia induced and maintained by granulocyte-colony stimulating factor (G-CSF)
      therapy.
AB  - We describe a case of a patient with CD34+, TdT+, CD13-, CD33-, MPO-
      undifferentiated acute leukemia who refused chemotherapy and who achieved
      complete hematological remission 14 months after the diagnosis, during a short
      course of granulocyte-colony stimulating factor (G-CSF) for neutropenia and life
      threatening infection. Relapse occurred approximately one year later and G-CSF
      was reintroduced, being maintained for 4 months, at a dose and frequency adapted
      to maintain normal blood counts, a complete hematological remission being
      achieved again. Five months after withdrawing the G-CSF therapy a second relapse
      was observed; G-CSF was tried again with success, resulting in a very good
      hematological response that was sustained by G-CSF maintenance therapy. One year
      latter there was the need of increasing the doses of G-CSF in order to obtain the
      same hematological effect, at same time blast cells acquired a more mature CD34+,
      TdT-, CD13+, CD33-, MPO+ myeloid phenotype. Finally, the patient developed
      progressive neutropenia, anemia, thrombocytopenia and acute leukemia in spite of
      G-CSF therapy, dying 64 months after initial diagnosis (50 months after starting
      G-CSF therapy) with overt G-CSF resistant acute myeloblastic leukemia (AML),
      after failure of conventional induction chemotherapy.

PMID- 14959861
TI  - Acute myelogenous leukemia with splenic infarcts presenting as fulminant multi
      organ failure.
AB  - A 60-year-old male was admitted with leukopenia, thrombocytopenia, splenic
      infarcts and a normal peripheral smear. Within few hours he rapidly deteriorated
      with fatal multi-organ failure. Autopsy revealed massive infiltration of leukemic
      cells in several organs. Acute myelogenous leukemia should be considered in a
      patient presenting with unexplained multiorgan failure.

PMID- 14959862
TI  - Phagocytosis of terminally differentiated acute promyelocytic leukemia cells by
      marrow histiocytes during treatment with all-trans retinoic acid.
AB  - It has been established that acute promyelocytic leukemia (APL) cells are induced
      to terminally differentiate by all-trans retinoic acid (ATRA), however, the
      clearance of differentiated APL cells in vivo has not been well understood. Here,
      we documented the elimination of terminally differentiated APL cells by
      histiocytes in bone marrow during differentiation induction therapy. In two ATRA
      treated APL patients, bone marrow showed the striking phagocytosis of
      differentiated APL cells by histiocytes just before the achievement of complete
      remission. Histiocytes phagocytosed APL cells at the terminal stage of
      differentiation prior to the late apoptotic event of cell lysis. Engulfed APL
      cells then undergo morphological features of late apoptosis and finally
      fragmentation in the cytoplasm of histiocytes. This swift and efficient
      elimination of APL cells undergoing apoptosis by the histiocytes in bone marrow
      may be possible pathway, at least partially, for the clearance of differentiated
      APL cells.

PMID- 14959863
TI  - Variant Richter's syndrome: a rare case of classical Hodgkin's lymphoma
      developing in a patient with chronic lymphocytic leukemia treated with
      fludarabine.
AB  - We report a case of a 52-year-old male who developed classical Hodgkin's lymphoma
      (HL) four years after diagnosis of stage Rai II (Binet B) chronic lymphocytic
      leukemia (CLL). The patient was treated with fludarabine and cyclophosphamide
      with partial response. Subsequently, he presented with a 6-month history of
      weight loss and fatigue, and 6 weeks of fever, a progressively enlarged liver and
      elevated serum LDH level. An inguinal lymph node biopsy revealed both classical
      Hodgkin's lymphoma, nodular sclerosing type grade 2 and CLL. A bone marrow biopsy
      showed no Reed-Steinberg cells and an infiltrate composed of only scattered small
      lymphocytes consistent with CLL. Immuno-histochemical studies of the lymph node
      were consistent with both CLL and HL phenotypes. A cytogenic examination of the
      bone marrow revealed an abnormal karyotype (Y-) in 15% of the cell population.
      Treatment with MOPP/ABVD was started and fever subsided within 3 days. Our case
      is one of the very few descriptions of a rare Richter's variant of CLL with
      progression to HL in a CLL patient treated with fludarabine. Since fludarabine
      has become standard therapy in CLL such Richter's variant could be the result of
      therapy, an induced prolonged and severe immunosuppression. Clinicians should be
      aware of such association, which could become more frequent among CLL patients
      treated with purine analogs.

PMID- 14959864
TI  - Non-Hodgkin's lymphoma involving the uterine cervix after treatment for Hodgkin
      disease.
AB  - The occurrence of second malignancies is an important late event following the
      treatment of Hodgkin's disease (HD). Occurrence of a non-Hodgkin's lymphoma (NHL)
      involving the uterine cervix after treatment for HD has not been previously
      reported. We describe a rare case of a 34-year old woman, with NHL involving the
      uterine cervix 7.5 years after treatment for HD. The follow-up of patients
      treated for HD should also include regular gynecological evaluation. In cases of
      abnormal findings, accurate diagnosis can only be made histologically.

PMID- 14959865
TI  - Childhood T-acute lymphoblastic leukemia relapsed as minimally differentiated
      acute myeloid leukemia (AML-M0).

PMID- 14959866
TI  - High-dose therapy supported by autologous stem cell transplantation in patients
      with enteropathy-associated T-cell lymphoma.

PMID- 14959867
TI  - Successful rituximab therapy for hemolytic anemia associated with relapsed
      splenic marginal zone lymphoma with leukemic phase.

PMID- 14959868
TI  - It ain't necessarily so: Mars and the limits of received wisdom.

PMID- 14959869
TI  - Light-curing times.

PMID- 14959870
TI  - Informed consent.

PMID- 14959871
TI  - Manual dexterity.

PMID- 14959872
TI  - Profession or business?

PMID- 14959873
TI  - Guidelines for infection control in dental health care settings--2003.
AB  - BACKGROUND: The Centers for Disease Control and Prevention, or CDC, is the lead
      federal agency for disease prevention in the United States. It has been 10 years
      since CDC infection control guidelines for dental health care settings were last
      published. During those 10 years, new technologies and issues have emerged, and
      other CDC infection control guidelines for health care settings have been
      updated. RESULTS: In light of these developments, CDC collaborated with experts
      in infection control to revise its infection control recommendations for dental
      health care settings. Existing guidelines and published research pertinent to
      dental infection control principles and practices were reviewed. This article
      provides background information, describes the process used to create these
      guidelines, and lists the new recommendations. CLINICAL IMPLICATIONS: CDC
      believes that dental offices that follow these new recommendations will
      strengthen an already admirable record of safe dental practice. Patients and
      providers alike can be assured that oral health care can be delivered and
      received in a safe manner.

PMID- 14959874
TI  - Treatment modalities and medication recommended by health care professionals for
      treating recurrent herpes labialis.
AB  - BACKGROUND: The authors conducted a survey to determine how health care
      professionals respond to patients' inquiries about cold sores, also known as
      recurrent herpes labialis, and their choices of treatment modalities and
      medications. METHODS: The authors mailed a one-page, pretested survey to a random
      sample of dentists, pharmacists and family physicians in Alberta, Canada. After
      receiving ethics approval from the University of Alberta, Edmonton, the authors
      mailed 998 surveys. The response rate was 51 percent. RESULTS: Topical antiviral
      medication was the most common treatment recommended (63 percent). Over-the
      counter medication was the first choice for pharmacists (83 percent) as compared
      with dentists (15 percent) and physicians (16 percent). Emotional stress (60
      percent) was reported by patients to be the most common trigger, and pain or
      discomfort (81 percent) was their primary concern. Acyclovir ointment was the
      most common antiviral drug recommended or prescribed by health care professionals
      (60 percent), and cost was the major reason they gave for not recommending or
      prescribing antiviral drugs (73 percent). CONCLUSIONS: The authors found
      variation in treatment modalities and recommendations by each health profession,
      despite the fact that patients reported similar triggers and concerns. This may
      be due to individual patient need and the health care professional's lack of
      knowledge. PRACTICE IMPLICATIONS: Survey results may serve as a reference for
      health care professionals to use to determine how their choices of medications
      and treatment modalities compare with those of other practitioners. Professionals
      should know the benefits and limitations of all therapies, discuss them with the
      patients and select a treatment.

PMID- 14959875
TI  - The relationship between healthful eating practices and dental caries in children
      aged 2-5 years in the United States, 1988-1994.
AB  - BACKGROUND: As a result of the introduction of multiple fluoride vehicles and
      other preventive agents, caries prevalence rates in young children have been
      declining over the past two decades in the United States. However, changing
      dietary patterns in young children may offset some of the oral health benefits of
      fluoridation. The objective of this study was to examine the relationship between
      caries in primary teeth and healthful eating practices in young children.
      METHODS: The authors used data from the third National Health and Nutrition
      Examination Survey to investigate the relationship between healthful eating
      practices (such as breast-feeding, eating breakfast and consuming five servings
      of fruits and vegetables a day) and dental caries (untreated tooth decay and
      overall caries experience) in the primary dentition among children aged 2 through
      5 years. RESULTS: The odds of experiencing caries in primary teeth were
      significantly greater in nonpoor children who did not eat breakfast daily or ate
      fewer than five servings of fruit and vegetables per day (odds ratio, or OR =
      3.77; 95 percent confidence interval, or CI, 1.80 to 7.89 and OR = 3.21; 95
      percent CI, 1.74 to 5.95, respectively). No association was found between breast
      feeding and caries in primary teeth. CONCLUSION: Young children with poor eating
      habits are more likely to experience caries. Overall, the findings support the
      notion that dental health education should encourage parents, primary caregivers
      and policy-makers to promote healthful eating practices, such as eating breakfast
      daily, for young children. PRACTICE IMPLICATIONS: Dental professionals are well
      positioned to inform parents and caregivers regarding age-appropriate healthful
      eating practices for young children entrusted in their care.

PMID- 14959876
TI  - Preparing dental students to recognize and respond to domestic violence: the
      impact of a brief tutorial.
AB  - BACKGROUND: The purpose of this study was to evaluate the impact of a brief,
      interactive multimedia tutorial designed to prepare dentists to recognize and
      respond to domestic violence. METHODS: The authors randomly assigned dentists and
      dental students to one of three groups: a control group or one of two
      experimental groups in a modified Solomon four-group design. RESULTS: One hundred
      sixty-one dental students and 13 dentists completed the multimedia tutorial. At
      the posttest, subjects in both experimental groups demonstrated significantly
      better scores than did subjects in the control group on most items. The two
      experimental groups (pretest and posttest, posttest only) did not differ
      significantly from each other. CONCLUSION: An engaging, interactive tutorial
      presenting a simplified model for ways in which dental professionals can
      recognize and respond to domestic violence significantly improved dental
      students' knowledge of, and attitudes toward, the topic. CLINICAL IMPLICATIONS:
      Clinicians may improve the care they provide to patients by accessing this brief
      tutorial and following the lessons contained in it.

PMID- 14959877
TI  - Gifts to give yourself for the new year.
AB  - Dentistry can offer its dedicated practitioners a wonderful, productive, service
      oriented life, with an acceptable income. However, numerous circumstances can
      turn what could be a happy life into a nightmare of frustration and negative
      feelings. This article has identified several of the challenges facing
      practitioners. If these challenges are faced and solutions implemented, the
      possibility of the practitioner's maintaining a happy life is greatly improved.

PMID- 14959878
TI  - Evidence-based dentistry in clinical practice.
AB  - BACKGROUND: Evidence-based dentistry, or EBD, is not a new concept for the dental
      profession in the United States. The American Dental Association has long relied
      on credible scientific evidence in setting policy and communicating with dentists
      and the general public. EBD provides an approach to oral health care that follows
      a process of systematically collecting and analyzing scientific evidence to
      answer a specific clinical question. OVERVIEW: The authors discuss applications
      of systematic review findings to everyday clinical practice and explore the
      implications of EBD for dental education, clinical research and the provision of
      care to patients. CONCLUSIONS AND PRACTICE IMPLICATIONS: In developing
      appropriate treatment plans, dentists should combine the patient's treatment
      needs and preferences with the best available scientific evidence, in conjunction
      with the dentist's clinical expertise. To keep pace with other health professions
      in building a strong evidence-based foundation, dentistry will require
      significant investments in clinical research and education to evaluate the best
      currently available evidence in dentistry and to identify new information needed
      to help dentists provide optimal care to patients.

PMID- 14959879
TI  - Safeguarding the health of dental professionals.
AB  - BACKGROUND: A healthy dentist is one of the most important ingredients in a
      successful dental practice, an ingredient not to be taken for granted.
      Professionals, dentists included, can and do experience illnesses and problems
      that can disrupt or impair a practice. CONCLUSIONS: In addition to the
      vulnerabilities of the human condition--addictive disorders, psychiatric
      illnesses, infectious disease, family and relationship problems, or the many
      varieties of human misery--dentists have undergone a powerful process of
      socialization into their professional role that makes it difficult to seek help
      for themselves. Stigma about addictive and psychiatric illnesses continues to be
      a problem despite significant advances in scientific understanding of these
      disorders. Many people, especially those in positions of community visibility as
      dentists are, still struggle with shame when they associate problems with
      personal failure. Dental societies are in an ideal position to provide resources
      and support, should they choose to take this opportunity, and the ADA has the
      information and expertise to help them do this. PRACTICE IMPLICATIONS: Dentists
      can become more aware of their own vulnerabilities and enhance their personal and
      professional effectiveness, as well as evaluate ways they may support their staff
      and colleagues.

PMID- 14959880
TI  - Action planning and accountability.
AB  - The truth is that no plan survives its collision with reality. The best plan does
      not guarantee that the dentist will not go over budget on building a new practice
      or run into unexpected obstacles in integrating a new software into the practice.
      The best plan does not guarantee that goals will be met precisely on schedule.
      What a plan does guarantee is that the dentist has provided the practice with the
      best opportunity to achieve goals on time and within budget by executive
      analyzing and charting a clear path toward success. Smart businesses understand
      the process of vision clarification of vision clarification and goal setting, but
      do not stop there. Smart businesses define clear AP&A systems that effectively
      chart a path toward goal attainment, then proceed to implement that plan and
      monitor progress toward goals. In instances in which information becomes
      available indicating the plan needs to be revised, corrective action is taken and
      appropriate changes are made.

PMID- 14959881
TI  - Dental endosseous implants: an update.
AB  - BACKGROUND: The ADA Council on Scientific Affairs has developed an updated report
      on endosseous implants to aid dental professionals in considering and
      incorporating practical applications of implantation therapy in general practice.
      OVERVIEW: This report addresses the demonstrated high success rates of multiple
      implant designs in various clinical situations, the factors contributing to
      elevated risk of implant failure and implantation therapy as a comprehensive
      process of patient care. The Council also provides a list of products available
      to the profession that have received the ADA Seal of Acceptance. CONCLUSIONS AND
      PRACTICE IMPLICATIONS: The Council recommends that practitioners use implantation
      therapies and systems judiciously in accordance with the current best evidence.
      The Council also urges evaluators to use common and consistent criteria for
      reporting the outcomes assessment in clinical studies of various implant
      treatments.

PMID- 14959882
TI  - Vital bleaching with a thin peroxide gel: the safety and efficacy of a
      professional-strength hydrogen peroxide whitening strip.
AB  - BACKGROUND: Use of higher peroxide concentrations for professional at-home vital
      bleaching often balances two factors in patient compliance: whitening and
      tolerability. Development of a polyethylene strip coated with a very thin (0.10
      millimeter) layer of 14 percent hydrogen peroxide gel (Crest Whitestrips Supreme,
      Procter & Gamble, Cincinnati)--which represents an increase in concentration and
      a decrease in amount of gel--was believed to allow for greater at-home whitening
      with little additional oral soft-tissue exposure to peroxide. METHODS: The
      authors conducted a randomized, double-blind, two-week clinical trial with 38
      adults to evaluate the safety and efficacy of twice-daily use of the thin,
      concentrated bleaching gel strip versus the effects of a control product (Crest
      Whitestrips, Procter & Gamble). The two products differed only in concentration
      (14 percent versus 6 percent) and gel layer thickness (0.10 mm versus 0.20 mm).
      The authors measured efficacy from digital images using the Commission
      Internationale de l'Eclairage L*a*b* color scale. They assessed safety via
      subject interviews and clinical examination and compared treatments using
      analysis of covariance. RESULTS: Relative to baseline color, both strip groups
      exhibited significant (P < .001) improvement in yellowness, brightness and
      composite color change. Between-group comparisons after two weeks demonstrated
      significant (P < .003) color improvement for the experimental strip relative to
      the control. Both products were well-tolerated generally. Despite the
      concentration differences, clinical examination of each group showed a similar
      low level (11 percent) of "minor oral irritation." CONCLUSION: Use of the thin 14
      percent hydrogen peroxide gel strip resulted in greater whitening, including 42
      to 49 percent greater improvement in tooth color and faster whitening onset than
      that seen with a 6 percent hydrogen peroxide whitening strip, without clinical
      evidence of increased oral-tissue irritation. CLINICAL IMPLICATIONS: Use of
      whitening strips with a thin, concentrated layer of hydrogen peroxide gel may
      represent a useful approach for professionally directed at-home vital bleaching.

PMID- 14959883
TI  - Sterilizer.

PMID- 14959884
TI  - Supreme Court to decide whether ERISA pre-empts negligence claims against HMOs.

PMID- 14959885
TI  - For the dental patient. Pregnant? Tips for keeping your smile healthy.

PMID- 14959886
TI  - An unsaturated peptidomimetic assembly derived from a carbohydrate.
AB  - A strategy has been established for the synthesis of peptidomimetics derived from
      unsaturated carbohydrates, and exemplified by the use of methyl 2,6-anhydro-7
      azido-3,7-deoxy-4,5-O-isopropylidene-D-lyxo-hept-2-enonate 9 as a dipeptide
      'monomer' which can be elaborated from either end. Selective reduction of 9 gives
      a protected pseudodipeptide ester suitable for use as an amino component, and
      saponification gives an azido acid suitable for use as a carboxyl component. The
      'dimer' product of coupling these two components with TBTU can be similarly
      elaborated at either end to give a 'trimer' and a further cycle of selective
      reduction and coupling gave a 'tetramer', 17, a pseudo-octapeptide.

PMID- 14959887
TI  - Oligopeptide-mediated acceleration of amyloid fibril formation of amyloid
      beta(Abeta) and alpha-synuclein fragment peptide (NAC).
AB  - The effects of oligopeptides on the secondary structures of Abeta and NAC, a
      fragment of alpha-synuclein protein, were studied by circular dichroism (CD)
      spectra. The effects of oligopeptides on the amyloid fibril formation were also
      studied by fluorescence spectra due to thioflavine-T. The oligopeptides were
      composed of a fragment of Abeta or NAC and were interposed by acidic or basic
      amino acid residues. The peptide, Ac-ELVFFAKK-NH2, which involved a fragment Leu
      Val-Phe-Phe-Ala at Abeta(17-21), had no effect on the secondary structures of
      Abeta(1-28) in 60% or 90% trifluoroethanol (TFE) solutions at both pH 3.2 and pH
      7.2. However, it showed pronounced effects on the secondary structure of Abeta(1
      28) at pH 5.4. The Ac-ELVFFAKK-NH2 reduced the alpha-helical content, while it
      increased the beta-sheet content of Abeta(1-28). In phosphate buffer solutions at
      pH 7.0, Ac-ELVFFAKK-NH2 had little effect on the secondary structures of Abeta(1
      28). However, it accelerated amyloid fibril formation when monitored by
      fluorescence spectra due to thioflavine-T. On the other hand, LPFFD, a peptide
      known as a beta-sheet breaker, caused neither an appreciable extent of change in
      the secondary structure nor amyloid fibril formation in the same buffer solution.
      The peptide, Ac-ETVK-NH2, which involved a fragment Thr-Val at NAC(21-22), had no
      effect on the secondary structure of NAC in 90% TFE and in isotonic phosphate
      buffer. However, Ac-ETVK-NH2 in water with small amounts of NaN3 and
      hexafluoroisopropanol greatly increased the beta-sheet content of NAC after
      standing the solution for more than 1 week. Interestingly, in this solution. Ac
      ETVK-NH2, accelerated the fibril formation of NAC. It was concluded that an
      oligopeptide that involves a fragment of amyloidogenic proteins could be a
      trigger for the formation of amyloid plaques of the proteins even when it had
      little effect on the secondary structures of the proteins as monitored by CD
      spectra for a short incubation time.

PMID- 14959888
TI  - Expediting the Fmoc solid phase synthesis of long peptides through the
      application of dimethyloxazolidine dipeptides.
AB  - This paper describes the step-wise Fmoc solid phase synthesis of a 95-residue
      peptide related to FAS death domain. Attempts to prepare this peptide employing
      conventional amino acid building blocks failed. However, by the judicious use of
      dimethyloxazolidine dipeptides of serine and threonine, the peptide could be
      readily prepared in remarkable purity by applying single 1 h coupling reactions.

PMID- 14959889
TI  - Synthesis and structure-activity relationship of new analogues of antistasin.
AB  - Intensive investigation connected with the development of new anticoagulant
      agents for the treatment of cardiovascular diseases was carried out. Direct and
      specific inhibition of thrombin and Factor Xa-like serine proteases in the
      coagulation cascade has been the focus of many efforts to design novel
      anticoagulants over the past decade. This work reports the synthesis and
      biological activity of new anticoagulant peptide analogues of natural isoforms 2
      and 3 of antistasin. In addition they include different tripeptide sequences in
      their molecules, which are highly active inhibitors of different serine proteases
      such as plasmin, trypsin, thrombin and Factor Xa.

PMID- 14959890
TI  - The effects of shortening lactoferrin derived peptides against tumour cells,
      bacteria and normal human cells.
AB  - A number of shortened derivatives of the lactoferrin model peptide L12,
      PAWRKAFRWAKRMLKKAA, were designed in order to elucidate the structural basis for
      antitumour activity of lactoferrin derivatives. Three tumour cell lines were
      included in the study and toxicity determined by measuring lysis of human red
      blood cells and fibroblasts. The results demonstrated a strong correlation
      between antitumour activity and net positive charge, in which a net charge close
      to +7 was essential for a high antitumour activity. In order to increase the
      antitumour activity of the shortest peptide with a net charge less than +7, the
      hydrophobicity had to be increased by adding a bulky Trp residue. None of the
      peptides were haemolytic, but toxicity against fibroblasts was observed. However,
      modifications of the peptides had a higher effect on reducing fibroblast toxicity
      than antitumour activity and thereby resulted in peptides displaying an almost 7
      fold selectivity for tumour cells compared with fibroblasts. The antimicrobial
      activity against the Gram-negative bacteria Escherichia coil and the Gram
      positive bacteria Staphylococcus aureus was also included in order to compare the
      structural requirements for antitumour activity with those required for a high
      antimicrobial activity. The results showed that most of the peptides were highly
      active against both bacterial strains. Less modification by shortening the
      peptide sequences was tolerated for maintaining a high antitumour activity and
      selectivity compared with antimicrobial activity. The order of the amino acid
      residues and thereby the conformation of the peptides was highly essential for
      antitumour activity, whereas the antimicrobial activity was hardly influenced by
      changes in this parameter. Thus, in addition to a certain net positive charge and
      hydrophobicity, the ability to adopt an amphipathic conformation was a more
      critical structural parameter for antitumour activity than for antimicrobial
      activity, and implied that a higher flexibility or number of active conformations
      was tolerated for the peptides to exert a high antimicrobial activity.

PMID- 14959891
TI  - Novel carbohydrate-induced modification of peptides: crystal structure and NMR
      analysis of ester-bridged bicyclic galactose-enkephalin adduct containing
      imidazolidinone moiety.
AB  - Comparative studies based on x-ray crystallography and NMR spectroscopy were used
      for structural characterization of the novel minor, imidazolidinone moiety
      containing, product 2b of the Maillard reaction obtained in vitro by using the
      galactose-modified endogenous opioid pentapeptide leucine-enkephalin (Tyr-Gly-Gly
      Phe-Leu) 1. The x-ray analysis uniquely defined the molecular structure as cyclo
      (N-(12-[-4)-D-galacto-pentitol-1-yl]-4-(4-hydroxybenzyl)-5-oxoimidazolidin-1-yl
      (1 --> O]acetyl]glycyl-L-phenylalanyl-L-leucyl-] (3), having an 18-membered ring
      with an ester bond between the secondary (C4') hydroxyl group of a D-galacto
      pentitolyl residue and the C-terminal carboxy group of leucine-enkephalin. The
      absolute configuration of the new chiral centre at the imidazolidinone moiety was
      established as C2(S), indicating a cis arrangement of C2 and C4 substituents at
      the 5-membered heterocyclic ring. The NMR analysis of compound 2b carried out in
      CH3CN-d3 and DMSO-d6, indicated the existence of two isomers in solution,
      differing only in the position of the ester group in the molecule. NMR data for
      the minor isomer (13%-16%) are in agreement with structure 3. The migratory
      tendency of the peptidyl group from the primary (2b) to the secondary hydroxyl
      group (3) of a D-galacto-pentitolyl residue in methanol/water solution was
      confirmed by RP HPLC analysis.

PMID- 14959892
TI  - Heteroclitic recognition of combinatorial TX1TX2T peptide mixtures by mucin-2
      protein specific monoclonal antibody.
AB  - The mucin-2 (MUC2) glycoprotein secreted by the epithelial cells of human colon
      may be abnormally under-glycosylated in the case of cancer. Monoclonal antibody
      (mAb) 994 raised against the immunogenic part of the protein core, recognizes
      malignant human colon tissues as well as pentapeptides with TX1TX2T motif present
      in MUC2. Using a combinatorial approach and ELISA experiments it was found that
      mAb 994 is able to recognize peptides of the sub-library TQTX2T very strongly,
      and to some extent also peptides from TETX2T, TLTX2T and TVTX2T sub-libraries.
      Binding studies with peptides corresponding to the TQTX2T and TETX2T sub
      libraries showed that mAb 994 recognized only six peptides (IC50 = 9-208 micromol
      dm(-3)) from the 19 compounds of the TQTX2T sub-library and only three peptides
      (IC50 = 3500-16700 micromol dm(-3)) from the 'second-best' TETX2T sub-library.
      The most pronounced mAb binding occurred when Gln was in position X1 and it was
      much weaker in the case of Glu, Val or Leu. As for X2 amino acids, the presence
      of Pro, Ala can provide a strong, while Tyr, Trp, Phe and Ser a weaker, peptide
      antibody interaction. Data from this study suggest that pentapeptide TQTPT, whose
      sequence is present in the native protein, is bound most strongly. However,
      almost identical binding properties were observed with peptide TQTAT, whose
      sequence is not present in the protein. Apart from this, some other
      'heteroclitic' peptides were found with a different rank in the binding
      hierarchy. Based on these peptides artificial compounds can be prepared as
      potential candidates for vaccine development. Results of this study also provide
      a rationale for understanding the molecular background of the heteroclitic nature
      of the MUC2 protein core specific mAb 994.

PMID- 14959894
TI  - Managerial competencies necessary in today's dynamic health care environment.
AB  - The traditional functions of management--planning, organizing, leading, and
      controlling--continue to be the key activities used to enable the organization to
      accomplish its goals and objectives. Though significant changes have occurred in
      all organizational structures, processes, and managerial styles, these
      traditional functions remain a constant. What has undergone significant change,
      as this article examines, are the skills and competencies within each function,
      which managers must develop and employ if they are to be successful practitioners
      in today's dynamic health care organizations.

PMID- 14959895
TI  - The organizational huddle process--optimum results through collaboration.
AB  - The St. Joseph's Regional Medical Center in Paterson, New Jersey, initiated a
      methodology called The Organizational Huddle Process in the fall of 1999. This
      communication vehicle enhances operational performance through a fast, focused,
      and highly collaborative process. The results of this initiative have been most
      impressive. Hundreds of problems have been resolved before escalating to crisis
      levels, with an increase in stakeholder satisfaction. This process is appropriate
      for all levels within an organization, is effective for both interdisciplinary
      and departmental groups, and has minimal associated implementation costs. This
      article reviews the rationale and benefits of The Organizational Huddle Process,
      a recommended implementation strategy, and a nurse manager's review on the
      application of this methodology.

PMID- 14959896
TI  - Organizational culture: its impact on employee relations and discipline in health
      care organizations.
AB  - Organizations need to examine their cultures at the level of the "shop floor"--in
      health care, the point where health care workers deal with patients--to determine
      if the culture is consistent with management policies and will permit an
      effective program of reward and discipline. This article describes a case where
      organizational culture was a major imperative in the outcome of an arbitration
      case. Discussed is a shop-floor situation in manufacturing holding implications
      for health care, a setting in which management, by countenancing
      counterproductive aspects of the culture, made it impossible to apply discipline
      as needed. The conclusion is that health care organizations that neglect the
      detrimental elements of their culture may find themselves not only at risk of
      poor employee relations, but also unable to apply discipline effectively.

PMID- 14959897
TI  - When the health care manager is preoccupied with self-doubt.
AB  - Self-doubt may plague a manager and lead to lack of productiveness and
      unhappiness. This manuscript describes the negative effects of self-doubt and
      strategies that should be used if self-doubt occurs.

PMID- 14959898
TI  - Online degrees: a convenient alternative for health care professionals.
AB  - Online degrees are a convenient way for health care professionals to complete
      their degree, earn an advanced degree, or continue their education. Colleges all
      over the country are adding online courses and degrees to attract working adults
      who may not have the time to attend class the old-fashioned way.

PMID- 14959899
TI  - Managed care--present day challenges and a working model for future
      consideration.
AB  - With the emergence of managed care as a dominant form of coverage for the
      American workforce and the concomitant growth in the number of uninsured and
      underinsured citizens, attention is increasingly focused on the development of
      cost-effective and efficient reimbursement strategies for the future. This
      manuscript provides both a summation of the different forms of coverage now
      available and a look at a possible future scenario through the only universal
      health insurance program now in place in the United States--Hawaii's health care
      system.

PMID- 14959900
TI  - An analysis of computerization in primary care practices.
AB  - To remain profitable, primary care practices, the front-line health care
      providers, must provide excellent patient care and reduce expenses while
      providing payers with accurate data. Many primary care practices have turned to
      computer technology to achieve these goals. This study examined the degree of
      computerization of primary care providers in the Augusta, Georgia, metropolitan
      area as well as the level of awareness of the Health Insurance Portability and
      Accountability Act (HIPAA) by primary care providers and its potential effect on
      their future computerization plans. The study's findings are presented and
      discussed as well as a number of recommendations for practice managers.

PMID- 14959901
TI  - The manager and continuing education.
AB  - Continuing education in health care organizations consists of that which is
      required by law or regulation and that which is optional. The required is done
      because it must be done; the other, including most management development and
      some staff education, is often ignored. Nonrequired education is one of the first
      items to go during budget-cutting exercises. Yet continuing education at all
      levels, for managers as well as nonmanagers, is essential in keeping health care
      workers abreast of rapid change. Much continuing education, even that for rank
      and-file staff, is up to the department manager, and with few exceptions, the
      pursuit of continuing management development is left largely to the individual
      manager. The department manager is an educator of staff and is also largely
      responsible for self-development.

PMID- 14959902
TI  - A manager asks: motivational implications. Dealing with repetitive work.

PMID- 14959903
TI  - Effectiveness of 20% benzocaine as a topical anesthetic for intraoral injections.
AB  - The use of topical anesthetics has been advocated prior to the administration of
      various types of anesthetic injections. Reported results have varied between
      studies. The purpose of this study was to compare the effectiveness of 20%
      benzocaine in reducing the pain of needle insertion during maxillary posterior
      and anterior infiltration and inferior alveolar nerve block injections. In this
      retrospective study, 1080 patients received 2336 injections using a 27-gauge
      needle. Topical anesthetic was applied prior to 720 of the injections. Patients
      rated pain of needle insertion using a 0-4 pain scale. Logistic regression
      analysis showed no differences in pain ratings between topical and no topical
      groups for the inferior alveolar nerve block and posterior maxillary infiltration
      injections. The use of topical anesthetic did reduce the pain of needle insertion
      with the maxillary anterior injections (P = .0041).

PMID- 14959904
TI  - Comparison of effectiveness of 4% articaine associated with 1: 100,000 or 1:
      200,000 epinephrine in inferior alveolar nerve block.
AB  - This comparative study using 20 healthy volunteers evaluated the anesthetic
      efficacy of 4% articaine in association with 2 different concentrations of
      epinephrine, 1:200,000 (G1) and 1:100,000 (G2). The first premolars were tested
      with a pulp tester to verify the anesthesia induced by the inferior alveolar
      nerve block. The following parameters were measured: period of latency (PL;
      interval between the end of anesthetic injection and absence of response to the
      maximum output--80 reading--of the pulp tester); complete pulpal anesthesia (CPA;
      period in which the subject had no response to maximal output of the pulp tester
      80 reading); partial anesthesia (PA; interval between the first reading below 80
      and the return to basal levels); and the anesthesia of the soft tissues (AST;
      period of time from onset of anesthesia until the return to normal sensation of
      the lip). The Wilcoxon test (alpha = 0.05) was used to analyze the data. No
      significant difference was found regarding PL (P = .47), CPA (P = .88), PA (P =
      .46), and AST (P = .85). The results indicated that both solutions presented the
      same clinical effectiveness in blocking the inferior alveolar nerve.

PMID- 14959905
TI  - Comparative analysis of tissue reactions to anesthetic solutions: histological
      analysis in subcutaneous tissue of rats.
AB  - Postanesthetic pain is a relatively common complication after local anesthesia.
      This complication may be caused by the anesthetic technique or by the anesthetic
      solution used. Tissue reactions induced by the anesthetic solutions may be one of
      the factors resulting in pain after anesthesia. The objective of this study was
      to comparatively analyze tissue reactions induced by different anesthetic
      solutions in the subcutaneous tissue of rats. The following solutions were
      utilized: 2% lidocaine without vasoconstrictor; a 0.5% bupivacaine solution with
      1:200,000 adrenaline; a 4% articaine solution and 2% mepivacaine, both with
      1:100,000 adrenaline; and a 0.9% sodium chloride solution as a control.
      Sterilized absorbent paper cones packed inside polyethylene tubes were soaked in
      the solutions and implanted in the subcutaneous region. The sacrifice periods
      were 1, 2, 5, and 10 days after surgery. The specimens were prepared and stained
      with hematoxylin and eosin for histological analysis. The results showed that
      there is a difference in tissue irritability produced by the local anesthetic
      solutions. The results also showed that there is no relation between the
      concentration of the drug and the inflammatory intensity, that the mepivacaine
      and articaine solutions promoted less inflammatory reaction than the bupivacaine,
      and that the lidocaine solution produced the least intense inflammation.

PMID- 14959906
TI  - Evaluation of surgical procedures for trigeminal neuralgia.
AB  - Trigeminal neuralgia is a type of facial pain that is difficult to treat. The
      pain can be excruciating and debilitating. The wide range of treatments currently
      used for trigeminal neuralgia is ample evidence that there is no simple answer to
      how it should be managed. This review will evaluate the current surgical
      procedures used for the treatment of trigeminal neuralgia. A critical analysis of
      the evidence-based studies to date was done to evaluate and compare the efficacy
      of the different surgical procedures. Arguments for and against the use of
      surgery for trigeminal neuralgia are presented. In addition, the surgical
      procedures were compared with other treatments for trigeminal neuralgia.

PMID- 14959907
TI  - Undue extension of hospital stay associated with anticoagulation.

PMID- 14959908
TI  - Effect of intravenous heparin administration on duration of hospitalization.
AB  - OBJECTIVE: To determine how frequently hospital discharge is delayed to
      administer intravenous heparin to patients with diverse indications for oral
      anticoagulation (OAC) medications and how often these delays are potentially
      avoidable, as assessed by the prevalence of contraindications to outpatient use
      of low-molecular-weight heparin (LMWH). PATIENTS AND METHODS: Records were
      reviewed from a random sample of 309 patients who received at least 1 dose of OAC
      medication while hospitalized at the Mount Sinai Hospital in New York City
      between January 1 and December 31, 1997. Medical records were abstracted to
      determine admission diagnoses; patient demographics and comorbid conditions;
      indications for anticoagulation; laboratory data; and treatment and discharge
      medications, including whether LMWH was prescribed. A delay was defined as the
      continuation of hospitalization solely to administer intravenous heparin.
      Predefined criteria were used to classify the delay of discharge as appropriate
      or avoidable on the basis of the patient's potential eligibility for outpatient
      treatment with LMWH. RESULTS: Discharge was delayed for 75 of 309 patients (24%;
      95% confidence interval [CI], 19%-29%); during analysis of the avoidability of
      delay, 67 of the 75 medical records were available and showed that 32 of 67
      delays (48%; 95% CI, 35%-60%) were avoidable. Of patients taking long-term OAC
      medications who were admitted for reasons unrelated to thromboembolism or
      bleeding, discharge was delayed for 18 of 146 (12%; 95% CI, 7%-19%); during
      analysis of the avoidability of delay, 16 of the 18 medical records were
      available and showed that 9 of 16 delays (56%; 95% CI, 30%-80%) were avoidable.
      Of patients admitted for acute venous thromboembolism who were not taking long
      term OAC medications, discharge was delayed for 24 of 38 (63%; 95% CI, 46%-78%);
      during analysis of the avoidability of delay, 22 of the 24 medical records were
      available and showed that 11 of 22 delays (50%; 95% CI, 28%-72%) were avoidable.
      CONCLUSIONS: For patients taking OAC medications, hospital discharge is
      frequently delayed so that intravenous heparin can be administered; approximately
      half of these delays could be avoided by outpatient use of LMWH. Studies of the
      safety, efficacy, and feasibility of outpatient use of LMWH for indications other
      than deep venous thrombosis are needed because timely discharge of these patients
      could substantially decrease health care costs.

PMID- 14959909
TI  - Sensitivity and specificity of the semiquantitative latex agglutination D-dimer
      assay for the diagnosis of acute pulmonary embolism as defined by computed
      tomographic angiography.
AB  - OBJECTIVE: To determine the sensitivity and specificity of the semiquantitative
      latex agglutination plasma fibrin D-dimer assay for the diagnosis of acute
      pulmonary embolism by using computed tomographic (CT) angiography as the
      diagnostic reference standard. PATIENTS AND METHODS: From January 1, 1998, to
      June 26, 2000, patients who had both semiquantitative latex agglutination plasma
      fibrin D-dimer testing and CT angiography for suspected acute pulmonary embolism
      were selected for the study. A D-dimer value greater than 250 ng/mL was
      considered positive for thromboembolic disease. Diagnosis of acute pulmonary
      embolism was based solely on the interpretation of the CT angiogram. The D-dimer
      assay results were then compared with the CT angiographic diagnoses. RESULTS: Of
      946 CT studies, 172 (18%) were positive for acute pulmonary embolism. The D-dimer
      assay was positive for 612 (65%) of the 946 patients. For acute pulmonary
      embolism, the D-dimer assay had a sensitivity of 0.83 (95% confidence interval
      [CI], 0.76-0.88), a specificity of 039 (95% CI, 036-0.43), a negative likelihood
      ratio of 0.44 (95 % CI, 032-0.62), and a negative predictive value of 0.91 (95%
      CI, 0.87-0.94). CONCLUSIONS: The semiquantitative latex agglutination plasma
      fibrin D-dimer assay had moderate sensitivity and low specificity for the
      diagnosis of acute pulmonary embolism. When used alone, the results of this test
      were insufficient to exclude this serious and potentially fatal disorder.
      Approximately two thirds of our patients had positive D-dimer assays and required
      further evaluation to exclude acute pulmonary embolism.

PMID- 14959910
TI  - Therapeutic options in patients with lymphoma and severe liver dysfunction.
AB  - OBJECTIVES: To determine the long-term outcome of patients presenting with
      synchronous lymphoma and severe liver dysfunction and to describe the outcome of
      patients treated with initial mechlorethamine-based therapy used as a bridge to
      more conventional chemotherapy. PATIENTS AND METHODS: We reviewed the clinical
      course of all patients diagnosed as having lymphoma who presented with severe
      liver dysfunction and received intravenous mechlorethamine between September 1988
      and February 2003 at the Mayo Clinic in Rochester, Minn. RESULTS: Forty-one
      patients were identified, 33 (80%) of whom had newly diagnosed, previously
      untreated lymphoma. Thirty-seven (90%) had non-Hodgkin lymphoma, and 4 (10%) had
      Hodgkin disease. Thirty-four patients (83%) had stage IV disease, and 31 (84%) of
      37 had an intermediate-high International Prognostic Index. The median total
      bilirubin level before therapy was 10.7 mg/dL (range, 2.5-30.2 mg/dL), and the
      median alkaline phosphatase level was 982 U/L (range, 233-3415 U/L). In addition
      to mechlorethamine, 34 patients (83%) received concomitant corticosteroids, and
      12 (29%) received concomitant rituximab. Twenty-two patients (54%) had sufficient
      improvement in liver function to receive subsequent standard chemotherapy. Nine
      patients (22%) are alive and disease-free at a median of 31 months (range, 4 to >
      or = 87 months) after mechlorethamine treatment. Factors associated with improved
      overall survival included improvement in bilirubin levels (P < .001) and
      receiving subsequent standard chemotherapy (P = .001). CONCLUSION:
      Mechlorethamine, high-dose corticosteroids, and rituximab are useful therapeutic
      interventions for this unique group of patients with lymphoma and severe liver
      dysfunction. Substantial clinical improvement and long-term survival are
      possible.

PMID- 14959911
TI  - Acute aortic dissection: population-based incidence compared with degenerative
      aortic aneurysm rupture.
AB  - OBJECTIVES: To ascertain whether acute aortic dissection (AAD) remains the most
      common aortic catastrophe, as generally believed, and to detect any improvement
      in outcomes compared with previously reported population-based data. PATIENTS AND
      METHODS: We determined the incidence, operative intervention rate, and long-term
      survival rate of Olmsted County, Minnesota, residents with a clinical diagnosis
      of AAD initially made between 1980 and 1994. The incidence of degenerative
      thoracic aortic aneurysm (TAA) rupture was also delineated. We compared these
      results with other population-based studies of AAD, degenerative TAA, and
      abdominal aortic aneurysm (AAA) rupture. RESULTS: During a 15-year period, we
      identified 177 patients with thoracic aortic disease. We focused on 39 patients
      with AAD (22% of the entire cohort) and 28 with TAA rupture (16%). The annual age
      and sex-adjusted incidences were 3.5 per 100,000 persons (95% confidence
      interval, 2.4-4.6) for AAD and 3.5 per 100,000 persons (95% confidence interval,
      2.2-4.9) for TAA rupture. Thirty-three dissections (85%) involved the ascending
      aorta, whereas 6 (15%) involved only the descending aorta. Nineteen patients
      (49%) underwent 22 operations for AAD, with a 30-day case fatality rate of 9%.
      Among all 39 patients with AAD, median survival was only 3 days. Overall 5-year
      survival for those with AAD improved to 32% compared with only 5% in this
      community between 1951 and 1980. CONCLUSIONS: In other studies, the annual
      incidences of TAA rupture and AAA rupture are estimated at approximately 3 and 9
      per 100,000 persons, respectively. This study indicates that AAD and ruptured
      degenerative TAA occur with similar frequency but less commonly than ruptured
      AAA. Although timely recognition and management remain problematic, these new
      data suggest that recent diagnostic and operative advances are improving long
      term survival in AAD.

PMID- 14959912
TI  - Body esteem and mood among sedentary and active breast cancer survivors.
AB  - OBJECTIVES: To assess mood states and body esteem in 2 groups of breast cancer
      survivors, regular exercisers and sedentary women, and to examine these variables
      among younger and older women in each group. PATIENTS AND METHODS: Between 1998
      and 2002, we conducted a cross-sectional study among early-stage breast cancer
      survivors at the Miriam Hospital in Providence, RI, comparing 40 women who
      reported regular exercise with 79 sedentary women. We used multivariate and
      univariate analyses to compare the exercisers with sedentary women on fitness,
      physical activity, and questionnaire measures of body esteem and mood. Analyses
      were repeated after the 2 groups were subdivided by age (< 50 years vs > or = 50
      years). RESULTS: Regular exercisers (mean +/- SD age, 54.57 +/- 9.18 years)
      reported significantly more positive attitudes toward their physical condition
      and sexual attractiveness; significantly less confusion, fatigue, depression, and
      total mood disturbance; and higher vigor than sedentary women (mean +/- SD age,
      52.33 +/- 9.11 years). Both younger and older exercisers had higher physical
      condition scores than their sedentary peers. Older exercisers reported higher
      vigor and less confusion, anger, fatigue, depression, and total mood disturbance
      than sedentary women, regardless of age. Younger exercisers reported higher vigor
      than their sedentary peers and less confusion than older sedentary women.
      CONCLUSIONS: In this largely white sample of well-educated women, breast cancer
      survivors who exercised (particularly older women) reported higher body esteem
      and better mood than sedentary breast cancer survivors.

PMID- 14959913
TI  - Breast peau d'orange from large cell lymphoma.

PMID- 14959914
TI  - Controversies and legal issues of prescribing and dispensing medications using
      the Internet.
AB  - Online pharmacies fall into 3 major categories: independent Internet-only sites,
      online branches of "brick-and-mortar" pharmacies, and sites representing
      partnership among neighborhood pharmacies. Potential benefits of online
      pharmacies include increased access, lower transaction and product costs, and
      greater anonymity. However, online pharmacies have generated controversies,
      including the use of "cyberdoctors" on some sites, the dispensing of drugs
      without prescriptions from other sites, and the importation of prescription
      medications. Although some online pharmacies are legitimate and likely provide
      benefits to patients, other online pharmacies engage in questionable practices.
      Numerous state and federal regulations and laws have tried to address
      controversies surrounding rogue Internet pharmacies. Because online pharmacies
      are increasingly common, clinicians may encounter patients asking for advice and
      information about online pharmacies. We review the regulatory framework governing
      online pharmacies and the potential risks and benefits of using online
      pharmacies.

PMID- 14959915
TI  - Genetic determinants of arterial calcification associated with atherosclerosis.
AB  - Increasing research interest has focused on arterial calcification in the setting
      of atherosclerosis. Many features of atherosclerosis-related calcification
      provide useful clinical information. For example, calcium mineral deposits
      frequently form in atherosclerotic plaque, and intimal arterial calcification can
      be used as a surrogate marker for atherosclerosis; also, calcium deposits are
      readily and noninvasively quantified, which is useful because greater amounts of
      coronary calcification predict a higher risk of myocardial infarction and death.
      Several mechanisms leading to calcification associated with atherosclerosis have
      been proposed; however, no direct testing of proposed mechanisms has yet been
      reported. Studies in genetically altered animals and in humans have shed light on
      potential genetic determinants, which in turn could form the basis for a more
      comprehensive understanding of the factors affecting calcification within plaque
      and the associated pathobiologic implications. We review proposed molecular and
      cellular mechanisms of atherosclerosis-associated arterial calcification,
      summarize genetic influences, and suggest areas in which further investigation is
      needed. Understanding the molecular and genetic determinants of specific
      structural plaque components such as calcification can provide a solid foundation
      for the development of novel therapeutic approaches to favorably alter plaque
      structure and minimize vulnerability to arterial rupture.

PMID- 14959916
TI  - Contrast nephropathy after coronary angiography.
AB  - Contrast nephropathy after coronary angiography is associated with considerable
      morbidity and mortality. We discuss the incidence, definition, and pathologic
      mechanisms of contrast nephropathy; provide an overview of risk factors;
      highlight proven preventive interventions; clarify which interventions have shown
      no benefit; and discuss future possibilities. The prevention of contrast
      nephropathy is crucial for the care of patients undergoing coronary angiography
      and should be possible with an understanding of risk factors and proven
      management strategies.

PMID- 14959917
TI  - The preoperative cerebrovascular consultation: common cerebrovascular questions
      before general or cardiac surgery.
AB  - All types of health care providers may be called on to evaluate the risk of
      ischemic stroke related to an upcoming surgical procedure, particularly in
      patients with established cerebrovascular disease. We outline possible mechanisms
      contributing to perioperative stroke, summarize available data on the stroke risk
      associated with selected surgeries, and highlight recognized risk factors. We
      then provide recommended answers to some of the questions commonly encountered at
      the preoperative cerebrovascular consultation: What is the appropriate time
      interval between a stroke and elective surgery? What is the perioperative stroke
      risk for patients with established carotid or vertebrobasilar large artery
      stenosis, and what are the cardiac implications of detecting a cerebrovascular
      large artery stenosis? Should patients with a large artery stenosis undergo
      prophylactic revascularization procedures before undergoing general surgery? What
      treatment is appropriate for patients with both coronary artery and carotid or
      vertebrobasilar large artery stenosis? What is the appropriate perioperative
      management of antiplatelet and anticoagulant medications with respect to stroke
      risk?

PMID- 14959918
TI  - 18-year-old woman with headache and sore throat.

PMID- 14959919
TI  - Glomus tumor of the trachea: value of multidetector computed tomographic virtual
      bronchoscopy.
AB  - Glomus tumor of the trachea is extremely rare. We report a case of tracheal
      glomus tumor in a 39-year-old man who presented with hemoptysis. The diagnosis
      was made after bronchoscopic biopsy of a tumor involving the posterior wall of
      the upper trachea. Thin-section multidetector computed tomography of the chest
      was performed before surgical resection, with multiplanar re-formations and 3
      dimensional virtual bronchoscopic reconstruction. Tracheal sleeve resection with
      reconstruction was successful, and pathological studies confirmed complete
      resection and the diagnosis of glomus tumor. The patient was disease-free 3
      months postoperatively. To our knowledge, this is the first reported case in
      which additional computed postprocessing was used to help evaluate the extent of
      such a tumor.

PMID- 14959920
TI  - Pneumocystis carinii pneumonia in a 3-month-old infant receiving high-dose
      corticosteroid therapy for airway hemangiomas.
AB  - Primary infection with Pneumocystis carinii usually occurs early in life, and
      young infants receiving prolonged treatment with high-dose corticosteroids may be
      at risk for the development of symptomatic disease. Prophylaxis with trimethoprim
      sulfamethoxazole is safe and effective and should be considered for such infants,
      particularly those with underlying airway abnormalities. We describe a 3-month
      old immunocompetent infant who developed severe P carinii pneumonia after 6 weeks
      of high-dose corticosteroid therapy for cervicofacial and airway hemangiomas.

PMID- 14959921
TI  - Gram-negative cellulitis complicating cirrhosis.
AB  - Gram-negative infections are common in patients with cirrhosis, but skin
      infections are usually caused by gram-positive cocci. Gram-negative bacteria
      should be considered as a potential etiologic agent in patients with cirrhosis
      and severe bullous cellulitis. Culture of the bullous fluid may facilitate
      diagnosis and management. Early recognition is important because the course of
      the disease is usually rapid and fatal. We report 4 cases of fulminant gram
      negative bullous cellulitis and septic shock in patients with cirrhosis.

PMID- 14959922
TI  - Q fever endocarditis in the United States.
AB  - Infections due to Coxiella burnetii, the causative organism of Q fever, are
      extremely rare in North America. Endocarditis due to the organism has an unusual
      presentation and poses echocardiographic and laboratory challenges in
      establishing a diagnosis. We describe the presentation and clinical course of a
      40-year-old American man with Q fever endocarditis and briefly discuss the
      salient issues regarding this entity.

PMID- 14959923
TI  - Wound care for elderly patients: advances and clinical applications for
      practicing physicians.
AB  - Chronic ulcers (wounds) are commonly encountered in medical practice,
      particularly in elderly patients who have chronic medical conditions. Health care
      providers must be adept at diagnosing chronic ulcers and optimizing medical
      treatment. We describe the best medical practice for the 4 common types of
      chronic ulcers: pressure ulcers, ischemic ulcers, venous ulcers, and neuropathic
      ulcers. We emphasize the importance of nutrition and proper wound care as a
      foundation for the management of all chronic ulcers. There is a unique
      therapeutic goal for each chronic ulcer. Pressure relief should be provided for
      both pressure ulcers and neuropathic ulcers. Ischemic ulcers require
      revascularization. Patients with venous ulcers need adequate edema control. We
      outline advances in each of these areas and discuss the newest developments in
      wound care, including growth factors, hyperbaric oxygen, and vacuum-assisted
      devices. Chronic ulcers in elderly patients can heal with proper diagnosis and
      good medical care.

PMID- 14959924
TI  - Half a century of visual pattern-sensitive epilepsy.

PMID- 14959925
TI  - Brugada-type electrocardiographic pattern unmasked by fever.

PMID- 14959926
TI  - The message is not the median!

PMID- 14959927
TI  - Radiotherapy for MALT lymphoma.

PMID- 14959928
TI  - Foreign object ingestion.

PMID- 14959929
TI  - Brain temperature in patients with chronic hydrocephalus after subarachnoid
      hemorrhage.
AB  - The relationships between temperature indices and clinical condition on admission
      or improvement after ventriculoperitoneal (VP) shunting were evaluated in
      patients with subarachnoid hemorrhage (SAH). Brain temperatures were measured at
      intervals of 1 cm from the brain surface to the lateral ventricle at shunt
      operation. Rectal temperature was also measured. The difference between
      intraventricular and rectal temperatures was correlated with age (p = 0.0486),
      Glasgow Coma Scale (p = 0.0129), Hunt and Hess grade (p = 0.0101), and
      improvement score after VP shunting (p = 0.0104). Measurement of brain
      temperature may predict the outcome of VP shunting in patients with SAH.

PMID- 14959930
TI  - Simulation of clipping position for cerebral aneurysms using three-dimensional
      computed tomography angiography.
AB  - A novel method for the simulation of the clipping position for cerebral aneurysms
      based on three-dimensional computed tomography (3D CT) angiography was evaluated.
      Rotating the regional 3D CT angiography images including the aneurysm provided
      the virtual intraoperative views of 36 cerebral aneurysms that were eligible for
      clipping through a pterional approach with a perpendicularly applied straight
      clip. The cut-along-trace function of the 3D CT workstation was used to simulate
      the clipping position. The presence or absence of aneurysm remnants was
      preoperatively evaluated by observing the clipping simulation image.
      Intraoperative endoscopy and postoperative cerebral angiography were routinely
      performed to confirm the completeness of obliterations. Nineteen of 21 aneurysms
      for which complete obliteration was preoperatively expected were confirmed to
      have no aneurysm remnant. Nine of 15 aneurysms which were expected to have
      aneurysm remnant were confirmed to persist. The clipping simulation images could
      correctly predict aneurysm remnant after the initial clipping with a sensitivity
      of 90.5% and specificity of 60%. The present simulation method can predict
      aneurysm remnants and improve the likelihood of complete obliteration by
      clipping.

PMID- 14959931
TI  - Investigation of two possible compression sites of the deep branch of the radial
      nerve and nerve supply of the extensor carpi radialis brevis muscle.
AB  - The posterior interosseous nerve arises from the deep branch of the radial nerve,
      and compression by adjacent structures results in posterior interosseous nerve
      syndrome. Sixty upper limbs from 30 Turkish subjects (18 males and 12 females)
      were dissected to reveal the course of the posterior interosseous nerve and to
      examine possible compression sites at the proximal and distal edges of the
      supinator muscle, and the exit of the nerve from the extensor carpi radialis
      brevis muscle. Posterior interosseous nerve syndrome is most probably caused by
      the tendinous part of the supinator muscle at the proximal edge.

PMID- 14959932
TI  - Ruptured saccular aneurysm of a dolichoectatic internal carotid artery in a
      patient with agenesis of the contralateral internal carotid artery--case report.
AB  - A 42-year-old woman presented with very rare cases of ruptured saccular aneurysm
      of a dolichoectatic internal carotid artery (ICA) associated with agenesis of the
      contralateral ICA manifesting as sudden onset of severe headache and nausea
      without neurological deficits. Angiography and three-dimensional computed
      tomography demonstrated intraventricular hemorrhage with slight subarachnoid
      hemorrhage and dolichoectasia of the right ICA with agenesis of the contralateral
      ICA, as well as a saccular aneurysm of the ectatic right ICA. The aneurysm neck
      was clipped successfully. The patient remained ambulatory with no neurological
      deficits at discharge 15 days after the surgery. The saccular aneurysm in our
      case was formed in the dolichoectatic ICA, presumably due to both abnormal
      hemodynamics and abnormal arterial wall.

PMID- 14959933
TI  - Intracranial dural arteriovenous fistula with venous reflux to the brainstem and
      spinal cord mimicking brainstem infarction--case report.
AB  - A 73-year-old man presented with a rare transverse sinus dural arteriovenous
      fistula (dAVF) with venous reflux to the brainstem and medulla manifesting as
      brainstem and spinal cord edema mimicking brainstem infarction. Complete
      occlusion of the fistula was achieved by transvenous embolization, resulting in
      angiographic cure of the fistula and progressive improvement of the symptoms.
      Intracranial dAVFs with perimedullary venous drainage, type V according to the
      Cognard classification, are rare lesions with distinctive clinical, radiological,
      and therapeutic aspects. This case demonstrates that the symptoms of dAVF with
      perimedullary venous reflux are variable, so dAVF should be considered in
      patients with clinical and radiological findings suggestive of congestion in the
      brainstem and spinal cord. Dysfunction of the medulla and spinal cord caused by
      venous hypertension is the most probable cause of the neurological symptoms in
      such cases. Interventional therapy can lead to angiographic cure and resolution
      of the symptoms.

PMID- 14959934
TI  - Intracranial osteosarcoma after radiosurgery--case report.
AB  - A 56-year-old woman presented with an intracranial osteosarcoma at the site of
      previous radiosurgery, manifesting as sudden onset of headache and left
      hemiparesis with aphasia. She had a previous history of stereotactic radiosurgery
      for an intracranial tumor under a diagnosis of falx meningioma. Computed
      tomography showed intratumoral and peritumoral hemorrhage at the right
      parietofrontal region. Gross total resection of the tumor with hematoma was
      performed. The histological diagnosis was osteosarcoma. Sarcomatous change is a
      rare complication of radiotherapy. This case illustrates that osteosarcoma may
      develop years after radiosurgery for benign brain neoplasm.

PMID- 14959935
TI  - Growing teratoma syndrome in a patient with a non-germinomatous germ cell tumor
      in the neurohypophysis--case report.
AB  - A 16-year-old woman presented with a non-germinomatous germ cell tumor in the
      neurohypophysis manifesting as progressive visual disturbance, amenorrhea,
      hydrodipsia, and polyuria. Her serum alpha-fetoprotein and human chorionic
      gonadotropin levels were elevated. She experienced sudden, rapid visual
      deterioration and underwent emergency partial tumor removal to decompress the
      optic nerves. Her vision subsequently improved. Histological examination of the
      surgical specimens confirmed immature teratoma. She received chemotherapy
      (ifosphamide 900 mg/m2, cisplatin 20 mg/m2, etoposide 60 mg/m2) for 5 consecutive
      days. Although the tumor marker levels decreased remarkably, her vision again
      declined rapidly due to enlargement of the tumor after the first course of
      chemotherapy. A second radical operation resulted in vision improvement. The
      tumor specimen showed only mature teratoma elements. This phenomenon, called the
      growing teratoma syndrome, is very rare in intracranial non-germinomatous germ
      cell tumors.

PMID- 14959936
TI  - Malignant peripheral nerve sheath tumor in the anterior skull base associated
      with neurofibromatosis type 1--case report.
AB  - A 36-year-old man presented with a tumor in the anterior skull base manifesting
      as headache and visual disturbance. Neurofibromatosis type 1 (NF-1) was
      identified in early childhood in the patient, and also in his father. Subtotal
      excision of the tumor was performed, leaving the portion extending outside of the
      cranium. The histological diagnosis was malignant peripheral nerve sheath tumor.
      Local radiotherapy was instituted postoperatively. Facial paralysis and dysphagia
      appeared 7 months after the first operation. Magnetic resonance imaging revealed
      new lesions in the lateral ventricle and around the brainstem. These tumors were
      also subtotally excised, but the patient died 10 months after the first
      operation. The tumor very likely originated from the meningeal branch of the
      trigeminal nerve. Treatment of such tumors developing inside the cranium should
      include the widest resection possible, followed by irradiation of the entire
      neuraxis including the spinal cord to inhibit dissemination through the
      cerebrospinal fluid. Treatment should be started as quickly as possible if the
      tumor is associated with NF-1, because of the poor prognosis associated with this
      condition.

PMID- 14959937
TI  - Craniopharyngiomas with intratumoral hemorrhage--two case reports.
AB  - Two cases of craniopharyngioma with intratumoral hemorrhage are reported. A 22
      year-old male was admitted with meningitis. Lumbar tapping was performed twice.
      He subsequently developed reduced visual acuity and field deterioration due to
      intratumoral hemorrhage from an intra- and suprasellar tumor. He underwent
      emergency craniotomy and total extirpation of the tumor. A 29-year-old female
      underwent partial extirpation of an intra- and suprasellar cystic tumor via
      transsphenoidal surgery. Two months after the first operation, she suffered
      intratumoral hemorrhage necessitating emergency surgery and subsequent gamma
      knife therapy. The histological diagnosis was craniopharyngioma in both cases.
      Hemorrhage is extremely rare in craniopharyngiomas and difficult to discriminate
      from that in pituitary adenoma, but both diseases require decompression by clot
      extirpation.

PMID- 14959938
TI  - Metastatic pituitary tumor from renal cell carcinoma treated by fractionated
      stereotactic radiotherapy--case report.
AB  - A 63-year-old man presented with rapidly progressive visual field deficit and
      hypopituitarism including diabetes insipidus, 8 years after treatment for a renal
      cell carcinoma. Neuroimaging studies revealed a dumbbell-shaped pituitary mass
      that had destroyed the sellar floor and abutted against the optic apparatus.
      Fractionated stereotactic radiotherapy (SRT), employing computer-image
      integration techniques and a frame that could be relocated to facilitate a
      fractionated dosing scheme, was carried out under a plan for reducing the
      treatment risk to the optic apparatus. Three months later, the patient exhibited
      marked improvement in the visual field deficit and visual acuity concomitant with
      a reduction in tumor volume. Magnetic resonance imaging of the sellar region
      confirmed striking shrinkage of the metastasis. His neurological status remained
      stable at 12 months after the SRT with no complications. Fractionated SRT appears
      to be effective for preserving or improving the residual vision in patients with
      visual loss secondary to metastatic tumor of the pituitary gland, and may result
      in a longer and better quality of life.

PMID- 14959939
TI  - Rosacea as an inflammatory disorder: a unifying theory?
AB  - Rosacea is increasingly being viewed as an immune-based disorder. Various immune
      factors, such as eicosanoids, proinflammatory cytokines, and polymorphonuclear
      leukocytes, appear to be involved in the vascular, inflammatory, and
      proliferative subtypes of this disorder. Many pharmacologic agents that
      effectively treat the symptoms of rosacea show anti-inflammatory and/or
      immunomodulating effects, providing further evidence that rosacea is an
      inflammatory disorder.

PMID- 14959940
TI  - The subtypes of rosacea: implications for treatment.
AB  - Lack of standardized rosacea nosology was the rationale for the National Rosacea
      Society to convene a committee of dermatology thought leaders to develop a
      standard classification system. Standardization of rosacea classification should
      be followed by standardization of treatment. Many pharmacologic and
      nonpharmacologic interventions for rosacea are being used based on clinical
      observation alone. Many oral and topical pharmacologic agents, however, are
      validated by randomized controlled trials (RCTs). Topical therapies (eg,
      metronidazole or an alternative agent such as azelaic acid) and oral antibiotics
      (eg, the tetracycline family) should remain as foundation therapies for subtypes
      1 and 2 rosacea, based on the strength of the evidence.

PMID- 14959941
TI  - Mechanism-based selection of pharmacologic agents for rosacea.
AB  - All effective agents used to treat rosacea have a common mechanism of action:
      anti-inflammatory effects. Concomitant with this, many of these agents also show
      antioxidant effects. Both anti-inflammatory and antioxidant effects may address
      the proposed underlying pathophysiology of rosacea. Future topical formulations
      may involve the combination of active pharmacologic agents and sunscreens or sun
      blocks to address the proposed etiologic role played by UV radiation in the
      pathophysiology of rosacea.

PMID- 14959942
TI  - The role of topical metronidazole in the treatment of rosacea.
AB  - Many topical and oral pharmacologic agents have shown well-tolerated efficacy for
      the treatment of rosacea. Metronidazole was the first topical therapy approved
      for rosacea and is still considered the foundation therapy by many researchers
      and dermatologists. The efficacy and tolerability of topical metronidazole in
      combination with an oral antibiotic or as monotherapy to maintain remissions have
      been shown in multiple well-controlled trials.

PMID- 14959943
TI  - Evaluating the role of topical therapies in the management of rosacea: focus on
      combination sodium sulfacetamide and sulfur formulations.
AB  - The combination of sodium sulfacetamide and sulfur is unique in the rosacea
      armamentarium because of its dual use as topical therapy and therapeutic
      cleanser. Several formulations of sulfacetamide 10% and sulfur 5% are now
      available as topical lotions and cleansers. The sulfacetamide/sulfur cleansers
      serve as adjunctive therapy by providing additive effects to other topical and
      oral therapies for rosacea with favorable tolerability and cosmetic appeal.

PMID- 14959944
TI  - The treatment of rosacea.
AB  - The roundtable discussion encompassed many topics-from seminal research by Ronald
      Marks to the latest National Rosacea Society-funded studies on the
      pathophysiology of rosacea. All participants commented on the value of the new
      National Rosacea Society classification system for subtypes of rosacea, designed
      to direct future research and help physicians better diagnose and manage these
      subtypes. A lively discussion centered on treatment options for the various
      subtypes of rosacea ensued.

PMID- 14959945
TI  - Japanese elderly cohort in Okinawa, Japan: exploring the relationship of social
      factors and health.

PMID- 14959946
TI  - Association of health behavior and social role with total mortality among
      Japanese elders in Okinawa, Japan.
AB  - BACKGROUND AND AIMS: Longitudinal studies on the relationship of life-style
      factors and social networking with mortality have been only slightly conducted in
      a comprehensive manner among the Japanese elderly. This study aims at examining
      associations of health behavior and social role with total mortality among
      Japanese elders in Okinawa. METHODS: All residents aged 65 years or older were
      recruited in 1987 from the village of Ohgimi, and 724 subjects were followed for
      12 years. A comprehensive health assessment questionnaire was used, and the
      resulting data were analyzed by the Cox proportional hazards model. RESULTS: The
      number of deaths during the study period was 139 (55.4%) for men and 166 (35.1%)
      for women. The standardized mortality rates of malignancy, cerebrovascular
      disease, heart disease and pneumonia were higher for men. In the final model of
      multivariate analysis for women, less than 6 hours of sleep [Hazard ratio
      (HR)=2.62] and lower social role (HR=1.88) significantly increased the risk of
      mortality. As for men, neither health behavioral items nor social role showed a
      significant association with mortality. CONCLUSIONS: Our study results suggest
      that having sufficient hours of sleep and enhancing social role could greatly
      help elderly women in Okinawa to maintain good health. Moreover, our study
      provides direction for future research to explore the difference in adequate
      health promotion measures between women and men.

PMID- 14959947
TI  - Are IADLs comparable across countries? Sociodemographic associates of harmonized
      IADL measures.
AB  - BACKGROUND AND AIMS: Independence in Instrumental Activities of Daily Living
      (IADLs) is determined not only by physical ability but also by the environmental
      and cultural surroundings of the individual. The present study describes the
      harmonization of data on IADL functioning of the Comparison of Longitudinal
      European Studies on Aging (CLESA) Project. The focus of this report is to examine
      the comparability of IADLs across countries and to study the association of IADLs
      with age, gender and socioeconomic status, and the scalability of the measure.
      METHODS: The study base includes data from five European countries (Finland,
      Italy, The Netherlands, Spain, Sweden) and Israel, for older people aged 65-89
      living both in the community and in institutions, for a total of 11,557 subjects.
      In this report, only community-dwelling respondents were included (N=8420). The
      common IADL items in all six countries were: preparing meals, shopping, and doing
      housework. The analyses include how these items are distributed by age group and
      gender, and the associations between independence in these items and
      socioeconomic status (SES) with logistic regression modeling. The scale
      properties of these three items are also examined. RESULTS: Independence in IADLs
      decreases steadily with age in all countries. Associations with gender and SES
      follow largely similar patterns across countries. The reliability of the 3-item
      scale is satisfactory in most countries, and Cronbach's alpha-coefficient for the
      complete CLESA sample was 0.75. CONCLUSIONS: The associations between
      sociodemographic variables and independence in preparing meals, shopping, and
      doing housework are similar across countries. Results suggest that the predictors
      of IADLs in different countries are comparable.

PMID- 14959948
TI  - Nutrient intake and growth characteristics of male Sprague-Dawley rats fed AIN
      93M purified diet or NIH-31 natural-ingredient diet in a chronic two-year study.
AB  - BACKGROUND AND AIMS: Daily nutrient intake and growth of male Sprague-Dawley (SD)
      rats fed compositionally different diets were monitored over 114 weeks to
      determine whether rats fed ad libitum (AL) or diet restricted (DR) followed
      normal growth parameters. A second objective was to evaluate the usefulness of
      the American Institutes of Nutrition's AIN-93M (maintenance formulation) diet for
      aging and DR studies. METHODS: Rats were fed NIH-31 cereal-based diet AL, or a
      vitamin-fortified modification of the NIH-31 diet at 10, 25, or 40% DR. Other SD
      rats were fed AIN-93M diet AL or 31% DR; daily nutrient intake and growth
      response were reported. RESULTS: At all intervals up to 36 weeks of age, rats fed
      AL the NIH-31 diet consumed significantly (p<0.001) more than rats fed AL the AIN
      93M diet, and required more diet per unit of gain than AIN-93M AL rats. However,
      body weight (BW) gain in rats AL-fed the AIN-93M diet demonstrated that energy
      components were more efficiently metabolized than in those fed the NIH-31 diet.
      Whereas diet restriction decreased BW, the rate of maturation, i.e., the rate of
      reaching a mature BW, increased as intake level decreased. Growth response showed
      all growth curves were normal, but intake level effects on mature BW and
      maturation rate differed significantly (p<0.001). Curves for rats AL- and DR-fed
      the AIN-93M diets were similar to those of rats AL- and DR-fed NIH-31 diet
      formulations, suggesting that diets adequately met growth requirements and
      supported normal growth parameters of male SD rats when fed AL or DR.
      CONCLUSIONS: A modification in the AIN-93M energy components to reduce total
      calories and an evaluation of other nutrient profiles could improve its
      usefulness as a maintenance and aging diet.

PMID- 14959949
TI  - Imbalance of pro- and anti-inflammatory cytokine responses in elderly patients
      after coronary artery bypass grafting.
AB  - BACKGROUND AND AIMS: Increased inflammatory activity has been observed in elderly
      people. The aim of this study was to determine whether cytokine responses after
      coronary artery bypass grafting (CABG) in elderly patients are different from
      those in younger patients. METHODS: Fifty-five male patients admitted for first
      time elective coronary artery bypass surgery were divided into two age groups:
      group I, patients younger than 70 years (N=40); and group II, patients aged 70
      years or older (N=15). Perioperative levels of cytokines and CK-MB were measured.
      Hemodynamic data were recorded. RESULTS: Marginally higher IL-6 (p=0.048) and IL
      8 (p=0.041) levels were observed during the intensive care unit (ICU) stay in the
      elderly as compared with younger patients. Lower IL-10 levels were detected in
      the elderly 5 minutes after reperfusion to the myocardium (p<0.05). Although the
      postoperative hemodynamic change was similar in both groups, the elderly needed
      vasopressor treatment more often during the ICU stay. This was associated with
      lower IL-10 levels 5 minutes after reperfusion. CONCLUSIONS: The present results
      show the age-related imbalance of pro- and anti-inflammatory responses after
      CABG, associated with hemodynamic instability in the elderly.

PMID- 14959950
TI  - Voluntary exercise and mild food restriction effectively retard the collagen
      biomarker of aging.
AB  - BACKGROUND AND AIMS: Obesity and lack of physical exercise characterize
      increasing numbers of people in Western societies, resulting in increasing
      morbidity and mortality. Regular physical exercise, on the other hand, has been
      shown to be beneficial. Beneficial effects have also been shown in laboratory
      rodent studies--lifelong physical exercise increases the mean life span but not
      the maximum life span, while food restriction increases both life spans. We
      studied male Sprague-Dawley rats in order to further analyze these beneficial
      effects. METHODS: We compared voluntary running in wheels (RW) with food
      restriction to pair weight with RW (PW), and mild forced running in treadmill
      (TM)--all animals housed individually. Control groups were sedentary ad libitum
      fed animals housed individually (S1) and four to a cage (S4). The collagen
      biomarker of aging was calculated as a composite parameter from thermal stability
      data for 5 (baseline), 15, 19 and 23 months of age. RESULTS: In RW and PW, the
      increase in the composite parameter was retarded to the same extent. The
      retardation in TM was less efficient. S4 had the highest value for the composite
      parameter, together with the highest body weight and fat content. In groupwise
      comparisons, the composite parameter tended to predict survival in the groups up
      to the age of 23 months. CONCLUSIONS: Voluntary running in wheels is more
      beneficial than mild-forced exercise on the treadmill. The composite parameter is
      a useful indicator of different interventions on aging rats.

PMID- 14959951
TI  - Carotenoid and vitamin E status are associated with indicators of sarcopenia
      among older women living in the community.
AB  - BACKGROUND AND AIMS: Oxidative stress may play a role in the pathogenesis of
      sarcopenia, and the relationship between dietary antioxidants and sarcopenia
      needs further elucidation. The aim was to determine whether dietary carotenoids
      and alpha-tocopherol are associated with sarcopenia, as indicated by low grip,
      hip, and knee strength. METHODS: Cross-sectional analyses were conducted on 669
      non-disabled to severely disabled community-dwelling women aged 70 to 79 who
      participated in the Women's Health and Aging Studies. Plasma carotenoids and
      alpha-tocopherol were measured. Grip, hip, and knee strength were measured, and
      low strength was defined as the lowest tertile of each strength measure. RESULTS:
      Higher plasma concentrations of alpha-carotene, beta-carotene, beta
      cryptoxanthin, and lutein/zeaxanthin were associated with reduced risk of low
      grip, hip, and knee strength. After adjusting for potential confounding factors
      such as age, race, smoking, cardiovascular disease, arthritis, and plasma
      interleukin-6 concentrations, there was an independent association for women in
      the highest compared with the lowest quartile of total carotenoids with low grip
      strength [Odds Ratios (OR) 0.34, 95% Confidence Interval (CI) 0.20-0.59], low hip
      strength (OR 0.28, 95% CI 0.16-0.48), and low knee strength (OR 0.45, 95% CI 0.27
      0.75), and there was an independent association for women in the highest compared
      with the lowest quartile of alpha-tocopherol with low grip strength (OR 0.44, 95%
      CI 0.24-0.78) and low knee strength (OR 0.52, 95% CI 0.29-0.95). CONCLUSIONS:
      Higher carotenoid and alpha-tocopherol status were independently associated with
      higher strength measures. These data support the hypothesis that oxidative stress
      is associated with sarcopenia in older adults, but further longitudinal and
      interventional studies are needed to establish causality.

PMID- 14959952
TI  - ECG abnormalities in the elderly: prevalence, time and generation trends and
      association with mortality.
AB  - BACKGROUND AND AIMS: Electrocardiographic (ECG) abnormalities are often found in
      older patients but relatively few epidemiological studies have been performed.
      This study describes: a) cross-sectional differences in ECG abnormalities among
      three 70-year-old cohorts born over a period of 30 years; b) longitudinal changes
      in ECG abnormalities from the age of 70 to 85; and c) the relationship between
      ECG abnormalities at age 70 and subsequent 10- and 15-year mortality in men and
      women. METHODS: Trends in the prevalence of ECG abnormalities were investigated
      among 2100 70-year olds (994 men, 1106 women) from three cohorts born in 1901/02
      (I), 1911/12 (III) and 1930 (VI). Longitudinal changes and mortality risks were
      investigated among 973 70-year olds (449 men and 524 women) from cohort I, which
      was followed from 1971 until 2001. RESULTS: In both sexes, the prevalence of ECG
      abnormalities was significantly lower in the later-born cohorts. From age 70 to
      85, there was an increase in both men and women of large or intermediate Q-waves,
      left axis deviation, negative T-waves (0-5 mm), complete right bundle branch
      block (RBBB), and atrial fibrillation or flutter. Compared with those with no ECG
      abnormalities, the mortality risk was higher among individuals with large and
      intermediate Q-waves and negative T-waves (> or = 1 mm) in both sexes, and STJ
      depression > or = 0.5 mm and complete LBBB together with complete RBBB and
      intraventricular block; QRS > or = 0.12 sec in men only. CONCLUSIONS: ECG
      abnormalities are frequent in the elderly, they increase with age, and are
      associated with increased mortality.

PMID- 14959953
TI  - The risk of upper gastrointestinal bleeding in elderly users of aspirin and other
      non-steroidal anti-inflammatory drugs: the role of gastroprotective drugs.
AB  - BACKGROUND AND AIMS: Although the administration of gastroprotective drugs may
      reduce the risk of gastrointestinal (GI) bleeding due to intake of non-steroidal
      anti-inflammatory drugs (NSAIDs) and aspirin during chronic treatment, no
      consensus exists as to whether such co-therapy is effective in short-term
      prevention, particularly in old age. The aim of our study was to evaluate the
      risk of bleeding associated with acute and chronic NSAID or aspirin therapy in
      elderly subjects, and the influence of gastroprotective treatment on such a risk.
      METHODS: The study included 467 elderly NSAID or aspirin users and 1784 non
      users, who consecutively underwent upper GI endoscopy. The use of NSAIDs and/or
      aspirin as well as gastroprotective drugs (misoprostol, H2-blockers, proton pump
      inhibitors) was evaluated during a structured interview. Upper GI tract bleeding
      was diagnosed on the basis of symptoms and endoscopic signs of recent hemorrhage.
      RESULTS: 54.2% of patients were acute and 45.8% chronic users of NSAIDs or
      aspirin. The risk of bleeding was higher in acute [odds ratio (OR) 4.14, 95% CI
      2.97-5.78] than chronic users (OR 1.71, 95% CI 1.1-2.67). The risk of bleeding,
      adjusted for age, gender, Helicobacter (H) pylori infection, and gastroprotective
      drug use were 7.87 (CI 4.90-12.60) in acute users and 3.97 (95% CI 2.27-6.96) in
      chronic users of NSAIDs and/or aspirin. The risk of bleeding was significantly
      associated with acute but not chronic use of regular-dose aspirin (OR 5.53, 95%
      CI 2.29-13.3), diclofenac (OR 4.44, 95% CI 2.21-8.93), ketorolac (OR 4.81, 95% CI
      2.13-10.9), naproxen (OR 14.9, 95% CI 4.23-52.4) or nimesulide (OR 4.06, 95% CI
      1.2-13.8). Piroxicam increased the risk of bleeding in both acute (OR 5.36, 95%
      CI 1.94-14.8) and chronic therapy (OR 5.53, 95% CI 1.23-24.9). In acute users,
      concomitant therapy with proton pump inhibitors reduced the risk of bleeding
      compared with non-users (OR 1.05, 95% CI 0.19-5.65), whereas co-treatment with H2
      blockers was associated with a significantly higher risk of bleeding than in non
      users (OR 3.40, 95% CI 1.28-9.02). Chronic users of NSAIDs or aspirin co-treated
      with proton pump inhibitors had a lower risk of bleeding (OR 1.12, 95% CI 0.21
      6.07) than those treated with misoprostol (OR 1.91, 95% CI 0.33-10.9) or H2
      blockers (OR 2.26, 95% CI 0.81-6.36). CONCLUSIONS: The risk of upper GI bleeding
      is significantly higher in elderly acute vs chronic users of NSAIDs or regular
      dose aspirin. In acute NSAID or aspirin users, co-treatment with proton pump
      inhibitors, but not with H2-blockers, may reduce the risk of bleeding compared
      with non-users.

PMID- 14959954
TI  - A single bisphosphonate infusion is associated with improved functional capacity
      in elderly subjects with primary hyperparathyroidism.
AB  - BACKGROUND AND AIMS: Neuromuscular symptoms are frequent features of primary
      hyperparathyroidism in elderly patients. Whether these symptoms are related to
      concomitant disorders or to hypercalcemia is of major importance in selecting
      patients who could benefit by parathyroidectomy. To address this hypothesis, we
      investigated the effects of transient normalization of calcemia on functional
      capacity by the administration of a single infusion of the bone resorption
      inhibitors pamidronate or clodronate. METHODS: Functional capacity was evaluated
      by the functional independence measure (FIM) in 25 patients aged 87.1+/-0.8 years
      (means+/-SEM) with primary hyperparathyroidism. Nine patients aged 88.4+/-1.1
      with primary hyperparathyroidism, not receiving any bisphosphonate, were used as
      controls. RESULTS: By inhibiting bone resorption, bisphosphonate administration
      caused transient normalization of calcemia, associated with improved FIM, at a
      significantly higher level than in untreated patients (+16.1+/-6.0 vs +4.2+/
      3.2%, p<0.05). CONCLUSIONS: If confirmed in a randomized prospective study, these
      results indicate that a single bisphosphonate infusion, with consecutive
      transient improvement of functional capacity in relation to plasma calcium
      normalization, could help in identifying elderly patients who would benefit by
      parathyroidectomy.

PMID- 14959955
TI  - Impact of fractures on health care in a major university hospital in Rome.
AB  - BACKGROUND AND AIMS: The aim of the study was to investigate the impact of
      fractures (i.e., hip, Colles, humeral and vertebral fractures), compared with
      that of other common diseases requiring hospitalization, on health care in the
      main hospital in Rome (Italy). METHODS: Hospital discharge forms, filled in
      according to the 9th International Classification of Diseases, were examined from
      1996 to 1999. Data on fractures were compared with those related to other
      diseases which occupy a considerable proportion of hospital operating time in
      Italy: coronary heart disease (CHD), cerebrovascular disorders (CVD), diabetes
      mellitus (DM), chronic obstructive pulmonary disease (COPD) and breast cancer
      (BC). RESULTS: In all groups of patients, the mean age of females was
      significantly higher (p<0.0001) than that of males. Male patients with hip
      fractures had hospital stays significantly longer than females (p<0.0001),
      whereas women with Colles fractures had significantly (p<0.02) longer stays. When
      patients were divided according to age (i.e., over or under 60 years), mean
      hospital stays did not differ between younger and older patients in all groups
      except Colles fractures (p<0.001). Hip fractures in older patients showed
      striking in-hospital mortality. Throughout the study period, hip fractures
      accounted for the highest overall and per-patient costs. The number of female
      patients with fractures (and, obviously, breast cancer) was higher, while the
      opposite applied to the other disorders. Male patients with fractures, CHD and
      CVD were significantly younger than females (p<0.0001). When the percentage of
      deaths was added to that of patients discharged to other institutions, fractures
      showed the poorest outcome of any hospitalization event. Per-patient costs were
      remarkably higher for CHD, followed by fractures. CONCLUSIONS: Fractures
      represent a growing but often underestimated burden for hospital care in Italy;
      further studies are needed on this issue.

PMID- 14959956
TI  - The significance of social network in a geriatric assessment population.
AB  - BACKGROUND AND AIMS: There has long been speculation that socially-involved
      individuals suffer less illness, overcome sickness more readily, and experience
      better health outcomes than more socially isolated persons. This study describes
      social network characteristics, and determines whether social network affects
      health outcomes in the geriatric population. METHODS: Data from 1270 consecutive
      patients seen in the outpatient Geriatric Assessment Clinic (GAC) of the
      University of Nebraska Medical Center between August 1988 and May 1999 were
      analyzed. Social network was measured by the Social Network Index (SNI). RESULTS:
      Younger age, higher income and higher education were related to a broader social
      network. A larger social network was generally associated with lower caregiver
      burden, higher functional status and better cognition. Men with the smallest
      social networks were found to be at significantly higher risk of death than women
      with larger social networks (HR 4). After adjusting for age (HR 1.04, CI 1.03
      1.06), income (HR 1.00, CI 1-1), education (HR, NS), IADL (HR 0.97, CI 0.95
      0.99), CIRS (HR 1.08, CI 1.05-1.10) and informal service use (HR, NS), the risk
      of death for subjects based on SNI is only significant in the comparison between
      SNI III and SNI I (HR 0.67, CI 0.50-0.91). CONCLUSIONS: SNI I males are at
      significantly increased risk of death compared with all other groups. The average
      number of years from initial visit to death for SNI I males is only 2.8 years.
      These results are consistent with the literature, which suggests men are more
      affected by social isolation and have decreased survival compared with females.
      The influence of SNI on mortality in this frail, elderly group appears to be
      diluted by the presence of functional disability and a high degree of comorbid
      illness.

PMID- 14959957
TI  - Charles-Bonnet syndrome exacerbated by tramadol.

PMID- 14959958
TI  - Recent advances in pre-eclampsia and eclampsia.

PMID- 14959959
TI  - Symmetrical peripheral gangrene.
AB  - Symmetrical peripheral gangrene (SPG), seen in a wide variety of medical
      conditions presents as symmetrical gangrene of two or more extremities without
      large vessel obstruction or vasculitis. Fingers, and toes (rarely nose, ear lobes
      or genitilia) are affected. It may manifest unpredictably in conditions
      associated with sepsis, low output states, vasospastic conditions,
      myeloproliferative disorders or in hyperviscosity syndrome. It carries a high
      mortality rate with a very high frequency of multiple limb amputations in
      survivors. Disseminated intravascular coagulation (DIC) is seen in majority of
      cases of SPG. A more or less stereotyped clinical picture of SPG in spite of ever
      widening aetiological spectrum is suggestive of DIC as the final common pathway
      of its pathogenesis. Early recognition of acrocyanosis, quick reversal of DIC,
      effective management of the underlying condition, haemodynamic stabilization and
      (perhaps) anticoagulation with low dose heparin (300-500 iu/hour) may be helpful
      in arresting the progression of pre-gangrenous changes to frank gangrene.
      Vasopressors such as dopamine should be used judiciously in the presence of DIC.
      Development of acrocyanosis and increase in serum lactate levels may be
      indicative of impending SPG and the imperative need to treat DIC as well as the
      underlying condition.

PMID- 14959960
TI  - The role of the anaesthetist in preventing HIV/AIDS in developing countries.

PMID- 14959961
TI  - Are deaths due to prematurity avoidable in developing countries?
AB  - Our aim was to assess the potential for reducing the perinatal mortality rate
      (PNMR) related to spontaneous preterm delivery. Data from 44 Perinatal Problem
      Identification Program sentinel sites around South Africa were used. In each
      perinatal death the primary cause as well as missed opportunities and substandard
      care were discussed and allocated. 3045 perinatal deaths in 78,343 births of > or
      = 1000 g were analysed. There were 518 perinatal deaths (17%) whose primary
      obstetric cause of death was due to spontaneous preterm labour (PNMR 7.48/1000
      births). The most common avoidable factors were delay in seeking help during
      labour (14.7%), lack of neonatal facilities (10.0%), lack of transport (7.3%) and
      inappropriate response to the presence of premature rupture membranes (4.6%). Few
      perinatal deaths could be ascribed to poor antenatal or intrapartum management of
      spontaneous preterm labour. The vast majority of spontaneous preterm births could
      not be prevented within the health institutions. Prevention of deaths due to
      prematurity outside of metropolitan areas will rely on the neonatal care being
      adapted to reduced resources.

PMID- 14959962
TI  - Comparison of outcomes from a district tuberculosis control programme in the
      Pacific: before and after the implementation of DOTS.
AB  - Outcomes are compared for a district tuberculosis (TB) control programme, before
      and after DOTS (directly observed therapy short-course) and a computerized
      register were introduced. There were significant improvements in case holding
      associated with the interventions. The successful treatment rate was 13.6% [95%
      CI (confidence interval), 4.9-23.0] higher and the default rate 9.6% (95% CI, 3.6
      17.3) lower following the introduction of DOTS and the computerized register.
      There was no difference in cure rates or death rates, the notification of new
      cases, the proportion of pulmonary cases or sputum positives. Additional benefits
      associated with the computerized register were improvements in supervision,
      reporting and statistical analysis. The short-course chemotherapy permitted
      flexibility and was well accepted by both health staff and patients. This study
      demonstrates that computerization of TB registration using appropriate software
      is feasible in district TB programmes in resource poor countries and can
      contribute to improving their performance.

PMID- 14959963
TI  - Prevalence of alcohol, drug use and psychoactive substance consumption in samples
      of French and Congolese high school students.
AB  - The aim of this study was to make a first comparative approach to
      teenagers'consumption of psychoactive substances within samples drawn in France
      and in Brazzaville the Congo. The samples consisted of 1637 French high-school
      students and 155 Congolese students. An anonymous questionnaire with 13 closed
      items was completed. Whilst 82.1% of the male and 74.5% of the female French
      students had already consumed some alcoholic drinks, only 42.4% of the male and
      44.0% of female Congolese students had consumed alcohol. French high school
      students were more affected by tobacco addiction: 22.2% (male) and 22.9% (female)
      of the French students smoked daily; only 3.0% (male) and 1.9% (female) Congolese
      students were smokers. The consumption of psychotropic medicines (sedatives,
      anxiolytics or hypnotics) appeared overall to be less among French high school
      students than the Congolese, particularly in boys (11.9% versus 17.2%). This
      consumption was mainly from medicine taken without medical prescription or
      misused. The use of cannabis appeared overall to be higher among French high
      school students (45.9% of males and 31.6% of females) than the Congolese (12.5%
      of males and 7.4% of females).

PMID- 14959964
TI  - Low back pain in an urban population in Southwest Nigeria.
AB  - This cross-sectional study was designed to determine the prevalence and risk
      factors for low back pain in an urban community. A house-to-house enquiry was
      conducted using a questionnaire administered by trained interviewers. Four
      hundred and seventy-four respondents, 271 men (57%) and 203 women (43%)
      participated in the study. The 12-month prevalence of low back pain was 44%,
      while the point prevalence was 39%. Back pain was more prevalent among men (49%)
      than women (39%). It was also associated with a history of trauma and low
      educational status. The prevalence of back pain was highest among farmers (85%)
      and lowest among housewives (32%). The prevalence of low back pain in this
      community is comparable to levels recorded in industrialized countries. However,
      in this study low back pain did not feature as a main cause of morbidity,
      accounting for a mean of 3 days off work per person per year.

PMID- 14959965
TI  - Clinico-epidemiological features of snakebite: a study from Eastern Nepal.
AB  - We studied 604 suspected snakebite cases seen at the peripheral snakebite
      treatment centre, Damak, Eastern Nepal from January to December 2000 using pre
      designed proforma. Seventy-five per cent of the patients were in the age group 11
      40 years. The common victims were farmers (44.2%) and housewives (31.7%). The
      bite was commonly encountered during farming (29.4%), working in the field
      (16.2%), walking (13.7%) and feeding cattle (9.2%). Sixty-five per cent were
      bitten during outdoor and agriculture related activities. Bite during sleep was
      recorded in 7%: 62% had sustained bite in lower limb. Forty-two per cent of the
      victims arrived at the treatment centre within 2 hours of being bitten. Fourteen
      patients arrived 7 hours after being bitten and six were dead on arrival. A
      common local practice (seen in 56.7%) was to eat chillies to confirm
      envenomation. Application of a tourniquet, often multiple, was the common (90%)
      first aid measure. Neurotoxicity was present in 11% (n=66) of the victims. Five
      had local features of envenomation. No case of coagulopathy was recorded.
      Reaction to anti-snake venom was noticed in 28.16% (n=20). Two patients died
      during treatment. Mortality among patients with features of neurotoxicity was 3%.

PMID- 14959966
TI  - Improvised tracheal tube for intubation through a laryngeal mask airway.

PMID- 14959967
TI  - Digital polypectomy: a simple technique for rectal polyps in children.
AB  - Excision, suture ligation and endoscopic snaring are the recommended methods of
      treatment for a juvenile rectal polyp. A successful experience of a simpler
      technique, digital polypectomy, in 218 cases is reported.

PMID- 14959968
TI  - A local replacement of tulle gras using palm oil-soaked gauze.

PMID- 14959969
TI  - Accuracy of aneroid sphygmomanometer blood pressure recording compared with
      digital and mercury measurements in Brazil.
AB  - Digital, mercury and aneroid blood pressure measurements were carried out in 400
      South American adults. There was slight under-reading of the aneroid instrument
      (hypertension prevalence 30%, compared with 32% for digital and mercury), but its
      robustness and simplicity makes it a suitable alternative to mercury machines in
      tropical field conditions.

PMID- 14959970
TI  - Screening for intestinal helminth infection in a semi-urban cohort of pregnant
      women in Uganda.

PMID- 14959971
TI  - The stool examination reports amoeba cysts: should you treat in the face of over
      diagnosis and lack of specificity of light microscopy?
AB  - Amoebiasis is a common clinical diagnosis in tropical settings and clinicians
      continue to treat asymptomatic carriers diagnosed by light microscopy. A minority
      of carriers, however, are infected with Entamoeba histolytica and the remaining
      with the non-pathogenic Entamoeba dispar. We compared the diagnostic results of
      298 asymptomatic residents of Aracaju, Brazil, obtained by different diagnostic
      methods, and ascertained their clinical symptoms, to highlight the implications
      for practitioners. Fifty-eight (19.4%) specimens were amoebae positive by
      microscopy. Of these, 38 (13%) were E. histolytica/E. dispar enzyme-linked
      immunosorbent assay (ELISA) positive and 4 (1%) E. histolytica ELISA positive.
      The frequent use of anti-amoebic treatment on the basis of non-specific symptoms
      and the findings of light microscopy tests is not justified. Methods for the
      specific diagnosis of E. histolytica infection for developing countries are
      urgently needed.

PMID- 14959972
TI  - Migration in far western Nepal: a time bomb for a future HIV/AIDS epidemic?

PMID- 14959973
TI  - Oral enalapril-hydrochlorothiazide-methyldopa as first line treatment for severe
      hypertension in Nigerians.
AB  - A combination of low-dose oral enalapril, methyldopa and hydrochlorothiazide was
      evaluated in the acute treatment of severe hypertension. Blood pressure moved
      from an average 210/120 mmHg at the onset to an average 135/79 mmHg within 24
      hours, without any significant side effects and at about half the cost of
      commonly used parenteral hydralazine.

PMID- 14959974
TI  - Acute scrotum in Nigeria: an 18-year review.
AB  - One hundred and seventy-eight patients presenting with an acute scrotum during a
      period of 18 years (1978-1997) were reviewed retrospectively. Fifty per cent had
      testicular torsion, with a mean age of 23 years (range 3 weeks-55 years). Torsion
      was significantly more common in the cold harmattan season (October-early March).
      The salvage rate of torted testes was 52%. Inguinoscrotal hernia was the cause of
      testicular infarction in 10% and is an important contributor to male infertility.
      Twelve per cent of cases of suspected torsion were found to have epididymo
      orchitis, at exploration. Twenty-three (13%) patients presented with scrotal
      gangrene (Fournier's gangrene) which did not result in testicular loss. There was
      significant morbidity following intervention by non-doctors, and misdiagnosis
      from unsuspecting physicians. The acute scrotum affecting young patients is a
      significant cause of male infertility and morbidity in Zaria. Early recognition,
      prompt treatment and re-education of those who may provide the first line care
      for such patients will reduce the morbidity and pathologic consequences following
      neglect.

PMID- 14959975
TI  - Tuberculous appendicitis in India.
AB  - Tuberculous appendicitis (TBA) is a rare condition. The present study has been
      conducted to study its prevalence and presentation. This retrospective study was
      performed in the Department of Surgery, NSCB Government Medical College,
      Jabalpur, MP, India, in 870 consecutive appendectomies performed between January
      1991 and December 2000. Of 870 consecutive appendicular specimens, 10 cases of
      primary (1.1%) and 16 of secondary TBA (1.8%) were encountered. Results of all
      pre-operative investigations were non-specific and the diagnosis was made only
      after histopathology. The prevalence of TBA in this study was 2.9%. Although it
      is a rare condition, its possibility should be kept in mind by clinicians as well
      as pathologists. All surgically removed appendix specimens should be
      histopathologically examined, whether or not the specimens are macroscopically
      normal. Given antitubercular treatment in addition to appendectomy, patients
      recover without complications.

PMID- 14959976
TI  - Iodized salt utilization pattern and availability status in the selected
      districts of Tamilnadu.
AB  - Less than 10% salt contains the recommended levels of iodine. The lifting of the
      ban on the sale of non-iodized salt could put pregnant women and children in
      developing countries at risk.

PMID- 14959977
TI  - Is Crohn's disease in Pakistan less severe than in the West?

PMID- 14959978
TI  - Paediatric day-case surgery at NAUTH, Nnewi, Nigeria.
AB  - Day-care surgery is strongly advocated in well-selected paediatric cases when the
      complications are within acceptable limits because it is very cost effective.

PMID- 14959979
TI  - Transverse lie in labour: alternative options.

PMID- 14959980
TI  - Smoking habits amongst house physicians working at Jinnah Postgraduate Medical
      Center, Karachi, Pakistan.
AB  - The objective of this study was to estimate the prevalence of smoking among house
      physicians working at Jinnah Postgraduate Medical Center, Karachi, Pakistan.
      Sixty-four (32%) of the 200 house physicians were smokers; 50% (36) had started
      smoking in their twenties and 44% (28) in their teens. Seventy-five per cent (48)
      of the smokers were influenced by friends, 20% (13) by cigarette commercials and
      the remainder by their parents. Ninety-five per cent (61) smoked during duty
      hours. The frequency of smoking among young doctors was higher than the overall
      prevalence of smoking in Pakistan.

PMID- 14959981
TI  - Live ascariasis of gall bladder and bile duct: clinical and radiological
      features.

PMID- 14959982
TI  - Ruptured tubal gestation: an unusual presentation of Schistosoma haematobium
      infection of the fallopian tube.
AB  - An unusual mode of presentation of schistosomiasis in the form of a ruptured
      tubal pregnancy in a previously asymptomatic 23-year-old woman is described.
      Histological examination of the salpingectomy specimens demonstrated Schistosoma
      haematobium ova.

PMID- 14959983
TI  - Caecal volvulus in eastern Nigeria.

PMID- 14959984
TI  - Tuberculosis of the thyroid.

PMID- 14959985
TI  - Unsuspected infective cholestatic jaundice after bilateral tubal ligation.

PMID- 14959986
TI  - Spontaneous rupture of spleen in term pregnancy.

PMID- 14959987
TI  - Induction of labour for intrauterine deaths using extra amniotic saline infusion.

PMID- 14959988
TI  - Childhood brucellosis in eastern Turkey.

PMID- 14959989
TI  - Bacteriological profile of post-neurosurgical meningitis in Indian children.

PMID- 14959990
TI  - Retrospective evaluation of malaria patients in Turkey.

PMID- 14959991
TI  - Postoperative orthopaedic infections in Nepal.

PMID- 14959992
TI  - Incisional herniae.

PMID- 14959993
TI  - Legalizing abortion does not reduce serious medical consequences.

PMID- 14959994
TI  - Nursing research linking genetics and health.

PMID- 14959995
TI  - Patient safety.

PMID- 14959996
TI  - Leadership succession planning: would nursing benefit?

PMID- 14959997
TI  - Gender and ethnic differences in a case-control study of dyslipidemia: using the
      apolipoprotein A-V gene as an exemplar in cardiovascular genetics.
AB  - Common, complex genetic disorders such as coronary heart disease (CHD) frequently
      show large population differences, contributing to health disparities. It is also
      well known that CHD risk factor profiles and the frequency of coronary events
      differ by gender. Study of premature CHD has revealed that apolipoproteins are
      important discriminating factors for distinguishing individuals with CHD. Recent
      findings indicated that apolipoprotein A-V (APOA-V) gene promoter polymorphisms
      are an important determinant of plasma triglycerides (TG) and lipoprotein
      cholesterol, and a risk factor for CHD. Variations in APOA-V may have varying
      impacts in different ethnic groups. The purpose of this interdisciplinary genetic
      research project was to determine (1) the association of the APOA-V polymorphisms
      with lipoprotein profiles, and (2) the gender and ethnic differences in the T
      1131C promoter polymorphism of the APOA-V gene in individuals with dyslipidemia
      versus controls. Results indicate that the minor -1131C allele (CC homozygotes +
      CT heterozygotes) was associated with elevated plasma TG (p = 0.007), very low
      density lipoprotein (VLDL)-TG (p = 0.019), LDL-TG (p = 0.004), high-density
      lipoprotein (HDL)-TG (p < 0.001), and VLDL-cholesterol (p = 0.008). We found a
      striking elevation in the frequency of the minor C allele in Asians (p < 0.001)
      compared to Europeans. We also found a significant difference in genotype
      frequency between men and women in Asians (p = 0.031) and Europeans (p < 0.01).
      Remarkably, Asian women with the C allele have a 36% increase in TG compared to
      Asian women homozygous for the T allele. In summary, we found significant ethnic
      specific and gender-based differences in the frequency of the minor allele of the
      -1131 APOA-V gene promoter polymorphism. Identification of genetic variations
      among ethnic groups and between genders may have significant potential for a
      better understanding of the development of cardiovascular disease.

PMID- 14959998
TI  - A LRPAP1 intronic insertion/deletion polymorphism and phenotypic variability in
      Alzheimer disease.
AB  - Alzheimer disease (AD) is a neurodegenerative disorder, characterized by
      dementia. AD exhibits variability in age at onset, rate of progression, and
      specific cognitive, functional, and behavioral features. Genetic variants are
      potential modulators of phenotypic variability. The purpose of this study was to
      explore the relationship between a polymorphism in the Low Density Lipoprotein
      Receptor Related Protein-Associated Protein (LRPAP1) gene (4p16.3) and repeated
      measures of cognition, function, and behavior in persons with AD, using outcome
      data collected in two caregiver intervention studies. Thirty-seven subjects
      diagnosed with probable or possible AD were recruited. All subjects were
      genotyped for a 37 basepair insertion/deletion polymorphism in intron 5 of the
      LRPAP1 gene. No differences in allele or genotype frequencies by gender or by age
      at onset were identified. No statistically significant genotype effects upon
      cognition or behavior were identified. However, trends were noted in measures of
      language, with the LRPAP1 insertion-positive subjects exhibiting poorer language
      scores (average score difference = 28%, p = .158). LRPAP1 insertion-positive
      subjects also were more functionally impaired than subjects without the LRPAP1
      insertion allele (F1,7 = 7.36, p = .030). These results suggest genetic
      variations at the LRPAP1 locus may modulate AD phenotype beyond risk for disease.

PMID- 14959999
TI  - The effect of a genetic variant for obesity and Type 2 Diabetes on the
      therapeutic potential of exercise and calorie restrictive diets in Zucker rats.
AB  - Obesity and Type 2 Diabetes are modern pandemics caused by unique genetic
      environmental interactions and distinguished by almost universal treatment
      failures. Relative influences of genome and lifestyle changes on an adult onset
      Obesity-Type 2 diabetes phenotype were explored. Zucker rats, a recessive model
      of genetic obesity-Type 2 Diabetes (117 fa/fa and 98 Fa/fa) were used. Dietary
      induced obesity (DIO) was imposed via a high fat diet on one-half; and one-half
      were forced to swim daily (EX). After 6 weeks, 78 animals were placed on a
      calorie (Kcal) restrictive diet for 6 more weeks. Genotype accounted for > 20%
      additional insulin resistance and obesity and modulated the effects of DIO and EX
      in adult animals exhibiting obesity-Type 2 diabetes. Only DIO gains were
      responsive to Kcal restriction. EX effects on insulin resistance were mediated by
      both Kcal restriction and genotype. Kcal restriction directly reduced
      hyperglycemia. Genetic variation was the major determinant of obesity and Type 2
      Diabetes in Zucker rats. Genetically induced obesity and insulin sensitivity were
      resistant to EX and Kcal restriction; DIO and hyperglycemia were responsive to
      both. Successful treatment of Type 2 Diabetes requires understanding of how
      genotype may continue to modify adult responses to lifestyle change.

PMID- 14960000
TI  - Discovering and addressing the client's lay construct of genetic disease: an
      important aspect of genetic healthcare?
AB  - Genetic health care includes provision of information about (a) the cause of the
      condition, (b) recurrence risks, and (c) options for avoiding or treating the
      disease. This specialized aspect of health care may be offered by appropriately
      trained nurses, doctors or genetic counselors, but for brevity in this article
      the term "genetic counselor" will be used to describe any health professional
      providing such care. The accepted definitions of genetic counseling emphasize the
      transfer of information from the counselor to the client, to facilitate the
      client in making informed decisions (Ad Hoc Committee on Genetic Counseling,
      American Society of Human Genetics, 1975; Harper, 1998). However, it is important
      to recognize that both clients and counselors bring to the process of genetic
      counseling their own knowledge, values, and beliefs (Hallowell & Richards, 1997).
      The information provided during the genetic counseling process may not be novel
      to the client, and will be received against a background of the client's previous
      knowledge about the condition.

PMID- 14960001
TI  - Genetic content in Japanese language nursing textbooks.
AB  - The purpose of this study was to assess the amount of genetic content included in
      Japanese language nursing textbooks. A total of 222 Japanese nursing textbooks
      for registered nurses, public health nurses, and nurse midwives published by five
      publishers in 2001 were evaluated for genetic content. The textbooks were
      reviewed for content in fundamental knowledge of genetics, genetic diseases,
      genetic counseling, and nursing care for patients with genetic problems. Results
      from the review indicated that although information about genetics was found in
      more than half of the textbooks, descriptions of the roles of nurses in genetic
      counseling and nursing interventions related mostly to single gene disorders.
      These findings suggest that not all Japanese nursing textbooks contain genetic
      content and that they do not include the latest knowledge concerning common
      diseases and genetic nursing interventions. Although the study did not review
      other educational methods, based on these findings, nursing educators in Japan
      should introduce textbooks with genetic information that will prepare registered
      nurses, public health nurses, and nurse midwives to remain current in genetic
      concepts and to apply these concepts to their nursing roles through genetic
      counseling and patient care.

PMID- 14960002
TI  - Genetics and beyond--its interface with nursing research.

PMID- 14960003
TI  - Caries-preventive effect of fissure sealants: a systematic review.
AB  - The objectives of this study were to evaluate systematically the evidence of the
      caries-preventive effect of fissure sealing of occlusal tooth surfaces and to
      examine factors potentially modifying the effect. The search strategies included
      electronic databases, reference lists of articles, and selected textbooks.
      Inclusion criteria were randomized or quasi-randomized clinical trials or
      controlled clinical trials comparing fissure sealing with no treatment or another
      preventive treatment in children up to 14 years of age at the start; the outcome
      measure was caries increment; the diagnostic criteria had been described; and the
      follow-up time was at least 2 years. Inclusion decisions were taken and grading
      of the studies was done independently by two of the authors. The main measure of
      effect was relative risk reduction. Thirteen studies using resin-based or glass
      ionomer sealant materials were included in the final analysis. The results showed
      that most studies were performed during the 1970s and a single application had
      been utilized. The relative caries risk reduction pooled estimate of resin-based
      sealants on permanent 1st molars was 33% (relative risk = 0.67; CI = 0.55-0.83).
      The effect depended on retention of the sealant. In conclusion, the review
      suggests limited evidence that fissure sealing of 1st permanent molars with resin
      based materials has a caries-preventive effect. The evidence is incomplete for
      permanent 2nd molars, premolars and primary molars and for glass ionomer cements.
      Overall, there remains a need for further trials of high quality, particularly in
      child populations with a low and a high caries risk, respectively.

PMID- 14960004
TI  - Dietary factors in the prevention of dental caries: a systematic review.
AB  - The aim of this study was, systematically, to evaluate the effect of dietary
      changes in the prevention of dental caries. A search and analysis strategy was
      followed, as suggested by the Swedish Council on Technology Assessment in Health
      Care (SBU). The search strategy for articles published in 1966-2003 was performed
      using electronic databases and reference lists of articles and selected
      textbooks. Out of 714 articles originally identified, 18 met the inclusion
      criteria for a randomized or controlled clinical trial--at least 2 years' follow
      up and caries increment as a primary endpoint. This included the total or partial
      substitution of sucrose with sugar substitutes or the addition of protective
      foods to chewing gum. No study was found evaluating the effect of information
      designed to reduce sugar intake/frequency as a single preventive measure. It is
      suggested that the evidence for the use of sorbitol or xylitol in chewing gum, or
      for the use of invert sugar, is inconclusive. No caries-preventive effect was
      found from adding calcium phosphate or dicalcium phosphate dihydrate to chewing
      gums. The review dearly demonstrates the need for well-designed randomized
      clinical studies with adequate control groups and high compliance.

PMID- 14960005
TI  - Economic evaluation of dental caries prevention: a systematic review.
AB  - The aim of the present study was to perform a systematic review of economic
      evaluations of caries prevention. A search in Medline from 1966 until May 2003
      and a manual search in a number of journals identified 154 references, 74 of
      which were included. There were 17 original studies including an economic
      evaluation, and these form the basis of the present article. The rest were
      reviews, model studies and reports concerning economic practice in dentistry. The
      results show that the reviewed original studies on economic evaluation of caries
      prevention do not provide support for the economic value of caries prevention.
      The scarcity of well-conducted studies, as well as contradictory evidence in the
      reviewed articles, makes it difficult to judge the health-economic effect of the
      studied caries-prevention methods.

PMID- 14960006
TI  - Caries-preventive effect of fluoride toothpaste: a systematic review.
AB  - With a questionnaire addressed to general dental practitioners in Sweden, the
      Swedish Council on Technology Assessment in Health Care launched a project group
      in 1999 to systematically review and evaluate the existing literature on various
      caries preventive methods. The aim of this article was to report findings
      concerning the caries preventive effect of fluoride toothpastes in various age
      groups, with special emphasis on fluoride concentration and supervised versus non
      supervised brushing. A systematic search in electronic databases for articles
      published between 1966 and April 2003 was conducted with the inclusion criteria
      of a randomized or controlled clinical trial, at least 2 years follow-up and
      caries increment in the permanent (deltaDMFS/T) or primary (deltadmfs/t)
      dentition as endpoint. Out of 905 articles originally identified, 54 met the
      inclusion criteria. These studies were assessed independently by at least two
      reviewers and scored A-C according to predetermined criteria for methodology and
      performance. The measure of effect was the prevented fraction (PF), expressed as
      percent. The results revealed strong evidence (level 1) (i) for the caries
      preventive effect of daily use of fluoride toothpaste compared to placebo in the
      young permanent dentition (PF 24.9%), (ii) that toothpastes with 1,500 ppm of
      fluoride had a superior preventive effect compared with standard dentifrices with
      1,000 ppm F in the young permanent dentition (PF 9.7%), and (iii) that higher
      caries reductions were recorded in studies with supervised toothbrushing compared
      with non-supervised (PF 23.3%). However, incomplete evidence (level 4) was found
      regarding the effect of fluoride toothpaste in the primary dentition. In
      conclusion, this review reinforced the importance of daily toothbrushing with
      fluoridated toothpastes for preventing dental caries, although long-term studies
      in age groups other than children and adolescents are still lacking.

PMID- 14960007
TI  - Two different degrees of mandibular advancement with a dental appliance in
      treatment of patients with mild to moderate obstructive sleep apnea.
AB  - The objective of this study was to evaluate the effect of 2 different degrees of
      mandibular advancement, 50% vs. 75% of maximum protrusive capacity, on
      somnographic variables after 1 year of dental appliance treatment in patients
      with mild to moderate obstructive sleep apnea (OSA). A further purpose was to
      compare the number of adverse events on the stomatognathic system. In a
      prospective study, 74 male patients were randomly allocated to receive a dental
      appliance with either 50% (38 patients) or 75% mandibular advancement (36
      patients). After 1 year of treatment, 55 patients completed the follow-up.
      Somnography was performed to measure treatment effects before and 12 months post
      treatment. The apnea, apnea/hypopnea, and oxygen desaturation indices decreased
      significantly in both groups after 1 year (P < 0.001); however, there were no
      differences between the groups. Normalization (apnea index < 5 and apnea/hypopnea
      index < 10) was observed in 79% in group 50 and in 73% in group 75. Few patients
      (< 5%) reported symptoms from the stomatognathic system except for headache (>
      once a week), which was reported in one-third of the patients. Headache was
      significantly more infrequent after 1 year of treatment in both groups (P <
      0.001). No serious complications were observed except for 2 patients who reported
      a painful condition from the temporomandibular joint in either group. In
      conclusion, mandibular advancement with a dental appliance effectively reduces
      the sleep-breathing disorder measured as frequency of apneas, and a pronounced
      mandibular advancement did not show a greater improvement of the medical problem
      compared to less advancement for patients with mild to moderate OSA. On the basis
      of few adverse events in the stomatognathic system or other complications we can
      recommend dental appliance treatment and, for patients with mild to moderate
      obstructive sleep apnea, not starting treatment by more than 50% mandibular
      advancement.

PMID- 14960008
TI  - Craniofacial cephalometric morphology in six-year-old girls with submucous cleft
      palate and isolated cleft palate.
AB  - Ninety-three girls with cleft palate (53 submucous cleft palate (SMCP) and 40
      isolated cleft palate (ICP)), mean age 6.2 years (range 5.5-7.5), were compared
      retrospectively from lateral cephalograms. Forty-three patients with SMCP had had
      surgical treatment at the mean age of 3.4 years (range 0.9-6.8), 10 of the SMCP
      patients were unoperated. Twenty-six patients with ICP had clefts of the hard and
      soft palate, and 14 had clefts of the soft palate only. Palatal closure of ICP
      had been done at the mean age of 1.5 years (range 1.0-2.1). The skeletal
      craniofacial morphology was similar in SMCP and ICP. The maxilla and mandible
      were well related to each other but slightly retrusive in relation to the cranial
      base. The slight skeletal retrusion was significantly more masked by soft tissue
      in patients with SMCP. The patients with SMCP showed higher values for soft
      tissue maxillary and mandibular prominence.

PMID- 14960009
TI  - Use of xylitol chewing gum in daycare centers: a follow-up study in Savonlinna,
      Finland.
AB  - The use of toothbrushes in daycare centers has been questioned because of the
      possibility of infections spreading through unsupervised brushing. Several field
      studies have demonstrated a caries-preventive effect of xylitol chewing gum--a
      measure that could be a practical way of taking care of oral hygiene during
      daycare hours without brushing. A community trial was conducted in Savonlinna,
      Finland to test the caries-preventive effect of xylitol chewing gum at these
      centers. A total of 921 children were recruited. The daycare centers were
      randomly distributed to xylitol chewing gum or brushing groups. An additional 270
      children who had not been in daycare centers were later organized into an
      external reference group in order to check whether the children in the daycare
      centers were representative of all children in Savonlinna. The results revealed a
      statistically significant but clinically small difference between the xylitol and
      brushing groups in favor of the xylitol group. Many families used the daycare
      services irregularly. Changes in workplace, periods of unemployment, the birth of
      other children in the family, etc., affect the likelihood of families keeping
      their children in a daycare center for many years. Despite the fact that
      conditions were not optimal, oral health status in the xylitol group was a little
      bit better than in the control group. The use of xylitol can therefore be
      recommended, especially if the personnel do not have the possibility to supervise
      the brushing.

PMID- 14960010
TI  - The influence of strain and housing on two types of spike-wave discharges in
      rats.
AB  - WAG/Rij rats, a genetic model of absence epilepsy, show two types of spike-wave
      discharges (Type 1 and Type 2) in their EEG activity. The large interindividual
      variation in the expression of the phenotypes (number and mean duration of spike
      wave discharges) suggests that as well as genetic, environmental factors also
      play a role. The aim of our study was to establish effects of strain and housing
      on the incidence and expression of both types of paroxysms. Therefore, WAG/Rij
      and ACI rats were housed from weaning in either an enriched or impoverished
      environment for 60 days. At three months of age the EEG of the rats was recorded
      for four hours to examine the effects of strain and housing on the incidence and
      expression of the two types of paroxysms. Generally, enriched housing led to
      worsening of Type 1 and Type 2 spike-wave discharges (SWD). However, the number
      of affected rats and the expression (number and mean duration) of Type 1 and Type
      2 spike-wave discharges were differently influenced by strain and housing. This
      suggests that Type 1 and Type 2 spike-wave discharges are independent phenomena
      and that number and mean duration of these paroxysms are controlled by different
      mechanisms. Finally, the worsening of absence seizures after enrichment is
      different from what has been found for convulsive seizures.

PMID- 14960011
TI  - Potential pleiotropic effects of Mpdz on vulnerability to seizures.
AB  - We previously mapped quantitative trait loci (QTL) responsible for approximately
      26% of the genetic variance in acute alcohol and barbiturate (i.e.,
      pentobarbital) withdrawal convulsion liability to a < 1 cM (1.8 Mb) interval of
      mouse chromosome 4. 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, making it a
      strong candidate gene for the QTL. Previous work indicates that Mpdz haplotypes
      in standard mouse strains encode distinct protein variants (MPDZ1-3), and that
      MPDZ status is genetically correlated with severity of withdrawal from alcohol
      and pentobarbital. Here, we report that MPDZ status cosegregates with withdrawal
      convulsion severity in lines of mice selectively bred for phenotypic differences
      in severity of acute withdrawal from alcohol [i.e., High Alcohol Withdrawal (HAW)
      and Low Alcohol Withdrawal (LAW) lines] or pentobarbital [High Pentobarbital
      Withdrawal (HPW) and Low Pentobarbital Withdrawal (LPW) lines]. These analyses
      confirm that MPDZ status is associated with severity of alcohol and pentobarbital
      withdrawal convulsions. Using a panel of standard inbred strains of mice, we
      assessed the association between MPDZ status with seizures induced by nine
      chemiconvulsants. Our results show that MPDZ status is genetically correlated
      with seizure sensitivity to pentylenetetrazol, kainate and other
      chemiconvulsants. Our results provide evidence that Mpdz may have pleiotropic
      effects on multiple seizure phenotypes, including seizures associated with
      withdrawal from two classes of central nervous system (CNS) depressants and
      sensitivity to specific chemiconvulsants that affect glutaminergic and GABAergic
      neurotransmission.

PMID- 14960012
TI  - Aggression and arginine vasopressin immunoreactivity regulation by androgen
      receptor and estrogen receptor alpha.
AB  - In the following study, we asked which steroid receptors regulate aggression and
      arginine vasopressin (AVP) immunoreactivity (-ir) in several limbic regions.
      Using spontaneous mutant and knockout mice, we generated a novel cross of mice
      whose offspring lacked estrogen receptor alpha (ER alpha), androgen receptor (AR)
      or both ER alpha and AR. The wild-type (WT) males and females were compared with
      ER alpha knockout (ER alphaKO) male, mutated AR (Tfm) male and ER alphaKO/Tfm
      (double knockout; DKO) male littermates. Animals were gonadectomized and treated
      with 17beta-estradiol (E2) prior to resident-intruder aggression tests. WT and
      Tfm males showed aggression whereas WT females, ER alphaKO and DKO males did not.
      In the lateral septum, WT and Tfm male brains had significantly denser AVP-ir as
      compared with WT females and DKO males. ER alphaKO male brains were intermediate
      in the amount of AVP-ir present. In the medial amygdala, brains from all
      genotypes had equivalent AVP-ir, except DKO males, which had significantly less
      AVP-ir. Overall, the expression of aggressive behavior coincided with AVP-ir in
      WT, Tfm and DKO males. However, in ER alphaKO males and WT females, the amount of
      AVP-ir was not associated with resident-intruder aggression. In sum we have shown
      that E2 acts via ER alpha to regulate aggression in male mice. In contrast both
      ER alpha and AR contribute to AVP-ir in limbic brain regions.

PMID- 14960013
TI  - Behavioral alterations induced by repeated testing in C57BL/6J and 129S2/Sv mice:
      implications for phenotyping screens.
AB  - The C57BL/6JOlaHsd and 129S2/SvHsd mice were tested in a battery designed for
      behavioral phenotyping of genetically modified mice. The study was performed in
      order to reveal the effect of training history on the behavior by comparison with
      the experimentally naive mice in the same tests. Significant strain differences
      were obtained in all experiments. Previous handling and testing reduced
      exploratory activity and emotionality significantly in the mice. The coordination
      ability was better and nociceptive sensitivity was increased in the trained mice.
      The contextual fear was reduced whereas the cued fear was enhanced in the
      experienced mice. The training history did not alter initial learning in the
      water maze. However, after reversal learning the naive mice displayed significant
      preference for both old and new platform locations, whereas the battery animals
      did not exhibit preference to the old location. The experienced mice appeared to
      be less active in the forced swimming test and exhibited decreased conditioned
      taste aversion. The influence of test history was strain-dependent in certain
      cases. Therefore, the experience has substantial consequences on the behavior,
      mainly by reducing exploratory activity, and the previous experience of the
      animals has always to be considered in the analysis of genetically modified mice.

PMID- 14960014
TI  - Cooperation between Drosophila flies in searching behavior.
AB  - In Drosophila melanogaster food search behaviour, groups of flies swarm around
      and aggregate on patches of food. We wondered whether flies explore their
      environment in a cooperative way as interactions between individual flies within
      a population might influence the flies' ability to locate food sources. We have
      shown that the food search behavior in the fruit fly Drosophila is a two-step
      process. Firstly, 'primer' flies search the environment and randomly land on
      different food patches. Secondly, the remaining group of flies move to the most
      favorable food source and aggregate there. We call this a 'search-aggregation'
      cycle. Our data demonstrate that flies do not individually assess all available
      food resources. Rather, social interactions between flies appear to affect their
      choice of a specific food patch. A genetic analysis of this 'search-aggregation'
      behavior shows that flies carrying mutations in specific genes (for example, the
      dunce (dnc) gene which codes for a phosphodiesterase) were defective in this
      search-aggregation behavior when compared to normal flies. Future investigations
      of the neuronal signaling involved in this behavior will help us to understand
      the complexities of this aspect of Drosophila social behaviour.

PMID- 14960015
TI  - Expanded characterization of the social interaction abnormalities in mice lacking
      Dvl1.
AB  - Dvl1 is one of three murine Dishevelled genes widely expressed in embryonic
      development and in the adult central nervous system. Dishevelled proteins are a
      necessary component of the Wnt and planar cell polarity developmental signaling
      pathways. We reported previously that mice deficient in Dvl1 exhibited abnormal
      social interaction and sensorimotor gating. To assess the validity of our earlier
      findings, we replicated the previous behavioral tests and included several new
      assays. The behaviors assessed included: social interaction, sensorimotor
      reflexes, motor activity, nociception, prepulse inhibition of acoustic startle
      (PPI) and learning and memory. Assessments with an explicit social component
      included: social dominance test, whisker trimming, nest building, home-cage
      huddling and ultrasonic vocalization rate analysis in pups. In addition, separate
      cohorts of wildtype and Dvl1-null mice were assessed for social recognition of a
      conspecific. Replicating the original report, Dvl1-null mice were impaired in
      several tasks containing an explicit social component. However, no impairment was
      observed in the social memory task. A previously observed deficit in PPI did not
      replicate in two institutions. In conclusion, we provide evidence that the social
      interaction phenotype of Dvl1-deficient mice has a strong genetic influence, but
      the sensorimotor gating deficit was subject to environmental influences. The
      specificity of observed social interaction deficits also suggests that lack of
      Dvl1 is associated with deficits in the recognition of social hierarchy and
      dominance.

PMID- 14960016
TI  - Neuropsychological and psychosocial correlates of endocrine and metabolic
      disorders--a review.
AB  - With advances in medical knowledge, many paediatric metabolic and endocrine
      disorders can now be treated effectively. The focus of clinical management has
      shifted from survival to quality of outcome for survivors. This paper refers to
      three conditions, congenital hypothyroidism, phenylketonuria and type 1 diabetes
      mellitus, to illustrate the effects of metabolic disturbances on the developing
      brain. Neuropsychological and psychosocial correlates of these disorders are
      reviewed. Current knowledge about illness-related predictors of outcome is also
      discussed.

PMID- 14960017
TI  - Basal and stimulated levels of growth hormone, insulin-like growth factor-I (IGF
      I), IGF-I binding and IGF-binding proteins in beta-thalassemia major.
AB  - A significant percentage of children with beta-thalassemia major shows
      retardation in longitudinal growth as they progress towards puberty due to
      skeletal dysplasia, endocrine gland hypofunction or trace element deficiencies.
      The aim of this study was to evaluate GH/IGF-I secretion and action in
      prepubertal patients with beta-thalas-semia major. Eight prepubertal patients
      with short stature (group A) and seven prepubertal patients with normal stature
      (group B) were studied. Basal and stimulated (after administration of the
      hexapeptide Hexarelin) GH levels were measured with IRMA (Nichols); IGF-I and
      IGFBP-3 levels were measured with RIA (Nichols). IGF-I binding proteins (IGFBPs)
      were analyzed qualitatively with Western ligand blot. IGF-I binding to B
      lymphocytes of the patients was also measured with competitive binding studies
      using human recombinant IGF-I and 125I-IGF-I (Amersham). Basal GH levels did not
      differ statistically between the groups. Peak GH levels after Hexarelin
      stimulation test were higher in group A (A: 27.9 +/- 15.6 ng/ml vs B: 9.1 +/- 4.7
      ng/ml) (Wilcoxon test, p < 0.05). IGF-I levels in the two groups were low-normal
      and comparable (A: 168.0 +/- 81.6 ng/ml vs B: 126.6 +/- 25.5 ng/ml). IGFBP-3
      levels were low in both groups (A: 1.21 +/- 0.27 microg/ml vs B: 1.08 +/- 0.20
      microg/ml). Western ligand blot did not reveal any discernible difference in
      IGFBPs. However, IGF-I binding on B-lymphocytes was at least 20% lower in group A
      compared to group B (t-test, p < 0.01). IGF-I binding inversely correlated with
      peak GH levels (r = -0.54, p < 0.05). Patients in group A were older and
      chronological age correlated with IGF-I levels (r = 0.53, p < 0.05) whereas it
      inversely correlated with IGF-I binding (r = -0.63, p < 0.05). Moreover, patients
      in group A had higher ferritin levels. No correlation was found between ferritin
      levels, desferrioxamine dose/compliance or liver enzyme levels and the parameters
      of the GH axis studied. However, desferrioxamine dose x years correlated with
      IGFBP-3 (r = 0.56, p < 0.05) and correlated inversely with IGF-I binding (r = 
      0.74, p < 0.01). In conclusion, we have shown adequate GH secretion, higher
      secretive capacity after the administration of Hexarelin and lower IGF-I binding
      in prepubertal beta-thalassemic patients with short stature. Whatever the cause,
      reduced IGF-I action has to be considered when treating beta-thalassemic patients
      with short stature.

PMID- 14960018
TI  - Electrophysiological tests of the hearing organ in Hashimoto's disease.
AB  - Thyroid gland diseases resulting from an autoimmunological process may influence
      the hearing organ. The aim of this study was to assess peripheral and central
      parts of the hearing organ in children with Hashimoto's thyroiditis. Thirty
      children (mean age 14.9 years) with Hashimoto's thyroiditis were examined.
      Patients were euthyroid, and presented high blood concentration of
      antithyroperoxidase (ATPO) antibodies. Pure tone audiometry, tympanometry,
      otoacoustic emissions (DPOAEs), and brain auditory evoked potentials (BAEPs) were
      performed. None of the patients had any complaints about hearing acuity; pure
      tone audiometry, tympanometry, and DPOAEs were normal in all patients. There were
      considerable disturbances in auditory nerve and brainstem neural conduction in
      BAEPs. There was positive correlation between the blood concentration of ATPOA
      and the extent of the disturbances in the central part of the hearing organ. One
      should consider the possible presence of subclinical Hashimoto's encephalopathy
      affecting the central part of the auditory organ.

PMID- 14960019
TI  - Endocrine function in thai children infected with human immunodeficiency virus.
AB  - Most children infected by HIV show manifestations which mimic the clinical
      features of endocrine dysfunction, such as failure to thrive and
      hyperpigmentation. Our cross-sectional study was designed to assess the endocrine
      function of Thai children infected with HIV and to determine any relationship
      between disease severity, height and endocrine function. Thirty-six prepubertal
      children infected by HIV, 12 boys and 24 girls, aged 4-12 years (mean +/- SD 7 +/
      2 years), were tested for thyroid function (serum T4, T3, TSH and free T4),
      morning serum cortisol level, serum insulin-like growth factor-I (IGF-I) and IGF
      binding protein-3 (IGFBP-3). Disease severity was assessed using CD4+ T
      lymphocyte percentage. Ten (28%) patients showed abnormal thyroid function. Five
      patients had euthyroid sick syndrome. Thyroid function tests indicated another
      five patients had a condition compatible with compensated hypothyroidism. Most
      patients had normal morning serum cortisol levels. Two-thirds and one-third of
      the patients showed low IGF-I and IGFBP-3 standard deviation scores (SDS),
      respectively. Twenty-six (72%) patients had CD4+ T-lymphocyte <15%, thus were
      classified as severely immune suppressed. A weak linear relationship was
      indicated between disease severity and endocrine function (r = -0.03 to 0.41).
      Statistical significance was found between CD4+ percentage and IGF-I SDS, IGFBP-3
      SDS, serum T3 and free T4 (p-value = 0.03, 0.02, 0.02 and 0.01, respectively.
      Nearly half (44%) the patients were below the third percentile for height of Thai
      children. There was also a weak correlation between height SDS and endocrine
      function (r = -0.03 to 0.41). Statistical significance was observed between
      height SDS and IGF-I SDS, serum T3 and TSH (p-value = 0.02 and 0.01,
      respectively). We conclude that HIV-infected children with demonstrated growth
      failure and greater disease severity tend to have abnormal endocrine function,
      particularly disordered IGF-I levels.

PMID- 14960020
TI  - Homeobox HOXA10 gene analysis in cryptorchidism.
AB  - BACKGROUND: In male mice, targeted disruption of the homeobox gene hoxa10 causes
      cryptorchidism and infertility. Genetic alterations in exon 1 of HOXA10 have been
      found in a high number of boys with cryptorchidism. AIM: To evaluate whether
      mutations of HOXA10 can be a common cause of cryptorchidism. PATIENTS AND
      METHODS: Genomic DNA was extracted from 18 patients with cryptorchidism (age 7-44
      years; unilateral n = 13; no familial cases) and 28 healthy controls (age 9-39
      years). HOXA10 was amplified by PCR and all coding sequences of exon 1 and 2 were
      sequenced. The PCR products were digested by ScrFI restriction enzyme and the
      restriction fragments obtained were analyzed on 2% agarose gel. RESULTS: One
      silent polymorphism, G-->A substitution at position 1203, was detected in 2/18
      patients (11.1%). The same polymorphism was detected in 3/28 controls (10.7%).
      CONCLUSIONS: These data on HOXA10 analysis indicate that alterations of this gene
      may be more rare in males with cryptorchidism than previously suggested. This
      finding agrees with the rare occurrence of INSL3 gene mutations in human
      cryptorchidism, but needs to be confirmed in a larger series of selected
      patients.

PMID- 14960021
TI  - Growth hormone treatment in cartilage-hair hypoplasia: effects on growth and the
      immune system.
AB  - Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive disorder
      characterized by metaphyseal chondrodysplasia with severe growth retardation and
      impaired immunity. We studied the effects of growth hormone treatment on growth
      parameters and the immune system in four children with CHH. The effects of growth
      hormone on growth parameters are the most prominent in patients with the mildest
      growth retardation. However, the effects are temporary and last only for 1 year.
      There is no gain in final height. Serum immunoglobulins did not change during
      growth hormone treatment. We conclude that growth hormone treatment is not
      beneficial in children with CHH.

PMID- 14960022
TI  - Hypothalamic dysfunction after chemotherapy.
AB  - Cranial irradiation with or without chemotherapy can cause hypothalamic-pituitary
      dysfunction. Chemotherapy without cranial irradiation has not been thought to
      cause such deficiency. In order to determine whether chemotherapy without cranial
      irradiation can lead to hormonal deficiency, we reviewed the medical records of
      362 childhood cancer patients who underwent full hypothalamic-pituitary
      evaluation because of altered growth and development after oncological therapy
      (1987-2002). Of these, 31 received chemotherapy but no cranial or total body
      irradiation and had no CNS tumor: 18 had hematological malignancy and 13 had a
      solid tumor of the torso or extremity. Duration of follow-up was 13.0 +/- 4.1
      years (mean +/- SD). Growth hormone deficiency (GHD) was identified in 15 (48%),
      central hypothyroidism (TSH-D) in 16 (52%), and pubertal abnormalities in 10
      (32%). Pubertal abnormalities included precocious puberty in two (6%), gonadal
      failure in five of 27 who were old enough to assess puberty (19%), and
      gonadotropin deficiency in three of 27 (11%). GHD and TSH-D were co-existent in
      eight patients (26%). Overall, 81% (n = 25) had GHD, TSH-D, precocious puberty,
      and/or gonadotropin deficiency. None had ACTH or ADH deficiency or primary
      hypothyroidism. Of note, this was not a study of prevalence, but rather an
      evaluation of clinically referred patients. In conclusion, hypothalamic
      dysfunction may occur in survivors of non-CNS tumors who receive chemotherapy but
      do not receive cranial irradiation. We recommend at least annual observation of
      growth rate and pubertal development of all children treated for pediatric
      malignancies, with evaluation for GHD, TSH-D, pubertal abnormalities, and other
      hypothalamic dysfunction in all poorly-growing cancer survivors, even those not
      treated with cranial irradiation.

PMID- 14960023
TI  - Prevalence of overweight and obesity in male adolescents in Austria between 1985
      and 2000. A population based study.
AB  - OBJECTIVE: To analyse the prevalence of overweight and obesity in young Austrian
      men, to describe a possible time trend during the observation period 1985-2000
      and to define regional differences within the country. DESIGN: Epidemiological
      population based investigation (conscript health investigation) comparing
      aggregated data of four cross-sectional studies. SUBJECTS: Four cohorts of 18
      year-old males (1985: n = 50,475, 1990: n = 47,463, 1995: n 39,275, 2000: n =
      43,503), in total n = 180,716. METHODS: Measurements of height and weight were
      performed during the nationwide conscript health investigation. BMI was
      calculated and overweight was defined as BMI > or = 25.00 kg/m2 and obesity as
      BMI > or = 30.00 kg/m2. Besides height and weight data, information on place of
      residence of the young men was used for the study. Chi-squared and Student's t
      test were calculated to test group differences with respect to their statistical
      significance. RESULTS: The prevalence of overweight increased from 10.9% to 15.5%
      and of obesity from 1.8% to 4.9% during the observation period. A significant
      regional trend was found with the highest prevalence of overweight and obesity in
      the Eastern part of Austria (p < 0.001). BMI was 22.12 +/- 0.34 kg/m2 (mean +/-
      SD) in 1985 and showed a significant increase (p < 0.001) during the study period
      to 22.71 +/- 0.25 kg/m2. CONCLUSION: Overweight and obesity increased remarkably
      in young males in Austria between the years 1985 and 2000. The steepest increase
      was found in the prevalence of obesity and in the Western part of Austria. A
      significant regional difference could be documented during the whole study
      period.

PMID- 14960024
TI  - Effect of iodine supplementation on goiter prevalence among the pediatric
      population in a severely iodine deficient area.
AB  - We evaluated goiter status and urinary iodine excretion (UIC) of 304 school
      children (7-12 years old) 3 years after a law was passed for mandatory production
      of iodinated salt in an area previously characterized by severe iodine deficiency
      in Zonguldak, a mountainous city in the West Black Sea region in Turkey. We
      examined all the children for goiter by palpation, measured sonographic thyroid
      volumes (STV) and UIC. Eighty-two percent of families had been using iodinated
      salt. UIC was above 100 microg/l in 71.2% of the children and median UIC was
      sufficient (143.5 microg/l). The prevalence of goiter was lower at ultrasound
      (14.6%) than by palpation (19.4%). Median STV values were within recommended
      normal limits at all ages. Although Zonguldak had been a highly endemic region,
      it became mildly endemic 3 years after mandatory iodination of salt, with
      decrease of goiter prevalence.

PMID- 14960025
TI  - Priming with testosterone enhances stimulated growth hormone secretion in boys
      with delayed puberty.
AB  - BACKGROUND AND OBJECTIVE: Tests for growth hormone (GH) deficiency are not always
      helpful in the differential diagnosis of physiological delay of growth and
      puberty and GH deficiency. PATIENTS AND METHODS: To enhance diagnostic
      specificity, we used a single dose testosterone priming before repeating the
      arginine stimulation test in 26 boys with short stature and only early signs of
      puberty who failed to show an adequate response of serum GH in the first test.
      RESULTS: 77% (20/26 patients) increased their serum GH peak to more than 10
      ng/ml, whereas six patients were still below this concentration. CONCLUSION: We
      propose that testosterone priming is a useful tool to distinguish between
      physiological delay of growth and puberty and GH deficiency and should be
      included in the diagnostic procedure.

PMID- 14960026
TI  - A novel presentation of familial glucocorticoid deficiency (FGD) and current
      literature review.
AB  - Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder,
      which manifests as isolated glucocorticoid deficiency with normal
      mineralocorticoid function. The disease is secondary to ACTH unresponsiveness,
      with low serum cortisol concentrations in the presence of markedly elevated ACTH
      levels. Approximately 40% of patients with FGD have an identifiable mutation in
      the ACTH receptor gene. The typical presentation of FGD includes recurrent
      hypoglycemia, failure to thrive, and hyperpigmentation prior to 5 years of age.
      Patients with point mutations in the ACTH receptor gene are noted to be of tall
      stature. We report a patient with an atypical initial presentation of this
      condition. Our patient differed from the typical presentation by having late age
      of onset, short stature, and few symptoms of FGD. Sequence analysis of the ACTH
      receptor gene showed compound heterozygosity, with two previously reported
      mutations: S74I and T159K. Her unique presentation further illustrates the
      phenotypic heterogeneity of this disorder in light of reported mutations.

PMID- 14960027
TI  - Addison's crisis in adolescent patients with previously diagnosed diabetes
      mellitus as manifestation of polyglandular autoimmune syndrome type II--report of
      two patients.
AB  - We report on two female adolescents--both diagnosed with type 1 diabetes mellitus
      in early childhood--who presented with signs of severe metabolic decompensation.
      In both cases recompensation was difficult, and during the stay in hospital
      increasing discoloration of palmar creases was observed. ACTH testing
      demonstrated cortisol deficiency in both patients. In addition, autoimmune
      thyroiditis was diagnosed in one patient. As a polyglandular autoimmune syndrome
      was suspected, autoantibody studies were performed and the presence of
      autoantibodies against thyroid and adrenal tissue was established. Polyglandular
      autoimmune syndrome (PGA) type II can lead to subsequent manifestation of
      deficiencies of several endocrine glands. Although PGA type II usually presents
      at a more advanced age, adolescents may also present with the full spectrum of
      the disease. Especially in the presence of Addison's disease, life-threatening
      situations can develop rapidly. Coloration of palmar skin creases of patients
      with known type I diabetes mellitus should serve as a warning sign to be followed
      up with investigation of endocrine functions.

PMID- 14960028
TI  - Autoimmune thyroiditis in association with membranous nephropathy.
AB  - Hashimoto's thyroiditis and membranous nephropathy are believed to be mediated by
      immune mechanisms. A 12 year-old patient is reported who presented with fatigue,
      dislike of cold, pallor and growth retardation. Initial laboratory assessment
      showed moderate proteinuria and impaired renal function (serum creatinine 2.3
      mg/dl), and hypothyroidism due to autoimmune thyroiditis. Light,
      immunofluorescence and electron microscopy of the renal biopsy showed membranous
      nephropathy. The patient recovered from nephropathy after substitution of thyroid
      hormone and therapy with prednisone. Megalin can be envisaged as a potential
      pathogenetic link between the two disease entities. The glycoprotein megalin is
      expressed on thyroid cells in a TSH-dependent manner and may have a crucial role
      in the immunopathogenesis of glomerular injury in membranous nephropathy. For
      similar cases, we want to encourage colleagues to consider this hypothesis and to
      examine blood and renal biopsy specimens for the presence of megalin and
      antibodies against it.

PMID- 14960029
TI  - Seckel-like syndrome: a patient with precocious puberty associated with
      nonclassical congenital adrenal hyperplasia.
AB  - Seckel syndrome is a rare, recessively inherited disorder of severe growth
      retardation with low birth weight and distinct craniofacial, orodental and
      skeletal anomalies. In addition to these characteristics, some cardiovascular,
      hematopoietic, endocrine and central nervous system abnormalities have also been
      described. We report a patient with Seckel-like syndrome who has precocious
      puberty associated with non-classical congenital adrenal hyperplasia (NCCAH). She
      was admitted to our clinic three times. She was diagnosed as having Seckel-like
      syndrome and premature thelarche at the age of 8.9 years. At 10.9 years old she
      was admitted to our clinic with pubic hair and cliteromegaly. Hormonal findings
      revealed NCCAH and hydrocortisone therapy was offered but the patient was non
      compliant. At 13.6 years she had acanthosis nigricans as an additional clinical
      finding and her pubertal stage was 4. She had irregular menses. On hormonal
      evaluation she had euglycemic hyperinsulinism accompanying mild
      hypertriglyceridemia and functional ovarian hyperandrogenism. Premature pubarche,
      hyper-insulinism, dyslipidemia, and hyperandrogenism, and some combinations of
      these, can be associated with reduced fetal growth. This is the first report of
      hyperinsulinism, and probably NCCAH, in association with Seckel syndrome.

PMID- 14960030
TI  - Viral susceptibility of newly established cell lines from the Hawaiian monk seal
      Monachus schauinslandi.
AB  - Ten of 11 cell lines, recently established from the snout (MS-SN), periorbital
      soft tissue (MS-EY), liver (MS-LV), kidney (MS-KD), lung (MS-LG), spleen (MS-SP),
      heart (MS-HT), thyroid (MS-TY), brain (MS-BR) and urinary bladder (MS-UB) of a
      juvenile Hawaiian monk seal Monachus schauinslandi, were evaluated in vitro for
      their susceptibility to 5 mammalian viruses: herpes simplex virus type 1 (HSV-1),
      vesicular stomatitis virus (VSV), reovirus type 3 (Reo-3), poliovirus type 1
      (Polio-1) and vaccinia virus (Vac); 5 fish viruses: channel catfish herpesvirus
      (CCV), infectious hematopoietic necrosis virus (IHNV), infectious pancreatic
      necrosis virus (IPNV), fish rhabdovirus carpio (RC) and viral hemorrhagic
      septicemia virus (VHSV); and 2 marine mammal morbilliviruses: phocine distemper
      virus (PDV) and dolphin distemper virus (DMV). Four well-established continuous
      cell-lines of nonhuman primate (Vero) and fish (EPC, CHSE-214 and BB) origin
      served as controls to standardize the virus infectivity assays. Virus yields were
      quantified as 50% tissue culture infectious dose (TCID50) ml(-1) on Day 7 post
      inoculation. Results of the viral challenge assays revealed that the monk seal
      cell lines shared a similar pattern of susceptibility to the mammalian viruses.
      Despite their different tissue origins, all monk seal cells were sensitive to HSV
      1, Vac, VSV and Reo-3, but were refractory to Polio-1. A characteristic viral
      induced cytopathic effect was noted with VSV and Reo-3, and distinct plaques were
      observed for HSV-1 and Vac. Monk seal cell lines were also susceptible to PDV and
      DMV, 2 morbilliviruses isolated from seals and dolphins, respectively. By
      contrast, these cell lines were generally resistant to VHSV, IHNV and IPNV, with
      varying susceptibility to RC and CCV. The wide range of viral susceptibility of
      these monk seal cell lines suggests their potential value in studying viruses of
      monk seals and other marine mammals.

PMID- 14960031
TI  - Detection and differentiation of yellow head complex viruses using monoclonal
      antibodies.
AB  - Three monoclonal antibodies (MAbs) raised against pathogenic yellow head virus
      (YHV) from Thailand were tested against tissues of shrimp from Thailand,
      Australia, Ecuador and India that were purported to be infected with yellow head
      complex viruses. MAbs V-3-2B and Y-18 were specific to gp116 and gp64 envelope
      proteins, respectively, while Y-19 was specific to a 20 kDa putative
      nucleoprotein p20. As a preliminary step, the site of reactivity of the 3 MAbs in
      YHV was determined by immuno-electron microscopy using ultra-thin sections of YHV
      infected shrimp tissue and negatively stained, semi-purified YHV particles. As
      expected, MAb Y-19 reacted with viral nucleocapsids in ultra-thin sections but
      not with negatively stained, whole virions; MAb V-3-2B did react with negatively
      stained, whole virions, but not with virions or nucleocapsids in ultra-thin
      sections. Unexpectedly, MAb Y-18 did not react with whole or sectioned virions.
      By immunohistochemistry, MAbs Y-19 and Y-18 reacted with Penaeus monodon tissues
      infected with either YHV or with gill-associated virus (GAV) from Australia,
      while MAb V-3-2B reacted with YHV only. In addition, all the YHV and GAV tissue
      samples gave positive in situ hybridization reactions with a cDNA probe specific
      to the ORF1b gene of YHV. They also gave expected differential RT-PCR results for
      YHV and GAV. By contrast, 2 natural Thai shrimp specimens with no gross signs of
      disease gave similar immunohistochemical reactions and RT-PCR reactions to GAV.
      However, sequencing of their RT-PCR products showed that they shared 92.7%
      identity with GAV, but only 79.0% identity with YHV. Although specimens from
      Ecuador and India displayed histopathology suggestive of YHV infection, they gave
      negative immunohistochemical reactions with all 3 Mabs, and negative in situ
      hybridization results. Additional work is required to determine whether a virus
      from the yellow head complex was responsible for their observed histopathology.
      These data show that the 3 YHV MAbs could be used in diagnostic situations to
      differentiate some viruses in the yellow head virus complex.

PMID- 14960032
TI  - Emerging vesiculo-type virus infections of freshwater fishes in Europe.
AB  - Rhabdoviruses were isolated from perch Perca fluviatilis and largemouth bass
      Micropterus salmoides exhibiting clinical signs of disease. Preliminary studies
      indicated that these viruses could be neutralised by antisera to perch
      rhabdovirus (Dorson et al. 1984) and may be similar to those previously isolated
      from grayling Thymallus thymallus and pike-perch Stizostedion stizostedion. The
      relationship between these viruses and the previously characterised fish
      rhabdoviruses, pike fry rhabdovirus (PFRV), spring viraemia of carp virus (SVCV)
      and lake trout rhabdovirus, was investigated. Viruses were propagated in bluegill
      fry (BF-2) cells and were characterised using electron microscopy, serum
      neutralisation tests, immunofluorescence tests, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) and nucleotide sequence analysis.
      The bullet-shaped viral particles appeared to be compact, with spikes visible at
      the surface, a morphology similar to that of the vesiculovirus group of
      rhabdoviruses. Serum neutralisation tests showed that the viruses were
      antigenically closely related to the previously characterised perch rhabdovirus,
      but were not significantly neutralised by antisera to PFRV, SVCV or viral
      haemorrhagic septicaemia virus (VHSV). In immunofluorescence tests with perch
      rhabdovirus antisera, strong specific fluorescence was observed in cell cultures
      infected with the new rhabdovirus isolates, but no fluorescence was observed with
      antisera to PFRV, SVCV or VHSV. SDS-PAGE analysis revealed a polypeptide profile
      typical of vesiculoviruses, but the novel virus isolates had different relative
      mobilities of their P and M proteins compared to PFRV and SVCV. Nucleotide
      sequence analysis was carried out using reverse transcriptase-polymerase chain
      reaction (RT-PCR) and DNA sequencing of a 439 base-pair region of the viral L
      gene. The novel rhabdovirus isolates had <76% nucleotide sequence identity to
      PFRV, SVCV and lake trout rhabdovirus and >95% identity to perch rhabdovirus.
      Phylogenetic analysis using both maximum parsimony and neighbour-joining methods
      assigned the perch rhaboviruses to a separate group to that of PFRV, SVCV and
      lake trout rhabdovirus. These data are the initial characterisation of a group of
      emerging fish vesiculo-type viruses that are biochemically and genetically
      distinct from the PFRV, SVCV and lake trout rhabdoviruses.

PMID- 14960033
TI  - Horizontal transmission of epizootic ulcerative syndrome (EUS)-associated virus
      in the snakehead Ophicephalus striatus under simulated natural conditions.
AB  - Natural transmission of the epizootic ulcerative syndrome (EUS) was conducted on
      naive snakeheads Ophicephalus striatus (also known as Channa striata) kept (A) in
      aquifer water, (B) in lakewater, (C) cohabiting with EUS snakeheads in lakewater,
      and (D) cohabiting with apparently healthy snakeheads in lakewater during the
      1994 to 1995 EUS season. The results showed that EUS-like lesions developed in 6
      to 14 d among naive snakeheads cohabiting with EUS snakeheads and with apparently
      healthy snakeheads in lakewater (Treatments C and D). Among naive fish exposed to
      lakewater (Treatment B), similar lesions developed in 16 to 21 d, while naive
      fish in aquifer water (Treatment A) did not develop EUS-like lesions. EUS signs
      began as Grade I (slight) lesions that gradually progressed to Grades III-IV
      (severe) 3 to 5 d from lesion onset, similar to the naturally affected EUS fish.
      The virus was recovered from some but not all naturally EUS-affected snakeheads,
      snakeheads with healing lesions and apparently healthy snakeheads, but not from
      naive snakeheads. The results provide evidence of a waterborne horizontal
      transmission of the EUS-associated virus. This is the first report of a
      successful horizontal transmission of the EUS-associated virus from apparently
      healthy snakeheads to naive fish under natural conditions and of virus recovery
      in tissue culture from naturally exposed experimental fish.

PMID- 14960034
TI  - Infection of bryozoans by Tetracapsuloides bryosalmonae at sites endemic for
      salmonid proliferative kidney disease.
AB  - Laboratory-reared colonies of the bryozoans Fredericella sultana and Plumatella
      fungosa were placed upstream of 2 fish farms endemic for salmonid proliferative
      kidney disease (PKD) to assess rates of infection of bryozoans by
      Tetracapsuloides bryosalmonae, the causative agent of PKD. Colonies were deployed
      in the field for 8 trial periods of 2 wk each throughout the summer of 2001.
      Following each trial, bryozoan colonies were maintained in laboratory culture for
      28 d and were regularly monitored for infection by searching for sac stages of T.
      bryosalmonae. Infections were never identified by observations of sac stages,
      however positive PCR results and sequencing of cultured material confirmed that
      cryptic infections were present in colonies of both species deployed at one site.
      The possibility that PCR results reflected contamination of surfaces of bryozoans
      can be excluded, given the short period of spore viability of T. bryosalmonae.
      Highest rates of infection occurred when 4 of 23 colonies of F. sultana and 1 of
      12 colonies of P. fungosa were infected during the period 10 to 24 July. No
      infections were detected from mid-August to late October at this site. None of
      the colonies at the other site became infected throughout the period of study.
      Our data provide the first estimates of infection rates of bryozoans by T.
      bryosalmonae. Additionally, they provide evidence that a cryptic stage can be
      maintained within bryozoan hosts for a period of 4 to 6 wk.

PMID- 14960035
TI  - Ultrastructural evidence of autoinfection in the gills of Atlantic cod Gadus
      morhua infected with Loma sp. (phylum Microsporidia).
AB  - Infection by a microsporidian of the genus Loma was found in gills of cod Gadus
      morhua. Xenomas contained parasites in multiple stages of development. Some
      spores looked empty and had everted polar tubes, which were either straight or
      coiled. These polar tubes were scattered throughout the xenoma cytoplasm, and
      some of them pierced the plasma membrane. Those outside of the xenoma penetrated
      neighboring cells, including blood cells. These observations suggest that a
      mechanism of autoinfection could occur in blood cells and gill tissue,
      perpetuating the disease in the host.

PMID- 14960036
TI  - Genetic and morphologic differentiation of Bolbophorus confusus and B. levantinus
      (Digenea: Diplostomatidae), based on rDNA SSU polymorphism and SEM.
AB  - Metacercariae of Bolbophorus species are serious pathogens of farmed fish.
      Molecular diagnostic tools, capable of identifying and differentiating these
      parasites, may assist in the development of rationale control strategies. The
      rDNA 18S (small sub-unit: SSU) genes of adult B. confusus and B. levantinus
      obtained from a pelican, Pelecanus onocrotalus, and a night heron, Nycticorax
      nycticorax, respectively, were amplified, sequenced, and aligned. Based on this
      alignment, we developed a genetic differentiation assay between B. confusus and
      B. levantinus. These 2 species were compared genetically with the North American
      species B. damnificus and Bolbophorus sp. ('Type 2'). The relationship between
      species is outlined and discussed. In addition to the molecular study, specimens
      of B. confusus and B. levantinus were compared morphologically, using scanning
      electron microscopy. Morphologic analysis revealed interspecific differences in
      details of the holdfast organ and the position of the acetabulum.

PMID- 14960037
TI  - Analysis of ribosomal RNA intergenic spacer (IGS) sequences in species and
      populations of Gyrodactylus (Platyhelminthes: Monogenea) from salmonid fish in
      Northern Europe.
AB  - The intergenic spacer (IGS) region of ribosomal RNA genes was amplified and
      sequenced from a variety of Gyrodactylus specimens collected from wild and farmed
      Atlantic salmon Salmo salar, rainbow trout Oncorhynchus mykiss, and grayling
      Thymallus thymallus, from various locations in Northern Europe. Phylogenetic
      analysis of the sequences confirmed the distinction between G. salaris Malmberg,
      1957 and G. thymalli Zitnan, 1960, supporting their validity as separate species.
      G. salaris adapted to rainbow trout are also distinct from the parasites found on
      Atlantic salmon, supporting the existence of a rainbow-trout form that was
      initially identified on the basis of morphological differences. Analysis of the
      IGS did not provide good resolution of different populations of G. salaris sensu
      stricto, but was consistent with epidemiological evidence which indicates that
      introduction of the parasite to Norway was recent and limited. The IGS may be
      helpful in distinguishing forms of G. salaris that are pathogenic to Atlantic
      salmon from those that are not.

PMID- 14960038
TI  - Risk of inter-river transmission of Gyrodactylus salaris by migrating Atlantic
      salmon smolts, estimated by Monte Carlo simulation.
AB  - The possibility of Gyrodactylus salaris infection of wild North Atlantic salmon
      Salmo salar spreading to new rivers poses a major threat in Norway. This
      freshwater parasite can survive for some time in brackish water, and it has been
      suggested that smolts leaving infected rivers could transport vital parasites to
      new rivers. A Monte Carlo simulation model was used to estimate the risk that
      infected smolts would ascend a new river. Data from an infected watercourse in
      Norway, where the salmon population is maintained constant by cultivation, were
      used. The model included information on prevalence of infection, hydrographical
      conditions, survival of G. salaris in brackish water, fish population
      characteristics, and smolt behaviour during seaward migration. The annual risk
      was estimated for 3 neighbouring rivers situated at different distances from the
      index river. For the nearest river, which shares the same brackish water zone
      with the index river, the model estimated an annual risk of 31% that at least 1
      infected smolt would ascend this river. The results of the simulation were highly
      sensitive to the water salinity along the migration route. For the other rivers,
      the annual risk was lower than 0.5%. Risk was positively correlated with the
      number of fish leaving the index river, indicating control of this number as a
      possible tool in risk management.

PMID- 14960039
TI  - Fungicidal effects of chemical disinfectants, UV light, desiccation and heat on
      the amphibian chytrid Batrachochytrium dendrobatidis.
AB  - The efficacy of a number of disinfection treatments was tested on in vitro
      cultures of the fungus Batrachochytrium dendrobatidis, the causative agent of
      chytridiomycosis in amphibians. The aim was to evaluate the fungicidal effects of
      chemical disinfectants, sterilising ultraviolet (UV) light, heat and desiccation,
      using methods that were feasible for either disinfection in the field, in
      amphibian husbandry or in the laboratory. The chemical disinfectants tested were:
      sodium chloride, household bleach (active ingredient: sodium hypochlorite),
      potassium permanganate, formaldehyde solution, Path-X agricultural disinfectant
      (active ingredient: didecyl dimethyl ammonium chloride, DDAC), quaternary
      ammonium compound 128 (DDAC), Dithane, Virkon, ethanol and benzalkonium chloride.
      In 2 series of experiments using separate isolates of B. dendrobatidis, the
      fungicidal effect was evaluated for various time periods and at a range of
      chemical concentrations. The end point measured was death of 100% of zoospores
      and zoosporangia. Nearly all chemical disinfectants resulted in 100%, mortality
      for at least one of the concentrations tested. However, concentration and time of
      exposure was critical for most chemicals. Exposure to 70% ethanol, 1 mg Virkon
      ml(-1) or 1 mg benzalkonium chloride ml(-1) resulted in death of all zoosporangia
      after 20 s. The most effective products for field use were Path-X and the
      quaternary ammonium compound 128, which can be used at dilutions containing low
      levels (e.g. 0.012 or 0.008%, respectively) of the active compound didecyl
      dimethyl ammonium chloride. Bleach, containing the active ingredient sodium
      hypochlorite, was effective at concentrations of 1% sodium hypochlorite and
      above. Cultures did not survive complete drying, which occurred after <3 h at
      room temperature. B. dendrobatidis was sensitive to heating, and within 4 h at 37
      degrees C, 30 min at 47 degrees C and 5 min at 60 degrees C, 100% mortality
      occurred. UV light (at 1000 mW m(-2) with a wavelength of 254 nm) was ineffective
      at killing B. dendrobatidis in culture.

PMID- 14960040
TI  - White spot syndrome virus (WSSV) infectivity for Artemia at different
      developmental stages.
AB  - White spot syndrome virus (WSSV) is a major pathogen of cultivated shrimp, but
      its host range includes a large number of crustaceans. In this investigation,
      Artemia franciscana was tested for susceptibility to WSSV by the oral route. Both
      instars and adults were challenged, and the presence of WSSV was followed through
      to reproductive cysts and offspring using PCR. WSSV caused a much lower
      cumulative mortality in Artemia than in cultivated shrimp by 10 d post-challenge.
      Instars, adults and reproductive cysts were PCR positive. However, the virus was
      undetectable by PCR in nauplii that had hatched from PCR-positive reproductive
      cysts. The data indicate that WSSV or WSSV genomic DNA can be vertically
      transmitted from WSSV-PCR-positive instars to reproductive cysts, but this DNA is
      removed during hatching.

PMID- 14960041
TI  - Effect of methyl parathion on the susceptibility of shrimp Litopenaeus vannamei
      to experimental vibriosis.
AB  - Following increasing calls for environmental safety over the past 2 decades,
      persistent pesticides are being replaced by more rapidly degradable products.
      However, even these pesticides can affect non-target species, and may be
      associated with slow growth and increased susceptibility to viral and bacterial
      infections. In this study, juvenile white shrimp Litopenaeus vannamei (also named
      Penaeus vannamei) were challenged by intramuscular injection with Vibrio
      parahaemolyticus after 4 d prior exposure to methyl parathion in feed pellets at
      0.080 microg g(-1). The bacterial injection control group consisted of shrimp fed
      pellets containing the methyl parathion-carrier solvent acetonitrile. Three
      additional control groups comprised 2 sterile saline-injection groups fed pellets
      containing methyl parathion or acetonitrile prior to injection, and 1 uninjected
      group fed normal pellets. Cumulative mortalities were recorded on the 4th and 8th
      days, and the presence of histological lesions was recorded on the 8th day.
      Cumulative mortalities were significantly higher in the group exposed to methyl
      parathion and bacteria on Day 8. Histological lesions, typical of vibriosis, were
      significantly associated with the injection of V. parahaemolyticus. The study
      provides strong experimental evidence that prior exposure to methyl parathion can
      increase the severity of Vibrio infections.

PMID- 14960042
TI  - Steinhausia mytilovum in cultured mussels Mytilus galloprovincialis in the
      Thermaikos Gulf (northern Aegean Sea, Greece).
AB  - The microsporidian Steinhausia mytilovum was found parasitising female cultured
      mussels Mytilus galloprovincialis L. in the Thermaikos Gulf (northern Aegean
      Sea). The parasites affected the condition index of infected mussels and induced
      a strong hemocyte infiltration inside affected gonadal follicles. The prevalence
      (7.5 to 35.5%) of the parasite was relatively high in a polluted area.

PMID- 14960043
TI  - Hemodynamic and metabolic responses to hypergravity on a human-powered
      centrifuge.
AB  - INTRODUCTION: Microgravity causes the deconditioning of many physiological
      systems, and there is great interest in developing effective countermeasures. We
      recently developed a short-arm human-powered centrifuge, and the primary
      objective of this study was to assess the hemodynamic and metabolic responses to
      exercise under hypergravity conditions. METHODS: Phase I compared the hemodynamic
      and metabolic responses to 1 Gz (upright cycle ergometry) and 2 Gz conditions
      (Space Cycle) at the same work rate. Phase II contrasted the hemodynamic and
      metabolic responses at 2 and 3 Gz and at the same work rate. Phase III examined
      the BP and heart rate (HR) responses during passive and active centrifugation.
      Phase IV examined the relationship between work rate and oxygen uptake. RESULTS:
      In Phase I, the HR and BP responses were very similar between the two Gz
      conditions, with the exception that 2 Gz produced a lower diastolic BP in female
      subjects. In Phase II, both systolic and diastolic BPs were similar under the two
      different Gz conditions. However, there was a significant increase in HR at 3 Gz.
      In Phase III, the slope of the HR/Gz relationship was greater for passive
      conditions, suggesting that venous return is facilitated by the skeletal muscle
      pump. In Phase IV, it was found that there was a highly linear relationship
      between work rate and oxygen uptake. CONCLUSION: The results of this study
      demonstrate that exercise under low hypergravity conditions on the Space Cycle is
      well tolerated from a hemodynamic perspective.

PMID- 14960044
TI  - Oxygen stress effects on proliferation rates and heat shock proteins in
      lymphocytes.
AB  - INTRODUCTION: High-oxygen conditions produce oxidants and cause some
      pathognomonic signs and symptoms in human hosts. However, the biological effects
      at the cellular level are still unclear. To investigate the cellular response
      against oxygen stress, we measured the proliferative activity and heat shock
      protein (HSP) expression of human lymphocytes. METHODS: Hydrogen peroxide (H2O2)
      was used as a source of reactive oxygen species. The time course of the
      proliferative/apoptotic response was evaluated from DNA histogram analysis. HSP
      response was measured by Western blot analysis. RESULTS: Suppression of
      lymphocyte cluster formation by oxygen stress was observed to be dose-dependent.
      Induction of apoptotic cell death and retardation of entering the S-phase were
      also affected according to the extent of oxygen stress. Oxygen stress equivalent
      to 500 micromol x L(-1) H2O2 or more showed a severe impairment of the cell cycle
      and that equivalent to 50-100 micromol x L(-1) H2O2 revealed an intermediate
      effect. Although an increased expression of HSP72/73 was observed in each group 6
      h after oxygen stress, only 100 micromol x L(-1) H2O2-treated cells remained at a
      high expression level after 24 h. CONCLUSION: It is likely that when cells
      encounter oxygen stress, an increased expression of HSP72/73 and subsequent
      repair of damaged proteins cause the retardation of cell cycle progression and
      prevent damaged cells from entering the S phase. But if the damage is too strong,
      the cells may go into apoptotic cell death. From our results of the HSP72/73
      experiment, the threshold that determines the fate of the lymphocytes may be
      around 100 micromol x L(-1) H2O2.

PMID- 14960045
TI  - Responses of plasma proenkephalin peptide F in rats following 14 days of
      spaceflight.
AB  - INTRODUCTION: . Proenkephalin peptide F [107-140] is related to the enhancement
      of immune function, while microgravity has been shown to cause immuno
      suppression. We investigated the physiological response of proenkephalin peptide
      F to microgravity. METHODS: There were 12 Fischer 344 female rats, ovariectomized
      at 10.5 wk of age, used to determine plasma concentrations of peptide F in
      response to a 14-d flight aboard the Columbia Space Shuttle mission STS-62. There
      were 36 other such rats that served as ground-based controls to separate the
      effects of microgravity from those of thermal stress, flight stress, and crowded
      habitats. Control groups of 12 rats each were kept under the following
      conditions: 1) 22 degrees C vivarium, 2) 28 degrees C vivarium, and 3) variable
      (Var) to mimic flight. The flight and control groups were housed in animal
      enclosure modules 21 d prior to flight and for the duration of the study. The
      rats were sacrificed within 4-5 h after landing, at which time blood samples were
      obtained. RESULTS: Body weights were obtained prior to sacrifice; mean values
      were flight, 199 g; 22 degrees C, 193 g; 28 degrees C, 192 g; and Var, 194 g. The
      flight group produced a significantly greater (p < or = 0.05) level of plasma
      peptide F (0.056 pmol x ml(-1)) compared with the controls (0.016, 0.022, and
      0.016 pmol x ml(-1) for 22 degrees C, 28 degrees C, and Var, respectively).
      Flight animals demonstrated higher corticosterone concentrations and reduced T
      and B cell splenocyte counts than controls. CONCLUSIONS: These data indicate that
      the increases in proenkephalin peptide F observed with exposure to microgravity
      may present an adrenal-medullary response to cope with the decreased immune
      function and increased stress experienced during spaceflight and landing.

PMID- 14960046
TI  - Changes in superficial blood distribution in thigh muscle during LBNP assessed by
      NIRS.
AB  - INTRODUCTION: The present study was designed to determine how superficial blood
      distributed in the lower limb muscle during graded lower body negative pressure
      (LBNP). METHODS: Near-infrared spectroscopy (NIRS) was used to evaluate the blood
      volume change in the thigh muscles of seven volunteers during 35 min graded LBNP
      (rest, -10, -20, -30, -40, -50 mm Hg, and recovery). RESULTS: Deoxygenated and
      total hemoglobin (Hb) increased in proportion to the magnitude of LBNP applied to
      the thigh muscles. Oxygenated Hb rose significantly at -10 mm Hg LBNP, although
      the increase leveled off during subsequent increments of LBNP. Systolic pressure
      significantly decreased from 120 mm Hg at rest, to a value of 108 at -50 mm Hg
      LBNP. In contrast, mean and diastolic pressures were well maintained during
      graded LBNP. The increased total and deoxygenated Hb might indicate that blood
      was held in venous space, and the magnitude of rise in blood volume corresponded
      to the change in LBNP. On the other hand, oxygenated Hb change seems to reflect
      mainly blood accumulated in arterial space by interacting between mechanical
      stretch induced by LBNP and vasoconstriction caused by augmented sympathetic
      nerve activity. CONCLUSION: From these results, blood distribution in thigh
      muscles was different and was affected by the strength of LBNP. The data
      assessing oxygenation sites of Hb were found to be useful as indices of
      estimating superficial blood pooling in the muscle during LBNP.

PMID- 14960047
TI  - Neck muscle activity and perceived pain and discomfort due to variations of head
      load and posture.
AB  - BACKGROUND: The increasing use of helmet-mounted displays in aviation raises
      issues of head-supported weight and neck musculoskeletal function, especially
      during acceleration. OBJECTIVES: This study aimed to quantify musculoskeletal
      stress as weight was added to the front of the head in different head positions
      and determine the effectiveness of a counterbalance in reducing stress. METHODS:
      There were 20 subjects who participated. The study required that the subject move
      his head every 10 s for 10 min to one of five positions that were assumed to
      represent those readily adopted in everyday situations: neutral, 30 degrees
      extended, 30 degrees flexed, 35 degrees left rotated, and 35 degrees right
      rotated. Of the subjects, 10 repeated the test while wearing a GSMK6 helmet, and
      when 0.5 kg, 1.0 kg, or 2.0 kg was added to the front of the helmet. The other 10
      subjects repeated the test but with counterbalances. During testing, EMG was
      recorded from the neck extensors and sternocleidomastoid muscle. Pain levels were
      recorded using the Borg-CR10 scale. RESULTS: Changes in head position from
      neutral resulted in significant increases of EMG amplitude (mean +/- SD) in the
      neck extensors of up to 18 +/- 13% (p < 0.05), and due to head load by 46 +/- 33%
      (p < 0.05) with a frontal load of 2 kg. Sternocleidomastoid EMG showed little
      change due to increases in load but increased significantly by up to 265 +/- 227%
      of the neutral position (p < 0.05) when the head was rotated. CONCLUSIONS: The
      use of head-mounted displays presents the risk of detrimental effects to the
      musculoskeletal system. Determining the effect of added weight requires a
      knowledge of working head postures.

PMID- 14960048
TI  - Speech intelligibility with helicopter noise: tests of three helmet-mounted
      communication systems.
AB  - BACKGROUND: Military aviator helmet communications systems are designed to
      enhance speech intelligibility (SI) in background noise and reduce exposure to
      harmful levels of noise. Some aviators, over the course of their aviation career,
      develop noise-induced hearing loss that may affect their ability to perform
      required tasks. New technology can improve SI in noise for aviators with normal
      hearing as well as those with hearing loss. METHODS: SI in noise scores were
      obtained from 40 rotary-wing aviators (20 with normal hearing and 20 with hearing
      loss waivers). There were three communications systems evaluated: a standard SPH
      4B, an SPH-4B aviator helmet modified with communications earplug (CEP), and an
      SPH-4B modified with active noise reduction (ANR). RESULTS: Subjects' SI was
      better in noise with newer technologies than with the standard issue aviator
      helmet. A significant number of aviators on waivers for hearing loss performed
      within the range of their normal hearing counterparts when wearing the newer
      technology. The rank order of perceived speech clarity was 1) CEP, 2) ANR, and 3)
      unmodified SPH-4B. CONCLUSIONS: To insure optimum SI in noise for rotary-wing
      aviators, consideration should be given to retrofitting existing aviator helmets
      with new technology, and incorporating such advances in communication systems of
      the future. Review of standards for determining fitness to fly is needed.

PMID- 14960049
TI  - Atmospheric changes and physiological responses during a 6-day "disabled
      submarine" exercise.
AB  - BACKGROUND: Survival time within a disabled submarine (SUBSUNK) is dependant on
      atmospheric composition and proper design and use of emergency atmospheric
      control systems. The objective of this study was to investigate atmospheric
      changes and physiological responses during a SUBSUNK trial. METHODS: There were
      18 volunteers who were restrained within a 250 m3 front compartment of an Ula
      class submarine submerged in 8 degrees C seawater for 6 d, 18 h. Atmospheric
      control was maintained according to emergency procedures using non-electrically
      powered chemical CO2 absorption, and O2 was replenished using chlorate candles.
      Atmospheric parameters, skin and body temperatures, weight, urine, and drinking
      volume were measured. Subjective responses to cold were measured on a visual
      analog scale (VAS), and symptoms were logged on the environmental symptoms
      questionnaire (ESQ). RESULTS: Atmospheric temperature gradually decreased to a
      minimum of 14.1 degrees C. Toe, heel, and finger temperatures decreased
      significantly. Subjects reported inferior subjective thermal comfort on the VAS
      and increased cold stress on the ESQ. Except for CO2, no inorganic or volatile
      organic compounds exceeded occupational exposure limits. The PO2 and PCO2 ranged
      from 17.4-20.3 and 1.9-2.8 kPa, respectively, during the first 5 d. During the
      last 2 d, PO2 and PCO2 were deliberately maintained at about 15.8 and 3.1 kPa,
      respectively. Mean oxygen consumption and CO2 production were 23.8 and 19.8 L
      standard temperature and pressure (STP) x man(-1) x h(-1), respectively. Soda
      lime and lithium hydroxide CO2 absorption capacities were 126 and 405 L STP x kg(
      1) respectively. CONCLUSIONS: Atmospheric conditions can be controlled acceptably
      for 6 d, 18 h within the front compartment of an Ula-class submarine operating
      according to emergency SUBSUNK procedures.

PMID- 14960050
TI  - Preventing G-induced loss of consciousness: 20 years of operational experience.
AB  - INTRODUCTION: Although anecdotal reports of G-induced loss of consciousness (G
      LOC) in military aviation date back to before 1920, regular reporting did not
      begin until 1982. The effectiveness in the operational setting of G-LOC
      preventive measures, such as positive pressure breathing for G protection (PBG),
      has not been studied. METHODS: We use the term "crash" to represent an event
      where the aircraft was destroyed and "incident" to define those events where the
      crew reported a G-LOC episode and the aircraft was not damaged. Data on G-LOC
      crashes, incidents, and aircraft sorties (number of take-offs) were obtained from
      the USAF Safety Center database for FY 82-01. RESULTS: During FY 82-01, there
      were 29 G-LOC crashes while those aircraft at risk of G-LOC crashes flew a total
      of 13,959,816 sorties. Poisson regression showed a non-significant decrease in
      crashes with an incidence rate ratio (IRR) of 0.096 (CI 0.89-1.03) (4% per yr). G
      LOC crashes decreased from 4.4 per million flight sorties (PMFS) to 1.6 after the
      implementation of anti-G-LOC training programs beginning in 1985. However, G-LOC
      crashes remained unchanged after implementation of PBG in 1995. In contrast,
      incidents showed an IRR of 1.04 (CI 1.02-1.06) for G-LOC incidents, an estimated
      increase of 5% per yr. DISCUSSION: The physical/mechanical limitations of PBG,
      risk homeostasis, and the possibility that G-LOC rates have reached their
      asymptotic minimum are all discussed as possible explanations for the failure of
      PBG to decrease G-LOC crashes.

PMID- 14960051
TI  - Cervical and lumbar spinal changes diagnosed in four-view radiographs of 732
      military pilots.
AB  - BACKGROUND: Pilots who fly jet fighters or helicopters frequently experience
      vertebral problems due to acceleration and vibration, wearing helmets and other
      headgear, and sitting in suboptimal postures. METHODS: We looked for
      spondylarthritic or spondylitic changes in 4-view radiographs (AP, lateral, left
      and right oblique) of the cervical and lumbar vertebrae of 732 pilots and 202 non
      flying controls. The subjects included 91 F-16 jet pilots, 363 other jet pilots,
      119 transport pilots, and 159 helicopter pilots. RESULTS: The prevalence of
      cervical changes in helicopter pilots was 19%, significantly higher than those
      for other pilots (8-13%) or controls (10%). There was no difference among groups
      with respect to prevalence of lumbar changes. Among all pilots, compression
      fractures were more common in the lumbar region than in the cervical region. Age
      was the most important variable related to spondylarthritic or spondylitic
      changes in all subjects, whereas height was an important factor only among jet
      pilots. CONCLUSION: We found an increased prevalence of cervical changes,
      especially osteoarthritis, in helicopter pilots. Increasing age and tall stature
      were associated with an increased prevalence of vertebral spondylarthritic or
      spondylitic changes in jet pilots.

PMID- 14960052
TI  - Cranial MRI as a screening tool: findings in 1,772 military pilot applicants.
AB  - BACKGROUND: Beginning 1 January 2000, during the selection process, the German
      Air Force Institute of Aviation Medicine screens all applicants for flying duty
      using cranial MRI to rule out relevant intracranial abnormalities. Type and
      frequencies of abnormalities and aeromedical consequences are described. METHODS:
      An intracranial MRI is done on every applicant regardless of the findings of the
      physical examination. RESULTS: From 1 January 2001 to 31 December 2002 we
      investigated a total of 1,772 applicants with cranial MRI. All of these had
      normal findings in both the general medical and neurological examinations. We
      found that 81.7% (1,452) were normal, 9% (160) had variations of the norm, 8.4%
      (148) had findings of unknown significance (e.g., arachnoid cysts, white matter
      lesions, etc.), and only 0.7% (12) had definite abnormal findings (arteriovenous
      malformations, cavernomas, tumors). CONCLUSION: Evident pathological cases are
      rare. However, cranial MRI screening adds substantial new information, increasing
      the value of the initial examination and making it possible to extend the
      examination according to the clinical indications. This leads to a highly
      individualized appraisal of the applicant, thus increasing flight safety.

PMID- 14960053
TI  - An electromyographic assessment of the anti-G straining maneuver.
AB  - BACKGROUND: The anti-G straining maneuver (AGSM), used by aircrew to enhance
      their +Gz tolerance and to reduce the potential risk of G-induced loss of
      consciousness, has been recognized as an effective technique. The purpose of this
      study was to establish an objective tool to evaluate the effectiveness of an
      aircrew member's AGSM. METHODS: There were 20 healthy subjects who participated
      in the study, including 8 senior aviation physiological trainers and 12 trainees.
      The former were familiar with the anti-G maneuver and had experienced high +Gz
      exposure, the latter had never been exposed to any high +Gz stress before the
      study. The analytic method of electromyography (EMG) was used to investigate the
      physical characteristics of the L-1 AGSM. RESULTS: Comparison of the EMG data
      from the two groups indicated that the mean duration of a breathing cycle of the
      trainer group was significantly longer than that of the trainee group (p <
      0.001). The buccinator was the muscle that had the most rapid firing rate in both
      groups (p < 0.001). The trainer group had a significantly faster firing rate of
      the buccinator than the trainee group (p = 0.03). In addition, the trainee group
      performed the AGSM with a firing sequence of muscles that was different from that
      of the trainer group. CONCLUSIONS: An automated and quantitative system based on
      EMG can be used during AGSM training to augment or replace the current subjective
      evaluation of the trainee's performance.

PMID- 14960054
TI  - Tracer study of proximity and recirculation effects on exposure risk in an
      airliner cabin.
AB  - There is continuing concern about whether and to what extent airliner cabins
      represent an increased risk of transmission of airborne infectious disease. The
      purpose of this study was to examine through a simple experiment the relative
      importance of close proximity and partial recirculation of cabin air on the
      potential risk of disease transmission. Results are presented from measurements
      of instantaneous point source dispersion in a cabin on a commercial airline
      flight. A small amount of tracer gas was released as a puff in the passenger
      cabin of a wide body jet at cruise altitude. Tracer gas samples were taken
      manually in the period immediately after the release by two technicians sitting 2
      m and 30 m forward of the release point in the cabin. The maximum tracer
      concentration observed at the 2 m sampling point occurred at 5 s after the
      release and was a factor of 500 greater than the maximum observed at the 30 m
      sampling point, which occurred 6.5 min after the release. The integrated tracer
      exposure at the 2 m location was approximately a factor of 30 greater than at the
      30 m location. Assuming risk of transmission is proportional to dose, then the
      results support the hypotheses that infectious diseases are transmitted primarily
      between people sitting in close proximity to each other in an aircraft cabin and
      that partial recirculation of ventilation air in the cabin has a negligible
      impact on occupants' risk of exposure.

PMID- 14960055
TI  - Motion sickness induced by optokinetic drums.
AB  - Motion sickness is not only elicited by certain kinds of self-motion, but also by
      motion of a visual scene. In case of the latter, optokinetic drums are often used
      and a visual-vestibular conflict is assumed to cause the sickness. When the
      rotation axis is Earth vertical however, different studies show different
      results. Here, we propose that visual-vestibular conflicts per se do not cause
      sickness whereas subjective vertical mismatch theory can reconcile the disparate
      findings. The theory attributes the nausea induced by horizontal optokinetic
      stimulation to the subjects self-inducing pseudo-Coriolis by head movement. This
      highlights the shortcomings of an optokinetic apparatus--that is non-rigid or
      inaccurately oriented--and the importance of constraining the subject's behavior.

PMID- 14960056
TI  - Major depressive disorder with psychotic features in an aviator after head
      trauma.
AB  - We present a case in which a Naval aviator suffered an unusual sequence of
      neuropsychiatric symptoms after head trauma. He demonstrated subtle deficits on
      several measures 1 mo after the trauma. Repeat testing at 8 mo showed apparent
      recovery, and the patient was cleared to return to flight status. Unbeknownst to
      medical staff, the patient was still experiencing difficulties. He was found in a
      severely debilitated state and exhibiting psychotic features 12 mo after his
      initial trauma. The patient was hospitalized in a psychiatric ward, and with
      prolonged inpatient and outpatient treatment, he eventually recovered.

PMID- 14960057
TI  - Transcatheter PFO closure in an aircrew member with cryptogenic stroke:
      aeromedical disposition.
AB  - Stroke is an uncommon event among military aircrew, partly because that
      population tends to be younger and healthier than typical stroke victims. Aircrew
      members suffering stroke rarely have identifiable risk factors or etiology that
      can be treated or modified such that return to flying duties is a consideration.
      In this case, an aircrew member was found to have a patent foramen ovale (PFO)
      during his stroke evaluation. Several studies support the association between PFO
      and cryptogenic stroke, but literature clearly defining the need for PFO repair
      in the context of cryptogenic stroke is still incomplete. On clinical
      recommendation from his providers, this aircrew member underwent elective closure
      of his PFO with a transcatheter device. After complete recovery from his stroke
      and an apparently successful PFO closure, he requested return to flying duties.
      History of stroke and PFO closure with transcatheter device were both
      disqualifying conditions according to United States Air Force Instructions. This
      case is presented as an example of an aeromedical decision-making process when
      confronted with an unusual case such as this.

PMID- 14960058
TI  - Human factors of powered flight: the Wright brothers' contributions.
AB  - Orville and Wilbur Wright of Dayton, OH, not only were the first to fly a powered
      aircraft, but also pioneered many human factors considerations. While others
      tried to develop aircraft with a high degree of aerodynamic stability, the
      Wrights intentionally designed unstable aircraft with "cerebralized" control
      modeled on bird flight. During 1901-03, the brothers worked with large gliders at
      Kill Devil Hills, near Kitty Hawk, NC, to develop the first practical human
      interactive controls for aircraft pitch, roll, and yaw. On December 17, 1903,
      they made four controlled, powered flights over the dunes at Kitty Hawk with
      their Wright Flyer. During the next 2 yr, the Wrights made numerous flights in
      the Wright Flyers II and III at Huffman Prairie near Dayton. They later developed
      practical in-flight control of engine power, plus an angle-of-attack sensor and
      stick-pusher that reduced pilot workload. The brothers' flight demonstrations in
      the U.S. and Europe during 1908-09 awakened the world to the new age of
      controlled flight. Orville was the first aviator to use a seat belt. He also
      introduced a rudder boost/trim control that gave the pilot greater control
      authority. The Wrights' flight training school in Dayton included a flight
      simulator of their own design. The Wrights patented their practical airplane and
      flight control concepts, many of which are still in use today.

PMID- 14960059
TI  - This month in aerospace medicine history--February 2004.

PMID- 14960060
TI  - The history of the Aerospace Physiology Society--part III.

PMID- 14960061
TI  - Fizeau interferometer for global astrometry in space.
AB  - We discuss the design and the performance of a Fizeau interferometer with a long
      focal length and a large field of view that is well suited for a global
      astrometry space mission. Our work focuses on the geometric optimization and
      minimization of aberration of such an astrometric interferometer, which is able
      to observe astronomical targets down to the visual magnitude (mag) mv = 20 mag,
      with an accuracy in the measurements of 10 micro-arcseconds at mv = 15 mag. We
      assume a mission profile similar to that of the Global Astrometric Interferometer
      for Astrophysics mission of the European Space Agency. In this framework, data
      acquisition is performed by an array of CCDs working in time-delay integration
      mode. Optical aberrations, particularly distortion and coma, play a crucial role
      in the efficiency of this technique. We present a design solution that meets the
      requirements for the best possible exploitation of the time-delay integration
      mode over a field of view of 0.7 degrees x 0.7 degrees.

PMID- 14960062
TI  - Measuring seeing with a Shack-Hartmann wave-front sensor during an active-optics
      experiment.
AB  - We describe the measurement of atmospheric enclosure seeing along a 120-m light
      path by use of a Shack-Hartmann wave-front sensor (S-H WFS) for the first time to
      our knowledge in the Large Sky Area Multi-Object Fiber Spectroscopic Telescope
      (LAMOST) outdoor active-optics experiment system, based on the differential image
      motion method and a S-H WFS. Seeing estimates that were gained with the S-H WFS
      were analyzed and found to be in close agreement with the actual seeing
      conditions, the estimates of refractive-index structure constant, and the thin
      mirror active optics results, which usually include the shape sensing precision
      and the active correction precision of the experimental system. Finally, some
      countermeasures against poor seeing conditions were considered and adopted.

PMID- 14960063
TI  - Intuitive diffraction model for multistaged optical systems.
AB  - A simplified framework is motivated in which many diffraction effects can be
      treated, especially in multistaged optical systems. The results should be
      especially helpful for short wavelengths and broad-band sources, for which
      numerical calculations can be most difficult.

PMID- 14960064
TI  - Simple high-resolution wavelength monitor based on a fiber Bragg grating.
AB  - A compact and low-cost device for monitoring the peak wavelength of single-peak
      spectral distributions is presented. The system is based on the transmission
      properties of a fiber Bragg grating when its period is modulated. Different types
      of optical signal, such as the emission of distributed-feedback lasers and the
      reflection of a broadband optical source produced by fiber gratings used in
      sensor systems, can be measured with this device. We demonstrate that a high
      wavelength resolution of micro 1 pm can be achieved and that our proposal can be
      used for real-time monitoring.

PMID- 14960065
TI  - Polarization-based compensation of astigmatism.
AB  - One approach to aberration compensation of an imaging system is to introduce a
      suitable phase mask at the aperture plane of an imaging system. We utilize this
      principle for the compensation of astigmatism. A suitable polarization mask used
      on the aperture plane together with a polarizer-retarder combination at the input
      of the imaging system provides the compensating polarization-induced phase steps
      at different quadrants of the apertures masked by different polarizers. The
      aberrant phase can be considerably compensated by the proper choice of a
      polarization mask and suitable selection of the polarization parameters involved.
      The results presented here bear out our theoretical expectation.

PMID- 14960066
TI  - Determination of refractive indices of opaque rough surfaces.
AB  - The refractive indices of optical materials are usually determined from
      spectrophotometric and ellipsometric measurements of specular beams. When the
      roughness of the interfaces increases, the energy in the specularly reflected and
      transmitted beams decreases and scattering becomes predominant. For strong
      roughness (compared to the incident wavelength) a surface does not exhibit
      specular reflection or transmission, making difficult the determination of the
      refractive index. We describe two techniques, based on scattering measurements,
      that one can use to determine the refractive indices of opaque inhomogeneous
      media.

PMID- 14960067
TI  - Measurement of the influence of dispersion on white-light interferometry.
AB  - White-light interferometry is a well-established method for measuring the height
      profiles of samples with rough as well as with smooth surfaces. Because white
      light interferometry uses broadband light sources, the problem of dispersion
      arises. Because the optical paths in the two interferometer arms cannot be
      balanced for all wavelengths, the white-light correlogram is distorted, which
      interferes with its evaluation. We investigate the influence of setup parameters
      on the shape of the correlogram. Calculated values are compared with experimental
      results.

PMID- 14960068
TI  - Resolving quadrature fringes in real time.
AB  - In many interferometers, two fringe signals can be generated in quadrature. The
      relative phase of the two fringe signals depends on whether the optical path
      length is increasing or decreasing. A system is developed in which two quadrature
      fringe signals are digitized and analyzed in real time with a digital signal
      processor to yield a linear, high-resolution, wide-dynamic-range displacement
      transducer. The resolution in a simple Michelson interferometer with inexpensive
      components is 5 x 10(-13) m Hz(-1/2) at 2 Hz.

PMID- 14960069
TI  - Micromachined arrays of cantilevered glass probes.
AB  - We describe the fabrication and characterization of cantilevered glass probe
      arrays. Individual probes have tapered shafts that are 175 microm square at the
      base and 200 nm square at the pyramidal tip. Each array contains as many as eight
      probes 10-20 mm long at 450-microm center-to-center spacing, fabricated from a
      single glass wafer by a combination of dicing and chemical etching. Optical
      signal losses of individual probes were measured to be of the order of 1 dB/cm.
      High-density data storage and page-oriented retrieval are the potential
      applications of the arrays.

PMID- 14960070
TI  - High-performance fluidic adaptive lenses.
AB  - High-performance fluidic lenses with an adjustable focal length spanning a very
      wide range (30 mm to infinite) are demonstrated. We show that the focal length, F
      number, and numerical aperture can be dynamically controlled by changing the
      shape of the fluidic adaptive lens without moving the lens position mechanically.
      The shortest focal length demonstrated is less than 30 mm for a 20-mm lens
      aperture. The fluidic adaptive lens has a nearly perfect spherical profile and
      shows a resolution better than 40 line pairs/mm in a plano-convex structure and
      57 line pairs/mm in a biconvex structure.

PMID- 14960071
TI  - Verification of point-spread-function-based modeling of an extreme-ultraviolet
      photoresist.
AB  - A crucial component of lithographic modeling is the resist. Resists typically
      used at extreme-ultraviolet (EUV) wavelengths are derivatives of deep-ultraviolet
      chemically amplified resists. Models that describe these resists are often very
      complicated and are dependent on a large number of free parameters. Point-spread
      function-based resist modeling serves as a simple alternative. I show this type
      of modeling to be a viable technique at EUV wavelengths by directly comparing
      modeling results with a variety of printing metrics, including process windows
      and isodense bias.

PMID- 14960072
TI  - Overlapped woodpile photonic crystals.
AB  - Woodpile photonic crystals are derived from a diamond lattice by modification of
      the unit cell according to layer-by-layer fabrication convenience. The
      fabrication may be simplified even more if the overlap between adjacent layers is
      allowed. Here we describe the fabrication of such an overlapped-woodpile crystal.
      Its optical characteristics are studied numerically, and the existence of a
      photonic bandgap for specific parameters is demonstrated.

PMID- 14960074
TI  - Control of reflectance of liquid droplets by means of electrowetting.
AB  - It has recently been noted that hemispherical structures have useful reflection
      characteristics. We describe a new application that makes use of these
      characteristics by controlling the reflectance of a surface composed of an array
      of hemispherical liquid droplets. In this system the reflectance state is
      spatially controlled through the use of electrowetting to alter the shape of an
      array of droplets. This may have an application in the field of electronic image
      displays.

PMID- 14960073
TI  - Analysis and design of optical systems by use of sensitivity analysis of skew ray
      tracing.
AB  - Optical systems are conventionally evaluated by ray-tracing techniques that
      extract performance quantities such as aberration and spot size. Current optical
      analysis software does not provide satisfactory analytical evaluation functions
      for the sensitivity of an optical system. Furthermore, when functions oscillate
      strongly, the results are of low accuracy. Thus this work extends our earlier
      research on an advanced treatment of reflected or refracted rays, referred to as
      sensitivity analysis, in which differential changes of reflected or refracted
      rays are expressed in terms of differential changes of incident rays. The
      proposed sensitivity analysis methodology for skew ray tracing of reflected or
      refracted rays that cross spherical or flat boundaries is demonstrated and
      validated by the application of a cat's eye retroreflector to the design and by
      the image orientation of a system with noncoplanar optical axes. The proposed
      sensitivity analysis is projected as the nucleus of other geometrical optical
      computations.

PMID- 14960075
TI  - Validating the assumption to the interference approximation by use of
      measurements of absorption efficiency and hindered scattering in dense
      suspensions.
AB  - Frequency domain photon migration (FDPM) measurements were employed to accurately
      quantify optical properties of both the suspending fluid and particles within
      dense polystyrene suspensions of 143- or 226-nm mean diameter at varying
      concentrations (5-30% by volume). The measured absorption coefficients varied
      linearly with particle volume fraction whereas the isotropic scattering
      coefficients varied nonlinearly in agreement with the prediction that utilizes
      the hard-sphere structure factor model. These results validate the interference
      approximation of light scattering to describe light propagation accurately within
      dense suspensions. Furthermore, owing to the accuracy of FDPM absorption
      measurements, the imaginary refractive indices for both particles and their
      suspending fluid were determined and were found to compare favorably with
      literature values.

PMID- 14960076
TI  - Interferometric monitoring of dip coating.
AB  - Dip-coated films, which are widely used in the coating industry, are usually
      measured by capacitive methods with micrometric precision. For the first time to
      our knowledge, we have applied an interferometric determination of the evolution
      of thickness in real time to nonvolatile Newtonian mineral oils with several
      viscosities and distinct dip withdrawing speeds. The evolution of film thickness
      during the process depends on time as t(-1/2), in accordance with a simple model.
      Comparison with measured results with an uncertainty of +/- 0.007 microm) showed
      good agreement after the initial steps of the process had been completed.

PMID- 14960077
TI  - Analysis of hyperspectral fluorescence images for poultry skin tumor inspection.
AB  - We present a hyperspectral fluorescence imaging system with a fuzzy inference
      scheme for detecting skin tumors on poultry carcasses. Hyperspectral images
      reveal spatial and spectral information useful for finding pathological lesions
      or contaminants on agricultural products. Skin tumors are not obvious because the
      visual signature appears as a shape distortion rather than a discoloration.
      Fluorescence imaging allows the visualization of poultry skin tumors more easily
      than reflectance. The hyperspectral image samples obtained for this poultry tumor
      inspection contain 65 spectral bands of fluorescence in the visible region of the
      spectrum at wavelengths ranging from 425 to 711 nm. The large amount of
      hyperspectral image data is compressed by use of a discrete wavelet transform in
      the spatial domain. Principal-component analysis provides an effective compressed
      representation of the spectral signal of each pixel in the spectral domain. A
      small number of significant features are extracted from two major spectral peaks
      of relative fluorescence intensity that have been identified as meaningful
      spectral bands for detecting tumors. A fuzzy inference scheme that uses a small
      number of fuzzy rules and Gaussian membership functions successfully detects skin
      tumors on poultry carcasses. Spatial-filtering techniques are used to
      significantly reduce false positives.

PMID- 14960078
TI  - Trivariate characteristics of intensity fluctuations for heavily saturated
      optical systems.
AB  - Trivariate cumulants of intensity fluctuations have been computed starting from a
      trivariate intensity probability distribution function, which rests on the
      assumption that the variation of intensity has a maximum entropy distribution
      with the constraint that the total intensity is constant. The assumption holds
      for optical systems such as a thin, long, mirrorless gas laser amplifier where
      under heavy gain saturation the total output approaches a constant intensity,
      although intensity of any mode fluctuates rapidly over the average intensity. The
      relations between trivariate cumulants and central moments that were needed for
      the computation of trivariate cumulants were derived. The results of the
      computation show that the cumulants have characteristic values that depend on the
      number of interacting modes in the system. The cumulant values approach zero when
      the number of modes is infinite, as expected. The results will be useful for
      comparison with the experimental triavariate statistics of heavily saturated
      optical systems such as the output from a thin, long, bidirectional gas laser
      amplifier.

PMID- 14960079
TI  - Reduction of the effect of aberrations in a joint-transform correlator.
AB  - We report the study of the influence of optical aberrations in a joint-transform
      correlator: The wave aberration of the optical system is computed from data
      obtained by ray tracing. Three situations are explored: We consider the
      aberration only in the first diffraction stage (generation of power spectrum),
      then only in the second (transformation of the power spectrum into correlation),
      and finally in both stages simultaneously. The results show that the quality of
      the correlation is determined mostly by the aberrations of the first diffraction
      stage and that we can optimize the setup by moving the cameras along the optical
      axis to a suitable position. The good agreement between the predicted data and
      the experimental results shows that the method explains well the behavior of
      optical diffraction systems when aberrations are taken into account.

PMID- 14960080
TI  - Moire interferogram phase extraction: a ridge detection algorithm for continuous
      wavelet transforms.
AB  - We present a procedure using continuous wavelet transforms (CWTs) to extract the
      phase information from moire interferograms. The relationship between precise
      ridge detection of the two-dimensional CWT magnitude map and accurate phase
      extraction is detailed. A cost function is introduced for the adaptive selection
      of the ridge, and a computationally inexpensive implementation of the cost
      function ridge detection algorithm is explored with dynamic programming
      optimization. The results of the proposed ridge detection algorithm on actual
      interferograms are illustrated. Moreover, the resulting extracted phase is
      demonstrated to be smooth and accurate. As a result, the sensitivity of the moire
      interferometry method is improved to obtain a pixel-by-pixel in-plane strain
      distribution map.

PMID- 14960081
TI  - Optical implementation of the hopfield neural network with matrix gratings.
AB  - We propose a new method for the optical implementation of the Hopfield neural
      network with a universal tool. The tool is a matrix grating constituted with a
      group of element gratings. The algorithms for designing a matrix grating are
      proposed, and a matrix grating is created to execute recognition experiments by
      use of the Hopfield neural network. The experimental results demonstrate that the
      proposed method performs well. The stability of the light efficiencies of
      different optical components used in optical networks is also considered.

PMID- 14960082
TI  - Programmable optoelectronic neural network for optimization.
AB  - An optoelectronic neural network is presented that is designed to solve the
      assignment problem--or any similar optimization task given minimal adjustment--in
      both crossbar and banyan packet switches. We examine the design decisions made at
      the hardware, software, and algorithmic levels and indicate the associated effect
      on the system as a whole. Clearly detailed experimental results show the system's
      robustness and performance due to the particular optoelectronic-algorithm
      combination used. The integration and packaging of such a system are also briefly
      discussed.

PMID- 14960083
TI  - Optical characteristics of a refractive optical attenuator with respect to the
      wedge angles of a silicon optical leaker.
AB  - We design, fabricate, and characterize the micromachined refractive variable
      optical attenuator (VOA) with a wedge-shaped silicon optical leaker (SOL). The
      vertical structures of the VOA device can be simply fabricated by deep reactive
      ion etching with no sidewall metallization, and the 8 degrees angled fibers are
      employed for a high return loss even in air-ambient conditions. The SOL
      successively transmits and refracts part of the incident light far outside the
      acceptance angle of the output fiber, showing an effective optical attenuation.
      The fabricated VOA gives high optical performances, such as a response time of 6
      ms, a return loss of 39 dB, an insertion loss of 0.6 dB, an attenuation range of
      43 dB, and a polarization-dependent loss (PDL) of a 10% attenuation level,
      including a wavelength-dependent loss. The optical characteristics of the VOA are
      also theoretically investigated with respect to the wedge angles of the SOL. The
      experimental characteristics are in good agreement with the theoretical values
      calculated, considering light scattered from the endface of an optical fiber and
      sidewall of the SOL. The PDL estimation was confirmed especially to sufficiently
      explain the fundamental characteristic of the PDL for the refractive VOA.

PMID- 14960084
TI  - Measuring ultrashort optical pulses in the presence of noise: an empirical study
      of the performance of spectral phase interferometry for direct electric field
      reconstruction.
AB  - We have measured the performance of a real spectral phase interferometry for
      direct electric field reconstruction (SPIDER) apparatus operating under
      suboptimal conditions. We analyzed the errors in SPIDER's measurements of the
      temporal phases and intensities of 50-fs ultrashort laser pulses as a function of
      the additive noise in the detected signal. It was found that SPIDER performs
      exceptionally well, particularly in the case of additive noise. Specifically, a
      signal with 10% noise yields a pulse that has a mere 2% error in its intensity
      profile and a phase that differs from the nominal value by 0.2 rad. Furthermore,
      we quantified SPIDER's performance with limited detector resolution and as a
      function of signal averaging.

PMID- 14960085
TI  - Excitation nonlinearities in emission reabsorption laser-induced fluorescence
      techniques.
AB  - The effects of the nonlinear behavior of fluorescent intensity with excitation
      intensity on emission reabsorption laser-induced fluorescence (ERLIF) are
      investigated. Excitation nonlinearities arise mainly as a consequence of the
      depletion of the ground-state population stemming from the finite lifetime of
      molecules in the excited state. These nonlinearities hinder proper suppression of
      the excitation intensity information in the fluorescence ratio, degrading
      measurement accuracy. A method for minimizing this effect is presented. This
      method is based on the approximation of the fluorescence intensity nonlinearities
      by a power law. Elevating the two-dimensional fluorescent intensity maps to the
      appropriate exponent allows for proper suppression of excitation intensity in the
      fluorescence ratio. An overview of the principles and constitutive equations
      behind ERLIF film-thickness measurements, along with a characterization of the
      fluorescence's nonlinear behavior, is presented. The power law approximation and
      processing scheme used to mitigate this behavior are introduced. Experimental
      proof of the validity of the approximation and processing scheme is provided.

PMID- 14960086
TI  - Sensitivity studies for space-based measurement of atmospheric total column
      carbon dioxide by reflected sunlight.
AB  - The feasibility of making space-based carbon dioxide (CO2) measurements for
      global and regional carbon-cycle studies is explored. With the proposed detection
      method, we use absorption of reflected sunlight near 1.58 microm. The results
      indicate that the small (degrees 1%) changes in CO2 near the Earth's surface are
      detectable provided that an adequate sensor signal-to-noise ratio and spectral
      resolution are achievable. Modification of the sunlight path by scattering of
      aerosols and cirrus clouds could, however, lead to systematic errors in the CO2
      column retrieval; therefore ancillary aerosol and cloud data are important to
      reduce errors. Precise measurement of surface pressure and good knowledge of the
      atmospheric temperature profile are also required.

PMID- 14960087
TI  - Calculated refractivity of water vapor and moist air in the atmospheric window at
      10 microm.
AB  - The HITRAN 2000 database of infrared line transitions has been used to calculate
      the dispersion coefficient of water vapor at room temperature in the atmospheric
      window up to 25 microm, confirming an equivalent earlier compilation [Infrared
      Phys. 26, 371 (1986)]. I complement this line set by using an previously
      published ultraviolet pseudospectrum [J. Chem. Phys. 68, 1426 (1978)] to improve
      coverage of the near infrared. The effect of admixtures of abundant nitrogen,
      oxygen, and carbon dioxide is predicted on the same calculational basis to
      synthesize the air representative of the mountain that hosts the Very Large
      Telescope Interferometer and is found to be small compared with the dominant role
      of water at wavelengths above 3 microm.

PMID- 14960088
TI  - Fabrication and analysis of a low-loss in-fiber active polymer waveguide.
AB  - We present a method for fabricating an in-fiber electro-optic polymer waveguide
      within a D-shaped optical fiber. A combined process of selective chemical etching
      and spin coating creates a 2-cm in-fiber poly(methyl methacrylate)-DR1 dye
      polymer waveguide section with an overall insertion loss of micro 1.6 dB at 1550
      nm. Numerical simulations show that, for in-fiber polymer waveguides to have low
      loss, the polymer layer's thickness must be kept below a certain value so that it
      will not support slab waveguide modes. Long transition regions between the
      unetched fiber and the polymer waveguide section also reduce loss. We analyze the
      efficiency of an in-fiber polymer waveguide by simulating its theoretical
      performance as an electro-optic modulator.

PMID- 14960089
TI  - Nonstoichiometric silica mask for fabricating reverse proton-exchanged waveguides
      in lithium niobate crystals.
AB  - Producing channel waveguides requires a photolithographic mask, but the standard
      technique of using thermally evaporated metal films for proton exchange has
      proved to be unsuitable for withstanding the rather aggressive process of reverse
      proton exchange. We report the fabrication of a nonstoichiometric silica mask by
      ion-plating plasma-assisted deposition. This mask is strong enough to resist both
      direct and reverse proton exchange and is also compatible with anisotropic dry
      etching for patterning the mask and with electric field poling. Our technique is
      a practical alternative to the use of SiO2 sputtered masks.

PMID- 14960090
TI  - Iterative method for the design of a dual-phase-conjugation-mirror resonator with
      multiple apertures.
AB  - Apertures have been used to select the low-order transverse modes in resonators.
      The additional diffraction losses result in a change in the transverse-mode
      structure, and the presence of apertures inside a resonator generally distorts
      the mode shape. The optimization of a multiple-aperture resonator demands an
      approach that differs from the conventional method in which the mode theory is
      used. We demonstrate an iterative design method to find optimal phase profiles
      for the reflector surfaces to build a resonator with multiple apertures to
      produce a lowest-order mode with much smaller diffraction loss and to satisfy the
      phase-conjugation conditions at the mirrors. The results are compared with
      conventional stable resonators, and we show that substantial improvement in round
      trip loss and beam quality can also be obtained.

PMID- 14960091
TI  - Generation of uniform light by use of diode lasers and a truncated paraboloid
      with a Lambertian scatterer.
AB  - Uniform illumination was generated by use of a large number of diode laser
      emitters and a single nonimaging paraboloid with a Lambertian scatterer in the
      truncation plane. Laser light traverses a path toward the Lambertian surface and
      back by total internal reflection. An overall efficiency of 69% was demonstrated.
      Improvements that would increase the efficiency to more than 85% are suggested.
      The illuminated area is circular, with 14-mm diameter. The spatial nonuniformity
      of the beam profile is less than +/- 2%.

PMID- 14960092
TI  - Sellmeier's equation and the expression of the thermal refractive-index
      coefficient for a Nd0.007Gd0.993VO4 crystal.
AB  - The principal refractive indices of a Nd0.007Gd0.993VO4 crystal for wavelengths
      of 0.488, 0.6328, 1.064, 1.0795, and 1.3414 microm under the temperature range of
      20-170 degrees C are measured by the autocollimation method, and the Sellmeier's
      equation and the expression of the thermal refractive-index coefficient are then
      obtained. The reliability of these results is checked by comparing the calculated
      values with the measured values for the measured wavelengths and the temperature
      region, as well as with the published values by Studenikin et al. [Quantum
      Electron. 25, 1162-1165 (1995)] for wavelengths of 0.491, 0.546, 0.578, 0.632,
      0.808, and 1.062 microm at 20 degrees C. In addition, the birefringence and the
      thermal coefficient of the birefringence were obtained by measured results. The
      results show that the birefringence is larger than that of a YVO4 crystal and
      that the thermal coefficient of birefringence is less than that of a YVO4
      crystal. Therefore it can be expected that the GdVO4 crystal is not only an
      excellent laser crystal but also an excellent birefringent crystal used in a
      modern optical transmission system as a passive fiber-optic component.

PMID- 14960093
TI  - Aerosol lidar intercomparison in the framework of the EARLINET project. 1.
      Instruments.
AB  - In the framework of the European Aerosol Research Lidar Network to Establish an
      Aerosol Climatology (EARLINET), 19 aerosol lidar systems from 11 European
      countries were compared. Aerosol extinction or backscatter coefficient profiles
      were measured by at least two systems for each comparison. Aerosol extinction
      coefficients were derived from Raman lidar measurements in the UV (351 or 355
      nm), and aerosol backscatter profiles were calculated from pure elastic
      backscatter measurements at 351 or 355, 532, or 1064 nm. The results were
      compared for height ranges with high and low aerosol content. Some systems were
      additionally compared with sunphotometers and starphotometers. Predefined maximum
      deviations were used for quality control of the results. Lidar systems with
      results outside those limits could not meet the quality assurance criterion. The
      algorithms for deriving aerosol backscatter profiles from elastic lidar
      measurements were tested separately, and the results are described in Part 2 of
      this series of papers [Appl. Opt. 43, 977-989 (2004)]. In the end, all systems
      were quality assured, although some had to be modified to improve their
      performance. Typical deviations between aerosol backscatter profiles were 10% in
      the planetary boundary layer and 0.1 x 10(-6) m(-1) sr(-1) in the free
      troposphere.

PMID- 14960094
TI  - Aerosol lidar intercomparison in the framework of the EARLINET project. 2.
      Aerosol backscatter algorithms.
AB  - An intercomparison of aerosol backscatter lidar algorithms was performed in 2001
      within the framework of the European Aerosol Research Lidar Network to Establish
      an Aerosol Climatology (EARLINET). The objective of this research was to test the
      correctness of the algorithms and the influence of the lidar ratio used by the
      various lidar teams involved in the EARLINET for calculation of backscatter
      coefficient profiles from the lidar signals. The exercise consisted of processing
      synthetic lidar signals of various degrees of difficulty. One of these profiles
      contained height-dependent lidar ratios to test the vertical influence of those
      profiles on the various retrieval algorithms. Furthermore, a realistic incomplete
      overlap of laser beam and receiver field of view was introduced to remind the
      teams to take great care in the nearest range to the lidar. The intercomparison
      was performed in three stages with increasing knowledge on the input parameters.
      First, only the lidar signals were distributed; this is the most realistic stage.
      Afterward the lidar ratio profiles and the reference values at calibration height
      were provided. The unknown height-dependent lidar ratio had the largest influence
      on the retrieval, whereas the unknown reference value was of minor importance.
      These results show the necessity of making additional independent measurements,
      which can provide us with a suitable approximation of the lidar ratio. The final
      stage proves in general, that the data evaluation schemes of the different groups
      of lidar systems work well.

PMID- 14960095
TI  - Clinical research in homeopathy: randomised, controlled or outcome studies?

PMID- 14960096
TI  - An observational study of patients receiving homeopathic treatment.
AB  - BACKGROUND: Observational studies have recently contributed useful information to
      the debate about the utility of homeopathic treatment in everyday practice. AIM:
      To gather data about routine homeopathic general practice. SETTING: Eighty
      general medical practices in Belgium where physicians were members of the Unio
      Homoeopathica Belgica. METHODS: All patients and their physicians visiting the
      practices on a specified day completed a questionnaire. RESULTS: A total of 782
      patients presented with diseases of all major organ systems which were of
      sufficient severity to interfere with daily living in 78% of cases. Compared to
      previous conventional treatment, patients reported that consultations were much
      longer but costed less. One or more conventional drug treatments were
      discontinued in over half (52%) of the patients: CNS (including psychotropic)
      drugs (21%), drugs for respiratory conditions (16%) and antibiotics (16%).
      Conventional drugs were prescribed to about a quarter of patients (27%), mostly
      antibiotics and cardiovascular medication. The antibiotics were almost
      exclusively (95%) used to treat respiratory infections. Prescription costs
      (including conventional medicines) were one-third of the general practice
      average. Patients' satisfaction with their homeopathic treatment was very high
      (95% fairly or very satisfied), and ratings of their previous treatment was much
      lower (20%). The great majority (89%) said that homeopathy had improved their
      physical condition; 8.5% said that it had made no difference, 2.4% said that
      homeopathy had worsened their condition. Physicians' ratings of improvement were
      similar. Previous conventional treatment had improved 13% of patients, made no
      difference to 32%, and had worsened the condition of over half (55%). A similar
      pattern was seen for psychological symptoms. CONCLUSIONS: Patients were very
      satisfied with their homeopathic treatment, both they and their physicians
      recorded significant improvement. Costs of homeopathic treatment were
      significantly lower than conventional treatment, and many previously prescribed
      drugs were discontinued.

PMID- 14960097
TI  - Action of Causticum in inflammatory models.
AB  - The anti-inflammatory effect of Causticum was evaluated using acute and chronic
      inflammatory models in vivo. The administration of concentrated Causticum
      solution into the hind paw of rats produced an inflammatory reaction with oedema
      formation within the first hour, showing that Causticum acts as an oedematogenic
      agent. Carrageenin induced rat paw oedema was significantly inhibited (P<0.05) in
      the group treated with Causticum 30cH solution compared to control. Groups
      treated with potentized Causticum (6cH, 12cH, 30cH and 200cH), showed significant
      inhibition (P<0.05) of the inflammation pre-induced by carrageenin. However pre
      treatment with Causticum 30cH for 6 days (0.5 ml, daily) did not significantly
      inhibit granulation using an implantation method.

PMID- 14960098
TI  - Evaluation of a homeopathic complex in the clinical management of udder diseases
      of riverine buffaloes.
AB  - We report an uncontrolled observational study of the treatment of udder diseases
      of buffalo, using a homeopathic complex medicine. Mastitis is an economically
      important disease of buffaloes. In India economic losses due to mastitis are
      estimated at 526 million US dollars annually. Conventional veterinary treatment
      relies on costly antibiotics; cure rate is only 60% in field conditions with a
      problem of milk residues. The present investigation was undertaken to evaluate
      the effectiveness of a homeopathic complex in the management of clinical udder
      health problems of riverine buffaloes. Cases of subclinical mastitis were
      excluded from the study. A total of 102 mastitic quarters (fibrosed--40,
      nonfibrosed--62) and five cases each of blood in milk and udder oedema in
      lactating buffaloes were treated with a homeopathic complex consisting of
      Phytolacca 200c, Calcarea fluorica 200c, Silicea 30c, Belladona 30c, Bryonia 30c,
      Arnica 30c, Conium 30c and Ipecacuanha 30c. The diagnosis of udder diseases and
      recovery criterion was based on physical examination of udder and milk and
      CMT/WST score. Bacteriological analysis and somatic cell count were not
      performed. Treatment was 80 and 96.72% effective in cases of fibrotic mastitis
      and nonfibrosed mastitis respectively. Recovery period was 21-42 days (fibrosed)
      and 4-15 days (nonfibrosed). Udder oedema and blood in milk responded favourably
      in 2-5 days. Cost of treatment was 0.07 US dollars per day. The homeopathic
      complex medicine may be effective and economical in the management of udder
      health problems of buffaloes. Definitive conclusions are premature due to the
      limited number of observations and lack of control group.

PMID- 14960099
TI  - The pitfalls of clinical case research: lessons from the Delphi Project.
AB  - Delphi is a project to make high-quality cases treated with homeopathy available
      for study. The project encountered a number of major difficulties including small
      numbers of cases submitted, ethical problems and problems of analysis. The nature
      of these problems and possible solutions are discussed.

PMID- 14960100
TI  - The toxicology of Latrodectus tredecimguttatus: the Mediterranean Black Widow
      spider.
AB  - The symptomatology of envenomation by the Mediterranean Black Widow Spider,
      Latrodectus tredecimguttatus, is reviewed. The results confirm the hypothesis
      that the homeopathic remedy, Tarentula hispanica, is derived from this spider,
      not from the Wolf spider, Lycosa tarentula.

PMID- 14960101
TI  - Patient-practitioner-remedy (PPR) entanglement. Part 4. Towards classification
      and unification of the different entanglement models for homeopathy.
AB  - The possibility of classifying and unifying some of the recent entanglement
      models for homeopathy is discussed. Unification involves combining the previous
      GHZ/WQT-based entanglement model, itself a fusion of Greenberger-Horne-Zeilinger
      (GHZ) three-particle entanglement and a generalised version of quantum theory,
      called Weak Quantum Theory (WQT), with Walach's semiotic model involving double
      entanglement. The new combined model invokes a 'geometry' of patient-practitioner
      remedy (PPR) entanglement embedded in a therapeutic state space.

PMID- 14960102
TI  - Kent and quantum mechanics.

PMID- 14960103
TI  - Trifolium pratense for breast disease: a case series.
AB  - A series of cases in which Trifolium pratense was used in breast disease with
      hyperoestrogenic symptoms is reported. Several patients with cystic mastosis and
      breast cancer appeared to do well. The 'picture' of Trifolium is discussed.

PMID- 14960104
TI  - Elaps in advanced pathology--a case study.
AB  - The case of a patient with severe complications after rectal adenocarcinoma
      surgery is reported. Homeopathic treatment was selected on the basis of
      individualization of symptoms ('minimum syndrome of maximum value') and
      prescribed in Korsakovian potencies. It is discussed what it may be expected in
      the treatment of severely ill patients.

PMID- 14960105
TI  - 20 years ago: British Homoeopathic Journal, January 1984.

PMID- 14960106
TI  - The benefits of Arnica.

PMID- 14960107
TI  - Physical analysis of ultramolecular dilutions.

PMID- 14960108
TI  - Time-frequency analysis of SEMG--with special consideration to the interelectrode
      spacing.
AB  - The surface electromyogram (SEMG) is a complex, nonstationary signal. The
      spectrum of the SEMG is dependent on the force of contraction being generated and
      other factors like muscle fatigue and interelectrode distance (IED). The spectrum
      of the signal is time variant. This paper reports the experimental research
      conducted to study the influence of force of muscle contraction and IED on the
      SEMG signal using time-frequency (T-F) analysis. Two T-F techniques have been
      used: Wigner-Ville distribution (WVD) and Choi-Williams distribution (CWD). The
      experiment was conducted with the help of ten healthy volunteers (five males and
      five females) who performed isometric elbow flexions of the active right arm at
      20%, 50%, and 80% of their maximal voluntary contraction. The SEMG signal was
      recorded using surface electrodes placed at a distance of 18 and 36 mm over
      biceps brachii muscle. The results indicate that the two distributions were
      spread out across the frequency range at smaller IED. Further, regardless of the
      spacing, both distributions displayed increased spectral compression with time at
      higher contraction level.

PMID- 14960109
TI  - A sensorized thumb for force closed-loop control of hand neuroprostheses.
AB  - In this paper, we presented a sensorized thumb based on a matrix of
      piezoresistive force sensors, with an acquisition unit and a special wearing
      support. The sensor was calibrated and then the device was tested during
      different tasks simulating activities of daily living performed by seven able
      bodied subjects. By means of these experiments, we verified that the device
      proposed can be used to extract force information during grasp. In fact, the
      device was able to provide useful force information in the 98% of the trials with
      a good repeatability during all the different conditions. Moreover, we evaluated
      the patterns obtained during the different grasping tasks. The palmar grasps were
      performed in a similar manner, whereas the lateral pinch and the spherical volar
      grip were more different. This device can provide force information with good
      performance and acceptability and it can be used for force closed-loop control of
      hand neuroprostheses.

PMID- 14960110
TI  - Enabling computer decisions based on EEG input.
AB  - Multilayer neural networks were successfully trained to classify segments of 12
      channel electroencephalogram (EEG) data into one of five classes corresponding to
      five cognitive tasks performed by a subject. Independent component analysis (ICA)
      was used to segregate obvious artifact EEG components from other sources, and a
      frequency-band representation was used to represent the sources computed by ICA.
      Examples of results include an 85% accuracy rate on differentiation between two
      tasks, using a segment of EEG only 0.05 s long and a 95% accuracy rate using a
      0.5-s-long segment.

PMID- 14960111
TI  - Analyzing EEG signals using the probability estimating guarded neural classifier.
AB  - This paper introduces a neural network architecture for classifying feature
      vectors symbolizing portions (or segments) of an electroencephalogram (EEG) trace
      of a human subject. This classification task is the one that is typically
      required when developing a so-called brain-computer interface (BCI), which
      analyzes the EEG signals of a subject in order to "understand" the subject's
      thoughts. However, instead of merely saying which "category of thoughts" (i.e.,
      which class) the respective input feature vector belongs to, the network
      described here estimates the probabilities of an EEG segment being associated
      with each individual class. The network, which is called PeGNC (for probability
      estimating guarded neural classifier), is tested with two kinds of experiments.
      In the first experiment, the alpha-rhythm associated with a human subject closing
      the eyes is detected online with the help of a frequency-based representation.
      Since the EEG signal is, in general, always a mixture of numerous action
      potentials generated simultaneously and it is, thus, very likely that mental
      activities result in overlapping classes, it is reasonable to believe that the
      PeGNC network--which does not select any one single class, but determines
      probability values for each mental category--is particularly suitable for this
      kind of EEG analysis. The second experiment deals with this issue on the basis of
      an offline analysis of simulated data.

PMID- 14960112
TI  - Wavelength and intensity dependence of retinal evoked responses using in vivo
      optic nerve recording.
AB  - We use a whole-animal model and wavelength-selective optical stimulation to
      investigate relationships between optical stimulus characteristics and neural
      signaling. Light-emitting diodes are used to selectively stimulate rod and cone
      pathways in Rana pipiens. A suction electrode is used to make in vivo
      measurements of the compound action potential from the optic nerve as the
      wavelength and intensity of the stimulus is varied. Our results demonstrate that
      the cone and rod pathways can be separately stimulated and analyzed with our
      method and, thus, provide a means to model the response of such pathways to more
      complex stimuli.

PMID- 14960113
TI  - Foot placement alters the mechanisms of postural control while standing and
      reaching.
AB  - This study investigated the effects of altering foot placement on the strategies
      used by able-bodied subjects to perform reaching tasks while standing. The
      motivation for this study was to consider the results in the context of a person
      with a spinal cord injury using a functional neuromuscular stimulation (FNS)
      system to stand while reaching. Three foot placement conditions were compared as
      subjects reached to the left, right, and center. Centers of pressure (COP), joint
      angles, and joint moments were calculated as postural parameters using force
      platform and video marker data. Side-by-side and wide foot placements resulted in
      similar postural parameters. In contrast, the modified tandem stance (feet spaced
      at pelvic width with one foot shifted forward) resulted in anterior/posterior COP
      excursions that were larger in magnitude and more consistent across reach
      directions when compared to the other foot placement conditions. Furthermore, the
      movement patterns used during the tandem stance were more consistent and may be
      more readily achievable with FNS than the movement patterns utilized with the
      side-by-side and wide stances. These results suggest that the modified tandem
      stance may enhance the functionality of FNS standing systems and may also be
      useful in other standing rehabilitation programs.

PMID- 14960114
TI  - A rapid speech synthesizing software on a PDA for Japanese with speech
      impairments.
AB  - We developed a Japanese-language, rapid synthesizing software application for use
      on a personal digital assistant. It has an unrestricted vocabulary and can
      synthesize words and sentences within 3 s. Eight hundred common sentences and
      words are preregistered. By touching the first character at the head of a
      preregistered sentence or word from an on-screen Kana (Japanese alphabet) chart,
      the user can select the sentence or word to be spoken. Characters on the Kana
      chart can also be input sequentially. Two Japanese subjects with speech
      impairments rated the device highly for its portability and quick response.
      Whereas communication previously had to be done by writing or sign language, it
      was easy for listeners with or without specialized training in communication with
      persons with speech impairments to understand the output from this device, making
      conversation easier which, in turn, improved the quality of life and social
      activity of these persons with speech impairments.

PMID- 14960115
TI  - Vibrotactile display coding for a balance prosthesis.
AB  - Preliminary experiments have demonstrated the potential usefulness of a precursor
      balance prosthesis that displays the tilt of the subject using tactile vibrators
      (tactors) which are in contact with the subject's skin. The device consists of a
      motion sensing system mounted on the head or body whose signals are converted
      into estimates of head or body tilt. Tilt is displayed to the subject by coding
      the tilt estimate into signals that are sent to the tactors using one of several
      schemes. Because full blown, end-to-end balance experiments are relatively time
      consuming and expensive, and because there are many possible display schemes, we
      have developed a quantitative means to evaluate the display step separately. We
      used a modified version of the manual control critical tracking task (CTT) to
      help us make an initial selection of the more promising vibrotactile display
      schemes for further evaluation. The classic CTT is a compensatory form of
      tracking in which the operator attempts to control an increasingly unstable
      system using a joystick to regulate a tracking error signal (system minus
      joystick) that is visually displayed as a dot on a cathode ray tube. Our
      modification added vibrotactile display of the error signal. For a given subject
      and vibrotactile display scheme, the level of difficulty at which the subjects
      lost control, called the critical lambda (lambda(c)), was highly repeatable. Four
      different coding schemes were evaluated using an array of 16 vibrators that were
      attached to the lower backs of 11 healthy subjects. The first scheme, called
      interval-based coding, modulated the interval between pulses that were sent to
      single tactors mounted on the subject's right and left side. A greater tracking
      error magnitude was displayed as a faster pulse rate. A positive error was
      displayed on the right side while a negative one was displayed on the left. The
      remaining three schemes, called position-based coding, used a horizontal row of
      14 tactors. Tracking error magnitude was mapped to position of the activated
      vibrator so that an error near zero corresponded to a vibrator near the center of
      the back. The three position-based schemes tested used three, four, or seven
      tactors per side. Averaged over all subjects, the value of lambda(c) for the
      interval-based scheme was significantly less than it was for each of the three
      position-based schemes. There was no significant change in lambda(c) as the
      number of position-based tactors was increased from three to seven per side. The
      prediction of better actual balance performance using position-based relative to
      interval-based vibrotactile display was validated by a preliminary study of six
      normal subjects that compared the body sway produced during quiet standing while
      providing head tilt estimates using both display modes. Our study provides basic
      characterization using lambda(c) for several vibrotactile display schemes in
      human subjects. The quantitative CTT measure of performance can logically be
      extended to other applications of vibrotactile displays and to other kinds of
      display schemes used for rehabilitation.

PMID- 14960116
TI  - Wavelet analysis of surface electromyography to determine muscle fatigue.
AB  - Muscle fatigue is often a result of unhealthy work practice. It has been known
      for some time that there is a significant change in the spectrum of the
      electromyography (EMG) of the muscle when it is fatigued. Due to the very complex
      nature of this signal however, it has been difficult to use this information to
      reliably automate the process of fatigue onset determination. If such a process
      implementation were feasible, it could be used as an indicator to reduce the
      chances of work-place injury. This research report on the effectiveness of the
      wavelet transform applied to the EMG signal as a means of identifying muscle
      fatigue. We report that with the appropriate choice of wavelet functions and
      scaling factors, it is possible to achieve reliable discrimination of the fatigue
      phenomenon, appropriate to an automated fatigue identification system.

PMID- 14960117
TI  - Stimulation artifact in surface EMG signal: effect of the stimulation waveform,
      detection system, and current amplitude using hybrid stimulation technique.
AB  - The purpose of this study was to investigate the amplitude properties of the
      artifact generated on the recorded surface electromyography (EMG) signals during
      transcutaneous electrical muscle stimulation. The factors which were investigated
      are the shape of the stimulation waveform, the distance of the stimulating
      electrode from the recording system, the interelectrode distance of the detection
      system, the spatial filter used for signal detection, and the stimulation current
      amplitude. Surface EMG signals were recorded during electrical stimulation of the
      biceps brachii motor point with a linear adhesive array of eight electrodes.
      Electrical stimulation was applied with seven stimulation waveforms (mono- and
      biphasic triangular, sinusoidal, and rectangular), generated by a specifically
      designed neuromuscular stimulator with hybrid output stage. The stimulation peak
      current was linearly increased from 0 mA to the maximum tolerated by the subject.
      The detection systems investigated were single and double differential with
      interelectrode distances multiple of 5 mm. Two trials for each contraction were
      performed on three different days. The average rectified artifact values (both
      absolute and normalized with respect to the corresponding M-wave values) were
      computed to investigate the artifact amplitude properties. Results indicated
      that, while the artifact average rectified value, normalized with respect to the
      M-wave amplitude, depended on the distance of the detecting electrodes from the
      stimulation point, it did not depend on the stimulation waveform, on the current
      intensity, on the interelectrode distance, and on the spatial filter. It was
      concluded that, using hybrid stimulation techniques, the selection of particular
      stimulation waveforms, interelectrode distances, or spatial filters has a minor
      effect on the reduction of the artifact when recording M-waves.

PMID- 14960119
TI  - "Virtual keyboard" controlled by spontaneous EEG activity.
AB  - A "virtual keyboard" (VK) is a letter spelling device operated for example by
      spontaneous electroencephalogram (EEG), whereby the EEG is modulated by mental
      hand and leg motor imagery. We report on three able-bodied subjects, operating
      the VK. The ability in the use of the VK varies between 0.85 and 0.5 letters/min
      in error-free writing.

PMID- 14960118
TI  - Sonification of range information for 3-D space perception.
AB  - We present a device that allows three-dimensional (3-D) space perception by
      sonification of range information obtained via a point laser range sensor. The
      laser range sensor is worn by a blindfolded user, who scans space by pointing the
      laser beam in different directions. The resulting stream of range measurements is
      then converted to an auditory signal whose frequency or amplitude varies with the
      range. Our device differs from existing navigation aids for the visually
      impaired. Such devices use sonar ranging whose primary purpose is to detect
      obstacles for navigation, a task to which sonar is well suited due to its wide
      beam width. In contrast, the purpose of our device is to allow users to perceive
      the details of 3-D space that surrounds them, a task to which sonar is ill
      suited, due to artifacts generated by multiple reflections and due to its limited
      range. Preliminary trials demonstrate that the user is able to easily and
      accurately detect corners and depth discontinuities and to perceive the size of
      the surrounding space.

PMID- 14960120
TI  - Noninvasive measurement of torque development in the rat foot: measurement setup
      and results from stimulation of the sciatic nerve with polyimide-based cuff
      electrodes.
AB  - In neural rehabilitation, selective activation of muscles after electrical
      stimulation is mandatory for control of paralyzed limbs. For an evaluation of
      electrode selectivity, a setup to noninvasively measure the force development
      after electrical stimulation in the rat foot was developed. The setup was
      designed in accordance to the anatomical features of the rat model to test the
      isometric torque development at given ankle positions in an intact leg. In this
      paper, the setup design and development is presented and discussed. In a first
      study, the selectivity of small nerve cuffs with 12 electrodes implanted around
      the rat sciatic nerve was investigated. Special attention was drawn to the
      performance of the torque measurement setup in comparison to electrophysiological
      data obtained from compound muscle action potential recordings. Using one cuff
      around the nerve, electrical stimulation on different electrode tripoles led to
      plantarflexion and dorsiflexion of the foot without an a priori alignment of the
      cuff.

PMID- 14960121
TI  - A PC-based system for evaluating the efficacy of the NESS Handmaster orthosis.
AB  - Functional electrical stimulation (FES) is a viable alternative to conventional
      treatments aimed at restoring function and mobility following central nervous
      system (CNS) damage. Muscle contractions are converted into functional activity,
      thus, its wide range of clinical applications. Research efforts are currently
      focused on the development of programmable stimulators that enable the patient to
      perform tasks related to activities of daily living. Herein, we present a PC
      based surface stimulator that enables the user to vary the stimulus waveform and
      the activation sequence of different muscle groups within a wide range of
      options. This instrumentation is not only a development platform for other, more
      sophisticated neuroprostheses, but an essential tool for evaluating the
      rehabilitative efficacy of the NESS Handmaster (NESS Ltd., Israel). Our PC-based
      stimulator reproduces Handmaster motor tasks by selectively activating the five
      muscle groups that control the hand, palmar, and lateral grasps. The stimulator
      is entirely controlled by the plegic patient with the push of a button. The
      ancillary software permits acquisition of up to sixteen analog channels, so that
      feedback signals for closed-loop control of the grasp function can be measured.

PMID- 14960122
TI  - A model-based approach to stabilizing crutch supported paraplegic standing by
      artificial hip joint stiffness.
AB  - The prerequisites for stable crutch supported standing were analyzed in this
      paper. For this purpose, a biomechanical model of crutch supported paraplegic
      stance was developed assuming the patient was standing with extended knees. When
      using crutches during stance, the crutches will put a position constraint on the
      shoulder, thus reducing the number of degrees of freedom. Additional hip-joint
      stiffness was applied to stabilize the hip joint and, therefore, to stabilize
      stance. The required hip-joint stiffness for changing crutch placement and hip
      joint offset angle was studied under static and dynamic conditions. Modeling
      results indicate that, by using additional hip-joint stiffness, stable crutch
      supported paraplegic standing can be achieved, both under static as well as
      dynamic situations. The static equilibrium postures and the stability under
      perturbations were calculated to be dependent on crutch placement and stiffness
      applied. However, postures in which the hip joint was in extension (C postures)
      appeared to the most stable postures. Applying at least 60 N x m/rad hip-joint
      stiffness gave stable equilibrium postures in all cases. Choosing appropriate hip
      joint offset angles, the static equilibrium postures changed to more erect
      postures, without causing instability or excessive arm forces to occur.

PMID- 14960123
TI  - Static and dynamic evaluation of the influence of supplementary hip-joint
      stiffness on crutch-supported paraplegic stance.
AB  - Paraplegic persons can stand with hip-knee-ankle-foot orthoses (HKAFO) and
      crutches. However, current HKAFOs restrict body movement extensively, which may
      impede functional upper-body movements. A more compliant body support using a
      more compliant orthosis or well-controlled functional electrical stimulation
      system may increase freedom of movement to the user, but should not impede
      stability and required arm support. In the current study, we investigated the
      consequences of varying stiffness applied at the hip to postural stability and
      required crutch force during paraplegic stance. Experiments were performed on
      five paraplegic persons with spinal cord lesions varying from T1 to T12. Static
      postures and dynamic responses to perturbations were tested for varying hip
      stiffness and crutch placements. The minimal hip-joint stiffness for stable
      stance appeared to depend on lesion level. In contrast to the predictions of a
      previous modeling study, no statistically significant influences of hip-joint
      stiffness or crutch-to-foot distance on posture and applied crutch forces were
      found. It is hypothesized that the main reasons of this discrepancy are the
      active upper-body efforts the paraplegic HKAFO users are still able to exert and
      the remaining flexibility of the upper trunk and shoulder region, which is
      present despite the restrictions of the orthosis.

PMID- 14960124
TI  - Morse code application for wireless environmental control systems for severely
      disabled individuals.
AB  - Some physically-disabled people with neuromuscular diseases such as amyotrophic
      lateral sclerosis, multiple sclerosis, muscular dystrophy, or other conditions
      that hinder their ability to write, type, and speak, require an assistive tool
      for purposes of augmentative and alternative communication in their daily lives.
      In this paper, we designed and implemented a wireless environmental control
      system using Morse code as an adapted access communication tool. The proposed
      system includes four parts: input-control module; recognition module; wireless
      control module; and electronic-equipment-control module. The signals are
      transmitted using adopted radio frequencies, which permits long distance
      transmission without space limitation. Experimental results revealed that three
      participants with physical handicaps were able to gain access to electronic
      facilities after two months' practice with the new system.

PMID- 14960125
TI  - Drugs for stroke recovery: the example of amphetamines.
AB  - Clinical trials of pharmacological agents in stroke have mainly focused on events
      that need to be modified in the very acute stage, such as restoration of blood
      flow with thrombolytic therapy or reducing the effects of ischaemia with
      neuroprotective therapy. Thrombolytic therapy is, however, only effective within
      the first few hours of stroke onset and so far, no neuroprotective therapy has
      proven to be efficacious in humans. Thus, there is a great need for new
      pharmacological strategies to improve outcome after stroke. Accumulating evidence
      supports the assumption that the brain is plastic and improvements can be
      expected after permanent injuries. Acute and chronic alterations in
      neurotransmitter regulation after injury affects plasticity and may thus provide
      a basis for new pharmacological targets for stroke recovery. The search for
      pharmacological therapies that affect the recovery process after a permanent
      injury has been intensified during the last decade. Amphetamines, in combination
      with training, are currently one of the most promising pharmacological strategies
      studied for recovery after stroke. Several non-mutually exclusive hypotheses,
      more or less supported by experimental studies, have tried to explain the
      mechanisms underlying the facilitation of recovery of function with amphetamine
      treatment. Amphetamines are believed to hasten the processes in the brain, such
      as plasticity mechanisms and resolution of diaschisis. The combination of
      amphetamine and task-specific training seems to be of importance to the outcome.
      Results from animal studies are consistent between different models and species,
      and mainly show an increased rate of recovery but there are a few exceptions,
      with some studies reporting no effect or even a decreased recovery rate. In
      humans the number of randomised controlled studies of amphetamines is growing
      rapidly. Results from a Cochrane systematic review indicate a faster motor and
      language recovery rate with treatment, but the number of studies is too few and
      studies are too small to draw definite conclusions about the effect on recovery
      of stroke. Data in the systematic review also indicate that the mortality rate is
      higher in amphetamine-treated patients compared with placebo-treated patients.
      However, this is most likely because of baseline imbalances between the treatment
      groups with patients with more severe strokes being allocated to amphetamine
      treatment. Further clinical trials are justified, but at present amphetamines
      should not be used in clinical practice.

PMID- 14960127
TI  - Common fungal infections of the feet in patients with diabetes mellitus.
AB  - Superficial fungal infections of the foot (tinea pedis and onychomycosis) are
      common among elderly patients. Although most authorities believe that patients
      with diabetes mellitus have an increased predisposition to dermatophytic
      infections, some controversies still remain. Because these infections disrupt the
      skin integrity and provide an avenue for bacterial superinfection, elderly
      diabetic patients with dermatophytic infection should be promptly treated with an
      antifungal agent. For most dermatophytic infections of the foot, topical agents
      are usually effective and less expensive than oral agents. Laboratory diagnosis
      of fungal infection prior to institution of therapy is recommended. Proper
      technique for obtaining the specimen is important to ensure a higher chance of
      isolating the infecting fungus. Commonly used anti-dermatophytic agents that are
      also active against the yeasts include the imidazoles, the allylamines
      benzylamines and the hydroxypyridones, which are also effective against most of
      the moulds. Oral therapy for tinea pedis, although not well studied, should be
      limited to patients with more extensive infections, such as vesicobullous and
      moccasin type, resistant infections or chronic infections. In addition, oral
      agents should also be considered in diabetic and immunosuppressed patients. On
      the other hand, treatment of onychomycosis of the foot usually requires systemic
      therapy. Griseofulvin is the least effective agent when compared with the newer
      agents. Terbinafine, itraconazole and fluconazole have been shown to have
      acceptable cure rates. More recently, topical treatment of the nail with 8%
      ciclopirox nail lacquer, bifonazole with urea and amorolfine have been reported
      to be successful. Over the past decade, fungal foot infections of the skin and
      nail are more effectively treated with the introduction of numerous topical and
      oral agents.

PMID- 14960129
TI  - Spotlight on vardenafil in erectile dysfunction.
AB  - Vardenafil (Levitra) is a potent and highly selective oral phosphodiesterase type
      5 (PDE5) inhibitor. Vardenafil improved erectile function in men with mild to
      severe erectile dysfunction (ED) of varying aetiology in two randomised, double
      blind, multicentre, fixed-dose studies of 12 or 26 weeks' duration. Men receiving
      vardenafil 10 or 20mg had significantly greater improvements in International
      Index of Erectile Function (IIEF) questionnaire erectile function domain scores
      than placebo recipients. Moreover, improvements in penetration and maintenance of
      erection (assessed using IIEF or Sexual Encounter Profile [SEP] questions) were
      significantly greater with vardenafil 5-20mg than with placebo. Improvements in
      IIEF intercourse satisfaction and orgasmic function domain scores were
      significantly greater with vardenafil 10 or 20mg than with placebo and the
      proportion of patients with a positive response to a Global Assessment Question
      (GAQ) concerning improvement in erections after 12 or 26 weeks' therapy was
      significantly higher with vardenafil 5-20mg than with placebo. Vardenafil
      improved erectile function in men with ED associated with diabetes mellitus or ED
      following unilateral or bilateral nerve-sparing radical retropubic prostatectomy
      in two randomised, double-blind, multicentre, fixed-dose, 3-month studies. In
      both studies, improvements from baseline in the erectile function domain score of
      the IIEF and in positive responses to SEP questions were significantly greater
      with vardenafil 10 or 20mg than with placebo. In addition, a significantly higher
      proportion of vardenafil 10 or 20mg recipients than placebo recipients had
      positive GAQ responses. Vardenafil was generally well tolerated in men with ED;
      treatment-emergent adverse events were of mild to moderate intensity and
      transient in nature. The most commonly reported adverse events (typical of those
      seen with PDE5 inhibitors) in vardenafil 5-20mg recipients included headache,
      flushing, rhinitis, dyspepsia and sinusitis. There were no reports of abnormal
      colour vision in men with ED taking vardenafil at clinically recommended doses (5
      20mg). CONCLUSION: Vardenafil is a potent and highly selective oral PDE5
      inhibitor. It is effective and generally well tolerated in men with mild to
      severe ED of varying aetiology, as well as in men with ED associated with
      diabetes mellitus or ED after radical prostatectomy. Vardenafil should be
      considered a first-line treatment option in men with ED who are suitable
      candidates for oral PDE5 inhibitor therapy.

PMID- 14960126
TI  - Role of hydrogen peroxide in the aetiology of Alzheimer's disease: implications
      for treatment.
AB  - Hydrogen peroxide (H(2)O(2)) is a stable, uncharged and freely diffusable
      reactive oxygen species (ROS) and second messenger. The generation of H(2)O(2) in
      the brain is relatively high because of the high oxygen consumption in the
      tissue. Alzheimer's disease is a neurodegenerative disorder characterised by the
      appearance of amyloid-beta (Abeta)-containing plaques and hyperphosphorylated tau
      containing neurofibrillary tangles. The pathology of Alzheimer's disease is also
      associated with oxidative stress and H(2)O(2) is implicated in this and the
      neurotoxicity of the Abeta peptide. The ability for Abeta to generate H(2)O(2),
      and interactions of H(2)O(2) with iron and copper to generate highly toxic ROS,
      may provide a mechanism for the oxidative stress associated with Alzheimer's
      disease. The role of heavy metals in Alzheimer's disease pathology and the
      toxicity of the H(2)O(2) molecule may be closely linked. Drugs that prevent
      oxidative stress include antioxidants, modifiers of the enzymes involved in ROS
      generation and metabolism, metal chelating agents and agents that can remove the
      stimulus for ROS generation. In Alzheimer's disease the H(2)O(2) molecule must be
      considered a therapeutic target for treatment of the oxidative stress associated
      with the disease. The actions of H(2)O(2) include modifications of proteins,
      lipids and DNA, all of which are effects seen in the Alzheimer's disease brain
      and may contribute to the loss of synaptic function characteristic of the
      disease. The effectiveness of drugs to target this component of the disease
      pathology remains to be determined; however, metal chelators may provide an
      effective route and have the added bonus in the case of clioquinol of potentially
      reducing the Abeta load. Future research and development of agents that
      specifically target the H(2)O(2) molecule or enzymes involved in its metabolism
      may provide the future route to Alzheimer's disease therapy.

PMID- 14960130
TI  - Managing allegations of scientific misconduct and fraud: lessons from the "Hall
      affair".

PMID- 14960128
TI  - Management of colorectal cancer in elderly patients: focus on the cost of
      chemotherapy.
AB  - The treatment of colorectal cancer has evolved dramatically over the last 15
      years. Advances in surgery, radiotherapy and chemotherapy have enabled
      oncologists to cure more patients and offer improved quality of life to patients
      not amenable to cure. Specific knowledge of colorectal cancer care of the
      elderly, while lagging behind the treatment of younger patients, is beginning to
      emerge. Informed by recent trials, the approach towards elderly patients is
      shifting towards more aggressive treatment and multimodal therapy. Surgeons are
      operating on the elderly with greater frequency, less operative mortality and
      greater success; 5-year survival following potentially curative surgery has risen
      from 50% to 67%.Research of adjunctive therapy for colorectal cancer is enrolling
      more elderly patients, and with this has come an understanding of the role of
      chemotherapeutic agents in the treatment of the elderly, used individually and
      within multi-drug regimens. This research offers insight into how the elderly
      respond to chemotherapy, informing clinicians on anticipated benefits and
      toxicities of treatment. Fluorouracil-based regimens, which have long been the
      standard adjuvant chemotherapy, have been shown to offer benefits to the elderly
      compared with those not receiving adjuvant chemotherapy (71% versus 64% 5-year
      survival), and to cause similar toxicities as seen in younger patients. The role
      of novel chemotherapeutic agents in the treatment of elderly patients with
      colorectal cancer is also emerging, with studies finding that irinotecan, in
      combination with a fluorouracil-based regimen, can offer a further survival
      benefit of over 2 months compared with fluorouracil alone. While newer agents
      such as capecitabine, oxaliplatin, raltitrexed and tegafur/uracil (UFT) have been
      focused upon by clinical researchers, data on their use in the elderly remain
      unconvincing. Not only are we approaching a clearer understanding of the
      effectiveness of cancer care among the elderly, but research is also beginning to
      identify the cost effectiveness of both standard and emerging chemotherapeutic
      agents. Cost effectiveness of fluorouracil-based regimens, depending on delivery
      strategy, use of modulating agents and stage of cancer vary from US dollars 2000
      per quality-adjusted life-year (QALY) to US dollars 20200 per QALY (1992 values).
      Irinotecan therapy has not been fully investigated from the perspective of cost
      effectiveness; the figure of US dollars 10000 per QALY (1998 values) for
      irinotecan monotherapy over fluorouracil regimens is likely an underestimate,
      while cost analysis of irinotecan and fluorouracil combination therapy has not
      yet been reported. Our understanding of cost effectiveness of other novel agents
      has lagged behind; further research on these agents is needed. Nonetheless, as
      the effects of these novel agents upon both outcomes and costs continue to be
      defined, both curative and palliative treatment of colorectal cancer in the
      elderly patient will become more sophisticated and effective.

PMID- 14960131
TI  - Health and foreign policy: moving forward with greater focus.

PMID- 14960132
TI  - Globalisation: what is it and how does it affect health?
AB  - The term "globalisation" tends to be misused and overused. We need greater
      clarity in our understanding of the globalisation process, including the distinct
      changes involved and their relation to human health. The health impacts of
      globalisation are simultaneously positive and negative, varying according to
      factors such as geographical location, sex, age, ethnic origin, education level,
      and socioeconomic status. Globalisation is not an unstoppable force. Our key
      challenge is to create socially and environmentally sustainable forms of
      globalisation that provide the greatest benefits and least costs, shared more
      equitably than is currently the case. The health community must engage more
      directly in current research and policy debates on globalisation and encourage
      values that promote human health. At the same time, those at the helm of
      globalisation processes must recognise that attending to health impacts will
      strengthen the long-term sustainability of globalisation.

PMID- 14960133
TI  - Nailing health planks into the foreign policy platform: the Canadian experience.
AB  - Foreign policy, especially trade policy, can have dramatic but rarely considered
      effects on public health. International human rights covenants oblige governments
      to scrutinise their foreign policy, including trade policy, for its impact on the
      progressive realisation of the right to health. Health is both a means and an end
      of development policy, but government investments in health are inadequate to
      reduce health disparities within and between nations. Few donor countries provide
      the agreed target of 0.7% of gross national income for development aid or toward
      reaching the Millennium Development Goals. The progressive liberalisation
      requirement of the General Agreement on Trade in Services (GATS), if applied to
      commitments in health care, education, and water and sanitation services, may
      conflict with the progressive realisation obligation of the right to health.
      Alternatives to regulating trade in such essential services are proposed in this
      article.

PMID- 14960134
TI  - Health, human rights and Australia's foreign policies.
AB  - International human rights law affirms that everyone has a right to the enjoyment
      of the highest attainable standard of physical and mental health. States that are
      parties to human rights treaties are obliged under international law to observe
      these rights. Australia has ratified all international human rights law
      instruments in which the right to health is enshrined, and so is obliged to
      ensure that its foreign policy, including its development assistance program,
      contributes towards the progressive realisation of the right to health.
      International trade regulation should be consonant with the progressive
      realisation of the right to health globally.

PMID- 14960135
TI  - Australian engagement: workshop recommendations.

PMID- 14960136
TI  - Global health: epilogue.

PMID- 14960137
TI  - Looking beyond the national interest: reconstructing the debate on health and
      foreign policy.
AB  - Current international instability has promoted health to the foreign and security
      policy agenda; however, health is narrowly conceived in terms of promoting the
      national interest and defending the state, particularly from the risks of
      infectious disease and bioterrorism. This development involves the risk of global
      health being co-opted into an international agenda that focuses narrowly on
      security concerns rather than on broader global health issues. An alternative
      construction places greater emphasis on shared humanitarian values in a
      globalised world. This offers a more equal relationship between health and
      foreign policy and allows a broader range of issues (eg, trade in goods and
      services affecting health) to be considered in bringing together global health
      and foreign and security policy.

PMID- 14960138
TI  - Marrying foreign policy and health: feasible or doomed to fail?
AB  - Although there appears to be no Australian foreign policy statement on health,
      much of our existing foreign policy has health implications, ranging across
      security, economic, political and humanitarian objectives. Humanitarian motives
      have influenced Australia's foreign-aid policy, but our aid program, like our
      wider foreign policy, has a large national interest component. A generalised
      approach to health and foreign policy activities is difficult given the disparate
      direct and indirect links between foreign policy and global health issues, and
      the various official and unofficial interests and responsibilities involved. The
      greatest benefit may come from the health community making its own judgements on
      health priorities and seeking to engage in specific terms with foreign policy
      makers.

PMID- 14960139
TI  - "Brain drain" or ethical recruitment?
AB  - Recruitment by wealthy countries of health personnel from developing countries is
      threatening the viability of crucial health programs in poor countries,
      especially in sub-Saharan Africa. Australia has participated in this "brain
      drain", although the extent and impact of this on different countries has not
      been adequately assessed. Australia depends on overseas-trained doctors to fill
      vacancies in public hospitals and private practice, particularly in rural and
      outer suburban areas where locally trained professionals are reluctant to work.
      Australia should adopt national strategies to minimise harm and maximise benefits
      of skills migration; concerted international action will also be required.

PMID- 14960140
TI  - Lyodura use and the risk of iatrogenic Creutzfeldt-Jakob disease in Australia.
AB  - Although infectiousness is a feature of Creutzfeldt-Jakob disease (CJD), only a
      small proportion of cases are linked to transmission through healthcare
      provision. As of January 2003, over 120 cases of CJD associated with use of human
      cadaveric dura mater had been recognised worldwide; almost all were associated
      with the commercial product Lyodura. Most cases (97) have occurred in Japan,
      giving an overall risk estimate of around 1 per 2268 patients treated with
      Lyodura (0.04%) in that country. In Australia, five cases of CJD have so far been
      linked to Lyodura, but, given the protracted tails of previous epidemics of
      transmissible spongiform encephalopathies, further cases are possible. Results of
      surveys of Lyodura use in Australia are incomplete, but information from the
      manufacturer suggests that 2208-2478 sheets of Lyodura may have been used here.
      This use translates to a relatively high incidence of Lyodura-associated CJD,
      with current overall rates appearing around five times higher than those reported
      in Japan; reasons for this difference are unclear.

PMID- 14960141
TI  - Small bowel malignancy: an elusive diagnosis.

PMID- 14960142
TI  - 5: Diagnosis and management of hyperthyroidism and hypothyroidism.
AB  - The most common cause of hyperthyroidism in Australia is Graves disease, caused
      by a defect in immunoregulation in genetically predisposed individuals, leading
      to production of thyroid-stimulating antibodies. Each of the three modalities of
      therapy for Graves disease--thionamide drugs, subtotal or total thyroidectomy,
      and radioactive iodine ablation--can render the patient euthyroid, but all have
      potential adverse effects and may not eliminate recurrences. Hypothyroidism
      occurs in about 5% of the adult population; most present with "subclinical"
      hypothyroidism (mild thyroid failure), characterised by raised levels of serum
      thyroid stimulating hormone (TSH) but normal free thyroxine (T(4)). The most
      common cause of hypothyroidism in Australia is autoimmune chronic lymphocytic
      thyroiditis, characterised by raised circulating levels of thyroid peroxidase
      antibody. Symptoms and signs of hypothyroidism are often mild or subtle and, when
      there is clinical suspicion, thyroid function tests are needed; if serum TSH
      level is raised, free T(4) and thyroid peroxidase antibody should be measured.
      Replacement therapy with thyroxine is the cornerstone of therapy (1.6 microg/kg
      lean body weight daily, taken on an empty stomach); combination therapy with
      thyroxine and liothyronine (T(3)) is promoted, but there is little evidence of
      its clinical benefit. Despite the development of highly sensitive laboratory
      tests, clinical assessment and judgement remain paramount

PMID- 14960143
TI  - Occupational exposure to HIV: response to a system failure.

PMID- 14960144
TI  - Management of healthcare workers after occupational exposure to hepatitis C
      virus.

PMID- 14960145
TI  - Is grand multiparity an independent predictor of pregnancy risk? A retrospective
      observational study.

PMID- 14960146
TI  - Prevention of cardiovascular disease: an evidence-based clinical aid.

PMID- 14960147
TI  - Fatal fulminant hepatic failure induced by a natural therapy containing kava.

PMID- 14960148
TI  - Licensing thalidomide in Australia.

PMID- 14960149
TI  - Transcriptional regulation of the human TRIF (TIR domain-containing adaptor
      protein inducing interferon beta) gene.
AB  - TRIF [TIR (Toll/interleukin-1 receptor) domain-containing adaptor protein
      inducing interferon beta; also known as TICAM-1 (TIR-containing adaptor molecule
      1)] is a key adaptor for TLR3 (Toll-like receptor 3)- and TLR4-mediated
      signalling. We have performed a detailed annotation of the human TRIF gene and
      fine analysis of the basal and inducible promoter elements lying 5' to the site
      of initiation of transcription. Human TRIF maps to chromosome 19p13.3 and is
      flanked upstream by TIP47, which encodes the mannose 6-phosphate receptor binding
      protein, and downstream by a gene encoding FEM1a, a human homologue of the
      Caenorhabditis elegans Feminisation-1 gene. Using promoter-reporter deletion
      constructs, we identified a distal region with the ability to negatively regulate
      basal transcription and a proximal region containing an Sp1 (stimulating protein
      1) site that confers approx. 75% of basal transcriptional activity. TRIF
      expression can be induced by multiple stimuli, such as the ligands for TLR2, TLR3
      and TLR4, and by the pro-inflammatory cytokines tumour necrosis factor alpha and
      interleukin-1alpha. All of these stimuli act via an NF-kappaB (nuclear factor
      kappaB) motif at position -127. In spite of the presence of a STAT1 (signal
      transduction and activators of transcription 1) motif at position -330, the
      addition of type I or type II interferon had no effect on TRIF activity. The
      human TRIF gene would therefore appear to be regulated primarily by NF-kappaB.

PMID- 14960150
TI  - Partial reconstruction of in vitro gluconeogenesis arising from mitochondrial l
      lactate uptake/metabolism and oxaloacetate export via novel L-lactate
      translocators.
AB  - In the light of the occurrence of L-lactate dehydrogenase inside the
      mitochondrial matrix, we looked at whether isolated rat liver mitochondria can
      take up and metabolize L-lactate, and provide oxaloacetate outside mitochondria,
      thus contributing to a partial reconstruction of gluconeogenesis in vitro. We
      found that: (1) L-lactate (10 mM), added to mitochondria in the presence of a
      cocktail of glycolysis/gluconeogenesis enzymes and cofactors, can lead to
      synthesis of glyceraldehyde-3-phosphate at a rate of about 7 nmol/min per mg
      mitochondrial protein. (2) Three novel translocators exist to mediate L-lactate
      traffic across the inner mitochondrial membrane. An L-lactate/H+ symporter was
      identified by measuring fluorimetrically the rate of endogenous pyridine
      nucleotide reduction. Consistently, L-lactate oxidation was found to occur with
      P/O ratio=3 (where P/O ratio is the ratio of mol of ATP synthesized to mol of
      oxygen atoms reduced to water during oxidative phosphorylation) and with
      generation of membrane potential. Proton uptake, which occurred as a result of
      addition of L-lactate to RLM together with electron flow inhibitors, and
      mitochondrial swelling in ammonium L-lactate solutions were also monitored. L
      Lactate/oxaloacetate and L-lactate/pyruvate anti-porters were identified by
      monitoring photometrically the appearance of L-lactate counter-anions outside
      mitochondria. These L-lactate translocators, which are distinct from the
      monocarboxylate carrier, were found to differ from each other in V(max) values
      and in inhibition and pH profiles, and proved to regulate mitochondrial L-lactate
      metabolism in vitro. The role of lactate/mitochondria interactions in
      gluconeogenesis is discussed.

PMID- 14960151
TI  - Transcription factor Nrf2/MafK regulates rat placental glutathione S-transferase
      gene during hepatocarcinogenesis.
AB  - The rat GST-P (placental glutathione S-transferase), a phase II detoxifying
      enzyme, is not expressed in normal liver cells, but is highly and specifically
      induced during early hepatocarcinogenesis as well as in hepatocellular carcinoma
      cells. Results of previous studies indicated that GST-P gene activation was
      mainly controlled by an enhancer element, GPE1 (GST-P enhancer 1), but the
      specific activation mechanism of the GST-P gene was not fully understood
      [Morimura, Suzuki, Hochi, Yuki, Nomura, Kitagawa, Nagatsu, Imagawa and Muramatsu
      (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 2065-2068; Suzuki, Imagawa, Hirabayashi,
      Yuki, Hisatake, Nomura, Kitagawa and Muramatsu (1995) Cancer Res. 55, 2651-2655].
      In the present study, we investigate the transcription factor Nrf2/MafK
      heterodimer (where Nrf2 stands for NF-E2 p45-related factor 2) as an activator of
      the GST-P gene through the action of GPE1 during hepatocarcinogenesis.
      Electrophoretic mobility-shift assay and footprinting analysis with wild-type
      GPE1 and GPE1 point mutants showed that the Nrf2/MafK heterodimer specifically
      bound GPE1. Reporter transfection assays indicated that Nrf2 strongly stimulated
      GST-P gene expression in mouse F9 embryonal carcinoma cells and H4IIE rat
      hepatoma cells. Northern-blot analysis indicated that GST-P and Nrf2 mRNA
      increased in parallel with development of precancerous lesions and hepatocellular
      carcinoma. Keap1 (Kelch-like ECH-associated protein 1), an inhibitory factor of
      Nrf2, decreased the activation of GPE1 by Nrf2 and this suppression was restored
      after treatment with electrophilic compounds. GST-P mRNA expression in H4IIE
      cells was induced by electrophilic compounds, as was the expression of mRNAs of
      other phase II detoxifying enzymes. Chromatin immunoprecipitation analyses showed
      that antibodies both against Nrf2 and against MafK precipitated GPE1 from the
      chromatin of the pre-neoplastic hepatocytes and rat hepatoma cells (H4IIE and
      dRLh84), but not from normal hepatocytes. These results indicate that the
      Nrf2/MafK heterodimer regulates GST-P gene expression during early
      hepatocarcinogenesis and in hepatoma cells.

PMID- 14960153
TI  - Preface.

PMID- 14960152
TI  - Iron-regulatory proteins DmdR1 and DmdR2 of Streptomyces coelicolor form two
      different DNA-protein complexes with iron boxes.
AB  - In high G+C Gram-positive bacteria, the control of expression of genes involved
      in iron metabolism is exerted by a DmdR [divalent (bivalent) metal-dependent
      regulatory protein] in the presence of Fe2+ or other bivalent ions. The dmdR1 and
      dmdR2 genes of Streptomyces coelicolor were overexpressed in Escherichia coli and
      the DmdR1 and DmdR2 proteins were purified to homogeneity. Electrophoretic
      mobility-shift assays showed that both DmdR1 and DmdR2 bind to the 19-nt tox and
      desA iron boxes forming two different complexes in each case. Increasing the
      concentrations of DmdR1 or DmdR2 protein shifted these complexes from their low
      molecular-mass form to the high-molecular-mass complexes. Formation of the DNA
      protein complexes was prevented by the bivalent metal chelating agent 2,2'
      dipyridyl and by antibodies specific against the DmdR proteins. Cross-linking
      with glutaraldehyde of pure DmdR1 or DmdR2 proteins showed that DmdR1 forms
      dimers, whereas DmdR2 is capable of forming dimers and probably tetramers. Ten
      different iron boxes were found in a search for iron boxes in the genome of S.
      coelicolor. Most of them correspond to putative genes involved in siderophore
      biosynthesis. Since the nucleotide sequence of these ten boxes is identical (or
      slightly different) with the synthetic DNA fragment containing the desA box used
      in the present study, it is proposed that DmdR1 and DmdR2 bind to the iron boxes
      upstream of at least ten different genes in S. coelicolor.

PMID- 14960154
TI  - Karl Wilhelm Kupffer And His Contributions To Modern Hepatology.

PMID- 14960155
TI  - Molecular mechanism of stellate cell activation and therapeutic strategy for
      liver fibrosis.

PMID- 14960156
TI  - 3-D structure of extracellular matrix regulates gene expression in cultured
      hepatic stellate cells to induce process elongation.
AB  - HSCs showed myofibroblast-like shapes when cultured on polystyrene surface or on
      type I collagen-coated surface, whereas HSCs cultured on type I collagen gel were
      induced to elongate cellular processes, suggesting that HSCs recognize 3-D
      structure of extracellular type I collagen fibrils and change their morphology
      and function. In this study we examined the differentially regulated gene
      expression by extracellular matrix (ECM) components by PCR-differential display
      (PCR-DD) analysis followed by cloning and FASTA homology search, and identified
      the mRNA species as a transcription factor SP1, breast cancer resistant protein
      (BCRP), dystonin, and KAP3B. Regulation of dystonin and KAP3B expression was
      confirmed by RT-PCR analysis. Thus, cell surface-binding to extracellular
      interstitial collagen may trigger intracellular signaling and alteration in gene
      expression, and HSCs not only produce various ECM components but also change
      their morphology and gene expression in response to ECM components adhering to
      the cells.

PMID- 14960157
TI  - Signals for Hepatic Figrogenesis in Pediatric Cholestatic Liver Disease: Review
      and Hypothesis.

PMID- 14960158
TI  - Thioredoxin prevents thioacetamide-induced acute hepatitis.

PMID- 14960159
TI  - PPAR Gamma and Hepatic Stellate Cells.
AB  - Activation of Hepatic stellate cells (HSC) in fibrogenesis involves distinct
      morphological and biochemical changes. This activation requires the coordinated
      changes in activity of several transcription factors. Peroxisome proliferator
      activated receptor gamma (PPAR gamma) is one such factor whose activity is
      decreased in activated HSC. PPAR gamma ligands suppress several markers of HSC
      activation such as expression of collagen and alpha smooth muscle actin (alpha
      SMA), cell proliferation and migration. Expression of PPAR gamma, per se, also
      inhibits HSC activation. These findings support the role of PPAR gamma in
      reversion of activated HSC toward their quiescent state.

PMID- 14960160
TI  - N-Cadherin cleavage during activated hepatic stellate cell apoptosis is inhibited
      by tissue inhibitor of metalloproteinase-1.
AB  - Apoptosis of hepatic stellate cells (HSC) has previously been shown to occur
      during spontaneous resolution of experimental liver fibrosis. TIMP-1 has also
      been shown to have a key role because of its ability to inhibit apoptosis of HSC
      via matrix metalloproteinase (MMP) inhibition. This has led to further study of
      novel substrates for MMPs that might impact on HSC survival. N-Cadherin is known
      to mediate cell-cell contacts in fibroblasts. In this study we demonstrate that N
      Cadherin is expressed by activated rat HSC. Furthermore, during apoptosis of HSC,
      the N-Cadherin is cleaved into smaller fragments. Apoptosis of HSC may be
      inhibited by TIMP-1. This is associated with reduced fragmentation of N-Cadherin.
      N-Cadherin may have an important role in supporting HSC survival while N-Cadherin
      cleavage may play a part in promoting HSC apoptosis in recovery from liver
      fibrosis.

PMID- 14960161
TI  - Amino acids, L-Cysteine and L-Methionine, Attenuate Activation of Rat Stellate
      Cells in Primary Culture.

PMID- 14960162
TI  - Involvement of Galectin-1 and Galectin-3 in Proliferation and Migration of Rat
      Hepatic Stellate Cells in Culture.

PMID- 14960163
TI  - Suppression of Rat Stellate Cell Activation and Liver Fibrosis by a Japanese
      Herbal Medicine, Inchinko-to (TJ135).

PMID- 14960164
TI  - Expression of leptin receptors in hepatic sinusoidal cells.
AB  - Emerging evidence has suggested a critical role of leptin in hepatic inflammation
      and fibrogenesis, however, the precise mechanisms underlying the profibrogenic
      action of leptin in the liver has not been well elucidated. Therefore, the
      present study was designed to investigate the expression and functions of leptin
      receptors (Ob-R) in hepatic sinusoidal cells. Hepatic stellate cells (HSCs),
      Kupffer cells and sinusoidal endothelial cells (SECs) were isolated from rat
      livers by in situ collagenase perfusion followed by differential centrifugation
      technique, and expression of Ob-Ra and Ob-Rb, short and long Ob-R isoforms,
      respectively, were analyzed by RT-PCR. Ob-Ra mRNA was detected ubiquitously in
      HSCs and SECs. In contrast, Ob-Rb was detected clearly only in SECs and Kupffer
      cells, but not in 7-day cultured HSCs. Indeed, tyrosine-phosphorylation of STAT
      3, a downstream event of Ob-Rb signaling, was observed in SECs, but not in HSCs,
      1 hr after incubation with leptin. Further, leptin increased AP-1 DNA binding
      activity and TGF-beta 1 mRNA levels in Kupffer cells and SECs, whereas leptin
      failed to increase TGF-beta 1 mRNA in HSCs. These findings indicated that SECs
      and Kupffer cells, but not HSCs, express functional leptin receptors, through
      which leptin elicits production of TGF-beta 1. It is hypothesized therefore that
      leptin, produced systemically from adipocytes and locally from HSCs, up-regulates
      TGF-beta 1 thereby facilitate tissue repairing and fibrogenesis in the sinusoidal
      microenvironment.

PMID- 14960165
TI  - Intercellular Adhesive Structures Between Stellate Cells - An Analysis in
      Cultured Human Hepatic Stellate Cells.
AB  - To investigate whether or not hepatic stellate cells can form intercellular
      junctions with each other, we cultured human stellate cells (LI90) on different
      kinds of substrata. Intercellular junctions were detected between these cultured
      stellate cells by transmission electron microscopy (TEM). The molecular
      components of the intercellular adhesive structures were identified by
      immunofluorescence microscopy. Immunofluorescence for cadherin and catenins was
      detected at the adhesion sites between the cultured stellate cells. Thus, the
      intercellular junctions were indicated to be adherens junctions at the molecular
      level. The junctions developed in the cultured stellate cells irrespective of the
      type of substratum. These data suggest that the junctional formation between the
      stellate cells occurs in vivo as well as in vitro.

PMID- 14960166
TI  - Activation of Stellate Cells Before Induction of Hepatic Fibrosis - Precise
      Timing in Choline-deficient Diet-fed Rat Model.

PMID- 14960167
TI  - Periportal Stellate Cells in Subjects with Chronic Hepatitis C with a Varied
      Serum Alanine Aminotransferase Level.

PMID- 14960168
TI  - Intralobular Distribution of Vitamin A-Storing Lipid Droplets in Hepatic Stellate
      Cells with Special Reference to Polar Bear and Arctic Fox.
AB  - We examined the liver of adult polar bears, arctic foxes, and rats by gold
      chloride staining, fluorescence microscopy for the detection of autofluorescence
      of vitamin A, hematoxylin-eosin staining, staining with Masson's trichrome, Ishii
      and Ishii's silver impregnation, and transmission electron microscopical
      morphometry. The liver lobules of the arctic animals showed a zonal gradient in
      the storage of vitamin A. The density (i.e., cell number per area) of hepatic
      stellate cells was essentially the same among the zones. These results indicate
      that the hepatic stellate cells of the polar bears and arctic foxes possess
      heterogeneity of vitamin A-storing capacity in their liver lobules.

PMID- 14960169
TI  - Expression of the Peroxisome Proliferator-Activated Receptors (PPARs) in the
      Hepatic Stellate Cells.

PMID- 14960170
TI  - Decreased Capacity for Vitamin A Storage in Hepatic Stellate Cells for Arctic
      Animals.

PMID- 14960171
TI  - 5-Lipoxygenase (5-LO) is Involved in Kupffer Cell Survival. Possible Role of 5-LO
      Products in the Pathogenesis of Liver Fibrosis.

PMID- 14960172
TI  - Regulation of matrix metallo-proteinase expression by extracellular matrix
      components in cultured hepatic stellate cells.
AB  - Hepatic stellate cells (HSC) changed their morphology and function including
      production of matrix metalloproteinases (MMPs) in response to extracellular
      matrix (ECM) component used as a substratum in culture. We examined in this study
      the regulatory role of ECM component on expression of MMPs and tissue inhibitor
      of metalloproteinase (TIMP) in rat HSCs cultured on polystyrene, type I collagen
      coated surface, type I collagen gel, or Matrigel, respectively. When cultured on
      type I collagen gel, HSCs showed the asteroid cell shape and MMP-1 activity, as
      detected by in situ zymography. Expression of MMP-1 protein and mRNA were
      examined by using immunofluorescence staining and RT-PCR analysis in HSCs
      cultured on type I collagen gel. Active form of MMP-2 was detected by gelatin
      zymography in the conditioned medium of HSCs cultured on type I collagen gel,
      whereas it was not detected when HSCs were cultured on polystyrene, type I
      collagen-coated surface, or Matrigel. Increased MMP-2 mRNA was detected by RT-PCR
      in HSCs cultured on type I collagen gel. Increased MT1-MMP proteins were shown to
      localize on the cell membrane by using immunofluorescence staining in HSCs
      cultured on type I collagen gel. Elevated expression of membrane-type matrix
      metallproteinase-1 (MT1-MMP) mRNA and tissue inhibitor of metalloproteinase-2
      (TIMP-2) mRNA was detected by RT-PCR in HSCs cultured on type I collagen-coated
      surface or type I collagen gel. These results indicate that expression of MMPs
      and TIMP-2 is regulated by ECM components in cultured HSCs, suggesting an
      important role of HSCs in the remodeling of liver tissue.

PMID- 14960173
TI  - HMG-COA reductase inhibitor modulates collagen GEL-contraction by hepatic
      myofibroblast-like stellate cell line: involvement of geranylgeranylated
      proteins.

PMID- 14960174
TI  - Clearance function of scavenger endothelial cells.

PMID- 14960175
TI  - Fc Gamma Receptors in the Hepatic Sinusoid.

PMID- 14960176
TI  - The liver sinusoidal endothelial cell hyaluronan receptor and its homolog,
      stabilin-1 - Their roles (known and unknown) in endocytosis.

PMID- 14960177
TI  - Malondialdehyde-acetaldehyde (MAA) modified proteins induce pro-inflammatory and
      pro-fibrotic responses by liver endothelial cells.

PMID- 14960178
TI  - Preliminary analysis of the sinusoidal endothelium and space of Disse in ageing
      Papio hamadrayas.

PMID- 14960179
TI  - The effect of cytochalasin B - Loaded liposomes on the ultrastructure of the
      liver sieve.

PMID- 14960180
TI  - Study of the reappearance of sieve plate-like pores in immortalized sinusoidal
      endothelial cells - Effect of actin inhibitor in mixed perfusion cultures.

PMID- 14960181
TI  - Role of Hepatic Stellate Cells in the Early Phase of Liver Regeneration in Rat:
      Formation of Tight Adhesion to Parenchymal Cells.
AB  - We investigated activation mechanisms of hepatic stellate cells (HSCs) that are
      known to play pivotal roles in the regeneration process after 70% partial
      hepatectomy (PHx). Parenchymal liver cells (PLCs) and non-parenchymal cells
      (NPLCs) were isolated and purified from the regenerating livers at 1, 3, 7, 14
      days after PHx. Each liver cell fraction was stained by immunocytochemistry using
      an anti-desmin antibody as a marker for HSCs, anti-alpha-smooth muscle actin
      (alpha-SMA) as a marker for activated HSCs, and 5-bromo-2'-deoxyuridine (BrdU)
      for detection of proliferating cells. Tissue sections from regenerating livers
      were also analyzed by immunohistochemistry and compared with the results obtained
      for isolated cell fractions. One and 3 days after PHx, PLC-enriched fraction
      contained HSCs adhered to PLCs. The HSCs adhered to PLCs were double positive for
      BrdU and alpha-SMA, and formed clusters suggesting that these HSCs were
      activated. However, HSC-enriched fraction contained HSCs not adhered PLCs showed
      positive staining for anti-desmin antibody but negative for anti-alpha-SMA
      antibody. These results suggest that HSCs are activated by adhering to PLCs
      during the early phase of hepatic regeneration.

PMID- 14960182
TI  - Imaging Liver Development/Remodeling in the See-Through Medaka Fish.

PMID- 14960183
TI  - Lipopolysaccharide-mediated signal transduction: Stabilization of TNF-alpha mRNA
      contributes to increased lipopolysaccharide-stimulated TNF-alpha production by
      Kupffer cells after chronic ethanol feeding.

PMID- 14960184
TI  - Immunomodulatory Role of Kupffer Cell in Liver Allografts.

PMID- 14960185
TI  - Effects of acetaminophen on hepatic microcirculation in mice.

PMID- 14960186
TI  - Functional Differences between Periportal and Perivenous Kupffer Cells Isolated
      by Digitonin-Collagenase Perfusion.

PMID- 14960187
TI  - The regulatory role of prostaglandin E2 in liver (patho) physiology is controlled
      at its site of synthesis and its action on the receptors.

PMID- 14960188
TI  - Signaling role of iron in NF-kappa B activation in hepatic macrophages.
AB  - Iron is both essential and toxic for cells and impaired iron homeostasis has been
      shown to cause or potentiate various forms of liver injury. Research in our
      laboratory suggests that iron also plays a pivotal role in intracellular
      signaling for NF-kappa B activation in hepatic macrophages (HM). Our results
      showed: 1) HM from alcohol-fed rats had a increase in the nonheme iron content
      accompanied by NF-kappa B activation; 2) iron chelation normalized nonheme iron
      concentration and blocked enhanced NF-kappa B activation and TNF-alpha expression
      in these cells; 3) LPS-induced NF-kappa B activation was also blocked by iron
      chelator; 4) iron directly induced TNF-alpha expression via IKK and NF-kappa B
      activation in normal HM. We propose that iron acts as an independent
      proinflammatory molecule via induction of the intracellular signaling for NF
      kappa B activation in HM and primes the liver for chronic inflammation and
      injury.

PMID- 14960189
TI  - Thalidomide Prevents Alcoholic Liver Injury in Rats Through Inhibition of Kupffer
      Cell Sensitization.

PMID- 14960190
TI  - An in vivo Method for Determination of Endosomal Distribution of Both Ligand and
      Asialoglycoprotein Receptor in Rat Liver.

PMID- 14960191
TI  - Ultrastructural characterization of the death process of hepatocytes in neonatal
      mouse liver.

PMID- 14960192
TI  - Use of Flow Cytometric Analysis to Examine the Uptake of Apoptotic Bodies by
      Healthy Hepatocytes.

PMID- 14960193
TI  - Chemiluminescence detection of reactive oxygen species in isolated Kupffer cells
      during phagocytosis of Treponema pallidum.

PMID- 14960194
TI  - Heme oxygenase-1 induction in hepatocytes and non-parenchymal cells protects
      against liver injury during endotoxemia.
AB  - INTRODUCTION: Heme oxygenase-1 (HO-1) is a stress response enzyme, which
      catalyses the breakdown of heme into biliverdin-IX alpha, carbon monoxide and
      ferrous iron. Under situations of oxidative stress, heat stress,
      ischemia/reperfusion injury or endotoxemia, HO-1 has been shown to be induced and
      to elicit a protective effect. The mechanism of how this protective effect is
      executed is unknown. RESULTS: HO-1 induction with cobalt protoporphorin (Co-PP)
      dose-dependently protected against apoptotic cell death as well as neutrophil
      mediated oncosis in the galactosamine/endotoxin (Gal/ET) shock model. Induction
      of HO-1 with Co-PP dose-dependently protected against neutrophil-mediated oncosis
      as indicated by attenuated ALT release and TNF-mediated apoptotic cell death as
      indicated by reduced caspase-3 activation. HO-1 induction did not attenuate
      Gal/ET-induced TNF-alpha formation. Furthermore, a similar protective effect with
      the high dose of Co-PP was observed when animals were treated with Gal/TNF-alpha.
      CONCLUSIONS: HO-1 induction attenuates apoptosis and neutrophil-mediated oncosis
      in the Gal/ET shock model. However, the protective effect is not due to the
      reduction of TNF-alpha release or the attenuation of neutrophil accumulation in
      the liver sinusoids.

PMID- 14960195
TI  - Beta2-glycoprotein I inhibition of mouse Kupffer cells respiratory burst depends
      on liver architecture.

PMID- 14960196
TI  - Role of AIM in Corynebacterium-induced granuloma formation in mice.

PMID- 14960197
TI  - Precision-cut liver slices in culture as a tool to assess the physiological
      involvement of Kupffer cells in hepatic metabolism.

PMID- 14960198
TI  - Peroxynitrite formation and sinusoidal endothelial cell injury during
      acetaminophen-induced hepatotoxicity in mice.
AB  - INTRODUCTION: Vascular injury and accumulation of red blood cells in the space of
      Disse (hemorrhage) is a characteristic feature of acetaminophen hepatotoxicity.
      However, the mechanism of nonparenchymal cell injury is unclear. Therefore, the
      objective was to investigate if either Kupffer cells or intracellular events in
      endothelial cells are responsible for the cell damage. RESULTS: Acetaminophen
      treatment (300 mg/kg) caused vascular nitrotyrosine staining within 1 h. Vascular
      injury (hemorrhage) occurred between 2 and 4 h. This paralleled the time course
      of parenchymal cell injury as shown by the increase in plasma alanine
      aminotransferase activities. Inactivation of Kupffer cells by gadolinium chloride
      (10 mg/kg) had no significant effect on vascular nitrotyrosine staining,
      hemorrhage or parenchymal cell injury. In contrast, treatment with allopurinol
      (100 mg/kg), which prevented mitochondrial injury in hepatocytes, strongly
      attenuated vascular nitrotyrosine staining and injury. CONCLUSIONS: Our data do
      not support the hypothesis that acetaminophen-induced superoxide release leading
      to vascular peroxynitrite formation and endothelial cell injury is caused by
      activated Kupffer cells. In contrast, the protective effect of allopurinol
      treatment suggests that, similar to the mechanism in parenchymal cells,
      mitochondrial oxidant stress and peroxynitrite formation in sinusoidal
      endothelial cells may be critical for vascular injury after acetaminophen
      overdose.

PMID- 14960199
TI  - Kupffer and stellate cell proteoglycans mediate malaria sporozoite targeting to
      the liver.

PMID- 14960200
TI  - Chlorotyrosine protein adducts are reliable biomarkers of neutrophil-induced
      cytotoxicity in vivo.
AB  - INTRODUCTION: A limitation for investigating the pathophysiological role of
      neutrophils in vivo is the lack of a reliable biomarker for neutrophil
      cytotoxicity in the liver. Therefore, we investigated if immunohistochemical
      detection of chlorotyrosine protein adducts can be used as a specific footprint
      for generation of neutrophil-derived hypochlorous acid in vivo. METHODS:
      C3Heb/FeJ mice were treated with 100 micrograms/kg endotoxin (ET) alone or in
      combination with 700 mg/kg galactosamine (Gal/ET). Some animals received
      additionally two doses of 10 mg/kg of the pancaspase inhibitor Z-VAD-fmk. An
      antibody against chlorotyrosine was used for the immunohistochemical analysis.
      RESULTS: At 6 h after Gal/ET, hepatocellular apoptosis was evident without
      increase in plasma ALT activities. Neutrophils accumulated in sinusoids but there
      was no evidence for chlorotyrosine staining. At 7 h after Gal/ET, about 54% of
      the sequestered neutrophils had extravasated, there was extensive necrosis and
      increased plasma ALT activities. Extensive immunostaining for chlorotyrosine,
      mainly colocalized with neutrophils, could be observed. Treatment with Z-VAD-fmk
      eliminated apoptosis, necrosis and the increase in plasma ALT values. Neutrophil
      extravasation was prevented but the overall number of neutrophils in the liver
      was unchanged. Chlorotyrosine staining was absent in these samples. After ET
      alone (7 h), sinusoidal neutrophil accumulation was similar to Gal/ET treatment
      but there was no apoptosis, neutrophil extravasation, ALT release or
      chlorotyrosine staining. CONCLUSIONS: Chlorotyrosine staining in liver samples
      correlated well with evidence of neutrophil-induced liver injury in the
      endotoxemia model. These results indicate that assessment of chlorotyrosine
      protein adduct formation by immunohistochemistry could be a useful marker of
      neutrophil-induced liver cell injury in vivo.

PMID- 14960201
TI  - Cytotoxic reactions of CC531s towards liver sinusoidal endothelial cells: a
      microscopical study.

PMID- 14960202
TI  - Confocal laser scanning microscopic study of the killing of metastatic colon
      carcinoma cells by Kupffer cells in the early onset of hepatic metastasis.

PMID- 14960203
TI  - Elevated levels of tissue inhibitor of metalloproteinases (TIMPS) in human
      hepatocellular carcinomas.

PMID- 14960204
TI  - Expression of growth factors in colorectal carcinoma liver metastatic patients
      after partial hepatectomy: implications for a functional role in cell
      proliferation during liver regeneration.

PMID- 14960205
TI  - Migration of liver sinusoidal leukocytes to the liver colon adenocarcinoma
      metastases.

PMID- 14960206
TI  - Reduction of liver metastases outgrowth by tumour antigen-pulsed dendritic cell
      vaccination.

PMID- 14960207
TI  - Correlation Between in Vivo Accumulation and in Vitro Adhesion of Liver
      associated Lymphocytes in and Around Liver Adenocarcinoma Metastases.

PMID- 14960208
TI  - Histopathological characterization of hepatocellular carcinomas which are
      undetected by dynamic computed tomography.

PMID- 14960209
TI  - Expression of fibrillin-1 in focal nodular hyperplasia of the liver: a role in
      microcirculation adaptability.
AB  - INTRODUCTION: It has been suggested that the elastic network plays an important
      role in the tissue response to mechanical stress. The components of the elastic
      network have been poorly studied in liver diseases. Therefore, in this work, the
      expression and distribution of fibrillin-1 and elastin were studied in hepatic
      focal nodular hyperplasia and compared with surrounding liver and hepatocellular
      adenoma. METHODS: Immunohistochemical studies for fibrillin-1 and elastin were
      performed on unfixed cryostat sections of focal nodular hyperplasia (22 cases),
      hepatocellular adenoma (15 cases) and surrounding liver (34 cases). RESULTS:
      Surrounding normal liver showed only a continuous, thin and regular
      immunostaining of fibrillin-1 in the space of Disse, whereas elastin was nearly
      absent. In focal nodular hyperplasia, fibrillin-1 was more strongly expressed in
      the perisinusoidal space, compared with surrounding liver; in contrast, in
      adenomas fibrillin-1 immunostaining was irregular and very low in perisinusoidal
      space, more intense in peliotic areas. CONCLUSIONS: In focal nodular hyperplasia,
      the increased microfibrillar network containing fibrillin-1 in the space of Disse
      could reflect an adaptation of the sinusoidal wall to an increased arterial blood
      flow in sinusoids. In hepatocellular adenoma, the different patterns of fibrillin
      1 could be related to the heterogeneity of the arterial vascularization and to
      the frequent necrotico-hemorrhagic changes. This study comparing the elastic
      network in two types of lesions with vascularization abnormalities and in the
      surrounding liver provides interesting new data for understanding the structural
      role of fibrillin-1 in the space of Disse.

PMID- 14960210
TI  - Pit cells exclusively kill P815 tumor cells by the perforin/granzyme pathway.

PMID- 14960212
TI  - Defining diagnosis: screening and decision making in primary care.

PMID- 14960213
TI  - The potential and limitations of personalised medicine in primary care.

PMID- 14960214
TI  - Diagnosis of somatisation: effect of an educational intervention in a cluster
      randomised controlled trial.
AB  - BACKGROUND: Somatisation is highly prevalent in primary care (present in 25% of
      visiting patients) but often goes unrecognised. Non-recognition may lead to
      ineffective treatment, risk of iatrogenic harm, and excessive use of healthcare
      services. AIM: To examine the effect of training on diagnosis of somatisation in
      routine clinical practice by general practitioners (GPs). DESIGN OF STUDY:
      Cluster randomised controlled trial, with practices as the randomisation unit.
      SETTING: Twenty-seven general practices (with a total of 43 GPs) in Vejle County,
      Denmark. METHOD: Intervention consisted of a multifaceted training programme (the
      TERM [The Extended Reattribution and Management] model). Patients were enrolled
      consecutively over a period of 13 working days. Psychiatric morbidity was
      assessed by means of a screening questionnaire. GPs categorised their diagnoses
      in another questionnaire. The primary outcome was GP diagnosis of somatisation
      and agreement with the screening questionnaire. RESULTS: GPs diagnosed
      somatisation less frequently than had previously been observed, but there was
      substantial variation between GPs. The difference between groups in the number of
      diagnoses of somatisation failed to reach the 5% significance (P = 0.094).
      However, the rate of diagnoses of medically unexplained physical symptoms was
      twice as high in the intervention group as in the control group (7.7% and 3.9%,
      respectively, P = 0.007). Examination of the agreement between GPs' diagnoses and
      the screening questionnaire revealed no significant difference between groups.
      CONCLUSION: Brief training increased GPs' awareness of medically unexplained
      physical symptoms. Diagnostic accuracy according to a screening questionnaire
      remained unaffected but was difficult to evaluate, as there is no agreement on a
      gold standard for somatisation in general practice.

PMID- 14960215
TI  - Psychological treatment for insomnia in the management of long-term hypnotic drug
      use: a pragmatic randomised controlled trial.
AB  - OBJECTIVE: To evaluate the clinical and cost impact of providing cognitive
      behaviour therapy (CBT) for insomnia (comprising sleep hygiene, stimulus control,
      relaxation and cognitive therapy components) to long-term hypnotic drug users in
      general practice. DESIGN: A pragmatic randomised controlled trial with two
      treatment arms (a CBT treated 'sleep clinic' group, and a 'no additional
      treatment' control group), with post-treatment assessments commencing at 3 and 6
      months. SETTING: Twenty-three general practices in Sheffield, UK. PARTICIPANTS:
      Two hundred and nine serially referred patients aged 31-92 years with chronic
      sleep problems who had been using hypnotic drugs for at least 1 month (mean
      duration = 13.4 years). RESULTS: At 3- and 6-month follow-ups patients treated
      with CBT reported significant reductions in sleep latency, significant
      improvements in sleep efficiency, and significant reductions in the frequency of
      hypnotic drug use (all P<0.01). Among CBT treated patients SF-36 scores showed
      significant improvements in vitality at 3 months (P<0.01). Older age presented no
      barrier to successful treatment outcomes. The total cost of service provision was
      154.40 per patient, with a mean incremental cost per quality-adjusted life-year
      of  3416 (at 6 months). However, there was evidence of longer term cost offsets
      owing to reductions in sleeping tablet use and reduced utilisation of primary
      care services. CONCLUSIONS: In routine general practice settings, psychological
      treatments for insomnia can improve sleep quality and reduce hypnotic consumption
      at a favourable cost among long-term hypnotic users with chronic sleep
      difficulties.

PMID- 14960216
TI  - The quality of record keeping in primary care: a comparison of computerised,
      paper and hybrid systems.
AB  - BACKGROUND: Computerised record keeping in primary care is increasing. However,
      no study has systematically examined the completeness of computer records in
      practices using different forms of record keeping. AIM: To compare computer-only
      record keeping to paper-only and hybrid systems, by measuring the number of
      consultations and symptoms recorded within individual consultations. DESIGN OF
      STUDY: Retrospective cohort study. SETTING: Eighteen general practices in the
      Exeter Primary Care Trust. METHOD: This study was part of a retrospective case
      control study of cancer patients aged over 40 years. All recorded consultations
      for a 2-year period were identified and coded for 1396 patients. Records were
      classified as paper, computer, or hybrid, depending on which medium stored the
      clinical information from consultations. RESULTS: More consultations were
      recorded in hybrid systems (median in 2 years = 11, interquartile range [IQR] = 6
      18) than computer systems (median in 2 years = 9, IQR = 4-16.5) or paper systems
      (median in 2 years = 8, IQR = 5-14,): P <0.001. In a Poisson regression analysis,
      which included age, sex, and future cancer diagnosis, the rates of consultations
      recorded in paper and computer systems were 16% and 11% lower, respectively, than
      in hybrid systems. Fewer telephone consultations were recorded in paper systems,
      and fewer home visits in computer systems. Fewer symptoms were recorded in
      individual consultations on computer systems. Recording of absent symptoms and
      severity of symptoms was highest in paper systems. CONCLUSION: Hybrid systems of
      primary care record keeping document higher numbers of consultations than
      computer-only or paper-only systems. The quality of individual consultation
      recording is highest in paper-only systems. This has medicolegal implications and
      may impact upon continuity of care.

PMID- 14960217
TI  - Multifaceted support to improve preventive cardiovascular care: a nationwide,
      controlled trial in general practice.
AB  - BACKGROUND: Multifaceted interventions improve the quality of preventive
      cardiovascular care in general practice when applied in small-scale research
      trials. AIM: To test the transferability of observations from research trials on
      preventive cardiovascular care to a real-world situation and, therefore, evaluate
      the effectiveness of a nationwide project with a large number of practices. The
      intervention comprised a combination of conferences, dissemination of manuals,
      and support from trained non-physicians during outreach visits. DESIGN OF STUDY:
      A controlled before-and-after trial with two arms: multifaceted support versus no
      special attention. Analysis after 2 years. SETTING: 617 general practices in The
      Netherlands. METHOD: Outcomes measures were the compliance rates for 15
      indicators. Structure-of-care indicators included the use of reminders, specific
      computer files, written protocols, and special clinics. Process-of-care
      indicators included the assessment of modifiable risk factors and use of a
      minimal contact intervention (MCI) for smoking cessation. Compliance of general
      practitioners (GPs) was assessed using self-administered questionnaires. RESULTS:
      The intervention group improved on all eight of the structure-of-care indicators
      when compared to the control group. A positive effect was also found on the
      extent to which the GPs measured blood pressure in 60-year-old patients and on
      the use of an MCI for smoking cessation. No effect was found on the completeness
      of the risk-factor profiles that the GPs assessed in specific groups of high-risk
      patients. CONCLUSION: The nationwide intervention appeared to improve certain
      aspects of preventive cardiovascular care. Nevertheless, the National Association
      of GPs decided to stop the project. This decision was made within the context of
      discussions about the heavy workloads and insufficient incomes being experienced
      by GPs.

PMID- 14960218
TI  - Mystery shopping in health service evaluation.
AB  - BACKGROUND: Over the last 5 years, primary care telephone triage systems have
      been introduced in the United Kingdom, United States, Australia, and most
      recently in New Zealand. Evaluation of the clinical safety of such systems poses
      a challenge for health planners and researchers. AIM: To evaluate the use of
      simulated patients in the assessment of aspects of clinical safety in a pilot New
      Zealand primary care telephone triage service. DESIGN OF STUDY: 'Mystery
      shopping', an evaluation strategy commonly used in market research, was adapted
      by using simulated patients for telephone triage service evaluation. SETTING: New
      Zealand. METHODS: Four scripted clinical scenarios were developed by academic
      general practitioners, validated in student teaching situations, and then used by
      simulated patients to make 101 telephone calls. The scenarios were designed to
      necessitate a referral to a medical practitioner for further investigation. The
      documentation kept by the callers was compared with the call records from the
      telephone triage company, and both were analysed for capture and handling of the
      clinical safety features of each scenario. In cases where the endpoint was not a
      medical assessment, possible reasons for this were explored. RESULTS: Records
      were retrieved for 85 telephone calls. Considerable triage variability was
      discovered. There were discrepancies between expected and actual triage outcomes
      with 51% of analysed calls resulting in a self-care recommendation. A number of
      reasons were identified both for the triage variability and the unpredicted
      outcomes. Audiotaping of consultations would have enhanced the credibility of the
      evaluation but it would have carried ethical constraints. CONCLUSION: Simulated
      patients can be used to evaluate the limitations of health services and to
      identify areas that could be addressed to improve patient safety. Evaluation of
      patient satisfaction with services is not sufficient alone to evaluate safety.

PMID- 14960219
TI  - Access to primary health care for Australian young people: service provider
      perspectives.
AB  - BACKGROUND: To adequately address the complex health needs of young people, their
      access to services, and the quality of services received, must be improved. AIMS:
      To explore the barriers to service provision for young people and to identify the
      training needs of primary healthcare service providers in New South Wales (NSW),
      Australia. DESIGN OF STUDY: A cross-sectional, qualitative study of the
      perspectives of a range of health service providers. SETTING: A range of primary
      healthcare organisations across NSW. METHODS: Samples of general practitioners
      (GPs), youth health workers, youth health coordinators, and community health
      centre staff were drawn from urban and rural clusters across NSW. Focus groups
      and interviews were used to identify barriers to service provision and the
      training needs of service providers. Data were tape recorded, transcribed, and
      analysed. RESULTS: Barriers to service provision among GPs and community health
      centre staff included inadequate time, flexibility, skills, and confidence in
      working with young people, and poor linkages with other relevant services.
      Training needs included better knowledge of and skills in adolescent health
      requirements, working with adolescents, and working with other services. Barriers
      to service provision for youth health workers and coordinators included lack of
      financial resources and infrastructure. There were few linkages between groups of
      service providers. CONCLUSION: Models of service provision that allow stronger
      linkages between service providers, sufficient time for consultation with young
      people, adequate training and support of health professionals, and flexibility of
      service provision, including outreach, should be explored and evaluated.

PMID- 14960220
TI  - Does changing from mercury to electronic blood pressure measurement influence
      recorded blood pressure? An observational study.
AB  - Mercury sphygmomanometers have been commonly used in primary care to measure
      blood pressure but are associated with bias. Electronic blood pressure machines
      are being introduced in many practices and have anecdotally been associated with
      higher recorded blood pressure. This study examined recorded blood pressure in
      four practices before and after electronic blood pressure machine introduction.
      No consistent change in mean blood pressure was apparent following their
      introduction, but there was a large and significant fall in terminal digit
      preference suggesting improved precision of recording.

PMID- 14960221
TI  - General practitioners and their possible role in providing spiritual care: a
      qualitative study.
AB  - We interviewed the general practitioners (GPs) of 40 patients with life
      threatening illnesses over the course of the last year of life. We asked them to
      identify their patients' holistic needs, and to discuss whether they considered
      that they had a role in providing 'spiritual care'. The GPs varied greatly in
      their understanding of their patients' experiences and needs. Most said that they
      had a role in providing spiritual care, but hesitated to raise spiritual issues
      with patients, mentioning lack of time, a feeling that they should wait for a
      cue, or being unprepared or unskilled.

PMID- 14960222
TI  - With luck, good doctors make a difference.
AB  - The luckiest general practitioners work in an ideal environment with a perfect
      patient population, their clinical intuitions are always correct, they face
      difficulties with total equanimity, and they get on with all their patients. In
      the real world one needs a lot of luck for things to go right. This paper applies
      the philosophical concept of 'moral luck' to the world of general practice.

PMID- 14960223
TI  - Mackenzie lecture. A dog's life.

PMID- 14960224
TI  - Management of meningitis.

PMID- 14960225
TI  - Worth doing badly? Sexual health promotion in primary care.

PMID- 14960226
TI  - [Advances in cancer proteomics study].
AB  - Proteomics has been widespreadly implanted into every field of life science and
      medicine as an important part of post-genomics era research. The development of
      theory and technology in proteomics has provided new ideas and research fields
      for cancer research. Proteomics can be used for not only elucidating the
      mechanism of carcinogenesis from the whole proteins of the tissue or cell but
      also seeking the biomarkers for diagnosis and therapy of cancer.

PMID- 14960227
TI  - [Effect of all trans retinoid acid (ATRA) on differentiation and apoptosis of HL
      60 cell].
AB  - BACKGROUND & OBJECTIVE: Treatment of premyeloid leukemia with all trans retinoid
      acid (ATRA) is a milestone in the history of chemotherapy of malignant tumor.
      Previous studies suggested that the mechanism of treating premyeloid leukemia
      with ATRA is inducing premyeloid leukemia cells to differentiate along myelocyte
      lineage, but the fate of differentiated tumor cells is not clear. This study was
      designed to investigate the relationship between the differentiation of HL-60
      induced by ATRA and apoptosis. METHODS: HL-60 cells influenced by ATRA (10
      micromol/L) capable of inducing differentiation for different time were used as
      the subject. The differentiation marker on the cell surface and cell cycle were
      analyzed using flow cytometry. The differentiated cells were identified by
      confocal microscope after having been stained with propidium iodide (PI).
      Meanwhile,the changes of the apoptosis of the cells induced by ATRA at different
      time were analyzed using flow cytometry. RESULTS: (1)With drug-inducing time
      increasing, the volume of the differentiated cells was enlarged gradually. After
      72 hours, the differentiated cells began to express differentiating marker CD11b
      and the nuclei morphology of the differentiated cells was changed. (2)After 96
      hours of drug-inducing, the induced cells began to show apoptosis peak, but when
      the cells was washed once after 72 hours of drug-inducing with RPMI 1640 medium
      and resuspended in RPMI 1640 medium supplemented with 10% fetal calf serum and
      then cultured in 5%CO2, 37 centigrade for 8 hours,the cells began to show
      apoptosis peak,and the apoptosis peak was higher than that of the cells after 96
      hours of drug-inducing. CONCLUSION: ATRA cannot induce HL-60 to achieve terminal
      differentiation,but the differentiation of HL-60 can be induced by ATRA and the
      differentiated leukemia cells are easy to apoptosis.

PMID- 14960228
TI  - [Construction and screening of human anti-idiotypic single chain antibodies of
      nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: The potential of anti-idiotypic antibody as a surrogate
      of tumor antigen for cancer therapy has been demonstrated in clinical
      investigations. But at present, many anti-idiotypic antibodies are mouse-original
      antibodies, which can cause human anti-mouse antibody (HAMA) response and
      decrease the curative effect. The objective of this study was to construct phage
      human anti-idiotypic antibody library and select beta type anti-idiotypic single
      chain antibodies bearing the internal image of the nasopharyngeal carcinoma (NPC)
      associated antigen to overcome human anti- mouse antibody response caused by
      application of mouse-original anti-idiotypic antibody. METHODS: Peripheral blood
      mononuclear cells (PBMCs) of patients with NPC were immunized in vitro by anti
      NPC monoclonal antibody FC2 and transformed by Epstein-Barr virus (EBV). V(H) and
      V(L) genes were amplified by RT-PCR and combined to single chain fragments of
      variable region (scFv) genes. ScFv genes were cloned into vector fUSE5 and
      transformed into E.coli MC1061 to construct the scFv-displaying phage library.
      After four rounds of panning with monoclonal antibody (mAb) FC2,the beta type Ab2
      scFv were selected by Sandwich ELISA and binding inhibition test. RESULTS: Of 10
      NPC patients, 8 patients showed their B cells immunized by FC2 and transformed by
      EBV produced anti-idiotypic antibodies to NPC. Five types of VH genes and 7 types
      of V(L) genes were obtained by RT-PCR amplification and then connected to form 14
      scFv genes. ScFv genes were transducted into E.coli MC1061. The library capacity
      was 1.5x10(8) clones. After panning, 270 phage clones were selected randomly and
      91 FC2-positive clones were obtained by Sandwich ELISA, the positive ratio was
      33.7%. Five clones,which might display beta type Ab2 scFv, were selected by
      binding inhibition test. CONCLUSION: The strategy for preparing phage anti
      idiotypic antibody library and selecting beta type Ab2 scFv by immunization in
      vitro, EBV transformation, and phage display technique is feasible, which provide
      a way for preparing cancer vaccine using beta type Ab2 scFv.

PMID- 14960229
TI  - [Effect of macrophage migration inhibitory factor (MIF) on expression of MMP
      2,MMP-9,and IL-8 in nasopharyngeal carcinoma cell strains].
AB  - BACKGROUND & OBJECTIVE: Although nasopharyngeal carcinoma (NPC) shows highly
      invasive and metastatic features than other head and neck carcinomas, the major
      relevant mechanism is still unknown. This study was designed to investigate
      whether the macrophage migration inhibitory factor (MIF) can affect the
      expression of matrix metalloproteinase 2, 9 (MMP-2, MMP-9) and interleukin 8 (IL
      8) in nasopharyngeal carcinoma (NPC) cell strains. METHODS: Two nasopharyngeal
      carcinoma cell strains, CNE-1 and CNE-2 were adopted in this study. The
      variations of expression percentages of MMP-2 or MMP-9-positive cells detected by
      flow cytometry in NPC cell strains with or without MIF activation were compared.
      Western blot analysis and reverse transcriptase-polymerase chain reaction (RT
      PCR) were applied to evaluate the protein and mRNA expression level of MMP-2 and
      MMP-9 in cell strains treated with and without MIF, respectively. The
      concentration of IL-8 in the supernatant of the cells with different treatments
      was tested using enzyme-linked immunosorbent assay (ELISA). RESULTS: (1)After
      treatment with MIF for 24 h, the percentage of MMP-9-positive cells was
      significantly increased in both CNE-1 (from 28.5+/-2.5% to 82.4+/-3.5%, P=0.001)
      and CNE-2 (from 32.8+/-3.5% to 86.1+/-1.6%, P=0.002). However, the percentages of
      MMP-2-positive cells did not significantly change between these two cell strains
      with or without MIF treatment (P >0.05). (2) The relative intensity of MMP-9
      protein expression was also enhanced in both cell strains (CNE-1:from 83.1+/-6.0
      to 242.9+/-22.9, P=0.002; CNE-2:from 84.4+/-4.3 to 278.9+/-29.7, P=0.003) and
      there was no significant difference in MMP-2 expression intensity either in CNE-1
      or CNE-2. (3)The IL-8 concentration in CNE-2 supernatant was 1201.8+/-593.3 pg/ml
      after treatment with MIF for 24 h, remarkably higher than that without treatment
      (32.7+/-20.1 pg/ml, P=0.026). However, there was no detectable difference of IL-8
      concentration found in CNE-1 (P=0.581). (4)The expression level of MMP-9 mRNA,
      but not of MMP-2 mRNA was significantly increased both in CNE-1 and CNE-2 after
      treatment with MIF. In addition, the IL-8 mRNA level was only enhanced in CNE-2
      but not in CNE-1. CONCLUSION: MIF cytokine might play an important role in
      neoplastic cell invasion and metastasis by up-regulating the expression of MMP-9
      and IL-8 in NPC cells through the pathway of activation of their gene
      transcription.

PMID- 14960230
TI  - [Expression of chemokine receptor CXCR4 in nasopharyngeal carcinoma cells].
AB  - BACKGROUND & OBJECTIVE: It was reported that chemokine receptor CXCR4 and its
      ligand stromal cell-derived factor 1(SDF-1) were involved in the proliferation,
      differentiation, and metastasis of tumor. This study was designed to observe the
      expression of CXCR4 in NPC cells with different differentiation grade and
      proliferative ability to primitively clarify the relationship between CXCR4 and
      the malignity of NPC cells. METHODS: After treated with all-trans-retinoic
      acid(RA) and telomerase antisense oligodeoxynucleotide (ASODN) respectively, the
      expression of CXCR4 mRNA and CXCR4 protein in NPC CNE1 and CNE2Z cells were
      determined by in situ hybridization and immunohistochemistry, respectively; the
      distribution of cell cycle was examined with flow cytometry and the proliferation
      of cells was identified by MTT method. RESULTS: CXCR4 mRNA and CXCR4 protein were
      strongly expressed in both CNE1 and CNE2Z cells, and their expression in CNE2Z
      cells was stronger than that in CNE1 cells. After treated with 1x10(-5) mol/L and
      1x10(-4) mol/L RA, CNE1 cells were arrested in G1 phase and CNE2Z cells in S
      phase, while the CXCR4 mRNA expression was significantly decreased in both CNE1
      and CNE2Z cells compared with control group cells (P< 0.01). The effect of 1x10(
      4) mol/L RA was more powerful than that of 1x10(-5) mol/L RA. After treated with
      ASODN, the proliferation of CNE1 and CNE2Z cells was inhibited, and the
      expression of CXCR4 protein was decreased compared with the control (P< 0.01).
      CONCLUSION: CXCR4 is highly expressed in NPC cells,and its expression was
      associated with differentiation grade and proliferation ability of NPC cells.

PMID- 14960231
TI  - [Screening and identification of ovarian carcinomas related genes].
AB  - BACKGROUND & OBJECTIVE: Ovarian cancer is the leading cause of death among
      gynecological malignancies. Up to now, little is known about specific tumor
      suppressor genes or oncogenes involved in the ovarian cancer genesis. Thus
      isolation of new candidate genes and characterization of their role in ovarian
      cancer genesis will be helpful for understanding the molecular mechanisms and
      developing protocols for early diagnosis and therapy of ovarian carcinomas. This
      study was developed to screen and identify genes related to ovarian carcinomas.
      METHODS: Modified mRNA differential display PCR and reverse Northern dot blot
      analysis were used to screen and identify different displayed genes between
      ovarian carcinoma tissue and normal ovarian tissue. The genes were sequenced and
      analyzed by bioinformatics software. With these gene fragments as probes, in situ
      hybridization was used to characterize specific gene expression difference
      between ovarian cancer tissues and normal ovarian tissues. RESULTS: Of 12
      differentially expressed genes, 5 were novel genes, 3 were chromosome genomic
      repeat sequences and the other 4 were known human genes. Furthermore, in situ
      hybridization analysis indicated that four genes, ZNF361, PSMA2, OCRC13 (a novel
      gene on chromosome 1) and OCRC4 (a novel gene on chromosome 9) were highly
      expressed in 36 samples of ovarian cancer tissues but not in 16 samples of normal
      ovarian tissues (P< 0.05). More interestingly, the gene OCRC4, with 99% sequence
      homology to mouse spindlin, a member of gene family specially expressed during
      gametogenesis, was highly expressed in 19 samples of ovarian cancer from total 36
      cases (53%), but not expressed in control samples. CONCLUSION: Our observations
      indicate that the four genes ZNF361, PSMA2, OCRC4, and OCRC13 may be ovarian
      cancer related genes. It is speculated that novel gene OCRC4 might also be a
      member of specific gene family, which plays roles during early period of embryo
      development and tumorigenesis.

PMID- 14960232
TI  - [Isolation of E1A-related drug-sensitive new genes by suppression subtractive
      hybridization].
AB  - BACKGROUND & OBJECTIVE: It has been well demonstrated that E1A, as a tumor
      suppression gene, is capable of inhibiting the growth and metastasis of different
      tumors, and reversing the malignant phenotype. Particularly, the gene possesses
      the ability to greatly enhance the drug-sensitivity of tumor cells to several
      antitumor agents, and also increase the radio-sensitivity. However, the
      associated genes through which E1A can exert its antitumor functions still remain
      unknown. The aim of this study was to isolate E1A anticancer-related genes,which
      were differentially expressed in drug-sensitive tumor cells using suppression
      subtractive hybridization (SSH). METHODS: To construct SSH library of human lymph
      node metastasis tumor cells (LN686) using the mRNA from LN686 cells treated by
      E1A protein and the parental LN686 cells as tester and driver, respectively.
      Positive clones in the library were selected randomly, and dot blot was used for
      the analysis of expression pattern of the differentially expressed-gene
      fragments. The sequences of cDNA fragments were analyzed and compared with that
      in GenBank. The mRNA levels of the novel genes in tester and driver were
      determined by semi-quantitative RT-PCR analysis. RESULTS: The SSH library
      contained about 7000 positive clones. Random analysis of 384 clones with PCR
      demonstrated that 362 clones contained inserted fragments. The consequence of dot
      blot demonstrated that these genes were over-expressed in the tester compared to
      the driver significantly. The 362 clones were sequenced and BLAST analysis was
      conducted, 10 clones are shown to be novel ESTs, and were registered in GenBank.
      The mRNA levels of the seven novel genes were over-expressed in LN686 cells
      treated by E1A protein compared to those of parental LN686 cells by semi
      quantitative RT-PCR analysis, and the difference of mRNA expression was
      approximately 3-8 times. CONCLUSION: Ten novel gene fragments were isolated by
      the SSH technology, and it provided the basis for further cloning their full-
      length genes and studying their functions.

PMID- 14960233
TI  - [Study of gene expression difference in lung carcinogenesis by cDNA microarray].
AB  - BACKGROUND & OBJECTIVE: Lung cancer is a kind of disease with high incidence and
      mortality, however its molecular mechanism is not clear yet. This study was
      designed to investigate gene expression differences among lung cancer tissues,
      lung paracancerous tissues,matched peripheral normal lung tissues and the
      metastases of lymph nodes, and to seek the relatively high expressed genes in
      lung carcinoma tissues, providing possible theoretical basis for early diagnosis
      and treatment of pulmonary carcinoma. METHODS: Fresh lung cancer tissue, lung
      paracancerous tissue, matched normal lung tissue and metastases of lymph nodes
      were deep-frozen in liquid nitrogen; their total RNA were extracted for reversed
      transcription cDNA probes, which were labeled and subsequently used to hybridize
      with cDNA microarray with 588 genes. Different gene expression profiles were
      obtained by analyzing the integrated density (ID) of spot images on the X-ray.
      RESULTS: In lung cancer tissues, 40 genes were detected to be differentially
      expressed, 36 of which such as early growth response protein 1 (EGR1), secreted
      apoptosis related protein 1 (SARP1) were upregulated while the others such as
      myeloid cell leukemia protein 1 (MCL1) were downregulated. The upregulated genes
      were mainly oncogene/suppressor gene, cell cycle regulatory gene, growth factors
      and apoptosis-related genes. In lung paracancerous tissues, 33 genes had
      different expression, 20 of which such as matrix metalloproteinase-9 (MMP-9) were
      upregulated, and the other 13 such as MCL1,endothelin 2 (ET2) were downregulated.
      In metastases of lymph nodes, there were 21 genes found to be differently
      expressed, 15 of which such as CD40 receptor-associated factor 1 (CRAF1) were
      downregulated while the rest were upregulated, and the upregulated genes (6 in
      15) were mainly the genes associated with adhesion molecules, matrix
      metalloproteinases and collagen. CONCLUSION: EGR1, SARP1, NDKA, etc. may be the
      key genes in pulmonary carcinogenesis course. At the same time, MMP9,
      thrombospondin 2 (TSP2), etc.may play an important role in pulmonary cancer
      metastasis and infiltration.

PMID- 14960234
TI  - [Inhibition of 8-chloroadenosine on proteasome activity of HL-60 cells].
AB  - BACKGROUND & OBJECTIVE: The proteasome is a multicatalytic proteinase complex in
      eukaryotic cells, and it can be used as a new target for screening anti-tumor
      drugs according to certain previous researches. The inhibition activity of 8-CA
      (8-chloroadenosine, a new anti-tumor drug synthesized in our lab) in sarcoma 180,
      hepatocarcinoma 22, and human gastric carcinoma xenograft tumor has been
      confirmed. However,the relationship between the mechanism of the inhibition and
      proteasome is still unclear. The present study was designed to explore the effect
      of 8-CA on 3 kinds of enzyme activities (chymotrypsin-like activity, trypsin-like
      activity, and peptidyl-glutamyl- peptide hydrolyzing activity) of 20S proteasome
      in human progranulocyte leukemia HL-60 cells. METHODS: HL-60 cells were treated
      with 8-CA at different concentrations for 24, 48, and 72 hours. Then total
      protein of HL-60 cells was extracted, and the three enzyme activities of 20S
      proteasomes in the total protein was examined. And the chymotrypsin-like activity
      of the purified proteasome from the total protein was also examined by
      immunoprecipitation. The enzyme activity was indicated by fluorescence absorbance
      (A) produced by degradation of specific substrates by proteasomes. RESULTS: In HL
      60 cells, three enzyme activities of the proteasomes were significantly inhibited
      after exposure to 0.1 micromol/L 8-CA for 48 hours; and the inhibition effect was
      concentration dependent. When the concentration of 8-CA reached 5 micromol/L, the
      inhibition rates of three proteasome activities (chymotrypsin-like
      activity,trypsin-like activity,and peptidyl- glutamyl-peptide hydrolyzing
      activity) were 44.96%, 54.52%, 48.36% for 48 hours and 67.53%, 70.48%, 64.08% for
      72 hours, respectively. The inhibition rate of 1 micromol/L and 5 micromol/L 8-CA
      on chymotrypsin-like proteasome activity of HL-60 cells for 48 hours were 68.14%
      (P< 0.01) and 92.75% (P< 0.001), respectively. CONCLUSION: 8-CA inhibits
      proteasome activity of HL-60 cells with a time- and concentration-dependent
      manner.

PMID- 14960235
TI  - [Establishment and comparison of two intraperitoneally transplanted human ovarian
      carcinoma models with immune reconstitution in severe combined immunodeficient
      mice].
AB  - BACKGROUND & OBJECTIVE: Ovarian carcinoma is leading cause of death in
      gynecologic malignancies. The survival rate cannot be improved after routine
      surgery, chemotherapy, and radiotherapy. Therefore biotherapy becomes the fourth
      treatment pattern for ovarian carcinoma. Adequate experimental models for the
      development of biologic therapeutic strategies are needed. Our purpose was to
      establish and compare two intraperitoneally transplanted human ovarian carcinoma
      models with human immune reconstitution in severe combined immunodeficient (SCID)
      mice. METHODS: Six and ten C.B17/SCID mice were intraperitoneally injected with
      human ovarian adenocarcinoma SKOV3 and SKOV3.ip1 cells, respectively. Their
      biological, histological, and immunological features were compared. Ascites of
      the mice in SKOV3.ip1 group was injected into other six mice. All the 22 SCID
      mice were intraperitoneally injected with human peripheral blood lymphocytes
      (PBL) to establish immune reconstituted model. RESULTS: The taken rates of the
      SKOV3 and SKOV3.ip1 groups were both 100%. The latent periods of tumor growth
      were 20-41 days and 22-30 days, respectively (P >0.05). While the mean survival
      time were 50-78 days and 32-43 days, respectively (P< 0.0001). 83.3% (5/6) of the
      mice injected with ascites of the mice in SKOV3.ip1 group successfully formed new
      tumor mass and ascites. Autopsy showed the tumors of the two models were
      widespread in pelvic cavity. The SKOV3.ip1 group also had 0.35-5.60 ml bloody
      ascites that was similar to the clinical behavior of most patients, while only
      0.2 ml in one mice of SKOV3 group. Histological results showed the tumors of the
      two groups remained the characteristics of serous papillary adenocarcinoma of
      human ovary, and immunohistochemistry staining showed the ovarian associated
      antigen OC166-9 were both positive. Human IgG were detected in 72.7% (16/22) of
      the mice, and human CD4(+) and CD8(+) T cells were positive in 54.5% (12/22) of
      the mice. CONCLUSION: The two intraperitoneally transplanted human ovarian
      carcinoma models had been established in human PBL reconstituted SCID mice. The
      SKOV3.ip1 model may be an ideal animal model for biotherapy research of ovarian
      carcinoma as it simulates the intraperitoneally disseminating behavior of human
      ovarian carcinoma in the patients with immune function, and it took relatively
      shorter time to be established.

PMID- 14960236
TI  - [Expression of HPV16-E6 and E7 oncoproteins in squamous cell carcinoma tissues of
      esophageal cancer and non-cancer tissues].
AB  - BACKGROUND & OBJECTIVE: Evidences indicate that high-risk type human
      papillomavirus (HPV) are closely associated with the carcinogenesis, progression
      and transformation of several kinds of human tumors. This study was designed to
      determine the expression of HPV16- E6 and E7 oncoproteins in normal tissues,
      dysplasia tissues, and carcinoma tissues of patients with esophageal cancer and
      to investigate the biological significance of high-risk type HPV in the
      esophageal squamous cell carcinogenesis. METHODS: HPV16-E6 and E7 oncoproteins
      were determined using immunohistochemical staining in normal mucosa tissues (70
      cases), dysplasia tissues (43 cases), and carcinoma tissues (18 cases). RESULTS:
      The positive rates of HPV16-E6 in the tissues of normal mucosa, dysplasia, and
      carcinoma of esophagus patients were 59.3%,88.4%,and 83.3%,respectively; the
      positive rates of HPV16-E7 protein were 62.1%, 90.7%, and 88.9%, respectively.
      The positive rates of HPV16-E6 and E7 in dysplasia and carcinoma of esophagus
      were significantly higher than those in normal mucosa (P< 0.05). Double
      expression of HPV16-E6 and E7 in normal mucosa was 25.7%, while in dysplasia and
      carcinoma were 88.3% and 83.3%,respectively. CONCLUSION: HPV16-E6 and E7 are
      highly associated with esophageal squamous cell carcinogenesis. And cooperation
      of HPV16-E6 and E7 may play an important role in genesis of esophageal squamous
      carcinoma.

PMID- 14960237
TI  - [Diallyl disulfide-induced G2/M arrest of human gastric cancer MGC803 cells
      involves activation of p38 MAP kinase pathways].
AB  - BACKGROUND & OBJECTIVE: p38 MAP kinase signal transduction pathway was thought to
      be involved in the G(2)/M arrest,however,the involved mechanisms were not clear.
      This study was designed to determine the role of p38 MAP kinase signal
      transduction pathways in diallyl disulfide (DADS)-induced G(2)/M arrest in human
      gastric cancer MGC803 cells and its related molecular mechanisms. METHODS: MGC803
      cells growth inhibition was measured by MTT assay. Phase distribution of cell
      cycle was analyzed by flow cytometry. Expression of Cdc25C, p38, phosphorylation
      of p38 (pp38) were determined by Western blot analysis. RESULTS: MTT assay showed
      that SB203580, a specific p38 MAPK inhibitor, blocked DADS-induced growth
      inhibition. Flow cytometry analysis revealed that treatment of MGC803 cells with
      30 mg/L DADS for 24 hours increased in the percentage of cells arrested in the
      G(2)/M phase from 9.3% to 39.4%(P< 0.05). Whereas in the presence of SB203580 the
      percentage decreased nearly one time, from 39.4% to 21.2% (P< 0.05). Western blot
      analysis showed that phosphorylation of p38 was increased 3.52-folds following
      treatment of MGC803 cells with 30 mg/L DADS for 20 minutes. At the same time, the
      total p38 abundance did not change. DADS treatment of MGC803 cells for 24 hours
      decreased the level of Cdc25C by 68%, and pretreatment of MGC803 cells with
      SB203580 partially reversed the downregulation of Cdc25C level by DADS (P< 0.05).
      CONCLUSION: DADS- induced G(2)/M arrest of MGC803 cells involves the activation
      of p38 MAP kinase pathway. Decreased Cdc25C protein expression by p38 played a
      crucial role in G(2)/M arrest after the treatment with DADS.

PMID- 14960238
TI  - [Expression of survivin in ovarian epithelial carcinoma and its correlation with
      expression of Fas and FasL].
AB  - BACKGROUND & OBJECTIVE: Recent research had shown that survivin, a new member of
      the inhibitors of apoptosis proteins (IAP) family, which also plays an important
      role in mitosis and cell apoptosis, and selectively overexpressed in common human
      cancers. This study was designed to examine the expression of survivin and its
      correlation with expression of Fas and FasL in ovarian epithelial carcinoma.
      METHODS: Immunohistochemical assay (SP method) was used to detect the expression
      of survivin, Fas and FasL genes in 84 ovarian cancer tissues, 39 benign tumors of
      ovary, and 20 normal ovary tissues. RESULTS: The level of expression of survivin
      was higher in the patients with ovarian cancer (63.1%) than that in the patients
      with benign tumor of ovary (30.8%) and normal ovary tissues (0.0%)(P< 0.01). The
      expression level of survivin was strongly correlated with clinical stage and poor
      differentiation. The expression of Fas in ovarian cancer (23.8%) was
      significantly lower than that of ovarian benign tumor (53.8%) (P< 0.01). The
      expression rate of FasL was significantly higher in ovarian cancer (44.0%) than
      that in ovarian benign tumor (23.1%)(P< 0.05). Positive survivin expression was
      strongly correlated with Fas and FasL expression. CONCLUSION: (1) High expression
      of survivin may plays an important role in the development of ovarian cancer and
      could be a useful prognostic maker for patients with ovarian cancer.(2) The
      abnormal expression of Fas and FasL in ovary cancer and their correlation with
      survivin suggested that survivin might be in cooperation with Fas and FasL,which
      involved in the pathogenesis of ovarian cancer.

PMID- 14960239
TI  - [Relationship between expression of hyaluronan and pathologic features of ovarian
      adenocarcinoma].
AB  - BACKGROUND & OBJECTIVE: Hyaluronan (HA) is one of the major components of extra
      cellular mesenchyma (ECM), which is secreted by several kinds of cells, including
      tumor cells. HA plays a role in cellular location and proliferation. It also
      takes part in the tumor cell motion and proliferation. It has been found that
      there was HA metabolism imbalance during the development of the solid tumors, and
      that, HA and its ligands might be related to tumor invasion, metastasis, and
      prognosis. The purpose of our research was to investigate the relationship among
      HA, the major ligand of cell adhesive molecule CD44, and pathologic types of
      ovarian adenocarcinoma. METHODS: HA and CD44 immunohistochemical assays were
      performed in the histopathologic specimens of 78 cases with ovarian
      adenocarcinoma and 24 cases with ovarian adenoma. Their expression in benign and
      malignant tumors with various histopathologic gradations were determined. Results
      were recorded as negative, weak positive, and strong positive. RESULTS: HA is
      mainly expressed in tumor stroma and extra-cellular mesenchyma, while cell
      membrane and cytoplasm were stained occasionally. In histologic sections,
      stronger expression was found in tumor stroma peripheral to carcinomatous nests.
      In total 102 specimens, positive HA expression in tumor stroma accounted for
      71.27%. The positive rate in malignant tumor was 83.33%; the strong positive rate
      was 41.03%. However, the positive expression rate in benign tumor was 27.27%. The
      level of stromal HA expression increased along with histologic gradation. The
      expression level in serous adenocarcinoma was higher than that in other
      pathologic types. Expression of HA in stroma and expression of CD44 in the tumor
      cells were significantly correlated; and the correlation of HA expression with
      histologic gradations was better than that of CD44. However, the expression of HA
      in tumor cells was low and unrelated to pathologic types, histopathologic
      gradations, and CD44 expression. CONCLUSION: High level of HA in the stroma of
      ovarian adenocarcinoma is related to tumor histological gradations and pathologic
      types.

PMID- 14960240
TI  - [Expression of Caspase-3 and Bcl-2 in bladder transitional carcinoma and their
      significance].
AB  - BACKGROUND & OBJECTIVE: Tumor growth was the result of cell excessive
      proliferation and lack of apoptosis. Apoptosis has been considered to be closely
      associated with Caspase-3 and Bcl-2. This study was designed to investigate the
      expression of Caspase-3 and Bcl-2 to evaluate their effects on the tumorigenesis
      and progression in bladder transitional carcinoma (BTCC). METHODS: The
      immunohistochemistry (SP method) was used to determine the expression of Caspase
      3 and Bcl-2 in 52 cases of BTCC and 10 normal bladder mucosas. RESULTS: The
      protein expression level of Caspase-3 in BTCC (53.8%,28/52) was significantly
      lower than that in normal bladder samples (90.0%,9/10). Caspase-3 expression
      level was correlated with the grades of BTCC (P< 0.05), but had no significant
      correlation with clinical stages. The protein expression of Bcl-2 in BTCC
      (51.9%,27/52) was significantly higher than that of normal bladder samples
      (20.0%,2/10), while its expression level was not related to stage and grade of
      BTCC (P >0.05). The expression of Caspase-3 is negatively related to that of Bcl
      2 (r(s)=-0.659,P< 0.01) in bladder tissues. CONCLUSION: Both over expression of
      Caspase-3 and descended expression of Bcl-2 may play an important role in the
      tumorigenesis and apoptotic regulation of bladder tissues.

PMID- 14960241
TI  - [Meta-analysis of relationship between lymph node micrometastasis and prognosis
      in stage I non-small cell lung cancer patients].
AB  - BACKGROUND & OBJECTIVE: Lymph node metastasis is an important factor for
      prognosis of non-small cell lung cancer (NSCLC). There were different opinions
      about what effect does lymph node micrometastasis have on prognosis. This study
      was designed to collect literatures of lymph node micrometastasis and prognosis
      in stage I NSCLC patients, in order to investigate their relationship. METHODS:
      The results from eight literatures on lymph node micrometastasis and prognosis
      from 1980 to 2002 were analyzed synthetically by meta-analysis. The cumulative
      cases were 536 NSCLC patients with stage I disease. RESULTS: The detection rate
      of lymph node micrometastasis ranged from 3.4% to 28.9%, and the rate of positive
      cases ranged from 20% to 70%. The 3-, 5-year over-survival rate for positive
      lymph node micrometastasis patients was worse than those of negative lymph node
      micrometastasis patients: odd ratios (ORs) were 4.16 (95%CI:2.32-7.46) and 3.57
      (95%CI:2.30-5.53), respectively (P< 0.01). CONCLUSION: Positive lymph node
      micrometastasis may be an adverse factor for post-operative prognosis of NSCLC
      stage I patients.

PMID- 14960242
TI  - [Expression of CD1a, CD80, CD86 in dendritic cell of tumor tissue and regional
      lymph node in esophageal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Dendritic cells are the important antigen presenting
      cell, and take part in the anti-tumor immunoreaction. This study was designed to
      investigate the expression of CD1a (specific marker) and CD80, CD86
      (costimulating molecules) in dendritic cell of tumor tissue and regional lymph
      node of esophageal carcinoma and to investigate the mechanisms by which tumors
      escape immune recognition. METHODS: The expression of CD1a, CD80, CD86 in
      dendritic cells of tumor tissues and paratumor tissues from 58 patients with
      esophageal carcinoma (clinical period I-II:27 cases,III-IV: 31
      cases;differentiation G(1-2): 37 cases,G3:21 cases;squamous cancer: 49
      cases,adenoid cancer: 9 cases;lymph node metastases present: 37 cases,lymph node
      metastases absent: 21 cases), inflammatory tissues from 11 patients with
      esophagitis, 12 normal esophageal tissues (as control), 31 regional lymph nodes
      with tumor and 34 regional lymph nodes without tumor were determined using flow
      cytometry. RESULTS: (1) The expression rates of CD1a, CD80, CD86 in tumor tissues
      (6.18+/-1.47, 5.37+/-1.13, 37.35+/-7.42) were less than those in normal tissues
      (10.28+/-2.11, 9.67+/-1.94, 48.76+/-10.23), the inflammatory tissues (11.89+/
      2.65, 10.46+/-1.79, 51.55+/-10.60), and the paratumor tissue (11.79+/-2.41,
      10.49+/-1.89, 9.78+/-12.31) (P< 0.01). (2) The expression rates of CD1a, CD80,
      CD86 in regional lymph node with tumor (8.34+/-1.66,6.78+/-1.42,41.70+/-8.71)
      were less than those in the lymph node without tumor (12.23+/-2.14, 10.82+/-2.11,
      59.63+/-12.52)(P< 0.01). (3) There was no significant difference in the
      expression rates of CD1a, CD80, CD86 between paratumor tissue, inflammatory
      tissue and normal esophageal tissues (P >0.05). (4) The expression of CD1a, CD80,
      CD86 were not associated with the clinical period, pathological type, and the
      lymph node metastases (P >0.05); but were associated with pathological
      differentiation (grade1-2 were higher than grade 3)(P< 0.01). CONCLUSION: (1) The
      number of dendritic cell of CD1a (+) decreases in tumor tissue and regional lymph
      node with tumor in esophageal carcinoma and the expression of CD80, CD86 are down
      regulated. (2) The lower the tumor differentiation grade, the less the number of
      CD1a(+) dendritic cell in tumor tissue and regional lymph node and the lower the
      expression of CD80, CD86 in tumor tissue.

PMID- 14960243
TI  - [Shrinkage of resected specimens of esophageal carcinoma].
AB  - BACKGROUND & OBJECTIVE: There are some kinds of shrinkage in resected specimens
      of esophageal carcinoma; however,there were few reports on its regularity. This
      study was designed to investigate the degree of shrinkage in resected specimens
      of esophageal carcinoma. METHODS: Specimens of seventy patients with esophageal
      squamous cell carcinoma who underwent resections in Cancer Center, Sun Yat-Sen
      University were collected. The length of the upper margin,the tumor,and the lower
      margin were measured with a ruler during operation before the esophagus was
      removed (in situ). After the esophagus was removed, the specimens were cut
      longitudinally on the side opposite the tumor, then the length of the upper
      margin, the tumor, and the lower margin were measured again without retraction.
      After 48 h fixation of 10% formalin (fixed), the length of the upper margin, the
      tumor, and the lower margin were measured again. RESULTS: After resection,the
      shrinkage rates of the upper margin, the tumor,and the lower margin were (40.71+/
      10.02)%,(83.59+/-16.57)%, and (58.41+/-12.03)% of their in situ length; after 48
      h fixation of 10% formalin, the shrinkage rates of the upper margin,the tumor,
      and the lower margin were (40.06+/-10.50)%, (80.92+/-15.88)%, and (54.83+/
      11.29)% of their in situ length (P< 0.05). CONCLUSION: The specimens of
      esophageal carcinoma shrink remarkably after removed and after formalin fixation.

PMID- 14960244
TI  - [Expression of RFC2 and PCNA in different gestational trophoblastic diseases].
AB  - BACKGROUND & OBJECTIVE: High expression of replication factor C (RFC) mRNA in
      hydatidiform mole and choriocarcinoma were detected previously with DNA
      microarray. Replication factor C subunit 2 (RFC2) was reported to be associated
      with DNA duplication, DNA repair, and the function of cellular checkpoint. The
      aim of current study was to investigate the expression levels of RFC2 and
      proliferating cell nuclear antigen (PCNA) in gestational trophoblastic diseases
      (GTD) and to explore the relationship of expressions of two proteins with GTD.
      METHODS: The expression of RFC2 and PCNA were detected with immunohistochemical
      method in 15 cases of normal villi, 38 cases of hydatidiform moles (HM), 42 cases
      of invasive moles (IM), and 18 cases of choriocarcinomas (CC). RESULTS: The
      expression of RFC2 and PCNA were significantly increased in HM, IM, and CC than
      in normal villi (P=0.000 for RFC2,P=0.004 for PCNA). There was no significant
      difference of the expression of RFC2 among HM, IM, and CC. The PCNA expression
      was significantly higher in CC than in HM (P=0.037). PCNA expression was
      significantly higher in the patients with malignantly transformed molar pregnancy
      than in the patients without malignantly transformed molar pregnancy (P=0.039).
      RFC2 expression in no preoperative chemotherapeutic group of gestational
      trophoblastic tumors (GTT) including IM and CC was significantly higher than that
      in the group with the chemotherapy of more than 3 cycles (P=0.028). Compared with
      patients at stageI, patients at stage III (WHO) had significantly increased
      expression of RFC2 (P=0.01). The level of RFC2 was higher in the patients with
      high risk in WHO prognostic scoring system than that in the patients with low
      risk (P=0.018). The levels of PCNA were significantly higher in the patients with
      high risk and middle risk than that in the patients with low risk (P=0.036 and
      P=0.048, respectively). The expression of PCNA protein was not associated with
      the preoperative chemotherapy and WHO stage of GTT. The RFC2 expression was
      positively correlated with the PCNA expression (P=0.000). CONCLUSION: The over
      expression of RFC2 and PCNA in GTD may be associated with the malignant
      transformation of HM and the behavior of trophoblastic tumor.

PMID- 14960245
TI  - [Clinical analysis of 8 cases of vulvar Paget's disease].
AB  - BACKGROUND & OBJECTIVE: Vulvar Paget's disease is a rare disease. It has a
      relatively high misdiagnosis rate and there are still controversies regarding its
      treatment. The objective of this study was to investigate its clinical features
      and summarize the experience of the management of this disease in order to gain a
      better acknowledge of this rare disease and improve its cure rate. METHODS: The
      clinical records of 8 cases of vulvar Paget's disease admitted in Cancer Center,
      Sun Yet-sen University from January 1964 to December 2001 were analyzed. RESULTS:
      The average age of 8 cases was 66.5 years, and the mean time from the onset of
      the disease to diagnosis was 5 years. Pathologically, intraepithelial Paget's
      disease was the commonest (5/8), followed by invasive Paget's disease (2/8) and
      Paget's disease with underlying adenocarcinoma (1/8). Eight cases underwent
      altogether 10 times of surgery, and radical vulvectomy was the most frequently
      used procedure (6/10). One case of Paget's disease with underlying adenocarcinoma
      died 21 months after surgery and 1 case of intraepithelial Paget's disease died
      of other etiology, 5 cases achieved long-term disease free survival, 1 case
      developed recurrence. CONCLUSION: Surgery is the first choice for the patients of
      vulvar Paget's disease. For those patients whose lesions are extensive,or old
      aged,or not suitable for long-term follow-up, a radical vulvectomy is more
      preferable and a lower recurrence rate is expected.

PMID- 14960246
TI  - [Stage IA1 squamous cell carcinoma of the uterine cervix: a report of 30 cases].
AB  - BACKGROUND & OBJECTIVE: The preoperative diagnosis and management of stage IA(1)
      squamous carcinoma of the cervix remains a controversial subject. The aim of this
      study was to discuss diagnosis and appropriate management options of this
      disease. METHODS: Clinical data and pathological materials of 30 patients with
      stage IA(1) squamous carcinoma of the cervix, who were treated in Cancer
      Hospital, Chinese Academy of Medical Science, Peking Union Medical College
      between 1992 to 2001, were reviewed. RESULTS: Seven of 30 patients (23.3%) had
      neither specific symptoms nor signs. Twenty-three patients had cytological
      examination with the positive rate of 86.9% (20/23). Colposcopy was performed in
      23 of the women; the accuracy of colposcopical impression was 78.2%(18/23). Of 10
      endocervical curettage (ECC) specimens, 4 cases had abnormal pathology. Among 30
      patients, 22 (73.3%) were treated with radical hysterectomy, 6 with simple
      hysterectomy, and 2 with cold conization only. There was no parametrical
      involvement and no positive vaginal margin in any of 28 patients who had
      hysterectomy. Lymphadenectomy was performed in 8 cases; the mean number of lymph
      nodes removed was 22, and no metastasis was found. The two conization specimens
      had free surgical margin. The preoperative diagnosis agreed with final diagnosis
      in only 56.7% (17/30); there was statistically significant difference between
      them (P< 0.01). During median 34 months follow-up (range, 17-111 months), no
      developed recurrences and no died from cancer. CONCLUSION: The diagnostic
      accuracy of colposcopically directed biopsy is quite poor for stage IA(1)
      cervical carcinoma. Cervical cold conization may increase the diagnostic accuracy
      and may be recommended for patients who desire conservation of fertility.

PMID- 14960247
TI  - [Evaluation of transvaginal ultrasonography-color Doppler energy imaging in
      surveillance of gynecologic malignant tumors after operation].
AB  - BACKGROUND & OBJECTIVE: Transvaginal ultrasonography (TVS) and color Doppler
      energy imaging (CDE) have been already applied in ultrasonography diagnosis
      extensively, but articles about the methods in surveillance of gynecologic
      malignant tumors after operation are few. The objective of this study was to
      evaluate TVS-CDE in surveillance of gynecologic malignant tumors after operation.
      METHODS: Fifty-four cases of gynecologic malignant tumors after operation, which
      were doubted as recurrent malignant tumors in clinic, were scanned with
      transabdominal ultrasonography (TAS), TVS, and TVS-CDE. The results were compared
      with that of pathology. Then their sensitivity, specificity,and accuracy were
      calculated, and the accuracy was compared by Chi-square test. RESULTS: Forty
      three cases were diagnosed as malignant tumors by TAS; Forty-six cases were
      diagnosed as malignant tumors by TVS,and the positions, sizes, characteristics of
      the recurrent malignant tumors could be depicted visually. Forty-seven cases were
      diagnosed as malignant tumors by TVS-CDE; Not only the blood flow characteristics
      of masses,but also more diagnostic information than TVS were provided. The
      sensitivity was 81.3%, 91.7%, and 95.9%, respectively; the specificity was
      33.3%,66.7%, and 83.3%, respectively; the accuracy was 75.9%, 88.9%, and 94.4%,
      respectively. Obviously, the accuracy of both TVS and TVS-CDE was higher than
      that of TAS(P< 0.05), but the accuracy of TVS and TVS-CDE was similar (P >0.05).
      CONCLUSION: TVS-CDE is helpful in the diagnosis of gynecologic malignant masses.
      It will be more effective in surveillance of recurrent gynecologic malignant
      tumors if it combined with CDE.

PMID- 14960248
TI  - [Comprehensive therapy for primary liver cancer: a report of 607 cases].
AB  - BACKGROUND & OBJECTIVE: Progress has been made in the field of early detection
      and early treatment of primary liver cancer (PLC), but many PLC patients remain
      unresectable, because their tumors are advanced or coexist with liver cirrhosis.
      Even if the tumor can be resected, the recurrent rate is more than 60%. This
      study aimed to investigate the efficacy of comprehensive therapy of PLC to
      improve the outcome. METHODS: A retrospective analysis of 607 patients with PLC
      received comprehensive treatment in Affiliated Tumor Hospital, Guangxi Medical
      University from 1985 to 2001. Among them, 423 cases were treated with various
      modes of hepatectomy: 134 with irregular hepatectomy, 95 with local radical
      resection, 123 with regular liver lobectomy or liver segment resection, 54 with
      semi-hepatectomy or more, 17 with hepatectomy combined with section of other
      organ. The other 184 nonresectable cases were treated with various combinations
      of therapy, such as ligation of hepatic artery, microwave coagulation, inter
      tumor injection of ethanol, cryosurgery, radio-frequency (RF), and
      intraperitoneal chemotherapy. RESULTS: 69.7%(423/607) of the whole group received
      liver resection, the overall mortality rate within one month after operation was
      1.2%(5/423), and the 3-, 5-, 10-year survival rates were 42.7%(218/511),
      37.5%(123/328), and 26.5%(26/98), respectively. For the resection group,the 3-, 5
      , 10-year survival rates were 57.2%(203/355), 51.3%(118/230), and 35.3%(24/68),
      respectively. For the nonresectable group, the 3-, 5-, 10-year survival rates
      were 9.6%(15/156), 5.1%(5/98), and 6.7%(2/30), respectively. CONCLUSION: Surgery
      predominant comprehensive therapy is effective modality for resectable PLC.
      Postoperative individualized comprehensive treatment can prevent tumor recurrence
      and improve postoperative effect.

PMID- 14960249
TI  - [Correlation of Skp2 and P27kip1 protein expression and clinicopathological
      features of prostate cancer].
AB  - BACKGROUND & OBJECTIVE: The F-box protein Skp2 is required for the ubiquitin
      mediated proteolysis of the cyclin-depended kinase inhibitor p27(kip1).
      Overexpression of Skp2 has been reported in many cancers, including breast
      carcinoma, gastric carcinoma, and prostate cancer. The purpose of this study was
      to investigate the correlation of Skp2 and p27(kip1) expression with the
      clinicopathological features of prostatic carcinoma, and the correlation between
      expression of Skp2 and p27(kip1) in prostate cancer. METHODS: Skp2 and p27(kip1)
      protein expression were evaluated in the tissues of 41 human prostatic carcinomas
      as well as 20 benign prostatic hyperplasia (BPH) using immunohistochemistry
      (EnVision method). RESULTS: The Skp2 labeling frequency in prostatic carcinoma
      (8.52%+/-2.40%) was significantly higher than that in BPH (0.21%+/-0.15%)(P<
      0.001). The Skp2 protein expression in prostatic carcinoma was positively
      correlated with preoperative serum prostate-specific antigen level
      (r=0.360,P=0.021), extraprostatic extension (r=0.570,P< 0.001), tumor stage
      (r=0.531, P< 0.001), and histological grade (r=0.514,P=0.001). The p27(kip1)
      labeling frequency in prostatic carcinoma(70.71%+/-4.25%) was significantly lower
      than that in BPH (97.21%+/-2.10%) (P< 0.001). The p27(kip1) protein expression in
      prostatic carcinoma was inversely correlated with preoperative serum prostate
      specific antigen level (r=-0.399,P=0.010), extraprostatic extension (r=-0.329,
      P=0.036), tumor stage (r=-0.453,P=0.003), and histological grade (r=
      0.290,P=0.046). Skp2 expression was inversely correlated with p27(kip1) in
      prostate cancer (rho=-0.572,P< 0.001). CONCLUSION: Expression of Skp2 protein may
      lead to decrease p27(kip1) level in human prostatic carcinoma, indicating its
      involvement in the development of human prostatic carcinoma. It may provide new
      targets for the therapy of prostate cancer.

PMID- 14960250
TI  - [Relationship of MAGE-A1 expression with Ki-67 and tumor-infiltrating lymphocyte
      response in non-small cell lung carcinoma].
AB  - BACKGROUND & OBJECTIVE: Recent studies revealed a possible close association
      between the expression of some members of tumor-specific antigen MAGE (melanoma
      antigen) family and actively proliferated infantile cells. But the correlation of
      MAGE-A1 expression with proliferation of tumor cells and immune response at host
      local site has not been reported to date. Our study was to investigate the
      expression of MAGE-A1 in non-small cell lung carcinoma (NSCLC), and its
      relationship with Ki-67 expression, tumor-infiltrating lymphocyte (TIL) response,
      histologic grade, and pathological type. METHODS: Thirty NSCLC samples in
      formalin-fixed, paraffin-embedded sections were examined for MAGE-A1, Ki-67 and
      TIL response using SP immunohistochemical technique. RESULTS: The positive
      expression rate of MAGE-A1 was 80.00%(24/30) with high expression rate of
      58.33%(14/24) and low expression rate of 41.67%(10/24). The positive expression
      rate of Ki-67 was 93.33%(28/30) with high expression rate of 57.14%(16/28) and
      low expression rate of 42.86% (12/28). TIL response was observed in 22 patients.
      There was a significant relationship between MAGE-A1 positive expression and Ki
      67 positive expression (rs=0.578, P< 0.005), as well as between MAGE-A1 positive
      expression and TIL response (rs=0.505, P< 0.005). However, MAGE-A1 expression was
      not significantly correlated with histologic grade and pathological type (P
      >0.05). CONCLUSION: The NSCLC cells with MAGE-A1 positive expression possess high
      proliferation activity; meanwhile, the up-regulation of MAGE-A1 indicates the
      increase of antigen in tumor cells and the increase of local TIL response,
      indicating that MAGE-A1 may have potential to be used as a target for
      immunotherapy in NSCLC patient.

PMID- 14960251
TI  - [Analysis of target localization errors in fractionated stereotactic radiotherapy
      for head and neck carcinoma].
AB  - BACKGROUND & OBJECTIVE: Accurate target localization is the essential requirement
      in the quality control in fractionated stereotactic radiotherapy (FSRT). This
      paper is to analyze the magnitude of errors in FSRT for head and neck carcinoma
      including the errors of CT localization, mechanical isocenter, setup of patients,
      and CT image. METHODS: The stereotactic radiotherapy treatment planning system
      (SRT-TPS), target simulator and head frame were used to check the errors of
      target localization during each radiation procedure. Five reference points were
      set randomly; the CT localization error was measured using the target simulator.
      Seven different mechanical angles of Gantry/Table were selected; the magnitude of
      isocentric errors of Philips SL-18 linear accelerator were acquired with films.
      Setup errors were collected by portal films. The image error possibly from CT
      image artifact was analyzed after scanning a self-made phantom by CT. RESULTS:
      The CT localization error was(1.5+/-0.4)mm. The maximal error of the mechanical
      isocenter was (1.0+/-0.6)mm according to the different mechanical gantry/table
      angles. The distance error of patient setup was (1.0+/-0.3)mm. The maximal total
      errors estimate was (2.1+/-0.8)mm. CONCLUSIONS: The effect of target localization
      of every procedure should be taken in account in FSRT, the results of the error
      analysis can be used to determinate the planning target volume in the treatment.

PMID- 14960252
TI  - [Circulating DNA, telomerase of circulating tumor cells and early diagnosis of
      tumors].
AB  - The increase of circulating DNA levels, the mutations of tumor characteristic
      genes and the telomerase expression of circulating tumor cells can be detected
      not only in advanced stage but also in early stage of tumors. The combinational
      detection of circulating DNA and telomerase of circulating tumor cells is useful
      for the early diagnosis of tumors.

PMID- 14960253
TI  - [Advance in diagnosis and management of local recurrent nasopharyngeal
      carcinoma].
AB  - Although radiotherapy is still the first measure of management of nasopharyngeal
      carcinoma and the curative effect is satisfactory at present, it is hard to avoid
      the recurrence of local-region in nasopharynx and/or neck lymph nodes in a part
      of patients after active treatment. Of them, the diagnosis and managements were
      difficult. This review analyzed the literatures of recent years. The factors of
      the recurrence, clinical characteristics, modern diagnosis technique and the
      salvage treatments of modern radiotherapy, chemotherapy, and surgery for
      recurrent nasopharyngeal carcinoma were introduced.

PMID- 14960254
TI  - Psychological treatment for insomnia in the regulation of long-term hypnotic drug
      use.
AB  - OBJECTIVES: To evaluate the clinical and cost impact of providing, in routine
      general practice settings, a cognitive-behaviour therapy (CBT) package for
      insomnia to long-term hypnotic drug users with chronic sleep difficulties; and to
      identify factors associated with variations in clinical outcomes. DESIGN: A
      pragmatic cluster randomised controlled trial with two treatment arms (a CBT
      treated 'sleep clinic' group, and a 'no additional treatment' control group),
      with post-treatment assessments starting at 3, 6 and 12 months. SETTING: Twenty
      three general practices in Sheffield, UK. PARTICIPANTS: In total, 209 patients
      (aged 31-92 years) with chronic sleep problems who had been receiving repeat
      hypnotic drug prescriptions for at least 1 month (mean = 13.4 years) were
      recruited into the trial. INTERVENTIONS: The intervention consisted of six 50
      minute sessions as follows: introduction and sleep assessment, basic sleep
      hygiene, stimulus control and sleep restriction procedures, progressive
      relaxation, cognitive treatments, and review and discharge. MAIN OUTCOME
      MEASURES: These included: global sleep quality [as measured by the Pittsburgh
      Sleep Quality Index (PSQI)], frequency of hypnotic drug use, mean dose of
      hypnotics consumed, health-related quality of life [as measured by the Short-Form
      36 (SF-36)], NHS service costs and overall cost utility. RESULTS: At 3- and 6
      month follow-ups, patients treated with CBT showed improved global PSQI scores as
      well as improvements in the SF-36 dimensions of vitality at 3 months and physical
      functioning and mental health at 6 months. CBT-treated patients also reported
      reductions in the frequency of hypnotic drug use compared with the control group,
      with many CBT-treated patients reporting zero drug use at the follow-up
      assessments. Clinical improvements were maintained within the CBT group at the 12
      month follow-up, with PSQI scores and the frequency of hypnotic drug use
      continuing to show significant reductions relative to the control group. Multiple
      regression analyses of PSQI scores within the sleep clinic group alone indicated
      that the magnitude of pre- to post-treatment change in overall sleep quality was
      closely related to Hospital Anxiety and Depression Scale depression scores at 3-,
      6-and 12-month follow-ups. In each model higher depression scores at baseline
      were associated with poorer treatment outcomes. No significant relationship was
      found between the patient's age and PSQI outcomes in any of these analyses.
      Within the sleep clinic group, reductions in drug use showed no significant
      association with the hypnotic product consumed. At the 3-month follow-up low
      frequency drug use was reported by 22.9% (8/35) of temazepam users, 33.3% (5/15)
      of nitrazepam users and 38.9% (7/18) of zopiclone users. The total cost of
      service provision was GBP154.40 per patient (1999/2000 prices). The mean
      incremental cost per quality-adjusted life-year (QALY) at 6 months was GBP3418;
      this figure was insensitive to changes in costs. A simple model also showed that
      extending the evaluation period beyond 6 months may improve the cost
      effectiveness of CBT. The incorporation of hidden costs associated with hypnotic
      drug treatment (e.g. accidents) also reduces the cost per QALY ratio, although to
      a much lesser degree. CONCLUSIONS: In routine general practice settings,
      psychological treatment for insomnia can improve sleep quality, reduce hypnotic
      drug use, and improve health-related quality of life at a favourable cost among
      long-term hypnotic users with chronic sleep difficulties. These positive outcomes
      appear robust over time, persisting for at least 1 year among the more treatment
      adherent patients. While these benefits may be reduced among those patients
      presenting with higher levels of psychological distress, the present study
      clearly indicates that older age per se presents no barrier to successful
      treatment outcomes. Further research should assess the long-term clinical and
      cost-effectiveness of psychological treatments for insomnia among non-hypnotic
      using patients, and establish the minimum psychological treatment input required.

PMID- 14960255
TI  - Clinical effectiveness and costs of the Sugarbaker procedure for the treatment of
      pseudomyxoma peritonei.
AB  - OBJECTIVES: This systematic review examines the clinical and cost-effectiveness
      of the Sugarbaker procedure for treating pseudomyxoma peritonei (PMP) and the
      costs of the procedure in the UK. DATA SOURCES: Electronic databases,
      bibliographies of related papers and experts in the field were used as sources
      for English language studies available up to September 2002. REVIEW METHODS:
      Evidence of the clinical effectiveness of the Sugarbaker procedure for PMP was
      synthesised through a narrative review with full tabulation of results of all
      included studies. The economic modelling used a Monte-Carlo simulation model
      populated with UK price data to estimate likely UK costs. RESULTS: Five
      retrospective case-series reports assessing the Sugarbaker procedure met the
      inclusion criteria for the review, although they were found to be of poor quality
      when judged against standard criteria for assessing methodological standard.
      There appears to be some benefit for people with PMP who undergo treatment with
      the Sugarbaker procedure. Commonly reported complications of the Sugarbaker
      procedure were anastomotic leaks, fistula formation, wound infection, small bowel
      perforations/obstructions and pancreatitis. One costing study of poor
      methodological quality and set in the USA was found. This study, together with UK
      unit price data and expert advice, was used to populate a Monte-Carlo simulation
      model to estimate the marginal cost of operating a service to provide treatment
      for PMP using the Sugarbaker technique rather than standard treatment. The
      results of the Monte-Carlo simulation model showed that the cost for one patient
      over a maximum of 5 years would be about 9700 British pounds, with a standard
      deviation of about 1300 British pounds (although costs incurred in setting up the
      specific service or training the staff were not included). The US study showed a
      ten-fold higher cost. The Monte-Carlo analysis showed that the variation around
      the mean was not very high. The most likely factor influencing the variation of
      the costs was the length of procedure. No sensitivity analysis could be done of
      the alternative treatment. CONCLUSIONS: The economic results should be seen as
      merely an example of the likely marginal costs of the Sugarbaker procedure, as
      more information about the current alternative is required. Trained and
      experienced staff are required to implement the procedure and inevitably time and
      cost will be involved in developing the appropriate teams. Although the procedure
      requires some specialist equipment and maintenance, such as smoke evacuators,
      these should have limited effect on setting up the service. PMP is a relatively
      rare condition with approximately 50 new cases per year in the UK and the impact
      of an increase in the demand for services should be limited. Evidence is needed
      for the effectiveness of maximal cytoreductive surgery compared with surgical
      debulking, using different intraoperative intraperitoneal chemotherapy
      strategies, and for the effectiveness of treatments in patients who have residual
      disease following maximal efforts at cytoreduction. Further research involving
      high-quality prospective cohort studies with economic evaluations would be
      valuable.

PMID- 14960256
TI  - Effectiveness and efficiency of guideline dissemination and implementation
      strategies.
AB  - OBJECTIVES: To undertake a systematic review of the effectiveness and costs of
      different guideline development, dissemination and implementation strategies. To
      estimate the resource implications of these strategies. To develop a framework
      for deciding when it is efficient to develop and introduce clinical guidelines.
      DATA SOURCES: MEDLINE, Healthstar, Cochrane Controlled Trial Register, EMBASE,
      SIGLE and the specialised register of the Cochrane Effective Practice and
      Organisation of Care (EPOC) group. REVIEW METHODS: Single estimates of
      dichotomous process variables were derived for each study comparison based upon
      the primary end-point or the median measure across several reported end-points.
      Separate analyses were undertaken for comparisons of different types of
      intervention. The study also explored whether the effects of multifaceted
      interventions increased with the number of intervention components. Studies
      reporting economic data were also critically appraised. A survey to estimate the
      feasibility and likely resource requirements of guideline dissemination and
      implementation strategies in UK settings was carried out with key informants from
      primary and secondary care. RESULTS: In total, 235 studies reporting 309
      comparisons met the inclusion criteria; of these 73% of comparisons evaluated
      multifaceted interventions, although the maximum number of replications of a
      specific multifaceted intervention was 11 comparisons. Overall, the majority of
      comparisons reporting dichotomous process data observed improvements in care;
      however, there was considerable variation in the observed effects both within and
      across interventions. Commonly evaluated single interventions were reminders,
      dissemination of educational materials, and audit and feedback. There were 23
      comparisons of multifaceted interventions involving educational outreach. The
      majority of interventions observed modest to moderate improvements in care. No
      relationship was found between the number of component interventions and the
      effects of multifaceted interventions. Only 29.4% of comparisons reported any
      economic data. The majority of studies only reported costs of treatment; only 25
      studies reported data on the costs of guideline development or guideline
      dissemination and implementation. The majority of studies used process measures
      for their primary end-point, despite the fact that only three guidelines were
      explicitly evidence based (and may not have been efficient). Respondents to the
      key informant survey rarely identified existing budgets to support guideline
      dissemination and implementation strategies. In general, the respondents thought
      that only dissemination of educational materials and short (lunchtime)
      educational meetings were generally feasible within current resources.
      CONCLUSIONS: There is an imperfect evidence base to support decisions about which
      guideline dissemination and implementation strategies are likely to be efficient
      under different circumstances. Decision makers need to use considerable judgement
      about how best to use the limited resources they have for clinical governance and
      related activities to maximise population benefits. They need to consider the
      potential clinical areas for clinical effectiveness activities, the likely
      benefits and costs required to introduce guidelines and the likely benefits and
      costs as a result of any changes in provider behaviour. Further research is
      required to: develop and validate a coherent theoretical framework of health
      professional and organisational behaviour and behaviour change to inform better
      the choice of interventions in research and service settings, and to estimate the
      efficiency of dissemination and implementation strategies in the presence of
      different barriers and effect modifiers.

PMID- 14960257
TI  - Systematic review of the clinical effectiveness and cost-effectiveness of
      capecitabine (Xeloda) for locally advanced and/or metastatic breast cancer.
AB  - OBJECTIVE: To examine the clinical effectiveness and cost-effectiveness of oral
      capecitabine for locally advanced and metastatic breast cancer in relation to its
      licensed indications. DATA SOURCES: Twenty-three electronic databases and other
      databases of ongoing research and Internet resources, bibliographies of retrieved
      articles and industry submissions. REVIEW METHODS: Two reviewers independently
      screened and assessed all titles and/or abstracts including economic evaluations.
      Randomised controlled trials (RCTs) and observational studies that investigated
      capecitabine monotherapy, in patients pretreated with an anthracycline-containing
      regimen or a taxane, or capecitabine in combination with docetaxel, in patients
      pretreated with an anthracycline-containing regimen, were included. The economic
      evaluation was based on data reported in the manufacturer's submission. RESULTS:
      For capecitabine monotherapy, 12 uncontrolled observational studies were
      identified. The methodological quality of the studies was low. Capecitabine
      demonstrated antitumour activity, but was associated with a particular risk of
      hand-foot syndrome and diarrhoea. Economic evaluation was hampered by the poor
      quality of the published studies, but compared indirectly with vinorelbine,
      capecitabine was associated with lower costs and improved patient outcomes. For
      capecitabine in combination with docetaxel, one RCT was identified. Combination
      therapy was superior to single-agent docetaxel in terms of survival, time to
      disease progression and overall response. Adverse events occurred more frequently
      with combination therapy. The economic evaluation demonstrated an overall
      improved QALY score for combination therapy with a slight reduction in costs.
      CONCLUSIONS: No conclusions could be drawn regarding the therapeutic benefit of
      capecitabine monotherapy; RCTs are required. Capecitabine appeared cost-effective
      compared with vinorelbine, but serious doubts remain; the poor quality of the
      trials may invalidate this conclusion. Based on limited evidence, combination
      therapy was more effective than single-agent docetaxel and likely to be cost
      effective, but was associated with higher incidences of hand-foot syndrome,
      nausea, diarrhoea and stomatitis.

PMID- 14960258
TI  - A systematic review of the role of bisphosphonates in metastatic disease.
AB  - OBJECTIVES: To identify evidence for the role of bisphosphonates in malignancy
      for the treatment of hypercalcaemia, prevention of skeletal morbidity and use in
      the adjuvant setting. To perform an economic review of current literature and
      model the cost effectiveness of bisphosphonates in the treatment of
      hypercalcaemia and prevention of skeletal morbidity. DATA SOURCES: Electronic
      databases (1966-June 2001). Cochrane register. Pharmaceutical companies. Experts
      in the field. Handsearching of abstracts and leading oncology journals (1999
      2001). REVIEW METHODS: Two independent reviewers assessed studies for inclusion,
      according to predetermined criteria, and extracted relevant data. Overall event
      rates were pooled in a meta-analysis, odds ratios (OR) were given with 95%
      confidence intervals (CI). Where data could not be combined, studies were
      reported individually and proportions compared using chi-squared analysis. Cost
      and cost-effectiveness were assessed by a decision analytic model comparing
      different bisphosphonate regimens for the treatment of hypercalcaemia; Markov
      models were employed to evaluate the use of bisphosphonates to prevent skeletal
      related events (SRE) in patients with breast cancer and multiple myeloma.
      RESULTS: For acute hypercalcaemia of malignancy, bisphosphonates normalised serum
      calcium in >70% of patients within 2-6 days. Pamidronate was more effective than
      control, etidronate, mithramycin and low-dose clodronate, but equal to high dose
      clodronate, in achieving normocalcaemia. Pamidronate prolongs (doubles) the
      median time to relapse compared with clodronate or etidronate. For prevention of
      skeletal morbidity, bisphosphonates compared with placebo, significantly reduced
      the OR for fractures (OR [95% CI], vertebral, 0.69 [0.57-0.84], non-vertebral,
      0.65 [0.54-0.79], combined, 0.65 [0.55-0.78]) radiotherapy 0.67 [0.57-0.79] and
      hypercalcaemia 0.54 [0.36-0.81] but not orthopaedic surgery 0.70 [0.46-1.05] or
      spinal cord compression 0.71 [0.47-1.08]. However, reduction in orthopaedic
      surgery was significant in studies that lasted over a year 0.59 [0.39-0.88].
      Bisphosphonates significantly increased the time to first SRE but did not affect
      survival. Subanalyses were performed for disease groups, drugs and route of
      administration. Most evidence supports the use of intravenous
      aminobisphosphonates. For adjuvant use of bisphosphonates, Clodronate, given to
      patients with primary operable breast cancer and no metastatic disease,
      significantly reduced the number of patients developing bone metastases. This
      benefit was not maintained once regular administration had been discontinued. Two
      trials reported significant survival advantages in the treated groups.
      Bisphosphonates reduce the number of bone metastases in patients with both early
      and advanced breast cancer. Bisphosphonates are well tolerated with a low
      incidence of side-effects. Economic modelling showed that for acute
      hypercalcaemia, drugs with the longest cumulative duration of normocalcaemia were
      most cost-effective. Zoledronate 4 mg was the most costly, but most cost
      effective treatment. For skeletal morbidity, Markov models estimated that the
      overall cost of bisphosphonate therapy to prevent an SRE was GBP250 and GBP1500
      per event for patients with breast cancer and multiple myeloma, respectively.
      Bisphosphonate treatment is sometimes cost-saving in breast cancer patients where
      fractures are prevented. CONCLUSIONS: High dose aminobisphosphonates are most
      effective for the treatment of acute hypercalcaemia and delay time to relapse.
      Bisphosphonates significantly reduce SREs and delay the time to first SRE in
      patients with bony metastatic disease but do not affect survival. Benefit is
      demonstrated after administration for at least 6-12 months. The greatest body of
      evidence supports the use of intravenous aminobisphosphonates. Further evidence
      is required to support use in the adjuvant setting.

PMID- 14960259
TI  - Collaborative studies for the establishment of reference substances for the
      microbiological assay of antibiotics.
AB  - Collaborative studies were initiated by the European Directorate for the Quality
      of Medicines (EDQM) to assign potency values for candidate European Pharmacopoeia
      Chemical Reference Substances (Ph. Eur. CRSs) used for the microbiological assay
      of antibiotics. The candidates were assayed against their respective
      International Standard (IS), using the methods by diffusion or turbidimetry.
      Potencies were assigned to all the antibiotics concerned, which were adopted by
      the European Pharmacopoeia Commission.

PMID- 14960260
TI  - Collaborative study for establishment of a global standard for the potency assay
      of human anti-D immunoglobulin.
AB  - An international collaborative study aimed at establishing a global standard for
      the potency assay of anti-D immunoglobulin was started in 2002. 25 laboratories
      participated in this study run under the common aegis of the World Health
      Organization, the United States Food and Drug Administration (US-FDA) and the
      European Directorate for the Quality of Medicines (EDQM). The potencies of three
      candidate materials and the US-FDA standard (lot 3) included for comparison were
      evaluated using AutoAnalyzer, competitive enzyme-linked immunoassay (competitive
      EIA), flow cytometric methods or own "in-house" methods. Critical reagent,
      standardised procedures and standardised assay design were provided for either
      method, where appropriate. Central statistical evaluation of the potency data
      submitted by the participants was performed using a parallel line model.
      Agreement between laboratories and assay methods for all samples was observed.
      Intra-laboratory variability was lowest for laboratories performing flow
      cytometry and highest for laboratories that performed their in-house methods.
      Inter-laboratory variability was acceptable for all samples when assayed by
      AutoAnalyzer, competitive (EIA) and flow cytometric methods. It was concluded
      that sample A is most suitable to serve as a global standard and that sample C
      could serve as a reserve European Pharmacopoeia (Ph. Eur.) Biological Reference
      Preparation (BRP) batch provided that suitable stability is demonstrated. Sample
      A was adopted by the Ph. Eur. Commission at its 115th session (March 2003) as the
      first Ph. Eur. BRP (available from the EDQM: catalog number Y0000219) with the
      assigned potency of 285 IU/ampoule.

PMID- 14960261
TI  - Collaborative study for establishment of a European Pharmacopoeia Biological
      Reference Preparation (BRP) for B19 virus DNA testing of plasma pools by nucleic
      acid amplification technique.
AB  - The goal of the collaborative study was to calibrate the B19 DNA content of a
      candidate Biological Reference Preparation (BRP) that is intended to be used for
      the validation of the analytical procedure, as threshold control and/or as
      quantitative reference material in the Nucleic Acid Amplification Technique (NAT)
      test of plasma pools for detection of B19 contamination. The candidate BRP was
      calibrated against the 1st International Standard for B19 DNA NAT assays.
      According to the European Pharmacopoeia monograph Human anti-D immunoglobulin,
      the threshold control needs to have a titre of 10( 4) IU/ml of B19 virus DNA. The
      lyophilised candidate BRP was prepared from 0.5 ml aliquots of a plasma pool
      spiked with B19 virus. The B19 virus originated from a "B19 virus window phase"
      blood donation (anti-B19 negative, B19-DNA high titre positive) and was diluted
      in a plasma pool tested negative by both serological and NAT assays for Hepatitis
      B Virus, Hepatitis C Virus and Human Immunodeficiency Virus 1 to obtain a B19-DNA
      concentration level in the range of 10( 6) copies/ml. The residual water content
      of the lyophilised candidate BRP was determined as 0.98 +/- 0.65% (mean +/-
      relative standard deviation). Sixteen laboratories (Official Medicine Control
      Laboratories, manufacturers of plasma derivatives, NAT test laboratories and NAT
      kit manufacturers) from nine countries participated. Participants were requested
      to test the candidate BRP and the International Standard (99/800) in four
      independent test runs on different days using their in-house qualitative and/or
      quantitative NAT methods. Sixteen laboratories reported results. Thirteen
      laboratories reported results from qualitative assays and 5 laboratories reported
      results from quantitative assays. Two laboratories reported results from both
      types of assay. For the qualitative assays a weighted combined potency of 5.64
      log( 10) IU/ml with 95 per cent confidence limits of +/- 0.17 log( 10) which
      corresponds to 67 to 150 per cent of the estimated potency was determined. For
      the quantitative assay the semi-weighted combination of the 5 potency estimates
      lead to a combined potency of 5.83 log( 10) IU/ml with 95 per cent confidence
      limits of +/- 0.04 log( 10) which corresponds to 91 to 110 per cent of the
      estimated potency. The semi-weighted combination of the results from both types
      of assay lead to a final potency estimate of 5.80 log( 10) IU/ml with 95 per cent
      confidence limits of +/- 0.05 log( 10) which corresponds to 86 to 117 per cent of
      the estimated potency. A threshold control suitable for quantitative testing of
      B19 DNA and reflecting the requirements of the European Pharmacopoeia monograph
      Human anti-D immunoglobulin should contain 104 IU/ml of B19 DNA. Taking into
      account the assigned titre of 5.80 log( 10) IU/ml (630.957 IU/ml), a dilution of
      10(-1.8) (1/63) of the candidate BRP should yield a positive response. This
      concentration was easily detected by all participating laboratories in all tests.
      The candidate BRP thus appeared to be suitable for the intended purpose. The
      candidate BRP was adopted as the European Pharmacopoeia BRP by the European
      Pharmacopoeia Commission at its session in June 2003 and is available from the
      European Directorate for the Quality of Medicines (Catalogue Number: Y0000285).

PMID- 14960262
TI  - Collaborative study for the validation of serological methods for potency testing
      of diphtheria toxoid vaccines-part 1.
AB  - A collaborative study on the evaluation of an alternative functional assay, the
      Vero cell method, to the Ph. Eur. in vivo challenge procedures for potency
      determination of diphtheria toxoid in 6 different combined vaccines was initiated
      in January 2001. The study was an extension of a previous study for the
      validation of serological methods for potency testing of tetanus toxoid vaccines
      for human use. To allow interim evaluation of test results and to monitor study
      progress, the project was divided into three consecutive phases. The results of
      Phase I and II studies are presented in this report. Pre-validation (Phase I)
      study, performed in two laboratories, indicated that comparable diphtheria
      potency estimates were obtained in the Ph. Eur. direct intradermal challenge
      assay in guinea pigs, in Vero cell assay and in indirect ELISA for five vaccines
      of different potencies (range of estimates: ca. 20-200 IU/ml). The correlation
      coefficients between the challenge assay and the Vero cell assay corresponded to
      those between the challenge assay and ELISA, confirming that the antibodies play
      an important role in protection and that predominantly protective/neutralising
      antibodies are present in guinea pigs, at the time point investigated. It was
      observed, for Vero cell assays, that about 16-35 (9-28 in Phase II study) fold
      lower titre of individual serum samples were obtained when using equine, rather
      than guinea pig reference serum. The study also provided preliminary information
      that sera from the same guinea pigs may be used for potency determination of both
      diphtheria and tetanus toxoid components of vaccines. In Phase II, another five
      laboratories analysed a subset of the vaccines included in Phase I study plus an
      additional vaccine. Four laboratories performed the lethal challenge assay and
      one laboratory carried out the intradermal challenge assay. All laboratories also
      performed the Vero cell assay and both ELISA for diphtheria antitoxin and ELISA
      for tetanus antitoxin. One laboratory also performed the tetanus ToBI assay. The
      correlation coefficient (r) between Vero cell assay and ELISA for diphtheria
      antitoxin ranged from 0.76 to 0.91 in the different laboratories. The correlation
      between diphtheria serological assays and challenge assays were confirmed
      satisfactory as ca. 90 per cent of serum-estimates lead to correct prediction of
      mortality. All laboratories had identical rankings of the vaccines in all
      serological assays and in the valid challenge assays. The ranking order was
      identical to assumed/provided potency for the highest and the lowest vaccine. Two
      of the vaccines had an inversion in some assays and laboratories. As these two
      vaccines have almost identical potencies in all assays, these inversions are not
      significant. As the vaccine doses were optimised for the diphtheria component,
      serum anti-tetanus toxoid/toxin activities varied widely between the vaccines,
      making it questionable to apply a parallel line model to calculate exact
      potencies. However, the dose levels used showed a clear regression and good
      linearity in general. DTaP vaccines containing the IPV component did not always
      meet the present Ph. Eur. requirements in the serological assays. It should be
      further investigated in the Phase III study if this is a general feature of such
      combined vaccines. Preliminary investigations on samples from two laboratories
      indicate that the neutralising activity of type 1, 2 and 3 polioviruses can also
      be detected, in a dose-dependent way. Further studies are in progress with serum
      samples from other laboratories. In the light of results obtained in the first
      two phases, it is recommended to proceed with Phase III study to investigate
      reliability of the in vitro assays. In Phase III it will also be further
      investigated whether the serological assays for D and T components are suitable
      for the control of the multi-component vaccines currently marketed in Europe.

PMID- 14960263
TI  - Collaborative study for the validation of serological methods for potency testing
      of diphtheria toxoid vaccines - extended study: correlation of serology with in
      vivo toxin neutralisation.
AB  - Phase I of BSP034 collaborative study was extended in two laboratories to include
      correlation of serology with in vivo toxin neutralisation test (TNT) using 2
      separate sets of 20 serum pools, produced in-house. The study investigated the
      extent to which the in vitro methods for diphtheria antibodies, Vero cell assay
      and diphtheria enzyme-linked immunosorbent assay for diphtheria antitoxin (D
      ELISA), can detect neutralising antibodies by comparison with TNT in guinea pigs.
      The study was also performed to compare the antibody neutralising potency
      obtained in relation to guinea pig (GP) or equine (DI) antitoxin standard. In
      addition, the study provided an opportunity to compare ELISA for tetanus
      antitoxin (T-ELISA) and TNT assay for detection of anti-tetanus antibodies, from
      the same set of serum pools. The data obtained show that antitoxin potency
      obtained by Vero cell assay, D-ELISA and T-ELISA using the same GP standard,
      highly correlated with neutralising potency as determined in respective TNT
      assays. Vero cell assay with DI provided estimates that also correlated with
      neutralising potency, but were of significantly lower titre. Since reference to
      DI standard is widely used in serodiagnosis, as well as in clinical studies where
      diphtheria antitoxin titres obtained in the Vero cell method are taken as
      surrogate markers for vaccine efficacy, it should be investigated if a similar
      difference is also observed for human serology.

PMID- 14960264
TI  - Establishment of European Pharmacopoeia (Ph. Eur.) Biological Reference
      Preparations (BRP) batch 2 for rDNA hepatitis B vaccine (method A and B).
AB  - A collaborative study was initiated by the European Directorate for the Quality
      of Medicines (EDQM), to assign a potency value for candidate batch 2 of European
      Pharmacopoeia (Ph. Eur.) Biological Reference Preparation (BRP) for Hepatitis B
      (rDNA) antigen in vitro assays, for both method A and method B by calibrating
      them against the Ph. Eur. BRPs, batch 1 for methods A and B respectively. The
      study was prompted by the observation that the first batch of BRP for method B
      appeared to have lost potency over time. BRP 1 for method A showed no loss in
      potency, however stocks of the material were nearing depletion. Eleven
      laboratories participated in the study and all reported results. Participants
      performed 3 independent assays using both method A and method B. Method A was
      used to assess BRPs for method A and method B was used to assess BRPs for method
      B. Since BRP 1B was suspected to have lost potency, an additional sample was
      included in the method B test in an attempt to clarify the situation. BRP 1B was
      also assayed in method A against BRP 1A in the hope of also attaining further
      information by comparing the results from this study to those obtained in the
      original study to establish the first batch of BRP [1]. Although it was not the
      primary aim of this study to correlate in vitro potency with the immunogenicity
      assay in mice, a number of interested parties also performed the mouse in vivo
      assay to obtain data on the behaviour of the candidate BRPs in this assay. For
      method A, potency estimates were satisfactory in terms of repeatability and
      reproducibility. The candidate material was therefore assigned a value of 16.6
      micrograms/ml. For method B, it appeared that the observation of reduced in vitro
      potency of BRP1 was confirmed. Despite the attempt to clarify the situation with
      additional studies, it was not possible to assign a potency value with the
      results obtained. A small-scale collaborative study will be organised to
      determine an appropriate value for the candidate BRP for method B. The results
      from the in vivo study while highly variable showed no evidence of a shift in the
      in vivo potency for either BRP 1A or BRP 1B. It should be noted that the in vitro
      method for determination of hepatitis B vaccine potency is under revision due to
      the discontinuation of the Auszyme kit from Abbott, which is required to perform
      the current assays. Once an alternative assay has been established, the
      suitability of the reference preparations or establishment of new reference
      preparations will be required. The candidate material for method A BRP was
      adopted by the European Pharmacopoeia Commission at its session in November 2003,
      as the European Pharmacopoeia Hepatitis B vaccine (rDNA) method A, batch 2.

PMID- 14960265
TI  - Control of Clostridium perfringens vaccines using an indirect competitive ELISA
      for the epsilon toxin component - examination of the assay by a collaborative
      study.
AB  - Investigations on the replacement of the mouse neutralisation test for proving
      vaccine batches of Clostridium (C.) perfringens toxoid vaccines were performed
      since several years. The European Pharmacopoeia (Ph. Eur.) monograph Clostridium
      perfringens vaccines for veterinary use (0363) is prescribing a potency test by
      immunisation of rabbits and checking the induction of specific antibodies against
      the toxins in a mouse neutralisation test. Since the monograph was revised,
      immunochemical methods are favoured to detect directly specific antibodies in the
      rabbit sera. An indirect competitive ELISA using a monoclonal antibody was
      established at the Paul-Ehrlich-Institut for the detection of antibodies against
      the epsilon toxin component of C. perfringens. It was revised using the
      Clostridia rabbit antiserum Ph. Eur. Biological Reference Preparation (BRP) Batch
      1 as reference serum. With a defined content of 11 International Units (IU) of C.
      perfringens epsilon antitoxin this reference serum enables the calculation of the
      potency of rabbit sera under test. For the collaborative study vaccine products
      of different composition licensed for the German and European markets were used.
      Seven international laboratories were included. Aim was to make a prediction on
      the transferability and precision of the test method. The results showing a
      satisfactory intermediate precision and transferability of the test confirmed the
      applicability of the ELISA method for the batch control of C. perfringens
      vaccines. Therefore a replacement of the mouse neutralisation test is available.

PMID- 14960266
TI  - Germline imprinting: battle of the sexes or battle of the X's?
AB  - The X chromosome is largely inactivated in spermatogenesis of heterogametic
      males, and in multiple phyla it encodes few genes specifically expressed in the
      male germline. Writing in Nature Genetics, Bean et al. report a parallel between
      male germline X inactivation in nematodes and a fungal gene-silencing mechanism
      that alters the way we view the evolution of both phenomena.

PMID- 14960267
TI  - When Ras signaling reaches the mediator.
AB  - Numerous sequence-specific DNA binding proteins that couple extracellular stimuli
      to transcriptional regulation have been described. Less well understood is how
      these transcriptional regulators interact with the Mediator complex to initiate
      transcription and how those interactions are coordinated with the activation of
      signaling pathways. Recent work has begun to shed light on this important area of
      research.

PMID- 14960268
TI  - Kinases and circadian clocks: per goes it alone.
AB  - In the January 30, 2004, issue of Molecular Cell, Nawathean and Rosbash describe
      how kinases cooperate to create a small but active pool of PER that can localize
      to the nucleus and act on its own in a transcriptional feedback loop underlying
      the Drosophila circadian clock.

PMID- 14960269
TI  - Endosomal protein traffic meets nuclear signal transduction head on.
AB  - Rab5 plays a key role in controlling protein traffic through the early stages of
      the endocytic pathway. Previous studies on the modulators and effectors of Rab5
      protein function have tied the regulation of several signal transduction pathways
      to the movement of protein through endocytic compartments. In the February 6,
      2004, issue of Cell, Miaczynska et al. describe a surprising new link between
      Rab5 function and the nucleus by uncovering two new Rab5 effectors as potential
      regulators of the nucleosome remodeling and histone deacetylase protein complex
      NuRD/MeCP1.

PMID- 14960270
TI  - A breath of fresh air for cyclin D/Cdk4: triggering growth via Hph.
AB  - Activation of Cyclin D/Cdk4 stimulates progression through the G1-S phase of the
      cell cycle in many organisms. In Drosophila, Cyclin D/Cdk4 also induces cell
      growth independently of cell cycle progression. In this issue of Developmental
      Cell, Frei and Edgar reveal that Cyclin D/Cdk4-stimulated growth requires Hph, a
      prolyl hydroxylase that is a key component of a cell's ability to respond to
      hypoxia.

PMID- 14960271
TI  - A role for serotonin in the mammary gland.
AB  - In this issue of Developmental Cell, Matsuda et al. describe an unexpected
      function for the neurotransmitter serotonin in the mammary gland, in which local
      synthesis of serotonin by the mammary epithelium plays an important role in the
      negative feedback loop opposing stimulation of mammary gland development and
      lactation by prolactin. This feedback loop is important for suppression of milk
      secretion in response to filling of the gland. This novel finding adds to the
      growing body of evidence for diverse functions of serotonin.

PMID- 14960273
TI  - The lateral signal for LIN-12/Notch in C. elegans vulval development comprises
      redundant secreted and transmembrane DSL proteins.
AB  - The vulval precursor cells (VPCs) are spatially patterned by a LET-23/EGF
      receptor-mediated inductive signal and a LIN-12/Notch-mediated lateral signal.
      The lateral signal has eluded identification, so the mechanism by which lateral
      signaling is activated has not been known. Here, we computationally identify ten
      genes that encode potential ligands for LIN-12, and show that three of these
      genes, apx-1, dsl-1, and lag-2, are functionally redundant components of the
      lateral signal. We also show that transcription of all three genes is initiated
      or upregulated in VPCs in response to inductive signaling, suggesting that direct
      transcriptional control of the lateral signal by the inductive signal is part of
      the mechanism by which these cell signaling events are coordinated. In addition,
      we show that DSL-1, which lacks a predicted transmembrane domain, is a natural
      secreted ligand and can substitute for the transmembrane ligand LAG-2 in
      different functional assays.

PMID- 14960272
TI  - Early steps in the development of the forebrain.
AB  - The tremendous complexity of the adult forebrain makes it a challenging task to
      elucidate how this structure forms during embryonic development. Nevertheless, we
      are beginning to understand how a simple epithelial sheet of ectoderm gives rise
      to the labyrinthine network of cells that constitutes the functional forebrain.
      Here, we discuss early events in forebrain development--those that lead to the
      establishment of the anterior neural plate and the regional subdivision of this
      territory into the different domains of the prospective forebrain.

PMID- 14960274
TI  - Serotonin regulates mammary gland development via an autocrine-paracrine loop.
AB  - Mammary gland development is controlled by a dynamic interplay between endocrine
      hormones and locally produced factors. Biogenic monoamines (serotonin, dopamine,
      norepinephrine, and others) are an important class of bioregulatory molecules
      that have not been shown to participate in mammary development. Here we show that
      mammary glands stimulated by prolactin (PRL) express genes essential for
      serotonin biosynthesis (tryptophan hydroxylase [TPH] and aromatic amine
      decarboxylase). TPH mRNA was elevated during pregnancy and lactation, and
      serotonin was detected in the mammary epithelium and in milk. TPH was induced by
      PRL in mammosphere cultures and by milk stasis in nursing dams, suggesting that
      the gene is controlled by milk filling in the alveoli. Serotonin suppressed beta
      casein gene expression and caused shrinkage of mammary alveoli. Conversely, TPH1
      gene disruption or antiserotonergic drugs resulted in enhanced secretory features
      and alveolar dilation. Thus, autocrine-paracrine serotonin signaling is an
      important regulator of mammary homeostasis and early involution.

PMID- 14960275
TI  - Regulation of segmental patterning by retinoic acid signaling during Xenopus
      somitogenesis.
AB  - Somites, the segmented building blocks of the vertebrate embryo, arise one by one
      in a patterning process that passes wavelike along the anteroposterior axis of
      the presomitic mesoderm (PSM). We have studied this process in Xenopus embryos by
      analyzing the expression of the bHLH gene, Thylacine1, which is turned on in the
      PSM as cells mature and segment, in a pattern that marks both segment boundaries
      and polarity. Here, we show that this segmental gene expression involves a PSM
      enhancer that is regulated by retinoic acid (RA) signaling at two levels. RA
      activates Thylacine1 expression in rostral PSM directly. RA also activates
      Thylacine1 expression in the caudal PSM indirectly by inducing the expression of
      MKP3, an inhibitor of the FGF signaling pathway. RA signaling is therefore a
      major contributor to segmental patterning by promoting anterior segmental
      polarity and by interacting with the FGF signaling pathway to position segmental
      boundaries.

PMID- 14960276
TI  - A dual role for Ikk alpha in tooth development.
AB  - IKK alpha is a component of the I kappa B kinase (IKK) complex that plays a key
      role in the activation of NF-kappa B. In Ikk alpha mutant mice and mice
      expressing a transdominant negative mutant of I kappa B alpha (cI kappa B alpha
      Delta N), molars have abnormal cusps, indicating that Ikk alpha is involved in
      cusp formation through the NF-kappa B pathway. However, Ikk alpha mutant incisors
      also have an earlier phenotype where epithelium evaginates outward into the
      developing oral cavity rather than invaginating into the underlying mesenchyme. A
      similar evagination of epithelium was also observed in whisker development,
      suggesting that Ikk alpha contributes to the direction of epithelial growth
      during the early stages of development in many ectodermal appendages. Since cI
      kappa B alpha Delta N mice have normal incisor epithelial invagination, Ikk
      alpha's role appears to be NF-kappa B independent. Changes in Notch1, Notch2,
      Wnt7b, and Shh expression found in incisor epithelium of Ikk alpha mutants
      suggest that this NF-kappa B-independent function is mediated by Notch/Wnt/Shh
      signaling pathways.

PMID- 14960277
TI  - A "Whirly" transcription factor is required for salicylic acid-dependent disease
      resistance in Arabidopsis.
AB  - Transcriptional reprogramming is critical for plant disease resistance responses;
      its global control is not well understood. Salicylic acid (SA) can induce plant
      defense gene expression and a long-lasting disease resistance state called
      systemic acquired resistance (SAR). Plant-specific "Whirly" DNA binding proteins
      were previously implicated in defense gene regulation. We demonstrate that the
      potato StWhy1 protein is a transcriptional activator of genes containing the PBF2
      binding PB promoter element. DNA binding activity of AtWhy1, the Arabidopsis
      StWhy1 ortholog, is induced by SA and is required for both SA-dependent disease
      resistance and SA-induced expression of an SAR response gene. AtWhy1 is required
      for both full basal and specific disease resistance responses. The transcription
      factor-associated protein NPR1 is also required for SAR. Surprisingly, AtWhy1
      activation by SA is NPR1 independent, suggesting that AtWhy1 works in conjunction
      with NPR1 to transduce the SA signal. Our analysis of AtWhy1 adds a critical
      component to the SA-dependent plant disease resistance response.

PMID- 14960278
TI  - Drosophila cyclin D/Cdk4 requires Hif-1 prolyl hydroxylase to drive cell growth.
AB  - The Drosophila cyclin-dependent protein kinase complex Cyclin D/Cdk4 induces cell
      growth (accumulation of mass) as well as proliferation (cell cycle progression).
      To understand how CycD/Cdk4 promotes growth, we performed a screen for modifiers
      of CycD/Cdk4-driven overgrowth in the eye. Loss-of-function mutations in Hif-1
      prolyl hydroxylase (Hph), an enzyme involved in the cellular response to hypoxic
      stress, dominantly suppress the growth but not the proliferation function of
      CycD/Cdk4. hph mutant cells are defective for growth, and, remarkably, ectopic
      expression of Hph is sufficient to increase cellular growth. Epistasis analysis
      places Hph downstream of CycD/Cdk4. Overexpressed CycD/Cdk4 causes an increase in
      Hph protein in tissues where Hph induces growth, suggesting a mechanism whereby
      Hph levels are regulated posttranscriptionally in response to CycD/Cdk4. Our data
      suggest that Hph, in addition to its function in hypoxic response, is a regulator
      of cellular growth and that it is a key mediator for CycD/Cdk4.

PMID- 14960279
TI  - Aurora B regulates MCAK at the mitotic centromere.
AB  - Chromosome orientation and alignment within the mitotic spindle requires the
      Aurora B protein kinase and the mitotic centromere-associated kinesin (MCAK).
      Here, we report the regulation of MCAK by Aurora B. Aurora B inhibited MCAK's
      microtubule depolymerizing activity in vitro, and phospho-mimic (S/E) mutants of
      MCAK inhibited depolymerization in vivo. Expression of either MCAK (S/E) or MCAK
      (S/A) mutants increased the frequency of syntelic microtubule-kinetochore
      attachments and mono-oriented chromosomes. MCAK phosphorylation also regulates
      MCAK localization: the MCAK (S/E) mutant frequently localized to the inner
      centromere while the (S/A) mutant concentrated at kinetochores. We also detected
      two different binding sites for MCAK using FRAP analysis of the different MCAK
      mutants. Moreover, disruption of Aurora B function by expression of a kinase-dead
      mutant or RNAi prevented centromeric targeting of MCAK. These results link Aurora
      B activity to MCAK function, with Aurora B regulating MCAK's activity and its
      localization at the centromere and kinetochore.

PMID- 14960280
TI  - Ozz-E3, a muscle-specific ubiquitin ligase, regulates beta-catenin degradation
      during myogenesis.
AB  - The identities of the ubiquitin-ligases active during myogenesis are largely
      unknown. Here we describe a RING-type E3 ligase complex specified by the adaptor
      protein, Ozz, a novel SOCS protein that is developmentally regulated and
      expressed exclusively in striated muscle. In mice, the absence of Ozz results in
      overt maturation defects of the sarcomeric apparatus. We identified beta-catenin
      as one of the target substrates of the Ozz-E3 in vivo. In the differentiating
      myofibers, Ozz-E3 regulates the levels of sarcolemma-associated beta-catenin by
      mediating its degradation via the proteasome. Expression of beta-catenin mutants
      that reduce the binding of Ozz to endogenous beta-catenin leads to Mb-beta
      catenin accumulation and myofibrillogenesis defects similar to those observed in
      Ozz null myocytes. These findings reveal a novel mechanism of regulation of Mb
      beta-catenin and the role of this pool of the protein in myofibrillogenesis, and
      implicate the Ozz-E3 ligase in the process of myofiber differentiation.

PMID- 14960281
TI  - Isoprenoids control germ cell migration downstream of HMGCoA reductase.
AB  - 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAr) provides attractive
      cues to Drosophila germ cells, guiding them toward the embryonic gonad. However,
      it remains unclear how HMGCoAr mediates this attraction. In a genomic analysis of
      the HMGCoAr pathway, we found that the fly genome lacks several enzymes required
      for cholesterol biosynthesis, ruling out cholesterol and cholesterol-derived
      proteins as mediators of PGC migration. Genetic analysis of the pathway revealed
      that two enzymes, farnesyl-diphosphate synthase and geranylgeranyl-diphosphate
      synthase, required for the production of isoprenoids, act downstream of HMGCoAr
      in germ cell migration. Consistent with a role in geranylgeranylation, embryos
      deficient in geranylgeranyl transferase type I show germ cell migration defects.
      Our data, together with similar findings in zebrafish, implicate an isoprenylated
      protein in germ cell attraction. The specificity and evolutionary conservation of
      the HMGCoAr pathway for germ cells suggest that an attractant common to
      invertebrates and vertebrates guides germ cells in early embryos.

PMID- 14960282
TI  - Germ cell migration in zebrafish is dependent on HMGCoA reductase activity and
      prenylation.
AB  - Hydroxymethylglutaryl coenzyme A reductase (HMGCoAR) is required for isoprenoid
      and cholesterol biosynthesis. In Drosophila, reduced HMGCoAR activity results in
      germ cell migration defects. We show that pharmacological HMGCoAR inhibition
      alters zebrafish development and germ cell migration. Embryos treated with
      atorvastatin (Lipitor) exhibited germ cell migration defects and mild morphologic
      abnormalities. The effects induced by atorvastatin were completely rescued by
      prior injection of mevalonate, the product of HMGCoAR activity, or the
      prenylation precursors farnesol and geranylgeraniol. In contrast, squalene, a
      cholesterol intermediate further down the pathway, failed to rescue statin
      induced defects. Moreover, pharmacologic inhibition of geranylgeranyl transferase
      1 (GGT1) protein prenylation activity also resulted in abnormal germ cell
      migration. Thus, our pharmacological inhibition-and-rescue approach provided
      detailed information about the elements of isoprenoid biosynthesis that
      contribute to germ cell migration. Together with data from Drosophila (Santos and
      Lehmann, this issue), our results highlight a conserved role for protein
      geranylgeranylation in this context.

PMID- 14960284
TI  - Application and optimization of microarray technologies for human postmortem
      brain studies.
AB  - A number of microarray investigations using human postmortem brain tissue have
      been published recently, exploring a multitude of human brain disorders with the
      aim of unraveling the underlying pathologies. Although the technology is still
      developing and lacks sufficient sensitivity with regard to detecting splice
      variants and low abundance transcripts, microarrays are becoming the prominent
      method for candidate gene screening in complex neuropsychiatric disorders. The
      use of postmortem tissue harbors a variety of potential pitfalls, however, which
      could result in unreliable or, at worst, meaningless results. During the course
      of our large-scale gene expression study on 150 human postmortem brain samples,
      using more than 200 Affymetrix GeneChips, we have identified several aspects
      within microarray experimental procedure that allows for the early identification
      of potentially unreliable samples. The general application of the guidelines and
      technical tips described here increase the efficiency, reliability, and amount of
      data generated by this powerful screening technology while reducing superfluous
      consumption of time and resources.

PMID- 14960283
TI  - The atypical PKC-interacting protein p62 is an important mediator of RANK
      activated osteoclastogenesis.
AB  - The atypical PKCs (aPKCs) have been implicated genetically in at least two
      independent signaling cascades that control NF-kappa B and cell polarity, through
      the interaction with the adapters p62 and Par-6, respectively. P62 binds TRAF6,
      which plays an essential role in osteoclastogenesis and bone remodeling.
      Recently, p62 mutations have been shown to be the cause of the 5q35-linked
      Paget's disease of bone, a genetic disorder characterized by aberrant
      osteoclastic activity. Here we show that p62, like TRAF6, is upregulated during
      RANK-L-induced osteoclastogenesis and that the genetic inactivation of p62 in
      mice leads to impaired osteoclastogenesis in vitro and in vivo, as well as
      inhibition of IKK activation and NF-kappa B nuclear translocation. In addition,
      RANK-L stimulation leads to the inducible formation of a ternary complex
      involving TRAF6, p62, and the aPKCs. These observations demonstrate that p62 is
      an important mediator during osteoclastogenesis and induced bone remodeling.

PMID- 14960285
TI  - Quantitative polymerase chain reaction: validation of microarray results from
      postmortem brain studies.
AB  - Quantitative polymerase chain reaction (Q-PCR) is now considered the "technique
      of choice" for validating gene expression changes identified with ribonucleic
      acid-based expression profiling technologies (especially micro- and macroarray
      techniques). The identification of altered gene expression profiles with
      microarrays is best viewed as the first step in the determination of potential
      disease-associated genes; however, the false-positive rate can be high,
      particularly with small sample sets and in view of the typically small
      differences observed in brain expression studies. Quantitative PCR is a rapid and
      highly sensitive technique for accurate quantification of microarray results;
      however, careful consideration of experimental design, quality of primer/probe
      design, internal standards, and normalization procedures are pivotal,
      particularly when the work involves postmortem tissue.

PMID- 14960286
TI  - Effect of agonal and postmortem factors on gene expression profile: quality
      control in microarray analyses of postmortem human brain.
AB  - There are major concerns that specific agonal conditions, including coma and
      hypoxia, might affect ribonucleic acid (RNA) integrity in postmortem brain
      studies. We report that agonal factors significantly affect RNA integrity and
      have a major impact on gene expression profiles in microarrays. In contrast to
      agonal factors, gender, age, and postmortem factors have less effect on gene
      expression profiles. The Average Correlation Index is proposed as a method for
      evaluating RNA integrity on the basis of similarity of microarray profiles.
      Reducing the variance due to agonal factors is critical in investigating small
      but validated gene expression differences in messenger RNA levels between
      psychiatric patients and control subjects.

PMID- 14960287
TI  - Anatomic evaluation of the orbitofrontal cortex in major depressive disorder.
AB  - BACKGROUND: The orbitofrontal cortex (OFC) plays a major role in neuropsychologic
      functioning including exteroceptive and interoceptive information coding, reward
      guided behavior, impulse control, and mood regulation. This study examined the
      OFC and its subdivisions in patients with MDD and matched healthy control
      subjects. METHODS: Magnetic resonance imaging (MRI) was performed on 31
      unmedicated MDD and 34 control subjects matched for age, gender, and race. Gray
      matter volumes of the OFC and its lateral and medial subdivisions were measured
      blindly. RESULTS: The MDD patients had smaller gray matter volumes in right
      medial [two-way analysis of covariance F(1,60) = 4.285; p =.043] and left lateral
      OFC [F(1,60) = 4.252; p =.044]. Left lateral OFC volume correlated negatively
      with age in patients but not in control subjects. Male, but not female patients
      exhibited smaller left and right medial OFC volumes compared with healthy control
      subjects of the same gender. CONCLUSIONS: These findings suggest that patients
      with MDD have reduced OFC gray matter volumes. Although this reduction might be
      important in understanding the pathophysiology of MDD, its functional and
      psychopathologic consequences are as yet unclear. Future studies examining the
      relationship between specific symptomatic dimensions of MDD and OFC volumes could
      be especially informative.

PMID- 14960288
TI  - Event-related functional magnetic resonance imaging of reward-related brain
      circuitry in children and adolescents.
AB  - BACKGROUND: Functional disturbances in reward-related brain systems are thought
      to play a role in the development of mood, impulse, and substance-abuse
      disorders. Studies in nonhuman primates have identified brain regions, including
      the dorsal/ventral striatum and orbital-frontal cortex, in which neural activity
      is modulated by reward. Recent studies in adults have concurred with these
      findings by observing reward-contingent blood oxygen level-dependent (BOLD)
      responses in these regions during functional magnetic resonance imaging (fMRI)
      paradigms; however, no previous studies indicate whether comparable modulations
      of neural activity exist in the brain reward systems of children and adolescents.
      METHODS: We used event-related fMRI and a behavioral paradigm modeled on previous
      work in adults to study brain responses to monetary gains and losses in
      psychiatrically healthy children and adolescents as part of a program examining
      the neural substrates of anxiety and depression in youth. RESULTS: Regions and
      time-courses of reward-related activity were similar to those observed in adults
      with condition-dependent BOLD changes in the ventral striatum and lateral and
      medial orbital-frontal cortex; specifically, these regions showed larger
      responses to positive than to negative feedback. CONCLUSIONS: These results
      provide further evidence for the value of event-related fMRI in examining reward
      systems of the brain, demonstrate the feasibility of this approach in children
      and adolescents, and establish a baseline from which to understand the
      pathophysiology of reward-related psychiatric disorders in youth.

PMID- 14960289
TI  - Long-term adaptations in glucocorticoid receptor and mineralocorticoid receptor
      mRNA and negative feedback on the hypothalamo-pituitary-adrenal axis following
      neonatal maternal separation.
AB  - BACKGROUND: Maternally separated rats exhibit exaggerated hypothalamic-pituitary
      adrenal responses to an acute stressor but normal diurnal trough functioning. We
      hypothesized that maternally separated rats experience adequate proactive
      glucocorticoid negative feedback but deficient "reactive" negative feedback,
      contributing to prolonged hypothalamic-pituitary-adrenal stress responses.
      METHODS: We measured plasma adrenocorticotropic hormone and corticosterone
      concentrations following an acute stressor or 6 to 8 hours after dexamethasone
      administration in adult rats previously exposed to daily handling-maternal
      separation for 15 minutes (HMS15) or 180 minutes (HMS180) during postnatal days 2
      to 14. We also examined regional mineralocorticoid receptor and glucocorticoid
      receptor messenger RNA density in these two groups. RESULTS: HMS180 rats appeared
      to escape dexamethasone suppression of plasma adrenocorticotropic hormone and
      corticosterone faster than their HMS15 counterparts (p <.01). In situ
      hybridization analysis revealed increased hippocampal mineralocorticoid receptor
      messenger RNA density (p <.05) with decreased cortical (p <.05) and hippocampal
      (p <.05) glucocorticoid receptor messenger RNA density in HMS180 versus HMS15
      animals. CONCLUSIONS: These results are consistent with the hypothesis that in
      rats exposed to moderate neonatal handling-maternal separation, enhanced
      proactive feedback maintains the hypothalamic-pituitary-adrenal axis during the
      diurnal trough, while decreased reactive feedback contributes to prolonged
      responsiveness of the hypothalamic-pituitary-adrenal axis following an acute
      stressor.

PMID- 14960290
TI  - Exposure to postnatal depression predicts elevated cortisol in adolescent
      offspring.
AB  - BACKGROUND: Animal research shows that early adverse experience results in
      altered glucocorticoid levels in adulthood, either raised basal levels or
      accentuated responses to stress. If a similar phenomenon operates in humans, this
      suggests a biological mechanism whereby early adversity might transmit risk for
      major depression, glucocorticoid elevations being associated with the development
      of this disorder. METHODS: We measured salivary cortisol at 8:00 am and 8:00 pm
      over 10 days in 13-year-old adolescents who had (n = 48) or had not (n = 39) been
      exposed to postnatal maternal depression. RESULTS: Maternal postnatal depression
      was associated with higher, more variable morning cortisol in offspring, a
      pattern previously found to predict major depression. CONCLUSIONS: Early adverse
      experiences might alter later steroid levels in humans. Because maternal
      depression confers added risk for depression to children, these alterations might
      provide a link between early events and later psychopathology.

PMID- 14960291
TI  - Mapping brain size and cortical gray matter changes in elderly depression.
AB  - BACKGROUND: In elderly depression, volumetric brain imaging findings suggest
      abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the
      hippocampus. No studies to date have mapped cortical abnormalities over the
      entire brain surface in major depression. Here, we conducted detailed spatial
      analyses of brain size and gray matter within the cortical mantle in elderly
      patients with major depression. METHODS: High-resolution, three-dimensional,
      structural magnetic resonance imaging data and cortical pattern matching methods
      were used in 24 depressed elderly patients and 19 group-matched controls to
      measure local brain size and proportions of gray matter at thousands of
      homologous cortical surface locations. RESULTS: Prominent brain size reductions
      were observed in the depressed subjects in the orbitofrontal cortex bilaterally.
      Cortical gray matter measurements revealed significant gray matter increases in
      the orbitofrontal cortex, adjacent to focal trend level significant decreases of
      gray matter in the same region. Depressed patients also exhibited significant
      gray matter increases in parietal cortices, as well as the left temporal cortex.
      CONCLUSIONS: Complex cortical changes may contribute to the brain size reduction
      of the orbitofrontal cortex and to the gray matter abnormalities detected in
      orbitofrontal cortex and temporoparietal cortices, thereby providing a
      potentially new window into the pathophysiology of elderly depression.

PMID- 14960292
TI  - Clinical characteristics of magnetic resonance imaging-defined subcortical
      ischemic depression.
AB  - BACKGROUND: There is a substantial body of research supporting the vascular
      depression hypothesis of late-life depression. To update this hypothesis so it
      incorporates recent research, we propose that the term subcortical ischemic
      vascular depression may be a more accurate representation of the disease process.
      We sought to investigate this diagnosis as a construct by examining differences
      between depressed subjects with and without magnetic resonance imaging defined
      subcortical ischemic vascular depression. METHODS: This case-control study
      examined 139 depressed elderly subjects. Demographic data, psychiatric, medical,
      and family history, depressive symptomatology, and functional impairment were
      compared between groups dichotomized based on neuroimaging findings. RESULTS:
      Seventy-five (54%) of the subjects met neuroimaging criteria for subcortical
      ischemic vascular depression. Age was most strongly associated with increased
      prevalence of subcortical ischemic vascular depression. Lassitude and a history
      of hypertension were also positively associated with the diagnosis; a family
      history of mental illness and loss of libido were negatively associated with the
      diagnosis. CONCLUSIONS: These data support that subcortical ischemic vascular
      depression may be a specific syndrome from other types of late-life depression.
      Further research is needed to further characterize this disorder, particularly in
      regards to cognitive function and treatment implications.

PMID- 14960293
TI  - Repetitive transcranial magnetic stimulation as treatment of poststroke
      depression: a preliminary study.
AB  - BACKGROUND: Depression has a significant impact on poststroke recovery and
      mortality. There are a proportion of patients with poststroke depression (PSD)
      who do not respond to antidepressants. Repetitive Transcranial Magnetic
      Stimulation (rTMS) might be a safe and effective alternative in these refractory
      cases. METHODS: We conducted a randomized, parallel, double-blind study of active
      versus sham left prefrontal rTMS in patients with refractory PSD. After
      discontinuing antidepressants, patients were randomly assigned to receive 10
      sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds
      duration) or sham left prefrontal rTMS. Efficacy measures included HAM-D scores,
      response and remission rates. Patients completed a neuropsychological battery at
      baseline and after completing the protocol. RESULTS: When compared with sham
      stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal
      cortex were associated with a significant reduction of depressive symptoms. This
      reduction was not influenced by patient's age, type or location of stroke, volume
      of left frontal leukoaraiosis or by the distance of the stimulating coil to the
      prefrontal cortex. However, there was a significant positive correlation between
      the percentage of reduction of Ham-D scores and frontal gray and white matter
      volumes. There were no significant changes in cognitive functioning between the
      active and the sham stimulation groups. In addition, there were few and mild
      adverse effects that were equally distributed among groups. CONCLUSIONS: Taken
      together, these preliminary findings suggest that rTMS may be an effective and
      safe treatment alternative for patients with refractory depression and stroke.

PMID- 14960294
TI  - Lack of efficacy of estradiol for depression in postmenopausal women: a
      randomized, controlled trial.
AB  - BACKGROUND: Estrogen has been considered as a potential antidepressant in
      postmenopausal women. Our goal was to study whether estrogen therapy is effective
      in treating depressive disorders in older postmenopausal women and to determine
      whether progestins are associated with a deterioration of mood. METHODS: After 2
      weeks of single-blind placebo treatment in 87 patients, 57 were randomly assigned
      to receive 8 weeks of treatment with estradiol (.1 mg/day; n = 31) or placebo (n
      = 26). All patients were then treated with medroxyprogesterone 10 mg/day for 2
      weeks combined with the study patch. Depressive symptoms were rated with the 21
      item Hamilton Depression and Center for Epidemiologic Studies Depression scales.
      RESULTS: A clinically significant antidepressant effect of estradiol was excluded
      after 8 weeks of estradiol treatment. The estradiol group and placebo group
      improved in depressive symptoms at a similar rate based on the Hamilton
      Depression Scale (40% decreases in depression for estradiol vs. 44% for placebo).
      No significant increase in depressive symptoms was demonstrated with the use of
      progestins; however, positive affect decreased slightly with the use of combined
      estradiol-medroxyprogesterone compared with medroxyprogesterone alone (5.8%, p
      =.027). CONCLUSIONS: Estradiol cannot be considered as an effective treatment in
      postmenopausal women with mild to moderate depression.

PMID- 14960295
TI  - Association between the HOXA1 A218G polymorphism and increased head circumference
      in patients with autism.
AB  - BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial
      morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously
      found associated with autism. METHODS: We performed case-control and family-based
      association analyses, contrasting 127 autistic patients with 174 ethnically
      matched controls, and assessing for allelic transmission disequilibrium in 189
      complete trios. RESULTS: A, and not G, alleles were associated with autism using
      both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes
      and alleles, respectively), and family-based (transmission/disequilibrium test
      chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31
      patients carrying one or two copies of the G allele displayed significantly
      larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically
      reduced interindividual variability (p <.0001), compared with 166 patients
      carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains
      approximately 5% of the variance in the head circumference of autistic patients
      and represents to our knowledge the first known gene variant providing sizable
      contributions to cranial morphology. The disease specificity of this finding is
      currently being investigated. Nonreplications in genetic linkage/association
      studies could partly stem from the dyshomogeneous distribution of an
      endophenotype morphologically defined by cranial circumference.

PMID- 14960296
TI  - Electroconvulsive seizures induce endothelial cell proliferation in adult rat
      hippocampus.
AB  - BACKGROUND: Electroconvulsive seizures, an animal model for electroconvulsive
      treatment, induce a strong increase in neurogenesis in the dentate gyrus of adult
      rats. Hippocampal neurogenesis has previously been described as occurring in an
      angiogenic niche. This study examines the effect of electroconvulsive seizures on
      proliferation of vascular cells in rat hippocampus. METHODS: Rats were injected
      with bromodeoxyuridine to label proliferating cells in the dentate gyrus after
      single/multiple electroconvulsive seizures in a dose-response study and at
      various time points after single electroconvulsive seizures in a time-course
      study. RESULTS: A dose-response effect on the number of bromodeoxyuridine-labeled
      endothelial cells located in the granule cell layer, hilus, and molecular layer
      was noted, as was the case with the number of neural precursors in the
      subgranular zone. The time-course study revealed that endothelial cell and neural
      precursor proliferation occurred in concert in response to a single
      electroconvulsive seizure. CONCLUSIONS: Our data suggest that in response to
      electroconvulsive seizures, endothelial cell and neural proliferation is
      coregulated. The increase in endothelial cell proliferation may act to support
      the increased neural proliferation and neuronal activity or vice versa, possibly
      leading to structural changes within the hippocampus of importance for the
      antidepressant effect of electroconvulsive seizures.

PMID- 14960297
TI  - Robust and tissue-specific expression of TPH2 versus TPH1 in rat raphe and pineal
      gland.
AB  - BACKGROUND: Regulation of raphe serotonergic cells is fundamental to the
      prevailing hypothesis of major depression pathophysiology. Tryptophan hydroxylase
      (TPH) is the rate-limiting enzyme in serotonin biosynthesis, but brainstem TPH
      mRNA expression has been difficult to measure and study. Recently, a novel
      paralog of TPH, TPH2 (or neuronal TPH), was described, but its anatomic
      expression is unknown. METHODS: In situ hybridization histochemical survey was
      conducted across Sprague-Dawley rat brain for TPH1 and TPH2 mRNA.
      Semiquantitative techniques were used to estimate relative mRNA levels in
      individual cells. RESULTS: Almost exclusively, TPH2 mRNA is expressed in raphe,
      in a pattern overlapping the histologically defined raphe nuclei. In sharp
      contrast, TPH1 (the previously known TPH) is expressed predominantly in pineal
      gland. There is no appreciable overlap in the expression of these paralogs. The
      level of TPH2 mRNA expression in individual raphe cells is approximately 2.5-fold
      greater than the level of TPH1 expression in pinealocytes. CONCLUSIONS: TPH2 mRNA
      has an anatomic expression pattern consistent with brainstem raphe nuclei and is
      likely to be the gene giving rise to the majority of TPH activity in these cells.
      The robust expression of TPH2 in brainstem should facilitate studies on the
      transcriptional regulation of raphe serotonin biosynthesis.

PMID- 14960298
TI  - High nitric oxide production in autistic disorder: a possible role for interferon
      gamma.
AB  - BACKGROUND: Neuroimmune regulation abnormalities have been implicated in the
      pathophysiology of autistic disorder. Nitric oxide (NO) is involved in immune
      reactivity and is known to affect brain neurodevelopmental processes. Recent
      evidence indicates that NO, and cytokines involved in NO production, may be high
      in children with autism. The purpose of this study was to verify that plasma NO
      is high in children with autism and determine whether this elevation is related
      to plasma levels of cytokines involved in NO production. METHODS: The metabolites
      of NO, nitrite, and nitrate (NOx), along with the cytokines interferon-gamma (IFN
      gamma), tumor necrosis factor-alpha, and interleukin-1beta, were measured in
      plasma of 29 children with autism (mean age +/- SD = 6.1 +/- 2.8 years) and 27
      age- and gender-matched healthy comparison subjects using commercially available
      assay kits. RESULTS: Plasma levels of NOx were significantly higher in the
      autistic subjects (p =.006); plasma levels of the cytokines did not differ
      between groups. NOx and IFN-gamma levels were positively correlated in the
      autistic subjects (r =.51; p =.005). CONCLUSIONS: These results confirm that
      plasma NO is high in some children with autism and suggest that this elevation
      may be related to IFN-gamma activity.

PMID- 14960299
TI  - Emerging neuroskeletal signalling pathways: a review.
AB  - Recent work has demonstrated that neurotransmitters, signalling molecules
      primarily associated with the nervous system, can have profound effects on the
      skeleton. Bone cells express a broad range of neurotransmitter receptors and
      transporters, and respond to receptor activation by initiating diverse
      intracellular signalling pathways, which modulate cellular function. Evidence of
      neuronal innervation in skeletal tissues, neurotransmitter release directly from
      bone cells and functional effects of pharmacological manipulation support the
      existence of a complex and functionally significant neurotransmitter-mediated
      signalling network in bone. This review aims to concisely summarise our current
      understanding of how neurotransmitters affect the skeletal system, focusing on
      their origin, cellular targets and functional effects in bone.

PMID- 14960300
TI  - Identification of a novel protein complex containing annexin A4, rabphilin and
      synaptotagmin.
AB  - Rabphilin is a synaptic vesicle-associated protein proposed to play a role in
      regulating neurotransmitter release. Here we report the isolation and
      identification of a novel protein complex containing rabphilin, annexin A4 and
      synaptotagmin 1. We show that the rabphilin C2B domain interacts directly with
      the N-terminus of annexin A4 and mediates the co-complexing of these two proteins
      in PC12 cells. Analyzing the cellular localisation of these co-complexing
      proteins we find that annexin A4 is located on synaptic membranes and co
      localises with rabphilin at the plasma membrane in PC12 cells. Given that
      rabphilin and synaptotagmin are synaptic vesicle proteins involved in
      neurotransmitter release, the identification of this complex suggests that
      annexin A4 may play a role in synaptic exocytosis.

PMID- 14960301
TI  - Absolute expression values for mouse transcripts: re-annotation of the READ
      expression database by the use of CAGE and EST sequence tags.
AB  - The RIKEN expression array database (READ) provides comprehensive gene expression
      data for the mouse, which were obtained as relative values from microarray double
      staining experiments with E17.5 mRNA as common reference. To assign absolute
      expression values for mouse transcripts within READ, we applied the E17.5
      reference sample to CAGE (cap analysis of gene expression) and expressed sequence
      tag (EST) high-throughput tag sequencing. Newly assigned values within the READ
      database were validated by comparison to expression data from serial analysis of
      gene expression, CAGE and EST experiments. These experiments confirmed the great
      significance of the absolute expression values within the improved READ database.
      The new Absolute READ database on absolute expression data is available under.

PMID- 14960302
TI  - Class III alcohol dehydrogenase: consistent pattern complemented with the
      mushroom enzyme.
AB  - Mushroom alcohol dehydrogenase (ADH) from Agaricus bisporus (common mushroom,
      champignon) was purified to apparent homogeneity. One set of ADH isozymes was
      found, with specificity against formaldehyde/glutathione. It had two highly
      similar subunits arranged in a three-member isozyme set of dimers with
      indistinguishable activity. Determination of the primary structure by a
      combination of chemical, mass spectrometric and cDNA sequence analyses,
      correlated with molecular modeling towards human ADHs, showed that the active
      site residues are of class III ADH type, and that the subunit differences affect
      other residues. Class I and III forms of ADHs characterized define conserved
      substrate-binding residues (three and eight, respectively) useful for recognition
      of these enzymes in any organism.

PMID- 14960304
TI  - The C-terminal region as a modulator of rNa(v)1.7 and rNa(v)1.8 expression
      levels.
AB  - Mammalian cells poorly express rNa(v)1.8 channels. In contrast, rNa(v)1.7 dorsal
      root ganglion channels have 90-fold higher peak Na(+) current densities. We
      investigated the role of rNa(v)1.7 and rNa(v)1.8 carboxy-termini in modulating
      the expression of rNa(v)1.7 and rNa(v)1.8 channels in tsA201 cells. Mutations in
      the ubiquitination site of the C-terminus did not improve rNa(v)1.8 current
      levels. However, rNa(v)1.8 chimeras containing the entire or the proximal portion
      of the rNa(v)1.7 C-terminus expressed 3.2-fold and 4.8-fold higher peak current
      densities, respectively, than parent rNa(v)1.8 channels. We conclude that the two
      Na(+) channels may have different endoplasmic reticulum processing signals.

PMID- 14960303
TI  - ERK-1/2 activity is required for efficient RSV infection.
AB  - Respiratory syncytial virus (RSV) infection up-regulates the expression of genes
      encoding proinflammatory mediators in bronchial epithelial cells. However, the
      specific signaling events immediately following RSV exposure are poorly
      understood. Herein, we report that RSV attachment to A549 cells activates both
      ERK-1 and ERK-2 pathways within 5 min. Inhibition of ERK pathways significantly
      decreases RSV infection of these cells compared to controls. These results
      demonstrate that the activation of the ERK-1/2 is required in RSV-induced early
      gene expression.

PMID- 14960305
TI  - Volume-regulated Cl- channels in human pleural mesothelioma cells.
AB  - Anion channels in human mesothelial and mesothelioma cell lines were
      characterized by patch-clamp and biomolecular approaches. We found an outwardly
      rectifying anionic current which was inactivated at positive voltages and
      inhibited by extracellular adenosine 5'-triphosphate (ATP). Mesothelial and
      mesothelioma cells behaved differently concerning current inactivation
      properties. Inactivation is more pronounced and has a steeper onset in
      mesothelial cells. Different reversal potentials, in asymmetrical Cl(-)
      solutions, that could be attributed to a different selectivity of the channel,
      have been observed in the two cell lines. Mesothelioma cell single-channel
      analysis indicates that the number of the same active anion channel (3-4 pS)
      increased under hypoosmotic conditions. Immunocytochemistry experiments showed
      the presence of ICln protein in the cytosol and in the plasma membrane. Western
      blot analysis revealed an increase of ICln in the membrane under hypotonic
      conditions, an event possibly related to the activation of Cl(-) channels.

PMID- 14960306
TI  - vAL-1, a novel polysaccharide lyase encoded by chlorovirus CVK2.
AB  - Cell wall materials isolated from Chlorella cells were degraded by the
      polysaccharide-degrading enzyme vAL-1 encoded by chlorovirus CVK2. Matrix
      assisted laser desorption/ionization time-of-flight mass spectrometric analyses
      of the degradation products (oligosaccharides) revealed major oligosaccharides
      contain unsaturated GlcA at the reducing terminus, and a side chain attached at
      C2 or C3 of GlcA(C4?C5), which mainly consisted of Ara, GlcNAc and Gal. The
      results indicated that vAL-1 is a novel polysaccharide lyase, cleaving chains of
      beta- or alpha-1,4-linked GlcAs. The unique structures of Chlorella cell wall
      were also revealed. Studies on the complicated structures of naturally occurring
      polysaccharides will be greatly facilitated by using vAL-1 as a tool in
      structural analysis.

PMID- 14960308
TI  - A role for expansins in dehydration and rehydration of the resurrection plant
      Craterostigma plantagineum.
AB  - Craterostigma plantagineum is one of the few higher plants capable of surviving
      desiccation throughout its vegetative tissues. Water loss results in cell
      shrinkage and a commensurate folding of the cell wall indicating an unusual
      degree of wall flexibility. We show that wall extensibility undergoes a marked
      increase during dehydration and rehydration. Similar increases were observed in
      the activity of expansins in cell walls during these processes suggesting a role
      for these proteins in increasing wall flexibility. Three alpha-expansin cDNAs
      were cloned from dehydrating leaves and transcript levels for one correlated
      closely with the observed changes in expansin activity during the dehydration and
      rehydration of leaves.

PMID- 14960307
TI  - The mouse FKBP23 binds to BiP in ER and the binding of C-terminal domain is
      interrelated with Ca2+ concentration.
AB  - FK506 binding protein 23 from mouse (mFKBP23) is a peptidyl-prolyl cis-trans
      isomerase (PPIase) from the endoplasmic reticulum (ER), which consists of an N
      terminal PPIase domain and a C-terminal domain with Ca(2+) binding sites. The
      assay of adsorption from ER extract with glutathione S-transferase-mFKBP23
      attached to glutathione-Sepharose 4B shows that mFKBP23 binds to mouse
      immunoglobulin binding protein (mBiP). The same assay with the recombinant
      proteins of the N- and C-termini of mFKBP23 shows that the binding of the C
      terminus is Ca(2+)-dependent and the switch point is between 2 and 3 mM. By high
      concentration of Ca(2+) this binding cannot be detected. Furthermore, the Ca(2+)
      regulated binding of mFKBP23 and mBiP in ER can be detected by means of co
      immunoprecipitation.

PMID- 14960309
TI  - Cell-free production of active E. coli thioredoxin reductase and glutathione
      reductase.
AB  - Escherichia coli thioredoxin reductase (TR) and glutathione reductase (GR) are
      dimeric proteins that require a flavin adenine dinucleotide (FAD) cofactor for
      activity. A cell-free protein synthesis (CFPS) reaction supplemented with FAD was
      used to produce TR at 760 microg/ml with 89% of the protein being soluble. GR
      accumulated to 521 microg/ml in a cell-free reaction with 71% solubility. The TR
      produced was fully active with a specific activity of 1390 min(-1). The GR had a
      specific activity of 139 U/mg, which is significantly more active than reported
      for GR purified from cells. The specific activity for both TR and GR decreased
      without FAD supplementation. This research demonstrates that CFPS can be used to
      produce enzymes that are multimeric and require a cofactor.

PMID- 14960310
TI  - Interleukin-12 secreted by mature dendritic cells mediates activation of NK cell
      function.
AB  - Dendritic cells (DCs) are known to modulate immune response by activating
      effector cells of both the innate and the adaptive immune system. In the present
      study, we demonstrate that co-culture of DCs with paraformaldehyde-fixed tumor
      cells augments the secretion of interleukin (IL)-12 by DCs and these activated
      DCs upon co-culture with naive NK cells enhance the cytolytic activity of NK
      cells against NK-sensitive target YAC-1. Similarly, DCs isolated from tumor
      bearing animals also activated NK cells in vitro. For efficient activation of NK
      cells, the ratio of activated DCs to NK cells is crucial. Addition of anti-IL-12
      antibody to the culture system completely abolished activation of NK cells by
      DCs, suggesting that IL-12 secreted by DCs is an essential factor in NK cell
      activation. Adoptive transfer of DCs isolated from tumor-bearing animals into
      normal rats also induced activation of NK cells in normal animals.

PMID- 14960311
TI  - The giant protein HERC1 is recruited to aluminum fluoride-induced actin-rich
      surface protrusions in HeLa cells.
AB  - HERC1 is a very large protein involved in membrane traffic through both its
      ability to bind clathrin and its guanine nucleotide exchange factor (GEF)
      activity over ARF and Rab family GTPases. Herein, we show that HERC1 is recruited
      onto actin-rich surface protrusions in ARF6-transfected HeLa cells upon aluminum
      fluoride (AlF(4)(-)) treatment. Moreover, the fact that HERC1 overexpression does
      not stimulate protrusion formation in the absence of AlF(4)(-), in conditions
      where ARNO does, indicates that HERC1 is not acting as an ARF6-GEF in this
      system, but that instead its recruitment takes place downstream of ARF6
      activation. Finally, we suggest a phosphoinositide-binding mechanism whereby
      HERC1 may translocate to these protrusions.

PMID- 14960312
TI  - Characterization of altered regulation variants of dinitrogenase reductase
      activating glycohydrolase from Rhodospirillum rubrum.
AB  - In Rhodospirillum rubrum, nitrogenase activity is subject to posttranslational
      regulation through the adenosine diphosphate (ADP)-ribosylation of dinitrogenase
      reductase by dinitrogenase reductase ADP-ribosyltransferase (DRAT) and
      dinitrogenase reductase-activating glycohydrolase (DRAG). To study the
      posttranslational regulation of DRAG, its gene was mutagenized and colonies
      screened for altered DRAG regulation. Three different mutants were found and the
      DRAG variants displayed different biochemical properties including an altered
      affinity for divalent metal ions. Taken together, the results suggest that the
      site involved in regulation is physically near the metal binding site of DRAG.

PMID- 14960313
TI  - The functional interaction between HMGA1 and the estrogen receptor requires
      either the N- or the C-terminal domain of the receptor.
AB  - We have previously shown that HMGA1 enhances the transcriptional activity of
      promoters containing the estrogen response element (ERE) and increases binding of
      the estrogen receptor (ER) to ERE. Herein, we have assessed the transcriptional
      activity and ERE-binding ability of deleted ER fragments in absence or in
      presence of HMGA1. The HMGA1 protein stimulated binding and transcriptional
      activity by a factor of about 2-fold compared to the wild-type ER and both the N-
      and C-terminal ER deleted domains, but had no effect when both domains were
      deleted. These data show that HMGA1 cooperates with either the N- or the C
      terminal transcriptional activation domain of the ER.

PMID- 14960314
TI  - Interactions of acid sphingomyelinase and lipid bilayers in the presence of the
      tricyclic antidepressant desipramine.
AB  - The tricyclic antidepressant desipramine causes a decrease in cellular acid
      sphingomyelinase (A-SMase, EC 3.1.4.12) activity when added to culture medium of
      human fibroblasts. This effect can be prevented by incubation of the cells with
      the protease inhibitor leupeptin, which suggests that desipramine induces
      proteolytic degradation of the lysosomal enzyme. By using surface plasmon
      resonance (SPR, Biacore) we were able to monitor the interactions of A-SMase and
      substrate-containing lipid bilayers immobilized on the surface of a Pioneer trade
      mark L1 sensor chip. SPR binding curves show that the enzyme hardly dissociates
      from the lipid surface at acidic pH values. On the other hand, a drop in binding
      signals (resonance units, RU) of approximately 50% occurred after injection of 20
      mM desipramine. Our findings indicate that desipramine interferes with the
      binding of A-SMase to the lipid bilayers and thereby displaces the enzyme from
      its membrane-bound substrate. The application of control substances suggests a
      key role for the cationic moiety of desipramine. We hypothesize that the
      displacement of the glycoprotein A-SMase from the inner membranes of late
      endosomes and lysosomes by desipramine renders it susceptible to proteolytic
      cleavage by lysosomal proteases.

PMID- 14960315
TI  - Characterization of CXIP4, a novel Arabidopsis protein that activates the H+/Ca2+
      antiporter, CAX1.
AB  - Precise regulation of calcium transporters is essential for modulating the Ca2+
      signaling network that is involved in the growth and adaptation of all organisms.
      The Arabidopsis H+/Ca2+ antiporter, CAX1, is a high capacity and low affinity
      Ca2+ transporter and several CAX1-like transporters are found in Arabidopsis.
      When heterologously expressed in yeast, CAX1 is unable to suppress the Ca2+
      hypersensitivity of yeast vacuolar Ca2+ transporter mutants due to an N-terminal
      autoinhibition mechanism that prevents Ca2+ transport. Using a yeast screen, we
      have identified CAX nteracting Protein 4 (CXIP4) that activated full-length CAX1,
      but not full-length CAX2, CAX3 or CAX4. CXIP4 encodes a novel plant protein with
      no bacterial, fungal, animal, or mammalian homologs. Expression of a GFP-CXIP4
      fusion in yeast and plant cells suggests that CXIP4 is targeted predominantly to
      the nucleus. Using a yeast growth assay, CXIP4 activated a chimeric CAX construct
      that contained specific portions of the N-terminus of CAX1. Together with other
      recent studies, these results suggest that CAX1 is regulated by several signaling
      molecules that converge on the N-terminus of CAX1 to regulate H+/Ca2+ antiport.

PMID- 14960316
TI  - Autocrine release of TGF-beta by portal fibroblasts regulates cell growth.
AB  - Portal fibroblasts (PF) are a newly isolated population of fibrogenic cells in
      the liver postulated to play a significant role in early biliary fibrosis.
      Because transforming growth factor-beta (TGF)-beta is a key growth factor in
      fibrosis, we characterized the response of PF to TGF-beta. We demonstrate that PF
      produce significant amounts of TGF-beta2 and, unlike activated hepatic stellate
      cells (HSC), express all three TGF-beta receptors and are growth inhibited by TGF
      beta1 and TGF-beta2. Fibroblast growth factor (FGF)-2, but not platelet derived
      growth factor (PDGF), causes PF proliferation. These data suggest a mechanism
      whereby HSC eclipse PF as the dominant myofibroblast population in biliary
      fibrosis.

PMID- 14960317
TI  - Expression regulation of the yeast PDR5 ATP-binding cassette (ABC) transporter
      suggests a role in cellular detoxification during the exponential growth phase.
AB  - The yeast ATP-binding cassette transporter Pdr5p mediates pleiotropic drug
      resistance (PDR) by effluxing a variety of xenobiotics. Immunoblotting
      demonstrates that Pdr5p levels are high in the logarithmic growth phase, while
      its levels decrease sharply when cells exit exponential growth. Here, we show
      that PDR5 promoter activity is dramatically reduced when cells stop growing due
      to a limitation of glucose or nitrogen or when they approach stationary phase.
      Interestingly, Pdr3p, a major transcriptional regulator of PDR5, shows the same
      regulatory pattern. Feeding glucose to starved cells rapidly re-induces both PDR5
      and PDR3 transcription. Importantly, diminished Pdr5p levels, as present after
      starvation, are rapidly restored in response to xenobiotic challenges that
      activate the transcription factors Pdr1p and Pdr3p. Our data indicate a role for
      yeast Pdr5p in cellular detoxification during exponential growth.

PMID- 14960318
TI  - Involvement of the cGMP signalling pathway in the regulation of viability in
      insulin-secreting BRIN-BD11 cells.
AB  - We have evaluated the hypothesis that cGMP may serve as an intracellular
      messenger regulating the viability of pancreatic beta-cells. A direct activator
      of soluble guanylyl cyclase, YC-1, caused a time- and dose-dependent loss of
      viability in clonal BRIN-BD11 beta-cells. This was accompanied by a rise in cGMP
      and was antagonised by Rp-8-pCPT-cGMPS, a selective inhibitor of protein kinase G
      (PKG). Reverse transcription polymerase chain reaction analysis confirmed that
      BRIN-BD11 cells (and human islets) express all three known isoforms of PKG (PKG
      Ialpha, -Ibeta and II). Cell death induced by YC-1 was not sensitive to cell
      permeable caspase inhibitors and was not accompanied by oligonucleosomal DNA
      fragmentation. The response was, however, inhibited by actinomycin D, suggesting
      that a transcription-dependent pathway of programmed cell death is involved in
      the actions of cGMP.

PMID- 14960319
TI  - Dietary fish oil up-regulates cholesterol 7alpha-hydroxylase mRNA in mouse liver
      leading to an increase in bile acid and cholesterol excretion.
AB  - To investigate the molecular events controlling reverse cholesterol transport, we
      compared gene expression of normal mouse liver to that of mice fed a long chain
      (LC) omega-3 fatty acid-enriched diet. Using cDNA microarrays, we assessed
      expression levels of 1176 genes, and we found that D-site binding protein (DBP)
      was three-fold increased in mice on a LC omega-3 fatty acid-rich diet compared to
      controls. DBP is known to increase transcriptional level of cholesterol 7alpha
      hydroxylase (C7alpha), the rate-limiting enzyme for bile acid production and
      cholesterol excretion, and we found that C7alpha mRNA was also up-regulated by LC
      omega-3 fatty acids. Moreover, liver X receptor-alpha, another transcription
      factor up-regulating C7alpha, was three- to four-fold increased in liver of
      treated mice. On the other hand, we demonstrated that bile acid and cholesterol
      excretion were two-fold increased. These results show that LC omega-3 fatty acids
      control cholesterol metabolism in mice at a new endpoint.

PMID- 14960320
TI  - Functional proteomics of circadian expressed proteins from Chlamydomonas
      reinhardtii.
AB  - In this study, functional proteomics was successfully applied for the
      characterization of circadian expressed, basic proteins. For this purpose, we
      have chosen the green model alga Chlamydomonas reinhardtii since its entire
      nuclear genome is available and it is ideally suited for biochemical enrichment
      procedures. Proteins from cells harvested during subjective day and night were
      heparin affinity purified. They were separated by two-dimensional gel
      electrophoresis suited for basic proteins and analyzed after tryptic digestion by
      electrospray ionization mass spectrometry. We can show for the first time that
      the expressions of a protein disulfide isomerase-like protein and a
      tetratricopeptide repeat protein change in a circadian manner. Interestingly,
      both proteins are known to be interaction partners in multiprotein complexes
      including RNA binding proteins.

PMID- 14960321
TI  - Characterization of CJ1293, a new UDP-GlcNAc C6 dehydratase from Campylobacter
      jejuni.
AB  - Campylobacter jejuni encodes numerous sugar-nucleotide-modifying enzymes
      potentially involved in the biosynthesis of surface carbohydrates. One of them,
      CJ1293, is involved in flagellin glycosylation but its biochemical activity
      remains unknown. Using over-expressed and purified protein, we demonstrate that
      CJ1293 has UDP-GlcNAc-specific C(6) dehydratase activity. Catalysis occurs
      without addition of cofactor, suggesting internal recycling of NAD(P)(+). The
      K(m) for UDP-GlcNAc of 50 microM indicates that CJ1293 has higher affinity for
      its substrate than previously characterized homologues. Based on enzymatic data,
      we propose that CJ1293 catalyzes the first step in the biosynthesis of
      bacillosamine, a sugar found in C. jejuni's protein glycosylation motifs.

PMID- 14960322
TI  - LY294002 inhibits monocyte chemoattractant protein-1 expression through a
      phosphatidylinositol 3-kinase-independent mechanism.
AB  - The effects of LY294002 (LY29) and wortmannin (WM), inhibitors of
      phosphatidylinositol 3-kinase (PI3K), on monocyte chemoattractant protein-1 (MCP
      1) expression by human umbilical vein endothelial cells were investigated.
      Complete inhibition of interleukin (IL)-1beta-induced Akt phosphorylation
      occurred at 50 microM LY29 or 100 nM WM. At these concentrations, LY29, but not
      WM, significantly inhibited constitutive and IL-1beta-induced MCP-1 expression at
      both protein and mRNA levels. LY303511 (LY30), an inactive analogue of LY29, also
      inhibited MCP-1 expression. LY29 and LY30 inhibited activation of nuclear factor
      kappaB (NF-kappaB). These results suggest that LY29 inhibits MCP-1 expression at
      least in part via suppression of NF-kappaB, independent of PI3K, and the
      structure of LY29 and LY30 may be a novel template for development of new anti
      inflammatory drugs.

PMID- 14960323
TI  - Structural features of transmembrane helices.
AB  - A total of 160 transmembrane helices of 15 non-homologous high-resolution X-ray
      protein structures have been analyzed in respect of their structural features.
      The dihedral angles and hydrogen bonds of the helical sections that span the
      hydrophobic interior of the lipid bilayer have been investigated. The
      Ramachandran plot of protein channels and solute transporters exhibit a
      significant shift Delta (phi- and psi-angles) of Delta mean (+4.5 degrees and 
      5.4 degrees ), compared to a reference group of 151 alpha-helices of the same
      average length derived from water-soluble globular proteins. At the C-termini of
      transmembrane helices structural motifs equivalent to the Gly-caps of helices in
      globular proteins have been found, with two third of the transmembrane Gly-caps
      taking up a primary structure that is typically not found at helix termini
      exposed to a polar solvent. The structural particularities reported here are
      relevant for the three-dimensional modelling of membrane protein structures.

PMID- 14960324
TI  - p53 mediates density-dependent growth arrest.
AB  - While the stress-response-associated importance of the p53 tumor suppressor is
      well established, recent studies have also linked p53 with several basic
      parameters in the normal behavior of cells. Here, we present evidence that basal
      p53 expression in WI38 human embryonic lung fibroblasts restricts growth rate and
      mediates density-dependent inhibition of growth and the associated G1 phase
      arrest of the cell cycle by affecting the density-dependent regulation of
      p16/INK4a. Additionally, we show that prolonged culturing of hTert-immortalized
      WI38 cells leads to a loss of density-dependent growth inhibition that correlates
      with p27/KIP deregulation as well as the previously shown INK4a locus silencing,
      and to an onset of contact-induced, p53-dependent cell death.

PMID- 14960325
TI  - Transient expression analysis of the mouse ornithine decarboxylase antizyme
      haploid-specific promoter using in vivo electroporation.
AB  - The testicular isoform of the ornithine decarboxylase antizyme (OAZt) gene is
      expressed exclusively in the haploid spermatids of mice. The 357-bp region, which
      includes a TATA-less promoter and an untranslated region, is sufficient for OAZt
      gene expression in the spermatids of transgenic mice. In this study, in vivo
      transient transfection to living mouse testes was used to define the
      transcriptional regulatory elements of the OAZt gene promoter. We found that the
      10-bp element that contains an initiator (Inr) plays a central role as the core
      promoter, in combination with a downstream element, while two cyclic adenosine
      monophosphate-responsive element (CRE)-like sites in the upstream region also
      contribute to promoter activity. The electrophoretic mobility shift assay showed
      binding of the testis-specific factors to these elements. Our results show that
      the in vivo DNA transfer technique enables detailed analysis of haploid germ cell
      specific gene regulation in mice.

PMID- 14960326
TI  - Coactivator ASC-2 mediates heat shock factor 1-mediated transactivation dependent
      on heat shock.
AB  - Upon exposure to elevated temperatures, mammalian cells increase the expression
      of the heat shock proteins (HSP) through activation of the heat shock factor 1
      (HSF1). Since most transcription factors require coactivators for efficient
      transcriptional activity, we tried to identify the coactivator(s) that interacts
      with and modulates the activities of HSF1. In vitro glutathione S-transferase
      (GST) pull-down assay revealed that HSF1 strongly interacts with activating
      signal cointegrator (ASC)-2 and weakly with cyclic adenosine monophosphate
      responsive element binding protein (CBP). We also show that cotransfection of ASC
      2, but not CBP, potentiates HSF1-mediated transactivation based on its cognate
      element (heat shock element, HSE) linked to luciferase reporter. The molecular
      interaction of HSF1 and ASC-2 was stimulated by heat shock in cells and the
      overexpression of HSF1-interacting domain of ASC-2 inhibited the specific induced
      protein association and HSF1-mediated transactivation. Taking these results
      together, we suggest that ASC-2 in a novel coactivator for HSF1 and heat shock
      stress may contribute the strong active transcription complex through sequential
      recruitment of HSF1 and ASC-2.

PMID- 14960327
TI  - Defining the p53 DNA-binding domain/Bcl-x(L)-binding interface using NMR.
AB  - p53 exerts its tumor suppressor activity through both transcription-dependent and
      transcription-independent processes. Although the transcription-dependent
      activity of p53 has been extensively studied, the mechanism for transcription
      independent p53-mediated tumor suppression is less well known. Recently, it was
      reported that p53 can directly induce mitochondrial permeabilization and promote
      apoptosis. This occurs through complexation of the DNA-binding region of p53 with
      the anti-apoptotic proteins Bcl-x(L) and Bcl-2 (Mihara, M. et al. (2003) Mol.
      Cell 11, 577-590). Using nuclear magnetic resonance (NMR) spectroscopy we show
      that the interaction surface on p53 involves the same region that is used by the
      protein to contact DNA. The p53-binding site on Bcl-x(L) consists of the carboxy
      terminus of the first alpha-helix, the loop between alpha3 and alpha4, and the
      loop between alpha5 and alpha6 of Bcl-x(L). Furthermore, the interaction of p53
      with Bcl-x(L) is blocked by the binding of a 25-residue peptide derived from the
      BH3 region of the pro-apoptotic protein referred to as Bad.

PMID- 14960328
TI  - Endogenous calmodulin interacts with the epidermal growth factor receptor in
      living cells.
AB  - We have previously shown that exogenous calmodulin (CaM) binds to the epidermal
      growth factor receptor (EGFR) at its cytosolic juxtamembrane region inhibiting
      its tyrosine kinase activity. We demonstrate in this report that endogenous CaM
      binds to EGFR in intact cells as CaM co-immunoprecipitates with EGF-activated and
      non-activated receptors. We also show in living cells that cell-permeable CaM
      inhibitors prevent the full transphosphorylation of wild type EGFR but not the
      transphosphorylation of an insertional EGFR mutant in which the CaM-binding
      domain was divided into two parts. Overall these results suggest that CaM
      interacts with EGFR in vivo.

PMID- 14960329
TI  - Low temperature or GroEL/ES overproduction permits growth of Escherichia coli
      cells lacking trigger factor and DnaK.
AB  - Escherichia coli trigger factor (TF) and DnaK cooperate in the folding of newly
      synthesized proteins. The combined deletion of the TF-encoding tig gene and the
      dnaK gene causes protein aggregation and synthetic lethality at 30 degrees C.
      Here we show that the synthetic lethality of DeltatigDeltadnaK52 cells is
      abrogated either by growth below 30 degrees C or by overproduction of
      GroEL/GroES. At 23 degrees C DeltatigDeltadnaK52 cells were viable and showed
      only minor protein aggregation. Overproduction of GroEL/GroES, but not of other
      chaperones, restored growth of DeltatigDeltadnaK52 cells at 30 degrees C and
      suppressed protein aggregation including proteins >/=60 kDa, which normally
      require TF and DnaK for folding. GroEL/GroES thus influences the folding of
      proteins previously identified as DnaK/TF substrates.

PMID- 14960334
TI  - Expression of Disrupted-In-Schizophrenia-1, a schizophrenia-associated gene, is
      prominent in the mouse hippocampus throughout brain development.
AB  - DISC1 (Disrupted-In-Schizophrenia 1) has been associated with schizophrenia in
      multiple genetic studies. Studies from our laboratory have shown that Disc1, the
      mouse ortholog of DISC1, is highly expressed in the dentate gyrus of the
      hippocampus in the adult mouse brain. Because developmental dysfunction of the
      hippocampus is thought to play a major role in schizophrenia pathogenesis, and
      the dentate gyrus is a major locus for adult neurogenesis in the mouse, we
      investigated Disc1 expression during mouse brain development. Strikingly, Disc1
      is strongly expressed in the hippocampus during all stages of hippocampal
      development, from embryonic day 14 through adulthood. Disc1 mRNA was detected in
      the dentate gyrus at all stages in which this structure was identifiable, as well
      as in the cornu ammonis (CA) fields of the hippocampus, the subiculum and
      adjacent entorhinal cortex, and the developing cerebral neocortex, hypothalamus,
      and olfactory bulbs, all of which also express Disc1 in the adult mouse brain. In
      addition, Disc1 mRNA was seen in regions of the developing mouse brain which do
      not express Disc1 during adulthood, regions including the bed nucleus of the
      stria terminalis, reticular thalamic nucleus and reuniens thalamic nucleus. These
      results demonstrate that Disc1 marks the hippocampus from its earliest stages,
      and suggest that developmental Disc1 dysfunction may lead to defects in
      hippocampal function that are associated with schizophrenia.

PMID- 14960335
TI  - Activation of mu opioid receptors in the medial preoptic area following
      copulation in male rats.
AB  - The current study tested the hypothesis that sexual behavior is a biological
      stimulus for release of endogenous opioid peptides. In particular, activation of
      mu opioid receptors (MOR) in the medial preoptic area (MPOA), a key area for
      regulation of male sexual behavior, was studied in male rats. MOR endocytosis or
      internalization was used as a marker for ligand-induced receptor activation,
      utilizing confocal, electron, and bright microscopic analysis. Indeed, mating
      including one ejaculation induced receptor activation in the MPOA, demonstrated
      by increased immunoreactivity for MOR, increased numbers of endosome-like
      particles immunoreactive for MOR inside the cytoplasm of neurons, and increased
      percentage of neurons with three or more endosome-like particles inside the
      cytosol. Moreover, it was demonstrated that MOR activation occurred within 30 min
      following mating and was still evident after 6 h. Mating-induced internalization
      was prevented by treatment with the opioid receptor antagonist naloxone before
      mating, suggesting that mating-induced receptor activation is a result of action
      of endogenous MOR ligands. i.c.v. injections of MOR ligand [D-Ala(2), N-Me
      Phe(4), Gly(5)-ol]-enkephalin resulted in internalization of the MOR in a similar
      manner observed following mating. Finally, mating induced Fos expression in MOR
      containing neurons in the MPOA. However, naloxone pretreatment did not prevent
      Fos activation of MOR neurons, suggesting that Fos induction was not the result
      of MOR activation. In summary, these results provide further evidence that
      endogenous opioid peptides are released in the MPOA during male sexual behavior.

PMID- 14960336
TI  - Dorsal striatum and stimulus-response learning: lesions of the dorsolateral, but
      not dorsomedial, striatum impair acquisition of a stimulus-response-based
      instrumental discrimination task, while sparing conditioned place preference
      learning.
AB  - While some evidence suggests that the dorsal striatum is important for stimulus
      response learning, disagreement exists about the relative contribution of the
      dorsolateral and dorsomedial striatum to this form of learning. In the present
      experiment, the effects of lesions of the dorsolateral and dorsomedial striatum
      were investigated on two tasks that differentially require the development of
      stimulus-response learning. The first task utilized an operant conditional
      discrimination task, which is likely to rely heavily upon stimulus-response
      learning. The second task looked conditioned place preference learning, a task
      that is unlikely to require the development of stimulus-response associations.
      Animals with lesions of the dorsolateral striatum were impaired on the operant
      conditional discrimination task, but retained the ability to learn the
      conditioned place preference task. In contrast, animals with lesions of the
      dorsomedial striatum were not found to be impaired on either task used in the
      present experiment. These results suggest that the dorsolateral striatum is
      necessary for the successful acquisition of tasks that place a demand upon
      stimulus-response learning, while the dorsomedial striatum is not involved in
      this type of learning.

PMID- 14960337
TI  - A 68930 and dihydrexidine inhibit locomotor activity and d-amphetamine-induced
      hyperactivity in rats: a role of inhibitory dopamine D(1/5) receptors in the
      prefrontal cortex?
AB  - The behavioral and biochemical effects of the full dopamine D(1/5) receptor
      agonists, dihydrexidine and (1R,3S)-1-aminomethyl-5,6-dihydroxy-3
      phenylisochroman HCl (A 68930), were examined in rats. Both A 68930 (0-4.6 mg kg(
      1), s.c.) and dihydrexidine (0-8.0 mg kg(-1), s.c.) caused a dose-dependent
      suppression of locomotor activity, as assessed in an open-field. This locomotor
      suppression was dose-dependently antagonized by the selective dopamine D(1/5)
      receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro
      1H-3-benzazepine HCl (SCH 23390; 0-5.0 microg kg(-1), s.c.), but not by the
      selective dopamine D(2/3) receptor antagonist raclopride (0-25.0 microg kg(-1),
      s.c.). Furthermore, A 68930 and dihydrexidine did not cause any locomotor
      activity in habituated rats that displayed a very low base-line activity. Neither
      did A 68930 nor dihydrexidine produce any excessive stereotypies that could
      possibly interfere with and mask ambulatory activity. In fact, both A 68930 and
      dihydrexidine potently blocked hyperactivity produced by d-amphetamine (0-4.0 mg
      kg(-1), s.c.). Such findings traditionally would be interpreted as a sign of
      potential antipsychotic properties of A 68930 and dihydrexidine. Examination of
      neuronal activation, as indexed by the immediate early gene c-fos, showed that A
      68930 and dihydrexidine caused a highly significant expression of c-fos in the
      medial prefrontal cortex. This c-fos expression was sensitive to treatment with
      SCH 23390, but not with raclopride. The effects of A 68930 and dihydrexidine on c
      fos expression in caudate putamen or nucleus accumbens were less marked, or
      undetectable. The results indicate that stimulation of dopamine D(1/5) receptors,
      possibly in the medial prefrontal cortex, is associated with inhibitory actions
      on locomotor activity and d-amphetamine-induced hyperactivity. Assuming an
      important role of prefrontal dopamine D(1/5) receptors in schizophrenia, such
      inhibitory actions of dopamine D(1/5) receptor stimulation on psychomotor
      activation may have interesting clinical implications in the treatment of
      schizophrenia.

PMID- 14960338
TI  - Novel spatial arrangements of familiar visual stimuli promote activity in the rat
      hippocampal formation but not the parahippocampal cortices: a c-fos expression
      study.
AB  - The novelty of a cue may arise from the presence of an element that has not
      previously been experienced or from familiar elements that have been rearranged.
      The present study mapped the anatomical basis of responding to this second form
      of novelty. For this, rats were trained on a working memory spatial task in a
      radial-arm maze in a cue-controlled environment. On the final test day the
      positions of the familiar, extra-maze cues were rearranged for half of the rats
      (group Novel). The spatial configuration of the cues now matched that of the
      control rats (group Familiar). Neuronal activation, as measured by the immediate
      early gene, c-fos, was then compared between the two groups. Rearrangement of
      visual stimuli led to significant increases in Fos-positive cells in various
      hippocampal subfields (rostral CA1, rostral CA3 and rostral dentate gyrus) as
      well as the parietal cortex and the postsubiculum. In contrast, no changes were
      observed in other sites including the perirhinal cortex, postrhinal cortex,
      lateral and medial entorhinal cortices, retrosplenial cortices, or anterior
      thalamic nuclei. These results highlight the selective involvement of the
      hippocampus for processing novel rearrangements of visual stimuli and suggest
      that this involvement is intrinsic as it is independent of the parahippocampal
      cortices. This pattern of Fos changes is the mirror image of that repeatedly
      found for novel individual stimuli (perirhinal increase, no hippocampal change),
      demonstrating that these two forms of novelty have qualitatively different neural
      attributes.

PMID- 14960339
TI  - Gene expression in autonomic areas of the medulla and the central nucleus of the
      amygdala in rats during and after space flight.
AB  - During space flight astronauts show vestibular-related changes in balance, eye
      movements, and spontaneous and reflex control of cardiovascular, respiratory and
      gastrointestinal function, sometimes associated with space motion sickness. These
      symptoms undergo compensation over time. Here we used changes in the expression
      of two immediate-early gene (IEG) products to identify cellular and molecular
      changes occurring in autonomic brainstem regions of adult male albino rats killed
      at different times during the Neurolab Space Mission (STS-90). Both direct
      effects of gravitational changes, as well as indirect effects of gravitational
      changes on responses to light exposure were examined. Regions under the direct
      control of vestibular afferents such as the area postrema and the caudal part of
      the nucleus of the tractus solitarius (NTSC) were both directly and indirectly
      affected by gravity changes. These areas showed no changes in the expression of
      IEG products during exposure to microgravity with respect to ground controls, but
      did show a significant increase 24 h after return to 1 G (gravity). Exposure to
      microgravity significantly inhibited gene responses to light exposure seen after
      return to 1 G. A similar direct and indirect response pattern was also shown by
      the central nucleus of the amygdala, a basal forebrain structure anatomically and
      functionally related to the NTS. The rostral part of the NTS (NTSR) receives
      different afferent projections than the NTSC. This region did not show any direct
      gravity-related changes in IEG expression, but showed an indirect effect of
      gravity on IEG responses to light. A similar pattern was also obtained in the
      intermediate reticular nucleus and the parvocellular reticular nucleus. Two other
      medullary reticular structures, the dorsal and the ventral medullary reticular
      nuclei showed a less well defined pattern of responses that differed from those
      seen in the NTSC and NTSR. The short- and long-lasting molecular changes in
      medullary and basal forebrain gene expression described here are thought to play
      an important role in the integration of autonomic and vestibular signals that
      ultimately regulate neural adaptations to space flight.

PMID- 14960340
TI  - Effects of voluntary exercise on synaptic plasticity and gene expression in the
      dentate gyrus of adult male Sprague-Dawley rats in vivo.
AB  - We have previously shown that voluntary exercise produces enhanced neurogenesis
      and long-term potentiation (LTP) in the dentate gyrus (DG) of mice in vitro. In
      the present experiments we show that rats given access to a running wheel
      (Runners) exhibit significantly more short-term potentiation and LTP with theta
      patterned conditioning stimulation in vivo than do age-matched litter mates
      (Controls). This increase in LTP appears to reflect an alteration in the
      induction threshold for synaptic plasticity that accompanies voluntary exercise.
      Weak theta-patterned stimulation, which did not produce LTP in control subjects,
      produced a robust and long-lasting LTP in Runners. LTP induction in both groups
      was dependent upon the activation of N-methyl-D-aspartate (NMDA) receptors, and
      could be blocked by the competitive antagonist [+/-]-3-[2-carboxypiperazin-4-yl]
      propanephosphonic acid. Consistent with these findings, we found that mRNA levels
      for NR2B subtype of NMDA receptor were increased specifically in the DG of
      Runners. In addition to changes in NR2B mRNA levels, quantitative polymerase
      chain reaction analysis revealed that brain-derived neurotrophic factor (BDNF)
      and glutamate receptor 5 mRNA levels were also significantly elevated in the DG
      of Runners, but not in other areas of the hippocampus. Thus, alterations in the
      expression of BDNF, and specific glutamate receptor subtypes, may underlie the
      ability of exercise to enhance neurogenesis and reduce the threshold for LTP in
      the DG.

PMID- 14960341
TI  - Neuropeptide FF, but not prolactin-releasing peptide, mRNA is differentially
      regulated in the hypothalamic and medullary neurons after salt loading.
AB  - Hypothalamic paraventricular and supraoptic nuclei are involved in the body fluid
      homeostasis. Especially vasopressin peptide and mRNA levels are regulated by hypo
      and hyperosmolar stimuli. Other neuropeptides such as dynorphin, galanin and
      neuropeptide FF are coregulated with vasopressin. In this study neuropeptide FF
      and another RF-amide peptide, the prolactin-releasing peptide mRNA levels were
      studied by quantitative in situ hybridization after chronic salt loading, a
      laboratory model of chronic dehydration. The neuropeptide FF mRNA expressing
      cells virtually disappeared from the hypothalamic supraoptic and paraventricular
      nuclei after salt loading, suggesting that hyperosmolar stress downregulated the
      NPFF gene transcription. The neuropeptide FF mRNA signal levels were returned to
      control levels after the rehydration period of 7 days. No changes were observed
      in those medullary nuclei that express neuropeptide FF mRNA. No significant
      changes were observed in the hypothalamic or medullary prolactin-releasing
      peptide mRNA levels. Neuropeptide FF mRNA is drastically downregulated in the
      hypothalamic magnocellular neurons after salt loading. Other neuropeptides
      studied in this model are concomitantly coregulated with vasopressin: i.e. their
      peptide levels are downregulated and mRNA levels are upregulated which is in
      contrast to neuropeptide FF regulation. It can thus be concluded that
      neuropeptide FF is not regulated through the vasopressin regulatory system but
      via an independent pathway. The detailed mechanisms underlying the downregulation
      of neuropeptide FF mRNA in neurons remain to be clarified.

PMID- 14960342
TI  - Transcription factor tonicity-responsive enhancer-binding protein (TonEBP) which
      transactivates osmoprotective genes is expressed and upregulated following acute
      systemic hypertonicity in neurons in brain.
AB  - Tonicity-responsive enhancer-binding protein (TonEBP) was initially identified as
      a transcription factor involved in adaptation of renal cells to hypertonicity by
      activation of osmoprotective genes encoding proteins for accumulation of
      compatible osmolytes. Since brain osmoadaptation is observed in relationship to
      neurological disorders resulting from pathological osmotic disbalances of blood
      plasma we have investigated through immunocytochemistry TonEBP expression in
      cerebral cortex and hippocampus of normal rat and rats submitted to an acute
      systemic hypertonicity or to a prolonged systemic hypotonicity. TonEBP-expressing
      cells were identified using double immunofluorescence and appropriate cell type
      markers. Their relative proportion was determined by quantitative image analysis.
      In normal rats TonEBP expressed primarily in neurons where it was strictly
      located in the cell nucleus but heterogeneously distributed into a nucleoplasmic
      pool and a granular pool. In animals made acutely hypertonic TonEBP labeling
      increased dramatically exclusively in the nuclei of neurons and reached a maximum
      within 1 h. In hypertonic animals TonEBP labeling covered the whole cell nucleus
      of virtually all neurons, appeared finely punctuated but was no more granular.
      Optical density of the labeling as determined by image analysis correlated
      linearly with the increased plasma osmolality. In animals made hypotonic for
      several days no conspicuous decrease of TonEBP labeling was observed. In normal
      animals a very minor proportion of non-neuronal cells showed a faint TonEBP
      nuclear labeling. This proportion increased slightly in hypertonic animals.
      Nevertheless these non-neuronal TonEBP-positive nuclei which belonged to
      oligodendrocytes and to a small subpopulation of astrocytes remained always very
      weakly labeled when compared with neuron nuclei. Brain capillary endothelial
      cells as well as microglial cells showed no TonEBP-labeling even in hypertonic
      animals. Our data demonstrate that in brain TonEBP is significantly expressed and
      tonicity-overexpressed in neurons and accordingly suggest that neurons only among
      brain cells accumulate compatible osmolytes through TonEBP-mediated activation of
      osmoprotective genes to adapt to acute systemic hypertonicity.

PMID- 14960343
TI  - Temporal dissociation of the feedback effects of dendritically co-released
      peptides on rhythmogenesis in vasopressin cells.
AB  - Vasopressin neurones fire action potentials in a rhythmic 'phasic' pattern,
      characterised by alternating periods of activity and silence. Vasopressin and
      dynorphin are co-packaged in neurosecretory vesicles that are exocytosed from
      vasopressin cell dendrites and terminals and both have been implicated in the
      generation of phasic activity patterning through autoregulatory mechanisms. Here,
      identified supraoptic nucleus vasopressin cells exhibiting spontaneous phasic
      activity were recorded from urethane-anaesthetised rats administered the V1
      vasopressin receptor antagonist, OPC 21268, or the kappa-opioid receptor
      antagonist, nor-binaltorphimine. OPC 21268 elevated firing rate throughout each
      burst whereas nor-binaltorphimine excitation emerged over the course of each
      burst, indicating a progressive activation of kappa-opioid receptor mechanisms
      during bursts. To determine whether changes in post-spike excitability could
      account for these effects, we plotted the probability of action potential firing
      with time after the preceding action potential (hazard function) and found that,
      similarly to firing rate, this too was elevated by OPC 21268 throughout each
      burst whilst the excitatory effects of nor-binaltorphimine progressively
      increased over the course of each burst. Thus, the temporal organisation of the
      feedback effects of these co-released peptides is different, with vasopressin
      effectively causing an immediate reduction in overall excitability whilst
      dynorphin causes a progressive decrease in post-spike excitability over the
      course of each burst.

PMID- 14960344
TI  - A functional magnetic resonance imaging study of local/global processing with
      stimulus presentation in the peripheral visual hemifields.
AB  - When stimuli are presented in the left or right visual fields, hemispheric
      specialization for global and local processing in occipital areas is attenuated.
      Using functional magnetic resonance imaging, we investigated how this attenuation
      is compensated for when information must cross the corpus callosum to reach the
      areas specialized for global and local processing. We presented hierarchically
      nested letters (e.g. a large E made of smaller E's) to the right or the left
      visual hemifield while subjects fixated centrally. In half the trials, subjects
      indicated whether the global aspect and in the other half whether the local
      aspect of the stimulus matched a pre-specified target letter. Visual hemifield
      presentations showed the expected contralateral activations of occipital cortex.
      The main effects of locally or globally directed attention did not show any
      differential occipital activations, but the right anterior cingulate cortex was
      activated differentially during local processing. Region-of-interest-based
      analyses showed increased neural activity in left posterior occipital cortex
      during local processing when stimuli were presented in the left hemifield. During
      global processing with stimulus presentation to the right hemifield, the right
      posterior occipital cortex was activated. Activation of right anterior cingulate
      cortex during local processing is likely to reflect the suppression of global
      processing precedence in order to select correctly the local stimulus level. The
      activations in left (local) and right (global) occipital areas are likely to
      reflect the top-down augmentation of stimulus information that has been degraded
      by callosal crossing in order to access the hemisphere specialized for local or
      global processing.

PMID- 14960345
TI  - Binocular fusion/suppression to spatial frequency differences at the border of
      areas 17/18 of the cat.
AB  - As shown by various human psychophysical studies, interocular spatial frequency
      disparities can yield a variety of percepts. In order to examine how binocular
      fusion is affected by spatial frequency differences, we have recorded cells in
      the border region of areas 17/18 of anesthetized cats. The optic axes of the eyes
      were deviated onto cathode-ray screens, and the optimal spatial frequency of each
      eye was assessed by monocular stimulations using drifting sinusoidal gratings.
      The optimal relative phase using identical spatial frequencies in both eyes was
      first determined. Spatial frequency differences were then introduced by keeping
      the optimal spatial frequency constant in one eye and varying the spatial
      frequency in the other. Results indicate that cells (39%) responded with an
      increased firing rate (facilitation) to similar spatial frequencies in each eye
      and with a gradual attenuation (occlusion or suppression) when spatial frequency
      differences were increased. However, binocular facilitation did not always occur
      to the presentation of identical stimuli. For 16% of the cells, maximal responses
      were observed when lower spatial frequencies than the optimal one were presented
      in one eye while higher spatial frequencies produced suppression. The opposite
      pattern was observed only for two cells. These findings are discussed in terms of
      binocular fusion and suppression.

PMID- 14960346
TI  - Glial cell line-derived neurotrophic factor is essential for neuronal survival in
      the locus coeruleus-hippocampal noradrenergic pathway.
AB  - It has been shown that the noradrenergic (NE) locus coeruleus (LC)-hippocampal
      pathway plays an important role in learning and memory processing, and that the
      development of this transmitter pathway is influenced by neurotrophic factors.
      Although some of these factors have been discovered, the regulatory mechanisms
      for this developmental event have not been fully elucidated. Glial cell line
      derived neurotrophic factor (GDNF) is a potent neurotrophic factor influencing LC
      NE neurons. We have utilized a GDNF knockout animal model to explore its function
      on the LC-NE transmitter system during development, particularly with respect to
      target innervation. By transplanting various combinations of brainstem (including
      LC) and hippocampal tissues from wildtype or GDNF knockout fetuses into the
      brains of adult wildtype mice, we demonstrate that normal postnatal development
      of brainstem LC-NE neurons is disrupted as a result of the GDNF null mutation.
      Tyrosine hydroxylase immunohistochemistry revealed that brainstem grafts had
      markedly reduced number and size of LC neurons in transplants from knockout
      fetuses. NE fiber innervation into the hippocampal co-transplant from an adjacent
      brainstem graft was also influenced by the presence of GDNF, with a significantly
      more robust innervation observed in transplants from wildtype fetuses. The most
      successful LC/hippocampal co-grafts were generated from fetuses expressing the
      wildtype GDNF background, whereas the most severely affected transplants were
      derived from double transplants from null-mutated fetuses. Our data suggest that
      development of the NE LC-hippocampal pathway is dependent on the presence of
      GDNF, most likely through a target-derived neurotrophic function.

PMID- 14960347
TI  - Neurokinin 1 receptor expression and substance P physiological actions are
      developmentally regulated in the rabbit retina.
AB  - We investigated the expression of the substance P (SP) receptor (the neurokinin 1
      receptor, NK1 receptor) and SP functional effects in developing rabbit retinas.
      NK1 receptors in adult retinas were in a population of cone bipolar cells and in
      dopaminergic amacrine cells, as previously described. In contrast, at birth and
      at postnatal day (PND) 6, NK1 receptors were exclusively expressed by cholinergic
      amacrine and displaced amacrine cells. NK1 receptor expression in cholinergic
      cells was still observed at PND10 (eye opening), while at PND21 it was confined
      to cholinergic cells of the inner nuclear layer. Starting at PND10, NK1 receptors
      were also in bipolar cells and in dopaminergic amacrine cells. A fully mature NK1
      receptor expression pattern was observed at PND35. Dopamine release was assessed
      in isolated retinas in the presence of SP, the NK1 receptor agonist GR73632 or
      the NK1 receptor antagonist GR82334. At PND35, extracellular dopamine was
      significantly increased by 10 microM SP or 0.01-100 microM GR73632, and it was
      decreased by 0.01-10 microM GR82334. No effects were detected in developing
      retinas up to PND21. Ca2+ imaging experiments were performed in single
      cholinergic cells identified by their "starburst" morphology in perinatal
      retinas. Intracellular Ca2+ levels were significantly increased by 1 microM SP or
      GR73632. This effect was reversibly inhibited by 1 microM GR82334. These data
      demonstrate that both NK1 receptor expression and SP physiological actions are
      developmentally regulated in the retina. SP neurotransmission in the immature
      retina may subserve developmental events, and SP is likely to represent an
      important developmental factor for the maturation of retinal neurons and
      circuitries.

PMID- 14960348
TI  - GABAA receptor maturation in relation to eye opening in the rat visual cortex.
AB  - Changes in subunit composition of N-methyl-D-aspartate (NMDA) receptors have been
      reported to be affected by visual experience and may therefore form a major
      aspect of neuronal plasticity in the CNS during development. In contrast,
      putative alterations in the expression and functioning of the inhibitory GABAA
      receptor around eye opening have not been well defined yet. Here we describe the
      timing of changes in GABAA receptor subunit expression and the related synaptic
      functioning in the neonatal rat visual cortex and the influence of visual
      experience on this process. Quantitative analysis of all GABAA receptor subunit
      transcripts revealed a marked alpha3 to alpha1 subunit switch, in addition to a
      change in alpha4 and alpha5 expression. The changes were correlated with an
      acceleration of the decay of spontaneous inhibitory postsynaptic currents
      (sIPSCs). Both changes in receptor expression and synaptic functioning were
      initiated well before eye opening. Moreover, dark rearing could not prevent the
      robust upregulation of alpha1 or the change in sIPSC kinetics, indicating that
      this is not dependent of sensory (visual) input. Upon eye opening a positive
      correlation was observed between a faster decay of the sIPSCs and an increase in
      sIPSC frequency, which was absent in dark-reared animals. Thus, lack of extrinsic
      input to the cortex does not affect overall developmental regulation of synaptic
      functioning of GABAA receptors. However, we cannot exclude the possibility that
      visual experience is involved in proper shaping of the inhibitory network of the
      primary visual cortex.

PMID- 14960349
TI  - Neurogenesis in olfactory bulb identified by retroviral labeling in normal and 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated adult mice.
AB  - Neurogenesis occurs during development and in the normal adult brain. Recent
      studies identified areas exhibiting postlesional selective neurogenesis and
      neuronal repair. In the olfactory bulb (OB), one of the most studied regions of
      the brain for neurogenesis, seizures and strong odor exposure are known to
      enhance neurogenesis. Here, we report enhanced neurogenesis in OB after
      dopaminergic neuronal loss induced by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), a selective toxin for dopaminergic neurons. The
      neurogenesis has been previously confirmed mainly by the uptake of 5
      bromodeoxyuridine (BrdU), a marker of proliferating cells, but methodological
      problems related to BrdU labeling might result in inaccurate findings with
      respect to specificity, toxicity and incorporation into normal/lesioned brain.
      For a better identification of neurogenesis, we used a retroviral vector. First,
      we investigated the population dynamics of newly formed neurons in different
      regions of OB including the glomerular layer, the most superficial layer of OB.
      Quantification of neurogenesis in OB revealed by our retroviral vector was
      substantially similar to that by BrdU-based method. One week after MPTP
      application and dopaminergic neuronal loss in OB, neurogenesis of dopaminergic
      neurons in OB increased by three-fold, but no such process was noted in non
      dopaminergic neurons. Our results indicate selective dopaminergic neurogenesis in
      OB in response to neuronal damage/loss.

PMID- 14960350
TI  - Latent inhibition is spared by N-methyl-D-aspartate (NMDA)-induced ventral
      hippocampal lesions, but is attenuated following local activation of the ventral
      hippocampus by intracerebral NMDA infusion.
AB  - Repeated non-reinforced exposures of a neutral stimulus retard the development of
      a conditioned response to that stimulus when it is subsequently paired with a
      significant event. This stimulus pre-exposure effect is known as latent
      inhibition (LI). Early lesion studies have initially suggested an important role
      for the hippocampus in the normal development and expression of LI. This view has
      since been modified with the emergence of data derived from selective cell body
      lesions of the hippocampus and of the entorhinal cortex, with an abolition of LI
      only seen after lesions of the latter. This suggests that the significance of the
      hippocampus might have been overestimated in the past, possibly due to
      interruption of fibres en passage. However, intact behavioural expression of LI
      following hippocampal damage does not preclude the suggestion that the
      hippocampus participates in the control and regulation of LI expression in intact
      animals. The present study demonstrated that whilst cell body lesions of the
      ventral hippocampus spared LI (as expected), chemical activation of the ventral
      hippocampus by local N-methyl-D-aspartate infusion disrupted LI. These results
      parallel our earlier observations on prepulse inhibition (PPI) with similar
      manipulations [Neuroreport 10 (1999) 2533]. Thus, although the ventral
      hippocampus is itself not responsible for the behavioural manifestation of LI and
      PPI, it exerts at least a modulatory control over the form and/or magnitude of
      their expression. Our results should prompt a re-evaluation of the relative roles
      of the hippocampus and retrohippocampus in the development and expression of LI.

PMID- 14960351
TI  - Inhibition of type A GABA receptors by L-type calcium channel blockers.
AB  - Modulation of type A GABA receptors (GABAA) by L-type Ca++ channel blockers was
      investigated. The dihydropyridines nifedipine and nitrendipine, and the
      phenylalkylamine verapamil inhibited recombinant rat alpha1beta2gamma2 receptors
      recorded from human embryonic kidney (HEK) 293 cells; nifedipine at low
      concentrations also elicited modest stimulatory effects on GABA-gated current.
      The IC50 for GABA current inhibition was lowest for nitrendipine (17.3 +/- 1.3
      microM), so subsequent studies were focused on further exploring its mechanism
      and possible site of action. When co-applied with GABA, nitrendipine had minimal
      effects on initial current amplitude, but significantly enhanced current decay
      rate. Nitrendipine-mediated inhibition was subunit-selective, as its IC50 was 10
      fold lower in alpha1beta2 receptors. Nitrendipine's effect in recombinant human
      alpha1beta2gamma2 receptors was similar (IC50=23.0 +/- 1.3 microM) to that
      observed in rat receptors of the same configuration, indicating the site of
      action is conserved in the two species. The inhibitory effects were dependent on
      channel gating, were independent of transmembrane voltage, and were also observed
      in GABAA receptors recorded from hypothalamic brain slices. The pharmacologic
      mechanism of inhibition by nitrendipine was non-competitive, indicating it does
      not act at the GABA binding site. Nitrendipine block was retained in the presence
      of the benzodiazepine antagonist flumazenil, indicating it does not interact at
      the benzodiazepine site. The actions of nitrendipine were not affected by a
      mutation (beta2T246F) that confers resistance to the channel blocker picrotoxin,
      and they were not altered in the presence of the picrotoxin site antagonist alpha
      isopropyl-alpha-methyl-gamma-butyrolactone, demonstrating nitrendipine does not
      act at the picrotoxin site of the GABAA receptor. Possible interaction of
      nitrendipine with the Zn++ site was also eliminated, as mutation of beta2 H267 to
      A, which confers resistance to Zn++, had no effect on nitrendipine-mediated
      inhibition. Our data suggest some of the central effects of dihydropyridines may
      be due to actions at GABAA receptors. Moreover, the effects may be mediated
      through interaction with a novel modulatory site on the GABAA receptor.

PMID- 14960352
TI  - Evidence for a role of basal ganglia in the regulation of rapid eye movement
      sleep by electrical and chemical stimulation for the pedunculopontine tegmental
      nucleus and the substantia nigra pars reticulata in decerebrate cats.
AB  - The present study was to determine how afferents from the substantia nigra pars
      reticulata (SNr) of the basal ganglia to the pedunculopontine tegmental nucleus
      (PPN) in the brainstem could contribute to the control of behavioral states. We
      used anesthetized and acutely decerebrated cats (n=22). Repetitive electrical
      stimulation (10-100 Hz, 20-50 microA, for 4-20 s) to the ventrolateral part of
      the PPN produced rapid eye movement (REM) associated with a suppression of
      postural muscle tone (REM with atonia). Although repetitive electrical stimuli
      (10-200 Hz, 10-60 microA, for 5-20 s) delivered to the dorsolateral part of the
      SNr did not evoke eye movements or muscular tonus in baseline conditions, it
      altered the PPN-induced REM with atonia. The following three types of effects
      were induced: (1) attenuation of the REM with atonia; (2) attenuation of muscular
      atonia without changes in REM (REM without atonia); and (3) attenuation of only
      REM. The optimal stimulus sites for these effects were intermingled within the
      lateral part of the SNr. The PPN-induced REM with atonia was abolished by an
      injection into the PPN of muscimol (1-15 mM, 0.1-0.25 microl), a GABAA receptor
      agonist, but not altered by an injection of baclofen (1-10 mM, 0.1-0.25 microl),
      a GABAB receptor agonist. Moreover, an injection of bicuculline (1-15 mM, 0.1
      0.25 microl), a GABAA receptor antagonist, into the PPN, resulted in REM with
      atonia. On the other hand, an injection of muscimol into the dorsolateral part of
      the SNr (1-15 mM, 0.1-0.25 microl) induced REM with atonia, which was in turn
      eliminated by a further injection of muscimol into the PPN (5-10 mM, 0.2-0.25
      microl). These results suggest that a GABAergic projection from the SNr to the
      PPN could be involved in the control of REM with atonia, signs which indicate REM
      sleep. An excessive GABAergic output from the basal ganglia to the PPN in
      parkinsonian patients may induce sleep disturbances, including a reduction of REM
      sleep periods and REM sleep behavioral disorders (REM without atonia).

PMID- 14960353
TI  - Close anatomical associations between beta-endorphin and luteinizing hormone
      releasing hormone neuronal systems in the human diencephalon.
AB  - Endogenous opiates, such as beta-endorphin, inhibit the release of luteinizing
      hormone (LH) release in the pituitary gland of several species including rat,
      pig, sheep, and human. Although it is generally believed that beta-endorphin
      influences gonadal functions via the regulation of hypothalamic LH-releasing
      hormone (LHRH) release, the morphological substrate underlying this regulation in
      humans remains elusive. In the present series of experiments the beta-endorphin
      immunoreactive (IR) and LHRH-IR neural elements, utilizing single label
      immunohistochemistry, were mapped. Following the superimposition of the maps of
      these systems, the overlapping sites were identified and examined in order to
      verify the putative juxtapositions between the beta-endorphin-IR and LHRH-IR
      structures. LHRH-IR elements were detected mainly in the medial basal
      hypothalamus, in the medial preoptic area and along the diagonal band of Broca.
      Beta-endorphin-IR perikarya were observed in the infundibular region/median
      eminence, whereas beta-endorphin-IR axon varicosities were detected
      periventricularly in the preoptic and tuberal regions, in the medial basal
      hypothalamus and around the mamillary bodies. Careful examination of the
      immunoreactive elements in the overlapping areas revealed close contacts between
      beta-endorphin-IR and LHRH-IR structures, which have been verified in semithin
      plastic sections. These putative beta-endorphin-LHRH juxtapositions were most
      numerous in the medial preoptic area and in the infundibulum/median eminence of
      the human diencephalon. In conclusion, the present paper is the first study that
      revealed close juxtapositions between the beta-endorphin-IR and LHRH-IR neural
      elements in the human diencephalon. These beta-endorphin-LHRH contacts may be
      functional synapses, and they may be the morphological substrate of the beta
      endorphin control on gonadal functions in man.

PMID- 14960354
TI  - Synaptic responsiveness of neocortical neurons to callosal volleys during
      paroxysmal depolarizing shifts.
AB  - Based on intracellular recordings in vivo, we investigated the responsiveness of
      cat neocortical neurons to callosal volleys during different phases of
      spontaneously occurring or electrically induced electrographic seizures, compared
      with control periods of slow sleep-like oscillations. Overt seizures, with
      spiking, triggered by pulse-trains to the callosal pathway, started with a
      latency of approximately 20 s after cessation of stimulation, thus contrasting
      with paroxysmal activity elicited by ipsilateral cortical or thalamic stimulation
      that is initiated immediately after electrical stimulation. During the rather
      long preparatory period to callosally triggered seizures, cortical neurons
      displayed subthreshold depolarizing runs at 4-7 Hz, associated with increased
      amplitudes of excitatory postsynaptic potentials. The sequential analysis of
      neuronal responsiveness during different components of spike-wave complexes
      revealed progressively increased amplitudes of callosally evoked postsynaptic
      excitatory responses in regular-spiking and fast-rhythmic-bursting neurons, over
      a period of approximately 20 ms prior to the generation of paroxysmal
      depolarizing shifts. These data support the concept that seizures consisting of
      spike-wave complexes originate within the neocortex through a progressive
      synaptic buildup and that their synchronization is achieved, at least partially,
      by cortical commissural synaptic linkages.

PMID- 14960355
TI  - Endogenous opioids mediate basal hedonic tone independent of dopamine D-1 or D-2
      receptor activation.
AB  - Exogenously administered opiates are recognized as rewarding and the involvement
      of dopamine systems in mediating their apparent pleasurable effects is
      contentious. The aversive response to naloxone administration observed in animal
      studies suggests the presence of an endogenous opioid tone regulating hedonic
      state. We sought evidence for the requirement for dopamine systems in mediating
      this action of endogenous opioids by determining whether mice deficient in
      dopamine D-1 or D-2 receptors were able to display conditioned place aversion to
      naloxone. Mice received saline in the morning in one chamber and either saline or
      naloxone (10 mg/kg, s.c.) in the afternoon in another chamber, each day for 3
      days. On the test day they were given free access to the testing chambers in the
      afternoon. Similar to their wild-type littermates, D-1 and D-2 receptor knockout
      mice receiving naloxone in the afternoon spent significantly less time on the
      test day in the compartment in which they previously received naloxone, compared
      with animals receiving saline in the afternoon. The persistence of naloxone
      conditioned place aversion in D-1 and D-2 knockout mice suggests that endogenous
      opioid peptides maintain a basal level of positive affect that is not dependent
      on downstream activation of dopamine systems involving D-1 or D-2 receptors.

PMID- 14960356
TI  - Role of the amygdalo-hippocampal transition area in the fear expression:
      evaluation by behavior and immediate early gene expression.
AB  - Using pre- and post-training lesions of the amygdalo-hippocampal transition area
      (AHi), the role of the AHi in the fear conditioning of rats was examined.
      Pretraining lesions by N-methyl-d-aspartate led to the enhancement of freezing
      behavior in auditory fear conditioning and contextual conditioning. However, the
      freezing of post-training-lesioned rats did not differ from that of the sham
      lesioned rats. There were several regions of the brain observed in this study in
      which c-Fos and/or Egr-1 immunoreactive-positive cell expression changed in
      diverse manners after the test session. In the pretraining lesioned rats that
      were trained for auditory conditioning, the number of c-Fos and Egr-1 decreased
      in the infralimbic cortex (IL) and the number of Egr-1 increased in the
      basomedial amygdaloid nucleus (BM). In the pretraining AHi-lesioned rats that
      were trained for contextual conditioning, the number of c-Fos increased in the
      lateral periaqueductal gray (LPAG) and the number of Egr-1 increased in the BM.
      These results suggest that the AHi plays an important role in the acquisition of
      memory during conditioning alone, whereas it is improbable that the AHi had an
      effect on consolidation, retrieval, and expression in the case of either auditory
      or contextual fear conditioning. The findings also suggest that the freezing
      behavior was related to the changes in c-Fos and/or Egr-1 in the IL, BM, and
      LPAG. As in the case of the BM, the number of Egr-1 immunoreactive-positive cells
      was increased in both experiments, and it was possible that the activation of
      neurons with high basal levels of expression might be associated with memory
      retrieval or expression as a freezing behavior observed in the test session.

PMID- 14960357
TI  - Transcriptional control of B cell development and function.
AB  - The generation, development, maturation and selection of mammalian B lymphocytes
      is a complex process that is initiated in the embryo and proceeds throughout life
      to provide the organism an essential part of the immune system it requires to
      cope with pathogens. Transcriptional regulation of this highly complex series of
      events is a major control mechanism, although control is also exerted on all
      other layers, including splicing, translation and protein stability. This review
      summarizes our current understanding of transcriptional control of the well
      studied murine B cell development, which bears strong similarity to its human
      counterpart. Animal and cell models with loss of function (gene "knock outs") or
      gain of function (often transgenes) have significantly contributed to our
      knowledge about the role of specific transcription factors during B
      lymphopoiesis. In particular, a large number of different transcriptional
      regulators have been linked to distinct stages of the life of B lymphocytes such
      as: differentiation in the bone marrow, migration to the peripheral organs and
      antigen-induced activation.

PMID- 14960358
TI  - NKX2.1 regulates transcription of the gene for human bone morphogenetic protein-4
      in lung epithelial cells.
AB  - Bone morphogenetic protein 4, BMP4, plays an important role in the development of
      various organs including the lungs. Little is known regarding the regulation of
      Bmp4 gene expression in any organ. In the lung, indirect evidence indicates that
      NKX2.1, a homeodomain transcriptional factor with a demonstrated role in lung
      morphogenesis, may be a potential upstream regulator of Bmp4 gene expression. In
      particular, Bmp4 mRNA is reduced or absent in Nkx2.1(-/-) lungs. The human Bmp4
      gene has been reported to include two regions of promoter activity in an
      embryonal carcinoma cell line, Tera2EC. The hBmp4.1 promoter is located upstream
      of exon I, whereas the second promoter, hBmp4.2, is localized within intron 1 and
      upstream of exon II. In the current study, we used a co-transfection assay in
      lung epithelial cells to examine the response of the two hBmp4 promoters to
      transcriptional stimulation by NKX2.1. Two DNA sequences were identified on the
      hBmp4.1 promoter that bind NKX2.1 and serve as functional cis-active NKX2.1
      responsive elements. Similarly, NKX2.1 stimulated transcription from the hBmp4.2
      promoter through two consensus binding sites localized within 412 nucleotides
      from the site of transcriptional initiation. Thus, both hBmp4 promoters include
      specific cis-active elements that bind to and mediate transcriptional regulation
      by NKX2.1. These findings bear functional implications regarding the regulation
      of a key signaling molecule by a homeodomain transcriptional regulator of lung
      epithelial morphogenesis.

PMID- 14960359
TI  - Mis-expression of the CLV3/ESR-like gene CLE19 in Arabidopsis leads to a
      consumption of root meristem.
AB  - Mild heat shock treatment (32 degrees C) of isolated Brassica napus microspores
      triggers a developmental switch from pollen maturation to embryo formation. This
      in vitro system was used to identify genes expressed in globular to heart-shape
      transition embryos. One of the genes isolated encodes a putative extra-cellular
      protein that exhibits high sequence similarity with the in silico identified
      CLV3/ESR-related 19 polypeptide from Arabidopsis (AtCLE19) and was therefore
      named BnCLE19. BnCLE19 is expressed in the primordia of cotyledons, sepals and
      cauline leaves, and in some pericycle cells in the root maturation zone. Mis
      expression of BnCLE19 or AtCLE19 in Arabidopsis under the control of the CaMV 35S
      promoter resulted in a dramatic consumption of the root meristem, the formations
      of pin-shaped pistils and vascular islands. These results imply a role of CLE19
      in promoting cell differentiation or inhibiting cell division.

PMID- 14960360
TI  - Gene expression profiles of livers from thermally injured rats.
AB  - The liver plays an important role in a severe thermal injury by modulating immune
      function, inflammatory processes and the acute phase response, which are an
      orchestrated attempt to restore homeostasis. Using high-density oligonucleotide
      arrays, we examined the gene expression profile in the livers of rats between 2
      and 240 h after a 40% total body surface area (TBSA) burn. Alterations in gene
      expression unique to a thermal injury were identified. Approximately 39 genes out
      of 8700 genes on each array across all the time points showed a significant
      change in expression patterns. Real time reverse transcription-polymerase chain
      reaction (RT-PCR) and Western blot analyses verified significant changes in early
      growth response-1 (Egr-1) messenger RNA (mRNA) and protein levels corresponding
      to the array data. Significant increases in serum levels of alpha-2-macroglobulin
      that correspond to changes in its mRNA levels were observed at 6 and 24 h after
      burn, p<0.05. The genomic pattern for liver in the hypermetabolic phase after the
      burn injury involves transcription factors, stress and inflammatory responses,
      cytoskeletal and extracellular matrix modifications, and regulation of cell
      proliferation and differentiation. During the initial phase of thermal injury
      gene expression profiles in the liver may provide some insight into how cellular
      protection mechanisms and systemic hypermetabolism are initiated and controlled.
      The genome wide changes observed may provide a rational therapeutic strategy to
      improve burn care.

PMID- 14960361
TI  - Homogeneity and long-term stability of tetracycline-regulated gene expression
      with low basal activity by using the rtTA2S-M2 transactivator and insulator
      flanked reporter vectors.
AB  - Inducible expression of tetracycline responsive element (TRE)-regulated genes in
      nearly all cells in a stable clone has generally been problematic, especially in
      long-term culture. Heterogeneity of tet-inducible expression is generally
      attributed to the instability of the original tet-transactivators tTA and rtTA.
      These transactivators have cryptic splice sites, prokaryotic codons and full VP16
      domains, all of which contribute to their instability. Moreover, they also
      require high concentrations of Doxycycline (Dox). The 5 amino acid substitutions
      in the rtTA variant rtTA2S-M2 confer exquisite sensitivity to Dox. Moreover,
      humanized codons, removal of cryptic splice sites and minimal VP16 domains in
      rtTA2S-M2 results in its being better tolerated within cells. However, the
      ability of this modified transactivator to maintain homogeneous inducibility in
      long-term culture has not been examined. We demonstrate that rtTA2S-M2 expressing
      clones exhibit functional transactivator activity for over 7 months in culture.
      Furthermore, rtTA2S-M2 expressing clones with chromosomally integrated copies of
      a TRE-green fluorescent protein (GFP) reporter also exhibited homogeneous
      inducibility in long-term culture. Importantly, the inherent reduced toxicity and
      improved stability of rtTA2S-M2 obviates the need to continuously select for its
      message, once clones with functional transactivator are isolated. The use of
      rtTA2S-M2 did not, however, preclude clones with stably integrated TRE-reporter
      from exhibiting leakiness. However, inclusion of flanking double copies of a
      'minimal core element' of the chicken beta-globin gene insulator, instead of the
      1.4 kb region, in the TRE-reporter was sufficient to markedly reduce the
      frequency of clones with high basal expression. Inclusion of the insulator core
      also did not affect the maximal expression levels of the inducible gene, which
      typically equaled or exceeded that observed with the strong constitutive CMV
      promoter. Finally, with this system homogeneous inducibility was observed rapidly
      and with low doses of Dox.

PMID- 14960362
TI  - A unique ATG triplet downstream of gene start in archaea: implications for
      translation initiation and evolution.
AB  - Searching for unique features of archaeal genome may shed light on the mechanism
      of gene regulation in primitive life forms. Statistical analysis of ATG frequency
      on the complete genome sequences of 16 archaea, 20 bacteria and 2 eukaryotes
      revealed that most of the archaeal genomes have a remarkably high ATG frequency
      at the position of nine nucleotide (nt) downstream of the translation initiation
      site (the first nucleotide of the translation initiation codon is designated as
      0). To understand the role of this unique ATG in archaea, we further analyzed the
      ATG-initiated genes and non-ATG-initiated genes separately, and the results
      indicated that only the non-ATG-initiated genes contribute to the high ATG
      frequency at position +9. This led us to speculate that the in-frame ATG at +9
      may serve as a remedial initiation site for archaea in case of initiation failure
      at the regular site. In addition, it seems that this phenomenon does not result
      from the harsh environment that archaea are usually viable according to the fact
      that no considerably high ATG frequency at +9 was observed in all the four
      thermophilic bacteria that also live in harsh environment. We proposed that the
      high ATG frequency at position +9 might reflect the decreased efficiency of the
      translation initiation machinery in archaea. Since archaea evolve very slowly,
      this unique characteristic of high ATG frequency at position +9 may present the
      primitive state of the Universal Ancestor.

PMID- 14960363
TI  - CYP4AB1, CYP4AB2, and Gp-9 gene overexpression associated with workers of the red
      imported fire ant, Solenopsis invicta Buren.
AB  - Two cytochrome P450 genes, CYP4AB1 and CYP4AB2, and the Gp-9 gene were identified
      as being specifically overexpressed in workers of the red imported fire ant using
      PCR-selected subtractive hybridization and cDNA array techniques. Full-length
      CYP4AB1 and CYP4AB2 were cloned and sequenced. The cDNA sequences of CYP4AB1 and
      CYP4AB2 have open reading frames of 1389 and 1533 nucleotides encoding proteins
      of 463 and 511 amino acid residues, respectively. Northern blot analysis was
      performed to compare expression levels of CYP4AB1, CYP4AB2, and Gp-9 for
      different developmental stages and castes of fire ants. We demonstrate that the
      expression of these three genes is developmentally and caste specifically
      regulated in red imported fire ants. Levels of CYP4AB1 mRNA were undetectable in
      3rd+4th instars, worker pupae, and alate (mixed sex) pupae; readily detectable in
      male and female alates; increased (approximately 3-fold) in the queens; and rose
      to a maximum (13-fold) in workers. Similarly, the expression of CYP4AB2 mRNA was
      undetectable in 3rd+4th instars, worker pupae, and alate pupae; low in male and
      female alates and queens; and increased (approximately 7-fold) in workers. Levels
      of Gp-9 mRNA were readily detectable in male alates; increased (approximately 3
      fold) in female alates; and reached a maximum (approximately 12-fold) in workers.
      Their caste-specific overexpression suggests the functional importance of
      CYP4AB1, CYP4AB2, and Gp-9 in workers of the red imported fire ant.

PMID- 14960364
TI  - Alternative spliced variants of the alpha-methylacyl-CoA racemase gene and their
      expression in prostate cancer.
AB  - Alpha-methyacyl-CoA racemase (AMACR), a mitochondrial and peroxisomal enzyme
      essential in lipid metabolism, is overexpressed in prostate cancer. Two different
      AMACR transcripts (designated IA and IIA), each derived from five exons, have
      been reported. AMACR IA, the most abundant form, encodes a 382-amino acid protein
      (Mw 42 kDa, pI 6.07). AMACR IIA contains an alternative fifth exon that has
      extensive homology to the human fumarate hydratase (FH) and encodes a 288-amino
      acid protein (Mw 32 kDa, pI 9.6). Here we report additional variants of IA and
      IIA whereby the transcripts lack exon 3 and are designated as IB (Mw 22 kDa, pI
      10.31) and IIB (Mw 31 kDa, pI 9.44). Due to a frameshift, the alternative fifth
      exon in the IIA transcript encodes a polypeptide that differs from FH. In
      contrast, the IIB transcript, generated as a result of the dual alternative
      splicing events, encodes a polypeptide homologous with a highly conserved region
      of FH. We also identified a shorter variant form of IIA (IIAs, Mw 28 kDa, pI
      9.65), which lacks the 5' half of the alternative fifth exon. The carboxy termini
      of all five gene products differ as a result of the alternative splicing events.
      In prostate tumor tissues that overexpressed AMACR, both the A and B forms were
      overexpressed, suggesting coregulation. Only the predominant AMACR IA has an
      acidic pI and contains the previously identified peroxisomal targeting signal
      (PTS1) peptide, while the other four variants are basic proteins that lack the
      peroxisomal targeting signal peptide. These observations have implications for
      the cellular localization and function of these AMACR variants.

PMID- 14960365
TI  - Identification of a novel box C/D snoRNA from mouse nucleolar cDNA library.
AB  - By construction and screen of mouse nucleolar cDNA library, a novel mammalian
      small nucleolar RNAs (snoRNA) was identified. The novel snoRNA, 70 nt in length,
      displays structural features typical of C/D box snoRNA family. The snoRNA
      possesses an 11-nt-long rRNA antisense element and is predicted to guide the 2'-O
      methylation of mouse 28S rRNA at G4043, a site unknown so far to be modified in
      vertebrates. The comparison of functional element of snoRNA guides among
      eukaryotes reveals that the novel snoRNA is a mammalian counterpart of yeast
      snR38 despite highly divergent sequence between them. Mouse and human snR38 and
      other cognates in distant vertebrates were positively detected with slight length
      variability. As expected, the rRNA ribose-methylation site predicted by mouse
      snR38 was precisely mapped by specific-primer extension assay. Furthermore, our
      analyses show that mouse and human snR38 gene have multiple variants and are
      nested in the introns of different host genes with unknown function. Thus, snR38
      is a phylogenetically conserved methylation guide but exhibits different genomic
      organization in eukaryotes.

PMID- 14960366
TI  - Structure and expression of the ovine Hoxc-13 gene.
AB  - HOXC-13 has an important role in controlling hair formation through regulating
      keratin differentiation-specific genes. In this study, we describe the isolation
      and characterisation of the Hoxc-13 gene from sheep wool follicles and its
      expression in the skin. We show that the gene organisation of ovine Hoxc-13 is
      similar to other homeobox genes of the Abd-B type I Homeobox class with two exons
      split by an intron next to the homeobox. The gene spans 7.5 kilobases (kb) and
      has a relatively large intron, which divides an open reading frame of 2361
      nucleotides. The predicted ovine Hoxc-13 protein of 330 amino acids has over 97%
      sequence identity with the human and mouse proteins. A second novel transcript
      was identified, which could produce a truncated Hoxc-13 protein lacking 15 amino
      acids from the N-terminus. A positionally conserved Hoxc-13 binding site in the
      Hoxc-13 proximal promoters of sheep, human, mouse and newt suggests that Hoxc-13
      expression is autoregulatory. Positionally conserved motifs for LEF-1 and
      Whn/Foxn1 suggest that Hoxc-13 may be a downstream target of these transcription
      factors known to regulate hair growth. In addition to expression in the follicle,
      we detected Hoxc-13 in cells of the blood sinus surrounding vibrissal follicles
      and in scattered cells in the upper dermis of the skin. Thus, in addition to a
      role in controlling transcription of hair keratins, Hoxc-13 may have other roles
      in skin function.

PMID- 14960367
TI  - "Plus-C" odorant-binding protein genes in two Drosophila species and the malaria
      mosquito Anopheles gambiae.
AB  - Olfaction plays a crucial role in many aspects of insect behaviour, including
      host selection by agricultural pests and vectors of human disease. Insect odorant
      binding proteins (OBPs) are thought to function as the first step in molecular
      recognition and the transport of semiochemicals. The whole genome sequence of the
      fruit fly Drosophila melanogaster has been completed and a large number of genes
      have been annotated as OBPs, based on the presence of six conserved cysteine
      residues and a conserved spacing between the cysteines. These proteins can be
      divided into three distinct subgroups; those with only one six-cysteine motif,
      those with two such motifs and those with one motif, three extra conserved
      cysteines and a conserved proline immediately after the sixth cysteine. This
      study concentrates on the last two subgroups, referred to as 'dimer' OBPs and
      'Plus-C' OBPs, respectively. We determined the tissue-specific transcript levels
      of all of these OBP genes of D. melanogaster using semiquantitative RT-PCR. The
      results showed that the expression patterns can vary within a subgroup of genes
      and that this technique is valuable for assessing which of the putative OBP genes
      are likely to be involved in Drosophila olfaction. The publicly available genomes
      of another fruit fly Drosophila pseudoobscura, the malaria mosquito Anopheles
      gambiae and the yellow fever mosquito Aedes aegypti were searched by Blast
      against each Plus-C OBP and dimer OBP of D. melanogaster. Related genes were
      found in all of the other species and the relationships of these with the D.
      melanogaster genes and their possible biological functions are discussed.

PMID- 14960368
TI  - Complete mitochondrial DNA sequence of the sea-firefly, Vargula hilgendorfii
      (Crustacea, Ostracoda) with duplicate control regions.
AB  - The primary structure of the mitochondrial genome of the bioluminescent
      crustacean, Vargula hilgendorfii, the sea-firefly (Arthropoda, Crustacea,
      Ostracoda), has sequenced using the transposon Tn5. The genome (15,923 bp)
      contains the same 37 genes (two ribosomal RNAs, 22 transfer RNAs, and 13 protein
      coding genes) found in other Arthropoda. Interestingly, duplicate control regions
      (fragments of 778 and 855 bp) and triplicate short repeat sequences (fragments of
      49 bp) occur. The AT composition of the protein-coding genes is lower than the
      published complete mitochondrial genomes within the Arthropoda. For gene
      arrangement, 13 transfer RNA genes and two protein-coding genes have moved and
      inserted directly or inversely relative to the typical Arthropoda order.

PMID- 14960369
TI  - The third man and the fourth paper.

PMID- 14960370
TI  - Heterogeneous nanostructural and nanoelastic properties of pericellular and
      interterritorial matrices of chondrocytes by atomic force microscopy.
AB  - Hyaline cartilage consists of sparse chondrocytes and abundant extracellular
      matrix. There is a paucity of experimental data in support of the notion of
      conceivable regional differences in the mechanical properties of chondral
      matrices. Upon visual differentiation of the pericellular and interterritorial
      matrices in each of 19 fresh growth plate samples with toluidine blue and
      alizarin red labels, nanoindentation was applied separately to the pericellular
      matrix and interterritorial matrix to using fluid-phase atomic force microscopy
      and real-time imaging. The interterritorial matrix demonstrated elongated
      parallel ridges, whereas the pericellular matrix showed irregular, short-range
      elevations with characteristic pores and canals. Analysis of surface contours at
      600nm(2) scan size revealed that the interterritorial matrix had significantly
      greater surface roughness (71+/-18nm; mean+/-SE) than the pericellular matrix
      (24+/-4nm) ( P< 0.001). The average Young's modulus of the interterritorial
      matrix was 636+/-123 (kPa), significantly greater than the pericellular matrix
      (265+/-53kPa) (P< 0.001 ). Thus, the interterritorial matrix appears to possess
      not only distinct microtopographic contours in comparison with the pericellular
      matrix, but also significantly greater mechanical stiffness. These distinctive
      nanostructural and nanomechanical properties may have implications in nutrient
      diffusion and fluid dynamics, both of which are of vital importance for cartilage
      health and function.

PMID- 14960371
TI  - Model structures of the N-methyl-D-aspartate receptor subunit NR1 explain the
      molecular recognition of agonist and antagonist ligands.
AB  - Molecular models of the ligand-binding domain of N-methyl-d-aspartate subunit R1
      (NR1) were made using the published crystal structures of rat glutamate receptor
      B (GluRB), the bacterial glutamate receptor (GluR0), and the glutamine-binding
      protein (QBP) of Escherichia coli. Separate models of NR1 were built to represent
      the ligand-binding conformation for agonist (glycine, d- and l-isomers of serine
      and alanine, and the partial agonist ligand d-cycloserine) and antagonist (5,7
      dichloro-4-oxo-1,4-dihydroquinoline-2-carboxylic acid (DCKA) and E-3-(2-phenyl-2
      carboxyethenyl)-4,6-dichloro-1-H-indole-2-carboxylic acid (MDL 105,519)) ligands.
      Side-chain conformations of residues within the NR1 ligand-binding site were
      selected that optimized the hydrophobic packing and hydrogen bonding among
      residues, while taking into account published data comparing receptor mutants
      with wild-type NR1. Ligands docked to the model structures provide a rational
      explanation for the observed differences in binding affinity and receptor
      activation among agonist and antagonist ligands. NR1 prefers smaller ligands
      (glycine, serine, and alanine) in comparison with GluRB and GluR0 that bind l
      glutamate: the bulky side chain of W731 in NR1 dramatically reduces the size of
      the ligand-binding site, functioning to selectively restrict recognition to
      glycine and the d-isomers of serine and alanine. Nevertheless, many of the
      interactions seen for ligands bound to GluRB, GluR0, and periplasmic-binding
      proteins are present for the ligands docked to the model structures of NR1.

PMID- 14960372
TI  - Ultrastructure of acidic polysaccharides from the cell walls of brown algae.
AB  - We have studied the ultrastructure of acidic polysaccharides from the cell walls
      of brown algae using a variety of electron microscopy techniques. Polysaccharides
      from Padina gymnospora present self assembled structures, forming trabecular
      patterns. Purified fractions constituted by alginic acid and sulfated fucan also
      form well-organized ultrastructures, but the pattern of organization varies
      depending on the polysaccharide species. Alginic acid presents sponge-like
      structures. Sulfated fucan exhibits particles with polygonal forms with a
      polycrystalline structure. These particles are in fact constituted by sulfated
      fucan molecules since they are recognized by a lectin specific for alpha-l
      fucosyl residues. X-ray microanalysis reveal that S is a constituent element, as
      expected for sulfated groups. Finally, an exhaustive purified sulfated fucan
      shows the same ultrastructure formed by polygonal forms. Furthermore, elemental
      analyses of acidic polysaccharides indicate that they retain Zn, when algae were
      collected from a contaminated area. This observation is supported by direct
      quantification of heavy metal in the biomass and also in the solubilized
      polysaccharides compared with the algae from a non-contaminated site. We conclude
      that these molecules have specific ultrastructure and elemental composition; and
      act as metal binder for the nucleation and precipitation of heavy metals when the
      algae are exposed to a metal contaminated environment.

PMID- 14960373
TI  - Amyloid fibrillogenesis of silkmoth chorion protein peptide-analogues via a
      liquid-crystalline intermediate phase.
AB  - Chorion, the major component of silkmoth eggshell, consists of the A and B
      classes of low-molecular weight structural proteins. Chorion protects the oocyte
      and the developing embryo from environmental hazards and this is due to the
      extraordinary physical and chemical properties of its constituent proteins. We
      have shown previously [FEBS Lett. 479 (2000) 141; 499 (2001) 268] that peptide
      analogues of the A and B classes of chorion proteins form amyloid fibrils under a
      variety of conditions, which led us to propose that silkmoth chorion is a
      natural, protective amyloid. In this work, we present data showing conclusively
      that, the first main step of amyloid-like fibrillogenesis of chorion peptides is
      the formation of nuclei of liquid crystalline nature, which is reminiscent of
      spider-silk formation. We show that these liquid-crystalline nuclei (spherulites)
      'collapse'/deteriorate to form amyloid fibrils in a spectacular manner,
      important, it seems, for chorion morphogenesis and amyloid fibrillogenesis in
      general. The molecular 'switch' causing this spectacular transformation is, most
      probably, a conformational transition to the structure of chorion peptides, from
      a left-handed parallel beta-helix to an antiparallel beta-pleated sheet.
      Apparently, these peptides were suitably designed to play this role, after
      millions of years of molecular evolution.

PMID- 14960374
TI  - Hierarchical structural comparisons of bones from wild-type and liliput(dtc232)
      gene-mutated Zebrafish.
AB  - The alterations of hierarchical structures of bone by gene mutation in the
      zebrafish, which is associated with abnormal bone mineralization and bone
      disease, were reported for the first time in this paper. Bone samples from the
      liliput(dtc232) (lil) mutants as well as normal controls were studied by
      polarized light microscope, scanning electron microscope (SEM), transmission
      electron microscope (TEM), and atomic force microscope (AFM). Light microscopy
      examinations reveal that the lil bone has asymmetric mineralization and much
      thinner bone wall. The SEM studies show a lot of microcracks in lil bone wall.
      And the plywood-like structure of the normal bone does not exist in the lil bone,
      which is confirmed by the measurements of polarized light microscope.
      Furthermore, the TEM investigations display the collagen fibrils with two typical
      diameters. For the thinner collagen fibrils, the diameter of lil bone is about
      twice larger than that of the wild-type bone. And for the thicker one, there is a
      small increase in diameter after mutation and the band periodicity of the lil
      bone is similar with that of wild-type bone, which is consistent with the result
      of AFM. The morphologies of the minerals revealed that the mutated mineral was in
      bigger size and the shape was irregular but not plate-shaped.

PMID- 14960375
TI  - Glycopolymer charge density determines conformation in human ocular mucin gene
      products: an atomic force microscope study.
AB  - Atomic force microscopy (AFM) has been applied to the study of heterogeneity in
      the structure and function of individual biopolymers with complex structures such
      as glycoproteins, polysaccharides and nucleic acids. In this work we describe
      experiments which shed light on the heterogeneity of human ocular mucin gene
      products. By separating samples of native human ocular mucins on a caesium
      chloride density gradient, at least three populations consisting predominantly of
      products of the gene MUC5AC can be identified. Separation on the caesium chloride
      density gradient is governed by molecular architecture and charge density, and
      thus provides a route to the discrimination between different glycoforms within a
      glycoprotein sample. AFM images of these populations show that each is
      characterised by different conformational properties and polymer diameters, both
      of which can be attributed to differences in the degree and nature of
      glycosylation. These differences in glycosylation are likely to be the result of
      post-translational processing and may also have functional consequences. The
      AFM's ability to examine the composition of a predominantly single gene product
      population at the level of the single molecule allows the consequences of post
      translational process heterogeneity to be examined at high resolution.

PMID- 14960376
TI  - Cell organization and ultrastructure of a magnetotactic multicellular organism.
AB  - Magnetotactic multicellular aggregates and many-celled magnetotactic prokaryotes
      have been described as spherical organisms composed of several Gram-negative
      bacteria capable to align themselves along magnetic fields and swim as a unit.
      Here we describe a similar organism collected in a large hypersaline lagoon in
      Brazil. Ultrathin sections and freeze fracture replicas showed that the cells are
      arranged side by side and face both the external environment and an internal
      acellular compartment in the center of the organism. This compartment contains a
      belt of filaments linking the cells, and numerous membrane vesicles. The shape of
      the cells approaches a pyramid, with the apex pointing to the internal
      compartment, and the basis facing the external environment. The contact region of
      two cells is flat and represents the pyramid faces, while the contacts of three
      or more cells contain cell projections and represent the edges. Freeze-fracture
      replicas showed a high concentration of intramembrane particles on the edges and
      also in the region of the outer membrane that faces the external environment.
      Dark field optical microscopy showed that the whole organism performs a
      coordinated movement with either straight or helicoidal trajectories. We conclude
      that the organisms described in this work are, in fact, highly organized
      prokaryotic multicellular organisms.

PMID- 14960377
TI  - Conformational and enzymatic changes of 20S proteasome of rat natural killer
      cells induced by mono- and divalent cations.
AB  - We have been investigated the relation between activation of "neutral" and
      "acidic" chymotrypsin-like (ChT-L) activity and conformational changes in the 20S
      proteasome complex from the rat natural killer (NK) cells induced by SDS, mono-
      and divalent cations. The conformational changes were monitored by tryptophan
      fluorescence and light scattering. It was revealed that the changes in the
      maximum position and contribution of the short-wavelength spectral component
      correlated with the alteration of ChT-L activity of the proteasome. Statistical
      analysis was applied to assign the fluorescence components with tryptophan
      residues based on the classification of calculated structural parameters of the
      environment of tryptophan fluorophores in protein. It was proposed that the
      emission of W13 from alpha6-subunit located near the cluster of highly conserved
      proteasome residues is mostly sensitive to the activation of the enzyme. We
      concluded that the expression of maximal ChT-L activity of 20S proteasome is
      associated with the conformational changes occurs in this cluster that lead to
      the proteasome open conformation, allowing substrate access into the proteolytic
      chamber.

PMID- 14960378
TI  - Yeast nuclear pore complexes have a cytoplasmic ring and internal filaments.
AB  - The nuclear pore complex (NPC) controls transport of macromolecules across the
      nuclear envelope. It is large and complex but appears to consist of only
      approximately 30 different proteins despite its mass of > 60MDa. Vertebrate NPC
      structure has been analyzed by several methods giving a comprehensive
      architectural model. Despite our knowledge of yeast nucleoporins, structural data
      is more limited and suggests the basic organization is similar to vertebrates,
      but may lack some peripheral and other components. Using field emission scanning
      electron microscopy to probe NPC structure we found that the yeast, like higher
      eukaryotic, NPCs contain similar peripheral components. We can detect cytoplasmic
      rings and evidence of nucleoplasmic rings in yeasts. A filamentous basket is
      present on the nucleoplasmic face and evidence for cytoplasmic filaments is
      shown. We observed a central structure, possibly the transporter, that which may
      be linked to the cytoplasmic ring by internal filaments. Immuno-gold labeling
      suggested that Nup159p may be attached to the cytoplasmic ring, whereas Nup116p
      may be associated, partly, with the cytoplasmic filaments. Analysis of a Nup57p
      mutant suggested a role in maintaining the stability of cytoplasmic components of
      the NPC. We conclude that peripheral NPC components appear similar in yeasts
      compared to higher organisms and present a revised model for yeast NPC structural
      composition.

PMID- 14960379
TI  - Structure of the scorpion toxin BmBKTtx1 solved from single wavelength anomalous
      scattering of sulfur.
AB  - This report describes the crystal structure of the K(+) channel-blocking toxin,
      BmBKTx1, isolated recently from the venom of the scorpion Buthus martensi Karsch.
      This is only the second structure of the short-chain K(+) channel-blocking toxin
      from scorpion solved by means of X-ray crystallography. Additionally, reductive
      dimethylation of folded BmBKTx1 employed to induce its crystallization and
      solution of the structure based on the anomalous signal from the sulfur atoms
      make this example quite unique. The monomer of BmBKTx1 is formed by 31 amino acid
      residues, including 6 cysteines connected in 3 disulfide bridges. Crystals of
      this toxin belong to the space group P2(1) with two molecules present in the
      asymmetric unit. The unit cell parameters are a = 21.40 A, b=39.70 A, c=29.37 A,
      and beta-94.13 grades. Based on the high-quality dataset (anomalous signal)
      collected to the resolution 1.72A using the conventional X-radiation generator
      (lambda Cu, K alpha = 1.5478 A), the positions of sulfur atoms contributed by 12
      cysteine residues have been identified, and subsequent improvement of the
      experimental phases have allowed structure solution. The final model was refined
      to the crystallographic R-factor of 0.166. The methyl groups on several lysine
      residues could be easily modeled into the electron density.

PMID- 14960380
TI  - Structural analysis of DNA-PKcs: modelling of the repeat units and insights into
      the detailed molecular architecture.
AB  - DNA-dependent protein kinase (DNA-PK) is part of the eukaryotic DNA double strand
      break repair pathway and as such is crucial for maintenance of genomic stability,
      as well as for V(D)J (variable-diversity-joining) recombination. The catalytic
      subunit of DNA-PK (DNA-PKcs) belongs to the phosphatidylinositol-3 (PI-3) kinase
      like kinase (PIKK) superfamily and is comprised of approximately 4100 amino
      acids. We have used a novel repeat detection method to analyse this enormous
      protein and have identified two different types of helical repeat motifs in the N
      terminal region of the sequence, as well as other previously unreported features
      in this repeat region. A comparison with the ATMs, ATRs, and TORs show that the
      features identified are likely to be conserved throughout the PIKK superfamily.
      Homology modelling of parts of the DNA-PKcs sequence has been undertaken and we
      have been able to fit the models to previously obtained electron microscopy data.
      This work provides an insight into the overall architecture of the DNA-PKcs
      protein and identifies regions of interest for further experimental studies.

PMID- 14960385
TI  - How to show that an ineffective therapy works.

PMID- 14960386
TI  - Advancing in the face of conventional wisdom.

PMID- 14960387
TI  - Dendrimers and protein cages as nanoparticles in drug delivery.

PMID- 14960388
TI  - Oligonucleotides make sensible strides.

PMID- 14960389
TI  - The multiple orthogonal tools approach to define molecular causation in the
      validation of druggable targets.
AB  - Many genetic (gene deletion, interruption or mutation), epigenetic (such as
      antisense or small interfering RNA) and immunological methods are being applied
      in 'high-throughput target validation' studies of the novel potential targets
      arising from whole genome sequencing. Such applications often focus on 'loss of
      function' approaches. However, target validation is most reliable when multiple
      orthogonal approaches are used. Initiating a target-based discovery project based
      on correlative evidence is faster than awaiting causative evidence. Indeed, the
      multiple tools needed to generate firm proof usually include methods and reagents
      only generated after starting a discovery project with little evidence beyond
      correlations. Robust and rigorous tests of whether a drug candidate is
      efficacious in vivo because of its effects on a specific molecular particular
      target are best made by simultaneously applying multiple orthogonal tools.
      Examples of the orthogonal tools approach will be discussed.

PMID- 14960390
TI  - Early prediction of drug metabolism and toxicity: systems biology approach and
      modeling.
AB  - Many of the drug candidates that fail in clinical trials are withdrawn because of
      unforeseen effects of human metabolism, such as toxicity and unfavorable
      pharmacokinetic profiles. Early pre-clinical elimination of such compounds is
      important but not yet possible. An ideal system would enable researchers to make
      a confident elimination decision based purely on the structure of a new compound,
      and incorporate and use multiple pre-clinical experimental data to support such a
      decision. Currently available resources can be split into three categories: (i).
      structure-activity relationships (SAR) computational models based on compound
      structure; (ii). 'pattern' databases of tissue or organ response to drugs,
      compiled from high-throughput experiments; and (iii). 'systems biology' databases
      of metabolic pathways, genes and regulatory networks. In this review, we outline
      the advantages and drawbacks of each of these systems and suggest directions for
      their integration.

PMID- 14960391
TI  - Multidimensional separations in the pharmaceutical arena.
AB  - The introduction of novel, powerful and rapid multidimensional separation and
      characterization methods has produced revolutionary global changes at the genome,
      proteome and metabolome level, bringing about a radical transition in our views
      of living systems, at the molecular level. The age of proteomics and metabolomics
      demands high-resolution multidimensional separation techniques. Multidimensional
      gas and liquid chromatography techniques, in addition to capillary and microchip
      electrophoresis methods, offer increased resolution and sensitivity, while also
      affording adequate throughput and reproducibility to meet the demands of the
      modern pharmaceutical industry. Coupled with MS, these techniques provide not
      only separation but also reliable identification of the sample components. The
      resolving power of these methods has proved to be superior over individual one
      dimensional approaches, enabling the comprehensive separation of complex
      biological mixtures, with excellent resolution and reproducibility. High capacity
      computer systems that are capable of rigorous qualitative and quantitative
      analysis of the separation profiles allow the establishment and mining of large
      databases. Examples of various modern multidimensional separation techniques, and
      their integration with MS, are reviewed, here, with respect to pharmaceutical
      analysis.

PMID- 14960392
TI  - Pharmaceutical companies liable for fraudulent research by subcontractors.

PMID- 14960393
TI  - Robin Ganellin gives his views on medicinal chemistry and drug discovery.
      Interview by Stephen L. Carney.
AB  - Robin Ganellin was born in East London and studied chemistry at Queen Mary
      College, London, receiving a PhD in 1958 under Professor Michael Dewar for his
      research on tropylium chemistry. He joined Smith Kline & French Laboratories
      (SK&F) in the UK in 1958 and was one of the co-inventors of the revolutionary
      drug cimetidine (Tagamet(R)) He subsequently became Vice-President for Research
      at the company's Welwyn facility. In 1986 he was awarded a DSc from London
      University for his work on the medicinal chemistry of drugs acting at histamine
      receptors and was also made a Fellow of the Royal Society and appointed to the
      SK&F Chair of Medicinal Chemistry at University College London, where he is now
      Emeritus Professor of Medicinal Chemistry. Professor Ganellin has been honoured
      extensively, including such awards as the Royal Society of Chemistry Award for
      Medicinal Chemistry, their Tilden Medal and Lectureship and their Adrien Albert
      Medal and Lectureship, Le Prix Charles Mentzer de France, the ACS Division of
      Medicinal Chemistry Award, the Society of Chemical Industry Messel Medal and the
      Society for Drug Research Award for Drug Discovery. He is a past Chairman of the
      Society for Drug Research, was President of the Medicinal Chemistry Section of
      IUPAC, and is currently Chairman of the IUPAC Subcommittee on Medicinal Chemistry
      and Drug Development.

PMID- 14960394
TI  - Prediction of blood-brain barrier penetration: are we missing the point?

PMID- 14960395
TI  - Stacking up the armory against viruses.

PMID- 14960396
TI  - Biological basis for the benefit of nutraceutical supplementation in arthritis.
AB  - Arthritis is a common disease in which the end-point results in joint replacement
      surgery. This article reviews the use of nutraceuticals as alternative treatments
      for pathological manifestations of arthritic disease. The efficacy of fish oils
      (e.g. cod liver oil) in the diet has been demonstrated in several clinical
      trials, animal feeding experiments and in vitro models that mimic cartilage
      destruction in arthritic disease. In addition, there is some evidence for
      beneficial effects of other nutraceuticals, such as green tea, herbal extracts,
      chondroitin sulphate and glucosamine. However, in most cases, there is little
      scientific evidence at the cellular and molecular levels to explain their
      mechanisms of action.

PMID- 14960397
TI  - Analysis, statistical validation and dissemination of large-scale proteomics
      datasets generated by tandem MS.
AB  - Tandem mass spectrometry has been used increasingly for high-throughput analysis
      of complex protein samples. A major challenge lies in the consistent, objective
      and transparent analysis of the large amounts of data generated by such
      experiments and in their dissemination and publication. Here, we review currently
      available computational tools and discuss the need for statistical criteria in
      the analysis of large proteomics datasets.

PMID- 14960398
TI  - High-throughput molecular pathology in human tissues as a method for driving drug
      discovery.
AB  - To facilitate prioritization of potential drug targets, gene expression can be
      localized to individual cell types in normal and diseased tissues. Given the
      complexity of molecular physiology and pathology, the creation of large-scale
      molecular pathology databases collating data obtained from human tissues is a
      challenging marriage of old and new technologies, particularly when considering
      the many issues that preclude easy access to substantial quantities of human
      tissues. Molecular pathology databases are powerful tools and are essential for
      early-stage drug discovery, enabling informed decisions to be made with respect
      to scientific direction and follow-up research.

PMID- 14960400
TI  - Forty years of diffusion of innovations: utility and value in public health.
AB  - This special issue is created to mark the 40th anniversary of Everett Rogers'
      Diffusion of Innovations (DOI) model. Diffusion is the process through which an
      innovation, defined as an idea perceived as new, spreads via certain
      communication channels over time among the members of a particular social system.
      A great deal of research in a variety of academic disciplines (about 5000
      published studies so far) has been conducted on the diffusion of innovations over
      the past six decades. The areas of application for these studies range from
      hybrid seed corn to modern math, to the snowmobile to antibiotic drugs, to
      HIV/AIDS prevention (Rogers, 1995). These investigations have led to a general
      model of the diffusion of innovations, which can be applied to the recent spread
      of the Internet or to any other new idea. Everett Roger's ground-breaking model
      has contributed to a greater understanding of behavioral change, including the
      variation in rates of adoption of innovations, and it has held a broad scope of
      practical applications in the field of public health.

PMID- 14960401
TI  - A prospective and retrospective look at the diffusion model.
AB  - In this article we discuss how the diffusion model originally was created, some
      of the most important ways in which it has evolved over the past 30 years, and
      its future prospects.

PMID- 14960402
TI  - Improving the state of health programming by using diffusion theory.
AB  - Year by year, the gaps between what is known about behavior change and what is
      actually practiced in social programs grow larger, especially for community-based
      programs intended to help minority populations, the poor, and those living in
      inner-city and rural areas. Internationally, such gaps between the state of
      knowledge and the state of practice lead to disparities in health, education, and
      development among societal groups, demographic sub-populations, communities, and
      countries. Data about disparities are used as evidence of inequality. Here, I
      discuss uses of certain diffusion of innovation theory-based concepts to
      systematically redress problems of inequality and disparity by reducing the
      differences between evidence and practice in social programs that are implemented
      by intermediaries (practitioners) and communicated by them to needy populations.
      The emphasis here is on the integrated application of knowledge about innovation
      attributes, opinion leadership, and clustering from diffusion theory to achieve
      the objective of more extensive and more rapid diffusion of especially effective
      programs. A set of implementation steps are offered for researchers, funders of
      international health programs, and the intermediaries who implement health
      programs.

PMID- 14960403
TI  - From innovation to social norm: bounded normative influence.
AB  - CORRECTION: Every innovation begins as a deviation from existing social norms.
      Given the strong effect of social norms and pressure, how can any innovation ever
      diffuse to the point where it becomes a new social norm? The seeming paradox of
      how a minority can influence the majority has not been explained well by
      prevailing social science theory. Computer simulations of the diffusion of a new
      behavior within the social network of a Bangladesh village led to the discovery
      of a new principle of social change that resolves this paradox. The results
      revealed the important but overlooked role played by boundaries that emerge
      within a social network and how such local boundaries affect the creation of a
      new social norm. A minority position can become the social norm by means of the
      process of bounded normative influence. As long as a minority maintains its
      majority status within its own, locally bounded portion of the network, then it
      can survive, recruit converts in the near surround, and establish its behavior as
      the norm for the network as a whole. The process is accelerated when the minority
      subgroup is centrally located in the network and communicates more frequently and
      persuasively than the majority.

PMID- 14960404
TI  - Diffusion methodology: time to innovate?
AB  - Over the past 60 years, thousands of diffusion studies have been conducted in
      numerous disciplines of study including sociology, education, communication,
      marketing, and pubic health. With few exceptions, these studies have been driven
      by a methodological approach that has become institutionalized in diffusion
      research. This approach is characterized by the collection of quantitative data
      about one innovation gathered from adopters at a single point in time after
      widespread diffusion has occurred. This dominant approach is examined here in
      terms of both its strengths and weaknesses and with regard to its contribution to
      the collective base of understanding the diffusion of innovations. Alternative
      methodological approaches are proposed and reviewed with consideration for the
      means by which they may expand the knowledge base.

PMID- 14960405
TI  - A meta-analysis of the effect of mediated health communication campaigns on
      behavior change in the United States.
AB  - A meta-analysis was performed of studies of mediated health campaigns in the
      United States in order to examine the effects of the campaigns on behavior
      change. Mediated health campaigns have small measurable effects in the short
      term. Campaign effect sizes varied by the type of behavior: r=.15 for seat belt
      use, r=.13 for oral health, r=.09 for alcohol use reduction, r=.05 for heart
      disease prevention, r=.05 for smoking, r=.04 for mammography and cervical cancer
      screening, and r=.04 for sexual behaviors. Campaigns with an enforcement
      component were more effective than those without. To predict campaign effect
      sizes for topics other than those listed above, researchers can take into account
      whether the behavior in a cessation campaign was addictive, and whether the
      campaign promoted the commencement of a new behavior, versus cessation of an old
      behavior, or prevention of a new undesirable behavior. Given the small campaign
      effect sizes, campaign planners should set modest goals for future campaigns. The
      results can also be useful to evaluators as a benchmark for campaign effects and
      to help estimate necessary sample size.

PMID- 14960406
TI  - Expanding the reach of health campaigns: community organizations as meta-channels
      for the dissemination of health information.
AB  - This study investigates whether, and to what extent, community organizations can
      serve as viable channels of health information. We use Putnam's (2000) findings
      on social capital to argue that organizations can serve two major functions in
      health campaigns: instrumental (e.g., providing material support) and affinity
      (social support). Through a secondary analysis of data from the Stanford Five
      City Project, we find significant support for our predictions about who joins
      community organizations. Membership in community organizations explains greater
      variance in health outcomes than that explained by general media use, demographic
      indicators, and health-specific media use. Implications for health campaigns are
      discussed.

PMID- 14960407
TI  - Diffusion of innovations and HIV/AIDS.
AB  - As the HIV/AIDS epidemic continues its relentless spread in many parts of the
      world, DOI provides a useful framework for analyzing the difficulties in
      achieving behavior change necessary to reduce HIV rates. The DOI concepts most
      relevant to this question include communication channels, the innovation-decision
      process, homophily, the attributes of the innovation, adopter categories, and
      opinion leaders. The preventive measures needed to halt the transmission of HIV
      constitute a "preventive innovation." This article describes the attributes of
      this preventive innovation in terms of relative advantage, compatibility,
      complexity, trialability, and observability. It reviews studies that incorporated
      DOI into HIV/AIDS behavior change interventions, both in Western countries and in
      the developing world. Finally, it discusses possible reasons that the use of DOI
      has been fairly limited to date in HIV/AIDS prevention interventions in
      developing countries.

PMID- 14960408
TI  - Diffusion of innovations: family planning in developing countries.
AB  - One of the best examples of the validity of the theory of "diffusion of
      innovations" is the case of family planning in developing countries. The desire
      of health, development and environment advocates in rich countries to make modern
      contraceptive use and lower fertility a norm in developing countries was
      translated into organized efforts to reach top-level leaders in these countries.
      Once on board, these high-level leaders cooperated with bilateral and
      international funding agencies as well as private foundations to develop mass
      media and community education campaigns, while simultaneously setting up clinic
      infrastructure; training doctors, nurses and outreach workers; and developing a
      new and varied "cafeteria" of modern methods. Over the intervening decades, this
      innovation was indeed diffused and became a norm, but not without its
      controversies and missed opportunities.

PMID- 14960409
TI  - Diffusion of innovations: a world tour.
AB  - This contribution to the 40th Anniversary celebration of the Diffusion of
      Innovations Theory discusses three health communication projects which applied
      the tenets of Diffusion of Innovation Theory with differing results: Using voodoo
      practitioners to pave the way for HIV/AIDS education in Haiti. A food-based
      approach to improving Vitamin A nutrition in Nepal. Diffusion at the horizon of
      life: The difficulties of communicating reproductive health to youth in Mali. The
      article illustrates a spectrum of circumstances in which diffusion theory has
      been applied, in order to show the application of the theory with different
      populations or target groups, in different sectors, and in different regions of
      the world.

PMID- 14960410
TI  - Ev Rogers: helping to build a modern synthesis of social change.

PMID- 14960411
TI  - Some reflections on diffusion theory and the role of Everett Rogers.

PMID- 14960412
TI  - Everett Rogers' diffusion of innovations theory: its utility and value in public
      health.

PMID- 14960413
TI  - Isolation of nuclei from label-retaining cells and measurement of their turnover
      rates in rat colon.
AB  - We describe here a new technique for isolating nuclei from long-term label
      retaining cells (LRCs), a subpopulation enriched with stem cells from colon, and
      for measuring their proliferation rates in vivo. A double-label approach was
      developed, combining the use of bromodeoxyuridine (BrdU) and (2)H(2)O. Male
      Fisher 344 rats were administered BrdU in drinking water continuously for 2-8 wk.
      BrdU was then discontinued (BrdU washout), and animals (n = 33) were switched to
      (2)H(2)O in drinking water and killed after 2, 4, and 8 wk. Nuclei from BrdU
      positive cells (LRCs) were collected by flow cytometry. The percentages of LRCs
      were 7 and 3.8% after 4 and 8 wk of BrdU washout, respectively. Turnover rates of
      LRCs were measured on the basis of deuterium incorporation from (2)H(2)O into DNA
      of LRC nuclei, as determined by mass spectrometry. The proliferation rate of the
      LRCs collected was 0.33-0.90% per day (half-life of 77-210 days). Significant
      contamination from other potentially long-lived colon cells was excluded. In
      conclusion, this double-labeling method allows both physical isolation of nuclei
      from colon epithelial LRCs and measurement of their in vivo proliferation rates.
      Use of this approach may allow better understanding of mechanisms by which agents
      induce or protect against colon carcinogenesis.

PMID- 14960414
TI  - Characterization of in vitro gutlike organ formed from mouse embryonic stem
      cells.
AB  - Using an embryoid body (EB) culture system, we have made a functional organlike
      cluster: the "gut" from embryonic stem (ES) cells (ES gut). There are many types
      of ES clusters, because ES cells have a pluripotent ability to develop into a
      wide range of cell types. Before inducing specific differentiation by exogenously
      added factors, we characterized comprehensive physiological and morphological
      properties of ES guts. Each ES gut has a hemispherical (or cystic) structure and
      exhibits spontaneous contractions [mean frequency: 13.5 +/- 8.8 cycles per min
      (cpm)]. A dense distribution of interstitial cells of Cajal (ICC) was identified
      by c-Kit immunoreactivity, and specific subcellular structures of ICC and smooth
      muscle cells were identified with electron microscopy. ICC frequently formed
      close contacts with the neighboring smooth muscle cells and occasionally formed
      gap junctions with other ICC. Widely propagating intracellular Ca(2+)
      concentration oscillations were generated in the ES gut from the aggregates of c
      Kit immunopositive cells. Plateau potentials, possibly pacemaker potentials in
      ICC, and electrical slow waves were recorded for the first time. These events
      were nifedipine insensitive, as in the mouse gut. Our present results indicate
      that the rhythmic pacemaker activity generated in ICC efficiently spreads to
      smooth muscle cells and drives spontaneous rhythmic contractions of the ES gut.
      The present characterization of physiological and morphological properties of ES
      gut paves the way for making appropriate models to investigate the origin of
      rhythmicity in the gut.

PMID- 14960415
TI  - MEF2 activation in differentiated primary human skeletal muscle cultures requires
      coordinated involvement of parallel pathways.
AB  - The myocyte enhancer factor (MEF)2 transcription factor is important for
      development of differentiated skeletal muscle. We investigated the regulation of
      MEF2 DNA binding in differentiated primary human skeletal muscle cells and
      isolated rat skeletal muscle after exposure to various stimuli. MEF2 DNA binding
      activity in nonstimulated (basal) muscle cultures was almost undetectable.
      Exposure of cells for 20 min to 120 nM insulin, 0.1 and 1.0 mM hydrogen peroxide,
      osmotic stress (400 mM mannitol), or 1.0 mM 5-aminoimidazole-4-carboxamide-1-beta
      D-ribofuranoside (AICAR) led to a profound increase in MEF2 DNA binding. To study
      signaling pathways mediating MEF2 activity, we preincubated human skeletal muscle
      cell cultures or isolated rat epitrochlearis muscles with inhibitors of p38
      mitogen-activated protein kinase (MAPK) (10 microM SB-203580), MEK1 (50 microM PD
      98059), PKC (1 and 10 microM GF109203X), phosphatidylinositol (PI) 3-kinase (10
      microM LY-294002), or AMP-activated protein kinase (AMPK; 20 microM compound C).
      All stimuli resulted primarily in activation of MEF2D DNA binding. Exposure of
      cells to osmotic or oxidative stress increased MEF2 DNA binding via pathways that
      were completely blocked by MAPK inhibitors and partially blocked by inhibitors of
      PKC, PI 3-kinase, and AMPK. In epitrochlearis muscle, MAPK inhibitors blocked
      contraction but not AICAR-mediated MEF2 DNA binding. Thus activation of MEF2 in
      skeletal muscle is regulated via parallel intracellular signaling pathways in
      response to insulin, cellular stress, or activation of AMPK.

PMID- 14960416
TI  - Osmotic swelling-provoked release of organic osmolytes in human intestinal
      epithelial cells.
AB  - Human Intestine 407 cells respond to osmotic cell swelling by the activation of
      Cl(-)- and K(+)-selective ionic channels, as well as by stimulating an organic
      osmolyte release pathway readily permeable to taurine and phosphocholine. Unlike
      the activation of volume-regulated anion channels (VRAC), activation of the
      organic osmolyte release pathway shows a lag time of approximately 30-60 s, and
      its activity persists for at least 8-12 min. In contrast to VRAC activation,
      stimulation of organic osmolyte release did not require protein tyrosine
      phosphorylation, active p21(rho), or phosphatidylinositol 3-kinase activity and
      was insensitive to Cl(-) channel blockers. Treatment of the cells with putative
      organic anion transporter inhibitors reduced the release of taurine only
      partially or was found to be ineffective. The efflux was blocked by a subclass of
      organic cation transporter (OCT) inhibitors (cyanine-863 and decynium-22) but not
      by other OCT inhibitors (cimetidine, quinine, and verapamil). Brief treatment of
      the cells with phorbol esters potentiated the cell swelling-induced taurine
      efflux, whereas addition of the protein kinase C (PKC) inhibitor GF109203X
      largely inhibited the response, suggesting that PKC is involved. Increasing the
      level of intracellular Ca(2+) by using A-23187- or Ca(2+)-mobilizing hormones,
      however, did not affect the magnitude of the response. Taken together, the
      results indicate that the hypotonicity-induced efflux of organic osmolytes is
      independent of VRAC and involves a PKC-dependent step.

PMID- 14960417
TI  - Immunocytochemical localization of Na+-HCO3- cotransporters and carbonic
      anhydrase dependence of fluid transport in corneal endothelial cells.
AB  - In corneal endothelium, there is evidence for basolateral entry of HCO(3)(-) into
      corneal endothelial cells via Na(+)-HCO(3)(-) cotransporter (NBC) proteins and
      for net HCO(3)(-) flux from the basolateral to the apical side. However, how
      HCO(3)(-) exits the cells through the apical membrane is unclear. We determined
      that cultured corneal endothelial cells transport HCO(3)(-) similarly to fresh
      tissue. In addition, Cl(-) channel inhibitors decreased fluid transport by at
      most 16%, and inhibition of membrane-bound carbonic anhydrase IV by benzolamide
      or dextran-bound sulfonamide decreased fluid transport by at most 29%. Therefore,
      more than half of the fluid transport cannot be accounted for by anion transport
      through apical Cl(-) channels, CO(2) diffusion across the apical membrane, or a
      combination of these two mechanisms. However, immunocytochemistry using optical
      sectioning by confocal microscopy and cryosections revealed the presence of NBC
      transporters in both the basolateral and apical cell membranes of cultured bovine
      corneal endothelial cells and freshly isolated rabbit endothelia. This newly
      detected presence of an apical NBC transporter is consistent with its being the
      missing mechanism sought. We discuss discrepancies with other reports and provide
      a model that accounts for the experimental observations by assuming different
      stoichiometries of the NBC transport proteins at the basolateral and apical sides
      of the cells. Such functional differences might arise either from the expression
      of different isoforms or from regulatory factors affecting the stoichiometry of a
      single isoform.

PMID- 14960418
TI  - Care pathways for hip fractures: a useful tool or passing fashion?

PMID- 14960419
TI  - Barriers to delivery of thrombolysis for acute stroke.

PMID- 14960420
TI  - Thrombolysis for stroke in the over 80s.

PMID- 14960421
TI  - Continuing care: legal and 'Coughlan compliant'?

PMID- 14960422
TI  - Older people should NOT be prescribed 'coxibs' in place of conventional NSAIDs.

PMID- 14960423
TI  - Carbon monoxide poisoning: undetected by both patients and their doctors.
AB  - Carbon monoxide poisoning represents a potentially preventable and reversible
      cause of mortality and morbidity if sources and cases can be identified. The
      elderly have been shown to be particularly at risk. Concerns continue to be
      raised about potential unrecognised cases of carbon monoxide poisoning. These
      concerns arise from difficulties in knowing who to suspect as a potential victim
      of poisoning as well as how, when and what to test. In general carbon monoxide
      has no helpful unique clinical presentation and is known to mimic common
      illnesses as well as exacerbate established diseases. As a gas it is undetectable
      by the human senses and is potentially present in most households. This paper
      reviews the issues associated with carbon monoxide poisoning including pointers
      to early diagnosis and discussion of pathophysiology and management.

PMID- 14960424
TI  - A systematic literature review of factors affecting outcome in older medical
      patients admitted to hospital.
AB  - INTRODUCTION: The ACMEplus project aims to devise a standardised system for
      measuring case-mix and outcome in older patients admitted to hospitals in
      different parts of Europe for primarily 'medical' (i.e. not surgical or
      psychiatric) reasons. As a first step in this project, a systematic review was
      carried out to identify factors which had a significant influence on outcome in
      such patients. METHODS: The systematic search used Medline 1966-2000, Cinahl 1982
      2000, Web of Science 1981-2000, reference lists of relevant papers and a hand
      search of Age and Ageing 1974-2000. A six-category grading system was devised to
      classify the 313 identified papers with regard to their relevance to the ACMEplus
      project, study design and power. The analysis of the 14 'category 1' papers is
      presented. RESULTS: The main areas of assessment of case-mix were function,
      cognition, depression, illness severity, nutrition, social elements, aspects of
      diagnosis and demographic details. Statistically significant predictors, for the
      four outcome measures, listed below were: For length of stay: functional status
      score, illness severity, cognitive score, poor nutrition, comorbidity score,
      diagnosis or presenting illness, polypharmacy, age and gender. For mortality:
      functional status score, illness severity, cognitive score, comorbidity score,
      diagnosis or presenting illness, polypharmacy, age and gender. For discharge
      destination: functional status score, cognitive score, diagnosis or presenting
      illness and age. For readmission rate: functional status score, illness severity,
      co-morbidity, polypharmacy, diagnosis or presenting illness and age. CONCLUSIONS:
      Factors affecting outcome in older medical patients are complex. When looking at
      outcomes of hospital admission in older people it is important not just to look
      at routinely available statistics such as age, gender and diagnosis but also to
      take into account multifaceted aspects such as functional status and cognitive
      function.

PMID- 14960425
TI  - A systematic review of barriers to delivery of thrombolysis for acute stroke.
AB  - BACKGROUND AND PURPOSE: Barriers within the patient pathway can prevent early
      administration of thrombolytic therapy in patients admitted with acute stroke.
      This systematic review aimed to identify such barriers that have been reported in
      the medical literature. METHODS: We searched MEDLINE and EMBASE for prospective
      and retrospective observational studies that assessed the nature of barriers to
      delivery of thrombolysis for acute stroke. RESULTS: We identified 54 eligible
      studies (including a total of 39030 patients). The reported barriers included:
      (i). the patient or family did not recognise symptoms of stroke or seek urgent
      help, (ii). the general practitioner (rather than an ambulance) was called first,
      (iii). the paramedics and emergency department staff triaged stroke as non
      urgent, (iv). delays in neuroimaging, (v). inefficient process of in-hospital
      emergency stroke care, (vi). difficulties in obtaining consent for thrombolysis,
      and (vii). physicians' uncertainty about administering thrombolysis. CONCLUSIONS:
      We identified important pre-hospital and in-hospital barriers that should be
      overcome if thrombolysis is to be administered to stroke patients efficiently and
      equitably.

PMID- 14960426
TI  - Risk factors and risk assessment tools for falls in hospital in-patients: a
      systematic review.
AB  - OBJECTIVE: To identify all published papers on risk factors and risk assessment
      tools for falls in hospital inpatients. To identify clinical risk assessment
      tools or individual clinical risk factors predictive of falls, with the ultimate
      aim of informing the design of effective fall prevention strategies. DESIGN:
      Systematic literature review (Cochrane methodology). Independent assessment of
      quality against agreed criteria. Calculation of odds ratios and 95% confidence
      intervals for risk factors and of sensitivity, specificity, negative and positive
      predictive value for risk assessment tools (with odds ratios and confidence
      intervals), where published data sufficient. RESULTS: 28 papers on risk factors
      were identified, with 15 excluded from further analysis. Despite the
      identification of 47 papers purporting to describe falls risk assessment tools,
      only six papers were identified where risk assessment tools had been subjected to
      prospective validation, and only two where validation had been performed in two
      or more patient cohorts. CONCLUSIONS: A small number of significant falls risk
      factors emerged consistently, despite the heterogeneity of settings namely gait
      instability, agitated confusion, urinary incontinence/frequency, falls history
      and prescription of 'culprit' drugs (especially sedative/hypnotics). Simple risk
      assessment tools constructed of similar variables have been shown to predict
      falls with sensitivity and specificity in excess of 70%, although validation in a
      variety of settings and in routine clinical use is lacking. Effective falls
      interventions in this population may require the use of better-validated risk
      assessment tools, or alternatively, attention to common reversible falls risk
      factors in all patients.

PMID- 14960427
TI  - The epidemiology of amyotrophic lateral sclerosis (ALS/MND) in people aged 80 or
      over.
AB  - OBJECTIVE: To describe the clinical features, incidence, survival and process of
      care of people with Amyotrophic Lateral Sclerosis/Motor Neurone Disease aged 80
      years or more at diagnosis. DESIGN: Prospective, population-based descriptive
      epidemiological study. SETTING: Scotland (population 5.1 million), The Scottish
      Motor Neurone Disease Register 1989-1998. PARTICIPANTS: 135 people aged 80 years
      or over at diagnosis. METHODS: Descriptive Epidemiology of Amyotrophic Lateral
      Sclerosis/Motor Neurone Disease in the over 80s. Survival described using Kaplan
      Meier curves. RESULTS: 135 of 1226 cases (11%) were aged 80 years or more. Sixty
      seven (50%) had bulbar onset, and 58 (43%) were men. The standardised incidence
      was 10.2/100000 (95% CI 7.4-13.1) in men and 6.1/100000 (95% CI = 4.3-7.6) in
      women. Median survival from first symptoms was 1.7 years (IQR 1.0-2.8), less than
      younger patients (P = 0.0003; log Rank test). We found evidence of differences in
      the process of care, as older people were less likely to be prescribed Riluzole
      (OR 0.12, 95% CI = 0.02-0.89) or be assessed by a neurologist (OR 0.76, 95% CI =
      0.67-0.86). CONCLUSION: This is the first comprehensive report of the
      epidemiology of Amyotrophic Lateral Sclerosis/Motor Neurone Disease in older
      people. Clinical presentation and survival differ from the population as a whole.
      There is evidence of a different process of care. While this may be to the
      detriment of their survival, this finding would need to be confirmed by further
      prospective studies.

PMID- 14960428
TI  - The use of Chinese herbal medicines and their correlates in Chinese older adults:
      the Singapore Chinese Longitudinal Aging Study.
AB  - BACKGROUND: There are very few studies of the use of Chinese herbal medicine and
      their psychosocial and health-related determinants in older adults. OBJECTIVES:
      To determine the prevalence of use of Chinese herbal medicine in community-living
      Chinese older adults in Singapore and its associations with socio-economic
      status, social support, health behaviour, health and functional status. DESIGN:
      Cross-sectional analyses of baseline data from a longitudinal cohort study of old
      adults (Singapore Chinese Longitudinal Aging Study). SETTING: Community of Toa
      Payoh in Singapore (total population 22800 out of 3 million). PARTICIPANTS:
      community residents comprising 2010 Chinese older adults aged 65 years and above.
      MEASUREMENTS: participants completed a questionnaire on Chinese herbal medicine
      use and other information on psychosocial and health-related variables. RESULTS:
      The use of Chinese herbal medicine over the past year was reported by 25.3% of
      the subjects, among whom 52% reported concurrent use of Western prescription
      medications. Significant factors that were strongly and independently associated
      with Chinese herbal medicine use were limited to extensive social support (OR =
      2.66-5.56), current smoking (OR = 1.35), regular taiqi (OR = 1.94), arthritis (OR
      = 2.36), cancer (OR = 3.15), hypnotic use (OR = 2.08), IADL disability (OR =
      1.72) and poor treatment compliance (OR = 2.35). CONCLUSION: Positive and
      negative psychosocial and health-related factors determine the use of Chinese
      herbal medicine use in Chinese older adults, consistent with the dual-pattern use
      of Chinese herbal medicine as health supplement and complementary/alternative
      medicine.

PMID- 14960429
TI  - Is intravenous recombinant tissue plasminogen activator (rt-PA) safe for use in
      patients over 80 years old with acute ischaemic stroke? - The Calgary experience.
AB  - BACKGROUND: Acute ischaemic stroke is common in older people. There is one
      licensed acute treatment, intravenous recombinant tissue plasminogen activator,
      but little information is available on its safety in over 80 year olds. DESIGN:
      Review of prospectively collected data on 62 consecutive patients, aged 80 years
      and over, treated with recombinant tissue plasminogen activator in a tertiary
      centre. METHODS: Admission demographic data, clinical and CT stroke severity,
      symptomatic haemorrhage rate and other complications were compared between
      patients who were dead at 3 months and those who survived. Discharge location and
      functional scores outcome were reviewed. The results were compared to those of
      other studies. RESULTS: The in-hospital death rate was 24.2% and 3 month
      mortality 32.8%. Patients that died had higher stroke severity scores at
      presentation (NIHSS 20 versus 16, P = 0.04). Six patients (9.7%) suffered
      symptomatic intracranial haemorrhage (SICH), three were classified as fatal
      (4.8%). SICH was significantly associated with death by 3 months (P = 0.02).
      There were no other serious bleeding complications. The SICH rate is similar to
      that from other thrombolytic studies and the mortality rate is similar to the
      natural history of stroke in older populations. CONCLUSION: Older patients have
      high mortality and morbidity from stroke. Older patients should not be excluded
      from recombinant tissue plasminogen activator treatment on the basis of age
      alone.

PMID- 14960430
TI  - Short- and long-term prognosis for very old stroke patients. The Copenhagen
      Stroke Study.
AB  - BACKGROUND AND PURPOSE: The very old are expected to become a growing part of the
      stroke population in the industrialised part of the world. The aims of this study
      were to evaluate clinical characteristics of patients aged 85 years or more at
      stroke onset and to investigate very old age as an independent predictor of short
      and long-term outcome. METHODS: In the community-based Copenhagen Stroke Study
      we recorded admission clinical characteristics in 1197 consecutive stroke
      patients. Patients were stratified according to age groups on admission. Follow
      up was performed at a mean of 7 years after stroke onset. By way of multiple
      logistic regression and survival analyses very old age was independently related
      to short- and long-term mortality and nursing home placement independent of other
      clinical characteristics. RESULTS: 16% of patients were 85 years or older at the
      time of stroke onset. More of the very old were women (75% versus 50%, P<0.0001),
      living alone (84% versus 54%, P<0.0001), had atrial fibrillation (37% versus 15%,
      P<0.0001), had pre-existing disability (29% versus 22%, P = 0.04), and had more
      severe strokes (Scandinavian Stroke Scale score 31 versus 37 points, P = 0.004).
      Fewer very old had hypertension (25% versus 34%, P = 0.02) and diabetes (14%
      versus 22%, P = 0.01). In adjusted multiple regression models, very old age
      predicted short-term mortality (OR 2.5; 95% CI 1.5-4.2), and discharge to nursing
      home or in-hospital mortality (OR 2.7; 95% CI 1.7-4.4). Five years after stroke
      very old age predicted mortality or nursing home placement (OR 3.9; 95% CI 2.1
      7.3), and long-term mortality (HR 2.0; 95% CI 1.6-2.5). However, other factors
      such as onset stroke severity, pre-existing disability and atrial fibrillation
      were also significant independent predictors of prognosis after stroke.
      CONCLUSIONS: In this study very old age per se was a strong predictor of outcome
      and mortality after stroke. Apart from very old age, factors such as prestroke
      medical and functional status, and onset stroke severity should be taken into
      consideration when planning treatment and rehabilitation after stroke.

PMID- 14960431
TI  - Effects of ageing on gastrointestinal motor function.
AB  - BACKGROUND: Existing data on the effect of ageing on gastrointestinal motility
      are few. In this study, we assessed the propulsive effect of all main segments of
      the gastrointestinal tract in a group of healthy older people. METHODS: 16
      healthy volunteers (eight women, eight men) of mean age 81 years (range 74-85
      years) participated in the study. Gastric emptying and small intestinal and
      colonic transit rates were determined by gamma camera technique. The technique
      was also used to measure the postprandial frequency of antral contractions.
      Furthermore, we assessed the effects of gender, body mass index and smoking on
      the motility variables. The results were compared with data from 16 healthy
      individuals (eight women, eight men) of mean age 24 years (range 20-30 years).
      RESULTS: Advanced age did not influence gastric emptying or small intestinal
      transit rate. Older individuals had a slower colonic transit than young
      individuals (P = 0.0008). No difference was found in postprandial frequency of
      antral contractions between older and young subjects. None of the motility
      variables was affected by gender or body mass index. Smokers had a faster colonic
      transit than non-smokers (P = 0.0022). CONCLUSION: Normal ageing seems to reduce
      the propulsive capacity of the colon, whereas gastric and small intestinal
      motility is not affected.

PMID- 14960432
TI  - Determinants of sleep quality in the healthy aged: the role of physical,
      psychological, circadian and naturalistic light variables.
AB  - Ageing is associated with a decrease in the quality of night-time sleep with 30%
      of aged persons experiencing chronic insomnia. Treatment of insomnia typically
      involves the use of hypnotic medications and these have been associated with a
      range of negative outcomes in this population cohort. The development of age
      related insomnia has been linked, in part, to changes in the strength of the
      circadian regulation of sleep, these changes typically leading to increased
      fragmentation of the sleep-wake cycle. Management of insomnia may therefore be
      linked to strengthening of these regulatory control mechanisms. Previous research
      has indicated that both daily activity levels and ambient light exposure may act
      as zeitgebers to consolidate sleep-wakefulness cycles. The current study utilised
      a naturalistic design to explore the relationship between light, activity and
      night-time sleep quality amongst a sample of 33 healthy aged subjects. Findings
      demonstrated a significant positive relationship between activity and sleep
      quality. Ambient light was also shown to have a significant impact on night-time
      sleep though the study identified a critical exposure threshold of 3000 lux.
      Factor analysis demonstrated the independent contribution of these two variables
      to subsequent sleep quality. The findings of the current study identify the
      potential for the development of non-pharmacological treatment strategies for
      insomnia in aged people.

PMID- 14960433
TI  - Dignity in older age: what do older people in the United Kingdom think?
AB  - BACKGROUND: Dignity is a complex concept and there is little empirical research
      to show how older people view dignity. This study, using qualitative methods,
      explored the concept of dignity from the older person's perspective. METHODS: 15
      focus groups and two individual interviews were conducted in 12 different
      settings, with a total of 72 participants. Participants were purposively sampled
      to ensure a mix of socio-economic status, ethnicity, gender, age (65+) and level
      of fitness. Focus groups were audio-taped and transcribed. The method of constant
      comparison was used to analyse the data. RESULTS: There was strong evidence to
      suggest that dignity was salient to the concerns of older people. Dignity was
      seen as a multi-faceted concept: (i). dignity of identity (self-respect/esteem,
      integrity, trust); (ii). human rights (equality, choice); and (iii). autonomy
      (independence, control). Examples of dignity being jeopardised rather than being
      enhanced were given. A loss of self-esteem arose from being patronised, excluded
      from decision-making, and being treated as an 'object'. Lack of integrity in
      society meant that there was an inability to trust others and an increased
      vulnerability. Equality was an important issue but many felt that government
      policies did not support their rights. CONCLUSIONS: This work identifies the
      different ways dignity is conceptualised by older people. The evidence showed
      that person centred care for older people needs to be specifically related to
      communication, privacy, personal identity and feelings of vulnerability. It
      provides evidence for policy makers and professionals to tailor policies and
      practices to the needs of the older person.

PMID- 14960434
TI  - Patterns and determinants of alcohol consumption in people aged 75 years and
      older: results from the MRC trial of assessment and management of older people in
      the community.
AB  - BACKGROUND: Very little work on alcohol consumption patterns in older people has
      been undertaken. As a result, knowledge about the prevalence and characteristics
      of regular drinkers and heavy drinkers in this age group remains limited.
      OBJECTIVE: To determine the socio-economic and health characteristics associated
      with different levels of alcohol intake in older people. DESIGN: Detailed
      screening of patients in one arm of a cluster randomised trial. SETTING: 53 UK
      general practices drawn from the Medical Research Council General Practice
      Research Framework. SUBJECTS: All patients aged 75 and over on the GP lists
      (excluding those in nursing homes or other long stay care) were invited to
      participate in the study. Of the 15358 people who received a detailed assessment
      in the 'universal' arm, 14962 (97%) of these answered questions on alcohol
      consumption. Of these, 62% were female and the median age was 80.3 years.
      METHODS: Associations between reported alcohol intake and various socio-economic
      and health variables were investigated, first in univariate analyses and then
      controlling for other variables in logistic regression models. RESULTS: 5% of men
      and 2.5% of women exceeded the Royal College of Physicians, Psychiatrists and
      General Practitioners' recommended drinking limits of 21 and 14 units a week
      respectively; 17% of subjects had never had a drink. Women and the very elderly
      were less likely to be drinkers. Those that drank were more likely to be people
      who still had a fairly active and sociable lifestyle, and with a better self
      perceived health status compared with non-drinkers. Moderate drinkers were also
      less likely to be severely cognitively impaired compared with non-drinkers:
      adjusted odds ratio 0.69 (95% CI 0.57, 0.85); but more likely to report symptoms
      of anxiety: 1.31 (1.07, 1.61). CONCLUSIONS: Our results suggest that moderate
      alcohol consumption is associated with relative financial security and good
      health with the exception of higher levels of anxiety amongst drinkers.

PMID- 14960435
TI  - The effectiveness of implementing a care pathway for femoral neck fracture in
      older people: a prospective controlled before and after study.
AB  - OBJECTIVES: To investigate whether a care pathway for older hip fracture patients
      can reduce length of stay while maintaining the quality of clinical care. DESIGN:
      Prospective study of patients admitted 12 months before and after implementation
      of a care pathway for the management of femoral neck fracture. Audit data for
      corresponding time periods from nearby orthopaedic units was used to control for
      secular trends. SETTING: Teaching hospital. SUBJECTS: Patients aged 65 years and
      over with a femoral neck fracture. EXCLUSION CRITERIA: multiple fractures,
      fractures due to malignancy, re-fracture, total hip replacement, previously
      entered into the study, operation performed elsewhere. Three-hundred and ninety
      five (99%) and 369 (97%) case records were available for full analysis. MAIN
      OUTCOME MEASURES: primary outcome: length of stay on the orthopaedic unit.
      SECONDARY OUTCOMES: ambulation at discharge, discharge destination, in-hospital
      complications, 30 day mortality, readmission within 30 days of discharge, post
      operative days the patient first sat out of bed and walked. RESULTS: Mean length
      of stay increased by 6.5 days (95% confidence interval 3.5-9.5 days, P < 0.0005)
      in the second period with a significant improvement in ambulation on discharge
      (odds ratio 1.6, 95% confidence interval 1.0-2.6, P = 0.033) and a trend towards
      reduction in admission to long term care (odds ratio 0.6, 95% confidence interval
      0.3-1.0, P = 0.058). CONCLUSIONS: This care pathway was associated with longer
      hospital stay and improved clinical outcomes. Care pathways for hip fracture
      patients can be a useful tool for raising care standards but may require
      additional resources.

PMID- 14960436
TI  - Inhaler technique in older people in the community.
AB  - BACKGROUND: Good inhaler technique and medication concordance is important for
      symptom and disease control in chronic airways disease. OBJECTIVES: Establish the
      prevalence of inhaler use; the main inhaler devices used by older people at home;
      their ability to use the inhalers they have been prescribed; and the relationship
      between perceived ease of use and actual performance. DESIGN: Cross-sectional
      population based study. SUBJECTS: Subjects aged 70 years and over living at home.
      METHODS: 500 subjects were randomly selected from 5002 subjects aged 70 years and
      over living at home. Inhalers used over the previous 24 hours were identified by
      a nurse on home visit. Those with cognitive impairment were excluded. Inhaler
      system was assessed and graded by a doctor as acceptable (perfect or minor
      errors) or unacceptable (major errors), using previously published criteria.
      Perceived ease of use of the device was rated as easy, moderate or difficult.
      RESULTS: 423 subjects participated in the study. The population prevalence of
      inhaler use was 15.8% (12.0, 19.7). Of the 91 inhaler devices used, 39 (42.8%)
      were metered dose inhalers, 34 (37.4%) were metered dose inhalers with large
      volume spacers, and 18 (19.8%) were breath-actuated devices. Thirty-two subjects
      (82.1%) using metered dose inhalers had an acceptable technique compared with 33
      (97.1%) of those using metered dose inhalers with large volume spacers and 13
      (72.2%) of those using breath-actuated devices (P < 0.05). Up to three quarters
      of inhalers were considered easy to use but 12% of subjects who rated their
      inhaler device as being easy to use made major errors. CONCLUSION: Metered dose
      inhaler was the most frequently prescribed inhaler and was used correctly by most
      subjects especially in combination with large volume spacers. Major errors were
      more common with breath-actuated devices. Inhaler technique should be checked as
      patients' perception of their inhaler skills correlates poorly with actual
      performance.

PMID- 14960437
TI  - Doctors' and nurses' observations on the Geriatric Depression Rating Scale.
AB  - BACKGROUND: Screening older patients routinely for depression using the Geriatric
      Depression Scale is recommended, but there is little evidence that this practice
      is widespread. This study explored doctors' and nurses' attitudes towards the
      Geriatric Depression Scale in order to identify possibilities for improving
      practice. DESIGN: structured interviews. SETTING: Acute Care of the Elderly wards
      in the Royal Liverpool University Hospital. PARTICIPANTS: 20 junior doctors and
      25 nurses. RESULTS: Only 10% of respondents would consider using the Geriatric
      Depression Scale for routine screening. Objections were to process as well as
      content. The Geriatric Depression Scale was felt to be 'too depressing' for
      routine use and a barrier to rapport with the patient. In addition to screening
      for possible depression, doctors and nurses expressed different requirements from
      a depression scale. Doctors wanted a formal method of rating and documenting
      symptoms. Nurses required a therapeutic structure within which they could help
      patients to explore feelings. Nurses also wanted the option of offering
      counselling for their patients but felt they needed training. CONCLUSIONS: Lack
      of enthusiasm for the Geriatric Depression Scale reduces its usefulness as a
      screening tool. A screening method that is more acceptable to nurses and doctors
      might improve depression screening practice.

PMID- 14960438
TI  - Dementia and hypertension in African/Caribbean elders.

PMID- 14960439
TI  - The impact of self-reported cumulative comorbidity on stroke recovery.

PMID- 14960440
TI  - Warfarin-associated thoracic aortic dissection in an elderly woman.
AB  - BACKGROUND: The risk/benefit ratio of warfarin therapy changes in the over 75s,
      when haemorrhagic side-effects become more common. These may not always be
      reported in the literature. CASE REPORT: A woman of 80 years, on long-term
      warfarin therapy presented with an acute dissecting thoracic aortic aneurysm; on
      investigation the only precipitating factor found was an international normalised
      ratio of 4.8. This patient, who also had an abdominal aortic aneurysm, survived,
      on discontinuation of her anticoagulant therapy. CONCLUSIONS: We describe a
      previously unreported complication of warfarin therapy in a patient over 75 years
      of age, to add to the cautions in prescribing this drug in patients of this age
      group.

PMID- 14960441
TI  - Continuous machinery murmur in an octogenarian.
AB  - BACKGROUND: Sinus of valsalva aneurysm is a rare congenital anomaly and usually
      presents in adolescence to early adulthood. Manifestations are varied, ranging
      from asymptomatic murmur to sudden death. CASE REPORT: An elderly male presented
      with chest pain and machinery murmur, which was confirmed as ruptured sinus of
      valsalva aneurysm on echocardiogram. Emergency surgical repair led to a
      successful outcome. DISCUSSION: Review of the literature revealed that this
      patient is the oldest reported case. Urgent echocardiography and surgical advice
      are essential. This condition is potentially treatable even in the older age
      group and the prognosis is good after surgical repair.

PMID- 14960442
TI  - Physical or psychological change? Which is the most important rehabilitation
      outcome for older people who fall?

PMID- 14960443
TI  - Awareness of over-the-counter drug use by elderly patients. A hospital-based
      questionnaire survey.

PMID- 14960444
TI  - Higher level gait disorders.

PMID- 14960445
TI  - ECF impairment is common.

PMID- 14960446
TI  - Amiodarone and cirrhosis.

PMID- 14960450
TI  - Ageism in access to critical care.

PMID- 14960451
TI  - Wealth and health of ageing.

PMID- 14960452
TI  - Re: Guidelines for the diagnosis and management of PMR/GCA.

PMID- 14960455
TI  - Pseudo-periodic partitions of biological sequences.
AB  - MOTIVATION: Algorithm development for finding typical patterns in sequences,
      especially multiple pseudo-repeats (pseudo-periodic regions), is at the core of
      many problems arising in biological sequence and structure analysis. In fact, one
      of the most significant features of biological sequences is their high quasi
      repetitiveness. Variation in the quasi-repetitiveness of genomic and proteomic
      texts demonstrates the presence and density of different biologically important
      information. It is very important to develop sensitive automatic computational
      methods for the identification of pseudo-periodic regions of sequences through
      which we can infer, describe and understand biological properties, and seek
      precise molecular details of biological structures, dynamics, interactions and
      evolution. RESULTS: We develop a novel, powerful computational tool for
      partitioning a sequence to pseudo-periodic regions. The pseudo-periodic partition
      is defined as a partition, which intuitively has the minimal bias to some perfect
      periodic partition of the sequence based on the evolutionary distance. We devise
      a quadratic time and space algorithm for detecting a pseudo-periodic partition
      for a given sequence, which actually corresponds to the shortest path in the main
      diagonal of the directed (acyclic) weighted graph constructed by the Smith
      Waterman self-alignment of the sequence. We use several typical examples to
      demonstrate the utilization of our algorithm and software system in detecting
      functional or structural domains and regions of proteins. A big advantage of our
      software program is that there is a parameter, the granularity factor, associated
      with it and we can freely choose a biological sequence family as a training set
      to determine the best parameter. In general, we choose all repeats (including
      many pseudo-repeats) in the SWISS-PROT amino acid sequence database as a typical
      training set. We show that the granularity factor is 0.52 and the average
      agreement accuracy of pseudo-periodic partitions, detected by our software for
      all pseudo-repeats in the SWISS-PROT database, is as high as 97.6%.

PMID- 14960456
TI  - affy--analysis of Affymetrix GeneChip data at the probe level.
AB  - MOTIVATION: The processing of the Affymetrix GeneChip data has been a recent
      focus for data analysts. Alternatives to the original procedure have been
      proposed and some of these new methods are widely used. RESULTS: The affy package
      is an R package of functions and classes for the analysis of oligonucleotide
      arrays manufactured by Affymetrix. The package is currently in its second
      release, affy provides the user with extreme flexibility when carrying out an
      analysis and make it possible to access and manipulate probe intensity data. In
      this paper, we present the main classes and functions in the package and
      demonstrate how they can be used to process probe-level data. We also demonstrate
      the importance of probe-level analysis when using the Affymetrix GeneChip
      platform.

PMID- 14960457
TI  - Hybrid simulation of cellular behavior.
AB  - MOTIVATION: To be valuable to biological or biomedical research, in silico
      methods must be scaled to complex pathways and large numbers of interacting
      molecular species. The correct method for performing such simulations, discrete
      event simulation by Monte Carlo generation, is computationally costly for large
      complex systems. Approximation of molecular behavior by continuous models fails
      to capture stochastic behavior that is essential to many biological phenomena.
      RESULTS: We present a novel approach to building hybrid simulations in which some
      processes are simulated discretely, while other processes are handled in a
      continuous simulation by differential equations. This approach preserves the
      stochastic behavior of cellular pathways, yet enables scaling to large
      populations of molecules. We present an algorithm for synchronizing data in a
      hybrid simulation and discuss the trade-offs in such simulation. We have
      implemented the hybrid simulation algorithm and have validated it by simulating
      the statistical behavior of the well-known lambda phage switch. Hybrid simulation
      provides a new method for exploring the sources and nature of stochastic behavior
      in cells.

PMID- 14960458
TI  - A benchmark for Affymetrix GeneChip expression measures.
AB  - MOTIVATION: The defining feature of oligonucleotide expression arrays is the use
      of several probes to assay each targeted transcript. This is a bonanza for the
      statistical geneticist, who can create probeset summaries with specific
      characteristics. There are now several methods available for summarizing probe
      level data from the popular Affymetrix GeneChips, but it is difficult to identify
      the best method for a given inquiry. RESULTS: We have developed a graphical tool
      to evaluate summaries of Affymetrix probe level data. Plots and summary
      statistics offer a picture of how an expression measure performs in several
      important areas. This picture facilitates the comparison of competing expression
      measures and the selection of methods suitable for a specific investigation. The
      key is a benchmark data set consisting of a dilution study and a spike-in study.
      Because the truth is known for these data, we can identify statistical features
      of the data for which the expected outcome is known in advance. Those features
      highlighted in our suite of graphs are justified by questions of biological
      interest and motivated by the presence of appropriate data.

PMID- 14960459
TI  - Model-based methods for identifying periodically expressed genes based on time
      course microarray gene expression data.
AB  - MOTIVATION: The expressions of many genes associated with certain periodic
      biological and cell cycle processes such as circadian rhythm regulation are known
      to be rhythmic. Identification of the genes whose time course expressions are
      synchronized to certain periodic biological process may help to elucidate the
      molecular basis of many diseases, and these gene products may in turn represent
      drug targets relevant to those diseases. RESULTS: We propose in this paper a
      statistical framework based on a shape-invariant model together with a false
      discovery rate (FDR) procedure for identifying periodically expressed genes based
      on microarray time-course gene expression data and a set of known periodically
      expressed guide genes. We applied the proposed methods to the alpha-factor, cdc15
      and cdc28 synchronized yeast cell cycle data sets and identified a total of 1010
      cell-cycle-regulated genes at a FDR of 0.5% in at least one of the three data
      sets analyzed, including 89 (86%) of 104 known periodic transcripts. We also
      identified 344 and 201 circadian rhythmic genes in vivo in mouse heart and liver
      tissues with FDR of 10 and 2.5%, respectively. Our results also indicate that the
      shape-invariant model fits the data well and provides estimate of the common
      shape function and the relative phases for these periodically regulated genes.

PMID- 14960460
TI  - Functional topology in a network of protein interactions.
AB  - MOTIVATION: The building blocks of biological networks are individual protein
      protein interactions (PPIs). The cumulative PPI data set in Saccharomyces
      cerevisiae now exceeds 78 000. Studying the network of these interactions will
      provide valuable insight into the inner workings of cells. RESULTS: We performed
      a systematic graph theory-based analysis of this PPI network to construct
      computational models for describing and predicting the properties of lethal
      mutations and proteins participating in genetic interactions, functional groups,
      protein complexes and signaling pathways. Our analysis suggests that lethal
      mutations are not only highly connected within the network, but they also satisfy
      an additional property: their removal causes a disruption in network structure.
      We also provide evidence for the existence of alternate paths that bypass viable
      proteins in PPI networks, while such paths do not exist for lethal mutations. In
      addition, we show that distinct functional classes of proteins have differing
      network properties. We also demonstrate a way to extract and iteratively predict
      protein complexes and signaling pathways. We evaluate the power of predictions by
      comparing them with a random model, and assess accuracy of predictions by
      analyzing their overlap with MIPS database. CONCLUSIONS: Our models provide a
      means for understanding the complex wiring underlying cellular function, and
      enable us to predict essentiality, genetic interaction, function, protein
      complexes and cellular pathways. This analysis uncovers structure-function
      relationships observable in a large PPI network.

PMID- 14960461
TI  - An ontology for collaborative construction and analysis of cellular pathways.
AB  - MOTIVATION: As the scientific curiosity in genome studies shifts toward
      identification of functions of the genomes in large scale, data produced about
      cellular processes at molecular level has been accumulating with an accelerating
      rate. In this regard, it is essential to be able to store, integrate, access and
      analyze this data effectively with the help of software tools. Clearly this
      requires a strong ontology that is intuitive, comprehensive and uncomplicated.
      RESULTS: We define an ontology for an intuitive, comprehensive and uncomplicated
      representation of cellular events. The ontology presented here enables
      integration of fragmented or incomplete pathway information via collaboration,
      and supports manipulation of the stored data. In addition, it facilitates
      concurrent modifications to the data while maintaining its validity and
      consistency. Furthermore, novel structures for representation of multiple levels
      of abstraction for pathways and homologies is provided. Lastly, our ontology
      supports efficient querying of large amounts of data. We have also developed a
      software tool named pathway analysis tool for integration and knowledge
      acquisition (PATIKA) providing an integrated, multi-user environment for
      visualizing and manipulating network of cellular events. PATIKA implements the
      basics of our ontology.

PMID- 14960462
TI  - Advanced significance analysis of microarray data based on weighted resampling: a
      comparative study and application to gene deletions in Mycobacterium bovis.
AB  - MOTIVATION: When analyzing microarray data, non-biological variation introduces
      uncertainty in the analysis and interpretation. In this paper we focus on the
      validation of significant differences in gene expression levels, or normalized
      channel intensity levels with respect to different experimental conditions and
      with replicated measurements. A myriad of methods have been proposed to study
      differences in gene expression levels and to assign significance values as a
      measure of confidence. In this paper we compare several methods, including SAM,
      regularized t-test, mixture modeling, Wilk's lambda score and variance
      stabilization. From this comparison we developed a weighted resampling approach
      and applied it to gene deletions in Mycobacterium bovis. RESULTS: We discuss the
      assumptions, model structure, computational complexity and applicability to
      microarray data. The results of our study justified the theoretical basis of the
      weighted resampling approach, which clearly outperforms the others.

PMID- 14960463
TI  - Non-parametric, hypothesis-based analysis of microarrays for comparison of
      several phenotypes.
AB  - MOTIVATION: We present a statistical framework for the analysis of high
      dimensional microarray data, where the goal is to compare intensities among
      several groups based on as few as a single sample from each group. In this
      setting, it is of interest to compare gene expression among several phenotypes to
      define candidate genes that simultaneously characterize several criteria,
      simultaneously, among the comparison groups. We motivate the approach by a
      comparative microarray experiment in which clones of a cell were singly exposed
      to several distinct but related conditions. The experiment was conducted to
      elucidate genes involved in pathways leading to T cell clonal anergy. RESULTS: By
      integrating inference principles within a bioinformatics setting, we introduce a
      two-stage approach to select candidate genes that characterize several criteria.
      The method is unified in its non-parametric approach to inference and
      description. For inference, we construct a testable hypothesis based on the
      criteria of interest in a high-dimensional space, while preserving the dependence
      among genes. Upon rejecting the null, we estimate the cardinality of a set of
      individual candidate genes (or gene pairs) that depict the events of interest.
      With this estimate, we then select individual genes (or gene pairs) based upon a
      two-dimensional ranking that examines relations within and between genes, among
      comparison groups, using singular value decomposition in combination with inner
      product concepts.

PMID- 14960464
TI  - Is cross-validation valid for small-sample microarray classification?
AB  - MOTIVATION: Microarray classification typically possesses two striking
      attributes: (1) classifier design and error estimation are based on remarkably
      small samples and (2) cross-validation error estimation is employed in the
      majority of the papers. Thus, it is necessary to have a quantifiable
      understanding of the behavior of cross-validation in the context of very small
      samples. RESULTS: An extensive simulation study has been performed comparing
      cross-validation, resubstitution and bootstrap estimation for three popular
      classification rules-linear discriminant analysis, 3-nearest-neighbor and
      decision trees (CART)-using both synthetic and real breast-cancer patient data.
      Comparison is via the distribution of differences between the estimated and true
      errors. Various statistics for the deviation distribution have been computed:
      mean (for estimator bias), variance (for estimator precision), root-mean square
      error (for composition of bias and variance) and quartile ranges, including
      outlier behavior. In general, while cross-validation error estimation is much
      less biased than resubstitution, it displays excessive variance, which makes
      individual estimates unreliable for small samples. Bootstrap methods provide
      improved performance relative to variance, but at a high computational cost and
      often with increased bias (albeit, much less than with resubstitution).

PMID- 14960465
TI  - A graph-theoretic modeling on GO space for biological interpretation of gene
      clusters.
AB  - MOTIVATION: With the advent of DNA microarray technologies, the parallel
      quantification of genome-wide transcriptions has been a great opportunity to
      systematically understand the complicated biological phenomena. Amidst the
      enthusiastic investigations into the intricate gene expression data, clustering
      methods have been the useful tools to uncover the meaningful patterns hidden in
      those data. The mathematical techniques, however, entirely based on the numerical
      expression data, do not show biologically relevant information on the clustering
      results. RESULTS: We present a novel methodology for biological interpretation of
      gene clusters. Our graph theoretic algorithm extracts common biological
      attributes of the genes within a cluster or a group of interest through the
      modified structure of gene ontology (GO) called GO tree. After genes are
      annotated with GO terms, the hierarchical nature of GO terms is used to find the
      representative biological meanings of the gene clusters. In addition, the
      biological significance of gene clusters can be assessed quantitatively by
      defining a distance function on the GO tree. Our approach has a complementary
      meaning to many statistical clustering techniques; we can see clustering problems
      from a different viewpoint by use of biological ontology. We applied this
      algorithm to the well-known data set and successfully obtained the biological
      features of the gene clusters with the quantitative biological assessment of
      clustering quality through GO Biological Process.

PMID- 14960466
TI  - Knowledge discovery by automated identification and ranking of implicit
      relationships.
AB  - MOTIVATION: New relationships are often implicit from existing information, but
      the amount and growth of published literature limits the scope of analysis an
      individual can accomplish. Our goal was to develop and test a computational
      method to identify relationships within scientific reports, such that large sets
      of relationships between unrelated items could be sought out and statistically
      ranked for their potential relevance as a set. RESULTS: We first construct a
      network of tentative relationships between 'objects' of biomedical research
      interest (e.g. genes, diseases, phenotypes, chemicals) by identifying their co
      occurrences within all electronically available MEDLINE records. Relationships
      shared by two unrelated objects are then ranked against a random network model to
      estimate the statistical significance of any given grouping. When compared
      against known relationships, we find that this ranking correlates with both the
      probability and frequency of object co-occurrence, demonstrating the method is
      well suited to discover novel relationships based upon existing shared
      relationships. To test this, we identified compounds whose shared relationships
      predicted they might affect the development and/or progression of cardiac
      hypertrophy. When laboratory tests were performed in a rodent model,
      chlorpromazine was found to reduce the progression of cardiac hypertrophy.

PMID- 14960467
TI  - Parallel Metropolis coupled Markov chain Monte Carlo for Bayesian phylogenetic
      inference.
AB  - MOTIVATION: Bayesian estimation of phylogeny is based on the posterior
      probability distribution of trees. Currently, the only numerical method that can
      effectively approximate posterior probabilities of trees is Markov chain Monte
      Carlo (MCMC). Standard implementations of MCMC can be prone to entrapment in
      local optima. Metropolis coupled MCMC [(MC)(3)], a variant of MCMC, allows
      multiple peaks in the landscape of trees to be more readily explored, but at the
      cost of increased execution time. RESULTS: This paper presents a parallel
      algorithm for (MC)(3). The proposed parallel algorithm retains the ability to
      explore multiple peaks in the posterior distribution of trees while maintaining a
      fast execution time. The algorithm has been implemented using two popular
      parallel programming models: message passing and shared memory. Performance
      results indicate nearly linear speed improvement in both programming models for
      small and large data sets.

PMID- 14960468
TI  - LDDist: a Perl module for calculating LogDet pair-wise distances for protein and
      nucleotide sequences.
AB  - LDDist is a Perl module implemented in C++ that allows the user to calculate
      LogDet pair-wise genetic distances for amino acid as well as nucleotide sequence
      data. It can handle site-to-site rate variation by treating a proportion of the
      sites as invariant and/or by assigning sites to different, presumably homogenous,
      rate categories. The rate-class assignments and invariant proportion can be set
      explicitly, or estimated by the program; the latter using either of two different
      capture-recapture methods. The assignment to rate categories in lieu of a
      phylogeny can be done using Shannon-Wiener index as a crude token for relative
      rate.

PMID- 14960469
TI  - Predicting protein secondary structure by cascade-correlation neural networks.
AB  - The back-propagation neural network algorithm is a commonly used method for
      predicting the secondary structure of proteins. Whilst popular, this method can
      be slow to learn and here we compare it with an alternative: the cascade
      correlation architecture. Using a constructive algorithm, cascade-correlation
      achieves predictive accuracies comparable to those obtained by back-propagation,
      in shorter time.

PMID- 14960470
TI  - SVM based method for predicting HLA-DRB1*0401 binding peptides in an antigen
      sequence.
AB  - Prediction of peptides binding with MHC class II allele HLA-DRB1(*)0401 can
      effectively reduce the number of experiments required for identifying helper T
      cell epitopes. This paper describes support vector machine (SVM) based method
      developed for identifying HLA-DRB1(*)0401 binding peptides in an antigenic
      sequence. SVM was trained and tested on large and clean data set consisting of
      567 binders and equal number of non-binders. The accuracy of the method was 86%
      when evaluated through 5-fold cross-validation technique.

PMID- 14960471
TI  - PIVOT: protein interacions visualizatiOn tool.
AB  - Protein Interaction VisualizatiOn Tool (PIVOT) is a visualization tool for
      protein-protein interactions. It allows the user to create personal data sets of
      interactions by combining information from private and public data sources. The
      user can gradually access the interactions' data using a clear interactive map
      that is focused on the researcher's protein of interest, and is reshaped and
      expanded in response to his/her queries. It also offers several visual
      enhancements and intelligent queries that help the user efficiently study it.
      PIVOT allows the user to search the interactions data set for paths connecting
      proteins that are expected to co-operate. The user can also employ PIVOT to
      predict unknown interactions among proteins, based on interactions among their
      homologous proteins in other species.

PMID- 14960472
TI  - The Jalview Java alignment editor.
AB  - Multiple sequence alignment remains a crucial method for understanding the
      function of groups of related nucleic acid and protein sequences. However, it is
      known that automatic multiple sequence alignments can often be improved by manual
      editing. Therefore, tools are needed to view and edit multiple sequence
      alignments. Due to growth in the sequence databases, multiple sequence alignments
      can often be large and difficult to view efficiently. The Jalview Java alignment
      editor is presented here, which enables fast viewing and editing of large
      multiple sequence alignments.

PMID- 14960473
TI  - SEPON, a Selection and Evaluation Pipeline for OligoNucleotides based on ESTs
      with a non-target Tm algorithm for reducing cross-hybridization in microarray
      gene expression experiments.
AB  - SEPON, Selection and Evaluation Pipeline for OligoNucleotide generates n-mer
      oligonucleotide sequences from expressed sequence tags of non-annotated genomes
      for microarray gene-expression profiling. A non-target melting temperature (T(m))
      algorithm will reduce cross-hybridization by estimating T(m) of oligonucleotide
      hybridization to non-specific targets (non-target T(m)) and discard
      oligonucleotides with non-target T(m) estimate above user-defined threshold.
      SEPON allows user-defined filtering, predicts exon location, assigns penalty
      based on 3' distance, GC content, secondary structure T(m) and non-target T(m)
      and ranks oligonucleotides for optimal selection.

PMID- 14960474
TI  - Gene specific siRNA selector.
AB  - Small interfering RNA (siRNA) is used in functional genomics applications to
      decrease the expression of a target gene, which may yield a biological effect
      that suggests a function for the target gene. The siRNA design tool scans a
      target gene for candidate siRNA sequences that satisfy user-adjustable rules.
      Selected candidates are then screened to identify those siRNA sequences that are
      specific to the gene of interest.

PMID- 14960475
TI  - VisCoSe: visualization and comparison of consensus sequences.
AB  - We introduce visualization and comparison of consensus sequences (VisCoSe) as a
      WWW service and a stand-alone command line Perl script for visualizing and
      comparing consensus sequences of protein and nucleotide sequences. VisCoSe is the
      only interface available that simultaneously calculates consensus sequences of
      multiple data sets and automatically compares these consensus sequences.
      Furthermore, VisCoSe allows visualization of chemical properties of amino acids.

PMID- 14960476
TI  - HIVbase: a PC/Windows-based software offering storage and querying power for
      locally held HIV-1 genetic, experimental and clinical data.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) research involves ongoing,
      repetitious sequencing of the HIV genome and the massive accumulation of
      associated investigational data. As a result, the storage of annotated DNA and/or
      protein sequences, as well as information retrieval, have become increasingly
      difficult tasks, with scientists extracting less information from their collected
      data than they should. OBJECTIVES: Our objective was to design and develop a
      software package to aid researchers in the storage, analysis and exploration of
      their HIV-associated data. RESULTS: HIVbase contains familiar, easy-to-use
      interfaces and functionality for integrating many types of disparate data. The
      software contains tools that allow for the mass import of raw genetic data,
      eliminate repetitious sequence translations, have the ability to identify
      automatically and store HIV regions of interest from nucleic acid or protein
      sequences, allow for the export of data in commonly used analysis-ready formats,
      and for unique querying approaches.

PMID- 14960477
TI  - Frequency Finder: a multi-source web application for collection of public allele
      frequencies of SNP markers.
AB  - Publicly available single nucleotide polymorphism (SNP) allele frequencies are an
      important resource for the selection of genetic markers that may be most useful
      for gene mapping and association studies. Data mining these allele frequencies
      through disparate public databases and Websites is time consuming and can result
      in inconsistent findings. We have developed a web-based software tool, Frequency
      Finder, to acquire SNP allele frequencies from multiple public data sources and
      return a summarized result to the user. Our software optimizes and automates the
      search of candidate markers, decreasing the amount of time it would take to
      extract pertinent data manually. We have included several methods to output the
      data, including on-screen and as a compressed text file. We show that Frequency
      Finder accurately retrieves available frequency data from the available sources.
      Using this tool, we detect significant differences between Asian, African and
      Caucasian populations in the allele frequency spectra of 246 097 SNPs. While
      limited to public databases that provide web-based access to allele frequencies,
      Frequency Finder provides a single, user-friendly interface for retrieving allele
      frequencies for large batches of SNPs from multiple data sources.

PMID- 14960478
TI  - Adenosine triphosphate concentration and beta-D-glucuronidase activity as
      indicators of sea bass semen quality.
AB  - The most common parameters used to evaluate sperm quality are motility rate and
      duration and fertilization ability. In this study, chemical and biochemical
      parameters of sea bass (Dicentrarchus labrax) sperm were investigated to find an
      alternative method for evaluating sperm fertilization ability before and after
      cryopreservation. The biochemical and chemical analyses were performed with fresh
      and frozen-thawed sperm and seminal plasma. To cryopreserve sperm, 250-microl
      straws were used. Fertilization ability was evaluated by inseminating eggs
      (obtained from hormonally stimulated females) with fresh and cryopreserved sperm.
      The results revealed a linear relationship (P < 0.05) between semen fertilization
      capacity and some seminal plasma (beta-D-glucuronidase activity, potassium
      concentration) and sperm (ATP concentration, aspartate aminotransferase activity)
      parameters. Variations in semen fertilization rate could be best described by two
      multiple regression models: one including the sperm parameters and another
      including the seminal plasma parameters. For practical application, the use of
      simple regression models is of value. Fertilization rate in both fresh and
      cryopreserved sperm was reliably predicted by determining the ATP concentration
      or the beta-D-glucuronidase activity or both.

PMID- 14960479
TI  - Testicular activity of Mos in the frog, Rana esculenta: a new role in
      spermatogonial proliferation.
AB  - Mos is a MAPK kinase kinase with an expression that is highly restricted to the
      gonads. Its function is mainly associated to the meiotic metaphase II arrest
      occurring during female gametogenesis, whereas to our knowledge, its role during
      spermatogenesis has not yet clarified. In the present paper, we report the
      isolation of c-mos cDNA and the identification of a 60-kDa Mos protein from the
      testis of the anuran amphibian, Rana esculenta. Both the transcript and the
      protein are always present at low levels in the testis during the frog annual
      sexual cycle, with single significant peaks of expression in March and May,
      respectively. Mos is mainly localized in the cytoplasm of primary and secondary
      spermatogonia (SPG). Therefore, we have used treatments with ethane-dimethane
      sulphonate (EDS), which blocks spermatogonial mitosis in frogs. Four days after a
      single EDS injection, Mos expression in SPG highly increases concomitantly with
      the temporary arrest of mitosis. From 8 to 28 days after the injection, the
      normal proliferative activity of SPG is restored, and Mos expression gradually
      decreases to control levels. These results strongly indicate that the c-mos proto
      oncogene exerts a new role associated to the regulation of spermatogonial
      proliferation.

PMID- 14960480
TI  - Analysis of cell-type-specific gene expression during mouse spermatogenesis.
AB  - In rodents, changes in gene expression during spermatogenesis can be monitored by
      sampling testis from each day during postnatal development. However, changes in
      gene expression at the tissue level can reflect changes in the concentration of
      an mRNA in a specific cell type, changes in volume of specific cells, or changes
      in the cell-type composition. This reflects the cellularity of the tissue. Here
      we have combined techniques that assess the expression profiles of genes at the
      whole-tissue level, differential display and DNA array, and, at the level of
      cellularity, in situ hybridization. Combining results from these techniques
      allows determination of the cell-type-specific gene-expression patterns of many
      genes during spermatogenesis. Differential display was used to determine
      expression profiles with high sensitivity and independent of prior knowledge of
      the sequence, whereas DNA arrays quickly assess the expression profiles of all
      the genes. This identified three groups of gene-expression profiles. The major
      group corresponds to genes that are upregulated in spermatocytes during either
      the mid- or late- pachytene phase of spermatogenesis (stages VII-XI). This
      pachytene cluster was gradually extinguished in the later spermatid stages but
      was followed by another cluster of genes expressed in spermatids. Finally, a
      group of genes was downregulated during spermatogenesis and probably expressed in
      nongerm cells. We believe that expression of most genes can be described by a
      combination of these cell-type-specific expression patterns.

PMID- 14960481
TI  - Involvement of histone H3 (Ser10) phosphorylation in chromosome condensation
      without Cdc2 kinase and mitogen-activated protein kinase activation in pig
      oocytes.
AB  - When oocytes resume meiosis, chromosomes start to condense and Cdc2 kinase
      becomes activated. However, recent findings show that the chromosome condensation
      does not always correlate with the Cdc2 kinase activity in pig oocytes. The
      objectives of this study were to examine 1) the correlation between chromosome
      condensation and histone H3 phosphorylation at serine 10 (Ser10) during the
      meiotic maturation of pig oocytes and 2) the effects of protein phosphatase 1/2A
      (PP1/ PP2A) inhibitors on the chromosome condensation and the involvement of Cdc2
      kinase, MAP kinase, and histone H3 kinase in this process. The phosphorylation of
      histone H3 (Ser10) was first detected in the clump of condensed chromosomes at
      the diakinesis stage and was maintained until metaphase II. The kinase assay
      showed that histone H3 kinase activity was low in oocytes at the germinal vesicle
      stage (GV) and increased at the diakinesis stage and that high activity was
      maintained until metaphase II. Treatment of GV-oocytes with okadaic acid (OA) or
      calyculin-A (CL-A), the PP1/PP2A inhibitors, induced rapid chromosome
      condensation with histone H3 (Ser10) phosphorylation after 2 h. Both histone H3
      kinase and MAP kinase were activated in the treated oocytes, although Cdc2 kinase
      was not activated. In the oocytes treated with CL-A and the MEK inhibitor U0126,
      neither Cdc2 kinase nor MAP kinase were activated and no oocytes underwent
      germinal vesicle breakdown (GVBD), although histone H3 kinase was still activated
      and the chromosomes condensed with histone H3 (Ser10) phosphorylation. These
      results suggest that the phosphorylation of histone H3 (Ser10) occurs in
      condensed chromosomes during maturation in pig oocytes. Furthermore, the
      chromosome condensation is correlated with histone H3 kinase activity but not
      with Cdc2 kinase and MAP kinase activities.

PMID- 14960482
TI  - Freeze-dried sperm fertilization leads to full-term development in rabbits.
AB  - To date, the laboratory mouse is the only mammal in which freeze-dried
      spermatozoa have been shown to support full-term development after microinjection
      into oocytes. Because spermatozoa in mice, unlike in most other mammals, do not
      contribute centrosomes to zygotes, it is still unknown whether freeze-dried
      spermatozoa in other mammals are fertile. Rabbit sperm was selected as a model
      because of its similarity to human sperm (considering the centrosome inheritance
      pattern). Freeze- drying induces rabbit spermatozoa to undergo dramatic changes,
      such as immobilization, membrane breaking, and tail fragmentation. Even when
      considered to be "dead" in the conventional sense, rabbit spermatozoa freeze
      dried and stored at ambient temperature for more than 2 yr still have capability
      comparable to that of fresh spermatozoa to support preimplantation development
      after injection into oocytes followed by activation. A rabbit kit derived from a
      freeze-dried spermatozoon was born after transferring 230 sperm-injected oocytes
      into eight recipients. The results suggest that freeze-drying could be applied to
      preserve the spermatozoa from most other species, including human. The present
      study also raises the question of whether rabbit sperm centrosomes survive freeze
      drying or are not essential for embryonic development.

PMID- 14960483
TI  - Exposure of mouse preimplantation embryos to 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) alters the methylation status of imprinted genes H19 and Igf2.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an extremely toxic, persistent
      environmental contaminant that disrupts normal development in laboratory animals.
      In our earlier study, we found that exposure of preimplantation embryos to TCDD
      markedly induced cytochrome P4501A1 mRNA at the blastocyst stage. In the present
      study, to determine whether exposure of preimplantation embryos to TCDD affects
      fetal growth, we exposed preimplantation embryos to TCDD from the 1-cell stage to
      the blastocyst stage and then transferred them to unexposed recipient mice. On
      Embryonic Day 14, the fetuses exposed to TCDD during the preimplantation stage
      weighed less than the fetuses in the unexposed control group. Real-time reverse
      transcription-polymerase chain reaction analysis revealed that exposure of
      preimplantation embryos to TCDD tended to decrease the expression levels of the
      imprinted genes H19 and Igf2 (insulin-like growth factor 2 gene). Use of
      bisulfite genomic sequencing demonstrated that the methylation level of the 430-
      base pair H19/Igf2 imprint control region was higher in TCDD- exposed embryos and
      fetuses than in the controls, and methyltransferase activity was also higher in
      the TCDD-exposed embryos than in the controls. To our knowledge, the present
      study is the first to provide evidence that TCDD exposure at the preimplantation
      stage alters the genomic DNA methylation status of imprinted genes, influences
      the expression level of imprinted genes, and affects fetal development.

PMID- 14960484
TI  - Effects of leptin on fetal plasma adrenocorticotropic hormone and cortisol
      concentrations and the timing of parturition in the sheep.
AB  - We investigated whether leptin can suppress the prepartum activation of the fetal
      hypothalamus-pituitary-adrenal (HPA) axis and delay the timing of parturition in
      the sheep. First, we investigated the effects of a 4-day intravascular infusion
      of recombinant ovine leptin (n = 7) or saline (n = 6) on fetal plasma
      adrenocorticotropic hormone (ACTH) and cortisol concentrations, starting from 136
      days gestation (i.e., at the onset of the prepartum activation of the fetal HPA
      axis. The effects of a continuous intrafetal infusion of leptin (n = 7) or saline
      (n = 5) from 144 days gestation on fetal plasma ACTH and cortisol concentrations
      and the timing of delivery were also determined in a separate study. There was an
      increase in fetal plasma ACTH (P < 0.01) and cortisol (P < 0.001) concentrations
      when saline was infused between 136-137 and 140-141 days gestation. Plasma ACTH
      and cortisol concentrations did not rise, however, when leptin was infused during
      this period of gestation. When leptin was infused after 144 days gestation, there
      was no effect of a 4- to 5-fold increase in circulating leptin on fetal ACTH
      concentrations. In contrast, leptin infusion from 144 days gestation suppressed
      (P < 0.05) fetal plasma cortisol concentrations by around 40% between 90 and 42 h
      before delivery. There was no difference, however, in the length of gestation
      between the saline- and leptin-infused groups (saline infused, 150.2 +/- 0.5
      days; leptin infused, 149.8 +/- 1.0 days). In saline-infused fetuses, there was a
      significant negative relationship between the plasma concentrations of cortisol
      (y) and leptin (x) between 138 and 146 days gestation (y = 81.4 - 7.7x, r = 0.38,
      P < 0.005). This study provides evidence for an endocrine negative feedback loop
      between leptin and the HPA axis in fetal life.

PMID- 14960485
TI  - Normoxic induction of the hypoxic-inducible factor-1 alpha by interleukin-1 beta
      involves the extracellular signal-regulated kinase 1/2 pathway in normal human
      cytotrophoblast cells.
AB  - During early pregnancy, an environment of relative low oxygen tension is
      essential for normal embryonic and placental vasculature. In low-oxygen
      conditions, the hypoxic-inducible factor-1 (HIF-1), composed of alpha and beta
      subunits, controls the expression of a number of genes such as vascular
      endothelial growth factor (VEGF), a key angiogenic factor. The recent studies in
      some tumor cells have found that the labile component, HIF-1 alpha, is not only
      activated by hypoxia but also by peptides such as interleukin-1 (IL-1) in
      normoxia. In this article, we demonstrated that exposure of normal human
      cytotrophoblast cells to IL-1 beta stimulated the expression of HIF-1 alpha
      protein. Meanwhile, IL-1 beta also induced the secretion of VEGF in normal human
      cytotrophoblast cells. Our data indicated that IL-1 beta induced extracellular
      signal-regulated kinase (ERK) 1/2 phosphorylation. Moreover, treatment of cells
      with PD98059, an inhibitor of ERK1/2 signaling, inhibited the stimulation of HIF
      1 alpha protein expression and VEGF secretion by IL-1 beta. These data indicate
      that, in normal human cytotrophoblast cells, IL-1 beta induces HIF- 1 alpha
      mediated VEGF secretion and that IL-1 beta-stimulated ERK1/2 activation may be
      involved in this process.

PMID- 14960486
TI  - Reorganization of microfilaments and microtubules by thermal stress in two-cell
      bovine embryos.
AB  - Two-cell bovine embryos become arrested in development when exposed to a
      physiologically relevant heat shock. One of the major ultrastructural
      modifications caused by heat shock is translocation of organelles toward the
      center of the blastomere. The objective of the present study was to determine if
      heat- shock-induced movement of organelles is a result of cytoskeletal
      rearrangement. Two-cell bovine embryos were cultured at 38.5 degrees C
      (homeothermic temperature of the cow), 41.0 degrees C (physiologically relevant
      heat shock), or 43.0 degrees C (severe heat shock) for 6 h in the presence of
      either vehicle, latrunculin B (a microfilament depolymerizer), rhizoxin (a
      microtubule depolymerizer), or paclitaxel (a microtubule stabilizer). Heat shock
      caused a rearrangement of actin-containing filaments as detected by staining with
      phalloidin. Moreover, latrunculin B reduced the heat-shock-induced movement of
      organelles at 41.0 degrees C but not at 43.0 degrees C. In contrast, movement of
      organelles caused by heat shock was inhibited by rhizoxin at both temperatures.
      Furthermore, rhizoxin, but not latrunculin B, reduced the swelling of
      mitochondria caused by heat shock. Paclitaxel, while causing major changes in
      ultrastructure, did not prevent the movement of organelles or mitochondrial
      swelling. It is concluded that heat shock disrupts microtubule and microfilaments
      in the two-cell bovine embryo and that these changes are responsible for movement
      of organelles away from the periphery. In addition, intact microtubules are a
      requirement for heat-shock-induced swelling of mitochondria. Differences in
      response to rhizoxin and paclitaxel are interpreted to mean that deformation of
      microtubules can occur through a mechanism independent of microtubule
      depolymerization.

PMID- 14960487
TI  - Studies on the effects of the N-terminal domain antibodies of calcitonin receptor
      like receptor and receptor activity-modifying protein 1 on calcitonin gene
      related peptide-induced vasorelaxation in rat uterine artery.
AB  - The vascular relaxation sensitivity to calcitonin gene-related peptide (CGRP) is
      enhanced during pregnancy, compared with nonpregnant human and rat uterine
      arteries. In the rat uterine artery, two types of CGRP receptors have been shown
      to coexist, CGRP-A receptor, which is a complex of calcitonin receptor-like
      receptor (CRLR), and receptor activity-modifying protein (RAMP(1)) and CGRP-B
      receptor, which is different from CRLR. In the present study, we hypothesized
      that: 1) CGRP-induced vasorelaxation in rat uterine artery is mediated through
      CGRP-A receptor and 2) N-terminal (Nt) domain of CRLR (Nt-CRLR) has a major
      contribution in ligand binding and mediating CGRP- induced relaxation effects in
      rat uterine artery. Polyclonal antibodies against Nt-domain of CRLR and RAMP(1)
      (Nt-RAMP(1)) were raised in rabbits and characterized for their specificity and
      were used to inhibit CGRP-induced vasorelaxation in rat uterine artery. For
      vascular relaxation studies, uterine arteries from Day 18 pregnant rats were
      isolated, and responsiveness of the vessels to CGRP was examined with a small
      vessel myograph. CGRP (10(-10) to 10(-7) M) produced a concentration-dependent
      relaxation of norepinephrine-induced contractions in Day 18 pregnant rat uterine
      arteries. These effects were significantly (P < 0.05) inhibited when uterine
      arteries were incubated with the antibody raised against Nt-CRLR (PD(2) = 6.75 +/
      0.20) and were totally abolished in presence of antibodies for both Nt-CRLR and
      Nt-RAMP(1) (PD(2) = 6.14 +/- 0.35). In contrast, a monoclonal antibody for CGRP-B
      receptor had no effect on CGRP-induced rat uterine artery relaxation. These
      studies suggest that CGRP effects in rat uterine artery are mediated through CGRP
      A receptor and that Nt-domain of CRLR may play a predominant role in CGRP binding
      and thus in causing CGRP-induced uterine artery relaxation.

PMID- 14960488
TI  - Effect of insulin-like growth factor-I during preantral follicular culture on
      steroidogenesis, in vitro oocyte maturation, and embryo development in mice.
AB  - Insulin-like growth factor-I (IGF-I) is involved in the regulation of ovarian
      follicular development and has been shown to potentiate the FSH responsiveness of
      granulosa cells from preantral follicles. The aim of the present study was to
      investigate the effect of IGF-I during preantral follicular culture on
      steroidogenesis, subsequent oocyte maturation, fertilization, and embryo
      development in mice. Preantral follicles were isolated mechanically and cultured
      for 12 days in a simplified culture medium supplemented with 1% fetal calf serum,
      recombinant human FSH, transferrin, and selenium. In these conditions, follicles
      were able to grow and produce oocytes that could be matured and fertilized. The
      first experiment analyzed the effect of different concentrations of IGF-I (0, 10,
      50, or 100 ng/ml) added to the culture medium on the follicular survival,
      steroidogenesis, and the oocyte maturation process. The presence of IGF-I during
      follicular growth increased the secretion of estradiol but had no effect on the
      subsequent oocyte survival and maturation rates. In the second experiment, IGF-I
      (0 or 50 ng/ml) was added to the culture medium during follicular growth, oocyte
      maturation, or both, and subsequent oocyte fertilization and embryo development
      rates were evaluated. Oocyte fertilization rates were comparable in the presence
      or absence of IGF-I. However, the blastocyst development rate was enhanced after
      follicular culture in the presence of IGF-I. Moreover, the total cell number of
      the blastocysts observed after differential labeling staining was also higher
      when follicles were cultured or matured in the presence of IGF-I.

PMID- 14960489
TI  - Episodic gonadotropin secretion in the mature fowl: serial blood sampling from
      unrestrained male broiler breeders (Gallus domesticus).
AB  - Forty-week-old male broiler breeders were used in two experiments. Males were
      reared as recommended by the breeder, housed in individual cages, and cannulated
      to facilitate blood sampling. In experiment 1, blood samples were collected at 10
      min intervals for 4 h commencing the day of cannulation (Day 0) and for 12 h on
      each of Days 1 and 2. In experiment 2, blood samples were collected at 10-min
      intervals for 8 h on Day 1. After centrifugation, plasma was stored at -20
      degrees C until LH, FSH (experiment 1 and 2), testosterone, and corticosterone
      (experiment 1) concentrations were determined by RIA. Different statistical
      methods used to identify hormone secretion profiles revealed a characteristic
      pulsatile pattern of LH and FSH in plasma. However, LH pulses were more frequent
      and had greater amplitude than FSH pulses. Less than 32% of the FSH pulses were
      associated with LH episodes. Conversely, the association between LH and
      testosterone pulses averaged 83% in birds with testis weight greater than 10 g.
      Concentrations of corticosterone tended to increase after cannulation and
      remained elevated for only 3-4 h. Our data indicate that LH, FSH, and
      testosterone secretion is pulsatile in male broiler breeders. Additionally, LH
      pulses are associated with testosterone episodes but not with FSH pulses. The
      pulsatile pattern of FSH secretion, which is unique from those of LH, in adult
      males suggests that FSH secretion is independently regulated in the adult male
      fowl.

PMID- 14960490
TI  - Transcription factor expression patterns in bovine in vitro-derived embryos prior
      to maternal-zygotic transition.
AB  - Maternal-zygotic transition (MZT) is a complex phenomenon characterized by the
      initiation of transcription in the embryo and the replacement of maternal mRNA
      with embryonic mRNA. In order for this to occur, transcriptional activation
      requires various factors and conditions. Our hypothesis is that the lack of
      transcription in the bovine pre-MZT embryo is due, in part, to an incomplete or
      dormant transcriptional apparatus. Therefore, in accordance with this hypothesis,
      functioning transcriptional mechanisms should appear in the eight-cell bovine
      embryo to facilitate embryonic transcription during the MZT. With this in mind,
      we examined the presence of selected transcription factors during preimplantation
      embryo development to establish how their transcript levels change in bovine pre
      MZT embryos. To achieve this goal, real-time reverse transcription-polymerase
      chain reaction was used to quantify the mRNA level of several different
      transcription factors (YY1, HMGA1, RY-1, P300, CREB, YAP65, HMGN1, HMGB1, NFAR,
      OCT-4, TEAD2, ATF-1, HMGN2, MSY2, and TBP) in germinal vesicle (GV) and metaphase
      II (MII) bovine oocytes and in two-, four-, eight-cell, and blastocyst stage
      embryos produced in vitro. Our results demonstrate that all genes examined can be
      grouped into five different categories according to their mRNA expression
      patterns at the developmental stages observed. To summarize, all transcription
      factors studied were present in pre-MZT embryos and the expression pattern of
      many of them suggest a potential role in MZT.

PMID- 14960491
TI  - Retinoid-sensitive steps in steroidogenesis in fetal and neonatal rat testes: in
      vitro and in vivo studies.
AB  - Retinoic acid (RA) was recently shown to modify testosterone secretion of the
      fetal testis in vitro. We characterized this effect by culturing rat testes
      explanted at various ages, from Fetal Day 14.5 to Postnatal Day 3. In basal
      medium, RA inhibited, in a dose-dependent manner, both basal and acute LH
      stimulated testosterone secretion by testes explanted on Fetal Days 14.5, 15.5,
      and 16.5. It had no effect on testes from older animals. The negative effect of
      RA did not result from a diminution in the number of Leydig cells but from a
      decrease in P450c17 mRNA levels and in LH-stimulated cAMP production. However,
      the RA-induced decrease in P450C17 mRNA levels was also observed with neonatal
      testes, suggesting that this enzymatic step is no longer rate limiting at this
      developmental stage. To study the physiological relevance of RA effects, we used
      fetuses and neonates issued from mothers fed a vitamin A-deficient (VAD) diet,
      resulting in a threefold decrease of plasma retinol concentration. On Fetal Day
      18.5 and on Posnatal Day 3, testosterone secretion by the testis ex vivo was
      significantly increased in VAD animals. This shows that the endogenous retinol
      inhibits differentiation and/or function of fetal Leydig cells before Fetal Day
      18.5 and is required for the normal regression of fetal Leydig cell function that
      occurs after Fetal Day 18.5. In conclusion, our results show that retinoids play
      a negative role on the steroidogenic activity during the differentiation of rat
      fetal Leydig cells.

PMID- 14960492
TI  - Overlapping mechanisms function to establish transcriptional quiescence in the
      embryonic Drosophila germline.
AB  - In Drosophila melanogaster, the germline precursor cells, i.e. pole cells, are
      formed at the posterior of the embryo. As observed for newly formed germ cells in
      many other eukaryotes, the pole cells are distinguished from the soma by their
      transcriptional quiescence. To learn more about the mechanisms involved in
      establishing quiescence, we ectopically expressed a potent transcriptional
      activator, Bicoid (Bcd), in pole cells. We find that Bcd overrides the machinery
      that downregulates transcription, and activates not only its target gene
      hunchback but also the normally female specific Sex-lethal promoter, Sxl-Pe, in
      the pole cells of both sexes. Unexpectedly, the terminal pathway gene torso-like
      is required for Bcd-dependent transcription. However, terminal signaling is known
      to be attenuated in pole cells, and this raises the question of how this is
      accomplished. We present evidence indicating that polar granule component (pgc)
      is required to downregulate terminal signaling in early pole cells. Consistently,
      pole cells compromised for pgc function exhibit elevated levels of activated MAP
      kinase and premature transcription of the target gene tailless (tll).
      Furthermore, pgc is required to establish a repressive chromatin architecture in
      pole cells.

PMID- 14960493
TI  - Cooperation between sonic hedgehog and fibroblast growth factor/MAPK signalling
      pathways in neocortical precursors.
AB  - Sonic hedgehog (SHH) and fibroblast growth factor 2 (FGF2) can both induce
      neocortical precursors to express the transcription factor OLIG2 and generate
      oligodendrocyte progenitors (OLPs) in culture. The activity of FGF2 is unaffected
      by cyclopamine, which blocks Hedgehog signalling, demonstrating that the FGF
      pathway to OLP production is Hedgehog independent. Unexpectedly, SHH-mediated OLP
      induction is blocked by PD173074, a selective inhibitor of FGF receptor (FGFR)
      tyrosine kinase. SHH activity also depends on mitogen-activated protein kinase
      (MAPK) but SHH does not itself activate MAPK. Instead, constitutive activity of
      FGFR maintains a basal level of phosphorylated MAPK that is absolutely required
      for the OLIG2- and OLP-inducing activities of SHH. Stimulating the MAPK pathway
      with a retrovirus encoding constitutively active RAS shows that the requirement
      for MAPK is cell-autonomous, i.e. MAPK is needed together with SHH signalling in
      the cells that become OLPs.

PMID- 14960494
TI  - Contribution of Hox genes to the diversity of the hindbrain sensory system.
AB  - The perception of environmental stimuli is mediated through a diverse group of
      first-order sensory relay interneurons located in stereotypic positions along the
      dorsoventral (DV) axis of the neural tube. These interneurons form contiguous
      columns along the anteroposterior (AP) axis. Like neural crest cells and
      motoneurons, first-order sensory relay interneurons also require specification
      along the AP axis. Hox genes are prime candidates for providing this information.
      In support of this hypothesis, we show that distinct combinations of Hox genes in
      rhombomeres (r) 4 and 5 of the hindbrain are required for the generation of
      precursors for visceral sensory interneurons. As Hoxa2 is the only Hox gene
      expressed in the anterior hindbrain (r2), disruption of this gene allowed us to
      also demonstrate that the precursors for somatic sensory interneurons are under
      the control of Hox genes. Surprisingly, the Hox genes examined are not required
      for the generation of proprioceptive sensory interneurons. Furthermore, the
      persistence of some normal rhombomere characteristics in Hox mutant embryos
      suggests that the loss of visceral and somatic sensory interneurons cannot be
      explained solely by changes in rhombomere identity. Hox genes may thus directly
      regulate the specification of distinct first-order sensory relay interneurons
      within individual rhombomeres. More generally, these findings contribute to our
      understanding of how Hox genes specifically control cellular diversity in the
      developing organism

PMID- 14960495
TI  - Specification of vertebral identity is coupled to Notch signalling and the
      segmentation clock.
AB  - To further analyse requirements for Notch signalling in patterning the paraxial
      mesoderm, we generated transgenic mice that express in the paraxial mesoderm a
      dominant-negative version of Delta1. Transgenic mice with reduced Notch activity
      in the presomitic mesoderm as indicated by loss of Hes5 expression were viable
      and displayed defects in somites and vertebrae consistent with known roles of
      Notch signalling in somite compartmentalisation. In addition, these mice showed
      with variable expressivity and penetrance alterations of vertebral identities
      resembling homeotic transformations, and subtle changes of Hox gene expression in
      day 12.5 embryos. Mice that carried only one functional copy of the endogenous
      Delta1 gene also showed changes of vertebral identities in the lower cervical
      region, suggesting a previously unnoticed haploinsufficiency for Delta1.
      Likewise, in mice carrying a null allele of the oscillating Lfng gene, or in
      transgenic mice expressing Lfng constitutively in the presomitic mesoderm,
      vertebral identities were changed and numbers of segments in the cervical and
      thoracic regions were reduced, suggesting anterior shifts of axial identity.
      Together, these results provide genetic evidence that precisely regulated levels
      of Notch activity as well as cyclic Lfng activity are critical for positional
      specification of the anteroposterior body axis in the paraxial mesoderm.

PMID- 14960496
TI  - Roles for p53 and p73 during oligodendrocyte development.
AB  - Oligodendrocytes make myelin in the vertebrate central nervous system (CNS). They
      develop from oligodendrocyte precursor cells (OPCs), most of which divide a
      limited number of times before they stop and differentiate. OPCs can be purified
      from the developing rat optic nerve and stimulated to proliferate in serum-free
      culture by PDGF. They can be induced to differentiate in vitro by either thyroid
      hormone (TH) or PDGF withdrawal. It was shown previously that a dominant-negative
      form of p53 could inhibit OPC differentiation induced by TH but not by PDGF
      withdrawal, suggesting that the p53 family of proteins might play a part in TH
      induced differentiation. As the dominant-negative p53 used inhibited all three
      known p53 family members - p53, p63 and p73 - it was uncertain which family
      members are important for this process. Here, we provide evidence that both p53
      and p73, but not p63, are involved in TH-induced OPC differentiation and that p73
      also plays a crucial part in PDGF-withdrawal-induced differentiation. This is the
      first evidence for a role of p73 in the differentiation of a normal mammalian
      cell.

PMID- 14960497
TI  - Potassium channel antibody-associated encephalopathy: a potentially immunotherapy
      responsive form of limbic encephalitis.
AB  - Patients presenting with subacute amnesia are frequently seen in acute
      neurological practice. Amongst the differential diagnoses, herpes simplex
      encephalitis, Korsakoff's syndrome and limbic encephalitis should be considered.
      Limbic encephalitis is typically a paraneoplastic syndrome with a poor prognosis;
      thus, identifying those patients with potentially reversible symptoms is
      important. Voltage-gated potassium channel antibodies (VGKC-Ab) have recently
      been reported in three cases of reversible limbic encephalitis. Here we review
      the clinical, immunological and neuropsychological features of 10 patients (nine
      male, one female; age range 44-79 years), eight of whom were identified in two
      centres over a period of 15 months. The patients presented with 1-52 week
      histories of memory loss, confusion and seizures. Low plasma sodium
      concentrations, initially resistant to treatment, were present in eight out of
      10. Brain MRI at onset showed signal change in the medial temporal lobes in eight
      out of 10 cases. Paraneoplastic antibodies were negative, but VGKC-Ab ranged from
      450 to 5128 pM (neurological and healthy controls <100 pM). CSF oligoclonal bands
      were found in only one, but bands matched with those in the serum were found in
      six other patients. VGKC-Abs in the CSF, tested in five individuals, varied
      between <1 and 10% of serum values. Only one patient had neuromyotonia, which was
      excluded by electromyography in seven of the others. Formal neuropsychology
      testing showed severe and global impairment of memory, with sparing of general
      intellect in all but two patients, and of nominal functions in all but one.
      Variable regimes of steroids, plasma exchange and intravenous immunoglobulin were
      associated with variable falls in serum VGKC-Abs, to values between 2 and 88% of
      the initial values, together with marked improvement of neuropsychological
      functioning in six patients, slight improvement in three and none in one. The
      improvement in neuropsychological functioning in seven patients correlated
      broadly with the fall in antibodies. However, varying degrees of cerebral atrophy
      and residual cognitive impairment were common. Over the same period, only one
      paraneoplastic case of limbic encephalitis was identified between the two main
      centres. Thus, VGKC-Ab-associated encephalopathy is a relatively common form of
      autoimmune, non-paraneoplastic, potentially treatable encephalitis that can be
      diagnosed by a serological test. Establishing the frequency of this new syndrome,
      the full range of clinical presentations and means of early recognition, and
      optimal immunotherapy, should now be the aim.

PMID- 14960498
TI  - Synthetic disialylgalactose immunoadsorbents deplete anti-GQ1b antibodies from
      autoimmune neuropathy sera.
AB  - Acute and chronic autoimmune neuropathies, including Guillain-Barre syndromes
      (GBS) are often characterized by the presence of autoantibodies that react with
      neural gangliosides. Evidence from human and animal studies indicates that anti
      ganglioside antibodies play a primary neuropathogenic role, and their rapid
      elimination from the circulation through specific immunoadsorption therapy thus
      has the potential to ameliorate the course of the disease. Here we have tested
      this therapeutic principle in the Miller Fisher variant of GBS that is associated
      serologically with acute phase anti-GQ1b ganglioside immunoglobulin G (IgG)
      antibodies, and in chronic ataxic neuropathies associated with persistently
      elevated immunoglobulin M (IgM) antibodies that react with GQ1b, GD3 and other
      disialylated gangliosides. Human and mouse anti-GQ1b IgG and IgM antibodies may
      also react with GD3, suggesting the shared terminal disialoside epitope could be
      involved in antibody binding. We thus synthesized the terminal trisaccharide,
      NeuAc(alpha2-8)NeuAc(alpha2-3)Gal common to GQ1b and GD3, and conjugated it to
      bovine serum albumin (BSA). This disialylgalactose glycoconjugate (DSG-BSA) binds
      anti-GQ1b antibodies in 32/58 (55%) human sera containing IgG or IgM anti-GQ1b
      antibodies at titres up to 1/130 000; it also binds a wide range of mouse
      monoclonal anti-GQ1b and -GD3 antibodies. When conjugated to Sepharose as mock
      therapeutic immmunoaffinity columns, the immobilized trisaccharide (DSG
      Sepharose) eliminates anti-GQ1b antibodies from positive sera in proportion to
      their level of binding to DSG-BSA. Oligosaccharide-specific immunoadsorption
      therapy thus provides a new therapeutic approach to anti-GQ1b antibody-associated
      syndromes that could be applied to clinical practice. Furthermore, modification
      of the immobilized oligosaccharide epitopes to incorporate other glycan
      structures may allow this approach to be adapted to other forms of autoimmune
      neuropathy associated with uniform anti-glycolipid antibody profiles.

PMID- 14960499
TI  - Pain catastrophizing and neural responses to pain among persons with
      fibromyalgia.
AB  - Pain catastrophizing, or characterizations of pain as awful, horrible and
      unbearable, is increasingly being recognized as an important factor in the
      experience of pain. The purpose of this investigation was to examine the
      association between catastrophizing, as measured by the Coping Strategies
      Questionnaire Catastrophizing Subscale, and brain responses to blunt pressure
      assessed by functional MRI among 29 subjects with fibromyalgia. Since
      catastrophizing has been suggested to augment pain perception through enhanced
      attention to painful stimuli, and heightened emotional responses to pain, we
      hypothesized that catastrophizing would be positively associated with activation
      in structures believed to be involved in these aspects of pain processing. As
      catastrophizing is also strongly associated with depression, the influence of
      depressive symptomatology was statistically removed. Residual scores of
      catastrophizing controlling for depressive symptomatology were significantly
      associated with increased activity in the ipsilateral claustrum (r = 0.51, P <
      0.05), cerebellum (r = 0.43, P < 0.05), dorsolateral prefrontal cortex (r = 0.47,
      P < 0.05), and parietal cortex (r = 0.41, P < 0.05), and in the contralateral
      dorsal anterior cingulate gyrus (ACC; r = 0.43, P < 0.05), dorsolateral
      prefrontal cortex (r = 0.41, P < 0.05), medial frontal cortex (r = 0.40, P <
      0.05) and lentiform nuclei (r = 0.40, P < 0.05). Analysis of subjects classified
      as high or low catastrophizers, based on a median split of residual
      catastrophizing scores, showed that both groups displayed significant increases
      in ipsilateral secondary somatosensory cortex (SII), although the magnitude of
      activation was twice as large among high catastrophizers. Both groups also had
      significant activations in contralateral insula, SII, primary somatosensory
      cortex (SI), inferior parietal lobule and thalamus. High catastrophizers
      displayed unique activation in the contralateral anterior ACC, and the
      contralateral and ipsilateral lentiform. Both groups also displayed significant
      ipsilateral activation in SI, anterior and posterior cerebellum, posterior
      cingulate gyrus, and superior and inferior frontal gyrus. These findings suggest
      that pain catastrophizing, independent of the influence of depression, is
      significantly associated with increased activity in brain areas related to
      anticipation of pain (medial frontal cortex, cerebellum), attention to pain
      (dorsal ACC, dorsolateral prefrontal cortex), emotional aspects of pain
      (claustrum, closely connected to amygdala) and motor control. These results
      support the hypothesis that catastrophizing influences pain perception through
      altering attention and anticipation, and heightening emotional responses to pain.
      Activation associated with catastrophizing in motor areas of the brain may
      reflect expressive responses to pain that are associated with greater pain
      catastrophizing.

PMID- 14960500
TI  - Presynaptic mechanisms of motor fluctuations in Parkinson's disease: a
      probabilistic model.
AB  - Levodopa-treated Parkinson's disease is often complicated by the occurrence of
      motor fluctuations, which can be predictable ('wearing-off') or unpredictable
      ('on-off'). In contrast, untreated dopa-responsive dystonia (DRD) is usually
      characterized by predictable diurnal fluctuation. The pathogenesis of motor
      fluctuations in treated Parkinson's disease and diurnal fluctuation in untreated
      DRD is poorly understood. We have developed a mathematical model indicating that
      all these fluctuations in motor function can be explained by presynaptic
      mechanisms. The model is predicated upon the release of dopamine being subject to
      probabilistic variations in the quantity of dopamine released by exocytosis of
      vesicles. Specifically, we propose that the concentration of intravesicular
      dopamine undergoes dynamic changes according to a log-normal distribution that is
      associated with different probabilities of release failure. Changes in two
      parameters, (i) the proportion of vesicles that undergo exocytosis per unit of
      time and (ii) the proportion of dopamine subject to re-uptake from the synapse,
      allowed us to model different curves of levodopa response, for the same degree of
      nigrostriatal damage in Parkinson's disease. The model predicts the following
      periods of levodopa clinical benefit: 4 h for stable responders, 3 h for wearing
      off fluctuators, and 1.5 h for on-off fluctuators. The model also predicts that
      diurnal fluctuation in untreated DRD should occur some 8 h after getting up in
      the morning. All these results fit well with clinical observations. Additionally,
      we calculated the probability of obtaining a second ON period after a single dose
      of levodopa in Parkinson's disease (the 'yo-yoing' phenomenon). The model shows
      that the yo-yoing phenomenon depends on how fast the curve crosses the threshold
      that separates ON and OFF states, which explains why this phenomenon is virtually
      exclusive to patients with on-off fluctuations. The model supports the idea that
      presynaptic mechanisms play a key role in both short-duration and long-duration
      responses encountered in Parkinson's disease. Dyskinesias may also be explained
      by the same mechanisms.

PMID- 14960501
TI  - Trends in survival and cause of death in Danish patients with multiple sclerosis.
AB  - The Danish Multiple Sclerosis Registry contains information about all Danish
      patients in whom multiple sclerosis has been diagnosed since 1948. The purpose of
      this study was to analyse trends in survival and causes of death of these
      patients and to compare them with those of the general population. The study
      comprised all patients with onset in the period 1949-1996. All case records were
      validated and classified according to standardized diagnostic criteria. Data on
      emigration and death were obtained by record linkage to official registers. The
      end of follow-up was 1 January 2000 for emigration and death, and 1 January 1999
      for cause-specific deaths. Standardized mortality ratios and excess death rates
      were calculated for various causes of death and periods after multiple sclerosis
      onset, and time trends in survival probability were analysed by Cox regression.
      The study comprised 9881 patients, of whom 4254 had died before end of follow-up.
      The median survival time from onset was approximately 10 years shorter for
      multiple sclerosis patients than for the age-matched general population, and
      multiple sclerosis was associated with an almost threefold increase in the risk
      for death. According to death certificates, more than half (56.4%) of the
      patients had died from multiple sclerosis. They also had excess mortality rates
      from other diseases, except cancer, and from accidents and suicide. The
      probability for survival improved significantly during the observation period.
      Thus, the 10-year excess mortality was almost halved in comparison with that in
      the middle of the 1900s.

PMID- 14960502
TI  - Event-related beta desynchronization in human subthalamic nucleus correlates with
      motor performance.
AB  - Although the basal ganglia play an important role in self-generated movement,
      their involvement in externally paced voluntary movement is less clear. We
      recorded local field potentials (LFPs) from the region of the subthalamic nuclei
      of eight patients with Parkinson's disease during the performance of a warned
      reaction time task in which an imperative cue instructed the subject to move or
      not to move. In 'go' trials, LFP activity in the beta frequency band (
      approximately 20 Hz) decreased prior to movement, with an onset latency that
      strongly correlated with mean reaction time across patients. This was followed by
      a late post-movement increase in beta power. In contrast, in 'nogo' trials the
      beta power drop following imperative signals was prematurely terminated compared
      with go trials and reversed into an early beta power increase. These differences
      were manifest as power increases when go trials were subtracted from nogo trials.
      In six patients these relative beta power increases in nogo-go difference trials
      were of shorter latency than the respective reaction time. The findings suggest
      that, firstly, the subthalamic nucleus is involved in the preparation of
      externally paced voluntary movements in humans and, secondly, the degree of
      synchronization of subthalamic nucleus activity in the beta band may be an
      important determinant of whether motor programming and movement initiation is
      favoured or suppressed.

PMID- 14960503
TI  - Human eye fields in the frontal lobe as studied by epicortical recording of
      movement-related cortical potentials.
AB  - We studied the generator location of premovement subcomponents of movement
      related cortical potentials (MRCPs) [Bereitschaftspotential (BP), negative slope
      (NS') and motor potential (MP)] associated with voluntary, self-paced horizontal
      saccade in the human frontal lobe. Self-paced horizontal saccade, wrist (or
      middle finger) extension and foot dorsiflexion were employed in 10 patients
      (lateral surface of the frontal lobe in seven and mesial in three) as part of the
      presurgical evaluation, and data of five patients (lateral in four and mesial in
      three) were used in the final analysis. On the lateral frontal lobe, the maximum
      BP, NS' or MP with horizontal saccade was seen at or 1-2 cm rostral to the hand,
      arm or face area of the primary motor cortex (MI) in all four subjects
      investigated. This area exactly corresponded to the frontal eye field (FEF)
      identified by electrical stimulation. The amplitude of MRCPs with saccade was
      smaller than that with hand movements. On the mesial surface, within the
      supplementary motor area (SMA) proper, BP and/or NS' for horizontal saccade was
      located 1-2 cm rostral to that for hand and foot movements. BP and/or NS'
      delineated the supplementary eye field (SEF) at the rostral part of the SMA
      proper, and SEF partly overlapped with the hand and foot areas of the SMA proper.
      At the area just rostral to the vertical anterior commissure line and/or the pre
      SMA defined by electrical stimulation, BP and/or NS' was seen invariably,
      regardless of the sites of movements, and in contrast with the SMA proper, there
      was no somatotopic representation. No clear MPs were elicited by eye movements on
      the mesial surface. In one of the two subjects whose MRCPs with horizontal
      saccade were recorded simultaneously from the lateral and mesial surfaces of the
      frontal lobe, BP from the SEF and pre-SMA preceded that from the FEF. It is
      concluded that MRCPs with horizontal saccade are useful for defining the FEF, SEF
      and pre-SMA, and that the SEF and pre-SMA become active in preparation for
      horizontal saccade earlier than the FEF.

PMID- 14960504
TI  - Effects of low dose ramipril on cardiovascular and renal outcomes in patients
      with type 2 diabetes and raised excretion of urinary albumin: randomised, double
      blind, placebo controlled trial (the DIABHYCAR study).
AB  - OBJECTIVE: To investigate whether a low dose of the angiotensin converting enzyme
      (ACE) inhibitor ramipril lowers cardiovascular and renal events in patients with
      type 2 diabetes who have microalbuminuria or proteinuria. DESIGN: Randomised,
      double blind, parallel group trial comparing ramipril (1.25 mg/day) with placebo
      (on top of usual treatment) for cardiovascular and renal outcomes for at least
      three years. SETTING: Multicentre, primary care study conducted mostly by general
      practitioners in 16 European and north African countries. PARTICIPANTS: 4912
      patients with type 2 diabetes aged >50 years who use oral antidiabetic drugs and
      have persistent microalbuminuria or proteinuria (urinary albumin excretion > or =
      20 mg/l in two consecutive samples), and serum creatinine < or = 150 micromol/l.
      MAIN OUTCOME MEASURES: The primary outcome measure was the combined incidence of
      cardiovascular death, non-fatal myocardial infarction, stroke, heart failure
      leading to hospital admission, and end stage renal failure. RESULTS: Participants
      were followed for 3 to 6 (median 4) years. There were 362 primary events among
      the 2443 participants taking ramipril (37.8 per 1000 patient years) and 377
      events among the 2469 participants taking placebo (38.8 per 1000 patient years;
      hazard ratio 1.03 (95% confidence interval 0.89 to 1.20, P = 0.65)). None of the
      components of the primary outcome was reduced. Ramipril lowered systolic and
      diastolic blood pressures (by 2.43 and 1.06 mm Hg respectively after two years)
      and favoured regression from microalbuminuria (20-200 mg/l) or proteinuria (>
      200mg/l) to normal level (< 20 mg/l) or microalbuminuria (P < 0.07) in 1868
      participants who completed the study. CONCLUSIONS: Low dose (1.25 mg) ramipril
      once daily has no effect on cardiovascular and renal outcomes of patients with
      type 2 diabetes and albuminuria, despite a slight decrease in blood pressure and
      urinary albumin. The cardiovascular benefits of a daily higher dose (10 mg)
      ramipril observed elsewhere are not found with an eightfold lower daily dose.

PMID- 14960505
TI  - Progress report.

PMID- 14960506
TI  - Fibrosis progression in chronic hepatitis C virus infection.
AB  - Chronic hepatitis C virus infection is typically characterised by slowly
      progressive hepatic fibrosis. However, it is recognised that some patients do not
      progress while others rapidly develop significant fibrosis. Here, we review
      studies that have assessed factors that could influence this rate of fibrotic
      progression.

PMID- 14960507
TI  - Extracolonic polyposis in familial adenomatous polyposis: so near and yet so far.

PMID- 14960508
TI  - PDX1 homeobox protein expression in pseudopyloric glands and gastric carcinomas.
AB  - BACKGROUND AND AIMS: Although it has been reported that intestinal metaplasia
      implicated in gastric carcinogenesis is induced by the ParaHox gene CDX2, it is
      unclear which genes are responsible for the formation of pseudopyloric glands and
      whether they play a role in gastric carcinogenesis. Pancreatic-duodenal homeobox
      1 (PDX1) is also a ParaHox gene which contributes to the genesis and development
      of the pancreas, duodenum, and antrum. To clarify its significance for the
      formation of pseudopyloric glands and gastric carcinogenesis, we investigated
      expression of PDX1 and mucin in gastric carcinomas and surrounding mucosa.
      METHODS: Gastric carcinoma tissues from 95 patients were used for
      immunohistochemical analyses of PDX1, and mucins MUC6 and MUC5AC. RESULTS: PDX1
      was found to be frequently expressed in pseudopyloric glands and intestinal
      metaplasia. MUC6 was more abundant than MUC5AC in pseudopyloric glands while
      higher levels of MUC5AC than MUC6 were evident in intestinal metaplasia. The
      frequency of PDX1 positive reactivity was higher in differentiated type
      carcinomas (39/43, 90.7%) and T1 carcinomas (42/43, 97.7%) than in
      undifferentiated type (33/52, 63.5%) and T2-4 (30/52, 57.7%) carcinomas. PDX1 and
      MUC6 double positive expression was observed in carcinomas, respectively,
      including the corpus, and also correlated with histological type and depth of
      invasion. In contrast, no link was apparent between PDX1 and MUC5AC double
      positive reactivity and histological type. CONCLUSION: Our study suggests that
      PDX1 plays an important role in the development of pseudopyloric glands, and that
      pseudopyloric glands may reflect a condition associated with gastric
      carcinogenesis.

PMID- 14960509
TI  - Menetrier disease.

PMID- 14960510
TI  - Effect of peroxisome proliferator activated receptor gamma ligands on growth and
      gene expression profiles of gastric cancer cells.
AB  - BACKGROUND AND AIMS: Although peroxisome proliferator activated receptor gamma
      (PPARgamma) agonists have been implicated in differentiation and growth
      inhibition of cancer cells, the potential therapeutic and chemopreventive effects
      on gastric cancer are poorly defined. We examined the in vitro and in vivo
      effects of PPARgamma ligands on growth of gastric cancer, and the effect of
      PPARgamma activation on expression of cyclooxygenase 2 (COX-2) and cancer related
      genes. METHODS: Gastric cell lines (MKN28 and MKN45) were treated with two
      specific PPARgamma ligands: ciglitazone and 15-deoxy-Delta(12,)(14)-prostaglandin
      J(2). Cell growth was determined by bromodeoxyuridine incorporation assay and
      apoptosis was measured by DNA fragmentation. Expression of COX-2 was determined
      by western blot and real time quantitative polymerase chain reaction (PCR).
      Expression profiles of cancer related genes were screened with cDNA array. In
      vivo growth of implanted MKN45 cells in nude mice was monitored after oral
      treatment with rosiglitazone. RESULTS: PPARgamma ligands suppressed the in vitro
      growth of MKN45 cells in a dose dependent manner whereas prostacyclin, a
      PPARdelta agonist, had no growth inhibitory effect. Growth inhibition was more
      pronounced in MKN45 cells, which was accompanied by DNA fragmentation and
      downregulation of COX-2. Screening by cDNA microarray showed that PPARgamma
      ligand treatment was associated with upregulation of bad and p53, and
      downregulation of bcl-2, bcl-xl, and cyclin E1 in MKN45 cells, which was
      confirmed by quantitative real time PCR. In contrast, MKN28 cells with lower
      PPARgamma and COX-2 expression levels had lower growth inhibitory responses to
      PPARgamma ligands. Microarray experiments only showed induction of the bad gene
      in MKN28 cells. In vivo growth of MKN45 cells in nude mice was retarded by
      rosiglitazone. Mean tumour volume in rosiglitazone treated mice was significantly
      lower than controls at six weeks (p = 0.019) and seven weeks (p = 0.001) after
      treatment. CONCLUSIONS: PPARgamma ligands suppress both in vitro and in vivo
      growth of gastric cancer and may play a major role in cancer therapy and
      prevention.

PMID- 14960512
TI  - An interleukin 12 p40-IgG2b fusion protein abrogates T cell mediated
      inflammation: anti-inflammatory activity in Crohn's disease and experimental
      colitis in vivo.
AB  - BACKGROUND AND AIMS: Interleukin-12 (IL-12), a p35/p40 heterodimer, plays a
      pivotal role in the immune response in Crohn's disease (CD). Since IL-12 p40
      dimers act as IL-12 antagonists, we assayed p40 dimer proteins to modulate
      chronic intestinal inflammation. METHODS: We generated a fusion protein
      consisting of the IL-12(p40) subunit fused to the constant region of IgG2b. IL
      12(p40)-IgG2b was tested in a murine 2,4,6,-trinitrobenzene sulphonic acid (TNBS)
      colitis model and in lamina propria mononuclear cells (LPMNC) from patients with
      CD in vitro. RESULTS: Dimeric IL-12(p40)-IgG2b fusion protein bound specifically
      to the IL-12 receptor. In concentrations <10(-7) M, it acted as an IL-12
      antagonist as it inhibited interferon gamma (IFN-gamma) secretion, suppressed
      proliferation, and increased apoptosis of LPMNC from patients with CD. However,
      in concentrations >10(-6) M, IL-12(p40)-IgG2b increased IFN-gamma secretion and
      lymphocyte proliferation thereby acting as an IL-12 agonist. In TNBS colitic
      mice, IL-12(p40)-IgG2b decreased mortality (10% v 68%), prevented body weight
      loss, reduced tumour necrosis factor alpha, and increased IL-10 secretion.
      CONCLUSIONS: The IL-12(p40)-IgG2b fusion protein has dichotomic properties as a
      specific IL-12 antagonist and selective repressor of mucosal inflammation at low
      concentration and as an IL-12 agonist at high concentration.

PMID- 14960513
TI  - Microscopic colitis: a common diarrhoeal disease. An epidemiological study in
      Orebro, Sweden, 1993-1998.
AB  - BACKGROUND: Microscopic colitis, including collagenous colitis and lymphocytic
      colitis, mainly affects middle aged and older subjects, with a female
      predominance in collagenous colitis. The diseases have previously been regarded
      as rare. We present an epidemiological study of microscopic colitis in a well
      defined Swedish population. METHODS: Patients were retrospectively searched for
      in colonoscopy reports of those who had a colonoscopy in the period 1993-1998 for
      non-bloody diarrhoea. All colonic mucosal biopsies were reassessed using strict
      diagnostic criteria. RESULTS: Biopsies from 1018 patients were reassessed. Fifty
      one (45 female) collagenous colitis patients and 46 (31 female) lymphocytic
      colitis patients were diagnosed. Median age at diagnosis was 64 years in
      collagenous colitis and 59 years in lymphocytic colitis. The mean annual
      incidence of collagenous colitis was 4.9/10(5) inhabitants (95% confidence
      interval (CI) 3.6-6.2/10(5)) and of lymphocytic colitis 4.4/10(5) inhabitants
      (95% CI 3.1-5.7/10(5)). The annual incidence of collagenous colitis increased
      from 3.7/10(5) in 1993-1995 to 6.1/10(5) in 1996-1998 (difference 2.4/10(5) (95%
      CI -0.3-5.1/10(5))) whereas the incidence of lymphocytic colitis increased from
      3.1/10(5) to 5.7/10(5) (difference 2.6/10(5) (95% CI 0.1-5.2/10(5))).
      CONCLUSIONS: The annual incidences of collagenous colitis and lymphocytic colitis
      are higher than considered previously and are now equal to the incidence of
      Crohn's disease in Sweden, and combined rates approach the incidence of
      ulcerative colitis. Microscopic colitis was diagnosed in 10% of all patients with
      non-bloody diarrhoea referred for colonoscopy and in almost 20% of those older
      than 70 years.

PMID- 14960514
TI  - Appendicectomy has no beneficial effect on admission rates in patients with
      ulcerative colitis.
AB  - BACKGROUND AND AIMS: Those who have had an appendicectomy have a reduced risk of
      developing ulcerative colitis. However, the effect of appendicectomy on disease
      activity in patients with ulcerative colitis has not been established. METHODS:
      We used the Danish National Patient Registry to identify all incident cases of
      ulcerative colitis in Denmark during the period 1981 to 1999. Of these, 202 had
      an appendicectomy after their first admission with ulcerative colitis. In these
      patients, we compared the incidence rate of hospitalisations with ulcerative
      colitis as first diagnosis during the period between the onset of ulcerative
      colitis and appendicectomy, with the rate of such hospitalisations after
      appendicectomy. To adjust for the clinical course of ulcerative colitis unrelated
      to appendicectomy, we extracted a reference cohort (n = 808), matched to the
      index subjects with respect to age, sex, and year of first admission, but with an
      intact appendix. RESULTS: The rate of admission with ulcerative colitis as first
      diagnosis decreased by 47% after appendicectomy (rate ratio 0.53 (95% confidence
      interval (CI) 0.36-0.80)). However, the reference cohort showed a similar decline
      in admission rate (rate ratio 0.51). Thus appendicectomy had no apparent
      beneficial effect on admission rate after adjustment for the clinical course of
      disease unrelated to appendicectomy (adjusted rate ratio 1.05 (95% CI 0.67
      1.67)). CONCLUSIONS: Appendicectomy had no significant beneficial effect on
      admission rates in patients with ulcerative colitis.

PMID- 14960515
TI  - Tumour suppression induced by the macrophage activating lipopeptide MALP-2 in an
      ultrasound guided pancreatic carcinoma mouse model.
AB  - BACKGROUND AND AIM: Carcinoma of the exocrine pancreas has a particularly poor
      prognosis. Therefore, novel therapeutic strategies such as immunotherapy are
      required. Here we investigated the immunomodulatory capacity of macrophage
      activating lipopeptide 2 (MALP-2), which binds to toll-like receptors 2 and 6 and
      induces activation of nuclear factor kappaB in monocytes. This causes the release
      of early stage leucocyte attracting chemokines and proinflammatory cytokines.
      METHODS: MALP-2 was tested in a new orthotopic ultrasound guided pancreatic
      cancer mouse model. This model is close to the biological situation and avoids
      the stress and immunostimulation caused by laparotomy. Cells from the syngeneic,
      highly aggressive, and metastatic cell line Panc 02 were administered
      orthotopically, by ultrasound guidance, to C57bl/6 mice. MALP-2 was administered
      intratumorally or intraperitoneally and tumour growth, immune status, and
      leucocyte infiltration at the tumour site were determined. RESULTS: We showed a
      tumour suppressive effect induced by a single injection of MALP-2. Median
      survival increased from 21 to 30 days (p<0.002). Combining chemotherapy
      (gemcitabine) with MALP-2 treatment caused further prolonged survival (median
      survival 27 days with chemotherapy alone v 37 days for combined treatment;
      p<0.0002). The life prolonging effect was paralleled by a significant increase in
      cytotoxic T cells, restoration of beta2 integrin expression on lymphocytes, and
      high expression of CD45RB on T helper cells. Immunohistochemical stains showed
      strong cytotoxic T lymphocyte and natural killer cell infiltration. CONCLUSIONS:
      In conclusion, in a model of orthotopic pancreatic cancer in mice, we induced a
      tumour suppressive effect by treatment with a synthetic lipopeptide. Treatment
      with MALP-2 could be an option for immunotherapy in pancreatic cancer.

PMID- 14960516
TI  - Enteric neurones modulate the colonic permeability response to luminal bile acids
      in rat colon in vivo.
AB  - BACKGROUND: The mechanisms behind microscopic colitis and exacerbations of
      ulcerative colitis are incompletely understood. It seems highly likely that both
      luminal antigens and bile are involved. The aim of this study was to test the
      hypothesis that bile acids increase colonic mucosal permeability by activating
      enteric neurones. METHOD: The effect of 4 mM deoxycholic acid (DCA) on the
      appearance rate of intravenously administered (3)H-mannitol and (14)C-urea into
      the lumen of the proximal and distal rat colon was measured in vivo and expressed
      as clearance. The nerve blocking agents atropine and hexamethonium were given
      intravenously, and lidocaine was applied onto the serosal surface of the colon,
      before and after DCA exposure RESULTS: DCA markedly increased clearance of the
      permeability probes into the lumen in both colonic segments and also the ratio of
      mannitol/urea clearance, particularly in the distal colon. Pretreatment with
      atropine, hexamethonium, and lidocaine significantly inhibited the increase in
      clearance by approximately 65-80% but did not affect the clearance ratio. In the
      distal colon, the inhibitory effect of lidocaine was not statistically
      significant. Also, administration of atropine and hexamethonium after DCA
      exposure significantly inhibited the DCA effect on clearance of the probes.
      CONCLUSION: The results suggest that in vivo, the permeability increase induced
      by a moderate concentration of bile acid is to a large extent mediated by a
      neural mechanism involving muscarinic and nicotinic receptors. This mechanism may
      be a link between the central nervous system and colonic mucosal barrier
      function, and may be a new target for treatment.

PMID- 14960517
TI  - Behavioural therapy (biofeedback) for solitary rectal ulcer syndrome improves
      symptoms and mucosal blood flow.
AB  - AIMS: The aim of the study was to determine if there is a permanent disorder of
      mucosal blood flow in patients with solitary rectal ulcer syndrome (SRUS) or a
      disorder related to autonomic gut innervation and physiological function that is
      reversible concomitant with successful treatment. Rectal mucosal blood flow was
      used as a validated measure of extrinsic autonomic nerve function. METHODS:
      Sixteen consecutive patients with SRUS (12 women; mean age 35 years) and 26
      healthy controls (17 women; mean age 36 years) were studied. Laser Doppler
      mucosal flowmetry was performed before and after biofeedback treatment. Symptoms
      were documented before and after biofeedback treatment using a standardised
      prospectively applied questionnaire. RESULTS: Twelve of 16 patients (75%)
      reported subjective symptomatic improvement after treatment. Five of the 16
      patients (31%) had sigmoidoscopic ulcer resolution. Pretreatment rectal mucosal
      blood flow was significantly lower in patients with SRUS compared with controls
      (163 (27) v 186 (14) flux units (FU) (mean (SD)); p<0.01). Biofeedback resulted
      in a significant improvement in rectal mucosal blood flow in subjects who felt
      subjectively better after biofeedback (p = 0.001), from 165 (30) FU to 190 (40)
      FU. CONCLUSION: Gut directed biofeedback is an effective behavioural treatment
      for the majority of patients with SRUS. Mucosal blood flow is reduced to a
      similar level seen in normal transit constipation, suggesting similar impaired
      extrinsic autonomic cholinergic nerve activity. Successful outcome following
      biofeedback is associated with increased rectal mucosal blood flow, suggesting
      that improved extrinsic innervation to the gut may be partially responsible for
      the response to treatment.

PMID- 14960518
TI  - Prognostic significance of microsatellite instability determined by
      immunohistochemical staining of MSH2 and MLH1 in sporadic T3N0M0 colon cancer.
AB  - BACKGROUND: Microsatellite instability (MSI) has been identified as a factor with
      good prognosis and chemosensitivity in stage III C colon cancer. The purpose of
      this study was to evaluate the routine use of immunohistochemical analysis
      (immunohistochemical staining of MSH2 and MLH1) to identify T3N0M0 (stage II)
      colon cancer with MSI and assess the prognostic value of this analysis. The study
      was conducted in a large cohort of patients in a single institution who had a
      curatively resected T3N0M0 colon cancer and were not receiving adjuvant therapy.
      METHODS: Between June 1995 and December 2001, 142 patients (77 females) with a
      mean age of 68 years, suffering from T3N0M0 colon cancer curatively resected and
      not receiving adjuvant therapy, were checked in terms of their follow up status.
      The results of colonoscopy, hepatic ultrasonography, chest x ray, and blood
      carcinoembryological antigen were noted. All tumours were immunohistochemically
      stained for MSH2 and MLH1. Perineural invasion, lymphovascular invasion, and the
      presence of vascular neoplastic emboli were assessed. RESULTS: Twenty four
      patients (17%) had MSI tumours. Patients with MSI and microsatellite stable (MSS)
      tumours did not differ in terms of age, perineural or lymphovascular invasion, or
      the presence of vascular neoplastic emboli. Patients with MSI tumours were more
      frequently female (18/24 v 60/118; p = 0.001) and more frequently suffered from
      right sided cancer (19/24 v 58/118; p<0.001). Patients with MSI tumours exhibited
      significantly better recurrence free survival than those with MSS tumours (p =
      0.02). Cox analysis identified age and MSI determined by immunohistochemistry as
      independent predictive factors of good prognosis (p = 0.009, odds ratio 1.04
      (1.01-1.08); p = 0.04, odds ratio 7.9 (1.05-59.6)). CONCLUSIONS: MSI determined
      by immunohistochemistry is an independent predictive factor of good prognosis in
      T3N0M0 colon cancer. The prognosis for MSI T3N0M0 colon cancer is excellent and
      chemotherapy should not be proposed in these patients as immunohistochemical
      analysis produces rapid results.

PMID- 14960519
TI  - Detecting diminutive colorectal lesions at colonoscopy: a randomised controlled
      trial of pan-colonic versus targeted chromoscopy.
AB  - BACKGROUND: Diminutive and flat colorectal lesions can be difficult to detect
      using conventional colonoscopic techniques. Previous data have suggested that pan
      chromoscopy may improve detection rates. No randomised control trial has been
      performed examining detection rates of such lesions while controlling for
      extubation time and lavage effect. AIM: We conducted a randomised controlled
      trial of pan-colonic chromoscopic colonoscopy for the detection of diminutive and
      flat colorectal lesions while controlling for extubation time and lavage effect.
      METHODS: Consecutive patients attending for routine colonoscopy were randomised
      to either pan-chromoscopy using 0.5% indigo carmine (IC) or targeted chromoscopy
      (control group). A minimum diagnostic extubation time was set at eight minutes
      with controls undergoing a matched volume of saline wash. RESULTS: A total of 260
      patients were randomised; 132 controls and 128 to pan-colonic chromoscopy.
      Extubation times did not differ significantly between the control (median 15
      minutes (range 8-41)) and chromoscopy (median 17 minutes (range 8-39)) groups.
      The volume of IC used in the pan-chromoscopy group (median 68 ml (range 65-90))
      and normal saline used in the control group (69 ml (range 60-93)) did not differ
      significantly. There was a statistically significant difference between the
      groups regarding the total number of adenomas detected (p<0.05) with
      significantly more diminutive (<4 mm) adenomas detected in the pan-chromoscopy
      group (p = 0.03). Pan-chromoscopy diagnosed more diminutive and flat lesions in
      the right colon compared with controls (p<0.05), with more patients with multiple
      adenomas (>3) detected using pan-chromoscopy (p<0.01). Hyperplastic lesions were
      more commonly detected in the pan-chromoscopy group compared with controls
      (p<0.001). More hyperplastic polyps were detected in the left colon (86%
      rectosigmoid) using chromoscopy compared with controls. CONCLUSION: Chromoscopy
      improves the total number of adenomas detected and enhances the detection of
      diminutive and flat lesions. Importantly, eight diminutive lesions had foci of
      high grade dysplasia. Chromoscopy may benefit patients, assuming a high risk of
      colorectal cancer, and help in risk stratification and planning follow up
      colonoscopy intervals.

PMID- 14960520
TI  - Duodenal adenomatosis in familial adenomatous polyposis.
AB  - BACKGROUND: The prevalence of duodenal carcinoma is much higher in familial
      adenomatous polyposis (FAP) than in the background population, and duodenal
      adenomatosis is found in most polyposis patients. AIMS: To describe the long term
      natural history of duodenal adenomatosis in FAP and evaluate if cancer
      prophylactic surveillance of the duodenum is indicated. METHODS: A prospective
      five nation study was carried out in the Nordic countries and the Netherlands.
      PATIENTS: A total of 368 patients were examined by gastroduodenoscopy at two year
      intervals during the period 1990-2001. RESULTS: At the first endoscopy, 238 (65%)
      patients had duodenal adenomas at a median age of 38 years. Median follow up was
      7.6 years. The cumulative incidence of adenomatosis at age 70 years was 90% (95%
      confidence interval (CI) 79-100%), and of Spigelman stage IV 52% (95% CI 28-76%).
      The probability of an advanced Spigelman score increased during the study period
      (p<0.0001) due to an increasing number and size of adenomas. Two patients had
      asymptomatic duodenal carcinoma at their first endoscopy while four developed
      carcinoma during the study at a median age of 52 years (range 26-58). The
      cumulative incidence rate of cancer was 4.5% at age 57 years (95% CI 0.1-8.9%)
      and the risk was higher in patients with Spigelman stage IV at their first
      endoscopy than in those with stages 0-III (p<0.01). CONCLUSIONS: The natural
      course of duodenal adenomatosis has now been described in detail. The high
      incidence and increasing severity of duodenal adenomatosis with age justifies
      prophylactic examination, and a programme is presented for upper gastrointestinal
      endoscopic surveillance.

PMID- 14960521
TI  - Large bowel obstruction due to a benign uterine leiomyoma.

PMID- 14960522
TI  - The Department of Health's "two week standard" for bowel cancer: is it working?
AB  - OBJECTIVE: To determine the effectiveness and efficiency of the Department of
      Health's new general practitioner referral guidelines for bowel cancer. DESIGN:
      One year prospective audit. SETTING: District general hospital serving a
      population of 550 000. SUBJECTS: All patients with bowel cancer; all patients
      referred on the basis of the two week standard and to a routine colorectal
      surgical outpatient clinic. MAIN OUTCOME MEASURES: Proportion of cancers referred
      on the basis of the two week standard and to other colorectal clinics; the
      proportion with the higher risk criteria and their diagnostic yields; stage of
      cancers diagnosed in outpatient clinics; and time to treatment. RESULTS: A total
      of 249 cancers were diagnosed in the index year. Sixty five (26.1%) were referred
      to two week standard clinics, 40 (16.1%) to routine colorectal surgical
      outpatient clinics, 54 (22%) to other clinics, and 88 (35.3%) were emergencies.
      Thirteen patients per week were referred to the two week standard clinics and 85%
      (54/65) of cancers so referred were seen within two weeks. The diagnostic yield
      of cancer in the two week standard clinic was 9.4% (65/695) compared with 2.2%
      (40/1815) in the routine colorectal surgical outpatient clinic (p<0.0001). Eighty
      five per cent of patients with cancer referred to outpatients matched the
      guidelines for the two week standard clinics. Only 46% of this group were so
      referred. Overall, delay to treatment and Dukes' stage were not improved in
      patients diagnosed in the two week standard clinics. CONCLUSIONS: Most patients
      with bowel cancer were not referred on the basis of the two week standard
      although most fulfilled the referral criteria, which had higher diagnostic
      yields. The two week standard clinics did not shorten the overall time to
      treatment or improve the stage of disease because the time lags before referral
      and after the outpatient appointment are the major causes of delay in the bowel
      cancer patient's journey.

PMID- 14960523
TI  - Severe hepatic injury in interleukin 18 (IL-18) transgenic mice: a key role for
      IL-18 in regulating hepatocyte apoptosis in vivo.
AB  - BACKGROUND: Interleukin 18 (IL-18) is a cytokine with pleiotropic activity that
      augments T helper 1 responses and cytotoxic activity of natural killer cells.
      METHODS: To assess the function of IL-18 in vivo, we generated IL-18 transgenic
      (IL-18 Tg) mice under the control of a CD2 promoter/enhancer construct. RESULTS:
      Macroscopically, IL-18 Tg mice showed reduced relative liver weight compared with
      wild-type littermates. TUNEL assays demonstrated increased hepatocyte apoptosis,
      and primary hepatocytes isolated from IL-18 Tg mice exhibited an increased
      spontaneous apoptosis rate. Furthermore, cross linking of Fas increased
      significantly the apoptosis rate in hepatocytes isolated from wild- type mice but
      to a much lesser extent in IL-18 Tg mice, suggesting spontaneous activation of
      the Fas pathway in the latter mice. In fact, in vivo blockade of Fas signal
      transduction by an adenovirus overexpressing the dominant negative form of the
      Fas associated death domain rescued hepatocytes from undergoing apoptosis.
      Finally, adoptive transfer of CD4(+) T cells from IL-18 Tg mice but not from wild
      type littermates in SCID mice resulted in severe liver failure with massive
      periportal fibrosis due to hepatocyte apoptosis. CONCLUSION: IL-18 plays a
      fundamental role in regulating hepatocyte apoptosis. Furthermore, our transgenic
      model provides a novel tool to study the mechanisms of IL-18 dependent liver
      injury in vivo.

PMID- 14960524
TI  - Improved characterisation of histologically proven liver tumours by contrast
      enhanced ultrasonography during the portal venous and specific late phase of SHU
      508A.
AB  - PURPOSE: Ultrasound is reported to be relatively unreliable in the
      characterisation of liver tumours. The purpose of this study was to assess the
      ability of contrast enhanced phase inversion ultrasound (PIUS), a new highly
      sensitive contrast specific technique, performed during the liver specific phase
      of Levovist, to differentiate between benign and malignant lesions of the liver.
      PATIENTS AND METHODS: A total of 174 patients with histologically proven liver
      tumours were prospectively examined with conventional B mode ultrasound and two
      minutes after intravenous bolus injection of SHU 508A (Levovist). The examination
      technique comprised: Siemens Sonoline Elegra, phase inversion harmonic imaging
      (ECI); high mechanical index (1.2-1.7) using a delayed two minute post contrast
      scanning technique. RESULTS: In all patients with malignant disease, hypoechoic
      contrast enhancement was seen during the portal venous phase, and convincing but
      variably less demarcated in 13 patients with hepatocellular carcinoma compared
      with all patients with liver metastases. The liver tumours proved to be
      histologically benign in 95 patients and malignant in 79 patients. Homogenous
      contrast enhancement with a mainly isoechogenic appearance in the portal venous
      and liver specific late phase was seen in almost all patients with benign liver
      lesions with the exception of one patient with an inflammatory pseudotumour of
      the liver and five patients with abscesses. These six exceptions all demonstrated
      a hypoechoic appearance in the portal venous and liver specific late phase.
      DISCUSSION: The ability of unenhanced ultrasonography to characterise liver
      disease is known to be limited. PIUS performed during the portal venous and liver
      specific late phase of Levovist may differentiate between benign and malignant
      liver tumours in most cases, with the exception of, for example, abscesses,
      scars, necrosis, cysts, and calcifications, which need to be excluded clinically
      and by conventional B mode ultrasonography.

PMID- 14960525
TI  - Steatosis affects chronic hepatitis C progression in a genotype specific way.
AB  - BACKGROUND AND AIMS: Liver steatosis is frequent in chronic hepatitis C,
      particularly in patients infected with hepatitis C virus (HCV) genotype 3. The
      aim of this study was to determine the relationship between steatosis and
      fibrosis in chronic hepatitis C as a function of viral genotype. METHODS: A
      multivariable logistic regression analysis was carried out in 755 chronic
      hepatitis C patients (mean body mass index (BMI) 24.11 kg/m(2); 178 with genotype
      3), consecutively admitted to three referral hospitals. Liver histology showed
      steatosis in 315 and fibrosis in 605 patients, of whom 187 had cirrhosis (78
      compensated and 109 decompensated). RESULTS: Steatosis was independently
      associated with fibrosis (p<0.001), genotype 3 (p<0.001), BMI (p<0.001), ongoing
      alcohol abuse (p<0.001), and age (p = 0.001). Fibrosis was associated with the
      Metavir activity score (p<0.001), age (p<0.001), steatosis (p = 0.001), past
      alcohol abuse for >5 years (p = 0.015), and BMI (p = 0.034). When regression
      analysis was repeated on patients divided according to viral genotype (that is, 3
      v non-3) to identify type specific risk factors, steatosis was associated with
      ongoing alcohol abuse (p<0.001) and age (p = 0.01) only in non-3 genotype
      infected patients and with Metavir activity (p = 0.044) only in genotype 3
      infected patients. Similarly, fibrosis was associated with steatosis only in
      genotype 3 infected individuals (p = 0.018), and with past alcohol abuse (p =
      0.003) and (marginally) diabetes (p = 0.078) only in non-3 genotype infected
      patients. CONCLUSIONS: Steatosis influences chronic hepatitis C progression in a
      genotype specific way. Patients infected with genotype 3 and histologically
      confirmed steatosis should not be deferred from effective antiviral therapy.

PMID- 14960526
TI  - Modest weight loss and physical activity in overweight patients with chronic
      liver disease results in sustained improvements in alanine aminotransferase,
      fasting insulin, and quality of life.
AB  - BACKGROUND AND AIM: Obesity is a risk factor for progression of fibrosis in
      chronic liver diseases such as non-alcoholic fatty liver disease and hepatitis C.
      The aim of this study was to investigate the longer term effect of weight loss on
      liver biochemistry, serum insulin levels, and quality of life in overweight
      patients with liver disease and the effect of subsequent weight maintenance or
      regain. PATIENTS: Thirty one patients completed a 15 month diet and exercise
      intervention. RESULTS: On completion of the intervention, 21 patients (68%) had
      achieved and maintained weight loss with a mean reduction of 9.4 (4.0)% body
      weight. Improvements in serum alanine aminotransferase (ALT) levels were
      correlated with the amount of weight loss (r = 0.35, p = 0.04). In patients who
      maintained weight loss, mean ALT levels at 15 months remained significantly lower
      than values at enrollment (p = 0.004), while in regainers (n = 10), mean ALT
      levels at 15 months were no different to values at enrollment (p = 0.79).
      Improvements in fasting serum insulin levels were also correlated with weight
      loss (r = 0.46, p = 0.04), and subsequent weight maintenance sustained this
      improvement. Quality of life was significantly improved after weight loss. Weight
      maintainers sustained recommended levels of physical activity and had higher
      fasting insulin levels (p = 0.03) at enrollment than weight regainers.
      CONCLUSION: In summary, these findings demonstrate that maintenance of weight
      loss and exercise in overweight patients with liver disease results in a
      sustained improvement in liver enzymes, serum insulin levels, and quality of
      life. Treatment of overweight patients should form an important component of the
      management of those with chronic liver disease.

PMID- 14960527
TI  - Effect of antiviral treatment on evolution of liver steatosis in patients with
      chronic hepatitis C: indirect evidence of a role of hepatitis C virus genotype 3
      in steatosis.
AB  - BACKGROUND AND AIM: Recent studies suggest that liver steatosis in chronic
      hepatitis C may be the expression of a direct cytopathic effect of hepatitis C
      virus (HCV), particularly in patients infected with genotype 3. To investigate
      this hypothesis, we studied the relationship between steatosis evolution and HCV
      clearance after antiviral treatment in patients with chronic hepatitis C and
      paired liver biopsies. METHODS: A total of 151 patients (37 with HCV genotype 3;
      114 with HCV non-3 genotypes) were selected according to the following criteria:
      presence of steatosis at initial biopsy; no antiviral treatment prior to the
      first biopsy; antiviral treatment received between the two biopsies; body mass
      index (BMI) <28 kg/m(2); absence of excessive alcohol intake; no serum hepatitis
      B surface antigen or human immunodeficiency virus antibodies; and absence of
      diabetes mellitus. Evolution of steatosis was examined by comparing steatosis
      grades between the two biopsies. RESULTS: Twenty five patients (16.5%) were
      sustained virological responders (SVR) to antiviral treatment. Steatosis
      evolution after antiviral treatment was as follows: improvement in 36% of cases;
      stability in 51%; and worsening in 13%. Steatosis improvement was significantly
      more frequent in SVR than in non-responders (NR) (64% v 31%; p<0.004). This
      significant difference occurred in patients infected with genotype 3 (91% v 19%;
      p<0.0001) but not in those infected with non-3 genotypes (43% v 34%; NS). Among
      the 25 SVR, improvement in steatosis was significantly more frequent in patients
      infected with genotype 3 than in those infected with non-3 genotypes (91% v 43%;
      p<0.04) whereas in NR, improvement in steatosis did not differ between those
      infected with genotype 3 and non-3 genotypes (19% v 34%; NS). In multivariate
      analysis, four factors were independently associated with steatosis improvement:
      sustained virological response to antiviral therapy (odds ratio (OR) 6.06 (95%
      confidence interval (CI) 1.61-22.9); p = 0.01), severe steatosis (OR 5.50 (95% CI
      1.54-19.6); p = 0.01), HCV genotype 3 (OR 2.90 (95% CI 0.85-10.0); p = 0.07), and
      BMI >25 kg/m(2) (OR 0.24 (95% CI 0.08-0.73); p = 0.02). CONCLUSIONS: Our results
      showed significant improvement in steatosis in patients infected with HCV
      genotype 3, who achieved sustained viral clearance. This provides further
      evidence for direct involvement of HCV genotype 3 in the pathogenesis of hepatic
      steatosis.

PMID- 14960528
TI  - Benefit of interferon therapy in hepatocellular carcinoma prevention for
      individual patients with chronic hepatitis C.
AB  - BACKGROUND: An increase in the incidence of hepatocellular carcinoma (HCC) in
      Japan since the 1980s suggests an imminent outbreak in other countries where
      viral spread occurred more recently. Interferon therapy for chronic hepatitis C,
      in general, has been shown to prevent HCC. AIMS: To determine the scale of
      benefit in individual patients. SUBJECTS: Histologically proven chronic hepatitis
      C patients in the Inhibition of Hepatocarcinogenesis by Interferon Therapy (IHIT)
      cohort (Ann Intern Med 1999;131:174), as updated in March 2003. METHODS: The
      lifetime risk for HCC was calculated based on HCC incidence rates, stratified by
      sex, age, fibrosis stage, and outcome of interferon therapy. The gain in HCC free
      survival was defined as the difference between expected HCC free survival with
      sustained virological response and that without. RESULTS: The gain in HCC free
      survival was greater when a patient was younger and fibrosis was more advanced.
      For example, a 30 year old male with F3 fibrosis gained 12.4 years by attaining
      sustained response while a patient with F1 fibrosis older than 60 years gained
      less than one year. For a treatment protocol with a given sustained response
      rate, prior estimation of the gain can be obtained by multiplying the calculated
      HCC free survival for responders by the response rate. CONCLUSIONS: The gain in
      HCC free survival may serve as an indicator of the benefit of interferon therapy
      in terms of HCC prevention and be useful in the consideration of indication and
      selection of treatment protocol for individual patients.

PMID- 14960530
TI  - Randomised controlled trial of long term portographic follow up versus variceal
      band ligation following transjugular intrahepatic portosystemic stent shunt for
      preventing oesophageal variceal rebleeding.
AB  - BACKGROUND/AIMS: Transjugular intrahepatic portosystemic stent shunt (TIPSS) is
      effective in the prevention of variceal rebleeding but requires invasive
      portographic follow up. This randomised controlled trial aims to test the
      hypothesis that combining variceal band ligation (VBL) with TIPSS can obviate the
      need for long term TIPSS surveillance without compromising clinical efficacy, and
      can reduce the incidence of hepatic encephalopathy. PATIENTS/METHODS: Patients
      who required TIPSS for the prevention of oesophageal variceal rebleeding were
      randomised to either TIPSS alone (n = 39, group 1) or TIPSS plus VBL (n = 40,
      group 2). In group 1, patients underwent long term TIPSS angiographic
      surveillance. In group 2, patients entered a banding programme with TIPSS
      surveillance only continued for up to one year. RESULTS: There was a tendency to
      higher variceal rebleeding in group 2 although this did not reach statistical
      significance (8% v 15%; relative hazard 0.58; 95% confidence interval (CI) 0.15
      2.33; p = 0.440). Mortality (47% v 40%; relative hazard 1.31; 95% CI 0.66-2.61; p
      = 0.434) was similar in the two groups. Hepatic encephalopathy was significantly
      less in group 2 (20% v 39%; relative hazard 2.63; 95% CI 1.11-6.25; p = 0.023).
      Hepatic encephalopathy was not statistically different after correcting for sex
      and portal pressure gradient (p = 0.136). CONCLUSIONS: TIPSS plus VBL without
      long term surveillance is effective in preventing oesophageal variceal
      rebleeding, and has the potential for low rates of encephalopathy. Therefore, VBL
      with short term TIPSS surveillance is a suitable alternative to long term TIPSS
      surveillance in the prevention of oesophageal variceal rebleeding.

PMID- 14960531
TI  - Hepatic fibrogenesis requires sympathetic neurotransmitters.
AB  - BACKGROUND AND AIMS: Hepatic stellate cells (HSC) are activated by liver injury
      to become proliferative fibrogenic myofibroblasts. This process may be regulated
      by the sympathetic nervous system (SNS) but the mechanisms involved are unclear.
      METHODS: We studied cultured HSC and intact mice with liver injury to test the
      hypothesis that HSC respond to and produce SNS neurotransmitters to promote
      fibrogenesis. RESULTS: HSC expressed adrenoceptors, catecholamine biosynthetic
      enzymes, released norepinephrine (NE), and were growth inhibited by alpha- and
      beta-adrenoceptor antagonists. HSC from dopamine beta-hydroxylase deficient (Dbh(
      /-)) mice, which cannot make NE, grew poorly in culture and were rescued by NE.
      Inhibitor studies demonstrated that this effect was mediated via G protein
      coupled adrenoceptors, mitogen activated kinases, and phosphatidylinositol 3
      kinase. Injury related fibrogenic responses were inhibited in Dbh(-/-) mice, as
      evidenced by reduced hepatic accumulation of alpha-smooth muscle actin(+ve) HSC
      and decreased induction of transforming growth factor beta1 (TGF-beta1) and
      collagen. Treatment with isoprenaline rescued HSC activation. HSC were also
      reduced in leptin deficient ob/ob mice which have reduced NE levels and are
      resistant to hepatic fibrosis. Treating ob/ob mice with NE induced HSC
      proliferation, upregulated hepatic TGF-beta1 and collagen, and increased liver
      fibrosis. CONCLUSIONS: HSC are hepatic neuroglia that produce and respond to SNS
      neurotransmitters to promote hepatic fibrosis.

PMID- 14960532
TI  - SLC11A1 promoter gene polymorphisms and fibrosis progression in chronic hepatitis
      C.
AB  - BACKGROUND AND AIMS: The solute carrier family 11 member 1 (SLC11A1) gene
      (formerly Nramp1) encodes for the protein solute carrier family 11, member 1. It
      affects susceptibility and clinical outcome of autoimmune and infectious
      diseases. We investigated the possible role of the functional polymorphism
      located in the promoter region of SLC11A1 and tumour necrosis factor (TNF) genes
      in the progression of fibrosis in chronic hepatitis C. METHODS: A total of 242
      Caucasian Spanish patients with biopsy proven chronic hepatitis C and 194 healthy
      control subjects were genotyped for SLC11A1 and TNF promoter polymorphisms.
      RESULTS: No significant differences in the distribution of frequencies among
      patient and control groups were observed. The SCL11A1 homozygous 2/2 genotype was
      rarely detected among patients showing advanced fibrosis (2/82; 2.4%) but was
      highly represented in those with mild fibrosis (29/160; 18.1%; odds ratio (OR)
      8.85 (95% confidence interval (CI) 1.9-55.2, p(c) = 0.002). In patients carrying
      allele 3 of SLC11A1, the presence of -238 TNF A/G was associated with advanced
      fibrosis (14/26 (53.8%) v 68/216 (31.4%); OR 2.53 (95% CI 1.03-6.23); p = 0.02).
      CONCLUSIONS: SLC11A1 gene promoter polymorphism could influence fibrosis
      progression in chronic hepatitis C in that the homozygous genotype 2/2 exerts a
      protective effect against cirrhosis development. Also, the combination of TNF 
      238 A/G and the presence of allele 3 is conducive to progression to pre-cirrhotic
      or cirrhotic stages of the disease.

PMID- 14960533
TI  - Progression of hepatic fibrosis in patients with hepatitis C: a prospective
      repeat liver biopsy study.
AB  - BACKGROUND: The natural history of hepatitis C virus (HCV) infection remains
      uncertain. Previous data concerning rates of progression are from studies using
      estimated dates of infection and single liver biopsy scores. We prospectively
      studied the rate of progression of fibrosis in HCV infected patients by repeat
      liver biopsies without intervening treatment. PATIENTS: We studied 214 HCV
      infected patients (126 male; median age 36 years (range 5-8)) with predominantly
      mild liver disease who were prospectively followed without treatment and assessed
      for risk factors for progression of liver disease. Interbiopsy interval was a
      median of 2.5 years. Paired biopsies from the same patient were scored by the
      same pathologist. RESULTS: Seventy of 219 (33%) patients showed progression of at
      least 1 fibrosis point in the Ishak score; 23 progressed at least 2 points.
      Independent predictors of progression were age at first biopsy and any fibrosis
      on first biopsy. Factors not associated with progression were: necroinflammation,
      duration of infection, alcohol consumption, alanine aminotransferase levels,
      current or past hepatitis B virus infection, ferritin, HCV genotype, and
      steatosis or iron deposition in the initial biopsy. CONCLUSIONS: One third of
      patients with predominantly mild hepatitis C showed significant fibrosis
      progression over a median period of 30 months. Histologically, mild hepatitis C
      is a progressive disease. The overall rate of fibrosis progression in patients
      with hepatitis C was low but increased in patients who were older or had fibrosis
      on their index biopsy. These data suggest that HCV infection will place an
      increasing burden on health care services in the next 20 years.

PMID- 14960534
TI  - Modulating the intestinal immune system: the role of lymphotoxin and GALT organs.
AB  - The gut associated immune system fences off potentially harmful intestinal
      antigens from the systemic circulation and induces systemic tolerance against
      luminal antigens. Intestinal immune responses against luminal antigens include
      IgA secretion and induction of regulatory cells. Unlike few other cytokines,
      lymphotoxin alpha/beta regulates the development of intestinal lymphoid organs.
      The embryonic development of Peyer's patches, postnatal lamina propria B cell
      development, and isolated lymphoid follicle development all depend on lymphotoxin
      beta receptor interactions. Lymphotoxin alpha/beta signalling also contributes to
      the development of mesenteric lymph nodes. In addition, intestinal inflammation
      is suppressed by inhibition of lymphotoxin beta signalling, an observation which
      has initiated clinical studies using this treatment principal. Intestinal
      follicular lymphoid organs are sites of antigen presentation. Antigen presenting
      cells tune the delicate balance between intestinal immune tolerance and
      inflammation. Therefore, gut associated lymphatic organs and factors regulating
      their development are critical for the prevention of adverse immune reactions to
      intestinal antigens. This review provides an overview on the role of lymphotoxin
      and the gut associated lymphatic organs in the regulation of oral tolerance and
      intestinal inflammation.

PMID- 14960536
TI  - Role of multi-detector row CT angiography in the management of gastric fundal
      varices.

PMID- 14960537
TI  - Primary antiphospholipid syndrome as a new cause of autoimmune pancreatitis.

PMID- 14960538
TI  - Treatment of interferon non-responsive chronic hepatitis C with triple therapy
      with interferon, ribavirin, and amantidine can be encouraging.

PMID- 14960539
TI  - The diagnostic dilemmas in discrimination between pancreatic carcinoma and
      chronic pancreatitis.

PMID- 14960540
TI  - Who should perform endoscopic procedures?

PMID- 14960541
TI  - Submucosal "dissection" in collagenous colitis.

PMID- 14960542
TI  - Responses to endothelin-1 in patients with advanced cirrhosis before and after
      liver transplantation.

PMID- 14960543
TI  - Small bowel malignancy in coeliac disease.

PMID- 14960544
TI  - Germline testing of mismatch repair genes is not aided by prescreening tumours
      for allelic loss.

PMID- 14960545
TI  - Late development of cholangiocarcinoma after hepaticojejunostomy due to ampullary
      carcinoma.

PMID- 14960546
TI  - Mild respiratory distress after wireless capsule endoscopy.

PMID- 14960547
TI  - Adoptive transfer of genetic susceptibility to Crohn's disease.

PMID- 14960549
TI  - How many kinds of visceral afferents?
AB  - Most afferent signals from the viscera do not give rise to conscious experience
      and yet they participate in the complex neural control of visceral functions.
      Surprisingly little information is available on the origin, morphology, and
      receptor functional characteristics of the nerve endings of most primary afferent
      neurones to the digestive tract. This review deals with the morphological nature
      of the afferent neurones that supply the gastrointestinal tract specifically.

PMID- 14960550
TI  - What activates visceral afferents?
AB  - Vagal and spinal afferents represent the information superhighways that convey
      sensory information from the gut to the central nervous system. These afferents
      are sensitive to both mechanical and chemical stimuli. Vagal afferents terminate
      in the muscle layers and in the mucosa. Muscle afferents are activated at
      physiological levels of distension and during peristalsis. In contrast, spinal
      afferents encode supraphysiological levels of intestinal pressure. Vagal and
      spinal afferents also express a wide range of membrane receptors to a variety of
      chemical mediators generated from both within and outside the gut wall. Some of
      these receptors are part of a modality specific transduction pathway involved in
      sensory signalling from the gut lumen to vagal afferent endings in the mucosa.
      Others, which are activated by substances derived from multiple cellular sources
      during ischaemia, injury, or inflammation act in a synergistic way to cause acute
      or chronic sensitisation of the afferent nerves to mechanical and chemical
      stimuli. Understanding the mechanisms that underlie hypersensitivity may have
      implications for the pharmaceutical approach to the treatment of functional bowel
      disorders like irritable bowel syndrome.

PMID- 14960551
TI  - Recent advances in understanding molecular mechanisms of primary afferent
      activation.
AB  - Thermal, mechanical, and chemical stimuli depolarise specialised damage sensing
      neurons to initiate electrical signals that may ultimately result in a sensation
      of pain. Over the past decade many of the receptors that transduce these signals
      have been identified by molecular cloning. In the absence of specific blockers,
      null mutant mice have proved valuable in exploring the function of these
      specialised receptors. As well as the mechanisms of signal transduction, the
      setting of thresholds for excitation and the transmission of electrical signals
      have also been the focus of intense interest. In vitro studies of dorsal root
      ganglion sensory neurons have thus facilitated rapid advances in our
      understanding of the biology of nociceptors. However, the specific properties of
      visceral afferents are poorly defined, and useful animal models of visceral pain
      are only now being developed. Visceral neuron receptor subtypes and the
      consequences of their activation in terms of pain perception and behaviour are
      thus subjects that still demand a major research effort.

PMID- 14960552
TI  - Sensitisation of gastrointestinal tract afferents.
AB  - Sensory innervation of the viscera serves a number of important functions,
      including regulation of visceral motility and secretory activity, and
      transmission of visceral sensations, including pain. There are many ways in which
      the sensitivity of visceral sensory neurones might be modulated, and these are
      discussed. Altered sensory neurone responsiveness may contribute to
      pathophysiological states such as irritable bowel syndrome, and the mechanisms
      leading to sensory neurone sensitisation offer novel targets for the treatment of
      such disorders.

PMID- 14960553
TI  - Interface between the intestinal environment and the nervous system.
AB  - Possible mechanisms by which the intestinal contents may influence afferent nerve
      fibres in the lamina propria of the intestinal mucosa are discussed in this brief
      review. After addressing intestinal epithelial permeability, endocrine and brush
      cells are discussed, as well as enterocytes, as sensors for luminal microbes.

PMID- 14960554
TI  - Putative therapeutic targets in the treatment of visceral hyperalgesia.
AB  - The management of abdominal pain remains a major challenge for clinicians despite
      an explosion of knowledge regarding the physiology and pathophysiology of sensory
      neural circuits. Initial progress was made in the field of somatic pain and this
      provided broad hypotheses that could be tested in the field of visceral pain. The
      major advances in our understanding of basic mechanisms underlying visceral pain
      originated in the urinary tract and have been applied to the gut. As yet, this
      increased understanding of enteric sensory physiology has yet to generate new
      effective treatments for abdominal pain. This review addresses novel insights
      into peripheral mechanisms underlying visceral hyperalgesia and their
      applicability to the development of novel therapeutic approaches to the treatment
      of chronic abdominal pain.

PMID- 14960556
TI  - Odorant specificity of single olfactory bulb neurons to amino acids in the
      channel catfish.
AB  - Odorant specificity to l-alpha-amino acids was determined for 245 olfactory bulb
      (OB) neurons recorded from 121 channel catfish. The initial tests included 4
      amino acids representing acidic [monosodium glutamate (Glu)], basic [arginine
      (Arg)], and neutral [possessing short: alanine (Ala) and long: methionine (Met)
      side chains] amino acids that were previously indicated to bind to independent
      olfactory receptor sites. Ninety-one (37%) units (Group I) tested at 1, 10, and
      100 microM showed high selectivity and were excited by only one of the 4 amino
      acids. Odorant specificity for the vast majority of Group I units did not change
      over the 3 s of response time analyzed. A total of 154 OB units (63%) (Group II)
      were excited by a second amino acid, but only at >/=10x odorant concentration. An
      additional 69 Group I units were tested with related amino acids and derivatives
      from 10(-9) to 10(-5) M to determine their excitatory odorant thresholds and
      selectivities. Two groups of units originally selective for Met were evident:
      those most sensitive to neutral amino acids having branched and linear side
      chains, respectively. OB units originally selective for Ala responded at low
      concentration to other similar amino acids. Units originally selective for Arg
      were excited at low concentration by amino acids possessing in their side chains
      at least 3 methylene groups and a terminal amide or guanidinium group. The
      specificities of the OB units determined electrophysiologically are sufficient to
      account for many of the previous results of behavioral discrimination of amino
      acids in this and related species.

PMID- 14960557
TI  - Opposing electrophysiological actions of 5-HT on noncholinergic and cholinergic
      neurons in the rat ventral pallidum in vitro.
AB  - The ventral pallidum in rat is a basal forebrain structure that contains neurons
      that project in the limbic striatopallidal circuitry and magnocellular
      cholinergic corticopetal neurons. Because 5-hydroxytryptamine (5-HT) terminals on
      dorsal raphe projections form close appositions with these neurons, we made patch
      clamp recordings in immature rat brain slices to determine whether they are
      modulated by postsynaptic 5-HT receptors. Inward currents were predominantly
      induced by 5-HT in noncholinergic neurons, which were distinguished from
      cholinergic neurons by immunohistochemical and electrophysiological criteria. The
      inward current induced by 5-HT was mimicked and occluded when adenylyl cyclase
      was stimulated with forskolin, and was almost abolished when h-currents in
      noncholinergic neurons were blocked with cesium. Consistent with 5-HT(7) receptor
      activation of h-curents by cAMP in other brain regions, we found inward currents
      were mimicked by the mixed 5-HT(1)/5-HT(7) agonists 5-methoxytryptamine, and by 5
      carboxamidotryptamine (5-CT), which was more potent than 5-HT. In contrast, 5
      HT(1) preferring 8-OH-DPAT was a weak partial agonist, and the 5-HT(1)-selective
      antagonist pindolol had no effect. However, despite this profile, antagonists
      that bind at the 5-HT(7) receptor only partly reduced the agonist inward current
      (SB-269970 and clozapine), or had no effect (mianserin and pimozide). We found in
      cholinergic neurons that 5-HT predominantly induced hyperpolarizing currents,
      which were carried by potassium channels, and were smaller than currents induced
      by 8-OH-DPAT and 5-CT. We conclude from this study that ascending 5-HT
      projections from the dorsal raphe could have direct and opposite effects on the
      activities of neurons within the limbic striatopallidal and cholinergic
      corticopetal circuitry in the ventral pallidum.

PMID- 14960558
TI  - Integration of retinal disparity and fixation-distance related signals toward an
      egocentric coding of distance in the posterior parietal cortex of primates.
AB  - For those movements that are directed toward objects located in extrapersonal
      space, it is necessary that visual inputs are first remapped from a retinal
      coordinate system to a body-centered one. The posterior parietal cortex (PPC)
      most likely integrates retinal and extraretinal information to determine the
      egocentric distance of an object located in three-dimensional (3-D) space. This
      determination requires both a retinal disparity signal and a parallel estimate of
      the fixation distance. We recorded from the lateral intraparietal area (LIP) to
      see if single neurons respond to both vergence angle and retinal disparity and if
      these two signals are integrated to encode egocentric distance. Monkeys were
      trained to make saccades to real targets in 3-D space. When both fixation
      distance and disparity of visual stimuli were varied, the disparity tuning of
      individual neurons display a fixation-distance modulation. We propose that the
      observed modulation contributes to a spatial coding domain intermediate between
      retinal and egocentric because the disparity tuning shifts in a systematic way
      with changes in fixation distance.

PMID- 14960559
TI  - Visual cortex neurons of monkeys and cats: temporal dynamics of the spatial
      frequency response function.
AB  - We measured the responses of striate cortex neurons as a function of spatial
      frequency on a fine time scale, over the course of an interval that is comparable
      to the duration of a single fixation (200 ms). Stationary gratings were flashed
      on for 200 ms and then off for 300 ms; the responses were analyzed at sequential
      1-ms intervals. We found that 1) the preferred spatial frequency shifts through
      time from low frequencies to high frequencies, 2) the latency of the response
      increases as a function of spatial frequency, and 3) the poststimulus time
      histograms (PSTHs) are relatively shape-invariant across spatial frequency. The
      dynamic shifts in preferred spatial frequency appear to be a simple consequence
      of the latency shifts and the transient nature of the PSTH. The effects of these
      dynamic shifts on the coding of spatial frequency information are examined within
      the context of several different temporal integration strategies, and pattern
      detection performance is determined as a function of the interval of integration,
      following response onset. The findings are considered within the context of
      related investigations as well as a number of functional issues: motion
      selectivity in depth, "coarse-to-fine" processing, direction selectivity, latency
      as a code for stimulus attributes, and behavioral response latency. Finally, we
      demonstrate that the results are qualitatively consistent with a simple
      feedforward model, similar to the one originally proposed in 1962 by Hubel and
      Wiesel, that incorporates measured differences in the response latencies and the
      receptive field sizes of different lateral geniculate nucleus inputs.

PMID- 14960560
TI  - Retinal pH reflects retinal energy metabolism in the day and night.
AB  - The extracellular pH of living tissue in the retina and elsewhere in the brain is
      lower than the pH of the surrounding milieu. We have shown that the pH gradient
      between the in vitro retina and the superfusion solution is regulated by a
      circadian (24-h) clock so that it is smaller in the subjective day than in the
      subjective night. We show here that the circadian changes in retinal pH result
      from a clock-mediated change in the generation of H+ that accompanies energy
      production. To demonstrate this, we suppressed energy metabolism and recorded the
      resultant reduction in the pH difference between the retina and superfusate. The
      magnitude of the reduction in the pH gradient correlated with the extent of
      energy metabolism suppression. We also examined whether the circadian-induced
      increase in acid production during the subjective night results from an increase
      in energy metabolism or from the selective activation of glycolysis compared with
      oxidative phosphorylation. We found that the selective suppression of either
      oxidative phosphorylation or glycolysis had almost identical effects on the
      dynamics and extent of H+ production during the subjective day and night. Thus
      the proportion of glycolysis and oxidative phosphorylation is maintained the same
      regardless of circadian time, and the pH difference between the tissue and
      superfusion solution can therefore be used to evaluate total energy production.
      We conclude that circadian clock regulation of retinal pH reflects circadian
      regulation of retinal energy metabolism.

PMID- 14960561
TI  - Dynamics of olfactory bulb input and output activity during odor stimulation in
      zebrafish.
AB  - The processing of odor-evoked activity in the olfactory bulb (OB) of zebrafish
      was studied by extracellular single unit recordings from the input and output
      neurons, i.e., olfactory receptor neurons (ORNs) and mitral cells (MCs),
      respectively. A panel of 16 natural amino acid odors was used as stimuli.
      Responses of MCs, but not ORNs, changed profoundly during the first few hundred
      milliseconds after response onset. In MCs, but not ORNs, the total evoked
      excitatory activity in the population was initially odor-dependent but
      subsequently converged to a common level. Hence, the overall population activity
      is regulated by network interactions in the OB. The tuning widths of both ORN and
      MC response profiles were similar and, on average, stable over time. However,
      when analyzed for individual neurons, MC response profiles could sharpen
      (excitatory response to fewer odors) or broaden (excitatory response to more
      odors), whereas ORN response profiles remained nearly unchanged. Several
      observations indicate that dynamic inhibition plays an important role in this
      remodeling. Finally, the reliability of odor identification based on MC
      population activity patterns improved over time, whereas odor identification
      based on ORN activity patterns was most reliable early in the odor response.
      These results demonstrate that several properties of MC, but not ORN, activity
      change during the initial phase of the odor response with important consequences
      for odor-encoding activity patterns. Furthermore, our data indicate that
      inhibitory interactions in the OB are important in dynamically shaping the
      activity of OB output neurons.

PMID- 14960562
TI  - Predictive smooth ocular pursuit during the transient disappearance of a visual
      target.
AB  - When a moving target disappears and there is a complete absence of visual
      feedback signals, eye velocity decays rapidly but often recovers to previous
      levels if there is an expectation the target will reappear further along its
      trajectory Given that eye velocity cannot be maintained under such circumstances,
      the anticipatory recovery may function to minimize the developing velocity error.
      When there is a change in target velocity during a transient, any recovery should
      ideally be scaled and hence predictive of the expected target velocity at
      reappearance. This study confirmed that subjects did not maintain eye velocity
      close to target velocity for the duration of the inter-stimulus interval (ISI).
      The majority of subjects exhibited an initial reduction in eye velocity followed
      by a scaled recovery prior to target reappearance. Eye velocity during the ISI
      was, therefore, predictive of the expected change in target velocity. These
      behavioral data were simulated using a model in which gain applied to the
      visuomotor drive is reduced after the loss of visual feedback and then modulated
      depending on subject's expectation regarding the target's future trajectory.

PMID- 14960563
TI  - Mitral and tufted cells differ in the decoding manner of odor maps in the rat
      olfactory bulb.
AB  - Mitral and tufted cells in the mammalian olfactory bulb are principal neurons,
      each type having distinct projection pattern of their dendrites and axons. The
      morphological difference suggests that mitral and tufted cells are functionally
      distinct and may process different aspects of olfactory information. To examine
      this possibility, we recorded odorant-evoked spike responses from mitral and
      middle tufted cells in the aliphatic acid- and aldehyde-responsive cluster at the
      dorsomedial part of the rat olfactory bulb. Homologous series of aliphatic acids
      and aldehydes were used for odorant stimulation. In response to adequate
      odorants, mitral cells showed spike responses with relatively low firing rates,
      whereas middle tufted cells responded with higher firing rates. Examination of
      the molecular receptive range (MRR) indicated that most mitral cells exhibited a
      robust inhibitory MRR, whereas a majority of middle tufted cells showed no or
      only a weak inhibitory MRR. In addition, structurally different odorants that
      activated neighboring clusters inhibited the spike activity of mitral cells,
      whereas they caused no or only a weak inhibition in the middle tufted cells.
      Furthermore, responses of mitral cells to an adequate excitatory odorant were
      greatly inhibited by mixing the odorant with other odorants that activated
      neighboring glomeruli. In contrast, odorants that activated neighboring glomeruli
      did not significantly inhibit the responses of middle tufted cells to the
      adequate excitatory odorant. These results indicate a clear difference between
      mitral and middle tufted cells in the manner of decoding the glomerular odor
      maps.

PMID- 14960564
TI  - Multiple domains of the co-chaperone Hop are important for Hsp70 binding.
AB  - The Hop/Sti1 co-chaperone binds to both Hsp70 and Hsp90. Biochemical and co
      crystallographic studies have suggested that the EEVD-containing C terminus of
      Hsp70 or Hsp90 binds specifically to one of the Hop tetratricopeptide repeat
      domains, TPR1 or TPR2a, respectively. Mutational analyses of Hsp70 and Hop were
      undertaken to better characterize interactions between the C terminus of Hsp70
      and Hop domains. Surprisingly, truncation of EEVD plus as many as 34 additional
      amino acids from the Hsp70 C terminus did not reduce the ability of Hsp70 mutants
      to co-immunoprecipitate with Hop, although further truncation eliminated Hop
      binding. Hop point mutations targeting a carboxylate clamp position in TPR1
      disrupted Hsp70 binding, as was expected; however, similar point mutations in
      TPR2a or TPR2b also inhibited Hsp70 binding in some settings. Using a yeast-based
      in vivo assay for Hop function, wild type Hop and TPR2b mutants could fully
      complement deletion of Sti1p; TPR1 and TPR2a point mutants could partially
      restore activity. Conformations of Hop and Hop mutants were probed by limited
      proteolysis. The TPR1 mutant digested in a similar manner to wild type; however,
      TPR2a and TPR2b mutants each displayed greater resistance to chymotryptic
      digestion. All point mutants retained an ability to dimerize, and none appeared
      to be grossly misfolded. These results raise questions about current models for
      Hop/Hsp70 interaction.

PMID- 14960565
TI  - Optimizing the binding affinity of a carrier protein: a case study on the
      interaction between soluble ifnar2 and interferon beta.
AB  - Prolonging the circulatory half-life of low mass protein drugs can be achieved
      either by administration of a pro-drug or through co-injection with a carrier
      protein that will slowly release the active protein. The rate of release is
      concentration and affinity dependent. The optimal relationship between these two
      in prolonging the half-life of a pro-drug is the focus of this work. Interferon
      (IFN) beta is one of the most widely used protein drugs in the clinic. Here, we
      show that the circulatory half-life of IFNbeta can be significantly extended by
      co-administration with the extracellular domain of the IFN receptor ifnar2
      (ifnar2-EC). To investigate the concentration/affinity relation, a range of
      tighter binding ifnar2-EC mutants was designed that bind IFNbeta, but not
      IFNalpha2, up to 50-fold tighter compared with the wild-type ifnar2-EC. This
      increased affinity is related to a slower dissociation rate, whereas the
      association of IFNbeta with ifnar2-EC is already near optimum. Using the wild
      type and mutant receptors, we investigated their potential in occluding IFNbeta
      from circulation in a tissue culture assay, as well as in rats. To determine the
      potential of ifnar2-EC as a carrier protein, we co-administered a mixture of
      IFNbeta and ifnar2-EC to rats both intravenously and subcutaneously, and followed
      the blood plasma concentrations of IFNbeta over time. The tighter binding ifnar2
      EC mutant had a clear advantage in prolonging the half-life of IFNbeta in
      circulation, even when lower protein concentrations were administered. A
      numerical simulation of the in vivo data demonstrates that the optimal binding
      affinity of a carrier protein is around the concentration needed to obtain
      optimal activity of the ligand.

PMID- 14960566
TI  - CMP-N-acetylneuraminic acid synthetase from Escherichia coli K1 is a bifunctional
      enzyme: identification of minimal catalytic domain for synthetase activity and
      novel functional domain for platelet-activating factor acetylhydrolase activity.
AB  - Escherichia coli CMP-NeuAc synthetase (EC 2.7.7.43) catalyzes the synthesis of
      CMP-NeuAc from CTP and NeuAc, which is essential for the formation of capsule
      polysialylate for strain K1. Alignment of the amino acid sequence of E. coli CMP
      NeuAc synthetase with those from other bacterial species revealed that the
      conserved motifs were located in its N termini, whereas the C terminus appeared
      to be redundant. Based on this information, a series of deletions from the 3'-end
      of the CMPNeuAc synthetase coding region was constructed and expressed in E.
      coli. As a result, the catalytic domain required for CMP-NeuAc synthetase was
      found to be in the N-terminal half consisting of amino acids 1-229. Using the
      strategy of tertiary structure prediction based on the homologous search of the
      secondary structure, the C-terminal half was recognized as an alpha1-subunit of
      bovine brain platelet-activating factor acetylhydrolase isoform I. The
      biochemical analyses showed that the C-terminal half consisting of amino acids
      228-418 exhibited platelet-activating factor acetylhydrolase activity. The enzyme
      properties and substrate specificity were similar to that of bovine brain alpha1
      subunit. Although its physiological function is still unclear, it has been
      proposed that the alpha1-subunit-like domain of E. coli may be involved in the
      traversal of the blood-brain barrier.

PMID- 14960567
TI  - The metastasis suppressor NM23-H1 possesses 3'-5' exonuclease activity.
AB  - NM23-H1 belongs to a family of eight gene products in humans that have been
      implicated in cellular differentiation and development, as well as oncogenesis
      and tumor metastasis. We have defined NM23-H1 biochemically as a 3'-5'
      exonuclease by virtue of its ability in stoichiometric amounts to excise single
      nucleotides in a stepwise manner from the 3' terminus of DNA. The activity is
      dependent upon the presence of Mg(2+), is most pronounced with single-stranded
      substrates or mismatched bases at the 3' terminus of double-stranded substrates,
      and is inhibited by both ATP and the incorporation of cordycepin, a 2'
      deoxyadenosine analogue, into the 3'-terminal position. The 3'-5' exonuclease
      activity was assigned to NM23-H1 by virtue of: 1) precise coelution of enzymatic
      activity with wild-type and mutant forms of NM23-H1 protein during purification
      by hydroxylapatite and gel filtration column high performance liquid
      chromatography and 2) significantly diminished activity exhibited by purified
      recombinant mutant forms of the proteins. Lysine 12 appears to play an important
      role in the catalytic mechanism, as evidenced by the significant reduction in 3'
      5' exonuclease activity resulting from a Lys(12) to glutamine substitution within
      the protein. 3'-5' Exonucleases are believed to play an important role in DNA
      repair, a logical candidate function underlying the putative antimetastatic and
      oncogenic activities of NM23-H1.

PMID- 14960568
TI  - Thermodynamic studies of the mechanism of metal binding to the Escherichia coli
      zinc transporter YiiP.
AB  - Sequence homology of the Escherichia coli YiiP places it within the family of
      cation diffusion facilitators, a family of membrane transporters that play a
      central role in regulating cellular zinc homeostasis. Here we describe the first
      thermodynamic and mechanistic studies of metal binding to a cation diffusion
      facilitator. Isothermal titration calorimetric analyses of the purified YiiP and
      binding competitions among Zn(2+), Cd(2+), and Hg(2+) revealed a mutually
      competitive binding site common to three metal ions and a set of noncompetitive
      binding sites, including one Cd(2+) site, one Hg(2+) site, and at least one
      Zn(2+) site, to which the binding of Zn(2+) exhibited partial inhibitions of both
      Cd(2+) and Hg(2+) bindings. Lowering the pH from 7.0 to 5.5 inhibited binding of
      Zn(2+) and Cd(2+) to the common site. Further, the enthalpy change of the Cd(2+)
      binding to the common site was found to be related linearly to the ionization
      enthalpy of the pH buffer with a slope corresponding to the release of 1.23 H(+)
      for each Cd(2+) binding. These H(+) effects are consistent with a coupled
      deprotonation process upon binding of Zn(2+) and Cd(2+). Modification of
      histidine residues by diethyl pyrocarbonate specifically inhibited Zn(2+) binding
      to the common binding site, indicating that the mechanism of binding
      deprotonation coupling involves a histidine residue(s).

PMID- 14960569
TI  - A multiprotein trafficking complex composed of SAP97, CASK, Veli, and Mint1 is
      associated with inward rectifier Kir2 potassium channels.
AB  - Strong inward rectifier potassium (Kir2) channels are important in the control of
      cell excitability, and their functions are modulated by interactions with
      intracellular proteins. Here we identified a complex of scaffolding/trafficking
      proteins in brain that associate with Kir2.1, Kir2.2, and Kir2.3 channels. By
      using a combination of affinity interaction pulldown assays and co
      immunoprecipitations from brain and transfected cells, we demonstrated that a
      complex composed of SAP97, CASK, Veli, and Mint1 associates with Kir2 channels
      via the C-terminal PDZ-binding motif. We further demonstrated by using in vitro
      protein interaction assays that SAP97, Veli-1, or Veli-3 binds directly to the
      Kir2.2 C terminus and recruits CASK. Co-immunoprecipitations indicated that
      specific Veli isoforms participate in forming distinct protein complexes in
      brain, where Veli-1 stably associates with CASK and SAP97, Veli-2 associates with
      CASK and Mint1, and Veli-3 associates with CASK, SAP97, and Mint1. Additionally,
      immunocytochemistry of rat cerebellum revealed overlapping expression of Kir2.2,
      SAP97, CASK, Mint1, with Veli-1 in the granule cell layer and Veli-3 in the
      molecular layer. We propose a model whereby Kir2.2 associates with distinct SAP97
      CASK-Veli-Mint1 complexes. In one complex, SAP97 interacts directly with the Kir2
      channels and recruits CASK, Veli, and Mint1. Alternatively, Veli-1 or Veli-3
      interacts directly with the Kir2 channels and recruits CASK and SAP97;
      association of Mint1 with the complex requires Veli-3. Expression of Kir2.2 in
      polarized epithelial cells resulted in targeting of the channels to the
      basolateral membrane and co-localization with SAP97 and CASK, whereas a dominant
      interfering form of CASK caused the channels to mislocalize. Therefore, CASK
      appears to be a central protein of a macromolecular complex that participates in
      trafficking and plasma membrane localization of Kir2 channels.

PMID- 14960570
TI  - The FlgS/FlgR two-component signal transduction system regulates the fla regulon
      in Campylobacter jejuni.
AB  - The human pathogen Campylobacter jejuni is a highly motile organism that carries
      a flagellum on each pole. The flagellar motility is regarded as an important
      trait in C. jejuni colonization of the intestinal tract, however, the knowledge
      of the regulation of this important colonization factor is rudimentary. We
      demonstrate by phosphorylation assays that the sensor FlgS and the response
      regulator FlgR form a two-component system that is on the top of the
      Campylobacter flagellum hierarchy. Phosphorylated FlgR is needed to activate RpoN
      dependent genes of which the products form the hook-basal body filament complex.
      By real-time reverse transcriptase-PCR we identified that FlgS, FlgR, RpoN, and
      FliA belong to the early flagellar genes and are regulated by sigma70. FliD and
      the putative anti-sigma-factor FlgM are regulated by a sigma54- and sigma28
      dependent promoters. Activation of the fla regulon is growth phase-dependent, a
      100-fold rpoN mRNA reduction is seen in the early stationary phase compared with
      the early logarithmic phase. Whereas flaB transcription decreases, flaA
      transcription increases in early stationary phase. Our data show that the C.
      jejuni flagellar hierarchy largely differs from that of other bacteria.
      Phenotypical analysis revealed that unflagellated C. jejuni mutants grow three
      times faster in broth medium compared with wild-type bacteria. In vivo the C.
      jejuni flagella are needed to pass the gastrointestinal tract of chickens, but
      not to colonize the ceaca of the chicken.

PMID- 14960571
TI  - Mechanical compression of cartilage explants induces multiple time-dependent gene
      expression patterns and involves intracellular calcium and cyclic AMP.
AB  - Chondrocytes are influenced by mechanical forces to remodel cartilage
      extracellular matrix. Previous studies have demonstrated the effects of
      mechanical forces on changes in biosynthesis and mRNA levels of particular
      extracellular matrix molecules, and have identified certain signaling pathways
      that may be involved. However, the broad extent and kinetics of mechano
      regulation of gene transcription has not been studied in depth. We applied static
      compressive strains to bovine cartilage explants for periods between 1 and 24 h
      and measured the response of 28 genes using real time PCR. Compression time
      courses were also performed in the presence of an intracellular calcium chelator
      or an inhibitor of cyclic AMP-activated protein kinase A. Cluster analysis of the
      data revealed four main expression patterns: two groups containing either
      transiently up-regulated or duration-enhanced expression profiles could each be
      subdivided into genes that did or did not require intracellular calcium release
      and cyclic AMP-activated protein kinase A for their mechano-regulation.
      Transcription levels for aggrecan, type II collagen, and link protein were up
      regulated approximately 2-3-fold during the first 8 h of 50% compression and
      subsequently down-regulated to levels below that of free-swelling controls by 24
      h. Transcription levels of matrix metalloproteinases-3, -9, and -13, aggrecanase
      1, and the matrix protease regulator cyclooxygenase-2 increased with the duration
      of 50% compression 2-16-fold by 24 h. Thus, transcription of proteins involved in
      matrix remodeling and catabolism dominated over anabolic matrix proteins as the
      duration of static compression increased. Immediate early genes c-fos and c-jun
      were dramatically up-regulated 6-30-fold, respectively, during the first 8 h of
      50% compression and remained up-regulated after 24 h.

PMID- 14960572
TI  - Pearson correlation analysis of microarray data allows for the identification of
      genetic targets for early B-cell factor.
AB  - B lymphocyte development is a complex biological process critically dependent on
      the transcription factor early B cell factor (EBF). To deepen understanding of
      the roles for EBF in this process, we have used Pearson correlation analysis to
      evaluate microarray data from a set of mouse B lymphoid cell lines representing
      different stages of development. Comparing the expression pattern of EBF to that
      of the other genes in the data set revealed that VpreB1, mb-1, and lambda5, all
      known target genes, presented high correlation values to EBF. High correlations
      were also seen for the VpreB3 and CD19 genes and biochemical as well as
      functional data supported that they are target genes for EBF even though the
      expression of CD19 was critically dependent of Pax-5. We also obtained evidence
      for extensive collaborative actions of EBF and E47 even though microarray
      analysis of hematopoetic progenitor cells ectopically expressing these proteins
      suggested that they activated only a subset of pre-B cell restricted genes.

PMID- 14960573
TI  - CCAAT enhancer-binding protein alpha is required for interleukin-6 receptor alpha
      signaling in newborn hepatocytes.
AB  - The acute phase response is an evolutionarily conserved response of the liver to
      inflammatory stimuli, which aids the body in host defense and homeostasis. We
      have previously reported that CCAAT enhancer-binding protein alpha (C/EBPalpha)
      is required for the induction of acute phase protein (APP) genes in newborn mice
      in response to lipopolysaccharide. In this paper, we describe a mechanism by
      which C/EBPalpha knock-out mice are unable to induce APP gene expression in
      response to inflammatory stimuli. We demonstrate that the lack of acute phase
      response in C/EBPalpha knock-out mice is because of a hepatocyte autonomous
      defect. C/EBPalpha knock-out hepatocytes do not activate STAT3 in response to
      recombinant interleukin (IL)-6, indicating a defect in the IL-6 pathway.
      C/EBPalpha knock-out hepatocytes also do not show activation of other IL-6
      receptor (IL-6R)-mediated Janus kinase substrates, gp130, SHP-2, and Tyk2.
      Further examination of the IL-6 pathway demonstrated that C/EBPalpha knock-out
      hepatocytes have decreased IL-6Ralpha protein levels caused, in part, by reduced
      protein stability. However, other components of the IL-6 pathway are intact, as
      demonstrated by rescue of STAT3 activation and APP gene induction with
      recombinant-soluble IL-6R linked to IL-6 cytokine (Hyper-IL-6) or with another
      gp130 signaling cytokine, Oncostatin M. In conclusion, C/EBPalpha is required for
      the proper regulation of IL-6Ralpha protein in hepatocytes resulting in a lack of
      acute phase protein gene induction in newborn C/EBPalpha null mice in response to
      lipopolysaccharide or cytokines.

PMID- 14960574
TI  - PimF, a mannosyltransferase of mycobacteria, is involved in the biosynthesis of
      phosphatidylinositol mannosides and lipoarabinomannan.
AB  - Phosphatidylinositol mannosides (PIMs) and their related molecules lipomannan
      (LM) and lipoarabinomannan (LAM) are important components of the mycobacterial
      cell wall. These molecules mediate host-pathogen interactions and exhibit
      immunomodulatory activities. The biosynthesis of these lipoglycans is not fully
      understood. In this study, we have identified a mycobacterial gene (Rv1500) that
      is involved in the synthesis of PIMs. We have named this gene pimF. Transposon
      mutagenesis of pimF of Mycobacterium marinum resulted in multiple phenotypes,
      including altered colony morphology, disappearance of tetracyl-PIM(7), and
      accumulation of tetraacyl-PIM(5). The syntheses of LAM and LM were also affected.
      In addition, the pimF mutant exhibited a defect during infection of cultured
      macrophage cells. Although the mutant was able to replicate and persist within
      macrophages, the initial cell entry step was inefficient. Transformation of the
      M. marinum mutant with the pimF homolog of Mycobacterium tuberculosis
      complemented all of the above mentioned phenotypes. These results provide
      evidence that PimF is a mannosyltransferase. However, sequence analysis indicates
      that PimF is distinct from mannosyltransferases involved in the early steps of
      PIM synthesis. PimF catalyzes the formation of high molecular weight PIMs, which
      are precursors for the synthesis of LAM and LM. As such, this work marks the
      first analysis of a mannosyltransferase involved in the later stages of PIM
      synthesis.

PMID- 14960575
TI  - Signaling through the leukocyte integrin LFA-1 in T cells induces a transient
      activation of Rac-1 that is regulated by Vav and PI3K/Akt-1.
AB  - Integrin LFA-1 is a receptor that is able to transmit multiple intracellular
      signals in leukocytes. Herein we show that LFA-1 induces a potent and transient
      increase in the activity of the small GTPase Rac-1 in T cells. Maximal Rac-1
      activity peaked 10-15 min after LFA-1 stimulation and rapidly declined to basal
      levels at longer times. We have identified Vav, a guanine nucleotide exchange
      factor for Rac-1, and PI3K/Akt, as regulators of the activation and inactivation
      phases of the activity of Rac-1, respectively, in the context of LFA-1 signaling
      based on the following experimental evidence: (i) LFA-1 induced activation of Vav
      and PI3K/Akt with kinetics consistent with a regulatory role for these molecules
      on Rac-1, (ii) overexpression of a constitutively active Vav mutant induces
      activation of Rac independently of LFA-1 stimulation whereas overexpression of a
      dominant-negative Vav mutant blocks LFA-1-mediated Rac activation, (iii)
      pharmacological inhibition of PI3K/Akt prevented the fall in the activity of Rac
      1 after its initial activation but had no effect on Vav activity, and (iv)
      overexpression of a dominant-negative or a constitutively active Akt-1 induced or
      inhibited, respectively, Rac-1 activity. Finally, we show that T cells with a
      sustained Rac activity have impaired capacity to elongate onto ICAM-1. These
      results demonstrate that down-regulation of the activity of this GTPase is a
      requirement for the regulation of T cell morphology and motility and highlight
      the importance of temporal regulation of the signaling triggered from this
      integrin.

PMID- 14960576
TI  - Smac/DIABLO selectively reduces the levels of c-IAP1 and c-IAP2 but not that of
      XIAP and livin in HeLa cells.
AB  - The inhibitor of apoptosis (IAP) proteins bind and inhibit caspases via their
      baculovirus IAP repeat domains. Some of these IAPs are capable of ubiquitinating
      themselves and their interacting proteins through the ubiquitin-protein
      isopeptide ligase activity of their RING domain. The Drosophila IAP antagonists
      Reaper, Hid, and Grim can accelerate the degradation of Drosophila IAP1 and some
      mammalian IAPs by promoting their ubiquitin-protein isopeptide ligase activity.
      Here we show that Smac/DIABLO, a mammalian functional homolog of Reaper/Hid/Grim,
      selectively causes the rapid degradation of c-IAP1 and c-IAP2 but not XIAP and
      Livin in HeLa cells, although it efficiently promotes the auto-ubiquitination of
      them all. Smac binding to c-IAP via its N-terminal IAP-binding motif is the
      prerequisite for this effect, which is further supported by the findings that
      Smac N-terminal peptide is sufficient to enhance c-IAP1 ubiquitination, and Smac
      no longer promotes the ubiquitination of mutant c-IAP1 lacking all three
      baculovirus IAP repeat domains. In addition, different IAPs require the same
      ubiquitin-conjugating enzymes UbcH5a and UbcH6 for their ubiquitination. Taken
      together, Smac may serve as a key molecule in vivo to selectively reduce the
      protein level of c-IAPs through the ubiquitin/proteasome pathway.

PMID- 14960577
TI  - Identification of critical residues of choline kinase A2 from Caenorhabditis
      elegans.
AB  - Choline kinase catalyzes the phosphorylation of choline by ATP, the first
      committed step in the CDP-choline pathway for phosphatidylcholine biosynthesis.
      To begin to elucidate the mechanism of catalysis by this enzyme, choline kinase A
      2 from Caenorhabditis elegans was analyzed by systematic mutagenesis of highly
      conserved residues followed by analysis of kinetic and structural parameters.
      Specifically, mutants were analyzed with respect to K(m) and k(cat) values for
      each substrate and Mg(2+), inhibitory constants for Mg(2+) and Ca(2+), secondary
      structure as monitored by circular dichroism, and sensitivity to unfolding in
      guanidinium hydrochloride. The most severe impairment of catalysis occurred with
      the modification of Asp-255 and Asn-260, which are located in the conserved
      Brenner's phosphotransferase motif, and Asp-301 and Glu-303, in the signature
      choline kinase motif. For example, mutation of Asp-255 or Asp-301 to Ala
      eliminated detectable catalytic activity, and mutation of Asn-260 and Glu-303 to
      Ala decreased k(cat) by 300- and 10-fold, respectively. Additionally, the K(m)
      for Mg(2+) for mutants N260A and E303A was approximately 30-fold higher than that
      of wild type. Several other residues (Ser-86, Arg-111, Glu-125, and Trp-387) were
      identified as being important: Catalytic efficiencies (k(cat)/K(m)) for the
      enzymes in which these residues were mutated to Ala were reduced to 2-25% of wild
      type. The high degree of structural similarity among choline kinase A-2,
      aminoglycoside phosphotransferases, and protein kinases, together with the
      results from this mutational analysis, indicates it is likely that these
      conserved residues are located at the catalytic core of choline kinase.

PMID- 14960578
TI  - Integrins in mechanotransduction.
AB  - Mechanical forces are crucial to the regulation of cell and tissue morphology and
      function. At the cellular level, forces influence cytoskeletal organization, gene
      expression, proliferation, and survival. Integrin-mediated adhesions are
      intrinsically mechanosensitive and a large body of data implicates integrins in
      sensing mechanical forces. We review the relationship between integrins and
      mechanical forces, the role of integrins in cellular responses to stretch and
      fluid flow, and propose that some of these events are mechanistically related.

PMID- 14960579
TI  - Activation of intrinsic and extrinsic proapoptotic signaling pathways in
      interleukin-18-mediated human cardiac endothelial cell death.
AB  - Endothelial cells are the primary targets of circulating immune and inflammatory
      mediators. We hypothesize that interleukin-18, a proinflammatory cytokine,
      induces endothelial cell apoptosis. Human cardiac microvascular endothelial cells
      (HCMEC) were treated with interleukin (IL) 18. mRNA expression was analyzed by
      ribonuclease protection assay, protein levels by immunoblotting, and cell death
      by enzyme-linked immunosorbent assay and fluorescence-activated cell sorter
      analysis. We also investigated the signal transduction pathways involved in IL-18
      mediated cell death. Treatment of HCMEC with IL-18 increases 1) NF-kappaB DNA
      binding activity; 2) induces kappaB-driven luciferase activity; 3) induces IL
      1beta and TNF-alpha expression via NF-kappaB activation; 4) inhibits
      antiapoptotic Bcl-2 and Bcl-X(L); 5) up-regulates proapoptotic Fas, Fas-L, and
      Bcl-X(S) expression; 6) induces fas and Fas-L promoter activities via NF-kappaB
      activation; 7) activates caspases-8, -3, -9, and BID; 8) induces cytochrome c
      release into the cytoplasm; 9) inhibits FLIP; and 10) induces HCME cell death by
      apoptosis as seen by increased annexin V staining and increased levels of mono-
      and oligonucleosomal fragmented DNA. Whereas overexpression of Bcl-2
      significantly attenuated IL-18-induced endothelial cell apoptosis, Bcl-2/Bcl-X(L)
      chimeric phosphorothioated 2'-MOE-modified antisense oligonucleotides potentiated
      the proapoptotic effects of IL-18. Furthermore, caspase-8, IKK-alpha, and NF
      kappaB p65 knockdown or dominant negative IkappaB-alpha and dominant negative
      IkappaB-beta or kinase dead IKK-beta significantly attenuated IL-18-induced HCME
      cell death. Effects of IL-18 on cell death are direct and are not mediated by
      intermediaries such as IL-1beta, tumor necrosis factor-alpha, or interferon
      gamma. Taken together, our results indicate that IL-18 activates both intrinsic
      and extrinsic proapoptotic signaling pathways, induces endothelial cell death,
      and thereby may play a role in myocardial inflammation and injury.

PMID- 14960580
TI  - Cell volume regulation in response to hypotonicity is impaired in HeLa cells
      expressing a protein kinase Calpha mutant lacking kinase activity.
AB  - The chloride conductance (G(Cl,swell)) that participates in the regulatory volume
      decrease process triggered by osmotic swelling in HeLa cells was impaired by
      removal of extracellular Ca(2+), depletion of intracellular Ca(2+) stores with
      thapsigargin, or by preloading the cells with BAPTA-AM (1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid). Furthermore, overnight exposure
      to the phorbol ester tetradecanoyl phorbol acetate and acute incubation with
      inhibitors of the conventional protein kinase C (PKC) isoforms
      bisindolylmaleimide I and Go6976 inhibited G(Cl,swell). Treatment of HeLa cells
      with U73122, a phospholipase C inhibitor, also prevented G(Cl,swell).
      Hypotonicity induced selective PKC alpha accumulation in the
      membrane/cytoskeleton fraction in fractionation experiments and translocation of
      a green fluorescent protein-PKC alpha fusion protein to the plasma membrane of
      transiently transfected HeLa cells. To further explore the role of PKCs in
      hypotonicity-induced G(Cl,swell), HeLa clones stably expressing either a kinase
      dead dominant negative variant of the Ca(2+)-dependent PKC isoform alpha (PKC
      alpha K386R) or of the atypical PKC isoform zeta (PKCzeta K275W) were generated.
      G(Cl,swell) was significantly reduced in HeLa cells expressing the dominant
      negative PKC alpha mutant but remained unaltered in cells expressing dominant
      negative PKCzeta. These findings strongly implicate PKC alpha as a critical
      regulatory element that is required for efficient regulatory volume decrease in
      HeLa cells.

PMID- 14960581
TI  - Ricin triggers apoptotic morphological changes through caspase-3 cleavage of
      BAT3.
AB  - Ricin, one of type II ribosomal inactivating proteins, inhibits protein
      biosynthesis by its RNA N-glycosidase activity. By yeast two-hybrid screening,
      the human BAT3 (HLA-B-associated transcript 3) was isolated as a ricin A-chain
      interacting protein. A canonical caspase-3 cleavage site, DEQD(1001) was found at
      the C-terminal region of BAT3. Ricin induced the apoptosis by activating caspase
      3 and leading to the cleavage of BAT3 at 4 h after treatment while DNA laddering
      at 24 h. The cleavage is completely inhibited by zDEVD-fmk, a caspase-3 specific
      inhibitor. In addition, cleavage of BAT3 is blocked in caspase-3-deficient MCF-7
      cells, indicating that BAT3 is a novel caspase-3 substrate. Evidence indicates
      that caspase-3 activated by ricin acts on BAT3 at the caspase cleavage site,
      DEQD(1001) to release a C-terminal fragment designated CTF-131. The CTF-131
      induces phosphatidylserine exposure, cell rounding, and chromatin condensation as
      ricin does. Moreover, silencing expression of endogenous BAT3 concomitantly
      suppresses ricin-induced apoptosis. Together, our results suggest a model that
      ricin triggers morphological changes of apoptosis by caspase-3-mediated
      proteolytic activation of BAT3.

PMID- 14960582
TI  - Wnt activates the Tak1/Nemo-like kinase pathway.
AB  - Genetic studies on endoderm-mesoderm specification in Caenorhabditis elegans have
      demonstrated a role for several Wnt cascade components as well as for a MAPK-like
      pathway in this process. The latter pathway includes the MAPK kinase kinase-like
      MOM-4/Tak1, its adaptor TAP-1/Tab1, and the MAPK-like LIT-1/Nemo-like kinase. A
      model has been proposed in which the Tak1 kinase cascade counteracts the Wnt
      cascade at the level of beta-catenin/TCF phosphorylation. In this model, the
      signal that activates the Tak1 kinase cascade is unknown. As an alternative
      explanation of these genetic data, we have explored whether Tak1 is directly
      activated by Wnt. We find that Wnt1 stimulation results in autophosphorylation
      and activation of MOM-4/Tak1 in a TAP-1/Tab1-dependent fashion. Wnt1-induced Tak1
      stimulation activates Nemo-like kinase, resulting in the phosphorylation of TCF.
      Our results combined with the genetic data from C. elegans imply a mechanism
      whereby Wnt directly activates the MOM-4/Tak1 kinase signaling pathway. Thus, Wnt
      signal transduction through the canonical pathway activates beta-catenin/TCF,
      whereas Wnt signal transduction through the Tak1 pathway phosphorylates and
      inhibits TCF, which might function as a feedback mechanism.

PMID- 14960583
TI  - Translational induction of the inhibitor of apoptosis protein HIAP2 during
      endoplasmic reticulum stress attenuates cell death and is mediated via an
      inducible internal ribosome entry site element.
AB  - Prolonged endoplasmic reticulum (ER) stress leads to activation of caspases and
      cell death. The inhibitor of apoptosis (IAP) proteins are intrinsic inhibitors of
      apoptosis by virtue of inhibiting distinct caspases and are, therefore, critical
      regulators of cell death. Here we demonstrate that the expression of one member
      of the IAP family, HIAP2, is induced in response to ER stress and attenuates ER
      stress-induced cell death. The induction of HIAP2 is executed at the level of
      protein synthesis and is mediated by an inducible internal ribosome entry site
      (IRES) element. The triggering of ER stress results in caspase-mediated
      proteolytic processing of eukaryotic initiation factor p97/DAP5/NAT1, producing a
      fragment that specifically activates HIAP2 IRES. These data suggest an existence
      of a novel mechanism that regulates apoptotic response in ER stress.

PMID- 14960584
TI  - A functional interaction between the p75 neurotrophin receptor interacting
      factors, TRAF6 and NRIF.
AB  - Neurotrophin signaling through the p75 receptor regulates apoptosis within the
      nervous system both during development and in response to injury. Whereas a
      number of p75 interacting factors have been identified, how these upstream
      factors function in a coordinated manner to mediate receptor signaling is still
      unclear. Here, we report a functional interaction between TRAF6 and the
      neurotrophin receptor interacting factor (NRIF), two proteins known to associate
      with the intracellular domain of the p75 neurotrophin receptor. The association
      between NRIF and TRAF6 was direct and occurred with both endogenous and
      ectopically expressed proteins. A KRAB repressor domain of NRIF and the carboxyl
      terminal, receptor-binding region of TRAF6 were required for the interaction. Co
      expression of TRAF6 increased the levels of NRIF protein and induced its nuclear
      translocation. Reciprocally, NRIF enhanced TRAF6-mediated activation of the c-Jun
      NH2-terminal kinase (JNK) by 3-fold, while only modestly increasing the
      stimulation of NF-kappaB. The expression of both NRIF and TRAF6 was required for
      reconstituting p75 activation of JNK in HEK293 cells, whereas NRIF mutants
      lacking the TRAF6 interaction domain were unable to substitute for the full
      length protein in facilitating activation of the kinase. These results suggest
      that NRIF and TRAF6 functionally interact to facilitate neurotrophin signaling
      through the p75 receptor.

PMID- 14960585
TI  - A novel cyanobacterial SmtB/ArsR family repressor regulates the expression of a
      CPx-ATPase and a metallothionein in response to both Cu(I)/Ag(I) and
      Zn(II)/Cd(II).
AB  - A novel SmtB/ArsR family metalloregulator, denoted BxmR, has been identified and
      characterized from the cyanobacterium Oscillatoria brevis. Genetic and
      biochemical evidence reveals that BxmR represses the expression of both bxa1,
      encoding a CPx-ATPase metal transporter, as well as a divergently transcribed
      operon encoding bxmR and bmtA, a heavy metal sequestering metallothionein.
      Derepression of the expression of all three genes is mediated by both monovalent
      (Ag(I) and Cu(I)) and divalent (Zn(II) and Cd(II)) heavy metal ions, a novel
      property among SmtB/ArsR metal sensors. Electrophoretic gel mobility shift
      experiments reveal that apoBxmR forms multiple resolvable complexes with
      oligonucleotides containing a single 12-2-12 inverted repeat derived from one of
      the two operator/promoter regions with similar apparent affinities. Preincubation
      with either monovalent or divalent metal ions induces disassembly of both the
      BxmR-bxa1 and BxmR-bxmR/bmtA operator/promoter complexes. Interestingly, the
      temporal regulation of expression of bxa1 and bmtA mRNAs is different in O.
      brevis with bxa1 induced first upon heavy metal treatment, followed by bmtA/bxmR.
      A dynamic interplay among Bxa1, BmtA, and BxmR is proposed that maintains metal
      homeostasis in O. brevis by balancing the relative rates of metal storage and
      efflux of multiple heavy metal ions.

PMID- 14960586
TI  - Determination of the role of the human RNase H1 in the pharmacology of DNA-like
      antisense drugs.
AB  - Although ribonuclease H activity has long been implicated as a molecular
      mechanism by which DNA-like oligonucleotides induce degradation of target RNAs,
      definitive proof that one or more RNase H is responsible is lacking. To date, two
      RNase H enzymes (H1 and H2) have been cloned and shown to be expressed in human
      cells and tissues. To determine the role of RNase H1 in the mechanism of action
      of DNA-like antisense drugs, we varied the levels of the enzyme in human cells
      and mouse liver and determined the correlation of those levels with the effects
      of a number of DNA-like antisense drugs. Our results demonstrate that in human
      cells RNase H1 is responsible for most of the activity of DNA-like antisense
      drugs. Further, we show that there are several additional previously undescribed
      RNases H in human cells that may participate in the effects of DNA-like antisense
      oligonucleotides.

PMID- 14960587
TI  - Kinetic characterization of mutations found in propionic acidemia and
      methylcrotonylglycinuria: evidence for cooperativity in biotin carboxylase.
AB  - Acetyl-CoA carboxylase catalyzes the committed step in fatty acid synthesis in
      all plants, animals, and bacteria. The Escherichia coli form is a multifunctional
      enzyme consisting of three separate proteins: biotin carboxylase,
      carboxyltransferase, and the biotin carboxyl carrier protein. The biotin
      carboxylase component, which catalyzes the ATP-dependent carboxylation of biotin
      using bicarbonate as the carboxylate source, has a homologous functionally
      identical subunit in the mammalian biotin-dependent enzymes propionyl-CoA
      carboxylase and 3-methylcrotonyl-CoA carboxylase. In humans, mutations in either
      of these enzymes result in the metabolic deficiency propionic acidemia or
      methylcrotonylglycinuria. The lack of a system for structure-function studies of
      these two biotin-dependent carboxylases has prevented a detailed analysis of the
      disease-causing mutations. However, structural data are available for E. coli
      biotin carboxylase as is a system for its overexpression and purification. Thus,
      we have constructed three site-directed mutants of biotin carboxylase that are
      homologous to three missense mutations found in propionic acidemia or
      methylcrotonylglycinuria patients. The mutants M169K, R338Q, and R338S of E. coli
      biotin carboxylase were selected for study to mimic the disease-causing mutations
      M204K and R374Q of propionyl-CoA carboxylase and R385S of 3-methylcrotonyl-CoA
      carboxylase. These three mutants were subjected to a rigorous kinetic analysis to
      determine the function of the residues in the catalytic mechanism of biotin
      carboxylase as well as to establish a molecular basis for the two diseases. The
      results of the kinetic studies have revealed the first evidence for negative
      cooperativity with respect to bicarbonate and suggest that Arg-338 serves to
      orient the carboxyphosphate intermediate for optimal carboxylation of biotin.

PMID- 14960588
TI  - A Kruppel-like factor KLF15 contributes fasting-induced transcriptional
      activation of mitochondrial acetyl-CoA synthetase gene AceCS2.
AB  - Acetyl-CoA synthetase 2 (AceCS2) produces acetyl-CoA for oxidation through the
      citric acid cycle in the mitochondrial matrix. AceCS2 is highly expressed in the
      skeletal muscle and is robustly induced by fasting. Quantification of AceCS2
      transcripts both in C2C12 and human myotubes indicated that fasting-induced
      AceCS2 gene expression appears to be independent on insulin action.
      Characterization of 5'-flanking region of the mouse AceCS2 gene demonstrates that
      Kruppel-like factor 15 (KLF15) plays a key role in the trans-activation of the
      AceCS2 gene. Deletion and mutation analyses of AceCS2 promoter region revealed
      that the most proximal KLF site is a curtail site for the trans-activation of the
      AceCS2 gene by KLF15. Using Sp-null Drosophila SL2 cells, we showed that the
      combination of KLF15 and Sp1 resulted in a synergistic activation of the AceCS2
      promoter. Mutation analyses of three GC-boxes in the AceCS2 promoter indicated
      that the GC-box, located 8 bases downstream of the most proximal KLF15 site, is
      the most important GC-box in the synergistic trans-activation of the AceCS2 gene
      by KLF15 and Sp1. GST pull-down assays showed that KLF15 interacts with Sp1 in
      vitro. Quantification of various KLF transcripts revealed that 48 h fasting
      robustly induced the KLF15 transcripts in the skeletal muscle. Together with the
      trans-activation of the AceCS2 promoter, it is suggested that fasting-induced
      AceCS2 expression is largely contributed by KLF15. Furthermore, KLF15
      overexpression induced the levels of AceCS2 transcripts both in myoblasts and in
      myotubes, indicating that AceCS2 gene expression in vivo is indeed induced by
      KLF15.

PMID- 14960589
TI  - Function-blocking integrin alphavbeta6 monoclonal antibodies: distinct ligand
      mimetic and nonligand-mimetic classes.
AB  - We have generated a panel of potent, selective monoclonal antibodies that bind
      human and mouse alpha(v)beta(6) integrin with high affinity (up to 15 pm). A
      subset of these antibodies blocked the binding of alpha(v)beta(6) to the
      transforming growth factor-beta1 latency-associated peptide with IC(50) values as
      low as 18 pm, and prevented the subsequent alpha(v)beta(6)-mediated activation of
      transforming growth factor-beta1. The antibodies also inhibited alpha(v)beta(6)
      binding to fibronectin. The blocking antibodies form two biochemical classes. One
      class, exemplified by the ligand-mimetic antibody 6.8G6, bound to the integrin in
      a divalent cation-dependent manner, contained an RGD motif or a related sequence
      in CDR3 of the heavy chain, was blocked by RGD-containing peptides, and was
      internalized by alpha(v)beta(6)-expressing cells. Despite containing an RGD
      sequence, 6.8G6 was specific for alpha(v)beta(6) and showed no cross-reactivity
      with the RGD-binding integrins alpha(v)beta(3), alpha(v)beta(8),or
      alpha(IIb)beta(3). The nonligand-mimetic blocking antibodies, exemplified by
      6.3G9, were cation-independent, were not blocked by RGD-containing peptides, were
      not internalized, and did not contain RGD or related sequences. These two classes
      of antibody were unable to bind simultaneously to alpha(v)beta(6), suggesting
      that they may bind overlapping epitopes. The "ligand-mimetic" antibodies are the
      first to be described for alpha(v)beta(6) and resemble those described for
      alpha(IIb)beta(3). We also report for the first time the relative abilities of
      divalent cations to promote alpha(v)beta(6) binding to latency-associated peptide
      and to the ligand-mimetic antibodies. These antibodies should provide valuable
      tools to study the ligand-receptor interactions of alpha(v)beta(6) as well as the
      role of alpha(v)beta(6) in vivo.

PMID- 14960590
TI  - Hepatitis C virus suppresses the IRE1-XBP1 pathway of the unfolded protein
      response.
AB  - Hepatitis C virus (HCV) gene expression disrupts normal endoplasmic reticulum
      (ER) functions and induces ER stress. ER stress results from the accumulation of
      unfolded or misfolded proteins in the ER; cells can alleviate this stress by
      degrading or refolding these proteins. The IRE1-XBP1 pathway directs both protein
      refolding and degradation in response to ER stress. Like IRE1-XBP1, other
      branches of the ER stress response mediate protein refolding. However, IRE1-XBP1
      can also specifically activate protein degradation. We show here that XBP1
      expression is elevated in cells carrying HCV subgenomic replicons, but XBP1 trans
      activating activity is repressed. This prevents the IRE1-XBP1 transcriptional
      induction of EDEM (ER degradation-enhancing alpha-mannosidase-like protein). The
      mRNA expression of EDEM is required for the degradation of misfolded proteins.
      Consequently, misfolded proteins are stable in cells expressing HCV replicons.
      HCV may suppress the IRE1-XBP1 pathway to stimulate the synthesis of its viral
      proteins. IRE1alpha-null MEFs, a cell line with a defective IRE1-XBP1 pathway,
      show elevated levels of HCV IRES-mediated translation. Therefore, HCV may
      suppress the IRE1-XBP1 pathway to not only promote HCV expression but also to
      contribute to the persistence of the virus in infected hepatocytes.

PMID- 14960591
TI  - Acid-sensing ion channel 2 (ASIC2) modulates ASIC1 H+-activated currents in
      hippocampal neurons.
AB  - Hippocampal neurons express subunits of the acid-sensing ion channel (ASIC1 and
      ASIC2) and exhibit large cation currents that are transiently activated by acidic
      extracellular solutions. Earlier work indicated that ASIC1 contributed to the
      current in these neurons and suggested its importance for normal behavior.
      However, the specific contribution of ASIC1 and ASIC2 subunits to acid-evoked
      currents in hippocampal neurons remained uncertain. To decipher the individual
      role of the ASIC subunits, we studied H(+)-gated currents in neurons from both
      ASIC1 and ASIC2 null mice. We found that much of the current was produced by
      ASIC1a/2a heteromultimeric channels, and individual subunits made distinct
      contributions. The ASIC1a subunit was key in establishing current amplitude. The
      ASIC2a subunit had little effect on amplitude but influenced desensitization,
      recovery from desensitization, pH sensitivity, and the response to modulatory
      agents. We also found heterogeneity in the contribution of ASIC2 throughout the
      neuronal population, with individual neurons expressing both ASIC1a
      homomultimeric and ASIC1a/2a heteromultimeric channels. Studies of neurons
      heterozygous for disrupted ASIC alleles indicated that the properties of H(+)
      gated currents are dependent on the proportion of the individual subunits. These
      findings indicate that the absolute and relative amounts of ASIC subunits
      determine the amplitude and properties of hippocampal H(+)-gated currents and
      therefore may contribute to normal physiology and pathophysiology.

PMID- 14960592
TI  - On the transcriptional regulation of methicillin resistance: MecI repressor in
      complex with its operator.
AB  - Bacterial resistance to antibiotics poses a serious worldwide public health
      problem due to the high morbidity and mortality caused by infectious diseases.
      Most hospital-onset infections are associated with methicillin-resistant
      Staphylococcus aureus (MRSA) strains that have acquired multiple drug resistance
      to beta-lactam antibiotics. In a response to antimicrobial stress, nearly all
      clinical MRSA isolates produce beta-lactamase (BlaZ) and a penicillin-binding
      protein with low affinity for beta-lactam antibiotics (PBP2a, also known as PBP2'
      or MecA). Both effectors are regulated by homologous signal transduction systems
      consisting of a sensor/transducer and a transcriptional repressor. MecI
      (methicillin repressor) blocks mecA but also blaZ transcription and that of
      itself and the co-transcribed sensor/transducer. The structure of MecI in complex
      with a cognate operator double-stranded DNA reveals a homodimeric arrangement
      with a novel C-terminal spiral staircase dimerization domain responsible for
      dimer integrity. Each protomer interacts with the DNA major groove through a
      winged helix DNA-binding domain and specifically recognizes the nucleotide
      sequence 5'-Gua-Thy-Ade-X-Thy-3'. This results in an unusual convex bending of
      the DNA helix. The structure of this first molecular determinant of methicillin
      resistance in complex with its target DNA provides insights into its regulatory
      mechanism and paves the way for new antimicrobial strategies against MRSA.

PMID- 14960593
TI  - Identification of species-specific determinants of the action of the antagonist
      capsazepine and the agonist PPAHV on TRPV1.
AB  - The vanilloid receptor 1 (VR1 or TRPV1) ion channel is activated by noxious heat,
      low pH and by a variety of vanilloid-related compounds. The antagonist,
      capsazepine is more effective at inhibiting the human TRPV1 response to pH 5.5
      than the rat TRPV1 response to this stimulus. Mutation of rat TRPV1 at three
      positions in the S3 to S4 region, to the corresponding human amino acid residues
      I514M, V518L, and M547L decreased the IC(50) values for capsazepine inhibition of
      the pH 5.5 response from >10,000 nm to 924 +/- 241 nm in [Ca(2+)](i) assays and
      increased capsazepine inhibition of the capsaicin response to levels seen for
      human TRPV1. We have previously noted that phorbol 12-phenylacetate 13-acetate 20
      homovanillate (PPAHV) is a strong agonist of rat TRPV1 but not human TRPV1 in
      [Ca(2+)](i) assays (1). Mutation of methionine 547 in S4 of rat TRPV1 to leucine,
      found in human TRPV1 (M547L), reduced the ability of PPAHV to activate TRPV1 by
      approximately 20-fold. The reciprocal mutation of human TRPV1 (L547M) enabled the
      human receptor to respond to PPAHV. These mutations did not significantly affect
      the agonist activity of capsaicin, resiniferatoxin (RTX) or olvanil in
      [Ca(2+)](i) assays. Introducing the equivalent mutation into guinea pig TRPV1
      (L549M) increased the agonist potency of PPAHV by > 10-fold in the [Ca(2+)](i)
      assay and increased the amplitude of the evoked current. The rat M547L mutation
      reduced the affinity of RTX binding. Thus, amino acids within the S2-S4 region
      are important sites of agonist and antagonist interaction with TRPV1.

PMID- 14960594
TI  - Poly(ADP-ribose) polymerase-1-mediated cell death in astrocytes requires NAD+
      depletion and mitochondrial permeability transition.
AB  - Extensive activation of poly(ADP-ribose) polymerase-1 (PARP-1) by DNA damage is a
      major cause of caspase-independent cell death in ischemia and inflammation. Here
      we show that NAD(+) depletion and mitochondrial permeability transition (MPT) are
      sequential and necessary steps in PARP-1-mediated cell death. Cultured mouse
      astrocytes were treated with the cytotoxic concentrations of N-methyl-N'-nitro-N
      nitrosoguanidine or 3-morpholinosydnonimine to induce DNA damage and PARP-1
      activation. The resulting cell death was preceded by NAD(+) depletion,
      mitochondrial membrane depolarization, and MPT. Sub-micromolar concentrations of
      cyclosporin A blocked MPT and cell death, suggesting that MPT is a necessary step
      linking PARP-1 activation to cell death. In astrocytes, extracellular NAD(+) can
      raise intracellular NAD(+) concentrations. To determine whether NAD(+) depletion
      is necessary for PARP-1-induced MPT, NAD(+) was restored to near-normal levels
      after PARP-1 activation. Restoration of NAD(+) enabled the recovery of
      mitochondrial membrane potential and blocked both MPT and cell death.
      Furthermore, both cyclosporin A and NAD(+) blocked translocation of the apoptosis
      inducing factor from mitochondria to nuclei, a step previously shown necessary
      for PARP-1-induced cell death. These results suggest that NAD(+) depletion and
      MPT are necessary intermediary steps linking PARP-1 activation to AIF
      translocation and cell death.

PMID- 14960595
TI  - From structure and dynamics of protein L7/L12 to molecular switching in ribosome.
AB  - Based on the (1)H-(15)N NMR spectroscopy data, the three-dimensional structure
      and internal dynamic properties of ribosomal protein L7 from Escherichia coli
      were derived. The structure of L7 dimer in solution can be described as a set of
      three distinct domains, tumbling rather independently and linked via flexible
      hinge regions. The dimeric N-terminal domain (residues 1-32) consists of two
      antiparallel alpha-alpha-hairpins forming a symmetrical four-helical bundle,
      whereas the two identical C-terminal domains (residues 52-120) adopt a compact
      alpha/beta-fold. There is an indirect evidence of the existence of transitory
      helical structures at least in the first part (residues 33-43) of the hinge
      region. Combining structural data for the ribosomal protein L7/L12 from NMR
      spectroscopy and x-ray crystallography, it was suggested that its hinge region
      acts as a molecular switch, initiating "ratchet-like" motions of the L7/L12 stalk
      with respect to the ribosomal surface in response to elongation factor binding
      and GTP hydrolysis. This hypothesis allows an explanation of events observed
      during the translation cycle and provides useful insights into the role of
      protein L7/L12 in the functioning of the ribosome.

PMID- 14960596
TI  - Dopamine operates as a subsecond modulator of food seeking.
AB  - The dopamine projection to the nucleus accumbens has been implicated in behaviors
      directed toward the acquisition and consumption of natural rewards. The
      neurochemical studies that established this link made time-averaged measurements
      over minutes, and so the precise temporal relationship between dopamine changes
      and these behaviors is not known. To resolve this, we sampled dopamine every 100
      msec using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in the
      nucleus accumbens of rats trained to press a lever for sucrose. Cues that signal
      the opportunity to respond for sucrose evoked dopamine release (67 +/- 20 nm)
      with short latency (0.2 +/- 0.1 sec onset). When the same cues were presented to
      rats naive to the cue-sucrose pairing, similar dopamine signals were not
      observed. Thus, cue-evoked increases in dopamine in trained rats reflected a
      learned association between the cues and sucrose availability. Lever presses for
      sucrose occurred at the peak of the dopamine surges. After lever presses, and
      while sucrose was delivered and consumed, no further increases in dopamine were
      detected. Rather, dopamine returned to baseline levels. Together, the results
      strongly implicate subsecond dopamine signaling in the nucleus accumbens as a
      real-time modulator of food-seeking behavior.

PMID- 14960597
TI  - Rapid arrival and integration of ascending sensory information in layer 1
      nonpyramidal neurons and tuft dendrites of layer 5 pyramidal neurons of the
      neocortex.
AB  - Ascending sensory inputs arriving in layer 1 of the neocortex carry crucial
      signals for detecting salient information; but how the inputs are processed in
      layer 1 is unknown. Using a whole-cell in vivo recording technique targeting
      nonpyramidal neurons in layer 1 and tuft dendrites of layer 5 pyramidal neurons
      in layers 1-2, we examined the processing of these ascending sensory inputs in
      the barrel cortex. Here, we show that local circuit and deeper-layer-projecting
      neurons in layer 1, as well as tuft dendrites and somata of layer 5 pyramidal
      neurons, respond to multiple whiskers (6-15) with robust EPSPs. Remarkably, the
      latency for primary whisker-evoked responses is as short as approximately 5-7
      msec in layer 1 neurons and tuft dendrites of layer 5 pyramidal neurons. In
      addition, the latency for primary whisker-evoked responses in tuft dendrites of
      layer 5 pyramidal neurons is approximately 1 msec shorter than that in somata.
      These results indicate that ascending sensory inputs arrive in layers 1 and 4
      concurrently, which provides a neural mechanism for rapid integration and
      coincident detection of salient sensory information.

PMID- 14960598
TI  - Ectopic expression of the catalytic subunit of telomerase protects against brain
      injury resulting from ischemia and NMDA-induced neurotoxicity.
AB  - The catalytic subunit of telomerase reverse transcriptase (TERT) protects
      dividing cells from replicative senescence in vitro. Here, we show that
      expression of TERT mRNA is induced in the ipsilateral cortical neurons after
      occlusion of the middle cerebral artery in adult mice. Transgenic mice that
      overexpress TERT showed significant resistance to ischemic brain injury. Among
      excitotoxicity, oxidative stress, and apoptosis comprising of routes of ischemic
      neuronal death, NMDA receptor-mediated excitotoxicity was reduced in forebrain
      cell cultures overexpressing TERT. NMDA-induced accumulation of cytosolic free
      Ca2+ ([Ca2+]c) was reduced in forebrain neurons from TERT transgenic mice, which
      was attributable to the rapid flow of [Ca2+]c into the mitochondria from the
      cytosol without change in Ca2+ influx and efflux through the plasma membrane. The
      present study provides evidence that TERT is inducible in postmitotic neurons
      after ischemic brain injury and prevents NMDA neurotoxicity through shift of the
      cytosolic free Ca2+ into the mitochondria, and thus plays a protective role in
      ameliorating ischemic neuronal cell death.

PMID- 14960599
TI  - A role for prefrontal cortex in memory storage for trace fear conditioning.
AB  - The prefrontal cortex has been shown to participate in the association of events
      separated by time. However, it is not known whether the prefrontal cortex stores
      the memory for these relationships. Trace conditioning is a form of classical
      conditioning in which a time gap separates the conditioned stimulus (CS) from the
      unconditioned stimulus (US), the association of which has been shown to depend on
      prefrontal activity. Here we demonstrate that inhibition of extracellular signal
      regulated kinase (Erk) cascade (a biochemical pathway involved in long-term
      memory storage) in the rat medial prefrontal cortex did not interfere with memory
      encoding for trace fear conditioning but impaired memory retention. In addition,
      animals displayed impaired memory for the irrelevancy of the training context.
      Hippocampal Erk phosphorylation was found to have a later time course than
      prefrontal Erk phosphorylation after trace fear conditioning, indicating a direct
      role for the prefrontal cortex in associative memory storage for temporally
      separated events as well as in memory storage of relevancy.

PMID- 14960600
TI  - Circadian regulation of cGMP-gated channels of vertebrate cone photoreceptors:
      role of cAMP and Ras.
AB  - Circadian oscillators in chicken cone photoreceptors regulate the gating
      properties of cGMP-gated cationic channels (CNGCs) such that they have a higher
      apparent affinity for cGMP during the subjective night. Here we show that cAMP,
      acting through protein kinase A (PKA), Ras, and Erk, is part of the circadian
      output pathway controlling CNGCs. Endogenous and exogenous cAMP cause activation
      of Erk and Ras, which are more active at night in cones, and increase the
      apparent affinity of CNGCs for cGMP. The Ras farnesyl transferase inhibitor
      manumycin-A, and a dominant-negative form of Ras (RasN17) block the circadian
      rhythms in CNGC gating, as well as the effects of cAMP. A dominant-negative form
      of the MEK kinase B-Raf also blocks circadian and cAMP modulation of CNGCs. The
      circadian output pathway modulating CNGC channels is comprised in part of cAMP -
      > PKA --> Ras --> B-Raf --> MEK --> Erk --> --> CNGCs. cAMP activation of Ras and
      Erk occur within minutes, whereas modulation of CNGCs requires >1 hr. However,
      cAMP protagonists do not alter rhythms in cPer2 mRNA, and their effects on CNGCs
      cannot be attributed to clock phase-shifting.

PMID- 14960601
TI  - Selective activation of corticotropin-releasing factor-2 receptors on
      neurochemically identified neurons in the rat dorsal raphe nucleus reveals dual
      actions.
AB  - The dorsal raphe (DR)-serotonin (5-HT) system has been implicated in stress
      related psychiatric disorders. Stress may impact on this system through
      corticotropin-releasing factor (CRF), which densely innervates the DR. CRF binds
      to CRF-R1 and CRF-R2 receptors in the DR and has complex and opposing effects
      depending on the dose used and the endpoint examined. To clarify the impact of
      CRF on the DR-5-HT system, the effects of selectively activating CRF-R2 receptors
      (the predominant subtype) on extracellular DR neuronal activity were examined in
      halothane-anesthetized rats. Because the DR is neurochemically heterogeneous,
      when possible, neurons were labeled with neurobiotin for subsequent neurochemical
      classification as 5-HT or non-5-HT. Relatively low doses of urocortin II (UII)
      (0.1-10 ng) injected into the DR inhibited most (79%; n = 34) neurons, whereas a
      higher dose (30 ng) inhibited 28% and activated 41% (n = 29). An analysis of
      effects on neurochemically identified neurons revealed that 5-HT neurons were
      inhibited by 0.1-10 ng of UII and activated by 30 ng of UII. Activation of 5-HT
      neurons by 30 ng of UII likely resulted from disinhibition because the majority
      of non-5-HT neurons were inhibited by this dose. Antisauvagine-30, but not
      antalarmin, antagonized UII, implicating CRF-R2 receptors in the effects. The
      results suggest that activation of CRF-R2 on DR-5-HT neurons inhibits neuronal
      activity, whereas activation of CRF-R2 receptors on non-5-HT neurons may
      indirectly excite DR-5-HT neurons through disinhibition. Importantly, the tone of
      the DR-5-HT system can be regulated in a dynamic manner through CRF-R2
      activation, being either decreased or increased depending on the level of
      endogenous or exogenous ligand.

PMID- 14960602
TI  - A novel antipyretic action of 15-deoxy-Delta12,14-prostaglandin J2 in the rat
      brain.
AB  - Fever is an important part of the host defense response, yet fever can be
      detrimental if it is uncontrolled. We provide the first evidence that 15-deoxy
      Delta12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand for peroxisome
      proliferator-activated receptor gamma (PPARgamma), can attenuate the febrile
      response to lipopolysaccharide (LPS) in rats via an action on the brain.
      Furthermore, we show that PPARgamma is expressed in the hypothalamus, an
      important locus in the brain for fever generation. In addition, 15d-PGJ2 and its
      synthesizing enzyme (PGD2 synthase) were present in rat cerebrospinal fluid, and
      their levels were enhanced in response to systemic injection of LPS. The
      antipyretic effect of 15d-PGJ2 was associated with reduction in LPS-stimulated
      cyclooxygenase-2 expression in the hypothalamus but not in p44/p42 mitogen
      activated protein kinase phosphorylation or in the expression of the PPARgamma.
      Thus it is likely that there is a parallel induction of an endogenous prostanoid
      pathway in the brain capable of limiting deleterious actions of the
      proinflammatory prostaglandin E2-dependent pathway.

PMID- 14960603
TI  - Postsynaptic calcium influx at single synaptic contacts between pyramidal neurons
      and bitufted interneurons in layer 2/3 of rat neocortex is enhanced by
      backpropagating action potentials.
AB  - Pyramidal neurons in layer 2/3 (L2/3) of the rat somatosensory cortex excite
      somatostatin-positive inhibitory bitufted interneurons located in the same
      cortical layer via glutamatergic synapses. A rise in volume-averaged dendritic
      [Ca2+]i evoked by backpropagating action potentials (APs) reduces glutamatergic
      excitation via a retrograde signal, presumably dendritic GABA. To measure the
      rise in local [Ca2+]i at synaptic contacts during suprathreshold excitation, we
      identified single synaptic contacts in the acute slice preparation in pairs of
      pyramidal and bitufted cells each loaded with a Ca2+ indicator dye. Repetitive
      APs (10-15 APs at 50 Hz) evoked in a L2/3 pyramidal neuron gave rise to
      facilitating unitary EPSPs in the bitufted cell. Subthreshold EPSPs evoked a
      transient rise in [Ca2+]i of 80-250 nM peak amplitude at the postsynaptic
      dendritic site. The local postsynaptic [Ca2+]i transient was restricted to 10
      microm of dendritic length, lasted for 200 msec, and was mediated predominantly
      by NMDA receptor channels. When EPSPs were suprathreshold, the evoked AP
      backpropagated into the apical and basal dendritic arbor and increased the local
      [Ca2+]i transient at active contacts by approximately twofold, with a peak
      amplitude reaching 130-450 nM. This value is in the range of the half-maximal
      dendritic [Ca2+]i, evoking retrograde inhibition of glutamate release from
      boutons of pyramids. The localized enhancement of dendritic Ca2+ influx at
      synaptic contacts by synaptically evoked backpropagating APs could represent one
      mechanism by which a retrograde signal can limit the excitation of bitufted
      interneurons by L2/3 pyramids when these are repetitively active.

PMID- 14960604
TI  - Enteric dopaminergic neurons: definition, developmental lineage, and effects of
      extrinsic denervation.
AB  - The existence of enteric dopaminergic neurons has been suspected; however, the
      innervation of the gut by sympathetic nerves, in which dopamine (DA) is the
      norepinephrine precursor, complicates analyses of enteric DA. We now report that
      transcripts encoding tyrosine hydroxylase (TH) and the DA transporter (DAT) are
      present in the murine bowel (small intestine > stomach or colon; proximal colon >
      distal colon). Because sympathetic neurons are extrinsic, transcripts encoding TH
      and DAT in the bowel are probably derived from intrinsic neurons. TH protein was
      demonstrated immunocytochemically in neuronal perikarya (submucosal >> myenteric
      plexus; small intestine > stomach or colon). TH, DA, and DAT immunoreactivities
      were coincident in subsets of neurons (submucosal > myenteric) in guinea pig and
      mouse intestines in situ and in cultured guinea pig enteric ganglia. Surgical
      ablation of sympathetic nerves by extrinsic denervation of loops of the bowel did
      not affect DAT immunoreactivity but actually increased numbers of TH
      immunoreactive neurons, expression of mRNA encoding TH and DAT, and enteric DOPAC
      (the specific dopamine metabolite). The fetal gut contains transiently
      catecholaminergic (TC) cells. TC cells are the proliferating crest-derived
      precursors of mature neurons that are not catecholaminergic and, thus, disappear
      after embryonic day (E) 14 (mouse) or E15 (rat). TC cells appear early in
      ontogeny, and their development/survival is dependent on mash-1 gene expression.
      In contrast, the intrinsic TH-expressing neurons of the murine bowel appear late
      (perinatally) and are mash-1 independent. We conclude that the enteric nervous
      system contains intrinsic dopaminergic neurons that arise from a mash-1
      independent lineage of noncatecholaminergic precursors.

PMID- 14960605
TI  - Exacerbation of motor neuron disease by chronic stimulation of innate immunity in
      a mouse model of amyotrophic lateral sclerosis.
AB  - Innate immunity is a specific and organized immunological program engaged by
      peripheral organs and the CNS to maintain homeostasis after stress and injury. In
      neurodegenerative disorders, its putative deregulation, featured by inflammation
      and activation of glial cells resulting from inherited mutations or
      viral/bacterial infections, likely contributes to neuronal death. However, it
      remains unclear to what extent environmental factors and innate immunity
      cooperate to modulate the interactions between the neuronal and non-neuronal
      elements in the perturbed CNS. In the present study, we addressed the effects of
      acute and chronic administration of lipopolysaccharide (LPS), a Gram-negative
      bacterial wall component, in a genetic model of neurodegeneration. Transgenic
      mice expressing a mutant form of the superoxide dismutase 1 (SOD1(G37R)) linked
      to familial amyotrophic lateral sclerosis were challenged intraperitoneally with
      a single nontoxic or repeated injections of LPS (1 mg/kg). At different ages,
      SOD1(G37R) mice responded normally to acute endotoxemia. Remarkably, only a
      chronic challenge with LPS in presymptomatic 6-month-old SOD1(G37R) mice
      exacerbated disease progression by 3 weeks and motor axon degeneration. Closely
      associated with the severity of disease is the stronger and restricted
      upregulation of the receptor of innate immunity Toll-like receptor 2 and
      proinflammatory cytokines in degenerating regions of the ventral spinal cord and
      efferent fiber tracts of the brain from the LPS-treated SOD1(G37R) mice. This
      robust immune response was not accompanied by the establishment of acquired
      immunity. Our results provide solid evidence that environmental factors and
      innate immunity can cooperate to influence the course of disease of an inherited
      neuropathology.

PMID- 14960606
TI  - In vitro ischemic tolerance involves upregulation of glutamate transport partly
      mediated by the TACE/ADAM17-tumor necrosis factor-alpha pathway.
AB  - A short ischemic event [ischemic preconditioning (IPC)] can result in a
      subsequent resistance to severe ischemic injury (ischemic tolerance). Although
      tumor necrosis factor-alpha (TNF-alpha) contributes to the brain damage found
      after cerebral ischemia, its expression and neuroprotective role in models of IPC
      have also been described. Regarding the role of TNF-alpha convertase
      (TACE/ADAM17), we have recently shown its upregulation in rat brain after IPC
      induced by transient middle cerebral artery occlusion and that subsequent TNF
      alpha release accounts for at least part of the neuroprotection found in this
      model. We have now used an in vitro model of IPC using rat cortical cultures
      exposed to sublethal oxygen-glucose deprivation (OGD) to investigate TACE
      expression and activity after IPC and the subsequent mechanisms of ischemic
      tolerance. OGD-induced cell death was significantly reduced in cells exposed to
      IPC by sublethal OGD 24 hr before, an effect that was inhibited by the TACE
      inhibitor BB3103 (1 microm) and anti-TNF-alpha antibody (2 microg/ml) and that
      was mimicked by TNF-alpha (10 pg/ml) preincubation. Western blot analysis showed
      that TACE expression is increased after IPC. IPC caused TNF-alpha release, an
      effect that was blocked by the selective TACE inhibitor BB-3103. In addition, IPC
      diminished the increase in extracellular glutamate caused by OGD and increased
      cellular glutamate uptake and expression of EAAT2 and EAAT3 glutamate
      transporters; however, only EAAT3 upregulation was mediated by increased TNF
      alpha. These data demonstrate that neuroprotection induced by IPC involves
      upregulation of glutamate uptake partly mediated by TACE overexpression.

PMID- 14960607
TI  - Diversity of functional astroglial properties in the respiratory network.
AB  - A population of neurons in the caudal medulla generates the rhythmic activity
      underlying breathing movements. Although this neuronal network has attracted
      great attention for studying neuronal aspects of synaptic transmission, functions
      of glial cells supporting this neuronal activity remain unclear. To investigate
      the role of astrocytes in the respiratory network, we applied
      electrophysiological and immunohistochemical techniques to characterize
      astrocytes in regions involved in the generation and transmission of rhythmic
      activity. In the ventral respiratory group and the hypoglossal nucleus (XII) of
      acutely isolated brainstem slices, we analyzed fluorescently labeled astrocytes
      obtained from TgN(GFAP-EGFP) transgenic mice with the whole-cell voltage-clamp
      technique. Three subpopulations of astrocytes could be discerned by their
      distinct membrane current profiles. A first group of astrocytes was characterized
      by nonrectifying, symmetrical and voltage-independent potassium currents and a
      robust glutamate transporter response to d-aspartate. A second group of
      astrocytes showed additional A-type potassium currents, whereas a third group,
      identified by immunolabeling for the glial progenitor marker NG2, expressed
      outwardly rectifying potassium currents, smaller potassium inward currents, and
      only minimal D-aspartate-induced transporter currents. Astrocytes of all groups
      showed kainate-induced inward currents. We conclude that most of the astrocytes
      serve as a buffer system of excess extracellular glutamate and potassium;
      however, a distinct cell population (NG2-positive, A-type potassium currents) may
      play an important role for network plasticity.

PMID- 14960608
TI  - Optical mapping of the functional organization of the rat trigeminal nucleus:
      initial expression and spatiotemporal dynamics of sensory information transfer
      during embryogenesis.
AB  - We examined the functional organization of the rat trigeminal nuclear complex and
      its developmental dynamics using a multiple-site optical recording technique.
      Brainstem preparations were dissected from embryonic day 12 (E12)-E16 rat
      embryos, and stimulation was applied individually to the three branches of the
      trigeminal nerve (V1-V3). The action potential activity of presynaptic fibers was
      detected from E13, and the glutamate-mediated postsynaptic response was
      significantly observed from E15 on. At E14, the evoked signals usually consisted
      of only the action potential-related fast component. However, when extracellular
      Mg2+ was removed, a significant dl-2-amino-5-phosphonovaleric acid-sensitive slow
      component appeared. These results suggest that postsynaptic function mediated by
      NMDA receptors is latently generated as early as E14. The response area of the
      three branches of the trigeminal nerve showed some functional somatotopic
      organization, with the ophthalmic (V1) nerve area medially located and the
      mandibular (V3) nerve area laterally located. The center of the trigeminal
      nuclear complex in which the activity of neurons and synaptic function was
      greatest shifted caudally with development, suggesting that the functional
      architecture of the trigeminal nuclear complex is not fixed but changes
      dynamically during embryogenesis. By electron microscopy, we could not observe
      clear correlations between functional data and morphological information; when we
      surveyed E16 preparations, we could not identify typical synaptic structures
      between the 1,1'-dioctyldecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate
      labeled trigeminal nerve terminals and the neurons in the trigeminal nuclear
      complex. This implies that postsynaptic function in the trigeminal nuclear
      complex is generated before the appearance of the morphological structure of
      conventional synapses.

PMID- 14960609
TI  - Regionally specific distribution of corticospinal synapses because of activity
      dependent synapse elimination in vitro.
AB  - We have shown previously that the corticospinal tract (CST) with functional
      connections can be reconstructed in vitro in slice cocultures. Using that system,
      we stimulated the deep cortical layer and recorded field EPSPs (fEPSPs) along a
      100 microm-interval lattice in the spinal gray matter. The specific, spatial
      synapse distribution on the dorsal side at 14 d in vitro (DIV) basically
      corresponded to the in vivo area in which CST axons terminate. Anterograde
      labeling of corticospinal axons with biocytin showed a similar terminal
      distribution on that side. In vitro development of synapse spatial distribution
      was investigated. fEPSPs were recorded all across the gray matter at 7 DIV, but
      amplitudes began to decrease on the ventral side at 9 DIV, dorsal-dominant
      distribution being nearly complete at 14 DIV. Anterograde labeling showed that
      the decrease in fEPSP amplitudes was associated with a decrease in the number of
      axon terminals on the ventral area. Decreases in the synaptic responses and
      terminals were blocked by applications of D-2-amino-5-phosphonovaleric acid and
      tetrodotoxin, whereas 6-cyano-7-nitroquinoxaline-2,3-dione had a partial effect.
      These findings suggest that this regressive event, which occurs during
      development, is activity and NMDA dependent. Retrograde labeling with two colors
      of beads and an electrophysiological study that investigated the axon reflex
      showed that at 7 DIV most corticospinal neurons project to both the ventral and
      dorsal spinal cord, indicating that synapse decrease on the ventral side is
      attributable primarily to axon branch elimination rather than to death of
      cortical cells that send axons solely to that side.

PMID- 14960610
TI  - The basolateral amygdala interacts with the medial prefrontal cortex in
      regulating glucocorticoid effects on working memory impairment.
AB  - Previous findings indicate that the basolateral complex of the amygdala (BLA)
      interacts with other brain regions in regulating stress hormone effects on memory
      functions. Lesions of the BLA or infusions of a beta-adrenoceptor antagonist into
      the BLA block glucocorticoid effects on both memory consolidation and retrieval
      when administered either systemically or directly into the hippocampus. The
      present experiments examined BLA and beta-adrenoceptor involvement in regulating
      glucocorticoid effects on spatial working memory, a task that depends on the
      medial prefrontal cortex (mPFC). Male Sprague Dawley rats with bilateral sham- or
      NMDA-induced lesions of the BLA received either corticosterone (1.0 or 3.0 mg/kg,
      i.p.) systemically or the specific glucocorticoid receptor agonist 11beta,17beta
      dihydroxy-6,21-dimethyl-17alpha-pregna-4,6-trien-20yn-3-one (RU 28362; 3.0 or
      10.0 ng in 0.5 microl) into the mPFC shortly before testing on a delayed
      alternation task in a T-maze. Both glucocorticoid treatments induced comparable
      impairments in working memory performance in sham-lesioned controls. Although
      lesions of the BLA alone did not affect working memory, BLA lesions blocked the
      impairment induced by either corticosterone or RU 28362. Likewise, systemic
      injections of the centrally acting beta-adrenoceptor antagonist propranolol (2.0
      mg/kg, i.p.) given before testing prevented corticosterone-induced working memory
      impairment. These findings indicate that BLA activity is essential for enabling
      glucocorticoid effects in the mPFC on working memory and suggest that stress
      hormone-induced modulation of working memory involves noradrenergic activation.

PMID- 14960611
TI  - A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows
      microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the
      spinal cord.
AB  - CNS lesions induce production of ECM molecules that inhibit axon regeneration.
      One major inhibitory family is the chondroitin sulfate proteoglycans (CSPGs).
      Reduction of their glycosaminoglycan (GAG) chains with chondroitinase ABC leads
      to increased axon regeneration that does not extend well past the lesion.
      Chondroitinase ABC, however, is unable to completely digest the GAG chains from
      the protein core, leaving an inhibitory "stub" carbohydrate behind. We used a
      newly designed DNA enzyme, which targets the mRNA of a critical enzyme that
      initiates glycosylation of the protein backbone of PGs, xylosyltransferase-1. DNA
      enzyme administration to TGF-beta-stimulated astrocytes in culture reduced
      specific GAG chains. The same DNA enzyme applied to the injured spinal cord led
      to a strong reduction of the GAG chains in the lesion penumbra and allowed axons
      to regenerate around the core of the lesion. Our experiments demonstrate the
      critical role of PGs, and particularly those in the penumbra, in causing
      regeneration failure in the adult spinal cord.

PMID- 14960612
TI  - A gephyrin-related mechanism restraining glycine receptor anchoring at GABAergic
      synapses.
AB  - Spinal cord neurons release glycine and GABA and accumulate glycine receptors
      (GlyRs) and GABA(A) receptors in the same postsynaptic densities. In contrast,
      supramedullar neurons prefer GABA as a neurotransmitter and exclude GlyRs from
      postsynaptic anchoring. The general aim of the present study was to elucidate the
      mechanisms underlying transmitter-appropriate receptor accumulation at inhibitory
      synapses. Specifically, we intended to clarify the molecular basis for the
      prohibition of GlyR accumulation in the postsynaptic densities of GABAergic
      synapses. A green fluorescent protein (GFP)-tagged gephyrin-binding loop of the
      GlyR beta subunit (GFP::betaL) was used as a surrogate for full-length receptors
      to characterize the GlyR binding capacity of postsynaptic gephyrins in
      transfected neurons. Both in spinal cord neurons (SCNs) and hippocampal neurons
      (HNs) GFP::betaL distribution displayed transmitter specificity; i.e.,
      postsynaptic accumulation of GFP::betaL was high opposite terminals able to
      release glycine and low opposite purely GABAergic terminals. When comparing SCN
      and HN cultures we found that the level of mRNA coding for gephyrin splice
      variants containing the cassette C5 (C5-gephyrins) was significantly higher in
      HNs. In HNs depleted of C5-gephyrins, both GFP::betaL and endogenous GlyRs
      accumulated at postsynaptic GABAergic sites. Accordingly in SCNs, GFP-tagged C5
      gephyrin displayed a preferential postsynaptic accumulation opposite GABAergic
      synapses. Comparison of glycinergic, mixed, and GABAergic synapses in SCNs showed
      that the degree of GlyR accumulation was inversely related to the amount of
      postsynaptic C5-gephyrin. These results identify the C5 splice variant of
      gephyrin as a factor regulating the transmitter-appropriate degree of GlyR
      accumulation at inhibitory synapses.

PMID- 14960613
TI  - Differential localization of glutamate receptor subunits at the Drosophila
      neuromuscular junction.
AB  - The subunit composition of postsynaptic neurotransmitter receptors is a key
      determinant of synaptic physiology. Two glutamate receptor subunits, Drosophila
      glutamate receptor IIA (DGluRIIA) and DGluRIIB, are expressed at the Drosophila
      neuromuscular junction and are redundant for viability, yet differ in their
      physiological properties. We now identify a third glutamate receptor subunit at
      the Drosophila neuromuscular junction, DGluRIII, which is essential for
      viability. DGluRIII is required for the synaptic localization of DGluRIIA and
      DGluRIIB and for synaptic transmission. Either DGluRIIA or DGluRIIB, but not
      both, is required for the synaptic localization of DGluRIII. DGluRIIA and
      DGluRIIB compete with each other for access to DGluRIII and subsequent
      localization to the synapse. These results are consistent with a model of a
      multimeric receptor in which DGluRIII is an essential component. At single
      postsynaptic cells that receive innervation from multiple motoneurons, DGluRIII
      is abundant at all synapses. However, DGluRIIA and DGluRIIB are differentially
      localized at the postsynaptic density opposite distinct motoneurons. Hence,
      innervating motoneurons may regulate the subunit composition of their receptor
      fields within a shared postsynaptic cell. The capacity of presynaptic inputs to
      shape the subunit composition of postsynaptic receptors could be an important
      mechanism for synapse-specific regulation of synaptic function and plasticity.

PMID- 14960614
TI  - Activation of phasic pontine-wave generator prevents rapid eye movement sleep
      deprivation-induced learning impairment in the rat: a mechanism for sleep
      dependent plasticity.
AB  - Animal and human studies of sleep and learning have demonstrated that training on
      various tasks increases subsequent rapid eye movement (REM) sleep and phasic
      pontine-wave (P-wave) activity, followed by improvement in performance on the
      learned task. It is well documented that REM sleep deprivation after learning
      trials blocks the expected improvement in performance on subsequent retesting.
      Our aim was to test whether experimentally induced P-wave generator activation
      could eliminate the learning impairment produced by post-training REM sleep
      deprivation. Rats were trained on a two-way active avoidance-learning task.
      Immediately thereafter, two groups of those rats received a control vehicle (100
      nl saline) microinjection and one group received a carbachol (50 ng in 100 nl
      saline) microinjection into the P-wave generator. The carbachol-injected group
      and one of the two control saline microinjected groups were selectively deprived
      of REM sleep during a 6 hr polygraphic recording session. All rats were then
      tested on the avoidance-learning task. The rats that received both the control
      saline injection and REM sleep deprivation showed learning deficits compared with
      the control saline-injected rats that were allowed to sleep normally. In
      contrast, the rats that received the carbachol microinjection and REM sleep
      deprivation demonstrated normal learning. These results demonstrate, for the
      first time, that carbachol-induced activation of the P-wave generator prevents
      the memory-impairing effects of post-training REM sleep deprivation. This
      evidence supports our hypothesis that the activation of the P-wave generator
      during REM sleep deprivation enhances a physiological process of memory, which
      occurs naturally during post-training REM sleep.

PMID- 14960615
TI  - Relationship between excitation and inhibition underlying size tuning and
      contextual response modulation in the cat primary visual cortex.
AB  - In the primary visual cortex (V1), the single-neuron response to a grating
      stimulus placed in the classical receptive field (CRF) is suppressed by a similar
      stimulus presented in the CRF surround. To assess the input mechanism underlying
      the surround suppression, we tested the effects of iontophoretically administered
      GABA(A)-receptor antagonist, bicuculline methiodide (BMI), for the 46 V1 neurons
      in anesthetized cats. First, the stimulus-size tuning curves were studied, with
      or without BMI administration, for each neuron by changing the size of the
      grating patch. During the BMI administration, the shape of the normalized size
      tuning curve did not change considerably. Second, the dependency of surround
      suppression on the orientation of the surround grating was examined. In the
      control, the surround suppression showed the clear orientation tuning that peaked
      at an orientation the same as the optimal orientation of the CRF response. The
      BMI administration did not change the orientation dependency of surround
      suppression. We also estimated the relative contribution of excitation and
      inhibition to the size and orientation tuning of surround suppression. It was
      concluded that cortical excitation and inhibition were well balanced, having
      similar tuning profiles for both stimulus size and orientation of the surround
      grating. Furthermore, surround stimuli used for V1 neurons suppressed the CRF
      response of neurons in the lateral geniculate nucleus. These results suggest that
      surround suppression is not primarily attributable to the intracortical
      inhibition, but because of a reduction of thalamocortical inputs, which drive the
      cortical excitation and inhibition, and a subsequent decrease in the cortical
      excitatory interactions.

PMID- 14960616
TI  - Neuronal activity and adenylyl cyclase in environment-dependent plasticity of
      axonal outgrowth in Drosophila.
AB  - The development of the nervous system is influenced by environmental factors.
      Among all environmental factors, temperature belongs to a unique category.
      Besides activating some specific sensory pathways, it exerts nonspecific,
      pervasive effects directly on the entire nervous system, especially in exothermic
      species. This study uses mutants to genetically discover how temperature affects
      nerve terminal arborization at larval neuromuscular junctions of Drosophila. It
      is known that hyperexcitability in K(+) channel mutants leads to enhanced
      ramification of larval nerve terminals. Elevated cAMP levels in dunce mutants
      with reduced phosphodiesterase activity also cause enhanced arborization. These
      genetic alterations are thought to perturb mechanisms relevant to activity
      dependent neural plasticity, in which neuronal activity activates the cAMP
      pathway, and consequently affect nerve terminal arborization by regulating
      expression of adhesion molecules. Here we demonstrate the robust influence of
      rearing temperature on motor nerve terminal arborization. Analysis of ion channel
      and cAMP pathway mutants indicates that this temperature-dependent plasticity is
      mediated via neuronal activity changes linked to mechanisms controlled by the
      rutabaga-encoded adenylyl cyclase.

PMID- 14960617
TI  - Enhancement of working memory in aged monkeys by a sensitizing regimen of
      dopamine D1 receptor stimulation.
AB  - A natural consequence of aging is a loss of dopamine function and associated
      deficits in working memory in both human and nonhuman primates. Specifically,
      deficiency of D1 receptor signaling has been implicated in age-related cognitive
      decline. Here, we report that an intermittent, sensitizing regimen of the D1
      dopamine agonist ABT-431 dramatically enhances working memory performance in aged
      rhesus monkeys, while either producing impairment or having little effect on
      performance in young adult monkeys. Importantly, cognitive enhancement in the
      aged monkeys was still evident for >1 year after cessation of D1 treatment.
      Because intermittent exposure to low doses of amphetamine and other stimulants
      has been shown to enhance responsiveness to subsequent stimulant exposure, our
      findings suggest that sensitization of D1 signaling may provide a novel
      neurobiological mechanism for improving a core cognitive process in conditions in
      which dopamine function has deteriorated, such as in normal aging and Parkinson's
      disease.

PMID- 14960618
TI  - Nonopioid actions of intrathecal dynorphin evoke spinal excitatory amino acid and
      prostaglandin E2 release mediated by cyclooxygenase-1 and -2.
AB  - Spinal dynorphin is hypothesized to contribute to the hyperalgesia that follows
      tissue and nerve injury or sustained morphine exposure. We considered that these
      dynorphin actions are mediated by a cascade involving the spinal release of
      excitatory amino acids and prostaglandins. Unanesthetized rats with lumbar
      intrathecal injection and loop dialysis probes received intrathecal NMDA,
      dynorphin A(1-17), or dynorphin A(2-17). These agents elicited an acute release
      of glutamate, aspartate, and taurine but not serine. The dynorphin peptides and
      NMDA also elicited a long-lasting spinal release of prostaglandin E2.
      Prostaglandin release evoked by dynorphin A(2-17) or NMDA was blocked by the NMDA
      antagonist amino-5-phosphonovalerate as well the cyclooxygenase (COX) inhibitor
      ibuprofen. To identify the COX isozyme contributing to this release, SC 58236, a
      COX-2 inhibitor, was given and found to reduce prostaglandin E2 release evoked by
      either agent. Unexpectedly, the COX-1 inhibitor SC 58560 also reduced dynorphin
      A(2-17)-induced, but not NMDA-induced, release of prostaglandin E2. These
      findings reveal a novel mechanism by which elevated levels of spinal dynorphin
      seen in pathological conditions may produce hyperalgesia through the release of
      excitatory amino acids and in part by the activation of a constitutive spinal COX
      1 and -2 cascade.

PMID- 14960619
TI  - Selective ablation of a class of amacrine cells alters spatial processing in the
      retina.
AB  - Several recent studies have suggested that the spatial tuning of retinal ganglion
      cells may be a more complex process than previously thought. The working
      hypothesis for many years was that the tuning was shaped by operations performed
      in the first synaptic layer of the retina, but recent work shows that operations
      in the second synaptic layer, involving amacrine cells, also play a significant
      role (Cook and McReynolds, 1998; Taylor, 1999; Flores-Herr et al., 2001).
      Although it is clear that amacrine cells are involved, the precise roles of the
      different amacrine subtypes in the many aspects of spatial tuning have not yet
      been established. Here we used a cell class ablation method to remove one
      subtype, the neuropeptide Y-expressing cells (NPY cells), and tapped into a part
      of the circuitry that tunes ganglion cells toward large spatial patterns (low
      spatial frequencies). When the subtype was ablated, ganglion cells tuned toward
      low spatial frequencies, both ON- and OFF-type cells, lost this preferential
      tuning. The effect was specific because ablation of another amacrine subtype did
      not produce it. Further analysis showed that the change in tuning was
      attributable to a decrease in the receptive field surround size of the ganglion
      cell. Other parameters, such as the size, strength, and asymmetry of the center
      and the strength of the surround, were not statistically significantly affected.
      These results thus show a mechanism for tuning cells to low spatial frequencies;
      an operation in the second synaptic layer, mediated by NPY cells, extends the
      surround of the ganglion cell.

PMID- 14960620
TI  - Novel features of cryptochrome-mediated photoreception in the brain circadian
      clock of Drosophila.
AB  - In Drosophila, light affects circadian behavioral rhythms via at least two
      distinct mechanisms. One of them relies on the visual phototransduction cascade.
      The other involves a presumptive photopigment, cryptochrome (cry), expressed in
      lateral brain neurons that control behavioral rhythms. We show here that cry is
      expressed in most, if not all, larval and adult neuronal groups expressing the
      PERIOD (PER) protein, with the notable exception of larval dorsal neurons (DN2s)
      in which PER cycles in antiphase to all other known cells. Forcing cry expression
      in the larval DN2s gave them a normal phase of PER cycling, indicating that their
      unique antiphase rhythm is related to their lack of cry expression. We were able
      to directly monitor CRY protein in Drosophila brains in situ. It appeared highly
      unstable in the light, whereas in the dark, it accumulated in both the nucleus
      and the cytoplasm, including some neuritic projections. We also show that dorsal
      PER-expressing brain neurons, the adult DN1s, are the only brain neurons to
      coexpress the CRY protein and the photoreceptor differentiation factor GLASS.
      Studies of various visual system mutants and their combination with the cry(b)
      mutation indicated that the adult DN1s contribute significantly to the light
      sensitivity of the clock controlling activity rhythms, and that this contribution
      depends on CRY. Moreover, all CRY-independent light inputs into this central
      behavioral clock were found to require the visual system. Finally, we show that
      the photoreceptive DN1 neurons do not behave as autonomous oscillators, because
      their PER oscillations in constant darkness rapidly damp out in the absence of
      pigment-dispersing-factor signaling from the ventral lateral neurons.

PMID- 14960621
TI  - Dysregulation in the suicide brain: mRNA expression of corticotropin-releasing
      hormone receptors and GABA(A) receptor subunits in frontal cortical brain region.
AB  - Corticotropin-releasing hormone (CRH) and GABA have been implicated in
      depression, and there is reason to believe that GABA may influence CRH
      functioning. The levels of CRH, and mRNA for CRH-binding protein, CRH1, and CRH2
      receptors, as well as various GABA(A) receptor subunits (alpha1, alpha2, alpha3,
      alpha4, alpha5, delta, and gamma2), were determined in several frontal cortical
      brain regions of depressed suicide victims and nondepressed individuals who had
      not died by suicide. Relative to the comparison group, CRH levels were elevated
      in frontopolar and dorsomedial prefrontal cortex, but not in the ventrolateral
      prefrontal cortex of suicide victims. Conversely, using quantitative PCR
      analyses, it was observed that, in frontopolar cortex, mRNA for CRH1, but not
      CRH2, receptors were reduced in suicide brains, possibly secondary to the high
      levels of CRH activity. In addition, mRNA of the alpha1, alpha3, alpha4, and
      delta receptor subunits was reduced in the frontopolar region of suicide victims.
      Interestingly, a partial analysis of the GABA(A) receptor functional genome
      revealed high cross-correlations between subunit expression in cortical regions
      of nondepressed individuals, suggesting a high degree of coordinated gene
      regulation. However, in suicide brains, this regulation was perturbed,
      independent of overall subunit abundance. These findings raise the possibility
      that the CRH and GABA(A) receptor subunit changes, or the disturbed coordination
      between these GABA(A) receptor subunits, contribute to depression and/or
      suicidality or are secondary to the illness/distress associated with it.

PMID- 14960622
TI  - ORP150/HSP12A regulates Purkinje cell survival: a role for endoplasmic reticulum
      stress in cerebellar development.
AB  - The endoplasmic reticulum (ER) stress response contributes to neuronal survival
      in ischemia and neurodegenerative processes. ORP150 (oxygen-regulated protein
      150)/HSP12A (heat shock protein 12A), a novel stress protein located in the ER,
      was markedly induced in Purkinje cells maximally at 4-8 d after birth, a
      developmental period corresponding to their vulnerability to cell death. Both
      terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labeling
      analysis and immunostaining using anti-activated caspase-3 antibody revealed that
      transgenic mice with targeted neuronal overexpression of ORP150 (Tg ORP150)
      displayed diminished cell death in the Purkinje cell layer and increased numbers
      of Purkinje cells up to 40 d after birth (p < 0.01), compared with those observed
      in heterozygous ORP150/HSP12A-deficient (ORP150+/-) mice and wild-type
      littermates (ORP150+/+). Cultured Purkinje cells from Tg ORP150 mice displayed
      resistance to both hypoxia- and AMPA-induced stress. Behavioral analysis, using
      rotor rod tasks, indicated impairment of cerebellar function in Tg ORP150
      animals, consistent with the concept that enhanced survival of Purkinje cells
      results in dysfunction. These data suggest that ER chaperones have a pivotal role
      in Purkinje cell survival and death and thus may highlight the importance of ER
      stress in neuronal development.

PMID- 14960623
TI  - Multiple roles for slits in the control of cell migration in the rostral
      migratory stream.
AB  - The subventricular zone (SVZ) contains undifferentiated cells, which proliferate
      and generate olfactory bulb (OB) interneurons. Throughout life, these cells leave
      the SVZ and migrate along the rostral migratory stream (RMS) to the OB where they
      differentiate. In vitro, the septum and the choroid plexus (CP) secrete repulsive
      factors that could orient the migration of OB precursors. Slit1 and Slit2, two
      known chemorepellents for developing axons, can mimic this effect. We show here
      that the Slit receptors Robo2 and Robo3/Rig-1 are expressed in the SVZ and the
      RMS and that Slit1 and Slit2 are still present in the adult septum. Using Slit1/2
      deficient mice, we found that Slit1 and Slit2 are responsible for both the septum
      and the CP repulsive activity in vitro. In adult mice lacking Slit1, small chains
      of SVZ-derived cells migrate caudally into the corpus callosum, supporting a role
      for Slits in orienting the migration of SVZ cells. Surprisingly, in adult mice,
      Slit1 was also expressed by type A and type C cells in the SVZ and RMS,
      suggesting that Slit1 could act cell autonomously. This hypothesis was tested
      using cultures of SVZ explants or isolated neurospheres from Slit1-/- or Slit1+/-
      mice. In both types of cultures, the migration of SVZ cells was altered in the
      absence of Slit1. This suggests that the regulation of the migration of OB
      precursors by Slit proteins is complex and not limited to repulsion.

PMID- 14960624
TI  - Postsynaptic density assembly is fundamentally different from presynaptic active
      zone assembly.
AB  - The cellular mechanisms involved in the formation of the glutamatergic
      postsynaptic density (PSD) are mainly unknown. Previous studies have indicated
      that PSD assembly may occur in situ by a gradual recruitment of postsynaptic
      molecules, whereas others have suggested that the PSD may be assembled from
      modular transport packets assembled elsewhere. Here we used cultured hippocampal
      neurons and live cell imaging to examine the process by which PSD molecules from
      different layers of the PSD are recruited to nascent postsynaptic sites. GFP
      tagged NR1, the essential subunit of the NMDA receptor, and ProSAP1/Shank2 and
      ProSAP2/Shank3, scaffolding molecules thought to reside at deeper layers of the
      PSD, were recruited to new synaptic sites in gradual manner, with no obvious
      involvement of discernible discrete transport particles. The recruitment kinetics
      of these three PSD molecules were remarkably similar, which may indicate that PSD
      assembly rate is governed by a common upstream rate-limiting process. In
      contrast, the presynaptic active zone (AZ) molecule Bassoon was observed to be
      recruited to new presynaptic sites by means of a small number of mobile packets,
      in full agreement with previous studies. These findings indicate that the
      assembly processes of PSDs and AZs may be fundamentally different.

PMID- 14960625
TI  - A1 adenosine receptor upregulation and activation attenuates neuroinflammation
      and demyelination in a model of multiple sclerosis.
AB  - The neuromodulator adenosine regulates immune activation and neuronal survival
      through specific G-protein-coupled receptors expressed on macrophages and
      neurons, including the A1 adenosine receptor (A1AR). Here we show that A1AR null
      (A1AR-/-) mice developed a severe progressive-relapsing form of experimental
      allergic encephalomyelitis (EAE) compared with their wild-type (A1AR+/+)
      littermates. Worsened demyelination, axonal injury, and enhanced activation of
      microglia/macrophages were observed in A1AR-/- animals. In addition, spinal cords
      from A1AR-/- mice demonstrated increased proinflammatory gene expression during
      EAE, whereas anti-inflammatory genes were suppressed compared with A1AR+/+
      animals. Macrophages from A1AR-/- animals exhibited increased expression of the
      proinflammatory genes, interleukin-1beta, and matrix metalloproteinase-12 on
      immune activation when matched with A1AR+/+ control cells. A1AR-/- macrophage
      derived soluble factors caused significant oligodendrocyte cytotoxicity compared
      with wild-type controls. The A1AR was downregulated in microglia in A1AR+/+ mice
      during EAE accompanied by neuroinflammation, which recapitulated findings in
      multiple sclerosis (MS) patients. Caffeine treatment augmented A1AR expression on
      microglia, with ensuing reduction of EAE severity, which was further enhanced by
      concomitant treatment with the A1AR agonist, adenosine amine congener. Thus,
      modulation of neuroinflammation by the A1AR represents a novel mechanism that
      provides new therapeutic opportunities for MS and other demyelinating diseases.

PMID- 14960630
TI  - Incremental prognostic implications of brain natriuretic peptide, cardiac
      sympathetic nerve innervation, and noncardiac disorders in patients with heart
      failure.
AB  - Plasma brain natriuretic peptide (BNP) level and cardiac autonomic function are
      closely related to prognosis in patients with heart failure. However, their
      correlation and incremental prognostic values in human heart failure are unclear.
      We sought to evaluate the correlation between BNP level and cardiac sympathetic
      innervation assessed by (123)I-metaiodobenzylguanidine ((123)I-MIBG) and the
      prognostic value of combined assessment of risk factors for mortality in patients
      with heart failure. METHODS: After conventional examinations and measurements of
      plasma BNP level and heart-to-mediastinum ratio (HMR) of cardiac (123)I-MIBG
      activity, 158 patients with heart failure were prospectively followed with an
      endpoint of cardiac death for 16 mo. RESULTS: Fifteen deaths due to pump failure
      and 2 sudden cardiac deaths were documented. Plasma BNP level correlated with HMR
      significantly but not so tightly (r = 0.330, P < 0.0001). Univariate analysis
      identified plasma BNP level, HMR, chronic renal dysfunction, diabetes mellitus,
      age, and use of nitrates as significant predictors of fatal pump failure, and
      multivariate Cox analysis showed that plasma BNP level was the most powerful
      predictor of cardiac death. Patients with both plasma BNP level of > or = 172
      pg/mL and late HMR of < or =1.74 had a greater annual rate of fatal pump failure
      than did those without (17.5%/y vs. 0%-3.9%/y, respectively). The hazard ratio of
      plasma BNP level (7.2) or cardiac (123)I-MIBG activity (10.1) increased to 34.4
      when both variables were used, and prevalence of fatal pump failure significantly
      increased from 22% to 62.5% when diabetes mellitus and chronic renal dysfunction
      were present with a higher plasma BNP level and low cardiac (123)I-MIBG activity.
      CONCLUSION: Plasma BNP level is a stronger predictor than other risk factors for
      mortality in heart failure patients and is statistically significantly, but
      roughly, related to cardiac sympathetic nerve innervation. Impaired cardiac
      sympathetic nerve innervation and the presence of diabetes mellitus and chronic
      renal dysfunction, however, improve risk stratification of patients with heart
      failure and increased plasma BNP concentration.

PMID- 14960631
TI  - Myocardial perfusion imaging using gated SPECT in heart failure patients
      undergoing cardiac resynchronization therapy.
AB  - Cardiac resynchronization therapy (CRT) by biventricular pacing is indicated in
      patients with severe heart failure and left bundle branch block who remain
      symptomatic despite optimal medical therapy. The relationship between baseline
      resting perfusion pattern and hemodynamic response to CRT has not been fully
      investigated. We tested the usefulness of perfusion gated SPECT for baseline
      evaluation and follow-up of these patients. METHODS: In 20 patients, we performed
      gated SPECT before CRT and at the 3-mo follow up. Left ventricular (LV) ejection
      fraction (EF), end-diastolic (ED) and end-systolic (ES) volume indexes (VI), and
      wall motion score index (WMSI) were measured and compared with clinical outcome.
      RESULTS: One patient died before follow-up. The 19 remaining patients were
      classified into 1 of 2 groups according to the presence (group A) or absence
      (group B) of a significant severe perfusion defect at baseline before CRT. At the
      3-mo follow-up, 6 of 10 group A and 8 of 9 group B patients had an improvement in
      New York Heart Association class. In both groups, quality of life, 6-min walking
      distance, and WMSI significantly improved. In group A, no significant change was
      registered in LVEF, LVEDVI, or LVESVI. In group B, LVEF increased from 23.1% +/-
      8% to 27.1% +/- 11% (P < 0.03) and LVEDVI and LVESVI decreased from 159 +/- 70 mL
      to 135 +/- 68 mL (P < 0.02) and from 127 +/- 67 mL to 104 +/- 65 mL (P < 0.01),
      respectively. CONCLUSION: Perfusion gated SPECT appears useful to characterize
      and follow up candidates for CRT. Despite clinical improvement, patients with
      severe resting perfusion defects do not show significant improvement in LVEF or
      reduction in LV volumes.

PMID- 14960632
TI  - Postinjection transmission scanning in myocardial 18F-FDG PET studies using both
      filtered backprojection and iterative reconstruction.
AB  - The aim of the present study was to evaluate the effect of postinjection
      transmission scanning (Post-Tx) on both the qualitative interpretation and the
      quantitative analysis of cardiac (18)F-FDG PET images. Furthermore, the accuracy
      of 2 different methods to correct for emission contamination was studied. An
      additional aim of this study was to compare images reconstructed with both
      standard filtered backprojection (FBP) and an iterative reconstruction algorithm
      (ordered-subset maximization expectation [OSEM]). METHODS: Sixteen patients
      underwent dynamic (18)F-FDG imaging. Both before injection of (18)F-FDG and after
      completing the emission scan, a 10-min transmission scan was performed (Pre-Tx
      and Post-Tx, respectively). Images were reconstructed using both FBP and OSEM.
      The emission study reconstructed with Pre-Tx was considered to be the gold
      standard. Emission studies were also reconstructed with Post-Tx, with and without
      correction for emission contamination. Correction for emission contamination was
      performed with either transmission image segmentation (TIS) or by estimating the
      emission bias from the last emission frame (dwell profile [DP] method). All
      images were then compared by calculating ratios of (18)F-FDG activity between
      corresponding myocardial segments in each patient. Furthermore, qualitative
      grading of (18)F-FDG uptake was compared between the studies. RESULTS: The mean
      ratio of (18)F-FDG activity between segments from FBP-Post and FBP-Pre was 0.78
      +/- 0.08. When TIS and DP were used, the mean ratios were 0.80 +/- 0.07 and 0.94
      +/- 0.06, respectively. The use of OSEM resulted in, on average, 2% lower values
      for (18)F-FDG activity as compared with FBP. The mean normalized (18)F-FDG uptake
      was higher in FBP-Post, especially in segments with decreased (18)F-FDG activity.
      Only in the case of DP were no significant differences observed as compared with
      FBP-Pre. In general, qualitative analysis of the images showed that the agreement
      between the reconstruction methods was comparable with the reproducibility of FBP
      Pre. CONCLUSION: Post-Tx for attenuation correction in cardiac (18)F-FDG PET
      scans resulted in substantial underestimation of (18)F-FDG activity. More
      accurate results were obtained with correction for emission contamination using
      DP. Differences in visual assessment of (18)F-FDG images were small. Finally,
      iterative reconstruction could be used as an alternative to FBP in static (18)F
      FDG imaging of the heart.

PMID- 14960633
TI  - Comparison of gated PET with MRI for evaluation of left ventricular function in
      patients with coronary artery disease.
AB  - The aim of this study was to compare left ventricular (LV) volumes and regional
      wall motion determined by PET with those determined by the reference technique,
      cardiovascular MRI. METHODS: LV end-diastolic volume (LVEDV), LV end-systolic
      volume (LVESV), and LV ejection fraction (LVEF) were measured and regional wall
      motion was scored in 38 patients with chronic coronary artery disease by both
      gated (18)F-FDG PET and MRI. A 9-segment model was used for PET and MRI to assess
      regional wall motion. RESULTS: Good correlations were observed between MRI and
      gated PET for all parameters (r values ranging from 0.91 to 0.96). With PET,
      there was a significant but small underestimation of LVEDV and LVEF. Mean +/- SD
      LVEDV, LVESV, and LVEF for MRI were 131 +/- 57 mL, 91 +/- 12 mL, and 33% +/- 12%,
      respectively, and those for gated PET were 117 +/- 56 mL, 85 +/- 51 mL, and 30%
      +/- 11%, respectively. For regional wall motion, an agreement of 85% was found,
      with a kappa-statistic of 0.79 (95% confidence interval, 0.70-0.89; SE, 0.049).
      CONCLUSION: LV volumes, LVEF, and regional wall motion can be assessed with gated
      (18)F-FDG PET and correlate well with these parameters assessed by MRI.

PMID- 14960634
TI  - Automatic quantification of myocardial perfusion stress-rest change: a new
      measure of ischemia.
AB  - In myocardial perfusion SPECT (MPS), ischemia is typically quantified as the
      difference between stress and rest defect sizes obtained by separate comparisons
      with stress and rest normal limits. Such an approach is not optimal because
      images are not compared directly with each other and a complex set of stress and
      rest normal limits is required. METHODS: We developed a fully automatic technique
      to quantify stress-rest change. We applied it to 204 patients whose SPECT images
      were acquired using a same-day dual-isotope (99m)Tc/(201)Tl protocol and on whom
      coronary angiography had been performed. A 10-parameter registration of rest and
      stress images was performed by an iterative search of best translational,
      rotational, scaling, and optimal stress-rest count normalization parameters.
      Identical stress-rest 3-dimensional left ventricle (LV) contours were
      automatically derived from stress images. Integrated deficit counts (normalized
      rest-stress) within the LV volume were derived from registered image pairs. A
      global measure of ischemia (ISCH) was calculated as the ratio of the total
      deficit stress LV counts to the total rest LV counts. RESULTS: Registration and
      derivation of quantitative measures were fully automatic. The average processing
      time was <40 s on a 2-GHz processor. When compared for prediction of stenosis,
      the area under the receiver operating characteristic curve (0.88 +/- 0.03) was
      significantly better for ISCH than that obtained by existing quantitative
      approaches, which use reference databases (0.80-0.82 +/- 0.03). The normalized
      stress-rest change could be visualized and localized directly on raw patient
      images using overlay display. CONCLUSION: Automatic stress-rest MPS image
      registration allows a direct estimation of ischemia from SPECT that does not
      require comparisons with normal limits.

PMID- 14960635
TI  - Integrated software for the analysis of brain PET/SPECT studies with partial
      volume-effect correction.
AB  - We present software for integrated analysis of brain PET studies and coregistered
      segmented MRI that couples a module for automated placement of regions of
      interest (ROI) with 4 alternative methods for partial-volume-effect correction
      (PVEc). The accuracy and precision of these methods have been measured using 4
      simulated (18)F-FDG PET studies with increasing degrees of atrophy. METHODS: The
      software allows the application of a set of labels, defined a priori in the
      Talairach space, to segmented and coregistered MRI. Resulting ROIs are then
      transferred onto the PET study, and corresponding values are corrected according
      to the 4 PVEc techniques under investigation, providing corresponding corrected
      values. To evaluate the PVEc techniques, the software was applied to 4 simulated
      (18)F-FDG PET studies, introducing increasingly larger experimental errors,
      including errors in coregistration (0- to 6-pixel misregistration), segmentation
      (-13.7% to 14.1% gray matter [GM] volume change) and resolution estimate errors (
      16.9% to 26.8% full-width-at-half-maximum mismatch). RESULTS: Even in the absence
      of segmentation and coregistration errors, uncorrected PET values showed -37.6%
      GM underestimation and 91.7% WM overestimation. Voxel-based correction only for
      the loss of GM activity as a result of spill-out onto extraparenchymal tissues
      left a residual underestimation of GM values (-21.2%). Application of the method
      that took into account both spill-in and spill-out effects between any possible
      pair of ROIs (R-PVEc) and of the voxel-based method that corrects also for the WM
      activity derived from R-PVEC (mMG-PVEc) provided an accuracy above 96%. The
      coefficient of variation of the GM ROIs, a measure of the imprecision of the GM
      concentration estimates, was 8.5% for uncorrected PET data and decreased with
      PVEc, reaching 6.0% for mMG-PVEc. Coregistration errors appeared to be the major
      determinant of the imprecision. CONCLUSION: Coupling of automated ROI placement
      and PVEc provides a tool for integrated analysis of brain PET/MRI data, which
      allows a recovery of true GM ROI values, with a high degree of accuracy when R
      PVEc or mMG-PVEc is used. Among the 4 tested PVEc methods, R-PVEc showed the
      greatest accuracy and is suitable when corrected images are not specifically
      needed. Otherwise, if corrected images are desired, the mMG-PVEc method appears
      the most adequate, showing a similar accuracy.

PMID- 14960636
TI  - Efficacy assessment of cerebral arterial bypass surgery using statistical
      parametric mapping and probabilistic brain atlas on basal/acetazolamide brain
      perfusion SPECT.
AB  - The efficacy of cerebral arterial bypass surgery was assessed on brain perfusion
      SPECT using statistical parametric mapping (SPM) and a probabilistic brain atlas.
      METHODS: Fifteen patients with ischemia in the internal carotid artery (ICA)
      territory and 21 age-matched healthy volunteers were enrolled. (99m)Tc-HMPAO
      basal/acetazolamide brain perfusion SPECT was performed 2 wk before and after
      bypass surgery and also on a healthy control group. Using SPM analysis, group
      comparisons were made between pre- and postoperative SPECT for each
      basal/acetazolamide image, and improvements of perfusion and perfusion reserve
      were assessed. The number of significant voxels on the SPM analysis was defined
      as the extent of ischemia. With the use of the probabilistic brain atlas, the
      counts for the cerebral lobes and the ICA territory were automatically calculated
      for each image and compared. RESULTS: The group comparisons by SPM between
      patients and healthy volunteers showed a significant improvement in general
      perfusion status in the ICA territory. The improvement in perfusion reserve was
      more extensive than the improvement in perfusion. The extent of ischemia was also
      significantly decreased after surgery (1,693 +/- 2,604 to 371 +/- 523 voxels in
      basal images, P = 0.060; 11,879 +/- 6,449 to 5,997 +/- 3,864 voxels in
      acetazolamide images, P = 0.005). In the analysis using the probabilistic brain
      atlas, the preoperatively decreased perfusion was normalized after surgery, but a
      residual decrease in the perfusion reserve was also observed in the ICA
      territory. The counts in the volume of interest of the ICA territory were
      significantly improved (38.5 +/- 4.1 to 41.5 +/- 2.7 in basal images, P = 0.024;
      34.2 +/- 4.4 to 38.8 +/- 2.9 in acetazolamide images, P = 0.003). One patient
      showing a decrease in perfusion had a perioperative cerebral infarct. CONCLUSION:
      Using SPM and a probabilistic brain atlas, the perfusion, the perfusion reserve,
      and changes in both after cerebral arterial bypass surgery were effectively
      assessed and correlated well with physiologic reasoning.

PMID- 14960637
TI  - Reproducibility of 99mTc-TRODAT-1 SPECT measurement of dopamine transporters in
      Parkinson's disease.
AB  - Functional brain imaging targeting the presynaptic dopamine nerve terminal of the
      nigrostriatal system has been used for monitoring disease progression and
      evaluating therapeutic effectiveness in patients with Parkinson's disease (PD).
      (99m)Tc-TRODAT-1 binds with high selectivity to the dopamine transporters in the
      striatum and can be imaged with SPECT 4 h after injection. We studied the test
      and retest reproducibility of (99m)Tc-TRODAT-1 SPECT measures in patients with PD
      to assess the reliability of (99m)Tc-TRODAT-1 for longitudinal evaluation of the
      nigrostriatal dopaminergic function. METHODS: Each of 20 patients with PD
      underwent 2 (99m)Tc-TRODAT-1 SPECT scans at an interval of 2-3 wk. Patients were
      imaged 4 h after injection of 925 MBq (99m)Tc-TRODAT-1. Two imaging outcome
      measures were evaluated: the ratio of specific-striatal-to-nonspecific uptake and
      the striatal asymmetry index. For both measures, the test/retest variability was
      calculated. Reproducibility of the 2 outcome measures was evaluated in terms of
      intraclass correlation coefficient (ICC) and 95% limits of agreement. RESULTS:
      The mean ratio of specific-striatal-to-nonspecific uptake showed excellent
      test/retest reproducibility with a mean variability of 10.20%, an ICC of 0.95
      (95% confidence interval = 0.88-0.98), and 95% limits of agreement, ranging from 
      0.19 to 0.19. The striatal asymmetry index had larger test/retest variability
      (60.41%), a slightly smaller ICC of 0.86 (95% confidence interval = 0.65-0.95),
      and a wider range of 95% limits of agreement (-16.09 to 15.19). In addition,
      there was a significant negative correlation between the mean ratio of specific
      striatal-to-nonspecific uptake and the motor subscore of the Unified Parkinson's
      Disease Rating Scale in both test and retest conditions. CONCLUSION: Our data
      indicate that the imaging outcome expressed by the mean ratio of specific
      striatal-to-nonspecific uptake has an excellent test/retest reproducibility and
      correlates with disease severity. These findings suggest that (99m)Tc-TRODAT-1
      SPECT imaging is useful and feasible for measuring disease progression in PD.

PMID- 14960638
TI  - Respiratory gating for 3-dimensional PET of the thorax: feasibility and initial
      results.
AB  - Respiratory motion may reduce the sensitivity of (18)F-FDG PET for the detection
      of small pulmonary nodules close to the base of the lungs. This motion also
      interferes with attempts to use fused PET/CT images through software or combined
      PET/CT devices. This study was undertaken to assess the feasibility of
      respiratory gating for PET of the chest and the impact of respiratory motion on
      quantitative analysis. METHODS: Ten healthy subjects were enrolled in this study.
      Three-dimensional studies were acquired with 8 gates per respiratory cycle on a
      commercial PET scanner with a temperature-sensitive respiratory gating device
      built in-house. All scans were obtained over 42 cm of body length with 3 bed
      positions of 10 min each after injection of (18)F-FDG at 4.5 MBq/kg. The
      reconstructed images were assembled to produce gated whole-body volumes and
      maximum-intensity projections. The amplitude of respiratory motion of the kidneys
      (as a surrogate for diaphragmatic incursion) as well as the apex of the heart was
      measured in the coronal plane. Phantom studies were acquired to simulate the
      impact of respiratory motion on quantitative uptake measurements. RESULTS: The
      respiratory gating device produced a consistent, reliable trigger signal. All
      acquisitions were successful and produced reconstructed volumes with excellent
      image quality. Mean +/- SD motion amplitude and maximal motion amplitude values
      were 6.7 +/- 3.0 and 11.9 mm for the heart, 12.0 +/- 3.7 and 18.8 mm for the
      right kidney, and 11.1 +/- 4.8 and 17.1 mm for the left kidney, respectively. In
      phantom studies, the standardized uptake value for a 1-mL lesion was
      underestimated by 30% and 48% for the average and maximal respiratory motion
      values, respectively. CONCLUSION: Respiratory gating of PET of the thorax and
      upper abdomen is a practical and feasible approach that may improve the detection
      of small pulmonary nodules. Further work is planned to assess prospectively the
      diagnostic accuracy of this new method.

PMID- 14960639
TI  - Sentinel lymph node detection in patients with early-stage breast cancer:
      comparison of periareolar and subdermal/peritumoral injection techniques.
AB  - Periareolar (PA) injection offers several potential advantages over other
      techniques for visualizing sentinel lymph nodes (SLNs) in patients with early
      breast cancer. However, few studies have been published on this procedure. This
      study was designed to validate PA injection technique and compare it with the
      subdermal/peritumoral (SD/PT) injection technique. METHODS: The study included
      324 patients in whom 330 breast cancers (T) had been identified by biopsy. This
      population was divided in 4 groups: (A) 148 patients (150 T) in whom lymphatic
      mapping was performed by injecting radiotracer with the SD/PT technique; (B) 59
      patients (60 T) in whom lymphatic mapping was performed with a combination of
      blue dye injected with the PA technique and radiotracer injected with the SD/PT
      technique; (C) 58 patients (60 T) in whom blue dye was injected subdermally and
      radiotracer was injected periareolarly; and (D) 59 patients (60 T) in whom both
      blue dye and radiotracer were injected periareolarly. RESULTS: Concordances in
      the SLN detection rate between blue dye and radiotracer in groups B, C, and D
      were 98.1%, 100%, and 100%, respectively. The SLN identification rates with the
      PA technique were 98.3% and 95%, respectively, for radiotracer and blue dye. With
      the SD/PT technique, these rates were 90.5% and 88.3%, respectively, for
      radiotracer and blue dye. At lymphoscintigraphy, SLN visualization required the
      acquisition of late images (3 h after the injection) in 20% of patients who
      received PA injections and 39.5% of patients who received SD/PT injections.
      CONCLUSION: These findings validate the PA injection technique and underline some
      of its reported advantages in comparison with the SD/PT technique.

PMID- 14960640
TI  - 18F-FLT PET for visualization of laryngeal cancer: comparison with 18F-FDG PET.
AB  - The feasibility of (18)F-3'-fluoro-3'-deoxy-L-thymidine PET (FLT PET) for
      detecting laryngeal cancer was investigated and compared with (18)F-FDG PET.
      METHODS: Eleven patients diagnosed with or strongly suspected of having recurrent
      laryngeal cancer and 10 patients with histologically proven primary laryngeal
      cancer underwent attenuation-corrected (18)F-FLT PET imaging 60 min after
      injection of a median of 213 MBq (range, 175-400 MBq) (18)F-FLT and attenuation
      corrected (18)F-FDG PET imaging 90 min after injection of a median of 340 MBq
      (range, 165-650 MBq) (18)F-FDG. All patients were staged by endoscopy and CT
      according to the Union Internationale Contre la Cancer TNM staging system. All
      patients underwent biopsy of the laryngeal area after imaging. Lesions seen on
      (18)F-FDG PET and (18)F-FLT PET were compared with histopathologic results. Mean
      SUVs, maximum SUVs, and tumor-to-nontumor (TNT) ratios were calculated for (18)F
      FLT and (18)F-FDG. Wilcoxon nonparametric testing was used for comparison of
      (18)F-FDG with (18)F-FLT uptake. The Spearman correlation coefficient was used to
      correlate mean SUVs, maximum SUVs, and TNT ratios of (18)F-FDG PET and (18)F-FLT
      PET. Two-tailed P values < 0.05 were considered significant. RESULTS: (18)F-FDG
      PET and (18)F-FLT PET detected laryngeal cancer correctly in 15 of 17 patients.
      One lesion judged as positive on (18)F-FDG PET turned out to be normal tissue. Of
      2 lesions judged as positive on (18)F-FLT PET, 1 turned out to be inflammation
      and the other to be normal tissue. Maximum SUVs were 3.3 (range, 1.9-8.5) for
      (18)F-FDG and 1.6 (range, 1.0-5.7) for (18)F-FLT (P < 0.001). Mean SUVs were 2.7
      (range, 1.5-6.5) for (18)F-FDG and 1.2 (range, 0.8-3.8) for (18)F-FLT (P <
      0.001). TNT was 1.9 (range, 1.3-4.7) for (18)F-FDG and 1.5 (range, 1.1-3.5) for
      (18)F-FLT (P < 0.05). CONCLUSION: The numbers of laryngeal cancers detected with
      (18)F-FLT PET and (18)F-FDG PET were equal. In laryngeal cancer, the uptake of
      (18)F-FDG is higher than that of (18)F-FLT.

PMID- 14960641
TI  - Age-dependent variation of follicular size and expression of iodine transporters
      in human thyroid tissue.
AB  - The high sensitivity of the thyroid gland to the carcinogenic effects of
      radiation during childhood contrasts with the absence of demonstrable
      carcinogenic effects of radiation in adults. To better understand these age
      related variations, we studied follicular morphometry, functional status, and
      proliferative activity in 31 thyroid glands removed from relatives of medullary
      thyroid carcinoma patients, with ages ranging from 3 to 39 y. METHODS: The mean
      follicular diameter (MFD) was estimated, and immunohistochemistry was performed
      with antibodies directed to molecules involved in iodide transport (Na(+)/I(-)
      symporter [NIS], pendrin, and apical iodide transporter), in organification
      (thyroperoxidase [TPO] and Duox), in cell cycle and growth (Ki-67, cyclin A and
      D1, and galectin-3), and in angiogenesis (vascular endothelial growth factor and
      nitric oxide synthase III [NOSIII]). RESULTS: Compared with older patients,
      patients who were < or =12 y old had a smaller MFD (P < 0.001) and more
      frequently positive NIS, pendrin, and Duox (P < 0.01). Proliferation rate as
      indicated by cyclin A expression was also higher in patients < 12 y (P < 0.01)
      but peaked at the time of puberty. Staining for NIS, pendrin, TPO, Duox, and
      NOSIII was stronger in thyroid glands with a smaller MFD (P < 0.001). On multiple
      tests adjusted for age and thyroid mass, TPO, Duox, and NOSIII remained
      significantly correlated to MFD (P < 0.001), whereas staining for NIS and pendrin
      did not. This finding suggests that NIS and pendrin expression is related mainly
      to the age of the patient. CONCLUSION: Smaller follicles with a higher expression
      of proteins involved in iodide metabolism were found in younger children. In
      cases of radioiodine contamination in children, the result will be a higher
      radioactive concentration and, hence, higher radiation doses. This event may
      induce the development of thyroid cancer under conditions of accelerated
      proliferation, as evidenced at puberty.

PMID- 14960642
TI  - Impact of radioimmunoscintigraphy on definition of clinical target volume for
      radiotherapy after prostatectomy.
AB  - The goal of this study was to evaluate the role of radioimmunoscintigraphy (RIS)
      directed against prostate-specific membrane antigen in modifying
      postprostatectomy prostate fossa clinical target volume (CTV) definition.
      METHODS: The records of 25 postprostatectomy patients who received external-beam
      radiotherapy after prostatectomy and who underwent vessel-based RIS/planning CT
      registration were reviewed. For each patient, the CTV that would have been
      treated (CTV(pre)) before this registration was compared with that defined after
      the registration (CTV(post)). In addition, using a standard dose of 66 Gy in 2-Gy
      fractions, the corresponding bladder and rectum dose volume histograms were
      compared using 2 endpoints: volume receiving > or =60 Gy (V60) and area under the
      curve (AUC). RESULTS: The mean CTV(pre) vs. CTV(post) volumes were 24.4 vs. 35.0
      cm(3), respectively (P = 0.032). The V60 results for CTV(pre) and CTV(post) were
      32.7 vs. 41.0 cm(3), respectively, for the rectum (P = 0.168) and 33.9 vs. 46.6
      cm(3), respectively, for the bladder (P = 0.015). The AUC results for CTV(pre)
      and CTV(post) were 4,027 vs. 4,516 Gy x cm(3), respectively, for the rectum (P =
      0.396) and 4,782 vs. 5,561, respectively, for the bladder (P = 0.119). No
      Radiation Therapy Oncology Group grade 3, 4, or 5 (acute or late,
      gastrointestinal, or genitourinary) toxicity was observed. Two-year biochemical
      failure-free survival (with failure defined as 2 consecutive prostate-specific
      antigen rises above 0.2ng/mL) was 87% for the cohort. CONCLUSION: Incorporating
      RIS uptake resulted in significant modifications in CTV definition. The
      consequences of these modifications on the rectum V60 or AUC or on the bladder
      AUC were not significant, although the bladder V60 did increase. However,
      observed toxicity was low, with acceptable short-term biochemical control,
      suggesting that treatment to the modified CTV was tolerable.

PMID- 14960643
TI  - Lymphatic drainage routes of the gastric cardia visualized by lymphoscintigraphy.
AB  - This study was undertaken to assess the feasibility of lymphoscintigraphy of the
      gastric cardia and to identify the incidence of paraesophageal lymphatic
      drainage, precluding total gastrectomy with esophagojejunostomy as a potentially
      curative therapy for gastric cardia cancer. METHODS: Ten patients scheduled for
      esophagectomy with high-grade dysplasia or with esophageal cancer at least 3 cm
      above the esophagogastric junction were enrolled in this study. Preoperatively,
      111 MBq of(99m)Tc-labeled nanocolloid (n = 5) or sulfur colloid (n = 5) were
      injected into the submucosa of the tumor-free cardia. Subsequently,
      lymphoscintigraphy in combination with CT was obtained. Locoregional lymph node
      stations were measured for radioactivity by a gamma-probe intraoperatively and ex
      vivo in the resection specimen. RESULTS: In each patient, at least 1 radioactive
      lymph node station was detected. In total, 42 radioactive lymph node stations
      were detected by gamma-probe. Of those 42 areas, 38 (90%) were visible at
      preoperative lymphoscintigraphy. In the group of 5 patients in whom nanocolloid
      was used, a median of 2 (range, 1-4) node stations per patient was identified,
      whereas when sulfur colloid was administered a median of 6 (range, 4-8) active
      lymph node stations per patient could be detected (P < 0.002). Paraesophageal
      drainage was identified in 1 patient. CONCLUSION: Lymphoscintigraphy of the
      gastric cardia is feasible and can accurately determine the location of
      radioactive lymph nodes. Early paraesophageal lymphatic drainage is rare.

PMID- 14960644
TI  - Engineered liposomes for potential alpha-particle therapy of metastatic cancer.
AB  - Disseminated, metastatic cancer is frequently incurable. Targeted alpha-particle
      emitters hold great promise as therapeutic agents for disseminated disease.
      (225)Ac is a radionuclide generator that has a 10-d half-life and results in
      alpha-emitting daughter elements ((221)Fr, (217)At, (213)Bi) that lead to the
      emission of a total of 4 alpha-particles. The aim of this study was to develop
      approaches for stable and controlled targeting of (225)Ac to sites of
      disseminated tumor metastases. Liposomes with encapsulated (225)Ac were developed
      to retain the potentially toxic daughters at the tumor site. METHODS: (225)Ac was
      passively entrapped in liposomes. To experimentally test the retention of
      actinium and its daughters by the liposomes, the gamma-emissions of (213)Bi were
      measured in liposome fractions, which were separated from the parent liposome
      population and the free radionuclides, at different times. Under equilibrium
      conditions the decay rate of (213)Bi was used to determine the concentration of
      (225)Ac. Measurements of the kinetics of (213)Bi activity were performed to
      estimate the entrapment of (213)Bi, the last alpha-emitting daughter in the decay
      chain. RESULTS: Stable pegylated phosphatidylcholine-cholesterol liposomes of
      different sizes and charge were prepared. Multiple (more than 2) (225)Ac atoms
      were successfully entrapped per liposome. (225)Ac retention by zwitterionic
      liposomes was more than 88% over 30 d. Retention by cationic liposomes was lower.
      A theoretical calculation showed that for satisfactory (213)Bi retention (>50%),
      liposomes of relatively large sizes (>650 nm in diameter) are required. (213)Bi
      retention was experimentally verified to be liposome-size dependent. For large
      liposomes, the measured (213)Bi retention was lower than theoretically predicted
      (less than 10%). CONCLUSION: This work supports the hypothesis that it may be
      possible to develop (225)Ac-based therapies by delivering multiple (225)Ac atoms
      in liposomes. Improvements in the retention of (225)Ac daughters will likely be
      necessary to fulfill this potential. Because of the size of the liposomal
      structures required to contain the daughters, the approach is ideally suited for
      locoregional therapy (e.g., intraperitoneal, intrahepatic artery, or
      intrathecal).

PMID- 14960645
TI  - 99mTc-stannous colloid white cell scintigraphy in childhood inflammatory bowel
      disease.
AB  - 99mTc-Labeled white cell scintigraphy (WCS) has been used for the investigation
      of inflammatory bowel disease (IBD) in adults, but data on children are limited.
      The most common agent used is (99m) Tc-hexamethylpropyleneamine oxime (HMPAO);
      however, this agent has limitations. In a retrospective study, we assessed the
      use of (99m)Tc-stannous colloid WCS for the initial evaluation of children with
      suspected IBD. METHODS: Diagnostic, endoscopic, and contrast radiography results
      were retrospectively collected from the medical records. Two experienced nuclear
      physicians unaware of the patient data interpreted the WCS results, with
      agreement reached by consensus. Statistical analysis was performed on the ability
      of WCS to detect active disease and localize it topographically and on a
      comparison of diagnostic methods, using a combination of clinical features and
      endoscopy as the reference standard. RESULTS: Between 1996 and 1999, 64 patients
      (35 male and 29 female; mean age, 12.5 y; age range, 2-19 y) had WCS performed,
      with IBD subsequently diagnosed in 34 patients. (99m)Tc-Stannous colloid WCS had
      an 88% sensitivity, 90% specificity, and 8.8 likelihood ratio for initial
      investigation of IBD. Agreement was poor for topographic localization of disease.
      Small-bowel series had a 75% sensitivity, 50% specificity, and 1.5 likelihood
      ratio for detecting endoscopic disease of the terminal ileum and proximal colon.
      CONCLUSION: Our results confirm that WCS is a useful imaging technique for the
      initial evaluation of patients with suspected IBD. (99m)Tc-Stannous colloid had
      results at least comparable to those of other WCS agents, and in children,
      (99m)Tc-stannous colloid WCS should be preferred in view of lower cost, shorter
      preparation time, and the smaller blood volumes required.

PMID- 14960646
TI  - Normal and abnormal 18F-FDG endometrial and ovarian uptake in pre- and
      postmenopausal patients: assessment by PET/CT.
AB  - The purpose of the study was to assess physiologic endometrial (18)F-FDG uptake
      during the 4 phases of the menstrual cycle and to differentiate between
      physiologic and malignant endometrial uptake. METHODS: Endometrial (18)F-FDG
      uptake, expressed as standardized uptake value (SUV), was measured on PET/CT
      images of 285 consecutive female patients, of whom 246 (112 premenopausal and 134
      postmenopausal) had no known gynecologic malignancy and 39 (14 premenopausal and
      25 postmenopausal) had cervical, endometrial, or ovarian cancer. RESULTS: Two
      peaks of increased endometrial (18)F-FDG uptake were identified during the 4
      phase cycle. The mean SUVs were 5 +/- 3.2 and 3.7 +/- 0.9 in menstruating and
      ovulating patients, respectively, and 2.6 +/- 1.1 and 2.5 +/- 1.1 in patients in
      the proliferative and secretory phases, respectively. The mean endometrial SUV in
      postmenopausal patients not receiving hormonal therapy was 1.7 +/- 0.5.
      Oligomenorrhea and benign endometrial abnormalities were associated with
      increased (18)F-FDG uptake. Neither contraceptives nor hormonal therapy was
      associated with a significant increase in endometrial uptake. In addition to the
      increased tumor uptake measured in patients with cervical cancer (14.9 +/- 7.3 in
      postmenopausal patients and 12.2 +/- 6.6 in premenopausal patients), increased
      uptake was also found in the adjacent endometrium, although it appeared normal on
      CT (4.8 +/- 2 in premenopausal patients and 4.7 +/- 2.8 in postmenopausal
      patients). Increased ovarian (18)F-FDG uptake was detected in 7 patients with
      ovarian cancer (9.1 +/- 4) and in 21 premenopausal patients without known ovarian
      malignancy (5.7 +/- 1.5, P < 0.01), of whom 15 were at mid cycle and 3 reported
      oligomenorrhea. An ovarian SUV of 7.9 separated benign from malignant uptake with
      a sensitivity of 57% and a specificity of 95%. CONCLUSION: In premenopausal
      patients, normal endometrial uptake of (18)F-FDG changes cyclically, increasing
      during the ovulatory and menstrual phases. Increased uptake in the endometrium
      adjacent to a cervical tumor does not necessarily reflect endometrial tumor
      invasion. Increased ovarian uptake in postmenopausal patients is associated with
      malignancy, whereas increased ovarian uptake may be functional in premenopausal
      patients.

PMID- 14960647
TI  - Assessment of malignant skeletal disease: initial experience with 18F-fluoride
      PET/CT and comparison between 18F-fluoride PET and 18F-fluoride PET/CT.
AB  - 18F-fluoride PET/CT was performed on 44 oncologic patients to evaluate its
      diagnostic accuracy in assessing malignant osseous involvement and in
      differentiating malignant from benign bone lesions. METHODS: (18)F-fluoride PET
      and (18)F-fluoride PET/CT were interpreted separately. Lesions showing increased
      (18)F-fluoride uptake were categorized as malignant, benign, or inconclusive. The
      final diagnosis of lesions was based on histopathology, correlation with
      contemporaneous diagnostic CT or MRI, or clinical follow-up of at least 6 mo
      (mean, 10 +/- 3 mo). RESULTS: Increased (18)F-fluoride uptake was detected at 212
      sites, including 111 malignant lesions, 89 benign lesions, and 12 lesions for
      which the final diagnosis could not be determined. In a lesion-based analysis,
      the sensitivity of PET alone in differentiating benign from malignant bone
      lesions was 72% when inconclusive lesions were considered false negative and 90%
      when inconclusive lesions were considered true positive. On PET/CT, 94 of 111
      (85%) metastases presented as sites of increased uptake with corresponding lytic
      or sclerotic changes, and 16 of the 17 remaining metastases showed normal
      appearing bone on CT, for an overall sensitivity of 99% for tumor detection. For
      only 1 metastasis was PET/CT misleading, suggesting the false diagnosis of a
      benign lesion. The specificity of PET/CT was significantly higher than that of
      PET alone (97% vs. 72%, P < 0.001). PET/CT identified benign abnormalities at the
      location exactly corresponding to the scintigraphic increased uptake for 85 of 89
      (96%) benign lesions. In a patient-based analysis, the sensitivity of PET and
      PET/CT was 88% and 100%, respectively (P < 0.05) and the specificity was 56% and
      88%, respectively (not statistically significant). Among the 12 patients referred
      for (18)F-fluoride assessment because of bone pain despite negative findings on
      (99m)Tc-methylene diphosphonate bone scintigraphy, (18)F-fluoride PET/CT
      suggested malignant bone involvement in all 4 patients with proven skeletal
      metastases, a potential benign cause in 4 of 7 patients who had no evidence of
      metastatic disease, and a soft-tissue tumor mass invading a sacral foramen in 1
      patient. CONCLUSION: The results indicate that (18)F-fluoride PET/CT is both
      sensitive and specific for the detection of lytic and sclerotic malignant
      lesions. It accurately differentiated malignant from benign bone lesions and
      possibly assisted in identifying a potential cause for bone pain in oncologic
      patients. For most lesions, the anatomic data provided by the low-dose CT of the
      PET/CT study obviates the performance of full-dose diagnostic CT for correlation
      purposes.

PMID- 14960648
TI  - Malignant involvement of the spine: assessment by 18F-FDG PET/CT.
AB  - The purpose of the study was to assess the role of (18)F-FDG PET/CT in the
      assessment of secondary malignant involvement of the spinal column. METHODS: In
      51 patients, 242 lesions at the spinal region detected on (18)F-FDG PET/CT were
      interpreted separately on PET, CT, and fused PET/CT images, including
      differentiation between benign and malignant lesions and the level in the
      vertebral column. CT evaluation also included the type of bony lesion
      (osteolytic, osteoblastic, or mixed) and accompanying soft-tissue abnormalities;
      for example, epidural masses and tumor involvement of the neural foramina.
      RESULTS: Of the 242 lesions detected on PET/CT, PET alone identified 220 lesions
      and CT alone identified 159; 217 (90%) were malignant and 25 benign. (18)F-FDG
      PET alone detected significantly more malignant lesions than did CT alone (96%
      vs. 68%, respectively, P < 0.001). The specificity was 56% for both PET alone and
      CT alone. PET alone was incorrect in determining the level of abnormality within
      the vertebral column in 33 (15%) lesions and in determining the part of the
      vertebra involved in 40 (18%) lesions. In 17 (33%) patients, either epidural
      extension of tumor (n = 7 lesions), neural foramen involvement of tumor (n = 7
      lesions), or a combination of both (n = 11 lesions) was detected. On a patient
      based analysis, the sensitivity of PET and of PET/CT for the detection of spinal
      metastasis was 98% and 74%, respectively (P < 0.01). CONCLUSION: (18)F-FDG PET/CT
      has better specificity for detection of malignant involvement of the spine than
      does (18)F-FDG PET. It allows for precise localization of lesions and identifies
      accompanying soft-tissue involvement, which is of potential neurologic
      significance.

PMID- 14960649
TI  - Quantitative analysis of 99mTc-DMSA during acute pyelonephritis for prediction of
      long-term renal scarring.
AB  - This study was performed to evaluate a quantitative method based on (99m)Tc-DMSA
      renal planar scintigraphy performed during acute pyelonephritis (APN) to detect
      kidneys at risk of scarring. METHODS: A total of 43 children (5.8 +/- 3.6 y old
      [mean +/- SD]) were examined by (99m)Tc-DMSA scintigraphy during (DMSA 1) and 8
      +/- 2 mo after (DMSA 2) APN. Two levels of interpretation were performed
      independently: first, a semiquantitative analysis to classify the kidneys by
      considering the evolution between DMSA 1 and DMSA 2 (i.e., to determine which
      kidneys had developed scarring), and second, an automatic quantitative analysis
      of DMSA 1 to define and to evaluate a predictive index for kidney evolution from
      DMSA 1 to DMAS 2. The method consisted of determining an automatic threshold for
      the kidney and then calculating ratios of the count density in a given isocount
      n% (region of interest containing all the pixels with a value > or = n% of the
      value of the pixel with the maximal activity value) to the count density in a 20%
      isocount (C(n%)) and the number of pixels in a given isocount to the number of
      pixels in a 20% isocount (S(n%)). RESULTS: All kidneys normal at DMSA 1 remained
      normal at DMSA 2. For the automatic index, the C(70%) ratio was considered the
      best index for the prediction of scarring. When this C(70%) ratio was used, a
      cutoff value of 0.45 was able to predict scarring with a sensitivity of 0.83, a
      specificity of 0.78, a positive predictive value of 0.85, and a negative
      predictive value of 0.77. CONCLUSION: A cutoff value of 0.45 for the C(70%) ratio
      calculated for (99m)Tc-DMSA scintigraphy performed during APN may be useful for
      detecting kidneys at risk of scarring.

PMID- 14960650
TI  - Cardiac pacemakers and central venous lines can induce focal artifacts on CT
      corrected PET images.
AB  - PET/CT imaging can be associated with focal artifactual (18)F-FDG uptake
      introduced by metallic implants or contrast agents. It is unknown whether cardiac
      pacemakers or permanent central venous catheters can also result in such
      artifacts. METHODS: Twenty-seven patients with permanent central venous lines (13
      men and 14 women; mean age +/- SD, 53.8 +/- 16.2 y) and 9 patients with
      pacemakers (7 men and 2 women; mean age +/- SD, 74.8 +/- 5.1 y) who were referred
      for a variety of oncologic indications were studied with lutetium
      oxyorthosilicate-based dual-slice PET/CT after injection of 7.77 MBq/kg of (18)F
      FDG. CT-corrected and -uncorrected PET images were reviewed, and (18)F-FDG uptake
      was graded as absent, mild, moderate, or intense. RESULTS: CT-corrected PET
      images revealed focally increased uptake of moderate intensity in all patients
      with cardiac pacemakers and focally increased uptake of mild intensity in 8 of 27
      patients (29.6%) with central venous lines. CONCLUSION: Cardiac pacemakers and
      reservoirs of central venous lines can induce artifactual (18)F-FDG on CT
      corrected PET images. Thus, in patients with permanent central lines or
      pacemakers, both corrected and uncorrected PET images need to be reviewed to
      avoid false-positive PET findings.

PMID- 14960651
TI  - Uptake of 111In-Z2D3 on SPECT imaging in a swine model of coronary stent
      restenosis correlated with cell proliferation.
AB  - Small targets such as cell proliferation in the coronary arteries may potentially
      be detected with single-photon imaging using high-radiotracer-specific activity.
      We hypothesized that an antibody linked to polymers to increase specific
      radioactivity can be visualized on SPECT images and that counts in the target
      will correlate with the strength of the biologic signal. METHODS: Twenty-four
      stents were placed using the balloon overexpansion technique in the coronary
      arteries of 14 juvenile domestic swine. One week later, the animals received 74
      MBq of (111)In-diethylenetriaminepentaacetic acid-polylysine Z2D3-F(ab')(2), and
      SPECT imaging was performed at 24 h. The coronary vessels were removed, and the
      stented vessels were processed with plastic embedding and sectioning. Medial and
      neointimal areas, percentage of vessel stenosis, and cell proliferation indices
      were quantified using a 5-bromo-2-deoxyuridine (BrdU) labeling index.
      Reconstructed SPECT images were interpreted for tracer uptake in coronary
      vessels. RESULTS: Sixteen of the vessels were positive on SPECT imaging and 10
      were negative. The percentage injected dose was 0.85 +/- 0.28 x 10(-3) in scan
      positive vessels and 0.34 +/- 0.11 x 10(-3) in scan-negative vessels (P < 0.001).
      The medial-plus-neointimal proliferative index was 42 +/- 11 in scan-positive
      vessels and 11 +/- 11 in scan-negative vessels (P < 0.0001). The percentage
      stenoses were 21% +/- 22% versus 19% +/- 15% (not statistically significant).
      When individual values for the stented-to-control vessel counts were plotted
      against BrdU labeling index, a significant relationship was found (r(2) = 0.441;
      P = 0.0014). CONCLUSION: These data indicate that small targets relevant to human
      coronary vascular disease may be detected using polymer-modified radiolabeled
      antibodies.

PMID- 14960652
TI  - Can molecular imaging predict in-stent restenosis?

PMID- 14960653
TI  - Evaluation of 4-borono-2-18F-fluoro-L-phenylalanine-fructose as a probe for boron
      neutron capture therapy in a glioma-bearing rat model.
AB  - L-p-Boronophenylalanine (BPA) has been applied as a potential boron carrier for
      the treatment of malignant glioma in clinical boron neutron capture therapy
      (BNCT) since 1994. To provide the pharmacokinetics of BPA for clinical use of
      BNCT in Taiwan, 4-borono-2-(18)F-fluoro-L-phenylalanine-fructose ((18)F-FBPA-Fr)
      was synthesized and the biologic characteristics of this radiotracer in glioma
      bearing rats were investigated. METHODS: Radiolabeled (18)F-F(2) was produced via
      the (20)Ne(d,alpha)(18)F reaction, and (18)F-acetyl hypofluorite ((18)F-AcOF) was
      generated by passing (18)F-F(2) through a column filled with tightly packed
      KOAc/HOAc powder. The effluent containing (18)F-AcOF was bubbled into BPA in
      trifluoroacetic acid, then purified by high-performance liquid chromatography,
      and further composited with fructose to afford (18)F-FBPA-Fr. Male Fischer 344
      rats bearing F98 glioma in the left brain were used for biologic studies. The
      biodistribution of BPA-Fr and (18)F-FBPA-Fr was determined, and the
      microautoradiography and PET imaging of (18)F-FBPA-Fr were performed, on the 13th
      day after tumor inoculation. RESULTS: The radiochemical purity of (18)F-FBPA-Fr
      was >97% and the radiochemical yield of (18)F-FBPA-Fr was 20%-25%. In glioma
      bearing rats, the accumulation ratios of B-10 for glioma-to-normal brain were
      2.05, 1.86, 1.24, and 1.10 at 0.5, 1, 2, and 4 h, respectively, after
      administration of 43 mg BPA-Fr via the tail vein. The accumulation ratios of
      (18)F-FBPA-Fr for glioma-to-normal brain were 3.45, 3.13, 2.61, and 2.02, whereas
      the tumor-to-heart blood ratios were 1.72, 2.61, 2.00, and 1.93, respectively,
      for the same time points. The uptake characteristics of BPA-Fr and (18)F-FBPA-Fr
      in F98 glioma were similar with a maximum at 1 h after the drugs' administration.
      The results obtained from the biodistribution studies indicated that 0.5-1 h
      after BPA-Fr injection would be the optimal time for BNCT. Biodistribution, PET
      images, and brain microautoradiography of (18)F-FBPA-Fr all confirmed this
      finding. CONCLUSION: (18)F-FBPA-Fr showed specific tumor uptake in F98 glioma
      bearing rats and could be used as a probe for BPA-Fr in BNCT. This study provides
      useful information for the future clinical application of BNCT in brain tumor
      therapy.

PMID- 14960654
TI  - Feasibility of 99mTc-annexin V for repetitive detection of apoptotic tumor
      response to chemotherapy: an experimental study using a rat tumor model.
AB  - Annexin V (annexin A5), a human protein with a high affinity for
      phosphatidylserine, labeled with (99m)Tc can detect apoptosis in vivo. In the
      repetitive detection of apoptosis with (99m)Tc-annexin V, however, the specific
      binding of annexin V to phosphatidylserine might affect the subsequent detection
      of apoptosis with this compound. To determine whether there is interference with
      repetitive doses of annexin V, we evaluated the effects of previous
      administration of cold annexin V on accumulation of (99m)Tc-annexin V in tumors
      in an experimental tumor model. METHODS: Rats bearing hepatoma received
      cyclophosphamide (150 mg/kg, intraperitoneally) 11 d after the tumor inoculation.
      Cold annexin V (20 microg/kg, intravenously) was administered 24 h before or
      after the cyclophosphamide treatment (n = 7/group). (99m)Tc-Annexin V was
      injected intravenously (radioactive dose, 5-23 MBq/kg; mass dose, 20 microg/kg),
      and radioactivity in tissues was determined 6 h later. RESULTS: Accumulation of
      (99m)Tc-annexin V in tumors was not significantly affected by previous treatment
      with cold annexin V before or after chemotherapy. CONCLUSION: These results
      demonstrate the feasibility of (99m)Tc-annexin V imaging for repetitive detection
      of apoptosis, which is highly required in the clinical setting.

PMID- 14960655
TI  - Susceptibility of the human pathogenic fungi Cryptococcus neoformans and
      Histoplasma capsulatum to gamma-radiation versus radioimmunotherapy with alpha-
      and beta-emitting radioisotopes.
AB  - Fungal diseases are difficult to treat in immunosuppressed patients and,
      consequently, new approaches to therapy are urgently needed. One novel strategy
      is to use radioimmunotherapy (RIT) with fungal-binding monoclonal antibodies
      (mAbs) labeled with radionuclides. However, many fungi manifest extreme
      resistance to gamma-radiation, such that the doses of several thousand gray are
      required for 90% cell killing, whereas for mammalian cells the lethal dose is
      only a few gray. We compared the susceptibility of human pathogenic fungi
      Cryptococcus neoformans (CN) and Histoplasma capsulatum (HC) to external gamma
      radiation and to the organism-specific mAbs 18B7 and 9C7, respectively,
      conjugated to (213)Bi and (188)Re radionuclides. METHODS: CN and HC cells were
      irradiated with up to 8,000 Gy ((137)Cs source, 30 Gy/min). RIT of CN with
      (213)Bi- and (188)Re-labeled specific mAb and of HC with (188)Re-labeled specific
      mAb used 0-1.2 MBq per 10(5) microbial cells. After irradiation or RIT, the cells
      were plated for colony-forming units (CFUs). Cellular dosimetry calculations were
      performed, and the pathway of cell death after irradiation was evaluated by flow
      cytometry. RESULTS: Both CN and HC proved to be extremely resistant to gamma
      radiation such that significant killing was observed only for doses of >4,000 Gy.
      In contrast, these cells were much more susceptible to killing by radiation
      delivered with a specific mAb, such that a 2-logarithm reduction in colony
      numbers was achieved by incubating them with (213)Bi- and (188)Re-labeled mAb
      18B7 or with (188)Re-9C7 mAb. Dosimetry calculations showed that RIT was
      approximately 1,000-fold more efficient in killing CN and approximately 100-fold
      more efficient in killing HC than gamma-radiation. Both gamma-radiation and RIT
      caused cell death via an apoptotic-like pathway with a higher percentage of
      apoptosis observed in RIT-treated cells. CONCLUSION: Conjugating a radioactive
      isotope to a fungal-specific antibody converted an immunoglobulin with no
      antifungal activity into a microbicidal molecule. RIT of fungal cells using
      specific antibodies labeled with alpha- and beta-emitting radioisotopes was
      significantly more efficient in killing CN and HC than gamma-radiation when based
      on the mean absorbed dose to the cell. These results strongly support the concept
      of using RIT as an antimicrobial modality.

PMID- 14960656
TI  - 99mTc-Labeled UBI 29-41 peptide for monitoring the efficacy of antibacterial
      agents in mice infected with Staphylococcus aureus.
AB  - Based on our earlier observation that (99m)Tc-UBI 29-41, a radiolabeled peptide
      derived from ubiquicidin (UBI), discriminates between infections and sterile
      inflammatory processes, we considered the possibility that this tracer could be
      used for monitoring the efficacy of antibacterial agents in animals infected with
      Staphylococcus aureus. METHODS: We injected (99m)Tc-UBI 29-41 into S. aureus
      infected mice after treatment with various doses of cloxacillin or erythromycin.
      At intervals thereafter, accumulation of the radiolabeled peptide at the site of
      infection was assessed by scintigraphy. When S. aureus was antibiotic resistant,
      we evaluated the efficacy of hLF 1-11, an antimicrobial peptide derived from
      human lactoferrin (hLF), in rats using (99m)Tc-UBI 29-41 and scintigraphy.
      RESULTS: Decreasing amounts of radiolabeled peptide at the site of the S. aureus
      infection in animals correlated (r(2) > 0.81; P < 0.001) with increasing doses of
      cloxacillin in animals. An effective dose of erythromycin resulted in reduced (P
      = 0.023) accumulation of the radiolabeled peptide at the site of S. aureus
      infection in mice. In addition, we noted decreasing amounts of (99m)Tc-UBI 29-41
      at the site of infection after administration of increasing doses of hLF 1-11
      peptide in rats infected with antibiotic-resistant S. aureus. Furthermore, the
      number of viable bacteria decreased with increasing doses of cloxacillin or hLF 1
      11 peptide, and a good correlation (r(2) > 0.80; P < 0.001) between the
      accumulation of (99m)Tc-UBI 29-41 and the number of viable (antibiotic-resistant)
      S. aureus at the site of infection was seen. In an attempt to explain these
      results, we found that these antibacterial agents do not affect the in vitro
      binding of (99m)Tc-UBI 29-41 to bacteria. Furthermore, this radiolabeled peptide
      bound to free bacteria and to cell-adherent but not phagocytized S. aureus,
      suggesting that at sites of infection mainly extracellular bacteria are targeted
      by (99m)Tc-UBI 29-41. CONCLUSION: (99m)Tc-UBI 29-41 allows the monitoring of the
      efficacy of antibacterial agents in mice and rats with S. aureus infections.

PMID- 14960657
TI  - Optimization of radioimmunotherapy of renal cell carcinoma: labeling of
      monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re.
AB  - Radioimmunotherapy (RIT) can be performed with various radionuclides. We tested
      the stability, biodistribution, and therapeutic efficacy of various
      radioimmunoconjugates ((131)I, (88/90)Y, (177)Lu, and (186)Re) of chimeric
      antirenal cell cancer monoclonal antibody G250 (mAb cG250) in nude mice with
      subcutaneous renal cell cancer (RCC) tumors. METHODS: The (88/90)Y and (177)Lu
      labeling procedures of cG250 conjugated with cyclic diethylenetriaminepentaacetic
      acid anhydride (cDTPA), isothiocyanatobenzyl-DTPA (SCN-Bz-DTPA), or 1,4,7,10
      tetraazacyclododecanetetraacetic acid (DOTA) were characterized. Stability of the
      labeled conjugates in plasma at 37 degrees C was assessed. Biodistribution and
      therapeutic efficacy of labeled cG250 were compared in nude mice with SK-RC-52
      human RCC xenografts. RESULTS: Both SCN-Bz-DTPA and DOTA were stable in vitro
      (<5% release of the radiolabel during 14 and 21 d of incubation) and in vivo
      (uptake in bone </= 1.5 percentage injected dose per gram [%ID/g] at 7 d after
      injection) when used to label (88)Y or (177)Lu to cG250. The DOTA conjugate was
      slightly but significantly more stable than SCN-Bz-DTPA at 7 d after injection.
      In vivo, these cG250 preparations showed high tumor uptake (70 +/- 15 %ID/g +/-
      SD at 7 d after injection). Maximum tumor uptake for (125)I-cG250 and (186)Re
      mercaptoacetyltriglycine-(MAG3)-cG250 (<20 +/- 3 %ID/g +/- SD) was reached at 3 d
      after injection and was much lower in comparison with cG250 labeled with the
      residualizing radionuclides. Because the highest specific activities could be
      prepared using SCN-Bz-DTPA, and relatively low protein doses of cG250 could be
      administered without saturating the tumor, cG250-SCN-Bz-DTPA conjugates were used
      in RIT studies. In RIT experiments at maximum tolerated dose, tumor growth was
      delayed most effectively by cG250 labeled with (177)Lu, next most effectively by
      (90)Y and (186)Re (which were approximately equal), and least by (131)I (delayed
      by approximately 185, 125, 90, and 25 d, respectively). The best median survival
      (300 d) was observed for (177)Lu-SCN-Bz-DTPA-cG250. Median survival for control
      groups was <150 d. CONCLUSION: DOTA-conjugated radiolabeled antibodies were the
      most stable radioimmunoconjugates in vitro and in vivo as manifested by the
      lowest bone uptake. However, specific activity was higher for SCN-Bz-DTPA. The
      RIT studies clearly showed that the therapeutic efficacy of mAb cG250 labeled
      with (177)Lu, (90)Y, or (186)Re was superior to that of (131)I-cG250. The
      residualizing radionuclides (177)Lu and (90)Y led to higher radiation doses to
      the tumor and most likely are better candidates than conventionally radiolabeled
      (131)I for RIT with cG250 in patients with RCC.

PMID- 14960658
TI  - Quantitative analysis of (-)-N-(11)C-propyl-norapomorphine in vivo binding in
      nonhuman primates.
AB  - (-)-N-(11)C-propyl-norapomorphine ((11)C-NPA) is a new dopamine agonist PET
      radiotracer that holds potential for imaging the high-affinity states of dopamine
      D(2)-like receptors in the living brain. The goal of this study was to develop
      and evaluate analytic strategies to derive in vivo (11)C-NPA binding parameters.
      METHODS: Two baboons were scanned 4 times after (11)C-NPA injections. The
      metabolite-corrected arterial input functions were measured. Regional brain time
      activity curves were analyzed with kinetic and graphical analyses, using the
      arterial time-activity curve as the input function. Data were also analyzed with
      the simplified reference-tissue model (SRTM) and graphical analysis with
      reference-region input. RESULTS: (11)C-NPA exhibited moderately fast metabolism,
      with 31% +/- 5% of arterial plasma concentration corresponding to the parent
      compound at 40 min after injection. Plasma clearance was 29 +/- 1 L/h, and plasma
      free fraction (f(1)) was 5% +/- 1%. For kinetic analysis, a 1-tissue compartment
      model (1TCM) provided a good fit to the data and more robust derivations of the
      tissue distribution volumes (V(T), in mL/g) than a 2-tissue compartment model
      (2TCM). Using 1TCM, V(T)s in the cerebellum and striatum were 3.4 +/- 0.4 and 7.5
      +/- 2 mL/g, respectively, which led to estimates of striatal binding potential
      (BP) of 4.0 +/- 1.1 mL/g and striatal equilibrium specific-to-nonspecific
      partition coefficient (V(3)") of 1.2 +/- 0.2. V(T) values derived with graphical
      analysis were well correlated with but slightly lower than V(T) values derived
      with kinetic analysis. V(3)" values derived with SRTM were well correlated with
      but slightly higher than V(3)" values derived with kinetic analysis. Using any
      method, a significant difference was detected in BP and V(3)" values between the
      2 animals. It was determined that 30 min of scanning data were sufficient to
      derive V(3)" values using kinetic, graphical (arterial input and reference-region
      input), and SRTM analyses. CONCLUSION: This study indicates that (11)C-NPA is a
      suitable PET tracer to quantify the agonist high-affinity sites of D(2)-like
      receptors.

PMID- 14960659
TI  - 68Ga-labeled oligonucleotides for in vivo imaging with PET.
AB  - The biologic evaluation in living rats of (68)Ga-labeled oligonucleotides as
      imaging agents for PET is reported. METHODS: (68)Ga, a positron-emitting
      radionuclide (half-life, 68 min), along with a macrocyclic chelating agent,
      1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA), was used for
      labeling of antisense oligonucleotides targeting activated human K-ras oncogene.
      The biologic properties of 3 different forms of the oligonucleotides-that is, 2'
      deoxyphosphodiester (PO), 2'-deoxyphosphorothioate (PS), and 2'-O-methyl
      phosphodiester (OMe)-were studied first. The biodistribution and biokinetics were
      evaluated in vivo in athymic rats, each bearing a tumor of A549 cells, containing
      K-ras point mutation in codon 12, and a tumor of BxPC-3 cells, containing wild
      type K-ras. Dynamic PET imaging lasting up to 2 h was performed immediately after
      intravenous injection of (68)Ga-oligonucleotide. Blank studies were performed
      using (68)GaCl(3) or (68)Ga-DOTA alone without oligonucleotide. The (68)Ga
      antisense oligonucleotide uptake in tumors was also compared with the (18)F-FDG
      and (68)Ga-sense oligonucleotide uptakes. In addition, oligonucleotide binding to
      human plasma proteins and to human albumin was examined by means of
      ultrafiltration. RESULTS: The oligonucleotides can be stably labeled with (68)Ga
      and DOTA chelate. Intravenously injected (68)Ga-oligonucleotides of 17-mer length
      revealed high-quality PET images, allowing quantification of the biokinetics in
      major organs and in tumors. The biodistribution and biokinetics of intravenously
      administered (68)Ga-oligonucleotide varied considerably with the nature of the
      oligonucleotide backbone. CONCLUSION: We conclude that (68)Ga labeling of
      oligonucleotides is a convenient approach for in vivo imaging and quantification
      of oligonucleotide biokinetics in living animals with PET.

PMID- 14960660
TI  - A specific chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6
      dihydropyrimidine-1-yl)-N-[[3,4-dioxo-1-phenyl-7-(2-pyridyloxy)]-2
      heptyl]acetamide (NK3201), suppresses development of abdominal aortic aneurysm in
      hamsters.
AB  - In this study, we investigated the effect of a specific chymase inhibitor, 2-(5
      formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[[3,4-dioxo-1-phenyl-7
      (2-pyridyloxy)]-2-heptyl]acetamide (NK3201), in the development of abdominal
      aortic aneurysm in a hamster experimental model. The abdominal aortic aneurysm
      was induced by application of elastase onto the abdominal aorta in hamster. Each
      hamster was administered NK3201 (30 mg/kg/day p.o.) or placebo beginning 4 days
      before application of elastase and continuing through the experiments. Sham
      operated hamsters received saline application onto the abdominal aorta. Two weeks
      after application of elastase, the aortic diameter in the placebo-treated group
      was significantly increased to 1.6-fold compared with the value for the sham
      operated group, whereas that in the NK3201-treated group was significantly
      reduced. The chymase activities in the sham-operated and the placebo-treated
      groups were 0.35 +/- 0.01 and 3.44 +/- 0.62 mU/mg protein, respectively, and this
      difference was significant. NK3201 significantly reduced the chymase activity in
      the placebo-treated group. Here, we demonstrated for the first time that a
      chymase inhibitor prevented the development of abdominal aortic aneurysm in a
      hamster experimental model.

PMID- 14960661
TI  - Coadministration of a liver X receptor agonist and a peroxisome proliferator
      activator receptor-alpha agonist in Mice: effects of nuclear receptor interplay
      on high-density lipoprotein and triglyceride metabolism in vivo.
AB  - Liver X receptors (LXRs) are master transcription factors regulating cholesterol
      and fatty acid metabolism. Treatment of C57B6 mice with a specific synthetic LXR
      agonist, N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy
      1(trifluoromethyl)-ethyl]phenyl]-benzenesulfonamide (T0901317), resulted in
      elevated high-density lipoprotein (HDL) cholesterol as well as plasma and liver
      triglycerides. Peroxisome proliferator-activated receptor-alpha (PPARalpha)
      agonists are known to induce peroxisomal fatty acid beta-oxidation and also
      mediate HDL cholesterol metabolism. We have explored the hypothesis that
      simultaneous activation of PPARalpha and LXR may lead to additive effects on HDL
      cholesterol elevation as well as attenuation of triglyceride accumulation.
      Coadministration of T0901317 and the specific PPARalpha agonist [4-chloro-6-(2,3
      xylidino)-2-pyrimidinylthioacetic acid (Wy14643)] in mice led to synergistic
      elevation of HDL cholesterol that was primarily associated with enlarged HDL
      particles enriched with apoE and apoAI. Liver phospholipid transfer protein
      (PLTP) mRNA and plasma PLTP activity were additively elevated, suggesting a role
      of PLTP in the observed HDL cholesterol elevation. Moderate increases in plasma
      triglyceride levels induced by LXR activation was reduced, whereas the
      accumulation of triglyceride in the liver was not altered upon coadministration
      of the PPARalpha agonist. Peroxisomal fatty acid beta-oxidation in the liver was
      dramatically elevated upon PPARalpha activation as expected. Interestingly,
      activation of LXRs via T0901317 also led to a significant increase in peroxisomal
      fatty acid beta-oxidation. Sterol regulatory element binding protein 1c
      expression was dramatically up-regulated by the LXR agonist but was not changed
      with PPARalpha agonist treatment. Liver lipoprotein lipase expression was
      additively increased upon LXR agonist and PPARalpha agonist coadministration. Our
      studies mark the first exploration of nuclear receptor interplay on lipid
      homeostasis in vivo.

PMID- 14960662
TI  - Prodrug modification increases potassium tricyclo[5.2.1.0(2,6)]-decan-8-yl
      dithiocarbonate (D609) chemical stability and cytotoxicity against U937 leukemia
      cells.
AB  - Potassium tricyclo[5.2.1.0(2,6)]-decan-8-yl dithiocarbonate (D609) is a selective
      antitumor agent, potent antioxidant, and cytoprotectant. It has the potential to
      be developed as a unique chemotherapeutic agent that may provide dual therapeutic
      benefits against cancer, e.g., enhancing tumor cell death while protecting normal
      tissues from damage. However, D609 contains a dithiocarbonate (xanthate) group [O
      C(=S)S(-)/O-C(=S)SH], which is chemically unstable, being readily oxidized to
      form a disulfide bond with subsequent loss of all biological activities.
      Therefore, we developed the synthesis of a series of S-(alkoxyacyl) D609 prodrugs
      by connecting the xanthate group of D609 to an ester via a self-immolative
      methyleneoxyl group. These S-(alkoxylacyl)-D609 prodrugs are designed to release
      D609 in two steps: esterase-catalyzed hydrolysis of the acyl ester bond followed
      by conversion of the resulting hydroxymethyl D609 to formaldehyde and D609. Three
      S-(alkoxyacyl) D609 prodrugs were synthesized by varying the steric bulkiness of
      the acyl group. These prodrugs are stable to ambient conditions, but readily
      hydrolyzed by esterases to liberate D609 in a controlled manner. More
      importantly, the lead prodrug methyleneoxybutyryl D609 is biologically more
      effective than D609 in inhibiting sphingomyelin synthase, thereby increasing the
      level of ceramide and inducing apoptosis in U937 leukemia cells. The prodrug has
      a significantly lower LD(50) value than that of D609 (56.6 versus 117 microM)
      against U937 cells. These findings demonstrate that prodrug modification of the
      xanthate moiety with an alkoxyacyl group can improve D609 oxidative stability and
      enhance its antitumor activity.

PMID- 14960663
TI  - Ligament reconstruction with or without tendon interposition to treat primary
      thumb carpometacarpal osteoarthritis. A prospective randomized study.
AB  - BACKGROUND: Trapezial excision with ligament reconstruction and trapezial
      excision with ligament reconstruction combined with tendon interposition have
      proven to be highly effective techniques for treating primary osteoarthritis of
      the thumb carpometacarpal joint. To determine whether tendon interposition and
      proximal migration of the thumb metacarpal affect the objective and subjective
      outcomes, we compared the long-term outcomes of these two procedures performed in
      similar patient groups. METHODS: Forty-three patients (fifty-two thumbs) were
      randomized to undergo either trapezial excision with ligament reconstruction or
      the same procedure combined with tendon interposition. Fifteen patients treated
      with ligament reconstruction (group I) and sixteen patients treated with the same
      procedure with concomitant tendon interposition (group II) were evaluated after a
      mean follow-up period of 48.2 months. The outcomes were assessed with the Buck
      Gramcko score, with the total score calculated on the basis of the objective and
      subjective results. The ability to perform activities requiring use of the thumb
      and to return to work was analyzed as well. Radiographs were evaluated to
      determine the amount of proximal metacarpal migration at rest and under stress.
      RESULTS: Postoperatively, the mean total Buck-Gramcko score was rated as
      excellent in group I and as good in group II (p = 0.036). Group I had
      significantly better mean scores for palmar and radial abduction, cosmetic
      appearance, and willingness to undergo the surgery again under similar
      circumstances (p < 0.05). The mean scores for tip-pinch strength and the mean
      subjective scores for pain, strength, daily function, dexterity, and overall
      satisfaction did not differ significantly between the groups. Both groups had
      satisfactory results with regard to their performance of activities of daily
      living and their ability to return to work. With the numbers available, the
      amount of proximal metacarpal migration, at rest and under stress, did not differ
      significantly between the groups. CONCLUSIONS: Tendon interposition does not
      affect the outcome after the ligament reconstruction for the treatment of
      osteoarthritis of the thumb carpometacarpal joint. Furthermore, proximal
      migration of the thumb metacarpal does not appear to influence the functional
      outcome.

PMID- 14960664
TI  - The outcome and repair integrity of completely arthroscopically repaired large
      and massive rotator cuff tears.
AB  - BACKGROUND: The impact of a recurrent defect on the outcome after rotator cuff
      repair has been controversial. The purpose of this study was to evaluate the
      functional and anatomic results after arthroscopic repair of large and massive
      rotator cuff tears with use of ultrasound as an imaging modality to determine the
      postoperative integrity of the repair. METHODS: Eighteen patients who had
      complete arthroscopic repair of a tear measuring >2 cm in the transverse
      dimension were evaluated at a minimum of twelve months after surgery and again at
      two years after surgery. The evaluation consisted of a standardized history and
      physical examination as well as calculation of the preoperative and postoperative
      shoulder scores according to the system of the American Shoulder and Elbow
      Surgeons. The strength of both shoulders was quantitated postoperatively with use
      of a portable dynamometer. Ultrasound studies were performed with use of an
      established and validated protocol at a minimum of twelve months after surgery.
      RESULTS: Recurrent tears were seen in seventeen of the eighteen patients. Despite
      the absence of healing at twelve months after surgery, thirteen patients had an
      American Shoulder and Elbow Surgeons score of >/=90 points. Sixteen patients had
      an improvement in the functional outcome score, which increased from an average
      of 48.3 to 84.6 points. Sixteen patients had a decrease in pain, and twelve had
      no pain. Although eight patients had preoperative forward elevation to <95
      degrees, all eighteen regained motion above shoulder level and had an average of
      152 degrees of elevation. At the second evaluation, a minimum of twenty-four
      months after surgery, the average score, according to the system of the American
      Shoulder and Elbow Surgeons, had decreased to 79.9 points; only nine patients had
      a score of >/=90 points, and six patients had a score of </=79 points. The
      average forward elevation decreased to 142 degrees. CONCLUSIONS: Arthroscopic
      repair of large and massive rotator cuff tears led to a high percentage of
      recurrent defects. The minimum twelve-month evaluation showed excellent pain
      relief and improvement in the ability to perform activities of daily living
      despite the high rate of recurrent defects; however, at a minimum follow-up of
      two years, the results deteriorated with only twelve patients who had an American
      Shoulder and Elbow Surgeons score of >/=80.

PMID- 14960665
TI  - Anterior cruciate ligament reconstruction with a four-strand hamstring tendon
      autograft.
AB  - BACKGROUND: In this study, we analyzed the clinical outcomes at a minimum of two
      years following reconstruction of the anterior cruciate ligament with use of a
      four-strand hamstring tendon autograft in patients who had presented with a
      symptomatic torn anterior cruciate ligament. METHODS: One hundred and twenty-two
      consecutive patients who had an isolated, symptomatic anterior tibial subluxation
      associated with rupture of the anterior cruciate ligament were treated with
      reconstruction of the anterior cruciate ligament with a four-strand autologous
      semitendinosus-gracilis tendon graft. One surgeon performed all of the
      operations. Prior to surgery and at the follow-up examination, physical findings
      and functional scores were recorded and knee radiographs were analyzed. Following
      surgery, a six-month rehabilitation regimen was implemented. RESULTS: Eighty-five
      patients (70%) were available for follow-up, which included physical examination,
      scoring of function, KT-1000 arthrometric testing, and radiographs, at a mean of
      twenty-eight months. Seventy-six (89%) of the patients had negative Lachman and
      pivot shift tests. The mean Lysholm score improved from 55 points preoperatively
      to 91 points at the time of follow-up (p < 0.01). The mean Tegner score improved
      from 5 to 6 points (p < 0.01). Sixty-five patients had <3 mm of knee translation
      on arthrometric testing, but six patients with marked laxity were not tested.
      Three patients (4%) had a positive pivot shift test but had no history of
      additional trauma to the knee. Six patients (7%) had a traumatic rupture of the
      graft, occurring at a mean of 10.7 months postoperatively. Assessment of the
      follow-up radiographs demonstrated no evidence of progressive degenerative change
      compared with the appearance on the preoperative radiographs. However, tunnel
      expansion was noted in all patients. The tibial tunnel expanded a mean of 17%
      (range, 0% to 32%), and the femoral tunnel expanded a mean of 29% (range, 0% to
      40%). CONCLUSIONS: Reconstruction of the anterior cruciate ligament with use of a
      four-strand hamstring tendon autograft eliminated anterior tibial subluxation in
      89% of patients who were examined at a minimum of two years postoperatively. The
      overall rate of failure was 11%. The functional knee scores were significantly
      increased at the time of follow-up, but these results did not correlate with the
      results of knee arthrometric testing.

PMID- 14960666
TI  - Debridement arthroplasty for primary osteoarthritis of the elbow.
AB  - BACKGROUND: Formal and more aggressive debridement procedures have been described
      for the treatment of advanced primary osteoarthritis of the elbow. However, the
      literature contains little information on the results of long-term follow-up. The
      purpose of this study was to evaluate outcomes at an average of ten years after
      debridement arthroplasties performed through a posteromedial approach. METHODS:
      Thirty-three elbows with primary osteoarthritis in thirty-two patients treated
      with debridement arthroplasty were available for clinical follow-up evaluation.
      Through a posteromedial approach, the flexor-pronator muscle origin was reflected
      from the medial epicondyle and the joint was opened, preserving the anterior
      oblique bundle of the medial collateral ligament. The ulnar nerve was
      decompressed in all patients. Osteophytes were removed from the anterior, medial,
      and posterior sides of the elbow joint. In nine elbows, osteophytes from the
      lateral compartment were removed through an additional lateral approach. The mean
      age at the time of the operation was fifty years. The mean duration of follow-up
      was 121 months, and nineteen elbows were followed for more than ten years.
      RESULTS: The mean preoperative limitation of extension of 31 degrees was reduced
      to 24 degrees, and the mean preoperative flexion of 101 degrees improved to 118
      degrees (p < 0.001). The mean arc of movement improved by 24 degrees. The mean
      Japanese Orthopaedic Association elbow score was 83 points at the latest follow
      up evaluation compared with 60 points preoperatively (p < 0.001). Of twenty-five
      patients who had performed heavy manual work, nineteen (76%) returned to their
      previous job or an equivalent job. At the latest examination of the nineteen
      elbows followed for more than ten years, the limitation of extension was found to
      have increased by 7 degrees compared with the limitation noted at one year (p <
      0.009); the mean arc of flexion had remained the same. Three elbows required a
      reoperation. Overall, 85% of the elbows were satisfactory to the patients.
      CONCLUSIONS: Debridement arthroplasty through a posteromedial approach can
      provide stable and reliable long-term results with regard to relief of pain,
      gains in range of motion, and the patient's ability to return to his or her
      previous occupation. In our series, a modest loss of extension was observed at
      ten years, whereas the arc of flexion remained consistent.

PMID- 14960667
TI  - Total hip arthroplasty for congenital hip disease.
AB  - BACKGROUND: It is generally agreed that the clinical and radiographic results of
      total hip replacement performed for degenerative arthritis secondary to
      congenital hip disease vary depending on the severity of the anatomical
      abnormality. In this study, we report the mid-term and long-term clinical and
      radiographic results of total hip arthroplasty performed for each of the three
      different types of congenital hip disease. METHODS: Between 1976 and 1994, the
      senior author performed 229 consecutive primary total hip arthroplasties in 168
      patients with osteoarthritis secondary to congenital hip disease. Seventy-six
      hips were dysplastic, sixty-nine had a low dislocation, and eighty-four had a
      high dislocation. The Charnley low-friction technique was performed in 178 hips,
      and the so-called hybrid technique was performed in forty-six hips. Cementless
      arthroplasty was used in only five hips. RESULTS: After a minimum of seven years
      of follow-up, the rates of revision of the acetabular components were 15% in the
      dysplastic hips, 21% in the hips with a low dislocation, and 14% in those with a
      high dislocation. The rates of revision of the femoral components were 14%, 14%,
      and 16%, respectively. Survivorship analysis predicted an overall rate of
      prosthetic survival at fifteen years of 88.8% +/- 4.8% in the dysplastic hips,
      73.9% +/- 7.2% in the hips with a low dislocation, and 76.4% +/- 8.1% in those
      with a high dislocation. CONCLUSIONS: An understanding of the anatomical
      abnormalities and the use of appropriate techniques and implants make total hip
      arthroplasty feasible for treatment of the three types of congenital hip disease.
      In patients with a low dislocation, the major technical problem is reconstruction
      of the natural acetabulum. In those with a high dislocation, the challenge is to
      place the acetabular component inside the reconstructed true acetabulum and to
      use an appropriate femoral implant in the hypoplastic narrow femoral diaphysis.

PMID- 14960668
TI  - Accurate identification of adverse outcomes after cervical spine surgery.
AB  - BACKGROUND: Retrospective clinical studies frequently utilize surgeon records as
      a source of outcomes data. The accuracy of data derived from surgeon records,
      however, is unknown. The purpose of the present study was to evaluate the
      accuracy of surgeon records in documenting the prevalence of subjective adverse
      outcomes. METHODS: Consecutive patients who had undergone anterior cervical
      arthrodesis by four spine surgeons during a ten-month period were included.
      Surgeon records from the routine six-week, three-month, and six-month
      postoperative visits were examined for documentation of persistent dysphagia and
      dysphonia. Patients completed surveys inquiring about the presence and magnitude
      of symptoms at these three time-points. Agreement between the surgeon records and
      the patient surveys was analyzed with use of the kappa coefficient. RESULTS: One
      hundred and sixty-six patients had 342 postoperative visits. Dysphagia was
      documented twenty-six times in the surgeon records, compared with 107 times on
      the patient surveys. Dysphagia was thus underreported in 80% of cases. Similarly,
      dysphonia was documented ten times in the surgeon records, compared with seventy
      two times on the patient surveys. Poor correlation between the surgeon records
      and the patient surveys was observed regardless of symptom severity, previous
      anterior cervical surgery, anterior arthrodesis of three motion segments or more,
      arthrodesis cephalad to the fifth cervical level, and anterior cervical plate
      use. Poor correlation between the surgeon records and the patient surveys also
      was observed for each surgeon, regardless of subspecialty or institution.
      CONCLUSIONS: Correlation between the surgeon records and the patient surveys was
      consistently poor, regardless of the specific patient and surgeon factor
      analyzed. While we chose to study dysphonia and dysphagia, it is conceivable that
      the results may be generalizable to many situations in which office notes are
      utilized to ascertain the prevalence of subjective adverse outcomes. These
      results suggest that the prevalence of such outcomes may be seriously
      underreported in studies that rely on the retrospective analysis of surgeon
      records.

PMID- 14960669
TI  - Cementless acetabular fixation at fifteen years. A comparison with the same
      surgeon's results following acetabular fixation with cement.
AB  - BACKGROUND: Loosening of the acetabular component is the major long-term problem
      associated with total hip arthroplasty with cement. The purpose of the present
      study was to evaluate the minimum thirteen-year results associated with
      cementless acetabular components that had been inserted by a single surgeon and
      to compare them with the results associated with cemented acetabular components
      that had been inserted by the same surgeon. METHODS: One hundred and twenty
      consecutive, nonselected primary total hip replacements were performed in 108
      patients with use of a Harris-Galante-I cementless acetabular component and a
      cemented femoral component with a 28-mm head. The patients were evaluated
      clinically with use of a standard terminology questionnaire, and they were
      evaluated radiographically for loosening, component migration, wear, and
      osteolysis. The rates of revision for aseptic loosening and radiographic evidence
      of loosening for this cohort were compared with the rates for four previously
      reviewed consecutive series of hips in which the acetabular component had been
      inserted with cement. All patients were managed by the same surgeon, were
      followed for thirteen to fifteen years, and were evaluated with use of the same
      two criteria (revision and loosening) as the end points for Kaplan-Meier
      analysis. RESULTS: Sixty-six patients (seventy-two hips) were living and forty
      two patients (forty-eight hips) had died after thirteen to fifteen years of
      follow-up. No acetabular component had been revised because of aseptic loosening,
      and no acetabular component had migrated. With revision of the acetabular
      component for any reason as the end point, the survival rate was 81% +/- 8% at
      fifteen years. With revision of the acetabular component for clinical failure
      (osteolysis, wear, loosening, or dislocation) as the end point, the survival rate
      was 94% +/- 8% at fifteen years. Among the seventy hips with at least thirteen
      years of radiographic follow-up, five had pelvic osteolysis and three had had
      revision of a well-fixed acetabular component because of pelvic osteolysis
      secondary to polyethylene wear. The mean linear wear rate was 0.15 mm/yr (0.12
      mm/yr when one outlier was excluded). CONCLUSIONS: In terms of fixation, Harris
      Galante-I cementless acetabular components performed better than did cemented 22
      mm-inner-diameter Charnley acetabular components as well as 28-mm-inner-diameter
      all-polyethylene and metal-backed acetabular components that had been inserted by
      the same surgeon. However, the rate of wear was greater in association with the
      Harris-Galante-I cementless components than it was in association with the
      Charnley cemented all-polyethylene components.

PMID- 14960670
TI  - Surgical management of knee dislocations.
AB  - BACKGROUND: The evaluation and management of knee dislocations remain variable
      and controversial. The purpose of this study was to describe our method of
      surgical treatment of knee dislocations with use of a standardized protocol and
      to report the clinical results. METHODS: Forty-seven consecutive patients
      presented with an occult (reduced) or grossly dislocated knee. Fourteen of these
      patients were not included in this series because of confounding variables: four
      had an open knee dislocation, five had vascular injury requiring repair, three
      were treated with external fixation, and two had associated injury. The remaining
      thirty-three patients underwent surgical treatment for the knee dislocation with
      our standard approach. Anatomical repair and/or replacement was performed with
      fresh-frozen allograft tissue. Thirty-one of the thirty-three patients returned
      for subjective and objective evaluation with use of four different knee rating
      scales at a minimum of twenty-four months after the operation. RESULTS: Nineteen
      of the thirty-one patients were treated acutely (less than three weeks after the
      injury) and twelve, chronically. The mean Lysholm score was 91 points for the
      acutely reconstructed knees and 80 points for the chronically reconstructed
      knees. The Knee Outcome Survey Activities of Daily Living scores averaged 91
      points for the acutely reconstructed knees and 84 points for the chronically
      reconstructed knees. The Knee Outcome Survey Sports Activity scores averaged 89
      points for the acutely reconstructed knees and 69 points for the chronically
      reconstructed knees. According to the Meyers ratings, twenty-three patients had
      an excellent or good score and eight had a fair or poor score. Sixteen of the
      nineteen acutely reconstructed knees and seven of the twelve chronically
      reconstructed knees were given an excellent or a good Meyers score. The average
      loss of extension was 1 degrees, and the average loss of flexion was 12 degrees.
      There was no difference in the range of motion between the acutely and
      chronically treated patients. Four acutely reconstructed knees required
      manipulation because of loss of flexion. Laxity tests demonstrated consistently
      improved stability in all patients, with more predictable results in the acutely
      treated patients. CONCLUSIONS: Surgical treatment of the knee dislocations in our
      series provided satisfactory subjective and objective outcomes at two to six
      years postoperatively. The patients who were treated acutely had higher
      subjective scores and better objective restoration of knee stability than did
      patients treated three weeks or more after the injury. Nearly all patients were
      able to perform daily activities with few problems. However, the ability of
      patients to return to high-demand sports and strenuous manual labor was less
      predictable.

PMID- 14960671
TI  - Management of Mason type-III radial head fractures with a titanium prosthesis,
      ligament repair, and early mobilization.
AB  - BACKGROUND: Radial head fractures often occur in association with other elbow
      fractures and soft-tissue injuries. Radial head replacement is indicated for
      irreparable radial head fractures associated with elbow instability. The purpose
      of this study was to analyze the results after treatment of such injuries with a
      titanium radial head prosthesis, repair of torn collateral ligaments, and early
      mobilization of the elbow. METHODS: Sixteen patients with sixteen Mason type-III
      radial head fractures and collateral ligament injury were treated with use of a
      titanium radial head prosthesis over a five-year period at the Royal Adelaide
      Hospital and Modbury Public Hospital in South Australia. The surgery was
      performed acutely in ten patients and was delayed an average of thirty-seven days
      (range, fifteen to seventy-nine days) in six. All patients were followed
      clinically and radiographically for a mean of 2.8 years (range, 1.2 to 4.3
      years). RESULTS: Eight patients had an excellent result; five, a good result; and
      three, a fair result, according to the Mayo Elbow Performance Score. The three
      fair results occurred in patients with delayed surgery. The mean flexion
      contracture was 15 degrees (range, 0 degrees to 42 degrees ), with an average
      loss of 10 degrees (range, 0 degrees to 25 degrees ) of full flexion compared
      with that of the contralateral elbow. Both pronation and supination decreased an
      average of 12 degrees (range, 0 degrees to 45 degrees ) compared with that of the
      contralateral forearm. CONCLUSIONS: The results of treatment of Mason type-III
      radial head fractures with a monoblock titanium radial head prosthesis and soft
      tissue reconstruction are satisfactory. Early mobilization of the elbow is
      important for the restoration of elbow range of motion and function.

PMID- 14960672
TI  - Survival of microvascular physeal allograft transplants following withdrawal of
      short-term postoperative immunosuppression.
AB  - BACKGROUND: Physeal necrosis following vascularized allograft transplantation
      occurs because of vascular rejection. The effect of immunosuppression withdrawal
      on physeal viability after bone-healing to the recipient site was investigated
      with use of a validated model for heterotopic microvascular transplantation of
      rabbit tibial physeal allografts. Our hypothesis was that an allograft survives
      after withdrawal of immunosuppression only if bone-healing, and therefore
      epiphyseal and metaphyseal vascular continuity, occurs between the transplanted
      physis and the recipient bone. METHODS: Physeal grafts with adjacent exposed
      epiphyseal and metaphyseal bone were transplanted to allogeneic recipients. Graft
      circulation was restored microsurgically. The immunosuppression regimen consisted
      of cyclosporine, administered for six weeks, followed by withdrawal of
      immunosuppression for four weeks. The animals were killed at ten weeks
      postoperatively. Group I consisted of twelve allografts that were transferred
      with bone contact between the transplanted graft and the iliac crest recipient
      site, whereas group II consisted of twelve allografts transplanted without bone
      contact. Control groups had identical surgical procedures without
      immunosuppression. Longitudinal growth was assessed by fine-detail radiography,
      and osseous union was evaluated histologically. Transplanted physes were
      evaluated histologically, and cellular viability was quantified by
      bromodeoxyuridine uptake. Two-way analysis of variance was used to compare
      physeal viability between groups. RESULTS: Following immunosuppression
      withdrawal, the physeal grafts with bone contact had significantly greater
      viability indices (16.0 +/- 2.9 compared with 0.0 +/- 0.0, p < 0.005) and
      decreased longitudinal growth (5.1 +/- 1.9 mm compared with 10.3 +/- 3.5 mm, p <
      0.05), and they demonstrated histological features that were consistent with
      continued viability associated with mild rejection compared with grafts
      transplanted without bone contact. Abnormalities of physeal architecture,
      however, were seen routinely. All control physes transferred without
      immunosuppression were nonviable and did not grow. CONCLUSIONS: The viability of
      physeal allograft transplants is preserved following the withdrawal of
      immunosuppression, provided that the graft design and recipient site preparation
      allow for epiphyseal and metaphyseal neovascularization mediated by bone-healing
      between graft and recipient.

PMID- 14960673
TI  - The incidence of fractures and dislocations referred for orthopaedic services in
      a capitated population.
AB  - BACKGROUND: The purpose of this study was to determine the annual incidence rates
      of non-work-related traumatic fractures and dislocations (excluding head and
      facial injuries) referred for orthopaedic services in a large population enrolled
      under a capitated insurance contract. METHODS: The number of fractures and
      dislocations that were referred for orthopaedic services were recorded
      prospectively from among an average of 135,333 persons per year who were enrolled
      under a capitated insurance contract during the three-year study period. These
      data were used to determine the gender-specific and age-specific incidence rates
      of fractures and dislocations referred for orthopaedic services. RESULTS: A total
      of 3440 fractures and 422 dislocations were referred for orthopaedic services
      during the three-year study period. The incidence rate of fractures referred for
      orthopaedic services was 8.47 per 1000 member-years, with a significantly (p <
      0.0001) higher rate among males. Members between the ages of ten and fourteen
      years had the highest rate of fractures referred for orthopaedic services (21.52
      per 1000 member-years). The lifetime risk of a traumatic fracture referred for
      orthopaedic services to the age of sixty-five years was one in two for both males
      and females. The incidence rate of dislocations referred for orthopaedic services
      was 1.04 per 1000 member-years, which did not differ significantly (p = 0.75)
      between genders. Members between the ages of fifteen and nineteen years had the
      highest rate of dislocations referred for orthopaedic services (2.75 per 1000
      member-years). The lifetime risk of a traumatic dislocation referred for
      orthopaedic services to the age of sixty-five years was one in sixteen for both
      male and female members. CONCLUSIONS: Young males had the highest rate of
      traumatic fractures referred for orthopaedic services. Adolescents of both
      genders had high rates of traumatic dislocations referred for orthopaedic
      services. The lifetime risk of a non-work-related fracture referred for
      orthopaedic services to the age of sixty-five years is approximately equal to
      that of coronary artery disease.

PMID- 14960674
TI  - Total hip arthroplasty in patients with dwarfism.
AB  - BACKGROUND: Patients with short stature and osseous deformities resulting from
      osteochondrodysplasia frequently have premature development of advanced
      degenerative disease of the hip and thus may require total hip arthroplasty. The
      outcome of total hip arthroplasty in this group of young patients is unknown. In
      this study, we evaluated the long-term clinical and radiographic outcomes of
      total hip arthroplasty in patients with osteochondrodysplasia. METHODS: Between
      1971 and 1997, sixty-two total hip arthroplasties were performed at our
      institution in thirty-seven patients with severe osteoarthritis secondary to
      osteochondrodysplasia. There were seventeen female patients and twenty male
      patients. Their average height was 142 cm, and their average age at the time of
      the index arthroplasty was thirty-seven years. The patients were followed
      clinically with use of the Harris hip score for a mean of 12.8 years, and they
      were followed radiographically for a mean of 11.5 years. RESULTS: The mean Harris
      hip score improved significantly (p < 0.0001), from 57 points preoperatively to
      87 points at the time of the latest follow-up. Of the sixty hips available for
      follow-up, eighteen (30%) had required revision arthroplasty: fourteen required
      it because of aseptic loosening of one or both components; two, because of deep
      infection; one, because of periprosthetic fracture; and one, because of extensive
      osteolysis. There were two additional periprosthetic femoral fractures, which
      were treated with open reduction and internal fixation with retention of the
      components. The majority of patients had other functionally limiting conditions,
      such as spinal deformities, in addition to the degenerative arthritis.
      CONCLUSIONS: There was a high prevalence of complications, periprosthetic
      fractures, and mechanical failure in these patients with osteochondrodysplasia
      who underwent total hip arthroplasty. Young age, severe deformity, and multiple
      joint involvement may in part explain these findings. Nonetheless, total hip
      arthroplasty proved to be reliable for alleviating pain and improving function in
      patients with advanced symptomatic arthritis of the hip secondary to
      osteochondrodysplasia.

PMID- 14960675
TI  - Factors affecting the severity of backside wear of modular tibial inserts.
AB  - BACKGROUND: The use of modular tibial components in total knee arthroplasty
      introduces a possible source of polyethylene wear at the nonarticulating
      (backside) surface. However, it is not known whether this phenomenon is an
      incidental finding observed in unique specimens or is a feature common to all
      modular components. The purpose of this study was to determine the type and
      severity of backside wear in retrieved tibial inserts of several common total
      knee designs. METHODS: One hundred and twenty-four polyethylene tibial inserts of
      twelve different designs were retrieved at revision total knee replacements after
      implantation periods ranging from zero to 180 months. Each insert was visually
      inspected with use of a stereomicroscope for seven different modes of surface
      damage in four quadrants defining the backside surface. RESULTS: Pitting,
      burnishing, and measurable polyethylene protrusions were observed on the backside
      of polyethylene inserts of implant designs with a variety of different capture
      mechanisms. Across all implant designs, pitting was observed in 90% of the
      retrieved specimens; burnishing, in 77%; and protrusion, in 61%. Overall,
      implants of the IB-II (Insall-Burstein-II) design (Zimmer) exhibited the most
      severe burnishing, whereas those of the Duracon design (Howmedica) had the most
      severe pitting. Severe protrusions were noted with inserts of one design (AMK
      [Anatomic Modular Knee]; DePuy). A longer time in situ was associated with larger
      polyethylene protrusions, but the severity of pitting and burnishing did not
      increase with increasing duration of implantation. CONCLUSIONS: Moderate-to
      severe wear of the nonarticulating surface of the tibial insert was frequently
      observed in all designs of knee prostheses, independent of the capture mechanism.
      These results indicate that new designs of modular tibial components are needed
      to prevent the generation of polyethylene wear debris through backside wear of
      total knee replacements.

PMID- 14960676
TI  - Developmental hip dysplasia treated with total hip arthroplasty with a straight
      stem and a threaded cup.
AB  - BACKGROUND: Operative strategies to overcome the anatomical anomalies in patients
      with osteoarthritis secondary to developmental dysplasia of the hip remain
      controversial. The objective of this study was to determine the outcomes of total
      hip replacement with a grit-blasted cementless threaded cup and a cementless
      straight stem in patients with developmental dysplasia. METHODS: Ninety-three
      patients with developmental hip dysplasia who had been treated with a total of
      121 cementless total hip arthroplasties were clinically assessed at a mean of 9.3
      years. The acetabular reconstruction was done with a cementless threaded cup,
      which was medialized to ensure that at least one thread was anchored in the bone
      in order to achieve good primary stability. All radiographs were analyzed
      retrospectively. RESULTS: Kaplan-Meier survivorship analysis, with radiographic
      evidence of aseptic loosening as the end point, predicted a survival rate of
      97.5% for the acetabular component and 100% for the femoral stem at 9.3 years.
      The average Harris hip score for the unrevised hips improved from 34.0 points
      preoperatively to 84.1 points at the latest follow-up evaluation. The average
      total volume of polyethylene wear at the time of final follow-up was 73.6 mm(3).
      CONCLUSIONS: These wear and loosening rates demonstrate that very good results
      were achieved in this relatively young patient population when the hip joint
      center had been properly restored, even when a small cup with a thin polyethylene
      liner had been used.

PMID- 14960677
TI  - Digital resistance and tendon strength during the first week after flexor
      digitorum profundus tendon repair in a canine model in vivo.
AB  - BACKGROUND: After flexor tendon repair, the strength of the repair and the
      resistance to digital motion are important considerations in deciding when to
      initiate postoperative rehabilitation. Our objective was to assess these factors
      in a short-term in vivo canine model of flexor tendon repair. METHODS: Forty
      eight dogs were randomly allocated to four groups based on the duration of
      postoperative follow-up (one, three, five, or seven days). In each group, two
      flexor digitorum profundus tendons of one forepaw were exposed. One tendon (the
      repair tendon) was sharply transected and repaired with a modified Kessler
      suture, and the other one (the sham tendon) was simply exposed without
      laceration. The involved paw was immobilized until the animal was killed on the
      designated day. Three tendons from each dog, including the repair tendon, the
      sham tendon, and a control tendon from a corresponding normal digit on the
      contralateral side, were tested. RESULTS: The mean peak total digital resistance
      force in the repair group was lowest at five days (p < 0.01 compared with seven
      days; p > 0.05 compared with one and three days). The mean peak force needed to
      overcome the internal gliding resistance between the repaired tendon and sheath
      was significantly higher than that in both the sham and control groups at all
      time-points (p < 0.001); however, this value was also smallest at five days.
      There was no significant difference in suture strength at any time-point (p >
      0.05). CONCLUSIONS: When we evaluated tendon-gliding and suture strength after
      flexor tendon repair, the least favorable ratio of repair strength to force
      needed to overcome the resistance to digital motion was noted on Day 7, whereas
      the best combination of tendon strength and low peak resistance force was noted
      on Day 5.

PMID- 14960678
TI  - Proprioception, kinesthesia, and balance after total knee arthroplasty with
      cruciate-retaining and posterior stabilized prostheses.
AB  - BACKGROUND: The effect of total knee arthroplasty on proprioception, kinesthesia,
      and postural control remains controversial. It is argued that retaining the
      posterior cruciate ligament may help to preserve these sensorimotor functions and
      improve the longevity of the prosthesis and the functional outcome. We performed
      a prospective, randomized study to assess proprioception, kinesthesia, and
      balance following total knee arthroplasty with cruciate-retaining and posterior
      stabilized prostheses. METHODS: Twenty patients scheduled to undergo total knee
      arthroplasty were randomly assigned to receive either a cruciate-retaining or a
      posterior stabilized prosthesis. Joint-position sense, the threshold to detect
      joint motion, and the subject's ability to balance on an unstable platform were
      assessed prior to and at least six months after the operation. Paired two-tailed
      t tests (with a level of significance of p < 0.05) were used to assess the effect
      of the arthroplasty on the preoperative measures for all subjects. Analysis of
      covariance was performed to identify the effects of prosthetic design. RESULTS:
      Following total knee arthroplasty, patients detected motion significantly faster
      and reproduced joint position with less error. The balance index also improved
      significantly from the preoperative to the postoperative evaluation. The group
      treated with the posterior stabilized prosthesis more accurately reproduced joint
      position when the knee was extended from a flexed position. CONCLUSIONS: Total
      knee arthroplasty results in mild improvements in proprioception, kinesthesia,
      and balance. These changes may result from the retensioned capsuloligamentous
      structures and reduced pain and inflammation. Retention of the posterior cruciate
      ligament does not appear to significantly improve proprioception and balance
      compared with those functions in patients with a posterior stabilized total knee
      design.

PMID- 14960679
TI  - Total knee arthroplasty in patients with liver cirrhosis.
AB  - BACKGROUND: Patients with liver cirrhosis have an increased risk of surgical
      morbidity and mortality. We are aware of no study that has investigated the risks
      and outcomes of elective orthopaedic procedures in these patients. The purposes
      of the present study were to review the results of total knee arthroplasty in
      patients with cirrhosis and to identify risk factors leading to poor results.
      METHODS: Fifty-one patients with cirrhosis who had undergone sixty total knee
      arthroplasties for osteoarthritis were studied. The medical records and
      laboratory data were collected retrospectively. All data were compared with those
      for matched patients without cirrhosis. Forty-two patients (fifty-one knees) with
      complete follow-up were evaluated with regard to complications, mortality, and
      factors leading to poor results. RESULTS: Total knee arthroplasty was associated
      with significantly more blood loss, a longer hospital stay, more complications,
      and a higher mortality rate in patients with cirrhosis as compared with control
      patients (p </= 0.006 for all). Twenty-six complications occurred in twenty
      patients (twenty-two knees). Logistic regression analysis showed that a history
      of hepatic decompensation or variceal bleeding was an independent predictor of
      complications. Infection was the most common complication (prevalence, 21%). Age,
      platelet count, and hepatitis-B-related cirrhosis were independent predictors of
      infection. There were no perioperative deaths. Fifteen patients died at a mean of
      forty-three months after total knee arthroplasty; two deaths were related to the
      procedure. The presence of a hepatoma was found to be a significant predictor of
      mortality (p < 0.001). CONCLUSIONS: The rate of complications after total knee
      arthroplasty was significantly higher in patients with cirrhosis than in control
      patients (p < 0.001). We believe that total knee arthroplasty should not be
      performed in patients with a history of hepatic decompensation or variceal
      bleeding. The risk of infection was high in older patients, patients with a low
      platelet count, and patients in whom the cirrhosis was related to the hepatitis-B
      virus. Aggressive prophylaxis against infection should be performed. Patients
      with Child class-A cirrhosis without these risk factors may do well following a
      total knee arthroplasty. The benefit of total knee arthroplasty should be
      cautiously weighed against its potential risks in patients with cirrhosis.

PMID- 14960680
TI  - Factors influencing the longer-term survival of uncemented acetabular components
      used in total hip revisions.
AB  - BACKGROUND: There are few longer-term follow-up reports of the results and
      complications of the use of cementless acetabular components in revision hip
      arthroplasty. In this study, we analyzed the clinical and radiographic results to
      determine the factors that affect longer-term survival of titanium-fiber-metal
      coated acetabular components. METHODS: During a fourteen-year period, one surgeon
      performed 211 consecutive unselected cementless acetabular revisions in 194
      patients with a mean age of sixty-two years. The same technique was used for all
      revisions: the component was impacted and was fixed with multiple screws, and
      bone deficiencies were augmented with supplemental bone graft. Both the
      acetabular and the femoral components were revised in 142 hips, whereas an
      isolated acetabular revision was performed in sixty-nine hips. All 211 revisions
      were included in a survivorship analysis to twelve years. Prospectively
      determined clinical results in 135 hips and radiographic results in 131 hips were
      available at a minimum of five years postoperatively. RESULTS: Seven acetabular
      components were removed: three, because of infection; one, because of recurrent
      dislocation; and three, because of mechanical loosening. There was asymptomatic
      radiographic loosening of one additional acetabular component, for a total rate
      of aseptic loosening of 2%. The twelve-year prosthetic survival rate was 95% (95%
      confidence interval, 91% to 99%), with failure defined as component removal for
      any reason. There was no significant difference in the rate of survival of the
      cup or femoral component between the sixty-nine hips treated with isolated
      acetabular revision and the 142 hips in which both components were revised. There
      was a significant difference in the rate of dislocation between the hips treated
      with isolated acetabular revision (dislocation in fourteen hips, 20%) and those
      in which both components had been revised (dislocation in eleven hips, 8%; p =
      0.03), but there was no difference in component survival if a dislocation
      occurred. There was a significant association between a patient weight of >82 kg
      and acetabular failure (p = 0.04). CONCLUSIONS: This titanium-fiber-metal-coated
      hemispheric component fixed with multiple screws had a twelve-year survival rate
      of 95% when used in an unselected, consecutive series of acetabular revisions.
      The rate of dislocation was significantly higher in the patients treated with
      isolated acetabular revision, and routine postoperative bracing is now
      recommended for that group.

PMID- 14960681
TI  - Three-dimensional muscle-tendon geometry after rectus femoris tendon transfer.
AB  - BACKGROUND: Rectus femoris tendon transfer is performed in patients with cerebral
      palsy to improve knee flexion during walking. This procedure involves detachment
      of the muscle from its insertion into the quadriceps tendon and reattachment to
      one of the knee flexor muscles. The purpose of the present study was to evaluate
      the muscle-tendon geometry and to assess the formation of scar tissue between the
      rectus femoris and adjacent structures. METHODS: Magnetic resonance images of the
      lower extremities were acquired from five subjects after bilateral rectus femoris
      tendon transfer. A three-dimensional computer model of the musculoskeletal
      geometry of each of the ten limbs was created from these images. RESULTS: The
      three-dimensional paths of the rectus femoris muscles after transfer demonstrated
      that the muscle does not follow a straight course from its origin to its new
      insertion. The typical muscle-tendon path included an angular deviation; this
      deviation was sharp (>35 degrees ) in seven extremities. In addition, scar tissue
      between the transferred rectus femoris and the underlying muscles was visible on
      the magnetic resonance images. CONCLUSIONS: The angular deviations in the rectus
      femoris muscle-tendon path and the presence of scar tissue between the rectus
      femoris and the underlying muscles suggest that the beneficial effects of rectus
      femoris tendon transfer are derived from reducing the effects of the rectus
      femoris muscle as a knee extensor rather than from converting the muscle to a
      knee flexor. These findings clarify our understanding of the mechanism by which
      rectus femoris tendon transfer improves knee flexion.

PMID- 14960682
TI  - The effect of comorbidity on self-assessed function in patients with a chronic
      rotator cuff tear.
AB  - BACKGROUND: The results of preoperative assessment of factors that might affect
      the outcome of orthopaedic surgery have rarely been studied. In this study, we
      evaluated the relationship between the number of medical comorbidities and the
      preoperative performance on outcome assessment tools in patients with a chronic
      rotator cuff tear. METHODS: One-hundred and ninety-nine patients (206 shoulders)
      with a chronic rotator cuff tear who were treated with surgery were evaluated
      preoperatively with a detailed history (including medical comorbidities),
      physical examination, and the following outcome instruments: (1) the Disabilities
      of the Arm, Shoulder and Hand (DASH) questionnaire, (2) the Simple Shoulder Test,
      (3) visual analog scales (pain, function, and quality of life), and (4) the Short
      Form-36 (SF-36). RESULTS: The patients had a mean of 2.07 comorbidities (range,
      zero to seven comorbidities). With use of univariate regression analysis, a
      greater number of comorbidities was associated with worse function (DASH [p =
      0.0064], Simple Shoulder Test [p = 0.0001 for the best-case scenario and p =
      0.0009 for the worst-case scenario], and visual analog scale for function [p =
      0.0003] and increased pain [p = 0.05]) and with worse general health status
      (physical function [p < 0.0001], role-physical [p = 0.0286], general health [p <
      0.0001], vitality [p = 0.0014], social function [p = 0.0004], role-emotional [p =
      0.0003], and visual analog scale for quality of life [p = 0.0102]). These results
      were confirmed with significant associations (p < 0.05) between the number of
      comorbidities and the scores on the Simple Shoulder Test; DASH questionnaire;
      visual analog scales for function, pain, and quality of life; and seven of the
      eight items (all but mental health) on the SF-36 in a multivariate regression
      analysis, which included age, gender, Workers' Compensation status, number of
      previous operations, smoking history, size of the tear, duration of symptoms, and
      average patient expectations as possible confounding variables. CONCLUSIONS:
      Medical comorbidities have a negative impact on patient-reported preoperative
      baseline pain, function, and general health status associated with chronic
      rotator cuff tears. We postulate that this effect may ultimately influence the
      evaluation of the results of surgical treatment of rotator cuff tears and should
      be considered when treating patients and analyzing outcomes.

PMID- 14960683
TI  - Posttraumatic one-bone forearm reconstruction. A report of seven cases.

PMID- 14960684
TI  - Airway obstruction caused by cerebrospinal fluid leakage after anterior cervical
      spine surgery. A report of two cases.

PMID- 14960685
TI  - Avulsion fracture of the medial head of the gastrocnemius muscle. A case report.

PMID- 14960686
TI  - Damage of an alumina-on-alumina bearing surface from a difficult reduction of a
      total hip arthroplasty. A report of three cases.

PMID- 14960687
TI  - Thoracic disc herniation presenting with chronic nausea and abdominal pain. A
      case report.

PMID- 14960688
TI  - Low-back pain in athletes.
AB  - While most occurrences of low-back pain in athletes are self-limited sprains or
      strains, persistent, chronic, or recurrent symptoms are frequently associated
      with degenerative lumbar disc disease or spondylolytic stress lesions. The
      prevalence of radiographic evidence of disc degeneration is higher in athletes
      than it is in nonathletes; however, it remains unclear whether this correlates
      with a higher rate of back pain. Although there is little peer-reviewed clinical
      information on the subject, it is possible that chronic pain from degenerative
      disc disease that is recalcitrant after intensive and continuous nonoperative
      care can be successfully treated with interbody fusion in selected athletes. In
      general, the prevalence of spondylolysis is not higher in athletes than it is in
      nonathletes, although participation in sports involving repetitive hyperextension
      maneuvers, such as gymnastics, wrestling, and diving, appears to be associated
      with disproportionately higher rates of spondylolysis. Nonoperative treatment of
      spondylolysis results in successful pain relief in approximately 80% of athletes,
      independent of radiographic evidence of defect healing. In recalcitrant cases,
      direct surgical repair of the pars interarticularis with internal fixation and
      bone-grafting can yield high rates of pain relief in competitive athletes and
      allow a high percentage to return to play. Sacral stress fractures occur almost
      exclusively in individuals participating in high-level running sports, such as
      track or marathon. Treatment includes a brief period of limited weight-bearing
      followed by progressive mobilization, physical therapy, and return to sports in
      one to two months, when the pain has resolved.

PMID- 14960690
TI  - An AOA critical issue. Disc replacements: this time will we really cure low-back
      and neck pain?

PMID- 14960691
TI  - Conflict of interest in orthopaedic research.
AB  - BACKGROUND: The expanding role of industrial support in biomedical research has
      resulted in both substantial interest and controversy in recent years. Our
      hypothesis was that, from 1985 to 2002, the role of industrial support in
      orthopaedic research increased, as documented by the research presented at the
      annual meetings of the American Academy of Orthopaedic Surgeons. METHODS: We
      analyzed the frequency and types of self-reported conflicts of interest for all
      presentations at the annual meetings of the American Academy of Orthopaedic
      Surgeons in 1985, 1988, 1992, 1997, 1999, and 2002. Conflicts of interest were
      recorded directly from the final program for each meeting analyzed. The analysis
      focused on the scientific presentations, Instructional Course Lectures, symposia,
      poster exhibits, and scientific exhibits. Information about specific types of
      support received by authors was first required in 1988. RESULTS: The incidence of
      conflicts of interest increased from 3% in 1985 to 39% in 2002 for scientific
      papers (p < 0.001); from 10% to 74%, respectively, for symposia (p < 0.001); from
      22% to 60% for Instructional Course Lectures (p < 0.001); from 10% to 60% for
      scientific exhibits (p < 0.001); and from 9% in 1992 to 14% in 2002 for posters
      (p < 0.001). For presentations of all types, the incidence increased from 10% to
      32% (p < 0.001). The types of conflict of interest also changed significantly
      from 1999 to 2002. In 1999, 73% of conflicts were documented as support directed
      to institutions and 27%, as support to individuals; in 2002, 57% were reported as
      support directed to institutions and 43%, as support to individuals (p < 0.01).
      CONCLUSIONS: The role of industrial support of orthopaedic research increased
      significantly between 1985 and 2002, as evidenced by the increase in the self
      reported conflicts of interest for all types of presentations at the annual
      meetings of the American Academy of Orthopaedic Surgeons. In addition, the
      support directed to individuals, in contrast to that directed to institutions,
      increased significantly.

PMID- 14960692
TI  - Position of the aorta relative to the spine in idiopathic scoliosis.

PMID- 14960693
TI  - Ethics in practice: transferring patients after complications of treatment.

PMID- 14960694
TI  - Fixation of type-C tibial plafond fractures.

PMID- 14960695
TI  - Primary compared with salvage arthroplasty for displaced intracapsular hip
      fractures.

PMID- 14960696
TI  - Lower-extremity function for driving an automobile after operative treatment of
      ankle fracture.

PMID- 14960697
TI  - Anatomical variants in the anterosuperior aspect of the glenoid labrum.

PMID- 14960698
TI  - Accuracy of needle placement into the intra-articular space of the knee.

PMID- 14960699
TI  - Ten-year results with hydroxyapatite-coated total hip femoral components in
      patients less than fifty years old.

PMID- 14960700
TI  - Long-term outcome after tibial shaft fracture: is malunion important?

PMID- 14960701
TI  - Reduction increasing osteonecrosis risk in slipped capital femoral epiphysis.

PMID- 14960706
TI  - What's new in hand surgery.

PMID- 14960708
TI  - Determination of detection and quantification limits for SNP allele frequency
      estimation in DNA pools using real time PCR.
AB  - The quantification of single nucleotide polymorphism (SNP) allele frequencies in
      pooled DNA samples using real time PCR is a promising approach for large-scale
      diagnostics and genotyping. The limits of detection (LOD) and limits of
      quantification (LOQ) for mutant SNP alleles are of particular importance for
      determination of the working range, which, in the case of allele-specific real
      time PCR, can be limited by the variance of calibration data from serially
      diluted mutant allele samples as well as by the variance of the 100% wild-type
      allele samples (blank values). In this study, 3sigma and 10sigma criteria were
      applied for the calculation of LOD and LOQ values. Alternatively, LOQ was derived
      from a 20% threshold for the relative standard deviation (%RSD) of measurements
      by fitting a curve for the relationship between %RSD and copy numbers of the
      mutant alleles. We found that detection and quantification of mutant alleles were
      exclusively limited by the variance of calibration data since the estimated
      LOD(calibration) (696 in 30 000 000 copies, 0.0023%), LOQ(20%RSD) (1470, 0.0049%)
      and LOQ(calibration) (2319, 0.0077) values were significantly higher than the
      LOD(blank) (130, 0.0004%) and LOQ(blank) (265, 0.0009%) values derived from
      measurements of wild-type allele samples. No significant matrix effects of the
      genomic background DNA on the estimation of LOD and LOQ were found. Furthermore,
      the impact of large genome sizes and the general application of the procedure for
      the estimation of LOD and LOQ in quantitative real time PCR diagnostics are
      discussed.

PMID- 14960709
TI  - Nuclear localization signal and cell synchrony enhance gene targeting efficiency
      in primary fetal fibroblasts.
AB  - The use of primary somatic cells in nuclear transfer procedure has opened a new
      opportunity to manipulate domestic animal genomes via homologous recombination.
      To date, while a few loci have been targeted in somatic cells using similar
      enrichment strategies as those used in mouse ES cells, there have been problems
      of low efficiency, mixed targeted and non-targeted cells within a colony and
      difficulties in cloning the cell after targeting. Utilizing the hypoxanthine
      guanine phosphoribosyl transferase (HPRT) as a test locus, it was determined that
      while no targeted colonies were identified using a conventional targeting
      construct, an average of 1 per million targeted cells were identified when a
      nuclear localization signal (nls) was added to the construct. When the nls was
      combined with cell synchronization using a thymidine block, targeting efficiency
      increased 7-fold. Moreover, the number of random integrants decreased by over 54
      fold resulting in a 1:3 targeted to random integration ratio. This method should
      facilitate the application of homologous recombination to primary somatic cells.

PMID- 14960710
TI  - Genomic shotgun array: a procedure linking large-scale DNA sequencing with
      regional transcript mapping.
AB  - To facilitate transcript mapping and to investigate alterations in genomic
      structure and gene expression in a defined genomic target, we developed a novel
      microarray-based method to detect transcriptional activity of the human
      chromosome 4q22-24 region. Loss of heterozygosity of human 4q22-24 is frequently
      observed in hepatocellular carcinoma (HCC). One hundred and eighteen well
      characterized genes have been identified from this region. We took previously
      sequenced shotgun subclones as templates to amplify overlapping sequences for the
      genomic segment and constructed a chromosome-region-specific microarray. Using
      genomic DNA fragments as probes, we detected transcriptional activity from within
      this region among five different tissues. The hybridization results indicate that
      there are new transcripts that have not yet been identified by other methods. The
      existence of new transcripts encoded by genes in this region was confirmed by PCR
      cloning or cDNA library screening. The procedure reported here allows coupling of
      shotgun sequencing with transcript mapping and, potentially, detailed analysis of
      gene expression and chromosomal copy of the genomic sequence for the putative HCC
      tumor suppressor gene(s) in the 4q candidate region.

PMID- 14960711
TI  - Semiconductor nanocrystal probes for human metaphase chromosomes.
AB  - To improve signal stability and quantitation, an optically stable, novel class of
      fluorophore for hybridization analysis of human metaphase chromosomes is
      demonstrated. Detection of hybridization sites in situ was based on fluorescence
      from streptavidin-linked inorganic crystals of cadmium selenide [(CdSe)ZnS].
      Fluorescence of nanocrystal fluorophores was significantly brighter and more
      photostable than organic fluorophores Texas Red and fluorescein. Thus,
      semiconductor nanocrystal fluorophores offer a more stable and quantitative mode
      of fluorescence in situ hybridization (FISH) for research and clinical
      applications.

PMID- 14960712
TI  - Biochemical characterization of the mitochondrial tRNASer(UCN) T7511C mutation
      associated with nonsyndromic deafness.
AB  - We report here the biochemical characterization of the deafness-associated
      mitochondrial tRNA(Ser(UCN)) T7511C mutation, in conjunction with homoplasmic ND1
      T3308C and tRNA(Ala) T5655C mutations using cybrids constructed by transferring
      mitochondria from lymphoblastoid cell lines derived from an African family into
      human mtDNA-less (rho degrees ) cells. Three cybrids derived from an affected
      matrilineal relative carrying the homoplasmic T7511C mutation, exhibited
      approximately 75% decrease in the tRNA(Ser(UCN)) level, compared with three
      control cybrids. This amount of reduction in the tRNA(Ser(UCN)) level is below a
      proposed threshold to support a normal rate of mitochondrial protein synthesis in
      lymphoblastoid cell lines. This defect is likely a primary contributor to
      approximately 52% reduction in the rate of mitochondrial protein synthesis and
      marked defects in respiration and growth properties in galactose-containing
      medium. Interestingly, the T5655C mutation produces approximately 50% reduction
      in the tRNA(Ala) level in mutant cells. Strikingly, the T3308C mutation causes a
      significant decrease both in the amount of ND1 mRNA and co-transcribed
      tRNA(Leu(UUR)) in mutant cells. Thus, mitochondrial dysfunctions caused by the
      T5655C and T3308C mutations may modulate the phenotypic manifestation of the
      T7511C mutation. These observations imply that a combination of the T7511C
      mutation with two mtDNA mutations accounts for the high penetrance of deafness in
      this family.

PMID- 14960714
TI  - The genome sequence of Bacillus cereus ATCC 10987 reveals metabolic adaptations
      and a large plasmid related to Bacillus anthracis pXO1.
AB  - We sequenced the complete genome of Bacillus cereus ATCC 10987, a non-lethal
      dairy isolate in the same genetic subgroup as Bacillus anthracis. Comparison of
      the chromosomes demonstrated that B.cereus ATCC 10987 was more similar to
      B.anthracis Ames than B.cereus ATCC 14579, while containing a number of unique
      metabolic capabilities such as urease and xylose utilization and lacking the
      ability to utilize nitrate and nitrite. Additionally, genetic mechanisms for
      variation of capsule carbohydrate and flagella surface structures were
      identified. Bacillus cereus ATCC 10987 contains a single large plasmid
      (pBc10987), of approximately 208 kb, that is similar in gene content and
      organization to B.anthracis pXO1 but is lacking the pathogenicity-associated
      island containing the anthrax lethal and edema toxin complex genes. The
      chromosomal similarity of B.cereus ATCC 10987 to B.anthracis Ames, as well as the
      fact that it contains a large pXO1-like plasmid, may make it a possible model for
      studying B.anthracis plasmid biology and regulatory cross-talk.

PMID- 14960713
TI  - The diverse superfamily of lysine acetyltransferases and their roles in leukemia
      and other diseases.
AB  - Acetylation of the epsilon-amino group of lysine residues, or N(epsilon)-lysine
      acetylation, is an important post-translational modification known to occur in
      histones, transcription factors and other proteins. Since 1995, dozens of
      proteins have been discovered to possess intrinsic lysine acetyltransferase
      activity. Although most of these enzymes were first identified as histone
      acetyltransferases and then tested for activities towards other proteins,
      acetyltransferases only modifying non-histone proteins have also been identified.
      Lysine acetyltransferases form different groups, three of which are Gcn5/PCAF,
      p300/CBP and MYST proteins. While members of the former two groups mainly
      function as transcriptional co-activators, emerging evidence suggests that MYST
      proteins, such as Esa1, Sas2, MOF, TIP60, MOZ and MORF, have diverse roles in
      various nuclear processes. Aberrant lysine acetylation has been implicated in
      oncogenesis. The genes for p300, CBP, MOZ and MORF are rearranged in recurrent
      leukemia-associated chromosomal abnormalities. Consistent with their roles in
      leukemogenesis, these acetyltransferases interact with Runx1 (or AML1), one of
      the most frequent targets of chromosomal translocations in leukemia. Therefore,
      the diverse superfamily of lysine acetyltransferases executes an acetylation
      program that is important for different cellular processes and perturbation of
      such a program may cause the development of cancer and other diseases.

PMID- 14960715
TI  - Mycobacterium tuberculosis Rv2118c codes for a single-component homotetrameric
      m1A58 tRNA methyltransferase.
AB  - Modified nucleosides in tRNAs play important roles in tRNA structure,
      biosynthesis and function, and serve as crucial determinants of bacterial growth
      and virulence. In the yeast Saccharomyces cerevisiae, mutants defective in N1
      methylation of a highly conserved adenosine (A58) in the TPsiC loop of initiator
      tRNA are non-viable. The yeast m1A58 methyltransferase is a heterotetramer
      consisting of two different polypeptide chains, Gcd14p and Gcd10p. Interestingly,
      while m1A58 is not found in most eubacteria, the mycobacterial tRNAs have m1A58.
      Here, we report on the cloning, overexpression, purification and biochemical
      characterization of the Rv2118c gene-encoded protein (Rv2118p) from Mycobacterium
      tuberculosis, which is homologous to yeast Gcd14p. We show that Rv2118c codes for
      a protein of approximately 31 kDa. Activity assays, modified base analysis and
      primer extension experiments using reverse transcriptase reveal that Rv2118p is
      an S-adenosyl-l-methionine-dependent methyltransferase which carries out m1A58
      modification in tRNAs, both in vivo and in vitro. Remarkably, when expressed in
      Escherichia coli, the enzyme methylates the endogenous E.coli initiator tRNA
      essentially quantitatively. Furthermore, unlike its eukaryotic counterpart, which
      is a heterotetramer, the mycobacterial enzyme is a homotetramer. Also, the
      presence of rT modification at position 54, which was found to inhibit the
      Tetrahymena pyriformis enzyme, does not affect the activity of Rv2118p. Thus, the
      mycobacterial m1A58 tRNA methyltransferase possesses distinct biochemical
      properties. We discuss aspects of the biological relevance of Rv2118p in
      M.tuberculosis, and its potential use as a drug target to control the growth of
      mycobacteria.

PMID- 14960716
TI  - The importance of intrinsic disorder for protein phosphorylation.
AB  - Reversible protein phosphorylation provides a major regulatory mechanism in
      eukaryotic cells. Due to the high variability of amino acid residues flanking a
      relatively limited number of experimentally identified phosphorylation sites,
      reliable prediction of such sites still remains an important issue. Here we
      report the development of a new web-based tool for the prediction of protein
      phosphorylation sites, DISPHOS (DISorder-enhanced PHOSphorylation predictor,
      http://www.ist.temple. edu/DISPHOS). We observed that amino acid compositions,
      sequence complexity, hydrophobicity, charge and other sequence attributes of
      regions adjacent to phosphorylation sites are very similar to those of
      intrinsically disordered protein regions. Thus, DISPHOS uses position-specific
      amino acid frequencies and disorder information to improve the discrimination
      between phosphorylation and non-phosphorylation sites. Based on the estimates of
      phosphorylation rates in various protein categories, the outputs of DISPHOS are
      adjusted in order to reduce the total number of misclassified residues. When
      tested on an equal number of phosphorylated and non-phosphorylated residues, the
      accuracy of DISPHOS reaches 76% for serine, 81% for threonine and 83% for
      tyrosine. The significant enrichment in disorder-promoting residues surrounding
      phosphorylation sites together with the results obtained by applying DISPHOS to
      various protein functional classes and proteomes, provide strong support for the
      hypothesis that protein phosphorylation predominantly occurs within intrinsically
      disordered protein regions.

PMID- 14960717
TI  - Biased distribution of DNA uptake sequences towards genome maintenance genes.
AB  - Repeated sequence signatures are characteristic features of all genomic DNA. We
      have made a rigorous search for repeat genomic sequences in the human pathogens
      Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae and
      found that by far the most frequent 9-10mers residing within coding regions are
      the DNA uptake sequences (DUS) required for natural genetic transformation. More
      importantly, we found a significantly higher density of DUS within genes involved
      in DNA repair, recombination, restriction-modification and replication than in
      any other annotated gene group in these organisms. Pasteurella multocida also
      displayed high frequencies of a putative DUS identical to that previously
      identified in H.influenzae and with a skewed distribution towards genome
      maintenance genes, indicating that this bacterium might be transformation
      competent under certain conditions. These results imply that the high frequency
      of DUS in genome maintenance genes is conserved among phylogenetically divergent
      species and thus are of significant biological importance. Increased DUS density
      is expected to enhance DNA uptake and the over-representation of DUS in genome
      maintenance genes might reflect facilitated recovery of genome preserving
      functions. For example, transient and beneficial increase in genome instability
      can be allowed during pathogenesis simply through loss of antimutator genes,
      since these DUS-containing sequences will be preferentially recovered.
      Furthermore, uptake of such genes could provide a mechanism for facilitated
      recovery from DNA damage after genotoxic stress.

PMID- 14960718
TI  - Structure-function correlations derived from faster variants of a RNA ligase
      deoxyribozyme.
AB  - We previously reported the in vitro selection of several Mg2+-dependent
      deoxyribozymes (DNA enzymes) that synthesize a 2'-5' RNA linkage from a 2',3'
      cyclic phosphate and a 5'-hydroxyl. Here we subjected the 9A2 deoxyribozyme to re
      selection for improved ligation rate. We found two new DNA enzymes (7Z81 and
      7Z48) that contain the catalytic core of 7Q10, a previously reported small
      deoxyribozyme that is unrelated in sequence to 9A2. A third new DNA enzyme
      (7Z101) is unrelated to either 7Q10 or 9A2. The new 7Z81 and 7Z48 DNA enzymes
      have ligation rates over an order of magnitude higher than that of 7Q10 itself
      and they have additional sequence elements that correlate with these faster
      rates. Our findings provide insight into structure-function relationships of
      catalytic nucleic acids.

PMID- 14960719
TI  - A thymine tetrad in d(TGGGGT) quadruplexes stabilized with Tl+/Na+ ions.
AB  - We report two new structures of the quadruplex d(TGGGGT)4 obtained by single
      crystal X-ray diffraction. In one of them a thymine tetrad is found. Thus the
      yeast telomere sequences d(TG1-3) might be able to form continuous quadruplex
      structures, involving both guanine and thymine tetrads. Our study also shows
      substantial differences in the arrangement of thymines when compared with
      previous studies. We find five different types of organization: (i) groove
      binding with hydrogen bonds to guanines from a neighbour quadruplex; (ii)
      partially ordered groove binding, without any hydrogen bond; (iii) stacked
      thymine triads, formed at the 3'ends of the quadruplexes; (iv) a thymine tetrad
      between two guanine tetrads. Thymines are stabilized in pairs by single hydrogen
      bonds. A central sodium ion interacts with two thymines and contributes to the
      tetrad structure. (v) Completely disordered thymines which do not show any clear
      location in the crystal. The tetrads are stabilized by either Na+ or Tl+ ions. We
      show that by using MAD methods, Tl+ can be unambiguously located and
      distinguished from Na+. We can thus determine the preference for either ion in
      each ionic site of the structure under the conditions used by us.

PMID- 14960720
TI  - Assembly of the replication initiation complex on SV40 origin DNA.
AB  - The assembly of the complex that forms over the simian virus 40 origin to
      initiate DNA replication is not well understood. This complex is composed of the
      virus-coded T antigen and three cellular proteins, replication protein A (RPA),
      DNA polymerase alpha/primase (pol/prim) and topoisomerase I (topo I) in
      association with the origin. The order in which these various proteins bind to
      the DNA was investigated by performing binding assays using biotinylated origin
      DNA. We demonstrate that in the presence of all four proteins, pol/prim was
      essential to stabilize the initiation complex from the disruptive effects of topo
      I. At the optimal concentration of pol/prim, topo I and RPA bound efficiently to
      the complex, although pol/prim itself was not detected in significant amounts. At
      higher concentrations less topo I was recruited, suggesting that DNA polymerase
      is an important modulator of the binding of topo I. Topo I, in turn, appeared to
      be involved in recruiting RPA. RPA, in contrast, seemed to have little or no
      effect on the recruitment of the other proteins to the origin. These and other
      data suggested that pol/prim is the first cellular protein to interact with the
      double-hexameric T antigen bound to the origin. This is likely followed by topo I
      and then RPA, or perhaps by a complex of topo I and RPA. Stoichiometric analysis
      of the topo I and T antigen present in the complex suggested that two molecules
      of topo I are recruited per double hexamer. Finally, we demonstrate that DNA has
      a role in recruiting topo I to the origin.

PMID- 14960721
TI  - The inhibition of the human cholesterol 7alpha-hydroxylase gene (CYP7A1) promoter
      by fibrates in cultured cells is mediated via the liver x receptor alpha and
      peroxisome proliferator-activated receptor alpha heterodimer.
AB  - In previous work, we showed that the binding of the liver x receptor
      alpha:peroxisome proliferator-activated receptor alpha (LXRalpha:PPARalpha)
      heterodimer to the murine Cyp7a1 gene promoter antagonizes the stimulatory effect
      of their respective ligands. In this study, we determined if LXRalpha:PPARalpha
      can also regulate human CYP7A1 gene promoter activity. Co-expression of LXRalpha
      and PPARalpha in McArdle RH7777 hepatoma cells decreased the activity of the
      human CYP7A1 gene promoter in response to fibrates and 25-hydroxycholesterol. In
      vitro, the human CYP7A1 Site I bound LXRalpha:PPARalpha, although with
      substantially less affinity compared with the murine Cyp7a1 Site I. The binding
      of LXRalpha:PPARalpha to human CYP7A1 Site I was increased in the presence of
      either LXRalpha or PPARalpha ligands. In HepG2 hepatoblastoma cells, fibrates and
      25-hydroxycholesterol inhibited the expression of the endogenous CYP7A1 gene as
      well as the human CYP7A1 gene promoter when co-transfected with plasmids encoding
      LXRalpha and PPARalpha. However, a derivative of the human CYP7A1 gene promoter
      that contains a mutant form of Site I that does not bind LXRalpha:PPARalpha was
      not inhibited by WY 14,643 or 25-hydroxycholesterol in both McArdle RH7777 and
      HepG2 cells. The ligand-dependent recruitment of LXRalpha:PPARalpha heterodimer
      onto the human CYP7A1 Site I can explain the inhibition of the human CYP7A1 gene
      promoter in response to fibrates and 25-hydroxycholesterol.

PMID- 14960722
TI  - Translesion synthesis of acetylaminofluorene-dG adducts by DNA polymerase zeta is
      stimulated by yeast Rev1 protein.
AB  - Translesion synthesis is an important mechanism in response to unrepaired DNA
      lesions during replication. The DNA polymerase zeta (Polzeta) mutagenesis pathway
      is a major error-prone translesion synthesis mechanism requiring Polzeta and
      Rev1. In addition to its dCMP transferase, a non-catalytic function of Rev1 is
      suspected in cellular response to certain types of DNA lesions. However, it is
      not well understood about the non-catalytic function of Rev1 in translesion
      synthesis. We have analyzed the role of Rev1 in translesion synthesis of an
      acetylaminofluorene (AAF)-dG DNA adduct. Purified yeast Rev1 was essentially
      unresponsive to a template AAF-dG DNA adduct, in contrast to its efficient C
      insertion opposite a template 1,N6-ethenoadenine adduct. Purified yeast Polzeta
      was very inefficient in the bypass of the AAF-dG adduct. Combining Rev1 and
      Polzeta, however, led to a synergistic effect on translesion synthesis. Rev1
      protein enhanced Polzeta-catalyzed nucleotide insertion opposite the AAF-dG
      adduct and strongly stimulated Polzeta-catalyzed extension from opposite the
      lesion. Rev1 also stimulated the deficient synthesis by Polzeta at the very end
      of undamaged DNA templates. Deleting the C-terminal 205 aa of Rev1 did not affect
      its dCMP transferase activity, but abolished its stimulatory activity on Polzeta
      catalyzed extension from opposite the AAF-dG adduct. These results suggest that
      translesion synthesis of AAF-dG adducts by Polzeta is stimulated by Rev1 protein
      in yeast. Consistent with the in vitro results, both Polzeta and Rev1 were found
      to be equally important for error-prone translesion synthesis across from AAF-dG
      DNA adducts in yeast cells.

PMID- 14960723
TI  - Analysis and recognition of 5' UTR intron splice sites in human pre-mRNA.
AB  - Prediction of splice sites in non-coding regions of genes is one of the most
      challenging aspects of gene structure recognition. We perform a rigorous analysis
      of such splice sites embedded in human 5' untranslated regions (UTRs), and
      investigate correlations between this class of splice sites and other features
      found in the adjacent exons and introns. By restricting the training of neural
      network algorithms to 'pure' UTRs (not extending partially into protein coding
      regions), we for the first time investigate the predictive power of the splicing
      signal proper, in contrast to conventional splice site prediction, which
      typically relies on the change in sequence at the transition from protein coding
      to non-coding. By doing so, the algorithms were able to pick up subtler splicing
      signals that were otherwise masked by 'coding' noise, thus enhancing
      significantly the prediction of 5' UTR splice sites. For example, the non-coding
      splice site predicting networks pick up compositional and positional bias in the
      3' ends of non-coding exons and 5' non-coding intron ends, where cytosine and
      guanine are over-represented. This compositional bias at the true UTR donor sites
      is also visible in the synaptic weights of the neural networks trained to
      identify UTR donor sites. Conventional splice site prediction methods perform
      poorly in UTRs because the reading frame pattern is absent. The NetUTR method
      presented here performs 2-3-fold better compared with NetGene2 and GenScan in 5'
      UTRs. We also tested the 5' UTR trained method on protein coding regions, and
      discovered, surprisingly, that it works quite well (although it cannot compete
      with NetGene2). This indicates that the local splicing pattern in UTRs and coding
      regions is largely the same. The NetUTR method is made publicly available at
      www.cbs.dtu.dk/services/NetUTR.

PMID- 14960727
TI  - Expression of an active tobacco mitogen-activated protein kinase kinase kinase
      enhances freezing tolerance in transgenic maize.
AB  - Cold acclimation is the major process that prepares plants for freezing
      tolerance. In addition to extensive transcription regulation by cold-inducible
      master transcription factors, oxidative stress signaling has been postulated to
      play a role in freezing tolerance. Activation of oxidative signaling through the
      expression of an active mitogen-activated protein kinase kinase kinase provided
      benefits in transgenic tobacco at freezing temperature bypassing cold
      acclimation. Because involvement of the mitogen-activated protein kinase cascade
      in oxidative stress signaling is evolutionarily conserved in eukaryotes from
      yeast to mammals, we tested the effect of expressing a heterologous tobacco
      mitogen-activated protein kinase kinase kinase (Nicotiana PK1), which can mimic
      H(2)O(2) signaling, in a major cereal crop. We demonstrate that low-level but
      constitutive expression of the Nicotiana PK1 gene enhances freezing tolerance in
      transgenic maize plants that are normally frost sensitive. Our results suggest
      that a new molecular approach can be designed to genetically enhance freezing
      tolerance in important crops.

PMID- 14960731
TI  - An efficient, palladium-catalyzed, enantioselective synthesis of (2R)-3-butene
      1,2-diol and its use in highly selective Heck reactions.
AB  - A robust and scalable procedure for the palladium-catalyzed dynamic kinetic
      asymmetric transformation of 3,4-epoxy-1-butene into (2R)-3-butene-1,2-diol with
      water as the cosolvent is reported. Examination of the effects of solvent and
      temperature led to the identification of conditions that permitted use of 0.025
      mol % catalyst, providing (2R)-3-butene-1,2-diol in 84% isolated yield and 85%
      enantiomeric excess. Subsequent Heck reactions with a diverse range of coupling
      partners are described and the influence of their electronic nature on
      maintaining the enantiopurity of the diol is discussed.

PMID- 14960734
TI  - The genetics of geometry.
AB  - Although much progress has been made in understanding how gene expression
      patterns are established during development, much less is known about how these
      patterns are related to the growth of biological shapes. Here we describe
      conceptual and experimental approaches to bridging this gap, with particular
      reference to plant development where lack of cell movement simplifies matters.
      Growth and shape change in plants can be fully described with four types of
      regional parameter: growth rate, anisotropy, direction, and rotation. A key
      requirement is to understand how these parameters both influence and respond to
      the action of genes. This can be addressed by using mechanistic models that
      capture interactions among three components: regional identities, regionalizing
      morphogens, and polarizing morphogens. By incorporating these interactions within
      a growing framework, it is possible to generate shape changes and associated gene
      expression patterns according to particular hypotheses. The results can be
      compared with experimental observations of growth of normal and mutant forms,
      allowing further hypotheses and experiments to be formulated. We illustrate these
      principles with a study of snapdragon petal growth.

PMID- 14960738
TI  - Causation of type 2 diabetes -- the Gordian knot unravels.

PMID- 14960739
TI  - Spinal-fusion surgery -- advances and concerns.

PMID- 14960740
TI  - Getting polio eradication back on track in Nigeria.

PMID- 14960741
TI  - Use of B-type natriuretic peptide in the evaluation and management of acute
      dyspnea.
AB  - BACKGROUND: B-type natriuretic peptide levels are higher in patients with
      congestive heart failure than in patients with dyspnea from other causes.
      METHODS: We conducted a prospective, randomized, controlled study of 452 patients
      who presented to the emergency department with acute dyspnea: 225 patients were
      randomly assigned to a diagnostic strategy involving the measurement of B-type
      natriuretic peptide levels with the use of a rapid bedside assay, and 227 were
      assessed in a standard manner. The time to discharge and the total cost of
      treatment were the primary end points. RESULTS: Base-line demographic and
      clinical characteristics were well matched between the two groups. The use of B
      type natriuretic peptide levels reduced the need for hospitalization and
      intensive care; 75 percent of patients in the B-type natriuretic peptide group
      were hospitalized, as compared with 85 percent of patients in the control group
      (P=0.008), and 15 percent of those in the B-type natriuretic peptide group
      required intensive care, as compared with 24 percent of those in the control
      group (P=0.01). The median time to discharge was 8.0 days in the B-type
      natriuretic peptide group and 11.0 days in the control group (P=0.001). The mean
      total cost of treatment was 5,410 dollars (95 percent confidence interval, 4,516
      dollars to 6,304 dollars) in the B-type natriuretic peptide group, as compared
      with 7,264 dollars (95 percent confidence interval, 6,301 dollars to 8,227
      dollars) in the control group (P=0.006). The respective 30-day mortality rates
      were 10 percent and 12 percent (P=0.45). CONCLUSIONS: Used in conjunction with
      other clinical information, rapid measurement of B-type natriuretic peptide in
      the emergency department improved the evaluation and treatment of patients with
      acute dyspnea and thereby reduced the time to discharge and the total cost of
      treatment.

PMID- 14960742
TI  - Plasma natriuretic peptide levels and the risk of cardiovascular events and
      death.
AB  - BACKGROUND: The natriuretic peptides are counterregulatory hormones involved in
      volume homeostasis and cardiovascular remodeling. The prognostic significance of
      plasma natriuretic peptide levels in apparently asymptomatic persons has not been
      established. METHODS: We prospectively studied 3346 persons without heart
      failure. Using proportional-hazards regression, we examined the relations of
      plasma B-type natriuretic peptide and N-terminal pro-atrial natriuretic peptide
      to the risk of death from any cause, a first major cardiovascular event, heart
      failure, atrial fibrillation, stroke or transient ischemic attack, and coronary
      heart disease. RESULTS: During a mean follow-up of 5.2 years, 119 participants
      died and 79 had a first cardiovascular event. After adjustment for cardiovascular
      risk factors, each increment of 1 SD in log B-type natriuretic peptide levels was
      associated with a 27 percent increase in the risk of death (P=0.009), a 28
      percent increase in the risk of a first cardiovascular event (P=0.03), a 77
      percent increase in the risk of heart failure (P<0.001), a 66 percent increase in
      the risk of atrial fibrillation (P<0.001), and a 53 percent increase in the risk
      of stroke or transient ischemic attack (P=0.002). Peptide levels were not
      significantly associated with the risk of coronary heart disease events. B-type
      natriuretic peptide values above the 80th percentile (20.0 pg per milliliter for
      men and 23.3 pg per milliliter for women) were associated with multivariable
      adjusted hazard ratios of 1.62 for death (P=0.02), 1.76 for a first major
      cardiovascular event (P=0.03), 1.91 for atrial fibrillation (P=0.02), 1.99 for
      stroke or transient ischemic attack (P=0.02), and 3.07 for heart failure
      (P=0.002). Similar results were obtained for N-terminal pro-atrial natriuretic
      peptide. CONCLUSIONS: In this community-based sample, plasma natriuretic peptide
      levels predicted the risk of death and cardiovascular events after adjustment for
      traditional risk factors. Excess risk was apparent at natriuretic peptide levels
      well below current thresholds used to diagnose heart failure.

PMID- 14960743
TI  - Impaired mitochondrial activity in the insulin-resistant offspring of patients
      with type 2 diabetes.
AB  - BACKGROUND: Insulin resistance appears to be the best predictor of the
      development of diabetes in the children of patients with type 2 diabetes, but the
      mechanism responsible is unknown. METHODS: We performed hyperinsulinemic
      euglycemic clamp studies in combination with infusions of [6,6-(2)H(2)]glucose in
      healthy, young, lean, insulin-resistant offspring of patients with type 2
      diabetes and insulin-sensitive control subjects matched for age, height, weight,
      and physical activity to assess the sensitivity of liver and muscle to insulin.
      Proton ((1)H) magnetic resonance spectroscopy studies were performed to measure
      intramyocellular lipid and intrahepatic triglyceride content. Rates of whole-body
      and subcutaneous fat lipolysis were assessed by measuring the rates of
      [(2)H(5)]glycerol turnover in combination with microdialysis measurements of
      glycerol release from subcutaneous fat. We performed (31)P magnetic resonance
      spectroscopy studies to assess the rates of mitochondrial oxidative
      phosphorylation activity in muscle. RESULTS: The insulin-stimulated rate of
      glucose uptake by muscle was approximately 60 percent lower in the insulin
      resistant subjects than in the insulin-sensitive control subjects (P<0.001) and
      was associated with an increase of approximately 80 percent in the
      intramyocellular lipid content (P=0.005). This increase in intramyocellular lipid
      content was most likely attributable to mitochondrial dysfunction, as reflected
      by a reduction of approximately 30 percent in mitochondrial phosphorylation
      (P=0.01 for the comparison with controls), since there were no significant
      differences in systemic or localized rates of lipolysis or plasma concentrations
      of tumor necrosis factor alpha, interleukin-6, resistin, or adiponectin.
      CONCLUSIONS: These data support the hypothesis that insulin resistance in the
      skeletal muscle of insulin-resistant offspring of patients with type 2 diabetes
      is associated with dysregulation of intramyocellular fatty acid metabolism,
      possibly because of an inherited defect in mitochondrial oxidative
      phosphorylation.

PMID- 14960744
TI  - Clinical practice. Acute renal colic from ureteral calculus.

PMID- 14960745
TI  - Islet transplantation as a treatment for diabetes - a work in progress.

PMID- 14960746
TI  - Images in clinical medicine. A message from the gut.

PMID- 14960747
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 5-2004 - a 57-year-old man with slurred speech and left
      hemiparesis.

PMID- 14960748
TI  - B-type natriuretic peptide - a biomarker for all seasons?

PMID- 14960750
TI  - Spinal-fusion surgery - the case for restraint.

PMID- 14960751
TI  - Letrozole in breast cancer.

PMID- 14960752
TI  - Trends in rates of myocardial infarction among patients with HIV.

PMID- 14960753
TI  - Extraneural pathologic prion protein.

PMID- 14960754
TI  - End-of-life care for patients with dementia.

PMID- 14960755
TI  - Implantable cardioverter-defibrillators and complications.

PMID- 14960756
TI  - Leukotriene-receptor inhibition for the treatment of systemic mastocytosis.

PMID- 14960757
TI  - Images in clinical medicine. Use of multinucleated giant cells to diagnose a
      viral eruption.

PMID- 14960758
TI  - A turn from the worm.

PMID- 14960759
TI  - Cell death, start to finish.

PMID- 14960760
TI  - Resistance training.

PMID- 14960761
TI  - Search for methuselah genes heats up.
AB  - In a recent article, Morley and Morimoto confirm previous studies suggesting that
      the transcriptional activator heat shock factor 1 (HSF-1) regulates stress
      resistance genes that extend longevity independently of DAF-16. They also show
      that overexpression of HSF-1 in neurons or body-wall muscle cells is sufficient
      to extend longevity. The role of multiple transcription factors in extending life
      span in yeast and worms raises the possibility that many transcriptional
      regulators can contribute to longevity extension.

PMID- 14960762
TI  - The magic human 46 chromosomes were immortalised on a bronze plaque at Lund
      University in Sweden.

PMID- 14960763
TI  - Fungal molecular diagnostics: a mini review.
AB  - Conventional methods to identify fungi have often relied on identification of
      disease symptoms, isolation and culturing of environmental organisms, and
      laboratory identification by morphology and biochemical tests. Although these
      methods are still fundamental there is an increasing move towards molecular
      diagnostics of fungi in all fields. In this review, some of the molecular
      approaches to fungal diagnostics based on polymerase chain reaction (PCR) and
      DNA/RNA probe technology are discussed. This includes several technological
      advances in PCR-based methods for the detection, identification and
      quantification of fungi including real-time PCR which has been successfully used
      to provide rapid, quantitative data on fungal species from environmental samples.
      PCR and probe based methods have provided new tools for the enumeration of fungal
      species, but it is still necessary to combine the new technology with more
      conventional methods to gain a fuller understanding of interactions occurring in
      the environment. Since its introduction in the mid 1980's PCR has provided many
      molecular diagnostic tools, some of which are discussed within this review, and
      with the advances in micro-array technology and real-time PCR methods the future
      is bright for the development of accurate, quantitative diagnostic tools that can
      provide information not only on individual fungal species but also on whole
      communities.

PMID- 14960764
TI  - Cloning a DNA marker associated to wheat scab resistance.
AB  - Wheat head blight caused mainly by Fusarium graminearum, is an important wheat
      disease, causing yield and quality losses. The breeding of resistant varieties is
      the key measure to control this disease, but the conventional breeding method is
      of low efficiency. The marker-assisted selection (MAS) can significantly improve
      the breeding efficiency. In this study, four RAPD (randomly amplified polymorphic
      DNA) markers linked to FHB resistance were obtained and one was cloned and
      sequenced. F7 recombinant inbred lines (RILs) were derived from the F1 of the
      cross Ning894037 (resistant)/Alondra (susceptible) by the single-seed descent
      method. Scab resistance of F7 RILs was evaluated in the greenhouse by injecting
      conidiospores into a central floret. Scab symptoms were evaluated on the 21st day
      after inoculation. Disease severity was assessed as the percentage of infected
      spikelets/spike. The F7 RIL population displayed a normal distribution,
      transgressive segregation and significant variation for FHB severity. DNA from
      resistant and susceptible parents was analyzed with 520 RAPD primers. Four
      markers (S1384-640,S1360-600, S1319-350,S1319-820) linked to FHB resistance were
      obtained. DNA of S1384-640 was recovered, subjected to re-amplification by using
      S1384 primer and the same protocol as for RAPD analysis and identified the
      rightness. The PCR product of S1384-640 was ligated into the pUCm-T vector, and
      cloned into fresh competent cells of Escherichia coli strain DH5alpha RAPD
      analysis showed that the inserts of the recombinant plasmids were DNA of S1384
      640. The sequencing result showed that the cloned fragment was 648 bp.

PMID- 14960765
TI  - Numerical method for detection of linkage between genes for two metrical traits.
AB  - A homozygous population derived from hybrids between two homozygous parents may
      be used for genetic analysis of metrical traits. The paper describes the use of
      doubled haploids (DH) and single seed descent (SSD) lines for detection of
      linkage between genes conditioning two quantitative traits. A computational
      algorithm is presented, which facilitates matching various variants of relations
      between variances, covariances and means of DH and SSD populations so as to make
      it possible to conclude on the presence/absence of linkage. The suggested
      methodology is illustrated with an example concerning three quantitative traits
      of barley: length of the third internode, stem wall thickness, and 1000-grain
      weight.

PMID- 14960766
TI  - Intensification of lipase biosynthesis as a result of electrofusion of Rhizopus
      cohnii protoplasts.
AB  - Our objective was to obtain products of fusion of the filamentous fungus Rhizopus
      cohnii Rh.c./1 with an increased capacity for lipase biosynthesis in comparison
      with the original strain. Protoplasts of auxotrophic mutants of the parent strain
      Rh.c./1 obtained after UV irradiation of the spores were subjected to
      electrofusion. We found that the largest number of electrofusion products could
      be obtained with the use of the following process parameters: 1 or 2 impulses
      immediately following one another with a field intensity of 200 V/cm and an
      exposition time of 1000 ms at the stage of dielectrophoresis, 1 impulse with a
      field intensity of 500 V/cm and an exposition time of 10 ms or 20 ms at the stage
      of fusion, regulated temperature of 4 degrees C before and after the process,
      rounding time of ca 20 min. Electrofusion of protoplasts of auxotrophic mutants
      of the Rh.c./1 strain produced 19 fusion products whose lipase biosynthesis
      capacity in a liquid medium culture was higher than that of the parent strains.
      The fusion product labelled XIII-21 was selected as the best strain. Lipase
      activity obtained after its culture in the liquid medium was ca 3.5 times higher
      than that obtained after the culture of the original strain Rh.c./1.

PMID- 14960767
TI  - Correlations and heritability of the characters determining the seed yield of the
      long-raceme alfalfa (Medicago sativa L.).
AB  - Phenotypic correlation coefficients and heritability of the characters
      controlling seed yield of long-raceme forms of alfalfa was determined. It was
      found that seed yield per plant, which was positively correlated with 10 out of
      12 analysed characters, depended upon the number of pods per raceme and the
      number of seeds per pod. Variability of these characters determined about 60% of
      the variability of seed yield. Multiple linear regression and phenotypic
      correlations show that simultaneous selection for increased pod number per raceme
      and increased seed number per pod and raceme length resulted in enhanced seed
      yield potential. The share of the additive genetic effects in the phenotypic
      variance for number of pods per raceme was low and about 21-23%, while for number
      of seeds per pod and per raceme amounted to about 50%. The expected genetic
      progress in recombination breeding for number of seeds per pod and number of
      seeds per raceme will be of medium magnitude, while one cannot expect any rapid
      and considerable progress in the number of pods per raceme. Considering the high
      positive correlation between raceme length and number of pods and seeds per
      raceme, one should conclude that raceme length can be an important criterion in
      selection of plants showing a high seed productivity.

PMID- 14960768
TI  - Divergent selection for skeletal malformations in chickens alters polymorphism at
      microsatellite loci.
AB  - The objective of this study was to determine microsatellite polymorphism in Rhode
      Island Red (RIR) and Sussex (SX) chickens, divergently selected over six
      generations for high (H) or low (L) incidence of skeletal defects in embryos
      (30.7% for H lines, 3.7% for L lines). The polymorphism analysis covered 15
      microsatellite markers within four lines (a total of 60 individuals). Eight
      alleles were identified as specific to H lines and six alleles as specific to L
      lines. The selection for skeletal malformation appears to have affected the
      frequency of microsatellite alleles. The experimental material examined
      constitutes a valuable source for identification of real genes causing skeletal
      defects.

PMID- 14960769
TI  - Silent point mutation polymorphism of the bovine CD18 encoding gene.
AB  - We report on a PCR-RFLP procedure for recognising of a silent point mutation of
      ITGB2 CD18 subunit gene in cattle. Polymorphism screening was performed in a
      Polish Black-and-White cattle population (n=210). The genotype and allele
      frequencies were established in the sires and cows. Further research is needed to
      explain the possible applications of the CD18 silent point mutation as a
      potential molecular marker for high milk productivity.

PMID- 14960770
TI  - Genetic background of cutaneous forms of lupus erythematosus: update on current
      evidence.
AB  - This article reviews and updates current information on the possible genetic
      basis for cutaneous lupus erythematosus. The aetiology of this condition remains
      unknown and is believed to be multifactorial, involving genetic, environmental
      and retroviral factors. A genetic predisposition is probably the greatest risk
      factor for this condition. Individual susceptibility to lupus erythematosus may
      be determined by a combination of specific polymorphisms of genes encoding
      multiple cytokines, adhesion molecules, and cellular proteins. This condition may
      lead to an abnormal expression of immunoregulatory molecules and finally results
      in the development or exacerbation of the disease. Recently also the role of
      endogenous retroviral sequences in the pathogenesis of autoimmunity has been
      discussed.

PMID- 14960771
TI  - STR polymorphisms in Philippine ethnolinguistic groups: evaluation of forensic
      utility.
AB  - Population data was collected for the STR loci F13AO1, FES/FPS, HUMvWA, and
      HUMTHO1, in three major Philippine ethnolinguistic groups and used to estimate
      statistical parameters for identity testing in forensic work on Filipinos. The
      Cebuano, Ilocano, and Pampango populations in the Philippines were studied
      because they are among the biggest linguistic groups in the country, thus their
      genotypic profiles should substantially represent those of many Filipinos. The
      number of alleles varied from 4 to 9 at all loci, falling within the range
      observed for other local and world populations. Pairwise comparisons of the
      allele frequency distributions showed no statistical differences among the
      populations. The test for linkage equilibrium showed no evidence of non-random
      association of alleles across the physically unlinked loci in any of the three
      populations. The four loci combined gave an exclusion power of > or =0.9995 and a
      power of paternity exclusion of 0.8859-0.9389.

PMID- 14960772
TI  - Molecular genetic analysis of the GJB1 gene: a study of six mutations.
AB  - Charcot-Marie-Tooth type X1 disease (CMTX1) is an X-dominant peripheral
      neuropathy caused by mutations in the GJB1 gene. Molecular genetic analysis of
      the GJB1 gene is crucial for CMTX1 diagnosis and for genetic counselling. To
      date, molecular genetic analysis of the GJB1 gene revealed 264 mutations in the
      GJB1 gene. In spite of the rising number of GJB1 gene mutations, family history
      was documented in only a few CMTX1 cases. The aim of this study was a molecular
      genetic analysis of the GJB1 gene in 7 families, performed in 19 CMTX1-affected
      patients and 13 healthy family members. Moreover, we attempted to report evidence
      of effects of 6 amino-acid substitutions described in this study. To the best of
      our knowledge, the G110D, V152D and K167E mutations are novel substitutions,
      which have not been reported so far.

PMID- 14960773
TI  - Polymorphism of trinucleotide repeats in non-translated regions of SCA8 and SCA12
      genes: allele distribution in a Polish control group.
AB  - Spinocerebellar ataxias are a group of neurodegenerative disorders caused by
      dynamic mutations of microsatellite repeats. Two novel forms of SCAs have been
      described recently: SCA8, with expansions of CTA/CTG repeats in 3'UTR of the SCA8
      gene, and SCA12, caused by expansion of the CAG tract in 5'UTR of the
      SCA12/PP2R2B gene. Analysis of CTA/CTG and CAG polymorphism in those two genes
      was performed in a Polish control group consisting of 100 individuals without any
      neurological signs. The distribution and ranges of the number of non-pathogenic
      repeats were similar to those observed in other populations described previously.
      Expansion of CTA/CTG repeats in the SCA8 locus was found in 2 of 100 controls and
      in 5 probands among 150 pedigrees affected with unidentified ataxias. As such
      expanded alleles were also observed in their healthy relatives, the pathogenic
      role of expansions in the SCA8 gene remains uncertain.

PMID- 14960774
TI  - Apparent X-linked primary ciliary dyskinesia associated with retinitis pigmentosa
      and a hearing loss.
AB  - Three brothers, one 10-year-old and a pair of 14-year-old dizygotic twins-
      expressed the classical, early-onset retinitis pigmentosa (RP) with typical
      ophthalmoscopic findings, night blindness, visual field constricted to 10 degrees
      and flat ERG response. All three brothers were also diagnosed with primary
      ciliary dyskinesia (PCD) and had recurrent respiratory infections, chronic
      sinusitis and bronchiectasis. In all of them, resection of the middle lobe of the
      right lung was performed. A similar clinical picture of coexisting RP and PCD was
      noted in the brother of the probands' mother. All probands displayed situs
      solitus. Consistent with the X-linked mode of RP inheritance, there were also
      three obligatory female carriers of the disorder in this family: the mother of
      the affected boys, her mother and a daughter of her brother. In all of them,
      retinitis pigmentosa "sine pigmento" was found with milder but clinically
      significant symptoms (mild night blindness, visual field constricted to 30
      degrees, and scotopic and photopic ERG responses reduced to 30-60%). No
      extraocular symptoms were detected in any of the heterozygous female carriers.
      This family presents an example of two rare phenomena: X-linked dominant
      retinitis pigmentosa (with milder expression in females) and a rare combination
      of RP with recurrent respiratory infections due to PCD.

PMID- 14960775
TI  - Bacteriophage contamination: is there a simple method to reduce its deleterious
      effects in laboratory cultures and biotechnological factories?
AB  - Infection of bacterial cultures by bacteriophages as well as prophage induction
      in the host cells are serious problems in both research and biotechnological
      laboratories. Generally, prevention strategies (like good laboratory/factory
      hygiene, sterilisation, decontamination and disinfection) are necessary to avoid
      bacteriophage contamination. However, it is well known that no matter how good
      the laboratory/factory practice and hygiene are, bacteriophage infections occur
      from time to time. The use of immunised or resistant bacterial strains against
      specific phages may be helpful, but properties of the genetically modified
      strains resistant to phages are often worse (from the point of view of a
      researcher or a biotechnological company) than those of the parental, phage
      sensitive strains. In this article we review recent results that may provide a
      simple way to minimise deleterious effects of bacteriophage infection and
      prophage induction. It appears that low bacterial growth rates result in a
      significant inhibition of lytic development of various bacteriophages. Moreover,
      spontaneous prophage induction is less frequent in slowly growing bacteria.

PMID- 14960776
TI  - Small-gap insertion-device development at the National Synchrotron Light Source-
      performance of the new X13 mini-gap undulator.
AB  - The National Synchrotron Light Source (NSLS) 2.8 GeV electron storage ring
      continues to set high standards in insertion-device research and development. The
      Chasman-Green NSLS lattice design provides for dispersion-free long straight
      sections in addition to a very small vertical beta function. As the electron beam
      size is proportional to the square root of this function, a program to exploit
      this feature was undertaken more than a decade ago by implementing short-period
      small-gap insertion devices in the NSLS storage ring. The possibility of
      utilizing existing moderate-energy synchrotron radiation electron storage rings
      to produce high-brightness photon beams into the harder X-ray region have been
      realised using in-vacuum undulators. In this article the operation of a 1.25 cm
      period mini-gap undulator, operating down to a gap of 3.3 mm within the NSLS X13
      straight section, is reported. It is the brightest source of hard X-rays in the
      energy range approximately 3.7-16 keV at the NSLS, and replaces an in-vacuum
      undulator which had a more limited tunability.

PMID- 14960777
TI  - Performance of a cryogenic silicon monochromator under extreme heat load.
AB  - The performance of an indirectly cooled cryogenic silicon monochromator under
      heat loads up to 870 W has been studied. The investigation was performed over
      numerous parameters and included measurements of total flux, spectral density,
      rocking curves, angular beam profiles and crystal slope errors. An almost ideal
      monochromator performance was observed in the 270-570 W range of the heating
      power. At a heat load of approximately 400 W and under standard operation
      conditions, the crystal distortions did not exceed 1 micro rad. At the highest
      available heat load of 870 W, the crystal distortions were about 7 micro rad.

PMID- 14960778
TI  - CD12: a new high-flux beamline for ultraviolet and vacuum-ultraviolet circular
      dichroism on the SRS, Daresbury.
AB  - This paper describes the commissioning and characterization of an SRS bending
      magnet beamline constructed for the measurement of vacuum-ultraviolet circular
      dichroism on biological and other materials. The beamline provides photon fluxes
      of many orders of magnitude greater than commercial instruments or beamlines at
      other synchrotron radiation facilities. The beamline uses the conventional
      approach of utilizing the plane polarized light emitted from the bending magnet
      which is subsequently converted into circularly polarized light using a
      photoelastic modulator with a switching frequency of 50 kHz. The beamline has a
      best wavelength resolution of 0.5 nm and stray light levels better than 0.01%.
      The latter may be predicted to give improved performance over other beamlines at
      synchrotron radiation sources especially when short-wavelength CD spectra are to
      be collected. An example spectrum and submillisecond time-resolved CD profile are
      given and the impact that the new beamline is likely to have is speculated on.
      The ultimate flux limitations of the technique with regard to the avoidance of
      the effects of radiation damage are also discussed.

PMID- 14960779
TI  - Combining flat crystals, bent crystals and compound refractive lenses for high
      energy X-ray optics.
AB  - Compound refractive lenses (CRLs) are effective for collimating or focusing high
      energy X-ray beams (50-100 keV) and can be used in conjunction with crystal
      optics in a variety of configurations, as demonstrated at the 1-ID undulator
      beamline of the Advanced Photon Source. As a primary example, this article
      describes the quadrupling of the output flux when a collimating CRL, composed of
      cylindrical holes in aluminium, is inserted between two successive
      monochromators, i.e. a modest-energy-resolution premonochromator followed by a
      high-resolution monochromator. The premonochromator is a cryogenically cooled
      divergence-preserving bent double-Laue Si(111) crystal device delivering an
      energy width DeltaE/E approximately 10(-3), which is sufficient for most
      experiments. The high-resolution monochromator is a four-reflection flat Si(111)
      crystal system resembling two channel-cuts in a dispersive arrangement, reducing
      the bandwidth to less than 10(-4), as required for some applications. Tests with
      67 and 81 keV photon energies show that the high-resolution monochromator, having
      a narrow angular acceptance of a few microradians, exhibits a fourfold throughput
      enhancement due to the insertion of a CRL that reduces the premonochromatized
      beam's vertical divergence from 29 micro rad to a few microradians. The ability
      to focus high-energy X-rays with CRLs having long focal lengths (tens of meters)
      is also shown by creating a line focus of 70-90 micro m beam height in the
      beamline end-station with both the modest-energy-resolution and the high-energy
      resolution monochromatic X-rays.

PMID- 14960780
TI  - Ray-tracing analysis of diffractive-refractive X-ray optics.
AB  - Ray-tracing simulations of mistuned sagittal diffractive-refractive X-ray lenses
      (DRXL) are presented. In this article, firstly the characteristic aberrations for
      various types of crystal misalignments within one-crystal and four-crystal DRXLs
      are considered, and the sensitivity of such an optical system to the mutual
      misalignment of its components is discussed. The simulations reveal that a DRXL
      is not too sensitive to the adjustment of its components. In the second part of
      this article the performance of such lenses with ideal and approximate profiles
      is examined. Comparative analysis of parabolic and cylindrical DRXLs showed that,
      in the case when the linear source size is comparable with the acceptance of the
      lens, the performances of parabolic and cylindrical DRXLs are practically the
      same.

PMID- 14960781
TI  - The new materials processing beamline at the SRS Daresbury, MPW6.2.
AB  - A new beamline (MPW6.2) has been designed and built for the study of materials
      during processing where three synchrotron techniques, SAXS, WAXS and XAS, are
      available simultaneously. It has been demonstrated that Rietveld refinable data
      can be collected from silicon SRM 640b over a 60 degrees range in a time scale of
      1 s. The data have been refined to a chi(2) of 2.4, the peaks fitting best to a
      Pearson VII function or with fundamental parameters. The peak halfwidths have
      been found to be approximately constant at 0.06 degrees over a 120 degrees
      angular range indicating that the instrumental resolution function has matched
      its design specification. A quantitative comparison of data sets collected on the
      same isotactic polypropylene system on MPW6.2 and DUBBLE at the ESRF shows a 17%
      improvement in angular resolution and a 1.8 improvement in peak-to-background
      ratio with the RAPID2 system; the ESRF data vary more smoothly across detector
      channels. The time-dependent wide-angle XRD was tested by comparing a hydration
      reaction of gypsum-bassanite-anhydrite with energy-dispersive data collected on
      the same system on the same time scale. Three sample data sets from the reaction
      were selected for analysis and gave an average chi(2) of 3.8. The Rietveld
      refined lattice parameters are a good match with published values and the
      corresponding errors show a mean value of 3.3 x 10(-4). The data have also been
      analysed by the Pawley decomposition phase-modelling technique demonstrating the
      ability of the station to quickly and accurately identify new phases. The
      combined SAXS/WAXS capability of the station was tested with the crystallization
      and spinodal decomposition of a very dilute polymer system. Our measurements show
      that the crystallization of a high-density co-polymer (E76B38) as low as 0.5% by
      weight can be observed in solution in hexane. The WAXS and SAXS data sets were
      collected on the same time scale. The SAXS detector was calibrated using a
      collagen sample that gave 30 orders of diffraction in 1 s of data collection. The
      combined XRD and XAS measurement capability of the station was tested by
      observing the collapse and re-crystallization of zinc-exchanged zeolite A
      (zeolite Zn/Na-A). Previous studies of this material on station 9.3 at the SRS
      were compared with those from the new station. A time improvement of 38 was
      observed with better quality counting statistics. The improved angular resolution
      from the WAXS detector enabled new peaks to be identified.

PMID- 14960782
TI  - Design of a variable-included-angle Monk-Gillieson monochromator with varied-line
      spacing gratings.
AB  - A novel design concept is presented for a variable-included-angle Monk-Gillieson
      mounting monochromator with a varied-line-spacing (VLS) plane grating, in which
      the grating is illuminated by converging X-rays. The energy resolution for a
      beamline with a typical undulator source is estimated by means of the ray-tracing
      method. It is shown that the source-size or slope-error limited resolution is
      achieved in a wide energy range by properly changing the included angle.
      Moreover, relatively high resolution is maintained even if one scans the photon
      energy with a fixed included angle, which is a great advantage over the previous
      VLS grating monochromator with diverging illumination on the grating. A design
      example for a bending-magnet beamline is also presented, indicating that the new
      design concept is valid even for high-emittance sources.

PMID- 14960783
TI  - Development of a two-dimensional virtual-pixel X-ray imaging detector for time
      resolved structure research.
AB  - An interpolating two-dimensional X-ray imaging detector based on a single-photon
      counter with gas amplification by GEM (gas electron multiplier) structures is
      presented. The detector system can be used for time-resolved structure research
      down to the micro s time domain. The prototype detector has been tested at the
      SAXS (small-angle X-ray scattering) beamline at ELETTRA synchrotron light source
      with a beam energy of 8 keV. The imaging performance is examined with apertures
      and standard diffraction targets. Finally, the application in a time-resolved
      lipid temperature-jump experiment is presented.

PMID- 14960784
TI  - Observation of divergent-beam X-ray diffraction from a crystal of diamond using
      synchrotron radiation.
AB  - In 1947 Kathleen Lonsdale conducted a series of experiments on X-ray diffraction
      using a divergent beam external to a crystal sample. Unlike the Kossel technique,
      where divergent X-rays are excited by the presence of fluorescing atoms within
      the crystal, the use of an external divergent source made it possible to study
      non-fluorescing crystals. The resulting photographs not only illustrated the
      complexity of X-ray diffraction from crystals in a truly beautiful way, but also
      demonstrated unprecedented experimental precision. This long-forgotten work is
      repeated here using a synchrotron radiation source and, once again, considerable
      merit is found in Lonsdale's technique. The results of this experiment suggest
      that, through the use of modern 'third-generation' synchrotron sources, divergent
      beam diffraction could soon enjoy a renaissance for high-precision lattice
      parameter determination and the study of crystal perfection.

PMID- 14960785
TI  - Pinhole interferometry with coherent hard X-rays.
AB  - This paper discusses the experimental realisation of two types of X-ray
      interferometer based on pinhole diffraction. In both interferometers the beam
      splitter was a thin metal foil containing micrometer pinholes to divide the
      incident X-ray wave into two coherent waves. The interference pattern was studied
      using an energy-dispersive detector to simultaneously investigate in a large
      spectral range the diffraction properties of the white synchrotron radiation. For
      a highly absorbing pinhole mask the interference fringes from the classical
      Young's double-pinhole experiment were recorded and the degree of coherence of X
      rays could be determined. In the case of low absorption of the metal foil at
      higher X-ray energies (>15 keV) the interference pattern of a point diffraction
      interferometer was observed using the same set-up. The spectral refraction index
      of the metal foil was determined.

PMID- 14960786
TI  - XAFS study of americium sorbed onto groundwater colloids.
AB  - The sorption of americium, as Am(III), onto groundwater colloids obtained from a
      marl aquifer was studied in 2 x 10(-2)M sodium bicarbonate groundwater and 2 x
      10(-2)M sodium chloride bicarbonate-free solutions. At the in situ groundwater pH
      of 8.6, the americium was strongly sorbed onto the colloids. XAFS analyses were
      performed on these sorbed Am species to establish the oxidation state and its
      near-neighbour bonding. These XAFS data, obtained at 400 mg l(-1) colloid
      concentrations and total Am concentration of 1.53 x 10(-5)M (dissolved and onto
      colloids), indicated that Am remains trivalent, and that surface complexes are
      formed with the colloids without surface precipitation. This conclusion is based
      on the absence of Am-Am interactions in the second or third shells. The surface
      complexes generated by the Am(III) sorbed onto active sites are described on the
      basis of the XAFS data. They include the presence of about seven water molecules
      around the ternary surface complexes of this trivalent actinide.

PMID- 14960787
TI  - A versatile rapid-mixing and flow device for X-ray absorption spectroscopy.
AB  - A low-temperature rapid-mixing and flow system has been designed and implemented
      to monitor catalysis involving metal ions by X-ray absorption spectroscopy at the
      ID-18 beamline of the Advanced Photon Source, Argonne National Laboratory. The
      system will allow examination of biological metallo-intermediates at dilute metal
      ion concentrations by the detection of X-ray fluorescence. The instrument can be
      cooled to sub-zero temperatures, thus lengthening the life time of a reaction
      intermediate. A portable UV-visible spectrometer is integrated with the flow
      system to monitor the sample optically. The system can also be used as a
      continuous-flow device to minimize radiation-induced sample damage by reducing
      sample exposure to the X-ray beam. The integration of the stop-flow instrument
      with the synchrotron beamline and X-ray fluorescence detector systems makes it
      unique for time-resolved X-ray absorption studies of dilute biological reactions.
      The results of the initial testing of the system are presented.

PMID- 14960788
TI  - XAFS imaging of Tsukuba gabbroic rocks: area analysis of chemical composition and
      local structure.
AB  - Gabbroic rocks were collected at Mount Tsukuba in Japan, and their XAFS images
      were studied using a projection-type X-ray fluorescence (XRF) microscope, which
      is a powerful new tool recently developed for extremely rapid imaging. The
      instrument employs a grazing-incidence arrangement in order that primary X-rays
      illuminate the whole sample surface, as well as parallel-beam optics and an
      extremely close geometry in order to detect XRF by a high-performance X-ray CCD
      system with 1024 x 1024 pixels. The XRF image indicated that black amphibole and
      white feldspar, both of which are typical mineral textures of the rock, contain
      iron. The origin has been suggested to be several small yellowish-brown minerals
      contained there. The XAFS imaging has been carried out by repeating the exposure
      of XRF images during the energy scan of the primary X-rays. It has been found
      that the structure is qualitatively close to that of olivine, and the main
      differences found in both areas can be explained as a difference in iron and
      magnesium concentration, i.e. the mixed ratio of forsterite (Mg(2)SiO(4)) and
      fayalite (Fe(2)SiO(4)). The feasibility of the present XAFS imaging method has
      been demonstrated for realistic inhomogeneous minerals.

PMID- 14960789
TI  - Canadian Light Source starts.

PMID- 14960790
TI  - SPEAR3--a 3 GeV third-generation synchrotron radiation source at Stanford.

PMID- 14960795
TI  - Evaluation of serum steroid hormones in schizophrenic patients.
AB  - BACKGROUND: Recent studies have implicated the abnormalities in the gamma
      aminobutyric acid (GABA) neurotransmmiter system in the pathophysiology of
      schizophrenia. There are also evidences indicating that steroids of central or
      peripheral origin may modulate GABAergic system through direct interaction with
      the GABAA receptor complex. These raise the possibility that alternations in
      serum steroid hormones may contribute to the pathophysiological process in the
      schizophrenia. AIMS: The purposes of this study were first, to determine whether
      alternations in steroid serum levels occur in schizophrenic patients, and
      secondly to determine whether such alternations normalize with clinical
      improvement. METHODS AND MATERIAL: Serum concentrations of testosterone (T),
      estradiol (E), progesterone (P) and cortisol (C) were determined in male
      schizophrenic patients (N = 49) before treatment, during treatment and after
      recovery and in age-matched healthy male subjects (N = 17). All steroid hormones
      were assayed by ELISA method. STATISTICAL ANALYSIS USED: Differences in steroids
      concentrations between groups were assayed by One-Way Analysis of Variance
      (ANOVA), followed by Tukey's post hoc test. The level of significance was
      considered at P < 0.05. RESULTS AND CONCLUSION: The serum concentrations of E, P
      and C were significantly (P < 0.05) lower in male schizophrenic patients in all
      three stages of the study, compared with healthy subjects. Serum concentrations
      of T were significantly (P < 0.05) lower in male schizophrenic patients before
      and during treatment, but not after recovery, compared with healthy subjects.
      These findings support the occurrence of abnormal steroid concentrations in
      schizophrenic patients and suggest that lower T level in this disorder is related
      to the illness and normalizes with remission, while trait-related factors may
      contribute to lower serum E and C levels in schizophrenia.

PMID- 14960796
TI  - Bacteriological and antimicrobial susceptibility profile of soft tissue
      infections from Northern India.
AB  - BACKGROUND: Soft tissue infections require a judicious combination of
      antimicrobial therapy in addition to surgical debridement to limit tissue loss
      and preserve life. AIMS: To study the bacterial etiology of soft tissue
      infections and their antimicrobial susceptibility pattern. SETTINGS AND DESIGN: A
      single institutional retrospective study of one year duration from January to
      December 2002. MATERIALS AND METHODS: A total of 5039 consecutive pus samples
      received in the Bacteriology Laboratory was analyzed from the records. RESULTS:
      There were a total of 2783 bacterial isolates comprising of 1504 gram negative
      bacilli and 1279 gram positive cocci. Staphylococcus aureus was the commonest
      isolate followed by Escherichia coli and Pseudomonas species. Methicillin
      resistance in S. aureus was found to be 38.56%, high level aminoglycoside
      resistance was observed in 53.3% enterococci and 66.75% of the gram negative
      bacilli were extended spectrum beta-lactamase producers. Rifampicin and
      vancomycin showed best activity for S. aureus; for gram-negative bacilli,
      piperacillin-tazobactam combination showed best activity. CONCLUSIONS: Continuous
      monitoring of antimicrobial susceptibility pattern in individual settings
      together with their judicious use is emphasized to minimize emergence of drug
      resistant bacteria.

PMID- 14960797
TI  - Reduced minimum inhibitory concentration of chloramphenicol for Salmonella
      enterica serovar typhi.
AB  - BACKGROUND: Ciprofloxacin replaced chloramphenicol (C), the best choice of
      antibiotic in the treatment of enteric fever, when C-resistant enteric fever
      emerged and caused outbreaks in different parts of the world. C-sensitive S.
      enterica serovar Typhi emerged again due to withdrawal of the antibiotic
      pressure. AIMS: To assess the in vitro efficacy of C against Salmonella enterica
      serovar Typhi isolates (1991-2003). MATERIAL AND METHODS: A total of 464 blood
      culture isolates of S. enterica serovar Typhi were subjected to C susceptibility
      by disc diffusion and agar dilution methods using Mueller-Hinton agar. The
      antibiotic susceptibility of S. enterica serovar Typhi isolates obtained in the
      year 2002 and 2003 was determined using ampicillin, cotrimoxazole, ciprofloxacin,
      nalidixic acid, ceftriaxone and cefotaxime, in addition to C. Escherichia coli
      strain ATCC 25922 was used as the control. Changes in C sensitivity of the
      isolates were analyzed using chi2 test with Yates correction. RESULTS AND
      CONCLUSIONS: All the isolates of 1991 were C-resistant with minimum inhibitory
      concentration values (MICs) of 2000-5000 mg/ml. In the following years decrease
      in frequency of C resistance was noticed: 1992 (50%), 1993 (32%), 1994 (27%) and
      1995 (05%). The isolates of 1996-99 and 2001 were 100% C-sensitive. In 2000,
      sensitivity was also high (79%). The strains isolated in the year 2002 and 2003,
      showing reduced susceptibility of ciprofloxacin, were nalidixic acid resistant,
      but sensitive to the third-generation cephalosporins (ceftriaxone and
      cefotaxime). The MICs for C-sensitive isolates (1991-2003) ranged 0.1-5 mg/ml.
      Results suggest the necessity for re-evaluation of C therapy in typhoid fever.

PMID- 14960798
TI  - Anemia.

PMID- 14960799
TI  - Approach to a patient with anemia.

PMID- 14960800
TI  - Analysis of cell fate specification during ascidian early embryogenesis.

PMID- 14960801
TI  - Growth hormone and prolactin in environmental adaptation.

PMID- 14960802
TI  - Mechanism of chemotaxis of the ascidian spermatozoa.

PMID- 14960803
TI  - Proportion and cluster analyses of the skull in various species of the tree
      shrews.
AB  - The skull adaptation was functional-morphologically examined in 14 species of the
      tree shrews. From the data of the proportion indices, the similarities were
      confirmed between T. minor and T. gracilis, T. tana and T. dorsalis, and T.
      longipes and T. glis. We demonstrated that the splanchnocranium was elongated in
      terrestrial T. tana and T. dorsalis and shortened in arboreal T. minor and T.
      gracilis from the proportion data. In both dendrogram from the matrix of the Q
      mode correlation coefficients and scattergram from the canonical discriminant
      analysis, the morphological similarities in the skull shape suggested the
      terrestrial-insectivorous adaptation of T. tana and T. dorsalis, and the arboreal
      adaptation of T. minor and T. gracilis. Since the osteometrical skull
      similarities were indicated among the three species of Tupaia by cluster and
      canonical discriminant analyses, the arbo-terrestrial behavior and its functional
      morphological adaptation may be commonly established in T. montana, T. longipes
      and T. glis.

PMID- 14960804
TI  - Isolation and expression of five-amino-acid-deleted variant of feline hepatocyte
      growth factor (HGF) cDNA.
AB  - Hepatocyte growth factor (HGF) is a pleiotropic cytokine that stimulates a wide
      array of cellular targets, including hepatocytes and other epithelial cells,
      melanocytes, endothelial and hematopoietic cells. We have cloned a different form
      of cDNA, with a deletion of 15 base pairs predicted to result in the loss of 5
      amino acids from the first kringle domain. To investigate the biological
      activity, original and deleted variant of feline HGF cDNAs were transiently
      expressed in COS-7 cells. Both recombinant feline HGFs showed almost the same
      dose-response curves in the stimulation of the growth of BNL CL.2 cells (a mouse
      hepatocyte cell line) and scatter activity of Madin-Darby canine kidney (MDCK)
      cells. The findings reported here suggest that the deleted variant of feline HGF
      has almost the same biological activity as the original in terms of the
      proliferation and scatter activity.

PMID- 14960805
TI  - Analysis of a full-length cDNA library constructed from swine olfactory bulb for
      elucidation of expressed genes and their transcription initiation sites.
AB  - The olfactory system is indispensable to the survival of animals in finding foods
      and for the reproductive process. Odorant signals are conveyed through olfactory
      sensory neurons to the olfactory bulb, which modifies the signals and relays them
      to the neocortex. In the present study, a "full-length" cDNA library was
      constructed from the main and accessory olfactory bulbs of 5-week-old male pigs,
      in order to elucidate the expressed genes. The average insert size of the library
      was estimated to be 1.7 kb based on 54 randomly-selected clones. One thousand
      randomly selected clones were subjected to sequencing, and the resulting 883
      sequences were then clustered into 753 sequences based on similarity. Since 723
      of the 753 sequences had sufficient sequence information for homology analysis,
      the 723 sequences were subjected to BLAST analysis against GenBank/EMBL/DDBJ; 655
      out of the 723 sequences showed similarities with known genes, and the remaining
      68 were indicated to be novel sequences. The full-length rate of the library was
      estimated to be ca. 80%, using 70 sequences corresponding to human full-length
      cDNAs. The full-length cDNA sequences of a single gene appearing more than 6
      times in the analysis were aligned to determine major transcription initiation
      sites for SLC25A, CKB, TUBB4, TUBB, YWHAH, TUBB2, and CNP genes.

PMID- 14960806
TI  - Immunological findings in 3 dogs clinically diagnosed with allergic rhinitis.
AB  - Three dogs clinically diagnosed with allergic rhinitis (AR) were examined for
      their immunological findings. House dust mites (HDM) such as Dermatophagoides
      farinae (DF) and D. pteronyssinus (DP) were identified as positive allergens in
      the 3 dogs with both intradermal skin test and serum antigen-specific IgE test.
      Lymphocyte blastogenic response of peripheral blood mononuclear cells (PBMCs)
      under stimulation with DF antigen in dogs with AR was higher than that in 4
      healthy control dogs. Expression level of IL-4 mRNA in PBMCs obtained from the 3
      AR dogs was higher than that in PBMCs obtained from 4 healthy control dogs before
      and after stimulation with DF antigen. Expression level of IFN-gamma mRNA in
      PBMCs was not different between the AR and control dogs before and after
      stimulation with DF antigen. These results suggested that allergic reaction to
      HDM antigen and T(H)2-type immune response were associated with the development
      of AR in 3 dogs examined in this study.

PMID- 14960807
TI  - Effect of active immunization of pony mares against recombinant porcine inhibin
      alpha subunit on ovarian follicular development and plasma steroids and
      gonadotropins.
AB  - Two pony mares were immunized against recombinant porcine inhibin alpha subunit
      three times with 39 day intervals. Clinical findings and endocrinological changes
      before immunization were taken as the control. The first significant rise in the
      anti-inhibin titre (P<0.05) in the circulation was found 27 days after the first
      injection. Maximum binding activity was reached by the 12th day after the second
      booster dose. The number of small, medium and large sized follicles had increased
      significantly compared to before immunization (11.75 +/- 4.30, 2.75 +/- 0.69 and
      2.51 +/- 0.63 vs 6.50 +/- 1.43, 1.83 +/- 0.44 and 1.33 +/- 0.38, respectively),
      but the ovulation rate remained unchanged after immunization. The average plasma
      concentration of FSH and estradiol-17beta during the estrous cycle increased
      significantly (P<0.05) after immunization. These results suggest that
      immunization against inhibin is a useful tool to increase the number of ovarian
      follicles during the estrous cycle of pony mares. Moreover, the present study
      supported the concept that inhibin plays a major role in the control of
      follicular growth through its inhibitory effect on FSH secretion synergistically
      with steroid hormones.

PMID- 14960808
TI  - Artificial insemination of frozen epididymal sperm in beagle dogs.
AB  - Freeze-storage of epididymal sperm is an important technique for the preservation
      of gametes in animals, including those becoming extinct. We froze canine sperm
      recovered from the cauda epididymis and investigated the fertility. The qualities
      of sperm from the cauda epididymis before freezing were: mean sperm motility,
      89.4 +/- 1.6 (SE) %; sperm viability, 89.1 +/- 1.1%; and these were significantly
      higher than those of sperm from the caput-corpus epididymis (P<0.01, P<0.05). The
      number of sperm recovered from both cauda epididymides varied among animals: 6.3
      122.3 x 10(7), mean 61.5 +/- 10.0 x 10(7). Freezing was used only for sperm
      recovered from the cauda epididymis. The sperm motility and viability after
      thawing were 19.5 +/- 2.5% and 53.1 +/- 3.3%, respectively. These were slightly
      lower than those of frozen-thawed ejaculated sperm, but the differences were not
      significant. When 2 x 10(8), 3 x 10(8), or 4 x 10 (8) sperm were inseminated in
      the unilateral uterus, only one animal inseminated with 3 x 10(8) sperm was
      fertilized (1/16, 6.3%). When 1 x 10(8) sperm were inseminated in the bilateral
      uterine tubes, one of six animals (16.7%) was fertilized. Therefore, although the
      qualities of epididymal sperm after thawing were similar to those of ejaculated
      sperm, the conception rate obtained with frozen-thawed epididymal sperm was low
      in beagle dogs. It is necessary to investigate the differences in damage between
      epididymal sperm after thawing and ejaculated sperm and to develop a method for
      improving the conception rate.

PMID- 14960809
TI  - Serum haptoglobin concentration in cattle.
AB  - To obtain a basal concentration of serum Haptoglobin (Hp) in cattle in Taiwan, Hp
      concentrations were measured from serum samples collected from 10 healthy
      heifers, every week for one year. The values were also compared with those
      collected from 15 cows diagnosed with postpartum metritis. The heifers were
      successfully impregnated by artificial insemination six months after the tests.
      Hp concentrations were also measured in the serum collected from 11 other cows
      within 3 weeks after parturition. The Hp assay developed in this study gave a
      good correlation (r=0.893)with Western blotting. The Hp concentration of 454
      serum samples from the 10 heifers had a mean value of 83.6 +/- 34.1 mg/l, and
      there was no significant difference among individual heifers. The basal value of
      Hp in heifers was calculated as less than 73.6 mg/l. No significant difference in
      Hp concentration was observed among the 10 heifers during cold and warm seasons
      (19.8 +/- 2.2 degrees C vs 27.3 +/- 1.4 degrees C), or before and after
      pregnancy. The mean serum Hp concentration from cows suffering from postpartum
      reproductive disorders was 1133.5 +/- 627.1 mg/l, which was significantly greater
      than the serum of healthy heifers and postpartum cows (104.6 +/- 61.0 mg/l)
      (P<0.05). These results demonstrate that Hp concentration may be a useful
      indicator for cows with postpartum reproductive disorders.

PMID- 14960810
TI  - Dynamics and histological observation of first follicular wave in Japanese black
      cows.
AB  - AIMS: To determine the turnover of the first follicular wave in Japanese black
      cows and quantitative immunohistological characteristics of the previously in
      vivo identified dominant follicle (DF) and largest subordinate follicle (SF)
      derived from ovariectomy on Day 7 (3 cows) and Day 10 (3 cows) (Day 0=estrus).
      Six cases of first follicular wave in cows were observed twice daily by
      ultrasound scanning. The number of follicles, diameter of DF and SF, and
      prevalence of apoptotic granulosa cells (GC) and theca cells (TC) were studied by
      TUNEL methods. At follicular wave emergence, 13.5 +/- 9.5 Class I (2-5 mm in
      diameter follicles) were found 12 hr after ovulation, and increased its number
      until Day 1 pm. Future DF and SF observed retrospectively were 4.9 +/- 0.8 mm and
      4.9 +/- 0.9 mm at wave emergence. Deviation of DF and SF occurred on Day 3 pm
      with mean diameters of 8.9 +/- 1.3 mm and 6.8 +/- 0.9 mm, respectively. DF
      developed until Day 8 am with a maximum diameter of 14.4 +/- 1.8 mm (n=3) and
      then regressed. The follicular wall of the DF had a characteristic image of a
      healthy follicle on Day 7 and slightly atretic DF on Day 10, whereas SF showed
      heavy atresia on both Day 7 and Day 10 under HE staining. In the prevalence of
      apoptotic cells, DF were 4.4 +/- 1.0% and 17.9 +/- 4.9% on Day 7 and on Day 10 in
      GC, respectively, and 2.4 +/- 0.7% and 8.0 +/- 1.4% on Day 7 and on Day 10 in TC,
      respectively. These results showed that, 1) the first follicular wave in cows is
      characterized by 24 hr recruitment of small follicles and a gradual divergence of
      growth rates in future DF and SF, and 2) early regression of DF on Day 10 was
      preceded by severe apoptosis.

PMID- 14960811
TI  - Role of nitric oxide in hemodialysis-related hypotension in an experimental renal
      dysfunction dog model.
AB  - To clarify the role of nitric oxide (NO) in hemodialysis (HD)-related
      hypotension, the relationship between plasma NO metabolites (NOx) and blood
      pressure changes, and the effect of N(G)-monomethyl-L-arginine (L-NMMA), a NO
      synthase inhibitor, on changes in blood pressure were evaluated in an
      experimental renal dysfunctional dog model. In order to create a renal
      dysfunction model, gentamicin was administered to male beagles in which 7 of 8
      renal artery branches had been ligated. Normal renal functional and dysfunctional
      dogs underwent 3 hr of HD per day for 3 days. HD induced a transient decrease in
      mean blood pressure in the normal renal functional dogs. In renal dysfunctional
      dogs, a continuous hypotension occurred with a gradual increase in the plasma NOx
      concentration during HD. Although L-NMMA prevented the fall in blood pressure, it
      did not significantly change the plasma NOx concentration during HD. These
      results suggest that NO contributes to HD-related hypotension in renal
      dysfunctional dogs but the plasma NOx concentration does not reflect the change
      in blood pressure.

PMID- 14960812
TI  - Blood lipids, fecal fat and chymotrypsin excretion in the dog: influence of age,
      body weight and sex.
AB  - Effects of physiological variables (age, body weight and sex) on lipemia (total
      lipids, phospholipids, triglycerides and NEFA), fecal fat and chymotrypsin
      excretion were examined in dogs. On comparing various ages and body weights, they
      found statistically significant differences, while only total lipids showed a
      statistically significant difference between the two sexes. Moreover, there was a
      significant correlation between body weight and fecal fat and chymotrypsin
      excretion. The results obtained contribute to the evaluation of small intestine
      functionality, especially in relation to some diseases, as malabsorption,
      maldigestion and steatorrhea in the dog.

PMID- 14960813
TI  - Renovation of a drop embryo cultures system by using refined mineral oil and the
      effect of glucose and/or hemoglobin added to a serum-free medium.
AB  - This study was conducted to evaluate whether refining mineral oil and the
      addition of hemoglobin and/or glucose to a serum-free medium could improve in
      vitro-development of embryos cultured in a chemically semi-defined microdroplet
      culture system. Block strain, outbred (ICR) mouse 1- or 2-cell embryos were
      cultured in 5 microl droplets of Chatot, Ziomek and Bavister medium overlaid with
      mineral oil of different types, and preimplantation development to the blastocyst
      stage was subsequently monitored. In the experiment 1, either Sigma (M-8410) or
      BDH (GPR) mineral oil with or without washing was used for embryo culture and,
      distilled water (DW) or culture medium was used as a washing agent. As results,
      better (P<0.0001) development of 1-cell embryos was found in the Sigma than in
      the BDH; more blastocysts developed in Sigma oil washed with culture medium than
      in the others (37% vs. 0%). Subsequently, 1- (experiment 2) or 2-cell (experiment
      3) embryos were cultured in the droplets overlaid with medium-washed Sigma oil,
      to which 0.001 mg/ml hemoglobin and/or 5.6 mM glucose were supplemented at the 1
      cell and the 4-cell stages, respectively. Regardless of embryo stages, blastocyst
      formation was significantly improved by the addition of hemoglobin (54 to 48% vs.
      42 to 31% in 1-cell and 83 to 78% vs. 65 to 68% in 2-cell embryos) and this
      effect was independent of glucose addition. In conclusion, the selection and
      washing of mineral oil, and the addition of hemoglobin is beneficial for
      improving the efficacy of a drop embryo culture system using a serum-free medium.

PMID- 14960814
TI  - Spinal cord effects from lumbar myelographic injection technique in the dog.
AB  - To characterize spinal cord effects of needle placement using lumbar puncture
      myelography technique, lumbar puncture was performed in 5 dogs and computed
      tomography images of the spinal column were acquired in the transverse plane at
      the level of the puncture site after contrast injection and both before and after
      needle removal. The spinal cords were punctured during needle placement and
      parenchymal contrast enhancement was present in 4 of 5 dogs. Although no dogs
      exhibited overt neurological abnormalities following computed tomographic
      imaging, hemorrhage, gliosis and axonal degeneration were confirmed
      microscopically in all subjects. These results suggest that spinal cord morbidity
      is induced when lumbar myelography is performed using currently accepted
      technique.

PMID- 14960815
TI  - Lumbosacral myelography in dogs--a safer technique.
AB  - In search of a safer myelographic technique, we performed myelography via the
      lumbosacral intervertebral space. Eight dogs, in which the backflow of
      cerebrospinal fluid was observed, received contrast media via the lumbosacral
      intervertebral space. The subarachnoid contrast columns were successfully
      observed in 6 dogs. During and after examination, no physiological changes or
      neurological signs were observed. We recommend that the lumbosacral
      intervertebral space be selected first before implementing the conventional
      lumbar myelography.

PMID- 14960816
TI  - Tetralogy of Fallot in a calf: clinical, ultrasonographic, laboratory and
      postmortem findings.
AB  - A 6-month-old female Holstein calf was referred with a history of respiratory
      distress, anorexia and dehydration. When first examined, a loud harsh murmur was
      clearly audible from both sides of the thorax. Two-dimensional echocardiography
      demonstrated a markedly dilated right ventricle and right atrium, hypertrophied
      myocardium, prominent papillary muscles and a thickened interventricular septum
      (IVS). A large-sized ventricular septal defect was imaged at the top of the IVS.
      The aorta was dextrally located and overriding both ventricles. The diagnosis was
      confirmed as tetralogy of fallot on postmortem examination.

PMID- 14960817
TI  - Intracranial granular cell tumor in a dog.
AB  - A 12-year-old female miniature poodle showed a 3-month history of neurological
      signs. Magnetic resonance imaging disclosed a high intensity tumor mass in the
      right cerebral hemisphere with compression of the lateral ventricle. At necropsy,
      a 2 x 3 cm white, friable mass was found in the right ventral pyriform lobe.
      Microscopically, the tumor cells were large, polygonal to round cells supported
      by a sparse fibrovascular stroma. The tumor cells typically possessed finely
      granular, pale eosinophilic cytoplasm with strongly positive periodic acid-Schiff
      (PAS) reaction. The tumor cells were immunopositive for vimentin, NSE and S-100.
      Ultrastructurally, the tumor cells showed large amounts of granules in the
      cytoplasm, and absence of basement membrane. Based on the above-mentioned
      findings, the intracranial granular cell tumor was diagnosed.

PMID- 14960818
TI  - Production and characterization of monoclonal antibodies against formalin
      inactivated Nipah virus isolated from the lungs of a pig.
AB  - Eight clones of monoclonal antibodies (Mabs) to Nipah virus (NV) were produced
      against formalin-inactivated NV antigens. They reacted positive by indirect
      immunofluorescent antibody test, and one of them also demonstrated virus
      neutralizing activity. They were classified into six different types based on
      their biological properties. These Mabs will be useful for immunodiagnosis of NV
      infections in animals and further research studies involving the genomes and
      proteins of NV.

PMID- 14960819
TI  - Fatty acid profiles in relation to triglyceride level in the liver of dairy cows.
AB  - To elucidate possible relationships between triglyceride (TG) levels and fatty
      acid composition in bovine liver, hepatic TG and seven individual fatty acids
      were measured in 23 Holstein dairy cows, of them 6 are healthy. Liver TG level
      was greater than 3 % in 12 cows which were ruled fatty liver. Palmitic and oleic
      acid proportions were significantly higher in fatty liver cows than in the
      healthy cows, while stearic acid was lower in fatty liver cows. With increased
      liver TG, stearic acid proportions decreased dramatically. Results indicate that
      hepatic lipidosis markedly alters the proportions of the various fatty acids in
      the liver of dairy cows.

PMID- 14960820
TI  - Detection of feline coronavirus antibody, feline immunodeficiency virus antibody,
      and feline leukemia virus antigen in ascites from cats with effusive feline
      infectious peritonitis.
AB  - To investigate the usefulness of ascites as a material for viral tests in cats
      with effusive feline infectious peritonitis (FIP), we attempted to detect anti
      feline coronavirus antibody, anti-feline immunodeficiency virus antibody, and
      feline leukemia virus antigen in ascites from 88 cats clinically suspected with
      effusive FIP. In each of these three viral tests, all cats positive for serum
      antibody/antigen were also positive for ascitic antibody/antigen, while cats
      negative for serum antibody/antigen were also negative for ascitic
      antibody/antigen. This finding indicates that ascites is useful for these viral
      tests.

PMID- 14960821
TI  - Cerebellopontine angle meningioma expanding into the sella turcica in a dog.
AB  - A 10-year-old, female poodle was presented with left paresis and vestibular
      signs, following left enophthalmus and atrophy of the cheek. Magnetic resonance
      imaging revealed a mass along the base of the brain and extending from the left
      cerebellopontine angle to the sella turcica. The mass showed isointensity on the
      T1-weighted image and T2-weighted image, and was enhanced by contrast medium (Gd
      DTPA). Although occipital craniotomy was carried out and the mass removed, the
      dog died without recovering from the anesthesia. The tumor was diagnosed
      pathologically as fibroblastic meningioma.

PMID- 14960822
TI  - Rhabdomyosarcoma in a ferret (Mustela putorius furo).
AB  - A 5-year-old spayed male ferret showed a subcutaneous mass in the right lateral
      thoracic wall. Microscopic examination revealed that the neoplasm had
      proliferated in the subcutis with infiltration into the surrounding tissues. A
      packed bundle of large polymorphic neoplastic cells, containing abundant
      eosinophilic cytoplasm and a round to ovoid, occasionally bizarre nucleus, were
      arranged interwoven. The neoplasm had metastasized to the right axillary lymph
      node. The neoplastic cells were intensively positive for vimentin, desmin and
      myoglobin. Skeletal muscle type creatine phosphokinase-positive granules were
      detected in the cytoplasm. Ultrastructurally, various amounts of disorganized
      myofibrils with focal density resembling the Z-band were shown in the cytoplasm
      of the neoplastic cells. The neoplasia was diagnosed as rhabdomyosarcoma.

PMID- 14960823
TI  - Allelic loss analysis of lymphomas induced in Fas-heterozygous deficient mice.
AB  - Mutations of Fas (CD95/Apo-1) gene have been reported in various malignancies and
      therefore the Fas gene has been considered to be a tumor suppressor gene. To
      examine an involvement of Fas gene as a tumor suppressor gene in radiation
      lymphomagenesis, we examined the loss of heterozygosity (LOH) in lymphomas from
      (MSM/Ms x MRL-MpJ/Fas (lpr)) F(1) and (BALB/cHeA x MRL-MpJ/Fas (lpr)) F(1) hybrid
      mice. Lymphoma development by X-irradiation was efficiently observed in both F(1)
      hybrids. Frequent LOH was found on chromosomes 12 and 4 in the tumors from both
      F(1) mice, but no allelic loss on chromosome 19 containing Fas locus was found,
      and no wild-type allele of the Fas gene was lost in 51 lymphomas. Therefore, the
      putative tumor-suppressor gene regions responsible for lymphomagenesis might not
      considerably differ due to the Fas gene status.

PMID- 14960824
TI  - Decreased apoptotic polymorphonuclear leukocyte rate in dogs with pyometra.
AB  - Polymorphonuclear neutrophil (PMN) apoptosis was examined in three dogs with
      pyometra by TUNEL assay in a 24-hr incubation period and compared with that in
      healthy control dogs (n=5). The incidence of apoptotic PMNs in dogs with pyometra
      was 26.4 +/- 5% and that in healthy dogs was 54.3 +/- 7%. The results indicated
      that apoptotic PMN rates in dogs with pyometra were significantly lower than
      those in control dogs (p<0.05), suggesting the prolongation of PMN survival.

PMID- 14960825
TI  - Occupational exposure associated with reproductive dysfunction.
AB  - Evidence suggestive of harmful effects of occupational exposure on the
      reproductive system and related outcomes has gradually accumulated in recent
      decades, and is further compounded by persistent environmental endocrine
      disruptive chemicals. These chemicals have been found to interfere with the
      function of the endocrine system, which is responsible for growth, sexual
      development and many other essential physiological functions. A number of
      occupations are being reported to be associated with reproductive dysfunction in
      males as well as in females. Generally, occupations involving the manufacture/or
      application of some of the persistent chemicals that are not easily degradable as
      well as bio-accumulative chemicals, occupations involving intensive exposure to
      heat and radiation, occupations involving the use of toxic solvents as well as
      toxic fumes are reported to be associated with reproductive dysfunction.
      Occupational exposure of males to various persistent chemicals have been reported
      to have male mediated adverse reproductive outcomes in the form of abortion,
      reduction in fertility etc. with inconclusive or limited evidence. Nevertheless,
      there is a need for more well designed studies in order to implicate any
      individual chemical having such effects as in most occupations workers are
      exposed to raw, intermediate and finished products and there are also several
      confounding factors associated with lifestyles responsible for reproductive
      dysfunction. There is an urgent need to look at indiscriminate use of persistent
      chemicals especially pesticides and persistent organic pollutants (POP's) as
      these chemicals enter the food chain also and could be potential for exposure
      during the critical period of development. It is also necessary to impart
      information, and to educate about the safe use of these chemicals, as a very
      sensitive reproduction issue is involved with exposure to these chemicals.
      Occupational exposures often are higher than environmental exposures, so that
      epidemiological studies should be conducted on these chemicals, on a priority
      basis, which are reported to have adverse effects on reproduction in the
      experimental system.

PMID- 14960826
TI  - Application of DNA microarrays in occupational health research.
AB  - The profiling of gene expression patterns with DNA microarrays is recently being
      widely used not only in basic molecular biological studies but also in the
      practical fields. In clinical application, for example, this technique is
      expected to be quite useful in making a correct diagnosis. In the pharmacological
      area, the microarray analysis can be applied to drug discovery and individualized
      drug treatment. Although not so popular as these examples, DNA microarrays could
      also be a powerful tool in studies relevant to occupational health. This review
      will describe the outline of gene expression profiling with DNA microarrays and
      prospects in occupational health research.

PMID- 14960827
TI  - Prevalence of musculoskeletal disorder among workers in Taiwan: a nationwide
      study.
AB  - Musculoskeletal disorder (MSD) is a common problem among workers. In spite of the
      numerous reports on MSD in various specific groups of workers, few data on the
      prevalence in the general working population are available except for back pain.
      We analyzed the information collected through a nationwide survey in Taiwan in
      1994 to estimate the prevalence of MSD by age, gender, and education level and
      identify high-risk industries. In the survey, a standard questionnaire was
      distributed to a representative sample of 22,475 non-self-employed workers in
      Taiwan. National estimates were obtained by applying a weight to each
      participant. Among the sampled workers, 18,942 (84.3%) participated, and 37.0%
      (standard error=0.4%) had MSD. Female workers had a significantly higher overall
      prevalence than male workers (39.5% vs. 35.2%, p<0.05). Education and age also
      had significant associations with MSD (p<0.001 in both genders). "Lower back and
      waist" were the most frequently affected body parts (18.3% among males and 19.7%
      among females), but the prevalence of MSDs of the neck, shoulders, hands and
      wrists were also above 10%. The top ten high-risk major industries for MSD of
      various body parts for each gender were identified, and some industries,
      including "Basic Metal Industries" and "Buildings Construction," were among the
      top ten for multiple body parts. Our study showed that MSDs of body parts other
      than the back are also prevalent, especially in the neck, shoulders, hands and
      wrists. We also identified high-risk industries for further research and
      intervention.

PMID- 14960828
TI  - Lung cancer risk in male dentists: a retrospective cohort study in Japan, 1964
      1997.
AB  - It is reported that dentists are exposed to heavy metals in their clinics. To
      assess the risk of developing lung cancer among male Japanese dentists, we
      conducted a retrospective cohort study of 3,314 members of Osaka Dental
      Association (Osakafu-Shikaishikai). During 1964-1997, 39 were diagnosed with lung
      cancer, which figure was obtained from the file of the Osaka Cancer Registry. The
      observed number of lung cancers was compared with the expected number calculated
      by multiplying the number of person-years at risk by the corresponding age- and
      calendar time-specific incidence rate from the Osaka Cancer Registry data. The
      male dentists had no significantly different risk than general
      population.(O/E=1.01, 95%CI=0.72-1.39). Contrary to expectation, these findings
      indicate that Japanese dentists had almost the same overall risk of developing
      lung cancer as the general population.

PMID- 14960829
TI  - External validation of psychological job demands in a bus driver sample.
AB  - Psychosocial risk factors have been considered as characteristics of the work
      environment rather than an individual issue, but their presence in the workplace
      is usually measured by self-reported questionnaires, based on worker attitudes.
      The objective of the study was to compare a self-reported measure of
      psychological job demands in a bus driver sample with selected indicators of bus
      company activity, as external 'objective' indicators, in order to assess its
      external validity. The final sample included 713 drivers in 41 routes. Self
      reported measures of psychosocial work risk factors were obtained by the Job
      Content Questionnaire (JCQ). Four external indicators were available for each
      route: passengers, break times, bus incidents, and regulating actions. Spearman's
      correlation coefficient was estimated to assess the validity. Correlation
      coefficients showed that self-reported psychological demands were statistically
      significant correlated (p<0.05) with two external indicators: bus incidents
      (rho=0.397), and regulating actions (rho=0.475). Self-reported psychosocial risk
      factors have been compared with independent external indicators of the
      psychosocial work environment, trying to avoid any subject's perception.
      According to our results, psychological demands measured by the JCQ seem to
      reflect the actual psychosocial work environment. Other studies are necessary to
      confirm these results and to assess job control and job social support. This
      would be another step in improving our knowledge of the quality of measurement of
      psychosocial risk factors.

PMID- 14960830
TI  - Perfluorooctanoate and perfluorooctane sulfonate concentrations in surface water
      in Japan.
AB  - Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are synthetic
      surfactants used in Japan. An epidemiological study of workers exposed to PFOA
      revealed a significant increase in prostate cancer mortality. A cross-sectional
      study of PFOA-exposed workers showed that PFOA perturbs sex hormone homeostasis.
      We analyzed their concentrations in surface water samples collected from all over
      Japan by LC/MS with a solid phase extraction method. The lowest limits of
      detection (LOD) (ng/L) were 0.06 for PFOA and 0.04 for PFOS. The lowest limits of
      quantification (LOQ) (ng/L) were 0.1 for both analytes. The levels [geometric
      mean (GM); geometric standard deviation (GS)] (ng/L) of PFOA and PFOS in the
      surface waters were GM (GS): 0.97 (3.06) and 1.19 (2.44) for Hokkaido-Tohoku
      (n=16); 2.84(3.56) and 3.69 (3.93) for Kanto (n=14); 2.50 (2.23) and 1.07 (2.36)
      for Chubu (n=17); 21.5 (2.28) and 5.73 (3.61) for Kinki (n=8); 1.51 (2.28) and
      1.00 (3.42) for Chugoku (n=9); 1.93 (2.40) and 0.89 (3.09) for Kyushu-Shikoku
      (n=15). The GM of PFOA in Kinki was significantly higher than in other areas
      (ANOVA p<0.01). Systematic searches of Yodo and Kanzaki Rivers revealed two
      highly contaminated sites, a public-water-disposal site for PFOA and an airport
      for PFOS. The former was estimated to release 18 kg of PFOA/d. PFOA in drinking
      water in Osaka city [40 (1.07) ng/L] was significantly higher than in other
      areas. The present study confirms that recognizable amounts of PFOA are released
      in the Osaka area and that people are exposed to PFOA through drinking water
      ingestion.

PMID- 14960831
TI  - A study of the effects of active listening on listening attitudes of middle
      managers.
AB  - The present study was conducted to clarify the direct effects of active listening
      (AL) training given to middle managers in a local government. Altogether, 345
      middle managers participated in 13 AL training sessions over two years. We
      developed the Inventive Experiential Learning (IEL) method, and used it as the
      central training method in this study. To investigate how well the participants
      learned AL, we asked the middle managers to answer a shorter version of the
      Active Listening Attitude Scale (ALAS) consisting of two subscales-i.e.
      "Listening Attitude" and "Listening Skill"-before training, one month after and
      three months after training. Altogether, 284 middle managers answered the
      questionnaire three times. The scores of each subscale were analyzed by repeated
      measurement analysis of variance. The participants were divided into three groups
      using the percentile values of the original sample of ALAS, i.e. low-score group
      (-24%), medium-score group (25-75%) and high-score group (76%-), and the
      proportionate changes were examined. The results showed both the "Listening
      Attitude" and "Listening Skill" subscales increased significantly after training.
      Analysis of the percentiles showed that the proportion of the low-score group
      decreased and that of the high-score group increased in both subscales, from one
      to three months after training. These changes are considered to indicate that the
      participants have learned AL although they attended AL training for only one day.

PMID- 14960832
TI  - A 3-year follow-up study of anti-Legionella antibodies in users of Japanese 24
      hour hot water baths.
AB  - Although it has been found that legionellae can exist in a 24-h hot water bath
      (24HHWB), which has been used recently in Japan, whether longer use of the 24HHWB
      causes legionellosis is unclear. The present longitudinal study was conducted in
      2000 to investigate the 3-yr change in antibody titers in association with the
      continuous use, non-use, or canceling the use of the 24HHWB, and possible factors
      relating to the antibody changes. Ninety-two subjects (85 males and 7 females),
      who had had their anti-Legionella pneumophila (Lp) serum antibody titers measured
      in our initial study in 1997 and consented to blood sampling 3 yr later, were
      selected as subjects. There were no clinical cases who had experienced
      Legionnaires' disease or Pontiac fever during the 3 yr. The continuous users
      showed no significant changes in antibody titers within 3 yr, whereas the
      continuous non-users had a significant increase in antibody titers against the Lp
      serogroup (SG) 5 and 6. Eleven ex-users of the 24HHWB showed a significant
      decrease in antibody titers against Lp SG 6. The changes in the 24HHWB use, job
      sector, stress coping strategies, and alcohol-drinking habit were associated with
      the changes in antibody titers against Lp SG 1, 5 or 6. The anti-Lp antibodies
      were considered to be IgM dominant. In conclusion, this study indicates that
      24HHWB use by healthy subjects does not tend to result in a higher onset risk of
      legionellosis, even if it is continuously used for 3 yr, although 24HHWB use is
      likely to induce production of antibodies against legionellae.

PMID- 14960833
TI  - Relationship between effort-reward imbalance, low social support and depressive
      state among Japanese male workers.

PMID- 14960834
TI  - Chromatography-mass spectrophotometric techniques for air pollutants: a
      commentary.

PMID- 14960835
TI  - The role of voluntary consumer organisations in genetic services in the United
      kingdom.
AB  - This article describes the role of the Genetic Interest Group (GIG), a UK
      alliance of charities and voluntary groups for families affected by specific
      genetic disorders, as an advocate for the needs of patients and their families
      and as an agent of change in the development of genetic services in the UK. GIG
      now interacts with a wide range of audiences - lay groups, the professional
      community, policy makers, government and the media - in a variety of different
      ways, so that the perspective of the 'end user' is reflected in decisions about
      the application of the new genetics in the field of human health.

PMID- 14960836
TI  - Common language for measures of occurrence of congenital anomalies and genetic
      diseases: incidence or birth prevalence.
AB  - Scientists involved in the epidemiology of congenital anomalies (including
      genetic diseases) use many terms to describe the occurrence of these disorders
      amongst births, such as 'incidence', 'prevalence' and 'rate'. Yet it is clear
      that often 'prevalence' is the only meaningful measure for the proportion of
      births affected with a certain congenital or genetic disorder. 'Incidence' and
      'rate' are usually inappropriate, as the assessment of the frequency of a
      disorder is not a matter of following up a cohort of healthy individuals until
      they fall ill.

PMID- 14960837
TI  - French physicians' knowledge about hereditary breast/ovarian cancer: the need for
      continuing vocational training in genetics.
AB  - OBJECTIVES: The aim of this study was to determine what medical specialists knew
      about recent findings in the genetics of breast/ovarian cancer, according to
      their speciality and the methods they used to keep themselves up to date.
      METHODS: A national random sample of 1,169 surgeons and gynaeco-obstetricians was
      surveyed using a mailed questionnaire, to which 700 of those contacted responded
      (60%). RESULTS: Two years after it had been identified, BRCA1 was known by only
      54% of the practitioners, whereas BRCA2 was known by 49.1% 1 year after it was
      first identified. The lifetime breast cancer risk of women in the general
      population was estimated by 37.6% of the participants to be between 6 and 10%,
      and 35.7% rated the penetrance of a breast cancer mutated gene at between 70 and
      90%. After multivariate adjustment, the overall score for knowledge of hereditary
      breast/ovarian cancer was mainly determined as follows: by the speciality (p <
      0.001), since the gynaeco-obstetricians scored the highest and the general
      surgeons the lowest; by the size of practice (p < 0.001), since a larger practice
      was associated with a higher score, and by whether or not the participants were
      accustomed to reading the international literature (p < 0.01). CONCLUSIONS: These
      results show the need for physicians who are not geneticists to acquire further
      knowledge about cancer genetics. We discuss the role of international reviews in
      communicating the latest knowledge available in genetics to specialists working
      in other medical fields.

PMID- 14960838
TI  - Prevalence of pedigrees suggestive of hereditary nonpolyposis colorectal cancer
      among a community sample of women eligible for screening mammography.
AB  - OBJECTIVE: To determine from a large cohort of women eligible for screening
      mammography, the number who would meet criteria for genetic testing for
      hereditary nonpolyposis colorectal cancer (HNPCC). METHODS: Detailed personal and
      family cancer histories, obtained from 6,682 women aged 50-80 years randomly
      selected from communities in Washington State, were matched to the Amsterdam
      criteria, Bethesda guidelines, and Japanese criteria for HNPCC. RESULTS: One
      (0.015%) respondent met the Amsterdam criteria, 2 (0.035%) met the Japanese
      criteria and 5 (0.075%) met the Bethesda guidelines. CONCLUSION: Using the time
      of presentation for initial mammography as an opportunity to screen for HNPCC
      would detect very few families at high risk for this condition.

PMID- 14960839
TI  - The epidemiology of myotonic dystrophy in Northern Ireland.
AB  - Multiple sources of ascertainment were used to identify families with myotonic
      dystrophy in Northern Ireland. A total of 59 families with 188 living affected
      members were identified. The prevalence rate was 119.5 x 10(-6) in a total
      population of 1.5 million, a rate similar to neighbouring communities.
      Information about the natural history of the disease in these families enabled
      analysis of age of onset, fertility, fitness and age at death.

PMID- 14960840
TI  - Etiological characterization of 512 severely mentally retarded institutionalized
      patients in havana.
AB  - OBJECTIVE: To investigate etiological factors in severe mental retardation (SMR).
      METHODS: An etiological study is presented of 512 SMR patients in five
      specialized institutions in Havana. RESULTS: Prenatal, perinatal and postnatal
      causes were apparent in 58.0, 24.8 and 11.1% of the patients, respectively;
      infantile psychosis was determined in only 0.4%. The remaining 5.6% were
      classified as having SMR of undeterminable origin, i.e. patients with apparently
      normal pre-, peri- and postnatal histories who had neither dysmorphism nor
      affected first-degree relatives, and had a normal karyotype and metabolic screen.
      Among prenatal causes, genetic factors were the most frequent (82.8%), while
      environmental factors were apparent in only 5.3% of these cases. Of the cases
      with prenatal genetic etiology, chromosomal aberrations were present in 86.5%
      (Down syndrome 96.2% and 3.7% other chromosomal aberrations), monogenic disorders
      in 11.3% [neurocutaneous diseases (32.1%) and fragile X syndrome (25%) were the
      most frequent], and multifactorial disorders in 2.0%. Thirty-five patients
      (11.7%) presented multiple congenital anomalies of 'prenatal unknown' causes. The
      latter group may include unidentifiable chromosomal aberrations, uniparental
      disomy, de novo mutations and multifactorial or teratogenic factors. CONCLUSION:
      Accurate determination of the etiology of SMR is important not only for genetic
      counseling purposes, but also in identifying prenatal events which make infants
      more vulnerable to perinatal risk factors.

PMID- 14960841
TI  - Living with Machado-Joseph disease in a small rural community of the Tagus
      valley.
AB  - OBJECTIVES: In the context of our national program of predictive testing for
      Machado-Joseph disease (MJD), we have studied in a small rural community (1)
      discourses about the illness by individuals at risk and patients, and (2) how
      individuals at risk and patients plan to cope with the familial illness. METHODS:
      We used qualitative methods, beginning with a group interview of individuals at
      risk, and followed by in-depth interviews (about 1 hour long) of at-risk and
      affected individuals, in their homes. The latter interviews were subjected to a
      content analysis. RESULTS: The coexistence of two contradictory discourses about
      MJD (a scientific and a folk one) was found consistently among all individuals.
      The main metaphor was that of the 'drunkard'. Knowledge about a precise diagnosis
      of their disease produced relief and hope, because it provided evidence that
      affected individuals were not drunkards. CONCLUSIONS: The understanding of
      beliefs about the disease and its social representation is essential in planning
      effective genetic and psychological counseling.

PMID- 14960842
TI  - Services for the prevention and management of genetic disorders and birth defects
      in developing countries.

PMID- 14960874
TI  - 40 years later: the health related quality of life of women affected by
      thalidomide.
AB  - OBJECTIVES: 40 years ago, the sudden increase of births of babies with a range of
      severe deformities shocked the world. It was caused by the tranquilizer
      thalidomide. Women who took the drug in the first trimester of pregnancy gave
      birth to children with a wide but distinctive range of malformations. Thalidomide
      claimed more than 10,000 victims worldwide. Those who survived are now reaching
      middle age. Especially women affected by thalidomide may be at special
      disadvantage because of combined discrimination based on gender and disability.
      So far, no study has been published that has investigated their quality of life
      in health and in health care. METHODS: A questionnaire using the WHO QOL-BREF
      instrument for measuring health-related quality of life was distributed among 166
      females impaired by thalidomide. A randomized control group matched by age, sex
      and area of residence filled out a corresponding questionnaire. RESULTS: Women
      impaired by thalidomide reported significantly lower quality of life in health
      and health care as compared to their control group. Over a third reported
      steadily deteriorating conditions, and a statistically significant higher
      proportion as compared to the controls has already retired from the workforce.
      They were significantly less frequently married, had fewer children, had less
      household incomes and were less mobile. However, women impaired by thalidomide
      are more likely to be satisfied with their safety in daily life, with their
      physical environment, with their living conditions and with the support they get
      from their friends. CONCLUSIONS: Although there is increasing clinical research
      on how to use thalidomide as a drug in new therapies, the specific health needs
      of women impaired by thalidomide are at risk of being neglected.

PMID- 14960875
TI  - Screening for C283Y gamma-sarcoglycan mutation in a high-risk group of Bulgarian
      Gypsies: evidence for a geographical localization and a non-random distribution
      among Gypsy subgroups.
AB  - Limb-girdle muscular dystrophy type 2C (LGMD2C) is an autosomal recessive
      disorder caused by mutations in the gamma-sarcoglycan gene. A 'private' Gypsy
      C283Y mutation was detected in this gene. Recently, a number of LGMD2C-affected
      families belonging to a Xoroxane Gypsy group have been detected in eastern
      Bulgaria and all of these cases were due to the same mutation. We have screened
      300 unrelated individuals of reproductive age from this high-risk Xoroxane Gypsy
      group, settled in Sliven. The genetic test by PCR-SSCP analysis for the C283Y
      mutation revealed a carrier frequency of 7.7%. The screened sample was ethnically
      not homogeneous. It was divided in ethnonym groups on the basis of social and
      economic status, language characteristics and trades. We found that the C283Y was
      not randomly distributed among the Gypsy subgroups. The disease seemed to be
      limited to the Xoroxane Gypsy group and geographically localized in eastern
      Bulgaria.

PMID- 14960876
TI  - Knowledge and attitudes of Hispanic women and their health care providers about
      breast cancer risk factors and screening.
AB  - OBJECTIVES: The purpose of our study was to develop and evaluate an educational
      program for health care providers and patients on the topics of general breast
      cancer risk factors, breast cancer genetics, and breast cancer screening
      recommendations. The program was designed with specific emphasis on addressing
      the needs of medically underserved Hispanic women in Southern Texas. We also
      identified and compared perceptions of potential barriers to breast cancer
      screening. METHODS: The educational program was piloted with patient and health
      care provider focus groups. After incorporating modifications suggested by the
      focus groups, 103 patients and 94 health care providers (HCPs) from community
      health clinics in Harris County, Tex., were recruited to participate in the
      study. Changes in knowledge were measured through the use of pre- and postseminar
      questionnaires. RESULTS: The program identified various misconceptions about
      breast cancer in representative groups of patients and HCPs. Comparison of pre-
      and post-test scores indicated that both groups made significant gains in
      knowledge about breast cancer and breast cancer screening. Participant
      evaluations indicated that the seminar was informative and interesting. Both
      patients and HCPs agreed that the cost of breast cancer screening and the lack of
      sufficient bilingual HCPs were 'major' barriers to obtaining breast cancer
      screening, but had differing opinions regarding other potential barriers.
      CONCLUSIONS: We have developed an effective method of education about breast
      cancer risk factors and screening for two groups: Hispanic women of lower
      educational and socioeconomic levels, and the HCPs who serve them. Based on the
      successful reception of our program, we propose extending it to other areas of
      Texas with demographics similar to those of the study population.

PMID- 14960877
TI  - Familial aggregation of early-onset myocardial infarction.
AB  - Although ischemic heart disease tends to cluster in families, previous studies
      have reported a modest (2-fold increased risk) to strong (10-fold increased risk)
      contribution of family history to the explanation of disease occurrence. The
      authors assessed the familial aggregation of early-onset myocardial infarction in
      11,307 adults aged <65 years who participated in the Third National Health and
      Nutrition Examination Survey. Logistic regression was used to obtain odds ratios
      (ORs) and 95% confidence intervals (CIs). A parental history was more common in
      those with (n = 237) than in those without (n = 11,070) a myocardial infarction
      (19.8 vs. 7.9%, p < or = 0.01). Adults with a parental history were also more
      likely to have multiple risk factors for cardiovascular disease (OR for four or
      five risk factors compared with none: 2.9, 95% CI: 1.4, 6.3). After multivariate
      adjustment, the likelihood of myocardial infarction was more than three times
      greater among adults with a parental history than among those without (95% CI:
      1.7, 6.7). A maternal history of myocardial infarction was strongly associated
      (OR = 6.1, 95% CI: 2.1, 17.4) with an increased likelihood of myocardial
      infarction, and a paternal history was associated with a 3-fold (95% CI: 1.5,
      6.3) increased likelihood of myocardial infarction after adjustment for
      cardiovascular disease risk factors. These results suggest a familial aggregation
      of early-onset myocardial infarction and show that family history is strongly
      associated with cardiovascular disease risk factors.

PMID- 14960878
TI  - Perceptions of Mexican American clients receiving genetic services in South
      Texas.
AB  - OBJECTIVES: The objectives of this study were to assess the perceptions among
      medically indigent Mexican American clients in South Texas receiving genetic
      services, and the effects of these perceptions on the utilization of genetic
      services. METHODS: Using a qualitative ethnographic approach, 16 caretakers of
      children with genetic conditions and 7 prenatal clients were interviewed.
      Interview data were analyzed using the NUD*IST 4 computer program. RESULTS:
      Clients reported challenges with understanding and utilizing genetic services due
      to language and communication barriers, poverty, cultural differences, and system
      issues. CONCLUSION: Client perceptions of genetic services were influenced by
      experiences with other biomedical providers and traditional healers, and by
      anxieties precipitated by unfamiliar concepts and approaches to medical care.
      Recommendations are made to improve provision of genetic services.

PMID- 14960879
TI  - Risk factors for neonatal mortality in low-income population subgroups in
      Karachi, Pakistan.
AB  - This paper assesses the risk factors for neonatal mortality (0-28 days of life)
      for full-term singleton live births. The study sample comprised 1,011 ever
      married women who were residents of four multi-ethnic, multi-religious low-income
      areas of Karachi, Pakistan during 1995. The analysis sample was restricted to
      4,488 live births to 912 women. Results showed that 4.8% (n = 217) of all births
      ended in death in the neonatal period, and 76% (n = 164) of these neonatal deaths
      occurred in the first week of life. While neonatal mortality rates had declined
      appreciably over time, a large proportion of neonatal deaths were clustered in a
      small group of women. The univariate analysis showed a statistically significant
      association between a number of maternal-level parameters (e.g., mother's age at
      birth, level of formal education, employment status, religious affiliation, and
      consanguinity) and child-level parameters (e.g., birth order, birth interval,
      survival status of the preceding child, sex of the neonate, year of death). At
      the multivariate level, consanguinity, birth order and year of death were found
      to be statistically significant risk factors for neonatal mortality analyses
      despite adjustment for death clustering. The study highlights the importance of
      inbreeding as a determinant of early offspring death, and points to the need for
      better understanding of why deaths are clustered in certain families. Given the
      widespread practice of close cousin marriages in Pakistan across all socio
      economic groups, there is a need to validate the findings in less economically
      disadvantaged population subgroups within the country.

PMID- 14960880
TI  - A survey on inborn errors of metabolism in 323 neonates from the state of Rio de
      Janeiro, Brazil.
AB  - Inborn errors of metabolism (IEM) are a relevant cause of morbidity and death
      among children, and neonates in particular. However, little is known about the
      prevalence of these disorders in Brazilian newborns. Our laboratory of IEM
      (LABEIM) at the Department of Biochemistry, Institute of Chemistry, Federal
      University of Rio de Janeiro (UFRJ), has been working on the diagnosis of IEM
      since 1988. Out of 3,300 patients (90% children), screened and evaluated from
      1989 to 2,000 because of a high clinical suspicion of having an IEM, 323 (9.8%)
      were neonates. Patients came from different regions of the state of Rio de
      Janeiro, in which lives approximately 8.5% of the total Brazilian population.
      Chemical tests, various chromatographic techniques and enzyme assays were
      performed in urine, plasma and in some cases, cerebrospinal fluid (CSF). This
      study describes our laboratory and the experience with the 323 investigated
      neonates, among which 28 cases (8.7%) of IEM were identified and 18 (5.6%),
      strongly suspected. All these cases were related mainly to the metabolism of
      amino acids, organic acids, lysosomal enzymes and carbohydrates. Furthermore,
      data on population, community and health services are presented.

PMID- 14960882
TI  - Community genetics in developing countries.

PMID- 14960881
TI  - Pilot study of early diagnosis of hereditary haemochromatosis through systematic
      case finding in primary care.
AB  - OBJECTIVES: To test the feasibility of adopting and evaluating a systematic case
      finding approach to the early diagnosis of hereditary haemochromatosis (HHC) in
      primary care, and to estimate the prevalence of presenting conditions for which
      HHC testing could be offered. METHODS: Systematic identification of, and
      genotyping for, C282Y and H63D mutations in patients presenting in primary care
      with possible symptoms of HHC during a 4-week period to 1 of 14 doctors in
      Oxfordshire. RESULTS: From a total of 4,022 consultations, 169 (4.2%; 95% CI: 3.6
      4.8) adult patients had possible symptoms of HHC. Of these, 88 (2.2%; 95% CI: 1.7
      2.6) were aged 25-70 and were offered genotyping for HHC, of whom 60 agreed to be
      tested. There were no C282Y homozygotes (0%; 95% CI: 0-6.0), no C282Y/H63D
      compound heterozygotes (0%; 95% CI: 0-6.0), 2 H63D homozygotes with normal iron
      indices (3.3%%; 95% CI: 0.4-11.5) and 3 C282Y heterozygotes (5.0%; 95% CI: 1.0
      13.9). CONCLUSIONS: This study raises doubts about a case-finding approach to
      early diagnosis of HHC in primary care. The non-specific nature and high
      prevalence of possible symptoms of HHC in primary care mean that many patients
      would require testing to identify a single case. Whether this offers a more cost
      effective alternative to population screening requires further study.

PMID- 14960883
TI  - Understanding inherited disease through human migrations: a south-west Asian
      perspective.
AB  - Mitochondrial DNA (mtDNA) and the Y chromosome are inherited in a haploid manner
      and have been used extensively to reconstruct human lineages. mtDNA and the
      majority of the Y chromosome lack recombination and show high rates of apparently
      neutral mutation. Here, we demonstrate how detailed analysis of these uniparental
      inherited markers can reveal general and more subtle population movements within
      south-west Asia. These include a major migration of modern humans from East
      Africa to western and southern Asia around 60,000 YBP, migrations of populations
      from the Fertile Crescent in south-western Iran to India approximately 8,000 YBP,
      and migrations of Indo-European speakers from Central and West Asia to India
      approximately 5,000 YBP. We highlight how the understanding of these, and other
      population movements, can be useful in tracing the dispersal of disease-causing
      mutant alleles, and how these data could be applied to predicting the segregation
      of mutant alleles within populations.

PMID- 14960884
TI  - Castes, migration, immunogenetics and infectious diseases in south India.
AB  - It has been said that the grandest genetic experiment of nature has been
      conducted in south India in the name of the caste system. One can expect the
      frequency of an infectious disease to be equal to the product of the frequencies
      of various indicated loci/alleles, whether physiological, hormonal or
      immunological, in an endemic area. The sympatrically isolated caste and sub-caste
      populations of southern India, with differing origins, migration patterns and
      breeding habits, differ significantly in their HLA and other immune repertoire
      and are ideal models to study and test this hypothesis. The prevalence of a
      number of major infectious diseases, including TB and leprosy, are reviewed in
      different communities in the light of their genetic history.

PMID- 14960885
TI  - Genetic diversity in the human major histocompatibility complex: lessons for
      vaccination approaches to HIV infection.
AB  - The major histocompatibility complex (MHC) harbours genes that have a primary
      function of regulating immune responsiveness. Our data on the distribution
      patterns of molecular subtypes of HLA class I and II extended haplotypes in India
      suggest that: (1) Asian Indians have extreme diversity in the MHC region, with
      several novel and unique alleles and disease-associated MHC haplotypes (e.g. the
      autoimmune-favouring A26-B8-DR3 haplotype); (2) there have been selective
      environmental and microbial pressures in India that directed either the
      generation of novel alleles through founder effect or the expansion of other
      alleles due to geophysical or socio-economic barriers, and (3) Asian Indians have
      a unique repertoire of peptide-presenting molecules to deal with pathogen-derived
      autoreactive antigens. This level of polymorphism concentrated within the MHC
      presents a formidable obstacle to the development of peptide-based vaccines, e.g.
      for AIDS. Further, studies conducted by us and others have provided a genetic
      basis for the possible predisposition and fast progression of HIV infections in
      the Indian population. Since there is selective predominance of different HLA
      alleles and haplotypes in different populations, a dedicated global screening
      effort is required to develop MHC-based vaccines against infectious diseases.

PMID- 14960886
TI  - FMR1 haplotype analysis among Indian communities.
AB  - OBJECTIVE: To analyse fragile X mental retardation 1 haplotypes among non-fragile
      X males from different Indian caste-based communities in order to enable inter
      community comparisons to be made and permit wider comparisons with other ethnic
      groups. SUBJECTS AND METHODS: Males (n = 124) from four major Hindu castes
      (Brahmins, Kshatriyas, Vaishyas and Shudras) and the Indian Muslim community were
      typed using three STR markers, DXS548, FRAXAC1, and FRAXAC2. RESULTS AND
      CONCLUSION: A wide range of haplotypes were observed, with 7-3-4+ being modal in
      Brahmins, Kshatriyas, and Vaishyas. This finding is in keeping with data from
      other Caucasian populations of European and North American origin. The report is
      the first of its kind, providing a normative background for meaningful haplotype
      comparisons between different Indian communities and with the fragile X
      individuals.

PMID- 14960887
TI  - Common psychiatric diseases and human genetic variation.
AB  - OBJECTIVE: A better understanding of human genetic variation is important in
      assessing disease epidemiology and phenotypic variation, and may be critical in
      evaluating genetic aspects of common genetic diseases, such as schizophrenia,
      bipolar disease and Parkinson's. These diseases are particularly difficult to
      investigate as there are few peripheral markers, and although a genetic aetiology
      has long been suspected, robust findings have been hard to establish. METHODS:
      Variations in alleles at 13 tri-nucleotide gene loci expressed in the brain and
      implicated in several neurodegenerative diseases, as well as certain other loci,
      were examined in the Indian population for comparison with other major ethnic
      groups. RESULTS AND CONCLUSION: In the Indian population, the distribution of
      alleles at the Machado-Joseph disease locus was similar to the Western European
      pattern of distribution. Analysis of haplotypes at the locus for Huntington's
      disease suggested multiple origins, and possible effects of population admixture
      because of the recent history of the country. At other alleles of
      neuropsychiatric interest (dopamine receptor, serotonin receptor, serotonin
      transporter, alcohol dehydrogenase), allele frequencies in the Indian population
      differed from other populations. Interspecies comparison suggests a gradual
      expansion in repeat size, with the exception of the CLOCK gene, which displays a
      contraction of CAG repeat numbers. World-wide differences in disease phenotypes
      need to be explored, and an appreciation of their genetic basis may provide a
      window of opportunity for improving our knowledge of the underlying genetic
      mechanisms.

PMID- 14960888
TI  - The influence of consanguineous marriage on infant and child mortality among
      Palestinians in the West Bank and Gaza, Jordan, Lebanon and Syria.
AB  - OBJECTIVES: The purpose of this paper is to explore the characteristics of
      mortality differences associated with consanguineous marriage among Palestinians
      in the Middle East. METHODS: The data came from five surveys of Palestinians
      living in the West Bank and Gaza, Syria, Jordan and Lebanon, conducted during the
      period 1995-2000. Infant and child mortality was estimated for the offspring of
      consanguineous and non-consanguineous parents using the synthetic cohort method.
      RESULTS: The data showed an increase in infant mortality of 15.0 additional
      deaths per 1,000 births among the offspring of first cousins, and a corresponding
      increase of 6.1 deaths per 1,000 for the progeny of parents from the same
      patrilineal clan. CONCLUSION: In populations where marriage within kin groups is
      common, both first cousin marriage and intra-group marriage carries an added risk
      of infant and child mortality.

PMID- 14960889
TI  - Consanguinity and ocular genetic diseases in South India: analysis of a five-year
      study.
AB  - OBJECTIVE: Consanguineous marriage is a widely practised social custom in Asia
      and northern Africa. In south India, Dravidian Hindus have contracted
      consanguineous marriages for over 2,000 years. In the present study, the
      influence of consanguinity on the prevalence of visual disorders was examined in
      patients attending a specialist genetic eye clinic. SUBJECTS AND METHODS: A total
      of 2,335 patients attending Sankara Nethralaya, Chennai, India, were screened for
      genetic eye disorders over a five-year period. The patients were drawn from all
      parts of India and from neighbouring countries in south Asia. RESULTS AND
      DISCUSSION: Six hundred and seventy-three (28.8%) of the patients tested for
      ophthalmic genetic disorders reported a family history of consanguinity. The
      majority (n = 574) of these families were from south India. In the patient group
      as a whole, the most common form of consanguineous union was between first
      cousins (n = 367), followed by uncle/niece marriage (n = 177), equivalent to a
      mean coefficient of inbreeding alpha = 0.0202. Among the consanguineous families,
      430 of 673 (63.9%) had retinitis pigmentosa, 167 of these cases were autosomal
      recessive and 199 were isolated cases. The public in regions such as south India
      should be made aware of the merits and demerits of consanguineous marriages.

PMID- 14960890
TI  - Cerebral lipidoses in patients with progressive neurodegeneration: a study from
      south India.
AB  - OBJECTIVE: To study the prevalence and clinical profile of cerebral lipidoses in
      patients with progressive neurodegeneration. SUBJECTS AND METHODS: A total of 771
      patients clinically diagnosed with a progressive neurodegenerative disease were
      investigated for lipidoses. Specific enzyme assays in serum and leucocytes and
      other relevant investigations, including histopathology, neuroimaging and
      neurophysiological studies were conducted when indicated. RESULTS: Fifty-four
      cases of sphingolipidoses and 1 case of sialidosis type 1 were diagnosed. The
      sphingolipidoses consisted of 30 cases of metachromatic leukodystrophy, 13 cases
      of Tay-Sachs disease and its variants, 11 cases of Sandhoff disease, and 1 case
      each of Niemann-Pick disease and multiple sulphatase deficiency. The clinical
      features were similar to earlier reports. Parental consanguinity was present in
      63.6% of patients. CONCLUSIONS: In south India, where consanguineous marriages
      are strongly favoured, inherited diseases such as the cerebral lipidoses should
      be considered when evaluating a patient with progressive neurodegeneration. The
      establishment of specialised referral centres would provide a helpful approach to
      the prevention and management of these fatal disorders.

PMID- 14960891
TI  - The burden of genetic disorders in India and a framework for community control.
AB  - With a very large population and high birth rate, and consanguineous marriage
      favoured in many communities, there is a high prevalence of genetic disorders in
      India. An estimated 495,000 infants with congenital malformations, 390,000 with
      G6PD deficiency, 21,400 with Down syndrome, 9,000 with beta-thalassaemia, 5,200
      with sickle cell disease, and 9,760 with amino acid disorders are born each year.
      The prevalence of late-onset multi-factorial disorders (including coronary artery
      disease, hypertension and psychiatric disorders) is also large. Due to inadequate
      diagnostic, management and rehabilitation facilities, the burden of these
      disorders is greater than in Western countries. Although genetic diseases receive
      little attention from the health services, research funding by the government has
      been liberal. Community control of common disorders like thalassaemia, Down
      syndrome, neural tube defects, and muscular dystrophies deserves high priority,
      and genetic services should be integrated into the existing primary health care
      and medical services. Most genetic counselling would have to be provided through
      training physicians who staff the district and medical school hospitals. To
      ensure future progress, there is a need to establish additional departments of
      medical genetics in medical schools.

PMID- 14960892
TI  - Genetic disorders in haematological practice in India.
AB  - Haemoglobinopathies represent a significant national health burden in India. The
      distribution of specific disorders varies geographically and by community.
      Heterozygote frequencies of beta-thalassaemia range from 1 to 15%, resulting in
      an estimated 20 million carriers. HbS is mainly present in tribal and non-caste
      communities, with carrier prevalences of up to 40%. By comparison, alpha
      thalassaemia carriers are found in both the caste and tribal communities, and can
      reach a frequency of >90% in the latter case. Community control of
      haemoglobinopathies relies mainly on out-reach education programmes and genetic
      counselling, with antenatal diagnosis offered in specific major centres. Only
      partial data are available on the prevalence of haemophilia, but it has been
      estimated that there are some 50,000 affected individuals nationwide, with an
      additional 1,500 new cases born each year. RFLP-based techniques have been
      established to detect mutations in the factor VIII and IX genes, enabling the
      limited introduction of carrier detection and antenatal diagnosis.

PMID- 14960893
TI  - Intellectual disability and cerebral palsy in a UK community.
AB  - OBJECTIVE: The northern English city of Bradford has a population of 370,000. In
      recent years the Pakistani community has gradually expanded in number, and in
      2001 contributed 41.4% of births in the city. There is a very high level of
      consanguineous marriage in this community, and the main aim of this study was to
      assess the influence of community endogamy and consanguinity on major disabling
      childhood diseases. SUBJECTS AND METHODS: More than 300 children are referred to
      the Child Development Centre each year. Data on neurodegenerative disorders,
      microcephaly and cerebral palsy were collated and analysed by community of origin
      and mode of inheritance. RESULTS AND CONCLUSIONS: There was a striking variation
      in the prevalence of many disabling conditions, but in all cases the Pakistani
      community was over-represented, suggesting a high prevalence of inherited
      disease. The large numbers of affected children present a challenge, and adequate
      resources are needed to improve the delivery of counselling, treatment and care
      to the community. As child health in Pakistan improves, our experience with the
      UK Pakistani community suggests that the genetic causes of disability and disease
      in childhood will assume greater importance.

PMID- 14960894
TI  - Transcultural genetic counselling in the UK.
AB  - OBJECTIVES: Transcultural genetic counselling is not about being an expert on any
      given culture, rather it is a way of thinking about patients that acknowledges
      and values culture. Transcultural genetic counselling aims to provide a service,
      and to focus attention on aspects of the genetic counselling process which can
      easily be overlooked as we strive to improve the ways in which complex genetic
      information is delivered to all of the cultural groups we seek to serve. SUBJECTS
      AND METHODS: Two specific examples to illustrate particular problems will be
      given: (1) a UK Pakistani family with a lethal skin disorder and Down syndrome
      diagnosed prenatally, and (2) a Caucasian family who presented with a twin
      pregnancy and a history of infertility. RESULTS AND DISCUSSION: This article
      examines the way in which patients perceive and try to make sense of genetic
      diseases, the information given, and the course of action taken which may play a
      part in this process. We are also interested in how clinicians imagine the manner
      in which different cultures may influence the way they interact with patients.
      Genetic counsellors who view these differences as positive attributes will be
      most likely to meet, and resolve, the challenges that arise in transcultural
      genetic counselling.

PMID- 14960895
TI  - From knowledge to implementation.

PMID- 14960896
TI  - Teratology information services in Europe and their contribution to the
      prevention of congenital anomalies.
AB  - OBJECTIVES: To inform on Teratology Information Services (TIS) in Europe, their
      history, function and activity in preventing congenital malformations.
      CONCLUSIONS: Clinical teratology tries to identify human teratogens. TIS play an
      important role in public health by providing counsel on known reproductive risks
      and conducting specific research. This has led to a reduction in unnecessary
      fears of pregnant women and pregnancy terminations, as well as to better, more
      appropriate drug selection to treat acute or chronic disease. In addition, TIS
      units also conduct prospective studies and inform the public and physicians of
      the possible effects of environmental agents on the developing embryo and fetus.

PMID- 14960897
TI  - The use of birth defect registries for etiological research: a review.
AB  - BACKGROUND: Birth defect registries are often used for etiological research.
      Either as hypotheses-generating studies, or studies directed at one specific
      association between a risk factor and a birth defect in order to confirm or
      refute possible associations. METHODS: A literature search in Medline was
      performed looking for studies using birth defect registries for studying
      different risk factors. RESULTS: A brief summary of study design for etiological
      research with registration data is given. Subsequently, the different studies
      performed are discussed according to the risk factors investigated. Different
      aspects of the studies are listed and discussed. For each of the risk factors,
      the usefulness of birth defect registries to study the specific risk factor is
      discussed. Registries are dependent on the factors that are included in the
      registry or recorded in different databases. Most studies have looked at risk
      factors with readily available data, such as maternal age, illnesses and drugs.
      There is also wide use of other registers with exposure data on, for example, the
      environment. CONCLUSIONS: Birth defect registries have been used in the
      evaluation of many possible risk factors for birth defects. They have also been
      used in rebutting alarms in the media on possible clusters and risk factors.

PMID- 14960898
TI  - Prevention and detection of diabetic embryopathy.
AB  - Congenital anomalies are more common in the offspring of women with type 1 and
      type 2 diabetes mellitus. Herein we define those anomalies more commonly found in
      the offspring of women with diabetes mellitus, and examine the role of
      hyperglycemia in their pathogenesis. We then discuss methods for the optimal
      screening and detection of embryopathy. We conclude by presenting evidence in
      support of preconception diabetes care to lower the risk of fetal anomalies in
      women with diabetes mellitus.

PMID- 14960899
TI  - Antiepileptic drugs in pregnancy: options for the prevention of congenital
      abnormalities.
AB  - Maternal antiepileptic drug use during pregnancy is associated with an increased
      prevalence of congenital malformations in the offspring. This article describes
      the commonly known teratogenic effects of antiepileptic drugs. Options for
      primary and secondary prevention are discussed.

PMID- 14960900
TI  - The past and present practices and continuing controversies of preconception
      care.
AB  - Preconception care, a long-established concept for primary prevention of maternal
      and perinatal morbidity and mortality through detection and reduction of
      modifiable risks, has been widely propagated for the last decades. This article
      provides an overview of the various goals and practices described in the
      literature in different parts of the world, including issues and controversies
      pertaining to the provision and implementation of preconception care in different
      health care settings.

PMID- 14960901
TI  - Preventing congenital anomalies in developing countries.
AB  - The birth prevalence of congenital anomalies in developing countries is similar
      to that observed in developed countries. However, the health impact of birth
      defects is higher because of a lack of adequate services for the care of affected
      infants and a higher rate of exposures to infections and malnutrition. A number
      of successful measures for the prevention of congenital anomalies are being taken
      in a number of developing nations. Primary prevention programs are based on
      public education about preconceptional and prenatal risks. Prevention based on
      reproduction options includes teratogen information services and prenatal
      screening for fetal anomalies. In addition, programs for the detection of
      congenital malformations at birth, followed by early treatment, are contributing
      to secondary prevention. Prevention of congenital anomalies in the developing
      world requires: (a) good epidemiological data on the prevalence and types of
      birth defects and genetic disorders; (b) educating health professionals in the
      goals and methods of preventing birth defects at low cost but with high impact,
      and (c) expansion of family planning and improvement of antenatal care combined
      with educational campaigns to avoid the risks for birth defects. The basis for
      public health preventive measures should be the primary health care level. In a
      sizable proportion of developing countries, the stage is already set for these
      measures to be implemented. Required are education, political will, and proper
      organization and allocation of resources.

PMID- 14960902
TI  - Global prevention of all folic acid-preventable spina bifida and anencephaly by
      2010.
AB  - Folic acid-preventable spina bifida and anencephaly are pandemic, affecting
      225,000 children a year. These birth defects are as preventable as polio. As we
      near the eradication of polio, it is time to make the commitment to global
      prevention of all folic acid-preventable spina bifida and anencephaly (FA-P SBA)
      by 2010. Folic acid fortification of centrally processed foods, such as wheat and
      corn flour, could immediately prevent all of these birth defects for much of the
      world's population. These fortification programs will also help adults by
      increasing serum folate concentration, eradicating folate deficiency anemia,
      providing human genome stability and reducing homocysteine serum concentration,
      which will probably prevent heart attacks and strokes, and may prevent colon
      cancer and Alzheimer's disease. Where there is no centrally processed and
      distributed food to fortify, intense efforts must be made to increase consumption
      of synthetic folic acid through vitamin supplements. Geneticists can play a major
      role in preventing FA-P SBA by helping to create the political will in each
      country to implement fortification and supplement programs to eliminate disease
      caused by the current pandemic of folate deficiency.

PMID- 14960903
TI  - Physical and Chemical Factors in the Home and Workplace before and during
      Pregnancy.
AB  - OBJECTIVE: To present and discuss current knowledge about the relationship
      between physical and chemical factors in the home and workplace and adverse
      reproductive outcomes in the offspring. DESIGN AND METHODS: Critical review of
      the scientific literature, focusing mostly on epidemiological research. Reviews
      and original papers involving human occupational and home exposures to physical
      and chemical agents and their relation to adverse reproductive outcomes were
      screened and commented upon. RESULTS: Only a small proportion of the several
      thousands of occupational/home exposures have been adequately assessed for
      reproductive or developmental toxicity. This is reflected in the difficulties of
      identifying causal associations in humans and in the lack of data. CONCLUSION:
      According to present knowledge, very few authors confirmed that reproductive
      hazards exist in environmental agents, but increased surveillance of occupational
      exposures in relation to workers' reproductive health is highly desirable in
      order to assess moderate risks.

PMID- 14960904
TI  - Psychological impact of preconception counseling: assessment of anxiety before
      and during pregnancy.
AB  - OBJECTIVE: Assessment of anxiety levels in women and men before and after
      preconception counseling and during the first trimester of pregnancy. METHODS:
      Couples were recruited from the fertility clinic of the University Medical Center
      Nijmegen, the Netherlands. Anxiety was assessed using the 40-item Spielberger
      State-Trait Anxiety Inventory (STAI). RESULTS: 53 women and 51 men (74%)
      completed the STAI both before and after counseling. Anxiety levels did not
      change significantly after counseling or during the first trimester of pregnancy.
      83.4% would recommend preconception counseling to others. CONCLUSION:
      Preconception counseling is valued by the majority of women and men and does not
      lead to adverse psychological effects.

PMID- 14960905
TI  - Population-based estimates of the prevalence of family history of cancer among
      women.
AB  - OBJECTIVE: Family history of cancer is recognized as one of the most important
      risk factors in predicting personal cancer risk. Nevertheless, there are few
      published population-based estimates of family history prevalence by age
      categories. METHODS: We used responses of female controls (n = 4,754) from the
      population-based Cancer and Steroid Hormone study (1980-1982) to estimate the
      frequency of family history of various cancers among female relatives. We
      determined the age- and race-specific prevalence of family history of breast,
      ovarian, endometrial, and other cancers in first-degree female relatives of women
      aged 20-54 years. To evaluate changes in reporting family history over time, we
      also analyzed responses of control women (n = 1,544) from the Women's Interview
      Study on Health (WISH) (1990-1992) to estimate the prevalence of family history
      of breast cancer. RESULTS: The prevalence of a first-degree family history of
      breast, ovarian, endometrial, and cervical cancers was 6.4% (95% CI 5.7-7.1%),
      1.1% (0.8-1.4%), 3.5% (3.0-4.0%), and 2.1% (1.7-2.5%), respectively. Among first
      degree female relatives, the prevalence of family history of colon, lung, and
      thyroid cancers was 2.4% (2.1-2.9%), 1.5% (1.2-1.8%), and 0.5% (0.3-0.7%),
      respectively. The prevalence of family history of breast and colon cancers
      increased significantly with respondent's age. Similar results for family history
      of breast cancer were obtained from an analysis of responses from the WISH.
      CONCLUSIONS: In addition to providing a point of reference for research and
      health policy, these results may be of interest to providers who care for female
      patients because of the usefulness of information about family history of cancer
      for assessing lifetime risk of cancer.

PMID- 14960906
TI  - Opportunities for public health genetics trainees: results of an
      employer/workplace survey.
AB  - OBJECTIVE: To conduct the first employer/workplace survey identifying employment
      opportunities for graduates of programs with training in public health genetics
      in the USA, and to determine whether employment opportunities will increase in
      coming years. METHODS: Six public health genetics training competencies were
      developed. A survey about workplace and employment opportunities was then
      conducted with mailings to (1) departments in schools of public health and
      departments of preventive medicine, (2) local and regional public health
      officials, (3) insurance companies and health management organizations (HMOs),
      and (4) biotechnology and pharmaceutical companies. RESULTS: A total of 196
      surveys were returned among 1,464 that were mailed. Response rates varied from
      5.8 to 46.5% among the target groups. The percent of responding organizations
      currently employing individuals with skills in genetics ranged from 20 to 62%.
      The percent currently employing individuals with skills in public health ranged
      from 39 to 96%. Training opportunities such as internships or practicum
      experiences are reported for one-third of respondents. For all of the
      competencies, approximately half of survey respondents who rated the competency
      important or very important already employ individuals with public health
      genetics skills. Similarly, at least a quarter of survey respondents who rated
      the competency important or very important plan to hire individuals with that
      skill in the next 5 years. Overall, approximately 40% of those surveyed are
      planning to hire individuals with competencies in public health genetics in the
      next 5 years. CONCLUSION: Employment opportunities already exist and new
      positions are becoming available in schools of public health and departments of
      preventive medicine, departments of public health, insurance companies and HMOs
      for professionals with public health genetics training. Based on our survey
      findings, skills and training in public health genetics are important in the
      workplace.

PMID- 14960907
TI  - The frequency of inherited disorders database: prevalence of Huntington disease.
AB  - A database of the frequency of human inherited disorders is being established for
      use in a clinical context, in medical research, for epidemiological studies, and
      in the planning of genetic services. Each entry includes the disease name
      categorized by organ system, an Online Mendelian Inheritance in Man (OMIM)
      number, the mode of inheritance, the population origin, a prevalence and/or
      incidence rate and a literature reference. The Frequency of Inherited Disorders
      Database (FIDD) currently contains 1,580 entries relating to 280 different
      Mendelian disorders. FIDD will be prospectively maintained and can be accessed at
      http://www.uwcm.ac.uk/uwcm/mg/fidd/. A more refined and systematic literature
      search that will serve to expand the size, scope and scale of the database is
      currently in progress. The coverage of neurological and neuromuscular disorders
      is however considered to be nearly complete. In this first description of FIDD,
      Huntington disease was used to illustrate the structure and scope of the database
      as well as its potential scientific utility. A total of 100 published articles on
      the prevalence of Huntington disease were appraised. Prevalence and incidence
      rates varied between different ethnic groups and between different countries.
      Possible reasons for this variation are discussed.

PMID- 14960908
TI  - Participation in maternal marker screening for Down syndrome: contribution of the
      information delivered to the decision-making process.
AB  - OBJECTIVE: In France, health care providers now have to fulfill two requirements
      before serum marker screening for Down syndrome can be carried out: provide a
      written statement confirming that they informed the pregnant woman about the test
      and obtain the woman's written consent. A survey was designed to assess: (1)
      women's opinion on the explanations they received when the screening test was
      offered and when test results were given, and (2) the decisions women planned to
      make in light of the test results (i.e. to carry out amniocentesis or not).
      METHODS: The survey was intended for all French pregnant women who underwent the
      serum marker screening test during the first week of October 1998. The
      questionnaire was sent to women via clinical laboratories (3,825 questionnaires
      were sent to the 54 laboratories authorized for Down syndrome screening in
      France). Besides chi(2) tests and tests of comparisons of paired proportions, we
      conducted a hierarchical clustering analysis and qualitatively analyzed the free
      comments provided by women. RESULTS: The response rate was 39% (n = 1,473).
      Explanations given by the provider at the time the test was offered were not
      clear and ample enough for 38.8% of women. Furthermore, 45.9% of women stated the
      same opinion about the explanations provided with the test results. Based on the
      test results, amniocentesis was recommended to 125 high-risk women; 20.8% of them
      were going to decline the offer or had not yet decided. Among low-risk women, 13%
      requested amniocentesis or had not yet decided. The opinion of these high- or low
      risk women on the clarity and ampleness of the explanations provided with the
      test results was similar to that of high-risk women who wished to carry out
      amniocentesis. The hierarchical clustering analysis led us to identify clusters
      of women who mainly differed according to their opinion (anxious or reassured) on
      the explanations provided, regardless of their risk (high or low). CONCLUSION:
      Women's decision regarding screening for Down syndrome requires them to promptly
      integrate complex information on what the test is and entails. The question is
      then raised as to the type of information that is actually disclosed or that
      could be disclosed, based on how women value its contribution to decision-making.

PMID- 14960909
TI  - Reply to Prof. A. Lippman's commentary in the previous issue (4:87-89).

PMID- 14960911
TI  - Integrating genetic services into public health--guidance for state and
      territorial programs from the National Newborn Screening and Genetics Resource
      Center (NNSGRC).

PMID- 14960962
TI  - Long-term physical, mental, and functional consequences of abdominal
      decompression.
AB  - BACKGROUND: The long-term physical, mental, and functional consequences of
      abdominal decompression for intra-abdominal hypertension are unknown. METHODS:
      Thirty patients in various stages of abdominal decompression and delayed fascial
      closure for massive incisional hernia completed the SF-36 Health Survey and
      answered questions regarding their employment and pregnancy status. RESULTS:
      Patients awaiting abdominal wall reconstruction demonstrated significantly
      decreased perceptions of physical, social, and emotional health (p < 0.05),
      whereas patients who had completed definitive fascial closure demonstrated
      physical and mental health scores equivalent to the U.S. general population.
      Ultimately, 78% of patients employed before decompression returned to work.
      CONCLUSION: Abdominal decompression with skin grafting and delayed fascial
      closure initially decreases patient perception of physical, social, and emotional
      health, but subsequent abdominal wall reconstruction restores physical and mental
      health to that of the U.S. general population. Abdominal decompression does not
      prevent return to gainful employment and should not be considered a permanently
      disabling condition.

PMID- 14960963
TI  - The evolution of chest computed tomography for the definitive diagnosis of blunt
      aortic injury: a single-center experience.
AB  - BACKGROUND: Chest computed tomography (CT) is an excellent screening tool for
      blunt aortic injuries (BAIs). Aortography is considered the "gold standard" for
      diagnosis. Recent evidence suggests that new-generation, multislice, helical CT
      technology can accurately diagnose BAI. METHODS: A retrospective review of
      aortograms performed to evaluate for BAI was compared with the results of CT and
      operative findings. BAIs definitively diagnosed by CT alone were also studied.
      RESULTS: Between July 1, 1996, and June 30, 2002, 113 aortograms were obtained,
      with 28 BAI cases confirmed. Of these, 27 were congruently diagnosed by CT. Only
      one computed tomographic scan diagnostic for BAI had a subsequent negative
      aortogram. Seventeen BAIs were diagnosed with CT alone. Ten were confirmed
      operatively and seven were treated nonoperatively because of age, comorbid
      conditions, severity of injury, or the presence of small intimal defects.
      CONCLUSION: CT technology has evolved to allow for the definitive diagnosis and
      treatment of BAI. Aortography should still be used where new-generation CT is not
      available.

PMID- 14960964
TI  - Phosphomonoesters predict early mortality in porcine hemorrhagic shock.
AB  - BACKGROUND: Hemodynamic, laboratory, and tissue energetics were measured in a
      porcine model of hemorrhagic shock to evaluate variables as predictors of early
      mortality from shock. We hypothesized that elevated phosphomonoesters would
      predict early mortality in hemorrhagic shock. METHODS: Pigs (n = 36) were
      subjected to 35% hemorrhage for 90 minutes in a 1.5-T nuclear magnetic resonance
      (NMR) magnet. Measurements included base deficit (BD); lactate; oxygen
      consumption/delivery; near-infrared spectroscopy of liver, stomach, and skeletal
      muscle tissue oxyhemoglobin saturation; and NMR spectroscopic measurements of
      high-energy phosphates of liver and skeletal muscle. Variables were compared
      between nonsurvivors and survivors to resuscitation after 90-minute measurements.
      RESULTS: Ninety-minute mortality was 25%. Muscle phosphomonoesters (PMEs) and
      oxygen consumption differed significantly between survivors and nonsurvivors at
      baseline. Regression analysis identified baseline muscle PME levels, baseline BD,
      and 30-minute BD as early predictors of mortality before resuscitation (r2 =
      0.304). CONCLUSION: Baseline elevation in muscle PME levels predicts mortality in
      an animal model of severe hemorrhagic shock.

PMID- 14960965
TI  - Hepatocyte growth factor in polymorphonuclear leukocytes is increased in patients
      with systemic inflammatory response syndrome.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) has a significant effect on the
      regeneration of epithelial and endothelial cells. Studies have also shown an
      important role of HGF in wound healing and organ regeneration. Because recent
      studies indicate that polymorphonuclear leukocytes (PMNLs) store HGF in their
      specific granules and that HGF can be degranulated in the inflammatory tissue in
      which activated PMNLs migrate, we evaluated the storage and release of HGF in
      PMNLs from patients with systemic inflammatory response syndrome (SIRS) and
      attempted to examine the role of HGF from PMNLs in the systemic inflammatory
      process. METHODS: Twenty-four patients with SIRS (serum C-reactive protein, 20.2
      +/- 12.4 mg/dL [mean +/- SD]) and 18 healthy volunteers were studied. HGF in
      PMNLs was measured by flow cytometry by using a monoclonal antibody to HGF. The
      oxidative activity in PMNLs was also measured by flow cytometry. Serum HGF,
      interleukin (IL)-6, and IL-8 levels in each patient were measured by enzyme
      linked immunosorbent assay. HGF degranulation from PMNLs was evaluated in 10
      patients. RESULTS: Immunocytochemistry under fluorescence microscopy revealed
      enhanced expression of HGF in the granules of PMNLs. HGF in PMNLs significantly
      increased in patients with SIRS compared with PMNLs from healthy volunteers
      (SIRS, 171.0 +/- 6.6 fluorescence/cell; control, 130.7 +/- 3.8
      fluorescence/cell). N-formylmethionyl-leucyl-phenylalanine and lipopolysaccharide
      stimulation induced further increase of HGF fluorescence in PMNLs from patients.
      HGF degranulation from PMNLs was also significantly enhanced in patients.
      Moreover, oxidative activity in PMNLs was significantly enhanced in patients with
      SIRS. Plasma HGF (pHGF) correlated positively with IL-6 and IL-8 levels in
      patients (pHGF and IL-6, gamma = 0.635, p < 0.05; pHGF and IL-8, gamma = 0.827, p
      < 0.01), but these values did not correlate with HGF in PMNLs. CONCLUSION:
      Activated PMNLs in SIRS patients increased HGF in their granules and demonstrate
      enhanced degranulation of HGF. The release of HGF from migrated PMNLs in the
      inflammatory tissue may play an important role in wound healing and organ
      regeneration under those conditions.

PMID- 14960966
TI  - Beta-blocker use is associated with improved outcomes in adult burn patients.
AB  - BACKGROUND: There is no direct evidence that beta-blockers improve mortality in
      burn victims. Beta-blockers attenuate hypermetabolic states in burned children,
      and perioperative use in elective adult cases has beneficial effects, which
      suggests that beta-blockers may also improve burn outcomes. However, beta
      blockers decrease cardiac output and may decrease oxygen delivery, and
      theoretically may increase mortality. What is the effect of beta-blockers on
      healing time and mortality in burn patients? METHODS: This was a retrospective
      cohort study. We identified three cohorts of adult burn patients between 1996 and
      2001: all who were on beta-blockers (BB) before their injury (PMH BB); all who
      were initiated on BB during their hospitalization for management of hypertension
      or tachyarrhythmia (HOSP BB); and control, who were never treated with beta
      blockers. For each patient in the PMH BB and HOSP BB groups, two patients were
      placed in the control cohort by matching age and total body surface area burn.
      Premorbid conditions such as diabetes, hypertension, cardiac disease, renal
      insufficiency, and diuretic and calcium channel blocker use were analyzed.
      Multivariate regression models were used to identify independent modifiers.
      RESULTS: There were 21 PMH BB, 22 HOSP BB, and 86 control patients. All PMH BB
      patients remained on their BB regimen in the hospital. HOSP BB patients were
      initiated on beta-blockers at a mean of 8.8 days postinjury. There were no
      differences in age (mean, 58 +/- 17 years), total body surface area burned (mean,
      14 +/- 12%), or mechanism of injury among the cohorts. The mortality rate was 5%
      for the PMH BB cohort, 27% for the HOSP BB cohort, and 13% for controls. The mean
      healing times were 51 +/- 29 days for PMH BB patients, 79 +/- 54 days for HOSP BB
      patients, and 60 +/- 39 for controls. In multivariate analyses, PMH BB was
      associated with a significant decrease in fatal outcome and healing time (p < or
      = 0.05 compared with control). CONCLUSION: Beta-blockers have the potential to
      improve adult burn outcomes. Postinjury treatment should be studied in a
      randomized, clinical trial.

PMID- 14960967
TI  - Burn injury and pulmonary sepsis: development of a clinically relevant model.
AB  - BACKGROUND: Despite improvements in the early resuscitation of the critically
      injured, mortality from multiple organ failure has remained stable, with the lung
      often the first organ to fail. Early intubation and mechanical ventilation
      predispose patients to the development of pneumonia and respiratory failure. Our
      objective was to establish a murine model of combined injury, consisting of
      burn/trauma and pulmonary sepsis with reproducible end-organ responses and
      mortality. METHODS: Male B6D2F1 mice were divided into four groups:
      burn/infection (BI), burn (B), infection (I), and sham (S). Burned animals had a
      full-thickness 15% dorsal scald burn. BI and I groups were inoculated
      intratracheally with Pseudomonas aeruginosa (3-5 x 103 colony-forming units). S
      and B animals received saline intratracheally. All animals were resuscitated with
      2 mL of intraperitoneal saline. Mortality was recorded at 24, 48, and 72 hours.
      Bacterial sepsis was confirmed by tissue Gram's stain of the lungs and positive
      organ and blood cultures for Pseudomonas aeruginosa. Femoral bone marrow cells
      were collected at 72 hours from surviving animals. Clonogenic potential was
      assessed by response to macrophage (M) colony-stimulating factor (CSF) and
      granulocyte-macrophage (GM) CSF in a soft agar assay and the data were
      represented as colonies per femur. Isolated alveolar macrophages and whole lung
      tissue were assayed for levels of the inflammatory cytokines tumor necrosis
      factor-alpha and interleukin-6. RESULTS: Mortality at 72 hours was 30% in BI, 12%
      in I, and <10% in B and S groups. Pneumonia was documented in all infected
      animals at 24 hours by Gram's stain and positive tissue cultures for Pseudomonas
      aeruginosa. Systemic sepsis as confirmed by blood, and remote organ cultures was
      seen in BI animals only. Significantly increased responsiveness to M-CSF
      stimulations was noted in all groups (BI, 8,291 +/- 1,402 colonies/femur; B,
      6,357 +/- 806 colonies/femur; and I, 8,054 +/- 1,112 colonies/femur; p < 0.05)
      relative to sham (3,369 +/- 883 colonies/femur, p < 0.05). Maximal responsiveness
      to GM-CSF stimulation was noted in the BI group (11,932 +/- 982 colonies/femur, p
      < 0.05), and similar GM responsiveness was noted in all other groups (B, 7,135 +/
      548 colonies/femur; I, 7,023 +/- 810 colonies/femur; and S, 6,829 +/- 1,439
      colonies/femur). Alveolar macrophage release of the proinflammatory cytokines
      tumor necrosis factor-alpha and interleukin-6 increased in all animals, but the
      magnitude of increase was not proportional to the strength of the inciting
      stimulus. CONCLUSION: Although minimal perturbations were seen after burn or
      pulmonary infection alone, the combined insult of burn and pulmonary sepsis
      resulted in statistically significant hematopoietic changes with increased
      monocytopoiesis. Only the combined injury resulted in systemic sepsis and
      significantly increased mortality. We have developed a clinically relevant model
      of trauma and pulmonary sepsis that will allow further clarification of the
      inflammatory response after injury and infection.

PMID- 14960968
TI  - Small volume albumin administration protects against hemorrhagic shock-induced
      bone marrow dysfunction.
AB  - BACKGROUND: Unexpected immunomodulatory effects of colloids and crystalloids
      prompted an investigation of albumin's ability to prevent bone marrow (BM)
      suppression following trauma/hemorrhagic shock (T/HS: laparotomy + MAP 30 for 90
      mins). METHODS: In vitro: Normal rat BM was plated for granulocyte-macrophage
      (CFU-GM) and erythrocyte colony forming units (BFU-E) with 2% v/v plasma from
      sham (T/SS) or T/HS rats and albumin (2-8 mg/mL). In vivo: Male rats (n =
      4/group) were subjected to T/SS or T/HS and resuscitated with shed blood and
      twice the volume as Lactated Ringer's (LR) or blood and 1, 2, or 3 mL of albumin
      (50 mg/mL). Bone marrow harvested 3 hours post-resuscitation was plated for CFU
      GM and BFU-E. RESULTS: In vitro: T/HS plasma decreased both CFU-GM and BFU-E
      growth as compared with T/SS, whereas increasing doses of albumin showed dose
      dependent improvement in progenitor growth (p < 0.05). In vivo: The suppression
      of BM red and white cell progenitor growth seen in T/HS+LR rats as compared with
      T/SS was fully prevented by as little as 1 mL of albumin (p < 0.05). CONCLUSIONS:
      Small doses of albumin fully restore CFU-GM and BFU-E to sham values. We
      postulate that the binding of circulating toxic factors by albumin may play a
      role in this prevention of T/HS-induced BM suppression.

PMID- 14960969
TI  - The impact of major trauma: quality-of-life outcomes are worse in women than in
      men, independent of mechanism and injury severity.
AB  - BACKGROUND: The importance of gender differences in quality of life and
      psychologic morbidity after major trauma is a newly recognized focus of trauma
      outcomes research. The Trauma Recovery Project is a large, prospective,
      epidemiologic study designed to examine multiple outcomes after major trauma,
      including quality of life (QoL), and psychologic sequelae such as depression and
      early symptoms of acute stress reaction (SASR). The specific objectives of the
      present report are to examine gender differences in QoL outcomes and the early
      incidence of combined depression and SASR after injury, controlling for injury
      severity, specific body area injured, and mechanism. METHODS: Between December 1,
      1993, and September 1, 1996, 1,048 eligible trauma patients triaged to four
      participating trauma center hospitals in the San Diego Regionalized Trauma System
      were enrolled in the study. The enrollment criteria for the study included age 18
      years and older, admission Glasgow Coma Scale score of 12 or greater, and length
      of stay greater than 24 hours. QoL outcome after trauma was measured after injury
      using the Quality of Well-being scale, a sensitive index to the well end of the
      functioning continuum (range, 0 = death to 1.000 = optimum functioning).
      Depression was assessed using the Center for Epidemiologic Studies scale. SASR
      was assessed using the Impact of Events scale. Patient outcomes were assessed at
      discharge and at 6, 12, and 18 months after discharge. RESULTS: Women (n = 313)
      were significantly more likely to have poor QoL outcomes at follow-up than men (n
      = 735) (women vs. men: 12-month follow-up odds ratio [OR] = 2.2, p < 0.001; 18
      month follow-up OR = 2.0, p < 0.001). Quality of Well-being scores at each of the
      6-, 12-, and 18-month follow-up time points were markedly and significantly lower
      in women compared with men, independent of injury severity, serious and moderate
      injury status, lower extremity injury, intentional or unintentional injury type,
      and blunt or penetrating injury. Women were also significantly more likely to
      develop early combined depression and SASR at discharge (OR = 1.7, p < 0.01) and
      to have continuous depression throughout the 18-month follow-up period (OR = 2.3,
      p < 0.001). CONCLUSION: These analyses provide further important and more
      detailed evidence that women are at risk of worse QoL outcomes and early
      psychologic morbidity after major trauma than men, independent of mechanism and
      injury severity. A better understanding of the impact of major trauma in men and
      women will be an important component of efforts to improve trauma care and long
      term outcome in mature trauma systems.

PMID- 14960970
TI  - Formalized radiology rounds: the final component of the tertiary survey.
AB  - BACKGROUND: An important objective of organized trauma care is to minimize
      delayed diagnoses and missed injuries. Discrepant interpretations of radiographs
      initially read by trauma surgeons represent a unique source of delayed diagnoses.
      The purpose of this study was to evaluate the efficacy of formalized radiology
      rounds as a component of the tertiary survey. METHODS: Over an 18-month period,
      432 consecutive patients admitted to the trauma service at a Level II trauma
      center were studied prospectively. Radiographs obtained as part of the initial
      evaluation were initially interpreted by an attending trauma surgeon. All
      radiographs from the previous 24-hour admissions were reviewed by the trauma team
      with an attending radiologist at radiology rounds. New diagnoses (NDx) were
      defined as radiographic findings identified at radiology rounds that were not
      recorded by the trauma surgeon at the time of initial evaluation. The clinical
      significance of any NDx was described as follows: level 1, NDx resulted in
      significant morbidity/mortality; level 2, NDx resulted in alteration in care/no
      morbidity; level 3, NDx resulted in no alteration in care; level 4, NDx was an
      incidental finding by the radiologist; level 5, NDx by radiologist not definite.
      RESULTS: Forty-seven NDx were identified in 42 patients (9.7%). Of the 47 NDx, 19
      (40.4%) were level 3 and 28 (59.6%) were level 2. No level 1 NDx were identified.
      Forty-four changes in clinical management were documented in the level 2 group.
      Eight new consults were ordered in seven patients (16.7%): orthopedic surgery (n
      = 6), neurosurgery (n = 1), and physical therapy (n = 1). Seventeen additional
      diagnostic procedures were required in 16 patients (38.1%): plain radiographs (n
      = 11) and computed tomographic scans (n = 6). Nineteen therapeutic changes were
      required in 16 patients (38.1%): splint/immobilization device (n = 7), modified
      level of activity (n = 6), surgical procedures (n = 4), transfer (n = 1), and
      home equipment (n = 1). CONCLUSION: A small number of radiographic findings are
      not detected by trauma surgeons during the initial evaluation. Although these
      findings are not of major clinical significance, the majority required some
      alteration in care plan. Formalized radiology rounds promotes clinical efficiency
      through early identification of these injuries, which facilitates any necessary
      alteration in the care plan.

PMID- 14960971
TI  - A time-dependent analysis of intensive care unit pneumonia in trauma patients.
AB  - BACKGROUND: Appropriate and timely antibiotic therapy to treat pneumonia in
      trauma patients is extremely important. We evaluated the incidence and
      microbiology of pneumonia stratified by days postadmission and risk factors.
      METHODS: Prospective data were collected on 714 trauma patients admitted to the
      intensive care unit over a 1-year period. Pneumonia was classified as community
      acquired (CAP) (< or = 3 days), early nosocomial (ENP) (4-6 days), or late
      nosocomial (LNP) (> or = 7 days). In addition, pneumonia was classified as CAP
      only, nosocomial only (NI), or combination (CAP and NI, or ENP and LNP)
      pneumonia. Strict institutional guidelines were followed for diagnosis. RESULTS:
      One hundred eighty-two patients (25%) were diagnosed with 204 pneumonias over the
      study period. One hundred twenty-five (61%) of these pneumonias were ventilator
      associated. Staphylococcus aureus and Haemophilus influenzae were the most common
      pathogens isolated. Twenty-one percent of patients with CAP acquired an LNP (p <
      0.025), in which Pseudomonas was the most common organism. Haemophilus caused LNP
      in 12% of patients. Cancer (p < 0.01), liver failure (p < 0.05), and age (p <
      0.01) were predictive of nontypical pathogens in patients with CAP and ENP (p <
      0.05). Obesity was most predictive of increased ventilator days (p < 0.001) and
      intensive care unit length of stay (p < 0.001). Increased age, alcohol abuse, and
      field airway were most predictive of mortality. CONCLUSION: Unanticipated
      pathogens were isolated in each class of pneumonia. The clinician must be aware
      of significant risk factors that may predispose patients to pathogens that are
      not ordinarily covered with standard antibiotic therapy.

PMID- 14960972
TI  - Analysis of 162 colon injuries in patients with penetrating abdominal trauma:
      concomitant stomach injury results in a higher rate of infection.
AB  - BACKGROUND: Fecal contamination from colon injury has been thought to be the most
      significant factor for the development of surgical site infection (SSI) after
      trauma. However, there are increasing data to suggest that other factors may play
      a role in the development of postinjury infection in patients after colon injury.
      The purpose of this study was to determine the impact of gastric wounding on the
      development of SSI and nonsurgical site infection (NSSI) in patients with colon
      injury. METHODS: Post hoc analysis was performed on data prospectively collected
      for 317 patients presenting with penetrating hollow viscus injury. One hundred
      sixty-two patients with colon injury were subdivided into one of three groups:
      patients with isolated colon wounds (C), patients with colon and stomach wounds
      with or without other organ injury (C+S), and patients with colon and other organ
      injury but no stomach injury (C-S) and assessed for the development of SSI and
      NSSI. Infection rates were also determined for patients who sustained isolated
      gastric injury (S) and gastric injury in combination with other injuries other
      than colon (S-C). Penetrating Abdominal Trauma Index, operative times, and
      transfusion were assessed. Discrete variables were analyzed by Cochran-Mantel
      Haenszel chi2 test and Fisher's exact test. Risk factor analysis was performed by
      multivariate logistic regression. RESULTS: C+S patients had a higher rate of SSI
      infection (31%) than C patients (3.6%) (p=0.008) and C-S patients (13%)
      (p=0.021). Similarly, the incidence of NSSI was also significantly greater in the
      C+S group (37%) compared with the C patients (7.5%) (p=0.07) and the C-S patients
      (17%) (p=0.019). There was no difference in the rate of SSI or NSSI between the C
      and C-S groups (p=0.3 and p=0.24, respectively). The rate of SSI was
      significantly greater in the C+S patients when compared with the S-C patients
      (31% vs. 10%, p=0.008), but there was no statistical difference in the rate of
      NSSI in the C+S group and the S-C group (37% vs. 24%, p=0.15). CONCLUSION: The
      addition of a gastric injury to a colon injury has a synergistic effect on the
      rate of postoperative infection.

PMID- 14960973
TI  - Computed tomographic scanning without oral contrast solution for blunt bowel and
      mesenteric injuries in abdominal trauma.
AB  - BACKGROUND: Computed tomographic (CT) scanning using intravenous and oral
      contrast material has traditionally been advocated for the evaluation of intra
      abdominal injury, including blunt bowel and mesenteric injuries (BBMIs). The
      necessity of oral contrast in detecting these injuries has recently been called
      into question. The purpose of this study was to determine the sensitivity and
      specificity of CT scanning without oral contrast for BBMIs. METHODS: We
      prospectively enrolled 500 consecutive blunt trauma patients who received CT
      imaging and interpretation (CT-Read1) of the abdomen from July 2000 to November
      2001. All patients were imaged without oral contrast, but with intravenous
      contrast. CT images were reviewed within 24 hours of admission by a research
      radiologist (CT-Read2) blinded to CT-Read1. For study purposes, true BBMI was
      determined to be present if either laparotomy or autopsy identified bowel or
      mesenteric injury, or both CT-Read2 and the hospital discharge summary described
      bowel or mesenteric injury. Three-month telephone follow-up was also completed.
      RESULTS: CT-Read1 detected 19 of 20 bowel and mesenteric injuries. CT-Read1
      missed one duodenal perforation. There were two patients with false-positive
      interpretations of CT-Read1 for bowel injury. The sensitivity and specificity of
      CT imaging for the detection of BBMIs were 95.0% and 99.6%, respectively.
      CONCLUSION: CT imaging of the abdomen without oral contrast for detection of
      BBMIs compares favorably with CT imaging using oral contrast.

PMID- 14960974
TI  - Intestinal and multivisceral transplantation after abdominal trauma.
AB  - SUMMARY: BACKGROUND Some trauma victims who survive acute illness develop
      lingering, debilitating syndromes that are incompatible with any semblance of
      normalcy. Intestinal failure, in particular, exacts a high price in terms of
      quality of life. Total parenteral nutrition (TPN) has served these patients well,
      but complications limit its long-term therapeutic effect. Consequently,
      transplantation is emerging as a life-saving therapy for some patients with the
      short gut syndrome. METHODS We reviewed eight adult and two pediatric recipients
      of intestinal and multivisceral transplants after severe abdominal trauma.
      Background demographics, type of abdominal trauma, transplant procedure,
      postoperative complications, and survival rates were appraised. This group was
      also compared with 47 nontrauma recipients of intestinal transplants performed
      during the same period. RESULTS Four patients (40%) died postoperatively
      (postoperative days 7, 53, 87, and 91) as a result of multiple organ failure
      after graft pancreatitis (n = 1), viral encephalitis (n = 1), and sepsis after
      severe rejection (n = 2). Six patients (60%) are alive (postoperative days 52
      1,783). All are off TPN. The 4-year patient survival was 58%, with no significant
      difference between trauma and nontrauma patients.CONCLUSION Intestinal and
      multivisceral transplantation are viable options for the treatment of
      irreversible intestinal failure associated with severe trauma. Surviving patients
      are TPN independent and have a satisfactory quality of life.

PMID- 14960975
TI  - Variation in the management of pediatric splenic injuries in New England.
AB  - BACKGROUND: Nonoperative management of stable children with splenic injuries is
      the standard of care but has been variably applied in New England. The influence
      of surgeon training on this variation was analyzed. METHODS: A region-wide
      administrative data set was queried for children with a splenic injury from 1990
      through 1998. The influence of a range of patient- and hospital-specific
      variables, including surgeon pediatric training, on the risk of operation was
      analyzed. RESULTS: The risk of operation increased with age, severity of splenic
      injury, and the presence of multiple injuries, but also trauma center status and
      the presence of a surgical training program. After allowance for these variables,
      the risk of operation was reduced by half when children with splenic injuries
      were cared for by a surgeon with pediatric specialty training. CONCLUSION: The
      risk of operation for pediatric splenic injury in New England is dependent on
      several variables, including the surgeon's training.

PMID- 14960976
TI  - Inter- and intrarater reliability in computed axial tomographic grading of
      splenic injury: why so many grading scales?
AB  - OBJECTIVE: After splenic trauma, critical decisions regarding operative
      intervention are often made with the aid of computed axial tomographic (CT) scan
      findings. No CT scan-based grading scale has been demonstrated to predict
      accurately which patients require operative or radiologic intervention for their
      splenic injuries. We hypothesized that use of the most common grading scale, the
      American Association for the Surgery of Trauma scale, would be associated with
      low intra- and interreliability scores. We assessed the ability of experienced
      trauma radiologists to differentiate grade III from grade IV splenic injuries.
      METHODS: The films of patients who had undergone abdominal CT scanning before
      splenectomy for grade III or IV injuries were serially evaluated by four trauma
      radiology faculty weekly for 3 weeks. We assessed intra- and interrater
      reliability for grading and for presence of contrast blush. RESULTS: Intrarater
      reproducibility yielded a weighted kappa score of 0.15 to 0.77. Interrater
      reliability weighted kappa scores ranged from 0 to 0.84, with a mean value of
      0.23. CONCLUSION: CT imaging is not reliable for identifying grades III and IV
      splenic injury, as experienced radiologists often underestimate the magnitude of
      injury. Interrater reliability is poor. Factors other than the CT grade of
      splenic injury should determine whether patients require operative or
      angiographic therapy.

PMID- 14960977
TI  - Documentation of posttraumatic nerve compression in patients with normal
      electrodiagnostic studies.
AB  - BACKGROUND: Electrodiagnostic evaluation may suggest the absence of posttraumatic
      nerve compression in the presence of patient symptoms. Computer-assisted
      neurosensory testing documents peripheral nerve sensory impairment. In the
      setting of trauma, where there are often legal implications, documentation of
      peripheral nerve compression is important. This is highlighted in the diabetic,
      who may have neuropathy. METHODS: A prospective study tracked trauma-related
      peripheral nerve problems in patients with "normal" electrodiagnostic studies,
      and for whom surgical care or legal outcome was determined by documentation of
      abnormalities by testing with the Pressure-Specified Sensory Device. Eight
      patients were identified, four of whom had diabetes. RESULTS: In all eight
      patients, neurosensory testing documented peripheral nerve problems, which was
      critical in obtaining approval from workers' compensation insurance carrier for
      decompression of the nerve and facilitating legal settlement. CONCLUSION:
      Neurosensory testing with the Pressure-Specified Sensory Device identifies
      peripheral nerve compression related to trauma, facilitating management of the
      patient, even in the presence of diabetic neuropathy.

PMID- 14960978
TI  - Effect of intercostal nerve block with 0.5% bupivacaine on peak expiratory flow
      rate and arterial oxygen saturation in rib fractures.
AB  - BACKGROUND: This prospective study was undertaken to evaluate the efficiency of
      intercostal nerve block (ICNB) with 0.5% bupivacaine (Marcaine) for pain relief
      in patients with rib fractures and to correlate the degree of pain relief with
      changes in the peak expiratory flow rate (PEFR) and oxygen saturation (Sao2).
      METHODS: Twenty-one consecutive adult patients admitted with rib fractures
      associated with severe pain formed the basis of the study. Chest pain was scored
      on a four-point scale before ICNB, 1 hour after ICNB, and 24 hours after ICNB.
      Sao2 was measured before and immediately after ICNB. PEFR was measured before and
      immediately after ICNB. RESULTS: Pain score and PEFR before and after ICNB showed
      statistically significant differences (p = 0.0000, df = 20). There was a
      significant difference between Sao2 before and after ICNB. CONCLUSION:
      Significant increases in Sao2 and PEFR occur after ICNB with 0.5% bupivacaine,
      which also provides sustained analgesia, leading to improvement in respiratory
      mechanics.

PMID- 14960979
TI  - Thoracolumbar fractures in patients with multiple injuries: diagnosis and
      treatment-a review of 147 cases.
AB  - BACKGROUND: The initial evaluation and treatment of patients with multiple
      injuries are challenging. However, little is known about thoracolumbar fractures
      in patients with multiple injuries. We aimed to determine the incidence of missed
      injuries of the thoracolumbar spine in patients with multiple injuries, to
      examine the reasons for the delay in diagnosis, and to study the selection of
      treatment options in the management and timing of surgical intervention. METHODS:
      One hundred forty-seven consecutive patients with acute thoracolumbar fractures
      and multiple trauma at the authors' hospital between 1988 and 1997 were
      retrospectively reviewed. The incidence of missed injuries of the thoracolumbar
      spine and the reasons for the delay in diagnosis were determined. All these
      patients were observed for a minimum of 3 years after surgery, except four who
      died during their hospital stay. RESULTS: Delayed diagnosis of thoracolumbar
      fractures was made in 28 patients (19%). There was an increased incidence of
      pulmonary complications (p < 0.01) and increased length of hospital stay (p <
      0.05) in patients treated nonoperatively compared with patients treated
      operatively. Although no significant differences in the recovery rate of
      neurologic function (p > 0.05) were noted between the groups, the surgical
      patients had highly significantly less pain compared with the nonoperative
      patients (p < 0.01). The relationship between the timing of thoracolumbar surgery
      and complications failed to show statistical significance (p > 0.05). Neither the
      severity of injury nor the timing of surgery had any significant effect on the
      recovery rate (p > 0.05). CONCLUSION: Patients with blunt trauma caused by high
      energy impact injuries are much more likely to have thoracolumbar fractures even
      if injuries elsewhere have been noted. Further radiographic studies of the
      thoracolumbar spine should be performed if there is any question related to a
      thorough and systematic examination. Choice of treatment options of thoracolumbar
      fractures in patients with multiple injuries is not different from that in
      patients with no associated injuries to other systems. Appropriate timing of
      thoracolumbar fracture fixation in patients with multiple injuries should not be
      dependent on a rigid protocol.

PMID- 14960980
TI  - Continuous pulse oximeter monitoring for inapparent hypoxemia after long bone
      fractures.
AB  - BACKGROUND: Continuous pulse oximeter monitoring (CPOM) and daily intermittent
      arterial blood gas (ABG) were used to define the incidence, pattern, and severity
      of inapparent hypoxemia after long bone fractures. METHOD: Twenty long bone
      fracture patients and 19 normal control patients were studied. CPOM, daily ABG,
      hypoxic symptoms, and features of fat embolism syndrome were monitored for 72
      hours after fractures and after surgical interventions. RESULTS: CPOM trend
      curves showed that all fracture patients except one had recurrent desaturations
      below 90% Sao2 of varying duration and depth. The lowest Sao2 was down to 60% and
      the longest episode lasted for 1.47 hours. ABG analysis could not show the
      recurrent phenomena and never detected the corresponding desaturation episodes.
      Long bone fracture patients had more desaturation episodes, longer total
      desaturation duration, and larger total area under desaturation curves in both
      the postfracture and postoperative periods (p < 0.05). The mean Sao2 was
      significantly lower in the postfracture period. Although most patients remained
      asymptomatic and recovered spontaneously, two required transient oxygen therapy
      and one progressed to fat embolism syndrome. CONCLUSION: Inapparent hypoxia with
      profound desaturation is common after long bone fractures. CPOM of all patients
      admitted with long bone fractures is recommended for early detection. In patients
      who develop inapparent hypoxia, additional pulmonary insult should be avoided or
      undertaken with care and well timed.

PMID- 14960981
TI  - Bone debris: dead matter or vital osteoblasts.
AB  - BACKGROUND: Mechanical manipulation, pressure, and temperature increase can
      induce bone necrosis during intramedullary reaming. METHODS: In this study, the
      bone debris obtained after reaming 18 sheep tibiae was analyzed to investigate
      its vitality by measuring alkaline phosphatase activity. Two different reamer
      designs were used for the project. Bone cells were first cultivated in a specific
      growth medium, counted 3 weeks after the reaming procedure, and then cultivated
      for another 5 weeks. RESULTS: At the end of the project, qualitative evaluation
      showed positive alkaline phosphatase activity in most of the cases, and
      quantitative evaluation also showed enzyme activity. The positive alkaline
      phosphatase results were independent of the reamer sizes and reamer design. No
      significant results were obtained from a comparison of different reamer sizes and
      designs. This indicates that osteoblasts survive after correctly performed
      reaming. CONCLUSION: The results prove the vitality of the bone debris and
      confirm clinical observations.

PMID- 14960982
TI  - Bone transport in the management of posttraumatic bone defects in the lower
      extremity.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical and functional
      outcomes of traumatic bone defects of the lower extremity managed by internal
      bone transport using the Ilizarov technique. METHODS: We retrospectively reviewed
      19 patients who underwent internal bone transport for traumatic bone defects in
      the lower extremity. Mean follow-up was 68.7 months (5.7 years). Eighteen cases
      were open: grade IIIA, 10 cases; grade IIIB, 4 cases; and grade IIIC, 4 cases.
      RESULTS: Clinical outcome was 2 excellent, 11 good, 4 fair, and 2 poor. Eighteen
      of 19 patients reported being satisfied. The results of the SF-36 Health Survey
      showed a significant difference between the population norm and the mean of the
      study group in Physical Functioning, Bodily Pain, and Role-Emotional. The mean
      length of time in external fixation for all patients was 13.8 months. The mean
      length of regenerate was 5.7 cm (range, 0.8-20.4 cm). The total number of
      complications was 39 (20 minor and 19 major). Major complications included two
      transtibial amputations and four fractures at the docking site. CONCLUSION:
      Although the number of complications was high, the patients in this study were
      satisfied to have their limbs preserved. The SF-36 Health Survey showed that
      patients suffer mainly from physical and emotional consequences after these major
      injuries. Their general, social, and mental health is usually not affected.
      Infection significantly increased the healing index. The limb should be protected
      for a long time, with careful evaluation to avoid fracture at the docking site
      after fixator removal.

PMID- 14960983
TI  - Modulation of microvascular hydraulic permeability by platelet-activating factor.
AB  - BACKGROUND: Platelet-activating factor (PAF) is a modulator of the inflammatory
      response to shock. Edema formation and intravascular fluid loss have been
      associated with PAF. The increase in microvessel permeability caused by PAF may
      be related to direct endothelial cell activation and leukocyte activation. We
      hypothesized that PAF increases hydraulic permeability by means of the direct
      activation of endothelial cells. METHODS: Hydraulic permeability (Lp) was
      measured in rat mesenteric venules using the modified Landis micro-occlusion
      technique. After baseline Lp measurements, paired measures of Lp were obtained
      during PAF perfusion at doses of 0.1 nmol/L (n = 6), 1.0 nmol/L (n = 6), 10
      nmol/L (n = 6), and 50 nmol/L (n = 6). The temporal effects of pulse
      administration of PAF and repeated exposures to PAF were also assessed. RESULTS:
      Compared with baseline values (Lp = 1.16 +/- 0.11), the Lp of the microvessels
      significantly increased at PAF doses of 0.1 nmol/L (Lp = 1.46 +/- 0.1) (p <
      0.002), 1 nmol/L (Lp = 2.0 +/- 0.11) (p < 0.004), 10 nmol/L (Lp = 4.09 +/- 0.09)
      (p < 0.005), and 50 nmol/L (Lp = 5.13 +/- 0.07) (p < 0.0001). All units for Lp
      are given as +/- SE x 10 -7 cm s-1. cm H2O-1. CONCLUSION: PAF increased
      microvessel permeability in a dose-dependent manner. The permeability-increasing
      effect of PAF was transient even with continuous endothelial exposure to PAF.
      This study emphasizes the ability of PAF to directly modulate microvascular
      permeability and increase venular permeability.

PMID- 14960984
TI  - Low-dose prostacyclin restores an increased protein permeability after trauma in
      cat skeletal muscle.
AB  - BACKGROUND: Increased microvascular permeability inducing leakage of plasma from
      the intravascular to the extravascular space after trauma is a pathophysiologic
      event of great clinical significance. A substance reducing an increased
      microvascular permeability, and especially an increased protein permeability,
      therefore could be of value to maintain normovolemia and to reduce the need for
      plasma substitution. Prostacyclin is suggested to have permeability-reducing
      properties as shown for fluid permeability, but its effects on protein
      permeability, which may be controlled by partly different mechanisms, are
      unclear. The present study evaluates whether prostacyclin at a low, clinically
      relevant, nonvasodilating dose can reestablish an increased protein permeability
      after trauma. METHODS: The study was randomized, blinded, and performed on
      surgically traumatized, autoperfused, and denervated cat calf muscle. Relative
      changes in the osmotic reflection coefficient for albumin after 1.5 hours of
      prostacyclin (1 ng/min/kg) (n = 7) or vehicle (n = 7) treatment were used as a
      measure of altered protein permeability from a state of increased permeability
      after trauma. RESULTS: We found that the osmotic reflection coefficient for
      albumin was increased by about 35% in the prostacyclin group compared with the
      vehicle-treated group (p < 0.001). CONCLUSION: If applicable to humans,
      prostacyclin is a potential therapy for reducing plasma leakage in the critically
      ill trauma patient by restoring permeability from an increased level.

PMID- 14960985
TI  - Neuroprotective role of aminoguanidine in behavioral changes after blast injury.
AB  - BACKGROUND: The present study investigated the neuroprotective role of
      aminoguanidine, a known inducible nitric oxide synthase inhibitor, in both
      behavioral and morphologic changes in rats subjected to nonpenetrative blast
      injury. METHODS: Male Sprague-Dawley rats were randomly divided into groups to
      receive either normal saline or aminoguanidine (AG) before or after exposure to
      two blast dosages of either 2.8 or 20 kPa. The neurobehavioral alterations were
      determined by subjecting the animals to rotametric, grip-strength, passive
      avoidance, total and ambulatory locomotor activities, and acoustic startle
      response tests. RESULTS: Exposure to blast at 20 kPa resulted in a significant
      performance decrement on rotametric and grip-strength tests in rats treated with
      normal saline. In contrast, animals receiving AG either prophylactically before
      or after the blast seemed unaffected by the same blast. This finding also
      correlates well with histologic examination that showed a reduction in
      degenerating cortical neurons in AG-treated rats compared with those receiving
      saline injection. CONCLUSION: It is thus suggested that AG could play a
      neuroprotective role in rats subjected to blast exposure.

PMID- 14960986
TI  - Predicting increased fluid requirements during the resuscitation of thermally
      injured patients.
AB  - BACKGROUND: We determined whether factors present soon after burn predict which
      patients will receive more than 4 mL/kg/% burn during the first 24 hours, and
      whether total fluid intake during the first 24 hours (VOL) contributes to in
      hospital mortality (MORT). METHODS: We reviewed the records of patients admitted
      during 1987-97. The modified Brooke resuscitation formula was used. One hundred
      four patients met inclusion criteria: total body surface area burned (TBSA) > or
      = 20%; admission directly from the field; weight > 30 kg; no electric injury,
      mechanical trauma, or blood transfusions; and survival > or = 24 hours postburn.
      Eighty-nine records were complete. RESULTS: Mean TBSA was 43%, mean full
      thickness burn size was 21%, mean age was 41 years, mean VOL was 4.9 mL/kg/%
      burn, and mean lactated Ringer's volume was 4.4 mL/kg/% burn; 53% had inhalation
      injury. MORT was 25.8%. Mean urine output was 0.77 mL/kg/h. By linear regression,
      VOL was associated with weight (negatively) and full-thickness burn size (r2 =
      0.151). By logistic regression, receipt of over 4 mL/kg/% burn was predicted at
      admission by weight (negatively) and TBSA; by 24 hours postburn, mechanical
      ventilation replaced TBSA. With respect to MORT, logistic regression of admission
      factors yielded a model incorporating TBSA and an age function; by 24 hours
      postburn, the worst base deficit was added. CONCLUSION: Burn size and weight
      (negatively) were associated with greater VOL. However, a close linear
      relationship between burn size and VOL was not observed. Mechanical ventilation
      supplanted TBSA by 24 hours as a predictor of high VOL. Worst base deficit, TBSA,
      and an age function, but not VOL, were predictors of MORT.

PMID- 14960987
TI  - The effect of state motorcycle licensing laws on motorcycle driver mortality
      rates.
AB  - OBJECTIVE: The purpose of this study was to evaluate the association between
      motorcycle licensing and operation regulations and motorcycle mortality rates in
      the United States during 1997 through 1999. METHODS: A population-based ecologic
      study was used. RESULTS: Lower mortality rates were observed in states with the
      following motorcycling requirements: skill test for a motorcycle permit (rate
      ratio [RR], 0.76; 95% confidence interval [CI], 0.69-0.84), driver training (RR,
      0.80; 95% CI, 0.74-0.86), longer duration of learner's permits (95-190 days [RR,
      0.86; 95% CI, 0.79-0.95] and >190 days [RR, 0.87; 95% CI, 0.81-0.93], three or
      more learner's permit restrictions (RR, 0.78; 95% CI, 0.73-0.84), and a full
      helmet law (RR, 0.76; 95% CI, 0.71-0.81). CONCLUSION: Specific motorcycle
      licensure policies appear to be associated with lower mortality rates.

PMID- 14960988
TI  - Unusual seat-belt injuries in children.

PMID- 14960989
TI  - Blunt trauma of the hepatogastric ligament: a case-report.

PMID- 14960990
TI  - Wandering spleen presenting as gastric outlet obstruction after repair of
      traumatic diaphragmatic hernia.

PMID- 14960991
TI  - An unusual cause of a stress femoral fracture in a long-distance runner: a case
      of bilateral fracture.

PMID- 14960992
TI  - Folded free vascularized fibular grafts for the reconstruction of combined
      segmental bone defects of distal tibia and fibula.

PMID- 14960993
TI  - Severe anorectal and vaginal injuries in a jet ski passenger.

PMID- 14960994
TI  - Effects of phosphodiesterase inhibition on the inflammatory response after shock:
      role of pentoxifylline.

PMID- 14960995
TI  - Retrohepatic vena cava and hepatic vein injuries: a simplified experimental
      methods of treatment by balloon shunt.
AB  - BACKGROUND: Fecal contamination from colon injury has been thought to be the most
      significant factor for the development of surgical site infection (SSI) after
      trauma. However, there are increasing data to suggest that other factors may play
      a role in the development of postinjury infection in patients after colon injury.
      The purpose of this study was to determine the impact of gastric wounding on the
      development of SSI and nonsurgical site infection (NSSI) in patients with colon
      injury. METHODS: Post hoc analysis was performed on data prospectively collected
      for 317 patients presenting with penetrating hollow viscus injury. One hundred
      sixty-two patients with colon injury were subdivided into one of three groups:
      patients with isolated colon wounds (C), patients with colon and stomach wounds
      with or without other organ injury (C+S), and patients with colon and other organ
      injury but no stomach injury (C-S) and assessed for the development of SSI and
      NSSI. Infection rates were also determined for patients who sustained isolated
      gastric injury (S) and gastric injury in combination with organ injuries other
      than colon (S-C). Penetrating Abdominal Trauma Index, operative times, and
      transfusion were assessed. Discrete variables were analyzed by Cochran-Mantel
      Haenszel chi2 test and Fisher's exact test. Risk factor analysis was performed by
      multivariate logistic regression. RESULTS: C+S patients had a higher rate of SSI
      infection (31%) than C patients (3.6%) (p = 0.008) and C-S patients (13%) (p =
      0.021). Similarly, the incidence of NSSI was also significantly greater in the
      C+S group (37%) compared with the C patients (7.5%) (p = 0.07) and the C-S
      patients (17%) (p = 0.019). There was no difference in the rate of SSI or NSSI
      between the C and C-S groups (p = 0.3 and p = 0.24, respectively). The rate of
      SSI was significantly greater in the C+S patients when compared with the S-C
      patients (31% vs. 10%, p = 0.008), but there was no statistical difference in the
      rate of NSSI in the C+S group and the S-C group (37% vs. 24%, p = 0.15).
      CONCLUSION: The addition of a gastric injury to a colon injury has a synergistic
      effect on the rate of postoperative infection.

PMID- 14960996
TI  - Missile injury of the head disclosed by computed tomographic scan 60 years later.

PMID- 14960997
TI  - "Endotracheal intubation in the field does not improve outcome in trauma patients
      who present without an acutely lethal traumatic brain injury", by Bochicchio GV,
      et al.

PMID- 14960998
TI  - Use of hemorrhagic shock model based on the endpoints of oxygen debt.

PMID- 14960999
TI  - "Radiographic clearance of blunt cervical spine injury: plain radiograph or
      computed tomography scan?", by Griffen MM, et al.

PMID- 14961000
TI  - "Use of admission Glasgow Coma Score, pupil size, and pupil reactivity to
      determine outcome for trauma patients", by Lieberman JD, et al.

PMID- 14961001
TI  - Outbreaks of avian influenza A (H5N1) in Asia and interim recommendations for
      evaluation and reporting of suspected cases--United States, 2004.
AB  - During December 2003-February 2004, outbreaks of highly pathogenic avian
      influenza A (H5N1) among poultry were reported in Cambodia, China, Indonesia,
      Japan, Laos, South Korea, Thailand, and Vietnam. As of February 9, 2004, a total
      of 23 cases of laboratory-confirmed influenza A (H5N1) virus infections in
      humans, resulting in 18 deaths, had been reported in Thailand and Vietnam. In
      addition, approximately 100 suspected cases in humans are under investigation by
      national health authorities in Thailand and Vietnam. CDC, the World Health
      Organization (WHO), and national health authorities in Asian countries are
      working to assess and monitor the situation, provide epidemiologic and laboratory
      support, and assist with control efforts. This report summarizes information
      about the human infections and avian outbreaks in Asia and provides
      recommendations to guide influenza A (H5N1) surveillance, diagnosis, and testing
      in the United States.

PMID- 14961002
TI  - Cases of influenza A (H5N1)--Thailand, 2004.
AB  - Since mid-December 2003, eight Asian countries (Cambodia, China, Indonesia,
      Japan, Laos, South Korea, Thailand, and Vietnam) have reported an epizootic of
      highly pathogenic avian influenza in poultry and various other birds caused by
      influenza A (H5N1). As of February 9, 2004, a total of 23 laboratory-confirmed
      human cases of influenza A (H5N1) had been reported in Thailand and Vietnam. In
      18 (78%) of these cases, the patients died. Clinical experience with avian H5N1
      disease in humans is limited. The human H5N1 viruses identified in Asia in 2004
      are antigenically and genetically distinguishable from the 1997 and February 2003
      viruses. To aid surveillance and clinical activities, this report provides a
      preliminary clinical description of the initial five confirmed cases in Thailand.

PMID- 14961003
TI  - Secondary and tertiary transfer of vaccinia virus among U.S. military personnel-
      United States and worldwide, 2002-2004.
AB  - In December 2002, the Department of Defense (DoD) began vaccinating military
      personnel as part of the pre-event vaccination program. Because vaccinia virus is
      present on the skin at the site of vaccination, it can spread to other parts of
      the body (i.e., autoinoculation) or to contacts of vaccinees (i.e., contact
      transfer). To prevent autoinoculation and contact transfer, DoD gave vaccinees
      printed information that focused on hand washing, covering the vaccination site,
      and limiting contact with infants (1,2). This report describes cases of contact
      transfer of vaccinia virus among vaccinated military personnel since December
      2002; findings indicate that contact transfer of vaccinia virus is rare.
      Continued efforts are needed to educate vaccinees about the importance of proper
      vaccination-site care in preventing contact transmission, especially in household
      settings.

PMID- 14961004
TI  - Update: adverse events following civilian smallpox vaccination--United States,
      2003.
AB  - During January 24-December 31, 2003, smallpox vaccine was administered to 39,213
      civilian health-care and public health workers in 55 jurisdictions to prepare the
      United States for a possible terrorist attack using smallpox virus. This report
      updates information on vaccine-associated adverse events among civilians
      vaccinated since the beginning of the program and among contacts of vaccinees,
      received by CDC from the Vaccine Adverse Event Reporting System (VAERS) during
      August 9-December 31.

PMID- 14961005
TI  - Global Polio Eradication Initiative Strategic Plan, 2004.
AB  - Since the 1988 World Health Assembly resolution to eradicate poliomyelitis, the
      number of polio-endemic countries has decreased from 125 in 1988 to six in 2003
      (i.e., Afghanistan, Egypt, India, Niger, Nigeria, and Pakistan), and the number
      of cases reported worldwide has decreased from approximately 350,000 to 682. In
      2003, approximately 90% of cases were reported from Nigeria (305), India (220),
      and Pakistan (99); epidemiologic and virologic data demonstrated focal endemic
      transmission in Afghanistan and Niger, with repeated importations from Pakistan
      and Nigeria, respectively, and localized transmission in Egypt. On January 15,
      2004, the World Health Organization (WHO) released an updated Global Polio
      Eradication Initiative Strategic Plan outlining activities required to 1)
      interrupt poliovirus transmission globally, 2) achieve global certification of
      polio eradication, and 3) prepare for global cessation of childhood vaccination
      with oral poliovirus vaccine (OPV). The discontinuation of mass vaccination
      campaigns in the majority of polio-free countries has left these areas vulnerable
      to importations of wild poliovirus (WPV) from the remaining countries in which
      polio is endemic. For polio to be eradicated, all remaining poliovirus reservoirs
      must be eliminated.

PMID- 14961006
TI  - GDNF gene therapy attenuates retinal ischemic injuries in rats.
AB  - PURPOSE: To examine the protective effects of glial cell line-derived
      neurotrophic factor (GDNF) on retinal ischemia-reperfusion injury by using gene
      delivery. METHODS: Gene delivery to retinal cells was achieved through
      intravitreal injections of recombinant adeno-associated virus expressing GDNF
      (rAAV-GDNF) in the right eyes and AAV expressing Escherichia coli LacZ (rAAV
      LacZ) in the left eyes of Sprague-Dawley rats. Ischemic injury was introduced
      three weeks after gene delivery. The synthesis and accumulation of GDNF within
      the retina were determined using immunohistochemistry and enzyme-linked
      immunosorbent assay (ELISA) three weeks after gene delivery. The neuroprotective
      effects of GDNF were evaluated by determining the preservation of the inner
      retina thickness and the cell counts in the retinal ganglion cell (RGC) layer one
      week after reperfusion. In addition, eletroretinograms (ERGs) were performed to
      determine the functionality of the retinas. Finally, the levels of RGC apoptosis
      were measured using the TdT-dUTP terminal nick-end labeling (TUNEL) method 6 h
      after reperfusion. RESULTS: Gene expression of GDNF was demonstrated through
      immunohistochemistry and ELISA. Thinning of the inner retina and decreased
      numbers of cells in RGC layer were noted after ischemia in all of the eyes.
      However, the thickness of the inner retina and the numbers of cells in RGC layer
      were better preserved in rAAV-GDNF treated eyes than in rAAV-LacZ treated eyes
      seven days after reperfusion (p=0.028 and p<0.001, respectively). Also, seven
      days after reperfusion, the rAAV-GDNF treated eyes had retained larger b-wave
      amplitudes than rAAV-LacZ treated eyes (p=0.003). Finally, rAAV-GDNF treated eyes
      had statistically fewer apoptotic cells in the RGC layer than the control eyes
      (p=0.011). CONCLUSIONS: In these experiments, GDNF moderately protected rat
      retina from ischemia-reperfusion injury, possibly by preventing apoptosis in
      retinal cells.

PMID- 14961007
TI  - Comparative study of the three neurofilament subunits within pig and human
      retinal ganglion cells.
AB  - PURPOSE: Neurofilaments (NF) are neuronal cytoskeletal components and
      immunostaining against them has been used to visualize retinal ganglion cells
      (RGC) and their axons. Since the RGC cytoskeleton exhibits differential damage in
      diseases such as glaucoma, we examined the distribution of light, medium, and
      heavy NF subunits (NF-L, NF-M, and NF-H respectively) within normal human and
      porcine retinas, as a function of RGC soma size and eccentricity. METHODS: NF
      subunits were visualized with immunofluorescence techniques using retinal
      sections and flatmounts from adult human and pig retinas that were incubated with
      specific antisera against the three NF subunits. Porcine RGCs were retrogradely
      labeled with fluorogold while human RGCs were identified based on their position
      within the inner retina and their relatively large somata. RESULTS: NF-H and NF-M
      were distributed widely within all RGC somata and dendrites, whereas NF-L was
      more restricted to the perinuclear area. In addition, phosphorylated NF-H
      distribution varied with retinal eccentricity so a subpopulation of large RGCs
      located in the peripheral retina was intensely labeled with the antiserum
      recognizing the phosphorylated NF-H. CONCLUSIONS: We show that at least one of
      each of three NF subunits is present in all RGCs in porcine and presumably in
      human retina, and that NF distribution is very similar in RGCs of both species.

PMID- 14961008
TI  - DNase I and fragmented chromatin during nuclear degradation in adult bovine lens
      fibers.
AB  - PURPOSE: Nuclear loss is a most remarkable organelle disappearance during
      terminal differentiation of lens fiber cells given that it implicates the full
      degradation of a major molecular component, DNA. Consequently, to gain insight
      into the progression of DNA cleavage we analyzed the appearance of single strand
      breaks in relationship with chromatin condensation. To assess a possible
      involvement of DNase I in DNA fragmentation we explored its localization in lens
      fibers having different degrees of nuclear breakdown, evaluated by the state of
      chromatin, nuclear envelope, and DNA. METHODS: Whole mounts of adult bovine lens
      epithelium as well as lens cryosections were utilized to examine, using
      antibodies or specific molecular probes, the localization of DNase I, nuclear
      membrane, lamins, and DNA 3'-OH-free termini. Nuclease activity gel and western
      blot assays were used to characterize DNase I in different lens fiber extracts.
      RESULTS: Nuclear morphology was found to undergo significant changes from the
      onset of fiber differentiation. Initial spherical nuclei present at early
      fibergenesis stages evolve to elongated ones in mature fibers. Chromatin did not
      present signs of condensation in these nuclei. However, nuclei from fibers
      located deeper in lens volume exhibited some chromatin condensation and
      fragmentation while the nuclear lamina appeared undamaged. At more advanced
      stages, different patterns of nuclear envelope integrity and chromatin
      condensation and cleavage were observed. DNase I was found in the cytoplasm in
      the very initial fibers and then in the nuclear territory. DNase I appeared
      closely associated with fully condensed and fragmented chromatin at the final
      phases of nuclear breakdown. CONCLUSIONS: DNase I is a nuclease present in bovine
      lens fibers and can be considered as an enzyme producing final DNA cleavage since
      it is closely associated with highly fragmented DNA in disintegrating nuclei.

PMID- 14961009
TI  - Filling our ranks with experienced professionals.

PMID- 14961010
TI  - The growing population of uninsured: are you prepared for the challenge?

PMID- 14961011
TI  - CAM's struggle for legitimacy.

PMID- 14961012
TI  - Proving disability remains difficult.

PMID- 14961013
TI  - An Internet resource for outcomes support.

PMID- 14961015
TI  - Advocate versus abdicate.

PMID- 14961016
TI  - Clinical documentation improvement: it can make you look good!

PMID- 14961017
TI  - Does your case management career meet your needs?

PMID- 14961019
TI  - Integrating medical and mental health care.

PMID- 14961020
TI  - Chronic pain: the new workers' comp.

PMID- 14961021
TI  - Dear doctor: is there a case manager in the house?

PMID- 14961022
TI  - The foundation for ADA and the rest of the story.

PMID- 14961023
TI  - Negotiating for successful outcomes in case management practice.

PMID- 14961024
TI  - Tension between two kinetochores suffices for their bi-orientation on the mitotic
      spindle.
AB  - The movement of sister chromatids to opposite spindle poles during anaphase
      depends on the prior capture of sister kinetochores by microtubules with opposing
      orientations (amphitelic attachment or bi-orientation). In addition to proteins
      necessary for the kinetochore-microtubule attachment, bi-orientation requires the
      Ipl1 (Aurora B in animal cells) protein kinase and tethering of sister chromatids
      by cohesin. Syntelic attachments, in which sister kinetochores attach to
      microtubules with the same orientation, must be either 'avoided' or 'corrected'.
      Avoidance might be facilitated by the juxtaposition of sister kinetochores such
      that they face in opposite directions; kinetochore geometry is therefore deemed
      important. Error correction, by contrast, is thought to stem from the
      stabilization of kinetochore-spindle pole connections by tension in microtubules,
      kinetochores, or the surrounding chromatin arising from amphitelic but not
      syntelic attachment. The tension model predicts that any type of connection
      between two kinetochores suffices for efficient bi-orientation. Here we show that
      the two kinetochores of engineered, unreplicated dicentric chromosomes in
      Saccharomyces cerevisiae bi-orient efficiently, implying that sister kinetochore
      geometry is dispensable for bi-orientation. We also show that Ipl1 facilitates bi
      orientation by promoting the turnover of kinetochore-spindle pole connections in
      a tension-dependent manner.

PMID- 14961025
TI  - Community structure and metabolism through reconstruction of microbial genomes
      from the environment.
AB  - Microbial communities are vital in the functioning of all ecosystems; however,
      most microorganisms are uncultivated, and their roles in natural systems are
      unclear. Here, using random shotgun sequencing of DNA from a natural acidophilic
      biofilm, we report reconstruction of near-complete genomes of Leptospirillum
      group II and Ferroplasma type II, and partial recovery of three other genomes.
      This was possible because the biofilm was dominated by a small number of species
      populations and the frequency of genomic rearrangements and gene insertions or
      deletions was relatively low. Because each sequence read came from a different
      individual, we could determine that single-nucleotide polymorphisms are the
      predominant form of heterogeneity at the strain level. The Leptospirillum group
      II genome had remarkably few nucleotide polymorphisms, despite the existence of
      low-abundance variants. The Ferroplasma type II genome seems to be a composite
      from three ancestral strains that have undergone homologous recombination to form
      a large population of mosaic genomes. Analysis of the gene complement for each
      organism revealed the pathways for carbon and nitrogen fixation and energy
      generation, and provided insights into survival strategies in an extreme
      environment.

PMID- 14961027
TI  - Imatinib mesylate associated with delayed hematopoietic recovery after
      concomitant chemotherapy.

PMID- 14961028
TI  - p210BCR/ABL-induced alteration of pre-mRNA splicing in primary human CD34+
      hematopoietic progenitor cells.
AB  - Chronic myelogenous leukemia (CML) is a malignancy of the human hematopoietic
      stem cell (HSC) caused by the p210BCR/ABL oncoprotein. Although alternative
      splicing of pre-mRNA is a critical determinant of a cell's protein repertoire, it
      has not been associated with CML pathogenesis. We identified a BCR/ABL-dependent
      increase in expression of multiple genes involved in pre-mRNA splicing (eg SRPK1,
      RNA Helicase II/Gu, and hnRNPA2/B1) by subtractive hybridization of cDNA from
      p210BCR/ABL-eGFP vs eGFP-transduced umbilical cord blood CD34+ cells. beta1
      integrin signaling is important to HSC maintenance and
      proliferation/differentiation, and is abnormal in CML. As an example of how
      changes in pre-mRNA processing might contribute to CML pathogenesis, we observed
      alternative splicing of a gene for a beta1-integrin-responsive nonreceptor
      tyrosine kinase (PYK2), resulting in increased expression of full-length Pyk2 in
      BCR/ABL-containing cells. Treatment of p210BCR/ABL-positive cells with the Abl
      specific tyrosine kinase inhibitor STI571 reverted PYK2 splicing to a
      configuration more consistent with normal cells, and correlated with decreased
      expression of BCR/ABL-induced proteins involved in pre-mRNA processing. Whether
      altered PYK2 splicing contributes to CML pathogenesis remains undetermined;
      however, we propose that generic changes in pre-mRNA splicing as a result of
      p210BCR/ABL kinase activity may contribute to CML pathogenesis.

PMID- 14961029
TI  - Differential stability of control gene and fusion gene transcripts over time may
      hamper accurate quantification of minimal residual disease--a study within the
      Europe Against Cancer Program.

PMID- 14961030
TI  - No evidence for core-binding factor CBFbeta as a leukemia predisposing factor in
      chromosome 16q22-linked familial AML.

PMID- 14961031
TI  - Prophylactic intrathecal chemotherapy in acute promyelocytic leukemia (APL).

PMID- 14961032
TI  - A case of refractory anemia with 17p- syndrome following azathioprine treatment
      for heart transplantation.

PMID- 14961033
TI  - Bcl-6 mutation status provides clinically valuable information in early-stage B
      cell chronic lymphocytic leukemia.
AB  - In B-cell chronic lymphocytic leukemia (B-CLL), somatic mutation of IgVH genes
      defines a subgroup with favorable prognosis, whereas the absence of IgVH
      mutations is correlated with a worse outcome. Mutations of the BCL-6 gene are
      also observed in a subset of B-CLL, but the clinical significance of this
      molecular alteration remains uncertain. We examined the distribution of IgVH and
      BCL-6 gene mutations in 95 well-characterized patients with Binet stage A B-CLL,
      and correlated them with clinical, laboratory, cytogenetic findings and disease
      progression. Mutations of the BCL-6 gene were observed only in cases harboring
      mutated IgVH. Unexpectedly, coexistence of IgVH and BCL-6 mutations was
      correlated with shorter treatment-free interval (TFI) compared to cases harboring
      only IgVH mutation (median, 55 months vs not reached; P=0.01), resembling the
      clinical course of unmutated IgVH cases (median TFI, 44 months). As expected,
      deletions of 17p13 (P53 locus) and 11q22 (ATM locus) were observed in cases with
      unmutated IgVH, except one patient who showed mutations of both IgVH and BCL-6.
      No other statistically significant differences were observed among the genetic
      subgroups. Our data indicate that BCL-6 mutations identify a subgroup of Binet
      stage A B-CLL patients with a high risk of progression despite the presence of
      mutated IgVH gene.

PMID- 14961034
TI  - CD99 expression in T-lineage ALL: implications for flow cytometric detection of
      minimal residual disease.
AB  - Expression of CD99 is higher on immature than on mature T cells. We postulated
      that this marker could be used to assess minimal residual disease (MRD) in T
      lineage acute lymphoblastic leukemia (T-ALL). In diagnostic bone marrow (BM)
      samples from 27 children with T-ALL, expression of CD99 on leukemic lymphoblasts
      by flow cytometry was in median 7.7 times higher than on normal T lymphocytes
      from within the same sample. In 85% of cases, leukemic MFI values were higher
      than the mean MFI+2 s.d. of normal populations. We applied CD99 to study MRD in
      39 follow-up samples from 15 consecutive T-ALL patients, and compared the results
      with those obtained with the well-established MRD-marker terminal
      deoxynucleotidyl transferase (TdT). Either antibody was combined in four-color
      flow cytometry with CD7, surfaceCD3, and cytoplasmicCD3. We found that CD99 was a
      valid complement to TdT in quantifying T-ALL MRD. Given a considerable
      interpatient variability, CD99 could be favorably used in nine patients, and TdT
      in other five patients. Both approaches showed a similar very low nonspecific
      background throughout 12 weeks from diagnosis (in median 0.002% of nucleated BM
      cells in patients with non-T ALL). We conclude that CD99 is a highly informative
      tool for MRD detection in T-ALL, bearing the advantage of surface expression in
      contrast to TdT.

PMID- 14961035
TI  - Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity
      against acute lymphoblastic leukemia.
AB  - To develop a therapy for drug-resistant B-lineage acute lymphoblastic leukemia
      (ALL), we transduced T lymphocytes with anti-CD19 chimeric receptors, consisting
      of an anti-CD19 single-chain variable domain (reactive with most ALL cases), the
      hinge and transmembrane domains of CD8alpha, and the signaling domain of CD3zeta.
      We compared the antileukemic activity mediated by a novel receptor ('anti-CD19-BB
      zeta') containing the signaling domain of 4-1BB (CD137; a crucial molecule for T
      cell antitumor activity) to that of a receptor lacking costimulatory molecules.
      Retroviral transduction produced efficient and durable receptor expression in
      human T cells. Lymphocytes expressing anti-CD19-BB-zeta receptors exerted
      powerful and specific cytotoxicity against ALL cells, which was superior to that
      of lymphocytes with receptors lacking 4-1BB. Anti-CD19-BB-zeta lymphocytes were
      remarkably effective in cocultures with bone marrow mesenchymal cells, and
      against leukemic cells from patients with drug-resistant ALL: as few as 1% anti
      CD19-BB-zeta-transduced T cells eliminated most ALL cells within 5 days. These
      cells also expanded and produced interleukin-2 in response to ALL cells at much
      higher rates than those of lymphocytes expressing equivalent receptors lacking 4
      1BB. We conclude that anti-CD19 chimeric receptors containing 4-1BB are a
      powerful new tool for T-cell therapy of B-lineage ALL and other CD19+ B-lymphoid
      malignancies.

PMID- 14961036
TI  - High expression of activation-induced cytidine deaminase (AID) mRNA is associated
      with unmutated IGVH gene status and unfavourable cytogenetic aberrations in
      patients with chronic lymphocytic leukaemia.
AB  - Activation-induced cytidine deaminase (AID) is essential for somatic
      hypermutation of B-cells. We investigated the expression of AID mRNA by real-time
      polymerase chain reaction (PCR) in peripheral blood mononuclear cells of 80
      patients with B-CLL. AID expression was detected in 45 of 80 patients (56%) at
      various levels, but was undetectable in 35 patients (44%). AID PCR positivity was
      associated with unmutated IGV(H) gene status (22 of 25 patients; P=0.002) and
      unfavourable cytogenetics (18 of 23 patients with deletion in 11q or loss of p53;
      P=0.040). Using a threshold level of 0.01-fold expression compared to Ramos
      control cells, even more significant associations were observed (P=0.001 for
      IGVH; P=0.002 for cytogenetics). A correlation was observed between individual
      AID levels and the percentage of V(H) homology (R=0.41; P=0.001). AID positivity
      predicted unmutated IGV(H) status with an odds ratio of 8.31 (P=0.003) and poor
      risk cytogenetics with an odds ratio of 3.46 (P=0.032). Significance was retained
      after adjustment for Binet or Rai stages. AID mRNA levels were stable over time.
      These data suggest a potential role of AID as a prognostic marker in B-CLL.

PMID- 14961037
TI  - Identification of genes whose expression patterns differ in benign lymphoid
      tissue and follicular, mantle cell, and small lymphocytic lymphoma.
AB  - Improved methods for diagnosing small B-cell lymphomas (SBCLs) and predicting
      patient response to therapy are likely to result from the ongoing discovery of
      molecular markers that better define these malignancies. In this report, we
      identify 120 genes whose expression patterns differed between reactive lymph node
      tissue and three types of SBCL: follicular lymphoma, mantle cell lymphoma, and
      chronic lymphocytic leukemia/small lymphocytic lymphoma. Whereas previously
      published studies have generally analyzed the gene expression profiles of one
      type of SBCL, work presented in this paper was intended to identify genes that
      are differentially expressed between three SBCL subtypes. This analysis was
      performed using mRNA pooled from multiple specimens representing each tissue
      type. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was
      used to validate the differential expression of 23 of these genes. Among the 23
      validated genes were cyclin D1 (CCND1) and B-cell CLL/lymphoma 2, which have well
      known roles in lymphoma pathogenesis. The remaining 21 genes have no currently
      established role in lymphoma development. Using qRT-PCR, the expression of CCND1
      and seven additional genes was further studied in a panel of individual
      specimens. Genes identified in this study are of biological interest and
      represent candidate diagnostic markers.

PMID- 14961038
TI  - Expression of constitutively active Notch4 (Int-3) modulates myeloid
      proliferation and differentiation and promotes expansion of hematopoietic
      progenitors.
AB  - The Notch family of transmembrane receptors has been implicated in the regulation
      of many developmental processes. In this study, we evaluated the role of Notch4
      in immature hematopoietic progenitors by inducing, with retroviral transduction,
      enforced expression of Int-3, the oncogenic and constitutively active form of
      mouse Notch4. Int-3-transduced human myeloid leukemia (HL-60) cells demonstrated
      significantly delayed expression of differentiation markers following retinoic
      acid and 12-0-tetradecanoylphorbol 13-acetate treatment. Furthermore, HL-60 cells
      expressing Int-3 displayed a slower growth rate than cells infected with void
      virus, and accumulation in the G0/G1 phases of cell cycle. Transduction with
      deletion mutants of Int-3 defined the importance of individual domains of the
      protein (in particular, the ANK domain and the C-terminal domain) in the
      inhibition of differentiation and growth arrest of HL-60 cells. When mouse bone
      marrow enriched for stem cells (5-fluorouracil-resistant, lineage negative) was
      transduced and cultured for two weeks, the Int-3-transduced population displayed
      a lower expression of differentiation markers and a three- to five-fold higher
      frequency of colony-forming cells (CFU-GM/BFU-E) than control cultures. These
      results strongly support the notion that Notch signaling inhibits differentiation
      and promotes expansion of hematopoietic stem/progenitor cells.

PMID- 14961039
TI  - Novel technique to facilitate the rapid identification of CLL patients utilising
      the VH3-21 gene.

PMID- 14961040
TI  - Rearranged T-cell receptor beta genes represent powerful targets for
      quantification of minimal residual disease in childhood and adult T-cell acute
      lymphoblastic leukemia.
AB  - Current MRD studies in T-cell acute lymphoblastic leukemia (T-ALL) mainly use T
      cell receptor gamma, delta and SIL-TAL1 gene rearrangements as MRD-PCR targets.
      However, low frequency or limited diversity of these markers restricts the number
      of evaluable patients, particularly because two markers are recommended for MRD
      monitoring. Hence, we developed a new strategy implementing the TCR beta (TCRB)
      locus for MRD quantification. The frequency and characteristics of complete and
      incomplete TCRB rearrangements were investigated in 53 childhood and 100 adult T
      ALL patients using the BIOMED-2 multiplex PCR assay. Clonal rearrangements were
      identified in 92% both childhood and adult T-ALL (Vbeta-Dbeta-Jbeta
      rearrangements in 80%, Dbeta-Jbeta rearrangements in 53%). Comparative sequence
      analysis of 203 TCRB recombinations revealed preferential usage of the 'end
      stage' segment Jbeta2.7 in childhood T-ALL (27%), whereas Jbeta2.3 was most
      frequently involved in adult T-ALL (24%). In complete rearrangements, three
      downstream Vbeta segments (19-1/20-1/21-1) were preferentially used.
      Subsequently, a TCRB real-time quantitative PCR assay to quantify MRD with 13
      germline Jbeta primer/probe combinations and allele-specific oligonucleotides was
      developed and applied to 60 clonal TCRB rearrangements. The assay allowed the
      detection of one leukemic cell within at least 10(4) polyclonal cells in 93% of
      cases and will be of high value for future MRD studies.

PMID- 14961041
TI  - Aggressive natural killer-cell leukemia revisited: large granular lymphocyte
      leukemia of cytotoxic NK cells.
AB  - Aggressive natural killer-cell leukemia (ANKL) is a rare form of large granular
      lymphocyte leukemia, which is characterized by a systemic proliferation of NK
      cells. The clinical features of 22 ANKL cases were analyzed. Hepatomegaly (64%),
      splenomegaly (55%) and lymphadenopathy (41%) were also frequently observed.
      Leukemic cells were identified as CD1-, CD2+, surface CD3-, CD4-, CD5-, CD7+,
      CD8+/-, CD10-, CD11b+/-, CD13-, CD16+, CD19-, CD20-, CD25-, CD33(-), CD34-,
      CD38+, CD56+, CD122+, HLA-DR+ and TCR-. Two of the 16 cases examined for CD57
      were positive and three of the seven cases examined for cytoplasmic CD3. Epstein
      Barr virus was detected in the tumor cells of 11 of the 13 cases examined. No
      common cytogenetic abnormalities were identified and 6q anomaly was detected in
      only one. Three of 13 patients treated with chemotherapy containing
      anthracycline/anthraquinone attained complete remission, in contrast to none of
      the eight who were treated with regimens without anthracycline. Although the
      overall prognosis was poor with a median survival of 58 days, those who attained
      remission showed better prognosis (P=0.005). These findings suggest that ANKL is
      an entity of mature cytotoxic NK-cell neoplasms with distinct phenotype and
      disease presentations. Intensive treatment for ANKL may result in a better
      prognosis.

PMID- 14961042
TI  - Risk of need for extracorporeal membrane oxygenation support in neonates with
      congenital diaphragmatic hernia treated with inhaled nitric oxide.
AB  - BACKGROUND: Congenital diaphragmatic hernia (CDH) is often associated with severe
      pulmonary hypoplasia resulting in hypoxemic respiratory failure unresponsive to
      advanced medical management including the use of inhaled nitric oxide (iNO). For
      these patients, extracorporeal membrane oxygenation (ECMO) serves as the last
      potentially effective treatment choice. Since the efficacy of iNO in this patient
      population is not known and since most neonatal intensive care units using iNO
      for the treatment of these critically ill neonates do not provide ECMO, the
      ability to more accurately predict which patient is at risk for failing medical
      management with iNO and requires a timely transfer to an ECMO center can be life
      saving. Therefore, in this study, we sought to determine the risk factors for the
      need for ECMO in a cohort of 27 neonates with isolated left CDH and hypoxemic
      respiratory failure treated with iNO. STUDY DESIGN: In this retrospective study,
      27 patients with left CDH were identified during a 2-year period. During the
      study period, strict clinical guidelines had been used to standardize iNO
      therapy, to provide adequate lung inflation and cardiovascular support, and to
      recognize treatment failures and the need for ECMO. Logistic regression analysis
      was used to study the relationship between the need for ECMO and a set of
      suspected risk factors. RESULTS: When subjected to logistic regression analysis,
      only the presence of a pneumothorax remained significantly associated with the
      need for ECMO (OR=22; 95% CI=2.18 to 222), while none of the other variables
      examined such as mean airway pressure, FiO2, PaO2, or PaCO2 were predictors for
      the need of ECMO after 6 hours of treatment with iNO. CONCLUSION: These data
      indicate that a prompt transfer to an ECMO center should be initiated for
      hypoxemic patients with CDH receiving medical management with iNO if they develop
      an air leak syndrome.

PMID- 14961043
TI  - AGT and RH blood group polymorphisms affect blood pressure and lipids in Afro
      Caribbeans.
AB  - Population blood pressure variation is most likely due to multiple genes. This is
      likely the reason why monogenic testing with the angiotensinogen (AGT) gene
      polymorphisms on chromosome 1 (1q42-43), especially M235T, has met with negative
      results, especially in those of African descent. The RH blood group system, also
      on chromosome 1 (1 p36.2-34), has likewise been associated with blood pressure
      variation in African-Americans and with the rise in blood pressure with age in
      whites. Using a random sample of the population, we investigated the combined
      effects of single and combined variation of the AGTN M235T and RH genotypes on
      blood pressure, lipids, and lipoprotein concentrations in Afro-Caribbeans aged 18
      60 years from the island nation of Dominica. In monogenic analysis, AGT M235T was
      not associated with blood pressure. However, it was associated with HDL (MM 42+/
      23, MT 44+/-12, TT 52+/-14 (P=0.002)). RH genotype was significantly associated
      with systolic blood pressure (P=0.006) and Apo-A (P=0.003). These effects
      remained after adjustment for age, gender, weight, and BMI. In the polygenetic
      analysis, AGT M235T and RH were significantly associated with systolic blood
      pressure (P=0.037; interaction effects, P=0.068). The association of the AGT
      M235T with blood pressure across RH blood group haplotypes was then tested. Of
      the five RH haplotypes available for analysis, the AGT M235T was significantly
      associated with blood pressure within the "D" haplotype (P=0.01). The RH blood
      group and gender were significantly associated with systolic blood pressure and
      Apo-A levels (P=0.005 and 0.012, respectively). All interactions were independent
      of age and weight. In conclusion, we demonstrate a significant association of AGT
      M235T with blood pressure and cholesterol metabolism in an Afro-Caribbean
      population in the "genetic context" of the RH blood group system. Further
      investigation of these interactions may help understand the effects of genetic
      factors on cardiovascular risk in African-derived and other populations.

PMID- 14961044
TI  - One-year hypertension incidence and its predictors in a working population: the
      IHPAF study.
AB  - THE AIMS OF OUR STUDY WERE: (i). to estimate the yearly incidence rates based on
      one vs two visits in a working population and (ii). to identify incident
      hypertension modifiable risk factors. A total of 21566 normotensive subjects were
      included in a 1-year cohort study. Blood pressure (BP) levels at inclusion and at
      the second year screening were measured on the basis of two visits, that is, if
      BP was over 140/90 mmHg in untreated subjects, they were invited to a control
      visit 1 month later. Height and weight were measured and behavioural risk factors
      were collected. Among the 17465 subjects who completed the entire protocol (9691
      men and 7774 women), 17026 remained normotensive at a 1-year interval and 439
      (325 men and 114 women) became hypertensive. Crude yearly incidence rates based
      on one visit were 6.21% in men and 3.06% in women, compared with 3.04% in men and
      1.34% in women when incidence rates were based on two visits, a more than twofold
      difference. Age and body mass index at baseline were the two major independent
      determinants of incident hypertension in both genders. Smoking and alcohol
      consumption were significant risk factors in men but not in women, and a low
      educational level only in women. BP measurement on separate occasions is
      necessary to avoid overestimation of incidence. Weight in both genders and
      alcohol consumption in men were the main modifiable predictors of hypertension.

PMID- 14961045
TI  - Oxidative stress and baroreflex sensitivity in healthy subjects and patients with
      mild-to-moderate hypertension.
AB  - Decreased baroreflex sensitivity (BRS) is a prognostic marker in essential
      hypertension. Animal experiments suggest that decreased BRS is related to
      increased oxidative stress. Our study was aimed at testing whether oxidative
      stress, estimated by isoprostane 15-F(2t)-IsoP urinary levels, is correlated to
      BRS variation in healthy subjects as well as in patients suffering from essential
      hypertension. Urinary 15-F(2t)-IsoP levels and BRS were evaluated in two groups
      of subjects: healthy volunteers (n=64) and patients with untreated mild-to
      moderate hypertension (n=33). Data were analysed in 61 and 31 subjects,
      respectively, BRS analysis being impossible in three and two subjects,
      respectively. 15-F(2t)-IsoP levels were measured using gas chromatography/mass
      spectrometry. BRS was measured using the sequence method [PS+/RR+ and PS-/RR-]
      and crossspectral analysis (CSP) (MF gain) at rest, lying down. No significant
      correlation was found between basal urinary 15-F(2t)-IsoP levels and BRS
      (sequence method and CSP) in either healthy controls or hypertensive patients.
      Our study shows that oxidative stress is not involved in interindividual
      variations of BRS in healthy subjects and patients suffering from mild-to
      moderate hypertensionJournal of Human Hypertension (2004) 18, 517-521.
      doi:10.1038/sj.jhh.1001684 Published online 12 February 2004

PMID- 14961046
TI  - Awareness and control of hypertension in Austria.

PMID- 14961047
TI  - Prevalence of sexual dysfunctions and correlated conditions in a sample of
      Brazilian women--results of the Brazilian study on sexual behavior (BSSB).
AB  - The objective of this study was to assess the prevalence and risk factors of
      female sexual dysfunctions across a selection of social groups. In all, 1219
      women in the community, aged 18 y or older, answered a 38-question self
      applicable questionnaire. Statistical analysis was performed using multivariate
      logistic regression. The average age was 35.6 y (s.d.=12.31) and the average
      number of sexual intercourses was 2.8 (s.d.=1.94) a week. At least one sexual
      dysfunction was reported by 49% of the women; lack of sexual desire (LSD) by
      26.7%; pain during sexual intercourse (PSI) by 23.1% and orgasmic dysfunction
      (OD) by 21%. Women aged over 40 y represented an LSD and OD risk factor, whereas
      women aged over 25 y showed less likelihood of presenting PSI. The educational
      level was inversely correlated with the risk of LSD, OD and PSI. Depression and
      cardiopathies increased PSI occurrences and women with diabetes mellitus showed a
      higher probability of developing LSD and OD. In conclusion, almost half the women
      had at least one sexual dysfunction, and prevalence increased with age and lower
      educational levels. Preventive medical care for the female population, mainly for
      patients with chronic and/or degenerative diseases, considerably reduced the
      chances of sexual dysfunction.

PMID- 14961048
TI  - Quality of life, mood, and sexual function: a path analytic model of treatment
      effects in men with erectile dysfunction and depressive symptoms.
AB  - Erectile dysfunction (ED) is commonly associated with depressed mood and
      diminished quality of life (QoL), but few studies have investigated the causal
      associations involved. Therefore, we evaluated the correlation between several
      measures of mood, QoL, and sexual function in a retrospective analysis of a
      sample of depressed men (n=152), with ED enrolled in a clinical trial of
      sildenafil citrate (VIAGRA). Strong correlations were observed at baseline among
      measures of erectile function (EF), mood, and overall QoL. Significant treatment
      effects were observed on all three domains, with significant interactions between
      changes in mood and QoL. Based on multiple regression and path analysis, a model
      was developed in which EF changes were associated with improved mood and quality
      of sexual life, which resulted in improved partner satisfaction, family life, and
      overall life satisfaction. These data suggest that QoL changes associated with ED
      therapy may be mediated by changes in sexual function, mood, and family
      relationships.

PMID- 14961049
TI  - Cost implications of sexual dysfunction: the female picture.
AB  - This study examined the clinical workload, outcome and direct costs of managing
      women with sexual dysfunction in an NHS clinic in the UK. A retrospective
      analysis of a 3-month period showed that of 47 referrals to the clinic, 38
      undertook treatment. The therapists' assessments suggested that over 80% of
      patients improved on treatment. The average cost per patient was pound 472
      (compared to pound 335 per annum for erectile dysfunction, which included
      physician's and drug costs). The average cost by type of practitioner was pound
      278 (psychologist), pound 322 (physician), pound 532 (physician and psychologist)
      and pound 597 (sex therapist). Patients required between 1 and 51 treatment
      sessions, which were mainly restricted to psychological therapy. Female sexual
      dysfunction (FSD) represents a significant economic burden to the NHS. Further
      research on the potential role and cost effectiveness of pharmacological agents
      for FSD is warranted.

PMID- 14961050
TI  - Screening for erectile dysfunction as part of periodic examination programs-
      concept and implementation.
AB  - Erectile dysfunction (ED) can be an early and first sign of an underlying
      systemic disease. A screening program is offered by the Israeli Defense Force for
      career servicemen at the staff periodic examination center (SPEC), the aim of
      which was early detection of morbidity. We introduced the Sexual Human Inventory
      for Males (SHIM) questionnaire, in order to detect examinees with ED, and offer
      them suitable treatment options. The purpose of this study is to introduce the
      concept of an ED questionnaire as part of a screening program, and to describe
      the first months of its implementation. A computerized questionnaire is used to
      collect the medical history. The SHIM questionnaire was incorporated into the
      medical questionnaire. Relevant data including compliance to reply, SHIM scores,
      age and accompanying diseases of patients were collected from the computerized
      database of SPEC. A total of 2182 patients reported to SPEC from 1/5/01 to
      1/11/01, 1980 of whom were males. Of the males, 881 (44.5%) chose to fill the
      SHIM questionnaire (mean age 34.5 +/- 6.7 y), and 244 of them (27.7%) had a score
      of 21 or less (20.7% had 17-21, 5.7% 11-16, 1.4% 0-10). The prevalence of ED and
      its severity increases with age. An inverted linear correlation was found between
      age and SHIM score (r = -0.22, P<0.0001). Prevalence of hypertension and diabetes
      mellitus is higher in patients with SHIM score < or =16 compared to those with a
      score > or =22. Only 15% of men with ED refer themselves for medical help. The
      concept of adding an ED questionnaire to a screening program may encourage more
      men to seek treatment, not only for their ED, but also for the underlying
      disease. The platform of a periodic examination offers maximum privacy to the
      examinees, resulting in better cooperation.

PMID- 14961051
TI  - Relevance of methodological design for the interpretation of efficacy of drug
      treatment of premature ejaculation: a systematic review and meta-analysis.
AB  - The aim of this systematic review and meta-analysis is to evaluate whether the
      design and methodology of drug-treatment studies of premature ejaculation affect
      the efficacy outcome differently. Therefore, methodological, design and efficacy
      data from 79 studies (3034 males), published between 1943 and 2003, are reviewed.
      A meta-analysis is performed on 43 selective serotonin reuptake inhibitors
      (SSRIs) and clomipramine studies (1514 males), published between 1973 and 2003;
      these studies were pooled to provide a summary variance-weighted effect size. The
      antidepressant-induced percentage increase of the intravaginal ejaculation
      latency time (IELT) was calculated and examined against various methodological
      items. A significant difference in efficacy between SSRIs was observed. Using
      daily treatment, paroxetine appeared more effective than the other SSRIs.
      Retrospective use of a questionnaire, subjective reports, single-blind and open
      study designs generate far greater variability of ejaculation time both at
      baseline and during active drug treatment than real time assessment by stopwatch.
      In conclusion, at daily treatment, the overall efficacy of paroxetine,
      clomipramine, sertraline and fluoxetine is comparable, but paroxetine exerts the
      strongest ejaculation delay. Only eight (18.5%) studies on antidepressant
      treatment fulfilled all criteria used in evidence-based medicine, for example,
      randomised, double-blind studies with prospective real time (stopwatch)
      assessment of the IELT at each intercourse. Single-blind studies, open designs,
      retrospective reporting, or the use of a questionnaire to assess ejaculation time
      should be avoided.

PMID- 14961052
TI  - Topical application of a Rho-kinase inhibitor in rats causes penile erection.
AB  - Studies from this laboratory have demonstrated that RhoA/Rho-kinase signaling
      mediates vasoconstriction in the penile circulation of the rat and that erection
      results from inhibition of this activity with Y-27632. In prior animal studies, Y
      27632 was administered to the rats by intracavernous injection. To determine if
      topical application of the Rho-kinase inhibitor is an effective mode of delivery,
      Y-27632 was applied to the surface of the tunica albuginea or to the glans penis
      and surrounding skin in intact or castrated rats. Both sites of drug
      administration resulted in a marked increase in the erectile response both with
      and without stimulation of the autonomic innervation of the penile vasculature.
      Although high doses of the drug were found to reduce systemic blood pressure,
      topical administration of the Rho-kinase inhibitor, in appropriate doses, may
      have clinical value for the treatment erectile dysfunction.

PMID- 14961053
TI  - Chromosomal instability is demonstrated by fibroblasts derived from the tunica of
      men with Peyronie's disease.
AB  - Peyronie's disease is a fibrotic disorder, a condition characterized by cellular
      proliferation and excess extracellular matrix production. Previous work in
      related conditions has demonstrated chromosomal instability. This investigation
      was undertaken to analyze fibroblasts derived from Peyronie's disease tunical
      tissue for abnormalities of chromosome number and progression of cytogenetic
      aberrations during cell culture. Tunical tissue was excised from men with
      Peyronie's disease from both plaque and nonplaque tissue and cells were explanted
      in culture. Control cells were derived from both neonatal foreskins and normal
      tunica from men with congenital penile curvature. Fluorescent in situ
      hybridization was used to probe for chromosomes 7, 8, 17, 18, X and Y. Control
      cells demonstrated normal copy number for all chromosomes analyzed. In contrast,
      Peyronie's disease plaque-derived fibroblasts demonstrated frequent aneusomies in
      chromosomes 7, 8, 17, 18 and X and recurrent deletions of chromosome Y.
      Peyronie's disease nonplaque tunica-derived fibroblasts demonstrated infrequent
      chromosomal changes early in culture; however, with repeated passaging the
      majority of cell cultures demonstrated aneusomies in at least one chromosome.
      These data indicate that Peyronie's disease plaque-derived fibroblasts have
      consistent aneusomies even at early passage and that nonplaque tunica-derived
      cells from men with Peyronie's disease also demonstrate chromosomal instability.
      This suggests that the tunica albuginea of men with Peyronie's disease may be
      predisposed to undergoing unregulated fibrosis. These findings confirm the
      transformed nature of the Peyronie's disease tunical fibroblasts studied in this
      analysis. While the etiology of these findings is not clear, it is likely that
      these pathobiological characteristics contribute to the pathophysiology of this
      disease process.

PMID- 14961054
TI  - Role of PKCalpha and PKCiota in phenylephrine-induced contraction of rat corpora
      cavernosa.
AB  - Constriction of the penile vasculature prevents erection and is largely mediated
      by physiological agonists. We hypothesized that protein kinase C (PKC) may act as
      a regulator of penile vascular tone. Studies were designed to identify PKC
      isoforms present and to investigate their roles in phenylephrine-induced muscle
      contraction in the isolated rat corpora cavernosa. We demonstrated the presence
      of PKCalpha, beta, gamma, epsilon, delta, eta, and iota in rat corpora cavernosa
      and a subcellular distribution, which favored a membrane association for
      PKCalpha, beta, delta, and iota. Phenylephrine (3 microM) generated an active
      stress of 9.6 +/- 1.5 mN/mm2 and was associated with a significant increase of
      PKCalpha and PKCiota immunoreactivity in the particulate fraction. The amount of
      PKCalpha and PKCiota in the particulate fraction rose by 36 +/- 4.4 and 51 +/-
      2.2% with phenylephrine stimulation. Furthermore, the phenylephrine concentration
      response curve was potentiated in the presence of phorbol 12-myristate13-acetate
      (PMA) (0.1 microM), a PKC activator (EC50: phenylephrine 1.0 +/- 0.8 microM vs
      phenylephrine + PMA 0.3 +/- 0.1 microM) and inhibited in the presence of
      chelerythrine chloride (30 microM), a PKC inhibitor (EC50: phenylephrine 1.0 +/-
      0.8 microM vs phenylephrine + chelerythrine chloride 5.7 +/- 2.4 microM). Based
      on these results, we suggest a potential role for PKCalpha and PKCiota in
      phenylephrine-induced smooth muscle tone of the rat cavernosum.

PMID- 14961055
TI  - Possible hemodynamic pathways of intraurethral prostaglandin-E1 (MUSE).
AB  - Intraurethral application of prostaglandin-E1 (MUSE) is a well-tolerated
      pharmacotherapy for erectile dysfunction. However, the physiological mechanisms
      of drug transfer into the cavernous bodies are not completely clear. Using
      spongiosography in 35 patients, our study tried to elucidate existing shunt
      mechanisms. The X-rays show venous drainage through the deep dorsal vein up to
      the plexus Santorini. The circumflex veins are also contrasted and the cavernous
      bodies show opacification in their distal portion only. Structures shunting
      directly between the corpus spongiosum and the cavernous bodies were not
      demonstrable. Retrograde filling of the cavernous bodies through the deep dorsal
      vein and its circumflex braches seems to be the most relevant way of drug
      transfer after intraurethral application of prostaglandin-E1. Diffusion into the
      cavernous bodies or a systemic mechanism of action does not seem probable.

PMID- 14961056
TI  - Functional evidence for nitrergic neurotransmission in a human clitoral corpus
      cavernosum: a case study.
AB  - Although the presence of neuronal nitric oxide synthase (nNOS) has been
      demonstrated in human clitoral corpus cavernosum, functional evidence for the
      nitrergic neurotransmission as a nonadrenergic noncholinergic (NANC) transmitter
      has been limited to animal studies. Here we show that electrical field
      stimulation elicited reproducible NANC relaxation responses in a clitoral corpus
      cavernosum, obtained from a 38-y-old woman undergoing clitoral reduction surgery.
      These relaxation responses were abolished by an inhibitor of NO synthase or
      tetrodotoxin proving that they were nitrergic in nature and neuronal in origin.
      Large and small calibre nitrergic nerves were demonstrated with
      immunohistochemistry using nNOS antibody, which were also immunostained with
      cholinergic nerve markers. nNOS expression was confirmed using Western blotting.
      This is the first report to show that NO produced by nNOS within the cholinergic
      nitrergic nerves is responsible for the NANC relaxation responses in a human
      clitoral corpus cavernosum.

PMID- 14961057
TI  - Predicting responsiveness to the treatment of rapid ejaculation with 25 mg
      clomipramine as needed.
AB  - Clomipramine (25 mg) taken as needed increases ejaculatory latency in men with
      rapid ejaculation (RE), although only about half the men treated respond to this
      regimen. It would therefore be clinically advantageous to know the patient's
      potential responsiveness to an 'as needed' regimen prior to treatment. The
      present study attempted to identify a priori factors that might enable prediction
      of patients' response or nonresponse to 'as needed' clomipramine. Variables
      relevant to rapid ejaculation were examined in 23 men with RE, 12 of whom had
      responded to clomipramine. Logistic regression indicated that three factors
      assessed prior to treatment--initial ejaculation latency, overall sexual
      satisfaction, and ejaculation frequency each week--significantly improved the
      prediction of responsiveness to this treatment regimen. Specifically, RE men with
      initial ejaculatory latencies over 60 s, self-reported sexual satisfaction of 5
      or higher (on a seven-point scale), and ejaculation frequency of twice or more
      weekly were more likely to benefit from 25 mg 'as needed' clomipramine. As such,
      men meeting these criteria might be considered for this treatment regimen. Those
      not matching these characteristics might better be considered for 20 or 30 mg
      clomipramine given on a daily basis.

PMID- 14961058
TI  - Influence of erectile dysfunction on health related quality of life of male
      kidney transplant patients.
AB  - The objective of the present study was to investigate if a psychological
      adaptation capacity exists in kidney transplant bearers, even with ageing, in
      relation to erectile dysfunction (ED). We studied ED using IIEF-5 and health
      related quality of life (HRQoL) using the SF-36 Health Survey, in a large sample
      of male renal transplant patients (n=242), searching for the influence of ED on
      HRQoL. Patients included 199 patients (82%); the median age was 52 y (43-62); 106
      patients (54.9%) presented ED. These patients were divided into four groups
      according to median age. SF-36 scores were worse for ED vs non-ED patients in the
      first three age groups, but not in age group 4. SF-36 Mental Component Summary
      was similar for patients with ED and without ED in all age groups. We confirm the
      hypothesis that a psychological adaptation occurs in renal transplant patients in
      all age groups, when suffering ED.

PMID- 14961059
TI  - Psycho-biological correlates of hypoactive sexual desire in patients with
      erectile dysfunction.
AB  - We studied the psychological and biological correlates of hypoactive sexual
      desire (HSD) in a consecutive series of 428 patients with erectile dysfunction
      (ED), by using the structured interview SIEDY. A complete physical examination
      and a series of biochemical, hormonal, psychometric, and penile vascular tests
      were also performed. Among the patients studied, 22.8% reported a mild, 12.9% a
      moderate, and 4.6% a complete loss of sexual interest. Patients reporting HSD
      showed significantly lower testosterone (T) levels than the rest of the sample,
      although the prevalence of hypogonadism (T<10 nM) was comparable in the two
      groups. Only a minority (<2%) had severe hyperprolactinemia (>700 mU/l), which,
      nonetheless, was closely associated with a relevant HSD. Both mental disorders
      and use of medication interfering with sexual function were significantly
      associated with HSD, as well as depressive and anxiety symptoms. HSD patients
      showed significantly higher scores in SIEDY scale 2, which explores the
      relational component of ED. In particular, perceived partner's libido and climax
      were crucially associated with an impairment of patients' sexual desire. In
      conclusion, HSD in ED is associated with several biological, psychological, and
      relational factors that can be simultaneously identified and quantified using the
      SIEDY structured interview.

PMID- 14961060
TI  - NCX-911, a novel nitric oxide-releasing PDE5 inhibitor relaxes rabbit corpus
      cavernosum in the absence of endogenous nitric oxide.
AB  - Phosphodiesterase type 5 (PDE5) inhibitors have reduced efficacy in treating
      erectile dysfunction (ED) in conditions where there is a lack of endogenous
      nitric oxide (NO). Therefore, NO-releasing PDE5 inhibitors have been developed.
      Here we report the effect of such a compound, NCX-911, on the tone and nitrergic
      relaxations of rabbit corpus cavernosum in the absence or presence of a NO
      synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME; 500 microM). NCX
      911 was found to be as potent as sildenafil at inducing relaxation of rabbit
      cavernosum (EC(50) values 997.8+/-195.7 and 1000.5+/-140.8 nM, respectively). The
      potency of NCX-911 was not altered, but that of sildenafil decreased five-fold in
      the presence of L-NAME (EC(50) values 1281.2+/-268.3 and 4959.1+/-882.1, nM
      respectively, P<0.001 for sildenafil). Both compounds potentiated nitrergic
      relaxations with similar potencies. These results suggest that NO-releasing PDE5
      inhibitors could potentially be more useful than PDE5 inhibitors in the treatment
      of ED in conditions where there is a lack of endogenous NO.

PMID- 14961061
TI  - Sexual response in men with inhibited or retarded ejaculation.
AB  - Inhibited ejaculation (IE) is a poorly understood male sexual dysfunction having
      both somatic and psychological etiologies. This study investigated sexual
      response in 25 IE men with no probable somatic cause. Using a standard
      psychophysiological assessment procedure, these men were compared with sexually
      functional and other dysfunctional groups on two measures of sexual response:
      erectile response and self-reported sexual arousal. Within the sample of IE men,
      sexual response was investigated as a function of both diagnostic classification
      and relationship factors. Differences occurred between IE men and the other
      groups on erectile response and self-reported sexual arousal during psychosexual
      stimulation in the lab, with IE men reporting lowest levels of sexual arousal.
      Within the IE group, diagnostic classifications and relationship variables were
      also related to self-reported sexual arousal. These findings suggest that
      inhibited arousal may be fairly common among IE men having no apparent somatic
      etiology, and further that several specific relationship factors may provide
      potential strategies for enhancing arousal in these men.

PMID- 14961062
TI  - Erectile dysfunction in primary care: prevalence and patient characteristics. The
      ENIGMA study.
AB  - The availability of adequate treatment for erectile dysfunction (ED) triggers
      studies into the prevalence of ED in the general population. Yet, previous
      studies showed different prevalence estimates partly due to differences in
      patient selection, in (unclear) definitions of ED and in assessment. ENIGMA has
      been designed to study the prevalence of ED in the general population of The
      Netherlands, using the WHO definition with a description of the way of
      assessment. In all, 5721 mail surveys were sent to all men, aged 18 y and older
      in 12 general practices in The Netherlands. A total of 5601 were included in the
      study and 2117 (38%) were completed. A total of 38% of the men reported to have
      ever had some kind of erectile problem. The prevalence of ED was 17% (6% mild, 4%
      moderate and 7% complete). Age, diabetes, cardiovascular diseases, penile
      disorders, irradiation in the pelvic region, relational problems, fear for
      failure, surmenage, medication use and regular consumption of alcohol were
      independently related to ED. Men with ED were less content with their (sexual)
      life and had less confidence in sexual performance. Presence of ED was negatively
      related to affected happiness in life. ED is commonly found in men and is related
      to age, medication, comorbidity and lifestyle factors. Men with ED perceive a
      lower quality of (sex)life. Doctors should be aware of the presence of ED and its
      consequences in patients.

PMID- 14961063
TI  - The value of penile duplex in the prediction of intracavernous drug-induced
      priapism.
AB  - The aim of this work is to assess the value of penile duplex in the prediction of
      intracavernous drug-induced ischemic priapism. A total of 400 patients with
      erectile dysfunction were evaluated before and after diagnostic intracavernous
      injection of a trimix solution (papaverine+phentolamine+PGE1) using color Doppler
      sonography. In all, 29 patients experienced sustained rigid erections for more
      than an hour. Patients were further divided into two groups. Group A included
      patients with spontaneous resolution of their rigid erection within 3 h (10/29)
      and group B included patients with priapism (19/29) that did not resolve within 3
      h. In group A, patients had minimal cavernous artery blood flow within the first
      hour postinjection, that increased with relief of their erection. Group B
      patients had no blood flow in their cavernous artery an hour after intracavernous
      injection and for 6 h later. The disappearance of blood flow in the cavernous
      artery after an hour of sustained rigid erection predicted priapism with 100%
      specificity and sensitivity. The persistent absence of cavernous artery blood
      flow for more than an hour, as detected by color Doppler ultrasound, is an
      objective predictor of priapism. This may guide early intervention to resolve the
      prolonged erection.

PMID- 14961064
TI  - Satisfaction with the malleable penile prosthesis among couples from the Middle
      East--is it different from that reported elsewhere?
AB  - No studies from the Middle East have investigated the psychosexual aspects of
      penile prosthesis. Therefore, several questions were used herein to address
      satisfaction with the use of malleable penile prosthesis among couples from this
      geographic area, as an option to treat erectile dysfunction (ED). A total of 50
      patients who underwent the insertion of AMS 650 and Acu-form penile prostheses
      and their partners were evaluated with a retrospective clinical record review, as
      well as patient and partner questionnaires. In all, 70% of the patients and 57%
      of the partners were satisfied with the prosthesis. There was an increase in
      frequency of intercourse, sexual desire, and ability to achieve orgasm. Dislike
      for the device was the most common cause for nonsatisfaction of patients with the
      device, while sense of unnaturalness was that for partners. Results from this
      evaluation highlight the obvious need for proper preoperative counseling for both
      the patient and his partner to minimize unrealistic expectations. They also
      emphasize the importance of careful screening of both psychosocial and
      psychosexual aspects of the couple based on cultural ethnic background, since
      these are important predictors of the therapeutic outcome of prosthesis
      insertion. Efforts to extend information about ED to the public may be useful to
      reduce patients' exaggerated embarrassment about this problem and make their
      partners actively involved in the treatment.

PMID- 14961065
TI  - Picolinic acid- or desferrioxamine-inducible autocrine activation of macrophages
      engineered to produce IFNgamma: an approach for gene therapy.
AB  - Macrophage (Mphi)-based vectors are highly mobile cellular shuttles designed to
      deliver therapeutic genes within the tissues. We engineered a mouse Mphi cell
      line to express the murine interferon-gamma (IFNgamma) under the control of an
      inducible promoter containing the hypoxia-responsive element, which can be
      triggered by hypoxia and other stimuli. We show that this Mphi vector can be
      induced to produce IFNgamma under normoxic conditions by stimulation with
      picolinic acid (PA), a catabolite of tryptophan, or desferrioxamine (DFX), an
      iron-chelating drug. The Mphi vector responds to IFNgamma with the induction of
      IRF-1 and of other IFNgamma-inducible genes, the expression of Ia antigens and
      induction of phagocytic activity. Inducible nitric oxygen synthase gene
      expression, nitric oxide production, as well as TNFalpha secretion were enhanced
      by PA or DFX as the sole stimuli. None of the above responses could be triggered
      individually by PA or DFX in control, normal Mphi, indicating that the Mphi
      vector overcame the need for costimulatory molecules derived from the immune
      system for its full activation. Furthermore, we demonstrate that extracellular
      iron can downregulate such response, thereby identifying an additional tool for
      the fine tuning of the Mphi vector response to stimulation.

PMID- 14961066
TI  - Adeno-associated viral glutamate decarboxylase expression in the lateral nucleus
      of the rat hypothalamus reduces feeding behavior.
AB  - In vivo gene transfer of glutamate decarboxylase (GAD) has been explored as a
      means of inducing or increasing the production of the inhibitory amino-acid
      neurotransmitter, GABA. This strategy has been applied to neuroprotection,
      seizure prevention, and neuromodulation. In the present experiment, AAV2 was used
      to transfer the genes for green fluorescence protein (GFP) and GAD65 into the
      lateral nucleus of the rat hypothalamus. Microinjection of 500 nl of AAV2
      resulted in transduction of a 0.25+/-0.04 mm(3) with targeting errors of X=0.48
      mm, Y=0.18 mm, Z=0.37 mm using standard stereotactic technique. Pre- and
      postinjection food and water consumption, urine and feces production, and weight
      were recorded. In comparison with rAAVCAGGFP- and PBS-injected animals, rats
      treated with rAAVCAGGAD65 demonstrated reduced weight gain (P<0.014) and
      transiently reduced daily food consumption (P<0.007) during the postoperative
      period. No changes in water consumption or waste production were recorded.
      Effective GAD65 gene transfer was confirmed with in situ hybridization using a
      probe to the woodchuck post-transcriptional regulatory element sequence included
      in the vector. These findings suggest that increased GABA production in lateral
      nucleus of the hypothalamus induced by GAD65 gene transfer may reduce weight gain
      through reduced feeding.

PMID- 14961067
TI  - Postischemic administration of Sendai virus vector carrying neurotrophic factor
      genes prevents delayed neuronal death in gerbils.
AB  - Sendai virus (SeV) vector-mediated gene delivery of glial cell line-derived
      neurotrophic factor (GDNF) and nerve growth factor (NGF) prevented the delayed
      neuronal death induced by transient global ischemia in gerbils, even when the
      vector was administered several hours after ischemia. Intraventricular
      administration of SeV vector directed high-level expression of the vector-encoded
      neurotrophic factor genes, which are potent candidates for the treatment of
      neurodegenerative diseases. After occlusion of the bilateral carotid arteries of
      gerbils, SeV vector carrying GDNF (SeV/GDNF), NGF (SeV/NGF), brain-derived
      neurotrophic factor (SeV/BDNF), insulin-like growth factor-1 (SeV/IGF-1) or
      vascular endothelial growth factor (SeV/VEGF) was injected into the lateral
      ventricle. Administration of SeV/GDNF, SeV/NGF or SeV/BDNF 30 min after the
      ischemic insult effectively prevented the delayed neuronal death of the
      hippocampal CA1 pyramidal neurons. Furthermore, the administration of SeV/GDNF or
      SeV/NGF as late as 4 or 6 h after the ischemic insult also prevented the death of
      these neurons. These results indicate that SeV vector-mediated gene transfer of
      neurotrophic factors has high therapeutic potency for preventing the delayed
      neuronal death induced by transient global ischemia, and provides an approach for
      gene therapy of stroke.

PMID- 14961068
TI  - Targeted conversion of the transthyretin gene in vitro and in vivo.
AB  - Familial amyloidotic polyneuropathy (FAP) is the common form of hereditary
      generalized amyloidosis and is characterized by the accumulation of amyloid
      fibrils in the peripheral nerves and other organs. Liver transplantation has been
      utilized as a therapy for FAP, because the variant transthyretin (TTR) is
      predominantly synthesized by the liver, but this therapy is associated with
      several problems. Thus, we need to develop a new treatment that prevents the
      production of the variant TTR in the liver. In this study, we used HepG2 cells to
      show in vitro conversion of the TTR gene by single-stranded oligonucleotides
      (SSOs), embedded in atelocollagen, designed to promote endogenous repair of
      genomic DNA. For the in vivo portion of the study, we used liver from transgenic
      mice whose intrinsic wild-type TTR gene was replaced by the murine TTR Val30Met
      gene. The level of gene conversion was determined by real-time RCR combined with
      mutant-allele-specific amplification. Our results indicated that the level of
      gene conversion was approximately 11 and 9% of the total TTR gene in HepG2 cells
      and liver from transgenic mice, respectively. Gene therapy via this method may
      therefore be a promising alternative to liver transplantation for treatment of
      FAP.

PMID- 14961069
TI  - Liposomal gene transfer of multiple genes is more effective than gene transfer of
      a single gene.
AB  - Liposomal gene transfer is an effective therapeutic approach for the treatment of
      several pathophysiologic states. The purpose of the present study was to define
      whether gene transfer of multiple genes is a feasible approach and whether this
      approach would be more effective than the single transfer of cDNA. Rats were
      inflicted an acute wound and divided into four groups to receive weekly
      subcutaneous injections of liposomes plus the Lac-Z gene (0.22 microg, vehicle),
      or liposomes plus the insulin like-growth factor-I (IGF-I)cDNA (2.2 microg) and
      Lac Z gene (0.22 microg), or liposomes plus the keratinocyte growth factor (KGF)
      cDNA (2.2 microg) and Lac Z gene (0.22 microg), or liposomes plus the IGF-I/KGF
      cDNA (2.2 microg) and Lac Z gene (0.22 microg). Planimetry, immunological assays,
      histological and immunohistochemical techniques were used to determine molecular
      mechanisms after gene transfer, protein expression, dermal and epidermal
      regeneration. IGF-I/KGF cDNA transfer increased IGF-I and KGF protein
      concentration and caused concomitant cellular responses, for example,by
      increasing IGFBP-3, P<0.05. IGF-I/KGF cDNA gene transfer improved epidermal
      regeneration by exhibiting the most rapid area and linear wound re-epithelization
      by almost 250% compared to control and each growth factor given individually,
      P<0.001, which was probably due to promitogenic and antiapoptotic effects on
      basal keratinocytes when compared to controls, P<0.001. Dermal regeneration was
      improved in IGF-I/KGF cDNA-treated animals by an increased collagen deposition
      and morphology when compared with vehicle, IGF-I and KGF, P<0.001. IGF-I/KGF cDNA
      increased VEGF concentrations and thus neovascularization when compared with
      vehicle, IGF-I and KGF, P<0.001. In the present study, we showed that exogenous
      gene transfer of multiple cDNA sequences have an additive effect on intracellular
      and biological responses when compared to the same gene administered as a single
      cDNA sequence. Our findings demonstrate that gene therapy with multiple genes is
      feasible, and that the gene transfer of multiple genes can enhance and accelerate
      physiologic and biological effects.

PMID- 14961070
TI  - T-cell response to adenovirus hexon and DNA-binding protein in mice.
AB  - The successful development of adenovirus vectors for vaccines and gene therapy
      will require a better understanding of the host immune response. Using the
      ELISPOT assay to measure IFN-gamma-secreting CD8(+) cells, we identify
      immunodominant epitopes of the adenovirus hexon and DNA-binding protein in BALB/c
      and C57BL/6 mice. The T-cell response to the intramuscular administration of
      adenovirus serotype 5 peaks within a few weeks and gradually declines but is
      still detectable after 12 weeks. A second administration did not substantially
      increase the number of reactive T cells. The CD8(+) T-cell response was also
      similar between wild type and E1-deleted adenovirus. When B-cell-deficient mice
      were injected with adenovirus encoding the gene for secreted alkaline
      phosphatase, sera phosphatase activity was reduced more quickly in mice pre
      exposed to adenovirus. These results add to the evidence that cell-mediated
      immunity is a substantial barrier to therapeutic adenoviral vectors and provide
      more quantitative tools to measure cellular immune responses to adenovirus.

PMID- 14961071
TI  - Combination of a new generation of PNAs with a peptide-based carrier enables
      efficient targeting of cell cycle progression.
AB  - The design of potent systems for the delivery of charged and noncharged molecules
      that target genes of interest remains a challenge. We describe a novel technology
      that combines a new generation of peptide nucleic acids (PNAs), or HypNA-pPNAs,
      with a new noncovalent peptide-based delivery system, Pep-2, which promotes
      efficient delivery of PNAs into several cell lines. We have validated the
      potential of this technology by showing that Pep2-mediated delivery of an
      antisense HypNA-pPNA chimera directed specifically against cyclin B1 induces
      rapid and robust downregulation of its protein levels and efficiently blocks cell
      cycle progression of several cell lines, as well as proliferation of cells
      derived from a breast cancer. Pep-2-based delivery system was shown to be 100
      fold more efficient in delivering HypNA-pPNAs than classical cationic lipid-based
      methods. Whereas Pep-2 is essential for improving the bioavailability of PNAs and
      HypNA-pPNAs, the latter contribute significantly to the efficiency and
      specificity of the biological response. We have found that Pep-2/HypNA-pPNA
      strategy promotes potent antisense effects, which are approximately 25-fold
      greater than with classical antisense oligonucleotide directed specifically
      against the same cyclin B1 target. Taken together, these data demonstrate that
      peptide-mediated delivery of HypNA-pPNAs constitutes a very promising technology
      for therapeutic applications.

PMID- 14961072
TI  - Transcription factor decoy for AP-1 reduces mesangial cell proliferation and
      extracellular matrix production in vitro and in vivo.
AB  - Diabetic nephropathy is characterized by an expansion of glomerular mesangium,
      caused by mesangial cell proliferation and excessive accumulation of
      extracellular matrix (ECM) proteins, which eventually leads to glomerulosclerosis
      and renal failure. Activator protein-1 (AP-1), a transcription factor, is
      implicated in the transcriptional regulation of a wide range of genes
      participating in cell proliferation and ECM production. This investigation was
      undertaken to test the hypothesis that AP-1 plays an important role in ECM gene
      expression, and to develop a molecular therapeutic strategy based on decoy
      oligodeoxynucleotides (ODN). In this report, we show that transfection with AP-1
      decoy ODN strongly inhibits high glucose- and angiotensin II-induced cell
      proliferation and expression of ECM genes in cultured mesangial cells in vitro.
      Administration of AP-1 decoy ODN into streptozotocin-induced diabetic rat kidney
      in vivo using the hemagglutinating virus of Japan (HVJ)-liposome method virtually
      abolished TGF-beta1 and plasminogen activator inhibitor-1 expression. Our results
      collectively indicate that AP-1 activation is crucial for mesangial cell
      proliferation and ECM production in response to high glucose and angiotensin II.
      Moreover, use of stable AP-1 decoy ODN combined with the highly effective HVJ
      liposome method provides a novel potential molecular therapeutic strategy for the
      prevention of diabetic nephropathy.

PMID- 14961073
TI  - Polymorphic variation in the CBLB gene in human type 1 diabetes.
AB  - CBLB was evaluated as a candidate gene for type 1 diabetes (T1D) susceptibility
      based on its association with autoimmunity in animal models and its role in T
      cell costimulatory signaling. Cblb is one of the two major diabetes predisposing
      loci in the Komeda diabetes-prone (KDP) rat. Cbl-b, a ubiquitin ligase, couples
      TCR-mediated stimulation with the requirement for CD28 costimulation, regulating
      T-cell activation. To identify variants with possible effects on gene function as
      well as haplotype tagging polymorphisms, the human CBLB coding region was
      sequenced in 16 individuals with T1D: no variants predicted to change the amino
      acid sequence were identified. Seven single-nucleotide polymorphism (SNP) markers
      spanning the CBLB gene were genotyped in multiplex T1D families and assessed for
      disease association by transmission disequilibrium testing. No significant
      evidence of association was obtained for either individual markers or marker
      haplotypes.

PMID- 14961074
TI  - Alpha-catenin is required for IGF-I-induced cellular migration but not invasion
      in human colonic cancer cells.
AB  - The mechanisms by which growth factors cooperate with cell adhesion molecules to
      modulate epithelial cell motility remain poorly understood. Here, we investigated
      the role of the E-cadherin/catenin complex in insulin-like growth factor (IGF-I)
      dependent cell migration and invasion. We used variants of the HCT-8 colon cancer
      family that differ in their expression of alphaE-catenin, an intracellular
      molecule that links the E-cadherin/catenin complex to the actin cytoskeleton.
      Migration was determined using a monolayer wound model and cell invasion by the
      penetration of the cells into type-I collagen gels. We showed that alpha-catenin
      deficient cells were not able to migrate in cohort upon IGF-I stimulation.
      Transfection of these cells with alpha-catenin isoforms (alphaN- or alphaT
      catenin) restored migratory response IGF-I. These results suggest that alpha
      catenins are involved in the signal issued from the E-cadherin/catenin complex to
      regulate IGF-I-stimulated migration. In contrast, IGF-I promoted invasion of both
      alpha-catenin-deficient and alpha-catenin-expressing cells, indicating that alpha
      catenin did not participate in the regulation of IGF-I-induced invasion.
      Inhibition of E-cadherin function by treatment with MB-2 monoclonal antibodies
      inhibited both IGF-I-dependent cell migration and invasion. Taken together, our
      results indicate that functional alpha-catenin is essential for migration but not
      for invasion, while E-cadherin is involved in both phenomena.

PMID- 14961075
TI  - Expression of activated M-Ras in a murine mammary epithelial cell line induces
      epithelial-mesenchymal transition and tumorigenesis.
AB  - The expression of activated mutants of M-Ras (G22V or Q71L), but not wild-type M
      Ras, in a murine mammary epithelial cell line, scp2, resulted in epithelial
      mesenchymal transition (EMT) and oncogenic transformation. Cells expressing
      constitutively active M-Ras continued to grow in the absence of serum and
      exhibited a loss of the epithelial markers cytokeratin, E-cadherin and beta
      catenin, together with a gain of the mesenchymal marker vimentin, a loss of
      contact inhibition in monolayer growth and a gain of the capacity for anchorage
      independent growth. Moreover, unlike the parental cells, they failed to form
      differentiated mammospheres on Matrigel and instead formed branched networks of
      cells that grew and invaded the Matrigel. The expression of activated p21 Ras
      (G12V H-Ras or Q61K N-Ras) also resulted in EMT and tumorigenesis, although there
      was evidence that expression of higher levels was toxic. Tumors derived from scp2
      cells expressing activated M-Ras exhibited activation of Akt and of ERK. The
      levels of expression of Q71L M-Ras and G12V H-Ras required for tumorigenesis were
      comparable, although higher levels of the weaker G22V M-Ras mutant were selected
      for in vivo. These data indicate that the expression of activated mutants of M
      Ras was sufficient for oncogenic transformation of a murine mammary epithelial
      cell line.

PMID- 14961076
TI  - Discreet mutations from c-Rel to v-Rel alter kappaB DNA recognition, IkappaBalpha
      binding, and dimerization: implications for v-Rel oncogenicity.
AB  - The avian Rev-T retrovirus encodes the oncoprotein v-Rel, a member of the
      Rel/nuclear factor (NF)-kappaB transcription factor family. The aggressive
      oncogenic potential of v-Rel has arisen from multiple mutations within the coding
      sequence of the avian cellular protein c-Rel. In this study, using quantitative
      biochemical experiments, we have tested the role of a limited set of alterations
      between v-Rel and c-Rel located within the Rel homology region (RHR) of the
      family that might confer functional differences. Our results show that only a set
      of six mutations within the RHR of v-Rel are responsible for its ability to bind
      to a broad spectrum of kappaB-DNA that are normally regulated by distinct NF
      kappaB dimers. We also observe that both v-Rel homodimer and p50/v-Rel
      heterodimer bind IkappaBalpha weakly compared to other cellular Rel/NF-kappaB
      dimers with transcription activation potential. We suggest that the ability of v
      Rel homodimer to deregulate subunit-specific gene expression and its ability to
      evade IkappaB inhibition are crucial to its strong oncogenic potential.

PMID- 14961077
TI  - p53 disruption profoundly alters the response of human glioblastoma cells to DNA
      topoisomerase I inhibition.
AB  - A critical challenge in cancer research is to identify genetic lesions that
      sensitize patients to chemotherapy. p53, which is mutated in nearly one-third to
      half of glioblastomas, may be such a lesion. In this paper, we demonstrate that
      p53 disruption dramatically sensitizes glioblastoma cells to DNA topoisomerase I
      inhibitor-mediated apoptosis. Using 19 glioblastoma cell lines, including 15 low
      passage ex vivo cell lines derived from patients, as well as isogenic
      glioblastoma cells varying in p53 status, we show that clinically relevant levels
      of SN-38 potently induce cell cycle arrest and temporary senescence in
      glioblastoma cells with wild-type p53 while causing massive apoptosis in p53
      deficient cells (P<0.0002). We demonstrate that glioblastoma cells with wild-type
      p53 proliferate when recultured in drug-free medium, whereas p53-deficient cells
      do not. We also show that p16 protein expression is neither necessary nor
      sufficient for initiation and/or maintenance of SN-38-induced arrest/senescence.
      These results indicate that p53 disruption has a dramatic effect on how
      glioblastoma cells process topoisomerase I inhibitor-mediated DNA damage.

PMID- 14961078
TI  - Frequent epigenetic inactivation of the RASSF1A tumor suppressor gene in
      Hodgkin's lymphoma.
AB  - Epigenetic inactivation of RASSF1A, a putative tumor suppressor with proapoptotic
      activity, is frequently observed in a number of solid tumors, including a variety
      of epithelial cancers, but has not been described in hematopoietic tumors. We
      have analysed the expression and methylation status of RASSF1A in Hodgkin's
      lymphoma (HL)-derived cell lines, primary HL tumors and serum samples from HL
      patients. RASSF1A transcription was detectable in only 2/6 HL cell lines.
      Methylation-specific PCR and bisulfite genomic sequencing revealed that the
      RASSF1A promoter was hypermethylated in all four RASSF1A-nonexpressing cell
      lines. 5-aza-2'-deoxycytidine treatment resulted in demethylation of the promoter
      and RASSF1A expression in these lines. Hypermethylation of RASSF1A was also
      detected in 34/52 (65%) primary HL tumors and in 2/22 serum samples from these
      patients. Microdissection of Hodgkin/Reed-Sternberg (HRS) cells from several of
      these cases confirmed that the RASSF1A hypermethylation we detected in the
      analysis of whole tumor originated from the tumor cell population. Although
      hypermethylation of RASSF1A was detected in 5/6 non-Hodgkin's lymphoma (NHL)
      derived cell lines, only rare primary NHL (1/10 of Burkitt's lymphoma, 1/12 of
      post-transplant lymphoma, 1/12 diffuse large B-cell lymphoma, 0/27 of nasal
      lymphoma, 0/8 follicular center cell lymphoma, 0/4 mantle cell lymphoma, 0/4
      anaplastic large cell (Ki-1+) lymphoma, 0/2 MALT lymphoma) showed
      hypermethylation of the promoter. No methylation was detected in any of the 14
      normal PBMC. These results point to an important role for epigenetic silencing of
      RASSF1A in the pathogenesis of HL. Inactivation of RASSF1A could be one mechanism
      by which HRS cells escape the apoptosis that should occur following nonproductive
      immunoglobulin gene rearrangements.

PMID- 14961079
TI  - Budget let-downs.

PMID- 14961080
TI  - Keys to capacity.

PMID- 14961081
TI  - Virologists call for vaccination in bid to beat bird flu epidemic.

PMID- 14961083
TI  - NASA steels itself for rough ride over Hubble's demise.

PMID- 14961082
TI  - Retraction signals end of cell-biology debate.

PMID- 14961084
TI  - Food panel calls for beefed up response to mad cow disease.

PMID- 14961085
TI  - Pacific dolphins make waves for US policy on Mexican tuna.

PMID- 14961086
TI  - Bioprospectors hunt for fair share of profits.

PMID- 14961087
TI  - Carp virus crisis prompts moves to avert global spread.

PMID- 14961088
TI  - Kofi Annan backs call for science push in developing countries.

PMID- 14961090
TI  - Green explosives: collateral damage.

PMID- 14961091
TI  - Climate change: the hot hand of history.

PMID- 14961092
TI  - Was Watson and Crick's model truly self-evident?

PMID- 14961093
TI  - Celebrating supernovae that changed the world.

PMID- 14961094
TI  - Europe needs a strategy to fight kidney disease.

PMID- 14961099
TI  - Extinction: past and present.

PMID- 14961100
TI  - Particle physics: lattice window on strong force.

PMID- 14961101
TI  - Medicine: genetic spotlight on a blood defect.

PMID- 14961103
TI  - Plant ecology: favoured aliens for the future.

PMID- 14961104
TI  - Planetary science: magnetic Mercury.

PMID- 14961106
TI  - Supramolecular chemistry: molecular merry-go-round.

PMID- 14961105
TI  - Device physics: the optical age of silicon.

PMID- 14961108
TI  - Molecular biology: ensuring error-free DNA repair.

PMID- 14961110
TI  - Networking opportunity.

PMID- 14961111
TI  - Neuroanatomy: brain asymmetry and long-term memory.
AB  - The asymmetrical positioning of neural structures on the left or right side of
      the brain in vertebrates and in invertebrates may be correlated with brain
      laterality, which is associated with cognitive skills. But until now this has not
      been illustrated experimentally. Here we describe an asymmetrically positioned
      brain structure in the fruitfly Drosophila and find that the small proportion of
      wild-type flies that have symmetrical brains with two such structures lack a
      normal long-term memory, although their short-term memory is intact. Our results
      indicate that brain asymmetry may be required for generating or retrieving long
      term memory.

PMID- 14961112
TI  - Evolutionary genetics: CCR5 mutation and plague protection.
AB  - A recent and prevalent mutation in the chemokine receptor CCR5 in humans of
      northern European ancestry has been proposed to provide protection against
      bubonic plague. Here we infect both normal and CCR5-deficient mice with the
      bacterium Yersinia pestis, the cause of the plague epidemics that wiped out one
      third of Europeans in the Middle Ages, and find no difference in either bacterial
      growth or survival time between the two groups. Unless the pathogenesis of
      Yersinia infection differs markedly between mice and humans, our results indicate
      that CCR5 deficiency in people is unlikely to protect against plague.

PMID- 14961113
TI  - Reversible redox energy coupling in electron transfer chains.
AB  - Reversibility is a common theme in respiratory and photosynthetic systems that
      couple electron transfer with a transmembrane proton gradient driving ATP
      production. This includes the intensely studied cytochrome bc1, which catalyses
      electron transfer between quinone and cytochrome c. To understand how efficient
      reversible energy coupling works, here we have progressively inactivated
      individual cofactors comprising cytochrome bc1. We have resolved millisecond
      reversibility in all electron-tunnelling steps and coupled proton exchanges,
      including charge-separating hydroquinone-quinone catalysis at the Q(o) site,
      which shows that redox equilibria are relevant on a catalytic timescale. Such
      rapid reversibility renders popular models based on a semiquinone in Q(o) site
      catalysis prone to short-circuit failure. Two mechanisms allow reversible
      function and safely relegate short-circuits to long-distance electron tunnelling
      on a timescale of seconds: conformational gating of semiquinone for both forward
      and reverse electron transfer, or concerted two-electron quinone redox chemistry
      that avoids the semiquinone intermediate altogether.

PMID- 14961114
TI  - The central image of a gravitationally lensed quasar.
AB  - A galaxy can act as a gravitational lens, producing multiple images of a
      background object. Theory predicts that there should be an odd number of images
      produced by the lens, but hitherto almost all lensed objects have two or four
      images. The missing 'central' images, which should be faint and appear near the
      centre of the lensing galaxy, have long been sought as probes of galactic cores
      too distant to resolve with ordinary observations. There are five candidates for
      central images, but in one case the third image is not necessarily the central
      one, and in the others the putative central images might be foreground sources.
      Here we report a secure identification of a central image, based on radio
      observations of one of the candidates. Lens models using the central image reveal
      that the massive black hole at the centre of the lensing galaxy has a mass of <2
      x 10(8) solar masses (M(o)), and the galaxy's surface density at the location of
      the central image is > 20,000M(o) pc(-2), which is in agreement with expections
      based on observations of galaxies that are much closer to the Earth.

PMID- 14961115
TI  - A high-speed silicon optical modulator based on a metal-oxide-semiconductor
      capacitor.
AB  - Silicon has long been the optimal material for electronics, but it is only
      relatively recently that it has been considered as a material option for
      photonics. One of the key limitations for using silicon as a photonic material
      has been the relatively low speed of silicon optical modulators compared to those
      fabricated from III-V semiconductor compounds and/or electro-optic materials such
      as lithium niobate. To date, the fastest silicon-waveguide-based optical
      modulator that has been demonstrated experimentally has a modulation frequency of
      only approximately 20 MHz (refs 10, 11), although it has been predicted
      theoretically that a approximately 1-GHz modulation frequency might be achievable
      in some device structures. Here we describe an approach based on a metal-oxide
      semiconductor (MOS) capacitor structure embedded in a silicon waveguide that can
      produce high-speed optical phase modulation: we demonstrate an all-silicon
      optical modulator with a modulation bandwidth exceeding 1 GHz. As this technology
      is compatible with conventional complementary MOS (CMOS) processing, monolithic
      integration of the silicon modulator with advanced electronics on a single
      silicon substrate becomes possible.

PMID- 14961117
TI  - Earthquake nucleation by transient deformations caused by the M = 7.9 Denali,
      Alaska, earthquake.
AB  - The permanent and dynamic (transient) stress changes inferred to trigger
      earthquakes are usually orders of magnitude smaller than the stresses relaxed by
      the earthquakes themselves, implying that triggering occurs on critically
      stressed faults. Triggered seismicity rate increases may therefore be most likely
      to occur in areas where loading rates are highest and elevated pore pressures,
      perhaps facilitated by high-temperature fluids, reduce frictional stresses and
      promote failure. Here we show that the 2002 magnitude M = 7.9 Denali, Alaska,
      earthquake triggered widespread seismicity rate increases throughout British
      Columbia and into the western United States. Dynamic triggering by seismic waves
      should be enhanced in directions where rupture directivity focuses radiated
      energy, and we verify this using seismic and new high-sample GPS recordings of
      the Denali mainshock. These observations are comparable in scale only to the
      triggering caused by the 1992 M = 7.4 Landers, California, earthquake, and
      demonstrate that Landers triggering did not reflect some peculiarity of the
      region or the earthquake. However, the rate increases triggered by the Denali
      earthquake occurred in areas not obviously tectonically active, implying that
      even in areas of low ambient stressing rates, faults may still be critically
      stressed and that dynamic triggering may be ubiquitous and unpredictable.

PMID- 14961116
TI  - A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron.
AB  - Molecular self-assembly offers a means of spontaneously forming complex and well
      defined structures from simple components. The specific bonding between DNA base
      pairs has been used in this way to create DNA-based nanostructures and to direct
      the assembly of material on the subnanometre to micrometre scale. In principle,
      large-scale clonal production of suitable DNA sequences and the directed
      evolution of sequence lineages towards optimized behaviour can be realized
      through exponential DNA amplification by polymerases. But known examples of three
      dimensional geometric DNA objects are not amenable to cloning because they
      contain topologies that prevent copying by polymerases. Here we report the design
      and synthesis of a 1,669-nucleotide, single-stranded DNA molecule that is readily
      amplified by polymerases and that, in the presence of five 40-mer synthetic
      oligodeoxynucleotides, folds into an octahedron structure by a simple
      denaturation-renaturation procedure. We use cryo-electron microscopy to show that
      the DNA strands fold successfully, with 12 struts or edges joined at six four-way
      junctions to form hollow octahedra approximately 22 nanometres in diameter.
      Because the base-pair sequence of individual struts is not repeated in a given
      octahedron, each strut is uniquely addressable by the appropriate sequence
      specific DNA binder.

PMID- 14961118
TI  - Ramp initiation in a thrust wedge.
AB  - Collisional mountain belts are characterized by fold and thrust belts that grow
      through sequential stacking of thrust sheets from the interior (hinterland) to
      the exterior (foreland) of the mountain belt. Each of these sheets rides on a
      fault that cuts up through the stratigraphic section on inclined ramps that join
      a flat basal fault at depth. Although this stair-step or ramp-flat geometry is
      well known, there is no consensus on why a particular ramp forms where it does.
      Perturbations in fault shape, stratigraphy, fluid pressure, folding, and surface
      slope have all been suggested as possible mechanisms. Here we show that such pre
      existing inhomogeneities, though feasible causes, are not required. Our computer
      simulations show that a broad foreland-dipping plastic strain band forms at the
      surface near the topographic inflection produced by the previous ramp. This
      strain band then migrates towards the rigid base, where the plastic strain is
      preferentially concentrated in a thrust ramp. Subsequent ramps develop toward the
      foreland in a similar fashion. Syntectonic erosion and deposition may strongly
      control the location of thrust ramps by enhancing or removing the surface point
      of initiation.

PMID- 14961119
TI  - New light shed on the oldest insect.
AB  - Insects are the most diverse lineage of all life in numbers of species, and
      ecologically they dominate terrestrial ecosystems. However, how and when this
      immense radiation of animals originated is unclear. Only a few fossils provide
      insight into the earliest stages of insect evolution, and among them are
      specimens in chert from Rhynie, Scotland's Old Red Sandstone (Pragian; about 396
      407 million years ago), which is only slightly younger than formations harbouring
      the earliest terrestrial faunas. The most well-known animal from Rhynie is the
      springtail Rhyniella praecursor (Entognatha; Collembola), long considered to be
      the oldest hexapod. For true insects (Ectognatha), the oldest records are two
      apparent wingless insects from later in the Devonian period of North America.
      Here we show, however, that a fragmentary fossil from Rhynie, Rhyniognatha
      hirsti, is not only the earliest true insect but may be relatively derived within
      basal Ectognatha. In fact, Rhyniognatha has derived characters shared with winged
      insects, suggesting that the origin of wings may have been earlier than
      previously believed. Regardless, Rhyniognatha indicates that insects originated
      in the Silurian period and were members of some of the earliest terrestrial
      faunas.

PMID- 14961120
TI  - An optimal bronchial tree may be dangerous.
AB  - The geometry and dimensions of branched structures such as blood vessels or
      airways are important factors in determining the efficiency of physiological
      processes. It has been shown that fractal trees can be space filling and can
      ensure minimal dissipation. The bronchial tree of most mammalian lungs is a good
      example of an efficient distribution system with an approximate fractal
      structure. Here we present a study of the compatibility between physical
      optimization and physiological robustness in the design of the human bronchial
      tree. We show that this physical optimization is critical in the sense that small
      variations in the geometry can induce very large variations in the net air flux.
      Maximum physical efficiency therefore cannot be a sufficient criterion for the
      physiological design of bronchial trees. Rather, the design of bronchial trees
      must be provided with a safety factor and the capacity for regulating airway
      calibre. Paradoxically, our results suggest that bronchial malfunction related to
      asthma is a necessary consequence of the optimized efficiency of the tree
      structure.

PMID- 14961121
TI  - Identification of an angiogenic factor that when mutated causes susceptibility to
      Klippel-Trenaunay syndrome.
AB  - Angiogenic factors are critical to the initiation of angiogenesis and maintenance
      of the vascular network. Here we use human genetics as an approach to identify an
      angiogenic factor, VG5Q, and further define two genetic defects of VG5Q in
      patients with the vascular disease Klippel-Trenaunay syndrome (KTS). One mutation
      is chromosomal translocation t(5;11), which increases VG5Q transcription. The
      second is mutation E133K identified in five KTS patients, but not in 200 matched
      controls. VG5Q protein acts as a potent angiogenic factor in promoting
      angiogenesis, and suppression of VG5Q expression inhibits vessel formation. E133K
      is a functional mutation that substantially enhances the angiogenic effect of
      VG5Q. VG5Q shows strong expression in blood vessels and is secreted as vessel
      formation is initiated. VG5Q can bind to endothelial cells and promote cell
      proliferation, suggesting that it may act in an autocrine fashion. We also
      demonstrate a direct interaction of VG5Q with another secreted angiogenic factor,
      TWEAK (also known as TNFSF12). These results define VG5Q as an angiogenic factor,
      establish VG5Q as a susceptibility gene for KTS, and show that increased
      angiogenesis is a molecular pathogenic mechanism of KTS.

PMID- 14961122
TI  - A conserved siRNA-degrading RNase negatively regulates RNA interference in C.
      elegans.
AB  - In many organisms, introducing double-stranded RNA (dsRNA) causes the degradation
      of messenger RNA that is homologous to the trigger dsRNA--a process known as RNA
      interference. The dsRNA is cleaved into short interfering RNAs (siRNAs), which
      hybridize to homologous mRNAs and induce their degradation. dsRNAs vary in their
      ability to trigger RNA interference: many mRNA-targeting dsRNAs show weak
      phenotypes, and nearly all mRNAs of the Caenorhabditis elegans nervous system are
      refractory to RNA interference. C. elegans eri-1 was identified in a genetic
      screen for mutants with enhanced sensitivity to dsRNAs. Here we show that eri-1
      encodes an evolutionarily conserved protein with domains homologous to nucleic
      acid-binding and exonuclease proteins. After exposure to dsRNA or siRNAs, animals
      with eri-1 mutations accumulate more siRNAs than do wild-type animals. C. elegans
      ERI-1 and its human orthologue degrade siRNAs in vitro. In the nematode worm, ERI
      1 is predominantly cytoplasmic and is expressed most highly in the gonad and a
      subset of neurons, suggesting that ERI-1 siRNase activity suppresses RNA
      interference more intensely in these tissues. Thus, ERI-1 is a negative regulator
      that may normally function to limit the duration, cell-type specificity or
      endogenous functions of RNA interference.

PMID- 14961123
TI  - Cytoplasmic dynein functions as a gear in response to load.
AB  - Cytoskeletal molecular motors belonging to the kinesin and dynein families
      transport cargos (for example, messenger RNA, endosomes, virus) on polymerized
      linear structures called microtubules in the cell. These 'nanomachines' use
      energy obtained from ATP hydrolysis to generate force, and move in a step-like
      manner on microtubules. Dynein has a complex and fundamentally different
      structure from other motor families. Thus, understanding dynein's force
      generation can yield new insight into the architecture and function of
      nanomachines. Here, we use an optical trap to quantify motion of polystyrene
      beads driven along microtubules by single cytoplasmic dynein motors. Under no
      load, dynein moves predominantly with a mixture of 24-nm and 32-nm steps. When
      moving against load applied by an optical trap, dynein can decrease step size to
      8 nm and produce force up to 1.1 pN. This correlation between step size and force
      production is consistent with a molecular gear mechanism. The ability to take
      smaller but more powerful strokes under load--that is, to shift gears--depends on
      the availability of ATP. We propose a model whereby the gear is downshifted
      through load-induced binding of ATP at secondary sites in the dynein head.

PMID- 14961124
TI  - Patching a leaky pipeline.

PMID- 14961125
TI  - Baywatch: San Francisco.

PMID- 14961126
TI  - Graduate journal: seeking perspective.

PMID- 14961127
TI  - Bricks and mortar.

PMID- 14961129
TI  - Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY
      adenine DNA glycosylase.
AB  - The genomes of aerobic organisms suffer chronic oxidation of guanine to the
      genotoxic product 8-oxoguanine (oxoG). Replicative DNA polymerases misread oxoG
      residues and insert adenine instead of cytosine opposite the oxidized base. Both
      bases in the resulting A*oxoG mispair are mutagenic lesions, and both must
      undergo base-specific replacement to restore the original C*G pair. Doing so
      represents a formidable challenge to the DNA repair machinery, because adenine
      makes up roughly 25% of the bases in most genomes. The evolutionarily conserved
      enzyme adenine DNA glycosylase (called MutY in bacteria and hMYH in humans)
      initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine
      base from the DNA backbone. A central issue concerning MutY function is the
      mechanism by which A*oxoG mispairs are targeted among the vast excess of A*T
      pairs. Here we report the use of disulphide crosslinking to obtain high
      resolution crystal structures of MutY-DNA lesion-recognition complexes. These
      structures reveal the basis for recognizing both lesions in the A*oxoG pair and
      for catalysing removal of the adenine base.

PMID- 14961130
TI  - [New regulation for multicenter clinical trials and its repercussions on the
      function of current clinical trial ethics committees].

PMID- 14961131
TI  - [Plants with antimicrobial action].

PMID- 14961132
TI  - [Class 1 integrons in Enterobacteriaceae and its association with multidrug
      resistance and conjugative plasmids].
AB  - The prevalence of antimicrobial resistance genes is a cause of concern. The
      combination of antimicrobial resistance genes and mobile genetic elements leads
      to their widespread presence in different bacterial species, in which integrons
      are a new and important element. We studied the presence of integrons in 123
      unrelated enterobacteria and identified them in 20.3% of the strains. The
      combination of integrons and multidrug resistance was shown to be statistically
      significant (p <0.001). Integron-positive isolates were statistically (p <0.05)
      more likely to be resistant to amoxicillin-clavulanic acid, quinolones and
      trimethoprim-sulfamethoxazole. All the integrons were identified in conjugative
      plasmids. The prevalence of integrons increased from 21.2% in 1992-1994 to 72% in
      1995-1997 (p <0.001). The aacC1 and aacC2 genes were identified in 80% of the
      integrons. The relationship between integrons and conjugative plasmids is a
      matter of concern because it could contribute to the dissemination of
      antimicrobial resistance genes among different bacterial populations.

PMID- 14961133
TI  - [Different antibiotic resistance mechanisms associated with integrons in clinical
      isolates of Salmonella typhimurium].
AB  - Antibiotic resistance in clinical isolates of Salmonella typhimurium has steadily
      risen in recent years. Some of the resistance genes may be carried into
      integrons. In this study, integrons, both from 10 epidemiologically related and
      unrelated S. typhimurium clinical isolates, were characterized, showing that
      epidemiologically different strains can carry the same integron, and that
      epidemiologically related strain can carry different integrons. Among the
      resistance genes detected in this study were genes encoding b-lactamases (bla(oxa
      30) in two strains, and bla(pse-1) in five strains, one of which was carrying
      this cassette in two different integrons); aminoglycoside-modifying enzymes
      (aadA2 in four strains, one of which was carrying this cassette in two different
      integrons, and aadA1 in six strains); as well dihydrofolate reductases (dfrAI in
      three strains).

PMID- 14961134
TI  - [Meta-analysis of clarithromycin compared to other antibiotics for the treatment
      of lower respiratory tract infections].
AB  - Clarithromycin is a macrolide antibiotic commonly used for the treatment of
      respiratory infections. The aim of this study was to assess its effectiveness for
      the treatment of lower respiratory tract infections. A number of meta-analyses of
      clinical trials comparing clarithromycin to the antibiotics most frequently used
      in the treatment of lower respiratory tract infections, such as cephalosporins,
      amoxicillin-clavulanic acid, erythromycin and azithromycin, have been performed.
      Clarithromycin's effectiveness for the treatment of lower respiratory tract
      infections was better than that for cephalosporins (OR = 1.43; 95% CI = 1.09
      1.86) and, although not to the same extent, that for amoxicillin-clavulanic acid
      (OR = 1.58; 95% CI = 0.92-2.70); however, the efficacy was only similar to that
      shown for azithromycin (OR = 0.57; 95% CI = 0.19-1.68). The fourth meta-analysis
      compared the effectiveness of clarithromycin to that of erythromycin for the
      treatment of pneumonia and showed a superior odds ratio in favor of
      clarithromycin (OR = 1.46; 95% CI = 0.97-2.2). Meta-analyses comparing
      clarithromycin's safety to that of the same drugs in the same conditions used in
      the assessment of effectiveness showed a similar incidence of adverse events
      compared to amoxicillin-clavulanic acid, and azithromycin, a slightly lower
      incidence compared to erythromycin, and a slightly higher incidence compared to
      cephalosporins. In conclusion, these meta-analyses show that clarithromycin is an
      effective and safe antibiotic for the treatment of lower respiratory tract
      infections. Furthermore, a new once-daily dose formulation with a positive impact
      on therapeutic compliance is currently available, making clarithromycin a first
      line treatment for lower respiratory tract infections.

PMID- 14961135
TI  - [Serotypes and antibiotic susceptibility of Streptococcus pneumoniae in children
      in the health district of Valencia and Castellon, Spain: a multicenter,
      prospective trial].
AB  - A study was conducted to determine the serotypes, the coverage of the heptavalent
      conjugate vaccine (VCN 7-v) and the antibiotic susceptibility of Streptococcus
      pneumoniae in children (<15 years) in the health districts of the provinces of
      Castellon and Valencia, Spain, from June 1999 to December 2002. A total of 271
      strains were evaluated, 15.5% of which were invasive, 63.5% were of respiratory
      origin and 22.5% were from conjunctival and otitic exudates; 67.2% of the strains
      were found in children younger than 2 years of age. The distribution of the
      serotypes showed slight changes according to age and the origin of the sample:
      the most common serotypes were 19, 6, 23, 14, 3, 9 and 11; however, in children
      younger than 2 years of age the order changed to 19, 6, 14 and 23, 9, 11 and 3,
      and in the invasive strains to 19, 6, 14, 3 and 23. A total of 27.2% of the
      stains were susceptible to the ten antibiotics tested. For penicillin, reduced
      susceptibility was found in 50.4% and high resistance in 5.8%; 98.3% were
      susceptible to ampicillin and amoxicillin-clavulanic acid, and 80.7% to
      cefuroxime; 52.5% were resistant to erythromycin and 43.7% to clindamycin. No
      strains were resistant to rifampicin, vancomycin, levofloxacin or cefotaxime. The
      most susceptible serotypes were 3 and 11, and the most resistant was 14 (which
      consistently showed resistance to an antibiotic), 19, 6 and 23. According to
      these data, the theoretical coverage of VCN 7-v would be 80.1% in children
      younger than 2 years and 73.43% in those aged 0-14 years.

PMID- 14961136
TI  - [Trends in antimicrobial resistance of Pseudomonas aeruginosa, Escherichia coli
      and Bacteroides fragilis (1997-2001)].
AB  - A study was conducted from 1997 to 2001 on the trends of the antibiotic
      resistance of Pseudomonas aeruginosa, Escherichia coli and Bacteroides fragilis
      in a Spanish multicenter study involving 26 hospitals. During the five years of
      the study the susceptibility by 81,779 strains of P. aeruginosa, 306,689 strains
      of E. coli and 2866 strains of B. fragilis to at least one antibiotic were
      studied. When the three microorganisms were considered together, meropenem
      (3.49%), piperacillin-tazobactam (5.54%) and imipenem (5.27%) were the
      antibiotics to which they showed the lowest resistance rate.

PMID- 14961137
TI  - [Prevalence and treatment of Gram-positive infections in internal medicine
      departments of Spanish hospitals: IGP Study].
AB  - This study aimed to identify therapeutic approaches and the tendencies of Gram
      positive infections in Spanish hospitals in terms of prevalence, origin, location
      and etiology, as well as the characteristics of patients with these infections,
      their underlying illnesses, the severity and predisposing factors. We used
      statistical analysis to compare the results of two multicenter prevalence
      studies, the first from 1994-1995, and the second in 1998. We found a
      statistically significant decrease in the percentage of infected patients (45.8%
      vs. 32.8%; p <0.001), but an increase in infections by Gram-positive
      microorganisms (14.4% vs. 20.6%; p <0.001), which was reflected in the increased
      use of glycopeptides (17.1% vs. 31.2%; p = 0.002). The use of quinolones also
      increased. The most common underlying illnesses were heart disease and diabetes
      mellitus, and there was a reduction in the number of patients infected by HIV and
      in users of parenteral medication. The decrease in outpatient infections
      indicated that nosocomial infection was more frequent in the second study, in
      which the number of predisposing factors increased (52.3% vs. 79.2%; p <0.001),
      the most common of which were peripheral line, immobilization and a bladder
      catheter. Bacteremia was the most frequent infection, and there was a reduction
      in lower respiratory tract infections and an increase in skin and soft tissue
      infections. Staphylococcus aureus was the most frequently found microorganism and
      showed a significant increase in incidence (27.2% vs. 47.9%; p <0.001), whereas
      pneumococcus showed a decrease (15.0% vs. 5.2%; p = 0.012). It was concluded that
      despite the decrease in the percentage of infected patients and severely ill
      patients, there is an increase in Gram-positive infections, especially
      bacteremia, and in the use of more aggressive treatments. This may reflect the
      increase in resistant isolates.

PMID- 14961138
TI  - Activity of oral antibiotics against respiratory tract pathogens in Spain.
AB  - The aim of this study was to carry out a nationwide survey to assess the
      susceptibility of clinical isolates of four respiratory pathogens against nine
      antibiotics. Eight Spanish centers participated in the study, collecting a total
      of 977 isolates of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus
      influenzae and Moraxella catarrhalis. The susceptibility of S. pneumoniae to
      penicillin was 37.46% susceptible, 30.43% intermediate and 32.11% resistant.
      MIC(90) of all antibiotics against this microorganism were 48 mg/l, except
      cefaclor, cefixime and azithromycin. For S. pyogenes, all the strains were
      susceptible to penicillins and cephalosporins, and azithromycin was the least
      active with a rate of resistance of 11.43%. A total of 95 isolates of H.
      influenzae were betalactamase positive (26.32%). With regard to M. catarrhalis,
      only penicillin and amoxicillin showed MICs(90) >=8 mg/l.

PMID- 14961139
TI  - [Antimicrobial susceptibility of Pseudomonas aeruginosa clinical isolates in
      Murcia, Spain].
AB  - The source and antimicrobial susceptibility of 1293 clinical isolates of
      Pseudomonas aeruginosa obtained from 1996 to 1999 were studied. Urine was the
      most common source for outpatient isolates (61.2%), while for hospitalized
      patients respiratory samples were the most frequent (40.2%). The most active
      antimicrobials with resistance rates <=10% were ceftazidime, imipenem, tobramycin
      and amikacin. By contrast, aztreonam, ciprofloxacin and gentamicin showed
      resistance levels >10%. The percentages of resistance to ceftazidime, aztreonam
      and imipenem in isolates from inpatients and from patients in the intensive care
      unit were significantly higher than those in isolates from outpatients and other
      clinical departments. Comparison of susceptibility data from 1996 to 1999 showed
      a significant increase in the resistance rate for all of the antibiotics studied
      but imipenem.

PMID- 14961140
TI  - [Current status of Pseudomonas aeruginosa resistance to antibiotics].
AB  - Pseudomonas aeruginosa is responsible for numerous infections, mainly in
      hospitals and in immunocompromised patients. This pathogen has a great ability to
      acquire resistance. Given the increase in prevalence of multiresistant isolates,
      a continuous analysis of the susceptibility of P. aeruginosa to antimicrobial
      drugs is required. We therefore evaluated all the P. aeruginosa isolates from
      clinical samples taken at our hospital in 2002, and included only one sample per
      patient. We studied the susceptibility of P. aeruginosa to 11 active
      antimicrobial drugs. Identification of the isolate and determination of
      susceptibility were carried out using an automated system (VITEK 2, bioMerieux).
      Overall, the antibiotic with the highest in vitro activity was piperacillin
      tazobactam. The percentage of multiresistant isolates (resistance to at least two
      groups of antibiotics) was 20.9%. In samples taken from the ICU, it showed high
      resistance to imipenem (20%). P. aeruginosa isolated from abscesses was extremely
      resistant to gentamicin (41.6%). The resistance of P. aeruginosa to antimicrobial
      drugs is inconsistent as it depends on the source of the isolates and the type of
      clinical samples. Consequently, individualized monitoring should be conducted.

PMID- 14961141
TI  - [About the second consensus document for antimicrobial use in exacerbations of
      COPD].

PMID- 14961142
TI  - [Mycobacterium tuberculosis resistance in a hospital in Leon, Spain].

PMID- 14961143
TI  - [Initial empirical antibiotic treatment of community-acquired pneumonia in
      immunocompetent adult patients].

PMID- 14961144
TI  - [Diagnostics, treatment and prevention of infection in articular prostheses].

PMID- 14961145
TI  - Monitoring oral anticoagulant therapy--INR values for the Owren prothrombin time.

PMID- 14961146
TI  - Coagulopathy of sepsis.
AB  - Disseminated intravascular coagulation (DIC) is a common phenomenon in patients
      with sepsis, but the clinical implications of this condition are not clear.
      Clinical trials with coagulation inhibitors have failed to show a significant
      benefit concerning survival. DIC is primarily a laboratory diagnosis, based on
      the combination of elevated fibrin-related markers (FRM), with decreased
      procoagulant factors and platelets. Non-overt DIC is observed in most patients
      with sepsis, whereas overt DIC is less frequent. Patients with overt DIC may
      display consumption coagulopathy and purpura fulminans. Consumption coagulopathy
      is a bleeding disorder caused by low levels of platelets and procoagulant factors
      associated with massive coagulation activation. Purpura fulminans is caused by
      widespread microvascular thrombosis, resulting in tissue necrosis. Treatment with
      drotrecogin alfa (activated) improves survival and other outcome parameters in
      severe sepsis, including a subgroup of patients fulfilling the laboratory
      criteria of overt DIC. No randomized trials demonstrating effective therapies in
      consumption coagulopathy have been published. Bleeding patients with consumption
      coagulopathy are most frequently treated with platelet transfusions and various
      plasma products including fresh frozen plasma and coagulation factor
      concentrates. Based on case reports, treatment with drotrecogin alfa (activated)
      or substitution of protein C have been recommended for adjuvant treatment of
      sepsis-related purpura fulminans.

PMID- 14961147
TI  - Systematic review of studies of self-management of oral anticoagulation.
AB  - This work is aimed at assessing the evidence for the possible improvement of
      therapeutic control of anticoagulation, reduction of major bleedings,
      thromboembolism and improvement of treatment-related quality of life in patients
      with self-managed oral anticoagulation therapy versus oral anticoagulation
      patients on routine care. Randomised controlled trials (RCTs) were identified
      using the COCHRANE LIBRARY, MEDLINE and EMBASE from 1966 to 2003. RCTs were
      selected involving patients with oral anticoagulation, which were designed to
      compare a self-management group to a routine care group. Abstracts and keywords
      were screened and, in the case of potential inclusion, evaluated. We identified
      nine potentially relevant trials. Five were excluded for the following reasons:
      double publication, the patients involved performed only self-testing, or the
      results of the trial were only published as an abstract. Ultimately, four
      randomised controlled studies fulfilled the criteria for inclusion.
      Anticoagulation control: Statistical analysis was not possible because of the
      great variety of international normalised ratio measurements per patient between
      the different studies. Comparing the four studies, there was no difference in
      oral anticoagulation control between self-management care and management by a
      specialised anticoagulation clinic. In comparison with routine care by general
      practitioners, self-management care was found to be better. Major bleeding,
      arterial and venous thromboembolism: Data were available for all studies;
      however, the studies were either underpowered or obviously not valid and
      therefore not suitable for statistical analysis. Treatment-related quality of
      life: Data were available for two studies, which showed that self-management
      could clearly improve treatment-related quality of life. Patients' self
      management can improve the quality of oral anticoagulation as an indirect
      parameter of a reduced risk for thromboembolic and bleeding complications. Self
      management oral anticoagulation treatment is safe and improves treatment-related
      quality of life. Patients' self-management is safe and can improve the quality of
      anticoagulation control, however, no valid long term study has yet actually
      demonstrated reduction of bleeding and thromboembolic events.

PMID- 14961148
TI  - Thrombin binding to GPIbalpha induces integrin alphaIIbbeta3 dependent platelet
      adhesion to fibrin in ex vivo flowing whole blood.
AB  - We have investigated the role of the thrombin/GPIbalpha interaction in the
      adhesion of platelets to fibrin in a whole blood ex vivo perfusion model at a
      shear rate of 280 s(-1). Blood was perfused through parallel-plate chambers
      containing coverslips coated with cells expressing tissue factor, leading to the
      generation of thrombin and thus, deposition of fibrin onto the exposed cells.
      Adhesion of platelets to fibrin and thrombus growth were analyzed. Interestingly,
      when GPIbalpha was removed from the platelet surface by action of mocarhagin,
      platelet adhesion on fibrin was inhibited. Furthermore, a monoclonal antibody,
      VM16d, directed against the thrombin binding site on GPIbalpha also inhibited
      platelet adhesion on fibrin, showing the importance of the thrombin/GPIbalpha
      interaction.We then looked at the involvement of alphaIIbbeta3 and showed that
      platelet adhesion and thrombus growth on fibrin were inhibited by the
      dodecapeptide, whereas lamifiban only inhibited the growth of the platelet
      thrombus. These results indicated that binding of thrombin to GPIbalpha induced
      an intracellular signaling leading to the interaction of the platelet integrin
      alphaIIbbeta3 with the fibrin-dodecapeptide sequence.

PMID- 14961149
TI  - Activated protein C generation is greatly decreased in plasma from newborns
      compared to adults in the presence or absence of endothelium.
AB  - Activated protein C (APC) generation strongly affects sepsis and thrombosis by
      inhibition of thrombin generation. However, it is unclear if there are age
      related differences in effectiveness of protein C (PC). We studied age effects on
      plasma APC generation +/- endothelium. Defibrinated (Ancrod) plasma (from adults
      or newborns (umbilical cord)) was recalcified with buffer containing tissue
      factor +/- thrombomodulin (TM) on either plastic or endothelium (HUVEC) at 37
      degrees C. Timed subsamples of reaction mixture were taken into either heparin
      EDTA or FFRCMK-EDTA solutions and analyzed for APC-PC inhibitor (APC-PCI) or APC
      alpha1 antitrypsin (APC-alpha1 AT) by ELISAs. Since heparin converts free APC to
      APC-PCI, the difference in APC-PCI measured in heparin-EDTA and FFRCMK-EDTA
      samples was equal to free active APC. APC-alpha2 macroglobulin (APC-alpha2M) was
      measured as remaining chromogenic activity in heparin-EDTA. Free APC, APC-PCI and
      APC-alpha1 AT were decreased in newborn compared to adult plasma on plastic.
      However, APC-alpha2M made up a larger fraction of inhibitor complexes in new-born
      plasma. On endothelium, significantly more APC, APC-PCI and APC-alpha1AT were
      generated in either plasma compared to that on plastic with excess added TM. APC,
      APC-PCI and APC-alpha1AT were also reduced and total APC-alpha2M increased in
      newborn plasma on HUVEC. Addition of PC to newborn plasma gave APC generation
      similar to adult plasma. Thus, free APC, APC-PCI and APC-alpha1AT generation is
      reduced in newborn compared to adult plasma with or without endothelium, likely
      due to reduced plasma PC levels. Endothelium enhances APC generation, regardless
      of plasma type, possibly because of cell surface factors such as TM, phospholipid
      and endothelial PC receptor.

PMID- 14961150
TI  - The TF-603A/G gene promoter polymorphism and circulating monocyte tissue factor
      gene expression in healthy volunteers.
AB  - Three single nucleotide polymorphisms (-603A/G, -1322C/T, -1812C/T) and one
      deletion/insertion polymorphism (-1208D/I) are present in the tissue factor (TF)
      gene promoter sequence. These polymorphisms are in complete linkage
      disequilibrium, determining two haplotypes with almost equal frequency. The 
      603A/-1208D/-1322C/-1812C haplotype, presently defined as TF-603A, has been
      linked to venous thromboembolic disease, with a potentially protecting effect.
      The effects of the TF-603A/G gene polymorphism on monocyte gene expression and on
      a whole-blood clotting time (WBCT) are not known. We determined the WBCT in basal
      conditions (H0) and after 4 hours of LPS stimulation ex vivo (H4LPS) on blood
      samples from 100 young healthy caucasian male subjects on 2 visits, 7 days apart.
      Monocyte TF mRNA was quantified at H0 and H4LPS by real-time quantitative reverse
      transcription PCR. The monocyte TF mRNA values determined at the first and second
      visits were concordant. In H4LPS samples, TF mRNA levels were increased 70-fold.
      The TF-603A haplotype was associated with 40%-lower TF mRNA levels at H0
      (P=0.0002) and this association followed the same trend but was no longer
      significant at H4LPS. At H4LPS, TF mRNA levels were associated with WBCT
      shortening (P=0.0003). WBCT at H0 was not concordant over time, precluding any
      genotype-phenotype analysis. WBCT at H4LPS was concordant over time but was not
      related to the TF-603A/G polymorphism. The TF-603A/G gene promoter polymorphism
      thus significantly influences constitutive TF gene expression in human monocytes
      but has no major effect on TF gene expression or on WBCT in LPS stimulated
      conditions.

PMID- 14961151
TI  - Anti-prothrombin antibodies as a potential risk factor of recurrent venous
      thromboembolism.
AB  - The role of antiprothrombin (aPT) antibodies in the development of venous
      thromboembolism (VTE) is still uncertain. The aim of this study was to evaluate
      the potential role of aPT antibodies in the development of recurrent
      thromboembolism. Out of 236 consecutive symptomatic patients with an episode of
      acute VTE, antiphospholipid antibodies were found in 85 (36.0%), of whom 24 were
      carriers of aPT antibodies (10.2% of the entire cohort). A history of previous
      thromboembolism was identified in 56 patients (23.7%). The prevalence of previous
      thromboembolism was significantly higher in carriers than in non-carriers of
      antiphospholipid antibodies (OR=2.4; 95% CI, 1.3 to 4.4). Of the 24 patients with
      aPT antibodies, 12 had a history of previous thromboembolism. In a multivariate
      logistic regression analysis, in which the other categories of antiphospholipid
      antibodies were taken into account, as well as the patient's age, sex, and the
      modality of clinical presentation, it was found that the presence of aPT
      antibodies was significantly associated with the prevalence of prior
      thromboembolism (OR=3.3; 95% CI, 1.3 to 8.6). Since aPT antibodies are more
      commonly identifiable in patients with multiple thrombotic episodes, they are a
      likely risk factor for recurrent thromboembolism.

PMID- 14961152
TI  - Extracorporeal adsorption of anti-factor VIII allo-antibodies on randomly
      functionalized polystyrene resins.
AB  - The occurrence of anti-factor VIII (FVIII) allo-antibodies is a severe
      complication of the treatment of haemophilia A patients, leading to the
      inhibition of transfused FVIII activity. The effective elimination of these
      inhibitory antibodies plays a decisive role in the management of affected
      patients. To achieve this, immunoadsorption devices employing synthetic
      adsorbers, which selectively eliminate inhibitors, are of interest in the
      treatment strategy of haemophilia A patients with inhibitors. Adsorbers
      consisting of polystyrene-based beads substituted with sulphonate and L-tyrosyl
      methylester groups, which mimic part of epitope of FVIII molecule recognized by
      inhibitors, exhibit selective binding capacities towards anti-FVIII antibodies.
      The adsorption of FVIII inhibitors was investigated by simulating an
      extracorporeal circulation of haemophilic plasma over these functionalized
      resins. These innovative adsorbers are able to remove around 25% of anti-FVIII
      antibodies in 15 minutes depending on the plasma tested. Furthermore, they do not
      modify the amount of essential plasmatic proteins or residual immunoglobulins G.
      Experiments which were carried out using different plasmas with various inhibitor
      titres demonstrate a good reproducibility regarding the adsorption capacity of
      the synthetic resin. The characteristics of adsorption are similar on either
      native or regenerated resins. Both the purely synthetic nature of the resin and
      its easy processability demonstrate the real advantages over currently available
      protocols. This synthetic adsorber is a major technological advance in selective
      removal of FVIII inhibitory antibodies.

PMID- 14961153
TI  - Factor VIII expression in liver disease.
AB  - Liver disease is associated with markedly elevated plasma factor VIII (FVIII)
      levels, whereas the synthesis of many other coagulation factors and proteins is
      reduced. In order to define the mechanism of FVIII increase, we have determined
      the expression levels of FVIII, both at mRNA and protein level, in patients with
      liver disease who underwent partial liver resection. In addition, the expression
      of von Willebrand factor (VWF) and low density lipoprotein receptor-related
      protein (LRP), proteins known for their ability to modulate FVIII plasma levels,
      were examined. Tissue samples for RNA extraction were obtained from 4 patients
      with cirrhosis, 9 patients with liver failure without cirrhosis and 6 patients
      with liver metastasis of a colon or rectum carcinoma (control group). In patients
      with liver cirrhosis hepatic FVIII and LRP mRNA levels were significantly lower
      than controls (p < or = 0.010), while VWF mRNA was significantly higher (p < or =
      0.050). Immunohistochemical analysis revealed that cellular VWF protein
      distribution was also increased in cirrhotic livers compared to liver tissue from
      patients with non-cirrhotic liver disease. In cirrhotic tissue enlarged portal
      veins appeared to overgrow FVIII producing sinusoidal endothelial cells.
      Similarly, the number of LRP-producing cells appeared to be lower in cirrhotic
      tissue than in controls. The plasma concentration of both FVIII and VWF was
      significantly higher in patients with cirrhosis than control subjects (p = 0.038
      and 0.010 respectively). These results demonstrate that elevated plasma FVIII
      levels in liver cirrhosis are associated with increased hepatic biosynthesis of
      VWF and decreased expression of LRP, rather than increased FVIII synthesis.

PMID- 14961154
TI  - Titre of anti-heparin/PF4-antibodies and extent of in vivo activation of the
      coagulation and fibrinolytic systems.
AB  - Heparin-induced thrombocytopenia (HIT) is mediated by antibodies directed against
      the heparin/platelet factor 4 (PF4) complex. Our aim was to investigate whether
      the antibody titre is associated with the degree of in vivo thrombin generation.
      We measured the anti-heparin/PF4-antibody titre, prothrombin fragments F1+2,
      thrombin-antithrombin (TAT) complexes and D-dimers in plasma samples from 225
      patients with suspected HIT. Antibody titres as detected by a particle gel
      immunoassay strongly correlated with optical density values measured by ELISA
      (r=0.84, p<0.0001). Patients with titres > or =4 (n=44) had significantly higher
      median levels of F1+2 (2.49 nmol/l), TAT (13.01 microg/l) and D-dimers (3340
      microg/l) compared to patients with undetectable antibodies (n=148; F1+2 1.61
      nmol/l, TAT 4.95 micro g/l, D-dimers 1911 micro g/l; p<0.0001 for all
      comparisons) or patients with titres of 1-2 (n=33; F1+2 1.44 nmol/l, p=0.0014;
      TAT 4.37 microg/l, p=0.0018; D-dimers 2231 microg/l, p=0.0016). Multivariate
      analysis indicated the anti-heparin/PF4-antibody titre as an independent
      predictor for F1+2 (p=0.0036), TAT (p=0.0176) and D-dimer (p=0.0003) levels. This
      relationship remained statistically significant after exclusion of patients with
      concomitant prothrombotic conditions and/or thromboembolic complications during
      heparin treatment. These data demonstrate that high anti-heparin/PF4-antibody
      titres are independently associated with an increased in vivo thrombin
      generation. Rapid determination of the anti-heparin/PF4-antibody titre could help
      guide clinical management, identifying a subset of HIT-patients who are at high
      risk of developing thromboembolic complications and possibly require alternative
      anticoagulation in therapeutic dosage even in the context of isolated HIT.

PMID- 14961155
TI  - Efficacy of AT in pre-eclampsia: a case-control prospective trial.
AB  - Pre-eclampsia is an extremely severe condition. It is associated with vasospasm,
      activation of the coagulation system and abnormal haemostasis. In pre-eclamptic
      patients increased plasmatic concentrations of fibronectin, laminin, von
      Willebrand factor (VWF) and endothelin are observed. Experimental studies on rats
      have also shown that the doses of antithrombin III (AT) needed to mediate anti
      inflammatory processes are much higher than those required to obtain the anti
      coagulant effect. The study aimed to evaluate the clinical efficacy of treatment
      with high AT doses (HD) in comparison with standard doses (SD). The primary
      endpoint was the prolongation of pregnancy defined as time (in days) from
      enrollment to delivery and to assess the maternal bleeding at and after delivery.
      The secondary endpoint was to demonstrate a role for AT in controlling
      haemostasis at conventional doses, and the inflammatory state at higher doses.
      The biochemical parameters assessed were: AT activity (%), Fibronectin (Fn),
      Fibrinogen, D-dimer, Uricemia, Proteinuria 24h, Protein C Reactive (PCR),
      Granulocyte Elastase and Endothelin. This study included 23 pre-eclamptic women.
      Patients were randomly subdivided into two groups: 10 patients ("cases") were
      treated with high doses of AT (6 vials: 3000 units) once daily for 5 days, or
      until delivery, while 13 women ("controls") were treated with doses of AT
      sufficient to maintain at least 80% of the activity. High-dose therapy was
      associated with prolongation of pregnancy by 2.5 days more when compared with
      controls (p = 0.03; Mann-Whitney test). The incidence of clinical significant
      bleeding was lower in cases than in controls (mean 550 mL vs. 650 mL,
      respectively). Preventive- and conservative-type treatment of moderate-severe pre
      eclampsia, based on the administration high doses of AT, allows a significant
      prolongation of pregnancy, and thus a better neonatal outcome, as well as less
      maternal intra- and post-operative bleeding. Fn, PCR and elastase levels (markers
      of inflammation) decrease in the HD group in comparison with SD group. In the HD
      group, the AT plasma levels were obviously higher both at the end of the
      treatment (p < 0.0001) and after delivery (p = 0.03), in comparison with SD
      group. The fibrinogen and D-dimer levels were above the reference interval in
      both groups. TPA and PAI 1 were found to be significantly raised in the course of
      pre-eclampsia. In conclusion, the bio-chemical findings support a role for AT in
      controlling the haemostasis at conventional doses, and the inflammatory state at
      higher doses.

PMID- 14961156
TI  - Maternal thrombophilias are not associated with early pregnancy loss.
AB  - We investigated the association between inherited and acquired maternal
      thrombophilias and adverse pregnancy events. A cohort of 491 patients with a
      history of adverse pregnancy outcomes was evaluated for activated protein C
      resistance, factor V Leiden and prothrombin G20210A mutations,
      hyperhomocysteinemia, deficiencies of antithrombin, protein C and S and both
      anticardiolipin antibodies and lupus anticoagulants. The study had an 80% power
      to detect a 15% difference in the prevalence of thrombophilia for 1(st) trimester
      loss. In our high-risk cohort the presence of 1 maternal thrombophilia or more
      than one thrombophilia were found to be protective of recurrent losses at < 10
      weeks (1 thrombophilia: OR: 0.55, 95% CI: 0.33-0.92; > 1 thrombophilia: OR: 0.48,
      95%CI:0.29-0.78). In contrast, the presence of maternal thrombophilia(s) was
      modestly associated with an increased risk of losses > 10 weeks (1 thrombophilia:
      OR:1.76, 95%CI: 1.05-2.94, >1 thrombophilia: OR:1.66, 95%CI:1.03-2.68). Women who
      experienced only euploid losses were not more likely to have an identified
      thrombophilia than women who experienced only aneuploid losses (OR 1.03; 0.38
      2.75). The presence of maternal thrombophilia was associated with an increased
      risk of fetal loss after 14 weeks, fetal growth restriction, abruption and
      preeclampsia. There was a significant "dose-dependent" increase in the risk of
      abruption (OR:3.60, 95%CI: 1.43-9.09) and preeclampsia (OR:3.21, 95%CI:1.20
      8.58). In conclusion, these data indicate maternal thrombophilias are not
      associated with pregnancy wastage prior to 10 weeks of gestation.

PMID- 14961157
TI  - Effect of age on the performance of single detector helical computed tomography
      in suspected pulmonary embolism.
AB  - The prevalence of pulmonary embolism increases with age, but reduces the
      diagnostic yield of ventilation-perfusion lung scan age. Helical computed
      tomography (hCT) is widely used to diagnose pulmonary embolism, and should be
      less susceptible to the influence of age. We studied the influence of age on the
      performance of hCT to verify that hypothesis. We analyzed a database of 299
      consecutive outpatients suspected of pulmonary embolism, in whom pulmonary
      embolism was diagnosed according to accepted criteria, and who were all submitted
      to a helical CT. We divided the patient population into tertiles, corresponding
      to the following age categories: less than 59 years (group 1), 60 to 75 years
      (group 2), and over 75 years (group 3). Sensitivity and specificity of hCT were
      calculated in each age category. Overall sensitivity was 70% (95% CI: 62 to 78)
      and specificity was 91% (95% CI: 86 to 95). Sensitivity was 81% (95% CI: 64 to
      93) in group 1, 63% (95% CI: 46 to 78) in group 2, and 67 % (95% CI: 52 to 80) in
      group 3. The corresponding values for specificity were 92% (95% CI: 82 to 97) in
      group 1, 86% (95% CI: 75 to 94) in group 2 and 96% (95% CI: 87 to 100) in group
      3. Positive predictive values ranged from 75% to 94% and negative predictive
      values from 77% to 94%. Our data suggest that age does not have a marked
      influence on the diagnostic performances of hCT in clinically suspected pulmonary
      embolism.

PMID- 14961158
TI  - Local INR calibration of the Owren type prothrombin assay greatly improves the
      intra- and interlaboratory variation. A three-year follow-up from the Swedish
      national external quality assessment scheme.
AB  - In 1999, a simplified procedure for calibration of the Owren prothrombin time
      (Owren PT) assay was introduced by a working group of the organisation for
      national quality assurance in laboratory medicine in Sweden. The new protocol
      allowed local calibration by means of only two lyophilised national plasma
      calibrators and expression of results as an international normalized ratio (INR).
      This is our report of a three-year follow-up involving the analysis of data from
      all laboratories, in hospitals (n=88 in 2002) and primary health care units
      (n=246 in 2002) that perform the Owren PT assay in Sweden. The interlaboratory
      variation was significantly improved after the introduction of the new
      calibration procedure. For the larger hospital-based laboratories, the mean
      coefficient of variation (CV) was reduced from 7.9% to 5.2% (p<0.0001) when
      analysing test materials with INR range 2-4. In the higher INR range (>4), the CV
      was reduced even further, from 10.4% to 6.8% (p<0.0001). The corresponding
      results from smaller laboratories in the primary health care units showed a
      similar decrease in CV from 8.2% to 5.7% in the INR range 2-4 (p<0.0001). At the
      INR range >4, the CV was reduced from 9.5% to 7.8%. The intralaboratory variation
      was also improved for both types of laboratory categories. This study shows an
      improved precision, with CV less than 6% at the therapeutic INR range, for both
      hospital-based laboratories and smaller laboratories in the primary health care
      system. The results indicate that the Owren PT assay is well suited for local INR
      calibration employing only two calibrant plasmas in a simplified procedure.

PMID- 14961159
TI  - Increased fasting total homocysteine plasma levels as a risk factor for
      thromboembolism in children.
AB  - Elevated total homocysteine (tHcy) concentrations are an independent risk factor
      for thromboembolic events in adults. In children with moderate
      hyperhomocysteinemia data are sparse. Therefore, between 1995 and 2002 we
      consecutively recruited 163 white pediatric patients with a first symptomatic
      thromboembolic event and 255 healthy controls (mean age: 6.4 years in patients
      vs. 6.6 years in controls, range: 3 months to 18 years) and measured fasting tHcy
      levels. Median tHcy levels in patients were significantly higher (6.6 micromol/l,
      range 2.9-20.4 micromol/l) than in controls (5.7 micromol/l, 2.0-14.0 micromol/l,
      p<0.0001). 48 of the 163 patients with thromboembolism (29.5%) versus 26 of the
      255 controls (10.2%) had tHcy levels above the age-specific normal 90th
      percentile (OR 2.9, 95%CI: 1.7-4.8). The odds ratio for children in the highest
      quintile compared to children with levels in the lowest quintile was 4.3 (1.6
      8.1; highest quintile: median tHcy level 9.6 micromol, range 8.0-20.4), showing a
      significantly increased risk for thromboembolic disease with even mild
      hyperhomocysteinemia. We conclude that hyperhomocysteinemia above the age
      specific cut-off values is a risk factor for thromboembolic events in children.
      Therefore, screening for elevated fasting tHcy levels of patients with
      thromboembolism is recommended to stratify the risk of thromboembolism.

PMID- 14961160
TI  - Effects of a snake venom metalloproteinase, triflamp, on platelet aggregation,
      platelet-neutrophil and neutrophil-neutrophil interactions: involvement of
      platelet GPIbalpha and neutrophil PSGL-1.
AB  - The biologically active components from Viperidae venoms specifically affect cell
      matrix interactions, and have been utilized for developing anti-adhesive therapy
      as anti-thrombotic and anti-angiogenic agents. Utilizing platelet aggregometry
      coupled with flow cytometry, we found that a metalloproteinase isolated from
      Trimeresurus flavoviridis, termed triflamp, inhibited heterotypic adhesion
      between platelets and neutrophils in whole blood samples. Triflamp is a monomeric
      glycoprotein with a molecular weight of approximately 28 kDa. Triflamp has a N
      terminal amino acid sequence homologous to other venom metalloproteinases
      isolated from T. flavoviridis. The enzymatic activity of triflamp was inhibited
      by EDTA and phenanthroline but not by PMSF. Moreover, triflamp is a pure alpha
      fibrinogenase. Studies aimed at determining the nature of triflamp in affecting
      platelets or neutrophils revealed a selective inhibitory activity to glycoprotein
      (GP) Ibalpha-dependent platelet aggregation and PSGL-1-dependent neutrophil
      homotypic aggregation, indicating that its effects are rather specific. As judged
      by Western blotting, GPIbalpha on platelets and PSGL-1 on neutrophils are the
      substrates of triflamp. In conclusion, we suggest the novel role of venom
      metalloproteinase from Viperidae affecting the blood cell-cell interactions, thus
      offering a potential approach for further exploration of anti-inflammatory
      agents.

PMID- 14961161
TI  - Plasma membrane Ca(2+)-ATPase (PMCA) translocates to filopodia during platelet
      activation.
AB  - The plasma membrane Ca(2+)-ATPase (PMCA) plays an essential role in maintaining
      low cytosolic Ca2+ in platelets. Recently we demonstrated that PMCA is recruited
      to the cytoskeleton by interacting with PDZ domains. In the present study we
      determined the subcellular localization of PMCA using immunofluorescence
      microscopy. In resting platelets PMCA was distributed over the entire plasma
      membrane. Upon activation with thrombin, PMCA was found in filopodia adjacent to
      the actin cytoskeleton. PMCA translocation to filopodia was prevented by a
      peptide containing the last 10 residues of PMCA4b, the predominate isoform of
      PMCA in platelets, which contains a known PDZ domain-binding motif and was
      previously shown to block association of PMCA with the cytoskeleton.
      Incorporation of the PMCA C-terminal peptide did not affect the rate or extent of
      platelet aggregation, but significantly enhanced the rate of clot retraction.
      These results show that PMCA association with the cytoskeleton during platelet
      activation results in translocation of this Ca(2+)-pump to filopodia and that
      this association may affect later stages of platelet activation. The consequence
      of PMCA translocation to filopodia is likely a reduction in the local
      concentration of free Ca2+ in these structures resulting in regulation of the
      rate of clot retraction.

PMID- 14961162
TI  - Platelets in patients with acute ischemic stroke are exhausted and refractory to
      thrombin, due to cleavage of the seven-transmembrane thrombin receptor (PAR-1).
AB  - Platelet activation is involved in the pathogenesis of cerebrovascular ischemia,
      but the major agonist involved has yet to be identified. To investigate the role
      of thrombin in platelet activation in patients with acute ischemic stroke, and
      while thrombin is the most likely candidate for activation of the thrombin
      receptor PAR-1 in vivo, we assessed its cleavage and internalization using the
      antibodies SPAN12, binding to uncleaved PAR-1, and WEDE15, recognizing cleaved
      and uncleaved, but not internalized PAR-1. In contrast to healthy age-matched
      controls, platelets from stroke patients exhibited significant cleavage and
      internalization of PAR-1 (P<0.001) and failed to respond to thrombin in vitro.
      Enhanced surface expression of CD62P, CD63, TSP-1 and less mepacrine uptake
      showed platelet degranulation during stroke. Platelets from patients with acute
      cerebral ischemia are exhausted and desensitized to thrombin through cleavage of
      PAR-1, indicating that high concentrations of thrombin occur with acute
      cerebrovascular ischemic events in vivo.

PMID- 14961163
TI  - Sustained elevated amounts of circulating procoagulant membrane microparticles
      and soluble GPV after acute myocardial infarction in diabetes mellitus.
AB  - During myocardial infarction (MI), platelet activation and endothelial apoptosis
      are responsible for the release of procoagulant membrane-derived microparticles
      (MP) in the blood flow. MP prothrombotic and proinflammatory properties may be
      crucial for coronary prognosis. Elevated amounts of circulating procoagulant MP
      were described in diabetes mellitus (DM), and could be of particular significance
      in a MI context. We evaluated the prothrombotic status of DM and non-DM (NDM)
      patients at days 1 and 6 after MI, by measurement of circulating procoagulant MP
      and soluble GPV (sGPV), the platelet glycoprotein V major fragment released upon
      thrombin cleavage. Variations were compared to values measured in healthy
      volunteers (HV). Procoagulant MP were captured onto insolubilized annexin V and
      quantified by prothrombinase assay. Their cellular origin was assessed. With
      respect to HV, the levels of procoagulant MP detected at D1 and D6 were elevated
      in DM and NDM, MP being significantly higher in DM vs. NDM. The high amounts of
      platelet-derived MP and the correlation between procoagulant MP and sGPV, testify
      to the central role of thrombin-activated platelets during MI in both DM and NDM
      subsets. The release of platelet and endothelial cell-derived MP persisted at D6
      and was more important in DM, the associated prothrombotic risk being also
      reflected by higher levels of sGPV. The endothelial damage revealed by
      endothelial-derived MP was twice that observed in NDM patients. In DM patients
      presenting cardio-vascular events at 6 month follow-up, MP levels were
      significantly higher at D1 after MI than in those without complication (24.9 +/-
      4.8 vs. 12.3 +/- 2.7 nM PhtdSer, p = 0.02), suggesting a prognostic potential for
      MP.

PMID- 14961164
TI  - Influence of plasma and erythrocyte factors on red blood cell aggregation in
      survivors of acute myocardial infarction.
AB  - Increased erythrocyte aggregation (EA) has been observed in patients with
      ischaemic heart disease (IHD), although most of these studies have been performed
      in the acute phase when reactant proteins may account for this increase. Little
      is known about the role played by the erythrocyte itself in this aggregation
      process. To ascertain the contribution of both plasma and erythrocyte factors to
      EA in IHD, we investigated the following parameters in 78 survivors of acute
      myocardial infarction (AMI) and in a well-matched control group of 98 subjects:
      EA, glucose, total cholesterol (T-Chol), low-density lipoprotein-cholesterol (LDL
      Chol), high-density lipoprotein-cholesterol (HDL-Chol), triglycerides,
      apolipoproteins A(1) and B, protein and functional fibrinogen, plasma sialic
      acid, membrane sialic acid, and the cholesterol and phospholipid content of the
      erythrocyte membrane. AMI survivors showed higher glucose (p<0.001), a borderline
      increase in triglycerides (p = 0.043), and a statistical decrease in Apo A(1) (p=
      0.003) relative to controls. EA, functional fibrinogen, and plasma sialic acid
      were statistically higher in AMI survivors than in controls (p= 0.001; p<0.001;
      p= 0.011, respectively). Membrane sialic acid content was statistically lower in
      AMI patients than in controls (p= 0.026). No differences were observed in either
      membrane cholesterol or phospholipids. Multivariate logistic regression analysis,
      in which EA was dichotomized as higher or lower than 8.7, demonstrated that
      triglyceride levels higher than 175 mg/dL (OR= 7.7, p= 0.001) and functional
      fibrinogen levels higher than 320 mg/dL (OR= 3.7, p= 0.004) were independently
      associated with a greater risk of erythrocyte hyperaggregability. Our results
      suggest that plasma lipids, predominantly triglycerides, and fibrinogen may not
      only enhance the development of ischaemic events by their recognized atherogenic
      mechanisms, but also by increasing EA.

PMID- 14961165
TI  - Relationships between plasma adiponectin and blood cells, hepatopancreatic
      enzymes in women.
AB  - Adiponectin, which is secreted specifically from adipocyte, is thought to play a
      key role in the metabolic syndrome. We studied the associations of plasma
      adiponectin concentrations with blood cells and hepatopancreatic enzymes in 339
      women aged 54.0 +/- 0.8 (mean +/- SE) years. Plasma adiponectin before and after
      adjustment for body composition or calculated insulin resistance increased in
      slight anemic women (372.6 +/- 2.6 x 10(4)/mm3) compared with non-anemic subjects
      (471.1 +/- 1.7) (all p < 0.0001), and were inversely associated with red blood
      cells (RBC), hemoglobin, hematocrit, white blood cells and platelet values (p <
      0.0001-0.02), independent of age, diastolic blood pressure, body mass index,
      serum triglyceride, insulin resistance or blood urea nitrogen. Age and
      adiponectin/body fat mass (%) were negative, and blood pressure and insulin
      resistance were positive significant independent determinants of RBC in step-wise
      regression analysis. Moreover, adiponectin before and after adjustment were
      inversely associated with serum ALAT, gammaGTP and ChE, and positively with
      amylase levels (p < 0.0001-0.02). These results indicate the possibility that
      increased adiponectin may contribute to the suppressive bone marrow function in
      vivo. Combined with the leptin's data, adipocyte derived proteins were related to
      the hematopoiesis, therefore it has shown the possible existence of adipose
      tissue/ bone marrow function linkage more clearly. Furthermore, hepatopancreatic
      enzyme associations with this protein may indicate the possibility that
      adiponectin will regulate the hepatopancreatic function in health and disease.

PMID- 14961166
TI  - Effects of biological variations on platelet count in healthy subjects in China.
AB  - The effects of biological variations on platelet counts were investigated in 694
      healthy subjects aged 18 to 60 years living in three cities including Chengdu
      (Sichuan Province), Suzhou (Jiangsu Province) and Harbin (Heilongjang Province)
      in China. Platelet counts in healthy subjects were significantly lower in Chengdu
      (52-202 x 10(9)/L) and Suzhou (60-259 x 10(9)/L) than in Harbin (154-348 x
      10(9)/L) (p <0.0001), but the mean platelet volume (MPV) determined concurrently
      was negatively correlated with platelet count, the MPV values were significantly
      higher in Chengdu (11.8-15.6 fl) and Suzhou (10.9-15.8 fl) than in Harbin (9.5
      approximately 12.9 fl) (p < 0.0001). Platelet counts were significantly higher in
      summer (73-289 x 10(9)/L) than in winter (52-202 x 10(9)/L) (p <0.0001), but the
      MPV values were lower in summer (11.2-14.7 fl) than in winter (11.8-15.6 fl) (p
      <0.05) in Chengdu. Platelet associated immunoglobulin (PA-IgG) in Chengdu was
      revealed to be significantly higher in the low platelet count group (<150 x
      10(9)/L, 13.5 +/- 7.1 ng/10(7) PLT) than in the normal platelet count group (> or
      =150 x 10(9)/L, 8.3 +/- 2.7 ng/10(7) PLT) (p <0.0001). Similar results were
      observed in Suzhou for the reticulated platelet ratio, which was significantly
      higher in the low platelet count group (19.5 +/- 7.1%) than in the normal
      platelet count group (11.6 +/- 2.7%) (p <0.01). The bleeding time in Chengdu
      showed a significantly longer time in the low platelet count group (8.6 +/- 2.3
      min) than in the normal platelet count group (6.0 +/- 1.2 min)(p <0.01). With
      regard to the effects of lipids on platelet counts, the HDL values were
      significantly higher in the normal platelet count group (1.60 +/- 0.76 mmol/L)
      than the low platelet count group (1.23 +/- 0.31 mmol/L) (p <0.01); but no
      significant differences in cholesterol and triglycerides values between the
      normal and low platelet count groups (p >0.05) were recorded. These findings
      suggest that the platelet counts could be greatly influenced in healthy subjects
      by biological variations such as geographical, seasonal, and lipid variations.

PMID- 14961167
TI  - Beneficial effects of vitamins D and K on the elastic properties of the vessel
      wall in postmenopausal women: a follow-up study.
AB  - Matrix-Gla Protein (MGP) is a strong inhibitor of vascular calcification, the
      expression of which is vitamin D dependent. MGP contains five gamma
      carboxyglutamic acid (Gla)-residues which are formed in a vitamin K-dependent
      carboxylation step and which are essential for its function. Hence vascular
      vitamin K-deficiency will result in undercarboxylated, inactive MGP which is a
      potential risk factor for calcification. In the present study we describe the
      effects of vitamin K1 and D supplementation on vascular properties in
      postmenopausal women. In a randomized placebo-controlled intervention study, 181
      postmenopausal women were given either a placebo or a supplement containing
      minerals and vitamin D (MD-group), or the same supplement with vitamin K1 (MDK
      group). 150 participants completed the study and analysis was performed on 108
      participants. At baseline and after three years, vessel wall characteristics,
      including compliance coefficient (CC), distensibility coefficient (DC), intima
      media thickness (IMT) and the Young's Modulus (E) were measured to assess the
      effect of the supplements on the change of these parameters. The results showed
      that the elastic properties of the common carotid artery in the MDK-group
      remained unchanged over the three-year period, but decreased in the MD- and
      placebo-group. Comparing the MDK- and placebo-group, there were significant
      differences in decrease of DC (8.8%; p<0.05), CC (8.6%; p<0.05), and in increase
      of PP (6.3%; p<0.05) and E (13.2%, p<0.01). There were no significant differences
      between the MD-group and placebo. No significant differences were observed in the
      change of IMT between the three groups. It is concluded that a supplement
      containing vitamins K1 and D has a beneficial effect on the elastic properties of
      the arterial vessel wall.

PMID- 14961168
TI  - Myocardial damage, coagulation activity and the response to thrombin inhibition
      in unstable coronary artery disease.
AB  - Unstable coronary artery disease is in most cases associated with plaque rupture,
      activation of the coagulation system and subsequent intracoronary thrombus
      formation which may cause myocardial cell damage. The aim of the present analysis
      was to assess the relation between troponin T, markers of coagulation activity,
      i.e. prothrombin fragment 1+2, thrombin-antithrombin complex, soluble fibrin and
      D-dimer, and ischemic events, i.e. death, myocardial (re-)infarction or
      refractory angina. 320 patients with unstable coronary artery disease were
      randomized to 72 hours infusion with inogatran, a low molecular weight direct
      thrombin inhibitor, or unfractionated heparin. Patients with elevated troponin
      levels had higher levels of prothrombin fragment 1+2, soluble fibrin and D-dimer
      before, during, and at 24 hours after cessation of anticoagulant treatment. These
      troponin-positive patients tended to have worse short-term clinical outcome,
      without relation to markers of coagulation activity. Troponin-negative patients
      with unchanged or early increased thrombin generation during treatment had a
      cluster of ischemic events within 24 hours after cessation of the study drug. The
      30-day ischemic event rate was 19 % in troponin-negative patients with unchanged
      or early increased prothrombin fragment 1+2, and 5.7 % in patients with decreased
      prothrombin fragment 1+2, p=0.006, and similarly 15 % in troponin-negative
      patients with unchanged or early increased thrombin-antithrombin complex and 4.5
      % in patients with decreased thrombin-antithrombin complex, p=0.02. In
      conclusion, in unstable coronary artery disease a troponin elevation indicates
      higher risk and higher coagulation activity. However, among the troponin negative
      patients, with a lower risk and lower coagulation activity, a part of the
      patients seem to be non-responders to treatment with a thrombin inhibitor
      expressed as unchanged or raised coagulation activity and a raised risk of
      ischemic events early after cessation of treatment.

PMID- 14961169
TI  - Long term prognosis of patients with myocardial infarction and normal coronary
      angiography: impact of inherited coagulation disorders.
AB  - The prognosis of patients with myocardial infarction (MI) and normal coronary
      arteries (NCA) in the presence of an inherited coagulation disorder is unknown.
      The purpose of this study was to compare the clinical thrombosis outcome of
      patients with (GpI) or without (GpII), inherited coagulation disorders, who
      suffered from an acute MI with NCA. Eighty two consecutive patients (mean age 49
      +/- 15 years; 29 females) with MI, but NCA, were recruited. Twelve patients (15%)
      had an inherited coagulation disorder. GpI and GpII were statistically similar
      regarding age (45 +/- 11 vs 50 +/- 16 years-old), gender (33 vs. 36% female),
      tobacco consumption (50 vs. 53%), diabetes mellitus (8 vs. 10%), hypertension (25
      vs. 17%), obesity (8.3 vs. 14%), family history of coronary heart disease (33 vs.
      19%), hypercholesterolemia (50 vs. 21%; p =.08), left ventricular ejection
      fraction (58 +/- 13 vs. 61 +/- 13%) and spasm (8.3% vs. 17%). All patients were
      initially treated with antiplatelet agents with the exception of one (8%) in GpI,
      and 6 (9%) in GpII who were taking oral anticoagulant therapy (ns). The mean
      follow-up was 57 +/- 26 (range from 2-91 months). During the outcome, 12/78
      (15.4%) thrombosis events occurred, including venous thrombosis or pulmonary
      embolism (1/12 vs. 1/66), reinfarction (2/12 vs. 4/66), and stroke (2/12 vs.
      2/66), with two events in one patient (GpI). Kaplan-Meier event-free survival,
      with combined end-point, defined as venous thrombo-embolic event, reinfarction,
      or stroke differed between the two groups: 4/12 (33.3%) in GpI and 7/66 (10.6%)
      in Gp II (p <.02). Patients with MI, NCA and congenital coagulation disorder
      present a high risk of thrombosis recurrence under antiplatelet agent.

PMID- 14961170
TI  - Low-dose warfarin in atrial fibrillation leads to more thromboembolic events
      without reducing major bleeding when compared to adjusted-dose--a meta-analysis.
AB  - The use of warfarin with a range INR of 2.0-3.0 is recommended in prevention of
      stroke for nonvalvular atrial fibrillation (AF) patients, in particular those
      older than 75 years. The risk of bleeding that is associated with this range of
      INR has led to evaluate lower ranges (low-dose or fixed minidose) in terms of
      risks and benefits. A meta-analysis of all randomized controlled trials
      evaluating 'low-intensity' 'minidose' or 'low-dose anticoagulant' treatment for
      prevention of thromboembolic events in AF was conducted by two independent
      reviewers. Study quality was evaluated in a blinded fashion. Four original
      studies were retrieved. Outcome events were determined in various treatment
      groups: ischemic stroke, systemic embolism, thromboses (ischemic stroke, systemic
      embolism or myocardial infarction), vascular death, major hemorrhage and
      hemorrhagic death. Results obtained with a random effects model were expressed as
      a common relative risk. Adjusted-dose warfarin compared with lower dose warfarin
      (INR < or = 1.6) in 2108 randomised patients significantly reduced the risk of
      any thrombosis: Relative risk (RR): 0.50 (95% CI; 0.25 to 0.97). The RR was 0.46
      (95%CI; 0.2 to 1.07) for ischemic stroke. Inversely lower dose did not
      statistically decrease the risk for major hemorrhage compared to adjusted-dose:
      RR adjusted-dose vs lower dose: 1.23 (95% CI; 0.67-2.27). The RR was 0.97 (95 %
      CI 0.27-3.54) for hemorrhagic death. Our meta-analysis showed that adjusted-dose
      compared with low-dose or minidose warfarin therapy (INR < or =1.6) was more
      effective to prevent ischemic thromboembolic events in patients with atrial
      fibrillation.

PMID- 14961171
TI  - Metabolism of tumour-derived urokinase receptor and receptor fragments in cancer
      patients and xenografted mice.
AB  - The urokinase-type plasminogen activator receptor (uPAR) is involved in cell
      migration and tissue remodelling, as a receptor for pro-uPA, as a cell adhesion
      component, and in a soluble form as a chemoattractant.We have analyzed the
      presence and the molecular forms of uPAR and uPAR-fragments in urine of ovarian
      cancer patients in comparison with tumour tissue, ascites, and serum. Carcinoma
      tissue contained high levels of uPAR, but more abundantly the D2D3-fragment.
      Ascitic fluid contained similar ratio's of suPAR fragments as corresponding
      tumour tissue, but serum only contained intact suPAR. Interestingly, urine
      contained predominantly the uPAR-fragments D1 and D2D3, and the pattern of these
      fragments was different in cancer patients as compared to healthy individuals. To
      confirm the hypothesis that circulating and urinary suPAR and suPAR-fragments
      originate from the tumour tissue, the presence of human suPAR (fragments) was
      analyzed in mice xenografted with human tumours. Indeed, high levels of urinary
      D1 fragment were found in mice carrying a tumour displaying cleaved uPAR on the
      cell surface, but little or no D1 was found in the urine from mice carrying a
      tumour with full-length uPAR. Mouse serum contained only intact suPAR. Our data
      demonstrate that the enhanced levels of suPAR fragments in the urine of cancer
      patients is likely to originate from uPAR expressed in the tumour tissue.
      Considering the biological activities that uPAR fragments display, the level and
      typing of uPAR fragments in urine might therefore be clinically more relevant
      than the plain serum uPAR content.

PMID- 14961172
TI  - Characterisation of lymphocyte responses to Ca2+ in Scott syndrome.

PMID- 14961173
TI  - Once daily application of a combination of calcipotriol and betamethasone
      dipropionate (Dovobet, Daivobet) for the treatment of psoriasis.
AB  - This new compound product containing 50 micrograms/gram calcipotriol and 0.5
      milligrams/gram betamethasone dipropionate was recently introduced in Canada for
      the treatment of psoriasis. Clinical trials demonstrated that this compound was
      more active than either agent used alone. Recent changes in the product monograph
      involving the reduction in dose to once daily use has raised questions about the
      relevance of some previous comparisons of twice daily Dovobet. Pooling the
      available data from 5,500 patients in clinical trials for Dovobet will allow an
      inter-trial comparison of the various treatment arms, demonstrating that Dovobet,
      when applied once daily is significantly more effective than with twice daily
      applications of either its individual components used alone.

PMID- 14961174
TI  - Sequence variation in the ribosomal DNA internal transcribed spacer of Tridacna
      crocea.
AB  - DNA-based genetic markers are needed to augment existing allozyme markers in the
      assessment of genetic diversity of wild giant clam populations. The dearth of
      polymorphic mitochondrial DNA regions amplified from known universal polymerase
      chain reaction (PCR) primers has led us to search other regions of the genome for
      viable sources of DNA polymorphism. We have designed tridacnid-specific PCR
      primers for the amplification of internal transcribed spacer regions. Sequences
      of the first internal transcribed spacer segment (ITS-1) revealed very high
      polymorphism, showing 29% variation arising from base substitutions alone.
      Preliminary restriction analysis of the ITS regions using 8 restriction enzymes
      revealed cryptic changes in the DNA sequence. These mutations are promising as
      marker tools for differentiating geographically separated populations. Such
      variation in the ITS region can possibly be used for population genetic analysis.

PMID- 14961175
TI  - Pattern of inheritance of microsatellite loci in the squid Loligo pealeii
      (Mollusca: Cephalopoda).
AB  - Six microsatellite loci are described for the squid Loligo pealeii. All loci
      exhibit some degree of allelic diversity. The pattern of inheritance was tested
      for 3 loci through an analysis of the filial genotypes from a female-male mating.
      At all 3 loci, the ratios of the filial genotypes conformed to the ratios
      expected by Mendelian inheritance. The hypervariable loci will be useful in
      studies on sexual selection in this species, whereas the relatively less variable
      loci will be useful to address questions of population structure.

PMID- 14961176
TI  - Isolation and characterization of novel hydrocarbon-degrading euryhaline
      consortia from crude oil and mangrove sediments.
AB  - Two novel and versatile bacterial consortia were developed for the biodegradation
      of hydrocarbons. They were isolated from crude oil from the Cormorant Field in
      the North Sea (MPD-7) and from sediment associated with mangrove roots (MPD-M).
      The bacterial consortia were able to degrade both aliphatic and aromatic
      hydrocarbons in crude oils very effectively in seawater (35 g/L NaCl) and
      synthetic media containing 0 to 100 g/L NaCl (1.7 M). Salinities over twice that
      of normal seawater decreased the biodegradation rates. However, even at the
      highest salinity biodegradation was significant. Ratios of nC17 to pristane and
      nC18 to phytane were significantly lowered across the range of salinity. The
      lowest values were at 0 and 20 g/L (0.34 M). Phytane was degraded in preference
      to pristane. The degradation of these compounds was constant over the salinity
      range, with evidence of a slight increase for consortium MPD-M with increasing
      salinity. In general, the consortium isolated from mangrove root sediments was
      more efficient in metabolizing North Sea crude oil than the consortium isolated
      from Cormorant crude oil. The 5 strains that comprise MPD-M have been tentatively
      identified as species of the genera Marinobacter, Bacillus, and Erwinia. This is
      the first report of hydrocarbon-degrading consortia isolated from crude oil and
      mangrove sediments that are capable of treating oily wastes over such a wide
      range of salinity.

PMID- 14961177
TI  - A molecular biomarker system for assessing the health of coral (Montastraea
      faveolata) during heat stress.
AB  - Using a novel molecular biomaker system (MBS), we assessed the physiological
      status of coral (Montastraea faveolata) challenged by heat stress by assaying
      specific cellular and molecular parameters. This technology is particularly
      relevant for corals because heat stress is thought to be an essential component
      of coral bleaching. This phenomenon is widely believed to be responsible for
      coral mortality worldwide, particularly during 1997-1998. Specific parameters of
      coral cellular physiology were assayed using the MBS that are indicative of a
      nonstressed or stressed condition. The MBS distinguished the separate and
      combined effects of heat and light on the 2 coral symbionts, a scleractinian
      coral and a dinoflagellate algae (zooxanthellae). This technology aids in the
      accurate diagnosis of coral condition because each parameter is physiologically
      well understood. Finally, the MBS technology is relatively inexpensive, easy to
      implement, and precise, and it can be quickly adapted to a high-throughout
      robotic system for mass sample analysis.

PMID- 14961178
TI  - Expression of POU, Sox, and Pax genes in the brain ganglia of the tropical
      abalone Haliotis asinina.
AB  - In gastropod mollusks, neuroendocrine cells in the anterior ganglia have been
      shown to regulate growth and reproduction. As a first step toward understanding
      the molecular mechanisms underlying the regulation of these physiological
      processes in the tropical abalone Haliotis asinina, we have identified sets of
      POU, Sox, and Pax transcription factor genes that are expressed in these ganglia.
      Using highly degenerate oligonucleotide primers designed to anneal to conserved
      codons in each of these gene families, we have amplified by reverse transcriptase
      polymerase chain reaction 2 POU genes (HasPOU-III and HasPOU-IV), 2 Sox genes
      (HasSox-B and HasSox-C), and two Pax genes (HasPax-258 and HasPax-6). Analyses
      with gene-specific primers indicated that the 6 genes are expressed in the
      cerebral and pleuropedal ganglia of both reproductively active and spent adults,
      in a number of sensory structures, and in a subset of other adult tissues.

PMID- 14961179
TI  - Strategies for amplification by polymerase chain reaction of the complete
      sequence of the gene encoding nuclear large subunit ribosomal RNA in corals.
AB  - The nearly complete nuclear large subunit ribosomal RNA (LSU rRNA) gene in corals
      was amplified by primers designed from polymerase chain reaction (PCR)
      strategies. The motif of the putative 3'-terminus of the LSU rRNA gene was
      sequenced and identified from intergenic spacer (IGS) clones obtained by PCR
      using universal primers designed for corals. The 3'-end primer was constructed in
      tandem with the universal 5'-end primer for the LSU rRNA gene. PCR fragments of
      3500 bp were amplified for octocorals and non- Acropora scleractinian corals.
      More than 80% of the Acropora LSU rRNA gene (3000 bp) was successfully amplified
      by modification of the 5'-end of the IGS primer. Analysis of the 5'-end of LSU
      rDNA sequences, including the D1 and D2 divergent domains, indicates that the
      evolutionary rate of the LSU rDNA differs among these taxonomic groups of corals.
      The genus Acropora showed the highest divergence pattern in the LSU rRNA gene,
      and the presence of a long branch of the Acropora clade from the other
      scleractinian corals in the phylogenetic tree indicates that the evolutionary
      rate of Acropora LSU rDNA might have accelerated after divergence from the common
      ancestor of scleractinian corals.

PMID- 14961180
TI  - Genomic bacterial artificial chromosome library of the Japanese flounder
      Paralichthys olivaceus.
AB  - We have constructed a genomic bacterial artificial chromosome (BAC) library from
      homozygous cloned Japanese flounder Paralichthys olivaceus using the pBAC- lac
      vector. This BAC library consists of about 49,100 clones and is deposited in 128
      microtiter plates with 384 wells. The average size of inserted DNA was calculated
      to be 165 kb. The BAC library was determined to cover 9 times the Japanese
      flounder haploid genome. The Japanese flounder genomic BAC library will be useful
      for gene isolation as well as quantitative trait loci (QTL) analysis.

PMID- 14961181
TI  - Molecular cloning and antiserum development of cyclin box in the brown tide alga
      Aureococcus anophagefferens.
AB  - Cyclins can be useful cell cycle markers for growth rate studies on harmful algal
      blooms. In this study, a gene fragment corresponding to cyclin box was cloned for
      the brown tide alga Aureococcus anophagefferens. This algal gene fragment,
      designated as Btcycl1, was most similar to cyclin B. Oligopeptides based on the
      deduced amino acid sequence were synthesized and used to raise an antiserum that
      reacted on Western blots with a protein of about 63 kDa, the same size as cyclin
      B in other organisms. The cyclin B-like protein recognized by this antiserum, and
      the messenger RNA amplified using the primers, were more abundant in exponential
      cultures and decreased markedly in stationary cultures. This protein also
      appeared to be cell cycle dependent. Immunofluorescence labeling showed that this
      antiserum specifically stained a protein in Aureococcus cells and had no cross
      reaction with bacteria that were present in the algal culture. The Btcycl1
      sequence and the antiserum will provide a useful tool for studies on regulation
      of in situ growth rate for this brown tide alga.

PMID- 14961182
TI  - Microsatellite DNA population structure and stock identification of steelhead
      trout (Oncorhynchus mykiss) in the Nass and Skeena rivers in northern British
      Columbia.
AB  - Population structure and the application to genetic stock identification for
      steelhead (Oncorhynchus mykiss) in the Nass and Skeena Rivers in northern British
      Columbia was examined using microsatellite markers. Variation at 8 microsatellite
      loci (Oki200, Omy77, Ots1, Ots3, Ssa85, Ots100, Ots103, and Ots108) was surveyed
      for approximately 930 steelhead from 7 populations in the Skeena River drainage
      and 850 steelhead from 10 populations in the Nass River drainage, as well as 1550
      steelhead from test fisheries near the mouth of each river. Differentiation among
      populations within rivers accounted for about 1.9 times the variation observed
      among years within populations, with differences between drainages less than
      variation among populations within drainages. In the Nass River, winter-run
      populations formed a distinct group from the summer-run populations. Winter-run
      populations were not assessed in the Skeena River watershed. Simulated mixed
      stock samples suggested that variation at the 8 microsatellite loci surveyed
      should provide relatively accurate and precise estimates of stock composition for
      fishery management applications within drainages. In the Skeena River drainage in
      1998, Babine River (27%) and Bulkley drainage populations (31%) comprised the
      main components of the returns. For the Nass River in 1998 steelhead returning to
      Bell-Irving River were estimated to have comprised 39% of the fish sampled in the
      test fishery, with another 27% of the returns estimated to be derived from
      Cranberry River. The survey of microsatellite variation did not reveal enough
      differentiation between Nass River and Skeena River populations to be applied
      confidently in estimation of stock composition in marine fisheries at this time.

PMID- 14961183
TI  - Oxygen: at the foundation of wound healing--introduction.
AB  - "Wound Healing: Oxygen & Emerging Therapeutics" Columbus, Ohio, September 12-15,
      2002. Sponsored by the National Institutes of Health (R13 AR 049171),
      International Union of Biochemistry & Molecular Biology and UNESCO-Global Network
      of Molecular & Cell Biology. Conference co-chairs: Chandan K. Sen, the Ohio State
      University Medical Center and Thomas K. Hunt, University of California-San
      Francisco. This congress was conceived for two reasons: to consolidate what is
      known about oxygen in the repair process and to stimulate discussion about new
      developments of control of healing by redox regulated signaling processes. A
      historical and evolutionary perspective on the role of oxygen in wound healing-
      from the classical physiology of oxygen in the wound to the refined concept of
      redox signaling--is presented.

PMID- 14961184
TI  - Experimental models of stress and wound healing.
AB  - Experimental animal models have been used to examine stress-induced interactions
      among the nervous, endocrine, and immune systems. Generally, the response to
      stress results in a body-wide set of physiologic adaptations, mediated through
      the activation of neuroendocrine pathways that intersect and modulate
      inflammatory and immune responses. These interacting responses modulate diverse
      physiological processes including the initiation of tissue repair and wound
      healing. Two different stressors were used to activate neuroendocrine responses
      to study their impact on wound healing: restraint (RST) and social disruption
      (SDR). Previous studies showed that both stressors activate the hypothalamic
      pituitary-adrenal (HPA) axis, resulting in elevated plasma levels of the
      corticosterone (cort) response and modulation of pro-inflammatory cytokine
      response. To test the effects of stress-induced HPA activation on inflammatory
      responses and wound healing, a 3.5-mm cutaneous punch biopsy wound was placed on
      the dorsal surface of control and stressed (RST or SDR) C57BL/6 male mice and the
      kinetics of wound healing were studied over 10 days. RST slowed wound healing in
      inbred C57BL/6 mice, whereas the wounds on SDR mice healed in a fashion similar
      to the non-stressed, home cage controls.

PMID- 14961185
TI  - Reactive oxygen species and EGR-1 gene expression in surgical postoperative
      peritoneal adhesions.
AB  - Postoperative peritoneal adhesions are common and serious complications of
      general abdominal and gynecological surgery that can lead to chronic abdominal
      pain, small-bowel obstruction and infertility. The specific pathophysiology of
      peritoneal adhesions remains elusive and current treatment is relegated to
      prevention through meticulous surgical technique and protective physical
      barriers, gels and solutions. We have reported that reactive oxygen species
      (ROS), generated by phagocytic cells at the site of tissue injury, serve as major
      signaling molecules regulating the expression of vascular endothelial growth
      factor (VEGF) and subsequent wound repair. We hypothesized that peritoneal
      adhesions are a product of over-healing surgical wounds and that, like in wound
      healing, ROS are implicated in their pathogenesis. We examined the presence of
      footprints of ROS and the ROS-inducible angiogenic factor VEGF in human adhesion
      tissue. An experimental model of peritoneal adhesion was established in rodents
      to study of the dynamics of ROS-induced gene expression during de novo adhesion
      tissue formation. Immunohistochemical analysis demonstrated presence of
      ROS/oxidant and macrophages in human peritoneal tissue. The presence of ROS and
      ROS-sensitive transcription factor EGR-1 was also evident in an experimental
      rodent peritoneal adhesion model. Along with ROS, VEGF, and a large number of
      mature and immature CD31/vWF positive blood vessels were present in the adhesion
      tissue. These observations are not consistent with the contention that adhesions
      are non-functional scar tissue. The newly developed rodent model of adhesion may
      present a useful approach to reproducibly and objectively study molecular
      mechanisms underlying the dynamic process of de novo adhesion tissue formation.

PMID- 14961186
TI  - Development of a wound dressing targeting neutrophil function.
AB  - Earlier studies show that neutrophils are virtually unable to kill Staphylococcus
      aureus in vitro. However, upon addition of 10 mM N-acetylcysteine (NAC) or
      reduced glutathione (GSH) the neutrophil bacterial killing ability becomes
      excellent. We want to exploit this phenomenon to develop a wound dressing
      material that will improve neutrophil function. To study the mechanisms behind
      the downregulation of neutrophil elimination of bacteria, we used different
      markers for neutrophil function on surface-adhering neutrophils in contact with
      S. aureus with or without addition of the antioxidants NAC or GSH. Analysis by
      scanning electron microscopy showed cell shrinkage and numerous cytoplasmic
      processes on surface-adhering neutrophils exposed to S. aureus. In cells exposed
      to S. aureus and GSH, the cells were of normal size and the cytoplasm was spread
      as in normal attachment. Staining for intracellular GSH, a hallmark of oxidative
      stress, showed little difference between the experimental groups, indicating that
      the cells were not damaged by traditional oxidative stress. The H(2)O(2)
      production of neutrophils, measured by Amplex red, was correlated to bacterial
      exposure and was not affected by the addition of scavengers. The intracellular
      and extracellular production of ROS was measured by luminol-amplified
      chemiluminescence. The apparent ROS-production was mostly intracellular and
      decreased in the presence of scavengers. However, extracellular production of ROS
      was not affected by the addition of NAC. The production of nitric oxide (NO) was
      measured spectrophotometrically as the production of nitrate apparently decreased
      in the presence of scavengers, probably as a result of interference with the
      reagents in the test system. In conclusion, differences between leukocytes that
      were able to eliminate S. aureus and those that were not were mainly seen in the
      morphology of the cells and in cell viability. The morphological findings point
      to a difference in NO signaling in the absence and presence of ROS scavengers.

PMID- 14961187
TI  - Clinical hyperbaric oxygen therapy, wound perfusion, and transcutaneous oximetry.
AB  - Hyperbaric oxygen therapy (HBOT) is an important adjunct in the management of
      problem wounds which exist in chronic oxygen deficiency and in which the local
      oxygen tension is below optimal for healing. In the treatment of hypoxic and
      ischemic wounds, the most important effects of hyperbaric oxygenation are the
      stimulation of fibroblast proliferation and differentiation, increased collagen
      formation and cross-linking, augmented neovascularization, and the stimulation of
      leukocyte microbial killing. Ischemic soft tissues also benefit from
      hyperoxygenation through improved preservation of energy metabolism and reduction
      of edema. Hyperbaric oxygen is administered in either a multiplace or a monoplace
      hyperbaric chamber. Normally, pressures of 2 to 2.5 ATA are used for a period of
      90 minutes once or twice daily. For an objective assessment of wound perfusion
      and oxygenation, transcutaneous oximetry provides a simple, reliable,
      noninvasive, diagnostic technique. It can be used for assessment of tissue
      perfusion in the vicinity of the problem wound. Transcutaneous oximetry may be
      used in the assessment of wound healing potential, selection of amputation level,
      and patient selection for HBOT. In diabetic patients with chronic foot ulcers
      peri-wound transcutaneous oxygen tensions (TcP(O2)) over 400 mmHg in 2.5 ATA
      hyperbaric oxygen or over 50 mmHg in normobaric pure oxygen predict healing
      success with adjuncted HBOT with high accuracy.

PMID- 14961188
TI  - Oxygen in wound healing--more than a nutrient.
AB  - This article provides an overview of the role of oxygen in wound healing. The
      understanding of this role has undergone a major evolution from its long
      recognized importance as an essential factor for oxidative metabolism, to its
      recognition as an important cell signal interacting with growth factors and other
      signals to regulate signal transduction pathways. Our laboratory has been engaged
      in the study of animal models of skin ischemia to explore in vivo the impact of
      hypoxia as well as the use of oxygen as a therapeutic agent either alone or in
      combination with other agents such as growth factors. We have demonstrated a
      synergistic effect of systemic hyperbaric oxygen and growth factors that has been
      substantiated by Hunt's group. Within the past 10 years research in the field of
      wound healing has given new insight into the mechanism of action of hypoxia and
      hyperoxia as modifiers of the normal time-course of wound healing. The article
      concludes with a discussion of why hypoxia and hyperoxia intercurrently play an
      important role in wound healing. Hypoxia-inducible factor 1 is crucial in that
      interplay.

PMID- 14961189
TI  - Redox processes underlying the vascular repair reaction.
AB  - Accumulating evidence indicates that vascular dysfunction in atherosclerosis,
      hypertension, and diabetes is either caused by or accompanied by oxidative stress
      in the vessel wall. In particular, the role of redox processes as mediators of
      vascular repair and contributors to post-angioplasty restenosis is increasingly
      evident. Yet the pathophysiology of such complex phenomena is still unclear.
      After vascular injury, activation of enzymes such as NADPH oxidase leads to a
      marked increase in superoxide generation, proportional to the degree of injury,
      which rapidly subsides. Such early superoxide production is significantly greater
      after stent deployment, as compared to balloon injury. Recent data suggest the
      persistence of low levels of oxidant stress during the vascular repair reaction
      in neointimal and medial layers. Despite the compensatory increase in expression
      of iNOS and nNOS, nitric oxide bioavailability is reduced because of increased
      reaction rates with superoxide, yielding as by-products reactive nitrogen/oxygen
      species that induce protein nitration. Concurrently, the activity of vascular
      superoxide dismutases exhibits a sustained decrease following injury. This
      decreased activity appears to be a key contributor to vasoconstrictive remodeling
      and a major determinant of the occurrence of nitrative/oxidative stress.
      Replenishment of superoxide dismutase (SOD), as well as treatment with vitamins C
      and E or the lipid-lowering drug probucol and its analogs, led to decrease in
      constrictive remodeling and improved vessel caliber. Better understanding of the
      redox pathophysiology of vascular repair should help clarify the pathogenesis of
      many other vascular conditions and may provide novel therapeutic strategies to
      prevent vascular lumen loss.

PMID- 14961190
TI  - Oxygen in wound healing and infection.
AB  - It is a fundamental clinical observation that wounds do not heal in tissue that
      does not bleed, and they almost always heal in tissue that bleeds extensively.
      Continuous supply of oxygen to the tissue through microcirculation is vital for
      the healing process and for resistance to infection. Evaluation of tissue
      perfusion and oxygenation is important in all types of wound patients. Monitoring
      systems should measure the hemodynamic situation and the ability of the
      cardiovascular system to deliver an adequate volume of oxygen to meet the
      metabolic demands of the peripheral tissue. Oxygen therapy is important in
      relation to both healing and resistance to infections. External factors have been
      shown to significantly decrease the peripheral oxygen supply, and supplementary
      perioperative oxygen to reduce the surgical wound infection rate by one- half in
      patients undergoing colorectal resection. Hyperbaric oxygen therapy may be
      beneficial in situations where the nutritive flow and oxygen supply to the
      healing tissue are compromised by local injury, and particularly if anaerobic
      infection is present. However, the definitive proof for the effect and
      indications of this therapy in wound healing still has to be established. It can
      be concluded that adequate delivery of oxygen to the wound tissue is vital for
      optimal healing and resistance to infection. Assessment of perfusion and
      oxygenation is essential for the wound patient, as well as the treating
      personnel. The indication for hyperbaric oxygen treatment still needs to be
      defined. During wound healing the continuity and function of the damaged tissue
      are re-established. This is only possible through a restoration of the
      microcirculation and thereby the nutrition to the tissue. The main component of
      the nutrition is oxygen, which is critically important for healing a wound by
      production of granulation tissue and for ensuring resistance against infection.
      This has been shown experimentally, but recently a short period of supplementary
      oxygen has been shown to decrease wound complications in clinical practice as
      well.

PMID- 14961191
TI  - Aging and wound healing.
AB  - Impaired wound healing in the elderly presents a major clinical and economic
      problem. With the aging population growing in both number and percentage, the
      importance of understanding the mechanisms underlying age-related impairments in
      healing is increased. Normal skin exhibits characteristic changes with age that
      have implications for wound healing. Additionally, the process of wound healing
      is altered in aged individuals. Although historically healing in the aged was
      considered defective, there is now consensus that healing in the elderly is
      delayed but the final result is qualitatively similar to that in young subjects.

PMID- 14961192
TI  - Nitric oxide and wound healing.
AB  - Nitric oxide is a short-lived free radical that acts at the molecular, cellular,
      and physiologic level. Since its discovery almost 20 years ago it has proven
      itself as an important element in wound healing. This review highlights many of
      the important aspects of nitric oxide in wound healing, including a review of the
      basic biology of nitric oxide, its role as part of the cytokine cascade and as a
      promoter of angiogenesis, as well as its more recently elucidated role in
      apoptosis.

PMID- 14961193
TI  - Problems and prospects of managing thoracic aortic aneurysm at the Nnamdi Azikiwe
      University Teaching Hospital, Nnewi, Nigeria.
AB  - The objective of this report is to highlight the problems encountered in managing
      thoracic aortic aneurysm in a third-generation teaching hospital serving a purely
      rural community in the heartland of Anambra State, in the southeastern part of
      Nigeria. This report also proffers solutions aimed at assisting in providing
      better care for patients afflicted with this condition. From time to time,
      patients present with vascular diseases, including aneurysm, but the condition is
      only occasionally suspected and sparingly investigated. This is a report of two
      cases within the setting of the Nnamdi Azikiwe University Teaching Hospital
      (NAUTH), Nnewi Nigeria. After the death of these two patients, one of whom was a
      member of the staff of the hospital, post mortem examinations revealed that they
      had died of ruptured thoracic aortic aneurysm. Their medical records were
      retrieved from the Medical Records Department and reviewed with the aim of
      analyzing their clinical features and management in the light of the unexpected
      post-mortem examination results. The survey of the patient records revealed that
      the diagnosis of thoracic aortic aneurysm was not suspected in either patient
      even though both had symptoms pointing to this condition. The staff member was a
      55-year old man and the other patient was a 31-year old woman in her 30th week of
      pregnancy. We conclude by drawing the attention of medical practitioners in our
      community to the fact that thoracic aortic aneurysms are probably more common
      than we thought. Only a high index of suspicion will lead to clinical diagnosis
      and treatment.

PMID- 14961194
TI  - Prognostic significance of apex axillary invasion for locoregional recurrence and
      effect of postmastectomy radiotherapy on overall survival in node-positive breast
      cancer patients.
AB  - Postmastectomy irradiation substantially reduces the risk of locoregional
      recurrences (LRR) of breast carcinoma. However, debates continue on the
      prognostic factors for radiotherapy and the effect of radiotherapy on overall
      survival. The present study was undertaken to investigate the prognostic
      significance of level III positive nodes, along with the other factors for LRR,
      and to evaluate the effect of postmastectomy radiotherapy on overall survival
      among node-positive breast carcinoma treated systemically. Data from 549
      consecutive node-positive breast cancer patients who underwent modified radical
      mastectomy and received adjuvant systemic therapy were studied retrospectively.
      Prognostic factors for LRR and the effect of postmastectomy radiotherapy on
      overall survival were analyzed. Survival curves were generated by the Kaplan
      Meier method, and multivariate analysis was performed by the Cox proportional
      hazard model. The 5-year locoregional recurrence rate is 7%. Apical invasion was
      found to be an independent prognostic factor for LRR (HR 2.6, CI 1.29-5.35) along
      with a finding of 4 or more positive nodes and T3 tumor. Adjuvant radiotherapy
      decreased LRR and improved survival significantly. Apical invasion, 4 or more
      positive axillary lymph nodes, and T3 tumor are the predictors of LRR, and
      patients with these adverse factors are candidates for adjuvant radiotherapy.
      Postmastectomy radiotherapy improves overall survival.

PMID- 14961195
TI  - Obstructive jaundice in rats: cause of spatial memory deficits with recovery
      after biliary decompression.
AB  - Children with end-stage liver disease have been found to have cognitive deficits.
      The aim of this study was to examine whether cholestatic jaundice causes spatial
      deficits in rats and if these cognitive deficits are reversed by biliary
      drainage. Rats were randomly divided into three groups. In the first group, the
      bile duct was ligated for 3 weeks (BDL group); in the second group, the proximal
      bile duct was ligated with a Broviac CV catheter for 2 weeks followed by a tube
      bilioduodenostomy (TBD group); in the third group, a sham operation was performed
      (SHAM group). All the surviving rats were assessed for spatial learning and
      memory (a major cognitive function in rats) by the Morris water maze task about 3
      weeks after the first operation. Blood was aspirated by cardiocentesis and
      assayed for total bilirubin, albumin, ammonia, and hemoglobin levels on the day
      following the water maze task. During the four consecutive acquisition trial days
      of the Morris water maze, jaundiced rats (BDL group) had a significant longer
      latency to escape than the SHAM group ( p < 0.05). Rats that underwent biliary
      decompression for 1 week (TBD group) showed improved status of the spatial
      deficit, as they required less time to reach the escape platform, approaching the
      performance of the SHAM group. The BDL group had a significantly higher serum
      ammonia level, higher bilirubin level, and lower hemoglobin level than the other
      two groups. After biliary decompression for 1 week, the serum albumin
      concentration in the TBD group still did not return to the level of the SHAM
      group. The results of this study suggest that long-term cholestasis results in
      spatial memory deficits in rats that correlate with anemia and hyperbilirubinemia
      encephalopathy. Early biliary decompression of obstructive jaundice improves
      spatial memory deficits, possibly related to the recovery of the serum ammonia
      and hemoglobin levels.

PMID- 14961196
TI  - Surgical site infections in breast surgery: case-control study.
AB  - The purpose of this study was to estimate the frequency of surgical site
      infections (SSIs) and identify associated risk factors for each type of breast
      surgery at a cancer hospital. We used a nested case-control design. Between
      February 1, 2000 and July 31, 2000, all breast surgeries performed were recorded
      on a daily basis. After hospital discharge, we evaluated patients simultaneously
      with surgeons three times a week for 30 days or longer. The odds ratio (OR) was
      estimated using logistic regression analysis. The study followed 280 patients
      (298 wounds). Altogether, 77 SSIs were detected, for an overall SSI rate of 25.8%
      (77/298). For excisions, conservative surgery, and radical mastectomies the SSI
      rates were 1.4%, 18.0%, and 38.3%, respectively. Excisions were excluded ( n =
      68) for risk factor analysis. After multivariate analysis, risk factors
      associated with SSIs were obesity [OR 2.5, 95% confidence interval (CI) 1.2-4.3],
      concomitant chemotherapy and radiation (OR 2.3, 95% CI 1.2-4.3), radical surgery
      (OR 3.1, 95% CI 1.1-8.6), insertion of a second drain during the late
      postoperative period (OR 3.7, 95% CI 1.8-7.8), and drainage duration > or = 19
      days (OR 2.9, 95% CI 1.5-5.6). The bacteria most frequently isolated were
      Pseudomonas aeruginosa ( n = 18 ), Serratia sp. ( n = 18), Staphylococcus aureus
      ( n = 10), and Staphylococcus epidermidis ( n = 10). Poor compliance with
      infection control practices and wound management was detected throughout the
      study period. The overall frequency of SSIs for mastectomies was higher than the
      reported rates, which was principally related to the more radical surgery
      required for advanced-stage disease, preoperative irradiation, and inadequate
      wound and drain care.

PMID- 14961197
TI  - Evaluation of 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography for
      gastric cancer.
AB  - Positron emission tomography (PET) with (18)F-2-deoxy-2-fluoro-D-glucose (FDG)
      has been investigated as a means of detecting certain primary tumors and their
      metastatic disease in recent years. The aim of this study was to compare the
      performance of FDG-PET and operative assessment with formal pathologic staging.
      Altogether, 85 patients had undergone surgical treatment for gastric cancer with
      curative intent, with FDG-PET preoperatively. The results using FDG-PET were
      compared with those using computed tomography (CT); they were also correlated
      with the pathologic findings. For quantitative analysis, the regional tumor
      uptake was measured by the standard uptake value (SUV) using a region of interest
      technique. Using FDG-PET, the primary tumor was visualized in 75.2% of patients.
      A comparison of the FDG uptake and the clinicopathologic findings showed that
      there was a significant association between FDG uptake and the depth of invasion,
      the size of the tumor, and lymph node metastasis. FDG-PET scans had less accuracy
      for diagnosing locoregional lymph nodes than CT because of a significant lack of
      sensitivity (23.3% vs. 65.0%). The survival rate for patients with high FDG
      uptake (SUV > 4) was significantly lower than that for those with low FDG uptake
      (SUV < 4) ( p < 0.05). FDG-PET was successful in detecting the primary gastric
      cancer lesion but not for finding early-stage gastric cancers. Detection of nodal
      metastasis also was not possible by FDG-PET. However, FDG-PET appears to provide
      important additional information concerning the aggressiveness of the tumor and
      the prognosis in patients with gastric cancer.

PMID- 14961198
TI  - Deterioration of hepatic functional reserve in patients with hepatocellular
      carcinoma after resection: incidence, risk factors, and association with
      intrahepatic tumor recurrence.
AB  - Hepatocellular carcinoma (HCC) is frequently associated with liver cirrhosis.
      Patients with HCCs undergoing surgical resection may have declining hepatic
      functional reserve over time. However, the incidence and risk factors of hepatic
      decompensation, and its relation to postoperative tumor recurrence are unknown.
      This study investigated 241 HCC patients (208 male; age 61 +/- 13 years)
      undergoing resection with a long-term follow-up. The Child-Pugh scoring system
      was used to evaluate the postoperative deterioration of liver reserve, defined as
      a sustained increment in the Child-Pugh score by 2 or more. The 1-, 3-, and 5
      year cumulative probabilities of postoperative decompensation were 14%, 32%, and
      56%, respectively, during a follow-up period of 27 +/- 18 months (range 3-75
      months). The average increment in Child-Pugh score was 1.4 +/- 1.1 in 2.3 +/- 1.5
      years, or 0.6 point per year. Altogether, 74 (31%) patients developed
      postoperative hepatic decompensation during the follow-up period, 43 (58%) of
      whom had decompensation within 2 years of resection. Large (> 3 cm) tumor size
      was the only independent predictor associated with hepatic decompensation
      (relative risk 1.7, 95% confidence interval 1.1-2.8, p = 0.041) and was a
      significant risk factor for intrahepatic tumor recurrence ( p = 0.018). Patients
      with tumor recurrence more frequently (40% of 109 patients vs. 23% of 132
      patients, p = 0.005) and more rapidly (0.8 vs. 0.4 point per year) developed
      hepatic decompensation than those without recurrence. In conclusion, large HCCs
      are closely associated with hepatic decompensation in patients after resection.
      Tumor recurrence may predispose to the development of hepatic decompensation in
      these patients.

PMID- 14961199
TI  - Xanthogranulomatous cholecystitis: 15 years' experience.
AB  - The demographic and clinical aspects of xanthogranulomatous cholecystitis (XGC)
      over a period of 15 years are reviewed. The review entailed examining 12,426
      clinical files of patients who had undergone cholecystectomy, including 182
      patients with a histopathologic diagnosis of XGC. Altogether, 1.46% of the
      cholecystectomies performed were done on patients with a diagnosis of XGC. XGC
      presented in patients over the age of 32, with a male/female ratio of 2:1.
      Thickening of the gallbladder wall, seen on ultrasonography and computed
      tomography scans, was demonstrated in 100% of the cases. A total of 17% of the
      cases presented in acute form. Obstructive jaundice was observed in 23% of the
      patients, 11 of which cases were associated with choledocholithiasis (30% of
      these patients had jaundice) and the rest with extrinsic obstruction of the bile
      tract (Mirizzi syndrome). XGC was associated with lithiasis in 85% of the cases.
      A malignant lesion was suspected during operation in 30% of the cases, requiring
      histopathologic examination during surgery. Carcinomatous lesions were found in
      3% of the cases. Surgical difficulty was reported in 65% of the cases, resulting
      in the performance of partial cholecystectomy in 35%. XGC is an infrequent form
      of chronic inflammation of the gallbladder, the clinical presentation of which is
      similar to that of cholecystitis; given the thickening of the gallbladder wall,
      it makes cholecystectomy difficult. As XGC may resemble adenocarcinoma,
      differentiation is essential by means of intraoperative histologic examination to
      ensure optimal surgical treatment.

PMID- 14961201
TI  - Dedicated screening mammography for diagnosis of small breast cancer.
AB  - Breast cancer is the most common malignancy in women, and early diagnosis is a
      cornerstone of successful treatment. Mammography is the sole acceptable method
      for breast cancer screening, but its efficacy is still disputable. The aim of
      this study was to determine whether the influence of dedicated mammographic team
      skills could improve the diagnostic accuracy of screening mammography and
      detection of small breast cancers. From June 1992 to September 1996 a total of
      17,393 screening mammograms and 335 mammographically guided needle-localization
      breast biopsies were performed. From August 1994, a dedicated mammographer
      commenced work in our hospital. Screening mammography and biopsy results were
      compared for the nondedicated period (NDP) and the dedicated period (DP). The
      biopsy rate decreased from 2.9% to 1.3% (p < 0.0001), and the positive biopsy
      rate increased from 26.3% to 48.2% (p < 0.0001) during the respective periods.
      The cancer detection rate not changed significantly (p = 0.27) through the whole
      study period, but the subgroup of small carcinomas (T0, T1a, T1b) increased
      significantly (p < 0.04), from 25 cases in the NDP to 40 cases in the DP. We
      concluded that dedicated mammography team skills can significantly improve the
      detection of small breast cancers and permit more effective diagnosis of breast
      cancer by reducing the number of breast biopsies ultimately found to be benign.

PMID- 14961200
TI  - Metastatic tumor doubling time: most important prehepatectomy predictor of
      survival and nonrecurrence of hepatic colorectal cancer metastasis.
AB  - We determined the relative value of the metastatic colorectal cancer doubling
      time as a predictor of recurrence and survival after hepatectomy in comparison
      with other established predictors. Consecutive patients who underwent hepatic
      resection ( n = 144) for colorectal cancer liver metastases were studied
      retrospectively to identify factors that influence overall survival and
      recurrence in the remnant liver. Overall 5-year survival and nonrecurrence rates
      were 49.8% and 50.8%, respectively. By multivariate analysis, large liver tumors
      ( p = 0.038), p53 expression by the liver tumor (p = 0.011), and a short liver
      metastasis doubling time (< or = 45 days, p = 0.013) negatively affected
      survival; doubling times > 45 days (adjusted relative risk 0.06; p < 0.001)
      positively influenced disease-free survival. In patients with remnant liver
      recurrence, a short doubling time was associated with short disease-free
      intervals (7.3 +/- 6.2 months), multiple metastases (63.6%), and fewer attempts
      at repeat hepatectomy (22.7%). The doubling time determines tumor size and
      reflects the patient's immune and nutritional status. A short doubling time is
      the most reliable risk factor for multiple metastases, early recurrence, and poor
      prognosis. Further studies with a larger number of patients are needed to confirm
      this conclusion.

PMID- 14961202
TI  - Changes in extrathymic T cells in the liver and intestinal intraepithelium in
      mice with obstructive jaundice.
AB  - Recently, T cells were classified into two categories: intrathymic T cells (ITCs;
      thymus-derived T cells) and extrathymic T cells (ETCs). ETC, localized in the
      liver and intestinal intraepithelium (IE), play an important immunologic role in
      the suppressed condition of T-cell development in the thymus. Given the fact that
      complications of surgery in patients with obstructive jaundice are often related
      to immunosuppression in the gut-liver circulation, we attempted to investigate
      the changes in the proportion of ETCs in mice with obstructive jaundice. Three
      mice models were prepared ( n = 10 per group): sham group with simple laparotomy;
      ligation group with common bile duct ligation; deoxycholic acid (DCA) group with
      an oral intake of DCA as a model of the presence of bile salts in the gut lumen.
      In each model, total mononuclear cells (MNCs), ITCs in the thymus, and ETCs in
      the liver and IE were counted using monoclonal antibodies in conjunction with a
      two-color immunofluorescence test by flow cytometry. In the ligation group the
      number of MNCs was reduced in the thymus and IE, and only those in the IE
      recovered after oral intake of DCA. A decrease of ITCs in the thymus and the
      increase in ETCs in the liver and IE occurred simultaneously during the early
      phase of biliary obstruction. At day 7 after biliary obstruction, ETCs in the
      livers of the DCA and ligation groups decreased to nearly the level in the sham
      group. However, on day 7 the ETCs in the IE remained significantly higher in the
      DCA group than in the ligation group. These results suggested that ETCs can act
      in place of ITCs at an early phase of obstructive jaundice, and the presence of
      bile in the gut lumen may be associated with the consumption of ETCs in the IE, a
      reaction that may bring about improved immunoreactivity.

PMID- 14961203
TI  - Surgical treatment of Barrett's esophagus: 1980-2003.
AB  - Barrett's esophagus is a complication of long-standing gastroesophageal reflux
      and can be a premalignant condition. The goals of surgical treatment, which were
      well summarized by DeMeester, have been increased and more detailed by us. They
      consist of (1) controlling symptoms of gastroesophageal reflux disease; (2)
      abolishing acid and duodenal reflux into the esophagus; (3) preventing or
      eliminating the development of complications; (4) preventing extension of or an
      increase in the length of intestinal metaplasia; (5) inducing regression of
      intestinal metaplasia to the cardiac mucosa; and (6) preventing progression to
      dysplasia, thereby inducing regression of low-grade dysplasia and avoiding the
      appearance of an adenocarcinoma. We have reviewed 25 articles in the English
      language literature published from 1980 to 2003 dealing specifically with the
      surgical treatment of Barrett's esophagus. In most of these papers too few
      patients were included, the follow-up was less than 60 months, and the clinical
      success deteriorated with time. Acid reflux persists after surgery in nearly 35%
      of Barrett's esophagus patients; and at 10 years after surgery duodenal reflux is
      present in 95%. Peptic ulcer, stricture, and erosive esophagitis are present in
      15% to 30% late after surgery, and in 16% there is progression of the intestinal
      metaplasia. There is the appearance of low-grade dysplasia in 6.0% and
      adenocarcinoma in 3.4%, and there is regression of low-grade dysplasia in 45.0%.
      These results challenge the arguments supporting antireflux surgery for patients
      with Barrett's esophagus: The clinical results are not optimal, no long-lasting
      effect has been demonstrated, and it does not prevent the appearance of dysplasia
      or adenocarcinoma. An excellent alternative is acid suppression and a duodenal
      diversion procedure, which has had 91% clinical success for more than 5 years.
      This regimen has almost eliminated acid and duodenal reflux, and there has been
      no progression to dysplasia or adenocarcinoma. Moreover, in 60% of the patients
      with low-grade dysplasia, regression to nondysplastic mucosa has occurred.

PMID- 14961204
TI  - Complications of thyroid surgery: analysis of a multicentric study on 14,934
      patients operated on in Italy over 5 years.
AB  - Complication rates associated with thyroid surgery can be evaluated only through
      analysis of case studies and follow-up data. This study covers postoperative data
      from 14,934 patients subjected to a follow-up of 5 years. Among them, 3130
      (20.9%) underwent total lobectomy (TL), 9599 (64.3%) total thyroidectomy (TT),
      1448 (9.7%) subtotal thyroidectomy with a monolateral remnant (MRST), and 757
      (5.1%) subtotal thyroidectomy with bilateral remnants (BRST). A total of 6% of
      the patients had already been operated on. Persistent hypoparathyroidism occurred
      after 1.7% of all the operations, and temporary hypoparathyroidism was noted in
      8.3%. Permanent palsy of the laryngeal recurrent nerve (LRN) occurred in 1.0% of
      patients, transient palsy in 2.0%, and diplegia in 0.4%. The superior laryngeal
      nerve was damaged in 3.7%; dysphagia occurred in 1.4% of cases, hemorrhage in
      1.2%, and wound infection in 0.3%. No deaths were reported. A significant rate of
      LRN damage was noted, which has an important impact on the patient's social life.
      Hypoparathyroidism after total thyroidectomy is an important complication that
      can be successfully treated by therapy, although it is not always easily managed
      in special circumstances such as in young persons or pregnant women. The
      complications associated with thyroid surgery must be kept in mind so the surgeon
      can carefully evaluate the surgical and medical therapeutic options, have more
      precise surgical indications, and be able to give the patient adequate
      information.

PMID- 14961205
TI  - Evaluation of heritage trees for conservation and management in Guangzhou City
      (China).
AB  - The recent fast pace of urbanization in China and other developing countries has
      exerted pressure on urban trees, which constitute a key urban environmental
      asset. The most outstanding trees should be treated as natural-cum-cultural
      heritage. Guangzhou City's growth has threatened its rich urban-tree endowment, a
      diversified assemblage of 200,000 trees represented by 254 species and located in
      three major habitats: roadside, park, and institutional grounds. Mainly based on
      age and performance, 348 trees were officially designated as heritage specimens.
      They were evaluated in the field for tree dimensions, habitat, performance, and
      landscape contribution, to establish enhanced conservation and management
      strategies. With only 25 species, heritage trees were dominated by five
      cultivated natives and encompass some of the city's rare species; some common
      urban-forest species were not represented. Older districts and roadside habitats,
      despite their compact town plan and limited growing space, had the largest tree
      dimensions and largest share of heritage trees. Many heritage trees were large
      with long life expectancy and the potential for biomass expansion, and had
      pivotal cityscape impacts where they occur. Old neighborhoods, traditional haven
      for the arborescent treasure, are being changed by construction activities and
      periodic typhoon and windstorm damages. Increasing development density could
      degrade the heritage trees and their growing space, and reduce tree quality and
      life span. Upgrading the statutory-administrative systems and arboricultural care
      can enhance long-term survival of the precious natural-cum-cultural heritage. The
      experience of Guangzhou in identifying and preserving its high-quality urban
      trees can provide management strategies for other cities.

PMID- 14961206
TI  - Ecotourism and community development: case studies from Hainan, China.
AB  - The connections between people, parks, and tourism have received significant
      attention in recent years, recognizing the potential for mutually beneficial
      relationships. Ecotourism has been promoted and widely adopted as a strategy for
      funding conservation initiatives, while at the same time contributing to the
      socioeconomic development of host communities and providing for quality tourism
      experiences. Parks are among the most common ecotourism destinations. Employing
      interviews, observations and secondary sources, this study assesses the current
      status of ecotourism at two protected areas in Hainan, China, where it is being
      promoted as a strategy for balancing regional economic growth and conservation
      objectives. Through an evaluation of the existing tourism-park-community
      relationships, opportunities and constraints are identified. Ecotourism
      development was found to be at an early stage at both study sites. Socioeconomic
      benefits for the local communities have been limited and tourism activity has not
      contributed revenues towards conservation to date. Community residents,
      nevertheless, generally support conservation and are optimistic that tourism
      growth will yield benefits. In light of the study findings and the salient
      literature, planning direction is offered with the intention of enhancing the
      capacity of ecotourism to generate benefits for both communities and the parks,
      and thus contribute to the sustainable development of the region more generally.
      Lessons derived have broad applicability for ecotourism destinations elsewhere.

PMID- 14961208
TI  - Comparison of microcomputed tomographic and microradiographic measurements of
      cortical bone porosity.
AB  - Cortical bone is perforated by a network of canals that have a significant impact
      upon its material properties. Microcomputed tomography offers the possibility of
      noninvasively visualizing and quantifying cortical pores in both two and three
      dimensions. Establishing how two-dimensional (2D) microcomputed tomographic
      (microCT) analysis compares with conventional methods for analyzing cortical
      porosity is an important prerequisite for the wider adoption of this technique
      and the development of three-dimensional (3D) analysis. Therefore, we compared
      porosity-related parameters from 2D microcomputed tomographic images with those
      from matching microradiographic sections. Samples from five human femora were
      scanned at a 10-microm resolution and then sequentially sectioned and
      microradiographed. An average of eight image pairs were produced from each femur
      (total, n = 41). The repeatability and comparability of the two techniques was
      assessed for three parameters; cortical porosity (%), mean pore area (microm(2)),
      and pore density (pores/mm(2)). For repeatability, no significant difference ( P
      > 0.05) was found between the two methods for cortical porosity and mean pore
      area; however, pore density differed significantly ( P < 0.001). For
      comparability, the bias (+/- error) between the methods was found to be 0.51% (+/
      0.31%) for cortical porosity and -155 microm(2) (+/-293 microm(2)) for mean pore
      area. The bias for pore density was dependent upon measurement size with
      microcomputed tomographic images having 14% (+/-9.3%) fewer pores per millimeter
      squared. The qualitative and quantitative similarities between the two techniques
      demonstrated the utility of 2D microcomputed tomographic for cortical porosity
      analysis. However, the relatively poor results for pore density revealed that a
      higher resolution (<10 microm) is needed to consistently visualize all cortical
      pores in human bone.

PMID- 14961209
TI  - Growth of C57BL/6 mice and the material and mechanical properties of cortical
      bone from the tibia.
AB  - Murine models are becoming increasingly important for studying skeletal growth
      and regulation because of the relative ease with which their genomes can be
      manipulated. This study measured the changes in cortical bone of tibiae from one
      of the more common models, the C57Bl/6, as a function of aging. A total of 97
      mice, male and female, were studied at the ages of 1, 2, 3, 6, 9, and 12 months.
      The body weight of the animals, the length of the tibiae, the composition (in
      terms of mineral and organic mass fractions), and the density and modulus of the
      bone were measured. Peripheral quantitative computed tomography was also used to
      measure bone mineral density (BMD), total and cortical areas, and the cross
      sectional moment of inertia. Most parameters measured followed a growth-like
      curve, which leveled off some time before 6 months of age. Bone composition and
      modulus were the same at maturity in both sexes, but there were sex-related
      differences in the modulus with aging. Dimensional measurements and the density
      of the bone showed significant differences between male and female animals at all
      ages, with the male mice having larger values. Skeletal maturity for most factors
      in C57Bl/6 mice has been reached before the age of 6 months.

PMID- 14961210
TI  - Mechanical stimulation promotes osteogenic differentiation of human bone marrow
      stromal cells on 3-D partially demineralized bone scaffolds in vitro.
AB  - Bone is a dynamic tissue that is able to sense and adapt to mechanical stimuli by
      modulating its mass, geometry, and structure. Bone marrow stromal cells (BMSCs)
      are known to play an integral part in bone formation by providing an
      osteoprogenitor cell source capable of differentiating into mature osteoblasts in
      response to mechanical stresses. Characteristics of the in vivo bone environment
      including the three dimensional (3-D) lacunocanalicular structure and
      extracellular matrix composition have previously been shown to play major roles
      in influencing mechanotransduction processes within bone cells. To more
      accurately model this phenomenon in vitro, we cultured human BMSCs on 3-D,
      partially demineralized bone scaffolds in the presence of four-point bending
      loads within a novel bioreactor. The effect of mechanical loading and
      dexamethasone concentration on BMSC osteogenic differentiation and mineralized
      matrix production was studied for 8 and 16 days of culture. Mechanical
      stimulation after 16 days with 10 nM dexamethasone promoted osteogenic
      differentiation of BMSCs by significantly elevating alkaline phosphatase activity
      as well as alkaline phosphatase and osteopontin transcript levels over static
      controls. Mineralized matrix production also increased under these culture
      conditions. Dexamethasone concentration had a dramatic effect on the ability of
      mechanical stimulation to modulate these phenotypic and genotypic responses.
      These results provide increased insight into the role of mechanical stimulation
      on osteogenic differentiation of human BMSCs in vitro and may lead to improved
      strategies in bone tissue engineering.

PMID- 14961213
TI  - Weak evidence of thyrotropin receptors in primary cultures of human osteoblast
      like cells.
AB  - Extra-thyroidal thyrotropin (TSH) receptors (TSHRs) have been demonstrated in
      several tissues and cells, including human and rat osteosarcoma cell lines. We
      have explored whether human TSHR (hTSHRs) also are present in primary cultures of
      human osteoblast-like (hOB) cells. [(125) I]TSH binding was limited in hOB cells,
      but somewhat higher in UMR 106-01 cells and considerably higher in hTSHR
      transfected CHO cells. In hOB cells, the basal intracellular cAMP levels
      increased 282% after stimulation with 10 U/L TSH. In the hTSHR-transfected CHO
      cells, the cAMP increase was 3030% in response to 10 U/L TSH and 1240% after 1
      U/L TSH. Free cytoplasmic calcium did not change in response to TSH in hOB cells.
      HTSHR mRNA was detected in hOB cells from 3/4 bone by reverse transcriptase
      polymerase chain reaction RT-PCR and nucleotide sequencing HTSHR mRNA, but could
      not be demonstrated with the RNase protection technique in hOB cells from 5
      different donors. In conclusion, even after the use of several methods, we have
      found only weak evidence for expression and presence of functionally active hTSHR
      in hOB cells. Given the low level of expression, specific binding and cAMP
      signaling, we suggest that it is unlikely that circulating TSH plays a
      physiological role for bone metabolism mediated through osteoblasts.

PMID- 14961214
TI  - Quantitative radiographic assessment of cancellous bone changes in the proximal
      tibia after total knee arthroplasty: a 3-year follow-up study.
AB  - The objective of this study was to determine whether fractal signature analysis
      (FSA) of digitized macroradiographs of knees with prosthetic implants quantifies
      alterations in tibial trabecular structure surrounding the implant over a 3-year
      period. Nineteen knees (16 patients) with arthroplasty had macroradiographs (x4)
      at baseline and annually for 3 years. The regions of interest (ROIs) were located
      in the medial and lateral plateau, midstem, and apical sites. FSA of horizontal
      and vertical trabecular organization was measured at each ROI, and the changes at
      the yearly visits were compared to the baseline values. Compared to the baseline
      values, FSA of the first-year radiographs detected a significant ( P < 0.05)
      decrease in the number of vertical trabeculae in the medial compartment, and
      vertical, and horizontal trabeculae in the lateral compartment. During the second
      year, bone remodeling led to an increase in the number of horizontal trabeculae
      in the medial compartment, and vertical, and horizontal trabeculae in the lateral
      compartment. During the third year, there was a significant increase ( P < 0.05)
      in the number of vertical and some horizontal trabeculae in both the medial and
      lateral compartments. Overall trabecular changes were significantly greater in
      the lateral than in the medial compartment. Following total knee arthroplasty,
      the response of bone showed that the first year was characterized by trabecular
      loss in response to posttraumatic osteopenia following surgery. By the third
      year, this process had reversed, with a significant increase in mainly vertical
      and some horizontal trabeculae in both the medial and lateral compartments, with
      only the lateral compartment showing an overall loss in small- and medium-sized
      trabeculae by the end of the study period.

PMID- 14961215
TI  - Evaluation of ability of biochemical markers of bone turnover to predict a
      response to increased doses of HRT.
AB  - Antiresorptive therapy is usually given in a fixed dose, and we hypothesized that
      some patients receiving standard doses of hormone replacement therapy (HRT) might
      benefit from a higher dose, particularly if their bone turnover decreases after
      increasing the dose of HRT. Eighty-eight women who had been receiving standard
      dose (0.625 mg/day) conjugated equine estrogens (CEE) for at least one year were
      randomized to take either standard-dose (0.625 mg/day, n = 36) or high-dose (1.25
      mg/day, n = 52) therapy. Subjects with a uterus were allowed to take either 10 mg
      of medroxyprogesterone cyclically or 5 mg daily, according to personal
      preference. Bone Mineral Density (BMD) and biochemical markers of bone turnover
      were followed for 2 years. Mean bone turnover decreased significantly (-4.1% to 
      19.1%) after 6 months of high-dose CEE. Decreases in serum BSAP (bone-specific
      alkaline phosphatase) and serum or urine NTX ( N-terminal telopeptide crosslink
      of type I collagen) on high-dose therapy were not predictive of an improvement in
      BMD, but a decrease in serum CrossLaps did predict an improvement in BMD. Mean
      change in BMD in subjects with a significant decrease in serum CrossLaps at the
      anteroposterior spine was 3.1% +/- 3.9% versus 1.2% +/- 2.9% for subjects with no
      significant change in CrossLaps, P < 0.02. There was, however, a wide range of
      changes in BMD in patients with or without a significant change in CTX on high
      dose HRT, making it impossible to predict an improvement in BMD based on an
      individual's changes in turnover. Measuring of bone density and bone turnover
      with better precision might be more successful in guiding individual dosing of
      antiresorptive therapy.

PMID- 14961216
TI  - Quantitative ultrasound measurements in children and adolescents with: type 1
      diabetes.
AB  - The aim of the current study was to evaluate bone status at the radius and
      phalanx in children and adolescents with type 1 diabetes by using quantitative
      ultrasound (QUS) measurements. Thirty pediatric patients, 16 male and 14 female,
      with type 1 diabetes of duration of 5 to 177 months and mean (+/- SD) age 11.3 +/
      4.6 years were studied. QUS measurements were carried out using the Sunlight
      Omnisense 7000 S device. Speed of sound (SOS) was measured at the radius and
      tibia. Diabetic control was assessed by glycosylated hemoglobin (HbA(1c))
      measurements. Male and female patients with type 1 diabetes did not have
      significantly different SOS or HbA(1c) values. SOS Z-scores at both the radius
      and tibia were negatively associated with duration of disease ( r = -0 41 and r =
      -0.37 for the radius and tibia respectively, P < 0.05 for both correlations).
      Seven of 15 patients with duration of disease of >6 years had diminished SOS,
      defined as Z-score of <-1, at either the radius or tibia. SOS measurements at the
      radius showed moderate correlation with SOS at the tibia ( r = 0.58, P < 0.00 l).
      There was no correlation between SOS and HbA(1c). In conclusion, SOS Z-scores at
      both the radius and tibia show a significant negative correlation with duration
      of insulin-dependent diabetes in children. No relation was found between SOS and
      metabolic control of young diabetic patients.

PMID- 14961225
TI  - PACS training modules at Texas Children's Hospital.
AB  - In 1999, the Performance Improvement Committee of the Diagnostic Imaging Services
      of Texas Children's Hospital identified the need for smoother integration of the
      picture archiving and communications system (PACS) technology into the workflow
      of the rest of the department. An effort was then launched to document prevalent
      issues, as well as to define the processes needed to implement a department-wide
      program to acquaint the staff with this new technology. The department's
      application trainer, with the guidance of the Performance Improvement Committee,
      spearheaded the design and implementation of the PACS training program and has
      continued to develop it during the past 2 years. This article describes the
      format and components of the PACS training modules now in use, and details some
      of the positive effects of this effort.

PMID- 14961226
TI  - Sharks: a potential source of antiangiogenic factors and tumor treatments.
AB  - Since angiogenesis is a key feature of tumor growth, inhibiting this process is
      one way to treat cancer. Cartilage is a natural source of material with strong
      antiangiogenic activity. This report reviews knowledge of the anticancer
      properties of shark cartilage and clinical information on drugs such as neovastat
      and squalamine. Because their entire endoskeleton is composed of cartilage,
      sharks are thought to be an ideal source of angiogenic and tumor growth
      inhibitors. Shark cartilage extract has shown antiangiogenic and antitumor
      activities in animals and humans. The oral administration of cartilage extract
      was efficacious in reducing angiogenesis. Purified antiangiogenic factors from
      shark cartilage, such as U-995 and neovastat (AE-941), also showed antiangiogenic
      and antitumor activity. AE-941 is under phase III clinical investigation.
      Squalamine, a low molecular weight aminosterol, showed strong antitumor activity
      when combined with chemotherapeutic materials. The angiogenic tissue inhibitor of
      metalloprotease 3 (TIMP-3) and tumor suppressor protein (snm23) genes from shark
      cartilage were cloned and characterized.

PMID- 14961227
TI  - Expression profile of the channel catfish spleen: analysis of genes involved in
      immune functions.
AB  - Both qualitative and quantitative patterns of tissue-specific gene expression can
      be determined using gene profiling. Expressed sequence tag (EST) analysis is an
      efficient approach not only for gene discovery and examining gene expression, but
      also for development of molecular resources useful for functional genomics. As
      part of an ongoing transcriptome analysis of channel catfish (Ictalurus
      punctatus), EST analysis was conducted for gene annotations and profiling using a
      complementary DNA library developed from messenger RNA of the spleen. A total of
      1204 spleen cDNA clones were analyzed. Of the 1204 clones, 665 clones (55.2%)
      were identified as orthologs of known genes from other organisms by BLAST
      searches and 539 clones (44.8%) as unknown gene clones. In total 147 novel genes
      were identified, and annotations were made to 118 of them. In addition, 389 novel
      EST clusters were identified. Expression profile was analyzed in relation to
      metabolic functional groups. A total of 28 known genes were involved in immune
      functions, of which 10 were identified for the first time in channel catfish.
      Microsatellite-containing clones were also identified that may be potentially
      useful for genome mapping. This work contributed to the Catfish Gene Index, and
      toward a Unigene set useful for functional genomics research concerning spleen
      gene functions in relation to disease defenses.

PMID- 14961228
TI  - Characterization of muscle-regulatory genes, Myf5 and myogenin, from striped bass
      and promoter analysis of muscle-specific expression.
AB  - Myf5 and Myogenin are basic helix-loop-helix transcription factors that belong to
      the muscle regulatory factor (MRF) gene family, which plays important roles in
      regulating skeletal muscle development and growth. Members of the MRF family,
      including Myf5, MyoD, Myogenin, and MRF4 are specifically expressed in skeletal
      muscle cells. They have the remarkable property of converting a variety of cells
      into myoblasts and myotubes when ectopically expressed in other cell types. To
      better understand their role and regulation of expression in fish muscle cells,
      Myf5 and myogenin genomic genes were isolated from striped bass (Morone
      saxatilis). Sequence analysis revealed that these 2 genes shared similar
      structures. They both contained 3 exons and 2 introns, and a highly conserved
      basic helix-loop-helix domain. Promoter analysis identified several putative E
      box sites in both Myf5 and myogenin promoters that might confer muscle-specific
      expression. To determine if the striped bass Myf5 and myogenin promoters could
      control muscle-specific expression, the Myf5 or myogenin promoter was linked with
      the green fluorescent protein (GFP) reporter gene, and their promoter activity
      was analyzed in zebrafish embryos by transient expression assay. Our data showed
      that both striped bass Myf5 and myogenin promoters could drive muscle-specific
      GFP expression in zebrafish. These data demonstrated that a muscle-specific
      regulatory element or elements were located within the striped bass Myf5 and
      myogenin promoters, and were conserved between striped bass and zebrafish.
      Moreover, these data suggested the muscle-specific regulatory element could
      function across fish species in regulating gene expression.

PMID- 14961229
TI  - Synthesis of the neurotoxin quinolinic acid in apoptotic tissue from Suberites
      domuncula: cell biological, molecular biological, and chemical analyses.
AB  - Sessile marine animals, such as sponges, are prone to infection by prokaryotic as
      well as by eukaryotic attacking organisms. Using the sponge Suberites domuncula
      we document for the first time that in its apoptotic tissue a toxic compound is
      produced that very likely controls the elimination of the dying tissue. Apoptosis
      was induced by exposing the sponges to 2,2'-dipyridyl or by maintaining them
      under nonaeration conditions. After that treatment at least one eukaryotic
      epibiont (Bittium sp.) could be found grazing on apoptotic tissue. Cell
      proliferation assays demonstrated that aqueous extracts from unaffected sponge
      tissue displayed no cytotoxicity. However, addition of an extract from apoptotic
      tissue to neuronal cells from rat brain exerted strong toxicity. The underlying
      compound was identified as quinolinic acid; quantitative determination showed
      that quinolinic acid is present only in apoptotic tissue (4.8 mg/g dry wet
      weight). The complementary DNA encoding the key enzyme of the quinolinic acid
      pathway, 3-hydroxyanthranilate 3,4-dioxygenase, was cloned and characterized. The
      expression of this gene is up-regulated in apoptotic tissue. These data suggest
      that a complex molecular network controls apoptotic elimination of sponge tissue,
      which results in the synthesis of the bioactive compound quinolinic acid that
      controls the elimination of the tissue, perhaps via differential effects on
      grazing epibionts.

PMID- 14961230
TI  - Bioremediation of fish cannery wastewater with yeasts isolated from a drainage
      canal.
AB  - Several yeasts were isolated from a drainage canal in a Japanese fish food
      processing factory. They were characterized by the decomposition of organic
      polymers such as proteins and reducing sugars, their growth in the wastewater,
      the decrease in total organic carbon (TOC), and taxonomy. Three strains of yeast
      dominated the sample: Debaryomyces occidentalis (P1), Trichosporon ovoides (P19),
      and a strain that could not be identified (S27). Strain P19 had the highest TOC
      decreasing activity and was immobilized onto chitosan beads. The immobilized
      yeasts reduced the TOC from 1.2 x 10(3) to 3.0 x 10(2) mg of C/L per day in the
      fish cannery wastewater.

PMID- 14961231
TI  - kappa-Carrageenan gel as agent to sequester paralytic shellfish poison.
AB  - The action of k-carrageenan gel to sequester paralytic shellfish poison (PSP) was
      tested and characterized. When an extract from a Philippine strain of Pyrodinium
      bahamense var. compressum was used as PSP solution, the PSP-sequestering property
      of kappa-carrageenan gel was found to be dependent on gel surface area,
      interaction time, and polysaccharide concentration. The interaction was also
      found to be affected by high concentrations of monovalent cations. The
      characteristics of kappa-carrageenan as a PSP-sequestering agent all point to
      cation exchange as its mechanism of action. It is also proposed that the
      polysaccharide gel can be utilized as an agent to alleviate PSP intoxication.

PMID- 14961232
TI  - Accumulation of H+ in vacuoles induced by a marine peptide toxin, theonellamide
      F, in rat embryonic 3Y1 fibroblasts.
AB  - The effects of theonellamide F, a marine bicyclic peptide, on vacuolar formation
      in cultured cells were studied. Theonellamide F induced large vacuoles in 6 types
      of mammalian cells. The vacuoles induced by theonellamide F in 3Y1 cells
      accumulated acridine orange, a fluorescent probe indicating the presence of an
      acidic organelle. Their disappearance following treatment with bafilomycin A1
      suggests that these vacuoles contain vacuolar ATPase to maintain an acidic
      internal milieu, and this is similar to those induced by Helicobacter pylori
      toxin VacA. The vacuoles induced by theonellamide F were not significantly
      decreased in size or number by nocodazole treatment, and the localization of a
      small GTPase, rab7, did not always correspond to the outline of the vacuoles.
      These results suggest that the molecular mode of action of vacuolar formation by
      theonellamides may differ from that by VacA and can be considered unique.

PMID- 14961233
TI  - Analyses of nuclear ldhA gene and mtDNA control region sequences of Atlantic
      northern bluefin tuna populations.
AB  - There has been considerable debate about whether the Atlantic northern bluefin
      tuna exist as a single panmictic unit. We have addressed this issue by examining
      both mitochondrial DNA control region nucleotide sequences and nuclear gene ldhA
      allele frequencies in replicate size or year class samples of northern bluefin
      tuna from the Mediterranean Sea and the northwestern Atlantic Ocean. Pairwise
      comparisons of multiple year class samples from the 2 regions provided no
      evidence for population subdivision. Similarly, analyses of molecular variance of
      both mitochondrial and ldhA data revealed no significant differences among or
      between samples from the 2 regions. These results demonstrate the importance of
      analyzing multiple year classes and large sample sizes to obtain accurate
      estimates when using allele frequencies to characterize a population. It is
      important to note that the absence of genetic evidence for population
      substructure does not unilaterally constitute evidence of a single panmictic
      population, as genetic differentiation can be prevented by large population sizes
      and by migration.

PMID- 14961234
TI  - Spatial homogeneity and temporal heterogeneity of red drum (Sciaenops ocellatus)
      microsatellites: effective population sizes and management implications.
AB  - The red drum (Sciaenops ocellatus) is one of a number of species that occupy
      estuarine waters as juveniles and migrate to open ocean waters as adults. This
      species has experienced dramatic declines in population numbers over the past 2
      decades, which has prompted increasing fishery restriction. In addition, hatchery
      augmentation has been initiated by several states to increase the abundance of
      juveniles in local areas. In South Carolina hatchery-reared fish have made
      significant (20%) contributions to the juvenile population on very local scales.
      As hatchery-reared fish are typically produced by a small number of individuals,
      the genetic consequences of augmentation programs are of concern. In this article
      we assess genetic variation at 5 microsatellite loci in S. ocellatus. The data
      indicate little geographic differentiation among samples collected along the
      Atlantic Coast of the United States, but substantial differences among year
      classes taken from South Carolina. The gene frequency differences among year
      classes were used to estimate the effective population size (Nc) of S. ocellatus
      in South Carolina and suggested that Ne was less than 300 from 1990 to 1993 and
      increased to about 1000 in 1994 and 1995. Whether this increase reflects the
      effectiveness of management regulations or simply a random fluctuation in S.
      ocellatus populations is not clear. The data suggest that a limited number of
      individuals produce the bulk of a given year class and support the sweepstakes
      hypothesis. Given the small Ne and estimates of the contribution of hatchery
      reared fish to the wild stock, it is suggested that programs have the potential
      to increase, rather than decrease; Ne in the wild.

PMID- 14961235
TI  - Effect of rainbow trout growth hormone complementary DNA on body shape, carcass
      yield, and carcass composition of F1 and F2 transgenic common carp (Cyprinus
      carpio).
AB  - The effect of rainbow trout growth hormone complementary DNA on body shape, dress
      out yield, and body composition were assessed in the F1 and F2 generations of
      transgenic common carp (Cyprinus carpio). All measurements were compared with
      those for nontransgenic full-sibling common carp in their respective families,
      and the fish were communally evaluated in earthen ponds. The body weight and
      length were highly correlated (P <0.01) in both genotypes in all the families.
      Head morphometrics were negatively correlated (P <0.05) to weight and length of
      the fish. Various head, body, and caudal traits grew disproportionately faster in
      transgenic fish in both generations. The altered body shape of transgenic fish
      resulted in improved dressing percentage in the F2 generation. The carcass
      composition of transgenic muscle had a lower percentage of (P <0.01) moisture and
      lipids and higher (P <0.01) percentage of protein in both generations. Six of the
      18 amino acids analyzed in F1 transgenic common carp muscle were higher F1 (P
      <0.05) than the control genotype; however, amino acid ratios were minimally
      changed. Also, the fatty acid profiles of both genotypes were minimally altered.
      Higher histidine and lysine ratios in the diet are recommended for maximum growth
      and health of transgenic common carp in intensive culture systems on the basis of
      essential amino acid ratios.

PMID- 14961236
TI  - Isolation of Haliclonamides: new peptides as antifouling substances from a marine
      sponge species, Haliclona.
AB  - Bioassay-guided fractionation of an extract of a marine sponge species,
      Haliclona, led to the isolation and identification of new peptides,
      Haliclonamides C, D, and E. Their structures were determined by spectroscopic
      methods. These compounds showed repellent activity against the blue mussel
      Mytilus edulis galloprovincialis.

PMID- 14961237
TI  - Purification of anti-HIV protein from purple fluid of the sea hare Bursatella
      leachii de Blainville.
AB  - The purple fluid of Bursatella leachii, already found to have anti-HIV activity,
      was selected and tested for purification and characterization of an anti-HIV
      protein. Only one fraction showed anti-HIV activity at the minimum inhibition
      concentration of 50 mg/ml. This purified anti-HIV protein has been named as
      "Bursatellanin-P" after the animal species Bursatella leachii. About 3 mg of the
      pure protein was obtained from 1000 ml of purple fluid. The anti-HIV activity
      increased by about 135-fold in the purified sample, as compared with the crude
      purple fluid. The purified protein, which showed anti-HIV activity, was a single
      unit with a molecular weight of 60 kDa. The protein was stable between pH 5.8 and
      8.0. It lost its activity with heating at 60 degrees C for 10 minutes and also
      with extreme pH values of 2.0 or 10. The protein was resistant to digestion of
      proteinase K and mercaptoethanol.

PMID- 14961238
TI  - Development of a monoclonal antibody detection assay for species-specific
      identification of abalone.
AB  - Species identification based on biochemical and molecular techniques has a broad
      range of applications. These include compliance enforcement, the management and
      conservation of marine organisms, and commercial quality control. Abalone
      poaching worldwide and illegal trade in abalone products have increased mainly
      because of the attractive prices obtained and caused a sharp decline in stocks.
      Alleged poachers have been acquitted because of lack of evidence to correctly
      identify species. Therefore, a robust method is required that would identify
      tissue of abalone origin to species level. The aim of this study was to develop
      immunologic techniques, using monoclonal and polyclonal antibodies, to identify
      10 different abalone species and subspecies from South Africa, the United States,
      Australia, and Japan. The combination of 3 developed monoclonal antibodies to
      South African abalone (Haliotis midae) enabled differentiation between most of
      the 10 species including the subspecies H. diversicolor supertexta and H.
      diversicolor diversicolor. In a novel approach, using antibodies of patients with
      allergy to abalone, the differentiation of additional subspecies, H. discus
      discus and H. discus hannai, was possible. A field-based immunoassay was
      developed to identify confiscated tissue of abalone origin.

PMID- 14961239
TI  - Molecular cloning of cDNAs encoding two pigment-dispersing hormones and two
      corresponding genes from the kuruma prawn (Penaeus japonicus).
AB  - Pigment-dispersing hormone (PDH) controls pigment dispersion in chromatophores.
      In this study cDNAs encoding 2 PDH precursors of the kuruma prawn (Penaeus
      japonicus) (Pej-PDH-I and Pej-PDH-II) were cloned. Both precursors consisted of a
      signal peptide, a PDH-precursor-related peptide (PPRP), and PDH. The PPRPs were
      homologous to those in other crustacean species, but not to those of pigment
      dispersing factors (PDFs) in insects, which were members of the PDH/PDF family.
      Two corresponding genes were also cloned. Sequence analyses revealed that the Pej
      PDH-I gene had 3 exons separated by 2 introns, while the Pej-PDH-II gene had 2
      exons separated by 1 intron. The exon/intron organizations in the PDH genes were
      different from that of the Drosophila melanogaster PDF gene, which is intronless.
      Analyses by reverse transcription polymerase chain reaction demonstrated that
      both transcripts existed only in the eyestalk, but not in the brain, thoracic
      ganglia, abdominal ganglia, hindgut, or hepatopancreas.

PMID- 14961240
TI  - Genetic analysis of the populations of Japanese anchovy (Engraulidae: Engraulis
      japonicus) using microsatellite DNA.
AB  - We analyzed the population structure of the Japanese anchovy (Engraulis
      japonicus), a small pelagic fish, using 6 microsatellite DNA loci. The anchovy is
      known to have 2 separate spawning populations, one near northeastern Taiwan in
      the Pacific Ocean and the other near southwestern Taiwan in the Taiwan Strait.
      The planktonic larvae then drifted north to the feeding grounds in the East China
      Sea to advance in their life history. Three populations of the anchovy were
      analyzed, including 2 temporal population from the northeastern spawning ground
      (I-Lan 1999 and I-Lan 2000) and one population from the southwestern spawning
      ground (Peng-Hu 2000). The genetic variability of the 6 loci was high for all the
      populations. The average numbers of alleles per population ranged from 25.5 to
      32.3, and the average observed heterozygosity ranged from 0.559 to 0.650. A
      significant population differentiation was found between geographic populations
      but not between the temporal populations. However, the level of geographic
      differentiation was weak, average FST 0.0088. The significant geographic
      population structure indicated that the populations of 2 spawning grounds
      belonged to separate stocks. Moreover, 16 of the 18 population-locus cases showed
      significant departure from Hardy-Weinberg equilibrium, implying that each
      spawning population in turn consisted of mixed native stocks. Finally, we posed 3
      population models to be evaluated against the genetic data disclosed with the
      microsatellite markers.

PMID- 14961241
TI  - Gal4-gene-dependent alterations of embryo development and cell growth in primary
      culture of sea urchins.
AB  - Primary cell cultures from sea urchins have a low proliferative level that
      prevents the establishment of long-term cultures. To increase expression levels
      of the genes regulating cell growth in sea urchins, and thus enhance cell growth,
      we used the transcriptional activator gene Gal4 found earlier in yeast. Sea
      urchin embryos were treated with plasmid DNA containing the Gal4 gene. Expression
      of the transgene was confirmed by reverse transcriptase polymerase chain
      reaction. When the fully functional gene was used, embryos effectively formed
      teratoma-like structures after 50 to 55 hours of cultivation. In contrast, the
      Gal4 gene, devoid of acidic activating regions, possessed little activity as a
      teratogen. The Gal4-treated cells in blastula-derived culture showed higher DNA
      synthesis and higher proliferative activity than control cells. We suggest that
      formation of the teratoma-like structures in embryos, activation of DNA
      synthesis, and significant increase of cell number in embryo-derived cell
      cultures could be attributed to Gal4 gene action.

PMID- 14961242
TI  - Identification of immune-related genes in hemocytes of black tiger shrimp
      (Penaeus monodon).
AB  - An expressed sequence tag (EST) library was constructed from hemocytes of the
      black tiger shrimp (Penaeus monodon) to identify genes associated with immunity
      in this economically important species. The number of complementary DNA clones in
      the constructed library was approximately 4 x 10(5). Of these, 615 clones having
      inserts larger than 500 bp were unidirectionally sequenced and analyzed by
      homology searches against data in GenBank. Significant homology to known genes
      was found in 314 (51%) of the 615 clones, but the remaining 301 sequences (49%)
      did not match any sequence in GenBank. Approximately 35% of the matched ESTs were
      significantly identified by the BLASTN and BLASTX programs, while 65% were
      recognized only by the BLASTX program. Of the 615 clones, 55 (8.9%) were
      identified as putative immune-related genes. The isolated genes were composed of
      those coding for enzymes and proteins in the clotting system and the
      prophenoloxidase-activating system, antioxidative enzymes, antimicrobial
      peptides, and serine proteinase inhibitors. Three full-length ESTs encoding
      antimicrobial peptides (antilipopolysaccharide and penaeidin homologues) and a
      heat shock protein (cpn10 homologue) are reported.

PMID- 14961243
TI  - Identification of four scallop species using PCR and restriction analysis of the
      ribosomal DNA internal transcribed spacer region.
AB  - Polymerase chain reaction (PCR) and restriction fragment length polymorphism
      (RFLP) analysis of the ribosomal DNA region spanning the 5.8S RNA gene and the 2
      flanking internal transcribed spacers (ITSs) was performed to establish DNA-based
      molecular markers for the identification of the scallops Aequipecten opercularis,
      Chlamys distorta, Mimachlamys varia, and Pecten maximus. Chlamys distorta was
      distinguished simply by ITS size. Species-specific restriction patterns were
      found with the restriction enzyme AluI, and also with SmaI for A. opercularis and
      M. varia. When ITS sizes and the RFLPs obtained with SmaI were combined, the 4
      scallops were also differentiated. Additional species-specific RFLPs were
      revealed after ITS-2 PCR amplification and subsequent digestion with Hsp92II.
      Using this marker, canned scallops were identified. Thus this work provides a
      simple, reliable, and rapid method for the identification of scallops that can be
      used when species-specific morphologic characteristics are removed or when
      specimens are small in size.

PMID- 14961244
TI  - Novel microsatellites from asian sea bass (Lates calcarifer) and their
      application to broodstock analysis.
AB  - We isolated novel dinucleotide, trinucleotide, and tetranucleotide
      microsatellites from the genome of Asian sea bass (Lates calcarifer). Two genomic
      DNA libraries were established, one was enriched for (CA)n repeats, while the
      other for (GATA)n, (GACA)n, and (AAC)n repeats. Sixty clones containing an insert
      between 250 and 1000 bp in size were sequenced from each library; altogether 50
      (43%) of them contained microsatellites. Forty microsatellites were characterized
      in 16 unrelated Asian sea bass individuals. Twenty-eight of them (70%) showed
      specific amplification and polymorphism. The allele number per loci varied
      between 2 and 20 with an average of 5.3, while expected heterozygosity ranged
      from 0.31 to 0.95 with an average of 0.64. At some loci allele sizes spread over
      a wide range (>100 bp). No significant correlation (r = 0.23, df = 31, P > 0.05)
      was found between the repeat number and the number of alleles. A whole broodstock
      containing 170 individuals was analyzed by using 8 selected polymorphic
      microsatellites. The average number of alleles per locus was 11.8 (range, 4-21).
      The expected heterozygosity ranged from 0.57 to 0.90 with an average of 0.75,
      while the fixation index was 0.02. Genetic similarity between individuals ranged
      from 0 to 0.72. Comparison of allele frequencies between the broodstock and the
      24 nonrelated individuals revealed some unique alleles.

PMID- 14961245
TI  - Molecular cloning and characterization of two Na/K-ATPase isoforms in Fundulus
      heteroclitus.
AB  - Na/K-ATPase plays an important role in ion regulation in teleost fishes. In most
      taxa several isoforms exist to provide physiological versatility to specific cell
      types, but little is known about Na/K-ATPase isoforms in fish. A reverse
      transcriptase polymerase chain reaction approach was used to identify Na/K-ATPase
      a-subunit isoforms from the gill and muscle of an estuarine teleost, Fundulus
      heteroclitus. Full-length complementary DNA sequences were similar at both the
      nucleotide level (74.4%) and the amino acid level (82.5%). Phylogenetic analysis
      indicated that the gill isoform was similar to the mammalian a1 subunit and the
      muscle isoform was similar to the mammalian a2 subunit. Northern blotting and
      isoform-specific polymerase chain reaction were used to determine the tissue
      distribution of the isoforms. The gill (a1) isoform was expressed in all tissues,
      while the muscle (a2) isoform had a much more restricted expression pattern,
      being present at high levels only in muscle and brain, consistent with the
      distributions of these isoforms in mammals.

PMID- 14961246
TI  - Oligonucleotide primers for PCR amplification of coelomate introns.
AB  - Abstract Seven novel oligonucleotide primer pairs for polymerase chain reaction
      amplification of introns from nuclear genes in coelomates were designed and
      tested. Each pair bound to adjacent exons that are separated by a single intron
      in most coelomate species. The primer sets amplified introns in species as widely
      separated by the course of evolution as oysters (Mollusca: Protostoma) and salmon
      (Chordata: Deuterostoma). Each primer set was tested on a further 6 coelomate
      species and found to amplify introns in most cases. These primer sets may
      therefore be useful tools for developing nuclear DNA markers in diverse coelomate
      species for studies of population genetics, phylogenetics, or genome mapping.

PMID- 14961247
TI  - Surface attachment induced production of antimicrobial compounds by marine
      epiphytic bacteria using modified roller bottle cultivation.
AB  - A modified roller bottle culture method elicited the production of antimicrobial
      compounds from 2 epibiotic marine bacterial strains, EI-34-6 and II-111-5,
      isolated from the surface of the marine alga Palmaria palmata. These isolates,
      tentatively identified as Bacillus species, were grown as a biofilm on the
      surface of nutrient glycerol ferric agar (NGFA) and marine Columbia glycerol agar
      (MCGA) on the inside of a rolling bottle. The biofilm was shown to be stable, and
      the cells were difficult to remove from the agar surface. The culture supernatant
      exhibited a different antibiotic spectrum when the strains were grown using the
      agar roller bottle method compared with shake flask cultures or nonagar roller
      bottle cultures. These results suggest that biofilm formation is an important
      factor in the production of antimicrobial compounds by these 2 strains, and
      roller bottle cultivation also allowed production of these compounds to be
      increased. The methodology used here has the potential to allow increased
      production of useful secondary metabolites such as antibiotics from marine
      epibiotic bacteria.

PMID- 14961248
TI  - Genetic diversity within and among feral populations and domesticated strains of
      the guppy (Poecilia reticulata) in Singapore.
AB  - Genetic variability within and among feral populations and cultured strains of
      the guppy (Poecilia reticulata) was investigated by random amplification of
      polymorphic DNA (RAPD) fingerprinting. Feral guppies were collected from 6
      isolated populations (BT, Bukit Timah; NS, Nee Soon; TS, Tuas; MF, Mount Faber;
      KR, Kranji; LI, laboratory-inbred feral line), while the Tuxedo and Green
      Variegated strains were sampled from 2 guppy farms in Singapore. Pairwise genetic
      distances analyzed by unweighted pair-group method with arithmetic means revealed
      distinct clustering of guppy individuals into their respective populations and
      strains. Percentage polymorphic loci ranged from 54.96% (TS) to 68.70% (KR),
      while average heterozygosity ranged from 0.220 (GV) to 0.271 (KR). In contrast,
      TS guppies had the highest (0.850) intrapopulation genetic similarity (S),
      whereas KR had the lowest (0.781). Among populations and strains, S ranged from
      0.703 (between GV and LI) to 0.809 (between NS and MB). The GV strain S was
      closer to TX (0.784) than to the feral guppies. Bootstrapped genetic distance
      trees depicted 3 major nodes comprising BT-TS, NS-MF, and TX-GV. Principal
      coordinate analysis also differentiated the 6 feral populations from the 2
      cultured strains.

PMID- 14961249
TI  - Gene expression of Na+-K+-ATPase alpha 1 and alpha 3 subunits in gills of the
      teleost Oreochromis mossambicus, adapted to different environmental salinities.
AB  - The objective of the present study was to test the hypothesis that fish gills can
      express more than one isoform of the Na+-K+-ATPase a subunit responsible for ion
      regulation in seawater and freshwater environments. Using rapid amplification of
      complementary DNA ends (RACE), we cloned and sequenced full-length cDNAs encoding
      Na+-K+-ATPase alpha 1 and alpha 3 subunits of tilapia (Oreochromis mossambicus).
      Clone TG33 is 3390 bp in length and encodes a polypeptide of 1023 amino acids,
      while clone TH3 is 3581 bp in length and encodes a protein of 1010 amino acids.
      Clones TG33 and TH3 showed 91% and 88% identities at the amino acid level with
      previously described animal Na+-K+-ATPase alpha 1 and alpha 3 subunits,
      respectively. Northern blot and reverse transcriptase polymerase chain reaction
      analyses indicated that the alpha 1 subunit is expressed predominantly in kidney
      and intestine, while the alpha 3 subunit is expressed mainly in brain and heart.
      However, lower levels of expression of both genes were detected in other tissues
      such as gill, spleen, and testis. The amounts of both alpha 1 and alpha 3 subunit
      messenger RNA in gill tissue increased with the level of environmental salinity.
      This provides direct evidence of enhanced transcription of N+-K+-ATPase alpha 1
      and alpha 3 subunit genes upon salinity challenge.

PMID- 14961250
TI  - Sequence and conservation of a rRNA and tRNAVal mitochondrial gene fragment from
      Penaeus californiensis and comparison with Penaeus vannamei and Penaeus
      stylirostris.
AB  - Penaeus californiensis is an important species for shrimp fisheries in the
      Pacific Ocean and has recently been described as a potential cultured species,
      mainly through the winter season in subtropical regions. A fragment of the
      mitochondrial 12S rRNA-tRNAVal-16S rRNA genes from P. californiensis was
      sequenced and compared with the corresponding regions from Penaeus vannamei and
      Penaeus stylirostris. Purified mitochondrial DNA was used for polymerase chain
      reaction amplification with primers for 12S and 16S rRNA genes. A 1379 +/- 1-bp
      fragment was obtained, including 90% 16S rRNA, tRNAVal, and a portion of 12S
      rRNA, cloned, and sequenced. Genetic distances were calculated according to the
      Kimura 2-parameter distance model, and maximum-likelihood analysis was applied
      with 1000 bootstrap replications. Sequence identity of P. californiensis with
      both P. vannamei and P. stylirostris was 0.88, while for P. vannamei and P.
      stylirostris the identity was 0.92. Maximum-likelihood analysis grouped P.
      vannamei and P. stylirostris separately from P. californiensis.

PMID- 14961252
TI  - Complete mitochondrial DNA sequence of Tigriopus japonicus (Crustacea: Copepoda).
AB  - The complete nucleotide sequence of the mitochondrial genome was determined for a
      harpacticoid copepod, Tigriopus japonicus (Crustacea), using an approach that
      employs a long polymerase chain reaction technique and primer walking. Although
      the genome (14,628 bp) contained the same set of 37 genes (2 ribosomal RNA, 22
      transfer RNA, and 13 protein-coding genes) as found in other metazoan animals,
      none of the previously reported gene orders were comparable to that of T.
      japonicus. Furthermore, all genes were encoded on one strand, unlike the
      mitochondrial genomes of most metazoan animals. Size reductions were notable for
      tRNA and rRNA genes, resulting in one of the smallest mitochondrial genomes in
      the arthropod lineage. Although it appears that such large-scale gene
      rearrangements have occurred in the ancestral species of T. japonicus, none of
      the proposed mechanisms parsimoniously account for this eccentric gene
      arrangement.

PMID- 14961251
TI  - A marine strain of flavobacteriaceae utilizes brown seaweed fucoidan.
AB  - Fucoidan, a mixture of sulfated fucose-containing polysaccharides, was prepared
      from Kjellmaniella crassifolia (class Phaeophyceae, order Laminariales, family
      Laminariaceae) with a yield of about 3.8% dry weight. To isolate enzymes that
      degrade fucoidan, we first screened marine bacteria for their ability to utilize
      fucoidan, and isolated one strain of Flavobacteriaceae from seawater that could
      do this. Phylogenetic analysis of the 16S ribosomal DNA sequence suggested that
      this strain appeared to belong to a new genus, and was tentatively named
      Fucobacter marina. The strain utilized L-fucose (17%), D-mannose (91%), D
      galactose (46%), and D-glucuronic acid (66%) in the fucoidan from K. crassifolia.
      The strain partially utilized fucoidan from 2 other seaweeds that belong to the
      order Laminariales, Undaria pinnatifida (10%) and Lessonia nigrescens (48%).

PMID- 14961253
TI  - Isolation and characterization of tetranucleotide microsatellites from Atlantic
      haddock (Melanogrammus aeglefinus).
AB  - Five tetranucleotide microsatellite loci developed from Atlantic haddock
      (Melanogrammus aeglefinus) are presented. Loci were isolated using a modified
      magnetic bead-hybridization selection procedure that enriched for tetranucleotide
      microsatellites. Loci were polymorphic (3-99 alleles per locus; mean, 33.2) and
      exhibited high levels of observed heterozygosity (0.07-0.99; mean, 0.73) in a
      sample of 70 haddock collected from the Scotian Shelf in the Northwest Atlantic
      Ocean. Primer sets for 5 tetranucleotide microsatellites, originally developed
      from cod (Gmo34), were also tested in Atlantic haddock; one pair yielded readily
      detectable product and was variable in the population assayed (29 alleles;
      heterozygosity, 0.96). These loci are suitable for kinship analyses in
      aquaculture-related applications, and are potentially useful for resolving
      population structure in the wild.

PMID- 14961254
TI  - Multivariate optimization of polymerase chain reaction for microbial community
      analysis.
AB  - A multivariate regression, partial least square (PLS) approach was used to
      optimize a polymerase chain reaction (PCR) method for mixed communities. This
      approach, in contrast to univariate ones, provided information on the relative
      influence of the different factors to be optimized, as well as the interactions
      between factors. Models that predicted the outcome of further optimization were
      constructed from the initial experiments and verified experimentally. The models
      constructed were able to predict the outcome of a second set of experiments with
      high accuracy. PCR-amplification of DNA from environmental samples is often the
      first step in microbial community fingerprinting. Inhibitors and low cell numbers
      in the samples can cause problems with yield, for which compensation is normally
      made by increasing the number of cycles in the PCR-amplification reaction.
      Increasing the number of cycles, however, can cause other problems such as
      heteroduplex formation and increased bias. To avoid these problems the effects of
      different times of denaturing, annealing, and extension on yield were
      investigated for 2 different samples, one that consisted of a mixture of 9
      laboratory strains, and one that represented the microbial community from the
      surface of the red alga Delisea pulchra. The multivariate approach showed, in
      addition to the successful optimization of yield, that the different factors
      affected the PCR depending on sample type. Annealing time had the largest effect
      on yield for the mixture of laboratory strains, whereas extension time was most
      important for the D. pulchra community. We suggest that multivariate optimization
      is a useful tool for PCR optimization and can be used irrespectively of the
      particular factors that are being investigated.

PMID- 14961255
TI  - Antifouling activities of N-substituted imides: antimicrobial activities and
      inhibition of Mytilus edulis phenoloxidase.
AB  - In the search for novel biodegradable antifouling agents, a series of imides (N
      substituted maleimides and succinimides) have been synthesized. A large majority
      of N-substituted maleimides and succinimides showed an antimicrobial activity
      toward gram-positive and gram-negative bacteria and fungi of marine origin with
      minimal inhibition concentrations in the range of 6 to 24 microg/ml. The imides
      with an alkyl substituent showed higher activities than aromatic analogues, but
      structure-activity relationships were not clearly established. Some compounds
      were powerful inhibitors of Mytilus edulis phenoloxidase. This inhibition was
      noncompetitive as demonstrated with 2 maleimides, a 3-acetoxy succinimide and a
      succinimide. Thus, this family of products has potential interest as antifouling
      agents.

PMID- 14961256
TI  - Different temporal expressions of Tilapia (Oreochromis mossambicus) insulin-like
      growth factor-I and IGF binding protein-3 after growth hormone induction.
AB  - In vertebrates the insulin-like growth factor-I (IGF-I) is well recognized for
      its important roles in prenatal and postnatal processes. Liver is the major
      endocrine organ in mammals to produce IGF-I and its modulators, the insulin-like
      growth factor binding proteins (IGFBPs), which form a binary complex with IGF-I
      in circulation or in extracellular fluid. In the complex, IGFBP-3 accounts for
      the majority of IGFBPs that interact with IGF-I in circulation. To date, we know
      little of fish IGF-I regulation at the gene or protein level. In this preliminary
      experiment, we isolated tilapia IGFBP-3 complementary DNA sequence by degenerate
      polymerase chain reaction cloning. This identified clone contained a partial open
      reading frame of 635 bp and lacked both 5' and 3' end cDNA sequence information.
      The deduced 211 amino acid residues shared approximately 50% identity with
      mammalian counterparts. This tilapia IGFBP-3 transcript was expressed in every
      tissue examined with the highest level found in liver. In a growth hormone time
      course experiment, both IGF-I and IGFBP-3 message levels increased sharply, and
      after 24 hours of injection, IGF-I and IGFBP-3 was increased 1.97 and 2.15 fold,
      respectively. The relative message ratio of IGF-I to IGFBP-3 was 1.58, 1.09,
      0.94, 0.91, and 0.92 for 3, 6, 9, 12, and 24 hours, respectively. After 9 hours
      of treatment, the IGF-I/IGFBBP-3 message ratio maintained a constant value of
      approximately 0.9 throughout the experiment. This is the first report to
      demonstrate a fish counterpart of IGFBP-3 at the cDNA level and its message
      expression ratio with IGF-I under growth hormone induction.

PMID- 14961257
TI  - Gene expression of insulin-like growth factor-I receptor and p53 suppressor
      during zebrafish (Danio rerio) embryogenesis.
AB  - In vertebrates insulin-like growth factors (IGFs) regulate important cellular
      activities involving proliferation, differentiation, and antiapoptosis and their
      biological activities are mediated through the insulin-like growth factor-I
      receptor (IGF-IR). To understand the functions of IGF-IR in zebrafish
      embryogenesis, the polymerase chain reaction (PCR) cloning technique was applied
      to isolate the IGF-IR gene. A 5'-truncated 3285-nucleotide zebrafish IGF-IR
      sequence was assembled from 3 overlapping clones. This contained a partial coding
      region of 1550 nucleotides and a 1735-nucleotide 3' untranslated region. The
      deduced 515 amino acid residues included the conserved kinase domain and shared
      60.9%, 61.1%, and 59.9% homology to human, mouse, and frog, respectively. To
      understand the relationship of IGF-IR with p53 suppressor gene during
      embryogenesis, expression of both genes was analyzed in parallel by
      semicompetitive reverse transcriptase PCR and whole-mount in situ hybridization.
      This analysis indicated that messenger RNA of both genes was of maternal origin,
      but the p53 suppressor mRNA was relatively more abundant than the IGF-IR message
      in most of the developmental stages, except possibly at 28 hours
      postfertilization. At this stage the IGF-I receptor message was highly expressed
      and visible in whole internal organ regions by whole-mount in situ hybridization,
      while p53 message was concentrated in the head portion and barely detectable in
      the trunk portion. The results suggest that IGF-IR and p53 mRNA are expressed at
      different places and different times. However, the temporal and spatial
      relationship of IGF-IR and its relationship to p53 suppressor protein during
      developmental processes remain unknown.

PMID- 14961258
TI  - Functional analysis of the proximal promoter regions of fish rhodopsin and myf-5
      genes using transgenesis.
AB  - Little is known about the cis-acting elements controlling transcriptional
      activities of fish rhodopsin and myf-5 genes. Transgenic medaka and zebrafish
      were used to characterize promoters of carp (Cyprinus carpio) rhodopsin gene
      (cRh) and zebrafish (Danio rerio) myf-5 gene (myf-5), respectively. Transgenic
      medaka carrying different lengths of cRh upstream fragments fused with enhanced
      green fluorescence protein (EGFP) gene revealed several functional regions. Both
      upstream regions from -1261 to -163 bp (-1261/-163) and -163/-138 contributed to
      enhance the retina-specific activities of cRh. The cNRE (-75/-63) and CSE (-52/
      46) motifs located at the cRh proximal promoter were sufficient to drive the
      transgene expressed in retinae. The -73/-68 within cNRE was also proved to be
      essential for the integrity of the minimal cis-regulatory elements. Regarding the
      myf-5, transgene expression in zebrafish embryos injected with different deletion
      fragments of zebrafish myf-5 upstream sequences showed that the -2776/-2456 and 
      1046/-844 regions contributed to the enhancer function. The -290/-154 region
      might be involved in controlling the translocation of progenitor muscle cells.
      Moreover, the upstream -82/-1 region was identified as a minimal promoter
      required for somite-specific expression. The -82/-62 region was the most critical
      sequence for myf-5 specificity.

PMID- 14961259
TI  - Gene knock-down in rainbow trout embryos using antisense morpholino
      phosphorodiamidate oligonucleotides.
AB  - Gene knock-down technology using antisense molecules has many applications for
      studying gene function, disrupting undesirable genetic traits, as well as
      providing effective therapy for a number of viral diseases. Encouraged by these
      applications, we developed a gene knock-down technique to interfere with gene
      expression using transgenic rainbow trout expressing the green fluorescent
      protein (GFP) gene as a model. One of the antisense morpholino phosphorodiamidate
      oligonucleotides (AMOs) used in this study (AtGFP-1) was 25 nucleotides in length
      and localized against codons 2 to 8 of GFP messenger RNA. Microinjection of AtGFP
      1 into the blastodisc of fertilized eggs decreased the level of GFP gene
      expression in a dose-dependent manner, A comparison of the effects of various
      doses of AtGFP-1 suggested that 10 ng of AtGFP-1 was the optimal concentration in
      that it interfered with specific gene expression without being strongly toxic to
      trout embryos. Conversely, morpholino phosphorodiamidate oligonucleotides with
      the inverted AtGFP-1 sequence, which cannot bind to the target mRNA, did not
      inhibit GFP gene expression. AtGFP-1 did not affect the expression of nontargeted
      genes such as the skeletal muscle actin and foreign lacZ genes. These results
      also indicate that AtGFP-1 interfered with the expression of only the targeted
      gene. Western blot and reverse transcriptase polymerase chain reaction analyses
      revealed that the amount of GFP protein drastically decreased whereas the mRNA
      level was not affected by AtGFP-1, suggesting that AtGFP-1 blocked specific gene
      function at the translational level. Further, this gene inhibition persisted
      until the hatching stage. Another AMO, which was localized against the junction
      region between the 5? untranslated region and the starting codon of GFP mRNA
      (AtGFP-2), also caused inhibition effects. Thus AMOs can have potent and specific
      gene knock-down effects in trout embryos. This technology may be useful for
      examining the roles of selected genes and disrupting their expression during
      embryonic development of salmonid fish.

PMID- 14961260
TI  - Pathogenesis of gastroenteritis caused by Vibrio carchariae in cultured marine
      fish.
AB  - Serious mortality among the cultured grouper Epinephelus coioides, characterized
      by a swollen intestine containing yellow fluid (gastroenteritis), occurred in
      1993 in Taiwan. A bacterium isolated from the intestinal fluid and head kidney of
      moribund groupers was identified as Vibrio carchariae. Since then, the same
      Vibrio species has also been isolated from moribund black sea bream Acanthopagrus
      schlegeli, yellowfin sea bream A. latus, Japanese sea bass Lateolabrax japonicus,
      and red drum Sciaenops ocellatus suffering from the same syndrome. Each isolate
      was virulent to the respective fish. Recently, a similar syndrome, flounder
      infectious necrotizing enteritis, also caused by V. carchariae in summer flounder
      Paralichthys dentatus, was reported in Rhode Island. The extracellular products
      (ECPs) of V. carchariae strains EmI82KL (from grouper), Rd (from red drum), and
      SfUSA (from summer flounder, U.S.A.) were virulent to the grouper or red drum. A
      33-kDa serine protease partially purified from the ECP of strain EmI82KL was
      lethal to the fish. All the moribund or killed fish exhibited gastroenteritis
      except those killed within 12 hours. This report is the first to show that
      intraperitoneal injection of the ECP or protease in the fish is virulent and can
      reproduce gastroenteritis. The serine protease was suggested as a major toxin in
      the grouper or red drum secreted by V. carchariae.

PMID- 14961261
TI  - Crustins, homologues of an 11.5-kDa antibacterial peptide, from two species of
      penaeid shrimp, Litopenaeus vannamei and Litopenaeus setiferus.
AB  - The response of crustaceans to pathogens is believed to depend solely on innate,
      nonadaptive immune mechanisms, including phagocytosis, encapsulation, clotting,
      and a variety of soluble antimicrobial activities. Arthropod antimicrobial
      peptides, while characterized primarily from insects, also have been isolated
      from crustaceans. Expressed sequence tag analysis of hemocyte complementary DNA
      libraries from 2 species of shrimp, Litopenaeus vannamei and Litopenaeus
      setiferus, revealed transcripts with strong sequence similarity to an 11.5-kDa
      antibacterial peptide (crustin Cm1) found in Carcinus maenas. Crustins were also
      observed to contain motifs common to proteinase inhibitors. Analysis of these
      cDNA libraries yielded at least 3 different isoforms of this peptide in L.
      vannamei (crustin Lv1-Lv3) and 3 in L. setiferus (crustin Ls1-Ls3). Further
      analysis of a second L. vannamei cDNA library revealed the presence of 3 more
      possible isoforms (crustin Lv4-Lv6), which differed from those seen in the first
      L. vannamei cDNA library. Genomic Southern blot analysis revealed a complex
      family of crustin-related sequences. However, full-length crustin appears to be
      encoded by a much more restricted subset of sequences within this family.

PMID- 14961262
TI  - Effect of cecropin B and a synthetic analogue on propagation of fish viruses in
      vitro.
AB  - Cecropins and other natural antimicrobial peptides are widely distributed in
      animals from insects to mammals. These proteins have been shown to be major
      constituents of the innate immune systems of animals for nonspecific defense of
      the host against various bacteria and parasites. Therefore, exploitation of this
      natural innate defense system may lead to the development of effective methods
      for protecting fish from invasion by microbial pathogens. Recently, we have
      demonstrated that the introduction of cecropin transgenes into Japanese medaka
      (Oryzias latipes) conferred resistance to infection by fish bacterial pathogens.
      Aside from a few reports documenting the antiviral effect of antimicrobial
      peptides including cecropins against mammalian viruses, there is no evidence for
      the effect of these peptides against fish viruses. In this article we present
      results of in vitro characterization of native cecropin B and a synthetic
      analogue, CF17, against several important fish viral pathogens--namely,
      infectious hematopoietic necrosis virus (IHNV), viral hemorrhagic septicemia
      virus (VHSV), snakehead rhabdovirus (SHRV), and infectious pancreatic necrosis
      virus (IPNV). Upon coincubation of these peptides and viruses, the viral titers
      yielded in fish cells were reduced from several fold to 104-fold. Direct
      disruption of the viral envelope and disintegration of the viral capsids may be
      involved in the inhibition of viral replication by the peptides. Results of our
      studies demonstrate the potential of manipulating antimicrobial peptide genes by
      transgenesis to combat viral infection in fish.

PMID- 14961263
TI  - Gene transfer to fish cells by attenuated invasive Escherichia coli.
AB  - Genetic immunization has proved effective in a number of applications including
      vaccination of rainbow trout (Oncorhynchus mykiss) against the fish pathogen
      infectious hematopoietic necrosis virus. However, injection vaccines, especially
      in aquaculture, are not as desirable as oral or immersion dosing schemes. In this
      report we present evidence that attenuated invasive Escherichia coli can infect
      and deliver plasmid DNA to salmonid fish cells.

PMID- 14961264
TI  - Production of transgenic medaka with increased resistance to bacterial pathogens.
AB  - Cecropins, first identified in silk moth (Hyalophora cecropia), are a group of
      antimicrobial peptides with bactericidal activity against a broad spectrum of
      bacteria. In this study we investigated whether (1) this group of antimicrobial
      peptides could exhibit bactericidal activity toward known fish bacterial
      pathogens and (2) expression of cecropin transgenes in transgenic medaka (Oryzias
      latipas) could result in increasing resistance of the transgenic fish to
      infection by fish bacterial pathogens. Cecropin gene construct containing silk
      moth preprocecropin B, procecropin B and cecropin B, and porcine cecropin P1
      driven by a cytomegalovirus (CMV) promoter were transfected into chinook salmon
      embryonic cells (CHSE-214) by lipofection, and the resulting permanent
      transformants were collected. In an "inhibition zone" assay medium isolated from
      each transformant exhibited strong bactericidal activity toward known fish
      bacterial pathogens such as Pseudomonas fluorescens, Aeromonas hydrophila, and
      Vibrio anguillarum. The same cecropin transgene constructs were introduced into
      newly fertilized medaka eggs by electroporation to produce transgenic fish. About
      40% to 60% of the embryos survived from electroporation, and about 5% to 11% of
      the surviving fish were shown to contain cecropin transgenes by polymerase chain
      reaction analysis of genomic DNA samples isolated from presumptive transgenic
      fish. These P1 transgenic fish were used as founder stocks, and following
      generations of successive breeding, a total of 20 F2 families of transgenic fish
      were established. Expression of cecropin transgenes was detected in the F2
      transgenics by reverse transcriptase polymerase chain reaction analysis. Southern
      blot analysis of genomic DNA isolated from different F2 fish showed that cecropin
      transgenes were integrated into the genomes of F2 transgenic fish. To determine
      whether transgenic fish carrying cecropin transgenes could exhibit resistance to
      infection by known fish bacterial pathogens, F2 transgenic fish from different
      families and control fish were challenged with P. fluorescens and V. anguillarum
      at a 60% lethal dose. Challenge studies showed that while about 40% of the
      control fish were killed by both pathogens, only up to 10% of the F2 transgenic
      fish were killed by P. fluorescens and about 10% to 30% by V. anguillarum. These
      results clearly showed that the transgenic medaka carrying cecropin transgenes
      had acquired elevated resistance to bacterial infection.

PMID- 14961265
TI  - Survival of F2 transgenic common carp (Cyprinus carpio) containing pRSVrtGH1
      complementary DNA when subjected to low dissolved oxygen.
AB  - The survival and tolerance of F2 transgenic common carp (Cyprinus carpio)
      containing pRSVrtGH1 complementary DNA were compared with nontransgenic (control)
      common carp when subjected to low dissolved oxygen. The tolerance of low oxygen
      was evaluated in 8 families of common carp in rectangular tanks (3 x 1 x 1 m).
      The absolute mean percentage of survival of transgenic common carp subjected to
      low oxygen (0.4 mg/L) was higher (P <0.05) than that of control carp in 2 of the
      8 families of common carp tested; however, the overall means for all families of
      transgenic and control carp were not different (P > 0.05). When oxygen tolerance
      was measured in time to death rather than absolute survival or mortality, the
      growth hormone transgenic common carp had a longer group mean (P <0.05) than did
      controls. The mean survival time in minutes for the transgenic genotype was
      greater (P <0.05) in 5 of the 8 families assessed. Transgenic common carp in some
      families had higher percentage and longer times of survival than control common
      carp when subjected to low oxygen. The definition of tolerance of low oxygen and
      how it is measured is important, and can affect interpretation of results. The
      pleiotropic effect of pRSVrtGH1 cDNA on superior survival of low oxygen in common
      carp has important implications for intensive fish culture.

PMID- 14961266
TI  - Production of transgenic silver sea bream (Sparus sarba) by different gene
      transfer methods.
AB  - We have been interested in developing convenient mass gene transfer methods for
      producing strains of silver sea bream (Sparus sarba) with superior genetic traits
      for aquaculture. A transgene construct carrying rainbow trout growth hormone
      (rtGH) complementary DNA driven by a common carp b-actin promoter was introduced
      into silver sea bream by electroporating the sperm with the rtGH transgene and
      using the treated sperm to fertilize eggs stripped from mature females. The
      presence of the GH transgene in presumptive transgenic individuals was detected
      by polymerase chain reaction (PCR) analysis. Between 56% and 70% of the animals
      carried the GH transgene. We refer to this method as sperm-mediated gene transfer
      (SMGT). Since the handling stress of stripping gametes from female sliver sea
      bream brood fish could cause severe mortality, an alternative gene transfer
      method would be highly desirable. We developed a liposome-based method to
      transfer the GH transgene into the fish. This method, referred as testis-mediated
      gene transfer (TMGT), involves injecting the liposome-transgene mixture into the
      gonads of male sea bream at least 48 hours before spawning. The males were mated
      to reproductively active females, and fertilized eggs were collected for further
      incubation. Between 59% and 76% of the hatched fry were found by PCR analysis to
      carry the rtGH transgene. The efficiency of gene transfer was improved more than
      80% by injecting multiple doses of the liposome-transgene mixture into the gonads
      of treated males. Results of Southern blot analysis of DNA isolated from PCR
      positive animals showed that the transgene was integrated into the host genome
      and could be transmitted to its offspring. The rtGH transgene was expressed in
      many of the rtGH-transgenic fish. Several P1 GH-transgenic silver sea bream
      exhibited significant growth enhancement compared with nontransgenic controls.
      Our studies showed that faster-growing silver sea bream could be produced by a
      variety of mass gene transfer technologies. These gene transfer technologies
      would be of great value to aquaculture.

PMID- 14961267
TI  - Enhanced bacterial disease resistance of transgenic channel catfish Ictalurus
      punctatus possessing cecropin genes.
AB  - The cecropin B gene from the moth Hyalophora cecropia, driven by the
      cytomegalovirus promoter, was transferred to the channel catfish Ictalurus
      punctatus. Transgenic individuals (P1) were mated to produce individuals (F1)
      that exhibited enhanced disease resistance and survival when challenged with
      pathogenic bacteria. During the epizootic of Flavobacterium columnare in an
      earthen pond, the percentage of transgenic individuals containing preprocecropin
      B construct that survived (100%) was significantly greater (P <0.005) than that
      of nontransgenic controls (27.3%). Also, when challenged in tanks with
      Edwardsiella ictaluri, the causative agent of enteric septicemia of catfish, the
      percentage of transgenic individuals containing catfish IG leader cecropin B
      construct that survived (40.7%) was significantly greater (P <0.01) than that of
      nontransgenic controls (14.8%). There were no pleiotropic effects of the
      transgenes, and growth rates of the transgenic and nontransgenic siblings were
      not different (P > 0.05). Inheritance of the transgene by the F1 generation,
      20.2% to 30.7% was typical of that in studies with transgenic channel catfish.

PMID- 14961269
TI  - Antifouling potential of some marine organisms from India against species of
      Bacillus and Pseudomonas.
AB  - Crude methanolic extracts of 37 marine organisms (16 species of flora, 21 species
      of fauna) were screened for antibacterial properties against 5 strains of
      bacteria isolated from marine environments. Of these, 10 plant and 9 animal
      extracts exhibited antibacterial activity against at least one bacterial strain.
      The extracts of 6 species were active against all the strains: i.e.,
      Stoechospermum marginatum (brown algae), Cymodocea rotundata (seagrass), Petrosia
      sp. and Psammaplysilla purpurea (sponges), Sinularia compressa (soft coral), and
      Cassiopeia sp. (jellyfish). Among the plants, Padina tetrastromatica (brown
      algae) extract exhibited significant activity (9-11-mm inhibition zone at 500
      microg per 6-mm disc) against Bacillus pumilus and Pseudomonas vesicularis, while
      the extracts of Petrosia, Psammaplysilla, and Cassiopeia were strongly active (11
      13-mm inhibition zone at 500 microg per 6-mm disc) against B. circulans and P.
      putida. It was further confirmed that the attachment of bacterial strains on
      glass slides was inhibited remarkably with increasing concentrations of
      bioextracts of Petrosia sp. and Psammaplysilla purpurea. The present findings
      could form the basis for exploring the antibacterial potential of bioactive
      molecules from some of the marine organisms that exhibited moderate to strong
      antibacterial properties.

PMID- 14961268
TI  - Isolation and characterization of 2-nitroimidazole produced by Streptomyces
      species as an inhibitor of both carbonic anhydrase and shell formation in the
      barnacle Balanus amphitrite.
AB  - Carbonic anhydrase is thought to be involved in the process of calcium carbonate
      deposition in calcified tissues of many organisms. Barnacles form hard calcified
      shells for protection against predation, and represent a class of marine-fouling
      animals. In order to inhibit barnacle growth by inhibiting shell formation, we
      searched for carbonic anhydrase inhibitors from microbial secondary metabolites.
      A simple assay for assessing carbonic-anhydrase-inhibiting activity was
      developed. Screening of many microorganisms isolated from soil with this assay
      resulted in a microbial strain that produced a carbonic anhydrase inhibitor. This
      strain was identified as Streptomyces eurocidicus mf294. The inhibitor was
      isolated through 4 purification steps and identified as 2-nitroimidazole on the
      basis of spectroscopic data. 2-Nitroimidazole inhibited barnacle carbonic
      anhydrase dose-dependently and complete inhibition was reached at the
      concentration of 1 x 10(-5) M. 2-Nitroimidazole did not affect settlement or
      metamorphosis of barnacle larvae, but inhibited shell formation at concentrations
      higher than 1 x 10(-4) M. These findings strongly support the idea that carbonic
      anhydrase is involved in calcification.

PMID- 14961270
TI  - Genetic identification of grey mullet species (Mugilidae) by analysis of
      mitochondrial DNA sequence: application to identify the origin of processed ovary
      products (bottarga).
AB  - Mitochondrial DNA sequencing was used to identify and distinguish four species of
      commercially important Mediterranean grey mullets. Partial cytochrome b and D
      loop sequences were obtained from the four fish species, and these were used to
      perform phylogenetic analysis and to determine species-specific DNA fingerprints.
      Species-specific amplification primers were designed from these fingerprints, and
      these were used to characterize the species origin of several samples of
      commercial, processed mullet ovary products. In addition to differentiating
      between food products from different species, this method is also sensitive
      enough to distinguish food products from mullets of the same species from
      different regions.

PMID- 14961271
TI  - In situ microspatial imaging using two-photon and confocal laser scanning
      microscopy of bacteria and extracellular polymeric secretions (EPS) within marine
      stromatolites.
AB  - The combination of a hydrophilic embedding resin, Nanoplast, with fluorescent
      probes, and subsequent imaging using two-photon and confocal laser scanning
      microscopy (2P-LSM and CLSM) has allowed in imaging of the in situ microspatial
      arrangements of microbial cells and their extracellular polymeric secretion (EPS)
      within marine stromatolites. Optical sectioning by 2P-LSM and CLSM allowed
      imaging of endolithic cyanobacteria cells, Solentia sp., seen within carbonate
      sand grains. 2P-LSM allowed very clear imaging with a high resolution of bacteria
      using DAPI, which normally require UV excitation and reduced photo-bleaching of
      fluorescent probes.

PMID- 14961272
TI  - Identification of two distinct molt-inhibiting hormone-related peptides from the
      giant tiger prawn Penaeus monodon.
AB  - Six peptides belonging to the crustacean hyperglycemic hormone (CHH) family were
      isolated from extracts of the sinus glands of the giant tiger prawn Penaeus
      monodon by reverse-phase high-performance liquid chromatography. These were
      designated Pem-SGP-A to Pem-SGA-F (Pem, Penaeus monodon; SGP, sinus gland
      peptide) and their amino-terminal amino acid sequences were analyzed. Five of the
      6 peptides (Pem-SGP-A, -B, -D, -E, and -F) exhibited similar amino acid sequences
      to those of CHH peptides that had been characterized previously from the same
      prawn species by the other research groups, while 1 peptide (Pem-SGP-C) exhibited
      a novel sequence. Pem-SGP-C showed sequence similarity to known putative molt
      inhibiting hormones (MIHs), particularly to an MIH from the kuruma prawn Penaeus
      japonicus, and less similarity to the CHHs determined thus far. Two similar
      complementary DNAs encoding Pem-SGP-C were cloned and found to encode very
      similar but distinct peptides, which were named Pem-SGP-C1 and Pem-SGA-C2. The
      open reading frame of each cDNA consisted only of a signal peptide and an MIH
      like peptide. We also cloned 2 corresponding genes, both of which consisted of 3
      exons and 2 introns. Analyses by reverse transcriptase polymerase chain reaction
      demonstrated that both Pem-SGP-C1 and Pem-SGP-C2 transcripts were detected only
      in cDNA synthesized using total RNA from the eyestalk but not in that from brain,
      thoracic ganglia, abdominal ganglia, abdominal muscle, hepatopancreas, or heart
      tissue of P. monodon.

PMID- 14961273
TI  - Use of AFLP analyses to assess genetic variation in Morone and Thunnus species.
AB  - The amplified fragment length polymorphism (AFLP) technique was used to assess
      genetic variation across the genera of 2 Morone and 3 Thunnus species. The AFLP
      profiles from 23 primers revealed higher levels of polymorphism in each of 3
      Thunnus species than in either of the 2 Morone species. However, extensive
      variation (20 of 23 primers) was observed between the 2 Morone species, but much
      less variation was observed among the 3 Thunnus species. In addition, comparisons
      of banding patterns indicated that albacore is divergent from both Atlantic
      northern bluefin tuna and yellowfin tuna. This result is consistent with the
      findings of several previous studies employing either allozymes or mitochondrial
      DNA. Overall, these results demonstrate that AFLP is a useful technique for the
      assessment of both intraspecies and interspecies variation of fish. Furthermore,
      the species-specific patterns produced by AFLP can be used for the identification
      of closely related species.

PMID- 14961274
TI  - Generation of two-color transgenic zebrafish using the green and red fluorescent
      protein reporter genes gfp and rfp.
AB  - Two tissue-specific promoters were used to express both green fluorescent protein
      (GFP) and red fluorescent protein (RFP) in transgenic zebrafish embryos. One
      promoter (CK), derived from a cytokeratin gene, is active specifically in skin
      epithelia in embryos, and the other promoter (MLC) from a muscle-specific gene
      encodes a myosin light chain 2 polypeptide. When the 2 promoters drove the 2
      reporter genes to express in the same embryos, both genes were faithfully
      expressed in the respective tissues, skin or muscle. When the 2 fluorescent
      proteins were expressed in the same skin or muscle cells under the same promoter,
      GFP fluorescence appeared earlier than RFP fluorescence in both skin and muscle
      tissues, probably owing to a higher detection sensitivity of GFP. However, RFP
      appeared to be more stable as its fluorescence steadily increased during
      development. Finally, F(1) transgenic offspring were obtained expressing GFP in
      skin cells under the CK promoter and RFP in muscle cells under the MLC promoter.
      Our study demonstrates the feasibility of monitoring expression of multiple genes
      in different tissues in the same transgenic organism.

PMID- 14961275
TI  - Bioluminescence of Aequorea macrodactyla, a common jellyfish species in the East
      China Sea.
AB  - Studies of the bioluminescent mechanisms of jellyfish have been mainly confined
      to one species, Aequorea victoria. We describe the luminescent system of another
      species, Aequorea macrodactyla, which is commonly found in the warmer waters on
      the coastal region of East China Sea. The luminescent system of this species
      consists of a green fluorescent protein (GFP) and one or more aequorins. The GFP
      gene is 1042 bp. It encompasses a coding sequence of 717 bp organized as 3 exons,
      and it is predicted to specify a 27-kDa peptide, which shares 80% amino acid
      sequence identity with the GFP of A. victoria. The entire coding sequence was
      cloned into the pTO-T7 expression vector and expressed in Escherichia coli.
      Compared with GFP of A. victoria, the purified expressed protein exhibited an
      excitation peak at a higher wavelength of 476 nm and an emission peak at a lower
      wavelength of 496 nm, with a higher quantum yield of 1.0. The other photoprotein,
      aequorin, is encoded in a single open reading frame of 585 bp specifying a 23-kDa
      apoprotein. The gene was cloned in to the same expression vector and expressed in
      E. coli. The activity of the photoprotein was reconstituted by incubating the
      expressed apoprotein with coelenterazine f. In the presence of Ca(2+) the
      reconstituted aequorin exhibits an emission peak at 470 nm. The kinetics of
      regeneration and the photoactivities of the reconstituted aequorins of the 2
      species of jellyfish are similar. Nevertheless, Aequorea macrodactyla is expected
      to appear brighter and more "blue" than Aequorea victorea because of the
      differences in the photoactivity of their GFPs.

PMID- 14961276
TI  - Mitochondrial DNA sequence variation suggests the lack of genetic heterogeneity
      in the Adriatic and Ionian stocks of Sardina pilchardus.
AB  - A genetic stock structure analysis of 11 sardine samples from the Adriatic Sea
      and Ionian neighboring area was carried out through sequence variation analysis
      of a 307-bp cytochrome b gene fragment in order to identify self-recruiting units
      in the Adriatic Sardina pilchardus stock. The overall lack of genetic subdivision
      among samples detected by analysis of molecular variance, pairwise Phi(st)
      values, and the exact test of population differentiation indicates this sardine
      stock is part of a larger self-recruiting population whose boundaries are larger
      than the investigated area. This conclusion is in agreement with preliminary
      allozymic and mitochondrial DNA restriction fragment length polymorphism data,
      but contradicts the previous identification of 2 subpopulations of sardines in
      the Adriatic Sea argued on morphologic differences, which could be rather
      attributed to different hydrographic or ecologic conditions occurring in
      different areas of the Adriatic Sea. The reduced gene flow observed between
      Adriatic-Ionian and Spanish sardine geographic samples (P < 0.001) suggests that
      reproductively isolated populations of sardines may occur in the Mediterranean
      Sea.

PMID- 14961277
TI  - Rapid screening of a novel arrayed medaka (Oryzias latipes) cosmid library.
AB  - Medaka (Oryzias latipes) has many advantages for genetic and developmental
      studies. With recent advances in the genome analyses of other species, rapid
      accumulation of resources for medaka genomics is expected. In this study, we
      generated an arrayed medaka cosmid library from the HNI inbred strain, carrying a
      40-kb insert on average. The library consists of approximately 120,000 clones
      with a 6-fold genomic coverage. Cosmid clones can be screened within 2 days using
      standard polymerase chain reaction. Considering the advantage of the cosmid
      insert size and the compact genome size of the medaka, this library provides a
      powerful tool for future genome analyses.

PMID- 14961278
TI  - Characterization of surfactin-like cyclic depsipeptides synthesized by Bacillus
      pumilus from ascidian Halocynthia aurantium.
AB  - A marine bacterium (KMM 1364), identified as Bacillus pumilus, was isolated from
      the surface of ascidian Halocynthia aurantium. Structural analysis revealed that
      the strain KMM 1364 produced a mixture of lipopeptide surfactin analogs with
      major components with molecular masses of 1035, 1049, 1063, and 1077. The
      variation in molecular weight represents changes in the number of methylene
      groups in the lipid and/or peptide portions of the compounds. Structurally, these
      lipopeptides differ from surfactin in the substitution of the valine residue in
      position 4 by leucine, and have been isolated as two carboxy-terminal variants,
      with valine or isoleucine in position 7. As constituents of the lipophilic part
      of the peptides, only beta-hydroxy-C(15)-, beta-hydroxy-C(16)-, and a high amount
      of beta-hydroxy-C(17) fatty acid were determined.

PMID- 14961279
TI  - Screening of red algae filaments as a potential alternative source of
      eicosapentaenoic acid.
AB  - Lipids were extracted by a supercritical fluid extraction method from 10 species
      of filamentous red algae obtained from culture collections and their fatty acid
      compositions were determined. The fatty acid profiles of the 10 species were
      similar. The major fatty acids were 16:0, 20:4 omega 6 and 20:5 omega 3
      (eicosapentaenoic acid, EPA), which amounted to over 70% of the total fatty
      acids. The highest EPA content (29.8 mg/L), as a percentage of total fatty acids,
      was produced by Liagora boergesenii filaments, which has good potential for EPA
      mass production in pilot plants.

PMID- 14961280
TI  - Chronic salinity adaptation modulates hepatic heat shock protein and insulin-like
      growth factor I expression in black sea bream.
AB  - Black sea bream ( Mylio macrocephalus) hepatic heat shock proteins hsp90, hsp70,
      and hsp60 were found to be thermally and reversibly inducible as they were
      elevated 2.0, 3.2, and 2.1 fold, respectively, on acute heat shock and returned
      to pre-heat-shock levels after a 40-hour recovery period. To establish whether
      salinity plays a role in regulating heat shock protein (hsp) and insulin-like
      growth factor-I (IGF-I) expression in a euryhaline marine fish, we adapted groups
      of juvenile black sea bream to salinities of 50 ppt (hypersaline), 33 ppt
      (seawater), 12 ppt (isoosmotic), and 6 ppt (hypoosmotic) for 8 months. The lowest
      levels of hsps were found in fish reared in an isoosmotic salinity and the
      highest in those adapted to hypersaline and hypoosmotic salinities. Hepatic beta
      actin messenger RNA abundance remained unchanged in all groups during salinity
      adaptation, whereas IGF-I mRNA abundance was highest in isoosmotic adapted black
      sea bream. This study is the first report of an effect of salinity ranging from
      hypersaline to hypoosmotic on the expression of different hsp forms and IGF-I in
      fish, and the possible relationship between environmental salinity, hepatic IGF-I
      expression, and hsp regulation is discussed.

PMID- 14961282
TI  - Cloning and characterization of replication protein A p32 complementary DNA in
      zebrafish (Danio rerio).
AB  - Replication protein A (RPA) is a heterotrimeric single-stranded DNA-binding
      protein (70, 32, and 14 kDa) that is an essential component of the DNA
      replication fork. A complementary DNA encoding zebrafish RPA 32-kDa subunit was
      isolated by screening a zebrafish embryo lambda APII cDNA library with a human
      RPA p32 cDNA probe. The zebrafish RPA p32 cDNA consisted of 1097 bp encoding 272
      amino acid residues. The deduced amino acid sequence shows high similarity to
      mouse and human RPA p32. In vitro phosphorylation of zebrafish RPA protein by
      Cdc2 kinase was shown. A recombinant protein of zebrafish RPA p32 containing a
      short histidine tag at the NH(2)-terminus was overexpressed in Escherichia coli
      BL21(DE3) pLys using an inducible T7 expression system, and was purified by Ni
      NTA affinity chromatography. In this article, cloning of the zebrafish RPA p32
      cDNA is reported in relation to the study of DNA replication in fish.

PMID- 14961283
TI  - Gene transfer and cloning of flanking chromosomal regions using the medaka fish
      Tol2 transposable element.
AB  - For the ultimate purpose of developing genetic tools using the medaka fish Tol2
      transposable element, we examined whether it can transfer a marker gene into the
      fish genome and also be applied for cloning of chromosomal regions adjacent to
      insertion points. An internal region of Tol2 was removed and replaced with the
      green fluorescent protein (GFP) gene and a bacterial plasmid replication origin.
      This modified Tol2 clone was microinjected into fertilized eggs together with
      messenger RNA for the Tol2 transposase. The GFP gene was found to be integrated
      into chromosomes and transmitted to subsequent generations. Restriction enzyme
      digestion of genomic DNA of a transformant fish, followed by ligation and
      introduction into bacteria, produced a plasmid containing the entire element and
      flanking chromosomal regions. Sequencing analysis of this clone demonstrated
      transposition of the element in the germline of the first generation. Thus, the
      basic requirements for a gene transfer vector and gene tagging system were
      fulfilled.

PMID- 14961284
TI  - Development of rainbow trout microsatellite markers from repeat enriched
      libraries.
AB  - The efficiency of developing polymorphic microsatellite markers from 2 repeat
      enriched libraries was evaluated. Thirty-six polymorphic microsatellite markers
      were developed for rainbow trout, 27 of which were informative in a mapping
      family. The ability of each marker to amplify genomic DNA from other salmonids
      was also observed.

PMID- 14961286
TI  - Rapid identification of adult and naupliar stages of copepods using DNA
      hybridization methodology.
AB  - Larval stages of common marine invertebrates and their ecological roles within
      their respective communities are frequently ignored because they are hard to
      identify. Morphological characters are often insufficient to differentiate
      between genera, much less species. To overcome the obstacles associated with
      species identification of copepod larvae, we developed a microtiter plate-based
      hybridization assay. Species-specific probes based on rDNA sequences were bound
      to microplates and used to capture target DNA. A novel method of linking the
      probes to the plate with poly-T tail ensured the probes were positioned above the
      plate surface and available for hybridization; this significantly increased the
      sensitivity of the assay. Target DNA extracted from individual copepods was
      amplified with biotin-labeled primers. The labeled target DNA bound to the probe
      specific for that species and produced a colorimetric change in the assay. The
      assay can be rapidly performed on freshly caught or ethanol preserved samples and
      the results visually interpreted.

PMID- 14961285
TI  - Nucleotide sequences of ribosomal internal transcribed spacers and their utility
      in distinguishing closely related Perinereis polychaets (Annelida; Polychaeta;
      Nereididae).
AB  - Nucleotide sequences of a segment of the rRNA transcription unit spanning from
      the 3' end of the 18S rDNA to the 5' end of 28S rDNA were determined for four
      species of Perinereis polychaetes: P. aibuhitensis, P. floridana, and two
      undescribed species, Perinereis sp1 and sp2. The 5.8S rDNA sequences are
      identical among the four species. Intraspecific variability was low with the
      Kimura 2-parameter (K2P) distance, ranging from 0 to 0.0138 for ITS1 and 0 to
      0.0247 for ITS2. The interspecific nucleotide difference was significantly higher
      than those within species, with a mean K2P of 0.172 for ITS1 and 0.204 for ITS2,
      suggesting that comparisons of ITS regions can be used to evaluate the
      phylogenetic relationships among Perinereis species. Both neighbor-joining and
      parsimony analyses of ITS variability indicate a close relationship between the
      two undescribed species of Perinereis. These findings highlight the utility of
      the ITS sequence in conjunction with other morphological and ecological
      characters to delineate species boundaries among closely related polychaetes.

PMID- 14961287
TI  - Length and sequence variability in mitochondrial control region of the milkfish,
      Chanos chanos.
AB  - Extensive length variability was observed in the mitochondrial control region of
      the milkfish, Chanos chanos. The nucleotide sequence of the control region and
      flanking regions was determined. Length variability and heteroplasmy was due to
      the presence of varying numbers of a 41-bp tandemly repeated sequence and a 48-bp
      insertion/deletion (indel). The structure and organization of the milkfish
      control region is similar to that of other teleost fish and vertebrates. However,
      extensive variation in the copy number of tandem repeats (4-20 copies) and the
      presence of a relatively large (48-bp) indel, are apparently uncommon in teleost
      fish control region sequences reported to date. High sequence variability of
      control region peripheral domains indicates the potential utility of selected
      regions as markers for population-level studies.

PMID- 14961288
TI  - Milli-calpain from sea bass (Dicentrarchus labrax) white muscle: purification,
      characterization of its activity and activation in vitro.
AB  - A calcium-activated neutral cysteine protease was purified to homogeneity from
      Dicentrarchus labrax white muscle using three steps: hydrophobic interaction,
      anion exchange, and gel filtration chromatographies. The purified enzyme showed a
      native molecular weight of 124 kDa with an oligomeric structure (large subunit of
      80 kDa and small subunit of 24 kDa). It has been classified as a milli-calpain
      from its calcium sensitivity. Activity was maximal at pH 7.0, 24 degrees C in
      Tris buffer without NaCl as determined by means of a two-level experimental
      design and response surface methodology. Sea bass calpain is neither glycosylated
      nor phosphorylated and shared some common cleavage specificities and activation
      and autolysis mechanisms with other typical mammalian or invertebrates calpains.
      Calcium-induced activation and autolysis of calpain has been characterized
      together with the effect of the strontium cation acting as a calcium analog. On
      the basis of its in vitro properties, the contribution of the sea bass milli
      calpain to the process of postmortem deterioration of fish muscle is discussed,
      even though further information such as in vivo regulation or in vitro effects on
      myofibrils is required.

PMID- 14961289
TI  - Stable integration and functional expression of flounder growth hormone gene in
      transformed microalga, Chlorella ellipsoidea.
AB  - Chlorella is an attractive organism for complex recombinant protein production
      because of its eukaryotic characteristics and low cost for large-scale culture.
      Protoplasts of C. ellipsoidea were transformed with a vector containing the
      flounder growth hormone gene (fGH) under the control of the cauliflower mosaic
      virus 35S promoter, and the phleomycin resistance Sh ble gene under the control
      of the Chlamydomonas RBCS2 gene promoter. The presence of introduced DNA was
      first determined by PCR amplification of both the fGH and Sh ble genes from
      genomic DNA isolated from transformants and fGH protein expression was detected
      by immunoblot analysis. Over 400 microg of fGH protein expression per one liter
      culture containing 1 x 10(8) cells/ml was estimated by ELISA. Stable integration
      of introduced DNA was confirmed by Southern blot analysis of genomic DNA digested
      with restriction enzymes. The introduced DNA and fGH expression were detected
      after seven successive transfers in media devoid of phleomycin, but stably
      remained in the presence of the antibiotic. Flounder fry fed on the transformed
      Chlorella revealed a 25% growth increase after 30 days of feeding.

PMID- 14961290
TI  - Suppressive subtraction libraries to identify interferon-inducible genes in fish.
AB  - Previous attempts to identify genes in fish that respond to virus infection or
      interferon induction have not been particularly productive. Since these genes are
      very important in developing strategies to control disease outbreaks in
      aquaculture, we began a study of interferon-inducible genes in fish using
      suppressive subtraction hybridization to construct cDNA libraries enriched for
      interferon-inducible genes. Subtraction hybridization libraries were constructed
      with cDNA obtained from the kidney, spleen, and liver of Chinook salmon
      (Oncorhynchus tshawytscha) and staghorn sculpin (Hemilepidotus spinosus) before
      and after injection with poly IC, a potent interferon inducer. The "identified"
      genes in both cDNA libraries corresponded to previously identified genes of the
      fish complement system, the interferon-inducible proteins observed in mammalian
      cells, and the Vig-1 gene, identified in fish cells after infection with fish
      rhabdoviruses.

PMID- 14961291
TI  - Potential indicators of stress response identified by expressed sequence tag
      analysis of hemocytes and embryos from the American oyster, Crassostrea
      virginica.
AB  - A pilot program was initiated to identify genes from the American oyster,
      Crassostrea virginica, that are potentially involved in the stress response for
      use as bioindicators of exposure to environmental pollutants and to toxic and
      infectious agents. A PCR-based method was used to construct cDNA libraries from
      pooled embryos and the hemocytes of a single individual. A total of 998 randomly
      selected clones (expressed sequence tags, ESTs) were sequenced. Approximately 40%
      of the ESTs are novel sequences. Several potential biomarkers identified include
      an antimicrobial peptide, recognition molecules (lectin receptors), proteinases
      and proteinase inhibitors, and a novel metallothionein. Diversity analysis shows
      that 363 and 286 unique genes were identified from the hemocyte and embryo
      libraries, respectively, indicating that full-scale EST collection is a valuable
      approach for the discovery of new genes of potential significance in the
      molluscan stress response.

PMID- 14961293
TI  - Introduction: Aquaria fish models of human disease.

PMID- 14961292
TI  - Discrimination of the cell surface of the coccolithophorid Pleurochrysis
      haptonemofera from light scattering and fluorescence after fluorescein
      isothiocyanate-labeled lectin staining measured by flow cytometry.
AB  - We investigated the extent of calcification on the cell surface of the
      coccolithophorid Pleurochrysis haptonemofera using flow cytometry. Side
      scattering (SSC) by coccolith-bearing cells was higher than that by naked cells,
      suggesting the difference was due to scattering of the laser beam by the
      coccoliths. SSC of coccolith-bearing cells under acidic conditions corresponded
      well to the extracellular Ca content, although SSC could not be used to detect a
      delicate change in the coccolith thickness. The increase in SSC during the
      reproduction of coccoliths after decalcification was consistent with the increase
      in the number of coccoliths on the cell surface. The fluorescence after
      fluorescein-isothiocyanate-labeled lectin staining suggests that alpha- d
      mannose, alpha- d-glucose, d-galactose, d- N-acetylgalactosamine, or derivatives
      of them are included in the coccoliths. Measurement of SSC and fluorescence after
      fluorescein-isothiocyanate-labeled lectin staining enabled rapid and quantitative
      determination of the status on the cell surface and isolation of desirable cells
      for physiological studies by cell sorting.

PMID- 14961294
TI  - In appreciation of Klaus D. Kallman.

PMID- 14961295
TI  - How the Xiphophorus problem arrived in San Marcos, Texas.

PMID- 14961296
TI  - Three unique experimental fish stories: Poecilia (the Past), Xiphophorus (the
      Present), and Medaka (the Future).
AB  - These three stories exemplify the uniqueness of fish models in their abilities to
      answer important biological questions. The first one identifies the major UV
      induced damage (pyrimidine dimers) that is responsible for tumor induction.
      Thyroid cells from isogenic fish ( Poecilia formosa) were exposed to UV in vitro,
      then either exposed or not to photoreactivating light that monomerizes dimers,
      and the cells were injected into isogenic recipients. In the absence of
      photoreactivating light, the recipients developed tumors; in its presence, there
      were very few tumors. The second story describes our use of backcross hybrids of
      Xiphophorus as a model for melanoma induction by several UV and visible
      wavelengths. All the wavelengths were effective. (Squamous cell carcinomas in
      mice are induced preferentially by wavelengths <320 nm.) The data strongly
      suggest that light absorbed by the black pigment melanin damages DNA. The third
      story is designed to determine the mutagenic effects on sperm of the high atomic
      number, high-energy (HZE) nuclei present in cosmic rays by measuring mutations in
      progeny of exposed male medaka.

PMID- 14961297
TI  - Genetic analysis of susceptibility to spontaneous and UV-induced carcinogenesis
      in Xiphophorus hybrid fish.
AB  - Xiphophorus interspecies hybrids provide genetically controlled models of tumor
      formation. Spontaneous melanomas form in first-generation backcross (BC(1))
      hybrids produced from backcrossing F(1) hybrids derived from the platyfish X.
      maculatus Jp 163 A and the swordtail X. helleri to the X. helleri parental strain
      (the Gordon-Kosswig hybrid cross). Nodular melanomas originate in the dorsal fin
      from cells constituting the spotted dorsal (Sd) pigment pattern. A parallel
      genetic cross, with X. maculatus Jp 163 B, exhibits the spotted side (Sp) pigment
      pattern instead of Sd, and produces BC(1) hybrids exhibiting a much lower
      frequency of spontaneous melanoma formation. These hybrids are susceptible to
      melanoma development if irradiated with UV light as fry. Other hybrids involving
      these two strains of X. maculatus and different swordtail and platyfish backcross
      parents also have been investigated as potential tumor models, and show differing
      susceptibilities to UV-induced and spontaneous melanomas. Genotyping of
      individual BC(1) hybrids from several Xiphophorus crosses has implicated a locus,
      CDKN2X (a Xiphophorus homologue of the mammalian CDKN2 gene family, residing on
      Xiphophorus linkage group V), in enhancing pigmentation and the susceptibility to
      spontaneous and UV-induced melanoma formation in BC(1) hybrids from some crosses,
      but not others. Homozygosity for X. helleri and X. couchianus CDKN2X alleles in
      BC(1) hybrids can predispose individuals to melanoma, but this susceptibility is
      modified in other crosses depending both on the contributing sex-linked pigment
      pattern locus from X. maculatus (Sd or Sp), and the genetic constitution of the
      backcross parent. Xiphophorus BC(1) hybrids constitute unique genetic models
      offering the potential to analyze the contributions of specific genes to
      spontaneous and induced tumor formation in different, but comparable genetic
      backgrounds.

PMID- 14961298
TI  - Genetic analysis of neoplasia induced by N-nitroso-N-methylurea in Xiphophorus
      hybrid fish.
AB  - Interspecific crosses within the genus Xiphophorus have historically been used to
      study the genetic aspects of melanoma formation. Melanomas typically occur as a
      result of deregulation of polymorphic, naturally occurring macromelanophore
      pigment patterns. Hybrid crosses also have been used to study the inducibility of
      melanoma by physical sources (such as UV light) and chemicals (such as N-methyl-N
      nitrosourea, MNU). We previously defined a genomic region that is implicated in
      fish melanomagenesis and identified a candidate tumor suppressor gene (CDKN2X)
      within this genomic area. Highly significant associations between BC(1)-hybrid
      CDKN2X genotypes and UV-induced melanoma formation exist in a backcross produced
      from 2 inbred parental lines. However, when BC(1) hybrids are exposed to MNU as
      the tumor induction agent, a significant association between inheritance of
      CDKN2X alleles and tumor development is not observed. These data suggest there is
      mechanistic and genetic heterogeneity in melanomas derived from different
      etiologies within BC(1) hybrid fish.

PMID- 14961299
TI  - Retinoblastoma gene mutations in chemically induced liver tumor samples of
      Japanese medaka (Oryzias latipes).
AB  - Alterations in the retinoblastoma ( Rb) gene have been correlated with a large
      number and wide variety of human tumors, including hepatocellular carcinoma. We
      have previously characterized a medaka homologue of the human Rb complementary
      DNA that is conserved in regions of functional importance. Structural alterations
      in the entire coding region (exons 1 to 27) of the Rb gene in methylene-chloride
      induced medaka liver tumors were investigated using polymerase chain reaction and
      single strand conformation polymorphism analysis. Four of 5 liver tumors were
      found to have Rb alterations. Sequencing revealed 7 point mutations in exons 18
      and 23, resulting in 5 amino acid substitutions, and a deletion within exon 19.
      Our results suggest that the molecular etiology of the medaka hepatocellular
      carcinoma models appear similar to that reported in humans. As such, the medaka
      appears to be a valid model for the study of Rb-implicated tumorigenesis.

PMID- 14961300
TI  - Relative base excision repair in Xiphophorus fish tissue extracts.
AB  - To begin characterizing DNA repair capability among Xiphophorus species, we
      adapted oligonucleotide-based DNA repair assays to extracts of fish tissues.
      Here, we report the initial results of relative base excision repair (BER)
      capability among 3 inbred Xiphophorus fish lines representing 2 species (X.
      maculatus and X. couchianus), and interspecies hybrid F(1) animals produced by
      crossing them. Overall, data from uracil- N-glycosylase (UNG)-initiated BER assay
      (UNG-BER) indicate that brain tissue extracts generally possess higher BER
      activity than do gill and liver extracts. UNG-BER activities in gill and liver
      extracts were similar. The BER activity in the tissues of F(1) interspecies
      hybrids followed the activity pattern of the X. couchianus parent in gill and
      liver extracts, was similar to the X. maculatus parent in brain extracts, but
      exhibited a reduced repair capacity in gill tissue extracts compared with either
      parent. We discuss the use of oligonucleotide-based DNA repair assays to
      elucidate the role that inheritance of DNA repair potential may play in
      susceptibility to disease and tumorigenesis in the intact organism.

PMID- 14961301
TI  - Resolution of UV-induced DNA damage in Xiphophorus fishes.
AB  - The genus Xiphophorus is an important model for investigating the etiology and
      genetics of sunlight-induced melanoma as well as other cancers. We investigated
      the role DNA damage plays in tumorigenesis in Xiphophorus using a variety of
      immunological techniques to examine the induction, distribution, and repair of
      the major photoproducts in DNA after exposure to solar (ultraviolet-B) radiation.
      We found that cyclobutane pyrimidine dimers (CPDs) were induced at 5- to 10-fold
      greater frequency than the (6-4) photoproduct ((6-4)PD) in Xiphophorus signum,
      and the efficiency of photoproduct formation was tissue-dependent, with the
      scales providing considerable photoprotection against both types of damage. Both
      of these lesions are efficiently repaired in the presence of visible light by
      photoenzymatic repair with CPDs repaired at about twice the rate of (6-4)PDs.
      Photoenzymatic repair of cyclobutane dimers is inducible by prior exposure to low
      levels of visible light and can be extremely rapid, with most of the lesions
      removed within 30 minutes. In the absence of light, dimers are removed by
      nucleotide excision repair with somewhat greater efficiency for the (6-4)PD
      compared with the CPD in most species. The relative efficiencies of nucleotide
      excision repair and photoenzymatic repair are tissue-specific and species
      specific. The diverse photochemical and photobiological responses observed in
      Xiphophorus fishes suggest that heritable traits governing the induction and
      repair of DNA damage may be involved in the susceptibility of Xiphophorus hybrids
      to melanomagenesis.

PMID- 14961302
TI  - Genomic plasticity and melanoma formation in the fish Xiphophorus.
AB  - Melanoma formation in certain interspecific hybrids of the genus Xiphophorus
      (Teleostei: Poeciliidae) is associated with the overexpression of the Xmrk
      receptor tyrosine kinase oncogene. The Xmrk oncogene arose by duplication of the
      pre-existing Xmrk protooncogene in a highly unstable subtelomeric region of the X
      and Y sex chromosomes undergoing frequent rearrangements including duplications,
      deletions, amplifications, and transpositions. Some of these rearrangements are
      likely to be responsible for the overexpression of the Xmrk oncogene in melanoma.
      The oncogene itself is very unstable in Xiphophorus and is frequently removed by
      deletion or disrupted by transposable elements. The Xmrk oncogene region displays
      a high concentration of retroelements not observed in the corresponding Xmrk
      protooncogene region. Particularly, a retrovirus long terminal repeat-like
      sequence was amplified in the proximity of the Xmrk oncogene. Additional genes,
      some of them also duplicated copies, were detected in this region and might be
      involved in modulating the melanoma's phenotype.

PMID- 14961303
TI  - Reporter gene expression in fish following cutaneous infection with pantropic
      retroviral vectors.
AB  - A central issue in gene delivery systems is choosing promoters that will direct
      defined and sustainable levels of gene expression. Pantropic retroviral vectors
      provide a means to insert genes into either somatic or germline cells. In this
      study, we focused on somatic cell infection by evaluating the activity of 3
      promoters inserted by vectors into fish cell lines and fish skin using pantropic
      retroviruses. In bluegill and zebrafish cell lines, the highest levels of
      luciferase expression were observed from the 5' murine leukemia virus long
      terminal repeat of the retroviral vector. The Rous sarcoma virus long terminal
      repeat and cytomegalovirus early promoter, as internal promoters, generated lower
      levels of luciferase. Luciferase reporter vectors infected zebrafish skin, as
      measured by the presence of viral DNA, and expressed luciferase. We infected
      developing walleye dermal sarcomas with retroviral vectors to provide an
      environment with enhanced cell proliferation, a condition necessary for
      integration of the provirus into the host genome. We demonstrated a 4-fold to 7
      fold increase in luciferase gene expression in tumor tissue over infections in
      normal walleye skin.

PMID- 14961304
TI  - Genetic relationship of tumor-associated piscine retroviruses.

PMID- 14961305
TI  - A proposed classification scheme for Xiphophorus melanomas based on
      histopathologic analyses.
AB  - We studied the histopathologic characteristics of melanomas induced in the
      Xiphophorus model. This fish model has been used for several decades to study the
      molecular and genetic mechanisms underlying its susceptibility to melanoma
      induction. Numerous distinct interspecific hybrid crosses currently are being
      used in research on carcinogenesis. We previously reported that tumors were
      induced in such hybrid crosses after treatment with N-methyl-N-nitrosourea or UV
      radiation. In this report, we describe the histopathologic features of
      Xiphophorus melanomas and propose a new classification system. We suggest that
      melanomas in these fishes can be classified as follows: melanocytic melanomas;
      melanophorous-macromelanophorous polymorphic melanomas; spindle cell type
      melanomas; epithelioid cell melanomas; and amelanotic melanomas. The new
      classification of Xiphophorus melanomas should allow correlations between
      histopathologic characteristics and carcinogen treatment, and between
      histopathologic characteristics and the genetic background of the hybrid fish.

PMID- 14961306
TI  - Progression of infection and tumor development in damselfish.
AB  - The bicolor damselfish (Stegastes partitus) is a tropical marine teleost
      naturally affected by multiple neurofibromas and chromatophoromas on South
      Florida reefs. Damselfish neurofibromatosis is a transmissible disease caused by
      a subcellular agent. Development of tumors is associated with the appearance of a
      series of extrachromosomal DNAs ranging in size from 1.2 to 7 kb that appear to
      be the genome of a small virus-like agent which we termed the damselfish virus
      like agent (DVLA). This DNA was found at high copy number in most spontaneous and
      experimentally induced tumors. An essentially identical pattern of DNA, but with
      lower copy numbers, was observed in non-tumor-bearing tissue from diseased fish.
      Copy numbers of DVLA DNA in tumors and nontumorous tissues increased as the
      disease progressed from early to late stages. In healthy fish in which DVLA DNA
      was detected, the quantities were much lower than those in diseased fish. Healthy
      fish from populations with a high prevalence of disease exhibited more infected
      tissues than fish from populations with low levels.

PMID- 14961307
TI  - Lesser known aquarium fish tumor models.
AB  - The repeated use of particular species for experimental oncology in fish
      increases their future value by accumulating background information for these
      models and justifies the establishment of genetic stock centers. However, the
      wide diversity that exists within the class Osteichthyes and Chondrichthyes
      suggests that the ideal surrogate models for studying some types of neoplasms
      might be found among lesser known species. To help assess cultured fish as
      surrogates for some other types of human neoplasia, we examined cases in the
      archives of the Registry of Tumors in Lower Animals and reviewed reports in the
      literature. Spontaneous and induced neoplasms originating from a spectrum of cell
      types were seen in more than 215 fish species commonly raised in aquaria or
      cultured for study among 69 families. Prominent families include the Poeciliidae
      (livebearers), Cyprinidae (carps and minnows), Cichlidae (cichlids),
      Cyprinodontidae (killifish), Characidae (tetras), Adrianichthyidae (medakas),
      Aplocheilidae (rivulins), and Salmonidae (salmon and trout). The following are
      examples of potential fish tumor models that have received less consideration
      than some others: papilloma and carcinoma of the urinary bladder in oscar
      (Astronotus ocellatus); osteogenic neoplasms, peripheral nerve sheath tumors, and
      ependymoblastoma in coho salmon fingerlings (Oncorhynchus kisutch); and
      nephroblastoma resembling Wilms' tumor in Japanese eels (Anguilla japonica).

PMID- 14961308
TI  - Use of the Japanese pufferfish (Fugu rubripes) in comparative genomics.
AB  - With the draft sequence of the human genome available and an increasing number of
      organisms being sequenced, attention is becoming focused on sequence
      interpretation and functional analysis. Comparative genomics will play an
      important role in evaluating these data. At the molecular level, roles for
      uncharacterized proteins can be hypothesized by identifying conserved protein
      domains and putative noncoding regulatory elements can be defined from direct
      sequence comparisons of evolutionarily distant organisms. At a higher level,
      questions, such as the importance of gene order positioning, conservation of
      linkage, and genome evolution, can begin to be answered by collecting map data
      from different organisms. This minireview, centering on Fugu regions sharing
      synteny with human chromosomes 11p, 20q, and 6p21.3, details some of the ways in
      which the Japanese pufferfish can contribute to the study of comparative genomics
      and evaluation of sequence data from the genome programs.

PMID- 14961309
TI  - Comparative genomics of medaka: the major histocompatibility complex (MHC).
AB  - The major histocompatibility complex (MHC) is one of the best characterized
      regions of the vertebrate genome. The human MHC has three subregions, classes I,
      II, and III. The MHC of chicken and Xenopus contain all three subregions. In
      contrast, in all teleost species so far analyzed, the class I and II genes are
      not linked to each other, suggesting that there was extensive genomic
      reorganization of the MHC region during an early stage of vertebrate evolution.
      To elucidate the details of this reorganization, we carried out genetic and
      physical analyses of the medaka MHC genes. We isolated the medaka counterparts of
      human MHC genes, class I A, class II B, LMP2, LMP7, TAP2, complement Bf and C4,
      and subjected them to linkage analysis. Except for the linkage of class IA, LMP2,
      LMP7, and TAP2 on linkage group (LG)11, all other genes were assigned to separate
      linkage groups. Thus, the class IA gene and the genes involved in class I antigen
      presentation seem to form the evolutionary stable core of the MHC. A physical
      analysis of medaka MHC class I region is in progress.

PMID- 14961310
TI  - Application of fluorescence in situ hybridization (FISH) to fish genetics and
      genome mapping.
AB  - The various applications of the technique of fluorescence in situ hybridization
      (FISH) to fish genetics will be reviewed for fishes being used as model organisms
      to study human disease, including those species for which major genome projects
      have been initiated. "FISH on fish" has been used to map highly repetitive
      sequences including centromere-specific sequences and sex-specific sequences,
      moderately repetitive sequences such as rRNAs and histones, and single-copy
      sequences. Paint probes specific for whole genomes, whole chromosomes, and
      chromosome subregions have been prepared for several species. The potential
      future applications of FISH to fish genetics and genome mapping will be
      discussed.

PMID- 14961311
TI  - Xiphophorus genetic linkage map: beginnings of comparative gene mapping in
      fishes.
AB  - The explosive expansion of gene maps of mouse and man has provided strong support
      for hypotheses first advanced from comparing fish and mammalian genomes that the
      vertebrate genome was derived from multiple ancestral tetraploidizations with
      subsequent preferential translocations among paralogous chromosomes. At least two
      genome duplication events have become widely accepted in lineages leading to
      vertebrates, and a third has been proposed either before, or after, divergence of
      fishes and tetrapods. Cytogenetic and comparative gene mapping studies suggest
      that teleost gene maps have diverged more slowly from gene arrangements in the
      vertebrate ancestor than have those of mammals. The recent assembly of extensive
      maps of >100 genes in three fish species, medaka (Beloniformes), Xiphophorus
      swordtails and platyfishes (Cyprinodontiformes), and zebrafish (Cypriniformes)
      and the development of less extensive maps in several other fish orders provides
      the first salient opportunity to assess homology of most or all chromosomes among
      fishes.

PMID- 14961312
TI  - The medaka as a model for studying germ-cell mutagenesis and genomic instability.
AB  - To study germ-cell mutagenesis from the viewpoint of biodiversity, we developed a
      nonmammalian specific-locus test system using the Japanese medaka, Oryzias
      latipes. The genetic end points available are dominant lethal mutations, total
      specific-locus mutations, and viable specific-locus mutations. We examined
      1,091,824 F(1) embryos that correspond to 3,135,999 genetic loci using gamma rays
      and ethylnitrosourea as mutagens. The results indicated the feasibility of using
      the medaka test system to detect genotoxic substances in the aquatic environment.
      The data also indicated the presence of in vivo safeguards against germ-cell
      mutagenesis. We present a brief summary of our medaka specific-locus test system
      raising perspectives on its value.

PMID- 14961313
TI  - Transformation-associated recombination (TAR) cloning of tumor-inducing Xmrk2
      gene from Xiphophorus maculatus.
AB  - We modified the TAR methodology of YAC clone construction for application to fish
      genomic DNA isolated from Xiphophorus maculatus. YAC libraries were developed
      using the XIR1 repeat sequence as the recombinational hook. Construction of these
      libraries demonstrates that Xiphophorus DNA sequences can function as hooks in
      the yeast recombination system and that X. maculatus genomic DNA contains
      sequences that provide origin of replication function in yeast. By screening a
      subset of Xiphophorus YAC clones, we isolated a clone harboring the Xmrk2 locus
      that is associated with spontaneous and induced melanomagenesis. Modifications of
      the TAR technique allowed the targeted cloning of specific genes from genomic
      regions ranging in size from cDNAs to several hundred kilobases. Specific genomic
      regions can be isolated in a directional manner from fixed map locations to
      saturate these areas with physical markers. We discuss the applications of these
      and other yeast recombinational processes to fish genetics.

PMID- 14961314
TI  - Production of transgenic live-bearing fish and crustaceans with replication
      defective pantropic retroviral vectors.
AB  - Transgenic fish have been routinely produced by microinjecting or electroporating
      foreign DNA into one-cell stage embryos or unfertilized eggs. While both
      techniques are effective in producing transgenic fish species from which
      unfertilized or newly fertilized eggs can be easily obtained, these techniques
      are not applicable to live-bearing fish and many crustacean species where
      unfertilized or newly fertilized eggs are not readily available. In this paper,
      we describe a new method of introducing foreign DNA into the live-bearing fish,
      Poeciliposis lucida, and crayfish, Procambarus clarkii, by directly transforming
      the immature ovary or testis of these animals with replication-defective
      pantropic retroviral vectors carrying a reporter gene (neo(R)). A significant
      fraction of the progeny derived from these treated animals contains the neo(R)
      reporter gene, determined by a PCR-based assay. The PCR-positive individuals were
      crossed with nontransgenic individuals, and about 50% of the resulting progeny
      carried the transgene, suggesting that the F(1) animals are germline transgenic.
      Integration of the transgenes was confirmed by detecting the junction fragments
      of the genomic DNA associated with transgene constructs. The expression of
      reporter genes was detected by reverse transcription (RT) PCR assay. These
      results showed that foreign genes could be reproducibly transferred into live
      bearing fish and crustaceans by directly transforming the immature gonads with
      replication-defective pantropic retroviral vectors.

PMID- 14961315
TI  - Bacteriophage lambda and plasmid pUR288 transgenic fish models for detecting in
      vivo mutations.
AB  - We adapted transgenic rodent mutation assays based on fish carrying bacteriophage
      lambda and plasmid pUR288 vectors to address the needs for improved methods to
      assess health risks from exposure to environmental mutagens and also to establish
      new animal models to study in vivo mutagenesis. The approach entails separating
      the vectors from fish genomic DNA and then shuttling them into specialized
      strains of E. coli bacteria to analyze spontaneous and induced mutations in
      either lacI and cII or lacZ mutational targets. Fish exhibited low frequencies of
      spontaneous mutants comparable to the sensitivity of transgenic rodent models.
      Mutations detected after treating fish with chemical mutagens showed
      concentration-dependent, tissue-specific, and time-dependent relationships.
      Spontaneous and induced mutational spectra also were consistent with the
      specificity of known mutagens, further supporting the utility of transgenic fish
      for studies of in vivo mutagenesis.

PMID- 14961316
TI  - Cell cultures and retroviral particles from a tumor of a moray eel.
AB  - Until recently, fish cell culture primarily has been useful only in the
      propagation and study of epidemic viruses significant to the fishing industry.
      Such fish cell lines derived were developed by appropriating classical techniques
      of mammalian cell culture, with serum as the major growth supplement. Using an
      approach in which culture medium is formulated in a cell-type-specific manner
      with minimal serum and a variety of synergistic supplements, several fish cell
      lines have been derived that may serve multiple uses. We established cell lines
      from a potentially tumorous skin lesion of a green moray eel (Gymnothorax
      funebris) and control tissues, and identified putative retroviral particles in
      the medium from the tumor cells that are not present in medium from cultures of
      normal cells from the same eel. The relationship between the virus and the cause
      of the tumor is not clear, but the genomic structure of this virus should provide
      useful information in understanding the evolution of retroviruses in general.

PMID- 14961317
TI  - Utility of natural populations for microarray analyses: isolation of genes
      necessary for functional genomic studies.
AB  - How much variation is there in gene expression? How is this variation partitioned
      within and among populations? How much variation is biologically important? That
      is, how much of this variation affects longevity, reproductive fitness, or
      probability of survival? Microarray analyses can be used to accurately quantify
      the expression of most, if not all, genes expressed in a tissue and thus address
      the first question. The latter questions can be investigated by examining the
      patterns of variation within and among natural populations of Fundulus. These
      populations are large and affected by historical, demographic, and selective
      constraints, providing a framework for the partition of variation in gene
      expression within and among populations. Additionally, the well established,
      phylogenetic relationship among Fundulus species can be used to discern adaptive
      change. A phylogenetic perspective reveals changes that are produced by natural
      selection and therefore indicates whether this variation affects longevity,
      reproductive fitness, or probability of survival, i.e., whether the variation is
      biologically important. However, a Fundulus microarray requires DNAs encoding
      specific Fundulus genes. This paper provides information on the production,
      isolation, and characterization of 4440 Fundulus cDNAs used in microarrays. Our
      approach was to pick random colonies from a normalized cDNA library and then PCR
      amplify and sequence these genes in a 96-well format. Periodically, the isolated
      and sequenced cDNAs were subtracted from the normalized library. Normalization
      reduced the number of redundant genes from 33% to 11%, increasing the
      effectiveness of this screening process. From 4440 sequenced cDNAs, 49% (2173)
      had a match in GenBank using BlastX searches. Of these, 53% were nonredundant,
      yielding 1149 identified genes. These data suggest that cDNAs necessary for
      microarray analyses can be produced effectively from most organisms.

PMID- 14961318
TI  - Cryopreservation in aquarium fishes.
AB  - Few studies have addressed sperm cryopreservation in aquarium fishes (body sizes
      of 10 cm or less). There are several challenges inherent in developing
      cryopreservation procedures for these fishes. First, their small body size and
      sperm volume limit experimental replication and the numbers of treatments
      possible without pooling of samples. This hinders research, especially if many
      experimental variables are evaluated. The small sample volume necessitates
      identification of optimal sperm-to-egg ratios to maximize fertilization potential
      and places greater emphasis on increasing and maintaining sperm viability after
      thawing. Other technical problems include the use of 0.25-ml French straws, which
      increase difficulties in sample handling (automated straw fillers are more common
      for the 0.5-ml straw) and labeling. Sperm cryopreservation of live-bearing fishes
      (with internal fertilization) is essentially unexplored. The sperm of these
      fishes is sufficiently different in structure (e.g., head shape) and physiology
      (e.g., energy metabolism) from the sperm of other fishes that the need to develop
      specialized techniques is almost assured. The requirement for artificial
      insemination also introduces a new variable complicating the collection of data
      (e.g., assessing fertilization is not straightforward with internally held eggs).
      Cryopreservation in aquarium fishes will assist the development (e.g., through
      selective breeding), protection (e.g., through germplasm repositories), and
      distribution (e.g., through shipment of frozen sperm) of research lines and
      offers benefits for restoration of endangered species.

PMID- 14961319
TI  - Dioxin toxicology and the aryl hydrocarbon receptor: insights from fish and other
      non-traditional models.
AB  - Fish are established models in biology. Recent findings suggest that fish and
      other nontraditional species also may serve as valuable model systems for
      understanding receptor-dependent signaling pathways and their interactions with
      environmental chemicals. Because they are highly sensitive to chlorinated dioxins
      and related halogenated aromatic hydrocarbons, fish are being used to elucidate
      the role of chemical signaling pathways in the developmental and molecular
      toxicology of dioxin-like compounds. Much of this work is focused on the aryl
      hydrocarbon receptor (AHR), a ligand-activated, bHLH-PAS transcription factor
      through which dioxins cause altered gene expression and toxicity. In contrast to
      mammals, which appear to express a single dioxin-binding AHR, many fish species
      possess at least two AHR genes. Studies of these two fish AHRs may help to reveal
      the multiple functions of the single mammalian "AHR," its physiological ligand,
      and the molecular mechanisms involved in differential sensitivity to dioxin-like
      compounds. In addition, fish have great potential as models for understanding the
      in vivo functions and interactions of bHLH-PAS proteins, the evolutionary history
      of their diversification in vertebrates, and their role in human physiology and
      disease.

PMID- 14961320
TI  - Four resource centers for fishes: specifies, stocks, and services.
AB  - A conference on "Aquaria Fish Models of Human Disease" was held September 20-23,
      2000, at Southwest Texas State University, San Marcos, Texas, USA. The meeting
      was sponsored by the National Cancer Institute (National Institutes of Health),
      the Roy and Joan Mitte Foundation, and Southwest Texas State University, home of
      the Xiphophorus Genetic Stock Center. In conjunction with the meeting, the
      conference organizers asked several participants to describe those components of
      their research programs that provide services and information to other
      researchers. This article summarizes their responses.

PMID- 14961321
TI  - Aquaria fish models of human disease: reports and recommendations from the
      working groups.
AB  - On September 21-24, 2000, the National Cancer Institute, Southwest Texas State
      University, and the Roy and Joan Mitte Foundation sponsored an international
      conference entitled "Aquaria Fish Models of Human Disease" at Southwest Texas
      State University (SWT), San Marcos, Texas, USA. Over 100 scientists, representing
      various fish model systems, participated in four roundtable working groups. We
      considered the first step in promoting the exciting research with fish models was
      to unify the efforts within this scientific community towards accomplishing
      specific goals. With this objective in mind, the following four working groups
      were convened: (1) fish cancer models: sustenance and enhancement; (2) fish
      genomics and transgenics: resources and technology; (3) fish pathology: standards
      for tumor pathology classification; and, (4) resources underpinning aquaria fish
      research. Each working group was charged with preparing a report of their
      discussions with recommendations on how researchers and funding agencies might
      best direct and strengthen research support to ensure a healthy future for such
      work. Included are the final reports from these working groups, together with a
      brief summary of the discussions held during the sessions and the consensus
      recommendations from each group.

PMID- 14961322
TI  - Molecular discrimination of garfish Hyporhamphus (Beloniformes) larvae in
      southern Australian waters.
AB  - A multiplex polymerase chain reaction (PCR) assay developed for discrimination
      between garfish larvae (family Hemiramphidae, order Beloniformes) found in
      southern Australian waters was based on species-specific amplification of part of
      the mitochondrial control region. The species were easily discerned by the number
      and distinct sizes of PCR products (Hyporhamphus melanochir, 443 bp; H.
      regularis, 462 and 264 bp). Although based on a single gene, the method will
      correctly identify the species of individuals in at least 96% of tests for H.
      melanochir and 94% of tests for H. regularis.

PMID- 14961323
TI  - Presence of a nonhydrolyzable biopolymer in the cell wall of vegetative cells and
      astaxanthin-rich cysts of Haematococcus pluvialis (Chlorophyceae).
AB  - The green alga Haematococcus pluvialis accumulates massive amounts of the red
      pigment astaxanthin in response to stimuli inducing it to form cysts. During the
      encystment process the cell wall undergoes a clear hardening and thickening. In
      this work, a cell wall fraction withstanding successive acid and basic hydrolysis
      was isolated and proves to be algaenan by Fourier transform infrared
      spectroscopy. This compound is equally abundant in nonmotile vegetative cells and
      astaxanthin-rich cysts. This finding indicates that the synthesis of algaenan
      does not require the activation of the machinery for the massive production of
      secondary carotenoids. We conclude that algaenan cannot cause the changes
      occurring in the cell wall during the encystment process without the involvement
      of other cell wall components.

PMID- 14961324
TI  - Generating transparent zebrafish: a refined method to improve detection of gene
      expression during embryonic development.
AB  - In zebrafish (Danio rerio) pigmentation is initiated during embryogenesis and
      begins in the retinal epithelium and in the melanophores. The pigment cells
      develop rapidly, and within hours they constitute a prominent feature of the
      embryo. In order to improve signal detection by whole mount in situ
      hybridization, confocal microscopy, or expression of GFP, embryos may be treated
      with 1-phenyl 2-thiourea (PTU) during embryogenesis. PTU inhibits melanogenesis
      by blocking all tyrosinase-dependent steps in the melanin pathway but can be
      toxic at high concentrations. The embryos remain transparent as long as the PTU
      treatment is continued. However, PTU treatment must be initiated before the
      initial pigmentation because it does not remove already formed pigment. Here we
      provide a protocol for generating transparent zebrafish while avoiding the toxic
      and teratogenic effects of PTU treatment.

PMID- 14961325
TI  - Evaluation of marine bacterial lysogens for development of a marine prophage
      induction assay.
AB  - The demonstrated relationship between carcinogenicity of a chemical compound in
      mammals and its tendency to cause prophage induction in bacteria provides a
      method for biologically based carcinogen screening. Because of the need for this
      type of screening and the abundance of lysogens in the marine environment, 14
      isolates were evaluated for the degree of prophage induction in exponentially
      growing cultures in the presence of a known mutagen (0.5 microg/ml mitomycin C).
      Assays were performed both in liquid culture and in microtiter plates. Virus-like
      particles were enumerated by epifluorescence microscopy after staining with SYBR
      Gold. Two isolates designated P94-4B3 (identified as Halomonas aquamarina) and
      P94-4S3 (identified as Pseudomonas aeruginosa) were further evaluated for
      potential use. Because of the rapid growth, larger size of its virus-like
      particles, and linear response to increasing dose of mitomycin C, the P.
      aeruginosa st. P94-4S3 was determined a better candidate for the marine prophage
      induction assay (MPIA). The Pseudomonas isolate was then used in several
      experiments for the development and optimization of the MPIA procedure. Initial
      screenings of the MPIA were also performed with selected environmental
      pollutants.

PMID- 14961326
TI  - Transgenic medaka overexpressing a melanin-concentrating hormone exhibit
      lightened body color but no remarkable abnormality.
AB  - Melanin-concentrating hormone (MCH) is a cyclic heptadecapeptide that
      concentrates melanin granules in the melanophores and lightens the body color of
      a fish. To investigate the utility of MCH as a reporter gene, a transgenic medaka
      strain overexpressing the MCH gene was established and its phenotypic features
      were examined. The salmon MCH gene driven by cytomegalovirus promoter was
      injected into 100 fertilized eggs of the HNI-1 medaka strain, which exhibits
      black body color. One F(0) female transmitted the transgene and a lightened body
      color phenotype to the F(1) generation. A homozygous transgenic strain was
      established by crossing F(2) fish homozygous for the transgene. Expression of the
      transgene was detected in several organs by Northern blotting. The melanin
      granules of transgenics were highly shrunk. Bioassay using scales confirmed the
      secretion of MCH into blood, and the MCH concentration was estimated between 0.5
      and 5 microM. Development, growth, feeding behavior, and reproduction of
      transgenics did not differ significantly among transgenic and nontransgenic
      siblings. The result whereby enhanced MCH expression induced a change in body
      color, but no remarkable abnormality, suggests the usefulness of MCH as a novel
      reporter gene with unique features.

PMID- 14961327
TI  - Development of in vivo sponge cultures: particle feeding by the tropical sponge
      Pseudosuberites aff. andrewsi.
AB  - The rate of food particle uptake of the tropical sponge Pseudosuberites aff.
      andrewsi was studied in relation to particle concentrations and particle size. A
      range of different concentrations of either the marine microalga Dunaliella
      tertiolecta (approximately 5-8 microm) or the marine cyanobacterium Synechococcus
      sp. (approximately 1 microm) was supplied to the sponges. D. tertiolecta had a
      pronounced effect on the filtration activity of the sponges: at concentrations
      higher than approximately 4 x 10(5) cells/cm(3), the filtration rates dropped
      dramatically. Such a clear effect was not found for Synechococcus sp. The results
      further showed that the maximal amount of food (when expressed in organic carbon)
      that can be taken up per cubic centimeter of sponge volume per unit of time
      should in principle be sufficient to enable growth (irrespective of the food
      particle type). At the maximal food particle concentration that did not affect
      the filtration rates, the uptake of organic carbon is already highly in excess of
      the amount of organic carbon that the sponges need to cope with their respiratory
      demand. Based on these findings, a series of growth experiments was carried out
      in which the sponges were subjected to a constant concentration of different
      types of food particles (Synechococcus sp. and the microalgae Chlorella
      sorokiniana and Nannochloropsis sp). Although initial growth was sometimes
      observed, continuous growth at a constant rate could not be obtained. It is
      concluded that qualitative aspects of feeding rather than quantitative aspects
      are the key to successful in vivo sponge culture.

PMID- 14961328
TI  - Elucidation of the molecular basis of a null allele in a rainbow trout
      microsatellite.
AB  - The use of microsatellites for studies of population structure, as markers in
      genome mapping, and for parentage control has become increasingly popular in
      recent years. However, the presence of null alleles can lead to confounding
      results when using microsatellites. In the Omy3DIAS microsatellite, the presence
      of a null allele was discovered by analysis of family material. The null allele
      was sequenced after amplification with new primers located farther away from the
      repeat sequence. The null allele was shown to be caused by a deletion of a 4-bp
      sequence, which was part of a repetitive sequence within one of the primer
      recognition sites. As this phenomenon has been seen in other cases of null
      alleles, this observation leads to the recommendation to avoid repetitive
      sequences of any kind within primer sequences. Allele-specific amplification of
      the null allele revealed the presence of a single variant of this allele.

PMID- 14961329
TI  - Development of vitellogenin-ELISA, an in vivo bioassay, and identification of two
      vitellogenesis-inhibiting hormones of the tiger shrimp Penaeus monodon.
AB  - A sandwich enzyme-linked immunosorbent assay (ELISA) for the quantification of
      vitellogenin in the hemolymph of Penaeus monodon is reported. Lipovitellin from
      the mature ovary was purified using hydroxylapatite column chromatography and
      used as the standard protein, which was serially diluted from 3336 to 6.51 microg
      and gave a linear plot. Sensitivity results showed ELISA was insensitive to
      samples that did not contain vitellogenin or lipovitellin. Specificity results
      showed the degree of the discrimination of the assay between positive samples
      (having vitellogenin or lipovitellin) and negative samples (devoid of
      vitellogenin or lipovitellin). Reproducibility studies showed that the intraassay
      coefficient of variation was 5.1% (n = 11) and the interassay coefficient of
      variation was 5.15% (n = 13). Separation of X-organ sinus gland peptides using a
      reversed phase column gave a total of 37 fractions. Two fractions were found to
      reduce the hemolymph vitellogenin concentration in a time-dependent manner and
      could be identified as vitellogenesis-inhibiting hormones I and II.

PMID- 14961330
TI  - Application of microsatellite markers to population genetics studies of Japanese
      flounder Paralichthys olivaceus.
AB  - We examined population genetic structure by means of microsatellite analysis
      among 7 Japanese flounder (Paralichthys olivaceus) populations collected from
      coastal sea areas around Japan. As was expected, all of the 11 microsatellite
      loci examined were variable in all populations (number of alleles per locus, 15.2
      18.2; average of expected heterozygosity, 0.74-0.78). Eleven population pairs in
      21 possible pairwise comparisons showed significant genetic heterogeneity
      associated with allele frequency distributions or fixation index (F(ST)).
      Modified Cavalli-Sforza chord distance (D(A)) and Nei's standard genetic distance
      (D(ST)) ranged from 0.051 to 0.090, and from 0.000 to 0.025, respectively. There
      was evidence that the populations assessed in this study were not drawn from a
      single panmictic population; however, it appears that Japanese flounder
      populations around Japan are not well-structured, as an estimate of the fixation
      index value among the 7 localities was very low (F(ST) = 0.0025).

PMID- 14961331
TI  - Channel catfish follicle-stimulating hormone and luteinizing hormone:
      complementary DNA cloning and expression during ovulation.
AB  - Gonadotropins are important regulators of reproduction. To develop molecular
      resources for production of recombinant gonadotropins, we have cloned and
      sequenced complementary DNA encoding the channel catfish (Ictalurus punctatus)
      follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which encode 132
      and 140 amino acid proteins, respectively. The deduced amino acid sequences of
      the catfish FSH and LH are highly conserved with those cloned from other
      teleosts. Both the FSH and the LH were highly induced during ovulation after
      injection of carp pituitary extract. Taken together with our previous findings of
      enhanced expression of growth hormone and other pituitary hormones, this research
      suggests that a hormonal cocktail may be needed for more efficient manipulation
      of catfish reproduction. The availability of the catfish FSH and LH cDNAs
      provides the opportunity for production of immunologically or biologically active
      recombinant gonadotropins for the study of catfish reproductive physiology and
      the manipulation of artificial spawning for aquaculture.

PMID- 14961332
TI  - Detection and phylogenetic analysis of novel crenarchaeote and euryarchaeote 16S
      ribosomal RNA gene sequences from a Great Barrier Reef sponge.
AB  - The presence of Archaea in the Great Barrier Reef marine sponge Rhopaloeides
      odorabile was investigated by 16S ribosomal RNA community analysis of total DNA
      extracted from the sponge tissue. The 16S rRNA gene sequences corresponding to
      group I crenarchaeotes and group II euryarchaeotes were recovered from R.
      odorabile tissue. The location of archaeal cells within the sponge tissue was
      investigated using fluorescently labeled oligonucleotide probes. The presence of
      Archaea was confirmed within all regions of the sponge tissue from R. odorabile,
      with a significantly higher number of archaeal cells located in the pinacoderm
      than the mesohyl region. This is the first report of euryarchaeaotes associated
      with marine sponges.

PMID- 14961333
TI  - Invasion without a bottleneck: Microsatellite variation in natural and invasive
      populations of the brown mussel Perna perna (L).
AB  - Population-level genetic diversity of the brown mussel Perna perna was
      investigated using nuclear microsatellite markers in 6 natural and 6 invasive
      populations. A total of 448 individuals from 12 populations spanning the natural
      and introduced ranges of the brown mussel were scored for 2 polymorphic
      microsatellite loci. Wright's hierarchical F statistics ( F(ST)), Hardy-Weinberg
      equilibrium, Nei's genetic distance, and other descriptive statistics were used
      to quantify geographic population subdivision, and to estimate the number of
      migrants per generation. F(ST) values (0.007-0.042) revealed that genetic
      partitioning among populations was low. Microsatellite data revealed a slight
      difference in observed heterozygosity and no statistically significant
      differences in expected heterozygosity or allelic diversity between natural and
      introduced populations. Effective numbers of migrants ( N(em)) per generation
      ranged from 6 to 35 individuals. The potential significance of an invasive
      species with high genetic variation in terms of the risk of establishment and
      conservation implications is discussed.

PMID- 14961334
TI  - Expression of aryl hydrocarbon receptor nuclear translocator (ARNT) isoforms in
      juvenile and adult rainbow trout tissues.
AB  - Whether and where rainbow trout aryl hydrocarbon receptor nuclear translocator
      (rtARNT) isoforms are expressed in juvenile and adult tissues of rainbow trout is
      unknown. Using reverse transcriptase polymerase chain reaction (RT-PCR),
      expression of the rtARNT(b) isoform messenger RNA was identified in day 19 and 23
      embryos, in day 27, 35, 39, and 42 sac fry, and in all adult tissues
      investigated. The rtARNT(a) isoform mRNA was expressed in all juvenile trout
      except day 42 sac fry and in all adult tissues except skeletal muscle. Western
      blot analysis and immunohistochemistry demonstrated that the rtARNT(b) protein
      was present in all juvenile trout and adult tissues investigated, except skeletal
      muscle, and was primarily localized to the nucleus. In contrast, rtARNT(a)
      protein was not detected at any developmental stage but was expressed in the
      adult gill. These results imply that rtARNT(b) is involved in signaling events at
      many developmental stages, while the functionality of the dominant negative
      rtARNT(a) is restricted.

PMID- 14961335
TI  - Genetic heterogeneity of the giant tiger shrimp (Penaeus monodon) in Thailand
      revealed by RAPD and mitochondrial DNA RFLP analyses.
AB  - Genetic diversity of the giant tiger shrimp (Penaeus monodon) collected from 5
      areas, Chumphon and Trat (Gulf of Thailand), and Phangnga, Satun, and Trang
      (Andaman Sea), was examined by randomly amplified polymorphic DNA (RAPD) and
      mitochondrial DNA (16S ribosomal DNA and an intergenic COI-COII) polymorphism. A
      total of 53 polymorphic fragments from UBC299, UBC273, and UBC268 was
      consistently scored across all samples. From the respective primers 26, 32, and
      30 genotypes were generated. A 260-bp RAPD fragment generated by the primer
      UBC268 was specifically observed in 95.8% of Trat P. monodon, suggesting that
      this RAPD could be used as a marker for comparing phenotypic performance of P.
      monodon from Trat and other geographic samples. In addition, 37 mtDNA composite
      haplotypes were observed from restriction analysis of the same P. monodon
      samples. High haplotype diversity (0.855) and nucleotide diversity (3.328%) of
      Thai P. monodon were observed. Population differentiation of P. monodon between
      the Andaman Sea and Gulf of Thailand was clearly illustrated by both techniques
      (P <.0001). Nevertheless, contradictory results on patterns of differentiation
      were observed between P. monodon within the Gulf of Thailand. Analysis of nuclear
      DNA polymorphism (RAPD) indicated a genetically significant difference between
      Chumphon and Trat ( P <.0001), whereas mtDNA polymorphism did not show
      differentiation between these samples (P =.0497). Under the presumption of
      selective neutrality of these markers, biased female gene flow between Trat and
      Chumphon P. monodon may exist and be responsible for an anomalous differentiation
      pattern between these geographic samples.

PMID- 14961336
TI  - Sterol and squalene content of a docosahexaenoic-acid-producing thraustochytrid:
      influence of culture age, temperature, and dissolved oxygen.
AB  - Thraustochytrid strain ACEM 6063, rich in omega-3 polyunsaturated fatty acids,
      was cultured at 15 degrees C and 20 degrees C in high (>40%) and low (<5%)
      dissolved oxygen (DO), and at 25 degrees C in low-DO media. Samples were taken 4,
      2, and 0 days before each culture reached peak biomass (T(-4), T(-2), and T(p),
      respectively). Twenty sterols, 13 of which were identified, were detected.
      Predominant were cholest-5-en-3 beta-ol, 24-ethylcholesta-5,22E-dien-3 beta-ol,
      24-methylcholesta-5,22E-dien-3 beta-ol, and 2 coeluting sterols, one of which was
      24-ethylcholesta-5,7,22-trien-3 beta-ol. These 4 sterols comprised 50% to 90% of
      total sterols. Cultures grown at high DO had simpler sterol profiles than those
      grown at low DO. Only the 4 sterols mentioned above were present at more than 3%
      of total sterols in high-DO cultures. In low-DO cultures, up to 6 additional
      sterols were present at more than 3% of total sterols. Culture age, temperature,
      and DO influenced squalene and sterol content. Total sterols (as a proportion of
      total lipids) decreased with increasing culture age. If organisms such as ACEM
      6063 are to be used for commercial production of lipid products for human
      consumption, both their sterol content and factors influencing sterol production
      need to be characterized thoroughly.

PMID- 14961337
TI  - Microsatellite analysis of 6-hour-old embryos reveals no preferential
      intraspecific fertilization between cupped oysters Crassostrea gigas and
      Crassostrea angulata.
AB  - Experimental examination of reproductive isolation is the first step in
      understanding hybridization processes. Here, we studied preferential
      fertilization between 2 cupped oyster taxa, Crassostrea angulata and Crassostrea
      gigas, as a potential prezygotic reproductive isolation. Early examination of
      sperm competition is now possible by molecular analysis of oyster embryos. This
      avoids the confounding effect of differential mortality during the larval stage.
      Six hundred embryos were sampled from 2 crosses. Three microsatellite loci were
      enough to determine without ambiguity the taxa of contributing sires of embryos.
      No evidence of preferential fertilization between gametes from the same taxa was
      shown. A significantly higher contribution of the C. gigas males was revealed
      with the C. angulata females, but not with the C. gigas females, which might
      suggest early heterosis or interaction differences between gametes. In the light
      of these results, natural hybridization between both taxa can be expected in
      cases of their geographical coexistence, as in the Southern European populations
      in which both taxa are in contact as a result of aquaculture development.

PMID- 14961338
TI  - Characterization of psychrotrophic bacteria in the surface and deep-sea waters
      from the northwestern Pacific Ocean based on 16S ribosomal DNA analysis.
AB  - Seventy-eight 4 degrees C-culturable bacteria were isolated using ZoBell 2216E
      medium from surface (0-200 m) and deep-sea (1000-9671 m) waters in the
      northwestern Pacific Ocean. Growth studies indicated that all 4 degrees C
      culturable bacteria were psychrotrophs. Six phylotypes were observed in the
      surface water samples and 8 phylotypes in the deep-sea waters. Phylogenetic
      characterization based on 16S ribosomal DNA sequence analysis of the
      representative phylotypes revealed that some bacterial genera, Pseudoalteromonas,
      Photobacterium, and Vibrio, were common to surface and deep-sea waters, and
      others, Pseudomonas and Halomonas, specifically occurred in surface water.
      Overall, the members of Vibrionaceae appear to be dominant in both habitats.

PMID- 14961339
TI  - Ontogeny of alpha-amylase gene expression in sea bass larvae (Lates calcarifer).
AB  - The enzymatic activities of alpha-amylase and its corresponding messenger RNA
      levels in developing sea bass (Lates calcarifer) larvae were studied from
      hatching until 27 days post hatching (dph). An increasing activity of amylase
      enzyme was measured until 5 dph, and the activity gradually decreased thereafter
      and reached a constant level by 12 dph. To achieve a better understanding of the
      molecular mechanisms underlying amylase expression, we have cloned and sequenced
      a 318-bp fragment of alpha-amylase complementary DNA. Based on this sequence, a
      real-time reverse transcriptase polymerase chain reaction technique to monitor
      the changes in the mRNA levels in the larvae was developed. A correlation between
      enzymatic activity and mRNA level of alpha-amylase could be demonstrated during
      the early development of sea bass larvae. This suggests that the changes in alpha
      amylase are controlled at least at the transcriptional level during early larval
      development of sea bass.

PMID- 14961340
TI  - Transgenic live-bearing fish and crustaceans produced by transforming immature
      gonads with replication-defective pantropic retroviral vectors.
AB  - Transgenic animals have been routinely produced by microinjecting or
      electroporating naked DNA into 1-cell-stage embryos or unfertilized eggs.
      However, these techniques are inapplicable to live-bearing fish and many
      crustacean species for which unfertilized or newly fertilized eggs are not
      readily obtainable. In the present study, replication-defective pantropic
      retroviral vectors carrying a reporter gene (neo(R) or beta-gal) were used to
      directly transform the immature ovary or testis of a live-bearing fish
      (Poeciliopsis lucida) and crayfish (Procambarus clarkii). The fraction of the
      progeny derived from these treated individuals shown to contain the neo(R)
      reporter gene by an assay based on polymerase chain reaction (PCR) was
      significant. The PCR-positive individuals were crossed with nontransgenic
      individuals, and about 50% of the resulting progeny carried the transgene,
      suggesting that the F(1) animals are germline transgenic. Integration of the
      transgenes was confirmed by detecting the junction fragments of the genomic DNA
      associated with transgene constructs. Expression of reporter genes was detected
      by a reverse transcription-nested PCR assay. These results showed that transgenic
      live-bearing fish and crustaceans could be easily produced by directly
      transforming the immature gonads with replication-defective pantropic retroviral
      vectors.

PMID- 14961341
TI  - Microsatellite genotyping of individual abalone larvae: parentage assignment in
      aquaculture.
AB  - In aquaculture, microsatellite DNA markers are used to genotype parental
      broodstock, to assess fertilization success, and to maintain pedigree information
      for selective breeding. In this study we genotyped individual Haliotis asinina
      larvae by analyzing a suit of polymorphic microsatellite loci. At least 10 loci
      can be analyzed from a single abalone veliger larva. We assayed 5 polymorphic
      loci to identify the parents of individual larvae produced in 3 separate crosses.
      In all cases, the parents of an individual veliger could be determined from as
      few as 3 loci. The microsatellite analysis revealed that, in each of our crosses,
      a single male fathered most of the veligers, despite efforts to normalize the
      amount of sperm contributed by competing males. These observations suggest that
      highly controlled breeding practices may be required to ensure that the genetic
      diversity of an abalone population produced for aquaculture is maintained at the
      level of diversity of the original broodstock.

PMID- 14961342
TI  - A centromeric satellite sequence in the Pacific oyster (Crassostrea gigas
      Thunberg) identified by fluorescence in situ hybridization.
AB  - A highly repetitive satellite sequence was previously identified in the Pacific
      oyster Crassostrea gigas Thunberg. The sequence has 168 bp per unit, present in
      tandem repeats, and accounts for 1% to 4% of the genome. We studied the
      chromosomal location of this satellite sequence by fluorescence in situ
      hybridization (FISH). A probe was made by polymerase chain reaction and
      incorporation of digoxigenin-11-dUTP. Hybridization was detected with fluorescein
      labeled antidigoxigenin antibodies. FISH signals were located at centromeric
      regions of 7 pairs of the Pacific oyster chromosomes. No interstitial site was
      found. Signals were strong and consistent on chromosomes 1, 2, 4, and 7, but weak
      or variable on chromosomes 5, 8, and 10. No signal was observed on chromosomes 3,
      6, and 9. Our results showed that this sequence is clearly a centromeric
      satellite, disputing its previous assignment to the telomeric and submetacentric
      regions of 2 chromosomes. No signal was detected in the American oyster
      (Crassostrea virginica Gmelin).

PMID- 14961343
TI  - Purification and Characterization of Mannitol-l-Phosphatase in the Red Alga
      Caloglossa continua (Ceramiales, Rhodophyta).
AB  - Purification of mannitol-l-phosphatase, an enzyme catalyzing the final step of
      mannitol biosynthesis, was first achieved in the mannitol-accumulating red alga
      Caloglossa continua (Okamura) King et Puttock. The enzyme was shown to be a
      monomer, since gel filtration and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis gave close values of apparent molecular weights of 28,500 and
      30,200, respectively. The protein exhibited an isoelectric point of 4.8. The
      substrate specificity for mannitol-l-phosphate (MIP) was very high, and that for
      K(m)(MIP) was 0.41 mM. The catalytic activity was optimal at pH 7.4. The enzyme
      was activated by Mg(2+), but was strongly inhibited by Ca(2+), NaF, N
      ethylmaleimide, and p-hydroxymercuribenzoic acid. Seawater levels of NaCl and
      physiological levels of mannitol also inhibited the activity by 50% or more.
      Changes in the concentrations of those ions and metabolites may regulate the
      biosynthesis of mannitol as an osmoregulant in vivo.

PMID- 14961344
TI  - The 60-kDa heat shock protein (HSP60) of the sea anemone Anemonia viridis: a
      potential early warning system for environmental changes.
AB  - Expression of heat shock proteins (HSPs) is often correlated with adaptation to
      environmental stress. We examined the role of HSP60 (60 kDa) in acclimatization
      to thermal stress in the sea anemone Anemonia viridis. Using monoclonal
      antibodies, we identified HSP60 in sea anemones for the first time, and showed
      that its expression varied with changes in seawater temperature (SWT). Anemonia
      viridis displayed high levels of HSP60 when extreme temperatures prevailed in
      stressful habitats such as tidal pools. Specimens sampled from different
      temperature layers in the same tidal pool differed in their levels of HSP60.
      Specimens from subtidal zones exhibited a seasonal pattern of expression of
      HSP60, according to the seasonal SWT. The level of HSP60 was significantly higher
      in the summer (SWT, 31 degrees C) than in other seasons throughout the year. This
      study suggests the use of HSP60 expression as a tool for stress detection in
      marine invertebrates.

PMID- 14961345
TI  - Identification of antihypertensive peptides from peptic digest of two microalgae,
      Chlorella vulgaris and Spirulina platensis.
AB  - The peptidic fractions that inhibited angiotensin I-converting enzyme (ACE) were
      separated from the peptic digests of 2 microalgae, Chlorella vulgaris and
      Spirulina platensis, by ion exchange chromatography and gel filtration. Oral
      administration of peptidic fractions into spontaneously hypertensive rats at 200
      mg/kg of body weight resulted in marked antihypertensive effects. Further
      separation of the peptidic fractions by ODS high-performance liquid
      chromatography furnished the following active peptides: Ile-Val-Val-Glu
      (inhibitory against ACE with an IC(50) of 315.3 microM), Ala-Phe-Leu (63.8
      microM), Phe-Ala-Leu (26.3 microM), Ala-Glu-Leu (57.1 microM), and Val-Val-Pro
      Pro-Ala (79.5 microM) from C. vulgaris; Ile-Ala-Glu (34.7 microM), Phe-Ala-Leu,
      Ala-Glu-Leu, Ile-Ala-Pro-Gly (11.4 microM), and Val-Ala-Phe (35.8 microM) from S.
      platensis.

PMID- 14961346
TI  - Inheritance characteristics of microsatellite DNA loci in experimental families
      of Japanese flounder Paralichthys olivaceus.
AB  - Allele segregating patterns of microsatellite DNA loci in 5 experimental families
      of Japanese flounder Paralichthys olivaceus and genotype frequencies for
      deviation from Hardy-Weinberg expectations (HWE) in natural P. olivaceus
      populations were studied to assess inheritability. Of the 12 microsatellite loci
      examined, 1 locus had a possibility of scoring errors of heterozygous individuals
      caused by unreproducible polymerase chain reaction amplifications of a particular
      allele. At the remaining 11 loci, almost all of alleles were segregated according
      to Mendelian transmission, and observed genotype frequencies in natural
      populations were consistent with HWE. The results demonstrated here would provide
      useful information supporting the suitability of these microsatellite loci as
      inheritable P. olivaceus genetic markers.

PMID- 14961347
TI  - Subunit C of the vacuolar-type ATPase from the vanadium-rich ascidian Ascidia
      sydneiensis samea rescued the pH sensitivity of yeast vma5 mutants.
AB  - A vanadium-accumulating ascidian, Ascidia sydneiensis samea, expresses vacuolar
      type H(+)-ATPases (V-ATPases) on the vacuole membrane of the vanadium-containing
      blood cells known as vanadocytes. Previously, we showed that the contents of
      their vacuoles are extremely acidic and that a V-ATPase-specific inhibitor,
      bafilomycin A(1), neutralized the contents of the vacuoles. To understand the
      function of V-ATPase in vanadocytes, we isolated complementary DNA encoding
      subunit C of V-ATPase from vanadocytes because this subunit has been known to be
      responsible for the assembly of V-ATPases and to regulate the ATPase activity of
      V-ATPases. The cloned cDNA was 1443 nucleotides in length, and encoded a putative
      384 amino acid protein. By expressing the ascidian cDNA for subunit C under the
      control of a galactose-inducible promoter, the pH-sensitive phenotype of the
      corresponding vma5 mutant of a budding yeast was rescued. This result showed that
      the ascidian cDNA for subunit C functioned in yeast cells.

PMID- 14961348
TI  - Transfection of eastern oyster ( Crassotrea virginica) embryos.
AB  - There is a need for research in disease resistance and microbial elimination in
      the eastern oyster Crassosostrea virginica. Gene transfer may lead to advances in
      this area, and a means of selecting transfected larvae would be useful. We
      transfected 3-hour-postfertilization embryos with the bacterial gene
      aminoglycoside phosphotransferase II (neo(r)), which confers resistance to
      neomycin and related antibiotics such as G418. The antibiotic G418 was examined
      as a potential selective agent. A neutral red assay was used to determine
      survival after 48 hours of exposure to various concentrations of G418 (0-4
      mg/ml). We examined the effects of electroporation and chemically mediated
      transfection of 3-hour-postfertilization embryos on survival to straight-hinge
      larvae. DNA alone was found to have no effect on survival (P >.05). For
      electroporation we found that increased voltage and pulse duration decreased
      survival (P <.05). Chemically mediated transfection did not significantly affect
      survival (P =.5172). Transgenic larvae were identified after electroporation and
      chemically mediated transfection. These larvae were reared for 24 hours and
      exposed to G418 at 0.3 mg/ml for 48 hours. Significant differences in survival
      between transfected and nontransfected larvae were detected for electroporation
      (P =.0147) and chemically mediated transfection (P =.037). Gene transfer was also
      confirmed with polymerase chain reaction and observation of expression of green
      fluorescent protein. This study documents the first successful insertion and
      expression of foreign DNA in eastern oyster larvae.

PMID- 14961349
TI  - Construction and use of a broad-host-range plasmid expressing the lamB gene for
      utilization of bacteriophage lambda vectors in the marine bacterium Vibrio
      harveyi.
AB  - The remarkable success of Escherichia coli as a model organism in molecular
      genetics was dependent, among other things, on its susceptibility to genetic
      manipulation. Many versatile and sophisticated genetic tools for molecular
      biology studies are derived from bacteriophage lambda. However, this
      bacteriophage is specific for E. coli, and thus lambda-based techniques have been
      restricted to this bacterium. Plasmids expressing the E. coli gene coding for
      bacteriophage lambda receptor were reported previously, and introduction of such
      plasmids into cells of some other bacteria made them sensitive to phage lambda
      infection. However, we found that these systems were not efficient for Vibrio
      harveyi, one of the most frequently investigated species of marine bacteria. Here
      we describe construction of a broad-host-range plasmid expressing the lamB gene.
      Introduction of this plasmid to V. harveyi cells and expression of lamB made this
      strain susceptible to bacteriophage lambda adsorption and lambda DNA injection.
      Foreign genetic material could be introduced into cells of this strain using a
      cosmid vector.

PMID- 14961350
TI  - IbpA/B small heat-shock protein of marine bacterium Vibrio harveyi binds to
      proteins aggregated in a cell during heat shock.
AB  - The IbpA and IbpB are 16-kDa Escherichia coli proteins belonging to a family of
      small heat-shock proteins (sHsps). According to the present model, based on the
      in vitro experiments, sHsps are molecular chaperones that bind and prevent
      aggregation of nonnative proteins during heat shock. Previously, we have shown
      that IbpA and IbpB bind to endogenous E. coli proteins aggregated intracellularly
      by heat shock, which can be separated from soluble proteins and membranes in
      sucrose density gradients (fraction S). In this work we have found that marine
      bacterium Vibrio harveyi contains a single sHsp which is strongly induced by heat
      shock and reacts with the anti-IbpA/B serum. The 26 amino-terminal amino acids of
      this sHsp bear high homology to E. coli IbpA and IbpB proteins (73% and 54%
      identity, respectively). Fraction S was prepared from heat-shocked cells of V.
      harveyi, it contained high amounts of the IbpA/B protein. This result indicates
      that the IbpA/B protein of V. harveyi binds to the proteins that aggregate in V.
      harveyi cells during heat shock.

PMID- 14961351
TI  - The first internal transcribed spacer (ITS-1) of ribosomal DNA as a molecular
      marker for phylogenetic and population analyses in crustacea.
AB  - The objective of the present study is to explore the feasibility of using the
      first internal transcribed spacer (ITS-1) of ribosomal DNA as a molecular marker
      for studying the interspecific and intraspecific genetic variations among
      crustaceans. We designed primers that could amplify ITS-1 from a majority of
      taxonomic groups of crustaceans. The gene was found to exhibit a high degree of
      length polymorphism among different groups, ranging from 182 bp in the barnacle
      Balanus amphitrite to approximately 820 bp in the spiny lobster Panulirus
      japonicus. With respect to differences between congeneric species, it was found
      that the ITS-1 sequences of 3 mitten crabs, Eriocheir sinensis, Eriocheir
      leptognathus, and Eriocheir formosa, exhibit 5.4% to 16.3% nucleotide divergence,
      suggesting that ITS-1 is informative for phylogenetic analysis at the species
      level. Yet there are extensive (0.9%-2.3%) variations within individual E.
      formosa, so that phylogenetic analyses could be obscured. ITS-1 was found to vary
      between 2 geographical populations of the shrimp Penaeus japonicus. The
      variations involved substitutions as well as insertions/deletions between shrimp
      from Australia and South China Sea. These results show that ITS-1 is highly
      divergent among different crustaceans and could be an appropriate marker for
      molecular systematic studies at the species and population levels, although the
      presence of intragenomic variation needs to be taken into consideration.

PMID- 14961352
TI  - The complete primary structure of molluscan shell protein 1 (MSP-1), an acidic
      glycoprotein in the shell matrix of the scallop Patinopecten yessoensis.
AB  - The complete primary structure of MSP-1, a major water-soluble glycoprotein in
      the foliated calcite shell layer of the scallop Patinopecten yessoensis, is
      reported. The full-length complementary DNA for MSP-1 isolated by polymerase
      chain reaction contained a sequence for a signal peptide of 20 amino acids
      followed by a polypeptide of 820 amino acids with calculated molecular mass of
      74.5 kDa. The deduced amino acid sequence of MSP-1 includes a high proportion of
      Ser (32%), Gly (25%), and Asp (20%), and the predicted isoelectric point is 3.2;
      in these respects, MSP-1 is a typical acidic glycoprotein of mineralized tissues.
      A repeated modular structure characterizes MSP-1, with a sequence unit between
      158 and 177 amino acids in length being repeated 4 times in tandem in the middle
      part of the protein. The repeated unit comprises 3 modules (SG, D, and K
      domains), each having a distinct amino acid composition and sequence. The SG
      domain is almost exclusively composed of Ser and Gly residues. The D domain is
      rich in Asp residues, potential N-glycosylation and phosphorylation sites. The K
      domain is rich in Gly residues and has a core of basic residues. The Asp residues
      are arranged more or less regularly in the D domains, exhibiting some repeated
      motifs such as Asp-Gly-Ser-Asp and Asp-Ser-Asp. Further, the 4 D domains indicate
      remarkable overall sequence similarities to each other. These observations
      suggest that the regular arrangements of COO(-) groups in the D domain side
      chains may be important for specific control of crystal growth.

PMID- 14961353
TI  - Molecular characterization of a mitochondrial DNA segment from the Japanese
      scallop (Patinopecten yessoensis): demonstration of a region showing sequence
      polymorphism in the population.
AB  - A 1.3-kb mitochondrial DNA segment from the Japanese scallop Patinopecten
      yessoensis was cloned and sequenced. This segment contained the transfer RNA(Met)
      gene and partial sequences of 2 ribosomal RNA genes, together with 2 separate
      noncoding regions (designated NcR1 and NcR2). The NcR regions derived from 78
      individuals cultured in Lake Saroma or Matsu Bay, were sequenced, and we found 15
      loci with sequence alterations including 13 substitutions, 1 deletion, and 1
      insertion (1 locus in NcR1, 14 loci in NcR2), and 17 haplotypes. Of the 17
      haplotypes, 10 were found in the Saroma population only, 3 in the Mutsu
      population only, and 4 in both populations. The gene diversity and nucleotide
      diversity values were, respectively, 0.87 and 0.0069 for the Saroma population,
      0.63 and 0.0040 for the Mutsu population, and 0.83 and 0.0203 overall. Thus the
      NcR segment was considered to have sufficient sequence variation for population
      genetic studies. The 16 variants of the NcR2 sequence were separated successfully
      by denaturing gradient gel electrophoresis, confirming the sequence variation in
      NcR2.

PMID- 14961354
TI  - Assessing the health of grass shrimp (Palaeomonetes pugio) exposed to natural and
      anthropogenic stressors: a molecular biomarker system.
AB  - We developed a molecular biomarker system (MBS) to assess the physiological
      status of Palaomenetes pugio (grass shrimp) challenged with exposure to heat
      stress, cadmium, atrazine, and the water-accommodating fraction of either diesel
      fuel or bunker fuel No. 2. The MBS assayed 9 specific cellular parameters of
      shrimp that are indicative of a nonstressed or stressed condition: heat-shock
      protein 60, heat-shock protein 70, alpha B-crystallin homologue, lipid peroxide,
      total glutathione level, ubiquitin, mitochondrial manganese superoxide dismutase,
      metallothionein, and cytochrome P-450 2E homologue. Using these 9 parameters, the
      MBS can distinguish between the responses to each stressor, and to the
      nonstressed control conditions. The MBS was able to determine the structural
      integrity of the cell as defined by protein turnover, protein chaperoning, and
      lipid composition via lipid peroxide levels, and the status of key metabolic
      processes such as cytoskeletal integrity and glutathione redox potential. This
      technology aids in the accurate diagnosis of the health of shrimp because the
      physiological significance of changes of each parameter is well known. This
      technology is particularly relevant for environmental monitoring because grass
      shrimp are used as key indicator species in many estuarine ecosystems. Finally,
      this system is easy to implement, precise, and can be quickly adapted to an
      automated high-throughput system for mass sample analysis.

PMID- 14961355
TI  - Molecular phylogeny and species identification of pufferfish of the genus
      Takifugu (Tetraodontiformes, Tetraodontidae).
AB  - The phylogenetic relationships and species identification of pufferfishes of the
      genus Takifugu were examined by use of randomly amplified polymorphic DNA (RAPD)
      and sequencing of the amplified partial mitochondrial 16S ribosomal RNA genes.
      Amplifications with 200 ten-base primers under predetermined optimal reaction
      conditions yielded 1962 reproducible amplified fragments ranging from 200 to 3000
      bp. Genetic distances between 5 species of Takifugu and Lagocephalus spadiceus as
      the outgroup were calculated from the presence or absence of the amplified
      fragments. Approximately 572 bp of the 16S ribosomal RNA gene was amplified,
      using universal primers, and used to determine the genetic distance values.
      Topological phylogenic trees for the 5 species of Takifugu and outgroup were
      generated from neighbor-joining analysis based on the data set of RAPD analysis
      and sequences of mitochondrial 16S rDNA. The genetic distance between Takifugu
      rubripes and Takifugu pseudommus was almost the same as that between individuals
      within each species, but much smaller than that between T. rubripes, T.
      pseudommus, and the other species. The molecular data gathered from both analysis
      of mitochondria and nuclear DNA strongly indicated that T. rubripes and T.
      pseudommus should be regarded as the same species. A fragment of approximately
      900 bp was amplified from the genome of all 26 T. pseudommus individuals examined
      and 4 individuals of intermediate varieties between T. rubripes and T.
      pseudommus. Of the 32 T. rubripes individuals, only 3 had the amplified fragment.
      These results suggest that this fragment may be useful in distinguishing between
      T. rubripes and T. pseudommus.

PMID- 14961356
TI  - Rapid isolation of DNA from fresh and preserved fish scales for polymerase chain
      reaction.
AB  - We developed a simple and inexpensive method to extract DNA from fresh and
      preserved fish scales. The procedure is based on boiling the scales in 5% Chelex
      100, followed by digestion with proteinase K and subsequent absorption of genomic
      DNA using silica. A single fresh scale from larger species (e.g., tilapia) or a
      few scales from smaller species (e.g., 4 scales from zebrafish) provide over 200
      ng of DNA, enough for at least 40 polymerase chain reaction amplifications. The
      procedure is applicable for DNA isolation not only from fresh and ethanol
      preserved scales, but also from dried and formaldehyde-treated samples, and thus
      might be useful for investigating specimens stored in museums and other
      collections. Since the removal of a few scales is a gentle means of sample
      collection, this technique will allow analysis of genetic diversity, mating
      systems, and parentage in populations of endangered or ornamental fish with
      minimal experimental influence.

PMID- 14961357
TI  - Influence of environmental salinity on messenger RNA levels of growth hormone,
      prolactin, and somatolactin in pituitary of the channel catfish (Ictalurus
      punctatus).
AB  - Pituitary growth hormone (GH), prolactin (PRL), and somatolactin (SL) messenger
      RNA levels in channel catfish (Ictalurus punctatus) were examined under various
      environmental and physiological conditions. Catfish were sampled following
      salinity challenge, during the winter (December) and spring or summer (April or
      July), and at different sizes (15-18 g, 620-664 g, and 956-1134 g). When catfish
      (956-1134 g) were transferred from freshwater to saline water containing 8 ppt
      NaCl, their plasma [Na(+)] increased significantly above values in the freshwater
      control group until they were transferred back to freshwater. Pituitary GH mRNA
      levels were low for the first 24 hours following transfer to saline water, but
      thereafter were significantly elevated above control values until the fish were
      transferred back to freshwater. Pituitary GH mRNA levels were highest in July and
      lowest in December. Growth hormone mRNA levels were also elevated in the size
      groups 15-18 g and 956-1134 g in July when compared with December values.
      Pituitary PRL mRNA levels increased for the first 24 hours following transfer to
      saline water (956-1134 g), but thereafter were significantly lower than control
      values until the fish were transferred back to freshwater. Pituitary PRL mRNA
      levels were highest in April and July and lowest in December, and were also
      elevated in the size groups 620-664 g and 956-1134 g. Pituitary SL mRNA levels
      were unaffected in catfish transferred to saline water; however, levels were
      significantly elevated in catfish of the 956-1134-g size group sampled in April
      when compared with December. These results suggest the involvement of GH in
      adaptation to brackish water and of PRL in adaptation to freshwater in the
      catfish, and seasonal and size-related differences in pituitary GH, PRL, and SL
      mRNA levels.

PMID- 14961358
TI  - Cloning, sequencing, and phylogenetic analysis of complementary DNA of novel
      cytochrome P-450 CYP1A in Japanese eel (Anguilla japonica).
AB  - Complementary DNA of cytochrome P-450 CYP1A, in addition to CYP1A1, has been
      isolated from Japanese eel (Anguilla japonica) liver treated with 3
      methylcholanthrene. The cDNA contained a 5' untranslated region of 66 bp, an open
      reading frame of 1554 bp coding for 517 amino acids and a stop codon, and a 3'
      untranslated region of 1166 bp. The predicted molecular weight of the Japanese
      eel CYP1A was approximately 58.5 kDa. The nucleotide sequence exhibited
      identities with the reported CYP1A1 sequences of 77% for Japanese eel, 75% for
      rainbow trout, 72% for scup, plaice, and butterfly fish, and 71% for toadfish.
      The deduced amino acid sequence exhibited identities with the reported CYP1A1
      sequences of 78% for Japanese eel, 77% for rainbow trout, 75% for scup, 74% for
      toadfish, 73% for plaice, and 72% for butterfly fish. The novel eel CYP1A
      obtained had less similarity to the other teleost CYP1A1 proteins (72%-78%) than
      that of the eel CYP1A1 (74%-80%). When compared with mammalian CYP proteins, the
      novel eel CYP1A was more similar to the CYP1A1 proteins (54%-56%) than to the
      CYP1A2 proteins (50%-53%). The phylogenetic tree of the teleost CYP1A genes
      constructed using the maximum likelihood method suggested that the novel eel
      CYP1A is ubiquitous among the Anguilliformes.

PMID- 14961359
TI  - Characterization of the myostatin gene in the gilthead seabream (Sparus aurata):
      sequence, genomic structure, and expression pattern.
AB  - We report on the sequence and expression analysis of the myostatin gene (MSTN) in
      the gilthead seabream Sparus aurata. A 2189-bp transcript was isolated, encoding
      an open reading frame (385 amino acids) that showed 74% to 60% protein similarity
      with other vertebrate myostatins. Phylogenetic analysis of MSTN and other related
      genes confirmed the evolutionary relationships of the isolated sequence. The
      complete sequences of two introns were also determined. Intron-exon boundaries
      were conserved when compared with those of mammalian MSTN genes, whereas intron
      size was smaller. Reverse transcriptase polymerase chain reaction on total RNA
      extracted from different tissues and developmental stages revealed MSTN
      expression in the skeletal muscle, but also in other tissues. The observed
      expression profile differed from that in mammals, suggesting possible additional
      functions of myostatin in the teleost fish.

PMID- 14961360
TI  - Rapid and simultaneous identification of body parts from the morphologically
      similar sharks Carcharhinus obscurus and Carcharhinus plumbeus (Carcharhinidae)
      using multiplex PCR.
AB  - Many commercially exploited carcharhinid sharks are difficult to identify to
      species owing to extensive morphological similarities. This problem is severely
      exacerbated when it comes to identifying detached shark fins, and the finless and
      headless shark carasses typically sold in markets. To assist in the acquisition
      of urgently needed conservation and management data on shark catch and trade, we
      have developed a highly streamlined approach based on multiplex polymerase chain
      reaction (PCR) that uses species-specific primers derived from nuclear ribosomal
      ITS2 sequences to achieve rapid species identification of shark body parts. Here
      we demonstrate the utility of this approach for identifying fins and flesh from
      two globally distributed, morphologically very similar carcharhinid sharks
      (Carcharhinus obscurus and Carcharhinus plumbeus) intensively targeted in
      fisheries worldwide, and often confused for each other even as whole animals. The
      assay is conducted in a 4-primer multiplex format that is structured to
      simultaneously achieve the following efficiency and cost-reduction objectives: it
      requires only a single-tube amplification reaction for species diagnosis, it
      incorporates an internal positive control to allow detection of false-negative
      results, and it is novel in that it allows species identification even when DNAs
      from two species are combined in the same tube during the PCR reaction. The
      latter innovation reduces the required effort for screening a set of unknown
      samples by 50%. The streamlined approach illustrated here should be amenable for
      use in a shark conservation and management context where large numbers of samples
      typically need to be screened; the approach shown may also provide a model for a
      rapid diagnostic method applicable to species identification in general.

PMID- 14961361
TI  - Effects of insert size on transposition efficiency of the sleeping beauty
      transposon in mouse cells.
AB  - Transposon vectors are widely used in prokaryotic and lower eukaryotic systems.
      However, they were not available for use in vertebrate animals until the recent
      reconstitution of a synthetic fish transposon, Sleeping Beauty ( SB). The
      reacquisition of transposability of the SB transposase fostered great enthusiasm
      for using transposon vectors as tools in vertebrate animals, particularly for
      gene transfer to facilitate accelerated integration of transgenes into
      chromosomes. Here, we report the effects of insert sizes on transposition
      efficiency of SB. A significant effect of insert size on efficiency of
      transposition by SB was found. The SB transposase enhanced the integration
      efficiency effectively for SB transposon up to approximately 5.6 kb, but lost its
      ability to enhance the integration efficiency when the transposon size was
      increased to 9.1 kb. This result indicates that the SB transposon system is
      highly applicable for transferring small genes, but may not be applicable for
      transferring very large genes.

PMID- 14961362
TI  - Genetic diversity of Ostreopsis ovata (Dinophyceae) from Malaysia.
AB  - The genus Ostreopsis is an important component of benthic and epiphytic
      dinoflagellate assemblages in coral reefs and seaweed beds of Malaysia. Members
      of the species may produce toxins that contribute to ciguatera fish poisoning. In
      this study, two species have been isolated and cultured, Ostreopsis ovata and
      Ostreopsis lenticularis. Analyses of the 5.8S subunit and internal transcribed
      spacer regions ITS1 and ITS2 of the ribosomal RNA gene sequences of these two
      species showed that they are separate species, consistent with morphological
      designations. The nucleotide sequences of the 5.8S subunit and ITS1 and ITS2
      regions of the rRNA gene were also used to evaluate the interpopulation and
      intrapopulation genetic diversity of O. ovata found in Malaysian waters. Results
      showed a low level of sequence divergence within populations. At the
      interpopulation level, the rRNA gene sequence distinguished two groups of
      genetically distinct strains, representative of a Malacca Straits group (isolates
      from Port Dickson) and a South China Sea group (isolates from Pulau Redang and
      Kota Kinabalu). Part of the sequences in the ITS regions may be useful in the
      design of oligonucleotide probes specific for each group. Results from this study
      show that the ITS regions can be used as genetic markers for taxonomic,
      biogeographic, and fine-scale population studies of this species.

PMID- 14961363
TI  - Growth Rate of the microalga Tetraselmis suecica changes the biochemical
      composition of Artemia species.
AB  - The impact of different microalgal semicontinuous cultures on growth and
      biochemical composition in the next link of the food chain was tested using the
      filter feeder Artemia species as a model. The marine microalga Tetraselmis
      suecica was cultured semicontinuously with renewal rates between 10% and 50% and
      used to feed Artemia. Microalgal cultures maintained with a low renewal rate that
      had biochemical composition similar to that of the stationary-phase cultures
      commonly used in aquaculture produced poor growth and survival and low food
      conversion efficiency compared to cultures maintained with a high renewal rate.
      Changes in the renewal rate in microalgal cultures also resulted in important
      changes in the gross biochemical composition of the filter feeder. The gross
      biochemical composition of the Artemia resembled that of the microalgae used as
      food except for total lipid content. The percentage of protein in the organic
      fraction of Artemia increased from 45% to 65% of the organic weight with
      increasing renewal rates in the microalgal cultures, while the carbohydrate
      percentage decreased under the same conditions. Higher renewal rates resulted in
      higher lipid percentages in the microalga, but in Artemia the percentage of
      lipids decreased from 19% of the organic weight with a renewal rate of 10%, to
      13% with a renewal rate of 50%. The percentage of all polyunsaturated fatty acids
      in Artemia, including 20:5n-3, increased slightly with increasing renewal rates
      in the microalgal cultures. Results emphasize the importance of controlling
      microalgal nutritional value for the success of aquaculture food chains in which
      filter feeders are involved.

PMID- 14961364
TI  - RFLP analysis of mitochondrial DNA to evaluate genetic variation in striped red
      mullet (Mullus surmuletus L.) and red mullet (Mullus barbatus L.) populations.
AB  - The genetic differentiation of striped red mullet (Mullus surmuletus) and red
      mullet (Mullus barbatus) was investigated in 6 Mediterranean populations of each
      species by means of restriction fragment length polymorphism analysis of
      mitochondrial DNA. Three segments amplified by polymerase chain reaction (control
      region, COI, and 12S-16S ribosomal RNA) were digested with 20 restriction
      endonucleases, revealing 71 haplotypes for M. surmuletus and 30 for M. barbatus.
      For the two species nucleotide diversity was equally distributed within and among
      populations, leading to N(ST) values of 0.545 and 0.500 for M. surmuletus and M.
      barbatus, respectively. However, intrapopulation and interpopulation genetic
      structuring appeared to be much higher for M. surmuletus than for M. barbatus
      (1.88% vs. 0.46% of mean intrapopulation nucleotide diversity; 1.94% vs. 0.47% of
      mean interpopulation nucleotide diversity; 0.055% vs. 0.002% of net
      interpopulation divergence). Furthermore, 81.69% of the haplotypes observed for
      M. surmuletus were unique, whereas 70.29% of M. barbatus individuals were grouped
      in 3 common haplotypes. Given that fishing pressure and population sizes are
      similar for both species, this differentiation could be attributed to differences
      in biological parameters and life histories between the two species, coupled with
      oceanographic conditions prevailing in the studied area.

PMID- 14961365
TI  - Polymorphisms of GA/GT microsatellite loci from Anguilla japonica.
AB  - Six novel microsatellite loci, containing (GA)(15?N17) or (GT)(10?N19) perfect
      tandem repeats, were isolated and characterized for the catadromous eel Anguilla
      japonica. The allelic size of the 6 loci ranged from 79 to 226 bp in length. All
      loci were polymorphic with a mean number of 14.7 alleles per locus and a mean
      heterozygosity of 0.67, suggesting higher polymorphism than that of freshwater
      and anadromous fishes, but lower than that of marine fishes. Genotype diversity
      of the 6 loci ranged from 0.22 to 0.61 with a mean value of approximately 0.5.
      Cross-species amplification showed that 5 of the 6 microsatellite primers proved
      to be useful in addressing questions of population genetics for all Anguilla
      species.

PMID- 14961366
TI  - Development in a primary cell culture of the marine sponge Ircinia muscarum and
      analysis of the polar compounds.
AB  - We have established a primary cell culture of the marine demosponge Ircinia
      muscarum. The culture was started from a cell suspension obtained by a
      combination of mechanical chemical means. Microbial contamination was controlled
      by the use of a pool of antibiotics. Optical density, rather than hemocytometer
      count, is suggested to monitor the cellular growth. Analysis of the chemical
      composition of I. muscarum cells revealed absence of sterols, showing that the
      cells were unable to biosynthesize sterols. When the medium was supplemented with
      cholesterol an increase of about 70% in the number of cells was observed. These
      results suggest that the classic mammalian nutrient medium was not satisfactory
      for I. muscarum cell growth, and sterols were needed to satisfy the membrane
      requirements.

PMID- 14961367
TI  - Amphitrite ornata, a marine worm, contains two dehaloperoxidase genes.
AB  - Amphitrite ornata, a terebellid polychaete, inhabits marine environments that are
      contaminated by biogenically produced halometabolites. These halogenated organic
      compounds are toxic and quite diverse. To survive in this environment, A. ornata
      produces a novel dehaloperoxidase (DHP I) that detoxifies haloaromatic compounds.
      In this study we identified and characterized two dehaloperoxidase genes,
      designated dhpA and dhpB, from an A. ornata complementary DNA library. The
      deduced amino acid sequences (DHP A and DHP B) of the two dhp genes both contain
      137 amino acid residues, but they differ at 5 amino acid positions. Allelic
      variation was observed for both genes as well. Polymerase chain reaction
      restriction fragment length polymorphism assays of genomic DNA from 19 in
      individuals showed that each individual contains both the dhpA and the dhpB
      genes. Therefore, the two types of DHP are encoded by separate genes and are not
      alleles of a single gene. Furthermore, DHP A and DHP B may have different
      substrate specificities since they have amino acid differences in the active
      site.

PMID- 14961368
TI  - Microsatellite variation among red snapper (Lutjanus campechanus) from the Gulf
      of Mexico.
AB  - Allelic variation at a total of 20 nuclear-encoded microsatellites was examined
      among adult red snapper (Lutjanus campechanus) sampled from 4 offshore localities
      in the Gulf of Mexico. The number of alleles at the 20 microsatellites ranged
      from 5 to 20; average (+/- SE) direct count heterozygosity values ranged from
      0.148 +/- 0.025 to 0.902 +/- 0.008. No significant departures from expectations
      of Hardy-Weinberg equilibrium were found for any locus within samples, and
      genotypes at pairs of microsatellites appeared to be randomly associated, i.e.,
      in genotypic equilibrium. Tests of homogeneity in allele distributions among the
      4 localities were nonsignificant for 19 of the microsatellites. Allele
      distribution at microsatellite Lca 43 was heterogeneous among localities before
      (but not after) Bonferroni corrections for multiple tests executed
      simultaneously. Tests of homogeneity in the distribution of individual alleles at
      Lca 43 gave similar results: one low frequency allele was distributed
      heterogeneously among samples before, but not after, Bonferroni correction.
      Molecular analysis of variance indicated that more than 99% of variation at each
      microsatellite was distributed within sample localities. These results generally
      are consistent with the hypothesis of a single population (stock) of red snapper
      in the northern Gulf of Mexico.

PMID- 14961369
TI  - Isolation and characterization of four microsatellite loci in the tidewater goby
      (Eucyclogobius newberryi).
AB  - The first microsatellite loci for the endangered tidewater goby Eucyclogobius
      newberryi are described. A partial tidewater goby genomic library was constructed
      in pUC19 plasmid. Microsatellite-containing clones were isolated, sequenced, and
      amplified. Out of 12 positive clones sequenced, 3 were polymorphic and proved
      useful in a preliminary genetic screen of 3 well-separated populations (50
      individuals each) along the central California coast. The number of alleles per
      locus ranged from 2 to 3. This initial study suggests a population bottleneck had
      occurred in one of the populations.

PMID- 14961370
TI  - Genetic transformation system for a psychrotrophic deep-sea bacterium: isolation
      and characterization of a psychrotrophic plasmid.
AB  - A versatile system that permits genetic manipulation of a psychrotrophic deep-sea
      bacterium, Pseudoalteromonas sp. PS1M3, has been developed. A cryptic indigenous
      plasmid, pPS1M3, of 3.1 kb from the above strain was isolated and characterized.
      The nucleotide sequence analysis of plasmid pPS1M3 revealed the presence of one
      open reading frame, and its deduced amino acid sequence was identified as the
      essential protein for plasmid maintenance. Transformation with the pPS1M3
      harboring antibiotic resistance genes by electroporation was fully successful
      using the pPS1M3-cured strain as a host. This plasmid was quite stable under
      nonselective culture conditions for about 100 generations at 4 degrees C. The
      copy number of this plasmid in the cell was about 5 copies per chromosome.

PMID- 14961371
TI  - A simple, reliable, and fast protocol for thraustochytrid DNA extraction.
AB  - DNA extraction of thraustochytrids, common marine unicellular organisms, is
      usually accomplished by either the cetyltrimethylammonium bromide (CTAB) or
      proteinase K protocols. A novel lysis buffer protocol for thraustochytrid total
      DNA extraction is described. The average isolated total DNA is 20 to 40 kb, and
      DNA samples are suitable for a variety of uses including 18S-ribosomal DNA
      polymerase chain reaction, restriction enzyme digestions, and amplified fragment
      length polymorphism analyses. The new protocol is also faster than the other
      protocols.

PMID- 14961372
TI  - Formation of infectious pancreatic necrosis virus-like particles following
      expression of segment A by recombinant semliki forest virus.
AB  - Segment A of the Sp strain (a Norwegian field isolate) of infectious pancreatic
      necrosis virus (IPNV) was amplified by reverse transcriptase polymerase chain
      reaction in two stages from RNA isolated from infected cells, and cloned into the
      Semliki Forest virus (SFV) expression vector pSFV1. Expression and correct
      processing of IPNV proteins was confirmed by transfection of RNA transcribed from
      this plasmid into BHK cells. This clone was then used to produce recombinant
      replication-defective SFV particles (rSFV) expressing the IPNV segment A.
      Immunofluorescence studies with conformation-dependent monoclonal antibodies to
      IPNV confirmed that the recombinant proteins produced after infection of the
      salmonid cell line CHSE-214 with such rSFV retain their antigenicity. Infection
      of the CHSE cells with the rSFV resulted in the formation of IPNV-like particles,
      which were similar in size and morphology to IPNV.

PMID- 14961373
TI  - Neuropeptide Y sequence and messenger RNA distribution in channel catfish
      (Ictalurus punctatus).
AB  - The action of neuropeptide Y (NPY) on food intake is of interest for the
      enhancement of growth of channel catfish (Ictalurus punctatus) for aquaculture.
      We sequenced 795 bp of complementary DNA (including 288 bp of open reading frame
      that encompassed the signal peptide, mature peptide, and carboxy-terminal
      peptide) from catfish brain NPY (GenBank accession number AF267164) and
      identified untranslated regions of the gene. We found high identity (88%-91%) of
      the amino acid sequence of the translated, mature protein with other fish NPYs.
      Using Northern blotting and reverse transcriptase polymerase chain reaction, we
      found NPY gene expression in the hypothalamus, myelencephalon, telencephalon, and
      optic tectum of the brain, but not the cerebellum or the pituitary gland. NPY
      expression was also found in immature ovary. Our results highlight the conserved
      nature of NPY in vertebrate systems, and the probes developed in this work will
      facilitate physiological and genetic studies of feeding and growth in channel
      catfish.

PMID- 14961374
TI  - Multiple tissue transformation in adult zebrafish by gene gun bombardment and
      muscular injection of naked DNA.
AB  - The efficiency of two direct gene transfer methods, gene gun (or particle
      bombardment) and intramuscular injection, in transforming adult zebrafish tissues
      in vivo was examined by a noninvasive approach using green fluorescent protein
      (GFP) reporter gene driven by the ubiquitously expressed human cytomegalovirus
      promoter. Particle bombardment of adult zebrafish caused internalization and
      expression of the plasmid only in the superficial layer such as epithelial cells,
      pigment cells, endothelial cells, and neurons, whereas direct injection primarily
      transformed muscle fibers of several bundles near or around the injection site.
      Expression was also evident in several nonmuscle tissues, such as skin epithelia,
      pigment cells, blood vessel cells, and neuron-like cells. GFP expression
      persisted for more than 50 days with both methods. These observations indicate
      the potential of these methods for functional analysis of tissue-specific
      promoters, delivery of DNA vaccine, and muscular expression of other useful
      genes.

PMID- 14961375
TI  - Screening and characterization of fructosyl-valine-utilizing marine
      microorganisms.
AB  - We describe the isolation of microorganisms utilizing fructosyl-amine (Amadori
      compound) from the marine environment and of fructosyl-amine oxidase from a
      marine yeast. Using fructosyl-valine (Fru-Val), a model Amadori compound for
      glycated hemoglobin, we isolated 12 microbial strains that grow aerobically in a
      minimal medium supplemented with Fru-Val as the sole nitrogen source. Among these
      strains, a yeast strain identified as Pichia sp. N1-1, produced a Fru-Val
      oxidizing enzyme. The enzyme was purified in its active form, a single
      polypeptide water-soluble protein of 54 kDa by gel electrophoresis, producing
      H(2)O(2) with the oxidation of Fru-Val. By its substrate specificity, the enzyme
      was categorized as a novel fructosyl-amine oxidase. This is the first study on
      the isolation of microorganisms utilizing fructosyl-amine in the marine
      environment and of fructosyl-amine oxidase from budding yeast.

PMID- 14961376
TI  - Genetic diversity and molecular markers of cupped oysters (genera Crassostrea,
      Caccostrea, and Striostrea) in Thailand revealed by randomly amplified
      polymorphic DNA analysis.
AB  - Genetic diversity and species-diagnostic markers of 5 oysters in Thailand,
      Crassostrea belcheri (Sowerby, 1871), Crassostrea iredalei (Faustino, 1932),
      Saccostrea cucullata (Born, 1778), Saccostrea forskali (Gmelin, 1791), and
      Striostrea Parastriostrea) mytiloides (Lamarck, 1819), were investigated by
      randomly amplified polymorphic DNA (RAPD) analysis. In a total, 135, 127, and 108
      genotypes were observed from primers OPA09, OPB01, and OPB08 (Operon Technologies
      Inc., kits A and B), and 131 and 122 genotypes from primers UBC210 and UBC220
      (University of British Columbia), respectively. Two hundred fifty-four
      reproducible and polymorphic fragments (200-2500 bp in length) were generated
      across the 5 investigated species. The average number of bands per primer varied
      between 12.4 and 32.2. The percentage of polymorphic bands within Crassostrea
      (53.23%-77.67%) was lower than that within Saccostrea and Striostrea oysters
      (86.21%-99.36%). Nine, species-specific markers were found in C. belcheri, 4 in
      C. iredalei, and 2 in S. cucullata. The mean of a ratio between the number of
      genotypes generated by each primer and the number of investigated specimens of C.
      belcheri (0.58) was lower than that of the remaining species (0.90-1.00). Genetic
      distances between pairs of oyster samples were between 0.105 and 0.811. A
      neighbor-joining tree indicated distant relationships between Crassostrea and
      Saccostrea oysters, but closer relationships were observed between the latter and
      Striostrea mytiloides.

PMID- 14961377
TI  - Molecular cloning and genomic structure of a gene encoding interferon regulatory
      factor in the pufferfish (Fugu rubripes).
AB  - Interferon regulatory factors (IRFs) are a large family of transcription factors
      involved in regulating the transcriptional response of vertebrates to interferons
      and viral infection. In this report we describe the cloning and genomic
      organization of an IRF gene from the pufferfish (Fugu rubripes). The fugu IRF
      gene spans 2.7 kb from the transcription start site to the polyadenylation
      signal. It consists of 10 exons and 9 introns and encodes a protein of 296 amino
      acids. The overall amino acid sequence of fugu IRF displays 55% identity to
      flounder IRF and approximately 44% identity to avian and mammalian IRF-1 and IRF
      2. On the basis of the genomic structure and the absence of a transcriptional
      repression domain, we conclude that the fugu IRF is a member of the IRF-1 family.
      The fugu IRF gene is expressed in a wide range of tissues. While a single
      transcript of 1.4 kb was detected in most tissues, several larger transcripts
      generated using alternative polyadenylation signals were found in the gills.

PMID- 14961378
TI  - Polymerase chain reaction in detection of Gymnodinium mikimotoi and Alexandrium
      minutum in field samples from southwest India.
AB  - Polymerase chain reaction (PCR) primers were constructed for the detection of two
      toxic dinoflagellate species, Gymnodinium mikimotoi and Alexandrium minutum. The
      primers amplified a product of expected size from cultured cells of G. mikimotoi
      and A. minutum. The species-specific primers targeting G. mikimotoi did not yield
      any product with a wide range of other cultured algae used as negative controls.
      Primers designed for A. minutum were species-group-specific since it PCR yielded
      a product from the closely related species A. ostenfeldii and A. andersonii, but
      not from other species of this genus tested. The confirmation of PCR products was
      performed by digestion of the products with restriction enzymes. Sensitivity
      analyses of the primers on DNA template from cultured cells was positive by PCR
      at a DNA template concentration of 1.5 x 10(-4) ng/microl (0.3 cells/L) for A.
      minutum, and at a DNA concentration of 2.5 x 10(-2) ng/microl (697 cells/L) for
      G. mikimotoi. The PCR method for detection of G. mikimotoi and A. minutum was
      applied on field samples collected with a plankton net. Gymnodinium mikimotoi
      could be detected in 11 field samples by microscopy, and all these field samples
      were positive by PCR. The cell counts of G. mikimotoi in simultaneously collected
      water samples ranged from 306 to 2077/L. Alexandrium minutum could be detected by
      microscopy in 3 different field samples. The cell counts in water samples
      collected at the same time as the net samples ranged from 115 to 1115 cells/L.
      Alexandrium minutum was detected by PCR in these field samples, with the
      exception of the sample displaying the lowest cell count (115 cells/L). Plankton
      samples that were negative by microscopy for any of the two target species were
      also negative by PCR. All the PCR products from field samples were confirmed by
      restriction enzyme digestion. The application of PCR-based detection of harmful
      algal bloom species for aquaculture and monitoring purposes in natural field
      samples is discussed.

PMID- 14961379
TI  - Sequencing and amplified restriction fragment length polymorphism analysis of
      ribonucleotide reductase large subunit gene of the white spot syndrome virus in
      blue crab (Callinectes sapidus) from American Coastal Waters.
AB  - In the present study, the existence of white spot syndrome virus (WSSV) in blue
      crab (Callinectes sapidus) collected from 3 different American coastal waters
      (New York, New Jersey, and Texas) was confirmed by 2-step diagnostic polymerase
      chain reaction and in situ hybridization analysis. When geographic isolates were
      also compared using a gene that encodes the WSSV ribonucleotide reductase large
      subunit RR1 (WSSV rr1), a C(1661)-to-T point mutation was found in the New Jersey
      WSSV isolated. This point mutation, which resulted in the creation of an
      additional RsaI endonuclease recognition site, was not found in the WSSV from the
      New York and Texas blue crab samples, or in the WSSV Taiwan isolate, or in any of
      the other WSSV geographical isolates for which data are available. WSSV rr1
      specific RsaI amplified restriction fragment length polymorphism of an amplified
      1156-bp fragment thus distinguished the New Jersey blue crab samples from the
      other WSSV isolates.

PMID- 14961380
TI  - Postmortem degradation of white fish skeletal muscle (sea bass, Dicentrarchus
      labrax): fat diet effects on in situ dystrophin proteolysis during the prerigor
      stage.
AB  - All during fish postmortem evolution, structural muscle proteins are targets for
      various proteases. During the prerigor period (24 hours at 4 degrees C for sea
      bass), cytoskeletal proteins are affected by the first proteolytic events. These
      cleavages disrupt connections between myofibrils and the extracellular matrix,
      induce segmentation of myofibril cores, and modify the rheological properties of
      tissue. Dystrophin, a cytoskeletal actin-binding protein, is a relevant in situ
      marker for muscular proteolysis in the prerigor period. The immunodetection of
      dystrophin allowed the monitoring of early proteolysis during fish storage. Using
      antidystrophin antibodies directed toward the carboxy-terminal region, a highly
      sensitive domain exposed to calpain activity, we showed that proteolysis kinetics
      are strongly influenced by the muscular lipid content. In particular, comparison
      between low-fat diets (11.3% lipid) and high-fat diets (30% lipid), used during
      sea bass farming (90 days), revealed a faster proteolysis rate during the first 8
      hours of storage at 0 degrees C with the high-fat diet. The origin of this faster
      proteolysis is discussed on the basis of a possible activation or translocation
      of calpains related to lipid accumulation in muscle fibers and cytoskeleton
      alterations.

PMID- 14961381
TI  - Microbial communities and exopolysaccharides from Polynesian mats.
AB  - Microbial mats present in two shallow atolls of French Polynesia were
      characterized by high amounts of exopolysaccharides associated with cyanobacteria
      as the predominating species. Cyanobacteria were found in the first centimeters
      of the gelatinous mats, whereas deeper layers showing the occurrence of the
      sulfate reducers Desulfovibrio and Desulfobacter species as determined by the
      presence of specific biomarkers. Exopolysaccharides were extracted from these
      mats and partially characterized. All fractions contained both neutral sugars and
      uronic acids with a predominance of the former. The large diversity in
      monosaccharides can be interpreted as the result of exopolymer biosynthesis by
      either different or unidentified cyanobacterial species.

PMID- 14961382
TI  - Changes in tissue cellularity are associated with growth enhancement in
      genetically modified arctic char (Salvelinus alpinus L.) carrying recombinant
      growth hormone gene.
AB  - Biochemical and histological analyses were used to study the number and size of
      cells (cellularity) in tissues of fast-growing, genetically modified Arctic char
      (Salvelinus alpinus L.), overexpressing sockeye salmon (Oncorhynchus nerka)
      growth hormone gene (OnGH1). DNA contents of muscle, heart, and liver were
      compared in transformed, sibling (age control) and 1 year older (size control)
      char. Total white muscle cross-sectional area, white muscle fiber number, and
      total nuclei number within the muscle tissue were determined from one complete
      half-section of each fish. The analyzed tissues responded differently to growth
      hormone overproduction. In muscle tissue of OnGH1-transformed char, the enhanced
      growth was clearly associated with proliferation of muscle cells (hyperplasia),
      whereas in heart tissue both cell proliferation and increase in cell size
      (hypertrophy) were enhanced. The relative DNA concentration in the liver of
      transformed char was significantly greater than that of control fish, suggesting
      reduction in size of hepatic cells.

PMID- 14961383
TI  - Characterization of microsatellites in the IGF-2 and GH genes of Asian seabass
      (Lates calcarifer).
AB  - Four microsatellites were identified by screening the DNA sequences of Asian
      seabass (Lates calcarifer) deposited to GenBank. Two markers each are located in
      the growth hormone gene (GH) and in the insulin-like growth factor II gene ( IGF
      2), respectively. The markers were characterized by genotyping 34 Asian seabass
      individuals. All 4 microsatellites showed polymorphism: the number of alleles per
      locus ranged from 2 to 11 (average, 5.0), while the expected heterozygosity
      ranged from 0.51 to 0.85 (average, 0.63) at the 4 loci. Cross-priming with all 4
      primer pairs was tested in species belonging to 5 different genera, but no bands
      were amplified. These microsatellites are the first genomic DNA markers
      characterized in L. calcarifer; thus they may be valuable for research and
      aquaculture production of this species.

PMID- 14961384
TI  - Changes in ubiquitin conjugates and Hsp72 levels during arm regeneration in
      echinoderms.
AB  - All organisms show a common defensive mechanism that results in the expression of
      conserved heat shock proteins (Hsps). These proteins function in a wide range of
      stressful conditions. We have monitored their levels in species of regenerating
      echinoderms with different mechanisms of regeneration and from different
      geographical locations. The effect of an artificial higher temperature on
      expression of Hsps was also studied. Two stress proteins (Hsp72 and ubiquitin)
      that are important in processes such as development and protein degradation were
      investigated. Using Western blot analysis and immunocytochemistry, we found
      significant changes in the level (Hsp72) and pattern of conjugation (ubiquitin)
      that corresponded with the repair phase (early regenerative stages) and with the
      later growth and regeneration of new tissues. Animals from the intertidal
      environment showed a distinctly sustained expression pattern of Hsp72 compared
      with benthic animals which suggests a functionally adaptative and dynamic stress
      response program.

PMID- 14961385
TI  - Quantitative TaqMan PCR without a real-time thermal cycler: an assay for fish
      insulin-like growth factor I messenger RNA.
AB  - The reverse transcriptase-polymerase chain reaction, more commonly known as RT
      PCR, has become a widely used tool in molecular biology and is now frequently
      used in monitoring gene expression levels. A number of variations in the RT-PCR
      technique now exist including TaqMan PCR (5' nuclease assay), which is a useful
      nonisotopic detection method for the quantification of PCR products. To monitor
      the formation of these fluorescent amplification products a "real-time" thermal
      cycler is normally required. In this study, repeated scanning of PCR products in
      a 96-well plate format showed that a conventional fluorescent plate reader can be
      used to generate similar results. To demonstrate the power of this approach, the
      nutritional regulation of insulin-like growth factor I (IGF-I) was investigated
      in a marine finfish, the snapper (Pagrus auratus). Hepatic IGF-I messenger RNA
      levels were shown to significantly decrease after 2 weeks of fasting and returned
      to fed control levels on refeeding. These results demonstrated that a real-time
      PCR machine was not required to generate this type of quantitative data and that
      this technology can be adapted for use in most molecular biology laboratories.

PMID- 14961386
TI  - Direct evidence for Mendelian inheritance of the variations in the ribosomal
      protein gene introns in yellowfin tuna (Thunnus albacares).
AB  - Restriction fragment length polymorphism found in the S7 ribosomal protein gene
      introns of yellowfin tuna (Thunnus albacares) was compared between a single pair
      of parents and their offspring. The sizes of the first intron ( RP1) and second
      intron ( RP2) amplified by polymerase chain reaction were 810 bp and 1400 bp,
      respectively. The dam and sire had different restriction types from one another
      in HhaI and RsaI digestions for RP1 and in DdeI, HhaI, and ScrFI digestions for
      RP2. Putative genotypes in both introns of 64 larvae were found to be segregated
      in Mendelian proportions. Genotype distributions in a wild yellowfin tuna sample
      ( n = 34) were in Hardy-Weinberg proportions, and observed heterozygosity ranged
      from 0.149 to 0.388. This study presents novel Mendelian markers, which are
      feasible for tuna population genetic study and pedigree analysis.

PMID- 14961387
TI  - Fibroblast growth factor inhibits expression of neural markers in cultures of
      zebrafish early embryo cells.
AB  - Basic fibroblast growth factor (FGF) regulation of developmental markers in cell
      cultures derived from early zebrafish embryos was examined with the goal of in
      vitro culture of zebrafish embryonic stem cells and gaining an understanding of
      extracellular influences on early embryonic development. Markers were
      stem/primordial germ cell markers pou-2 and vas, neural markers zp-50, pax[zf-a],
      en-3, and wnt-1, and mesodermal markers gsc and myoD. Previously we had shown
      that FGF prevents the development of zebrafish pigment cells in vitro. In our
      culture system, FGF reduced expression of neural-specific markers, possibly
      implicating the FGF family in suppression of early neural cell development.
      Exposure to FGF for 24 hours at the time of seeding the cells was sufficient to
      suppress neural marker expression for a subsequent 4 days of culture, while
      absence of FGF for the first 24 hours of culture nullified the effect of FGF
      added subsequently. FGF predictably increased expression of gsc and myoD. Vas
      expression was unaffected, while pou-2 expression decreased with time in culture
      in the presence or absence of FGF. However, in situ hybridization identified a
      subpopulation of cells expressing pou-2, suggesting the possible continued
      existence of undifferentiated stem cells in the cultures.

PMID- 14961388
TI  - Characterization and quantification of chitosan extracted from nacre of the
      abalone Haliotis tuberculata and the oyster Pinctada maxima.
AB  - This study was performed to characterize and quantify chitosan by simple
      physicochemical methods (infrared spectroscopy and potentiometric measurements).
      These procedures were validated with well-characterized chitosan before being
      used to investigate chitosan in nacre of the abalone Haliotis tuberculata and of
      the giant oyster Pinctada maxima. Potentiometric study revealed a chitosan
      extract from the nacre of H. tuberculata with a degree of deacetylation of around
      88% and an intrinsic pK of 6.5. According to infrared and potentiometric data, a
      low yield (eta) of extraction was calculated (eta = 0.064%). For experiments
      performed on the nacre of P. maxima, and in spite of more stringent deacetylation
      conditions, results suggested that a chitin-protein complex (eta = 0.053%) was
      isolated rather than chitosan.

PMID- 14961389
TI  - Analysis of microsatellite DNA polymorphisms in rockfish Sebastes thompsoni and
      application to population genetics studies.
AB  - Population differentiation and relationships among 6 natural rockfish populations
      collected from northern coastal seas around Japan were assayed using
      microsatellite DNA loci. Seven loci examined were polymorphic in all populations.
      The number of alleles per locus ranged from 6.7 to 9.3, and the average of
      observed and expected heterozygosity ranged from 0.63 to 0.68, and from 0.66 to
      0.69, respectively. The observed genotype frequencies at each locus were almost
      in agreement with Hardy-Weinberg expectations with two exceptions (P <.05). The
      allele frequencies of 16 population pairs were significantly different (P <.05).
      Genetic distance (D(A)) between 6 populations ranged from 0.03 to 0.08. According
      to a neighbor-joining tree generated from the D(A) values, the 6 populations fell
      into 3 clusters. These clusters were correlated with the geographical positions
      of each population; larval dispersions due to water current were also found to
      have an effect on these results.

PMID- 14961390
TI  - Reconstitution of sperm nuclei of zebrafish (Danio rerio) in Xenopus egg
      extracts.
AB  - Cell-free extracts of Xenopus eggs cause cyclic change in permeabilized sperm
      nucleus, nuclear envelope breakdown, chromosome condensation, and reformation of
      nuclei. In this study, the ability of cell-free extracts to cause similar changes
      in zebrafish sperm was examined. When lysolecithin-treated sperm from zebrafish
      were incubated in Xenopus egg extracts, a series of changes in sperm nuclear
      morphology were observed periodically. These changes correlated with maturation
      promoting factor (MPF) activity. Furthermore, sperm nuclei of zebrafish
      replicated DNA during reconstitution in Xenopus egg extracts. These results
      showed that cell-free extracts of Xenopus egg possess the ability to cause cell
      cycle-dependent changes in zebrafish sperm, implying the possibility of
      generating transgenic zebrafish in a similar way to transgenic Xenopus.

PMID- 14961391
TI  - Genetic relatedness and variability in inbred and wild populations of the
      solitary ascidian Ciona intestinalis revealed by arbitrarily primed polymerase
      chain reaction.
AB  - As the first step in the establishment of inbred Ciona intestinalis strains, the
      genetic backgrounds of several local populations were evaluated on the basis of
      comparing 313 random amplified polymorphic DNA (RAPD) loci. Cluster analyses of
      individuals indicated that this species has local genetic characteristics,
      although various genetic distances among the populations were relatively low. The
      bulked RAPD analyses revealed that populations from Torihama and from Onagawa
      were the most distantly related among the 7 populations examined, suggesting that
      these two populations are the best candidates for outbreeding. Successive
      inbreeding in the laboratory was achieved using the Onagawa population. Although
      the genetic similarity of the F(4) progeny became distinctly higher than that of
      natural populations, F(5) progeny did not survive, presumably owing to homozygous
      lethal alleles.

PMID- 14961392
TI  - A new isolation method for labyrinthulids using a bacterium, Psychrobacter
      phenylpyruvicus.
AB  - A new isolation method for labyrinthulids, marine microbes with spindle-shaped
      vegetative cells and gliding movement, is presented. The method for isolating
      labyrinthulids has been found to be more difficult and less reproducible than
      that for thraustochytrids, classified in the same order. So far serum seawater
      agar fortified with antibiotics has been proposed to be the best for isolation of
      labyrinthulids. The method presented here involves placing plant samples on an
      agar medium on which a marine bacterium, Psychrobacter phenylpyruvicus, has been
      grown. The new method, which utilizes fallen mangrove leaves as source material,
      was more than twice as effective as isolation agar medium without the bacterium.
      The increased effectiveness appears to derive partly from the bacterial colonies'
      delaying extension of fungal mycelium. The bacterium was more effective for the
      isolation of labyrinthulids than either the bacterium Shewanella sp. or the yeast
      Rhodotorula rubra.

PMID- 14961393
TI  - Photosynthesis of Prochloron as affected by environmental factors.
AB  - The effects of light intensity, pH, temperature, and UV irradiation on the
      photosynthetic rate of Prochloron isolated from the ascidian host Lissoclinum
      patella, collected from Palau, were examined. Photosynthesis increased with light
      intensity with saturation at 500 micromol/m(2) per second. It was maximum at pH 8
      to 9 but almost completely suppressed below pH 7. The optimum temperature was 35
      degrees to 40 degrees C, but the photosynthesis was absent at < or =20 degrees C
      and at 45 degrees C. It was recovered when the symbiont was transferred from 1
      hour of incubation at < or =20 degrees C to 35 degrees C but not when transferred
      from incubation at 45 degrees C. Ultraviolet irradiation severely inhibited the
      photosynthesis of Prochloron in isolation but not in vivo. This protection was
      brought about by the tunic covering the ascidian colony, which contains UV
      absorbing mycosporine-like amino acids. These results indicate that the
      characteristic condition of the tropical marine environment largely determines
      the ecological distribution of Prochloron, and the ascidian tunic protects the
      organism from UV radiation.

PMID- 14961394
TI  - Molecular cloning and characterization of two isoforms of trypsinogen from
      anchovy pyloric ceca.
AB  - Complementary DNA clones encoding two isoforms of trypsinogen were isolated from
      the pyloric ceca of anchovy by rapid amplification of cDNA ends (RACE).
      Nucleotide sequences of isolated clones encoded, in addition to characteristic
      signal and activation peptides, two isoforms of trypsin containing 220 and 221
      amino acid residues. Both enzymes contained the catalytic triad of a serine
      protease, together with the residues determining substrate specificity. The
      anchovy trypsins showed a high amino acid identity of about 80% to those of other
      fish species. Southern blot analysis with a probe cross-reactive to both isoforms
      showed a complex genomic pattern. Northern blot analysis with the same probe
      revealed the highest expression of messenger RNA in the pyloric ceca. Structural
      parameters possibly involved in higher catalytic properties of fish trypsin were
      examined by three-dimensional modeling, which included deletion in the autolysis
      loop, lack of Tyr-151 at the entrance of the S1 pocket, and distribution of
      charged residues.

PMID- 14961397
TI  - The UME-21 project: connecting medical education and medical practice.

PMID- 14961398
TI  - The Undergraduate Medical Education for the 21st Century (UME-21) project: the
      Federal Government perspective.
AB  - The Undergraduate Medical Education for the 21st Century (UME-21) project was
      implemented by the Division of Medicine, Bureau of Health Professions, Health
      Resources and Services Administration (HRSA) to encourage medical schools to
      collaborate with managed care organizations and others. The purpose of the
      collaboration was to ensure that medical students are prepared to provide quality
      patient care and manage that care in an integrated health care system in which
      the cost of care and use of empirically justified care are important elements.
      The UME-21 project represents a continuation of HRSA's interest in the managed
      care arena. The UME-21 project involved the collaboration of eight partner
      schools and 10 associate partner schools, together with 50 external partners, to
      develop innovative curricula that integrated UME-21 content from nine special
      areas as learning objectives. This project demonstrated that concerted efforts by
      the leadership in medical education can bring about innovative change in medical
      school curricula. It is also demonstrated that faculty of the three primary care
      disciplines of family medicine, general internal medicine, and general pediatrics
      were able to cooperate to accomplish such change by working together to allocate
      clerkship time and content. An important lesson learned in this project was that
      significant innovations in medical school curricula could be accomplished with a
      broadbased commitment and involvement of both faculties across the three primary
      care disciplines and top administrative officials of the medical school. It is
      uncertain, however, if the innovations achieved will produce further changes or
      if those changes achieved can be sustained without continued funding.

PMID- 14961399
TI  - Health care economics, financing, organization, and delivery.
AB  - BACKGROUND: The US health care system is in a state of rapid evolution, with
      changing payment, organizational, and management structures. To learn how to
      function optimally in a system in which care is increasingly managed and
      competitive, today's medical students must understand the structural and economic
      underpinnings of the system within which they will practice. At the outset of the
      Undergraduate Medical Education for the 21st Century (UME-21) project, the great
      majority of medical school curricula were lacking in areas of health care
      financing and organizational structure. The institutions involved in the UME-21
      project sought to address curricular deficiencies in two broad areas: (1) the
      structure and financing of the US health care system ("health policy") and (2)
      the manner in which this system is reflected in the organization and activities
      of health care providers ("care delivery"). This article discusses the
      development, implementation, and evaluation of the first of the two areas.
      METHODS: Data were abstracted from written reports provided by each of the UME-21
      schools to the project's Executive Committee and sponsor. In selected cases,
      additional data were obtained by personal communications with project directors
      and evaluators. Local UME-21 project leaders verified all data presented.
      RESULTS: Curricular philosophy and teaching methods varied widely, but health
      policy curricula were predominantly preclinical and didactic in nature. At the
      school level, much was achieved in terms of student knowledge, curricula were
      generally well received by students, attitudes toward managed care generally
      moved in a positive direction, and behavior may have been positively influenced
      as well. At the project level, many potentially interesting changes exist within
      the 18 schools and between the UME-21 and other schools, but it is not clear
      whether or what parts of the health policy curricula were responsible for these
      changes. Nonetheless, as measured by changes in health policy-related items on
      the Association of American Medical Colleges Graduation Questionnaire, it appears
      that UME-21 schools outperformed their non-UME-21 counterparts. All of the UME-21
      schools were enthusiastic about their health policy innovations, and this
      extended across all key stakeholders. Most schools avoided focusing on managed
      care and instead adopted more neutral themes that introduced the same material.
      Integrating the new material in conjunction with the more traditional aspects of
      the curriculum was also an effective implementation strategy. CONCLUSIONS: Health
      policy should be incorporated into both the preclinical and clinical years. The
      former emphasizes health care economics as one of the foundations of medical
      practice, whereas the latter provides the opportunity for its use on a daily
      basis in clinical settings. However, like any new curriculum, to achieve equal
      status with the traditional biomedical curriculum, it must be presented in a
      scholarly, rigorous, and reasonably comprehensive fashion. Mounting a scholarly
      health policy curriculum requires a wide-ranging, interdisciplinary faculty. If
      it is to become a central component of the medical school curriculum, creative
      approaches to faculty recruitment and development will be needed. This will
      require both careful educational policy formulation and new investment.

PMID- 14961400
TI  - Evidence-based and population-based medicine: national implementation under the
      UME-21 project.
AB  - BACKGROUND AND OBJECTIVES: The Undergraduate Medical Education for the 21st
      Century (UME-21) project developed and implemented innovations to medical school
      curricula at medical schools across the country. This report describes the
      development and implementation of innovative approaches to improving instruction
      in evidence-based medicine with a population-based perspective. METHODS: Each
      school participating in the UME-21 project designed, implemented, and evaluated
      its own unique curriculum initiatives. We examined these initiatives using data
      abstracted from written reports submitted to the project Executive Committee.
      Additional data were obtained by personal communication with project directors
      and evaluators at the various schools, student and preceptor comments, internal
      program evaluation at each school, and external evaluation by the UME-21 project
      leadership. The Association of American Medical Colleges Graduation Questionnaire
      was also used. RESULTS: Fourteen of 18 participating schools implemented a broad
      range of curricula to facilitate teaching and learning about evidence-based and
      population-based medicine. Common themes included the application of evidence to
      patient care, use of clinical practice guidelines and pathways, and the general
      incorporation of evidence-based techniques (literature searching, critical
      appraisal, etc) into the teaching of other content, such as clinical science and
      managed care. Teaching approaches included Web-based and other computer-based
      education, an emphasis on active and self-directed learning, use of small groups
      and workshops, and distribution of this content over multiple years. As an
      alternative to full-length evidence-based medicine courses, many schools
      incorporated an evidence-based approach into existing courses and clerkships.
      Data demonstrated an upward trend in student satisfaction with how topics were
      presented at UME-21 schools. CONCLUSIONS: These innovations successfully
      demonstrated that evidence-based and population-based medicine content can be
      introduced into medical school curricula. Introducing these constructs in ways
      that demonstrate their relevance to patient care facilitates student learning.

PMID- 14961401
TI  - UME-21 and teaching ethics: a step in the right direction.
AB  - BACKGROUND AND OBJECTIVES: Ethics education for medical students has included a
      number of relatively vague descriptions of appropriate curricular objectives, but
      medical schools struggle with the general teaching of ethics, as well as with
      presenting the ethical dilemmas posed by managed care. This paper proposes some
      standards and uses them to analyze the general and managed care ethics content of
      the Undergraduate Medical Education for the 21st Century (UME-21) curricula.
      METHODS: We analyzed progress and final reports from each school to define their
      learning objectives, content, teaching methods, and evaluation strategies in
      ethics. Each was evaluated using principles of adult learning and Rest's Four
      Component Model of Moral Development. Good examples of curricular elements from
      participating schools are described. RESULTS: Ethics curricula varied widely
      among the schools. Goals and objectives were often stated in generalities.
      Teaching methods were diverse and innovative, and several new combinations of
      learning activities were created to highlight ethics topics. Content represented
      managed care and non-managed care topics in varying proportions. Student surveys
      of attitudes toward managed care and opinions of the ethics programs were the
      most commonly used as evaluation tools. Some schools were able to develop more
      direct means of evaluating student learning. The Four Component Model was not
      fully addressed in the programs developed by the participating schools.
      CONCLUSIONS: We make recommendations about the objectives, teaching methods,
      content, and evaluation methods of an ideal medical school curriculum in ethics.

PMID- 14961402
TI  - Integrating the art and science of medical practice: innovations in teaching
      medical communication skills.
AB  - BACKGROUND AND OBJECTIVES: This paper describes the content and methods used to
      teach communication skills in Undergraduate Medical Education for the 21st
      Century (UME-21) schools and provides suggestions for future efforts. METHODS:
      Faculty leaders of curriculum projects at UME-21 schools provided reports
      describing new communication curriculum projects. Reports were reviewed and
      analyzed, curriculum content and methods were categorized into themes, and
      findings were confirmed through phone interviews with lead faculty at each
      participating school. RESULTS: Curriculum projects were designed to improve
      medical students' communication skills during the clerkship years at 12
      participating UME-21 schools. These skills were addressed through a variety of
      teaching methods and applied in interactions with patients, health teams, and
      community members. Curricular themes included conflict resolution, delivery of
      bad news, addressing patient preferences for end-of-life care, patient and
      community health education, communicating with families, and working effectively
      with patients from diverse backgrounds. Students' communication skill
      competencies were assessed through a variety of methods including objective
      structured clinical examinations, focused observation and feedback, and
      debriefing sessions based on recall, audiotapes, or videotapes of encounters.
      CONCLUSIONS: Opportunities for students to develop, apply, and refine their
      communication skills can be embedded throughout the medical school curricula. Our
      findings illustrate the variety of methods that may be used to teach and evaluate
      medical students' communication skill competencies. Future challenges include
      development of comprehensive longitudinal curricula, practical teaching methods,
      valid evaluation tools, and faculty development.

PMID- 14961403
TI  - Undergraduate medical education for the 21st century: leadership and teamwork.
AB  - BACKGROUND: The health care delivery system is experiencing enormous flux. The
      knowledge and skills sets required of today's physicians include expertise in
      competency areas that have not been included in the traditional medical
      curricula. The Undergraduate Medical Education for the 21st Century (UME-21)
      project was designed to develop innovative curricula that addressed the training
      necessary for medical students to gain skills required to provide high-quality,
      accessible, and affordable care in the modern health care environment. One of the
      nine UME-21 content areas, leadership and teamwork, has historically received
      relatively little attention in medical education. METHODS: Each school
      participating in the UME-21 project submitted a final report that provided
      information for this descriptive summary of curricular innovations for teaching
      the concepts of leadership and teamwork to medical students. A classification
      lexicon for the curricular content and experiences in this content area was
      derived from these UME-21 project reports. Each school evaluated its curricular
      innovations independently using a variety of methods, largely descriptive and
      qualitative in nature. RESULTS: Eight UME-21 schools developed curricula
      addressing the content area of leadership and teamwork. The majority of these
      curricula used the clinical care teams in the clinical rotations to demonstrate
      the principles and importance of leadership and teamwork. Three of the schools
      implemented didactic sessions and workshops to explicitly address leadership and
      teamwork. One school used the gross anatomy dissection teams as the "laboratory"
      for demonstrating this content material. The evaluations of these curricular
      efforts showed them to be positively regarded by the medical students. Outcomes
      of measurable changes in competency in this area of expertise were not evaluated.
      CONCLUSIONS: There is little past experience in teaching leadership and teamwork
      in medical school. The UME-21 project supported the design and implementation of
      several curricular innovations in this content area, which were well received by
      learners. These eight leadership and teamwork curricula are described, a lexicon
      outlining the specific content that was addressed in this content area is
      presented, and lessons learned are included in this report. Further efforts to
      demonstrate the mastery of new skills in this important content area, based on
      curricula such as these, are needed.

PMID- 14961404
TI  - Teaching quality measurement and improvement, cost-effectiveness, and patient
      satisfaction in undergraduate medical education: the UME-21 experience.
AB  - BACKGROUND: The health care system in the United States is changing at an ever
      increasing rate. Recent reports by the Institute of Medicine raising concerns
      regarding rates of medical errors and suggesting the need for reengineering of
      the health care delivery system have focused attention on the need for quality
      measurement and improvement. METHODS: We abstracted data from final written
      reports submitted by 18 Undergraduate Medical Education for the 21st Century (UME
      21) schools, as well as other materials available from participating UME-21
      schools. Specific curricular innovations developed and implemented were
      identified. Additionally, senior medical students' responses to the annual
      Graduation Questionnaire administered by the Association of American Medical
      Colleges (AAMC) were available for analysis. The change from 1999 to 2001 in the
      proportion of seniors rating instruction in quality assurance as adequate was
      compared among four groups of UME-21 schools and the other 107 US medical
      schools. RESULTS: Eleven of the 18 schools specifically addressed the content
      areas of quality measurement and improvement, including utilization management
      (27% of schools), cost-effectiveness (45% of schools), use of clinical practice
      guidelines (73% of schools), and patient satisfaction assessment (45% of
      schools). Each school developed unique approaches and educational materials
      pertinent to the content area. Overall, the percentage of seniors rating the
      relative amount of instructional time devoted to quality assurance in medicine by
      their school's curriculum as adequate or better rose from 49% to 66% between 1999
      and 2001 at the 11 UME-21 schools that introduced initiatives in quality
      improvement into their curricula. This change was significantly higher than the
      pattern at other US medical schools between 1999 and 2001, at which seniors'
      ratings rose only from 43% to 56%. CONCLUSIONS: Curriculum development and
      implementation addressing quality improvement in medical practice accelerate
      improvement of students' perception that their education has adequately addressed
      this subject area. This article summarizes some of the experiences, curricular
      approaches, successes, failures, and lessons learned in quality improvement by
      schools participating in the UME-21 project.

PMID- 14961405
TI  - Practicing effectively in today's health system: teaching systems-based care.
AB  - BACKGROUND AND OBJECTIVES: The Institute of Medicine and the new Accreditation
      Council for Graduate Medical Education General Essentials have focused attention
      on the Undergraduate Medical Education for the 21st Century (UME-21) core content
      area of systems-based care. Through teaching systems-based care, medical students
      can learn how physicians effectively deliver and coordinate care within the
      health system. While medical students can be introduced to the organization,
      financing, and delivery of the health care system through lectures, the
      principles and practice of systems-based care must be reinforced through
      structured learning experiences during the clinical (ie, third and fourth) years.
      The purpose of this article is to define the undergraduate clinical content and
      experiences in systems-based care offered by the eight UME-21 partner schools.
      METHODS: The eight partner UME-21 schools exposed third- and fourth-year medical
      students to a variety of clinical experiences outside the traditional teaching
      hospital in such settings as physician offices, skilled nursing facilities, the
      patient's home, hospice, and public health departments. They also taught systems
      based care skills such as care coordination, performance assessment, and quality
      improvement. RESULTS: Based on surveys of graduating students, the UME-21
      programs were successful in exposing students to the aforementioned topics,
      though there was variability among schools. DISCUSSION: The experiences of the
      UME-21 schools in teaching about systems-based care, as discussed in this paper,
      may be useful to those involved in medical school curricula planning.

PMID- 14961406
TI  - Teaching of medical informatics in UME-21 medical schools: best practices and
      useful resources.
AB  - OBJECTIVES: Information-based decision making is important to modern medical
      practice. This report identifies learning objectives, teaching innovations, and
      student outcomes for teaching medical informatics (MI) in medical schools that
      participated in the Undergraduate Medical Education for the 21st Century (UME-21)
      curriculum project. METHODS: Project reports by the UME-21 schools were analyzed,
      and curricular content was classified in terms of the five categories for MI
      literacy adapted from the Medical School Objectives Project. Student self
      assessments of adequacy of exposure to MI were reviewed. RESULTS: Teaching
      methods included demonstrations, lectures, small-group tutorials, hands-on labs,
      and task-based assignments. The curriculum was taught during the first 3 years of
      medical school with medical librarians participating. Content examples in the
      five categories of medical literacy were: "Role of the Lifelong Learner"
      (accessing, evaluating, and using information and databases), "Role of Clinician"
      (obtaining patient information, using decision support), "Role of
      Educator/Learner/Communicator" (accessing information for patient education,
      student-teacher communication, studying Web-based cases, making presentations,
      accessing on-line course information), "Role of Researcher/Evaluator"
      (documenting patient encounters), and "Role of Manager" (using drug formularies
      and clinical guidelines). Seniors exposed to the UME-21 curriculum reported
      higher levels of exposure to MI than did untrained seniors 2 years earlier;
      however, seniors at non-UME-21 schools reported equally high levels. CONCLUSIONS:
      UME-21 schools developed creative materials for teaching students to use
      computers for learning, communication, and searching for information. Outcome
      measures suggest that MI has become an important curriculum topic in most medical
      schools.

PMID- 14961407
TI  - Wellness and prevention.
AB  - BACKGROUND AND OBJECTIVES: The importance of wellness and prevention in medical
      education is well documented. This report discusses the educational innovations
      in wellness and prevention that were implemented as part of the Undergraduate
      Medical Education for the 21st Century (UME-21) project. METHODS: Eight partner
      schools and four of the 10 associate partner schools provided specific
      information about learning objectives, content, and methods used in incorporating
      wellness and prevention into the curriculum. Based on these reports, common
      learning objectives and core content were identified. RESULTS: Many schools
      emphasized that integration of content across courses and throughout the
      preclinical and clinical years was important in incorporating wellness and
      prevention content into existing curricula. A variety of instructional methods
      were used, including didactic lectures, workshops, smallgroup sessions, case
      studies, computer-based instructional modules, patient simulators, and
      standardized patient encounters. Based on partner reports, after completing the
      UME-21 project, students demonstrated gains in knowledge, clinical skills, and
      positive attitudes toward preventive care and wellness. The project outcome data
      indicated that student instruction in and exposure to preventive care was
      increased during the project. However, these increases were not significant when
      compared to their peers from non-UME-21 schools. CONCLUSIONS: Although partner
      schools used different methods to incorporate wellness and prevention, the UME-21
      project was an effective project in improving the educational experience in this
      content area for students from institutions that included this area in their
      educational innovations.

PMID- 14961408
TI  - Longitudinal small-group learning during the first clinical year.
AB  - BACKGROUND AND OBJECTIVES: Ethics education for medical students has included a
      number of relatively vague descriptions of appropriate curricular objectives, but
      medical schools struggle with the general teaching of ethics, as well as with
      presenting the ethical dilemmas posed by managed care. This paper proposes some
      standards and uses them to analyze the general and managed care ethics content of
      the Undergraduate Medical Education for the 21st Century (UME-21) curricula.
      METHODS: We analyzed progress and final reports from each school to define their
      learning objectives, content, teaching methods, and evaluation strategies in
      ethics. Each was evaluated using principles of adult learning and Rest's Four
      Component Model of Moral Development. Good examples of curricular elements from
      participating schools are described. RESULTS: Ethics curricula varied widely
      among the schools. Goals and objectives were often stated in generalities.
      Teaching methods were diverse and innovative, and several new combinations of
      learning activities were created to highlight ethics topics. Content represented
      managed care and non-managed care topics in varying proportions. Student surveys
      of attitudes toward managed care and opinions of the ethics programs were the
      most commonly used as evaluation tools. Some schools were able to develop more
      direct means of evaluating student learning. The Four Component Model was not
      fully addressed in the programs developed by the participating schools.
      CONCLUSIONS: We make recommendations about the objectives, teaching methods,
      content, and evaluation methods of an ideal medical school curriculum in ethics.

PMID- 14961409
TI  - Teaching the basics of clinical pharmaceutical care: innovative pharmacy
      workshops at the University of Wisconsin and the University of Nebraska.
AB  - BACKGROUND: Safe and effective prescription writing, using drug formularies, and
      managing pharmaceutical care are skills medical students need to acquire. Spurred
      by the Undergraduate Medical Education for the 21st Century (UME-21) grants, the
      University of Wisconsin and the University of Nebraska independently developed
      educational workshops to address these competencies. METHODS: The University of
      Wisconsin's workshop is presented to medical students at the start of their third
      year. They receive information from pharmacists on medication errors,
      prescription writing, and drug formularies. A "learners guide" summary is
      discussed by a physician, which brings into focus the clinical application of the
      didactic session. A small-group session follows with hands-on experience in
      writing prescriptions and using formularies for three patient case scenarios. The
      workshop at the University of Nebraska consists of three sessions during the
      third-year internal medicine clerkship. In the first session, pharmacists discuss
      formularies, the Pharmacy and Therapeutics (PT) committee, and the preparation of
      a drug monograph. During the second session, students develop an evidence-based
      drug monograph on a product or herbal. In the final session, the class functions
      as a mock PT committee, and after listening to the drug monographs, determines
      whether the product should be added to the formulary. We evaluated students'
      satisfaction with the workshops using Likert scales and assessed students'
      ability to correctly fill out a prescription form. RESULTS: Both workshops were
      well received. The mean rating at University of Wisconsin was 1.7 on a scale of 1
      (satisfied) to 7 (dissatisfied), and at University of Nebraska it was 3.8 with 5
      (outstanding) to 1 (unacceptable). At the University of Wisconsin, on a year-end
      skills assessment involving 148 students, 100% of the students properly filled
      out a prescription. Ninety-four percent received an excellent grade, 6% a pass,
      and no marginal or failing grades were given out. CONCLUSIONS: The workshop on
      pharmaceutical prescribing was rated favorably by students. After participating
      in the workshop, students acquired skills in prescription writing.

PMID- 14961410
TI  - From library to discharge: a managing care student project.
AB  - BACKGROUND AND OBJECTIVES: The Patient Care Project (PCP) was a central component
      of the Undergraduate Medical Education for the 21st Century (UME-21) grant
      project at the University of Nebraska. With the primary goal of improving
      students' critical thinking skills, the PCP was directed more toward an
      understanding of managing care than the business aspects of managed care and
      emphasized written communication skills, clinical hypothesis testing, and
      exploring ways to solve medical and ethical questions. METHODS: All 239 students
      graduating in 2000 and 2001 were required to analyze the medical care received by
      one of their hospitalized patients. Using a criterion-based evaluation tool,
      students' written critiques were assessed in five specific areas, all of which
      required critical thinking skills. Students also received an overall grade for
      the project. The UME-21 Graduation Survey was used to assess changes in attitudes
      and behavior. Students graduating in 1999, prior to the institution of the PCP
      graduation requirement, served as a control group. RESULTS: The most frequently
      discussed topic of the PCPs was cardiovascular disease. The mean overall rating
      by the faculty for the PCPs was 3.7 and 3.8 in academic years 2000 and 2001,
      respectively (maximum=5). In a qualitative analysis of the PCPs, students
      demonstrated insight into their patients' overall medical care, including the use
      of evidence-based medicine (EBM), quality improvement, and cost containment.
      There were no statistically significant differences, however, between the PCP and
      control groups on the UME-21 Graduation Survey. Nonetheless, more students who
      had completed the PCP reported that they had identified the total cost of a
      patient's stay, designed a quality improvement loop, and obtained clinical
      evidence from an EBM computer database. On this same survey, all students agreed
      with the use of clinical practice guidelines and cost containment. CONCLUSIONS:
      The PCP appeared to be relevant to the students' learning needs, and they
      provided cogent critiques of the medical care they had rendered as well as
      critical analyses of their patients' discharge summaries and the cost of care
      including ways to reduce cost. On the other hand, we were unable to demonstrate
      any substantial differences in the results of the UME-21 Graduation Survey given
      to both the PCP and control groups. In spite of this lack of effect on students'
      attitudes, the PCP was perceived by the faculty to be valuable and has been
      incorporated into the required third-year family medicine clerkship at the
      University of Nebraska.

PMID- 14961411
TI  - A curriculum in systems-based care: experiential learning changes in student
      knowledge and attitudes.
AB  - BACKGROUND: To provide efficient, quality patient care, physicians must have a
      fundamental understanding of how the health care delivery system functions and
      how to appropriately use the various components of this system. As part of the
      Undergraduate Medical Education for the 21st Century (UME-21) initiative, the
      University of Miami in partnership with AvMed Health Plans, a nonprofit managed
      care organization (MCO) developed a longitudinal educational program that
      prepares all students for medical practice in emerging systems of care. METHODS:
      The program, which spans the 4-year undergraduate curriculum, incorporates
      didactic sessions and practical experiences to teach about the clinical,
      managerial, financial, and ethical aspects of systems-based care. During the
      third year of medical school, students visit the administrative offices of AvMed
      Health Plans for a day-long series of presentation-discussions and experiential
      tours through the various administrative departments. There, they experience
      first-hand all facets of a systems-based approach to care using evidence-based
      practice guidelines, utilization review, quality measurement and improvement, and
      chronic disease management. RESULTS: An attitudinal survey, constructed to
      evaluate general attitudes toward managing care and MCOs, was administered to
      students at the beginning of their first, second, and third year and immediately
      before and after their visit to AvMed during their third year. Using factor
      analysis, there were no significant differences in students' attitudes at the
      beginning of the first, second, or third year nor immediately before the seminar
      day at the MCO. However, the day-long seminar at AvMed did have a favorable
      effect on attitudes toward systems of care and MCOs in general. In addition,
      students performed well on post-evaluation knowledge assessments addressing
      fundamental concepts of systems of care and the function of an MCO in managing
      the care of its members. The visit to the MCOs (AvMed) offices and the day-long
      curriculum was replicated at another medical school, with similar effects on
      students' attitudes. CONCLUSIONS: Medical students have neutral-to-negative
      opinions of systems of care and MCOs. Early educational experiences such as
      classroom lectures and panels that address managing care issues have minimal
      effect on these opinions. However, bringing medical students to an MCO's
      administrative offices, seeing first-hand how systems of care operate, and having
      an open dialogue with physician administrators does effect a positive change in
      medical student opinions of a system in which care is managed. In addition,
      medical students can gain new knowledge about effective systems-based practice.

PMID- 14961412
TI  - Promoting the development of doctoring competencies in clinical settings.
AB  - BACKGROUND AND OBJECTIVES: This UME-21 project was developed to promote a variety
      of clinical competencies during a 12-week medicine clerkship for third-year
      students. METHODS: The clerkship is divided into three 4-week rotations--two
      inpatient rotations and one outpatient rotation. During each rotation, students
      select a competency, review the module about that competency on the clerkship Web
      site, and perform a literature search. Learning exercises prompt students to ask
      their preceptor to model and discuss the performance of the competency on at
      least one patient and to provide feedback on their performance at least twice. At
      the end of each rotation, students are required to write about what they learned
      from the articles they read, write a critical analysis of their performance of
      the competency on one patient, and complete an evaluation questionnaire. This
      report is based on the results from the students' evaluation questionnaire.
      RESULTS: At the end of the first six rotations, 120 students completed 330
      evaluations of the course (93% response rate). The most frequently selected
      competency modules were behavior modification and patient education. In 81.5% of
      the evaluations, students felt that there was at least moderate improvement in
      their ability to perform the selected competency during the rotation. By the end
      of the rotation, in 85.3% of the evaluations, students indicated that they were
      confident performing the competency most or almost all of the time. Observing the
      preceptor was the component of the curriculum most often rated as helpful
      (59.1%), followed by literature review (57.9%), reviewing the Web site module
      (45.2%), and observation and feedback by the preceptor (32.7%). CONCLUSIONS:
      Based on student reports, the approach described in this paper appears to be a
      promising way to teach important doctoring competencies in a clinical setting.

PMID- 14961413
TI  - A weekend program model for faculty development with primary care physicians.
AB  - BACKGROUND: Medical teachers are expected to be proficient at teaching students
      and residents about the changing health care system. The University of Wisconsin
      established a faculty development fellowship program to better prepare clinical
      teachers in family medicine, general pediatrics, and general internal medicine.
      This paper describes our fellowship program, presents data on program
      accomplishments, and discusses what we have learned. METHODS: We developed a year
      long series of five weekend workshops. A core group of faculty provided 2- to 4-
      hour sessions on topics including evidence-based medicine, physician leadership,
      advocacy, doctor-patient communication, quality, technology tools, and teaching
      skills. Evaluation data were used to shape the program, make improvements, and
      assess impact. Fellows self-assessed their ability to perform skills at the
      beginning and ending of the year; paired t tests were used to compare these
      changes. RESULTS: Attendance and program completion rates were more than 94% for
      the 84 fellows taught over 6 years. Individual sessions and the overall program
      were well-rated by fellows. Participants reported improvements in targeted
      skills; statistical analyses confirmed many significant pre-post improvements.
      LESSONS LEARNED: To obtain high ratings, faculty must apply adult learning and
      active learning principles; lectures were not well tolerated. Initial technology
      skills were often low; computer labs needed many helpers. Participants needed
      extensive faculty support on their projects. It facilitated coordination and
      learning to have a core group of fellowship faculty who did most of the teaching.
      Graduates have become enthusiastic recruiters for new fellows. Our 5-weekend
      program has proven to be an effective faculty development model.

PMID- 14961414
TI  - Preparing faculty to teach managing care competencies: lessons learned from a
      national faculty development program.
AB  - BACKGROUND: Although competencies for managing care are often described in the
      medical literature, educators have been slow to integrate these competencies into
      clinical curricula. Backlash against managed care has created a skeptical
      educational environment. Many faculty feel unprepared to teach the competencies
      in clinical settings. METHODS: From 1999 to 2001, we designed, implemented, and
      evaluated a faculty development program, funded by the Bureau of Health
      Professions, Division of Medicine. The goal of the program was to increase
      Undergraduate Medical Education for the 21st Century (UME-21) and Partnerships
      for Quality Education (PQE) faculty skills in teaching quality improvement and
      costeffectiveness in the clinical setting and to prepare them to teach these
      topics to other faculty. RESULTS: Thirty-nine faculty attended the 4-month
      faculty development program. The program, in a train-the-trainer model, consisted
      of two 2-day workshops as well as pre-, mid-, and end-program activities and
      teaching experiences. Readings, brief lectures followed by focused discussion,
      and active learning experiences were used to teach content, provide experience
      and feedback with teaching skills, and model a variety of teaching approaches.
      CONCLUSIONS: By the end of the program, participants believed that they had
      learned content (knowledge) and gained practical teaching skills. To be
      successful in effecting curriculum change around new topics, such as the managing
      care competencies, faculty need to not only master new content and methods but
      also learn how to be change agents in their schools. Because this work can be
      lonely, faculty need support within the school and connections with others,
      locally and nationally, who have similar ideas.

PMID- 14961415
TI  - Partnerships between health care organizations and medical schools in a rapidly
      changing environment: a view from the delivery system.
AB  - BACKGROUND AND OBJECTIVES: The Undergraduate Medical Education for the 21st
      Century (UME-21) project encouraged the formation or enhancement of partnerships
      between medical schools and health care organizations distinct from the
      traditional teaching hospitals. The purpose was to prepare medical students in
      nine content areas that were components of the UME-21 project. Despite their
      importance today to medical schools, such partnerships with health care
      organizations are a challenge to develop and maintain in the midst of a rapidly
      changing health care environment. This article categorizes the partnerships
      formed and discusses the benefits and the barriers encountered in such
      collaborations. METHODS: Information about the partnerships was abstracted from
      written reports from each of the UME-21 partner schools. Additional information
      was obtained from personal communications with external project representatives
      and from a post-project survey presented to all UME-21 partner schools. RESULTS:
      The eight partner schools established or enhanced 32 educational partnerships
      with external organizations. External partner organizations contributed to
      curriculum planning and implementation, course development and presentation, and
      provision of clinical sites and preceptors. Twenty-seven of 32 initial
      affiliations continued in some form beyond the contract period. CONCLUSIONS:
      Partnerships formed as part of the UME-21 project improved medical students'
      exposure to the health care system and their knowledge and skills for effective
      practice in the 21st century health system. Barriers encountered included
      financial pressures, changes in leadership, different organizational missions and
      priorities, and preexisting prejudices against new relationships. Factors
      associated with successful partnerships include the presence of a health care
      organization and an academic "champion" dedicated to the project, strong
      individual relationships, and a medical school commitment to involve external
      partners.

PMID- 14961416
TI  - Collaborating to integrate curriculum in primary care medical education:
      successes and challenges from three US medical schools.
AB  - BACKGROUND AND OBJECTIVES: Traditional medical school department-based clerkship
      structures can lead to redundancy and/or gaps in curriculum, inefficient
      administrative systems, and academic isolation for clerkship directors. This
      paper describes the approaches, successes, and challenges three institutions
      experienced when implementing an interdepartmental collaboration to create an
      integrated primary care clerkship experience. METHODS: Each school combined
      family medicine, ambulatory pediatrics, and ambulatory medicine into contiguous
      clerkship blocks. In all institutions, each clerkship maintained certain distinct
      features while the integrated aspects contained longitudinal curriculum of
      certain primary care topics. RESULTS: Evaluations by students demonstrated
      favorable responses to the new content and integrated methods of teaching, as did
      results of the Association of American Medical Colleges graduation survey.
      Faculty at each institution reported that their multidisciplinary approach has
      stimulated important educational collaborations, many of which require an economy
      of scale not often achievable within a single clerkship. These included
      innovative evaluation/documentation efforts; centralization of administrative
      tasks; enhanced recruitment, retention, and development of community-based
      faculty; an increase in the active core group of local and national primary care
      leaders; and an increase in scholarly activities. The collaborations have not
      occurred without challenges, primarily in the need for identifying sustainable
      resources for these and future collaborative educational endeavors. CONCLUSIONS:
      The benefits involved in developing an integrated primary care experience include
      expansion of curriculum content and methods, as well as enhancement of collegial
      support and resources to community-based and academic faculty. These integrations
      do, however, bring added challenges, time, and costs to traditional independent
      clerkships.

PMID- 14961417
TI  - UME-21 local evaluation initiatives: contributions and challenges.
AB  - BACKGROUND AND OBJECTIVES: The 18 medical schools involved in the UME-21
      initiative developed innovative curricula and evaluation strategies. While there
      was significant variation in how schools approached the evaluation process, there
      were common methodological issues and challenges affecting the reliability of
      scores and validity of interpretations regarding outcomes. This paper explores
      these issues and challenges, using experiences from selected UME-21 schools.
      METHODS: Four evaluation issues and strategies are discussed: instrument
      development, study design, process evaluation using formative evaluation methods,
      and qualitative strategies. Within each discussion, examples from a UME-21 school
      are presented. RESULTS: The four evaluation strategies offered the flexibility to
      match local evaluation needs with an effective approach to evaluations.
      CONCLUSIONS/IMPLICATIONS: The school-level evaluation requirements by the UME-21
      initiative provided schools the flexibility to design individualized evaluation
      strategies, yet also encouraged collaboration among evaluators. While this
      strategy resulted in many successes at the school level, it also served to
      identify common methodological challenges that can be used as a guide for other
      schools in implementing and evaluating curricula.

PMID- 14961418
TI  - Evaluation of the UME-21 initiative at 18 medical schools between 1999 and 2001.
AB  - BACKGROUND: This study evaluated the processes of curricular change and the
      initial outcomes of the Undergraduate Medical Education for the 21st Century (UME
      21) project at 18 schools. METHODS: Site visits were conducted at eight partner
      schools in 1999 and 2001. Written proposals, progress reports, and final reports
      of 18 schools were reviewed. Senior medical students' responses to
      questionnaires, including the annual Association of American Medical Colleges
      Graduation Questionnaire and a UME-21 supplemental graduation questionnaire, were
      analyzed. RESULTS: There was variation among the schools in the curriculum at
      baseline, in the structure of the UME-21 innovation that was introduced, and in
      the process of implementation. There was an increase in seniors' ratings of
      instruction in the newer areas of evidencebased medicine, quality assurance, and
      cost-effectiveness in relation to national norms between 1999 and 2001. There was
      less impact on the more traditional content areas of ethics, patient
      communications, prevention, and leadership skills. CONCLUSIONS: The circumstances
      of the national evaluation introduced many methodological complexities, some of
      which could have been avoided if planning for evaluation had started earlier.
      However, the evaluation revealed that even modest funding directed toward
      specific curricular goals can produce measurable change and can have effects that
      extend beyond the initial scope of the project.

PMID- 14961419
TI  - Lessons learned-UME-21 project.
AB  - The Undergraduate Medical Education for the 21st Century (UME-21) project evolved
      from two prior projects that were aimed at studying the interface between managed
      care and undergraduate medical education. The project provided funding for 18 US
      medical schools to demonstrate how they would produce graduates who eventually
      could practice in a rapidly changing health care environment. Medical schools
      were required to provide educational opportunities in nine content areas or
      outline why such educational opportunities could not be provided in their
      individual projects. Participating schools were chosen via an involved process
      after careful evaluation by a panel of experienced medical educators. In a
      project of this type, many lessons are learned. In the UME-21 project, lessons
      learned were gleaned from progress reports, participant annual reports,
      proceedings from annual project meetings and a National Symposium, findings of a
      National Education Group, and published papers. A lesson must have been reported
      by a least two involved schools to be included. The lessons learned were divided
      into six categories as follows: content areas, implementation, collaboration,
      evaluation, governance, implications- summary. Many lessons emanated from each of
      these categories; however, only the 10 most important lessons in each category
      are presented. The implications of the lessons learned are outlined and provide
      direction for the future of medical education innovation and research.

PMID- 14961420
TI  - Ultrasound in Europe.

PMID- 14961421
TI  - [Non-invasive assessment of coronary flow reserve - valuable functional
      information in cardiac workflow].
AB  - Coronary flow reserve can be determined echocardiographically in the LAD in about
      90 % and in the RCA in more than 80 % of patients respectively by the use of
      modern high-resolution ultrasound equipment. For this purpose either high
      frequency fundamental imaging or echo-contrast enhanced harmonic Doppler
      technology is used. The main advantage of the method lies in its noninvasiveness
      and the lack of radiation exposure. In combination with coronary morphologic
      findings obtained from heart catheterization, CFR is helpful in the planning of
      further invasive procedures for coronary artery disease and in the estimation of
      the prognosis of such procedures. The functional status after PTCA of LAD/RCA or
      mammary bypass surgery can be evaluated during follow-up monitoring. Alteration
      in the coronary microcirculation can also be discovered in a non-invasive way,
      improvement of microcirculatory disorders by adequate therapy can be assessed by
      serial measurements of CFR.

PMID- 14961422
TI  - Abnormal regulation of maternal cerebral blood flow under conditions of
      gestational diabetes mellitus.
AB  - AIM: Gestational diabetes mellitus is a prediabetic state leading to endothelial
      dysfunction and altered organ perfusion. Under normal conditions cerebral blood
      flow is closely coupled to cortical activity, to which it rapidly adjusts. On the
      basis of this so-called neurovascular coupling we evaluated the influence of a
      gestational diabetic state on endothelium-dependent vasoregulative properties of
      this mechanism. METHOD: A functional transcranial Doppler test performed during
      visual stimulation was used to measure vascular reactivity. Peak systolic and end
      diastolic flow velocity response from 20 non-pregnant (age 27 +/- 6 y), 31
      healthy pregnant women (31 +/- 6 y; 31 +/- 4 gestational week) and 30 women with
      gestational diabetes (32 +/- 5 y; 34 +/- 4) were separately evaluated according
      to a control system approach. All women did not show any vascular risk factors
      prior to pregnancy. RESULTS: Comparison of resting blood flow velocity and the
      control system parameters of gain, attenuation, rate time and natural frequency,
      showed a consistent and significant difference in the parameter "attenuation" for
      the peak systolic data (0.55 +/- 0.18 vs. 0.44 +/- 0.1 and 0.45 +/- 0.11, p <
      0.01) as well as end-diastolic (0.61 +/- 0.23 vs. 0.49 +/- 0.2 and 0.5 +/- 0.14,
      p < 0.05) figures (mean +/- SD of value from women with gestational diabetes vs.
      non-pregnant and healthy pregnant women, significance level). No differences were
      found between non-pregnant and normal pregnant women for the neurovascular
      coupling mechanism. CONCLUSIONS: Gestational diabetes mellitus results in
      endothelial dysfunction which can be measured in a non-invasive, painless and
      easy manner by a transcranial Doppler test.

PMID- 14961423
TI  - [Value of sonography after rotator cuff repair: a comparison with MRI and
      clinical results].
AB  - AIM: How well do ultrasound- and MRI-results after rotator cuff reconstruction
      correlate with postoperative clinical findings? METHODS: Ultrasound- and MR
      imaging of the afflicted shoulder on 40 patients who were surgically managed for
      isolated tear of the tendon of supraspinatus was performed at least 24 months
      after intervention. Patients were also clinically assessed. Based on the clinical
      result, sensitivity and specificity for the two imaging procedures was
      determined. RESULTS: Only 11 (27.5%) patients had a completely inconspicuous
      ultrasonography. By ignoring the sonographic parameter "echogenicity" this number
      was raised to 29 (72.5%) patients. Without the above mentioned parameter
      ultrasonography demonstrated a good specificity (90.3%) yet a poor sensitivity
      (33.3%). Incorporation of "echogenicity" markedly weakened both values. MR
      imaging showed an intact cuff in 32 (80%) patients, 5 (12.5%) had signs for a
      partial tear and in 3 (7.5%) a recurrent tear was diagnosed. Based on the
      clinical result, MR-imaging showed sufficient specificity (87.1%), yet also a
      poor sensitivity (44.4%). CONCLUSION: After rotator cuff repair MRI- and
      ultrasound-findings frequently stand in distinct discrepancy to clinical results.
      Based on clinical findings, postoperative MR-imaging shows a slightly higher
      sensitivity than ultrasonography. Despite this, both radiographic methods do not
      allow deductions concerning the clinical outcome. The postoperative shoulder-scan
      and MRI should therefore be interpreted with utmost care. Symptoms and functional
      results are of high clinical relevance in the assessment of the postoperative
      shoulder.

PMID- 14961424
TI  - Ultrasound of the breast - value of sonographic criteria for the differential
      diagnosis of solid lesions.
AB  - OBJECTIVE: The investigation of the value of sonographic criteria for the
      assessment of the character of solid breast lesions. METHODS: 281 preoperative
      sonographic studies of breast lesions were analysed and classified according to
      the following features: characteristics of the contour, echodensity, echo
      pattern, posterior acoustic properties, mobility, compressibility, axis of the
      lesion, L/T ratio (longitudinal size divided by transverse size), and
      architecture of surrounding tissue. We assessed the differential diagnostic value
      of each feature based on frequency distribution and odds ratio (OR). RESULTS: 152
      (54.1 %) benign and 129 (45.9 %) malignant breast lesions were evaluated by
      ultrasound. The following sonographic criteria were the most clear-cut signs for
      lesions to be malignant: ill-defined borders (OR: 19.8), incompressibility (OR:
      9.7), and discontinuity of Cooper's ligaments (OR: 4.8). Benign lesions were
      characterised by compressibility (OR: 0.12), smooth borders (OR: 0.12), and
      displacement of Cooper's ligaments (OR: 0.24). CONCLUSION: When distinguishing
      benign from malignant breast lesions, ultrasound examiners should be primarily
      guided by the lesion's contour and compressibility and the architecture of the
      surrounding tissue. Aiming for the widest possible consensus on terminology
      issues and standardised interpretation of the above criteria would help to
      advance breast sonography from its current status as a supplementary technique to
      the status of the modality of choice for the early diagnosis of breast cancer.

PMID- 14961425
TI  - [Perineal sonography: using time modulated 2D-ultrasound in a freehand 3D
      technique].
AB  - AIM: The employment of a new transperineal ultrasound technique, which
      demonstrates the dynamics of the temporal change in the positions of the urethra
      and bladder under standardized Valsalva pressure, was evaluated with regards to
      the possibility of diagnosing and classifying the various types of descension.
      METHOD: Transperineal ultrasound using a 3 - 5 MHz Curved array transducer was
      performed on 21 female patients with urinary incontinence. The results were
      compared with the clinical examinations and the urodynamic measurements. RESULTS:
      17 of 21 profiles could be clearly classified as either rotatory or vertical
      descension types. 2 of the profiles could not be classified due to lack of
      patient cooperation, and 2 could not be classified due to technical problems.
      CONCLUSION: This new method allows a safe diagnosis of the descension types in
      most cases. All dynamics of the examination can be documented.

PMID- 14961426
TI  - New nomogram for foetal weight estimation based on Hadlock's two-parameter
      formula.
AB  - AIM: To develop and validate a graphical method for ultrasonic foetal weight
      estimation with predictive qualities comparable to state-of-the-art computational
      methods. METHOD: Study data were obtained from 3839 consecutive singleton
      pregnancies with ultrasound examination within 7 days of delivery. We translated
      the well established Hadlock 2-parameter formula based on abdomen circumference
      and femur length into a nomogram [corrected]. We compared the measured foetal
      weight with estimations obtained from this new nomogram and three other methods.
      RESULTS: Measured by the foetal weight percentage error the new nomogram
      underestimates the foetal weight on average by 2.5 % (9.86) (mean [SD]) with
      uniform results over the complete birth weight spectrum. By the same measurement
      the Hadlock 4-parameter formula underestimates the foetal weight by 1.2 % (9.3)
      whereas the Hansmann nomogram overestimates the foetal weight by 14.5 % (16.1)
      The difference between the estimated foetal weight percentage error obtained from
      the new nomogram and from the Hadlock 2-parameter formula is 0.06 % (0.27) and
      hence clinically irrelevant. CONCLUSION: The new nomogram has predictive
      qualities comparable to state-of-the-art computational methods and is thus not
      only as reliable but also easy to use in situations when computers are not
      available. It can be recommended for foetal weight estimation over the whole
      spectrum of birth weight.

PMID- 14961427
TI  - Malignant lymphoma accompanied by renal cell carcinoma - a not so rare
      coincidence?
AB  - We report a case of a patient who presented with a left sided inguinal swelling.
      Ultrasound examination clearly revealed a bilateral inguinal lymphoma. In
      addition, a renal cell carcinoma was diagnosed through ultrasound. The
      differences in texture between lymph nodes and renal tumour as well as the even
      concentric swelling of the lymph node sinus permitted a clear cut differentiation
      between the two entities. CT could not provide this clear distinction. Despite
      some controversy several case reports as well as a few retrospective studies
      showed an increased coincidence of renal cell carcinoma and malignant lymphoma.
      However, a pathophysiological connection has not yet been discovered. This report
      presents another case of synchronous appearance of renal cell carcinoma and
      malignant lymphoma and demonstrate the relevance of ultrasound in the
      discrimination between the two clinical entities. It is essential for physicians
      performing either sonography and/or CT to be aware of this coincidence to avoid
      misdiagnosis of lymphadenopathy in patients with renal cell carcinoma as
      metastasis and, vice versa, renal tumours in lymphoma patients as renal
      manifestation of the lymphoma.

PMID- 14961428
TI  - Lemierre's syndrome: the forgotten disease. An unusual presentation of sepsis.
AB  - A 19-year-old girl presented with a septical condition with fever of 40 degrees
      C, swelling of the right sternocleidomastoid region and abdominal pain. Except
      for a sore throat with pain strictly localized to the right side of her neck and
      fever over the last week there were no other clues in her past medical history.
      An abdominal ultrasound and MRT scan as well as a chest X-ray only showed non
      specific findings. The diagnosis of Lemierre's syndrome was established by
      ultrasonographical detection of right jugular venous thrombosis and perivascular
      inflammation together with blood cultures positive for Fusobacteria. The patient
      recovered within days after treatment was initiated with metronidazol according
      to the antibiogram. Lemierre's syndrome is a life-threatening disease especially
      in an age group which is less frequently affected by septicaemia. A history of
      sore throat, Fusobacterium positive blood cultures and ultrasonographical
      detection of jugular venous thrombophlebitis together with the knowledge of the
      "forgotten disease" will lead the way to the diagnosis.

PMID- 14961429
TI  - [About quality of diagnostic ultrasound - an enduring problem between reality and
      satire].

PMID- 14961430
TI  - [Observational studies on ultrasound screening for developmental dysplasia of the
      hip in newborns - a systematic review?].

PMID- 14961431
TI  - [Global strategy for chronic obstructive pulmonary disease (GOLD). Update for the
      GOLD recommendations].

PMID- 14961432
TI  - [Transplantation of the lung - prolonged survival].

PMID- 14961433
TI  - [Compensation of low profusion coalworkers' pneumoconiosis. New occupational
      disease, new convention or leave it as it is?].

PMID- 14961434
TI  - [Quality of life and exercise capacity in lung transplant recipients].
AB  - BACKGROUND: Quality of life in lung transplant recipients (LTR) is reported to be
      comparable with that of the general population. However, previous studies have
      shown that exercise capacity was reduced to 30 - 40 % of normal values. The
      purpose of this study was to investigate the gap between good self-reported
      quality of life and reduced exercise capacity in LTR, to describe possible
      correlations and to compare the results with those of a control group (CG).
      METHODS: 27 LTR 208 +/- 67 days after bilateral lund transplantation (16 male, 11
      female; age: 46 +/- 10 years; body mass index: 24 +/- 3 kg x m (- 2), FEV (1) %
      75 +/- 27 %) and 30 controls (17 male 13 female; age 47 +/- 15 years; BMI: 26 +/-
      4 kg x m (- 2), FEV (1) % 103 +/- 15 %) performed cardiopulmonary exercise
      testing and were interviewed with the standardized German "Quality of life
      profile for chronic disease" self-rating questionnaire. RESULTS: Significant
      differences were shown in objective exercise related variables (peak oxygen
      consumption: LTR 15.1 +/- 1.8, CG 34.5 +/- 9.1 ml x min (- 1) x kg (- 1); p <
      0,01); peak workload: LTR 1.0 +/- 0.2; CG 2.4 +/- 1.0 W. kg (- 1); p < 0.01);
      percentage of predicted workload: LTR 44 +/- 12, CG 115 +/- 33 %; p < 0.01). The
      rating of subjective quality of life in physical, psychological and social
      domains of LTR did not differ from values of the CG or of the general population
      (n = 1143). The quality of life in the physical domain correlated significantly
      with peak exercise capacity (LTR r = 0.44, p < 0.05; CG r = 0.37; p < 0.05).
      CONCLUSION: Patients 7 months after lung transplantation described their
      physical, social and psychological quality of life as equally good as the healthy
      control group. However, peak exercise capacity and oxygen consumption were
      markedly reduced. To improve physical capacity in the range of daily activities,
      an exercise training program should be offered to patients after lung
      transplantation.

PMID- 14961436
TI  - [Surgical treatment of pulmonary aspergilloma].

PMID- 14961437
TI  - [Parapneumonic effusion and pleural empyema - topical aspects of classification,
      diagnosis and treatment].
AB  - Parapneumonic effusions can be diagnosed in about 40 - 50 % of patients with
      bacterial pneumonia, and therefore should be considered as a frequent condition.
      Despite their prevalence, there is limited consensus about diagnostic pathways
      and therapeutic procedures due to the lack of evidence-based data available. The
      classification of parapneumonic effusions is based on morphological, chemical and
      bacteriological criteria. Dependent on the complexity of the effusion, available
      management approaches include observation without intervention, thoracentesis,
      chest tube drainage with or without local fibrinolysis and the surgical options
      VATS and thoracotomy. This overview summarizes the actual aspects of
      classification, diagnosis and treatment of the parapneumonic effusion and draws
      conclusions for the daily management of this condition.

PMID- 14961438
TI  - [Recommendations for personal respiratory protection in tuberculosis].
AB  - These recommendations of the German Central Committee against Tuberculosis give
      an overview of the current scientific knowledge on the tuberculosis risk of
      health service employees and on the risk of infection in individual areas of
      work. The efficacy of face masks and their benefit in tuberculosis control is
      discussed. There are no reliable data on the efficacy of face masks in preventing
      infection with M. tuberculosis, nor can such data be expected in the near future,
      due to the complex interaction of infection-preventing measures. As rapid case
      finding, isolation, and immediate, effective treatment of infected patients
      already greatly diminish the risk of transmission, we consider face masks to be
      of limited use in reducing this risk. However, they may be beneficial in certain
      areas of work and in certain situations, particularly in the presence of elevated
      aerosol concentrations. The benefit of face masks depends largely on their
      correct application. The choice of a particular type of mask requires knowledge
      of the current epidemiological situation, and a competent assessment of the risk
      in the area of work for which it is chosen, taking into account the closeness of
      contact with potentially infectious tuberculosis patients.

PMID- 14961439
TI  - [Occupational allergies to xylanases].
AB  - The exposure against enzyme dusts have long been known to cause occupational
      allergies. In the 1960s an increasing number of occupational allergies in the
      detergent industry were observed. In this context the high sensitization
      potential of enzyme dusts attracted attention. The present evaluation of
      literature data confirms that this is also true for xylanases. These frequently
      used industrial enzymes belong to the hemicellulases and are mostly of fungal
      origin. Several cases of specific airway sensitization caused by xylanases or
      other hemicellulases are verified by a number of case reports and cross sectional
      studies. As symptoms, results of skin prick tests, detection of specific IgE
      antibodies and results of specific bronchoprovocation tests are consistent, an
      immunologic mechanism can be assumed.

PMID- 14961442
TI  - [Advances in oncology--pathogenesis and individualized therapy].

PMID- 14961440
TI  - [Effects on the lung due to underground coal mining work].
AB  - The long-term exposure to dust in the hard coal mining industry can lead to
      various pathological lung changes, especially to chronic bronchitis without and
      with obstructive ventilation disorder, lung emphysema, pneumoconiosis (coal
      miner's pneumoconiosis, in Germany categorized as silicosis) and
      silicotuberculosis. These health disorders show a close pathogenetic and
      pathophysiological association and should not necessarily be regarded as
      individual entities. Most exposed subjects demonstrate more or less all of these
      pathological disorders. On account of individual (genetic?) susceptibility, their
      degree differs greatly. Some individuals are largely resistent, other subjects
      show severe effects like emphysema, progressive massive pneumoconiosis, or the
      Caplan syndrome. Several studies showed that the pathologically verified degree
      of lung fibrosis is associated with lung crystalline SiO(2) content whereas the
      emphysema score is inversely correlated with the coal content. With regard to
      diagnostics and medical expert opinion, it is important that conventional
      radiology has a low sensitivity. Further, health impairments of miners engaged
      for longtime which are insurance relevant (MdE) exist in cases without (BK 4111
      if beginning after 12/31/1992) or with coalworkers' pneumoconiosis even for
      categories < 2/3.

PMID- 14961443
TI  - [Acute upper gastrointestinal bleeding as initial manifestation of a
      gastrointestinal stromal tumor].
AB  - HISTORY: An 80-years-old man was admitted to our clinic because of upper
      gastrointestinal bleeding with tarry stool for 3 days after taking non steroidal
      antiinflammatory drugs (NSAID) for back pain. The history was otherwise
      unremarkable. INVESTIGATIONS: Laboratory results showed anaemia. Initial
      endoscopy revealed acute bleeding from an elevated ulcer in the pars inferior of
      the duodenum. The bleeding was successfully treated by epinephrine and fibrin
      injection. Biopsies showed inflammatory changes without presence of malignant
      cells. In the CT scan of the abdomen there was a mass near the ligament of Treitz
      of 6.3 cm in diameter adjacent to the duodenum. CLINICAL COURSE: The abdominal
      tumor was not suitable for ultrasound-guided biopsy. Therefore, laparotomy and
      surgical resection of the tumor were performed. Histology showed a
      gastrointestinal stromal tumor (GIST) with infiltration of the muscle layer of
      the duodenal wall with one small local metastasis. No lymph node metastases were
      present. The tumor was surgically completely removed and the regular follow-up
      examinations have fo far shown no evidence for tumor recurrence or metastases.
      CONCLUSIONS: In upper gastrointestinal bleeding from unusual sites, GIST has to
      be considered as an underlying disease even if endoscopic biopsies are negative
      for neoplastic changes.

PMID- 14961444
TI  - [A huge malignant degenerating neurofibroma of the lower leg coexistent with type
      1 Recklinghausen disease].
AB  - HISTORY: A 65-year-old man had noted a tumor of the right lower leg that had
      progressively grown over the last twenty years. He had a dyspnoea on
      insignificant movement and was relatively immobile because of the extent of the
      tumor. The tumor had been diagnosed as a Klippel-Trenaunay syndrome.
      INVESTIGATIONS: Laboratory investigations suggested a hypochromic and microcytic
      anaemia and an inflammatory constellation. The tumor had no av-fistulas on
      ultrasonography and angiography, but there were many pathological arteries and
      tumor nodes. The tumor nodes had been seen also on MRI-biopsy suggested a
      neurogenic sarcoma. DIAGNOSIS AND TREATMENT: Amputation of the leg was necessary.
      The histological diagnosis was neurofibrosarcoma with extensive necrotic areas
      and Recklinghausen disease. Investigation did not reveal any metastasis.
      Postoperatively the anaemia regressed and the patient learned to walk with a
      prosthesis. CONCLUSIONS: This history shows the problem of separating clearly the
      two hereditary diseases. Often there is a different clinical picture in everyday
      life. One must consider the definitely higher risk of malignant tumors of
      patients with neurofibromatosis. Ultrasonography is a non-invasive method that
      can provide morphological information on soft parts and pathology of the vessels.
      It facilitates the classification of such.

PMID- 14961445
TI  - [Diagnosis and treatment of hepatocellular carcinoma].

PMID- 14961446
TI  - [Advances in the treatment of ovarian carcinoma].

PMID- 14961447
TI  - [Sentinel node biopsy in breast cancer. German Society for Senology defines
      quality standards].

PMID- 14961448
TI  - [Proteases in malignant tumors. Their significance for pathogenesis and possible
      therapeutic consequences].

PMID- 14961449
TI  - [Current questions on off-label-use].

PMID- 14961451
TI  - Oculocutaneous albinism type 4 is one of the most common types of albinism in
      Japan.
AB  - Oculocutaneous albinism (OCA) is a complex genetic disease with great clinical
      heterogeneity. Four different types of OCA have been reported to date (OCA1,
      OCA2, OCA3, and OCA4). MATP was recently reported in a single Turkish OCA patient
      as the fourth pathological gene, but no other patients with OCA4 have been
      reported. Here, we report the mutational profile of OCA4, determined by genetic
      analysis of the MATP gene in a large Japanese population with OCA. Of 75
      unrelated patients that were screened, 18 individuals (24%) were identified as
      having OCA4; they harbored seven novel mutations, including four missense
      mutations (P58S, D157N, G188V, and V507L) and three frameshift mutations
      (S90CGGCCA-->GC, V144insAAGT, and V469delG), showing that MATP is the most
      frequent locus for tyrosinase-positive OCA in Japanese patients. We discuss the
      functional melanogenic activity of each mutant allele, judging from the
      relationship between the phenotypes and genotypes of the patients. This is the
      first report on a large group of patients with OCA4.

PMID- 14961452
TI  - Epidemiology of coronary heart disease in women.
AB  - Cardiovascular disease (CVD) is the leading cause of mortality in women and a
      major cause of morbidity. Coronary heart disease (CHD) accounts for nearly half
      of all CVD deaths. Gender differences in CHD include a later age of onset for
      women, a greater prevalence of comorbid diseases, and differences in the initial
      manifestations of the disease. Traditional risk factors for CHD include tobacco
      use, hypertension, diabetes mellitus, dyslipidemia, obesity, sedentary lifestyle,
      and atherogenic diet. More recently identified risk factors in women include high
      sensitivity C-reactive protein (hsCRP), homocysteine, and lipoprotein (a).
      Appropriate management of risk factors is associated with a reduced incidence of
      CHD, yet poor implementation in women is widely documented. Barriers to optimal
      risk factor management in women should be identified and overcome in an effort to
      maximize the cardiovascular health of women.

PMID- 14961453
TI  - Impact of gender on mortality following primary angioplasty for acute myocardial
      infarction.

PMID- 14961454
TI  - Outcomes of percutaneous and surgical revascularization in women.
AB  - There are gender-related differences both in the natural history of coronary
      artery disease (CAD) and in the response to revascularization strategies of
      patients with CAD. This paper reviews the specific pathophysiology of CAD in
      women as it influences outcome and current interventional and surgical treatment
      modalities and outcomes for stable and unstable coronary artery syndromes.

PMID- 14961455
TI  - The metabolic syndrome: an emerging health epidemic in women.
AB  - The metabolic syndrome is a compilation of factors characterized by insulin
      resistance and the identification of 3 of the 5 criteria of abdominal obesity,
      elevated triglycerides, decreased high-density lipoprotein (HDL) level, elevated
      blood pressure, and elevated fasting plasma glucose. According to census data
      from 2000, these criteria have lead to the diagnosis of approximately 47 million
      Americans with the metabolic syndrome, correlating with the 61% increase in the
      incidence of obesity between 1991 and 2000. Insulin resistance occurs when target
      tissues cannot respond properly to normal concentrations of insulin. The results
      are hypercoagulability, endothelial dysfunction, inflammation, and eventually
      coronary artery disease. Treatment involves lifestyle modification, including
      diet and exercise, to treat obesity and prevent the development of diabetes.
      Patients who meet the criteria for the metabolic syndrome may also be treated
      with insulin-sparing and insulin-sensitizing medications that help to improve
      endothelial function, vascular reactivity, and vascular inflammation. Ultimately,
      treatment goals are to prevent cardiovascular disease by both altering the risk
      factors that are components of the syndrome, and treating the lifestyle issues
      inherent to the disease process, such as caloric restriction and increased
      physical activity. There are 2 million more women than men in the United States
      categorized as being obese, with the trend of obesity and diabetes increasing. In
      the last decade there has been a 74% increase in obesity, mostly in women. This
      epidemic needs to be understood and managed to prevent further morbidity and
      mortality owing to diabetes and cardiovascular disease.

PMID- 14961456
TI  - Psychosocial factors in the development of coronary artery disease.
AB  - The fact that traditional risk factors only account for approximately two thirds
      of cases of coronary artery disease (CAD) has stimulated increasing interest in
      the relationship between CAD and psychosocial factors. Five areas--chronic
      stress, socioeconomic status (SES), personality, depression, and social support-
      have been most thoroughly examined. There is evidence to support a causal
      relationship between chronic stress, SES, depression, and social support and
      development of CAD. In this article, we discuss the epidemiologic evidence
      linking psychosocial factors and CAD, and review the effects of psychosocial
      factors on several pathophysiologic mechanisms that have been proposed as
      potential mediators of CAD. The hypothalamic-pituitary-adrenal axis, hypertension
      and cardiovascular reactivity, endothelial function, inflammatory markers,
      platelets, coagulation factors, fibrinogen, lipids, glucose metabolism, and
      lifestyle factors have all been implicated in this process. Recently, the first
      intervention trials have been carried out, although with initially disappointing
      results. Reducing the cardiovascular risk due to these psychosocial factors will
      be one of the major health care challenges in the future.

PMID- 14961457
TI  - Coronary vasospasm and the regulation of coronary blood flow.
AB  - Under physiologic conditions, epicardial arteries contribute minimally to
      coronary vascular resistance. However, in the presence of endothelial
      dysfunction, stimuli that normally produce vasodilation may instead cause
      constriction. Examples include neural release of acetylcholine or norepinephrine,
      platelet activation and production of serotonin and thrombin, and release of
      local factors such as bradykinin. This shift from a primary endothelial-mediated
      vasodilator influence to one of endothelial dysfunction and unchecked
      vasoconstriction is precisely the milieu in which coronary vasospasm is observed.
      This condition, which typically occurs during periods of relatively sedentary
      activity, is associated with focal and transient obstruction of an epicardial
      arterial segment resulting in characteristic echocardiographic changes and
      symptoms of myocardial ischemia. This review highlights the current understanding
      of mechanisms regulating the coronary circulation during health and examines the
      pathophysiologic changes that occur with coronary spasm. Genetic and other
      predisposing conditions are addressed, as well as novel therapies based on recent
      mechanistic insights of the coronary contractile dysfunction associated with
      coronary spasm.

PMID- 14961551
TI  - Loss of a single amino acid from dystrophin resulting in Duchenne muscular
      dystrophy with retention of dystrophin protein.
AB  - Almost all of the thousands of pathogenic mutations which have been described in
      the dystrophin gene either reduce protein production or remove large regions of
      the protein. This has severely limited the use of mutational information for the
      functional dissection of the dystrophin protein and increases the value of rare
      subtle mutations. We report a 3-bp deletion which removes a single highly
      conserved residue (glutamic acid 3367) adjacent to the dystrophin ZZ domain. This
      results in a phenotype of Duchenne muscular dystrophy with substantial retention
      of a presumably functionally compromised dystrophin protein. Two missense
      mutations (both affecting nearby residues) have been previously reported to
      result in this unusual combination of severe phenotype and high protein level. We
      discuss the functional implications of this and other mutations in the light of
      the predicted structure of the region. The pathogenicity of E3367del serves to
      emphasise the functional importance of this region of the dystrophin protein.

PMID- 14961552
TI  - Sodium channel gene (SCN5A) mutations in 44 index patients with Brugada syndrome:
      different incidences in familial and sporadic disease.
AB  - The Brugada syndrome (BS) is a distinct form of idiopathic ventricular
      fibrillation and may cause sudden cardiac death in healthy young individuals. In
      the surface ECG, BS can be recognized by an atypical right bundle branch block
      and ST-segment elevation in the right precordial leads. Mutations in the cardiac
      sodium channel gene SCN5A are only known to cause BS. In a multi-center effort,
      we have collected clinical data on 44 unrelated index patients and family members
      and performed a complete genetic analysis of SCN5A. In 37% the disease was
      familial, whereas in the majority it was sporadic (63%). Five novel SCN5A
      mutations (2602delC, resulting in: E867X; 2581_2582del TT: F861fs951X; 2673G>A:
      E1225K; 4435_4437delAAG: K1479del; and 5425C>A: S1812X) were found and were
      randomly located in SCN5A. Mutation frequencies (SCN5A+) differed significantly
      between familial (38%) and sporadic disease (0%) (p=0.001). Disease penetrance
      was complete in the SCN5A+ adult patients, but incomplete in SCN5A+ children
      (17%). Genetic testing of SCN5A is especially useful in familial disease to
      identify individuals at cardiac risk. In sporadic cases, however, a genetic basis
      and the value of mutation screening has to be further determined. These results
      are in line with a possibly genetic and clinical heterogeneity of BS.

PMID- 14961553
TI  - Alleles of polymorphic sites that correspond to hyperactive variants of CYP1B1
      protein are significantly less frequent in Japanese as compared to American and
      German populations.
AB  - CYP1B1 metabolites receive particular attention because of their causative role
      in malignant transformation of various steroid-related organs. Rare variants at
      residues c.701, c.1294 and c.1358 of CYP1B1 gene result in hyper-activity of
      protein and can lead to a higher susceptibility to estrogen-related cancers.
      However, in Japan, the incidences of estrogen-related cancers are remarkably
      lower than in Western countries. We hypothesize that polymorphisms of CYP1B1 gene
      can relate to lower incidence of estrogen-related diseases in the Japanese
      population. To test this hypothesis, the genetic distributions of six different
      CYP1B1 gene polymorphisms were evaluated among 200 Japanese, 200 Americans and
      112 Germans by an allele-specific PCR (ASP) technique. The frequencies of rare
      variants at residues c.701 and c.1294 were significantly lower in the Japanese
      population compared to that of other populations. 5.5% of Japanese showed the
      genotype 701T/T (versus 9.0% in Americans and 10.7% in Germans). 6.5% of Japanese
      showed the genotype 1294G/G (versus 14.5% in Americans and 12.5% in Germans). The
      polymorphism at residue c.1358 was not detected in the Japanese population
      although other populations showed the variant genotypes. This report clearly
      demonstrates rare variants that correspond to hyper-activity of CYP1B1 protein
      are significantly 1ess frequent in the Japanese population.

PMID- 14961554
TI  - Identification of variants in NFKBIA and association analysis with hepatocellular
      carcinoma risk among chronic HBV patients.
AB  - Human nuclear factor of kappa light chain gene enhancer in B cells inhibitor,
      alpha (NFKBIA) inhibits the action of NF-kappaB by forming a heterodimer with NF
      kappaB, and preventing its translocation to the nucleus. We have sequenced a
      human NFKBIA full gene including -1000bp promoter region to identify its gene
      polymorphisms as a potential candidate gene for host genetic study of
      Hepatocellular Carcinoma (HCC). Nine novel single nucleotide polymorphisms (SNPs)
      and one GAA deletion were identified; two in promoter region (c.-673A>T, c.
      642C>T), two in exon 1 (c.78G>A (Leu26Leu), c.81C>T (Asp27Asp)), three in introns
      (c.284T>A, c.1952A>G and c.2444C>T) and three in 3'UTR (c.2710-2712delGAA,
      c.2758G>A and c.3053G>A). Among ten identified variants, six were selected for
      larger scale genotyping (n=1,750) for association study based on frequencies and
      location. Haplotypes, their frequencies and linkage disequilibrium coefficients
      (/D'/) between SNP pairs were estimated. Allele frequencies of each SNPs and
      haplotypes were compared between patients with HCC and patients without HCC among
      HbsAg positives by logistic regression. As a conclusion, we could not find any
      significant association of NFKBIA variants with development of HCC among chronic
      hepatitis B patients.

PMID- 14961555
TI  - Single nucleotide polymorphisms and haplotype frequencies of CYP3A5 in a Japanese
      population.
AB  - In order to identify single nucleotide polymorphisms (SNPs) and haplotype
      frequencies of CYP3A5 in a Japanese population, we sequenced the proximal
      promoter region, all exons, and the surrounding intronic regions using genomic
      DNA from 187 Japanese subjects. Thirteen SNPs, including seven novel ones:
      13108T>C, 16025A>G, 16903A>G, 16993C>G, 27448C>A, 29782A>G, and 31551T>C (A of
      the translational start codon of GenBank Accession # NG_000004.2 is numbered 1
      according to the CYP Allele Nomenclature), were identified. The most common SNP
      was 6986A>G (key SNP for CYP3A5*3), with a 0.759 frequency. Two novel SNPs,
      29782A>G (I456V) and 31551T>C (I488T), as well as 12952T>C (*5 marker) were
      found, but these alterations were always associated with the *3A marker SNPs,
      6986A>G and 31611C>T. Using these 13 SNPs, haplotype analysis was performed and
      five novel *1 haplotypes (subtypes) (*1e to *1i) and six novel *3 haplotypes
      (subtypes) (*3d to *3i) were identified. Our findings suggest that CYP3A5*3 is
      the major defective allele and that other functional exonic SNPs are rare in the
      Japanese.

PMID- 14961556
TI  - Characterisation of a 161 kb deletion extending from the NBR1 to the BRCA1 genes
      in a French breast-ovarian cancer family.
AB  - A large germline deletion removing exons 1 to 22 of the BRCA1 gene has been
      previously detected using quantitative PCR based methods (QMPSF and real time PCR
      gene dosage assay) in a woman affected with breast and ovarian cancer. Here, we
      report its characterisation by using colour bar code on combed DNA of the BRCA1
      region. The 5' boundary is located in a Alu Y sequence in NBR1 intron 18 whereas
      the 3' boundary is located in a Alu Sc sequence in BRCA1 intron 22. This 161 kb
      deletion encompassing the NBR1, PsiBRCA1, NBR2 and BRCA1 genes is the largest
      BRCA1 deletion reported so far. No specific phenotype was associated with the
      hemizygosity of these four genes.

PMID- 14961557
TI  - A novel PTPN11 mutation in LEOPARD syndrome.
AB  - PTPN11 gene mutations are common to both patients with Noonan (NS) and LEOPARD
      syndrome (LS). So far only two recurrent mutations have been identified in LS
      patients by different research groups, i.e., Tyr279Cys and Thr468Met. In this
      work we describe the third PTPN11 mutation that has been found in a single LS
      patient. The mutation (c.1517A>C) substitutes a proline for a glutamine at amino
      acid 506 (Gln506Pro) in the phosphatase domain (PTP) of the PTPN11 peptide SHP2.
      This region is a mutation hotspot. Changes at amino acids 501 to 504 cause NS.
      Gln506Pro is predicted, by modeling analysis, to seriously disrupt the normal
      contacts between the regulating N-SH2 and the active PTP domains, leading to
      hyperactivity of the phosphatase. This report demonstrates that rarer mutations
      other than Tyr279Cys and Thr468Met can be found in LS patients and the need of
      screening the whole gene in those negative for the commonest mutations.

PMID- 14961558
TI  - Identification of four novel melanocortin 1 receptor (MC1R) gene variants in a
      Mediterranean population.
AB  - The melanocortin 1 receptor (MC1R) gene is a major determinant of human
      pigmentation and specific allelic variants have been associated with red hair and
      sun sensitive skin types as well as increased skin cancer risk in Caucasian
      individuals. We screened for allelic variants the entire MC1R coding region of
      100 unrelated individuals sampled from an Italian population who has darker
      pigmentary traits than populations analyzed to date. Twenty MC1R variants were
      identified, eighteen located at non-synonymous sites and two at synonymous sites.
      We report four novel MC1R allelic variants: C35Y (g.104G>A), V38M (g.112G>A),
      L44V (g.130C>G) and I120T (g.359T>C).

PMID- 14961559
TI  - The mutation spectrum of the APC gene in FAP patients from southern Italy:
      detection of known and four novel mutations.
AB  - Familial adenomatous polyposis (FAP), an autosomal dominantly inherited condition
      accounting for about 1% of all colorectal cancers, results from mutations in the
      adenomatous polyposis coli (APC) tumor suppressor gene. The clinical spectrum and
      severity of FAP varies greatly with the mutation site, and both between and
      within families. Using the protein truncation test, single strand conformation
      polymorphism analysis and DNA sequencing, we identified 30 (75%) mutant alleles
      in 40 unrelated FAP families, for a total of 22 different APC mutations. Of
      these, 18 are known and 4 are novel: c.1797C>A (C599X), c.893_894delAC,
      (c.3225T>A; c.3226C>A) and c.4526_4527insT. Of the 30 APC gene mutations, 5
      (approximately 17%) are nonsense mutations, 17 (approximately 57%) are small
      deletions, 5 (approximately 17%) are small insertions and 3 (approximately 10%)
      are complete deletions. All mutations occurred in single pedigrees, except those
      at codons 1061 and 1062, each found in two unrelated families, and the mutation
      at codon 1309 in exon 15, found in five unrelated families. About 40% of
      mutations, mostly small deletions and insertions, are located at repeated
      sequences; they promote misalignment-mediated errors in DNA replication and could
      represent a hot spot mutation region. This study enlarges the spectrum of APC
      gene mutations and sheds light on the correlation between the site of APC
      germline mutations and clinical manifestations of FAP.

PMID- 14961560
TI  - Fourteen novel OPA1 mutations in autosomal dominant optic atrophy including two
      de novo mutations in sporadic optic atrophy.
AB  - The OPA1 gene, encoding a dynamin-related GTPase that plays a role in
      mitochondrial biogenesis, is implicated in most cases of autosomal dominant optic
      atrophy (ADOA). Sixty-nine pathogenic OPA1 mutations have been reported so far.
      Most of these are truncating mutations located in the GTPase domain coding region
      (exons 8-16) and at the 3'-end (exons 27-28). We screened 44 patients with
      typical ADOA using PCR-sequencing. We also tested 20 sporadic cases of bilateral
      optic atrophy compatible with ADOA. Of the 18 OPA1 mutations found, 14 have never
      been previously reported. The novel mutations include one nonsense mutation, 3
      missense mutations, 6 deletions, one insertion and 3 exon-skipping mutations. Two
      of these are de novo mutations, which were found in 2 patients with sporadic
      optic atrophy. The recurrent c.2708_2711delTTAG mutation was found in 2 patients
      with a severe congenital presentation of the disease. These results suggest that
      screening for OPA1 gene mutations may be useful for patients with optic atrophy
      who have no affected relatives, or when the presentation of the disease is
      atypical as in the case of early onset optic atrophy.

PMID- 14961561
TI  - Comparative cellular distribution of GABAA and GABAB receptors in the human basal
      ganglia: immunohistochemical colocalization of the alpha 1 subunit of the GABAA
      receptor, and the GABABR1 and GABABR2 receptor subunits.
AB  - The GABA(B) receptor is a G-protein linked metabotropic receptor that is
      comprised of two major subunits, GABA(B)R1 and GABA(B)R2. In this study, the
      cellular distribution of the GABA(B)R1 and GABA(B)R2 subunits was investigated in
      the normal human basal ganglia using single and double immunohistochemical
      labeling techniques on fixed human brain tissue. The results showed that the
      GABA(B) receptor subunits GABA(B)R1 and GABA(B)R2 were both found on the same
      neurons and followed the same distribution patterns. In the striatum, these
      subunits were found on the five major types of interneurons based on morphology
      and neurochemical labeling (types 1, 2, 3, 5, 6) and showed weak labeling on the
      projection neurons (type 4). In the globus pallidus, intense GABA(B)R1 and
      GABA(B)R2 subunit labeling was found in large pallidal neurons, and in the
      substantia nigra, both pars compacta and pars reticulata neurons were labeled for
      both receptor subunits. Studies investigating the colocalization of the GABA(A)
      alpha(1) subunit and GABA(B) receptor subunits showed that the GABA(A) receptor
      alpha(1) subunit and the GABA(B)R1 subunit were found together on GABAergic
      striatal interneurons (type 1 parvalbumin, type 2 calretinin, and type 3 GAD
      neurons) and on neurons in the globus pallidus and substantia nigra pars
      reticulata. GABA(B)R1 and GABA(B)R2 were found on substantia nigra pars compacta
      neurons but the GABA(A) receptor alpha(1) subunit was absent from these neurons.
      The results of this study provide the morphological basis for GABAergic
      transmission within the human basal ganglia and provides evidence that GABA acts
      through both GABA(A) and GABA(B) receptors. That is, GABA acts through GABA(B)
      receptors, which are located on most of the cell types of the striatum, globus
      pallidus, and substantia nigra. GABA also acts through GABA(A) receptors
      containing the alpha(1) subunit on specific striatal GABAergic interneurons and
      on output neurons of the globus pallidus and substantia nigra pars reticulata.

PMID- 14961562
TI  - Neurochemical characterization of extrinsic innervation of the guinea pig rectum.
AB  - The presence of markers for parasympathetic, sympathetic, and glutamatergic or
      peptidergic sensory innervation was investigated by using in vitro tracing with
      biotinamide, combined with immunohistochemistry, to characterise quantitatively
      extrinsic axons to myenteric ganglia of the guinea pig rectum. Of biotinamide
      filled varicose axons, 3.6 +/- 1.3% were immunoreactive for tyrosine hydroxylase
      (TH) and 16.0 +/- 4.8% for vesicular acetylcholine transporter (VAChT). TH and
      vesicular monoamine transporter (VMAT1) showed high coexistence (83-100%),
      indicating that varicosities lacking TH immunoreactivity also lacked VMAT1. VAChT
      was detectable in 77% of choline acetyltransferase (ChAT)-immunoreactive
      varicosities. Calcitonin gene-related peptide (CGRP) was detected in 5.3 +/- 1.6%
      of biotinamide-labeled varicosities, the vesicular glutamate transporter (VGluT)
      1 in 2.8 +/- 0.8%, and VGluT2 in 11.3 +/- 4.2% of varicosities of extrinsic
      origin. Varicosities from the same axon showed consistent immunoreactivity. A
      novel type of nerve ending was identified, with branching, flattened lamellar
      endings, similar to the intraganglionic laminar endings (IGLEs) of the proximal
      gut. Rectal IGLEs were frequently immunoreactive for VGluT1 and VGluT2. Thus most
      varicose axons of extrinsic origin, which innervate rectal myenteric ganglia,
      lack detectable levels of immunoreactivity for TH, VMAT1, VAChT, ChAT, VGluT1/2,
      or CGRP, under conditions in which these markers are readily detectable in other
      axons. Although some unlabeled varicosities may belong to afferent axons that
      lack detectable CGRP or VGluT1/2 in the periphery, this suggests that a large
      proportion of axons do not release any of the major autonomic or sensory
      transmitters. We speculate that this may vary under particular circumstances, for
      example, inflammation or obstruction of the gut.

PMID- 14961563
TI  - AII amacrine cells in the mammalian retina show disabled-1 immunoreactivity.
AB  - Disabled 1 (Dab1) is an adapter molecule in a signaling pathway, stimulated by
      Reelin, which controls cell positioning in the developing brain. It has been
      localized to AII amacrine cells in the mouse and guinea pig retinas. This study
      was conducted to identify whether Dab1 is commonly localized to AII amacrine
      cells in the retinas of other mammals. We investigated Dab1-labeled cells in
      human, rat, rabbit, and cat retinas in detail by immunocytochemistry with
      antisera against Dab1. Dab1 immunoreactivity was found in certain populations of
      amacrine cells, with lobular appendages in the outer half of the inner plexiform
      layer (IPL) and a bushy, smooth dendritic tree in the inner half of the IPL.
      Double-labeling experiments demonstrated that all Dab1-immunoreactive amacrine
      cells were immunoreactive to antisera against calretinin or parvalbumin (i.e.,
      other markers for AII amacrine cells in the mammalian retina) and that they made
      contacts with the axon terminals of the rod bipolar cells in the IPL close to the
      ganglion cell layer. Furthermore, all Dab1-labeled amacrine cells showed glycine
      transporter-1 immunoreactivity, indicating that they are glycinergic. The peak
      density was relatively high in the human and rat retinas, moderate in the cat
      retina, and low in the rabbit retina. Together, these morphological and
      histochemical observations clearly indicate that Dab1 is commonly localized to
      AII amacrine cells and that antiserum against Dab1 is a reliable and specific
      marker for AII amacrine cells of diverse mammals.

PMID- 14961564
TI  - Microglial major histocompatibility complex glycoprotein-1 in the axotomized
      facial motor nucleus: regulation and role of tumor necrosis factor receptors 1
      and 2.
AB  - Presentation of antigen is key to the development of the immune response,
      mediated by association of antigen with major histocompatibility complex
      glycoproteins abbreviated as MHC1 and MHC2. In the current study, we examined the
      regulation of MHC1 in the brain after facial axotomy. The normal facial motor
      nucleus showed no immunoreactivity for MHC1 (MHC1-IR). Transection of the facial
      nerve led to a strong and selective up-regulation of MHC1-IR on the microglia in
      the affected nucleus, beginning at day 2 and reaching a maximum 14 days after
      axotomy, coinciding with a peak influx of the T lymphocytes that express CD8, the
      lymphocyte coreceptor for MHC1. Specificity of the MHC1 staining was confirmed in
      beta2-microglobulin-deficient mice, which lack normal cell surface MHC1-IR. MHC1
      IR was particularly strong on phagocytic microglia, induced by delayed neuronal
      cell death, and correlated with the induction of mRNA for tumor necrosis factor
      (TNF)-alpha, interleukin (IL)-1beta, and interferon-gamma and the influx of T
      lymphocytes. Mice with severe combined immunodeficiency (scid), lacking T and B
      cells, showed an increase in the number of MHC1-positive nodules but no
      significant effect on overall MHC1-IR. Transgenic deletion of the IL1 receptor
      type I, or the interferon-gamma receptor type 1 subunit, did not affect the
      microglial MHC1-IR. However, a combined deletion of TNF receptors 1 and 2
      (TNFR1&2-KO) led to a decrease in microglial MHC1-IR and to a striking absence of
      the phagocytic microglial nodules. Deletion of TNFR2 (p75) did not have an
      effect; deletion of TNFR1 (p55) reduced the diffuse microglial staining for MHC1
      IR but did not abolish the MHC1(+) microglial nodules. In summary, neural injury
      leads to the induction of MHC1-IR on the activated, phagocytic microglia. This
      induction of MHC1 precedes the interaction with the immune system, at least in
      the facial motor nucleus model. Finally, the impaired induction of these
      molecules, up to now, only in the TNFR-deficient mice underscores the central
      role of TNF in the immune activation of the injured nervous system.

PMID- 14961565
TI  - Immunoreactive TRPV-2 (VRL-1), a capsaicin receptor homolog, in the spinal cord
      of the rat.
AB  - The vanilloid receptor-like 1 protein (VRL-1, also called TRPV2) is a member of
      the TRPV family of proteins and is a homolog of the capsaicin/vanilloid receptor
      (VR1, or TRPV1). Although VRL-1 does not bind capsaicin, like VR1 it is activated
      by noxious heat (>52 degrees C). Unlike VR1, however, VRL-1 is primarily
      expressed by medium- and large-diameter primary afferents, which suggests that
      nociceptive processing is but one of the functions to which VRL-1 contributes. To
      provide information on the diverse spinal circuits that are engaged by these VRL
      1-expressing primary afferents, we completed a detailed immunocytochemical map of
      VRL-1 in rat spinal cord, including light and electron microscopic analysis, and
      generated a more comprehensive neurochemical characterization of VRL-1-expressing
      primary afferents. Consistent with previous reports, we found that VRL-1 and VR1
      are expressed in different dorsal root ganglion (DRG) cell bodies. Almost all VRL
      1-expressing cells labeled for N52 (a marker of myelinated afferents), consistent
      with VRL-1 expression in Adelta and Abeta fibers. EM analysis of the DRG and
      dorsal roots confirmed this and revealed two categories of neurons based on the
      intensity of immunolabeling. The densest VRL-1 immunoreactivity in the spinal
      cord was found in lamina I, inner lamina II, and laminae III/IV. This is
      consistent with the expression of VRL-1 by myelinated nociceptors that target
      laminae I and IIi and in nonnociceptive Abeta fibers that target laminae III/IV.
      Dorsal rhizotomy reduced, but did not eliminate, the immunostaining in all dorsal
      horn laminae, which indicates that VRL-1 expression derives from both DRG cells
      and from neurons intrinsic to the brain or spinal cord. Spinal hemisection
      reduced immunostaining of the ipsilateral dorsal columns in segments rostral to
      the lesion and in the dorsal column nuclei, presumably from the loss of ascending
      Abeta afferents, but there was no change caudal to the lesion. Thus, supraspinal
      sources of dorsal horn VRL-1 immunoreactivity are likely not significant.
      Although we never observed VRL-1 immunostaining in cell bodies in the superficial
      dorsal horn, there was extensive labeling of motoneurons and ventral root
      efferents-in particular, in an extremely densely labeled population at the
      lumbosacral junction. Finally, many ependymal cells surrounding the central canal
      were intensely labeled. These results emphasize that VRL-1, in contrast to VR1,
      is present in a diverse population of neurons and undoubtedly contributes to
      numerous functions in addition to nociceptive processing.

PMID- 14961566
TI  - Quantitative morphological analysis of the motoneurons innervating muscles
      involved in tongue movements of the frog Rana esculenta.
AB  - We give an account of an effort to make quantitative morphological distinctions
      between motoneurons of the frog innervating functionally different groups of
      muscles involved in the movements of the tongue. The protractor, retractor, and
      inner muscles of the tongue were considered on the basis of their major action
      during the prey-catching behavior of the frog. Motoneurons were selectively
      labeled with cobalt lysin through the nerves of the individual muscles, and
      dendritic trees of successfully labeled neurons were reconstructed. Each
      motoneuron was characterized by 15 quantitative morphological parameters
      describing the size of the soma and dendritic tree and 12 orientation variables
      related to the shape and orientation of the dendritic field. The variables were
      subjected to multivariate discriminant analysis to find correlations between form
      and function of these motoneurons. According to the morphological parameters, the
      motoneurons were classified into three functionally different groups weighted by
      the shape of the perikaryon, mean diameter of stem dendrites, and mean length of
      dendritic segments. The most important orientation variables in the separation of
      three groups were the ellipses describing the shape of dendritic arborization in
      the horizontal, frontal, and sagittal planes of the brainstem. These findings
      indicate that characteristic geometry of the dendritic tree may have a preference
      for one array of fibers over another.

PMID- 14961567
TI  - Poly(ADP-ribose) polymerase-1, a novel partner of progesterone receptors in
      endometrial cancer and its precursors.
AB  - Endometrial carcinomas are the most common malignancy of the female genital
      tract. Although the downregulation of the progesterone receptor (PR) in the
      progression of endometrioid carcinomas (ECs) has been well documented, the
      mechanism of PR alteration in endometrioid carcinogenesis is poorly understood.
      Recently, biochemical studies have shown that the DNA strand break-sensing
      molecule poly(ADP-ribose) polymerase (PARP-1) was associated with the DNA binding
      domain of PR. In our present study, we show that in normal endometrial
      epithelium, the expression level of PARP-1 protein is high in the proliferative
      phase but markedly decreases during the secretory phase. Interestingly, PARP-1
      expression gradually increases in nonatypical and atypical endometrial
      hyperplasia, reaching its highest level in grade I, and decreases significantly
      toward grade III ECs. Notably, PARP-1 and PR expressions, in each stage, are
      positively correlated (p < 0.0001), with the exception of nonendometrioid
      carcinomas. Thus, these data suggest that PARP-1 is substantially involved in the
      regulation of progesterone action in the development of ECs.

PMID- 14961568
TI  - Preclinical evaluation of the nonsteroidal anti-inflammatory agent celecoxib on
      malignant mesothelioma chemoprevention.
AB  - Malignant mesothelioma (MM) remains the most lethal pleural, peritoneal and
      pericardial cancer. Here, we characterize the effects of nonsteroidal anti
      inflammatory agents (NSAIDs) on in vitro and in vivo experimental MM models.
      Unlike primary normal mesothelial cells, the selective cyclooxygenase (COX)-2
      inhibitor celecoxib reduced the in vitro proliferation of several MM cells
      derived from previously untreated MM patients. Moreover, celecoxib significantly
      inhibited MM cell colony formation in soft agarose (63-78% at 5 x 10(-5) M; p <
      or = 0.05) and it elicited remarkable antitumor activity, leading to long-term
      survival in >37% of nude mice bearing intraperitoneal MM. Celecoxib was more
      efficient in inhibiting MM cell growth than acetylsalicylic acid (10(-6) M-10(-2)
      M), indometacin (10(-6) M-10(-2) M) and the COX-2 inhibitor NS-398 (10(-6) M-10(
      4) M). Efficacy of these different compounds was not related to the amount of COX
      2 protein levels present on MM cells. Celecoxib, in a dose- and time-dependent
      manner, induced MM cell apoptosis, which involved decreased Akt phosphorylation,
      loss of Bcl-2 and Survivin protein expression and caspase-3 activation.
      Furthermore, vascular endothelial growth factor (VEGF), an MM autocrine growth
      factor and Akt inducer, rescued celecoxib-induced apoptosis and Akt
      dephosphorylation. When the VEGF receptor (KDR/Flk-1) inhibitor, SU-1498, was
      used in combination with celecoxib, IC50 of celecoxib in vitro was reduced up to
      65%. These data demonstrate that celecoxib may have antitumor properties in MM
      and provide a rationale for the therapeutic use of celecoxib in combination with
      a selective VEGF inhibitor.

PMID- 14961569
TI  - Loss of PKR activity in chronic lymphocytic leukemia.
AB  - There are a number of observations that suggest the dsRNA-activated protein
      kinase, PKR, may play an active role in formation and maintenance of leukemia,
      including nonrandom chromosomal deletions in acute leukemia as well as
      truncations and deletions of the PKR gene in some leukemia cell lines. However,
      there is little direct evidence from patient material that this is so. Here we
      show that full-length PKR is present but not active in 21 of 28 patient samples
      from B-cell chronic lymphocytic leukemia (B-CLL). PKR from these patients was
      unable to auto-activate or phosphorylate substrates but was able to bind dsRNA.
      Furthermore, the lack of PKR activation was not due to differing levels of the
      PKR activator, PACT nor of the PKR inhibitor, p58(IPK). We compared PKR status
      with clinical parameters and disease staging. No differences were found between
      the 2 groups in terms of staging (modified Rai or Binet), age, CD38 status, p53
      status, 11q23 deletion status or CEP12 deletion status. However, there was a
      significant correlation between deletion in 13q14.3 and lack of PKR activity. We
      show that B-CLL cells appear to contain a soluble inhibitor of PKR, as lysates
      from cells lacking PKR activity were able to inhibit exogenous PKR in mixing
      experiments. Finally, we show suppression of PKR activity was still present
      following ultrafilitration through a 10,000 Da cutoff filter but was lost upon
      extraction with phenol/chloroform or by high salt washing. This data suggests
      loss of PKR activity may contribute to the formation and/or maintenance of CLL.

PMID- 14961570
TI  - Genetic downregulation of pregnancy-associated plasma protein-A (PAPP-A) by
      bikunin reduces IGF-I-dependent Akt and ERK1/2 activation and subsequently
      reduces ovarian cancer cell growth, invasion and metastasis.
AB  - A Kunitz-type protease inhibitor, bikunin, downregulates expression of uPA and
      its receptor uPAR at the mRNA and protein levels in several types of tumor cells.
      Our recent work showed that, using a cDNA microarray analysis, pregnancy
      associated plasma protein-A (PAPP-A) is a candidate bikunin target gene. To
      clarify how reduced levels of PAPP-A may confer repressed invasiveness, we
      transfected human ovarian cancer cell line HRA with antisense (AS)-PAPP-A cDNA
      and compared the properties of the transfected cells to those of parental HRA
      cells. Here, we show that regulation of uPA mRNA and protein by IGF-I depends on
      the PI3K and MAPK signaling pathways and phosphorylation of Akt and ERK1/2 is
      required for IGF-I-mediated cell invasion; that IGFBP-4 protease in HRA cells is
      identified as PAPP-A; that reduced PAPP-A expression is associated with the
      upregulation of IGFBP-4 expression; that higher intact IGFBP-4 levels were
      associated with low invasive potential and growth rate in AS-PAPP-A cells in
      response to IGF-I; that IGF-I stimulates Akt and ERK1/2 activation of both the
      control and antisense cells, but the relative potency and efficacy of IGF-I were
      lower in the antisense cells compared to the control; and that genetic
      downregulation of PAPP-A reduces the proliferation, invasion and metastasis of
      HRA cells. In conclusion, our data identify a novel role for PAPP-A as a bikunin
      target gene. IGF-I-induced IGFBP-4 proteolysis by PAPP-A may enhance cell growth
      and invasion through IGF-I-dependent Akt and ERK1/2 activation and subsequently
      upregulation of uPA.

PMID- 14961571
TI  - -160C/A polymorphism in the E-cadherin gene promoter and risk of hereditary,
      familial and sporadic prostate cancer.
AB  - The E-cadherin (CDH1) gene has been associated with prostate carcinogenesis. The
      C/A polymorphism--160 base pairs relative to the transcription start site has
      been shown to decrease gene transcription. We analyzed the association between
      this polymorphism and the risk of sporadic, familial (2 close relatives) and
      hereditary (3 or more close relatives) prostate cancer. We combined data from 3
      population-based epidemiologic studies in Sweden encompassing altogether 1,036
      prostate cancer cases and 669 controls that were genotyped for the short
      nucleotide polymorphism. Odds ratios with 95% confidence intervals were estimated
      through unconditional logistic regression. We found no significant association
      between the A-allele and sporadic (OR = 1.0; 95% CI = 0.8-1.2) or familial (OR =
      1.4; 95% CI = 0.9-2.2) prostate cancer. In contrast, risk of hereditary cancer
      was increased among heterozygote CA carriers (OR = 1.7; 95% CI = 1.0-2.7) and
      particularly among homozygote AA carriers (OR = 2.6; 95% CI = 1.4-4.9). Our data
      indicate that the -160 single nucleotide polymorphism in CDH1 is a low-penetrant
      prostate cancer susceptibility gene that might explain a proportion of familial
      and notably hereditary prostate cancer.

PMID- 14961572
TI  - Polymorphisms of the interleukin-1 beta gene are associated with increased risk
      of non-small cell lung cancer.
AB  - Lung cancer is one of the leading causes of cancer death worldwide. Tobacco
      smoking is the main risk factor for lung cancer. Less than 20% of smokers develop
      lung cancer in their lifetime, however, indicating individual variations in lung
      cancer risk. Pro-inflammatory cytokines produced by inflammatory cells have been
      associated with inflammatory diseases and cancer. The IL1B gene, encoding IL
      1beta cytokine, contains several single nucleotide polymorphisms (SNPs). Two of
      these are in the promoter region, at positions -511 (C-T) and -31 (T-C). These
      polymorphisms have been associated with increased risk of developing a number of
      inflammatory diseases and gastric carcinoma. We genotyped the 2 polymorphisms in
      251 non-small cell lung cancer patients from Norway and 272 healthy controls
      chosen from the general Norwegian population. The T allele at the -31 SNP (p =
      0.01) and C allele at -511 SNP (p < 0.01) were over represented in lung cancer
      cases. The homozygote subjects were particularly at higher risk of lung cancer
      with odds ratio of 2.39 (95% CI = 1.29-4.44) for -31T/T and 2.51 (95% CI = 1.47
      4.58) for -511C/C genotypes. In view of the significance of the p53 gene in lung
      carcinogenesis, we also analyzed the IL1B genotypes in relation to p53 mutations
      in the tumors. The results indicated that subjects having homozygote genotypes
      were more likely to have a mutation in the p53 gene (p = 0.05). This is the first
      study to provide evidence for an association of 1L1B gene polymorphisms with lung
      cancer risk.

PMID- 14961573
TI  - Chromosome 13q12 region critical for the viability and growth of nasopharyngeal
      carcinoma hybrids.
AB  - Allelic losses of chromosome 13 are often detected in nasopharyngeal carcinoma
      (NPC) and other cancers, implicating the presence of possible tumor suppressor
      genes (TSGs) on this chromosome. To identify candidate regions from larger and
      multiple lost areas observed from direct tumor studies, the technique of
      monochromosome transfer was utilized to provide functional evidence to verify and
      define these deletion findings. An intact chromosome 13 was transferred into the
      NPC HONE1 cell line. Resultant hybrids were used to map putative TSG activity. A
      critical region at 13q12 was non-randomly eliminated in all surviving microcell
      hybrids around the marker D13S893; these hybrids were uniformly tumorigenic.
      Although a known TSG, BRCA2, is mapped close to this critical region, no aberrant
      expression of this gene was detected in microcell hybrids and other NPC cell
      lines. These results suggest that at least one novel growth control gene on
      chromosome 13q12, which is not the BRCA2 gene, is essential for hybrid selection
      and may play a critical role in tumorigenicity.

PMID- 14961574
TI  - Amplification of chromosome 1 sequences in lipomatous tumors and other sarcomas.
AB  - Amplifications and gains involving 1q are common abnormalities in solid tumors.
      Recently, an amplicon originating from 1q21-23, containing the candidate
      oncogenes COAS1, COAS2 and COAS3 (Chromosome One Amplified Sequence) was
      identified. The presence, distribution and copy number level of extra COAS
      sequences were investigated in 48 bone and soft tissue tumor (BSTT) samples using
      metaphase FISH analysis. Amplification was seen in 27/48 (56%) samples. With few
      exceptions, all 3 genes were involved, but on average COAS2 exhibited higher copy
      numbers. The presence of extra COAS signals, irrespective of copy numbers, was
      found at similar frequencies in different histologic tumor subtypes. However,
      medium or high level amplification was common in lipomatous tumors but rare in
      other, nonlipomatous tumors (9/21 vs. 2/27 samples). The most common localization
      of extra COAS signals in lipomatous tumors was in supernumerary ring and giant
      marker chromosomes. Among nonlipomatous tumors, the distribution of extra COAS
      genes was more disperse, being located in various unidentified chromosomal
      structures, including double minutes, and only rarely in ring chromosomes.
      Because MDM2 is known to be amplified frequently in BSTTs, and in particular in
      atypical lipomatous tumors, cases with extra copies of COAS were studied also
      with an MDM2 probe. Twelve out of 18 lipomatous tumors had extra copies of both
      COAS and MDM2, and the 2 genes were found to be coamplified and interspersed
      exclusively in ring and giant marker chromosomes. Also 12 out of 18 nonlipomatous
      tumors exhibited simultaneous gain of COAS and MDM2, but colocalization in the
      same chromosome was less frequent. The role of the frequent coamplification of
      COAS, or some other yet unknown gene in the 1q21-23 region, and MDM2 remains to
      be elucidated.

PMID- 14961575
TI  - Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double
      primary cancers of the colorectum and the endometrium: a population-based study
      in northern Sweden.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant
      disorder that predisposes to predominantly colorectal and endometrial cancers due
      to germline mutations in DNA mismatch repair genes, mainly MLH1, MSH2 and in
      families with excess endometrial cancer also MSH6. In this population-based
      study, we analysed the mutation spectrum of the MLH1, MSH2 and MSH6 genes in a
      cohort of patients with microsatellite unstable double primary tumours of the
      colorectum and the endometrium by PCR, DHPLC and sequencing. Fourteen of the 23
      patients (61%) had sequence variants in MLH1, MSH2 or MSH6 that likely affect the
      protein function. A majority (10/14) of the mutations was found among probands
      diagnosed before age 50. Five of the mutations (36%) were located in MLH1, 3
      (21%) in MSH2 and 6 (43%) in MSH6. MSH6 seem to have larger impact in our
      population than in other populations, due to a founder effect since all of the
      MSH6 families originate from the same geographical area. MSH6 mutation carriers
      have later age of onset of both colorectal cancer (62 vs. 51 years) and
      endometrial cancer (58 vs. 48 years) and a larger proportion of endometrial
      cancer than MLH1 or MSH2 mutation carriers. We can conclude that patients with
      microsatellite unstable double primary cancers of the colorectum and the
      endometrium have a very high risk of carrying a mutation not only in MLH1 or MSH2
      but also in MSH6, especially if they get their first cancer diagnosis before the
      age of 50.

PMID- 14961576
TI  - Frequent alterations of Ras signaling pathway genes in sporadic malignant
      melanomas.
AB  - Ras signaling is important for the intracellular transduction of mitogenic
      stimuli from activated growth factor receptors. We have investigated 37 sporadic
      malignant melanomas (15 primary cutaneous melanomas and 22 melanoma metastases)
      and 6 melanoma cell lines for mutations in the 3 Ras genes NRAS, KRAS and HRAS.
      All tumors and cell lines were additionally analyzed for mutation and expression
      of BRAF, which encodes a Ras-regulated serine/threonine kinase with oncogenic
      properties, as well as for expression of RASSF1A, which encodes a Ras-binding
      protein with tumor suppressor properties. Mutational analyses identified somatic
      NRAS mutations in 2 primary melanomas, 4 melanoma metastases and 2 cell lines.
      One melanoma metastasis showed a somatic KRAS mutation whereas HRAS mutations
      were not detected. Eight primary melanomas, 6 melanoma metastases and 4 melanoma
      cell lines carried BRAF mutations affecting the known hot-spot codon 599. None of
      the tumors or cell lines with BRAF mutation demonstrated NRAS or KRAS mutations.
      Real-time reverse transcription-PCR showed that 8 melanomas (3 primary tumors, 5
      melanoma metastases) had reduced RASSF1A transcript levels of < or =50% relative
      to benign melanocytic nevi and normal skin. Three melanoma cell lines lacked
      detectable RASSF1A transcripts. The RASSF1A gene promoter was hypermethylated in
      these 3 cell lines as well as in 6 of 8 melanomas with reduced RASSF1A mRNA
      levels. Treatment of the cell lines with 5-aza-2'-deoxycytidine and trichostatin
      A resulted in demethylation of the RASSF1A promoter and re-expression of RASSF1A
      transcripts. Most tumors and all cell lines with RASSF1A promoter methylation
      additionally carried BRAF or NRAS mutations, suggesting a synergistic effect of
      these aberrations on melanoma growth. Taken together, 57% of the investigated
      melanomas and 100% of the melanoma cell lines carried mutations in either NRAS,
      KRAS or BRAF. In addition, 22% of the melanomas and 50% of the cell lines showed
      reduced RASSF1A transcript levels. Thus, alterations of Ras pathway genes are of
      paramount importance in the pathogenesis of sporadic melanomas.

PMID- 14961577
TI  - WT1 is a tumor-associated antigen in colon cancer that can be recognized by in
      vitro stimulated cytotoxic T cells.
AB  - The Wilms' tumor suppressor gene (WT1) has been shown to be overexpressed in
      acute and chronic leukemias and in a variety of solid human malignancies,
      including cancers of the breast and lung. In our present study, we investigated
      the potential role of WT1 gene in human colon cancer. WT1 mRNA and protein
      expression was analyzed in a panel of human colon cancer cell lines and primary
      colon carcinomas by RT-PCR and Western blot analysis, respectively. A mutational
      screen of WT1' zinc-finger region was carried out by sequence analysis. Finally,
      using peptide-stimulated cytotoxic T cells it was investigated whether WT1
      expressing colon tumor cells are a potential target for antigen-specific
      immunotherapy. Medium to high abundant levels of WT1 mRNA were detected by RT-PCR
      in 10 of 12 (83%) colon cell lines and by quantitative, real-time RT-PCR in 13 of
      15 (87%) primary tumors, whereas only very low levels of expression were found in
      2 primary tumors. Interestingly, however, low levels of WT1 mRNA were also
      detected in all samples derived from normal colon mucosa. When RT-PCR products
      were examined by sequence analysis, both +KTS and -KTS splice isoforms but no
      zinc-finger mutations were found, suggesting that the wild-type form of the WT1
      gene is expressed. To determine whether the WT1 protein can serve as a target
      antigen for immunotherapy, 2 HLA-A2.1-restricted WT1 peptides (Db126 and WH187)
      were used for the in vitro induction of WT1-specific cytotoxic T lymphocytes
      (CTLs). The WH187-specific CTLs not only lysed target cells pulsed exogenously
      with cognate peptide but also WT1-expressing colon tumor cells in a HLA
      restricted manner. These findings identify the WT1 protein as an attractive
      target for the development of antigen-specific immunotherapy in human colon
      cancer.

PMID- 14961578
TI  - Analysis of the natural killer mediated immune response in metastatic renal cell
      carcinoma patients.
AB  - Metastatic renal cell carcinomas (MRCC) are considered as immunogeneic tumors on
      the basis of the clinical responses observed in patients treated by IL-2.
      However, renal cell carcinoma patients are also characterized by alterations of
      the immune response that may compromise the immunotherapeutic approaches. In our
      study, we have studied the phenotype and the functional capacities of peripheral
      NK cells in a panel of neprectomized metastatic renal cell carcinoma patients. NK
      cells were harvested by negative immunoselection from fresh peripheral blood
      samples. In most of MRCC patients analysed (23/28), the expression of NCR (NKp46
      and NKp30) was similar to that of donors. Lytic capacities by activated
      immunoselected NK cells from MRCC patients assessed against K562 and 3 renal
      tumor cell lines were in the range of that observed in NK cells from normal
      donors. HLA-I- renal tumor cells UOK23 were killed with a good efficiency,
      whereas HLA-I renal tumor cells were more resistant. Although LFA-1/ICAM-1
      interaction potentiates RCC cell lysis, HLA-I/NKR interaction clearly decreased
      RCC cell susceptibility to NK cells. In addition, proliferation of NK cells from
      MRCC patients in response to cytokines was altered.

PMID- 14961579
TI  - CD1d is expressed on B-chronic lymphocytic leukemia cells and mediates alpha
      galactosylceramide presentation to natural killer T lymphocytes.
AB  - Generation of immune responses against B cell chronic lymphocytic leukemia (B
      CLL) has been the aim of several studies that have demonstrated a poor antigen
      presenting ability of B-CLL cells and an inconsistent emergence of T cells
      capable of killing efficiently the leukemic cells. CD1d is a restriction element
      structurally related to the major histocompatibility complex (MHC) and capable of
      presenting lipid antigens to CD1d-restricted T cells (also defined as natural
      killer-T [NKT] cells). The synthetic lipid alpha-galactosylceramide (alpha
      GalCer) has been characterized as a potent stimulator of CD1d-restricted T cells.
      We have investigated the expression of CD1d on B-CLL cells. CD1d was detected by
      flow cytometric analyses on leukemic cells of all B-CLL cases studied (n = 38)
      and was expressed at higher density on cells carrying unmutated immunoglobulin
      variable region (IgV) genes. In addition, CD1d on B-CLL cells mediated the
      presentation of alpha-GalCer to CD1d-restricted T cells, which in turn induced B
      CLL cell death. At variance with another study (Metelitsa et al., Leukemia
      2003;17:1068-77), no correlation between expression levels of CD1d and
      susceptibility to NKT cell lysis was observed. Proliferation and production of
      interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) by CD1d
      restricted T cells, in the presence of B-CLL cells loaded with alpha-GalCer, were
      also observed. Our study demonstrates that B-CLL cells express a monomorphic
      restriction element that is functionally capable of antigen presentation and can
      be useful to design novel B-CLL immunotherapies.

PMID- 14961580
TI  - Elevated hTERT mRNA levels: A potential determinant of bronchial squamous cell
      carcinoma (in situ).
AB  - Expression levels of hTERT mRNA were investigated by RT-PCR in tissue specimens
      of patients with (Group A) and without (Group B) clinically overt bronchial
      carcinoma, respectively. Bronchial carcinoma (n = 9) and distant normal (n = 9)
      specimens were analyzed in Group A. The chance of carcinoma seemed to increase
      with increasing hTERT mRNA levels (OR = 6.04, 95% CI = 1.02-37). Group B was
      comprised of 21 patients who underwent autofluorescence bronchoscopy. After
      analysis of 66 bronchial biopsies the chance of prevalent carcinoma in situ or
      carcinoma increased with increasing hTERT mRNA levels (OR = 6.19, 95% CI = 1.55
      25). Variables like age, gender, smoking history, history of cancer within the
      airways or the degree of lymphocyte infiltrate in the specimens did not modify
      this relation. In 7 Group B patients in whom bronchial cancer was diagnosed
      during follow-up, biopsies taken before cancer diagnosis from both the area of
      the newly developed tumor and distantly from this area had been analyzed for
      hTERT expression. The median hTERT mRNA level in the biopsies from the area of
      future cancer was significantly higher than in biopsies taken from distant sites
      (p < 0.03). These data indicate that elevated hTERT mRNA is associated with an
      increased relative risk of prevalent and incident bronchial squamous cell
      carcinoma (in situ).

PMID- 14961581
TI  - Cervical cancer as a priority for prevention in different world regions: an
      evaluation using years of life lost.
AB  - The relative importance of cancer of the cervix among several important causes of
      mortality (from cancer and other diseases) has been evaluated by estimating the
      years of life lost (YLL) by young and middle-aged women (25-64 years old) in
      different regions of the world. The life years were weighted to reflect their
      importance to the individual and to society. On a global basis, cancer of the
      cervix is responsible for about 2% of the total (weighted) YLL, fewer than for
      other causes of mortality in this age group. However, it is the most important
      cause of YLL in Latin America and the Caribbean. It also makes the largest
      contribution to YLL from cancer in the populous regions of SubSaharan Africa and
      South-Central Asia where the actual risk of loss of life from this cause is
      higher, although overshadowed by noncancer deaths (from AIDS, TB and maternal
      conditions). The overall picture is not very sensitive to the age weighting
      function used. The fact that most of the loss of life is preventable, and that
      simple technologies have been developed that make this practicable, means that
      cervical cancer has an even higher profile from the perspective of resource
      allocation in low income settings.

PMID- 14961582
TI  - Testicular cancer and occupational exposure to polyvinyl chloride plastics: a
      case-control study.
AB  - Exposure to polyvinyl chloride (PVC) plastics as a risk factor for testicular
      cancer was investigated. In total, 981 cases who were 20-75 years old and had
      reported to the Swedish Cancer Registry during 1993-1997 were included. One
      matched control from the population registry was used. Exposure was assessed by a
      questionnaire that was supplemented over the phone. Furthermore, an occupational
      hygienist qualified all exposures. In all, 791 matched pairs completed the
      questionnaire. Overall exposure to PVC plastics gave the odds ratio (OR)=1.35,
      95% confidence interval (CI)=1.06-1.71, increasing with >10 year latency period
      to OR=1.45, 95% CI=1.06-1.98. No dose-response relationships were found but
      rather an inverse relationship with the highest odds ratios in the lowest
      exposure category. In conclusion, no clear association with testicular cancer and
      exposure to PVC could be found in our study in contrast to a previous
      observation.

PMID- 14961583
TI  - Familial association of histology specific breast cancers with cancers at other
      sites.
AB  - Breast cancer histologies show important differences in their incidence pattern,
      method of detection and management. Aggregation of breast cancer occurs also in
      families diagnosed for cancer at sites different from the breast. Therefore, the
      familial association of histology specific breast cancers with cancers at other
      sites is of great interest. The nationwide Swedish Family-Cancer Database was
      used to calculate standardised incidence ratios (SIRs) for breast cancer when
      parents or sibling were diagnosed with cancer at the most common sites.
      Significant SIRs were found when parents had breast, ovarian, laryngeal,
      endometrial, prostate, lung and colon cancers. If women were diagnosed before the
      age of 50 years, the SIRs were significant when parents were diagnosed with
      breast, ovarian, and prostate cancers, and leukaemia, and when siblings were
      diagnosed with squamous cell skin, pancreatic, breast and endometrial cancers. If
      mothers were diagnosed with breast cancer, histology-specific SIRs were ranked as
      comedo > tubular > ductal > lobular; SIR for medullary carcinoma was not
      significant but it was high when mothers presented with ovarian cancer. Other
      associations were between the upper aerodigestive tract and lobular, colon and
      comedo, larynx and ductal cancer. Moreover, cervical cancer was associated with
      comedo and endometrial cancer with the medullary histology. In conclusion,
      histology-specific breast cancers were associated with specific cancer sites and
      the strength of the association varied among histologies.

PMID- 14961584
TI  - Perfusion of 99Tcm-labeled CD105 Mab into kidneys from patients with renal
      carcinoma suggests that CD105 is a promising vascular target.
AB  - There is strong published and unpublished evidence that our CD105 Mab E9, which
      is highly reactive with angiogenic endothelial cells, could be a useful reagent
      to target the vasculature of solid tumors in man. Since Mab E9 does not cross
      react with animal tissues, we undertook here to evaluate its localization using
      human kidney as an ex vivo model. Perfusion was performed through the renal
      artery of 99Tcm-labeled purified CD105 Mab in freshly excised kidneys from 7
      patients with renal carcinoma. In all 7 cases, immunoscintigraphs showed the
      presence of well-defined radioactive hot spots, which matched the positions of
      the tumors as identified by presurgery MRI scans and subsequent histopathologic
      examination. Importantly, in one instance, where a presurgery MRI scan had
      identified only one tumor, immunoscintigraphs showed 2 distinct hot spots of
      radioactivity. The pathology report confirmed that the additional hot spot
      corresponded to a small secondary well-vascularized tumor. The implication of
      this finding is that the radiolabeled Mab, E9, may be of use in the detection of
      metastatic disease. That the labeling of tumors was specific was confirmed when
      prior perfusion of unlabeled mab E9 in 2 kidneys completely blocked the
      localization of 99Tcm-conjugated Mab E9. Radioactivity in samples of tumor and
      normal tissue taken from 7 kidneys was counted in a gamma counter. In all cases,
      there was a greater uptake of radioactivity in tumors compared with the
      corresponding normal kidneys. The median values, adjusted per gram wet weight,
      for 99Tcm were 14.8 times (range, 4.8-113.0) greater in kidney tumors than in
      normal kidney tissue (p < 0.007). Immunofluorescent staining of cryostat sections
      of tumor tissues in each of the 7 cases showed strong and uniform localization of
      Mab E9 in tumor microvessels. Interestingly, chimeric staining of endothelial
      cells (ECs) was seen in an occasional microvessel segment. That is, while most of
      the ECs lining a microvessel were strongly stained, an occasional EC was
      negative. This was not an artifact of staining. Unstained ECs may be
      nonangiogenic or apoptotic since CD105 is a proliferation/activation-associated
      antigen. Further investigations are warranted to establish the pharmacokinetics
      of 99Tcm-labeled CD105 antibody in vivo. This would enable us to determine
      whether an apparently highly successful ex vivo study has the potential for tumor
      imaging/therapeutic vascular targeting in patients with cancer.

PMID- 14961585
TI  - Tumor necrosis factor-alpha augmented tumor response in B16BL6 melanoma-bearing
      mice treated with stealth liposomal doxorubicin (Doxil) correlates with altered
      Doxil pharmacokinetics.
AB  - The application of tumor necrosis factor-alpha (TNF) for the treatment of solid
      tumors is limited by its severe, life-threatening, toxicity. Therefore, only low
      dosages of this cytokine can be applied systemically, which results in poor tumor
      response. It has been demonstrated previously that administration of high-dose
      TNF in a so-called isolated perfusion system markedly improved tumor response
      when combined with chemotherapy. It appeared that TNF had a major impact
      specifically on the tumor-associated vasculature. At these high concentrations,
      endothelial cell death is induced by TNF, resulting in complete collapse of the
      tumor vascular bed. Strikingly, this effect alone is not enough to induce a tumor
      response, but addition of a chemotherapeutic drug is mandatory to obtain an anti
      tumor effect. We showed that TNF has no anti-tumor effect by itself but augmented
      drug accumulation mainly in the tumor, most likely by enhancing vascular leakage.
      It seems that enhanced vascular leakage, but not endothelial cell death, explains
      the interaction between TNF and the co-administered drug. We hypothesized that in
      a low-dose setting TNF could induce tumor accumulation of chemotherapeutic drugs
      and consequently improve tumor response. We demonstrate that free TNF has a
      strong effect on the pharmacokinetics of co-administered Doxil in B16BL6 melanoma
      bearing mice, resulting in strongly augmented drug accumulation in the tumor and
      improved tumor response. Co-injection of Stealth liposomal TNF with Doxil
      resulted in comparable or less pronounced tumor responses as compared to free
      TNF. These results imply that systemic application of clinically tolerable doses
      of TNF may improve drug distribution and tumor response and could be useful in a
      number of anti-cancer therapies.

PMID- 14961586
TI  - Enhanced radiosensitivity of rat autochthonous mammary tumors by dietary
      docosahexaenoic acid.
AB  - Dietary docosahexaenoic acid (DHA), which integrates into tumor cell membranes,
      has been reported to enhance the efficacy against tumors of cytotoxic drugs that
      induce reactive oxygen species (ROS). Because ionizing radiation also generate
      ROS, we initiated a study to determine whether dietary DHA might sensitize
      mammary tumors to irradiation. Mammary tumors were induced by N-methylnitrosourea
      (NMU) in Sprague-Dawley rats. The optimal dose of radiation to examine the effect
      of DHA on tumor response to irradiation was determined to be 18 grays (Gy) using
      a 4-6 MeV electron beam (according to the depth of the target volume) delivered
      in a single fraction from a linear accelerator. Two groups of rats were fed a
      basal diet containing 7% of a mixture of peanut and rapeseed oils enriched with
      8% of an oil containing either a low (palm oil) or high (DHASCO oil containing
      40% DHA) DHA content. DHA group was equally subdivided into 2 groups without or
      with addition of vitamin E (100 IU/kg diet). Irradiation was carried out when the
      first tumor in each rat reached 1.5 cm2 and subsequent change in tumor size was
      documented over time. DHA level in adipose tissue, taken as a biomarker, was
      higher in the DHA supplemented group compared to the control group. Vitamin E
      level in liver, the best storage for this compound, was higher in the vitamin E
      supplemented DHA group compared to the DHA group. Tumor size decreased by 60% at
      12 days after irradiation in the DHA group vs. 31% in the control group (p =
      0.03) and 36% in the DHA plus vitamin E group. Therefore, dietary DHA sensitized
      mammary tumors to radiation. The addition of vitamin E inhibited the beneficial
      effect of DHA, suggesting that this effect might be mediated by oxidative damage
      to the peroxidizable lipids.

PMID- 14961587
TI  - Cumulative probability of PSA increase above 4.0 NG/ML in population-based
      screening for prostate cancer.
AB  - Routine screening for prostate cancer remains controversial. However, it is very
      important to show how the optimal rescreening interval should be set for men who
      want to be screened after informed consent. To solve this issue, the risk of
      prostate-specific antigen (PSA) increase above 4.0 ng/ml relative to baseline PSA
      levels and age was investigated. Between 1988 and 2000, 7,757 subjects screened
      twice or more and also with baseline PSA levels of 4.0 ng/ml or lower were
      enrolled in our study. All serum PSA levels were measured by E-test Tosoh II PA
      assay at one center. Interval PSA levels for men undergoing screening with a
      greater than 1 year interval were calculated on the assumption that PSA levels
      changed over time in a simple exponential fashion. Then, the cumulative rate of
      freedom from PSA increase above 4.0 ng/ml was estimated using the Kaplan-Meier
      technique stratified by baseline PSA ranges of 0.0 to 1.0, 1.1 to 2.0, 2.1 to 3.0
      and 3.1 to 4.0 ng/ml and every 10 years of age ranges. Of the 7,757 subjects, 559
      (7.2%) were expected to have had PSA levels increase above 4.0 ng/ml within 5
      years after the baseline PSA measurements. The cumulative rate of freedom from
      the PSA increase above 4.0 ng/ml at 5 years was 98.7%, 92.9%, 70.3% and 38.5% in
      cases of baseline PSA levels of 1.0 ng/ml or lower, 1.1 to 2.0 ng/ml, 2.1 to 3.0
      ng/ml and 3.1 to 4.0 ng/ml, respectively. The cumulative rates of freedom from
      the PSA increase were significantly decreased with the baseline PSA ranges being
      higher regardless of age range. Re-screening interval should be set stratified by
      baseline PSA levels, regardless of age and race. Rescreening interval should be
      set at 1, 1 to 2 and 3 to 5 years for men with baseline PSA ranges of 2.1 to 4.0
      ng/ml, 1.1 to 2.0 ng/ml and 0.0 to 1.0 ng/ml, respectively, in individual-based
      screening. In mass screening system using PSA alone, rescreening interval should
      be set in the same manner as in individual-based screening, except for men with
      baseline PSA levels of 1.1 to 2.0 ng/ml, which should be set at 1 year to avoid
      developing incurable prostate cancer.

PMID- 14961588
TI  - Initial results from a randomized trial of cervical visual screening in rural
      south India.
AB  - The impact of a single round of screening of visual inspection with acetic acid
      (VIA) on cervical cancer incidence and mortality was investigated in a cluster
      randomized trial in south India. Women 30-59 years of age in 113 clusters in
      Dindigul District were randomized to VIA screening (57 clusters, 48,225 women) by
      nurses and to a control group (56 clusters, 30,167 women). 30,577 eligible women
      were screened between May 2000 and April 2003; 2,939 (9.6%) screen-positive women
      were investigated with colposcopy by nurses and 2,777 (9.1%) women had biopsy.
      CIN 1 was diagnosed in 1,778 women, CIN 2-3 lesions were found in 222, and there
      were 69 screen detected invasive cervical cancers. The detection rates of lesions
      per 1,000 screened women were 58.2 for CIN 1, 7.3 for CIN 2-3, and 2.3 for
      invasive cancer. The detection rate of high-grade lesions in our study was 2-3
      fold higher than those observed in repeatedly screened populations in developed
      countries. 71% of women with CIN 1 and 80% of those with CIN 2-3 lesions accepted
      cryotherapy provided by nurses and surgical treatment by mid-level clinicians.
      Overall, 97 and 34 incident cervical cancer cases were observed in the
      intervention and control arms, respectively. The intervention arm accrued 124,144
      person years and the control arm accrued 90,172 during the study period. The age
      standardized cervical cancer incidence rates were 92.4/100,000 person-years in
      the intervention and 43.1/100,000 in the control arms. In the screened arm, 35.0%
      of cases were in Stage I as opposed to none in the control arm. The preliminary
      findings from our study indicate that not only is a VIA-based screening programme
      feasible, safe and acceptable to a population in rural settings, it also results
      in early detection of cervical neoplasia.

PMID- 14961589
TI  - Survival after adjuvant 5-FU treatment for stage III colon cancer in hereditary
      nonpolyposis colorectal cancer.
AB  - In vitro studies suggest that a deficient mismatch repair (MMR) system reduces 5
      Fluorouracil cytotoxicity. Colon cancer (CC) in hereditary nonpolyposis
      colorectal cancer (HNPCC) is due to a dysfunctioning MMR gene that leads to
      microsatellite instability (MSI). Clinical studies on the efficacy of 5
      Fluorouracil (5-FU) in MSI high tumours are contradictory. In a retrospective
      study, we compared the survival of subjects with stage III CC from HNPCC families
      that were treated with and without adjuvant 5-FU. The Dutch HNPCC family registry
      was used. Information on adjuvant chemotherapy for stage III CC was obtained from
      subjects of families with a mutation and/or who fulfilled the AMS criteria or who
      were strongly suspicious for HNPCC. CC specific survival was calculated.
      Observation time was measured either until the date of death, date of a second
      primary CC or until the closing date of the study, i.e., June 1, 2001.
      Statistical analysis was done by Kaplan-Meier survival analysis. A total of 92
      subjects with stage III CC were included. Twenty-eight of them (17 males) had
      adjuvant treatment with 5-FU. The median follow-up was 4 (range: 1-17) years; 8
      subjects died of CC. The 5-year survival was 70% (95% Cl: 49-90). Sixty-four
      subjects (36 males) did not have adjuvant therapy. Their median follow-up was 6
      (range: 0-23) years. Twenty of them died of CC. The 5-year survival in this group
      was also 70% (95% Cl: 59-83). To date, the selection of patients with CC for 5-FU
      treatment is based on the stage rather than the biology of the tumour. In our
      study, the 5-year survival of subjects treated with and without adjuvant 5-FU did
      not differ. Further studies are necessary to elucidate the role of MSI in 5-FU
      treatment of MSI-H tumours in HNPCC.

PMID- 14961590
TI  - Lack of mutation of the folliculin gene in sporadic chromophobe renal cell
      carcinoma and renal oncocytoma.
AB  - Germline mutation of the folliculin gene (BHD) at chromosome 17p11.2 is
      associated with the development of multiplex hamartomas of the hair follicles,
      chromophobe renal cell carcinomas (RCC) and renal oncocytomas (RO). We have
      analyzed the folliculin gene with sequencing for mutations and the chromosome
      17p11.2 with microsatellites for allelic changes in sporadic ROs and chromophobe
      RCCs. Allelic loss at chromosome 17 was seen in 8 of 8 chromophobe RCCs whereas
      none of the 8 RO showed alteration at this chromosomal region. Sequencing all
      exons from genomic DNA failed to disclose mutations of the folliculin gene in any
      of the tumors. We found a single nucleotide polymorphism (SNP) of G/A (nt 74) at
      the first exon in the untranslated region of the folliculin gene. We did not find
      a correlation between the SNP G/A or loss of the G allele and the expression
      level of either splice variants of the folliculin gene. Our data suggest the
      folliculin gene does not play a role in the tumorigenesis of sporadic chromophobe
      RCCs and renal oncocytomas.

PMID- 14961591
TI  - No ING1 mutations in human brain tumours but reduced expression in high
      malignancy grades of astrocytoma.
AB  - The ING1 family of proteins has been shown to have regulatory functions in
      oncogenesis, apoptosis, DNA repair and cell cycle regulation. Here we present the
      first report on LOH analysis of the ING1 locus, mutation analysis of the complete
      coding sequence including intron-exon boundaries and expression analysis of the
      different ING1 splice products and protein isoforms in primary brain tumours. No
      somatic ING1 mutations were detected. Semi-quantitative analysis revealed higher
      levels of p33ING1b RNA in benign than in malignant lesions. This correlation was
      significant in a subset of 37 astrocytic tumours WHO grades I to IV. ING1 protein
      isoforms p47ING1a, p33ING1b and p24ING1c were found to be expressed variably in
      this series. Our findings support a regulatory contribution of ING1 to the
      development or progression of brain tumours.

PMID- 14961592
TI  - E-cadherin polymorphism--160 C/A and prostate cancer.

PMID- 14961595
TI  - Environmental forensic files.

PMID- 14961596
TI  - Breast cancer takes center stage.

PMID- 14961597
TI  - Multicomponent coupling approach to (+/-)-frondosin B and a ring-expanded
      analogue.
AB  - [reaction: see text] A recently discovered multicomponent coupling reaction is
      used to give direct access to a late intermediate in the synthesis of frondosin
      B. This intermediate can also be efficiently converted to a ring-expanded
      analogue of frondosin B by sustained heating of the reaction mixture. An
      unprecedented tandem 1,7-hydrogen shift, 8pi-electrocyclization is proposed to
      explain the formation of this ring-expanded species.

PMID- 14961598
TI  - Synthesis, modeling, and anti-tubulin activity of a D-seco paclitaxel analogue.
AB  - [reaction: see text] We have previously described a model of paclitaxel
      microtubule binding that led to the prediction that analogues of paclitaxel
      lacking any D ring could stabilize microtubules as well as paclitaxel if the
      substituent present at C4 did not have unfavorable steric interactions with the
      binding pocket. We report the synthesis of a 4-methyl paclitaxel analogue,
      compound 1, which bears this prediction out. Compound 1 is as potent as
      paclitaxel at microtubule stabilization in vitro; however, it has only about one
      four-hundredth the cytotoxicity of paclitaxel.

PMID- 14961599
TI  - Synthesis of (+/-)-secosyrin 1 and a formal synthesis of (-)-secosyrin 1.
AB  - [reaction: see text] A short synthesis of (+/-)-secosyrin 1 is presented that
      starts from an electron-deficient furan; reductive alkylation under Birch
      conditions gives rapid access to the natural product skeleton. Two aspects of
      stereoselectivity are explored, the first being directed dihydroxylation of a
      homoallylic alcohol. Second, the facial selectivity obtained during reduction of
      a highly substituted cyclic ketone was examined. Finally, our synthesis was
      rendered enantioselective by the reduction of a furan bearing a chiral auxiliary.

PMID- 14961600
TI  - A water-soluble m-phenylene ethynylene foldamer.
AB  - [reaction: see text] A water-soluble m-phenylene ethynylene (mPE) foldamer was
      realized by appending hexaethylene glycol side chains to the backbone repeat
      unit. UV spectra of the oligomer in aqueous solutions were consistent with a
      helical conformation. The association constant of the oligomer with (-)-alpha
      pinene increased dramatically with increasing water composition, peaking at 90%
      water by volume in acetonitrile. The rate of the host/guest system's approach to
      equilibrium was found to decrease considerably with increasing water content.

PMID- 14961601
TI  - Total synthesis of novel 6-substituted lavendamycin antitumor agents.
AB  - [structure: see text] Novel 6-substituted lavendamycins have been synthesized for
      the first time. The key step in these syntheses is a Pictet-Spengler condensation
      (Scheme 1). Efficient methods for the synthesis of each compound, including a
      novel reaction for the facile introduction of alkylamino groups at the C-6
      position of the lavendamycin system, are discussed. Possible mechanisms for these
      reactions are also presented.

PMID- 14961602
TI  - Unprecedented cyclizations of calix[4]arenes with glycols under the Mitsunobu
      protocol, part 2.(1) O,O-and O,S-bridged calixarenes.
AB  - [reaction: see text] Cycloalkylations of p-tert-butylcalix[4]arene (CA) and p
      tert-butylthiacalix[4]arene (TCA) with various aliphatic glycols were performed
      under the Mitsunobu protocol using the DEAD/TPP system. CA gave 1,3-dialkylated
      diols, while C(2)-C(10) glycols gave 1,2- and 1,3-bridged calixarenes. The
      reaction of TCA with C(2) diols afforded sulfonium phenoxide betaines via O,S
      cyclization, which is the first example for the alkylation of the sulfide bridge.

PMID- 14961603
TI  - Novel functionalized trisubstituted allylboronates via Hosomi-Miyaura borylation
      of functionalized allyl acetates.
AB  - [reaction: see text] A series of novel functionalized achiral and chiral
      allylboronates have been synthesized via the nucleophilic addition of boronates
      on allyl acetates derived via vinylalumination or Baylis-Hillman reaction of
      aldehydes. These reagents, upon allylboration with aldehydes, furnish beta
      substituted-alpha-methylene-gamma-butyrolactones stereoselectively.

PMID- 14961604
TI  - Snowflake-like dendrimers via site-selective synthesis of dendrons.
AB  - [structure: see text] Snowflake-shaped dendrimers were prepared via site
      selective synthesis of dendrons, where an attachment of encapsulating dendritic
      branches and an extension of phenylacetylenic units were alternatively
      manipulated on the structure of AB(2) (diethyltriazeno for A and bromo for B)
      substituted diphenylacetylene using a combination of Suzuki and Sonogashira cross
      coupling reactions.

PMID- 14961605
TI  - 2'-deoxycytidines carrying amino and thiol functionality: synthesis and
      incorporation by Vent (exo-) polymerase.
AB  - [reaction: see text] The synthesis of 2'-deoxycytidine nucleosides bearing amino
      and thiol groups appended to the 5-position of the nucleobase via a butynyl
      linker is described. The corresponding triphosphates were then synthesized from
      the nucleoside and incorporated into oligonucleotides by Vent (exo(-)) DNA
      polymerase. The ability of Vent (exo(-)) polymerase to amplify oligonucleotides
      containing these functionalized cytidine derivatives in a polymerase chain
      reaction (PCR) was demonstrated for the amino-functionalized derivative.

PMID- 14961606
TI  - Total enantioselective synthesis of (-)-cytisine.
AB  - [reaction: see text] The first total enantiosynthesis of the biologically active
      alkaloid (-)-cytisine is reported, featuring a ruthenium-catalyzed RCM reaction
      as the key step. The approach relies on readily available cis-piperidine-3,5
      dimethanol monoacetate as the chiral building block, and it is suited for
      achieving the target compound in both enantiomeric forms.

PMID- 14961607
TI  - Synthesis of all nineteen appropriately protected chiral alpha-hydroxy acid
      equivalents of the alpha-amino acids for Boc solid-phase depsi-peptide synthesis.
AB  - [reaction: see text] The preparation of depsi-peptides, amide-to-ester
      substituted peptides used to probe the role of hydrogen bonding in protein
      folding energetics, is accomplished by replacing specific l-alpha-amino acid
      residues by their alpha-hydroxy acid counterparts in a solid-phase synthesis
      employing a t-Boc strategy. Herein we describe the efficient stereoselective
      synthesis of all 19 appropriately protected alpha-hydroxy acid equivalents of the
      l-alpha-amino acids, employing commercially available materials, expanding the
      number of available alpha-hydroxy acids from 9 to 19.

PMID- 14961608
TI  - Metalated nitriles: halogen-metal exchange with alpha-halonitriles.
AB  - [reaction: see text] Alpha-halonitriles react with organometallic reagents in a
      facile halogen-metal exchange. The halogen-metal exchange is extremely fast with
      Grignard and alkyllithium reagents, generating metalated nitriles in situ with
      aldehyde, ketone, acid chloride, and acyl cyanide electrophiles. Sequential
      halogen-metal exchange and methylation of conformationally constrained nitriles
      is highly stereoselective and consistent with a retentive alkylation of a C
      magnesiated nitrile.

PMID- 14961609
TI  - Hydrolysis of alpha- and beta-glycosides. New experimental data and modeling of
      reaction pathways.
AB  - [reaction: see text] The cyclization of oxocarbenium ion conformers 6alpha and
      6beta (from 11E and 11Z) gave only the beta-glycoside 1beta, and the addition of
      methanol to the oxocarbenium ion 3 yielded mainly the alpha-glycoside 1alpha with
      both experiments being carried out under kinetically controlled conditions.
      RHF/6.31G calculations reproduce well these experimental results and show that
      the endocyclic and the exocyclic C-O bond cleavage processes can compete in the
      hydrolysis of 1beta, whereas 1alpha gets hydrolyzed by exocyclic C-O bond
      cleavage only.

PMID- 14961610
TI  - Hydrolysis of alkenyl esters and ethers catalyzed by metal complexes.
AB  - [reaction: see text] Various kinds of transition metals catalyzed the hydrolysis
      of alkenyl esters and ethers under buffer-free, high concentration conditions
      compared to usual biocatalysts. Hydrolytic kinetic resolution of cis-2-tert
      butylcyclohexyl vinyl ether was achieved by chiral (salen)Co complexes with good
      selectivity (k(rel) = 10.0).

PMID- 14961611
TI  - Synthesis of a new class of conformationally rigid phosphino-oxazolines: highly
      enantioselective ligands for Ir-catalyzed asymmetric hydrogenation.
AB  - [reaction: see text] A new class of conformationally rigid phosphino-oxazoline
      ligands were synthesized from readily available enantiopure phenyl glycinol. Ir
      complexes with these ligands are air-stable and highly enantioselective catalysts
      for asymmetric hydrogenation of aryl alkenes and alpha,beta-unsaturated esters in
      up to 99% ee.

PMID- 14961612
TI  - Thiazole orange-peptide conjugates: sensitivity of DNA binding to chemical
      structure.
AB  - [structure: see text] Derivatives of the highly fluorescent and DNA-binding dye
      thiazole orange (TO) are described that feature appended peptides.
      Functionalization of TO can be achieved at either of the endocyclic nitrogens,
      and the photophysical properties and DNA-binding modes are sensitive to the
      position of the tethered peptide. A series of TO-peptide conjugates are
      described, demonstrating the utility of a solid-phase synthesis approach to their
      preparation and illustrating how the photophysical and DNA-binding properties of
      the compounds are influenced by chemical structure.

PMID- 14961613
TI  - Ruthenium complexes as protein kinase inhibitors.
AB  - [reaction: see text] Replacing complex natural products with simple metal
      complexes could lead to a new class of metallopharmaceuticals in which the metal
      center plays mainly a structural role. A strategy is introduced for the creation
      of ruthenium complex-based protein kinase inhibitors 1 (X = CO or CH(2)), morphed
      out of the class of indolocarbazole inhibitors with the alkaloid staurosporine as
      its most prominent member.

PMID- 14961614
TI  - A convergent synthesis of the macrocyclic core of cytotrienins: application of
      RCM for macrocyclization.
AB  - [reaction: see text] The asymmetric synthesis of the fully elaborated macrocyclic
      core of cytotrienins A-D, potent apoptosis-inducing agents, is described.
      Synthetic highlights include the construction of the aniline bond using a copper
      mediated amidation and the use of a ring-closing metathesis (RCM) reaction to
      efficiently install the (E,E,E)-triene and simultaneously construct the
      macrocyclic lactam.

PMID- 14961615
TI  - Stereoselective S N 2-substitutions using polyfunctional lithium arylcuprates
      prepared by an iodine-copper exchange.
AB  - [reaction: see text] Polyfunctional mixed lithium arylcuprates of the type (FG
      Ar)(PhMe(2)CCH(2))CuLi obtained via iodine- or bromine-copper exchange with
      (PhMe(2)CCH(2))(2)CuLi react with cyclic 2-iodoallylic acetates with high S(N)2
      selectivity. The addition of ZnBr(2) changes this selectivity and allows the
      performance of highly regioselective and enantioselective anti S(N)2'
      substitutions using open-chain allylic pentafluorobenzoates.

PMID- 14961616
TI  - Catalytic C-H functionalization driven by CO as a stoichiometric reductant:
      application to carbazole synthesis.
AB  - [reaction: see text] A palladium-catalyzed regioselective C-H bond
      functionalization driven by CO as the stoichiometric reductant is described.
      Nitrogen heterocycles, e.g., carbazoles, are accessible in good to excellent
      yields with use of palladium acetate and 70 psig of carbon monoxide at 140
      degrees C.

PMID- 14961617
TI  - Total synthesis of (+)-acanthodoral by the use of a Pd-catalyzed metal-ene
      reaction and a nonreductive 5-exo-acyl radical cyclization.
AB  - [reaction: see text] The first total synthesis of the antibiotic acanthodoral (1)
      has been achieved from 3-methyl-2-cyclohexen-1-one in 19 steps in 2.1% overall
      yield. The synthesis features the use of a Pd-ene reaction in the presence of CO
      to form the endocyclic alkene 8, a nonreductive acyl radical cyclization
      reaction, and a ring contraction reaction by the Wolff rearrangement. (+)
      Acanthodoral has also been synthesized starting from (+)-S-2,2-dimethyl-6
      methylenecyclohexanecarboxylic acid.

PMID- 14961618
TI  - A general, selective, high-yield N-demethylation procedure for tertiary amines by
      solid reagents in a convenient column chromatography-like setup.
AB  - [reaction: see text] A traditional preparative chromatographic column can be used
      to achieve quantitative N-demethylation of tertiary N-methylamines and alkaloids.
      The filling is the crucial part and is loaded with different solid reagents in
      three reaction zones. The parent compound is charged on the column, and the neat
      N-demethylated secondary amine leaves the column some minutes later.

PMID- 14961619
TI  - Efficient medium-ring cyclization under non-high-dilution conditions using SmI 2.
AB  - [reaction: see text] A general, efficient, and experimentally simple method for
      generating medium rings utilizing the SmI(2)-mediated Barbier-type coupling has
      been developed. Various eight- and nine-membered carbocycles and heterocycles are
      assembled with high efficiency via this protocol. Amazingly, the process does not
      require high-dilution conditions and almost quantitative yields of the frequently
      inaccessible medium-sized rings are obtained.

PMID- 14961620
TI  - Carbaporphyrinoid chemistry has a silver lining! silver(III) oxybenzi-,
      oxynaphthi-, tropi-, and benzocarbaporphyrins.
AB  - [structure: see text] Carbaporphyrinoid systems with semiquinone,
      cycloheptatriene, or indene subunits react under mild conditions with silver(I)
      acetate to give stable silver(III) organometallic derivatives.

PMID- 14961621
TI  - First total synthesis of antimitotic compound, (+)-phomopsidin.
AB  - [reaction: see text] The first total synthesis of (+)-phomopsidin has been
      achieved via a diastereoselective transannular Diels-Alder (TADA) reaction. Key
      steps in the synthesis include diastereoselective ynone reduction with (-)-alpha
      pinene and 9-BBN, macrocyclization by E-selective intramolecular Horner-Wadsworth
      Emmons (HWE) reaction, as well as carbometalation under Wipf's conditions,
      followed by HWE reaction at low temperature to selectively construct the (E)-1
      methylpropenyl and (1E,2E)-4-carboxy-1,3-butadienyl substituents.

PMID- 14961622
TI  - Biocidal activity of polystyrenes that are cationic by virtue of protonation.
AB  - [structure: see text] Poly(1) kills bacteria (Gram-positive and -negative) and
      lyses human erythrocytes; this biocidal profile is similar to that of the peptide
      toxin mellitin. Poly(1) has antibacterial activity comparable to that of a potent
      derivative of the host defense peptide magainin II, but lacks magainin's
      selectivity for bacteria over erythrocytes. An analogous N-quaternized polymer,
      poly(3), is less biocidal than poly(1), suggesting that reversible N-protonation
      leads to greater biocidal activity than does irreversible N-quaternization.

PMID- 14961623
TI  - Benzo[d]-1,2-oxaphospholes as precursors of stabilized C-centered radicals.
AB  - [reaction: see text] Several benzo[d]-1,2-oxaphosphole 2-oxides were examined as
      potential precursors of stabilized C-centered radicals. The transient absorption
      spectra obtained after laser flash photolysis in the presence of di-tert-butyl
      peroxide showed the features of benzylic radicals with formation and decay
      kinetics not significantly influenced by the presence of oxygen. In the case of
      compounds with two possible diastereomeric forms, the C-H bond of the trans
      isomers [corrected] is more reactive toward hydrogen abstraction.

PMID- 14961624
TI  - Stereoselective intramolecular nicholas reaction using epoxides as nucleophiles.
AB  - [reaction: see text] The intramolecular nucleophilic attack of the epoxides on
      the exo-Co(2)(CO)(6)-propargylic cations provided cyclic ethers in good yields.
      The use of substrates with stereochemically defined oxiranes provided
      polysubstituted tetrahydropyrans and oxepanes with a high degree of
      stereocontrol. The cyclization is sensitive to the nature of the protecting group
      used at the primary alcohol, the use of tert-butyl carbonates being highly
      effective in terms of regioselectivity and yields.

PMID- 14961625
TI  - Synthesis of the C16-C35 fragment of integramycin using olefin
      hydroesterification as a linchpin reaction.
AB  - [reaction: see text] The spiroketal unit of the HIV-integrase inhibitor
      integramycin has been prepared in an efficient and convergent manner. Key steps
      in this sequence include the use of ruthenium-mediated hydroesterification
      reactions of homoallylic alcohols and silyl ethers, and a C,O-dianionic addition
      into a lactone provides the spiroketal while minimizing protecting group
      manipulations.

PMID- 14961626
TI  - Stereoselective carbon-carbon bond formation via the Mitsunobu displacement of
      chiral secondary benzylic alcohols.
AB  - [reaction: see text] The stereoselective displacement of a variety of chiral
      benzylic alcohols with triethylmethanetricarboxylate (TEMT) under Mitsunobu
      conditions (DEAD, PMe(3)) has been demonstrated to proceed in good yield (70-94%)
      and with a high degree of inversion. Subsequent saponification and
      decarboxylation of the products thus obtained provide chiral 3-aryl-3-substituted
      propanoic acids without racemization.

PMID- 14961627
TI  - Divergent and stereocontrolled synthesis of the enamide side chains of oximidines
      I/II/III, salicylihalamides A/B, lobatamides A/D, and CJ-12,950.
AB  - [reaction: see text] A unified strategy for the divergent and stereocontrolled
      introduction of the (E)- and (Z)-enamide side-chains of oximidines I, II, and
      III, salicylihalamides A and B, lobatamides A and D, and CJ-12,950 is detailed.
      The synthesis relied on the copper-promoted C-N coupling of (E)- and (Z)-vinyl
      iodides with a protected maleimide hemiaminal followed by deprotection and
      reaction of the resulting (E)- or (Z)-enelactam hemiaminals with O
      methylhydroxylamine or propylidenetriphenylphosphorane.

PMID- 14961628
TI  - Ru(III)-catalyzed cyclization of arene-alkene substrates via intramolecular
      electrophilic hydroarylation.
AB  - [reaction: see text] We herein report that RuCl(3)/AgOTf has proven to be a
      hydroarylation catalyst with an efficiency and scope superior to previously known
      methods. This catalyst demonstrated consistent performance with arene-ene
      substrates of diverse structural features, providing good to excellent yields of
      cyclization products (chromanes, tetralins, terpenoids, dihydrocoumarins).

PMID- 14961629
TI  - Regioselective glycosylation of neamine core: a facile entry to kanamycin B
      related analogues.
AB  - [reaction: see text] Introduction of a sugar unit at either the O5 or O6 position
      of various neamine derivatives in excellent selectivity and yields is described
      here. Application to the synthesis of kanamycin analogues is also highlighted.

PMID- 14961630
TI  - [N]Chalcogena[N]pericyclynes: DFT studies on binaric carbon-chalcogen compounds.
AB  - [structure: see text] DFT studies on [N]chalcogena[N]pericyclynes (n = 3-6, 8)
      demonstrate their relative stability and hence their possible existence as stable
      species. By minimizing repulsive interactions between the chalcogens' lone pairs,
      the molecules adopt structures that resemble, in shape, cycloalkanes or elemental
      chalcogens. [3]Chalcogena[3]pericyclynes may be interconverted with their valence
      tautomers, benzene derivatives with three fused three-membered rings.

PMID- 14961631
TI  - Triethylborane-induced radical allylation reaction with zirconocene-olefin
      complex.
AB  - [reaction: see text] Allylzirconium reagents are effective for radical allylation
      of alpha-halo carbonyl compounds. The key steps would be homolytic cleavage of
      the zirconium-carbon bond and halogen abstraction by the resulting
      Cp(2)ZrCl(III). Zirconocene-olefin complex can be also utilized for the
      allylation of alpha-halo compounds.

PMID- 14961632
TI  - Absolute stereochemistry of ulapualide A.
AB  - [structure: see text] The structure of ulapualide A (1) has been solved by X-ray
      crystallography in a complex with G-actin. The stereochemical configuration was
      assigned as 3S,9S,22S,23R,24S,26S,27S,31R,32R,33R.

PMID- 14961633
TI  - Disulfidation of alkynes and alkenes with gallium trichloride.
AB  - [reaction: see text] Treatment of diphenyl disulfide and terminal alkynes with
      gallium trichloride afforded (E)-1,2-diphenylthio-1-alkenes selectively (E/Z >
      20/1). Alkenes also underwent this reaction to form trans adducts.

PMID- 14961634
TI  - Platinum(II)-catalyzed reaction of 2-alkynylbenzoates or benzothioates with vinyl
      ethers: a concise method for synthesis of 1-acyl-4-alkoxy- or 1-acyl-4
      alkylsulfanylnaphthalene derivatives.
AB  - [reaction: see text] A concise method for the preparation of 1-acyl-4-alkoxy- or
      1-acyl-4-alkylsulfanylnaphthalenes has been developed by the reaction of o
      ethynylbenzoates or benzothioates with vinyl ethers, in the presence of a
      catalytic amount of PtCl(2). It is proposed that the reaction proceeds through [3
      + 2]-cycloaddition of the platinum-containing carbonyl ylides followed by 1,2
      alkyl migration.

PMID- 14961635
TI  - Nucleophilic addition to electron-rich heteroaromatics: dearomatizing anionic
      cyclizations of pyrrolecarboxamides.
AB  - [reaction: see text] Despite its electron-rich nature, a pyrrole ring is
      susceptible to intramolecular nucleophilic attack by organolithiums. The
      resulting dearomatizing anionic cyclization yields new 5- or 7-membered
      heterocyclic rings. Formation of a new 5-membered ring, by cyclization of an N
      benzylpyrrolecarboxamide, is accompanied by ring opening of the original pyrrole
      to yield 3-aminovinylpyrrolinones. Formation of a new 7-membered ring, by
      cyclization of an N-allyl pyrrolecarboxamide, yields bicyclic pyrroloazepinones.

PMID- 14961636
TI  - An expeditious Nazarov cyclization strategy toward the hydroazulene core of
      guanacastepene A.
AB  - The hydroazulene core of guanacastepene A has been synthesized in five steps from
      commercially available starting materials using a classical Nazarov cyclization
      to install the stereochemistry in the cyclopentanone diastereoselectively. In the
      presence or absence of Lewis bases, a hydroazulenone or a spirocyclic ketone
      generated via a novel Wagner-Meerwein rearrangement is obtained with excellent
      selectivity and yield.

PMID- 14961637
TI  - Boron trifluoride induced palladium-catalyzed cross-coupling reaction of 1
      aryltriazenes with areneboronic acids.
AB  - [reaction: see text] Aryltriazenes are directly coupled with areneboronic acids
      in the presence of a catalytic amount of Pd(2)(dba)(3) and P(tBu)(3) together
      with 1 equiv of BF(3).OEt(2) in DME to afford the corresponding biaryl products
      in up to 98% yield. A carbonylative cross-coupling reaction under a carbon
      monoxide atmosphere is also found to give the corresponding diaryl ketone with a
      similar catalyst system.

PMID- 14961638
TI  - Alpha-sulfinyl carbanions as a new source of olefins.
AB  - [reaction: see text] Secondary alpha-lithiosulfinyl carbanions react either
      intermolecularly, after transmetalation into an organocopper derivative in an
      S(N)2-type process with zinc carbenoid, or intramolecularly via higher-order
      zincate to give, through a tandem zinc homologation-beta-elimination reaction the
      corresponding alkenes. alpha,alpha-Disubstituted alkenes are only formed from
      tertiary alpha-lithiosulfinyl carbanions via the 1,2-metalate rearrangement.

PMID- 14961639
TI  - Enantioselective aza-Henry reaction catalyzed by a bifunctional organocatalyst.
AB  - [reaction: see text] The aza-Henry reaction of imines with nitroalkanes was
      promoted by chiral thiourea with an N,N-dimethylamino group to give beta
      nitroamines with good enantioselectivity. Various N-protected imines were
      examined as substrates. N-Phosphinoylimine gave the best result in terms of
      chemical yield and enantioselectivity (up to 91% yield, up to 76% ee).

PMID- 14961640
TI  - Substituent effects on competitive release of phenols and 1,3-rearrangement in
      alpha-keto amide photochemistry.
AB  - [reaction: see text] Photolysis of alpha-keto amides bearing 4-YC(6)H(4)O leaving
      groups at the position alpha to the keto group efficiently produces high yields
      of phenols when Y is an electron-withdrawing group or H. The photoelimination
      likely involves cleavage of zwitterionic intermediates produced via excited-state
      hydrogen transfer. When Y is an electron-donating group, competing excited-state
      ArO-C(alpha) bond scission to radicals occurs, followed by recombination to give
      1,3-photorearrangment products.

PMID- 14961641
TI  - A new cucurbitacin D related 16,23-epoxy derivative and its isomerization
      products.
AB  - [reaction: see text] A new (23S,24Z)-16,23-epoxy cucurbitacin derivative was
      isolated from Ecballium elaterium L. (Cucurbitaceae) fruit juice along with known
      cucurbitacin derivatives. Structure elucidation of these derivatives was
      accomplished by NMR spectroscopy and mass spectrometry from HPLC-MS data.
      Isomerization of the epoxy derivative was monitored by 1D and 2D NMR experiments.
      The configuration of the reaction products was elucidated as (23R,24E) and
      (23R,24Z), and a mechanism for the acid-catalyzed rearrangement process is
      proposed.

PMID- 14961642
TI  - Trifluoroacetyl-activated nitrogen-nitrogen bond cleavage of hydrazines by
      samarium(II) iodide.
AB  - [reaction: see text] Trifluoroacetyl derivatives of hydrazines undergo clean and
      efficient reductive cleavage of the N-N bond with SmI(2) in the presence of MeOH.
      After N-trifluoroacetylation, acyl-, aryl-, and alkyl-substituted hydrazines are
      reductively cleaved by this method to afford trifluoroacetamides in yields
      ranging from 70 to 96%. These conditions accommodate alkene functionality, avoid
      racemization, and furnish chiral amines bearing a readily removable TFA
      protecting group.

PMID- 14961643
TI  - Oxazolidine ring opening and isomerization to (E)-imines. Asymmetric synthesis of
      aryl-alpha-fluoroalkyl amino alcohols.
AB  - [reaction: see text] A base-induced ring opening/imine
      isomerization/diastereoselective organometallic addition sequence on 4
      substituted 2-perfluoroalkyl-1,3-oxazolidines has been developed for the
      asymmetric synthesis of aryl alpha-perfluoroalkylamine derivatives. This
      practical method provides chiral amino alcohols in 60-95% yield with uniformely
      high diastereoselectivities ranging from 35:1 to >100:1.

PMID- 14961644
TI  - Total synthesis of (+/-)-herbertenolide by stereospecific formation of vicinal
      quaternary centers in a crystalline ketone.
AB  - [reaction: see text] The sesquiterpene (+/-)-herbertenolide was synthesized in
      seven steps from commercial 2-bromo-4-methylanisole. In the key step, two
      adjacent stereogenic quaternary centers were controlled by a highly
      chemoselective and stereospecific photodecarbonylation reaction of crystalline
      methyl-trans-3-(2-methyl-5-methoxyphenyl)-1,3-dimethyl-2-oxocyclohexancarboxylate
      (3). An efficient generation of radical pairs and the stereochemical control
      exerted by the solid state suggest that this reaction may become a useful
      synthetic method.

PMID- 14961647
TI  - Synthesis of oligomers derived from amide-linked neuraminic acid analogues.
AB  - N-Fluoren-9-ylmethoxycarbonyl-protected sugar amino acids derived from alpha-O
      methoxy- and 2,3-dehydroneuraminic acids have been prepared. Incorporation of
      these monomer units into solid-phase synthesis led to the efficient synthesis of
      two series of oligomers varying from one to eight units in length. The (1-->5)
      linked amides of 2,3-dehydroneuraminic acid were further subjected to
      hydrogenation giving a third series of oligomers with a beta-hydrido substituent
      at the anomeric carbon.

PMID- 14961648
TI  - Synthesis of well-defined tower-shaped 1,3,5-trisubstituted adamantanes
      incorporating a macrocyclic trilactam ring system.
AB  - We describe the synthesis of two novel well-defined tower-shaped 1,3,5
      trisubstituted adamantanes 30 and 33 that incorporate a macrocyclic trilactam
      ring system. Each nanoscale molecule has a broad tripodal base consisting of
      three identical sulfur-containing termini as the tripod feet, 4
      acetylsulfanylmethylphenyl units in the case of 30 and 3,5
      bis(acetylsulfanylmethyl)phenyl units in the case of 33. The sulfur atoms are
      designed to bind the molecules trivalently to the apex of a gold-coated
      commercial AFM tip through formation of three S-Au bonds. The rigid adamantane
      derived head unit with a single hydrogen atom at the apex is designed to scan the
      sample. Molecules 30 and 33 are synthesized from 1,3,5-triethynyladamantane by a
      series of Sonogashira coupling reactions involving terminal alkynes and aryl
      iodides. A macrocyclic trilactam unit is included for added rigidity. We
      demonstrate that molecule 30 is sufficiently large and rigid to be visualized by
      a conventional AFM tip. These nanoscale molecules may also find application as
      chemically well-defined nanoscale objects for calibration of AFM tips.

PMID- 14961649
TI  - Absolute rate constants for reactions of tributylstannyl radicals with
      bromoalkanes, episulfides, and alpha-halomethyl-episulfides, -cyclopropanes, and 
      oxiranes: new rate expressions for sulfur and bromine atom abstraction.
AB  - Arrhenius rate expressions were determined for the abstraction of bromine atom
      from 2-phenethyl bromide by tri-n-butylstannyl radical (Bu(3)Sn(*)) in benzene
      using transient absorption spectroscopy, (log(k(abs,Br)/M(-1) s(-1)) = (9.21 +/-
      0.20) - (2.23 +/- 0.28)/theta, theta = 2.3RT kcal/mol, errors are 2sigma) and for
      the abstraction of sulfur atom from propylene sulfide to form propylene,
      (log(k(s)/M(-1) s(-1)) = (8.75 +/- 0.91) - (2.35 +/-1.33)/theta). Rate constants
      for reactions of organic bromides, RBr, with Bu(3)Sn(*) were found to vary as R =
      benzyl (15.6) > thiiranylmethyl (6.2) > oxiranylmethyl (3.1) > cyclopropylmethyl
      (1.3) > 2-phenethyl (1.0), with k(abs,Br) = 6.8 x 10(7) M(-1) s(-1) at 353 K for
      2-phenethyl bromide. Bromine abstraction from alpha-bromomethylthiirane is about
      7-fold faster than sulfur atom abstraction and is comparable to the reactivity of
      a secondary alkyl bromide. The potential surface for the vinylthiomethyl -->
      allylthiyl radical rearrangement at UB3LYP/6-31G(d) and UB3LYP/6-311+G(2d,2p)
      levels of theory suggests that the thiiranylmethyl radical is produced about 9
      kcal/mol above the allylthiyl radical on the rearrangement surface, consistent
      with the observed enhancement of the Br atom abstraction from the thiirane and
      with synchronous C-S bond scission of the thiirane ring. The selectivities
      reported in this work for S vs Cl and Br abstraction provide applications for
      radical-based synthesis and new competition basis rate expressions for
      trialkylstannyl radicals.

PMID- 14961650
TI  - Synthesis of diverse macrocyclic peptidomimetics utilizing ring-closing
      metathesis and solid-phase synthesis.
AB  - The synthesis of a range of highly functionalized peptidomimetic macrocycles has
      been accomplished using ring-closing metathesis and enyne tandem cross-metathesis
      ring-closing metathesis reactions. This approach gives access to rigidified
      macrocycles modeled on the structures of cyclic peptides and designed to be
      biologically stable. The potential for peripheral functionalization of these
      templates has been demonstrated using Diels-Alder reactions, palladium(0)
      coupling reactions, and amide formation both in the solution phase and using
      polymer-supported syntheses.

PMID- 14961651
TI  - Organolanthanide-catalyzed intramolecular
      hydroamination/cyclization/bicyclization of sterically encumbered substrates.
      Scope, selectivity, and catalyst thermal stability for amine-tethered unactivated
      1,2-disubstituted alkenes.
AB  - This paper reports the organolanthanide-catalyzed intramolecular
      hydroamination/cyclization of amine-tethered unactivated 1,2-disubstituted
      alkenes to afford the corresponding mono- and disubstituted pyrrolidines and
      piperidines using coordinatively unsaturated complexes of the type (eta(5)
      Me(5)C(5))(2)LnCH(TMS)(2) (Ln = La, Sm), [Me(2)Si(eta(5)
      Me(4)C(5))(2)]SmCH(TMS)(2), and [Me(2)Si(eta(5)-Me(4)C(5))((t)BuN)]LnE(TMS)(2)
      (Ln = Sm, Y, Yb, Lu; E = N, CH) as precatalysts. [Me(2)Si(eta(5)
      Me(4)C(5))((t)BuN)]LnE(TMS)(2) mediates intramolecular hydroamination/cyclization
      of sterically demanding amino-olefins to afford disubstituted pyrrolidines in
      high diastereoselectivity (trans/cis = 16/1) and good to excellent yield. In
      addition, chiral C(1)-symmetric organolanthanide catalysts of the type
      [Me(2)Si(OHF)(CpR*)]LnN(TMS)(2) (OHF = eta(5)-octahydrofluorenyl; Cp = eta(5)
      C(5)H(3); R* = (-)-menthyl; Ln = Sm, Y), and [Me(2)Si(eta(5)
      Me(4)C(5))(CpR*)]SmN(TMS)(2) (Cp = eta(5)-H(3)C(5); R* = (-)-menthyl) mediate
      asymmetric intramolecular hydroamination/cyclization of amines bearing internal
      olefins and afford chiral 2-substituted piperidine and pyrrolidine in
      enantioselectivities as high as 84:16 er at 60 degrees C. The substrate of the
      structure NH(2)CH(2)CMe(2)CH(2)CH=CH(CH(2))(2)CH=CH(2) is regiospecifically
      bicyclized by [Me(2)Si(eta(5)-Me(4)C(5))((t)BuN)]LnE(TMS)(2) to the corresponding
      indolizidine skeleton in good yield and high diastereoselectivity. Thermolysis of
      (eta(5)-Me(5)C(5))(2)LaCH(TMS)(2) in cyclohexane-d(12) at 120 degrees C rapidly
      releases CH(2)(SiMe(3))(2) and leads to possible formation of fulvene (eta(6)
      Me(4)C(5)CH(2)-) species. The thermolysis product readily reverts to active
      catalysts upon protonolysis by substrate and exhibits the same catalytic activity
      as the (eta(5),eta(1)-Me(5)C(5))(2)LaCH(TMS)(2) precatalyst at 120 degrees C in
      the cyclization of cis-2,2-dimethylhept-5-enylamine. Catalytically-active
      lanthanide-amido complexes (eta(5)-Me(5)C(5))(2)La(NHR)(NH(2)R)(n) and
      [Me(2)Si(eta(5)-Me(4)C(5))((t)BuN)]Sm(NHR)(NH(2)R)(n) are shown to be thermally
      robust species.

PMID- 14961652
TI  - Anodic oxidation of mono- and disubstituted 1,4-dimethoxybenzenes.
AB  - The electrochemical oxidation of mono- and disubstituted 1,4-dimethoxybenzene
      derivatives with zero, one, and two benzylic CH(2)X groups (X = OAc, Cl, OH) (5a
      c and 6a-c) has been carried out by using both constant-current and controlled
      potential techniques in methanol and in the presence of different electrolytes
      and working electrodes. Constant-current electrolysis in KOH-methanol solutions
      yielded mostly the corresponding 1,4-quinone derivatives from 5a-c and 6b,
      whereas the disubstituted 1,4-dimethoxybenzenes 6a,c underwent side-chain
      oxidation to form 2,5-dimethoxyterephthalaldehydes. Upon alteration of the medium
      from the commonly used basic KOH-methanol to neutral LiClO(4)-methanol, a new
      spectrum of products was achieved in most cases, involving novel coupling
      products from monosubstituted substrates and quinone derivatives from
      disubstituted ones. Controlled-potential oxidation at the glassy carbon anodes
      and in a neutral LiClO(4)-methanol medium led to more complex mixtures of
      products, namely, polymers and new coupling products from monosubstituted
      substrates and quinones and side-chain oxidation (or substitution) products from
      the disubstituted ones. Three new coupling products were isolated and
      characterized by X-ray measurements.

PMID- 14961653
TI  - Blockwise approach to fragments of the O-specific polysaccharide of Shigella
      flexneri serotype 2a: convergent Synthesis of a decasaccharide representative of
      a dimer of the branched repeating unit.
AB  - The D'A'B'(E')C'DAB(E)C decasaccharide representative of a dimer of a frame
      shifted pentasaccharide repeating unit of the O-specific polysaccharide of
      Shigella flexneri 2a was synthesized as its methyl glycoside by condensing a
      pentasaccharide donor (D'A'B'(E')C') and a pentasaccharide acceptor (DAB(E)C
      OMe). Several convergent routes to these two building blocks, involving either
      the AB linkage or the BC linkage as the disconnection site, were evaluated in
      comparison to the linear strategy. The latter was preferred. It is based on the
      use of the trichloroacetimidate chemistry. The target branched oligosaccharide
      was designed to probe the recognition at the molecular level of the natural
      polysaccharide by protective monoclonal antibodies.

PMID- 14961654
TI  - Insight into the reactivity of olefins in the Pauson-Khand reaction.
AB  - The reactivity of different Co(2)(CO)(6)-acetylene complexes in the Pauson-Khand
      reaction is strongly dependent on the nature of the olefin. Theoretical
      calculations at both the DFT and ONIOM levels are concordant with experimental
      observations and suggest how the olefin-cobalt interactions in the complex could
      have a major effect on the relative reactivity of the olefins. This study
      rationalizes for the first time the experimentally observed reactivity
      differences of cyclohexene, cyclopentene, and norbornene.

PMID- 14961655
TI  - Glycosylthiomethyl chloride: a new species for S-neoglycoconjugate synthesis.
      Synthesis of 1-N-glycosylthiomethyl-1,2,3-triazoles.
AB  - Reaction of O-acyl-protected glycosylthiols with dichloromethane afforded readily
      glycosylthiomethyl chlorides, which gave with sodium azide the corresponding
      glycosylthiomethyl azides 17-22. Reaction of these azides with dicyclopentadiene
      as dipolarophile led to tandem 1,3-dipolar cycloaddition/retro-Diels-Alder
      reaction furnishing the parent 1-glycosylthiomethyl-1,2,3-triazoles 23-25.
      Reaction of azides with acetylene derivatives gave directly 1-glycosylthiomethyl
      1,2,3-triazoles which are ring-substituted.

PMID- 14961656
TI  - NMR chemical shifts. Substituted acetylenes.
AB  - The MPW1PW91/6-311+G(2d,p) and MP2/6-311+G(2d,p) GIAO nuclear shieldings for a
      series of monosubstituted acetylenes have been calculated using the MP2/6
      311G(2d,p) geometries. Axially symmetric substituents such as fluorine may lead
      to large changes in the isotropic shielding but have little effect on the tensor
      component (zz) about the C[triple bond]C bond axis. On the other hand,
      substituents such as vinyl and aldehyde groups lead to essentially no difference
      in the isotropic shielding but are calculated to give a large zz paramagnetic
      shift to the terminal carbon of the acetylene group, without having much effect
      on the inner carbon. The tensor components of the chemical shifts for
      trimethylsilylacetylene, methoxyacetylene, and propiolaldehyde have been measured
      and are in reasonable agreement with the calculations. The downfield shift at the
      terminal carbon of propiolaldehyde along with a small upfield shift at the
      adjacent carbon has been found to result from the coupling of the in-plane pi MO
      of the acetylene with the pi* orbital that has a node near the central carbon.
      The tensor components for acetonitrile also have been measured, and the shielding
      of cyano and acetylenic carbons are compared.

PMID- 14961657
TI  - Accelerated Koenigs-Knorr glucuronidation of a deactivated nitrophenol: unveiling
      the role of polyamine additive 1,1,4,7,10,10-hexamethyltriethylenetetramine
      through design of experiments.
AB  - 1,1,4,7,10,10-Hexamethyltriethylenetetramine (HMTTA) emerged from a limited
      parallel screening of selected polyamines as the most appropriate additive for an
      especially problematic Koenigs-Knorr glucuronidation. This initial finding
      rapidly evolved into a reliable and high-yielding procedure through the use of
      two sets of experimental designs. The detailed effect of the stoichiometry of
      reagents and the amount of amine additive on reaction yield was elucidated. The
      complexity of the response surface for product yield, described by a third-order
      polynomial equation, together with ancillary kinetic experiments evidenced the
      multiple role of HMTTA in the present glucuronidation process.

PMID- 14961658
TI  - N-(17-Phosphonooxylinolenoyl)glutamine and N-(17-phosphonooxylinoleoyl)glutamine
      from insect gut: the first backbone-phosphorylated fatty acid derivatives in
      nature.
AB  - N-(17-Phosphonooxylinolenoyl)glutamine (1) and N-(17
      phosphonooxylinoleoyl)glutamine (2) were isolated from the regurgitate of
      Spodoptora exigua and identified as the first natural alkyl chain-phosphorylated
      fatty acid derivatives. The compounds were characterized by HPLC-MS/MS and the
      assigned structures confirmed by synthesis via a dissymmetric bis-Wittig approach
      as the key reaction. Rearing of the larvae on a diet enriched with inorganic
      phosphate increased the amount of the phosphorylated N-acyl glutamines in the
      regurgitate.

PMID- 14961659
TI  - Alpha,omega-bis(thioacetyl)oligophenylenevinylene chromophores from thioanisol
      precursors.
AB  - The selective cleavage of arylmethyl thioethers provides a convenient protocol
      for the synthesis of all-E isomers of alpha, omega
      bis(thioacetyl)oligophenyenevinylene molecules (OPVs). The S-methyl group is
      tolerant of Wittig-type and Heck-type reactions for forming OPV structures and
      can be converted to the S-acetyl group by treatment with sodium thiomethoxide and
      acetyl chloride. The thermal conditions of the deprotection/reprotection step
      concurrently isomerize the conjugated chromophore to the all-E isomer, regardless
      of the stereochemistry of the starting olefins. This approach is demonstrated for
      a variety of linear and [2.2]paracyclophane containing OPVs, which have been
      characterized by electrochemical and spectroscopic techniques. Additionally,
      these S-acetyl-terminated OPVs self-assemble on gold surfaces. Monolayers
      containing these molecules were characterized by water contact angle
      measurements, ellipsometry, and X-ray photoelectron spectroscopy.

PMID- 14961660
TI  - [2 + 2]-Photocycloaddition of 1,1-diethoxyethylene to chiral polyfunctional 2
      cyclohexenones. Regioselectivity and pi-facial discrimination.
AB  - The photochemical [2 + 2]-cycloadditions of 1,1-diethoxyethylene to chiral
      polyfunctional 2-cyclohexenones have been carried out leading to the production
      of highly constrained unusual alpha-amino acids with excellent regioselectivity
      and satisfactory yields. Theoretical calculations have been done to rationalize
      the observed regio- and diastereoselectivity and show that regiochemistry is
      determined by the relative rate of formation of the 1,4-biradical intermediates
      and not by the stability of these species.

PMID- 14961661
TI  - Development of an efficient procedure for indole ring synthesis from 2
      ethynylaniline derivatives catalyzed by CuII salts and its application to natural
      product synthesis.
AB  - The development of efficient methods for the indole synthesis catalyzed by Cu(II)
      salts and its applications were investigated. Cu(OAc)(2) has been proved to be
      the best catalyst for the synthesis of various 1-p-tolylsulfonyl or 1
      methylsulfonylindoles, which have both electron-withdrawing and electron-donating
      groups on the aromatic ring and C2 position of indoles. For the primary aniline
      derivatives, Cu(OCOCF(3))(2) showed good activities, while Cu(OAc)(2) was a good
      catalyst for the cyclization of secondary anilines. This methodology could be
      applied to the sequential cyclization reaction for the compounds which have the
      electrophilic part in the same molecule. By prior treatment with KH, the
      sequential cyclization was realized to provide the tricyclic ring systems, but it
      was limited to five- and six-membered rings for the second cyclization. Finally,
      formal and total synthesis of hippadine with the Cu(II)-promoted indole synthesis
      as the key step was accomplished.

PMID- 14961662
TI  - Preparation and palladium-catalyzed cross-coupling of aryl triethylammonium
      bis(catechol) silicates with aryl triflates.
AB  - Pentavalent aryl and heteroaryl bis(catechol) silicates undergo palladium
      catalyzed cross-coupling with aryl and heteroaryl triflates in the presence of a
      fluoride source in excellent yields. These solid, air-stable bis(catechol)
      silicates are prepared from a high-yielding displacement reaction between
      catechol and an aryl siloxane in the presence of an amine base. The cross
      coupling reaction is tolerant of a wide range of electron-donating and electron
      withdrawing groups. Several examples of di-ortho-substituted triflates are
      successfully coupled with these reagents.

PMID- 14961663
TI  - Double-chelation-assisted Rh-catalyzed intermolecular hydroacylation between
      salicylaldehydes and 1,4-penta- or 1,5-hexadienes.
AB  - Intermolecular hydroacylation between salicylaldehydes 1, 26-40 and 1,4-penta- or
      1,5-hexadienes 4-13 by Rh-catalyst proceeded under mild reaction conditions to
      give a mixture of iso- and normal-hydroacylated products 14-25, 41-55, and 57-60.
      In the hydroacylation reaction, chelation of both salicylaldehyde and diene to
      the Rh-complex plays a crucial role. The ratio of iso- and normal-hydroacylated
      products could be regulated by the addition of salicylic acid or amines. The
      effects of various Rh-complexes, solvents, and additives were examined, and the
      plausible mechanisms of the catalytic cycle were proposed on the basis of the
      deuterium-labeling salicylaldehyde experiments.

PMID- 14961664
TI  - Enols of amides activated by the 2,2,2-trichloroethoxycarbonyl group.
AB  - Reaction of isocyanates XNCO (X = Ar, i-Pr, t-Bu) with CH(2)(Y)CO(2)CH(2)CCl(3)
      (Y = CO(2)Me, CO(2)CH(2)CCl(3), CN) gave 15 amides XNHCOCH(Y)CO(2)CH(2)CCl(3) (6)
      or enols of amides XNHC(OH)=C(Y)CO(2)CH(2)CCl(3) (5) systems. The amide/enol
      ratios in solution depend strongly on the substituent Y and the solvent and
      mildly on the substituent X. The percentage of enol for group Y increases
      according to Y = CN > CO(2)CH(2)CCl(3) > CO(2)Me and decreases with the solvent
      according to CCl(4) > C(6)D(6) > CDCl(3) > THF-d(8) > CD(3)CN > DMSO-d(6). With
      the most acidic systems (Y = CN) amide/enol exchange is observed in moderately
      polar solvents and ionization to the conjugate base is observed in DMSO-d(6). The
      solid-state structure of the compound with Y = CN, X = i-Pr was found to be that
      of the enol. The reasons for the stability of the enols were discussed in terms
      of polar and resonance effects. Intramolecular hydrogen bonds result in a very
      low delta(OH) and contribute to the stability of the enols and are responsible
      for the higher percentage of the E-isomers when Y = CO(2)Me and the Z-isomers
      when Y = CN. The differences in delta(OH), delta(NH), K(enol), and E/Z enol
      ratios from the analogues with CF(3) instead of CCl(3) are discussed.

PMID- 14961665
TI  - Functionalized spiro- and fused-ring heterocycles via oxidative demetalation of
      cyclohexadienyl ruthenium complexes.
AB  - Electron-rich alkoxy- and chloro-substituted azaspirocyclic cyclohexadienyl
      Ru(II) complexes have been converted to either azaspiro[4.5]decane derivatives or
      functionalized tetrahydroisoquinolines by treatment with suitable oxidizing
      agents. Copper(II) chloride was found to provide demetalated products in high
      yield relative to the other oxidants examined (FeCl(3), DDQ, CAN,
      [Cp(2)Fe][PF(6)], phenyliodine diacetate, IBX). In certain instances, the
      efficiency of oxidative demetalation was enhanced by the inclusion of chloride
      ion additives in the reaction. Pyridinium dichromate (PDC) was also found to
      effect the demetalation of a wide range of cyclohexadienyl Ru complexes; however,
      isolated yields of metal-free products were exceedingly low. The cyclohexadienyl
      ruthenium complexes used in this study were prepared from (arene)Ru(II)
      precursors; thus, the isolation of alicyclic cyclohexadienone derivatives upon
      demetalation constitutes completion of a Ru-mediated dearomatization process.

PMID- 14961666
TI  - One-electron attachment reaction of B- and Z-DNA modified by 8-bromo-2'
      deoxyguanosine.
AB  - The one-electron attachment reaction of 8-bromo-2'-deoxyguanosine ((Br)G) in DNA
      was studied by comparing that in B- and Z-DNA. Oligodeoxynucleotides (ODNs)
      modified by (Br)G were synthesized as Z-DNA in which the syn-conformation
      deoxyguanosine is stabilized by steric interference between the 8-bromo group of
      (Br)G and the sugar moiety. Debromination from the (Br)G-modified ODNs occurred
      from the one-electron attachment during the gamma-radiolysis. The structural
      dependence of B- and Z-DNA was observed for the one-electron attachment reaction.
      The conversion of (Br)G was higher in Z-DNA than in B-DNA. Because the solvent
      accessible surface of the purine base in Z-DNA is greater than that in B-DNA, it
      is demonstrated that the reactivity of purine base C8 is enhanced in Z-DNA
      compared to that in B-DNA.

PMID- 14961667
TI  - Glycolipids from sponges. 13. Clarhamnoside, the first rhamnosylated alpha
      galactosylceramide from Agelas clathrodes. Improving spectral strategies for
      glycoconjugate structure determination.
AB  - Reinvestigation of the glycosphingolipid composition of the marine sponge Agelas
      clathrodes revealed the presence of a new tetraglycosylated alpha
      galactoglycosphingolipid (1a), containing an unusual l-rhamnose unit in the sugar
      head. The structure of the new compound was elucidated using extensive 2D NMR
      studies. Because of the strong overlapping of the signals of the sugar protons in
      the (1)H spectrum, (13)C-coupled and (13)C-decoupled phase-sensitive HMQC spectra
      were used to study the multiplicity of the overlapping signals. In addition, the
      absolute configuration of sugars was determined using a simple and efficient, yet
      underutilized CD method.

PMID- 14961668
TI  - Novel betaines from a micronesian sponge Dysidea herbacea.
AB  - Three new betaines, dysibetaine PP (1), dysibetaine CPa (2), and dysibetaine CPb
      (3), were isolated from an aqueous extract of the marine sponge Dysidea herbacea
      collected in Yap state, Micronesia. The structure of 1 was determined by spectral
      methods as well as chemical degradation to be a novel dipeptide betaine, and
      those for 2 and 3 were determined to be unprecedented cyclopropane betaines.
      Compounds 2 and 3 showed weak affinity toward the N-methyl-D-aspartic acid-type
      and the kainic acid-type glutamate receptors, respectively, in a radioligand
      binding assay.

PMID- 14961669
TI  - Stereochemistry of reactions involving rotationally restricted, sterically
      hindered cations, radicals, and anions: 9-fluorenyl systems.
AB  - A study of the stereochemical pathways of reactions involving rotationally
      restricted, sterically hindered cations, radicals, and anions has been undertaken
      utilizing chiral 9-(o-tert-butylphenyl)fluorenes. Previous reports of studies
      with these or related achiral compounds contained erroneous or equivocal
      conclusions. This study shows that (+)-sp-9-(o-tert-butylphenyl)-9-methoxy-2
      methylfluorene, treated with Tf(2)O-CHCl(3) to form 100% of the 9-cation, then
      with NaOMe-MeOH, provided 29% of re-formed substrate (configurational retention)
      and 71% of the (-)-sp enantiomer (inversion). The same substrate treated with HI
      CHCl(3) was converted into the 9-radical, which was rapidly reduced, affording
      100% isolation of (-)-sp-9-(o-tert-butylphenyl)-2-methylfluorene (inversion).
      Treatment of the latter with n-BuLi-THF provided the 9-anion which, on
      acidification, yielded 100% of the enantiomeric (+)-sp-9-(o-tert-butylphenyl)-2
      methylfluorene (inversion). The substrates in these reactions were the
      thermodynamically favored sp rotamers. Inversion directly produced the higher
      energy nonenantiomeric ap rotamers, which rapidly rotated into the sp products
      that were enantiomeric with the substrates. These results are explained by the
      rotational restriction and partial steric hindrance by the tert-butyl group to
      the original face of the sp(3) antiaromatic 9-cation (4n pi electrons), and the
      rotational restriction and extensive blockage to the original face of the sp(2)
      nonaromatic 9-radical (4n + 1 pi electrons) and aromatic (4n + 2 pi electrons) 9
      anion. The barrier to rotation in some of the ortho-substituted 9-arylfluorenes
      is great enough to allow their sp and ap rotamers to be detected coexisting in
      solution, although their crystals were composed exclusively of one. Rotational
      restriction and steric hindrance at the 9-position have a large influence on the
      pK(a) values of these fluorenes and can offset the classic electronic effects of
      the substituents.

PMID- 14961670
TI  - Asymmetric induction of the iodolactonization reaction of alpha-sulfurated gamma
      unsaturated amides.
AB  - The 1,3-asymmetric iodolactonization reaction of enantiopure alpha-sulfurated
      gamma-unsaturated amides has been investigated. With sulfinyl and sulfonyl
      groups, a poorly stereoselective reaction was observed, whereas with a sulfanyl
      moiety, the diastereoselectivity can be high as 96:4. The role of the oxygen atom
      on the sulfur moiety is discussed.

PMID- 14961671
TI  - Incorporation of an allene unit into alpha-pinene: generation of the cyclic
      allene 2,7,7-trimethylbicyclo[4.1.1]octa-2,3-diene and its dimerization.
AB  - The reaction of etheral methyllithium with 3,3-dibromo-2,7,7-trimethyl
      tricyclo[4.1.1.0(2,4)]octane (2) was investigated. The generated carbene 12
      undergoes intramolecular C-H insertion to provide the tetracyclic hydrocarbon 3
      and the bicyclic allene 15, which undergoes [2+2] cyclodimerization. The
      structures of the formed allene dimers 16, 17, and 18 were elucidated by spectral
      means. The activation barriers for all possible C-H insertion products 3, 13, and
      14 and the allene 15 were investigated by using density functional theory
      computations at the B3LYP/6-31G(d) level. It was found that the activation
      barriers for the formation of 3 and 15 (6.2 and 6.3 kcal mol(-1)) are much lower
      than that for the insertion products 13 and 14 (17.5 and 12.6 kcal mol(-1)),
      respectively. This prediction was completely in agreement with our experimental
      results.

PMID- 14961672
TI  - An atom-economical approach to conformationally constrained tricyclic nitrogen
      heterocycles via sequential and tandem Ugi/intramolecular Diels-Alder reaction of
      pyrrole.
AB  - An efficient approach to rigid tricyclic nitrogen heterocycles via sequential and
      tandem Ugi/intramolecular Diels-Alder (IMDA) cycloaddition of pyrrole is
      described. The one-pot Ugi four-component condensation (4CC) reaction was used as
      the key transformation to prepare trienes with a carboxamide substituent on the
      tether. The use of acrylic acid (21) and N-propyl- and N-benzylmaleamic acids
      (24b and 24C) as the acid components provided trienes 22, 25b, and 25c,
      respectively, which upon heating at 120 degrees C for 12 h yielded the
      corresponding [4 + 2] cycloaddition products. In the case of maleic acid
      derivative 24a, heating the reaction mixture at 60 degrees C for 6 h promoted the
      cycloaddition reaction and provided the desired product 26a in 78% yield. In
      contrast, fumaric acid monoethyl ester (27a) and 3-acetyl- and 3-(4
      methylbenzoyl) acrylic acids (27b-c) directly yielded the corresponding Ugi/IMDA
      cycloaddition products 29a-c in high yields at room temperature without any trace
      of initially formed trienes 28a-c. The IMDA cycloaddition reactions proceed with
      excellent stereoselectivity with the formation of five stereogenic centers and
      three rings.

PMID- 14961673
TI  - Beta-lactam-forming photochemical reactions of N-trimethylsilylmethyl- and N
      tributylstannylmethyl-substituted alpha-ketoamides.
AB  - Two mechanisms have been proposed for the beta-lactam-forming photochemical
      reactions of alpha-ketoamides. One, suggested by Aoyama, involves excited-state H
      atom abstraction while the other, put forth by Whitten, follows a sequential SET
      proton-transfer route. The photochemical properties of N-trimethylsilylmethyl-
      and N-tributylstannylmethyl-substituted alpha-ketoamides were explored in order
      to gain information about the mechanism of this process and to develop a
      regioselective method for beta-lactam formation. The results of this effort show
      that (1) photoreactions of N-trimethylsilylmethyl-substituted alpha-ketoamides
      proceed by competitive H-atom abstraction and sequential SET-desilylation
      pathways and (2) a sequential SET-destannylation pathway is preferentially
      followed in photochemical reactions of the tributylstannylmethyl-substituted
      alpha-ketoamides.

PMID- 14961674
TI  - Pd(OAc)2-catalyzed oxidative coupling reaction of benzenes with olefins in the
      presence of molybdovanadophosphoric acid under atmospheric dioxygen and air.
AB  - The direct oxidative coupling reaction of benzenes with alkenes bearing an
      electron-withdrawing group was successfully achieved by the use of
      Pd(OAc)(2)/molybdovanadophosphoric acid (HPMoV) as the key catalyst under O(2) or
      air atmosphere. Thus, the reaction of benzene with ethyl acrylate under air (1
      atm) assisted by Pd(OAc)(2)/HPMoV afforded ethyl cinnamate as a major product in
      satisfactory yield (74%). This catalytic system could be extended to the coupling
      reactions between various substituted benzenes and alkenes through the direct
      aromatic C-H bond activation. In the reaction of benzene with ethyl acrylate
      under O(2) (1 atm), the best turn-over number (TON) of Pd(OAc)(2) reached was
      121. This reaction provides a green route to cinnamate derivatives, which are
      important precursors of a variety of pharmaceuticals.

PMID- 14961675
TI  - Remarkably facile solvolyses of triflates via carbocationic processes in dimethyl
      sulfoxide.
AB  - A number of triflates have been shown to undergo clean pseudo-first-order
      solvolysis reactions in DMSO-d(6) to give products derived from carbocationic
      intermediates. Thus, t-BuCH(OTf)CO-t-Bu (5) and t-BuCH(2)OTf (9) react readily in
      DMSO-d(6) at 25 degrees C to give a rearranged oxosulfonium salts, and subsequent
      alkene products where methyl migration to the incipient cationic center occurs. t
      BuCH(OTf)CO(2)CH(3) (14) gives analogous rearranged products, and 1
      methylcyclopropyl triflate (21) gives a ring-opened allylic oxosulfonium salt.
      These triflates react primarily via k(Delta) pathways. 6-Methylbicyclo[3.1.0]hex
      6-yl triflate (23), bicyclo[2.2.1hept-1-yl triflate (24), 1,6-methano[10]annulen
      11-yl triflate (25), (CH(3))(2)C(OTf)CO(2)CH(3) (26), and (CH(3))(2)CCN(OTf) (29)
      all react in DMSO-d(6) to give carbocation-derived products. PhCH(OTf)CF(3) (33)
      and substituted analogues also react readily in DMSO-d(6), and the Hammett rho(+)
      value is -3.7. This suggests a "borderline" mechanism where the transition state
      has substantial charge development. The primary feature of these solvolyses is
      the high reactivity of all of these triflates in DMSO-d(6). Thus, these triflates
      are all more reactive in DMSO-d(6) than in HOAc, and for most, rates are faster
      than in CF(3)CH(2)OH. Triflates 5, 21, 29, and 33 are 10(8)-10(9) times more
      reactive in DMSO-d(6) than the corresponding mesylates. It is suggested that the
      decreased need for electrophilic solvation of triflate anion, and the high cation
      solvating ability of DMSO, are the reasons for the high triflate reactivity in
      DMSO-d(6).

PMID- 14961676
TI  - Cycloadditions of 2-azaallyllithium species with conjugated polyenes.
AB  - 2-Azaallyllithium species [R(1)CH(-)N=C(X)R(2)Li(+), where R(1) and R(2) are
      alkyl and X = OMe] were generated by tin-lithium exchange of (2
      azaallyl)stannanes and underwent [pi4s+pi2s] and [pi6s+pi4s] cycloadditions with
      cyclic dienes and trienes, respectively, to generate novel bridged azabicyclic
      compounds in a highly diastereoselective endo fashion. The periselectivity using
      cycloheptatriene was modest, producing a 1:1 mixture of [pi6s+pi4s] and
      [pi4s+pi2s] adducts. The reactions of 2-azaallyllithium species with dienes
      proceeded by a [pi4s+pi2s] pathway. The cycloadducts derived from cyclic 2
      azaallyllithium species possess the 7-azabicyclo[2.2.1]heptane (tropane) or 8
      azabicyclo[3.2.1]octane ring system and have been elaborated into cocaine-like
      analogues.

PMID- 14961677
TI  - Planar chiral dianthranilide and dithiodianthranilide molecules: optical
      resolution, chiroptical spectra, and molecular self-assembly.
AB  - Planar chiral dianthranilide (1) was resolved to enantiomers with use of (-)
      (1S,4R)-camphanoyl chloride as a chiral derivatizing agent. The (+)-1 enantiomer
      was assigned the S absolute configuration from the X-ray crystal structure of its
      N,N'-dicamphanoyl derivative. Optical resolution of dithionodianthranilide (2)
      was accomplished by inclusion crystallization with (R,R)-1,2-diaminocyclohexane,
      and the X-ray structure of the corresponding adduct revealed the (-)
      2stereoisomer has the R configuration. A slow boat-to-boat ring inversion
      (DeltaG(++) = 24.1 +/- 0.1 kcal mol(-1)) causes racemization of (+)-1 in solution
      as manifested by a gradual decrease of the CD spectrum whereas, (-)-2 is
      configurationally stable at these conditions. The analysis of the CD spectra of
      the title compounds showed that the n-pi* Cotton effect signs are determined by
      the helicity of the skewed benzamide and thiobenzamide chromophores. The solid
      state structures of the racemic and homochiral forms of 1 and 2 show different
      self-assembly patterns: the racemate (+/-)-1 prefers the cyclic R(2)(2)(8)
      hydrogen bond motif, whereas the crystalline DMSO solvates of (+/-)-1 and (+)-1
      consist of 1D homochiral hydrogen-bonded assemblies generated by the C(6) motif.
      In the case of dithionolactams (+/-)-2 and (-)-2 two types of 1D networks were
      observed: in the racemate they are generated by the centrosymmetric R(2)(2)(8)
      and R(2)(2)(12) hydrogen bond motifs, whereas the molecules in the homochiral
      crystals are connected solely with use of the strongly nonplanar R(2)(2)(8)
      motif.

PMID- 14961678
TI  - Novel synthesis and properties of 1,6-methanocycloundeca[b]pyrimido[5,4-d]pyrrole
      12,14-dione derivatives: autorecycling oxidation of some amines and alcohols.
AB  - Novel 1,6-methanocycloundeca[b]pyrimido[5,4-d]pyrrole-12,14-dione derivatives
      6a,b and 7a-c were synthesized in moderate to good yields by the enamine
      alkylation and dehydrating condensation reactions of 11-chloro-3,8
      methano[11]annulenone (8) with 6-amino-3-substituted uracil derivatives and
      subsequent elimination of HCl. The (1)H NMR spectra clarified that compounds 6a,b
      and 7a-c are aromatic molecules having a diatropic pi-system, which is suggested
      by the chemical shifts of the bridge methylene protons and peripheral protons.
      The electrochemical reduction exhibited more positive reduction potentials as
      compared with those of the vinylogous compounds of cyclohepta[b]pyrimido[5,4
      d]pyrrole derivatives. In a search for the oxidizing function of 6a,b and 7a-c,
      compounds 6a and 7b were demonstrated to oxidize benzylamines, cyclohexylamine,
      and benzyl alcohol to give the corresponding carbonyl compounds in more than 100%
      yield under aerobic and photoirradiation conditions, while only benzylamine was
      oxidized under aerobic and thermal conditions at 100 degrees C. Thus, compounds
      6a and 7b oxidize amines and alcohols in an autorecyling process, and the
      efficiency is higher under photoirradiation as compared with the thermal process,
      suggesting the oxidation reaction probably proceeds via electron transfer from
      amine and alcohol to the excited and ground states of compounds 6a and 7b.

PMID- 14961679
TI  - An expedient and practical method for the synthesis of a diverse series of
      cyclopropane alpha-amino acids and amines.
AB  - A practical synthesis for the preparation of a diverse series of cyclopropane
      alpha-amino acids is described. Nitrocyclopropane carboxylates can be readily
      prepared through treatment of alpha-nitroesters and iodobenzene diacetate or
      alpha-nitro-alpha-diazoesters with a Rh(II) catalyst and an olefin. Reduction of
      the nitro group using zinc/HCl in i-PrOH affords substituted cyclopropane alpha
      amino esters in modest to high yields (54-99%). A "one-pot" procedure involving
      sequential cyclopropanation and reduction is described. The method can also be
      applied to the preparation of arylcyclopropyl amines (three examples).

PMID- 14961680
TI  - Catalytic, asymmetric synthesis and diastereoselective aldol reactions of
      dipropionate equivalents.
AB  - The dimer of methylketene can be conveniently prepared in one step and high
      enantiomeric excess from propionyl chloride, using a catalytic amount of a
      silylated cinchona alkaloid as a source of chirality. Opening of the dimer with a
      lithiated sulfonamide affords a beta-ketosulfonimide, which undergoes Sn(II)
      mediated aldol reactions to diastereoselectively afford the anti,syn-aldol
      adduct. Alternatively, reduction of the dimer to the beta-hydroxy ketone,
      followed by acylation, affords a beta-acyloxyl ketone that undergoes
      diastereoselective, dialkylboron chloride-mediated aldol reactions to produce the
      anti,anti-aldol adduct.

PMID- 14961681
TI  - Electrolytic partial fluorination of organic compounds.71. Highly
      diastereoselective anodic fluorination of sulfides having oxygen-containing
      heterocyclic groups.
AB  - Diastereoselective anodic fluorination of sulfides having various oxygen
      containing heterocyclic substituents such as 2-furanyl, 1,3-dioxolanyl, 2,2
      dimethyl-1,3-dioxolanyl, 2-spirocyclohexyl-1,3-dioxolanyl, 2-spiroadamantyl-1,3
      dixolanyl, and 1,3-dioxolanonyl groups at the beta-position was comparatively
      studied. Among the oxygen-containing heterocyclic substituents, the 2
      spirocyclohexyl-1,3-dioxolanyl group gave the best diastereoselectivity (80% de).
      The diastereoselectivity was also affected by supporting fluoride salts and
      solvents. Chemical fluorination using selectfluor resulted in much lower
      diastereoselectivity and extremely poor yield. The fluorinated products were
      readily converted into the corresponding fluorinated diol in good yields by
      acidic hydrolysis.

PMID- 14961682
TI  - Enantioselective total syntheses of (+)-arborescidine A, (-)-arborescidine B, and
      (-)-arborescidine C.
AB  - Described are the first enantioselective total syntheses of (+)-arborescidine A
      ((+)-1), (-)-arborescidine B ((-)-2), and (-)-arborescidine C ((-)-3), via routes
      that proceeded in five steps and 50% overall yield, eight steps and 61% overall
      yield, and nine steps and 51% overall yield, respectively, from 6-bromotryptamine
      (7). The syntheses feature the use of the Noyori catalytic asymmetric hydrogen
      transfer reaction to introduce chirality in dihydro-beta-carbolines 6 and 8. On
      the basis of an ample precedent from Noyori's work, the reduction produces
      dihydro-beta-carbolines, and ultimately the natural products, possessing the R
      absolute configuration. The synthetic arborescidines displayed optical rotations
      that were opposite in sign those of the natural products, thereby supporting the
      S configuration for natural arborescidines A (1) and B (2) and the (3S,17S)
      configuration for natural arborescidine C (3). Our results are in agreement with
      the initial stereochemical assignment by Pais and co-workers, and are counter to
      their recently revised assignment.

PMID- 14961683
TI  - Investigation into the allylation reactions of aldehydes promoted by the
      CeCl3.7H2O-NaI system as a Lewis acid.
AB  - The Lewis acid promoted allylation of aldehydes has become an important carbon
      carbon bond forming reaction in organic chemistry. In this context, we have
      developed an alternative over existing catalytic processes, wherein aldehydes are
      subject in acetonitrile to reaction of allylation with allyltributylstannane in
      the presence of 1.0 equiv of cerium(III) chloride heptahydrate (CeCl(3).7H(2)O),
      an inexpensive and mild Lewis acid. The allylation has been accelerated by using
      an inorganic iodide as a cocatalyst, and various iodide salts were examined. The
      procedure must use allylstannane reagent instead of allylsilane reagent,
      desirable for environmental reasons, but high chemoselectivity was observed, and
      this is opposite the results obtained with other classical Lewis acids such as
      TiCl(4) and Et(2)O.BF(3).

PMID- 14961684
TI  - Demonstrating the synergy of synthetic, mechanistic, and computational studies in
      a regioselective aniline synthesis.
AB  - Tri- and tetrasubstituted anilines are formed in good to excellent yields by the
      addition of ketones to vinamidinium salts (up to 98%). The reaction proceeds via
      the formation of dienone intermediates, which react to form an enamine with the
      liberated amine. In the case of a nitro, or dimethylaminomethylene substituent,
      the enamines undergo a facile electrocyclic ring closure to form a
      cyclohexadiene, which goes on to form anilines with a high degree of selectivity
      (up to 50:1) with a minor competing pathway proceeding via the enol providing
      phenols. Competition experiments using isotopic substitution reveal that the rate
      determining step en route to dienone is enol/enolate addition to the vinamidinium
      salt, which is characterized by an inverse secondary isotope effect (k(H/D) 0.7
      0.9). Computational studies have been used to provide a framework for
      understanding the reaction pathway. The original proposal for a [1,5]-H shift was
      ruled out on the basis of the calculations, which did not locate a thermally
      accessible transition state. The minimum energy conformation of the enamine is
      such that a facile electrocyclic ring closure is ensured, which is corroborated
      by the experimental studies. A framework for understanding the reaction pathway
      is presented.

PMID- 14961685
TI  - Controllable enantioselective Friedel-Crafts reaction between indoles and
      alkylidene malonates catalyzed by pseudo-C3-symmetric trisoxazoline copperII
      complexes.
AB  - Pseudo-C(3)-symmetric trisoxazoline copper(II) complexes prove to be excellent
      catalysts in the Friedel-Crafts alkylation of indoles with alkylidene malonates.
      The absolute stereochemistry of this reaction is shown to be dependent on the
      solvent. Reactions in isobutyl alcohol afford the Friedel-Crafts alkylation
      adducts in excellent yields and with up to +98% ee. In 1,1,2,2-tetrachloroethane
      (TTCE), however, the opposite enantiomers of the products are obtained in good
      yields with up to -89% ee. Water tolerance of chiral catalyst trisoxazoline
      2a/Cu(OTf)(2) is examined, and it is found that the addition of up to 200 equiv
      of water relative to catalyst in isobutyl alcohol has almost no effect on
      enantioselectivity but slows down the reaction. The reaction scope is studied as
      well. The roles of alcohol as the solvent to accelerate the reaction are
      discussed. The stereochemical models of asymmetric induction for reactions both
      in isobutyl alcohol and in TTCE are also developed.

PMID- 14961686
TI  - Influence of conformation on the EPR spectrum of 5,5-dimethyl-1-hydroperoxy-1
      pyrrolidinyloxyl: a spin trapped adduct of superoxide.
AB  - Spin trapping, a technique used to characterize short-lived free radicals,
      consists of using a nitrone or nitroso compound to "trap" an unstable free
      radical as a long-lived aminoxyl that can be characterized by EPR spectroscopy.
      The resultant aminoxyl exhibits hyperfine splitting constants that are dependent
      on the spin trap and the free radical. Such is the case with 2,2-dimethyl-5
      hydroxy-1-pyrrolidinyloxyl (DMPO-OH) and 2,2-dimethyl-5-hydroperoxy-1
      pyrrodinyloxyl (DMPO-OOH) whose hyperfine splitting constants, A(N) = A(H) = 14.9
      G and A(N) = 14.3 G, A(H)(beta) = 11.7 G, and A(H)(gamma) = 1.25 G, respectively,
      have been used to demonstrate the generation of HO(*) and O(2)(*)(-). However, to
      date, the source of the apparent A(H)(gamma) hyperfine splitting in DMPO-OOH is
      not known. We consider three possible explanations to account for the unique EPR
      spectrum of DMPO-OOH. The first is that the gamma-splitting arises from one of
      the hydrogen atoms at either carbon 3 or carbon 4 of DMPO-OOH. The second is that
      the gamma-splitting originates from the hydrogen atom of DMPO-OOH. The third is
      that the conformational properties of DMPO-R change upon going from DMPO-OH to
      DMPO-OOH. Experimental and theoretical chemical approaches as well as EPR
      spectral modeling were used to investigate which of these hypotheses may explain
      the asymmetric EPR spectrum of DMPO-OOH. From these studies it is shown that the
      12-line EPR spectrum of DMPO-OOH results not from any proximal hydrogen, but from
      additional conformers of DMPO-OOH. Thus, the 1.25 G hyperfine splitting, which
      has been assigned as a gamma-splitting, is actually from two individual EPR
      spectra associated with different conformers of DMPO-OOH.

PMID- 14961687
TI  - [3 + 2] Cycloreversion of bicyclo[m.3.0]alkan-3-on-2-yl-1-oxonium ylides to
      alkenyloxyketenes. Stereospecific aspect.
AB  - Rhodium(II)-catalyzed intramolecular reaction of diazoketones 1 bearing a cyclic
      ethereal moiety transiently formed bicyclo[m.3.0]octan-3-one-1-oxonium-2-ylides
      (2), which underwent sigmatropic and stereospecific [3 + 2] cycloreversion
      reaction to form alkenyloxyketenes 3. The ketenes were efficiently trapped by
      methanol to form the corresponding esters 4. Mechanistic studies revealed that
      the size of ethereal ring can be variable at least from THF to the THP, oxepane,
      and oxocane moiety, i.e., m = 3-6. On the other hand, the size of the ylide ring
      containing the carbonyl unit is limited to a five-membered ring. The
      cycloreversion was found to be stereospecific as was proven by the reactions of
      diastereoisomeric pairs bearing a methyl group at the bond-cleaving position.
      From threo isomers 7, (E)-alkenyloxyacetates 15 were exclusively formed (77-84%),
      whereas from erythro isomers 8, (Z)-isomers 16 were formed (80-88%). Mechanism of
      the cleavage from diazoacetonyl-substituted cyclic ethers to alkenyloxyketenes
      via bicyclic oxonium ylides was analyzed on the basis of calculations employing
      the hybrid density functional B3LYP and the highly correlated quadratic
      configuration interaction QCISD method to reveal that the concerted [3 + 2]
      cycloreversion is the key step of this reaction.

PMID- 14961688
TI  - Design and synthesis of new macrocyclic cyclophanes using 1,3-dioxane units as
      bridges: a molecular "rocking chair".
AB  - The design, synthesis and structural analysis of architecturally new cyclophanes
      (monomers, dimers, and trimers) are reported. Variable temperature NMR
      experiments reveal a regular, tandem dynamic in the cyclophane 2a that enables
      its description as a "molecular rocking chair". The NMR and X-ray structure
      investigations show important intra- and intermolecular aromatic pi-stacking
      interactions.

PMID- 14961689
TI  - Synthesis of fused tetrazole derivatives via a tandem cycloaddition and N
      allylation reaction and parallel synthesis of fused tetrazole amines.
AB  - A method for the synthesis of novel fused tricyclic tetrazoles from allylic
      bromides generated by the recently discovered DiazAll reaction has been
      developed. This new tandem reaction comprises a cycloaddition between a nitrile
      and (TMS)N(3) followed by an intramolecular N-allylation. The variation of
      functionalities in the benzene moiety was well-tolerated, and only a moderate
      difference in yield and degree of purity was noticed. An exo-methylene group in
      these new compounds permitted further derivatization. Structural resemblance with
      substances which possess important pharmacological properties motivated the
      synthesis of a series of ketones and a small library of amines.

PMID- 14961690
TI  - Preparation of bicyclo[3.2.0]heptane-2-endo,7-endo-diols: 1,3-diols with a chiral
      rigid backbone.
AB  - The easily available bicyclo[3.2.0]hept-3-en-6-ones (1a-f) have been converted
      into the corresponding bicyclo[3.2.0]heptane-2-endo,7-endo-diols (4a-f) in an
      efficient and stereoselective fashion. This preparation opens a route to a family
      of 1,3-diols with a chiral rigid backbone, potentially suitable as nonracemic
      precursors for bidentate ligands in asymmetric synthesis.

PMID- 14961691
TI  - Cyanide-catalyzed cyclizations via aldimine coupling.
AB  - Aldimine coupling (AIC) is the nitrogen analogue of the benzoin condensation and
      has been applied to dialdimines, providing the first examples of cyclizations
      effected by cyanide-catalyzed AIC. Sodium cyanide promoted the facile,
      intramolecular cyclization of several dialdimines in N,N-dimethylformamide,
      methanol, or methylene chloride/water (phase-transfer conditions) yielding a
      variety of six-membered heterocycles. Under aerobic conditions, an oxidative
      cyclization occurs to provide the diimine heterocycle. Oligomerization was
      observed with rigid dialdimines for which cyclization was precluded.

PMID- 14961692
TI  - Dialkylaminoacetonitrile derivatives as amide synthons. A one-pot preparation of
      heteroaryl amides via a strategy of sequential SNAr substitution and oxidation.
AB  - Dialkylamino acetonitrile derivatives were utilized as alternative to cyanohydrin
      synthons for preparation of the corresponding heteroaryl dialkyl amides via a
      strategy of sequential base-mediated coupling and oxidation. The most
      advantageous oxidant, NiO(2)-H(2)O, can readily oxidize 2-substituted
      aminoacetonitriles to the corresponding amides under both basic and neutral
      conditions by forming cyanohydrins in situ.

PMID- 14961694
TI  - N-Amination of pyrrole and indole heterocycles with monochloramine (NH2Cl).
AB  - A survey of several electrophilic ammonia reagents for the N-amination of indole-
      and pyrrole-containing heterocycles revealed that monochloramine (NH(2)Cl) is an
      excellent reagent for this transformation. Pyrroles and indoles containing a
      variety of substitution were aminated on nitrogen with isolated yields ranging
      from 45% to 97%.

PMID- 14961693
TI  - Acetonitrile derivatives as carbonyl synthons. One-pot preparation of
      diheteroaryl ketones via a strategy of sequential SNAr substitution and
      oxidation.
AB  - The anion of 2-aryl acetonitrile derivatives reacted with a variety of heteroaryl
      chlorides or bromides in an S(N)Ar manifold to afford intermediate anions which
      were susceptible to oxidation. The addition of sodium peroxide and aqueous
      NH(4)OAc solution effected oxidation to afford aryl heteroaryl ketones in good
      yields. Aryl acetonitrile derivatives are thus umpolung-type synthons of the
      corresponding aryl carbonyl functionality.

PMID- 14961695
TI  - A convenient new synthesis of benzo[a]pyrene.
AB  - A convenient new synthesis of the ubiquitous environmental carcinogen
      benzo[a]pyrene (BaP) is described. In the key step, the method entails Suzuki
      coupling of naphthalene 2-boronic acid with 2-bromobenzene-1,3-dialdehyde and
      requires only three steps. It is considerably shorter and simpler than the older
      methods and provides BaP in higher overall yield.

PMID- 14961696
TI  - Concise synthesis of dihydrochalcones via palladium-catalyzed coupling of aryl
      halides and 1-aryl-2-propen-1-ols.
AB  - An expedient route to substituted dihydrochalcones is reported. The key step is a
      palladium-assisted arylation of 1-aryl-2-propen-1-ols. This two-step/one
      purification process allows the synthesis of a wide range of compounds with
      original substitution patterns, including polyphenolic derivatives.

PMID- 14961697
TI  - Extension of the tandem conjugate addition-Dieckmann condensation: the formal
      synthesis of tetracenomycin A2.
AB  - Tandem cuprate addition-Dieckmann condensation is featured in the construction of
      the polyketide metabolite tetracenomycin A(2). Thus, cyclization substrate 11 was
      treated with Gilman cuprate Me(2)CuLi to afford anthracene 12. The phenolic
      acetate protecting group of 12ensured its chemoselective oxidation to reveal
      terminal quinone 13, which intercepts the previously reported synthesis of
      tetracenomycin A(2).

PMID- 14961698
TI  - Metallo-aldehyde enolates via enal hydrogenation: catalytic cross aldolization
      with glyoxal partners as applied to the synthesis of 3,5-disubstituted
      pyridazines.
AB  - Aldehyde enolates generated through rhodium-catalyzed enal hydrogenation are
      subject to electrophilic trapping by exogenous glyoxal partners to afford beta
      hydroxy-gamma-keto-aldehyde products, which upon exposure to hydrazine afford 3,5
      disubstituted pyridazines in moderate yield in a two-step, one-pot sequence.

PMID- 14961699
TI  - Salt effects on the apparent stability of the cucurbit[7]uril-methyl viologen
      inclusion complex.
AB  - The effects of the medium ionic composition on the apparent equilibrium
      association constant (K) for the formation of a 1:1 inclusion complex between the
      guest methyl viologen (MV(2+)) and the host cucurbit[7]uril (CB7) were studied in
      aqueous solutions. The K values were found to decrease with increasing ionic
      strength, with more pronounced effects for solutions containing divalent Ca(2+)
      ions than for solutions containing monovalent Na(+) ions. The competing ion
      dipole interactions between Ca(2+) or Na(+) and MV(2+) ions appear to be
      responsible for the remarkable modulation of the K values observed in this work.

PMID- 14961700
TI  - Synthesis of cavity extended cyclotriveratrylenes.
AB  - Aromatic nucleophilic substitution reaction of cyclotriguaiacylene 1 with
      fluorobenzene derivatives bearing electron-withdrawing groups X (CHO, COCH(3),
      CN, NO(2)) in the para position gives a series of cyclotriveratrylene derivatives
      (3a-d), where the X substituents can be transformed to hydrogen-bond donor groups
      to afford new CTV-based heteroditopic receptors. The substituents of compounds 3a
      d favor the facile demethylation reaction of the CTV derivatives. Attempts to
      perform alkylation reactions on derivatives (8c,d) evidenced the formation of a
      stereoisomeric mixture of symmetrical and unsymmetrical compounds.

PMID- 14961701
TI  - Desymmetrization of meso-hydrobenzoin using chiral, nucleophilic phosphine
      catalysts.
AB  - The desymmetrization of meso-hydrobenzoin is described using chiral phosphine
      catalysts 8b-d and 9-11. The best enantioselectivity at room temperature was
      obtained with the newly synthesized phospholane 8c and benzoic anhydride, but the
      reaction is very slow. Much faster reactions, but somewhat lower
      enantioselectivities were observed using the bicyclic phosphine catalyst 9. To
      obtain product 5a with >90% ee required conditions where the ee is upgraded due
      to the formation of the dibenzoate 6a. Among the new phospholane catalysts, 8b
      has the best selectivity in the kinetic resolution of benzylic alcohols, but not
      at the level observed previously with catalyst 11.

PMID- 14961702
TI  - Catalysis in the self-assembly of [2]rotaxanes and [2]pseudorotaxanes. Effect of
      the length of polyethereal side arms and terminal stoppers.
AB  - The template effects exerted by compounds 3, 5, 6, and 8 in the ring closure
      reaction of the trication 1(3+) to yield the [2]pseudorotaxanes 15(4+) and 17(4+)
      and the [2]rotaxanes 18(4+) and 20(4+) have been quantitatively evaluated in
      acetonitrile at 62 degrees C by UV/vis spectrophotometry. The rate of ring
      closure of the trication 1(3+) largely increases in the presence of the templates
      up to a maximum of ca. 200 times in the case of 5 at a concentration of ca. 0.08
      M. The results indicate that, in the self-assembly of a rotaxane, the template
      effect of the guest is lowered by the presence of two large stoppers
      (triisopropylsilyl) at the end of the linear chains; this effect is more
      important the shorter the chain and can be mainly ascribed to steric effects.
      Previously hypothesized entropic effects appear to be of lesser importance.

PMID- 14961703
TI  - The first 1-alkyl-3-perfluoroalkyl-4,5- dimethyl-1,2,4-triazolium salts.
AB  - Syntheses of quaternary 1-alkyl-3-perfluoroalkyl-4,5-dimethyl-1,2,4-triazolium
      iodides have led to a variety of new quaternary salts via metathesis reactions.
      1,4,5-Trimethyl-3-trifluoro-methyl-1,2,4-triazolium iodide (6) with
      LiN(SO(2)CF(3))(2), KSO(3)CF(3), AgClO(4), AgBF(4); 1-(3-fluoropropyl)-3
      trifluoromethyl-4,5-dimethyl-1,2,4-triazolium iodide (7) with LiN(SO(2)CF(3))(2);
      and 1,4,5-trimethyl-3-perfluorooctyl-1,2,4-triazolium iodide (8) with
      LiN(SO(2)CF(3))(2), AgClO(4), AgBF(4) gave excellent yields of new thermally
      stable and relatively low melting quaternary salts. The structure of 1,4,5
      trimethyl-3-perfluorooctyl-1,2,4-triazolium tetrafluoroborate (11c) was confirmed
      by single-crystal X-ray analysis. Although the molecular weight of 11c (cation)
      is 3-fold greater than that of the 3-trifluoromethyl derivative 9d, its melting
      point is 32 degrees C lower.

PMID- 14961704
TI  - Synthesis of aryl- and heteroaryl-substituted 3-benzyloxyisothiazoles via Suzuki
      and Negishi cross-coupling reactions.
AB  - Introduction of aryl and heteroaryl substituents into the 5-position of 3
      benzyloxyisothiazole (1) using palladium-catalyzed Suzuki and Negishi cross
      coupling reactions was investigated. Attempts to generate synthetically viable
      nucleophilic species from 1 for Suzuki- or Negishi-type cross-couplings were
      unsuccessful. However, using 3-benzyloxy-5-iodoisothiazole 2 as an intermediate,
      a range of aromatic and heteroaromatic substituents were successfully introduced
      under Suzuki or Negishi cross-coupling conditions in good to excellent yields.

PMID- 14961705
TI  - Synthesis and dienophilic behavior of (S)-2-cyano-3-(p-tolylsulfinyl)-1,4-
      benzoquinone.
AB  - Hydrocyanation of 2-(p-tolylsulfinyl)-1,4-benzoquinone (2) followed by oxidation
      with PhI(OAc)(2) gives 2-cyano-3-(p-tolylsulfinyl)-1,4-benzoquinone (1). The
      generation of 1 in the presence of cyclic and acyclic dienes affords the Diels
      Alder adducts with a complete chemo- (only reaction with the sulfinyl-substituted
      double bond takes place), regio- (controlled by the cyano group), and endo
      selectivity (with respect to the quinone moiety), whereas the pi-facial
      selectivity is dependent on the structure of the diene.

PMID- 14961706
TI  - Two-step asymmetric synthesis of disubstituted N-tosyl aziridines having 98-100%
      ee: use of a phosphazene base.
AB  - Unknown diaryl (1-3) and alkyl-phenyl (4, 5) N-tosyl aziridines have been
      successfully synthesized from pure (R,R,R,S(S))-(-)-sulfonium salt derived from
      Eliel's oxathiane, tosylimines 11a-f, and using a phosphazene base (EtP(2)) to
      generate the ylide. Both cis and trans aziridines have exceptionally high
      enantiomeric purities (98.7-99.9%). The (2R,3R)-configuration of trans-3 and the
      (2R,3S)-configuration of cis-4 have been determined by X-ray analysis using the
      Bijvoet method. The R-configuration found at C2 is consistent with the model and
      all previous results, therefore all trans-aziridines and cis-aziridines have been
      assigned the (2R,3R)- and the (2R,3S)-configurations, respectively. This two-step
      asymmetric synthesis can be easily used on gram quantities and involves no
      unstable/hazardous reagent. The chiral auxiliary is used in a stoichiometric
      amount but is recovered in high yield and reused.

PMID- 14961707
TI  - The three-component reaction of dicarbomethoxycarbene, aldehydes, and beta
      nitrostyrenes: a stereoselective synthesis of substituted tetrahydrofurans.
AB  - The Rh(II)-catalyzed reaction of dimethyl diazomalonate with aryl aldehydes and
      beta-nitrostyrenes results in the formation of highly substituted
      tetrahydrofurans. The reaction may be considered to involve the Huisgen dipolar
      cycloaddition of the carbonyl ylide, generated from the dicarbomethoxycarbene and
      the aldehyde, to the beta-nitrostyrene. The diastereoselectivity of the reaction
      may be attributed to the concerted nature of the carbonyl ylide cycloaddition.

PMID- 14961708
TI  - Palladium-indium iodide-mediated allylation and propargylation of glyoxylic oxime
      ether and hydrazone: the role of water in directing the diastereoselective
      allylation.
AB  - Allylation and propargylation of glyoxylic oxime ether in the presence of a
      catalytic amount of palladium(0) complex and indium(I) iodide were studied.
      Excellent diastereoselectivities in allylation were achieved in the presence of
      water, although low diastereoselectivities were observed in the absence of water.
      Propargylation of glyoxylic oxime ether proceeded with good
      diastereoselectivities in the presence of LiBr or LiCl.

PMID- 14961709
TI  - Converting exo-selective Diels-Alder reaction to endo-selective in
      chloroloaluminate ionic liquids.
AB  - The endo:exo ratio of 0.35:1 for the reaction of cyclopentadiene with methyl
      methacrylate observed in organic solvents can be converted to 3:1 in
      chloroaluminate ionic liquids with their effective reuse in Diels-Alder
      reactions.

PMID- 14961710
TI  - Ring-closing olefin metathesis and radical cyclization as competing pathways.
AB  - First and second generation Grubbs' catalyst mediate under otherwise identical
      conditions two different cyclization modes with high selectivity: a ring-closing
      metathesis and an atom-transfer radical addition (ATRA) pathway.

PMID- 14961711
TI  - Efficient synthesis of azide-bearing cofactor mimics.
AB  - 8-Azido-5'-aziridino-5'-deoxyadenosine (6), a novel cofactor mimic, was
      synthesized in nine steps from commercially available 2',3'
      isopropylideneadenosine in approximately 4% overall yield. Crucial to this
      success was a very unorthodox phthalimide cleavage procedure, C8 azidation prior
      to aziridination and late stage alkylation of the 5' amino group with iodoethanol
      necessitated by the high degree of lability endowed by the aryl azide moiety.
      Aziridine 6 is envisioned as a useful biochemical tool by which to probe DNA and
      protein methylation patterns.

PMID- 14961712
TI  - An efficient synthesis of 4-Halo-5-hydroxyfuran-2(5H)-ones via the sequential
      halolactonization and gamma-hydroxylation of 4-aryl-2,3-alkadienoic acids.
AB  - 4-Halo-5-hydroxyfuran-2(5H)-ones were synthesized via the efficient sequential
      halolactonization-hydroxylation reaction of 4-aryl-2,3-allenoic acids with I(2)
      or CuX(2) (X = Br or Cl) in moderate to good yields. The structures of the
      products were established by the X-ray single-crystal diffraction study of 3
      methyl-4-iodo-5-phenyl-5-hydroxyl-2(5H)-furanone (2a). A rationale for this
      reaction was discussed based on some brief mechanistic study.

PMID- 14961713
TI  - Conversion of phenyl-substituted cyclopentadienes to pyrylium cations.
AB  - Phenyl-substituted cyclopentadienes are proved to form phenylated pyrylium
      cations in the presence of silver(I) perchlorate by insertion of an oxygen atom
      into the cyclopentadiene-ring. Three phenylated pyrylium compounds,
      [(Ph(5)C(5)O(+))(ClO(4)(-))](2)(CH(2)Cl(2)) (1),
      Ag(ClO(4))(H(2)O)(Ph(4)HC(5)O(+)) (ClO(4)(-)) (2), and
      (Ph(3)H(2)C(5)O(+))(ClO(4)(-)) (3) have been synthesized and characterized. A
      possible reaction pathway and formation mechanism of the pyrylium cation are
      proposed and discussed.

PMID- 14961714
TI  - Identification of 4-hydroxy-2-nonenal-modified peptides within unfractionated
      digests using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry.
AB  - The lipid peroxidation product 4-hydroxy-2-nonenal (HNE) is generated as a
      consequence of oxidative stress and can readily react with nucleophilic sites of
      proteins (e.g., histidine residues), mainly via a Michael addition. The formation
      of such lipid-protein conjugates can alter protein properties and biological
      functions, thus leading to highly deleterious effects. The present work describes
      a rapid (very limited sample preparation) and sensitive (low-femtomole range)
      procedure to identify HNE-modified peptides (Michael adducts) within
      unfractionated tryptic digests. The protocol involves the formation of
      dinitrophenylhydrazones of the Michael adducts, when using 2,4
      dinitrophenylhydrazine as reactive matrix, followed by analysis using matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI
      TOFMS). The hydrazone derivatives present high desorption/ionization yield and
      can thus be preferentially detected compared to unmodified peptides. The MALDI
      mass spectrum obtained is therefore drastically different from the one obtained
      with the classical 4-hydroxy-alpha-cyanocinnamic acid matrix. Moreover, the
      presence of HNE, or more generally speaking carbonylated peptides, could be
      highlighted by 180 mass units differences (corresponding to the
      dinitrophenylhydrazone moiety) between these two MALDI mass spectra. Further
      information (e.g., localization/identification of the modified residues, peptide
      sequences) could be obtained by performing MALDI postsource decay (or
      electrospray) MS/MS experiments on the ions of interest.

PMID- 14961715
TI  - DNA mutation detection in a polymer microfluidic network using temperature
      gradient gel electrophoresis.
AB  - A miniaturized system for DNA mutation analysis, utilizing temperature gradient
      gel electrophoresis (TGGE) in a polycarbonate (PC) microfluidic device, is
      reported. TGGE reveals the presence of sequence heterogeneity in a given
      heteroduplex sample by introducing a thermal denaturing gradient that results in
      differences between the average electrophoretic mobilities of DNA sequence
      variants. Bulk heater assemblies are designed and employed to externally generate
      temperature gradients in spatial and temporal formats along the separation
      channels. TGGE analyses of model mutant DNA fragments, each containing a single
      base substitution, are achieved using both single- and 10-channel parallel
      measurements in a microfluidic platform. Additionally, a comprehensive polymer
      microfluidic device containing an integrated microheater and sensor array is
      developed and demonstrated for performing spatial TGGE for DNA mutation analysis.
      The device consists of two PC modular substrates mechanically bonded together.
      One substrate is embossed with microchannels, and the other contains a tapered
      microheater, lithographically patterned along with an array of temperature
      sensors. Compared with the external heating approaches, the integrated platform
      provides significant reduction in power requirement and thermal response time
      while establishing more accurate and highly effective control of the temperature
      gradient for achieving improved separation resolution.

PMID- 14961716
TI  - Binding of fluorescent dye to genomic RNA inside intact human rhinovirus after
      viral capsid penetration investigated by capillary electrophoresis.
AB  - RiboGreen is used for concentration measurements of RNA. Upon binding to the RNA,
      an approximately 1000-fold increase in sensitivity in comparison with the UV
      absorbance of the free polynucleotide is observed. In the present work, we
      demonstrate that this dye can penetrate in a time- and temperature-dependent
      manner the intact viral capsids of human rhinovirus serotypes 2 and 14, where it
      forms a fluorescent complex with the viral RNA. Capillary electrophoresis with
      laser-induced fluorescence detection of virus incubated with RiboGreen shows that
      the electrophoretic mobility of the viruses remained unchanged upon dye-binding.
      As shown for human rhinovirus serotype 2, its native conformation was conserved,
      since it still bound a recombinant soluble receptor fragment derived from the
      very low density lipoprotein receptor. The labeled RNA was released by heat
      induced uncoating of the virus, and the RNA-dye complex could be directly
      detected if degradation was prevented with an RNase inhibitor. This in vitro
      labeling of viral RNA encased within a protein shell demonstrates the virion's
      dynamic nature that temporarily allows access of a low-molecular-mass compound to
      the otherwise protected RNA. It might be of great value for experiments requiring
      fluorescent viral particles with an unmodified surface, such as investigations of
      endocytosis and viral uncoating on the single molecule level.

PMID- 14961717
TI  - A universal nucleic acid sequence biosensor with nanomolar detection limits.
AB  - A quantitative universal biosensor was developed on the basis of olignucleotide
      sandwich hybridization for the rapid (30 min total assay time) and highly
      sensitive (1 nM) detection of specific nucleic acid sequences. The biosensor
      consists of a universal membrane and a universal dye-entrapping liposomal
      nanovesicle. Two oligonucleotides, a reporter and a capture probe that can
      hybridize specifically with the target nucleic acid sequence, can be coupled to
      the universal biosensor components within a 10-min incubation period, thus
      converting it into a specific assay. The liposomal nanovesicles bear a generic
      oligonucleotide sequence on their outer surface. The reporter probes consist of
      two parts: the 3' end is complementary to the generic liposomal oligonucleotide,
      and the 5' end is complementary to the target sequence. Streptavidin is
      immobilized in the detection zone of the universal membranes. The capture probes
      are biotinylated at the 5' end and are complementary to another segment in the
      target sequence. Thus, by incubating the liposomal nanovesicles with the reporter
      probes, the target sequence, and the capture probes in a hybridization buffer for
      20 min, a sandwich complex is formed. The mixture is applied to the membrane,
      migrates along the strip, and is captured in the detection zone via streptavidin
      biotin binding. The biosensor assay was optimized with respect to hybridization
      conditions, concentrations of all components, and length of the generic probe. It
      was tested using synthetic DNA sequences and authentic RNA sequences isolated and
      amplified using nucleic acid sequence-based amplification (NASBA) from
      Escherichia coli, Bacillus anthracis, and Cryptosporidium parvum. Dose-response
      curves were carried out using a portable reflectometer for the instantaneous
      quantification of liposomal nanovesicles in the detection zone. Limits of
      detection of 1 fmol per assay (1 nM) and dynamic ranges between 1 fmol and at
      least 750 fmol (1-750 nM) were obtained. The universal biosensors were compared
      to specific RNA biosensors developed earlier and were found to match or exceed
      their performance characteristics. In addition, no changes to hybridization
      conditions were required when switching to the detection of a new target sequence
      or when using actual nucleic acid sequence-based amplified RNA sequences.
      Therefore, the universal biosensor described is an excellent tool for use in
      laboratories or at test sites for rapidly investigating and quantifying any
      nucleic acid sequence of interest.

PMID- 14961718
TI  - Nanoliter-sized liquid dispenser array for multiple biochemical analysis in
      microfluidic devices.
AB  - We have developed a microdispenser array made of PDMS, in which a number of
      nanoliter-sized droplets can be accurately dispensed and mixed with the aid of
      specific channels under pneumatic pressure. In this system, hydrophobic and
      narrow channels act as a kind of valve and help structural liquid manipulation.
      Also, by arranging multiple dispensers in parallel, a single injection of liquid
      becomes sufficient for the preparation of multiple nanoliter-sized aliquots for
      different reactions. We designed two kinds of microdevices for multiple liquid
      dispensing and mixing and evaluated their performance and reproducibility,
      proving them sufficient for quantitative reactions. As a practical application,
      biochemical analysis of glucose was performed using enzymatic reactions. This
      liquid dispensing technology can be widely applied in the field of microscale
      analysis due to its low consumption, small dead volume of reagents and samples,
      and ease of operation.

PMID- 14961719
TI  - Electrochemical sensing of DNA hybridization based on duplex-specific charge
      compensation.
AB  - A nonlabeling voltammetric detection method for DNA hybridization has been
      developed, in which [Fe(CN)(6)](3-) in solution can readily approach an electrode
      surface covered with a charge-compensated DNA duplex layer and thus provides a
      strong redox-sensing current. Charge compensation for negative charges on the DNA
      backbone has been specifically accomplished on DNA duplexes by discouraging
      nonspecific binding of positively charged intercalating molecules with single
      strands. A pretreatment of DNA-modified electrodes with sodium dodecyl sulfate
      before the intercalator binding process is essential in preventing the
      nonspecific binding. Since ferricyanide, the only electrochemically active
      species, is present in the voltammetric solution, the detection signal can be
      amplified by increasing its concentration. Combination of the duplex-specific
      charge compensation with the signal amplification has achieved a remarkable
      signal difference: in 30 mM [Fe(CN)(6)](3-), the area ratio between cyclic
      voltammograms of the hybridized and unhybridized electrodes is approximately 200
      when 3,6-diaminoacridine is used as the intercalator. High sensitivity of the
      method has been demonstrated by detecting 10 fM (100 zmol in amount) of a target
      probe DNA.

PMID- 14961720
TI  - Quantitative methods for spatially resolved adsorption/desorption measurements in
      real time by surface plasmon resonance microscopy.
AB  - A simple method for converting local reflectivity changes measured in surface
      plasmon resonance (SPR) microscopy to effective adlayer thicknesses and absolute
      surface coverages of adsorbed species is presented. For a range of high-contrast
      angles near the SPR resonance where the local metal surface's reflectivity
      changes linearly with angle, the change in reflectivity at fixed angle is
      proportional to the change in effective refractive index (eta(eff)) near the
      surface. This change in eta(eff) can be converted to absolute adsorbate coverage
      using methods developed for quantitative SPR spectroscopy. A measurement of the
      change in reflectivity due to changes in refractive index of bulk solutions,
      i.e., percent reflectivity change per refractive index unit (RIU), is the only
      calibration required. Application of this method is demonstrated for protein
      adsorption onto protein/DNA arrays on gold from aqueous solution using an SPR
      microscope operating at 633 nm. A detection limit of 0.072% change in absolute
      reflectivity is found for simultaneous measurements of all 200 microm x 200
      microm areas within the 24-mm(2) light beam with 1-s time averaging. This
      corresponds to a change in effective refractive index of 1.8 x 10(-5) and a
      detection limit for protein adsorption of 1.2 ng/cm(2) (approximately 0.5 pg in a
      200-microm spot). The linear dynamic range is Deltaeta(eff) = approximately 0.011
      RIU or approximately 720 ng/cm(2) of adsorbed protein. Using a nearby spot as a
      reference channel, one can correct for instrumental drift and changes in
      refractive index of the solutions in the flow cell.

PMID- 14961721
TI  - Microspotting streptavidin and double-stranded DNA arrays on gold for high
      throughput studies of protein-DNA interactions by surface plasmon resonance
      microscopy.
AB  - We present two strategies for microspotting 10 x 12 arrays of double-stranded
      DNAs (dsDNAs) onto a gold-coated glass slide for high-throughput studies of
      protein-DNA interactions by surface plasmon resonance (SPR) microscopy. Both
      methods use streptavidin (SA) as a linker layer between a biotin-containing mixed
      self-assembled monolayer (SAM) and biotinylated dsDNAs to produce arrays with
      high packing density. The primary mixed SAM is produced from biotin- and
      oligo(ethylene glycol)-terminated thiols bonded as thiolates onto the gold
      surface. In the first method, a robotic microspotter is used to deliver nanoliter
      droplets of dsDNA solution onto a uniform layer of this SA ( approximately 2 x
      10(12) SA/cm(2)). SPR microscopy shows a density of (5-6) x 10(11) dsDNA/cm(2)
      (0.2-0.3 dsDNA/SA) in the array elements. The second method uses instead a
      microspotted array of this SA linker layer, onto which the microspots of dsDNA
      are added with spatial registry. SPR microscopy before addition of the dsDNA
      shows a SA coverage of 2 x 10(12) SA/cm(2) within the spots and a dsDNA density
      of 8.5 +/- 3.5 x 10(11) dsDNA/cm(2) (0.3-0.7 dsDNA/SA, depending on the length of
      dsDNA) after dsDNA spotting. We demonstrate the ability to simultaneously monitor
      protein binding with the SPR microscope in many 200-microm spots with 1-s time
      resolution and sensitivity to <1 pg of protein.

PMID- 14961722
TI  - Modifying the adsorption behavior of polyamidoamine dendrimers at silica surfaces
      investigated by total internal reflection fluorescence correlation spectroscopy.
AB  - Polyamidoamine (PAMAM) dendrimers were modified and tested for use as solution
      phase diffusion probes in silica nanostructures. In order for the successful
      application of dendrimers as solution-phase probes, their interactions with
      silica surfaces must be understood and controlled, so that the motion of the
      probe is not influenced by adsorption. Adsorption/desorption kinetics of PAMAM
      dendrimers and their diffusion in solution near silica surfaces were investigated
      with total internal reflection fluorescence correlation spectroscopy (TIR-FCS).
      Dendrimers of generations 3, 5, and 7 were dye-labeled with carboxyrhodamine 6G.
      Because PAMAM dendrimers are positively charged in solution (having primary
      amines as end groups), significant adsorption of these molecules to the
      negatively charged silica surface was observed. Adsorption/desorption rates and
      the equilibrium constant for adsorption were determined by fitting the
      autocorrelation functions to a kinetic model. The desorption rate decreases and
      the absorption equilibrium constant increases with higher dendrimer generation.
      To reduce the adsorption of these probes to silica surfaces, the labeled
      dendrimers were reacted with succinic anhydride, converting the primary amine end
      groups to negatively charged carboxylic acid groups. These carboxylated
      dendrimers did not detectably adsorb to silica from aqueous solution. TIR-FCS was
      used to determine their free-solution diffusion constants near silica surfaces,
      and the corresponding hydrodynamic radii compare favorably with values reported
      from forced Rayleigh scattering measurements.

PMID- 14961723
TI  - Poly(amidoamine) dendrimers as nanoscale diffusion probes in sol-gel films
      investigated by total internal reflection fluorescence spectroscopy.
AB  - Three generations of poly(amidoamine) dendrimers were dye-labeled and chemically
      modified to have terminal carboxyl groups and used as variably sized probes to
      study diffusion in thin sol-gel films. Total internal reflection fluorescence
      spectroscopy experiments, both correlation and concentration-jump measurements,
      were employed to measure the relative populations and effective diffusion
      coefficients of dendrimers in the films. For films prepared from small (27-nm)
      silica particles, larger dendrimers could be completely excluded from penetrating
      the sol-gel structure. In films made of larger (150-nm) particles with
      correspondingly larger pores, concentration-jump experiments showed that larger
      dendrimers are excluded from more of the intraparticle pore space than small
      dendrimers. Similarly, fluorescence-correlation measurements showed that the
      diffusion of smaller dendrimers exhibited greater tortuosity than larger
      dendrimers in the interparticle pores of the film. The smaller dendrimers explore
      a greater volume of smaller, more convoluted pores, whereas larger dendrimers
      penetrate a smaller volume of larger, more open pores.

PMID- 14961724
TI  - Reversible ratiometric probe for quantitative DNA measurements.
AB  - We have designed a reversible fluorescent DNA probe that can be used to determine
      the concentration of single-stranded DNA in solution by a ratiometric
      fluorescence measurement. The probe consists of a single-stranded dual
      fluorescently labeled DNA molecule that adopts a stem-loop conformation in its
      nonhybridized state. The stem length and the length of the loop region
      complementary to the target were chosen to allow for reversible binding. The
      excitation and emission wavelengths of the two labels Cy3 and Cy5 allow for
      fluorescence resonance energy transfer in the closed state. Upon hybridization,
      the probe opens up resulting in a fluorescence intensity increase of the donor
      and a fluorescence intensity decrease of the acceptor. The ratio of the acceptor
      to-donor fluorescence intensities is independent of the amount of probe and
      provides a quantitative measure of the free target concentration.

PMID- 14961725
TI  - Experimental proof of a chromatographic paradox: are the injected molecules in
      the peak?
AB  - Forty years ago Helfferich and Peterson published an article in Science regarding
      a "paradoxical" behavior in nonlinear chromatography (Helfferich, F.; Peterson,
      D. L. Science 1963, 142, 661-662). They theoretically predicted that when an
      excess of sample molecules is injected into a chromatographic column that is
      equilibrated with a constant stream of identical molecules, the observed peak
      will not contain the injected molecules. Instead the observed peak will only
      contain molecules from the stream whereas the injected molecules will exit the
      column in a slower moving, "invisible" peak. They considered it paradoxical that
      a single injection in a single-component system could cause the successive
      elution of two peaks (Helfferich, F. J. Chem. Educ. 1964, 41, 410-413). In this
      study, the paradox is experimentally proven for the first time. Two different
      strategies were employed: (i) a radiochemical approach and (ii) a method based on
      the use of two enantiomers in a nonchiral separation system. The experiments were
      compared with computer simulations.

PMID- 14961726
TI  - Analysis of saturated hydrocarbons by using chemical ionization combined with
      laser-induced acoustic desorption/Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - Laser-induced acoustic desorption (LIAD), combined with chemical ionization by
      the cyclopentadienyl cobalt radical cation (CpCo.+), is demonstrated to
      facilitate the analysis of saturated hydrocarbons by Fourier transform ion
      cyclotron resonance mass spectrometry. The LIAD/CpCo.+ method produces unique
      pseudomolecular ions for alkanes from C(24)H(50) to C(50)H(102). These alkanes
      were tested individually and in artificial mixtures of up to seven components.
      Only one product ion, [R + CpCo - 2H(2)].+, was detected for each alkane (R). The
      product ions' relative abundances correspond to the relative molar concentration
      of each alkane in mixtures. These findings provide a solid groundwork for the
      future application of this method for hydrocarbon polymer analyses.

PMID- 14961727
TI  - Ion-molecule reactions for mass spectrometric identification of functional groups
      in protonated oxygen-containing monofunctional compounds.
AB  - Protonated oxygen-containing monofunctional compounds react with selected
      methoxyborane reagents by proton transfer followed by nucleophilic substitution
      of methanol at the boron atom in a Fourier transform ion cyclotron resonance mass
      spectrometer. The derivatized oxygen functionality can be identified by H/D
      exchange, collision-activated dissociation, or both. This information on the
      identity of the functionalities in the analyte, in conjunction with molecular
      formula information obtained from exact mass measurements on either the
      protonated or derivatized analyte, facilitates structure elucidation of unknown
      organic compounds in a mass spectrometer.

PMID- 14961728
TI  - Single-component shock layer analysis in elution chromatography.
AB  - One of the fundamental results of the theory of nonlinear chromatography is that
      a propagation velocity is associated with each concentration. This velocity is
      related to the slope of the isotherm at the corresponding concentration. It
      follows that if a continuous concentration gradient is injected into a column,
      the gradient profile will not propagate in a mere translation but will
      progressively change shape. In the most common case of a convex upward isotherm
      (e.g., Langmuir), a linear gradient will become curved upward, the high
      concentrations migrating faster than the low ones. However, high concentrations
      cannot pass low ones, so the concentrations pile up, a concentration shock forms,
      and its height increases. In practice, axial dispersion and the mass-transfer
      resistances combine and prevent the formation of a true shock. A shock layer, a
      region where the concentration gradient is very steep, is formed. This shock
      layer migrates at the same velocity as the ideal shock would. Many
      characteristics of concentration shocks and shock layers have been determined
      previously, but not the time that it takes for a continuous gradient to turn into
      a shock layer, the circumstances of the birth of the shock layer, and of its
      growth. Yet, this is important to know to understand certain aspects of gradient
      elution. We have derived simple equations relating the circumstances of the birth
      of shocks to the phase equilibrium isotherm and to the column characteristics.
      The results of experimental measurements made with a high-efficiency analytical
      column are in excellent agreement with these theoretical predictions.

PMID- 14961729
TI  - Detection of methamphetamine in the presence of nicotine using in situ chemical
      derivatization and ion mobility spectrometry.
AB  - The detection of methamphetamine in the presence of nicotine has been
      successfully accomplished using in situ chemical derivatization with propyl
      chloroformate as the derivatization reagent and ion mobility spectrometry (IMS).
      The rapid detection of methamphetamine is important for forensic scientists in
      order to establish a chain of evidence and link criminals to the crime scene.
      Nicotine is pervasive in clandestine drug laboratories from cigarette smoke
      residue. It has been demonstrated that nicotine obscures the methamphetamine
      peaks in ion mobility spectrometers due to their similar charge affinities and
      ion mobilities, which makes their detection a challenging task. As a consequence,
      false positive or negative responses may arise. In situ chemical derivatization
      poses as a sensitive, accurate, and reproducible alternative to remove the
      nicotine background when detecting nanogram amounts of methamphetamine. The
      derivatization agent was coated onto the sample disk, and the derivatization
      product corresponding to propyl methamphetamine carbamate was detected. In the
      present study, in situ chemical derivatization was demonstrated to be a feasible
      method to detect methamphetamine hydrochloride as the carbamate derivative, which
      was baseline-resolved from the nicotine peak. Alternating least squares (ALS) was
      used to model the datasets. A mixture containing both compounds revealed reduced
      mobilities of 1.61 cm(2)/V.s and 1.54 cm(2)/V.s for methamphetamine and nicotine,
      respectively. The reduced mobility of propyl methamphetamine carbamate was found
      at 1.35 cm(2)/V.s.

PMID- 14961730
TI  - Combining liquid chromatography with MALDI mass spectrometry using a heated
      droplet interface.
AB  - A novel interfacing technology is described to combine solution-based separation
      techniques such as liquid chromatography (LC) with matrix-assisted laser
      desorption ionization (MALDI) mass spectrometry. The interface includes a
      transfer tube having an inlet and an outlet, the inlet being adapted to accept
      the LC effluents and the outlet being adapted to form continuously replaced,
      hanging droplets of the liquid stream, and a MALDI sample plate mounted below the
      outlet of the transfer tube for collecting the droplets. The liquid stream in the
      transfer tube is heated to a temperature sufficient to cause partial evaporation
      of the carrier solvent from the hanging droplets. The droplets are dislodged to
      the MALDI plate, which is heated to above the boiling point of the carrier
      solvent to cause further evaporation of the carrier solvent from the collected
      droplets. It is found that analytes can be fractionated and deposited to a sample
      spot of 0.8 mm in diameter when a liquid flow rate of up to 50 microL/min and a
      fractionation interval of 1 min/spot are used. Flow rate of up to 200 microL/min
      can be used with a deposition sample spot of 2.4 mm in diameter on a commercial
      MALDI target. This heated droplet interface does not introduce sample loss, and
      the detection sensitivity of LC/MALDI is similar to that of standard MALDI, i.e.,
      low femtomoles for peptide analysis with a microliter sample deposition. It is
      compatible with microbore and narrow-bore column separation, thus allowing the
      injection of a larger amount of sample for separation and analysis, compared to a
      capillary column LC/MALDI system. The detection dynamic range is shown to be in
      the order of 10(6) for peptide mixture analysis, which is 4 orders of magnitude
      greater than standard MALDI. The application of this interface for combining LC
      with MALDI MS/MS is demonstrated in the proteome analysis of water-soluable
      protein components of E. coli K12 extracts.

PMID- 14961731
TI  - Relative quantitation of intact proteins of bacterial cell extracts using
      coextracted proteins as internal standards.
AB  - A method for quantitating protein expression using LC/MS of whole proteins is
      described. This method is based on the fact that some proteins present in cells
      are abundant universal proteins whose expression levels exhibit little variation.
      This method demonstrates that these coextracted proteins can be used as internal
      standards to which the other proteins in the sample can be compared. By comparing
      the intensities of a selected protein to marker proteins, or internal standards,
      a relative ratio is obtained. This ratio can then be used to determine the
      relative amount of protein expression between cellular extracts. The validity of
      this approach is described for a standard protein mixture, as well as, E. coli
      cells that were known to differentially express green fluorescent protein.

PMID- 14961732
TI  - Development and evaluation of a candidate reference method for the determination
      of total cortisol in human serum using isotope dilution liquid
      chromatography/mass spectrometry and liquid chromatography/tandem mass
      spectrometry.
AB  - Cortisol is an important diagnostic marker for the production of steroid
      hormones, and accurate measurements of serum cortisol are necessary for proper
      diagnosis of adrenal function. A candidate reference method involving isotope
      dilution coupled with liquid chromatography/mass spectrometry (LC/MS) and liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) has been developed and
      critically evaluated. An isotopically labeled internal standard, cortisol-d(3),
      was added to serum, followed by equilibration and solid-phase and ethyl acetate
      extractions to prepare samples for liquid chromatography/mass spectrometry
      electrospray ionization (LC/MS-ESI) and liquid chromatography/tandem mass
      spectrometry electrospray ionization (LC/MS/MS-ESI) analyses. (M + H)(+) ions at
      m/z 363 and 366 for cortisol and its labeled internal standard were monitored for
      LC/MS. The transitions of (M + H)(+) --> [(M + H)(+) - 2H(2)O] at m/z 363 --> 327
      and 366 --> 330 were monitored for LC/MS/MS. The accuracy of the measurement was
      evaluated by a comparison of results of this candidate reference method on
      lyophilized human serum reference materials for cortisol [Certified Reference
      Materials 192 and 193] with the certified values determined by gas
      chromatography/mass spectrometry reference methods and by a recovery study for
      the added cortisol. The results of this method for total cortisol agreed with the
      certified values within 1.1%. The recovery of the added cortisol ranged from
      99.8% to 101.0%. This method was applied to the determination of cortisol in
      samples of frozen serum pools. Excellent precision was obtained with within-set
      CVs of 0.3%-1.5% and between-set CVs of 0.04%-0.4% for both LC/MS and LC/MS/MS
      analyses. The correlation coefficients of all linear regression lines ranged from
      0.998 to 1.000. The detection limits (at a signal-to-noise ratio of approximately
      3-5) were 10 and 15 pg for LC/MS and LC/MS/MS, respectively. This method, which
      demonstrates good accuracy and precision, and is free from interferences from
      structural analogues, qualifies as a candidate reference method and can be used
      as an alternative reference method to provide an accuracy base to which the
      routine methods can be compared.

PMID- 14961733
TI  - Immobilized DNA aptamers as target-specific chiral stationary phases for
      resolution of nucleoside and amino acid derivative enantiomers.
AB  - Recently, we described the use of a DNA aptamer as a new target-specific chiral
      stationary phase (CSP) for the separation of oligopeptide enantiomers (Michaud,
      M.; Jourdan, E.; Villet, A.; Ravel, A.; Grosset, C.; Peyrin, E. J. Am. Chem. Soc.
      2003, 125, 8672). However, from a practical point of view, it was fundamental to
      extend the applicability of such target-specific aptamer CSP to the resolution of
      small (bioactive) molecule enantiomers. In this paper, immobilized DNA aptamers
      specifically selected against D-adenosine and L-tyrosinamide were used to resolve
      the enantiomers by HPLC, using microbore columns. At 20 degrees C, the adenosine
      enantioseparation was similar to that classically reported with imprinted CSPs
      (approximately 3.5) while a very high enantioselectivity was observed for the
      tyrosinamide enantiomers (the nontarget enantiomer was essentially nonretained on
      the CSP). The influence of temperature on solute binding and chiral
      discrimination was analyzed. The binding enthalpic contributions were determined
      from linear van't Hoff plots. Very large DeltaH values were obtained for the
      target enantiomers (-71.4 +/- 0.7 kJ/mol for D-adenosine and -139.4 +/- 2.0
      kJ/mol for L-tyrosinamide). Such values were consistent with the formation of a
      tight complex between these analytes and the aptamer CSPs. This work demonstrates
      that target-specific aptamer CSPs constitute a powerful tool for the resolution
      of small (bioactive) molecule enantiomers.

PMID- 14961734
TI  - Development of direct ELISA for the determination of 4-nonylphenol and
      octylphenol.
AB  - Development of direct competitive enzyme-linked immunoadsorbent assays (ELISAs)
      based on polyclonal and monoclonal antibodies raised against 4-n-alkylphenol
      hapten mimics is described. A strong tendency to recognize 4-nonylphenol (NP) and
      4-octylphenol (OP) as a total analyte amount was indicated by cross-reactivity
      pattern established for two polyclonal antibodies. These antibodies were employed
      for development of class-selective assays exhibiting IC(50) values around 40
      microg.L(-1) for technical 4-NP. Specificity of the monoclonal antibody 4H6 and
      additional two polyclonal antibodies allowed sensitive detection of linear long
      chain forms of 4-n-alkylphenols (4-n-AP). The assays incorporating these
      antibodies offer a potential for detecting the minor fraction of NP/OP isomer
      spectrum having IC(50) = 11.5 microg.L(-1) for 4-n-NP. No cross-reactivity
      interference was indicated for linear alkylbenzene sulfonates and phenolic
      compounds. To interpret the measured data in terms of analytical equivalents, a
      reliable relationship between the assay responses and AP content of contaminated
      samples should be verified and validated.

PMID- 14961735
TI  - In situ derivatization/solid-phase microextraction: determination of polar
      aromatic amines.
AB  - A solid-phase microextraction GC/MS method for the trace determination of a wide
      variety of polar aromatic amines in aqueous samples was developed. Prior to
      extraction the analytes were derivatized directly in the aqueous solution by
      diazotation and subsequent iodination in a one-pot reaction. The derivatives were
      extracted by direct-SPME using a PDMS/DVB fiber and analyzed by GC/MS in the full
      scan mode. By diazotation/iodination, the polarity of the analytes was
      significantly decreased and as a consequence extraction yields were dramatically
      improved. The derivatization proved to be suitable for strongly deactivated
      aromatic amines and even the very polar diamino compounds can efficiently be
      enriched after derivatization. We investigated 18 anilines comprising a wide
      range of functional groups, which could be determined simultaneously. The method
      was thoroughly validated, and the precision at a concentration of 0.5 microg/L
      was 3.8-11% relative standard deviation for nonnitrated analytes using aniline
      d(5) as internal standard and 3.7-10% for nitroaromatic amines without internal
      standard. The in situ derivatization/SPME/GC/MS method was calibrated over the
      whole analytical procedure and was linear over 2 orders of magnitude. Using 10-mL
      samples, detection limits of 2-13 ng/L were achieved for 15 of the 18 analytes.
      For two aminodinitrotoluene isomers and a diaminonitrotoluene, detection limits
      ranged from 27 to 38 ng/L. By allowing quantification at the 0.1 microg/L level,
      analysis of all target compounds meets EU drinking water regulations. The method
      provides high sensitivity, robustness, and high sample throughput by automation.
      Finally, the method was applied to various real water samples and in wastewater
      from a former ammunition plant the contents of several aromatic amines were
      quantified.

PMID- 14961736
TI  - Radio frequency glow discharge-optical emission spectrometry for direct
      quantitative analysis of glass.
AB  - Direct solid quantitative analysis of glass by radio frequency (rf) glow
      discharge-optical emission spectrometry (GD-OES) by using special silicate
      glasses of very different composition (e.g., the SiO(2) content varied from 10 to
      70%, the CaO content from 0 to 25%, the Na(2)O content from 0 to 15%, the K(2)O
      content from 0 to 19%, etc.) for calibration is investigated in detail. The
      effect of sample thickness is studied by using calibration standards and samples
      of different thickness than that considered as "standard" in our experiments (3
      mm). Considering the variable concentrations of easily ionized elements present
      in the different glass specimens, measurements of the Mg(II) 280.27-nm/Mg(I)
      285.21-nm line intensity ratio for the calibration standards and samples
      containing magnesium were carried out to check the plasma robustness. Results
      showed that this indicator value remained virtually constant for all the glasses
      assayed. The proposed quantification scheme is based on the "constant emission
      yield" concept in which the measured analytical signals were corrected for
      thickness differences relative to the 3-mm "standard thickness". In addition,
      better fittings to linear plots were obtained when using discharge Ar emissions
      as the reference signal. Results for the simultaneous determination of the glass
      major components (SiO(2), Na(2)O, CaO, MgO, Al(2)O(3), and K(2)O) by rf-GD-OES in
      two samples of different thickness (3 and 1.1 mm) showed good agreement with the
      expected results.

PMID- 14961737
TI  - Mass analysis of water-soluble polymers by mobility measurement of charge-reduced
      ions generated by electrosprays.
AB  - Aqueous solutions of poly(ethylene glycol) (PEG) in a 10 mM ammonium acetate
      buffer are electrosprayed, and the maximum charge state on the resulting gas
      phase ions is reduced to unity using a radioactive source. The mobility
      distribution of these charged particles is then measured in air in a differential
      mobility analyzer of unusually high resolution. The relation Z(m) between the
      mobility Z of a polymer molecule and its mass m is determined by means of
      narrowly distributed PEG mass standards. The molecular weight range of available
      standards is extended by generating clusters containing from one up to six
      molecules of the primary PEG standard. The mass at the peak of the distribution
      of the lowest standard (PEG-4k) is determined by MALDI mass spectrometry and
      agrees with the manufacturer's value and previous MALDI literature data. The
      masses for the 50K and 120K standards are found to differ by 8.6 and 6.6%,
      respectively, from the manufacturer's value. Using known relationships, the
      particle diameter d of the ions is calculated from the measured mobility. Plots
      of d versus m(1/3) give straight lines over the full mass range studied (4000-700
      000 Da, particle diameter from 3 to 12 nm), indicating that these PEG particles
      are indeed spherical and have a density rho independent of size. The slope of the
      d versus m(1/3) curve provides a density rho = 1.25 g/cm(3), close to the known
      bulk density, rho(PEG) = 1.21 g/cm(3).

PMID- 14961738
TI  - Development of a solid-phase microextraction gas chromatography/tandem mass
      spectrometry method for polybrominated diphenyl ethers and polybrominated
      biphenyls in water samples.
AB  - Solid-phase microextraction has been applied for the first time to the
      determination of trace concentrations of some brominated flame-retardant
      compounds (BFRs) in water samples. For the development of the method, six
      polybrominated diphenyl ethers and two polybrominated biphenyls were considered
      as target analytes. The factors expected to influence the extraction process are
      fully discussed. Quantification has been performed by gas chromatography/tandem
      mass spectrometry using an ion trap mass analyzer. This is also the first time
      that tandem mass spectrometry is applied with these analytes. Unlike conventional
      methods for BFR analysis, which involve solvent extraction and several cleanup
      steps before gas chromatography, the proposed method uses headspace extraction
      and hard contamination of the chromatographic system is prevented. In addition,
      tandem mass spectrometry provides selectivity and sensitivity in the detection
      process. The method performs well achieving good linearity (R(2) > 0.997),
      precision, and detection limits (S/N = 3) ranging from 7.5 to 190 pg/L. The
      method has been applied to a variety of water samples.

PMID- 14961739
TI  - Liquid chromatography/coordination ion spray-mass spectrometry for the analysis
      of rubber vulcanization products.
AB  - Liquid chromatography/coordination ion spray-mass spectrometry has been used for
      the identification of reaction products in a model rubber vulcanization process.
      After LC separation using reversed-phase conditions, AgBF(4) in acetonitrile was
      added, and strong signals were observed for silica-rubber coupling agents and
      products of the reaction between these and alkenes. The method performs best for
      substances containing sulfur chains with chain lengths between two and eight
      sulfur atoms, but sulfur-free compounds containing triethoxysilyl groups were
      detected as well. For the latter, the postcolumn addition of NaBF(4) proved to be
      a suitable alternative. Besides the coupling agents, various reaction products,
      including sulfur-chain bridged alkenes were identified.

PMID- 14961740
TI  - Nonlinear wavelet compression of ion mobility spectra from ion mobility
      spectrometers mounted in an unmanned aerial vehicle.
AB  - Linear and nonlinear wavelet compression of ion mobility spectrometry (IMS) data
      are compared and evaluated. IMS provides low detection limits and rapid response
      for many compounds. Nonlinear wavelet compression of ion mobility spectra reduced
      the data to 4-5% of its original size, while eliminating artifacts in the
      reconstructed spectra that occur with linear compression, and the root-mean
      square reconstruction error was 0.17-0.20% of the maximum intensity of the
      uncompressed spectra. Furthermore, nonlinear wavelet compression precisely
      preserves the peak location (i.e., drift time). Small variations in peak location
      may occur in the reconstructed spectra that were linearly compressed. A method
      was developed and evaluated for optimizing the compression. The compression
      method was evaluated with in-flight data recorded from ion mobility spectrometers
      mounted in an unmanned aerial vehicle (UAV). Plumes of dimethyl methylphosphonate
      were disseminated for interrogation by the UAV-mounted IMS system. The daublet 8
      wavelet filter exhibited the best performance for these evaluations.

PMID- 14961741
TI  - Direct from polyacrylamide gel infrared laser desorption/ionization.
AB  - The direct combination of gel electrophoresis and infrared laser
      desorption/ionization time-of-flight mass spectrometry has been demonstrated. We
      present results for infrared laser desorption and ionization mass spectrometry of
      peptides and proteins directly from a polyacrylamide gel without the addition of
      a matrix. Analyte molecules up to 6 kDa were ionized directly from a vacuum-dried
      sodium dodecyl sulfate-polyacrylamide gel after electrophoretic separation. Mass
      spectra were obtained at the wavelength of 2.94 microm, which is consistent with
      IR absorption by N-H and O-H stretch vibrations of water and other constituents
      of the gel. A 5-nmol quantity of peptide or protein was loaded per gel slot,
      although it was possible to obtain mass spectra from a small fraction of the gel
      spot. This technique shows promise for the direct identification of both parent
      and fragment masses of proteins contained in polyacrylamide gels.

PMID- 14961742
TI  - Electrochemical biosensing platforms using platinum nanoparticles and carbon
      nanotubes.
AB  - Platinum nanoparticles with a diameter of 2-3 nm were prepared and used in
      combination with single-wall carbon nanotubes (SWCNTs) for fabricating
      electrochemical sensors with remarkably improved sensitivity toward hydrogen
      peroxide. Nafion, a perfluorosulfonated polymer, was used to solubilize SWCNTs
      and also displayed strong interactions with Pt nanoparticles to form a network
      that connected Pt nanoparticles to the electrode surface. TEM and AFM micrographs
      illustrated the deposition of Pt nanoparticles on carbon nanotubes whereas cyclic
      voltammetry confirmed an electrical contact through SWCNTs between Pt
      nanoparticles and the glassy carbon (GC) or carbon fiber backing. With glucose
      oxidase (GOx) as an enzyme model, we constructed a GC or carbon fiber
      microelectrode-based biosensor that responds even more sensitively to glucose
      than the GC/GOx electrode modified by Pt nanoparticles or CNTs alone. The
      response time and detection limit (S/N = 3) of this biosensor was determined to
      be 3 s and 0.5 microM, respectively.

PMID- 14961743
TI  - Characterization of carbon/nitroazobenzene/titanium molecular electronic
      junctions with photoelectron and Raman spectroscopy.
AB  - Molecular junctions consisting of nitroazobenzene (NAB) chemisorbed to a
      substrate of pyrolyzed photoresist film (PPF) and a top contact of vapor
      deposited titanium were examined with Raman spectroscopy and X-ray photoelectron
      spectroscopy (XPS). The thickness of the NAB layer varied from submonolayer to
      4.5 nm, and a thin (1-3 nm) overlayer of Ti was deposited by electron beam
      deposition. Without Ti, the NAB surface Raman spectrum was sufficiently strong to
      observe previously unreported modes in the 500-1000-cm(-1) region, and the 1000
      1700-cm(-1) region was sufficiently strong to observe the effects of metal
      deposition. Upon Ti deposition, the intensities of NAB modes associated with the
      nitro group decreased significantly, and the XPS indicated formation of a Ti-N
      bond. For the thicker NAB layers (1.9 and 4.5 nm), the intensities of the NO(2)
      Raman modes partially recovered over a several-day period, but they remain
      depressed or absent in the submonolayer sample. The results indicate a reaction
      between condensing Ti atoms and the terminal NO(2) group, probably to form a Ti
      nitroso linkage between NAB and Ti. The result is a molecular junction with
      covalent bonding at both ends in the form of a C-C bond between PPF and NAB and a
      Ti-N bond to the top contact. The structural implications of the current results
      are interpreted in the context of recently reported functioning PPF/NAB/Ti
      molecular electronic junctions. In particular, the reaction between Ti and the
      nitro group appears to prevent short circuits resulting from incursion of Ti into
      the NAB layer.

PMID- 14961744
TI  - Acetylcholine and choline amperometric enzyme sensors characterized in vitro and
      in vivo.
AB  - Acetylcholine (ACh) and choline (Ch) are important neuroactive molecules, yet
      detection of these substances in vivo presents significant analytical challenges.
      New multienzyme amperometric biosensors are presented here with measurement of
      physiologically relevant levels of ACh and Ch in vivo. Poly(m-(1,3)
      phenylenediamine) (pmPD) electropolymerized on a platinum iridium wire (Pt)
      served as a template for immobilization of enzymes. A multienzyme layer
      containing choline oxidase (ChOx) and ascorbic acid oxidase (AAO) for a Ch sensor
      or ChOx, acetylcholinesterase (AChE), and AAO for a ACh/Ch sensor was immobilized
      with bovine serum albumin by cross-linking with glutaraldeyhyde. The pmPD enzyme
      sensors displayed enhanced sensitivity, stability, and selectivity compared to
      the same multienzyme systems immobilized to solvent cast Nafion and cellulose
      acetate-modified Pt. Sensor response was linear up to 100 microM ACh or Ch.
      Detection limits were 0.66 +/- 0.46 microM ACh and 0.33 +/- 0.09 microM Ch, and
      response times were <1 s. Selectivity for Ch and ACh relative to potential
      interferences and pharmacological agents commonly used to examine cholinergic
      physiology was demonstrated. Temperature and pH dependence and the effect of
      storage conditions on sensor sensitivity and selectivity were determined.
      Exogenous and endogenous Ch and ACh were measured in the rat brain in vivo.

PMID- 14961745
TI  - Interdigitated Array microelectrode-based electrochemical impedance immunosensor
      for detection of Escherichia coli O157:H7.
AB  - A label-free electrochemical impedance immunosensor for rapid detection of
      Escherichia coli O157:H7 was developed by immobilizing anti-E. coli antibodies
      onto an indium-tin oxide interdigitated array (IDA) microelectrode. Based on the
      general electronic equivalent model of an electrochemical cell and the behavior
      of the IDA microelectrode, an equivalent circuit, consisting of an ohmic resistor
      of the electrolyte between two electrodes and a double layer capacitor, an
      electron-transfer resistor, and a Warburg impedance around each electrode, was
      introduced for interpretation of the impedance components of the IDA
      microelectrode system. The results showed that the immobilization of antibodies
      and the binding of E. coli cells to the IDA microelectrode surface increased the
      electron-transfer resistance, which was directly measured with electrochemical
      impedance spectroscopy in the presence of [Fe(CN)(6)](3-/4-) as a redox probe.
      The electron-transfer resistance was correlated with the concentration of E. coli
      cells in a range from 4.36 x 10(5) to 4.36 x 10(8) cfu/mL with the detection
      limit of 10(6) cfu/mL.

PMID- 14961746
TI  - Quantitative X-ray photoelectron spectroscopy and time-of-flight secondary ion
      mass spectrometry characterization of the components in DNA.
AB  - The great diversity of techniques to synthesize and use DNA microarrays has made
      them extremely flexible for a variety of applications. This flexibility also has
      made standardization difficult, leading to problems comparing data from these
      different systems. In this work, we use the surface science techniques of X-ray
      photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass
      spectrometry (TOF-SIMS) to analyze the components of DNA. The atomic ratios of
      the components of nucleobases, nucleosides, and nucleotides were characterized by
      XPS. The chemical shifts in the high-resolution XPS spectra allow for their
      relatively easy resolution. The unique positive and negative ions from the
      nucleobases, nucleosides, and nucleotides in their TOF-SIMS spectra were
      identified. This information was used to build a comprehensive table of all of
      the molecular ions. These standard spectra of DNA components can be used to
      predict the relative amounts of the bases within more complex molecules either by
      univariate analysis (i.e., by relating the base molecular ions to the sugar
      fragment ions within the nucleotides) or by multivariate analysis (e.g.,
      principal component analysis). Our preliminary examination of four
      oligonucleotides shows promising results in that we can distinguish between two
      oligomers of similar composition using univariate and multivariate analysis,
      although additional studies are needed to expand this method to more complex
      oligomers.

PMID- 14961747
TI  - Characterization of the imprint effect and the influence of imprinting conditions
      on affinity, capacity, and heterogeneity in molecularly imprinted polymers using
      the Freundlich isotherm-affinity distribution analysis.
AB  - Molecularly imprinted polymers (MIPs) have been used in a wide range of
      analytical applications in particular in chromatography and sensing. However, the
      binding properties in MIPs are typically measured only in a narrow concentration
      range, which corresponds to only a subset of the sites in MIPs. This limited
      analytical window and binding site heterogeneity of MIPs leads to inaccuracies
      and inconsistencies in the estimation of their binding properties. This has
      hampered the characterization and optimization of MIPs for analytical
      applications. In this study, the origins of the molecular imprinting effect were
      studied using the newly developed Freundlich isotherm-affinity distribution
      (FIAD) analysis. The analysis is able to readily calculate an affinity
      distribution for MIPs from the limited analytical window. The FIAD analysis also
      yields an estimate of number, affinity, and heterogeneity for this subset of
      binding sites. Consistent with previous studies, MIPs were found to have higher
      capacities than the corresponding nonimprinted polymers (NIPs). Interestingly,
      MIPs were also found to be more heterogeneous than NIPs. Examination of variables
      in the imprinting process including temperature, template concentration, and
      cross-linking percentages further confirmed these trends. Based on these
      observations, a model for the imprinting effect was developed. The larger
      population of high-affinity sites in MIPs appears to arise from a broadening of
      the heterogeneous distribution. This suggests that noncovalent MIPs may be ill
      suited for chromatographic applications and other applications that are
      detrimentally affected by binding site heterogeneity and better suited to
      applications that are less affected by heterogeneity such as sensing.

PMID- 14961748
TI  - Ultra-high-efficiency strong cation exchange LC/RPLC/MS/MS for high dynamic range
      characterization of the human plasma proteome.
AB  - High-efficiency nanoscale reversed-phase liquid chromatography (chromatographic
      peak capacities of approximately 1000: Shen, Y.; Zhao, R.; Berger, S. J.;
      Anderson, G. A.; Rodriguez, N.; Smith, R. D. Anal. Chem. 2002, 74, 4235. Shen,
      Y.; Moore, R. J.; Zhao, R.; Blonder, J.; Auberry, D. L.; Masselon, C.; Pasa
      Tolic, L.; Hixson, K. K.; Auberry, K. J.; Smith, R. D. Anal. Chem. 2003, 75,
      3596.) and strong cation exchange LC was used to obtain ultra-high-efficiency
      separations (combined chromatographic peak capacities of >10(4)) in conjunction
      with tandem mass spectrometry (MS/MS) for characterization of the human plasma
      proteome. Using conservative SEQUEST peptide identification criteria (i.e.,
      without considering chymotryptic or elastic peptides) and peptide LC normalized
      elution time constraints, the separation quality enabled the identification of
      proteins over a dynamic range of greater than 8 orders of magnitude in relative
      abundance using ion trap MS/MS instrumentation. Between 800 and 1682 human
      proteins were identified, depending on the criteria used for identification, from
      a total of 365 microg of human plasma. The analyses identified relatively low
      level (approximately pg/mL) proteins (e.g., cytokines) coexisting with high
      abundance proteins (e.g., mg/mL-level serum albumin).

PMID- 14961749
TI  - Integrating histology and imaging mass spectrometry.
AB  - MALDI (matrix-assisted laser desorption/ionization) imaging mass spectrometry
      (IMS) is a new technology that generates molecular profiles and two-dimensional
      ion density maps of peptide and protein signals directly from the surface of thin
      tissue sections. This allows specific information to be obtained on the relative
      abundance and spatial distribution of proteins. One important aspect of this is
      the opportunity to correlate these specific ion images with histological features
      observed by optical microscopy. To facilitate this, we have developed protocols
      that allow MALDI mass spectrometry imaging and optical microscopy to be performed
      on the same section. Key components of these protocols involve the use of
      conductive glass slides as sample support for the tissue sections and MS-friendly
      tissue staining protocols. We show the effectiveness of these with protein
      standards and with several types of tissue sections. Although stain-specific
      intensity variations occur, the overall protein pattern and spectrum quality
      remain consistent between stained and control tissue samples. Furthermore,
      imaging mass spectrometry experiments performed on stained sections showed good
      image quality with minimal delocalization of proteins resulting from the staining
      protocols.

PMID- 14961750
TI  - Unimolecular beacons for the detection of DNA-binding proteins.
AB  - A new methodology for detecting sequence-specific DNA-binding proteins has been
      recently developed (Heyduk, T.; Heyduk, E. Nat. Biotechnol. 2002, 20, 171). The
      core feature of this methodology is protein-dependent association of two
      fluorochrome-labeled DNA fragments, which allows generation of a fluorescence
      signal reporting the presence of the target protein. Previous kinetic experiments
      identified the association of the two DNA fragments as the rate-limiting step of
      the assay. Here we report on a variant of the assay, in which components of the
      assay--fluorescent DNA fragments--were covalently tethered by a non-DNA linker
      with the goal of increasing the rate of association of the two fragments. We
      investigated the effect of the tether on the performance of the assay under a
      variety of conditions using a model DNA-binding protein. Quantitative titrations
      and rapid kinetic stopped-flow experiments were conducted to validate the
      molecular model that describes the two linked equilibria: oscillation of the
      tethered construct between the open and closed states and the exclusive
      association of the protein with the closed state. Experiments were also performed
      to demonstrate the ability of these tethered constructs to signal when attached
      to a solid surface. The major advantage of this new assay format is the faster
      response time for the detection allowing the higher throughput of the analysis.
      Additionally, it will be possible to attach tethered beacons to other solid
      surfaces, thus allowing the preparation of arrays containing molecular beacons
      for many different DNA-binding proteins.

PMID- 14961751
TI  - Nanoelectrospray ionization of protein mixtures: solution pH and protein pI.
AB  - Solutions consisting of single proteins and mixtures of proteins at different pH
      values have been subjected to both positive ion and negative ion nanoelectrospray
      ionization to study the influence of solvent pH and protein pI on the ionization
      responses of proteins. As has been noted previously, it is possible to form
      protein ions of one polarity despite the fact that the proteins are present as
      the opposite polarity in solution. However, total response under this condition
      tends to be at least an order of magnitude less than the condition in which the
      nanoelectrospray ionization polarity is the same as the net charge of the
      proteins in solution. Furthermore, maximum signals in positive ion mode were
      noted when the pH value of the solution was 4-5 units lower than the protein pI.
      In the negative ion mode, maximum protein anion signals were observed when the pH
      was roughly 5 units higher than the protein pI. While only small changes in the
      abundance-weighted average charge were noted as a function of solution
      conditions, the extent of sodium ion incorporation was seen to depend strongly on
      the relationship between net protein charge in solution and gas-phase ion
      polarity. Sodium ion incorporation was minimized under conditions of maximum
      signal (i.e., low pH positive ion mode and high pH negative ion mode). Sodium ion
      incorporation was highest when the protein ion polarities in solution and the gas
      phase were opposite. These observations are consistent with the charged residue
      model for electrospray ionization and suggest that a degree of selectivity for
      electrospray ionization applied to protein mixtures can be realized via judicious
      selection of solution pH and ionization polarity. Furthermore, the relative
      extent of sodium ion incorporation under a given set of conditions appears to
      correlate, at least qualitatively, with protein pI.

PMID- 14961752
TI  - A packaging technique for polymer microfluidic platforms.
AB  - A new technique, resin-gas injection, has been developed for bonding and surface
      modification of polymer microfluidic devices. This method can easily bond
      biochips with complex flow patterns. A cascade micromixer and a multichannel DNA
      sequencing chip were demonstrated experimentally. By adding surface modification
      agents, the interfacial free energy of the substrate with water can be
      controlled. Local modification of the channel surface can also be achieved
      through sequential resin-gas injection in conjunction with a masking technique.
      For application, this technique is used to form a layer of dry monolithic
      stationary hydrogel on the walls of a microchannel, serving as a sieving material
      for electrophoresis separation of DNA fragments. The reagent loading and the
      electrophoresis separation efficiency of this technique were compared
      experimentally with the conventional linear polymer solution method used in the
      microchannel-based DNA sequencing process. It is found that our method has the
      advantages of more user-friendly operation, easier and faster sample loading, but
      slightly less separation efficiency.

PMID- 14961753
TI  - Polarimetric assay for the medium-throughput determination of alpha-amino acid
      racemase activity.
AB  - A polarimetric assay has been developed for the identification of alpha-amino
      acid racemase activity. The setup consists of a microcuvette polarimeter (40
      microL volume) connected to a pipetting robot for microtiter plates, a pump, and
      data processing. It could be demonstrated for a glutamate racemase from
      Lactobacillus fermentii, expressed in Escherichia coli, serving as model enzyme,
      that its activity can be determined from the time-dependent change of the optical
      rotation using l-glutamate as substrate. Thus, the specific activity was
      determined to 111.4 mdeg/min which corresponds to 45.7 micromol/min per mg
      purified enzyme. Moreover, a protocol was developed that allows the measurement
      of racemase activity from 96-well microtiter plates using purified enzymes. Thus,
      the method described can be used to determine racemase activity in an automatic
      manner. It should be also applicable for the screening of enzyme libraries
      created by directed evolution.

PMID- 14961754
TI  - Device for the reversed-phase separation and on-target deposition of peptides
      incorporating a hydrophobic sample barrier for matrix-assisted laser
      desorption/ionization mass spectrometry.
AB  - The separation of peptide mixtures from proteolytic cleavage is often necessary
      prior to mass spectrometry (MS) to enhance sensitivity and peptide mapping
      coverage. When buffers, salts, and other higher abundance peptides/contaminants
      are present, competition for charge during the electrospray ionization and matrix
      assisted laser desorption/ionization (MALDI) processes can lead to ion
      suppression for the targeted analyte(s). In this note, a simple reversed-phase
      microcolumn sample separation and deposition device (Sep-Dep) is described. The
      use of this device improves or renders possible the analysis of complex or
      contaminated peptide mixtures by MALDI-MS. The method is simple and inexpensive
      and utilizes single-use low-cost Geloader-type columns packed with reversed-phase
      material. The device described utilizes an open column, allowing for a gradient
      or narrow-step gradient to be applied by any solvent delivery system or manually
      with a pipet. A key feature of the device is a deposition chamber that can be
      custom-built to hold any MALDI target. The Sep-Dep device is attached directly to
      an in-house vacuum line and draws solvent from the open-ended LC column. The
      elution of separated peptides is performed directly onto a target that has been
      treated with a hydrophobic barrier. This barrier effectively isolates fractions
      and improves the quality and morphology of the matrix crystals. The method
      produces efficient separations of proteolytic peptides, significantly reducing
      signal suppression effects in MALDI.

PMID- 14961755
TI  - Development of a hyphenated microanalytical system for the investigation of
      leaching kinetics of heavy metals in environmental samples.
AB  - A fast and convenient method for on-line monitoring of the extraction of heavy
      metals from solid (environmental) matrixes was developed. By the incorporation of
      microcartridges filled with dried and pulverized solid samples into the conduits
      of a flow system and appropriate selection of the liquid flowing through the
      cartridge, information about the degree of leaching and in particular of the
      kinetics of the leaching process are obtained. The method was optimized for
      determination of different metals of environmental concern using in-line
      detection by FAAS and ICPMS.

PMID- 14961756
TI  - Membrane-based parallel plate denuder for the collection and removal of soluble
      atmospheric gases.
AB  - A continuously wetted cellulose acetate membrane-based parallel plate diffusion
      denuder is described. This is the first membrane-based denuder that has a small
      enough internal liquid holdup volume to permit reasonably rapid response time (10
      --> 90% rise time of approximately 1.2 min for a transient event at a liquid flow
      rate of 500 microL/min) while permitting quantitative removal of common soluble
      atmospheric trace gases at flow rates up to 1.7 L/min. The latter attribute
      permits the use of the device as the first element in a particle sampling and
      analysis system for the quantitative removal of potentially interfering soluble
      trace gases. Particle losses in the denuder range from 0.9 to 2.9% over an
      aerodynamic diameter range of 0.38-3.48 microm, averaging 1.8%. However, only
      approximately 0.5% of the particles actually appears in the denuder effluent
      liquid. The relatively compact (300 mm H x 57 mm W x 26 mm D) wet denuder should
      be attractive in a number of applications. We show excellent agreement for HONO
      measurements with a conventional larger parallel plate wetted denuder in field
      measurements.

PMID- 14961758
TI  - Laparoscopic gastrostomy and jejunostomy.
AB  - BACKGROUND: The percutaneous/endoscopic gastrostomy (PEG) has rapidly replaced
      the surgical gastrostomy as the preferred route for enteral access. In patients
      who are not candidates for a PEG, we prefer a laparoscopic gastrostomy to an open
      gastrostomy. Similarly, in patients who require a surgical jejunostomy, we prefer
      a laparoscopic approach. Minimally invasive techniques have several advantages
      over the standard open surgery. The purpose of this article is to review the
      indications, various techniques, and outcomes of laparoscopic gastrostomy and
      jejunostomy tubes. DATA SOURCES: Medline search from 1959-2002. CONCLUSIONS: The
      PEG remains the procedure of choice for placement of a gastrostomy. Laparoscopic
      gastrostomy is an excellent choice for patients who are not candidates for a PEG.
      Similarly, laparoscopic jejunostomy is an excellent choice for patients who
      require enteral access, but have contraindications to a gastrostomy tube.
      Placement of laparoscopic gastrostomy andjejunostomy tubes can be safely
      performed, and the success and complication rates of these procedures compare
      favorably with those of the corresponding open surgical procedure. Laparotomy is
      rarely needed to place enteral feeding tubes. Cost analysis has shown that
      laparoscopic procedures are similar to open procedures.

PMID- 14961759
TI  - Laparoscopic approach to pancreatic disease.
AB  - Minimally invasive techniques in the treatment of pancreatic disease have been
      revolutionary and provide clinical evidence of decreased morbidity and comparable
      efficacy to traditional, open surgery. Although the use of other laparoscopic
      solid organ procedures has outdistanced therapeutic laparoscopy of the pancreas,
      the advent of laparoscopic pancreatic surgery preceded the general use of
      laparoscopic cholecystectomy and the popularity of other solid organ procedures.
      This article describes four main applications of laparoscopic pancreatic
      procedures, which are staging of pancreatic cancer, palliative bypass procedures
      for pancreatic cancer, resection of benign and malignant pancreatic disease, and
      pancreatic drainage procedures.

PMID- 14961760
TI  - Current status of the laparoscopic approach to liver resection.
AB  - We present the current status of laparoscopic approach to liver resection.
      Indications, surgical techniques, complications, and results are based on a
      review of the literature. RESULTS: Over 700 laparoscopic liver procedures have
      been reported since 1991. A vast majority (70%) of the procedures were performed
      for benign lesions. The remaining 30% were malignant tumors. Cyst fenestration
      and unroofing was the most frequently performed laparoscopic liver procedure (245
      patients). Overall morbidity was 12% (56 patients). The overall conversion rate
      was 11% (36 patients). CONCLUSION: Laparoscopic liver resection is feasible, with
      acceptable morbidity and mortality. Results should be confirmed in further
      prospective studies, especially for resection of malignant tumors.

PMID- 14961761
TI  - Management of fixed deformities in total knee arthroplasty.
AB  - Total knee arthroplasty (TKA) has developed significantly since the early 1970s.
      The basic principles have not changed over the past 30 years; however, the
      techniques and prostheses have improved a great deal. The TKA must correct
      deformity while balancing the ligaments and equalizing the flexion and extension
      gaps. Deformity can be a result of bone angulation or ligament imbalance. Bone
      deformity must be isolated out to the diaphysis, metaphysis, or articular surface
      of the knee. The latter two areas can be managed at the same time as the
      arthroplasty. Diaphyseal changes that are greater than 20 degrees of angulation
      most often require a separate operative procedure. Ligament imbalance can be
      managed with either lengthening of the tightened ligament or tightening of the
      lax ligament. While lengthening is the easier of the two approaches, both
      techniques are acceptable when performed correctly. Deformity of the knee can be
      a challenging problem, but with proper planning, the results are very acceptable
      and rewarding both for the patient and the operating surgeon.

PMID- 14961762
TI  - Scientific basis for selection of emergency medical examination gloves for
      emergency medical technicians, paramedics, firefighters, and emergency department
      personnel.
AB  - Dusting powders were first applied to gloves to facilitate donning. After 1980,
      manufacturers devised innovative techniques to manufacture gloves without dusting
      powders. It has been well documented that the powders on gloves present a health
      hazard to patients, as well as healthcare workers. First, these powders elicit
      tissue toxicity in every tissue in the body. Second, these powders serve as
      carriers of latex allergen and may precipitate a life-threatening allergic
      reaction in sensitized patients. These well-documented hazards of glove powders
      have caused a growing number of emergency medical technicians, paramedics,
      firelighters, and hospitals to abandon the use of powdered emergency medical
      examination gloves, using only powder-free gloves. Powder-free latex as well as
      non-latex gloves are now available to emergency medical technicians, paramedics,
      firefighters, and emergency department personnel. The use of powder-free natural
      rubber latex-free gloves is especially important to emergency medical
      technicians, paramedics, firefighters, as well as emergency department personnel
      to avoid eliciting an allergic reaction in the latex sensitized patient. The
      majority of our emergency medical technicians, paramedics and firefighters are
      now wearing powder-free emergency medical examination gloves that comply with the
      stringent Codes and Standards established by the National Fire Protection
      Association (NFPA), while very few hospital emergency department personnel have
      been provided with NFPA approved gloves. It is the purpose of this report to
      review the stringent regulations for emergency medical examination gloves that
      are outlined by the NFPA. This design and performance Standard was devised by the
      NFPA to address protective clothing for emergency medical operations. The design
      and performance requirement of the emergency medical examination gloves were
      described in the NFPA 1999, Standard on Protective Clothing for Emergency Medical
      Operations, 1997 Edition. In September 2003, the emergency medical examination
      glove must meet the new design and performance requirements of emergency medical
      examination gloves discussed

PMID- 14961763
TI  - Ultraviolet eye radiation: the problem and solutions.
AB  - Ultraviolet radiation (UVR) can cause damage to the eyes. Some of the damage is
      acute, with immediate signs and symptoms, while some of the damage is the result
      of cumulative or long-term UVR exposure. Because the most common source of UVR is
      the sun, individuals who are exposed to sunny environments should be advised to
      protect themselves properly. Individuals should be counseled about proper eye
      protection from UVR in sunlight. It is important to know when eye protection is
      indicated. Protection involves wearing a wide-brimmed hat or cap and well
      designed sunglasses. The advisable sunglass features include the following: large
      eye size with side protection, less than 1% UV-B transmittance, less than 1% UV-A
      transmittance, gray or near-neutral colored lenses, good optical quality, and
      visible transmittance selected for visual comfort. Some clear spectacles or
      contact lenses also provide good levels of UV protection. When selecting
      sunglasses, it is always helpful to consult your eye care specialist.

PMID- 14961764
TI  - Nucling mediates apoptosis by inhibiting expression of galectin-3 through
      interference with nuclear factor kappaB signalling.
AB  - Nucling is a novel apoptosis-associated molecule, which is involved with
      cytochrome c /Apaf-1/caspase-9 apoptosome induction following pro-apoptotic
      stress. In the present study, we show first that Nucling is able to interact with
      galectin-3. Galectin-3 is known to participate in many biological processes,
      including apoptotic cell death. Nucling was found to down-regulate the expression
      level of galectin-3 mRNA/protein. Nucling-deficient cells, in which galectin-3
      expression is up-regulated, appeared to be resistant to some forms of pro
      apoptotic stress as compared with wild-type cells. In addition, the preputial
      gland from Nucling-deficient mice expressed a significant level of galectin-3 and
      exhibited a high incidence of inflammatory lesions, indicating that Nucling plays
      a crucial role in the homoeostasis of this gland by interacting with the galectin
      3 molecule and regulating the expression level of galectin-3. Up-regulation of
      galectin-3 was also observed in the heart, kidney, lung, testis and ovary of the
      Nucling-deficient mice. In order to confirm the functional interaction between
      Nucling and galectin-3, a well-documented candidate for the mediator of galectin
      3 expression, NF-kappaB (nuclear factor kappaB), was investigated as well.
      Nucling was shown to interfere with NF-kappaB activation via the nuclear
      translocation process of NF-kappaB/p65, thus inhibiting the expression of
      galectin-3. Taken together, we propose that Nucling mediates apoptosis by
      interacting and inhibiting expression of galectin-3.

PMID- 14961765
TI  - Quantification of mitochondrial sublimons in human fibrillating atria.
AB  - Supraventricular tachycardias, including AF (atrial fibrillation), and mtDNA
      (mitochondrial DNA) deletions may lead to dilated cardiomyopathy. It is unknown
      whether mtDNA function is impaired in the human atrium in AF. In the present
      study, we investigated the role of rearranged mtDNA 'sublimons' in the
      pathogenesis of AF. Right atrial biopsies were collected from 38 patients in AF
      and 35 patients with SR (sinus rhythm) undergoing elective cardiac surgery. Total
      DNA was extracted by standard methods. The break-point regions of the two most
      prevalent classes of sublimon were amplified by PCR using fluorescent
      oligonucleotides for the 3.75 kb partial duplication and the 2.83 kb deletion.
      Multiplex reactions included additional primers to amplify an internal genomic
      standard for semi-quantitative analysis. Reaction products were quantified as
      peak areas in the electrophoretogram and ratios computed of the sublimon
      abundance relative to the genomic standard. There was no difference in SCN
      (sublimon copy number) between AF and SR patients [19.09+/-28.29 compared with
      10.25+/-24.68, the difference was 0.28 (95% confidence interval, -0.04 and +0.61;
      P =0.08)]. SCN did not increase with age ( P =0.207) and was unrelated to AF
      duration ( P =0.661), left atrial diameter ( P =0.560), post-operative AF ( P
      =0.52), underlying disease ( P =0.94), medication and gender (2.84+/-0.72 in
      females vs 2.97+/-0.67 in males; P =0.431). In conclusion, our findings do not
      indicate any role of mtDNA in the pathophysiology of AF.

PMID- 14961766
TI  - Mapping of catalytically important residues in the rat L-histidine decarboxylase
      enzyme using bioinformatic and site-directed mutagenesis approaches.
AB  - HDC (L-histidine decarboxylase), the enzyme responsible for the catalytic
      production of histamine from L-histidine, belongs to an evolutionarily conserved
      family of vitamin B6-dependent enzymes known as the group II decarboxylases. Yet
      despite the obvious importance of histamine, mammalian HDC enzymes remain poorly
      characterized at both the biochemical and structural levels. By comparison with
      the recently described crystal structure of the homologous enzyme L-DOPA
      decarboxylase, we have been able to identify a number of conserved domains and
      motifs that are important also for HDC catalysis. This includes residues that
      were proposed to mediate events within the active site, and HDC proteins carrying
      mutations in these residues were inactive when expressed in reticulocyte cell
      lysates reactions. Our studies also suggest that a significant change in
      quartenary structure occurs during catalysis. This involves a protease sensitive
      loop, and incubating recombinant HDC with an L-histidine substrate analogue
      altered enzyme structure so that the loop was no longer exposed for tryptic
      proteolysis. In total, 27 mutant proteins were used to test the proposed
      importance of 34 different amino acid residues. This is the most extensive
      mutagenesis study yet to identify catalytically important residues in a mammalian
      HDC protein sequence and it provides a number of novel insights into the
      mechanism of histamine biosynthesis.

PMID- 14961769
TI  - Differences in enquiries to CancerBACUP information service by living
      arrangements.
AB  - The study's aim was to ascertain whether living alone is associated with the use
      of an independent cancer information service. An Enquirer Record Form is
      completed for every fifth enquirer to the service; two questions asking whether
      enquirers, patients, relatives/friends were living alone or with others where
      asked in association with the routine questions. A total of 552 callers were
      asked in a 5-week period, 77% of all callers in these categories. The main
      findings were: (1) the proportion of enquirers living alone was similar to the
      general population; (2) among enquirers, patients were more likely to live alone
      than relatives/friends; (3) requests differed by whether living alone and by type
      of enquirer, for example, significantly more people living with others requested
      emotional support than those living alone, and this contrast was most marked for
      patients than relatives/friends. This study, notwithstanding its limitations,
      highlights some of the differences in the use of a service and demonstrates the
      complexity of information and support seeking.

PMID- 14961770
TI  - Presentation and outcome of 93 cases of craniopharyngioma.
AB  - We studied a series of 93 patients diagnosed with craniopharyngioma during a 15
      year period with respect to presenting symptom, clinical course and management.
      The majority (62%) of patients were men, and had presented with neurological
      symptoms (75%), with headaches (82%) being the most common presenting symptom.
      The incidence of certain endocrine and ophthalmic symptoms varied little from
      that in the literature, on the other hand, the incidence of certain other
      symptoms did differ markedly from the literature. For example, loss of libido and
      amenorrhoea were seen at a much lower frequency than that stated in the
      literature. Hypertension, sensorimotor symptoms and urinary incontinence were not
      seen at all in our patients. In most cases diagnosis was made by a cranial CT
      scan, which is more sensitive than plain radiography for detection of enlarged
      sella turcica (69% vs. 24%; P < 0.001). In over 90% of cases, therapy consisted
      of removal of a variable portion of the tumour, with or without radiotherapy.
      Post-operative mortality was substantially reduced in cases treated by
      radiotherapy (P < 0.05). The most common post-operative complications in all
      cases were recurrence of disease, panhypopituitarism and diabetes insipidus.

PMID- 14961771
TI  - A qualitative evaluation of an adolescent cancer unit.
AB  - MULHALL A., KELLY D. & PEARCE S. (2004) European Journal of Cancer Care13, 16-22
      A qualitative evaluation of an adolescent cancer unit The Expert Advisory Group
      on Cancer (1995) recommended that cancer centres in the UK should make provision
      for adolescents with cancer. However, although their number is growing, only a
      small number of specialist adolescent cancer units currently exist, and teenagers
      may often be treated in more general settings. To date, no formal evaluation of
      adolescent cancer units has taken place. This study adopted a qualitative
      approach to evaluate the first specialist adolescent oncology unit, which was
      established in the UK 10 years ago. The aim was to provide insight into: the
      culture of the unit; the experiences of patients and parents on the unit and the
      staff who worked there; and how the unit was valued by these groups. Semi
      structured interviews were conducted with 10 teenagers with cancer, 10 parents
      and 14 professionals. Systematic non-participant observation of routine
      activities in the unit was undertaken also. Interview transcripts and
      observational data were analysed to identify key themes and categories. Six
      categories emerged from the data: (1) cancer and the cancer unit: although the
      word cancer had negative connotations, it provided a common supportive bond for
      adolescents and families on the unit; (2) what it feels like over time: key
      points in the adolescent cancer experience were emphasized as significant. These
      included diagnosis, end of treatment and recurrence of cancer; (3) physical
      structures and facilities: these were focused around the needs of adolescents
      with cancer and helped to provide a suitable environment of care; (4) the social
      context: approaches to care were relaxed in nature and suited the needs of
      adolescents and their families; (5) the family: there was an emphasis on
      maintaining normal routines whilst managing the impact of cancer on family
      relationships; and (6) specialism and expertise: the availability of an expert
      team of professionals with specialized insight into adolescents' needs was
      pivotal to creating an appropriate environment of care. In conclusion, the
      complex care and treatment needs of adolescents with cancer may best be met by
      specialist units.

PMID- 14961772
TI  - The psychological needs of patients receiving chemotherapy: an exploration of
      nurse perceptions.
AB  - This study explored the perceptions of a group of registered oncology nurses
      about the psychological needs of patients with cancer receiving chemotherapy and
      how the nurses meet these. Eight nurses who provided chemotherapy and were
      working in a local oncology centre participated. A semi-structured interview was
      used to explore nurses' perceptions, and how they meet these patients' needs. The
      analysis of interview transcripts revealed that these nurses agreed that patients
      with cancer receiving chemotherapy had psychological needs. Moreover, they were
      conscious that some of the physical side-effects could have a psychological
      impact on the patients. Although nurses did not use any assessment tool for
      psychological assessment, they identified two main stages during the treatment
      when patients needed more psychological support: at the beginning and at the end
      of the chemotherapy. They explained how they tried to meet patients'
      psychological needs but they also mentioned several factors that influenced the
      psychological support that patients received.

PMID- 14961773
TI  - A survey of breast cancer patients' views on entry into several clinical studies.
AB  - During the course of their treatment and follow-up, women with breast cancer are
      likely to be asked to join a number of different clinical studies. Some local
      research ethics committees have expressed concerns about entry of individual
      patients into multiple research studies. A survey was undertaken to improve
      understanding of patients' own perceptions of participation in several clinical
      studies. A total of 96 patients who had previously undergone surgery for breast
      cancer from January to June 2000 were sent a questionnaire 6-12 months after
      completion of primary treatment. Eighty four per cent of questionnaires were
      returned of which 62% were from patients who had been approached to enter at
      least one clinical study. Sixty-four per cent of patients believed that there
      should not be a limit on the number of clinical studies offered to patients.
      Furthermore, three quarters of all patients would have considered entering more
      than one study if adequate explanation and written information were provided.
      Most patients felt that their participation in a clinical study was worthwhile
      and no patients surveyed regretted their decision to take part in a study. Almost
      two-thirds of patients who returned questionnaires believed there should not be a
      maximum number of studies offered to them. This survey suggests that the majority
      of patients are prepared to participate in more than one clinical study when
      adequate information and explanation are provided.

PMID- 14961774
TI  - An investigation of inpatient referrals to a clinical psychologist in a hospice.
AB  - A clinical psychologist, in a new post in a hospice, developed an assessment,
      therapeutic and consultation role. A retrospective, diary-based audit was made of
      the inpatients referred during the first 2 years, allowing an examination of
      referral practices and changes over time as the psychologist's role developed.
      During the 2 years 11% of the hospice inpatients were referred, consistent with
      previous published work in this area. Referrals increased from 10% in year 1 to
      12% in year 2. Referrals were not skewed in terms of patient gender or diagnosis
      but younger patients were referred more. Comparison with other studies suggests
      the psychologist's gender may influence referral rates of woman patients.
      Referrals for depression and anxiety increased in year 2 but decreased for pain.
      The number of patients seen with marital/family stresses also increased with
      time. Such patients required the most psychological input. Patients with problems
      of alcohol misuse or dementia were particularly challenging for the hospice team
      and specific training was developed. The psychologist's role is discussed in the
      light of these findings, particularly in enhancing the multidisciplinary team's
      holistic approach to the patient and their family, by emphasizing the patient's
      experience and the collaborative basis of care.

PMID- 14961775
TI  - Occupational therapy intervention with patients with breast cancer: a survey.
AB  - Occupational therapists (OTs) working with patients with breast cancer provide a
      variety of therapeutic interventions. A survey was undertaken to record the
      different assessments and treatments employed by OTs in a specialist cancer
      centre with the type and length of interventions recorded on a log sheet by each
      therapist over a period of a month. A significant amount of time was spent
      facilitating educational programmes, teaching relaxation techniques and exploring
      strategies for managing breathlessness and fatigue. However, documentation and
      report writing consumed the largest proportion of the therapists' time. Less time
      was spent on assessment of activities of daily living and home assessments, often
      perceived to be the traditional domain of OTs.

PMID- 14961776
TI  - Communicating suffering in primary stage head and neck cancer.
AB  - The findings presented in this discussion seek to make a contribution to quality
      of life (QOL) research, by highlighting the import of factors affecting the
      communication of primary stage head and neck cancer patient's experiences of
      suffering after treatments by their clinicians. Qualitative research methodology
      based on open-ended interviews with 18 survivors of American Joint Committee on
      Cancer (AJCC) Stage I and Stage II, squamous cell carcinoma of the head and neck
      (SCCHN) were used. The interviews were transcribed verbatim and thematically
      analysed. In this preliminary analysis, three important themes emerged: (1) a
      self diminished by cancer; (2) the fear of addiction to pain medications; and (3)
      hopelessness and the loss of meaning in life after SCCHN. Our present findings
      indicate that SCCHN patients understand their experiences of cancer and under
      report their experiences of suffering mainly because of fear. These include fears
      of: being further diminished by SCCHN, fears of addiction, and an inability to
      cope with the additional losses associated with SCCHN. As a consequence, and
      perhaps, because of a failure the part of clinicians and patients to adequately
      address these fears, SCCHN patients may also experience greater psychological
      morbidity, becoming fatalistic about biomedicine's ability to restore them to
      health after cancer, or related symptoms, including pain, despite being 'cured.'
      This study provides a perspective on why this under-reporting occurs, thereby
      potentially enhancing clinician-patient communication and the QOL of SCCHN
      patients who present with curable disease.

PMID- 14961777
TI  - Measuring information strategies in oncology - developing an information
      satisfaction questionnaire.
AB  - The benefits of providing accurate and culturally sensitive information for
      patients are now undisputable and information strategies are generally being
      adopted nationally. Measuring their benefits and adapting strategies to local
      needs is now a new challenge. Although questionnaires to measure global
      satisfaction are available, no concise tool has previously existed to
      specifically measure the information aspects of care. The aims of this study are:
      to establish which aspects of information were most important to the patients
      during their cancer pathway; to develop a robust single-page questionnaire that
      is sensitive to patient priorities to measure and compare satisfaction between
      patient groups; and to audit information provision within routine clinical
      practice. Seventy-seven consecutive patients were asked to complete a priority
      list of which aspects of information were most important to them during their
      recent cancer care. A total of 303 answers were categorized into five final
      categories of equal weighting. The data were combined with demographic issues to
      produce a robust one-page questionnaire which has been adopted formally by the
      West Anglia Cancer Network. One hundred consecutive patients were then audited to
      highlight the information shortcomings of a busy community oncology department
      and the findings are reforming information services. We recommend the use of this
      practical audit tool in routine clinical practice, which can be downloaded free
      from cancernet.co.uk in seven languages.

PMID- 14961778
TI  - Chemotherapy-related nausea and vomiting - past reflections, present practice and
      future management.
AB  - Although much progress has occurred in the last decade regarding the management
      of chemotherapy-induced nausea and vomiting, these remain among the most
      intolerable side-effects of treatment and patients continue to report the
      negative impact such symptoms have on their ability to enjoy life. Inadequate
      control of nausea and vomiting reduces patients' quality of life and functional
      status and jeopardizes the delivery of optimal treatment, so making its
      management a priority for oncology health care workers. This article will reflect
      on past and present evidence regarding the management of chemotherapy-induced
      nausea and vomiting while highlighting some of the most recent scientific
      advances before drawing conclusions about the future management of this
      troublesome symptom for patients receiving chemotherapy.

PMID- 14961779
TI  - Implementing the 2-week wait rule for cancer referral in the UK: general
      practitioners' views and practices.
AB  - The 2-week wait rule for cancer referrals became effective in December 2000 for
      all cancers treated by the National Health Service in the UK. Attainment of this
      target depends initially on appropriate and timely referral by general
      practitioners (GPs). General practitioners' views and referral practices under
      the 2-week wait rule were examined based on a postal survey of 508 GPs in an
      inner London area (65% response). Data on mode of referral indicated that 90% of
      GPs used the urgent suspected cancer form, although 38% also sent a letter with
      further information. General practitioners generally regarded the 2-week wait
      rule as working well in terms of improving patients' initial access, and 50%
      thought communication with the hospital had improved. However, 46% expressed some
      concerns, including problems arising from the different sets of forms required by
      local cancer networks, the lack of a dedicated referral form for breast cancer,
      and feelings of a loss of autonomy. General practitioners also acknowledged an
      element of over-referral under this rule due to the effects of clinical
      uncertainty and patient pressure and their concerns about increased waiting times
      for non-target referrals. The survey therefore indicates that GPs are generally
      positive about the 2-week wait rule but identified some problems of
      implementation including a need for standardized national cancer referral forms.

PMID- 14961780
TI  - Young adults with cancer: parents' interactions with health care professionals.
AB  - This paper examines the relationship between medical professionals and parents of
      young adults who are being treated by them for cancer. This study aims to
      discover what practices and procedures make the cancer journey easier or more
      difficult to manage for parents in the medical setting. Many studies of carers
      focus on spouses, little attention has been paid to parents of young adults in
      this context. Self-selected parents responded to an appeal for narratives about
      their adult son or daughter's cancer experience. A narrative correspondence
      method was used relying on contributions of a qualitative nature submitted in
      written form and analysed through the identification of emerging themes.
      Interactions with health professionals have a far-reaching effect on parents'
      experience. A clear understanding needs to be established at an early stage with
      agreement by all parties on how information and decision making should be shared.
      If parents feel excluded or uninformed about procedures, or believe that their
      son or daughter is receiving less than optimum care, this results in feelings of
      helplessness and frustration. While many of the issues identified in this paper
      might apply to relatives of cancer patients in other age groups, the effect of
      life stage during young adulthood exacerbates the complexities of the medical
      setting.

PMID- 14961787
TI  - Left ventricular long-axis function is reduced in patients with rheumatic mitral
      stenosis.
AB  - Left ventricular long-axis function evaluated by M-mode or tissue Doppler
      echocardiography has been shown to be useful indexes of left ventricular systolic
      function; however it has not been evaluated in patients with mitral stenosis. We
      examined the left ventricular long-axis function of the patients with pure mitral
      stenosis and normal global systolic function as assessed by fractional shortening
      of the left ventricle (LV). Fifty-two patients with pure mitral stenosis and
      twenty-two healthy controls were evaluated by echocardiography. Although there
      was no statistically significant difference in global systolic function, M-mode
      derived systolic motion of the septal side and (12 +/- 3 vs 14.4 +/- 1.5 mm, P =
      0.016) the lateral side of mitral annulus (13.2 +/- 3 vs 16.8 +/- 2 mm, P =
      0.001) were both significantly lower in the patients with mitral stenosis than
      control subjects. Similarly tissue Doppler systolic velocity of the septal
      annulus (7.6 +/- 1.1 vs 10.4 +/- 3.2 cm/s, P = 0.03) and lateral mitral annulus
      (7.6 +/- 1.1 vs 10.4 +/- 3.2 cm/s, P = 0.003) were also significantly lower in
      patients with mitral stenosis than in controls. There was a statistically
      significant correlation between septal annular motion and annular velocity (r =
      0.643, P = 0.002). Septal annular motion and annular velocity were also
      correlated with left atrial ejection fraction (r = 0.338, P = 0.005 and r =
      0.676, P = 0.001, respectively). Thus, patients with mitral stenosis had
      significantly impaired long-axis function evaluated by M-mode or tissue Doppler
      echocardiography despite normal global systolic function.

PMID- 14961788
TI  - Role of dobutamine-atropine stress echocardiography in prognostic evaluation of
      300 women.
AB  - BACKGROUND: Dobutamine-atropine stress echocardiography (DASE) is a safe and
      accurate method to diagnose coronary artery disease (CAD), and can identify
      individuals at high risk for cardiac events such as myocardial infarction and
      cardiac-related death. The literature is limited regarding the prognostic value
      of DASE in women. OBJECTIVE: The objective was to determine the prognostic value
      of DASE in 300 women with known or suspected CAD. RESULTS: The 300 women
      underwent DASE and were followed up for 65 months (mean: 27 months). Ninety-five
      women had positive tests and 205 had negative tests. We demonstrated that women
      with negative tests had a 94% hard-event-free survival rate at follow-up
      (myocardial infarction and death), and in those with positive tests the event
      free survival rate was 27% (P = 0.0003). The difference between women with
      positive and negative tests was also significant when minor events and total
      events were considered. Women with positive tests had 16.7 times more chance of
      having events than women with negative tests. Furthermore, women with positive
      tests but without cardiac events at follow-up (mean of peak WMSI - rest WMSI =
      0.24 +/- 0.16) had less ischemic myocardium than women with positive tests and
      cardiac events at follow-up (mean of peak WMSI - rest WMSI = 0.34 +/- 0.26)(P <
      0.04). CONCLUSION: Dobutamine-atropine stress echocardiography has good
      prognostic value for cardiac events in women. Women with negative tests have low
      probability for follow-up infarction or death. Women with positive tests and
      higher severity of induced ischemia have the highest incidence of cardiac events.

PMID- 14961789
TI  - Quantitative intravenous myocardial contrast echocardiography predicts recovery
      of left ventricular function after revascularization in chronic coronary artery
      disease.
AB  - BACKGROUND: Quantitative intravenous myocardial contrast echocardiography (MCE)
      has been shown to measure regional myocardial blood flow velocity noninvasively.
      PURPOSE: To determine whether quantitative intravenous MCE could be used
      clinically to predict functional recovery after revascularization in patients
      with chronic coronary artery disease. METHODS: Twenty-eight patients with chronic
      stable coronary artery disease and resting regional left ventricular dysfunction
      were included in this study. The study permits myocardial perfusion analysis by
      intravenous MCE before revascularization with continuous infusion of Levovist and
      intermittent ultrasonic exposure. Wall motion assessment by echocardiography at
      rest was repeated after long-term follow-up period (7 +/- 2 months). In
      dysfunctional segments, we analyzed myocardial perfusion quantitatively by
      fitting to an exponential function, Y = A(1 - e-betat) to obtain the rate of rise
      (beta) of background-subtracted intensity, which represented myocardial blood
      flow velocity. RESULTS: Of the 101 revascularized dysfunctional segments, MCE was
      adequately visualized in 91 (90%) segments, and wall motion was recovered in 45
      (49%) segments. The value of beta in the recovery segments was significantly
      higher than that in nonrecovery segments (0.80 +/- 0.50 vs 0.39 +/- 0.24, P <
      0.001). The value of beta > 0.5 predicted recovery of segmental function with a
      sensitivity of 71%, specificity of 78%. CONCLUSION: Quantitative intravenous MCE
      can predict functional recovery after revascularization in patients with chronic
      coronary artery disease.

PMID- 14961790
TI  - The effect of time and of vasoactive drugs on capillary leakage induced during
      myocardial contrast echocardiography.
AB  - BACKGROUND: Premature ventricular contractions (PVC), capillary leakage, and
      petechial hemorrhage can occur during myocardial contrast echocardiography (MCE).
      The effects occur as a result of the interaction of contrast agent microbubbles
      and the ultrasound, but the detailed etiology of the effects is not yet clear.
      This study tested the hypothesis that the capillary leakage results from a
      physiological response to injury, which might be protracted and modulated by
      vasoactive drugs. METHODS: Hairless rats were anesthetized and transthoracically
      scanned with a diagnostic ultrasound system (GE Vingmed System V) at 1.7 MHz with
      1:4 triggered frames at end systole. The scan head and rats were mounted in a 37
      degrees C water bath to assure free-field conditions and placement of the heart
      at a similar focal distance as humans. A tail vein was cannulated for injections
      of Optison contrast agent, vasoactive medications, and Evans Blue dye (EB). EB
      was injected as a marker of capillary leakage before or after scanning. RESULTS:
      PVCs, petechia, and capillary leakage occurred during ultrasound exposure of
      microbubbles in myocardium, with no effects detected in shams. The influence of
      the vasoactive medications propranolol and isoproterenol on the effects did not
      support the hypothesis. Capillary leakage occurred during and postexposure, but
      diminished for EB injection 20 minutes after scanning with or without
      isoproterenol pretreatment. CONCLUSION: MCE induced PVCs, petechia, and capillary
      leakage, all of which ended immediately or within 20 minutes after the
      examination. Contrary to the hypothesis of a physiological mechanism, the
      capillary leakage appears to be primarily a mechanical effect rather than a
      physiological response.

PMID- 14961791
TI  - Value of tissue Doppler imaging to predict left ventricular filling pressure in
      patients with coronary artery disease.
AB  - Assessment of left ventricular (LV) diastolic filling pressure provides important
      information on the hemodynamic status in the general population. The aim of our
      study was to investigate the reliability of tissue Doppler imaging (TDI) in
      estimating left ventricular filling pressure in patients with coronary artery
      disease (CAD). We prospectively studied 32 consecutive CAD-patients, mean age 64
      +/- 12 years, in sinus rhythm. All patients underwent cardiac catheterization and
      echocardiography within the same hour. Catheterization investigated pre-A-wave
      pressure (preA) and LV ejection fraction (LVEF). Echocardiographic LVEF was
      calculated using wall motion indexes (WMI) with segmental division of LV wall.
      The following Doppler parameters were assessed: (1) PW Doppler signals from the
      mitral inflow (E), (2) PW TDI of the mitral annulus (E'), thus allowing to obtain
      the mitral inflow to annulus ratio (E/E'). The best correlation between invasive
      and echocardiographic LVEF was observed using WMI (r = 0.91). The correlations
      between preA and E, E', and E/E' were significant (r = 0.36, r = 0.38, and r =
      0.60, respectively). In patients with LVEF >50%, no correlation between E/E' and
      preA was found (r = 0.18, P = 0.44), whereas with LVEF <50%, this correlation was
      strong (r = 0.76, P < 0.001). In patients with myocardial infarction, the
      correlation between E/E' and preA was significant whatever the localization of
      myocardial infarction (r > 0.71, P < 0.05). ROC curve analysis identified an
      E/E'>9 to be the best cut-off value related to preA > 15 mmHg. We conclude that
      the mitral inflow-to-annulus ratio is a reliable method in CAD patients and
      allows determination of LV filling pressure when LVEF <50%.

PMID- 14961792
TI  - Remodeling of coronary arteries in diabetic patients-an intravascular ultrasound
      study.
AB  - BACKGROUND: Coronary artery remodeling is a structural change in the vessel wall
      and typically in response to atherosclerotic plaque. The nature of coronary
      remodeling has been described in different clinical situations. However,
      remodeling characteristics of coronary arteries of diabetic patients have never
      been studied. HYPOTHESIS: We tested the hypothesis that positive remodeling of
      coronary artery in response to atherosclerotic plaque in diabetic patients would
      be less compared to nondiabetic patients. METHODS: Coronary intravascular
      ultrasound analysis of data in 26 consecutive patients (12 diabetic and 14
      nondiabetic) was performed. Linear regression analyses of vessel area versus
      plaque area were carried out to establish a relation between the degree of plaque
      and the extent of remodeling in diabetic and nondiabetic groups. RESULTS: The
      positive remodeling quantified as the slope of the regression line was similar in
      both the groups (diabetic group 1.32 and nondiabetic group 0.80) when all
      segments with different plaque areas were considered (P > 0.05). However, the
      diabetic group had greater positive remodeling in segments with plaque area less
      than 55%, as the slope for diabetic group was 2.01 and nondiabetic group was 1.40
      (P < 0.05). CONCLUSIONS: Both the diabetic and nondiabetic patients had positive
      remodeling in response to atherosclerotic plaque formation. Diabetics had greater
      positive remodeling in the early stages of atherosclerosis compared to
      nondiabetics, thus providing evidence against our hypothesis. The adverse
      clinical outcomes in diabetics may not be due to inadequate positive remodeling
      of coronary arteries as previously thought.

PMID- 14961793
TI  - Unusually large left atrial myxoma presenting with severe mitral valve
      obstruction symptoms.
AB  - A 13-year-old girl with the complaint of severe mitral valve obstruction symptoms
      was diagnosed as having an unusually large left atrial tumor by echocardiography.
      The giant mass was surgically removed and the postoperative course was
      uneventful. Histologic examination confirmed the mass was a benign atrial myxoma.

PMID- 14961794
TI  - The use of contrast echocardiography in the diagnosis of an unusual cause of
      congestive heart failure: achalasia.
AB  - Extrinsic compression of the left atrium is a potentially life-threatening but
      unusual cause of congestive heart failure. Achalasia is a motility disorder
      characterized by impaired relaxation of the lower esophageal sphincter and
      dilation of the distal two-thirds of the esophagus. We report only the third
      known case in the world literature of massive left atrial compression by a
      dilated esophagus in a patient with achalasia. The use of contrast
      echocardiography with perflutren protein-type A microspheres allowed for
      differentiation between a compressive vascular structure and the esophagus. This
      resulted in prompt treatment leading to hemodynamic stability after nasogastric
      decompression and Botulinum toxin injection at the gastroesophageal junction.

PMID- 14961795
TI  - Spontaneous coronary artery dissection with pseudoaneurysm formation diagnosed by
      intravascular ultrasound: a case report.
AB  - Spontaneous coronary artery dissection is a rare cause of myocardial ischemia.
      Coronary artery pseudoaneurysm may occur after percutaneous coronary
      interventions and rarely spontaneously. We present a patient who had spontaneous
      coronary artery dissection with formation of a pseudoaneurysm diagnosed by
      intravascular ultrasound.

PMID- 14961796
TI  - Three-dimensional echocardiography of intracardiac masses.
AB  - We describe two cases in which three-dimensional echocardiography provided unique
      anatomical data. This information enhanced the diagnostic power of two
      dimensional echocardiography by improving confidence in interpretation and by
      providing distinctive spatial insights.

PMID- 14961797
TI  - Usefulness of transthoracic echocardiography to detect coronary aneurysm in young
      adult: two cases of acute myocardial infarction due to Kawasaki disease.
AB  - Transthoracic echocardiography is useful for evaluation of the coronary arteries
      in infants and children with Kawasaki disease. In adults, however, transthoracic
      echocardiography often cannot detect or accurately estimate coronary artery
      lesions. We describe two young adults admitted for a diagnosis of acute
      myocardial infarction ascribed to Kawasaki disease and treated by angioplasty.
      Coronary aneurysms were not evident in either patient at the time of angioplasty.
      However, follow-up transthoracic echocardiography revealed coronary aneurysms at
      the culprit lesions. On follow-up angiograms, we identified a new coronary
      aneurysm in the first patient, and a regressed coronary aneurysm in the second,
      confirmed by intravascular ultrasound imaging. These cases suggest that
      transthoracic echocardiography plays an important role in the diagnosis and
      treatment of young adults with acute myocardial infarction due to Kawasaki
      disease.

PMID- 14961798
TI  - Double-chambered right ventricle associated with mural and pulmonic valve
      endocarditis: description of a clinical case and review of the literature.
AB  - A double-chambered right ventricle is a relatively uncommon congenital cardiac
      defect characterized by the presence of anomalous muscle bundles dividing the
      right ventricle into a high-pressure proximal chamber and a low-pressure distal
      chamber. This pathology is often wrongly diagnosed in adult patients. We report
      the first case of a patient with double-chambered right ventricle associated with
      a mural and pulmonic valve endocarditis caused by Streptococcus parasanguis
      diagnosed with two-dimensional echocardiography. During the course of treatment,
      the patient suffered from a septic pulmonary embolism, and subsequently required
      surgical intervention, which confirmed the echocardiographic findings.

PMID- 14961799
TI  - Spontaneous coronary artery dissection, aneurysms, and pseudoaneurysms: a review.
AB  - Spontaneous coronary artery dissection is a rare cause of myocardial ischemia and
      sudden death. Coronary aneurysms and pseudoaneurysms, which may occur after
      percutaneous coronary interventions, rarely occur spontaneously. We review the
      pertinent medical literature and describe the intravascular findings of
      spontaneous coronary artery dissection, aneurysms, and pseudoaneurysms.

PMID- 14961800
TI  - Giant vegetation of the mitral valve simulating primary cardiac tumor.
AB  - A case of a giant vegetation of the mitral valve causing sudden death of the
      patient is reported. The case underlines that urgent removal of a big mass must
      always be considered because of the risk of sudden death or catastrophic
      embolism. Echocardiographic differential diagnosis of a mass is discussed and is
      crucial for the choice of the strategy.

PMID- 14961801
TI  - Transesophageal echocardiographic demonstration of biatrial myxoma.

PMID- 14961802
TI  - Extension of bronchogenic carcinoma through pulmonary vein into the left atrium
      detected by echocardiography.
AB  - This is the case of a 46-year-old female recently diagnosed with a squamous cell
      bronchogenic carcinoma that spread through the pulmonary veins into the left
      atrium. This mass was initially seen on surface echocardiography as emanating
      from the pulmonary vein and subsequently confirmed to be arising from the right
      superior pulmonary vein by transesophageal echocardiography.

PMID- 14961803
TI  - Spontaneous echocardiographic contrast in the ascending aorta mimicking the
      appearance of aortic dissection in a patient with a left ventricular assist
      device.
AB  - We describe a patient with a previously implanted Jarvik 2000 left ventricular
      assist device (LVAD), who presented with bacteraemia and with features suspected
      for aortic dissection at the CT scan. However, transesophageal echocardiography
      showed competition in the ascending aorta between the retrograde pump flow and
      the anterograde transaortic output, which mimicked true aortic dissection and
      could be resolved by lowering the pump speed. As patients with LVAD are
      increasing in number, clinicians should be aware of this possible effect.

PMID- 14961804
TI  - The Doppler equation.

PMID- 14961805
TI  - Multiple fistulae connecting the right coronary artery to the coronary sinus.
AB  - Right coronary artery to coronary sinus fistula is a rare anomaly. We present a
      unique case of an adult patient with multiple fistulae from the right coronary
      artery draining into the coronary sinus near the posterior left atrium-left
      ventricle junction, first suspected by transthoracic two-dimensional
      echocardiography. The multiple openings were not seen by any invasive or
      noninvasive techniques and were noted only at the time of surgery. To our
      knowledge, this is the first case of multiple fistulae connecting the right
      coronary artery to the coronary sinus that has been reported in the English
      literature.

PMID- 14961834
TI  - Caries prevalence, oral health behavior, and attitudes in children residing in
      radiation-contaminated and -noncontaminated towns in Ukraine.
AB  - INTRODUCTION: Several studies investigating the oral health status of children
      living in Ukraine after the Chernobyl catastrophe revealed an increase of caries
      in children residing in radionucleotide-contaminated areas. PURPOSE: (1) To
      compare prevalence of dental caries in contaminated and noncontaminated towns;
      and (2) to determine if there is a difference between dental behaviors and
      attitudes of children residing in contaminated and noncontaminated areas that may
      have contributed to differences in caries prevalence. METHODS: Children aged 13
      14 were randomly selected in two towns of approximately the same population size
      (33 000): Ovruch (n = 119) from a contaminated area and Mirgorod (n = 100) from a
      noncontaminated area. Data on behaviors and attitudes were collected via a self
      administered questionnaire having six domains: (i) family background; (ii) dental
      anxiety; (iii) dental utilization; (iv) oral hygiene; (v) use of fluoride
      toothpaste; and (vi) sugar consumption. Oral examinations included information on
      carious lesions, restorations, missing teeth, and soft tissue abnormalities.
      Caries prevalence was compared using a t-test. Regression analysis was conducted
      to determine the independent contribution of oral hygiene behaviors and dental
      utilization. RESULTS: There was a significant difference in caries prevalence in
      the contaminated town (mean DMFT = 9.1 +/- 3.5) versus the noncontaminated town
      (mean DMFT = 5.7 +/- 1.4; P < 0.000). Oral hygiene practices, age, and
      utilization of dental services were not found to be associated with differences
      in DMFT score between the two communities. CONCLUSION: There was a significantly
      higher caries prevalence in a radiation-contaminated town compared to a
      noncontaminated town of Ukraine. The difference was not explained by differences
      in oral health knowledge, attitudes or behaviors.

PMID- 14961835
TI  - Assessing the responsiveness of measures of oral health-related quality of life.
AB  - OBJECTIVES: This paper illustrates ways of assessing the responsiveness of
      measures of oral health-related quality of life (OHRQoL) by examining the
      sensitivity of the oral health impact profile (OHIP)-14 to change when used to
      evaluate a dental care program for the elderly. METHODS: One hundred and sixteen
      elderly patients attending four municipally funded dental clinics completed a
      copy of the OHIP-14 prior to treatment and 1 month after the completion of
      treatment. The post-treatment questionnaire also included a global transition
      judgement that assessed subjects' perceptions of change in their oral health
      following treatment at the clinics. Change scores were calculated by subtracting
      post-treatment OHIP-14 scores from pre-treatment scores. The longitudinal
      construct validity of these change scores were assessed by means of their
      association with the global transition judgements. Measures of responsiveness
      included effect sizes for the change scores, the minimal important difference,
      and Guyatt's responsiveness index. An receiver operating characteristic (ROC)
      curve was constructed to determine the accuracy of the change scores in
      predicting whether patients had improved or not as a result of the treatment.
      RESULTS: Based on the global transition judgements, 60.2% of subjects reported
      improved oral health, 33.6% reported no change, and only 6.2% reported that it
      was a little worse. These changes are reflected in mean pre- and post-treatment
      OHIP-14 scores that declined from 15.8 to 11.5 (P < 0.001). Mean change scores
      showed a consistent gradient in the expected direction across categories of the
      global transition judgement, but differences between the groups were not
      significant. However, paired t-tests showed no significant differences in the pre
      and post-treatment scores of stable subjects, but showed significant declines
      for subjects who reported improvement. Analysis of data from stable subjects
      indicated that OHIP-14 had excellent test-retest reliability with an intraclass
      correlation coefficient (ICC) of 0.84. Effect size based on change scores for all
      subjects and subgroups of subjects were small to moderate. The ROC analysis
      indicated that OHIP-14 change scores were not good "diagnostic tests" of
      improvement. The minimal important difference for the OHIP-14 was of 5-scale
      points, but detecting this difference would require relatively large sample
      sizes. CONCLUSIONS: OHIP-14 appeared to be responsive to change. However, the
      magnitude of change that it detected in the context described here was modest,
      probably because it was designed primarily as a discriminative measure. The
      psychometric properties of the global transition judgements that often provide
      the "gold standard" for responsiveness studies need to be established.

PMID- 14961836
TI  - Why are we "weighting"? An assessment of a self-weighting approach to measuring
      oral health-related quality of life.
AB  - OBJECTIVE: To determine whether or not self-weighting at an item level
      contributes to the performance of an oral health-related quality-of-life measure.
      DESIGN: Data were collected in two national surveys conducted a month apart, one
      using the "weighted" measure and the other an "unweighted" version of the UK oral
      health-related quality-of-life measure. In addition, sociodemographic and self
      reported oral health status were recorded. RESULTS: The UK oral health-related
      quality-of-life measure discriminated between groups based on age group (<65, 65
      and older) and social class (higher and lower) irrespective of the version of the
      questionnaire used. Both versions also showed significant associations with self
      reported oral health: denture status (P < 0.01) and number of teeth possessed (P
      < 0.01). In addition, both versions demonstrated predictive ability in
      identifying those in prosthetic need (<20 teeth and without recourse to a
      denture, P < 0.01). CONCLUSION: Weighting the UK oral health-related quality-of
      life instrument does not improve the psychometric properties of the instrument
      and thus raises questions about the value of self-weighting at an item level.

PMID- 14961837
TI  - Reliability and validity of the Dental Satisfaction Questionnaire in a population
      of 23-year-olds in Norway.
AB  - OBJECTIVE: The aim of this study was to explore the internal structure,
      reliability, and construct validity of the Dental Satisfaction Questionnaire
      (DSQ) in a population of young adults in Norway. METHODS: The DSQ scale was
      mailed to a representative sample of 968 subjects aged 23 years in two Norwegian
      counties. The reliability assessment of the instrument was based on internal
      consistency analysis (Cronbach's alpha). A factor analysis (principal component)
      was used to confirm the internal structure of the scale. The construct validity
      of the DSQ was indicated by: (i) its correlation with the patients' beliefs
      regarding the way dentists deliver care, indexed by the Dental Beliefs Survey
      (DBS); and (ii) differences in DSQ scores between subjects who had dropped out
      from dental care at the age of 23 years and regular attenders. RESULTS: The
      response rate was 69%. The alpha (Cronbach's) coefficient for the overall
      construct of DSQ was 0.81 (n = 655), and 0.65 or more for the subscales pain
      management, quality, and access. The correlation coefficient between the sum
      scores of DSQ and DBS for the entire sample was r = -0.69. Subjects in the
      dropout group had significantly lower satisfaction with dental care than the rest
      of the group (P < 0.001). CONCLUSIONS: This study generally confirms the
      structure of the DSQ instrument and indicates that it is a reliable and valid
      instrument in cultures other than the one for which it was previously tested.

PMID- 14961838
TI  - Productive efficiency and its determinants in the Finnish Public Dental Service.
AB  - OBJECTIVE: Our objective was to investigate the cost efficiency of the Public
      Dental Service (PDS), which, until 2000, was responsible for organising dental
      care for children and younger adults born in 1956 and later. METHODS: Input and
      output data and information on various organisational and environmental
      characteristics were collected from 228 municipal PDS units in Finland. First,
      non-parametric data envelopment analysis (DEA) was employed to assess efficiency.
      In the second stage, econometric Tobit analysis was used to explore various
      predictors of cost efficiency, technical efficiency and allocative efficiency. As
      input in the DEA model we used personnel full-time equivalents and material and
      other costs expressed in monetary terms, and as output we used the number of
      treated patients. RESULTS: The study showed big differences in cost efficiency
      between the PDS units studied. The average cost inefficiency was 30%.
      Approximately two-thirds of the observed cost inefficiency was because of
      technical inefficiency and one-third because of allocative inefficiency. High
      state-subsidy levels, and a high proportion of young patients predicted
      inefficiency, and young population and low socioeconomic conditions in the
      municipality predicted efficiency. The results also indicated that many PDS units
      could have improved allocative efficiency by increasing the relative numbers of
      auxiliaries in relation to dentists. On the other hand, some units were too small
      to employ full-time dental hygienists efficiently. CONCLUSIONS: In the Finnish
      PDS, there are uncommitted resources that could be reallocated so as to improve
      overall efficiency.

PMID- 14961839
TI  - Measuring inequalities in the distribution of dental caries.
AB  - OBJECTIVES: To evaluate different measurements of prevalence and inequality in
      the distribution of dental caries as to their partial collinearity, and ability
      in expressing associations with the supply of fluoridated tap water, indices of
      socioeconomic status and provision of dental services. METHODS: The DMFT, the
      Significant Caries (SiC) Index, the proportions of children with high- (DMFT > or
      = 4) and rampant- (DMFT > or = 7) caries experience, caries-free children (DMFT =
      0), the Gini coefficient and the Dental Health Inequality Index (DHII) were the
      dental outcomes appraised in a sample comprising 18 718 oral examination records
      for 11- and 12-year-old schoolchildren in 131 towns of the state of Sao Paulo,
      Brazil. Spatial data analysis assessed the association between aggregate figures
      of dental indices and several covariates. RESULTS: The DMFT, the SiC Index and
      the proportions of children with high- and rampant-caries experience presented
      strong linear associations (Pearson r near or higher than 0.95), and an analogous
      profile of correlation with indicators of socioeconomic status, dental services
      and access to fluoride tap water. The same was observed for the DHII, the Gini
      coefficient and the proportion of caries-free children. These observations
      involve the perception of variables in each set as interchangeable tools for
      ecological studies assessing factors influencing, respectively, prevalence levels
      and inequality in the distribution of dental disease. CONCLUSION: An improved
      characterization of the skewed distribution of caries experience demands the
      concurrent estimation of figures of prevalence and inequality in dental outcomes.
      This strategy may contribute to the design of socially appropriate programmes of
      oral health promotion.

PMID- 14961840
TI  - An assessment of the validity and reliability of dental self-report items used in
      a National Child Nutrition Survey.
AB  - OBJECTIVES: To examine the clinical validity and reliability of dental self
      report items used in a National Child Nutrition Survey. METHODS: The study
      involved completion of dental self-report questionnaires by 6-9-year-old children
      who attended one of the three schools with ethnic distributions, similar to
      schools in the national survey, and their care-givers. Children were then
      dentally examined. RESULTS: Two hundred and four children (response rate 74.2%)
      returned questionnaires and were dentally examined. The highest degree of child
      and care-giver concordance for the self-reported dental items was for the "has
      had an extraction due to dental caries" item (kappa = 0.92), while the lowest was
      for the "brushes twice or more per day" item (kappa = 0.61). The prevalence of
      dental caries in the deciduous dentition was 67.6%. The mean dfs, mean DFS and
      mean number of missing primary teeth because of caries were 6.15 (SD 6.51), 0.83
      (SD 1.28) and 0.30 (SD 0.82), respectively. Caries severity was higher in
      children who reported brushing infrequently, having received a filling, having
      had an extraction because of caries, having been kept awake at night because of
      dental pain or having had a general anaesthetic for dental treatment. Values for
      self-report and clinical reliability were above 0.80 in all instances.
      CONCLUSIONS: The dental self-report items showed a high level of concordance
      between child and care-giver, and appeared to be clinically valid. The findings
      suggest that using dental self-report measures for children may be valuable in
      dental epidemiological investigations.

PMID- 14961841
TI  - Utilities of dentin regeneration among insured and uninsured adults.
AB  - OBJECTIVES: This population-based study measured utilities (preferences measured
      under conditions of uncertainty) of dentin regeneration (DR), a potential new
      therapy, root canal therapy (RCT), and extraction (EXT). METHODS: A
      representative sample of dentate adults (aged 18-69 years) was randomly selected
      from the Detroit area. A computer program was used to administer the standard
      gamble (SG) method and record utility score (US) for treatment options of a tooth
      with reversible pulpitis using the SG method. For the SG method, two anchor
      states were used: filled tooth with full oral health and filled tooth with severe
      and continuous pain leading to EXT. Additional data were obtained using a self
      administered questionnaire. RESULTS: Out of the 807 adults who resided in 446
      screened and selected households, a final sample of 630 adults who resided in 368
      households were interviewed. The mean US for DR with 75 and 95% success rates
      were 72.5 and 86.2 (on a 0-100 scale), respectively. The US for RCT and immediate
      EXT were 75.6 and 31.3, respectively. Eleven per cent of the adults valued DR
      with 95% success probability higher than a simple filling with full oral health
      for life. There were no statistically significant differences in the average US
      of DR between insured and uninsured adults. Factors such as gender, race,
      education, income and insurance status, experiences with EXTs or root canal
      treatment, regularity of dental visits, quality of life, and quality of oral
      health were not significantly associated with the scores of DR. There was,
      however, a small but significant interaction between race and dental insurance,
      and race and gender. CONCLUSION: This population-based study found that DR was
      highly preferred to other standard treatment options.

PMID- 14961842
TI  - The association between dental anxiety and oral health-related quality of life in
      Britain.
AB  - OBJECTIVE: The aim of this study was to identify associations between level of
      dental anxiety and the impact of oral health on quality of life (OHQOL) in
      Britain, controlling for sociodemographic and oral health status (self-reported)
      factors. METHODS: The basic research design included a cross-sectional study
      involving a random probability sample of 3000 UK residents. The outcome measures
      were: levels of dental anxiety, which were measured on the Corah Dental Anxiety
      Scale (DAS), and the impact of OHQOL, which was assessed using UK oral health
      related quality of life instrument (OHQoL-UK (W)). RESULTS: DAS was correlated
      with OHQoL-UK (W) scores (P < 0.01). Having controlled for sociodemographic
      factors (age, gender and social class) and oral health status factors (self
      reported number of teeth possessed and denture status), known confounding factors
      associated with OHQOL, those with high levels of dental anxiety (DAS > or = 15)
      were approximately two times as likely to be among those experiencing the poorest
      OHQOL (below the population median OHQoL-UK (W) score) in Britain (P < 0.001; OR
      = 1.93; 95% CI 1.41, 2.65). CONCLUSION: Dental anxiety is associated with the
      impact oral health has on life quality. Those experiencing high levels of dental
      anxiety are among those with the poorest oral health-related quality of life in
      Britain.

PMID- 14961843
TI  - The impact of childhood sexual abuse on dental fear.
AB  - OBJECTIVE: Dental fear is a risk factor for poor oral health. Thus, treatment of
      dental fear is a challenge to dentists. The consequences of childhood sexual
      abuse (CSA) may include dental fear. A history of CSA complicates dental fear
      treatment, and it is often a secret. The aim of this study was to explore
      differences in subjective evaluations of use of dental services, experiences of
      dental treatment situations, dental appearance and dental problems in women who
      report both CSA and dental fear, and women who report dental fear only. METHODS:
      In an anonymous survey, 58 women with dental fear and a history of CSA were
      compared with 25 women with dental fear without CSA. Twenty-five women without
      dental fear acted as a control group. RESULTS: No differences between dental fear
      patients with and without a history of CSA were found in subjective evaluations
      of use of dental services, dental appearance and dental problems, or in the
      scores on the Dental Fear Scale (DFS). Women who reported a history of CSA and
      dental fear had statistically significant higher scores on the Dental Belief
      Scale (DBS). CONCLUSION: The results suggest that women who report dental fear
      and a history of CSA assess interpersonal factors concerning communication,
      trust, fear of negative information and lack of control as more fear evoking than
      women who report dental fear without a history of CSA.

PMID- 14961844
TI  - The MELAS syndrome. Review of the literature: the role of the otologist.
AB  - The mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like
      episodes (MELAS) syndrome is a rare congenital disorder of mitochondrial DNA (mt
      DNA). Patients with this syndrome may present to the otolaryngologist with
      sensorineural hearing loss (SNHL), which is genetic in origin. A high index of
      suspicion is required because this hearing loss is part of a syndrome for which
      early diagnosis and intervention is required.

PMID- 14961845
TI  - Audiometric evaluation of an attempt to optimize the fixation of the transducer
      of a middle-ear implant to the ossicular chain with bone cement.
AB  - Typically, an implantable hearing device consists of a transducer that is coupled
      to the ossicular chain and electronics. The coupling is of major importance. The
      Vibrant Soundbridge (VSB) is such an implantable device; normally, the VSB
      transducer is fixed to the ossicular chain by means of a special clip that is
      crimped around the long process of the incus. In addition to crimping, bone
      cement was used to optimize the fixation in six patients. Long-term results were
      compared to those of five controls with crimp fixation alone. To assess the
      effect of bone cement (SerenoCem, Corinthian Medical Ltd, Nottingham, UK) on
      hearing thresholds, long-term post-surgery thresholds were compared to pre
      surgery thresholds. Bone cement did not have any negative effect. Next, to test
      the hypothesis that aided thresholds might be better with the use of bone cement,
      aided thresholds were studied. After correction for the severity of hearing loss,
      only a small difference was found between the two groups at one frequency, viz. 2
      kHz. It was concluded that there was no negative effect of using bone cement;
      however, there is also no reason to use bone cement in VSB users on a regular
      basis.

PMID- 14961846
TI  - Evaluation of hearing thresholds in 3-month-old children with a cleft palate: the
      basis for a selective policy for ventilation tube insertion at time of palate
      repair.
AB  - Hearing thresholds in children with a cleft palate prior to cleft palate repair
      are not widely documented, and audiological criteria for short-term ventilation
      tube insertion do not exist. The aims of this prospective study are to estimate
      hearing thresholds in 40 children with a cleft palate by 3-month developmental
      age with auditory brainstem responses (ABRs) under natural sleep and to estimate
      a hearing threshold guideline for short-term ventilation tube insertion. Our
      results show a wide range of air conduction hearing thresholds using click ABRs
      (2-4 Hz), which ranged from 25 to 102 dBnHL in the left ear and from 25 to 80
      dBnHL in the right ear with means of 53 and 49 and standard deviations of 17 and
      13 respectively. The bone conduction thresholds ranged from 0 to 55 dBnHL with a
      mean of 26 and a standard deviation of 13. Eighty-three per cent of children had
      flat, type B, on high-frequency tympanograms, indicative of middle ear effusion.
      Thirty per cent of the infants had a cleft palate associated with a known
      syndrome. Currently, it is the authors' practice to use short-term ventilation
      tubes on a selective basis at the time of cleft palate repair when there is a
      conductive hearing loss of more than 55 dBnHL in the better ear as determined by
      ABR with type B high-frequency tympanograms. This threshold level takes into
      account electrophysiological and auditory pathway maturation discrepancies. With
      this as the guideline, between 28% and 35% of the children in this study would be
      eligible for surgery. This criterion still requires further validation.

PMID- 14961847
TI  - The use of an ambulatory, automatic sleep recording device (QUISI version 1.0) in
      the evaluation of primary snoring and obstructive sleep apnoea.
AB  - Electroencephalogram (EEG) evaluation with polysomnography (PSG) according to the
      Rechtschaffen & Kales (R&K) rules is time and cost consumptive, but ambulatory
      polygraphy systems do not allow EEG recording routinely. As a consequence, the
      number of sleep disordered events cannot be calculated exactly. QUISI is a one
      channel, self-applicable ambulatory EEG recording device. The present study was
      designed as a prospective, non-randomized clinical trial. This investigation
      evaluated the results of 40 patients with primary snoring and obstructive sleep
      apnoea measured with level 1 PSG and QUISI simultaneously. Fifteen patients
      (37.5%) were primary snorers with normal sleep profiles, whereas 25 patients
      (62.5%) suffered from obstructive sleep apnoea (OSA) with a Respiratory
      Disturbance Index (RDI) of 38.6 +/- 23.8. The mean total sleeping time (TST) was
      underestimated by 4.5%, while Sleep Efficiency Index (SEI) was understimated by
      4.6% by the QUISI device compared with PSG. The correlation between the QUISI and
      the PSG estimates for single sleep stages demonstrated only moderate correlation.
      The statistical significance for sleep stage 2 was r = 0.42, P = 0.002; for sleep
      stage 3/4, r = 0.31, P = 0.02; and for WAKE, r = 0.33, P = 0.01. Sleep stage 2 as
      well as sleep stage 3/4 were underestimated by QUISI substantially (difference: 
      5.6% and -10.3%), while WAKE was overestimated by QUISI to a larger amount
      (difference: +10.4%). Sensitivity and specificity of QUISI to recognize
      pathological sleep profiles compared with PSG/R&K were 0.92 and 0.96
      respectively. QUISI is able to evaluate normal versus altered sleep profiles in
      patients with primary snoring and OSA. Comparing the quartile ranges, we found
      substantial differences between QUISI and PSG/R&K. QUISI gives an impression of
      sleep architecture and objective verification of a sleep disturbance in an
      ambulant setting but cannot replace the sleep laboratory-based PSG.

PMID- 14961848
TI  - The effect of temperature, humidity and peak inspiratory nasal flow on olfactory
      thresholds.
AB  - Temperature, humidity and nasal peak inspiratory flow rate (PIFR) are potential
      variables in the quantitative measurement of olfactory thresholds in the clinic.
      To date, these variables have not been properly evaluated with respect to
      olfactory perception, and therefore the aim of this study was to determine their
      effect on the thresholds. These variables were measured on 10 occasions in 10
      subjects over a 10-week period. The results obtained were then subjected to
      statistical analysis using a linear mixed-effect model. This demonstrated that
      olfactory thresholds are sufficiently independent of room temperature, peak
      humidity and nasal PIFR in a routine outpatient clinic environment in normal
      subjects, with no evidence of any statistically significant influence by these
      variables.

PMID- 14961849
TI  - Paediatric rhabdomyosarcoma of the ear and temporal bone.
AB  - The objective of the present study was to review the presentation, management,
      outcome and morbidity of paediatric patients presenting to a single centre with
      rhabdomyosarcoma of the ear and temporal region. All patients diagnosed with
      rhabdomyosarcoma of the ear and temporal region between 1980 and 2000 were
      entered into this retrospective study. Fourteen patients were identified. The
      median age at presentation was 4.5 years with a mean time of onset of symptoms to
      diagnosis of 21 weeks. In many patients, the presentation mimicked that of
      chronic otitis media, delaying diagnosis. Histological subtype was embryonal in
      13 patients and alveolar in 1. All patients underwent multimodality treatment.
      The 5-year disease-free survival rate was 81%. Regional post-treatment morbidity
      included chronic aural discharge (6/14), facial palsy (8/14), growth disturbance
      (4/14) and maxillo-facial deformity occurring in four children. From the results,
      we conclude that these patients should usually present to an ENT surgeon who
      should keep the diagnosis in mind when dealing with children with chronic otitis
      media as early diagnosis with referral to a specialist multidisciplinary team
      will optimize the chance of survival. Discharge, hearing loss and aural polyp,
      although commonly because of chronic otitis media, should prompt urgent
      investigation and biopsy, particularly if associated with facial palsy,
      lymphadenopathy or an obvious mass.

PMID- 14961850
TI  - Is otitis media with effusion a biofilm infection?
AB  - Recent attention has focused on the possibility that otitis media with effusion
      (OME) may represent a chronic infective state such as those evidenced in
      conditions secondary to biofilms or small colony variants. This review discusses
      the evidence suggesting that this may indeed be the case and explains why this
      may prove to be important in the future management of this condition by
      discussing recent advances in understanding these bacterial phenotypic variants.

PMID- 14961851
TI  - Is pseudosulcus alone a reliable sign of gastroesophago-pharyngeal reflux?
AB  - To investigate if laryngeal pseudosulcus (bilateral infraglottic oedema) is a
      reliable sign of pharyngeal reflux, the video recordings of 59 patients and 18
      controls were examined off-line by two phoniatricians. Eleven video segments were
      duplicated for calculation of intrarater reliability. The frequency of
      pseudosulcus was correlated to the results of 24-h double-probe pH monitoring.
      The intrarater reliability was moderate (K = 0.582; P = 0.005). The sensitivity
      of pseudosulcus in the diagnosis of pharyngeal reflux among the patients was 30%
      and among the controls it was 0%. The positive predictive value (PPV) of
      pseudosulcus for patients with pharyngeal and laryngeal symptoms was 67%, while
      for the controls it was 0%. The negative predictive value (NPV) of pseudosulcus
      for patients with pharyngeal or laryngeal symptoms was 32% and for the controls
      it was 64%. The single finding of pseudosulcus is not a very sensitive predictor
      of pharyngeal reflux but if the patient has laryngeal symptoms and a pseudsulcus,
      the probability that the patient has pharyngeal reflux is almost 70%.

PMID- 14961852
TI  - The combined endoscopic CO(2) laser posterior cordectomy and total
      arytenoidectomy for treatment of bilateral vocal cord paralysis.
AB  - Upper airway obstruction, because of bilateral vocal cord paralysis, presents a
      serious challenge to the Otolaryngologist. Various surgical techniques have been
      advocated for the management of patients with vocal cord paralysis. Among these
      techniques, the individual use of laser CO(2) arytenoidectomy and posterior
      cordotomy has gained wide acceptance. In this report, we describe our experience
      in the management of bilateral vocal cord paralysis by combining posterior
      partial cordotomy as described by Dennis and Kashima, with total arytenoidectomy
      as described by Ossoff et al. We report the long-term results in the management
      of 18 patients treated in our department during the last 8 years.

PMID- 14961853
TI  - Bcl-Xl protein expression in laryngeal squamous cell carcinoma.
AB  - The Bcl-2 family of proteins regulate one of the steps in an evolutionary
      conserved apoptotic pathway. The long splice variant of Bcl-X (Bcl-Xl) is a
      potent antagonist of apoptosis. The aim of the study was to evaluate the relation
      between the presence of immunohistochemically detectable Bcl-Xl protein in
      laryngeal squamous cell carcinomas (LSCCs) and clinicopathological data, as well
      as DNA ploidy status and proliferative activity. In 50 specimens of LSCC, Bcl-Xl
      protein expression was evaluated immunohistochemically. Proliferative activity
      (SG2M-phase index) and DNA ploidy were measured by flow cytometry. In our study,
      Bcl-Xl protein expression decreased with decreasing tumour differentiation (P =
      0.04). The majority of patients with Bcl-Xl protein immunoreactivity had no
      metastatic lymph node involvement (P = 0.01). Other factors such as age, gender,
      primary tumour size (pT) and type of cancer (keratinizing/non-keratinizing) were
      not associated with Bcl-Xl protein level. There was no correlation between Bcl-Xl
      protein and SG2M-phase index or DNA ploidy status. Our findings show that
      expression of Bcl-Xl protein is increased in a great fraction of laryngeal
      cancers. Further studies, however, are needed to clarify association between Bcl
      Xl protein expression and clinical course of patients.

PMID- 14961854
TI  - Recurrent and prolonged frontal sinusitis.
AB  - The purpose of the study was to find the factors that predict the prolongation or
      recurrence of frontal sinusitis, to analyse the results of endoscopic surgery and
      trephination and also to analyse the value of the clinical estimation made by the
      treating specialist. The study was partly prospective, partly retrospective, and
      it was carried out in 1995-97. The follow-up continued until the end of 1998. The
      sample consisted of 456 patients (264 men and 192 women) treated for acute
      frontal sinusitis in Turku University Central Hospital. The collected information
      consisted of patient history, treatment, outcome and possible re-operations. To
      be able to evaluate conservative treatment in relation to operative treatment in
      patients with prolonged disease, a matched conservatively treated patient was
      selected for each endoscopically operated patient. Of the 456 patients, 359
      healed normally, 85 developed prolonged disease, while recurrences were found in
      50 patients. Endoscopic surgery was performed in 35 patients. The mean time
      interval between the endoscopic sinus operation (FESS) and healing was 8.2 weeks.
      Trephination was performed in 52 patients and FESS in 35 patients. In the
      statistical analysis, the factors having significance in predicting the outcome
      of the disease were, in the bivariate analysis, atopy and type of primary
      operation, chronic rhinitis, polyps, type of previous operations and of re
      operations. Neither trephination nor FESS proved markedly better than the other
      one. Our conclusion was that the prognosis of frontal sinusitis is difficult to
      predict with any single factor, but is affected by many of them.

PMID- 14961855
TI  - Self-assessment of voice therapy for chronic dysphonia.
AB  - The effects of voice therapy in a group of chronically dysphonic patients are
      determined using two quality-of-life (QOL) instruments: the Voice Handicap Index
      (VHI), and a simple three-item outcome scale (three visual analogue scales). Both
      instruments measure changes in the quality of the voice itself and in the extent
      of impairment resulting from the dysphonia as experienced by the patient in
      social and occupational settings. Statistical tests conducted on pre- and post
      treatment data indicated significant improvements on both instruments for the
      group as a whole. At the individual level, however, the effects were diverse. For
      roughly 50% of the subjects, a significant improvement could be established. The
      positive changes as measured with the three-item scale were greater than those
      measured with the VHI. The results suggest that the two QOL instruments measure
      slightly different aspects of the subjective perception of the therapy effects.
      In order to obtain a general evaluation of the patient's handicap, it may suffice
      to ask some simple questions.

PMID- 14961856
TI  - Hearing thresholds in patients affected by rheumatoid arthritis.
AB  - The aim of the study was to evaluate hearing thresholds in 38 patients with
      rheumatoid arthritis, divided according to disease activity into active (group A,
      n = 20) and non-active (group B, n = 18) patients. Pure tone audiometry,
      tympanometry and complete rheumatological assessment were performed. All patients
      presented poorer auditory thresholds compared with controls. Patients of group A
      had both air and bone conduction thresholds poorer than group B (although not
      statistically significant), and most patients of both groups presented an air
      bone (a-b) gap. No significant difference in middle ear pressure was noticed
      between patients and controls. No correlation between hearing impairment and
      duration of the disease or patients' age was found. The high prevalence of
      hearing loss in autoimmune diseases supports the importance of audiometric
      evaluation in such patients. The auditory recovery through middle ear surgery
      before cranial nerve involvement could be considered in selected patients.
      Further investigations are needed for a better knowledge of the middle and inner
      ear involvement in patients with rheumatoid arthritis.

PMID- 14961857
TI  - The effect of replacement fluids and normovolaemic haemodilution on the survival
      of dorsal skin flaps in rats.
AB  - The objective of this study is to investigate the effect of normovolaemic
      haemodilution (anaemia), haemoglobin level and replacement fluids on the survival
      of local flaps in rats. Fifty male Wistar rats were divided into four study
      groups and one control group (10 rats for each). In the study groups, 20% or 30%
      of blood was withdrawn and replaced by either Gelofusine or saline (0.9%). Single
      1.5 cm x 3 cm cranially based dorsal random skin flaps consisting of skin and
      panniculus carnosus were elevated in all rats. No difference was determined
      between the control and 20% exsanguinated groups regarding flap survival area.
      There was a statistically significant difference between the flap survival areas
      of 20% exsanguinated groups and 30% exsanguinated groups. If the blood loss
      exceeds 30% of total volume and/or haemoglobin (Hb) level is lower than 10.72
      g/dL, the risk of flap necrosis increases significantly.

PMID- 14961858
TI  - Is clinical otolaryngology publishing patient-centred research?
AB  - We asked how patient centred is Clinical Otolaryngology? Using two new models for
      analysing the patient-centredness of medical literature, three reviewers
      classified 176 papers (91 articles and 85 abstracts) published in this journal
      during the year 2000. Patients appeared as clinical subjects in 98 (56%), were
      interviewed by closed questionnaires in 21 (12%) and open questionnaires in 6
      (3%), represented only by demographic details in 40 (23%) and not part of the
      study in 11 (6%) of papers. Papers were considered to address a biomedical frame
      of reference in 48 (27%), the patient's frame of reference in 6 (3%), technical
      aspects of the clinical encounter in 109 (62%) and communicative aspects in 7
      (4%), and the setting for the encounter in 6 (3%) of papers. We show that some
      patient-centred research is published in Clinical Otolaryngology but suggest that
      it could publish more.

PMID- 14961859
TI  - Growth rate of non-vestibular intracranial schwannomas.
AB  - A group of nine patients with non-vestibular intracranial neuromas (four jugular,
      four facial, one trigeminal) underwent an interval scanning management policy,
      with serial annual magnetic resonance (MR) imaging. Tumour volume was assessed by
      manual measurement of the tumour area by MR imaging. Tumour volume was assessed
      by manual measurement of the tumour area on MR imaging axial cuts. The mean
      tumour size at presentation was 4.6 cm(3) (range 0.7-17.8 cm(3)). During a mean
      follow-up of 36 months (range 22-50 months), five out of nine tumours grew
      significantly at a rate of more than 5% of their initial volume per year. Only
      those tumours growing at a rate of more than 20% initial volume per year
      exhibited symptom progression. During a 36-month period of interval scanning,
      just over 50% of non-vestibular intracranial neuromas exhibited significant
      growth. Symptom progression was found to be a strong indicator of a high growth
      rate. This proportion exhibiting growth is higher than that demonstrated by
      unilateral sporadic vestibular schwannomas, but less than in patients with
      neurofibromatosis II. Early treatment of non-vestibular intracranial neuromas
      should therefore be considered.

PMID- 14961860
TI  - The demand for evening ENT out-patient appointments.
AB  - Increasing patient choice is a major theme of the NHS plan. For clinicians, this
      may mean offering NHS out-patient services at unfamiliar times, such as evenings
      or weekends. Published surveys of patients' views generally show high levels of
      satisfaction with appointments between 9 am and 5 pm, although there is a cohort
      of younger, employed patients who have expressed interest in evening clinics.
      This study attempted both to quantify the demand for evening ENT clinics and to
      target the patient group most likely to take up the offer of an evening
      appointment. When surveyed, approximately one-quarter of four hundred and fifty
      out-patients stated they would have preferred an evening appointment. However,
      when this group was targeted and formally offered a choice of time, only 1% of
      patients tried to change from daytime to evening. There is effectively no demand
      amongst NHS patients for ENT evening out-patient clinics.

PMID- 14961862
TI  - Achieving early surgery for undescended testes: quality improvement through a
      multifaceted approach to guideline implementation.
AB  - BACKGROUND: Surgery for undescended testes is recommended before the age of 2
      years. However, boys are still undergoing surgery for undescended testes at a
      much later age than recommended. METHODS: An initial audit reviewed all
      orchidopexies performed at Northampton General Hospital between 1992 and 1994.
      This demonstrated that only 19% of boys had surgery by the age of 2 years, and
      the key reason for late surgery was late referral. Guidelines for referral of
      undescended testes were established in which referral to a surgeon was advised
      following the 8-month child health surveillance check if undescended testis was
      suspected. This would enable surgery before the age of 2 years. Audit results
      were disseminated and we implemented a package of measures based on evidence
      based change management techniques. These included written advice to general
      practitioners (GPs), a parent information leaflet and an amended personal child
      health record advising timing of referral. A reminder to the GP to refer
      following the 8-month check was generated using computer recall from the Child
      Health System records. Guideline implementation was monitored by annual audit and
      feedback. RESULTS: The baseline audit for the years 1992-94 found a median age at
      surgery of 4 years. Implementation of the new policies in 1998 resulted in a
      reduction in median age at surgery to 2.0 years in the 12 months ending September
      2001. CONCLUSIONS: While concern about the age at orchidopexy has been
      highlighted in many previous studies, this is the first to show that improvement
      in the age at orchidopexy can be achieved. Implementing locally agreed guidelines
      with written information to GPs and parents combined with computerized recall
      from Child Health System records achieved the target within 3 years. Similar
      systems could be implemented nationally at minimal cost.

PMID- 14961863
TI  - The role of emotional social support in the psychological adjustment of siblings
      of children with cancer.
AB  - BACKGROUND: Siblings of children with cancer are at risk for reduced emotional
      support. The role of emotional social support in the psychological adjustment of
      siblings of paediatric cancer patients was examined, in the context of age and
      gender. METHODS: The sample consisted of two groups of siblings of children being
      treated for cancer: siblings referred for behaviour problems (n = 47) and a
      comparison group of non-referred siblings (n = 25). Forty-two were female, and 30
      were male. The mean age was 10.31 years (SD = 2.71). Siblings completed measures
      of depression, anxiety, behaviour, and emotional social support. One parent of
      each sibling completed measures of sibling's behaviour and anxiety. RESULTS:
      Siblings who reported more social support endorsed significantly fewer symptoms
      of depression, anxiety, and fewer behaviour problems, and their parents reported
      less anxiety and fewer behaviour problems than siblings who reported lower social
      support. Parents of referred siblings reported significantly more behaviour
      problems than parents of non-referred siblings. Referred adolescent females
      reported significantly higher depression scores and were perceived as more
      anxious than referred adolescent males and non-referred adolescent females. Non
      referred younger siblings with high social support were perceived by their
      parents as having the fewest behaviour problems. CONCLUSIONS: High level of
      social support appears to play a protective role in psychological adjustment of
      siblings of paediatric cancer patients, with age and gender as modifying factors.
      Although not all siblings develop behaviour or emotional problems, it is critical
      to identify those who do in order to intervene accordingly.

PMID- 14961864
TI  - 'I was running away from death'- the pre-flight experiences of unaccompanied
      asylum seeking children in the UK.
AB  - OBJECTIVE: To collect information about the pre-flight experiences of
      unaccompanied asylum seeking children (UASC) in the UK to increase the
      understanding of support needed on arrival in the UK. METHODS: Retrospective
      social services case file and legal statement review and semi-structured in-depth
      interviews with 100 UASC. RESULTS: Nearly half of all UASC have experienced
      separation from or loss of parents and/or family members (47%), and a further 41%
      had personally experienced or witnessed violence. Sexual violence (such as rape)
      was reported by 24% of African girls. Many children reported complex journeys to
      the UK. CONCLUSIONS: UASC arrive in the UK with a variety of potentially
      traumatic experiences. Whilst research is starting to identify some of the
      experiences of UASC, further culturally appropriate research is needed to
      identify their health and social needs after arrival. Further research will help
      to identify the specific experiences of UASC, indicating where services should be
      improved to deal with their complex and diverse needs.

PMID- 14961865
TI  - Measure of Processes of Care (MPOC) applied to measure parent's perception of the
      habilitation process in Sweden.
AB  - AIM: To evaluate the instrument Measure of Processes of Care (MPOC) in a Swedish
      context. METHODS: The MPOC consists of 56 questions in the five scales: enabling
      and partnership; providing general information; providing specific information
      about the child; co-ordinated and comprehensive care; and respectful and
      supportive care. The questionnaire was translated into Swedish and distributed to
      850 families, served by four habilitation centres. After two reminders, a
      response rate of 74.9% was obtained, and about 60% of the questionnaires
      qualified for further statistical analysis. Reliability, calculated as Cronbach's
      alpha, was high for four of the five scales and acceptable for the fifth (scale
      no. 3). RESULTS: Significant differences were shown between centres as well as
      between age groups. These differences were reasonable as judged through
      background knowledge, indicating that the instrument was able to discriminate
      between actual differences in services. Commenting on the practical use of the
      questionaire, staff, as well as responding parents, found the questionnaire
      rather long and some parents reported difficulties in giving answers as specific
      as the questionnaire asked them to. CONCLUSION: The MPOC shows sufficient
      sensitivity to be used as an evaluation tool for services at a centre or program
      level, and can be recommended for research and practical use.

PMID- 14961866
TI  - Sleep problems in children with an intellectual disability: parental perceptions
      of sleep problems, and views of treatment effectiveness.
AB  - BACKGROUND: Sleep problems are common in children with an intellectual disability
      (ID), often lasting for many years. Many parents do not perceive their child to
      have a sleep problem, do not believe treatment is possible and do not seek
      treatment. This paper examined prevalence and duration of sleep problems in
      children with an ID and considered parental perceptions of sleep problems and
      views towards treatment. METHOD: The paper reports on two studies (n = 149 and
      243 respectively) of children between 3 and 18 years, with a range of
      disabilities. Parents in each study completed a questionnaire about their child's
      sleep problems, and the type and effectiveness of any treatment used to address
      their child's sleep problems. RESULTS: Prevalence rates ranged between 25.5% and
      36.2% for sleep problems with an average duration of between 6 and 9 years.
      Around half of parents had sought treatment for their child's sleep problem in
      Study 1, while 76% had done so in Study 2. Parental ratings regarding treatment
      effectiveness were higher in Study 1 than in Study 2. Contrary to expectations,
      behavioural treatment was not rated as significantly more effective than other
      treatments in either study. CONCLUSIONS: While sleep problems are common and
      chronic in children with an ID, parents may not recognize a sleep problem as
      present, often do not seek treatment for their child's sleep problems, and
      treatment advice and effectiveness is very variable. Thus, further research and
      parent and professional education regarding the identification and treatment of
      sleep problems in these children is required.

PMID- 14961867
TI  - What influences physiotherapy use by children with cerebral palsy?
AB  - AIM: To investigate factors that influence the frequency of physiotherapy
      currently used by a population of children with moderate to severe cerebral palsy
      (CP). METHODS: A survey using a postal questionnaire was sent to 212 parents of
      children with moderate to severe CP. The families were identified from a
      geographically defined case register of children with CP in Northern Ireland (the
      Northern Ireland Cerebral Palsy Register). Eighty-five per cent of parents
      responded. One-third of parent responses regarding their child's use of
      physiotherapy were validated with their child's physiotherapist and the level of
      agreement was high. RESULTS: Ninety-four per cent (169/180) of children received
      conventional physiotherapy from a statutory source during the school term. Of
      these, 61% (104/169) used 'intense' levels of physiotherapy (defined as at least
      twice a week). A higher proportion of intense users were children with severe CP
      compared with moderate CP (69% vs. 47%; P < 0.01); with moderate intellectual
      impairment (IQ </= 70 > 50) compared with severe (IQ </= 50) or no intellectual
      impairment (IQ > 70) (81% vs. 64% vs. 39% respectively; P < 0.01) and at schools
      for physical disability (PD) compared with severe learning disability (SLD) or
      mainstream (MS) schools (82% vs. 66% vs. none respectively; P < 0.001). After
      controlling for severity of motor impairment and the presence and severity of
      intellectual impairment, children with CP at MS schools used on average
      significantly less physiotherapy compared with children with similar levels of
      motor impairment at PD schools (P < 0.001). CONCLUSIONS: Children with CP in MS
      schools use less physiotherapy compared with children with similar levels of
      disability in special schools. Organizing services around special schools may
      limit the degree to which children with CP and other disabilities are
      successfully integrated into MS education.

PMID- 14961868
TI  - The potential of emergency department injury surveillance data: an illustration
      using descriptive analysis of data in 0-4 year olds from the Bath injury
      surveillance system.
AB  - OBJECTIVES: To illustrate the potential of injury surveillance data from an
      emergency department surveillance system. SETTING: Bath clinical area. METHODS:
      Data for children (0-4 years old) resident in Bath city in UK were recoded and
      analysed. RESULTS: There were a total of 3144 attendances and 2300 unintentional
      injuries - equivalent to an attendance rate of 131/1000. There were 91 thermal
      injuries and 162 poisoning/ingestions. Descriptive information is presented on
      the circumstances and consequences. CONCLUSION: The majority of unintentional
      injuries in 0-4 year olds occur in the home, which is a modifiable environment.
      Detailed information around the circumstances available from the Bath injury
      surveillance system allows better focus for prevention messages and priority
      setting.

PMID- 14961869
TI  - Are foster parents reliable informants of children's behaviour problems?
AB  - BACKGROUND: Clinicians and researchers primarily measure behavioural and
      emotional problems of children in foster care from carer-report checklists. Yet
      the reliability of these reports is not adequately established. The present study
      examines one indicator of reliability for foster parent checklist reports:
      interrater agreement between foster parents and teachers. METHODS: Estimates of
      interrater agreement of foster parent and teacher responses on the cross
      informant scales of the Child Behaviour Checklist (CBCL) and the Teacher Report
      Form (TRF) were obtained for 47 children in long-term foster care, aged 5-11
      years. The estimates included calculations of agreement for continuous measures
      of problem behaviour, as well as for categorical determinations of clinically
      significant behaviour. RESULTS: Correlations of CBCL and TRF mean raw scores for
      the total problems (r = 0.71) and externalizing (r = 0.78) scales exceeded those
      described in prior studies of parent-teacher agreement, while correlation for
      internalizing scores (r = 0.23) was similar to that found previously. Teachers
      and foster parents demonstrated moderate to good agreement (kappa = 0.70-0.79) in
      identifying clinically significant total problems and externalizing problems, but
      poor agreement in identifying internalizing problems. CONCLUSIONS: Discrepancies
      between these and prior findings are discussed. For children in long-term foster
      care, foster parents or teachers may be used as informants for total problems,
      externalizing problems, and social-attention-thought problems. The reliability of
      data on internalizing symptoms is less certain.

PMID- 14961870
TI  - Comparing specialist early years provision for speech and language impaired
      children with mainstream nursery provision in the UK - an application of the
      Early Childhood Environment Rating Scale (ECERS).
AB  - BACKGROUND: This study examines the application of the Early Childhood
      Environment Rating Scale (ECERS) to specialist early years provision for children
      with developmental speech and language impairment. The scale, which has been used
      in the national Effective Provision of Pre-school Education (EPPE) study in the
      UK comprises seven subscales describing the quality of provision along a
      continuum centred on the following areas: 'space and furnishings', 'personal care
      routines', 'language reasoning', 'activities', 'interaction', 'program
      structure', and 'parents and staff'. METHODS: The ECERS was applied to two
      nurseries funded by the UK charity I CAN by two researchers with inter-rater
      reliability coefficients ranging from 0.91 to 0.96. RESULTS: There were notable
      differences between the specialist early years provision and 'average' nursery
      provision in the UK. On 7/8 measures the early years centre scores are markedly
      higher than average pre-school provisions. The standard of education and care for
      the pre-school provisions included in the EPPE project ranged from below minimal
      (for the diversity subscale, ECERS-E) to approaching good (for the space and
      furnishings subscale). In contrast, the early years centres were rated as between
      minimal to good on areas such as space and furnishings and good to excellent on
      all other areas. CONCLUSIONS: Clearly specialist services such as those described
      offer something different from the average. Given results which suggest the
      positive effects on the children's language abilities of such services it is
      quite possible that the distinctive characteristics of the nursery environment
      are responsible for the positive impact. There is a good case for extending the
      application of the ECERS as a way of helping those providing specialist services
      start to detect the active ingredients of the provision.

PMID- 14961877
TI  - NICE fertility guideline: good news for infertile couples, but who pays the bill?

PMID- 14961878
TI  - The Baby Friendly Hospital Initiative: where next?

PMID- 14961879
TI  - The importance of genetic and environmental effects for pre-eclampsia and
      gestational hypertension: a family study.
AB  - OBJECTIVES: To determine the importance of genetic effects in the aetiology of
      pre-eclampsia and gestational hypertension and to investigate whether pre
      eclampsia and gestational hypertension share genetic aetiology. DESIGN:
      Individual record linkage between the population-based Swedish Multi-Generation
      and the Medical Birth Registers. SETTING: Sweden. POPULATION: 1,188,207 births
      between 1987 and 1997 and their parents. METHODS: Similarities in relatives were
      measured by the number of pairs concordant and discordant for disease, the odds
      ratio (OR) and tetrachoric correlations. Estimates of genetic and environmental
      effect for gestational hypertension, pre-eclampsia and pregnancy-induced
      hypertension were calculated from structural equation model fitting. MAIN OUTCOME
      MEASURES: Pre-eclampsia and gestational hypertension. RESULTS: Full sisters and
      mother-daughters were more similar for pre-eclampsia (OR 3.3, 95% confidence
      interval [CI] 3.0-3.6 and OR 2.6, 95% CI 1.6-4.3, respectively) than half-sisters
      (maternal half-sisters OR 1.4, 95% CI 0.9-2.2 and paternal half-sisters OR 1.0,
      95% CI 0.6-1.6). Full sisters and mother-daughters were also more similar for
      gestational hypertension than half-sisters. A full sister to a woman with pre
      eclampsia also had a significantly increased risk of gestational hypertension (OR
      2.5, 95% CI 2.2-2.8). In contrast, the risk for half-sisters was not increased.
      Model fitting suggested heritability estimates for pre-eclampsia of 31%, for
      gestational hypertension 20% and for pregnancy-induced hypertension 28%.
      CONCLUSIONS: There is a genetic component in the development of pre-eclampsia and
      gestational hypertension and the pattern of co-morbidity suggests that they may
      share part of their genetic aetiology. This could be important for studies of
      potential susceptibility genes for these diseases.

PMID- 14961880
TI  - Thiol status and antioxidant capacity in women with a history of severe pre
      eclampsia.
AB  - OBJECTIVE: To investigate a possible mechanism that could lead to the subsequent
      development of cardiovascular diseases (CVD) in women with a history of severe
      pre-eclampsia. DESIGN: Case-control study. SETTING: University Medical Centre
      Nijmegen, The Netherlands. SAMPLE: Non-pregnant women with a history of severe
      pre-eclampsia (n= 131) and women with an uncomplicated obstetric history (n= 94).
      METHODS: Total plasma levels of cysteine (tCys), homocysteine (tHcy),
      cysteinylglycine (tCysGly) and glutathione (tGSH), the free-to-oxidised ratio of
      these thiols in whole blood, the glucose-6-phosphate dehydrogenase (G6PDH) enzyme
      activity and antioxidant capacity were assessed at least 6 months following last
      pregnancy. MAIN OUTCOME MEASURE: Oxidative stress and antioxidant status.
      RESULTS: Women with a history of severe pre-eclampsia showed higher levels (mean
      [SD]) of tHcy (13.1 [5.0] versus 11.5 [4.8] micromol/L; P= 0.018) and tCysGly
      (37.5 [5.6] versus 34.0 [5.8] micromol/L; P= 0.0001) compared with controls,
      whereas tCys was lower (232 [31] versus 242 [39]; P= 0.029). The lower free-to
      oxidised ratio of homocysteine (2.3 [0.8] versus 2.9 [1.0], P= 0.0001) among
      women with a history of severe pre-eclampsia as compared with control subjects
      might indicate a higher oxidant status for homocysteine. Previous severe pre
      eclamptic patients had also a higher antioxidant capacity as compared with
      controls (0.79 [0.14] versus 0.74 [0.11] mmol Fe2+/L, P= 0.002). CONCLUSION:
      Since women with a history of severe pre-eclampsia showed elevated total
      homocysteine levels, which is an independent risk factor for CVD, and higher
      oxidised homocysteine levels in whole blood, these women may have an enhanced
      risk for the subsequent development of cardiovascular-related problems in later
      life.

PMID- 14961881
TI  - How should randomised trials including multiple pregnancies be analysed?
AB  - OBJECTIVE: To compare the effects of four methods of analysis on the results of
      randomised controlled trials that recruit women with multiple pregnancies and
      measure outcomes on their babies. DESIGN: Analysis of one real and two simulated
      data sets. SETTING: Secondary analysis of perinatal randomised controlled trials.
      POPULATION: Randomised controlled trials including women with multiple
      pregnancies. METHODS: The analytical methods compared were (a) assuming
      independence among babies, (b) analysing outcomes per women, counting a woman as
      having an outcome if any of her babies had it (equivalent to selecting the worst
      outcome among any of a woman's babies), (c) randomly selecting one baby from each
      set of multiples for inclusion in the analysis, (d) adjustment of the analysis to
      take account of non-independence of babies from multiple pregnancies, using
      methods developed for analysis of cluster randomised trials. MAIN OUTCOME
      MEASURES: Odds ratios for trials' main outcomes. RESULTS: Results from
      application of cluster trial methods were similar to those from assuming
      independence among babies, but with slightly wider confidence intervals,
      reflecting the reduced effective sample size caused by non-independence between
      babies from the same pregnancy. Results were more variable using the other two
      methods, and in some cases, departed markedly from the results of the cluster
      trial methods. CONCLUSIONS: Cluster trial methods provide a simple way of
      adjusting the analysis to take account of non-independence between babies from
      the same pregnancy. Random selection and analysis by pregnancy (methods (b) and
      (c)) have disadvantages and do not report outcomes for all of the babies in the
      trial. This may cause problems with incorporating trials analysed using these
      methods into systematic reviews.

PMID- 14961882
TI  - Isolated oligohydramnios is not associated with adverse perinatal outcomes.
AB  - OBJECTIVE: To examine fetal growth and perinatal outcomes in pregnancies with
      isolated oligohydramnios. DESIGN: A cohort study. SETTING: Multiple clinics and
      hospitals. POPULATION: Low risk pregnant women. METHODS: We used data from the
      multicentre clinical trial of Routine Antenatal Diagnostic Imaging with
      UltraSound (RADIUS), in which 15,151 low risk pregnant women were randomly
      assigned to the ultrasound screening group or the control group. Women in the
      screening group underwent sonographic exams at 15-22 and 31-35 weeks of
      gestation. Both groups could have clinically indicated sonographic exams at any
      time. MAIN OUTCOME MEASURES: We used changes of fetal weight z-score to assess
      whether fetal growth was compromised from the diagnosis of oligohydramnios until
      delivery, using a repeated-measures regression. We used a combined perinatal
      index as an indicator of adverse perinatal outcome, which consisted of severe
      perinatal morbidity and mortality. RESULTS: Oligohydramnios (amniotic fluid index
      < or =5 cm) was diagnosed in 1.5% (113/7617) of women with ultrasound screening
      compared with 0.8% (57/7534) among the controls. Approximately half of the
      oligohydramnios cases in the screening group were isolated with no clearly
      associated factors (e.g. premature rupture of the fetal membranes, congenital
      anomalies, diabetes, hypertension, postdate and intrauterine growth restriction).
      Fetal weight centiles in isolated oligohydramnios cases did not change
      significantly from diagnosis until delivery. Pregnancies with isolated
      oligohydramnios had perinatal outcomes similar to pregnancies with a normal
      amniotic fluid index. CONCLUSION: Isolated oligohydramnios is not associated with
      impaired fetal growth or an increased risk of adverse perinatal outcomes.

PMID- 14961883
TI  - Antenatal screening and intrapartum management of Group B Streptococcus in the
      UK.
AB  - OBJECTIVE: To determine whether there has been any change in UK policy for the
      screening and intrapartum management of Group B Streptococcus in pregnancy over a
      two year period. DESIGN: Two national survey's of practice carried out in 1999
      and 2001. SETTING: All obstetric units in the UK. POPULATION: Clinical directors
      of maternity services. METHODS: A questionnaire was sent to all clinical
      directors of maternity services in the UK requesting information about their
      policy and practice with respect to antenatal screening for Group B Streptococcus
      colonisation. Reminders were sent after one month. MAIN OUTCOME MEASURES: Number
      of maternity units in the UK screening and offering intrapartum antibiotic
      prophylaxis for Group B Streptococcus colonisation in pregnancy. RESULTS: The
      response rates were 84% in 1999 and 82% in 2001. Of the responding units, six
      (3%) in 1999 and four (2%) in 2001 used vaginal swab based screening for Group B
      Streptococcus colonisation in the antenatal period. In 1999, intrapartum
      antibiotic prophylaxis was offered to women with a previous baby affected by
      Group B Streptococcus in 85% (176/207) of maternity units and in 2001 this had
      risen to 95% (193/203). Similarly, in 1999 intrapartum antibiotic prophylaxis was
      offered to women who were known carriers of Group B Streptococcus in 87%
      (179/207) of maternity units and in 2001 this had risen to 95% (193/203).
      Appropriate dosage of a recommended antibiotic was prescribed in 7% (9/123) units
      in 1999 and in 20% (35/178) units in 2001. CONCLUSIONS: Although intrapartum
      antibiotic prophylaxis for women at high risk of giving birth to babies with
      Group B Streptococcus is widely practiced in the UK, a programme of antenatal
      screening for Group B Streptococcus colonisation has not been adopted along the
      lines advocated in the USA. There therefore remains an opportunity to evaluate
      such a screening programme in a randomised trial.

PMID- 14961884
TI  - Maternal morbidity during labour and the puerperium in rural homes and the need
      for medical attention: A prospective observational study in Gadchiroli, India.
AB  - OBJECTIVES: To estimate the incidence of maternal morbidity during labour and the
      puerperium in rural homes, the association with perinatal outcome and the
      proportion of women needing medical attention. DESIGN: Prospective observational
      study nested in a neonatal care trial. SETTING: Thirty-nine villages in the
      Gadchiroli district, Maharashtra, India. SAMPLE: Seven hundred and seventy-two
      women recruited over a one year period (1995-1996) and followed up from the
      seventh month in pregnancy to 28 days postpartum (up to 10 visits in total).
      METHODS: Observations at home by trained village health workers, validated by a
      physician. Diagnosis of morbidities by computer program. MAIN OUTCOMES: Direct
      obstetric complications during labour and the puerperium, breast problems,
      psychiatric problems and need for medical attention. RESULTS: The incidence of
      maternal morbidity was 52.6%, 17.7% during labour and 42.9% during puerperium.
      The most common intrapartum morbidities were prolonged labour (10.1%), prolonged
      rupture of membranes (5.7%), abnormal presentation (4.0%) and primary postpartum
      haemorrhage (3.2%). The postpartum morbidities included breast problems (18.4%),
      secondary postpartum haemorrhage (15.2%), puerperal genital infections (10.2%)
      and insomnia (7.4%). Abnormal presentation and some puerperal complications
      (infection, fits, psychosis and breast problems) were significantly associated
      with adverse perinatal outcomes, but prolonged labour was not. A third of the
      mothers were in need of medical attention: 15.3% required emergency obstetric
      care and 24.0% required non-emergency medical attention. CONCLUSIONS: Nearly 15%
      of women who deliver in rural homes potentially need emergency obstetric care.
      Frequent (43%) postpartum morbidity, and its association with adverse perinatal
      outcome, suggests the need for home-based postpartum care in developing countries
      for both mother and baby.

PMID- 14961885
TI  - Uterine artery embolisation for symptomatic fibroids: the effect of the large
      uterus on outcome.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of uterine artery
      embolisation (UAE) in myomatous uteri larger than 24 week's gestation (780 cm3).
      DESIGN: Prospective case control study. SETTING: Universitas Hospital, University
      of the Free State, Bloemfontein, South Africa. POPULATION: Sixty-one women, who
      underwent UAE, were included in the study. The study group comprised of 12 women
      with uteri > or =780 cm3 and the control group 49 women with uteri <780 cm3.
      METHODS: UAE was performed and the difference in outcome for the two groups was
      determined at 12 months. MAIN OUTCOME MEASURE: Symptomatic improvement with
      embolisation of the large uterus. RESULTS: Reduction of dysmenorrhoea,
      menorrhagia and pressure effects was similar for both groups. The median
      reduction in uterine volume (pre- to post-embolisation) was 188 cm3 (range 28
      2038 cm3) with a 95% CI for the median difference for paired data of 146.5 and
      236. Only 66% of the study group had, however, a reduction in volume to <780 cm3.
      The complication rates were similar for the two groups with regards to post
      embolisation syndrome, fibroid slough, haematoma formation, infection,
      hysterectomy and failure to embolise. Satisfaction was similar between the two
      groups, with 91% of women satisfied with the procedure. CONCLUSION: The large
      uterus does not decrease UAE's efficacy. Although 33.3% of the study group still
      had a uterus of > or =780 cm3, symptom reduction was still similar for both
      groups. Women may thus still be left with a large uterine volume but without
      symptoms. This must be taken into consideration when counselling women with an
      extremely large uterus for UAE.

PMID- 14961886
TI  - Delivering an effective outpatient service in gynaecology. A randomised
      controlled trial analysing the cost of outpatient versus daycase hysteroscopy.
AB  - OBJECTIVE: To examine the cost implications of outpatient versus daycase
      hysteroscopy to the National Health Service, the patient and their employer.
      DESIGN AND INTERVENTIONS: Randomised controlled trial. SETTING: The gynaecology
      clinic of a large teaching hospital. PARTICIPANTS: Ninety-seven women with
      abnormal uterine bleeding requiring investigation. METHODS: Women were randomly
      allocated to either outpatient or daycase hysteroscopy. They were asked to
      complete diaries recording expenses and time off work. The National Health
      Service costs were calculated for a standard outpatient and daycase hysteroscopy.
      MAIN OUTCOME MEASURES: Costs to the National Health Service, costs to the
      employer, loss of income, childcare costs and travel expenses. RESULTS: The
      outpatient group required significantly less time off work compared with the
      daycase group (0.8 days vs 3.3 days), P < 0.001. Of those women who lost income
      due to the hysteroscopy, the average loss of income was twice as much in the
      daycase group ( pound 20.40 in the outpatient group vs pound 50.60 in the daycase
      group). The average cost of childcare required to cover the time spent in
      hospital undergoing the hysteroscopy was similar in both groups, however, the
      number of women requiring childcare was small. Travel costs incurred by the women
      were 74% more in the daycase group compared with the outpatient group-with an
      average cost of pound 3.46 in the outpatient group and pound 6.02 in the daycase
      group. Daycase hysteroscopy costs the National Health Service approximately pound
      53.88 more per patient, than performing an outpatient hysteroscopy. Purchasing
      the hysteroscopes necessary to perform an outpatient hysteroscopy is a more
      expensive outlay than those required for daycase hysteroscopy. However, there are
      so many other savings that only 38 patients need to undergo outpatient
      hysteroscopy (even with a 4% failure rate) rather than daycase hysteroscopy in
      order to recoup the extra money required to set up an outpatient hysteroscopy
      service. CONCLUSION: Outpatient hysteroscopy offers many benefits over its
      traditional counterpart including faster recovery, less time away from work and
      home and cost savings to the woman and her employer and the National Health
      Service. Resources need to be made available to rapidly develop this service
      across the UK in order to better serve both patient and taxpayer.

PMID- 14961887
TI  - Duloxetine versus placebo in the treatment of European and Canadian women with
      stress urinary incontinence.
AB  - OBJECTIVE: To assess the efficacy and safety of duloxetine in women with stress
      urinary incontinence. DESIGN: Randomised double-blind, placebo-controlled
      clinical trial. SETTING: Fort-six centres in seven European countries and Canada.
      POPULATION: Four hundred and ninety-four women aged 24-83 years identified as
      having predominant symptoms of stress urinary incontinence using a clinical
      algorithm that was 100% predictive of urodynamic stress urinary incontinence in a
      subgroup of 34 women. METHODS: The case definition included a predominant symptom
      of stress urinary incontinence with a weekly incontinence episode frequency > or
      =7, the absence of predominant symptoms of urge incontinence, normal diurnal and
      nocturnal frequencies, a bladder capacity > or =400 mL and both a positive cough
      stress test and positive stress pad test. Subjects completed two urinary diaries
      prior to randomisation and three diaries during the active treatment phase of the
      study, each completed during the week prior to monthly visits. Subjects also
      completed quality of life questionnaires at each visit. Safety was assessed by
      the evaluation of treatment-emergent adverse events, discontinuation of treatment
      because of adverse events, serious adverse events, vital sign measurements,
      electrocardiograms (ECG) and clinical laboratory tests. INTERVENTION: After a two
      week placebo lead-in, women received placebo or duloxetine 40 mg BD for 12 weeks.
      MAIN OUTCOME MEASURES: The percentage decrease in incontinence episode frequency
      and the change in the Incontinence Quality of Life (I-QOL) questionnaire total
      score were prespecified as co-primary outcome variables in the protocol. RESULTS:
      Incontinence episode frequency decreased significantly with duloxetine compared
      with placebo (median decrease of 50%vs 29%; P= 0.002) with comparable
      improvements in the more severely incontinent subgroup (those experiencing at
      least 14 incontinence episodes per week at baseline; 56%vs 27% decreases; P <
      0.001). The primary analysis of I-QOL scores did not reveal a significant
      difference between treatment groups, due primarily to the carrying forward of low
      scores from patients who discontinued treatment very early due to duloxetine
      associated adverse events. The increase in I-QOL scores was significantly greater
      for duloxetine than for placebo at each of the three postrandomisation visits
      after 4, 8, and 12 weeks of treatment. Discontinuation rates for adverse events
      were higher for duloxetine (22%vs 5%; P < 0.001) with nausea being the most
      common reason for discontinuation (5.3%). Nausea tended to be mild to moderate,
      not progressive, and transient. CONCLUSIONS: The findings support duloxetine as a
      potential treatment for women with stress urinary incontinence.

PMID- 14961888
TI  - The complex relationship between smoking in pregnancy and very preterm delivery.
      Results of the Epipage study.
AB  - OBJECTIVE: To assess the relationship between cigarette smoking during pregnancy
      and very preterm births, according to the main mechanisms of preterm birth.
      DESIGN: Case-control study (the French Epipage study). SETTING: Regionally
      defined population of births in France. POPULATION: Eight hundred and sixty-four
      very preterm live-born singletons (between 27 and 32 completed weeks of
      gestation) and 567 unmatched full-term controls. METHODS: Data from the French
      Epipage study were analysed using a polytomous logistic regression model to
      control for social and demographic characteristics, pre-pregnancy body mass index
      and obstetric history. The main mechanisms of preterm delivery were classified as
      gestational hypertension, antepartum haemorrhage, premature rupture of membranes,
      spontaneous preterm labour and other miscellaneous mechanisms. MAIN OUTCOME
      MEASURES: Odds ratios for very preterm birth for low to moderate (1-9
      cigarettes/day) and heavy (>/=10 cigarettes/day) maternal smoking in pregnancy,
      estimated according to the main mechanisms leading to preterm birth. RESULTS:
      Smokers were more likely to give birth to very preterm infants than non-smokers
      [adjusted odds ratio (aOR) 1.7, 95% confidence interval (CI) 1.3-2.2]. Heavy
      smoking significantly reduced the risk of very preterm birth due to gestational
      hypertension (aOR 0.5, 95% CI 0.3-1.0), whereas both low to moderate and heavy
      smoking increased the risk of very preterm birth due to all other mechanisms (aOR
      between 1.6 and 2.8). CONCLUSION: These data from the Epipage study show that
      maternal smoking during pregnancy is a risk factor for very preterm birth. The
      impact of maternal smoking on very preterm birth appears to be complex: it lowers
      the risk of very preterm birth due to gestational hypertension, but increases the
      risk of very preterm birth due to other mechanisms. These findings might explain
      why maternal smoking is more closely related to preterm birth among multiparous
      women than among nulliparous women.

PMID- 14961889
TI  - Oxytocin mRNA content in the endometrium of non-pregnant women.
AB  - OBJECTIVE: To study oxytocin mRNA in the human endometrium at different phases of
      the menstrual cycle. DESIGN: An exploratory study in non-pregnant women. SETTING:
      The Department of Obstetrics and Gynecology, Lund University Hospital, Sweden.
      PARTICIPANTS: Thirty-three women of fertile age undergoing hysterectomy or
      endometrial curettage on routine benign gynaecologic indications. METHODS:
      Endometrial tissue was obtained throughout the menstrual cycle. The presence of
      oxytocin mRNA was investigated by in situ hybridisation and by real time PCR.
      MAIN OUTCOME MEASURES: Oxytocin mRNA signalling intensity found by in situ
      hybridisation of tissue obtained at different times of the menstrual cycle.
      Relative amounts of oxytocin mRNA measured by real time PCR. RESULTS: The signal
      for oxytocin mRNA obtained by in situ hybridisation was more pronounced in
      glandular epithelial cells than in stromal cells. Furthermore, it was most marked
      around mid-cycle. The expression of oxytocin mRNA was confirmed by real time PCR.
      CONCLUSIONS: The results indicate that oxytocin may be synthesised in the
      endometrium of non-pregnant women, particularly in the glandular epithelial
      cells. Hormone released from these sources may have a paracrine action on the
      uterus. Oxytocin mRNA expression seems to be ovarian hormone dependent with the
      highest concentration around mid-cycle.

PMID- 14961890
TI  - No association between hepatitis B or C viruses and vulval lichen planus in a UK
      population.
AB  - The aim of the study was to investigate the prevalence of hepatitis C (HCV)
      antibodies, hepatitis B surface antigen (HBsAg) carriage and liver disease in 100
      females with genital lichen planus (LP) in Oxfordshire. Sera were screened for
      HCV antibodies (AxSYM HCV 3.0 Abbott), HBV surface antigen (AxSYM HBsAg V2
      Abbott), mitochrondrial and anti-smooth muscle antibodies. Liver function tests
      were undertaken. All sera were negative for HCV antibody and HBsAg. Transiently
      abnormal liver function tests (2) and liver specific antibodies (2) were detected
      in four patients with no underlying liver disease. We found no association
      between HBV or HCV and genital LP in this population.

PMID- 14961891
TI  - Evans syndrome and pregnancy: a case report.

PMID- 14961892
TI  - The use of McCartney tube during total laparoscopic hysterectomy for gender
      reassignment: a report of two cases.

PMID- 14961893
TI  - Partial ischemic necrosis of the uterus following a uterine brace compression
      suture.

PMID- 14961894
TI  - Non-surgical management of a mid-trimester abdominal pregnancy.

PMID- 14961895
TI  - Prolonged treatment of massive postpartum haemorrhage with recombinant factor
      VIIa: case report and review of the literature.

PMID- 14961896
TI  - Individualising use of aspirin to prevent pre-eclampsia: a framework for clinical
      decision making.

PMID- 14961897
TI  - A systematic review of training in acute obstetric emergencies.

PMID- 14961900
TI  - Squamous cell carcinoma in situ of the skin: history, presentation, biology and
      treatment.
AB  - Squamous cell carcinoma in situ (SCCIS) of the skin is a problem commonly dealt
      with by dermatologists. The classic presentation, originally described by Bowen,
      is easily recognized, but presentation on some anatomical surfaces may be
      associated with less than typical features. Major aetiological factors for this
      disease are UV light, human papillomavirus infection and immunosuppression. The
      natural course of SCCIS is usually prolonged, with treatment being appropriate,
      but not urgent. The choice of therapy requires consideration of the location of
      the lesion, and a desire for a high cure rate without causing loss of form,
      function or cosmesis. The immunomodulatory agent imiquimod has offered a
      significant advance for the topical treatment of SCCIS. Our improved
      understanding of the underlying biology of SCCIS permits us to make rational
      choices of treatment. In the future we may be able to determine which of these
      lesions may progress to invasive disease, and help us select the most effective
      therapy.

PMID- 14961902
TI  - Circulating basement membrane zone antibodies are found in lichen sclerosus of
      the vulva.
AB  - This study was undertaken to investigate the prevalence of basement membrane zone
      (BMZ) antibodies, their subtypes and clinical correlations in 96 patients
      attending the Oxford vulval clinic with lichen sclerosus (LS) of the vulva.
      Indirect immunofluorescence of serum (intact and split skin) to immunoglobulin
      (Ig)G was performed looking for the presence or absence of staining at the BMZ.
      Eighteen patients' sera (14 with positive indirect immunofluorescence to IgG)
      were examined for IgG antibodies of subclasses IgG1, 2 and 3, and 23 sera were
      examined for IgG4 subclass. Immunoblotting was performed in seven patients, and
      showed antibodies to BP180 in six patients and BP230 in one. One-third of
      patients with vulval LS had BMZ antibodies binding to the epidermal side of salt
      split skin. Immunoblotting showed antibodies to BP180 collagen XVII (six of seven
      patients) and BP230 in one. The subclasses were chiefly IgG1 and 2, different
      from those seen in bullous pemphigoid. No clinical correlation was found between
      the presence of antibodies and the presence of erosions, severity of scarring,
      age of onset of disease or response to treatment. These antibodies may be a
      reflection of a tendency to produce autoantibodies or be relevant to
      pathogenesis.

PMID- 14961903
TI  - Morbidity and cost of atopic eczema in Australia.
AB  - The severity, morbidity and financial costs of atopic eczema (AE) were assessed
      during a 1-year prospective study of a cohort of 85 people aged 14-63 years (mean
      36 years) with the disease. A dermatologist examined each participant using the
      Six Area Six Sign Atopic Dermatitis severity scoring system to classify severity.
      Participants completed a Dermatology Life Quality Index (DLQI), a Nottingham
      Eczema Severity Score (NESS) and an ongoing diary of health-care consultations
      and treatment costs. Follow up by mail to each participant was conducted every 2
      months and participants completed a NESS, a DLQI and a diary of costs incurred.
      The DLQI data revealed that 36% spent over 10 min per day applying treatments,
      28% indicated that AE influenced the clothes they wore, 21% felt embarrassed by
      their skin and 15% reported problems with treatments. There appeared to be a
      relationship between increased morbidity and increased severity. The average
      annual out-of-pocket cost for products used for treatment was A$425, ranging from
      A$13.50 to over A$2000 per individual. The average out-of-pocket cost for medical
      consultations was A$120, ranging from zero to over A$800 per individual. Although
      there were concerns about the reproducibility of the severity and morbidity
      measures, the data showed that AE can have substantial effects both financially
      and from a personal perspective for those affected.

PMID- 14961904
TI  - Retrospective review of teledermatology in the Waikato, 1997-2002.
AB  - We reviewed scheduled interactive teledermatology consultations from 1997 to 2002
      between the Department of Dermatology of Health Waikato in Hamilton and remote
      sites at Taumarunui Hospital, Taupo Health Centre and the Ranolf Medical Centre,
      Rotorua, in New Zealand. Eighty-five per cent of 384 appointments were attended
      and most non-attendances were unexplained. The reason for consulting a
      dermatologist was inflammatory skin disease in 74% of cases, cutaneous infection
      in 10%, a skin lesion in 12% and no diagnosis was made in 4%. Follow ups were
      arranged for 41%, mainly by telemedicine (74%). Despite the apparent success of
      75% of consultations and positive feedback from patients attending them, the
      service has not proved sustainable long-term. This is because of other priorities
      for the delivery of health care, lack of support by clinicians and
      administrators, and ongoing financial costs.

PMID- 14961905
TI  - Dermatofibrosarcoma protuberans: a clinicopathological analysis of 10 cases in
      Asians.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive cutaneous neoplasm
      that exhibits a marked tendency for recurrence after local excision. This case
      series aims to study the clinical, histological and immunohistochemical features
      of DFSP in Asians. Ten patients with DFSP diagnosed between 1992 and 2001 were
      reviewed. There were more women than men in a ratio of 4:1. There were six
      Chinese, two Malays, one Indian and one Eurasian. The mean age was 38 years. The
      duration of each lesion before excision varied from 6 months to 27 years. Fifty
      per cent of tumours occurred on the trunk. On histology, all the lesions were
      dermal-centred spindle cell tumours, extending to the subcutis, and exhibited the
      characteristic storiform pattern. One tumour also demonstrated fibrosarcomatous
      changes. Two tumours were of the rare pigmented variant (Bednar tumour).
      Immunohistochemistry with CD34 was positive in all cases, except the
      fibrosarcomatous area of one tumour, which was negative for CD34. For comparison,
      six cases of deep-penetrating dermatofibroma were stained for CD34 and all showed
      an absence of CD34 expression. Wide excision of the tumour was performed in all
      cases of DFSP. There was no recurrence after mean follow up of 6 years (range
      2.25-9.5 years).

PMID- 14961906
TI  - Treatment of primary cutaneous follicular centre lymphoma with rituximab: a
      report of two cases.
AB  - Rituximab (anti-CD20 chimeric monoclonal antibody) has been demonstrated to have
      significant activity in nodal B-cell lymphomas, with very few associated adverse
      effects. Although primary cutaneous B-cell lymphomas (PCBCL) also express the
      CD20 antigen, relatively few reports of rituximab use in PCBCL have been
      published to date. We present two cases of primary cutaneous follicular centre
      lymphoma treated with rituximab (375 mg/m(2)/week intravenously for 4 weeks).
      Both cases responded to rituximab, with one partial response and one complete
      response seen. No adverse effects were observed. To date, disease progression has
      occurred in one case during overall follow up at 6 and 17 months. The potential
      role of rituximab in the treatment of these lymphomas is discussed.

PMID- 14961907
TI  - Metastatic Merkel cell carcinoma to the soft tissues of the lower back.
AB  - Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine carcinoma.
      It has a propensity for both locoregional and distant recurrence despite
      treatment. We describe the case of a 51-year-old man diagnosed with MCC of the
      left forehead. At 14 months post surgery and adjuvant radiotherapy he developed
      an isolated deposit of metastatic MCC in the paraspinal soft tissues of his lower
      back. This atypical site of metastatic disease was treated with radiotherapy and
      combination chemotherapy. Atypical and isolated sites of metastatic MCC, although
      infrequently reported, highlight the often bizarre nature of this aggressive skin
      cancer. Treatment in such cases needs to be individualized.

PMID- 14961908
TI  - Granulomatous mycosis fungoides with extensive chest wall involvement.
AB  - A 40-year-old woman presented with a 5-year history of a mass overlying her right
      pectoralis major muscle. Histopathology of the lesion revealed a florid
      granulomatous infiltrate including an atypical lymphocytic component with marked
      epidermotropism consistent with granulomatous mycosis fungoides. Staging
      investigations demonstrated the tumour to be localized to the right chest.
      Consequently, the patient was treated with radiotherapy (50 Gy) to the lesion
      with good clinical effect. However, she soon developed a clinically palpable
      lesion on the left chest outside the radiotherapy field. Positron emission
      tomography scanning demonstrated an extensive left-sided chest wall tumour and
      also residual tumour on the right. This left-sided lesion failed to respond to
      systemic chemotherapy. Further radiotherapy (50 Gy) has recently been
      administered to the left chest lesion; the response is being monitored. While
      granulomatous inflammation has been previously described in cutaneous T-cell
      lymphomas, it is rare and is often associated with a delay in the diagnosis and
      difficulty with clinical staging. The clinical presentation can be extremely
      variable and consequently, diagnosis rests with histological features,
      immunohistochemical studies and gene rearrangement analysis.

PMID- 14961909
TI  - Psoriasis induced by topical imiquimod.
AB  - We report the provocation of localized psoriasis at the sites of application of
      topical imiquimod, possibly evolving into a generalized flare. A patient with pre
      existing psoriasis that had been stable for 14 years was treated with imiquimod
      5% cream daily for 6 weeks to three superficial basal cell carcinomas. During
      treatment one of the lesions developed severe local skin reactions necessitating
      rest periods, and received only 18 applications in 6 weeks. The other two lesions
      were treated for all 42 days. Psoriasiform changes developed at all three
      application sites. Nine-and-a-half weeks after completing treatment the patient
      developed disseminated small psoriatic lesions. Other recognized triggers of
      psoriasis were not identified. The psoriasis resolved slowly with conventional
      treatment.

PMID- 14961910
TI  - Granulomas in common variable immunodeficiency: a diagnostic dilemma.
AB  - A 60-year-old man with common variable immunodeficiency presented with a 7-year
      history of violaceous plaques and papules on the thighs, arms and trunk. In the
      preceding 2 years he had developed new lesions on both hands. He had been
      previously diagnosed with sarcoidosis on the basis of skin and visceral
      histology, but subsequent opinion was that these were sarcoid-like granulomas
      rather than being representative of true sarcoidosis. Biopsy of the hand lesions
      showed necrotizing granulomas, and a single acid-fast bacillus (AFB) was
      identified on Wade-Fite stain. Subsequent repeat tissue biopsies for histology,
      culture and polymerase chain reaction testing failed to confirm the presence of
      mycobacterial organisms and it was felt that the organism was a contaminant
      introduced during tissue processing. The hand lesions responded well to
      intralesional injections of triamcinolone acetonide 10 mg/mL and oral
      tetracycline 500 mg b.d. was later introduced with a good clinical response. The
      diagnostic dilemma of finding granulomatous inflammation in a patient with common
      variable immunodeficiency, and the significance of a single AFB on histology are
      discussed. The treatment of sarcoid-like granulomas with tetracycline therapy is
      also commented on.

PMID- 14961911
TI  - Inverted follicular keratosis simulating malignant melanoma.
AB  - A 93-year-old woman was noted to have a single pigmented lesion on the posterior
      aspect of her neck. Clinical examination revealed a 12 x 8-mm flat lesion, with
      an irregular border and variegated pigmentation. Dermatoscopic examination
      revealed a lesion with multiple colours, featureless areas and black dots,
      suggestive of malignant melanoma. With a presumed clinical diagnosis of malignant
      melanoma, an elliptical excision was performed, with a 1-cm margin. However,
      histological examination revealed the unexpected diagnosis of pigmented inverted
      follicular keratosis.

PMID- 14961912
TI  - Periodic painful purpura: fact or factitious?
AB  - A 60-year-old woman with multiple psychosocial issues presented with a history of
      spontaneous painful bruising on her left upper arm. Extensive investigations did
      not reveal any abnormality apart from an elevated activated partial
      thromboplastin time as a result of factor XII deficiency. An autoerythrocyte
      sensitization test reproduced the tender bruises on her back. Our patient
      reported relief of pain with promethazine injections. She was subsequently
      referred to the psychiatric team for ongoing assessment and management. Having an
      awareness of this rare condition will assist in the prevention of unnecessary
      investigation of such cases and will allow the early referral of patients for
      appropriate psychological counselling.

PMID- 14961913
TI  - Allergic contact dermatitis caused by the clothing dye, disperse blue 106, an
      important contact allergen that may be frequently missed.
AB  - A 43-year-old woman presented with a history of dermatitis in a somewhat linear
      pattern under her breasts, across her back and around her waist. This dermatitis
      occurred after wearing a new blue dress with a blue lining. Patch testing showed
      an allergy to disperse blue 106 dye and also to her dress lining. However, she
      was not positive to p-phenylene-diamine, a dye in the standard patch test series.
      We recommend that any patient even slightly suspected of having an allergy to a
      textile dye should be tested with disperse blue, in addition to the standard
      series.

PMID- 14961914
TI  - Generalized essential telangiectasia.
AB  - A 43-year-old woman presented with a 1-year history of telangiectatic lesions on
      her lower legs. The lesions progressively spread to involve her thighs and left
      arm. She had no family or personal history of recurrent haemorrhage or
      telangiectases. Her general health was unaffected. The diagnosis of generalized
      essential telangiectasia was made on the basis of clinical presentation and
      investigations. Generalized essential telangiectasia is a rare condition that can
      only be diagnosed if other primary and secondary telangiectasias are excluded. It
      is probably under-reported, with patients mistakenly diagnosed with atypical
      hereditary haemorrhagic telangiectasia.

PMID- 14961915
TI  - Granular cell basal cell carcinoma.
AB  - A 69-year-old woman presented with a 2-year history of a slowly growing tumour on
      the nose. The clinical diagnosis was basal cell carcinoma (BCC) and a complete
      excision was performed. Histologically, the tumour had the general features of a
      BCC but with sheets and nests of cells with granular cytoplasmic changes in the
      centre of the lesion. A pathological diagnosis of granular cell BCC was made. On
      immunohistochemical examination, the tumour cells were Ber-EP4, cytokeratin
      AE1/AE3 and cytokeratin CAM 5.2 positive but S100 protein negative. Only the
      granular cells were CD68 antigen (monoclonal antibody KP1) positive.

PMID- 14961916
TI  - Severe contact dermatitis as a result of an antiseptic bath oil.
AB  - Siblings aged 7 and 5 years developed extensive truncal and flexural inflammation
      and desquamation unresponsive to standard eczema therapy. After delays in
      diagnosis, subsequent history revealed prior use of an antiseptic bath oil in a
      much stronger concentration than recommended. The case illustrates the severe
      irritant contact dermatitis that can arise following inadequate dilution of
      antiseptic bath oils, presumably as a result of skin contact with benzalkonium
      chloride and triclosan. Features that may direct attention to such irritant
      dermatitis are flexural predominance with superficial desquamation and rapid
      improvement after avoidance of exposure to the antiseptic solution.

PMID- 14961917
TI  - Basal cell carcinoma developing in an influenza vaccine scar.

PMID- 14961918
TI  - Exacerbation of amyopathic dermatomyositis in Orientals: a high alert for
      nasopharyngeal carcinoma.

PMID- 14961919
TI  - Acquired reactive perforating collagenosis associated with myelodysplastic
      syndrome evolving to acute myelogenous leukaemia.

PMID- 14961925
TI  - Longitudinal designs, methods and analysis in psychiatric research.
AB  - OBJECTIVE: To outline the strengths and limitations of longitudinal research
      designs in psychiatry, and to describe different types of longitudinal designs
      and methods for analyzing longitudinal data. METHOD: Key references on
      longitudinal methods were reviewed and examples drawn from literature in
      psychiatry and psychology. RESULTS: Longitudinal studies provide important
      information regarding the incidence and developmental trajectories of mental
      disorders. They allow for identification of risk factors and developmental
      concomitants. Recent developments in statistical methods for analyzing
      longitudinal data provide efficient estimates of change and predictors of change
      over time, identification and characteristics of distinct subgroups defined by
      change pattern, and improved methods for obtaining unbiased population estimates
      when data are incomplete. CONCLUSION: Longitudinal designs, methods and analysis
      can contribute to psychiatric studies on risk factors for common mental
      disorders, studies of early intervention and prevention and treatment outcomes.

PMID- 14961926
TI  - Australian psychiatrists today: proud of their profession but stressed and
      apprehensive about the future.
AB  - OBJECTIVE: To examine the levels of satisfaction and stress of Australian
      psychiatrists. METHOD: A survey was mailed in December 2002 to all Fellows of the
      Royal Australian and New Zealand College of Psychiatrists residing in Australia;
      1039 out of 2059 (50%) returned the questionnaire. RESULTS: The large majority of
      respondents (79%) were proud of being a psychiatrist. Most (88%) reported being
      satisfied with their work. Reasons for dissatisfaction varied between public and
      private psychiatrists. Private psychiatrists nominated litigation/indemnity
      issues as the most frequent (69%) while the most common for public psychiatrists
      was lack of beds (47%). The main reason for satisfaction was helping patients get
      better (72%). Sixty-two percent found their work in the previous 12 months to be
      stressful. Dissatisfied psychiatrists were 11 times as likely to report being
      stressed as those satisfied. In the previous 12 months, 34% reported having had a
      threat of legal action, 39% had to answer a formal complaint, 67% had been
      verbally or physically abused by patients or relatives and 29% had patients who
      had suicided. Overall, psychiatrists were more pessimistic about the future than
      optimistic and 15% said they would not do psychiatry again. There were few
      differences according to state of origin or type of practice. However, females
      differed from males in several areas. CONCLUSION: Helping patients was reported
      as the main source of satisfaction for Australian psychiatrists while not being
      able to provide the best care for patients was described as one of the main
      reasons for dissatisfaction. Although most Australian psychiatrists are satisfied
      and proud of their profession, they are stressed and often experience verbal or
      physical abuse and threats of legal action and complaints. They are apprehensive
      about the future. The increasing number of females in the profession, their
      higher levels of stress and dissatisfaction, and other differences from males
      must be taken into account as the profession reshapes its future. There is a need
      for regular surveys of this kind.

PMID- 14961927
TI  - The debate continues: unique ethics for psychiatry.

PMID- 14961929
TI  - Generic versus specialist clinical work roles of occupational therapists and
      social workers in mental health.
AB  - OBJECTIVE: There has been limited research in Australia examining the extent of
      generic and specialist work activities carried out by occupational therapists and
      social workers since the introduction of mental health reform. The aim of the
      project was to: (i) identify specific clinical work activities of occupational
      therapists and social workers; and (ii) identify whether they are performing a
      greater proportion of generic than specialist clinical or discipline specific
      core skills. METHOD: A cross-sectional survey of 304 (response rate 76.6%)
      occupational therapists and social workers working in mental health was
      conducted. For the purposes of the study a new instrument was developed to cover
      broad categories of clinical work activities. RESULTS: The majority of the
      respondents were female, under the age of 30 years, who had worked in their
      current position less than 5 years. Generic work activities were the primary
      activities of the two professional groups, with nine of the 10 activities
      undertaken most frequently being generic in nature. Social work respondents
      performed more work activities while occupational therapists undertook more
      specialist clinical activities. CONCLUSIONS: Occupational therapists and social
      workers are required to have common competencies in addition to discipline
      specific competencies in order to undertake broad-spectrum mental health service
      activities. This has implications for the skill mix, education and training and
      recruitment of staff.

PMID- 14961930
TI  - Improving collaboration between private psychiatrists, the public mental health
      sector and general practitioners: evaluation of the Partnership Project.
AB  - OBJECTIVES: We describe the evaluation of the Partnership Project, which was
      designed to improve linkages between public and private sector mental health
      services. We consider the Project's key elements: a Linkage Unit, designed to
      improve collaborative arrangements for consumers and promote systems-level and
      cultural change; and the expansion of private psychiatrists' roles to include
      supervision and training, case conferencing and secondary consultation. The
      evaluation aimed to describe the impacts and outcomes of these elements. METHOD:
      The evaluation used de-identified data from the Linkage Unit database, the
      Project's billing system, and the Health Insurance Commission (HIC). It drew on
      consultations with key stakeholders (semistructured interviews with 36 key
      informants, and information from a forum attended by over 40 carers and a meeting
      of five public sector and three private sector psychiatrists) and a series of
      case studies. RESULTS: The Linkage Unit facilitated 224 episodes of collaborative
      care, many of which had positive outcomes for providers, consumers and carers. It
      had a significant impact at a systems level, raising consciousness about
      collaboration and influencing procedural changes. Thirty-two private
      psychiatrists consented to undertaking expanded roles, and the Project was billed
      $78 032 accordingly. Supervision and training were most common, involving 16
      psychiatrists and accounting for approximately 80% of the total hours and cost.
      Commonwealth expenditure on private psychiatrists' participation in the expanded
      roles was not associated with a reduction in benefits paid by the HIC. Key
      informants were generally positive about the expanded roles. CONCLUSIONS: The
      Project represented a considered, innovative approach to dealing with poor
      collaboration between the public mental health sector, private psychiatrists and
      GPs. The Linkage Unit achieved significant systems-level and cultural change,
      which has the potential to be sustained. Expanded roles for private
      psychiatrists, particularly supervision and training, may improve collaboration,
      and warrant further exploration in terms of costs and benefits.

PMID- 14961931
TI  - The neurobiology of bipolar disorder: findings using human postmortem central
      nervous system tissue.
AB  - OBJECTIVE: Postmortem brain studies have been undertaken to understand changes in
      the molecular architecture of the central nervous system (CNS) of subjects with
      bipolar disorder. These studies, along with a limited number of functional
      neuroimaging studies, have been reviewed to provide information on the
      neurobiology underlying the disorder. METHOD: Findings from the study of
      postmortem brain tissue and neuroimaging were reviewed if their focus was on the
      molecular architecture of the human CNS to identify future lines of research
      required to understand the underlying pathology of bipolar disorder. RESULTS:
      There is considerable evidence to implicate the serotonergic system of the CNS
      and abnormalities in signal transduction pathways in the pathology of bipolar
      disorder. In addition, preliminary findings suggest that changes in the
      benzodiazepine binding site on the gamma aminobutyric acidA receptor may be
      affected in bipolar disorder. CONCLUSIONS: Further systematic studies on the
      serotonergic systems of the CNS, as well as the interaction between
      neurotransmitter receptors, G-proteins and signal transduction pathways are
      required to better understand the pathology of bipolar disorder. In addition,
      findings on the serotonin transporter indicate that changes in presynaptic
      function may be a critical component of the pathology of bipolar disorder.

PMID- 14961932
TI  - Some recommendations to assess depression in Chinese people in Australasia.
AB  - OBJECTIVE: To provide some general recommendations for psychiatric assessment of
      depression among Chinese patients within a predominately Western society. METHOD:
      A literature review is provided with interpretive comments. RESULTS: The
      prevalence of depression reported in community studies undertaken in Chinese
      communities is very low. To what extent Chinese people experience and seek help
      for depression, and how they report depressive symptoms have long been topics of
      some importance. The impact of acculturation as well as concepts and
      interpretations of illness in traditional Chinese medicine are discussed.
      Awareness of sensitive issues and practices within the Chinese culture will
      facilitate communication between medical professionals and patients, resulting in
      more accurate identification and diagnosis of depressive disorders. CONCLUSION:
      Direct but culturally sensitive and empathic questioning of psychological
      symptoms is needed to unveil patients' explanatory models, as most Chinese
      initially nominate only somatic symptoms to health practitioners. Successfully
      treated patients can promote earlier and wider utilization of mental health
      services to other Chinese people.

PMID- 14961933
TI  - Correlates of firesetting in a community sample of young adolescents.
AB  - OBJECTIVE: To investigate relationships between firesetting, antisocial
      behaviour, individual, family and parenting factors in a large community sample
      of adolescents. METHOD: A cross-sectional study of students (n = 2596) aged 13
      years on average, from 27 schools in South Australia with a questionnaire on
      firesetting, antisocial behaviour (adapted 21-item Self Report Delinquency
      Scale), risk-taking, drug use, suicidality, physical and sexual abuse, depressive
      symptomatology, hopelessness, anxiety, locus of control, self-esteem, family
      functioning (McMaster Family Assessment Device) and parenting style (Influential
      Relationships Questionnaire). Data analysis included chi2, anova and logistic
      regression. RESULTS: Large significant differences are found between firesetters
      and non-firesetters on all measures. Among adolescents with serious levels of
      antisocial behaviour (7+ acts included in diagnostic guidelines for DSM-IV
      conduct disorder), firesetters differ from non-firesetters in reporting more
      extreme antisocial behaviour (10+ acts), extreme drug use, suicidal behaviour,
      and perceived failure at school. Gender differences are apparent. A study
      limitation is the single item assessment of firesetting. CONCLUSIONS: Self-report
      firesetting is strongly associated with extreme antisocial behaviour in young
      community adolescents, in support of existing evidence from incarcerated
      delinquent and psychiatric populations. Early detection of community firesetters
      demands further assessment and intervention. Clinicians should consider its
      coexistence with serious drug use and high risk-taking (especially in girls), and
      suicidality, sexual and physical abuse (in boys).

PMID- 14961934
TI  - Understanding the relationships between wellbeing, goal-setting and depression in
      children.
AB  - OBJECTIVES: This study investigates children's conceptions of happiness and
      wellbeing in relation to goal choice. It examines the prevalence and impact of
      Conditional goal setting (CGS) on levels of wellbeing and depression. Conditional
      goal setting describes commitment toward an important goal resulting from a
      conception that happiness is an end-point achieved through the attainment of this
      goal. Conditional goal setting has been identified as a significant factor in the
      development and maintenance of depression in adults. This study examines these
      same concepts among children. METHOD: Combined interpretative and quantitative
      methodology is used. Thirty-six children aged 10-12 years participated in six
      focus groups discussing their understandings of happiness, important goals and
      beliefs concerning CGS. Children each attended one of three primary schools in
      the Perth metropolitan district. They also completed CGS and depression
      questionnaires. RESULTS: Responses were categorized into a number of common
      themes. Response content and the number of responses in each theoretical area
      were identified and discussed. The majority of participants conceptualized
      happiness as a goal dependent upon something extrinsic to themselves (such as an
      achievement or event). Statistical analyses suggested a significant relationship
      between goal setting styles, conceptualizations of happiness and depression.
      Depressed children were more likely than non-depressed children to be conditional
      goal setters. CONCLUSIONS: Findings suggest that some children conceptualize
      happiness as an outcome that is dependent on their important achievements and
      acquisitions. This conceptualization is related to depression. Alternatively, non
      depressed children tended to conceptualize happiness as a process independent of
      goal achievement or failure.

PMID- 14961935
TI  - Psychiatric disorders in homeless men and women in inner Sydney.
AB  - OBJECTIVE: To determine the 12-month prevalence of mental disorders among
      homeless people in inner Sydney and compare this data with data collected on
      homeless populations in other Western cities. METHOD: Representative sample of
      210 homeless men and women in Sydney were interviewed using the Composite
      International Diagnostic Interview (2.0). RESULTS: Seventy-three percent of men
      and 81% of women met criteria for at least one mental disorder in the past year
      and 40% of the men and 50% of the women had at least two mental disorders. The
      prevalence rate of schizophrenia among men and women was 23% and 46%,
      respectively. There was considerable comorbidity between mental disorders with
      one in five men (20%) and 29% of women meeting criteria for two mental disorders.
      The prevalence of any mental disorder is four times higher among homeless men and
      women in inner Sydney than within the Australian general population.
      International comparisons demonstrated significant cross-cultural differences in
      the prevalence of mental disorders among the homeless. CONCLUSIONS: This paper
      highlights the need for comparable epidemiological data when examining an
      international problem such as homelessness.

PMID- 14961936
TI  - Insight and hopelessness in forensic patients with schizophrenia.
AB  - OBJECTIVE: To quantitatively explore the level of insight in forensic patients
      with schizophrenia, and its relationship to symptoms and to a history of
      violence. In addition, to test the hypothesis that scores in the insight domains
      of 'compliance' and 'awareness of illness' are positively correlated with scores
      on a self-report scale measuring 'hopelessness'. METHOD: The study consisted of a
      cross-sectional survey. Subjects were inpatients and outpatients in the
      rehabilitation service of the Victorian Institute of Forensic Mental Health.
      Twenty-eight patients with a diagnosis of schizophrenia and a history of serious
      offending consented to take part. Twenty-two of these had committed homicide.
      Measures were obtained for each on the Schedule for Assessment of Insight, the
      Positive and Negative Syndrome Scale for Schizophrenia and the Beck Hopelessness
      Scale. RESULTS: The mean insight score for forensic patients was 8.39 (SD 4.88).
      Insight scores did not differ significantly between those subjects who had a
      history of violence prior to their index offence and those who did not. Awareness
      of illness, but not compliance, was positively correlated with level of
      hopelessness. A higher level of awareness of having a mental illness was thus
      related to feeling more hopeless about the future. CONCLUSIONS: Mean insight
      scores in patients with schizophrenia with a forensic history do not differ
      significantly from those in non-forensic populations. Being more aware of being
      mentally ill may be a risk factor for hopelessness about the future. The
      limitations of the study are the small sample size, and the fact that it is
      confined to a relatively clinically stable population.

PMID- 14961937
TI  - Spasmodic dysphonia, a rare form of tardive dystonia, induced by low-dose
      risperidone?

PMID- 14961938
TI  - Mental illness and employment status.

PMID- 14961939
TI  - Risperidone-induced long-term weight gain in a patient with schizophrenia.

PMID- 14961940
TI  - Refractory pain-depression syndrome treated with tianeptine: a case report.

PMID- 14961946
TI  - Artificial organs for bridge to therapy.

PMID- 14961947
TI  - Mechanical circulatory support and the genomics revolution?

PMID- 14961949
TI  - The evolving concept of "Artificial Organs" and the emerging Canadian strategy.

PMID- 14961950
TI  - One defining moment in an altered future.

PMID- 14961951
TI  - Ventricular assist devices as a bridge to cardiac transplantation: the Ottawa
      experience.
AB  - This article reports our experience with ventricular assist devices (VADs) as a
      bridge to cardiac transplantation. From 1991 to 2003, a total of 42 patients
      received a Thoratec VAD (Thoratec Laboratories Corporation Inc., Pleasanton, CA,
      U.S.A.) (Group T) and 12 patients received a Novacor VAD (WorldHeart Corporation,
      Ottawa, Canada) (Group N). Thirty Thoratec patients were transplanted compared to
      six in the Novacor group. Four more Novacor patients are still supported. Of the
      transplanted patients, 87% survived to hospital discharge in Group T and 67% in
      Group N. Infections affected 29% and 50% of Group T patients during support and
      post-transplantation, respectively, compared to 25% and 0%, respectively, in
      Group N. Neurologic complications affected 33% of patients in each group during
      support. Reopening rates for bleeding during support were 45% and 42% in Groups T
      and N, respectively. There were no significant differences in outcomes between
      the two groups. Our study demonstrated the effectiveness of VADs in bridging
      mortally ill cardiac patients to successful heart transplantation.

PMID- 14961952
TI  - Bone marrow cells in the repair and modulation of heart and blood vessels:
      emerging opportunities in native and engineered tissue and biomechanical
      materials.
AB  - Adult bone marrow-derived stem/progenitor cells have traditionally been
      considered to be tissue-specific cells with limited capacity for differentiation.
      However, recent discoveries have generated tremendous excitement regarding
      possible applications of stem cells, particularly bone marrow-derived stem cells,
      in the treatment of human diseases. The potential ability to regenerate cells of
      various different lineages has raised the therapeutic possibility of using these
      bone marrow-derived stem cells as a source of cells for tissue repair and
      regeneration. Tissue engineering is a rapidly expanding interdisciplinary field
      aimed at restoring function to tissues through the delivery of constructs which
      become integrated into the patient. The use of bone marrow-derived stem cells
      provides a less invasive source for cells applicable to tissue engineering,
      including cardiovascular tissues such as heart valves, blood vessels, and
      myocardium. Although these strategies are in the early stages of development,
      they are conceptually promising and offer important insights into the future
      treatment of various cardiovascular ailments.

PMID- 14961953
TI  - Patient selection for left ventricular assist devices.
AB  - The use of mechanical support as a bridge to cardiac transplant has become the
      standard of care in many cardiac transplant centers. This therapy has been shown
      to increase survival and improve morbidity in carefully selected patients waiting
      for heart transplantation. With approximately 30000 patients being listed
      worldwide for transplant every year and only 3500 transplantations performed
      annually, alternative strategies need to be developed to minimize morbidity and
      mortality in this high-risk population. Patient selection remains the primary
      determinant of success with left ventricular assist device (LVAD) therapy. This
      article will review both the cardiac and extracardiac considerations needed in
      the assessment of patient suitability for LVAD support as a bridge to
      transplantation.

PMID- 14961954
TI  - Left ventricular unloading in a patient with end-stage cardiomyopathy and
      medically unresponsive pulmonary hypertension.
AB  - Severe, medically unresponsive pulmonary hypertension (PHT) is considered to be a
      contraindication for orthotopic heart transplantation (OHT). Chronic left
      ventricular (LV) unloading using a left ventricular assist device (LVAD) might
      result in reversal of the elevated pulmonary vascular resistance (PVR), allowing
      successful OHT in such patients. In this study, we present a patient with end
      stage ischemic cardiomyopathy and fixed, elevated PVR (7.1 Wood units) who
      underwent implantation of a Novacor LVAD (Baxter Healthcare Corp., Deerfield, IL,
      U.S.A.), with a subsequent reduction in PVR to 1.2 Wood units and successful OHT
      eleven months post-LVAD implantation. Three years after heart transplant, the
      patient still leads an active life with no right heart failure. In conclusion,
      OHT is not contraindicated in patients with end-stage heart failure and medically
      unresponsive PHT in the presence of elevated left atrial pressure. Left
      ventricular unloading should be considered in these patients to allow reversal of
      the elevated PVR before OHT.

PMID- 14961955
TI  - Improved early survival with the total artificial heart.
AB  - We report our experience with the total artificial heart (TAH) to determine if
      outcomes have improved. Thirty-one patients received the TAH as a bridge to
      transplant and were divided into the two groups A (eighteen implanted in the
      first eight years) and B (thirteen implanted in the last eight years). Changes in
      management included immediate sternal closure, early extubation, delayed
      transplant listing, early rehabilitation, and measurement of preformed
      antibodies. The infection rate in B was lower than in A, both during support (31%
      versus 39%) and following transplant (38% versus 72%), and rejection was lower in
      B than in A (0% versus 44%). There was no difference in neurological events
      between groups; however, reopening was more frequent in B (61% versus 28%).
      Hospital survival increased from 61% in A to 85% in B; however, this was not
      statistically significant. We hypothesize that this improvement was likely due to
      changes in patient management.

PMID- 14961956
TI  - Heart transplantation at the Ottawa heart institute: comparison with Canadian and
      international results.
AB  - Heart transplantation has been carried out in 340 patients in Ottawa, including
      seventy-one who required mechanical circulatory support as a bridge to
      transplant. Survival in Ottawa was compared with other Canadian centers based on
      data from the Canadian Organ Replacement Register up to the year 2000 and with
      the International Society of Heart and Lung Transplantation (ISHLT) registry
      2001. For survival analysis, the number of adult patients at risk at year 0 was
      303 (87 transplanted from 1985 to 1990, 105 from 1990 to 1994, and 111 from 1995
      to 2000). The Statistical Analysis System (SAS) life test procedure was used.
      Survival was not adjusted for comorbidities or heart failure class. For the year
      of transplant 1985-1989, one-, five-, and ten-year patient survival in Ottawa was
      83%, 70%, and 60%, respectively, compared to 82%, 71%, and 54%, respectively, for
      Canada (Wilcoxon test, P = 0.71), and compared to one- and five-year survival for
      ISHLT from 1980 to 1987 at 76% and 60%, respectively. For 1990-1994, one-, five-,
      and ten-year patient survival in Ottawa was 88%, 81%, and 74%, respectively,
      compared to 80%, 71%, and 61%, respectively, for Canada (P = 0.05), and compared
      to one- and five-year survival for ISHLT from 1998 to 1992 at 80% and 68%,
      respectively. For 1995-2000, one- and five-year patient survival in Ottawa was
      90% and 82%, respectively, compared to 85% and 76%, respectively, for Canada (P =
      0.09), and compared to one- and five-year survival for ISHLT from 1993 to 1996 at
      82% and 68%, respectively. Survival after heart transplantation in Ottawa
      compares favorably with Canadian and international data.

PMID- 14961957
TI  - Therapeutic left ventricular assist device and apheresis on dilated
      cardiomyopathy.
AB  - Pathogenesis and therapies of dilated cardiomyopathy (DCM) have been discussed
      for a long time, but both of the ultimate answers are still unknown. In the last
      decade, the pathogenic role of immunological factors, such as cardiac autoimmune
      antibodies and cytokines, have been discussed attentively. This has led to one
      possible new therapy, immunoadsorption, which removes antibodies, and it has made
      a remarkable effect. However, there are other factors to remove. For the removal
      of cytokines and neurohormones, the most effective method is hemofiltration (HF).
      Also, double-filtration plasmapheresis (DFPP) removes immunoglobulin as well as
      low-density lipoprotein (LDL) and coagulation factors that may improve blood
      circulation, including the coronary arteries. Therefore, to eliminate all
      deteriorative factors, both apheresis therapies, HF and DFPP, should be
      performed. Due to the shortage of donor hearts, left ventricular assist systems
      (LVAD) have been used as a bridge to transplantation. It has now been reported
      that the total unloading of the left ventricle does not only maintain, but also
      recovers, the cardiac function, even from end-stage heart failure. However, the
      patients who have obtained a long-lasting recovery of cardiac function from an
      LVAD are still in a minority. To make this the majority, therapeutic LVAD should
      be combined with the apheresis therapies, DFPP and HF. We believe that this
      concept, a combination of HF and DFPP with therapeutic LVAD, will be the next
      generation of treatment that has a potential to postpone, or even avoid, heart
      transplantation.

PMID- 14961958
TI  - Development of a cultured dermal substitute composed of a spongy matrix of
      hyaluronic acid and atelo-collagen combined with fibroblasts: cryopreservation.
AB  - An allogeneic cultured dermal substitute (CDS) was prepared by cultivating
      fibroblasts on a two-layered spongy matrix of hyaluronic acid (HA) and atelo
      collagen (Col). The ability of fibroblasts to secrete cytokines is dependent on
      the conditions of freezing and thawing. The first experiment was designed to
      investigate the effects of supplements in a cryoprotective medium, that is,
      dimethylsulfoxide (DMSO), glycerol, and fetal bovine serum (FBS). In each
      experiment we measured the cell viability after thawing and the cell growth in
      CDS recultured after thawing. In addition, the amount of vascular endothelial
      growth factor (VEGF) released from the CDS recultured for one week after thawing
      was measured. The highest values of cell viability, cell growth, and the amount
      of VEGF released were obtained when CDS was frozen in Dulbecco's modified Eagle's
      medium (DMEM) supplemented with 10% DMSO and 40% FBS, and then thawed quickly in
      a water bath at 37 degrees C. However, due to the high cost of FBS, in clinical
      applications CDS is usually frozen in DMEM supplemented with 10% DMSO and 20%
      FBS. In practice, however, physicians often cannot use CDS immediately after
      thawing, depending on clinical conditions. Therefore, in the second experiment we
      investigated cell viability at different time points after thawing. In addition,
      we investigated cell growth and the amount of VEGF released from fibroblasts in
      CDS at different time points after thawing under different conditions, and after
      further reculturing for one week. We recommend that CDS be rinsed with lactated
      Ringer's solution immediately after thawing, and that it be used within 4 h after
      thawing.

PMID- 14961959
TI  - Outcome of the perioperative use of percutaneous cardiopulmonary support for
      adult cardiac surgery: factors affecting hospital mortality.
AB  - Percutaneous cardiopulmonary bypass support (PCPS) has become a widespread
      standard modality for the treatment of circulatory collapse; however, its
      clinical use for postcardiotomy low cardiac output syndrome (LOS) has been
      reported to be unsatisfactory. We reviewed the clinical outcomes of twenty-three
      patients undergoing cardiac surgery and treated with PCPS. Solitary coronary
      artery grafting was undertaken for nine patients, while three had concomitant
      procedures. The remaining patients underwent valvular surgery. The indications
      for PCPS were preoperative shock in two patients and postcardiotomy LOS or shock
      in twenty-one patients. All patients except one underwent an intraaortic balloon
      pump. Sixteen of the twenty-three patients (69.6%) were weaned from PCPS and
      twelve patients (52.2%) reached hospital discharge. A univariate analysis
      revealed that risk factors for hospital mortality were age older than seventy
      years (P = 0.05), PCPS running time (P = 0.017), low cardiac function at the
      institution of PCPS (P = 0.004), and urine output within the initial 24 h (P =
      0.041). The cardiac index (CI) in survivors was improved within 24 h, and eleven
      of the twelve survivors were weaned off PCPS within 48 h, whereas ten of the
      twelve nonsurvivors required PCPS for more than 48 h (P = 0.0006). There is
      little possibility of weaning patients from PCPS who do not show any signs of
      hemodynamic recovery within 48 h after its institution. Limited use of PCPS
      within 48 h may be applicable for postcardiotomy patients, but other
      cardiopulmonary support, such as a left ventricular assist device, may be
      required when hemodynamic recovery is not obtained within 48 h.

PMID- 14961960
TI  - Mathematical modeling of fluid dynamics in pulsatile cardiopulmonary bypass.
AB  - The design criteria of an extracorporeal circuit suitable for pulsatile flow are
      quite different and more entangled than for steady flow. The time and costs of
      the design process could be reduced if mutual influences between the pulsatile
      pump and other extracorporeal devices were considered without experimental trial
      and-error activities. With this in mind, we have developed a new lumped-parameter
      mathematical model of the hydraulic behavior of the arterial side of an
      extracorporeal circuit under pulsatile flow conditions. Generally, components
      feature a resistant-inertant-compliant behavior and the most relevant
      nonlinearities are accounted for. Parameter values were derived either by
      experimental tests or by analytical analysis. The pulsatile pump is modeled as a
      pure pulsatile flow generator. Model predictions were compared with flow rate and
      pressure tracings measured during hydraulic tests on two different circuits at
      various flow rates and pulse frequencies. The normalized root mean square error
      did not exceed 24% and the model accurately describes the changes that occur in
      the basic features of the pressure and flow wave propagating from the pulsatile
      pump to the arterial cannula.

PMID- 14961961
TI  - Pyrogen transfer across high- and low-flux hemodialysis membranes.
AB  - The extent to which bacterial products from contaminated dialysate enter a
      patient's blood depends upon the type and permeability of the hemodialysis
      membrane in use. This study was performed to assess the transfer of pyrogenic
      substances across both high- and low-flux membranes (DIAPES, Fresenius
      Polysulfone, Helixone, Polyamide S). All experiments were carried out in the
      saline-saline model. The dialysate pool was contaminated either with purified
      lipopolysaccharide (LPS) (250 and 500 EU/mL) or with sterile bacterial culture
      filtrates (20 EU/mL), and in vitro dialysis was performed under diffusive and
      convective conditions. A significant transfer of endotoxin was observed for both
      low- and high-flux DIAPES challenged with either LPS or with bacterial culture
      filtrates. Under identical conditions, no transfer of endotoxins was detectable
      across Fresenius Polysulfone and Helixone upon challenge with purified LPS. With
      bacterial culture filtrates, endotoxin concentrations for Polyamide S and
      Fresenius Polysulfone were about 10% and 1%, respectively, of those measured for
      DIAPES, whereas no transfer of endotoxin was detectable for Helixone. Using an
      alternative assay (induction of interleukin-1 receptor antagonist, IL-1Ra, in
      whole blood), only the DIAPES membrane showed the passage of cytokine-inducing
      substances. Thus, when saline is present in both the blood and dialysate
      compartments (i.e., the situation during predialysis priming procedures),
      dialysis membranes differ profoundly with respect to their permeability to
      endotoxins.

PMID- 14961962
TI  - Rotary blood pumps for cardiac assistance: a "must"?
AB  - Ventricular Assist Devices (VADs) were developed following the observation that
      most end-stage heart failure patients only required left heart support for
      survival. The trend toward left VAD implantation instead of a TAH has actually
      contributed to the development of nonpulsatile rotational devices. This article
      intends to evaluate the current and future technology of continuous flow pumps.
      Various issues pertaining to the long-term effects of continuous blood flow,
      biocompatibility of axial flow pumps, and the safety and reliability of such
      devices need to be addressed. Some of the advantages of rotary blood pumps
      include their small size, ease of implantation, and encouraging low infection
      rates. Certain issues such as automatic flow control, device components
      durability, and hemocompatibility remain unresolved. The quest for an ideal
      device combining optimal efficiency, ease of anatomical fit, and perfect
      bioacceptance, continues. Rotary blood pumps are not yet a "must."

PMID- 14961963
TI  - Development of an electro-stethoscope system and design of an optimum filter
      based on tissue sound transmission for noninvasive early diagnosis of malfunction
      of an implanted mechanical total artificial heart.
AB  - Early diagnosis of the malfunction of a mechanical artificial heart implanted in
      a patient who has been discharged from hospital is very important. We have
      developed an electro-stethoscope system that enables the malfunction of an
      artificial heart to be detected from the analysis of sound signals from the
      artificial heart. The sound data can be transmitted to a hospital via a mobile
      telephone or the Internet, so that doctors can examine the condition of the
      artificial heart. The optimum frequency characteristics of a low-pass filter for
      the elimination of ambient sound through the electro-stethoscope casing were
      obtained by simulating sound transmission through tissue. We evaluated the
      usefulness of the electro-stethoscope system using a goat in which an undulation
      pump total artificial heart had been implanted. A frequency analysis of the sound
      signal provided information on the degree of degradation of each mechanical
      component of the artificial heart. The results of this study showed that the
      electro-stethoscope system is useful for the early detection of the malfunction
      of an artificial heart at home, and that the use of the system contributes to
      improvement in the quality of life of patients.

PMID- 14961964
TI  - Symptomatic hypocalcemia due to the inadvertent use of a calcium-free
      hemodialysate.
AB  - Hemodialysis using a bath with less-than-normal calcium level can cause
      hypocalcemia. The development of symptomatic hypocalcemia with resultant
      hypotension after the inadvertent use of a calcium-free dialysate in a
      maintenance hemodialysis patient is described. It is suggested that the
      occurrence of similar mishaps in the future can be reduced by close checking of
      dialysate concentrate labels.

PMID- 14961965
TI  - Biological reactions resulting from endotoxin adsorbed on dialysis membrane: an
      in vitro study.
AB  - Some types of dialysis membrane are known to adsorb endotoxin (ET). It is
      suggested that the biocompatibility of dialysis membrane is enhanced by
      adsorption and inhibition of ET. This study attempts to clarify the membrane
      mediated biological reaction of the ET that is adsorbed to a dialysis membrane.
      After a dialysis circuit was prepared, contaminated dialysate was introduced on
      the dialysate side of a polyether polymer alloy (PEPA) membrane that adsorbs ET
      while saline solution or blood were introduced on the blood side, and the
      difference in ET adsorption between the two set-ups was measured. Further, the
      side filled with blood was left standing for 2 h, after which the changes in the
      amount of interleukin 1 receptor antagonist (IL-1Ra) produced from the whole
      blood were also assayed. Significantly more ET was adsorbed to the dialysis
      membrane when blood rather than saline was on the other side. In addition, the IL
      1Ra production from the dialysis membrane that adsorbed ET was significantly
      higher. The ET adsorbed to the dialysis membrane may influence a living body even
      if it does not pass through the membrane. Accordingly, it is difficult to assume
      that the adsorption of ET to the membrane enhances its biocompatibility.

PMID- 14961966
TI  - Ozonated autohemotherapy in patients on maintenance hemodialysis: influence on
      lipid profile and endothelium.
AB  - Ozonated autohemotherapy (O3-AHT) is used in the treatment of atherosclerotic
      ischemia of lower limbs (AILL). The impact of ozone on serum lipids and
      endothelium injury is of particular interest since these factors are important in
      the development of atherosclerotic lesions. To evaluate this issue, a
      prospective, placebo-controlled study was designed. Twelve hemodialyzed subjects
      with AILL received autohemotherapy with oxygen as a control followed by O3-AHT
      with ozone concentration of 50 micro g/ml. Serum lipids and plasma activity of
      von Willebrand factor (vWF) were measured. After O3-AHT, total cholesterol
      significantly decreased compared to the baseline (-8.34%) [P < 0.01]. LDL
      cholesterol was also significantly lower than the initial value (-17.71%) [P <
      0.001]. No significant changes in the activity of vWF were found after the first
      session of O3-AHT and after all nine sessions of O3-AHT. The study demonstrated
      that O3-AHT did not affect deleteriously the endothelium in patients with chronic
      renal failure on maintenance hemodialysis. It may stimulate beneficial changes in
      serum lipid profile manifesting as a decrease in the total- and LDL-cholesterol
      levels.

PMID- 14961967
TI  - Eighty years in the service of science.

PMID- 14961968
TI  - Colorectal xanthomas with polypoid lesion: report of 25 cases.
AB  - Little attention has been paid to colorectal xanthoma. To clarify the clinical
      and pathological features of colorectal xanthoma, we report 28 colorectal
      xanthomas biopsied from 25 patients. All were composed of typical xanthoma cells
      and showed polypoid configuration. Median age of the patients was 64 years and
      there were 15 men and 10 women. Diabetes mellitus, constipation, and
      hyperlipidemia were found in two, one, and seven patients, respectively.
      Seventeen (60.7%) of the 28 polyps were located in the sigmoid colon and the
      remaining 11 in the rectum. Twenty-three polyps (82.1%) were sessile. Twelve
      (60.0%) of twenty polyps that were recorded were reddish in color. Only two
      polyps revealed a yellowish tone. Microscopically, foamy cells were present in
      the lamina propria, but the submucosa did not contain foamy cells.
      Immunohistochemically, the foamy cells invariably expressed extensive positivity
      for CD68. The colonic glands showed a deformity in the case with moderate to
      intense density of the foamy cells. The surface epithelium showed a hyperplastic
      change in 22 (78.6%) xanthomas. The colonic glands in four xanthomas were also
      associated with hyperplastic changes. The basement membrane of the surface
      epithelium was often thickened. Cell debris and proliferation of the capillaries
      were observed just below the surface epithelium in 19 (67.9%) and 22 (78.6%)
      xanthomas, respectively. Previous mucosal minute injury was suggested as the
      pathogenesis of colorectal xanthomas. Colorectal xanthomas were not identical to
      gastric and esophageal xanthoma, endoscopically or microscopically. We prefer the
      term "xanthomatous polyp" rather than xanthoma in the colorectal region. They may
      be regarded as a novel type of colorectal non-neoplastic polyp.

PMID- 14961969
TI  - Histo-blood group ABO antigen in oral potentially malignant lesions and squamous
      cell carcinoma--genotypic and phenotypic characterization.
AB  - Loss of histo-blood group A/B antigens is frequent in oral cancer. It is unclear
      whether this alteration is due to loss of the chromosomal region encoding the
      genes. The aim was to investigate genotypic alterations in the ABO locus in oral
      potentially malignant lesions and carcinomas. Seventy-three cases which expressed
      A/B antigen in normal epithelium by immunohistochemical (IHC) staining were
      investigated. Both tumour and normal cells were collected from paraffin-embedded
      tissue by laser microdissection. DNA was extracted and analysed by PCR coupled
      with restricted digestion analysis in order to establish the ABO genotype. Total
      and patchy loss of A/B antigen expression was found in 24/32 carcinomas, 6/7
      leukoplakias with severe dysplasia, 12/17 leukoplakias with mild and moderate
      dysplasia, and 6/17 leukoplakias without dysplasia. Specific A/B allele loss was
      found in 8/24 cases with carcinoma and 3/24 cases with mild and moderate
      dysplasia by genotyping analysis. O allele loss was found in 10 cases involving
      all four groups. In patients with heterozygous genotypes, A/B allelic loss by
      genotyping analysis was always followed by loss of A/B antigen expression by IHC
      staining. Loss of A/B antigen expression in tissues which had intact ABO alleles
      was, however, found and may be explained by other genetic and epigenetic changes.

PMID- 14961970
TI  - A comparative study of the allergenic potency of wild-type and glyphosate
      tolerant gene-modified soybean cultivars.
AB  - A large proportion of soybean cultivars grown in the USA are now genetically
      modified varieties and concern has been raised about the safety of these products
      for consumers. A study of the impact on allergenic potency in soybeans,
      comparable except for the newly introduced gene (CP4 EPSPS), was performed using
      soybean-sensitized patients. The allergenicity of 18 different (10 GM and 8 WT)
      soybean extracts was examined blindly by the following three methods: A) Sera
      from patients with specific IgE against soybean were used to determine
      concentrations inducing 50% RAST inhibition; B) Histamine release induced by the
      extracts was examined using blood from sensitized patients; C) SPT was performed
      on sensitized patients with all 18 extracts. All three methods showed variations
      in the allergenic potency between the individual extracts but allergenic
      potential was not affected by presence of the transgene. By using standard in
      vitro methods and SPT for determination of allergenicity we were not able to
      detect any significant difference in the allergenic potency between GM and WT
      soybeans.

PMID- 14961971
TI  - Adenoma of the esophagus with intracytoplasmic mucoid bodies.
AB  - We report a tubular adenoma of the esophagus in a 79-year-old man. The tumour had
      progressed to an intramucosal carcinoma at follow-up 6 months later. The adenoma
      displayed a peculiar and heterogeneous histological picture with non-dysplastic
      and cystic areas alternating with those of a typical tubular adenoma. The tumour
      revealed a strong and diffuse expression of cytokeratin 7 and basal cell
      cytokeratin, whereas cytokeratin 20 was focally positive only. The most
      remarkable finding, however, was the demonstration of intracytoplasmic inclusion
      like mucoid bodies of the epithelial cells in a small area of the adenomatous
      component. These inclusions stained PAS positive and alcian blue negative, and
      electron microscopy revealed a homogeneous structure without viral-like
      particles.

PMID- 14961972
TI  - Accelerated decline in Helicobacter pylori seroprevalence rate during the screen
      and treat project in Vammala, Finland, as demonstrated in 29- to 45-year-old
      pregnant women.
AB  - The potential preventability of serious helicobacter-associated diseases -
      especially gastric cancer - has evoked interest in eradicating this pathogen from
      the population. We assessed the efficacy of the pioneering screen and treat
      intervention project in Vammala by studying helicobacter seroprevalence in
      pregnant women representing the normal population. Consecutive maternity clinic
      samples from native Finnish females at five different localities in 1995 (n=701)
      and 2000 (n=772) were investigated for class IgG H. pylori antibodies by enzyme
      immunoassay (Pyloriset EIA-G III, Orion Diagnostica, Espoo, Finland). In Vammala
      the change in helicobacter seroprevalence was -13%-units (between 1995 and 2000;
      p=0.0125, chi-square test) in > or =29-year-old females, +1.6%-units (difference
      statistically non-significant) in <29-year-old females, and -5.5%-units
      (difference statistically non-significant) in the whole study population. In the
      four reference localities studied, all the corresponding changes remained
      statistically non-significant. Thus, in Vammala the programme applied accelerated
      the decline of helicobacter infections in 29- to 45-year-old females and in 2000
      the seroprevalence rate had also become significantly lower than that of the four
      reference communities combined (7.6% versus 13.5%, respectively, p=0.0433, chi
      square test). The final outcome of the intervention project, i.e. the long-term
      effect of this decline on gastric cancer and peptic ulcer disease, remains to be
      evaluated.

PMID- 14961973
TI  - Expression of cyclin A in Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a rare and aggressive primary neuroendocrine
      carcinoma of the skin. Large tumours, in particular, show rapid progression and
      metastatic dissemination, while smaller tumours show less aggressive behaviour.
      Cyclin A is considered to play a central role in cell cycle control. Its
      overexpression has been found to correlate with prognosis in many types of
      carcinomas and sarcomas. Twenty-six MCC patients with complete clinical data were
      selected. Formalin-fixed paraffin-embedded primary tumour samples were
      immunohistochemically stained for cyclin A. Correlation between expression of
      cyclin A and primary tumour size, invasion of subcutaneous tissue, local
      recurrence, metastasis and survival was statistically analysed. Twenty-five
      samples expressed cyclin A, and the mean value of positive cells was 25%. Our
      findings demonstrate that even small and superficial MCC show overexpression of
      cyclin A. There was no statistical correlation between cyclin A expression and
      the above-mentioned variables. Cyclin A does not seem to be useful as a
      prognostic tool. Consequently, size of the primary tumour (>/=2 cm) remains the
      primary prognostic tool. As a result every tumour, even those small in size,
      should be considered aggressive and treated radically and rapidly.

PMID- 14961974
TI  - Tumor-like cystic endosalpingiosis of the uterus with florid epithelial
      proliferation. A case report.
AB  - Mass-like cystic endosalpingiosis is very rare. The author reports such a lesion
      with histologic features of endosalpingiosis of the uterus with florid epithelial
      proliferation in a 51-year-old female who complained of lower abdominal pain.
      Preoperatively, it was considered to be left-sided ovarian cancer.
      Intraoperatively, a subserosal, sessile polypoid mass with multiple cysts in the
      uterine fundus measuring 12 x 6.5 x 5.5 cm was found. Histologically, it was
      composed of multiple cysts lined by benign-appearing tubal epithelium and bland
      smooth muscular and myofibromatous stroma. Part of the epithelium exhibited
      marked papillarity and tufting. Features of conventional endometriosis were
      present focally. Pathologists and clinicians should be aware of the existence of
      this type of non-neoplastic lesion, mass-like cystic endosalpingiosis, and should
      avoid overdiagnosis and overtreatment.

PMID- 14961975
TI  - Expression of non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1
      in relation to patient outcome in human colon adenocarcinomas.
AB  - Non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 are key
      participants in the Wnt cell signalling pathway, in which aberrancies have been
      associated with malignant cell transformation. We assessed the independent
      prognostic value of these proteins in a clinical material. Tumours from a series
      of 162 patients operated on for Dukes' stage A, B and C colonic adenocarcinomas
      were analysed using semiquantitative immunohistochemistry and the results were
      related to patient outcome. Patients expressing nuclear beta-catenin in the
      primary tumour showed reduced survival compared to other patients (log rank
      p=0.028) and there was also an association with development of metastases follow
      up (logistic regression p=0.024). Using multivariate analysis (Cox regression) co
      expression of nuclear beta-catenin and c-Myc turned out to be the strongest
      marker of impaired prognosis (p=0.001, HR 5.26, 95% CI 1.93-14.36). Expression of
      non-membranous gamma-catenin, cyclin D1 and c-Myc alone failed to have
      independent prognostic significance in our study.

PMID- 14961976
TI  - Induction of cystic forms by different stress conditions in Borrelia burgdorferi.
AB  - Cystic forms of Borrelia burgdorferi might represent a low metabolic activity
      state or phase of B. burgdorferi cells that allows the spirochete to survive in a
      hostile environment until conditions are favourable to multiply again. In this
      study we evaluated the rate of cyst formation induced by oxidative stress, pH
      variations, and heating, reconversion of cysts to vegetative forms, and some
      aspects of their metabolic activity. We observed cyst formation in the presence
      of extreme pH values, and at high temperature, but the best production of cystic
      forms was observed in the presence of H2O2. When transferred to BSK II medium,
      the cystic forms reconverted to spirochetes in relation to their age and type of
      induction treatment. Furthermore, we demonstrated a low metabolic activity of
      cystic forms by measuring amino acid incorporation. Overall, these data suggest
      that the phenomenon of conversion to cysts by B. burgdorferi provides a limited
      survival potential. This short-term survival, however, gives borreliae an
      additional chance to overcome unfavourable environmental conditions.

PMID- 14961977
TI  - Involution of thymus and lymphoid depletion in mice expressing the hTNF
      transgene.
AB  - Tumour necrosis factor (TNF) is involved in the pathogenesis of several diseases.
      In mice, human TNF signals only through p55, one of two murine TNF receptors. We
      here report a study of growth, viability and morphological alterations in
      transgenic mice expressing a low constitutive and tissue-restricted level of
      human TNF in vivo. The transgene was expressed solely in T cells. The transgenic
      mice showed a marked failure to thrive and a rapid cellular depletion in spleen
      and thymus. Slight fibrosis was seen in most tissues investigated, in addition to
      immature adipose tissue and irregular lymphocytic areas. Serum levels of hTNF
      were only slightly increased in the transgenic mice, enough, however, to cause an
      inflammatory reaction. All the symptoms were abrogated by an inhibitory hTNF
      antibody, demonstrating the essential role of hTNF in this phenotype. Transgenic
      mice constitute a multidimensional system allowing observation of disease
      processes over time in all tissues. The effects of hTNF were seen first and
      foremost in the lymphoid organs of the transgenic mice, verifying their cells as
      major targets at low levels of hTNF expression in the T-cell compartments.
      Chronic, low levels of TNF expression cause profound disturbances in lymphoid
      tissue development resulting in cachexia and premature death.

PMID- 14961978
TI  - Lyme borreliosis in Sweden--diagnostic performance of five commercial Borrelia
      serology kits using sera from well-defined patient groups.
AB  - Five commercial Borrelia serology kits available in Sweden were evaluated and
      compared for their diagnostic performance in sera from clinically well
      characterized patient groups. With the clinically defined groups as the gold
      standard, i.e. without knowledge of antibody status in serum and cerebrospinal
      fluid, the diagnostic performance of the kits was compared and important
      differences in diagnostic usefulness were found. The kits from Abbot and DAKO,
      that often predict clinically relevant Borrelia infection and do not detect
      antibodies in sera from patients without strong suspicion of Borrelia infection,
      were considered the most useful in the population studied. This kind of
      validation study is an important part of good laboratory practice and should be
      performed by laboratories serving patient populations with varying endemicity of
      Borrelia.

PMID- 14961979
TI  - Living donor liver transplantation in children: what to recommend?

PMID- 14961980
TI  - Unraveling the secrets of single donor success in islet transplantation.

PMID- 14961981
TI  - From pharmacokinetics to pharmacogenomics: a new approach to tailor
      immunosuppressive therapy.
AB  - One of the main tasks in the management of organ transplantation is the
      optimization of immunosuppressive therapy, in order to provide therapeutic
      efficacy limiting drug-related toxicity. In the past years major efforts have
      been carried out to define therapeutic windows based on blood/plasma levels of
      each immunosuppressant relating those concentrations to drug dosing and clinical
      events. Although this traditional approach is able to identify environmental and
      nongenetic factors that can influence drug exposure during the course of
      treatment, it presents limitations. Therefore, complementary strategies are
      advocated. The advent of the genomic era gives birth to pharmacogenomics, a
      science that studies how the genome as a whole, including single genes as well as
      gene-to-gene interactions, may affect the action of a drug. This science is of
      particular importance for drugs characterized by a narrow therapeutic index, such
      as the immunosuppressants. Preliminary studies focused on polymorphisms of genes
      encoding for enzymes actively involved in drug metabolism, drug transport and
      pharmacological target. Pharmacogenomics holds promise for improvement in the
      ability to individualize immunosuppressive therapy based on the patient's genetic
      profile, and can be viewed as a support to traditional therapeutic drug
      monitoring. However, the clinical applicability of this approach is still to be
      proven.

PMID- 14961982
TI  - Beyond C4d: other complement-related diagnostic approaches to antibody-mediated
      rejection.
AB  - Complement is a multifunctional system of receptors and regulators as well as
      effector molecules. Both the pathogenic and diagnostic power of complement is
      based on the capacity of the complement system to amplify innate and adaptive
      immunity. This amplification is accomplished through two strategies: (1)
      enzymatic reactions in the complement cascade, and (2) stimulation of leukocytes,
      platelets and parenchymal cells through specific receptors or receptor
      independent pore formation. The mechanisms by which complement mediates and
      modifies nonspecific inflammation, antibody-mediated injury and T-cell responses
      are of particular significance to the pathogenesis of transplant rejection.
      Understanding the mechanisms by which complement integrates the interactions of
      leukocytes, platelets and parenchymal cells offers opportunities to further
      refine the diagnosis of rejection.

PMID- 14961983
TI  - Airway epithelium is the primary target of allograft rejection in murine
      obliterative airway disease.
AB  - Murine heterotopic tracheal allografts develop obliterative airway disease (OAD),
      a suitable model of chronic lung allograft rejection. This model, however, fails
      to account for the behavior of the allograft when adjacent to recipient airway
      tissues, particularly the epithelium. This study was performed to determine the
      immunologic role of the epithelium in development of OAD. BALB/c (H2d) tracheal
      allografts were transplanted orthotopically into C57BL/6 (H2b) mice and harvested
      14-150 days post-transplantation. The phenotype of the allograft epithelium after
      orthotopic transplantation was determined with immunofluorescent staining.
      Orthotopic BALB/c tracheal allografts harvested at 28 days were re-transplanted
      heterotopically into BALB/c or C57BL/6 mice, harvested after 28 days, and
      assessed for OAD. Orthotopic allografts displayed mild cellular infiltration, no
      fibrosis and preserved epithelium at 28 days post-transplant. The presence of
      recipient-derived epithelium within the allograft was demonstrated with
      immunofluorescent staining at day 14. Significantly, BALB/c orthotopic allografts
      re-transplanted heterotopically into BALB/c mice developed OAD by day 28, whereas
      BALB/c orthotopic allografts re-transplanted heterotopically into C57BL/6 mice
      did not. Repopulation of orthotopic tracheal allografts with recipient-derived
      epithelium confers a protective effect against OAD after heterotopic re
      transplantation. This indicates that the airway epithelium plays a crucial role
      in OAD development.

PMID- 14961984
TI  - Non-complement- and complement-activating antibodies synergize to cause rejection
      of cardiac allografts.
AB  - Alloantibodies (AlloAbs) are a clinically significant component of the immune
      response to organ transplants. In our experimental model, B10.A (H-2a) cardiac
      transplants survived significantly longer in C57BL/6 (H-2b) immunoglobulin knock
      out (IgKO) recipients than in their wild-type (WT) counterparts. Passive transfer
      of a single 50-200-microg dose of complement-activating IgG2b AlloAbs to IgKO
      recipients reconstituted acute rejection of cardiac allografts. Although passive
      transfer of a subthreshold dose of 25 microg of IgG2b or a single 100-200-microg
      dose of non-complement-activating IgG1 AlloAbs did not restore acute rejection to
      IgKO recipients, a combination of these AlloAbs did cause acute graft rejection.
      Histologically, rejection was accompanied by augmented release of von Willebrand
      factor from endothelial cells. IgG1 AlloAbs did not activate complement on their
      own and did not augment complement activation by IgG2b AlloAbs. However, IgG1
      AlloAbs stimulated cultured mouse endothelial cells to produce monocyte
      chemotactic protein 1 (MCP-1) and neutrophil chemoattractant growth-related
      oncogene alpha (KC). TNF-alpha augmented IgG1 induced secretion of MCP-1 and KC.
      These findings indicate that non-complement-activating AlloAbs can augment injury
      to allografts by complement-activating AlloAbs. Non-complement-activating AlloAbs
      stimulate endothelial cells to produce chemokines and this effect is augmented in
      the milieu of proinflammatory cytokines.

PMID- 14961985
TI  - Alterations in the coagulation profile in renal pig-to-monkey
      xenotransplantation.
AB  - Five monkey recipients of a porcine renal xenograft were studied to determine the
      relationship between fibrin formation in acute humoral xenograft rejection (AHXR)
      and procoagulant and anticoagulant factor levels to establish whether changes in
      coagulation parameters could be used to predict AHXR and determine whether AHXR
      is associated with overt disseminated intravascular coagulopathy (DIC) in this
      model. Variable degrees of compensated consumptive coagulopathy were observed in
      each primate. Elevated thrombin-antithrombin (TAT), F1+2 and D-dimer levels
      consistent with thrombin generation and fibrin formation were recorded. There was
      no consumption of the main clotting inhibitors (including antithrombin) or a
      progressive, severe drop in fibrinogen levels and platelet counts, although
      grafts were left in situ. After transplantation, D-dimer levels remained
      persistently high, so they were of limited value in defining this coagulopathy.
      At post mortem, no cases of multiorgan involvement typical of overt DIC were
      observed. The lack of a rapid postoperative recovery of clotting inhibitor levels
      after transplantation was invariably associated with early poor outcome. This
      study shows that AHXR is associated with various degrees of compensated
      consumptive coagulopathy in our pig-to-primate model. No clear relationship was
      found between coagulation parameter levels and graft outcome.

PMID- 14961986
TI  - Proinflammatory response of alveolar type II pneumocytes to in vitro hypoxia and
      reoxygenation.
AB  - Type II pneumocytes (T2P) are integral in preserving the integrity of the
      alveolar space by modulating the fluid composition surrounding the alveolar
      epithelium. There is also mounting evidence supporting their contribution to the
      development of acute inflammatory lung injury subsequent to oxidative stress.
      This study characterized the response of T2P to in vitro hypoxia and
      reoxygenation (H&R). Rat T2P from a cultured cell line (RLE-6TN) were rendered
      hypoxic for 2 h, and reoxygenated for up to 6 h. Activation of signaling kinases,
      the nuclear translocation of proinflammatory transcription factors, and
      quantification of secreted cytokine and chemokine protein content were assessed.
      Type II pneumocytes expressed activated extracellular signal regulated kinase
      (ERK) 1/2 maximally at 15 min of reoxygenation. C-jun n-terminal kinase (JNK) and
      p38 activation was minimal at all time points studied. The nuclear translocation
      of nuclear factor kappa B (NFkappaB) and activator protein (AP)-1 were dramatic
      after 15 min of reoxygenation. There was a significant increase in the protein
      secretion of CINC (p = 0.03), IL-1beta (p = 0.02), and monocyte chemoattractant
      protein-1 (p < 0.001) at 6 h of reoxygenation. Type II pneumocytes respond
      directly to H&R. ERK 1/2 activity peaks at 15 min of reoxygenation, and
      correlates temporally with the nuclear translocation of NFkappaB and AP-1. These
      signaling cascades likely promote the elaboration of proinflammatory mediators.

PMID- 14961987
TI  - Mitochondrial calcium uptake regulates cold preservation-induced Bax
      translocation and early reperfusion apoptosis.
AB  - Mitochondrial calcium (mCa + 2) overload occurs during cold preservation and is
      an integral part of mitochondrial-dependent apoptotic pathways. We investigated
      the role of mCa + 2 overload in cell death following hypothermic storage using
      HepG2 cells stored in normoxic-hypothermic (4 degrees C) or hypoxic (< 0.1% O2)
      hypothermic Belzer storage solution. Cells were stored for 6 h, with or without
      10 microM ruthenium red (mCa + 2 uniporter inhibitor) followed by rewarming in
      oxygenated media at 37 degrees C. Cytoplasmic cytochrome c levels were studied by
      Western analysis and by fluorescent microscopy after transfection of cytochrome c
      GFP expression plasmid. Immunofluorescence determined the intracellular, spatio
      temporal distribution of Bax, and TUNEL staining was used to evaluate cell death
      after 180 min of rewarming. Caspase activation was evaluated using Western
      analysis and a caspase 3 activity assay. Bax translocation, cytochrome c release,
      and early rewarming cell death occurred following hypothermic storage and were
      exacerbated by hypoxia. Caspase 3 activation did not occur following hypothermic
      storage. Blockade of mCa + 2 uptake prevented Bax translocation, cytochrome c
      release, and early rewarming cell death. These studies demonstrate that mCa + 2
      uptake during hypothermic storage, both hypoxic and normoxic, contributes to
      early rewarming apoptosis by triggering Bax translocation to mitochondria and
      cytochrome c release.

PMID- 14961988
TI  - Suppression of natural and elicited antibodies in pig-to-baboon heart
      transplantation using a human anti-human CD154 mAb-based regimen.
AB  - Natural and elicited antipig antibodies (Abs) lead to acute humoral xenograft
      rejection (AHXR). Ten baboons underwent heterotopic heart transplantation (Tx)
      from human decay-accelerating factor (hDAF) pigs. Depletion of anti-Galalpha1,
      3Gal (Gal) Abs was achieved by the infusion of a Gal glycoconjugate from day-1.
      Immunosuppression included induction of antithymocyte globulin, thymic
      irradiation, and cobra venom factor, and maintenance with a human antihuman CD154
      mAb, mycophenolate mofetil, and methylprednisolone; heparin and prophylactic
      ganciclovir were also administered. Pig heart survival ranged from 4 to 139 (mean
      37, median 27) days, with three functioning for >50 days. Graft failure (n = 8)
      was from classical AHXR [4], thrombotic microangiopathy [3], or intragraft
      thrombosis [1], with death (n = 2) from pneumonia [1], or possible drug toxicity
      (with features of thrombotic microangiopathy) [1]. Anti-Gal Abs (in microg/mL)
      were depleted by Gal glycoconjugate before graft implantation from means of 41.3
      to 6.3 (IgM) and 12.4-4.6 (IgG), respectively, and at graft excision were 6.3 and
      1.7 microg/mL, respectively. No elicited Abs developed, and no cellular
      infiltration was seen. The treatment regimen was effective in maintaining low
      anti-Gal Ab levels and in delaying or preventing AHXR. The combination of
      costimulatory blockade and heparin with Tx of a Gal-negative pig organ may
      prolong graft survival further.

PMID- 14961989
TI  - Influence of graft type on outcomes after pediatric liver transplantation.
AB  - We sought to determine which type of donor graft provides children and young
      adults with the best outcomes following liver transplantation. Using the US
      Scientific Registry of Transplant Recipients database, we identified 6467
      recipients of first liver transplants during 1989-2000 aged < 30 years. We used
      Cox models to examine adjusted patient and graft outcomes by age (< 2, 2-10, 11
      16, 17-29) and donor graft type (deceased donor full size (DD-F), split (DD-S),
      living donor (LD)]. For patients aged < 2, LD grafts had a significantly lower
      risk of graft failure than DD-S (RR = 0.49, p < 0.0001) and DD-F (RR = 0.70, p =
      0.02) and lower mortality risk than DD-S (RR = 0.71, p = 0.08) during the first
      year post-transplant. In contrast, older children exhibited a higher risk of
      graft loss and a trend toward higher mortality associated with LD transplants. In
      young adults, DD-S transplants were associated with poor outcomes. Three-year
      follow up yielded similar graft survival results but no significant differences
      in mortality risk by graft type within age group. For recipients aged < 2, LD
      transplants provide superior graft survival than DD-F or DD-S and trend toward
      better patient survival than DD-S. Living donor is the preferred donor source in
      the most common pediatric age group (< 2 years) undergoing liver transplantation.

PMID- 14961990
TI  - Lack of improvement in renal allograft survival despite a marked decrease in
      acute rejection rates over the most recent era.
AB  - Acute rejection is known to have a strong impact on graft survival. Many studies
      suggest that very low acute rejection rates can be achieved with current
      immunosuppressive protocols. We wanted to investigate how acute rejection rates
      have evolved on a national level in the U.S. and how this has impacted graft
      survival in the most recent era of kidney transplantation. For this purpose, we
      analyzed data provided by the Scientific Registry of Transplant Recipients
      regarding all adult first renal transplants between 1995 and 2000. We noted a
      significant decrease in overall acute rejection rates during the first 6 months,
      during the first year, and also in late rejections during the second year after
      transplantation. Despite this decrease in the rate of acute rejection, there was
      no significant improvement in overall graft survival; furthermore, we noted a
      statistically significant trend towards worse death-censored graft survival.
      There was also a trend for a greater proportion of rejection episodes to fail to
      recover to previous baseline function after treatment. Our data suggest that
      decreasing acute rejection rates between 1995 and 2000 have not led to an
      increase in long-term graft survival. Part of this discordance might be related
      to a higher proportion of acute rejections which have not resolved with full
      functional recovery in more recent years. However, the etiology of this
      concerning trend for worse death censored graft survival in recent years will
      warrant further investigation.

PMID- 14961991
TI  - Post-transplant infections now exceed acute rejection as cause for
      hospitalization: a report of the NAPRTCS.
AB  - Newer immunosuppressive agents have dramatically reduced the rates of acute graft
      rejection (AR) over the last decade but may have exacerbated the problem of post
      transplant infections (PTI). We analyzed data from the North American Pediatric
      Renal Transplant Cooperative Study (NAPRTCS) to determine the risks of
      hospitalization from PTI vs. AR in the years 1987-2000. For patients transplanted
      in 1987, the AR-associated hospitalization rate exceeded the equivalent
      hospitalization rate for PTI at both early (1-6 months) and later time points (6
      24 months). In contrast, for patients transplanted in the year 2000, the PTI
      associated hospitalization rate was twice that for AR-associated hospitalization
      during each time period. During the first two years post-transplant, rates of AR
      hospitalization trended significantly downwards (p < 0.001) while rates of PTI
      associated hospitalization stayed constant. In the 6-24-month time period post
      transplant, the risk of bacterial and viral infection-related hospitalization
      rose significantly from 1987 to 2000 (p < 0.001 for trend by transplant year). We
      conclude that the causes of hospitalization at all times up to 24 months post
      transplant, including the critical early 6 months, have shifted away from AR to
      PTI.

PMID- 14961992
TI  - Transplantation of cultured islets from two-layer preserved pancreases in type 1
      diabetes with anti-CD3 antibody.
AB  - We sought to determine whether or not optimizing pancreas preservation, islet
      processing, and induction immunosuppression would facilitate sustained diabetes
      reversal after single-donor islet transplants. Islets were isolated from two
      layer preserved pancreata, purified, cultured for 2 days; and transplanted into
      six C-peptide-negative, nonuremic, type 1 diabetic patients with hypoglycemia
      unawareness. Induction immunosuppression, which began 2 days pretransplant,
      included the Fc receptor nonbinding humanized anti-CD3 monoclonal antibody
      hOKT3gamma1 (Ala-Ala) and sirolimus. Immunosuppression was maintained with
      sirolimus and reduced-dose tacrolimus. Of our six recipients, four achieved and
      maintained insulin independence with normal HbA1c levels and freedom from
      hypoglycemia; one had partial islet graft function; and one lost islet graft
      function 2 weeks post-transplant. The four insulin-independent patients showed
      prolonged CD4+ T-cell lymphocytopenia; inverted CD4:CD8 ratios; and increases in
      the percentage of CD4+CD25+ T cells. These cells suppressed the in-vitro
      proliferative response to donor cells and, to a lesser extent, to third-party
      cells. Severe adverse events were limited to a transient rash in one recipient
      and to temporary neutropenia in three. Our preliminary results thus suggest that
      a combination of maximized viable islet yield, pretransplant islet culture, and
      preemptive immunosuppression can result in successful single-donor islet
      transplants.

PMID- 14961993
TI  - Cooperative influence of the interleukin-6 promoter polymorphisms -597, -572 and 
      174 on long-term kidney allograft survival.
AB  - Recently, we demonstrated an association of the IL-6 promoter polymorphism at
      position -174 (G-->C) with kidney allograft survival whereby carriers of the 
      174GG genotype were identified as having superior graft survival. As two
      additional polymorphisms were discovered in the neighborhood at positions -572 (G
      ->C) and -597 (G-->A), respectively, and as functional studies revealed a
      cooperative impact of all three on the IL-6 gene transcription, we investigated
      whether there is a combined effect on kidney transplant outcome. We determined IL
      6 promoter haplotypes -597 (G-->C)/-572 (G-->A)/-174 (G-->C)(-597/-572/
      174haplotype) using a PCR system with sequence-specific primers in 158 patients
      after primary cadaveric kidney transplantation. We here show that the -597 and 
      174 polymorphism are in tight-linkage disequilibrium and that homozygous carriers
      of the GGG-597/-572/-174 haplotype (GGG/GGG genotype) have superior 3-year graft
      survival rates compared with the 8.0-fold increased risk of premature graft loss
      in all other patients. Interestingly, patients carrying the GGG/GCG genotype had
      the lowest allograft survival rate. Thus determination of the combined -597/-572/
      174 genotype allows for further differentiation of -174GG patients into subgroups
      and consequently for a more accurate identification of patients at risk. Our
      results indicate that the three polymorphisms act in a cooperative fashion and we
      provide evidence for an exceptional clinical impact of the IL-6-597/-572/-174
      genotype on the success of kidney transplantation.

PMID- 14961994
TI  - Quality of life after pediatric intestinal transplantation: the perception of
      pediatric recipients and their parents.
AB  - The objective was to examine the perception of physical and psychosocial
      functioning of pediatric intestinal transplant recipients who are beyond the
      perioperative period and compare these with normal and chronically ill children.
      Child and parent forms of the Child Health Questionnaire were administered to all
      29 pediatric intestinal transplant recipients between the ages of 5 and 18 years
      who had had a small bowel transplantation 1 year previous and had a functional
      allograft. Comparison was made with published norms and scores for pediatric
      patients on hemodialysis. Intestinal transplant recipients (on average 5 years
      after intestinal transplantation and at a mean age 11 years) reported similar
      scores in all domains compared with normal children. Parents of intestinal
      transplant recipients noted decreased function in several domains related to
      their child's general health, physical functioning, and the impact of the illness
      on parental time, emotions and family activities. Intestinal transplant
      recipients beyond the perioperative period perceive their physical and
      psychosocial functioning as similar to normal school children. Parental proxy
      assessments differ from the recipients, with the parent's perception of decreased
      general health and physical functioning for intestinal transplant recipients
      compared with norms.

PMID- 14961995
TI  - Defining normal plasma citrulline in intestinal transplant recipients.
AB  - Biopsy is the only means to identify intestinal graft rejection. Plasma
      citrulline (P-Cit) has been proposed as a marker for rejection after intestinal
      transplant (IT), but normative data is lacking. We analyzed P-Cit in IT
      recipients without rejection or other histological abnormalities. In 40 patients,
      P-Cit was measured with a Beckman amino acid analyzer within 24 h of protocol or
      clinically indicated endoscopic biopsy procured > 6 and < 360 days post-IT.
      Measurements included for analysis corresponded to normal (or minimally abnormal)
      biopsies that remained so for 7 days. These criteria were met by 145 samples from
      10 adults and 14 children. Overall mean P-Cit (nmol/mL) was 34.0 +/- 19.9. Mean P
      Cit was 22.2 +/- 13.2 between 6 and 30 days post-IT, 34.9 +/- 17.2 (p = 0.001)
      between 30 and 60 days, 43.6 +/- 15.8 between 60 and 90 days (p = 0.001), then
      stable until the end of the first year. Plasma citrulline was lower in 13
      patients with body surface area (BSA) < or = 1 m2 vs. 11 patients with BSA > or =
      1.1 m2 (p = 0.0001). Plasma citrulline increased linearly during the first 120
      days in both BSA groups (r = 0.573 and r = 0.512; p = 0.0001). Within 3 months
      after IT, variations in P-Cit based on body size and postop interval should be
      considered when evaluating the need for histological confirmation of graft
      dysfunction.

PMID- 14961996
TI  - Impact of donor dopamine on immediate graft function after kidney
      transplantation.
AB  - Optimizing medical donor management may have a considerable impact on
      transplantation outcome. This study investigated the effect of donor dopamine on
      initial graft function in renal allograft recipients, involving 254 consecutive
      recipients of a cadaver kidney, aged 18-74 years, transplanted between 1990 and
      2003. Immunosuppression was based on cyclosporine. Patients were grouped
      according to donor use of dopamine during intensive care. Delayed graft function
      (DGF), and serial creatinine concentrations were compared between the groups.
      Dopamine-treated and -untreated donors were very similar regarding hemodynamics
      and renal function. Delayed graft function occurred in 47/158 treated and 48/96
      untreated kidneys (p = 0.001). Donor dopamine was associated with a more rapid
      decrease of s-creatinine, which became obvious on the first postoperative day. Of
      patients in the treated and untreated group, respectively, 81.9% and 65.8%
      reached a s-creatinine level less than 2 mg/dL during the first month (p =
      0.005). Donor dopamine remained predictive of a normalized s-creatinine level [HR
      1.71; 95% CI 1.22-2.41] after controlling for confounding factors by multivariate
      Cox regression. Donor dopamine is associated with improvements of initial graft
      function after kidney transplantation. The beneficial effect of dopamine is
      achievable without side-effects for the recipients, and correlates with superior
      long-term graft survival.

PMID- 14961997
TI  - Impact of adult living donor liver transplantation on waiting time survival in
      candidates listed for liver transplantation.
AB  - Studies comparing adult living donor liver transplantation to deceased donor
      liver transplantation have focused on post-transplant survival. Our aim was to
      focus on the impact of living donor liver transplant on waiting time mortality
      and overall mortality. We analyzed the affect of living donor liver
      transplantation on waiting time mortality and overall mortality (from listing
      until last follow up) in a cohort of 116 transplant candidates. Fifty-eight
      candidates who had individuals present as potential living donors (volunteer
      group) were matched by MELD score to 58 liver transplant candidates who did not
      have individuals present as a potential living donor (no volunteer group). Twenty
      seven percent of candidates in the no volunteer group and 62% of candidates in
      the volunteer group underwent liver transplantation, p = 0.0003. One-year waiting
      list mortality for the volunteer group and no volunteer group was 10% and 20%,
      respectively, p = 0.03. Patient survival from the time of listing to last follow
      up was similar between the two groups. In our study group, living donor liver
      transplantation is associated with a higher rate of liver transplantation and
      lower waiting time mortality. In the era of living donor liver transplantation,
      estimates of patient survival should incorporate waiting time mortality.

PMID- 14961998
TI  - Elevation of CXCR3-binding chemokines in urine indicates acute renal-allograft
      dysfunction.
AB  - A noninvasive urinary test that diagnoses acute renal allograft dysfunction would
      benefit renal transplant patients. We aimed to develop a rapid urinary diagnostic
      test by detecting chemokines. Seventy-three patients with renal allograft
      dysfunction prompting biopsy and 26 patients with stable graft function were
      recruited. Urinary levels of CXCR3-binding chemokines, monokine induced by IFN
      gamma (Mig/CXCL9), IFN-gamma-induced protein of 10 kDa (IP-10/CXCL10), and IFN
      inducible T-cell chemoattractant (I-TAC/CXCL11), were determined by a particle
      based triplex assay. IP-10, Mig and I-TAC were significantly elevated in renal
      graft recipients with acute rejection, acute tubular injury and BK virus
      nephritis. Using 100 pg/mL as the threshold level, both IP-10 and Mig had
      diagnostic value (sensitivity 86.4%; specificity 91.3%) in differentiating acute
      graft dysfunction from other clinical conditions. In terms of monitoring the
      response to antirejection therapy, this urinary test is more sensitive and
      predictive than serum creatinine. These results indicate that this rapid test is
      clinically useful.

PMID- 14961999
TI  - Predicting kidney graft failure by HLA antibodies: a prospective trial.
AB  - HLA antibodies have been shown to be associated with late graft loss of organ
      transplants in prior studies. Recently they were even shown to appear years
      BEFORE rejection. (1) An international cooperative study of 4763 patients from 36
      centers was undertaken to determine the frequency of HLA antibodies in patients
      with functional transplants. The overall frequency of HLA antibodies among kidney
      transplant recipients was 20.9%; 19.3% in the liver, 22.8% in the heart, and
      14.2% in the lung. Patients treated with CsA-MMF had significantly lower
      antibodies (9.8%) than those treated with CsA-Aza (18.1%) (0.00008). (2) Second,
      a prospective trial was performed in 23 kidney transplant centers to determine
      whether HLA antibodies could predict failures within 1 year. Among the 2278
      patients followed up, 91 grafts failed and 34 patients died. Of 500 patients who
      had HLA antibodies, 6.6% failed compared with 3.3% among 1778 patients without
      antibodies (p = 0.0007). Among 244 patients who made de novo antibodies, 8.6%
      failed compared with 3.0% failures among 1421 patients who did not make
      antibodies (p = 0.00003). Death occurred in 1.5% of patients and was not
      associated with antibodies. Thus, after 1 year in this prospective trial,
      patients with HLA antibodies had graft failure at a significantly higher rate
      than those without antibodies.

PMID- 14962000
TI  - Transmission of donor melanoma to multiple organ transplant recipients.
AB  - Malignant melanoma represents the most common tumour responsible for donor
      derived post transplantation malignancies. We report the varied presentation and
      outcome of three graft recipients (two kidney and hepatic) who developed
      metastatic melanoma following cadaveric organ transplantation from a single
      multiorgan donor. Two of the recipients presented with symptomatic metastatic
      lesions and the third patient, despite being carefully monitored, developed
      evidence of metastatic cutaneous melanoma. Two of the patients died as a direct
      result of their melanomas. The recipients of corneal and cardiac grafts remain
      disease-free. We conclude that despite careful screening, donor-derived tumours
      remain a not uncommon clinical entity. The identification of a lesion in one
      recipient should prompt immediate examination and investigation of the remaining
      recipients of multiorgan donations.

PMID- 14962001
TI  - Successful renal transplantation in a patient with congenital generalized
      lipodystrophy: a case report.

PMID- 14962004
TI  - Arteriolar dilations induced by contraction of hamster cremaster muscle are
      dependent on changes in endothelial cell calcium.
AB  - Muscle contraction initiates microvascular arteriolar dilation in regions
      directly overlapping the active fibres but the cells (vascular smooth muscle
      cells, endothelial cells) responsible for producing the dilation and the
      underlying signalling mechanisms are unknown. AIMS: We tested the hypothesis that
      changes in endothelial cell calcium (Ca2+) are involved in this dilation.
      METHODS: Four to five muscle fibres lying approximately perpendicular to
      arterioles (maximum diameter approximately 40 microm) were stimulated (4 Hz, 4-20
      V, 0.4 ms duration) and observations were made at the site of muscle
      fibre/arteriole overlap. RESULTS: Chelation of endothelial cell Ca2+ (with BAPTA)
      abolished dilations to 120 s of muscle contraction (5.6 +/- 1.5 microm in
      controls vs. 0.51 +/- 1.2 microm with BAPTA, n = 6), indicating that changes in
      endothelial cell Ca2+ are required for the response. To determine the time frame
      of the Ca2+ signal, we monitored whole endothelial cell Ca2+ (with Fura-PE3)
      prior to and following either 120 (n = 13), 30 (n = 9) or 10 (n = 9) s of muscle
      contraction. In all instances, no changes in Ca2+ were observed despite typical
      dilator responses. CONCLUSIONS: These data indicate that (i) the initiation of
      muscle contraction-induced arteriolar dilations depends on a change in
      endothelial cell Ca2+, which must be a transient event that takes place
      early/during stimulation, and (ii) maintenance of the dilation after contraction
      occurs via mechanisms that are independent of changes in global Ca2+ within the
      cell.

PMID- 14962005
TI  - Ca2+-activated Cl- current reduces transmural electrical heterogeneity within the
      rabbit left ventricle.
AB  - OBJECTIVE: Various cationic membrane channels contribute to the heterogeneity of
      action potential configuration between the transmural layers of the left
      ventricle. The role of anionic membrane channels is less intensively studied. We
      investigated the role of the Ca2+-activated Cl- current, ICl(Ca), in transmural
      electrical heterogeneity. METHODS AND RESULTS: We determined the density of
      ICl(Ca) and its physiological role in subepicardial and subendocardial
      ventricular myocytes of rabbit using the patch-clamp technique. ICl(Ca) was
      measured as the 4,4'diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS)
      sensitive current. The current-voltage relationships and the densities of ICl(Ca)
      were similar in subepicardial and subendocardial myocytes. However, the
      functional role of ICl(Ca) exhibited striking differences. In subendocardial
      myocytes, blockade of ICl(Ca) by DIDS increased action potential duration (APD)
      significantly at all measured stimulus frequencies (3.33-0.2 Hz). In
      subepicardial myocytes, ICl(Ca) blockade increased APD only at 3.33 Hz, but not
      at the lower stimulus frequencies. At 1 Hz, ICl(Ca) blockade in subepicardial
      myocytes only caused an APD increase when the transient outward K+ current, Ito1,
      was blocked. CONCLUSIONS: The densities and gating properties of ICl(Ca) are
      similar in subepicardial and subendocardial myocytes. ICl(Ca) contributes to APD
      shortening in subendocardial, but not in subepicardial myocytes except at 3.33
      Hz. These differences in functional expression of ICl(Ca) reduce the electrical
      heterogeneity in rabbit left ventricle.

PMID- 14962006
TI  - Effect of knee flexion angle on active joint stiffness.
AB  - AIM: The purpose of this study was to determine if active joint stiffness
      measured during maximum voluntary knee extension contractions was affected by
      knee flexion angle. METHODS: Eighteen subjects volunteered (11 male, seven
      female). A stretch was imposed on isometric knee contractions performed at 30
      degrees, 50 degrees, 70 degrees, 90 degrees, and 110 degrees of knee flexion.
      Active joint stiffness was computed from the increase in torque relative to the
      change in knee flexion angle for the first 50 ms of the stretch (approximately
      1.5 degrees ) and corrected for effects of gravitational component due to leg
      mass and passive tension. RESULTS: There was a plateau in knee extension torque
      between 70 degrees and 90 degrees with lower values at all other angles (P <
      0.05). Peak active joint stiffness occurred at 70 degrees with lower values (P <
      0.05) at all other angles except 50 degrees. Stiffness at 70 degrees (441.1 +/-
      189.9 Nm rad-1) was 49% higher than at 30 degrees and 45% higher than at 110
      degrees. CONCLUSION: Active joint stiffness was dependent on knee flexion angle.
      Peak joint stiffness during maximal contractions occurred at, or prior to, the
      optimal angle for torque production for all subjects.

PMID- 14962007
TI  - Different hepatic vascular response to noradrenaline and histamine between guinea
      pig and rat.
AB  - AIM: Hepatic xenotransplantation from guinea-pig to rat has not been established.
      This failure is partly ascribed to differences in hepatic vascular
      characteristics between two species. However, the differences in hepatic vascular
      resistance distribution and responses to vasoconstrictors are not known. The
      present study was designed to determine basal levels of segmental vascular
      resistances and the responses to histamine and noradrenaline in isolated guinea
      pig and rat livers. METHODS: The livers were haemoperfused (Hct 8.3%) via the
      portal vein at a constant flow. The sinusoidal pressure was measured by the
      double occlusion pressure, and was used to determine the pre- (Rpre) and post
      sinusoidal (Rpost) resistances. RESULTS: There was no significant difference in
      basal total hepatic vascular resistance (Rt) between two species, whereas Rpre in
      rat (69% of Rt) was significantly greater than that in guinea-pig (61% of Rt).
      The responses to noradrenaline were similar; Rpre increased in a greater
      magnitude than Rpost, and liver weight was reduced. However, the noradrenaline
      induced increase in Rt was greater in rats than in guinea-pigs. In contrast,
      histamine increased predominantly Rpost over Rpre, and increased liver weight in
      guinea-pig, while it affected no haemodynamic variables in rat. CONCLUSION: There
      exist species differences in the hepatic vasculature between rat and guinea-pig.
      Basal pre-sinusoidal resistance in rat is greater than that in guinea-pig.
      Although noradrenaline predominantly contracts pre-sinusoidal vessels in both
      species, histamine causes predominant post-sinusoidal vasoconstriction in guinea
      pig liver, while it has no vasoactive effects on rat liver.

PMID- 14962008
TI  - Effects of fatigue on depolarization- and caffeine-induced contractures of
      skinned fibres.
AB  - AIMS: Fatigue has been shown to cause intrinsic alterations in sarcoplasmic
      reticulum (SR) Ca2+ release. METHODS: In this investigation, frog semitendinosus
      muscles were stimulated to fatigue, in vitro (80 Hz, 100 ms, 1 train s-1, 5 min).
      Immediately after stimulation, single fibres were removed and skinned using
      either chemically or mechanically skinning. Contralateral muscle were treated
      similarly but were not stimulated. RESULTS: In fatigued, saponin skinned fibres,
      contracture responses to low [caffeine] (4-8 mm) were depressed compared with
      control. However, responses to high concentrations (10-15 mm) were not different
      between conditions. In the fatigued, mechanically skinned fibres, responses to
      chloride depolarization were depressed at all [chloride] (20-100 mm) compared
      with control. CONCLUSIONS: These results suggest that fatigue causes intrinsic
      alterations in both the SR Ca2+ release channel as well as communication between
      the transverse-tubule and the SR.

PMID- 14962009
TI  - Clenbuterol treatment affects myosin heavy chain isoforms and MyoD content
      similarly in intact and regenerated soleus muscles.
AB  - AIMS: Pharmacological treatment with the beta2-adrenoceptor agonist clenbuterol
      is known to induce a slow-to-fast fibre type and myosin heavy chain (MHC) isoform
      transition in intact muscle. This study examined the sensitivity of regenerated
      soleus muscle to 4 weeks of clenbuterol treatment (2 mg kg-1 day-1). METHODS:
      Female Wistar rats were divided into two groups: vehicle treated (n = 8) and
      clenbuterol treated (n = 8). The clenbuterol effects on MHC and MyoD expression
      were examined in soleus muscles either intact, or previously degenerated by venom
      of the Notechis scutatus scutatus snake. RESULTS: Post-treatment body weights and
      skeletal muscle weights were not affected by clenbuterol treatment. Muscle
      protein concentration was higher, and body fat lower in clenbuterol-treated rats
      than in vehicle-treated animals (P < 0.05). Polyacrylamide gel electrophoresis of
      soleus myofibrillar protein indicated a clenbuterol-induced decrease in the
      relative percentage of type I MHC with a concomitant increase in type IIa MHC
      (31%, P < 0.001). No degeneration effect was observed after 28 days of recovery
      on the MHC isoform content, and regenerated soleus muscles exhibited the same
      phenotypical profile as intact soleus muscles, whether or not they were treated
      with clenbuterol. In intact and in regenerated soleus muscles, MyoD protein
      levels were significantly increased by clenbuterol treatment (90 and 77%,
      respectively, P < 0.001). CONCLUSION: These results show that regenerated soleus
      muscles, comprising a homogeneous population of fibres deriving from satellite
      cells, have a similar response to clenbuterol as intact muscle arising from at
      least two discrete populations of myotubes; it is suggested that the activity of
      signalling pathways involved in the effects of clenbuterol on MHC transitions is
      not related to the developmental history of myofibres.

PMID- 14962010
TI  - Localization of MyoD, myogenin and cell cycle regulatory factors in
      hypertrophying rat skeletal muscles.
AB  - AIM: MyoD, myogenin, proliferating cell nuclear antigen (PCNA) and cyclin
      dependent kinase inhibitor p21 (p21) proteins are key molecules in inducing the
      growth of myogenic cells in vitro. However, it has not been determined which cell
      types express these factors in hypertrophying skeletal muscles in vivo. METHODS:
      Using immunohistochemical techniques, we examined the spatial and temporal
      expression patterns of MyoD, myogenin, PCNA and p21 proteins in functionally
      overloaded rat plantaris muscles induced by ablation of the soleus and
      gastrocnemius muscles. RESULTS: MyoD and myogenin were detected in myonuclei
      located inside the dystrophin-positive plasma membrane of myofibres, m-cadherin
      positive satellite cell nuclei and nuclei located in the interstitial spaces
      between myofibres on days 1, 3, 5 and 7 post-surgery. Entry of satellite cells
      into the cell cycle was indicated by the expression of PCNA on day 3 post
      surgery, and withdrawal from the cell cycle was observed by the expression of p21
      in satellite cell nuclei on day 5 post-surgery. However, the expression of both
      PCNA and p21 in satellite cell nuclei disappeared on day 7 post-surgery.
      CONCLUSION: These results indicate that proliferated satellite cell-derived
      myoblasts and undefined myogenic cells located in the interstitial spaces may
      contribute to an increase in myonuclear number and/or hyperplasia. Furthermore,
      we provide evidence that all of myonuclei, satellite cells and undefined myogenic
      cells express both MyoD and myogenin proteins. These results suggest that
      continual expression of MyoD and myogenin proteins in these cells is an essential
      molecular event which induces the successful hypertrophy of skeletal muscles.

PMID- 14962011
TI  - Time course of capillary structure changes in rat skeletal muscle following
      strenuous eccentric exercise.
AB  - AIM: We examined the time course of capillary structure changes in rat skeletal
      muscle at 1, 3 and 7 days after strenuous eccentric exercise. METHODS: The right
      gastrocnemius muscles of anaesthetized male Wistar rats were subjected to 300
      controlled eccentric contractions using electrical stimulation. The contralateral
      gastrocnemius muscle was used as control. All morphometric parameters were
      determined in in situ perfused gastrocnemius muscles in red (Gr, predominantly
      slow-twitch fibre) and white (Gw, predominantly fast-twitch fibre) portions.
      RESULTS: Muscle fibre damage was evident on days 1, 3 and 7 in Gr (29.3-53.9%
      damaged fibres) and Gw (58.9-86.8% damaged fibres) of exercised legs. Electron
      micrographs of transverse sections did not display collapsed or obstructed
      capillaries in exercised legs, and capillary endothelial cells retained their
      normal structures. However, capillary luminal shapes and area were altered in
      exercised legs on days 1 and 3. The ratio between minimal and maximal capillary
      diameter in a transverse section (i.e. luminal ellipticity) significantly
      differed when comparing control (Gr, 0.75 +/- 0.02; Gw, 0.79 +/- 0.03) and
      exercised legs (Gr, 0.65 +/- 0.03; Gw, 0.66 +/- 0.04) at 1 day after exercise.
      The mean capillary luminal area was significantly increased in exercised legs
      after 1 day (Gw, +24.3%) and 3 days (Gr, +31.9%; Gw, +62.2%) compared with
      control. CONCLUSION: We conclude that (1) capillary endothelial cell structure
      was maintained in damaged muscles, (2) changes in capillary lumen shapes and
      distensibility occur in the degenerated muscle up to 3 days after the eccentric
      contraction period.

PMID- 14962012
TI  - Experimentally induced ischaemic pain in healthy humans is attenuated by the
      adenosine receptor antagonist theophylline.
AB  - AIMS: Endogenous adenosine is considered a prominent pain mediator in ischaemia.
      In contrast, it has been shown that exogenous adenosine can reduce tourniquet
      induced ischaemic pain in healthy volunteers. The aim of this study was to
      investigate if pharmacological antagonism of endogenous adenosine actions with an
      intravenous infusion of theophylline could attenuate experimentally induced
      ischaemic pain. METHODS: Nineteen healthy volunteers, 11 males, eight female,
      received theophylline 7 mg kg-1 or placebo intravenously, in a randomized, double
      blind and crossover fashion, prior to a sub-maximum effort forearm tourniquet
      test. Experiments were carried out with 1-week intervals to avoid pre
      conditioning. Pain scores [visual analogue scale (VAS), 0-100] were assessed
      every minute up to a maximum of 30 min. RESULTS: The sum of pain scores
      (accumulation of VAS scores) was attenuated by theophylline, 691 [200-1550
      (median and 25-75% percentiles)], compared with placebo, 1231 (545-1675), P <
      0.001. Also, peak VAS pain was lower during theophylline treatment, 48 +/- 38
      (mean +/- SD), compared with placebo, 74 +/- 27, P < 0.001. Blood pressure
      increased during the experiment with no difference between treatments. Heart rate
      was not affected by tourniquet or drug treatment. CONCLUSIONS: It is concluded
      that the adenosine receptor antagonist theophylline is able to attenuate the
      development of ischaemia pain during experimental ischaemia in humans. This
      implies a role for adenosine as both facilitatory mediator and a modulator of
      ischaemia skeletal muscle pain.

PMID- 14962013
TI  - Effects of N-nitro l-arginine methyl ester (l-NAME), a potent nitric oxide
      synthase inhibitor, on visual evoked potentials of rats exposed to different
      experimental stress models.
AB  - AIM: The aim of our study was to investigate the effects of the nitric oxide
      synthase inhibitor, N-nitro l-arginine methyl ester (l-NAME, 10 mg kg-1 day-1
      i.p.), on visual evoked potentials (VEPs) and lipid peroxidation expected to
      occur during chronic stress (15 days). METHODS: Eight experimental groups, each
      consisting of 10 rats, were formed: control group (C), the group injected with l
      NAME (L), groups exposed to cold stress (CS), immobilization stress (IS), and
      both cold and immobilization stress (CIS), groups exposed to stress and injected
      with l-NAME (CSL, ISL, CISL). RESULTS: l-NAME decreased brain and retina nitrite
      levels in all experimental groups compared with their corresponding control
      groups. l-NAME decreased glutathione peroxidase (GSH-Px) activity in the brain
      and retina in the L group, but increased it in the CSL and CISL groups compared
      with the C group. Lipid peroxidation was increased in the brain and retina
      tissues of all stress groups with respect to the C group. l-NAME markedly
      increased brain thiobarbituric acid reactive substances (TBARS) levels in the L
      group, while significantly decreasing brain and retina TBARS levels in all stress
      groups in comparison with their respective control groups. l-NAME caused a
      significant delay in all components of VEPs in the L group compared with the C
      group. However, l-NAME significantly decreased latencies of P1, N1, P2 and P3
      components in the CSL group and all components in the ISL and CISL groups with
      respect to their corresponding control groups. CONCLUSION: This study clearly
      indicated that lipid peroxidation may be one possible factor affecting VEP
      components.

PMID- 14962015
TI  - Ringing the changes: some resolutions for the new year and beyond.

PMID- 14962016
TI  - Developing effective, efficient and practical methods of assessing the
      professional skills of physicians in practice.

PMID- 14962017
TI  - Why are medical journals so badly written?

PMID- 14962018
TI  - Cheating.

PMID- 14962019
TI  - Board certification and physician quality.

PMID- 14962020
TI  - A model for GME: shifting from process to outcomes. A progress report from the
      Accreditation Council for Graduate Medical Education.

PMID- 14962021
TI  - Clinical fire drills and skill decay: can we develop an evidence base for policy
      and a language for training?

PMID- 14962022
TI  - Limiting the playing field: does restricting the number of possible diagnoses
      reduce errors due to diagnosis-specific feature identification?
AB  - INTRODUCTION: Diagnostic hypotheses influence the identification of clinical
      features by medical trainees. This influence is strong enough to lead students to
      interpret features incorrectly if the initial diagnostic suggestion is incorrect.
      In the present study, we investigated whether reducing the pool of possible
      diagnoses at the time of test to a few highly plausible alternatives would focus
      the search for and interpretation of clinical features on a few alternative
      diagnoses and, as a result, reduce the influence of an initial diagnostic
      hypothesis on feature identification. METHODS: Naive students were taught 10
      electrocardiographic (ECG) diagnoses. At test, they were asked to report all
      features visible on new ECGs. The test ECGs were presented with the suggestion of
      a tentative diagnosis (either the correct diagnosis or a plausible alternative)
      under 2 conditions: students were either instructed that the ECG represented one
      of 3 possible diagnoses (which were explicitly mentioned), or they were
      instructed that the ECG might represent any of the 10 diagnoses learned. RESULTS:
      Students' identification of the ECG features was strongly influenced by the
      diagnostic suggestion. Reducing the number of alternatives available at the time
      of test did not reduce the impact of a diagnostic suggestion on feature
      interpretation. DISCUSSION: Increasing the salience of alternative hypotheses
      does not reduce the impact of a diagnostic suggestion on the interpretation of
      clinical features.

PMID- 14962023
TI  - Degree of concurrency among experts in data collection and diagnostic hypothesis
      generation during clinical encounters.
AB  - BACKGROUND: Given that there are variations in clinicians' reasoning, methods to
      elaborate scoring checklists for standardised patient-based assessment need to be
      valid. The use of data elicited by experts solving problems independently has
      been advocated as a method of setting performance standards. AIMS: To determine
      the degree of concurrence and common characteristics among items independently
      elicited by doctors during patient encounters and to assess the number of experts
      needed to derive reliable performance standards. METHODS: Six experienced
      internists worked-up the same 7 chief complaints with standardised patients
      (SPs). A stimulated recall of the recorded encounter was then performed. The
      degree of concurrence of the collected history and physical examination
      information and the generated diagnostic hypotheses was computed. Reliability was
      derived from generalisability analyses. RESULTS: By case, experts elicited a mean
      of 114 information items (SD = 15) and generated 30 diagnostic hypotheses (SD =
      6). A high concurrence (80-100%) was observed for a mean of 22 information items
      (20%; SD = 6) and 7 diagnostic hypotheses (24%; SD = 2). More than a third of the
      153 highly concurrent information items were clarification questions. At least 3
      doctors were needed to obtain a reliability of 0.80 or higher when deriving the
      scoring checklists. CONCLUSION: The limited concurrency in data elicited by
      clinicians during a patient encounter supports the use of high-fidelity methods
      to develop performance checklists used in SP-based assessment. It also suggests
      that relying only on information collected to assess clinical competence may not
      be sufficient. Additional criteria, such as structure and style of work-up,
      should be further explored.

PMID- 14962024
TI  - Simulation in undergraduate medical education: bridging the gap between theory
      and practice.
AB  - OBJECTIVE: To evaluate the use of simulation-based teaching in the medical
      undergraduate curriculum in the context of management of medical emergencies,
      using a medium fidelity simulator. DESIGN: Small groups of medical students
      attended a simulation workshop on management of medical emergencies. The workshop
      was evaluated in a post-course questionnaire. SUBJECTS: All Year 4 medical
      students allocated to the resuscitation rotation during the first half of 2002.
      MAIN OUTCOME MEASURES: Student perceptions of learning outcomes, the value of the
      simulation in the undergraduate curriculum and their self-assessed improved
      mastery of workshop material. RESULTS: A total of 33 students attended the
      workshop and all completed questionnaires. Students rated the workshop highly and
      found it a valuable learning experience. In all, 21 (64%) students identified
      teamwork skills as key learning points; 11 (33%) felt they had learnt how to
      approach a problem better, particularly in terms of using a systematic approach,
      and 12 (36%) felt they had learnt how to apply their theoretical knowledge in a
      clinical setting better. All 33 students were positive about the use of
      simulation in their training; 14 students wrote that simulation should be used
      more or should be mandatory in training; 5 students commented positively on the
      realism of the learning experience and a further 5 said they valued the
      opportunity to learn new skills in a safe environment. CONCLUSION: This study
      demonstrates that medical students value simulation-based learning highly. In
      particular, they value the opportunity to apply their theoretical knowledge in a
      safe and realistic setting, to develop teamwork skills and to develop a
      systematic approach to a problem. A medium fidelity simulator is a valuable
      educational tool in medical undergraduate education.

PMID- 14962025
TI  - Assessing simulated patients in an educational setting: the MaSP (Maastricht
      Assessment of Simulated Patients).
AB  - CONTEXT: For more than two decades the Medical School in Maastricht, the
      Netherlands, has used simulated patients (SPs) to provide students with
      opportunities to practise their skills in communication and physical examination.
      In this educational setting a student meets a SP in a videotaped session.
      Feedback by the SP to the student at the end of the session is considered an
      important educational feature. We found no instruments to assess individual SP
      performance during those sessions. OBJECTIVE: To develop a valid, reliable and
      feasible instrument to evaluate the performance of SPs. METHODS: The content of
      the instrument was validated through interviews with students, teachers and
      experts who are involved with SPs. They were asked to indicate key features of
      good SP performance. Based on the interviews, a written checklist was developed
      to measure individual SP performance. The instrument was evaluated in a regular
      SP session at the medical school, involving 152 students and their teachers. MAIN
      OUTCOMES: All interviewees considered the scale to be satisfactory and the
      instrument to be valid. The feasibility and reliability of the checklists were
      investigated using the data of 398 returned checklists. Cronbach's alpha was
      found to be 0.73. Generalizability analysis showed that 12 completed checklists
      were required to obtain a reliable assessment of one SP. CONCLUSIONS: The
      Maastricht Assessment of Simulated Patients (MaSP) appears to be a valid,
      reliable and feasible tool to assess the performance of SPs in an educational
      setting.

PMID- 14962026
TI  - Crisis resource management training for an anaesthesia faculty: a new approach to
      continuing education.
AB  - BACKGROUND: Human error and system failures continue to play a substantial role
      in adverse outcomes in health care. Anaesthesia crisis resource management
      addresses many patient safety issues by teaching behavioural skills for critical
      events but it has not been systematically utilized to teach experienced faculty.
      METHODS: An anaesthesia crisis resource management course was created for the
      faculty of our medical school's anaesthesia teaching programmes. The course
      objectives were to understand and improve participants' proficiency in crisis
      resource management (CRM) skills and to learn skills for debriefing residents
      after critical events. Through surveys, measurement objectives assessed
      acceptance, utility and need for recurrent training immediately post-course.
      These were measured again approximately 1 year later along with self-perceived
      changes in the management of difficult or critical events. RESULTS: The highly
      rated course was well received in terms of overall course quality, realism,
      debriefings and didactic presentation. Course usefulness, CRM principles,
      debriefing skills and communication were highly rated immediately post-course and
      1 year later. Approximately half of the faculty staff reported a difficult or
      critical event following the course; of nine self-reported CRM performance
      criteria surveyed all claimed improvement in their CRM non-technical skills.
      CONCLUSIONS: A unique and highly rated anaesthesia faculty course was created;
      participation made the faculty staff eligible for malpractice premium reductions.
      Self-reported CRM behaviours in participants' most significant difficult or
      critical events indicated an improvement in performance. These data provide
      indirect evidence supporting the contention that this type of training should be
      more widely promoted, although more definitive measures of improved outcomes are
      needed.

PMID- 14962027
TI  - Making patient safety the focus: crisis resource management in the undergraduate
      curriculum.
AB  - BACKGROUND: This paper examines the role of high fidelity simulation and crisis
      resource management in bridging the gap between theory and practice. Patient
      safety is fundamental to healthcare professional practice and is a common goal
      for healthcare providers. It provides a focus to motivate practitioners. Patient
      safety issues are not a priority in undergraduate curricula. Raising the profile
      at this level is crucial to improving the safety and quality of healthcare
      delivery. This paper explores the role of simulation in providing a realistic,
      safe environment for participants with different levels of experience to manage
      evolving crises in the context of their work environment. METHODS: The Southern
      Health Simulation and Skills Centre uses a patient safety focus in delivering a
      specialised educational programme adapted from aviation to healthcare. The
      programme, crisis resource management, enables participants to consolidate
      knowledge, attitudes and skills to achieve a deeper understanding of how their
      performance impacts on patient safety and the quality of healthcare provided.
      Self-reported written evaluation data was collected from participants of three
      different courses at Southern Health. RESULTS: Participants consistently report
      that these courses offer unique learning experiences that address aspects of
      workplace learning in ways that have not previously been possible. A video
      assisted reflective process powerfully reinforces learning. CONCLUSION: Crisis
      resource management courses demonstrate the value of simulation in bridging the
      gap between 'knowing' and 'doing' and keeping the focus on patient safety.
      Recommendations are made for ways in which the core elements of crisis resource
      management philosophy can influence the conceptualization of a new medical
      curriculum.

PMID- 14962028
TI  - Exit learning outcomes for the PRHO year: an evidence base for informed
      decisions.
AB  - OBJECTIVE: To evaluate potential learning outcomes for pre-registration house
      officer (PRHO) training and develop an evidence base for informed decision
      making. DESIGN AND SETTING: A 2-stage Delphi process was employed to establish
      the opinions of Scottish stakeholders with regard to learning outcomes for the
      PRHO year. PARTICIPANTS: Doctors involved in the provision of PRHO training,
      including deans, postgraduate tutors and general practitioners (GPs) with
      trainees, were invited to participate in the study. MAIN OUTCOME MEASURES:
      Respondents rated a range of outcomes according to which they believed should be
      included or excluded from the PRHO training year. RESULTS: Learning outcomes
      identified for PRHOs were grouped under the 12-domain framework of the 3-circle
      model: 'What the doctor can do', 'How they approach their practice' and 'Their
      professionalism'. Based on the consensus opinions gained in the Delphi study, the
      ratings were classified into priority groupings. Priority 1 contained 45 of the
      original 81 learning outcomes, representing each area of the 3-circle model, with
      emphasis on the domains of clinical skills, patient investigation/management,
      communication, appropriate attitudes and personal development. Health promotion
      and disease prevention was the only domain not represented at priority 1.
      Priority 2 contained 24 outcomes with emphasis on the understanding of clinical
      skills, patient management and personal development. Priority 3 contained 12
      outcomes indicating a lack of emphasis for some outcomes, particularly the role
      of the doctor and health promotion. CONCLUSION: Consensus on the learning
      outcomes for PRHO training has been achieved, providing an evidence base for
      curriculum planning. The relative priority assigned to these outcomes can
      facilitate the use of the evidence. This evidence base should be referred to when
      reviewing any PRHO training programme.

PMID- 14962029
TI  - Teaching research methodology in medical schools: students' attitudes towards and
      knowledge about science.
AB  - OBJECTIVE: To explore the relationship between teaching scientific methodology in
      Year 2 of the medical curriculum and student attitudes towards and knowledge
      about science and scientific methodology. DESIGN: Anonymous questionnaire survey
      developed for this purpose. SETTING: Zagreb University School of Medicine,
      Croatia. PARTICIPANTS: A total of 932 students (response rate 58%) from all 6
      years were invited to participate. MAIN OUTCOME MEASURES: Score on attitude scale
      with 45 Likert-type statements and score on knowledge test consisting of 8
      multiple choice questions. RESULTS: The average attitude score for all students
      was 166 +/- 22 out of a maximum of 225, indicating a positive attitude towards
      science and scientific research. The students' average score on the knowledge
      test was 3.2 +/- 1.7 on 8 questions. Students who had finished Year 2 had the
      highest mean attitude (173 +/- 24) and knowledge (4.7 +/- 1.7) scores compared
      with other year groups (P < 0.001, anova and Tukey posthoc test). For students
      who had attended a mandatory Year 2 course on the principles of scientific
      research in medicine (Years 3 to 6), multiple linear regression analysis showed
      that knowledge test score (B = 3.4; SE = 0.4; 95% confidence interval 2.5-4.2; P
      < 0.001) and average grades (B = 7.6; SE = 1.5; 95% CI 4.6-10.6; P < 0.001) were
      significant predictors of attitude towards science, but not sex or failure to
      pass a year (B = - 0.6; SE = 1.7; 95% CI - 3.9-2.6; P = 0.707; and B = - 3.1; SE
      = 1.9; 95% CI - 6.8-5.7; P = 0.097, respectively). CONCLUSION: Medical students
      have generally positive attitudes towards science and scientific research in
      medicine. Attendance of a course on research methodology is related to a positive
      attitude towards science.

PMID- 14962030
TI  - Portfolio use in general practice vocational training: a survey of GP registrars.
AB  - BACKGROUND: Portfolios are increasingly advocated in medical education.
      Qualitative studies have suggested their value in stimulating experiential
      learning, promoting deep learning and encouraging reflection. This study explored
      the use of educational portfolios in reflective learning by general practice (GP)
      registrars in Yorkshire, England. METHOD: A postal questionnaire was sent to the
      92 registrars of a deanery in November 2001, after a pilot study with registrars
      in a single district had been carried out. The questionnaire explored the
      registrars' use of the portfolio to collect information and for reflection, as
      well as registrars' attitudes towards the portfolio. It was returned by 71
      registrars, representing a 77% response rate. Structured in-depth interviews were
      used to support the results obtained. RESULTS: Of the registrars who responded,
      65% recorded information on a regular basis and 42% used the portfolio in
      reflective learning. Experienced registrars used the portfolio least. Those with
      supportive trainers used the portfolio more in reflection. CONCLUSIONS: The study
      suggests that the role of the trainer/supervisor is vital in portfolio-based
      learning. It raises questions about the acceptability of portfolio learning. It
      adds weight to the suggestion that careful introduction of portfolios and
      training of supervisors is vital. Further work to establish the role of
      portfolios in reflective learning is recommended.

PMID- 14962031
TI  - How international is Medical Education?
AB  - AIMS: To consider Medical Education's claim to international status in terms of
      the extent of international authorship within published articles, the degree to
      which authors draw on the international literature to support their work, and its
      self-citation rates and publication decisions. METHOD: We examined 6 journals'
      citation rates for the period 1997-2001 to see if there was evidence of national
      publication bias; we calculated their self-citation rates to see if this had any
      influence on impact factor, and we examined Medical Education's management files
      for trends which might indicate publication bias due to country of origin of
      authors. RESULTS: All 6 journals exhibited a bias in favour of citing journals
      from their own countries. The US journals were more likely to cite journals from
      their own country. Medical Education was most likely to cite journals from non-UK
      countries. Self-citation rates did not appear to affect impact factors. The ratio
      of UK to non-UK papers published in Medical Education has not changed
      significantly over the period studied although non-UK submissions increased
      sharply in 2002 and the number of North American submissions has doubled since
      1998. CONCLUSION: Medical Education is justified in calling itself an
      international journal to the extent that the majority of papers it publishes are
      from countries other than the UK, and it is more likely than other journals in
      the field to publish papers which cite work in journals published outside the UK.
      Nevertheless, there is some evidence of publication bias in the journal and more
      work is needed to discover why this is the case. Various strategies to address
      the issue of national bias in Medical Education are discussed.

PMID- 14962035
TI  - Guessing in selected-response tests.

PMID- 14962037
TI  - A comparison of the traditional method of counting viable cells and a quick
      microplate method for monitoring the growth characteristics of Listeria
      monocytogenes.
AB  - AIMS: To determine: (i) the growth parameters (specific growth rate, lag time,
      asymptotic amount of growth, generation time and time for maximum growth rate) of
      Listeria monocytogenes in different broths by standard cultivation methods and
      (ii) whether a microplate method in conjunction with a standard nondedicated
      plate reader could be adapted to routine assay. METHODS AND RESULTS: Growth
      curves were determined from cell numbers in a standard tube method at 2 h
      intervals by serial dilution and plating, and in a microplate method by
      absorbance measurements. Growth curves were fitted with a modified Gompertz
      function. CONCLUSIONS: The microplate method was similar to the standard
      cultivation methods in accuracy, required less chemical reagents, and
      considerably reduced the time required for analyses. This work also illustrates
      that growth characteristics of bacteria are not necessarily constant, and depend
      on the methodology used. SIGNIFICANCE AND IMPACT OF THE STUDY: It is not the
      intended purpose of this paper to present all the data for the media tested but
      instead to illustrate the success of the microplate method for studying growth
      kinetics compared to a standard cultivation method and system precision. The
      method will be of considerable benefit to laboratories unable to afford dedicated
      workstations.

PMID- 14962038
TI  - Liquid culture carbon, nitrogen and inorganic phosphate source regulate
      nematicidal activity by fluorescent pseudomonads in vitro.
AB  - AIMS: The aim of the present investigation was to determine the influence of
      nutrients on the nematicidal activity by Pseudomonas aeruginosa strain IE-6S+ and
      Ps. fluorescens strain CHA0 in vitro. METHODS AND RESULTS: Culture filtrate of IE
      6S+ and CHA0 obtained from chemically defined medium caused mortality of
      Meloidogyne javanica juveniles in vitro and that growth medium amended with
      various C, N or inorganic phosphate (Pi) sources markedly influenced nematicidal
      activity of the two bacteria. Glycerol (C source), propionate (fatty acid
      precursor) and L-lysine (N source) enhanced nematicidal activity while glucose
      (C), L-valine (N) and Pi substantially repressed nematicidal activity of the two
      bacteria. CONCLUSION: Liquid culture amendments with various C, N or Pi sources
      modulate the biosynthesis of nematicidal agents to a different extent in vitro.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Developing bacterial strains more
      responsive to certain environmental signals can be exploited for increased
      secondary metabolite production in pharmaceutical fermentations and offers new
      avenues to improve biocontrol.

PMID- 14962039
TI  - A simple and reliable method for rapid production and purification of Pseudomonas
      aeruginosa haemolytic phospholipase C.
AB  - AIMS: To design a simple method to produce active recombinant Pseudomonas
      aeruginosa haemolytic phospholipase C (PLC). METHOD AND RESULTS: Pseudomonas
      aeruginosa PLC is a virulence factor mainly involved in inflammatory and
      cytotoxic responses. While ammonium sulphate purification requires large amounts
      of bacterial suspensions and leads to low yields, production of recombinant
      protein in Escherichia coli is no more successful because of frequent inclusion
      bodies and accumulation of inactive PLC in the periplasmic space. Using an
      inducible system based on the glucose-repressed inv1 promoter in the yeast
      Schizosaccharomyces pombe, we were able to produce up to 10 IU ml(-1) of pure
      toxin within 24 h. CONCLUSIONS: This work describes the first method to easily
      get recombinant haemolytic PLC. SIGNIFICANCE AND IMPACT OF THE STUDY: This method
      provides a powerful tool to study the mechanisms leading to its cellular
      toxicity.

PMID- 14962040
TI  - In vivo characterization of Lactobacillus johnsonii FI9785 for use as a defined
      competitive exclusion agent against bacterial pathogens in poultry.
AB  - AIMS: To test the efficacy of Lactobacillus johnsonii FI9785 in reducing the
      colonization and shedding of Salmonella enterica serotype Enteritidis,
      Escherichia coli O78:K80 and Clostridium perfringens in poultry. METHODS AND
      RESULTS: Specific pathogen-free chicks (1 day old) were dosed with a single oral
      inoculum of 1x10(9) CFU. Lactobacillus johnsonii FI9785 and 24 h later were
      challenged in separate experiments with S. Enteritidis (S1400, nalr) and E. coli
      O78:K80 (EC34195, nalr). There were no significant effects against S. Enteritidis
      whereas colonization of the small intestine by E. coli O78:K80 was reduced
      significantly. Both S. Enteritidis and E. coli colonized the caeca and colon to
      levels equivalent to control birds and there was no reduction in shedding as
      assessed by a semi-quantitative cloacal swabbing technique. Specific pathogen
      free chicks (20 day old) were dosed with a single oral inoculum of 1x10(9) CFU L.
      johnsonii FI9785 and 24 h later were challenged with C. perfringens. A single
      oral dose of L. johnsonii FI9785 was sufficient to suppress all aspects of
      colonization and persistence of C. perfringens. CONCLUSIONS: Lactobacillus
      johnsonii FI9785 may be given to poultry for use as a competitive exclusion agent
      to control C. perfringens. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus
      johnsonii FI9785 may be a valuable tool to control the endemic disease of
      necrotic enteritis, thereby reducing economic losses associated with reduced use
      of antimicrobials in the poultry industry.

PMID- 14962041
TI  - Use of folic acid casei medium reveals trimethoprim susceptibility of
      Lactobacillus species.
AB  - AIM: Lactobacilli have been reported to have intrinsic resistance to
      trimethoprim. The susceptibility of lactobacilli to trimethoprim on different
      media was investigated in order to search for a phenotypic test method that could
      indicate the presence of acquired resistance genes. METHODS AND RESULTS: Strains
      of Lactobacillus acidophilus, Lact. paracasei, Lact. rhamnosus and Lact.
      plantarum were susceptibility tested with E-tests on folic acid casei medium
      (FACM), MRS and defined medium 1. The effects of addition or removal of
      nucleosides and thymidine phosphorylase were investigated. E-tests on FACM
      yielded reproducible minimal inhibitory concentrations (MICs) for trimethoprim
      but addition of nucleosides was necessary for growth of Lact. acidophilus. MICs
      for the tested strains were 0.125-0.19, 0.25-3 and 0.064-0.19 microg ml(-1) for
      Lact. paracasei, Lact. rhamnosus and Lact. plantarum, respectively. With the
      addition of deoxyuridine and deoxyadenosine to FACM the MICs of Lact. acidophilus
      were 0.064-1 microg ml(-1). CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY:
      Lactobacilli do not have intrinsic resistance to trimethoprim. The results show
      that trimethoprim susceptibility testing of the tested Lactobacillus species is
      possible and indicate that transferable resistance genes are absent in all the
      tested strains.

PMID- 14962042
TI  - Minimizing prion risk without compromising the microbial composition of biofilms
      grown in vivo in a human plaque model.
AB  - AIMS: To determine whether the stringency of sterilization procedures for
      biological components of in vivo dental plaque-generating devices based on enamel
      can be increased to minimize prion risk without compromising natural biofilm
      composition. METHODS AND RESULTS: The composition of in vitro biofilms, grown on
      hypochlorite-treated and untreated autoclaved enamel surfaces, was determined
      using culture-based methods and checkerboard DNA: DNA hybridization analysis. No
      differences were found between biofilms recovered from either substrate.
      SIGNIFICANCE: Several in situ models allow generation of plaque in the oral
      cavity, followed by recovery of intact biofilms for experimentation. Approaches
      allowing plaque formation on natural tooth surfaces are most valuable, but
      present a possible infection risk to volunteers wearing plaque-collecting
      devices, particularly with respect to prions. Hypochlorite treatment of
      biological material, as an adjunct to autoclaving, reduces infection risk without
      compromising biofilm composition and should be adopted in all future studies
      using plaque-generating devices incorporating enamel, where there is a potential
      prion threat, and further investigated in other biological hard tissues.

PMID- 14962043
TI  - Detection and identification by real time PCR/RFLP analyses of Cryptosporidium
      species from human faeces.
AB  - AIMS: To detect a wide range of Cryptosporidium species from human faeces by
      analysis of the Cryptosporidium oocyst wall protein gene by PCR. METHODS AND
      RESULTS: The nested-assay comprised an initial amplification using a conventional
      thermocycler followed by real time PCR using a LightCycler with SYBR Green I for
      the characterization of the amplicons. The technique uses four sets of primers
      composed of five to six oligonucleotides with one to six base differences
      corresponding to the inter-species sequence differences of the gene fragment.
      Restriction fragment length polymorphism analysis identified Cryptosporidium
      hominis and C. parvum. The assay was evaluated using DNA extracted from purified
      material and faecal specimens containing a range of potential pathogens
      (including Cryptosporidium). The assay was specific, sensitive, reproducible and
      rapid. CONCLUSIONS: This unique technique enables the rapid detection of a range
      of polymorphic COWP gene sequences directly from faeces using real time PCR.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates a novel approach to
      identification of Cryptosporidium species and the identification of C. hominis
      and C. parvum. The technique may be especially useful for the analysis of
      environmental samples which are likely to contain heterogeneous mixtures of
      Cryptosporidium species.

PMID- 14962044
TI  - Structural features and hypoglycaemic activity of an exopolysaccharide produced
      by Sorangium cellulosum.
AB  - AIMS: To investigate the structural features and hypoglycaemic activity of an
      exopolysaccharide (EPS) produced by Sorangium cellulosum NUST06. METHODS AND
      RESULTS: The chemical structure of the EPS from S. cellulosum NUST06 was
      determined by gas-liquid chromatography, gas chromatography (GC), GC-mass
      spectrometry and nuclear magnetic resonance. The EPS was composed of a beta-D-(1-
      >4)-glucose backbone with alpha-D-(1-->6)-mannose side chains. The molecular
      weight of the EPS was approx. 2x10(5) Da. Healthy and alloxan-induced diabetic
      mice were used in the study. Blood glucose levels of the experimental animals
      during the trial period were analysed by a glucose test kit based on the glucose
      oxidase method. When 100 and 200 mg kg(-1) day(-1) of purified EPS was orally
      administered for 7 days, the serum glucose in alloxan-induced diabetic mice was
      reduced by 35.9 and 41.4% (P<0.01), and the serum glucose in healthy mice was
      reduced by 27.3 and 30.1% (P<0.05), respectively. CONCLUSIONS: The EPS produced
      by S. cellulosum NUST06 decreased blood glucose levels distinctly in both healthy
      and alloxan-induced diabetic mice. SIGNIFICANCE AND IMPACT OF THE STUDY: To
      elucidated the chemical structure of the EPS from S. cellulosum NUST06 and
      exploited the anti-diabetic potential of the EPS.

PMID- 14962045
TI  - Evaluation of the rrn operon copy number in Bifidobacterium using real-time PCR.
AB  - AIMS: A real-time PCR-based method was developed to evaluate the Bifidobacterium
      rRNA operon copy number. As a result of their repetitive nature, rRNA operons are
      very suitable targets for chromosomal integration of heterologous genes. METHODS
      AND RESULTS: The rrn operon multiplicity per chromosome was determined by real
      time PCR quantification of the 16S rRNA amplicons obtained from genomic DNA. The
      values obtained in several bifidobacterial strains of human origin ranged from 1
      to 5. The reliability of the method developed was confirmed by Southern
      hybridization technique. CONCLUSIONS: In the Bifidobacterium genus the rrn operon
      copies showed variability at species and strain level. The identification of
      Bifidobacterium strains with high rRNA multiplicity allowed the selection of
      potential hosts for chromosomal integration. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The methodology here proposed represents a rapid, reliable and sensitive
      new tool for the quantification of rrn operon copy number in bacteria.

PMID- 14962046
TI  - The glucose oxidase of Penicillium variabile P16: gene cloning, sequencing and
      expression.
AB  - AIMS: Isolation and characterization of the glucose oxidase (GOX)-encoding gene
      from a Penicillium variabile strain (P16) having a high level of GOX activity and
      comparison of its expression with that of another strain of P. variabile (NRRL
      1048) characterized by low GOX activity. METHODS AND RESULTS: The gene, isolated
      by PCR consisted of 1818 bp encoding 605 amino acid residues. Gene expression was
      analysed by Northern blotting and compared with that of P. variabile NRRL 1048.
      The higher GOX activity of strain P16 appeared likely because of de novo mRNA
      synthesis. Southern blotting analyses of the genomic DNA showed that the
      hybridization pattern of the two strains differed for the size of hybridizing
      fragment detected by the probe and slightly for their signal intensity.
      CONCLUSIONS: The GOX-encoding gene of P. variabile P16 was isolated and
      characterized to identify the molecular bases of its high level of expression and
      in view of improving enzyme production by developing a process based on
      heterologous expression. SIGNIFICANCE AND IMPACT OF THE STUDY: GOX-encoding genes
      can be subjected to high difference in their expression levels. The P16 strain of
      P. variable producing large amount of GOX as well as its encoding gene might be
      exploited for industrial applications.

PMID- 14962047
TI  - Rapid identification and differentiation of Saccharomyces cerevisiae,
      Saccharomyces bayanus and their hybrids by multiplex PCR.
AB  - AIMS: To develop a multiplex PCR assay for the specific identification and
      differentiation of Saccharomyces cerevisiae, S. bayanus and their hybrids.
      METHODS AND RESULTS: Two sets of primers with sequences complementary to the
      region YBR033w were used. A single amplicon of 1710 bp or 329 bp was obtained
      with species S. cerevisiae and S. bayanus, respectively, while the presence of
      both bands was observed in S. pastorianus because of its hybrid nature. Both
      amplification products were also obtained after amplification from DNA of several
      laboratory S. cerevisiae x S. bayanus hybrid strains. CONCLUSIONS: Multiplex PCR
      was optimized for the rapid and reliable identification of S. cerevisiae, S.
      bayanus and their hybrids. SIGNIFICANCE AND IMPACT OF THE STUDY: The procedure
      may be used for routine detection of the most common Saccharomyces sensu stricto
      yeasts involved in industrial fermentation processes, overcoming the problems of
      conventional techniques.

PMID- 14962048
TI  - Morphological and physiological changes of Staphylococcus aureus exposed to
      hypochlorous acid.
AB  - AIMS: To characterize hypochlorous acid (HOCl) stress resistance of
      Staphylococcus aureus and to assess physiological state and changes in cell
      morphology. METHODS AND RESULTS: Clinical wild-type strain of S. aureus was used
      in the stress with HOCl at concentrations ranging from 0 to 4 mg l(-1).
      Concentrations below 1.5 mg l(-1) caused no significant drop in viability. During
      2 h of HOCl stress at 2 mg l(-1), there was appearance of minicells capable of
      passing through the 0.45 microm pores of filtration membranes. Intracellular
      proteins increased gradually to reach a level of 51% of dry weight and an
      enhanced synthesis of at least two proteins of 23 and 220 kDa was concluded.
      CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: Staphylococcus aureus can
      undergo morphological and physiological changes during 2 h of exposure to 2 mg l(
      1) of HOCl, which represents an adaptative response towards the hypochlorous acid
      stress. This evolution limits the use of 0.45 microm pores size membrane filters
      for research on S. aureus in waters and the clinical environment.

PMID- 14962050
TI  - A detailed assessment of the pattern of moxidectin tissue distribution after pour
      on treatment in calves.
AB  - The use of topical (pour-on) administration of endectocide drugs in cattle has
      reached world-wide acceptance. However, only limited information is available on
      the kinetic behaviour for topically administered moxidectin (MXD). To improve our
      understanding of the relationship between pharmacokinetics and efficacy for pour
      on preparations, MXD concentration profiles were measured in tissues of endo- and
      ectoparasites location over 35 days postadministration. MXD distribution to the
      fluid content and mucosal tissue of the abomasum and different intestinal
      sections (duodenum, ileum, caecum and colon) was assessed. The comparative
      patterns of MXD distribution to skin and hypodermic tissue from different
      anatomical sites (backline, rib cage, thigh and face) were also investigated
      following the pour-on administration. Wide tissue distribution and long residence
      time characterized the kinetics of topically administered MXD. MXD was recovered
      between 1 and 35 days post-treatment in all the tissues investigated. The highest
      MXD availabilities were observed in the skin layers at the site of administration
      (backline) and in the fat tissue. The fluid contents of different intestinal
      sections showed MXD concentrations higher than those measured in their respective
      mucosal tissues, particularly at day 1 post-treatment. MXD concentrations in the
      skin (epidermis + dermis) were higher than those measured in the hypodermic
      tissue. Large differences in the availability of MXD in skin from different
      anatomical regions (backline > rib cage > thigh > face) were observed. The low
      plasma and the high skin availability indicate the formation of a skin depot of
      the drug, being released slowly to the plasma and reaching concentrations in
      systemic tissues (abomasal mucosa, lungs, etc.) similar to those measured after
      subcutaneous administration. These findings demonstrate that target parasites may
      be exposed to markedly different drug concentrations according to their location
      sites, which is particularly relevant for ectoparasites located in different
      anatomical regions. Knowledge of the tissue distribution of topically
      administered endectocides contributes to understand the differences observed in
      efficacy and/or persistence of activity and to optimize their use in cattle.

PMID- 14962051
TI  - Intramuscular dosing strategy for ampicillin sodium in horses, based on its
      distribution into tissue chambers before and after induction of inflammation.
AB  - The Pharmacokinetics (PK) and distribution into tissue chamber fluid (TCF) of
      intramuscularly (i.m.) administered ampicillin sodium were examined in horses in
      order to design adequate dosing strategies. Concentration-time curves of
      ampicillin in plasma and TCF were determined in six horses following
      administration of 15 mg/kg ampicillin sodium, before and after the induction of
      local inflammation with 0.5% carrageenan. The calculated parameters were used to
      simulate various dosage-dosing interval combinations. Ampicillin was absorbed
      very rapidly following i.m. administration. Plasma concentrations were maximual
      between 18 and 21 min after administration. None of the plasma PK parameters were
      affected significantly by local (TC) inflammation. Penetration of ampicillin into
      and elimination from the TCF were affected significantly by inflammation and the
      half-life of elimination from the tissue fluid t1/2(d) was significantly shorter
      in inflammation. In the simulated dosage-dosing interval scenarios, only a dosage
      of 15 mg ampicillin/kg four times daily would successfully treat all ampicillin
      susceptible bacterial isolates in well vascularized tissues. However a dosage as
      low as 10 mg/kg twice daily, would, in theory, treat all ampicillin-susceptible
      isolates in the inflamed poorly vascularized tissues. Decreasing the dosage
      results in loss of efficacy that cannot be completely compensated for by
      increasing the frequency of dosing.

PMID- 14962052
TI  - In vitro effects of cisapride, metoclopramide and bethanechol on smooth muscle
      preparations from abomasal antrum and duodenum of dairy cows.
AB  - The objective of this study was to investigate the effects of cisapride (CIS),
      metoclopramide (MET) and bethanechol (BET) on contractility parameters from
      smooth muscle preparations of the abomasal antrum and proximal duodenum of cows.
      Smooth muscle preparations were harvested shortly post-mortem from 42 healthy
      dairy cows, and concentration-response curves were performed by cumulative
      application of the drugs. Cisapride and MET did not have any significant effect
      on the contractility parameters studied, while BET induced a significant,
      concentration-dependent increase in basal tone (BT), mean amplitude (Amean), and
      area under the curve (AUC) in smooth muscle preparations from the abomasal
      antrum, but not from the duodenum. The effect of BET on BT was more pronounced in
      specimens with longitudinal orientation while the maximal obtainable effect (Vm)
      in Amean was more pronounced in circular-oriented preparations. Atropine (1 x 10
      5 m) significantly inhibited the effect of BET, whereas pre-incubation with
      hexamethonium or tetrodotoxin (TTX) had no effect, suggesting that the effect was
      mediated by cholinergic receptors on the smooth muscle. The results may be
      relevant to diseases or disorders associated with gastric emptying and gastric
      hypomotility. Further investigations are warranted to investigate the potential
      ability of BET to enhance abomasal emptying of adult dairy cows.

PMID- 14962053
TI  - Metabolism and residue depletion of albendazole and its metabolites in rainbow
      trout, tilapia and Atlantic salmon after oral administration.
AB  - Metabolic and residue depletion profiles of albendazole (ABZ) and its major
      metabolites in three fish species, rainbow trout, tilapia and Atlantic salmon are
      reported. Based on these profiles, similarities (or dissimilarities) between
      species will determine the potential to group fish species. ABZ at 10 mg/kg body
      weight was incorporated into fish food formulated in a gelatin base or in gel
      capsule and fed as a single dose to six fish from each species. Rainbow trout
      were held three each in a partitioned 600-L tank. Tilapia and Atlantic salmon
      were housed in separate 20-L tanks. Samples of muscle with adhering skin were
      collected at 8, 12, 18, 24, 48, 72, and 96 h postdose from trout kept at 12
      degrees C, at 4, 8, 12, 24, 48, 72, 96, 120, and 144 h postdose from tilapia kept
      at 25 degrees C and at 8, 14, 24, 48, 72, and 96 h postdose from Atlantic salmon
      kept at 15 degrees C. The samples were homogenized in dry ice and subjected to
      extraction and cleanup procedures. The final extracts were analyzed for parent
      drug ABZ and its major metabolites, albendazole sulfoxide (ABZ-SO), albendazole
      sulfone (ABZ-SO2) and albendazole aminosulfone using high-performance liquid
      chromatography with fluorescence detection. ABZ was depleted by 24 h in trout and
      tilapia and by 48 h in salmon; ABZ-SO, a pharmacologically active metabolite, was
      depleted by 48 h in tilapia, by 72 h in rainbow trout and was present until 96 h
      in salmon; and low levels of ABZ-SO2 and albendazole aminosulfone, both inactive
      metabolites, were detectable at least till 96 h in all three fish species.

PMID- 14962054
TI  - Detection and quantification of cocaine metabolites in urine samples from horses
      administered cocaine.
AB  - Cocaine is a naturally occurring alkaloid that is commonly abused by human-beings
      for its psychostimulatory effects. Occasionally, very small concentrations (i.e.
      <100 ng/mL) of the primary cocaine metabolite, benzoylecgonine (BZE) have been
      detected in urine collected from horses competing in athletic events. In this
      study urine samples, collected from four horses following the administration of
      2.5 and 20 mg of cocaine sublingually and 50 mg of cocaine intravenously, were
      analyzed for the presence of cocaine and/or its metabolites by enzyme-linked
      immunosorbent assay (ELISA) and gas chromatography-mass spectrometry (GC-MS). The
      results of ELISA analysis of urine samples collected from all four horses
      suggested the presence of cocaine and/or its metabolites up to 10, 48, and 72 h
      after administration of 2.5, 20, and 50 mg of cocaine, respectively. The results
      of GC-MS analysis confirmed the presence of BZE above the limit of quantification
      (LOQ = 5 ng/mL) in urine samples collected from all four horses for up to 24 h
      after administration of 2.5 mg of cocaine and for up to 48 h after administration
      of 20 and 50 mg of cocaine. No obvious behavioral effects or overt alterations of
      heart rate or rhythm were noted in any of these horses after cocaine
      administration.

PMID- 14962055
TI  - Role of prostaglandins in the development of hyperthermia in heat-stressed,
      lactating Holstein cows.

PMID- 14962056
TI  - Evaluation of adverse effects of EMLA (lidocaine/prilocaine) cream for the
      placement of jugular catheters in healthy cats.

PMID- 14962057
TI  - Melatonin and viral infections.
AB  - The therapeutic effects of melatonin against viral infections, with emphasis on
      the Venezuelan equine encephalomyelitis (VEE), are reviewed. Melatonin has been
      shown to prevent paralysis and death in mice infected with the
      encephalomyocarditis virus and to decrease viremia. Melatonin also postpones the
      onset of the disease produced by Semliki Forest virus inoculation and reduces the
      mortality of West Nile virus-infected mice stressed by either isolation or
      dexamethasone injection. An increase in the host resistance to the virus via a
      peripheral immunostimulatory activity is considered responsible for these
      effects. It has also been demonstrated that melatonin protects some strains of
      mink against Aleutian disease, and prevents the reduction of B- and T-cells as
      well as Th1 cytokine secretion in mice infected with leukemia retrovirus. In VEE
      infected mice, melatonin postpones the onset of the disease and death for several
      days and reduces the mortality rate. This protective effect seems to be due to
      the increase in the production of interleukin-1beta (IL-1beta), as 100% of the
      infected mice treated with melatonin die when IL-1beta is blocked with antimurine
      IL-1beta antibodies. Although melatonin administration raises serum levels of
      tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), the
      mortality observed in neutralization experiments with the corresponding
      anticytokine antibodies, suggests that neither TNF-alpha nor IFN-gamma are
      essential for the protective effect of melatonin on murine VEE virus infection.
      Melatonin treatment also enhances the efficiency of immunization against the VEE
      virus. Reactive oxygen species have been implicated in the dissemination of this
      virus, and their deleterious effects may be diminished by melatonin. This indole
      inhibits nitric oxide synthetase activity and it is a potent scavenger of nitric
      oxide, which also plays an important role in the spread of the VEE virus. In
      conclusion, the immunomodulatory, antioxidant, and neuroprotective effects of
      melatonin suggest that this indole must be considered as an additional
      therapeutic alternative to fight viral diseases.

PMID- 14962058
TI  - Suppression of melatonin biosynthesis in the chicken pineal gland by retinally
      perceived light - involvement of D1-dopamine receptors.
AB  - In this study the role of retinal dopamine (DA) receptors in the light-induced
      suppression of melatonin biosynthesis in the chicken pineal gland was examined.
      Exposure of dark-adapted chickens to low intensity light (4 lux) at night
      significantly decreased the activity of serotonin N-acetyltransferase (AA-NAT;
      the penultimate and key regulatory enzyme in melatonin production) and melatonin
      content in the pineal gland. This suppressive action of light was blocked by
      intraocular (i.oc.) administration of SCH 23390 (a selective antagonist of D1-DA
      receptors), but was not affected by sulpiride (a selective antagonist of D2-DA
      receptors). Injection of DA (i.oc.) to dark-adapted chickens significantly
      decreased pineal AA-NAT activity and melatonin content in a dose- and time
      dependent manner. The action of DA was mimicked by selective agonists of D1-DA
      receptors, SKF 38393 and SKF 81297, and non-hydrolyzable analogs of cyclic AMP
      (cAMP), dibutyryl-cAMP and 8-bromo-cAMP. However, i.oc. administration of
      quinpirole, a selective agonist of D2-DA receptors, did not modify pineal AA-NAT
      activity. In contrast, quinpirole potently decreased nocturnal AA-NAT activity in
      the retina. Systemic administration of SCH 23390 to chickens blocked the i.oc. DA
      evoked decline in nighttime pineal AA-NAT activity, whereas sulpiride was
      ineffective. These findings indicate that light activation of retinal
      dopaminergic neurotransmission, with concomitant stimulation of D1-DA receptors
      positively coupled to the cAMP generating system, plays an important role in a
      cascade of events regulating pineal activity.

PMID- 14962059
TI  - Acutely administered melatonin decreases somatostatin-binding sites and the
      inhibitory effect of somatostatin on adenylyl cyclase activity in the rat
      hippocampus.
AB  - Melatonin is known to increase neuronal activity in the hippocampus, an effect
      contrary to that of somatostatin (somatotropin release-inhibiting factor, SRIF).
      Thus, the aim of this study was to investigate whether the somatostatinergic
      system is implicated in the mechanism of action of melatonin in the rat
      hippocampus. One group of rats was injected a single dose of melatonin [25
      microg/kg subcutaneously (s.c.)] or saline containing ethanol (0.5%, s.c.) and
      killed 5 hr later. Melatonin significantly decreased the SRIF-like
      immunoreactivity levels and induced a significant decrease in the density of SRIF
      receptors as well as in the dissociation constant (Kd). SRIF-mediated inhibition
      of basal and forskolin-stimulated adenylyl cyclase activity was markedly
      decreased in hippocampal membranes from melatonin-treated rats. The functional
      activity of Gi proteins was similar in hippocampal membranes from melatonin
      treated and control rats. Western blot analyses revealed that melatonin
      administration did not alter Gialpha1 or Gialpha2 levels. To determine if the
      changes observed were related to melatonin-induced activation of central
      melatonin receptors, a melatonin receptor antagonist, luzindole, was administered
      prior to melatonin injection. Pretreatment with luzindole (10 mg/kg, s.c.) did
      not alter the melatonin-induced effects on the above-mentioned parameters and
      luzindole, alone, had no observable effect. The present results demonstrate that
      melatonin decreases the activity of the SRIF receptor-effector system in the rat
      hippocampus, an effect which is apparently not mediated by melatonin receptors.
      As SRIF exerts an opposite effect to that of melatonin on hippocampal neuronal
      activity, it is possible that the SRIFergic system could be implicated in the
      mechanism of action of melatonin in the rat.

PMID- 14962060
TI  - Indole-based analogs of melatonin: in vitro antioxidant and cytoprotective
      activities.
AB  - The known neuroprotective actions of melatonin could be due to its antioxidant or
      radical scavenging activity, or they could be due to specific interactions of the
      indole with its receptors. A study of structure-activity relationships may
      provide useful information when a validated macromolecular target has not been
      (or is not) identified. A set of indole derivatives, with changes in the 5
      methoxy and acylamino groups, the side chain position and the
      lipophilic/hydrophilic balance, were selected and tested for their in vitro
      antioxidant potency in the ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic
      acid disodium salt) and thiobarbituric acid reactive substances (TBARS) assays
      and for their cytoprotective activity against kainate excitotoxicity on
      cerebellar cell cultures. No quantitative model was able to relate the potencies
      obtained in the two antioxidant assays, probably because they are related to
      different physico-chemical properties. However, the lipophilicity of the
      compounds and the antioxidant potency in the TBARS assay were linearly
      correlated. This may be due to improved access to the lipidic substrate, where
      the antioxidant action occurs. In the cytoprotection assay, most compounds showed
      potencies comparable with or lower than melatonin. An exception was N-[2-(5
      methoxy-1H-indol-2-yl)ethyl]acetamide (12), yielding, at 50 microM, percentages
      of cell vitality higher than 75%, while melatonin EC50 was 333 microM. No
      correlation was observed between cytoprotective and antioxidant potencies, nor
      with MT1 or MT(2) receptor affinity. Compound 12 is a low-affinity antagonist at
      melatonin membrane receptors, and one of the most potent compounds in the
      antioxidant assays; its cytoprotective potency and the absence of agonist
      activity at melatonin membrane receptors make it a valid candidate for further
      investigations.

PMID- 14962061
TI  - Central nervous alpha1-adrenoceptor stimulation induces duodenal luminal release
      of melatonin.
AB  - Intracerebroventricular (i.c.v.) infusion of the alpha1-adrenoceptor agonist
      phenylephrine elicits vagal and sympathetic neural stimulation of the bicarbonate
      secretion by the duodenal mucosa. Melatonin originating from mucosal
      enterochromaffin cells (EC cells) has been proposed to mediate this centrally
      elicited stimulation. However, the release of intestinal melatonin has not been
      studied. Rats were anesthetized with thiobarbiturate, a 12-mm segment of duodenum
      with intact blood supply was cannulated in situ and bicarbonate secretion
      titrated by pH-stat. The mean arterial blood pressure was continuously recorded.
      Melatonin in the duodenal luminal perfusate was determined by high-performance
      liquid chromatography with electrochemical detection. Intracerebroventricular
      infusion of phenylephrine (12.2 microM/kg/hr) induced more than 10-fold increase
      in release of melatonin into the duodenal lumen and an increase in HCO secretion
      from 7.6 +/- 0.5 to 18.6 +/- 2.1 microEq/cm/hr. The melatonin receptor (MT2 >
      MT1) antagonist luzindole (600 nM/kg, i.v.) almost abolished the marked rise in
      bicarbonate secretion induced by i.c.v. phenylephrine but, in contrast, did not
      affect the release of melatonin. These results strongly suggest that release of
      melatonin from the mucosa mediates the duodenal secretory response to centrally
      elicited neural stimulation.

PMID- 14962062
TI  - Melatonin receptor agonist 2-iodomelatonin prevents apoptosis of cerebellar
      granule neurons via K(+) current inhibition.
AB  - Activation of K(+) current plays a critical role in the control of programmed
      cell death. In the present study, whole-cell patch-clamp recording, a caspase-3
      activity assay, and flow cytometric analysis were used to examine the effects of
      the MT2 melatonin receptor agonist 2-iodomelatonin on the delayed-rectifier K(+)
      current (IK) and the prevention of apoptosis. It was found that apoptosis of
      cerebellar granular neurons induced by low-K(+) (5 mm) incubation was associated
      with an increase in IK amplitude and caspase-3 activity. After 6 hr of low-K(+)
      treatment, IK was increased by 45% (n = 86). Flow cytometry showed that the
      apoptosis rate increased by 333% compared with the control neurons. In addition,
      exposure of cultured granule cells to low K(+) also resulted in a significant
      activation of caspase-3, by 466%. 2-Iodomelatonin (10 microm in injection
      pipette) inhibited the IK amplitude recorded from control cells and from cells
      undergoing apoptosis. However, 2-iodomelatonin only modified the IK-channel
      activation kinetics of cells under both conditions. Furthermore, 2-iodomelatonin
      reduced the rate of apoptosis and caspase-3 activation, by 66 and 64%,
      respectively. The melatonin receptor antagonist, 4P-PDOT, abrogated the effect of
      2-iodomelatonin on the IK augmentation, caspase-3 activity, and apoptosis. These
      results suggest that the neuroprotective effects of melatonin are not only
      because of its function as a powerful antioxidant, but also to its interactions
      with specific receptors. The effect of 2-iodomelatonin against apoptosis may be
      mediated by activating a melatonin receptor, which modulates IK channels and
      reduces K(+) efflux.

PMID- 14962063
TI  - Effect of melatonin on temporal changes of reactive oxygen species and
      glutathione after MPP(+) treatment in human astrocytoma U373MG cells.
AB  - 1-Methyl-4-phenylpyridinium (MPP(+)) ion, a toxic metabolite of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine, is produced by monoamine oxidase B in astrocytes.
      MPP(+) causes a selective dopaminergic neurodegeneration, the pathophysiologic
      hallmark of Parkinson disease. However, the toxic effect of MPP(+) on astrocytes
      remains unclear. Here, we examined the effect of MPP(+) on human astrocytoma
      U373MG cells, with particular attention to the temporal interaction of
      glutathione (GSH) and reactive oxygen species (ROS) (H2O2 and O). MPP(+) induced
      astrocyte apoptosis in a dose-dependent manner 48 hr after treatment. Distinctive
      early (<6 hr) and late (24-48 hr) responses were observed. ROS production and the
      oxidized GSH (GSSG)/GSH ratio, indicators of oxidative stress, rose dramatically
      after 24 hr of MPP(+) exposure, whereas the H2O2 level transiently decreased at 6
      hr. ROS overproduction and GSH dysfunction were concomitantly associated with
      caspase-3 activation and finally led to cell apoptosis. Moreover, GSH depletion
      by diethyl maleate, but not buthionine sulfoximine, caused cells to die quickly
      and potentiated the cytotoxicity of MPP(+). Co-treatment with melatonin, a known
      antioxidant secreted by the pineal gland, significantly prevented cell apoptosis
      by inhibiting oxidative stress and caspase-3 activation, but it did not affect
      that the early changes due to MPP(+) treatment. Our results demonstrate that in
      astrocytes, GSH is involved in the early decrease and late increase in ROS levels
      induced by MPP(+) treatment. Melatonin remedies the dysfunction of GSH system to
      block caspase-3 activation and cell apoptosis induced by oxidative stress during
      the long-term exposure of MPP(+).

PMID- 14962064
TI  - Attenuation of cold-induced apoptosis by exogenous melatonin in carrot suspension
      cells: the possible involvement of polyamines.
AB  - Pretreatment with 43 nM (10 ng/mL) to 86 nM melatonin for 5 days significantly
      attenuated cold-induced apoptosis in carrot suspension cells (Daucus carota L.)
      as evidenced by the TUNEL procedure, DNA fragmentation and the morphological
      changes revealed by electronic microscopy observations. The antiapoptotic effect
      of melatonin was initially thought to be a result of its antioxidant actions. In
      our study, however, reactive oxygen species (ROS) generation remained unaffected
      by melatonin treatment, suggesting that melatonin plays its protective role not
      related to its direct ROS scavenger. At the same time, notable increases in
      putrescine and spermidine levels were observed in melatonin-treated cells, which
      may be responsible for the alleviation of the cold-induced apoptosis. The
      possible involvement of polyamines in the antiapoptotic effect of melatonin was
      further confirmed by the inhibitory effect of exogenous polyamines on apoptosis
      as displayed by the DNA laddering assay.

PMID- 14962065
TI  - Pinealectomy induces malformation of the spine and reduces the mechanical
      strength of the vertebrae in Atlantic salmon, Salmo salar.
AB  - This study describes the long-term effects of surgical ablation of the pineal
      gland on the spine of 3-yr-old Atlantic salmon (Salmo salar L.) with a mean
      weight of 3.2 kg. Radiographic examinations showed that 82% of the
      pinealectomized fish developed marked lateral (scoliosis) and dorso-ventral
      spinal curvatures. The proportions of the individual vertebral bodies and their
      mechanical properties were also altered. The stiffness, yield limit and
      resilience of the vertebral bodies, as measured by compression in the cranio
      caudal direction, were significantly lower in the pinealectomized than in the
      sham-pinealectomized group. Calcium, phosphorous and total mineral content of the
      vertebral bodies were also significantly lower in the pinealectomized fish, while
      these parameters were similar in scales in the two groups. Alterations of the
      spinal curve accompanied by changes in the proportions, mechanical strength and
      mineral content of the vertebral bodies of the pinealectomized salmon indicate
      that melatonin has several functions related to vertebral bone growth. As the
      lesions found in salmon are similar to the spinal malformations observed in avian
      species and mammals after pinealectomy, this study strengthens the hypothesis of
      a phylogenetically conserved function of the pineal gland related to skeletal
      development.

PMID- 14962066
TI  - Differential effects of light wavelength in phase advancing the melatonin rhythm.
AB  - Shorter wavelength light has been shown to be more effective than longer
      wavelengths in suppressing nocturnal melatonin and phase delaying the melatonin
      rhythm. In the present study, different wavelengths of light were evaluated for
      their capacity to phase advance the saliva melatonin rhythm. Two long
      wavelengths, 595 nm (amber) and 660 nm (red) and three shorter wavelengths, 470
      nm (blue), 497 nm (blue/green), and 525 nm (green) were compared with a no-light
      control condition. Light was administered via a portable light source comprising
      two light-emitting diodes per eye, with the irradiance of each diode set at 65
      microW/cm(2). Forty-two volunteers participated in up to six conditions resulting
      in 15 per condition. For the active light conditions, a 2-hr light pulse was
      administered from 06:00 hr on two consecutive mornings. Half-hourly saliva
      samples were collected on the evening prior to the first light pulse and the
      evening following the second light pulse. The time of melatonin onset was
      calculated for each night and the difference was calculated as a measure of phase
      advance. The shorter wavelengths of 470, 495 and 525 nm showed the greatest
      melatonin onset advances ranging from approximately 40-65 min while the longer
      wavelengths produced no significant phase advance. These results strengthen
      earlier findings that the human circadian system is more sensitive to the short
      wavelengths of light than the longer wavelengths.

PMID- 14962068
TI  - Message from the new Editor-in-Chief of the Journal of Neuroendocrinology.

PMID- 14962067
TI  - Butterflies, grasshoppers and editors.

PMID- 14962069
TI  - Dual excitatory and inhibitory effects of stimulation of intrinsic innervation of
      the anterior pituitary on adrenocorticotropic hormone release in the rat.
AB  - The gland cells of the mammalian anterior pituitary are innervated by substantial
      amounts of nerve fibres, and there is evidence that the nerve fibres are
      functionally active. In the rat, the nerve fibres make typical excitatory
      synapses with corticotropes. The physiological significance of this synaptic
      relationship was investigated in the present study. The anterior pituitary of the
      rat was sliced and stimulated with electrical field in a chamber. The perfusate
      was continuously collected and immunoradioassayed for adrenocorticotropic hormone
      (ACTH). When the gland slices were stimulated at a high frequency of 10 Hz, there
      was a significant inhibition of ACTH secretion. Stimulation at a low frequency of
      2 Hz resulted in a quick and transient excitation of ACTH release. The results
      indicate that stimulation of the nerve fibres in the anterior pituitary has dual
      excitatory and inhibitory effects on ACTH secretion.

PMID- 14962070
TI  - Regulation of galanin-like peptide gene expression by pituitary hormones and
      their downstream targets.
AB  - Galanin-like peptide (GALP) mRNA is expressed in neurones of the hypothalamic
      arcuate nucleus and within pituicytes in the neurohypophysis. Several
      neuropeptides that are expressed in the arcuate nucleus participate in the
      neuroendocrine regulation of pituitary hormone secretion. Our objective was to
      determine the extent to which GALP might be a target for regulation by pituitary
      hormones or their downstream targets in the rat. The expression of GALP mRNA in
      the arcuate nucleus was reduced by hypophysectomy as determined by in situ
      hybridization. However, this did not appear to be attributable to the loss of
      either gonadal or adrenal steroids because castrated, ovariectomized and
      adrenalectomized rats had GALP mRNA expression that was indistinguishable from
      their respective controls. Next, we investigated the effects of growth hormone
      deficiency on GALP mRNA expression by studying dwarf rats and found that GALP
      gene expression was not different between dwarf rats and controls. We found that
      thyroidectomy led to a significant reduction in GALP mRNA expression compared to
      intact controls, and thyroidectomized rats implanted with thyroxine pellets had
      GALP mRNA expression that was similar to intact controls. Thus, the reduction of
      GALP mRNA expression seen in hypophysectomized animals may reflect, in part, a
      selective loss of thyroid hormone. We also found that the expression of GALP mRNA
      was increased in the neurohypophysis of lactating rats compared to nonlactating
      rats, whereas GALP mRNA expression in the arcuate nucleus was unaffected by
      lactation. This suggests that the induction of GALP gene expression in pituicytes
      is physiologically associated with activation of oxytocin and vasopressin
      secretion during lactation.

PMID- 14962071
TI  - Activity-dependent dynamics of coexisting brain-derived neurotrophic factor, pro
      opiomelanocortin and alpha-melanophore-stimulating hormone in melanotrope cells
      of Xenopus laevis.
AB  - Brain-derived neurotrophic factor (BDNF) is involved as an autocrine factor in
      the regulation of the secretory activity of the neuroendocrine pituitary
      melanotrope cells of Xenopus laevis. We studied the subcellular distribution of
      BDNF in Xenopus melanotropes using a combination of high-pressure freezing,
      cryosubstitution and immunoelectron microscopy. Presence of BDNF, pro
      opiomelanocortin (POMC) and alpha-melanophore-stimulating hormone (alphaMSH)
      within melanotrope secretory granules was studied by triple-labelling
      immunoelectron microscopy. In addition, intracellular processing of BDNF was
      investigated by quantifying the number of immunogold particles in different
      stages of secretory granule maturation, in animals adapted to black or white
      background light conditions. The high-pressure freezing technique provides
      excellent preservation of both cellular ultrastructure and antigenicity. BDNF
      coexists with POMC and alphaMSH within secretory granules. BDNF-immunoreactivity
      increases along the secretory granule maturation axis (i.e. from electron-dense,
      via moderately electron-dense, to electron-lucent secretory granules). Immature,
      low immunoreactive, electron-dense secretory granules are assumed to contain
      mainly or even exclusively proBDNF. Strongly immunoreactive electron-lucent
      secretory granules represent the mature granule stage in which proBDNF has been
      processed to mature BDNF. Furthermore, in moderately electron-dense secretory
      granules, immunoreactivity is markedly (+79%) higher in black-adapted than in
      white-adapted animals, indicating that stimulation of melanotrope cell activity
      by the black background condition speeds up processing of BDNF from its precursor
      in this granule stage. It is concluded that, in the Xenopus melanotrope, BDNF
      biosynthesis and processing occur along the secretory granule maturation axis,
      together with that of POMC-derived alphaMSH, and that the environmental light
      condition not only controls the biosynthesis and secretion of BDNF and of POMC
      end-products, but also regulates the rate of their intragranular processing.

PMID- 14962072
TI  - Identification of neurones in the female rat hypothalamus that express oestrogen
      receptor-alpha and vesicular glutamate transporter-2.
AB  - Oestrogen exerts its effects in the brain by binding to and activating two
      members of the nuclear receptor family, oestrogen receptor (ER)-alpha and ER
      beta. Evidence suggests that oestrogen-receptive neurones participate in the
      generation of reproductive behaviours and that they convey the oestrogen message
      to gonadotropin-releasing hormone (GnRH) neurones. The aim of the present study
      was to identify the neurochemical phenotype of a subset of oestrogen receptor
      expressing neurones. To this aim, we focused on the glutamate neuronal system,
      which is one of the most important stimulators of GnRH synthesis and release. We
      used the presence of vesicular glutamate transporter-2 (VGLUT2) mRNA as a
      specific marker to identify glutamate neurones and employed dual in situ
      hybridization to localize ERalpha mRNA-(35S-labelling) and VGLUT2 mRNA
      (digoxigenin-labelling) expressing neurones within the hypothalamus. The results
      show that the overall distribution of VGLUT2 mRNA and ERalpha mRNA are consistent
      with previous data in the literature. Dual-labelled neurones were localized in
      the ventrolateral part of the ventromedial nucleus where 81.3 +/- 3.4% of the
      ERalpha mRNA containing neurones expressed VGLUT2 mRNA, in the anteroventral
      periventricular nucleus (30% colocalization) and in the medial preoptic nucleus
      (19% colocalization). Only 4.4% of the ERalpha expressing neurones in the arcuate
      nucleus contained VGLUT2 mRNA. These findings reveal that certain subpopulations
      of oestrogen-receptive neurones are glutamatergic in select hypothalamic areas
      that are known to regulate reproductive behaviour and GnRH neurones in the female
      rat. Thus, the oestrogen signal could be propagated through glutamate neurones to
      distant sites and influence the activity of the postsynaptic neurones.

PMID- 14962073
TI  - Effect of streptozotocin-induced diabetes on rat brain mitochondria.
AB  - This study evaluated several parameters related to mitochondrial function and
      oxidative stress in streptozotocin (STZ)-treated rats, a model of type 1
      diabetes. For this purpose, the respiratory indexes (RCR and ADP/O ratio),
      mitochondrial transmembrane potential (DeltaPsim), repolarization lag phase,
      repolarization level, mitochondrial enzymatic activities, ATP and malondialdehyde
      (MDA) levels, reduced glutathione (GSH), vitamin E and cardiolipin contents were
      determined in rat brain mitochondria isolated after 4 and 9 weeks after STZ
      treatment. Brain mitochondria isolated from citrate (vehicle)-treated Wistar rats
      were used as control. We observed that STZ-induced diabetes did not substantially
      affect brain mitochondrial function. Instead, 4-week diabetic rats presented
      higher mitochondrial respiratory chain enzymatic activities, especially succinate
      cytochrome C reductase activity, compared to 4-week control rats. In 9-week
      diabetic rats, only a significant decrease in cardiolipin content was observed;
      however, a significant increase in mitochondrial GSH content occurred. All other
      parameters analysed remained statistically unchanged. From these results, we
      conclude that STZ-induced diabetes did not promote brain mitochondrial
      dysfunction, suggesting that oxidative stress associated with type 1 diabetes is
      not directly related to mitochondrial dysfunction, but probably is related to
      extramitochondrial factor(s).

PMID- 14962074
TI  - Expression of the arginine vasopressin gene in response to salt loading in
      oxytocin gene knockout mice.
AB  - Accumulating evidence suggests that both oxytocin and arginine vasopressin (AVP)
      are vital components in the regulation of body fluid balance. However, the
      physiological role of oxytocin and possible cooperative interactions between
      oxytocin and AVP in sodium balance remain obscure, even though recent studies
      using oxytocin knockout (OTKO) mice suggested that oxytocin may contribute to the
      regulation of salt appetite. In the present study, we examined the effects of
      salt loading (drinking 2% NaCl for 5 days) on the expression of the AVP gene in
      the paraventricular (PVN) and supraoptic nuclei (SON) of wild-type, OTKO and
      heterozygous littermates using in situ hybridization histochemistry. In addition,
      the effects of salt loading on the expression of the oxytocin gene were also
      examined in wild-type and heterozygous mice. Under the non salt-loaded condition,
      the levels of AVP mRNA in the PVN and SON of OTKO mice were significantly
      decreased compared to those in wild-type mice. Nevertheless, the up-regulation of
      the expression of the AVP gene in response to salt loading was preserved in OTKO
      mice. The degree of the up-regulation in OTKO mice tended to be greater compared
      to those in wild-type mice, suggesting compensatory up-regulation of the
      expression of the AVP gene in OTKO mice after salt loading. The basal levels of
      oxytocin mRNA in the PVN and SON of heterozygous mice were significantly lower
      than those in wild-type mice. Salt loading caused an increase of oxytocin mRNA
      levels in the PVN and SON of both wild-type and heterozygous mice. The ratios of
      increase of oxytocin mRNA levels were very similar between wild-type and
      heterozygous mice, suggesting that the single remaining oxytocin gene in
      heterozygous mice responds normally to an osmotic cue. Finally, salt loading
      tended to increase the serum concentration of sodium regardless of genotype, and
      there were no genotype differences in both the control and salt-loaded groups.
      These results suggest ways in which oxytocin may play a cooperative role together
      with AVP in the regulation of sodium balance.

PMID- 14962075
TI  - Circadian rhythm of melatonin release from the photoreceptive pineal organ of a
      teleost, ayu (Plecoglossus altivelis) in flow-thorough culture.
AB  - In the present study, we tested whether the pineal organ of ayu (Plecoglossus
      altivelis), an osmerid teleost close relative of salmonids, harbours a circadian
      oscillator regulating rhythmic melatonin release using flow-through culture. The
      pineal organ maintained under light/dark cycles released melatonin in a rhythmic
      fashion with high levels during the dark phase. A circadian rhythm of melatonin
      release persisted in constant darkness for at least four cycles. Characteristics
      of the circadian rhythm (free-running period, phase and amplitude) exhibited
      small variations among cultures when the data was normalized, indicating that
      this system is sufficient for the analysis of the circadian rhythm both at
      qualitative and quantitative levels. Six-hour extension of the light phase from
      the normal onset time of the dark phase or exposure to constant light for 36 or
      48 h before transfer to constant darkness significantly inhibited melatonin
      release. Phase shifts in the circadian rhythm of melatonin release were also
      observed. Thus, the ayu pineal organ contains all the three essential components
      of the circadian system (a circadian clock, the photoreceptor responsible for
      photic entrainment of the clock, and melatonin generating system as an output
      pathway). This system should provide a useful model for analysing the
      physiological and molecular basis of the vertebrate circadian system. In
      addition, further comparative studies using salmonids and related species
      including ayu will provide some insight into the evolution of the roles of the
      pineal organ in the vertebrate circadian system.

PMID- 14962076
TI  - The dynamics of the hypothalamic-pituitary-adrenal axis during maternal
      deprivation.
AB  - A close contact between the dam and the litter is essential for the normal
      development of the hypothalamic-pituitary-adrenal (HPA) axis in rats and mice.
      Maternal signals, as licking and feeding, have been shown to sustain the HPA axis
      of the pups in a hypo-responsive state. Disruption of this mother-pup interaction
      by 24 h of maternal deprivation activates the otherwise quiescent stress system
      of the neonates, resulting in an enhanced adrenal sensitivity to
      adrenocorticotropic hormone (ACTH) and a decreased expression of central HPA
      markers, such as corticotropin-releasing hormone (CRH). However, the dynamics of
      these central and peripheral changes over the 24h period are largely unknown. In
      this study, we examined the time course of some of the central and peripheral
      indices of HPA activity during 24 h of maternal deprivation. We measured
      corticosterone and ACTH in the blood as well as CRH, mineralocorticoid and
      glucocorticoid receptor expression in the brain. Our results demonstrate that
      each of the components of the HPA axis responds to maternal deprivation at
      different time points following removal of the mother and with a very specific
      time course. The main activation of the HPA axis occurred between 4 h and 8 h of
      maternal absence. By contrast, during the second half of the deprivation period,
      negativefeedback mechanisms restrained the further increase in ACTH and
      corticosterone release. We conclude that maternal deprivation triggers a cascade
      of sequential changes at the various levels of the stress system, and that
      measuring only one aspect of the system at one time point does not accurately
      reflect the dynamic alterations of the HPA axis.

PMID- 14962077
TI  - Reduced progesterone metabolites protect rat hippocampal neurones from kainic
      acid excitotoxicity in vivo.
AB  - The ovarian hormone progesterone is neuroprotective in some animal models of
      neurodegeneration. Progesterone actions in the brain may partly be mediated by
      the locally produced metabolites 5alpha-dihydroprogesterone and 3alpha,5alpha
      tetrahydroprogesterone. The neuroprotective effects of these two metabolites of
      progesterone were assessed in this study. Ovariectomized Wistar rats were
      injected with kainic acid, to induce excitotoxic neuronal death in the
      hippocampus, and with different doses of 5alpha-dihydroprogesterone and
      3alpha,5alpha-tetrahydroprogesterone. The number of surviving neurones in the
      hilus of the dentate gyrus of the hippocampus was assessed with the optical
      disector method. The administration of kainic acid resulted in a significant
      decrease in the number of hilar neurones and in the induction of vimentin
      expression in reactive astrocytes, a sign of neural damage. Low doses of 5alpha
      dihydroprogesterone (0.25 and 0.5 mg/kg body weight, b.w.) prevented the loss of
      hilar neurones and the appearance of vimentin immunoreactivity in astrocytes.
      Higher doses (1-2 mg/kg b.w.) were not neuroprotective. By contrast, low doses of
      3alpha,5alpha-tetrahydroprogesterone (0.25-1 mg/kg b.w.) were unable to protect
      the hilus from kainic acid while higher doses (2-4 mg/kg b.w.) were protective.
      The different optimal neuroprotective doses of 5alpha-dihydroprogesterone and
      3alpha,5alpha-tetrahydroprogesterone suggest that these two steroids may protect
      neurones using different mechanisms. The neuroprotective effects of 3alpha,5alpha
      tetrahydroprogesterone may be exerted by the inhibition of neuronal activity via
      the GABAA receptor. This latter possibility is supported by the observation that
      3beta,5alpha-tetrahydroprogesterone, an isomer of 3alpha,5alpha
      tetrahydroprogesterone that does not bind to GABAA receptor, was not
      neuroprotective. In summary, our findings suggest that progesterone
      neuroprotective effects may be, at least in part, mediated by its reduced
      metabolites 5alpha-dihydroprogesterone and 3alpha,5alpha-tetrahydroprogesterone.

PMID- 14962078
TI  - Gender differences in the expression of galanin and vasoactive intestinal peptide
      in oestrogen-induced prolactinomas of Fischer 344 rats.
AB  - We have previously described a sexual dimorphism in oestrogen-induced anterior
      pituitary tumorigenesis in Fischer 344 rats, with female tumours averaging twice
      the size of those of males. Neonatal androgenization of female Fischer 344 rats
      with 100 micro g of testosterone propionate reverted that effect, causing a 'male
      like' phenotype. The peptides galanin and vasoactive intestinal peptide (VIP) are
      possible mediators of oestrogen effects on the anterior pituitary, including
      hyperprolactinemia and lactotroph proliferation. To further extend our previous
      findings, we investigated the expression of galanin and VIP in the anterior
      pituitary of control and oestrogenized male, female and neonatally androgenized
      female Fischer 344 rats. At 3 months of age, rats were deprived of their gonads
      and divided into control and diethylstilbestrol (DES)-treated groups. In the
      anterior pituitary of control rats, galanin and VIP immunoreactive cells were
      absent. However, in DES-treated rats, pituitaries from normal ovariectomized
      females showed higher number of galanin and VIP positive cells than pituitaries
      from neonatally androgenized ovariectomized females and gonadectomized males.
      This pattern correlated with changes in anterior pituitary weight and serum
      prolactin. Our study suggests that sexual differences in oestrogen-induced
      pituitary tumorigenesis could be due to the differential expression of galanin
      and VIP. Furthermore, our data support the fact that neonatal exposure to
      androgens, as in normal males and androgenized females, may condition the
      response of the pituitary gland to oestrogens in adult life.

PMID- 14962079
TI  - Alpha1 adrenoreceptors mediate the stimulatory effects of oestrogen on stress
      related hypothalamic-pituitary-adrenal activity in the female rat.
AB  - Variation in challenge-induced adrenocorticotropin hormone (ACTH) release over
      the oestrous cycle occurs in response to fluctuations in circulating
      concentrations of oestrogen and progesterone. However, how these ovarian steroids
      interact to regulate the principal ACTH cosecretagogues, corticotropin-releasing
      hormone (CRH) and arginine vasopressin is not understood. Here, we measured
      median eminence CRH and vasopressin content in intact cycling female rats, and in
      ovariectomized (OVX) females steroid-replaced in a manner that approximates the
      relative release patterns of oestrogen and progesterone seen over the oestrous
      cycle. Intact cycling females showed significantly higher median eminence CRH and
      vasopressin concentrations during proestrous and oestrous compared to the
      diestrous phase. In OVX rats, a single 10 micro g injection of oestrogen failed
      to mimic this increase in median eminence CRH and vasopressin. However, this dose
      significantly elevated CRH and vasopressin content in OVX rats previously exposed
      to diestrous concentrations of oestrogen and progesterone. Moreover, oestrogen
      priming enhanced restraint-induced depletion of CRH and vasopressin from the
      median eminence, but only against a background of low oestrogen and progesterone
      replacement. Oestrogen-induced elevations in median eminence vasopressin (but not
      CRH) content were reduced by peripheral administration of the alpha1
      adrenoreceptor antagonist prazosin. Finally, plasma ACTH concentrations following
      central injection of the alpha1 receptor agonist, phenylephrine, were
      significantly higher in rats during proestrous compared to diestrous. These
      results indicate that the stimulatory effect of oestrogen on both the expression
      and stress-induced release of ACTH cosecretagogues is exerted only against a
      background of low oestrogen and progesterone levels, and is mediated, in part,
      via the alpha1 adrenoreceptor.

PMID- 14962080
TI  - Central and peripheral immunoreactivity of melanin-concentrating hormone in
      hypothalamic obese and lactating rats.
AB  - Melanin-concentrating hormone (MCH) is believed to be an important orexigenic
      peptide mainly localized in the lateral hypothalamic area. Its involvement in the
      hyperphagia induced by hypothalamic lesions and lactation remains unclear. In
      this study, we investigated MCH immunoreactivity in the hypothalamus using
      immunohistochemistry and MCH concentration in the peripheral circulation using an
      enzyme immunoassay in rats with a lesion in the ventromedial hypothalamus or the
      paraventricular nucleus, and in lactating rats. Bilateral lesions of the
      ventromedial or paraventricular nuclei were performed using an electrolytic
      method. Quantification of immunoreactivity by image analysis revealed that the
      number and mean staining intensity of MCH-immunoreactive neurones in the lateral
      hypothalamic area and the zona incerta were significantly decreased by both types
      of lesions compared to sham controls, whereas circulating MCH concentration was
      not significantly different on day 7 postlesion. By contrast, in lactating rats
      on days 11-12 postpartum, the expression of MCH in the lateral hypothalamic area
      and the zona incerta was significantly increased compared to nonlactating
      controls. Circulating MCH concentration was not changed in lactating rats. These
      results suggest that hyperphagia induced by lactation, but not hypothalamic
      lesion, might be induced by excessive expression of MCH in the lateral
      hypothalamic area and the zona incerta.

PMID- 14962081
TI  - Altered expression of p53 mRNA in the brain and pituitary during repeated
      immobilization stress: negative correlation with glucocorticoid receptor mRNA
      levels.
AB  - In our previous study, apparent reduction of glucocorticoid receptor (GR) mRNA
      was seen in the hippocampus and the hypothalamic paraventricular nucleus (PVN)
      during repeated immobilization (IMO) stress, but not following starvation. Our
      laboratory has also shown that the sp1 activates, whereas tumour suppressor p53
      represses the promoter activity of GR gene. In an attempt to reveal the
      possibility that transcription factors such as sp1 and/or p53 are involved in the
      regulation of GR mRNA expression in the hippocampus and in the PVN in vivo, we
      examined the expression of GR mRNA, p53 mRNA, and sp1 mRNA in the hippocampus and
      in the PVN during repeated IMO and following starvation. In addition, the
      expression of these mRNAs was examined in the anterior pituitary, another GR-rich
      area. GR mRNA in all subfields of the hippocampus was robustly decreased, while
      GR mRNA in the anterior pituitary was increased, 24 h following 4 x IMO (2 h
      daily, for 4 consecutive days) and immediately after 5 x IMO. GR mRNA in the PVN
      was significantly decreased immediately after 5 x IMO, but not at 24 h after 4 x
      IMO. Conversely, p53 mRNA in the PVN and hippocampus was increased, whereas p53
      mRNA in the anterior pituitary was decreased, 24 h following 4 x IMO and
      immediately after 5 x IMO. Sp1 mRNA was unchanged in all areas examined following
      repeated IMO. Following 4 days of starvation, neither GR mRNA, p53 mRNA nor sp1
      mRNA showed any changes in the PVN and the hippocampus, except there was a minor
      decrease in GR mRNA in CA1-2. In the anterior pituitary, 4 days of starvation
      induced a minor, but significant increase in GR mRNA, whereas it decreased p53
      mRNA. Overall, regression analyses revealed a negative correlation between GR
      mRNA levels and p53 mRNA levels in CA1-2 and dentate gyrus of the hippocampus and
      in the anterior pituitary. GR mRNA in the PVN also showed a tendency towards the
      negative correlation with p53 mRNA levels. The results raise the possibility that
      p53 negatively regulates GR mRNA expression in the PVN, the hippocampus and the
      anterior pituitary during repeated immobilization stress.

PMID- 14962082
TI  - Insights into the molecular mechanism of chronic fibrosis: the role of connective
      tissue growth factor in scleroderma.
AB  - Connective tissue growth factor (CCN2), a member of the CCN family of proteins,
      is a cysteine-rich matricellular protein. Connective tissue growth factor is not
      normally expressed in dermal fibroblasts unless induced. The most potent inducer
      of connective tissue growth factor thus far identified is transforming growth
      factor beta. Connective tissue growth factor, however, is constitutively
      overexpressed by fibroblasts present in skin fibrotic lesions, including
      scleroderma. The overexpression of connective tissue growth factor present in
      fibrotic lesions contributes to the phenotype of scleroderma in that connective
      tissue growth factor promotes matrix deposition, and fibroblast adhesion and
      proliferation. In animal models, whereas either transforming growth factor beta
      or connective tissue growth factor alone produce only a transient fibrotic
      response, connective tissue growth factor and transforming growth factor beta act
      together to promote sustained fibrosis. Thus the constitutive overexpression of
      connective tissue growth factor by fibroblasts present in fibrotic lesions would
      be expected to contribute directly to chronic, persistent fibrosis. This review
      discusses recent information regarding insights into connective tissue growth
      factor biology and, using scleroderma as a model system, the part connective
      tissue growth factor might play in fibrotic disease.

PMID- 14962083
TI  - Topical estrogen accelerates hair regrowth in mice after chemotherapy-induced
      alopecia by favoring the dystrophic catagen response pathway to damage.
AB  - Estrogen receptor ligands are important modulators of skin physiology and are
      involved in the control of normal hair follicle cycling. Here, we have studied
      the effects of topically applied 17-beta-estradiol on pathologic hair follicle
      cycling as seen during chemotherapy-induced alopecia, one of the major unresolved
      problems of clinical oncology. For this study we employed a well-established
      murine model that mimics chemotherapy-induced alopecia in humans. For precisely
      quantifying the area of hair loss and hair regrowth in this model in vivo, we
      developed a simple planimetric assay (dotmatrix planimetry). We show that topical
      17-beta-estradiol significantly alters the cycling response of murine follicles
      to cyclophosphamide, whereas the estrogen antagonist ICI 182.780 exerted no such
      effects. Initially, topical 17-beta-estradiol enhanced chemotherapy-induced
      alopecia significantly by forcing the follicles into the dystrophic catagen
      response pathway to hair follicle damage, whereas follicles treated by ICI
      182.780 or vehicle shifted into the dystrophic anagen response pathway.
      Consequently, the regrowth of normally pigmented hair shafts after chemotherapy
      induced alopecia was significantly accelerated in the 17-beta-estradiol treated
      group. Our data encourage one to explore topical estrogens as a potential
      stimulant for hair re-growth after chemotherapy-induced alopecia.

PMID- 14962084
TI  - Variations of hair follicle size and distribution in different body sites.
AB  - For the evaluation and quantification of follicular penetration processes, the
      knowledge of variations of hair follicle parameters in different body sites is
      basic. Characteristics of follicle sizes and potential follicular reservoir were
      determined in cyanoacrylate skin surface biopsies, taken from seven different
      skin areas (lateral forehead, back, thorax, upper arm, forearm, thigh, and calf
      region). The highest hair follicle density and percentage of follicular orifices
      on the skin surface and infundibular surface were found on the forehead, whereas
      the highest average size of the follicular orifices was measured in the calf
      region. The highest infundibular volume and therefore a potential follicular
      reservoir was calculated for the forehead and for the calf region, although the
      calf region showed the lowest hair follicle density. The calculated follicular
      volume of these two skin areas was as high as the estimated reservoir of the
      stratum corneum. The lowest values for every other parameter were found on the
      forearm. The present investigation clearly contradicts former hypothesis that the
      amount of appendages of the total skin surface represents not more than 0.1%.
      Every body region disposes its own hair follicle characteristics, which, in the
      future, should lead us to a differential evaluation of skin penetration processes
      and a completely different understanding of penetration of topically applied
      drugs and cosmetics.

PMID- 14962085
TI  - Reciprocal regulation of thymus and activation-regulated chemokine/macrophage
      derived chemokine production by interleukin (IL)-4/IL-13 and interferon-gamma in
      HaCaT keratinocytes is mediated by alternations in E-cadherin distribution.
AB  - Keratinocytes produce many cytochemokines that are involved in the pathogenesis
      of skin disorders. In particular, the CC chemokines thymus and activation
      regulated chemokine (TARC)/macrophage-derived chemokine (MDC) play an important
      role in the infiltration of Th2 cells. This study was undertaken to examine the
      regulatory effects of interleukin (IL)-4, IL-13, and interferon (IFN)-gamma on
      TARC/MDC production in the human keratinocyte cell line HaCaT. HaCaT cells
      spontaneously secrete TARC and MDC. The production of TARC/MDC was downregulated
      by IL-4/IL-13, whereas it was upregulated by IFN-gamma. To explore these
      regulatory mechanisms, we investigated the capacity of cytokines to regulate
      expression of several adhesion molecules that may affect TARC/MDC production. Of
      the adhesion molecules examined, the constitutive surface expression of E
      cadherin was downregulated by IL-4/IL-13, but was upregulated by IFN-gamma.
      Moreover, disruption of the homophilic adherence of E-cadherin by anti-E-cadherin
      antibody or calcium chelation abolished the production of TARC/MDC. We further
      examined the distribution of the adherens junction complex composed of E
      cadherin, alpha-catenin, beta-catenin, and gamma-catenin. IL-4/IL-13 decreased
      the levels of membrane staining for adherens junction proteins, whereas IFN-gamma
      increased membrane staining. Taken together, these results suggest that IL-4/IL
      13 and IFN-gamma induce alternations in the distribution of adherens junctions in
      a different fashion and thereby contribute to the reciprocal regulation of
      TARC/MDC production.

PMID- 14962086
TI  - Microtubule-dependent redistribution of a cytoplasmic cornified envelope
      precursor.
AB  - Several cytoplasmic cornified envelope precursors have been described.
      Nevertheless, the mechanism whereby these proteins are positioned at the site of
      crosslink formation is not known. In this study, we examine the intracellular
      distribution of the cornified envelope precursor S100A11 (S100C) and the effects
      of the physiologic differentiating agent calcium on this distribution. S100A11 is
      localized in the cytoplasm of resting cultured human keratinocytes. Treatment
      with calcium causes S100A11 to relocate to the cell periphery.
      Immunoprecipitation studies reveal that S100A11 associates with microtubules, and
      inhibitor studies indicate that functional micro-tubules are required for S100A11
      peripheral redistribution. Parallel studies indicate that S100A11 is not present
      in the Golgi or endoplasmic reticulum (ER), suggesting that S100A11 is not moved
      to the cell periphery via the classical Golgi/ER export pathway. Further evidence
      that the Golgi/ER is not involved is provided by the observation that the
      Golgi/ER disruptor brefeldin A does not alter movement. These results suggest
      that redistribution along microtubules is a mechanism whereby S100A11 is
      positioned at the cell periphery in preparation for transglutaminase-dependent
      crosslinking. Staining of epidermal tissue sections from uninvolved and psoriatic
      epidermis reveals strong staining at the cell periphery in the majority of
      suprabasal cells, confirming a peripheral distribution of S100A11 in vivo.

PMID- 14962087
TI  - Mail surveys can achieve high response rates in a dermatology patient population.
AB  - In order to understand the burden of skin disease on patient populations,
      researchers need to be able to measure exposures and outcomes of interest in a
      population-based study. One method of obtaining such information is mailed
      patient surveys. This method of obtaining information, however, raises concerns
      regarding possible low response rates, and to the best of our knowledge, this
      method has not been attempted in large dermatology patient populations with a
      high response rate. We sought to determine whether using a slightly modified
      version of the Dillman Total Design Method as a mailed survey protocol would
      result in a high response rate in a dermatology population. A mail survey was
      sent using a slightly modified version of Dillman's Total Design Method to 4894
      patients seen in the Dermatology Department of the University of Pennsylvania,
      who were diagnosed with nonmelanoma skin cancer, dermatophytosis, acne rosacea,
      seborrheic keratosis, or warts; 74.1% of the subjects responded to the mailings;
      69.8% (n=3203) of patients returned a completed survey. Response rates (both as
      overall response and as survey completers only) were high across a wide spectrum
      of dermatologic illnesses and did not vary significantly by entry diagnosis.
      Dillman's Total Design Method appears to be an effective tool for researchers
      studying the burden of skin disease in a large sample of dermatology patients.

PMID- 14962088
TI  - Possible role of apoptosis in the pathogenesis of bleomycin-induced scleroderma.
AB  - To elucidate the role of apoptosis in cutaneous sclerosis, we examined the
      induction of apoptosis and expression of Fas, Fas ligand, as well as caspase-3 in
      a murine model of bleomycin-induced scleroderma. Dermal sclerosis was induced by
      local injections of bleomycin (1 mg per mL) in C3H/HeJ mice. Induction of
      apoptosis was examined by TUNEL (terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick end-labeling) assay and DNA gel electrophoresis.
      TUNEL positivity was prominently detected on keratinocytes and infiltrating
      mononuclear cells, but not endothelial cells and fibroblasts, in the lesional
      skin. DNA fragmentation revealed laddering at 3 to 4 wk following bleomycin
      treatment. Immunohistochemistry showed increased expression of Fas in
      infiltrating mononuclear cells at early phases following bleomycin exposure,
      whereas constitutive expression in fibroblasts. Fas ligand expression was
      increased in mononuclear cells as well as fibroblasts in the sclerotic skin.
      Results of reverse transcription-polymerase chain reaction analysis revealed that
      expression of Fas ligand mRNA was upregulated and reached a maximum at 3 wk,
      whereas Fas mRNA was continuously detected. mRNA expression as well as activity
      of caspase-3 was also enhanced at 3 wk. Administration of neutralizing anti-Fas
      ligand antibody together with local bleomycin treatment reduced the development
      of dermal sclerosis, associated with the reduction of TUNEL-positive mononuclear
      cells and also with the blockade of apoptosis. Caspase-3 activity in the lesional
      skin was also significantly reduced after anti-Fas ligand treatment. These
      findings suggest that excessive apoptosis, which is mediated by Fas/Fas ligand
      pathway and caspase-3 activation, is involved in the pathogenesis of bleomycin
      induced scleroderma, possibly by playing an inflammatory role.

PMID- 14962089
TI  - In psoriasis lesional skin the type I interferon signaling pathway is activated,
      whereas interferon-alpha sensitivity is unaltered.
AB  - The epidermal phenotype as observed in psoriatic skin results from inflammation
      and abnormal proliferation and terminal differentiation of keratinocytes. Mice
      deficient for interferon regulatory factor-2, a repressor of interferon
      signaling, display psoriasis-like skin inflammation. The development of this
      phenotype is strictly dependent on type I interferon (interferon-alpha/beta)
      signaling. The aim of this study was to assess the involvement of interferon
      alpha/beta in the pathogenesis of human psoriasis. In psoriatic skin, we measured
      an increased expression of components that play central and crucial roles in
      interferon-alpha/beta signal transduction. Culturing keratinocytes or healthy
      skin biopsies with recombinant interferon-alpha stimulated this signaling
      pathway; however, this did not induce the expression of markers that are
      generally used to define the psoriasis phenotype. Furthermore, skin from
      psoriasis patients responded identically to interferon-alpha stimulation,
      demonstrating that psoriatic skin does not have an aberrant sensitivity to type I
      interferon. We conclude that in psoriatic lesional skin the type I interferon
      signaling pathway is activated, despite an unaltered interferon-alpha
      sensitivity. Our data furthermore show that type I interferon, in contrast to
      interferon-gamma, does not act directly on keratinocytes to induce a psoriatic
      phenotype. Thus, if the observed activated type I interferon signaling is indeed
      functionally involved in the pathogenesis of psoriasis, its contribution might be
      indirect, putatively involving other cell types besides keratinocytes.

PMID- 14962090
TI  - Evaluation of the IRF-2 gene as a candidate for PSORS3.
AB  - Type 1 interferon can trigger flares of psoriasis. Hypersensitivity to type 1
      interferon signaling causes a psoriasis-like skin disease in mice deficient for
      the transcription factor interferon regulatory factor 2 (IRF2). The human IRF2
      gene is located at a previously identified candidate psoriasis susceptibility
      locus on chromosome 4q (PSORS3 at D4S1535). Therefore, we tested association of
      psoriasis with IRF2. We generated a sample consisting of 157 families with a
      total of 521 individuals. Five novel microsatellite markers were developed and
      typed, and complemented with three known markers to yield a set of eight markers
      spaced within 600 kb around the IRF2 gene, three of which are located in the
      gene. We detected association of IRF2 with type 1 psoriasis at two markers in the
      IRF2 gene. Haplotype sharing analysis confirmed association of IRF2 with type 1
      psoriasis (p=0.0017; pcorr=0.03). The 921G/A SNP in exon 9 was found to
      obliterate a predicted exon splice enhancer in an allele-specific manner. There
      was a suggestive increase of homozygosity for the splicing-deficient allele in
      type 1 psoriasis patients. Our data identify IRF2 as a potential susceptibility
      gene for psoriasis.

PMID- 14962091
TI  - Molecular consequences of deletion of the cytoplasmic domain of bullous
      pemphigoid 180 in a patient with predominant features of epidermolysis bullosa
      simplex.
AB  - Bullous pemphigoid antigen 2 (BP180; COL17A1) collagen gene mutations typically
      result in nonlethal junctional epidermolysis bullosa. We have identified a
      patient, who had phenotypic features of mainly epidermolysis bullosa simplex and
      evidence for both intraepidermal and junctional blister formation. Mutation
      analysis disclosed compound heterozygous mutations in the COL17A1 gene, leading
      to deletion of Ile-18 to Asn-407 from the intracellular domain of BP180, BP180
      Delta 18-407. To gain insight into the mechanisms underlying the phenotype, we
      have investigated the functional consequences of this truncation in BP180. The
      results demonstrate that: (1) in cultured keratinocytes of the patient, the
      assembly of hemidesmosomes, and their linkage with intermediate filaments are
      impaired; (2) BP180 Delta 18-407 is not capable of binding to the hemidesmosomal
      components BP230, plectin, and the beta 4 subunit of the alpha 6 beta 4 integrin
      in yeast two-hybrid assays; (3) BP180 Delta 18-407 is recruited into
      hemidesmosome-like structures in both normal and BP180-deficient transfected
      keratinocytes when ectopically expressed, suggesting that the extracellular
      domain of BP180 Delta 18-407 determines its topogenic fate; and, finally (4) the
      proteolytic shedding of the extracellular domain of BP180 Delta 18-407 is not
      impaired in transfected COS-7 cells. Collectively, the data demonstrate that the
      truncation of the intracellular domain of BP180 impairs the organization of
      hemidesmosomes, affecting both the mechanical stability of basal keratinocytes
      and dermoepidermal cohesion.

PMID- 14962092
TI  - Novel mechanism of revertant mosaicism in Dowling-Meara epidermolysis bullosa
      simplex.
AB  - The severe Dowling-Meara form of epidermolysis bullosa simplex is caused by
      dominant-negative mutations in keratins 5 and 14, which are specifically
      expressed in the basal keratinocytes of the epidermis. The most common mutation
      in the Dowling-Meara form of epidermolysis bullosa simplex patients is the
      missense mutation R125C in exon 1 of the K14 gene. We made a primary keratinocyte
      cell line from a sporadic case known to carry the R125C mutation as part of an
      ongoing gene therapy initiative. The full-length K14 cDNA was sequenced using
      keratinocyte mRNA. Unexpectedly, a second mutation was identified in K14: a
      heterozygous 1 bp insertion mutation (242insG) upstream of the R125C mutation.
      This frameshift mutation creates a premature termination codon immediately
      downstream, thereby nullifying the dominant-negative allele. The second mutation
      was only present in DNA derived from keratinocytes and was absent from lymphocyte
      DNA. This case represents a novel mechanism of revertant mosaicism and is an
      example of "natural gene therapy".

PMID- 14962093
TI  - Recurrent mutations in kindlin-1, a novel keratinocyte focal contact protein, in
      the autosomal recessive skin fragility and photosensitivity disorder, Kindler
      syndrome.
AB  - Kindler syndrome (OMIM 173650) is a rare autosomal recessive disorder
      characterized by trauma-induced blister formation (especially in childhood) and
      photosensitivity. Other features include mucocutaneous scarring and progressive
      poikiloderma. There is also an increased risk of skin and mucous membrane
      malignancy. The disorder was recently mapped to 20p12.3 and pathogenic mutations
      were identified in a new gene, KIND1. This gene encodes a 677 amino acid protein,
      kindlin-1, a component of focal contacts in keratinocytes. In this study, we
      identified four new recurrent mutations in KIND1 in 16 individuals with Kindler
      syndrome from 13 families of Pakistani (676insC), UK Caucasian (E304X), Omani
      (W616X), or Italian (958-1G > A) origins. Haplotype analysis demonstrated common
      ancestral mutant alleles for each mutation, apart from one of the six Pakistani
      families in which the mutation 676insC (which occurs in a repeat of seven
      cytosines) was present on a different genetic background. All mutations were
      homozygous, apart from the three UK Caucasian cases that were all compound
      heterozygotes (second allele mutations: L302X, 1161delA, 1909delA). All mutations
      were associated with markedly reduced or absent skin immunostaining with an
      antikindlin-1 antibody. These loss-of-function KIND1 mutations demonstrate the
      importance of kindlin-1 in maintaining epithelial integrity, although the
      mechanism linking this mutant protein to photosensitivity and poikiloderma
      remains to be determined. Delineation of these recurrent mutations is also
      relevant to optimizing mutation detection strategies in Kindler syndrome patients
      from particular ethnic backgrounds.

PMID- 14962094
TI  - A novel nonsense mutation in Kindler syndrome.

PMID- 14962095
TI  - Tumor necrosis factor-alpha and interferon-gamma polymorphisms contribute to
      susceptibility to oral lichen planus.
AB  - Most lymphocytes in the lamina propria of oral lichen planus (OLP) lesions
      express and secrete interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha
      (TNF-alpha), whereas they do not secret interleukin-4 and -10 or transforming
      growth factor-beta. We analyzed whether the polymorphisms of several cytokines
      may influence the susceptibility to OLP. Cytokine typing was performed by a
      sequence-specific PCR assay. Thirteen cytokine genes with 22 single-nucleotide
      polymorphisms were studied. IFN-gamma UTR 5644 genotype frequencies showed a
      significant increase in number of T/T homozygotes in OLP patients compared with
      controls (40.9 vs. 22.9%; p=0.0022). Moreover, in OLP patients, the frequency of
      the -308A TNF-alpha allele was higher than in the controls (21.6 vs. 9.3%; p <
      0.05) causing a significantly increased frequency of the genotype G/A in OLP
      (43.2 vs. 14.3%; p=0.0002). Because in patients with mucocutaneous lichen planus
      (LP), the frequency of the -308A TNF-alpha allele was more than double the values
      in the pure OLP patients (40.9 vs. 15.1%; p=0.003), the -308G/A TNF-alpha
      genotype showed a significantly higher frequency in patients with mucocutaneous
      LP than in patients with pure OLP (81.8 vs. 30.3%, p=0.003). In conclusion, we
      suggest that genetic polymorphism of the first intron of the promoter gene of IFN
      gamma may be an important risk factor to develop oral lesions of LP, whereas an
      increase in the frequency of -308A TNF-alpha allele may best contribute to the
      development of additional skin involvement.

PMID- 14962096
TI  - Differential expression and function of Toll-like receptors in Langerhans cells:
      comparison with splenic dendritic cells.
AB  - Toll-like receptors are key elements in pathogen recognition by the host immune
      system. Although the expression pattern and functions of Toll-like receptors have
      been studied in a variety of cytokine-induced dendritic cells, it remains unknown
      whether Toll-like receptor stimulation influences maturation and cytokine
      production of authentic Langerhans cells. We purified murine epidermal Langerhans
      cells along with splenic dendritic cell using a panning method. Langerhans cells
      expressed Toll-like receptor 2, 4, and 9 but not 7, the pattern of which suggests
      Langerhans cells are the closest to one of the murine dendritic cell lineage,
      CD11c+11b+8 alpha-4-. Then we stimulated Toll-like receptor 2, 4, and 9 with the
      corresponding ligand, Staphylococcus aureus Cowan 1, lipopolysaccharide, and CpG,
      and found that all of these stimuli upregulated expression of B7-1 and B7-2 in
      splenic dendritic cells but not in Langerhans cells. As in human Langerhans
      cells, stimulation of murine Langerhans cells with Staphylococcus aureus Cowan 1,
      lipopolysaccharide, and CpG overall resulted in T helper 1-polarizing cytokine
      production (namely, induction of IL-12p40 and inhibition of TARC (thymus and
      activation-regulated chemokine)/CCL17). Exceptionally, lipopolysaccharide
      exhibited no effect on IL-12p40 production by Langerhans cells and inhibited IL
      12p40 production by splenic dendritic cells. These results may represent the
      functional heterogeneity between Langerhans cells and splenic dendritic cells,
      and are important for better understanding of innate immunity to bacterial
      infections differentially regulated in the skin and spleen. MeSH terms: Toll-like
      receptors, Langerhans cells, dendritic cells.

PMID- 14962097
TI  - Characterization of the anti-BP180 autoantibody reactivity profile and epitope
      mapping in bullous pemphigoid patients.
AB  - Bullous pemphigoid is a subepidermal bullous disease of skin and mucosae
      associated with autoantibodies to BP180. To characterize the humoral response to
      BP180, we generated a random BP180 epitope library displayed on lambda
      bacteriophage. After validation of the library by epitope mapping of three BP180
      specific monoclonal antibodies, 15 novel or known BP180 epitopes were identified
      using 10 bullous pemphigoid serum samples. Fifty-seven bullous pemphigoid and 81
      control sera were then assayed against the selected epitopes. Thirty-one out of
      57 (54%) bullous pemphigoid sera reacted with at least an additional antigenic
      site other than the NC16A, within the extracellular (37%) and intracellular (28%)
      domains of BP180. In addition, the reactivity with extracellular epitopes of
      BP180 contained within the residue stretches 508-541 and 1331-1404 appeared to be
      related to the presence of both skin and mucosal involvement. Finally, a
      preliminary analysis of the epitope pattern in the disease course indicated that
      bullous pemphigoid patients exhibit a specific reactivity pattern, and that
      binding to intracellular epitopes of BP180, in addition to NC16A, may be
      detectable at an early clinical stage. Our findings provide novel insights into
      the pathophysiology of bullous pemphigoid and show the potential of the utilized
      approach as a tool for a rapid diagnosis of bullous pemphigoid patients and their
      management.

PMID- 14962098
TI  - Sezary syndrome cells unlike normal circulating T lymphocytes fail to migrate
      following engagement of NT1 receptor.
AB  - Circulating malignant Sezary cells are a clonal proliferation of CD4+CD45RO+ T
      lymphocytes primarily involving the skin. To study the biology of these malignant
      T lymphocytes, we tested their ability to migrate in chemotaxis assays.
      Previously, we had shown that the neuropeptide neurotensin (NT) binds to freshly
      isolated Sezary malignant cells and induces through NT1 receptors the cell
      migration of the cutaneous T cell lymphoma cell line Cou-L. Here, we report that
      peripheral blood Sezary cells as well as the Sezary cell line Pno fail to migrate
      in response to neurotensin although they are capable of migrating to the
      chemokine stromal-cell-derived factor 1 alpha. This is in contrast with normal
      circulating CD4+ or CD8+ lymphocytes, which respond to both types of
      chemoattractants except after ex vivo short-time anti-CD3 monoclonal antibody
      activation, which abrogates the neurotensin-induced lymphocyte migration.
      Furthermore, we demonstrate that neurotensin-responsive T lymphocytes express the
      functional NT1 receptor responsible for chemotaxis. In these cells, but not in
      Sezary cells, neurotensin induces recruitment of phosphatidylinositol-3 kinase,
      and redistribution of phosphorylated cytoplasmic tyrosine kinase focal adhesion
      kinase and filamentous actin. Taken together, these results, which show
      functional distinctions between normal circulating lymphocytes and Sezary
      syndrome cells, contribute to further understanding of the physiopathology of
      these atypical cells.

PMID- 14962099
TI  - Modulation of skin norepinephrine turnover by allergen sensitization: impact on
      contact hypersensitivity and T helper priming.
AB  - The information gathered by dendritic cells during the innate immune response is
      determinant for the type and strength of the adaptive response. We showed that
      the sympathetic neurotransmitter norepinephrine influences dendritic cell
      migration and T helper priming via alpha- and beta-adrenoceptors. Others have
      shown that Langerhans cells also express mRNA for beta 1-, beta 2-, and alpha 1A
      adrenoceptors and that catecholamines may inhibit the antigen-presenting
      capability via beta 2-adrenoceptors. Here we report that oxazolone, which induces
      a predominant T-helper-1-type contact hypersensitivity response, but not
      fluorescein isothiocyanate, which induces a prevailing T-helper-2-type response,
      inhibits the local norepinephrine turnover in the skin of mice during the first 8
      h of sensitization. Oxazolone also induced higher expression of the inflammatory
      cytokines interleukin-1 and interleukin-6 mRNA in the skin. Lack or blockade of
      these cytokines as well as inhibition of prostaglandin synthesis, however, did
      not influence the oxazolone effect. Only the nonspecific anti-inflammatory
      steroid dexamethasone could neutralize the effect of oxazolone. Furthermore,
      fluorescein isothiocyanate but not oxazolone sensitization in the presence of the
      specific beta 2-adrenoceptor antagonist ICI 118,551 enhanced the consequent
      contact hypersensitivity response as well as the production of T helper 1
      cytokines in draining lymph nodes; conversely T helper 2 cytokines were not
      affected. Thus, the extent of T helper 1 priming in the adaptive response to a
      sensitizing agent seems to depend also on its ability to modulate the local
      sympathetic nervous activity during the innate immune response.

PMID- 14962100
TI  - Arsenic induces human keratinocyte apoptosis by the FAS/FAS ligand pathway, which
      correlates with alterations in nuclear factor-kappa B and activator protein-1
      activity.
AB  - Epidemiologic studies demonstrated that long-term exposure to arsenic induces
      arsenical skin cancers, including Bowen's disease. Immunohistochemically, Bowen's
      disease shows proliferating and apoptotic characteristics. The transcription
      factors nuclear factor-kappa B (NF-kappa B) and activator protein-1 (AP-1)
      functionally regulate cell proliferation, transformation, and apoptosis. To
      investigate the mechanism of arsenic-induced apoptosis and related alterations in
      NF-kappa B and AP-1 activity, we exposed cultured human foreskin keratinocytes to
      different concentrations of sodium arsenite. At lower concentrations (< or =1
      microM), arsenic induced keratinocyte proliferation and enhanced both NF-kappa B
      and AP-1 activity. At higher concentrations (> or =5 microM), arsenic induced
      keratinocyte apoptosis by the Fas/Fas ligand (FasL) pathway. At apoptosis
      induction concentrations, NF-kappa B activity was not enhanced; however, AP-1
      activity was further enhanced. These results indicated that upregulation of NF
      kappa B at lower arsenic concentrations was correlated with keratinocyte
      proliferation. In contrast, higher concentrations of arsenic enhanced AP-1 and
      induced Fas/FasL-associated apoptosis. The concentration-dependent arsenic
      effects on transcription factors activity can help to clarify the mechanisms in
      arsenic-induced proliferation and apoptosis in keratinocytes.

PMID- 14962101
TI  - Rosiglitazone inhibits proliferation, motility, and matrix metalloproteinase
      production in keratinocytes.
AB  - This study was undertaken to evaluate the effects of thiazolidinediones (TZD) on
      keratinocyte proliferation, motility, and matrix metalloproteinase (MMP)
      production. Rosiglitazone (a potent TZD) inhibited both proliferation and
      motility as well as elaboration of MMP-1 and MMP-9. Inhibition was obtained with
      keratinocytes in monolayer culture and human skin in organ culture. There were
      significant concentration-response differences in sensitivity of the three
      keratinocyte responses to treatment with rosiglitazone. In contrast to
      keratinocytes, dermal fibroblasts were resistant to the effects of rosiglitazone.
      Treatment of keratinocytes with rosiglitazone did not suppress epidermal growth
      factor receptor autophosphorylation, but inhibited signaling through the
      extracellular regulated kinase mitogen-activated protein kinase pathway without a
      concomitant effect on pathways that lead to c-jun activation. Pioglitazone,
      another TZD, also suppressed keratinocyte proliferation, although it was less
      effective than rosiglitazone. An experimental TZD (BP-1107) inhibited
      keratinocyte proliferation at a much lower concentration than either
      rosiglitazone or pioglitazone. Because enhanced keratinocyte motility and
      increased MMP production as well as increased keratinocyte proliferation are
      thought to contribute to the phenotype of psoriatic lesional skin, we propose
      that interference with these keratinocyte responses contributes to the previously
      reported antipsoriatic activity of TZD.

PMID- 14962102
TI  - Association of cyclic adenosine monophosphate with permeability barrier
      homeostasis of murine skin.
AB  - Activation of Gs protein increases the intracellular cyclic adenosine
      monophosphate (cAMP) level, and the Gs protein-linked receptor has been
      implicated in the skin barrier homeostasis. In this study, we investigated the
      role of cAMP in epidermal barrier function. The barrier was disrupted by tape
      stripping or treatment with acetone. Immediately after barrier disruption,
      reagents affecting the cAMP level were topically applied. Topical application of
      forskolin, which activates cAMP synthesis delayed barrier recovery, whereas
      application of the antagonist of cAMP, cAMP-Rp, accelerated barrier recovery.
      Moreover, application of 9-cyclopentyladenine, an inhibitor of cAMP synthesis
      also accelerated barrier recovery. Tape stripping was found to increase the cAMP
      in the epidermis. Light and electron microscopic observations showed the delay of
      lamellar body secretion by forskolin and acceleration of the lamellar body
      secretion by cAMP-Rp. Application of an inhibitor of protein kinase A did not
      affect the barrier recovery rate. The delay of barrier recovery induced by
      forskolin was blocked by the voltage-gated calcium channel blockers, nifedipine
      and verapamil. In cultured keratinocytes, forskolin increased the intracellular
      calcium concentration and both nifedipine and verapamil blocked the increase.
      These results suggest that intracellular cAMP in the epidermis is involved in
      skin barrier homeostasis.

PMID- 14962103
TI  - Hair keratin associated proteins: characterization of a second high sulfur KAP
      gene domain on human chromosome 21.
AB  - Analysis of the EBI/GeneBank database using nonhuman hair keratin associated
      protein (KAP) gene sequences as a query resulted in the identification of two
      human KAP gene domains on chromosome 21, one of which, located at 21q22.1, has
      recently been characterized. The second domain presented here, an approximately
      90 kb domain on chromosome 21q23, harbored 16 KAP genes and two KAP pseudogenes.
      By comparison with known sheep and mouse KAP families, these genes could be
      assigned to two KAP families, KAP10 and KAP12, with the KAP10 family (12 members)
      being distinctly larger than the KAP12 family (four members). Systematic cDNA/3'
      rapid amplification of cDNA ends isolation studies using human scalp mRNA led to
      the identification of eight KAP10 and two KAP12 cDNA sequences. In situ
      hybridization analyses of human anagen hair follicles using specific 3'-noncoding
      sequences of the various KAP10/KAP12 genes revealed mRNA expression of nearly all
      KAP10 and KAP12 members exclusively in a narrow region of the middle portion of
      the hair fiber cuticle. Bioinformatic analyses of the promoter regions of the
      KAP10/KAP12 genes demonstrated several enhancer elements that were present in
      nearly all of the KAP genes. Primary among these were binding elements for the
      ETS, heat shock factor, AML, and HOX families of transcription factors.

PMID- 14962104
TI  - Topical application of a protein kinase C inhibitor reduces skin and hair
      pigmentation.
AB  - To determine whether inhibition of PKC-beta activity decreases pigmentation,
      paired cultures of primary human melanocytes were first pretreated with
      bisindolylmaleimide (Bis), a selective PKC inhibitor, or vehicle alone for 30
      min, and then treated with TPA for an additional 90 min to activate PKC in the
      presence of Bis. Bis blocked the expected induction of tyrosinase activity by
      activation of PKC. Addition of a peptide corresponding to amino acids 501-511 of
      tyrosinase containing its PKC-beta phosphorylation site, a presumptive PKC-beta
      pseudosubstrate, gave similar results. To determine whether Bis reduces
      pigmentation in vivo, the backs of four shaved and depilated pigmented guinea
      pigs were UV irradiated with a solar simulator for 2 wk excluding weekends.
      Compared to vehicle alone, Bis (300 microM), applied twice daily to paired sites
      for various periods encompassing the irradiation period, decreased tanning. Bis
      also, although less strikingly, reduced basal epidermal melanin when topically
      applied twice daily, 5 d per wk, for 3 wk to shaved and depilated unirradiated
      skin. Moreover, topical application of Bis (100 microM) once daily for 9 d to the
      freshly depilated backs of 8-wk-old mice markedly lightened the color of
      regrowing hair. These results demonstrate that inhibiting PKC activity in vivo
      selectively blocks tanning and reduces basal pigmentation in the epidermis and in
      anagen hair shafts.

PMID- 14962105
TI  - Membrane type-1 matrix metalloproteinase promotes human melanoma invasion and
      growth.
AB  - Membrane type-I metalloproteinase (MT1-MMP) is a transmembrane metalloproteinase
      that is critical for tumor cell invasion. MT1-MMP can degrade extracellular
      matrix (ECM) proteins directly and/or indirectly by activating soluble MMPs such
      as pro-MMP-2. Although MT1-MMP is upregulated in malignant melanoma, the
      biological consequences of elevated MT1-MMP expression for tumor progression are
      not entirely understood. In the current study, we have utilized the Bowes
      melanoma line for evaluating MT1-MMP in invasion and growth. Our studies extend
      the earlier observations to demonstrate that MT1-MMP expression in Bowes melanoma
      cells promotes selective invasion into matrigel but not matrices consisting of
      type-I collagen. Furthermore, MT1-MMP expressing melanoma cells exhibit increased
      migration in response to laminin 1 but not to type-I or type-IV collagen. MT1-MMP
      expression results in enhanced 3 dimensional growth in agarose gels and in long
      term cultures within matrigel. The hydroxymate inhibitor BB94 inhibits MT1-MMP
      enhanced invasion and growth in 3 dimensional culture systems, but had no effect
      on increased motility. We demonstrated that MT1-MMP expression significantly
      facilitated tumorigenicity and growth by intradermal injection. The results
      suggest a more general role for elevated MT1-MMP in promoting both the selective
      invasion and increased growth of malignant melanoma in vivo.

PMID- 14962106
TI  - Sheet preparations expose the dermal nerve plexus of human skin and render the
      dermal nerve end organ accessible to extensive analysis.
AB  - Since vertical tissue sections used for the study of the human cutaneous nervous
      system inherently allow visualization of only a small part of the mainly
      horizontally oriented cutaneous nerves, we searched for possibilities to extend
      this view. We now propose a method based on the immuno-staining of dermal sheet
      preparations for subsequent analysis by electron-, light- or laser scanning
      microscopy. Dermal sheet preparations for the first time allowed the imaging of
      the complex structure of the nerve end organ over several cm2, and facilitated
      viewing of its topological relationship to other tissue components. We could
      visualize that the bulk of free ending nerve fibers ramified within 25 microm of
      the dermo-epidermal junction, whereas below that only larger nerve bundles were
      present. This method further allowed the detection and quantification of
      NCAM/CD56+ non-myelinating Schwann cells which envelope terminal axons within the
      dermis. Depending on the body region, we detected between 140 to over 300
      individual terminal Schwann cells per mm2 skin surface. Our method should allow
      the acquisition of new insights into the highly organized architecture of the
      skin nerve end organ. Its further application will give new impetus in the
      investigation of alterations of this skin compartment under pathological
      conditions.

PMID- 14962107
TI  - Ultraviolet radiation-induced inflammation as a model for cutaneous hyperalgesia.
AB  - The effects of UVA-I and solar simulated radiation on skin sensitivity to thermal
      and mechanical stimuli were compared in normal volunteers. Individual minimal
      erythema doses (MED) for each source were determined and previously unexposed
      buttock skin was exposed to 1, 2 and 3 MED of each spectrum. Erythema, and
      mechanical and thermal pain thresholds were quantified from 3 to 72 hours post
      irradiation. Irradiated skin did not exhibit pain but hyperalgesia and allodynia
      were provoked by the applied stimuli after exposure to 2 or 3 MED. There were
      highly significant decreases in thresholds for both stimuli in exposed skin
      compared with non-exposed skin. These changes began within a few hours of
      irradiation, peaked about 24 hours later and persisted throughout the test
      period. The sensitivity changes broadly followed the erythema response and did
      not extend beyond the irradiated area. There were only minor differences between
      the two spectra at comparable erythemal doses. These data demonstrate the
      usefulness of UVR-induced inflammation as a model of cutaneous hypersensitivity.
      This model has clinical relevance for the study of hyperalgesia in general and
      the abnormal sensitivity of sunburnt skin in particular. It is likely to be
      useful in the assessment of peripherally acting analgesic drugs.

PMID- 14962108
TI  - The ultraviolet fingerprint dominates the mutational spectrum of the p53 and Ha
      ras genes in psoralen + ultraviolet A keratoses from psoriasis patients.
AB  - Psoriasis patients exposed to high cumulative doses of psoralen + ultraviolet A
      frequently exhibit so-called "psoralen + ultraviolet A keratoses" (i.e.,
      hyperkeratotic lesions with varying degrees of histologic atypia). The exact
      causes and molecular mechanisms of psoralen + ultraviolet A keratoses however,
      are not clear. We therefore performed DNA mutational analysis of the tumor
      suppressor gene p53 (exons in psoralen + ultraviolet A keratoses from 10 long
      term psoralen + ultraviolet A-treated psoriasis patients. We detected 39 p53
      mutations in 16 of 28 psoralen + ultraviolet A keratoses (57%) and 18 Ha-ras
      mutations in 11 of 25 psoralen + ultraviolet A keratoses (44%). Of the 39 p53
      mutations and 18 Ha-ras mutations, 22 (56%) and 13 (72%), respectively, were of
      the ultraviolet fingerprint type (C-->T or CC-->TT transitions at dipyrimidine
      sites); 13 (33%) and two (11%), respectively, occurred at potential psoralen
      binding sites (5'-TpA, 5'-TpG, or 5'-TpT DNA sequences) and were potentially
      psoralen + ultraviolet A induced; two (5%) and three (17%), respectively, were of
      ambiguous origin (ultraviolet and/or psoralen + ultraviolet A); and two (5%) and
      none (0%), respectively, were of the "other" type, respectively. We conclude that
      (1) the frequent mutation of p53 and Ha-ras may play a key part in the formation
      of at least some psoralen + ultraviolet A keratoses; (2) environmental and/or
      therapeutic ultraviolet exposure may be a major cause of psoralen + ultraviolet A
      keratosis as most Ha-ras and p53 mutations are induced by ultraviolet light; and
      (3) psoralen + ultraviolet A itself plays a smaller, though direct, role in
      causing these mutations.

PMID- 14962109
TI  - Ultraviolet B-induced skin angiogenesis is associated with a switch in the
      balance of vascular endothelial growth factor and thrombospondin-1 expression.
AB  - We have previously shown that targeted overexpression of the endogenous
      angiogenesis inhibitor thrombospondin-1 (TSP-1) in the epidermis prevented
      chronic ultraviolet B (UVB)-induced angiogenesis and cutaneous photodamage in
      mice, suggesting that angiogenesis plays a critical role in the mediation of UVB
      effects on the skin. Nevertheless, the molecular regulation of angiogenesis
      factors and inhibitors by acute UVB irradiation still remains to be elucidated.
      We performed quantitative analyses of cutaneous vascularity and of vascular
      endothelial growth factor (VEGF) and TSP-1 expression after acute UVB irradiation
      of mouse skin. Skin vascularity in the upper dermis was greatly increased until
      day 8 after a single dose of UVB irradiation (200 mJ per cm2) and associated with
      upregulation of VEGF mRNA expression, with downregulation of TSP-1 mRNA, and with
      protein expression in the hyperplastic epidermis. After 13 days, skin vascularity
      was normalized with downregulation of VEGF mRNA expression and upregulation of
      TSP-1 mRNA expression to the levels observed in non-UVB-irradiated skin. In
      contrast, the angiogenic UVB response was prolonged in TSP-1-deficient mice. We
      found a pronounced induction of the TSP-1 receptor CD36 in CD31-positive vessels
      on day 8 after UVB irradiation, associated with vascular endothelial cell
      apoptosis. These results demonstrate that acute UVB irradiation leads to a shift
      toward a proangiogenic environment and they suggest that the balance between VEGF
      and TSP-1 plays a critical role in the control of angiogenesis and vascular
      regression induced by acute UVB irradiation.

PMID- 14962110
TI  - Single-nucleotide polymorphisms of vascular endothelial growth factor in
      psoriasis of early onset.
AB  - Vascular endothelial growth factor (VEGF)--a stimulus of angiogenesis--is
      produced by epidermal keratinocytes, and elevated levels have been found in
      plaques of psoriasis. Polymorphisms in the VEGF gene regulate production of VEGF.
      We postulated that patients with psoriasis may have altered systemic expression
      of VEGF consequent upon programming at the genomic level. We investigated the
      genetic basis of VEGF expression in patients with type 1 (onset before age 40 y)
      chronic plaque psoriasis compared to healthy controls and also measured plasma
      levels of VEGF and its receptors flt-1 and KDR. Patients with severe disease, and
      those with onset of psoriasis between the ages of 20 and 40 y showed
      significantly increased frequency of the +405 CC genotype (p=0.04 and p=0.02) and
      the C allele (p=0.03 and p=0.02), respectively, compared to healthy controls.
      Plasma levels of VEGF and flt-1 were significantly detectable in patients with
      psoriasis compared with controls (p<0.001); by contrast, mean plasma levels of
      KDR in psoriatic patients were comparable with controls. These results suggest
      that alterations in the biology of VEGF may be involved in the pathogenesis of
      psoriasis. VEGF, flt-1, and KDR could provide attractive targets for future
      psoriasis therapy.

PMID- 14962111
TI  - Analysis of gene expression in fibroblasts in response to keratinocyte-derived
      factors in vitro: potential implications for the wound healing process.
AB  - Cocultures of fibroblasts and keratinocytes, physically separated by a membrane,
      were carried out for 48 h, and large-scale gene expression in the fibroblasts was
      analyzed by Affymetrix microarrays of expressed mRNAs. Two independent
      experiments were performed with cells from different individuals. A total of 243
      genes were upregulated twofold or more and 100 genes were negatively regulated
      (reduction by half or more) in both experiments. A total of 69 of these 343 genes
      coded for growth factors, cytokines, chemokines, or their receptors;
      extracellular matrix molecules or enzymes involved in their synthesis; adhesion
      receptors; proteinases/proteinase inhibitors or their receptors; cell cycle
      regulators; apoptosis-regulating factors; prostaglandin-related factors; or
      growth-factor-binding proteins. Most of the remaining genes coded for proteins
      involved in signal transduction or general metabolism. Sixteen genes selected
      from these groups were further analyzed by northern blot analysis to confirm the
      array data. Finally, experiments with interleukin-1 alpha (IL-1 alpha)-blocking
      antibodies or IL-1 receptor antagonists demonstrate that IL-1 alpha is one
      important factor involved in keratinocyte-mediated regulation of gene expression
      in fibroblasts. Taken together, the results suggest that keratinocytes regulate
      fibroblast gene expression with implications for the wound healing process during
      reepithelialization.

PMID- 14962112
TI  - Keratinocyte growth factor 1 inhibits wound edge epithelial cell apoptosis in
      vitro.
AB  - The ability of keratinocyte growth factor 1 to modulate apoptosis in the absence
      of proliferation was studied in vitro. A HaCaT scrape wound model was developed
      in which dense monolayers prior to wounding were cultured to quiescence in
      defined media with hydroxyurea at concentrations that blocked proliferation
      without loss of cell viability. Scrape wounding was then found to induce
      apoptosis, originating at the wound edge, but subsequently radiating away over a
      24 h period to encompass areas not originally damaged. Keratinocyte growth factor
      1 inhibited this radial progression of apoptosis in a concentration-dependent
      manner up to 20 ng per mL with induced migration present at the wound edge. The
      extent of this rescue was modulated by the concentration of Ca2+ prior to
      wounding. In control wound cultures apoptotic bodies were found in cells adjacent
      to the wound interface but were greatly reduced in keratinocyte-growth-factor-1
      treated groups. Keratinocyte growth factor 1 receptor expression was
      significantly induced within two to three cell widths of the scraped wound edge,
      at levels far exceeding those found at the leading edge of a nonwounded
      epithelial sheet. Tumor necrosis factor alpha (1-5 ng per mL) or Escherichia coli
      lipopolysaccharide (10-50 ng per mL) exacerbated scrape-induced early apoptosis
      (1-4 h), but was largely ameliorated by coculture with keratinocyte growth factor
      1. Keratinocyte growth factor 1 protection was associated with a reduction in
      both caspase-3 activation and cytokeratin-19 loss. Protected wound edges were
      also associated with the maintenance of e-cadherin expression and induction of
      beta1 integrin and actin stress fiber organization. These results suggest that
      keratinocyte growth factor 1 may play a role in limiting mechanically induced
      apoptotic processes at the epithelial wound edge in a manner that is distinct
      from its proliferative function.

PMID- 14962113
TI  - Krt6a-Cre transgenic mice direct LoxP-mediated recombination to the companion
      cell layer of the hair follicle and following induction by retinoic acid to the
      interfollicular epidermis.

PMID- 14962114
TI  - The human hair bulb is a source and target of CRH.

PMID- 14962116
TI  - In this issue: The complexities of epidermolysis bullosa "simplex".

PMID- 14962118
TI  - Keratinocyte heal thyself: a new form of "natural gene therapy".

PMID- 14962119
TI  - Roads to the edge of the cell: Intracellular transport of cornified envelope
      precursors.

PMID- 14962120
TI  - Evidence for vascular endothelial growth factor (VEGF) as a modifier gene in
      psoriasis.

PMID- 14962121
TI  - Strategies for the detection of Escherichia coli O157:H7 in foods.

PMID- 14962122
TI  - Efficiency of chlorocatechol metabolism in natural and constructed chlorobenzoate
      and chlorobiphenyl degraders.
AB  - AIMS: A possibility for the complementation of both ortho- and meta-cleavage
      pathway for chlorocatechols in one strain and its impact on degradation of
      chlorobenzoates accumulated during degradation of polychlorinated biphenyls was
      investigated. METHODS AND RESULTS: Genes responsible for ortho-cleavage of
      chlorocatechols were subcloned into two biphenyl degraders and the activities of
      chlorocatechol dioxygenases responsible for ortho- and meta-cleavage in these
      hybrid strains were monitored spectrophotometrically and also electrochemically
      by ion-selective electrode. CONCLUSIONS: While strain Pseudomonas fluorescens
      S12/C apparently gained metabolic advantage from this gene manipulation, strain
      Burkholderia cepacia P166/C did not express better degradation features in
      comparison with the parental strain. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      approach has the potential to enhance chlorocatechol metabolism in selected
      biphenyl degraders.

PMID- 14962123
TI  - The use of a marked strain of Pseudomonas fluorescens to model the spread of
      brain tissue to the musculature of cattle after shooting with a captive bolt gun.
AB  - AIMS: The aim of this study was to use a marked strain of Pseudomonas fluorescens
      to model the spread of central nervous system (CNS) tissue in cattle following
      captive bolt stunning. METHODS AND RESULTS: The marked organism was introduced by
      injection through the captive bolt aperture immediately after stunning and was
      subsequently detected in a wide range of derived tissues, including blood,
      organs, and the musculature of the entire forequarters of test animals. This was
      dependent on the use of high concentrations of the organism that were recovered
      sufficiently and rapidly to minimize the bactericidal properties of the
      circulatory system. These results suggest that a marked organism could
      potentially be used to model the effects of captive bolt stunning on the
      dissemination of CNS tissue from the brain. CONCLUSIONS: These results indicate
      that current commercial methods of captive bolt stunning may induce widespread
      and significant mobilization of CNS tissue within beef carcasses. This may lead
      to the widespread dissemination of such materials within meat destined for human
      consumption. SIGNIFICANCE AND IMPACT OF THE STUDY: In the absence of rapid,
      simple and sufficiently sensitive methods for the direct detection of prion in
      commercially slaughtered animals, marked organisms can provide useful models in
      studies of the dissemination kinetics of prion disease in captive bolt stunned
      animals.

PMID- 14962124
TI  - Evaluation of a RAPD-based typing scheme in a molecular epidemiology study of
      Vibrio cholerae O1, Brazil.
AB  - AIMS: To evaluate the utility of random amplification of polymorphic DNA (RAPD)
      technique for routine practice in public health laboratories for epidemiological
      studies of Vibrio cholerae O1 isolates. MATERIALS AND RESULTS: Seventy-nine
      strains were examined by PCR for the toxin genes (ctx A, zot and ace), virulence
      associated genes (tcp A and tox T) and RAPD sequences. Except for one strain (no.
      1123) from the Amazonas State, all the strains analysed carried the genes ctx A,
      zot, ace, tcp A and tox T. RAPD fingerprinting revealed variability but no
      correlation with serotype, biotype or geographical origin of the isolates was
      found. CONCLUSION: A standardized RAPD method does not enable the establishment
      of a pattern data bank for the identification of V. cholerae O1 strains.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The simplicity and discriminative capacity
      of this technique make it useful for detecting genetic diversity among micro
      organisms from a defined group or for outbreak investigation.

PMID- 14962125
TI  - Immigration and emigration of Burkholderia cepacia and Pseudomonas aeruginosa
      between and within mixed biofilm communities.
AB  - AIMS: To investigate the dynamics of binary culture biofilm formation through use
      of both the Sorbarod model of biofilm growth and the constant depth film
      fermenter (CDFF). METHODS AND RESULTS: Pseudo steady-state biofilm cultures of
      laboratory and clinical strains of Pseudomonas aeruginosa, selected on the basis
      of their ability to produce a Burkholderia cepacia growth-inhibitory substance,
      were established on Sorbarod filters and challenged with corresponding planktonic
      grown cultures of B. cepacia. Reverse challenges were also conducted. Both B.
      cepacia and P. aeruginosa were able to form steady-state monoculture biofilms
      after 48 h growth. When steady-state biofilms of B. cepacia NTCT 10661 were
      challenged with planktonically grown P. aeruginosa PAO1 known to produce a B.
      cepacia growth-inhibitory substance, the immigrant population was rapidly and
      almost completely bound to the biofilm, displacing B. cepacia. By contrast,
      established biofilms of P. aeruginosa PAO1 resisted immigration of B. cepacia
      10661. Similar experiments conducted with a nongrowth inhibitory substance
      producing clinical pairing of P. aeruginosa 313113 and B. cepacia 313113 led to
      the formation of stable, mixed biofilm populations in both instances. Moreover,
      co-inoculation with these clinical isolates resulted in a stable, mixed steady
      state biofilm. Similar observations were made for biofilms generated in CDFFs. In
      such instances following pan-swapping between two monoculture CDFFs, B. cepacia
      313113 was able to integrate into an established P. aeruginosa 313113 biofilm to
      form a stable binary biofilm. CONCLUSIONS: Establishment of a mixed species
      community follows a specific sequence of inoculation that may either be due to
      some degree of match between co-colonizers or that P. aeruginosa predisposes
      uncolonized sections of the surface to permit B. cepacia colonization.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Colonization of a surface with one
      bacterial species confers colonization resistance towards other species.
      Disinfection of a surface might well increase the probability of pathogen
      harbourage.

PMID- 14962126
TI  - Inactivation of indicator micro-organisms from various sources of faecal
      contamination in seawater and freshwater.
AB  - AIM: The survival of indicator micro-organisms in aquatic systems is affected by
      both biotic and abiotic factors. Much of the past research on this topic has been
      conducted using laboratory-generated cultures of indicator bacteria. For this
      study, we used natural sources of faecal contamination as inoculants into
      environmental water samples, thereby representing the wide diversity of organisms
      likely to be found in faecal contamination. METHODS AND RESULTS: Rates of
      inactivation of water quality indicators, total coliforms (TC), Escherichia coli,
      enterococci (EC) and F+-specific coliphage were studied in three experiments
      using inoculants of sewage influent, sewage effluent and urban storm drain run
      off. Effects of temperature, nutrients, total suspended solids, bacterial load
      and solar irradiation were studied in fresh and seawater matrices. Results
      demonstrated that temperature and solar irradiation had significant effects upon
      rates of inactivation (anova, P < 0.001). Inactivation rates were similar,
      regardless of the inoculant type. EC degraded the slowest in the dark with T90s
      of 115-121 and 144-177 h at 20 and 14 degrees C, respectively. When incubated in
      sunlight, EC was inactivated significantly more rapidly than either E. coli or F+
      specific coliphage (P < 0.001). CONCLUSIONS: Inactivation of indicator bacteria
      is not dependent upon the original source of contamination. Inactivation rates of
      indicator bacteria were similar in fresh and seawater matrices. However, EC
      degraded more rapidly in sunlight than E. coli. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study suggests that the source of faecal contamination is not an
      important factor to inactivation rates of indicator bacteria. However, rates of
      inactivation of indicator bacteria are likely system specific.

PMID- 14962127
TI  - Screening plant growth-promoting rhizobacteria for improving growth and yield of
      wheat.
AB  - AIMS: Plant growth promoting rhizobacteria (PGPR) are commonly used as inoculants
      for improving the growth and yield of agricultural crops, however screening for
      the selection of effective PGPR strains is very critical. This study focuses on
      the screening of effective PGPR strains on the basis of their potential for in
      vitro auxin production and plant growth promoting activity under gnotobiotic
      conditions. METHODS AND RESULTS: A large number of bacteria were isolated from
      the rhizosphere soil of wheat plants grown at different sites. Thirty isolates
      showing prolific growth on agar medium were selected and evaluated for their
      potential to produce auxins in vitro. Colorimetric analysis showed variable
      amount of auxins (ranging from 1.1 to 12.1 mg l-1) produced by the rhizobacteria
      in vitro and amendment of the culture media with l-tryptophan (l-TRP), further
      stimulated auxin biosynthesis (ranging from 1.8 to 24.8 mg l-1). HPLC analysis
      confirmed the presence of indole acetic acid (IAA) and indole acetamide (IAM) as
      the major auxins in the culture filtrates of these rhizobacteria. A series of
      laboratory experiments conducted on two cv. of wheat under gnotobiotic (axenic)
      conditions demonstrated increases in root elongation (up to 17.3%), root dry
      weight (up to 13.5%), shoot elongation (up to 37.7%) and shoot dry weight (up to
      36.3%) of inoculated wheat seedlings. Linear positive correlation (r = 0.99)
      between in vitro auxin production and increase in growth parameters of inoculated
      seeds was found. Based upon auxin biosynthesis and growth-promoting activity,
      four isolates were selected and designated as plant growth-promoting
      rhizobacteria (PGPR). Auxin biosynthesis in sterilized vs nonsterilized soil
      inoculated with selected PGPR was also monitored that revealed superiority of the
      selected PGPR over indigenous microflora. Peat-based seed inoculation with
      selected PGPR isolates exhibited stimulatory effects on grain yields of tested
      wheat cv. in pot (up to 14.7% increase over control) and field experiments (up to
      27.5% increase over control); however, the response varied with cv. and PGPR
      strains. CONCLUSIONS: It was concluded that the strain, which produced the
      highest amount of auxins in nonsterilized soil, also caused maximum increase in
      growth and yield of both the wheat cv. SIGNIFICANCE AND IMPACT OF STUDY: This
      study suggested that potential for auxin biosynthesis by rhizobacteria could be
      used as a tool for the screening of effective PGPR strains.

PMID- 14962128
TI  - Evaluation of bacterial communities belonging to natural whey starters for Grana
      Padano cheese by length heterogeneity-PCR.
AB  - AIMS: To detect bacteria present in controlled dairy ecosystems with defined
      composition by length-heterogeneity (LH)-PCR. LH-PCR allows to distinguish
      different organisms on the basis of natural variations in the length of 16S rRNA
      gene sequences. METHODS AND RESULTS: LH-PCR was applied to depict population
      structure of the lactic acid bacteria (LAB) species recoverable from Grana Padano
      cheese whey starters. Typical bacterial species present in the LAB community were
      evidenced and well discriminated. Small differences in species composition, e.g.
      the frequent finding of Streptococcus thermophilus and the constant presence of
      thermophilic lactobacilli (Lactobacillus helveticus, Lact. delbrueckii subsp.
      lactis/bulgaricus and Lact. fermentum) were reliably highlighted. Specificity of
      LH-PCR was confirmed by species-specific PCR from total DNA of the cultures.
      CONCLUSIONS: LH-PCR is a useful tool to monitor microbial composition and
      population dynamics in dairy starter cultures. When present, non-dominant
      bacterial species present in the whey starters, such as Strep. thermophilus, can
      easily be visualized and characterized without isolating and cultivating single
      strains. A similar approach can be applied to more complex dairy ecosystems such
      as milk or cheese curd. SIGNIFICANCE AND IMPACT OF THE STUDY: Community members
      and differences in population structure of controlled dairy ecosystems such as
      whey starters for hard cheeses can be evaluated and compared in a relative easy,
      fast, reliable and highly reproducible way.

PMID- 14962129
TI  - In vitro water activity and pH dependence of mycelial growth and extracellular
      enzyme activities of Trichoderma strains with biocontrol potential.
AB  - AIMS: Water activity (aw) and pH are probably the most important environmental
      parameters affecting the activities of mycoparasitic Trichoderma strains.
      Therefore it is important to collect information on the effects of these factors
      on mycelial growth and on the in vitro activities of extracellular enzymes
      involved in nutrient competition (e.g. beta-glucosidase, cellobiohydrolase and
      beta-xylosidase) and mycoparasitism (e.g. N-acetyl-beta-glucosaminidase, trypsin
      like protease and chymotrypsin-like protease) of Trichoderma strains with
      biocontrol potential. METHODS AND RESULTS: Water activity and pH dependence of
      the linear mycelial growth of five examined Trichoderma strains belonging to
      three different species groups was examined on yeast extract and soil extract
      media. Maximal growth rates were observed at aw 0.997 and pH 4.0 in the case of
      all strains. The activities of the examined extracellular enzymes at different aw
      and pH values were determined spectrophotometrically after incubation with
      chromogenic p-nitrophenyl and p-nitroaniline substrates. Maximal enzyme
      activities were measured at aw 0.950 for beta-glucosidase, trypsin-like protease
      and chymotrypsin-like protease, at 0.910 for cellobiohydrolase and at 0.993 for
      beta-xylosidase and N-acetyl-beta-glucosaminidase enzymes. Optimal pH values are
      suggested to be at 5.0 for beta-glucosidase, cellobiohydrolase and N-acetyl-beta
      glucosaminidase, at 3.0 for beta-xylosidase, at 6.0 for trypsin-like protease and
      between 6.0 and 7.0 for chymotrypsin-like protease activities, respectively.
      CONCLUSIONS: Extracellular enzymes of the examined mycoparasitic Trichoderma
      strains are able to display activities under a wider range of aw and pH values
      than those allowing mycelial growth. SIGNIFICANCE AND IMPACT OF THE STUDY: Data
      about the effects of aw and pH on mycelial growth and extracellular enzyme
      activities of Trichoderma reveal useful information about the applicability of
      biocontrol strains in agricultural soils with specific water and pH relations.

PMID- 14962130
TI  - Microbiological examination of ready-to-eat cold sliced meats and pate from
      catering and retail premises in the UK.
AB  - AIMS: To establish the microbiological quality of cold ready-to-eat sliced meats
      and pate from catering and retail premises, and investigate links hypothesized
      between foodborne Campylobacter infection and the consumption of cold sliced
      meats. METHODS AND RESULTS: A total of 4078 cold meat and pate samples were
      collected and examined according to a standardized protocol. Comparison with
      published microbiological guidelines revealed that most ready-to-eat meat and
      pate samples (75%) were of satisfactory/acceptable microbiological quality and
      25% were of unsatisfactory/unacceptable quality. Two cold meat samples (<1%) were
      of unacceptable microbiological quality because of the presence of Campylobacter
      jejuni in 25 g and Listeria monocytogenes at 3.4 x 104 CFU g-1. CONCLUSIONS:
      Acceptable microbiological quality was associated with premises where the
      management was trained in food hygiene and those that had hazard analysis in
      place. Poor microbiological quality was associated with storage above 8 degrees
      C, presliced meats, infrequent cleaning of slicing equipment and poor control of
      practices that may lead to cross contamination. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study provides important information about the microbiological
      quality of cold ready-to-eat meats and pate. It also assists caterers, retailers,
      enforcement officers and policy makers to understand how different food safety
      practices affect microbiological quality.

PMID- 14962131
TI  - Bioremediation of creosote-contaminated soil in South Africa by landfarming.
AB  - AIMS: To determine the combined effects of biostimulation and bioaugmentation in
      the landfarming of a mispah form (lithosol; food and Agriculture Organisation
      (FAO)) soil contaminated with >310000 mg kg-1 creosote with a view to developing
      a bioremediation technology for soils heavily contaminated with creosote. METHODS
      AND RESULTS: The excavated soil was mixed with 2500 kg ha-1 dolomitic lime and
      2000 kg ha-1 mono-ammonium phosphate (MAP) before spreading over a treatment bed
      of shale reinforced with clay. Sewage sludge (500 kg) was ploughed into 450 m3 of
      contaminated soil in the second and sixth months of treatment. A further 1000 kg
      ha-1 MAP was added to the soil at the end of the fifth month. Moisture was
      maintained at 70% field capacity. Total creosote was determined by the US
      Environmental Protection Agency (EPA) method 418.1 and concentrations of selected
      creosote components were determined by gas chromatography/flame ionisation
      detection (GC/FID). Total creosote was reduced by more than 90% by the 10th month
      of landfarming. The rate of reduction in creosote concentration was highest after
      the addition of sewage sludge. The three-ring PAHs were more slowly removed than
      naphthalene and the phenolic compounds. The four- and five-ring PAHs, although
      persist until the end of treatment, were reduced by 76-87% at the end of the
      experiment. CONCLUSIONS: A combination of biostimulation and bioaugmentation
      during landfarming could enhance the bioremediation of soils heavily contaminated
      with creosote. SIGNIFICANCE AND IMPACT OF THE STUDY: The study provides
      information on the management of a combination of biostimulation and
      bioaugmentation during landfarming, and contributes to the knowledge and database
      necessary for the development of a technology for bioremediating creosote
      contaminated land.

PMID- 14962132
TI  - Characterization of bacteriocin-like inhibitory substances (BLIS) from sourdough
      lactic acid bacteria and evaluation of their in vitro and in situ activity.
AB  - AIMS: To identify and characterize bacteriocion-producing lactic acid bacteria
      (LAB) in sourdoughs and to compare in vitro and in situ bacteriocin activity of
      sourdough- and nonsourdough LAB. METHODS AND RESULTS: Production of antimicrobial
      compounds by 437 Lactobacillus strains isolated from 70 sourdoughs was
      investigated. Five strains (Lactobacillus pentosus 2MF8 and 8CF, Lb. plantarum
      4DE and 3DM and Lactobacillus spp. CS1) were found to produce distinct
      bacteriocin-like inhibitory substances (BLIS). BLIS-producing Lactococcus lactis
      isolated from raw barley showed a wider inhibitory spectrum than sourdough LAB,
      but they did not inhibit all strains of the key sourdough bacterium Lb.
      sanfranciscensis. Antimicrobial production by Lb. pentosus 2MF8 and Lc. lactis
      M30 was also demonstrated in situ. CONCLUSIONS: BLIS production by sourdough LAB
      appears to occur at a low frequency, showing limited inhibitory spectrum when
      compared with BLIS-producing Lc. lactis. Nevertheless, they are active BLIS
      producers under sourdough and bread-making conditions. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The activity of BLIS has been demonstrated in situ. It may influence
      the complex sourdough microflora and support the implantation and stability of
      selected insensitive bacteria, such as Lb. sanfranciscensis, useful to confer
      good characteristics to the dough.

PMID- 14962133
TI  - Characterization of atypical Erwinia carotovora strains causing blackleg of
      potato in Brazil.
AB  - AIMS: To determine the characteristics of bacteria associated with the blackleg
      disease of potato in Brazil and compare them with species and subspecies of
      pectolytic Erwinia. METHODS AND RESULTS: Biochemical and physiological
      characteristics of 16 strains from blackleg-infected potatoes in State of Rio
      Grande do Sul, Brazil, were determined and differentiated them from all the E.
      carotovora subspecies and E. chrysanthemi. Pathogenicity and maceration ability
      of the Brazilian strains were greater than those of E. carotovora subsp.
      atroseptica, the causal agent of potato blackleg in temperate zones. Analyses of
      serological reaction and fatty acid composition confirmed that the Brazilian
      strains differed from E. carotovora subsp. atroseptica, but the sequence of 16S
      rDNA gene and the 16S-23S intergenic spacer (IGS) region confirmed the Brazilian
      strains as pectolytic Erwinia. Restriction analysis of the IGS region
      differentiated the Brazilian strains from the subspecies of E. carotovora and
      from E. chrysanthemi. A unique SexAI restriction site in the IGS region was used
      as the basis for a primer to specifically amplify DNA from the Brazilian potato
      blackleg bacterium in PCR. CONCLUSIONS: The bacterium that causes the blackleg
      disease of potato in Brazil differs from E. carotovora subsp. atroseptica, the
      blackleg pathogen in temperate zones. It also differs from other subspecies of E.
      carotovora and from E. chrysanthemi and warrants status as a new subspecies,
      which would be appropriately named E. carotovora subsp. brasiliensis.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The blackleg disease of potato is caused by
      a different strain of pectolytic Erwinia in Brazil than in temperate potato
      growing regions. The Brazilian strain is more virulent than E. carotovora subsp.
      atroseptica, the usual causal agent of potato blackleg.

PMID- 14962134
TI  - A nested-PCR assay for detection of Xylella fastidiosa in citrus plants and
      sharpshooter leafhoppers.
AB  - AIMS: Detection of Xylella fastidiosa in citrus plants and insect vectors.
      METHODS AND RESULTS: Chelex 100 resin matrix was successfully standardized
      allowing a fast DNA extraction of X. fastidiosa. An amplicon of 500 bp was
      observed in samples of citrus leaf and citrus xylem extract, with and without
      symptoms of citrus variegated chlorosis, using PCR with a specific primer set
      indicating the presence of X. fastidiosa. The addition of insoluble acid-washed
      polyvinylpyrrolidone (PVPP) prior to DNA extraction of insect samples using
      Chelex 100 resin together with nested-PCR permitted the detection of X.
      fastidiosa within sharpshooter heads with great sensitivity. It was possible to
      detect up to two bacteria per reaction. From 250 sharpshooter samples comprising
      four species (Dilobopterus costalimai, Oncometopia facialis, Bucephalogonia
      xanthopis and Acrogonia sp.), 87 individuals showed positive results for X.
      fastidiosa in a nested-PCR assay. CONCLUSIONS: The use of Chelex 100 resin
      allowed a fast and efficient DNA extraction to be used in the detection of X.
      fastidiosa in citrus plants and insect vectors by PCR and nested-PCR assays,
      respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: The employment of efficient
      and sensitive methods to detect X. fastidiosa in citrus plants and insect vectors
      will greatly assist epidemiological studies.

PMID- 14962135
TI  - Modulation of anti-pathogenic activity in canine-derived Lactobacillus species by
      carbohydrate growth substrate.
AB  - AIMS: To investigate the effect of various carbon sources on the production of
      extracellular antagonistic compounds against two Escherichia coli strains and
      Salmonella enterica serotype Typhimurium by three canine-derived lactobacilli
      strains. METHODS AND MATERIALS: Cell-free preparations, pH neutralized, were used
      in antibiotic disc experiments as an initial screening. The bacteria/carbohydrate
      combinations that showed inhibition of the growth of those pathogens, were
      further investigated in batch co-culture experiments. The cell-free supernatants
      of the cultures, that decreased the population number of the pathogens in the co
      culture experiments to log CFU ml-1 <or= 4, were tested for inhibition of the
      pathogens in pure cultures at neutral and acidic pH. CONCLUSIONS: The results
      showed that the substrate seems to affect the production of antimicrobial
      compounds and this effect could not just be ascribed to the ability of the
      bacteria to grow in the various carbon sources. L. mucosae, L. acidophilus and L.
      reuteri, when grown in sugar mixtures consisting of alpha-glucosides (Degree of
      Polymerization (DP) 1-4) could produce antimicrobial compounds active against all
      three pathogens in vitro. This effect could not be attributed to a single
      ingredient of those sugar mixtures and was synergistic. This inhibition had a
      dose-response characteristic and was more active at acidic pH. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Knowledge of the effect that the carbon source has on the
      production of antimicrobial compounds by gut-associated lactobacilli allows the
      rational design of prebiotic/probiotic combinations to combat gastrointestinal
      pathogens.

PMID- 14962136
TI  - Identification of the culturable and nonculturable bacterial population in ground
      water of a municipal water supply in Germany.
AB  - AIMS: The identification of the culturable and nonculturable bacterial population
      in ground water of a municipal water supply in Mainz (Germany) during the year
      2002. METHODS AND RESULTS: Total counts varied between 3.5 x 103 and 2.2 x 104
      cells ml-1, viable counts were approximately between 8.1 x 102 and 3.3 x 103
      cells ml-1. After cultivation on different nutrient media (R2A, DEV, PCA, Endo,
      Standard) <1% appeared to be culturable on the media used. After denaturating
      gradient gel electrophoreses, up to 24 different bacterial species were detected
      in the ground water. With the aid of 16S rDNA isolation, amplification and
      sequencing, the isolated organisms and clones could be identified. CONCLUSIONS:
      The isolated and cultured organisms mainly belonged to the Proteobacteria (alpha,
      beta and gamma), Flavobacteria or Actinobacteria. However, most of the
      noncultured micro-organisms were beta-Proteobacteria. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This is the first study in which the identification of all culturable
      and nonculturable bacteria in a ground water has been attempted.

PMID- 14962137
TI  - Engineering of quorum-sensing systems for improved production of alkaline
      protease by Bacillus subtilis.
AB  - AIM: Engineering of Rap-Phr quorum-sensing systems of Bacillus subtilis and
      subsequent evaluation of the transcription of the aprE gene, encoding a major
      extracellular alkaline protease. METHODS AND RESULTS: Addition of synthetic Phr
      pentapeptides to the growth medium, or overproduction of pre-Phr peptides,
      slightly improved the transcription of the aprE gene in B. subtilis. Disruption
      of certain rap genes similarly improved the transcription of the aprE gene. The
      production of extracellular proteolytic enzymes was increased when the rapA
      mutation was combined with a degU32 (Hy) mutation for hyper-secretion.
      CONCLUSIONS: Certain Rap-Phr systems of B. subtilis seem to suppress
      extracellular AprE production. Although this may be an important feature under
      natural conditions, repression of AprE production by these systems is not
      desirable under fermentation conditions. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Although the levels of aprE transcriptional increase in this study are moderate,
      engineering of Rap-Phr systems may be used to improve the yield of Bacillus
      strains that are used for the production of the extracellular protease AprE, or
      Bacillus strains that use of the aprE promoter for the production of a
      heterologous protein.

PMID- 14962138
TI  - Internal transcribed spacer 2 amplicon as a molecular marker for identification
      of Peronospora parasitica (crucifer downy mildew).
AB  - AIMS: The purpose of the study was to characterize the internal transcribed
      spacer (ITS) regions of Peronospora parasitica (crucifer downy mildew) in order
      to evaluate their potential as molecular markers for pathogen identification.
      METHODS AND RESULTS: PCR amplification of ribosomal RNA gene block (rDNA) spacers
      (ITS1 and ITS2) performed in 44 P. parasitica isolates from different Brassica
      oleracea cultivars and distinct geographic origins, revealed no length
      polymorphisms. ITS restriction analysis with three endonucleases, confirmed by
      sequencing, showed no fragment length polymorphisms among isolates. Furthermore,
      ITS amplification with DNA isolated from infected host tissues also allowed the
      detection of the fungus in incompatible interactions. The combination of the
      universal ITS4 and ITS5 primers, for amplification of full ITS, with a new
      specific forward internal primer for ITS2 (PpITS2F), originates a P. parasitica
      specific amplicon, suitable for diagnosis. CONCLUSIONS: As ITS2 regions of P.
      parasitica, B. oleracea, other B. oleracea fungal pathogens and other Peronospora
      species are clearly distinct, a fast and reliable molecular identification method
      based on multiplex PCR amplification of full ITS and P. parasitica ITS2 is
      proposed for the diagnosis of crucifer downy mildew. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The method can be applied to diagnose the disease in the absence of
      fungal reproductive structures, thus being useful to detect nonsporulating
      interactions, early stages of infection on seedlings, and infected young leaves
      packed in sealed plastic bags. Screening of seed stocks in sanitary control is
      also a major application of this diagnostic method.

PMID- 14962139
TI  - Monoacylglycerols: glycolipid biosurfactants produced by a thermotolerant yeast,
      Candida ishiwadae.
AB  - AIMS: To isolate and characterize biosurfactants produced by a thermotolerant
      yeast isolated in Thailand. MATERIALS AND RESULTS: Yeast strains isolated from
      plant material in Thailand were first screened for the ability to produce lipase
      and biosurfactant. A strain Y12, identified as Candida ishiwadae by physiological
      tests, survived at 45 degrees C and produced relatively large amounts of
      biosurfactants. From the culture filtrate of this strain, two glycolipid
      biosurfactants, a and b, were purified by solvent fractionation, silica gel and
      ODS column chromatographies. Compounds a and b were determined to be
      monoacylglycerols; 1-linoleylglycerol and 1-oleylglycerol, respectively. Both
      compounds exhibited higher surfactant activities tested by the drop collapse test
      than several artificial surfactants such as sodium dodecyl sulphate. CONCLUSIONS:
      Glycolipid biosurfactants produced by a thermotolerant yeast, C. ishiwadae were
      characterized to be monoacylglycerols which exhibited high surfactant activities.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A thermotolerant yeast strain, C.
      ishiwadae, could be a potential candidate for producing monoacylglycerols which
      are useful in industrial applications.

PMID- 14962140
TI  - Purification and characterization of a branched-chain amino acid aminotransferase
      from Lactobacillus paracasei subsp. paracasei CHCC 2115.
AB  - AIM: Purification and characterization of an aminotransferase (AT) specific for
      the degradation of branched-chain amino acids from Lactobacillus paracasei subsp.
      paracasei CHCC 2115. METHODS AND RESULTS: The purification protocol consisted of
      anion exchange chromatography, affinity chromatography and hydrophobic
      interaction chromatography. The enzyme was found to exist as a monomer with a
      molecular mass of 40-50 kDa. The AT converted isoleucine, leucine and valine at a
      similar rate with alpha-ketoglutarate as the amino group acceptor; minor activity
      was shown for methionine. The enzyme had pH and temperature optima of 7.3 and 43
      degrees C, respectively, and activity was detected at the pH and salt conditions
      found in cheese (pH 5.2, 4% NaCl). Hg2+ completely inhibited the enzyme, and the
      inhibition pattern was similar to that for pyridoxal-5'-phosphate-dependent
      enzymes, when studying the effect of other metal ions, thiol- and carbonyl
      binding agents. The N-terminal sequence of the enzyme was
      SVNIDWNNLGFDYMQLPYRYVAHXKDGVXD, and had at the amino acid level, 60 and 53%
      identity to a branched-chain amino acid AT of Lact. plantarum and Lactococcus
      lactis, respectively. CONCLUSIONS: The results suggest that Lact. paracasei
      subsp. paracasei CHCC 2115 may contribute to development of flavour in cheese.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of this work contribute to the
      knowledge of transamination performed by cheese-related bacteria, and in the
      understanding and control of amino acid catabolism and the production of aroma
      compounds.

PMID- 14962141
TI  - Adaptative responses in yeast to the herbicide 2-methyl-4-chlorophenoxyacetic
      acid at the level of intracellular pH homeostasis.
AB  - AIMS: The objective of this work was to examine adaptative responses occurring in
      Saccharomyces cerevisiae following exposure to the herbicide 2-methyl-4
      chlorophenoxyacetic acid (MCPA). METHODS AND RESULTS: The exposure of a yeast
      cell population to MCPA concentrations of moderate toxicity led to a period of
      latency before eventual resumption of inhibited growth. During this period of
      adaptation, the plasma membrane (PM) H+-ATPase was activated, in coordination
      with the decrease of intracellular pH (pHi), cell viability and average cell
      volume. The in vivo activation of this ATPase was demonstrated either by assaying
      PM-ATPase activity in membrane suspensions extracted from cells grown in the
      presence or absence of MCPA or by measuring the in vivo H+-pumping activity in
      the same cells. The PM-H+-ATPase activation could not be attributed to
      transcriptional activation of the encoding genes PMA1 and PMA2. CONCLUSIONS: The
      activity of PM-H+-ATPase was stimulated and the internal cell volume decreased
      during yeast adaptation to growth under MCPA stress. Based on the values
      estimated for the pHi, we hypothesize that these cell responses may contribute to
      the restoration of pHi homeostasis during recovery from MCPA stress. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This work is a contribution to the understanding of the
      toxic effects of the herbicide MCPA and of physiological mechanisms underlying
      adaptation to MCPA, in the eukaryotic model S. cerevisiae. Results may be useful
      to elucidate the adaptation mechanisms to this xenobiotic compound in more
      complex and experimentally less-accessible eukaryotes. They also provide
      indications to assist the use of yeast cells as a bioassay system to assess the
      toxicity of phenoxyacetic acid herbicides and of other lipophilic xenobiotics,
      aiming at reducing the use of animals in toxicity testing.

PMID- 14962142
TI  - Monitoring the efficacy of steam and formaldehyde treatment of naturally
      Salmonella-infected layer houses.
AB  - AIMS: To monitor if a temperature-humidity-time treatment found to be effective
      in eliminating Salmonella in laboratory trials (Gradel et al. 2003) was efficient
      against Salmonella in naturally infected layer houses. METHODS AND RESULTS: Six
      layer houses with natural Salmonella infections were steam treated in a download
      period, aiming at >or=60 degrees C and 100% relative humidity (RH) during a 24-h
      period, with or without the addition of 30 ppm formaldehyde. In addition, two
      control layer houses were disinfected chemically. Salmonella samples taken from
      predetermined sites before and after treatment were tested qualitatively for
      Salmonella and coliforms. Samples with indicator bacteria (feed inoculated with
      Escherichia coli or Enterococcus faecalis and faeces with naturally occurring E.
      coli and enterococci) were placed during steam-treatment at 12 sites in each
      house (where the temperature was logged at 5-min intervals) and tested for
      surviving bacteria. Generally, the field test results confirmed the results of
      laboratory tests, especially when 30 ppm formaldehyde was added to the steam. In
      well-sealed houses, the recommended temperature-humidity-time scheme was
      accomplished at a minimum of 10 cm above floor level within 1 h. CONCLUSIONS: A
      steam treatment of >or=60 degrees C and 100% RH during a 24-h period with the
      addition of 30 ppm formaldehyde at the beginning of the process is recommended
      for eliminating Salmonella from naturally infected poultry layer houses.
      SIGNIFICANCE AND IMPACT OF THE STUDY: A specific recommendation for the
      elimination of Salmonella in poultry houses can be given.

PMID- 14962143
TI  - Factorial analysis of tricarboxylic acid cycle intermediates for optimization of
      zeaxanthin production from Flavobacterium multivorum.
AB  - AIMS: To study the effect of intermediates of the tricarboxylic acid (TCA) cycle
      on the production of zeaxanthin from Flavobacterium multivorum in order to
      optimize production of this xanthophyll carotenoid. METHODS AND RESULTS: The
      concentration of selected TCA cycle intermediates (malic acid, isocitric acid and
      alpha-ketoglutarate) was optimized in shake flask culture, using a statistical
      two-level, three-variable factorial approach. The carotenoid production profile
      was also studied in the optimized medium at various growth phases. Optimized
      medium resulted in a sixfold increase in volumetric production of zeaxanthin
      (10.65 +/- 0.63 microg ml-1) using malic acid (6.02 mm), isocitric acid (6.20 mm)
      and alpha-ketoglutarate (0.02 mm). The majority of zeaxanthin was produced in the
      late logarithmic growth phase whereas a substantial amount of beta-cryptoxanthin
      and beta-carotene were observed in the early logarithmic phase. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study demonstrates improvement of zeaxanthin production
      from F. multivorum which might aid in the commercialization of zeaxanthin
      production from this microbe.

PMID- 14962144
TI  - Parvibaculum lavamentivorans converts linear alkylbenzenesulphonate surfactant to
      sulphophenylcarboxylates, alpha,beta-unsaturated sulphophenylcarboxylates and
      sulphophenyldicarboxylates, which are degraded in communities.
AB  - AIMS: The aims were to test whether Parvibaculum lavamentivoransT degraded
      commercial linear alkylbenzenesulphonate (LAS) surfactant via omega-oxygenation
      and beta-oxidation to sulphophenylcarboxylates (SPCs), whether the organism was
      widespread and reisolable, and whether the degradative community used the 4
      sulphocatechol 1,2-dioxygenase to cleave the aromatic ring from LAS. METHODS AND
      RESULTS: Heterotrophic P. lavamentivoransT converted LAS (side chain length C10
      C13) to SPCs (C4-C13), alpha,beta-unsaturated SPCs (C4-C13) and
      sulphophenyldicarboxylates (SPdCs) (at least C8-C12). Identifications came from
      high performance liquid chromatography (HPLC) separation, an electrospray
      interface and mass spectrometry. No evidence for other paths was found. The
      degradation of LAS in trickling filters inoculated with environmental samples
      always showed transient SPC intermediates (HPLC) and the presence of the P.
      lavamentivorans morphotype in the community. One new isolate was obtained. A
      community able to mineralize LAS contained 4-sulphocatechol-1,2-dioxygenase at
      high specific activity. CONCLUSIONS: Parvibaculum lavamentivoransT degrades
      commercial LAS via omega-oxygenation, oxidation and chain shortening through beta
      oxidation to yield a wide range of SPCs. The latter are degraded in bacterial
      communities which contain organisms like P. lavamentivorans, and which utilize
      sulphocatechol dioxygenase for ring cleavage. SIGNIFICANCE AND IMPACT OF THE
      STUDY: There is one widespread pathway to degrade LAS. Any traces of LAS and
      larger amounts of SPCs in the effluent from sewage works are exposed to
      degradative organisms in acclimated and pristine environments. These degradative
      reactions can now be studied in pure cultures.

PMID- 14962145
TI  - The effect of changing practice on fall prevention in a rehabilitative hospital:
      the Hospital Injury Prevention Study.
AB  - OBJECTIVES: To determine whether a change in practice to introduce a
      multidisciplinary fall-prevention program can reduce falls and injury in nonacute
      patients in a rehabilitation hospital. DESIGN: A quasi-experimental study.
      SETTING: Three geriatric wards with a similar design, equipment, staffing levels,
      and skill mix. PARTICIPANTS: Eight hundred twenty-five consecutive patients.
      INTERVENTION: The patients' fall-risk status was assessed using the Downton
      Score. Current practice was maintained on the two control wards (n=550). On the
      experimental ward (n=275), a fall-prevention program was introduced. A
      multidisciplinary team met weekly specifically to discuss patients' fall risk and
      formulate a targeted plan. Patients at risk were identified using wristbands;
      risk factors were corrected or environmental changes made to enhance safety.
      MEASUREMENTS: Primary outcomes were number of fallers, recurrent fallers, total
      falls, patients sustaining injury, and falls per occupied bed days. Secondary
      outcomes were place of discharge and mortality. RESULTS: Patients were matched
      for age and risk status. Control wards had proportionally more fallers (20.2% vs
      14.2%: P=.033), patients sustaining injury (8.2% vs 4%: P=.025), and total number
      of falls (170 vs 72: P=.045). These results did not remain significant after
      controlling for differing length of stay. There was no reduction in recurrent
      fallers (6.4% vs 4.7%: P=.43) and no effect on place of discharge (home
      discharges; 57.5% vs 60.7%: P=.41) or mortality (15.3% vs 13.8%: P=.60).
      CONCLUSION: This study shows that falls might be reduced in a multidisciplinary
      fall-prevention program, but the results are not definitive because of the
      borderline significance achieved and the variable length of stay. More research
      on fall prevention in hospital is required, particularly as to what
      interventions, if any, are effective at reducing falls in this group of patients.

PMID- 14962146
TI  - Predictors of adherence to the use of hip protectors in nursing home residents.
AB  - OBJECTIVES: To assess predictors of hip-protector use in nursing home residents
      under usual-care conditions and after intervention consisting of structured
      education of nurses and nursing home residents and provision of free hip
      protectors. DESIGN: Nested cohort analyses within a cluster randomized,
      controlled trial with 18 months follow-up. SETTING: Forty-nine nursing home
      clusters in Hamburg, Germany. PARTICIPANTS: Residents with at least one fall
      during the study period (intervention group, n=237; usual-care group, n=274).
      MEASUREMENTS: Use of hip protector while falling. Regression analyses were
      performed for each of the two cohorts of fallers using the time to the first fall
      without hip protector as the dependent variable. Predefined nursing home cluster
      related parameters (center, staffing ratio, proportion of registered nurses in
      nursing staff, hip-protector use before study period) and resident-related
      parameters (sex, history of falls and fractures, fear of falling, urinary
      incontinence, use of walking aid, degree of disablement) were considered as
      explanatory variables. RESULTS: Under usual care, 97% of fallers (n=266),
      compared with 62% (n=148) in the intervention group, experienced at least one
      fall without hip protection. Using Cox proportional hazards models with and
      without frailty parameter (random cluster effect), the following predictors were
      identified: intervention group: use of walking aid, hazard ratio (HR)=1.53 (95%
      confidence interval (CI):0.98-2.39) and no urinary incontinence, HR=1.47 (95%
      CI:1.03-2.09); usual care: nursing staff per 10 residents, HR=0.78 (95% CI=0.63
      0.96); high degree of disablement, HR=1.38 (95% CI=1.06-1.80); strong fear of
      falling, HR=0.78 (95% CI=0.60-1.02). The nursing home cluster was a significant
      predictor in the control group (P=.029), but not in the intervention group
      (P=.100). CONCLUSION: Only a few and weak predictors of hip-protector use of
      questionable relevance could be identified in both groups. Future research should
      concentrate on the implementation of interventions of proven efficacy, such as
      provision of hip protectors combined with structured education of staff and
      residents.

PMID- 14962147
TI  - Declining executive control in normal aging predicts change in functional status:
      the Freedom House Study.
AB  - OBJECTIVES: To assess the contribution of executive control function (ECF) to
      functional status. DESIGN: Three-year longitudinal cohort study. SETTING: A
      comprehensive-care retirement community. PARTICIPANTS: Five hundred forty-seven
      noninstitutionalized septuagenarians. MEASUREMENTS: The Mini-Mental State
      Examination (MMSE) and Executive Interview (EXIT25). Functional status was
      assessed using instrumental activities of daily living (IADLs). Latent growth
      curves of MMSE, EXIT25, and IADL were modeled. The rate of change in IADLs
      (DeltaIADL), adjusted for baseline IADLs and cognition, was regressed on the rate
      of change in each cognitive measure (adjusted for baseline cognition). Models
      were also adjusted for baseline age, level of care, and comorbid illnesses.
      RESULTS: Baseline test scores were within normal ranges, but mean EXIT25 scores
      reached the impaired range by the second follow-up. There was significant
      variability around the baseline means and slopes for all variables. The rate of
      change in EXIT25 was strongly correlated with DeltaIADL (r=-0.57, P<.001). This
      remained significant after adjusting for baseline EXIT25 scores, IADLs, age,
      comorbid disease, and level of care. The effect of the EXIT25 on DeltaIADL was
      stronger than those of age, baseline IADLs, comorbid disease, or level of care.
      The rate of change in MMSE scores was not significantly associated with
      DeltaIADL. CONCLUSION: ECF is a significant and independent correlate of
      functional status in normal aging. Traditional dementia case finding is likely to
      underestimate cognition-related disability. Neither a normal baseline MMSE score
      nor stable MMSE scores over time preclude functionally significant changes in
      ECF.

PMID- 14962148
TI  - Effect of widowhood on disability onset in elderly men from three European
      countries.
AB  - OBJECTIVES: To investigate in different countries the effects of becoming
      widowed, duration of widowhood, and household composition of widowed men on
      disability onset in different disability domains. DESIGN: Longitudinal data from
      a cohort study collected around 1990, 1995, and 2000. SETTING: Three cohorts from
      Finland, The Netherlands, and Italy. PARTICIPANTS: Seven hundred thirty-six men,
      aged 70 and older at baseline. MEASUREMENTS: Disability was measured using
      standardized questionnaire on activities of daily living (ADLs). Three domains
      were assessed: instrumental ADLs (IADLs), mobility, and basic ADLs (BADLs).
      Duration of widowhood was divided into less than 5 years and 5 or more years and
      household composition into living alone and living with family or in an
      institution. RESULTS: Men who became widowed developed more IADL disabilities
      (odds ratio (OR)=2.15; 95% confidence interval (CI)=1.22-3.81) and mobility
      (OR=1.84; 95% CI=1.15-2.96) than men who were still married. Men who had been
      widowed for less than 5 years developed more IADL disabilities than those who had
      been widowed for 5 years or more (OR=2.27; 95% CI=1.14-4.54). Widowed men living
      alone showed fewer disabilities in mobility (OR=0.25; 95% CI=0.09-0.73) and BADLs
      (OR=0.02; 95% CI=0.001-0.33) than those living with others. The effects on
      disability onset did not differ between countries. CONCLUSION: Widowhood in
      elderly men is a risk factor for dependency in IADLs and mobility. The growth in
      the number of widowers may lead to higher demands on family care and professional
      care.

PMID- 14962149
TI  - The National Pressure Ulcer Long-Term Care Study: pressure ulcer development in
      long-term care residents.
AB  - OBJECTIVES: To identify resident, treatment, and facility characteristics
      associated with pressure ulcer (PU) development in long-term care residents.
      DESIGN: Retrospective cohort study with convenience sampling. SETTING: Ninety
      five long-term care facilities participating in the National Pressure Ulcer Long
      Term Care Study throughout the United States. PARTICIPANTS: A total of 1,524
      residents aged 18 and older, with length of stay of 14 days or longer, who did
      not have an existing PU but were at risk of developing a PU, as defined by a
      Braden Scale for Predicting Pressure Sore Risk score of 17 or less, on study
      entry. MEASUREMENTS: Data collected for each resident over a 12-week period
      included resident characteristics (e.g., demographics, medical history, severity
      of illness using the Comprehensive Severity Index, Braden Scale scores,
      nutritional factors), treatment characteristics (nutritional interventions,
      pressure management strategies, incontinence treatments, medications), staffing
      ratios and other facility characteristics, and outcome (PU development during
      study period). Data were obtained from medical records, Minimum Data Set, and
      other written records (e.g., physician orders, medication logs). RESULTS: Seventy
      one percent of subjects (n=1,081) did not develop a PU during the 12-week study
      period; the remaining 29% of residents (n=443) developed a new PU. Resident,
      treatment, and facility characteristics associated with greater likelihood of
      developing a Stage I to IV PU included higher initial severity of illness,
      history of recent PU, significant weight loss, oral eating problems, use of
      catheters, and use of positioning devices. Characteristics associated with
      decreased likelihood of developing a Stage I to IV PU included new resident,
      nutritional intervention (e.g., use of oral medical nutritional supplements and
      tube feeding for >21 days), antidepressant use, use of disposable briefs for more
      than 14 days, registered nurse hours of 0.25 hours per resident per day or more,
      nurses' aide hours of 2 hours per resident per day or more, and licensed
      practical nurse turnover rate of less than 25%. When Stage I PUs were excluded
      from the analyses, the same variables were significant, with the addition of
      fluid orders associated with decreased likelihood of developing a PU. CONCLUSION:
      A broad range of factors, including nutritional interventions, fluid orders,
      medications, and staffing patterns, are associated with prevention of PUs in long
      term care residents. Research-based PU prevention protocols need to be developed
      that include these factors and target interventions for reducing risk factors.

PMID- 14962150
TI  - Large-artery stiffness contributes to the greater prevalence of systolic
      hypertension in elderly women.
AB  - OBJECTIVES: To determine whether sex differences in large-artery stiffness
      contribute to the greater prevalence of systolic hypertension in elderly women
      than in elderly men. DESIGN: During a single visit arterial stiffness was
      assessed in the unmedicated state using four parameters. PARTICIPANTS: Three
      hundred seventy-four women with a mean age+/-standard deviation of 72+/-5 and 296
      men aged 71+/-5 participated. SETTING: Hypertensive patients were recruited from
      general practice as part of the second Australian National Blood Pressure Study
      in Melbourne, Australia. MEASUREMENTS: Large-artery stiffness was assessed using
      multiple methodologies, including aortic arch stiffness (beta-index) using M-mode
      ultrasound and arterial compliance and augmentation index using noninvasive
      carotid pressure and aortic flow measurements. RESULTS: Women had greater carotid
      and brachial pulse pressure (PP) than men (P<.001), despite higher mean arterial
      pressure in men. Mean arterial compliance was lower in women (0.20+/-0.12 vs
      0.28+/-0.16 mL/mmHg, P<.001) even after correction for aortic area, and aortic
      arch stiffness was higher (30+/-36 vs 23+/-22; P<.01). Consistent with both a
      stiffer proximal circulation and a shorter distance to reflection sites, women
      had higher augmentation index (38+/-11% vs 29+/-12%, P<.001). In multivariate
      analysis, sex was an independent determinant of all arterial stiffness indices.
      CONCLUSION: Independently of known confounders, elderly hypertensive women have
      stiffer large arteries, greater central wave reflection, and higher PP than
      elderly men. Stiffer large arteries likely contribute to the greater prevalence
      of systolic hypertension in elderly women and may partly explain the acceleration
      in postmenopausal cerebrovascular and cardiac complications.

PMID- 14962151
TI  - Tramadol/acetaminophen combination tablets for the treatment of pain associated
      with osteoarthritis flare in an elderly patient population.
AB  - OBJECTIVES: To evaluate the efficacy and safety of adding tramadol 37.5
      mg/acetaminophen (APAP) 325 mg combination tablets (tramadol/APAP) to existing
      therapy for painful osteoarthritis (OA) flare in a subset of elderly patients.
      DESIGN: Randomized, double-blind, placebo-controlled, 10-day add-on study.
      SETTING: Thirty outpatient centers. PARTICIPANTS: Of 308 patients with painful OA
      flare, a subset of 113 patients aged 65 and older. MEASUREMENTS: Average daily
      pain intensity and pain relief scores for Days 1 through 5 and secondary quality
      of-life measures and medication assessments. METHODS: Patients received one or
      two tramadol/APAP tablets or placebo four times per day for 10 days during
      ongoing nonselective or cyclooxygenase (COX)-2-selective nonsteroidal
      antiinflammatory drug (NSAID) therapy. RESULTS: Tramadol/APAP (n=69) was
      significantly superior to placebo (n=44) for average daily pain intensity
      (P=.034) and pain relief (P=.010) for Days 1 through 5 and Days 1 through 10
      (P=.012 and P=.019, respectively). Tramadol/APAP had significantly better
      investigator (P<.001) and patient (P=.001) overall medication assessments and
      significantly better scores on three of four Western Ontario and McMaster
      Universities Osteoarthritis Index measures (P< or =.027). Most common adverse
      events with tramadol/APAP were nausea (18.8%), vomiting (13.0%), dizziness
      (11.6%), and constipation (4.3%), with an incidence similar to that of the
      overall study population. Mean daily dose of tramadol/APAP was 4.5 tablets (168
      mg/1,458 mg). CONCLUSION: Tramadol/APAP add-on therapy effectively managed
      painful OA flare in this elderly subset and was generally well tolerated.

PMID- 14962152
TI  - A randomized, controlled trial of doxycycline and rifampin for patients with
      Alzheimer's disease.
AB  - OBJECTIVES: To assess whether doxycycline and rifampin have a therapeutic role in
      patients with Alzheimer's disease (AD). DESIGN: Randomized, triple-blind,
      controlled trial. SETTING: Three tertiary care and two community geriatric
      clinics in Canada. PARTICIPANTS: One hundred one patients with probable AD and
      mild to moderate dementia. INTERVENTION: Oral daily doses of doxycycline 200 mg
      and rifampin 300 mg for 3 months. MEASUREMENTS: The primary outcome was a change
      in Standardized Alzheimer's Disease Assessment Scale cognitive subscale
      (SADAScog) at 6 months. Secondary outcomes were changes in the SADAScog at 12
      months and tests of dysfunctional behavior, depression, and functional status.
      RESULTS: There was significantly less decline in the SADAScog score at 6 months
      in the antibiotic group than in the placebo group, (-2.75 points, 95% confidence
      interval (CI)=-5.28 to -0.22, P=.034). At 12 months, the difference between
      groups in the SADAScog was -4.31 points (95% CI=-9.17-0.56, P=.079). The
      antibiotic group showed significantly less dysfunctional behavior at 3 months.
      There was no significant difference in adverse events between groups (P=.34).
      There were no differences in Chlamydia pneumoniae detection using polymerase
      chain reaction or antibodies (immunoglobulin (Ig)G or IgA) between groups.
      CONCLUSION: Therapy with doxycycline and rifampin may have a therapeutic role in
      patients with mild to moderate AD. The mechanism is unlikely to be due to their
      effect on C. pneumoniae. More research is needed to investigate these agents.

PMID- 14962153
TI  - Aging does not affect beta-agonist responsiveness after methacholine-induced
      bronchoconstriction.
AB  - OBJECTIVES: To assess the response to an inhaled beta-agonist alone or in
      combination with an anticholinergic agent after methacholine-induced
      bronchoconstriction in four age groups. DESIGN: Retrospective analysis. SETTING:
      Pulmonary function laboratory in a university-affiliated hospital. PARTICIPANTS:
      Seven hundred sixty-four consecutive subjects with a 20% reduction or more in
      forced expiratory volume during the first second (FEV1) of exhalation from total
      lung capacity after inhaling 189 or fewer cumulative units of methacholine were
      included in the analysis. INTERVENTION: The first 382 subjects received three
      inhalations of metaproterenol (total of 1.95 mg), and the other 382 subjects
      received three inhalations of albuterol and ipratropium combination (total of 309
      microg of albuterol and 54 microg of ipratropium) after methacholine-induced
      bronchoconstriction. MEASUREMENTS: The response to bronchodilators was assessed
      as the postbronchodilator percentage change in FEV1 and the percentage of
      subjects recovering to 90% or better of baseline FEV1 after the use of
      bronchodilator. RESULTS: The percentage change in FEV1 postbronchodilator in the
      elderly was similar to that of the younger subjects. The percentage of subjects
      who recovered to 90% or better of their baseline FEV1 postbronchodilator was also
      similar in the elderly and younger age groups. Response to metaproterenol was
      similar to that of the albuterol/ipratropium combination in all age groups (all
      P>.05). CONCLUSION: Aging does not affect bronchodilator response to beta-agonist
      after methacholine-induced bronchoconstriction. The responsiveness to beta
      agonist alone is similar to the responsiveness to the combination of beta-agonist
      and anticholinergic agent in all age groups.

PMID- 14962154
TI  - Effect of state Medicaid reimbursement rates on hospitalizations from nursing
      homes.
AB  - OBJECTIVES: To estimate the effect of state Medicaid nursing home reimbursement
      rates on hospitalizations of nursing home residents. DESIGN: Cross-sectional
      sample of nongovernment-owned nursing homes with 25 beds or more in one
      Metropolitan Statistical Area in each of 10 states in 1993, with 6 months follow
      up on mortality and hospitalizations. SETTING: Two hundred fifty-three nursing
      homes. PARTICIPANTS: Eight to 16 randomly selected residents from each facility,
      totaling 2,080. MEASUREMENTS: Minimum Data Set assessments conducted by research
      nurses at baseline. A three-category 6-month outcome was defined as (1) any
      hospitalization; for those not hospitalized, (2) death versus (3) alive in the
      facility. RESULTS: Using multinomial logistic regression, adjusted to survey
      design, controlling for resident and facility characteristics, a 10 dollar
      increase in 1993 Medicaid reimbursement rate above the mean rate of approximately
      75 dollars resulted in a 9% reduction in a resident's risk of hospitalization
      (P<.05). CONCLUSION: State Medicaid reimbursement rates appear to affect clinical
      decisions regarding the need for hospital admission and thresholds for nursing
      home use. The findings from this study reemphasize the importance of properly
      aligning state Medicaid and federal Medicare long-term care policies because,
      currently, states have no incentive to increase reimbursement rates to avoid
      hospitalization.

PMID- 14962155
TI  - Diverse effect of inflammatory markers on insulin resistance and insulin
      resistance syndrome in the elderly.
AB  - OBJECTIVES: To evaluate the potential association between different inflammatory
      markers and insulin resistance (IR), as well as insulin-resistance syndrome (IRS)
      in a large, population-based study of older, nondiabetic persons. DESIGN: Cross
      sectional study. SETTING: Outpatient clinic in Greve in Chianti and Bagno a
      Ripoli (Italy). PARTICIPANTS: One thousand one hundred forty-six nondiabetic
      subjects ranging in age from 22 to 104. MEASUREMENTS: Anthropometric
      measurements; plasma fasting levels of glucose, insulin, and cholesterol (total,
      high-density lipoprotein, low-density lipoprotein); homeostasis model assessment
      to estimate degree of insulin resistance; tumor necrosis factor alpha (TNF
      alpha), interleukin 6 (IL-6), soluble IL-6 receptor (sIL-6R), interleukin
      receptor antagonist (IL-1ra), and C-reactive protein (CRP) plasma concentrations;
      diastolic, systolic, and mean arterial blood pressure; and echo-color-Doppler
      duplex scanning examination of carotid arteries. RESULTS: Insulin resistance
      correlated with age (r=0.102; P<.001) and plasma levels of TNF-alpha (r=0.082;
      P=.007), IL-1ra (r=0.147; P<.001), IL-6 (r=0.133; P<.001), sIL-6R (r=-0.156;
      P<.001), and CRP (r=0.83; P<.001). Subjects in the upper tertile of IR degree
      were older and had higher serum levels of TNF-alpha, IL-1ra, and IL-6 and lower
      levels of sIL-6R than subjects in the lowest tertile. Independent of age, sex,
      body mass index, waist-to-hip ratio, triglycerides, drug intake, diastolic blood
      pressure, smoking habit, and carotid atherosclerotic plaques, higher IL-6
      (t=2.987; P=.003) serum concentrations were associated with higher IR, whereas
      sIL-6R levels (t=-5.651; P<.001) were associated with lower IR. Furthermore, IL
      1ra concentrations (t=2.448; P=.015) were associated with IRS, and higher sIL-6R
      plasma levels continued to correlate negatively with IRS. CONCLUSION: Different
      inflammatory markers are associated with a diverse effect on IR and IRS in
      elderly nondiabetic subjects.

PMID- 14962156
TI  - Impairments of muscles and nerves associated with peripheral arterial disease and
      their relationship with lower extremity functioning: the InCHIANTI Study.
AB  - OBJECTIVES: To define the relationships between lower extremity peripheral
      arterial disease (PAD), pathophysiological findings in lower extremity muscles
      and nerves, and lower extremity performance. DESIGN: Cross-sectional. SETTING:
      Two communities in Italy. PARTICIPANTS: Nine-hundred seventy-nine community
      dwelling men and women aged 60 and older (109 with PAD). MEASUREMENTS: Presence
      and degree of lower extremity arterial obstruction were determined using the
      ankle-brachial index (ABI). Lower extremity muscle cross-sectional area was
      measured using computed tomography. Peroneal nerve conduction velocity (NCV) and
      leg power were also determined. Measures of lower extremity functioning were fast
      walking speed over 4 meters, time required to walk 400 meters, and the summary
      performance score. RESULTS: Participants with PAD had significantly poorer
      performance on functional outcomes than participants without PAD. Adjusting for
      age and sex, presence of PAD was associated with reduced leg muscle power (83.69
      vs 103.51 watts, P<.001), reduced muscle cross-sectional area (61.5 vs 63.5 cm2,
      P=.14), and reduced NCV (43.0 vs 44.2 m/s, P=.003). Adjustment for leg power
      diminished the independent association between ABI and the functional outcomes
      measures. CONCLUSION: In community-dwelling individuals, PAD is associated with
      reduced NCV and reduced muscle power in the lower extremities. Muscle power may
      mediate the association between lower ABI levels and poorer functional
      performance.

PMID- 14962157
TI  - Brisk walking speed in older adults who walk for exercise.
AB  - OBJECTIVES: To determine the self-selected exercise intensity of older adults who
      report that they walk briskly for exercise. An additional aim of the study was to
      assess the contribution of self-reported physical activity to self-selected
      exercise intensity. DESIGN: Observational. SETTING: walking path. PARTICIPANTS:
      Subjects consisted of 212 participants in the Study of Physical Performance and
      Age-Related Changes in Sonomans who stated in a detailed home interview that they
      walked briskly for exercise. MEASUREMENTS: Observed brisk walking speed was
      measured as the time it took participants to walk half a mile at "normal brisk
      walking speed." Self-reported physical activity was categorized as metabolic
      equivalent of the task (MET) in minutes of exercise reported in the previous 7
      days. Physiological measures and body composition were obtained through
      laboratory evaluation. RESULTS: Men walked at an average speed+/-standard
      deviation of 5.72+/-0.69 km/h and women walked at an average speed of 5.54+/-0.64
      km/h. Self-reported physical activity was not associated with brisk walking speed
      when adjusted for age and ratio of lean to fat mass. CONCLUSION: This study found
      that older adults who report that they walk briskly for exercise do so at a pace
      considered moderate or greater in absolute intensity as indicated by their
      walking speed (4.83 km/h). Ninety-eight percent of men (93/95) and 97% of women
      (113/117) had an observed walking speed equivalent to 3 or more METs based on
      their calculated walking speed.

PMID- 14962158
TI  - Potentially inappropriate antiepileptic drugs for elderly patients with epilepsy.
AB  - OBJECTIVES: To describe prescribing patterns for older veterans with epilepsy,
      determine whether disparity exists between these patterns and clinical
      recommendations, and describe those at greatest risk of receiving potentially
      inappropriate antiepileptic drugs (AEDs). DESIGN: Retrospective administrative
      database analysis. SETTING: All outpatient facilities within the Department of
      Veterans Affairs (VA). PARTICIPANTS: All veterans aged 65 and older who had
      epilepsy diagnosed before the end of fiscal year 1999 (FY99) and who received
      AEDs from the VA in FY99 (N=21,435). MEASUREMENTS: National VA pharmacy data were
      used to determine the AED regimen based on the AEDs patients received during the
      year. Administrative data were used to describe demographic variables and to
      gauge disease severity and epilepsy onset. RESULTS: Approximately 17% of patients
      received phenobarbital and 54% phenytoin. Patients classified as having newly
      diagnosed disease were less likely to receive phenobarbital monotherapy and
      combination therapy and more likely to receive gabapentin or lamotrigine
      monotherapy (chi2=288.90, P<.001). Logistic regression analyses indicated that,
      for all patients, those with more severe disease were less likely to receive
      phenobarbital monotherapy than other monotherapy and phenobarbital combinations
      than other combinations. Those who received specialty consultation were less
      likely to receive phenytoin monotherapy than AED monotherapy, which is consistent
      with clinical recommendations. CONCLUSION: Most older veterans received
      potentially inappropriate AED therapy. Hence, the standard of care for older
      patients with epilepsy should be reevaluated, although the vast use of phenytoin
      in this population suggests that change in practice patterns may be difficult.

PMID- 14962159
TI  - Mechanisms of unexplained anemia in the nursing home.
AB  - OBJECTIVES: To characterize anemia in elderly nursing home residents. DESIGN:
      Prospective multiinstitutional cohort study. SETTING: Five nursing homes.
      PARTICIPANTS: From retrospective analysis, residents found to be anemic using
      chart review were prospectively randomized. Of the 81 residents enrolled, 60 were
      anemic. MEASUREMENTS: Chart review for medical history and factors related to
      treatment or history of anemia, extensive laboratory evaluation for causes of
      anemia, and classification of anemia by two hematologists. RESULTS: Among the 60
      anemic residents, the causes of anemia were idiopathic (n=27), iron-deficiency
      (n=14), anemia associated with chronic disease (n=8), anemia of renal
      insufficiency (n=6), and other (n=5). The eryrthropoietin (EPO) response to
      anemia was lower in residents with idiopathic anemia (IA) than in those with iron
      deficiency anemia, and this correlated with renal function as estimated using
      calculated creatinine clearance. In this elderly population, advancing age was
      not correlated with lower EPO response. CONCLUSION: IA is common in nursing home
      residents. A lower EPO response contributes to the high prevalence of anemia in
      this setting and may be due, in part, to occult renal dysfunction.

PMID- 14962160
TI  - Stroke prophylaxis in institutionalized elderly patients with atrial
      fibrillation.
AB  - OBJECTIVES: To identify patterns and predictors of antithrombotic use and to
      evaluate the appropriateness of antithrombotic therapy for stroke prophylaxis in
      institutionalized elderly patients with atrial fibrillation. DESIGN:
      Retrospective study. SETTING: Seventeen long-term care institutions in Edmonton,
      Alberta. SUBJECTS: Two hundred sixty-five long-term care residents, aged 65 and
      older, with atrial fibrillation. MEASUREMENTS: The proportion of patients who
      were prescribed warfarin, acetylsalicylic acid (ASA), both, or neither was
      determined. Odds ratios were calculated to identify risk factors for stroke and
      bleeding that are predictive of the receipt of anticoagulant therapy.
      Appropriateness of therapy was evaluated based on whether patients were
      prescribed antithrombotic therapy in accordance with their risk factors for
      stroke and bleeding. RESULTS: Warfarin was prescribed for 49% of patients, ASA
      for 22%, both for 8%, and neither for 20%. Nearly all patients (97%) were
      considered to be at high risk for stroke, with age being the predominant risk
      factor (88%>75), whereas about half were considered to be at low risk for
      bleeding. Multivariate analyses did not find any associations between individual
      risk factors for bleeding and anticoagulant treatment, with the exception of
      recent surgery (odds ratio=0.59, 95% confidence interval=0.37-0.94). Overall,
      54.8% of patients received appropriate antithrombotic therapy. Of patients who
      were optimal candidates for anticoagulation, 60% received appropriate therapy
      (warfarin with or without ASA). CONCLUSION: Although warfarin was the most
      appropriate treatment in nearly all of this population at high risk for stroke,
      it was prescribed in fewer than two-thirds of patients. Antithrombotic therapy
      was not always prescribed in accordance with patients' risk factors for stroke
      and bleeding. There is a need for systematic identification of appropriate
      candidates for anticoagulation in the long-term care setting.

PMID- 14962161
TI  - Predictors of nursing facility admission: a 12-year epidemiological study in the
      United States.
AB  - OBJECTIVES: To identify predictors of institutionalization in a community-based
      cohort of older adults. DESIGN: Prospective, longitudinal. After initial
      assessment at study entry, surviving participants were reassessed in a series of
      approximately biennial waves until October 2001; baseline for the current
      analysis was Wave 2 (1989-91). SETTING: Largely rural, blue-collar community in
      the mid-Monongahela Valley of southwestern Pennsylvania. PARTICIPANTS: A
      population-based cohort of 1,147 adults, aged 66 and older (mean 74.1) at
      baseline, who were not already institutionalized and who had complete data on all
      variables of interest. MEASUREMENTS: Cox proportional hazards models were used to
      identify predictors of institutionalization from among selected variables
      measured at baseline, including age, sex, education, marital status, living
      arrangements, ability to perform instrumental activities of daily living (IADLs),
      depressive symptoms, number of prescription medications (as an index of overall
      morbidity), self-reported social support, hospitalization during the preceding
      year, and cognitive functioning. Dementia was defined according to the
      operational criteria of the Diagnostic and Statistical Manual of Mental
      Disorders, Third Edition, Revised, and by a Clinical Dementia Rating of 0.5 or
      greater, based on a standardized clinical assessment. The outcome variable was
      institutionalization, defined as entry into in a nursing home. RESULTS:
      Significant predictors of institutionalization were dementia (hazard ratio
      (HR)=5.09, 95% confidence interval (CI)=2.92-8.84), measured as a time-dependent
      variable; older age (HR=1.06, 95% CI=1.03-1.10); IADL disability (HR=1.31, 95%
      CI=1.15-1.50); worse/less social support (HR=1.27, 95% CI=1.10-1.46); and number
      of prescription medications (HR=1.21, 95% CI=1.11-1.32), measured at baseline.
      The interaction between number of prescription drugs and dementia was also
      significant, suggesting that prescription medication count had less effect on
      institutionalization in those with dementia than in those without. CONCLUSION:
      Dementia emerged as the most potent risk factor for institutionalization in this
      12-year community-based epidemiological study. Medical burden conferred greater
      vulnerability to institutionalization in nondemented persons than in those with
      dementia.

PMID- 14962162
TI  - Screening and cognitive impairment: ethics of forgoing mammography in older
      women.
AB  - Mammographic screening for breast cancer in cognitively impaired women poses
      significant ethical questions. Many woman with dementia should not be screened
      because of the greater harm than benefits and the difficulty in obtaining
      informed consent. This article reviews the current controversy about mammography
      and then suggests a risk/benefit analysis for this vulnerable population.
      Autonomy, decision-making capacity, and the roles of surrogates and physicians
      are considered, as are ageism and the risk of undertreatment. The harm of
      overdiagnosis and subsequent overtreatment for women who are cognitively
      impaired, have comorbidity and a limited life span are outlined. In these cases,
      the burdens of mammography outweigh the benefits. For women with early cognitive
      impairment and longer life expectancies, the potential benefits may outweigh the
      harms. A decision-making process by the patient, proxy, and practitioner that
      takes account of foreseeable risks and benefits, patient capacity and
      preferences, and the effect of this screening intervention on quality of life is
      outlined.

PMID- 14962163
TI  - Predictors of nursing home placement in African Americans with dementia.
AB  - The objective of the present study was to identify predictors of
      institutionalization in African Americans who suffer from dementia. Data were
      derived from the Medicare Alzheimer's Disease Demonstration Evaluation (MADDE),
      which collected information on Alzheimer's patients and their family caregivers
      over a 3-year period. The baseline MADDE sample included 667 older African
      Americans suffering from dementia recruited from eight catchment areas in the
      United States. A Cox proportional hazards model was used to create a predictive
      model of institutionalization. Subsequent analyses found that care recipient age,
      sex, Medicaid eligibility, and cognitive impairment; site; and caregiving burden
      were significant predictors of time to placement. The results, among the first to
      examine predictors of nursing home placement of cognitively impaired African
      Americans, emphasize the clinical implications and complex interplay of race,
      dementia, and caregiving context in the institutionalization process.

PMID- 14962164
TI  - Research agenda-setting program for geriatric ophthalmology.
AB  - The healthcare needs of an aging population of "baby boomers" (persons born
      between 1946 and 1964) will disproportionately affect ophthalmology. To meet this
      emerging need, the American Geriatrics Society and the John A. Hartford
      Foundation developed a research agenda-setting process for geriatric
      ophthalmology. A systematic literature search was performed using Medline from
      the years 1990 to 2000. The literature review (168 papers) was performed to
      determine the current state of information regarding selected issues in geriatric
      ophthalmology. A needs assessment for each of the identified topics was
      performed, gaps in the existing knowledge base were identified, and key questions
      for future research were proposed. A research agenda-setting process for
      geriatric ophthalmology might provide a structural framework for future research
      efforts in the field.

PMID- 14962166
TI  - Building the science of falls-prevention research.

PMID- 14962167
TI  - The "subsyndromal" syndromes of aging.

PMID- 14962168
TI  - Prevention of gastroesophageal reflux using an application of half-solid
      nutrients in patients with percutaneous endoscopic gastrostomy feeding.

PMID- 14962169
TI  - The role of positron emission tomography in the diagnosis of Alzheimer's disease.

PMID- 14962171
TI  - Cholesterol and mortality in elderly patients.

PMID- 14962172
TI  - Loxoprofen sodium and survival in older people with advanced non-small cell lung
      cancer.

PMID- 14962174
TI  - A case report of corticobasal degeneration.

PMID- 14962175
TI  - Adherence to vitamin D supplementation in elderly patients after hip fracture.

PMID- 14962176
TI  - The use of an electromechanical device for treatment of constipation in the
      elderly.

PMID- 14962177
TI  - Nonconvulsive status epilepticus in the elderly.

PMID- 14962178
TI  - Nursing homes' use of feeding tubes.

PMID- 14962179
TI  - Enoxaparin-associated spontaneous retroperitoneal hematoma in elderly patients
      with impaired creatinine clearance: a report of two cases.

PMID- 14962182
TI  - B-cell positive selection and peripheral homeostasis.

PMID- 14962183
TI  - The avian B-cell receptor complex: distinct roles of Igalpha and Igbeta in B-cell
      development.
AB  - The bursa of Fabricius has evolved in birds as a gut-associated site of B-cell
      lymphopoiesis that is segregated from the development of other hematopoietic
      lineages. Despite differences in the developmental progression of chicken as
      compared to murine B-cell lymphopoiesis, cell-surface immunoglobulin (sIg)
      expression has been conserved in birds as an essential checkpoint in B-cell
      development. B-cell precursors that express an sIg complex that includes the
      evolutionarily conserved Igalpha/beta heterodimer colonize lymphoid follicles in
      the bursa, whereas B-cell precursors that fail to express sIg due to non
      productive V(D)J recombination are eliminated. Productive retroviral gene
      transfer has allowed us to introduce chimeric receptor constructs into developing
      B-cell precursors in vivo. Chimeric proteins comprising the extracellular and
      transmembrane regions of murine CD8alpha fused to the cytoplasmic domain of
      chicken Igalpha efficiently supported B-cell development in precursors that
      lacked endogenous sIg expression. By contrast, expression of an equivalent
      chimeric receptor containing the cytoplasmic domain of Igbeta actively inhibited
      B-cell development. Consequently, the cytoplasmic domains of Igalpha and Igbeta
      play functionally distinct roles in chicken B-cell development.

PMID- 14962184
TI  - Basal B-cell receptor signaling in B lymphocytes: mechanisms of regulation and
      role in positive selection, differentiation, and peripheral survival.
AB  - B-cell development is a highly ordered multistep process dependent upon signals
      generated by the pre-B and B-cell antigen receptor (BCR). BCR signals drive
      maturation of the B cell by integrating a number of parallel and sequential
      biological processes that result in generation of fully immunocompetent B cells.
      Among these biological processes are positive selection through several
      developmental checkpoints, negative selection of potentially self-reactive B
      cells, and activation of the mature B cell. In addition, recent studies have
      shown that developing and mature B cells rely on the constant activity of the BCR
      for their continued survival. Ligand (antigen)-dependent and -independent
      mechanisms of BCR signaling have been proposed, but their specific contributions
      to B-cell maturation and differentiation in the bone marrow and periphery are not
      completely clear. We discuss here a model, whereby ligand-independent basal BCR
      activity would be sufficient to trigger B-cell development through to the mature
      stage. However, long-term survival and formation of specific mature B-cell
      populations may be dependent on ligand-receptor interactions.

PMID- 14962185
TI  - Molecular mechanisms guiding late stages of B-cell development.
AB  - In mice, large numbers of immature B cells are continuously produced in the bone
      marrow. To enter the pools of mature B cells, these immature B cells have to pass
      two checkpoints. First, B cells have to migrate from the bone marrow to the
      spleen. The second checkpoint involves the immature B cells differentiating to
      mature B cells within the spleen. As the net result of this selection and
      maturation, only a fraction of the newly produced B cells enters the mature B
      cell pool. Recent advances in the understanding of the molecular mechanisms that
      operate at these two checkpoints are described and discussed.

PMID- 14962186
TI  - Positive selection focuses the VH12 B-cell repertoire towards a single B1
      specificity with survival function.
AB  - B cells of varying antigen specificities are consistently present in the
      unmanipulated repertoire. These B cells appear to belong to the marginal zone
      (MZ) and B1 B-cell subsets and provide protection to the blood and lymph,
      respectively. Some are specific for self-antigens, suggesting that they are
      selected based on specificity for self but have a protective role against foreign
      pathogens. One of these specificities is for phosphatidylcholine (PtC). Anti-PtC
      B cells comprise 5-8% of the B1 repertoire and are protective against bacterial
      pathogens. In general, they are restricted to the expression of two VH/Vkappa
      combinations, VH11/Vkappa9 and VH12/Vkappa4/5H. This review focuses on the
      differentiation of VH12 anti-PtC B cells. They undergo a series of positive
      selection events beginning at the pre-B-cell stage that enriches for those with a
      VHCDR3 and L chain required for PtC binding and eliminating the majority of VH12
      B cells that lack the ability to bind PtC. Thus, positive selection focuses the
      VH12 repertoire toward PtC, ensuring that anti-PtC VH12 B cells are a significant
      component of the B1-cell repertoire in all individuals.

PMID- 14962187
TI  - Selection during development of VH11+ B cells: a model for natural autoantibody
      producing CD5+ B cells.
AB  - Natural autoantibodies constitute a large portion of serum immunoglobulin M (IgM)
      and bridge the adaptive and innate immune systems, serving as a rapid response to
      common pathogens. Many arise from a distinctive subset of B cells, termed B-1,
      that express CD5. Here, we describe our studies with a representative CD5+ B-cell
      derived natural autoantibody, the VH11Vkappa9 B-cell receptor (BCR) that binds a
      determinant on senescent erythrocytes. This specificity represents 5-10% of the
      CD5+ B-cell subset, with a large portion accounted for by two novel BCRs,
      VH11Vkappa9 and VH12Vkappa4. We have found that the development of B-lineage
      cells with a VH11 rearrangement is surprisingly restricted at several crucial
      bottlenecks: (i). one of the most common VH11 rearrangements generates a heavy
      chain protein that only inefficiently assembles a pre-BCR, key for recombinase
      activating gene downregulation/allelic exclusion and pre-B-clonal expansion;
      (ii). cells containing VH11- micro chains lacking N-addition are favored for
      progression to the B-cell stage, eliminating most bone marrow VH11
      rearrangements; and (iii). only a subset of Vkappa-light chains combine with VH11
      heavy chain to foster progression to the mature B-cell stage. Together, these
      constrain VH11 generation to fetal development and may favor production of B
      cells with the prototype VH11Vkappa9 BCR.

PMID- 14962188
TI  - Mechanisms of selection mediated by interleukin-7, the preBCR, and hemokinin-1
      during B-cell development.
AB  - Many of the stromal-derived signals and factors that regulate B lymphopoiesis
      have been identified. We review recent evidence from our laboratory that shows
      that there are at least three phases during B-cell development when cells direct
      their own maturation, independent of stromal cells. Following the expression of
      the preB-cell receptor (preBCR), cells acquire the ability to proliferate in low
      levels of interleukin-7 (IL-7), which acts as a self-selecting mechanism to
      expand cells that have successfully expressed a preBCR in environments that are
      non-permissive to preBCR- cells. Second, the preBCR is required for a contact
      mediated event between B-cell progenitors. Disruption at this stage prevents the
      further maturation of progenitors to the lipopolysaccharide (LPS)-responsive
      stage. Finally, the transition from IL-7 receptor to mature antigen receptor
      based signaling is enhanced by a novel member of the tachykinin family, hemokinin
      1. This series of maturation, survival, and differentiation signals is generated
      by B-lineage cells as they progress through developmental checkpoints on the way
      to becoming functionally mature cells.

PMID- 14962189
TI  - Peripheral B-cell maturation: the intersection of selection and homeostasis.
AB  - B cells complete maturation after migrating to the periphery, where they transit
      several intermediate developmental stages prior to recruitment into the long
      lived primary pool. Because B-lineage commitment is not regulated by peripheral
      pool size and most peripheral B cells are quiescent, the primary factors
      governing steady-state numbers are the proportion of immature B cells surviving
      transit through later developmental stages and the longevity of mature B cells
      themselves. Substantial evidence indicates that the B-cell receptor (BCR) plays
      an essential role in all these processes, but recent findings suggest a central
      role for the recently described tumor necrosis factor (TNF) family member, B
      lymphocyte stimulator (BLyS). Signaling through one of the BLyS receptors, BLyS
      receptor 3 (BR3), controls B-cell numbers in two ways: by varying the proportion
      of cells that complete transitional B-cell development and by serving as the
      primary determinant of mature B-cell longevity. The recent discovery that BCR
      signaling is selectively coupled to BR3 expression in a developmentally regulated
      fashion links BCR- and BLyS-mediated events, suggesting that specificity-based
      selection and survival may be mechanistically similar processes.

PMID- 14962190
TI  - B-cell homeostasis, competition, resources, and positive selection by self
      antigens.
AB  - In adult mice, the number of B lymphocytes remains constant under homeostatic
      control, in spite of the fact that B cells are produced continuously in numbers
      that largely exceed the number required to replenish the peripheral pools. It
      follows that each newly formed lymphocyte can only persist if another lymphocyte
      dies. In an immune system where the total number of cells is limited, cell
      survival is no longer a passive phenomenon but rather a continuous active process
      where each lymphocyte must compete with other lymphocytes to survive.
      Consequently, the number and the life expectancy of a B-cell clone vary according
      to the presence or absence of competitor populations. This process of lymphocyte
      competition is likely controlled by a common need for resources that are in
      limited supply. The number of peripheral B-cells varies according to the
      availability of B-cell receptor (BCR) ligands. Indeed, it is possible to modify
      steady-state B-cell numbers by antigen manipulation. Moreover, conventional self
      reactive B cells can undergo positive selection. We showed that the fate of a
      self-reactive B cell is determined by the quantity of self-antigens, the number
      of antigen-specific receptors engaged, and its overall antigen-binding avidity
      rather than the affinity of individual BCRs.

PMID- 14962191
TI  - B-cell homeostasis: digital survival or analog growth?
AB  - Maintenance of B-lymphocyte homeostasis requires balanced cell production, death,
      and proliferation. To coordinate these processes, B cells are dependent on cell
      extrinsic signals. In lymphocyte development, precursor cells are dependent on
      Fms-like tyrosine kinase ligand 3 (Flt3L), and pre-B cells are dependent on the
      cytokine interleukin-7. Transitional B cells require B-lymphocyte stimulator
      (BLyS) for survival. Mature B cells require B-cell receptor (BCR) signals and
      also remain sensitive to their microenvironment. An emerging model suggests that
      extrinsic signals do not regulate B-cell survival through a digital mechanism
      where cells are simply instructed to survive or die. Instead, availability and
      competition for extrinsic signals regulates cellular physiology and metabolism in
      an analog fashion that then influences cell commitment to apoptosis or
      proliferation. Decreases in cellular metabolism may sensitize cells to activation
      and action of the pro-apoptotic Bcl-2 family members, Bak and Bax, and promote
      apoptosis. In contrast, increases in metabolism may predispose cells to
      proliferate. Analog control of cell physiology can, thus, be integrated with
      other inputs by individual cells to produce a fate decision for survival,
      proliferation, or apoptosis and prevent diseases of cell death, such as
      immunodeficiency, and cell activation and proliferation, such as autoimmunity or
      cancer.

PMID- 14962192
TI  - Modulation and function of caspase pathways in B lymphocytes.
AB  - During their development, B-lineage cells are selected to mature, to die, to
      divide, or to survive and wait, ready to respond to external signals. The
      homeostatic balance between growth, death, and survival is mediated by signaling
      pathways through the B-cell antigen receptor (BCR) complex, cytokine and
      chemokine receptors or cell-cell coreceptor interactions. The BCR complex is a
      master regulator essential at key checkpoints during development. These
      checkpoints involve various processes, including negative selection (deletion),
      anergy, receptor editing, and positive selection. Without BCRs or downstream BCR
      signaling components, B-lineage cells arrest during development. Removal of BCRs
      from mature B cells leads to their death. Here, we discuss signaling pathways in
      B cells that activate members of the caspase family of cysteine proteases. In
      some B-cell subsets, BCR signaling activates caspases, which in turn induce a
      program leading to cell death. However, in other contexts, caspases are involved
      in the proliferation of B cells. The outcome depends in part on the presence or
      absence of modifiers that affect signaling thresholds and on which caspases are
      activated. These mechanisms allow the coordinated regulation of proliferation and
      apoptosis that is essential for lymphoid homeostasis.

PMID- 14962193
TI  - Alternative routes to maturity: branch points and pathways for generating
      follicular and marginal zone B cells.
AB  - Positive and negative selection of developing B cells is critical for generating
      a functional non-pathogenic B-cell repertoire. Newly formed B cells in the bone
      marrow or peripheral lymphoid system can be eliminated by one of several negative
      selection mechanisms or recruited through a poorly understood positive selection
      mechanism. In this review, we focus on the growing literature on the relevance of
      immature (transitional) peripheral B cells to the area of B-cell positive
      selection, with an emphasis on the notion that transitional B cells can be
      subdivided into several functionally distinct subpopulations. In this discussion,
      we consider the nature of these transitional B-cell subsets and their relevance
      to selection events that influence whether developing B cells eventually give
      rise to follicular versus marginal zone B cells. In addition, we attempt to
      initiate a resolution of current controversies surrounding transitional B-cell
      subsets and offer an alternative model of peripheral B-cell maturation and the
      follicular versus marginal zone decision.

PMID- 14962194
TI  - Signaling in transitional type 2 B cells is critical for peripheral B-cell
      development.
AB  - Splenic peripheral B-cell development and the events regulating this functionally
      significant but relatively poorly defined developmental process have become a
      major focus in recent studies in B-cell immunology. Following the exit from the
      bone marrow, peripheral B cells develop through transitional type 1 (T1) and
      transitional type 2 (T2) B-cell stages. Emerging data suggest that the T2 subset
      is the immediate precursor of the mature B-cell populations present in the
      spleen. In this review, we first elaborate on the evidence describing the unique
      properties of CD21hiCD24hiCD23hiIgMhiIgDhi T2 B cells. T2 cells uniquely activate
      a proliferative, pro-survival, and differentiation program in response to B-cell
      antigen receptor (BCR) engagement. The potential mechanisms leading to the
      differential BCR responsiveness of T1 versus T2 B cells are discussed. We also
      review evidence that distinguishes key BCR-dependent signaling pathways operative
      in T2 and mature B cells. These signaling cascades include a protein kinase Cbeta
      (PKCbeta)-dependent cell-survival pathway and a second PKCbeta-independent
      pathway essential for BCR-driven differentiation. Finally, we discuss recent
      intriguing results suggesting that the type of signal(s) encountered by T2 cells
      leads to their differential maturation toward the follicular mature versus
      marginal zone mature B-cell populations. These combined observations suggest
      important implications with regard to B-cell selection and tolerance, potential
      novel therapeutic targets for B-cell lymphomas, and how the intricate balance of
      commensal organisms and other microenvironmental signals interact to promote the
      generation of 'innate-like' versus adaptive effector B-cell populations.

PMID- 14962195
TI  - Peripheral development of B cells in mouse and man.
AB  - In man and in mouse, B-cell maturation occurs in steps, first in the bone marrow
      from hematopoietic precursors to immature/transitional B cells, then in the
      periphery from transitional to fully mature B cells. Each developmental step is
      tightly controlled by the expression and function of the B-cell receptor (BCR)
      and by the ability to interact with the microenvironment. Mature B cells
      collaborate with T cells in the adaptive immune response, leading to the
      production of high-affinity antibodies. This response is very accurate, but slow.
      Immediately after pathogen entry, however, antibodies already present in the
      serum reinforce the innate immune response and contribute to the first-line
      defense against infection. Low-affinity natural antibodies are produced by B-1a B
      cells in the mouse and immunoglobulin M (IgM) memory cells in man. These
      antibodies represent an immediate protection against all microorganisms and the
      only one against encapsulated bacteria. B-1a and IgM memory B cells may function
      as a link between the innate and adaptive immune response and thus perform a
      primordial B-cell function.

PMID- 14962196
TI  - Development and selection of marginal zone B cells.
AB  - It is now clear that functionally distinct subsets of mature peripheral B cells
      exist. Of these subsets, marginal zone (MZ) B cells in the spleen are
      strategically positioned at the blood-lymphoid interface and are programmed to
      initiate a fast and intense antibody response to blood-borne viral and bacterial
      agents. Their ability to respond vigorously to antigen and polyclonal activators
      make MZ B cells key players in the early response to pathogens in the
      bloodstream. The specialized functions of these innate-like lymphocytes bridge
      the gap between the early innate immune response and the slower adaptive antibody
      response, affected mainly by the more prolific follicular B cells. MZ B cells,
      like B1 cells, are important not only to combat infections but also in the
      maintenance of host homeostasis. Here we discuss some aspects of MZ B-cell
      selection and function in health and disease.

PMID- 14962197
TI  - Positive selection and lineage commitment during peripheral B-lymphocyte
      development.
AB  - Although it is appreciated that the antigen receptor on B cells is required for
      peripheral B-lymphocyte development and survival, it has been unclear whether
      this receptor interacts with self-antigens during development or if it signals
      constitutively in an antigen-independent fashion. The analysis of mutant mice in
      which antigen receptor signaling in B cells is either attenuated or enhanced has
      revealed the existence of a follicular versus marginal zone B-lymphocyte cell
      fate decision. These analyses indicate that weak antigen receptor-derived signals
      favor marginal zone B-cell generation, and relatively strong signals favor the
      development of mature follicular B cells. Even stronger signals derived from the
      antigen receptor favor the generation of B1 B cells. This signal strength model
      for B-cell development supports the notion that self-antigens of varying affinity
      may mediate positive selection and lineage commitment. Direct evidence supporting
      such a view has been obtained from the analysis of antigen receptor knockin mice.
      Specific antigen receptors guide B cells to develop into specific lineages.
      Although Notch-2, nuclear factor-kappaBp50, and other genes are essential for
      marginal zone B-cell development, instructive signals delivered by the antigen
      receptor represent the primary force driving positive selection and lineage
      commitment in B lymphocytes.

PMID- 14962198
TI  - Tolerance-induced receptor selection: scope, sensitivity, locus specificity, and
      relationship to lymphocyte-positive selection.
AB  - Receptor editing is a mode of immunological tolerance of B lymphocytes that
      involves antigen-induced B-cell receptor signaling and consequent secondary
      immunoglobulin light chain gene recombination. This ongoing rearrangement often
      changes B-cell specificity for antigen, rendering the cell non-autoreactive and
      sparing it from deletion. We currently believe that tolerance-induced editing is
      limited to early stages in B-cell development and that it is a major mechanism of
      tolerance, with a low-affinity threshold and the potential to take place in
      virtually every developing B cell. The present review highlights the
      contributions from our laboratory over several years to elucidate these features.

PMID- 14962199
TI  - The molecular basis and biological significance of VH replacement.
AB  - First observed in mouse pre-B-cell lines and then in knock-in mice carrying self
      reactive IgH transgenes, VH replacement has now been shown to contribute to the
      primary B-cell repertoire in humans. Through recombination-activating gene (RAG)
      mediated recombination between a cryptic recombination signal sequence (RSS)
      present in almost all VH genes and the flanking 23 base pair RSS of an upstream
      VH gene, VH replacement renews the entire VH-coding region, while leaving behind
      a short stretch of nucleotides as a VH replacement footprint. In addition to
      extending the CDR3 region, the VH replacement footprints preferentially
      contribute charged amino acids. VH replacement rearrangement in immature B cells
      may either eliminate a self-reactive B-cell receptor or contribute to the
      generation of self-reactive antibodies. VH replacement may also rescue non
      productive or dysfunctional VHDJH rearrangement in pro-B and pre-B cells.
      Conversely, VH replacement of a productive immunoglobulin H gene may generate non
      productive VH replacement to disrupt or temporarily reverse the B-cell
      differentiation process. VH replacement can thus play a complex role in the
      generation of the primary B-cell repertoire.

PMID- 14962201
TI  - Home management of haemophilia.
AB  - The demonstrated benefits of home care for haemophilia include improved quality
      of life, less pain and disability, fewer hospitalizations, and less time lost
      from work or school. Although reduced mortality has not been demonstrated, the
      substantial increase in longevity since the early 1980s correlates with the
      introduction of home treatment and prophylaxis programmes. These programmes must
      be designed and monitored by haemophilia treatment centres (HTC), which are
      staffed with professionals with broad and complementary expertise in the disease
      and its complications. In return, patients and their families must be willing to
      accept the reciprocal responsibilities that come from administering blood
      products or their recombinant equivalents at home. Patients with inhibitors to
      factors VIII or IX pose special challenges, but these complications do not
      obviate participation in home care programmes. Home care was an essential
      prerequisite to the introduction of effective prophylactic factor replacement
      therapy. Prophylaxis offers significant improvements in quality of life, but
      requires a substantial commitment. The use of implantable venous access devices
      can eliminate some of the difficulty and discomfort of peripheral venous access
      in small children, but brings additional risks. The future holds the promise of
      factor concentrates for home use that have longer half-lives, or can be
      administered by alternate routes. Knowledge of patient genotypes may allow
      treatments tailored to avoid complications such as inhibitor development. Gene
      therapy trials, which are currently ongoing, will ultimately lead to gene-based
      treatments as a complement to traditional protein-based therapy.

PMID- 14962202
TI  - Central venous access devices in haemophilia.
AB  - Central venous access devices (CVADs) can facilitate repeated and/or urgent
      administration of coagulation factors in haemophilic patients. We conducted a
      systematic review and meta-analysis of complication rates and risk factors for
      poor outcome. Forty-eight studies with a total of 2704 patients and 2973 CVADs
      were included. The primary indications for CVADs were immune tolerance therapy
      (34.9% of patients), difficult venous access (31.8%) and prophylaxis (29.1%).
      Fully implanted CVADs were employed in 77.4% of cases and external CVADs in
      22.6%. A total of 1190 infections were reported, and the pooled incidence of
      infection was 0.66 per 1000 CVAD days [confidence interval (CI), 0.44-0.97 per
      1000 CVAD days]. Among patients developing infection, the pooled time to first
      infection was 295 days (CI, 181-479 days). Presence of inhibitors was an
      independent risk factor for infection with an incidence rate ratio (IRR) of 1.67
      (CI, 1.15-2.43). Infection was less likely in patients >6 years of age (IRR,
      0.46; CI, 0.27-0.79) and recipients of fully implanted CVADs (IRR, 0.31; CI, 0.12
      0.86). Available information on thrombosis was limited, with only 55 cases being
      reported. Eventually, 31.3% of CVADs were removed, and infection was the reason
      for removal in 69.9% of cases and thrombosis in 4.1%. The pooled time period
      CVADs remained indwelling prior to removal or the expiration of the study
      observation period was 578 days per CVAD (CI, 456-733 days per CVAD). CVADs can
      confer major benefits in patients with haemophilia requiring long-term venous
      access, and serious complications are rare.

PMID- 14962203
TI  - Secondary prophylaxis therapy: what are the benefits, limitations and unknowns?
AB  - Prophylaxis is widely recommended for the management of severe haemophilia A.
      Adoption of this approach has varied from country to country, and notably in the
      US prophylaxis is currently administered in fewer than one-half of severe cases.
      One implication is that a substantial segment of the severe haemophilia. A
      population will only be able to reap the potential benefits of prophylaxis if
      administered in the form of secondary prophylaxis. This therapeutic alternative
      has been less extensively investigated than primary prophylaxis, but nevertheless
      sufficient evidence has been reported to allow an assessment of the benefits and
      limitations of secondary prophylaxis. This evidence addresses the use of
      secondary prophylaxis in three contexts: (i). early secondary prophylaxis; (ii).
      delayed secondary prophylaxis and (iii). secondary prophylaxis in adults. In
      patients receiving early secondary prophylaxis studies in Sweden, the
      Netherlands, the UK and the US have demonstrated a reduction in the frequency of
      bleeding episodes and a subsequent low incidence of arthropathy. Additional
      reported benefits consist of reduced emergency room visits and hospitalizations.
      However, secondary prophylaxis is associated with an increased risk of the
      eventual development of arthropathy compared with primary prophylaxis. When
      delayed until school age or adolescence or until the development of frequent
      bleeding episodes under on-demand treatment, secondary prophylaxis generally
      appears to be unable to reverse all existing or developing joint damage.
      Nevertheless, multiple studies have shown that this therapy can retard further
      joint deterioration, reduce the frequency of haemorrhage, hospitalization and
      missed school days, improve physical function and capacity for self care, lessen
      restrictions on activities, reduce pain and enhance quality of life. Secondary
      prophylaxis in adults has been shown effective in reducing bleeding episodes.
      Adults under secondary prophylaxis can also experience improvements in joint
      condition, functional capacity and quality of life and a reduction in pain.
      Irrespective of age at initiation, long-term secondary prophylaxis appears to
      reduce the frequency of bleeding episodes even in patients with existing target
      joints whose bleeding diathesis persists during the early phases of secondary
      prophylactic therapy. In light of its potential benefits for substantial numbers
      of patients with severe haemophilia A, secondary prophylaxis should be considered
      to as a therapeutic option for patients not receiving primary prophylaxis.

PMID- 14962204
TI  - Trends in clinical management of women with von Willebrand disease: a survey of
      75 women enrolled in haemophilia treatment centres in the United States.
AB  - OBJECTIVE: To assess the management of women with von Willebrand disease( vWD) in
      an Heamophilia Treatment Center (HTC) setting. METHODS: A total of 75 women with
      vWd who were registered in HTCs in the United States participated in this study.
      A telephone interview elicited information about symptoms pertaining to bleeding
      disorders, diagnostic issues, referral patterns, treatment modalities before and
      after the enrollment in the HTC, HTC services provided, and satisfaction with
      care in the HTC. RESULTS: Menorrhagia was the most commonly reported symptom
      (84%). The average time from the first symptom until clinician recognition was 16
      years (range 0-39). In HTC, DDAVP was the most commonly used drug (31%). Of the
      75 women, 71 reported a strong positive opinion and satisfaction about their care
      in the HTCs. DISCUSSION: Women with VWD were typically diagnosed with the
      condition well into adulthood, in spite of the fact that majority of them
      experienced several bleeding symptoms beginning in early childhood. In general an
      HTC setting is appropriate for management of women with bleeding disorders.
      Diagnosis, treatment and education provided in the HTCs were viewed positively by
      those surveyed.

PMID- 14962205
TI  - Bleeding manifestations in males with von Willebrand disease.
AB  - von Willebrand disease (vWD) is the most common congenital bleeding disorder in
      the USA, affecting 1-3% of the population. Previously characterizing the bleeding
      symptoms in females with type 1 vWD, we evaluated 42 males with type 1 vWD, mean
      age 16 years (1-64), of whom 24 (57%) presented with bleeding symptoms. The most
      common initial symptom was postoperative bleeding (26%). The most common bleeding
      symptoms ever were epistaxis (53%), bruising (50%), postoperative bleeding (47%),
      haematomas (29%) and oral bleeding (29%). Of postoperative bleeding,
      ear/nose/throat (44%), dental (17%) and circumcision bleeding (22%) occurred at a
      median 10 years of age, despite a previous bleeding or family history in 89%.
      Complications included anaemia in five (12%), neurological sequelae after
      subdural haematoma and tonsillectomy in two (5%), transfusion-associated
      hepatitis C in two (5%) and degenerative joint disease after traumatic
      haemarthroses in one (2%). The bleeding time (BT) was prolonged in 83%, and the
      ristocetin cofactor (vW:RCoF) and factor VIII (FVIII:C) decreased in 64% and 43%,
      respectively. Haemarthroses and haematoma formation were associated with a longer
      activated partial thromboplastin time (APTT) (P < 0.05), and anaemia with a lower
      FVIII:C (P < 0.05). In 81%, a haemostatic response occurred with 1-8 deamino-d
      arginine vasopressin (DDAVP), although, in 13%, surgical intervention was also
      required to achieve haemostasis. Postoperative bleeding could have been avoided
      in 89%, if a preoperative past bleeding history or family history had been
      obtained, and, in at least 94%, if a preoperative BT and APTT had also been
      performed. The failure to avoid postoperative bleeding and related complications
      in patients with vWD by taking a personal and family bleeding history constitutes
      a major public health problem.

PMID- 14962206
TI  - Treatment of acquired haemophilia with factor eight inhibitor bypassing activity.
AB  - Haemorrhagic manifestations in patients with acquired haemophilia can be fatal if
      not recognized and treated appropriately. A retrospective analysis of the
      efficacy of factor eight inhibitor bypassing activity (FEIBA) in patients with
      acquired haemophilia treated in three medical centres in the past 10 years was
      conducted. The median inhibitor titre at treatment was 128 Bethesda Units (BU) in
      patients with severe and 34 BU in patients with moderate bleeding; P = 0.001. The
      majority of patients received FEIBA at a dose of 75 u kg-1 every 8-12 h. The
      number of FEIBA doses administered was higher in patients with severe compared
      with moderate haemorrhage, 10 vs. 6 doses per bleeding episode; P = 0.001.
      Complete response (CR) was achieved in 76% of severe and 100% of moderate
      bleeding episodes with a total CR of 86%. When compared with patients with human
      inhibitor titre <50 BU, those with titre >51 BU at treatment had lower median
      porcine titre, 1 vs. 9.5 BU; P < 0.05, fewer doses of FEIBA, 6 vs. 8.5 doses; P <
      0.05, and shorter time to CR, 29 vs. 42 h; P < 0.05. Patients exposed to factor
      VIII concentrates prior to FEIBA had significantly higher maximum recorded human
      inhibitor titre compared with patients without such exposure, 273 vs. 38 BU; P =
      0.0001. Treatment with FEIBA was very well tolerated and with very few side
      effects. This study provides evidence that FEIBA is an effective agent in
      acquired haemophilia and suitable for all types of patients regardless of
      severity of haemorrhage, underlying disease or inhibitor titre.

PMID- 14962207
TI  - Activated prothrombin complex concentrate (FEIBA) treatment during surgery in
      patients with inhibitors to FVIII/IX.
AB  - Non-activated and activated prothrombin complex concentrates (PCC/aPCC) have been
      used successfully to treat bleeds in haemophilia patients with inhibitors, but
      most physicians do not consider these products as effective as factor VIII/IX
      (FVIII/IX) concentrates in non-inhibitor patients. Thus, surgical procedures in
      inhibitor patients have been performed reluctantly. We have performed 14 minor
      and five major surgical and invasive diagnostic procedures in eight patients with
      congenital haemophilia A and inhibitors and in two patients with acquired
      haemophilia. When a loading dose of 100 U kg-1 of FEIBA was given followed by 200
      U kg-1 day-1 in three divided doses every 8 h for 3 days, and then, when the
      daily dose was tapered to 100-150 U kg-1, no severe or unexpected bleeding
      complications were observed. However, one adverse event was observed. A 69-year
      old man who suffered a myocardial infarction the third postoperative day
      following sigmoidectomy was managed safely with opiate analgesia, nitrates and
      diuretics, and the continued use of FEIBA(R).

PMID- 14962208
TI  - Excision of pseudotumour in a patient with haemophilia A and inhibitor managed
      with recombinant factor VIIa.
AB  - We describe a patient with haemophilia A and factor VIII inhibitor who underwent
      surgical excision of a large pseudotumour in the left femoral region. Haemostasis
      was successfully maintained with bolus doses of recombinant factor VIIa at 2-h
      intervals and anti-fibrinolytic therapy, and the pseudotumour was removed.
      Subsequently, the dose interval was gradually prolonged to 8 h for a total of 18
      days. Although a spontaneous haemorrhage was observed on postoperative day 8,
      haemostasis was achieved by reducing the dosage interval. No adverse event
      occurred during the course of treatment.

PMID- 14962209
TI  - Successful use of recombinant factor VIIa for severe surgical liver bleeding in a
      5 month-old baby.
AB  - A 5 month-old baby developed non-ceasing intra-peritoneal bleeding after
      extensive surgical biopsy for an hepatoblastoma. A single recombinant activated
      factor VII injection following enlarged hepatectomy helped to resolve quickly
      this life-threatening haemorrhagic syndrome.

PMID- 14962210
TI  - Cranial pseudotumour in haemophilia.
AB  - Intracranial pseudotumour has rarely been reported in haemophilia. We present the
      fourth case describing this complication.

PMID- 14962211
TI  - The spectrum of myositis ossiticans in haemophilia.
AB  - Myositis ossificans (MO) refers to non-neoplastic heterotopic soft tissue
      ossification that can have several aetiologies. Broadly it can be classified into
      three categories based on aetiology [1]. MO traumatica, the most common form
      occurs secondary to acute or chronic trauma. MO can also be associated with
      neurological disorders and in rare cases is congenital. The latter (progressive
      MO) is a genetic disorder in which congenital osseous abnormalities are
      associated with progressive soft tissue calcification. Despite an increased
      tendency to soft tissue bleeds, MO has been rarely reported in haemophilia. We
      treated three adolescents with haemophilia and MO of varying degrees of severity
      and outcome.

PMID- 14962212
TI  - Factor VIII gene intron 1 inversion: lower than expected prevalence in Italian
      haemophiliac severe patients.

PMID- 14962213
TI  - Reported inhibitor incidence in FVIII PUP studies: comparing apples with oranges?

PMID- 14962214
TI  - HIV and HCV coinfection in haemophilia.
AB  - A substantial number of haemophilic patients are infected with both human
      immunodeficiency virus (HIV) and hepatitis C (HCV). HIV has been shown to
      accelerate the course of HCV chronic liver disease and there is evidence that HCV
      infection may worsen the prognosis of HIV. As many HIV infected patients are
      stable on highly active antiretroviral therapy (HAART) HCV should be actively
      managed in coinfected individuals. Pegylated interferon (Peg-IFN)/ribavirin
      combination therapy is the treatment of choice for HCV infection and should be
      considered in patients with stable HIV on or off HAART with CD4 counts >200 x
      10(6)/l. Results of on-going trials of combination therapy in coinfected
      individuals are awaited. For coinfected patients with end stage liver disease who
      are stable on HAART liver transplantation should be considered.

PMID- 14962215
TI  - An economic model of haemophilia in Mexico.
AB  - A model was developed to assess the lifetime costs and outcomes associated with
      haemophilia in Mexico. A retrospective chart review of 182 type A haemophiliacs
      was conducted for patients aged 0-34 years receiving one of three treatments: (i)
      cryoprecipitate at clinic; (ii) concentrate at home; or (iii) concentrate at
      clinic. Patients treated at home experienced 30% less joint damage, used 13-54%
      less factor VIII, had four times fewer clinic visits, and utilized half as many
      hospital days than those treated at a clinic. For cryoprecipitate at clinic
      patients, the annual incidence rates of HCV and HIV were calculated to be 3.6%
      and 1.4% respectively. The life expectancy for patients receiving cryoprecipitate
      and those receiving concentrate was estimated to be 49 years and 69 years
      respectively, with 58% of cryoprecipitate patients predicted to die of AIDS
      before age 69. Across the lifespan, the average annual cost of care was US$11,677
      (MN$110,464) for cryoprecipitate at clinic patients, US$10,104 (M$95,580) for
      concentrate at home patients and US$18,819 (MN$178,027) for concentrate at clinic
      patients. Using a 5% discount rate, the incremental lifetime cost per year of
      life added for treatment with concentrate at home compared with cryoprecipitate
      at a clinic was US$738 (MN$6981). Rank order stability analysis demonstrated that
      the model was most sensitive to the cost of fVIII. These results indicate that
      treatment with concentrate at home compared with cryoprecipitate at a clinic
      substantially improves clinical outcomes at reduced annual cost levels.

PMID- 14962216
TI  - Modelling haemophilia epidemiology and treatment modalities to estimate the
      unconstrained factor VIII demand.
AB  - The article presents a new method for estimating the unconstrained factor VIII
      (FVIII) demand based on the principles of decision analysis. Epidemiology and
      treatment modalities were integrated into a model for unconstrained FVIII demand.
      Assumptions for each variable with impact on the unconstrained FVIII demand were
      defined and probability estimates for these variables were obtained from the
      literature and medical experts. The sensitivity of the unconstrained FVIII demand
      to each of the variables was determined, and the variables with the greatest
      impact were modelled probabilistically. The probability-weighted average for the
      unconstrained FVIII demand model was 6.9 units per capita with a 90% uncertainty
      interval of 2.7-13.6 units per capita. When compared with FVIII usage in
      countries, only Luxembourg's use of FVIII (7.7 units per capita) exceeded the
      probability-weighted average for the modelled unconstrained FVIII demand. As
      better information becomes available, revision of model variables is easily
      accomplished allowing for a more accurate and dynamic forecast of demand over
      time. More accurate modelling of the 'true' demand longitudinally should help
      prevent shortages of FVIII concentrates such as those that have occurred in the
      past. In addition, a more accurate forecast of FVIII demand will allow national
      health care policy makers to better allocate financial and other resources.
      Sufficient and consistent supply of FVIII concentrates and appropriate financing
      of haemophilia care will allow the clinical benefits of more aggressive treatment
      regimens such as prophylaxis to be realized.

PMID- 14962217
TI  - Frequency and causes of hospitalization in HIV-negative children and adolescents
      with haemophilia A or B and its effect on academic achievement.
AB  - The aim of the study is to determine the causes and frequency of hospitalization
      in HIV-negative boys and adolescents with haemophilia and evaluate their impact
      on academic achievement. One hundred and twenty-six HIV-negative boys and
      adolescents were followed prospectively from 1989-96, at 14 comprehensive
      haemophilia treatment centres. One hundred and fifteen participants with
      haemophilia A or B were included in the investigation. These participants
      contributed an average of 57.8 months of follow-up. There were 203
      hospitalizations in 65 participants and 50 participants were never hospitalized.
      Haemarthroses and soft tissue bleeds accounted for 46 and 44 causes of
      hospitalization. Central line infection was the third most common cause.
      Participants with inhibitor had the majority of central line infections and
      hospitalizations. Intracranial haemorrhage resulted in five hospitalizations in
      two participants. Other causes of bleeding accounted for 22% of hospitalizations.
      The median number of hospitalizations per year was 0.18. Duration of hospital
      stay was significantly related to lower spelling scores. Acute and chronic joint
      problems and soft tissue bleeds still account for the majority of
      hospitalizations. Positive inhibitor status was associated with higher numbers of
      hospitalizations and central line infections. Academic achievement was affected,
      to some degree, by length of hospital stay.

PMID- 14962218
TI  - Development and validation of a measure of disease-specific quality of life in
      young children with haemophilia.
AB  - No disease-specific tool for measuring health-related quality of life (HRQL), an
      important outcome when assessing medical treatment, has been developed for
      children with haemophilia. The goal of this study was to develop a parent
      administered questionnaire for evaluating quality of life (QOL) in paediatric
      haemophilia patients between 2 and 6 years of age. After interviewing physicians
      (5), nurses (5) and parents (10) of children with haemophilia aged between 2 and
      6 years, 92 questions were developed and pilot-tested with parents (44) of
      children with haemophilia to create a 39-question instrument that assessed
      somatic symptoms, physical functioning, sleep disturbance, stigma, social
      functioning, fear/resentment, mood/behaviour, restrictions, treatment upset,
      haemophilia concern and energy level. Reliability and validity were evaluated
      with 103 parents of children with haemophilia and parents of 249 age- and gender
      matched healthy children. Estimates of scale reliability (internal consistency)
      for eight multi-item scales ranged from 0.73 to 0.94. Results showed construct
      validity (correlations with age, severity of haemophilia, treatment type, days
      absent and days confined to bed) and correlated with two general, paediatric
      quality-of-life instruments (Impact on Family Scale and Functional Status II).
      Discriminant validity was demonstrated by comparing scores between patients
      receiving/not receiving prophylactic therapy and between haemophilia patients and
      healthy controls. This disease-specific HRQL measure should be of use in clinical
      trials and general practice to better understand disease and treatment impacts in
      young children with haemophilia.

PMID- 14962219
TI  - Successful treatment for patients with von Willebrand disease undergoing urgent
      surgery using factor VIII/VWF concentrate (Humate-P).
AB  - von Willebrand disease (VWD) is characterized by insufficient von Willebrand
      factor (VWF) activity. It has been proposed that VWF:ristocetin cofactor
      (VWF:RCo) activity may be useful in evaluating the response to VWD treatment in
      patients who require replacement therapy. This prospective, open-label, non
      randomized study evaluated the safety and efficacy of a factor VIII (FVIII)/VWF
      concentrate (Humate-P) used in treatment regimens based on VWF:RCo activity in
      subjects with VWD in situations requiring urgent and necessary surgery. This
      article summarizes the results for 39 subjects with 42 evaluable surgical
      treatment events, 100% of which were rated as excellent/good for overall efficacy
      (achievement of haemostasis). The median loading dose based upon VWF:RCo activity
      was 82.3 international units/kilogram (IU kg(-1); range 32.5-216.8 IU kg(-1)),
      and the median maintenance dose per infusion was 52.8 IU kg(-1) (range 24.2-196.5
      IU kg(-1)) for a median of 3 days (range 1-50 days). The median number of
      infusions per event was 6 (range 1-67 infusions). Three unanticipated adverse
      events (peripheral oedema, extremity pain and pseudo-thrombocytopenia) from two
      surgical treatment events were reported that were potentially treatment-related.
      No serious drug-related adverse events (AEs) were observed, and no thrombotic
      events were reported in this study. This study supports the safety and efficacy
      of the FVIII/VWF concentrate Humate-P for the prevention of surgical haemorrhage
      in patients with VWD when administered in doses calculated in VWF:RCo units.

PMID- 14962220
TI  - External fixators in haemophilia.
AB  - External fixators (EF) are not commonly used for patients with haemophilia. We
      describe the use of EF (Ilizarov, AO- uni- and bi-planar fixators and Charnley
      clamp) in nine patients (mean age: 19.2 years; range: 9-37) with haemophilia for
      the following indications - arthrodesis of infected joints, treatment of open
      fractures and osteoclasis. EF required an average of nine skin punctures [range:
      4-17 were maintained for a period of 15 weeks (range: 8-29.5), without regular
      factor replacement, till bone healing was adequate and were removed with a single
      dose of factor infusion]. The mean preoperative factor level achieved was 85%
      (range: 64-102%). Much lower levels were subsequently maintained till wound
      healing. The average total factor consumption was 430 IU kg(-1) (range: 240-870),
      administered over a period of 17 days (range: 9-44). There were no major
      complications related to EF except in a patient who developed inhibitors. In
      conclusion, EF can be used safely in haemophilic patients who do not have
      inhibitors and does not require prolonged factor replacement.

PMID- 14962221
TI  - Role of epsilon amino caproic acid in the management of haemophilic patients with
      inhibitors.
AB  - We managed bleeding crisis in 10 consecutive severe haemophilic patients with
      inhibitors (eight had an inhibitor level of >5 BU mL(-1)) mainly with the
      antifibrinolytic agent, i.e. epsilon amino caproic acid (EACA). EACA was used by
      local, oral or intravenous routes either in combination or separately. Five
      patients developed inhibitors postoperatively and among the remaining five, four
      had recurrent haemarthrosis or soft tissue bleeds and one patient presented with
      severe gastrointestinal bleeding without demonstrable lesion. In all the
      patients, addition of EACA to their management protocol resulted in stoppage
      and/or reduced frequency of bleeding. In six of 10 patients, the results were
      excellent; of these six patients, five developed inhibitors postoperatively.
      Although a reduction in the frequency of bleeding was observed in patients with
      haemarthrosis and soft tissue bleed, it was not spectacular and the patients
      required additional therapy. Hence the results could be described as poor. No
      patient needed to stop the medicine because of the side-effect of EACA. Symptoms
      like mild nausea and vertigo were seen as the side-effects of this medicine when
      high intravenous dosage was administered. EACA thus appears to be an excellent
      adjuvant therapy for haemophilic patients with inhibitors. Besides its well
      recognized antifibrinolytic activity, EACA may have additional mechanisms of
      action in haemophilic patients with inhibitors. More extensive use of this cheap
      and safe product is warranted in haemophilic patients with inhibitors. If larger
      studies confirm this observation, then using antifibrinolytics will allow
      substantial reduction of FEIBA or activated prothrombin complex (APCC) usage in
      such patients without necessarily increasing the thrombotic complications or
      reduction of the clinical efficacy, when compared with higher dosage of FEIBA or
      APCC alone. This will lead to substantial financial savings in countries where up
      to 35% of severe haemophilia A patients develop inhibitors.

PMID- 14962222
TI  - The economic impact of factor VIII inhibitors in patients with haemophilia.
AB  - The impact on the cost of care for haemophilia patients with inhibitors is not
      well defined. To quantify the effect on health care expenditures associated with
      inhibitors to factor VIII (FVIII) or FIX, we conducted a retrospective cohort
      study examining product use and outcomes in adult and paediatric haemophilia
      patients with and without inhibitors. Twelve patients with inhibitors to FVIII or
      FIX (cases) identified in the haemophilia surveillance system (HSS) at two
      centres were matched on age, severity of haemophilia, and treatment centre to
      haemophilia patients without inhibitors. Patients with HIV or significant liver
      disease were excluded from the study. All eligible non-inhibitor control patients
      were selected for inclusion in the study, resulting in a total of 28 controls. We
      then tracked product usage and hospitalizations from programme entry until 1998
      or loss to follow-up, producing a total database of 184 person-years of
      experience. A descriptive matched analysis was conducted to examine annual
      differences in the cost of product used and hospitalizations. We found that the
      median cost for factor products among haemophilia patients with inhibitors was
      $55,853/year, $2,760 less than comparable haemophilia patients without
      inhibitors. The median number of hospitalizations per year was 1.0 for both
      inhibitor and non-inhibitor patients and the median number of days hospitalized
      was virtually the same. Although these findings do not appear to support the
      belief that there is a substantial increase in the cost of care for haemophilia
      patients with inhibitors, it does document that a few outlier patients can drive
      the cost of treatment for this disease. As the largest component of the cost of
      care is that of factor concentrate, it becomes imperative in the current health
      care environment to better define the true costs and benefits of treatments
      designed to eradicate or manage inhibitors. A careful cost accounting of immune
      tolerance induction (ITI) and other therapeutic strategies, taking into account
      successes and failures and duration and intensity of therapy, should help to
      better define the costs and benefits of such approaches. Methods to identify high
      cost inhibitor patients should be developed so that these strategies may be
      targeted to appropriate candidates.

PMID- 14962223
TI  - West Nile Virus inactivation by the solvent/detergent steps of the second and
      third generation manufacturing processes for B-domain deleted recombinant factor
      VIII.
AB  - West Nile Virus (WNV) was immediately and completely inactivated to below assay
      detection limits upon addition of solvent/detergent (S/D) to intermediate process
      pools of second and third generation B-domain deleted recombinant Factor VIII
      (BDDrFVIII; ReFacto, Wyeth, Cambridge, MA, USA). We verify that the S/D step
      provides robust enveloped virus inactivation (>5 log(10)) and functions as a WNV
      barrier.

PMID- 14962224
TI  - Viral clearance occurs very early during the natural resolution of hepatitis C
      virus infection in persons with haemophilia.
AB  - We studied spontaneous hepatitis C virus (HCV) RNA clearance in 12 haemophilic
      patients. In their earliest anti-HCV positive samples, HCV RNA was undetectable
      in eight patients (66%), positive by polymerase chain reaction (PCR) but negative
      by branched-DNA (bDNA) in three others, and quantifiable by bDNA (4839 IU/mL) in
      only one patient. In contrast, in earliest anti-HCV positive samples from eight
      matched controls who had persistent viremia, HCV RNA was quantifiable by bDNA in
      seven (P = 0.0008) and at higher levels (range 4644-678 515 IU/mL; median 43 532
      IU/mL). From initial HCV infection, HCV RNA cleared in 7 months or less in four
      patients and in 1-2 years in six others. HCV persisted for 5 years before
      clearance in the absence of repeated exposure in one patient. We conclude that
      HCV clearance usually but not always occurs within 1-2 years after infection and
      is more likely in those with lower than in those with higher early viral loads.

PMID- 14962225
TI  - Hepatitis C virus quasispecies in the natural course of HCV-related disease in
      patients with haemophilia.
AB  - Patients with haemophilia show high prevalence of hepatitis C infection but low
      rate of progressive liver disease when they are not co-infected with HIV. The
      balance between host immune system and hepatitis C virus (HCV) variability seems
      to play a major role in the evolution of the HCV-related disease. To address this
      point we have studied, in a group of selected patients with haemophilia, the
      composition and in some cases the evolution, of the highest variable envelope
      gene within the hypervariable region 1 (HVR1) of the HCV, which is the region
      more directly exposed to the host immune response. Five of 12 patients show a
      very high homogeneity of the HVR1 and four of those had severe progressive liver
      disease. These results seem to confirm the major role of the immunity in driving
      the variability of the HCV rather than the high degree of different HCV strains
      to which haemophiliacs have been in touch with, during their long-term
      replacement therapy. Our results seem in keeping with other studies on different
      type of patients, where a low degree of quasispecies variability has been
      demonstrated in relationship with the progression and the severity of their liver
      disease.

PMID- 14962226
TI  - Combination therapy with ribavirin and interferon in a cohort of children with
      hepatitis C and haemophilia followed at a pediatric haemophilia treatment center.
AB  - Nearly all children with bleeding disorders who received factor concentrates
      prior to the late 1980s were infected with hepatitis C. Treatment of adults
      infected with hepatitis C with combination therapy consisting of ribavirin and
      interferon has shown sustained response rates of 30-60%. Little data is available
      on the response of children infected with hepatitis C treated with combination
      therapy, especially those with bleeding disorders. We wish to report a single
      paediatric haemophilia treatment center's results of treatment of adolescents
      with haemophilia and hepatitis C infection with combination therapy. All patients
      followed at the haemophilia treatment center with hepatitis C, who were human
      immunodeficiency virus (HIV) negative and had a measurable hepatitis C viral load
      were eligible. Study patients received at least 6 months of 3 MU interferon-alpha
      via subcutaneous injection three times per week and 1000 mg day(-1) of ribavirin.
      Eleven patients agreed to participate in the study. Three patients had an un
      measurable viral load after 6 months of combination therapy. All three completed
      12 months of medication and continued to remain free of hepatitis C for 12 months
      after discontinuation of therapy. Side-effects of combination therapy were
      significant but tolerable. The sustained response rate in this study is similar
      to the historical response rate seen in adults but less than the other reported
      response rates seen in children treated with combination therapy. Given the
      toxicity of combination therapy, and natural history of hepatitis C infection in
      children, consideration of a liver biopsy to evaluate disease progression prior
      to considering antiviral medications is warranted.

PMID- 14962227
TI  - Prothrombin Shanghai: hypoprothrombinaemia caused by substitution of Gla29 by
      Gly.
AB  - Prothrombin deficiency is a rare bleeding disorder inherited as an autosomal
      recessive trait. In this study, we reported a Chinese family with hereditary
      prothrombin deficiency. The proposita had a prolonged activated partial
      thromboplastin time (APTT, 71.6 s) and prothrombin time (PT, 28.0 s). The
      coagulation factors activities were normal except that prothrombin coagulation
      activity was markedly reduced, and the prothrombin antigen level was moderately
      decreased. Nucleotide sequencing of amplified DNA revealed a novel mutation, Glu
      (GAG) to Gly (GGG) at residue 29, which normally undergoes gamma-carboxylation
      within the Gla domain of prothrombin. The proposita was identified as homozygous,
      while her father, mother and maternal grandmother were heterozygous for the
      mutation. Gla29 has been demonstrated as one of the key residue for Ca2+-binding,
      membrane interaction and biological activity of prothrombin.

PMID- 14962228
TI  - Successful treatment of acquired factor VIII inhibitor with cyclosporin.
AB  - Acquired factor VIII inhibitor causes a rare but life-threatening form of
      bleeding disorder, owing to the formation of auto-antibodies against FVIII.
      Treatment modalities include the use of immunosuppressive drugs such as
      cyclophosphamide and corticosteroids, plasmapheresis and i.v. immunoglobulin. A
      patient with idiopathic acquired FVIII inhibitor presented with serious bleeding
      complications resistant to all the above therapeutic modalities. Treatment with
      cyclosporin, however, resulted in a prompt and complete response. The lack of
      side-effects and the relatively quick response suggest that cyclosporin may be
      tried as front line treatment for patients with acquired FVIII inhibitors.

PMID- 14962229
TI  - Penetrating injury to the heart in a patient with haemophilia.

PMID- 14962233
TI  - Erythropoietin has an anti-myeloma effect - a hypothesis based on a clinical
      observation supported by animal studies.
AB  - Recombinant human erythropoietin (rHuEpo) was introduced into clinical practice
      more than a decade ago, and has been found to be effective in the treatment of
      several types of anemia, including anemia of end-stage renal failure and cancer
      related anemia. No study has suggested that Epo might have an effect on the
      biology of the disease, nor any survival advantage to cancer patients treated
      with Epo for anemia has been reported. Here we report six patients with advanced
      multiple myeloma (MM) with very poor prognostic features, whose expected survival
      was <6 months. All six patients were treated with rHuEpo for their anemia, either
      without any chemotherapy or very mild chemotherapy for a short time. Yet,
      surprisingly they lived for 45-133 months totally from MM diagnosis and 38-94
      months with rHuEpo (with a good quality of life). In fact, one patient, is still
      alive and well, more than 8 yr after chemotherapy was discontinued because of a
      resistant aggressive disease. The course in these six MM patients led us to
      hypothesize that Epo might have an antineoplastic or antimyeloma effect. We
      proceeded and tested that hypothesis in mouse models of myeloma (Mittelman M et
      al., Proc Natl Acad Sci USA 98:5181,2001). In these models we confirmed that
      rHuEpo induced tumor regression in about 50% of the BALB/c mice inoculated with
      MOPC-315 myeloma cells. We then presented evidence that the mechanism is a new
      immune-mediated phenomenon, via activation of CD8+ T cells. Furthermore, evidence
      from the literature supports the antineoplastic effect of Epo. Epo might be used
      as an adjunct immune treatment in various malignant diseases, in addition to the
      current regimens and chemotherapeutic protocols. Future trials should determine
      the role of Epo in myeloma and cancer treatment, besides clarifying concerns
      about the presence of Epo receptors on some tumor cells.

PMID- 14962234
TI  - Arsenic trioxide is effective in the treatment of multiple myeloma in SCID mice.
AB  - OBJECTIVES: Pharmacological concentrations of arsenic trioxide (ATO) and organic
      arsenic melarsoprol induce apoptosis in malignant plasma cells. In an attempt to
      further document the interest of the arsenic in vivo, we treated severe combined
      immunodeficient (SCID) mice transplanted with human myeloma cells by ATO or
      melarsoprol. METHODS: Fifty-two SCID mice were irradiated before intraperitoneal
      (i.p.) injection of plasma cells from five myeloma patients. Engraftment was
      assessed by serial measurement of the human monoclonal immunoglobulin G (HuMIgG)
      concentration in mouse serum. Treatment with ATO (10 microg/g i.p. 5 d a week),
      melarsoprol (30 microg/g i.p. 5 d a week) or phosphate buffer saline was started
      when a sustained growth of the tumor cells was demonstrated. RESULTS: Seventeen
      mice developed the human tumor. A significant decrease in HuMIgG amounts was
      observed in three of five mice of the ATO group, including two that achieved an
      apparent complete remission persisting up to 5 months after ATO discontinuation.
      In these mice, no human plasma cells were detected in tissue samples collected
      postmortem. Soluble human interleukin-6 receptor amount, measured in mice sera as
      a surrogate marker of the plasma cell proliferation, varied in parallel with
      HuMIgG concentration. A significant difference in survival was observed between
      control and ATO treated mice (113 and 158 d, respectively; P = 0.01) whereas no
      difference could be evidenced in control and melarsoprol groups. CONCLUSION:
      Present study confirms in vivo the in vitro effects of ATO on myeloma cells.
      Delayed relapses were observed suggesting that prolonged or maintenance therapy
      has to be considered in future clinical trials. Whether or not this will
      translate into clinically relevant effect of the drug in myeloma patients
      deserves further consideration.

PMID- 14962235
TI  - Interpretation of quality of life scores in multiple myeloma by comparison with a
      reference population and assessment of the clinical importance of score
      differences.
AB  - OBJECTIVES: Without clear guidelines, clinicians and health care providers are
      often uncertain how to interpret (quality of life) QOL scores. To facilitate the
      interpretation, QOL scores of multiple myeloma patients at diagnosis were
      compared with the scores of a reference population, and the clinical significance
      of QOL score differences and of changes in scores over time was assessed.
      METHODS: Data from two prospective Nordic Myeloma Study Group trials (221
      patients <60 yr treated with high dose chemotherapy, and 203 patients >60 yr
      treated with melphalan and prednisone) were analysed. The EORTC QLQ-C30
      questionnaire was used. The results were compared with the scores of an age- and
      gender-adjusted Norwegian reference population (n = 3000), using a regressional
      approach. The magnitude of the observed differences and of score changes during
      follow-up was estimated as effect size [score difference (SD)] and according to a
      subjective rating system as small, moderate or large. RESULTS: At diagnosis, the
      most distressing problems were pain and fatigue, reduced physical functioning,
      limitations in role functioning and reduced overall QOL. These differences from
      the reference population were statistically significant (P < 0.001), and large or
      moderate according to the rating systems. After the start of treatment, small to
      moderate improvement in mean QOL scores were observed for most domains.
      CONCLUSION: Comparison with a reference population eases the interpretation of
      QOL scores and prevents overestimation of symptoms and underestimation of
      subjective treatment response. The agreement between the two methods to evaluate
      the meaning of differences and changes in QOL scores was good.

PMID- 14962236
TI  - Successful treatment of systemic amyloidosis with hepatic involvement and factor
      X deficiency by high dose melphalan chemotherapy and autologous stem cell
      reinfusion.
AB  - Systemic amyloidosis with hepatic involvement is a rare disorder, which is
      characterized by the deposits of amyloid fibrils in the liver. The prognosis is
      poor and the median survival is 13 months. Bleeding problems resulting from
      coagulopathy frequently complicates systemic amyloidosis. We present two patients
      with a severe factor X deficiency and hepatomegaly as the presenting
      abnormalities of systemic amyloidosis. One of the patients was treated with high
      dose melphalan chemotherapy and autologous stem cell reinfusion, resulting in a
      normalization of the liver enzyme tests and the factor X level. The diagnosis and
      treatment of systemic amyloidosis with hepatic involvement and the management of
      the multifactorial coagulopathy in these cases is discussed.

PMID- 14962237
TI  - Treatment of primary orbital lymphomas.
AB  - We present an overview of the treatment and clinical outcome of 15 orbital
      lymphomas, carried out in our center from 1993 to 2002. The surgical approach was
      determined by the location, and type of the lesion. Lateral orbitotomy was
      performed in five laterally located lesions, a transconjunctival approach in five
      medial, basal, extra-, intraconal lesions. Pterional intradural and extradural
      and intradural approaches (three) were used in case of intracranial involvement
      or location in the apex and optic canal. Two lesions of the lid or extraconal
      space were operated via eyebrow incision. Ten patients were diagnosed as
      extranodal marginal zone lymphoma. Diffuse large B-cell lymphoma (DLCL) was
      encountered in two patients, follicular lymphoma (FCL) in two patients, and
      diffuse lymphoplasmacytic/lymphoplasmacytoid lymphoma in one patient. All
      patients except one failed to reveal systemic disease and had a localized orbital
      lymphoma. Twelve of the patients responded to radiation therapy with usually 40
      Gy. Cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy was
      applied in two patients, once in combination with radiotherapy. Local recurrence
      was seen in one patient with FCL. Systemic manifestation occurred in one patient
      with DLCL, undergoing ifosfamide, carboplatin, etoposide chemotherapy with
      complete remission. The course of orbital non-Hodgkin's lymphoma is variable and
      requires a multidisciplinary treatment. Therapeutic options include surgical
      biopsy, radiation therapy, and chemotherapy.

PMID- 14962238
TI  - Growth factor receptor profile of CD34 cells in normal bone marrow, cord blood
      and mobilized peripheral blood.
AB  - Growth factors regulate the proliferation and differentiation of hemopoietic
      cells. Their effect on hemopoietic precursors differs according to the ontogenic
      source of the cells. Cord blood and mobilized blood CD34(+) cells have a higher
      sensitivity for growth factors than bone marrow CD34(+) cells. This could be due
      to a higher expression of growth factor receptors. Therefore, we examined the
      expression of receptors for stem cell factor (SCF), interleukin-6 (IL-6), IL-3,
      granulocyte colony-stimulating factor (G-CSF) and IL-7 on the CD34(+) cells of
      cord blood, mobilized peripheral blood and bone marrow. The receptors were
      detected with monoclonal antibodies and flow cytometry. The majority of the
      CD34(+) cells in bone marrow clearly expressed SCFR; they showed a moderate
      positivity for IL-3Ralpha and a weak staining for G-CSFR and IL-6 Ralpha. Less
      than 10% of the cells were IL-7R positive. Cord blood CD34(+) cells showed a
      higher expression of SCFR and a lower positivity for G-CSFR and IL-6Ralpha.
      Mobilized blood CD34(+) cells showed a lower expression of SCFR and G-CSFR, and a
      higher positivity for IL-3Ralpha. This was not solely due to the presence of more
      myeloid precursors in mobilized blood, as the growth factor receptor profile did
      not correspond to that of early or late myeloid CD34(+) precursors in normal bone
      marrow. Changes induced by the mobilization procedure occurred as well. In
      conclusion, the higher sensitivity for growth factors of hemopoietic precursors
      in cord blood and mobilized blood cannot be explained by a general increase of
      the growth factor receptor expression on the CD34(+) cells.

PMID- 14962239
TI  - Reference values for peripheral blood lymphocyte phenotypes applicable to the
      healthy adult population in Switzerland.
AB  - OBJECTIVES: Use of domestic reference values is known to improve the accuracy of
      flow cytometric analysis by integrating local variation due to race, gender, and
      age. In the absence of previously published estimates, we now report
      establishment of reference values for a wide range of peripheral blood lymphocyte
      phenotypes applicable to the healthy adult population in Switzerland and other
      regions with similar demographic characteristics. METHODS: A representative
      sample population was recruited from among well characterized local blood donors
      (n = 70) and quantitative multiparametric flow cytometry used to estimate
      absolute and proportional values for a range of T-, B-, and NK-cell subsets,
      including those associated with activation and maturity. Distribution-free
      methods were then applied to generate 95% reference values and to estimate the
      significance of gender and age-related differences. RESULTS: Reference values
      were obtained for the absolute and proportional levels of total CD3(+) T cells
      (536-1787 cells/microL, 54.90-84.03%), helper CD4(+) T cells (309-1139
      cells/microL, 32.53-62.88%), cytotoxic CD8(+) T cells (137-823 cells/microL,
      11.55-38.60%), activated CD3(+) T cells expressing CD25 (7-94 cells/microL, 0.50
      5.95%), CD38 (102-554 cells/microL, 5.98-26.80%), HLA-DR (18-186 cells/microL,
      1.25-9.68%) or CD38/HLA-DR (4-52 cells/microL, 0.30-2.30%), activated CD4(+) T
      cells expressing CD25 (7-52 cells/microL, 0.33-2.80%), CD38 (69-547 cells/microL,
      6.13-32.20%), HLA-DR (11-55 cells/microL, 0.80-4.43%) or CD38/HLA-DR (4-22
      cells/microL, 0.30-1.35%), activated CD8(+) T cells expressing CD25 (0-12
      cells/microL, 0.00-0.69%), CD38 (13-124 cells/microL, 0.93-7.03%), HLA-DR (6-108
      cells/microL, 0.33-6.38%) or CD38/HLA-DR (2-47 cells/microL, 0.13-2.68%), naive
      CD4(+) T cells expressing CD45RA(+)/CD62L(+) (84-761 cells/microL, 9.48-41.88%),
      naive CD8(+) T cells expressing CD45RA(+)/CD62L(+) (42-360 cells/microL, 3.68
      19.23%), memory CD4(+) T cells expressing CD45RO(+) (247-807 cells/microL, 16.50
      42.15%), memory CD8(+) T cells expressing CD45RO(+) (72-377 cells/microL, 3.78
      22.80%), B-cells expressing CD19 (72-460 cells/microL, 4.70-19.13%) or CD20 (66
      529 cells/microL, 4.63-21.00%), total CD3(-)/(CD16(+)/CD56(+)) NK-cells (77-427
      cells/microL, 5.35-30.93%), and activated NK-cells expressing CD25 (0-10
      cells/microL, 0-0.50%) or HLA-DR (3-99 cells/microL, 0.20-7.28%). CONCLUSION: It
      is anticipated that availability of localized reference values for an extended
      range of peripheral blood lymphocyte phenotypes should supplement previously
      published reference values and enhance the utility of flow cytometric analysis
      undertaken in Switzerland.

PMID- 14962240
TI  - Effect of low-dose warfarin on D-dimer levels during sickle cell vaso-occlusive
      crisis: a brief report.
AB  - OBJECTIVE: To evaluate the activation of clotting systems in patients with sickle
      cell disease (SCD) by measuring the plasma D-dimer level and to determine the
      effect of low-dose warfarin on D-dimer level during vaso-occlusive crisis.
      METHODS: Plasma D-dimer level was measured in 65 blood samples of 37 adult
      patients with SCD who were hospitalized for vaso-occlusive painful crisis. D
      dimer level of patients who were on low-dose warfarin was compared with those
      patients who were not on any anticoagulation treatment. Analysis of variance
      (anova) was carried out to determine factors significantly associated with low D
      dimer level in patients with SCD. The following factors were included in the
      anova model; warfarin, homozygous hemoglobin S, history of blood transfusion in
      past 3 months, hydroxyurea, hemoglobin S%, hemoglobin F%, white blood cell
      counts, hemoglobin level, platelet count, and plasma fibrinogen level. RESULTS:
      Overall median D-dimer level in 65 samples was 2.7 microg fibrinogen equivalent
      units (FEU)/mL (0.34-4). Patients who were on low-dose warfarin had a median D
      dimer level of 0.81 microg FEU/mL (0.34-1.8) compared with 3.1 microg FEU/mL
      (0.94-4) in those patients who were not on anticoagulation treatment. Using anova
      to model D-dimer levels, only warfarin was significantly correlated with low D
      dimer levels after controlling for other variables. CONCLUSIONS: Patients with
      SCD during vaso-occulsive painful crisis have an elevated D-dimer level. Low-dose
      anticoagulation treatment is associated with a significant reduction in the D
      dimer levels.

PMID- 14962241
TI  - Secondary follicular lymphoma of the bone, transformed into large cell lymphoma,
      in a patient with chronic lymphocytic leukaemia: an uncommon manifestation of
      Richter's syndrome.
AB  - Patients with chronic lymphocytic leukemia (CLL) are at a significantly increased
      risk of developing a second malignant neoplasm in the course of their disease.
      The occurrence of large cell lymphoma [Richter's syndrome (RS)] has been
      described in approximately 3-5% of CLL patients. Other types of secondary
      lymphoid malignancies are extremely rare. Here we describe a patient, heavily
      pretreated, with long history of CLL who developed a secondary follicular
      lymphoma, transformed into a diffuse large cell lymphoma (LCL), with isolated
      manifestation in the bone, a very rare manifestation of RS. CLL and LCL cells
      were of distinct clonal origin, as documented by DNA sequencing of the CDR3
      regions. Twelve months after the completion of chemo- and local radiotherapy, the
      patient is still in remission.

PMID- 14962242
TI  - Successful treatment of oral lesions of chronic lichenoid graft-vs.-host disease
      by the addition of low-level laser therapy to systemic immunosuppression.
AB  - We report a case of severe oral stomatitis caused by lichenoid chronic graft-vs.
      host disease in which low-level laser therapy applied to the oral mucosa, in
      addition to standard systemic immunosuppressive treatment, resulted in quick
      healing and symptomatic relief.

PMID- 14962243
TI  - Association of non-alcoholic steatohepatitis (NASH) with chronic neutrophilic
      leukemia.
AB  - A 54-yr-old female having chronic neutrophilic leukemia (CNL) associated with
      severe liver injury is presented. Physical examination on admission showed severe
      jaundice, hepatosplenomegaly, massive ascites, and pretibial edema. Complete
      blood count showed a hemoglobin level of 9.1 g/dL, platelet count of 25.8 x
      10(4)/microL, and white blood cell count of 36.6 x 10(3)/microL with 89.7%
      neutrophils. Blood chemistry showed hyperbilirubinemia (21.9 mg/dL) with normal
      transaminase levels. There was no abnormality in serum cholesterol, triglyceride,
      or glucose levels. Neutrophil alkaline phosphatase activity was significantly
      elevated. Bone marrow aspiration showed myeloid hyperplasia with normal
      karyotype. Rearrangement of the bcr/abl was not detected by either polymerase
      chain reaction or fluorescence in situ hybridization. Human androgen receptor
      gene assay (HUMARA) of the bone marrow cells showed clonal proliferation of
      neutrophils. The patient was diagnosed as having CNL. To evaluate the
      pathogenesis of the liver injury, a needle biopsy was performed, which showed
      steatohepatitis with infiltration of neutrophils. As the patient had no history
      of alcohol abuse, a diagnosis of non-alcoholic steatohepatitis (NASH) was made.
      Assuming that the infiltration of abnormal neutrophils into the liver contributed
      to the development of NASH, she was treated with cytoreductive chemotherapy
      (cytosine arabinoside: 100 mg/d, 1-3 doses/wk). With decreases in white blood
      cell counts, serum bilirubin levels decreased gradually to 1.5 mg/mL. A
      postchemotherapy liver biopsy specimen showed marked improvement of the fatty
      degenerative change. To our knowledge, this is the first report describing the
      development of NASH in a myeloproliferative disorder. We believe that the
      infiltration of leukemic cells contributed to the development of NASH in this
      patient.

PMID- 14962244
TI  - Usefulness of CD9 detection in the diagnosis of acute megakaryoblastic leukemia.

PMID- 14962245
TI  - Monoclonal antibodies in the treatment of autoimmune cytopenias.
AB  - In recent years, clinical studies have been undertaken with selected monoclonal
      antibodies (MoAbs) in the treatment of several hematological diseases, especially
      in malignant disorders. However, some clinical observations indicate that MoAbs
      may be an important alternative for the conventional therapy of some autoimmune
      disorders. Two MoAbs directed against CD20 antigen (rituximab, Rituxan, Mabthera)
      and CD52 antigen (alemtuzumab, Campath-1H) seem to be especially useful for this
      purpose. Autoimmune cytopenias have been investigated in the last few years with
      positive preliminary results. Rituximab seems to be an effective and safe agent
      for the treatment of immune thrombocytopenias, autoimmune hemolytic anemia, cold
      agglutinin disease and pure red cell aplasia. Although the case series are small,
      rituximab seems to be an effective and safe agent for the treatment of these
      diseases. Clinical experience with alemtuzumab in patients with autoimmune
      cytopenias is even more limited than with rituximab. However, preliminary results
      indicate that further studies with this MoAb are warranted. A longer follow-up
      and the studies on larger number of patients are needed to determine the real
      value of these new approaches in autoimmune cytopenias. Recent experiences with
      the use of MoAbs in treatment of these diseases are the subject of this review.

PMID- 14962246
TI  - Expression and prognostic value of hemopoietic cytokine receptors in acute
      myeloid leukemia (AML): implications for future therapeutical strategies.
AB  - OBJECTIVES: Hemopoietic cytokines regulate hemopoietic cell functions via
      specific cell surface receptors. There is evidence to suggest, that those
      receptors (R) could play a role in leukemia with respect to cell differentiations
      and its regulation, prognosis, and pathobiology. Knowledge of individual cytokine
      receptor (CKR) profiles could provide new discoveries about CKR-supported
      therapeutic considerations. METHODS: We have studied the expression of CKR on
      mononuclear bone marrow (BM) cells of 89 patients with acute myeloid leukemia
      (AML) at first diagnosis, three patients at relapse or with persisting AML and
      eight healthy probands by fluorescence-activated cell sorting (FACS) analysis
      using directly fluorescein-conjugated antibodies: CD114 (hG-CSF-R), CD116 (hGM
      CSF-R), CD117 (hSCF-R), CD123 (hIL-3-R), CD130 (gp130subunit), CD135 (hFL-R). A
      case was defined as positive, if more than 20% of the cells expressed the
      regarding CKR. RESULTS: All investigated CKR were more frequently expressed in
      AML-samples than in healthy BM-samples, except CD130, which was only expressed on
      5-6% of AML-blasts in all and with only one healthy BM-sample being CD130(+).
      Within the French-American-British (FAB) types we observed a maturation- and
      lineage (granulocytic/monocytic)-committed expression profile. Monocytic subtypes
      (FAB-type M4/M5) showed significantly more GM-CSF-R(+) (P = 0.001) and FL-R(+) (P
      = 0.001) and significantly less stem cell factor-R (SCF-R(+)) (P = 0.02) cases.
      Highest proportions of G-CSF-R(+) blasts were observed in FAB-type M3. In
      undifferentiated leukemias (FAB-type M1, M2) high amounts of SCF-R(+), IL-3-R(+),
      and FL-R(+) blasts could be detected. FL-R was the only CKR, which was positive
      in FAB-type M0 (n = 2). No differences in CKR-expression were detected between
      primary (p) and secondary (s). Separating our patient cohorts in cytogenetic risk
      groups we could detect a significant higher proportion of G-CSF-R(+) blasts in
      the cytogenetic good risk group than in the bad risk group (P = 0.027), but G-CSF
      R-expression did not correlate with remission-rate or relapse-free survival
      probability of the patients. For clinical evaluation only patients treated by the
      AML-CG-protocol, were included (n = 53). There were no differences of CKR
      expression in the responder and non-responder group, however, significant lower
      relapse-free survival probabilities for patients with more than 85.5% FL-R(+) (P
      = 0.001) and more than 45.5% SCF-R(+) blasts were found (P = 0.02). Patients with
      more than 32.5% IL-3-R(+) cells also showed a tendency to a lower relapse-free
      survival probability (P = 0.26), whereas patients with more than 33% GM-CSF-R(+)
      (P = 0.06) and patients with more than 52% G-CSF-R(+) (P = 0.175) blasts tended
      to have a higher relapse-free survival probability. CONCLUSION: We can conclude,
      that CKR-expression in AML is maturation- and lineage-committed and the
      proportions of especially early acting CKR have influence on relapse-free
      survival probability of AML-patients, independently of the karyotype. With
      respect to the individual CKR status the benefit of cytokines as priming agents,
      as agents to treat neutropenia or to influence the metabolism of chemotherapy can
      be discussed under new points of view.

PMID- 14962247
TI  - Optimizing donor selection in a cord blood bank.
AB  - OBJECTIVES: The main limitation factor for the wide use of umbilical cord blood
      (UCB) as a source of hematopoietic progenitor for transplantation is cell dose.
      One of the specific areas identified by some studies for improvement of UCB
      collection is donor selection. METHODS: Over a 3-mth period, 391 consecutive
      maternal-neonatal pairs were evaluated during the pre-partum period in the
      maternity ward at La Fe University Hospital (Valencia) by the Cord Blood Bank
      staff. Reasons for discarding umbilical cord blood donors and collected UCB units
      at the Cord Blood Bank in Valencia have been analysed. Obstetric factors
      influencing TNC content of 1300 collected UCB units have been determined, in
      order to establish obstetric criteria for cord blood donors selection in our
      geographic area. RESULTS: Only 32.5% of potential cord blood donors were refused.
      Among 1300 UCB collected, 506 (38.9%) were discarded before cryopreservation,
      mainly due to low cell counts. Multivariate analyses showed that the main
      significant factors influencing nucleated cell count were the weight of the
      placenta, sex of newborn and mode of collection. CONCLUSIONS: Our study shows
      that maternal medical histories must be completely reviewed by medical staff
      before collection of the UCB. Obstetrical factors influence cell content of UCB
      and could be added to standard cord blood donor criteria in order to improve the
      bank efficiency.

PMID- 14962248
TI  - Quality of life and brain function following high-dose recombinant human
      erythropoietin in low-risk myelodysplastic syndromes: a preliminary report.
AB  - OBJECTIVE: In this prospective study we evaluate the effects of high-dose
      recombinant human erythropoietin (rHuEPO) on quality of life (QOL) and brain
      function in patients with low-risk myelodysplastic syndromes (MDS) (<10% marrow
      blasts). Preliminary data are reported. METHODS: Eleven consecutive patients were
      given rHuEPO (40,000 IU two times a week) for 12 wk. Responsive patients
      continued with 40,000 IU/wk for further 12 wk. Changes in QOL were assessed by
      the Functional Assessment of Cancer Therapy-Anemia (FACT-An) self-report.
      Neurophysiological evaluation at the start of the therapy (t0) included duplex
      scanning of neck vessels, transcranial Doppler sonography (TCD), a complex
      neuropsychological evaluation, and quantitative electroencephalography (qEEG).
      Eight patients completed the neurophysiological evaluation after 24 wk (t1).
      RESULTS: Six patients (55%) achieved an erythroid response after 12 wk, which was
      maintained after 24 wk of treatment. FACT-An score showed a relevant improvement
      between t0 and t1 in these patients. At baseline, TCD showed a mean cerebral
      blood flow (CBF) velocity in the upper normal range. Abnormalities in brain
      function were observed in five patients. In the eight patients who were re
      evaluated at t1, improvement was observed in three responding patients, two of
      them with abnormal values at t0. A strict correlation between QOL and
      neurophysiological improvements was not observed. CONCLUSIONS: A high-dose
      induction phase with rHuEPO followed by maintenance therapy may be an effective
      therapeutic schedule for low-risk MDS patients. The erythroid response was
      associated with positive changes in the QOL. Neurophysiological improvements
      occurred only in a part (50%) of responding patients, mainly those who showed
      altered results at baseline.

PMID- 14962249
TI  - Multiplex analysis of the most common mutations related to hereditary
      haemochromatosis: two methods combining specific amplification with capillary
      electrophoresis.
AB  - We present the first application of a multiplex multicolour assay for the
      simultaneous detection of three of the most frequent mutations related to
      hereditary haemochromatosis (C282Y, H63D and S65C), using fluorescent detection
      and capillary electrophoresis. We describe two methods: the first is based on a
      single base extension assay, resulting in a single base difference of the
      extended products; and the second is a competitive allele-specific polymerase
      chain reaction (PCR), based on competition between allele-specific primers.
      Specificity of the latter primers is enhanced with a mismatch at the
      antepenultimate nucleotide. Primers are designed to amplify products of different
      sizes and with different fluorescent dyes in order to accurately distinguish all
      possible combinations of genotypes (homozygous and heterozygous for each
      mutation) in a multiplex PCR analysis. An advantage of the present approach is
      that capillary electrophoresis analysis of the amplified products enables easy,
      rapid, unambiguous and high resolution discrimination between wild-type and
      mutant alleles, although different mutations may be present in the multiplex
      analysis. This will facilitate automated genotyping for routine molecular
      diagnostics and large-scale genetic studies.

PMID- 14962250
TI  - Possible role of cytokine-induced tryptophan degradation in anaemia of
      inflammation.
AB  - Anaemia of inflammation (AI) is a frequent complication in patients suffering
      from chronic inflammatory disorders including infections, autoimmune and
      malignant disease. Cytokine imbalance with a shift towards T-helper (Th)1-type
      immune response seems to be important in the pathogenesis of this type of
      anaemia. Interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha may affect
      the growth and differentiation of erythroid progenitor cells. In macrophages, IFN
      gamma strongly induces indoleamine (2,3)-dioxygenase, an enzyme which degrades
      tryptophan (trp) to kynurenine (kyn). Trp availability is rate limiting for
      protein biosynthesis and thus cell growth, including erythropoiesis. In this
      study, trp and kyn concentrations and their relationship to haemoglobin
      concentrations and to immune activation was examined in 22 patients with AI.
      Patients with AI presented with lower trp concentrations than healthy controls of
      similar age, and a significantly higher kyn to trp ratio, suggesting enhanced trp
      degradation and, because of a positive correlation with neopterin, immune
      activation. The kyn to trp ratio was inversely correlated to haemoglobin levels.
      Thus, the limitation of trp availability to erythroid progenitors may be a key
      mechanism in cytokine-mediated inhibition of erythropoiesis, and the therapeutic
      modulation of indoleamine (2,3)-dioxygenase and trp levels may be promising
      targets for AI therapy.

PMID- 14962251
TI  - Plasma level of the macrophage-derived soluble CD163 is increased and positively
      correlates with severity in Gaucher's disease.
AB  - Recently, soluble CD163 (sCD163) has been identified as a macrophage/monocyte
      specific plasma protein and increased concentrations have been measured in
      patients with infection and myeloid leukaemia. In the present study we
      investigated the levels of sCD163 in patients with Gaucher's disease, an
      inherited lysosomal storage disorder characterised by hepato- and splenomegaly
      due to excessive accumulation of macrophages. The sCD163 plasma levels, median
      (25-75 percentiles), were far above the levels in normal subjects [7.1 mg/L (4.8
      10.3) vs. 1.9 mg/L (1.5-2.4), P < 0.0001]. After initiation of enzyme
      supplementation therapy, the sCD163 levels were significantly reduced [4.7 mg/L
      (3.2-6.6), P = 0.0004]. sCD163 correlated with disease severity (rho = 0.43, P <
      0.0061) and chitotriosidase activity (rho = 0.71, P > 0.0001). This study further
      establishes that sCD163 may be a valuable laboratory parameter in monitoring
      disease with increased macrophage activity.

PMID- 14962252
TI  - Effective high-dose chemotherapy combined with CD34+-selected peripheral blood
      stem cell transplantation in a patient with cutaneous involvement of nasal NK/T
      cell lymphoma.
AB  - The prognosis of nasal natural killer (NK)/T-cell lymphoma with cutaneous
      involvement especially is morbid despite intensive chemotherapy and radiotherapy.
      We treated a 52-yr-old Japanese woman with cutaneous dissemination of nasal NK/T
      cell lymphoma. Six cycles of chemotherapy, irradiation to skin lesion were
      administered and complete remission (CR) was attained. High-dose chemotherapy
      (HDC; etoposide 750 mg/m(2) x 2 d, cyclophosphamide 60 mg/kg x 2 d, total body
      irradiation 12 Gy two daily fractions x 3 d) followed by CD34(+)-selected
      autologous peripheral blood stem cell transplantation (CD34(+)-APBSCT) was then
      prescribed. Complete remission (CR) was obtained and she has been free of disease
      for 34 months since CD34(+)-APBSCT. We suggest that marrow-ablative chemotherapy
      facilitated by autologous stem cell transplantation should be considered part of
      the primary therapy for subjects with a poor prognosis for nasal NK/T-cell
      lymphoma with cutaneous involvement.

PMID- 14962253
TI  - Treatment with campath-1H for relapsed chronic lymphocytic leukemia after
      allogeneic peripheral blood stem cell transplantation does not abrogate the
      development of chronic GVHD.
AB  - The graft vs. leukemia (GVL) effect is one of the most important factors of anti
      tumor activity after allogeneic hematopoetic stem cell transplants (alloSCT). Its
      effectiveness depends mainly on the tumor biology as well as the tumor burden.
      Patients with a high tumor burden may not respond to GVL-effect despite otherwise
      sensitive biology. Campath-1H is known as an effective treatment of chronic
      lymphocytic leukemia (CLL). Due to its ability to induce profound
      immunosuppression, it has also been used as part of conditioning regimens before
      alloSCT. We report a patient, who received campath-1H in combination with
      docetaxel for treatment of chemotherapy and donor lymphocyte infusion resistant
      CLL after alloSCT, who developed shortly after discontinuation of treatment with
      campath-1H severe eosinophilia of the peripheral blood and typical clinical as
      well as histological signs of cutaneous chronic graft vs. host disease followed
      by complete clearance of CLL. The clinical course demonstrates the impact of the
      tumor burden on the GVL-effect, as well as the effectiveness of campath-1H in the
      presence chemo-resistance in a patient with CLL. Furthermore, the GVL effect was
      not abrogated by the use of campath-1H.

PMID- 14962254
TI  - Association of pyoderma gangrenosum and sterile osteomyelitis in a patient having
      myelodysplastic syndrome with der(1;7)(q10;q10).
AB  - Neutrophilic dermatoses such as Sweet's disease and pyoderma gangrenosum (PG) are
      occasionally associated with myelodysplastic syndrome (MDS). We present here a 67
      yr-old male having PG and sterile osteomyelitis in association with underlying
      MDS (refractory anemia) and Crohn's disease. To establish the diagnosis of MDS,
      sternal bone marrow puncture was performed, which showed chromosomal abnormality
      containing der(1;7)(q10;q10). After the puncture, he suffered from gradually
      progressive skin ulceration, flare, and bone pain. Magnetic resonance imaging
      (MRI) of the sternum showed severe inflammation in the sternum and the overlying
      subcutaneous tissue. All of the cultures obtained from the wound were negative
      for both bacteria and fungus. Biopsy was performed from the antero-sternal skin
      lesion, which showed epidermal ulceration with prominent infiltration of
      neutrophils. He was thus diagnosed as having PG and sterile osteomyelitis, and
      was treated with prednisolone, which completely resolved the symptoms. We
      consider that the bone marrow aspiration in the present patient provoked PG and
      sterile osteomyelitis. As was previously reported by others, certain chromosomal
      abnormalities in MDS may be related with the development of neutrophilic
      dermatoses.

PMID- 14962255
TI  - Haemorrhagic infarction of the spleen in a patient with myelofibrosis,
      transforming to AML.

PMID- 14962256
TI  - Clinicopathological correlations of TIMP-1 and TIMP-2 in Hodgkin's lymphoma.
AB  - OBJECTIVES: The influence of matrix-tumour interactions in Hodgkin's lymphoma is
      poorly characterised, although a large part of the tumour often consists of
      reactive tissue. The aim of the present study was to assess the
      clinicopathological role of two main inhibitors of matrix metalloproteinases,
      TIMP-1 and TIMP-2, in Hodgkin's lymphoma. MATERIALS AND METHODS: The TIMP-1 and
      TIMP-2 protein expressions were studied from paraffin-embedded tumour sections of
      68 patients with Hodgkin's lymphoma by using immunostaining with TIMP-1 and TIMP
      2-specific antibodies. The results of the stainings were compared with the
      clinicopathological disease characteristics. RESULTS: A total of 33.3% of the
      tumour tissue sections expressed TIMP-1 and 46.8% expressed TIMP-2. The
      expression of the TIMP-1 protein was found to be strongly associated with the
      nodular sclerosis subtype (P = 0.015) and the existence of a bulky tumour (P =
      0.004) in Hodgkin's lymphoma. The expression of the TIMP-2 protein, on the other
      hand, correlated with the occurrence of B symptoms (P = 0.032). CONCLUSIONS:
      These results provide the first clinical evidence suggesting that TIMP-1 could
      promote growth of Hodgkin's lymphoma, and may be linked to connective tissue
      turnover in the nodular sclerosis subtype. However, TIMP-2 is shown to correlate
      with systemic symptoms.

PMID- 14962257
TI  - Salvage therapy with an outpatient DHAP schedule followed by PBSC transplantation
      in 79 lymphoma patients: an intention to mobilize and transplant analysis.
AB  - Chemotherapy followed by autologous transplantation may be an efficient salvage
      treatment in malignant lymphomas. We investigated the feasibility, tolerability
      and efficacy of an outpatient schedule of dexamethasone, cytarabine and cisplatin
      (DHAP), followed by peripheral blood progenitor cell autografting as salvage
      treatment in patients with high grade (HG), low grade (LG) non-Hodgkin's lymphoma
      (NHL) and Hodgkin's Disease (HD). A total of 159 DHAP courses (median: 2, range:
      1-5), was administered on outpatient basis to 79 patients (31 LG-NHL, 28 HG-NHL
      and 20 HD), with the intention to mobilize and to transplant. A successful
      collection was not achieved in 40% LG-NHL, 10% HD and 20% HG-NHL patients. The
      risk to fail the collection was significantly related to the number of previous
      chemotherapy courses (>6) (P = 0.005, RR = 1.4), to the pretransplant status (P =
      0.04, RR = 13.5) and to the previous fludarabine administration (P = 0.01, RR =
      20). High dose therapy (HDT) was feasible in 60 patients (76%). The overall
      treatment related mortality was 3.8%. The overall response rate (ORR) was 81%
      with a 57.6% overall survival (OS) at 62 months (95% CI: 45-69.3%) and a
      progression free survival (PFS) of 42% at 74 months (95% CI: 26.7-58%). The
      diagnosis of HG-NHL and the non-response to DHAP resulted to reduce respectively
      the OS (P = 0.007, RR = 2.8) and PFS probability (P = 0.01, RR = 4.1). In
      conclusion this outpatient schedule of DHAP is a well tolerated, efficient
      salvage and mobilizing regimen not only in HG-NHL, but also in LG-NHL and in HD.
      Randomized studies are needed to better define the role of DHAP in LG-NHL and HD
      patients.

PMID- 14962258
TI  - Dendritic cell recovery after allogeneic stem-cell transplantation in acute
      leukemia: correlations with clinical and transplant characteristics.
AB  - We have analyzed the kinetics of reconstitution of circulating dendritic cell
      (DC) subsets (myeloid-DC1 and lymphoid-DC2) in 19 patients affected by acute
      leukemia undergoing allogeneic hematopoietic stem-cell transplantation (HSCT). We
      have found that pretransplant DC1 and DC2 were lower in leukemic patients than in
      healthy subjects (P = 0.003 and P = 0.004, respectively) and that the number of
      DC2 (but not DC1) infused with the graft was higher in patients receiving
      peripheral blood stem cells (PBSC) (P = 0.03). Patients recovered to the
      pretransplant DC1 and DC2 levels within day +60; however, a normal DC1 number was
      reached on day +365, while DC2 remained lower than in controls up to 1 yr after
      transplant. DC1 reconstitution did not differ significantly between patients
      receiving bone marrow stem cells (BMSC) or PBSC, while patients receiving PBSC
      presented increased levels of DC2 on day +30 (P = 0.008) and +100 (P = 0.047) and
      a higher number of T lymphocytes and natural killer cells until day +365. The
      occurrence of graft vs. host disease (GVHD) was not influenced in our cases by
      DC1/DC2 graft composition, but patients with acute GVHD when compared with
      patients without acute GVHD presented a significantly less rapid DC recovery (DC1
      P = 0.03, DC2 P = 0.009 on day +30, and DC1 P = 0.012, DC2 P = 0.006 on day
      +100). At the moment of relapse, a decrease of DC1/DC2 numbers was observed in
      four patients and the presence of two different DC populations one with a normal
      karyotype, and the other with the same cytogenetic abnormality as the malignant
      clone was detected by fluorescence in situ hybridization analysis. In conclusion,
      these observations suggest that in allogeneic HSCT recipients, DC recovery is a
      slow process possibly contributing to the high risk of infections in the post
      transplant period and is possibly influenced by the source of HSC, the occurrence
      of GVHD and relapse. Further studies are warranted to investigate the
      significance of DC reconstitution in the transplant setting.

PMID- 14962259
TI  - Long-term follow up of patients with multiple myeloma after high-dose
      chemotherapy and allogeneic stem cell transplantation.
AB  - OBJECTIVES: Allogeneic transplantation may offer a curative approach to multiple
      myeloma (MM). We retrospectively analyzed the outcome of patients with multiple
      myeloma undergoing allogeneic stem cell transplantation in the context of beta(2)
      microglobulin and chromosome 13q. METHODS: All 13 patients with MM, who were
      referred to our center for allogeneic stem cell transplantation, were evaluated.
      Median age of patients was 38 yr, eight patients had chemo-sensitive disease, and
      median time between diagnosis of MM and transplantation was 15 months.
      Engraftment, acute and chronic graft vs. host disease, response to treatment,
      disease-free survival, and overall survival were evaluated according to standard
      criteria. RESULTS: There was one transplant-related death. Among 12 evaluable
      patients, seven patients (58%) achieved a complete remission (CR), and four
      patients (33%) achieved a partial remission. Acute graft vs. host disease
      occurred in 46% of patients, and chronic graft vs. host disease in 42% of
      available patients. After a median follow-up of 69.5 months (range, 5-128) nine
      patients (70%) are still alive, and six of them have remained progression free.
      Among five patients with low beta(2) microglobulin and normal chromosome 13q,
      four patients achieved a CR, with CR duration >5 yr in three of them. Among seven
      patients with elevated ss(2) microglobulin and/or deletion of chromosome 13q,
      only three CR were observed, with two patients still in CR on days +920 and +161,
      respectively. CONCLUSIONS: Allogeneic stem cell transplantation in patients with
      MM results in promising rates of CR, but durable remissions are predominantly
      seen in patients with favorable prognostic parameters.

PMID- 14962260
TI  - A comparison of fluorine-18 fluoro-deoxyglucose PET and technetium-99m sestamibi
      in assessing patients with multiple myeloma.
AB  - OBJECTIVE: The extent of disease in patients with multiple myeloma or related
      conditions may be difficult to assess. In previous small studies, both FDG-PET
      (PET) and Tc-99m sestamibi scans (MIBI) have identified sites of occult disease
      in myeloma. METHODS: We reviewed the results for patients at our institution who
      have undergone PET and/or MIBI scans to assess myeloma. Concordance between the
      scans, ability to identify otherwise occult disease and impact on patient
      management was assessed. RESULTS: Thirty-six patients had > or =1 PET scan, 56
      had > or =1 MIBI scan and 23 had concurrent PET and MIBI scans. MIBI detected
      additional sites to skeletal survey in 38 of 56 (68%) cases. PET detected
      additional sites to skeletal survey in 18 of 36 (50%) cases. MIBI generally
      detected more disease sites than PET. PET and MIBI were concordant in eight of 23
      (35%) cases. The percentage plasma cell infiltrate within the marrow correlated
      with the number of sites detected by MIBI, but not by PET. In 23 of 69 cases
      (33%), scan results impacted on management, particularly by upstaging disease at
      diagnosis and by recognising subsequent disease progression. The results were
      also helpful for evaluating the presence of ongoing disease activity in
      previously irradiated sites remaining abnormal on skeletal survey following
      treatment. CONCLUSIONS: MIBI and PET are useful additional diagnostic tools for
      detecting otherwise occult sites of myeloma. The use of MIBI PET should
      particularly be considered in the evaluation of a patient with an early-stage
      plasma cell dyscrasia to exclude the presence of more extensive disease.

PMID- 14962261
TI  - Oral treatment of acute myeloid leukaemia with etoposide, thioguanine, and
      idarubicin (ETI) in elderly patients: a prospective randomised comparison with
      intravenous cytarabine, idarubicin, and thioguanine in the second and third
      treatment cycle.
AB  - A randomised multicentre study was conducted among patients over 65 yr of age
      with newly diagnosed acute myeloid leukaemia (AML) to compare oral treatment with
      etoposide 80 mg/m(2) and thioguanine 100 mg/m(2) twice daily on 5 d and
      idarubicin 15 mg/m(2) on 3 d (ETI) to a mainly i.v. combination of cytarabine 100
      mg/m(2) twice daily on 5 d, idarubicin 12 mg/m(2) x 1, and thioguanine (TAI).
      Ninety-two patients were enrolled. Their median age was 72 yr, range 65-84 yr.
      Sixty-five patients had de novo AML, 21 AML subsequent to myelodysplastic
      syndrome, and six treatment-related AML. They received at first a 6-d i.v.
      treatment with cytarabine and idarubicin. After the first treatment, 68 patients
      were randomised to receive two cycles of ETI (n = 36) or TAI (n = 32) and
      thereafter maintenance with mercaptopurine and methotrexate. Of the 92 patients,
      52 (57%) achieved remission at some stage. The median survival was 10 months.
      There were no significant differences between the patients randomised to ETI or
      TAI in the remission rate (67% vs. 72%), survival (12 months from randomisation
      in both arms), event-free survival or relapse rate. The patients randomised to
      receive ETI spent significantly fewer days at hospital during the two randomised
      cycles (20 vs. 41 d, P = 0.010), and they had fewer days with infusions, shorter
      neutropenias and thrombocytopenias and fewer and less severe infections. In
      conclusion, treatment with oral ETI resulted in a similar antileukaemic effect as
      obtained with mainly i.v. TAI, with less toxicity and reduced need for
      hospitalisation.

PMID- 14962262
TI  - Significant co-expression of WT1 and MDR1 genes in acute myeloid leukemia
      patients at diagnosis.
AB  - A high expression of Wilms' tumor gene (WT1) in acute myeloid leukemia (AML)
      seems to correlate with a poor outcome and its increased levels can be predictive
      of an impending relapse. WT1 has been shown in vitro to interact with the
      promoter of the MDR1, a gene involved in the multidrug resistance phenomenon. The
      aim of this study was to measure, by real-time polymerase chain reaction, levels
      of WT1 and MDR1 expression, in order to find a possible association between these
      genes, in a series of 50 newly diagnosed AML cases. Twenty-five percent of
      patients carried very high (>75 degrees percentile) MDR1- and 23.3%WT1-mRNA
      levels. Interestingly, high levels of WT1 were significantly correlated with
      correspondent high levels of MDR1 gene. Nevertheless, the co-expression of these
      genes did not significantly influence the complete response rate to the induction
      therapy. Reported data confirm the existence of a co-expression of WT1 and MDR1
      genes even in vivo; this may be relevant because one consequence could be the
      positive selection by chemotherapeutic regimens of cells with higher MDR1 levels
      already present before treatment. Thus, the association between these genes could
      suggest avoiding the use of drugs involved in the multidrug resistance (MDR)
      phenomenon in patients carrying high levels of WT1 at diagnosis.

PMID- 14962263
TI  - Thalidomide for the treatment of idiopathic myelofibrosis.
AB  - Except rare instances of allogeneic stem cell transplantation, treatment of
      idiopathic myelofibrosis (IMF) is only palliative and based on cytostatic
      treatment (hydroxyurea and anagrelide), androgen therapy, steroids and
      splenectomy. Thalidomide is an anti-angiogenic and immunomodulatory drug with a
      wide spectrum of activities, which are not clearly understood. Current data
      suggest that the action of thalidomide is related to several different
      mechanisms, including suppression of tumor necrosis factor, effects on basic
      fibroblast growth factor, vascular endothelial growth factor, interleukins and
      interferons, downregulation of selected cell surface adhesion molecules, and
      changes in the lymphocyte subsets. We administered thalidomide to 16 patients
      with IMF (15 men, one women) who had transfusion-dependent anemia,
      thrombocytopenia or symptomatic splenomegaly. Median age was 59 yr (range: 52
      78). Patients received thalidomide at an escalating dose from 100 to 400 mg/d
      (median 300 mg). The drug was discontinued in four patients because of
      progressive disease (two) or polyneuropathy (two). Other adverse effects were
      obstipation (10), fatigue (eight) and edema (two). Clinical response has now been
      observed for a median duration of 9 months (range: 3-20). Fifteen patients are
      evaluable. Anemia improved in six of 10 patients who were anemic. Platelet counts
      improved in five of seven patients with thrombocytopenia. Splenomegaly regressed
      in three of 13 patients. Lactate dehydrogenase (LDH) decreased in seven of 12
      patients, but increased in four patients. LDH levels were not correlated with
      clinical response. In summary, thalidomide appears useful in the treatment of
      IMF.

PMID- 14962264
TI  - Ida-FLAG plus imatinib mesylate-induced molecular remission in a patient with
      chemoresistant Ph1+ acute myeloid leukemia.
AB  - Imatinib mesylate is a potent, selective inhibitor of the tyrosine kinase
      activity of bcr-abl,which is now established as the state-of-the-art treatment
      for chronic, accelerated or even blastic phase of Philadelphia-positive
      [Ph(1)(+)] chronic myelogenous leukemia. It is also active in Ph(1)(+) acute
      lymphoblastic leukemia, but its role in Ph(1)(+) acute myeloid leukemia (AML) is
      less well investigated. We report here a patient with chemoresistant Ph(1)(+)
      AML, who responded promptly to one cycle of Ida-FLAG second-line chemotherapy by
      achieving complete morphologic, immunophenotypic, and cytogenetic remission but
      not a molecular one. The addition of imatinib mesylate led to a molecular
      remission, which is sustained for 10 months so far.

PMID- 14962265
TI  - Successful treatment of chemotherapy-refractory Sezary syndrome with alemtuzumab
      (Campath-1H).
AB  - INTRODUCTION: Sezary syndrome (SS) is a cutaneous T-cell lymphoma characterized
      by erythroderma, lymphadenopathy and circulating atypical T cells. Median
      survival after diagnosis is 10 yr, with chemotherapy resistance being a major
      problem in advanced disease. Alemtuzumab (Campath-1H) is a monoclonal antibody
      directed against the lymphocytic antigen CD52, expressed on B- and T-cells.
      Alemtuzumab is approved for relapsing chronic B-cell leukemia and seems to be
      active also in T-cell lymphomas such as T-cell prolymphocytic lymphoma, SS and
      mycosis fungiodes. CASE HISTORY: A 32-yr-old male patient presented with advanced
      stage, extensively pretreated SS with heavily itching erythroderma, peripheral
      lymphadenopathy, circulating Sezary cells and bone marrow infiltration. The
      disease had not responded to PUVA/interferon-alpha and progressed on chemotherapy
      with CHOP, 2-CDA, vinorelbine, etoposide and liposomal doxorubicin. Following
      treatment with alemtuzumab (30 mg i.v. three times per week for 10 wk), itching
      resolved rapidly and an almost complete remission was achieved within 3 months
      after starting this treatment. At 12-month follow up, no disease progression was
      present. CONCLUSION: In accordance with previous data, this single case
      underlines the potent activity of alemtuzumab in advanced, chemotherapy
      refractory SS.

PMID- 14962266
TI  - Treatment of refractory chronic lymphocytic leukemia with Campath-1H in
      combination with lamivudine in chronic hepatitis B infection.
AB  - Campath-1H, a monoclonal antibody against human CD52, is used for the therapy of
      refractory or relapsed chronic lymphocytic leukemia (CLL). Treatment with campath
      is associated with an increased incidence of infections and also fatal
      reactivation of viral infections. Reactivation of hepatitis B virus (HBV) in
      HBsAg-positive patients is a well-documented complication of cytotoxic or
      immunosuppressive therapy and has also been observed after treatment with
      rituximab. To date, there are no reports on campath treatment in HBsAg carriers.
      Here, we present the case of a patient with heavily pretreated CLL who was HBsAg
      positive with a high virus load (>2 billion copies/mL). He required treatment
      because of progressive CLL with massive bone marrow infiltration, severe anemia
      and thrombocytopenia. Campath was initiated and lamivudine, an inhibitor of
      reverse transcriptase, was simultaneously given to prevent HBV proliferation.
      During the treatment, no deterioration of liver parameters was observed, and the
      virus load decreased. After therapy with campath, hemoglobin and platelet counts
      increased markedly. This report shows that lamivudine is highly effective in
      inhibiting HBV proliferation and can be used to prevent HBV flare-up during
      campath treatment in patients tested positive for HBs antigen.

PMID- 14962267
TI  - Severe central nervous system thrombotic events in hemoglobin Sabine patient.
AB  - Hemoglobin (Hb) Sabine is a rare, unstable Hb variant resulting from the point
      mutation in codon 91 (CTG --> CCG) of beta-globin gene. We report a case of Hb
      Sabine patient with mild hemolytic anemia, unusually high Hb F level and severe
      central nervous system thrombotic disturbances. We have tried to elucidate
      possible genetic background of this unusual Hb Sabine phenotype. Extremely high
      level of Hb F and rather mild anemia in our patient could be partially explained
      by the presence of G gamma Xmn I polymorphism. This case of Hb Sabine, unlike all
      other reported to date, shows extremely severe thromboembolic complications. It
      is our opinion that the hypercoagulable state described in thalassemia is not the
      only factor responsible for this specific clinical state. The presence of MTHFR
      C677T mutation in heterozygous state found in our patient and unstable Hb Sabine
      molecules could contribute to development of thromboembolic phenomena. However,
      it remains unclear whether other factors participate in pathogenesis of the
      disease. In this paper we emphasize different genetic background of father and
      son both affected with Hb Sabine, but with markedly different severity of the
      disease.

PMID- 14962268
TI  - Myocardial ischemia in a patient with acute lymphoblastic leukemia during L
      asparaginase therapy.
AB  - Haemostatic abnormalities may occur in 1-2% of patients treated with L
      asparaginase. Here, we present the second case of a myocardial infarction,
      developing in a patient with acute lymphoblastic leukemia (ALL), in the course of
      L-asparaginase treatment. In our patient and in the only one reported case from
      the literature, a recent exposure to vincristine and daunorubicin was also
      reported, but induction chemotherapy program was completed as scheduled, with the
      only withdrawal of L-asparaginase. Myocardial infarction should be included in
      the list of thrombotic complications possibly associated with L-asparaginase
      treatment, or with a combination of L-asparaginase and vinca
      alkaloids/anthracycline.

PMID- 14962269
TI  - A case of a long-time survivor with chronic active Epstein-Barr virus infection.
AB  - Epstein-Barr virus (EBV) is associated with hypersensitivity to mosquito bites
      (HMB) and fatal EBV-associated hemophagocytic syndrome (HPS). The prognosis of
      patients with chronic active EBV infection (CAEBV) is very poor. We report a rare
      case of an adult woman patient with a 28-yr history of HMB, who developed EBV
      HPS. EBV genome was detected in the serum and peripheral blood lymphocytes.
      Clonal proliferation of EBV was demonstrated by Southern blot analysis using an
      EBV genome terminal-repeat probe. This is a very rare case of a long-term
      survivor with CAEBV. The patient was initially treated with immunochemotherapy
      and achieved complete remission. However, the patient immediately relapsed and
      underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched
      brother. Peripheral blood cell recovered well, and EBV genome disappeared from
      the peripheral blood. Allogeneic BMT may be effective in eradicating EBV-HPS.
      Unfortunately, the patient died of graft vs. host disease on the 92nd day after
      BMT.

PMID- 14962273
TI  - The study of mitoxantrone as a potential immunosuppressor in transgenic pig renal
      xenotransplantation in baboons: comparison with cyclophosphamide.
AB  - Mounting evidence suggests that delayed xenograft rejection (DXR) of discordant
      xenografts has a strong humoral component. To explore the possibility of
      targeting this humoral response more efficiently, we performed a preliminary
      study in baboons immunized against pig blood cells using the immunosuppressor
      mitoxantrone (Mx). The results from this study showed that, in comparison with
      cyclophosphamide (CyP), Mx induced a long-lasting depletion of circulating B
      cells within 6 days of its administration and delayed secondary anti-Gal antibody
      (Ab) responses to pig blood cell immunizations. Given these results, we next
      evaluated Mx in an in vivo model of pig to baboon renal xenotransplantation. We
      performed a series of renal xenotransplantations in baboons using human CD55-CD59
      transgenic donor pigs. In the first group of baboons (Mx group; n = 4) Mx was
      administered 6 days prior to the day of transplantation, the objective being to
      perform the xenotransplantation in a context where the recipient would have few
      remaining circulating B cells and thus have an impaired capacity to mount an Ab
      response to the xenograft. We compared this group to a second group of baboons
      treated with CyP starting 1 day prior to transplantation (CyP group; n = 2). All
      baboons receiving Mx or CyP received an additional immunosuppression of
      cyclosporin A, mycophenolate mofetil and steroids. No hyperacute rejection was
      observed in either group but all xenografts underwent DXR. Mx did not show
      superiority to CyP in terms of graft survival with a mean survival time of 8 +/-
      2 days compared with 9 days for both CyP-treated baboons. Neither CyP nor Mx
      decreased serum levels of pre-existing anti-Gal Abs but levels of these Abs
      decreased dramatically within 1 day of transplantation, likely reflecting their
      immediate trapping within the xenograft. Interestingly however, in contrast to
      CyP, Mx inhibited the return of anti-Gal immunoglobulin M (IgM) to the
      circulation, even at the time of rejection. Nevertheless, strong intragraft
      deposits of IgM, IgG and the activated complement complex C5b-9 were observed in
      biopsies at rejection. Furthermore, despite the expected profound depletion of
      circulating B cells by Mx within 6 days of its administration, biopsies from both
      groups at rejection displayed a mild B cell infiltrate accompanied by a strong
      macrophage and intermediate T-cell infiltration, the latter tending to be more
      abundant in Mx-treated animals. Our data show that in this particular model of
      pig to baboon xenotransplantation and at the dose used, Mx was not superior to
      CyP in conferring protection against rejection, despite its capacity to
      profoundly deplete circulating B cells and to inhibit anti-Gal Ab responses to
      xenografts. DXR was thus possible without the return of anti-Gal Abs and may have
      been mediated by the early fixation of pre-existing Abs with secondary complement
      activation. However, although Mx was not more efficient than CyP in controlling
      DXR, its capacity to deplete B cells and delay Ab recovery may be beneficial in
      the context of Gal knockout organ transplantation where the induced Ab response
      is likely to take precedence over the preformed response.

PMID- 14962274
TI  - Improved suppression of circulating complement does not block acute vascular
      rejection of pig-to-rhesus monkey cardiac transplants.
AB  - At present, acute vascular rejection (AVR) remains a primary obstacle inhibiting
      long-term graft survival in the pig-to-non-human primate transplant model. The
      present study was undertaken to determine whether repetitive injection of low
      dose Yunnan-cobra venom factor (Y-CVF), a potent complement inhibitor derived
      from the venom of Naja kaouthia can completely abrogate hemolytic complement
      activity and subsequently improve the results in a pig-to-rhesus monkey
      heterotopic heart transplant model. Nine adult rhesus monkeys received a
      heterotopic heart transplant from wild-type pigs and the recipients were
      allocated into two groups: group 1 (n = 4) received repetitive injection of low
      dose Y-CVF until the end of the study and group 2 (n = 5) did not receive Y-CVF.
      All recipients were treated with cyclosporine A (CsA), cyclophosphamide (CyP) and
      steroids. Repetitive Y-CVF treatment led to very dramatic fall in CH50 and serum
      C3 levels (CH50 < 3 units/C3 remained undetectable throughout the experiment) and
      successfully prevented hyperacute rejection (HAR), while three of five animals in
      group 2 underwent HAR. However, the continuous suppression of circulating
      complement did not prevent AVR and the grafts in group 1 survived from 8 to 13
      days. Despite undetectable C3 in circulating blood, C3 deposition was present in
      these grafts. The venular thrombosis was the predominant histopathologic feature
      of AVR. We conclude that repetitive injection of low dose Y-CVF can be used to
      continuously suppress circulating complement in a very potent manner and
      successfully prevent HAR. However, this therapy did not inhibit complement
      deposition in the graft and failed to prevent AVR. These data suggest that using
      alternative pig donors [i.e. human decay accelerating factor (hDAF)-transgenic]
      in combination with the systemic use of complement inhibitors may be necessary to
      further control complement activation and improve survival in pig-to-non-human
      primate xenotransplant model.

PMID- 14962275
TI  - Understanding of and attitudes to xenotransplantation: a survey among Italian
      university students.
AB  - Xenotransplantation is currently at the experimental stages on animal models and
      many problems still have to be overcome in the biomedical, immunological and
      ethical fields. Moreover, people's attitudes to xenotransplantation vary: surveys
      among intensive-care staff have revealed negative opinions, while the general
      public and students seem to be more positive. Little is known about the influence
      of schooling and the choice of university faculty on attitudes to
      xenotransplantation. The aims of this study were: (i) to evaluate university
      students' attitudes to xenotransplantation; (ii) to investigate any socio
      demographic, religious and educational determinants behind students' opinions on
      xenotransplantation. University undergraduates on five different courses were
      surveyed at Padua University. A 24-item questionnaire was distributed to students
      at the end of lectures and completed anonymously immediately after its
      distribution. No information was given to students beforehand. STATISTICAL
      ANALYSIS: chi-squared, Pearson's test; P-values <0.05 were considered
      significant. A total of 585 of 602 (97.2%) students completed the questionnaire
      (132 males, 453 females, mean age 20.4, range 19 to 43 yr). They were on courses
      in Medicine (33.85%), Agriculture (5.98%), Veterinary Medicine (11.45%),
      Psychology (18.46%) and Educational Sciences (30.26%). As for their previous
      schooling, they came from classical or scientific high school (58.3%), technical
      college (14.7%), language college (6.3%), teacher training college (11.9%) or
      others (8.8%). Concerning their religious beliefs, 83% were Catholics, and 56.2%
      defined themselves as practising Catholics. Eighty-eight percentage of the
      students knew of the possibility of animal organs being transplanted into humans
      and 77.9% of them approved of this idea. When grouped according to gender and
      education, a higher proportion of students approving of xenotransplantation were
      male (P = 0.017) and had attended classical or scientific high school (P =
      0.011). Disapproval for moral, ethical or religious reasons was higher among
      practising than among non-practising Catholics; the latter rejected
      xenotransplantation more for immunological and infectious reasons (P = 0.014). As
      for the type of university course, a higher proportion of students approving of
      xenotransplantation attended science courses (Veterinary Medicine, Agriculture
      and Medicine vs. Educational Sciences and Psychology) (P = 0.013). University
      students generally approved of xenotransplantation. Male gender and a high-school
      education were associated with a greater acceptance of xenotransplantation.
      Practising vs. non-practising Catholics reported significantly different reasons
      for any disapproval of xenotransplantation. The choice of a science rather than
      an arts faculty at university was more strongly associated with a positive
      opinion on xenotransplantation.

PMID- 14962276
TI  - Immunoglobulin M-enriched intravenous immunoglobulin inhibits classical pathway
      complement activation, but not bactericidal activity of human serum.
AB  - Acute or even hyperacute humoral graft rejection, mediated by classical pathway
      complement activation, occurs in allo- and xenotransplantation due to preformed
      anti-graft antibodies. Intravenous immunoglobulin (IVIg) preparations can prevent
      complement-mediated tissue injury and delay hyperacute xenograft rejection. It is
      known that IgM-enriched IVIg (IVIgM) has a higher capacity to block complement
      than IVIgG. Different IVIgs were therefore tested for specificity of complement
      inhibition and effect on anti-bacterial activity of human serum. IVIgM-I
      (Pentaglobin), 12% IgM), IVIgM-II (IgM-fraction of IVIgM-I, 60% IgM), and three
      different IVIgG (all >95% IgG) were used. The known complement inhibitor dextran
      sulfate was used as control. Hemolytic assays were performed to analyze pathway
      specificity of complement inhibition. Effects of IVIg on complement deposition on
      pig cells and Escherichia coli were assessed by flow cytometry and cytotoxicity
      as well as bactericidal assays. Complement inhibition by IVIgM was specific for
      the classical pathway, with IC50 values of 0.8 mg/ml for IVIgM-II and 1.7 mg/ml
      for IVIgM-I in the CH50 assay. Only minimal inhibition of the lectin pathway was
      seen with IVIgM-II (IC50 15.5 mg/ml); no alternative pathway inhibition was
      observed. IVIgG did not inhibit complement in any hemolytic assay. Classical
      pathway complement inhibition by IVIgM was confirmed in an in vitro
      xenotransplantation model with PK15 cells. In contrast, IVIgM did not inhibit
      (mainly alternative pathway mediated) killing of E. coli by human serum. In
      conclusion, IgM-enriched IVIg is a specific inhibitor of the classical complement
      pathway, leaving the alternative pathway intact, which is an important natural
      anti-bacterial defense, especially for immunosuppressed patients.

PMID- 14962277
TI  - Histological and immunological characteristics of, and the effect of
      immunosuppressive treatment on, xenograft vasculopathy.
AB  - Like allografts, vascularized xenografts are susceptible to a process of chronic
      rejection. We have used the hamster-to-rat aortic transplant model to study
      characteristics of this phenomenon and to determine whether it could be
      controlled or prevented by immunosuppressive therapy. Golden Syrian hamster
      aortas were transplanted into untreated Lewis rats, athymic rats, and Lewis rats
      receiving cyclosporin (10 mg/kg), leflunomide (5, 10 or 15 mg/kg), or 10 mg/kg of
      both drugs. Grafts were harvested on days 2, 7, 14, 28 and 56. Grafts and
      recipient spleens were analysed using computerized morphometry,
      immunohistochemistry and immunofluorescence. Blood was taken on various days for
      the measurement of anti-hamster antibodies (flow cytometry) and of the
      leflunomide metabolite A77 127. In untreated rats, by day 56, transplanted aortas
      developed a cell-free media with a mature neointimal lesion consisting of actin
      positive cells, CD4 T cells, and macrophages. There were large increases in anti
      hamster immunoglobulin M (IgM) and IgG, collections of proliferating cell nuclear
      antigen (PCNA)-positive cells in splenic germinal centres, and IgM, C3 and C5a
      deposition in aortas. In athymic recipients, the media architecture was
      preserved, and the changes in the neointima and in anti-hamster IgM and IgG were
      markedly abrogated, but not prevented. In Lewis rats receiving leflunomide,
      absence of circulating or deposited IgM did not prevent neointimal formation by
      day 14. Combination treatment was the most effective at preventing neointimal
      formation and humoral changes. Leflunomide monotherapy was the least effective.
      There were no changes in peak concentrations of the main metabolite of
      leflunomide over 8 weeks. The hamster-to-rat aortic transplant model is suitable
      for the study of xenograft vasculopathy, the histological and serological changes
      of which are predominantly T-cell dependent. Combination treatment with 10 mg/kg
      of cyclosporin and 10 mg/kg of leflunomide was most effective in preventing
      xenograft vasculopathy.

PMID- 14962278
TI  - Transplanting encephalomyocarditis virus-infected porcine islet cells reverses
      diabetes in recipient mice but also transmits the virus.
AB  - Previous studies demonstrated that porcine encephalomyocarditis virus (EMCV)
      caused acute and persistent infection in the myocardium, central nervous system,
      and spleen of non-human primates (cynomolgus macaques); and it productively
      infected primary human cardiomyocytes, suggesting that the virus may pose a risk
      in pig-to-human transplantation. Recently, transplantation of myocardial and
      pancreatic tissues from acutely infected pigs transmitted the virus to recipient
      mice, resulting in acute fatal EMCV disease. Here, we examined whether porcine
      islet cells (PICs), which are under clinical trial for treatment of type I
      diabetes in humans, are susceptible to porcine EMCV, and whether EMCV-infected
      PICs could function in vivo to reverse diabetes. PICs were infected with EMCV in
      vitro for 5 h, and resulting insulin production compared with that produced by
      uninfected PICs. Subsequently, infected PICs were transplanted intra-abdominally
      or under the kidney capsule of C57BL/6 mice, and both virus transmission and PIC
      function analyzed. PICs were highly susceptible to porcine EMCV, resulting in a
      1500-fold increase in production of infectious virus within 5 h of inoculation
      and cytolysis that destroyed up to 50% of cells within 96 h. However, as long as
      they were viable, infected PICs produced insulin at levels comparable with
      uninfected PICs. Intra-abdominal transplantation of 2000 PICs, infected with one
      plaque forming unit (pfu) per cell of porcine EMCV, into C57BL/6 mice transmitted
      the virus resulting in acute fatal EMCV disease characterized by hind limb
      paresis and paralysis and acute respiratory distress in 40% of recipient mice.
      More importantly, transplantation of 2500 EMCV-infected PICs under the kidney
      capsule of diabetic C57BL/6 mice (glucose level > or =350 mg/dl) reversed
      diabetes in 83% of recipient mice (glucose level < or =170 mg/dl); however these
      mice succumbed to acute EMCV disease transmitted by the xenograft 5 days after
      transplantation. EMCV infection does not appear to affect insulin production by
      PICs, but infected xenografts can transmit the virus to recipient animals,
      resulting in severe disease.

PMID- 14962279
TI  - Characterization of a CD46 transgenic pig and protection of transgenic kidneys
      against hyperacute rejection in non-immunosuppressed baboons.
AB  - Human membrane cofactor protein (CD46) controls complement activation and when
      expressed sufficiently as a transgene protects xenografts against complement
      mediated rejection, as shown here using non-immunosuppressed baboons and
      heterotopic CD46 transgenic pig kidney xenografts. This report is of a carefully
      engineered transgene that enables high-level CD46 expression. A novel CD46
      minigene was validated by transfection and production of a transgenic pig line.
      Pig lymphocytes were tested for resistance to antibody and complement-mediated
      lysis, transgenic tissues were characterized for CD46 expression, and kidneys
      were transplanted to baboons without immunosuppression. Absorption of anti
      Galalpha(1,3)Gal epitope (anti-GAL) serum antibodies was measured. Transgenic
      pigs expressed high levels of CD46 in all tissues, especially vascular
      endothelium, with stable expression through three generations that was readily
      monitored by flow cytometry of transgenic peripheral blood mononuclear cells
      (PBMC). Transgenic PBMC pre-sensitized with antibody were highly resistant to
      human complement-mediated lysis which readily lysed normal pig PBMC. Normal pig
      kidneys transplanted without cold ischemia into non-immunosuppressed adult
      baboons survived a median of 3.5 h (n = 7) whereas transgenic grafts (n = 9),
      harvested at approximately 24-h intervals, were either macroscopically normal (at
      29, 48 and 68 h) or showed limited macroscopic damage (median > 50 h).
      Microscopic assessment of transplanted transgenic kidneys showed only focal
      tubular infarcts with viable renal tissue elsewhere, no endothelial swelling or
      polymorph adherence and infiltration by lymphocytes beginning at 3 days.
      Coagulopathy was not a feature of the histology in four kidneys not rejected and
      assessed at 48 h or later after transplantation. Baboon anti-GAL serum antibody
      titers were high before transplantation and, in one extensively analyzed
      recipient, reduced approximately 8-fold within 5.5 h. The data demonstrate that a
      single CD46 transgene controls hyperacute kidney graft rejection in untreated
      baboons despite the presence of antibody and complement deposition. The
      expression levels, tissue distribution and in vitro functional tests indicate
      highly efficient CD46 function, controlling both classical and alternative
      pathway complement activation, which suggests it might be the complement
      regulator of choice to protect xenografts.

PMID- 14962280
TI  - Adult porcine islets produce MCP-1 and recruit human monocytes in vitro.
AB  - Type 1 diabetes can be cured by transplantation of isolated pancreatic islets.
      Because of the shortage of human donor tissue, adult porcine islets (APIs)
      constitute a possible alternative tissue source. Upon intraportal injection,
      islets are subjected to an instant blood-mediated inflammatory reaction (IBMIR)
      leading to blood clotting, leukocyte islet-infiltration, islet damage and insulin
      release. Xenogeneic islets surviving IBMIR are rejected in a cellular process
      involving CD4(+) T lymphocytes and macrophages. We have investigated whether APIs
      themselves produce and secrete chemokines and/or inflammatory cytokines that may
      contribute to IBMIR and/or cell-mediated rejection. APIs, cultured for 1, 4, 8
      and 11 days post-isolation, expressed mRNA for monocyte chemoattractant protein-1
      (MCP-1), IL-1beta and TNF-alpha. API culture supernatants induced migration of
      human monocytes, which was significantly blocked by an anti-human MCP-1 antibody
      (Ab). Immunohistochemistry revealed MCP-1 in the cytoplasm of alpha- and beta
      cells in isolated islets and in islets in situ. However, APIs or their
      supernatants were not able to activate human aortic endothelial cells (HAECs) in
      vitro, and neither IL-1beta nor TNF-alpha were detected by enzyme-linked
      immunosorbent assay (ELISA) in API culture supernatants. Both recombinant porcine
      IL-1beta and TNF-alpha were able to activate human endothelial cells (ECs)
      inducing CD62E and CD106 expression as analyzed by flow cytometry. In conclusion,
      MCP-1 secreted by APIs may contribute to both IBMIR and rejection by attracting
      monocytes into the islet; monocytes which upon transformation into macrophages
      will potentiate antigen presentation and execute islet rejection.

PMID- 14962281
TI  - Intraportal pig islet xenotransplantation into athymic mice as an in vivo model
      for the study of the instant blood-mediated inflammatory reaction.
AB  - One of the main obstacles to successful intraportal islet transplantation is the
      instant blood-mediated inflammatory reaction (IBMIR) elicited by the isolated
      islets when exposed to fresh human blood. In the present study, we investigated
      whether intraportal transplantation of pig islets into diabetic athymic mice
      could be used as a small animal model to study xenogeneic IBMIR in vivo. Adult
      porcine islets (APIs) or rat islets were implanted into the portal vein or under
      the renal subcapsular space of diabetic athymic mice. Graft survival and
      morphology were evaluated by measuring blood glucose levels and by performing
      immunohistochemical staining, respectively. Transplantation of rat islets,
      irrespective of implantation site, cured all diabetic athymic mice. APIs
      transplanted subcapsularly also cured all diabetic athymic mice, while none of
      the animals transplanted with an equivalent amount of APIs via the portal vein
      remained normoglycemic for more than 10 days after transplantation.
      Immunohistochemical staining on day 7 showed that most of intraportally
      transplanted APIs were entrapped in clots and infiltrated with CD11b+ leukocytes.
      Intraportal transplantation of APIs into athymic mice induced IBMIR, thus
      providing a small animal model for studying xenogeneic IBMIR.

PMID- 14962282
TI  - TMVA, a novel GPIb-binding protein, significantly prevents platelet microthrombi
      formation and prolongs discordant cardiac xenograft survival.
AB  - In xenotransplantation, donor endothelium is the first target of immunological
      attack. Activation of the endothelial cell by preformed natural antibodies leads
      to platelet binding via the interaction of the glycoprotein (GP) Ib and von
      Willebrand factor (vWF). TMVA is a novel GPIb-binding protein purified from the
      venom of Trimeresurus mucrosquamatus. In this study, the inhibitory effect of
      TMVA on platelet aggregation in rats and the effect on discordant guinea pig-to
      rat cardiac xenograft survival were investigated. Three doses (8, 20 or 40
      microg/kg) of TMVA were infused intravenously to 30 rats respectively. Platelet
      aggregation rate was assayed 0.5, 12, and 24 h after TMVA administration. Wister
      rats underwent guinea pig cardiac cervical heterotopic transplantation using
      single dosing of TMVA (20 microg/kg, i.v., 0.5 h before reperfusion).
      Additionally, levels of TXB(2) and 6-keto-PGF(1alpha) within rejected graft
      tissues were determined by radioimmunoassay. Treatment with TMVA at a dose of 20
      or 40 microg/kg resulted in complete inhibition of platelet aggregation 0.5 h
      after TMVA administration. Rats receiving guinea pig cardiac xenografts after
      TMVA therapy had significantly prolonged xenograft survival. Histologic and
      immunopathologic analysis of cardiac xenografts in TMVA treatment group showed no
      intragraft platelet microthrombi formation and fibrin deposition. Additionally,
      the ratio of 6-keto-PGF(1alpha) to TXB(2) in TMVA treatment group was
      significantly higher than those in control group. We conclude that the use of
      this novel GPIb-binding protein was very effective in preventing platelet
      microthrombi formation and fibrin deposition in a guinea pig-to-rat model and
      resulted in prolongation of xenograft survival. The increased ratio of
      PGI(2)/TXA(2) in TMVA treatment group may protect xenografts from the endothelial
      cell activation and contribute to the prolongation of xenograft survival.

PMID- 14962283
TI  - Reduction of anti-Galalpha1,3Gal antibodies by infusion of types 2 and 6 gal
      trisaccharides conjugated to poly-L-lysine.
AB  - To investigate the specificity of anti-Galalpha1,3Gal (Gal) antibodies (Abs) with
      respect to Gal oligosaccharides of types 2 and 6, eight baboons received an
      intravenous infusion of either a poly-l-lysine conjugate of Gal type 2 (n = 5) or
      type 6 (n = 3), followed 48 h later by the alternative Gal type 6 or 2 conjugate,
      respectively. IgM Abs reactive to Gal type 2 were depleted by 80 to 89% by either
      Gal conjugate. IgM reactive to Gal type 6 was less efficiently depleted by the
      Gal type 2 conjugate (57% depletion) than the Gal type 6 (82% depletion). Gal
      reactive IgG was depleted more slowly and less efficiently by either
      glycoconjugate (initially by only 28 to 54%). Our results indicate that the Gal
      type 6 conjugate depletes most anti-Gal IgM, but the Gal type 2 conjugate is less
      efficient in depleting anti-Gal IgM reactive with type 6. There remain small
      fractions of antibody that are unadsorbed, particularly of IgG, probably due to
      their low affinity and distribution in both the intra- and extra-vascular
      compartments.

PMID- 14962284
TI  - Xenotransplantation literature update October-December, 2003.

PMID- 14962287
TI  - Xenotransplantation literature update. January-October, 2003.

PMID- 14962288
TI  - In vitro studies regarding the feasibility of bovine erythrocyte xenotransfusion.
AB  - Pigs are considered the most likely source of organs and tissues should the
      barriers to xenotransplantation be overcome. The use of animal blood for
      transfusion, xenotransfusion, would have advantages over blood from random human
      donors with respect to supply and infection control. Large animals such as cows
      would be more suitable than pigs for blood donation because of easier venous
      access and large volume phlebotomy. Blood from 12 Holstein cows was typed and
      then tested for hemagglutination assay (HA), complement mediated lysis (CML),
      human IgM and IgG antibody binding, anti-human globulin augmented clinical cross
      match and osmotic fragility with normal human serum. Results were compared with
      porcine erythrocytes (pRBC) and with human type O controls (hRBC). The frequency
      of ultra-low xenoantigen expressors was tested in a larger herd of various breeds
      using HA and CML. Median HA and CML titers were one of six (no HA-one of 64) and
      one of 26 (no CML-one of 64), respectively for bovine erythrocytes (bRBC).
      Hemagglutination titer was significantly higher for pRBC at one of 170 (one of
      four-one of 1024). HA and CML were lowest with bovine blood group J. Repeated HA
      and CML were negative with bRBC from one cow that also tested negative by anti
      human globulin augmented cross-match with seven of nine random human sera
      representing the different blood groups. However, flow cytometry showed that bRBC
      from all cows bound human IgM and IgG. IgM mean channel fluorescence (MCF) was
      positively correlated with HA titer. The mean corpuscular fragility of pRBC,
      bRBC, and hRBC was 0.56, 0.48 and 0.41%, respectively. The frequency of HA
      negative and CML-negative cows were 20 and 35%, respectively in herds of 49
      animals. Bovine RBC elicit variable in vitro responses from human serum but these
      are uniformly much less than those seen with pRBC. Bovine RBC is more robust than
      pRBC. These characteristics including the potential ease and volume of blood
      collection make the cow a more suitable blood donor than the pig.

PMID- 14962289
TI  - Initial investigation of the potential of modified porcine erythrocytes for
      transfusion in primates.
AB  - There is a shortage of human blood for transfusion. The possibility of using
      alpha-galactosidase-treated pig red blood cells (pRBCs) for transfusion into
      humans has been investigated. pRBCs were treated in vitro with alpha
      galactosidase. In vitro binding of antibodies (Abs) in baboon or human sera to
      untreated/treated pRBCs was assessed by flow cytometry and serum cytotoxicity. In
      vivo clearance rates of (1) autologous baboon red blood cells (RBCs), (2)
      unmodified pRBCs, and (3) alpha-galactosidase-treated pRBCs were measured after
      transfusion into baboons receiving either no treatment or depletion of complement
      +/- depletion of anti-Gal alpha 1-3Gal (Gal) Ab or of macrophage phagocytes. In
      vitro binding of baboon or human Abs to treated pRBCs was absent or minimal
      compared with untreated pRBCs, and serum cytotoxicity was completely inhibited.
      In vivo autologous baboon RBCs survived for >16 days and unmodified pRBCs for <15
      min in an untreated baboon. Treated pRBCs survived for 2 h in an untreated
      baboon, for 24 h in a complement-depleted baboon, and for 72 h when the baboon
      was depleted of both complement and anti-Gal Ab, or of complement and macrophage
      phagocytes. All baboons, however, became sensitized to Gal antigens. Failure to
      prolong the in vivo survival of treated pRBCs could be due to inadequate removal
      of Gal epitopes because sensitization to Gal developed, or could imply other, as
      yet unidentified, causes for RBC destruction. To fully assess the potential of
      pRBC transfusion in humans, more complete alpha-galactosidase treatment of pRBCs
      will be required.

PMID- 14962290
TI  - Absence of humoral and cellular alloreactivity in baboons sensitized to pig
      antigens.
AB  - AIM: to study whether sensitization to pig antigens results in humoral and/or
      cellular sensitization to alloantigens in baboons, and thus increases the risks
      of organ allotransplantation after xenotransplantation. Serum from baboons that
      were naive (n = 4), sensitized to Gal alpha 1,3Gal (Gal) antigens (n = 2), or
      sensitized to Gal + non-Gal pig antigens (n = 2) were tested by flow cytometry
      for the presence of immunoglobulin G (IgG) and IgM antibodies that bind to pig or
      baboon peripheral blood mononuclear cells (PBMC). Two allosensitized baboons were
      used as positive controls. The same 10 sera were tested in a complement-mediated
      cytotoxicity assay to detect cytotoxic antibodies against pig, allo and self
      PBMC. The T-cell responses of the same baboons to allogeneic and pig PBMC
      stimulators in mixed lymphocyte reaction (MLR) were studied. All baboon sera
      contained cytotoxic antibodies that bound to pig PBMC. Binding and cytotoxicity
      were higher in xenosensitized baboons, particularly in those sensitized to Gal +
      non-Gal antigens (P < 0.001). None of the naive or xenosensitized baboon sera
      bound to baboon PBMC. Serum from allosensitized baboons showed anti-baboon IgG
      and IgM binding, but there was no increase in binding to pig PBMC or in
      cytotoxicity to pig cells. The MLR response to pig stimulators in baboons
      sensitized to non-Gal pig antigens was greater than that of naive or Gal
      sensitized baboons (P < 0.001), but there was no increase in the response to
      baboon cells. In baboons, no in vitro evidence that a previous pig xenograft
      might endanger the outcome of a subsequent allograft was documented.

PMID- 14962291
TI  - Blockade of indirect recognition mediated by CD4+ T cells leads to prolonged
      cardiac xenograft survival.
AB  - The T-cell response to xenografts is induced by direct and indirect recognition
      of xenoantigens. Although the importance of indirect recognition is well
      established in vitro, the contribution of this pathway to xenograft rejection in
      vivo remains to be fully elucidated. We herein investigated the direct
      contribution of indirect recognition to cardiac xenograft rejection in the rat-to
      mouse (PVG.R8-to-C57BL/10) concordant model. Rat xenoantigens invoked a vigorous
      proliferative response in mouse T cells harvested from naive or graft recipients
      at rejection. Indirect recognition predominated the response, as antibodies
      against mouse class II I-A(b), CD80, or CD86 molecules significantly (45 to 60%)
      blocked the proliferative response. Importantly, the blockade of indirect
      recognition in vivo by treating the graft recipients with a monoclonal antibody
      (mAb) against class II I-A(b) molecule on days 0, 1, and 3 post-transplantation
      resulted in significant (P < 0.009) prolongation of cardiac xenograft survival
      (Mean Survival Time (MST) >94 +/- 55 days vs. 7 +/- 0.8 days for controls). In
      contrast, treatment of recipients with a mAb against mouse class I H-2K(b)/D(b)
      molecules did not significantly affect graft rejection (MST = 8 +/- 1 days).
      These results demonstrate that indirect recognition mediated by CD4(+) T cells
      plays a critical role in the rejection of cardiac grafts in the rat-to-mouse
      xenogeneic model.

PMID- 14962292
TI  - Human Fas-ligand expression on porcine endothelial cells does not protect against
      xenogeneic natural killer cytotoxicity.
AB  - Several human leukocyte subsets including natural killer (NK) cells, cytotoxic T
      lymphocytes (CTL), and polymorphonuclear neutrophils (PMN) participate in
      cellular immune responses directed against vascularized pig-to-human xenografts.
      As these leukocytes express the death receptor Fas either constitutively (PMN) or
      upon activation (NK, CTL), we explored in vitro whether the transgenic expression
      of Fas ligand (FasL) on porcine endothelial cells (EC) is a valuable strategy to
      protect porcine xenografts. The porcine EC line 2A2 was stably transfected with
      human FasL (2A2-FasL) and interactions of 2A2-FasL with human leukocytes were
      analyzed using functional assays for apoptosis, cytotoxicity, chemotaxis,
      adhesion under shear stress, and transmigration. FasL expressed on porcine EC
      induced apoptosis in human NK and T cells, but did not protect porcine EC against
      killing mediated by human NK cells. 2A2-FasL released soluble FasL, which induced
      strong chemotaxis in human PMN. Adhesion under shear stress of PMN on 2A2-FasL
      cells was increased whereas transendothelial migration was decreased. In
      contrast, FasL had no effect on the adhesion of NK cells but increased their
      transmigration through porcine EC. Although FasL expression on porcine EC is able
      to induce apoptosis in human effector cells, it did not provide protection
      against xenogeneic cytotoxicity. The observed impact of FasL on adhesion and
      transendothelial migration provides evidence for novel biological functions of
      FasL.

PMID- 14962293
TI  - Enhanced expression of glutathione peroxidase protects islet beta cells from
      hypoxia-reoxygenation.
AB  - The survival of pancreatic islet beta-cell xenografts and allografts may be
      affected by damaging reactive oxygen and nitrogen species generated during
      hypoxia-reoxygenation. Peroxynitrite, which is formed from superoxide and nitric
      oxide, appears to be an important mediator of beta-cell destruction. The
      intracellular antioxidant enzymes glutathione peroxidase-1 (Gpx-1) and copper
      zinc superoxide dismutase (CuZn SOD) detoxify peroxynitrite and superoxide,
      respectively. The aim of this study was to examine whether enhanced expression of
      Gpx-1 and/or CuZn SOD protected NIT-1 mouse insulinoma cells from hypoxia
      reoxygenation injury. Stable transfectants expressing human Gpx-1 or CuZn SOD
      were isolated and tested for their resistance to hydrogen peroxide (H(2)O(2)) and
      menadione, which generates superoxide intracellularly. Clones expressing one or
      both enzymes were subjected to hypoxia in glucose-free medium for 18 h, followed
      by reoxygenation in complete medium for 1.5 h. Cell viability was measured using
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) reduction
      assay. Increases of up to two fold in Gpx or total SOD activity protected NIT-1
      cells from H(2)O(2) and menadione. Expression of Gpx-1 significantly increased
      NIT-1 survival following hypoxia-reoxygenation (viability 65 +/- 9% vs. control
      15 +/- 3%, P < 0.001) but CuZn SOD expression had no effect (15 +/- 1%).
      Expression of both enzymes was no more protective (60 +/- 6%) than expression of
      Gpx-1 alone. Genetic manipulation of islet beta cells to increase expression of
      Gpx-1 may protect them from oxidative injury associated with the transplantation
      procedure.

PMID- 14962294
TI  - Complement regulatory proteins are expressed at low levels in embryonic human,
      wild type and transgenic porcine neural tissue.
AB  - Allotransplantation of human foetal neural tissue for neurodegenerative disorders
      has been shown to provide clinical benefit but is limited by a number of issues
      including donor supply. The use of porcine foetal tissue as an alternative source
      of cells is being investigated but xenotransplants survive poorly as a result of
      immunological rejection, which may involve complement. In this study we
      investigated the expression of the membrane-bound complement regulatory proteins-
      decay accelerating factor (DAF), membrane co-factor protein (MCP) and CD59 in
      embryonic neural tissue. Cells were derived from human foetuses, wild-type
      porcine foetuses and porcine foetuses transgenic for human complement regulatory
      proteins and analysed using flow cytometry and immunocytochemistry. Functional
      assessment of human complement regulatory protein expression in transgenic
      porcine tissue was assessed by C3b deposition and cell survival on exposure to
      human complement. Human and wild-type porcine foetal neural tissue expressed
      moderate levels of MCP and CD59 but low or no levels of DAF. Neural tissue from
      porcine foetuses transgenic for human MCP (E174) expressed the transgene but
      failed to significantly inhibit human C3b deposition compared with non-transgenic
      tissue. In contrast, foetal neural tissue from two different human DAF transgenic
      pig lines (A74 and E71) known to express high levels of human DAF on endothelial
      cells, failed to express significant levels of human DAF in foetal neural tissue.
      Complement regulatory proteins such as MCP and CD59 are expressed in the human
      and wild-type embryonic brain but in contrast, DAF is expressed at very low
      levels. Pigs transgenic for human DAF express very low levels of human DAF on
      embryonic neural tissue. In pigs transgenic for human MCP, the transgene is
      expressed at similar levels to that in human embryonic neural tissue but at an
      insufficient level to prevent activation of the complement cascade. Thus
      alternative approaches to reducing complement activation by xenografted neural
      foetal tissue will be required if this process proves to be important in the
      rejection process.

PMID- 14962295
TI  - Relative effects of GAL+ and GALlow/- porcine hematopoietic cells on primate
      platelet aggregation and endothelial cell activation: implications for the
      induction of mixed hematopoietic chimerism in the pig-to-primate model.
AB  - BACKGROUND: The induction of porcine hematopoietic cell chimerism in
      preconditioned baboons has been hampered by the development of thrombotic
      microangiopathy. As pigs that lack expression of Gal alpha 1,3 Gal (Gal) may
      become available in the near future, we have explored the effects of porcine
      hematopoietic cells that express low or no Gal (Gal(low/-)) on baboon platelet
      aggregation and on human umbilical vein endothelial cell (HUVEC) activation.
      METHODS: Porcine mobilized peripheral blood progenitor cells (PBPC; Gal(+)) and
      bone marrow mononuclear cells (BM; Gal(+) or Gal(low/-)) were investigated for
      their potential to (i) induce aggregation of baboon platelets, and (ii) to
      activate endothelial cells as measured by increased expression of vascular cell
      adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E
      selectin on HUVEC. alpha-Galactosidase-treated PBPC were also investigated for
      their effect on platelet aggregation. RESULTS: Gal(+) PBPC and Gal(+) BM cells
      (10(7)) induced aggregation of baboon platelets by 42 and 31%, respectively,
      whereas Gal(low/-) BM cells did not induce any platelet aggregation. alpha
      Galactosidase-treated PBPC induced less platelet aggregation than untreated PBPC.
      Gal(+) PBPC and Gal(+) BM cells (10(7)) increased expression of VCAM-1, ICAM-1
      and E-selectin on HUVEC, whereas Gal(low/-) BM cells did not. CONCLUSIONS: In
      contrast to Gal(+) PBPC or BM, Gal(low/-) BM cells do not induce aggregation of
      baboon platelets or activate HUVEC. The induction of tolerance through mixed
      hematopoietic cell chimerism may be facilitated when alpha-galactosyltransferase
      knockout pigs become available.

PMID- 14962296
TI  - In vitro and in vivo investigation of a novel monoclonal antibody to plasma cells
      (W5 mAb).
AB  - Natural antibodies (Abs), predominantly anti-Gal alpha 1-3Gal (Gal) Abs, in non
      human primates and human beings present a major hurdle to successful pig-to
      primate xenotransplantation. Attempts to inhibit anti-Gal Ab production in naive
      baboons using non-specific immunosuppressive or B cell-specific reagents have
      failed. A new rat monoclonal antibody (W5 mAb) has been generated, which binds to
      all B cells, including memory cells, and to the majority of plasma cells, but not
      to T cells. It has been tested in vitro and in vivo. By immunoprecipitation, W5
      mAb bound a human leukocyte antigen class II (HLA-DR) determinant. Sorting
      splenic or bone marrow W5+ cells resulted in a highly enriched anti-Gal Ab and
      total immunoglobulin (Ig)-secretory population. In vivo studies in baboons
      demonstrated that W5 mAb was safe but, despite the concomitant administration of
      an anti-CD154 mAb to inhibit sensitization, anti-rat Abs were detected within 10
      days and inhibited the effect of the W5 mAb. High levels of W5 mAb were able to
      completely deplete B cells in the blood, but not in lymphoid tissues. Enzyme
      linked spot-forming assay (ELISPOT) demonstrated that only 50 to 60% of secreting
      cells (SC) were depleted in the bone marrow. No reduction in the serum levels of
      anti-Gal Ab was observed. W5 mAb did not cause complete inhibition of anti-Gal Ab
      production, probably as a result of its inability to completely deplete B and
      plasma cells from all lymphoid compartments.

PMID- 14962297
TI  - Control of microbial contamination during surgical harvest of pig renal
      xenografts.
AB  - The pig has been identified as the most likely source of xenograft material for
      clinical use and studies are ongoing to overcome the immunological hurdles of pig
      to-human transplantation. Attention is now being focussed on identifying and
      reducing the potential microbiological hazards associated with this technique.
      Studies have primarily addressed issues surrounding the production and health
      monitoring of xenograft source pigs and none have so far specifically evaluated
      the possible risks of microbial contamination during xenograft harvest. In this
      report, we evaluate the possible routes for contamination of a pig kidney
      xenograft during organ harvest and describe approaches to the control of these
      hazards, including the novel use of a custom designed airtight surgical canopy. A
      standard procedure for microbiological monitoring during xenograft harvest was
      devised and evaluated. This allowed the rapid identification and anti-microbial
      sensitivity testing of any isolated organisms. This would enable an early and
      appropriate pre-emptive treatment of infection because of transmission of pig
      micro-organisms.

PMID- 14962298
TI  - Isolation and partial characterization of Gal alpha-containing
      polyglycosylceramides from porcine tissues.
AB  - Mammalian cell surface carbohydrate antigens are present both as glycoproteins
      and glycolipids. Of the glycolipids, polyglycosylceramides (PGC) have very long
      carbohydrate chains extending out from the cell surface. Hereto, Gal alpha
      terminating xenoantigens in pig tissues have been identified in glycoproteins and
      short chain glycolipids but no studies of the complex PGC have been performed. In
      this communication, we describe the isolation and partial characterization of PGC
      from pig erythrocytes, small intestinal mucosa, kidney and liver. The mucosa,
      kidney and liver PGC fractions contained a complex pattern of Gal alpha antigens
      as shown by immunostaining using the Griffonia Simplicifolia isolectin B(4) while
      no reactivity was found with the erythrocyte PGC fractions. The mucosa PGC
      fractions stained strongly for blood group A antigens while the erythrocyte PGC
      fractions were negative. The presence of Gal alpha-terminating PGC compounds in
      porcine tissue adds further complexity to the distribution of this xenoantigen.
      Due to the long carbohydrate chains, PGC will be important targets for the Gal
      alpha xenoantibodies in pig to human xenotransplantation.

PMID- 14962300
TI  - Human O red blood cells and pig-to-human xenotransplantation.

PMID- 14962299
TI  - Gal alpha 1,3Gal expression on porcine pancreatic islets, testis, spleen, and
      thymus.
AB  - Gal alpha 1,3Gal (Gal) is the first target in antibody-mediated rejection of pig
      to-non-human primate xenograft. Its expression may vary between organs and
      constituents of organs. Gal expression was studied in pancreas, testis, spleen
      and thymus of 22 pigs, with ages ranging from 1 to 22 months. The
      immunoperoxidase technique using the biotinylated lectin, Griffonia simplicifolia
      (IB4), was used. In the pancreas, neither endocrine (islet cells) nor exocrine
      cells expressed Gal. The Sertoli cells in the testis were negative. The spleen
      capsule and trabeculae did not stain for Gal, although both splenic T and B
      lymphocytes expressed Gal (B > T). Thymocytes were weakly positive, whereas
      thymic epithelial cells were negative for Gal. No age-related differences were
      seen in any tissues. Porcine islets of Langerhans, Sertoli cells, and the splenic
      and thymic structural frameworks did not express Gal, and therefore, should be
      relatively resistant to anti-Gal antibody-mediated rejection. The availability of
      pigs deficient in Gal as a source of islets may therefore not be beneficial in
      extending islet graft survival in non-human primate models.

PMID- 14962302
TI  - Transfusion medicine illustrated. Cryoglobulinemia and cutaneous vasculitis.

PMID- 14962303
TI  - Severe deficiency of VWF-cleaving protease (ADAMTS13) activity defines a distinct
      population of thrombotic microangiopathy patients.
AB  - BACKGROUND: Severe deficiency of ADAMTS13 activity is a biologic risk factor for
      thrombotic microangiopathy (TMA). It was hypothesized that severe ADAMTS13
      deficiency is associated with a distinct TMA subpopulation. STUDY DESIGN AND
      METHODS: ADAMTS13 activity before treatment was determined retrospectively in 107
      adult TMA patients treated with plasma exchange. Patients were not clinically
      categorized, but divided between severely deficient (n = 50) and nonseverely
      deficient (n = 57) ADAMTS13 activity. Laboratory and clinical factors before
      treatment were compared between the groups. RESULTS: Median PLT counts were
      44,000 per micro L in nonseverely deficient ADAMTS13 patients and 13,000 per
      micro L in severely deficient ADAMTS13 patients (p < 0.001). Median serum
      creatinine levels were 2.7 mg per dL in nonseverely deficient patients and 1.2 mg
      per dL in severely deficient patients (p < 0.001). In surviving patients, median
      plasma exchange procedures were 9 in nonseverely deficient patients and 14.5 in
      severely deficient patients (p < 0.01). Rates of relapse following remission were
      4 of 47 in nonseverely deficient patients and 16 of 46 in severely deficient
      patients (p < 0.01). Among analyzed factors only mortality rates were not
      significantly different. CONCLUSION: In a heterogeneous population of TMA
      patients treated with plasma exchange, ADAMTS13 activity defined two
      subpopulations with distinct clinical and laboratory features. These results
      suggest that TMA with severe ADAMTS13 deficiency is a distinct pathologic
      process.

PMID- 14962304
TI  - Clinically practical blood volume assessment with fluorescein-labeled HES.
AB  - BACKGROUND: Standard techniques for measuring blood volume (BV) entail
      administering radioactivity and human albumin. This is laborious, expensive, and
      impractical in acute settings. An alternative method suitable for widespread
      routine application was assessed. STUDY DESIGN AND METHODS: Seventy-nine ambulant
      outpatients and 18 intensive care unit (ICU) patients were prospectively
      recruited. Measurements of RBC volume (RCV) and plasma volume (PV) were performed
      with radiochromium-labeled RBCs (51Cr), radioiodinated albumin (125I), and
      fluorescein-labeled HES (FITC-HES). Small molecules overestimate PV because of
      vascular endothelial dysfunction (ED) and increased capillary permeability; a
      reference value for PV was therefore derived with the RCV and Hct. RESULTS: Mean
      PV with 125I dilution was 230 mL (SD, 185 mL) greater than that with FITC-HES in
      outpatients. This difference was more exaggerated, 345 mL (SD, 371 mL), in ICU
      patients likely to have ED. Both the PV measured with FITC-HES and the 125I
      dilution correlated closely with the PV derived with RCV and Hct (r = 0.950 and
      0.925, respectively) in the ICU patients. CONCLUSION: FITC-HES estimates PV more
      accurately than 125I. FITC-HES should replace radioactive tracers for assessing
      BV. Comparing the estimates of PV with molecules of differing molecular weights
      may have clinical utility as an indicator of ED.

PMID- 14962305
TI  - Expression of Fas and Fas ligand on spleen T cells of experimental animals after
      unmodified or leukoreduced allogeneic blood transfusions.
AB  - BACKGROUND: The clonal deletion seen in recipients of allogeneic blood
      transfusion (ABT) refers to the removal of lymphocytes that promote the clearance
      of transfused alloantigens. Interactions between Fas (CD95) and FasL (CD95L) are
      involved in the clonal deletion of T cells and in the down regulation of the
      cytotoxic T-cell activity. STUDY DESIGN AND METHODS: The expression of CD95/95 L
      on spleen T cells of C57Bl/6 mice infused with unmodified ABT, prestorage
      leukoreduced ABT (LR-ABT), or saline was investigated by flow cytometry. The
      numbers of apoptotic spleen cells were evaluated after transfusion using the
      acridine orange and ethidium bromide uptake technique. RESULTS: Compared with
      untransfused animals, mice transfused with ABT showed higher expression of CD95
      (MFI = 94.4 +/- 8.6 vs. 73.1 +/- 7.9, p = 0.02) and CD95L (23.5 +/- 6.9 vs. 8.1
      +/- 2.0, p = 0.008) on CD4+ spleen cells. Expression of CD95 (92.2 +/- 7.5 vs.
      64.9 +/- 7.5, p = 0.007) and CD95L (17.7 +/- 3.6 vs. 8.2 +/- 2.2, p = 0.02) was
      also increased on CD8+ cells of these animals. CD8+ spleen cells from mice
      transfused with ABT showed higher expression of CD95 (92.2 +/- 7.5 vs. 76.9 +/-
      4.0, p = 0.03) and CD95L (17.7 +/- 3.6 vs. 8.3 +/- 1.5, p = 0.03) than cells from
      mice transfused with LR-ABT. The number of apoptotic spleen cells from mice
      transfused with ABT was greater than that from mice infused with LR-ABT (10.9 +/-
      1.3 vs. 6.6 +/- 1.8, p = 0.01) or saline (10.9 +/- 1.3 vs. 6.5 +/- 0.7, p =
      0.001). CONCLUSIONS: The data suggest that ABT up-regulates the expression of
      Fas/FasL on spleen T cells of mice and may promote their apoptosis. These ABT
      associated immunologic alterations can be partially prevented by the
      leukoreduction of the transfused blood.

PMID- 14962306
TI  - Identification of the Kna/Knb polymorphism and a method for Knops genotyping.
AB  - BACKGROUND: DNA mutations resulting in the McCoy and Swain-Langley polymorphisms
      have been identified on complement receptor 1 (CR1)-a ligand for rosetting of
      Plasmodium falciparum-infected RBCs. The molecular identification of the Kna/Knb
      polymorphism was sought to develop a genotyping method for use in the study of
      the Knops blood group and malaria. STUDY DESIGN AND METHODS: CR1 deletion
      constructs were used in inhibition studies of anti-Kna. PCR amplification of Exon
      29 was followed by DNA sequencing. A PCR-RFLP was developed with NdeI, BsmI, and
      MfeI for the detection of Kna/Knb, McCa/McCb, and Sl1/Sl2, respectively. Knops
      phenotypes were determined with standard serologic techniques. RESULTS: A total
      of 310 Malian persons were phenotyped for Kna with 200 (64%) Kn(a+) and 110 (36%)
      Kn(a-). Many of the Kn(a-) exhibited the Knops-null phenotype, that is, Helgeson.
      The Kna/b DNA polymorphism was identified as a V1561M mutation with allele
      frequencies of Kna (V1561) 0.9 and Knb (M1561) 0.1. CONCLUSION: The high
      frequency (18%) of Knb in West African persons suggests that it is not solely a
      Caucasian trait. Furthermore, because of the high incidence of heterozygosity as
      well as amorphs, accurate Knops typing of donors of African descent is best
      accomplished by a combination of molecular and serologic techniques.

PMID- 14962307
TI  - Evidence that Hy- RBCs express weak Joa antigen.
AB  - BACKGROUND: RBCs of the Hy- phenotype have, in the past, been typed as Gy(a+w),
      Hy-, Jo(a-), and RBCs with the Jo(a-) phenotype type Gy(a+), Hy+w, and Jo(a-).
      Anti-Hy and anti-Joa are difficult to identify mainly because appropriate reagent
      RBCs are poorly characterized. Historically, anti-Joa has not reacted with RBCs
      with either phenotype. This report describes a case of an anti-Joa that shows Hy-
      RBCs express some Joa antigen, albeit weakly. CASE REPORT: Anti-Joa was
      identified in a serum sample of a 71-year-old woman. The antibody reacted 1+ to
      2+ by the IAT with all untreated and ficin-treated panel RBCs and did not react
      with Gy(a-) RBCs and Jo(a-) RBCs. Unexpectedly, the serum sample reacted weakly
      with six of eight RBC samples with the Hy- phenotype. The anti-Joa was adsorbed
      onto and eluted from Hy- RBCs, indicating the presence of weak Joa antigen. The
      patient's RBCs typed Gy(a+), Hy+, Jo(a-). DNA studies using PCR-RFLP analysis
      showed the patient to be homozygous for the JO allele, which is consistent with
      the serologically determined Jo(a-) status. CONCLUSION: The DNA and serologic
      evidence of this case show that Hy- RBCs may express low levels of Joa antigen,
      which contradicts previously published data concerning the Joa type of Hy- RBCs.

PMID- 14962308
TI  - Alteration of amino acid residues at the L-chain N-terminus and in
      complementarity-determining region 3 increases affinity of a recombinant F(ab)
      for the human N blood group antigen.
AB  - BACKGROUND: To examine the fine specificity of glycopeptide-specific antibodies,
      this study focused on the human MN blood group system. F(ab) phage display
      methods were previously used to construct an F(ab) family in which the H-chain Fd
      fragment was held constant whereas the L chains were "shuffled." This yielded two
      related F(ab), N92 and NNA7, with low and high affinity for N, respectively.
      Although their L-chain sequences are very similar, sharing 92 percent amino acid
      identity, there are intriguing differences at the N-terminus and in
      complementarity-determining region 3 (CDR3) at positions 89, 91, 92, and 96.
      STUDY DESIGN AND METHODS: Site-directed mutagenesis, ELISA, and hemagglutination
      were used to examine the contributions of these variations to antibody affinity.
      RESULTS: Studies with the N92-S91G and NNA7-G91S mutants demonstrated that the
      Gly at position 91 was critically important for ensuring high affinity. Indeed,
      the affinity of N92-S91G was almost as high as N92TM, in which all four CDR3
      residues were changed to match NNA7. N-terminal L-chain differences were
      surprisingly important in determining affinity. For example, when the N-terminus
      of N92 was changed to match that of NNA7, affinity increased approximately 30
      fold. CONCLUSION: Specific residues at the L-chain N-terminus and in CDR3
      significantly affected F(ab) affinity for N. Future structural studies of these
      F(ab), alone and complexed with this glycopeptide antigen, will provide further
      insights into these phenomena.

PMID- 14962309
TI  - Improved method for fluorescence cytometric immunohematology testing.
AB  - BACKGROUND: A method for accurate immunohematology testing by fluorescence
      cytometry (FC) was previously described. Nevertheless, the use of vacuum
      filtration to wash RBCs and a standard-flow cytometer for data acquisition
      hindered efforts to incorporate this method into an automated platform. STUDY
      DESIGN AND METHODS: A modified procedure was developed that used low-speed
      centrifugation of 96-well filter plates for RBC staining. Small-footprint
      benchtop capillary cytometers (PCA and PCA-96, Guava Technologies, Inc.) were
      used for data acquisition. Authentic clinical samples from hospitalized patients
      were tested for ABO group and the presence of D antigen (n = 749) as well as for
      the presence of RBC alloantibodies (n = 428). Challenging samples with mixed
      field reactions and weak antibodies were included. Results were compared to those
      obtained by column agglutination technology (CAT), and discrepancies were
      resolved by standard tube methods. Detailed investigations of FC sensitivity and
      reproducibility were also performed. RESULTS: The modified FC method with the PCA
      determined the correct ABO group and D type for 98.7 percent of 520 samples,
      compared to 98.8 percent for CAT (p > 0.05). No-type-determined (NTD) rates were
      1.2 percent for both methods. In testing for unexpected alloantibodies, FC
      determined the correct result for 98.6 percent of 215 samples, compared to 96.3
      percent for CAT (p > 0.05). When samples were automatically acquired in the 96
      well plate format with the PCA-96, 98.7 percent of 229 samples had correct ABO
      group and D type determined by FC, compared to 97.4 percent for CAT (p > 0.05).
      NTD rates were 0.9 and 2.6 percent, respectively. Antibody screens were accurate
      for 99.1 percent of 213 samples with the PCA-96, compared to 99.5 percent for CAT
      (p > 0.05). Further investigations demonstrated that FC with the PCA-96 was
      better than CAT at detecting weak anti-A (p < 0.0001) and alloantibodies.
      CONCLUSIONS: An improved method for FC immunohematology testing has been
      described. This assay was comparable in accuracy to standard CAT techniques, but
      had better sensitivity for detecting weak antibodies and was superior in
      detecting mixed-field reactions (p < 0.005). The FC method demonstrated excellent
      reproducibility. The compatibility of this assay with the PCA-96 capillary
      cytometer with plate-handling capabilities should simplify development of a
      completely automated platform.

PMID- 14962310
TI  - Clinical significance of anti-Jra: report of two cases and review of the
      literature.
AB  - BACKGROUND: Jra is a high-frequency antigen seen in all populations, but the
      clinical significance of Jra antibodies is incompletely understood. Two cases are
      reported in which patients with anti-Jra received incompatible transfusions. CASE
      REPORTS: A 69-year-old Japanese man had anti-K and anti-Jra. Despite multiple
      transfusions of Jr(a+), K- RBCs, his clinical course remained stable without
      evidence of hemolysis. A 45-year-old Japanese woman with anti-Jra was transfused
      with two units of Jr(a+) RBCs without clinical evidence of hemolysis. However,
      the same patient received an additional unit of Jr(a+) RBCs 1 week after the
      initial transfusions and, within 6 hours of transfusion, developed signs and
      symptoms of an acute hemolytic transfusion reaction. STUDY DESIGN AND METHODS:
      Routine serologic methods were used to study the patients' RBCs and plasma. A
      monocyte monolayer assay (MMA) was used to determine the potential clinical
      significance of the anti-Jra, where reactivity (R) greater than 5 percent
      indicates potential clinical significance. RESULTS: The anti-Jra in the first
      case had a pretransfusion titer of 32 with a MMA result of 3.3 percent R. No
      clinical or laboratory evidence of hemolysis was seen after transfusion of 4
      units of Jr(a+), K- RBCs. The anti-Jra in the second case had a pretransfusion
      titer of 32 with a MMA result of 24.5 percent R. This patient developed an acute
      hemolytic reaction after transfusion of Jr(a+) RBCs. CONCLUSION: Anti-Jra can be
      clinically significant as demonstrated by acute hemolysis in the second case. The
      MMA accurately predicted the clinical outcome of each case and appears to be a
      useful tool in predicting the biologic behavior of anti-Jra.

PMID- 14962311
TI  - Effect of holding buffy coats 4 or 18 hours before preparing pooled filtered PLT
      concentrates in plasma.
AB  - BACKGROUND: Filtered PLT concentrates (PCs) were prepared in plasma pooling three
      (for children) or six buffy coats (BCs; for adults) after holding them a maximum
      of 4 hours (blood bags collected in the afternoon) or 18 hours (blood bags
      collected in the morning). STUDY DESIGN AND METHODS: With flow cytometry, PCs
      prepared after holding BCs 4 or 18 hours were compared. BCs removed from whole
      blood donations in quadruple bag packs ("top-top") were held 4 or 18 hours before
      pooling them with a sterile connecting device. After the BCs were centrifuged,
      the supernatant was transferred through a BC filter (Autostop, Pall Medical) to a
      CLX bag. Samples for analysis were collected from the whole-blood bag, BCs, and
      PCs immediately after preparation and after 1, 3, 5, and 7 days of storage on a
      flat-bed agitator at 22 +/- 2 degrees C. The main PLT membrane glycoproteins
      (GPs, IIb-IIIa, IV, and Ibalpha), some of their ligands (fibrinogen, fibronectin,
      and VWF), activation-dependent antigens (CD62P and CD63), and procoagulant
      activity markers (annexin V and bound coagulation FV-Va) have been studied.
      RESULTS: In the 12 PCs (six pools of 3 units each group) studied, a minor
      increase in activation markers during preparation was observed. During the
      storage, a significant increase in the expression of GPIIb-IIIa, CD62P, CD63,
      annexin V, and FVa was measured. After 5 days of storage, only the percentage of
      PLTs with bound fibrinogen was significantly greater in PCs prepared after
      holding BCs for 4 hours. CONCLUSION: In PCs prepared after holding BCs 4 or 18
      hours before pooling and filtering, only a minor significant difference in the
      percentage of PLTs with bound fibrinogen was found after 5 days of storage. This
      difference is probably of little, if any, transfusional significance.

PMID- 14962312
TI  - New insulation technology provides next-generation containers for "iceless" and
      lightweight transport of RBCs at 1 to 10 degrees C in extreme temperatures for
      over 78 hours.
AB  - BACKGROUND: There is a universal need, in both civilian and military settings,
      for a lightweight container capable of maintaining RBCs at 1 to 10 degrees C in
      remote areas, during extended transit times, and under austere environments. The
      use of ice in insulated containers or small commercial coolers for these purposes
      often results in loss of RBCs due to failure to maintain temperatures within the
      requisite range. A lightweight and thermally efficient container capable of
      carrying 4 to 6 units of RBCs at 1 to 10 degrees C for over 72 hours under
      extreme conditions would help resolve current problems in RBC transportation.
      STUDY DESIGN AND METHODS: Six different prototype containers incorporating phase
      change materials (PCMs) in their designs were evaluated for their ability to
      maintain RBCs between 1 and 10 degrees C while exposed to external temperatures
      of -24 degrees C and 40 degrees C. In separate experiments, a container was
      opened and a RBC unit removed. RESULTS: One container weighing 10 pounds with
      four units of RBCs was capable of maintaining the temperature of the units
      between 1 and 10 degrees C for over 78 hours, 96 hours, and 120 hours at 40
      degrees C, -24 degrees C, and 23 degrees C, respectively. Opening the container
      decreased these times by 2 to 3 hours. CONCLUSIONS: An energy-efficient and
      lightweight container that maintains RBCs at 1 to 10 degrees C under austere
      environments for over 78 hours is now available. This container, known as the
      Golden Hour container (GHC), will facilitate transport of RBCs. The GHC will have
      additional applications (transport and/or storage of vaccines, other biologics,
      organs, reagents, etc).

PMID- 14962313
TI  - The cost-effectiveness of screening blood donors for malaria by PCR.
AB  - BACKGROUND: The cost-effectiveness of four blood donor screening strategies for
      malaria was estimated to determine whether transmission by transfusion can be
      reduced. STUDY DESIGN AND METHODS: A decision analysis model was developed to
      compare 1) not screening allogeneic blood donors for malaria (Strategy 1); 2)
      using the standard questionnaire (Strategy 2); 3) using the standard
      questionnaire followed by testing blood donors with risk factors for malaria with
      PCR (Strategy 3); and 4) screening all blood donors using PCR (Strategy 4). The
      expected costs and the number of cases of malaria for each strategy were compared
      and incremental cost-effectiveness ratios were calculated as the cost per case of
      malaria averted. All costs are in Canadian dollars. RESULTS: Strategies 2 and 3
      had the same effectiveness but different costs, with Strategy 3 being less
      costly. Compared to Strategy 1, the incremental cost effectiveness ratio was 6463
      dollars per case of malaria averted for Strategy 3. Strategy 4 resulted in less
      transmission of malaria (0.4/million donors), but the cost compared to Strategy 3
      was 3,972,624 dollars per case of malaria averted. CONCLUSION: The addition of
      PCR to the standard screening questionnaire is economically attractive compared
      to the current standard screening questionnaire.

PMID- 14962314
TI  - Pediatric large-volume leukapheresis: a single institution experience with
      heparin versus citrate-based anticoagulant regimens.
AB  - BACKGROUND: Anticoagulant-associated toxicity may exert significant effects on
      the safety and efficacy of large-volume leukapheresis (LVL) in children, however,
      few studies specifically address management of this issue. STUDY DESIGN AND
      METHODS: Seventy-four consecutive LVL procedures (mean, 4 blood volumes
      processed) in children weighing less than or equal to 30 kg (minimum, 10.9 kg)
      were analyzed. The first 21 procedures were evaluated retrospectively; 11 used
      heparin alone (Group I) and 10 used heparin plus reduced-dose ACD-A (whole blood
      to anticoagulant ratio > or =20:1) (Group II). The next 53 procedures were
      evaluated prospectively and used full-dose ACD-A (whole blood to anticoagulant
      ratio < or =13:1), intravenous divalent cation prophylaxis and no heparin; 11
      used calcium alone (Group III) followed by 42 with calcium plus magnesium (Group
      IV). RESULTS: Seventy-four LVL (56 PBPC and 18 MNC) collections were performed in
      38 subjects. One donor in Group I experienced a significant groin hematoma at the
      site of line placement. One donor each in Groups III and IV had mild
      paresthesias. Despite a mean citrate infusion rate of 2.6 mg per kg per minute,
      mean postapheresis serum potassium and ionized magnesium and calcium
      concentrations in Group IV declined by only 9, 8, and 4 percent, respectively,
      and stable levels of these variables were maintained 24 hours later.
      Postapheresis PLT counts declined significantly from baseline preapheresis levels
      in all groups (mean, 52% decrease). CONCLUSIONS: Use of full-dose citrate
      anticoagulant with prophylactic intravenous divalent cation infusion offers an
      effective and safe approach to management of anticoagulant-related toxicity in
      children undergoing LVL.

PMID- 14962315
TI  - The translocation of marrow MNCs after experimental myocardial cryoinjury is
      proportional to the infarcted area.
AB  - BACKGROUND: The selective homing of peripherally injected marrow MNCs (MMNCs) has
      recently been demonstrated in a model of cryodamaged heart. However, the
      mechanism underlying this phenomenon is still unknown. In the hypothesis that
      this process is related to the necrotic area extension, the infarcted area was
      correlated with the number of homed MMNCs in a model of experimental cryodamaged
      heart. STUDY DESIGN AND METHODS: A total of 12 donor and 12 recipient inbred
      isogenic adult (4 weeks old) Fisher rats were used to mimic autologous
      transplantation. Myocardial damage was obtained in recipient rats by cryoinjury.
      MMNCs were purified, labeled with PKH26 (a red fluorescent cell dye), and infused
      7 days after the injury through the femoral vein of recipient rats. One week
      after peripheral administration, the number of homed MMNCs was assessed and the
      infarct size was correlated with the number of cells present in the target.
      RESULTS: Labeled cells were found only in the injured myocardium of the treated
      animals (n = 6), where a mean of 12 +/- 3 PKH26+ cells per section examined were
      found; a significant correlation was found between the infarct size and the
      estimated number of cells (p = 0.008) CONCLUSION: These data indicate that the
      homing of MMNCs is related to the extent of the myocardial injury, suggesting
      that cellular therapy for regeneration of damaged myocardium should be
      individualized by taking into consideration the extension of the area to repair.

PMID- 14962316
TI  - Retention of cellular properties of PBPCs following liquid storage and
      cryopreservation.
AB  - BACKGROUND: G-CSF-mobilized PBPCs are routinely cryopreserved within 24 hours of
      collection. The ability to hold PBPCs for extended time would offer increased
      flexibility for patients and hospitals. Retention of PBPC properties following
      overnight shipping, extended liquid storage at 1 to 6 degrees C, and
      cryopreservation was evaluated. STUDY DESIGN AND METHODS: PBPCs were stored in
      liquid at 1 to 6 degrees C up to 3 days, with and without shipping, and then
      cryopreserved in HES (6%), DMSO (5%), and HSA (4%). Thawed samples were assayed
      after two procedures, on dilution and after dilution and washing. Nucleated
      cells, viability, CD34+ cell number, committed progenitor colonies, and long-term
      culture-initiating cells were measured. RESULTS: CD34+ cell number, committed
      colony-forming cells, and long-term culture-initiating cells were essentially
      maintained when samples were stored in liquid for 1, 2, or 3 days before
      cryopreservation or after thawing and dilution. Nevertheless, significant (p <
      0.05, paired t test) losses in total nucleated cell numbers were observed if
      thawed PBPC samples were washed before assay. CONCLUSION: PBPCs can be maintained
      at 1 to 6 degrees C for up to 3 days and can be cryopreserved after extended
      storage with properties minimally altered. Dilution alone, without centrifugation
      and washing, of thawed PBPC samples is a satisfactory procedure for preparing
      samples for in vitro assays.

PMID- 14962317
TI  - Engraftment of autologous and allogeneic marrow HPCs after myeloablative therapy.

PMID- 14962318
TI  - Analysis of maternal and neonatal factors that influence the nucleated and CD34+
      cell yield for cord blood banking.
AB  - BACKGROUND: It would be beneficial to be able to predict the cord blood (CB) cell
      yield from volunteer donors before cell processing. STUDY DESIGN AND METHODS: The
      maternal and neonatal factors that influence the total nucleated cell (TNC),
      CD34+ cell, and CFU-GM yields in CB collected for the Chugoku-Shikoku Cord Blood
      Bank were evaluated. RESULTS: In a univariate analysis, the volume of CB
      collected was significantly correlated with the TNC, CD34+ cell, and CFU-GM
      yields (p < 0.001). A longer cord (p < 0.001), larger placenta (p < 0.001), and
      bigger baby (p < 0.001) were associated with a greater volume of CB. A female
      baby (p < 0.05) and longer gestational age (p < 0.005) were associated with a
      higher TNC concentration. A younger maternal age (p < 0.05), larger birth weight
      (p < 0.001), shorter gestational age (p < 0.001), and shorter time from
      collection to processing (p < 0.05) were associated with a higher CD34+ cell
      concentration. A multivariate linear regression analysis was performed to predict
      the yield and determine first-level selection criteria to start processing when
      the volume of CB units was on the borderline. However, this formula might not be
      suitable for actual use. CONCLUSION: Maternal and neonatal factors appeared to
      affect CB cell yields. These findings might be useful for efficiently collecting
      more qualified CB units.

PMID- 14962320
TI  - Risk factors for HCV infection among blood donors confirmed to be positive for
      the presence of HCV RNA and not reactive for the presence of anti-HCV.
AB  - BACKGROUND: In 1999, NAT of blood donations was implemented to detect "window
      period" infections. Blood donors who have confirmed NAT results positive for the
      presence of HCV in the absence of anti-HCV are likely to have been recently
      infected. Of over 26.8 million donations tested between March 3, 1999, and March
      31, 2003, 810 were HCV-reactive by NAT. A subset of these donors was assessed for
      recent exposure risk. STUDY DESIGN AND METHODS: All anti-HCV- blood donors with
      reactive, unconfirmed HCV NAT results were invited to participate in a study that
      included an extensive demographic and risk questionnaire. Confirmed HCV+ cases
      were compared to HCV- (falsely positive) controls for histories of potential risk
      factors during the 6 months before donation. RESULTS: Recent injection drug use
      (IDU) was independently associated with HCV infection (29.2% vs. 0% of cases vs.
      controls, p < 0.001). In addition, likely sources were identified for three other
      cases (4.6%), including occupational exposure, sexual contact with an HCV
      infected partner (who was an IDU), and perinatal exposure, none of which was
      known to the donors at the time of donation. Incarceration was independently
      associated with HCV infection among the group not reporting IDU and after removal
      of the three donors with likely sources of risk (14.6% vs. 1.3% of cases vs.
      controls, p < 0.001). CONCLUSIONS: A likely risk, primarily IDU, was found for 43
      percent of HCV+ donors whose infections were identified solely by NAT. Because
      the maximum efficiency of the donor history questions may have been reached, NAT
      will continue to be an important measure to interdict recently infected blood
      donors.

PMID- 14962319
TI  - High prevalence of GBV-C/HGV among relatives of GBV-C/HGV-positive blood donors
      in blood recipients and in patients with aplastic anemia.
AB  - BACKGROUND: The prevalence of GB virus C (GBV-C)/HGV is high in individuals with
      parenteral risk factors. The frequency of GBV-C/HGV in blood donors is
      significantly lower, however it is still far above other parenterally transmitted
      viruses like HBV and HCV. Therefore, transmission routes apart from parenteral
      transmission must be considered. STUDY DESIGN AND METHODS: The purpose of the
      study was to evaluate the prevalence of GBV-C/HGV in blood donors and relatives
      of GBV-C/HGV-positive and -negative blood donors. Prevalence was also analyzed in
      aplastic anemia patients. Samples were tested by RT-PCR and partially by ELISA.
      Positive isolates were sequenced and phylogenetically analyzed. RESULTS: A total
      of 5733 blood donors were PCR tested and 90 were positive (1.6%). Of these, 98
      relatives could be tested. Viremia was found in 14.3 percent and anti-E2 in 29.5
      percent, whereas only 1.1 percent of the relatives of PCR-negative donors were
      viremic and 8.5 percent were anti-E2 positive. Probable virus transmission could
      be shown in two couples and in six mother-child pairs by sequencing of isolates
      indicating horizontal and vertical virus transmission, respectively. Recipients
      of GBV-C/HGV RNA-positive blood products were shown to be infected at a rate of
      58 percent (18/31). Aplastic anemia patients were positive at a rate of 32
      percent (17/53). CONCLUSION: The high percentage of 14.3 percent of GBV-C/HGV PCR
      positive relatives of GBV-C/HGV-positive blood donors suggests intrafamilial
      transmission. Sequence analyses revealed vertical and horizontal transmission.
      Although parenteral transmission is highly efficient for GBV-C/HGV (58% of
      recipients of GBV-C/HGV RNA-positive blood products and 32% of aplastic anemia
      patients), it appears that sexual and vertical transmission are the most common
      transmission routes.

PMID- 14962321
TI  - Inhibition of xenogeneic GVHD by PEN110 treatment of donor human PBMNCs.
AB  - BACKGROUND: Development and characterization of methods for preventing
      transfusion-associated GVHD have utilized in vitro studies with human WBCs and in
      vivo studies in animal models. The limitation of these assays is that the in vivo
      GVHD response of treated human WBCs has not been tested directly. STUDY DESIGN
      AND METHODS: PBMNCs isolated from nonleukoreduced RBC units exposed to gamma
      irradiation, treated with PEN110 or PBS, were tested for their ability to induce
      xenogeneic GVHD when injected into severe combined immunodeficient (SCID) mice.
      RESULTS: These studies showed that the SCID mice injected with PBS-treated PBMNCs
      developed serum levels of human immunoglobulin that were followed by weight loss
      and display of ruffled fur characteristic of xenogeneic GVHD in these mice. In
      contrast, SCID mice injected with PEN110-treated or gamma-irradiated PBMNCs did
      not exhibit any of these responses. CONCLUSIONS: In these studies PEN110
      treatment and gamma irradiation were equally effective at preventing in vivo GVHD
      responses when the treated cells were injected into SCID recipients. These
      results are consistent with previous results obtained when these two treatment
      methods were compared with in vitro studies with PBMNCs and in vivo studies in
      mouse models.

PMID- 14962322
TI  - Inactivation of mycoplasma species in blood by INACTINE PEN110 process.
AB  - BACKGROUND: Mycoplasmas have been associated with multiple acute and chronic
      diseases. Mycoplasma genome is found in the blood of 10 to 15 percent of
      subjectively healthy individuals. If blood borne and viable in donated blood,
      mycoplasmas could potentially be transfusion transmissible. The INACTINE PEN110
      technology is a pathogen reduction process that is in Phase 3 clinical studies.
      The present study investigated the ability of this process to eradicate
      mycoplasmas in human blood. STUDY DESIGN AND METHODS: Identical whole blood or
      RBC units inoculated with Mycoplasma arthritidis or M. pneumoniae were incubated
      with PEN110 (inactivating agent) for 24 hours at 23 degrees C. Sham controls were
      treated with buffer under the same conditions. 4 degrees C controls were put on
      storage immediately after the spike. RESULTS: No viable microorganisms were
      detected in PEN110-treated units after 24 hours of incubation. Sham controls
      showed no changes to mycoplasma titers during the incubation. In 4 degrees C
      controls, minor decrease of mycoplasma titers was observed during the storage.
      CONCLUSION: The INACTINE process inactivates more than 107 mycoplasma CFU per mL
      in whole blood and RBCs. This study is the first demonstration of susceptibility
      of mycoplasmas to pathogen reduction. The data provide further support for the
      ability of INACTINE technology to address microbial safety issues that are not
      well characterized.

PMID- 14962323
TI  - Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome following
      allogeneic HPC transplantation: a diagnostic dilemma.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP
      HUS) has been described as a specific sequela of allogeneic HPC transplantation
      (HPCT). Nevertheless, because multiple transplant-related sequela can cause the
      characteristic clinical features of TTP-HUS, the diagnosis is difficult. STUDY
      DESIGN AND METHODS: All English-language articles describing patients with TTP
      HUS following HPCT were identified. Articles reporting five or more total
      patients, including at least one patient diagnosed with TTP-HUS following
      allogeneic HPCT, were reviewed. All articles describing autopsies of patients
      diagnosed with TTP-HUS following allogeneic HPCT were also reviewed. RESULTS:
      Thirty-five articles reporting 5 or more total patients described 447 patients
      diagnosed with TTP-HUS following allogeneic HPCT. The frequency of diagnosis of
      TTP-HUS following allogeneic HPCT varied by 125-fold (0.5%-63.6%). Twenty-eight
      different sets of diagnostic criteria were described in the 35 articles; 25
      articles included both RBC fragmentation and increased serum LDH. Many risk
      factors described as correlating with the diagnosis of TTP-HUS also predict
      greater risk for multiple transplant-related complications. Benefit of plasma
      exchange treatment could not be documented. Survival information was reported for
      379 patients, 232 (61%) died, and reported mortality rates varied from 0 to 100
      percent. Autopsies have been reported for 35 patients who were diagnosed with TTP
      HUS following allogeneic HPCT; none had systemic thrombotic microangiopathy, the
      diagnostic abnormality of TTP-HUS; and infection (19 patients) was the most
      commonly reported cause of death. CONCLUSIONS: The clinical features of TTP-HUS
      following allogeneic HPCT may be caused by common transplant-related
      complications; the benefit from plasma exchange treatment is uncertain.

PMID- 14962324
TI  - Lack of the Cromer antigen GUTI in Mexican Americans and Choctaw Indians.

PMID- 14962325
TI  - HCV core antigen as an alternative to NAT to detect HCV viremia.

PMID- 14962326
TI  - Monitoring outcome in paediatric intensive care.

PMID- 14962327
TI  - Conjoined twins--the anaesthetic management of 15 sets from 1991-2002.
AB  - The Red Cross War Memorial Children's Hospital, Cape Town, South Africa is the
      only dedicated children's hospital in sub-Saharan Africa and, as such, is the
      referral hospital for complex procedures from this region. Fifteen sets of
      conjoined twins have presented for separation from 1991 to 2002, and a total of
      34 sets since 1964. Anaesthesia for procedures on conjoined twins is a demanding,
      exacting and meticulous exercise, whether prior to or during separation.
      Anaesthesia forms part of the multidisciplinary management of the babies.
      Emphasis is laid on preoperative assessment, goal-directed planning of theatre
      and the staff involved in the surgery, duplication of all equipment necessary for
      anaesthetizing and monitoring two infants in one operating room, and having plans
      in place to avoid overcrowding. Challenges encountered in anaesthesia for these
      twins include identifying anatomical conjunctions, airway management, acquiring
      vascular access, the potential for enormous blood loss, and maintaining
      normothermia. Planning for the postseparation period and the reconstruction and
      rehabilitation of the babies is essential from the time of their initial
      admission. Meticulous attention to detail, monitoring and vigilance are
      mandatory. Successful management of conjoined twins relies on close communication
      and cooperation of all members of the multidisciplinary team.

PMID- 14962328
TI  - Influence of control variables on mannequin temperature in a paediatric operating
      theatre.
AB  - BACKGROUND: Core temperature drops in all children having general anaesthesia.
      Convection heating may be useful, but its effectiveness in the paediatric setting
      is not established. Additionally, its utility in many paediatric situations is
      limited by blanket design. METHODS: Using a mannequin model in a sham operation,
      we assessed the likely safety and effectiveness of a draping technique in
      association with a 'Bair Hugger' and a heat dissipation unit (HDU). In Part 1 of
      the study, the influence of ambient temperature was assessed. In Part 2, a
      simulated laparotomy was set up and a more detailed assessment of air
      temperatures around the mannequin was made. In addition, the effect of a change
      in the HDU design was assessed. RESULTS: Part 1: the technique achieved 'near
      plateau' temperature within 5-10 min. A difference of 8 degrees C in ambient
      temperature (between 18 and 26 degrees C) translated only to a 2-3 degrees C
      difference under the drapes. Part 2: the technique produced sidestream cooler
      zones at the head and shoulders. Air temperature at these sites was 28-34 degrees
      C, whereas at other points (irrespective of their distance from the heat source),
      it was 37-40 degrees C. Warm air reached sufficient skin sites to anticipate
      adequate heat transfer in the clinical situation. Air temperature at 'skin'
      surface stayed below 40 degrees C over the 90-min study period. CONCLUSIONS: A
      customized HDU used in association with a 'Bair Hugger' unit and a careful
      surgical draping technique provides stable, safe and consistent air temperatures
      around a mannequin. Net heat gain by a child's body should occur with this
      arrangement. Further evaluation in a clinical study is underway.

PMID- 14962329
TI  - Clinical and biochemical effects of propofol EDTA vs sevoflurane in healthy
      infants and young children.
AB  - BACKGROUND: Propofol is frequently used for the induction and maintenance of
      anaesthesia in children aged 3 years and older. The present study compared the
      clinical and chemical effects of propofol containing disodium edetate (Diprivan)
      with that of sevoflurane in children younger than 3 years of age. METHODS: This
      was an open-label, comparative, parallel-group study. Fifty-six healthy children
      were randomly assigned to receive either propofol (n=28; mean age 14.7 months) or
      sevoflurane (n=28; mean age 13.2 months) for ambulatory surgical procedures.
      Anaesthesia was induced with nitrous oxide (60%), oxygen and sevoflurane (8%). In
      the propofol group, it was followed by an intravenous infusion of propofol at a
      rate of 200 microg.kg(-1).min(-1). For the sevoflurane group, anaesthesia was
      maintained with sevoflurane (1.5-2.5%). Haemodynamic measurements, recovery time
      and side-effects were recorded. Ionized calcium and magnesium concentrations in
      blood were measured. Statistical analysis was performed using ancova and the
      Fisher's exact test. RESULTS: The effects of propofol were similar to those of
      sevoflurane with respect to haemodynamic profile, recovery times (20 min vs 19.4
      min) and side-effects (i.e. vomiting 10.7% vs 7.1%). Throughout the study, there
      were no significant differences between the mean ionized calcium and ionized
      magnesium concentrations in the two groups. CONCLUSIONS: In children younger than
      3 years of age, propofol containing ethylenediaminetetraacetic acid has a similar
      profile to sevoflurane with respect to haemodynamic effects, recovery times, side
      effects, ionized calcium and ionized magnesium levels.

PMID- 14962330
TI  - Electroencephalograph variables, drug concentrations and sedation scores in
      children emerging from propofol infusion anaesthesia.
AB  - BACKGROUND: Inadequate sedation or oversedation are common problems in Paediatric
      Intensive Care because of wide variations in drug response and the lack of
      objective tests for sedative depth. We undertook a pilot study to try to identify
      correlates of propofol drug concentration, electroencephalographic (EEG)
      variables and observed behaviour during a stepwise reduction in propofol infusion
      after paediatric cardiac surgery. METHODS: This was a prospective pilot study
      with 10 children (5 months to 8 years) emerging from propofol anaesthesia
      following cardiac surgery with cardiopulmonary bypass (CPB). Patients underwent a
      stepped wake-up from propofol anaesthesia during which the propofol infusion rate
      was decreased from 4 mg.kg(-1).h(-1) in 1 mg.kg(-1).h(-1) steps at 30 min
      intervals. EEG variables, propofol blood concentrations and clinical sedation
      scores (COMFORT scale) were recorded during the stepped wakeup. Analgesia was
      maintained with a standardized continuous infusion of fentanyl. RESULTS: : Mean
      (SD) whole blood propofol concentrations at arousal varied considerably [973
      ng.ml(-1) (SD 523 ng.ml(-1))]. The summed ratio (SR) of high frequency to low
      frequency bands correlated with both propofol infusion rate (R2 value=0.47) and
      propofol blood concentrations (R2 value=0.64). The mean SR in deeply sedated
      patients was significantly different from that in the 5 min prior to wakening
      (6.84 vs 1.55, P=0.00002). There was no relationship between COMFORT scores and
      SR. CONCLUSIONS: In this group of patients receiving opioid analgesia and
      relatively high doses of propofol, sedation scores were unhelpful in predicting
      arousal. The SR correlated with propofol blood concentrations and clinical
      arousal and may have potential as a predictive tool for arousal in children.

PMID- 14962331
TI  - The clinical effect of mixing different proportions of rocuronium and mivacurium.
AB  - BACKGROUND: A synergistic effect has been described when rocuronium (Roc) and
      mivacurium (Miv) are combined in equal (i.e. 1:1) ED95 proportions at various
      total doses. We have investigated the effect of Roc or Miv alone and four
      different ratios (1:4, 2:3, 3:2 and 4:1) of Roc and Miv mixed to a total dose of
      1.33 x ED95. The primary outcome is the ratio producing the maximum enhancement
      of duration of clinical effect. METHODS: Sixty-eight healthy children were
      anaesthetized with propofol, nitrous oxide and fentanyl. They then randomly
      received either Roc 0.4 (mg.kg(-1)), Miv 0.133 (mg.kg(-1)) or one of four Roc +
      Miv combinations (mg.kg(-1)): Roc 0.32 + Miv 0.027; Roc 0.24 + Miv 0.053; Roc
      0.16 + Miv 0.08; and Roc 0.08 + Miv 0.106. The mechanical response of the
      adductor pollicis muscle to supramaximal stimulation of the ulnar nerve at the
      wrist was recorded. RESULTS: Duration of effect was greater in the combination
      groups than that predicted from the duration of Roc or Miv used alone. Duration
      was maximally increased around a 1:1 ratio (2:3 and 3:2) of Roc and Miv. The
      likelihood of achieving 100% block was greater in combination groups compared
      with Roc or Miv used alone. CONCLUSIONS: Combinations of Roc and Miv show a
      synergistic effect, which appears maximal as the mixture approaches a 1:1 ratio
      of their ED95s. This combination acted as if a larger effective dose of a single
      (new) drug had been given, but did not offer the advantage of both rapid onset
      and short duration of effect.

PMID- 14962332
TI  - Perioperative anaesthetic morbidity in children: a database of 24,165
      anaesthetics over a 30-month period.
AB  - BACKGROUND: This study reports the practices and morbidity of 24,165 anaesthetics
      performed over a 30-month period in a paediatric teaching hospital. METHODS: Data
      describing practices and adverse events during anaesthesia and in the
      postanaesthesia care unit (PACU) were collected prospectively from 1 January 2000
      to 30 June 2002 on an audit form as a part of the Quality Assurance Program. All
      surgical specialties are covered except for open heart surgery and neurosurgery.
      RESULTS: A total of 724 adverse events were reported during anaesthesia and 1105
      in PACU. Respiratory events represented 53% of all intraoperative events. They
      were more frequent in infants compared with older children, in ENT surgery
      compared with other surgery, in children in whom the trachea was intubated and in
      children with ASA status 3-5 compared with those with ASA score 1 or 2. Cardiac
      events accounted for 12.5% of intraoperative events and were mainly observed in
      children with ASA score 3-5. In PACU, vomiting was the most frequent adverse
      event with an overall incidence of 6%. Vomiting was more frequent in older
      children compared with infants and young children and more frequent after ENT
      surgery compared with other surgery. Only one death was reported in a premature
      newborn infant and was not anaesthesia-related. CONCLUSIONS: This observational
      study confirms previous reports, and indicates that there is still a relative
      higher rate of adverse events in infants compared with older children even in a
      teaching paediatric hospital with a high annual caseload.

PMID- 14962334
TI  - Anaesthetic management in a neonate with congenital complete heart block.
AB  - We present the case of a neonate undergoing surgery on the first day of life for
      the installation of a permanent pacemaker because of the existence of congenital
      complete heart block (CCHB) with a basal heart rate of 43 b.min(-1) and minimal
      elevation after initiating an isoproterenol perfusion. The intervention was under
      general anaesthesia with laryngeal mask airway (LMA) and spontaneous ventilation.
      The principal anaesthetic goals were to assure adequate anaesthesia, with
      haemodynamic and respiratory stability, to maintain the best possible heart rate
      and to avoid postoperative respiratory depression or apnoea.

PMID- 14962333
TI  - Transcutaneous carbon dioxide monitoring during diabetic ketoacidosis in children
      and adolescents.
AB  - OBJECTIVE: Our aim was to evaluate the utility of transcutaneous CO2 (TC-CO2)
      monitoring in following the response to therapy in children and adolescents in
      diabetic ketoacidosis (DKA) requiring ICU admission. METHODS: During therapy for
      DKA, TC-CO2 was monitored and compared with the serum bicarbonate values (HCO3-).
      As clinically indicated, serum electrolytes including serum HCO3- were drawn and
      at the same time, the TC-CO2 value was recorded. Using the TC-CO2 value and the
      equation (PaCO2=1.5xHCO3-+8), a calculated HCO3- value was determined. The
      measured serum HCO3- value was subtracted from the calculated HCO3- value and the
      absolute difference was recorded. The difference between the measured serum HCO3-
      and the calculated HCO3- was analysed using analysis of variance after
      stratification for serum HCO3- values and patient age ranges. Calculated to serum
      HCO3- values were compared using linear regression analysis. In addition, serum
      HCO3- values were plotted against TC-CO2 values to derive an equation from these
      data which would relate the TC-CO2 values to the measured serum HCO3-. RESULTS:
      The cohort included 28 patients ranging in age from 1.6 to 21 years (9.4 +/- 4.7
      years) and in weight from 13 to 96 kg (35.6 +/- 18.2 kg). Two additional patients
      were not included as the initial TC-CO2 values were inaccurate because of tissue
      hypoperfusion. In the remaining 28 patients, the absolute difference between the
      calculated bicarbonate and serum bicarbonate values was 1.5 +/- 1.2 mmol.l-1. The
      difference was < or =2 mol.l in 74.4% of samples and < or=5 mmol.l(-1) in 99.2%.
      No difference in the value between the calculated and measured serum HCO3- was
      present according to serum HCO3- value or patient's age. Linear regression
      analysis of calculated HCO3- against serum HCO3- revealed a slope of 0.95 and an
      r2 value of 0.88. Linear regression analysis using serum HCO3- against TC-CO2
      resulted in the following equations: TC-CO2=(1.64xHCO3-)+3.9 or HCO3-=0.61x(TC
      CO2-3.9). CONCLUSIONS: TC-CO2 correlates with serum HCO3- and can be used to
      follow therapy in children and adolescents in DKA.

PMID- 14962335
TI  - Anaesthetic experiences in three sets of conjoined twins in King Chulalongkorn
      Memorial Hospital.
AB  - We describe the anaesthetic management for magnetic resonance image scanning,
      angiography and surgical operations in three sets of conjoined twins
      (ischiopagus, throracopagus and pygopagus) in King Chulalongkorn Memorial
      Hospital during 1996-2002. The anaesthetic technique and associated problems are
      summarized.

PMID- 14962336
TI  - Peripherally inserted central venous catheters in preterm newborns: two unusual
      complications.
AB  - This report describes the case of two newborns who suffered unusual complications
      after peripheral insertion of a central venous catheter. In one baby a fragment
      of the catheter tip became embolized in a peripheral branch of the left pulmonary
      artery. In the other baby, the catheter perforated a peripheral branch of the
      pulmonary artery, giving rise to chemical pneumonitis with extensive pleural
      effusion. The outcome was positive for both babies. A large clinical series is
      necessary to establish the complications of this procedure, their prevention and
      management.

PMID- 14962337
TI  - The laryngeal mask airway for administration of surfactant in two neonates with
      respiratory distress syndrome.
AB  - We report the successful use of the Classic laryngeal mask airway to provide
      brief access to the intratracheal space for the administration of surfactant in
      two neonates with respiratory distress syndrome.

PMID- 14962338
TI  - Anaesthetic considerations in the management of heteropagus twins.

PMID- 14962339
TI  - Continuous thoracic epidural analgesia with 0.2% ropivacaine for pectus excavatum
      repair in children.

PMID- 14962340
TI  - Sevoflurane for general anaesthetic management in a patient with Larsen syndrome.

PMID- 14962342
TI  - Caring holistically within new managerialism.
AB  - This article explains the attempts of nurses to practice humanistic, holistic
      care in line with their professionalizing strategy. Ideally, the intention of
      nurses is to broaden their concerns beyond the physiological needs of patients,
      thereby circumventing biomedical control over their work. However, the author
      argues that resource constraints, and the coalescing of biomedical and managerial
      definitions of patients, suggest that holistic notions of care are subjected to a
      new form of calculus and normalizing technology. Critically, nurses are more
      preoccupied with the day-to-day struggle to free up resources for healthcare, in
      particular bed spaces, and to pre-empt the problem of bed blocking. Such work
      suggests that the "emptying of beds" is not just a symbol of accomplishment for
      nursing work. From the governmentality theory of Foucault, the administration of
      "beds" has become part of the managerial power/knowledge discourse and an
      instrument for making nurses toe the financial bottom-line.

PMID- 14962343
TI  - Ethnomethodological insights into insider-outsider relationships in nursing
      ethnographies of healthcare settings.
AB  - This article re-examines insider-outsider relationships in nursing ethnographies
      of healthcare settings as a case study in the wider sociological debate around
      reflexivity in field research. It focuses on the practices through which the
      fieldwork role is accomplished and the "identity work" of nurse ethnographers.
      Insights derived from ethnomethodology are utilized in order to analyse selected
      aspects of real-life field experiences in order to enhance our understanding of
      this relatively neglected dimension of the research process. The article is
      offered as a contribution to an emerging body of scholarship that is directed at
      promoting a more rigorous and theoretically informed understanding of the conduct
      and reportage of ethnographic fieldwork.

PMID- 14962344
TI  - Researching emotion: the need for coherence between focus, theory and
      methodology.
AB  - There is a longstanding awareness of the significance of emotion in nursing and
      yet it remains one of the more elusive areas of practice. Surprisingly, there has
      been little discussion in the nursing literature of how the phenomenon of emotion
      might be understood or studied. This paper gives an overview of theoretical and
      methodological approaches to emotion, and how the researcher's emotions may
      inform the research process. In addition, it draws on ethnographic research
      exploring the role of emotion in the practice and clinical supervision of a group
      of psychosexual nurses undergoing Balint seminar training to help highlight some
      of the inherent problems of researching emotion. The paper argues that these
      sorts of problems may be avoided or reduced by ensuring coherence between the
      research focus, the way emotion is theorised, and the methodological approach of
      the study.

PMID- 14962345
TI  - Aoteaoroa/New Zealand nursing: from eugenics to cultural safety...
AB  - The concept of cultural safety offers a unique approach to nursing practice,
      based on recognition of the power differentials inherent in any interaction. It
      is from within the context of nursing in Aoteaoroa/New Zealand (A/NZ) that the
      concept developed and was subsequently integrated into nursing education.
      Cultural safety is based within a framework of biculturalism, and is congruent
      with the tenets of the nation's founding document, the Treaty of Waitangi.
      Clarification of the concept is offered, together with a review of the historical
      shift in nursing attitudes that has led to the emergence of "cultural safety" as
      a viable and valued component of nursing practice. The argument is made that
      cultural safety has allowed for a more reflective, critical understanding of the
      actions of nursing to develop. This includes recognition that nurses' attitudes
      and values have inevitably been influenced by social and political forces, and as
      such are in part reflective of those within the wider community. Comparison
      between the support given by nurses in the early 1900s to the theory of eugenics
      and the current acceptance of cultural safety is used to highlight this point. An
      examination of the literature identifies that ideological and conceptual changes
      have occurred in the approach of A/NZ nurses to issues with cultural implications
      for practice. A review of background factors relating to Maori health status and
      the Treaty of Waitangi is presented as a necessary context to the overall
      discussion. The discussion concludes with an acknowledgement that while the
      rhetoric of cultural safety is now part of nursing culture in New Zealand, there
      is no firm evidence to evaluate its impact in practice. Issues identified as
      impacting on the ability to assess/research a concept, such as cultural safety,
      are discussed. For cultural safety to become recognised as a credible (and
      indispensable) tool, it is necessary to further examine the "end-point" or
      "outcomes" of the process.

PMID- 14962346
TI  - Caregivers of persons with a brain tumor: a conceptual model.
AB  - Researchers have documented negative physical and emotional consequences for both
      family caregivers of persons with cancer as well as caregivers of persons with a
      neurologic disorder. However, there is a unique subset of caregivers who must
      provide care for someone who may suffer from both a short, terminal trajectory of
      disease, as well as neurological and neuropsychiatric sequelae - the caregiver of
      a person with a primary malignant brain tumor. The purpose of this article was to
      describe a conceptual framework for providing care for a person with a primary
      malignant brain tumor. The demands of this particular care situation are
      described, as well as potential resources available to the caregiver to meet
      those demands. Finally, the stress response that results from the balance between
      care demands and caregiver resources is illustrated. Development of a conceptual
      framework for this caregiving population is the first step in assisting nurses to
      identify factors that place caregivers of persons with a primary malignant brain
      tumor at risk for negative consequences, and to design interventions to improve
      caregiver health.

PMID- 14962347
TI  - Involving users with learning difficulties in health improvement: lessons from
      inclusive learning disability research.
AB  - In this paper the author considers the lessons to be drawn from what is termed
      "inclusive" learning disability research for user involvement around health
      improvement. Inclusive learning disability research refers to research where
      people with learning difficulties (intellectual disability) are involved as
      active participants, as opposed to passive subjects. There is by now a
      considerable body of such research, developed over the past 25 years. From the
      review, the author draws attention to areas which can inform practice in
      involvement of users in a way that adds value.

PMID- 14962348
TI  - The "Palliative Care Quality of Life Instrument (PQLI)" in terminal cancer
      patients.
AB  - BACKGROUND: This paper describes the development of a new quality of life
      instrument in advanced cancer patients receiving palliative care. METHODS: The
      Palliative Care Quality of Life Instrument incorporates six multi-item and one
      single-item scale. The questionnaire was completed at baseline and one-week
      after. The final sample consisted of 120 patients. RESULTS: The average time
      required to complete the questionnaire, in both time points, was approximately 8
      minutes. All multi-item scales met the minimal standards for reliability
      (Cronbach's alpha coefficient > or =.70) either before or during palliative
      treatment. Test-retest reliability in terms of Spearman-rho coefficient was also
      satisfactory (p < 0.05). Validity was demonstrated by inter-item correlations,
      comparisons with ECOG performance status, factor analysis, criterion-related
      validation, and correlations with the Assessment of Quality of Life in Palliative
      Care Instrument (AQEL), and the European Organisation for Research and Treatment
      of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30, version 3.0).
      CONCLUSION: The PQLI is a reliable and valid measure for the assessment of
      quality of life in patients with advanced stage cancer.

PMID- 14962350
TI  - Comparative Hepatology: A journal for all hepatologists with immediate Open
      Access to quality peer-reviewed research.

PMID- 14962349
TI  - Current problems of perinatal Chlamydia trachomatis infections.
AB  - Chlamydia trachomatis has been recognized as a pathogen of trachoma,
      nongonococcal urethritis, salpingitis, endocervicitis, pelvic inflammatory
      disease, inclusion conjunctivitis of neonates, follicular conjunctivitis of
      adults, infantile pneumonia and associated conditions. Chlamydial infections
      during pregnancy may also cause a variety of perinatal complications. Different
      antigenic strains of C. trachomatis from endocervical, nasopharyngeal and
      conjunctival origins have been associated with different clinical conditions.
      Control programs emphasizing early diagnosis, targeted screening, and effective
      treatment will lead to an eventual decline in the incidence of perinatal
      chlamydial infection. This review focuses on current problems of perinatal C.
      trachomatis infections in the aspects of microbiological and immunological
      pathogenesis.

PMID- 14962351
TI  - Fluoxetine: a review on evidence based medicine.
AB  - BACKGROUND: Fluoxetine was the first molecule of a new generation of
      antidepressants, the Selective Serotonin Re-uptake Inhibitors (SSRIs). It is
      recurrently the paradigm for the development of any new therapy in the treatment
      of depression. Many controlled studies and meta-analyses were performed on
      Fluoxetine, to improve the understanding of its real impact in the psychiatric
      area. The main objective of this review is to assess the quality and the results
      reported in the meta-analyses published on Fluoxetine. METHODS: Published
      articles on Medline, Embase and Cochrane databases reporting meta-analyses were
      used as data sources for this review.Articles found in the searches were reviewed
      by 2 independent authors, to assess if these were original meta-analyses. Only
      data belonging to the most recent and comprehensive meta-analytic studies were
      included in this review. RESULTS: Data, based on a group of 9087 patients, who
      were included in 87 different randomized clinical trials, confirms that
      fluoxetine is safe and effective in the treatment of depression from the first
      week of therapy. Fluoxetine's main advantage over previously available
      antidepressants (TCAs) was its favorable safety profile, that reduced the
      incidence of early drop-outs and improved patient's compliance, associated with a
      comparable efficacy on depressive symptoms. In these patients, Fluoxetine has
      proven to be more effective than placebo from the first week of
      therapy.Fluoxetine has shown to be safe and effective in the elderly population,
      as well as during pregnancy. Furthermore, it was not associated with an increased
      risk of suicide in the overall evaluation of controlled clinical trials.The meta
      analysis available on the use of Fluoxetine in the treatment of bulimia nervosa
      shows that the drug is as effective as other agents with fewer patients dropping
      out of treatment.Fluoxetine has demonstrated to be as effective as chlomipramine
      in the treatment of Obsessive-Compulsive-Disorder (OCD). CONCLUSION: Fluoxetine
      can be considered a drug successfully used in several diseases for its favorable
      safety/efficacy ratio. As the response rate of mentally ill patients is strictly
      related to each patient's personal characteristics, any new drug in this area,
      will have to be developed under these considerations.

PMID- 14962352
TI  - Menstrual disturbances a rare side-effect of bright-light therapy.

PMID- 14962353
TI  - Simultaneous depletion of tryptophan, tyrosine and phenylalanine as an
      experimental method to probe brain monoamine function in humans.
AB  - Brain monoamines are important regulators of affective and cognitive processes
      and are involved in the aetiology of a number of psychiatric disorders. While
      methods to probe serotonin and catecholamine function are established, limited
      methods are available to probe monoamine function as a whole in humans. In the
      current study, we examined if simultaneous depletion of monoamine precursors can
      be used as a possible probe of monoamine function. Ten healthy subjects were
      tested under two treatment conditions; balanced control (B) condition and
      combined monoamine depletion (CMD) condition. Monoamine precursor depletion was
      associated with significant reductions in plasma-free tryptophan (46%), tyrosine
      (74%) and phenylalanine (78%). Greater reductions were achieved for ratios of
      each precursor to other large neutral amino acids (LNAA); tryptophan/LNAA (86%),
      tyrosine/LNAA (94%) and phenylalanine/LNAA (94%). Findings suggest that
      simultaneous depletion of monoamine precursors can achieve significant plasma
      monoamine depletion in the range expected to affect brain monoamine function.

PMID- 14962354
TI  - Redox metabolism in malaria: from genes, through biochemistry and pathology, to
      drugs.

PMID- 14962355
TI  - Hemoglobin redox reactions and oxidative stress.
AB  - The role of hemoglobin in transporting oxygen is dependent on the reversible
      binding of oxygen to Fe(II) hemoglobin with molecular oxygen released at reduced
      oxygen pressures. The partially oxygenated hemoglobin formed with the release of
      oxygen from hemoglobin is susceptible to redox reactions where the functional
      Fe(II) heme is oxidized to Fe(III) and the substrate is reduced. In this article,
      we review two important redox reactions of hemoglobin and discuss the
      ramifications of these reactions. The reduction of oxygen to superoxide starts a
      cascade of oxidative reactions, which are a source for red cell-induced oxidative
      stress. The reduction of nitrite to nitric oxide produces a labile form of nitric
      oxide that can be a source for oxidative stress, but can also have important
      physiological functions.

PMID- 14962356
TI  - Sickle hemoglobin instability: a mechanism for malarial protection.
AB  - Heterozygosity for the mutant sickle hemoglobin confers protection from severe
      Plasmodium falciparum malaria. It is here proposed that this protection derives
      from the instability of sickle hemoglobin, which clusters red cell membrane
      protein band 3 and triggers accelerated removal by phagocytic cells. This
      explanation requires that sickle trait cells manifest greater hemoglobin
      instability than normal red cells, something that could derive from their content
      of sickle hemoglobin. The mechanism also implicates splenic function as a
      determinant of the protective effect.

PMID- 14962357
TI  - The role of oxidant injury in the pathophysiology of human thalassemias.
AB  - The anemia in beta-thalassemia major is caused by a combination of hemolysis and
      ineffective erythropoiesis, with the latter being more important. Studies of the
      underlying cause of the hemolysis have indicated that oxidant injury to
      circulating red blood cells (RBCs) was of critical importance, with evidence of
      oxidant damage to RBC membrane proteins 4.1 and band 3. Therefore, it seemed
      reasonable that oxidant damage to thalassemic erythroid precursors would cause
      their accelerated apoptosis and ineffective erythropoiesis. However, direct
      analysis showed that the apoptotic programs turned on in thalassemics were not
      those triggered by oxidative damage but were dependent on activation of FAS/FAS
      Ligand interaction. Thus, destruction of thalassemic erythroid precursors may
      involve different mechanisms from those that cause RBC hemolysis.

PMID- 14962358
TI  - Plasmodium falciparum thioredoxins and glutaredoxins as central players in redox
      metabolism.
AB  - Over the last few years, an increasing number of different functions have been
      ascribed to small redox-active proteins like thioredoxins (Trx) and glutaredoxins
      (Grx). These functions include redox regulation of transcription and translation,
      antioxidant defence, involvement in protein folding and cellular signalling, and
      reduction of ribonucleotide reductase. In the malarial parasite Plasmodium
      falciparum, a classical Trx and a typical Grx have been described as well as a
      number of Trx- and Grx-like proteins including monothiol glutaredoxins.
      Furthermore, plasmoredoxin, a redox-active protein related to Trx, has been
      characterized; plasmoredoxin is unique for malarial parasites, therefore having
      great potential as diagnostic tool. In this minireview, we summarize the current
      knowledge on members of the thioredoxin superfamily and their function in the
      malarial parasite P. falciparum.

PMID- 14962359
TI  - Thioredoxin reductase and glutathione synthesis in Plasmodium falciparum.
AB  - The malaria parasite Plasmodium falciparum is still a major threat to human
      health in the non-industrialised world mainly due to the increasing incidence of
      drug resistance. Therefore, there is an urgent need to identify and validate new
      potential drug targets in the parasite's metabolism that are suitable for the
      design of new anti-malarial drugs. It is known that infection with P. falciparum
      leads to increased oxidative stress in red blood cells, implying that the
      parasite requires efficient antioxidant and redox systems to prevent damage
      caused by reactive oxygen species. In recent years, it has been shown that P.
      falciparum possess functional thioredoxin and glutathione systems. Using genetic
      and chemical tools, it was demonstrated that thioredoxin reductase, the first
      step of the thioredoxin redox cycle, and gamma-glutamylcysteine synthetase (gamma
      GCS), the rate-limiting step of glutathione synthesis, are essential for parasite
      survival. Indeed, the mRNA levels of gamma-GCS are elevated in parasites that are
      oxidatively stressed, indicating that glutathione plays an important antioxidant
      role in P. falciparum. In addition to this antioxidant function, glutathione is
      important for detoxification processes and is possibly involved in the
      development of resistance against drugs such as chloroquine.

PMID- 14962360
TI  - Thiol-dependent peroxidases care little about homology-based assignments of
      function.
AB  - Thiol-dependent peroxidase systems are reviewed with special emphasis on their
      potential use as drug targets. The basic catalytic mechanism of the two major
      thiol-peroxidase families, the glutathione peroxidases and the peroxiredoxins,
      are reasonably well understood. Sequence-based predictions of substrate
      specificities are still unsatisfactory. GPx-type enzymes are not generally
      specific for GSH but may specifically react with CXXC motifs as present in
      thioredoxins or tryparedoxins. Inversely, the peroxiredoxin family that was
      believed to be specific for CXXC-type proteins, also comprises glutathione
      peroxidases. Since structure-based predictions of function are also limited by
      small data bases, the increasing number of sequences emerging from genome
      projects require enzymatic characterization and genetic proof of relevance before
      they can be classified as drug targets.

PMID- 14962361
TI  - Superoxide dismutase in Plasmodium: a current survey.

PMID- 14962362
TI  - Iron chelators as drugs against malaria pose a potential risk.

PMID- 14962363
TI  - Methylene blue as an antimalarial agent.
AB  - Methylene blue has intrinsic antimalarial activity and it can act as a
      chloroquine sensitizer. In addition, methylene blue must be considered for
      preventing methemoglobinemia, a serious complication of malarial anemia. As an
      antiparasitic agent, methylene blue is pleiotropic: it interferes with hemoglobin
      and heme metabolism in digestive organelles, and it is a selective inhibitor of
      Plasmodium falciparum glutathione reductase. The latter effect results in
      glutathione depletion which sensitizes the parasite for chloroquine action. At
      the Centre de Recherche en Sante de Nouna in Burkina Faso, we study the
      combination of chloroquine with methylene blue (BlueCQ) as a possible medication
      for malaria in endemic regions. A pilot study with glucose-6-phosphate
      dehydrogenase-sufficient adult patients has been conducted recently.

PMID- 14962364
TI  - Glutathione is involved in the antimalarial action of chloroquine and its
      modulation affects drug sensitivity of human and murine species of Plasmodium.
AB  - Ferriprotoporphyrin IX (FP) is released inside the food vacuole of the malaria
      parasite during the digestion of host cell hemoglobin. FP is detoxified by its
      biomineralization to hemozoin. This process is effectively inhibited by
      chloroquine (CQ) and amodiaquine (AQ). Undegraded FP accumulates in the membrane
      fraction and inhibits enzymes of infected cells in parallel with parasite
      killing. FP is demonstrably degraded by reduced glutathione (GSH) in a radical
      mediated mechanism. This degradation is inhibited by CQ and AQ in a competitive
      manner, thus explaining the ability of increased GSH levels in Plasmodium
      falciparum-infected cells to increase resistance to CQ and vice versa, and to
      render Plasmodium berghei that were selected for CQ resistance in vivo sensitive
      to the CQ when glutathione synthesis is inhibited. Some over-the-counter drugs
      that are known to reduce GSH in body tissues when used in excess were found to
      enhance the antimalarial action of CQ and AQ in mice infected either with P.
      berghei or Plasmodium vinckei. In contrast, N-acetyl-cysteine which is expected
      to increase the cellular levels of GSH, antagonized the action of CQ. These
      results suggest that some over-the-counter drugs can be used in combination with
      some antimalarials to which the parasite has become resistant.

PMID- 14962365
TI  - Double-drug development against antioxidant enzymes from Plasmodium falciparum.
AB  - New drugs against malaria are urgently and continuously needed. Plasmodium
      parasites are exposed to higher fluxes of reactive oxygen species and need high
      activities of intracellular antioxidant systems. A most important antioxidative
      system consists of (di)thiols which are recycled by disulfide reductases (DR),
      namely both glutathione reductases (GR) of the malarial parasite Plasmodium
      falciparum and man, and the thioredoxin reductase (TrxR) of P. falciparum. The
      aim of our interdisciplinary research is to substantiate DR inhibitors as
      antimalarial agents. Such compounds are active per se but, in addition, they can
      reverse thiol-based resistance against other drugs in parasites. Reversal of drug
      resistance by DR inhibitors is currently investigated for the commonly used
      antimalarial drug chloroquine (CQ). Our recent strategy is based on the synthesis
      of inhibitors of the glutathione reductases from parasite and host erythrocyte.
      With the expectation of a synergistic or additive effect, double-headed prodrugs
      were designed to be directed against two different and essential functions of the
      malarial parasite P. falciparum, namely glutathione regeneration and heme
      detoxification. The prodrugs were prepared by linking bioreversibly a GR
      inhibitor to a 4-aminoquinoline moiety which is known to concentrate in the
      acidic food vacuole of parasites. Drug-enzyme interaction was correlated with
      antiparasitic action in vitro on strains resistant towards CQ and in vivo in
      Plasmodium berghei-infected mice as well as absence of cytotoxicity towards human
      cells. Because TrxR of P. falciparum was recently shown to be responsible for the
      residual glutathione disulfide-reducing capacity observed after GR inhibition in
      P. falciparum, future development of antimalarial drug-candidates that act by
      perturbing the redox equilibrium of parasites is based on the design of new
      double-drugs based on TrxR inhibitors as potential antimalarial drug candidates.

PMID- 14962366
TI  - Mechanisms of in situ activation for peroxidic antimalarials.
AB  - This review describes mechanisms of action of artemisinin-related antimalarials,
      emphasizing the site and target of activation, pathways of generating reactive
      species, and possible targets of free radicals with implications for antimalarial
      peroxide drug design. It also presents a useful link between the mode of action
      of artemisinin and that of chloroquine, and highlights redox cycles involved in
      the interaction between the drug and vital biomolecules.

PMID- 14962367
TI  - Regulation of nitrogen monoxide production in human malaria.
AB  - The production of nitrogen monoxide (NO(*)) contributes to defence mechanisms of
      the immune system to fight infectious agents like bacteria and protozoa. The
      respective gene producing the NO(*) has to be carefully regulated so that an
      overwhelming response kills the pathogen but does not harm the host. A strong
      increase in the NO(*) production for efficient anti-microbial activity is
      achieved by the transcriptional up-regulation of the nitric oxide synthase 2 gene
      (NOS2 or inducible nitric oxide synthase, iNOS), which is regulated by a number
      of transcription factors that are vital in the regulation of many genes involved
      in the immune response. Binding sites for members of the nuclear factor-kappaB
      (NF-kappaB) and activator protein 1 (AP1) families have been detected and seem to
      fulfil their function in vitro. Genetic variants of the iNOS genes have been
      identified that are linked to NO(*) production and to the outcome of malaria in
      humans.

PMID- 14962368
TI  - Oxidative stress and rheology in severe malaria.
AB  - There is mounting evidence that the release of haemozoin (beta-haematin), which
      is produced in large amounts during malaria infection and is released into the
      circulation during schizont rupture, is associated with damage to cell membranes
      through an oxidative mechanism. The red blood cell membrane is thus oxidised,
      causing rigidity of the cell. This can contribute to the pathophysiology of
      severe malaria, since red blood cells will have to deform considerably in order
      to squeeze through the microcirculation, the patency of which is disturbed by
      sequestered red blood cells containing the mature forms of the parasite. Rigidity
      of red blood cells forms a new target for intervention. Since this seems to be
      caused by oxidative damage to the red blood cell membrane, the anti-oxidant N
      acetylcysteine is a promising candidate for adjunctive treatment in severe
      malaria, which still has a mortality rate as high as 20%.

PMID- 14962369
TI  - Sequestration: causes and consequences.
AB  - Adhesion of Plasmodium falciparum-infected erythrocytes to endothelial cells and
      to syncytiotrophoblasts lining the placenta is a key feature of malaria
      pathogenesis. P. falciparum erythrocyte membrane protein 1, a family of variable
      proteins, mediates adhesion to CD36 and intercellular adhesion molecule 1 in the
      systemic vasculature, and to chondroitin sulphate A and hyaluronic acid in the
      placenta. Recent studies of the pathology of fatal cerebral malaria and of
      placental malaria that follow such sequestration suggest that coagulation
      disturbances may have a greater role in pathogenesis than previously realized,
      and that monocyte infiltrates in response to malaria may initiate some of these
      changes. Chemokines such as macrophage inflammatory protein 1 alpha and beta and
      monocyte chemoattractant protein 1 may play a key role in attracting monocytes to
      the placenta and other organs, but the stimulus to chemokine secretion is not
      presently known.

PMID- 14962370
TI  - Mechanisms of band 3 oxidation and clustering in the phagocytosis of Plasmodium
      falciparum-infected erythrocytes.
AB  - Erythrocytes (RBCs) opsonized by IgG and complement are prevalently recognized
      and phagocytosed by complement receptor CR1. This mechanism, effective in
      senescent and damaged RBCs seems to be operative in ring-parasitized RBCs, since
      infection by Plasmodium falciparum induces stage-dependent binding of auto
      antibodies and activated C3 to the RBC membrane. Later, parasite forms are also
      recognized by non-opsonic receptors, such as scavenger receptor CD36. Malaria
      parasites induce the oxidative formation of hemichromes which are the trigger for
      the auto-antigen development. Band 3 protein is the most plausible candidate of
      the RBC auto-antigen, induced by hemichromes. Auto-antigens isolated from
      trophozoites were found only in a high-molecular-weight protein aggregates not
      present in the normal RBC. The immunocomplex was purified by protein-A affinity
      chromatography, purified proteins digested by trypsin and analyzed by MALDI-TOF.
      Peptide mapping showed that the main antigen consisted of band 3 protein
      aggregates that also contained hemichromes, IgGs, complement factor 3 (C3), and
      traces of spectrin and glycophorin but no parasite proteins. Two cysteines
      located in the band 3 cytoplasmic domain were found to be particularly reactive
      to oxidants and mediated band 3 covalent dimerization via disulfide bonds. Thus,
      parasites promote oxidative alterations in the membrane of the host which lead to
      exposure of antigenic sites recognized by anti-band 3 auto-antibodies. Formation
      of band 3 clusters appears to be mediated by cytoplasmic binding of hemichromes
      and also by direct band 3 oxidation, whereby clustered, oxidized and antigenic
      band 3 was underglycosylated.

PMID- 14962371
TI  - Haemoglobinopathies and resistance to malaria.
AB  - The haemoglobinopathies have a celebrated role in the study of human genetics as
      the first examples of balanced polymorphisms described in human populations. Over
      the last 50 years, considerable evidence has been provided to show that these
      traits do confer protection from malaria. More recently, the underlying
      mechanisms of protection have been examined. This short review summarizes these
      studies and where possible shows how the putative mechanisms of protection may be
      linked to redox processes.

PMID- 14962372
TI  - The Haldane malaria hypothesis: facts, artifacts, and a prophecy.
AB  - Heterozygous thalassemia and sickle cell disease produce mild hematological
      symptoms but provide protection against malaria mortality and severe malaria
      symptoms. Two explanations for resistance are considered in the literature -
      impaired growth of the parasite or enhanced removal by the host immune cells. A
      critical overview of studies that connect malaria resistance with impaired intra
      erythrocytic growth is presented. All studies are fraught with two kinds of bias.
      The first one resides in the impossibility of reproducing the in vivo situation
      in the simplified model in vitro. The second stems from the generalized use of
      RPMI 1640 culture medium. RPMI 1640 has critically low levels of several amino
      acids; is devoid of hypoxanthine (essential for parasite growth) and adenine; and
      is low in reduced glutathione. Analysis of representative studies indicates that
      impaired parasite growth in heterozygous red blood cells (RBCs) may derive from
      nutrient limitations and, therefore, possibly be of artefactual origin. This
      conclusion seems plausible because studies were performed with RPMI 1640 medium
      at relatively high hematocrit and for prolonged periods of time. Mutations
      considered are particularly sensitive to nutrient deprivation because they have
      higher metabolic demands due to permanent oxidant stress related to unpaired
      globin chains, sickle hemoglobin and high levels of membrane-free iron. In
      addition, non-parasitized AS- and thalassemic-RBCs are dehydrated and microcytic.
      Thus, the number of metabolically active elements per unit of blood volume is
      remarkably larger in mutant RBCs compared to normocytes. The latter point may
      represent a confirmation of Haldane's prophetic statement: 'The corpuscles of the
      anaemic heterozygotes are smaller than normal, and more resistant to hypotonic
      solutions. It is at least conceivable that they are also more resistant to
      attacks by the sporozoa which cause malaria.'

PMID- 14962373
TI  - PlasmoDB: exploring genomics and post-genomics data of the malaria parasite,
      Plasmodium falciparum.
AB  - The recent completion of the genome sequence of Plasmodium falciparum 3D7
      provides the foundation for genome-wide analysis of the parasite. In addition to
      DNA and gene sequence data, postgenomic methods including microarray-based
      transcript profiling and high-throughput proteomics are now accessible to
      Plasmodium researchers. The Plasmodium Genome database (<http://PlasmoDB.org>)
      was developed to provide rapid and convenient access to the terabytes of genomic
      scale data now being generated around the world. All data are available in a
      relational framework, permitting convenient downloading, browsing, and analysis.
      Combinatorial use of data analysis tools enables powerful data mining queries,
      such as combining gene and protein expression data to monitor changes through
      various life-cycle stages. Functional predictions can be used to explore
      potential targets for antimalarial drug development. This report outlines the use
      of PlasmoDB to examine redox-active functions in Plasmodium.

PMID- 14962374
TI  - Collagen fibril orientation and corneal curvature.

PMID- 14962375
TI  - Accessing information on the conformational flexibility of molecular machines.

PMID- 14962376
TI  - Gauging length: recognition of small interfering RNAs.

PMID- 14962377
TI  - The 447-52D antibody: hitting HIV-1 where its armor is thickest.

PMID- 14962378
TI  - Protein binding and disruption by Clp/Hsp100 chaperones.
AB  - Clp/Hsp100 chaperones work with other cellular chaperones and proteases to
      control the quality and amounts of many intracellular proteins. They employ an
      ATP-dependent protein unfoldase activity to solubilize protein aggregates or to
      target specific classes of proteins for degradation. The structural complexity of
      Clp/Hsp100 proteins combined with the complexity of the interactions with their
      macromolecular substrates presents a considerable challenge to understanding the
      mechanisms by which they recognize and unfold substrates and deliver them to
      downstream enzymes. Fortunately, high-resolution structural data is now available
      for several of the chaperones and their functional partners, which together with
      mutational data on the chaperones and their substrates has provided a glimmer of
      light at the end of the Clp/Hsp100 tunnel.

PMID- 14962379
TI  - Experimental verification of conformational variation of human fatty acid
      synthase as predicted by normal mode analysis.
AB  - Fatty acid synthase (FAS) is a 550 kDa homodimeric enzyme with multiple
      functional and structural domains. Normal mode analysis of a previously
      determined 19 A structure of FAS suggested that this enzyme might assume
      different conformational states with several distinct hinge movements. We have
      used a simultaneous multiple-model refinement method to search for the presence
      of the structural conformers from the electron images of FAS. We have
      demonstrated that the resulting models observed in the electron images are
      consistent with the predicted conformational changes. This technique demonstrates
      the potential of the combination of normal mode analysis with multiple model
      refinement to elucidate the multiple conformations of flexible proteins. Since
      each of these structures is based on a more homogeneous particle set, this
      technique has the potential, provided that sufficient references are used, to
      improve the resolution of the final reconstructions of single particles from
      electron cryomicroscopy.

PMID- 14962380
TI  - Structural rationale for the broad neutralization of HIV-1 by human monoclonal
      antibody 447-52D.
AB  - 447-52D is a human monoclonal antibody isolated from a heterohybridoma derived
      from an HIV-1-infected individual. This antibody recognizes the hypervariable
      gp120 V3 loop, and neutralizes both X4 and R5 primary isolates, making it one of
      the most effective anti-V3 antibodies characterized to date. The crystal
      structure of the 447-52D Fab in complex with a 16-mer V3 peptide at 2.5 A
      resolution reveals that the peptide beta hairpin forms a three-stranded mixed
      beta sheet with complementarity determining region (CDR) H3, with most of the V3
      side chains exposed to solvent. Sequence specificity is conferred through
      interaction of the type-II turn (residues GPGR) at the apex of the V3 hairpin
      with the base of CDR H3. This novel mode of peptide-antibody recognition enables
      the antibody to bind to many different V3 sequences where only the GPxR core
      epitope is absolutely required.

PMID- 14962381
TI  - DNA binding and degradation by the HNH protein ColE7.
AB  - The bacterial toxin ColE7 bears an HNH motif which has been identified in
      hundreds of prokaryotic and eukaryotic endonucleases, involved in DNA homing,
      restriction, repair, or chromosome degradation. The crystal structure of the
      nuclease domain of ColE7 in complex with a duplex DNA has been determined at 2.5
      A resolution. The HNH motif is bound at the minor groove primarily to DNA
      phosphate groups at and beyond the 3' side of the scissile phosphate, with little
      interaction with ribose groups and bases. This result provides a structural basis
      for sugar- and sequence-independent DNA recognition and the inhibition mechanism
      by inhibitor Im7, which blocks the substrate binding site but not the active
      site. Structural comparison shows that two families of endonucleases bind and
      bend DNA in a similar way to that of the HNH ColE7, indicating that endonucleases
      containing a "betabetaalpha-metal" fold of active site possess a universal mode
      for protein-DNA interactions.

PMID- 14962382
TI  - Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK1.
AB  - LY333531, BIM-1, BIM-2, BIM-3, and BIM-8 are bisindolyl maleimide-based,
      nanomolar protein kinase C inhibitors. LY333531, a PKCbeta-specific inhibitor, is
      in clinical trials against diabetes and cardiac ventricular hypertrophy
      complications. Specificity analysis with a panel of 29 protein kinases reveals
      that these bisindolyl maleimide inhibitors also inhibit PDK1, a key kinase from
      the insulin signaling pathway, albeit in the lower microM range. To understand
      the molecular basis of inhibition, the PDK1 kinase domain was cocrystallized with
      these bisindolyl maleimide inhibitors. The inhibitor complexes represent the
      first structural description of this class of compounds, revealing their unusual
      nonplanar conformation within the ATP binding site and also explaining the higher
      inhibitory potential of LY33331 compared to the BIM compounds toward PDK1. A
      combination of site-directed mutagenesis and essential dynamics analysis gives
      further insight into PDK1 and also PKC inhibition by these compounds, and may aid
      inhibitor design.

PMID- 14962383
TI  - Visualizing the RNA molecule in the bacterially expressed vesicular stomatitis
      virus nucleoprotein-RNA complex.
AB  - Packaging of the RNA molecule in viruses is important for the preservation and
      expression of viral genomic information. The vesicular stomatitis virus (VSV)
      nucleoproteins are kept associated with its negative-strand RNA during the mRNA
      synthesis and replication, in contrast to the tobacco mosaic virus whose
      nucleoproteins are released from RNA. It has been a puzzle how the VSV RNA is
      packaged to meet the contradicting requirements of protection and the
      accessibility to the polymerase. We report an 18 A resolution structure of the
      recombinant nucleoprotein-RNA complex determined by single-particle electron
      microscopy. In the 3D density map, a ring of density is resolved on the inner
      surface and the density is proposed to be the RNA. The RNA is located on the
      inner surface of the decameric complex near the top end. This is dramatically
      different from the RNA packaging in TMV, but consistent with previously published
      biochemical findings.

PMID- 14962384
TI  - The structure of the stemloop D subdomain of coxsackievirus B3 cloverleaf RNA and
      its interaction with the proteinase 3C.
AB  - Stemloop D (SLD) of the 5' cloverleaf RNA is the cognate ligand of the
      coxsackievirus B3 (CVB3) 3C proteinase (3Cpro). Both are indispensable components
      of the viral replication initiation complex. SLD is a structurally autonomous
      subunit of the 5' cloverleaf. The SLD structure was solved by NMR spectroscopy to
      an rms deviation of 0.66 A (all heavy atoms). SLD contains a novel triple
      pyrimidine mismatch motif with a central Watson-Crick type C:U pair. SLD is
      capped by an apical uCACGg tetraloop adopting a structure highly similar to
      stable cUNCGg tetraloops. Binding of CVB3 3Cpro induces changes in NMR spectra
      for nucleotides adjacent to the triple pyrimidine mismatch and of the tetraloop
      implying them as sites of specific SLD:3Cpro interaction. The binding of 3Cpro to
      SLD requires the integrity of those structural elements, strongly suggesting that
      3Cpro recognizes a structural motif instead of a specific sequence.

PMID- 14962385
TI  - X-ray scattering used to map the preferred collagen orientation in the human
      cornea and limbus.
AB  - Many properties of connective tissues are governed by the organization of the
      constituent collagen. For example, the organization of collagen in the cornea and
      the limbus, where the cornea and sclera meet, is an important determinant of
      corneal curvature and hence of the eye's focusing power. We have used synchrotron
      X-ray scattering to map the orientation of the collagen fibrils throughout the
      human cornea, limbus, and adjacent sclera. We demonstrate a preferred orientation
      of collagen in the vertical and horizontal directions that is maintained to
      within about 1 mm from the limbus, where a circular or tangential disposition of
      fibrils occurs. The data are also used to map the relative distribution of both
      the total and the preferentially aligned collagen in different parts of the
      tissue, revealing considerable anisotropy. The detailed structural information
      provided is an important step toward understanding the shape and the mechanical
      properties of the tissue.

PMID- 14962386
TI  - Crystal structures of Weissella viridescens FemX and its complex with UDP-MurNAc
      pentapeptide: insights into FemABX family substrates recognition.
AB  - Members of the FemABX protein family are novel therapeutic targets, as they are
      involved in the synthesis of the bacterial cell wall. They catalyze the addition
      of amino acid(s) on the peptidoglycan precursor using aminoacylated tRNA as a
      substrate. We report here the high-resolution structure of Weissella viridescens
      L-alanine transferase FemX and its complex with the UDP-MurNAc-pentapeptide. This
      is the first structure example of a FemABX family member that does not possess a
      coiled-coil domain. FemX consists of two structurally equivalent domains,
      separated by a cleft containing the binding site of the UDP-MurNAc-pentapeptide
      and a long channel that traverses one of the two domains. Our structural studies
      bring new insights into the evolution of the FemABX and the related GNAT
      superfamilies, shed light on the recognition site of the aminoacylated tRNA in
      Fem proteins, and allowed manual docking of the acceptor end of the alanyl
      tRNAAla.

PMID- 14962387
TI  - Mass spectrometry of Escherichia coli RNA polymerase: interactions of the core
      enzyme with sigma70 and Rsd protein.
AB  - The E. coli RNA polymerase core enzyme is a multisubunit complex of 388,981 Da.
      To initiate transcription at promoters, the core enzyme associates with a sigma
      subunit to form holo RNA polymerase. Here we have used nanoflow electrospray mass
      spectrometry, coupled with tandem mass spectrometry, to probe the interaction of
      the RNA polymerase core enzyme with the most abundant sigma factor, sigma70. The
      results show remarkably well-resolved spectra for both the core and holo RNA
      polymerases. The regulator of sigma70, Rsd protein, has previously been
      identified as a protein that binds to free sigma70. We show that Rsd also
      interacts with core enzyme. In addition, by adding increasing amounts of Rsd, we
      show that sigma70 is displaced from holo RNA polymerase, resulting in complexes
      of Rsd with core and sigma70. The results argue for a model in which Rsd not only
      sequesters sigma70, but is also an effector of core RNA polymerase.

PMID- 14962388
TI  - Crystal structure of Mycoplasma arthritidis mitogen complexed with HLA-DR1
      reveals a novel superantigen fold and a dimerized superantigen-MHC complex.
AB  - Mycoplasma arthritidis-derived mitogen (MAM) is a superantigen that can activate
      large fractions of T cells bearing particular TCR Vbeta elements. Here we report
      the crystal structure of MAM complexed with a major histocompatibility complex
      (MHC) antigen, HLA-DR1, loaded with haemagglutinin peptide 306-318 (HA). The
      structure reveals that MAM has a novel fold composed of two alpha-helical
      domains. This fold is entirely different from that of the pyrogenic
      superantigens, consisting of a beta-grasped motif and a beta barrel. In the
      complex, the N-terminal domain of MAM binds orthogonally to the MHC alpha1 domain
      and the bound HA peptide, and to a lesser extent to the MHC beta1 domain. Two MAM
      molecules form an asymmetric dimer and cross-link two MHC antigens to form a
      plausible, dimerized MAM-MHC complex. These data provide the first
      crystallographic evidence that superantigens can dimerize MHC molecules. Based on
      our structure, a model of the TCR2MAM2MHC2 complex is proposed.

PMID- 14962389
TI  - The glutaredoxin -C-P-Y-C- motif: influence of peripheral residues.
AB  - The variety of cellular functions performed by proteins of the thioredoxin
      superfamily is made possible by the wide range of redox potential associated with
      their active site -Cys-X-X-Cys- motif. The determinants of these differences in
      redox potential are of considerable interest but are not well understood. E. coli
      Glutaredoxin 1 (Grx1) and 3 (Grx3) are important model systems with different
      redox properties, despite sharing the same -Cys-Pro-Tyr-Cys- motif, very similar
      overall structures, and 33% sequence identity. Very long molecular dynamics
      simulations (0.25 micros total) and electrostatic calculations provide a revised
      view of the reduced Grx1 active site, which now can be reconciled with
      biochemical and functional data. Comparison of this new model to Grx3 uncovers
      differences in the structure, dynamics, and electrostatics of these active sites.
      The influence of peripheral residues on the properties of the -Cys-X-X-Cys- motif
      is illustrated specifically with the effect of a Lys to Arg substitution.

PMID- 14962390
TI  - The structure of Yersinia pestis V-antigen, an essential virulence factor and
      mediator of immunity against plague.
AB  - The LcrV protein (V-antigen) is a multifunctional virulence factor in Yersinia
      pestis, the causative agent of plague. LcrV regulates the translocation of
      cytotoxic effector proteins from the bacterium into the cytosol of mammalian
      cells via a type III secretion system, possesses antihost activities of its own,
      and is also an active and passive mediator of resistance to disease. Although a
      crystal structure of this protein has been actively sought for better
      understanding of its role in pathogenesis, the wild-type LcrV was found to be
      recalcitrant to crystallization. We employed a surface entropy reduction
      mutagenesis strategy to obtain crystals of LcrV that diffract to 2.2 A and
      determined its structure. The refined model reveals a dumbbell-like molecule with
      a novel fold that includes an unexpected coiled-coil motif, and provides a
      detailed three-dimensional roadmap for exploring structure-function relationships
      in this essential virulence determinant.

PMID- 14962391
TI  - The structural basis for RNA specificity and Ca2+ inhibition of an RNA-dependent
      RNA polymerase.
AB  - The RNA-dependent RNA polymerase of bacteriophage phi6 transcribes mRNA from the
      three segments of the dsRNA viral genome. We have cocrystallized RNA
      oligonucleotides with the polymerase, revealing the mode of binding of RNA
      templates. This binding is somewhat different from that previously seen for DNA
      oligomers, leading to additional RNA-protein hydrogen bonds, consistent with a
      preference for RNA. Activation of the RNA/polymerase complex by the addition of
      substrate and Mg2+ initiates a single round of reaction within the crystal to
      form a dead-end complex that partially collapses within the enzyme active site.
      By replacing Mg2+ with Ca2+, we have been able to capture the inhibited complex
      which shows distortion that explains the structural basis for the inhibition of
      such polymerases by Ca2+.

PMID- 14962392
TI  - Structure-function analysis of human [corrected] phosphatidylinositol transfer
      protein alpha bound to phosphatidylinositol.
AB  - Phosphatidylinositol transfer protein alpha (PITPalpha) selectively transports
      and promotes exchange of phosphatidylinositol (PI) and phosphatidylcholine (PC)
      between lipid bilayers. In higher eukaryotes PITPalpha is required for cellular
      functions such as phospholipase C-mediated signaling, regulated exocytosis, and
      secretory vesicle formation. We have determined the crystal structure of human
      PITPalpha bound to its physiological ligand, PI, at 2.95 A resolution. The
      structure identifies the critical side chains within the lipid-headgroup binding
      pocket that define the exquisite specificity for PI. Mutational analysis of the
      PI binding pocket is in good agreement with the structural data and allows
      manipulation of functional properties of PITPalpha. Surprisingly, there are no
      major conformational differences between PI- and PC-loaded PITPalpha, despite
      previous predictions. In the crystal, PITPalpha-PI is dimeric, with two identical
      dimers in the asymmetric unit. The dimer interface masks precisely the sequence
      we identify as contributing to PITPalpha membrane interaction. Our structure
      represents a soluble, transport-competent form of PI-loaded PITPalpha.

PMID- 14962393
TI  - Structure and mechanism of RNA ligase.
AB  - T4 RNA ligase 2 (Rnl2) exemplifies an RNA ligase family that includes the RNA
      editing ligases (RELs) of Trypanosoma and Leishmania. The Rnl2/REL enzymes are
      defined by essential signature residues and a unique C-terminal domain, which we
      show is essential for sealing of 3'-OH and 5'-PO4 RNA ends by Rnl2, but not for
      ligase adenylation or phosphodiester bond formation at a preadenylated AppRNA
      end. The N-terminal segment Rnl2(1-249) of the 334 aa Rnl2 protein comprises an
      autonomous adenylyltransferase/AppRNA ligase domain. We report the 1.9 A crystal
      structure of the ligase domain with AMP bound at the active site, which reveals a
      shared fold, catalytic mechanism, and evolutionary history for RNA ligases, DNA
      ligases, and mRNA capping enzymes.

PMID- 14962394
TI  - The nsp9 replicase protein of SARS-coronavirus, structure and functional
      insights.
AB  - As part of a high-throughput structural analysis of SARS-coronavirus (SARS-CoV)
      proteins, we have solved the structure of the non-structural protein 9 (nsp9).
      This protein, encoded by ORF1a, has no designated function but is most likely
      involved with viral RNA synthesis. The protein comprises a single beta-barrel
      with a fold previously unseen in single domain proteins. The fold superficially
      resembles an OB-fold with a C-terminal extension and is related to both of the
      two subdomains of the SARS-CoV 3C-like protease (which belongs to the serine
      protease superfamily). nsp9 has, presumably, evolved from a protease. The crystal
      structure suggests that the protein is dimeric. This is confirmed by analytical
      ultracentrifugation and dynamic light scattering. We show that nsp9 binds RNA and
      interacts with nsp8, activities that may be essential for its function(s).

PMID- 14962395
TI  - Exorcizing the homunculus, phase two: editors' introduction.

PMID- 14962396
TI  - Executive control emerging from dynamic interactions between brain systems
      mediating language, working memory and attentional processes.
AB  - In this theoretical paper, we review findings from a series of recent behavioral
      and functional neuroimaging studies of working memory and executive control which
      provide evidence for the following theses: 1. Working memory in humans is
      represented by two brain systems which differ from each other with respect to
      their functional-neuroanatomical organization and probably also with respect to
      their evolutionary origin. 2. One of these brain systems relies on prefronto
      parietal and prefronto-temporal cortical networks that presumably also mediate
      attentional selection by the top-down modulation of domain-specific sensory
      association areas towards behaviorally relevant information. 3. The other system
      is implemented by mainly left-hemispheric premotor and parietal brain regions
      which to a greater part also underlie language functions and which may also be
      involved in the retrieval and maintenance of verbal goal representations during
      advance preparation for task switches. 4. Context-sensitive behavioral adaptation
      is supported by a complementary mechanism for the detection of conflicts and for
      the triggering of cognitive control processes that relies on parts of the medial
      frontal cortex. Based on these empirical results reported in the literature we
      propose a neurocognitive model of executive control according to which the human
      ability to flexibly adapt to changing behavioral requirements, i.e. executive
      control, depends on dynamic and context-sensitive interactions between these
      brain systems.

PMID- 14962397
TI  - Inner speech as a retrieval aid for task goals: the effects of cue type and
      articulatory suppression in the random task cuing paradigm.
AB  - Articulatory suppression has been shown to increase switch costs in the list
      paradigm (e.g., [J. Exp. Psychol.: General 130 (2001) 641, J Memory Language 48
      (2003) 148]). The present dual-task study examined whether this effect
      generalizes to the random task cuing paradigm. Participants performed color or
      shape judgments according to explicit word cues (COLOR or SHAPE) or less
      transparent letter cues ( C for the color task and S for the shape task). In the
      word cue condition, the switch cost was equivalent for the articulatory
      suppression and the control (no dual-task) conditions, but, in the letter cue
      condition, the switch cost was significantly greater for the articulatory
      suppression condition than for the control condition. These results suggest that
      inner speech may be recruited as a tool for retrieving and activating the
      relevant task goal when the task cue is not transparent and hence imposes
      nonnegligible retrieval demand.

PMID- 14962398
TI  - Age differences in executive functioning across the lifespan: the role of
      verbalization in task preparation.
AB  - Age-related changes in executive functioning across the lifespan were assessed in
      children (mean age=9.4 years), younger adults (mean age=21.5 years), and older
      adults (mean age=65.3 years). Executive functioning was investigated with a task
      switching paradigm that permits the separation of two control components: to
      select and to switch between task sets. The specific aims of this study were (a)
      to determine developmental functions in both control components across the
      lifespan; and (b) to examine whether age-related changes in these components are
      influenced by verbal prompts during task preparation. The results revealed an
      inverted u-shaped developmental function for the ability to select between task
      sets but not for the ability to switch between task sets. In contrast to younger
      adults and children, older adults generally benefited from verbalizations during
      task preparation. Children, but not older adults, showed a facilitation of task
      execution when verbal prompts were task-compatible. Conversely, older adults, but
      not children, showed stronger interference when verbal prompts are task
      incompatible. Our findings suggest that inner speech in an important modulator of
      developmental changes in executive functioning across the lifespan.

PMID- 14962399
TI  - Executive function across the life span.
AB  - The development and determinants of executive function (EF) were studied in
      children (mean age=8.8 years), young adults ( M= 22.3 years), and elderly adults
      (M = 71.1 years). EF was indexed by perseverative responding on two bidimensional
      sorting tasks (Visually Cued Color-Shape task and Auditorily Cued Number-Numeral
      task), and age-related changes in EF were considered in relation to estimates of
      conscious vs. unconscious memory that were obtained using the process
      dissociation procedure (PDP). Results revealed the rise and fall of EF across the
      life span, with significant quadratic trends found for performance on both
      sorting tasks and for the conscious recollection component (C) of the PDP task.
      Regression analyses indicated that PDP estimates of conscious memory accounted
      for variation in performance on the visual sorting task, but not on the auditory
      sorting task. The findings are discussed in terms of their implications for
      hierarchical models of EF and its development.

PMID- 14962400
TI  - Development of the acquisition and control of action-effect associations.
AB  - Voluntary action is anticipatory and, hence, must depend on associations between
      actions and their perceivable effects. We studied the acquisition of action
      effect associations in 4-5-vs. 7-year-old children. Children carried out key
      pressing actions that were arranged to produce particular auditory effects. In a
      subsequent test phase, children were to press keys in response to the previous
      effect sounds, with the sound-key mapping being either consistent or inconsistent
      with previous key-sound practice. As the processes underlying voluntary action
      controls are known to significantly improve between 4 and 7 years of age, it was
      expected that younger children were more prone to automatic effects of acquired
      sound-key associations. This hypothesis was confirmed, but reaction times and
      accuracy measures showed different and dissociable patterns. Four-year-olds but
      not 7-year-olds were more likely to commit an error--i.e., to perform a sound
      compatible rather than the correct action--if the sound-key mapping was
      inconsistent with previous practice. This effect strongly depended on previous
      practice, suggesting that it reflects long-term learning. In contrast, reaction
      time effects of mapping consistency did not depend on previous experience but
      only on the consistency between stimulus and action effect in the present task.
      Taken altogether, the results suggest that children acquire response-effect
      associations automatically and that younger children are more likely to suffer
      from frequent goal neglect; i.e., they tend to forget the current action goal, so
      that their behavior is dominated by automatic, stimulus-triggered response
      tendencies.

PMID- 14962401
TI  - Task preparation and stimulus-evoked competition.
AB  - The authors investigated how task competition evoked by a stimulus that affords
      both a currently relevant and a temporarily irrelevant task is affected by
      invalid preparation, i.e., preparation for the irrelevant task. Although invalid
      preparation was associated with a general performance cost, effects of stimulus
      cued task competition were not enhanced on invalidly prepared trials. This result
      suggests that either preparation activates representations different from the
      ones by which stimulus cuing is mediated or that stimulus processing is postponed
      until invalid preparation has been corrected. In addition, invalid preparation
      resulted in impaired performance of the respective task when it became relevant
      on a subsequent trial. This result is consistent with the idea that competition
      due to invalid preparation is countered by task-specific inhibition.

PMID- 14962402
TI  - Frontal lobe dysfunction and everyday problem-solving: social and non-social
      contributions.
AB  - Everyday problem-solving involves both non-social executive processes, social and
      emotional processes, and draws upon social and practical knowledge. A series of
      studies including both adult-acquired lesions and neurodevelopmental disorders is
      reviewed examining problem-solving on a real-life-type task that involves
      generating a range of solutions to brief problem scenarios and selecting
      preferred solutions to solve the problems. Impairments in problem-solving are
      described in groups of participants with left anterior frontal lobe lesions,
      Tourette's syndrome and Asperger's syndrome. By contrast, healthy older people
      did not show problem-solving deficits on the same task. The possible
      contributions of non-social executive skills, social and emotional skills, and
      knowledge acquired from experience are each considered in relation to everyday
      performance. Multiple cognitive/emotional routes to the development of everyday
      life difficulties pose a complex challenge both in understanding the nature of
      the relevant processes and in developing adequate methods for management and
      rehabilitation.

PMID- 14962403
TI  - Using saccade tasks as a tool to analyze executive dysfunctions in schizophrenia.
AB  - Executive dysfunctions can be frequently observed in schizophrenia. They are more
      persistent than psychotic symptoms and are assumed to contribute to a variety of
      clinical signs of the disease. However, the cognitive mechanisms underlying
      dysexecutive behaviors are not yet understood. The aim of this article is to
      demonstrate how saccade tasks can be used to analyze the mechanisms involved in
      the dysexecutive syndrome of schizophrenic patients. There are numerous reports
      showing that schizophrenic patients make many unwanted reflexive saccades in the
      antisaccade task. These errors are usually explained by an impairment of a
      distinct inhibitory mechanism. However, unwanted reflexive saccades may also be
      secondary to a more fundamental deficit in activating goal-directed behavior.
      Recent theoretical and empirical approaches to this issue are reviewed and
      discussed. An integrative view of deficits in inhibition, goal-directed behavior,
      and working memory in schizophrenic patients is proposed.

PMID- 14962404
TI  - Cortico-subcortical contributions to executive control.
AB  - The term "executive functions" refers to a range of cognitive processes, their
      common feature being the coordination of information processing and action
      control. Cortico-subcortical circuits which connect the prefrontal cortex (PFC),
      the basal ganglia and the cerebellum via the thalamus are believed to serve as
      neuroanatomical substrates of executive processing. This paper focuses on
      information processing related to executive functions by the PFC and related
      subcortical regions. Findings are mainly derived from neuropsychological
      investigations of brain-damaged patients but also from imaging studies in healthy
      subjects. There is evidence for subtle differences between these regions with
      respect to the cognitive mechanisms contributing to inhibition of habitual
      responses, task management/multitasking and set shifting, although the data base
      is sparse so far.

PMID- 14962405
TI  - Wetting films of lipids in the development of sensitive interfaces. An
      electrochemical approach.
AB  - Solid-supported thin liquid films of lipids, contacting an electrolyte phase,
      turned out to be a dependable system in the field of bosensors. The
      investigations of these objects during the past decade reveal some of their
      intriguing features enabling the application in constructions of receptor part
      with 'two-dimensional' arrangement. As a model system, complementary to the other
      artificial analogs of biomembranes, the wetting films of lipids offer certain
      advantages concerning the compromise between the stability and flexibility of the
      molecular structures involved in sensing. The basic principles underlaying the
      techniques of formation, as well as the conditions of the films stability are
      emphasized in the present consized review. While no limitations are imposed by
      the way of preparation, the films seem especially profitable in conjunction with
      methods for electrochemical signal transduction. In this regard some prominent
      examples are discussed.

PMID- 14962406
TI  - Competitive adsorption of proteins and low-molecular-weight surfactants: computer
      simulation and microscopic imaging.
AB  - Proteins and low-molecular-weight (LMW) surfactants are used in the food industry
      as emulsifying (and foaming) ingredients and as stabilizers. These attributes are
      related to their ability to adsorb at fluid-fluid (and gas-fluid) interfaces
      lowering the interfacial (and surface) tension of liquids. Hence, the study of
      the properties of adsorbed layers of these molecules can be expected to lead to a
      better understanding of their effect on food products. Direct proof of the
      validity of mesoscopic models of systems of proteins and LMW surfactants can only
      be achieved by quantitative theoretical predictions being tested against both
      macroscopic and mesoscopic experiments. Computer simulation constitutes one of
      the few available tools to predict mathematically the behaviour of models of
      realistic complexity. Furthermore, experimental techniques such as atomic force
      microscopy (AFM) now allow high resolution imaging of these systems, providing
      the mesoscopic scale measurements to compare with the simulations. In this
      review, we bring together a number of related findings that have been generated
      at this mesoscopic level over the past few years. A useful simple model
      consisting of spherical particles interacting via bonded and unbonded forces is
      described, and the derived computer simulation results are compared against those
      from the imaging experiments. Special attention is paid to the adsorption of
      binary mixtures of proteins, mixtures of LMW surfactants, and also
      protein+surfactant mixed systems. We believe that further development of these
      mathematically well-defined physical models is necessary in order to achieve a
      proper understanding of the key physico-chemical processes involved.

PMID- 14962407
TI  - The primary electroviscous effect in colloidal suspensions.
AB  - Although a well-defined electrokinetic phenomenon, the primary electroviscous
      effect in dilute colloidal suspensions is still an unsolved problem. Most of the
      experimental tests of the different theories that we have studied have shown a
      lack of agreement. We have developed, during the last years, new theoretical
      approaches obtaining, finally, a much better agreement with the experimental
      results. The corrections are defined in two lines: first, it is accepted that
      ions present into the Stern layer, in which the fluid is stagnant, can
      tangentially move; second, it is accepted that the hydrodynamic interaction
      between colloidal particles exists although the suspensions are extremely
      diluted. The remarkable conclusion of our work is that the combination of both
      corrections should give correct theoretical results.

PMID- 14962408
TI  - Elementary swelling and gelling theories.
AB  - It has been experimentally illustrated that it is possible to form an n-phase
      thermodynamic system where n> or =2 and has a value which is limited by the
      properties of the system. For example, to attain limited chemical reversibility
      of a mineral matrix such as vermiculite using specific butyl ammonium
      vermiculite, it is necessary to reform chemical bonds using an additive and a
      particular ion. In other words, to obtain a similar thin film using exfoliated
      vermiculite as that obtained with natural vermiculite, hydrophobic or binding
      electrostatic bonds must be formed or reformed. It has also been observed that
      complementary structural compounds can be formed from other silicates, such as
      glycerine/sodium silicate. These compounds can also encase the vermiculite
      matrices. (Film Formation) is proportional to (A/Temp). (Pressure).(Ionic
      Content). Hence F=L(A/T)PE, where F=film formation, L=functional constant for the
      matrix compound, T=temperature, A=temperature constant, P=pressure,
      E=electrostatic force and P=force/area. Thus, F=LTE2 for unit area. SigmaF=pfL.
      TE2/SigmaPefl=F1, where P=the probability for film formation and SigmaPef(L) is
      the partition function for the film formation. This concept can be extended to a
      response geometric algorithm. This means that for every mineral matrix there is
      an algorithm to describe its formation or its response to an applied field. Thus
      deltasec2(E)tan(E1) is the response for (F1). V---, V1...Vn, F1...Fn1, ..., Fp,
      ...Fnp.

PMID- 14962409
TI  - The confocal scanning laser ophthalmoscopy ancillary study to the ocular
      hypertension treatment study: study design and baseline factors.
AB  - PURPOSE: To describe the study design of the Confocal Scanning Laser
      Ophthalmoscopy (CSLO) Ancillary Study to the Ocular Hypertension Treatment Study
      (OHTS) and to examine the associations between optic disk topography, and
      baseline demographic, clinical, and ocular factors at study entry. DESIGN: A
      randomized clinical trial. METHODS: Participants in this ancillary study were
      recruited from seven of the 22 OHTS clinical centers. Each participant completed
      imaging annually using a CSLO, the Heidelberg Retina Tomograph (HRT).
      Associations between HRT topographic optic disk measurements and intraocular
      pressure (IOP), baseline photographic estimates of horizontal and vertical cup-to
      disk diameter ratios by the OHTS Optic Disk Reading Center, baseline visual field
      indices, and demographic and clinical factors were assessed using linear mixed
      effects models. RESULTS: Four hundred thirty-nine participants had good quality
      images and were included in this baseline analysis. No associations between HRT
      topographic optic disk measurements and diabetes, systemic hypertension,
      cardiovascular disease, IOP, or visual function were found. The HRT topographic
      optic disk measurements were associated with baseline stereophotographic
      estimates of horizontal and vertical cup-to-disk diameter ratios. The strongest
      associations were found between stereophotographic assessment of horizontal and
      vertical cup-to-disk diameter ratios, and HRT cup-to-disk area ratio (r =.85
      and.84, respectively), rim-to-disk area ratio (r = -.85 and -.84, respectively),
      mean cup depth (r =.84 and.83, respectively), and cup area (r =.83 and.80,
      respectively). After adjusting for optic disk area, all HRT topographic optic
      disk measurements remained associated with stereophotographic assessment of
      horizontal and vertical cup-to-disk diameter ratios. CONCLUSIONS: The CSLO
      ancillary study to the OHTS is the first multicenter clinical trial to use CSLO
      imaging to monitor changes in the optic disk. At study entry, HRT topographic
      measurements corresponded well with both horizontal and vertical
      stereophotographic-based estimates of cup-to-disk diameter ratio in ocular
      hypertensive participants.

PMID- 14962410
TI  - Identifying early glaucoma with optical coherence tomography.
AB  - PURPOSE: To evaluate performance of optical coherence tomography (OCT) for
      detection of early glaucoma. DESIGN: Observational case-control study. METHODS: 
      SETTING: University-based tertiary care center. STUDY POPULATION: One eye from 50
      normals, 42 glaucoma suspects, and 59 early glaucoma patients meeting the
      following criteria: visual field (VF) mean deviation > or =-6.00 dB, age > or =40
      years, spherical refractive error < or =5 diopters, astigmatism < or =3 diopters,
      and visual acuity > or =20/30. OBSERVATION PROCEDURE: Early glaucoma by VF (EGVF)
      was described as repeatable abnormal achromatic VFs based on predefined criteria.
      Glaucoma suspects (GS) were defined as presence of glaucomatous disk appearance
      with normal achromatic VFs. OUTCOME MEASURES: Average nerve fiber layer thickness
      (NFLT) and NFLT in each of four quadrants and 12 clock-hour sectors. Receiver
      operating characteristic curves and sensitivity and specificity were used to
      assess the performance of OCT. RESULTS: Average NFLT was 128.4 +/- 15.4, 102.0 +/
      25.4, and 86.5 +/- 31.5 microm in normal, GS, and EGVF eyes, respectively.
      Normal eyes were different from both glaucoma groups (P <.001); NFLT in the
      superior quadrant and at the 11 o'clock position had the highest area under the
      receiver operating characteristic curve (.840 and.933) in the GS and EGVF groups
      (P =.03). The sensitivity of the OCT for detection of glaucoma was 71% and 85%
      for the GS and EGVF groups with specificity fixed at 90%. CONCLUSION: The OCT
      discriminates well between eyes with early perimetric glaucoma and normal eyes.
      However, its performance is less adequate in eyes with suspicious disk and normal
      VFs.

PMID- 14962411
TI  - Liver function tests in metastatic uveal melanoma.
AB  - PURPOSE: To evaluate trends in liver function tests before detection of liver
      metastases from uveal melanoma. DESIGN: Retrospective, comparative, observational
      case control study. METHODS:  SETTING: The Israel uveal melanoma center at the
      Hadassah University Hospital. PATIENT POPULATION: A total of 307 uveal melanoma
      patients who were diagnosed with uveal melanoma and followed between the years
      1988 and 1998. Of them, 30 metastatic patients who had regular follow-up by liver
      function tests (LFTs) and liver imaging were included in this study. Eighty
      nonmetastatic patients were randomly chosen as controls. OBSERVATION PROCEDURE:
      The medical records of the metastatic and control groups were reviewed
      documenting LFTs and liver imaging results. MAIN OUTCOME MEASURES: The mean level
      of each LFT, its sensitivity, specificity, and likelihood ratio at various time
      periods before the detection of metastases by liver imaging. RESULTS: At the time
      of diagnosis of liver metastases by imaging, 50% of patients had at least one
      abnormal LFT (compared with only 5% of the control group). While no change was
      noted in the mean serum levels of bilirubin, mean lactate dehydrogenase (LDH),
      alkaline-phosphatase, gamma glutamyl transpeptidase (gamma GTP) aspartate
      aminotrasferase, and alanine-aminotrasferase levels seem to rise, even within
      normal limits, during the 6 months before the detection of metastases. Based on
      likelihood ratios, alkaline-phosphatase and lactate dehydrogenase were the most
      predictive tests. Lactate dehydrogenase and aspartate-aminotransferase were
      already predictive at 80% of the upper normal limit, whereas alkaline-phosphatase
      and gamma-glutamyltransferase were most predictive at the upper normal limit.
      CONCLUSIONS: Monitoring the changes in selected LFTs, even within normal limits,
      can help predict metastatic uveal melanoma.

PMID- 14962412
TI  - Influence of intraoperative epithelial defects on outcomes in LASIK for myopia.
AB  - PURPOSE: To evaluate whether intraoperative epithelial defects have an adverse
      effect on achieving desired refractive outcomes following laser in situ
      keratomileusis (LASIK) for myopia. DESIGN: Observational retrospective case
      control study. METHODS: Thirty eyes that had intraoperative epithelial defects on
      the LASIK flap were compared with 60 randomly selected control eyes, matched for
      age, preoperative spherical equivalent, and preoperative cylinder, that had no
      intraoperative epithelial defects. Preoperative and postoperative clinical data
      were compared between the two groups. Statistical analyses were performed using
      analysis of means, analysis of variance, and the Student t test. Comparison
      variables included preoperative spherical equivalent, 3-month postoperative best
      corrected visual acuity, attempted correction, amount of undercorrection at 3
      months postoperatively, and whether LASIK enhancement was performed at 3 months
      postoperatively. RESULTS: Eyes with intraoperative epithelial defects showed more
      undercorrection at 3 months (P =.005), were more likely to have lost lines of
      visual acuity (P =.003), and underwent more enhancement procedures at 3 months (P
      =.004) compared with control eyes. CONCLUSIONS: Intraoperative epithelial defects
      during LASIK predispose eyes to increased wound healing, leading to myopic
      regression, irregular wound healing with loss of visual acuity, and increased
      need for enhancement procedures.

PMID- 14962413
TI  - The role of patient age and intraocular gas use in cataract progression after
      vitrectomy for macular holes and epiretinal membranes.
AB  - PURPOSE: To evaluate the rate of increase in nuclear sclerosis and posterior
      subcapsular cataracts in eyes as a function of patient age and use of
      intravitreal gas at the time of vitrectomy. DESIGN: Observational case series.
      METHODS: Nuclear sclerosis and posterior subcapsular cataracts were evaluated as
      a function of patient age and use of intravitreal gas at vitrectomy. SETTING: A
      clinical practice. STUDY POPULATION: The study population consisted of 301
      consecutive eyes. OBSERVATIONAL PROCEDURE: Nuclear sclerotic cataracts and
      posterior subcapsular cataracts were graded on a scale from 0 to 4.0 before and
      after vitrectomy. MAIN OUTCOME MEASURE: Linear regression analysis was performed
      to measure and compare the rate of change in cataract score over time based on
      patient age and use of intraocular gas. RESULTS: Nuclear sclerotic cataracts
      showed minimal increase in patients younger than 50 years of age after vitrectomy
      (0.13 grades/year). Nuclear sclerotic cataracts increased at a rate of 0.7 to 0.9
      grades/year (mean, 0.812) in patients aged 50 to 60 years, 60 to 70 years, 70 to
      80 years, and 80+ years, even though the baseline nuclear sclerosis scores were
      progressively greater for each decade. The increase in nuclear sclerotic
      cataracts in patients younger than 50 years of age was significantly less (P
      <.001) than in patients aged 50 years or older. Eyes with intraocular gas use had
      a higher rate of nuclear sclerosis progression (0.8 grades/year) compared with
      eyes without intraocular gas bubbles (0.5 grades/year; P <.001). Posterior
      subcapsular cataract scores showed minimal or no increases in all groups.
      CONCLUSIONS: Patients older than 50 years of age have a similar rate of increase
      in nuclear sclerotic cataracts, independent of age. The rate is approximately
      sixfold greater than in patients younger than 50 years of age. Intravitreal gas
      bubbles are associated with a nuclear sclerosis increase of approximately 60%
      compared with eyes without use of a gas bubble.

PMID- 14962414
TI  - Photodynamic therapy for age-related macular degeneration in a clinical setting:
      visual results and angiographic patterns.
AB  - PURPOSE: To evaluate the visual outcome of patients with subfoveal choroidal
      neovascularization due to age-related macular degeneration, who received
      photodynamic therapy (PTD) in a clinical setting and to identify potential
      predictive visual and angiographic factors. DESIGN: Interventional case series.
      METHODS: The study included 74 patients with subfoveal choroidal
      neovascularization who underwent PDT from January 2000 to March 2001 and
      completed at least 1 year follow-up. All patients received verteporfin PDT and
      were followed clinically, with fluorescein angiography (74 eyes), and with
      indocyanine green angiography (65 eyes). A review of the medical records and
      angiograms was performed. RESULTS: Mean follow-up was 15.6 months. Patients
      received a mean of 3.4 treatments per year. Sixty-six percent lost less than 3
      Snellen lines of visual acuity. Three patients (4%) experienced profound visual
      acuity loss to finger counting. Final visual acuity was positively correlated
      with lesion size and visual acuity at presentation. Visual outcome was worse in
      the presence of cystoid macular edema. On indocyanine green angiography, a round
      hypofluorescent spot was seen at the site of the PDT, with maintenance of medium
      and large choroidal vessels. CONCLUSION: Smaller lesion size and better visual
      acuity at presentation were good predictive signs, whereas cystoid macular edema
      was found to be a poor prognostic sign for visual outcome following PDT.

PMID- 14962415
TI  - The determinants of participation in activities of daily living in people with
      impaired vision.
AB  - PURPOSE: To investigate the determinants of participation in daily activities in
      people with impaired vision using the Impact of Vision Impairment (IVI)
      instrument. DESIGN: Cross-sectional study. METHODS: We recruited 319 participants
      with no vision rehabilitation history, distance visual acuity (VA) <6/12 (better
      eye), the ability to converse in English, and 18 years or older. Participants
      completed the 32-item IVI questionnaire and provided demographic, personal,
      cultural, and environmental details on vision-related functioning. Visual acuity
      data were either abstracted from the participants' files or assessed by qualified
      personnel. Participants also completed the SF-12 to evaluate physical (PCS-12)
      and mental health (MCS-12). RESULTS: The areas of greatest restriction of
      participation were associated with reading, outdoor mobility, participation in
      leisure activities, and shopping. In stepwise linear regression presenting VA,
      the PCS-12 and MCS-12 explained the variance in leisure and work (60 participants
      or 19%), consumer and social interaction (92 participants or 30%), household and
      personal care (76 participants or 24%), mobility (92 participants or 30%),
      emotional reaction to visual loss and (106 participants or 33%), and total IVI
      score (114 participants or 36%). Having age-related macular degeneration
      contributed marginally to the IVI domains and total score (P <.05-.01), except
      for the emotional domain. Belonging to a social group explained 3% and 2% of the
      variance in the consumer and social interaction and emotional domains,
      respectively (P <.05). CONCLUSIONS: Distance VA and physical and mental health
      explained more than a third of the variance of the total score, suggesting that
      an intervention aimed at improving quality of life may include strategies to
      improve not only vision-related rehabilitation but also mental and physical
      health.

PMID- 14962416
TI  - Ophthalmologic findings in a large pedigree of 11778/Haplogroup J Leber
      hereditary optic neuropathy.
AB  - PURPOSE: To report the ophthalmologic characteristics of a newly identified seven
      generation pedigree of 11778/Haplogroup J Leber hereditary optic neuropathy
      consisting of 328 living individuals, 111 of whom are maternally related. DESIGN:
      Observational population cohort study. METHODS: This prospective study of a large
      Brazilian Leber hereditary optic neuropathy pedigree was carried out as a field
      investigation in Brazil. We describe the ophthalmologic findings of 192 eyes from
      96 maternally related individuals of this pedigree. Spouses were used as control
      subjects. We conducted comprehensive neuro-ophthalmologic examinations with
      psychophysical tests, Humphrey visual fields, and fundus photographs. We also
      correlated the ophthalmologic findings with the previously published
      epidemiologic assessment of risk factors. RESULTS: We examined 76 carriers and 20
      affected individuals. The affected individuals showed severe disease with a mean
      visual acuity of 2.04 logarithm of the minimal angle of resolution and without
      evidence of recovery. All the affected individuals showed diffuse optic atrophy
      with a cup-to-disk ratio greater than 0.5 in 55% of cases. Moreover, among
      Affected individuals, smokers had a poorer visual acuity (P =.002). Among
      carriers there were several subclinical abnormalities, including microangiopathy,
      swelling of nerve fibers, and visual field abnormalities that did not correlate
      with tobacco or alcohol consumption. CONCLUSIONS: Our results demonstrate a
      significant influence of environmental risk factors, particularly smoking, for
      developing Leber hereditary optic neuropathy and for the severity of its clinical
      expression. However, smoking did not correlate with the subclinical abnormalities
      detected in carriers. Moreover, subclinical abnormalities were equally
      distributed between gender.

PMID- 14962417
TI  - Comparison of the amblyopia treatment study HOTV and electronic-early treatment
      of diabetic retinopathy study visual acuity protocols in children aged 5 to 12
      years.
AB  - PURPOSE: To compare two established visual acuity protocols: the Amblyopia
      Treatment Study HOTV (ATS HOTV) visual acuity protocol and the Electronic-Early
      Treatment of Diabetic Retinopathy Study (E-ETDRS) protocol, in children aged 5 to
      12 years. DESIGN: Prospective cohort study. METHODS: Crowded HOTV optotypes and
      crowded ETDRS optotypes were presented to 236 consecutive children aged 5 to 12
      years using an electronic visual acuity tester (Palm handheld, personal computer,
      and monitor). Twenty-three percent of the children were classified as amblyopic,
      35% as having uncorrected refractive error, 36% as normal, and 6% as other.
      Visual acuity test results were converted to logarithm of minimal angle of
      resolution (logMAR) units for analysis. RESULTS: In developmentally normal
      children (n = 230), testability was 100% for HOTV in 5- to 12-year-olds and 100%
      for E-ETDRS in 7- to 12-year-olds. The E-ETDRS testing could be completed in 52%
      of 5-year-olds and in 87% of 6-year-olds. Visual acuity performance was better
      when measured by HOTV compared with E-ETDRS (median difference 0.06 logMAR [three
      letters on a chart with five letters/line], P =.0001), and the difference was
      found in normal eyes, eyes with refractive error, and amblyopic eyes.
      CONCLUSIONS: The ATS HOTV protocol yields slightly better visual acuity
      performance compared with E-ETDRS in 5- to 12-year-olds, but on average by less
      than a logMAR level. This systematic difference is important when a physician
      changes testing modality as a child matures and should be considered when
      interpreting the results of recent and ongoing clinical trials in amblyopia.

PMID- 14962418
TI  - Orientational contrast sensitivity and chromatic contrast thresholds in multiple
      sclerosis.
AB  - PURPOSE: To investigate abnormalities of orientational contrast sensitivity (CS)
      and chromatic contrast threshold (CCT) in multiple sclerosis (MS). DESIGN: Case
      control study. METHODS: Nine subjects (mean age, 42 +/- 11 years; range, 20-62
      years) with MS, an expanded disability status scale of 3 or less, and normal
      visual acuity (VA) (logarithm of the minimum angle of resolution [logMAR] VA less
      than.1) in the tested eye were age-matched with 20 controls. Achromatic CS and
      CCT were measured using static, computer-generated sinusoidal gratings displayed
      on a high-resolution monitor. The CS and CCT of each subject were determined
      using a randomized double-staircase reversal algorithm; CS was measured at five
      spatial frequencies with horizontal orientation and three with vertical
      orientation; CCT was measured along the red-green and tritan confusion axes. The
      sensitivity thresholds of subjects were examined in relation to the mean
      sensitivity of controls for each spatial frequency. RESULTS: Two subjects had
      loss of horizontal and vertical CS, and three had isolated vertical loss. When
      compared with the control mean, there were significant reductions in red-green (P
      =.016) and tritan (P =.016) discrimination thresholds. CONCLUSION: This study
      used a computerized psychophysical test designed to minimize many of the test
      errors associated with earlier studies. It provides confirmatory evidence that MS
      may be associated with a loss of orientational CS and color vision, in the
      absence of reduced VA.

PMID- 14962419
TI  - Perfluorocarbon perfused vitrectomy: animal studies.
AB  - PURPOSE: To investigate the feasibility and advantages of using perfluorocarbon
      liquid (PCL) perfusion to remove vitreous during suction-cutting vitrectomy in
      rabbit and pig eyes. DESIGN: Experimental study. METHODS: Balanced salt solution
      (BSS) was replaced by PCL perfusion during experimental vitrectomy. Oxygenated or
      nonoxygenated PCL was used in a recycling or a nonrecycling system. Recycling was
      achieved by two systems: a manual recycling system or a closed-loop system. The
      experiments in this study consisted of: an in vitro solubility observation,
      safety and feasibility of vitrectomy in rabbit eyes, effectiveness of vitrectomy
      with equal vitrectomy time in rabbit eyes, and retinal stability and pigment and
      blood dispersion in porcine eyes. Toxicity was assessed by a complete ophthalmic
      examination, endothelial cell count, electroretinography, and histopathology.
      RESULTS: Vitreous, blood, and pigments were immiscible in PCL. Manual recycling
      required less amounts of PCL than nonrecycling (15 vs 25 cc). Oxygenated and
      nonoxygenated PCL were not toxic. Perfluorocarbon liquid infusion removed more
      vitreous than balanced salt solution in a 3-minute vitrectomy time using the same
      settings on the vitrectomy machine. The PCL infusion in porcine eyes stabilized
      the retina and isolated vitreous cavity from pigment and blood and maintained a
      clear vitreous cavity. CONCLUSIONS: These data indicate that perfusion of PCL can
      be used to remove vitreous with a suction-cutting probe in rabbit and pig eyes.
      Retinal stability and isolation of the vitreous cavity at the time of vitreous
      removal along with PCL immiscibility and its specific gravity suggest that PCL
      has a potential clinical use as an irrigating solution to remove vitreous.

PMID- 14962420
TI  - Surgical outcomes of combined phacoemulsification and glaucoma drainage implant
      surgery for Asian patients with refractory glaucoma with cataract.
AB  - PURPOSE: To examine the safety and efficacy of combined phacoemulsification and
      glaucoma drainage implant surgery in providing reduction of intraocular pressure
      (IOP) and visual rehabilitation in eyes with refractory glaucoma and cataract.
      DESIGN: Interventional case series. METHODS: A retrospective chart review was
      performed on all subjects who underwent combined phacoemulsification with
      intraocular lens implantation and glaucoma drainage implant surgery by a single
      surgeon at the National University Hospital, Singapore. The implants used were
      the 185 mm2 Ahmed glaucoma valve and the 350 mm2 Baerveldt glaucoma implant. In
      terms of IOP, a complete success was defined as IOP of between 6 to 21 mm Hg
      without medication, qualified success as IOP between 6 to 21 mm Hg with one or
      more medication, and failure as a sustained IOP of >21 mm Hg or <6 mm Hg with or
      without one or more medication on two or more visits. RESULTS: A total of 32
      combined phacoemulsification and glaucoma implant surgeries in 32 patients was
      performed. All patients were of Asian origin, and the mean age was 58 +/- 16
      years (range, 20-78 years). The Baerveldt glaucoma implant and Ahmed glaucoma
      valve implant were inserted in 16 eyes each. With a mean follow-up of 13 +/- 5
      months (range 6 to 22 months), IOP was reduced from a mean of 28.0 +/- 11.5 mm Hg
      to 15.2 +/- 6.0 mm Hg postoperatively (P <.0001), whereas the number of
      antiglaucoma medications decreased from a mean of 2.4 +/- 1.4 to.3 +/-.7 (P
      <.0001) at last follow-up. Overall, there were 24 eyes (75%) that were classified
      as complete successes, 4 eyes (12.5%) that were qualified successes, and 4 eyes
      that failed (12.5%). Twenty-three eyes (72%) had improvement of visual acuity,
      while only one eye had a loss of more than 1 line of Snellen acuity. There was no
      case that encountered an intraoperative complication, and postoperative
      complications occurred in 12 eyes (38%), the most common of which was hypotony
      (in six eyes, 19%). CONCLUSION: For subjects with refractory glaucoma and
      cataract, combined phacoemulsification and glaucoma drainage implant surgery
      provide good visual rehabilitation and control of IOP, with low incidence of
      complications.

PMID- 14962421
TI  - Impact of phototherapeutic keratectomy on the outcome of subsequent penetrating
      keratoplasty in patients with stromal corneal dystrophies.
AB  - PURPOSE: To examine the impact of previous phototherapeutic keratectomy (PTK) on
      the outcome of subsequent penetrating keratoplasty (PK) in patients with stromal
      corneal dystrophies. DESIGN: Retrospective, cross-sectional, clinical single
      center study. METHODS:  PATIENT POPULATION: Fifteen patients (21 eyes) age 39.9
      +/- 11.4 years. INCLUSION CRITERIA: Primary homologous PK performed in phakic
      patients with granular or macular dystrophy; no use of combined surgical
      procedures; defined graft size and technique. The study group comprised eight
      eyes of five patients, PK performed 3.7 +/- 2.3 years after PTK. The control
      group (no previous PTK) comprised 13 eyes of 10 patients. In both groups, 38% had
      granular and 62% had macular dystrophy. Intervention Procedures: Phototherapeutic
      keratectomy was performed using a 193 nm excimer laser. All PKs were also
      performed using this laser, with trephination using a metal mask. Subjective
      refractometry (trial lenses), standard keratometry (Zeiss ophthalmometer), and
      corneal topography (Tomey TMS-1) were performed preoperatively, 6 months after
      PK, and after first and second suture removal (1.1 +/- 0.2 years; 1.6 +/- 0.2
      years). MAIN OUTCOME MEASURES: Keratometric, topographic net astigmatism, and
      refractive cylinder; keratometric and topographic central power; best-corrected
      visual acuity (BCVA); surface regularity index (SRI), surface asymmetry index
      (SAI), potential visual acuity (PVA). RESULTS: Refractive power and astigmatism,
      BCVA, and PVA values did not differ significantly between the two groups at any
      time-point; SRI tended to be better in the study group after first suture removal
      (P =.05). CONCLUSION: Preceding PTK does not appear to impair the outcome of
      subsequent penetrating keratoplasty in stromal corneal dystrophy patients.

PMID- 14962422
TI  - An in vivo study comparing the ocular absorption of levofloxacin and
      ciprofloxacin prior to phacoemulsification.
AB  - PURPOSE: To compare aqueous humor concentrations of levofloxacin vs ciprofloxacin
      when used as prophylactic medications before phacoemulsification. DESIGN:
      Patients (n = 93) were randomly assigned to receive either 0.5% levofloxacin
      (Quixin) or 0.3% ciprofloxacin (Ciloxan) using one of the following dosing
      regimens: (A) 1 to 2 drops four times a day for 2 days preoperatively; (B) 5
      doses (1 to 2 drops) delivered every 10 minutes in the hour immediately preceding
      surgery; or (C) the combination of A and B. METHODS: Aqueous samples (0.1 ml)
      were obtained immediately before surgery, and drug concentrations were measured
      using high performance liquid chromatography/mass spectrometry. RESULTS: The mean
      concentration of levofloxacin in the aqueous humor was significantly greater than
      that of ciprofloxacin in all treatment groups (P <.001): 284.8 vs 67.4 microg/ml
      (regimen A); 1,135.6 vs 185.6 microg/ml (regimen B); and 1,618.6 vs 241.5
      (regimen C). Dosing regimen B delivered significantly more drug to the aqueous
      humor than regimen A for both levofloxacin (P < or =.001) and ciprofloxacin (P
      =.004). Dosing regimen C delivered significantly more drug to the aqueous humor
      than regimen B for levofloxacin (P =.05) but not for ciprofloxacin (P =.384).
      CONCLUSIONS: Although the concentration of active drug in levofloxacin is
      approximately 1.7-fold higher than that in ciprofloxacin, the aqueous
      concentration of levofloxacin after topical administration was four to seven
      times greater than ciprofloxacin; these differences were statistically
      significant. With dosing regimens B and C, levofloxacin concentrations in the
      aqueous humor were above the MIC90 for most common ocular pathogens, including
      Staphylococcus and Streptococcus species. Ciprofloxacin did not reach such
      concentrations in any treatment group.

PMID- 14962423
TI  - The correlation between fluorescein angiographic and optical coherence
      tomographic features in clinically significant diabetic macular edema.
AB  - PURPOSE: To assess the correlation between the features of optical coherence
      tomography (OCT) and fluorescein angiography in clinically significant diabetic
      macular edema. DESIGN: Retrospective observational case series. METHODS: This
      study involved 145 eyes (91 patients) with clinically significant diabetic
      macular edema. The fluorescein angiography features were categorized into focal
      leakage type, diffuse leakage type, and diffuse cystoid leakage type. The OCT
      features were categorized into four types: type 1, thickening with homogeneous
      optical reflectivity; type 2, thickening with markedly decreased optical
      reflectivity in the outer retinal layer; type 3A, foveolar detachment without
      traction; and type 3B, foveolar detachment with apparent vitreofoveal traction.
      The correlation between fluorescein angiography types and OCT types were
      analyzed, and their associations with visual acuity, central foveal thickness.
      and stages of diabetic retinopathy were evaluated. RESULTS: The prevalence of OCT
      type 1 was higher in the focal leakage type (73.0%) and in the diffuse leakage
      type (58.9%) than in the diffuse cystoid leakage type (3.8%) of fluorescein
      angiography (P <.0001). The prevalence of OCT type 2 and 3A was higher in the
      diffuse cystoid leakage type (57.7% and 34.6%, respectively) than in the focal
      leakage type (20.6% and 3.2%) or diffuse leakage type(28.6% and 10.7%; P <.0001).
      The stages of retinopathy correlated with fluorescein angiography types (P
      =.016). Optical coherence tomography type 1 and the focal leakage type of
      fluorescein angiography showed the least foveal thickness and the best visual
      acuity (P <.05). CONCLUSIONS: There was a significant correlation between the
      features of OCT and fluorescein angiography in clinically significant diabetic
      macular edema. The combined data from both OCT and fluorescein angiography may
      provide a clearer understanding of the anatomic and physiologic characteristics
      of clinically significant diabetic macular edema.

PMID- 14962424
TI  - Impression cytology in the diagnosis of acanthamoeba keratitis with surface
      involvement.
AB  - PURPOSE: To evaluate the use of impression cytology in the diagnosis of
      Acanthamoeba keratitis with surface involvement. DESIGN: Observational case
      series. METHODS: Three patients with culture-proven superficial Acanthamoeba
      keratitis were studied. Patients' medical records were reviewed for clinical
      information, treatment procedures and disease course. Impression cytology
      specimens taken from the cornea of those patients were processed and observed by
      bright field microscopy. The main outcome measure was the cytopathological
      examination and identification of amoebic organisms. RESULTS: In each of these
      three patients, impression cytology specimens revealed the amoeba cysts. Some
      specimens also showed pleomorphic trophozoites with typical amoeba nuclei.
      CONCLUSION: Corneal impression cytology successfully detected the cysts and
      trophozoites of Acanthamoeba from patients with superficial amoeba keratitis.
      This indicates that impression cytology can be a useful technique to facilitate
      early diagnosis of Acanthamoeba keratitis with surface involvement.

PMID- 14962425
TI  - Clinical characteristics of microbial keratitis in a university hospital in
      Taiwan.
AB  - PURPOSE: To analyze the clinical and microbiological characteristics of microbial
      keratitis at the National Taiwan University Hospital in the preceding 10 years.
      DESIGN: Retrospective cross-sectional study. METHODS: Medical records were
      reviewed for all patients with clinically diagnosed microbial keratitis
      presenting at the National Taiwan University Hospital from January 1992 to
      December 2001. Risk factors, microbial isolations, clinical patterns, treatment,
      and outcomes were analyzed. RESULTS: Microbial keratitis was diagnosed for 476
      eyes in 453 patients (220 female and 233 male; mean age, 40.7 years). Pseudomonas
      species were the most commonly isolated organisms (37.7%), followed by fungi
      (13.5%), staphylococci (8.4%), nontuberculous mycobacteria (7.9%), streptococci
      (7.6%), and Acanthamoeba (4.4%). Contact-lens wear was the most common
      predisposing factor (44.3%). Medical treatment was successful for a total of 344
      eyes (72.3%), with 132 eyes (27.7%) requiring surgery. The duration from symptom
      onset to diagnosis of microbial keratitis was statistically significantly shorter
      for the cases treated medically than the cases treated surgically (7.70 +/- 14.37
      and 20.53 +/- 28.85 days, respectively, p =.000000332). Response to medical
      treatment was more favorable for bacterial infection (except nontuberculous
      mycobacterial infection) as compared with fungal or Acanthamoeba infection. A
      total of 84.4% of pseudomonal keratitis cases were cured by medical treatment,
      while 85% of nontuberculous mycobacterial keratitis cases eventually required
      surgical treatment to control the infection. CONCLUSION: Contact-lens related
      pseudomonal keratitis was the most common form of microbial keratitis in Taiwan.
      Early diagnosis and prompt treatment are important for successful management of
      microbial keratitis.

PMID- 14962426
TI  - Antiinflammatory therapy for dry eye.
AB  - PURPOSE: To present evidence establishing the relationship between inflammation
      and dry eye and supporting the use of antiinflammatory therapy for dry eye.
      DESIGN: Analysis of literature. METHODS: Research studies that evaluated
      inflammation in dry eye pathogenesis and clinical trials of antiinflammatory
      therapies for dry eye were reviewed. RESULTS: There is increasing evidence that
      decreased tear secretion, decreased tear turnover, and desiccation promote
      inflammation on the ocular surface. An increase in soluble mediators (cytokines
      and proteases) in the tear fluid, adhesion molecule expression by the
      conjunctival epithelium, and T-cell infiltration of the conjunctiva have been
      observed in dry eye patients. This inflammation appears to have a role in the
      pathogenesis of the ocular surface epithelial disease, termed
      keratoconjunctivitis sicca (KCS), that develops in dry eye. Clinical improvement
      of KCS has been observed after therapy with antiinflammatory agents including
      corticosteroids, cyclosporin and doxycycline. Cyclosporin A emulsion was approved
      by the Food and Drug Administration as therapy for dry eye. Randomized placebo
      controlled FDA clinical trials showed that cyclosporine A was superior to vehicle
      in stimulating aqueous tear production, decreasing corneal punctuate fluorescein
      staining, reducing symptoms of blurred vision, and decreasing artificial tear use
      in patients with KCS. No ocular or systemic toxicity was observed from this
      medication. CONCLUSIONS: Ocular surface and lacrimal gland inflammation has been
      identified in dry eye that plays a role in the pathogenesis of KCS.
      Antiinflammatory therapy has efficacy for treating KCS. Cyclosporin A is the
      first FDA approved therapy for this indication. It improved signs and symptoms of
      KCS, and it is safe for long-term use.

PMID- 14962427
TI  - Endophthalmitis after penetrating keratoplasty: microbiologic spectrum and
      susceptibility of isolates.
AB  - PURPOSE: To present the microbial spectrum and susceptibilities of isolates in
      endophthalmitis following penetrating keratoplasty. DESIGN: Interventional case
      series. METHODS: The 1,074 consecutive cases of endophthalmitis presenting to
      Wills Eye Hospital between 1989 and 2000 were reviewed. Fourteen patients with
      endophthalmitis after penetrating keratoplasty were identified, and vitreous
      biopsy isolates from these patients were examined. RESULTS: Eleven (78.6%) of 14
      vitreous samples were culture-positive, and two others (14.3%) had organisms
      viewed on pathology specimen, for a total of 13 (92.9%) organism-proven cases of
      endophthalmitis. Isolates included 10 (76.9%) gram-positive cocci (six
      Streptococcus sp., three Staphylococcus sp., one identified on pathology specimen
      only) and three (23.1%) gram-negative organisms (Proteus mirabilis, Serratia
      marcescens, one identified on pathology specimen only). Susceptibilities to
      organism-appropriate antibiotic testing are reported, including cefazolin (six of
      eight, 75.0%), ciprofloxacin (four of seven, 57.1%), nafcillin (four of six,
      66.7%), and vancomycin (seven of seven, 100.0%). CONCLUSION: This is the largest
      series on microbial susceptibilities in postpenetrating keratoplasty
      endophthalmitis. We report a high percentage of culture-positivity, and a high
      incidence of gram-positive species, and in particular Streptococcus species, with
      all tested gram-positive organisms susceptible to vancomycin.

PMID- 14962428
TI  - Histology of the vitreoretinal interface after staining of the internal limiting
      membrane using glucose 5% diluted indocyanine and infracyanine green.
AB  - PURPOSE: To evaluate the effect of indocyanine green (ICG) diluted with glucose
      5% on the human retina in an experimental setting in postmortem eyes and during
      surgery for macular hole formation. DESIGN: Histopathological evaluation.
      METHODS: Possible adverse effects of two different solutions of 0.05% ICG
      (Pulsion, Munich, Germany; and Infracyanine, Laboratoire SERB, Paris, France)
      diluted with glucose 5% were evaluated in four eyes of two donors. In one eye of
      each donor, the ICG-stained macula was illuminated with 380 to 760 nm using the
      light source of a commonly used vitrectomy machine. In the other eye, ICG was
      applied to the macula without illumination. The retinal specimens were evaluated
      using light- and electron microscopy. Additionally, the ultrastructure of the
      internal limiting membrane (ILM) of four eyes that underwent ICG-assisted
      vitrectomy for macular hole formation was examined. RESULTS: In the postmortem
      study, both solutions of ICG caused significant morphologic alterations of the
      inner retina after light exposure. There was disorganization of the inner retina
      and complete loss of ILM after application of the dye and illumination. In
      contrast, no abnormalities were found after application of the dye without
      illumination and in unstained control specimens. No differences were noted
      between the two ICG products. Specimens of the ILM harvested during vitrectomy
      revealed cellular elements adjacent to the retinal side of the ILM. CONCLUSIONS:
      Staining of the ILM using ICG diluted in glucose 5% followed by illumination
      might induce an adverse effect on the inner retina and may result in an
      alteration of the cleavage plane from the ILM to the innermost retinal layers.

PMID- 14962429
TI  - Markedly increased central corneal thickness: an unrecognized finding in
      congenital aniridia.
AB  - PURPOSE: To describe central corneal thickness among patients diagnosed with
      congenital aniridia. DESIGN: Prospective noninterventional case series. METHODS:
      We identified patients carrying the clinical diagnosis of congenital aniridia and
      performed complete ophthalmic examinations. Eyes with known corneal pathology
      were excluded. Central corneal thickness was determined as the mean of five
      measurements per eye, acquired by matching ultrasonic pachymeters at two clinical
      sites. RESULTS: Seventeen patients were identified at two sites; 32 eyes
      qualified for inclusion. The average central corneal thickness of the qualifying
      eyes was 631.6 +/- 50.8 microM. CONCLUSION: Markedly increased central corneal
      thickness appears to be a previously unrecognized aspect of congenital aniridia.
      This may lead to incorrect estimates of intraocular pressure by applanation
      techniques and highlights the importance of monitoring patients with aniridia for
      the development of glaucoma through regular gonioscopy and optic nerve
      examination.

PMID- 14962430
TI  - Can patients guess their intraocular pressure?
AB  - PURPOSE: To determine whether patients can guess their intraocular pressure
      (IOP). DESIGN: Patient survey. METHODS: We asked consecutive patients to guess
      their IOP and then indicate the IOP and the symptoms that allowed them to guess.
      RESULTS: Of 132 patients, 22 (17%) believed they could guess their IOP, usually
      based on a periocular symptom (n = 20, 91%). Nine of these patients (45%)
      correctly identified whether they were below or above the pressure indicated by
      the symptom. In two patients who required no symptoms to guess and in nine whose
      IOP was above their symptom threshold, the mean difference of the guessed IOP
      from the actual IOP did not differ (+/- 3.3 mm Hg) from that of control patients
      (+/- 2.1 mm Hg, n = 50; r =.19). CONCLUSIONS: Patients who believe they can guess
      their IOP appear as often inaccurate as accurate in assessing their IOP related
      to a symptom threshold and as accurate as patients who claim they cannot guess
      their IOP.

PMID- 14962431
TI  - Optical coherence tomography of chronic solar retinopathy.
AB  - PURPOSE: To describe the optical coherence tomographic findings in eight eyes of
      four patients with chronic solar retinopathy. All patients had a history of sun
      gazing months to years prior to presentation. DESIGN: Retrospective case series.
      METHODS: Patients were examined using biomicroscopy performed by two or more
      experienced vitreoretinal specialists. All eight eyes had optical coherence
      tomography performed at the time of initial examination. RESULTS: All patients
      had a history of sun gazing and decreased vision in both eyes. On biomicroscopy,
      all eyes had a small, irregularly-shaped lamellar defect in the foveal center. No
      posterior vitreous detachment was present in any eye. Optical coherence
      tomography revealed a hyporeflective space at the level of the outer neurosensory
      retina and retinal pigment epithelium in all eyes. CONCLUSION: Optical coherence
      tomography demonstrates a characteristic hyporeflective space in the outer retina
      in patients with chronic solar retinopathy. These findings correlate with the
      histopathology of this condition and may be a useful clinical tool in confirming
      its diagnosis.

PMID- 14962432
TI  - Use of the RetCam 120 for fundus evaluation in uncooperative children.
AB  - PURPOSE: To report our experience using the RetCam 120 to evaluate suspected
      retinal pathology in children who did not cooperate for standard in-office
      examination. DESIGN: Interventional case series. METHODS: We reviewed charts of
      eight consecutive uncooperative children with suspected fundus abnormalities that
      were photographed using the RetCam 120 as a routine part of patient care.
      RESULTS: Three uncooperative children with suspected pathology required RetCam
      120 photos because of inadequate fundus examination. Five had pathology or
      suspected pathology that required more detailed examination. In all of these
      children, we were able to reach or rule out a diagnosis. CONCLUSION: The Retcam
      120 digital fundus camera has utility as an in-office diagnostic tool for fundus
      examination of poorly cooperative children and may be a good alternative to
      examination under anesthesia or sedation in selected cases.

PMID- 14962433
TI  - Oculogyric crisis in patients taking cetirizine.
AB  - PURPOSE: To report oculogyric crisis in patients receiving cetirizine and inform
      clinicians on the characteristics of this drug-induced ocular side effect.
      METHODS: For this retrospective, observational case series, case reports were
      collected from the National Registry of Drug-Induced Ocular Side Effects (Casey
      Eye Institute, Portland, Oregon). The World Health Organization Causality
      Assessment Guide of Suspected Adverse Reactions was used to categorize the cases.
      RESULTS: Nine cases were reported, with eight occurring in the pediatric age
      group. Dosage ranged from 5 to 10 mg orally and onset of symptoms ranged from 3
      to 184 days. Six cases of oculogyric crisis had positive rechallenge data. Eight
      cases had complete neurologic consultation including radiographic studies.
      CONCLUSIONS: Cetirizine can cause oculogyric crisis, especially in the pediatric
      age group. Extensive neurologic workups may be avoided if clinicians recognize
      this drug-induced ocular side effect.

PMID- 14962434
TI  - Four cases of normal-tension glaucoma with disk hemorrhage combined with branch
      retinal vein occlusion in the contralateral eye.
AB  - PURPOSE: To report four cases of normal-tension glaucoma with disk hemorrhage in
      one eye and branch retinal vein occlusion in the contralateral eye. DESIGN:
      Observational case series. METHODS: Four cases of normal-tension glaucoma with
      disk hemorrhage in one eye and branch retinal vein occlusion in the contralateral
      eye were detected within a 1-year period. RESULTS: Mean patient age was 57 +/- 10
      years. Three patients had systemic hypertension, two bilateral normal-tension
      glaucoma, and all four bilateral peripapillary atrophy. There was no significant
      difference in intraocular pressure between the disk hemorrhage eyes and the
      contralateral eyes with branch retinal vein occlusion. CONCLUSION: Some normal
      tension glaucoma patients with disk hemorrhage may have a pathogenic mechanism in
      combination with branch retinal vein occlusion.

PMID- 14962435
TI  - Autoclavable wide-angle contact lens for vitreous surgery.
AB  - PURPOSE: To evaluate an autoclavable self-stabilizing wide-angle contact lens for
      vitrectomy. DESIGN: Observational study. METHOD: The wide-angle contact lens has
      two lens pieces within a high temperature-resistant (150 C) plastic casing. The
      inferior lens with footplates is made of acrylic and the superior of glass.
      During surgery the lens is used as the self-stabilizing wide-angle contact lens
      with improved stability on the eye. RESULT: The lens enables the surgeon to
      address the peripheral retina with less dependence on the assistant. The lens is
      sterilizable by autoclaving. The field of view of the wide-angle lens is 106
      degrees static and 127 degrees dynamic view. CONCLUSION: The autoclavable self
      stabilizing wide-angle lens reduces the cost and time for sterilization.

PMID- 14962436
TI  - Wavefront analysis of an eye with monocular triplopia and nuclear cataract.
AB  - PURPOSE: To determine whether higher-order aberrations explain patient-reported
      monocular triplopia. DESIGN: Observational case report. METHOD: A patient
      complaining of monocular triplopia was examined with a Hartmann-Shack aberrometer
      to determine whether higher-order wavefront aberrations could account for the
      triplopia. The patient had a mild nuclear cataract; measurements were made before
      and after lensectomy. The retinal image was simulated using the Zernike
      polynomials. RESULT: Spherical aberration (-0.18 microm, 4 mm pupil) and trefoil
      aberration (-0.16 microm) were increased. The simulated retinal image had a
      triple configuration similar to the subjective image reported by the patient.
      After cataract surgery, the subjective triplopia disappeared; spherical, and
      trefoil aberrations were markedly decreased. CONCLUSION: The monocular triplopia
      probably stemmed from combined effects of spherical and trefoil aberrations
      caused by the nuclear cataract.

PMID- 14962437
TI  - Corneal arcus and hyperlipidemia: findings from an older population.
AB  - PURPOSE: To quantify the association between arcus and hyperlipidemia in an older
      population. DESIGN: Cross-sectional population-based study. METHODS: Arcus and
      serum lipids were measured in the Blue Mountains Eye Study (n = 3,654, aged >49
      years). Arcus was graded as absent, partial (<180 degrees) or circumferential (>
      or =180 degrees). Associations between arcus and hyperlipidemia were assessed
      using logistic regression, adjusting for age and vascular risk factors. RESULTS:
      Arcus was strongly associated with age (P <.0001). After age adjustment, arcus
      was associated with male sex (P <.01) and diabetes (P <.02) but not with
      hypertension or smoking. Corneal arcus was significantly associated with
      progressively higher levels of total cholesterol over 5 mmol/l. Adjusted odds
      increased from 1.6 for cholesterol 6.0 to 6.9 mmol/l to 4.6 for cholesterol >8.0
      mmol/l, and was 1.9 for high triglyceride >3.0 mmol/l. CONCLUSION: This
      population-based finding confirms that corneal arcus was associated with
      hypercholesterolemia and hypertriglyceridemia in older persons.

PMID- 14962438
TI  - Noninvasive neuroimaging of basilar artery dolichoectasia in a patient with an
      isolated abducens nerve paresis.
AB  - PURPOSE: To describe the neuroimaging findings in a patient with an isolated
      abducens nerve palsy caused by a dolichoectatic basilar artery. DESIGN:
      Retrospective case report. METHODS: A 65-year-old man presented with a 3-year
      history of gradually worsening horizontal double vision. He subsequently
      underwent magnetic resonance imaging, magnetic resonance angiography, and
      computed tomographic angiography. RESULTS: Neuroimaging revealed dolichoectasia
      of the basilar artery. The enlarged, tortuous vessel appeared to be compressing
      the subarachnoid portion of the nerve at its exit from the brainstem. CONCLUSION:
      Noninvasive neuroimaging studies are sufficient to establish a diagnosis of
      basilar artery dolichoectasia in patients with isolated cranial neuropathies.

PMID- 14962439
TI  - Intravitreal triamcinolone acetonide for treatment of sympathetic ophthalmia.
AB  - PURPOSE: To report on the treatment of long-standing sympathetic ophthalmia by
      intravitreal triamcinolone acetonide. DESIGN: Clinical interventional case
      report. METHODS: A 47-year-old patient who suffered from sympathetic ophthalmia
      and who was treated with intensive systemic immunosuppressive therapy received an
      intravitreal injection of 25 mg of triamcinolone acetonide. Before injection,
      intraocular pressure ranged between 5 and 8 mm Hg; visual acuity measured 6/20.
      RESULTS: Within the first 4 weeks after the injection, visual acuity improved
      from 6/20 to 6/12, intraocular pressure increased to values between 10 mm Hg and
      13 mm Hg, and intraocular flare measurements decreased by approximately 50%.
      Systemic immunosuppressive treatment was reduced to 10 mg prednisolone/day at the
      first postoperative day and could not be stopped due to an adrenal insufficiency.
      Three months after the injection, visual acuity regressed to 6/20, intraocular
      pressure was reduced to values between 5 mm Hg and 10 mm Hg, and anterior chamber
      flare increased. The patient received a second intravitreal injection of 25 mg of
      triamcinolone acetonide after which intraocular pressure increased again to
      values between 10 mm and 13 mm Hg, and anterior chamber flare decreased. After
      the injection, perimetry revealed a marked enlargement of the originally
      constricted visual field with a decrease in mean visual field defect from
      approximately 11 dB to values lower than 7 dB. CONCLUSIONS: Intravitreal
      injections of triamcinolone acetonide may be an additional tool in the treatment
      for sympathetic ophthalmia.

PMID- 14962440
TI  - Nodular scleritis and panuveitis with erythema elevatum diutinum.
AB  - PURPOSE: To report a case of nodular scleritis and panuveitis associated with
      erythema elevatum diutinum, a rare immunocomplex-mediated skin disease. DESIGN:
      Observational case report. METHODS: A 22-year-old woman who was diagnosed with
      erythema elevatum diutinum developed nodular scleritis and panuveitis of the
      right eye. She had experienced peripheral ulcerative keratitis with corneal
      perforation. RESULTS: All other known causes of nodular scleritis and panuveitis
      were investigated and ruled out. CONCLUSIONS: Erythema elevatum diutinum should
      be considered as an underlying systemic disease associated with nodular scleritis
      and panuveitis as well as peripheral keratitis.

PMID- 14962441
TI  - Ocular pythiosis: is it under-diagnosed?
AB  - PURPOSE: To increase awareness of ocular pythiosis by presenting a typical case
      and summarizing clinical data of 11 ocular pythiosis cases in Ramathibodi
      Hospital. DESIGN: Interventional case report. METHODS: A 48-year-old healthy
      woman with a history of 3-week painful corneal ulcer of left eye was treated with
      enucleation. RESULTS: The histopathology of enucleated eye revealed
      endophthalmitis and ulcerative keratitis with numerous hyphae in full-thickness
      of corneal stroma. The culture identification of the causative organism was
      Pythium insidiosum. The final diagnosis was ocular pythiosis. CONCLUSIONS:
      Pythium insidiosum is a causative agent of pythiosis and is distributed
      worldwide. Ocular pythiosis may not be uncommon, as it may be underdiagnosed due
      to unfamiliarity among clinicians and microbiologists. Diagnosis of pythiosis is
      difficult. The disease has high morbidity, as evidenced by nearly evisceration or
      enucleation among all patients at Ramathibodi Hospital. Early detection and
      effective treatment are needed for possible cure.

PMID- 14962442
TI  - Responsiveness of the SF-36 health survey to changes in visual acuity among
      patients with subfoveal choroidal neovascularization.
AB  - PURPOSE: To report the responsiveness of the SF-36 Health Survey to changes in
      visual acuity among patients with subfoveal choroidal neovascularization
      participating in the Submacular Surgery Trials pilot study. DESIGN: Cohort study.
      METHODS: Correlation analyses were used to explore relationships at each time
      point, and linear regression was used to determine the relation between the 2
      year changes in SF-36 scores and visual acuity. RESULTS: A weak, but
      statistically significant, association was found between the 2-year changes in
      both the Physical Component Summary score and the Physical Functioning subscale
      with changes in visual acuity of the better eye. No association was found between
      changes in visual acuity and the Mental Component Summary score or the Mental
      Health subscale. CONCLUSIONS: The SF-36 summary scales and the individual
      subscales were minimally responsive to 2-year changes in visual acuity in this
      subgroup of patients.

PMID- 14962444
TI  - Migration of lens epithelial cells through haptic root of single-piece acrylic
      foldable intraocular lens.
AB  - PURPOSE: To report a case of posterior capsule opacification after cataract
      surgery due to lens epithelial cell migration through the haptic root of a single
      piece acrylic-foldable intraocular lens. DESIGN: Interventional case report.
      METHODS: A 60-year-old man with senile cataract underwent phacoemulsification and
      implantation of single-piece acrylic intraocular lens having thick and wide
      haptic loops. RESULTS: There were no operative or short-term postoperative
      complications, and patient's visual acuity was 20/20 on the day following
      surgery. At 19 months postoperatively, we observed posterior capsule opacity
      extending from the base of the intraocular lens loops. CONCLUSION: Broad and
      thick haptic root can be a path through which lens epithelial cells migrate
      toward the center of the posterior capsule, forming posterior capsule
      opacification.

PMID- 14962443
TI  - Thirty-year follow-up of a patient with leber congenital amaurosis and novel
      RPE65 mutations.
AB  - PURPOSE: To present long-term follow-up on a North American patient with Leber
      congenital amaurosis (LCA) and novel compound heterozygous mutations in the RPE65
      gene. DESIGN: Case report. METHODS: RPE65 mutation screening and search for
      sequence changes using Single Strand Conformation Polymorphism and direct DNA
      sequencing. Ophthalmic examination and electrophysiologic testing. RESULTS: A 35
      year-old female carried two RPE65 mutations: a maternal 961A>T (K303X) nonsense
      mutation and a paternal 1346A>G (Y431C) missense mutation. She had severe visual
      deficits and an absence of rod and cone Electroretinogram responses. Visual
      acuity of 20/60 both eyes and normal color recognition during early childhood
      declined to 2/200 in the right eye and 1/200 in the left eye at the age of 35.
      CONCLUSIONS: The RPE65 mutations K303X and Y431C in compound heterozygous form
      cause progressive visual compromise that starts in childhood and advances to
      severe visual loss by the fourth decade of life.

PMID- 14962445
TI  - Microwave-superheated Vics Vapo Rub: an ocular public health danger.
AB  - PURPOSE: To report a case of a microwave-oven superheated petroleum-based liquid
      causing severe chemical and thermal ocular burns treated successfully with
      amniotic membrane transplantation. DESIGN: Observational case report. METHODS:
      Retrospective review of clinical case. RESULTS: A 77-year-old woman sustained a
      severe combined chemical and thermal burn from microwave-heated Vicks Vapo-Rub
      requiring amniotic membrane transplant, with subsequent development of
      phacomorphic glaucoma, requiring cataract extraction, and bullous keratopathy,
      requiring penetrating keratoplasty. CONCLUSIONS: As microwave oven use becomes
      more commonplace, the risk of superheating liquids becomes an increasingly
      significant ocular danger. Continued efforts to educate the public about safe
      microwave use is necessary. Additionally, amniotic membrane transplantation was
      found to be effective in managing a combined chemical and thermal ocular burn.

PMID- 14962446
TI  - Intraocular pressure asymmetry and undiagnosed open-angle glaucoma in an older
      population.
AB  - PURPOSE: To quantify prevalence of asymmetric intraocular pressure (IOP) and
      assess associations with undiagnosed open-angle glaucoma. DESIGN: Population
      based cross-sectional study. METHODS: Participants underwent applanation
      tonometry. Intraocular pressure asymmetry was defined for differences > or = 3 mm
      Hg; open-angle glaucoma was diagnosed if glaucomatous optic disk and field
      changes were congruous. Analyses excluded subjects using glaucoma medication,
      known glaucoma, pseudoexfoliation, and cataract surgery. RESULTS: Intraocular
      pressure asymmetry was present in 5.1% of subjects and was greater for patients
      older than 70 years (6.2%). Of subjects with maximum IOP > 21 mm Hg, IOP
      asymmetry was present in 41.1%. Undiagnosed open-angle glaucoma was more frequent
      among subjects with (4.8%) than without (1.2%) IOP asymmetry. This relationship
      remained significant for maximum IOP < or = 21 mm Hg. CONCLUSIONS: Intraocular
      pressure asymmetry may be a useful sign of undiagnosed glaucoma in subjects
      without elevated IOP.

PMID- 14962448
TI  - Selective occlusion of subfoveal choroidal neovascularization in pathologic
      myopia using a new technique of ingrowth site treatment.

PMID- 14962449
TI  - Reduced concentration and incubation of intravitreal indocyanine green can
      improve the functional outcome in macular hole surgery.

PMID- 14962451
TI  - A comparison of latanoprost, bimatoprost, and travoprost in patients with
      elevated intraocular pressure: a 12-week, randomized, masked-evaluator,
      multicenter study.

PMID- 14962468
TI  - Myocardial reperfusion injury: a new view.

PMID- 14962469
TI  - The first minutes of reperfusion: a window of opportunity for cardioprotection.
AB  - During the past decade, the understanding has grown that control of the
      conditions of reperfusion is critical for salvaging ischemic-reperfused
      myocardium. The first few minutes of reperfusion constitute a critical phase, as
      here lethal tissue injury in addition to that already developed during ischemia
      may be initiated. The identification of the mechanisms of reperfusion-induced
      cell death opens a new window of opportunity for cardioprotection in the clinic.
      Development of cardiomyocyte hypercontracture is a predominant feature of
      reperfusion injury. We and others have shown that control of hypercontracture in
      reperfusion reduces the extent of tissue injury. On the cellular level, it was
      shown that reperfusion-induced hypercontracture might either originate from a
      rigor-type mechanism, when energy recovery proceeds very slowly, or from Ca2+
      overload, when energy recovery is rapid but cytosolic Ca2+ load is high. These
      two mechanisms can be influenced by various interventions that either connect
      with cytosolic Ca2+ control or myofibrillar Ca2+ sensitivity or with
      mitochondrial energy production. These experimental approaches will hopefully
      lead to novel strategies for clinical cardioprotection during the early phase of
      reperfusion.

PMID- 14962470
TI  - Mitochondrial permeability transition pore opening during myocardial reperfusion-
      a target for cardioprotection.
AB  - Reperfusion of the heart after a period of ischaemia leads to the opening of a
      nonspecific pore in the inner mitochondrial membrane, known as the mitochondrial
      permeability transition pore (MPTP). This transition causes mitochondria to
      become uncoupled and capable of hydrolysing rather than synthesising ATP.
      Unrestrained, this will lead to the loss of ionic homeostasis and ultimately
      necrotic cell death. The functional recovery of the Langendorff-perfused heart
      from ischaemia inversely correlates with the extent of pore opening, and
      inhibition of the MPTP provides protection against reperfusion injury. This may
      be mediated either by a direct interaction with the MPTP [e.g., by Cyclosporin A
      (CsA) and Sanglifehrin A (SfA)], or indirectly by decreasing calcium loading and
      reactive oxygen species (ROS; key inducers of pore opening) or lowering
      intracellular pH. Agents working in this way may include pyruvate, propofol,
      Na+/H+ antiporter inhibitors, and ischaemic preconditioning (IPC). Mitochondrial
      KATP channels have been implicated in preconditioning, but our own data suggest
      that the channel openers and blockers used in these studies work through
      alternative mechanisms. In addition to its role in necrosis, transient opening of
      the MPTP may occur and lead to the release of cytochrome c and other proapoptotic
      molecules that initiate the apoptotic cascade. However, only if subsequent MPTP
      closure occurs will ATP levels be maintained, ensuring that cell death continues
      down an apoptotic, rather than a necrotic, pathway.

PMID- 14962471
TI  - Gap junction-mediated spread of cell injury and death during myocardial ischemia
      reperfusion.
AB  - Gap junction-mediated intercellular communication (GJMIC) has been known for a
      long time to be essential in propagation of electrical impulse in the heart, and
      the contribution of altered GJMIC to the genesis of arrhythmias has been
      extensively investigated. However, although it is well known that GJMIC allows
      the exchange of biologically important molecules between adjacent cells, the
      pathophysiological significance of such chemical coupling during myocardial
      ischemia and reperfusion is much less known. It has been solidly established that
      ischemia impairs GJMIC and eventually leads to electrical uncoupling, but recent
      studies suggest that GJMIC may still allow synchronization of the onset of
      ischemic rigor contracture and of the progression of ischemic injury beyond rigor
      onset. During reperfusion, GJMIC has been shown to mediate cell-to-cell
      propagation of hypercontracture and cell death, and there is evidence that this
      phenomenon explains the continuity of areas of contraction band necrosis and
      contributes to final infarct size. Finally, there is increasing evidence that GJ
      or their protein components are involved in the genesis of the protective effect
      of ischemic preconditioning, although probably through mechanisms independent
      from modulator of GJMIC. GJ play an important role in the pathophysiology of cell
      injury and death during myocardial ischemia-reperfusion and are potential targets
      for new cardioprotective therapeutic strategies.

PMID- 14962472
TI  - Nitric oxide in myocardial ischemia/reperfusion injury.
AB  - Administration of nitric oxide (NO), NO donors or drugs that enhance NO release
      (statins, calcium antagonists, ACE-inhibitors, dexamethasone) prior to ischemia
      protects the myocardium against ischemia/reperfusion injury. While this exogenous
      administration of NO prior to ischemia can initiate a preconditioning-like
      phenomenon, endogenous NO-synthase (NOS)-derived NO is not involved in triggering
      or mediating the early phase of ischemic preconditioning's protection, but does
      play a pivotal role for initiating and mediating the delayed phase of ischemic
      preconditioning's protection. The present review now summarizes the importance of
      endogenous and exogenous NO when given at the time of reperfusion for vascular
      and myocardial function and morphological outcome following ischemia/reperfusion.
      Given the inconsistency of the published data, potential confounding factors that
      might affect experimental results on the role of NO in myocardial
      ischemia/reperfusion were identified, such as (1) the lack of characterization of
      the involved NOS isoforms in myocardial ischemia/reperfusion injury in different
      animal species, (2) the lack of direct measurements of myocardial NO
      concentration and/or NOS activity to assure sufficient NOS inhibition, (3) the
      lack of consideration of nonenzymatic NO production as a potential source of NO,
      and (4) the absence of plasma or blood components in in vitro studies influencing
      NO delivery and metabolism. Future research on the importance of NO in
      ischemia/reperfusion injury will have to focus more precisely on the
      identification and standardization of potential confounding experimental factors
      that influence synthesis, transport, and interaction of NO with various targets
      in blood and tissue.

PMID- 14962473
TI  - Role of apoptosis in reperfusion injury.
AB  - Many changes occur during reperfusion of the myocardium after ischemic damage.
      Necrosis and apoptosis appear to be ongoing during ischemia, while apoptosis is
      boosted by the reperfusion event. In the past 10 years, distinct intracellular
      pathways important for hypertrophy, apoptosis, cardiac failure, ischemic
      preconditioning and reperfusion damage have been recognized. The eventual
      response of the cardiomyocyte will depend on energy and time available as well as
      changes in pH and ion handling and the delicate balance of activation of
      signaling molecules and transcription factors. There is agreement on the central
      role of mitochondria and nitric oxide (NO) in programmed cell death. However,
      although many groups analyzed the contribution of NO to cell death, still the
      circumstances and levels required for cardioprotection or death are unclear.
      Growth factors, cytokines, and downstream signaling molecules have been shown to
      influence programmed cell death through mechanisms reminiscent of
      preconditioning. Here, the role of apoptosis in ischemia reperfusion-related cell
      death is reviewed. Important data have been obtained in isolated cells, intact
      hearts and intact animals. Both pharmacological as well as genetic interventions
      are discussed. Proof for apoptosis in man post-myocardial infarction (MI) treated
      through primary Percutaneous Trans-luminal Coronary Angioplasty or other
      reperfusion therapy is reviewed. Finally, the currently available quantification
      methods for apoptosis post-MI are mentioned.

PMID- 14962474
TI  - Protein kinase activation and myocardial ischemia/reperfusion injury.
AB  - Myocardial ischemia and ischemia/reperfusion activate several protein kinase
      pathways. Protein kinase activation potentially regulates the onset of myocardial
      cell injury and the reduction of this injury by ischemic and pharmacologic
      preconditioning. The primary protein kinase pathways that are potentially
      activated by myocardial ischemia/reperfusion include: the MAP kinases, ERK 1/2,
      JNK 1/2, p38 MAPKalpha/beta; the cell survival kinase, Akt; and the sodium
      hydrogen exchanger (NHE) kinase, p90RSK. The literature does not support a role
      for ischemia/reperfusion in the activation of the tyrosine kinases, Src and Lck,
      or the translocation and activation of PKC. This review will detail the role of
      these protein kinases in the onset of myocardial cell death by necrosis and
      apoptosis and the reduction of this injury by preconditioning.

PMID- 14962475
TI  - Molecular determinants of responses to myocardial ischemia/reperfusion injury:
      focus on hypoxia-inducible and heat shock factors.
AB  - During the past several years much new evidence has accumulated regarding the
      molecular and biochemical mechanisms underlying cardiac responses to hypoxia and
      to ischemia/reperfusion injury. Studies have involved cell culture, and ex vivo
      and in vivo preparations. This review focuses on regulation of two transcription
      factors that are thought to be important in these processes, hypoxia-inducible
      factor1alpha (HIF-1alpha) and heat shock factor (HSF). Both of these molecules
      are expressed acutely and chronically in response to hypoxia and
      ischemia/reperfusion, and both have numerous targets that comprise part of
      integrated response to ischemic injury aimed at promoting cell survival. Emphasis
      is placed on new mechanisms of action that regulate HIF-1alpha, HSF, and heat
      shock proteins as key responses to hypoxia and ischemia, and possible approaches
      to therapy based on these data are discussed.

PMID- 14962476
TI  - New directions for protecting the heart against ischaemia-reperfusion injury:
      targeting the Reperfusion Injury Salvage Kinase (RISK)-pathway.
AB  - Reperfusion is a pre-requisite to salvaging viable myocardium, following an acute
      myocardial infarction. Reperfusion of ischaemic myocardium, however, is not
      without risk, as the act of reperfusion itself can paradoxically result in
      myocyte death: a phenomenon termed lethal reperfusion-induced injury. Therapeutic
      strategies that target and attenuate reperfusion-induced cell death may provide
      novel pharmacological agents, which can be used as an adjunct to current
      reperfusion therapy, to limit myocardial infarction. Recent evidence has
      implicated apoptotic cell death during the phase of reperfusion as an important
      contributor to lethal reperfusion-induced injury. Targeting anti-apoptotic
      mechanisms of cellular protection at the time of reperfusion may therefore offer
      a potential approach to attenuating reperfusion-induced cell death. In this
      regard, ischaemia-reperfusion has been shown to activate the anti-apoptotic pro
      survival kinase signalling cascades, phosphatidylinositol-3-OH kinase (PI3K)-Akt
      and p42/p44 extra-cellular signal-regulated kinases (Erk 1/2), both of which have
      been implicated in cellular survival. Activating these pro-survival kinase
      cascades at the time of reperfusion has been demonstrated to confer protection
      against reperfusion-induced injury. We and others have shown that insulin,
      insulin-like growth factor-1 (IGF-1), transforming growth factor-beta1 (TGF
      beta1), cardiotrophin-1 (CT-1), urocortin, atorvastatin and bradykinin protect
      the heart, by activating the PI3K-Akt and/or Erk 1/2 kinase cascades, when given
      at the commencement of reperfusion, following a lethal ischaemic insult.
      Pharmacological manipulation and up-regulation of these pro-survival kinase
      cascades, which we refer to as the Reperfusion Injury Salvage Kinase (RISK)
      pathway, as an adjunct to reperfusion may therefore protect the myocardium from
      lethal reperfusion-induced cell death and provide a novel strategy to salvaging
      viable myocardium and limiting infarct size.

PMID- 14962477
TI  - New concepts in reactive oxygen species and cardiovascular reperfusion
      physiology.
AB  - Increasingly complex behavior of free radicals and reactive oxygen species (ROS)
      are noted within biological systems. Classically free radicals and ROS were
      considered injurious, however current mechanisms describe both protective and
      deleterious effects. A burst of ROS has been well described with the first
      moments of reperfusion and is associated with injury. However ROS can also be
      protective as signal preconditioning protection and induce stress responses that
      lead to survival. ROS generation is appreciated to occur during ischemia despite
      the low oxygen tension, from a likely mitochondria source, and ROS-induced ROS
      release may amplify its signal. The burst of ROS seen during reperfusion may
      originate from a different cellular source than during ischemia and is not yet
      fully identified. ROS and cellular redox conditions regulate a large number of
      vital pathways (energy metabolism, survival/stress responses, apoptosis,
      inflammatory response, oxygen sensing, etc). While cellular systems may
      demonstrate reperfusion injury, whole organ and animal models continue to report
      contradictory results on reperfusion injury and the role of antioxidants as a
      therapy. Collectively, these data may offer insight into why clinical trials of
      antioxidants have had such mixed and mostly negative results. Future antioxidant
      therapies are likely to be effective but they must become: more specific for site
      of action, not have deleterious effects on other signaling pathways, be targeted
      to a specific reactive oxygen species or cellular compartment, and be "time
      sensitive" so they deliver the correct therapy at precisely the correct time in
      ischemia and reperfusion.

PMID- 14962478
TI  - Poly(ADP-ribose) polymerase activation in the reperfused myocardium.
AB  - The activation of poly(ADP-ribose) polymerase (PARP) is now considered a final
      common effector in various types of tissue injury including systemic
      inflammation, circulatory shock and ischemia/reperfusion. Free radical and
      oxidant production and related cytotoxicity during ischemia/reperfusion leads to
      DNA strand breakage which activates the nuclear enzyme PARP and initiates an
      energy-consuming, inefficient cellular metabolic cycle with transfer of the ADP
      ribosyl moiety of NAD+ to protein acceptors. During the last 5 years, a growing
      number of experimental studies demonstrated the beneficial effects of PARP
      inhibition in cell cultures through rodent models and more recently in pre
      clinical large animal models of regional and global ischemia/reperfusion injury.
      The objective of the current review is to provide an overview of the experimental
      evidence implicating PARP as a pathophysiological modulator of myocardial injury
      in vitro and in vivo.

PMID- 14962479
TI  - Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion
      injury.
AB  - Neutrophils respond to myocardial ischemia-reperfusion in a manner similar to the
      bacterial invasion of a host. The inflammatory-like response that follows the
      onset of reperfusion involves intense interactions with the coronary vascular
      endothelium, arterial wall, and cardiomyocytes in a very well-choreographed
      manner. Neutrophils have been implicated as primary and secondary mediators of
      lethal injury after reperfusion to coronary vascular endothelium and
      cardiomyocytes. The involvement of neutrophils in the pathogenesis of lethal
      myocardial injury has been inferred from (1) their presence and accumulation in
      reperfused myocardium in temporal agreement with injury induced, (2) the
      armamentarium of toxic agents such as oxidants and proteases that are released by
      neutrophils in reperfused myocardium, (3) responsivity to (recruitment by and/or
      activation by) inflammatory factors released by reperfused myocardium, and (4)
      inhibition of lethal post-ischemic myocyte or endothelial cell injury by
      strategies that interdict neutrophil interactions at any number of stages.
      However, whether neutrophils are directly involved in the pathogenesis of lethal
      reperfusion injury in the myocardium, are just pedestrian (first) responders to
      inflammatory signals released after the onset of reperfusion, or are important to
      an early but not clinically important phase of pathology are still points of
      controversy. As with the general area of myocardial protection itself, the
      failure to reproduce the salubrious effects of anti-neutrophil therapeutic
      strategies and to successfully translate these strategies into clinical practice
      has not only fueled the debate, but has jeopardized the further pursuit of
      myocardial protection therapeutics to improve post-ischemic outcomes. This review
      will describe the molecular responses of neutrophils to ischemia-reperfusion,
      discuss the cellular and tissue damage inflicted either directly or indirectly by
      these white cells, and discuss the physiological impact of interdiction of
      neutrophil-mediated interactions with myocardial cells at various levels on
      lethal post-ischemic injury. In addition, it will discuss the arguments for and
      against the involvement of neutrophils in responses to ischemia-reperfusion in
      experimental models, and the failure to translate experimentally successful
      therapy into clinical practice.

PMID- 14962480
TI  - Role of platelets in coronary thrombosis and reperfusion of ischemic myocardium.
AB  - Platelet-dependent thrombus formation is a key event in the pathogenesis of acute
      myocardial infarction (AMI). Platelets mediate both thrombotic occlusion of the
      entire epicardial coronary artery and also accumulate in the microcirculation
      resulting in impairment of microcirculation and provoking myocardial ischemia
      during reperfusion. In the past, our understanding of platelet function in
      myocardial infarction (MI) and reperfusion has extended substantially resulting
      in development of novel and clinically effective treatment strategies. This
      review summarizes the mechanisms of coronary thrombosis and consequences of
      platelet accumulation in reperfused myocardium. Basic pathophysiological
      mechanisms of platelet adhesion and secretion are reviewed first, followed by the
      description of the molecular steps involved in platelet-mediated thrombus
      formation around an atherosclerotic plaque. Next, the role of platelets in
      inflammation is summarized with the focus on platelet-endothelium and platelet
      leukocyte interactions.

PMID- 14962481
TI  - Role of clinical pathologies in myocardial injury following ischaemia and
      reperfusion.
AB  - The myocardial injury that occurs following a period of ischaemia and reperfusion
      is well recognised and the underlying mechanisms have been extensively
      investigated in healthy myocardial tissues; however, the influence of the risk
      factors associated with cardiovascular diseases on ischaemia/reperfusion injury
      remains unclear. In this article, the present knowledge on how clinical
      pathologies such as diabetes, hypercholesterolaemia, hypertension, myocardial
      hypertrophy and heart failure may influence ischaemia/reperfusion injury of the
      heart and the potential mechanisms involved are reviewed.

PMID- 14962482
TI  - Limited effects of post-ischemic NHE blockade on [Na+]i and pHi in rat hearts
      explain its lack of cardioprotection.
AB  - OBJECTIVE: Na+/H+ exchanger (NHE) blockade fails as reperfusion therapy in
      patients with acute myocardial infarction. In experimental studies, the reports
      on the efficacy of NHE blockade only during reperfusion are inconsistent.
      Differences in the severity of ischemia and in drug delivery may explain these
      inconsistencies. Little is known about the primary goal of post-ischemic NHE
      blockade, i.e. reduction of Na+i overload. METHODS: Isolated rat hearts were
      subjected either to 60 min of low flow (0.2 ml/min) ischemia or 25 min of zero
      flow ischemia. Hearts were reperfused with or without the selective NHE blocker
      cariporide added to the perfusate. [Na+]i and pHi were measured with simultaneous
      23Na and 31P NMR spectroscopy. RESULTS: After 60 min of low flow ischemia [Na+]i
      had risen to 424 +/- 14% of baseline and pHi was 6.36 +/- 0.03. After low flow
      ischemia [Na+]i and pHi recovered similarly in treated and untreated hearts.
      Recovery of the rate pressure product (RPP) was poorly in both groups. After 25
      min of zero flow ischemia [Na+]i had risen to 279 +/- 7% of baseline and pHi was
      6.12 +/- 0.02. NHE blockade after zero flow ischemia caused [Na+]i to decrease
      during the first 30 s of reperfusion, followed by a partial and transient rise
      during the second 30 s. Untreated hearts showed a very small rise in [Na+]i
      during the first minute. pHi recovered 30 s slower in cariporide treated hearts
      than in untreated hearts (p<0.05). No effect of cariporide on RPP could be
      detected since RPP recovered fully in untreated hearts. The end diastolic
      pressure, however, was increased during reperfusion to a similar extent in both
      groups. CONCLUSION: The lack of cardioprotection under these specific conditions
      of zero flow and low flow ischemia can be explained by the fact that NHE blockade
      only resulted in a small and transient effect on [Na+]i and pHi.

PMID- 14962483
TI  - Selective retroinfusion of GSH and cariporide attenuates myocardial ischemia
      reperfusion injury in a preclinical pig model.
AB  - OBJECTIVE: Reperfusion after ischemia may contribute to loss of myocardial
      function and increase in infarct size. Scavenging of reactive oxygen species
      (ROS) by glutathione (GSH) and inhibition of the sodium-proton-exchanger by
      cariporide are both capable of reducing myocardial reperfusion injury. We tested
      the efficacy of both agents applied regionally into the myocardium immediately
      before reperfusion. METHODS: Neonatal rat cardiomyocytes (NRCMs) were exposed to
      either hypoxia (H, 8 h)/reoxygenation (R, 1 h) or H2O2 (300 microM) in the
      presence or absence of GSH (10 mg/ml). In pigs (n=5 per group), percutaneous LAD
      occlusion was performed for 60 min. Application of GSH (250 mg/kg) and/or
      cariporide (1 mg/kg) was achieved by pressure-regulated retroinfusion of the
      anterior cardiac vein draining the ischemic area starting 5 min before reopening
      of the occluded LAD. Seven days later, subendocardial segment shortening (SES)
      was analyzed by sonomicrometry. Infarct size was determined by methylene-blue
      staining of the non-ischemic area and tetrazolium red staining of the viable
      myocardium in the area at risk (AAR). RESULTS: NRCM incubated with GSH (10 mg/ml)
      survived H/R or H2O2 (0.3 mM) to a larger extent than untreated cells. In pigs,
      infarct size of untreated hearts (51 +/- 6% of the AAR) was not significantly
      altered by GSH or cariporide retroinfusion alone (41 +/- 3% and 42 +/- 6%). In
      contrast, combined retroinfusion of cariporide and GSH significantly reduced
      infarct size (29 +/- 3%). SES of the infarcted area was improved only after
      cariporide/GSH retroinfusion as compared to untreated hearts. Additional systemic
      application of CD18-antibody IB4 (1.5 mg/kg) did not alter infarct size or SES in
      comparison to GSH/cariporide retroinfusion alone. CONCLUSION: Timely application
      of GSH scavenging ROS and cariporide targeting ion imbalance provides
      cardioprotection to the postischemic heart, which is superior to either treatment
      alone. The lack of an effect of additional IB4 treatment may indicate that
      GSH/cariporide retroinfusion itself affects leukocyte-dependent reperfusion
      injury.

PMID- 14962484
TI  - Modulating Toll-like receptor mediated signaling by (1-->3)-beta-D-glucan rapidly
      induces cardioprotection.
AB  - OBJECTIVE: Immune and inflammatory signaling pathways, initiated by the innate
      response, are involved in myocardial ischemia/reperfusion (I/R) injury. Toll-like
      receptor (TLR) mediated MyD88-dependent NFkappaB pathways play a role in the
      induction of innate immunity. We have reported that glucan phosphate (GP)
      improved survival in experimental sepsis, which correlated with decreased tissue
      NFkappaB activation. In the present study, we report that GP rapidly induced
      cardioprotection against I/R injury in vivo. METHODS: Sprague-Dawley rats were
      pretreated with GP (40 mg/kg, i.p) 1 h before 45 min of ligation of the left
      anterior descending coronary followed by reperfusion for 4 and 24 h. Infarction
      size was examined by triphenyltetrazolium chloride (TTC) staining. NFkappaB
      activation was analyzed by electrophoretic mobility shift assay (EMSA). IkappaB
      kinase-beta (IKKbeta), IL-1 receptor-associated kinase (IRAK) and
      Phosphoinositide 3-kinase (PI3K) activities were determined by kinase assay with
      appropriate substrates. Association of TLR4 with MyD88 or with PI3K p85 was
      assessed by immunoprecipitation with anti-TLR4 followed by immunoblotting with
      anti-MyD88 or anti-p85. RESULTS: GP treatment reduced infarct size by 47% in rat
      hearts subjected to reperfusion for 4 h and by 50% following reperfusion for 24
      h. The same protective effect was observed when GP was administrated 5 min after
      initiation of ischemia. The mechanisms of GP induced cardioprotection involve
      decreased association of TLR4 with MyD88, inhibition of I/R induced IRAK and
      IKKbeta activity and decreased NFkappaB activity. In addition, GP increased TLR4
      phosphotyrosine, resulting in increasing PI3K/Akt activity in the myocardium,
      which correlated with decreased cardiac myocyte apoptosis following I/R.
      CONCLUSION: The results suggest that activation of the TLR mediated MyD88
      dependent NFkappaB signaling pathway may play an important role in myocardial I/R
      injury, while stimulation of the PI3K/Akt signaling could serve a protective
      role. The data indicates that GP treatment shifts the TLR mediated activation
      signal in I/R from a predominantly NFkappaB pathway to a predominant PI3K/Akt
      signaling pathway.

PMID- 14962485
TI  - Inhibition of Rho-kinase protects the heart against ischemia/reperfusion injury.
AB  - OBJECTIVE: To investigate the role of Rho A and Rho-kinase in acute myocardial
      ischemia/reperfusion injury and the protective effect of Rho-kinase inhibitor, Y
      27632 [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)cyclohexanecarboxamide].
      METHODS AND RESULTS: Male CD1 mice were subjected to 30 min of coronary occlusion
      and 24 h reperfusion. Ischemia/reperfusion upregulated expression of Rho A in
      ischemic myocardium, and subsequently activated Rho-kinase. Y-27632 significantly
      inhibited the activation of Rho-kinase following ischemia/reperfusion. Treatment
      with Y-27632 at 10 and 30 mg/kg oral administration, reduced infarct size by
      30.2% and 41.1%, respectively (P<0.01 vs. vehicle). Y-27632 also enhanced post
      ischemia cardiac function. Left ventricular systolic pressure, +dP/dt and -dP/dt
      were significantly improved by 23.5%, 52.3%, and 59.4%, respectively (P<0.01 vs.
      vehicle). Moreover, Y-27632 reduced ischemia/reperfusion-induced myocardial
      apoptosis. The apoptotic myocytes in ischemic myocardium after 4 h reperfusion
      were reduced from 13.1% in vehicle group to 6.4% in Y-27632-treated group
      (P<0.01). Meanwhile, ischemia/reperfusion-induced downregulation of Bcl-2 in
      myocardium was remarkably attenuated in the treated animals. Ischemia/reperfusion
      resulted in remarkable elevation in serum levels of proinflammatory cytokines,
      interleukin-6 (IL-6), keratinocyte chemoattractant (KC) and granulocyte colony
      stimulating factor (G-CSF), which was significantly suppressed by Y-27632. In
      addition, Y-27632 decreased ischemia/reperfusion-induced accumulation of
      neutrophils in the heart by 45% (P<0.01). CONCLUSIONS: These results suggest that
      Rho-kinase plays a pivotal role in myocardial ischemia/reperfusion injury. The
      cardiac protection provided by treatment with a selective Rho-kinase inhibitor is
      likely via anti-apoptotic effect and attenuation of ischemia/reperfusion-induced
      inflammatory responses. The finding of this study suggest a novel therapeutic
      approach to the treatment of acute myocardial ischemia/reperfusion injury.

PMID- 14962486
TI  - The bradykinin B1 receptor contributes to the cardioprotective effects of AT1
      blockade after experimental myocardial infarction.
AB  - OBJECTIVE: To investigate the role of the bradykinin B1 receptor (B1R) on the
      angiotensin receptor AT1 blockade-dependent cardioprotective effects, we studied
      the B1R regulation in wild-type rats treated with the AT1 antagonist, irbesartan
      (IRB), and also in transgenic rats with cardiac overexpression of the human AT1
      (TGR-alphaMHCAT1) after induction of myocardial infarction (MI). In addition, we
      treated wild-type rats with IRB and/or the B1R antagonist, B9958, and determined
      the left ventricular (LV) function. METHODS: Untreated, IRB (50 mg/kg/day/p.o.),
      B9958 (0.1 mg/kg/48 h/s.c.), and IRB/B9958-treated Sprague-Dawley rats were
      submitted to a permanent occlusion of the left descending coronary artery. Six
      days and three weeks after induction of MI, the LV function was characterized by
      using a Millar-tip catheter. Myocardial AT1- and B1-mRNA expression were analyzed
      by RNase-protection assays, B1R protein density by immunohistochemistry. RESULTS:
      At both time points, LV function had improved by almost 50% after treatment with
      IRB but remained unchanged in TGR-alphaMHCAT1 after induction of MI compared to
      their untreated controls. The beneficial effect of IRB was reversed by co
      treatment with B9958. The B1R antagonist treatment alone had no effect. A cross
      talk between AT1 and B1R was also indicated by an up-regulation of B1R after
      treatment with IRB on protein and RNA level, while AT1 overexpression reduced B1R
      expression after induction of MI. CONCLUSION: These results indicate that the
      mechanisms of B1R regulation are influenced by the AT1 receptor. Thus, we are
      able to demonstrate for the first time that the B1R contributes to the cardio
      beneficial effects of AT1 blockade.

PMID- 14962487
TI  - Diazoxide causes early activation of cardiac sarcolemmal KATP channels during
      metabolic inhibition by an indirect mechanism.
AB  - OBJECTIVE: We have used isolated myocytes to investigate the effects of diazoxide
      on sarcolemmal KATP channel (sarcoKATP) activity and action potential failure
      during metabolic inhibition, and the role of these channels in protection of
      functional recovery on reperfusion. MATERIALS AND METHODS: Isolated adult rat
      ventricular myocytes were exposed to metabolic inhibition (NaCN and iodoacetate)
      and reperfusion. Functional recovery was assessed from the ability of cells to
      contract on electrical stimulation and to recover calcium homeostasis, measured
      with fura-2. Action potentials and KATP currents were measured using patch clamp.
      RESULTS: Pretreatment with diazoxide (100 microM, 5 min) increased the proportion
      of cells that recovered contractile function after MI and reperfusion from 16.8
      +/- 2.4% to 65.0 +/- 2.2% (p<0.001) and the proportion of cells in which [Ca2+]i
      recovered to <250 nM. Pretreatment also accelerated action potential and
      contractile failure during MI. In cell-attached patches, MI activated sarcoKATP
      channels after 224 +/- 11 s, and diazoxide pretreatment decreased this to 145 +/-
      24 s (p<0.01). However, diazoxide present in the patch pipette did not accelerate
      sarcoKATP channel activation. Intracellular Mg2+ rose earlier in diazoxide
      pretreated cells. The sarcoKATP blocker HMR 1883 delayed action potential failure
      and reduced diazoxide protection. CONCLUSIONS: Diazoxide pretreatment increases
      recovery of function and [Ca2+]i following reperfusion. Protection is coupled
      with early action potential failure, due to early activation of sarcoKATP
      channels during metabolic inhibition (MI), which is likely to involve an indirect
      effect of diazoxide.

PMID- 14962488
TI  - Reduced reactive O2 species formation and preserved mitochondrial NADH and [Ca2+]
      levels during short-term 17 degrees C ischemia in intact hearts.
AB  - OBJECTIVE: Different cardioprotective strategies such as ischemic or
      pharmacologic preconditioning lead to attenuated ischemia/reperfusion (I/R)
      injury with less mechanical dysfunction and reduced infarct size on reperfusion.
      Improved mitochondrial function during ischemia as well as on reperfusion is a
      key feature of cardioprotection. The best reversible cardioprotective strategy is
      hypothermia. We investigated mitochondrial protection before, during, and after
      hypothermic ischemia by measuring mitochondrial (m)Ca2+, NADH, and reactive
      oxygen species (ROS) by online spectrophotofluorometry in intact hearts. METHODS:
      A fiberoptic cable was placed against the left ventricle of Langendorff-prepared
      guinea pig hearts to excite and record transmyocardial fluorescence at the
      appropriate wavelengths during 37 and 17 degrees C perfusion and during 30 min
      ischemia at 37 and 17 degrees C before 120 min reperfusion/rewarming. RESULTS:
      Cold perfusion caused significant reversible increases in m[Ca2+], NADH, and ROS.
      Hypothermia prevented a further increase in m[Ca2+], excess ROS formation and
      NADH oxidation/reduction imbalance during ischemia, led to a rapid return to
      preischemic values on warm reperfusion, and preserved cardiac function and tissue
      viability on reperfusion. CONCLUSIONS: Hypothermic perfusion at 17 degrees C
      caused moderate and reversible changes in mitochondrial function. However,
      hypothermia protects during ischemia, as shown by preservation of mitochondrial
      NADH energy balance and prevention of deleterious increases in m[Ca2+] and ROS
      formation. The close temporal relations of these factors during cooling and
      during ischemia suggest a causal link between mCa2+, mitochondrial energy
      balance, and ROS production.

PMID- 14962489
TI  - Remote preconditioning by infrarenal aortic occlusion is operative via delta1
      opioid receptors and free radicals in vivo in the rat heart.
AB  - BACKGROUND: Ischemic preconditioning (PC) is a powerful mechanism in reducing
      infarct size of the heart. Protection can be performed either by an ischemic
      stimulus of the heart itself or by ischemia of an organ distant to the heart
      (remote PC). We have previously shown that remote PC by infrarenal occlusion of
      the aorta [IOA] in the rat is as powerful as classical ischemic PC. This
      protection may be transmitted by humoral factors, and protein kinase C is a
      mediator in the signal transduction mechanism. Focus of the present study was to
      address the question whether remote preconditioning is dependent on the
      activation of the delta1-opioid receptor and/or free radicals, the infarct size
      was determined after either inhibition of the delta1-opioid receptor or
      scavenging free radicals. METHODS AND RESULTS: IOA was performed in rats by
      occlusion of the infrarenal aorta for 15 min followed by a 10-min reperfusion
      period. Infarction of the heart was induced by 30 min regional ischemia followed
      by 30 min of reperfusion. The area of infarct was determined by propidium iodide
      and the risk zone was demarcated by zinc cadmium sulfide fluorescent particles.
      Control hearts (30 min regional ischemia of the heart followed by 30 min of
      reperfusion; no IOA) had an infarct size of 54 +/- 3%, whereas classical
      preconditioning by three ischemia/reperfusion [I/R] cycles, 5 min each, reduced
      it to 12 +/- 1% of the risk zone (p<0.05). Fifteen minutes IOA with 10 min of
      reperfusion was highly protective and reduced the infarct size to 20 +/- 5%
      (p<0.05 vs. control). Inhibition of the delta1-opioid receptors by 7
      benzylidenenaltrexone [BNTX] blocked the protection obtained by PC and IOA (41 +/
      4% and 44 +/- 2%, respectively; p<0.05 vs. the group without BNTX). BNTX in
      control hearts had no influence on infarct size (52 +/- 2%). Inhibition of
      endogenously released radicals by N-2-mercaptopropionyl glycine [MPG] blocked the
      infarct size reduction of IOA (46 +/- 3%; p<0.05 vs. IOA), but had no influence
      on the protection in classically preconditioned hearts protected by three cycles
      I/R (13 +/- 4%). Only if the number of the preconditioning stimuli was reduced to
      one was MPG able to overcome the protection (43 +/- 4%, p<0.05 vs. PC with one
      I/R cycle (21 +/- 4%)). CONCLUSION: Remote preconditioning using IOA protects the
      rat heart from infarction. Classical and remote PC share both the delta1-opioid
      receptor and free radicals as common elements in their signal transduction
      pathways. MPG can block protection from IOA and from one, but not from three,
      classical preconditioning cycles. This indicates that the protection by remote
      preconditioning is comparable to classical PC with one I/R cycle.

PMID- 14962490
TI  - Delayed preconditioning of the human myocardium: signal transduction and clinical
      implications.
AB  - OBJECTIVE: Ischemic preconditioning confers cardioprotection in early and delayed
      phases. We investigated the delayed window of pharmacological and ischemic
      preconditioning in human myocardium, and the involvement of mitoKATP, PKC and
      p38MAPK. METHODS: These studies were carried out using human right atrial tissue
      in a cell necrosis model. The tissue was obtained from patients undergoing
      coronary artery surgery. RESULTS: The second window triggered by ischemia,
      phenylephrine or adenosine resulted in similar cardioprotection between 24 and 72
      h following the intervention. Atrial tissue taken from patients with a single
      episode of angina between 24 and 72 h prior to surgery were already protected and
      preconditioning with ischemia, phenylephrine or adenosine did not add to the
      protection. The trigger of preconditioning with mitoKATP channel opener
      diazoxide, PKC activator PMA and p38MAPK activator anisomycin produced similar
      delayed protection to that of ischemia or phenylephrine. Cardioprotection was
      lost when mitoKATP channels were blocked by 5HD, PKC by chelerythrine and p38MAPK
      by SB203580 24 h after the trigger of preconditioning. CONCLUSIONS: Ischemic and
      pharmacological preconditioning induce similar delayed cardioprotection of the
      human heart. This second window of protection that is seen between 24 and 72 h
      occurs in vitro and in vivo and requires opening of mitoKATP channels and
      activation of PKC and p38MAPK.

PMID- 14962491
TI  - Ischemic preconditioning activates AMPK in a PKC-dependent manner and induces
      GLUT4 up-regulation in the late phase of cardioprotection.
AB  - OBJECTIVE: The aim of this study was to determine the role of AMP-activated
      protein kinase (AMPK) and its link to protein kinase C (PKC) in the late phase of
      cardioprotection afforded by ischemic preconditioning (PC) against myocardial
      stunning. METHODS AND RESULTS: Rabbits were instrumented with a balloon occluder
      around a coronary artery and with a Doppler sensor to monitor the thickening
      fraction (TF). Conscious rabbits underwent five cycles of 5-min ischemia/5-min
      reperfusion (I/R) on 2 consecutive days (days 1 and 2). Reduction of TF after I/R
      was significantly less and recovery of TF was faster on day 2, indicating a late
      PC effect. PC provoked translocation of PKC- from the cytosol to the membrane and
      significantly increased AMPK activity by 100% immediately after PC. The mRNA
      level of GLUT4, a glucose transporter, was elevated by 150% at 3 h after PC, and
      the total protein level of GLUT4 was increased by 107% at 24 h after PC. The
      level of sarcolemmal GLUT4 protein after I/R on day 2 was 41% higher than its
      level after I/R on day 1. AMPK activation and up-regulation of GLUT4 by PC were
      abrogated by pre-treatment with PKC inhibitors. CONCLUSION: PC activated AMPK and
      up-regulated GLUT4 expression in a PKC-dependent manner. This GLUT4 up-regulation
      at 24 h after PC may contribute to attenuation of myocardial stunning.

PMID- 14962492
TI  - Pharmacological therapy can increase capillary density in post-infarction
      remodeled rat hearts.
AB  - OBJECTIVE: Postinfarction hypertrophied hearts have been shown to display a lower
      capillary density and reduced mechanical efficiency amplified by tachycardia. We
      investigated whether pharmacological reduction of postinfarction tachycardia
      would induce capillary growth by treating myocardial infarcted (MI) rats with
      aspirin, methylprednisolone, moxonidine or captopril, during the first 3 weeks
      after infarction. METHODS AND RESULTS: Effects on in vivo heart rate were
      measured in conscious unrestrained rats, while in vitro heart rate effects were
      evaluated in isolated perfused hearts. Compared to sham-rats, MI-rats manifested
      a significant in vivo as well as in vitro tachycardia (increase 9% and 20% vs.
      sham, respectively). Whereas aspirin, methylprednisolone and moxonidine
      significantly reduced postinfarction in vivo tachycardia, captopril rather
      increased in vivo heart rate. In vitro tachycardia of MI-hearts was reduced to
      sham-values with aspirin and methylprednisolone (P<0.05), but not with moxonidine
      and captopril. Capillary density defined as the number of Lectin stained
      capillaries per tissue area, which significantly decreased in MI-hearts (decrease
      42% vs. sham), was restored by all treatments (P<0.05). Concentric left
      ventricular hypertrophy after MI, defined as increased cross-sectional area of
      transversally cut Gomori stained myocytes, was indicated by almost double myocyte
      size (P<0.05), while capillary to myocyte ratio remained unchanged.
      Methylprednisolone, moxonidine and captopril, but not aspirin, prevented
      hypertrophy (P<0.05). However, treatment with aspirin and methylprednisolone, but
      not moxonidine and captopril, increased capillary to myocyte ratio (P<0.05) up to
      twice the values of non-treated MI hearts, indicating newly formed capillaries.
      CONCLUSIONS: The above findings confirm that post-MI pharmacological treatment
      can increase capillary density in the remodeled left ventricle. Whereas
      prevention of left ventricular hypertrophy normalizes capillary density without
      actually affecting capillary number, increased capillary to myocyte ratio (at
      preserved hypertrophic response) indicates actual capillary growth.

PMID- 14962493
TI  - The cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J2
      ameliorates ischemic acute renal failure.
AB  - OBJECTIVE: Here we investigate the effects of the endogenous prostaglandin D2
      metabolite 15-deoxy-Delta(12,14)-prostaglandin J2, on the renal dysfunction and
      injury caused by ischemia/reperfusion of the kidney. METHODS: Male Wistar rats,
      subjected to bilateral renal ischemia for 45 min followed by reperfusion for up
      to 48 h, were administered 15-deoxy-Delta(12,14)-prostaglandin J2 (1 mg/kg,
      intravenously) 5 min prior to and again after 3 or 12 h reperfusion. RESULTS: 15
      deoxy-Delta(12,14)-prostaglandin J2 significantly reduced (i) renal and tubular
      dysfunction (serum urea and creatinine levels, creatinine clearance, fractional
      excretion of Na+ (FENA)), (ii) tubular and reperfusion-injury (urinary N-acetyl
      beta-D-glucosaminidase, aspartate aminotransferase (ASP) and gamma
      glutamyltransferase (gamma-GT)) and (iii) histological evidence of renal injury.
      15-deoxy-Delta(12,14)-prostaglandin J2 also improved renal function (plasma
      creatinine levels) and reduced the histological signs of renal injury (after 48 h
      reperfusion). Administration of 15-deoxy-Delta(12,14)-prostaglandin J2 markedly
      reduced the expression of inducible nitric oxide synthase (iNOS) and
      intercellular adhesion molecule-1 during reperfusion (determined using
      immunohistochemistry). Immunohistochemical analysis of p65 translocation and
      Western blot analysis of IkappaB-alpha degradation revealed that 15-deoxy
      Delta(12,14)-prostaglandin J2 inhibited the activation of nuclear factor (NF)
      kappaB in renal cells. Subsequently, 15d-PGJ2 was able to significantly reduce
      nitric oxide production during renal ischemia/reperfusion and by primary cultures
      of rat proximal tubular (PT) cells incubated with interferon-gamma and bacterial
      lipopolysaccharide (LPS) in combination. CONCLUSIONS: We demonstrate here, for
      the first time, that 15-deoxy-Delta(12,14)-prostaglandin J2 significantly reduces
      renal ischemia/reperfusion-injury via reduction of pro-inflammatory gene
      expression during reperfusion subsequent to the inhibition of the activation of
      NF-kappaB.

PMID- 14962494
TI  - Calcitonin gene-related peptide indirectly inhibits IL-7 responses in pre-B cells
      by induction of IL-6 and TNF-alpha in bone marrow.
AB  - Calcitonin gene-related peptide (CGRP) has inflammatory and immunoregulatory
      properties. CGRP directly inhibits IL-7 induced proliferation in developing B
      cells and also induces soluble factors that inhibit IL-7 responses. We identified
      2 cytokines, IL-6 and TNF-alpha, induced by CGRP, that inhibit IL-7 pre-B cell
      responses. CGRP induction of IL-6 and TNF-alpha mRNA in long-term bone marrow
      cultures is transient and IL-6 or TNF-alpha inhibit IL-7 induced colony formation
      by 60%. When added with CGRP, colony formation is completely inhibited. TNF-alpha
      directly inhibits IL-7 responses in B220(+)/IgM(-) cells whereas IL-6 inhibits
      only colony formation with whole bone marrow. This suggests that the effect of IL
      6 is mediated by other cells in the bone marrow. These results suggest that the
      indirect effect of CGRP on IL-7 depends in part on induction of IL-6 and TNF
      alpha.

PMID- 14962495
TI  - Caspase involvement in RIP-associated CD95-induced T cell apoptosis.
AB  - CD95-induced apoptosis is an important regulatory mechanism in T cells and this
      complex signalling pathway is now thought to include the protein kinase RIP.
      Although, RIP is best known for its role in TNF signalling and NF-kappaB
      activation, it contains a death domain and it is capable of causing apoptosis
      upon cleavage. In the present study, the role of RIP in CD95-induced apoptosis
      and its inter-relationship with the caspase cascade was investigated. Studies
      were performed on both a RIP-/- T cell line and peripheral T lymphocytes, where
      RIP was degraded through the addition of geldanamycin. Apoptosis was induced by
      membrane CD95-L, thought to be the most physiological relevant form of CD95-L.
      Results showed that RIP-/- cells had a decreased susceptibility to death, thus
      confirming a role for RIP in CD95-induced apoptosis. Furthermore, it was
      confirmed that RIP is cleaved upon CD95-L stimulation, a process that can be
      inhibited by Z-VAD. However, only partial inhibition in peripheral T lymphocytes
      by Z-VAD was observed, suggesting a potential caspase-independent processing of
      RIP. Studies performed on the activity of effector caspase 3 and on the initiator
      caspases 2, 8, and 9 revealed that, in the absence of RIP, the activity of these
      caspases decreases, indicating that RIP-associated apoptosis is caspase
      dependent. Hence, these studies support a caspase-related role for RIP in CD95
      induced T apoptosis.

PMID- 14962496
TI  - Immunomodulatory action of spermine and spermidine on NR8383 macrophage line in
      various culture conditions.
AB  - We examined the effect of spermine (SPM) and spermidine (SPD) on tumor necrosis
      factor (TNF)alpha and monocyte chemoattractant protein-1 (MCP-1) secretion from
      macrophages in various culture conditions, including several protocols of
      polyamines addition and media supplemented with 0, 1 or 15% fetal bovine serum.
      TNFalpha secretion was inhibited by SPM or SPD added 18h before stimulation in a
      concentration-dependent manner. Their effect was directly related to the presence
      of FBS. When SPM or SPD was added simultaneously to the stimulus, the TNFalpha
      secretion inhibition was higher than that obtained after pre-treatment. In this
      case, the effect was inversely proportional to the presence of FBS. The addition
      of polyamines also inhibited the secretion of MCP-1 in NR8383 cells. We conclude
      that SPM and SPD inhibited the secretion of inflammatory cytokines TNFalpha and
      MCP-1 in different ways, depending on culture conditions. In any case, SPM was
      more effective than SPD.

PMID- 14962497
TI  - The avian chB6 alloantigen induces apoptosis in DT40 B cells.
AB  - In avian species, B-lymphocytes develop in the bursa of Fabricius. Cells
      developing in the bursa are subject to signals regulating their survival, with
      the majority of cells dying by apoptosis within the bursa. However, the molecules
      delivering the signals influencing this life and death decision remain enigmatic.
      We have previously shown that antibodies against the chB6 alloantigen present on
      avian B-lymphocytes can induce a rapid form of cell death. Here we extend this
      finding by showing that anti-chB6 antibodies induce true apoptosis in DT40 cells
      without visible membrane damage. This apoptosis results in DNA degradation and
      morphologic changes characteristic of apoptosis. Furthermore, this apoptosis is
      coincident with a loss of mitochondrial membrane potential and is inhibited by
      either overexpression of bcl-x(L) or the presence of inhibitors of caspase 8, 9,
      or 3 activity. Collectively these data argue that chB6 may function as a novel
      death receptor on avian B-lymphocytes and support the use of DT40 as an amenable
      model to study the signaling involved in chB6-induced apoptosis.

PMID- 14962498
TI  - Cytokine production in association with phagocytosis of apoptotic cells by
      immature dendritic cells.
AB  - Immature dendritic cells (iDCs) can ingest apoptotic cells, which do not lead to
      maturation of the iDCs. In this paper we examine the phagocytosis of apoptotic
      cells by iDCs in the absence of stimuli for the maturation of iDCs and the
      subsequent cytokine production. Phagocytosis was observed by confocal microscopy,
      and it increased as apoptosis proceeded. The coculturing of iDCs with apoptotic
      cells did not induce the maturation of iDCs even after the subsequent LPS
      treatment, as assessed as to the expression of MHC class II, CD80, CD86, and
      CD40. Moreover, IL-6 and IL-12p40 among the cytokines examined were specifically
      up-regulated by the coculturing at the mRNA and protein levels. The coculturing
      decreased the expression of MHC class II on iDCs and allogenic T cell
      proliferation induced by iDCs. Although anti-IL-6 antibodies only partially
      reversed the effect of coculturing with apoptotic cells, exogenous IL-6 decreased
      significantly the expression of MHC class II on iDCs and allogenic T cell
      proliferation induced by iDCs, raising the possibility that IL-6 may be partly
      involved in maintaining the immature status of iDCs in an autocrine manner.

PMID- 14962499
TI  - Skin immune responses to peptide and protein antigen are TLR4 independent.
AB  - Little is known about the innate immune mechanisms regulating adaptive immune
      responses elicited through the skin. Tissue injury is postulated to liberate Toll
      like receptor 4 (TLR4) ligands. In this study, we determined whether TLR4
      signaling modulates the response to epidermal injury induced by tape stripping
      (TS) and whether it alters humoral and cellular immune responses generated
      through epicutaneous immunization with peptide+cholera toxin (CT). The combined
      use of cholera toxin and TS with antigen promoted optimal antigen-specific CD4(+)
      and CD8(+) T cell proliferation in Balb/c and C57BL/6 mice, respectively. TLR4
      mutant mice had similar T cell responses to wild type mice. Further, OVA-protein
      specific IgG, IgG(1), IgG(2a), and IgE titers were similar in wild type and TLR4
      mutant mice. Thus, TLR4 signaling was not required for the generation of
      epicutaneous T cell or antibody mediated immune responses and did not alter the
      quality of the immune responses elicited.

PMID- 14962500
TI  - Inflammatory effects of coarse and fine particulate matter in relation to
      chemical and biological constituents.
AB  - There is conflicting evidence in the literature as to the predominant mechanism
      and also the compositional element(s) that drives the pulmonary inflammatory
      response of ambient particulate matter (PM). We have investigated the
      inflammogenic potential of coarse (2.5-10 microm) and fine (<2.5 microm) PM from
      both a rural and an industrial location in Germany, using bronchoalveolar lavage
      (BAL) of rat lungs 18 h post intratracheal instillation with PM. Irrespective of
      the sampling location, the coarse fraction of PM(10) but not its fine counterpart
      caused neutrophilic inflammation in rat lungs, in the absence of any severe
      pulmonary toxicity as indicated by the lack of an increase in lavage protein and
      lactate dehydrogenase levels. The rural sample of coarse PM also caused a
      significant increase in the tumor necrosis factor alpha (TNFalpha) content as
      well as glutathione depletion in the BAL fluid. The contrasting inflammatory
      responses of the different samples could not be explained by differences in the
      concentrations of soluble Fe, Cu, V, Ni, Cr, or Al or by the.OH generating
      capacities of the PM suspensions. However, the effects of the different PM
      samples were clearly associated with their endotoxin content, as well as their
      ability to induce interleukin (IL)-8 and TNFalpha from whole blood in vitro. In
      conclusion, on an equal mass basis, coarse but not fine PM samples from our
      sampling campaign induced an inflammatory reaction in the lung in the absence of
      gross cellular lung damage, following intratracheal instillation. Our data also
      indicate, in accordance with previous independent in vitro observations, that
      endotoxin or related contaminants may play a role in these in vivo effects.

PMID- 14962501
TI  - Activation of plasma membrane reduced glutathione transport in death receptor
      apoptosis of HepG2 cells.
AB  - Cells undergoing apoptosis release reduced glutathione (GSH) into the
      extracellular space; however, the physiological significance and the mechanism
      behind the GSH export remain unclear. The present study demonstrates that GSH is
      released by HepG2 cells undergoing Fas, tumor necrosis factor alpha (TNFalpha),
      or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-stimulated
      cell death. GSH release was observed at times when extracellular lactate
      dehydrogenase (LDH) activity and propidium iodide (PI) incorporation were low,
      suggesting that the GSH release does not occur because of nonspecific cell
      damage, but is occurring through a specific transport system. Caspase 3-like
      proteases were activated before GSH was released, indicating that protease may be
      involved in signaling GSH release. To investigate the mechanism of GSH release,
      studies were performed in the presence of GSH transport inhibitors, as well as 25
      mM GSH in the media. Two organic anion transporter inhibitors, probenecid and
      dibromosulfophthalein (DBSP), were effective in inhibiting Fas-stimulated GSH
      release. The addition of 25 mM GSH to the extracellular media also prevented the
      loss of intracellular GSH and delayed cell death. These findings suggest that an
      organic anion transporter is involved in GSH release during apoptosis, and that
      maintenance of intracellular GSH levels during apoptosis provides protection for
      the cell.

PMID- 14962502
TI  - Exposure parameters necessary for delayed puberty and mammary gland development
      in Long-Evans rats exposed in utero to atrazine.
AB  - Our studies suggested that prenatal exposure to the herbicide atrazine (ATR)
      could delay vaginal opening (VO) and mammary development in the offspring of Long
      Evans (LE) rats. To evaluate ATR exposure parameters required for pubertal
      delays, including mammary gland development, we used cross-fostering to determine
      if effects were strictly dam-mediated (via milk) or a direct effect
      (transplacental) on the pups. Timed-pregnant LE rats (N = 20/treatment group)
      were gavaged on gestational days (GD) 15-19 with 100 mg ATR/kg body weight (BW)
      or vehicle (controls, C). On PND1, half of all litters were cross-fostered,
      creating four treatment groups: C-C, ATR-C, C-ATR, and ATR-ATR (dam-milk source,
      respectively). A significant delay in VO and increase in VO BW was seen only in
      the litters receiving milk from ATR-exposed dams. However, mammary glands of
      female offspring (two per dam) in all groups exposed to ATR (ATR-C, C-ATR, and
      ATR-ATR) displayed significant delays in epithelial development. These changes
      were detected as early as PND4 and stunted development was evident through PND40.
      Further, at all developmental stages examined, offspring in the ATR-ATR group
      exhibited the least developed glands. These delays in pubertal endpoints do not
      appear to be related to body weight or endocrine hormone concentrations. Our data
      suggest that the delay in VO of ATR-exposed offspring (C-ATR lactationally, ATR
      ATR lactationally and in utero) is mediated via the dam [milk], whereas brief
      direct exposure to ATR in utero can cause delays in mammary gland development.
      Our data suggest that milk-derived factors (growth factors or hormones), in
      addition to transplacental exposure during mammary bud outgrowth, may be involved
      in ATR mode of action on delayed mammary gland development.

PMID- 14962503
TI  - Pulmonary and systemic effects of short-term inhalation exposure to ultrafine
      carbon black particles.
AB  - While environmental particles are associated with mortality and morbidity related
      to pulmonary and cardiovascular (CV) disease, the mechanisms involved in CV
      health effects are not known. Changes in systemic clotting factors have been
      associated with pulmonary inflammation. We hypothesized that inhaled ultrafine
      particles result in an inflammatory response which may stimulate systemic
      clotting factor release. Adult male Wistar rats were exposed to either fine or
      ultrafine carbon black (CB) for 7 h. The attained total suspended particle
      concentrations were 1.66 mg/m(3) for ultrafine CB and 1.40 mg/m(3) for fine CB.
      Particle concentration of ultrafine particles was more than 10 times greater than
      that of fine particles and the count median aerodynamic diameter averaged 114 nm
      for the ultrafine and 268 nm for the fine carbon particles. Data were collected
      immediately, 16 and 48 h following exposure. Only ultrafine CB caused an increase
      in total bronchoalveolar lavage (BAL) leukocytes, whereas both fine (2-fold) and
      ultrafine (4-fold) carbon particles caused an increase in BAL neutrophils at 16 h
      postexposure. Exposure to the ultrafine, but not fine, carbon was also associated
      with significant increases in the total numbers of blood leukocytes. Plasma
      fibrinogen, factor VII and von Willebrand factor (vWF) were unaffected by
      particle treatments as was plasma Trolox equivalent antioxidant status (TEAC).
      Macrophage inflammatory protein-2 mRNA was significantly increased in BAL cells
      48 h following exposure to ultrafine CB. The data show that there is a small but
      consistent significant proinflammatory effect of this exposure to ultrafine
      particles that is greater than the effect of the same exposure to fine CB.

PMID- 14962504
TI  - Role of inducible nitric oxide synthase-derived nitric oxide in
      lipopolysaccharide plus interferon-gamma-induced pulmonary inflammation.
AB  - Exposure of mice to lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)
      increases nitric oxide (NO) production, which is proposed to play a role in the
      resulting pulmonary damage and inflammation. To determine the role of inducible
      nitric oxide synthase (iNOS)-induced NO in this lung reaction, the responses of
      inducible nitric oxide synthase knockout (iNOS KO) versus C57BL/6J wild-type (WT)
      mice to aspirated LPS + IFN-gamma were compared. Male mice (8-10 weeks) were
      exposed to LPS (1.2 mg/kg) + IFN-gamma (5000 U/mouse) or saline. At 24 or 72 h
      postexposure, lungs were lavaged with saline and the acellular fluid from the
      first bronchoalveolar lavage (BAL) was analyzed for total antioxidant capacity
      (TAC), lactate dehydrogenase (LDH) activity, albumin, tumor necrosis factor-alpha
      (TNF-alpha), and macrophage inflammatory protein-2 (MIP-2). The cellular fraction
      of the total BAL was used to determine alveolar macrophage (AM) and
      polymorphonuclear leukocyte (PMN) counts, and AM zymosan-stimulated
      chemiluminescence (AM-CL). Pulmonary responses 24 h postexposure to LPS + IFN
      gamma were characterized by significantly decreased TAC, increased BAL AMs and
      PMNs, LDH, albumin, TNF-alpha, and MIP-2, and enhanced AM-CL to the same extent
      in both WT and iNOS KO mice. Responses 72 h postexposure were similar; however,
      significant differences were found between WT and iNOS KO mice. iNOS KO mice
      demonstrated a greater decline in total antioxidant capacity, greater BAL PMNs,
      LDH, albumin, TNF-alpha, and MIP-2, and an enhanced AM-CL compared to the WT.
      These data suggest that the role of iNOS-derived NO in the pulmonary response to
      LPS + IFN-gamma is anti-inflammatory, and this becomes evident over time.

PMID- 14962505
TI  - A profile of the in vitro antitumor activity of lissoclinolide.
AB  - Lissoclinolide is a small non-nitrogenous lactone isolated from the marine
      ascidian Lissoclinum patella. Previous studies of lissoclinolide (isolated from a
      fungus and an actinomycete) have identified varying activity against both Gram
      negative and Gram-positive bacteria. In this study, lissoclinolide was able to
      inhibit cell growth in various mammalian tumor lines at an average IC(50) of 395
      nM (determined by MTT conversion after 48-h treatment). Treatment of HCT 116
      human colon tumor cells with 2.4 microM lissoclinolide resulted in a strong
      arrest in the G(2)/M phase of the cell cycle after 24-h exposure. A daughter cell
      line lacking p53 showed an identical response while there was a slight increase
      in cytotoxicity towards a p21 null cell line. Although treatment with 2.4 microM
      lissoclinolide did not result in apoptosis after 48 h, this arrest was not
      reversible when drug wash out was attempted. The mechanism of action does not
      appear to involve tubulin, ubiquitin-specific isopeptidases, p53 or p21. COMPARE
      analysis in the NCI 60 cell line tumor panel revealed a moderate selectivity
      towards colon tumor cell lines.

PMID- 14962506
TI  - Mechanisms of gastroprotection by lansoprazole pretreatment against
      experimentally induced injury in rats: role of mucosal oxidative damage and
      sulfhydryl compounds.
AB  - This study investigated the mechanisms involved in the protective actions exerted
      by lansoprazole against experimental gastric injury. Following the intraluminal
      injection of ethanol-HCl, the histomorphometric analysis of rat gastric sections
      demonstrated a pattern of mucosal lesions associated with a significant increase
      in the mucosal contents of malondialdehyde and 8-iso-prostaglandin F(2alpha)
      (indices of lipid peroxidation), as well as a decrease in the levels of mucosal
      sulfhydryl compounds, assayed as reduced glutathione (GSH). Pretreatment with
      lansoprazole 90 micromol/kg, given intraduodenally as single dose or once daily
      by intragastric route for 8 days, significantly prevented ethanol-HCl-induced
      gastric damage. The concomitant changes in the mucosal levels of malondialdehyde,
      8-iso-prostaglandin F(2alpha) and GSH elicited by ethanol-HCl were also
      counteracted by lansoprazole. In separate experiments, performed on animals
      undergoing 2-h pylorus ligation, lansoprazole did not enhance the concentration
      of prostaglandin E(2), bicyclo-prostaglandin E(2), or nitric oxide (NO)
      metabolites into gastric juice. Western blot analysis revealed the expression of
      both type 1 and 2 cyclooxygenase (COX) isoforms in the gastric mucosa of pylorus
      ligated rats. These expression patterns were not significantly modified by single
      dose or repeated treatment with lansoprazole. Lansoprazole also exhibited direct
      antioxidant properties by reducing 8-iso-prostaglandin F(2alpha) generation in an
      in vitro system where human native low-density lipoproteins were subjected to
      oxidation upon exposure to CuSO(4). The present results suggest that the
      protective effects of lansoprazole can be ascribed to a reduction of gastric
      oxidative injury, resulting in an increased bioavailability of mucosal sulfhydryl
      compounds. It is also proposed that lansoprazole does not exert modulator effects
      on the gastric expression of COX isoforms as well as on the activity of NO
      pathways.

PMID- 14962507
TI  - Development of an in vitro blood-brain barrier model-cytotoxicity of mercury and
      aluminum.
AB  - In this study, in vitro blood-brain barrier (BBB) models composed of two
      different cell types were compared. The aim of our study was to find an
      alternative human cell line that could be used in BBB models. Inorganic and
      organic mercury and aluminum were studied as model chemicals in the testing of
      the system. BBB models were composed of endothelial RBE4 cell line or retinal
      pigment epithelial (RPE) cell line ARPE-19 and neuronal SH-SY5Y cells as target
      cells. Glial U-373 MG cells were included in part of the tests to induce the
      formation of a tighter barrier. Millicell CM filter inserts were coated with rat
      tail collagen, and RBE4 or ARPE-19 cells were placed on the filters at the
      density of 3.5-4 x 10(5) cells/filter. During culture, the state of confluency
      was microscopically observed and confirmed by the measurement of electrical
      resistance caused by the developing cell layer. The target cells, SH-SY5Y
      neuroblastoma cells, were plated on the bottom of cell culture wells at the
      density of 100000 cells/cm(2). In part of the studies, glial U-373 MG cells were
      placed on the under side of the membrane filter. When confluent filters with ARPE
      19 or RBE4 cells were placed on top of the SH-SY5Y cells, different
      concentrations of mercuric chloride, methyl mercury chloride, and aluminum
      chloride were added into the filter cups along with a fluorescent tracer.
      Exposure time was 24 h, after which the cytotoxicity in the SH-SY5Y cell layer,
      as well as in the ARPE-19 or RBE4 cell layer, was evaluated by the luminescent
      measurement of total ATP. The leakage of the fluorescent tracer was also
      monitored. The results showed that both barrier cell types were induced by glial
      cells. Inorganic and organic mercury caused a leakage of the dye and cytotoxicity
      in SH-SY5Y cells. Especially, methyl mercury chloride could exert an effect on
      target cells before any profound cytotoxicity in barrier cells could be seen.
      Aluminum did not cause any leakage in the barrier cell layer, and even the
      highest concentration (1 mM) of aluminum did not cause any cytotoxicity in the SH
      SY5Y cells. In conclusion, BBB models composed of RBE4 and ARPE-19 cells were
      able to distinguish between different toxicities, and ARPE-19 cells are thus
      promising candidates for studies of drug penetration through the blood-brain
      barrier.

PMID- 14962508
TI  - A comparative study on the effects of 2,3,7,8,-tetrachlorodibenzo-p-dioxin
      polychlorinated biphenyl126 and estrogen in human bronchial epithelial cells.
AB  - Epidemiological studies on 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) exposure
      indicated high incidences of pulmonary dysfunctions and lung cancer. Animal
      studies also demonstrated lung cancer development in female, but not in male,
      rats exposed to TCDD. Such effects, however, have not been reported in
      polychlorinated biphenyls (PCB) exposure. In our present study, we have
      investigated the effects of TCDD and PCB126, with or without cotreatment with 17
      beta-estradiol (E2), on a human bronchial epithelial cell line BEAS-2B. We found
      that treatment with either TCDD or PCB126 alone reduced cell numbers as well as
      thymidine incorporation. Cell death, however, was only detected in PCB126-, but
      not TCDD-, treated cultures. The TCDD-induced cell reduction, therefore, could
      not be contributed to cell death. Meanwhile, because TCDD- and PCB126-enhanced
      CYP1A1 and CYP1B1 expressions were significantly reduced by the AhR antagonist
      and CYP1 inhibitor alpha-naphthoflavone (ANF), this indicated that the effects of
      TCDD and PCB126 were AhR and cytochrome p450 1 dependent. We also found that
      while E2 itself did not alter CYP1A1 and CYP1B1 expressions, cotreatment of E2
      with TCDD or PCB126 would significantly enhance TCDD-, but not PCB126-, induced
      toxicity. We further demonstrated that in the presence of E2, 1 nM TCDD increased
      the production of E2 metabolites, 2-methoxyestradiol (2-MeOE2) and 4
      methoxyestradiol (4-MeOE2). PCB126, however, only increased 2-MeOE2 formation
      without significant induction of 4-MeOE2. We believe that these metabolites,
      especially 4-MeOE2, interacted with TCDD to further suppress cell growth. Our
      data provided the first demonstration on the enhancement of TCDD-induced toxicity
      in human lung cells via interaction with estrogen.

PMID- 14962509
TI  - Polychlorinated biphenyl 126 stimulates basal and inducible aldosterone
      biosynthesis of human adrenocortical H295R cells.
AB  - To understand the effects of polychlorinated biphenyls (PCBs) on adrenal
      aldosterone biosynthesis, we have performed a systematical study to characterize
      the corresponding steroidogenic response of human adrenocortical cell line H295R
      to PCB126 exposure. We found that PCB126 at high concentrations stimulated basal
      and inducible aldosterone production. The aldosterone induction occurred
      concomitantly with activation of the CYP11B2 gene. Despite the fact that PCB126
      acted in synergy with both potassium and angiotensin II (Ang II) in activation of
      aldosterone synthesis, PCB126 only modestly increased CYP11B2 mRNA expression in
      the presence of Ang II contrary to the synergistic transcriptional induction
      elicited by PCB126 and potassium. This implicated that PCB126 had differential
      interactions with the potassium and Ang II signaling systems in the regulation of
      aldosterone biosynthesis. In addition, high concentrations of PCB126 elevated
      transcriptional expression of the type I Ang II receptor (AT(1)) and might thus
      sensitize the cellular Ang II responsiveness in both basal and inducible
      aldosterone biosynthesis. SF-1 was not involved in the PCB126-induced
      transcriptional regulation despite its importance in steroidogenic gene
      activation.

PMID- 14962510
TI  - A mechanistic study of cigarette smoke and cyclooxygenase-2 on proliferation of
      gastric cancer cells.
AB  - Cigarette smoke has been shown to cause gastric cancer. Overexpression of
      cyclooxygenase-2 (COX-2) is a common characteristic in gastric malignancy. The
      present study aimed to explore the correlation between cigarette smoke and COX-2
      in the promotion of tumorigenesis in human gastric cancer cells (AGS). We further
      studied the action of COX-2 on other proto-oncogenes on gastric tumor growth.
      Results showed that chloroform extract (CE) and ethanol extract (EE) from
      cigarette smoke dose-dependently stimulated gastric cancer cell proliferation,
      which was accompanied with an activation of ornithine decarboxylase (ODC)
      activity, COX-2, and c-myc expressions. Both antisense of c-myc and alpha
      difluoromethylornithine (DFMO, specific ODC inhibitor) inhibited cell
      proliferation without affecting COX-2 expression in response to cigarette smoke
      extracts (CSE). However, selective COX-2 inhibitor (SC-236) not only blocked the
      proliferative activity but also the ODC activity and c-myc protein expression by
      CSE in gastric cancer cells. Further, supplementation of exogenous prostaglandin
      (PG) E(2) reversed all the inhibitory actions of SC-236. Our results underline
      the importance of COX-2 in the cancer-promoting effect of CSE and its modulation
      on its downstream growth-related genes, such as c-myc and ODC in cancer cell
      proliferation. These results reveal that CSE-induced gastric carcinogenesis is
      via the COX-2/c-myc/ODC and PGE(2)-dependent pathway. Hence, selective COX-2
      inhibitor could be an effective therapeutic agent for gastric cancer in smokers.

PMID- 14962511
TI  - Pharmacokinetics and pharmacodynamic effects of amiodarone in plasma of ponies
      after single intravenous administration.
AB  - Atrial fibrillation is a well-known heart disease in horses. The common therapy
      consists of administration of quinidine. More potent antiarrhythmic drugs have
      become available for human therapy and the use of these as alternatives to
      quinidine for equine antiarrhythmic therapy is a matter of interest. Amiodarone
      (AMD) is used in human medicine for treatment of many arrhythmias, including
      atrial fibrillation. Its disposition in horses has not yet been investigated. The
      purpose of this study was to measure the effect of single intravenous doses of
      amiodarone (5 and 7 mg/kg) on the surface electrocardiogram (ECG) of healthy
      minishetland ponies during the first 2 days after drug administration and to
      calculate pharmacokinetic parameters with a physiologically based pharmacokinetic
      model (PBPK) using amiodarone and desethylamiodarone (DAMD) plasma levels that
      were determined by high-performance liquid chromatography (HPLC). As expected for
      a K(+)-channel-blocker, the main effect on the measured ECG could be seen on the
      ventricular complex, as the QT interval and the T wave showed statistically
      significant alterations. The doses investigated were well tolerated clinically.
      Results from the pharmacokinetic model were found to compare well with literature
      data of rats, dogs, and humans. It showed a rapid distribution in the tissue,
      beginning with the rapidly perfused tissue, like the heart, followed by slowly
      perfused tissues, and finally an accumulation in fat. The half-life for total
      elimination was calculated to be 16.3 days with 99% eliminated by 97 days. The
      model predicts that approximately 96% of amiodarone is eliminated as
      desethylamiodarone in urine, 2% eliminated as desethylamiodarone in bile, and 2%
      as other metabolites.

PMID- 14962512
TI  - Area under the curve as a dose metric for promotional responses following 2,3,7,8
      tetrachlorodibenzo-p-dioxin exposure.

PMID- 14962514
TI  - China: towards "xiaokang", but still living dangerously.

PMID- 14962515
TI  - Menopausal hormone therapy after breast cancer.

PMID- 14962516
TI  - vCJD tissue distribution and transmission by transfusion--a worst-case scenario
      coming true?

PMID- 14962517
TI  - Managing HIV lipoatrophy.

PMID- 14962518
TI  - Neuroprotective therapy for acute ischaemic stroke: down, but not out.

PMID- 14962519
TI  - Beryllium exposure and chronic beryllium disease.

PMID- 14962520
TI  - Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion.
AB  - BACKGROUND: Variant Creutzfeldt-Jakob disease (vCJD) is a novel human prion
      disease caused by infection with the agent of bovine spongiform encephalopathy
      (BSE). Epidemiological evidence does not suggest that sporadic CJD is transmitted
      from person to person via blood transfusion, but this evidence may not apply to
      vCJD. We aimed to identify whether vCJD is transmissible through blood
      transfusion. METHODS: The national CJD surveillance unit reported all cases of
      probable or definite vCJD to the UK blood services, which searched for donation
      records at blood centres and hospitals. Information on named recipients and
      donors was provided to the surveillance unit to establish if any matches existed
      between recipients or donors and the database of cases of vCJD. Recipients were
      also flagged at the UK Office of National Statistics to establish date and cause
      of death. FINDINGS: 48 individuals were identified as having received a labile
      blood component from a total of 15 donors who later became vCJD cases and
      appeared on the surveillance unit's register. One of these recipients was
      identified as developing symptoms of vCJD 6.5 years after receiving a transfusion
      of red cells donated by an individual 3.5 years before the donor developed
      symptoms of vCJD. INTERPRETATION: Our findings raise the possibility that this
      infection was transfusion transmitted. Infection in the recipient could have been
      due to past dietary exposure to the BSE agent. However, the age of the patient
      was well beyond that of most vCJD cases, and the chance of observing a case of
      vCJD in a recipient in the absence of transfusion transmitted infection is about
      1 in 15000 to 1 in 30000.

PMID- 14962521
TI  - Tissue distribution of bovine spongiform encephalopathy agent in primates after
      intravenous or oral infection.
AB  - BACKGROUND: The disease-associated form of prion protein (PrP(res)) has been
      noted in lymphoreticular tissues in patients with variant Creutzfeldt-Jakob
      disease (vCJD). Thus, the disease could be transmitted iatrogenically by surgery
      or use of blood products. We aimed to assess transmissibility of the bovine
      spongiform encephalopathy (BSE) agent to primates by the intravenous route and
      study its tissue distribution compared with infection by the oral route. METHODS:
      Cynomolgus macaques were infected either intravenously or orally with brain
      homogenates from first-passage animals with BSE. They were clinically monitored
      for occurrence of neurological signs and killed humanely at the terminal stage of
      the disease. Brain, lymphoreticular tissues, digestive tract, and peripheral
      nerves were obtained and analysed by sandwich ELISA and immunohistochemistry for
      quantitative and qualitative assessment of their PrP(res) content. FINDINGS:
      Incubation periods after intravenous transmission of BSE were much shorter than
      after oral infection. We noted that PrP(res) was present in lymphoreticular
      tissues such as spleen and tonsils and in the entire gut from the duodenum to the
      rectum. In the gut, PrP(res) was present in Peyer's patches and in the enteric
      nervous system and nerve fibres of intestinal mucosa. Furthermore, PrP(res) was
      found in locomotor peripheral nerves and the autonomic nervous system. Amount of
      PrP(res) ranged from 0.02% to more than 10% of that recorded in brain.
      Distribution of PrP(res) was similar in animals infected by the intravenous or
      oral route. INTERPRETATION: Our findings suggest that the possible risk of vCJD
      linked to endoscopic procedures might be currently underestimated. Human
      iatrogenic vCJD cases infected intravenously raise the same public-health
      concerns as primary cases and need the same precautionary measures with respect
      to blood and tissue donations and surgical procedures.

PMID- 14962523
TI  - No effect of rosiglitazone for treatment of HIV-1 lipoatrophy: randomised, double
      blind, placebo-controlled trial.
AB  - BACKGROUND: Lipodystrophy commonly complicates antiretroviral therapy of HIV-1
      infection. Thiazolidinediones such as rosiglitazone promote subcutaneous fat
      growth in type 2 diabetics and adults with congenital lipodystrophy, and can
      prevent HIV-1 protease inhibitor toxicity to adipocytes in vitro. We postulated
      that rosiglitazone would improve HIV lipoatrophy. METHODS: 108 HIV-1-infected
      lipoatrophic adults on antiretroviral therapy were randomised to rosiglitazone 4
      mg twice daily (n=53) or matching placebo (n=55) for 48 weeks. The study had 80%
      power to detect a 0.5 kg difference in changes in limb fat (using dual-energy X
      ray absorptiometry) between groups at week 48 by intention-to-treat analysis, and
      a 0.7 kg difference within each protease inhibitor stratum. FINDINGS: Limb fat
      increased by 0.14 kg in the rosiglitazone group and 0.18 kg in the placebo group
      (mean difference -0.04 kg [95%CI -0.29 to 0.21]; p=0.74 by t test), with three
      participants (one on rosiglitazone and two controls), lost to follow-up.
      Rosiglitazone had no significant benefit on any other measure of lipodystrophy,
      despite large relative increases in plasma adiponectin (4.2 mmol/L [102%];
      p<0.0001) and in three markers of insulin sensitivity (p=0.01 to 0.02). Six
      participants ceased study drug in each group, four participants (three on
      rosiglitazone and one control) for related adverse events. The main adverse
      effects, which seem to be almost unique to this population, were asymptomatic
      hypertriglyceridaemia (mean relative increase 0.9 mmol/L at week 48; p=0.04) and
      hypercholesterolaemia (1.5 mmol/L; p=0.001). INTERPRETATION: Rosiglitazone for 48
      weeks did not improve lipoatrophy in HIV-1-infected adults receiving
      antiretroviral therapy. Use of less toxic antiretroviral treatment is necessary
      to prevent lipoatrophy.

PMID- 14962524
TI  - Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial):
      randomised controlled trial.
AB  - BACKGROUND: Magnesium is neuroprotective in animal models of stroke, and findings
      of small clinical pilot trials suggest potential benefit in people. We aimed to
      test whether intravenous magnesium sulphate, given within 12 h of stroke onset,
      reduces death or disability at 90 days. METHODS: 2589 patients were randomised
      within 12h of acute stroke to receive 16 mmol MgSO4 intravenously over 15 min and
      then 65 mmol over 24 h, or matching placebo. Primary outcome was a global
      endpoint statistic expressed as the common odds ratio for death or disability at
      day 90. Secondary outcomes were mortality and death or disability, variously
      defined as Barthel score less than 95, Barthel score less than 60, and modified
      Rankin scale more than 1. Predefined subgroup analyses were for the primary
      endpoint in patients in whom treatment commenced within 6 h versus after 6 h,
      ischaemic versus non-ischaemic strokes, and cortical stroke syndromes versus non
      cortical strokes. Intention-to-treat and efficacy analyses were done. FINDINGS:
      The efficacy dataset included 2386 patients. Primary outcome was not improved by
      magnesium (odds ratio 0.95, 95% CI 0.80-1.13, p=0.59). Mortality was slightly
      higher in the magnesium-treated group than in the placebo group (hazard ratio
      1.18, 95% CI 0.97-1.42, p=0.098). Secondary outcomes did not show any treatment
      effect. Planned subgroup analyses showed benefit of magnesium in non-cortical
      strokes (p=0.011) whereas greater benefit had been expected in the cortical
      group. INTERPRETATION: Magnesium given within 12 h of acute stroke does not
      reduce the chances of death or disability significantly, although it may be of
      benefit in lacunar strokes.

PMID- 14962525
TI  - Epigenetic differences between Wilms' tumours in white and east-Asian children.
AB  - BACKGROUND: Variations in the international incidence of Wilms' tumour might be
      due to genetic factors. The maternal insulin-like growth factor 2 gene (IGF2) is
      imprinted in normal tissues, whereas in some Wilms' tumours and other tumour
      types the imprint is lost, leading to biallelic transcription of IGF2. We
      investigated whether the difference in incidence of Wilms' tumour between
      children of east-Asian descent and white children is due to variations in
      proportion of tumours with loss of IGF2 imprinting (IGF2 LOI). METHODS: We
      assessed IGF2 LOI by use of an ApaI polymorphism in IGF2 exon 9 or quantitative
      PCR measuring DNA methylation of the H19 and KvDMR1 alleles. The frequencies of
      perilobar nephrogenic rests associated with Wilms' tumour were assessed
      histologically in Japanese children and children of white and east-Asian descent.
      FINDINGS: IGF2 LOI was present in Wilms' tumours from predominantly white
      children from New Zealand (13 of 41 tumours) but absent in tumours from Japanese
      children (0 of 21 tumours; difference in proportions 0.32, 95% CI 0.07-0.52).
      Frequency of perilobar nephrogenic rests accompanying tumours from white American
      children (1192 of 5002, 24%) was significantly higher than in Japanese (one of
      56, 1%, difference in proportions 0.22, 95% CI 0.14-0.25) and east-Asian American
      children (seven of 92, 8%, 0.16, 0.09-0.21). INTERPRETATION: Wilms' tumours in
      the east-Asian population rarely arise from the IGF2 LOI mechanism frequently
      noted in white patients. Our findings that IGF2 LOI and perilobar nephrogenic
      rests associated with this mechanism arise at low frequency in Japanese and east
      Asian American children lend support to this conclusion. Variation in frequency
      of this epigenetic mechanism provides one explanation for the difference in
      incidence of Wilms' tumour between populations.

PMID- 14962526
TI  - Chest pain? Cause.

PMID- 14962527
TI  - HABITS (hormonal replacement therapy after breast cancer--is it safe?), a
      randomised comparison: trial stopped.
AB  - In the 1990s, two randomised clinical trials started in Scandinavia addressing
      whether hormone replacement therapy (HRT) is safe for women with previous breast
      cancer. We report the findings of the safety analysis in HABITS (hormonal
      replacement therapy after breast cancer--is it safe?), an open randomised
      clinical trial with allocation to either HRT or best treatment without hormones.
      The main endpoint was any new breast cancer event. All analyses were done
      according to intention-to-treat. Until September, 2003, 434 women were
      randomised; 345 had at least one follow-up report. After a median follow-up of
      2.1 years, 26 women in the HRT group and seven in the non-HRT group had a new
      breast-cancer event. All women with an event in the HRT group and two of those in
      the non-HRT group were exposed to HRT and most women had their event when on
      treatment. We decided that these findings indicated an unacceptable risk for
      women exposed to HRT in the HABITS trial, and the trial was terminated on Dec 17,
      2003.

PMID- 14962528
TI  - Hypertensive retinopathy.

PMID- 14962529
TI  - Otitis media.
AB  - Otitis media (OM) continues to be one of the most common childhood infections and
      is a major cause of morbidity in children. The pathogenesis of OM is
      multifactorial, involving the adaptive and native immune system, Eustachian-tube
      dysfunction, viral and bacterial load, and genetic and environmental factors.
      Initial observation seems to be suitable for many children with OM, but only if
      appropriate follow-up can be assured. In children younger than 2 years with a
      certain diagnosis of acute OM, antibiotics are advised. Surgical candidacy
      depends on associated symptoms, the child's developmental risk, and the
      anticipated chance of timely spontaneous resolution of the effusion. The
      recommended approach for surgery is to start with tympanostomy tube placement,
      eventually followed by adenoidectomy. The ideal intervention for OM, however,
      does not yet exist, and an urgent need remains to explore new and creative
      options based on modern insights into the pathophysiology of OM.

PMID- 14962530
TI  - Programmes and principles in treatment of multidrug-resistant tuberculosis.
AB  - Multidrug-resistant tuberculosis (MDR-TB) presents an increasing threat to global
      tuberculosis control. Many crucial management issues in MDR-TB treatment remain
      unanswered. We reviewed the existing scientific research on MDR-TB treatment,
      which consists entirely of retrospective cohort studies. Although direct
      comparisons of these studies are impossible, some insights can be gained: MDR-TB
      can and should be addressed therapeutically in resource-poor settings; starting
      of treatment early is crucial; aggressive treatment regimens and high-end dosing
      are recommended given the lower potency of second-line antituberculosis drugs;
      and strategies to improve treatment adherence, such as directly observed therapy,
      should be used. Opportunities to treat MDR-TB in developing countries are now
      possible through the Global Fund to Fight AIDS, TB, and Malaria, and the Green
      Light Committee for Access to Second-line Anti-tuberculosis Drugs. As treatment
      of MDR-TB becomes increasingly available in resource-poor areas, where it is
      needed most, further clinical and operational research is urgently needed to
      guide clinicians in the management of this disease.

PMID- 14962531
TI  - Transmission of HIV-1 infection in sub-Saharan Africa and effect of elimination
      of unsafe injections.
AB  - During the past year, a group has argued that unsafe injections are a major if
      not the main mode of HIV-1 transmission in sub-Saharan Africa. We review the main
      arguments used to question the epidemiological interpretations on the lead role
      of unsafe sex in HIV-1 transmission, and conclude there is no compelling evidence
      that unsafe injections are a predominant mode of HIV-1 transmission in sub
      Saharan Africa. Conversely, though there is a clear need to eliminate all unsafe
      injections, epidemiological evidence indicates that sexual transmission continues
      to be by far the major mode of spread of HIV-1 in the region. Increased efforts
      are needed to reduce sexual transmission of HIV-1.

PMID- 14962532
TI  - Geography of biomedical publications.

PMID- 14962534
TI  - Geography of biomedical publications.

PMID- 14962535
TI  - Peer-assisted learning in clinical examination.

PMID- 14962536
TI  - Medics, media, and mass confusion.

PMID- 14962537
TI  - Treatment of shoulder complaints.

PMID- 14962538
TI  - Medical publishers: a charity worth supporting?

PMID- 14962540
TI  - Treatment of shoulder complaints.

PMID- 14962541
TI  - Access to antiretrovirals: where South Africa, China, and Brazil meet.

PMID- 14962542
TI  - HAART in India.

PMID- 14962544
TI  - Chirwa's son.

PMID- 14962543
TI  - "Opt-out" testing for HIV in Africa: a caution.

PMID- 14962545
TI  - Setting standards.

PMID- 14962547
TI  - Risk factors.

PMID- 14962548
TI  - Pied piper.

PMID- 14962549
TI  - Time-dependent morphology and adhesion of osteoblastic cells on titanium model
      surfaces featuring scale-resolved topography.
AB  - The role of micrometer and submicrometer surface roughness on the interaction of
      cells with titanium model surfaces of well-defined topography was investigated
      using human bone-derived cells (MG63 cells). The early phase of interactions was
      studied using a kinetic morphological analysis of adhesion, spreading and
      proliferation of the cells. By SEM and double immunofluorescent labeling of
      vinculin and actin, it was found that the cells responded to nanoscale roughness
      by a higher cell thickness and a delayed apparition of the focal contacts. A
      singular behavior was observed on nanoporous oxide surfaces, where the cells were
      more spread and displayed longer and more numerous filopods. On electrochemically
      microstructured surfaces with hemispherical cavities, arranged in a hexagonal
      pattern, the MG63 cells were able to go inside, adhere and proliferate in
      cavities of 30 or 100 microm in diameter, whereas they did not recognize the 10
      microm diameter cavities. Cells adopted a 3D shape when attaching inside the 30
      microm diameter cavities. Condensation of actin cytoskeleton correlated with
      vinculin-positive focal contacts on cavity edges were observed on all
      microstructured surfaces. Nanotopography on surfaces with 30 microm diameter
      cavities had little effect on cell morphology compared to flat surfaces with same
      nanostructure, but cell proliferation exhibited a marked synergistic effect of
      microscale and nanoscale topography.

PMID- 14962550
TI  - The formation of poly(ester-urea) networks in the absence of isocyanate monomers.
AB  - The polymerization of N,N' carbonylbis (caprolactam) (CBC) and polyol in the
      presence of alcoholate as catalyst produced cross-linked poly(ester-urea)s via
      ring opening addition reaction. In contrast to conventional synthetic routes, the
      use of non-toxic CBC eliminates the need for toxic isocyanate-based monomers. The
      structure of the molecules resulting from model reactions was confirmed using FT
      IR and (1)H- and (13)C-NMR spectroscopy. Poly(ester-urea) networks exhibit rubber
      like mechanical properties and high-temperature stability. Cell adhesion and cell
      growth on the polymers evidenced the high biocompatibility of the material.
      Degradation of the poly(ester-urea)s was investigated at 70 degrees C in neutral
      and basic aqueous solution. The degradation depends on the swelling behavior of
      the samples. Mechanical properties, good biocompatibility, and degradation
      behavior of the CBC/polyol-based polymers make them interesting materials for
      biomedical applications.

PMID- 14962551
TI  - Self-assembled monolayers with different terminating groups as model substrates
      for cell adhesion studies.
AB  - Cell shapes induced by cell-substratum interactions are linked with
      proliferation, differentiation or apoptosis of cells. To clarify the relevance of
      specific surface characteristics, we applied self-assembled monolayers (SAM) of
      alkyl silanes exhibiting a variety of terminating functional groups. We first
      characterised the SAMs on glass or silicon wafers by measuring wettability, layer
      thickness and roughness. Water contact angle data revealed that methyl (CH(3)),
      bromine (Br), and vinyl (CH=CH(2)) groups lead to hydrophobic surfaces, while
      amine (NH(2)) and carboxyl (COOH) functions lead to moderately wettable surfaces,
      and polyethylene glycol (PEG) and hydroxyl (OH) groups created wettable
      substrata. The surfaces were found to be molecular smooth except for one type of
      NH(2) surface. The SDS-PAGE analysis of proteins adsorbed from bovine serum to
      the SAMs showed less protein adsorption to PEG and OH than to CH(3), NH(2) and
      COOH. Immunoblotting revealed that a key component of adsorbed proteins is
      vitronectin while fibronectin was not detectable. The interaction of human
      fibroblasts with CH(3), PEG and OH terminated SAMs was similarly weak while
      strong attachment, spreading, fibronectin matrix formation and growth were
      observed on COOH and NH(2). The strong interaction of fibroblasts with the latter
      SAMs was linked to an enhanced activity of integrins as observed after antibody
      tagging of living cells.

PMID- 14962552
TI  - Promotion of fibroblast activity by coating with hydrophobins in the beta-sheet
      end state.
AB  - Hydrophobins such as SC3 and SC4 of Schizophyllum commune self-assemble into an
      amphipathic film at hydrophilic/hydrophobic interfaces. These proteins can thus
      change the nature of surfaces, which makes them attractive candidates to improve
      physio- and physico-chemical properties of implant surfaces. At a hydrophobic
      solid, assembly of the hydrophobin is arrested in an intermediate state, called
      the alpha-helical state. The conversion to the stable beta-sheet end state can be
      induced by treating the solid at elevated temperatures in the presence of
      detergent. We here show that SC3 and SC4 in the alpha-helical state homogeneously
      cover Teflon sheets when coating was performed at 20 degrees C. However, when the
      protein was adsorbed at 80 degrees C aggregates were shown to bind tightly to the
      adsorbed hydrophobin film. The transition to the beta-sheet state created pores
      of about 50 nm in the SC3 and SC4 coatings when coating was performed at 20
      degrees C. Cell growth and morphology on SC4 coatings was better than on SC3. In
      case of both hydrophobins, fibroblast growth and morphology was not influenced by
      the coating temperature or the conformation of the protein. However, in contrast
      to the alpha-helical state, the beta-sheet state of both SC3 and SC4 hardly, if
      at all, affected mitochondrial activity.

PMID- 14962553
TI  - Adhesion and proliferation of human Schwann cells on adhesive coatings.
AB  - Attachment to and proliferation on the substrate are deemed important
      considerations when Schwann cells (SCs) are to be seeded in synthetic nerve
      grafts. Attachment is a prerequisite for the SCs to survive and fast
      proliferation will yield large numbers of SCs in a short time, which appears
      promising for stimulation of peripheral nerve regeneration. The aim of the
      present study was to compare the adhesion and proliferation of human Schwann
      cells (HSCs) on different substrates. The following were selected for their
      suitability as an internal coating of synthetic nerve grafts; the extracellular
      matrix proteins fibronectin, laminin and collagen type I and the poly
      electrolytes poly(d-lysine) (PDL) and poly(ethylene-imine) (PEI). On all
      coatings, attachment of HSCs was satisfactory and comparable, indicating that
      this factor is not a major consideration in choosing a suitable coating.
      Proliferation was best on fibronectin, laminin and PDL, and worst on collagen
      type I and PEI. Since nerve regeneration is enhanced by laminin and/or
      fibronectin, these are preferred as coatings for synthetic nerve grafts seeded
      with SCs.

PMID- 14962554
TI  - Oriented astroglial cell growth on micropatterned polystyrene substrates.
AB  - In an effort to develop a permissive environment for neural stem cell
      differentiation, directional growth of astrocytes has been achieved on polymer
      substrates in vitro. Manipulating a combination of physical and chemical cues,
      astrocyte adhesion and alignment in vitro were examined. To provide physical
      guidance, micropatterned polymer substrates of polystyrene (PS) were fabricated.
      Laminin was selectively adsorbed onto the grooves of the patterned surface. Rat
      type-1 astrocytes were seeded onto the micropatterned PS substrates, and the
      effects of substrate topography and the adsorption of laminin to the PS
      substrates on the behavior and morphology of the astrocytes were explored. The
      astrocytes were found to align parallel to the micropatterned grooves at initial
      seeding densities of approximately 7500, 13,000, and 20,000 cells/cm(2) due to
      the effects of the physical and chemical guidance mechanisms. Adsorbing laminin
      in the microgrooves of the micropatterned PS substrates improved cell adhesion
      and spreading of cytoskeletal filaments significantly. At these initial seeding
      densities, over 85% astrocyte alignment in the direction of the grooves was
      achieved on the micropatterned PS substrates with laminin adsorbed in the
      grooves. This combination of guidance cues has the potential to provide a
      permissive substrate for in vivo regeneration within the central nervous system.

PMID- 14962555
TI  - Fluid shear in viscous fibronectin gels allows aggregation of fibrous materials
      for CNS tissue engineering.
AB  - Fibronectin (Fn) materials prepared from human plasma have been used in various
      forms as substrates for tissue engineering. Such purposes require that the
      soluble protein aggregates into insoluble fibrous structures which encourage the
      attachment and migration of cells. The method of aggregation due to mechanical
      shear was investigated by applying fluid shear forces directly to a viscous
      solution of Fn. Structural analysis revealed that mechanical shear resulted in
      the formation of an orientated fibrous protein material that was less soluble
      than its non-sheared counterpart. The suitability of this shear aggregated Fn
      material for CNS repair purposes was assessed in vitro where it supported the
      growth of fibroblasts, S100 immunoreactive Schwann cells and GFAP immunoreactive
      astrocytes. Implantation of the shear aggregated Fn material into a rat model of
      spinal cord injury provided a permissive environment for axonal growth. This was
      extended using an impermeable coating to improve orientation and straightness of
      axonal growth.

PMID- 14962556
TI  - Chemical and biological integration of a mouldable bioactive ceramic material
      capable of forming apatite in vivo in teeth.
AB  - Chemically bonded ceramics have several advantages compared with conventional
      ceramics to be used as biomaterials. Especially the possibilities to harden the
      material at room temperature and to control the rheology are very beneficial.
      This paper investigates the interface formed in vivo between a calcium aluminate
      based dental filling material and teeth. Class 1 occlusal fillings were made in
      wisdom teeth and extracted after up to four weeks. Polished cross-sections of the
      teeth were studied with scanning electron microscopy (SEM), focused ion beam
      microscopy (FIB) and transmission electron microscopy (TEM). In order to analyse
      the distribution of elements at the interface elemental mapping was performed
      using STEM and EDX. The results showed that a tight bond forms between the
      filling material and tooth and no gap could be found even at high magnification.
      A 100-200 nm wide zone with an increase in oxygen was detected in the enamel next
      to the filling. The zone was denser than the rest of the enamel. Elemental
      mapping indicated an increase of silicon and a decrease of Ca at the interface.
      Dark field imaging and EDX mapping showed that the calcium aluminate system
      formed apatite in situ during hardening through precipitation.

PMID- 14962557
TI  - Stimulation of in vivo angiogenesis by cytokine-loaded hyaluronic acid hydrogel
      implants.
AB  - Crosslinked hyaluronic acid (HA) hydrogels were evaluated for their ability to
      elicit new microvessel growth in vivo when preloaded with one of two cytokines,
      vascular endothelial growth factor (VEGF) or basic fibroblast growth factor
      (bFGF). HA film samples were surgically implanted in the ear pinnas of mice, and
      the ears retrieved 7 or 14 days post implantation. Histologic analysis showed
      that all groups receiving an implant demonstrated significantly more microvessel
      density than control ears undergoing surgery but receiving no implant (p < 0.01).
      Moreover, aqueous administration of either growth factor produced substantially
      more vessel growth than an HA implant with no cytokine. However, the most
      striking result obtained was a dramatic synergistic interaction between HA and
      VEGF. Presentation of VEGF in crosslinked HA generated vessel density of NI = 6.7
      at day 14, where NI is a neovascularization index defined below, more than twice
      the effect of the sum of HA alone (NI = 1.8) plus VEGF alone (NI=1.3). This was
      twice the vessel density generated by co-addition of HA and bFGF (NI=3.4,
      p<0.001). New therapeutic approaches for numerous pathologies could be notably
      enhanced by the localized, synergistic angiogenic response produced by release of
      VEGF from crosslinked HA films.

PMID- 14962558
TI  - A novel use of centrifugal force for cell seeding into porous scaffolds.
AB  - A novel rotor was constructed to allow for the seeding of porous scaffolds via
      centrifugal force. Using cell seeding times of 10 min, this method placed
      significantly (roughly 3-fold) more cells into poly(glycolic acid) scaffolds than
      24 h of spinner flask seeding or static seeding. There were no significant
      differences in the mitochondrial activity per cell between the 3 seeding methods.
      Cell distribution was noted to be homogeneous throughout the scaffold thickness
      for the centrifugation method, as opposed to surface seeding for the spinner
      flask method. Centrifugation was especially efficient at low cell concentrations
      (1.33 x 10(5) cells/ml). This system is useful for the seeding of biomaterials
      having cylindrical or planar geometries, and may be used under conditions that
      require low cell numbers and/or short seeding time periods.

PMID- 14962559
TI  - In vitro characterization of natural and synthetic dermal matrices cultured with
      human dermal fibroblasts.
AB  - The ideal dermal matrix should be able to provide the right biological and
      physical environment to ensure homogenous cell and extracellular matrix (ECM)
      distribution, as well as the right size and morphology of the neo-tissue
      required. Four natural and synthetic 3D matrices were evaluated in vitro as
      dermal matrices, namely (1) equine collagen foam, TissuFleece, (2) acellular
      dermal replacement, Alloderm, (3) knitted poly(lactic-co-glycolic acid) (10:90)
      poly(-caprolactone) (PLGA-PCL) mesh, (4) chitosan scaffold. Human dermal
      fibroblasts were cultured on the specimens over 3 weeks. Cell morphology,
      distribution and viability were assessed by electron microscopy, histology and
      confocal laser microscopy. Metabolic activity and DNA synthesis were analysed via
      MTS metabolic assay and [(3)H]-thymidine uptake, while ECM protein expression was
      determined by immunohistochemistry. TissuFleece, Alloderm and PLGA-PCL mesh
      supported cell attachment, proliferation and neo-tissue formation. However,
      TissuFleece contracted to 10% of the original size while Alloderm supported cell
      proliferation predominantly on the surface of the material. PLGA-PCL mesh
      promoted more homogenous cell distribution and tissue formation. Chitosan
      scaffolds did not support cell attachment and proliferation. These results
      demonstrated that physical characteristics including porosity and mechanical
      stability to withstand cell contraction forces are important in determining the
      success of a dermal matrix material.

PMID- 14962560
TI  - Osteoblast response to PLGA tissue engineering scaffolds with PEO modified
      surface chemistries and demonstration of patterned cell response.
AB  - Because tissues are characterized by a well-defined three-dimensional arrangement
      of cells, tissue engineering scaffolds that facilitate the organization and
      differentiation of new tissue will have improved performance in comparison to
      scaffolds that only provide surfaces for cell attachment and growth. We
      hypothesize that instructions for cells can be incorporated into tissue
      engineering scaffolds by patterning the scaffold's architecture and surface
      chemistry. Our goals for the presented work were to collect data about cell
      response to three-dimensional, porous scaffolds with uniformly modified surfaces
      chemistries, and to demonstrate patterning of cell response by patterning surface
      chemistry. Our system was osteoblast response to poly(l-lactide-co-glycolide)
      scaffolds modified with poly(ethylene oxide) (PEO). Scaffolds were fabricated
      using the Three-Dimensional Printing (3DP) process which has control over
      scaffolds properties to a resolution of approximately 100 microm in all three
      dimensions. At higher PEO concentrations, adhesion, growth rates, and migration
      of rat osteoblasts were reduced; alkaline phosphate activity was increased, and
      cells were less spread and had microvilli. Patterned regions of low and high cell
      adhesion were demonstrated on scaffolds fabricated with 1 mm thick stripes of PEO
      and non-PEO regions.

PMID- 14962561
TI  - Influence of different collagen species on physico-chemical properties of
      crosslinked collagen matrices.
AB  - Collagen-based scaffolds are appealing products for the repair of cartilage
      defects using tissue engineering strategies. The present study investigated the
      species-related differences of collagen scaffolds with and without 1-ethyl-3-(3
      dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS)-crosslinking.
      Resistance against collagenase digestion, swelling ratio, amino acid sequence,
      shrinkage temperature, ultrastructural matrix morphology, crosslinking density
      and stress-strain characteristics were determined to evaluate the physico
      chemical properties of equine- and bovine-collagen-based scaffolds. Three-factor
      ANOVA analysis revealed a highly significant effect of collagen type (p=0.0001),
      crosslinking (p=0.0001) and time (p=0.0001) on degradation of the collagen
      samples by collagenase treatment. Crosslinked equine collagen samples showed a
      significantly reduced swelling ratio compared to bovine collagen samples (p<
      0.0001). The amino acid composition of equine collagen revealed a higher amount
      of hydroxylysine and lysine. Shrinkage temperatures of non-crosslinked samples
      showed a significant difference between equine (60 degrees C) and bovine collagen
      (57 degrees C). Three-factor ANOVA analysis revealed a highly significant effect
      of collagen type (p=0.0001), crosslinking (p=0.0001) and matrix condition
      (p=0.0001) on rupture strength measured by stress-strain analysis. The
      ultrastructure, the crosslinking density and the strain at rupture between
      collagen matrices of both species showed no significant differences. For tissue
      engineering purposes, the higher enzymatic stability, the higher form stability,
      as well as the lower risk of transmissible disease make the case for considering
      equine-based collagen. This study also indicates that results obtained for
      scaffolds based on a certain collagen species may not be transferable to
      scaffolds based on another, because of the differing physico-chemical properties.

PMID- 14962562
TI  - Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) nanoparticles for
      controlled delivery of anticancer drugs.
AB  - Methoxy poly(ethylene glycol)-poly(lactide) copolymer (MPEG-PLA) was synthesized
      and used to make nanoparticles by the nanoprecipitation method for clinical
      administration of antineoplastic drugs. Paclitaxel was used as a prototype drug
      due to its excellent efficacy and commercially great success. The size and size
      distribution, surface morphology, surface charge and surface chemistry of the
      paclitaxel-loaded nanoparticles were then investigated by laser light scattering,
      atomic force microscopy, zeta-potential analyzer and X-ray photoelectron
      spectroscopy (XPS). The drug encapsulation efficiency (EE) and in vitro release
      profile were measured by high-performance liquid chromatography. The effects of
      various formulation parameters were evaluated. The prepared nanoparticles were
      found of spherical shape with size less than 100 nm. Zeta potential measurement
      and XPS analysis demonstrated the presence of PEG layer on the particle surface.
      Viscosity of the organic phase was found to be one of the main process factors
      for the size determination. The EE was found to be greatly influenced by the drug
      loading. The drug release pattern was biphasic with a fast release rate followed
      by a slow one. The particle suspension exhibited good steric stability in vitro.
      Such a nanoparticle formulation of paclitaxel can be expected to have long
      circulating effects in circulation.

PMID- 14962563
TI  - Ethoxysilane-capped PEO-PPO-PEO triblocks: a new family of reverse thermo
      responsive polymers.
AB  - New reverse thermo-responsive polymers systems combining reverse thermal gelation
      behavior and a gradual increase in the mechanical properties, were created by
      crosslinking ethoxysilane-capped poly(ethylene oxide)-poly(propylene oxide)
      poly(ethylene oxide) triblocks in aqueous solutions at physiological conditions.
      Pluronic F127 (PEO(99)-PPO(67)-PEO(99)) was functionalized with (3
      isocyanatopropyl) triethoxysilane (IPTS) by reacting its terminal hydroxyl groups
      with the isocyanate. The silane-capped PEO-PPO-PEO triblock was characterized by
      (1)H-NMR, GPC, FT-IR and DSC and the rheological behavior of its aqueous
      solutions were studied. The silane-containing triblock retained the reverse
      thermo-responsive characteristics displayed by the original Pluronic. Over time,
      the ethoxysilane groups hydrolysed and created silanol moieties that subsequently
      condensated, crosslinking the material and generating hydrogels that exhibited
      gradually increasing mechanical properties. It was found that the higher the pH,
      the faster the process and the higher the viscosity levels attained. Finally, the
      ability of these gels to perform as matrices for drug delivery was exemplified by
      releasing metronidazole and methylene blue. Findings showed that while a 30% F127
      gel at 37 degrees C delivered all the drug within less than 3 days, F127di-IPTS
      gels completed the process at a much slower rate (up to 15 days).

PMID- 14962564
TI  - A device for the spatio-regional delivery of a photocurable drug formulation.
AB  - We devised a new transtissue drug-delivery system, based on a multiple-needle
      arrayed injector that has 36 long and short needles on the needle head, to
      administer the drug into local points of the target tissue at a well-controlled
      depth and pitch. A preliminary in vitro study, focusing the time-dependent depth
      profiling of protein injected in agarose gel as a model tissue using confocal
      laser scanning microscope, was conducted to evaluate the performance of the
      multiple-needle-arrayed injector coupled with photoreactive gelatin (styrenated
      gelatin: St-gelatin) as the sustained-release vehicle. Rhodamine-conjugated
      albumin, which was mixed with the St-gelatin buffer solution, was the model drug
      of the in vitro study, and the mixture was injected into agarose gel using the
      multiple-needle-arrayed injector by single injection, followed by visible-light
      irradiation to photocure the gelatin solution. Time-dependent distribution from
      the injected material into the surrounding agarose gel was observed using a
      confocal laser scanning microscope up to seven days. Injection of the drug
      material and concomitant withdrawal of the syringe (termed multirod method)
      enabled the long- and short-rod-like injections into the agarose gel at the same
      locations of the injected sites. The model drug gradually diffused throughout the
      agarose gel. In an in vivo study, the comparison of the efficacy of the
      angiogenic protein (bFGF: 10 microg for each) with placebo was performed using
      the non-ischemic hind limb model of rabbits. Four weeks after injection, a
      significant increase in the number of angiogenic capillaries was observed in the
      mixed St-gelatin/bFGF group compared with that of placebo. The multiple-needle
      arrayed injector coupled with a sustained-release vehicle may be an effective
      drug delivery system for realizing the spatio-regional distribution of angiogenic
      protein.

PMID- 14962565
TI  - Improved biological performance of Ti implants due to surface modification by
      micro-arc oxidation.
AB  - The surface of a titanium (Ti) implant was modified by micro-arc oxidation (MAO)
      treatment. A porous layer was formed on the Ti surface after the oxidation
      treatment. The phase and morphology of the oxide layer were dependent on the
      voltage applied during the oxidation treatment. With increasing voltage, the
      roughness and thickness of the film increased and the TiO(2) phase changed from
      anatase to rutile. During the MAO treatment, Ca and P ions were incorporated into
      the oxide layer. The in vitro cell responses of the specimen were also dependant
      on the oxidation conditions. With increasing voltage, the ALP activity increased,
      while the cell proliferation rate decreased. Preliminary in vivo tests of the MAO
      treated specimens on rabbits showed a considerable improvement in their
      osseointegration capability as compared to the pure titanium implant.

PMID- 14962566
TI  - Role of the water matric potential (psi(M)) and of equilibrium water content
      (EWC) on the water self-diffusion coefficient and on the oxygen permeability in
      hydrogel contact lenses.
AB  - This paper illustrates a new thermodynamic and kinetic model that describes the
      relationship between the water self-diffusion coefficient, D*(w/g), in hydrogel
      contact lenses, in terms of water matric potential (psi(M)) and equilibrium water
      content (EWC). Experimental measurements on commercial contact lenses yield water
      thermodynamic activity values ranging between 0.996 and 0.999. The corresponding
      psi(M) matric potential is, respectively, between -8 and -2J/mol at temperature
      35 degrees C. Comparison between water self-diffusion coefficients derived in
      this paper and those suggested by other authors shows that our values are greater
      (25%-50%) than the previous ones. The impact of this model on the nature of the
      oxygen permeability, pi, in the lenses has been evaluated and the changes of pi
      with psi(M) and EWC are predicted and compared with direct experimental
      measurements. For the contact lenses investigated, the oxygen permeability turns
      out to be only a quadratic function of equilibrium water content, despite the
      fact that the fraction of the "free" water molecules can be as high as 50%.

PMID- 14962567
TI  - Materials design in the performance of all-ceramic crowns.
AB  - Results from a systematic study of damage in material structures representing the
      basic elements of dental crowns are reported. Tests are made on model flat-layer
      specimens fabricated from various dental ceramic combinations bonded to dentin
      like polymer substrates, in bilayer (ceramic/polymer) and trilayer
      (ceramic/ceramic/polymer) configurations. The specimens are loaded at their top
      surfaces with spherical indenters, in simulation of occlusal function. The onset
      of fracture is observed in situ using a video camera system mounted beneath the
      transparent polymer substrate. Critical loads to induce fracture and deformation
      at the ceramic top and bottom surfaces are measured as functions of layer
      thickness and contact duration. Radial cracking at the ceramic undersurface
      occurs at relatively low loads, especially in thinner layers. Fracture mechanics
      relations are used to confirm the experimental data trends, and to provide
      explicit dependencies of critical loads in terms of key variables: material
      elastic modulus, hardness, strength and toughness; geometric-layer thicknesses
      and contact radius. Tougher, harder and (especially) stronger materials show
      superior damage resistance. Critical loads depend strongly (quadratically) on
      crown net thickness. The analytic relations provide a sound basis for the
      materials design of next-generation dental crowns.

PMID- 14962568
TI  - Effect of added gelatin on the properties of calcium phosphate cement.
AB  - This study investigates the effect of gelatin on the setting time, compressive
      strength, phase evolution and microstructure of calcium phosphate cement. The
      composite cement powder (about 18 wt% gelatin, and 82 wt% alpha-tricalcium
      phosphate) was prepared from the solid compound obtained by casting a gelatin
      aqueous solution containing alpha-tricalcium phosphate. 5 wt% of CaHPO(4) x
      2H(2)O were added to the powder before mixing with the liquid phase. Two cement
      formulations were prepared using two different liquid/powder ratios, and their
      properties compared with those of control samples, prepared without gelatin. The
      final setting time increases from 10 min to more than 45 min when the L/P ratio
      increases from 0.3 to 0.4 ml/g. The presence of gelatin accelerates the setting
      reaction, and improves the mechanical properties of the cements. The compressive
      strength increases with the setting reaction up to 10.7-14.0 MPa for the gelatin
      cements, whereas the control samples exhibit much lower values. The improved
      mechanical properties of the composite cements with respect to the controls can
      be related to their reduced total porosity and more compact microstructure.

PMID- 14962569
TI  - Nano-scale study of the nucleation and growth of calcium phosphate coating on
      titanium implants.
AB  - The nucleation and growth of a calcium phosphate (Ca-P) coating deposited on
      titanium implants from simulated body fluid was investigated by using atomic
      force microscopy (AFM) and environmental scanning electron microscopy (ESEM).
      Forty titanium alloy plates were assigned into two groups. One group with a
      smooth surface having a maximum roughness R(max) < 0.10 microm (s-Ti6Al4V) and a
      group with a rough surface with an R(max) < 0.25 microm (r-Ti6Al4V) were used.
      Titanium samples were immersed in SBF concentrated by five (SBF x 5) from 10 min
      to 5 h and examined by AFM and ESEM. Scattered Ca-P deposits of approximately 15
      nm in diameter appeared after only 10 min of immersion in SBF x 5. These Ca-P
      deposits grew up to 60-100 nm after 4 h on both s- and r-Ti6Al4V substrates. With
      increasing immersion time, the packing of Ca-P deposits with size of tens of
      nanometers in diameter formed larger globules and then a continuous Ca-P film on
      titanium substrates. A direct contact between the Ca-P coating and the Ti6Al4V
      surface was observed. The Ca-P coating was composed of nanosized deposits and of
      an interfacial glassy matrix. This interfacial glassy matrix might ensure the
      adhesion between the Ca-P coating and the Ti6Al4V substrate. In the case of s
      Ti6Al4V substrate, failures within this interfacial glassy matrix were observed
      overtime. Part of the glassy matrix remained on s-Ti6Al4V while part detached
      with the Ca-P film. The Ca-P coating detached from the smooth substrate, whereas
      the Ca-P film extended onto the whole rough titanium surface over time. In the
      case of r-Ti6Al4V, the Ca-P coating covered evenly the substrate after immersion
      in SBF x 5 for 5 h. The present study suggested that the heterogeneous nucleation
      of Ca-P on titanium was immediate and did not depend on the Ti6Al4V surface
      topography. The further growth and mechanical attachment of the final Ca-P
      coating strongly depended on the surface, for which a rough topography was
      beneficial.

PMID- 14962570
TI  - Event-related potentials elicited by non-target tones in an auditory oddball
      paradigm in schizophrenia.
AB  - It has been reported that in event-related potentials (ERPs) elicited by non
      target tones in oddball paradigms, the superimposition of a negative component on
      the descending slope of N100 depends on subjects' attention to the task. We
      tested the possibility that this attention-related change is abnormal for
      patients with schizophrenia. ERPs induced by non-target, frequent tones were
      measured for 52 patients and 31 healthy controls under two oddball conditions: a
      passive condition where the subjects were told to disregard the tones, and an
      active condition where they were instructed to respond to infrequent tones. For
      both groups, a negative component was superimposed from the descending slope of
      N100 to the end of P150 (latency, 120-200 ms) for the active condition. The peak
      latency of this attention-related negative component was longer for the patients
      than for the controls, while the amplitude showed no group difference. In
      addition, the active P150 for the patients was more enlarged than that for the
      controls. Furthermore, the active P150 amplitude for the patients correlated
      positively with the score for the negative symptom factor of the Positive and
      Negative Syndrome Scale. These findings suggest that the enlargement of non
      target P150 observed in conjunction with the latency prolongation of the
      attention-related negative component may be a biological marker for the severity
      of the negative symptoms in schizophrenia.

PMID- 14962571
TI  - An alternative baseline measure for calculation of the mismatch negativity (MMN)
      component of the event-related potential (ERP).
AB  - Mismatch negativity (MMN), a component of the event-related potential, reflects
      the processing associated with low-probability (deviant) stimuli over and above
      that required for high-probability (standard) stimuli. Occurring 100-250 ms post
      stimulus, MMN is evident in the enhanced negativity generated in response to
      deviant relative to standard stimuli. Traditionally, the MMN waveform is
      calculated by subtracting the averaged waveform of all standard stimuli from the
      averaged waveform of all deviant stimuli collected during the same test session.
      To investigate whether an unbroken, extended string of standard stimuli may
      minimize baseline processing, thereby resulting in a more robust measure of MMN,
      11 participants were exposed to two contiguous blocks of 1000 trials, each
      beginning with 60 uninterrupted standard stimuli followed by 940 randomized
      standard and deviant trials. Negativity related to standard stimuli was minimized
      in the average of uninterrupted standard stimuli from the second block of trials
      only while negativity related to uninterrupted standards in the first block of
      trials was increased relative to all other conditions. The present findings
      suggest that a familiar, uninterrupted string of standard stimuli, presented
      midway through an experimental session, may provide a useful alternative baseline
      for the calculation of MMN.

PMID- 14962572
TI  - Impaired P50 sensory gating in post-traumatic stress disorder secondary to urban
      violence.
AB  - Previous studies on sensory gating process in post-traumatic stress disorder
      (PTSD) have yielded conflicting results. To investigate sensory gating function
      in PTSD we performed a case-control study in a sample of 12 patients with PTSD
      related to urban violence, compared to 24 normal subjects and 12 schizophrenic
      subjects evaluating auditory mid-latency evoked potential P50 in a double-click
      paradigm as a measure of sensory gating. PTSD subjects showed poorer sensory
      gating as evidenced by higher P50 ratios as compared to normal subjects (85.6%
      vs. 44.4%, P=0.002). Test and conditioning amplitudes did not differ with
      statistical significance alone, suggesting a combined effect. Schizophrenic
      subjects had higher conditioning and marginally smaller test amplitudes when
      compared to healthy controls, but were not statistically different from PTSD
      subjects. The present study replicated previous findings of sensory gating
      dysfunction in PTSD. The pattern of this dysfunction resembles that found in
      schizophrenia, with both test and conditioning amplitudes possibly implicated.
      Further studies are still necessary to better understand the pathophysiology of
      this neurophysiological dysfunction and its nature as a trait or state marker.
      The P50 paradigm may also become an objective parameter to assess the effects of
      new treatments for PTSD.

PMID- 14962573
TI  - The coincidence between late non-phase-locked gamma synchronization response and
      saccadic eye movements.
AB  - The event-related response in the gamma (30-45 Hz) frequency band was studied in
      healthy subjects (n=45) viewing sequentially presented pictures from the
      International Affective Picture System. The distinct non-phase-locked gamma
      response was obtained in characteristic time window (200-400 ms) with clear-cut
      centro-parietal location. The strong coincidence between induced gamma
      oscillations and saccadic eye movements was revealed. We suggest that saccade
      related gamma increase is another manifestation of the phenomenon known as
      presaccadic spike potential, which is commonly registered over parietal scalp
      leads at 10-20 ms prior to saccade onset. It is hypothesized that late non-phase
      locked gamma synchronization mainly reflects activity of a system responsible for
      attentional tuning and motor planning/execution of saccadic eye movements.

PMID- 14962574
TI  - Automatic quantification of light sleep shows differences between apnea patients
      and healthy subjects.
AB  - A fully automatic method to quantify sleep depth during the night was developed
      in the present work. The method was tested using 20 all-night recordings from 10
      healthy control subjects and 10 sleep apnea patients. The results showed
      statistically significant differences in sleep depth between control subjects and
      sleep apnea patients. The overall sleep was lighter in apnea patients than in
      healthy control subjects, most likely indicating a disturbed sleep caused by
      apneas. The automatic parameters presented provide a method to quantify the light
      sleep and could in the future possibly be used in clinical sleep studies and
      follow-up of treatment.

PMID- 14962575
TI  - Diazepam attenuates conditioned histamine release in guinea pigs.
AB  - To clarify the possibility of pharmacological mediation on classical conditioning
      associated asthmatic response, the effect of diazepam on an odor-induced
      conditioned histamine release was investigated in ovalbumin (OA)-sensitized
      guinea pigs, i.e. a model of bronchial asthma. The animals received conditioning
      sessions in which an antigen (OA) as the unconditioned stimulus and an odor
      (dimethylsulfide) as the conditioned stimulus (CS) were simultaneously inhaled.
      After the animals were intraperitoneally injected with saline or diazepam (2.5 or
      5 mg/kg), they underwent exposure to the CS and blood collecting. This procedure
      was repeated three times in order that the animals would have each kind of
      injection. The animals injected with saline showed significantly higher levels of
      plasma histamine following the exposure to the CS as a conditioning effect
      compared with the baselines (P<0.05), whereas the group injected with diazepam (5
      mg/kg) did not indicate such elevations. The suppressing effect of diazepam on
      the conditioned histamine release was also confirmed by a multiple regression
      analysis (5 mg/kg) and an analysis of covariance (2.5 and 5 mg/kg), even after
      adjustments for several factors regarding immunological sensitization and
      conditionability. The present study suggests that diazepam attenuates a
      conditioned histamine release.

PMID- 14962576
TI  - Resting EEG in offspring of male alcoholics: beta frequencies.
AB  - This study examines the differences in beta (12-28 Hz) band power in offspring of
      male alcoholics from densely affected alcoholic families. We have attempted to
      investigate if the increase in beta power is a 'state' or 'trait' marker for
      alcoholism. This study also explores the gender differences in the expression of
      this potential risk marker. Absolute beta power in three bands-beta 1(12-16 Hz),
      beta 2 (16-20 Hz), and beta 3 (20-28 Hz)-in the eyes closed EEG of 171 high risk
      (HR) subjects who were offspring of male alcoholics and 204 low risk (LR)
      subjects with no family history of alcoholism, were compared for each gender
      separately using a repeated measures analysis of variance design. Alcoholic and
      non-alcoholic subjects within the high risk group were compared using a repeated
      measures design as a follow-up analysis. The present study demonstrated increased
      beta power in the resting EEG of offspring of male alcoholics. Male HR subjects
      had higher beta 1 (12-16 Hz) power and female HR subjects had increased power in
      beta 2 (16-20 Hz) and beta 3 (20-28 Hz) as compared with low risk participants.
      Female HR subjects also showed significantly increased beta 2 and beta 3 power if
      they had two or more alcoholic first-degree relatives when compared with HR
      females having only an affected father. Risk characteristics are expressed
      differentially in males and females and may be an index of differential
      vulnerability to alcoholism. The results indicate that increased EEG beta power
      can be considered as a likely marker of risk for developing alcoholism and may be
      used as a predictive endophenotype.

PMID- 14962577
TI  - Nonlinear and linear EEG complexity changes caused by gustatory stimuli in
      anorexia nervosa.
AB  - The objective of the present study was to investigate the effects of pleasant and
      unpleasant gustatory stimuli on nonlinear and linear complexity measures of the
      EEG in healthy controls and in anorexia nervosa (AN) patients. The subjects were
      exposed to unpleasant (bitter tea) and pleasant (chocolate) gustatory stimuli for
      2 min. Multichannel EEG was recorded and the dimensional complexity (point
      correlation dimension) and Omega complexity were calculated from the EEG epochs
      corresponding to the above taste conditions. In AN patients lower-dimensional
      complexity was observed in the majority of recording sites than that seen in
      controls, independent of taste conditions. Higher Omega complexity was seen in
      control subjects in the left side irrespective of taste effects. No such
      hemispheric difference was observed in AN. The lower-dimensional complexity seen
      in AN patients may be caused by long-lasting effects of malnutrition. The lack of
      a significant Omega complexity change in response to exposure of sweet taste in
      the left side seen in AN patients may correspond to a decreased sensitivity to
      such stimuli in these subjects.

PMID- 14962578
TI  - The influence of auditory background stimulation (Mozart's sonata K. 448) on
      visual brain activity.
AB  - Twenty individuals solved a visual oddball task in two response conditions: while
      listening to the Mozart's sonata K. 448, and while listening to nothing. The
      recorded event-related potentials (ERP) were analyzed in the time and frequency
      domains. In the music response condition the ERP peak latencies on the left
      hemisphere increased, whereas on the right hemisphere a decrease of peak
      latencies as compared with the silence response condition was observed. In the
      theta, lower-1 alpha and gamma band increases in induced event-related coherences
      were observed while respondents solved the oddball task and listened to music,
      whereas a decoupling of brain areas in the gamma band was observed in the silence
      response condition. It is suggested that auditory background stimulation can
      influence visual brain activity, even if both stimuli are unrelated.

PMID- 14962580
TI  - A timely re-examination of drug polymorphism in pharmaceutical development and
      regulation.

PMID- 14962581
TI  - General principles of pharmaceutical solid polymorphism: a supramolecular
      perspective.
AB  - The diversity of solid-state forms that an active pharmaceutical ingredient (API)
      may attain relies on the repertoire of non-covalent interactions and molecular
      assemblies, the range of order, and the balance between entropy and enthalpy that
      defines the free energy landscape. It is recognized that crystallization is
      associated with molecular recognition events that lead to self-assembly, and that
      pharmaceutical function and thermodynamic stability can be altered with a slight
      change in the interacting molecules or their molecular network motifs. Our
      current understanding of pharmaceutical solids in terms of molecular recognition
      and complementarity provides new insights into the design and function of single
      and fully miscible, multiple-component solids with varying degrees of order, from
      amorphous to crystalline states, and in this way is leading the path to
      supramolecular pharmaceutics. This review describes pharmaceutical solids in
      terms of supramolecular chemistry and crystal engineering concepts, and discusses
      the events that control crystallization and solid phase transformations.

PMID- 14962582
TI  - High-throughput crystallization: polymorphs, salts, co-crystals and solvates of
      pharmaceutical solids.
AB  - The concepts of high-throughput (HT) screening and combinatorial synthesis have
      been integrated into the pharmaceutical discovery process, but are not yet
      commonplace in the pharmaceutical development arena. Emerging strategies to speed
      pharmaceutical development and capture solid form diversity of pharmaceutical
      substances have resulted in the emergence of HT crystallization technologies. The
      primary type of diversity often refers to polymorphs, which are different crystal
      forms of the same chemical composition. However, diverse salt forms, co-crystals,
      hydrates and solvates are also amenable to study in HT crystallization systems.
      The impact of form diversity encompasses issues of stability and bioavailability,
      as well as development considerations such as process definition, formulation
      design, patent protection and regulatory control. This review highlights the
      opportunities and challenges of HT crystallization technologies as they apply to
      pharmaceutical research and development.

PMID- 14962583
TI  - The computational prediction of pharmaceutical crystal structures and
      polymorphism.
AB  - A computational method of predicting all the polymorphs of an organic molecule
      would be a valuable complement to polymorph screening in the developmental phase.
      Such a computational method is in its early stages of development, and the
      current methodologies, which are based on searches for the most stable lattice
      structure, are critically reviewed. This crude thermodynamic approach generally
      overestimates the propensity for polymorphism, at least for most of the molecules
      studied so far, showing the need to model kinetic effects as well as to refine
      the thermodynamic models. Although the ultimate goal of these studies is still
      far off, computational predictions of crystal structures have proved useful in
      aiding the characterisation of polymorphs from powder X-ray data, and in
      providing insights into the range of types of packing that may be adopted by a
      given molecule. Thus, computational studies already have the potential to be a
      valuable tool in pharmaceutical solid state science.

PMID- 14962584
TI  - Impact of solid state properties on developability assessment of drug candidates.
AB  - Solid state properties including polymorphism, solvate and salt formation can
      have a profound impact on two of the most important properties that are essential
      to the successful development of drug candidates: solubility and stability. To
      enable meaningful evaluations of drug candidates for their development risks,
      often referred to as developability, and provide input to the molecular design
      regarding the "drug-like" properties, one must take into account the impact of
      solid state properties on solubility and stability. This review examines the
      importance of solid state properties and their relationship to developability
      criteria. Phase appropriate characterization strategies and appropriate salt and
      crystal form screening and selection processes are discussed. These strategies
      and processes should balance the need for speed and throughput of modern
      discovery with the quality of data essential to the adequate developability
      assessment. Specific examples are given to illustrate the importance of
      understanding the solid state properties and their impact on developability.

PMID- 14962585
TI  - Drug polymorphism and dosage form design: a practical perspective.
AB  - Formulators are charged with the responsibility to formulate a product which is
      physically and chemically stable, manufacturable, and bioavailable. Most drugs
      exhibit structural polymorphism, and it is preferable to develop the most
      thermodynamically stable polymorph of the drug to assure reproducible
      bioavailability of the product over its shelf life under a variety of real-world
      storage conditions. There are occasional situations in which the development of a
      metastable crystalline or amorphous form is justified because a medical benefit
      is achieved. Such situations include those in which a faster dissolution rate or
      higher concentration are desired, in order to achieve rapid absorption and
      efficacy, or to achieve acceptable systemic exposure for a low-solubility drug.
      Another such situation is one in which the drug remains amorphous despite
      extensive efforts to crystallize it. If there is no particular medical benefit,
      there is less justification for accepting the risks of intentional development of
      a metastable crystalline or amorphous form. Whether or not there is medical
      benefit, the risks associated with development of a metastable form must be
      mitigated by laboratory work which provides assurance that (a) the largest
      possible form change will have no substantive effect on product quality or
      bioavailability, and/or (b) a change will not occur under all reasonable real
      world storage conditions, and/or (c) analytical methodology and sampling
      procedures are in place which assure that a problem will be detected before
      dosage forms which have compromised quality or bioavailability can reach
      patients.

PMID- 14962586
TI  - Applications of process analytical technology to crystallization processes.
AB  - Crystallizations of pharmaceutical active ingredients, particularly those that
      posses multiple polymorphic forms, are among the most critical and least
      understood pharmaceutical manufacturing processes. Many process and product
      failures can be traced to a poor understanding and control of crystallization
      processes. The Food and Drug Administration's process analytical technology (PAT)
      initiative is a collaborative effort with industry to introduce new and efficient
      manufacturing technologies into the pharmaceutical industry. PAT's are systems
      for design, analysis, and control of manufacturing processes. They aim to assure
      high quality through timely measurements of critical quality and performance
      attributes of raw materials, in-process materials, and final products.
      Implementation of PAT involves scientifically based process design and
      optimization, appropriate sensor technologies, statistical and information tools
      (chemometrics), and feedback process control strategies working together to
      produce quality products. This review introduces the concept of PAT and discusses
      its application to crystallization processes through review of several case
      studies. A variety of in situ analytical methods combined with chemometric tools
      for analysis of multivariate process information provide a basis for future
      improvements in modeling, simulation, and control of crystallization processes.

PMID- 14962587
TI  - Phase transformation considerations during process development and manufacture of
      solid oral dosage forms.
AB  - The quality and performance of a solid oral dosage form depends on the choice of
      the solid phase, the formulation design, and the manufacturing process. The
      potential for process-induced solid phase transformations must be evaluated
      during design and development of formulations and manufacturing processes. This
      article briefly reviews the basic principles of polymorphism, defines the classes
      of phase transformation and the underlying transformation mechanisms, and
      discusses respective kinetic factors. The potential phase transformations
      associated with common unit operations employed in manufacturing solid oral
      dosage forms are highlighted. Specific examples are given to illustrate the
      importance of solid phases, and process-induced phase transitions in formulation
      and process development.

PMID- 14962588
TI  - Polymorphism in generic drug product development.
AB  - The affect of polymorphism in the development of generic drug products is
      discussed. The desired polymorphic form is used based upon the ability to
      manufacture a bioequivalent product. The critical issues are control of the
      polymorphic form of the drug substance and the dissolution behavior of the drug
      product.

PMID- 14962589
TI  - Regulatory considerations of pharmaceutical solid polymorphism in Abbreviated New
      Drug Applications (ANDAs).
AB  - A sponsor of an Abbreviated New Drug Application (ANDA) must have information to
      show that the proposed generic product and the innovator product are both
      pharmaceutically equivalent and bioequivalent, and therefore, therapeutically
      equivalent. Many pharmaceutical solids exist in several crystalline forms and
      thus exhibit polymorphism. Polymorphism may result in differences in the physico
      chemical properties of the active ingredient and variations in these properties
      may render a generic drug product to be bioinequivalent to the innovator brand.
      For this reason, in ANDAs, careful attention is paid to the effect of
      polymorphism in the context of generic drug product equivalency. This review
      discusses the impact of polymorphism on drug product manufacturability, quality,
      and performance. Conclusions from this analysis demonstrate that pharmaceutical
      solid polymorphism has no relevance to the determination of drug substance
      "sameness" in ANDAs. Three decision trees for solid oral dosage forms or liquid
      suspensions are provided for evaluating when and how polymorphs of drug
      substances should be monitored and controlled in ANDA submissions. Case studies
      from ANDAs are provided which demonstrate the irrelevance of polymorphism to the
      determination of drug substance "sameness". These case studies also illustrate
      the conceptual framework from these decision trees and illustrate how their
      general principles are sufficient to assure both the quality and the therapeutic
      equivalence of marketed generic drug products.

PMID- 14962592
TI  - Can the RNA of the cowpea chlorotic mottle virus be released through a channel by
      means of free diffusion? A test in silico.
AB  - Cowpea chlorotic mottle virus (CCMV), a plant virus which is member of the
      Bromoviridae family, is used as a model for the diffusion of a random, short,
      single stranded RNA, [5'-R(PGpGpApCpUpUpCpGpGpUpCpC)-3')], through a channel on
      the pseudo-three-fold axis using molecular dynamic simulations. This proposition
      is based the fact that CCMV undergoes a dynamic structural transition as a
      response to changes of pH, temperature and ionic strength. Results indicate that
      the RNA looses its secondary structure and moves into the capside channel by free
      diffusion. These results are congruent with the hypothesis suggesting that the
      CCMV capside does not have to dissolve in order to release the RNA into the host.

PMID- 14962593
TI  - Scanning tunneling spectroscopy investigation of self-assembled plastocyanin
      mutants onto gold substrates under controlled environment.
AB  - The study of the electronic conduction through plastocyanin (PC) mutants
      assembled on a gold surface has been addressed by scanning tunneling
      spectroscopy. The two mutants exploit a single thiol group (PCSH) or a disulfide
      bridge (PCSS) to covalently bind at gold surface. The I-V measurements were
      performed by positioning the STM tip on top of a single molecule and sweeping the
      bias potential between +/-1 V, under both ambient and controlled atmosphere. For
      PCSS, under ambient conditions, asymmetric I-V characteristics were obtained,
      which disappear under nitrogen atmosphere. PCSH, instead shows a symmetric I-V
      relation in air and under nitrogen environment. Here, as factors underlying this
      distinct electron conductive behaviour, a potential role for hydration water
      molecules and for copper redox levels are discussed.

PMID- 14962594
TI  - Dynamics of interaction of vitamin C with some potent nitrovasodilators, S
      nitroso-N-acetyl-d,l-penicillamine (SNAP) and S-nitrosocaptopril (SNOCap), in
      aqueous solution.
AB  - The reductive decomposition of both SNAP and SNOCap by ascorbate in aqueous
      solution (in the presence of EDTA) was thoroughly investigated. Nitric oxide (NO)
      release from the reaction occurs in an ascorbate concentration and pH dependent
      manner. Rates and hence NO release increased drastically with increasing pH,
      signifying that the most highly ionized form of ascorbate is the more reactive
      species. The experiments were monitored spectrophotometrically, and second-order
      rate constants calculated at 37 degrees C for the reduction of SNAP are
      k(b)=9.81+/-1.39 x 10(-3) M(-1) s(-1) and k(c)=662+/-38 M(-1) s(-1) and for
      SNOCap are k(b)=2.57+/-1.29 x 10(-2) M(-1) s(-1) and k(c)=49.7+/-1.3 M(-1) s(-1).
      k(b) and k(c) are the second-order rate constants via the ascorbate monoanion (HA
      ) and dianion (A2-) pathways, respectively. Activation parameters were also
      calculated and are DeltaHb++ =93+/-7 kJ mol(-1), DeltaSb++ =15+/-2 J K(-1) mol(
      1) and DeltaHc++ =51+/-5 kJ mol(-1), DeltaSc++ =-28+/-3 J K(-1) mol(-1) with
      respect to the reactions involving SNAP. Those for the reaction between SNOCap
      and ascorbate were calculated to be DeltaHb++ =63+/-11 kJ mol(-1), DeltaSb++ =
      71+/-20 J K(-1) mol(-1) and DeltaHc++ =103+/-7 kJ mol(-1), DeltaSc++ =118+/-8 J
      K(-1) mol(-1). The effect of Cu2+/Cu+ ions on the reductive decompositions of
      these S-nitrosothiols was also investigated in absence of EDTA. SNOCap exhibits
      relatively high stability at near physiological conditions (37 degrees C and pH
      7.55) even in the presence of micromolar concentrations of Cu2+, with
      decomposition rate constant being 0.011 M(-1) s(-1) in comparison to SNAP which
      is known to be more susceptible to catalytic decomposition by Cu2+ (second-order
      rate constant of 20 M(-1) s(-1) at pH 7.4 and 25 degrees C). It was also observed
      that the reductive decomposition of SNAP is not catalyzed by alkali metal ions,
      however, there was an increase in rate as the ionic strength increases from 0.2
      to 0.5 mol dm(-3) NaCl.

PMID- 14962595
TI  - An overview of the biophysical applications of atomic force microscopy.
AB  - The potentialities of the atomic force microscopy (AFM) make it a tool of
      undeniable value for the study of biologically relevant samples. AFM is
      progressively becoming a usual benchtop technique. In average, more than one
      paper is published every day on AFM biological applications. This figure
      overcomes materials science applications, showing that 17 years after its
      invention, AFM has completely crossed the limits of its traditional areas of
      application. Its potential to image the structure of biomolecules or bio-surfaces
      with molecular or even sub-molecular resolution, study samples under
      physiological conditions (which allows to follow in situ the real time dynamics
      of some biological events), measure local chemical, physical and mechanical
      properties of a sample and manipulate single molecules should be emphasized.

PMID- 14962596
TI  - Non-polar interactions between cholesterol and phospholipids: a molecular
      dynamics simulation study.
AB  - A 15-ns molecular dynamics simulation of the fully hydrated
      dimyristoylphosphatidylcholine-cholesterol (DMPC-Chol) bilayer containing
      approximately 22 mol% Chol was carried out. An 8-ns trajectory was analysed to
      investigate the effect of Chol on the chain packing in the bilayer core. While
      the packing of DMPC chains on the smooth alpha-face side of the Chol ring is
      similar to that in the pure DMPC bilayer, the packing on the rough beta-face side
      is less regular and less tight. Two methyl groups located on the Chol beta-face
      disturb the packing; in effect, van der Waals (vdW) interactions between Chol
      rings and DMPC chains are weaker than the ones between sole DMPC chains. VdW
      interactions between an alkyl chain of DMPC and an isooctyl tail of Chol are
      similarly strong as those between two DMPC chains.

PMID- 14962597
TI  - The condition for pseudo-first-order kinetics in enzymatic reactions is
      independent of the initial enzyme concentration.
AB  - The linearization of the Michaelis-Menten reaction by pseudo-first-order kinetics
      is revised. A phase-plane analysis allows the derivation of a new condition for
      its validity that is directly linked to the reaction efficiency, and contrary to
      widely established knowledge, is independent of the initial enzyme concentration.

PMID- 14962598
TI  - Aggregation kinetics of bovine serum albumin studied by FTIR spectroscopy and
      light scattering.
AB  - To investigate which type of structural and conformational changes is involved in
      the aggregation processes of bovine serum albumin (BSA), we have performed
      thermal aggregation kinetics in D(2)O solutions of this protein. The tertiary
      conformational changes are followed by Amide II band, the secondary structural
      changes and the formation of beta-aggregates by the Amide I' band and, finally,
      the hydrodynamic radius of aggregates by dynamic light scattering. The results
      show, as a function of pD, that: tertiary conformational changes are more rapid
      as pD increases; the aggregation proceeds through formation of ordered aggregates
      (oligomers) at pD far from the isoelectric point of the protein; disordered
      structures add as the pD decreases. Moreover, beta-aggregates seem to contribute
      only to oligomers formation, as showed by the good correlation between kinetics
      of scattering intensity and IR absorption intensity. These results indicate for
      BSA a general mechanism of aggregation composed by partial unfolding of the
      tertiary structure and by the decrease of alpha-helix and random coil contents in
      favor of beta-sheet aggregates. This mechanism strictly depends on pD and gives
      rise to almost two distinct types of macromolecular aggregates.

PMID- 14962599
TI  - Trapped water of human erythrocytes and its application in cryopreservation.
AB  - The novel differential scanning calorimetry method as a technique for determining
      human red cell volume during freezing process has been reexamined and has been
      shown to provide a final erythrocyte volume to be 53% of its isotonic value after
      freezing from 0 to -40 degrees C. A new type of electronic particle counter
      (Multisizer 3, Beckman Coulter Inc., USA) was used to measure cell volume changes
      in response to equilibration in anisotonic media, and which gave out an
      equilibrated volume to be 57% of cell isotonic value in solution of 3186 mOsm.
      Both of these results indicate that 34-40% of intracellular water is trapped and
      is unavailable for participation in osmotic shifts. These findings are consistent
      with the published data that at least 20-32% (v/v) of the isotonic cell water is
      retained within RBCs. Then the application of trapped water in both simulation of
      freezing models and freezing-drying control was pointed out.

PMID- 14962600
TI  - A fast and accurate procedure to collect and analyze unfolding fluorescence
      signal: the case of dystroglycan domains.
AB  - Monitoring the fluorescence signal upon unfolding often represents a very
      effective method to rapidly retrieve the first preliminary structural information
      on a protein domain. The relationship between intrinsic fluorescence signals and
      unfolding of proteins are discussed, including several practical considerations
      for properly setting fluorescence experiments and the phenomenological equations
      required to analyze the spectra. In particular, a fast and accurate method which
      allows to minimize the deleterious effect of photobleaching is provided. A number
      of unfolding reactions relative to immunoglobulins (IgG and IgM) and to the
      different domains of the adhesion molecule dystroglycan are presented. Special
      attention is dedicated to a alpha-dystroglycan immunoglobulin-like domain showing
      a "reverse" behavior of the fluorescence signal as a function of the denaturing
      agent concentration.

PMID- 14962601
TI  - Percutaneous management of breast abscesses. An experience of 39 cases.
AB  - This is a review of our experience with percutaneous drainage by means of needle
      aspiration or catheter drainage of breast abscesses under ultrasound (US)
      guidance, and a suggested management algorithm. A retrospective study of the 39
      patients (36 women, 3 men; mean age: 28.9 years) with breast abscesses who were
      treated by percutaneous US-guided procedures over a period of 13 years (1989 to
      2002) was carried out. Of the 36 women, 34 were nonlactating and two lactating.
      Needle aspiration was used in the cases of fluid collections < or = 3 cm and
      catheter drainage in fluid collections of > 3 cm. Postdrainage care and US
      evolutive controls were carried out on an outpatient basis. Fine-needle
      aspiration cytology was performed in masses unresolved after postdrainage.
      Mammography was performed in patients over 30 years old. In all cases, US
      examination revealed images of fluid collection. A single needle aspiration was
      sufficient in 19 cases; 3 patients needed a second aspiration to resolve the
      breast abscess. A total of 15 cases were resolved by means of percutaneous
      catheter drainage. In 2 of the 17 patients who underwent catheter drainage, the
      mass persisted postdrainage; histologic findings showed a chronic abscess
      requiring surgical intervention in one and a breast carcinoma in the second. Mean
      follow-up was 8.4 months. Recurrence of breast abscess occurred in 4 patients,
      and these were resolved by surgical excision. Percutaneous drainage procedures in
      breast abscesses are a safe and effective alternative to incision and drainage.
      Needle aspiration is employed in cases of small abscesses and catheter drainage
      in abscesses larger than 3 cm. Although, in chronic abscesses, the treatment of
      choice is surgical excision, percutaneous drainage remains as an intermediate
      therapeutic option.

PMID- 14962602
TI  - Uterine volume in adolescents.
AB  - The objective of the present study was to determine the uterine volume of
      adolescents by ultrasonography, and to correlate it with pregnancy during
      adolescence and with the immaturity of the female genital tract for pregnancy and
      delivery. A transverse observational study was conducted on 828 patients who were
      10 to 40 years old by transabdominal ultrasonography and were divided into two
      groups: group 1 consisted of 477 (57.6%) adolescents and group 2 consisted of 351
      (42.3%) women 20 to 40 years old. Uterine volume increased with the presence of
      menarche, age and parity (p < 0.05). Nulliparous and primiparous adolescents
      younger than 18 years old had a smaller uterine volume, 41.3 +/- 17.9 and 51.6 +/
      19.7 cm(3), respectively, than nulliparous and primiparous women 20 to 40 years
      old (p < 0.001). However, secundiparous adolescents had a uterine volume of 62.6
      +/- 20.6 cm(3), which was significantly similar to the uterine volume of women 20
      to 40 years old (p = 0.22). The differences in uterine volume between adolescents
      younger than 18 years old or with less than two deliveries and women who were 20
      to 40 years old may be due to immaturity of the female genital tract for
      pregnancy and delivery among younger women, with a consequent higher incidence of
      preterm deliveries in this group.

PMID- 14962603
TI  - A limited range of measures of 2-D ultrasound correlate with 3-D MRI cerebral
      volumes in the premature infant at term.
AB  - Two-dimensional (2-D) cranial ultrasound (US) is the principal method for the
      detection of cerebral injury in the newborn. The aim of this study was to compare
      2-D sonographic methods with more advanced 3-D magnetic resonance imaging (MRI)
      for assessing brain structure. From July 1998 to November 2000, we conducted a
      prospective methodological study comparing 2-D cranial sonographic measurements
      with volumes of cerebrospinal fluid (CSF), white matter, grey matter and total
      volume of brain obtained using 3-D MRI. The study group comprised 63 infants (33
      boys), mean gestational age 28 weeks (range 23 to 33 weeks), with imaging studies
      within 15 days of term equivalent. The highest correlations were between the
      occipital horn length and total brain volume (R2 = 0.30), the subarachnoid space
      and both CSF volume (R2 = 0.46) and relative intracranial space occupied by brain
      tissue (R2 = 0.48). Only 8 (30%) of the 2-D cranial US measures demonstrated good
      reproducibility. 2-D sonographic measures are limited in reflecting variations in
      overall cerebral structure, although certain measures, such as subarachnoid space
      and occipital lobe measures, may be useful in better defining cerebral
      parenchymal and CSF volumes.

PMID- 14962604
TI  - Alterations in thyroid Doppler arterial resistance indices, volume and hormones
      in cirrhosis: relationships with splanchnic haemodynamics.
AB  - The hypothesis of thyroid involvement in the haemodynamic alterations of
      cirrhosis was evaluated. We measured thyroid volume (thrV), free
      triiodiothyronine (FT3), free thyroxin (FT4), thyroid stimulating hormone (TSH),
      resistance index (thrRI) and pulsatility index (thrPI) in the inferior thyroid
      artery in 45 cirrhotic patients of different aetiologies and Child class, and in
      13 healthy subjects. Portal vein velocity, flow, diameter and hepatic, splenic,
      and renal arterial resistance indices were also evaluated. ThrV was increased in
      Child-C patients (p < 0.05). FT3 was decreased in cirrhotic patients (p < 0.05),
      TSH and FT4 were not different. ThrPI and thrRI were increased in cirrhotic
      patients (thrPI: 1.01 +/- 0.15 vs. 0.81 +/- 0.11; thrRI: 0.62 +/- 0.05 vs. 0.53
      +/- 0.04; p < 0.01) and were inversely correlated with FT3 (p < 0.05), and
      directly correlated with hepatic, splenic and renal resistance indices (p <
      0.01). In conclusion, thyroid is involved, primarily and secondarily, in the
      haemodynamic alterations of cirrhosis; a reduction in vasodilator FT3 may play a
      role in the pathophysiology.

PMID- 14962605
TI  - Volumetric tumor measurement using three-dimensional ultrasound: in vitro phantom
      study on measurement accuracy under various scanning conditions.
AB  - Factors influencing volumetric tumor measurement using 3-D ultrasound (US) were
      investigated. A 3-D US unit equipped with 4- to 8-MHz curved-array and 5- to 10
      MHz linear-array mechanical volume transducers, and a US phantom made of 20 ham
      pieces (8.6 approximately 10.5 mL) embedded in agar gel that simulated
      hyperechoic tumors, were used. Volumetric tumor measurement was significantly
      affected by the position of US focus and tumor depth. When focus was at 2 cm and
      8 cm below the transducer, 5-cm-deep tumors were measured 5.6% +/- 2.8% (mean +/-
      SD) and 8.3% +/- 2.2% bigger, respectively, than when focus was at 5 cm below the
      transducer, the same position as tumors (p < 0.01). Tumors were measured 11.8% +/
      2.9% bigger when they were 8-cm deep below the transducer than when they were 5
      cm deep below the transducer (p < 0.001). Setting focus at the same position as
      tumors and keeping tumor depth consistent during serial 3-D US examinations may
      be necessary for reliable volumetric assessment of tumors.

PMID- 14962606
TI  - Application of validated ultrasound indices to investigate erythrocyte
      aggregation in pigs. Preliminary in vivo results.
AB  - Although some studies concerning the ultrasound (US) characterization of
      erythrocyte aggregation reported in the literature have been conducted in vivo,
      none of them has led to quantitative indices. To achieve this objective, we first
      finalized a method on a hydrodynamic bench. Particularly, we define a kinetic
      protocol consisting of applying a 200 s(-1) shear rate followed up by a rapid
      decrease to reach a residual shear rate between 0 to 32 s(-1). From the
      backscattered intensity curve recorded all along the kinetic procedure, US
      dynamic parameters were defined and validated by correlation with reference laser
      indices obtained with the same model suspensions of erythrocytes (different
      concentrations of dextran 70 kD). A particular interesting behavior has been
      demonstrated when studying aggregation vs. the residual shear rate applied. The
      aim of the present study was to test the applicability of this aggregation
      kinetics protocol during in vivo investigations in pigs and possibly to recover
      the same aggregating behavior. The backscattered intensity was recorded all along
      the kinetic procedure as defined in vitro. Taking the derivative of the velocity
      profile recorded on 56 electronic windows, the shear rate was finely computed in
      the same measurement window where the backscattered intensity was calculated.
      Each US parameter could, therefore, be correlated with the residual shear rate
      corresponding to the same depth of measurement. We found that the blood
      aggregation behavior was identical to that observed in vitro. Apparently, a
      specific range of residual shear rates accelerates the activation of the
      aggregation process and the final aggregation level attained.

PMID- 14962607
TI  - Echogenicity variations from porcine blood I: the "bright collapsing ring" under
      pulsatile flow.
AB  - The temporal and radial variations of the echogenicity from porcine blood were
      investigated using a linear M12L transducer with a GE LOGIQ 700 Expert system.
      The "bright collapsing ring" (BRCR) phenomenon, a bright echogenic ring
      converging from the periphery to the center of the tube wall and eventually
      collapsing during a pulsatile cycle in cross-sectional B-mode images, was
      observed from porcine blood in a mock flow loop within a 0.95-cm diameter tube
      under certain flow conditions. The BRCR phenomenon from porcine blood was
      stronger as the peak speed was increased from 10 to 25 cm/s, and the mean
      echogenicity and the "black hole" (BLH) phenomenon, a central echo-poor zone
      surrounded by a bright hyperechoic zone, became weaker. As stroke rate was
      increased from 20 to 60 beats/min (bpm), both the BRCR and the BLH phenomena
      became weaker. These two phenomena were observed at three transmitting
      frequencies (9, 11 and 13 MHz). As hematocrit was increased from 12 to 45%, the
      BRCR phenomenon became more apparent. The nonlinear behavior of backscatter as a
      function of hematocrit reaching a maximum at hematocrit of 10 approximately 20%
      was observed near the tube wall, but it changed at the center of the tube,
      indicating the importance of hemodynamics on the ultrasonic backscatter from
      flowing blood. The combined effects of shear rate and acceleration on red blood
      cell aggregation are suggested as a possible mechanism for these phenomena.

PMID- 14962608
TI  - Short-term results of 89 cases of rectal carcinoma treated with high-intensity
      focused ultrasound and low-dose radiotherapy.
AB  - The purpose of this study was to assess the therapeutic effects and safety of
      combined high-intensity focused ultrasound (HIFU) and low-dose radiotherapy for
      the treatment of rectal carcinoma. A total of 89 cases of rectal carcinoma,
      including 20 cases of primary rectal carcinoma and 69 cases of recurrent rectal
      carcinoma after radical rectectomy, were treated with HIFU from July 1998 to
      December 2000. Of these, 23 patients had follow-up for more than 1 year. There
      was complete response (CR) in 22.5%, partial response (PR) in 64.0% and no change
      (NC) in 13.5%. There were no complications, such as skin burn, visceral
      perforation or hemorrhage, etc. In the 23 cases with follow-up, the 1-year
      survival rate was 87.0% (20 of 23) and the 2-year survival rate was 80.0% (12 of
      15). It was concluded that HIFU is a new method to treat rectal carcinoma that
      has remarkable therapeutic effect and is safe, with no significant side effects.

PMID- 14962609
TI  - Attenuation of porcine tissues in vivo after high-intensity ultrasound treatment.
AB  - The attenuation of ultrasound (US) waves in biologic tissues is an important
      determinant of energy absorption and wave propagation; thus, important in
      optimization of high-intensity focused US (HIFU) therapy. We measured attenuation
      of selected porcine tissues (liver, spleen and abdominal wall) in vivo in the
      frequency range of 1 to 5 MHz, using the pulse-transmission method, before and
      after HIFU treatment. In all tissues, an increase in attenuation was observed
      with increasing frequency. The attenuation coefficient was higher in HIFU-treated
      tissues than in the untreated tissues. The lowest attenuation was measured in the
      liver, both in normal and HIFU-treated cases. Mechanisms that may be responsible
      for the observed attenuation coefficient increase in HIFU-treated tissues include
      thermally induced change in the tissue macromolecular structure and presence of
      gas/vapor bubbles due to cavitation and/or boiling.

PMID- 14962610
TI  - Optical monitoring of ultrasound-induced bioeffects in glass catfish.
AB  - This study is an investigation of the therapeutic ultrasound (US) effects on the
      blood vessels of optically transparent fish in vivo. Although many investigators
      have characterized cavitation in vivo using remote-sensing methods (i.e.,
      measuring the acoustic emissions caused by oscillating bubbles) very few have
      made direct observations of cavitation-induced damage. Anesthetized glass
      catfish, which are optically transparent, was injected with the contrast agent,
      Optison, and then insonified at pressures that ranged from 0.5-10 MPa (peak
      negative pressures). Two focused transducers were used in these experiments to
      cover a frequency range of 0.7-3.3 MHz. Sonications were pulsed with pulse
      durations of 100, 10, 1, 0.1 and 0.01 ms and a pulse repetition frequency (PRF)
      of 1 Hz. The entire length of one sonication at a specific pressure level was 20
      s. An inverted microscope combined with a digital camera and video monitor were
      used optically to monitor and record US interaction with the blood vessels in the
      tail of the anesthetized fish at 200x magnification. The effects of the burst
      sonication were analyzed visually at each pressure level. For the 1.091-MHz
      sonications, the first type of damage that occurred due to the US interaction was
      structural damage to the cartilage rods that comprise the tail of the fish, and
      was characterized by a disintegration of the lining of the rod. Damage to the
      rods occurred, starting at 3.5 MPa, 3.1 MPa, 4.1 MPa and 5.5 MPa for the 100-ms,
      10-ms, 1-ms and 100-micros sonications, respectively. The formation of large gas
      bubbles was observed in the blood vessels of the fish at threshold values of 3.8
      MPa, 3.8 MPa and 5.3 MPa, for the 100-ms, 10-ms and 1-ms sonications,
      respectively. Neither gas bubble formation nor hemorrhaging was observed during
      100-micros sonications. Bubble formation was always accompanied by an increase of
      damage to the rods at the area surrounding the bubble. At 1.091 MHz, petechial
      hemorrhage thresholds were observed at 4.1 MPa, 4.1 MPa and 6.1 MPa,
      respectively, for the three pulse durations. The thresholds for damage were the
      lowest for the 0.747-MHz sonications: they were 2.6 MPa for damage to the rods,
      3.7 MPa for gas bubble formation and 2.4 MPa for hemorrhaging.

PMID- 14962611
TI  - Ultrasound contrast agents can influence the respiratory burst activity of human
      neutrophil granulocytes.
AB  - Activated leucocytes can bind and, subsequently, phagocytose microbubbles that
      are used as ultrasound (US) contrast agents. The purpose of this study was to
      investigate whether or not microbubbles can influence the inflammatory response
      of human neutrophil granulocytes. Granulocytes isolated from healthy volunteers
      were activated with various stimuli, for example, the bacterial peptide N-formyl
      methyonyl-leucyl-phenylalanine (fMLP), the calcium ionophore A23187, the protein
      kinase C activator phorbol myristate acetate (PMA) and the cytokine tumor
      necrosis factor alpha (TNF-alpha), and incubated with albumin or phospholipid
      microbubbles. Neutrophil respiratory burst activity and elastase release were
      quantified. Albumin (Optison) and phospholipid (SonoVue) contrast agents induced
      an extensive oxidative response of human granulocytes to all the stimuli used,
      and these effects could be significantly impaired by preincubation of the cells
      with cytochalasin B. Left heart contrast agents used for contrast-enhanced US
      assessment can activate human neutrophil granulocytes, inducing an extensive
      respiratory burst to secondary stimuli. The potential clinical relevance of this
      effect needs to be elucidated.

PMID- 14962612
TI  - Impact of myocardial contrast echocardiography on vascular permeability:
      comparison of three different contrast agents.
AB  - Microvascular permeabilization, petechial hemorrhage and premature ventricular
      contractions (PVCs) have been demonstrated in an in vivo rat model of myocardial
      contrast echocardiography (MCE). The purpose of this study was to compare these
      effects for three US Food and Drug Administration (FDA)-approved ultrasound (US)
      contrast agents (US CA): Optison, Definity and Imagent. Evans blue dye, an
      indicator of microvascular permeability, and a contrast agent were injected IV in
      anesthetized rats suspended in a water bath to mimic scanning depths seen in
      clinical echocardiology. Diagnostic US B-mode scans with 1:4 end-systolic
      triggering were performed at 1.7 MHz using a cardiac phased-array scanhead to
      provide a short axis view of the left ventricle. To elicit readily measurable
      effects for comparisons, relatively high doses of the agent were used (50 to 500
      microL kg(-1) for Optison, 25 to 200 microL kg(-1) for Imagent, 10 to 100 microL
      kg(-1) for Definity). Microvascular leakage was characterized by the area of
      Evans blue dye coloration on the hearts and by extraction of the dye from tissue
      samples. The number of petechia were counted on the epicardial surface of excised
      hearts. PVCs were counted from ECG traces recorded with the MCE images. Neither
      evidence of capillary leakage nor PVCs were seen in sham animals. Based on volume
      dose, Definity MCE produced more microvascular leakage, but there was no apparent
      difference between the three agents' microvascular damage potential, which
      increased linearly with dose at low doses, when expressed in terms of the number
      of stabilized microbubbles. Definity MCE resulted in fewer PVCs than the other
      agents. The effects increased strongly with peak rarefactional pressure
      amplitude, with apparent thresholds for petechiae at 0.4 MPa and for PVCs at
      about 1.0 MPa. These results should be of value for minimizing adverse potential
      in diagnosis and optimizing efficacy in therapeutic applications.

PMID- 14962613
TI  - Possible temperature effects computed for acoustic microscopy used for living
      cells.
AB  - Imaging of living cells or tissues at a microscopic resolution, where GHz
      frequencies are used, provides a foundation for many new biological applications.
      The possible temperature increase causing a destructive influence on the living
      cells should be then avoided. However, there is no information on possible local
      temperature increases at these very high frequencies where, due to strongly
      focused ultrasonic beams, nonlinear propagation effects occur. Acoustic
      parameters of living cells were assumed to be close to those of water; therefore,
      the power density of heat sources in a water medium was determined as a basic
      quantity. Hence, the numerical solution of temperature distributions at the
      frequency of 1 GHz was computed for high and low powers generated by the
      transducer equal to 0.32 W and 0.002 W. In the first case, typical nonlinear
      propagation effects were demonstrated and, in the second one, propagation was
      almost linear. The focal temperature increase obtained in water equaled 14
      degrees C for the highest possible theoretical repetition frequency of fr = 10
      MHz and for the thermal insulation at the sapphire lens-water boundary.
      Simultaneously, the scanning velocity of the tested object was assumed to be
      incomparably low in respect to the acoustic beam velocity. The maximum
      temperature increase in water occurred exactly at this boundary, being equal
      there to 20 degrees C. It was shown that, first of all, the very high absorption
      of water was significant for the temperature distribution in the investigated
      region, suppressing the focal temperature peaks. Because the temperature
      increases are proportional to the repetition frequency, so for example, at its
      practical value of fr = 0.1 MHz, all temperature increases will be 100 times
      lower than listed above. For the low transducer power of 0.002 W, the
      corresponding temperature increases were about 140 times lower than those for the
      high power of 0.32 W. The presented solutions are devoted mainly to the
      reflection pulse mode; however, they can be also applied for the transmitting
      (continuous-wave) mode, as shown in an example. Pressure distributions were
      computed for the acoustic field of the microscope for the first and higher
      harmonics. Hence, at the frequency of 1 GHz, the effective focal radius in water
      measured as the -6-dB amplitude pressure drop was found to be 1,1 microm, and 0.7
      microm for the second harmonic, independently of the assumed transducer power. So
      the width of the beam, scanning the living cells in the focal region, was equal
      to 2.2 microm at the fundamental frequency of 1 GHz.

PMID- 14962614
TI  - Combination of thermal and cavitation effects to generate deep lesions with an
      endocavitary applicator using a plane transducer: ex vivo studies.
AB  - In the high-intensity focused ultrasound (US), or HIFU, field, it is well-known
      that the cavitation effect can be used to induce lesions of larger volume. The
      principle is based on the increase in the equivalent attenuation coefficient of
      the tissue in the presence of the bubbles created by cavitation. The elementary
      lesions produced by combination of cavitation and thermal effects, using focused
      transducers, were spherical and developed upstream of the focal point. This paper
      presents a method that combines cavitation with a thermal effect to obtain deeper
      lesions using a plane transducer, rather than a focused one. The cavitation
      effect was produced by delivering intensities of 60 W/cm2 at the face of the
      transducer for 0.5 s. The applicator was then rotated through 90 degrees at a
      constant speed of between 0.5 and 1.5 degrees /s. During this rotation, ex vivo
      tissues were exposed continuously to an acoustic intensity of 14 W/cm2 to combine
      the cavitation effect with a thermal effect. The necroses were, on average, twice
      as deep when the cavitation effect was used as those obtained with a thermal
      effect alone. Observed macroscopically, the lesions have a very well-delimited
      geometry. Temperature measurements made at different angles of treatment have
      shown that they were coagulation necroses.

PMID- 14962615
TI  - Feasibility of a transurethral ultrasound applicator for coagulation in prostate.
AB  - Transurethral resection of the prostate (TURP) is the surgical method routinely
      used in clinics to treat benign prostate hyperplasia (BPH). The purpose of this
      work is to demonstrate the feasibility of a transurethral ultrasound (US)
      applicator based on a miniature US flat transducer to coagulate prostatic
      tissues. Rabbit liver was found to comply well with human prostate. A significant
      fall in Doppler signal amplitude immediately after treatment demonstrated the
      applicator's ability to achieve haemostasis. The therapeutic depth extended from
      6 to 10 mm, depending on conditions of exposure, and the coagulation rate ranged
      between 51% and 99%. The coagulated zone pinpointed on histological examination
      could be easily correlated to a permanent hypoechoic zone observed on B-scans of
      treated zones. This observation is most likely due to temperature-related changes
      in the acoustic attenuation of liver and, unfortunately, may not be visible in
      the prostate.

PMID- 14962616
TI  - Emboli detection using a new transducer design.
AB  - We have presented, in a previous study, a new approach to detect, characterize
      and estimate the size of gaseous emboli, based on the nonlinear behavior of
      gaseous bubbles. In this study, a specific transducer design has been developed
      to be used for such a purpose. It is composed of two separate transmitting and
      receiving capabilities. The transmit part, consisting of a lead zirconate
      titanate (PZT) material, emits at a frequency of 500 kHz and could generate
      pressures up to 410 kPa. On the top of the transmit surface, a thin
      polyvinylidene difluoride (PVDF) layer is glued and used for receiving
      frequencies from 250 kHz (f0/2) up to 2.5 MHz (5 f0). To evaluate this new
      design, ultrasonic measurements were carried out with gas bubbles with diameters
      ranging from 10 microm up to 90 microm and solid particles between 350 microm and
      550 microm. The experimental results confirmed our previous findings: gaseous
      emboli with a diameter close to the resonance size scatter significantly at
      higher harmonic components (from the second harmonic up to the fifth), and
      bubbles with a diameter around twice the resonance size produce a subharmonic
      and/or an ultraharmonic component. Meanwhile, solid particles and other bubble
      sizes behave only linearly and their scattered spectrum appeared without any
      harmonics. The study demonstrates the utility of this approach in using a single
      transducer to detect and characterize selective gaseous emboli from other
      particles using their nonlinear behavior.

PMID- 14962617
TI  - Accuracy of spectral Doppler flow and tissue velocity measurements in ultrasound
      systems.
AB  - Blood and tissue velocity are measured and analysed in cardiac, vascular and
      other applications of diagnostic ultrasound (US). An error in system calibration
      is a potential risk for misinterpretation of the measurements. To determine the
      accuracy in velocity calibration, we tested three common commercial US systems
      using a Doppler string phantom. We tested pulsed and continuous-wave Doppler
      modes for velocities relevant to both cardiac blood flow and tissue-velocity
      estimation. The US systems were tested with settings and transducers commonly
      used in cardiac applications. One system consistently overestimated velocity by
      about 5%, whereas the other two systems were quite accurate in velocity
      estimation. These findings emphasize the importance of continuous quality control
      of US equipment.

PMID- 14962618
TI  - Sleep researchers need to bring Darwin on board: elucidating functions of sleep
      via adaptedness and natural selection.
AB  - The development of neural multifunctionality - given brain regions carrying out
      more than one function - conferred great efficiency on brain function at early
      stages of evolution. This applied to animals that led relatively simple lives
      with few needs for long-term memories, such as many lower invertebrates - many
      molluscs, echinoderms, worms, etc. As more complex lifestyles and detailed focal
      vision evolved, needs for self-initiated and reflexive activities increased in
      frequency, and recognition of many locales, conspecifics, and other forms of life
      became essential. These developments were accompanied by greatly expanded needs
      for neural processing supporting sensory and motor activities, and establishing
      and storing long-term memories. Since these categories of neural processing occur
      in largely overlapping brain regions, brain functioning would have become
      increasingly maladaptive, had the evolution of these more complex lifestyles not
      been accompanied by compensating adaptations that obviated these potentially
      conflicting brain activities. These adaptations consisted of: first, restful
      waking; second, primitive sleep; and finally, fully developed sleep, with its
      specialized rapid-eye-movement and non-rapid-eye-movement states, that contribute
      to the maintenance of great efficiency of brain function. The only animals with
      detailed focal vision that can achieve highly efficient brain function without
      sleep, are those in which demands on memory processing are greatly reduced in
      consequence of routine, monotonous, almost purely reflexive lifestyles, with few
      needs for acquiring experiential long-term memories. The best known animals in
      this non-sleeping category are tunas and many sharks.

PMID- 14962619
TI  - Daytime parahypnagogia: a state of consciousness that occurs when we almost fall
      asleep.
AB  - Based on a series of self-reports of a previously undescribed and undocumented
      experiential event, we are postulating the existence of a newly identified state
      of consciousness, daytime parahypnagogia (DPH). DPH is more likely to occur when
      one is tired, bored, suffering from attention fatigue, and/or engaged in a
      passive activity. Individuals describe DPH as a transient and fleeting episode
      that is dissociative, trance-like, dreamlike, uncanny, and often pleasurable;
      but, unlike a daydream, it is not self-directed. A DPH episode is spontaneous and
      may consist of a flash image, thought, and/or creative insight that is quickly
      forgotten. However, the individual remains aware of having had a DPH experience.
      This paper details the experiential characteristics associated with DPH. Through
      a brief review of the literature, the authors differentiate DPH from related
      phenomena and establish DPH as a unique and distinct altered state of
      consciousness.

PMID- 14962620
TI  - Biophotons, microtubules and CNS, is our brain a "holographic computer"?
AB  - Several experiments show that there is a cell to cell communication by light in
      different cell types. This article describes theoretical mechanisms and
      subcellular structures that could be involved in this phenomenon. Special
      consideration is given to the nervous system, since it would have excellent
      conditions for such mechanisms. Neurons are large colourless cells with wide
      arborisations, have an active metabolism generating photons, contain little
      pigment, and have a prominent cytoskeleton consisting of hollow microtubules. As
      brain and spinal cord are protected from environmental light by bone and
      connective tissue, the signal to noise ratio should be high for photons as
      signal. Fluorescent and absorbing substances should interfere with such a
      communication system. Of all biogenic amines nature has chosen the ones with the
      strongest fluorescence as neurotransmitters for mood reactions: serotonin,
      dopamine and norepinephrine. If these mechanisms are of relevance our brain would
      have to be looked upon as a "holographic computer".

PMID- 14962621
TI  - Uric acid administration for neuroprotection in patients with acute brain
      ischemia.
AB  - Uric acid is the end product of purine metabolism and a powerful water-soluble
      antioxidant and radical scavenger in humans whose generation is increased in
      situations of oxidative stress, such as brain ischemia. Although hyperuricemia
      has been related to an increased risk of cardiovascular events, the association
      was not found significant in many studies after adjustment for the effect of
      confounders. In the ischemic rat brain, the administration of uric acid results
      in neuroprotection and improved behavioral outcome. The severity of neurological
      impairment and the volume of infarction in patients with stroke have been found
      inversely related to the concentration of uric acid. In healthy volunteers, uric
      acid has been administered without untoward effects to show a conspicuous
      reduction of oxidative stress. We hypothesize that the administration of uric
      acid could be beneficial and cost effective in patients sustaining acute
      oxidative stress, such as those with acute ischemic stroke. Uric acid could also
      extend to more than 3 h the therapeutic window of rt-PA after stroke and it could
      limit the appearance of neurobehavioral changes after cardiopulmonary bypass.
      Prospective double blind randomized controlled trials are needed to test the
      value of uric acid in these clinical settings in which oxyradical formation is
      prominent.

PMID- 14962622
TI  - The two faces of L-DOPA: benefits and adverse side effects in the treatment of
      Encephalitis lethargica, Parkinson's disease, multiple sclerosis and amyotrophic
      lateral sclerosis.
AB  - Parkinson's disease, encephalitis lethargica, multiple sclerosis and amyotrophic
      lateral sclerosis patients all display two distinct types of symptoms. Some of
      these are due directly to a deficiency of dopamine and are quickly reduced by
      laevodihydroxyphenylalanine (L-DOPA). The second set, however, are the result of
      neurological damage caused by metabolites of dopamine, which include dopachrome
      and other chrome indoles that are both hallucinogenic and neurotoxic. If this
      hypothesis is correct, three corollaries follow. Patients of all four disorders
      should display excessive oxidative stress, natural methyl acceptors should delay
      development and elevated antioxidant supplementation, given with L-DOPA, ought to
      prolong the "honeymoon" period in which the benefits of the drug out weigh its
      subsequent disadvantages. A literature review suggests that all three corollaries
      are probably correct.

PMID- 14962623
TI  - Pulse wave encephalopathy: a spectrum hypothesis incorporating Alzheimer's
      disease, vascular dementia and normal pressure hydrocephalus.
AB  - The disorders of Alzheimer's disease, vascular dementia and normal pressure
      hydrocephalus are all causes of dementia in the elderly population. It is often
      the case that it is clinically very difficult to tell these diseases apart. All
      three forms of dementia share the same risk factors, which for the most part are
      vascular risk factors. This paper proposes that there is an underlying vascular
      pathophysiology behind these conditions, which is related to the strength of the
      pulse waves induced in the craniospinal cavity by the arterial vascular tree. It
      is proposed the manifestation of the dementia in any one patient is dependant on
      the way that the pulsations interact with the brain and its venous and
      perivascular drainage. This interaction is predominately dependant on the
      compliance of the craniospinal cavity and the chronicity of the increased pulse
      wave stress.

PMID- 14962624
TI  - The prenatal autistic imprinting hypothesis: developmental maladaptation to the
      environmental changes between womb and the social world.
AB  - Although the importance of biological and genetic aspects of the etiology is well
      recognized, the pathological process of autism still remains to be elucidated. In
      contrast to a qualitative dichotomy concept, a dimensional perspective that
      places the autistic traits as quantitative extremes can easily explain the
      diversity and subtlety of the clinical features. In a dimensional (quantitative
      continuum) condition, no single qualitative process can distinguish the extremes
      from normal variations. In addition, the traditional view, which regards autism
      as a hypo-reproductive disease with a strong genetic contribution, cannot
      interpret the recent worldwide prevalence of autism. From a novel viewpoint, we
      have proposed 'the prenatal autistic imprinting hypothesis' in which autism is
      regarded as an inevitable consequence of human social evolution in both past and
      future. Postulated primary phenotypes are closely associated with the autistic
      savant skills and the autistic adherent temperament, and might increase the
      chance of specific prenatal experiences, named 'autistic imprinting'. An earlier
      prenatal brain growth and an earlier establishment of a type of consciousness may
      be critical for the imprinting process. A postnatal autistic social maladaptation
      may be a mere outcome of the putative intrauterine behavioral adaptation in
      individuals with the primary phenotypes. Both an autistic manner of thinking,
      which is referred to as 'visual thinking', and the prenatal early development of
      visual cortical architectures may play a key role in the autistic imprinting
      process.

PMID- 14962625
TI  - A possible association between fetal/neonatal exposure to radiofrequency
      electromagnetic radiation and the increased incidence of autism spectrum
      disorders (ASD).
AB  - Recently disclosed epidemiological data indicate a dramatic increase in the
      incidence of autism spectrum disorders. Previously, the incidence of autism has
      been reported as 4-5 per 10000 children. The most recent evidence indicates an
      increased incidence of about 1 per 500 children. However, the etiology of autism
      is yet to be determined. The recently disclosed data suggest a possible
      correlation between autism incidence and a previously unconsidered environmental
      toxin. It is generally accepted in the scientific community that radiofrequency
      (RF) radiation is a biologically active substance. It is also readily
      acknowledged that human exposures to RF radiation have become pervasive during
      the past 20 years, whereas such exposures were uncommon prior to that time. It is
      suggested that fetal or neo-natal exposures to RF radiation may be associated
      with an increased incidence of autism.

PMID- 14962626
TI  - Daily hassles, cortisol, and the pathogenesis of depression.
AB  - Daily hassles and/or ongoing stress are associated with increased cortisol
      secretion in healthy individuals. Hassles are also associated with increased
      cortisol levels in depressed patients. Considerable evidence suggests that
      hypercortisolism is involved in the pathogenesis of depressive disorders. Over
      the past decade, there has been a shift from viewing excessive hypothalamic
      pituitary-adrenal (HPA) activity in depression as an epiphenomenon to its having
      specific effects on symptom formation. The author suggests that increased
      cortisol secretion caused by daily hassles and/or ongoing stress contributes to
      the development of depressive disorders. Minor stressful events may lead to
      depression in vulnerable individuals. Genetic factors interact with environmental
      factors to influence the vulnerability to stress and mood disorders. The author
      also proposes that elevated cortisol levels associated with stressful daily
      events may worsen the condition of depressed patients. The author notes that one
      of the goals of prevention of stress-related disorders is to help individuals be
      more competent in managing their behavior and emotions in reaction to negative
      aspects of their environment, and briefly discusses stress management methods and
      techniques. The risk of developing depression is determined by a complex
      interplay between genetic susceptibility, environmental exposures, and aging.
      These influences also account for long term changes in the regulation of HPA
      function. Further studies of HPA function may not only advance our understanding
      of the role of the HPA system in the etiology and pathogenesis of psychiatric
      disorders, but also be useful in refining conceptions of psychiatric disorders
      themselves and possible approaches to the treatment of these conditions.

PMID- 14962627
TI  - Dysautonomia in chronic fatigue syndrome: facts, hypotheses, implications.
AB  - The diagnosis of chronic fatigue syndrome (CFS) is based on patient history and
      treatment on cognitive behavior therapy and graded exercise. There is increasing
      evidence that dysautonomia occurs in CFS manifest primarily as disordered
      regulation of cardiovascular responses to stress. We impart our experience
      relating to diagnosis, monitoring, and treatment of CFS based on identification
      and management of dysautonomia. Recently proposed methods for assessment of the
      cardiovascular reactivity, the 'hemodynamic instability score' (HIS) and the
      'Fractal and Recurrence Analysis-based Score' (FRAS), served for this purpose. On
      HUTT, a particular dysautonomia is revealed in CFS patients that differ from
      dysautonomia in several other disorders. This distinct abnormality in CFS can be
      identified by HIS >-0.98 (sensitivity 84.5% and specificity 85.1%) and FRAS >
      +0.22 (sensitivity 70% and specificity 88%). Therefore, the HIS and FRAS may be
      used, in the appropriate clinical context, to support the diagnosis of CFS, which
      until now, could only be subjectively inferred. A pilot study suggested that
      midodrine treatment, directed at the autonomic nervous system in CFS, results
      first in correction of dysautonomia followed by improvement of fatigue. This
      finding implies that dysautonomia is pivotal in the pathophysiology CFS, at least
      in a large part of the patients, and that manipulating the autonomic nervous
      system may be effective in the treatment of CFS.

PMID- 14962628
TI  - Chaotic solar cycles modulate the incidence and severity of mental illness.
AB  - This paper hypothesizes that the intensity of ultraviolet radiation (UVR) from
      the Sun predisposes humans to polygenic mutation fostering major mental illness
      (MMI) and other disorders of neurodevelopment. In addition, the variation in the
      intensity of this radiation acts to stress immune systems, possibly mediated by
      cytokines, resulting in variable clinical expressions of mental illness and
      autoimmune disorders. Organisms can adapt to chronic high-intensity UVR by
      producing melanin and by retaining various pigments. We found that 28% of 11-year
      solar cycles produce particularly severe solar flares during which UVR is 300%
      more intense and hence more damaging than normal. Out of a total of six severe
      cycles in the past 250 years, four have occurred in the past 55 years, possibly
      explaining the apparent increase in the incidence of MMI in recent decades. UVR
      is 10 times more mutagenic than ionizing radiation to nuclear DNA, and especially
      damaging to mitochondrial DNA. However, variable light as manifested by seasons
      stresses adaptability to UVR, possibly through an immune mechanism. We show that
      the region of the Earth having the most UVR, relative to the most variation in
      that light, is at 54 +/-10 degrees (N or S) latitude. Therefore, the most
      potential damage from sunlight occurs between the Equator and the Poles, not at
      the Equator itself. The human brain, our most important organ of adaptability,
      must be able to survive environmental variation, with successful matching to the
      environment resulting in adaptation. Unsuccessful adaptation to UVR (and possibly
      other types of radiation) results in mutation, which can produce neuro-chemical
      abnormalities manifested by MMI. We postulate that the combination of intensity
      and variation in UVR serves as a global modulator of MMI.

PMID- 14962629
TI  - Down-regulation of the Trk-B signal pathway: the possible pathogenesis of major
      depression.
AB  - Major depressive disorder (MDD) is a common mental disease with unknown etiology.
      Recent studies have suggested that decreased brain-derived neurotrophic factor
      (BDNF) may be implicated in the pathogenesis of MDD. Instead of a decrease in
      central BDNF, however, studies utilizing genetic depression animal models have
      found elevated levels of the factor. In the brain, BDNF exerts its influence
      chiefly by signaling through tyrosine receptor kinase B (Trk-B). In this report,
      it is suggested that Trk-B pathway down-regulation may be the major pathogenesis
      for MDD, while stress, which may reduce central BDNF, acts as a precipitation
      factor to further dampen central BDNF activity and contribute to the development
      of depression. Further, several possible mechanisms of Trk-B pathway down
      regulation, and the implications for this down-regulation in MDD are discussed.

PMID- 14962630
TI  - Did some 18th and 19th century treatments for mental disorders act on the brain?
AB  - Review of 18th and 19th century psychiatric therapies raises the possibility that
      several may have altered the activity of vasopressin or Na-K-ATPase. Bleeding,
      whirling, nausea created by medicines, and vagus nerve stimulation by application
      of electricity through the skin all perturb the hypothalamic hormone, arginine
      vasopressin, while helleborus and digitalis inhibit the sodium pump enzyme, Na-K
      ATPase. These approaches were used with reported benefit many years ago, acting
      on the brain in ways ongoing research suggests may play a role in affective
      disorders. Study of long-abandoned treatments may clarify their mechanisms of
      action and the characteristics of responsive patients.

PMID- 14962631
TI  - Socioeconomic status and health: a neurobiological perspective.
AB  - Socioeconomic status (SES) is one of the strongest predictors of health in
      industrial nations. This is especially true of societies with large disparities
      between rich and poor. Evidence suggests that the interactions between
      individuals of different SES play a crucial role in mediating the effects of SES
      on health. The question is why? Because humans are extremely social animals,
      their sense of well being is to a large extent determined by their social
      interactions. In hierarchical societies, individuals at every level of the
      hierarchy have to submit to those above and the recognition of this
      submissiveness generates emotions such as shame, anger and depression. These
      emotions lead to the activation of physiological alarm systems such as the
      hypothalamic pituitary adrenal axis and the sympathetic nervous system. The
      chronic activation of these systems alter their set points. This results in
      changes in the systems' different target organs responsible for diseases such as
      adult onset diabetes, hypertension, atherosclerosis, major depression and
      autoimmune diseases. Recent evidence from neurobiology show that one brain area,
      the amygdala, plays a pivotal role in processing social emotions. Anatomical and
      physiological studies of the amygdala in animals show how this area could play
      the central role in activating the alarm systems. This recent evidence brings a
      deeper level of plausibility to the postulated mechanisms of activation of the
      alarm systems by social emotions. Other experimental evidence also shed more
      light on the pathways responsible for translating psychosocial experiences into
      physiological perturbations.

PMID- 14962632
TI  - Understanding data in clinical research: a simple graphical display for plotting
      data (up to four independent variables) after binary logistic regression
      analysis.
AB  - In clinical research, suitable visualization techniques of data after statistical
      analysis are crucial for the researches' and physicians' understanding. Common
      statistical techniques to analyze data in clinical research are logistic
      regression models. Among these, the application of binary logistic regression
      analysis (LRA) has greatly increased during past years, due to its diagnostic
      accuracy and because scientists often want to analyze in a dichotomous way
      whether some event will occur or not. Such an analysis lacks a suitable,
      understandable, and widely used graphical display, instead providing an
      understandable logit function based on a linear model for the natural logarithm
      of the odds in favor of the occurrence of the dependent variable, Y. By simple
      exponential transformation, such a logit equation can be transformed into a
      logistic function, resulting in predicted probabilities for the presence of the
      dependent variable, P(Y-1/X). This model can be used to generate a simple
      graphical display for binary LRA. For the case of a single predictor or
      explanatory (independent) variable, X, a plot can be generated with X represented
      by the abscissa (i.e., horizontal axis) and P(Y-1/X) represented by the ordinate
      (i.e., vertical axis). For the case of multiple predictor models, I propose here
      a relief 3D surface graphic in order to plot up to four independent variables
      (two continuous and two discrete). By using this technique, any researcher or
      physician would be able to transform a lesser understandable logit function into
      a figure easier to grasp, thus leading to a better knowledge and interpretation
      of data in clinical research. For this, a sophisticated statistical package is
      not necessary, because the graphical display may be generated by using any 2D or
      3D surface plotter.

PMID- 14962633
TI  - Observations on the proposed relationship between infection burden and early
      malignancy in developing countries (e.g., India).
AB  - Sastry and Parikh [Med. Hypotheses 60(4) (2003) 573] have recently sought an
      explanation for the fact that the occurrence of a particular cancer in
      populations in a developing country such as India takes place at a younger age
      (about one decade) than in populations in Western countries. They have
      hypothesized that a higher infectious burden in India gives rise to repeated cell
      divisions leading to early senescence of immune cells, and, thence their reduced
      ability for immune surveillance against cancer, resulting in earlier onset of
      cancer. The analysis presented here points out to some difficulties with this
      interpretation, both on empirical and theoretical grounds. The reduced
      surveillance ability, caused by higher infectious burden, of the immune cells
      postulated by Sastry and Parikh [loc. cit.] would also mean that populations in
      India should suffer higher incidence of cancer, as compared to people in Western
      countries; the empirical data show that, in fact, quite the opposite is true - in
      the present communication shows that for many common cancers, typical cities in
      India show the lowest incidence. Theoretically, it is postulated here that
      repeated heavy infections in India, in fact, challenge the immune system,
      particularly the adaptive immune system and create an immunological memory: this
      trains and strengthens the immune system against the future battles. Also it is
      shown that the shortening of the telomeric cap by repeated cell divisions caused
      by heavy infectious attacks, as argued by Sastry and Parikh [loc. cit.], is not
      the cause of earlier onset of cancers among Indians; in fact, when telomeric caps
      become shortened to a critical point, a danger signal is generated arresting the
      cell cycle - thus, it provides a fundamental mechanism for ordering the cell to
      cease proliferation. It is suggested that the root of occurrence of cancers at an
      earlier age in India perhaps lies in the accumulation of mutations at an earlier
      age among Indians who do develop cancers; the factors responsible for these
      accelerated mutations are not clear at the present time and need further
      investigation.

PMID- 14962634
TI  - Calculating the etiology of systemic lupus erythematosus.
AB  - Objective was to clarify the etiology and pathogenesis of systemic lupus
      erythematosus (SLE). Drug-induced lupus (DIL) and SLE are both found in humans,
      are exacerbated by the same viruses or drugs, and they are both more common in
      slow acetylators. Thus, DIL can be used as a model for SLE and the Adhami
      equation of DIL can be applied to SLE. Polyamines are the only possible link
      between the viral and amine hypotheses of SLE pathogenesis. Based on the Adhami
      equation, polyamines can explain the actual annual incidence of SLE in the
      general population. Putrescine is a very weak SLE-causing agent, while spermine
      and spermidine contribute equally in triggering SLE. The positively charged
      polyamines bind to negatively charged internucleosomal DNA and change its
      conformation from B (non-immunogenic) to Z (immunogenic). This is the major
      contribution of polyamines in triggering SLE. The other effects of polyamines are
      only secondary. Apoptosis is a necessary step in SLE pathogenesis, because it
      causes the internucleosomal fragmentation of DNA and exposes Z-DNA to the immune
      system (due to cell death). The next step is the production of anti-DNA
      antibodies, followed by other SLE phenomena. Polyamines not only cause SLE, but
      they are also important in sustaining the disease. Other endogenous and exogenous
      amines have additive effects with polyamines and may contribute in exacerbating
      SLE. When SLE is in the active phase, polyamine levels are higher as compared to
      remissions. Fluctuations in polyamine levels due to diet, metabolic factors,
      infections, intestinal flora, etc. or the presence of other amines may explain
      the course of SLE, characterized by remissions and exacerbations. Acetylcysteine
      is a drug that can be completely metabolized to acetyl groups. As such, this drug
      is proposed as the ideal acetyl donor for the acetylation of polyamines and other
      SLE-triggering compounds. Clinical trials will be necessary to test the role of
      acetylcysteine in the etiologic treatment of SLE. CONCLUSIONS: Changes in DNA
      conformation by polyamines are the first step in SLE pathogenesis. Many genetic
      and environmental factors may increase or decrease the effects or levels of
      polyamines, causing SLE exacerbations or remissions. Viruses and other infectious
      agents may cause SLE by producing polyamines or by increasing the levels of
      endogenous polyamines. The major autoimmune diseases are characterized by
      remissions and exacerbations and not by a continuously progressive course, as
      commonly believed. Consequently, they are not sustained by internal vicious
      cycles, but by the initial triggering agent(s). While the conventional treatment
      of autoimmune disorders is important in minimizing tissue damage, the
      neutralization of their etiology may be important in curing and preventing
      autoimmunity.

PMID- 14962635
TI  - How the endothelium and its bone marrow-derived progenitors influence development
      of disease.
AB  - The association between diseases accompanied by abnormal endothelial/vascular
      function (atherosclerosis, hypertension, diabetes mellitus, preeclampsia), and
      conditions characterized by increased tissue growth and normal
      endothelial/vascular function (cancer, placental size, birth length, adult
      height) could be caused by inherited characteristics of endothelial cells and
      their bone marrow-derived precursors. The genotype responsible for normal
      endothelial/precursor function could be modified by intrauterine and postnatal
      endothelial injury; telomere shortening caused by increased endothelial precursor
      proliferation in response to injury can result in premature endothelial
      senescence and a decreased precursor proliferative potential, thereby leading to
      an abnormal endothelial/precursor phenotype and the associated diseases. The
      individual endothelial/precursor phenotype could be established early in life and
      its changes in response to risk factors for diseases followed over time, thus
      providing a unique opportunity for identification and early institution of
      prophylactic and therapeutic interventions in diseases that cause most of the
      morbidity and mortality in advanced industrialized societies.

PMID- 14962636
TI  - Silent myocardial ischemia may be related to inflammatory response.
AB  - Silent myocardial ischemia (SMI) is a common phenomenon in patients with coronary
      artery diseases, which frequently occurs at rest, during daily life activities or
      after physical or emotional exertion. Although individual differences in pain
      threshold may partially explain the variability in pain perception, the
      mechanisms responsible for SMI are not well understood. A defective warning
      mechanism was proposed by some investigators as the reason for the absence of
      pain, stressing that sensibility to pain differs from patient to patient. A
      central nervous system as well as peripheral nerve endings alteration was also
      posited. There is increasing evidence that the development of atherosclerosis is
      associated with inflammation, and increased levels of inflammatory markers have
      been documented in various settings of coronary artery disease. Patients with
      chronic and stable coronary artery disease have clear evidence of a low-grade
      inflammation, which is independent of traditional cardiovascular risk factors. A
      systemic inflammatory response to coronary angioplasty has also been reported
      after balloon angioplasty and after stent implantation. More recently, intriguing
      observations have shown that there is a particular biochemical pattern of
      inflammatory system activation (an increased production of inflammatory
      cytokines) that explains the lack of anginal symptoms in patients with silent
      myocardial ischemia. That is, pain perception may result from microenviromental
      balance between proinflammatory and anti-inflammatory cytokines.

PMID- 14962637
TI  - Cardiac heart disease in the era of sucrose polyester, Helicobacter pylori and
      Chlamydia pneumoniae.
AB  - Recent evidence associates inflammatory mediators with coronary heart disease.
      Elevation of acute-phase reaction (APR) proteins such as serum amyloid A,
      fibrinogen, CRP and haptoglobin in response to Helicobacter pylori (H. pylori)
      infection was shown to initiate gastritis and ischemic heart disease. Positive
      Chlamydia pneumoniae (C. pneumoniae) serology is associated with increased levels
      of inflammatory cytokines and tumor necrosis factor-alpha (TNF-alpha), which
      stimulates endothelial cell activation, procoagulant activity and angiogenesis in
      patients with coronary heart disease. As a final example, interleukin-6 (IL-6)
      has been proposed to mediate cardiovascular disorders. Public awareness of risks
      of excessive body weight and high levels of serum cholesterol propelled the
      development of synthetic dietary components such as sucrose polyester (SPE) to
      substitute for natural lipids. SPE is a synthetic lipid whose physical properties
      are similar to a natural triacylglycerol with a similar assortment of fatty acids
      and is resistant to lipolysis by gastric and pancreatic enzymes. Intake of SPE in
      lieu of natural lipids is expected to decrease absorption of essential fatty
      acids (EFA) and fat-soluble vitamins among other essentials. Deficiency of EFA
      leads to the formation of faulty cellular membranes, which is manifested as skin
      lesions, growth failure, erythrocyte fragility, impairment of fertility and
      uncoupling of oxidation and phosphorylation. Possibilities of absorption of these
      synthetic lipids into the circulation may represent an unexpected health hazard.
      We have shown that subcutaneous (sc) administration to rabbits of a range of
      lipolysis-resistant lipid-like sorbitol, mannitol and arabitol esters of palmitic
      (P) and lauric (L) acids was found to evoke a mild APR, which in humans could
      contribute to CHD incidence. We suggest a reversal in the commonly accepted role
      of SPE as a sequestor of dietary lipid: SPE may be the lipophilic solute
      contained within the dietary lipid solvent micelle. An alternative conclusion
      regarding the biological effects of excessive dose of SPE in human and pig for a
      short time span should be considered.

PMID- 14962638
TI  - The impaired hyperglycemic peak as an additional indicator of Type 2 diabetes
      development is misdetected.
AB  - Because there is not an optimal control for Type 2 diabetes mellitus (DM2), which
      encompasses about 90% of diagnosed diabetic patients, its prevention is key.
      Early detection of DM2 development can be made through impaired fasting glucose
      and/or impaired glucose tolerance diagnosis. However, cases exist when oral
      glucose tolerance test (OGTT) results show an hyperglycemic peak >or =200 mg/dl
      as a unique alteration. This alteration is defined as impaired hyperglycemic peak
      (IHP) and should be considered as an additional early indicator of DM2
      development. Because IHP is commonly misdetected by the standard OGTT, it is
      proposed that this misdetection can be solved using a closer sampled OGTT. The
      objective of this research was to detect IHP on 225 volunteers using a 10 min
      sampled OGTT during 2 h. Results show the existence of IHP in 25 cases, making it
      the most frequent and the less detected OGTT alteration. In eight of these cases,
      IHP could not have been detected using a standard OGTT, because at 30, 60 and 90
      min, plasma glucose concentrations were <200 200 mg/dl, however, at 40, 50, 70,
      and/or 80 min, IHP exists.

PMID- 14962639
TI  - Ascorbic acid, glycation, glycohemoglobin and aging.
AB  - The glycation of proteins alters both their structure and function. These changes
      have been linked to diabetic disorders and aging. The glycation of hemoglobin is
      also used as a diagnostic tool; the extent of glycation being a reflection of
      blood glucose averaged over a two to three month period. Accurate measures of
      average blood sugar (e.g., glycohemoglobin (GHb)) are important in clinical
      management of diabetes, pregnancy, cancer, etc. Ascorbic acid (AA) can react with
      proteins, including hemoglobin, and possibly interfere with GHb measurements.
      Past reports on the impact of AA on in vivo glycation have been equivocal. We
      studied GHb in subjects supplementing up to 20 g AA daily and found that for each
      30 micromol/L increase in plasma AA, GHb was reduced by approximately 0.1. These
      results suggest that high AA intake can depress glycation, reduce GHb and lead to
      a clinically relevant underestimation of average blood sugar. Because AA is the
      most commonly consumed dietary supplement, awareness of an AA-associated bias in
      GHb is imperative. Of even broader significance is the possibility of AA-mediated
      inhibition of glycation in all proteins and the implications for aging. Moreover,
      AA could contribute through several other mechanisms to slowing of human aging
      (e.g., antioxidant properties, acceleration of pentose phosphate pathway,
      replacement of structural proteins).

PMID- 14962640
TI  - Relationship between dietary antioxidants and childhood asthma: more
      epidemiological studies are needed.
AB  - Approximately 15 million Americans including over 5 million children suffer from
      asthma, the most common chronic disease in childhood. The prevalence of pediatric
      asthma has risen sharply over the past four decades, with the sharpest increases
      occurring in children younger than 6 years and in urban, predominantly minority,
      populations. The reasons for this dramatic increase are not yet clear. Recent
      epidemiological studies indicate a higher prevalence of dietary antioxidant
      deficiency among asthmatics patients. However, the results of these studies are
      inconsistent or even contradictory. Epidemiological studies with robust design
      and use of novel epidemiological tools are urgently needed to examine the impact
      of dietary antioxidants on the incidence of asthma in preschool children. An
      incidence density case-control study which includes non-atopic controls, who are
      matched for age, gender, race, study center and sampling time to each asthmatic
      case will offer a robust study design. A validated food frequency questionnaire
      and an asthma and atopy severity score can be used to interview the parents of
      the recruited children. Risk set sampling may enable us to explore possible
      associations between the type and quantity of dietary antioxidants and the
      development and severity of asthma in such an epidemiological study.

PMID- 14962641
TI  - Too much short chain fatty acids cause neonatal necrotizing enterocolitis.
AB  - Nenatal necrotizing enterocolitis (NEC) is a disease mainly affects premature
      infants. It is well known that prematurity, enteral formula feeding, and
      bacterial colonization are three major risk factors for NEC. Acetic acid,
      propionic acid and butyric acid are short chain fatty acids (SCFAs), which are
      produced mainly in the colon by bacterial fermentation of undigested
      carbohydrates. Although luminal production of modest quantities of SCFAs is
      essential for normal colonic mucosal function, excessive production/accumulation
      of SCFAs may arise in premature infants due to increased luminal carbohydrates
      malabsorption and poor gastrointestinal motility, and may have deleterious
      effects on mucosal integrity. Therefore, it is proposed that too much luminal
      short chain fatty acids cause neonatal NEC.

PMID- 14962642
TI  - The swelling of mitochondria from nitrogen gas; a possible cause of reperfusion
      damage.
AB  - Electron photomicrograph evidence is presented which suggests that the in vivo
      swelling of mitochondria may result from the uptake of nitrogen gas bubbles which
      coalesce to fill the intramitochondrial space during tissue anoxia. These
      observations have led to the hypothesis that nitrogen-filled mitochondria are
      unable to take up oxygen resulting in cell death. A test of this hypothesis also
      represents a probable treatment for stroke, namely the total body washout of
      nitrogen. This can be achieved by the inhalation of an oxygen-helium mixture with
      exhaled gases shunted to ambient atmosphere. This washout should facilitate
      nitrogen egress from the interior of affected mitochondria, allow oxygen uptake
      and a resumption of oxidative metabolism. This hypothesis generally fits well
      with the literature on luxury perfusion following stroke. In cases of luxury
      perfusion the venous blood exiting the lesion is red indicating a decreased
      transfer of oxygen to the extracellular and cytosolic fluids. However, whereas
      luxury perfusion assumes blood flow adequate for delivery of oxygen to the
      tissues, this hypothesis interjects a blockade at the level of oxygen uptake into
      mitochondria, and unless this blockade is reversed it will lead to cell death and
      brain tissue necrosis in the affected regions.

PMID- 14962643
TI  - Bupropion for Blau syndrome.
AB  - Blau syndrome (BS) is an autosomal dominantly inherited disease characterized by
      granulomas and arthritis. The gene mutated in BS was recently found to be CARD15.
      Mutations in this gene also occur in about 20% of patients with Crohn's disease
      (CD), though with different mutations than in the Crohn's patients. We are not
      aware of any cure or specific treatment for BS. We have found that bupropion is
      effective for CD, and we now suggest that bupropion be considered for treatment
      of BS.

PMID- 14962644
TI  - Neo-Lamarckian medicine.
AB  - Darwinian medicine is the treatment of disease based on evolution. The underlying
      assumption of Darwinian medicine is that traits are coded by genes, which are
      often assumed to be sequences of DNA nucleotides. The quantitative genetic
      ramification of this perspective is that traits, including disease
      susceptibility, are either caused by genes or by the environment, with genotype
      by-environment interactions usually considered statistical artefacts. I emphasize
      also examining those epigenetic signals that can be altered by environmental
      perturbations and then transmitted to subsequent generations. Although seldom
      studied, environmentally-alterable meiotically-heritable epigenetic signals exist
      and provide a mechanism underlying genotype-by-environment interactions.
      Environment of a parent can affect its descendants by heritably altering
      epigenetic signals. Neo-Lamarckian medicine is the application of these
      evolutionary epigenetic notions to diseases and could have enormous public health
      and environmental policy implications. If industrial contaminants adversely
      affect organisms by meiotically-heritably altering their epigenetic signals, then
      cleaning up these contaminants will not remedy the problem. Once contaminants
      have adversely altered an individual's epigenetic signals, this harm will be
      transmitted to future generations even if they are not exposed to the
      contaminant. Exposure to environmental shocks such as free radicals or other
      carcinogens can alter cytosine methylation patterns on regulatory genes. This can
      cause cancer by up-regulating genes for cell division or by down-regulating
      tumour suppressor genes. Environmentally-alterable meiotically-heritable
      epigenetic signals could also underlie other diseases, such as diabetes, Prader
      Willi syndrome, and many complex diseases. If environmentally-altered meiotically
      heritable epigenetic effects are widespread - which is an important open
      empirical question - they have the potential to alter paradigmatic views of
      evolutionary medicine and the putative dichotomy of nature versus nurture. Neo
      Lamarckian medicine would thereby shift emphasis from cure to prevention of
      diseases.

PMID- 14962645
TI  - Aging as an evolved characteristic - Weismann's theory reconsidered.
AB  - Theories of aging have become significantly more important because of discoveries
      which indicate that aging is not universal or inevitable and which therefore
      indicate that major medical intervention in aging is possible. Directions of anti
      aging research could be significantly influenced by basic theories of aging.
      Weismann proposed in 1882 that aging was an evolved genetically programmed
      adaptation that had a species benefit. Since then this idea has been largely
      replaced by various theories in which aging is not an adaptation but results from
      accumulated adverse mutations or is an adverse side effect of some essential
      process. Arguments are presented to the effect that aging is an evolved
      beneficial characteristic and is therefore likely to result from a more complex
      and structured mechanism than if it resulted from more random processes such as
      mutation accumulation. Further, aging appears to be one of a number of related
      and interactive life-cycle characteristics including age-at-puberty suggesting
      that it might be controlled by similar biological mechanisms.

PMID- 14962646
TI  - The common variants/multiple disease hypothesis of common complex genetic
      disorders.
AB  - Unlike simple rare Mendelian disorders, the genetic basis for common disorders is
      unclear. A general model of the genetics of common complex disorders is proposed
      which emphasizes the shared nature of common alleles in related common disorders,
      such as schizophrenia and bipolar disorder, Type II diabetes and obesity, and
      among autoimmune diseases. This model, the common variants/multiple disease
      hypothesis, emphasizes that many disease genes may not be disease specific.
      Common deleterious alleles, found at a relatively high frequency in the
      population may play a role in related clinical phenotypes in the context of
      different genetic backgrounds and under different environmental conditions.

PMID- 14962647
TI  - Appearance of leukoaraiosis may be attenuated with compression by a chronic
      subdural hematoma.
AB  - INTRODUCTION/OBJECTIVE: Various pathological changes have been attributed to
      leukoaraiosis. Some investigators have suggested that increase in interstitial
      water may partly contribute to leukoaraiosis. We hypothesized that leukoaraiosis
      may be attenuated by compression to the cerebral hemisphere if interstitial water
      may partly contribute to leukoaraiosis. We retrospectively reviewed patients with
      unilateral chronic subdural hematomas (CSDHs) to investigate the difference in
      appearance of leukoaraiosis between both cerebral hemispheres. METHODS AND
      MATERIAL: Leukoaraiosis on T2-weighted magnetic resonance (MR) images at the
      levels of the centrum semiovale and those of the frontal horns of both cerebral
      hemispheres in five contiguous patients with unilateral CSDHs were scored. The
      difference in the leukoaraiosis scores on the ipsilateral side and contralateral
      side of the CSDH was analyzed. RESULTS: Leukoaraiosis was less prominent on the
      ipsilateral side of the CSDHs than on the contralateral side of the CSDHs, both
      at the level of the centrum semiovale (P=0.02) and that of the frontal horns
      (P=0.03). DISCUSSION AND CONCLUSION: Our results support the theories that
      interstitial water may partly contribute to the appearance of leukoaraiosis on MR
      images.

PMID- 14962648
TI  - Bilateral Wallerian degeneration of the medial cerebellar peduncles after ponto
      mesencephalic infarction.
AB  - Three patients with acute large paramedian ponto-mesencephalic infarctions
      developed a bilateral retrograde degeneration of the medial cerebellar peduncles
      within 4 months after the insult. In an initial magnetic resonance imaging (MRI)
      within the first 2 weeks, the medial cerebellar peduncles showed normal
      intensities, but a control MRI after 4 months showed bright hyperintensities in
      the T2-TSE weighted images, and moderately increased signal intensities in echo
      planar imaging-diffusion weighted imaging were seen, possibly representing
      bilateral Wallerian degeneration of the cerebellar-pontine fibers.

PMID- 14962649
TI  - MRI and CT findings of neurohypophyseal germinoma.
AB  - OBJECTIVE: Magnetic resonance (MR) imaging and computed tomography (CT) findings
      of neurohypophyseal germinoma have not previously been described in detail. The
      purpose of the present study was to establish the spectrum of MR imaging and CT
      findings in neurohypophyseal germinomas. MATERIALS AND METHODS: MR and CT images
      of 13 consecutive patients (seven males, six females; mean age: 15 years; range:
      6-31 years) with neurohypophyseal germinoma were retrospectively analyzed. The
      diagnosis had been made either histologically (n=8) or clinically according to
      established criteria (n=5). All patients had been examined using MR imaging and
      CT before treatment. RESULTS: On MR imaging, infundibular thickening (up to 16
      mm) was observed in all 13 cases. Hyperintensity of the posterior pituitary on T1
      weighted image was absent in all 13 cases (100%) and 12 of the 13 displayed
      central diabetes insipidus. Ten germinomas (77%) were isointense to cerebral
      cortex on T1-weighted image, but variable intensities were exhibited on T2
      weighted image. MR images revealed intratumoral cysts in six cases (46%), most of
      which demonstrated intra-third ventricular extension. Eleven of the 13 cases
      (85%) revealed hyperdense solid components on unenhanced CT. Calcification was
      absent in all cases (100%). CONCLUSION: Infundibular thickening, absence of the
      posterior pituitary high signal on T1-weighted image, lack of calcification and
      hyperdensity on unenhanced CT are common imaging features of neurohypophyseal
      germinoma.

PMID- 14962650
TI  - CT angiography with three-dimensional techniques for the early diagnosis of
      intracranial aneurysms. Comparison with intra-arterial DSA and the surgical
      findings.
AB  - INTRODUCTION: Cerebral CT angiography (CTA) is an established method applied to
      both the detection and treatment planning of intracranial aneurysms. The aim of
      our study was to compare CTA and digital subtraction angiography (DSA) findings
      with the surgical results mainly in patients with acute SAH and to evaluate the
      clinical usefulness of CTA. MATERIALS AND METHODS: During the last 2 years, 82
      consecutive patients were admitted under clinical symptoms and signs suggestive
      of harboring an intracranial aneurysm. CT angiography performed immediately
      afterwards the plain CT, while DSA was performed within the first 48 h of
      admission. All aneurysms detected were confirmed during surgery or endovascular
      embolization. Repeat DSA was performed in all patients having both the initial
      CTA and the DSA 15 days after the onset of symptoms negative. CT angiograms and
      conventional angiographies were studied by a consensus of two radiologists for
      each technique, who performed aneurysm detection, morphological features
      characterization and evaluation of the technique. RESULTS: Surgical or/and
      endovascular treatment was performed in 45 patients and 53 aneurysms were
      confirmed. Using 3D-CT angiography, we detected 47 aneurysms in 42 patients.
      Conventional angiography depicted 43 aneurysms in 39 patients. The sensitivity of
      CTA for the detection of all aneurysms versus surgery was 88.7%, the specificity
      100%, the positive predictive value (PPV) 100%, the negative predictive value
      (NPV) 80.7% and the accuracy 92.3%. Accordingly, the sensitivity of DSA was
      87.8%, the specificity 98%, the PPV 97.7%, the NPV 89.1% and the accuracy 92.9%.
      Considering aneurysms > or =3 mm, CTA showed a sensitivity ranging from 93.3 to
      100%, equal to that of DSA. CONCLUSION: Cerebral CT angiography has an equal
      sensitivity to DSA in the detection of intracranial aneurysms >3 mm. It has also
      100% detection rate in AcoA and MCA bifurcation aneurysms, while some locations,
      like posterior communicating artery aneurysms, remain problematic. The
      delineating features of each aneurysm are better depicted with CTA due to 3D
      visualization. The use of digital subtraction angiography as a diagnostic tool
      can be limited in equivocal cases.

PMID- 14962651
TI  - Brain MR spectroscopy in children with a history of rheumatic fever with a
      special emphasis on neuropsychiatric complications.
AB  - PURPOSE: To investigate whether there are metabolite changes in basal ganglia of
      children with complete healing of rheumatic fever (RF), history of Syndenham
      chorea (SC) and obsessive compulsive-tic disorder (OCTD) developed after RF when
      compared with healthy controls and each other. MATERIAL AND METHODS: A total of
      49 children with history of RF and 31 healthy controls were included into the
      study. All patients and control group underwent a detailed neuropsychiatric
      evaluation. Children with the history of RF were classified into three groups as;
      group 1: with history of RF without neuropsychiatric complications (NCRF), group
      2: only with history of SC (HSC), group 3: with HSC and OCTD (OCTD). After MR
      imaging, single voxel MR spectroscopy was performed in all subjects. Voxels (15 x
      15 x 15 mm) were placed in basal ganglia. N-acetyl aspartate (NAA)/creatin (Cr),
      and choline (Cho)/Cr ratios were calculated. RESULTS: OCTD were detected in 13
      children with HSC. NAA/Cr ratio was found to be decreased in these children when
      compared with NCRF (n:29), HSC without OCTD (n:7) and control groups (n:31). No
      significant difference was found in metabolite ratios of children with HSC
      without OCTD when compared with NCRF and control groups. There were no
      significant differences in Cho/Cr ratio between patient and control groups.
      CONCLUSION: Although MR imaging findings was normal, MR spectroscopy findings
      (decreased NAA/Cr ratio) in our study support the neuronal loss in basal ganglia
      of children with OCTD and could indicate the development of permanent damage.

PMID- 14962652
TI  - Pigmented villonodular synovitis of the temporomandibular joint: MR findings in
      four cases.
AB  - OBJECTIVE: Although it is a rare condition, pigmented villonodular synovitis
      (PVNS) may involve temporomandibular joint (TMJ). The purpose of this study was
      to describe magnetic resonance (MR) findings of PVNS of the TMJ. METHODS AND
      MATERIAL: Between April 1992 and August 2000, four patients (two men and two
      women, 22-58-year-old) who had histologically proven diagnoses of PVNS in their
      TMJ were found in our institution. Their MR findings were reviewed
      retrospectively, and were correlated with pathologic findings. RESULTS: In all
      four patients, MR images invariably showed profound hypointensity on both T1- and
      T2-weighted sequences. This finding was seen diffusely and homogeneously
      throughout the lesion, and was considered to be due to paramagnetic effect
      attributed to heavy hemosiderin pigmentation, which was revealed by
      histopathological examination. MR images also showed aggressive nature of the
      lesions with adjacent skull base destruction and intracranial extension in two of
      them. CONCLUSION: As is the case in the other anatomic site, PVNS of the TMJ can
      be confidently diagnosed on MR imaging on the basis of the presence of
      hemosiderin. MR imaging also plays a pivotal role in surgical planning by precise
      and detailed localization of the lesion.

PMID- 14962653
TI  - Serial chest CT findings in interstitial lung disease associated with
      polymyositis-dermatomyositis.
AB  - OBJECTIVE: A retrospective study was carried out in two institutions to determine
      serial changes in the pattern, distribution, and extent of interstitial lung
      disease (ILD) associated with polymyositis (PM)-dermatomyositis (DM) using HRCT.
      SUBJECTS AND METHODS: Twenty patients with PM-DM and clinical suspicion of ILD
      who underwent at least two serial HRCT examinations were retrospectively
      evaluated by two readers. Patients were classified according to the dominant CT
      pattern which was correlated with clinical evolution and underlying histology
      when available (n=6). RESULTS: Patients were classified into four groups
      according to the dominant pattern: ground-glass attenuation and reticulation
      (group 1, n=9); honeycombing (group 2, n=4); airspace consolidation (group 3,
      n=4), and normal or almost normal lung (group 4, n=3). Under medical treatment,
      serial HRCT showed that the extent of areas of ground-glass opacities (group 1)
      decreased in five patients, stabilized in two, and increased in two. Pathologic
      findings demonstrated usual interstitial pneumonia (UIP) in two cases and
      unspecified interstitial pneumonia in one. In group 2, extent of honeycombing
      increased in three cases and stabilized in one. In group 3, dramatic resolution
      of airspace consolidation occurred in three cases. Clinical deterioration with
      extensive consolidation at CT and diffuse alveolar damage (DAD) at histology
      occurred in one patient of each of the three previous groups. Lesions stayed
      invisible or progressed slightly in the fourth group. CONCLUSION: In ILD
      associated with PM-DM, clinical deterioration and DAD in the follow-up can be
      observed whatever the HRCT pattern. However, unfavorable evolution is constant
      when honeycombing is present at the initial CT.

PMID- 14962654
TI  - HRCT evaluation of the accessory fissures of the lung.
AB  - INTRODUCTION: The purpose of this study was to classify the accessory fissures of
      the lung and to assess their frequency by using high-resolution CT. METHODS AND
      PATIENTS: HRCT scans of 115 patients were prospectively reviewed. 1 mm thin
      sections were obtained at 10 mm intervals with a scan time of 1.9 s. The fissure
      and its relationship to the segmental bronchovascular structures were then
      evaluated on transverse sections. RESULTS: Forty-four accessory fissures were
      detected in 35 of 115 patients. The most common accessory fissure was the
      inferior accessory fissure (12%). The second most common accessory fissure was
      the left minor fissure (8%). The right superior accessory fissure (5%), the
      accessory fissure between the medial and lateral segments of the right middle
      lobe (5%), and the accessory fissure between the superior and inferior segments
      of the lingula (5%) were seen in equal frequencies. Also, intersegmental
      accessory fissures, namely the fissure between the anterobasal and laterobasal of
      both the right (1%) and the left (2%) lower lobes were detected. We found only
      one subsegmental accessory fissure. DISCUSSION AND CONCLUSION: The inferior
      accessory fissure and the left minor fissure were the most common accessory
      fissures in our study.

PMID- 14962655
TI  - Ancillary lung parenchymal findings at spiral CT scanning in pulmonary embolism.
      Relationship to chest sonography.
AB  - INTRODUCTION/OBJECTIVE: The aim of the study was to compare findings of
      transthoracic sonography (TS) and of spiral computed tomography (sCT) in patients
      with suspected pulmonary embolism (PE). METHODS AND PATIENTS: Peripheral
      parenchymal and pleural findings of TS and sCT were compared in 62 patients (25
      females, 37 males; mean age 62.2 years) with suspected PE. RESULTS: In 39
      patients PE was established, of whose pleura-based lesions could be detected by
      TS in 30 patients and by sCT in 31 patients. Whilst in three of the patients
      parenchymal lesions were exclusively detected by sonography, no peripheral
      abnormalities could be discovered with either technique in five patients. Among
      the nine patients lacking peripheral abnormalities on sonography, four revealed
      peripheral lesions in sCT. In 23 patients without PE, peripheral consolidations
      at CT were detected in six patients whereas two showed lesions on TS. With
      respect to the appearance, pleura-based wedge-shaped consolidations were the main
      parenchymal alterations (82.4% at TS, 66.1% at sCT) as compared with non-wedge
      shaped consolidations (17.6% at TS, 33.9% at sCT). Peripheral lesions were
      located preferentially within the lower lobes. In addition, both localised and
      basal pleural effusion associated with PE could be demonstrated in 58.9% at TS
      and in 23.1% by sCT. DISCUSSIONS AND CONCLUSION: The study shows that in PE
      parenchymal and pleural changes are detectable by TS and sCT. If parenchymal
      findings are present at sCT, peripheral PE should be considered, even in the
      absence of directly visible emboli.

PMID- 14962656
TI  - Does intravenous glucagon improve common bile duct visualisation during magnetic
      resonance cholangiopancreatography? Results in 42 patients.
AB  - INTRODUCTION: Magnetic resonance cholangiopancreatography (MRCP) has been
      demonstrated as a reliable, non-invasive means of biliary tract imaging among
      patients with suspected choledocholithiasis. The aim of this study was to
      establish the impact of intravenous glucagon administration (IVGA) upon
      visualisation of the common bile duct (CBD) and ampulla of Vater during MRCP.
      MATERIALS AND METHODS: Forty-two consecutive, non-diabetic subjects with a
      working diagnosis of symptomatic choledocholithiasis were scanned, pre- and post
      IVGA using the half-Fourier, single shot, turbo-spin-echo (HASTE) sequence.
      Maximum intensity projections (optimised for the extra-hepatic biliary tree and
      ampulla of Vater) were reviewed blindly by three consultant radiologists. The CBD
      images were graded (0-3) according to the length of duct seen. The ampullary
      images were graded according to whether to it was visualised clearly (1), or not
      (0). RESULTS: Following IVGA the CBD was visualised at grade 3 (75-100% of length
      seen) in 14 additional patients compared with images prior to IVGA. Furthermore,
      ampullary visualisation was considered diagnostic in 18 additional patients post
      IVGA. No glucagon-associated adverse effects were observed. CONCLUSION: These
      results demonstrate that IVGA improved visualisation of the CBD and ampulla of
      Vater during magnetic resonance cholangiopanctreatography. This may reduce the
      requirement for repeat investigation or recourse to invasive diagnostic
      procedures (e.g. endoscopic retrograde cholangiopancreatography (ERCP)).

PMID- 14962657
TI  - Lower prevalence of non-tumoral perfusion defects in left hepatic lobe during CT
      arterial portography with splenic artery injection.
AB  - OBJECTIVE: To determine whether there is a difference in the prevalence of non
      tumoral perfusion defects (NTPD) in left hepatic lobe during CT arterial
      portography (CTAP) through splenic (SA) and superior mesenteric artery (SMA)
      injection. METHODS AND PATIENTS: For the preoperative evaluation, 59 patients (20
      females, 39 males) who either have colorectal carcinoma metastasis (n: 42) or
      hepatocellular carcinoma (n: 17) underwent CTAP examination. Patients were
      divided into two groups (SA and SMA) according to the injection artery. The
      presence and type of NTPD in the left hepatic lobe were determined and compared.
      RESULTS: There were significant differences in peripherally located wedge shaped,
      perihilar-periligamentous and pericholecystic NTPD, but no significant difference
      was found in lobar/segmental defects between the groups. CONCLUSIONS: Our study
      demonstrated lower prevalence of NTPD in the left hepatic lobe in CTAPs performed
      through SA injection and we think that this could be explained by the
      streamlining of portal blood flow.

PMID- 14962658
TI  - Partial splenic embolization in patients with idiopathic portal hypertension.
AB  - PURPOSE: To evaluate the effectiveness of partial splenic embolization (PSE) in
      patients with idiopathic portal hypertension (IPH) in reducing variceal bleeding
      episodes, splenomegaly and thrombocytopenia. MATERIALS AND METHODS: Six patients
      (2M, 4F, mean age 30.3 years) with IPH presenting with splenomegaly,
      thrombocytopenia and recurrent variceal bleeding were treated with PSE using
      gelatin sponge (four patients) or Contour particles (two patients) as
      embolization material. RESULTS: PSE was performed successfully in all cases; 3F
      coaxial microcatheters were necessary in two patients due to extreme splenic
      artery tortuosity. The average amount of devascularized parenchyma at CT 1 week
      after PSE was 71%. Splenomegaly and thrombocytopenia improved in all cases, with
      a mean platelet count increase of 120,000/mm(3) and an average 68% reduction of
      spleen volume at follow up. Variceal bleeding did not recur after PSE. Esophageal
      or gastroesophageal varices disappeared (one patient) or significantly reduced
      (five patients) at endoscopic controls. No significant complications were noted.
      The follow up was of at least 18 months in all patients; mean follow up was 28.2
      months. CONCLUSION: In patients with IPH PSE can be effective in preventing
      variceal bleedings, in reducing spleen volume and in significantly increasing
      platelet count; therapeutic results were durable in our population.

PMID- 14962659
TI  - The comparative study of tumor angiogenesis and CT enhancement in pancreatic
      carcinoma.
AB  - PURPOSE: The purpose of this work was to study the correlation of pancreatic
      phase Computed tomography (CT) enhancement, intratumoral microvessel density
      (MVD) and pathologic grades in pancreatic carcinoma and to evaluate the
      relationship between CT enhancement degree and the malignancy degree of
      pancreatic carcinoma. METHODS: 34 patients with pancreatic carcinoma underwent CT
      scanning before resection. The enhancement degrees and forms of tumor were
      observed in pancreatic phase. The operational sample was stained with HE and CD34
      marked by immunohistochemistry. MVD and histopathological grades of pancreatic
      carcinoma were examined. CT enhancement of the tumor, MVD counting in hot spot
      areas of neoplastic parenchymal cells and pathological grades of pancreatic
      carcinoma were comparatively analyzed. RESULT: Highly differentiated pancreatic
      adenocarcinoma was identified in 16 patients, moderately differentiated tumor in
      seven and poorly differentiated tumor in 11. Isodensity CT enhancement was
      demonstrated in 13 cases, slight low density enhancement in nine, slight low
      density enhancement along with small cyst lesion in nine and slight low density
      enhancement along with large cyst lesion in three. The counting of MVD with CD34
      marked by immunohistochemistry in hot spot areas of neoplastic parenchyma cells
      were small in ten cases, medium in 16 and large in eight. The pathological grades
      correlated with CT enhancement of tumor (r=0.7857, P<0.001). The pathological
      grade correlated with MVD counting of tumor (r=0.3613, P<0.05). The CT
      enhancement of tumor correlated with MVD (r=0.6768, P<0.001). CONCLUSION: There
      was obvious and significant correlation between CT enhancement, pathological
      grades and MVD numbers in the hot spot areas of tumor. The extent of CT
      enhancement was inversely proportional to the malignancy degree of pancreatic
      carcinoma, and inversely proportional to MVD numbers in the hot spot areas of
      neoplastic parenchyma. The MVD in the hot spot areas of neoplastic parenchyma
      cells could also reflect the prognosis of the patients, and was directly
      proportional to malignancy degree of pancreatic carcinoma.

PMID- 14962660
TI  - Retrieval of intravascular foreign bodies with goose neck snare.
AB  - PURPOSE: to evaluate the efficacy and advantages of the snare systems in the
      retrieval of foreign bodies from vascular system. MATERIALS AND METHODS: the
      snare technique has been used for intravascular foreign body retrieval. We
      performed percutaneous extraction of intravascular foreign bodies using
      combination multipurpose catheters and a nitinol snare loop. In this report, we
      evaluated the patients who had performed endovascular device reposition or
      foreign body retrieval from 1998 to 2001. RESULTS: foreign body retrieval was
      performed in 15 patients. The foreign bodies consisted of seven fractured port
      catheters, one sheath fragment, one embolization coil, four wire fragments, one
      pace-maker transducer and one dislocated endovascular stent. In no case were
      surgical procedures required, and no complications were encountered. CONCLUSION:
      the snare technique is a useful and a safe method as an alternative procedure to
      surgery. This technique is highly effective with low rate complications.

PMID- 14962661
TI  - ENCODE and ChIP-chip in the genome era.

PMID- 14962662
TI  - The canine olfactory subgenome.
AB  - We identified 971 olfactory receptor (OR) genes in the dog genome, estimated to
      constitute approximately 80% of the canine OR repertoire. This was achieved by
      directed genomic DNA cloning of olfactory sequence tags as well as by mining the
      Celera canine genome sequences. The dog OR subgenome is estimated to have 12%
      pseudogenes, suggesting a functional repertoire similar to that of mouse and
      considerably larger than for humans. No novel OR families were discovered, but as
      many as 34 gene subfamilies were unique to the dog. "Fish-like" Class I ancient
      ORs constituted 18% of the repertoire, significantly more than in human and
      mouse. A set of 122 dog-human-mouse ortholog triplets was identified, with a
      relatively high fraction of Class I ORs. The elucidation of a large portion of
      the canine olfactory receptor gene superfamily, with some dog-specific
      attributes, may help us understand the unique chemosensory capacities of this
      species.

PMID- 14962663
TI  - Expansion of GAA triplet repeats in the human genome: unique origin of the FRDA
      mutation at the center of an Alu.
AB  - Friedreich ataxia is caused by expansion of a GAA triplet repeat (GAA-TR) in the
      FRDA gene. Normal alleles contain <30 triplets, and disease-causing expansions
      (66-1700 triplets) arise via hyperexpansion of premutations (30-65 triplets). To
      gain insight into GAA-TR instability we analyzed all triplet repeats in the human
      genome. We identified 988 (GAA)(8+) repeats, 291 with >or=20 triplets, including
      29 potential premutations (30-62 triplets). Most other triplet repeats were
      restricted to <20 triplets. We estimated the expected frequency of (GAA)(6+)
      repeats to be negligible, further indicating that GAA-TRs have undergone
      significant expansion. Eighty-nine percent of (GAA)(8+) sequences map within G/A
      islands, and 58% map within the poly(A) tails of Alu elements. Only two other
      (GAA)(8+) sequences shared the central Alu location seen at the FRDA locus. One
      showed allelic variation, including expansions analogous to short Friedreich
      ataxia mutations. Our data demonstrate that GAA-TRs have expanded throughout
      primate evolution with the generation of potential premutation alleles at
      multiple loci.

PMID- 14962664
TI  - Isochore structures in the mouse genome.
AB  - The distribution of the G+C content in the mouse genome has been studied using a
      windowless technique. We have found that: (i). Abrupt variations of the G+C
      content from a GC-rich region to a GC-poor region, and vice versa, occur
      frequently at some sites along the sequence of the mouse genome. (ii). Long
      domains with relatively homogeneous G+C content (isochores) exist, which usually
      have sharp boundaries. Consequently, 28 isochores longer than 1 Mb have been
      identified in the mouse genome. A homogeneity index was used to quantify the
      variations of the G+C content within isochores. The precise boundaries, sizes,
      and G+C contents of these isochores have been determined. The windowless
      technique for the G+C content computation was also used to analyze the DNA
      sequence containing the mouse MHC region, which has a GC-poor isochore. This
      isochore is located at the central part of the sequence with boundaries at 468459
      and 812716 bp, where the sequence is extended from the centromeric end to the
      telomeric end. In addition, the analysis of a segment of the rat genome shows
      that the rat genome also has clear isochore structures.

PMID- 14962665
TI  - Comparative sequence analysis of imprinted genes between human and mouse to
      reveal imprinting signatures.
AB  - We performed a comparative genomic sequence analysis between human and mouse for
      24 imprinted genes on human chromosomes 1, 6, 7, 11, 13, 14, 15, 18, 19, and 20.
      The MEME program was used to search for motifs within conserved sequences among
      the imprinted genes and we then used the MAST program to analyze for the presence
      or absence of motifs in the imprinted genes and 128 nonimprinted genes. Our
      analysis identified 15 motifs that were significantly enriched in the imprinted
      genes. We generated a logistic regression model by combining multiple motifs as
      input variables and the 24 imprinted genes and the 128 nonimprinted genes as a
      training set. The accuracy, sensitivity, and specificity of our model were 98,
      92, and 99%, respectively. The model was further validated by an open test on 12
      additional imprinted genes. The motifs identified in this study are novel
      imprinting signatures, which should improve our understanding of genomic
      imprinting and the role of genomic imprinting in human diseases.

PMID- 14962666
TI  - Imprinting analysis of 10 genes and/or transcripts in a 1.5-Mb MEST-flanking
      region at human chromosome 7q32.
AB  - MEST is one of the imprinted genes in human. With the assistance of our
      integration map and the complete sequence in the registry, we mapped a total of
      16 genes/transcripts at the 1.5-Mb MEST-flanking region at 7q32. This region has
      been suggested to form an imprinted gene cluster, because MEST and its three
      flanking genes/transcripts (MESTIT1, CPA4, and COPG2IT1) were reported to be
      imprinted, although two (TSGA14 and COPG2) were shown to escape imprinting. In
      this study, 10 other genes/transcripts were examined for their imprinting status
      in human fetal tissues. The results indicated that 8 genes/transcripts (NRF1,
      UBE2H, HSPC216, KIAA0265, FLJ14803, CPA2, CPA1, and DKFZp667F0312) were expressed
      biallelically. The imprinting status of two (TSGA13 and CPA5) was not conclusive,
      because of their weak and/or tissue-specific expression and inconstant results.
      These findings provided evidence that only 4 of the 16 genes/transcripts located
      to the region show monoallelic expression, while others are not involved in
      imprinting. Therefore, it is less likely that the MEST-flanking 7q32 region forms
      a large imprinted domain.

PMID- 14962667
TI  - Complex organization and structure of sense and antisense transcripts expressed
      from the DIO3 gene imprinted locus.
AB  - The human DIO3 gene and its mouse homolog, Dio3, map to chromosomes 14q32 and
      12F1, respectively, and code for the type 3 deiodinase, an enzyme that
      inactivates thyroid hormones and is highly expressed during pregnancy and
      development. Mouse Dio3 is imprinted and preferentially expressed from the
      paternal allele in the fetus. We analyzed the human DIO3 genomic region and
      identified a gene (DIO3OS) that is transcribed in the antisense orientation.
      Multiple DIO3OS transcripts are expressed in most tissues. The structure of
      several DIO3OS cDNAs obtained by RT-PCR-based techniques reveals the occurrence
      of numerous splice variants. The exon-intron structures of DIO3OS are similar in
      mouse and human, but the homology of the exonic sequence is very low, except for
      the first exon, and no conserved open reading frame is present. We also detected
      DIO3 transcripts containing additional 5' untranslated sequence and a potential
      alternative upstream promoter for mouse Dio3. Exonic sequence of a Dio3os cDNA
      overlaps with the Dio3 promoter and strong promoter activity in the antisense
      orientation is detected in a genomic fragment located 3' of mouse and human DIO3
      but not in the DIO3 promoter region. These results suggest that the DIO3 gene may
      lie within the structure of the antisense gene, a complex arrangement often
      observed in imprinted loci.

PMID- 14962668
TI  - Identification and characterization of a novel splice variant of mouse and rat
      cytochrome b5/cytochrome b5 reductase.
AB  - Cytochrome b5/cytochrome b5 reductase (cb5/cb5r) is a cytosolic fusion protein
      between the hemoprotein cytochrome b5 and the flavoprotein cytochrome b5
      reductase. We describe the identification and characterization of a novel splice
      variant of cb5/cb5r in the mouse and rat and show that expression of the variant
      is conserved in both species but is not expressed in human tissue.
      Characterization of the exon structure of cb5/cb5r indicated that the variant was
      due to the deletion of the whole of exon 12, thus the variant was named
      cb5/cb5rdelta12. Exon 12 codes for the flavin-adenine dinucleotide binding domain
      of cb5/cb5r. Expression analysis revealed the transcript of cb5/cb5rdelta12 in
      mouse and rat testis, brain, and skeletal muscle and also in the male germ line.
      We postulate that cb5/cb5rdelta12 may function in a dominant negative fashion,
      limiting the amount of damage caused by the production of reactive oxygen species
      by cb5/cb5r.

PMID- 14962669
TI  - Structure, diversity, and evolution of the 45-bp VNTR in intron 5 of the USH1C
      gene.
AB  - Usher syndrome type IC is a rare, autosomal recessive sensorineural disorder
      caused by mutations in the USH1C gene, which encodes a PDZ-domain protein named
      harmonin. The Acadian-specific 216G-->A mutation in exon 3 and a variant 9-repeat
      VNTR allele (designated VNTR(t,t)) in intron 5 are in complete linkage
      disequilibrium. (The usual form of the allele is referred to as VNTR(t).) To gain
      insight into the structure, diversity, and evolution of the VNTR, we analyzed
      individuals from seven different populations, as well as nonhuman primates and
      rodents. The 2-, 3-, and 6-repeat VNTR alleles were the most common. Four novel
      alleles containing 1, 5, 7, and 10 repeats were detected with frequencies of
      0.002, 0.029, 0.005, and 0.001, respectively. The USH1C VNTR region is highly
      conserved among primates, but not between primates and rodents. Five unrelated
      individuals had a 3-repeat VNTR(t,t) allele. Haplotype analysis indicates that
      the 9-repeat VNTR(t,t) and the 3-repeat VNTR(t,t) alleles arose independently.
      However, the 9-repeat VNTR(t,t) and 6-repeat VNTR(t) alleles shared the same
      haplotype, suggesting an expansion from 6(t) to 9(t,t).

PMID- 14962670
TI  - Molecular cloning and characterization of NEU4, the fourth member of the human
      sialidase gene family.
AB  - Several mammalian sialidases have been cloned so far and here we describe the
      identification and expression of a new member of the human sialidase gene family.
      The NEU4 gene, identified by searching sequence databases for entries showing
      homologies to the human cytosolic sialidase NEU2, maps in 2q37 and encodes a 484
      residue protein. The polypeptide contains all the typical sialidase amino acid
      motifs and, apart from an amino acid stretch that appears unique among mammalian
      sialidases, shows a high degree of homology for NEU2 and the plasma membrane
      associated (NEU3) sialidases. RNA dot-blot analysis showed a low but wide
      expression pattern, with the highest level in liver. Transient transfection in
      COS7 cells allowed the detection of a sialidase activity toward the artificial
      substrate 4MU-NeuAc in the acidic range of pH. Immunofluorescence staining and
      Western blot analysis demonstrated the association of NEU4 with the inner cell
      membranes.

PMID- 14962671
TI  - Association of variations in monoamine oxidases A and B with Parkinson's disease
      subgroups.
AB  - Idiopathic Parkinson's disease (PD) is an age dependent, neurodegenerative
      disorder and is predominantly a sporadic disease. A minority of patients has a
      positive family history for PD and the majority of those families exhibit a
      complex mode of inheritance. The monoamine oxidases A and B (MAO-A and -B) genes,
      which are involved in serotonin and dopamine metabolism, are possible candidate
      genes for susceptibility to PD. Previous association studies of MAO-A and -B in
      PD have been inconclusive. To determine the role of MAO-A and -B in the
      development of PD, we screened a sample of 96 patients with familial PD, 164 with
      sporadic PD, and 180 matched normal controls with dinucleotide repeat markers in
      these genes. MAO-A and -B gene polymorphisms were strongly associated with total
      PD (p < 0.00001), familial PD (p < 0.00001), and sporadic PD (p < 0.00001). There
      were no significant differences between familial or sporadic PD with age of onset
      younger than 50 years compared to those with age of onset older than 51 years for
      both MAO-A and -B genes. There was no linkage disequilibrium between these genes
      in male PD and control groups. The frequency of common haplotypes from MAO-A and 
      B was different in PD and control group (p = 0.02). Our data indicate that MAO-A
      and -B may play a role in susceptibility to PD in our sample.

PMID- 14962672
TI  - Differential expression of fibrillin-3 adds to microfibril variety in human and
      avian, but not rodent, connective tissues.
AB  - The human genome contains three fibrillins: FBN1 and FBN2, both well
      characterized, and FBN3, reported only as a cDNA sequence. Like FBN2, the highest
      expression levels of FBN3 were found in fetal tissues, with only low levels in
      postnatal tissues. Immunolocalization demonstrated fibrillin-3 in extracellular
      microfibrils abundant in developing skeletal elements, skin, lung, kidney, and
      skeletal muscle. Unlike the other two fibrillins, FBN3 expression is high in
      brain, and FBN3 is alternatively spliced, removing the exon encoding cbEGF2. Like
      FBN1, FBN3 contains three alternate exons in the 5' UTR. While FBN3 orthologs
      were identified in cow and chicken, Fbn3 appears to have been inactivated in the
      mouse genome, perhaps during chromosome fission events. Located on chromosome
      19p13.3-13.2, FBN3 is a candidate gene for Weill-Marchesani syndrome.

PMID- 14962673
TI  - Functional assessment of the carboxy-terminus of the Wilson disease copper
      transporting ATPase, ATP7B.
AB  - The carboxy-terminus of ATP7B, the protein defective in the copper-transport
      disorder Wilson disease, was investigated with respect to its role in copper
      delivery to the ferroxidase ceruloplasmin. We use yeast as a model system to
      assess the functional capabilities of ATP7B variants. The yeast ferroxidase,
      Fet3p, acquires copper from Ccc2p and cannot function if Ccc2p is impaired;
      expression of wild-type ATP7B in ccc2 yeast complements the iron-deficient
      phenotype. Our results demonstrate that the C-terminus of ATP7B is necessary for
      protein stability, as removal of the nonmembranous terminus leads to reduced
      protein levels and cessation of growth in iron-limited medium. Growth is
      partially restored when an additional three amino acids are present and is near
      wild-type levels when only one-third of the C-terminus is present. Measurement of
      ferroxidase activity is a more sensitive indicator of copper transport function
      and allowed identification of impaired variants not detected with the growth
      assay.

PMID- 14962674
TI  - Functional rescue of vitamin C synthesis deficiency in human cells using
      adenoviral-based expression of murine l-gulono-gamma-lactone oxidase.
AB  - l-Gulono-gamma-lactone oxidase (GULO) is a critical enzyme present in most
      mammalian species that is required for the terminal step in vitamin C
      biosynthesis. Primates are absolutely dependent on exogenously supplied dietary
      vitamin C due to inactivation of the Gulo gene by mutation over 40 million years
      ago. In this study, we report the cloning and expression of the murine l-gulono
      gamma-lactone oxidase cDNA and gene. The cDNA (2.3 kb) encodes an open reading
      frame of 440 amino acids that shows high homology to the rat l-gulono-gamma
      lactone oxidase (>94%). The Gulo gene is 22 kb long and contains 12 exons. The 11
      introns range in size from 479 to 5641 bp. Northern blot analysis revealed high
      expression of Gulo transcript in the liver. To investigate whether metabolic loss
      of vitamin C biosynthesis in human cells can be corrected by heterologous
      expression of GULO, we constructed a first-generation adenoviral vector
      expressing the murine GULO cDNA under the transcriptional control of the murine
      cytomegalovirus (MCMV) early promoter. Low rescue efficiency of Gulo-expressing
      adenoviral constructs and reduced viral growth in HEK293 cells were observed,
      suggesting that overexpression of Gulo may be inhibitory to cell growth.
      Placement of a removable stuffer fragment flanked by lox sites between the MCMV
      promoter and the Gulo gene resulted in efficient vector rescue and normal viral
      replication in parental HEK293 cells and high-level expression of Gulo in HEK293
      cells expressing Cre recombinase. Cells infected with Gulo-expressing vectors
      overexpressed an FAD-containing protein that corresponded in size to that
      predicted for recombinant GULO protein and expressed a functional enzyme as
      measured by the conversion of l-gulono-gamma-lactone to ascorbic acid in cell
      free extracts. The cloning of the murine Gulo cDNA and the construction of Gulo
      expressing adenoviral vectors are vital steps toward determining the role of
      vitamin C in basic metabolism and in disease.

PMID- 14962675
TI  - Inversion, duplication, and changes in gene context are associated with human
      chromosome 18 evolution.
AB  - Human chromosome 18 differs from its homologues in the great apes by a
      pericentric inversion. We have identified a chimpanzee bacterial artificial
      chromosome that spans a region where a break is likely to have occurred in a
      human progenitor and have characterized the corresponding regions in both
      chimpanzees and humans. Interspecies sequence comparisons indicate that the
      ancestral break occurred between the genes ROCK1 and USP14. In humans, the
      inversion places ROCK1 near centromeric heterochromatin and USP14 adjacent to
      highly repetitive subtelomeric repeats. In addition, we provide evidence for a
      human segmental duplication that may have provided a mechanism for the inversion.

PMID- 14962676
TI  - Amino acids runs and genomic compositional biases in vertebrates.
AB  - A compositional analysis of a sample of 50 zebrafish proteins containing at least
      one alanine run and of their open reading frames (ORFs) has been performed. The
      sample of poly(Ala) proteins showed a tendency to have runs of other amino acids
      (His/H, Gln/Q, Ser/S, Pro/P). Their ORFs and the first and second codon positions
      had higher GC contents than a reference gene set. The "universal" correlation
      between the GC content of the first+second and third codon positions (GC1+2 vs
      GC3) does not hold, but I provide an explanation in terms of genomic
      heterogeneity. Significant correlation between AHQS content and GC3 was obtained,
      reflecting codon bias favoring G/C at the third codon position of these amino
      acids. A correspondence analysis (COA) of relative synonymous codon usage showed
      that the poly(Ala) proteins have a biased distribution according to the second
      axis of the COA, which correlates with gene expression in zebrafish. A comparison
      with human is undertaken.

PMID- 14962677
TI  - Evaluation of procedures for amplification of small-size samples for
      hybridization on microarrays.
AB  - Various approaches have been developed for the preparation of samples for gene
      expression monitoring. For Affymetrix chips, a standard protocol is widely used;
      however, this is inefficient for small samples such as laser capture
      microdissections. Several amplification procedures for such samples already
      exist, and our goal was to test two of them: the first is based on random PCR
      amplification, and the second, linear amplification, involves performing the
      standard protocol twice. We analyzed a dilution of a commercially available mouse
      brain total RNA preparation and microdissections from mouse hippocampus and
      striatum. We evaluated the quality of microarray data by analyzing several chip
      parameters and performing multiple comparisons. At the biological level, brain
      microdissections prepared with either method gave similar expression results. At
      the technical level, analysis of the commercial sample showed that random PCR
      amplification is more reproducible, requires smaller RNA input, and generates
      cRNA of higher quality than linear amplification.

PMID- 14962678
TI  - Quantitative PCR for DNA identification based on genome-specific interspersed
      repetitive elements.
AB  - We have designed and evaluated a series of class-specific (Aves), order-specific
      (Rodentia), and species-specific (equine, canine, feline, rat, hamster, guinea
      pig, and rabbit) polymerase chain reaction (PCR)-based assays for the
      identification and quantitation of DNA using amplification of genome-specific
      short and long interspersed elements. Using SYBR Green-based detection, the
      minimum effective quantitation levels of the assays ranged from 0.1 ng to 0.1 pg
      of starting DNA template. Background cross-amplification with DNA templates
      derived from sixteen other species was negligible prior to 30 cycles of PCR. The
      species-specificity of the PCR amplicons was further demonstrated by the ability
      of the assays to accurately detect known quantities of species-specific DNA from
      mixed (complex) sources. The 10 assays reported here will help facilitate the
      sensitive detection and quantitation of common domestic animal and bird species
      DNA from complex biomaterials.

PMID- 14962679
TI  - ExQuest, a novel method for displaying quantitative gene expression from ESTs.
AB  - There is a pressing need for interactive bioinformatics tools that empower
      investigators with the means to extract information and organize it in a
      simplified but meaningful format. A wealth of mammalian gene expression data is
      readily accessible, much of which is based on expressed sequence tags (ESTs).
      Many mammalian ESTs are derived from tissue-specific cDNA libraries in which the
      number of ESTs representing a specific gene approximates the transcriptional
      expression level in the source tissue. Our program ExQuest (Expressional
      Quantification of ESTs) organizes the public EST database (dbEST) into
      hierarchical tissue classes and reports tissue or developmental gene expression
      patterns for both mRNA and genomic sequences. ExQuest also displays tissue
      expression patterns of genes in the context of assembled chromosomes. These
      interactive "transcriptome" maps provide a novel tool for investigating the
      genomic basis of gene expression as well as prioritizing candidate genes within
      genetically mapped mutant and quantitative trait loci.

PMID- 14962681
TI  - Nutritional sciences in Brazil: the pioneer work of institutions and scientists.

PMID- 14962682
TI  - Zinc and iron nutrition in Chilean children fed fortified milk provided by the
      Complementary National Food Program.
AB  - OBJECTIVE: Chilean infants are at risk for isolated zinc and iron deficiencies
      because of a low consumption of animal products in low socioeconomic sectors. In
      1999, the National Complementary Food Program of Chile manufactured a new milk (2
      kg of powdered milk/mo) fortified with iron (Fe; 10 mg/L), zinc (Zn; 5 mg/L), and
      copper (0.5 mg/L) to be provided to infants until age 18 mo and to pregnant
      women. We analyzed the nutrition status of zinc and iron at age 18 mo in infants
      who consumed the fortified cow's milk. METHODS: Forty-two healthy male children
      with normal growth and from lower socioeconomic groups were studied. A nutrition
      survey was conducted; blood and hair samples for Zn in plasma and hair,
      hemoglobin, hematocrit, and serum ferritin were obtained. RESULTS: Mean intakes
      were: energy, 106 +/- 27 kcal. kg(-1). d(-1); protein, 3.8 +/- 1.1 g. kg(-1). d(
      1); Zn, 5.2 +/- 1.9 g/d (0.98 mg Zn/MJ; 68% of World Health Organization
      recommendations); Fe, 11.2 +/- 5.5 mg/d; and dietary fiber, 9.8 +/- 3.9 g/d.
      Plasma Zn in 54.8% of children was no greater than 12.3 microM/L; 36% had hair Zn
      level no greater than 1.23 microM/g and 39% had serum ferritin levels no greater
      than 10 microg/dL (12% were anemic). Hair Zn was correlated to socioeconomic
      level (Spearman's rank correlation, r = -0.53; P < 0.001) and plasma Zn was
      correlated to the z weight/length (r = 0.47; P < 0.05), subscapular skinfold (r =
      0.46; P < 0.05), and Zn intake (r = 0.46; P < 0.05). CONCLUSIONS: The fortified
      powdered cow's milk provided to infants until age 18 mo by the Complementary Food
      Program in Chile favorably affects the Fe status of these children, but possibly
      not the Zn nutrition; we suggest re-evaluation of the levels of Zn fortification.

PMID- 14962683
TI  - Energy expenditure, nutrition status, and body composition in children with
      cystic fibrosis.
AB  - OBJECTIVE: Undernutrition is a frequent complication in patients with cystic
      fibrosis (CF). Elevated energy requirements have been found to be 4% to 33%
      higher than in controls in some studies. Whether or not this is caused by a
      primary defect or energy metabolism is still a matter of controversy. To this
      end, we assessed energy expenditure, nutrition status, and body composition of
      clinically stable CF outpatients. METHODS: Fifteen clinically stable CF patients,
      ages 2 to 15 y, were paired with 15 healthy control children. Measurements
      consisted of anthropometry and body composition. Plasma tocopherol, retinol, and
      hair zinc content were measured. Resting energy expenditure was determined by
      indirect calorimetry. Physical activity and dietary intake were recorded by
      recall methods. RESULTS: Two children were nutritionally at risk according to the
      weight/height index, eight were normal, three were overweight, and two were
      obese. Body composition was similar in both groups. Zinc, tocopherol, and retinol
      levels were low in three, two, and three patients, respectively. Resting energy
      expenditures were 4.7 MJ/d (1127 +/- 220 kcal/d) in CF children and 4.63 MJ/d
      (1108 +/- 191 kcal/d) in control children (P = not significant). Physical
      activity level was sedentary in 86.6% of CF patients; the rest had a light
      physical activity pattern. Energy intake represented 141% of the estimated daily
      energy expenditure. CONCLUSIONS: Non-oxygen-dependent CF children, without acute
      respiratory infection, had resting energy expenditures comparable to those of
      matched controls. Total energy expenditure was similar to or slightly lower than
      that in healthy children. Dietary recommendations for CF patients need to be
      reassessed.

PMID- 14962684
TI  - Fasting breath hydrogen concentration in short bowel syndrome patients with colon
      incontinuity before and after antibiotic therapy.
AB  - OBJECTIVE: Nutrition success in short bowel syndrome (SBS) depends on the intake
      nutrients and the intestinal absorption capacity. An evaluation of energy
      expenditure and oxidation of substrate can be obtained with indirect calorimetry
      by measuring O(2) and CO(2) in the respiration. Elevated colonic fermentation can
      occur in SBS, producing H(2) and CO(2), which can also be eliminated through
      respiration and as a consequence affect the results from indirect calorimetry.
      The objective of this study was to determine the fasting breath H(2)
      concentration and alterations before and after antibiotic therapy in patients
      with severe SBS with colon in continuity. METHODS: The study was conducted in two
      phases. In phase 1, the fasting breath H(2) concentrations were measured in 10
      patients with severe SBS with colon incontinuity and a control group of 10
      healthy volunteers. In phase 2, the fasting breath H(2) concentrations were re
      evaluated after treatment for 7 d with antibiotics in six patients with high
      rates of H(2). The analyses were performed with a gas chromatograph
      (microanalyzer DP; Quintron Instruments, Milwaukee, WI, USA), with results of
      breath hydrogen and methane concentration expressed in parts per million (ppm).
      RESULTS: In phase 1, the levels of fasting breath H(2) were higher in the
      patients with severe SBS with colon incontinuity than in the healthy controls
      (32.00 +/- 17.77 versus 5.30 +/- 3.31 ppm; P < 0.001), with 7 of 10 patients
      presenting levels of H(2) above the normal rate (12 ppm). The presence of an
      ileocecal valve did not modify the results significantly. In phase 2, all six
      patients treated with antibiotics presented normalization in the levels of
      fasting breath H(2) (from 43.50 +/- 6.90 ppm to 1.33 +/- 1.03 ppm; P < 0.001) and
      concomitant improvement in the gastrointestinal symptoms. CONCLUSIONS: In
      relation to the healthy controls, patients with SBS with colon incontinuity
      presented higher levels of fasting breath H(2). Antibiotic therapy normalized the
      levels of fasting breath H(2) and improved the gastrointestinal symptoms. We
      suggest that the breath H(2) test may be performed routinely in patients with SBS
      to diagnose elevated intestinal fermentation, prevent errors in the
      interpretation of the indirect calorimetry, and treat eventual associated
      gastrointestinal symptoms.

PMID- 14962685
TI  - Assessment of the nutrition status of patients with Huntington's disease.
AB  - OBJECTIVE: The purpose of the present study was to compare the nutrition status
      of patients with Huntington's disease (HD) with that of control subjects by
      analyzing anthropometric and biochemical indicators, energy, and macronutrient
      intake and to determine which indicators are most altered in HD patients.
      METHODS: We assessed the nutrition status of 25 HD patients and 25 age- and sex
      matched controls by measuring anthropometric and biochemical indicators. Food
      intake data were obtained by the 3-d record method to assess mean daily energy
      and macronutrient intake. We studied variables reported by the patients such as
      increased or decreased appetite, mastication difficulties, and solid food and
      liquid food dysphagia. A neurologist assessed the clinical features of HD
      patients by using the Unified Huntington's Disease Rating Scale. RESULTS: HD
      patients showed significantly lower anthropometric variables but significantly
      higher kilocalorie intake. Among the subjective variables analyzed, patient
      referred weight loss, increased appetite, mastication, and solid food dysphagia
      were significantly more frequent in HD patients than in controls. We also found
      relations between motor disability and some anthropometric parameters in HD
      patients. In particular, we found a significant correlation between total motor
      disability score and body mass index and arm muscle circumference (r = -0.464 and
      -0.445, respectively; P < 0.05) and with percentage of body fat (r = -0.496, P =
      0.012). CONCLUSIONS: It is of the utmost importance to identify nutritional
      alterations in HD patients and to find strategies to cover their kilocalorie and
      nutrient requirements to improve their quality of life.

PMID- 14962686
TI  - Intraluminal irrigation with fibers improves mucosal inflammation and atrophy in
      diversion colitis.
AB  - OBJECTIVE: We investigated the effect of irrigating the colorectal mucosa of
      patients with a colostomy using a solution of fibers. METHODS: Eleven patients
      (10 male and 1 female; mean age, 34 y; age range, 16-49 y) with loop colostomy
      due to trauma underwent endoscopic evaluation of the rectum and the proximal and
      distal mucosa from the colostomy. An endoscopic score (range, 0-10) was used to
      quantify the intensity of the inflammation at the mucosa. Biopsies were taken
      from the colostomy border and from the rectum. The mean crypt depth of the five
      best-oriented glands was registered. Then the diverted colorectal segment was
      irrigated with a solution containing 5% fibers (10 g/d) for 7 d. The patients
      underwent repeated endoscopic and biopsy procedures, and then the colostomy was
      closed. RESULTS: The endoscopic score was higher (P < 0.01) at the distal border
      (2, 0-5) and the rectum (4, 1-10) when compared with the proximal border (0, 0
      1). After treatment, the score at the diverted colon (1, 0-2) diminished (P =
      0.03). The macroscopic score of the rectum also decreased after the infusion (4,
      1-10, versus 3, 0-4; P = 0.03). Crypt depth at the proximal mucosa was higher
      than at the diverted mucosa (301 +/- 36 microm versus 205 +/- 76 microm; P <
      0.01). After treatment, crypt depth at the diverted mucosa (280 +/- 64 microm)
      increased (P = 0.03). The rectum mucosa did not change before and after the
      treatment. CONCLUSION: Irrigation with fibers improves inflammation at the
      defunctionalized colon.

PMID- 14962687
TI  - Comparison between the effects of soy milk and non-fat cow milk on lipid profile
      and lipid peroxidation in patients with primary hypercholesterolemia.
AB  - OBJECTIVE: This study assessed whether the consumption of soy milk could add
      significantly to the lipid profile and lipid peroxidation in comparison with non
      fat milk. METHODS: A double-blind, randomized, crossover study was conducted on
      60 outpatients with primary hypercholesterolemia following a lipid-lowering diet
      for at least 6 wk. Lipid profile was obtained at baseline and at 6 and 12 wk,
      with the patients randomly assigned to receive initially 1 L/d of soy milk or non
      fat cow milk for 6 wk. Lipid peroxidation was estimated by plasma thiobarbituric
      reactive substances. Apolipoprotein E genotypes were examined by polymerase chain
      reaction restriction fragment length polymorphism. RESULTS: The soy milk diet was
      associated with low-density lipoprotein cholesterol reduction (baseline = 157 +/-
      5 mg/dL; soy milk = 148 +/- 4 mg/dL; non-fat cow milk = 158 +/- 4 mg/dL; P <
      0.05, soy milk versus other treatments) and with high-density lipoprotein
      cholesterol increase (baseline = 58 +/- 2 mg/dL; soy milk = 62 +/- 2 mg/dL; non
      fat cow milk = 57 +/- 2 mg/dL; P < 0.05, soy milk versus other treatments). In
      addition, plasma thiobarbituric reactive substances were reduced by the soy milk
      diet (baseline = 1.82 +/- 0.12 nM/L; soy milk = 1.49 +/- 0.09 nM/L; non-fat cow
      milk = 1.91 +/- 0.11 nM/mL; P < 0.05, soy milk versus non-fat cow milk). Changes
      in lipid profile were not influenced by APOE genotypes. CONCLUSIONS: These
      results indicate that soy milk as part of a lipid-lowering diet has beneficial
      effects in improving lipid profile and reducing lipid peroxidation.

PMID- 14962688
TI  - Iron, zinc, and copper: contents in common Chilean foods and daily intakes in
      Santiago, Chile.
AB  - OBJECTIVES: We determined the iron (Fe), zinc (Zn), and copper (Cu) contents of
      common Chilean foods and assessed the intakes of these elements in a population
      living in Santiago, Chile. METHODS: We selected foods most consumed by a Chilean
      population (n = 108). We performed wet digestion of the sample by using nitric,
      perchloric, and sulfuric acids. Fe, Zn, and Cu were determined by atomic
      absorption spectrophotometry. Fe, Zn, and Cu intakes were evaluated by a dietary
      survey (24-h recall questionnaire for 4 non-consecutive days) in a representative
      sample of the population of Santiago, Chile (n = 252 subjects). RESULTS: Fe
      intakes (mg/d) were 7.8 +/- 9.6 (in infants), 8.1 +/- 5.3 (in 1- to 10-y-olds),
      15.1 +/- 7.3 (11- to 19-y-old males), 9.5 +/- 4.3 (11- to 19-y-old females), 13.5
      +/- 6.5 (20- to 64-y-old males), 9.1 +/- 3.9 (20- to 64-y-old females), 11.4 +/-
      4.9 (> or =65-y-old males), and 11.3 +/- 5.0 (> or =65-y-old females). Zn intakes
      (mg/d) were 3.8 +/- 1.8 (infants), 6.2 +/- 3.1 (1- to 10-y-old subjects), 8.9 +/-
      4.1 (11- to 19-y-old males), 5.7 +/- 2.0 (11- to 19-y-old females), 7.6 +/- 3.4
      (20- to 64-y-old males), 6.4 +/- 3.5 (20- to 64-y-old females), 6.6 +/- 2.9 (> or
      =65-y-old males), and 6.9 +/- 2.4 (> or =65-y-old females). Cu intakes (mg/d)
      were 0.5 +/- 0.3 (infants), 0.8 +/- 0.5 (1- to 10-y-old subjects), 1.4 +/- 0.7
      (11- to 19-y-old males), 1.2 +/- 0.3 (11- to 19-y-old females), 0.9 +/- 0.4 (20-
      to 64-y-old males), 1.0 +/- 0.4 (20- to 64-y-old females), 1.1 +/- 0.3 (> or =65
      y-old males), and 0.9 +/- 0.4 (> or =65-y-old females). CONCLUSIONS: Fe
      deficiency was greater in infants and women of fertile age. All age and sex
      groups had a high risk of Zn deficiency, whereas adults of both sexes had a
      moderate increased risk of Cu deficiency.

PMID- 14962689
TI  - Effects of a leucine-rich diet on body composition during nutritional recovery in
      rats.
AB  - OBJECTIVE: Protein malnutrition is characterized by a number of morphologic and
      physiologic alterations, including intestinal mucosal atrophy and impaired
      nutrient absorption. Impaired absorption accentuates nutritional deficiency and
      accelerates body weight loss and changes in body chemistry. Because leucine is a
      ketogenic and oxidative amino acid and stimulates the protein synthesis, we
      examined the ability of young rats to recover from protein malnutrition by
      feeding them a control balanced or a leucine-rich diet for 60 d. METHODS: At the
      end of the 60-d period, body, liver, and muscle weights; glucose, methionine, and
      leucine intestinal absorption; and carcass chemical composition were evaluated.
      RESULTS: Body weight gain was higher in the control balanced and leucine-rich
      groups than in control rats, indicating that adequate refeeding allows body
      weight to recover in these groups. Methionine and glucose absorptions were
      impaired in malnourished rats but were restored after nutritional recovery. The
      leucine-rich diet resulted in an increase in carcass collagen nitrogen but
      maintained the carcass structural nitrogen. CONCLUSIONS: These results indicated
      that leucine supplementation during nutritional recovery from protein
      malnutrition improves protein carcass restoration. However, the precise mechanism
      of the leucine effects involved in this response remains to be elucidated.

PMID- 14962690
TI  - Effect of palatable hyperlipidic diet on lipid metabolism of sedentary and
      exercised rats.
AB  - OBJECTIVE: The present study was designed to examine 1) whether continuous
      feeding with a palatable hyperlipidic diet and cycling this diet with chow diet
      would affect lipid and carbohydrate metabolism in a similar way; and 2) whether
      the effect of chronic exercise on lipid and carbohydrate metabolism would be
      modified by these diet regimens. METHODS: Male 25-d-old Wistar rats were assigned
      to one of six groups: sedentary rats fed with chow diet; exercised (swimming 90
      min/d, 5 d/wk) rats fed with chow diet; sedentary rats fed with a palatable
      hyperlipidic diet; exercised rats fed with the palatable hyperlipidic diet;
      sedentary rats fed with food cycles (four cycles alternating the chow and
      hyperlipidic diets weekly); and exercised rats fed with food cycles. After 8 wk
      of treatment, the animals were killed 24 h after the last exercise session.
      RESULTS: The hyperlipidic diet and food cycles schedules caused similar increases
      in body weight gain, carcass lipogenesis rate and adiposity, lipid content of the
      liver and gastrocnemius muscle, and serum total lipid, triacylglycerol, insulin,
      and leptin levels. The exercise attenuated body weight gain, adipose tissue mass,
      and serum triacylglycerol, insulin, and leptin levels similarly in the
      hyperlipidic and food cycles groups. Carcass lipogenesis rate was not affected by
      exercise in any of the three groups. CONCLUSIONS: The data showed that the
      continuous intake of a hyperlipidic palatable diet for 8 wk and the alternation
      of the high-fat intake with periods of chow intake cause obesity and affected
      lipid metabolism in a similar way. Chronic exercise attenuated body weight gain
      and adiposity and improved serum lipid concentrations in both high-fat feeding
      regimens.

PMID- 14962691
TI  - Effects of L-arginine-enriched total enteral nutrition on body weight gain, tumor
      growth, and in vivo concentrations of blood and tissue metabolites in rats
      inoculated with Walker tumor in the kidney.
AB  - OBJECTIVE: We evaluated the effects of l-arginine-enriched total enteral
      nutrition (LATEN) on tumor-free and right kidney tumor-bearing rats through the
      determination of in vivo concentrations of metabolites to better understand
      intermediary metabolism in this model. METHODS: Rats were individually housed in
      wire cages within a controlled environment (25 degrees C and 50% relative
      humidity) and exposed to a 12-h light-and-dark cycle. Rats comprised the
      following groups: tumor-free on enteral nutrition plus l-amino acid (n = 8);
      tumor-free on enteral nutrition plus l-arginine (n = 8); tumor bearing on enteral
      nutrition plus l-amino acids (n = 8); and tumor bearing on enteral nutrition plus
      l-arginine (n = 8). Rats had their right kidneys inoculated with saline or tumor
      cells and were subjected to laparotomy or gastrostomy on day 1 and received chow
      diet for the next 2 days. Gastrostomy with enteral nutrition was performed on
      days 3 to 9. On day 9, body weight gain, tumor growth as volume, in vivo blood
      (microM/mL), and tissue (microM/g) metabolite concentrations were determined. The
      Mann-Whitney U test was used to test significance. RESULTS: LATEN in tumor-free
      rats decreased liver (0.25 +/- 0.03 versus 0.13 +/- 0.03 micromol/g, P < 0.05)
      and right kidney (0.13 +/- 0.1 versus 0.04 +/- 0.00 micromol/g, P < 0.05) ketone
      body concentrations. LATEN in tumor-bearing rats decreased blood pyruvate (0.17
      +/- 0.01 versus 0.10 +/- 0.008 microM/mL, P < 0.005), lactate (5.2 +/- 0.3 versus
      2.9 +/- 0.28 microM/mL, P < 0.01), and glucose (6.4 +/- 0.8 versus 3.7 +/- 0.5
      microM/mL, P < 0.05). Glucose concentrations decreased in liver (13.9 +/- 2.0
      versus 4.89 +/- 0.6 microM/g, P < 0.005) and tumor (3.5 +/- 0.8 versus 1.41 +/-
      0.3 microM/g, P < 0.05). There were no changes in body weight gain (21 +/- 2.0
      versus 30.3 +/- 3.6 g) or tumor growth (1.53 +/- 0.1 versus 1.26 +/- 0.01 cm(3)).
      CONCLUSIONS: LATEN decreased ketone body concentrations in liver and kidney in
      tumor-free rats, possibly due to lower ketogenesis and decreased kidney uptake.
      In tumor-bearing rats, LATEN decreased lacticemia and glycemia and pyruvate blood
      concentrations. LATEN also reduced liver and tumor glucose concentrations in
      tumor-bearing animals. The possibility of LATEN-induced insulin and insulin-like
      growth factor-1 liberation signaling these changes is discussed.

PMID- 14962692
TI  - Diets rich in saturated and polyunsaturated fatty acids: metabolic shifting and
      cardiac health.
AB  - OBJECTIVE: The aim of this study was to determine the effects of diets rich in
      saturated and polyunsaturated fatty acids on metabolic pathways and the relation
      of metabolic shifting to oxidative stress in cardiac tissue. METHODS: Male Wistar
      rats (age, 60 d; n = 10) were fed with a control low-fat diet, a diet rich in
      saturated fatty acids (SFAs), or a diet rich in polyunsaturated fatty acids
      (PUFAs). After 5 wk of treatment, sera were used for protein and lipid
      determinations. Protein, glycogen, triacylglycerol, lactate dehydrogenase,
      citrate synthase, beta-hydroxyacyl coenzyme-A dehydrogenase, catalase,
      glutathione peroxidase, superoxide dismutase, lipoperoxide, and lipid
      hydroperoxide were measured in cardiac tissue. RESULTS: The SFA group had higher
      triacylglycerol, cholesterol, low-density lipoprotein cholesterol, and
      atherogenic index (ratio of cholesterol to high-density lipoprotein) than did the
      PUFA and control groups. The PUFA group had low serum cholesterol,
      triacylglycerol, and low-density lipoprotein cholesterol as compared with the SFA
      group. SFA increased myocardial lipid hydroperoxide and diminished glutathione
      peroxidase. Despite the beneficial effects on serum lipids, the PUFA diet led to
      the highest levels of myocardial lipoperoxide and lipid hydroperoxide and
      diminished superoxide dismutase and catalase activities. The PUFA effects were
      related to increased feed efficiency, increased susceptibility to
      lipoperoxidation, and metabolic shifting in cardiac tissue. PUFA elevated
      triacylglycerol levels and decreased myocardial glycogen concentrations. The
      ratios of lactate dehydrogenase to citrate synthase and beta-hydroxyacyl coenzyme
      A dehydrogenase to citrate synthase were increased, indicating myocardial
      reduction of tricarboxylic acid cycle. CONCLUSIONS: PUFAs have been recommended
      as a therapeutic measure in preventive medicine to lower serum cholesterol, but
      PUFAs increased oxidative stress in the heart by providing cardiac susceptibility
      to lipoperoxidation and shifting the metabolic pathway for energy production. The
      control diet, which was much lower in calories and fat, produced better overall
      clinical outcomes, better fat profiles, and less oxidative stress than did the
      diets rich in fatty acids.

PMID- 14962693
TI  - Mineral and bone mass changes during pregnancy and lactation.

PMID- 14962694
TI  - Don't bite the hand that feeds you.

PMID- 14962695
TI  - Dietary long-chain omega-3 fatty acids and anti-inflammatory action: potential
      application in the field of physical exercise.

PMID- 14962696
TI  - What should the European Journal of Internal Medicine publish? Time for a new
      editorial policy.

PMID- 14962697
TI  - Angiogenesis in human cancer: implications in cancer therapy.
AB  - Angiogenesis represents an essential step in tumor proliferation, expansion, and
      metastasis. Tumor cells may express both proangiogenic and/or antiangiogenic
      factors. Under normal circumstances, angiogenesis is controlled through the
      equilibrium of these factors. This balance is disrupted in malignancy, resulting
      in promotion of angiogenesis. Among angiogenic molecules, VEGF appears to have a
      central role in the angiogenic process: it is the target of many proangiogenic
      factors, but it also regulates molecules that are implicated in endothelial
      proliferation. It has been suggested that VEGF may be a proximate angiogenic
      factor through which others act. The degree of angiogenesis and the expression of
      angiogenic factors have been associated with prognosis in several human
      neoplasms. In addition, angiogenesis offers a theoretically selective target for
      anticancer therapy, since it is only required for wound healing, endometrial
      proliferation, and pregnancy in healthy individuals. Antiangiogenic cancer
      treatment is still largely experimental and its clinical potential is currently
      being studied in clinical trials. Thalidomide, a drug with antiangiogenic
      properties, has shown significant efficacy in patients with relapsed or
      refractory multiple myeloma. In addition, an anti-VEGF monoclonal antibody
      prolonged survival in patients with advanced colorectal and renal cell carcinoma.
      Although these results are encouraging, selection of patients is essential in
      order to target populations most likely to benefit from antiangiogenic therapy.

PMID- 14962698
TI  - Azithromycin therapy in patients with chronic Chlamydia pneumoniae infection and
      coronary heart disease: immediate and long-term effects on inflammation,
      coagulation, and lipid status in a double-blind, placebo-controlled study.
AB  - Background: An association between Chlamydia pneumoniae (Cp) infection and
      coronary heart disease (CHD) has already been reported. We investigated the
      relationship between Cp infection and other risk factors in CHD patients, as well
      as the effects of azithromycin treatment. Methods: We studied 38 patients with Cp
      infection (Cp-pos) and 15 without (Cp-neg). Cp-pos patients had, both at
      inclusion and 2 years prior to inclusion, elevated Cp-specific IgA-antibodies,
      with or without the presence of pharyngeal Cp by polymerase chain reaction (PCR)
      detection. Blood was analyzed for Cp-antibodies, interleukin-6, interleukin-1
      receptor antagonist (IL-1ra), CRP, orosomucoid, fibrinogen, leukocytes, PAI-1,
      tPA, von Willebrand factor (vWf), platelet count and aggregation, and lipids. Cp
      pos patients were randomized to placebo or oral azithromycin, 500 mg on day 1 and
      then 250 mg/day for 4 days, with repeated therapy after 3 weeks. Blood was taken
      immediately, as well as 3 months and 2 years after therapy. Results: CRP and IL
      1ra levels were higher in Cp-pos than in Cp-neg patients: median, interquartile
      range 8.5 (3.0-20) vs. 2.0 (1.0-3.8) mg/l, and 316 (165-404) vs. 178 (118-195)
      ng/l, p=0.0006 and p=0.002, and platelet aggregation was lower: 4.8 (2.9-6.4) vs.
      8.1 (4.7-11.4) Omega, p<0.05. tPA levels increased in azithromycin-treated
      patients between entry and 3-month follow-up: mean+/-S.D. 3.7+/-4.2 vs. 1.0+/-2.1
      microg/l, p<0.05. Other variables did not differ. Conclusions: Cp infection was
      associated with increased inflammatory activity and lower platelet aggregability,
      suggesting that inflammation may be of greater pathophysiological importance than
      platelet activity in these patients. Although an effect on Cp infection was not
      shown, azithromycin may have a positive effect on fibrinolysis, as increased
      levels of tPA were observed in the treatment group.

PMID- 14962699
TI  - Low-dose interferon-alpha accelerates atherosclerosis in an LDL receptor
      deficient mouse model.
AB  - Background: Solid evidence suggests that atheroscleosis is associated with immune
      reactions. Most of the activated T cells in the plaque are T helper 1 subtype
      (Th1), which secrete interferon-gamma (IFN-gamma), now generally accepted as a
      proatherogenic cytokine. Interferon-alpha (IFN-alpha) has been found to inhibit
      the secretion of IL-12 and IFN-gamma and to increase IL-10 production. It may,
      therefore, be atheroprotective. The aim of the present study was to clarify the
      effect of IFN-alpha on atherogenesis in a transgenic mouse model of
      atherosclerosis. Methods: 8-week-old low-density lipoprotein (LDL) receptor
      deficient mice were allocated randomly into treatment and control groups (n=13
      each). The treatment group received 1000 units of IFN-alpha i.p. every other day
      for 5 weeks and the control mice received 0.9% NaCl. The mice were fed a Western
      diet. Results: The IFN-alpha-treated and the control mice showed a similar weight
      gain (mean 3.9+/-1.0 g vs. 3.4+/-1.8 g, respectively). Treatment with IFN-alpha
      significantly increased the plasma cholesterol levels in both treated and
      untreated mice (mean 31.03+/-5.53 mmol/l vs. 24.91+/-6.03 mmol/l, respectively;
      p<0.022) as well as the plasma triglyceride levels (mean 4.79+/-1.57 mmol/l vs.
      3.10+/-1.85 mmol/l, respectively; p<0.033). The IFN-alpha treated mice had a
      significantly increased atherosclerotic plaque area (mean 61,590+/-22,368
      microm(2) vs. 37,272+/-15,469 microm(2), respectively; p<0.008). Conclusion: The
      putative atheroprotective effect of IFN-alpha by the decrease in IL-10 and IFN
      gamma is abolished by hyperlipidemia. Therefore, the net effect of IFN-alpha in
      this murine model is the exacerbation of atherosclerosis.

PMID- 14962700
TI  - The incidence of oral Gram-negative bacteria in patients with Parkinson's
      disease.
AB  - Background: Parkinson's disease is a common neurodegenerative disorder that
      affects an increasing number of older people every year. Dysphagia is not only a
      common feature, but one that results in poor nutrition and an increased risk of
      bronchopneumonia. Previous work has suggested that the oral flora is altered in
      patients with oral pathology. Methods: Fifty patients were assessed to quantify
      the incidence of oral Gram-negative bacteria. Results: Sixteen of the patients
      with Parkinson's disease were found to have six different Gram-negative bacilli
      in their oral cavities. The 20 different Gram-negative bacteria present were
      Escherichia coli (n=7), Klebsiella spp. (n=3), Kluyvera spp. (n=3), Serratia spp.
      (n=3), Proteus spp. (n=2) and Enterobacter spp. (n=2). We found that the oral
      cavity of 16 (32%) of the patients with Parkinson's disease was abnormally
      colonised with Gram-negative bacteria and that Gram-negative bacteria were more
      likely to occur in those patients in whom oromuscular dysfunction was present
      (88% vs. 21%; p<0.05). Conclusion: Further work is required to determine the
      association between oral flora and the pathogenic organisms found in aspiration
      pneumonia as well as work on innovative treatments to reduce oral Gram-negative
      bacteria in those patients at particular risk of aspiration pneumonia.

PMID- 14962701
TI  - Bronchiectasis in secondary care: a comprehensive profile of a neglected disease.
AB  - Background: Bronchiectasis is poorly characterised in secondary care. Methods:
      Over 6 months, 410 bronchiectasis patients attended our clinics. One hundred
      randomly selected patients were characterised in detail. Results: Patients had a
      mean and standard error of mean (S.E.M.) age of 57 (2) years and a median and
      interquartile range (IQR) of three (two to four) reviews in the last 12 months.
      Aetiologies identified included tuberculosis (n=15), childhood pneumonia (n=7),
      fibrosis (n=6), connective tissue disease (n=6), whooping cough (n=5), childhood
      measles (n=4) and others (n=5). There was widespread use of inhaled therapy.
      Treatments included oral antibiotics (n=77), corticosteroid courses (n=27) and
      intravenous antimicrobials (n=27, 12 domicillary) in the last year. Thirty
      patients had hospital admissions (13 because of the inability to administer
      domicillary antibiotics). Haemophilus influenzae and Pseudomonas spp. were the
      commonest bacterial isolates. Patients culturing Pseudomonas spp. were older and
      had had more reviews and intravenous antibiotic courses. Conclusions:
      Bronchiectasis imposes a considerable burden on hospital services. Patients
      culturing Pseudomonas spp. impose a greater burden. Aetiology is often unknown.
      Therapies with unproven benefit are often used.

PMID- 14962702
TI  - The skin is the clue.
AB  - A 67-year-old woman presented with aseptic osteomyelitis and palmoplantar
      pustular psoriasis. The diagnosis of SAPHO syndrome was made. Treatment with
      pamidronate led to symptomatic improvement.

PMID- 14962703
TI  - Severe enoxaparin-induced thrombocytopenia complicated by pulmonary emboli.
AB  - Low molecular weight heparins (LMWH) have been widely used in the last decade,
      especially for prophylaxis of deep venous thrombophlebitis. Enoxaparin-induced
      thrombocytopenia is rarely encountered, in contrast to its high prevalence among
      patients treated with unfractionated heparin. We report a case of a patient who
      was admitted because of a pulmonary embolus due to proximal deep vein
      thrombophlebitis 2 weeks after surgery, despite prophylaxis with low-dose
      enoxaparin after prostatectomy. The patient's original normal platelet count
      (255,000/microl) dropped to 30,000/microl while on enoxaparin therapy. Testing
      for antibodies against heparin was positive. Warfarin was initiated and an
      inferior vena caval filter was inserted. Within a few days, platelet count
      increased to 100,000/microl, pulmonary status improved, and the patient was
      released in good clinical condition. Heparin-induced thrombocytopenia (HIT) is
      discussed, as are alternative treatments for unfractionated heparins and LMWH.

PMID- 14962704
TI  - DRESS syndrome associated with HHV-6 reactivation.
AB  - Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a
      serious condition associated with drugs. We report the case of a patient with a
      febrile skin eruption associated with eosinophilia and hepatitis following drug
      intake. Serological testing for human herpes virus 6 (HHV-6) was positive. Skin
      biopsy was compatible with DRESS syndrome. Despite discontinuation of all
      medications and initiating of corticosteroids, the patient developed acute renal
      and cardiac failure leading to death. Diagnosis, pathophysiology, and treatment
      are discussed.

PMID- 14962705
TI  - Necrotic cellulitis by Serratia plymuthica.
AB  - This case report describes an uncommon cellulitis caused by Serratia plymuthica
      in a patient treated with steroids. The evolution was favorable after surgical
      exploration with debridement and antibiotic treatment. This is the first case of
      necrotic cellulitis caused by S. plymuthica described in the literature.

PMID- 14962706
TI  - Intracardiac thrombi in primary antiphospholipid syndrome: two case reports.
AB  - We describe two patients who developed stroke and ischemia of the left lower
      limb, related to intracardiac thrombi, as the first manifestation of primary
      antiphospholipid syndrome (PAPS). Transesophageal echocardiography (TEE) revealed
      intracardiac thrombi as abnormal hyperechogenic, nonmobile masses, firmly
      attached to the left atrial appendage and the anterior part of the mitral
      annulus, respectively. Our patients received high-intensity oral anticoagulant
      therapy (INR 3.0-4.0), which resulted in the rapid disappearance of clinical
      symptoms, without subsequent recurrence of thromboembolic manifestations, and the
      disappearance of intracardiac thrombi on TEE. Our findings underscore that PAPS
      should be suspected in patients presenting with intracardiac thrombi, even if
      they have no previous history of thromboembolic disorders. Moreover, because
      intracardiac thrombi may precede other manifestations of PAPS, this finding in
      young patients without underlying heart disease should invoke a search for both
      antiphospholipid and anticardiolipin antibodies.

PMID- 14962707
TI  - Left thalamo-peduncular abscess caused by Listeria monocytogenes in a homeless
      patient.

PMID- 14962708
TI  - Localized hepatic tuberculosis.

PMID- 14962709
TI  - Torsades de pointes and hypothyroidism.

PMID- 14962710
TI  - Is local control necessarily an indicator of quality?

PMID- 14962711
TI  - Long-term efficacy of the CHVmP/BV regimen used for aggressive non-Hodgkin's
      lymphoma in three randomised EORTC trials.
AB  - We analysed data from 936 newly-diagnosed patients with advanced, aggressive non
      Hodgkin's lymphoma (NHL) treated in three randomised European Organisation for
      Research and Treatment of Cancer (EORTC) trials performed between 1980 and 1999
      (median follow-up of 8.7 (0.2-20.4) years). The CHOP-like regimen CHVmP/BV
      (cyclophosphamide, doxorubicin, teniposide and prednisone with bleomycin and
      vincristine at mid-interval), was compared with CHVmP (CHVmP/BV without bleomycin
      and vincristine), ProMACE-MOPP (methotrexate, doxorubicin, cyclophosphamide,
      etoposide, mechlorethamide, vincristine, procarbazine and prednisone) and
      CHVmp/BV with additional, autologous stem-cell transplantation, respectively.
      Overall, treatment with CHVmP/BV resulted in a better long-term outcome with 63%
      complete responses being observed and an overall survival (OS) of 59 and 43% at 5
      and 10 years, respectively. Remarkably, OS after CHVmP/BV improved across the
      trials, even after stratifying for the International Prognostic Index (IPI). This
      finding could not be directly related to better salvage treatments during the
      last decade. Selection bias appears to be responsible: stepwise corrections for
      small differences in inclusion criteria eliminated the difference in OS,
      especially when histological subgroups were studied. This systemic review
      underlines the difficulties encountered in retrospective sub-set analyses and the
      biases that can be introduced when recent studies are compared with older ones.

PMID- 14962712
TI  - Monitoring different stages of breast cancer using tumour markers CA 15-3, CEA
      and TPA.
AB  - The ability of the tumour markers Cancer Antigen 15-3 (CA 15-3), Carcinoembryonic
      Antigen (CEA), and Tissue Polypeptide Antigen (TPA) to signal progression in
      breast cancer patients was investigated in this study. Marker interpretation
      considered the analytical variation, intra-individual biological variation, and
      the rate of increase. Patient cohorts were as follows: (A) 90 stage II breast
      cancer patients who were monitored postoperatively, (B) 204 recurrent breast
      cancer patients who were monitored during first-line chemotherapy, and (C) 112
      patients who were monitored during the time period after first-line chemotherapy.
      The sensitivity for progression was 44% (cohort A), 69% (cohort B), and 68%
      (cohort C) without any false progression signals. Marker lead-times exceeded 3
      months in 20% (cohort A) and 27% (cohort C) of patients. Marker lead-times were 1
      6 months among 33% of the patients receiving first-line chemotherapy (cohort B).
      Trials are necessary to determine whether tumour marker-guided therapy has any
      prognostic impact. The data suggest that tumour marker information may be used to
      stop ineffective treatments and reduce unnecessary adverse effects.

PMID- 14962713
TI  - Using loco-regional recurrence as an indicator of the quality of breast cancer
      treatment.
AB  - The aim of our study was to compare the loco-regional recurrence (LRR) rates
      after breast-conserving surgery and mastectomy between the time periods of 1985
      1992 and 1993-1999. The first period reflects the early experiences with breast
      conservation. The second period covers the years when a mammographical screening
      programme was introduced for women 50-69 years of age. We collected data on 1212
      patients with 1264 resectable breast cancers (i.e. stage I, IIA, IIB and IIIA),
      of which 385 were removed by breast conserving surgery and 879 by mastectomy.
      During follow-up, 47 loco-regional recurrences developed after breast
      conservation, and 67 after mastectomy. The 5- and 10-year loco-regional
      recurrence rates were 5.7% (95% Confidence Interval (CI) 4.0-7.4) and 11.0% (95%
      CI 8.0-14.0), respectively, after mastectomy and 7.3% (95% CI 4.5-10.1) and 15.8%
      (95% CI 11.2-20.4), respectively, after breast conservation. The 8-year loco
      regional recurrence rate after breast conservation decreased from 20.1% (95% CI
      14.7-26.5) in the period of 1985-1992 to 5.4% (95% CI 1.8-9.0) in the period of
      1993-1999 (P=0.0018). Despite the more favourable stage distribution of the
      patients undergoing mastectomy, no significant decrease was observed in the LRR
      risk in the latter period (P=0.18). Improvements in patient selection and
      treatment techniques are the most likely explanations of the decreasing LRR rate
      after breast conservation in our teaching hospital.

PMID- 14962714
TI  - Aberrant expression of interleukin-7 (IL-7) and its signalling complex in human
      breast cancer.
AB  - Interleukin-7 (IL-7), a haematopoietic growth factor, is known to induce the
      differentiation and proliferation of some haematological malignancies including
      certain types of leukaemias and lymphomas. However, little is known about its
      role in solid tumours, including breast cancer. In this study, the expression
      level of IL-7, IL-7 receptor (IL-7R) and their downstream signalling molecules,
      including the Janus kinases (Jak-1 and Jak-3), phosphoinositide 3-kinase (PI3-K)
      and signal transducers and activators of transcription (Stat-5) were analysed
      using the reverse transcriptase-polymerase chain reaction (RT-PCR), real-time
      quantitative PCR and immunohistochemistry in a cohort of patients with breast
      cancer. The results were analysed in relation to tumour grade, TNM stage,
      patients' prognosis (using the Nottingham Prognostic Index (NPI)) and survival.
      The levels of expression of IL-7, IL-7R, Jak-1, Jak-3, PI3-K and Stat-5 were
      significantly higher in the most aggressive tumours. With the exception of Stat-5
      expression, the transcript copies of IL-7 and all other signalling molecules were
      higher in patients with the worst prognoses (NPI3) and in patients who died from
      breast cancer after 72 months of follow-up. This aberrant expression of IL-7 and
      its signalling intermediates in invasive breast cancers could have significant
      diagnostic and prognostic implications. Measuring these molecules in breast
      cancer tissues may provide, for the first time, important molecular indicators of
      tumour differentiation, aggressiveness, nodal status, prognosis and patient
      survival.

PMID- 14962715
TI  - Prognostic value of facilitative glucose transporter Glut-1 in oral squamous cell
      carcinomas treated by surgical resection; results of EORTC Translational Research
      Fund studies.
AB  - Hypoxia in tumours of the oral cavity has not been extensively investigated with
      regard to clinical outcome and prognosis. The expression of the facilitative
      glucose transporter, Glut-1, has been shown to be related to hypoxia in tumours
      at other sites. The aim of the present study was to investigate the relationship
      between Glut-1 expression and clinical outcome in a series of oral squamous cell
      carcinomas. A retrospective series of 54 cases of oral squamous cell carcinomas
      with known clinical outcome and treated by one surgeon over a period of 6 years
      was used in the study. A representative section from each case was stained
      immunohistochemically with an antibody against Glut-1. The stained sections were
      then assessed independently by two observers using a semi-quantitative method.
      The relationship between these results and the clinical outcomes of local
      recurrence, regional lymph-node metastasis and disease-free survival were
      examined. Glut-1 staining was observed in most of the tissue specimens and all of
      the few sections with demonstrably necrotic areas histologically. Some showed
      more prominent staining in the epithelial islands of the tumour than others.
      However, the intensity of staining was variable. There was a significant
      relationship between those tumours which demonstrated intense staining and
      recurrence overall (chi(2)=6.18, P=0.032). This relationship was strongest in
      relation to regional lymph-node recurrence (chi(2)=10.19, P=0.005). A significant
      relationship between disease-related death and intense Glut-1 staining was also
      observed (chi(2)=11.67, P=0.002). In conclusion, the results of this study
      indicate a relationship between Glut-1 expression and disease progression of oral
      cancer and could indicate a need for neoadjuvant chemoradiotherapy for those
      tumours demonstrating intense Glut-1 expression.

PMID- 14962716
TI  - Phase I trial of UFT/leucovorin and irinotecan in patients with advanced cancer.
AB  - UFT (BMS-200604, Uftoral) is an oral fluoropyrimidine that combines uracil and
      the 5-fluorouracil (5-FU) prodrug, ftorafur, in a 4:1 molar ratio with single
      agent activity in breast and gastrointestinal cancers. In vitro studies have
      shown that irinotecan downregulates thymidylate synthase (TS) expression in
      tumour cells, leading to synergy between irinotecan and 5-FU that is maximal when
      irinotecan is given 24 h prior to 5-FU. Given this observed synergy and the
      confirmatory clinical activity of combination therapy with 5-FU, leucovorin (LV)
      and irinotecan, we performed a phase I trial to determine the maximum tolerated
      doses (MTD) of UFT, LV, and irinotecan. Treatment consisted of irinotecan
      administered as a 90-min intravenous (i.v.) infusion on day 1 followed by twice
      daily oral UFT/LV on days 2-15, repeated every 21 days. Initial doses were
      irinotecan 200 mg/m(2) and UFT 200 mg/m(2)/day, with LV dose fixed at 60 mg/day.
      31 patients received a total of 130 cycles of UFT/LV and irinotecan. 3 of 9
      patients experienced grade 3/4 diarrhoea at the highest dose level of irinotecan
      310 mg/m(2) and UFT 300 mg/m(2)/day. Other toxicities included neutropenia,
      anaemia, alopecia, nausea/vomiting and fatigue. Further dose escalation was not
      pursued since this level of toxicity was appropriate for future phase II study.
      One patient with colorectal cancer experienced a partial response and 9 patients
      with non-small cell lung, colorectal and gastro-oesophageal junction carcinomas
      had disease stabilisation lasting 4-26 (median 6) cycles.
      Methylenetetrahydrofolate reductase (MTHFR) C677T genotype was analysed in
      peripheral mononuclear cells (PMNs) obtained from 24 patients. 2 patients had the
      homozygous TT polymorphism and 1 of them had grade 3 diarrhoea at the first dose
      level. Irinotecan on day 1 followed by a 14-day course of oral UFT/LV beginning
      on day 2 is well tolerated, and suitable for testing in several tumour types.
      Doses recommended for further study on this schedule are irinotecan 310 mg/m(2)
      and UFT 300 mg/m(2)/day, with LV 60 mg/day.

PMID- 14962717
TI  - The doxorubicin-streptozotocin combination for the treatment of advanced well
      differentiated pancreatic endocrine carcinoma; a judicious option?
AB  - Due to their rarity, only few trials have studied the role of the doxorubicin
      streptozotocin (DS) combination in advanced well-differentiated pancreatic
      endocrine carcinomas (AWDPEC). However, the published results are inconsistent.
      We reviewed all AWDPEC (5-year period, 45 patients) treated in our institution
      with the DS combination for: objective response rate (ORR), progression-free
      survival, overall survival (OS) and toxicity. An ORR of 36% (95% Confidence
      Interval (CI) 22-49) was obtained, with 16 partial responses (PR). The mean
      duration of PR was of 19.7 months. Two and 3-year OS rates were 50.2 and 24.4%,
      respectively. Toxicities were mainly digestive (grade > or =3 vomiting, 13%) and
      haematological (grade > or =3 neutropenia, 24%). Previous systemic chemotherapy
      and malignant hepatomegaly were associated with a poorer ORR (P=0.033, P=0.016)
      and OS (P=0.008, P=0.045). Multivariate analysis demonstrated previous
      chemotherapy as the only independent predictive-factor for survival (P=0.013). In
      conclusion, our data confirm the sensitivity of AWDPEC to the DS combination,
      with an ORR of 36% and a remarkable median response duration of 19.7 months, and
      suggests that it could be considered as a valid option in first-line therapy.

PMID- 14962718
TI  - Patient preference for either the EORTC QLQ-C30 or the FACIT Quality Of Life
      (QOL) measures: a study performed in patients suffering from carcinoma of an
      unknown primary site (CUP).
AB  - The objective of this study was to examine and compare two core measures of
      Quality Of Life (QOL) used in cancer clinical trials: the European Organisation
      for Research and Treatment of Cancer QOL Core Questionnaire 30 (EORTC QLQ-30) and
      the Functional Assessment of Chronic Illness Therapy (FACIT), in order to
      identify which one patients have the strongest preference for using. 68 patients
      suffering from Carcinomas of an Unknown Primary site (CUP) were recruited in a
      multicentric study; all of them completed both questionnaires, administered in a
      randomised manner. The criteria were the percentage of preferences, and four
      indicators of acceptability. The results indicated that an equal proportion of
      patients preferred the QLQ-C30 (19%) and FACIT (19%). 54% of patients felt both
      questionnaires were acceptable. All the indicators of acceptability favoured the
      QLQ-C30. Analysis of open-ended questions shed light on the difficulties
      encountered by the patients. As no significant preference was observed for one of
      the questionnaires, the QLQ-C30 was chosen on the basis of its significantly
      better acceptability criteria.

PMID- 14962719
TI  - Knowledge of and attitudes toward complementary and alternative therapies; a
      national multicentre study of oncology professionals in Norway.
AB  - This study reports on oncology professionals' knowledge and attitude toward
      complementary and alternative medicines (CAM), classified according to their
      primary application as complementary or alternative methods. In June 2002, we
      conducted a national, multicentre survey of 828 Norwegian oncologists, nurses,
      clerks and therapeutic radiographers. A response rate of 61% was achieved. Only a
      few physicians (4%) described their reactions to alternative medicine as positive
      compared with nurses (33%), therapeutic radiographers (32%) and clerks (55%)
      (P<0.0001). Females showed a more positive view than males (33% versus 14%,
      P<0.0001). More participants expressed a positive attitude to complementary
      versus alternative medicines. Most respondents regarded healing by hand or
      prayer, homeopathy, and Iscador (mistletoe) as alternative therapies. In
      contrast, most respondents classified acupuncture, meditation, reflexology,
      music/art-therapy, aromatherapy and massage as complementary therapies. This
      survey demonstrates major differences, by gender as well as oncology health
      profession in views about and the classification of various CAM methods.

PMID- 14962720
TI  - Multicentre, phase II study evaluating capecitabine monotherapy in patients with
      anthracycline- and taxane-pretreated metastatic breast cancer.
AB  - Treating patients with anthracycline- and taxane-pretreated metastatic breast
      cancer (MBC) represents a significant challenge to oncologists. The tumour
      activated oral fluoropyrimidine, capecitabine, is the only treatment approved for
      these patients. Our study evaluated the efficacy, safety and impact on quality of
      life (QOL) of capecitabine in this setting. Patients (n=126) with anthracycline-
      and taxane-pretreated metastatic breast cancer received capecitabine 1250 mg/m(2)
      twice daily, days 1-14, followed by a 7-day rest period. Median time to
      progression was 4.9 months (95% Confidence Interval (CI): 4.0-6.4). Thirty-five
      patients (28%) achieved an objective response (95% CI: 20-36%), including five
      (4%) complete responses. Median overall survival was 15.2 months (95% CI: 13.5
      19.6 months). Capecitabine demonstrated a favourable safety profile, with a low
      incidence of treatment-related grade 3/4 adverse events. The most common adverse
      events were hand-foot syndrome and gastrointestinal effects. QOL assessment
      showed that capecitabine treatment was associated with an increase in mean Global
      Health Score. Capecitabine is active, well tolerated and improves the QOL of
      patients with anthracycline- and taxane-pretreated metastatic breast cancer.
      Based on the consistently high activity demonstrated in clinical trials,
      capecitabine has become the reference treatment in this setting.

PMID- 14962721
TI  - Current soft-tissue sarcoma classifications.
AB  - In order to analyse the impact of modern sarcoma classification criteria,
      pathological material from 281 extremity soft-tissue sarcomas (STS) was reviewed.
      The cases were originally diagnosed between 1972 and 1994, and the most frequent
      diagnoses then were malignant fibrous histiocytoma (MFH) (26%), liposarcoma
      (21%), fibrosarcoma (11%), and leiomyosarcoma (10%). After reclassification, the
      proportions had changed significantly, with the largest group now being
      leiomyosarcomas (20%), liposarcomas (17%), synovial sarcomas (14%), and sarcomas
      "not otherwise specified" (NOS) (11%). The original diagnosis was changed in 57%
      of the cases; in particular, the number of fibrosarcomas was reduced from 32 to
      6, and MFHs from 72 to 2, with 22 renamed as myxofibrosarcomas; 20 (7%) were
      found not to be sarcomas. The main reasons for these results are the recent
      advances in immunohistochemistry (IHC) together with changes in nomenclature. The
      findings have obvious implications, in particular for retrospective research.

PMID- 14962722
TI  - Surgical treatment of pancreatic adenocarcinoma; actual survival and prognostic
      factors in 343 patients.
AB  - Survival data of patients with pancreatic carcinoma are often overestimated
      because of incomplete follow-up. Therefore, the aim of this study was to approach
      complete follow-up and to analyse survival and prognostic factors of patients who
      underwent surgical treatment for pancreatic adenocarcinoma. Between 1992 and
      2002, 343 patients underwent surgical treatment for pancreatic adenocarcinoma.
      One hundred and sixty patients underwent a resection with a curative intention
      and 183 patients underwent bypass surgery for palliation. Follow-up was complete
      for 93% of patients. Median survival after resection and bypass was 17.0 and 7.5
      months, and 5-year survival was 8% and 0, respectively. In multivariate analysis,
      tumour-positive lymph nodes, non-radical surgery, poor tumour differentiation,
      and tumour size were independent prognostic factors for survival after resection.
      For patients treated with bypass surgery, metastatic disease and tumour size
      independently predicted survival. In conclusion, actual survival of patients with
      pancreatic adenocarcinoma is disappointing compared with the actuarial survival
      rates reported in the literature. The independent prognostic factors for survival
      of patients who underwent surgical treatment for pancreatic adenocarcinoma are
      tumour-related.

PMID- 14962723
TI  - Endoscopic ultrasound-guided fine-needle aspiration in patients with mediastinal
      abnormalities and previous extrathoracic malignancy.
AB  - Enlarged mediastinal lymph nodes in patients with previous extrathoracic
      malignancy require pathological verification. However, surgical procedures lead
      to morbidity and (rarely) mortality. Endoscopic ultrasound with fine-needle
      aspiration (EUS-FNA) is a minimally invasive, outpatient procedure. We
      prospectively assessed its usefulness in patients with mediastinal abnormalities
      and previous extrathoracic malignancy. All patients underwent EUS-FNA prior to
      planned surgical procedures. Specimens were categorised as positive, negative, or
      inconclusive. Surgical procedures were cancelled after positive EUS-FNA. Twenty
      patients underwent EUS-FNA, being positive in eleven and providing an alternative
      diagnosis in one patient (a total of 60%). In 8 patients, EUS-FNA was negative or
      inconclusive, while surgery was positive in five and negative in three.
      Sensitivity and specificity of EUS-FNA were 69 and 100%, respectively. EUS-FNA is
      useful in the assessment of mediastinal abnormalities in patients with previous
      extrathoracic malignancy. Surgical diagnostic procedures were precluded in 60% of
      such patients.

PMID- 14962724
TI  - Phase IB and pharmacological study of the novel taxane BMS-184476 in combination
      with doxorubicin.
AB  - The aim of this study was to define the maximum tolerated dose (MTD) and the
      pharmacological profile of the paclitaxel analogue BMS-184476 given once every 3
      weeks, or on days 1 and 8 every 3 weeks (d1&8), in combination with a fixed dose
      of 50 mg/m(2) of Doxorubicin (Doxo) administered on day 1 of a 21-day cycle.
      Adult patients with advanced solid malignancies received escalating doses of BMS
      184476 infused over 1 h after bolus Doxo. Pharmacokinetics (PK) of BMS-184476,
      Doxo and metabolites were investigated. The effect of BMS-184476 on doxorubicinol
      formation was studied in the cytosol from human myocardium. The MTD of 3-weekly
      BMS-184476 was 30 mg/m(2). The MTD/recommended Phase II dose was 35 mg/m(2)/week
      (70 mg/m(2) per cycle) in the d1&8 schedule. The dose-limiting toxicity was
      neutropenia for both schedules. Other toxicities were loss of appetite, asthenia,
      and mild, cumulative peripheral neuropathy. The objective response rate in 17
      previously untreated or minimally pretreated patients with breast cancer treated
      at 35 mg/m(2)/week of BMS-184476 was 59% (95% Confidence Interval (CI): 33-82%).
      Two of the 7 patients not responding to the study regimen later responded to Doxo
      and paclitaxel. Plasma disposition of BMS-184476 at 30, 35 and 40 mg/m(2) was
      linear without evidence of a PK interaction with Doxo. In studies with cytosol
      from human myocardium, the formation of cardiotoxic doxorubicinol was not
      enhanced by BMS-184476. Dosing of BMS-184476 for 2 consecutive weeks allowed the
      administration of larger doses of the taxane with a promising antitumour activity
      in patients with untreated or minimally pretreated breast cancer. The higher than
      expected myelotoxicity of the 3-weekly schedule is unexplained by the
      investigated interactions. Lack of enhanced doxorubicinol formation in human
      myocardium is consistent with the cardiac safety of the regimen.

PMID- 14962725
TI  - Severity of enterocolitis is predicted by IL-8 in paediatric oncology patients.
AB  - Enterocolitis in oncology patients remains an important complication, but there
      is a lack of insight into its likely severity from microbial, pathological and
      inflammatory aspects. Paediatric oncology patients admitted with neutropenic
      fever, who developed abdominal pain and diarrhoea, were monitored by the takers
      of rectal biopsies, cultures, and inflammatory marker measurements. Twenty-five
      patients were included (mean age 7.1 years). 8 patients (32%) needed intensive
      care treatment, 3 (12%) patients died. Gram-positive bacteraemia was diagnosed in
      4 patients (16%). Most patients had negative blood and stool cultures. Predictors
      of a severe clinical course of the enterocolitis were an increased serum
      interleukin-8 (IL-8) (>1000 pg/ml) level and an increased serum C-reactive
      protein level (CRP) (>150 mg/l) level, both measured on the first day of clinical
      illness. Relative risks (RR) for admission to an Intensive Care Unit (ICU) were
      11.3 (95% Confidence Interval (CI) 1.6-77.9) for elevated IL-8 levels and 6.4
      (95% (CI) 0.92-45.1) for increased CRP levels. Rectal biopsies and pathology
      could not predict outcome (P=0.22). IL-8 analysis at the onset of enterocolitis
      symptoms can identify high-risk patients, which might be used clinically to
      design future intervention trials.

PMID- 14962726
TI  - Medically recorded allergies and the risk of childhood acute lymphoblastic
      leukaemia.
AB  - Data on five allergic conditions were abstracted from the medical records of 180
      cases of childhood acute lymphoblastic leukaemia (ALL) and 718 matched controls.
      Odds Ratios (OR) and 95% Confidence Intervals (CI) were estimated for composite
      variables and for individual allergies using conditional logistic regression
      modelling. Allergies were divided into late and early diagnoses (those made
      within the year before the matched case's ALL diagnosis and those made earlier,
      respectively). Among the early diagnoses, atopy or hives was significantly
      associated with ALL (OR=2.20; 95% CI: 1.16-4.16). Significant associations were
      found for late diagnoses of atopy or hives (OR=3.78; 95% CI: 1.00-14.29) and of
      asthma (OR=3.10; 95% CI: 1.39-6.95). None of the other allergic conditions were
      associated with ALL. These results are contrary to those of prior studies of
      childhood ALL and allergy.

PMID- 14962727
TI  - Little or no space-time clustering found amongst cases of childhood lymphoma in
      North West England.
AB  - We have examined space-time clustering amongst cases of lymphoma in children,
      aged 0-14 years, using population-based data from the North West of England for
      the period 1954-2001. There was little or no evidence for space-time clustering
      amongst all the lymphomas or amongst those sub-groups identified in advance.

PMID- 14962728
TI  - Contraceptive methods and induced abortions and their association with the risk
      of colon cancer in Shanghai, China.
AB  - 267400 female textile workers in Shanghai, who were administered a questionnaire
      at enrollment into a randomised trial of breast self-examination between October
      1989 and October 1991, were followed up until the middle of 2000. Based on the
      655 women who developed colon cancer, rate ratios (RRs) were estimated and trends
      in risk assessed using Cox Proportional Hazards Models. Risk was increased in
      women who used oral contraceptives for over 3 years (RR=1.56, 95% Confidence
      Interval (CI) 1.01-2.40). A possible increase in risk was also observed in women
      who received progestational injections during pregnancy (RR=1.24, 95% CI 0.95
      1.62), but not in relation to the use of injectable contraceptives. A possible
      reduction in risk was associated with tubal ligation (RR=0.86, 95% CI 0.71-1.03)
      and ever having had an induced abortion (RR=0.84, 95% CI 0.71-1.00). No trends in
      risk were observed in relation to the duration of hormonal contraceptive use or
      the number of induced abortions. Additional studies of the possible roles
      contraceptives may play in the aetiology of colon cancer in women at low risk of
      this disease are warranted.

PMID- 14962729
TI  - Inhibition of P-glycoprotein function by XR9576 in a solid tumour model can
      restore anticancer drug efficacy.
AB  - Resistance to cancer chemotherapy involves both altered drug activity at the
      designated target and modified intra-tumour pharmacokinetic properties (e.g.
      uptake, metabolism). The membrane transporter P-glycoprotein (P-gp) plays a major
      role in pharmacokinetic resistance by preventing sufficient intracellular
      accumulation of several anticancer agents. Whilst inhibiting P-gp has great
      potential to restore chemotherapeutic effectiveness in blood-borne cancers, the
      situation in solid tumours is less clear. Therefore, the degree of resistance
      tumours pose to the cytotoxicity of vinblastine and doxorubicin was characterised
      using the multicellular tumour spheroid model. Tumour spheroids were generated
      from either drug-sensitive MCF7(WT) breast cancer cells or a resistant P-gp
      expressing variant (NCI/ADR(Res)). Drug-induced cytotoxicity in tumour spheroids
      was measured using an outgrowth assay and compared with that observed in
      monolayer cultures. As anticipated, the 3-D organisation of MCF7(WT) in tumour
      spheroids was associated with a reduction in the potency of doxorubicin and
      vinblastine-i.e. the inherent multicellular resistance phenomenon. In contrast,
      tumour spheroids from NCI/ADR(Res) cells did not display multicellular
      resistance. However their constitutive expression of P-gp reduced the potency of
      both anticancer drugs. Moreover, the highly potent P-gp inhibitor, the
      anthranilic acid derivative, XR9576, was able to restore the cytotoxic efficacy
      of both drugs in tumour spheroids comprising NCI/ADR(Res) cells. The results
      suggest that inhibition of P-gp in solid tumours is achievable and that
      generation of potent inhibitors will provide a significant benefit towards
      restoration of chemotherapy in solid tissues.

PMID- 14962730
TI  - Inhibition of multidrug resistance by immunisation with synthetic P-glycoprotein
      derived peptides.
AB  - Overexpression of the membrane glycoprotein (P170) represents the most common
      multidrug resistance (MDR) mechanism in cancer therapy. Specific auto-antibodies
      to extracellular loops 1, 2 and 4 of murine P170 were elicited in mice using
      palmitoylated synthetic peptides reconstituted in liposomes, with or without
      Lipid A, and resuspended in alum. IgM antibodies were detected 14 days following
      the first injection and IgG1 became predominant after the third challenge.
      Animals did not show any auto-immune symptoms or induced toxicity up to 18 months
      after the immunisation. Previous immunisations of mice using liposomes with MDR1
      peptides increases the efficacy of chemotherapy treatments with doxorubicin and
      vinblastine against P388 R cells with increase of 77% in the survival half time
      in the immunised group. Sera from the immunised mice were also effective in
      reducing cellular resistance to vinblastine and doxorubicin in vitro. Taken
      together, these data suggest that this immunisation approach might have potential
      clinical applications.

PMID- 14962731
TI  - PGP9.5 mRNA could contribute to the molecular-based diagnosis of medullary
      thyroid carcinoma.
AB  - The protein gene product 9.5 (PGP9.5) is a ubiquitin hydrolase that is widely
      expressed in neuronal tissues at all stages of neuronal differentiation and is a
      known neuroendocrine marker. Medullary thyroid carcinoma (MTC) arises from
      parafollicular cells and is reported to overexpress several mRNAs such as RET,
      calcitonin, and CEA. These markers are thought to be useful in determining a
      molecular-based diagnosis of MTC. We examined the expression levels of PGP9.5
      mRNA in 80 thyroid tissues using real-time quantitative reverse transcription (RT
      PCR) and found that PGP9.5 mRNA was overexpressed in all 11 MTCs examined, both
      hereditary and sporadic, but not in other histological tumour types. Furthermore,
      by RT-PCR, PGP9.5 mRNA was detected only in aspirates from three medullary
      carcinomas, and not in aspirates from other tumour types. These results
      demonstrate that, in addition to the expression of RET, calcitonin and CEA,
      PGP9.5 mRNA expression may contribute to the molecular-based diagnosis of MTCs.

PMID- 14962732
TI  - Comment on "The process of metastasisation for breast cancer" by J. Engel, R.
      Eckel, J. Kerr et al.

PMID- 14962734
TI  - Where to next with extracranial rhabdoid tumours in children.

PMID- 14962735
TI  - Involvement of beta(1) integrin in betaAP-induced apoptosis in human
      neuroblastoma cells.
AB  - Integrin-mediated cell adhesion is required for cell survival and
      differentiation. Recently, integrins have been proposed as a target for beta
      amyloid peptide (betaAP) neurotoxicity. We report here that treatment with betaAP
      (1-42) or with the active betaAP fragment (25-35) induced a great deal of
      apoptosis in SK-N-BE and SH-SY5Y cell lines. In the presence of either collagen I
      degrees, fibronectin, or laminin, betaAP toxicity was severely reduced. This
      protective effect seems to be mediated by integrins, because preincubation of
      neuroblastoma cells with antibodies directed against beta(1) and alpha(1)
      integrin subunits greatly enhanced betaAP-induced apoptosis. In addition,
      treatment with betaAP induced a strong reduction of beta(1) and alpha(1) integrin
      subunits expressed in plasma membrane, which occurred 3 h after treatment, before
      the appearance of the apoptotic morphology. The rapid downregulation of the
      alpha(1)beta(1) integrin was almost completely recovered 15-24 h after betaAP
      treatment and was not prevented by cycloheximide. In conclusion, our data
      indicate a relationship between betaAP neurotoxicity and modulation of
      alpha(1)beta(1) integrin expression, and support the hypothesis that aberrant
      integrin function may play a significant role in betaAP-mediated neurotoxicity.

PMID- 14962736
TI  - Neuronal vulnerability following inhibition of mitochondrial complex II: a
      possible ionic mechanism for Huntington's disease.
AB  - An impaired complex II (succinate dehydrogenase, SD) striatal mitochondrial
      activity is one of the prominent metabolic alterations in Huntington's disease
      (HD), and intoxication with 3-nitropropionic acid (3-NP), an inhibitor of
      mitochondrial complex II, mimics the motor abnormalities and the pathology of HD.
      We found that striatal spiny neurons responded to this toxin with an irreversible
      membrane depolarization/inward current, while cholinergic interneurons showed a
      hyperpolarization/outward current. Both these currents were sensitive to
      intracellular concentration of ATP. The 3-NP-induced depolarization was
      associated with an increased release of endogenous GABA, while acetylcholine
      levels were reduced. Moreover, 3-NP induced a higher depolarization in
      presymptomatic R6/2 HD transgenic mice compared to wild-type (WT) mice, showing
      an increased susceptibility to SD inhibition. Conversely, the hyperpolarization
      did not significantly differ from the one recorded in WT mice. The diverse
      membrane changes induced by SD inhibition may contribute to the cell-type
      specific neuronal death in HD.

PMID- 14962737
TI  - Fibroblast growth factor receptor 3 signaling regulates injury-related effects in
      the peripheral nervous system.
AB  - Fibroblast growth factor receptor (FGFR) signaling is crucial for neural
      development and regeneration. Here we investigated the L5 spinal ganglion and the
      sciatic nerve of intact Fgfr3-deficient mice after nerve injury. Quantification
      of sensory neurons in the L5 spinal ganglion revealed no significant differences
      between wild-type and Fgfr3-deficient mice. Seven days after nerve lesion, the
      normally occurring neuron loss in wild-type mice was not found in Fgfr3-deficient
      animals, suggesting that FGFR3 signaling is involved in the cell death process.
      Morphometric analysis of the sciatic nerve showed similar numbers of myelinated
      axons, but the axonal and myelin diameter was significantly smaller in Fgfr3
      deficient mice compared to the wild types. Evaluation of regenerating myelinated
      axons of the sciatic nerve revealed no differences between both mouse strains 7
      days after crush injury. Our results suggest that FGFR3 signaling seems to be
      involved in processes of damage-induced neuron death and axonal development.

PMID- 14962738
TI  - The trunk neural crest and its early glial derivatives: a study of survival
      responses, developmental schedules and autocrine mechanisms.
AB  - Regulation of survival during gliogenesis from the trunk neural crest is poorly
      understood. Using adapted survival assays, we directly compared crest cells and
      the crest-derived precursor populations that generate satellite cells and Schwann
      cells. A range of factors that supports Schwann cells and glial precursors does
      not rescue crest, with the major exception of neuregulin-1 that rescues crest
      cells provided they contact the extracellular matrix. Autocrine survival appears
      earlier in developing satellite cells than Schwann cells. Satellite cells also
      show early expression of S100beta, BFABP and fibronectin and early survival
      responses to IGF-1, NT-3 and PDGF-BB that in developing Schwann cells are not
      seen until the precursor/Schwann cell transition. These experiments define novel
      differences between crest cells and early glia and show that entry to the glial
      lineage is an important point for regulation of survival responses. They show
      that survival mechanisms among PNS glia differ early in development and that
      satellite cell development runs ahead of schedule compared to Schwann cells in
      several significant features.

PMID- 14962739
TI  - Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated
      protein complex: implications for schizophrenia and other major neurological
      disorders.
AB  - Disrupted In Schizophrenia 1 (DISC1) was identified as a potential susceptibility
      gene for schizophrenia due to its disruption by a balanced t(1;11) (q42;q14)
      translocation, which has been shown to cosegregate with major psychiatric disease
      in a large Scottish family. We have demonstrated that DISC1 exists in a
      neurodevelopmentally regulated protein complex with Nudel. The complex is
      abundant at E17 and in early postnatal life but is greatly reduced in the adult.
      Nudel has previously been shown to bind Lis1, a gene underlying lissencephaly in
      humans. Critically, we show that the predicted peptide product resulting from the
      Scottish translocation removes the interaction domain for Nudel. DISC1 interacts
      with Nudel through a leucine zipper domain and binds to a novel DISC1-interaction
      domain on Nudel, which is independent from the Lis1 binding site. We show that
      Nudel is able to act as a bridge between DISC1 and Lis1 to allow formation of a
      trimolecular complex. Nudel has been implicated to play a role in neuronal
      migration, together with the developmental variation in the abundance of the
      DISC1-Nudel complex, may implicate a defective DISC1-Nudel complex as a
      neurodevelopmental cause of schizophrenia.

PMID- 14962740
TI  - EphA/ephrin-A interactions during optic nerve regeneration: restoration of
      topography and regulation of ephrin-A2 expression.
AB  - During visual system development, interactions between Eph tyrosine kinase
      receptors and their ligands, the ephrins, guide retinal ganglion cell (RGC) axons
      to their topographic targets in the optic tectum. Here we show that Eph/ephrin
      interactions are also involved in restoring topography during RGC axon
      regeneration in goldfish. Following optic nerve crush, EphA/ephrin-A interactions
      were blocked by intracranial injections of recombinant Eph receptor (EphA3-AP) or
      phospho-inositol phospholipase-C. Topographic errors with multiple inputs to some
      tectal loci were detected electrophysiologically and increased projections to
      caudal tectum demonstrated by RT-97 immunohistochemistry. In EphA3-AP-injected
      fish, ephrin-A2-expressing cells in the retino-recipient tectal layers were
      reduced in number compared to controls and their distribution was no longer
      graded. The findings, supported by in vitro studies, implicate EphA/ephrin-A
      interactions in restoring precise topography and in regulating ephrin-A2
      expression during regeneration.

PMID- 14962741
TI  - Neuronal gelsolin prevents apoptosis by enhancing actin depolymerization.
AB  - Gelsolin (gsn), an actin-severing protein, protects neurons from excitotoxic cell
      death via inactivation of membranous Ca(2+) channels. Its role during apoptotic
      cell death, however, has remained unclear. Using several models of neuronal cell
      death, we demonstrate that endogenous gelsolin has anti-apoptotic properties that
      correlate to its dynamic actions on the cytoskeleton. We show that neurons
      lacking gelsolin (gsn(-/-)) have enhanced apoptosis following exposure to
      staurosporine, thapsigargin, or the cholinergic toxin ethylcholine aziridinium
      (AF64A). AF64A-induced loss of mitochondrial membrane potential and activation of
      caspase-3 was specifically enhanced in gsn(-/-) neurons and could be reversed by
      pharmacological inhibition of mitochondrial permeability transition. Moreover,
      increased caspase-3 activation and cell death in AF64A-treated gsn(-/-) neurons
      were completely reversed by pharmacological depolymerization of actin filaments
      and further enhanced by their stabilization. In conclusion, actin remodeling by
      endogenous gelsolin or analogues protects neurons from apoptosis mediated by
      mitochondria and caspase-3.

PMID- 14962742
TI  - Altered expression of ion channel isoforms at the node of Ranvier in P0-deficient
      myelin mutants.
AB  - To elucidate the impact of myelinating Schwann cells on the molecular
      architecture of the node of Ranvier, we investigated the nodal expression of
      voltage-gated sodium channel (VGSC) isoforms and the localization of paranodal
      and juxtaparanodal membrane proteins in a severely affected Schwann cell mutant,
      the mouse deficient in myelin protein zero (P0). The abnormal myelin formation
      and compaction was associated with immature nodal cluster types of VGSC. Most
      strikingly, P0-deficient motor nerves displayed an ectopic nodal expression of
      the Na(v)1.8 isoform, where it is coexpressed with the ubiquitous Na(v)1.6
      channel. Furthermore, Caspr was distributed asymmetrically or was even absent in
      the mutant nerve fibers. The potassium channel K(v)1.2 and Caspr2 were not
      confined to juxtaparanodes, but often protruding into the paranodes. Thus,
      deficiency of P0 leads to dysregulation of nodal VGSC isoforms and to altered
      localization of paranodal and juxtaparanodal components of the nodal complex.

PMID- 14962743
TI  - Humanin rescues cortical neurons from prion-peptide-induced apoptosis.
AB  - We recently demonstrated that a soluble oligomeric prion peptide, the putative
      118-135 transmembrane domain of prion protein (PrP), exhibited membrane fusogenic
      properties and induced apoptotic cell death both in vitro and in vivo. A recently
      discovered rescue factor humanin (HN) was shown to protect neuronal cells from
      various insults involved in human neurodegenerative diseases. We thus addressed
      the question of whether HN might modulate the apoptosis induced by the soluble
      PrP(118-135) fragment. We found that the incubation of rat cortical neurons with
      10 microM HN prevented soluble PrP(118-135) fragment-induced cell death
      concomitantly with inhibition of apoptotic events. An HN variant, termed HNG,
      exhibited a 500-fold increase in the protective activity in cortical neurons,
      whereas the HNA variant displayed no protective effect. The effects of HN and HNG
      peptides did not require a preincubation with the PrP(118-135) fragment, strongly
      suggesting that these peptides rescue cells independently of a direct interaction
      with the prion peptide. By contrast, and in agreement with a previous study, HN
      had no effect on the fibrillar PrP(106-126) peptide-induced cell death. This
      protective effect for neurons from PrP(118-135)-induced cell death strongly
      suggests that PrP(118-135) and PrP(106-126) peptides may trigger different
      pathways leading to neuronal apoptosis.

PMID- 14962744
TI  - Improvement of neuronal visual responses in the superior colliculus in
      Prph2(Rd2/Rd2) mice following gene therapy.
AB  - Inherited retinal degenerations are a major cause of blindness for which there
      are currently no effective therapies. Significant progress concerning in vivo
      gene transfer has allowed retardation of degeneration or retinal functional
      improvement in different animal models. To date, there has been no evaluation of
      the impact of these treatments on higher visual function, a critical step for
      validating gene therapy treatment strategies. Here, we have used adeno-associated
      (AAV2)-mediated gene transfer of Prph2 in the Prph2(Rd2/Rd2) mouse model. We then
      assessed higher visual function by recording from central visually responsive
      neurons in the superior colliculus and improvements were correlated in individual
      animals with retinal function (ERG) and histological and biochemical changes.
      Although gene replacement therapy only partially restores photoreceptor
      morphology, it results in a 300% increase of the visual cycle protein rhodopsin,
      leading to retinal function improvement (250% increase of b-wave amplitude) and
      significantly higher central visual responses (166% increase at 24 cd/m(2)).
      These findings suggest that gene replacement therapy leading to even relatively
      modest structural improvement may result in improved central visual function.

PMID- 14962745
TI  - Myelin transcription factor 1 (Myt1) modulates the proliferation and
      differentiation of oligodendrocyte lineage cells.
AB  - Myelin transcription factor 1 (Myt1) is a zinc finger DNA-binding protein that is
      expressed in neural progenitors and oligodendrocyte lineage cells. This study
      examines the role of Myt1 in oligodendrocyte lineage cells by overexpressing
      putative functional domains, a four-zinc finger DNA-binding region (4FMyt1) or a
      central protein-protein interaction domain (CDMyt1), without the predicted
      transcriptional activation domain. In the presence of mitogens, overexpression of
      4FMyt1 inhibited proliferation of oligodendrocyte progenitors, but not cell types
      (astrocytes and NIH3T3 cells) lacking endogenous Myt1. Expression of 4FMyt1
      inhibited the differentiation of oligodendrocyte progenitors into
      oligodendrocytes as assessed by morphology, immunostaining, and myelin gene
      expression. Progenitor differentiation was similarly inhibited by expression of
      CDMyt1 but only partially suppressed by overexpression of the intact Myt1. These
      data indicate that Myt1 may regulate a critical transition point in
      oligodendrocyte lineage development by modulating oligodendrocyte progenitor
      proliferation relative to terminal differentiation and up-regulation of myelin
      gene transcription.

PMID- 14962746
TI  - Bimodal induction of dopamine-mediated striatal neurotoxicity is mediated through
      both activation of D1 dopamine receptors and autoxidation.
AB  - Striatal neurodegeneration occurs through unknown mechanisms in certain
      neurodegenerative disorders characterized by increased and sustained synaptic
      levels of dopamine (DA). Treatment of rat primary striatal neurons with DA causes
      profound neurotoxicity, with increased production of free radicals and
      accelerated neuronal death. DA effects were partly reduced by the antioxidant
      sodium metabisulfite (SMBS), and the D1 DA receptor antagonist, SCH 23390, and
      were completely blocked upon co-treatment with SMBS and SCH 23390. Part of DA
      effects were mimicked by either H(2)O(2), or by the D1 agonist, SKF R-38393,
      indicating the existence of two distinct signaling pathways through which the
      neurotoxicity of DA is manifest. DA effects did not proceed through D2-like DA or
      beta-adrenergic receptor signaling pathways. The D1 receptor-mediated and the
      autoxidative pathways of DA neurotoxicity converge to cause activation and/or
      increased synthesis of neuronal and inducible, but not endothelial, nitric oxide
      synthase (NOS). The reduction of DA striatal neurotoxicity through blockade of D1
      DA receptors, suggests novel therapeutic approaches in the management of striatal
      neurodegeneration.

PMID- 14962747
TI  - Cadherins guide migrating Purkinje cells to specific parasagittal domains during
      cerebellar development.
AB  - Several cadherins are expressed in parasagittal Purkinje cell domains, which can
      be defined by their afferent and efferent connectivity in the developing and
      mature cerebellum. By in vivo electroporation in chicken embryos, we demonstrate
      that Purkinje cell progenitors, which overexpress cadherin-6B or cadherin-7,
      distribute preferentially to those Purkinje cell domains, which express the
      respective cadherin endogenously. This differential distribution may be based, at
      least in part, on the guidance of migrating neurons along neurites that express
      the same cadherin. Selective induction of apoptosis and cadherin-based cell
      sorting within cortical domains do not seem to contribute to the differential
      distribution. These results show that cadherins can tell early neurons where to
      integrate in functional brain gray matter, possibly by a cadherin-based homotypic
      adhesive mechanism.

PMID- 14962748
TI  - Defective neuronogenesis in the absence of Dlx5.
AB  - Dlx genes play an important role in the control of the development of the central
      nervous system (CNS). Single or compound inactivation of Dlx1, Dlx2, or Dlx5 in
      the mouse causes defects of neuronal migration and differentiation. Dlx5, in
      particular, is essential for the correct development of the olfactory system.
      Targeted inactivation of Dlx1 and Dlx2 in the mouse results in abnormal neuronal
      differentiation in the embryonic subcortical forebrain and is associated to the
      loss of Dlx5 and Dlx6 expression. So far, however, it has been impossible to
      investigate the role of Dlx genes on late neurogenesis, as their inactivation
      leads to perinatal death. We have now generated cultures of neural stem cells
      (NSCs) derived from embryonic and newborn Dlx5-null mice, and we have compared
      their capacity to differentiate in vitro to that of equivalent cells derived from
      normal littermates. We show here that in the absence of Dlx5, NSCs derived from
      newborn animals have a severely reduced capacity to generate neurons. This is not
      the case for cells derived from E12.5 embryos. Forced expression of Dlx5 in
      cultures of newborn mutant NSCs fully restores their neuronogenic potential. Our
      data suggest that Dlx5 is essential for secondary (postnatal) neuronogenesis.

PMID- 14962749
TI  - Modulation of zinc toxicity by tissue plasminogen activator.
AB  - The tissue plasminogen activator (tPA)-plasmin proteolytic system mediates
      excitotoxin-induced neurodegeneration in vivo and in cell culture. tPA also
      confers neuroprotection from zinc toxicity in cell culture through a proteolysis
      independent mechanism. This raises two questions: what is this non-enzymatic
      mechanism, and why tPA does not synergize with zinc to promote neuronal cell
      death? We show here that zinc binds to tPA and inhibits its activity in a dose
      dependent fashion, thus terminating its protease-dependent neurotoxic capacity.
      We extend the previously reported culture findings to demonstrate that elevated
      zinc is neurotoxic in vivo, and even more so when tPA is absent. Thus,
      physiological levels of tPA confer protection from elevated free zinc.
      Mechanistically, tPA promotes movement of zinc into hippocampal neuron cells
      through voltage-sensitive Ca(2+) channels and Ca(2+)-permeable AMPA/KA channels.
      Therefore, zinc and tPA each appear to be able to limit the potential of the
      other to facilitate neurodegeneration, a reciprocal set of actions that may be
      critical in the hippocampus where tPA is secreted during the nonpathological
      conditions of learning and memory at sites known to be repositories of free and
      sequestered zinc.

PMID- 14962750
TI  - Differential role of poly(ADP-ribose) polymerase-1in apoptotic and necrotic
      neuronal death induced by mild or intense NMDA exposure in vitro.
AB  - Overactivation of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1) plays
      a key role in the mechanisms responsible for neuronal death. In the present
      study, we examined the effects of the PARP-1 inhibitor 3,4-dihydro-5-[4-1(1
      piperidinyl)buthoxy]-1(2H)-isoquinolinone (DPQ) in two models of N-methyl-d
      aspartate (NMDA)-induced neurotoxicity. The exposure of mixed cultured cortical
      cells to 300 microM NMDA for 10 min induced a caspase-dependent type of apoptotic
      neuronal death. Conversely, exposure to 2 mM NMDA for 10 min led to the
      appearance of morphological features of necrosis, with no increase in caspase-3
      activity and depletion in adenosine triphosphate (ATP) levels. DPQ (10 microM)
      reduced the NMDA-induced PARP activation, restored ATP to near control levels and
      significantly attenuated neuronal injury only in the severe NMDA exposure model.
      Similar results were obtained when pure neuronal cortical cultures were used.
      PARP-1 activation thus appears to play a preferential role in necrotic than in
      caspase-dependent apoptotic neuronal death.

PMID- 14962751
TI  - Astrocytic regulation of NMDA receptor subunit composition modulates the toxicity
      of prion peptide PrP106-126.
AB  - Prion diseases are neurodegenerative conditions. The main pathological
      alterations common to these diseases include the loss of neurones, gliosis and
      the deposition of an abnormal isoform of the prion protein in aggregates in the
      nervous tissue. Prevention of the devastating effects of prion disease requires
      prevention of neuronal death. Therefore, understanding the mechanism by which
      this occurs is essential. Cell culture studies using the synthetic peptide PrP106
      126 have been central to developing a model of this mechanism. Using a coculture
      system, we have shown that PrP106-126 caused neuronal death mediated by
      glutamate. This neuronal death resulted from modification of the expression of
      NMDA receptor subtypes stimulated by the exposure of neurones to the combination
      of astrocytic factors, elevated Cu and PrP106-126. The results of these
      experiments suggest neuronal death in prion disease might be reduced by the use
      of NMDA receptor antagonists such as MK801 or inhibitors of the arachidonic acid
      metabolism pathway.

PMID- 14962752
TI  - Recombinant allergens: from production and characterization to diagnosis,
      treatment, and prevention of allergy.

PMID- 14962753
TI  - Recombinant allergens in the US.
AB  - Recombinant allergens may increase the safety and efficacy of allergen
      immunodiagnostics and immunotherapy, and may prove to be excellent tools for the
      standardization of existing, natural allergens. However, there are several
      biological and regulatory issues that need to be addressed as these products are
      moved from bench to bedside. This article discusses some of these issues.

PMID- 14962754
TI  - Cloning allergens via phage display.
AB  - Although an impressive list of allergenic structures has been elucidated during
      the last decade by classical cloning methods, the size of the repertoire of
      molecular structures able to elicit allergic reactions is still unknown.
      Selective enrichment of cDNA libraries displayed on phage surface with serum IgE
      from allergic individuals combined with robotic-based high-throughput screening
      technology has proved to be extremely successful for the rapid isolation of
      allergens. The basic concept of linking the phenotype, expressed as gene product
      displayed on the phage coat, to its genetic information integrated into the phage
      genome, creates fusion proteins covalently associated with the infectious
      particle itself. Therefore, cDNA libraries displayed on phage surface can be
      screened for the presence of specific clones using the discriminative power of
      affinity purification. The selection of IgE-binding clones involves the
      enrichment of phage binding to serum IgE immobilised to a solid phase during
      consecutive rounds of affinity selection. As a consequence of the physical
      linkage between genotype and phenotype, sequencing of the DNA of the integrated
      section of the phage genome can readily elucidate the amino acid sequence of the
      surface-displayed allergen. In spite of some biological limitations imposed by
      Escherichia coli as expression host, phage surface display technology has
      strongly contributed to the rapid isolation of a vast variety of IgE-binding
      structures.

PMID- 14962755
TI  - Lab scale and medium scale production of recombinant allergens in Escherichia
      coli.
AB  - Recombinant products have become invaluable tools for diagnostic as well as
      therapeutic purposes in modern medicine. Especially in cases where raw naturally
      derived products are difficult to standardize, well-defined recombinant single
      components represent the matter of choice. In the recent past, much effort has
      been undertaken to define individual proteins derived from various sources like
      pollen, spores of moulds, pet dander, and food causing Type 1 allergic reactions
      in humans. Therefore, methods for cloning, sequencing, and expressing cDNAs
      coding for allergens in Escherichia coli became of great interest to
      allergologists. For the recombinant production of allergens, suitable expression
      systems, growing conditions, and purification steps have to be established for
      each individual product. Finally, the purified recombinant allergen has to be
      carefully investigated for the biochemical, biophysical, and immunological
      properties. In the following paper, several prokaryotic expression systems,
      purification strategies, and analytical methods will be presented and pitfalls
      discussed.

PMID- 14962756
TI  - Plant virus expression systems for transient production of recombinant allergens
      in Nicotiana benthamiana.
AB  - In recent years, several studies have demonstrated the use of autonomously
      replicating plant viruses as vehicles to express a variety of therapeutic
      molecules of pharmaceutical interest. Plant virus vectors for expression of
      heterologous proteins in plants represent an attractive biotechnological tool to
      complement the conventional production of recombinant proteins in bacterial,
      fungal, or mammalian cells. Virus vectors are advantageous when high levels of
      gene expression are desired within a short time, although the instability of the
      foreign genes in the viral genome may present problems. Similar levels of foreign
      protein production in transgenic plants often are unattainable, in some cases
      because of the toxicity of the foreign protein. Now virus-based vectors are for
      the first time investigated as a means of producing recombinant allergens in
      plants. Several plant virus vectors have been developed for the expression of
      foreign proteins. Here, we describe the utilization of tobacco mosaic virus- and
      potato virus X-based vectors for the transient expression of plant allergens in
      Nicotiana benthamiana plants. One approach involves the inoculation of tobacco
      plants with infectious RNA transcribed in vitro from a cDNA copy of the
      recombinant viral genome. Another approach utilizes the transfection of whole
      plants from wounds inoculated with Agrobacterium tumefaciens containing cDNA
      copies of recombinant plus-sense RNA viruses.

PMID- 14962757
TI  - Over-expression and production of plant allergens by molecular farming
      strategies.
AB  - Recombinant allergens have become a valuable tool for diagnosis and may also be
      used for therapy in the near future. To supply the required large amounts of
      functional recombinant proteins on a cost-effective basis, the production of
      allergens in plants by molecular farming is an alternative to microbial
      expression systems. Especially as post-translational modifications of the
      allergens, e.g., phosphorylation and glycosylation, may be important for
      recognition by the human immune system, the plant-based production of recombinant
      allergens enables the correct folding, glycosylation, and other modifications of
      the recombinant allergen. An introduction to the methods for plant transformation
      via the tumor-inducing bacterium, Agrobacterium tumefaciens, is given in this
      paper.

PMID- 14962758
TI  - Circular dichroism analysis of allergens.
AB  - Recombinant allergens have gained a lot of importance lately for the diagnosis of
      allergic diseases and for specific immunotherapy. To characterize recombinant
      allergens and potential hypo-allergenic derivatives thereof circular dichroism
      (CD) spectroscopy is used widely. It is a convenient, fast method to assess the
      structural integrity of the recombinant proteins, compare them with the allergens
      isolated from natural sources, and to determine the effects of mutations on the
      structural properties. In this paper, we will describe the techniques and the
      most useful applications of CD spectroscopy to the field of allergy research.

PMID- 14962759
TI  - Microarrayed allergens for IgE profiling.
AB  - Diagnosis of type I allergy is based on anamnesis, provocation testing, and
      serological determination of total and specific IgE. Currently, in vivo and in
      vitro diagnostic tests employ allergen extracts prepared from various allergen
      sources (e.g., pollen, mites, animal dander, moulds, foods, venoms, etc.). The
      application of recombinant DNA technology to the field of allergen
      characterization has allowed to reveal the molecular nature of the most common
      allergens. To date a continuously increasing number of allergen sequences has
      become available and panels of recombinant allergens-assembling the epitope
      complexity of natural allergens sources-can be produced. The use of recombinant
      allergens instead of crude, natural extracts for allergy diagnosis allows us to
      determine the individual IgE reactivity profile of each patient. To enable a
      comprehensive analysis of the patient's IgE binding pattern to a large number of
      individual allergens, a new type of serological test is required. In this paper,
      we applied microarray technology to create a multi-allergen test system, based on
      microarrayed recombinant allergens.

PMID- 14962760
TI  - Recombinant allergens for analysing T-cell responses.
AB  - T-cell responses constitute a central element of allergic disease and a model for
      studying Th1 and Th2 cytokine pathways. Most studies to date have used extracts
      of allergens which contain variable quantities of different allergens and non
      allergenic antigens. Recombinant allergens provide the tools for studying the
      responses to allergens in a reproducible and dose-dependent manner and the
      different T-cell responses of allergic and non-allergic subjects provide a method
      for verifying the responses and their relationship to allergic sensitisation.
      Most allergies show dominant responses to one or a few major allergens. These
      allergens have been described for the common allergies and have been produced as
      recombinant allergens. A particular problem for allergens is that many are
      mixtures of proteins from multi-gene families or are highly polymorphic.
      Information now exists so the sequence variation can be represented. Purified
      recombinant allergens produced by standard expression systems stimulate the
      expected T-cell responses from the peripheral blood of allergic and non-allergics
      to allergen extracts. Although stimulation with recombinant allergens which are
      not produced with a natural IgE binding activity can provide a measure of
      allergenicity, the altered tertiary structure can reduce Th2 responses. The
      sequence information now available provides the means to use PCR to produce cDNA
      for the production of recombinant allergens from readily available sources. The
      production of the highly reactive recombinant Der p 2 allergen of house dust mite
      from natural sources is described.

PMID- 14962761
TI  - Assays for measuring in vitro basophil activation induced by recombinant
      allergens.
AB  - The diagnosis of type I allergy is essentially based on clinical data, skin
      tests, and measurements of allergen-specific IgE. However, the determination of
      specific IgE per se does not permit a definitive conclusion concerning the
      response of effector cells to the respective allergen(s) and consecutive clinical
      symptoms in all patients. In an attempt to overcome this problem, a number of
      basophil-activation assays have been developed during the last few years. Today,
      allergen-induced activation of blood basophils can be employed as a specific and
      reliable measure of IgE-dependent responses in sensitized individuals. Using
      recombinant allergens and basophil-specific markers, these novel assays appear to
      serve as simple and useful tests in component-resolved diagnosis of type I
      allergies. In the current article, the biochemical, functional, and technical
      background of these basophil tests is discussed.

PMID- 14962762
TI  - Animal models of type I allergy using recombinant allergens.
AB  - Various animal models including guinea pigs, monkeys, dogs, rats, and mice have
      been established in an attempt to provide insights into the complex immunological
      and pathophysiological mechanisms of human type I allergic diseases. The detailed
      knowledge of the murine genome, the various components of the murine immune
      system, and the generation of engineered mice has made the murine system the most
      attractive among all animal models. The availability of multitude technologies
      and reagents to characterize and manipulate immunological pathways and mediators
      adds to the outstanding opportunities to assess the pathology of allergic
      diseases and to develop novel therapeutic strategies in mice. Numerous
      sensitization protocols with food and aero-allergens are used to establish an
      allergic/asthma-like phenotype in mice. Requirements for an appropriate murine
      model include a close resemblance to the pathology of the disease in humans, the
      objective measurement of the physiologic parameters, as well as reliability and
      reproducibility of the experimental data. With respect to reproducible
      experimental conditions, it has been recognized that extract preparations from
      natural allergen sources can vary in their allergen-content and -composition.
      This might influence the degree of sensitization or the outcome of treatment
      strategies in dependence of the applied extract preparation. The use of
      recombinant allergens in experimental in vivo and in vitro systems can overcome
      these problems. Another aspect, that has become obvious from the experimental
      studies, is that allergens can differ in their immunogenicity as well as in their
      capacity to act as tolerogens. Therefore, it seems important that the efficacy of
      the different allergen-molecules to act as therapeutic agents is individually
      examined. In this review, examples of animal models are described, in which
      recombinant allergens have been used for sensitization and/or treatment of
      allergic responses and how they have been used to enhance our understanding of
      the pathology of allergic diseases.

PMID- 14962763
TI  - Provocation testing with recombinant allergens.
AB  - In the past few decades, DNA technology has enabled the production of defined
      recombinant allergen molecules for diagnostic and therapeutic purposes.
      Recombinant allergens containing most of the relevant IgE epitopes present in
      natural allergen sources are now available and allergen proteins can be produced
      that are identical, without biological or batch-to-batch variation. A great
      advantage of recombinant allergens is that they can be used for component
      resolved diagnostics, which makes it possible to establish the patient's
      individual IgE reactivity profile before therapy is selected. However, before
      recombinant allergens can be applied in clinical practice their biological
      activity has to be carefully investigated in vivo. We here describe the most
      commonly used provocation methods (skin tests (prick and intradermal), nasal,
      bronchial, and conjunctival provocations) and how they can be performed. We also
      discuss the results so far obtained with in vivo testing using recombinant
      allergens and envisage their future use for immunotherapy.

PMID- 14962764
TI  - Improving diagnostic tests for food allergy with recombinant allergens.
AB  - Food allergy is one important manifestation of atopic allergy. Primary food
      allergy mainly affects young children (class I), whereas adults frequently
      develop food allergy as a consequence of an inhalant sensitization (class II). At
      present, the diagnostic instrument for proving class II food allergy is not
      satisfactory. Skin tests as well as serological tests are in general neither very
      specific nor highly sensitive because they depend on food extracts, which differ
      in their content of individual allergens, vary between manufacturers, and even
      between different batches. Since the presence of food allergen-specific IgE
      antibodies does not always correlate with clinical symptoms against the
      respective food, oral provocation tests (ideally double-blind placebo-controlled
      food challenges) have to be performed to validate serological diagnosis or skin
      tests. However, oral provocation tests are connected to several practical
      problems and include a specific risk for the allergic patient. Applying DNA
      technology, up to 40 food allergens have been produced in recombinant form, which
      implies standardized quality and unlimited quantity of the respective proteins.
      Hence, such molecules might be used to solve problems of clinical and molecular
      allergology in diagnosis, research, and therapy of class II food allergies. First
      experiments with recombinant food allergens in this respect appear very
      promising.

PMID- 14962765
TI  - Transition of recombinant allergens from bench to clinical application.
AB  - The cloning and production of an increasing number of allergens through the use
      of DNA technology has provided the opportunity to use these proteins instead of
      natural allergen extracts for the diagnosis and therapy of IgE-mediated allergic
      disease. For diagnostic purposes, it is essential that the molecules exhibit IgE
      reactivity comparable with that of the natural wild-type molecules, whereas T
      cell reactivity and immunogenic activity may be more important for allergen
      specific immunotherapy. In relation to the latter, the development of
      hypoallergenic recombinant allergen variants is an approach which shows great
      promise. Clinical application of the proteins requires that they must be produced
      under conditions of Good Manufacturing Practice and meet the specifications set
      down in the appropriate Regulatory Guidelines, principally the ICH-Guidelines.
      Special consideration has to be given to the choice of expression system, the
      design of the expression vectors, and the purification strategy to obtain a pure
      product free from toxins and contamination. The availability of the pure
      recombinant molecules provides the opportunity to formulate preparations that are
      free from the non-allergenic ballast proteins present in natural allergen
      extracts and which contain relative concentrations of the allergens in clinically
      appropriate proportions.

PMID- 14962766
TI  - Strategies for converting allergens into hypoallergenic vaccine candidates.
AB  - Specific immunotherapy is based on the administration of increasing doses of
      allergens to allergic patients with the aim of inducing a state of antigen
      specific unresponsiveness. Specific immunotherapy is one of the few causative
      treatment approaches for Type I allergy but may cause numerous side effects,
      including local inflammatory reactions, systemic manifestations (e.g., asthma
      attacks) and in the worst case, anaphylactic shock which may lead to death.
      Several attempts have been made in the past to reduce the rate of side effects.
      They included the chemical modification of allergen extracts to reduce their
      allergenic activity and the adsorption of allergen extracts to adjuvants to
      prevent the systemic release of allergens after administration. During the last
      decade, cDNAs coding for the most relevant allergens have been isolated and the
      corresponding allergens have been produced as recombinant molecules. Using
      allergen-encoding cDNAs, the amino acid sequence of allergens or purified
      recombinant allergens several strategies can now be applied to produce allergen
      derivatives with reduced allergenic activity for allergy vaccination in a
      controlled and reproducible manner. Currently, allergen-encoding cDNAs are used
      to engineer recombinant hypoallergenic allergen derivatives. According to the
      amino acid sequences and experimental epitope mapping data, synthetic peptides
      representing T- or B-cell epitopes are produced and purified recombinant
      allergens are coupled to novel adjuvants for vaccine formulation. In this
      article, strategies for the production and evaluation of allergen derivatives
      with reduced allergenic activity for allergy vaccination are described. These new
      vaccines hold great promise to improve the current practice of allergen-specific
      immunotherapy and maybe also used for prophylactic vaccination in the future.

PMID- 14962767
TI  - Allergen mimotopes.
AB  - The causative treatment of type I allergies is a long pursued goal in immunology.
      To design safe and efficient vaccine preparations, the interaction of the
      allergen and the symptom-inducing IgE antibodies still needs to be better
      understood. In this article, we describe the use of the phage display technique
      in allergy. It yields epitope mimics, so-called mimotopes, which can be employed
      for both, investigation of allergen-IgE interactions and definition of safe novel
      vaccines.

PMID- 14962768
TI  - DNA vaccines for allergy treatment.
AB  - In the past 10 years, a great number of studies have demonstrated that injection
      of plasmid DNA coding for certain genes results in the induction of humoral and
      cellular immune responses against the respective gene product. This vaccination
      approach covers a broad range of possible applications, including the induction
      of protective immunity against viral, bacterial, and parasitic infections, and it
      opens new perspectives for treatment of cancer. Surprisingly, DNA immunization
      also turned out as a promising novel type of immunotherapy against allergy. In
      this paper, we describe the construction of DNA vaccines for application in
      allergy models. Beyond, we offer a palette of recently developed modulations to
      optimize DNA vaccines for allergy treatment by increasing their immunogenicity
      and minimizing their anaphylactic potential.

PMID- 14962769
TI  - Knocking out expression of plant allergen genes.
AB  - Pollen of many grasses, trees, and weeds are the source of inhalant allergic
      proteins while various other plant products are allergenic only upon their
      ingestion as a food source. Allergenic proteins of pollen are exposed to human
      immune system after their rapid release from pollen upon coming in contact with
      moist surface of nasal mucosa. The advent of molecular cloning and ability to
      genetically transform plants now offer unprecedented opportunities to produce
      hypoallergenic plants by targeted switching off allergen production. Gene
      silencing strategies that operate at post-transcriptional level are highly
      suitable for blocking allergen production. We have demonstrated the concept of
      allergen gene silencing through antisense approach by producing ryegrass plants
      that do not produce major allergen in its pollen. Our results show the potential
      of antisense approach in reducing the allergenic potential of plants. Such a
      strategy can have a general applicability for production of transgenic plants
      depleted of both inhaled and ingested allergens. In addition, such an approach
      could also help in elucidating the in vivo function of allergen(s) in plants and
      contribution of an allergen to overall allergenic potential of an allergen
      source.

PMID- 14962770
TI  - Increased diaphragmatic strength and tolerance to fatigue after bilateral lung
      transplantation: an electromyographic study.
AB  - We evaluated the diaphragmatic function of seven patients with severe chronic
      respiratory failure before and after a bilateral lung transplantation (BLT), with
      follow-up at one year of pulmonary function tests, maximal inspiratory mouth
      pressure (MIP) and surface diaphragmatic electromyogram (Edi). The patients were
      asked to sustain target inspiratory pressures at -15, -30, and -50 cmH(2)O. We
      measured the endurance time (Tlim) to sustain inspiratory efforts and the power
      spectrum density function of Edi at each inspiratory maneuver. The Edi power
      spectra was analysed in terms of median frequency (MF), total power (TP) and
      energies in high-and low-frequency bands (EL and EH). Before BLT, a defect of the
      diaphragmatic function was evident: MIP was 62+/-7% of the predicted value and
      the Tlim measured at each inspiratory effort was very short ( 13+/-1 s, 10+/-1 s
      and 8+/-1 s at pressures of -15, -30, and -50 cmH(2)O, respectively). One month
      after BLT, the Tlim began to increase at all target inspiratory pressures and at
      6 months MIP recovered to normal values. One month after BLT, there was a
      significant decrease in TP measured at the beginning of each inspiratory efforts
      and also an increase in the concomitant MF value. BLT markedly accentuated the
      maximal variations of TP, MF and low-frequency Edi energy. Some hypotheses are
      raised to explain this dramatic improvement in diaphragmatic function after BLT.

PMID- 14962771
TI  - EMG versus oxygen uptake during cycling exercise in trained and untrained
      subjects.
AB  - The aim of this study was to test the hypothesis that bicycle training may
      improve the relationship between the global SEMG energy and VO2. We already
      showed close adjustment of the root mean square (RMS) of the surface
      electromyogram (SEMG) to the oxygen uptake (VO2) during cycling exercise in
      untrained subjects. Because in these circumstances an altered neuromuscular
      transmission which could affect SEMG measurement occurred in untrained
      individuals only, we searched for differences in the SEMG vs. VO2 relationship
      between untrained subjects and well-trained cyclists. Each subject first
      performed an incremental exercise to determine VO2max and the ventilatory
      threshold, and second a constant-load threshold cycling exercise, continued until
      exhaustion. SEMG from both vastus lateralis muscles was continuously recorded.
      RMS was computed. M-Wave was periodically recorded. During incremental exercise:
      (1) a significant non-linear positive correlation was found between RMS increase
      and VO2 increase in untrained subjects, whereas the relationship was best fitted
      by a straight line in trained cyclists; (2) the RMS/VO2 ratio decreased
      progressively throughout the incremental exercise, its decline being
      significantly and markedly accentuated in trained cyclists; (3) in untrained
      subjects, significant M-wave alterations occurred at the end of the trial. These
      M-wave alterations could explain the non-linear RMS increase in these
      individuals. During constant-load exercise: (1) after an initial increase, the
      VO2 ratio decreased progressively to reach a plateau after 2 min of exercise, but
      no significant inter-group differences were noted; (2) no M-wave changes were
      measured in the two groups. We concluded that the global SEMG energy recorded
      from the vastus lateralis muscle is a good estimate of metabolic energy
      expenditure during incremental cycling exercise only in well-trained cyclists.

PMID- 14962772
TI  - Effects of the length ratio between the contractile element and the series
      elastic element on an explosive muscular performance.
AB  - Effects of the length ratio between the contractile element (CE) and the series
      elastic element (SEE) on the behavior of the muscle tendon complex were
      investigated during stretch-shortening cycles. A computer simulation model of the
      Hill-type muscle tendon complex was constructed. The proximal end of the CE was
      affixed to a point in the gravitational field, and a massless supporting object
      was affixed to the distal end of the SEE. A mass was held on the supporting
      object. Initially, the muscle tendon complex was fixed at a certain length, and
      the CE was activated at 100%. Through this process, the CE contracted as much as
      the SEE was stretched. Thereafter, the supporting object was released, which
      caused the muscle tendon complex to propel the mass upward, simulating a stretch
      shortening cycle. The length ratio between the CE and the SEE, the size of the
      mass and the initial length of the CE were sequentially changed. As a result, it
      was found that a higher performance is obtained with a longer SEE when the mass
      is small, while with a shorter SEE when the mass is large.

PMID- 14962773
TI  - Validation of the wavelet spectral estimation technique in biceps brachii and
      brachioradialis fatigue assessment during prolonged low-level static and dynamic
      contractions.
AB  - An experiment was carried out to investigate the myoelectrical manifestations of
      fatigue of the Biceps Brachii and Brachioradialis muscles in low-level (15% MVC)
      prolonged isometric and dynamic contractions. The range of the joint angle was 70
      110 degrees and the mean speed of flexion and extension was about 33.33 degrees
      /s (1.2 s for 40 degrees ). The use of Wavelet transform (IMNF) in weakly
      stationary dynamic SEMG signals was validated in comparison with the Fourier
      transform (MPF). The development of fatigue and its myoelectrical manifestations
      (increase in RMS and decrease in mean frequency) in dynamic contractions show no
      deviations from what is found in literature for both spectral estimation
      techniques. The benefit of Wavelets is its future use in non-stationary
      conditions. Lower IMNF slopes in dynamic compared to isometric contractions for
      Biceps Brachii might be an indication that wavelets reflect more the changes in
      muscle fiber propagation velocity. The results of the use of Wavelet transform in
      detecting frequency modulations in different movement phases of the dynamic tests
      show that in the eccentric phase a systematic shift towards lower frequencies
      occurs. It also reveals the great possibilities of phase separation using
      Wavelets with high resolution and low interaction.

PMID- 14962774
TI  - The effect of skinfold on frequency of human muscle mechanomyogram.
AB  - The aim of the study was to assess the effect of skinfold thickness on median and
      peak frequency of mechanomyographic (MMG) signal in relation to subject's age,
      gender and force during voluntary contraction of elbow flexor and extensor
      muscles. Seventy-nine healthy subjects participated in the study: 22 young
      females (age 20.1+/-1.1 years), 22 young males (age 23.4+/-1.1 years), 17 elderly
      females (age 64.9+/-5.1 years), and 18 elderly males (age 67.4+/-6.2 years).
      Three identical MMG probes were used to record MMG signals from above the triceps
      brachii (TB), biceps brachii (BB), and brachioradialis (BR) muscles
      simultaneously with the force signal. The results showed that the tissue between
      the muscle and the skin surface has a major contribution to the median and a
      minor contribution to the peak MMG frequencies independent of subjects' age (with
      force having more than 2 folds a smaller effect). During antagonistic function of
      the main elbow flexors and extensors, there is a decreasing effect of skinfold
      thickness and an increasing effect of force on the MMG frequency, and the
      relative contribution of both factors to the MMG signal is age related,
      especially in the TB and BR muscles. The BR muscle differs from the TB and BB
      muscles in regard to the effects of skinfold thickness and force on the MMG
      frequency, as well as in the effect of age on the relationship between the MMG
      frequency and skinfold thickness and force. The effect of age on the relative
      contribution of skinfolds and force to MMG frequency is specific for muscle and
      its function. It was concluded that studies that report MMG frequency with
      different values of skinfold thickness cannot be easily compared, especially when
      maximally activated prime movers are tested. A use of force and skinfold
      thickness as covariates is recommended when an MMG frequency is analyzed in
      subjects differing in the skinfold thickness.

PMID- 14962775
TI  - Simulation of the motor units control during a fast elbow flexion in the sagittal
      plane.
AB  - The fact that muscles are composed of different Motor Units (MUs) is often
      neglected when investigating motor control by macro models of human musculo
      skeletal-joint systems. Each muscle is associated with one control signal. This
      simplification leads to difficulties when mechanical and electrical
      manifestations of the muscle activity are juxtaposed. That is why a new approach
      for muscle modelling was recently proposed (Journal of Biomechanics 2002;35:1123
      1135). It is based on MUs twitches and a Hierarchical Genetic Algorithm (HGA) is
      implemented for choosing the moments of activation of the individual MUs, thus
      simulating the control of the nervous system. Its basic benefit is obtaining the
      complete information about the mechanical and activation behaviour of all MUs,
      respectively muscles, during the whole motion. Its possibilities are demonstrated
      when simulating fast elbow flexion. Three flexor and two extensor muscles, each
      consisting of approximately real number of different types of MUs, are modelled.
      The task is highly indeterminate and the optimization is performed according to a
      fitness function that is an assessed combination of criteria (minimal deviation
      from the given joint moment, minimal total muscle force and minimal MUs
      activation). The influence of the weight of the first criterion (the one that
      reflects the importance of the movement accuracy on the predicted results), is
      investigated. Two variants concerning the muscle MUs structure are also compared:
      each muscle is composed of four distinct types MUs and the MUs twitch parameters
      are uniformly distributed.

PMID- 14962776
TI  - Analyses of dynamic co-contraction level in individuals with anterior cruciate
      ligament injury.
AB  - BACKGROUND: A complete understanding of neural mechanisms by which ligament
      receptors may contribute to joint stability is not well established. It has been
      suggested that these receptors may be involved in a neuromuscular process related
      to the modulation of dynamic co-contraction, as a means of guaranteeing
      functional joint stability. HYPOTHESIS: Individuals with ACL injury have
      diminished dynamic co-contraction. STUDY DESIGN: Exploratory, cross-sectional
      design. METHODS: Ten subjects with unilateral ACL injury treated conservatively,
      and ten subjects without history of injury participated in the study. The co
      contraction level was assessed through EMG recordings of the vastus lateralis and
      biceps femoris before and after a perturbation imposed on the subjects during a
      walking task. RESULTS: Subjects with ACL injury presented significantly lower co
      contraction level pre-perturbation (p = 0.045) and post-perturbation (p = 0.046)
      than those in the control group. CONCLUSIONS: The bilateral decrease in muscular
      co-contraction presented by individuals with ACL injury suggests that ligament
      and joint receptors may be responsible for a bilateral dynamic increase in muscle
      and joint stiffness that could result in a greater joint stability. CLINICAL
      RELEVANCE: This study analyzed a neuromuscular mechanism that might contribute to
      the functional stability of the knee joint.

PMID- 14962777
TI  - Can needle-EMG correctly diagnose combinations of two damaged nerves?
AB  - It is accepted that when there is severe, focal nerve damage and an appropriate
      needle-EMG (nEMG) study is carried out, the electromyographer can infer the
      correct diagnosis. But is it a fact? This study will check the inference. In this
      theoretical study, all the possible combinations of two damaged nerve-segments
      were computed and converted into the expected nEMG findings. These nEMG findings
      were interpreted and the results compared with the known nerve damage. To
      facilitate the study, as multiple nEMG findings were analyzed, an automated
      diagnostic program was used. It was found that in the best of cases, only 64% of
      concurrent two-nerve damage could be correctly diagnosed by nEMG as one single
      diagnosis. The rest 36% manifest three types of possible errors: the diagnosis of
      only one of the two damaged nerve-segments; the diagnosis of a wrong nerve
      segment and the diagnosis of one set of damaged nerve-segments, at times the
      wrong one, when multiple possibilities exist. Utilizing diagnostic programs or
      tables as ancillary support in the interpretation of nEMG data may function as a
      second opinion and help electromyographers in ascertaining their own impression.

PMID- 14962778
TI  - Femoral anteversion influences vastus medialis and gluteus medius EMG amplitude:
      composite hip abductor EMG amplitude ratios during isometric combined hip
      abduction-external rotation.
AB  - This prospective study evaluated differences in vastus medialis (VM) and gluteus
      medius (GM) EMG amplitude:composite hip abductor (gluteus maximus, gluteus
      medius, tensor fascia lata) EMG amplitude ratios among subjects with low or high
      relative femoral anteversion. Data were collected during the performance of a non
      weight bearing, non-sagittal plane maximal volitional effort isometric combined
      hip abduction-external rotation maneuver. Eighteen nonimpaired athletically
      active females participated in this surface EMG study. Medial hip rotation
      (relative femoral anteversion estimate) was measured with a handheld goniometer.
      Subjects were grouped by medial hip rotation displacement (group 1 < or = 42
      degrees =36.1+/-7 degrees and group 2 > 42 degrees =52.7+/-7 degrees ) for
      statistical analysis (Mann Whitney U-tests, p < 0.05). Group 2 had decreased VM
      (42+/-23% vs. 69+/-30%, U=19, p=0.034) and GM (62+/-25% vs. 96+/-39%, U=19,
      p=0.034) normalized mean peak EMG amplitude:composite mean peak hip abductor EMG
      amplitude ratios compared to group 1. Decreased normalized VM (-27%) and GM (
      34%) EMG amplitudes among subjects with increased relative femoral anteversion
      suggest reduced dynamic frontal and transverse plane femoral control from these
      muscles, possibly contributing to the increased incidence of non-contact knee
      injury observed among athletic females.

PMID- 14962779
TI  - Relationship between muscle length and moment arm on EMG activity of human
      triceps surae muscle.
AB  - PURPOSE: The purpose of this experiment was to evaluate the effects of both
      muscle length and moment arm (MA) on the electromyographic (EMG) and force output
      of the triceps surae (TS) muscle. RELEVANCE: It is well recognized that changes
      in muscle length affect both the muscle's force generating capacity as well as
      its twitch speed. This relationship is well established in animal preparations.
      Contrary to animal experiments where length can be directly manipulated in
      isolated muscles, human experiments require that all muscle length changes be
      secondary to changes in a joint angle. Such experimental manipulations therefore
      produce changes in not only muscle length, but also in the muscle's MA. The
      relative effect of muscle length and MA changes on muscle EMG has not been
      determined in previous experiments. METHODS: This study was executed in two
      phases. First, using fresh human cadaver lower limbs, data were gathered
      describing the relationship between knee and ankle angle changes for maintenance
      of a constant TS muscle length, while its MA at the ankle joint has been changed.
      In the second phase of the study, results obtained from phase one were applied to
      10 healthy adult human subjects to measure the EMG (surface and fine wire)
      activity of TS at three different conditions: when both length and MA were
      shortened, when muscle length was decreased given a constant MA and when MA was
      shortened given a constant muscle length. RESULTS: A significant increase in
      muscle activity was found as both the length and MA of TS muscle were shortened.
      A similar pattern of increased muscle activity was observed when the MA was
      shortened given a constant muscle length. No significant change in TS activity
      was found when muscle length was shortened, given a constant MA at the ankle
      joint. CONCLUSIONS: The findings of this study indicate that changes in the
      Achilles tendon MA predominate over the muscle length variations in determining
      the level of TS activity when generating plantar flexion torque.

PMID- 14962780
TI  - Footprint analysis of gait using a pressure sensor system.
AB  - The purpose of this study was to investigate if the detailed pressure data of the
      footprints of normal gait add essential information to the spatio-temporal
      variables of gait. The gait of 62 healthy adult subjects was investigated using
      GAITRite pressure sensor system. Each footprint was divided into 12 equal
      trapezoids and after that the hindfoot, midfoot and forefoot analysis was
      developed. A typical activation pattern of the sensors with two peaks of active
      area and peak pressure distribution during normal walking was obtained. The first
      peak reflected the heel strike, and the second peak reflected push-off at the end
      of the stance phase. The lowest pressure values were in the midfoot, where the
      lateral part of the foot activated sensors more than the medial part. The
      footprint patterns of right and left legs were symmetrical and corresponded with
      the symmetry found in the spatio-temporal variables of gait. The variability for
      the active area and the peak pressure were more pronounced for the lateral part
      of the midfoot and a smaller variation was seen in areas with concentrated
      observations (e.g. 1st, 2nd and 5th lateral trapezoids). Increasing active area
      in the forefoot was associated with decreasing pressure sensor activity in the
      midfoot. The footprint patterns identified the symmetry between the legs and at
      the same time revealed the velocity performance.

PMID- 14962781
TI  - Effect of needle-EMG on blood-pressure and heart-rate.
AB  - Though immediate pain is reported by nearly all patients undergoing needle-EMG,
      little is known about its cardiovascular risk from changes in blood-pressure or
      heart-rate. This study was thus conducted to investigate if, and to which degree,
      blood-pressure and heart-rate are influenced by needle-EMG. In 50 patients, 24
      women, 26 men, aged 26-78 years, conventional needle-EMGs from 54 muscles were
      recorded. Pain was assessed on a verbal analogue pain-scale (1-10) and blood
      pressure and heart-rate were measured before, during and after EMG. Mean pain
      ratings before, during and after EMG were 0.8, 4.1 and 1.0, respectively. Mean
      systolic/diastolic blood-pressure was 144/87 mmHg before, 145/86 mmHg during and
      144/87 mmHg after EMG. Mean heart-rate before, during and after EMG was 77, 77
      and 78 beats/min, respectively. Systolic/diastolic blood-pressure increased above
      145/85 mmHg in only 2/6 patients during EMG. The weak affection of blood-pressure
      and heart-rate by pain from needle-EMG was found in patients with and without
      hypertension. Mean blood-pressure, heart-rate and pain-ratings before, during and
      after EMG were independent of age, sex and muscle. The correlation between pain
      ratings and blood-pressure and heart-rate was not significant. This study shows
      that needle-EMG moderately hurts but does not increase blood-pressure or heart
      rate, irrespective of known arterial hypertension. Based upon these findings, the
      cardiovascular risk of needle-EMG from changes in blood-pressure or heart-rate is
      regarded negligibly low.

PMID- 14962783
TI  - Drug resistance in non-subtype B HIV-1.
AB  - Treatment of HIV-1 with antiretroviral therapy may select mutations in the pol
      gene associated with resistance to reverse transcriptase inhibitors and protease
      inhibitors. To provide durable clinical benefit, emergence of drug resistance is
      countered by prescription of alternative drug regimens. Data on sequential
      treatments that are effective after virologic failure and the selection of drug
      resistance is largely confined to HIV-1 subtype B, the clade that has circulated
      in North America and Europe. However, HIV-1 subtype B currently accounts for only
      12% of the estimated 40 million HIV infected individuals worldwide. The global
      HIV-1 epidemic includes infection with nine identified HIV-1 group M subtypes (A
      K), as well as distinct sub-subtypes and numerous chimerical or recombinant
      forms. Increasing access to treatment of HIV-1 in the developing world and
      increasing non-subtype B infection through travel and migration pose new
      questions about the susceptibility and response of these diverse HIV-1 viruses to
      antiretroviral drugs. Here we review HIV diversity and the published literature
      on drug resistance, comparing the known resistance mutations in individuals
      infected with subtype B to the growing experience in the treatment of non-subtype
      B HIV-1 worldwide.

PMID- 14962785
TI  - Laboratory-acquired vaccinia infection.
AB  - BACKGROUND: Complications following vaccination with vaccinia virus have been
      well described but are not commonly observed. The use of vaccinia as a tool in
      molecular biology, in the development of therapeutics, and the anticipated
      increase of vaccinations in the general population due to the threat of
      bioterrorism have created a renewed awareness of the post-vaccination
      complications and the consequent need for clinical and laboratory diagnosis.
      OBJECTIVES: To report the clinical presentation and subsequent diagnosis of
      generalized vaccinia that resulted from a laboratory accident in an unvaccinated
      subject. STUDY DESIGN: The patient was seen by a local infectious disease's
      specialist and evaluated clinically and with laboratory support relative to a
      differential diagnosis. RESULTS: Careful assessment of the patient's history, an
      evaluation of the workplace, and the elimination of likely microbial etiologies
      led to the diagnosis of generalized vaccinia. Laboratory confirmation was
      obtained by use of electron microscopy (EM) to observe poxvirus particles in
      infected cell cultures. CONCLUSIONS: Exposure to vaccinia virus should raise the
      index of suspicion for patients with skin lesions. Rapid diagnosis may be
      accomplished by direct examination of lesion material by EM. The virus also
      readily replicates in commonly available cell cultures and in the absence of
      immune reagents, typical poxvirus particles may be observed in the infected cells
      by EM.

PMID- 14962784
TI  - Occult hepatitis B virus infection does not affect liver histology or response to
      therapy with interferon alpha and ribavirin in intravenous drug users with
      chronic hepatitis C.
AB  - BACKGROUND: the frequency and the impact of occult HBV infection in patients with
      chronic hepatitis C infection is still a matter of some controversy. OBJECTIVES:
      our aim was to evaluate the prevalence of occult HBV infection and assess its
      impact on liver biochemistry, HCV viral titre, liver histology and on outcome of
      therapy in patients with chronic hepatitis C. STUDY DESIGN: paired liver biopsies
      and serum samples were collected from 51 patients (84% IVDUS) with HBsAg negative
      chronic hepatitis C, and tested for HBV-DNA with nested PCR. Liver biopsies were
      further studied histologically, with morphometric analyses and immunostaining
      techniques. Twenty-five were treated with alpha Interferon and ribavirin and
      followed for at least 18 months. RESULTS: HBV DNA was detected in 29.4% of liver
      tissue specimens and in only one (1.9%) serum sample. Three liver specimens were
      positive for surface gene, nine for core gene, three for both and none for the X
      gene. No significant difference in mean transaminase values, HCV viral titre, HCV
      genotype, or grading and staging and morphometric analysis was observed in
      patients with or without HBV DNA. Moreover, all 51 liver specimens were negative
      for both HBsAg and HBcAg. Sustained response to combination therapy was achieved
      in 40% of patients with and in 53% of patients without HBV DNA in the liver
      specimens (P=NS). CONCLUSIONS: HBV DNA is frequently found in the liver of
      patients with chronic hepatitis C. However, the lack of any significant impact on
      HCV viral titre, liver enzymes, histological parameters and response to therapy,
      suggests that in most cases HBV DNA detected in the liver by PCR may be either an
      integrated or low level replicative form.

PMID- 14962786
TI  - Automated detection of five human herpes virus DNAs by a set of LightCycler PCRs
      complemented with a single multiple internal control.
AB  - BACKGROUND: Herpes viruses represent important causes of morbidity and mortality
      especially in immuno-compromised patients. To assist in rapid diagnosis real-time
      PCR assays have been developed for the detection of herpes virus DNA in patient
      specimens. A recently described set of real-time PCR assays using LightCycler
      technology enabled parallel detection of DNA from cytomegalovirus (CMV), Epstein
      Barr virus (EBV), herpes simplex virus type 1 and 2 (HSV-1/-2), and varicella
      zoster virus (VZV) by using a single LightCycler program [J. Clin. Virol. 26
      (2003) 85]. The set of assays lacked automation of DNA purification and of PCR
      mixture preparation, and was not furnished with measures to monitor for sample
      adequacy. OBJECTIVES: Development of a set of automated LightCycler-PCR assays
      for the detection CMV-, EBV-, HSV-1/-2- and VZV-DNA in plasma samples and
      complementation of the assays with internal amplification controls (ICs). STUDY
      DESIGN: The MagNA Pure LC instrument was used for automated DNA purification and
      automated preparation of PCR mixtures. A single multiple IC-DNA specific for all
      four herpes virus type-specific PCRs was generated and used in all four
      LightCycler assays. Detection limits were determined and clinical samples were
      evaluated. RESULTS: With quantified herpes virus type-specific reference DNA
      spiked into EDTA plasma, the detection limits were found at 250 copies/ml of CMV
      , EBV-, HSV-1/-2-DNA and at 500 copies/ml of VZV-DNA. The novel set of assays was
      evaluated by testing 112 EDTA plasma samples. The use of the IC led to the
      detection of PCR-inhibited samples. CONCLUSION: The set of automated LightCycler
      assays was found rapid, markedly labour saving and suitable for the routine
      diagnostic laboratory. The use of the one internal control molecule simplified
      the assay protocol and allowed monitoring for sample adequacy.

PMID- 14962787
TI  - Design and performance testing of quantitative real time PCR assays for influenza
      A and B viral load measurement.
AB  - BACKGROUND: The antiviral effect of anti-influenza drugs such as zanamivir may be
      demonstrated in patients as an increased rate of decline in viral load over a
      time course of treatment as compared with placebo. Historically this was measured
      using plaque assays, or Culture Enhanced Enzyme Linked Immunosorbent Assay (CE
      ELISA). OBJECTIVES: to develop and characterise real time quantitative PCR (qPCR)
      assays to measure influenza A and B viral load in clinical samples, that offer
      improvements over existing methods, in particular virus infectivity assays. STUDY
      DESIGN: The dynamic range and robustness were established for the real time qPCR
      assays along with stability of the assay components. Cross validation of the real
      time PCR assays with CE-ELISA was performed by parallel testing of both serial
      dilutions of three different subtypes of cultured virus and a panel of influenza
      positive throat swab specimens. RESULTS: the assays were specific for influenza A
      and B and the dynamic ranges were at least seven logs. The assay variability was
      within acceptable limits but increased towards the lower limit of quantification,
      which was 3.33 log(10) viral cDNA copies/ml of virus transport medium (ten viral
      RNA copies/PCR). The components of the assay were robust enough to withstand
      extended storage and several freeze-thaw cycles. For the real time PCR assays the
      limit of quantification was equivalent to the virus infectivity cut off, which
      equates to a 93-fold increase in sensitivity. CONCLUSION: Well characterised real
      time PCR assays offer significant improvements over the existing methods for
      measuring the viral load of strains of influenza A and B in clinical specimens.

PMID- 14962788
TI  - Role of rotaviruses in children with acute diarrhea in Tehran, Iran.
AB  - BACKGROUND: Rotavirus illness is associated with significant cause of morbidity
      and is a common cause of hospitalization worldwide. OBJECTIVE: This study was
      performed to assess the role of rotaviruses in children presenting with acute
      diarrhea in two main Children's Medical Centers and one general hospital in
      Tehran. STUDY DESIGN: Stool specimens from 704 children less than 5 years of age
      suffering from diarrhea were tested for the presence of rotaviruses by a
      monoclonal antibody-based enzyme immunoassay. A total of 176 fecal specimens
      collected from healthy children in similar age group were studied as controls.
      RESULTS: Rotavirus antigen was detected in 15.3% of patients. Infants between 6
      and 12 months of age were most frequently affected. Rotavirus infection was
      significantly less frequent in breast-fed than among bottle-fed babies. Watery
      diarrhea was present in 68.5% of children. Detection rate was highest in the
      spring and lowest in summer. Rotavirus can be regarded as a major etiologic agent
      of acute diarrhea in infants and children up to 5-years-old in Iran, immunization
      at birth may protect the children before their first symptomatic infection.

PMID- 14962789
TI  - Quantitative analysis of HCMV DNA load in whole blood of renal transplant
      patients using real-time PCR assay.
AB  - BACKGROUND: Preemptive antiviral treatment of Human Cytomegalovirus (HCMV)
      disease is a major goal in the management of organ transplant patients. It
      requires sensitive diagnostic methods. Automated real-time PCR systems have been
      recently proposed to monitor HCMV infection in such patients. OBJECTIVE:
      Objectives of this study was to compare a real-time quantitative PCR on whole
      blood with the HCMV pp65 antigenemia assay in renal transplant recipients, and
      also to evaluate two different DNA extraction methods. STUDY DESIGN: A total of
      248 specimens from 21 patients were tested by quantitative pp65 antigenemia and
      quantitative real-time PCR. DNA was extracted from whole blood samples using two
      different methods: a conventional column manual assay and an automated system.
      RESULTS: Quantification of HCMV DNA using the two extraction methods showed
      highly similar results (Spearman rank test, r=0.863). We found a significant
      correlation between DNA quantification by real-time PCR in whole blood and pp65
      antigenemia test (Spearman rank test, r=0.767). This correlation was not modified
      when the HCMV DNA results were normalized by quantification of the albumin
      cellular gene. In eight patients, HCMV infection was detected earlier with
      quantitative PCR than with the antigenemia test (mean delay of 11.25 days). HCMV
      DNA load equivalent of 50 pp65 positive cells/200,000 polymorphonuclear
      leukocytes (PMNLs) is log4.095 copies per ml of blood. CONCLUSIONS: Real-time PCR
      in whole blood is a sensitive method for estimating the HCMV genome load in renal
      transplant patients, and is more rapid and practicable than using PMNLs for pp65
      antigenemia tests.

PMID- 14962790
TI  - High prevalence of human papillomavirus type 58 in Mexican colposcopy patients.
AB  - BACKGROUND: Cervical cancer is the second most common cancer of the women
      worldwide. Infection with some genotypes of human papillomavirus is the most
      important risk factor associated to cervical cancer. OBJECTIVE: To determine the
      prevalence and genotypes of papillomavirus in biopsies of women with squamous
      intraepithelial lesion and cervical cancer. STUDY DESIGN: Two hundred sequential
      patients of colposcopy clinic were studied. HPV diagnosis was done by polymerase
      chain reaction using MY09/MY11 primers, for genotyping line blot hybridization
      was used. RESULTS: A total of 186 women were beta globin positive; 104 (55.9%)
      had histology diagnosis of low-grade squamous intraepitelial lesions (LSIL), 67
      (36.0%) high-grade squamous intraepitelial lesions (HSIL) and 15 (8.1%) invasive
      cervical cancer (IC). The prevalence of HPV was 56.4% (104/185); HPV 58 was
      founded in 28.5% of all positive women, HPV 16 in 25.7%, HPV 18 in 13.3%, HPV 33
      in 11.4% and 31 in 8.5%. In all grades of the lesions HPV 58 was the most
      frequently. CONCLUSIONS: The high prevalence of HPV 58 among Mexican women with
      HSIL and IC, has important implications in prophylaxis.

PMID- 14962792
TI  - Inhaled dexamethasone differentially attenuates disease relapse and established
      allergic asthma in mice.
AB  - Inhaled glucocorticoids are effective in patients with chronic allergic asthma.
      We examined the effects of inhaled glucocorticoids on relapse (allergen challenge
      after disease remission) and established/overt allergic asthma (repeated allergen
      challenge in weekly intervals) in mice to establish a reference standard for
      novel treatments. BALB/c mice were treated before relapse or during overt disease
      with 1 h of nebulized PBS or 10 mg% dexamethasone twice daily for 5 days.
      Dexamethasone eliminated airway hyperresponsiveness before relapse and during
      overt disease. They more efficiently reduced airway inflammation, mucus
      production, and OVA-specific IgG1 and IgE during relapse compared to overt
      disease. However, during overt disease, parenchymal inflammatory infiltrates were
      more effectively eliminated compared to relapse, suggesting that activated
      infiltrating leukocytes have increased sensitivity to steroids. These data
      demonstrate that inhaled corticosteroids attenuate relapse and overt disease
      differentially and suggest that both airway and parenchymal inflammation need to
      be evaluated for treatment efficacy.

PMID- 14962793
TI  - Clinical, immunologic and genetic analysis of 29 patients with autosomal
      recessive hyper-IgM syndrome due to Activation-Induced Cytidine Deaminase
      deficiency.
AB  - Mutations of the Activation-Induced Cytidine Deaminase (AID) gene have been found
      in patients with autosomal recessive hyper-IgM (HIGM) syndrome type 2. We
      retrospectively analyzed clinical, immunologic and genetic characteristics of 29
      patients from 22 families with AID deficiency. Patients' median age at diagnosis
      and at last evaluation was 4.9 years (range: 0 to 53) and 14.2 years (range: 2.7
      to 63), respectively. Most patients had suffered from recurrent and severe
      infections, however, intravenous immunoglobulin (IVIG) replacement therapy
      resulted in a dramatic decrease in the number of infections. Lymphoid hyperplasia
      developed in 22 patients and persisted in 7 at last follow-up. It is striking to
      note that six patients developed autoimmune or inflammatory disorders including
      diabetes mellitus, polyarthritis, autoimmune hepatitis, hemolytic anemia, immune
      thrombocytopenia, Crohn's disease and chronic uveitis. Fifteen distinct AID
      mutations were found but there was no significant genotype-phenotype correlation.
      In conclusion, AID-deficient patients are prone to infections and lymphoid
      hyperplasia, which may be prevented by early-onset IVIG replacement, but also to
      autoimmune and inflammatory disorders.

PMID- 14962794
TI  - Autoantibodies to protein transport and messenger RNA processing pathways:
      endosomes, lysosomes, Golgi complex, proteasomes, assemblyosomes, exosomes, and
      GW bodies.
AB  - Over 50 years ago the lupus erythematosus (LE) cell phenomenon was described and
      this was quickly followed by the introduction of the LE cell test and indirect
      immunofluorescence (IIF) to detect antinuclear antibodies (ANA) in clinical
      laboratories. Recently, attention has turned to the identification of the
      autoantigens that bind to cytoplasmic organelles such as the Golgi complex,
      endosomes and other "cytoplasmic somes". Three endosome autoantigens include
      early endosome antigen 1 (EEA1, 160 kDa), cytoplasmic linker protein-170 (CLIP
      170, 170 kDa), and lysobisphosphatidic acid (LBPA). Antibodies to EEA1 were seen
      in a variety of conditions but approximately 40% of the patients had a
      neurological disease. Despite the prominence of lysosomes in cells and tissues,
      reports of autoantibodies are limited to the lysosomal antigen h-LAMP-2 and the
      cytoplasmic antineutrophil antibodies (cANCA). Autoantigens in the Golgi complex
      include giantin/macrogolgin, golgin-245, golgin 160, golgin-97, golgin 95/gm130,
      and golgin-67. More recently, there has been an interest in autoantibodies that
      bind components of the "SMN complex" or the "assemblyosome". Arginine/glycine
      (RG)-rich domains in components of the SMN complex interact with Sm, like-Sm
      (LSm), fibrillarin, RNA helicase A (Gu), and coilin proteins, all of which are
      antigen targets in a variety of diseases. More recently, components of a novel
      cytoplasmic structure named GW bodies (GWBs) have been identified as targets of
      human autoantibodies. Components of GWBs include GW182, a unique mRNA-binding
      protein, like Sm proteins (LSms), and decapping (hDcp1) and exonuclease (Xrn)
      enzymes. Current evidence suggests that GWBs are involved in the cytoplasmic
      processing of mRNAs. Autoantibodies to the "cytoplasmic somes" are relatively
      uncommon and serological tests to detect most of them are not widely available.

PMID- 14962795
TI  - Anti-fetal immune response mechanisms may be involved in the pathogenesis of
      placental abruption.
AB  - Placental abruption is an unpredictable severe complication in pregnancy. In
      order to investigate the possibility that the activation of the fetal nonadaptive
      immune system may be involved in the pathogenesis of this disease, IL-6 release
      from cord blood monocytes was examined by intracellular cytokine staining and
      flow cytometric analysis. Our results demonstrate that preterm placental
      abruption (n = 15) in contrast to uncontrollable preterm labor (n = 33) is
      associated with significantly (P < 0.001) increased release of IL-6 from the
      fetal monocytes. The same holds true for rhesus disease (n = 9, P < 0.001) that
      is characterized by a maternal production of antibodies against the rhesus-D
      antigen expressed by the fetal erythrocytes. This suggests that during rhesus
      disease, IL-6 release of monocytes is induced by antibody-mediated cross-linking
      of these cells to the erythrocytes in the fetal circulation. Hence, this
      assumption favors the idea that also in case of placental abruption, an increased
      maternal antibody production against paternal antigens leads to an elevated IL-6
      release by the fetal monocytes. To elucidate this potential mechanism, the
      presence of anti-HLA-antibodies was assessed in the maternal circulation of
      patients with placental abruption (n = 17) and patients with uncontrollable
      preterm labor (n = 29). The percentage of women producing anti-paternal HLA
      antibodies was significantly (P < 0.01) increased in the group of women with
      preterm placental abruption (47%) in comparison to women with uncontrollable
      preterm labor (14%). Therefore, our results suggest that an increased humoral
      immune response of the mother against the fetus may be decisively involved in the
      pathogenesis of placental abruption.

PMID- 14962796
TI  - Neutralization of interleukin-17 aggravates dextran sulfate sodium-induced
      colitis in mice.
AB  - We evaluated the effects of rat anti-mouse IL-17 neutralizing monoclonal antibody
      (mAb) on the development of dextran sulfate sodium (DSS)-induced colitis. Tissue
      samples were evaluated by standard immunohistochemical procedure. The mucosal
      mRNA expression of cytokines was analyzed by reverse transcriptase-polymerase
      chain reaction (RT-PCR). In the mice treated with the anti-IL-17 mAb, the body
      weight was significantly lower, and anal prolapse and colon shortening were
      apparent. A histological analysis indicated that the anti-IL-17 mAb markedly
      enhanced the severity of colitis. The mucosal infiltration of CD4-positive helper
      T cells and CD11b-positive granulocytes-monocytes was increased in the anti-IL-17
      mAb-treated mice. Treatment with the anti-IL-17 mAb increased the mucosal
      expression of mRNAs of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma,
      IL-6, RANTES, and IP-10. Blocking of IL-17 activity in vivo using the anti-IL-17
      mAb enhanced the development of DSS-colitis in mice. This suggests an inhibitory
      role for IL-17 in the development of DSS-colitis.

PMID- 14962797
TI  - Abnormal development of thymic dendritic and epithelial cells in human X-linked
      severe combined immunodeficiency.
AB  - The X-linked form of severe combined immunodeficiency (X-SCID) is caused by
      mutations in the common cytokine receptor gamma chain and results in lack of T
      and NK cells and defective B cells. Without immune reconstitution, X-SCID
      patients typically die from infection during infancy. This report describes
      thymic epithelial (TE), lymphocyte, and dendritic cell (DC) differentiation in
      the thymic microenvironment of seven X-SCID patients who died before or after
      treatment for their immunodeficiency. X-SCID thymus consisted predominately of TE
      cells without grossly evident corticomedullary distinction. CD3+ and CD1a+
      developing T cells and CD83+ thymic DC were reduced >50-fold when compared to age
      and gender-matched control thymus (P < 0.001). TE expression of epithelial
      differentiation markers CK14, involucrin, and high molecular weight cytokeratins
      also differed in X-SCID versus normal thymus. These histopathologic findings
      indicate that in addition to T cells, thymic DC development and differentiation
      of TE cells are also abnormal in X-SCID.

PMID- 14962798
TI  - Identification of RANTES as a novel immunomodulator of the maternal allogeneic
      response.
AB  - We investigated the immunomodulatory role of chemokines in the maternal
      allogeneic T-cell response. In comparison with fertile women, we found in
      patients with recurrent spontaneous abortions (RSA), a significant decreased sera
      level of RANTES that increased after immunization with paternal leukocytes. Since
      blocking factors with unknown identity are detected in sera from fertile women,
      we hypothesized that RANTES might function as a novel blocking factor and
      therefore we explored its cell growth inhibitory properties during the allogenic
      T-cell response. We demonstrated that RANTES inhibits the mixed lymphocyte
      reaction (MLR) in a dose-dependent manner. Investigation of the mechanisms
      involved in cell growth inhibition revealed that this beta-chemokine induces T
      cell apoptosis through modulation of Bcl-2 protein levels and by a caspase
      independent mechanism and does not involve modulation of Fas (CD95) antigen
      expression. Our results provides experimental evidence implicating RANTES as a
      suppressor of alloantigen specific T-cell responses and indicates that this beta
      chemokine might function as a novel blocking factor and reliable marker for
      successful allotreatment of RSA patients.

PMID- 14962799
TI  - Human hepatic lymph nodes contain normal numbers of mature myeloid dendritic
      cells but few plasmacytoid dendritic cells.
AB  - We investigated whether the hyporesponsiveness of the adaptive arm of the liver
      immune system is related to the composition of the dendritic cell (DC) population
      in hepatic lymph nodes. Noninflamed human hepatic lymph nodes (LN) were obtained
      from multiorgan donors, inflamed hepatic LN from liver transplant recipients with
      autoimmune cholestatic liver diseases, and inguinal LN from kidney transplant
      recipients. Quantitative immunohistochemistry showed that all three types of LN
      contained comparable numbers of mature and immature myeloid DC, but that
      noninflamed and inflamed hepatic LN contained significantly fewer plasmacytoid DC
      as compared to inguinal LN. Likewise, DC-enriched cell preparations from hepatic
      LN contained relatively few plasmacytoid DC. The difference in numbers of
      plasmacytoid DC was confirmed in comparisons of hepatic LN and ileacal LN from
      the same organ-donors. Myeloid DC from hepatic LN showed similar expressions of
      HLA-DR, CD83, and CD86, and higher expression of CD80 compared to myeloid DC from
      inguinal LN. In conclusion, hepatic LN contain similar numbers of myeloid DC as
      muscle/skin lymph-draining LN, with no signs of immaturity, but relatively few
      plasmacytoid DC.

PMID- 14962800
TI  - Utilizing Fcepsilon-Bak chimeric protein for studying IgE-FcepsilonRI
      interactions.
AB  - We previously constructed a pro-apoptotic Fcepsilon-Bak chimeric protein,
      targeted against cells expressing the IgE high affinity receptor (FcepsilonRI).
      We demonstrated that the chimeric protein is internalized by target mast cells
      and kills them. These results, which constitute a promising basis for applying
      this approach to antiallergic therapy, raise some theoretical questions with
      respect to two major issues: (a) is the monomeric Fcepsilon-Bak-FcepsilonRI
      complex able to undergo endocytosis, and (b) does the receptor binding domain of
      human IgE (Fcepsilon) react with rodent FcepsilonRI? In an attempt to answer
      these questions, we have now thoroughly investigate the interaction of human (h)
      and mouse (m) Fcepsilon-Bak with FcepsilonRI-positive cells. Using established
      cultures of rodent and human origin, as well as a primary mouse mast cell
      culture, we demonstrate that binding of the chimeric protein to the membrane is
      followed by quick endocytosis, leading to the apoptosis of specific cells. We
      also confirm that this interaction depends on FcepsilonRI and not on other IgE
      receptors. We found that the effect of Fcepsilon-Bak on the cells depends on the
      level of surface FcepsilonRI expression, but not on the origin of the target
      cells or of the Fcepsilon moiety. We suggest that endocytosis of the monomeric
      Fcepsilon-Bak-FcepsilonRI complex results from the inability of Fcepsilon-Bak to
      transduce signals, characteristic of the monomeric IgE-FcepsilonRI complex due to
      the absence of the variable portion of the IgE molecule. Our results also
      indicate that at least the Fc fragment of human IgE is able to interact with both
      human and rodent FcRI.

PMID- 14962801
TI  - Effects of green tea polyphenols on murine transplant-reactive T cell immunity.
AB  - Green tea polyphenols (GrTP), the active ingredient of green tea, may have
      immunosuppressive properties, but whether and how GrTP affect transplant-reactive
      T cells is unknown. To address this, we tested the effects of GrTP on in vitro
      and in vivo transplant-reactive T cell immunity. GrTP inhibited IFNgamma
      secretion by cultured monoclonal T cells and by alloreactive T cells in mixed
      lymphocyte reactions. Oral GrTP significantly prolonged minor antigen-disparate
      skin graft survival and decreased the frequency of donor-reactive interferon
      gamma-producing T cells in recipient secondary lymphoid organs compared to
      controls. In contrast to other hypothesized actions, oral GrTP did not alter
      dendritic cell trafficking to lymph nodes or affect metalloproteinase activity in
      the graft. This is the first report of an immunosuppressive effect of GrTP on
      transplant-reactive T cell immunity. The results suggest that oral intake of
      green tea could act as an adjunctive therapy for prevention of transplant
      rejection in humans.

PMID- 14962802
TI  - Mitf-PU.1 interactions with the tartrate-resistant acid phosphatase gene promoter
      during osteoclast differentiation.
AB  - It has been postulated that the transcription factors micropthalmia associated
      factor (Mitf) and PU.1 interact with the tartrate-resistant acid phosphatase
      (TRAP) gene promoter and activate TRAP gene expression in osteoclasts. However,
      studies on the interaction of these factors with the TRAP promoter employing
      nuclear extracts from osteoclasts and osteoclast precursors have not been
      reported. We therefore treated murine mononuclear phagocyte cells with various
      cytokines to generate cultures of osteoclasts and macrophagic cells with high or
      low potential to form osteoclasts. The presence of Mitf and PU.1 in nuclear
      extracts from these cultures and the ability of these factors to bind to the TRAP
      promoter was then assessed. We demonstrate that Mitf and a related factor, TFE3,
      are present in nuclear extracts from all cultures and bind the TRAP promoter.
      While PU.1 is present in nuclear extracts from all cultures, it does not
      significantly interact with a putative binding site in the TRAP promoter. These
      results suggest Mitf and PU.1 interactions with the TRAP promoter are not
      responsible for the specific activation of TRAP gene expression in osteoclasts.

PMID- 14962803
TI  - CMF608-a novel mechanical strain-induced bone-specific protein expressed in early
      osteochondroprogenitor cells.
AB  - Microarray gene expression analysis was utilized to identify genes upregulated in
      primary rat calvaria cultures in response to mechanical force. One of the
      identified genes designated CMF608 appeared to be novel. The corresponding full
      length cDNA was cloned and characterized in more details. It encodes a putative
      2597 amino acid protein containing N-terminal signal peptide, six leucine-rich
      repeats (LRRs), and 12 immunoglobulin-like repeats, 10 of which are clustered
      within the C-terminus. Expression of CMF608 is bone-specific and the main type of
      CMF608-positive cells is mesenchymal osteochondroprogenitors with fibroblast-like
      morphology. These cells reside in the perichondral fibrous ring of La Croix,
      periosteum, endosteum of normal bone as well as in the activated periosteum and
      early fibrous callus generated postfracture. Expression of CMF608 is notably
      absent from the regions of endochondral ossification. Mature bone cell types do
      not produce CMF608 with the exception of chondrocytes of the tangential layer of
      the articular cartilage, which are thought to be under constant mechanical
      loading. Ectopic expression of CMF608 in HEK293T cells shows that the protein is
      subjected to post-translational processing and its N-terminal approximately 90
      kDa polypeptide can be found in the conditioned medium. Ectopic expression of
      either the full-length cDNA of CMF608 or of its N-terminal region in CMF608
      negative ROS17/2.8 rat osteosarcoma cells results in transfected clones
      displaying increased proliferation rate and the characteristics of less
      differentiated osteoblasts compared to the control cells. Our data indicate that
      CMF608 is a unique marker of early osteochondroprogenitor cells. We propose that
      it could be functionally involved in maintenance of the osteochondroprogenitor
      cells pool and its down-regulation precedes terminal differentiation.

PMID- 14962804
TI  - Mechanotransduction in the cortical bone is most efficient at loading frequencies
      of 5-10 Hz.
AB  - A dose-response relationship has been shown between loading frequency and
      cortical bone adaptation for frequencies of up to 10 Hz, and is presumed to
      persist with further increases in frequency. Studies herein aimed to investigate
      cortical bone adaptation to loading frequencies of 1, 5, 10, 20 and 30 Hz. Two
      studies were performed in adult C57BL/6 mice using the ulna axial compression
      loading model. In the first study, the histomorphometric response of the ulna was
      studied when loaded for 120 cycles day(-1) for 3 days at one of the five
      frequencies and one of two load magnitudes (1.5 or 2.0 N). In the second study,
      the changes in ulna geometry and mechanical properties were studied following
      loading for 5 min day(-1), 3 days week(-1) for 4 weeks at one of the five
      frequencies and one of two load magnitudes (1.0 or 1.6 N). Preliminary strain
      gauge measurements showed that frequency had no effect on mechanical strain per
      unit load. In study 1, loading frequency significantly influenced bone adaptation
      when loading at 2.0 N, with loading at 10 Hz resulting in significantly greater
      adaptation than with loading at other frequencies. In study 2, loading frequency
      significantly influenced the change in geometry when loading at 1.6 N, with
      loading at 5, 10 or 30 Hz resulting in significantly greater change than with
      loading at 1 Hz. Loading at 5 Hz also resulted in significantly greater change
      than with loading at 20 Hz. No frequency effect was found on any of the
      mechanical properties at either load. Overall, we found cortical bone adaptation
      to mechanical loading to increase with increasing loading frequency up to 5-10 Hz
      and to plateau with frequencies beyond 10 Hz. The mechanism for this nonlinear
      frequency response is not known; however, based on strain gauge measurements, we
      do not believe it resulted from dampening associated with high frequency loading
      through the flexed carpal joint. The obtained findings may relate to the
      mechanism of mechanotransduction within the bone. This requires further
      investigation.

PMID- 14962805
TI  - Sutural bone deposition rate and strain magnitude during cranial development.
AB  - It is widely believed that rapid growth of the human brain generates tensile
      strain in cranial sutures, and that this strain influences the rate of bone
      deposition at the sutural margins during development. We developed general
      theoretical techniques for estimating sutural bone deposition rate and strain
      magnitude during mammalian cranial development. A geometry-based analysis was
      developed to estimate sutural bone deposition rate. A quasi-static stress
      analysis was developed to estimate sutural strain magnitude. We applied these
      techniques to the special case of normal cranial development in humans. The
      results of the bone deposition rate analysis indicate that average human sutural
      bone deposition rate is on the order of 100 microm/day at 1 month of age and
      decreases in an approximately exponential fashion during the first 4 years of
      life. The results of the strain analysis indicate that sutural strain magnitude
      is highly dependent on the assumed stiffness of the sutures, with estimated
      strain at 1 month of age ranging from approximately 20 to 400 microstrain.
      Regardless of the assumed stiffness of the sutures, the results indicate that
      sutural strain magnitude is small and decreases in an approximately exponential
      fashion during the first 4 years of life. The finding that both sutural bone
      deposition rate and strain magnitude decrease with increasing age is consistent
      with quasi-static tensile strain in sutures influencing sutural osteoblast
      activity in a dose-dependent manner. However, the small magnitude of the
      predicted strains suggests that tissue level strains in sutures may be too small
      to directly influence osteoblast biology. In light of these results, we suggest
      other biomechanical mechanisms, such as a tension-induced angiogenic environment
      in the sutures or mechanotransduction in the underlying dura mater, through which
      tension across sutures may regulate the rate of bone deposition in sutures.

PMID- 14962806
TI  - The relationship between muscle size and bone geometry during growth and in
      response to exercise.
AB  - As muscles become larger and stronger during growth and in response to increased
      loading, bones should adapt by adding mass, size, and strength. In this
      unilateral model, we tested the hypothesis that (1) the relationship between
      muscle size and bone mass and geometry (nonplaying arm) would not change during
      different stages of puberty and (2) exercise would not alter the relationship
      between muscle and bone, that is, additional loading would result in a similar
      unit increment in both muscle and bone mass, bone size, and bending strength
      during growth. We studied 47 competitive female tennis players aged 8-17 years.
      Total, cortical, and medullary cross-sectional areas, muscle area, and the polar
      second moment of area (I(p)) were calculated in the playing and nonplaying arms
      using magnetic resonance imaging (MRI); BMC was assessed by DXA. Growth effects:
      In the nonplaying arm in pre-, peri- and post-pubertal players, muscle area was
      linearly associated BMC, total and cortical area, and I(p) (r = 0.56-0.81, P <
      0.09 to < 0.001), independent of age. No detectable differences were found
      between pubertal groups for the slope of the relationship between muscle and bone
      traits. Post-pubertal players, however, had a higher BMC and cortical area
      relative to muscle area (i.e., higher intercept) than pre- and peri-pubertal
      players (P < 0.05 to < 0.01), independent of age; pre- and peri-pubertal players
      had a greater medullary area relative to muscle area than post-pubertal players
      (P < 0.05 to < 0.01). Exercise effects: Comparison of the side-to-side
      differences revealed that muscle and bone traits were 6-13% greater in the
      playing arm in pre-pubertal players, and did not increase with advancing
      maturation. In all players, the percent (and absolute) side-to-side differences
      in muscle area were positively correlated with the percent (and absolute)
      differences in BMC, total and cortical area, and I(p) (r = 0.36-0.40, P < 0.05 to
      < 0.001). However, the side-to-side differences in muscle area only accounted for
      11.8-15.9% of the variance of the differences in bone mass, bone size, and
      bending strength. This suggests that other factors associated with loading
      distinct from muscle size itself contributed to the bones adaptive response
      during growth. Therefore, the unifying hypothesis that larger muscles induced by
      exercise led to a proportional increase in bone mass, bone size, and bending
      strength appears to be simplistic and denies the influence of other factors in
      the development of bone mass and bone shape.

PMID- 14962807
TI  - Endothelin-1 down-regulates the expression of vascular endothelial growth factor
      A associated with osteoprogenitor proliferation and differentiation.
AB  - Endothelin-1 (ET-1) is implicated in the signaling between vascular endothelial
      cells (VECs) and osteoblasts during bone development, remodeling and repair.
      Vascular endothelial growth factor (VEGF) also plays an important role in these
      intercellular interactions. Our objectives were to identify which specific VEGF
      isoforms were produced during osteoblastic proliferation and differentiation and
      to determine the effects of ET-1 on VEGF mRNA and protein production by
      osteoblastic cells. Semiquantitative reverse transcription polymerase chain
      reaction (RT-PCR) and ELISA were used to evaluate VEGF mRNA isoform expression
      and protein synthesis at different stages of ET-1-induced osteoblastic
      differentiation in fetal rat calvaria (FRC) osteoblastic cells. Three VEGF mRNA
      isoforms were identified corresponding to VEGF(120), VEGF(164) and VEGF(188).
      Predominant isoforms VEGF(120) and VEGF(164) had a bimodal expression that
      increased in the early proliferation and late mineralization phases. ET-1
      stimulated osteoblastic proliferation and differentiation, but surprisingly, ET-1
      down-regulated VEGF mRNA and protein expression and sustained the down-regulation
      over time in long-term cultures. Time course studies showed that ET-1 inhibited
      VEGF mRNA expression after incubation for 3 h in 7- and 14-day FRC cell cultures.
      Similarly, ET-1 inhibited VEGF protein secretion by 5.8- and 2.8-fold in 7- and
      14-day FRC cells, respectively. VEGF-A protein secretion was inhibited by ET-1 in
      a dose-dependent manner with a maximal effect at 10(-7) M. This study supports a
      novel inhibitory role for ET-1 on VEGF synthesis in osteoblastic cells as a
      feedback mechanism in the temporal and spatial coupling of angiogenesis to bone
      formation and resorption.

PMID- 14962808
TI  - Regulation of pregnancy-associated plasma protein-A expression in cultured human
      osteoblasts.
AB  - Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase secreted by
      cultured human osteoblasts that has been implicated in the regulation of local
      insulin-like growth factor (IGF) bioavailability during bone growth and
      remodeling. However, very little is known about the regulation of PAPP-A
      expression in bone. In this study, we determined the effect of systemic and local
      osteoregulatory factors on PAPP-A mRNA and protein expression in normal human
      osteoblasts (hOB cells). Treatment of hOB cells with particular peptide growth
      factors (basic fibroblast growth factor, epidermal growth factor), steroid
      hormones (dexamethasone, 1,25-dihydroxyvitamin D(3)), and cytokines [interleukin
      6 (IL-6), IL-13, oncostatin M] with known involvement in bone cell physiology had
      no significant effect on PAPP-A expression. Agents that increase intracellular
      cyclic AMP (forskolin, prostaglandin E(2)) increased PAPP-A mRNA and protein
      expression approximately 3-fold. Tumor necrosis factor alpha (TNFalpha), IL
      1beta, and IL-4 also increased PAPP-A expression 3- to 4-fold. Transforming
      growth factor beta (TGFbeta) was previously shown to stimulate PAPP-A expression
      in hOB cells. The effects of TGFbeta, TNFalpha, and IL-1beta were additive,
      whereas the effects of TGFbeta and IL-4 were synergistic. In summary, TNFalpha,
      IL-1beta, and IL-4 were identified as potent stimulators of PAPP-A expression in
      primary cultures of human osteoblasts. These findings suggest a mechanism whereby
      cytokines present in bone and bone marrow could augment IGF bioavailability
      during skeletal growth and remodeling.

PMID- 14962810
TI  - Glucocorticoids induce glutamine synthetase expression in human osteoblastic
      cells: a novel observation in bone.
AB  - Glucocorticoids have marked effects on bone metabolism, and continued exposure of
      skeletal tissue to excessive amounts of these steroids results in osteoporosis.
      Therefore, in the present proteomic study, we characterized the potential effects
      of glucocorticoids on protein expression in human osteoblastic cells. Using two
      dimensional gel electrophoresis and mass spectrometry, we identified an increased
      expression of glutamine synthetase (GS) in dexamethasone (Dex)-treated human MG
      63 osteosarcoma cells. GS is an enzyme catalyzing the conversion of glutamate and
      ammonia to glutamine. Intracellular and extracellular glutamate levels may be
      important in cell signalling mediated by glutamate transporters and receptors
      which have recently been found in bone cells. The induction of GS protein by Dex
      was accompanied by an increase in mRNA level and enzyme activity. Dex induction
      of GS was also mediated by glucocorticoid receptors (GRs) because it was blocked
      by the GR antagonist RU-38486. In addition, Dex induction of GS expression was
      partially blocked by cyclohexamide indicating that it at least partly required
      new protein synthesis. GS induction by Dex was not associated with apoptosis as
      determined by Bax/Bcl-2 ratio and DNA staining. In addition to MG-63 cells, Dex
      induction of GS was also observed in human G-292 osteosarcoma cells as well as
      conditionally immortalized human preosteoblastic (HOB-03-C5) and mature
      osteoblastic (HOB-03-CE6) cells. However, in two other human osteosarcoma cell
      lines, SaOS-2 and U2-OS, GS expression was not affected by Dex. This observation
      may be explained by the lower levels of GR protein in these cells. In summary,
      this is the first report of the regulation of GS expression by glucocorticoids in
      bone cells. The role of GS in bone cell metabolism and glucocorticoid action on
      the skeleton is not yet known, but as a modulator of intracellular glutamate and
      glutamine levels, it may have an important role in these processes.

PMID- 14962809
TI  - MEPE has the properties of an osteoblastic phosphatonin and minhibin.
AB  - Matrix extracellular phosphoglycoprotein (MEPE) is expressed exclusively in
      osteoblasts, osteocytes and odontoblasts with markedly elevated expression found
      in X-linked hypophosphatemic rickets (Hyp) osteoblasts and in oncogenic
      hypophosphatemic osteomalacia (OHO) tumors. Because these syndromes are
      associated with abnormalities in mineralization and renal phosphate excretion, we
      examined the effects of insect-expressed full-length human-MEPE (Hu-MEPE) on
      serum and urinary phosphate in vivo, (33)PO(4) uptake in renal proximal tubule
      cultures and mineralization of osteoblast cultures. Dose-dependent
      hypophosphatemia and hyperphosphaturia occurred in mice following intraperitoneal
      (IP) administration of Hu-MEPE (up to 400 microg kg(-1) 31 h(-1)), similar to
      mice given the phosphaturic hormone PTH (80 microg kg(-1) 31 h(-1)). Also the
      fractional excretion of phosphate (FEP) was stimulated by MEPE [65.0% (P <
      0.001)] and PTH groups [53.3% (P < 0.001)] relative to the vehicle group [28.7%
      (SEM 3.97)]. In addition, Hu-MEPE significantly inhibited (33)PO(4) uptake in
      primary human proximal tubule renal cells (RPTEC) and a human renal cell line (Hu
      CL8) in vitro (V(max) 53.4% inhibition; K(m) 27.4 ng/ml, and V(max) 9.1%
      inhibition; K(m) 23.8 ng/ml, respectively). Moreover, Hu-MEPE dose dependently
      (50-800 ng/ml) inhibited BMP2-mediated mineralization of a murine osteoblast cell
      line (2T3) in vitro. Inhibition of mineralization was localized to a small (2
      kDa) cathepsin B released carboxy-terminal MEPE peptide (protease-resistant)
      containing the acidic serine-aspartate-rich motif (ASARM peptide). We conclude
      that MEPE promotes renal phosphate excretion and modulates mineralization.

PMID- 14962811
TI  - Relationship among densitometry, bone histomorphometry, and histologic stage in
      idiopathic myelofibrosis.
AB  - Idiopathic myelofibrosis (IMF) induces dramatic changes in bone. Bone remodeling
      and densitometric alterations in a series of nine patients with IMF and their
      relationship with the histologic stage of the disease were assessed. Patients
      were included at diagnosis and a bone marrow biopsy, dual-energy X-ray
      absorptiometry, and transiliac bone biopsy for histomorphometric analysis were
      performed. Five cases were classified as IMF histologic stage 1, one as stage 2,
      and three as stage 3. Compared with 40 age- and sex-matched controls, the
      following histomorphometric parameters were significantly higher in our patients:
      bone volume (BV/TV), osteoblast surface (Ob.S/BS), eroded surface (ES/BS),
      osteoclast surface (Oc.S/BS), osteoclast number (N.Oc/TA), mineralizing surface
      (MS/BS), reversal period (Rv.P), and remodeling period (Rm.P). Mineral apposition
      rate (MAR) and erosion depth (E.Depth) were significantly decreased (P < 0.05 for
      all comparisons). Bone mineral density (BMD) measurements showed high values for
      patient age and sex both at femur neck (Z score range +0.19 to +7) and total
      femur (Z score range -0.09 to +6.48). When densitometric values were analyzed
      according to IMF histologic stage, patients in stages 1 and 2 had significantly
      lower BMD values than to those in stage 3 (P = 0.024). In conclusion, patients
      with IMF present a characteristic bone histomorphometric pattern with increased
      bone volume and bone cells but low apposition and decreased erosion depth,
      suggesting a positive balance in bone remodeling units. This balance would
      produce the increase in bone mass observed in this disease. Given the increase in
      BMD observed with more advanced stages of IMF, this noninvasive method could be
      useful tool for assessing IMF progression.

PMID- 14962812
TI  - Mechanobiology of mandibular distraction osteogenesis: experimental analyses with
      a rat model.
AB  - We analyzed mechanobiological influences on successful distraction osteogenesis
      (DO). Mandibular distraction surgeries were performed on 15 adult male Sprague
      Dawley rats. Animals underwent gradual distraction (GD), progressive lengthening
      by small increments (5-day latency followed by 0.25 mm distractions twice daily
      for 8 days followed by 28-day maturation period). Distracted hemimandibles were
      harvested on postoperative days (POD) 5, 7, 10, 13, and 41. Load-displacement
      curves were then recorded for ex vivo distractions of 0.25 mm and stresses
      determined. Histologically, new bone formation appeared in GD specimens on
      distraction day 2 (POD 7), filling 50-60% of the gap by distraction day 8 (POD
      13), with nearly complete bony bridging at end maturation (POD 41). Average
      tensile strains imposed by each incremental distraction ranged from approximately
      10% to 12.5% during distraction days 2-8 and were associated with bone apposition
      rates of about 260 microm/day. Because this GD protocol was previously determined
      to be optimal for DO, we conclude that strains within this range provide an
      excellent environment for de novo bone apposition. Distraction caused tissue
      damage in distraction day 2, 5, and 8 specimens as evidenced by distinct drops in
      the load/displacement curves. Taken together, our interpretation of these data is
      that daily distractions cause daily tissue damage which triggers new mesenchymal
      tissue formation.

PMID- 14962813
TI  - Reduction in PINP, a marker of bone metabolism, with raloxifene treatment and its
      relationship with vertebral fracture risk.
AB  - In the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705
      postmenopausal women with osteoporosis, defined by low bone mineral density
      and/or prevalent vertebral fractures (VF), were randomized to placebo or
      raloxifene (60 or 120 mg/day). All women received daily calcium (500 mg) and
      vitamin D (400-600 IU) supplements. Our previous analyses found that changes in
      BMD and biochemical markers of bone turnover are poorly predictive of the
      reduction in VF risk observed with raloxifene. This present study evaluated the
      effects of raloxifene on type I procollagen N-terminal propeptide (PINP), a new
      marker of bone turnover. Logistic regression analysis models evaluated the
      relationships between the changes at 1 year in PINP, serum osteocalcin (OC), bone
      specific alkaline phosphatase (BSAP), and urinary excretion of type I collagen C
      telopeptide fragments normalized to creatinine (CTx/Cr), and the risk of new VF
      at 3 years for placebo and pooled raloxifene. A subset of 967 women (mean age =
      68 years) from the MORE cohort had PINP, OC, BSAP, and CTx evaluated at baseline.
      Both doses of raloxifene significantly decreased (P < 0.001) all biochemical
      markers of bone turnover from baseline. Compared to baseline, PINP levels were
      decreased by medians of 11.0% and 40.8% in the placebo and pooled raloxifene
      groups, respectively. In addition, the placebo and pooled raloxifene groups
      decreased serum OC by 8.5% and 31.8%, BSAP by 15.8% and 34.6%, and urinary CTx/Cr
      excretion by 5.6% and 46.5%, respectively, from baseline. In the pooled
      raloxifene group, the logistic regression relationship between 3-year VF risk and
      1-year percentage change for each biochemical marker was statistically
      significant with PINP (slope estimate = 0.0085, P = 0.009), OC (slope estimate =
      0.0068, P = 0.035), and BSAP (slope estimate = 0.0056, P = 0.039), but not with
      CTx/Cr (slope estimate = 0.0027, P = 0.192). Furthermore, the percent decrease in
      PINP at 1 year could account for 28% of the total reduction in vertebral fracture
      risk. In conclusion, a 1-year decrease in PINP, BSAP, or OC, but not CTx/Cr, may
      be predictive of the 3-year VF risk reduction with raloxifene therapy in this
      subset of postmenopausal women with osteoporosis.

PMID- 14962814
TI  - Discrimination between cases of hip fracture and controls is improved by hip
      structural analysis compared to areal bone mineral density. An ex vivo study of
      the femoral neck.
AB  - In vivo bone densitometry is affected by measurement inaccuracies arising from
      the assumptions made about soft tissue and marrow composition. This study tested
      the hypothesis that section modulus (SM, a measure of bending resistance) when
      measured ex vivo, would discriminate cases of hip fracture from controls better
      than areal bone mineral density (aBMD). The biopsies were from (n = 22, female)
      subjects that had suffered an intracapsular hip fracture. The control material (n
      = 24, female) was from post-mortem subjects. Serial peripheral quantitative
      computed tomography (pQCT) 1-mm thick cross-sectional images of femoral neck
      previously embedded in methacrylate were obtained with the Densiscan 1000 pQCT
      densitometer and matched for lateral location. The image voxels were converted to
      units of bone mass, which were then used to derive the section modulus. The data
      were used to derive means from which receiver operating characteristic (ROC)
      curves could be generated. The area under the curves (AUC) showed that
      discrimination between the fracture cases and controls was better for SM than
      aBMD [SM: AUC = 0.83 (95% confidence interval: 0.71, 0.96), aBMD: AUC = 0.70
      (0.54, 0.85); P = 0.034]. To simulate the forces experienced during a sideways
      fall, the model's neutral axis was rotated by 210 degrees. The results for
      section modulus were predictable from those at 0 degrees (r(2) = 0.97). We
      conclude that biomechanical analysis of the distribution of bone within the
      femoral neck may offer a marked improvement in the ability to discriminate
      patients with an increased risk of intracapsular fracture. Progress towards
      implementing this form of analysis in clinical densitometry should improve its
      diagnostic value, but may depend in part on better image resolution and more
      accurate corrections for the variability between subjects in regional soft tissue
      composition.

PMID- 14962815
TI  - Prevalence of vertebral fractures in French women older than 75 years from the
      EPIDOS study.
AB  - The aim of this study was to ascertain the prevalence and severity of vertebral
      fractures in French elderly women. We used spinal radiographs collected during
      the baseline examination of the Epidemiologie de l'Osteoporose (EPIDOS) study, a
      multicentric prospective study of risk factors for hip fracture. A total of 7598
      ambulatory women volunteers were recruited in the EPIDOS cohort using large
      population-based listings such as voter-registration lists. A subsample of 770
      participants were selected for spinal radiographs using a systematic selection
      procedure. Anteroposterior and lateral radiographs of the thoracic and lumbar
      spine were reviewed by two trained rheumatologists using the semiquantitative
      (SQ) method described by Genant et al. [J. Bone Miner Res. 8 (1993) 1137].
      Vertebral deformities that could be related to causes other than osteoporosis
      (i.e., Scheuermann's disease or osteoarthritis) were disregarded. The final
      analysis was made over 745 women after excluding 25 women whose spine radiographs
      were incomplete or of poor quality. The sample average age was 80.1 +/- 3.4
      years. Vertebral fractures were found in 170 women: 22.8% (95% CI, 19.8-25.8%). A
      single, two, three, or more vertebral fractures were seen in 99 (58.2%), 43
      (25.3%), and 28 (16.5%) of the 170 affected women, respectively. The prevalence
      of vertebral fractures increased with age from 19.0% (95% CI, 14.9-23.1%) among
      women 75-79 years old to 21.9% (95% CI, 17.3-26.5%) among those 80-84 years old
      and to 41.4%(95% CI, 31.0-51.7%) among those 85 years of age and over (Chi-square
      test for trend P < 0.00016). A significant correlation was found also between the
      number of vertebral fractures per woman and age (r = 0.108, P = 0.003) and
      between the spinal fracture index and age (r = 0.105, P = 0.004). We conclude
      that the prevalence of vertebral fractures is high in French ambulatory elderly
      women, which confirms the results of previous studies conducted in various
      Caucasian and Asian populations.

PMID- 14962816
TI  - Genetic approaches to assessing evidence for a T helper type 1 cytokine defect in
      adult asthma.
AB  - Recent evidence suggests that deficiency in the Th1 cytokine pathway may underlie
      the susceptibility to allergic asthma. This study examined whether (1) single
      nucleotide polymorphisms exist in the promoter region of the two interleukin (IL)
      12 subunit genes in patients with asthma; (2) messenger RNA and protein
      expressions of signal transducers and activators of transcription, IL-12, IFN
      gamma, and their receptors are altered in asthma; and (3) linkage to genes in the
      Th1 pathway is present in families with asthma in Iceland. The promoter regions
      of the IL-12 subunit genes were sequenced in 94 patients with asthma and 94
      control subjects without asthma. Linkage was examined in 169 families that
      included over 570 patients with asthma and 950 of their unaffected relatives. The
      results demonstrate no evidence of linkage to microsatellite markers in close
      association with genes within the Th1 pathway, and no polymorphism was detected
      in the promoter regions of the two IL-12 subunit genes in the cohort with asthma
      patients. Moreover, we found no differences in the messenger RNA or protein
      expression signals of genes in the IL-12 pathway between the patients and control
      subjects. We conclude that decrease in Th1 type cytokine response is unlikely to
      present a primary event in asthma.

PMID- 14962817
TI  - Single photon emission computed tomography of pulmonary emboli and venous thrombi
      using anti-D-dimer.
AB  - Previous attempts to diagnose thromboemboli using radiolabeled antibodies and
      nuclear medicine imaging have been disappointing. We present the results of
      experiments with intravenous technetium-99m-labeled deimmunized antifibrin Fab'
      fragments to diagnose thromboemboli using single photon emission computed
      tomography (SPECT), a highly sensitive scintigraphic imaging technique. Pulmonary
      emboli (PEs) and lower extremity deep vein thrombi (DVTs) were formed in five
      dogs, then technetium-99m-labeled Fab' ( approximately 400 mg, approximately 260
      MBq) were injected via forelimb veins. Thoracic and lower extremity SPECT scans
      were performed at 2-hour intervals after antibody infusion to visualize the
      thromboemboli. Four hours after antibody infusion, all PEs and DVTs of mass 0.4 g
      or greater were clearly visualized on SPECT scans as 'hot spots' within the lungs
      and legs, respectively. PEs (0.48 +/- 0.09 g) were intensely radiolabeled,
      yielding clot/blood radioactivity ratios of 22.8 +/- 5.6. DVTs (0.45 +/- 0.31 g)
      also had high clot/blood ratios (11.7 +/- 2.6). Infusion of these radiolabeled
      antibody fragments, combined with SPECT, produces clear images of PEs and DVTs
      within a clinically feasible time frame. The technique reliably identified even
      peripheral thromboemboli of relatively small size, which are difficult to
      diagnose with currently available imaging techniques, and may enable imaging of
      PEs, DVTs, or both in the same patient.

PMID- 14962818
TI  - Functional polymorphisms in the promoter region of macrophage migration
      inhibitory factor and atopy.
AB  - Macrophage migration inhibitory factor (MIF) is a pleiotrophic lymphocyte and
      macrophage cytokine; it is likely to play an important role in innate immunity.
      Genome-wide search for atopy susceptibility genes recently identified human
      chromosome 22q11, where the gene encoding MIF resides, as a region of interest
      for atopic traits. Both the -173G/C and -794 [CATT]5-8 repeat polymorphisms in
      the MIF promoter region are associated with altered levels of MIF gene
      transcription in vitro. We, therefore, hypothesized that these potentially
      functional polymorphisms may influence susceptibility to atopy and asthma. A case
      control analysis examined the genetic influence of these promoter polymorphisms
      on the development of atopy and asthma in a Japanese population (n = 584).
      Evidence for significant association between the -173G/C and -794 [CATT]5-8
      repeat polymorphisms and atopy was found; odds ratio for homozygotes of -173C
      allele was 3.67 (compared with homozygotes of -173G allele, 95% confidence
      interval = 1.43-9.46, p < 0.01), and odds ratio for noncarriers of the -794 [5
      CATT] allele was 3.51 (compared with 5-CATT repeat homozygotes, 95% confidence
      interval = 1.82-6.78, p < 0.0005). No associations with asthma were detected.
      These results indicate that promoter polymorphisms in the MIF promoter region are
      risk factors for atopy and implicate MIF in the pathogenesis of atopy in a
      Japanese population.

PMID- 14962819
TI  - Treatment of immature baboons for 28 days with early nasal continuous positive
      airway pressure.
AB  - Using the 125-day baboon model of long-term bronchopulmonary dysplasia, we
      hypothesized that early use of nasal continuous positive airway pressure (nCPAP),
      a noninvasive ventilatory method, combined with prophylactic surfactant therapy
      would permit continuation of alveolar and vascular development in the lung.
      Retrospective human studies have shown that infants treated with nCPAP spend less
      time on mechanical ventilation and thereby sustain less volutrauma. After
      delivery by cesarean section at 125 days (term, 185 days), the infants received
      two doses of surfactant (Curosurf) and daily caffeine citrate. Weaning from low
      volume positive pressure ventilation to nCPAP was attempted at 24 hours of age.
      Serial physiological parameters were recorded. Lung histopathology and
      morphometric measurements of nCPAP animals were done after necropsy at 28 days
      and data were compared with 125- and 156-day gestational controls. Documented
      episodes of clinical sepsis and pneumonia at postmortem examination were absent.
      nCPAP lungs showed enlarged thin-walled air spaces with minimal
      fibroproliferation and scattered secondary crests. Internal surface area and
      surface-to-volume ratio dimensions were similar to those of 156-day gestational
      control lungs, the intrauterine developmental control. nCPAP is an effective
      noninvasive ventilatory technique that minimizes lung injury in baboons at risk
      of developing bronchopulmonary dysplasia.

PMID- 14962820
TI  - Particulate matter exposure in cars is associated with cardiovascular effects in
      healthy young men.
AB  - Exposure to fine airborne particulate matter (PM(2.5)) is associated with
      cardiovascular events and mortality in older and cardiac patients. Potential
      physiologic effects of in-vehicle, roadside, and ambient PM(2.5) were
      investigated in young, healthy, nonsmoking, male North Carolina Highway Patrol
      troopers. Nine troopers (age 23 to 30) were monitored on 4 successive days while
      working a 3 P.M. to midnight shift. Each patrol car was equipped with air-quality
      monitors. Blood was drawn 14 hours after each shift, and ambulatory monitors
      recorded the electrocardiogram throughout the shift and until the next morning.
      Data were analyzed using mixed models. In-vehicle PM(2.5) (average of 24
      microg/m(3)) was associated with decreased lymphocytes (-11% per 10 microg/m(3))
      and increased red blood cell indices (1% mean corpuscular volume), neutrophils
      (6%), C-reactive protein (32%), von Willebrand factor (12%), next-morning heart
      beat cycle length (6%), next-morning heart rate variability parameters, and
      ectopic beats throughout the recording (20%). Controlling for potential
      confounders had little impact on the effect estimates. The associations of these
      health endpoints with ambient and roadside PM(2.5) were smaller and less
      significant. The observations in these healthy young men suggest that in-vehicle
      exposure to PM(2.5) may cause pathophysiologic changes that involve inflammation,
      coagulation, and cardiac rhythm.

PMID- 14962821
TI  - Pharmacokinetics of rifapentine at 600, 900, and 1,200 mg during once-weekly
      tuberculosis therapy.
AB  - The pharmacokinetics of rifapentine at 600, 900, and 1,200 mg were studied during
      once-weekly continuation phase therapy in 35 patients with tuberculosis. Mean
      area under the plasma concentration-time curve (AUC(0-infinity)) increased
      significantly with dose (rifapentine AUC(0- infinity): 296, 410, and 477
      microg.hour/ml at 600, 900, and 1,200 mg, respectively; p = 0.02 by linear
      regression). In multivariate stepwise regression analyses, AUC(0-infinity) values
      for rifapentine and the active 25-desacetyl metabolite were associated with drug
      dose and plasma albumin concentration, and were lower among men and among white
      individuals. Fifty-four percent of patients had total (free and protein-bound)
      plasma concentrations of rifapentine and of desacetyl rifapentine detected for
      more than 36 hours after clearance of concurrently administered isoniazid.
      Serious adverse effects of therapy in these study patients were infrequent (1 of
      35 cases; 3%) and not linked with higher rifapentine AUC(0-infinity) or peak
      concentration. The present pharmacokinetic study supports further trials to
      determine the optimal rifapentine dose for treatment of tuberculosis.

PMID- 14962823
TI  - Preoptic alpha 1- and alpha 2-noradrenergic agonists induce, respectively, PGE2
      independent and PGE2-dependent hyperthermic responses in guinea pigs.
AB  - We have shown previously that norepinephrine (NE) microdialyzed into the preoptic
      area (POA) of conscious guinea pigs stimulates local PGE(2) release. To identify
      the cyclooxygenase (COX) isozyme that catalyzes the production of this PGE(2) and
      the adrenoceptor (AR) subtype that mediates this effect, we microdialyzed for 6 h
      NE, cirazoline (alpha(1)-AR agonist), and clonidine (alpha(2)-AR agonist) into
      the POA of conscious guinea pigs pretreated intrapreoptically (intra-POA) with SC
      560 (COX-1 inhibitor) or nimesulide or MK-0663 (COX-2 inhibitors) and measured
      the animals' core temperature (T(c)) and intra-POA PGE(2) responses. Cirazoline
      induced T(c) rises promptly after the onset of its dialysis without altering
      PGE(2) levels. NE and clonidine caused early falls followed by late rises of
      T(c); intra-POA PGE(2) levels were closely correlated with this thermal course.
      COX-1 inhibition attenuated the clonidine-induced T(c) and PGE(2) falls but not
      the NE-elicited hyperthermia, but COX-2 inhibition suppressed both the clonidine-
      and NE-induced T(c) and PGE(2) rises. Coinfused cirazoline and clonidine
      reproduced the late T(c) rise of clonidine but not its early fall and also not
      the early rise produced by cirazoline; on the other hand, the PGE(2) responses
      were similar to those to NE. Prazosin (alpha(1)-AR antagonist) and yohimbine
      (alpha(2)-AR antagonist) blocked the effects of their respective agonists. These
      results indicate that alpha(1)- and alpha(2)-AR agonists microdialyzed into the
      POA of conscious guinea pigs evoke distinct T(c) responses: alpha(1)-AR
      activation produces quick, PGE(2)-independent T(c) rises, and alpha(2)-AR
      stimulation causes an early T(c) fall and a late, COX-2/PGE(2)-dependent T(c)
      rise.

PMID- 14962824
TI  - Effects of neuronal norepinephrine uptake blockade on baroreflex neural and
      peripheral arc transfer characteristics.
AB  - Neuronal uptake is the most important mechanism by which norepinephrine (NE) is
      removed from the synaptic clefts at sympathetic nerve terminals. We examined the
      effects of neuronal NE uptake blockade on the dynamic sympathetic regulation of
      the arterial baroreflex because dynamic characteristics are important for
      understanding the system behavior in response to exogenous disturbance. We
      perturbed intracarotid sinus pressure (CSP) according to a binary white noise
      sequence in anesthetized rabbits, while recording cardiac sympathetic nerve
      activity (SNA), arterial pressure (AP), and heart rate (HR). Intravenous
      administration of desipramine (1 mg/kg) decreased the normalized gain of the
      neural arc transfer function from CSP to SNA relative to untreated control (1.03
      +/- 0.09 vs. 0.60 +/- 0.08 AU/mmHg, mean +/- SE, P < 0.01) but did not affect
      that of the peripheral arc transfer function from SNA to AP (1.10 +/- 0.05 vs.
      1.08 +/- 0.10 mmHg/AU). The normalized gain of the transfer function from SNA to
      HR was unaffected (1.01 +/- 0.04 vs. 1.09 +/- 0.12 beats.min(-1).AU(-1)).
      Desipramine decreased the natural frequency of the transfer function from SNA to
      AP by 28.7 +/- 7.0% (0.046 +/- 0.007 vs. 0.031 +/- 0.002 Hz, P < 0.05) and that
      of the transfer function from SNA to HR by 64.4 +/- 2.2% (0.071 +/- 0.003 vs.
      0.025 +/- 0.002 Hz, P < 0.01). In conclusion, neuronal NE uptake blockade by
      intravenous desipramine administration reduced the total buffering capacity of
      the arterial baroreflex mainly through its action on the neural arc. The
      differential effects of neuronal NE uptake blockade on the dynamic AP and HR
      responses to SNA may provide clues for understanding the complex pathophysiology
      of cardiovascular diseases associated with neuronal NE uptake deficiency.

PMID- 14962825
TI  - Glucocorticoids influence brain glycogen levels during sleep deprivation.
AB  - We investigated whether glucocorticoids [i.e., corticosterone (Cort) in rats]
      released during sleep deprivation (SD) affect regional brain glycogen stores in
      34-day-old Long-Evans rats. Adrenalectomized (with Cort replacement; Adx+) and
      intact animals were sleep deprived for 6 h beginning at lights on and then
      immediately killed by microwave irradiation. Brain and liver glycogen and glucose
      and plasma glucose levels were measured. After SD in intact animals, glycogen
      levels decreased in the cerebellum and hippocampus but not in the cortex or brain
      stem. By contrast, glycogen levels in the cortex of Adx+ rats increased by 43% (P
      < 0.001) after SD, while other regions were unaffected. Also in Adx+ animals,
      glucose levels were decreased by an average of 28% throughout the brain after SD.
      Intact sleep-deprived rats had elevations of circulating Cort, blood, and liver
      glucose that were absent in intact control and Adx+ animals. Different responses
      between brain structures after SD may be due to regional variability in metabolic
      rate or glycogen metabolism. Our findings suggest that the elevated
      glucocorticoid secretion during SD causes brain glycogenolysis in response to
      energy demands.

PMID- 14962826
TI  - Homeostatic regulation of sleep in arrhythmic Siberian hamsters.
AB  - Sleep is regulated by independent yet interacting circadian and homeostatic
      processes. The present study used a novel approach to study sleep homeostasis in
      the absence of circadian influences by exposing Siberian hamsters to a simple
      phase delay of the photocycle to make them arrhythmic. Because these hamsters
      lacked any circadian organization, their sleep homeostasis could be studied in
      the absence of circadian interactions. Control animals retained circadian
      rhythmicity after the phase shift and re-entrained to the phase-shifted
      photocycle. These animals displayed robust daily sleep-wake rhythms with
      consolidated sleep during the light phase beginning about 1 h after light onset.
      This marked sleep-wake pattern was circadian in that it persisted in constant
      darkness. The distribution of sleep in the arrhythmic hamsters over 24 h was
      similar to that in the light phase of rhythmic animals. Therefore, daily sleep
      amounts were higher in arrhythmic animals compared with rhythmic ones. During 2-
      and 6-h sleep deprivations (SD), it was more difficult to keep arrhythmic
      hamsters awake than it was for rhythmic hamsters. Because the arrhythmic animals
      obtained more non-rapid eye movement sleep (NREMS) during the SD, they showed a
      diminished compensatory response in NREMS EEG slow-wave activity during recovery
      sleep. When amounts of sleep during the SD were taken into account, there were no
      differences in sleep homeostasis between experimental and control hamsters. Thus
      loss of circadian control did not alter the homeostatic response to SD. This
      supports the view that circadian and homeostatic influences on sleep regulation
      are independent processes.

PMID- 14962827
TI  - Extracellular norepinephrine reduces neuronal uptake of norepinephrine by
      oxidative stress in PC12 cells.
AB  - Cardiac norepinephrine (NE) uptake activity is reduced in congestive heart
      failure. Our studies in intact animals suggest that this effect on the cardiac
      sympathetic nerve endings is caused by oxidative stress and/or NE toxic
      metabolites derived from NE. In this study, we investigated the direct effects of
      NE on neuronal NE uptake activity and NE transporter (NET), using
      undifferentiated PC12 cells. Cells were incubated with NE (1-500 microM) either
      alone or in combination of Cu(2+) sulfate (1 microM), which promotes free radical
      formation by Fenton reaction for 24 h. NE uptake activity was measured using
      [(3)H]NE. Cell viability was determined with the use of Trypan blue exclusion and
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay, and cellular
      oxidative stress by dichlorodihydrofluorescein fluorescence and the GSH/GSSG
      ratio. Cell viability was reduced by NE >100 microM. At lower doses, NE produced
      oxidative stress and a dose-dependent reduction of NE uptake activity without
      affecting cell viability significantly. Cu(2+), which has no direct effect on NE
      uptake activity, potentiated oxidative stress and reduction of NE uptake activity
      produced by NE. This decrease of NE uptake activity was associated with
      reductions of NE uptake binding sites and NET protein expression by using the
      radioligand assay and Western blot analysis, but no changes in NET gene
      expression. In addition, the free-radical scavenger mannitol, and antioxidant
      enzymes superoxide dismutase and catalase, reduced oxidative stress and
      attenuated the reductions of NE uptake activity and NET protein produced by
      NE/Cu. Thus our results support a functional role of oxidative stress in
      mediating the neuronal NE uptake reducing effect of NE and that this effect of NE
      on NET is a posttranscriptional event.

PMID- 14962828
TI  - Insights into cardioprotection obtained from study of cellular Ca2+ handling in
      myocardium of true hibernating mammals.
AB  - Mammalian hibernators exhibit remarkable resistance to low body temperature,
      whereas non-hibernating (NHB) mammals develop ventricular dysfunction and
      arrhythmias. To investigate this adaptive change, we compared contractile and
      electrophysiological properties of left ventricular myocytes isolated from
      hibernating (HB) woodchucks (Marmota monax) and control NHB woodchucks. The major
      findings of this study were the following: 1) the action potential duration in HB
      myocytes was significantly shorter than in NHB myocytes, but the amplitude of
      peak contraction was unchanged; 2) HB myocytes had a 33% decreased L-type Ca2+
      current (I(Ca)) density and twofold faster I(Ca) inactivation but no change in
      the current-voltage relationship; 3) there were no changes in the density of
      inward rectifier K+ current, transient outward K+ current, or Na+/Ca2+ exchange
      current, but HB myocytes had increased sarcoplasmic reticulum Ca2+ content as
      estimated from caffeine-induced Na+/Ca2+ exchange current values; 4) expression
      of the L-type Ca2+ channel alpha(1C)-subunit was decreased by 30% in HB hearts;
      and 5) mRNA and protein levels of sarco(endo)plasmic reticulum Ca2+-ATPase 2a
      (SERCA2a), phospholamban, and the Na+/Ca2+ exchanger showed a pattern that is
      consistent with functional measurements: SERCA2a was increased and phospholamban
      was decreased in HB relative to NHB hearts with no change in the Na+/Ca2+
      exchanger. Thus reduced Ca2+ channel density and faster I(Ca) inactivation
      coupled to enhanced sarcoplasmic reticulum Ca2+ release may underlie shorter
      action potentials with sustained contractility in HB hearts. These changes may
      account for natural resistance to Ca2+ overload-related ventricular dysfunction
      and point to an important cardioprotective mechanism during true hibernation.

PMID- 14962829
TI  - Comparison of simultaneous measurement of mouse systolic arterial blood pressure
      by radiotelemetry and tail-cuff methods.
AB  - Radiotelemetry of mouse blood pressure accurately monitors systolic pressure,
      diastolic pressure, heart rate, and locomotor activity but requires surgical
      implantation. Noninvasive measurements of indirect systolic blood pressure have
      long been available for larger rodents and now are being reported more frequently
      for mice. This study compared mouse systolic arterial blood pressure measurements
      using implanted radiotelemetry pressure transducer with simultaneous tail-cuff
      measurements in the same unanesthetized mice. The pressure range for comparison
      was extended by inducing experimental hypertension or by observations of
      circadian elevations between 3 AM and 6 AM. Both trained and untrained tail-cuff
      operators used both instruments. Every effort was made to follow recommended
      manufacturer's instructions. With the initial flow-based tail-cuff instrument, we
      made 671 comparisons (89 sessions) and found the slope of the linear regression
      to be 0.118, suggesting poor agreement. In an independent assessment, 277
      comparisons (35 sessions) of radiotelemetry measurements with the pulse based
      tail-cuff instrument were made. The slope of the linear regression of the
      simultaneous measurements of systolic pressures was 0.98, suggesting agreement.
      Bland-Altman analysis also supported our interpretation of the linear regression.
      Thus although reliable systolic pressure measurements are possible with either
      tail-cuff or radiotelemetry techniques, in our hands some tail-cuff instruments
      fail to accurately detect elevated blood pressures. These data, however, do not
      distinguish whether this instrument-specific tail-cuff failure was due to
      operator or instrument inadequacies. We strongly advise investigators to obtain
      an independent and simultaneous validation of tail-cuff determinations of mouse
      blood pressure before making critical genotyping determinations.

PMID- 14962830
TI  - Ascorbic acid increases cardiovagal baroreflex sensitivity in healthy older men.
AB  - Cardiovagal baroreflex sensitivity (BRS) declines with advancing age in healthy
      men. We tested the hypothesis that oxidative stress contributes mechanistically
      to this age-associated reduction. Eight young (23 +/- 1 yrs, means +/- SE) and
      seven older (63 +/- 3) healthy men were studied. Cardiovagal BRS was assessed
      using the modified Oxford technique (bolus infusion of 50-100 microg sodium
      nitroprusside, followed 60 s later by a 100- to 150-microg bolus of phenylephrine
      hydrochloride) in triplicate at baseline and during acute intravenous ascorbic
      acid infusion. At baseline, cardiovagal BRS (slope of the linear portion of the R
      R interval-systolic blood pressure relation during pharmacological changes in
      arterial blood pressure) was 56% lower (P < 0.01) in older (8.3 +/- 1.6 ms/mmHg)
      compared with young (19.0 +/- 3.1 ms/mmHg) men. Ascorbic acid infusion increased
      plasma concentrations similarly in young (62 +/- 9 vs. 1,249 +/- 72 micromol/l
      for baseline and during ascorbic acid; P < 0.05) and older men (62 +/- 4 vs.
      1,022 +/- 55 micromol/l; P < 0.05) without affecting baseline blood pressure,
      heart rate, carotid artery compliance, or the magnitude of change in systolic
      blood pressure in response to bolus sodium nitroprusside and phenylephrine
      hydrochloride infusion. Ascorbic acid (vitamin C) infusion increased cardiovagal
      BRS in older (Delta58 +/- 16%; P < 0.01), but not younger (Delta - 4 +/- 4%) men.
      These data provide experimental support for the concept that oxidative stress
      contributes mechanistically to age-associated reductions in cardiovagal BRS in
      healthy men.

PMID- 14962831
TI  - Protein phosphatase 2A-mediated cross-talk between p38 MAPK and ERK in apoptosis
      of cardiac myocytes.
AB  - Mitogen-activated protein kinases (MAPKs) play different regulatory roles in
      signaling oxidative stress-induced apoptosis in cardiac ventricular myocytes. The
      regulation and functional role of cross-talk between p38 MAPK and extracellular
      signal-regulated kinase (ERK) pathways were investigated in cardiac ventricular
      myocytes in the present study. We demonstrated that inhibition of p38 MAPK with
      SB-203580 and SB-239063 enhanced H(2)O(2)-stimulated ERK phosphorylation, whereas
      preactivation of p38 MAPK with sodium arsenite reduced H(2)O(2)-stimulated ERK
      phosphorylation. In addition, pretreatment of cells with the protein phosphatase
      2A (PP2A) inhibitors okadaic acid and fostriecin increased basal and H(2)O(2)
      stimulated ERK phosphorylation. We also found that PP2A coimmunoprecipitated with
      ERK and MAPK/ERK (MEK) in cardiac ventricular myocytes, and H(2)O(2) increased
      the ERK-associated PP2A activity that was blocked by inhibition of p38 MAPK.
      Finally, H(2)O(2)-induced apoptosis was attenuated by p38 MAPK or PP2A
      inhibition, whereas it was enhanced by MEK inhibition. Thus the present study
      demonstrated that p38 MAPK activation decreases H(2)O(2)-induced ERK activation
      through a PP2A-dependent mechanism in cardiac ventricular myocytes. This
      represents a novel cellular mechanism that allows for interaction of two opposing
      MAPK pathways and fine modulation of apoptosis during oxidative stress.

PMID- 14962832
TI  - Endogenous beta3-adrenoreceptor activation contributes to left ventricular and
      cardiomyocyte dysfunction in heart failure.
AB  - The objective of the present study was to test the hypothesis that endogenous
      beta(3)-adrenoreceptor (AR) activation contributes to left ventricular (LV) and
      cardiomyocyte dysfunction in heart failure (CHF). Stimulation of the beta(3)-AR
      inhibits cardiac contraction. In the failing myocardium, beta(3)-ARs are
      upregulated, suggesting that stimulation of beta(3)-ARs may contribute to
      depressed cardiac performance in CHF. We assessed the functional significance of
      endogenous beta(3)-AR activation in 10 conscious dogs before and after pacing
      induced CHF. Under normal conditions, L-748,337, a specific beta(3)-AR
      antagonist, produced a mild increase in LV contractile performance assessed by
      the slope (E(es)) of the LV pressure-volume relation (18%, 6.2 +/- 0.9 vs. 7.3 +/
      1.2 mmHg/ml, P < 0.05) and the improved LV relaxation time constant (tau; 28.4
      +/- 1.9 vs. 26.8 +/- 1.0 ms, P < 0.05). After CHF, the plasma norepinephrine
      concentration increased eightfold, and L-748,337 produced a larger increase in
      E(es) (34%, 3.8 +/- 0.7 vs. 5.1 +/- 0.8 mmHg/ml, P < 0.05) and a greater decrease
      in tau (46.4 +/- 4.2 vs. 41.0 +/- 3.9 ms, P < 0.05). Similar responses were
      observed in isolated myocytes harvested from LV biopsies before and after CHF. In
      the normal myocyte, L-748,337 did not cause significant changes in contraction or
      relengthening. In contrast, in CHF myocytes, L-748,337 produced significant
      increases in contraction (5.8 +/- 0.9 vs. 6.8 +/- 0.9%, P < 0.05) and
      relengthening (33.5 +/- 4.2 vs. 39.7 +/- 4.0 microm/s, P < 0.05). The L-748,337
      induced myocyte response was associated with improved intracellular Ca(2+)
      concentration regulation. In CHF myocytes, nadolol caused a decrease in
      contraction and relengthening, and adding isoproterenol to nadolol caused a
      further depression of myocyte function. Stimulation of beta(3)-AR by endogenous
      catecholamine contributes to the depression of LV contraction and relaxation in
      CHF.

PMID- 14962833
TI  - Left atrial dilatation resulting from chronic mitral regurgitation decreases
      spatiotemporal organization of atrial fibrillation in left atrium.
AB  - Atrial conduction properties have been shown to differ among animal atrial
      fibrillation (AF) models of rapid atrial pacing (RAP), chronic mitral
      regurgitation (MR), and control. We hypothesized that these conduction
      differences would continue with the onset of AF, which would affect AF
      spatiotemporal organization, resulting in model-specific characteristics of AF.
      With frequency domain analysis of electrograms acquired from high-density optical
      mapping, AF from the right (RA) and left (LA) atrium in animals with RAP and MR
      were compared with control animals. At follow-up, the hearts were excised and
      perfused, and optical action potentials were recorded from a 2 x 2-cm area each
      of the RA and LA free wall with a 16 x 16 photodiode array. AF was induced with
      extra stimuli, several 2.4-s AF episodes were recorded in each dog, and a fast
      Fourier transform was calculated. The dominant frequency (DF) was determined, and
      the organization (organization index, OI) was calculated as the ratio of the area
      under the dominant peak and its harmonics to the total area of the spectrum. All
      possible pairs of electrograms for each episode were cross-correlated. LA AF in
      the chronic MR model showed an increase in the highest DF, the number of DF
      domains, and in frequency gradient compared with AF in control or RAP models. In
      addition, there was a decrease in OI and in the correlation coefficients in the
      LA of the MR model. These results suggest that the AF substrate in the MR model
      may be different from that of control or RAP models.

PMID- 14962834
TI  - Remodeling of resistance arteries in organoid culture is modulated by pressure
      and pressure pulsation and depends on vasomotion.
AB  - The hypothesis was tested that pressure and pressure pulsation modulate vascular
      remodeling. Arterioles ( approximately 200 microm lumen diameter) were dissected
      from rat cremaster muscle and studied in organoid culture. In the first series,
      arterioles were kept at a stable pressure level of either 50 or 100 mmHg for 3
      days. Both groups showed a progressive increase in myogenic tone during the
      experiment. Arterioles kept at 50 mmHg showed larger endothelium-dependent
      dilation, compared with vessels kept at 100 mmHg on day 3. Remodeling, as
      indicated by the reduction in maximally dilated diameter at 100 mmHg, was larger
      in arterioles kept at 50 mmHg compared with 100 mmHg: 34 +/- 4.5 versus 10 +/-
      4.8 microm (P < 0.05). In the second series, arterioles were subjected to a
      stable pressure of 60 mmHg or oscillating pressure of 60 +/- 10 mmHg (1.5 Hz) for
      4 days. Pressure pulsation induced partial dilation and was associated with less
      remodeling: 34 +/- 4.0 versus 19 +/- 4.5 microm (P < 0.01) for stable pressure
      versus oscillating pressure. Vasomotion was frequently observed in all groups,
      and inward remodeling was larger in vessels with vasomotion: 30 +/- 2.5 microm
      compared with vessels that did not exhibit vasomotion: 8.0 +/- 5.0 microm (P <
      0.01). In conclusion, these results indicate that remodeling is not enhanced by
      high pressure. Pressure pulsation causes partial dilation and reduces inward
      remodeling. The appearance of vasomotion is associated with enhanced inward
      remodeling.

PMID- 14962835
TI  - Flow-dependent increase of ICAM-1 on saphenous vein endothelium is sensitive to
      apamin.
AB  - The potassium channel blocker tetraethylammonium blocks the flow-induced increase
      in endothelial ICAM-1. We have investigated the subtype of potassium channel that
      modulates flow-induced increased expression of ICAM-1 on saphenous vein
      endothelium. Cultured human saphenous vein endothelial cells (HSVECs) or intact
      saphenous veins were perfused at fixed low and high flows in a laminar shear
      chamber or flow rig, respectively, in the presence or absence of potassium
      channel blockers. Expression of K(+) channels and endothelial ICAM-1 was measured
      by real-time polymerase chain reaction and/or immunoassays. In HSVECs, the
      application of 0.8 N/m(2) (8 dyn/cm(2)) shear stress resulted in a two- to
      fourfold increase in cellular ICAM-1 within 6 h (P < 0.001). In intact vein a
      similar shear stress, with pulsatile arterial pressure, resulted in a twofold
      increase in endothelial ICAM-1/CD31 staining area within 1.5 h (P < 0.001). Both
      increases in ICAM-1 were blocked by inclusion of 100 nM apamin in the vein
      perfusate, whereas other K(+) channel blockers were less effective. Two subtypes
      of small conductance Ca(2+)-activated K(+) channel (selectively blocked by
      apamin) were expressed in HSVECs and vein endothelium (SK3>SK2). Apamin blocked
      the upregulation of ICAM-1 on saphenous vein endothelium in response to increased
      flow to implicate small conductance Ca(2+)-activated K(+) channels in shear
      stress/flow-mediated signaling pathways.

PMID- 14962836
TI  - Effects of chronic psychosocial stress on cardiac autonomic responsiveness and
      myocardial structure in mice.
AB  - Repeated single exposures to social stressors induce robust shifts of cardiac
      sympathovagal balance toward sympathetic dominance both during and after each
      agonistic interaction. However, little evidence is available regarding possible
      persistent pathophysiological changes due to chronic social challenge. In this
      study, male CD-1 mice (n = 14) were implanted with a radiotelemetry system for
      electrocardiographic recordings. We assessed the effects of chronic psychosocial
      stress (15-day sensory contact with a dominant animal and daily 5-min defeat
      episodes) on 1) sympathovagal responsiveness to each defeat episode, as measured
      via time-domain indexes of heart rate variability (R-R interval, standard
      deviation of R-R interval, and root mean square of successive R-R interval
      differences), 2) circadian rhythmicity of heart rate across the chronic challenge
      (night phase, day phase, and rhythm amplitude values), and 3) amount of
      myocardial structural damage (volume fraction, density, and extension of
      fibrosis). This study indicated that there was habituation of acute cardiac
      autonomic responsiveness, i.e., the shift of sympathovagal balance toward
      sympathetic dominance was significantly reduced across repeated defeat episodes.
      Moreover, animals exhibited significant changes in heart rate rhythmicity, i.e.,
      increments in day and night values and reductions in the rhythm amplitude, but
      these were limited to the first 5 days of chronic psychosocial stress. The volume
      fraction of fibrosis was sixfold larger than in control animals, because of the
      appearance of many microscopic scarrings. In summary, although mice appeared to
      adapt to chronic psychosocial stress in terms of acute cardiovascular
      responsiveness and heart rate rhythmicity, structural alterations occurred at the
      myocardial level.

PMID- 14962837
TI  - Influence of the glia limitans on pial arteriolar relaxation in the rat.
AB  - We examined whether damage to the glia limitans (GL), via exposure to the
      gliotoxin l-alpha-aminoadipic acid (l-alphaAAA), alters hypercapnia-induced pial
      arteriolar dilation in vivo. Anesthetized female rats were prepared with closed
      cranial windows. Pial arteriolar diameters were measured using intravital
      microscopy. l-alphaAAA (2 mM) was injected into the space under the cranial
      windows 24 h before the study, and injury to the GL was confirmed by light
      microscopy. l-alphaAAA was associated with a reduction in pial arteriolar CO(2)
      reactivity to 40-50% of the level seen in vehicle-treated controls, with no
      further reduction in the CO(2) response after nitric oxide (NO) synthase (NOS)
      inhibition via N(omega)-nitro-l-arginine (l-NNA). Subsequent blockade of
      prostanoid synthesis, via indomethacin (Indo), reduced CO(2) reactivity to 10-15%
      of normal. In vehicle-treated controls, l-NNA, followed by Indo, reduced the
      response to approximately 50% and then to 15-20% of the normocapnic value,
      respectively. On the other hand, l-alphaAAA had no effect on vascular responses
      to the endothelium-dependent vasodilator acetylcholine or the NO donor SNAP and
      did not alter cortical somatosensory evoked responses. This indicates an absence
      of any direct l-alphaAAA actions on pial arterioles or influence on neuronal
      transmission. Furthermore, l-alphaAAA did not alter the vasodilation elicited by
      topical application of an acidic artificial cerebrospinal fluid solution,
      suggesting that the GL influences the pial arteriolar relaxation elicited by
      hypercapnic, but not local extracellular (EC), acidosis. That differences exist
      in the mechanisms mediating hypercapnia- versus EC acidosis-induced pial
      arteriolar dilations was further exemplified by the finding that topical
      application of a neuronal NOS (nNOS)-selective blocker (ARR-17477) reduced the
      response to hypercapnia (by approximately 65%) but not the response to EC
      acidosis. Disruption of GL gap junctional communication, using an antisense
      oligodeoxynucleotide (ODN) connexin43 knockdown approach, was accompanied by a
      33% lower CO(2) reactivity versus missense ODN-treated controls. These results
      suggest that the GL contribution to the hypercapnic vascular response appears to
      involve the NO-dependent component rather than the prostanoid-dependent component
      and may involve gap junctional communication. We speculate that the GL may act to
      facilitate the spread, to pial vessels, of hypercapnia-induced vasodilating
      signals arising in the comparatively few scattered nNOS neurons that lie well
      beneath the GL.

PMID- 14962838
TI  - Alterations of adenylyl cyclase and G proteins in aortocaval shunt-induced heart
      failure.
AB  - Unlike most other experimental models of congestive heart failure, the volume
      overload model induced by aortocaval shunt (AVS) in rats was found to exhibit
      enhanced beta-adrenoceptor (beta-AR) signaling. To study whether the adenylyl
      cyclase (AC)-G protein system is involved in such a change, we examined cardiac
      AC activity and protein content as well as G(s)alpha and G(i)alpha activities,
      protein contents, and mRNA levels in both left (LV) and right (RV) ventricles at
      the failing stage (16 wk after surgery). Basal and forskolin-stimulated AC
      activities were significantly increased in both LV and RV from the failing
      hearts; this change was associated with an upregulation of type V/VI AC protein.
      In contrast to 5'-guanylyl imidodiphosphate and NaF, the stimulatory effect of
      isoproterenol on AC was increased in the failing heart. Although G(s)alpha and
      G(i)alpha protein contents in the failing hearts were not altered, the mRNA level
      for G(s)alpha was decreased by 20% and that for G(i)alpha was increased by 20%.
      In addition, the activity of G(s)alpha, but not G(i)alpha, as assessed by toxin
      catalyzed ADP ribosylation, was significantly decreased in the failing heart.
      Losartan and imidapril treatments improved cardiac function and attenuated
      alterations in mRNA levels for G(s)alpha and G(i)alpha proteins, as well as
      G(s)alpha activity, without affecting changes in AC protein content or activities
      in heart failure due to volume overload. These data suggest that increased AC
      activity may contribute to the enhanced beta-AR signaling in the AVS model of
      heart failure, whereas alterations in gene expression for G proteins may be of an
      adaptive nature at this stage of heart failure.

PMID- 14962839
TI  - Suppression of electrical alternans by overexpression of HERG in canine
      ventricular myocytes.
AB  - Suppression of electrical alternans may be antiarrhythmic. Our previous computer
      simulations have suggested that increasing the rapid component of the delayed
      rectifier K(+) current (I(Kr)) suppresses alternans. To test this hypothesis,
      I(Kr) in isolated canine ventricular myocytes was increased by infection with an
      adenovirus containing the gene for the pore-forming domain of I(Kr) [human ether
      a-go-go gene (HERG)]. With the use of the perforated or whole cell patch-clamp
      technique, action potentials recorded at different pacing cycle lengths (CLs)
      were applied to the myocytes as the command waveforms. HERG infection markedly
      increased peak I(Kr) during the action potential (from 0.54 +/- 0.03 pA/pF in
      control to 3.60 +/- 0.81 pA/pF). Rate-dependent alterations of peak I(Kr) were
      similar for freshly isolated myocytes and HERG-infected myocytes. In both cell
      types, I(Kr) increased when CL decreased from 1,000 to 500 ms and then decreased
      progressively as CL decreased further. During alternans at CL = 170 ms, peak
      I(Kr) was larger for the short than for the long action potential for both
      groups, but the difference in peak I(Kr) was larger for HERG-infected myocytes.
      The voltage at which peak I(Kr) occurred was significantly less negative in HERG
      infected myocytes, in association with shifts of the steady-state voltage
      dependent activation and inactivation curves to less negative potentials. Pacing
      at short CL induced stable alternans in freshly isolated myocytes and in cultured
      myocytes without HERG infection, but not in HERG-infected myocytes. These data
      support the idea that increasing I(Kr) may be a viable approach to suppressing
      electrical alternans.

PMID- 14962840
TI  - A derivative-sigmoidal model reproduces operating point-dependent baroreflex
      neural arc transfer characteristics.
AB  - A cascade model comprised of a derivative filter followed by a nonlinear
      sigmoidal component reproduces the input size dependence of transfer gain in the
      baroreflex neural arc from baroreceptor pressure input to efferent sympathetic
      nerve activity (SNA). We examined whether the same model could predict the
      operating point dependence of the baroreflex neural arc transfer characteristics
      estimated by a binary white noise input. In eight anesthetized rabbits, we
      isolated bilateral carotid sinuses from the systemic circulation and controlled
      intracarotid sinus pressure (CSP). We estimated the linear transfer function from
      CSP to SNA while varying mean CSP among 70, 100, 130, and 160 mmHg (P(70),
      P(100), P(130), and P(160), respectively). The transfer gain at 0.01 Hz was
      significantly smaller at P(70) (0.61 +/- 0.26) and P(160) (0.60 +/- 0.25) than at
      P(100) (1.32 +/- 0.42) and P(130) (1.36 +/- 0.45) (in arbitrary units/mmHg; means
      +/- SD; P < 0.05). In contrast, transfer gain values above 0.5 Hz were similar
      among the protocols. As a result, the slope of increasing gain between 0.1 and
      0.5 Hz was significantly steeper at P(70) (17.6 +/- 3.6) and P(160) (14.1 +/-
      4.3) than at P(100) (8.1 +/- 4.4) and P(130) (7.4 +/- 6.6) (in dB/decade; means
      +/- SD; P < 0.05). These results were consistent with those predicted by the
      derivative-sigmoidal model, where the deviation of mean input pressure from the
      center of the sigmoidal nonlinearity reduced the transfer gain mainly in the low
      frequency range. The derivative-sigmoidal model functionally reproduces the
      dynamic SNA regulation by the arterial baroreflex over a wide operating range.

PMID- 14962841
TI  - P2Y purine receptor responses and expression in the pulmonary circulation of
      juvenile rabbits.
AB  - The purine nucleotide ATP mediates pulmonary vasodilation at birth by stimulation
      of P2Y purine receptors in the pulmonary circulation. The specific P2Y receptors
      in the pulmonary circulation and the segmental distribution of their responses
      remain unknown. We investigated the effects of purine nucleotides, ATP, ADP, and
      AMP, and pyrimidine nucleotides, UTP, UDP, and UMP, in juvenile rabbit pulmonary
      arteries for functional characterization of P2Y receptors. We also studied the
      expression of P2Y receptor subtypes in pulmonary arteries and the role of nitric
      oxide (NO), prostaglandins, and cytochrome P-450 metabolites in the response to
      ATP. In conduit size arteries, ATP, ADP, and AMP caused greater relaxation
      responses than UTP, UDP, and UMP. In resistance vessels, ATP and UTP caused
      comparable vasodilation. The response to ATP was attenuated by the P2Y antagonist
      cibacron blue, the NO synthase antagonist N(omega)-nitro-l-arginine methyl ester
      (l-NAME), and the cytochrome P-450 inhibitor 17-octadecynoic acid but not by the
      P2X antagonist alpha,beta-methylene ATP or the cyclooxygenase inhibitor
      indomethacin in conduit arteries. In the resistance vessels, l-NAME caused a more
      complete inhibition of the responses to ATP and UTP. Responses to AMP and UMP
      were NO and endothelium dependent, whereas responses to ADP and UDP were NO and
      endothelium independent in the conduit arteries. RT-PCR showed expression of
      P2Y(1), P2Y(2), and P2Y(4) receptors, but not P2Y(6) receptors, in lung
      parenchyma, pulmonary arteries, and pulmonary artery endothelial cells. These
      data suggest that distinct P2Y receptors mediate the vasodilator responses to
      purine and pyrimidine nucleotides in the juvenile rabbit pulmonary circulation.
      ATP appears to cause NO-mediated vasodilation predominantly through P2Y2
      receptors on endothelium.

PMID- 14962842
TI  - Gene transfer of a novel vasoactive natriuretic peptide stimulates cGMP and
      lowers blood pressure in mice.
AB  - Dendroaspis natriuretic peptide (DNP) is a recently described peptide produced by
      Dendroaspis angusticeps with structural and functional similarities to mammalian
      natriuretic peptides. These similarities suggest a potential role for DNP in
      cardiovascular therapeutics. To determine the physiological effects of chronic
      delivery of DNP, a gene transfer approach using first generation adenoviral
      vectors was utilized. Although the gene for DNP has not been cloned in any
      species, the peptide sequence in the snake is known. Preferred mammalian codons
      for snake DNP were cloned downstream of either the leader sequence (referred to
      as pBDNP-1) or prepropeptide sequence of human brain natriuretic peptide (BNP)
      cDNA (referred to as pBDNP-2). Transfections with pBDNP-1 or pBDNP-2 resulted in
      expected forms of chimeric DNP (cDNP) in cell lysates and conditioned media.
      Functional studies demonstrated the ability of both forms of cDNP within
      conditioned media to stimulate cGMP production in human vascular smooth muscle
      cells (hVSMC). Expressed cDNP inhibited hVSMC proliferation and stimulated
      vasorelaxation in a similar fashion. To investigate the chronic physiological
      effects of administration of cDNP, an adenoviral vector expressing cDNP (Ad-BDNP)
      was generated. Intravenous delivery of Ad-BDNP in mice resulted in dose-dependent
      systemic expression of cDNP. The highest level of expression was associated with
      consistent elevation of its presumed second messenger (cGMP) for 21 days but with
      transient lowering of systolic blood pressure in normotensive mice. This study
      demonstrates the biological features of the expression of the xenogenic peptide
      DNP.

PMID- 14962843
TI  - Localized transient increases in endothelial cell Ca2+ in arterioles in situ:
      implications for coordination of vascular function.
AB  - Intracellular Ca2+ transients were identified in endothelial cells (ECs) in
      intact blood-perfused arterioles. ECs in cremaster muscle arterioles (diameter
      approximately 45 microm) in anesthetized mice were loaded with the Ca2+ indicator
      fluo 4-AM by intraluminal perfusion, after which blood flow was reestablished.
      Confocal microscopy was used to visualize Ca2+ as a function of fluo-4 intensity
      in real time. Separate sets of experiments were performed under the following
      conditions: control, ischemia, during inhibition of P(2x) or P(1)
      purinoreceptors, and with the application of exogenous adenosine. In controls,
      spontaneous EC Ca2+ transients displayed a wide range of activity frequency (1-32
      events/min) and about one-third of these transient events were synchronized
      between adjacent ECs. The increase in Ca2+ remained localized and did not spread
      to encompass the entire cell body. Ca2+ transient activity decreased
      significantly with ischemia (from 9.9 +/- 0.6 to 3.1 +/- 0.3 events/min, n = 135)
      but was unaffected by P(2x) or P(1) receptor inhibition. Exogenous adenosine
      significantly increased the frequency of Ca2+ transients (to 12.8 +/- 0.9
      events/min) and increased synchronization so that 50% of all Ca2+ events were
      synchronized between ECs. This response to adenosine was not due to an increase
      in shear stress. These data indicate that localized Ca2+ transients are sensitive
      to flow conditions and, separately, to metabolically active pathways (exogenous
      adenosine), although the basal activity occurs independently of P(2x) or P(1)
      receptors. These transients may represent a mechanism by which individual EC
      responses are integrated to result in coordinated arteriolar responses in situ.

PMID- 14962844
TI  - The Na+/H+ exchanger isoform 2 is the predominant NHE isoform in murine colonic
      crypts and its lack causes NHE3 upregulation.
AB  - The Na(+)/H(+) exchanger isoform NHE2 is highly expressed in the intestinal
      tract, but its physiological role has remained obscure. The aim of this study was
      to define its expression, location, and regulatory properties in murine colon and
      to look for the compensatory changes in NHE2 (-/-) colon that allow normal
      histology and absorptive function. To this end, we measured murine proximal
      colonic surface and crypt cell NHE1, NHE2, and NHE3 expression levels, transport
      rates in response to acid, hyperosmolarity and cAMP in murine proximal colonic
      crypts, as well as changes in transcript levels and acid-activated NHE activity
      in NHE2 (-/-) crypts. We found that NHE2 was expressed most abundantly in crypts,
      NHE1 equally in crypts and surface cells, and NHE3 much stronger in surface
      cells. NHE2, like NHE1, was activated by low intracellular pH (pH(i)),
      hyperosmolarity, and cAMP, whereas NHE3 was activated only by low pH(i). Crypts
      isolated from NHE2 (-/-) mice displayed increased acid-activated NHE1- and NHE3
      attributable Na(+)/H(+) exchange activity, no change in NHE1 expression, and NHE3
      expression levels twice as high as in normal littermates. No change in cellular
      ultrastructure was found in NHE2 (-/-) colon. Our results demonstrate high NHE2
      expression in the crypts and suggest a role for NHE2 in cryptal pH(i) and volume
      homeostasis.

PMID- 14962845
TI  - Altered gene expression and increased bursting activity of colonic smooth muscle
      ATP-sensitive K+ channels in experimental colitis.
AB  - The ATP-sensitive K(+) channel (K(ATP)) is a complex composed of an inwardly
      rectifying, pore-forming subunit (Kir 6.1 and Kir 6.2) and the sulfonylurea
      receptor (SUR1 and SUR2). In gastrointestinal smooth muscle, these channels are
      important in regulating cell excitability. We examined the molecular composition
      of the K(ATP) channel in mouse colonic smooth muscle and determined its activity
      in the pathophysiological setting of experimental colitis. Following 7 days of
      dextran sulfate sodium (DSS) treatment in drinking water, colonic inflammation
      was scored by histology and physical signs. In whole cell recordings,
      levcromakalim-induced currents were significantly larger in inflamed cells. In
      cell-attached patch recordings of single-channel events, levcromakalim enhanced
      the bursting duration in inflamed cells. The single-channel conductance of
      approximately 42 pS was not altered with inflammation. mRNA for both Kir 6.1 and
      6.2 were detected by RT-PCR. Kir 6.1 was localized to the plasma membrane,
      whereas Kir 6.2 was mainly detected in the cytosol by immunohistochemistry.
      Quantitative PCR showed that Kir 6.1 gene expression was upregulated by almost 22
      fold, whereas SUR2B was downregulated by threefold after inflammation. Thus
      decreased motility of the colon during inflammation may be associated with
      changes in the transcriptional regulation of Kir 6.1 and SUR2B gene expression.

PMID- 14962846
TI  - Proapoptotic function of protein kinase CK2alpha" is mediated by a JNK signaling
      cascade.
AB  - Protein kinase CK2 (formerly casein kinase II) is a tetrameric enzyme
      constitutively expressed in all eurakyotic tissues that plays a significant role
      in the regulation of cell proliferation, malignant transformation, and apoptosis.
      The catalytic alpha-subunit of the enzyme is known to exist in three isoforms
      CK2alpha, CK2alpha' and CK2alpha". CK2alpha" is highly expressed in liver
      compared with other tissues and is required for the normal trafficking of several
      hepatocellular membrane proteins. Initial studies of dengue virus infection
      indicated that the CK2alpha"-deficient membrane trafficking mutant cell line
      (Trf1) was resistant to virus-induced cell death compared with the parental human
      hepatoma (HuH)-7 hepatoma line. Expression of recombinant CK2alpha" in Trf1 was
      capable of reverting this resistant phenotype. This study was extended to TNF
      alpha in addition to other stimuli of cell death in an attempt to uncover common
      death pathways that might be modulated by CK2alpha". Evaluation of different
      pathways involved in death signaling suggest that the regulation of a critical
      proapoptotic step in HuH-7 cells by CK2alpha" is mediated by a JNK signaling
      cascade.

PMID- 14962847
TI  - Glucagon-like peptide-2 induces intestinal adaptation in parenterally fed rats
      with short bowel syndrome.
AB  - Glucagon-like peptide-2 (GLP-2) is an intestinal trophic enteroendocrine peptide
      that is associated with intestinal adaptation following resection. Herein, we
      investigate the effects of GLP-2 in a total parenteral nutrition (TPN)-supported
      model of experimental short bowel syndrome. Juvenile Sprague-Dawley rats
      underwent a 90% small intestinal resection and jugular catheter insertion. Rats
      were randomized to three groups: enteral diet and intravenous saline infusion,
      TPN only, or TPN + 10 microg.kg(-1).h(-1) GLP-2. Nutritional maintenance was
      isocaloric and isonitrogenous. After 7 days, intestinal permeability was assessed
      by quantifying the urinary recovery of gavaged carbohydrate probes. The following
      day, animals were euthanized, and intestinal tissue was processed for
      morphological and crypt cell proliferation (CCP) analysis, apoptosis (caspase-3),
      and expression of SGLT-1 and GLUT-5 transport proteins. TPN plus GLP-2 treatment
      resulted in increased bowel and body weight, villus height, intestinal mucosal
      surface area, CCP, and reduced intestinal permeability compared with the TPN
      alone animals (P < 0.05). GLP-2 treatment induced increases in serum GLP-2 levels
      and intestinal SGLT-1 expression (P < 0.01) compared with either TPN or enteral
      groups. No differences were seen in the villus apoptotic index between resection
      groups. Enterally fed resected animals had a significant decrease in crypt
      apoptotic indexes compared with nontreated animals. This study demonstrates that
      GLP-2 alone, without enteral feeding, stimulates indexes of intestinal
      adaptation. Secondly, villus hypertrophy associated with adaptation was
      predominantly due to an increase in CCP and not to changes in apoptotic rates.
      Further studies are warranted to establish the mechanisms of action and
      therapeutic potential of GLP-2.

PMID- 14962848
TI  - Intestinal motor disorders associated with cyclical bacterial overgrowth in a rat
      model of enteritis.
AB  - The aims of this study were: 1) to obtain an experimental model reproducing the
      characteristics of chronicity and spontaneous relapses found in inflammatory
      bowel disease (IBD) and 2) to correlate these changes with intestinal motility
      and bacteria translocation. For this purpose, two groups of Sprague-Dawley rats
      were used: a treated group that received two subcutaneous injections of
      indomethacin (7.5 mg/kg) 48 h apart and a control group that received saline.
      Blood leukocytes, TNF, and fecal parameters were monitored for 90 days after
      treatment. In treated rats, a cyclic oscillation of blood leukocytes and TNF
      concomitant with an inverse correlation of fecal output was observed. Treated
      rats were then selected either during their highest or lowest blood leukocyte
      values for motor activity and microbiological evaluation. Controls were obtained
      in age-matched rats. Rats with high leukocyte levels showed a decrease of motor
      activity. In contrast, animals with low leukocyte levels presented hypermotility.
      Bacterial overgrowth accompanied by bacterial translocation was found in the
      group with high leukocytes, whereas no differences were observed between the
      control and indomethacin groups during the lowest leukocyte phase. We obtained a
      model of IBD characterized by a chronic cyclic oscillation of intestinal
      motility, flora, and inflammatory blood parameters. During the high-leukocyte
      stage, motor activity decrease is related to bacterial translocation. This phase
      is followed by a reactive one characterized by hypermotility associated with a
      decrease in both bacterial growth and leukocytes. However, as in IBD, this
      reaction seems unable to prevent a return to relapse.

PMID- 14962849
TI  - Endothelial nitric oxide synthase is protective in the initiation of caerulein
      induced acute pancreatitis in mice.
AB  - The effect of inhibiting nitric oxide (NO) synthase (NOS) or enhancing NO on the
      course of acute pancreatitis (AP) is controversial, in part because three NOS
      isoforms exist: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). We
      investigated whether inhibition or selective gene deletion of NOS isoforms
      modified the initiation phase of caerulein-induced AP in mice and explored
      whether this affected pancreatic microvascular blood flow (PMBF). We investigated
      the effects of nonspecific NOS inhibition with N(omega)-nitro-l-arginine (l-NNA;
      10 mg/kg ip) or targeted deletion of eNOS, nNOS, or iNOS genes on the initiation
      phase of caerulein-induced AP in mice using in vivo and in vitro models. Western
      blot analysis was performed to assess eNOS phosphorylation status, an indicator
      of enzyme activity, and microsphere studies were used to measure PMBF. l-NNA and
      eNOS deletion, but not nNOS or iNOS deletion, increased pancreatic trypsin
      activity and serum lipase during the initiation phase of in vivo caerulein
      induced AP. l-NNA and eNOS did not affect trypsin activity in caerulein
      hyperstimulated isolated acini, suggesting that nonacinar events mediate the
      effect of NOS blockade in vivo. The initiation phase of AP in wild-type mice was
      associated with eNOS Thr(495) residue dephosphorylation, which accompanies eNOS
      activation, and a 178% increase in PMBF; these effects were absent in eNOS
      deleted mice. Thus eNOS is the main isoform influencing the initiation of
      caerulein-induced AP. eNOS-derived NO exerts a protective effect through actions
      on nonacinar cell types, most likely endothelial cells, to produce greater PMBF.

PMID- 14962850
TI  - Where are we now with hormone replacement therapy?

PMID- 14962851
TI  - Thalassaemia major: the murky story of deferiprone.

PMID- 14962852
TI  - Discrete choice experiments in health care.

PMID- 14962853
TI  - Facing up to surgical deaths.

PMID- 14962856
TI  - Government task force needed to tackle obesity.

PMID- 14962858
TI  - Smoking is causing impotence, miscarriages, and infertility.

PMID- 14962861
TI  - Controversial disease dropped from Prozac product information.

PMID- 14962863
TI  - South African health service must strengthen infection control measures.

PMID- 14962866
TI  - Cigarette packs to feature graphic images.

PMID- 14962868
TI  - Gulf war syndrome case collapses.

PMID- 14962871
TI  - Mortality from avian flu is higher than in previous outbreak.

PMID- 14962873
TI  - Acute stroke units and early CT scans are linked to lower in-hospital mortality
      rates.

PMID- 14962875
TI  - Variations and increase in use of statins across Europe: data from administrative
      databases.

PMID- 14962874
TI  - Benefits and harms associated with hormone replacement therapy: clinical decision
      analysis.
AB  - OBJECTIVE: To evaluate harms and benefits associated with use of combined hormone
      replacement therapy (HRT) for five years in women with different baseline risks
      for breast cancer. DESIGN: Probabilistic clinical decision analysis. SETTING:
      Hypothetical population of white UK women aged 50 years with different baseline
      risks for breast cancer. MAIN OUTCOME MEASURE: Gain or loss in quality adjusted
      life years (QALYs). RESULTS: Women free of menopausal symptoms showed a net harm
      from HRT use, which increased for increasing baseline risk of breast cancer.
      Those with a baseline risk of 1.2% would expect a loss in QALYs of 0.4 months (-
      0.03 QALYs, 95% credibility interval - 0.05 to - 0.01). The main analysis showed
      HRT to be on average beneficial in women with symptoms, with benefit decreasing
      with increasing baseline risk of breast cancer. The results were sensitive to the
      assumed value of quality of life with menopausal symptoms, therefore a contour
      plot was developed to show the probability of net harm for a range of different
      values and baseline risks. CONCLUSIONS: HRT for primary prevention of chronic
      diseases in women without menopausal symptoms is unjustified. Perceived quality
      of life in women with symptoms should be taken into account when deciding on HRT.
      Thus, a decision analysis tailored to an individual woman is more appropriate in
      clinical practice than a population based approach.

PMID- 14962876
TI  - Prevalence of asthma and allergy in schoolchildren in Belmont, Australia: three
      cross sectional surveys over 20 years.

PMID- 14962877
TI  - Biofeedback for pelvic floor dysfunction in constipation.

PMID- 14962878
TI  - ABC of smoking cessation. Use of simple advice and behavioural support.

PMID- 14962879
TI  - Paying for statins.

PMID- 14962880
TI  - Paying to choose.

PMID- 14962881
TI  - Treating inguinal hernias: ...and is misleading.

PMID- 14962882
TI  - Objective assessment of technical skills in surgery: assessment should include
      decision making.

PMID- 14962883
TI  - Treating inguinal hernias: editorial does not tell the whole story...

PMID- 14962884
TI  - Objective assessment of technical skills in surgery: surgical skills and facts
      may be best taught in non-clinical training modules.

PMID- 14962885
TI  - Prevention of coronary heart disease: statins are even less effective than paper
      shows.

PMID- 14962886
TI  - Prevention of coronary heart disease: incremental cost effectiveness raises
      issues.

PMID- 14962887
TI  - Prevention of coronary heart disease: data in table 2 could be shown more
      explicitly for better understanding.

PMID- 14962888
TI  - Prevention of coronary heart disease: is a cure too expensive?

PMID- 14962889
TI  - Payment for coroners' postmortem examinations: ...and not part of the equation.

PMID- 14962890
TI  - Omega 3 fatty acids and cardiovascular disease: algae can be source of "fish"
      oil.

PMID- 14962891
TI  - Omega 3 fatty acids and cardiovascular disease: plant sources may be as effective
      as oily fish.

PMID- 14962892
TI  - Payment for coroners' postmortem examinations: financial gain is pathetic...

PMID- 14962893
TI  - Doctors are tending to be perceived as inherently bad.

PMID- 14962895
TI  - Making Amends misses the point.

PMID- 14962896
TI  - Infection of mature monocyte-derived dendritic cells with human cytomegalovirus
      inhibits stimulation of T-cell proliferation via the release of soluble CD83.
AB  - We have studied the mechanisms by which human cytomegalovirus (HCMV) infection of
      monocyte-derived dendritic cells (moDCs) contribute to immune suppression. Unlike
      infection of immature moDCs, infection of mature moDCs is not lytic and results
      in minimally decreased surface major histocompatibility complex (MHC) and
      costimulatory molecule expression. The presence of a small percentage of CMV
      infected mature moDCs, or the transfer of supernatant from infected moDCs
      depleted of infectious virions, is nevertheless sufficient to cause marked
      inhibition of immunostimulation by normal uninfected moDCs. Neither viral nor
      human interleukin 10 (IL-10) nor transforming growth factor-beta-1 (TGF-beta-1)
      could account for this inhibition. In contrast, we show that infected mature
      moDCs lose surface CD83 while maintaining intracellular protein expression.
      Soluble CD83 accumulates in the supernatants of CMV-infected mature moDCs, and
      CD83 immunodepletion removes the inhibitory effect of these supernatants on
      normal DC immunostimulation. We have thus discovered a new mechanism by which
      HCMV infection may establish a nonlytic reservoir in mature moDCs that inhibits
      DC-mediated T-cell responses.

PMID- 14962897
TI  - Chronic lymphocytic leukemia: revelations from the B-cell receptor.
AB  - The finding that chronic lymphocytic leukemia (CLL) consists of 2 clinical
      subsets, distinguished by the incidence of somatic mutations in the
      immunoglobulin (Ig) variable region (V) genes, has clearly linked prognosis to
      biology. Antigen encounter by the cell of origin is indicated in both subsets by
      selective but distinct expression of V genes, with evidence for continuing
      stimulation after transformation. The key to distinctive tumor behavior likely
      relates to the differential ability of the B-cell receptor (BCR) to respond. Both
      subsets may be undergoing low-level signaling in vivo, although analysis of blood
      cells limits knowledge of critical events in the tissue microenvironment.
      Analysis of signal competence in vitro reveals that unmutated CLL generally
      continues to respond, whereas mutated CLL is anergized. Differential
      responsiveness may reflect the increased ability of post-germinal center B cells
      to be triggered by antigen, leading to long-term anergy. This could minimize cell
      division in mutated CLL and account for prognostic differences. Unifying features
      of CLL include low responsiveness, expression of CD25, and production of
      immunosuppressive cytokines. These properties are reminiscent of regulatory T
      cells and suggest that the cell of origin of CLL might be a regulatory B cell.
      Continuing regulatory activity, mediated via autoantigen, could suppress Ig
      production and lead to disease-associated hypogammaglobulinemia.

PMID- 14962898
TI  - The peripheral benzodiazepine receptor ligand PK11195 overcomes different
      resistance mechanisms to sensitize AML cells to gemtuzumab ozogamicin.
AB  - The antibody-targeted therapeutic, gemtuzumab ozogamicin (GO, Mylotarg), is
      approved for treatment of relapsed acute myeloid leukemia (AML). We previously
      showed that AML blasts from GO refractory patients frequently express the drug
      transporters P-glycoprotein (Pgp) and/or multidrug resistance protein (MRP). We
      also previously reported that inhibition of drug transport by the Pgp modulator,
      cyclosporine A (CSA), can increase GO sensitivity in Pgp(+) AML cells and that
      the peripheral benzodiazepine receptor ligand, PK11195, sensitizes AML cells to
      standard chemotherapeutics both by inhibiting Pgp-mediated efflux and by
      promoting mitochondrial apoptosis. We now show that PK11195 also can overcome
      multiple resistance mechanisms to increase GO sensitivity in AML cells, including
      resistance associated with expression of drug transporters and/or antiapoptotic
      proteins. PK11195 substantially increases GO cytotoxicity in AML cells from many
      different cell lines and primary patient samples, often more effectively than
      CSA. We also show that PK11195 is nontoxic in NOD/SCID mice and can sensitize
      xenografted human AML cells to GO. Since PK11195 is well tolerated in humans as a
      single agent, its further study as a multifunctional chemosensitizer for anti-AML
      therapies, including GO-based therapies, is warranted.

PMID- 14962899
TI  - Probiotic effects on experimental graft-versus-host disease: let them eat yogurt.
AB  - Acute graft-versus-host disease (aGVHD) often limits feasibility and outcome of
      allogeneic bone marrow transplantation. Current pathophysiologic concepts of
      aGVHD involve conditioning regimens, donor-derived T cells, proinflammatory
      cytokines, and bacterial lipopolysaccharide (LPS) as a major trigger for aGVHD.
      LPS derives mostly from gram-negative bacteria and can enter circulation through
      the impaired mucosal barrier after the conditioning regimen. Probiotic
      microorganisms have been shown to alter the composition of the intestinal
      microflora and thereby mediate anti-inflammatory effects. We hypothesized that
      modifying the enteric flora using the probiotic microorganism Lactobacillus
      rhamnosus GG, would ameliorate aGVHD. Here we show that oral administration of
      Lactobacillus rhamnosus GG before and after transplantation results in improved
      survival and reduced aGVHD. Furthermore, subculturing of mesenteric lymph node
      tissue revealed a reduced translocation of enteric bacteria. Our findings suggest
      that alteration of the intestinal microflora plays an important role in the
      initiation of experimental aGVHD.

PMID- 14962900
TI  - CD34+CD38- hematopoietic precursors derived from human embryonic stem cells
      exhibit an embryonic gene expression pattern.
AB  - Gene expression patterns of CD34(+)CD38(-) cells derived from human embryonic
      stem cells (ESCs) were compared with those of cells isolated from adult human
      bone marrow (BM) using microarrays; 1692 and 1494 genes were expressed at levels
      at least 3-fold above background in cells from BM and ESCs, respectively. Of
      these, 494 showed similar levels of expression in cells from both sources, 791
      genes were overexpressed in cells from BM (BM versus ESCs, at least 2-fold), and
      803 genes were preferentially expressed in cells from ESCs (ESCs versus BM, at
      least 2-fold). The message of the flt-3 gene was markedly decreased in cells from
      ESCs, whereas there was substantial flt-3 expression in cells from BM. High
      levels of embryonic epsilon-globin expression were observed-but no adult beta
      globin message-in CD34(+)CD38(-) cells from ESCs, whereas high levels of beta
      globin expression-but no embryonic epsilon-globin message-could be detected in
      cells from BM. Furthermore, high levels of major histocompatibility complex (MHC)
      gene expression were demonstrated in cells from BM but very low levels of MHC
      message in corresponding cells from ESCs. These observations demonstrate that
      CD34(+)CD38(-) cells derived from ESCs correspond consistently to an early
      developmental stage at which the yolk sac and fetal liver are the primary sites
      of hematopoiesis.

PMID- 14962901
TI  - Hoxb4-deficient mice undergo normal hematopoietic development but exhibit a mild
      proliferation defect in hematopoietic stem cells.
AB  - Enforced expression of Hoxb4 dramatically increases the regeneration of murine
      hematopoietic stem cells (HSCs) after transplantation and enhances the
      repopulation ability of human severe combined immunodeficiency (SCID)
      repopulating cells. Therefore, we asked what physiologic role Hoxb4 has in
      hematopoiesis. A novel mouse model lacking the entire Hoxb4 gene exhibits
      significantly reduced cellularity in spleen and bone marrow (BM) and a subtle
      reduction in red blood cell counts and hemoglobin values. A mild reduction was
      observed in the numbers of primitive progenitors and stem cells in adult BM and
      fetal liver, whereas lineage distribution was normal. Although the cell cycle
      kinetics of primitive progenitors was normal during endogenous hematopoiesis,
      defects in proliferative responses of BM Lin(-) Sca1(+) c-kit(+) stem and
      progenitor cells were observed in culture and in vivo after the transplantation
      of BM and fetal liver HSCs. Quantitative analysis of mRNA from fetal liver
      revealed that a deficiency of Hoxb4 alone changed the expression levels of
      several other Hox genes and of genes involved in cell cycle regulation. In
      summary, the deficiency of Hoxb4 leads to hypocellularity in hematopoietic organs
      and impaired proliferative capacity. However, Hoxb4 is not required for the
      generation of HSCs or the maintenance of steady state hematopoiesis.

PMID- 14962902
TI  - Mutations in the ELA2 gene correlate with more severe expression of neutropenia:
      a study of 81 patients from the French Neutropenia Register.
AB  - Heterozygous mutations of the gene encoding neutrophil elastase (ELA2) have been
      associated with cyclic neutropenia (CN) and severe congenital neutropenia (SCN).
      To date, 30 different mutations have been reported, but no correlation has been
      found with the degree of neutropenia. To address this issue, we analyzed the
      clinical, hematologic, and molecular characteristics of 81 unrelated patients
      with SCN (n = 54) or CN (n = 27). We identified mutations in 31 patients, two
      thirds of whom had sporadic forms. Familial cases were consistent with dominant
      inheritance. Seventeen novel mutations were identified, showing that the
      mutational spectrum encompasses not only the region encoding the mature enzyme
      but also the prodomains and promoter region. Genotype-phenotype analysis strongly
      suggested that ELA2 mutations correlate with more severe expression of
      neutropenia, specifically in patients diagnosed with SCN. This study underlines
      the importance of ELA2 molecular screening to identify patients who may be at
      particular risk of severe bacterial infections and/or acute myeloid
      leukemia/myelodysplasia. By phenotypic analysis of affected relatives and
      carriers of the same ELA2 mutations, we showed that the expression of neutropenia
      in CN and SCN may be either homogeneous or variable according to the type of
      mutations, suggesting different pathogenetic mechanisms.

PMID- 14962903
TI  - Immunoglobulin class-switch recombination in mice devoid of any S mu tandem
      repeat.
AB  - Immunoglobulin heavy-chain class-switch recombination (CSR) occurs between highly
      repetitive switch sequences located upstream of the constant region genes.
      However, the role of these sequences remains unclear. Mutant mice were generated
      in which most of the I mu -- C mu intron was deleted, including all the repeats.
      Late B-cell development was characterized by a severe impairment, but not a
      complete block, in class switching to all isotypes despite normal germ line
      transcription. Sequence analysis of the I mu -- C mu intron in in vitro activated
      mutant splenocytes did not reveal any significant increase in activation-induced
      cytidine deaminase (AID)-induced somatic mutations. Analysis of switch junctions
      showed that, in the absence of any S mu repeat, the Imicro exon was readily used
      as a substrate for CSR. In contrast to the sequence alterations downstream of the
      switch junctions, very few, if any, mutations were found upstream of the junction
      sites. Our data suggest that the core E mu enhancer could be the boundary for CSR
      associated somatic mutations. We propose that the core E mu enhancer plays a
      central role in the temporal dissociation of somatic hypermutation from class
      switching.

PMID- 14962904
TI  - Low dendritic cell count after allogeneic hematopoietic stem cell transplantation
      predicts relapse, death, and acute graft-versus-host disease.
AB  - Dendritic cells (DCs) are key antigen-presenting cells with a potential role in
      tumor vaccines. We investigated the hypothesis that early reconstitution of DCs
      after allogeneic hematopoietic stem cell transplantation (SCT) improves survival.
      We also correlated DC reconstitution with complications of relapse and acute
      graft-versus-host disease (aGVHD). Fifty patients underwent transplantation
      between February 2000 and March 2003, with a median follow-up of 501 days (range,
      136-1263 days). Most (92%) received blood stem cells, and the remainder received
      bone marrow from HLA-matched sibling donors for predominantly high-risk
      hematologic malignancies. Around the time of engraftment, peripheral blood
      underwent flow cytometry analysis for DCs, and the cells were divided as DC1 and
      DC2. Using Kaplan-Meier analysis, patients with lower DC counts (< 4.97
      cells/microL) were found to have significantly worse survival (P =.002),
      increased incidence of relapse (P =.002), higher incidence of aGVHD onset (P
      =.0005), and a composite end point of relapse or death (P =.0017). A Cox
      proportional hazards multivariate model adjusted for important covariates
      confirmed that low DC count is independently associated with death (hazard ratio
      [HR], 3.8; P =.02), time to relapse (HR, 11.6; P =.001), and aGVHD (HR, 3.3; P
      =.04). Sensitivity and specificity rates for low DC count in predicting death or
      relapse are 73% and 75%, respectively. Low numbers of circulating DCs
      significantly increase the risk for relapse and acute GVHD and predict death
      after allogeneic SCT.

PMID- 14962905
TI  - Engraftment of NOD/SCID-beta2 microglobulin null mice with multilineage
      neoplastic cells from patients with myelodysplastic syndrome.
AB  - The development of immunodeficient mouse xenograft models has greatly facilitated
      the investigation of some human hematopoietic malignancies, but application of
      this approach to the myelodysplastic syndromes (MDSs) has proven difficult. We
      now show that cells from most MDS patients (including all subtypes) repopulate
      nonobese diabetic-severe combined immunodeficient (scid)/scid-beta2 microglobulin
      null (NOD/SCID-beta2m(-/-)) mice at least transiently and produce abnormal
      differentiation patterns in this model. Normal marrow transplants initially
      produce predominantly erythroid cells and later predominantly B-lymphoid cells in
      these mice, whereas most MDS samples produced predominantly granulopoietic cells.
      In 4 of 4 MDS cases, the regenerated cells showed the same clonal markers
      (trisomy 8, n = 3; and 5q-, n = 1) as the original sample and, in one instance,
      regenerated trisomy 8(+) B-lymphoid as well as myeloid cells were identified.
      Interestingly, the enhanced growth of normal marrow obtained in NOD/SCID-beta2m(
      /-) mice engineered to produce human interleukin-3, granulocyte-macrophage colony
      stimulating factor, and Steel factor was seen only with 1 of 7 MDS samples. These
      findings support the concept that human MDS originates in a transplantable
      multilineage hematopoietic stem cell whose genetic alteration may affect patterns
      of differentiation and responsiveness to hematopoietic growth factors. They also
      demonstrate the potential of this new murine xenotransplant model for future
      investigations of MDS.

PMID- 14962906
TI  - Effect of chronic cytokine therapy on clonal dynamics in nonhuman primates.
AB  - Hematopoietic cytokines such as filgrastim are used extensively to stimulate
      granulocyte production or to mobilize hematopoietic progenitors into the
      circulation; however, their effect on more primitive hematopoietic progenitor and
      stem cells in vivo is unknown, particularly in large animals or humans. In
      particular, there is concern that chronic therapy with cytokines could result in
      stem cell exhaustion or clonal dominance; however, direct assessment of the
      dynamics of individual stem and progenitor cell clones in vivo has not been
      previously reported. A number of models can be proposed regarding the mechanisms
      by which the marrow responds to cytokine stimulation, including recruitment of
      previously quiescent clones, stimulation of proliferation of already active
      clones, or prevention of apoptosis of more mature progenitors from all clones.
      Using retroviral marking and comprehensive insertion site tracking of individual
      stem and progenitor cell clones in 2 rhesus macaques, we analyzed the effect of
      chronic administration of granulocyte colony-stimulating factor (G-CSF), or a
      combination of G-CSF plus stem cell factor (SCF). The overall number of
      contributing clones remained constant, and the relative output from each clone
      did not change significantly during or following cytokine treatments. These
      results suggest that individual transduced stem or progenitor cells can
      contribute to hematopoiesis for prolonged periods, with no evidence for an effect
      of G-CSF or G-CSF/SCF on the number, the lifespan, or the relative activity of
      individual stem or progenitor cell clones. These relevant large animal studies
      are reassuring regarding clinical applications of cytokines and provide new
      insights into their mechanisms of action.

PMID- 14962907
TI  - Clinical management of thrombophilia-related placental vascular complications.
AB  - Pregnancy is a hypercoagulable state with an increased thrombotic risk throughout
      gestation and the postpartum period. Women with thrombophilia may have a further
      increased risk of placental vascular complications, including pregnancy loss,
      preeclampsia, intrauterine growth restriction, and placental abruption.
      Preliminary data suggest that maternal antithrombotic prophylaxis may result in
      improved gestational outcome. Randomized trials are under way and hopefully will
      optimize maternal and neonatal outcome.

PMID- 14962908
TI  - pDP4, a novel glycoprotein secreted by mature granulocytes, is regulated by
      transcription factor PU.1.
AB  - The transcription factor PU.1 (Spi-1) is a well-characterized regulator of
      myeloid and lymphoid development. However, its role in mature functional cells is
      poorly studied. Here we report the characterization of the novel murine gene pDP4
      (PU.1 difference product 4), which is absent from fetal livers of PU.1-deficient
      mice. pDP4 is transcribed as a single 3.2-kb mRNA with a 1518-base pair open
      reading frame encoded by 5 exons on chromosome 14. pDP4 expression is strongest
      in small intestine and bone marrow, in which it is expressed predominately in
      mature neutrophils. Interestingly, however, pDP4 expression is markedly down
      regulated in neutrophils of the peripheral blood and peritoneum. The pDP4 gene
      encodes a secreted 57-kDa glycoprotein with an olfactomedin-like C-terminus. PU.1
      binds to a functional site within the pDP4 promoter, and pDP4 expression in
      myeloid cells is strictly dependent on PU.1 and the presence of this site. In
      conclusion, we have identified a novel PU.1-regulated extracellular glycoprotein
      of the olfactomedin-like family with a possible role in neutrophilic trafficking.

PMID- 14962909
TI  - Mechanisms of early peripheral CD4 T-cell tolerance induction by anti-CD154
      monoclonal antibody and allogeneic bone marrow transplantation: evidence for
      anergy and deletion but not regulatory cells.
AB  - Anti-CD154 (CD40L) monoclonal antibody (mAb) plus bone marrow transplantation
      (BMT) in mice receiving CD8 cell-depleting mAb leads to long-term mixed
      hematopoietic chimerism and systemic donor-specific tolerance through peripheral
      and central deletional mechanisms. However, CD4(+) T-cell tolerance is
      demonstrable in vitro and in vivo rapidly following BMT, before deletion of donor
      reactive CD4 cells is complete, suggesting the involvement of other mechanisms.
      We examined these mechanisms in more detail. Spot enzyme-linked immunosorbent
      (ELISPOT) analysis revealed specific tolerization (within 4 to 15 days) of both T
      helper 1 (Th1) and Th2 cytokine responses to the donor, with no evidence for
      cytokine deviation. Tolerant lymphocytes did not significantly down-regulate
      rejection by naive donor-reactive T cells in adoptive transfer experiments. No
      evidence for linked suppression was obtained when skin expressing donor
      alloantigens in association with third-party alloantigens was grafted. T-cell
      receptor (TCR) transgenic mixing studies revealed that specific peripheral
      deletion of alloreactive CD4 T cells occurs over the first 4 weeks following BMT
      with anti-CD154. In contrast to models involving anti-CD154 without BMT, BMT with
      anti-CD154 leads to the rapid induction of anergy, followed by deletion of pre
      existing donor-reactive peripheral CD4(+) T cells; the rapid deletion of these
      cells obviates the need for a regulatory cell population to suppress CD4 cell
      mediated alloreactivity.

PMID- 14962910
TI  - The role of apoptosis in the development of AGM hematopoietic stem cells revealed
      by Bcl-2 overexpression.
AB  - Apoptosis is an essential process in embryonic tissue remodeling and adult tissue
      homeostasis. Within the adult hematopoietic system, it allows for tight
      regulation of hematopoietic cell subsets. Previously, it was shown that B-cell
      leukemia 2 (Bcl-2) overexpression in the adult increases the viability and
      activity of hematopoietic cells under normal and/or stressful conditions.
      However, a role for apoptosis in the embryonic hematopoietic system has not yet
      been established. Since the first hematopoietic stem cells (HSCs) are generated
      within the aortagonad-mesonephros (AGM; an actively remodeling tissue) region
      beginning at embryonic day 10.5, we examined this tissue for expression of
      apoptosis-related genes and ongoing apoptosis. Here, we show expression of
      several proapoptotic and antiapoptotic genes in the AGM. We also generated
      transgenic mice overexpressing Bcl-2 under the control of the transcriptional
      regulatory elements of the HSC marker stem cell antigen-1 (Sca-1), to test for
      the role of cell survival in the regulation of AGM HSCs. We provide evidence for
      increased numbers and viability of Sca-1(+) cells in the AGM and subdissected
      midgestation aortas, the site where HSCs are localized. Most important, our in
      vivo transplantation data show that Bcl-2 overexpression increases AGM and fetal
      liver HSC activity, strongly suggesting that apoptosis plays a role in HSC
      development.

PMID- 14962911
TI  - NPM-ALK fusion kinase of anaplastic large-cell lymphoma regulates survival and
      proliferative signaling through modulation of FOXO3a.
AB  - Between 30% and 50% of patients with advanced-stage anaplastic large-cell
      lymphoma (ALCL) harbor the balanced chromosomal rearrangement t(2;5)(p23;q35),
      which results in the generation of the fusion protein nucleophosmin-anaplastic
      lymphoma kinase (NPM-ALK). To further study survival signaling by NPMALK, we
      generated Ba/F3 cell lines with either inducible or constitutive expression of
      NPM-ALK and examined the regulation of the AKT target FOXO3a. We hypothesized
      that NPM-ALK signaling through phosphoinositol 3-kinase (PI 3-kinase) and AKT
      would regulate FOXO3a, a member of the forkhead family of transcription factors,
      thereby stimulating proliferation and blocking programmed cell death in NPM-ALK
      transformed cells. In Ba/F3 cells with induced or constitutive expression of NPM
      ALK, concomitant AKT activation and phosphorylation of its substrate, FOXO3a, was
      observed. In addition, transient expression of NPM-ALK in U-20S cells inhibited
      FOXO3a-mediated transactivation of reporter gene expression. Furthermore, NPM-ALK
      induced FOXO3a phosphorylation in Ba/F3 cells resulted in nuclear exclusion of
      this transcriptional regulator, up-regulation of cyclin D2 expression, and down
      regulation of p27(kip1) and Bim-1 expression. NPMALK reversal of proliferation
      arrest and of p27(kip1) induction was dependent on the phosphorylation of FOXO3a.
      Thus, FOXO3a is a barrier to hematopoietic transformation that is overcome by
      phosphorylation and cytoplasmic relocalization induced by the expression of NPM
      ALK.

PMID- 14962912
TI  - Improved prediction of MHC class I and class II epitopes using a novel Gibbs
      sampling approach.
AB  - MOTIVATION: Prediction of which peptides will bind a specific major
      histocompatibility complex (MHC) constitutes an important step in identifying
      potential T-cell epitopes suitable as vaccine candidates. MHC class II binding
      peptides have a broad length distribution complicating such predictions. Thus,
      identifying the correct alignment is a crucial part of identifying the core of an
      MHC class II binding motif. In this context, we wish to describe a novel Gibbs
      motif sampler method ideally suited for recognizing such weak sequence motifs.
      The method is based on the Gibbs sampling method, and it incorporates novel
      features optimized for the task of recognizing the binding motif of MHC classes I
      and II. The method locates the binding motif in a set of sequences and
      characterizes the motif in terms of a weight-matrix. Subsequently, the weight
      matrix can be applied to identifying effectively potential MHC binding peptides
      and to guiding the process of rational vaccine design. RESULTS: We apply the
      motif sampler method to the complex problem of MHC class II binding. The input to
      the method is amino acid peptide sequences extracted from the public databases of
      SYFPEITHI and MHCPEP and known to bind to the MHC class II complex HLA
      DR4(B1*0401). Prior identification of information-rich (anchor) positions in the
      binding motif is shown to improve the predictive performance of the Gibbs
      sampler. Similarly, a consensus solution obtained from an ensemble average over
      suboptimal solutions is shown to outperform the use of a single optimal solution.
      In a large-scale benchmark calculation, the performance is quantified using
      relative operating characteristics curve (ROC) plots and we make a detailed
      comparison of the performance with that of both the TEPITOPE method and a weight
      matrix derived using the conventional alignment algorithm of ClustalW. The
      calculation demonstrates that the predictive performance of the Gibbs sampler is
      higher than that of ClustalW and in most cases also higher than that of the
      TEPITOPE method.

PMID- 14962913
TI  - Simple sequence repeat marker loci discovery using SSR primer.
AB  - SUMMARY: Simple sequence repeats (SSRs) have become important molecular markers
      for a broad range of applications, such as genome mapping and characterization,
      phenotype mapping, marker assisted selection of crop plants and a range of
      molecular ecology and diversity studies. With the increase in the availability of
      DNA sequence information, an automated process to identify and design PCR primers
      for amplification of SSR loci would be a useful tool in plant breeding programs.
      We report an application that integrates SPUTNIK, an SSR repeat finder, with
      Primer3, a PCR primer design program, into one pipeline tool, SSR Primer. On
      submission of multiple FASTA formatted sequences, the script screens each
      sequence for SSRs using SPUTNIK. The results are parsed to Primer3 for locus
      specific primer design. The script makes use of a Web-based interface, enabling
      remote use. AVAILABILITY: This program has been written in PERL and is freely
      available for non-commercial users by request from the authors. The Web-based
      version may be accessed at http://hornbill.cspp.latrobe.edu.au/

PMID- 14962914
TI  - Align-m--a new algorithm for multiple alignment of highly divergent sequences.
AB  - MOTIVATION: Multiple alignment of highly divergent sequences is a challenging
      problem for which available programs tend to show poor performance. Generally,
      this is due to a scoring function that does not describe biological reality
      accurately enough or a heuristic that cannot explore solution space efficiently
      enough. In this respect, we present a new program, Align-m, that uses a non
      progressive local approach to guide a global alignment. RESULTS: Two large test
      sets were used that represent the entire SCOP classification and cover sequence
      similarities between 0 and 50% identity. Performance was compared with the
      publicly available algorithms ClustalW, T-Coffee and DiAlign. In general, Align-m
      has comparable or slightly higher accuracy in terms of correctly aligned
      residues, especially for distantly related sequences. Importantly, it aligns much
      fewer residues incorrectly, with average differences of over 15% compared with
      some of the other algorithms. AVAILABILITY: Align-m and the test sets are
      available at http://bioinformatics.vub.ac.be

PMID- 14962915
TI  - VARAN: a web server for variability analysis of DNA microarray experiments.
AB  - Here, we describe a tool for VARiability Analysis of DNA microarrays experiments
      (VARAN), a freely available Web server that performs a signal intensity based
      analysis of the log2 expression ratio variability deduced from DNA microarray
      data (one or two channels). Two modules are proposed: VARAN generator to compute
      a sliding windows analysis of the experimental variability (mean and SD) and
      VARAN analyzer to compare experimental data with an asymptotic variability model
      previously built with the generator module from control experiments. Both modules
      provide normalized intensity signals with five possible methods, log ratio values
      and a list of genes showing significant variations between conditions.
      AVAILABILITY: http://www.bionet.espci.fr/varan/ SUPPLEMENTARY INFORMATION:
      http://www.bionet.espci.fr/varan/help.html

PMID- 14962916
TI  - Analysis of variance components in gene expression data.
AB  - MOTIVATION: A microarray experiment is a multi-step process, and each step is a
      potential source of variation. There are two major sources of variation:
      biological variation and technical variation. This study presents a variance
      components approach to investigating animal-to-animal, between-array, within
      array and day-to-day variations for two data sets. The first data set involved
      estimation of technical variances for pooled control and pooled treated RNA
      samples. The variance components included between-array, and two nested within
      array variances: between-section (the upper- and lower-sections of the array are
      replicates) and within-section (two adjacent spots of the same gene are printed
      within each section). The second experiment was conducted on four different
      weeks. Each week there were reference and test samples with a dye-flip replicate
      in two hybridization days. The variance components included week-to-week, animal
      to-animal and between-array and within-array variances. RESULTS: We applied the
      linear mixed-effects model to quantify different sources of variation. In the
      first data set, we found that the between-array variance is greater than the
      between-section variance, which, in turn, is greater than the within-section
      variance. In the second data set, for the reference samples, the week-to-week
      variance is larger than the between-array variance, which, in turn, is slightly
      larger than the within-array variance. For the test samples, the week-to-week
      variance has the largest variation. The animal-to-animal variance is slightly
      larger than the between-array and within-array variances. However, in a gene-by
      gene analysis, the animal-to-animal variance is smaller than the between-array
      variance in four out of five housekeeping genes. In summary, the largest
      variation observed is the week-to-week effect. Another important source of
      variability is the animal-to-animal variation. Finally, we describe the use of
      variance-component estimates to determine optimal numbers of animals, arrays per
      animal and sections per array in planning microarray experiments.

PMID- 14962917
TI  - Gap statistics for whole genome shotgun DNA sequencing projects.
AB  - MOTIVATION: Investigators utilize gap estimates for DNA sequencing projects.
      Standard theories assume sequences are independently and identically distributed,
      leading to appreciable under-prediction of gaps. RESULTS: Using a statistical
      scaling factor and data from 20 representative whole genome shotgun projects, we
      construct regression equations that relate coverage to a normalized gap measure.
      Prokaryotic genomes do not correlate to sequence coverage, while eukaryotes show
      strong correlation if the chaff is ignored. Gaps decrease at an exponential rate
      of only about one-third of that predicted via theory alone. Case studies suggest
      that departure from theory can largely be attributed to assembly difficulties for
      repeat-rich genomes, but bias and coverage anomalies are also important when
      repeats are sparse. Such factors cannot be readily characterized a priori,
      suggesting upper limits on the accuracy of gap prediction. We also find that
      diminishing coverage probability discussed in other studies is a theoretical
      artifact that does not arise for the typical project.

PMID- 14962918
TI  - Amplicon: software for designing PCR primers on aligned DNA sequences.
AB  - SUMMARY: Amplicon is a program for designing PCR primers on aligned groups of DNA
      sequences. The most important application for Amplicon is the design of 'group
      specific' PCR primer sets that amplify a DNA region from a given taxonomic group
      but do not amplify orthologous regions from other taxonomic groups. AVAILABILITY:
      Amplicon is freely available as a script that will run on any platform with
      Python 2.3 installed (http://www.python.org). It is also available as a Windows
      executable. Free downloads that do not require registration can be found at
      http://www.aad.gov.au/amplicon

PMID- 14962919
TI  - OBIYagns: a grid-based biochemical simulator with a parameter estimator.
AB  - OBIYagns (yet another gene network simulator) is a biochemical system simulator
      that comprises a multiple-user Web-based graphical interface, an ordinary
      differential equation solver and a parameter estimators distributed over an open
      bioinformatics grid (OBIGrid). This grid-based biochemical simulation system can
      achieve high performance and provide a secure simulation environment for
      estimating kinetic parameters in an acceptable time period. OBIYagns can be
      applied to larger system biology-oriented simulation projects. AVAILABILITY:
      OBIYagns example models, methods and user guide are available at
      https://access.obigrid.org/yagns/ SUPPLEMENTARY INFORMATION: Please refer to
      Bioinformatics online.

PMID- 14962920
TI  - Evaluation and optimization of clustering in gene expression data analysis.
AB  - MOTIVATION: A measurement of cluster quality is needed to choose potential
      clusters of genes that contain biologically relevant patterns of gene expression.
      This is strongly desirable when a large number of gene expression profiles have
      to be analyzed and proper clusters of genes need to be identified for further
      analysis, such as the search for meaningful patterns, identification of gene
      functions or gene response analysis. RESULTS: We propose a new cluster quality
      method, called stability, by which unsupervised learning of gene expression data
      can be performed efficiently. The method takes into account a cluster's stability
      on partition. We evaluate this method and demonstrate its performance using four
      independent, real gene expression and three simulated datasets. We demonstrate
      that our method outperforms other techniques listed in the literature. The method
      has applications in evaluating clustering validity as well as identifying stable
      clusters. AVAILABILITY: Please contact the first author.

PMID- 14962921
TI  - A general computational model of mitochondrial metabolism in a whole organelle
      scale.
AB  - A computational tool for mitochondrial systems biology has been developed as a
      simulation model of E-Cell2, a publicly available simulation system. The general
      model consists of 58 enzymatic reactions and 117 metabolites, representing the
      respiratory chain, the TCA cycle, the fatty acid beta-oxidation and the inner
      membrane transport system. It is based on previously published enzyme kinetics
      studies in the literature; we have successfully integrated and packaged them into
      a single large model. The model can be easily extended and modified so that
      mitochondrial biologists/physiologists can integrate their own models and
      evaluate them in the context of the whole organelle metabolism. AVAILABILITY: The
      mitochondrial model is bundled up with E-Cell2 simulation system, which can be
      downloaded from http://www.e-cell.org. CD-ROMs are also available and are
      distributed at major conferences. SUPPLEMENTARY INFORMATION: All the kinetic data
      are available via http://www.e-cell.org

PMID- 14962922
TI  - Combining partial order alignment and progressive multiple sequence alignment
      increases alignment speed and scalability to very large alignment problems.
AB  - MOTIVATION: Partial order alignment (POA) has been proposed as a new approach to
      multiple sequence alignment (MSA), which can be combined with existing methods
      such as progressive alignment. This is important for addressing problems both in
      the original version of POA (such as order sensitivity) and in standard
      progressive alignment programs (such as information loss in complex alignments,
      especially surrounding gap regions). RESULTS: We have developed a new Partial
      Order-Partial Order alignment algorithm that optimally aligns a pair of MSAs and
      which therefore can be applied directly to progressive alignment methods such as
      CLUSTAL. Using this algorithm, we show the combined Progressive POA alignment
      method yields results comparable with the best available MSA programs (CLUSTALW,
      DIALIGN2, T-COFFEE) but is far faster. For example, depending on the level of
      sequence similarity, aligning 1000 sequences, each 500 amino acids long, took 15
      min (at 90% average identity) to 44 min (at 30% identity) on a standard PC. For
      large alignments, Progressive POA was 10-30 times faster than the fastest of the
      three previous methods (CLUSTALW). These data suggest that POA-based methods can
      scale to much larger alignment problems than possible for previous methods.
      AVAILABILITY: The POA source code is available at
      http://www.bioinformatics.ucla.edu/poa

PMID- 14962923
TI  - BioOptimizer: a Bayesian scoring function approach to motif discovery.
AB  - MOTIVATION: Transcription factors (TFs) bind directly to short segments on the
      genome, often within hundreds to thousands of base pairs upstream of gene
      transcription start sites, to regulate gene expression. The experimental
      determination of TFs binding sites is expensive and time-consuming. Many motif
      finding programs have been developed, but no program is clearly superior in all
      situations. Practitioners often find it difficult to judge which of the motifs
      predicted by these algorithms are more likely to be biologically relevant.
      RESULTS: We derive a comprehensive scoring function based on a full Bayesian
      model that can handle unknown site abundance, unknown motif width and two-block
      motifs with variable-length gaps. An algorithm called BioOptimizer is proposed to
      optimize this scoring function so as to reduce noise in the motif signal found by
      any motif-finding program. The accuracy of BioOptimizer, which can be used in
      conjunction with several existing programs, is shown to be superior to using any
      of these motif-finding programs alone when evaluated by both simulation studies
      and application to sets of co-regulated genes in bacteria. In addition, this
      scoring function formulation enables us to compare objectively different
      predicted motifs and select the optimal ones, effectively combining the strengths
      of existing programs. AVAILABILITY: BioOptimizer is available for download at
      www.fas.harvard.edu/~junliu/BioOptimizer/

PMID- 14962924
TI  - A perturbation-based method for calculating explicit likelihood of evolutionary
      co-variance in multiple sequence alignments.
AB  - MOTIVATION: The constituent amino acids of a protein work together to define its
      structure and to facilitate its function. Their interdependence should be
      apparent in the evolutionary record of each protein family: positions in the
      sequence of a protein family that are intimately associated in space or in
      function should co-vary in evolution. A recent approach by Ranganathan and
      colleagues proposes to look at subsets of a protein family, selected for their
      sequence at one position, to see how this affects variation at other positions.
      RESULTS: We present a quantitative algorithm for assessing covariation with this
      approach, based on explicit likelihood calculations. By applying our algorithm to
      138 Pfam families with at least one member of known structure, we demonstrate
      that our method has improved power in finding physically close residues in
      crystal structures, compared to that of Ranganathan and colleagues. SUPPLEMENTARY
      INFORMATION: www.afodor.net/bioinfosup.html

PMID- 14962925
TI  - Evaluating the predictability of conformational switching in RNA.
AB  - MOTIVATION: There are various cases where the biological function of an RNA
      molecule involves a reversible change of conformation. paRNAss is a software
      approach to the prediction of such structural switching in RNA. It is based on
      three hypotheses about the secondary structure space of a switching RNA molecule
      that can be evaluated by RNA folding and structure comparison. In the positive
      case, the predicted structural switching must be verified experimentally.
      RESULTS: After reviewing the strategy used in paRNAss, we present recent
      improvements on the algorithmic level of the approach, and the results of an
      evaluation procedure, comprising 1500 RNA sequences. It could be shown that the
      paRNAss approach performs well on known examples for conformational switching in
      RNA. The overall number of positive predictions was small, whereas for human 3'
      UTRs, representing regulatory important regions, it was substantially higher than
      for arbitrary natural and random sequences. AVAILABILITY: paRNAss is available as
      a Web service at http://bibiserv.techfak.uni-bielefeld.de/parnass SUPPLEMENTARY
      INFORMATION: Detailed information on the analyses summarized in Table 1 can be
      found at http://bibiserv.techfak.uni-bielefeld.de/parnass/examples.html

PMID- 14962926
TI  - A graph theoretical approach for predicting common RNA secondary structure motifs
      including pseudoknots in unaligned sequences.
AB  - MOTIVATION: RNA structure motifs contained in mRNAs have been found to play
      important roles in regulating gene expression. However, identification of novel
      RNA regulatory motifs using computational methods has not been widely explored.
      Effective tools for predicting novel RNA regulatory motifs based on genomic
      sequences are needed. RESULTS: We present a new method for predicting common RNA
      secondary structure motifs in a set of functionally or evolutionarily related RNA
      sequences. This method is based on comparison of stems (palindromic helices)
      between sequences and is implemented by applying graph-theoretical approaches. It
      first finds all possible stable stems in each sequence and compares stems
      pairwise between sequences by some defined features to find stems conserved
      across any two sequences. Then by applying a maximum clique finding algorithm, it
      finds all significant stems conserved across at least k sequences. Finally, it
      assembles in topological order all possible compatible conserved stems shared by
      at least k sequences and reports a number of the best assembled stem sets as the
      best candidate common structure motifs. This method does not require prior
      structural alignment of the sequences and is able to detect pseudoknot
      structures. We have tested this approach on some RNA sequences with known
      secondary structures, in which it is capable of detecting the real structures
      completely or partially correctly and outperforms other existing programs for
      similar purposes. AVAILABILITY: The algorithm has been implemented in C++ in a
      program called comRNA, which is available at http://ural.wustl.edu/softwares.html

PMID- 14962927
TI  - Analysis of disturbed images.
AB  - MOTIVATION: Images in cellular and molecular biology (from microscopy, blots,
      biochips, etc.) are often disturbed, so that the detection and analysis of the
      respective relevant geometrical objects may be difficult or error-prone. The
      disturbances are either caused by the detector, usually a CCD camera, or by the
      experimental setup. Furthermore, microtechnology experiments often require
      simultaneous multiple-colour stainings. Therefore, the image analysis of such
      experiments should be colour-sensitive, and colour shadings should not only be
      detectable but also quantifiable. RESULTS: Here, we describe a general solution
      as applied to the analysis of blots and DNA chips as well as to microscopy images
      of tissues. We decided to use (i) a stochastic filter as used by Wiener for image
      segmentation as the starting point for object detection, (ii) chaincodes as
      described by Freeman for object description, (iii) a novel 'rolling disc
      algorithm' to spot the objects to be analysed and (iv) an HSI instead of an RGB
      colour model for colour analysis. With this combination we succeeded in
      performing shape detection and colour-based analysis of disturbed images.
      AVAILABILITY: The corresponding modules (C++) are available on request.

PMID- 14962928
TI  - Rapid 3D protein structure database searching using information retrieval
      techniques.
AB  - MOTIVATION: As the sizes of three-dimensional (3D) protein structure databases
      are growing rapidly nowadays, exhaustive database searching, in which a 3D query
      structure is compared to each and every structure in the database, becomes
      inefficient. We propose a rapid 3D protein structure retrieval system named
      'ProtDex2', in which we adopt the techniques used in information retrieval
      systems in order to perform rapid database searching without having access to
      every 3D structure in the database. The retrieval process is based on the
      inverted-file index constructed on the feature vectors of the relationships
      between the secondary structure elements (SSEs) of all the 3D protein structures
      in the database. ProtDex2 is a significant improvement, both in terms of speed
      and accuracy, upon its predecessor system, ProtDex. RESULTS: The experimental
      results show that ProtDex2 is very much faster than two well-known protein
      structure comparison methods, DALI and CE, yet not sacrificing on the accuracy of
      the comparison. When comparing with a similar SSE-based method, namely TopScan,
      ProtDex2 is much faster with comparable degree of accuracy. AVAILABILITY: The
      software is available at: http://xena1.ddns.comp.nus.edu.sg/~genesis/PD2.htm

PMID- 14962929
TI  - GeneAnnot: comprehensive two-way linking between oligonucleotide array probesets
      and GeneCards genes.
AB  - MOTIVATION: High density oligonucleotide arrays are usually annotated in a one-to
      one fashion, with each probeset assigned to one gene. However, in reality,
      subsets of oligonucleotides in a probeset may match sequences within more than
      one gene, potentially leading to misinterpretations. Moreover, a gene is often
      represented by more than one probeset, and analyzing probe matches at the mRNA
      level can help one deduce whether these probesets are derived from the same or
      different splice variants. RESULTS: The GeneAnnot system comprehensively
      documents the many-to-many relationship between oligonucleotide array probesets
      and annotated genes in GeneCards. It performs pairwise alignments between the
      probe sequences and gene transcripts, and assigns sensitivity and specificity
      scores to each probeset/gene pair. AVAILABILITY:
      http://genecards.weizmann.ac.il/geneannot/ SUPPLEMENTARY INFORMATION: Program
      description and statistics
      http://genecards.weizmann.ac.il/geneannot/DOC/index.html

PMID- 14962930
TI  - ParSeq: searching motifs with structural and biochemical properties.
AB  - SUMMARY: Searches for variable motifs such as protein-binding sites or promoter
      regions are more complex than the search for casual motifs. For example, in amino
      acid sequences comparing motifs alone mostly proves to be insufficient to detect
      regions that represent proteins with a special function, because the function
      depends on biochemical properties of individual amino acids (such as polarity or
      hydrophobicity). Pure string matching programs are not able to find these motifs;
      hence, we developed ParSeq, a program that combines the search for motifs with
      certain structural properties, the verification of biochemical properties, an
      approximate search mechanism and a stepwise creation of the motif description by
      allowing to search on previously obtained results. AVAILABILITY: http://www
      pr.informatik.uni-tuebingen.de/parseq

PMID- 14962931
TI  - RAG: RNA-As-Graphs database--concepts, analysis, and features.
AB  - MOTIVATION: Understanding RNA's structural diversity is vital for identifying
      novel RNA structures and pursuing RNA genomics initiatives. By classifying RNA
      secondary motifs based on correlations between conserved RNA secondary structures
      and functional properties, we offer an avenue for predicting novel motifs.
      Although several RNA databases exist, no comprehensive schemes are available for
      cataloguing the range and diversity of RNA's structural repertoire. RESULTS: Our
      RNA-As-Graphs (RAG) database describes and ranks all mathematically possible
      (including existing and candidate) RNA secondary motifs on the basis of graphical
      enumeration techniques. We represent RNA secondary structures as two-dimensional
      graphs (networks), specifying the connectivity between RNA secondary structural
      elements, such as loops, bulges, stems and junctions. We archive RNA tree motifs
      as 'tree graphs' and other RNAs, including pseudoknots, as general 'dual graphs'.
      All RNA motifs are catalogued by graph vertex number (a measure of sequence
      length) and ranked by topological complexity. The RAG inventory immediately
      suggests candidates for novel RNA motifs, either naturally occurring or
      synthetic, and thereby might stimulate the prediction and design of novel RNA
      motifs. AVAILABILITY: The database is accessible on the web at
      http://monod.biomath.nyu.edu/rna

PMID- 14962932
TI  - Automatic prediction of protein domains from sequence information using a hybrid
      learning system.
AB  - MOTIVATION: We describe a novel method for detecting the domain structure of a
      protein from sequence information alone. The method is based on analyzing
      multiple sequence alignments that are derived from a database search. Multiple
      measures are defined to quantify the domain information content of each position
      along the sequence and are combined into a single predictor using a neural
      network. The output is further smoothed and post-processed using a probabilistic
      model to predict the most likely transition positions between domains. RESULTS:
      The method was assessed using the domain definitions in SCOP and CATH for
      proteins of known structure and was compared with several other existing methods.
      Our method performs well both in terms of accuracy and sensitivity. It improves
      significantly over the best methods available, even some of the semi-manual ones,
      while being fully automatic. Our method can also be used to suggest and verify
      domain partitions based on structural data. A few examples of predicted domain
      definitions and alternative partitions, as suggested by our method, are also
      discussed. AVAILABILITY: An online domain-prediction server is available at
      http://biozon.org/tools/domains/

PMID- 14962933
TI  - NetAffx Gene Ontology Mining Tool: a visual approach for microarray data
      analysis.
AB  - SUMMARY: The NetAffx Gene Ontology (GO) Mining Tool is a web-based, interactive
      tool that permits traversal of the GO graph in the context of microarray data. It
      accepts a list of Affymetrix probe sets and renders a GO graph as a heat map
      colored according to significance measurements. The rendered graph is
      interactive, with nodes linked to public web sites and to lists of the relevant
      probe sets. The GO Mining Tool provides visualization combining biological
      annotation with expression data, encompassing thousands of genes in one
      interactive view. AVAILABILITY: GO Mining Tool is freely available at
      http://www.affymetrix.com/analysis/query/go_analysis.affx

PMID- 14962934
TI  - GOstat: find statistically overrepresented Gene Ontologies within a group of
      genes.
AB  - SUMMARY: Modern experimental techniques, as for example DNA microarrays, as a
      result usually produce a long list of genes, which are potentially interesting in
      the analyzed process. In order to gain biological understanding from this type of
      data, it is necessary to analyze the functional annotations of all genes in this
      list. The Gene-Ontology (GO) database provides a useful tool to annotate and
      analyze the functions of a large number of genes. Here, we introduce a tool that
      utilizes this information to obtain an understanding of which annotations are
      typical for the analyzed list of genes. This program automatically obtains the GO
      annotations from a database and generates statistics of which annotations are
      overrepresented in the analyzed list of genes. This results in a list of GO terms
      sorted by their specificity. AVAILABILITY: Our program GOstat is accessible via
      the Internet at http://gostat.wehi.edu.au

PMID- 14962935
TI  - ACID: a database for microarray clone information.
AB  - SUMMARY: Array Close Information Database is an online database for information
      about microarray cDNA clones. For each clone, the database contents include
      assigned UniGene cluster(s), location in the full-length transcript, assigned
      gene ontology terms and position in the genome assembly. AVAILABILITY:
      http://bioinfo.thep.lu.se/acid.html

PMID- 14962936
TI  - A comparison of scoring functions for protein sequence profile alignment.
AB  - MOTIVATION: In recent years, several methods have been proposed for aligning two
      protein sequence profiles, with reported improvements in alignment accuracy and
      homolog discrimination versus sequence-sequence methods (e.g. BLAST) and profile
      sequence methods (e.g. PSI-BLAST). Profile-profile alignment is also the iterated
      step in progressive multiple sequence alignment algorithms such as CLUSTALW.
      However, little is known about the relative performance of different profile
      profile scoring functions. In this work, we evaluate the alignment accuracy of 23
      different profile-profile scoring functions by comparing alignments of 488 pairs
      of sequences with identity < or =30% against structural alignments. We optimize
      parameters for all scoring functions on the same training set and use profiles of
      alignments from both PSI-BLAST and SAM-T99. Structural alignments are constructed
      from a consensus between the FSSP database and CE structural aligner. We compare
      the results with sequence-sequence and sequence-profile methods, including BLAST
      and PSI-BLAST. RESULTS: We find that profile-profile alignment gives an average
      improvement over our test set of typically 2-3% over profile-sequence alignment
      and approximately 40% over sequence-sequence alignment. No statistically
      significant difference is seen in the relative performance of most of the scoring
      functions tested. Significantly better results are obtained with profiles
      constructed from SAM-T99 alignments than from PSI-BLAST alignments. AVAILABILITY:
      Source code, reference alignments and more detailed results are freely available
      at http://phylogenomics.berkeley.edu/profilealignment/

PMID- 14962937
TI  - COACH: profile-profile alignment of protein families using hidden Markov models.
AB  - MOTIVATION: Alignments of two multiple-sequence alignments, or statistical models
      of such alignments (profiles), have important applications in computational
      biology. The increased amount of information in a profile versus a single
      sequence can lead to more accurate alignments and more sensitive homolog
      detection in database searches. Several profile-profile alignment methods have
      been proposed and have been shown to improve sensitivity and alignment quality
      compared with sequence-sequence methods (such as BLAST) and profile-sequence
      methods (e.g. PSI-BLAST). Here we present a new approach to profile-profile
      alignment we call Comparison of Alignments by Constructing Hidden Markov Models
      (HMMs) (COACH). COACH aligns two multiple sequence alignments by constructing a
      profile HMM from one alignment and aligning the other to that HMM. RESULTS: We
      compare the alignment accuracy of COACH with two recently published methods: Yona
      and Levitt's prof_sim and Sadreyev and Grishin's COMPASS. On two sets of
      reference alignments selected from the FSSP database, we find that COACH is able,
      on average, to produce alignments giving the best coverage or the fewest errors,
      depending on the chosen parameter settings. AVAILABILITY: COACH is freely
      available from www.drive5.com/lobster

PMID- 14962938
TI  - Modeling T-cell activation using gene expression profiling and state-space
      models.
AB  - MOTIVATION: We have used state-space models to reverse engineer transcriptional
      networks from highly replicated gene expression profiling time series data
      obtained from a well-established model of T-cell activation. State space models
      are a class of dynamic Bayesian networks that assume that the observed
      measurements depend on some hidden state variables that evolve according to
      Markovian dynamics. These hidden variables can capture effects that cannot be
      measured in a gene expression profiling experiment, e.g. genes that have not been
      included in the microarray, levels of regulatory proteins, the effects of
      messenger RNA and protein degradation, etc. RESULTS: Bootstrap confidence
      intervals are developed for parameters representing 'gene-gene' interactions over
      time. Our models represent the dynamics of T-cell activation and provide a
      methodology for the development of rational and experimentally testable
      hypotheses. AVAILABILITY: Supplementary data and Matlab computer source code will
      be made available on the web at the URL given below. SUPPLEMENTARY INFORMATION:
      http://public.kgi.edu/~wild/LDS/index.htm

PMID- 14962939
TI  - Site2genome: locating short DNA sequences in whole genomes.
AB  - SUMMARY: Many biological papers describe short, functional DNA sites without
      specifying their exact positions in the genome. We have developed a Web server
      that automates the tedious task of locating such sites in eukaryotic genomes,
      thus giving access to the context of rich annotations that are increasingly
      available for genome sequences. AVAILABILITY: http://zlab.bu.edu/site2genome/

PMID- 14962940
TI  - A hint to search for metalloproteins in gene banks.
AB  - MOTIVATION: With the advent of genome sequencing, a huge database of protein
      primary sequences has been accumulating. In parallel, a number of tools to
      investigate and expand upon this information, e.g. reconstructing and building
      relationships between protein families and superfamilies, have been developed.
      Metalloproteins are proteins capable of binding one or more metal ions, which are
      required for their biological function or for regulation of their activities or
      for structural purposes. Sometimes, metal binding can be observed in vitro but
      not be physiologically relevant. At present, there is a lack of specific tools to
      address the matter of the identification of metalloproteins in databases of gene
      sequences. RESULTS: In the present work, an approach exploiting metal-binding
      patterns (MBPs) of metalloproteins present in the Protein Data Bank to search
      gene banks for new metalloproteins is presented and applied to copper proteins.
      Nearly 100 different MBPs have been identified and then used for subsequent
      applications. The ensemble of sequences of the whole PDB is used to assess the
      potentiality and limits of the method and to identify levels of confidence for
      the predictions output by the search. It appears that copper-binding capabilities
      are identified with a confidence >90% when the percentage of identical amino
      acids aligned around the MBP by PHI-BLAST is at least 20% with respect to the
      entire protein domain length. If this percentage is between 10% and 20%, the
      level of confidence is approximately 50%. Application of the methodology to the
      entire genome sequences of Pyrococcus furiosus, Escherichia coli, Drosophila
      melanogaster and Homo sapiens suggests some differentiation between prokaryotes
      and eukaryotes. SUPPLEMENTARY INFORMATION: A table reporting statistics on the
      MBP identified; a list of all hits retrieved for the four organisms considered; a
      figure showing the number of hits for the four organisms as a function of
      I(d)(Global).

PMID- 14962941
TI  - ToPNet--an application for interactive analysis of expression data and biological
      networks.
AB  - SUMMARY: ToPNet is a new tool for the combined visualization and exploration of
      gene networks and expression data. ToPNet provides various ways of restricting,
      manipulating and combining biological networks according to annotation data (e.g.
      Gene Ontology terms) and presents results to the user via different visualization
      procedures and hyperlinks to the underlying data sources. To easily identify
      relevant parts of the network, ToPNet provides a method of detecting significant
      subnetworks with respect to expression measurements. As ToPNet is a pure JAVA
      application with additional scripting capabilities, it is well-suited as a test
      bed for algorithm development and exploratory biological data analysis alike.
      AVAILABILITY: ToPNet is freely available for academic institutions at
      http://www.biosolveit.de/ToPNet/

PMID- 14962942
TI  - QDist--quartet distance between evolutionary trees.
AB  - SUMMARY: QDist is a program for computing the quartet distance between two
      unrooted trees, i.e. the number of quartet topology differences between the
      trees, where a quartet topology is the topological subtree induced by four
      species. The program is based on an algorithm with running time O(n log2 n),
      which makes it practical to compare large trees. Available under GNU license.
      AVAILABILITY: http://www.birc.dk/Software/QDist

PMID- 14962943
TI  - Application of the GA/KNN method to SELDI proteomics data.
AB  - SUMMARY: Proteomics technology has shown promise in identifying biomarkers for
      disease, toxicant exposure and stress. We show by example that the genetic
      algorithm/k-nearest neighbors method, developed for mining high-dimensional
      microarray gene expression data, is also capable of mining surface enhanced laser
      desorption/ionization-time-of-flight proteomics data. AVAILABILITY: The source
      code of the program and documentation on how to use it are freely available to
      non-commercial users at http://dir.niehs.nih.gov/dirbb/lifiles/softlic.htm

PMID- 14962944
TI  - Involvement of neuron-derived orphan receptor-1 (NOR-1) in LDL-induced mitogenic
      stimulus in vascular smooth muscle cells: role of CREB.
AB  - OBJECTIVE: Low density lipoproteins (LDLs) modulate the expression of key genes
      involved in atherogenesis. Recently, we have shown that the transcription factor
      neuron-derived orphan receptor-1 (NOR-1) is involved in vascular smooth muscle
      cell (VSMC) proliferation. Our aim was to analyze whether NOR-1 is involved in
      LDL-induced mitogenic effects in VSMC. METHODS AND RESULTS: LDL induced NOR-1
      expression in a time- and dose-dependent manner. Antisense oligonucleotides
      against NOR-1 inhibit DNA synthesis induced by LDL in VSMCs as efficiently as
      antisense against the protooncogene c-fos. The upregulation of NOR-1 mRNA levels
      by LDL involves pertusis-sensitive G protein-coupled receptors, Ca2+
      mobilization, protein kinases A (PKA) and C (PKC) activation, and mitogen
      activated protein kinase pathways (MAPK) (p44/p42 and p38). LDL promotes cAMP
      response element binding protein (CREB) activation (phosphorylation in Ser133).
      In transfection assays a dominant-negative of CREB inhibits NOR-1 promoter
      activity, while mutation of specific (cAMP response element) CRE sites in the NOR
      1 promoter abolishes LDL-induced NOR-1 promoter activity. CONCLUSIONS: In VSMCs,
      LDL-induced mitogenesis involves NOR-1 upregulation through a CREB-dependent
      mechanism. CREB could play a role in the modulation by LDL of key genes
      (containing CRE sites) involved in atherogenesis.

PMID- 14962945
TI  - Clinical and biochemical results of the metalloproteinase inhibition with
      subantimicrobial doses of doxycycline to prevent acute coronary syndromes (MIDAS)
      pilot trial.
AB  - BACKGROUND: Vulnerable plaque demonstrates intense inflammation in which
      macrophages secrete matrix metalloproteinases (MMPs) that degrade the fibrous
      cap, ultimately leading to rupture, in situ thrombosis, and an associated
      clinical event. Thus, inhibition of MMP activity or more general suppression of
      vascular inflammation are attractive targets for interventions intended to reduce
      plaque rupture. We hypothesized that subantimicrobial doses of doxycycline (SDD)
      (20 mg twice daily) would benefit patients with coronary artery disease by
      reducing inflammation and MMP activity and thus possibly prevent coronary plaque
      rupture events. METHODS AND RESULTS: We conducted a prospective, randomized,
      double-blind, placebo-controlled pilot study of 6 months of SDD or placebo
      treatment to reduce inflammation and prevent plaque rupture events. A total of 50
      patients were enrolled, of whom 24 were randomized to placebo and 26 to SDD. At 6
      months, there was no difference in the composite endpoint of sudden death, fatal
      myocardial infarction (MI), non-fatal MI, or troponin-positive unstable angina in
      SDD compared with placebo-treated patients (8.4% versus 0%, P=0.491). Biochemical
      markers of inflammation were assessed in plasma at study entry and after 6 months
      of therapy in 30 patients. In SDD-treated patients, high-sensitivity C-reactive
      protein (CRP) was reduced by 46% from 4.8+/-0.6 microg/mL to 2.6+/-0.4 microg/mL
      (P=0.007), whereas CRP was not significantly reduced in placebo patients.
      Interleukin (IL)-6 decreased from 22.1+/-3.7 pg/mL at baseline to 14.7+/-1.8
      pg/mL at 6 months in SDD-treated patients (P=0.025) but did not decrease
      significantly in placebo-treated patients. On zymography, pro-MMP-9 activity was
      reduced 50% by SDD therapy (P=0.011), whereas it was unchanged by placebo
      treatment. CONCLUSIONS: SDD appears to exert potentially beneficial effects on
      inflammation that could promote plaque stability. These findings should be
      investigated in a larger study.

PMID- 14962946
TI  - Cholesterol 7alpha-hydroxylase deficiency in mice on an APOE*3-Leiden background
      impairs very-low-density lipoprotein production.
AB  - OBJECTIVE: Cholesterol 7alpha-hydroxylase (cyp7a1) catalyzes the rate-limiting
      step in conversion of cholesterol to bile acids. To study the relationship
      between bile acid biosynthesis and triglyceride metabolism, we cross-bred mice
      lacking cyp7a1 on a hyperlipidemic APOE*3-Leiden background. METHODS AND RESULTS:
      Female mice received a chow or lipogenic diet. On both diets, fecal bile acid
      excretion was 70% decreased concomitantly with a 2-fold increased neutral sterol
      output. The differences in bile acid biosynthesis did not change plasma
      cholesterol levels. However, plasma triglyceride levels decreased by 41% and 38%
      in the cyp7a1-/-. APOE*3-Leiden mice as compared with APOE*3-Leiden mice on chow
      and lipogenic diet, respectively. Mechanistic studies showed that very-low
      density lipoprotein (VLDL)-apolipoprotein B and VLDL-triglyceride production
      rates were reduced in cyp7a1-/-. APOE*3-Leiden mice as compared with APOE*3
      Leiden mice (-34% and -35%, respectively). Cyp7a1 deficiency also increased the
      hepatic cholesteryl ester and triglyceride content (2.8-fold and 2.5-fold,
      respectively). In addition, hepatic anti-oxidative vitamin content, which can
      influence VLDL-production, was lower. Hepatic mRNA analysis showed decreased
      expression of genes involved in lipogenesis including srebf1. CONCLUSIONS: Cyp7a1
      deficiency in APOE*3-Leiden mice decreases the VLDL particle production rate, as
      a consequence of a strongly reduced bile acid biosynthesis, leading to a decrease
      in plasma triglycerides. These data underscore the close relationship between
      bile acid biosynthesis and triglyceride levels.

PMID- 14962947
TI  - In-depth haplotype analysis of ABCA1 gene polymorphisms in relation to plasma
      ApoA1 levels and myocardial infarction.
AB  - OBJECTIVE: By regulating the cellular cholesterol efflux from peripheral cells to
      high-density lipoprotein, the ABCA1 protein is suspected to play a key role in
      lipid homeostasis and atherosclerosis. Twenty-six polymorphisms of the ABCA1 gene
      were genotyped and tested for association with plasma levels of ApoA1 and
      myocardial infarction (MI) in the ECTIM study. METHODS AND RESULTS: In addition
      to single-locus analysis, a systematic exploration of all possible haplotype
      effects was performed, with this exploration being performed on a minimal set of
      "tag" polymorphisms that define the haplotype structure of the gene. Two
      polymorphisms were associated with plasma levels of ApoA1, 1 in the promoter (C
      564T) and 1 in the coding (R1587K) regions, whereas only 1 polymorphism (R219K)
      was associated with the risk of MI. However, no haplotype effect was detected on
      ApoA1 variability or on the risk of MI. CONCLUSIONS: ABCA1 gene polymorphisms but
      not haplotypes are involved in the variability of plasma ApoA1 and the
      susceptibility to coronary artery disease.

PMID- 14962948
TI  - Angiotensin II type 1a receptor is involved in cell infiltration, cytokine
      production, and neovascularization in infarcted myocardium.
AB  - OBJECTIVE: Angiotensin II is critically involved in left ventricular remodeling
      after myocardial infarction. Neovascularization has been thought to prevent the
      development of left ventricular remodeling and deterioration to heart failure. To
      elucidate the role of angiotensin II in neovascularization during cardiac
      remodeling, we induced myocardial infarction in angiotensin II type 1a receptor
      (AT1) knockout (KO) mice. METHODS AND RESULTS: There were more vessels in the
      border zone of infarcted hearts of wild-type (WT) mice and AT1KO mice at 14 days
      after operation, compared with in the left ventricle of sham-operated mice, and
      the number was larger in WT mice than in AT1KO mice. Consistent with these
      observations, the infarcted heart of AT1KO mice expressed lower levels of matrix
      metalloproteinase and endothelial nitric oxide synthase activity. More
      inflammatory cells such as granulocytes and macrophages were infiltrated in the
      infarcted hearts of WT mice than AT1KO mice at 4 days. A variety of cytokines and
      chemokines were increased in infarcted hearts of WT and AT1KO mice, and many of
      them were more remarkable in WT mice than in AT1KO mice at 14 days. CONCLUSIONS:
      AT1 plays a critical role in inflammatory cell infiltration, cytokine production,
      and neovascularization in infarcted hearts.

PMID- 14962949
TI  - Diabetic mouse angiopathy is linked to progressive sympathetic receptor deletion
      coupled to an enhanced caveolin-1 expression.
AB  - OBJECTIVE: Clinical studies have demonstrated that hyperglycaemia represents a
      major risk factor in the development of the endothelial impairment in diabetes,
      which is the first step in vascular dysfunction. Using non-obese diabetic mice,
      we have evaluated the role of the adrenergic system and eNOS on progression of
      the disease METHODS AND RESULTS: When glycosuria is high (20 to 500 mg/dL), there
      is a selective reduction in the response to alpha1 and beta2 agonists but not to
      dopamine or serotonin. When glycosuria is severe (500 to 1000 mg/dL), there is a
      complete ablation of the contracture response to the alpha1 receptor agonist
      stimulation and a marked reduced response to beta2 agonist stimulation. This
      effect is coupled with a reduced expression of alpha1 and beta2 receptors, which
      is caused by an inhibition at transcriptional level as demonstrated by RT-PCR. In
      the severe glycosuria (500 to 1000 mg/dL), although eNOS expression is unchanged,
      caveolin-1 expression is significantly enhanced, indicating that high glucose
      plasma levels cause an upregulation of the eNOS endogenous inhibitory tone. These
      latter results correlate with functional data showing that in severe glycosuria,
      there is a significant reduction in acetylcholine-induced vasodilatation.
      CONCLUSIONS: Our results show that in diabetes development, there is a
      progressive selective downregulation of the alpha1 and beta2 receptors. At the
      same time, there is an increased expression of caveolin-1, the endogenous eNOS
      inhibitory protein. Thus, caveolin-1 could represent a new possible therapeutic
      target in vascular impairment associated with diabetes.

PMID- 14962950
TI  - Group V sPLA2 hydrolysis of low-density lipoprotein results in spontaneous
      particle aggregation and promotes macrophage foam cell formation.
AB  - OBJECTIVE: Secretory phospholipase A2 (sPLA2) enzymes hydrolyze the sn-2 fatty
      acyl ester bond of phospholipids to produce a free fatty acid and a
      lysophospholid. Group V sPLA2 is expressed in cultured macrophage cells and has
      high affinity for phosphatidyl choline-containing substrates. The present study
      assesses the presence of group V sPLA2 in human and mouse atherosclerotic lesions
      and its activity toward low-density lipoprotein (LDL) particles. METHODS AND
      RESULTS: Group V sPLA2 was detected in human and mouse atherosclerotic lesions by
      immunohistochemical staining. Electron microscopic analysis showed that mouse
      group V sPLA2-modified LDL is significantly smaller (mean diameter+/-SEM=25.3+/
      0.25 nm) than native LDL (mean diameter+/-SEM=27.7+/-0.29 nm). Hydrolysis by
      group V sPLA2 induced spontaneous particle aggregation; the extent of aggregation
      was directly proportional to the degree of LDL hydrolysis. Group V sPLA2
      modification of LDL led to enhanced lipid accumulation in cultured mouse
      peritoneal macrophage cells. CONCLUSIONS: Group V sPLA2 may play an important
      role in promoting atherosclerotic lesion development by modifying LDL particles
      in the arterial wall, thereby enhancing particle aggregation, retention, and
      macrophage uptake.

PMID- 14962951
TI  - Patients with rheumatoid arthritis in clinical care.

PMID- 14962953
TI  - Validity, reliability, and applicability of seven definitions of hip
      osteoarthritis used in epidemiological studies: a systematic appraisal.
AB  - OBJECTIVE: To summarise and review articles addressing the quality (validity,
      reliability, applicability) of seven commonly used definitions of hip
      osteoarthritis (OA) for epidemiological studies in order to use it primarily as a
      classification criterion. METHODS: Medline and Embase were searched and articles
      studying the validity, reliability, or applicability of the definitions of hip OA
      were selected. Two reviewers independently extracted data on the quality of the
      seven definitions. RESULTS: Review of the literature showed the validity of the
      various definitions of hip OA, in particular, has barely been investigated.
      Minimal joint space (MJS) demonstrated the highest (intra- and interrater)
      reliability, and showed the highest association with hip pain and restricted
      internal rotation compared with the other definitions of hip OA. The reliability
      of the Kellgren and Lawrence grade and the index according to Lane is comparable
      with that of the MJS, but the construct validity should be investigated more
      thoroughly. The reliability and validity according to the Croft grade were
      inferior to the MJS, the Kellgren and Lawrence grade, and the index according to
      Lane. Despite precise and extensive development, the ACR criteria showed poor
      reliability and poor cross-validity (agreement between three ACR criteria sets)
      in a primary care setting. CONCLUSIONS: The reliabilities of MJS, Kellgren and
      Lawrence, and the index according to Lane were comparable, but the MJS had the
      highest relationship with hip pain in a male population. Considering how often
      definitions of hip OA are used, it is surprising that the validity has been so
      poorly investigated, and the validity needs to be studied more thoroughly.

PMID- 14962954
TI  - Case number 29: hitting three with one strike: rapid improvement of psoriatic
      arthritis, psoriatic erythroderma, and secondary renal amyloidosis by treatment
      with infliximab (Remicade).

PMID- 14962955
TI  - Activation of the STAT1 pathway in rheumatoid arthritis.
AB  - BACKGROUND: Expression of signal transducer and activator of transcription 1
      (STAT1), the mediator of interferon (IFN) signalling, is raised in synovial
      tissue (ST) from patients with rheumatoid arthritis (RA). OBJECTIVES: To
      determine the extent to which this pathway is activated by phosphorylation in RA
      synovium. Additionally, to investigate the cellular basis of STAT1 activation in
      RA ST. METHODS: ST specimens from 12 patients with RA and 14 disease controls
      (patients with osteoarthritis and reactive arthritis) were analysed by
      immunohistochemistry, using antibodies to STAT1, tyrosine phosphorylated STAT1,
      and serine phosphorylated STAT1. Lysates of cultured fibroblast-like synoviocytes
      stimulated with IFNbeta were analysed by western blotting. Phenotypic
      characterisation of cells expressing STAT1 in RA ST was performed by double
      immunolabelling for STAT1 and CD3, CD22, CD55, or CD68. RESULTS: Raised levels of
      total STAT1 protein and both its activated tyrosine and serine phosphorylated
      forms were seen in RA synovium as compared with controls. STAT1 was predominantly
      abundant in T and B lymphocytes in focal inflammatory infiltrates and in
      fibroblast-like synoviocytes in the intimal lining layer. Raised levels of STAT1
      are sustained in cultured RA compared with OA fibroblast-like synoviocytes, and
      STAT1 serine and tyrosine phosphorylation is rapidly induced upon stimulation
      with IFNbeta. CONCLUSION: These results demonstrate activation of the STAT1
      pathway in RA synovium by raised STAT1 protein expression and concomitantly
      increased tyrosine (701) and serine (727) phosphorylation. High expression of
      STAT1 is intrinsic to RA fibroblast-like synoviocytes in the intimal lining
      layer, whereas activation of the pathway by phosphorylation is an active process.

PMID- 14962956
TI  - Tenascin and aggrecan expression by articular chondrocytes is influenced by
      interleukin 1beta: a possible explanation for the changes in matrix synthesis
      during osteoarthritis.
AB  - OBJECTIVE: To analyse the distribution patterns of tenascin and proteoglycans in
      normal and osteoarthritic cartilage, and to determine the effect of interleukin
      1beta (IL1beta) on aggrecan and tenascin expression by human articular
      chondrocytes in vitro. METHODS: Normal and osteoarthritic cartilage and bone
      samples were obtained during total knee replacements or necropsies. After
      fixation and decalcification, paraffin embedded specimens were sectioned
      perpendicular to the surface. Specimens were graded according to Mankin and
      subdivided into those with normal, and mild, moderate, and severe osteoarthritic
      lesions. Serial sections were immunostained for tenascin. Tenascin expression by
      healthy and osteoarthritic chondrocytes was quantified by real time polymerase
      chain reaction (PCR). Furthermore, in cell culture experiments, human articular
      chondrocytes were treated with 0.1 or 10 ng/ml IL1beta. Real time PCR analyses of
      aggrecan and tenascin transcripts (normalised 18S rRNA) were conducted to
      determine the effect of IL1beta on later mRNA levels. RESULTS: Tenascin was
      immunodetected in normal and osteoarthritic cartilage. In osteoarthritic
      cartilage increased tenascin staining was found. Tenascin was found specifically
      in upper OA cartilage showing a strong reduction of proteoglycans. Greatly
      increased tenascin transcript levels were detected in osteoarthritic cartilage
      compared with healthy articular cartilage. IL1beta treatment of articular
      chondrocytes in vitro significantly increased tenascin transcripts (approximately
      200% of control) and strongly reduced aggrecan mRNA levels (approximately 42% of
      control). CONCLUSIONS: During progression of osteoarthritis the switch in matrix
      synthesis occurs mainly in upper osteoarthritic cartilage. Furthermore, changes
      in synthesis patterns of osteoarthritic chondrocytes may be significantly
      influenced by IL1beta, probably diffusing from the joint cavity within the upper
      osteoarthritic cartilage.

PMID- 14962957
TI  - Increased DNA fragmentation and ultrastructural changes in fibromyalgic muscle
      fibres.
AB  - OBJECTIVE: To determine whether there is evidence of increased DNA fragmentation
      and ultrastructural changes in muscle tissue of patients with fibromyalgia (FM)
      compared with healthy controls. METHODS: Muscle tissues from 10 community
      residents with FM and 10 age and sex matched healthy controls were examined
      "blindly" for the presence of DNA fragmentation by two different methods:
      terminal deoxynucleotidyl transferase (TdT) staining (TUNEL) and the FragEL
      Klenow DNA fragmentation detection kit. Ultrastructural analysis of tissue was
      performed by electron microscopy. RESULTS: DNA fragmentation was detected by both
      methods in 55.4 (SEM 2.5)% of the nuclei in muscle tissue of patients with FM
      compared with 16.1 (4.1)% (p<0.001) of the nuclei in healthy controls. Contrary
      to expectation, no typical features of apoptosis could be detected by electron
      microscopy. The myofibres and actin filaments were disorganised and lipofuscin
      bodies were seen; glycogen and lipid accumulation were also found. The number of
      mitochondria was significantly lower in patients with FM than in controls and
      seemed to be morphologically altered. CONCLUSION: The ultrastructural changes
      described suggest that patients with FM are characterised by abnormalities in
      muscle tissue that include increased DNA fragmentation and changes in the number
      and size of mitochondria. These cellular changes are not signs of apoptosis.
      Persistent focal contractions in muscle may contribute to ultrastructural tissue
      abnormalities as well as to the induction and/or chronicity of nociceptive
      transmission from muscle to the central nervous system.

PMID- 14962958
TI  - Characterisation of cartilage intermediate layer protein (CILP)-induced
      arthropathy in mice.
AB  - OBJECTIVES: To characterise cartilage intermediate layer protein (CILP)-induced
      arthropathy in mice. METHODS: The first and second halves of the nucleotide
      triphosphate pyrophosphohydrolase (NTPPHase) non-homologous region of human CILP
      were prepared as recombinant proteins (C1 and C2, respectively), including three
      overlapping fragments of C2 (C2F1, C2F2, and C2F3). C57BL/6 mice were immunised
      with these proteins to induce arthritis. In addition, a separate group of mice
      were immunised repeatedly with the mixture of C1 and C2 to see the effect of
      chronic immunisation. Arthritis developed in the mice, and cellular and humoral
      immune responses against CILP were analysed. RESULTS: Immunisation with C2 and
      with the mixture C2F1/C2F2/C2F3 caused the severest arthritis to develop in mice.
      Immunisation with one of C1, C2F1, C2F2, or C2F3 caused milder arthritis, even
      though each of the fragments carried T cell epitopes. Immunisation either with C1
      or C2 alone evoked cellular and humoral immune responses to both the C1 and C2
      proteins. Further, the repeated immunisation with the C1/C2 mixture caused tendon
      calcification and bone irregularity, together with decreased NTPPH activity.
      CONCLUSIONS: The results show that multiple T cell epitopes are needed for the
      development of CILP-induced arthritis, and present the characteristic new model
      of mild arthropathy accompanied by extra-articular calcifications. An immune
      response to putative murine CILP/NTPPH may be involved in the ectopic
      calcifications in the arthritic mice.

PMID- 14962959
TI  - Influence of radiographic phenotype on risk of hip osteoarthritis within
      families.
AB  - OBJECTIVE: To determine whether the magnitude of the genetic influence on the
      development of hip osteoarthritis (OA) varies according to the radiographic
      phenotype within families. PARTICIPANTS AND METHODS: 331 families in which at
      least one sibling (index participant) had undergone total hip replacement for OA
      and whose preoperative x ray findings were available; 505 siblings of these index
      participants, who have high exposure to genetic risk of hip OA; and 1718
      participants who had previously undergone intravenous urography, representative
      of the average general population exposure to genetic risk. Prevalence of hip OA
      was determined by individual radiographic features and minimum hip joint space.
      OA phenotype was partitioned according to pattern of femoral head migration and
      osteophyte bone response. Age adjusted odds ratios for hip OA in siblings,
      stratified according to phenotypic pattern in their index sibling, were assessed
      by unconditional logistic regression. RESULTS: The superior pattern of femoral
      head migration was more common in men, and the axial pattern more common in
      women. A poor bone response (absent osteophytosis) was associated with an
      indeterminate pattern of migration. The age adjusted odds ratios for definite hip
      OA were twofold higher in siblings of index participants who had no osteophyte
      response than in siblings whose index case had any degree of osteophyte (OR 2.05,
      95% CI 1.12 to 3.76). The risk of the siblings from these families having
      undergone hip replacement themselves was threefold higher. Patterns of migration
      and bone response were not concordant within families, even among same sex
      siblings. CONCLUSION: Careful phenotypic characterisation is essential for
      genetic studies of hip OA. The results of these studies are likely to be
      influenced by the phenotypic pattern of hip disease, particularly osteophyte bone
      response.

PMID- 14962960
TI  - How does tibial cartilage volume relate to symptoms in subjects with knee
      osteoarthritis?
AB  - BACKGROUND: No consistent relationship between the severity of symptoms of knee
      osteoarthritis (OA) and radiographic change has been demonstrated. OBJECTIVES: To
      determine the relationship between symptoms of knee OA and tibial cartilage
      volume, whether pain predicts loss of cartilage in knee OA, and whether change in
      cartilage volume over time relates to change in symptoms over the same period.
      METHOD: 132 subjects with symptomatic, early (mild to moderate) knee OA were
      studied. At baseline and 2 years later, participants had MRI scans of their knee
      and completed questionnaires quantifying symptoms of knee OA (knee-specific
      WOMAC: pain, stiffness, function) and general physical and mental health (SF-36).
      Tibial cartilage volume was determined from the MRI images. RESULTS: Complete
      data were available for 117 (89%) subjects. A weak association was found between
      tibial cartilage volume and symptoms at baseline. The severity of the symptoms of
      knee OA at baseline did not predict subsequent tibial cartilage loss. However,
      weak associations were seen between worsening of symptoms of OA and increased
      cartilage loss: pain (r(s) = 0.28, p = 0.002), stiffness (r(s) = 0.17, p = 0.07),
      and deterioration in function (r(s) = 0.21, p = 0.02). CONCLUSION: Tibial
      cartilage volume is weakly associated with symptoms in knee OA. There is a weak
      association between loss of tibial cartilage and worsening of symptoms. This
      suggests that although cartilage is not a major determinant of symptoms in knee
      OA, it does relate to symptoms.

PMID- 14962961
TI  - High prevalence of osteoarthritis 14 years after an anterior cruciate ligament
      tear in male soccer players: a study of radiographic and patient relevant
      outcomes.
AB  - OBJECTIVE: To identify the consequences of an anterior cruciate ligament (ACL)
      tear in a cohort of male soccer players 14 years after the initial injury with
      respect to radiographic knee osteoarthritis and patient relevant outcomes.
      METHODS: Of 219 male soccer players with an ACL injury in 1986, 205 (94%) were
      available for follow up after 14 years; 75% of the cohort (154/205) answered
      mailed questionnaires (KOOS, SF-36, and Lysholm knee scoring scale) and 122 of
      these consented to weight bearing radiographs. RESULTS: Radiographic changes were
      found in 95 (78%) of the injured knees, while more advanced changes, comparable
      with Kellgren-Lawrence grade 2 or higher, were seen in 50 (41%). In the uninjured
      knees more advanced changes, comparable with Kellgren-Lawrence grade 2 or higher,
      were seen in five knees (4%). No differences were seen between surgically and
      conservatively treated players. The patient relevant outcome was affected and did
      not differ between subjects with and without radiographic changes. Eighty per
      cent reported reduced activity level. CONCLUSIONS: A high prevalence of
      radiographic knee osteoarthritis was seen in male soccer players 14 years after
      an ACL disruption. The injury and the osteoarthritis, irrespective of the
      treatment provided to these patients, often result in knee related symptoms that
      severely affect the knee related quality of life by middle age.

PMID- 14962962
TI  - Radiological outcome after four years of early versus delayed treatment strategy
      in patients with recent onset rheumatoid arthritis.
AB  - OBJECTIVE: To determine the effect of different treatment strategies (early
      versus delayed) on the radiological progression of joint damage during 4 years.
      Additionally, to determine the effect of treatment strategy on the association of
      HLA class II alleles and joint damage. METHODS: Progression of radiographic
      damage and association of radiographic damage and genetic predisposition were
      compared in two cohorts, one treated according to the delayed treatment strategy
      (initial treatment with analgesics), the other treated according to the early
      treatment strategy (treatment with disease modifying antirheumatic drugs (DMARDs)
      chloroquine or sulfasalazine). Radiographic damage was measured by the modified
      Sharp-van der Heijde method. Genetic predisposition was determined by high
      resolution HLA-DR and DQ typing. RESULTS: A completers-only analysis of 153
      patients (originally 206 patients) in a non-randomised design showed less
      radiographic progression from 0 to 4 years in the early treatment group (median
      Sharp progression rate 1.3 points/year, n = 75) than in the delayed treatment
      group (2.5 points/year, n = 78) (p = 0.03). The progression from 1 to 4 years did
      not differ significantly between the groups. At 4 years, joint destruction in
      both groups was positively correlated with the presence of the shared epitope.
      CONCLUSIONS: The beneficial effect of early DMARD treatment on the radiological
      progression of joint damage is still present at 4 years. However, the rate of
      joint destruction from 1 to 4 years did not differ between the delayed and early
      treatment group. Neither the radiographic nor the immunogenetic data suggest that
      longlasting disease modification has been induced by early treatment.

PMID- 14962963
TI  - Polymorphisms in the tumour necrosis factor gene are not associated with severity
      of inflammatory polyarthritis.
AB  - BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a powerful inflammatory
      mediator in rheumatoid and other types of inflammatory arthritis. Polymorphisms
      within the TNFalpha gene have previously been investigated to determine their
      role in the aetiopathogenesis of rheumatoid arthritis (RA), but it is unclear
      whether reported associations are with susceptibility to, or severity of,
      disease. OBJECTIVE: To examine the association between both individual TNFalpha
      single nucleotide polymorphisms (SNPs) and haplotypes with the development and
      severity of erosions by 5 years in patients with inflammatory polyarthritis (IP).
      METHODS: 438 patients from the Norfolk Arthritis Register observational inception
      cohort of patients with IP were x rayed 5 years after disease onset. They were
      genotyped for nine SNPs mapping to the TNFalpha gene, using a SNaPshot primer
      extension assay. Haplotypes were constructed in patients with IP, who were
      compared for the presence and extent of erosions at 5 years. RESULTS: No
      association between individual TNFalpha SNPs or haplotypes in the patients who
      developed erosions at 5 years compared with those who remained non-erosive was
      found. Restricting analysis to patients who satisfied ACR criteria for RA by 5
      years did not affect the conclusions. CONCLUSION: The TNFalpha gene does not seem
      to be associated with severity as assessed by erosive outcome at 5 years in
      patients with IP.

PMID- 14962964
TI  - Reproducibility of bone mineral density measurement in daily practice.
AB  - BACKGROUND: Bone mineral density (BMD) measurements are frequently performed
      repeatedly for each patient. Subsequent BMD measurements allow reproducibility to
      be assessed. OBJECTIVE: To examine the reproducibility of BMD by dual energy x
      ray absorptiometry (DXA) and to investigate the practical value of different
      measures of reproducibility in a group of postmenopausal women. METHODS: Ninety
      five women, mean age 59.9 years, underwent two subsequent BMD measurements of
      spine and hip. Reproducibility was expressed as smallest detectable difference
      (SDD), coefficient of variation (CV), and intraclass correlation coefficient
      (ICC). Sources of variation were investigated by multilevel analysis. RESULTS:
      The median interval between measurements was 0 days (range 0-45). The mean
      difference (SD) between the measurements (g/cm(2)) was -0.001 (0.02) and -0.0004
      (0.02) at L1-4 and the total hip, respectively. At L1-4 and the total hip, SDD
      (g/cm(2)) was +/-0.05 and +/-0.04 and CV (%) was 1.92 and 1.59, respectively. The
      ICC at spine and hip was 0.99. CONCLUSIONS: Reproducibility in the postmenopausal
      women studied was good. In a repeated DXA scan a BMD change exceeding 2 radical
      2CV (%), the least significant change (LSC), or the SDD should be regarded as
      significant. Use of the SDD is preferable to use of the CV and LSC (%) because of
      its independence from BMD and its expression in absolute units. Expressed as SDD,
      a BMD change of at least +/-0.05 g/cm(2) at L1-4 and +/-0.04 g/cm(2) at the total
      hip should be considered significant.

PMID- 14962965
TI  - Fibromyalgia: a randomised, controlled trial of a treatment programme based on
      self management.
AB  - OBJECTIVE: To evaluate the efficacy of a treatment programme for patients with
      fibromyalgia (FM) based on self management, using pool exercises and education.
      METHODS: Randomised controlled trial with a 6 month follow up to evaluate an
      outpatient multidisciplinary programme; 164 patients with FM were allocated to an
      immediate 6 week programme (n = 84) or to a waiting list control group (n = 80).
      The main outcomes were changes in quality of life, functional consequences,
      patient satisfaction and pain, using a combination of patient questionnaires and
      clinical examinations. The questionnaires included the Fibromyalgia Impact
      Questionnaire (FIQ), Psychological General Well-Being (PGWB) index, regional pain
      score diagrams, and patient satisfaction measures. RESULTS: 61 participants in
      the treatment group and 68 controls completed the programme and 6 month follow up
      examinations. Six months after programme completion, significant improvements in
      quality of life and functional consequences of FM were seen in the treatment
      group as compared with the controls and as measured by scores on both the FIQ
      (total score p = 0.025; fatigue p = 0.003; depression p = 0.031) and PGWB (total
      score p = 0.032; anxiety p = 0.011; vitality p = 0.013,). All four major areas of
      patient satisfaction showed greater improvement in the treatment than the control
      groups; between-group differences were statistically significant for "control of
      symptoms", "psychosocial factors", and "physical therapy" No change in pain was
      seen. CONCLUSION: A 6 week self management based programme of pool exercises and
      education can improve the quality of life of patients with FM and their
      satisfaction with treatment. These improvements are sustained for at least 6
      months after programme completion.

PMID- 14962966
TI  - Interstitial lung disease, a common manifestation of newly diagnosed polymyositis
      and dermatomyositis.
AB  - OBJECTIVES: To estimate the prevalence and predictors of interstitial lung
      disease in newly diagnosed polymyositis and dermatomyositis. METHODS: A
      prospective study in which consecutive patients with newly diagnosed poly- and
      dermatomyositis, regardless of clinical symptoms of pulmonary disease, were
      investigated with chest x ray, high resolution computed tomography (HRCT),
      pulmonary function tests, and biochemical and autoantibody analysis. Patients
      with inclusion body myositis, malignancy, other defined inflammatory connective
      tissue diseases (CTDs), or antibody profile indicating other CTDs were excluded.
      RESULTS: Between March 1998 and September 2000, 26 new cases of poly- or
      dermatomyositis were diagnosed; 17 of those patients were included in the study.
      Interstitial lung disease (ILD), defined as radiological signs on chest x ray
      examination/HRCT or restrictive ventilatory defect, were found in 11 (65%)
      patients and were more common in men than in women. Arthritis and occurrence of
      anti-Jo-1 antibodies were found more often in patients with ILD than in those
      without. There was no statistically significant association between respiratory
      symptoms, other serological or laboratory variables and ILD. CONCLUSIONS: ILD is
      a common early manifestation in patients with poly- and dermatomyositis and is
      not always related to clinical symptoms. Chest x ray examination, HRCT, pulmonary
      function tests, and analysis of anti-Jo-1 antibodies should be included in the
      initial investigation of patients with myositis regardless of respiratory
      symptoms.

PMID- 14962967
TI  - Arthrographic joint distension with saline and steroid improves function and
      reduces pain in patients with painful stiff shoulder: results of a randomised,
      double blind, placebo controlled trial.
AB  - OBJECTIVE: To determine whether arthrographic distension with a mixture of saline
      and steroid, in patients with painful stiff shoulder for at least 3 months, is
      better than placebo in improving function, pain, and range of motion at 3, 6, and
      12 weeks. METHODS: A randomised, placebo controlled trial with participant and
      outcome assessor blinding in which shoulder joint distension with normal saline
      and corticosteroid was compared with placebo (arthrogram). Outcome measures,
      assessed at 3, 6, and 12 weeks, included a shoulder-specific disability measure
      (SPADI), a patient preference measure (Problem Elicitation Technique (PET)),
      pain, and range of active motion. RESULTS: From 96 potential participants, 48
      were recruited. Four withdrew from the placebo group after the 3 week assessment
      and three subsequently received arthrographic distension with saline and steroid.
      At 3 weeks, significantly greater improvement in SPADI (p = 0.005), PET, overall
      pain, active total shoulder abduction, and hand behind back was found in
      participants in the joint distension and steroid group than in the placebo group.
      At 6 weeks the results of the intention to treat analysis favoured joint
      distension, although the between-group differences were only significant for
      improvement in PET (difference in mean change in PET between groups = 45.9 (95%
      CI 3.2 to 88.7). Excluding the four withdrawals, the between-group differences
      for the disability and pain measures significantly favoured distension over
      placebo. At 12 weeks, both the intention to treat analysis and an analysis
      excluding the four withdrawals demonstrated a significantly greater improvement
      in PET score for the distension group. CONCLUSIONS: Short term efficacy of
      arthrographic distension with normal saline and corticosteroid over placebo was
      demonstrated in patients with painful stiff shoulder.

PMID- 14962968
TI  - The dinucleotide repeat polymorphism in the 3'UTR of the CD154 gene has a
      functional role on protein expression and is associated with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To investigate the association of the (CA)n dinucleotide repeat in the
      3' untranslated region (3'UTR) of the CD154 gene with systemic lupus
      erythematosus (SLE), and its functional role in protein expression. METHODS: The
      allelic and genotypic distributions of the polymorphism were compared in 80
      patients with SLE and 80 controls. A complete clinical and analytical database
      was recorded in each patient in order to correlate the clinical manifestations in
      SLE with different alleles. To investigate the functional role of the
      polymorphism, the CD154 protein expression on activated lymphocytes from healthy
      homozygous controls was evaluated by flow cytometry. RESULTS: The 24 CA allele
      was the most represented in controls (p = 0.029), whereas the alleles containing
      >24 CA repeats were found in patients (p = 0.0043). Furthermore, when only
      homozygous women were considered, most controls carried two 24 CA alleles (p =
      0.041), whereas most patients carried two alleles containing >24 CA repeats (p =
      0.032). Also, patients carrying at least one 24 CA allele had less neurological
      involvement (p = 0.034), and carriers of at least one allele with fewer than 24
      CA repeats presented more livedo reticularis (p = 0.006) and anti-Sm (p = 0.01)
      and anti-RNP (p = 0.038) autoantibodies. CD154 maximum expression in activated
      lymphocytes from all controls was reached after 54 hours, but it was more
      prolonged in controls carrying two alleles with >24 CA repeats (p = 0.0068).
      CONCLUSION: The CD154 3'UTR microsatellite is associated with SLE, and the most
      represented alleles in patients were accompanied by a more prolonged protein
      expression in activated lymphocytes from controls.

PMID- 14962969
TI  - Tumour necrosis factor alpha inhibitor treatment for sarcoidosis refractory to
      conventional treatments: a report of five patients.
AB  - OBJECTIVE: To study the effectiveness of tumour necrosis factor alpha (TNFalpha)
      inhibitor treatment for sarcoidosis refractory to conventional treatments.
      METHODS: Five patients (two men, three women) were treated with infliximab. All
      patients received a loading dose of 3 mg/kg at 0, 2, and 6 weeks and then
      maintenance infusions every 4-8 weeks. Patients had their dose increased or the
      dosing interval reduced when the disease relapsed. These patients had active
      disease despite treatment with corticosteroids and other immunomodulatory agents.
      All patients had a negative tuberculin skin test. RESULTS: Sarcoidosis in all
      patients improved significantly without any serious adverse reactions.
      CONCLUSION: This study suggests that TNFalpha is effective in patients for whom
      conventional treatment fails.

PMID- 14962970
TI  - Combined intravenous methotrexate and cyclophosphamide for refractory childhood
      lupus nephritis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of combining monthly intravenous
      methotrexate (IV MTX) with monthly IV cyclophosphamide (CYTX; given on the same
      day) for the treatment of children who develop recurrent diffuse proliferative
      glomerulonephritis secondary to systemic lupus erythematosus during or after the
      standard 3 year course of IV CYTX. METHODS: Five children were treated with nine
      monthly doses of IV CYTX (750-1000 mg/m(2)/month) and IV MTX (50-300
      mg/m(2)/month) given on the same day. Their clinical and laboratory measurements
      were collected every other week throughout the nine months. RESULTS: All children
      improved dramatically. SLEDAI scores decreased from an average of 13.8 to 4.4,
      mean (SD) serum creatinine level fell from 100 (60) to 80 (40) micro mol/l, and
      serum albumin rose from 28 (11) g/l to 41 (6) g/l, while the mean (SD) C3 level
      increased from 0.5 (0.1) g/l to 0.9 (0.4) g/l. Clinical improvement persisted
      after 4 years' follow up despite discontinuing MTX and CYTX after 9 months. The
      average daily dose of corticosteroids has been reduced from 27.6 mg/day at the
      start of treatment to 12.5 mg/day at follow up. CONCLUSION: Combined IV MTX and
      IV CYTX treatment effectively controls recurrent or refractory lupus nephritis in
      children with significant disease activity after treatment with IV CYTX alone.

PMID- 14962971
TI  - Prevention of glucocorticoid osteoporosis: a consensus document of the Dutch
      Society for Rheumatology.

PMID- 14962972
TI  - Does long term treatment with azathioprine predispose to malignancy and death in
      patients with systemic lupus erythematosus?

PMID- 14962973
TI  - Bone mineral density in patients with systemic sclerosis.

PMID- 14962974
TI  - Adoptive transfer of alveolar macrophages abrogates bronchial
      hyperresponsiveness.
AB  - Increasing evidence suggests that alveolar macrophages (AM) are involved in
      asthma pathogenesis. To better understand the role that these cells play, we
      investigated the capacity of AM from allergy-resistant rat, Sprague Dawley (SD),
      to modulate airway hyperresponsiveness of allergy-susceptible rat, Brown Norway
      (BN). AM of ovalbumin (OVA)-sensitized BN rats were eliminated by intratracheal
      instillation of liposomes containing clodronate. AM from OVA-sensitized SD rats
      were transferred into AM-depleted BN rats 24 h before allergen challenge. Airway
      responsiveness to methacholine was measured the following day. Instillation of
      liposomes containing clodronate in BN rats eliminated 85% AM after 3 d compared
      with saline liposomes. Methacholine concentration needed to increase lung
      resistance by 200% (EC200RL) was significantly lower in OVA-challenged BN rats
      (27.9 +/- 2.8 mg/ml) compared with SD rats (63.9 +/- 8.6 mg/ml). However, when AM
      from SD rats were transferred into AM-depleted BN rats, airway responsiveness
      (64.0 +/- 11.3 mg/ml) was reduced to the level of naive rats (54.4 +/- 3.7 mg/ml)
      in a dose-dependent manner. Interestingly, transfer of AM from BN rats into SD
      rats did not modulate airway responsiveness. To our knowledge, this is the first
      direct evidence showing that AM may protect against the development of airway
      hyperresponsiveness.

PMID- 14962975
TI  - High levels of catalase and glutathione peroxidase activity dampen H2O2 signaling
      in human alveolar macrophages.
AB  - Results are presented which support the hypothesis that adequate steady-state
      levels of hydrogen peroxide (H2O2) are required to overcome the effects of high
      catalase and glutathione peroxidase (GPx) expression for p38 mitogen-activated
      protein (MAP) kinase activation and tumor necrosis factor (TNF)-alpha gene
      expression in human alveolar macrophages stimulated with asbestos. We found
      significant differences in the types and amounts of reactive oxygen species
      generated in human blood monocytes compared with human alveolar macrophages. This
      difference in reactive oxygen species production is related, in part, to the
      differences in antioxidant enzyme expression and activity. Most importantly,
      catalase and GPx activities were significantly increased in alveolar macrophages
      compared with blood monocytes. Asbestos activated the p38 MAP kinase and induced
      TNF-alpha gene expression only in blood monocytes. Increasing the steady-state
      levels of H2O2 by using polyethylene glycol superoxide dismutase, an antioxidant
      that crosses the cell membrane, or aminotriazole, an irreversible inhibitor of
      catalase, allowed the p38 MAP kinase to be activated in alveolar macrophages. In
      addition, asbestos-stimulated macrophages cultured with polyethylene glycol
      superoxide dismutase had a significant increase in gene expression mediated by
      the TNF-alpha promoter. These results demonstrate that high catalase and GPx
      activity in human alveolar macrophages limits the effectiveness of H2O2 to act as
      a mediator of inflammatory gene expression.

PMID- 14962976
TI  - Activating and silencing histone modifications form independent allelic switch
      regions in the imprinted Gnas gene.
AB  - Activation and suppression of gene transcription is tightly controlled by
      epigenetic modifications. The imprinted Gnas1 gene region contains closely
      juxtaposed maternally expressed (Nesp) and paternally expressed (Nespas, Gnasxl,
      Exon 1A) transcripts, providing a unique opportunity to study how epigenetic
      modifications change in nucleosomes from active to silenced promoters. Using 30
      polymorphic sites across the Gnas1 gene region in (C57BL/6JxMus spretus) F(1)
      mice and chromatin immunoprecipitation (ChIP) assays we identified two allelic
      switch regions (ASRs) that mark boundaries of epigenetic information. We show
      that activating signals (histone acetylation and methylation of H3 Lys4) and
      silencing signals (histone methylation of H3 Lys9 and DNA methylation) segregate
      independently across the ASRs and suggest that these ASRs allow the
      transcriptional elongation to proceed through the silenced domain of nearby
      imprinted promoters. We discuss these findings in light of recent progress in the
      conceptualization of nucleosome remodeling during transcriptional elongation and
      in the development of histone code.

PMID- 14962977
TI  - Striatal cells from mutant huntingtin knock-in mice are selectively vulnerable to
      mitochondrial complex II inhibitor-induced cell death through a non-apoptotic
      pathway.
AB  - Extensive striatal neuronal loss occurs in Huntington's disease (HD), which is
      caused by an expanded polyglutamine tract in huntingtin (htt). Evidence suggests
      that mutant htt directly or indirectly compromises mitochondrial function,
      contributing to the neuronal loss. To determine the role of compromised
      mitochondrial function in the neuronal cell death in HD, immortalized striatal
      cells established from Hdh(Q7) (wild-type) and Hdh(Q111) (mutant) mouse knock-in
      embryos were treated with 3-nitropropionic acid (3-NP), a mitochondrial complex
      II toxin. 3-NP treatment caused significantly greater cell death in mutant
      striatal cells compared with wild-type cells. In contrast, the extent of cell
      death induced by rotenone, a complex I inhibitor, was similar in both cell lines.
      Although evidence of apoptosis was present in 3-NP-treated wild-type striatal
      cells, it was absent in 3-NP-treated mutant cells. 3-NP treatment caused a
      greater loss of mitochondrial membrane potential (deltapsim) in mutant striatal
      cells compared with wild-type cells. Cyclosporine A, an inhibitor of
      mitochondrial permeability transition pore (PTP), and ruthenium red, an inhibitor
      of the mitochondrial calcium uniporter, both rescued mutant striatal cells from 3
      NP-induced cell death and prevented the loss of deltapsim. These data show that
      mutant htt specifically increases cell vulnerability to mitochondrial complex II
      inhibition and further switched the type of cell death induced by complex II
      inhibition from apoptosis to a non-apoptotic form, caused by mitochondrial
      membrane depolarization, probably initiated by mitochondrial calcium overload and
      subsequent PTP opening. These findings suggest that impaired mitochondrial
      complex II function in HD may contribute to non-apoptotic neuronal cell death.

PMID- 14962978
TI  - CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation.
AB  - Molecular chaperones, ubiquitin ligases and proteasome impairment have been
      implicated in several neurodegenerative diseases, including Alzheimer's and
      Parkinson's disease, which are characterized by accumulation of abnormal protein
      aggregates (e.g. tau and alpha-synuclein respectively). Here we report that CHIP,
      an ubiquitin ligase that interacts directly with Hsp70/90, induces ubiquitination
      of the microtubule associated protein, tau. CHIP also increases tau aggregation.
      Consistent with this observation, diverse of tau lesions in human postmortem
      tissue were found to be immunopositive for CHIP. Conversely, induction of Hsp70
      through treatment with either geldanamycin or heat shock factor 1 leads to a
      decrease in tau steady-state levels and a selective reduction in detergent
      insoluble tau. Furthermore, 30-month-old mice overexpressing inducible Hsp70 show
      a significant reduction in tau levels. Together these data demonstrate that the
      Hsp70/CHIP chaperone system plays an important role in the regulation of tau
      turnover and the selective elimination of abnormal tau species. Hsp70/CHIP may
      therefore play an important role in the pathogenesis of tauopathies and also
      represents a potential therapeutic target.

PMID- 14962979
TI  - Quantitative genetic variation: a post-modern view.
AB  - It has become commonplace to map individual quantitative trait loci (QTL) in
      experimental organisms; the means (line-crosses and dense maps of markers) and
      motivation (the close relationship between continuous physiological traits and
      common, complex diseases) are self-evident. Progress in mapping human QTL has
      been more gradual, an inevitable consequence of genetic mapping in a natural
      population setting. The common objective of these studies has been to understand
      the molecular mechanisms underlying individual QTL. Recent theoretical and
      practical advances shift this focus to a more comprehensive or genomic
      perspective on quantitative variation. Fisher's infinitesimal model of adaptive
      evolution, which satisfied quantitative geneticists for over 50 years, has been
      modified in the light of data from QTL mapping experiments in plants and animals.
      The resulting exponential model provides a pleasing empirical fit to the
      distribution of QTL effect sizes, predicts that a large amount of quantitative
      variation will be explained by a limited number of genes and suggests a new
      mathematical framework for linkage mapping. Molecular analysis of QTL suggests
      that coding variants (e.g. allozymes) underlie a fraction of quantitative
      variation and that variants that affect gene expression (expression QTL, eQTL)
      have a substantial role. This is supported by genomic experiments that combine
      expression profiling with classical genetic mapping approaches to reveal a
      remarkable wealth of quantitative heritable variation in the transcriptome and
      that cis-and trans-acting regulatory factors are organized in networks reflecting
      pleiotropy. It is hoped that these advances will enhance our understanding of the
      genetic basis of complex inherited diseases.

PMID- 14962980
TI  - Control elements within the PWS/AS imprinting box and their function in the
      imprinting process.
AB  - A cluster of imprinted genes on human chromosome 15q11-q13 (the PWS/AS domain)
      and its ortholog on mouse chromosome 7c is believed to be regulated by an
      imprinting control center. Although minideletions in this region in Angelman
      syndrome (AS) and Prader-Willi syndrome (PWS) patients revealed that two
      elements, shortest deletion regions of overlap in AS families and PWS families
      (AS-SRO and PWS-SRO), respectively, constitute the IC, the molecular mechanism
      that governs this regional control remains obscure. To understand how this
      imprinting center works, a mouse model was sought. The striking similarity
      between the human and mouse sequences allowed the generation of a minitransgene
      (AS-SMP) composed of AS-SRO and the Snrpn minimal promoter (SMP) the mouse
      ortholog of PWS-SRO. This minitransgene carries out, in a highly reliable and
      reproducible manner, all steps of the imprinting process. In an attempt to
      decipher the molecular mechanism of the imprinting process, we generated and
      tested for imprinting five minitransgenes based on AS-SMP, in which various parts
      of the 160 bp SMP were deleted. These experiments revealed a set of five cis
      elements that carry out the various steps of the imprinting process. This set
      includes: (i). two copies of a de novo methylation signal (DNS) that establish
      the maternal imprint during oogenesis; (ii). an allele discrimination signal that
      establishes the paternal imprint; and (iii). two elements that act together to
      maintain the paternal imprint. Two functionally redundant sets of the five
      elements were found on the respective endogenous mouse sequence explaining the
      previously published contradictory results of targeted deletion experiments.
      Together with the fact that all five elements bind specific proteins that are
      presumably the factors acting in trans in the imprinting process, our
      observations set the stage for a comprehensive study of the molecular mechanism
      involved in the control of the imprinting process.

PMID- 14962981
TI  - Amino-acid changes acquired during evolution by olfactory receptor 912-93 modify
      the specificity of odorant recognition.
AB  - The sense of smell in mammals can perceive and discriminate a wide variety of
      volatile odorants. Odorants bind to specific olfactory receptors (ORs) to
      initiate an action potential that transduces olfactory information to the
      olfactory cortex. We previously identified the structural motifs of odorant
      molecules (aliphatic 2- or 3-ketones) required to activate mouse OR912-93 by
      detection of the odorant response using calcium measurement in transfected cells.
      In order to study changes in the specificity of this receptor that might have
      occurred during evolution, we cloned the orthologous genes from six primate
      species and pig and assayed the encoded receptors for responses to odorants.
      Primate OR912-93 orthologs share 88-97% sequence identity. All the receptors
      responded to 2- and 3-heptanone except the squirrel-monkey OR, which responded
      only to 3-heptanone, and the human and orangutan ORs, which were not functional.
      Directed mutagenesis allowed us to convert the squirrel-monkey response to that
      of the other functional 912-93 ORs by substituting three amino acids in the
      second extracellular loop. Orangutan and human 912-93 ORs regained function after
      restoration of the arginine residue in the DRY motif required for G-protein
      activation. However, the human receptor was constitutively activated in the
      absence of ligand stimulation. Using natural mutants of the OR912-93 receptor, we
      provide evidence that squirrel-monkeys evolved towards a restriction of the
      specificity of this receptor and therefore that slight alterations in the
      sequence of a receptor can induce subtle changes in recognition specificity.

PMID- 14962982
TI  - ZZ domain is essentially required for the physiological binding of dystrophin and
      utrophin to beta-dystroglycan.
AB  - An intracellular protein, dystrophin, plays an important role in keeping muscle
      fibers intact by binding at its N-terminal end to the subsarcolemmal cytoskeletal
      actin network and via its C-terminal end to the transmembraneous protein beta
      dystroglycan. Duchenne muscular dystrophy is caused by the loss of dystrophin,
      which can result from the loss of this binding. The N-terminal part of the latter
      binding site of dystrophin has been well documented using overlay assay and X-ray
      diffraction assays. However, the binding site at the C-terminal region of
      dystrophin has not been examined in detail. In the present work, we report a
      detailed analysis of the C-terminal binding domain as follows. (1). The full
      binding activity corresponding to the effective binding in vivo is expressed by
      the dystrophin fragment spanning amino acids 3026-3345 containing the ZZ domain
      at the C-terminus. Determination of this binding range is important not only for
      understanding of the mechanism of dystrophy, but also useful for the design of
      truncated dystrophin constructs for gene therapy. (2). The ZZ domain binds to EF1
      domain in the dystrophin fragment to reinforce the binding activity. (3). The
      cysteine 3340 in the ZZ domain is essential for the binding of dystrophin to beta
      dystroglycan. A reported case of DMD due to missense mutation C3340Y may be
      caused by inability to fix dystrophin beneath the cell membrane. (4). The binding
      mode of utrophin is different from that of dystrophin. The difference is
      conspicuous concerning the cysteine residues present in the ZZ domain.

PMID- 14962983
TI  - Spontaneous differentiation of germ cells from human embryonic stem cells in
      vitro.
AB  - Little is known of molecular requirements for specification of human germ cells.
      However, it is likely that they are specified through the action of sequentially
      expressed genes just as in model organisms. We sought to determine whether human
      embryonic stem (ES) cell lines, like those of mice, might be capable of forming
      germ cells in vitro. We compared transcriptional profiles of three pluripotent
      human ES cells to those of isolated inner cell mass (ICM) cells. We found that
      ICM cells expressed NANOS1, STELLAR and OCT4, whereas undifferentiated human ES
      cells expressed these genes along with the germ cell-specific gene, DAZL. Upon ES
      cell differentiation into embryoid bodies (EBs), we observed a shift in
      expression from RNA and protein markers of immature germ cells to those
      indicative of mature germ cells, including expression of VASA, BOL, SCP1, SCP3,
      GDF9 and TEKT1. Although ability to test the function of these putative VASA
      positive germ cells is limited, these results demonstrate that differentiation of
      human ES cells into EBs in vitro results in formation of cells that express
      markers specific to gonocytes.

PMID- 14962984
TI  - The multiassembly problem: reconstructing multiple transcript isoforms from EST
      fragment mixtures.
AB  - Recent evidence of abundant transcript variation (e.g., alternative splicing,
      alternative initiation, alternative polyadenylation) in complex genomes indicates
      that cataloging the complete set of transcripts from an organism is an important
      project. One challenge is the fact that most high-throughput experimental methods
      for characterizing transcripts (such as EST sequencing) give highly detailed
      information about short fragments of transcripts or protein products, instead of
      a complete characterization of a full-length form. We analyze this "multiassembly
      problem"-reconstructing the most likely set of full-length isoform sequences from
      a mixture of EST fragment data-and present a graph-based algorithm for solving
      it. In a variety of tests, we demonstrate that this algorithm deals appropriately
      with coupling of distinct alternative splicing events, increasing fragmentation
      of the input data and different types of transcript variation (such as
      alternative splicing, initiation, polyadenylation, and intron retention). To test
      the method's performance on pure fragment (EST) data, we removed all mRNA
      sequences, and found it produced no errors in 40 cases tested. Using this
      algorithm, we have constructed an Alternatively Spliced Proteins database (ASP)
      from analysis of human expressed and genomic sequences, consisting of 13,384
      protein isoforms of 4422 genes, yielding an average of 3.0 protein isoforms per
      gene.

PMID- 14962986
TI  - Correct estimation of preferential chromosome pairing in autotetraploids.
AB  - In recent work, a statistical model was proposed for the purpose of estimating
      parameters associated with quantitative trait locus (QTL) mapping and
      preferential pairing within a polyploidy framework. The statistical model
      contained several parameters that, when estimated from experimental data,
      supplied information about QTL, including a preferential pairing factor. Among
      the results reported were estimates of preferential pairing, many of which
      indicated high levels of preferential pairing (p = 0.60) that were inconsistent
      with biological expectations. By using the biological inconsistencies as our
      motivation, we present a reformulated statistical method for estimating
      preferential pairing, and use this method to reanalyze the same autotetraploid
      alfalfa data and to conduct a simulation study. Our results directly contradict
      the current findings of significant preferential pairing and affirm the
      traditional view of random chromosome segregation in alfalfa.

PMID- 14962988
TI  - Noncoding sequences conserved in a limited number of mammals in the SIM2 interval
      are frequently functional.
AB  - Cross-species DNA sequence comparison is a fundamental method for identifying
      biologically important elements, because functional sequences are evolutionarily
      conserved, wheres nonfunctional sequences drift. A recent genome-wide comparison
      of human and mouse DNA discovered over 200,000 conserved noncoding sequences with
      unknown function. Multispecies DNA comparison has been proposed as a method to
      prioritize these conserved noncoding sequences for functional analysis based on
      the hypothesis that elements present in many species are more likely to be
      functional than elements present in limited numbers of species. Here, we perform
      a comparative analysis of the single-minded 2 (SIM2) gene interval on human
      chromosome 21 with horse, cow, pig, dog, cat, and mouse DNA. We classify
      conserved sequences based on the number of mammals in which they are present, and
      experimentally test sequences in each class for function. As hypothesized,
      conserved sequences present in many mammals are frequently functional.
      Additionally, we demonstrate that sequences conserved in a limited number of
      mammals are also frequently functional. Examination of genomic deletions in
      chimpanzee and rhesus macaque DNA showed that several putatively functional
      conserved noncoding human sequences were absent in these primates. These findings
      suggest that functional conserved noncoding human sequences can be missing in
      other mammals, even closely related primate species.

PMID- 14962989
TI  - Anomalies in the expression profile of interspecific hybrids of Drosophila
      melanogaster and Drosophila simulans.
AB  - When females of Drosophila melanogaster and males of Drosophila simulans are
      mated, the male progeny are inviable, whereas the female progeny display manifold
      malformations and are sterile. These abnormalities result from genetic
      incompatibilities accumulated since the time the lineages of the species
      diverged, and may have their origin in aberrant gene transcription. Because
      compensatory changes within species may obscure differences at the regulatory
      level in conventional comparisons of the expression profile between species, we
      have compared the gene-expression profile of hybrid females with those of females
      of the parental species in order to identify regulatory incompatibilities. In the
      hybrid females, we find abnormal levels of messenger RNA for a large fraction of
      the Drosophila transcriptome. These include a gross underexpression of genes
      preferentially expressed in females, accompanying gonadal atrophy. The hybrid
      females also show significant overexpression of male-biased genes, which we
      attribute to incompatibilities in the regulatory mechanisms that normally act to
      control the expression of these genes in females. The net result of the multiple
      incompatibilities is that the gene-expression profiles of the parental females
      are more similar to each other than either is to that of the hybrid.

PMID- 14962990
TI  - Nitric oxide donor increases osteoprotegerin production and osteoclastogenesis
      inhibitory activity in bone marrow stromal cells from ovariectomized rats.
AB  - Nitric oxide (NO) has emerged as a potent regulator useful in alleviating
      estrogen deficiency bone loss. Osteoprotegerin (OPG) and receptor activator of
      nuclear factor-kappaB ligand (RANKL) play important roles in regulating
      osteoclastogenesis. Although recent studies have reported NO donor attenuation of
      bone loss, the effect of NO donor on OPG and RANKL expression of osteogenic
      stromal cells and bone microenvironment in ovariectomized rats is not fully
      understood. Here, we showed that optimal NO donor treatment [2,2'
      (hydroxynitrosohydrazino)bis-ethanamine; 15 microm] increased OPG, but not RANKL,
      levels in bone marrow stromal cells from ovariectomized rats. NO donor
      augmentation of OPG synthesis was transcriptionally mediated. The stimulatory
      action of NO donor on OPG expression appeared to be regulated by tyrosine kinase
      dependent activation of Cbfa1/Runx2 binding to the OPG promoter, because cell
      cultures pretreated with tyrosine kinase inhibitor (herbimycin A), but not with
      protein kinase A inhibitor (calphostain C) or protein kinase C inhibitor [(Rp)
      cAMP] significantly reduced NO-augmented Runx2 activation and OPG levels.
      Conditioned medium from NO donor-treated cells inhibited macrophage-colony
      stimulating factor and RANKL-induced osteoclast formation of macrophage-colony
      stimulating factor-dependent bone marrow macrophages. Neutralization with anti
      OPG antibodies abolished the inhibitory effect of conditioned medium on
      osteoclastogenesis. Immunohistochemical observation also showed that 2,2'
      (hydroxynitrosohydrazino)bis-ethanamine increased OPG expression of osteochondral
      cells located at metaphyseal endosteum and calcified cartilage of proximal femurs
      in ovariectomized rats. These findings suggest that NO donor can be an
      alternative pharmacological strategy for regulating bone resorption.

PMID- 14962985
TI  - Numerous novel annotations of the human genome sequence supported by a 5'-end
      enriched cDNA collection.
AB  - A collection of 90,000 human cDNA clones generated to increase the fraction of
      "full-length" cDNAs available was analyzed by sequence alignment on the human
      genome assembly. Five hundred fifty-two gene models not found in LocusLink, with
      coding regions of at least 300 bp, were defined by using this collection. Exon
      composition proposed for novel genes showed an average of 4.7 exons per gene. In
      20% of the cases, at least half of the exons predicted for new genes coincided
      with evolutionary conserved regions defined by sequence comparisons with the
      pufferfish Tetraodon nigroviridis. Among this subset, CpG islands were observed
      at the 5' end of 75%. In-frame stop codons upstream of the initiator ATG were
      present in 49% of the new genes, and 16% contained a coding region comprising at
      least 50% of the cDNA sequence. This cDNA resource also provided candidate small
      protein-coding genes, usually not included in genome annotations. In addition,
      analysis of a sample from this cDNA collection indicates that approximately 380
      gene models described in LocusLink could be extended at their 5' end by at least
      one new exon. Finally, this cDNA resource provided an experimental support for
      annotations based exclusively on predictions, thus representing a resource
      substantially improving the human genome annotation.

PMID- 14962991
TI  - Tacrolimus impairment of insulin secretion in isolated rat islets occurs at
      multiple distal sites in stimulus-secretion coupling.
AB  - Tacrolimus causes posttransplant diabetes mellitus, although the pathogenetic
      mechanisms remain controversial. We studied the mechanism of tacrolimus-induced
      impairment of insulin secretion using isolated rat pancreatic islets. Tacrolimus
      caused reductions in DNA and insulin contents per islet during 7-d culture.
      Tacrolimus time-dependently suppressed glucose-stimulated insulin secretion, and
      at a therapeutic concentration of 0.01 micromol/liter, it suppressed glucose
      stimulated insulin secretion to 32 +/- 5% of the control value after 7-d
      incubation. Tacrolimus did not change islet glucose utilization and oxidation,
      ATP production, insulin mRNA expression, or the capacity for high glucose to
      increase intracellular Ca(2+), but altered the rapid frequency oscillations of
      Ca(2+) concentration. Tacrolimus suppressed insulin secretion stimulated by
      mitochondrial fuel (combination of l-leucine and l-glutamine, and alpha
      ketoisocaproate) and glibenclamide, but not by l-arginine. Tacrolimus suppressed
      insulin secretion induced by carbachol and by a protein kinase C agonist in the
      presence or absence of extracellular Ca(2+). Under stringent Ca(2+)-free
      conditions, tacrolimus did not affect mastoparan-induced insulin secretion, but
      suppressed its glucose augmentation. Our results suggest that tacrolimus impairs
      glucose-stimulated insulin secretion downstream of the rise in intracellular
      Ca(2+) at insulin exocytosis, and that protein kinase C-mediated (Ca(2+)
      dependent and independent) and Ca(2+)-independent GTP signaling pathways may be
      involved. However, tacrolimus-induced impaired insulin secretion was reversed 3 d
      after removal of the drug. Our study demonstrated that tacrolimus impairs insulin
      secretion at multiple steps in stimulus-secretion coupling.

PMID- 14962992
TI  - In vitro increase in intracellular calcium concentrations induced by low or high
      extracellular glucose levels in ependymocytes and serotonergic neurons of the rat
      lower brainstem.
AB  - Pancreatic glucokinase (GK)-like immunoreactivities are located in ependymocytes
      and serotonergic neurons of the rat brain. The present study investigated in
      vitro changes in intracellular calcium concentrations ([Ca(2+)](i)) in response
      to low (2 mm) or high (20 mm) extracellular glucose concentrations in isolated
      cells from the wall of the central canal (CC), raphe obscurus nucleus (ROb),
      ventromedial hypothalamus (VMH), and lateral hypothalamic area (LHA) in male
      rats. An increase in [Ca(2+)](i) was found in cells from the CC (21.1% or 9.8% of
      ependymocytes), ROb (10.9% or 14.5% of serotonergic neurons), VMH (7.8% and 25.2%
      of neurons), and LHA (20% or 15.7% of neurons), when extracellular glucose levels
      were changed from 10 to either 2 or 20 mm, respectively. Most of the
      ependymocytes and serotonergic neurons responding to the glucose changes were
      immunoreactive to the anti-GK in the CC (96.8% for low glucose and 100% for high
      glucose) and ROb (100% for low and high glucose). The [Ca(2+)](i) increase was
      blocked with calcium-free medium or L-type calcium channel blocker. Cells with an
      increase in [Ca(2+)](i) in response to low glucose did not respond to high
      glucose and vice versa. Inhibition of GK activity with acute alloxan treatment
      blocked low or high glucose-induced [Ca(2+)](i) increases in most GK
      immunoreactive cells from the CC or ROb. The glucose-sensitive [Ca(2+)](i)
      increase in neurons of the VMH and LHA was also alloxan-sensitive, but no cells
      taken from the VMH and LHA were immunoreactive to the antibody used. The present
      study further indicates that ependymocytes of the CC and serotonergic neurons in
      the ROb are also sensitive to the changes in extracellular glucose in a GK
      dependent manner, but that the subtype of GK in these cells could be different
      from that in the VMH and LHA.

PMID- 14962993
TI  - Interaction between corticosterone and insulin in obesity: regulation of lard
      intake and fat stores.
AB  - Passive elevations in glucocorticoids result in increased insulin and abdominal
      obesity with peripheral wasting, as observed in Cushing's syndrome, with little
      effect on chow intake. In the absence of insulin (streptozotocin-induced
      diabetes) diabetic rats markedly increase their chow intake in proportion to
      glucocorticoids. Given a choice of lard or chow, diabetic rats first eat lard,
      then reduce caloric intake to normal for 48 h before returning to hyperphagia on
      chow alone. We performed three experiments to determine the relationship of
      corticosterone and insulin to lard intake, chow intake, body weight, hormones,
      and fat depots. The results of these studies clarify the actions of both
      circulating glucocorticoids and insulin on caloric intake in adult male rats. Our
      experiments show that glucocorticoids provoke dose-related increases in total
      caloric intake that persist for days and weeks; the results also suggest that
      increasing insulin concentrations stimulated by glucocorticoids determine the
      amount of fat intake. Furthermore, we show that lard intake is associated with
      increasing insulin concentrations. Additionally, the results in adrenalectomized
      and adrenalectomized, streptozotocin-induced diabetic rats strongly suggest that
      it is a combination of corticosterone and insulin that increases abdominal fat
      depot weight. Independently of the hormonally manipulated rats, the results also
      show that intact rats voluntarily eat a considerable and stable proportion of
      their daily calories as lard when given a choice between lard and chow. These
      results suggest that some human obesities may result from elevated
      glucocorticoids and insulin increasing the proportional intake of high density
      calories.

PMID- 14962987
TI  - Development and application of a salmonid EST database and cDNA microarray: data
      mining and interspecific hybridization characteristics.
AB  - We report 80,388 ESTs from 23 Atlantic salmon (Salmo salar) cDNA libraries
      (61,819 ESTs), 6 rainbow trout (Oncorhynchus mykiss) cDNA libraries (14,544
      ESTs), 2 chinook salmon (Oncorhynchus tshawytscha) cDNA libraries (1317 ESTs), 2
      sockeye salmon (Oncorhynchus nerka) cDNA libraries (1243 ESTs), and 2 lake
      whitefish (Coregonus clupeaformis) cDNA libraries (1465 ESTs). The majority of
      these are 3' sequences, allowing discrimination between paralogs arising from a
      recent genome duplication in the salmonid lineage. Sequence assembly reveals
      28,710 different S. salar, 8981 O. mykiss, 1085 O. tshawytscha, 520 O. nerka, and
      1176 C. clupeaformis putative transcripts. We annotate the submitted portion of
      our EST database by molecular function. Higher- and lower-molecular-weight
      fractions of libraries are shown to contain distinct gene sets, and higher rates
      of gene discovery are associated with higher-molecular weight libraries. Pyloric
      caecum library group annotations indicate this organ may function in redox
      control and as a barrier against systemic uptake of xenobiotics. A microarray is
      described, containing 7356 salmonid elements representing 3557 different cDNAs.
      Analyses of cross-species hybridizations to this cDNA microarray indicate that
      this resource may be used for studies involving all salmonids.

PMID- 14962994
TI  - Paralogues of porcine aromatase cytochrome P450: a novel hydroxylase activity is
      associated with the survival of a duplicated gene.
AB  - The gonadal and placental paralogues of porcine aromatase cytochrome P450
      (P450arom) were examined for novel catalytic properties to shed light on the
      evolutionary survival of duplicated copies of an enzyme critical to reproduction.
      Recombinant gonadal P450arom catalyzed the formation of a novel metabolite from
      testosterone, identified by gas chromatography/mass spectrometry and biochemical
      analyses as 1 beta-hydroxytestosterone (1 beta OH-T), in almost equal proportion
      to 17beta-estradiol (E(2)). This activity was absent in reactions with the
      porcine placental paralogue (or other orthologues) of P450arom and was minimal
      with androstenedione. Incubations with both porcine enzymes and with bovine and
      human P450arom demonstrated that 1 beta OH-T was not aromatizable, and 1 beta OH
      T activated the androgen receptor of prostate cancer cells in vitro. Porcine
      testicular and follicular granulosa tissues synthesized 1 beta OH-T, which was
      also detected in testicular venous plasma. These results constitute the first of
      identification of a novel, perhaps potent, nonaromatizable metabolite of
      testosterone, whose synthesis (paradoxically) can be definitively ascribed to the
      activity of the gonadal paralogue of porcine P450arom. It probably represents an
      evolutionary gain of function associated with fixation and the survival of the
      genes after CYP19 duplication. Novel activities and adaptive functions may exist
      among other duplicated vertebrate aromatases.

PMID- 14962995
TI  - Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti
      related protein.
AB  - Ghrelin, a stomach-derived orexigenic hormone, has stimulated great interest as a
      potential target for obesity control. Pharmacological evidence indicates that
      ghrelin's effects on food intake are mediated by neuropeptide Y (NPY) and agouti
      related protein (AgRP) in the central nervous system. These include
      intracerebroventricular application of antibodies to neutralize NPY and AgRP, and
      the application of an NPY Y1 receptor antagonist, which blocks some of the
      orexigenic effects of ghrelin. Here we describe treatment of Agrp(-/-);Npy(-/-)
      and Mc3r(-/-);Mc4r(-/-) double knockout mice as well as Npy(-/-) and Agrp(-/-)
      single knockout mice with either ghrelin or an orally active nonpeptide ghrelin
      agonist. The data demonstrate that NPY and AgRP are required for the orexigenic
      effects of ghrelin, as well as the involvement of the melanocortin pathway in
      ghrelin signaling. Our results outline a functional interaction between the NPY
      and AgRP pathways. Although deletion of either NPY or AgRP caused only a modest
      or nondetectable effect, ablation of both ligands completely abolished the
      orexigenic action of ghrelin. Our results establish an in vivo orexigenic
      function for NPY and AgRP, mediating the effect of ghrelin.

PMID- 14962996
TI  - Reversible changes in adrenocorticotropin (ACTH)-induced adrenocortical
      steroidogenesis and expression of the peripheral-type benzodiazepine receptor
      during the ACTH-insensitive period in young rats.
AB  - We previously demonstrated decreased adrenal content of a mitochondrial
      cholesterol transporter [peripheral-type benzodiazepine receptor (PBR)] during
      the first postnatal week in rats, when ACTH-inducible steroidogenesis is low.
      Here we report that the expression of PBR protein and mRNA increases throughout
      the neonatal/juvenile period in rats in parallel with ACTH-inducible
      steroidogenesis in vitro. We also previously reported that chronic stimulation of
      rat pups with daily ACTH injections augmented the steroidogenic response of the
      developing adrenal cortex. We therefore tested the hypotheses that the change in
      phenotype induced by ACTH was permanent, and that the effects of ACTH were
      mediated by increased PBR expression. Pups were injected with ACTH or saline from
      postnatal d (pd) 2-8 or 2-14. Another group of pups received ACTH from pd 2-7,
      followed by saline from pd 8-14. On the final day, all pups were challenged with
      a test injection of ACTH or saline. Exposure to ACTH, but not saline, for 1 wk
      significantly increased adrenal mass, the corticosterone response to ACTH, and
      the expression of PBR protein and mRNA. Continued ACTH treatment for a second
      week maintained adrenal mass, steroidogenesis, and PBR mRNA expression. When ACTH
      was withdrawn after 1 wk and replaced with daily saline injections, however,
      adrenal mass, ACTH-inducible steroidogenesis, and PBR expression returned to
      levels comparable to those in age-matched saline controls (i.e. animals that had
      not received ACTH injections during the first 2 wk). Thus, although ACTH was
      capable of inducing increased steroidogenic capacity of the juvenile rat adrenal,
      its effects were only manifest when pups were exposed regularly to high plasma
      ACTH levels. ACTH, therefore, has significant, but reversible, effects on the
      development of adrenocortical function, possibly mediated in part by increased
      expression of PBR.

PMID- 14962997
TI  - Changes in glycemia by leptin administration or high- fat feeding in rodent
      models of obesity/type 2 diabetes suggest a link between resistin expression and
      control of glucose homeostasis.
AB  - Resistin is an adipose-derived hormone that has been proposed as a link among
      obesity, insulin resistance, and diabetes. In agreement with a role of resistin
      in insulin resistance, the administration of recombinant resistin led to glucose
      intolerance in mice and impaired insulin action in rat liver. However, the
      regulation of resistin expression by physiological conditions, hormones, or
      agents known to modulate insulin sensitivity does not always support the
      association between resistin and obesity-induced insulin resistance. In the
      present study we investigated the effects of leptin administration on adipose
      resistin expression in insulin-resistant and obese ob/ob mice. We show that the
      expression of resistin mRNA and protein in adipose tissue is lower in ob/ob than
      in wild-type control mice, in agreement with the reduced adipocyte resistin mRNA
      level reported in several models of obesity. Leptin administration in ob/ob mice
      resulted in improvement of insulin sensitivity concomitant with a decrease in
      resistin gene expression. The lack of effect of leptin on resistin in db/db mice
      indicated that the leptin inhibitory action on resistin expression requires the
      long leptin receptor isoform. In addition, we demonstrated that the effect of
      leptin on resistin expression was centrally mediated. High-fat feeding in
      C57BL/6J wild-type mice, which is known to induce the development of obesity and
      insulin resistance, produced an increase in resistin expression. Interestingly,
      in both ob/ob and high fat-fed mice we obtained a striking positive correlation
      between glycemia and resistin gene expression. In conclusion, our results
      demonstrate that leptin decreases resistin expression and suggest that resistin
      may influence glucose homeostasis.

PMID- 14962998
TI  - Rapid detection and differentiation of human pathogenic orthopox viruses by a
      fluorescence resonance energy transfer real-time PCR assay.
AB  - BACKGROUND: The orthopox viruses that are pathogenic for humans include variola
      major virus (VAR), monkeypox virus (MPV), cowpox virus (CPV), and to a lesser
      extent, camelpox virus (CML) and vaccinia virus (VAC). PCR is a powerful tool to
      detect and differentiate orthopox viruses, and real-time PCR has the further
      advantages of rapid turnaround time, low risk of contamination, capability of
      strain differentiation, and use of multiplexed probes. METHODS: We used real-time
      PCR with fluorescence resonance energy transfer technology to simultaneously
      detect and differentiate VAR, MPV, CPV/VAC, and CML. An internal control
      generated by cloning and mutating the PCR target gene facilitated monitoring of
      PCR inhibition in each individual test reaction. RESULTS: Strain differentiation
      results showed little interassay variability (CV, 0.4-0.6%), and the test was 100
      fold more sensitive than virus culture on Vero cells. Low copy numbers of DNA
      could be detected with > or =95% probability (235-849 genome copies/mL of
      plasma). CONCLUSIONS: The real-time PCR assay can detect and differentiate human
      pathogenic orthopox viruses. The use of an internal control qualifies the assay
      for high sample throughput, as is likely to be needed in situations of suspected
      acts of biological terrorism, e.g., use of VAR.

PMID- 14962999
TI  - Model for predicting the impact of gadolinium on plasma calcium measured by the o
      cresolphthalein method.
AB  - BACKGROUND: Gadolinium formulations, which are administered as contrast agents in
      magnetic resonance imaging examinations, interfere with colorimetric serum
      calcium determinations. METHODS: We performed an in vitro study to determine the
      extent to which three gadolinium formulations-gadodiamide (Omniscan),
      gadopentetate dimeglumine (Magnevist), and gadoversetamide (OptiMARK)-affect
      measurements by two methods that use o-cresolphthalein (Dade Behring, Inc. and
      Roche Diagnostics) and one that uses arsenazo dye (Equal Diagnostics). We also
      compared values from the o-cresolphthalein methods for 116 samples from patients
      administered gadodiamide. RESULTS: Magnevist did not affect any of the methods
      evaluated, whereas Omniscan and OptiMARK were identical in their effects. For the
      Dade method, the differences from the control sample were < or =4.0 and 7.0 mg/L
      at 0.25 and 0.5 mmol/L gadolinium, respectively. For the Roche method, the
      differences were 19, 9.0, and 5.0 mg/L at 0.5, 0.25, and 0.125 mmol/L gadolinium,
      respectively. Falsely increased calcium values were seen when samples were
      measured by the arsenazo-based method: differences were 6.0 and 3.0 mg/L at 1.0
      and 0.5 mmol/L gadolinium. Using patient data collected at our institution, we
      were able to generate a model for predicting, from a patient's glomerular
      filtration rate and the time elapsed since administration, the impact of Omniscan
      on calcium measurements by the o-cresolphthalein method from Roche Diagnostics.
      CONCLUSIONS: The predictive model can be used to calculate, in patients who have
      received gadodiamide, the minimum length of time to wait before blood collection
      to avoid pseudohypocalcemia when the Roche o-cresolphthalein method is used.

PMID- 14963000
TI  - Restoration of resting sarcomere length after uniaxial static strain is regulated
      by protein kinase Cepsilon and focal adhesion kinase.
AB  - Physiological or pathological stresses and strains produce longer or wider muscle
      cells, but resting sarcomere length remains constant. Our goal was to investigate
      the cellular mechanisms for controlling this optimal, resting sarcomere length.
      To do so, we cultured neonatal rat cardiomyocytes on microfabricated peg-and
      groove, laminin-coated silicone surfaces and applied a uniaxial static strain of
      10%. Sarcomere length was accurately measured by fast Fourier transform analysis
      of images before, within 5 minutes of, and 4 to 6 hours after imposition of the
      strain. Sarcomere length of aligned cardiomyocytes (1.94+/-0.07 microm) was
      lengthened acutely (2.06+/-0.06 microm), and recovered (1.95+/-0.07 microm) by 4
      hours. Puromycin, an mRNA translational inhibitor, prevented recovery of resting
      sarcomere length by 4 hours, thus indicating a requirement for new protein
      synthesis in the recovery process. Furthermore, activation of protein kinase
      Cepsilon (PKCepsilon) was necessary for length recovery, as nonselective PKC
      inhibitors [staurosporine (5 micromol/L) and chelerythrine chloride (10
      micromol/L)], and a replication-defective adenovirus (Adv) encoding a dominant
      negative mutant of PKCepsilon prevented the restoration of sarcomere length. To
      assess the importance of focal adhesion complexes, cardiomyocytes were infected
      with an Adv encoding a dominant-negative inhibitor of focal adhesion kinase (FAK)
      (Adv-GFP-FRNK). Adv-GFP-FRNK also prevented resting sarcomere length recovery,
      whereas a control Adv encoding only GFP did not. In conclusion, using our novel
      culture system, we provide evidence indicating that the length remodeling process
      requires new protein synthesis, PKCepsilon and FAK.

PMID- 14963001
TI  - Contribution of IKr to rate-dependent action potential dynamics in canine
      endocardium.
AB  - Previous modeling studies have suggested that the rapid component of the delayed
      rectifier (I(Kr)) may contribute importantly to action potential dynamics during
      tachycardia. To test this idea experimentally, I(Kr) was measured as the E-4031
      sensitive current in isolated canine endocardial myocytes at 37 degrees C using
      the perforated patch-clamp technique. Command potentials were trains of action
      potential waveforms recorded at cycle lengths (CLs) of 1000, 500, 320, 170, and
      120 ms. Action potential duration (APD) alternans occurred at CLs of 170 and 120
      ms. During an action potential, I(Kr) increased gradually to a maximum at -55 to 
      60 mV. Peak I(Kr) increased initially as CL was shortened from 1000 to 500 ms
      (from 0.55+/-0.03 to 0.57+/-0.03 pA/pF), but decreased progressively as CL was
      shortened further (to 0.45+/-0.03 pA/pF at CL=120 ms). Baseline I(Kr) was
      negligible at CLs of 1000 to 320 ms, but increased to 0.12+/-0.01 pA/pF at a CL
      of 120 ms. During APD alternans, peak I(Kr) was larger for the short than for the
      long action potential (0.48+/-0.03 versus 0.46+/-0.03 pA/pF). A computer model of
      I(Kr) based on these data indicated that increasing I(Kr) suppressed alternans
      and decreasing I(Kr) increased alternans. In support of the latter result,
      inhibition of I(Kr) by E-4031 increased the maximal amplitude of alternans. These
      results indicate that I(Kr) contributes importantly to rate-related alterations
      of repolarization, including APD alternans. Modifying I(Kr) may be a promising
      approach to suppressing alternans and thereby preventing ventricular
      tachyarrhythmias.

PMID- 14963002
TI  - Phosphatidylinositol 3-kinase/Akt regulates angiotensin II-induced inhibition of
      apoptosis in microvascular endothelial cells by governing survivin expression and
      suppression of caspase-3 activity.
AB  - Angiotensin II (Ang II) plays essential roles in vascular homeostasis, neointimal
      formation, and postinfarct remodeling. Although Ang II has been shown to regulate
      apoptosis in cardiomyocytes and vascular smooth muscle cells, its role in
      vascular endothelial cells (ECs) remains elusive. To address this issue, we first
      performed TUNEL and caspase-3 activity assays with porcine microvascular ECs
      challenged by serum deprivation. Ang II significantly reduced the ratio of
      apoptotic cells and caspase-3 activity. The Ang II type 1 receptor (AT1) was
      responsible for these effects. Among the signaling molecules downstream of AT1,
      we revealed that PI3-kinase/Akt pathway plays a predominant role in the
      antiapoptotic effect of Ang II. Interestingly, the expression of survivin, a
      central molecule of cell survival, increased after Ang II stimulation.
      Overexpression of a dominant-negative form of Akt abolished both Ang II-induced
      antiapoptosis and survivin protein expression. In a murine model of hyperoxygen
      induced retinal vascular regression, AT1a knockout mice showed a significant
      increase in retinal avascular areas. Our data indicate that Ang II plays a
      critical antiapoptotic role in vascular ECs by a mechanism involving PI3
      kinase/Akt activation, subsequent upregulation of survivin, and suppression of
      caspase-3 activity.

PMID- 14963003
TI  - Antioxidants inhibit nuclear export of telomerase reverse transcriptase and delay
      replicative senescence of endothelial cells.
AB  - Aging is associated with a rise in intracellular reactive oxygen species (ROS)
      and a loss of telomerase reverse transcriptase activity. Incubation with H2O2
      induced the nuclear export of telomerase reverse transcriptase (TERT) into the
      cytosol in a Src-family kinase-dependent manner. Therefore, we investigated the
      hypothesis that age-related increase in reactive oxygen species (ROS) may induce
      the nuclear export of TERT and contribute to endothelial cell senescence.
      Continuous cultivation of endothelial cells resulted in an increased endogenous
      formation of ROS starting after 29 population doublings (PDL). This increase was
      accompanied by mitochondrial DNA damage and preceded the onset of replicative
      senescence at PDL 37. Along with the enhanced formation of ROS, we detected an
      export of nuclear TERT protein from the nucleus into the cytoplasm and an
      activation of the Src-kinase. Moreover, the induction of premature senescence by
      low concentrations of H2O2 was completely blocked with the Src-family kinase
      inhibitor PP2, suggesting a crucial role for Src-family kinases in the induction
      of endothelial cell aging. Incubation with the antioxidant N-acetylcysteine, from
      PDL 26, reduced the intracellular ROS formation and prevented mitochondrial DNA
      damage. Likewise, nuclear export of TERT protein, loss in the overall TERT
      activity, and the onset of replicative senescence were delayed by incubation with
      N-acetylcysteine. Low doses of the statin, atorvastatin (0.1 micromol/L), had
      also effects similar to those of N-acetylcysteine. We conclude that both
      antioxidants and statins can delay the onset of replicative senescence by
      counteracting the increased ROS production linked to aging of endothelial cells.

PMID- 14963004
TI  - Neointimal smooth muscle cells display a proinflammatory phenotype resulting in
      increased leukocyte recruitment mediated by P-selectin and chemokines.
AB  - Leukocyte recruitment is crucial for the response to vascular injury in
      spontaneous and accelerated atherosclerosis. Whereas the mechanisms of leukocyte
      adhesion to endothelium or matrix-bound platelets have been characterized, less
      is known about the proadhesive role of smooth muscle cells (SMCs) exposed after
      endothelial denudation. In laminar flow assays, neointimal rat SMCs (niSMCs)
      supported a 2.5-fold higher arrest of monocytes and "memory" T lymphocytes than
      medial SMCs, which was dependent on both P-selectin and VLA-4, as demonstrated by
      blocking antibodies. The increase in monocyte arrest on niSMCs was triggered by
      the CXC chemokine GRO-alpha and fractalkine, whereas "memory" T cell arrest was
      mediated by stromal cell-derived factor (SDF)-1alpha. This functional phenotype
      was paralleled by a constitutively increased mRNA and surface expression of P
      selectin and of relevant chemokines in niSMCs, as assessed by real-time PCR and
      flow cytometry. The increased expression of P-selectin in niSMCs versus medial
      SMCs was associated with enhanced NF-kappaB activity, as revealed by
      immunofluorescence staining for nuclear p65 in vitro. Inhibition of NF-kappaB by
      adenoviral IkappaBalpha in niSMCs resulted in a marked reduction of increased
      leukocyte arrest in flow. Furthermore, P-selectin expression by niSMCs in vivo
      was confirmed in a hypercholesterolemic mouse model of vascular injury by double
      immunofluorescence and by RT-PCR after laser microdissection. In conclusion, we
      have identified a NF-kappaB-mediated proinflammatory phenotype of niSMCs that is
      characterized by increased P-selectin and chemokine expression and thereby
      effectively supports leukocyte recruitment.

PMID- 14963005
TI  - Functional basis of sinus bradycardia in congenital heart block.
AB  - Congenital heart block (CHB) is a conduction abnormality characterized by
      complete atrioventricular (AV) block. CHB affects fetuses and/or newborn of
      mothers with autoantibodies reactive with ribonucleoproteins 48-kDa SSB/La, 52
      kDa SSA/Ro, and 60-kDa SSA/Ro. We recently established animal models of CHB and
      reported, for the first time, significant sinus bradycardia preceding AV block.
      This unexpected observation implies that the spectrum of conduction abnormalities
      extends beyond the AV node to also affect the SA node. To test this hypothesis,
      we investigated the functional basis of this sinus bradycardia by characterizing
      the effects of antibodies from mothers with CHB children (positive IgG) on ionic
      currents that are known to significantly contribute to spontaneous pacing in SA
      node cells. We recorded L- (I(Ca.L)) and T- (I(Ca.T)) type Ca2+, delayed
      rectifier K+ (I(K)), hyperpolarization-activated (I(f)) currents, and action
      potentials (APs) from young rabbit SA node cells. We demonstrated that positive
      IgG significantly inhibited both I(Ca.T) and I(Ca.L) and induced sinus
      bradycardia but did not affect I(f) and I(K). Normal IgG from mothers with
      healthy children did not affect all the currents studied and APs. These results
      establish that IgG from mothers with CHB children causes substantial inhibition
      of I(Ca.T) and I(Ca.L), two important pacemaker currents in rabbit SA node cells
      and point to both I(Ca.T) and I(Ca.L) as major players in the ionic mechanism by
      which maternal antibodies induce sinus bradycardia in CHB. These novel findings
      have important clinical significance and suggest that sinus bradycardia may be a
      potential marker in the detection and prevention of CHB. The full text of this
      article is available online at http://circres.ahajournals.org

PMID- 14963006
TI  - Prostacyclin induces apoptosis of vascular smooth muscle cells by a cAMP-mediated
      inhibition of extracellular signal-regulated kinase activity and can counteract
      the mitogenic activity of endothelin-1 or basic fibroblast growth factor.
AB  - Prostanoids can suppress vascular smooth muscle cell (VSMC) proliferation, but
      the mechanism through which this is mediated has not been identified. In this
      study, we show rat aortic VSMCs to express the EP1, EP2, EP3, EP4, and IP
      receptors. The EP4 receptor-specific agonist, 11-deoxy-PGE1, induced a time
      dependent phosphorylation of protein kinase C and extracellular signal-regulated
      kinase (ERK) 1/2 in serum-depleted (0.1%) VSMCs, whereas the EP2 receptor
      agonist, butaprost, was without effect. PGI2 or iloprost at the IP receptor
      inhibited basal ERK phosphorylation with IC50 values of 10 nmol/L. Iloprost also
      attenuated the sustained activation of ERK induced by endothelin-1 or basic
      fibroblast growth factor (bFGF). Endothelin-1 or bFGF significantly increased the
      number of VSMCs counted 24 hours later compared with basal, and both responses
      were blocked by the MEK inhibitor, U0126, or iloprost. Under basal conditions,
      U0126 or iloprost reduced the number of viable cells and increased caspase-3
      activity, which could be reversed by coapplication with endothelin-1, bFGF, or
      the adenylate cyclase inhibitor, SQ22536. Endothelin-1, bFGF, or SQ22536
      prevented the depression to below basal levels of ERK phosphorylation induced by
      iloprost. Forskolin activated caspase-3 and attenuated basal ERK phosphorylation,
      which were prevented by SQ22536, endothelin-1, or bFGF. These data suggest that
      iloprost induces apoptosis via a cAMP-mediated suppression of ERK activity. In
      turn, this apoptotic response can be blocked by a mitogenic stimulus that re
      establishes ERK activity back to basal levels, but at the expense of any
      concomitant proliferative activity. However, ERK stimulation by a selective EP4
      receptor agonist, suggests that prostanoids may have diverse and complex roles in
      VSMC physiology.

PMID- 14963007
TI  - Collateral artery growth (arteriogenesis) after experimental arterial occlusion
      is impaired in mice lacking CC-chemokine receptor-2.
AB  - Arteriogenesis has been associated with the presence of monocytes/macrophages
      within the collateral vessel wall. Induced macrophage migration in vivo is driven
      by the binding of monocyte chemoattractant protein-1 (MCP-1, or CCL2 in the new
      nomenclature) to the CCR2-chemokine receptor on macrophages. To determine whether
      the CCL2-CCR2 signaling pathway is involved in the accumulation of macrophages in
      growing collateral vessels, we used mice that are deficient in CCR2 in a model of
      experimental arterial occlusion and collateral vessel growth. In an in vitro CCL2
      driven chemotaxis assay, mononuclear cells isolated from wild-type BALB/c mice
      exhibited CCL2 concentration-dependent migration, whereas this migration was
      abolished in cells from CCR2(-/-) mice on a BALB/c genetic background. In vivo,
      blood flow recovery as measured by laser Doppler (LDI) and MRI (MRI) was impaired
      in CCR2(-/-) mice on either the BALB/c or C57BL/6 genetic backgrounds. Three
      weeks after femoral artery ligation, LDI perfusion ratio of operated versus
      nonoperated distal hindlimb in BALB/c wild-type mice increased to 0.45+/-0.06 and
      in CCR2(-/-) animals only to 0.21+/-0.03 (P<0.01). In C57BL/6 mice, ratio
      increased to 0.96+/-0.09 and 0.85+/-0.08 (P<0.05), respectively. MRI at 3 weeks
      (0.76+/-0.06 versus 0.62+/-0.01; P<0.05) and hemoglobin oxygen saturation
      measurements confirmed these findings. Active foot movement score significantly
      decreased and gastrocnemius muscle atrophy was significantly greater in CCR2(-/-)
      mice. Morphometric analysis showed a lesser increase in collateral vessel
      diameters in CCR2(-/-) mice. Importantly, the number of invaded
      monocytes/macrophages in the perivascular space of collateral arteries of CCR2(-/
      ) animals was dramatically reduced in comparison to wild-type mice. In
      conclusion, our results demonstrate that the CCR2 signaling pathway is essential
      for efficient collateral artery growth.

PMID- 14963008
TI  - Platelet-derived growth factor-AB promotes the generation of adult bone marrow
      derived cardiac myocytes.
AB  - The directed generation of cardiac myocytes from endogenous stem cells offers the
      potential for novel therapies for cardiovascular disease. To facilitate the
      development of such approaches, we sought to identify and exploit the pathways
      directing the generation of cardiac myocytes from adult rodent bone marrow cells
      (BMCs). In vitro cultures supporting the spontaneous generation of functional
      cardiac myocytes from murine BMCs demonstrated induced expression of platelet
      derived growth factor (PDGF)-A and -B isoforms with alpha- and beta-myosin heavy
      chains as well as connexin43. Supplementation of PDGF-AB speeded the kinetics of
      myocyte development in culture by 2-fold. In a rat heart, myocardial infarction
      pretreatment model PDGF-AB also promoted the derivation of cardiac myocytes from
      BMCs, resulting in a significantly greater number of islands of cardiac myocyte
      bundles within the myocardial infarction scar compared with other treatment
      groups. However, gap junctions were detected only between the cardiac myocytes
      receiving BMCs alone, but not BMCs injected with PDGF-AB. Echocardiography and
      exercise testing revealed that the functional improvement of hearts treated with
      the combination of BMCs and PDGF-AB was no greater than with injections of BMCs
      or PDGF-AB alone. These studies demonstrated that PDGF-AB enhances the generation
      of BMC-derived cardiac myocytes in rodent hearts, but suggest that alterations in
      cellular patterning may limit the functional benefit from the combined injection
      of PDGF-AB and BMCs. Strategies based on the synergistic interactions of PDGF-AB
      and endogenous stem cells will need to maintain cellular patterning in order to
      promote the restoration of cardiac function after acute coronary occlusion.

PMID- 14963009
TI  - Thromboxane A2 receptor agonists antagonize the proangiogenic effects of
      fibroblast growth factor-2: role of receptor internalization, thrombospondin-1,
      and alpha(v)beta3.
AB  - Thromboxane (TX) A2 is released from multiple cell types and is a prime mediator
      of the pathogenesis of many vascular events, including angiogenesis. Endothelial
      cells express TXA2 receptors (TP) but the effects of TP stimulation on
      angiogenesis remain controversial. In this study, we show that stimulation of
      endothelial cell TP impairs ligand-induced FGF receptor internalization and
      consequently abrogates FGF-2-induced endothelial cell migration in vitro and
      angiogenesis in vivo. Prevention of FGF-2-induced angiogenesis was associated
      with expression of the TPbeta isoform. The deficit in FGFR1 internalization was
      mediated through activation of TPbeta preventing the FGF-2-mediated decrease in
      p53 expression, thus enhancing thrombospondin-1 (TSP-1) release from EC and
      reducing FGFR1 internalization. Once released TSP-1 interacted with the
      alpha(v)beta3 integrin on the EC surface. On stimulation, FGFR1 and alpha(v)beta3
      were found to associate in a complex. We determined that complex formation was
      important for receptor internalization as conditions that inhibit FGFR1
      internalization, such as inappropriate ligation of alpha(v)beta3 by either TSP-1
      or a neutralizing antibody, disrupted the complex. These results establish a
      novel role for isoform specific regulation of angiogenesis by TP, provide the
      first functional significance for the existence of two TP isoforms in humans, and
      clarify the mechanism by which TP signaling regulates FGFR1 kinetics and
      signaling.

PMID- 14963010
TI  - Vasorelaxation by red blood cells and impairment in diabetes: reduced nitric
      oxide and oxygen delivery by glycated hemoglobin.
AB  - Vascular dysfunction in diabetes is attributed to lack of bioavailable nitric
      oxide (NO) and is postulated as a primary cause of small vessel complications as
      a result of poor glycemic control. Although it has been proposed that NO is bound
      by red blood cells (RBCs) and can induce relaxation of blood vessels distal to
      its site of production in the normal circulation, the effect of RBC glycation on
      NO binding and relaxation of hypoxic vessels is unknown. We confirm RBC-induced
      vessel relaxation is inversely related to tissue oxygenation and is proportional
      to RBC S-nitrosohemoglobin (HbSNO) content (but not nitrosylhemoglobin content).
      We show more total NO bound inside highly glycated RBCs (0.0134 versus 0.0119
      NO/Hb, respectively; P<0.05) although proportionally less HbSNO (0.0053 versus
      0.0088 NO/Hb, respectively; P<0.05). We also show glycosylation impairs the
      vasodilator function of RBCs within a physiological range of tissue oxygenation.
      These findings may represent an important contribution to reduced NO
      bioavailability in the microvasculature in diabetes.

PMID- 14963011
TI  - Rhythmic ryanodine receptor Ca2+ releases during diastolic depolarization of
      sinoatrial pacemaker cells do not require membrane depolarization.
AB  - Localized, subsarcolemmal Ca2+ release (LCR) via ryanodine receptors (RyRs)
      during diastolic depolarization of sinoatrial nodal cells augments the terminal
      depolarization rate. We determined whether LCRs in rabbit sinoatrial nodal cells
      require the concurrent membrane depolarization, or are intrinsically rhythmic,
      and whether rhythmicity is linked to the spontaneous cycle length. Confocal
      linescan images revealed persistent LCRs both in saponin-permeabilized cells and
      in spontaneously beating cells acutely voltage-clamped at the maximum diastolic
      potential. During the initial stage of voltage clamp, the LCR spatiotemporal
      characteristics did not differ from those in spontaneously beating cells, or in
      permeabilized cells bathed in 150 nmol/L Ca2+. The period of persistent rhythmic
      LCRs during voltage clamp was slightly less than the spontaneous cycle length
      before voltage clamp. In spontaneously beating cells, in both transient and
      steady states, LCR period was highly correlated with the spontaneous cycle
      length; and regardless of the cycle length, LCRs occurred predominantly at a
      constant time, ie, 80% to 90% of the cycle length. Numerical model simulations
      incorporating LCRs reproduce the experimental results. We conclude that diastolic
      LCRs reflect rhythmic intracellular Ca2+ cycling that does not require the
      concomitant membrane depolarization, and that LCR periodicity is closely linked
      to the spontaneous cycle length. Thus, the biological clock of sinoatrial nodal
      pacemaker cells, like that of many other rhythmic functions occurring throughout
      nature, involves an intracellular Ca2+ rhythm.

PMID- 14963012
TI  - Theaflavin-3,3'-digallate and penta-O-galloyl-beta-D-glucose inhibit rat liver
      microsomal 5alpha-reductase activity and the expression of androgen receptor in
      LNCaP prostate cancer cells.
AB  - Androgens play a critical role in regulating the growth, differentiation and
      survival of epithelial cells in many androgen-responsive organs, such as prostate
      and skin. The enzyme steroid 5alpha-reductase (EC 1.3.99.5) catalyzes the
      conversion of testosterone (T) to a more active androgen, dihydrotestosterone
      (DHT). DHT then binds to androgen receptors (AR) and functions in the nucleus to
      regulate specific gene expression. Androgens via their cognate receptor may be
      involved in the development and progression of benign prostate hyperplasia,
      prostate cancer, hirsutism, male pattern alopecia and acne. The aim of this study
      was to determine whether theaflavin-3,3'-digallate (TF3) and penta-O-galloyl-beta
      D-glucose (5GG) have inhibitory effects on androgen production and action. We
      found that TF3 and 5GG inhibit rat liver microsomal 5alpha-reductase activity.
      Furthermore, TF3 and 5GG significantly reduced androgen-responsive LNCaP prostate
      cancer cell growth, suppressed expression of the AR and lowered androgen-induced
      prostate-specific antigen secretion and fatty acid synthase protein level. In
      conclusion, our result suggests that TF3 and 5GG might be useful chemoprevention
      agents for prostate cancer through suppressing the function of androgen and its
      receptor.

PMID- 14963013
TI  - Discrimination of genotoxic from non-genotoxic carcinogens by gene expression
      profiling.
AB  - Two general mechanisms are implicated in chemical carcinogenesis. The first
      involves direct damage to DNA, referred to as genotoxic (GTX), to which the cell
      responds by repair of the damages, arrest of the cell cycle or induction of
      apoptosis. The second is non-DNA damaging, non-genotoxic (NGTX), in which a wide
      variety of cellular processes may be involved. Therefore, it can be hypothesized
      that modulation of the underlying gene expression patterns is profoundly distinct
      between GTX and NGTX carcinogens, and thus that expression profiling is
      applicable for classification of chemical carcinogens as GTX or NGTX. We
      investigated this hypothesis by analysing modulation of gene expression profiles
      induced by 20 chemical carcinogens in HepG2 cells with application of cDNA
      microarrays that contain 597 toxicologically relevant genes. In total, 22
      treatments were included, divided in two sets. The training set consisted of 16
      treatments (nine genotoxins and seven non-genotoxins) and the validation set of
      six treatments (three and three). Class discrimination models based on Pearson
      correlation analyses for the 20 most discriminating genes were developed with
      data from the training set, where after the models were tested with all data.
      Using all data, the correctness for classification of the carcinogens from the
      training set was clearly better than that for the validation set, namely 81 and
      33%, respectively. Exclusion of the treatments that had only marginal effects on
      the expression profiles, improved the discrimination for the training and
      validation sets to 92 and 100% correctness, respectively. Exclusion of the gene
      expression signals that were hardly altered also improved classification, namely
      to 94 and 80%. Therefore, our study proves the principle that gene expression
      profiling can discriminate carcinogens with major differences in their mode of
      actions, namely genotoxins versus non-genotoxins.

PMID- 14963014
TI  - Tumor growth suppression by alpha-eleostearic acid, a linolenic acid isomer with
      a conjugated triene system, via lipid peroxidation.
AB  - We have previously shown that conjugated linolenic acids (CLnA) prepared by
      alkaline isomerization have a stronger antitumor effect than conjugated linoleic
      acids (CLA). In this study we have compared the suppressive effect on tumor
      growth of alpha-eleostearic acid (alpha-ESA, 9Z11E13E-18:3) with those of the CLA
      isomers 9Z11E-CLA and 10E12Z-CLA, using nude mice into which DLD-1 human colon
      cancer cells were transplanted. The results showed that alpha-ESA, which is a
      CLnA that can be prepared from natural sources in bulk, had a stronger antitumor
      effect than CLA. DNA fragmentation was enhanced and lipid peroxidation was
      increased in tumor tissues of the alpha-ESA-fed mice, which suggested that alpha
      ESA induced apoptosis via lipid peroxidation. Furthermore, treatment of DLD-1
      cells with alpha-ESA, 9Z11E-CLA and 10E12Z-CLA confirmed that alpha-ESA had a
      stronger antitumor effect than CLA in cultured cell lines. The induction of
      apoptosis by alpha-ESA was consistent with enhanced DNA fragmentation, increased
      caspase activity and increased expression of caspase mRNA following alpha-ESA
      treatment. Addition of alpha-tocopherol, an antioxidant, suppressed oxidative
      stress and apoptosis, suggesting that these effects were associated with lipid
      peroxidation.

PMID- 14963015
TI  - Cyclooxygenase-2 inhibitors suppress the growth of human hepatocellular carcinoma
      implants in nude mice.
AB  - Cyclooxygenase (COX)-2 is expressed in hepatocellular carcinomas (HCCs) and HCC
      cell lines. COX-2 inhibition strongly suppresses growth of HCC cells in vitro by
      inducing apoptosis and reducing proliferation. Here, we evaluate the in vivo
      effects and mechanism of COX-2 inhibition of human HCC cell line derived
      xenotransplanted tumors in nude mice. Firstly, nude mice were treated with a COX
      2 specific inhibitor (meloxicam) or a non-specific inhibitor (sulindac) starting
      5 days prior to tumor cell injection. After 35 days mice were killed and tumors
      were analyzed morphologically and assayed for proliferation (Ki67), apoptosis
      (M30) and COX-2 expression. Secondly, mice were treated with meloxicam or
      sulindac after tumors had reached a diameter of at least 0.2 cm. COX-2 expression
      was maintained in implant tumors at levels comparable with parental cells.
      Selective COX-2 inhibition led to a significant reduction of tumor growth and
      weight. COX-2 inhibition had a significant anti-proliferative and pro-apoptotic
      effect on tumor cells. These results demonstrate that under experimental
      conditions selective COX-2 inhibition suppresses solid HCC growth in vivo and,
      therefore may have preventive and therapeutic potential for human HCCs.

PMID- 14963016
TI  - Reduced MGMT activity in human colorectal adenomas is associated with K-ras GC
      >AT transition mutations in a population exposed to methylating agents.
AB  - There is increasing evidence to suggest that O(6)-alkyl guanine DNA
      alkyltransferase (MGMT) activity provides protection against alkylating agent
      induced formation of GC-->AT transition mutations in the K-ras oncogene of
      colorectal tumours. As this mutagenic event occurs during the growth of adenomas,
      both biomarkers of exposure (N7-methylguanine levels in DNA) and susceptibility
      (MGMT activity) were measured in biopsy samples obtained from normal and
      adenomatous tissue from 34 patients with large adenomas (>10 mm in size). There
      was no correlation between MGMT activity in the adenoma and in matched normal
      tissue. However, MGMT activity was significantly lower in adenoma tissue than in
      adjacent normal mucosa (5.18 versus 7.05 fmol/microg DNA, P = 0.01), particularly
      in men and those whose age was greater than the median. Upon stratification by K
      ras mutational status, MGMT activity was lower in adenomas bearing a K-ras GC-
      >AT transition mutation (mean 4.21 fmol/microg DNA) than in adjacent normal
      tissue (mean 7.7 fmol/microg DNA; P < 0.004). In contrast, there was no
      significant difference in MGMT activity in adenomas lacking a K-ras GC-->AT
      transition mutation and adjacent normal mucosa. N7-methylguanine levels however
      did not vary with age, gender, K-ras mutational status or MGMT activity. These
      results are consistent with the acquisition of K-ras GC-->AT transition mutations
      in adenomas with low MGMT activity as a result of unavoidable exposure to
      methylating agents.

PMID- 14963017
TI  - The bioenergetic signature of lung adenocarcinomas is a molecular marker of
      cancer diagnosis and prognosis.
AB  - The aim of this study was to investigate the mitochondrial bioenergetic signature
      of lung adenocarcinomas as a prognostic marker of cancer progression. For this
      purpose, a series of 90 lung adenocarcinomas and 10 uninvolved lung samples were
      examined for quantitative differences in protein expression using two-dimensional
      polyacrylamide gel electrophoresis. The beta subunit of the mitochondrial H(+)
      ATP synthase (beta-F1-ATPase) and heat shock protein 60 (Hsp 60), and the
      glycolytic glyceraldehyde-3-phosphate dehydrogenase (GAPDH), used to define the
      bioenergetic cellular (BEC) index, were identified using mass spectrometry and
      specific antibodies. Correlations of the expression level of the protein markers
      and of the BEC index were established with the clinicopathological information of
      the tumors and the follow-up data of the patients. The expression of beta-F1
      ATPase is significantly reduced in lung adenocarcinomas in the absence of
      significant changes in the expression of Hsp 60 and of a major GAPDH isoform.
      Cross-validation analysis using the beta-F1-ATPase/Hsp 60 ratio and GAPDH
      expression as predictor variables revealed a classification sensitivity of 97.3%.
      The beta-F1-ATPase/Hsp 60 ratio is significantly higher in well differentiated
      and bronchioloalveolar tumors than in moderate or poorly differentiated and in
      bronchial-derived tumors. The BEC index of T1 tumors was significantly higher
      than that of T2 tumors. Likewise, stage IA tumors had a higher BEC index than
      stage IB tumors. Kaplan-Meier survival analysis using the BEC index as predictor
      of survival revealed that within tumors of the same size or stage I or with no
      lymph node metastasis (N0) the patients bearing 'low' BEC index tumors had a
      significant worse prognosis. We conclude that the bioenergetic signature of lung
      adenocarcinomas is altered, further providing a relevant marker for the diagnosis
      and classification of lung adenocarcinomas, and for the prognosis of lung cancer
      patients.

PMID- 14963018
TI  - Evidence of STAT1 phosphorylation modulated by MAPKs, MEK1 and MSK1.
AB  - Phosphorylation at Ser727 in signal transducer and activator of transcription 1
      (STAT1) is essential for its activation and signal transduction. However, the
      upstream kinases responsible for phosphorylating Ser727 are still elusive. Here,
      we provide evidence showing that UVA-induced mitogen-activated protein kinase
      (MAPK) signaling pathways lead to STAT1 Ser727 phosphorylation. Our experimental
      results show that UVA-induced Ser727 phosphorylation of STAT1 was, to different
      degrees, diminished by PD98059 and U0126, two specific inhibitors of MEKs, and
      SB202190 and PD169316, inhibitors of p38 kinase and c-Jun N-terminal kinases
      (JNKs), respectively. STAT1 phosphorylation was also blocked by a dominant
      negative mutant of p38beta kinase or JNK1, JNK1- or JNK2-deficiency, or an N
      terminal or C-terminal kinase-dead mutant of mitogen- and stress-activated
      protein kinase 1 (MSK1), a downstream kinase closer to p38 kinase and
      extracellular signal-regulated kinases (ERKs). In vitro kinase assays using the
      combined STAT1 proteins as substrates from immunoprecipitation and glutathione S
      transferase pull down show that active ERK1, JNK1, p38 kinase, MEK1 and MSK1
      stimulated phosphorylation of STAT1 (Ser727) indirectly through an unidentified
      factor or a downstream kinase. Overall, our data indicate that phosphorylation of
      STAT1 at Ser727 occurs through diverse MAPK cascades including MEK1, ERKs, p38
      kinase, JNKs and MSK1 in the cellular response to UVA.

PMID- 14963020
TI  - Zena Werb [interview by Fiona M Watt].

PMID- 14963021
TI  - Tracking down lipid flippases and their biological functions.
AB  - The various organellar membranes of eukaryotic cells display striking differences
      in the composition, leaflet distribution and transbilayer movement of their
      lipids. In membranes such as the endoplasmic reticulum, phospholipids can move
      readily across the bilayer, aided by membrane proteins that facilitate a passive
      equilibration of lipids between both membrane halves. In the plasma membrane, and
      probably also in the late Golgi and endosomal compartments, flip-flop of
      phospholipids is constrained and subject to a dynamic, ATP-dependent regulation
      that involves members of distinct protein families. Recent studies in yeast,
      parasites such as Leishmania, and mammalian cells have identified several
      candidates for lipid flippases, and whereas some of these serve a fundamental
      role in the release of lipids from cells, others appear to have unexpected and
      important functions in vesicular traffic: their activities are required to
      support vesicle formation in the secretory and endocytic pathways.

PMID- 14963022
TI  - Poly(ADP-ribosyl)ated chromatin domains: access granted.
AB  - The seemingly static architecture of interphase and mitotic chromatin betrays an
      otherwise elegantly dynamic entity capable of remodelling itself to facilitate
      DNA replication, transcription, repair and recombination. Remodelling of local
      chromatin domains in response to physiological cues proceeds, at least in part,
      through transient cycles of relaxation and condensation that require use of
      histone variants and post-translational modifications of histones. Studies have
      connected poly(ADP-ribosyl)ation of histones with virtually every aspect of DNA
      metabolism and function over the years, most notably with the response to DNA
      damage, where convincing evidence supports its essential role granting repair
      machinery access to damaged DNA. Recent reports extend this notion to
      transcription and the maintenance of genomic stability, thereby supporting a
      general role for nuclear poly(ADP-ribosyl)ation in many aspects of genomic
      activity. The phenomenon might contribute to the 'histone code' by dictating
      levels of local chromatin compaction.

PMID- 14963023
TI  - A non-chromosomal factor allows viability of Schizosaccharomyces pombe lacking
      the essential chaperone calnexin.
AB  - Calnexin is a molecular chaperone playing key roles in protein folding and the
      quality control of this process in the endoplasmic reticulum. We, and others,
      have previously demonstrated that cnx1(+), the gene encoding the calnexin
      homologue in Schizosaccharomyces pombe, is essential for viability. We show that
      a particular cnx1 mutant induces a novel mechanism allowing the survival of S.
      pombe cells in the absence of calnexin/Cnx1p. Calnexin independence is dominant
      in diploid cells and is inherited in a non-Mendelian manner. Remarkably, this
      survival pathway, bypassing the necessity for calnexin, can be transmitted by
      transformation of cell extracts into a wild-type naive strain, thus implicating a
      non-chromosomal factor. Nuclease and UV treatments of cells extracts did not
      obliterate transmission of calnexin independence by transformation. However,
      protease digestion of extracts did reduce the appearance of calnexin-independent
      cells, indicating that a protein element is required for calnexin-less viability.
      We discuss a model in which this calnexin-less survival mechanism would be
      activated and perpetuated by a protein component acting as a genetic element.

PMID- 14963024
TI  - Human T-cell lymphotropic virus type 1 tax induction of biologically Active NF
      kappaB requires IkappaB kinase-1-mediated phosphorylation of RelA/p65.
AB  - Activation of the NF-kappaB/Rel family of transcription factors proceeds through
      a catalytic complex containing IkappaB kinase (IKK)-1 and IKK2. Targeted
      disruption of each of the IKK genes suggests that these two kinases may mediate
      distinct functions in the activation pathway. In our studies of the human T-cell
      lymphotropic virus type 1 (HTLV-1) Tax oncoprotein, we have uncovered a new
      function of IKK1 required for complete activation of the NF-kappaB
      transcriptional program. In IKK1(-/-) murine embryonic fibroblasts (MEFs), Tax
      normally induced early NF-kappaB activation events. However, NF-kappaB induced by
      Tax in these IKK1(-/-) cells was functionally impaired. In IKK1(-/-) (but not
      wild-type) MEFs, Tax failed to activate several different kappaB reporter
      constructs or to induce the endogenous IkappaBalpha gene. In contrast, Tax
      normally activated the cAMP-responsive element-binding protein/activating
      transcription factor pathway, leading to full stimulation of an HTLV-1 long
      terminal repeat reporter construct in IKK1(-/-) cells. Furthermore,
      reconstitution of IKK1(-/-) cells with kinase-proficient (but not kinase
      deficient) forms of IKK1 restored the Tax induction of full NF-kappaB
      transactivation. We further found that the defect in NF-kappaB action in IKK1(-/
      ) cells correlated with a failure of Tax to induce phosphorylation of the
      RelA/p65 subunit of NF-kappaB at Ser(529) and Ser(536). Such phosphorylation of
      RelA/p65 was readily detected in wild-type MEFs. Phosphorylation of Ser(536) was
      required for a complete response to Tax expression, whereas phosphorylation of
      Ser(529) appeared to be less critical. Together, these findings highlight
      distinct roles for the IKK1 and IKK2 kinases in the activation of NF-kappaB in
      response to HTLV-1 Tax. IKK2 plays a dominant role in signaling for IkappaBalpha
      degradation, whereas IKK1 appears to play an important role in enhancing the
      transcriptional activity of NF-kappaB by promoting RelA/p65 phosphorylation.

PMID- 14963025
TI  - A molecular understanding of mitoxantrone-DNA adduct formation: effect of
      cytosine methylation and flanking sequences.
AB  - When mitoxantrone is activated by formaldehyde it can form adducts with DNA.
      These occur preferentially at CpG and CpA sequences and are enhanced 2-3-fold at
      methylated CpG sequences compared with non-methylated sites. We sought to
      understand the molecular factors involved in enhanced adduct formation at these
      methylated sites. This required, first, clarification of factors that contributed
      to the formation of adducts at CpG sites. For this purpose mass spectrometry of
      an oligonucleotide duplex (containing a single CpG adduct site) was used to
      confirm the presence of an additional carbon atom (derived from formaldehyde) on
      the drug-DNA complex. The effect of 3'-flanking sequences was revealed by
      electrophoretic analysis of oligonucleotide-drug adducts, and the preferred
      adduct-forming site was identified as 5'-CGG-3'. Radiolabeled studies of drug-DNA
      adducts confirmed that the site of attachment involved the exocyclic amino of
      guanine. Molecular modeling analysis of the relative stability of the
      intercalated form of mitoxantrone was consistent with observed adduct-forming
      potential of CG sites with varying flanking sequences. The known preference for
      adduct formation at methylated CG sites was confirmed by energetics calculations
      and shown to be due to a shift of equilibrium of the intercalated form of the
      drug from the major groove (at CG sites) to the minor groove (at methylated CG
      sites). This increases the relative amount of drug that is located adjacent to
      the N-2 exocyclic amino of guanine in the minor groove, where covalent linkage is
      facilitated. These results account for the enhanced covalent binding of
      mitoxantrone to methylated CG sequences and provide a molecular model of the
      interactions.

PMID- 14963026
TI  - Targeted mutation of the MLN64 START domain causes only modest alterations in
      cellular sterol metabolism.
AB  - The StAR-related lipid transfer (START) domain, first identified in the
      steroidogenic acute regulatory protein (StAR), is involved in the intracellular
      trafficking of lipids. Sixteen mammalian START domain-containing proteins have
      been identified to date. StAR, a protein targeted to mitochondria, stimulates the
      movement of cholesterol from the outer to the inner mitochondrial membranes,
      where it is metabolized into pregnenolone in steroidogenic cells. MLN64, the
      START domain protein most closely related to StAR, is localized to late endosomes
      along with other proteins involved in sterol trafficking, including NPC1 and
      NPC2, where it has been postulated to participate in sterol distribution to
      intracellular membranes. To investigate the role of MLN64 in sterol metabolism,
      we created mice with a targeted mutation in the Mln64 START domain, expecting to
      find a phenotype similar to that in humans and mice lacking NPC1 or NPC2
      (progressive neurodegenerative symptoms, free cholesterol accumulation in
      lysosomes). Unexpectedly, mice homozygous for the Mln64 mutant allele were
      viable, neurologically intact, and fertile. No significant alterations in plasma
      lipid levels, liver lipid content and distribution, and expression of genes
      involved in sterol metabolism were observed, except for an increase in sterol
      ester storage in mutant mice fed a high fat diet. Embryonic fibroblast cells
      transfected with the cholesterol side-chain cleavage system and primary cultures
      of granulosa cells from Mln64 mutant mice showed defects in sterol trafficking as
      reflected in reduced conversion of endogenous cholesterol to steroid hormones.
      These observations suggest that the Mln64 START domain is largely dispensable for
      sterol metabolism in mice.

PMID- 14963027
TI  - Binding of tau to heat shock protein 27 leads to decreased concentration of
      hyperphosphorylated tau and enhanced cell survival.
AB  - Pathological hyperphosphorylated tau is the principal component of paired helical
      filaments, a pathological hallmark of Alzheimer disease (AD) and a strong
      candidate for a neurotoxic role in AD and other neurodegenerative disorders. Here
      we show that heat shock protein 27 (Hsp27) preferentially binds pathological
      hyperphosphorylated tau and paired helical filaments tau directly but not non
      phosphorylated tau. The formation of this complex altered the conformation of
      pathological hyperphosphorylated tau and reduced its concentration by
      facilitating its degradation and dephosphorylation. Moreover, Hsp27 rescues
      pathological hyperphosphorylated tau-mediated cell death. Therefore, Hsp27 is
      likely to provide a neuroprotective effect in AD and other tauopathies.

PMID- 14963028
TI  - The F subunit of Thermus thermophilus V1-ATPase promotes ATPase activity but is
      not necessary for rotation.
AB  - V(1)-ATPase from the thermophilic bacterium Thermus thermophilus is a molecular
      rotary motor with a subunit composition of A(3)B(3)DF, and its central rotor is
      composed of the D and F subunits. To determine the role of the F subunit, we
      generated an A(3)B(3)D subcomplex and compared it with A(3)B(3)DF. The ATP
      hydrolyzing activity of A(3)B(3)D (V(max) = 20 s(-1)) was lower than that of
      A(3)B(3)DF (V(max) = 31 s(-1)) and was more susceptible to MgADP inhibition
      during ATP hydrolysis. A(3)B(3)D was able to bind the F subunit to form
      A(3)B(3)DF. The C-terminally truncated F((Delta85-106)) subunit was also bound to
      A(3)B(3)D, but the F((Delta69-106)) subunit was not, indicating the importance of
      residues 69-84 of the F subunit for association with A(3)B(3)D. The ATPase
      activity of A(3)B(3)DF((Delta85-106)) (V(max) = 24 s(-1)) was intermediate
      between that of A(3)B(3)D and A(3)B(3)DF. A single molecule experiment showed the
      rotation of the D subunit in A(3)B(3)D, implying that the F subunit is a
      dispensable component for rotation itself. Thus, the F subunit binds peripherally
      to the D subunit, but promotes V(1)-ATPase catalysis.

PMID- 14963029
TI  - Conservation of critical functional domains in murine plasminogen activator
      inhibitor-1.
AB  - Plasminogen activator inhibitor-1 is the main physiological regulator of tissue
      type plasminogen activator in normal plasma. In addition to its critical function
      in fibrinolysis, plasminogen activator inhibitor-1 has been implicated in roles
      in other physiological and pathophysiological processes. To investigate structure
      function aspects of mouse plasminogen activator inhibitor-1, the recombinant
      protein was expressed in Escherichia coli and purified. Five variant recombinant
      murine proteins (R76E, Q123K, R346A, R101A, and Q123K/R101A) were also generated
      using site-directed mutagenesis. The variant (R346A) was found to be defective in
      its inhibitory activity against tissue plasminogen activator relative to its wild
      type counterpart. Enzyme-linked immunosorbent assay and surface plasmon resonance
      experiments demonstrated reduced vitronectin-binding affinity of the (Q123K)
      variant (K(D) = 1800 nm) relative to the wild-type protein (K(D) = 5.4 nm).
      Kinetic analyses indicated that the (Q123K) variant had a slower association
      (k(on) = 2.92 x 10(4) m(-1) s(-1)) to, and a faster dissociation from,
      vitronectin (k(off) = 5.3 x 10(-2) s(-1)), (wild-type k(on) = 1.03 x 10(6) m(-1)
      s(-1) and k(off) = 5.27 x 10(-3) s(-1)). The Q123K/R101A variant demonstrated an
      even lower vitronectin-binding ability. Low density lipoprotein receptor-related
      protein binding was decreased for the (R76E) variant. It was also demonstrated
      that the plasminogen activator inhibitor-1/vitronectin complex decreased the
      interaction of plasminogen activator inhibitor-1 with low density lipoprotein
      receptor-related protein. These results indicate that the complex interactions
      traditionally associated with different plasminogen activator inhibitor-1
      functions apply to the murine system, thus showing a commonality of subtle
      functions among different species and evolutionary conservation of this protein.
      Further, this study provides additional evidence that the human hemostasis system
      can be studied effectively in the mouse, which is a great asset for
      investigations with gene-altered mice.

PMID- 14963030
TI  - Cytosolic phospholipase A2 translocates to forming phagosomes during phagocytosis
      of zymosan in macrophages.
AB  - Resident tissue macrophages mediate early innate immune responses to microbial
      infection. Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) is activated in
      macrophages during phagocytosis of non-opsonized yeast (zymosan) triggering
      arachidonic acid release and eicosanoid production. cPLA(2)alpha translocates
      from cytosol to membrane in response to intracellular calcium concentration
      ([Ca(2+)](i)) increases. Enhanced green fluorescent protein (EGFP)-cPLA(2)alpha
      translocated to forming phagosomes, surrounding the zymosan particle by 5 min and
      completely overlapping with early endosome (Rab5) and plasma membrane (F4/80)
      markers but only partially overlapping with resident endoplasmic reticulum
      proteins (GRP78 and cyclooxygenase 2). EGFP-cPLA(2)alpha also localized to
      membrane ruffles during phagocytosis. Zymosan induced an initial high amplitude
      calcium transient that preceded particle uptake followed by a low amplitude
      sustained calcium increase. Both phases were required for optimal phagocytosis.
      Extracellular calcium chelation prevented only the sustained phase but allowed a
      limited number of phagocytic events, which were accompanied by translocation of
      cPLA(2)alpha to the phagosome although [Ca(2+)](i) remained at resting levels.
      The results demonstrate that cPLA(2)alpha targets the phagosome membrane, which
      may serve as a source of arachidonic acid for eicosanoid production.

PMID- 14963031
TI  - RACK1 regulates specific functions of Gbetagamma.
AB  - We showed previously that Gbetagamma interacts with Receptor for Activated C
      Kinase 1 (RACK1), a protein that not only binds activated protein kinase C (PKC)
      but also serves as an adaptor/scaffold for many signaling pathways. Here we
      report that RACK1 does not interact with Galpha subunits or heterotrimeric G
      proteins but binds free Gbetagamma subunits released from activated
      heterotrimeric G proteins following the activation of their cognate receptors in
      vivo. The association with Gbetagamma promotes the translocation of RACK1 from
      the cytosol to the membrane. Moreover, binding of RACK1 to Gbetagamma results in
      inhibition of Gbetagamma-mediated activation of phospholipase C beta2 and
      adenylyl cyclase II. However, RACK1 has no effect on other functions of
      Gbetagamma, such as activation of the mitogen-activated protein kinase signaling
      pathway or chemotaxis of HEK293 cells via the chemokine receptor CXCR2.
      Similarly, RACK1 does not affect signal transduction through the Galpha subunits
      of G(i), G(s), or G(q). Collectively, these findings suggest a role of RACK1 in
      regulating specific functions of Gbetagamma.

PMID- 14963032
TI  - Galphai1 and Galphai3 differentially interact with, and regulate, the G protein
      activated K+ channel.
AB  - G protein-activated K(+) channels (GIRKs; Kir3) are activated by direct binding
      of Gbetagamma subunits released from heterotrimeric G proteins. In native
      tissues, only pertussis toxin-sensitive G proteins of the G(i/o) family,
      preferably Galpha(i3) and Galpha(i2), are donors of Gbetagamma for GIRK. How this
      specificity is achieved is not known. Here, using a pull-down method, we
      confirmed the presence of Galpha(i3-GDP) binding site in the N terminus of GIRK1
      and identified novel binding sites in the N terminus of GIRK2 and in the C
      termini of GIRK1 and GIRK2. The non-hydrolyzable GTP analog, guanosine 5'-3-O
      (thio)triphosphate, reduced the binding of Galpha(i3) by a factor of 2-4.
      Galpha(i1-GDP) bound to GIRK1 and GIRK2 much weaker than Galpha(i3-GDP). Titrated
      expression of components of signaling pathway in Xenopus oocytes and their
      activation by m2 muscarinic receptors revealed that G(i3) activates GIRK more
      efficiently than G(i1), as indicated by larger and faster agonist-evoked
      currents. Activation of GIRK by purified Gbetagamma in excised membrane patches
      was strongly augmented by coexpression of Galpha(i3) and less by Galpha(i1).
      Differences in physical interactions of GIRK with GDP-bound Galpha subunits, or
      Galphabetagamma heterotrimers, may dictate different extents of Galphabetagamma
      anchoring, influence the efficiency of GIRK activation by Gbetagamma, and play a
      role in determining signaling specificity.

PMID- 14963033
TI  - Ouabain assembles signaling cascades through the caveolar Na+/K+-ATPase.
AB  - Based on the observation that the Na(+)/K(+)-ATPase alpha subunit contains two
      conserved caveolin-binding motifs, we hypothesized that clustering of the
      Na(+)/K(+)-ATPase and its partners in caveolae facilitates ouabain-activated
      signal transduction. Glutathione S-transferase pull-down assay showed that the
      Na(+)/K(+)-ATPase bound to the N terminus of caveolin-1. Significantly, ouabain
      regulated the interaction in a time- and dose-dependent manner and stimulated
      tyrosine phosphorylation of caveolin-1 in LLC-PK1 cells. When added to the
      isolated membrane fractions, ouabain increased tyrosine phosphorylation of
      proteins from the isolated caveolae but not other membrane fractions.
      Consistently, ouabain induced the formation of a Na(+)/K(+)-ATPase-Src-caveolin
      complex in the isolated caveolae preparations as it did in live cells. Finally,
      depletion of either cholesterol by methyl beta-cyclodextrin or caveolin-1 by
      siRNA significantly reduced the caveolar Na(+)/K(+)-ATPase and Src.
      Concomitantly, cholesterol depletion abolished ouabain-induced recruitment of Src
      to the Na(+)/K(+)-ATPase signaling complex. Like depletion of caveolin-1, it also
      blocked the effect of ouabain on ERKs, which was restored after cholesterol
      repletion. Clearly, the caveolar Na(+)/K(+)-ATPase represents the signaling pool
      of the pump that interacts with Src and transmits the ouabain signals.

PMID- 14963034
TI  - Protein kinase D potentiates DNA synthesis induced by Gq-coupled receptors by
      increasing the duration of ERK signaling in swiss 3T3 cells.
AB  - Protein kinase D (PKD) potentiates cellular DNA synthesis in response to G
      protein-coupled receptor (GPCR) agonists but the mechanism(s) involved has not
      been elucidated. Here, we examined whether PKD overexpression in Swiss 3T3 cells
      regulates the activation/inactivation kinetics of the extracellular-regulated
      protein kinase (ERK) in response to the mitogenic GPCR agonists bombesin and
      vasopressin. Addition of bombesin or vasopressin to Swiss 3T3 cells
      overexpressing PKD induced a striking increase in the duration of MEK/ERK/RSK
      activation as compared with cultures of either control Swiss 3T3 cells or Swiss
      3T3 cells expressing a kinase-inactive PKD mutant. In contrast, the duration of
      ERK activation in response to epidermal growth factor, which acts via protein
      kinase C/PKD-independent pathways, was not increased. Furthermore, bombesin or
      vasopressin promoted a striking increase in phosphorylation (at Ser-374) and
      accumulation of c-Fos (the c-fos proto-oncogene product) in Swiss 3T3 cells
      overexpressing wild-type (but not kinase-inactive) PKD. Inhibition of the
      sustained phase of ERK/RSK activation abrogated the increase in c-Fos
      accumulation and DNA synthesis induced by bombesin or vasopressin in PKD
      overexpressing cells. Our results demonstrate that PKD selectively potentiates
      mitogenesis induced by bombesin or vasopressin in Swiss 3T3 cells by increasing
      the duration of MEK/ERK/RSK signaling.

PMID- 14963035
TI  - Formation of factors IXa and Xa by the extrinsic pathway: differential regulation
      by tissue factor pathway inhibitor and antithrombin III.
AB  - The activation of factor X by VIIa/TF and the Xa-dependent inhibition of the
      enzyme complex by tissue factor pathway inhibitor (TFPI) are considered primary
      steps in the initiation of coagulation. IX activation by VIIa/TF is considered to
      contribute catalyst necessary for further Xa production in the ensuing
      amplification phase. We have investigated Xa and IXabeta production by VIIa-TF in
      a system reconstituted with both X and IX and the principal physiologic
      inhibitors of this pathway TFPI and antithrombin III (AT). Kinetic studies
      without inhibitors established that IX and X functioned as competitive alternate
      substrates for VIIa/TF with similar kinetic constants. When both IX and X were
      present, TFPI significantly inhibited the extent of formation of either IXabeta
      or Xa. In contrast, AT rapidly depleted active Xa with a small effect on IXabeta
      formation. When both AT and TFPI were present, active IXabeta formation
      significantly exceeded the formation of active Xa regardless of the VIIa/TF
      concentration. These findings could be quantitatively accounted for by a model
      encompassing the kinetics of the individual activation and inhibition steps.
      Active Xa formation by this pathway is regulated in a principal way by its rapid
      inactivation by AT. In contrast, the Xa-dependent inhibitory reactions of TFPI
      play a primary role in limiting zymogen consumption and the formation of active
      IXabeta. These regulatory phenomena yield active IXabeta as a major rather than
      secondary product of VIIa/TF. Our findings raise the possibility that IXabeta
      produced by the extrinsic pathway, and its ability to function within the
      intrinsic Xase complex to activate X may play a significant role in producing Xa
      necessary for both the initiation and sustained phases of the procoagulant
      response following vascular damage.

PMID- 14963036
TI  - The role of Bacillus thuringiensis Cry1C and Cry1E separate structural domains in
      the interaction with Spodoptera littoralis gut epithelial cells.
AB  - The Bacillus thuringiensis delta-endotoxins Cry1C and Cry1E share toxicity
      against several important lepidopteran species. Their combined use to delay
      development of resistance in target insects depends on their differential
      interaction with the gut epithelial cells. The three structural domains and
      combinations of two consecutive domains of Cry1C and Cry1E were separately
      expressed in Escherichia coli, and their interactions with the brush border
      membrane vesicles (BBMV) of Cry1E-tolerant and -susceptible Spodoptera littoralis
      larvae were studied. About 80% reduction in binding of Cry1E and each of its
      separate domains to BBMV of Cry1E-tolerant larvae was observed, whereas Cry1C was
      toxic to all larvae and bound equally to BBMV derived from both Cry1E-tolerant
      and -susceptible larvae. These results suggest differential interactions of the
      two toxins with BBMV encompassing all three domains. Comparable binding assays
      performed with fluorescent Cry1C and Cry1C domain II showed that Cry1C has higher
      Bmax and lower Kd than Cry1C domain II and further supported the existence of
      toxin multisite interactions. Competitive binding assays were used to estimate
      the sequence of interaction events. Cry1C domain II could compete with domain III
      binding, whereas domain III did not interfere with domain II binding, indicating
      sequential interactions of domain III and then domain II with the same membrane
      site. No competition between domain II of Cry1C and Cry1E was observed,
      confirming the existence of different domain II binding sites for the two toxins.
      Taken together, all three domains specifically interact with the epithelial cell
      membrane. The folding of the three-domain toxin probably dictates the sequence of
      interaction events.

PMID- 14963037
TI  - Stochastic variation in telomere shortening rate causes heterogeneity of human
      fibroblast replicative life span.
AB  - The replicative life span of human fibroblasts is heterogeneous, with a fraction
      of cells senescing at every population doubling. To find out whether this
      heterogeneity is due to premature senescence, i.e. driven by a nontelomeric
      mechanism, fibroblasts with a senescent phenotype were isolated from growing
      cultures and clones by flow cytometry. These senescent cells had shorter
      telomeres than their cycling counterparts at all population doubling levels and
      both in mass cultures and in individual subclones, indicating heterogeneity in
      the rate of telomere shortening. Ectopic expression of telomerase stabilized
      telomere length in the majority of cells and rescued them from early senescence,
      suggesting a causal role of telomere shortening. Under standard cell culture
      conditions, there was a minor fraction of cells that showed a senescent phenotype
      and short telomeres despite active telomerase. This fraction increased under
      chronic mild oxidative stress, which is known to accelerate telomere shortening.
      It is possible that even high telomerase activity cannot fully compensate for
      telomere shortening in all cells. The data show that heterogeneity of the human
      fibroblast replicative life span can be caused by significant stochastic cell-to
      cell variation in telomere shortening.

PMID- 14963038
TI  - Pyk2 amplifies epidermal growth factor and c-Src-induced Stat3 activation.
AB  - Signal transducers and activators of transcription factors (STATs) mediate many
      of the cellular responses that occur following cytokine, growth factor, and
      hormone signaling. STATs are activated by tyrosine and serine phosphorylation,
      which normally occurs as a tightly regulated process. Dysregulated STAT activity
      may facilitate oncogenesis, as constitutively activated STATs have been found in
      many human tumors as well as in v-abl- and v-src-transformed cell lines. Pyk2 is
      a member of the focal adhesion kinase family and can be activated by c-Src,
      epidermal growth factor receptor (EGFR), Janus kinase 1, tyrosine kinases, and G
      protein-coupled receptor signaling. Although Pyk2 has been implicated in Janus
      kinase-dependent activation of MAPK and Stat1, no role for Pyk2 in the activation
      of other STAT proteins has been ascribed. Here, we provide evidence that Pyk2,
      along with c-Src, facilitates EGFR-mediated Stat3 activation. Pyk2 expression in
      HeLa cells induces Stat3 reporter gene activation and Stat3 phosphorylation on
      amino acid residues Tyr-705 and Ser-727. Together Pyk2 and c-Src potently
      activate Stat3, and Pyk2 enhances Stat3-induced cell proliferation. Moreover, the
      expression of a dominant negative version of Pyk2 impairs c-Src-induced Stat3
      activation and cell proliferation. The treatment of A431 cells with EGF results
      in the recruitment of c-Src, Pyk2, and Stat3 to the EGFR and the phosphorylation
      of c-Src, Pyk2, and Stat3. Expression of constructs for dominant negative forms
      of either Pyk2 or c-Src impair EGF-induced Stat3 phosphorylation. These results
      indicate that Pyk2 facilitates EGFR- and c-Src-mediated Stat3 activation, thereby
      implicating Pyk2 activation as a potential co-mediator in triggering Stat3
      induced oncogenesis.

PMID- 14963039
TI  - The human antimicrobial peptide LL-37 transfers extracellular DNA plasmid to the
      nuclear compartment of mammalian cells via lipid rafts and proteoglycan-dependent
      endocytosis.
AB  - Antimicrobial peptides, such as LL-37, are found both in nonvertebrates and
      vertebrates, where they represent important components of innate immunity.
      Bacterial infections at epithelial surfaces are associated with substantial
      induction of LL-37 expression, which allows efficient lysis of the invading
      microbes. Peptide-mediated lysis results in the release of bacterial nucleic
      acids with potential pathobiological activity in the host. Here, we demonstrate
      that LL-37 targets extracellular DNA plasmid to the nuclear compartment of
      mammalian cells, where it is expressed. DNA transfer occurred at physiological LL
      37 concentrations that killed bacterial cells, whereas virtually no cytotoxic or
      growth-inhibitory effects were observed in mammalian cells. Furthermore, LL-37
      protected DNA from serum nuclease degradation. LL-37.DNA complex uptake was a
      saturable time- and temperature-dependent process and was sensitive to
      cholesterol-depleting agents that are known to disrupt lipid rafts and caveolae,
      as shown by flow cytometry. Confocal fluorescence microscopy studies showed
      localization of internalized DNA to compartments stained by cholera toxin B, a
      marker of lipid rafts, but failed to demonstrate any co-localization of
      internalized DNA with caveolin-positive endocytotic vesicles. Moreover, LL-37
      mediated plasmid uptake and reporter gene expression were strictly dependent on
      cell surface proteoglycans. We conclude that the human antimicrobial peptide LL
      37 binds to, protects, and efficiently targets DNA plasmid to the nuclei of
      mammalian cells through caveolae-independent membrane raft endocytosis and cell
      surface proteoglycans.

PMID- 14963040
TI  - The von Hippel-Lindau tumor suppressor protein is a molten globule under native
      conditions: implications for its physiological activities.
AB  - The von-Hippel Lindau tumor suppressor protein (pVHL) is conserved throughout
      evolution, as its homologues are found in organisms ranging from mammals to the
      Drosophila melanogaster and Anopheles gambiae insects and the Caenorhabditis
      elegans nematode. Although the physiological role of pVHL is not fully
      understood, it has been shown to interact with a large number of unrelated
      proteins and was suggested to play a role in protein degradation as an E3
      ubiquitin ligase component in the ubiquitin pathway. To gain insight into the
      molecular basis of pVHL activity, we analyzed its folding and stability in
      solution under physiologically relevant conditions. Dynamic light-scattering and
      gel filtration chromatography of the purified pVHL clearly indicated that the
      Stokes radius of the protein is larger than what would be expected from its
      crystal structure. However, under these conditions, the protein shows a clear
      secondary structure as determined by far-UV circular dichroism. Yet, the near-UV
      CD experiments show an absence of a tertiary structure. Upon the addition of
      urea, even at very low concentrations, the protein unfolds in a non-reversible
      manner, leading to the formation of amorphous aggregates. Furthermore, a large
      increase in fluorescence (>50-fold) is observed upon the addition of pVHL into a
      solution containing 8-anilino-1-naphthalene sulfonic acid. We therefore conclude
      that, under native conditions, the non-bound pVHL has a molten globule
      configuration with marginal stability. Although molten globular structures can be
      induced in many proteins under extreme conditions, this is one of the few
      reported cases of such a structure under the physiological conditions of pH,
      ionic strength, and temperature. The significance of the pVHL structural
      properties is being discussed in the context of its physiological activities.

PMID- 14963041
TI  - Vanilloid receptor 1 regulates multiple calcium compartments and contributes to
      Ca2+-induced Ca2+ release in sensory neurons.
AB  - Vanilloid receptor 1 belongs to the transient receptor potential ion channel
      family and transduces sensations of noxious heat and inflammatory hyperalgesia in
      nociceptive neurons. These neurons contain two vanilloid receptor pools, one in
      the plasma membrane and the other in the endoplasmic reticulum. The present
      experiments characterize these two pools and their functional significance using
      calcium imaging and 45Ca uptake in stably transfected cells or dorsal root
      ganglion neurons. The plasma membrane localized receptor is directly activated by
      vanilloids. The endoplasmic reticulum pool was demonstrated to be independently
      activated with 20 microm capsaicin or 1.6 microm resiniferatoxin using a bathing
      solution containing 10 microm Ruthenium Red (to selectively block plasma membrane
      localized receptors) and 100 microm EGTA. We also demonstrate an overlap between
      the endoplasmic reticulum-localized vanilloid receptor regulated stores and
      thapsigargin-sensitive stores. Direct depletion of calcium via activation of
      endoplasmic reticulum-localized vanilloid receptor 1 triggered store operated
      calcium entry. Furthermore, we found that, in the presence of low extracellular
      calcium (10(-5) m), either 2 microm capsaicin or 0.1 nm-1.6 microm
      resiniferatoxin caused a pronounced calcium-induced calcium release in either
      vanilloid receptor-expressing neurons or heterologous expression systems. This
      phenomenon may allow new insight into how nociceptive neuron function in response
      to a variety of nociceptive stimuli both acutely and during prolonged nociceptive
      signaling.

PMID- 14963042
TI  - Pleckstrin homology and phosphotyrosine-binding domain-dependent membrane
      association and tyrosine phosphorylation of Dok-4, an inhibitory adapter molecule
      expressed in epithelial cells.
AB  - Dok-like adapter molecules represent an expanding family of pleckstrin homology
      (PH) and phosphotyrosine-binding (PTB) domain-containing tyrosine kinase
      substrates with negative regulatory functions in hematopoietic cell signaling. In
      a search for nonhematopoietic counterparts to Dok molecules, we identified and
      characterized Dok-4, a recently cloned member of the family. dok-4 mRNA was
      strongly expressed in nonhematopoietic organs, particularly the intestine,
      kidney, and lung, whereas both mRNA and protein were expressed at high levels in
      cells of epithelial origin. In Caco-2 human colon cancer cells, endogenous Dok-4
      underwent tyrosine phosphorylation in response to pervanadate stimulation. In
      transfected COS cells, Dok-4 was a substrate for the cytosolic tyrosine kinases
      Src and Fyn as well as for Jak2. Dok-4 could also be phosphorylated by the
      receptor tyrosine kinase Ret but not by platelet-derived growth factor receptor
      beta or IGF-IR. In both mammalian cells and yeast, Dok-4 was constitutively
      localized at the membrane in a manner that required both its PH and PTB domains.
      The PH and PTB domains of Dok-4 were also required for tyrosine phosphorylation
      of Dok-4 by Fyn and Ret. Finally, wild type Dok-4 strongly inhibited activation
      of Elk-1 induced by either Ret or Fyn. The attenuation of this inhibitory effect
      by deletion of the PH domain and its restoration by the addition of a
      myristoylation signal suggested an important role for constitutive membrane
      localization of Dok-4. In summary, Dok-4 is a constitutively membrane-localized
      adapter molecule that may function as an inhibitor of tyrosine kinase signaling
      in epithelial cells.

PMID- 14963043
TI  - Tumor necrosis factor alpha activates the human plasminogen activator inhibitor-1
      gene through a distal nuclear factor kappaB site.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is the major inhibitor of plasminogen
      activation and likely plays important roles in coronary thrombosis and
      arteriosclerosis. Tumor necrosis factor-alpha (TNFalpha) is one of many
      recognized physiological regulators of PAI-1 expression and may contribute to
      elevated plasma PAI-1 levels in sepsis and obesity. Although TNFalpha is a potent
      inducer of PAI-1 expression in vitro and in vivo, the precise location of the
      TNFalpha response site in the PAI-1 promoter has yet to be determined. Transient
      transfection studies using luciferase reporter constructs containing PAI-1
      promoter sequence up to 6.4 kb failed to detect a response to TNFalpha. Moreover,
      TNFalpha failed to induce expression of enhanced green fluorescent protein under
      the control of a 2.9-kb human PAI-1 promoter in transgenic mice, although
      endogenous murine PAI-1 was strongly induced. These data suggested that the
      TNFalpha response element in the PAI-1 gene is remote from the proximal promoter
      region. In this study, seven candidate regulatory regions were identified using
      cross-species sequence homology analysis as well as DNase I-hypersensitive site
      analysis. We identified a 5' distal TNFalpha-responsive enhancer of the PAI-1
      gene located 15 kb upstream of the transcription start site containing a
      conserved NFkappaB-binding site that mediates the response to TNFalpha. This
      newly recognized site is fully capable of binding NFkappaB subunits p50 and p65,
      whereas overexpression of the NFkappaB inhibitor IkappaB prevents TNFalpha
      induced activation of this enhancer element.

PMID- 14963044
TI  - Opening of the mitochondrial permeability transition pore induces reactive oxygen
      species production at the level of the respiratory chain complex I.
AB  - We have investigated the consequences of permeability transition pore (PTP)
      opening on the rate of production of reactive oxygen species in isolated rat
      liver mitochondria. We found that PTP opening fully inhibited H(2)O(2) production
      when mitochondria were energized both with complex I or II substrates. Because
      PTP opening led to mitochondrial pyridine nucleotide depletion, H(2)O(2)
      production was measured again in the presence of various amounts of NADH. PTP
      opening-induced H(2)O(2) production began when NADH concentration was higher than
      50 microm and reached a maximum at over 300 microm. At such concentrations of
      NADH, the maximal H(2)O(2) production was 4-fold higher than that observed when
      mitochondria were permeabilized with the channel-forming antibiotic alamethicin,
      indicating that the PTP opening-induced H(2)O(2) production was not due to
      antioxidant depletion. Moreover, PTP opening decreased rotenone-sensitive NADH
      ubiquinone reductase activity, whereas it did not affect the NADH FeCN reductase
      activity. We conclude that PTP opening induces a specific conformational change
      of complex I that (i) dramatically increases H(2)O(2) production so long as
      electrons are provided to complex I, and (ii) inhibits the physiological pathway
      of electrons inside complex I. These data allowed the identification of a novel
      consequence of permeability transition that may partly account for the mechanism
      by which PTP opening induces cell death.

PMID- 14963045
TI  - Helicobacter pylori CagA induces Ras-independent morphogenetic response through
      SHP-2 recruitment and activation.
AB  - The CagA protein of Helicobacter pylori, which is injected from the bacteria into
      bacteria-attached gastric epithelial cells, is associated with gastric carcinoma.
      CagA is tyrosine-phosphorylated by Src family kinases, binds the SH2 domain
      containing SHP-2 phosphatase in a tyrosine phosphorylation-dependent manner, and
      deregulates its enzymatic activity. We established AGS human gastric epithelial
      cells that inducibly express wild-type or a phosphorylation-resistant CagA, in
      which tyrosine residues constituting the EPIYA motifs were substituted with
      alanines. Upon induction, wild-type CagA, but not the mutant CagA, elicited
      strong elongation of cell shape, termed the "hummingbird" phenotype. Time-lapse
      video microscopic analysis revealed that the CagA-expressing cells exhibited a
      marked increase in cell motility with successive rounds of elongation-contraction
      processes. Inhibition of CagA phosphorylation by an Src kinase inhibitor, PP2, or
      knockdown of SHP-2 expression by small interference RNA (siRNA) abolished the
      CagA-mediated hummingbird phenotype. The morphogenetic activity of CagA also
      required Erk MAPK but was independent of Ras or Grb2. In AGS cells, CagA
      prolonged duration of Erk activation in response to serum stimulation.
      Conversely, inhibition of SHP-2 expression by siRNA abolished the sustained Erk
      activation. Thus, SHP-2 acts as a positive regulator of Erk activity in AGS
      cells. These results indicate that SHP-2 is involved in the Ras-independent
      modification of Erk signals that is necessary for the morphogenetic activity of
      CagA. Our work therefore suggests a key role of SHP-2 in the pathological
      activity of H. pylori virulence factor CagA.

PMID- 14963046
TI  - Conserved nuclear export sequences in Schizosaccharomyces pombe Mex67 and human
      TAP function in mRNA export by direct nuclear pore interactions.
AB  - Mex67, the homolog of human TAP, is not an essential mRNA export factor in
      Schizosaccharomyces pombe. Here we show that S. pombe encodes a homolog of the
      TAP cofactor that we have also named p15, whose function in mRNA export is not
      essential. We have identified and characterized two distinct nuclear export
      activities, nuclear export signal (NES) I and NES II, within the region of amino
      acids 434-509 of Mex67. These residues map within the known NTF2-like fold of TAP
      (amino acids 371-551). We show that the homologs of these two NESs are present
      and are functionally conserved in TAP. The NES I, NES II, and NES I + II of TAP
      and Mex67 directly bind with -phenylalanine-glycine (-FG)-containing sequences of
      S. pombe Nup159 and Nup98 but not with human p62. Mutants of NES I or NES II of
      Mex67/TAP that do not bind -FG Nup159 and Nup98 in vitro are unable to mediate
      nuclear export of a heterologous protein in S. pombe and in HeLa cells. Fused
      with the RNA recognition motifs (RRMs) of Crp79 and green fluorescent protein
      (GFP) (RRM-NES-GFP), the NES I and NES II of Mex67 or TAP can suppress the mRNA
      export defect of the Deltap15 rae1-167 synthetic lethal S. pombe strain,
      suggesting that the NESs can function in the absence of p15. These novel nuclear
      export sequences may provide additional routes for delivering Mex67/TAP to the
      nuclear pore complex.

PMID- 14963047
TI  - Impaired Shc, Ras, and MAPK activation but normal Akt activation in FL5.12 cells
      expressing an insulin-like growth factor I receptor mutated at tyrosines 1250 and
      1251.
AB  - The Y1250F/Y1251F mutant of the insulin-like growth factor I receptor (IGF-IR)
      has tyrosines 1250 and 1251 mutated to phenylalanines and is deficient in IGF-I
      mediated suppression of apoptosis in FL5.12 lymphocytic cells. To address the
      mechanism of loss of function in this mutant we investigated signaling responses
      in FL5.12 cells overexpressing either a wild-type (WT) or Y1250F/Y1251F (mutant)
      IGF-IR. Cells expressing the mutant receptor were deficient in IGF-I-induced
      phosphorylation of the JNK pathway and had decreased ERK and p38 phosphorylation.
      IGF-I induced phosphorylation of Akt was comparable in WT and mutant expressing
      cells. The decreased activation of the mitogen-activated protein kinase (MAPK)
      pathways was accompanied by greatly decreased Ras activation in response to IGF
      I. Although phosphorylation of Gab2 was similar in WT and mutant cell lines,
      phosphorylation of Shc on Tyr(313) in response to IGF-I was decreased in cells
      expressing the mutant receptor, as was recruitment of Grb2 and Ship to Shc.
      However, phosphorylation of Shc on Tyr(239), the Src phosphorylation site, was
      normal. A role for JNK in the survival of FL5.12 cells was supported by the
      observation that the JNK inhibitor SP600125 suppressed IGF-I-mediated protection
      from apoptosis. Altogether these data demonstrate that phosphorylation of Shc,
      and assembly of the Shc complex necessary for activation of Ras and the MAPK
      pathways are deficient in cells expressing the Y1250F/Y1251F mutant IGF-IR. This
      would explain the loss of IGF-I-mediated survival in FL5.12 cells expressing this
      mutant and may also explain why this mutant IGF-IR is deficient in functions
      associated with cellular transformation and cell migration in fibroblasts and
      epithelial tumor cells.

PMID- 14963048
TI  - Glycemic index in the treatment of diabetes: the debate continues.

PMID- 14963049
TI  - Carbohydrate and fiber recommendations for individuals with diabetes: a
      quantitative assessment and meta-analysis of the evidence.
AB  - To review international nutrition recommendations with a special emphasis on
      carbohydrate and fiber, analyze clinical trial information, and provide an
      evidence-based recommendation for medical nutrition therapy for individuals with
      diabetes. Relevant articles were identified by a thorough review of the
      literature and the data tabulated. Fixed-effects meta-analyses techniques were
      used to obtain mean estimates of changes in outcome measures in response to diet
      interventions. Most international organizations recommend that diabetic
      individuals achieve and maintain a desirable body weight with a body mass index
      of </=25 kg/m(2). For diabetic subjects moderate carbohydrate, high fiber diets
      compared to moderate carbohydrate, low fiber diets are associated with
      significantly lower values for: postprandial plasma glucose, total and low
      density lipoprotein cholesterol, high-density lipoprotein cholesterol, and
      triglycerides. High carbohydrate, high fiber diets compared to moderate
      carbohydrate, low fiber diets are associated with lower values for: fasting,
      postprandial and average plasma glucose; hemoglobin A(1c); total, LDL
      cholesterol, HDL-cholesterol and triglycerides. Low glycemic index diets compared
      to high glycemic index diets are associated with lower fasting plasma glucose
      values and lower glycated protein values. Based on these analyses we recommend
      that the diabetic individual should be encouraged to achieve and maintain a
      desirable body weight and that the diet should provide these percentages of
      nutrients: carbohydrate, >/=55%; protein, 12-16%; fat, <30%; and monounsaturated
      fat, 12-15%. The diet should provide 25-50 g/day of dietary fiber (15-25 g/1000
      kcal). Glycemic index information should be incorporated into exchanges and
      teaching material.

PMID- 14963050
TI  - Associations of adequate intake of calcium with diet, beverage consumption, and
      demographic characteristics among children and adolescents.
AB  - OBJECTIVE: The objective of this study is to examine various factors associated
      with total calcium intake and percent adequate intake (% AI) of calcium by
      children and adolescents, with respect to age, gender, race/ethnicity, and diet
      and beverage choices. DESIGN: Data from the U.S. Department of Agriculture's
      Continuing Survey of Food Intake by Individuals 1994-96, 98 were used in the
      analyses. Age groupings (2-3, 4-8, 9-13, and 14-18 year olds) were based on the
      National Academy of Sciences recommendations for AI of calcium-500, 800, 1,300,
      and 1,300 mg calcium per day, respectively. RESULTS: Consumption of milk products
      was strongly and positively associated with calcium intake. Consumption of
      carbonated soft drinks and other non-dairy beverages was also positively
      associated with calcium intake, but this association was very weak. Beverage
      choices of African-American children and adolescents are significantly different
      than white and Hispanic children and adolescents. For example, African-American
      adolescent girls consume fewer milk products and more fruit drinks/ades. Average
      daily carbonated soft drink consumption is approximately 1.6 and 1.0 twelve ounce
      cans among 14-18 year old boys and girls, respectively. CONCLUSION: Carbonated
      soft drink consumption among adolescent girls is modest and does not appear to be
      linked to decreased calcium intake. The analyses in this paper show that creative
      effective, efficient, and targeted policies should be considered to help
      adolescent girls increase calcium intake. Making low-fat milk products, flavored
      milks, calcium-fortified beverages and foods more attractive and available will
      help encourage girls to consume more of this important mineral. When adequate
      calcium intake is not achieved through foods, health professionals should
      consider recommending calcium supplements.

PMID- 14963051
TI  - Low plasma lycopene concentration is associated with increased mortality in a
      cohort of patients with prior oral, pharynx or larynx cancers.
AB  - OBJECTIVE: This analysis was conducted to evaluate the association between plasma
      beta-carotene, alpha-carotene, lycopene, lutein/zeaxanthin, total carotenoids,
      retinol, alpha-tocopherol and subsequent mortality. METHODS: Blood samples
      collected longitudinally from 259 participants in a chemoprevention trial aimed
      at the prevention of second cancers of the oral cavity, pharynx, or larynx were
      analyzed by high performance liquid chromatography for selected micronutrients.
      All-cause mortality (primary outcome) and cause-specific mortality (secondary
      outcomes) were evaluated in relation to plasma micronutrient concentrations at
      baseline and longitudinally. RESULTS: A total of 61 deaths occurred over a follow
      up time of up to 90 months. Cox proportional hazards models with time-dependent
      covariates were used for data analyses. In models adjusted for age, plasma
      cholesterol, time-dependent smoking, treatment arm, study site and gender, only
      plasma lycopene was significantly inversely associated with total mortality
      [hazard ratio (HR) above versus below median = 0.53, 95% confidence interval (CI)
      0.30-0.93]. Plasma alpha-carotene was inversely associated (HR 0.24, 95% CI 0.08
      0.75) while plasma retinol was positively associated (HR 5.12, 95% CI 1.54-17.05)
      with cardiovascular death. Smoking status modified plasma nutrient associations
      with total mortality. Lycopene (HR 0.08, 95% CI 0.02-0.36), alpha-carotene (HR
      0.25, 95% CI 0.09-0.73) and total carotenoids (HR 0.22, 95% CI 0.07-0.70) were
      inversely associated with mortality in non-smokers, while plasma retinol (HR =
      3.56, 95% CI 1.40-9.09) and alpha-tocopherol (HR = 2.47, 95% CI 1.02-5.98) were
      positively associated with mortality in smokers. CONCLUSIONS: Only plasma
      lycopene was significantly associated (inversely) with total mortality in the
      full study population. Smoking modifies associations between nutrients and
      mortality.

PMID- 14963052
TI  - Calcium intake during pregnancy among white and African-American pregnant women
      in the United States.
AB  - OBJECTIVE: To characterize the calcium intake in a racially mixed cohort of
      pregnant women, including the contribution of supplementation and antacids.
      METHODS: A cohort of women was interviewed twice during their pregnancies. The
      interviews included a food frequency questionnaire and questions on calcium
      supplementation and antacid intake. Pregnant women seeking prenatal care at a
      Pittsburgh hospital in the first trimester were enrolled. 454 women were enrolled
      and did not miscarry; 385 completed two interviews and were of white or African
      American race. RESULTS: Mean and median intakes of calcium were 1671 mg/day and
      1482 mg/day. 36% of the women were under the former RDA level (1200 mg/day) for
      calcium, while 26% were under the current AI (1000 mg/day). Six percent were
      taking in less than 600 mg/day, and 15% over 2500 mg/day, the tolerable upper
      limit. Young women were particularly likely to have low intakes (12% of those
      less than 21 years of age had less than 600 mg/day). Black women were slightly
      overrepresented among those with low intake (8% vs. 5% of whites), but, overall,
      their intake was quite similar to whites. Milk and cheese provided more calcium
      than other food items. Many women took antacids, especially during the second
      half of pregnancy, and these were a major source of calcium for some members of
      the cohort. CONCLUSIONS: Although mean and median calcium intake in the cohort
      were above the AI, many women had calcium intakes that were too high or low.
      Dairy products provided the most calcium for most pregnant women, and antacids
      were an important source for many.

PMID- 14963053
TI  - Height-related changes in body mass index: a reappraisal.
AB  - OBJECTIVES: To study the relationship between body mass index (BMI) and height in
      20-22 year-old patients. METHODS: A research questionnaire filled by a
      representative sample of military personnel upon discharge from service was
      analyzed. At the same time, weight and height were measured, and BMI was
      calculated (BMI = weight (Kg)/height(2)(m(2))). RESULTS: There were 35,951
      participants in the study, including 16204 females and 19747 males. There was a
      positive correlation between BMI and height in men (regression slope = 0.00717, r
      = 0.015, p = 0.03), while the correlation was negative in women (regression slope
      = -0.02811, r = -0.05, p < 0.0001). In multiple regression analysis, when BMI was
      used as the dependent variable and height, gender, ethnic origin, smoking, oral
      contraceptive use, and level of recreational exercise as the independent
      variables, only height, gender, and ethnic origin remained significant in the
      final analysis (R-square 0.0205, p < 0.0001). CONCLUSION: In young adults, BMI is
      affected in a subtle, but opposite manner in males and females. In males, BMI
      increases with increasing height, while in females, BMI decreases with increasing
      height.

PMID- 14963054
TI  - Lipids significantly reduced by diets containing barley in moderately
      hypercholesterolemic men.
AB  - OBJECTIVE: To determine whether barley, as the soluble fiber source, would
      beneficially change cardiovascular risk factors. Soluble fiber from oats has been
      recognized as beneficial in decreasing blood cholesterol levels. Although barley
      contains high amounts of soluble fiber, it is not consumed as extensively as
      oats. METHODS: Eighteen moderately hypercholesterolemic men (28-62 y) consumed a
      controlled equilibration diet (Step 1, 30% fat, 55% carbohydrate, 15% protein, <
      300 mg cholesterol) for 2 weeks followed by the diet with about 20% of energy
      replaced with brown rice/whole wheat, (1/2) barley & (1/2) brown rice/whole wheat
      or barley (< 0.4 g, 3 g and 6 g added soluble fiber/2800 kcal, respectively) for
      5 weeks in a Latin square design. Fasting blood was drawn twice weekly. Total
      cholesterol, HDL cholesterol, and triacylglycerols were measured enzymatically
      and lipid fractions were measured by nuclear magnetic resonance spectroscopy.
      RESULTS: Compared with prestudy concentrations, total cholesterol (14%, 17%, and
      20%, respectively) and LDL cholesterol (17%, 17%, and 24%, respectively) were
      significantly lower (p < 0.0001) after the low, medium, and high-soluble fiber
      diets. Triacylglycerol was 6%, 10%, and 16% lower (p = 0.09) whereas HDL
      cholesterol (9%, 7%, and 18%) was higher (p < 0.001) after the experimental
      diets. Total cholesterol and LDL cholesterol after the high-soluble fiber diet
      were significantly lower than concentrations after the low- or medium-soluble
      fiber diets. Mean LDL particle number significantly decreased (p < 0.007) and the
      large LDL cholesterol fraction showed a trend toward lower concentrations (p =
      0.06). CONCLUSION: Increasing soluble fiber through consumption of barley in a
      healthy diet can reduce cardiovascular risk factors.

PMID- 14963055
TI  - Magnesium intake and risk of coronary heart disease among men.
AB  - OBJECTIVE: Our aim in this study was to assess the relationship between magnesium
      intake and risk of coronary heart disease (CHD) among men. METHODS: A total of
      39,633 men in the Health Professionals Follow-up Study who returned a dietary
      questionnaire in 1986 were followed up for 12 years. Intakes of magnesium, zinc
      and potassium and other nutrients were assessed in 1986, 1990 and 1994. Total CHD
      incidence (nonfatal myocardial infarction (MI) and fatal CHD) was ascertained by
      biennial questionnaire and mortality surveillance confirmed by medical record
      review. Standard CHD risk factors were recorded biennially. RESULTS: During 12
      years of follow-up (414,285 person-years), we documented 1,449 cases of total CHD
      (1,021 non-fatal MI cases, and 428 fatal CHD). The age-adjusted relative risk
      (RR) of developing CHD in the highest quintile (median intake = 457 mg/day)
      compared with the lowest quintile (median intake = 269 mg/day) was 0.73 (95% CI
      0.62-0.87, p for trend <0.0001). After controlling for standard CHD risk factors
      and dietary factors, the RR for developing CHD among men in the highest total
      magnesium intake quintile compared with those in the lowest was 0.82 (95% CI 0.65
      1.05, p for trend = 0.08). For supplemental magnesium intake, the RR comparing
      the highest quintile to non-supplement users was 0.77 (95% CI 0.56-1.06, p for
      trend = 0.14). CONCLUSIONS: These results suggest that intake of magnesium may
      have a modest inverse association with risk of CHD among men.

PMID- 14963056
TI  - Eicosapentaenoic acid prevents LPS-induced TNF-alpha expression by preventing NF
      kappaB activation.
AB  - BACKGROUND: Many studies have shown that fish oil supplementation inhibits tumor
      necrosis factor-alpha (TNF-alpha) production in mice and human subjects; however,
      the mechanisms remain unclear. Nuclear factor-kappaB (NF-kappaB) is a
      transcription factor that plays an important role in controlling the expression
      of pro-inflammatory genes including TNF-alpha. Activation of NF-kappaB has been
      shown to mediate the maximal expression of TNF-alpha in human monocytes. NF
      kappaB is kept in an inactive form in the cytoplasm by IkappaB, the inhibitory
      subunit of NF-kappaB complex. Phosphorylation and subsequent degradation of
      IkappaB lead to NF-kappaB activation. OBJECTIVES: The effect of eicosapentaenoic
      acid (EPA), a major n-3 fatty acid in fish oil, on the lipopolysaccharide (LPS)
      induced expression of TNF-alpha and activation of NF-kappaB were investigated.
      The mechanism underlying EPA modulation of NF-kappaB activation was also studied.
      METHODS: Human monocytic THP-1 cells were pre-incubated with EPA and stimulated
      with LPS. The levels of secreted TNF-alpha were determined by ELISA. The DNA
      binding activity of NF-kappaB was analyzed by EMSA. The degradation and
      phosphorylation of IkappaB-alpha were examined by Western blot analysis. RESULTS:
      TNF-alpha production and expression induced by LPS were significantly decreased
      in cells pre-incubated with EPA. LPS-induced NF-kappaB activation, translocation
      of p65 subunit to the nucleus, phosphorylation and degradation of IkappaB-alpha
      were partially prevented by EPA. CONCLUSIONS: The results suggest that
      suppression of the TNF-alpha expression by EPA is partly attributed to its
      inhibitory effect on NF-kappaB activation. EPA appears to prevent NF-kappaB
      activation by preventing the phosphorylation of IkappaB-alpha.

PMID- 14963057
TI  - Validation of bone mass and body composition measurements in small subjects with
      pencil beam dual energy X-ray absorptiometry.
AB  - OBJECTIVE: To validate the most widely reported dual energy X-ray absorptiometry
      (DXA) technique for the measurement of bone mass and body composition in human
      infants with a piglet model. METHODS: Duplicate scans were obtained in 13 piglets
      (1950g to 21100g) using a whole body densitometer (Hologic QDR 2000 plus, Hologic
      Inc., Waltham, MA) operated in the pencil-beam mode on a two platform (aluminum
      platform overlying a foam table pad) system. DXA measurements that included total
      weight, bone mineral content, fat and lean mass were compared with carcass weight
      and chemical analysis for ash and calcium content, fat and lean mass. RESULTS:
      Measurements from duplicate DXA scans were nearly perfectly correlated (r = 0.98
      to 1.00). DXA measurements were strongly predictive of scale weight and chemical
      composition for all piglets (adjusted r(2) = 0.93 to 1.00, intraclass reliability
      coefficients = 0.943 to 0.999, p < 0.001 for all comparisons) although DXA bone
      mineral content consistently underestimated carcass ash and calcium content.
      Measured values from heavier piglets were not significantly different from values
      predicted from the lighter piglets' data. Slopes from regression based on lighter
      versus heavier piglets were not significantly different except for the bone
      mineral content with carcass ash or calcium content. CONCLUSION: Our study
      validated the use of pencil beam DXA and its ability to determine relative
      changes in bone mass and body composition measurements over a much greater range
      of body weight than previous reports although its use as a direct indicator of
      nutrient requirement may be limited.

PMID- 14963058
TI  - Effects of dietary intake of soy protein and isoflavones on cardiovascular
      disease risk factors in high risk, middle-aged men in Scotland.
AB  - OBJECTIVE: To investigate the effects of soy protein and isoflavones on blood
      pressure (BP) and cholesterol levels among high risk middle-aged Scottish men.
      DESIGN: A randomized, double-blind, placebo-controlled, parallel-group dietary
      intervention study SETTING: Inhabitants on Isles of Lewis and Harris in Scotland
      SUBJECTS: Sixty-one men with relatively higher BP and/or total cholesterol (TC)
      levels aged 45 to 59 went through the dietary intervention. INTERVENTION: Diets
      containing at least 20 g of soy protein and 80 mg of isoflavones were compared to
      the placebo diets. Intervention period was 5 weeks duration. RESULTS: Significant
      difference was found in 24-hour urinary isoflavone excretion between the two
      groups after intervention. Significant reductions from the baselines were
      observed in systolic BP (SBP) and diastolic BP (DBP), TC and non-high density
      lipoprotein cholesterol (non-HDL-C) in the soy-containing diet group, but not in
      the olive oil containing active placebo group. Significant increases in high
      density lipoprotein cholesterol (HDL-C) were observed in both groups. CONCLUSION:
      Dietary intakes of soy protein (at least 20 g) and isoflavones (at least 80 mg)
      for 5 weeks would be effective in reducing CHD risk among high-risk, middle-aged
      men.

PMID- 14963060
TI  - Prevalence of dfr genes associated with integrons and dissemination of dfrA17
      among urinary isolates of Escherichia coli in Korea.
AB  - OBJECTIVES: The association of trimethoprim-resistant dfr genes with integrons
      was investigated in urinary Escherichia coli isolates in Korea from the last two
      decades. METHODS: Of 623 E. coli isolates from urine specimens, 421 trimethoprim
      resistant isolates were studied for dfr genes associated with integrons.
      Integrase genes were amplified and the PCR products restricted using HinfI to
      classify integron types. Gene cassette regions for the class 1 and class 2
      integrons were amplified and sequenced. PFGE was performed to determine the
      epidemiological relationship of E. coli isolates. RESULTS: The carriage of class
      1 integrons was found to be significantly higher in trimethoprim-resistant
      isolates (69%) than in trimethoprim-susceptible isolates (19%). Among the
      trimethoprim-resistant isolates, the frequency of dfr genes associated with class
      1 integrons increased sharply from 10% of the isolates during 1980-1985 to 53%
      during 1996-1997 and to 46% during 2001-2002. Five different dfr cassettes-
      dfrA1, dfrA5, dfrA7, dfrA12 and dfrA17--were identified among the urinary E. coli
      isolates from the last two decades; dfrA12 was the most prevalent during 1980
      1985 and dfrA17 during 1996-1997 and 2001-2002. The majority of dfr genes
      associated with class 1 integrons were conjugally transferable to recipient E.
      coli strains. The E. coli isolates that carried dfrA17 associated with class 1
      integrons were found to be phylogenetically unrelated, indicating that dfrA17 was
      widely distributed in the different clones of E. coli. CONCLUSION: Class 1
      integrons were found to be an important genetic element of resistance to
      trimethoprim among urinary E. coli in Korea, and the prevalence of dfrA17 was
      mainly due to the horizontal transfer of class 1 integrons through conjugative
      plasmids.

PMID- 14963061
TI  - Analysis of protease inhibitor combinations in vitro: activity of lopinavir,
      amprenavir and tipranavir against HIV type 1 wild-type and drug-resistant
      isolates.
AB  - BACKGROUND: Despite the increasing number of antiretroviral compounds, the number
      of useful drug regimens is limited owing to the high frequency of cross
      resistance. PATIENTS AND METHODS: We studied in vitro two-drug combinations using
      three protease inhibitors (PIs), tipranavir, amprenavir and lopinavir, on
      isolates (003 and 004) derived from patients with resistance to multiple PIs
      compared with the drug-susceptible isolate 14aPre in peripheral blood mononuclear
      cells. Drug interactions were determined by median dose-effect analysis, with the
      combination index calculated at several inhibitory concentrations (IC). RESULTS:
      In 14aPre experiments, the combination tipranavir + lopinavir demonstrated
      synergy at low concentrations (IC(50)), an additive effect at IC(75) and
      antagonism at IC(90)-IC(95); tipranavir + amprenavir were antagonistic at all
      concentrations except IC(95), where they were synergic; and the lopinavir +
      amprenavir combination was always antagonistic. In 003 and 004 infections,
      tipranavir + lopinavir and tipranavir + amprenavir combinations were
      antagonistic, and lopinavir + amprenavir were synergic, at all concentrations,
      with the exception of being additive at IC(95). CONCLUSIONS: Our in vitro
      experiments did not show any advantage in combining second generation PIs as a
      therapeutic strategy in naive or multi-treatment failure subjects, with the
      exception of tipranavir + amprenavir at IC(95) in infections by a wild-type
      isolate.

PMID- 14963062
TI  - Daptomycin synergy with rifampicin and ampicillin against vancomycin-resistant
      enterococci.
AB  - We used a novel screening method to look for synergy between daptomycin and 18
      other antibiotics against 19 strains of high-level vancomycin-resistant
      enterococci (VRE) (vancomycin MIC > or = 256 mg/L). In this approach, daptomycin
      was incorporated into Ca(2+)-supplemented Mueller-Hinton agar at subinhibitory
      concentrations, and synergy was screened by comparing test antibiotic Etest MICs
      on agar with and without daptomycin. A striking reduction in the rifampicin MIC
      was seen in 11/15 (73.3%) VRE that were resistant to rifampicin, from > or =12
      mg/L to a mean +/- s.d. of 0.22 +/- 0.21 mg/L at daptomycin 0.25 x MIC and 0.85
      +/- 0.90 mg/L at daptomycin 0.125 x MIC. Synergy was also observed for 13/19
      (68%) isolates with ampicillin (MIC > or = 128 mg/L). There was no significant
      synergy between daptomycin and any other antibiotic by this screening method. If
      confirmed by further studies, daptomycin with either rifampicin or ampicillin may
      be useful in the management of infections caused by VRE.

PMID- 14963063
TI  - Inverse correlation between CD8+ lymphocyte apoptosis and CD4+ cell counts during
      potent antiretroviral therapy in HIV patients.
AB  - OBJECTIVES: We have addressed the relationships between inhibition of CD4+ and
      CD8+ cell apoptosis and CD4+ cell recovery in HIV patients undergoing potent
      antiretroviral therapy (PART) by correlating apoptosis levels with virological
      and immunological parameters detected over a long-term period in HIV patients
      undergoing therapy. PATIENTS AND METHODS: Twenty-two HIV-1-infected patients
      undergoing PART were enrolled in a long-term, open longitudinal study. Data
      derived from 17 patients with successful response to therapy (TS; median time of
      follow-up 36 months, range 24-36 months) were used for correlation studies.
      Apoptosis was evaluated after short-term culture of peripheral blood lymphocytes
      by flow cytometry analysis of isolated nuclei or of annexin V/CD4, annexin V/CD8
      double-stained cells. RESULTS: Sustained, noticeable levels of apoptosis
      inhibition in peripheral blood mononuclear cells were measured, in the long-term,
      in 16 of the 17 TS patients. Levels of total cell apoptosis correlated with
      levels of CD8+ apoptotic cells more significantly than with levels of CD4+
      apoptotic cells. In addition, CD4+ cell counts were correlated inversely with
      levels of CD8+ apoptotic cells in a highly significant fashion, but not with
      levels of CD4+ apoptotic cells. CONCLUSIONS: Our data indicate that the increase
      of CD4+ lymphocytes in HIV patients, as a consequence of successful response to
      PART, may be related to changes in apoptosis level occurring in the CD8+, and not
      in the CD4+, cell compartment.

PMID- 14963064
TI  - Susceptibility of clinical isolates of Candida lusitaniae to five systemic
      antifungal agents.
AB  - OBJECTIVES: The aim of the present study was to expand the MIC database for
      Candida lusitaniae in order to further determine its antifungal susceptibility
      pattern. METHODS: The activities of amphotericin B, fluconazole, itraconazole,
      voriconazole and flucytosine were determined in vitro against 80 clinical
      isolates of C. lusitaniae. A set of 59 clinical isolates of Candida albicans and
      of 51 isolates of Candida glabrata was included to compare the susceptibilities
      to amphotericin B. The MICs were determined by Etest with RPMI 1640 agar, and
      with both this medium and antibiotic medium 3 (AM3) agar for testing of
      amphotericin B. RESULTS: All isolates were highly susceptible to fluconazole. The
      susceptibility to itraconazole was good; only 4% of isolates had dose-dependent
      susceptibility (MICs 0.25-0.5 mg/L). Voriconazole was very active in vitro (100%
      of isolates were inhibited at < or =0.094 mg/L). Flucytosine MICs ranged widely
      (0.004->32 mg/L). The set included 19% of flucytosine-resistant isolates. For
      amphotericin B, 100% of isolates were inhibited at < or =0.75 mg/L (MIC(50) 0.047
      mg/L; MIC(90) 0.19 mg/L) and at < or =4 mg/L (MIC(50) 0.25 mg/L; MIC(90) 0.75
      mg/L) on RPMI and on AM3, respectively. A single isolate was categorized as
      resistant to amphotericin B (MIC 0.75 and 4 mg/L on RPMI and on AM3,
      respectively). Amphotericin B thus appeared very active in vitro against C.
      lusitaniae. Whatever the test medium, the level of susceptibility of C.
      lusitaniae to amphotericin B did not differ much from those of C. albicans and C.
      glabrata. CONCLUSION: C. lusitaniae appears to be susceptible to amphotericin B,
      azole antifungal agents, and, to a lesser extent, flucytosine.

PMID- 14963065
TI  - Oral anti-pneumococcal activity and pharmacokinetic profiling of a novel peptide
      deformylase inhibitor.
AB  - OBJECTIVE: BB-81384, a novel peptide deformylase (PDF) inhibitor, was
      characterized in terms of enzyme inhibition profile, antibacterial activity,
      rodent pharmacokinetics and oral efficacy in murine infection models. METHODS:
      MICs were determined by standard NCCLS broth microdilution. Selectivity of
      metalloenzyme inhibition was determined with a limited panel of enzymes via
      standard biochemical assays. Profiling of the pharmacokinetics and select tissue
      disposition in mice was determined and compared with that of the macrolide,
      azithromycin. In vivo murine efficacy studies using Streptococcus pneumoniae were
      conducted using a peritonitis model, as well as lung and thigh burden models of
      infection. RESULTS: BB-81384 selectively inhibited PDF with an IC(50)
      approximately 10 nM and with MICs < 0.5 mg/L against most S. pneumoniae
      pathogens. Pharmacokinetic analysis revealed good oral bioavailability and
      moderate clearance and volume of distribution. BB-81384 partitioning to lung
      tissue was similar in terms of magnitude and kinetics to that of the plasma
      compartment. Single-administration oral efficacy in a mouse peritonitis model was
      evident with an ED(50) of 30 mg/kg. BB-81384 reduced the bacterial load by
      approximately 5 and 3 log units in organ-burden models of lung and thigh
      infection, respectively. CONCLUSION: BB-81384, a novel PDF inhibitor with good
      activity against S. pneumoniae in vitro, was the first compound of this class to
      be profiled for oral pharmacokinetics and tissue disposition and to demonstrate
      oral anti-pneumococcal efficacy in mice.

PMID- 14963066
TI  - Diffusion of levofloxacin into bone and synovial tissues.
AB  - OBJECTIVES: The degree of penetration of an antibiotic into the infected site is
      an important determinant of therapeutic success. Levofloxacin is widely used in
      the treatment of serious infections. However, there are only few studies
      concerning its diffusion into bone tissue and none concerning its diffusion into
      synovial tissue. Our objective was to quantify levofloxacin bone and synovial
      tissue penetration and to compare our data with the breakpoint for susceptible
      organisms. PATIENTS AND METHODS: In an open-label study, 12 subjects who were
      undergoing elective total hip replacement received a single, parenteral, 500 mg
      dose of levofloxacin. Plasma, cortical and cancellous bone, and synovial tissue
      samples were collected a mean of 1.2 h later and analysed by a validated HPLC
      method. RESULTS: The mean +/- S.D. plasma concentration of levofloxacin at the
      time of bone removal was 7.5 +/- 1.3 mg/L. The levofloxacin concentrations were
      7.4 +/- 2.2 mg/kg in cancellous bone tissue and 3.9 +/- 1.2 mg/kg in cortical
      bone tissue. The levofloxacin concentration was 8.9 +/- 2.1 mg/kg in synovial
      tissue. The mean +/- S.D. ratios of levofloxacin concentration in bone and plasma
      (bone/plasma) were 1.0 +/- 0.4 for cancellous bone tissue and 0.5 +/- 0.1 for
      cortical bone tissue. The ratio of levofloxacin concentration in synovial tissue
      and plasma (synovial tissue/plasma) was 1.2 +/- 0.4. CONCLUSIONS: The
      concentrations of levofloxacin achieved in cancellous and cortical bone tissue
      and in synovial tissue are greater than the breakpoint for susceptible organisms,
      which is < or =2 mg/L.

PMID- 14963067
TI  - False-positive extended-spectrum beta-lactamase tests for Klebsiella oxytoca
      strains hyperproducing K1 beta-lactamase.

PMID- 14963068
TI  - Macrolide resistance and genotypic characterization of Streptococcus pneumoniae
      in Asian countries: a study of the Asian Network for Surveillance of Resistant
      Pathogens (ANSORP).
AB  - OBJECTIVES: To characterize mechanisms of macrolide resistance among
      Streptococcus pneumoniae from 10 Asian countries during 1998-2001. METHODS:
      Phenotypic and genotypic characterization of the isolates and their resistance
      mechanisms. RESULTS: Of 555 isolates studied, 216 (38.9%) were susceptible, 10
      (1.8%) were intermediate and 329 (59.3%) were resistant to erythromycin. Vietnam
      had the highest prevalence of erythromycin resistance (88.3%), followed by Taiwan
      (87.2%), Korea (85.1%), Hong Kong (76.5%) and China (75.6%). Ribosomal
      methylation encoded by erm(B) was the most common mechanism of erythromycin
      resistance in China, Taiwan, Sri Lanka and Korea. In Hong Kong, Singapore,
      Thailand and Malaysia, efflux encoded by mef(A) was the more common in
      erythromycin-resistant isolates. In most Asian countries except Hong Kong,
      Malaysia and Singapore, erm(B) was found in >50% of pneumococcal isolates either
      alone or in combination with mef(A). The level of erythromycin resistance among
      pneumococcal isolates in most Asian countries except Thailand and India was very
      high with MIC(90)s of >128 mg/L. Molecular epidemiological studies suggest the
      horizontal transfer of the erm(B) gene and clonal dissemination of resistant
      strains in the Asian region. CONCLUSION: Data confirm that macrolide resistance
      in pneumococci is a serious problem in many Asian countries.

PMID- 14963069
TI  - Mutant prevention concentration: comparison of fluoroquinolones and linezolid
      with Mycobacterium tuberculosis.
AB  - OBJECTIVES: The mutant prevention concentration (MPC) has recently been defined
      to characterize the capacity for severely restricting the selection of resistant
      mutants during antibiotic treatment. We determined this parameter for
      ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin and linezolid in
      Mycobacterium tuberculosis clinical isolates in our setting. METHODS: We
      determined the antibiotic concentration that prevents the selection of resistant
      mutants following inoculation with a high mycobacteria inoculum on Middlebrook
      7H11 plates with serial dilutions of the antibiotics in 224 M. tuberculosis
      isolates. RESULTS: Fifty percent of the strains exhibited values of MPC (MPC(50))
      lower than 0.8, 0.6, 0.4, 0.4 and 0.6 mg/L for ciprofloxacin, levofloxacin,
      gatifloxacin, moxifloxacin and linezolid, respectively. If 90% of the strains are
      considered (MPC(90)), the values are seen to rise to 2, 1.8, 1, 1.2 and 1.2 mg/L,
      respectively. CONCLUSIONS: When we compare this parameter with the drug levels in
      serum and tissue, it can be seen that ciprofloxacin is the least useful of the
      fluoroquinolones studied, whereas moxifloxacin appears to be the most active.
      Linezolid exhibits excellent activity against this microorganism (MPC(90) 1.2
      mg/L and AUC 140.3 mg.h/L) and this makes us consider that its usefulness in the
      treatment of this pathology should be thoroughly evaluated.

PMID- 14963070
TI  - Immunosuppressive drugs as an adjuvant to HIV treatment.
AB  - Although highly active antiretroviral therapy (HAART) has dramatically changed
      the epidemiological impact of HIV infection, many problems with currently used
      antiretroviral therapy have underscored the urgent need for additional
      therapeutic approaches. Structured treatment interruption trials, which can be
      considered an immune-based therapy with an autologous virus, have failed to
      control viral replication in most chronically HIV-1-infected patients.
      Alternative approaches could be the use of immunosuppressive drugs to enhance the
      control of viral replication mediated by their immune and antiviral properties.
      The use of immunosuppressive drugs may reduce the number of activated CD4 cells
      that support massive virus production and may prevent sequestration of CD4 T
      cells into lymphoid tissue, which is the place of antigen presentation and
      productive HIV infection. The strategy of using drugs that interfere with the HIV
      life-cycle, acting on the target cells of HIV rather than on viral enzymes,
      offers the advantage of avoiding the development of antiretroviral drug-resistant
      HIV mutants. However, it is not known if these approaches will clinically benefit
      long-term infection, by establishing a new immunological set-point that may
      affect the rate of disease progression. Caution is required when using HAART in
      combination with cytostatic drugs in HIV-1 infection until their impact and long
      term safety have been investigated further in larger clinical trials.

PMID- 14963071
TI  - Implications of finding synergic in vitro drug-drug interactions between
      interferon-alpha and ribavirin for the treatment of hepatitis C virus.
AB  - Hepatitis C virus (HCV) infections are currently treated using a combination of
      interferon-alpha (IFN-alpha) and ribavirin (RBV). If IFN-alpha is utilized alone,
      the sustained virological response (SVR) rate is approximately 20%, whereas when
      RBV is used alone it does not lead to an SVR. However, when IFN-alpha and RBV are
      used together, the combination leads to an SVR rate of approximately 40%. This
      clinical synergy is thought to be due to the direct antiviral effects of RBV, or
      to indirect effects of RBV that stimulate the immune response. Evidence for
      either hypothesis is limited. Recently, we undertook an in vitro drug-drug
      combination analysis using surrogate model systems of HCV replication and found a
      reproducible synergy of antiviral effects between the two drugs at
      physiologically relevant drug concentrations. Our findings provide experimental
      support for the contention that the direct effects of these drugs' antiviral
      activity are responsible for the clinical synergy observed in patients.

PMID- 14963072
TI  - Increase in the rate of nosocomial Clostridium difficile-associated diarrhoea
      during shortages of piperacillin-tazobactam and piperacillin.

PMID- 14963073
TI  - Risk management in obstetric care for family physicians: results of a 10-year
      project.
AB  - BACKGROUND: Malpractice issues within the United States remain a critical factor
      for family physicians providing obstetric care. Although tort reform is being
      widely discussed, little has been written regarding the malpractice crisis from a
      risk management perspective. METHODS: Between 1989 and 1998, a 10-year risk
      management study at the UC Davis Health System provided a unique collaboration
      between researchers, a mutual insurance carrier and family physicians practicing
      obstetrics. Physicians were asked to comply with standardized clinical
      guidelines, attend continuing medical education (CME) seminars, and submit
      obstetric medical records for review. Feedback analysis was provided to each
      physician on their records, and the insurance carrier tracked interim malpractice
      claims. RESULTS: One hundred and ninety-four physicians participated, attending
      to 32,831 births. Compliance with project guidelines was 91%. Five closed
      obstetric cases were reported with only one settlement reported to the National
      Provider Data Bank. Physicians believed the project was beneficial to their
      practices. CONCLUSIONS: Family physicians practicing obstetrics are willing to
      participate in a collaborative risk management program and are compliant with
      standardized clinical guidelines. The monetary award for successful malpractice
      claims was relatively low. This collaborative risk management model may offer a
      potential solution to the current malpractice crisis.

PMID- 14963074
TI  - Predictors of incomplete flexible sigmoidoscopy.
AB  - OBJECTIVES: Flexible sigmoidoscopy (flex sig) is an easily administered method of
      screening for colorectal polyps and cancer. In some patients, the depth of
      insertion is incomplete, which may result in missed polyps and cancers. To
      address the question of prospective patient selection for this procedure, we
      analyzed the factors affecting depth of insertion of sigmoidoscopies performed in
      outpatients over a 3-year period. STUDY DESIGN: The study involved retrospective
      chart review of procedures performed by one endoscopist over a 3-year period.
      OUTCOMES MEASURED: Variables that might affect the extent of depth of insertion
      of the flexible sigmoidoscope. RESULTS: We developed separate logistic regression
      models of incomplete depth of insertion for women and men because sex was an
      effect modifier for many factors. For women, incomplete depth of insertion was
      related to inadequate preparation [odds ratio (OR) 3.59; 95% confidence interval
      (CI), 1.66 to 7.78]. Comparisons were made with the lowest risk group-women
      younger than 70 years with no hysterectomy. For women younger than 70 years,
      those with a hysterectomy were more likely to have an incomplete examination (OR
      6.89; 95% CI, 2.68 to 17.73). For women 70 years and older, the odds ratio for
      women with a hysterectomy (OR 2.68; 95% CI, 0.96 to 7.46) was similar to that of
      women without a hysterectomy (OR 4.79; 95% CI, 2.27 to 10.12). For men,
      incomplete depth of insertion was related to age older than 75 years (OR 6.51;
      95% CI, 1.72 to 30.40), history of abdominal surgery (OR 3.15; 95% CI, 0.95 to
      10.41), and weight loss (OR 9.62; 95% CI, 1.98 to 46.67). CONCLUSIONS: Our study
      showed a relationship between incomplete examination and increasing age, female
      sex (more than 75% of the incomplete examinations were in women), poor bowel
      preparation (in women), hysterectomy, abdominal surgery (in men) and weight loss
      (in men). Further research is necessary to determine whether a predictive model
      can be developed that would be useful to select patients most appropriate for
      flex sig. In those patients in whom difficulty is anticipated, the choice can be
      made in to perform flex sig under sedation, analgesia, with the help of
      distraction techniques, or offer primary colonoscopy.

PMID- 14963075
TI  - The communication patterns of internal medicine and family practice physicians.
AB  - BACKGROUND: Although differences between Internal Medicine (IM) and Family
      Practice (FP) physicians have been examined in terms of care outcomes and cost,
      there have been few studies of specialty differences in physician-patient
      communication. METHODS: In 1995, 277 clinical encounters with 29 full-time,
      community-based FP physicians and 287 clinical encounters with 30 full-time,
      community based IM physicians were audiotaped. Communication was evaluated with
      the Roter Interaction Analysis System to reflect data gathering, patient
      education and counseling, rapport building, partnership building, verbal
      dominance, and patient-centeredness. Patient satisfaction was measured with an
      exit questionnaire. RESULTS: IM clinicians ask more biomedical questions (P
      =.02). FP clinicians engage in more psychosocial discussion (P =.02) and tend to
      engage in more emotionally supportive exchanges such as empathy and reassurance
      (P =.06). Significant interaction effects show differential treatment of patient
      subgroups by specialty; FP physicians were more verbally dominant with female
      patients (P <.01) and more patient-centered in their communication style with
      minority patients (P =.03). Although patient satisfaction was similar for IM and
      FP, satisfaction was more closely linked to measures of rapport and patient
      centeredness for patients of FP physicians than for patients of internists.
      CONCLUSIONS: The current work adds insight into FP and IM differences in both
      physician-patient communication and predictors of patient satisfaction.

PMID- 14963076
TI  - Patient self-referral for radiologic screening tests: clinical and ethical
      concerns.
AB  - Retail marketing of radiologic screening tests is increasingly common in the
      United States. Without a physician referral, patients can now directly purchase
      screening computed tomography (CT) or ultrasound scans. In this article, we
      consider the clinical and ethical ramifications of widespread screening of low
      risk populations with 4 commonly marketed tests: whole-body CT, CT-based heart
      scans, heel ultrasound for osteoporosis, and carotid duplex sonography for
      carotid stenosis. All the tests are too inaccurate for screening in low-risk
      populations, and none has been proven to lead to early, beneficial intervention.
      Screening could be harmful if false-positive tests lead to extensive or invasive
      diagnostic evaluation. Finally, widespread testing could increase health care
      costs with little public health benefit. Patients should probably avoid
      radiologic screening tests until the tests have been appropriately evaluated in
      controlled studies and recommended by unbiased national panels, such as the
      United States Preventive Services Task Force. Primary care physicians and their
      professional societies should emphasize the uncertain benefits and potential
      hazards of indiscriminate imaging among healthy, asymptomatic consumers.

PMID- 14963077
TI  - Factors related to the choice of family medicine: a reassessment and literature
      review.
AB  - BACKGROUND: Recent decreases in the number of students entering family medicine
      has prompted reconsideration of what is known about the factors affecting
      specialty choice. METHODS: Thirty-six articles on family medicine specialty
      choice published since 1993 were reviewed and rated for quality. RESULTS: Rural
      background related positively and parents' socioeconomic status relates
      negatively to choice of family medicine. Career intentions at entry to medical
      school predict specialty choice. Students who believe primary care is important,
      have low income expectations, and do not plan a research career are more likely
      to choose family medicine. The school characteristic related to choice of family
      medicine is public ownership. Large programs to increase numbers entering primary
      care seem effective. Required family medicine time in clinical years is related
      to higher numbers selecting family medicine. Faculty role models serve both as
      positive and negative influences. Students rejecting family medicine are
      concerned about prestige, low income, and breadth of knowledge required. Students
      planning on a career in a disadvantaged or rural area are more likely to enter
      family medicine. CONCLUSIONS: Multiple factors are consistently shown to be
      related to the choice of the specialty of family medicine.

PMID- 14963078
TI  - Direct-to-consumer advertising: physicians' views of its effects on quality of
      care and the doctor-patient relationship.
AB  - BACKGROUND: The objective of the study was to determine physicians' views of the
      effects of Direct-to-Consumer Advertising (DTCA) on health service utilization,
      quality of care, and the doctor-patient relationship. METHODS: Cross-sectional
      survey of a nationally representative sample of US physicians to determine their
      perceptions of the effects of patients discussing information from DTCA on time
      efficiency; requests for specific interventions; health outcomes; and the doctor
      patient relationship. RESULTS: Physicians reported that more than half (56%) of
      patients who discussed information from DTCA in a visit did so because they
      wanted a specific intervention, such as a test, change in medication, or
      specialist referral. The physician deemed 49% of these requests clinically
      inappropriate. Physicians filled 69% of requests they deemed clinically
      inappropriate; 39% of physicians perceived DTCA as damaging to the time
      efficiency of the visit, and 13% saw it as helpful. Thirty-three percent of
      physicians thought discussing DTCA had improved the doctor-patient relationship;
      8% felt it had worsened it. The effect on the relationship was strongly
      associated with doing what the patient wanted. CONCLUSIONS: DTCA can have good
      and bad effects on quality of care, the doctor-patient relationship, and health
      service utilization. The benefits might be maximized, and the harms minimized, by
      increasing the accuracy of information in advertisements; enhancing physicians'
      communication and negotiation skills; and encouraging patients to respect
      physicians' clinical expertise.

PMID- 14963079
TI  - Screening for intimate partner violence in a primary care setting: the validity
      of "feeling safe at home" and prevalence results.
AB  - BACKGROUND: We conducted a study to assess the validity of a screening question
      commonly used to detect intimate partner violence (IPV) in primary care settings.
      We also analyzed prevalence and risk factors of IPV. METHODS: We used an embedded
      domestic violence detection instrument in a general health questionnaire at one
      family medicine clinic. Questionnaire scales included a modified version of the
      Conflict Tactics Scale (CTS), depression and alcohol use scales, and a personal
      safety question ("Do you feel safe at home?"). We assessed the sensitivity,
      specificity, and predictive value of the personal safety question in our sample
      using responses to the modified CTS and the personal safety question. Three
      hundred ninety-nine female patients over the age of 18 completed the survey.
      RESULTS: CTS results revealed 44.3% of women experienced any violence, 43.5% of
      women experienced psychological violence in the presence or absence of physical
      violence, and 10.3% experienced physical violence in the presence or absence of
      psychological violence in the previous 90 days. The sensitivity of a single
      question used to detect any violence ("Do you feel safe at home?") was 8.8%; the
      specificity was 91.2%. Racial identity, marital status, and depression influenced
      the likelihood of IPV. CONCLUSIONS: These preliminary results call into question
      the utility of the safety question "Do you feel safe at home" for detecting cases
      of intimate partner violence in a primary care sample.

PMID- 14963080
TI  - Carpal tunnel syndrome as an occupational disease.
AB  - BACKGROUND: Symptoms related to carpal tunnel syndrome (CTS) represent common
      patient complaints for many primary care physicians. However, there is a
      surprising lack of guidelines on diagnosing occupational CTS readily accessible
      to primary care physicians. This article aims to fill part of that void by
      reviewing historical aspects of occupational CTS, leading up to more current
      epidemiologic studies of the association of CTS with occupational ergonomic risk
      factors. METHODS: The English medical literature was reviewed on the relationship
      between CTS and occupational ergonomic risk factors. Recent legislative
      initiatives are discussed. Guidelines of diagnosing and managing occupational CTS
      are outlined. RESULTS: Many studies are divided regarding whether CTS is
      associated with highly repetitive/forceful/vibration work. However, a subset of
      patients presenting with symptoms related to CTS probably has occupational CTS.
      These patients can be objectively diagnosed and successfully treated and are able
      to return to work. CONCLUSIONS: By being armed with knowledge regarding the
      background of CTS and by following simple diagnosis and treatment guidelines, the
      family practitioner should be able to manage many patients presenting with work
      related CTS.

PMID- 14963081
TI  - Vasa previa diagnosis and management.
AB  - INTRODUCTION: Vasa previa is an uncommon obstetrical complication that poses a
      high risk of fetal demise if not recognized before rupture of membranes. It is
      vital that providers recognize risk factors for vasa previa and diagnose this
      condition before the onset of labor so that fetal shock or demise is prevented.
      METHODS: We report a patient with a bilobed placenta and perinatal hemorrhage
      caused by vasa previa that was not detected with antepartum ultrasound. A review
      of the literature published between January 1965 and August 2002 was conducted
      using a MEDLINE-assisted search using the key words "vasa previa," "bilobed
      placenta," and "succenturiate." RESULTS: Risk factors for vasa previa have been
      identified. Advances in ultrasound have led to improved ability to diagnose this
      condition. Evaluation of patients in high-risk groups with transvaginal color
      flow Doppler ultrasound should be considered. The accuracy of this technique for
      diagnosing vasa previa is not known, nor is the true incidence of this condition.
      Antepartum diagnosis is associated with improved outcomes but does not eliminate
      morbidity and mortality. CONCLUSIONS: A high index of suspicion for vasa previa
      at the time of amniotomy is required, because all cases cannot be diagnosed
      before the onset of labor.

PMID- 14963082
TI  - Recombinant factor VIIa for uncontrolled bleeding in 2 different cases of
      coagulopathy.

PMID- 14963083
TI  - A poor outcome after inappropriate use of an over-the-counter fetal listening
      device.

PMID- 14963084
TI  - Wegener granulomatosis: case report and brief literature review.

PMID- 14963085
TI  - "I can't move".

PMID- 14963086
TI  - JABFP listens and sets research agenda.

PMID- 14963087
TI  - Hysteria revisited.

PMID- 14963088
TI  - Family practice OB: to be or not to be? Liability is the question.

PMID- 14963089
TI  - Intracellular spheroid bodies of Rhopalodia gibba have nitrogen-fixing apparatus
      of cyanobacterial origin.
AB  - Nitrogen fixation is not regarded as a eukaryotic invention. The process has only
      been reported as being carried out by bacteria. These prokaryotes typically
      interact with their eukaryotic hosts as extracellular and temporary nonobligate
      nitrogen-fixing symbionts. However, intracellular permanent "spheroid bodies"
      have been reported within the fresh-water diatom Rhopalodia gibba, and these,
      too, have been speculated as being able to provide nitrogen to their host diatom.
      These spheroid bodies have gram-negative characteristics with thylakoids. We
      demonstrate that they fix nitrogen under light conditions. We also show that
      phylogenetic analyses of their 16rRNA and nif D genes predict that their genome
      is closely related to that of Cyanothece sp. ATCC 51.142, a free-living
      diazotrophic cyanobacterium. We suggest that the intracellular spheroid bodies of
      Rhopalodia gibba may represent a vertically transmitted, permanent endosymbiotic
      stage in the transition from a free-living diazotrophic cyanobacterium to a
      nitrogen-fixing eukaryotic organelle.

PMID- 14963090
TI  - Evidence of positively selected sites in mammalian alpha-defensins.
AB  - Alpha-defensins are a family of mammalian antimicrobial peptides that exhibit
      variable activity against a panel of microbes, including bacteria, fungi, and
      enveloped viruses. We have employed a maximum-likelihood approach to detect
      evidence of positive selection (adaptive evolution) in the evolution of these
      important molecules of the innate immune response. We have identified 14 amino
      acid sites that are predicted to be subject to positive selection. Furthermore,
      we show that all these sites are located in the mature antimicrobial peptide and
      not in the prepropeptide region of the molecule, implying that they are of
      functional importance. These results suggest that mammalian alpha-defensins have
      been under selective pressure to evolve in response to potentially infectious
      challenges by fast-evolving microbes.

PMID- 14963091
TI  - Evidence for a complex demographic history of chimpanzees.
AB  - To characterize patterns of genomic variation in central chimpanzees (Pan
      troglodytes troglodytes) and gain insight into their evolution, we sequenced nine
      unlinked, intergenic regions, representing a total of 19,000 base pairs, in 14
      individuals. When these DNA sequences are compared with homologous sequences
      previously collected in humans and in western chimpanzees (Pan troglodytes
      verus), nucleotide diversity is higher in central chimpanzees than in western
      chimpanzees or in humans. Consistent with a larger effective population size of
      central chimpanzees, levels of linkage disequilibrium are lower than in humans.
      Patterns of linkage disequilibrium further suggest that homologous gene
      conversion may be an important contributor to genetic exchange at short
      distances, in agreement with a previous study of the same DNA sequences in
      humans. In central chimpanzees, but not in western chimpanzees, the allele
      frequency spectrum is significantly skewed towards rare alleles, pointing to
      population size changes or fine-scale population structure. Strikingly, the
      extent of genetic differentiation between western and central chimpanzees is much
      stronger than what is seen between human populations. This suggests that careful
      attention should be paid to geographic sampling in studies of chimpanzee genetic
      variation.

PMID- 14963092
TI  - Phylogenetic analysis of the vertebrate galectin family.
AB  - Galectins form a family of structurally related carbohydrate binding proteins
      (lectins) that have been identified in a large variety of metazoan phyla. They
      are involved in many biological processes such as morphogenesis, control of cell
      death, immunological response, and cancer. To elucidate the evolutionary history
      of galectins and galectin-like proteins in chordates, we have exploited three
      independent lines of evidence: (i) location of galectin encoding genes (LGALS) in
      the human genome; (ii) exon-intron organization of galectin encoding genes; and
      (iii) sequence comparison of carbohydrate recognition domains (CRDs) of chordate
      galectins. Our results suggest that a duplication of a mono-CRD galectin gene
      gave rise to an original bi-CRD galectin gene, before or early in chordate
      evolution. The N-terminal and C-terminal CRDs of this original galectin
      subsequently diverged into two different subtypes, defined by exon-intron
      structure (F4-CRD and F3-CRD). We show that all vertebrate mono-CRD galectins
      known to date belong to either the F3- or F4- subtype. A sequence of duplication
      and divergence events of the different galectins in chordates is proposed.

PMID- 14963093
TI  - Phylogeny and comparative substitution rates of frogs inferred from sequences of
      three nuclear genes.
AB  - Phylogenetic relationships among major clades of anuran amphibians were studied
      using partial sequences of three nuclear protein coding genes, Rag-1, Rag-2, and
      rhodopsin in 26 frog species from 18 families. The concatenated nuclear data set
      comprised 2,616 nucleotides and was complemented by sequences of the
      mitochondrial 12S and 16S rRNA genes for analyses of evolutionary rates. Separate
      and combined analyses of the nuclear markers supported the monophyly of modern
      frogs (Neobatrachia), whereas they did not provide support for the monophyly of
      archaic frog lineages (Archaeobatrachia), contrary to previous studies based on
      mitochondrial data. The Neobatrachia contain two well supported clades that
      correspond to the subfamilies Ranoidea (Hyperoliidae, Mantellidae, Microhylidae,
      Ranidae, and Rhacophoridae) and Hyloidea (Bufonidae, Hylidae, Leptodactylidae,
      and Pseudidae). Two other families (Heleophrynidae and Sooglossidae) occupied
      basal positions and probably represent ancient relicts within the Neobatrachia,
      which had been less clearly indicated by previous mitochondrial analyses. Branch
      lengths of archaeobatrachians were consistently shorter in all separate analyses,
      and nonparametric rate smoothing indicated accelerated substitution rates in
      neobatrachians. However, relative rate tests confirmed this tendency only for
      mitochondrial genes. In contrast, nuclear gene sequences from our study and from
      an additional GenBank survey showed no clear phylogenetic trends in terms of
      differences in rates of molecular evolution. Maximum likelihood trees based on
      Rag-1 and using only one neobatrachian and one archaeobatrachian sequence,
      respectively, even had longer archaeobatrachian branches averaged over all
      pairwise comparisons. More data are necessary to understand the significance of a
      possibly general assignation of short branches to basal and species-poor taxa by
      tree-reconstruction algorithms.

PMID- 14963094
TI  - Positive selection at reproductive ADAM genes with potential intercellular
      binding activity.
AB  - Many genes with a role in reproduction, including those implicated in
      fertilization and spermatogenesis, have been shown to evolve at a faster rate
      relative to genes associated with other functions and tissues. These survey
      studies usually group a wide variety of genes with different characteristics and
      evolutionary histories as reproductive genes based on their site of expression or
      function. We have examined the molecular evolution of the ADAM (a disintegrin and
      metalloprotease) gene family, a structurally and functionally diverse group of
      genes expressed in reproductive and somatic tissue to test whether a variety of
      protein characteristics such as phylogenetic clusters, tissue of expression, and
      proteolytic and adhesive function can group fast evolving ADAM genes. We found
      that all genes were evolving under purifying selection (d(N)/d(S) < 1), although
      reproductive ADAMs, including those implicated in fertilization and
      spermatogenesis, evolved at the fastest rate. Genes with a role in binding to
      cell receptors in endogenous tissue appear to be evolving under purifying
      selection, regardless of the tissue of expression. In contrast, positive
      selection of codon sites in the disintegrin/cysteine-rich adhesion domains was
      detected exclusively in ADAMs 2 and 32, two genes expressed in the testis with a
      potential role in sperm-egg adhesion. Positive selection was detected in the
      transmembrane/cytosolic tail region of ADAM genes expressed in a variety of
      tissues.

PMID- 14963095
TI  - GFP-like proteins as ubiquitous metazoan superfamily: evolution of functional
      features and structural complexity.
AB  - Homologs of the green fluorescent protein (GFP), including the recently described
      GFP-like domains of certain extracellular matrix proteins in Bilaterian
      organisms, are remarkably similar at the protein structure level, yet they often
      perform totally unrelated functions, thereby warranting recognition as a
      superfamily. Here we describe diverse GFP-like proteins from previously
      undersampled and completely new sources, including hydromedusae and planktonic
      Copepoda. In hydromedusae, yellow and nonfluorescent purple proteins were found
      in addition to greens. Notably, the new yellow protein seems to follow exactly
      the same structural solution to achieving the yellow color of fluorescence as
      YFP, an engineered yellow-emitting mutant variant of GFP. The addition of these
      new sequences made it possible to resolve deep-level phylogenetic relationships
      within the superfamily. Fluorescence (most likely green) must have already
      existed in the common ancestor of Cnidaria and Bilateria, and therefore GFP-like
      proteins may be responsible for fluorescence and/or coloration in virtually any
      animal. At least 15 color diversification events can be inferred following the
      maximum parsimony principle in Cnidaria. Origination of red fluorescence and
      nonfluorescent purple-blue colors on several independent occasions provides a
      remarkable example of convergent evolution of complex features at the molecular
      level.

PMID- 14963096
TI  - The mitochondrial genome of the house centipede scutigera and the monophyly
      versus paraphyly of myriapods.
AB  - Recent advances in molecular phylogenetics are continuously changing our
      perception of the phylogenetic relationships among the main arthropod lineages:
      crustaceans, hexapods, chelicerates, and myriapods. Besides the intrinsic
      interest in unraveling the evolution of the largest animal phylum, these studies
      are basic to an understanding of one of the major transitions in animal evolution
      i.e., the conquest of land with all its associated structural and functional
      adaptations. Myriapods have been traditionally considered the closest relatives
      of hexapods, thus implying only one origin of terrestriality for the tracheate
      lineage, but this view is now challenged by molecular evidence. Sequence data
      available to date for centipedes and millipedes are very limited, and the taxon
      sampling is strongly biased. The most critical gap was the scutigeromorph
      centipedes, which are the sister group to all remaining Chilopoda from which they
      probably diverged in the Silurian if not earlier. We obtained the first complete
      mitochondrial sequence for a representative of this clade, the house centipede.
      In our phylogenetic analyses of the protein-coding genes in this mitochondrial
      genome, along with 16 further ones representing the other major arthropod clades
      plus two outgroups, the myriapods formed a clade with the chelicerates. This
      implies that water-to-land transition occurred at least three times (hexapods,
      myriapods, arachnids) during the evolution of the Arthropoda. In addition, in
      contrast to all previous studies, our best supported topologies favor paraphyly
      of the myriapods with respect to the chelicerates. This would increase to four
      the main events of land colonization in arthropods (once for centipedes, once for
      millipedes).

PMID- 14963097
TI  - Origins, lineage-specific expansions, and multiple losses of tyrosine kinases in
      eukaryotes.
AB  - Tyrosine kinases are important components of metazoan signaling pathways, and
      their mutant forms are implicated in various malignancies. Searching the
      sequences from the genomes of 28 eukaryotes and the GenBank, we found tyrosine
      kinases not only in metazoans but also in the green algae Chlamydomonas
      reinhardtii, the potato late blight pathogen Phytophthora infestans, and the
      protozoan pathogen Entamoeba histolytica, contrary to the current view that
      tyrosine kinases are animal-specific. Based on a phylogenetic analysis, we
      divided this gene family into 43 subfamilies and found that at least 19 tyrosine
      kinases were likely present in the common ancestor of chordates, arthropods, and
      nematodes. Interestingly, most of the subfamilies have conserved domain
      organizations among subfamily members but have undergone different degrees of
      expansion during the evolution of metazoans. In particular, a large number of
      duplications occurred in the lineage leading to the common ancestor of Tagifugu
      and mammals after its split from the Ciona lineage about 450 to 550 MYA. The
      timing of expansion coincides with proposed large-scale duplication event in the
      chordate lineage. Furthermore, gene losses have occurred in most subfamilies.
      Interestingly, different subfamilies have similar net gain rates in the chordates
      studied. However, the tyrosine kinases in mouse and human or in fruit fly and
      mosquito mostly have a one-to-one relationship between species, indicating that
      static periods of 90 Myr or longer in tyrosine kinase evolution have followed
      large expansion events.

PMID- 14963098
TI  - Two patterns of genome organization in mammals: the chromosomal distribution of
      duplicate genes in human and mouse.
AB  - Gene duplication occurs repeatedly in the evolution of genomes, and the
      rearrangement of genomic segments has also occurred repeatedly over the evolution
      of eukaryotes. We studied the interaction of these two factors in mammalian
      evolution by comparing the chromosomal distribution of multigene families in
      human and mouse. In both species, gene families tended to be confined to a single
      chromosome to a greater extent than expected by chance. The average number of
      families shared between chromosomes was nearly 60% higher in mouse than in human,
      and human chromosomes rarely shared large numbers of gene families with more than
      one or two other chromosomes, whereas mouse chromosomes frequently did so. A
      higher proportion of duplicate gene pairs on the same chromosome originated from
      recent duplications in human than in mouse, whereas a higher proportion of
      duplicate gene pairs on separate chromosomes arose from ancient duplications in
      human than in mouse. These observations are most easily explained by the
      hypotheses that (1) most gene duplications arise in tandem and are subsequently
      separated by segmental rearrangement events, and (2) that the process of
      segmental rearrangement has occurred at a higher rate in the lineage of mouse
      than in that of human.

PMID- 14963099
TI  - A molecular timeline for the origin of photosynthetic eukaryotes.
AB  - The appearance of photosynthetic eukaryotes (algae and plants) dramatically
      altered the Earth's ecosystem, making possible all vertebrate life on land,
      including humans. Dating algal origin is, however, frustrated by a meager fossil
      record. We generated a plastid multi-gene phylogeny with Bayesian inference and
      then used maximum likelihood molecular clock methods to estimate algal divergence
      times. The plastid tree was used as a surrogate for algal host evolution because
      of recent phylogenetic evidence supporting the vertical ancestry of the plastid
      in the red, green, and glaucophyte algae. Nodes in the plastid tree were
      constrained with six reliable fossil dates and a maximum age of 3,500 MYA based
      on the earliest known eubacterial fossil. Our analyses support an ancient (late
      Paleoproterozoic) origin of photosynthetic eukaryotes with the primary
      endosymbiosis that gave rise to the first alga having occurred after the split of
      the Plantae (i.e., red, green, and glaucophyte algae plus land plants) from the
      opisthokonts sometime before 1,558 MYA. The split of the red and green algae is
      calculated to have occurred about 1,500 MYA, and the putative single red algal
      secondary endosymbiosis that gave rise to the plastid in the cryptophyte,
      haptophyte, and stramenopile algae (chromists) occurred about 1,300 MYA. These
      dates, which are consistent with fossil evidence for putative marine algae (i.e.,
      acritarchs) from the early Mesoproterozoic (1,500 MYA) and with a major
      eukaryotic diversification in the very late Mesoproterozoic and Neoproterozoic,
      provide a molecular timeline for understanding algal evolution.

PMID- 14963100
TI  - Genetic diversity patterns in the SR-BI/II locus can be explained by a recent
      selective sweep.
AB  - The human scavenger receptor class B type I (SR-BI and splice variant SR-BII)
      plays a central role in HDL cholesterol metabolism and represents a candidate
      gene for a number of related diseases. We examined the genetic diversity of its
      coding and flanking regions in a sample of 178 chromosomes from individuals of
      European, African, East Asian (including Southeast Asian), Middle-Eastern as well
      as Amerindian descent. Nine of the 14 polymorphisms observed are new. Four of the
      five variants causing amino acid replacements, G2S, S229G, R484W, and G499R, are
      likely to affect protein structure and function. SR-BI/BII diversity is
      partitioned among 19 haplotypes; all but one interconnected by single mutation or
      a recombination event. Such tight haplotype network and the unusual geographic
      partitioning of this diversity, high not only in Africa but in East Asia as well,
      suggests its recent origin and possible effect of selection. Coalescent analysis
      infers a relatively short time to the most recent common ancestor and points to
      population expansion in Africa and East Asia. These two continents differ
      significantly in pairwise F(ST) values, differing as well from a single cluster
      formed by Europe, Middle East and America. In the context of findings for
      similarly analyzed other loci, we propose that a selective sweep at the origin of
      modern human populations could explain the low level of ancestral SR-BI/II
      diversity. The unusually deep split between Africa and Asia, well beyond the
      Upper Paleolithic when inferred under neutrality, is consistent with subsequent
      geographical and demographic expansion favoring the accumulation of new variants,
      especially in groups characterized by large effective population sizes, such as
      Asians and Africans. The relevance of such partitioning of SR-BI/II diversity
      remains to be investigated in genetic epidemiological studies which can be guided
      by the present findings.

PMID- 14963101
TI  - Microsatellites within genes: structure, function, and evolution.
AB  - Recently, increasingly more microsatellites, or simple sequence repeats (SSRs)
      have been found and characterized within protein-coding genes and their
      untranslated regions (UTRs). These data provide useful information to study
      possible SSR functions. Here, we review SSR distributions within expressed
      sequence tags (ESTs) and genes including protein-coding, 3'-UTRs and 5'-UTRs, and
      introns; and discuss the consequences of SSR repeat-number changes in those
      regions of both prokaryotes and eukaryotes. Strong evidence shows that SSRs are
      nonrandomly distributed across protein-coding regions, UTRs, and introns.
      Substantial data indicates that SSR expansions and/or contractions in protein
      coding regions can lead to a gain or loss of gene function via frameshift
      mutation or expanded toxic mRNA. SSR variations in 5'-UTRs could regulate gene
      expression by affecting transcription and translation. The SSR expansions in the
      3'-UTRs cause transcription slippage and produce expanded mRNA, which can be
      accumulated as nuclear foci, and which can disrupt splicing and, possibly,
      disrupt other cellular function. Intronic SSRs can affect gene transcription,
      mRNA splicing, or export to cytoplasm. Triplet SSRs located in the UTRs or intron
      can also induce heterochromatin-mediated-like gene silencing. All these effects
      caused by SSR expansions or contractions within genes can eventually lead to
      phenotypic changes. SSRs within genes evolve through mutational processes similar
      to those for SSRs located in other genomic regions including replication
      slippage, point mutation, and recombination. These mutational processes generate
      DNA changes that should be connected by DNA mismatch repair (MMR) system.
      Mutation that has escaped from the MMR system correction would become new alleles
      at the SSR loci, and then regulate and/or change gene products, and eventually
      lead to phenotype changes. Therefore, SSRs within genes should be subjected to
      stronger selective pressure than other genomic regions because of their
      functional importance. These SSRs may provide a molecular basis for fast
      adaptation to environmental changes in both prokaryotes and eukaryotes.

PMID- 14963102
TI  - A new group of tyrosine recombinase-encoding retrotransposons.
AB  - A wide variety of novel tyrosine recombinase (YR)-encoding retrotransposons were
      identified using data emerging from the various eukaryotic genome sequencing
      projects. Although many of these elements are clearly members of the previously
      described DIRS group of YR retrotransposons, a substantial number, including
      elements from a variety of fungi and animals, belong to a distinct and previously
      unrecognized group. We refer to these latter elements as the Ngaro group after a
      representative from zebrafish. Like the members of the DIRS group, Ngaro elements
      encode proteins bearing reverse transcriptase (RT) and ribonuclease H (RH)
      domains similar to those of long terminal repeat (LTR) retrotransposons.
      Phylogenetic analyses based on alignments of RT/RH and YR domains, however,
      indicate that Ngaro and DIRS are anciently diverged groups. Differences in coding
      capacity also support the distinction between the two groups. For instance, we
      found that DIRS elements all encode a protein domain which is similar in sequence
      to the DNA methyltransferases of certain bacteriophages, whereas this domain is
      absent from all Ngaro elements. Together, the Ngaro and DIRS groups of YR
      retrotransposons contain elements with an astonishing diversity in structures,
      with variations in the nature of the associated repeat sequences and in the
      arrangement and complement of coding regions. In addition they contain elements
      with some surprising features, such as spliceosomal introns and long overlapping
      open reading frames.

PMID- 14963103
TI  - Adaptive evolution of sperm bindin tracks egg incompatibility in neotropical sea
      urchins of the genus Echinometra.
AB  - Bindin is a gamete recognition protein known to control species-specific sperm
      egg adhesion and membrane fusion in sea urchins. Previous analyses have shown
      that diversifying selection on bindin amino acid sequence is found when
      gametically incompatible species are compared, but not when species are
      compatible. The present study analyzes bindin polymorphism and divergence in the
      three closely related species of Echinometra in Central America: E. lucunter and
      E. viridis from the Caribbean, and E. vanbrunti from the eastern Pacific. The
      eggs of E. lucunter have evolved a strong block to fertilization by sperm of its
      neotropical congeners, whereas those of the other two species have not. As in the
      Indo-West Pacific (IWP) Echinometra, the neotropical species show high
      intraspecific bindin polymorphism in the same gene regions as in the IWP species.
      Maximum likelihood analysis shows that many of the polymorphic codon sites are
      under mild positive selection. Of the fixed amino acid replacements, most have
      accumulated along the bindin lineage of E. lucunter. We analyzed the data with
      maximum likelihood models of variation in positive selection across lineages and
      codon sites, and with models that consider sites and lineages simultaneously. Our
      results show that positive selection is concentrated along the E. lucunter bindin
      lineage, and that codon sites with amino acid replacements fixed in this species
      show by far the highest signal of positive selection. Lineage-specific positive
      selection paralleling egg incompatibility provides support that adaptive
      evolution of sperm proteins acts to maintain recognition of bindin by changing
      egg receptors. Because both egg incompatibility and bindin divergence are greater
      between allopatric species than between sympatric species, the hypothesis of
      selection against hybridization (reinforcement) cannot explain why adaptive
      evolution has been confined to a single lineage in the American Echinometra.
      Instead, processes acting to varying degrees within species (e.g., sperm
      competition, sexual selection, and sexual conflict) are more promising
      explanations for lineage-specific positive selection on bindin.

PMID- 14963104
TI  - Recombination drives the evolution of GC-content in the human genome.
AB  - Unraveling the evolutionary forces responsible for variations of neutral
      substitution patterns among taxa or along genomes is a major issue in the
      identification of functional sequence features. Mammalian genomes show large
      scale regional variations of GC-content (the isochores), but the substitution
      processes at the origin of this structure are poorly understood. We have analyzed
      the pattern of neutral substitutions in 14.3 Mb of primate noncoding regions. We
      show that the GC-content toward which sequences are evolving is strongly
      correlated (r(2) = 0.61, P </= 2 10(-16)) with the rate of crossovers (notably in
      females). This demonstrates that recombination drives the evolution of base
      composition in human (probably via the process of biased gene conversion). The
      present substitution patterns are very different from what they had been in the
      past, resulting in a major modification of the isochore structure of our genome.
      This non-equilibrium situation suggests that changes of recombination rates occur
      relatively frequently during evolution, possibly as a consequence of karyotype
      rearrangements. These results have important implications for understanding the
      spatial and temporal variations of substitution processes in a broad range of
      sexual organisms, and for detecting the hallmarks of natural selection in DNA
      sequences.

PMID- 14963105
TI  - Genetic evidence for the coexistence of pheromone perception and full
      trichromatic vision in howler monkeys.
AB  - Vertebrate pheromones are water-soluble chemicals perceived mainly by the
      vomeronasal organ (VNO) for intraspecific communications. Humans, apes, and Old
      World (OW) monkeys lack functional genes responsible for the pheromone signal
      transduction and are generally insensitive to vomeronasal pheromones. It has been
      hypothesized that the evolutionary deterioration of pheromone sensitivity
      occurred because pheromone communication became redundant after the emergence of
      full trichromatic color vision via the duplication of the X-chromosome-linked
      red/green opsin gene in the common ancestor of hominoids and OW monkeys.
      Interestingly, full trichromacy also evolved in the New World (NW) howler monkeys
      via an independent duplication of the same gene. Here we sequenced from three
      species of howler monkeys an essential component of the VNO pheromone
      transduction pathway, the gene encoding the ion channel TRP2. In contrast to
      those of hominoids and OW monkeys, the howler TRP2 sequences have none of the
      characteristics of pseudogenes. This and other observations indicate that howler
      monkeys have maintained both their systems of pheromone communication and full
      trichromatic vision, suggesting that the presence of full trichromacy alone does
      not lead to the loss of pheromone communication. We suggest that the ecological
      differences between OW and NW primates, particularly in habitat selection, may
      have also affected the evolution of pheromone perception.

PMID- 14963106
TI  - Molecular evolution of the phytochrome gene family in sorghum: changing rates of
      synonymous and replacement evolution.
AB  - The photoreceptor phytochromes, encoded by a small gene family, are responsible
      for controlling the expression of a number of light-responsive genes and
      photomorphogenic events, including agronomically important phenotypes such as
      flowering time and shade-avoidance behavior. The understanding and control of
      flowering time are particularly important goals in sorghum cultivar development
      for diverse environments, and naturally occurring variation in the phytochrome
      genes might prove useful in breeding programs. Also of interest is whether
      variation observed at the phytochrome loci in domesticated sorghum, or in
      particular races, is a result of human selection. Population genetic studies can
      reveal evidence of such selection in patterns of polymorphism and divergence. In
      this study we report a population genetic analysis of the PHY gene family in
      Sorghum bicolor (L.) Moench in a diverse panel including both cultivated and wild
      accessions. We show that the level of nucleotide variation in all gene family
      members is about half the average for this species, consistent with purifying
      selection acting on these loci. However, the rate of amino acid substitution is
      accelerated at PHYC compared to the other two loci. In comparisons to a closely
      related sorghum species, PHYC shows a pattern of intermediate frequency amino
      acid changes that differ from the patterns observed in comparisons across longer
      evolutionary distances. There is also a departure from expected patterns of
      polymorphism and divergence at synonymous sites in PHYC, although the data do not
      fit a simple model of directional or diversifying selection. Cultivated sorghum
      has a level of variation similar to that of wild relatives (ssp.
      verticilliflorum), but many polymorphisms are subspecies-specific, including
      several amino acid variants.

PMID- 14963107
TI  - A test of neutrality and constant population size based on the mismatch
      distribution.
AB  - Several factors including demographic changes, selection, and recombination are
      known to affect the distribution of the number of pairwise differences between
      DNA sequences. The effects of each of these forces have previously been used to
      estimate population parameter values using various assumptions about other
      factors. In this article, we use the predictions of the mismatch distribution
      under a standard neutral equilibrium model to design a coalescent simulation
      based test and detect any deviation from this equilibrium. When reliable
      independent estimates are available for the intragenic recombination rate, this
      test can be used as a neutrality test or a population expansion test in actual
      studies, under reasonable assumptions.

PMID- 14963108
TI  - Characterization of the interactions of estrogen receptor and MNAR in the
      activation of cSrc.
AB  - In this study, we have evaluated the molecular mechanism of Src activation after
      its interaction with estrogen receptor alpha (ERalpha) and a newly identified
      scaffold protein, called MNAR (modulator of nongenomic activity of ER). Under
      basal condition, Src enzymatic activity is inhibited by intramolecular
      interactions. The enzyme can be activated by interaction between the SH2 domain
      of Src and phosphotyrosine-containing sequences and/or by interaction between the
      SH3 domain of Src and proteins containing PXXP motifs. Mutational analysis and
      functional evaluation of MNAR and the use of ERalpha and cSrc mutants revealed
      that MNAR interacts with Src's SH3 domain via its N-terminal PXXP motif. Mutation
      of this motif abolished both the MNAR-induced activation of Src and the
      stimulation of ER transcriptional activity. ER interacts with Src's SH2 domain
      using phosphotyrosine 537, and this complex was further stabilized by MNAR-ER
      interaction. Mapping studies reveal that both the A/B domain and Y537 of ERalpha
      are required for MNAR-induced activation of ER transcriptional activity. The
      region responsible for MNAR interaction with ER maps to two N-terminal LXXLL
      motifs of MNAR. Mutation of these motifs prevented ER-MNAR complex formation and
      eliminated activation of the Src/MAPK pathway. These data explicate how the
      coordinate interactions between MNAR, ER, and Src lead to Src activation. Our
      findings also demonstrate that MNAR is a scaffold protein that mediates ER-Src
      interaction and plays an important role in the integration of ER action in Src
      mediated signaling.

PMID- 14963109
TI  - Differential role of the loop region between helices H6 and H7 within the orphan
      nuclear receptors small heterodimer partner and DAX-1.
AB  - The orphan nuclear receptors small heterodimer partner (SHP) and dosage-sensitive
      sex-reversal adrenal hypoplasia congenital (AHC) critical region on the X
      chromosome gene 1 (DAX-1) contain extra amino acids between helices H6 and H7 of
      LBD, and here we investigated a possible role of these additional amino acids.
      Transient transfection assay demonstrated that, in contrast to wild type, in
      mutant SHP Delta128-139 deletion of 12 extra amino acids in H6-H7 failed to
      repress the transactivity of orphan nuclear receptors such as estrogen receptor
      related receptor-gamma, hepatocyte nuclear factor 4alpha, and constitutive
      androstane receptor. Interestingly, yeast two-hybrid and glutathione-S
      transferase pull-down assays demonstrated that wild-type and SHP Delta128-139
      have similar abilities to interact with estrogen receptor-related receptor-gamma,
      hepatocyte nuclear factor 4alpha, and constitutive androstane receptor.
      Unexpectedly, in wild-type DAX-1 and mutant DAX-1 Delta338-362, deletion of 25
      extra amino acids in H6-H7 had no significant difference in the interaction and
      repression of steroidogenic factor 1 transactivation. Mutant SHP that contains
      DAX-1 extra amino acids or polyalanine stretch in H6-H7 showed indistinguishable
      pattern of repression from wild-type SHP. Interestingly, the swapped SHP mutant
      with DAX-1 extra amino acids interacted with EID-1 (E1A-like inhibitor of
      differentiation 1), which is characterized as an SHP-interacting corepressor.
      However, interaction between SHP Delta128-139 and EID-1 was significantly
      diminished. Moreover, SHP-mediated repression of constitutive androstane receptor
      transactivation was significantly released by down-regulation of EID-1 expression
      with EID-1 small interfering RNA. The present study suggests that H6-H7 loop
      regions of SHP and DAX-1 play a different role in the repression of nuclear
      receptor transactivation.

PMID- 14963110
TI  - Identification of a functional vitamin D response element in the human insulin
      like growth factor binding protein-3 promoter.
AB  - 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] plays a critical role in maintaining
      calcium and phosphate homeostasis and bone formation but also exhibits
      antiproliferative activity on many cancer cells, including prostate cancer. We
      have shown that the antiproliferative actions of 1,25-(OH)2D3 in the LNCaP human
      prostate cancer cell line are mediated in part by induction of IGF binding
      protein-3 (IGFBP-3). The purpose of this study was to determine the molecular
      mechanism involved in 1,25-(OH)2D3 regulation of IGFBP-3 expression and to
      identify the putative vitamin D response element (VDRE) in the IGFBP-3 promoter.
      We cloned approximately 6 kb of the IGFBP-3 promoter sequence and demonstrated
      its responsiveness to 1,25-(OH)2D3 in transactivation assays. Computer analysis
      identified a putative VDRE between -3296/-3282 containing the direct repeat motif
      GGTTCA ccg GGTGCA that is 92% identical with the rat 24-hydroxylase distal VDRE.
      In EMSAs, the vitamin D receptor (VDR) showed strong binding to the putative
      IGFBP-3 VDRE in the presence of 1,25-(OH)2D3. Supershift assays confirmed the
      presence of VDR in the IGFBP-3 VDRE complex. Chromatin immunoprecipitation assay
      demonstrated that 1,25-(OH)2D3 recruited the VDR/retinoid X receptor heterodimer
      to the VDRE site in the natural IGFBP-3 promoter in intact cells. In
      transactivation assays, the putative VDRE coupled to a heterologous simian virus
      40 promoter construct was induced 2-fold by 1,25-(OH)2D3. Mutations in the VDRE
      resulted in a loss of inducibility confirming the critical hexameric sequence. In
      conclusion, we have identified a functional VDRE in the distal region of the
      human IGFBP-3 promoter. The induction of IGFBP-3 by 1,25-(OH)2D3 appears to be
      directly mediated via VDR interaction with this VDRE.

PMID- 14963111
TI  - Prolactin and transforming growth factor-beta signaling exert opposing effects on
      mammary gland morphogenesis, involution, and the Akt-forkhead pathway.
AB  - Both prolactin (PRL) and TGF-beta regulate cell survival in mammary epithelial
      cells, but their mechanisms of interactions are not known. In primary mammary
      epithelial cells and the HC11 mouse mammary epithelial cell line, PRL prevented
      TGF-beta-induced apoptosis, as measured by terminal deoxynucleotidyltransferase
      dUTP nick-end labeling staining and caspase-3 activation. This effect depended on
      phosphatidyl inositol triphosphate kinase (PI3K). PI3K activates a downstream
      serine/threonine kinase, Akt; therefore, we investigated the role of Akt in the
      interaction between PRL and TGF-beta signaling. Akt activity was inhibited by TGF
      beta over a 20- to 60-min time course. In TGF-beta-treated cells, PRL
      disinhibited Akt in a PI3K-dependent manner. Expression of dominant negative Akt
      blocked the protective effect of PRL in TGF-beta-induced apoptosis. Transgenic
      mice overexpressing a dominant-negative TGF-beta type II receptor (DNIIR) in the
      mammary epithelium undergo hyperplastic alveolar development, and this effect was
      PRL dependent. Involution in response to teat sealing was slowed by
      overexpression of DNIIR; furthermore, Akt and forkhead phosphorylation increased
      in the sealed mammary glands of DNIIR mice. Thus, Akt appears to be an essential
      component of the interaction between PRL and TGF-beta signaling in mammary
      epithelial cells both in vitro and in vivo.

PMID- 14963112
TI  - The human erythrocyte proteome: analysis by ion trap mass spectrometry.
AB  - This report describes an analysis of the red blood cell proteome by ion trap
      tandem mass spectrometry in line with liquid chromatography. Mature red blood
      cells lack all internal cell structures and consist of cytoplasm within a plasma
      membrane envelope. To maximize outcome, total red blood cell protein was divided
      into two fractions of membrane-associated proteins and cytoplasmic proteins. Both
      fractions were divided into subfractions, and proteins were identified in each
      fraction separately through tryptic digestion. Membrane protein digests were
      collected from externally exposed proteins, internally exposed proteins,
      "spectrin extract" mainly consisting of membrane skeleton proteins, and membrane
      proteins minus spectrin extract. Cytoplasmic proteins were divided into 21
      fractions based on molecular mass by size exclusion chromatography. The tryptic
      peptides were separated by reverse-phase high-performance liquid chromatography
      and identified by ion trap tandem mass spectrometry. A total of 181 unique
      protein sequences were identified: 91 in the membrane fractions and 91 in the
      cytoplasmic fractions. Glyceraldehyde-3-phosphate dehydrogenase was identified
      with high sequence coverage in both membrane and cytoplasmic fractions.
      Identified proteins include membrane skeletal proteins, metabolic enzymes,
      transporters and channel proteins, adhesion proteins, hemoglobins, cellular
      defense proteins, proteins of the ubiquitin-proteasome system, G-proteins of the
      Ras family, kinases, chaperone proteins, proteases, translation initiation
      factors, and others. In addition to the known proteins, there were 43 proteins
      whose identification was not determined.

PMID- 14963114
TI  - Underrepresentation of the 3' region of the capsid pregenomic RNA of duck
      hepatitis B virus.
AB  - The pregenomic RNA (pgRNA) of hepadnaviruses is packaged into capsids where it is
      reverse transcribed to yield mature DNA genomes. This report describes
      differences between the 3' region and other regions of the pgRNA isolated from
      capsids. Analysis of capsid pgRNA isolated by using an established method
      involving micrococcal nuclease treatment demonstrated reduced levels of the 3'
      region of the pgRNA compared to the 5' region. This underrepresentation of the 3'
      region was partly a result of microccocal nuclease digestion of the 3' region
      because isolation of capsid pgRNA by an alternative method that did not involve
      nuclease treatment led to a greater, but not complete, recovery of the 3' region.
      These results indicate that the 3' region of the capsid pgRNA is susceptible to
      micrococcal nuclease digestion during its isolation and that the 3' region can
      still be underrepresented when capsid pgRNA is isolated without nuclease
      digestion. Additional experiments show that the 3' ends of capsid pgRNA isolated
      by micrococcal nuclease treatment are heterogeneously dispersed from nucleotide
      2577 to the poly(A) tail. These data provide evidence that the 3' region of the
      capsid pgRNA has biochemical properties different from those of its 5' region.
      Possibly, the 3' region of the pgRNA is not packaged into the interior of the
      capsid but rather is associated with a part of the capsid where it is susceptible
      to microccocal nuclease digestion.

PMID- 14963113
TI  - Role of ICP0 in the strategy of conquest of the host cell by herpes simplex virus
      1.

PMID- 14963115
TI  - Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human
      immunodeficiency virus across multiple ethnicities.
AB  - Although there is increasing evidence that virus-specific cytotoxic-T-lymphocyte
      (CTL) responses play an important role in the control of human immunodeficiency
      virus (HIV) replication in vivo, only scarce CTL data are available for the
      ethnic populations currently most affected by the epidemic. In this study, we
      examined the CD8(+)-T-cell responses in African-American, Caucasian, Hispanic,
      and Caribbean populations in which clade B virus dominates and analyzed the
      potential factors influencing immune recognition. Total HIV-specific CD8(+)-T
      cell responses were determined by enzyme-linked immunospot assays in 150 HIV
      infected individuals by using a clade B consensus sequence peptide set spanning
      all HIV proteins. A total of 88% of the 410 tested peptides were recognized, and
      Nef- and Gag-specific responses dominated the total response for each ethnicity
      in terms of both breadth and magnitude. Three dominantly targeted regions within
      these proteins that were recognized by >90% of individuals in each ethnicity were
      identified. Overall, the total breadth and magnitude of CD8(+)-T-cell responses
      correlated with individuals' CD4 counts but not with viral loads. The frequency
      of recognition for each peptide was highly correlated with the relative
      conservation of the peptide sequence, the presence of predicted immunoproteasomal
      cleavage sites within the C-terminal half of the peptide, and a reduced frequency
      of amino acids that impair binding of optimal epitopes to the restricting class I
      molecules. The present study thus identifies factors that contribute to the
      immunogenicity of these highly targeted and relatively conserved sequences in HIV
      that may represent promising vaccine candidates for ethnically heterogeneous
      populations.

PMID- 14963116
TI  - Transforming growth factor beta enhances the glucocorticoid response of the mouse
      mammary tumor virus promoter through Smad and GA-binding proteins.
AB  - Tissue-specific transcription is advantageously investigated by using viral
      promoters, which are selected for compact regulatory elements. Mouse mammary
      tumor virus (MMTV) has adapted to specialized cell types and targets initially B
      lymphocytes. We previously showed that, in B-cell lines, glucocorticoid-induced
      MMTV transcription requires an ETS family factor, GA-binding protein (GABP),
      bound in tandem to the MMTV DNA next to the glucocorticoid receptor (GR). We now
      report that transforming growth factor beta (TGF-beta) superinduces this response
      up to 10-fold through binding of its effectors, Smads, between the GABP-binding
      motifs. The basal level was unaffected. The TGF-beta-glucocorticoid cooperation
      also depended on GR and GABP binding, was transferable to another promoter, and
      occurred both with transiently transfected and with integrated templates. Smad3
      associated in vitro with GR, with GABPalpha (via the MH2 domain), and with
      GABPbeta, Smad4 only with GABPalpha. Interactions of Smad3 with GABP (when
      coexpressed or endogenous to B cells) were shown by coprecipitation and by
      mammalian two-hybrid assay. This composite DNA element integrates three signaling
      pathways deriving from TGF-beta, glucocorticoid hormones, and a unique ETS
      factor, and may allow MMTV to exploit factors from the milk. It may as well
      indicate novel possibilities for cellular regulatory networks.

PMID- 14963117
TI  - Protection against mucosal simian immunodeficiency virus SIV(mac251) challenge by
      using replicating adenovirus-SIV multigene vaccine priming and subunit boosting.
AB  - Whereas several recent AIDS vaccine strategies have protected rhesus macaques
      against a pathogenic simian/human immunodeficiency virus (SHIV)(89.6P) challenge,
      similar approaches have provided only modest, transient reductions in viral
      burden after challenge with virulent, pathogenic SIV, which is more
      representative of HIV infection of people. We show here that priming with
      replicating adenovirus recombinants encoding SIV env/rev, gag, and/or nef genes,
      followed by boosting with SIV gp120 or an SIV polypeptide mimicking the CD4
      binding region of the envelope, protects rhesus macaques from intrarectal
      infection with the highly pathogenic SIV(mac251). Using trend analysis,
      significant reductions in acute-phase and set point viremia were correlated with
      anti-gp120 antibody and cellular immune responses, respectively. Within
      immunization groups exhibiting significant protection, a subset (39%) of macaques
      have exhibited either no viremia, cleared viremia, or controlled viremia at the
      threshold of detection, now more than 40 weeks postchallenge. This combination
      prime-boost strategy, utilizing replication competent adenovirus, is a promising
      alternative for HIV vaccine development.

PMID- 14963118
TI  - Specificity of interaction of INI1/hSNF5 with retroviral integrases and its
      functional significance.
AB  - Integrase interactor 1 (INI1)/hSNF5 is a host factor that directly interacts with
      human immunodeficiency virus type 1 (HIV-1) integrase and is incorporated into
      HIV-1 virions. Here, we show that while INI1/hSNF5 is completely absent from
      purified microvesicular fractions, it is specifically incorporated into HIV-1
      virions with an integrase-to-INI1/hSNF5 stoichiometry of approximately 2:1 (molar
      ratio). In addition, we show that INI1/hSNF5 is not incorporated into related
      primate lentiviral and murine retroviral particles despite the abundance of the
      protein in producer cells. We have found that the specificity in incorporation of
      INI1/hSNF5 into HIV-1 virions is directly correlated with its ability to
      exclusively interact with HIV-1 integrase but not with other retroviral
      integrases. This specificity is also reflected in our finding that the
      transdominant mutant S6, harboring the minimal integrase interaction domain of
      INI1/hSNF5, blocks HIV-1 particle production but not that of the other
      retroviruses in 293T cells. Taken together, these results suggest that INI1/hNSF5
      is a host factor restricted for HIV-1 and that S6 acts as a highly specific and
      potent inhibitor of HIV-1 replication.

PMID- 14963119
TI  - IkappaB kinase is a critical regulator of chemokine expression and lung
      inflammation in respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) is the major etiologic agent of severe epidemic
      lower respiratory tract infections in infancy. Airway mucosal inflammation plays
      a critical role in the pathogenesis of RSV disease in both natural and
      experimental infections. RSV is among the most potent biological stimuli that
      induce the expression of inflammatory genes, including those encoding chemokines,
      but the mechanism(s) that controls virus-mediated airway inflammation in vivo has
      not been fully elucidated. Herein we show that the inoculation of BALB/c mice
      with RSV results in rapid activation of the multisubunit IkappaB kinase (IKK) in
      lung tissue. IKK transduces upstream activating signals into the rate-limiting
      phosphorylation (and proteolytic degradation) of IkappaBalpha, the inhibitory
      subunit that under normal conditions binds to the nuclear factor (NF)-kappaB
      complex and keeps it in an inactive cytoplasmic form. Mice treated intranasally
      with interleukin-10 or with a specific cell-permeable peptide that blocks the
      association of the catalytic subunit IKKbeta with the regulatory protein NEMO
      showed a striking reduction of lung NF-kappaB DNA binding activity, chemokine
      gene expression, and airway inflammation in response to RSV infection. These
      findings suggest that IKKbeta may be a potential target for the treatment of
      acute or chronic inflammatory diseases of the lung.

PMID- 14963120
TI  - Genetic basis of hypersusceptibility to protease inhibitors and low replicative
      capacity of human immunodeficiency virus type 1 strains in primary infection.
AB  - The initial virus strains from as many as 12% of individuals with primary human
      immunodeficiency virus (HIV) infection have a 50% inhibitory concentration </=0.4
      fold that of HIV type 1(NL4-3) (HIV-1(NL4-3)) to ritonavir (hypersusceptibility
      [HS]). There is also substantial variation in replicative capacity (RC) or an in
      vitro assay of the contributions of protease (PR) and reverse transcriptase to
      viral fitness. In chronically infected antiretrovirally treated patients,
      amprenavir HS has been associated with the mutation N88S in PR, but this mutation
      is not seen in untreated patients. In this study, virus strains from 182 cases of
      primary HIV infection were analyzed, and a highly significant association between
      HS and low RC (</=10% that of HIV-1(NL4-3)) was observed (P < 10(-6)).
      Multivariate analysis was used to determine the genotypic basis of ritonavir HS,
      analyzing all polymorphic amino acid sites and insertions from p7gag through PR.
      Decision tree models developed on the entire Gag-plus-PR data set and on PR alone
      gave overall correct classifications of 73 and 72%, respectively, on cross
      validation. They were also able to predict low RC, with sensitivities of 69 and
      62% and specificities of 84 and 70%, respectively. The analysis shows that
      ritonavir HS in untreated primary HIV infection is not associated with single
      mutations but with combinations of amino acids at polymorphic sites and that the
      same genotypes which confer HS to PR inhibitors confer low RC. This supports the
      view that variation in PR function is directly responsible for variation in
      fitness among strains in primary infection.

PMID- 14963121
TI  - Underwhelming the immune response: effect of slow virus growth on CD8+-T
      lymphocyte responses.
AB  - The speed of virus replication has typically been seen as an advantage for a
      virus in overcoming the ability of the immune system to control its population
      growth. Under some circumstances, the converse may also be true: more slowly
      replicating viruses may evoke weaker cellular immune responses and therefore
      enhance their likelihood of persistence. Using the model of lymphocytic
      choriomeningitis virus (LCMV) infection in mice, we provide evidence that slowly
      replicating strains induce weaker cytotoxic-T-lymphocyte (CTL) responses than a
      more rapidly replicating strain. Conceptually, we show a "bell-shaped"
      relationship between the LCMV growth rate and the peak CTL response. Quantitative
      analysis of human hepatitis C virus infections suggests that a reduction in virus
      growth rate between patients during the incubation period is associated with a
      spectrum of disease outcomes, from fulminant hepatitis at the highest rate of
      viral replication through acute resolving to chronic persistence at the lowest
      rate. A mathematical model for virus-CTL population dynamics (analogous to
      predator [CTL]-prey [virus] interactions) is applied in the clinical data-driven
      analysis of acute hepatitis B virus infection. The speed of viral replication,
      through its stimulus of host CTL responses, represents an important factor
      influencing the pathogenesis and duration of virus persistence within the human
      host. Viruses with lower growth rates may persist in the host because they "sneak
      through" immune surveillance.

PMID- 14963122
TI  - Expansion of protective CD8+ T-cell responses driven by recombinant
      cytomegaloviruses.
AB  - CD8(+) T cells are critical for the control of many persistent viral infections,
      such as human immunodeficiency virus, hepatitis C virus, Epstein-Barr virus, and
      cytomegalovirus (CMV). In most infections, large CD8(+)-T-cell populations are
      induced early but then contract and are maintained thereafter at lower levels. In
      contrast, CD8(+) T cells specific for murine CMV (MCMV) have been shown to
      gradually accumulate after resolution of primary infection. This unique behavior
      is restricted to certain epitopes, including an immunodominant epitope derived
      from the immediate-early 1 (IE1) gene product. To explore the mechanism behind
      this further, we measured CD8(+)-T-cell-mediated immunity induced by recombinant
      MCMV-expressing epitopes derived from influenza A virus or lymphocytic
      choriomeningitis virus placed under the control of an IE promoter. We observed
      that virus-specific CD8(+)-T-cell populations were induced and that these
      expanded gradually over time. Importantly, these CD8(+) T cells provided long
      term protection against challenge without boosting. These results demonstrate a
      unique pattern of accumulating T cells, which provide long-lasting immune
      protection, that is independent of the initial immunodominance of the epitope and
      indicates the potential of T-cell-inducing vaccines based on persistent vectors.

PMID- 14963123
TI  - Promoting trimerization of soluble human immunodeficiency virus type 1 (HIV-1)
      Env through the use of HIV-1/simian immunodeficiency virus chimeras.
AB  - The envelope proteins (Env) of human immunodeficiency virus type 1 (HIV-1) and
      simian immunodeficiency virus (SIV) form homo-oligomers in the endoplasmic
      reticulum. The oligomeric structure of Env is maintained, but is less stable,
      after cleavage in a Golgi compartment and transport to the surface of infected
      cells. Functional, virion-associated HIV-1 and SIV Env have an almost exclusively
      trimeric structure. In addition, a soluble form of SIV Env (gp140) forms a nearly
      homogeneous population of trimers. Here, we describe the oligomeric structure of
      soluble, uncleaved HIV-1 gp140 and modifications that promote a stable trimeric
      structure. Biochemical and biophysical analyses, including sedimentation
      equilibrium and scanning transmission electron microscopy, revealed that
      unmodified HIV-1 gp140 purified as a heterogeneous range of oligomeric species,
      including dimers and aggregates. Deletion of the V2 domain alone or, especially,
      both the V1 and V2 domains reduced dimer formation but promoted aggregation
      rather than trimerization. Expressing gp140 with mannose-only oligosaccharides
      did not eliminate heterogeneity. Replacement of the entire gp41 segment of HIV-1
      gp140 or just the N-terminal half (85 amino acids) of this segment with the
      corresponding region of SIV was sufficient to confer efficient trimerization for
      gp140 derived from clade B and C isolates. Importantly, the relatively small
      segment of the HIV Env replaced by SIV sequences contains no known targets of
      neutralizing antibody. The soluble trimeric form of HIV-1 Env should prove useful
      for assessment of antigenic structure and immunogenicity.

PMID- 14963124
TI  - Role for CCR5Delta32 protein in resistance to R5, R5X4, and X4 human
      immunodeficiency virus type 1 in primary CD4+ cells.
AB  - CCR5Delta32 is a loss-of-function mutation that abolishes cell surface expression
      of the human immunodeficiency virus (HIV) coreceptor CCR5 and provides genetic
      resistance to HIV infection and disease progression. Since CXCR4 and other HIV
      coreceptors also exist, we hypothesized that CCR5Delta32-mediated resistance may
      be due not only to the loss of CCR5 function but also to a gain-of-function
      mechanism, specifically the active inhibition of alternative coreceptors by the
      mutant CCR5Delta32 protein. Here we demonstrate that efficient expression of the
      CCR5Delta32 protein in primary CD4(+) cells by use of a recombinant adenovirus
      (Ad5/Delta32) was able to down-regulate surface expression of both wild-type CCR5
      and CXCR4 and to confer broad resistance to R5, R5X4, and X4 HIV type 1 (HIV-1).
      This may be important clinically, since we found that CD4(+) cells purified from
      peripheral blood mononuclear cells of individuals who were homozygous for
      CCR5Delta32, which expressed the mutant protein endogenously, consistently
      expressed lower levels of CXCR4 and showed less susceptibility to X4 HIV-1
      isolates than cells from individuals lacking the mutation. Moreover, CD4(+) cells
      from individuals who were homozygous for CCR5Delta32 expressed the mutant protein
      in five of five HIV-exposed, uninfected donors tested but not in either of two
      HIV-infected donors tested. The mechanism of inhibition may involve direct
      scavenging, since we were able to observe a direct interaction of CCR5 and CXCR4
      with CCR5Delta32, both by genetic criteria using the yeast two-hybrid system and
      by biochemical criteria using the coimmunoprecipitation of heterodimers. Thus,
      these results suggest that at least two distinct mechanisms may account for
      genetic resistance to HIV conferred by CCR5Delta32: the loss of wild-type CCR5
      surface expression and the generation of CCR5Delta32 protein, which functions as
      a scavenger of both CCR5 and CXCR4.

PMID- 14963125
TI  - The AU-rich RNA recombination hot spot sequence of Brome mosaic virus is
      functional in tombusviruses: implications for the mechanism of RNA recombination.
AB  - RNA recombination can be facilitated by recombination signals present in viral
      RNAs. Among such signals are short sequences with high AU contents that
      constitute recombination hot spots in Brome mosaic virus (BMV) and retroviruses.
      In this paper, we demonstrate that a defective interfering (DI) RNA, a model
      template associated with Tomato bushy stunt virus (TBSV), a tombusvirus,
      undergoes frequent recombination in plants and protoplast cells when it carries
      the AU-rich hot spot sequence from BMV. Similar to the situation with BMV, most
      of the recombination junction sites in the DI RNA recombinants were found within
      the AU-rich region. However, unlike BMV or retroviruses, where recombination
      usually occurred with precision between duplicated AU-rich sequences, the
      majority of TBSV DI RNA recombinants were imprecise. In addition, only one copy
      of the AU-rich sequence was essential to promote recombination in the DI RNA. The
      selection of junction sites was also influenced by a putative cis-acting element
      present in the DI RNA. We found that this RNA sequence bound to the TBSV
      replicase proteins more efficiently than did control nonviral sequences,
      suggesting that it might be involved in replicase "landing" during the template
      switching events. In summary, evidence is presented that a tombusvirus can use
      the recombination signal of BMV. This supports the idea that common AU-rich
      recombination signals might promote interviral recombination between unrelated
      viruses.

PMID- 14963126
TI  - A cysteine-rich plant protein potentiates Potyvirus movement through an
      interaction with the virus genome-linked protein VPg.
AB  - We have identified a cellular factor that interacts with the virus genome-linked
      proteins (VPgs) of a diverse range of potyviruses. The factor, called Potyvirus
      VPg-interacting protein (PVIP), is a plant-specific protein with homologues in
      all the species examined, i.e., pea, Arabidopsis thaliana, and Nicotiana
      benthamiana. The sequence of PVIP does not identify a specific function, although
      the existence of a "PHD finger" domain may implicate the protein in
      transcriptional control through chromatin remodeling. Deletion analysis using the
      yeast two-hybrid system showed that the determinants of the interaction lay close
      to the N terminus of VPg; indeed, the N-terminal 16 amino acids were shown to be
      both necessary and sufficient for the interaction with at least one PVIP protein.
      From a sequence comparison of different potyvirus VPg proteins, a specific amino
      acid at position 12 was directly implicated in the interaction. This part of VPg
      is distinct from regions associated with other functional roles of VPg. Through
      mutation of Turnip mosaic virus (TuMV) at VPg position 12, we showed that the
      interaction with PVIP affected systemic symptoms in infected plants. This
      resulted from reduced cell-to-cell and systemic movement more than reduced virus
      replication, as visualized by comparing green fluorescent protein-tagged wild
      type and mutant viruses. Furthermore, by using RNA interference of PVIP in
      Arabidopsis, we showed that reduced expression of PVIP genes reduced
      susceptibility to TuMV infection. We conclude that PVIP functions as an ancillary
      factor to support potyvirus movement in plants.

PMID- 14963127
TI  - Characterization of rotavirus cell entry.
AB  - While recently we have learned much about the viral and cellular proteins
      involved in the initial attachment of rotaviruses to MA104 cells, the mechanism
      by which these viruses reach the interior of the cell is poorly understood. For
      this study, we observed the effects of drugs and of dominant-negative mutants,
      known to impair clathrin-mediated endocytosis and endocytosis mediated by
      caveolae, on rotavirus cell infection. Rotaviruses were able to enter cells in
      the presence of compounds that inhibit clathrin-mediated endocytosis as well as
      cells overexpressing a dominant-negative form of Eps15, a protein crucial for the
      assembly of clathrin coats. We also found that rotaviruses infected cells in
      which caveolar uptake was blocked; treatment with the cholesterol binding agents
      nystatin and filipin, as well as transfection of cells with dominant-negative
      caveolin-1 and caveolin-3 mutants, had no effect on rotavirus infection.
      Interestingly, cells treated with methyl-beta-cyclodextrin, a drug that
      sequesters cholesterol from membranes, and cells expressing a dominant-negative
      mutant of the large GTPase dynamin, which is known to function in several
      membrane scission events, were not infected by rotaviruses, indicating that
      cholesterol and dynamin play a role in the entry of rotaviruses.

PMID- 14963128
TI  - Role of human immunodeficiency virus type 1 matrix phosphorylation in an early
      postentry step of virus replication.
AB  - The matrix domain (MA) is important for targeting of human immunodeficiency virus
      type 1 Gag assembly to the plasma membrane, envelope incorporation into virions,
      preintegration complex import into the nucleus, and nuclear export of viral RNA.
      Myristylation and phosphorylation are key regulatory events for MA function.
      Previous studies have indicated that MA phosphorylation at serine (Ser) residues
      is important for viral replication. This study defines the molecular mechanisms
      of virus particle assembly and infectivity through a detailed study of the role
      of MA serine phosphorylation. We show that the combined mutation of Ser residues
      at positions 9, 67, 72, and 77 impairs viral infectivity in dividing and
      nondividing cells, although the assembly of these Ser mutant viruses is
      comparable to that of wild-type virus. This defect can be rescued by pseudotyping
      these mutant viruses with vesicular stomatitis virus G protein, suggesting that
      these serine residues are critical in an early postentry step of viral infection.
      The phosphorylation level of MA in defective mutant viruses was severely reduced
      compared to that of the wild type, suggesting that phosphorylation of Ser-9, -67,
      -72, and -77 is important for an early postentry step during virus infection.

PMID- 14963129
TI  - Cell cycle requirements for transduction by foamy virus vectors compared to those
      of oncovirus and lentivirus vectors.
AB  - Retroviral vectors based on foamy viruses (FV) are efficient gene delivery
      vehicles for therapeutic and research applications. While previous studies have
      shown that FV vectors transduce quiescent cell cultures more efficiently than
      oncoviral vectors, their specific cell cycle requirements have not been
      determined. Here we compare the transduction frequencies of FV vectors with those
      of onco- and lentiviral vectors in nondividing and dividing normal human
      fibroblasts by several methods. FV vectors transduced serum-deprived fibroblast
      cultures more efficiently than oncoretroviral vectors and at rates comparable to
      those of lentiviral vectors. However, in these cultures FV vectors only
      transduced a subpopulation of proliferating cells, as determined by
      bromodeoxyuridine staining for DNA synthesis. In contrast to lentiviral vectors,
      FV vectors were unable to transduce human fibroblasts arrested by aphidicolin
      (G(1)/S phase) or gamma-irradiation (G(2) phase), and a partial cell cycle that
      included mitosis but not DNA synthesis was required. We could not determine if
      mitosis facilitated nuclear entry of FV vectors, since cell-free vector
      preparations contained long terminal repeat circles, precluding their use as
      nuclear markers. In contrast to oncoviral vectors, both FV and lentiviral vectors
      efficiently transduced G(0) fibroblasts that were later stimulated to divide. In
      the case of FV vectors, this was due to the persistence of a stable transduction
      intermediate in quiescent cells. Our findings support the use of FV vectors as a
      safe and effective alternative to lentiviral vectors for ex vivo transduction of
      stem cells that are quiescent during culture but divide following
      transplantation.

PMID- 14963130
TI  - Investigation of the susceptibility of human cell lines to bovine herpesvirus 4
      infection: demonstration that human cells can support a nonpermissive persistent
      infection which protects them against tumor necrosis factor alpha-induced
      apoptosis.
AB  - Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus that has a worldwide
      distribution in the population of cattle. Many factors make human contamination
      by BoHV-4 likely to occur. In this study, we performed in vitro experiments to
      assess the risk and the consequences of human infection by BoHV-4. First, by
      using a recombinant BoHV-4 strain expressing enhanced green fluorescent protein
      under the control of the human cytomegalovirus immediate-early gene promoter, we
      tested 21 human cell lines for their sensitivity and their permissiveness to BoHV
      4 infection. These experiments revealed that human cell lines from lymphoid and
      myeloid origins were resistant to infection, whereas epithelial cells, carcinoma
      cells, or adenocarcinoma cells isolated from various organs were sensitive but
      poorly permissive to BoHV-4 infection. Second, by using the HeLa cell line as a
      model of human cells sensitive but not permissive to BoHV-4 infection, we
      investigated the resistance of infected cells to apoptosis and the persistence of
      the infection through cellular divisions. The results obtained can be summarized
      as follows. (i) BoHV-4 nonpermissive infection of HeLa cells protects them
      against tumor necrosis factor alpha-induced apoptosis. (ii) BoHV-4 infection of
      HeLa cells persists in cell culture; however, the percentage of infected cells
      decreases with time due to erratic transmission of the viral genome through cell
      division. (iii) BoHV-4 infection has no effect on the rate of HeLa cell division.
      Altogether, these data suggest that BoHV-4 could infect humans. This study also
      stresses the importance of considering the insidious effects of nonpermissive
      infection when the biosafety of animal gammaherpesviruses for humans is being
      considered.

PMID- 14963131
TI  - Vaccinia virus A28L gene encodes an essential protein component of the virion
      membrane with intramolecular disulfide bonds formed by the viral cytoplasmic
      redox pathway.
AB  - We report the initial characterization of the product of the vaccinia virus A28L
      gene, which is highly conserved in all sequenced poxviruses. Our studies showed
      that the A28 protein is expressed at late times during the virus replication
      cycle and is a membrane component of the intracellular mature virion. An N
      terminal hydrophobic sequence, present in all poxvirus A28 orthologs, anchors the
      protein in the virion surface membrane so that most of it is exposed to the
      cytoplasm. The cytoplasmic domain contains four conserved cysteines, which form
      two intramolecular disulfide bonds. Disulfide bond formation depended on the
      expression of three viral proteins, E10, A2.5, and G4, which together comprise a
      conserved cytoplasmic redox pathway. A28 is the third identified substrate of
      this pathway; the others are the L1 and F9 proteins. We constructed a conditional
      lethal recombinant vaccinia virus with an inducible A28L gene. The recombinant
      virus was propagated in the presence of inducer but was unable to replicate and
      spread in its absence. During a single round of an abortive infection in the
      absence of inducer, the synthesis and processing of viral proteins, assembly of
      intra- and extracellular virions, and formation of actin tails occurred normally.
      In another paper (T. Senkevich, B. M. Ward, and B. Moss, J. Virol. 78:2357-2366,
      2004), we have demonstrated that virions assembled without A28 cannot carry out a
      second round of infection because they are defective in cell penetration.

PMID- 14963132
TI  - Vaccinia virus entry into cells is dependent on a virion surface protein encoded
      by the A28L gene.
AB  - The A28L gene of vaccinia virus is conserved in all poxviruses and encodes a
      protein that is anchored to the surface of infectious intracellular mature
      virions (IMV) and consequently lies beneath the additional envelope of
      extracellular virions. A conditional lethal recombinant vaccinia virus, vA28-HAi,
      with an inducible A28L gene, undergoes a single round of replication in the
      absence of inducer, producing IMV, as well as extracellular virions with actin
      tails, but fails to infect neighboring cells. We show here that purified A28
      deficient IMV appeared to be indistinguishable from wild-type IMV and were
      competent to synthesize RNA in vitro. Nevertheless, A28-deficient virions did not
      induce cytopathic effects, express early genes, or initiate a productive
      infection. Although A28-deficient IMV bound to the surface of cells, their cores
      did not penetrate into the cytoplasm. An associated defect in membrane fusion was
      demonstrated by the failure of low pH to trigger syncytium formation when cells
      were infected with vA28-HAi in the absence of inducer (fusion from within) or
      when cells were incubated with a high multiplicity of A28-deficient virions
      (fusion from without). The correlation between the entry block and the inability
      of A28-deficient virions to mediate fusion provided compelling evidence for a
      relationship between these events. Because repression of A28 inhibited cell-to
      cell spread, which is mediated by extracellular virions, all forms of vaccinia
      virus regardless of their outer coat must use a common A28-dependent mechanism of
      cell penetration. Furthermore, since A28 is conserved, all poxviruses are likely
      to penetrate cells in a similar way.

PMID- 14963133
TI  - Alterations of pr-M cleavage and virus export in pr-M junction chimeric dengue
      viruses.
AB  - During the export of flavivirus particles through the secretory pathway, a viral
      envelope glycoprotein, prM, is cleaved by the proprotein convertase furin; this
      cleavage is required for the subsequent rearrangement of receptor-binding E
      glycoprotein and for virus infectivity. Similar to many furin substrates, prM in
      vector-borne flaviviruses contains basic residues at positions P1, P2, and P4
      proximal to the cleavage site; in addition, a number of charged residues are
      found at position P3 and between positions P5 and P13 that are conserved for each
      flavivirus antigenic complex. The influence of additional charged residues on pr
      M cleavage and virus replication was investigated by replacing the 13-amino-acid,
      cleavage-proximal region of a dengue virus (strain 16681) with those of tick
      borne encephalitis virus (TBEV), yellow fever virus (YFV), and Japanese
      encephalitis virus (JEV) and by comparing the resultant chimeric viruses
      generated from RNA-transfected mosquito cells. Among the three chimeric viruses,
      cleavage of prM was enhanced to a larger extent in JEVpr/16681 than in
      YFVpr/16681 but was slightly reduced in TBEVpr/16681. Unexpectedly, JEVpr/16681
      exhibited decreased focus size, reduced peak titer, and depressed replication in
      C6/36, PS, and Vero cell lines. The reduction of JEVpr/16681 multiplication
      correlated with delayed export of infectious virions out of infected cells but
      not with changes in specific infectivity. Binding of JEVpr/16681 to immobilized
      heparin and the heparin-inhibitable infection of cells were not altered. Thus,
      diverse pr-M junction-proximal sequences of flaviviruses differentially influence
      pr-M cleavage when tested in a dengue virus prM background. More importantly,
      greatly enhanced prM cleavability adversely affects dengue virus export while
      exerting a minimal effect on infectivity. Because extensive changes of charged
      residues at the pr-M junction, as in JEVpr/16681, were not observed among a large
      number of dengue virus isolates, these results provide a possible mechanism by
      which the sequence conservation of the pr-M junction of dengue virus is
      maintained in nature.

PMID- 14963134
TI  - The matrix protein of Marburg virus is transported to the plasma membrane along
      cellular membranes: exploiting the retrograde late endosomal pathway.
AB  - VP40, the matrix protein of Marburg virus, is a peripheral membrane protein that
      has been shown to associate with membranes of multivesicular bodies (MVBs) (L.
      Kolesnikova, H. Bugany, H.-D. Klenk, and S. Becker, J. Virol. 76:1825-1838,
      2002). The present study revealed that VP40 is bound to cellular membranes
      rapidly after synthesis. Time course studies were performed to trace the
      distribution of VP40 during the course of expression. First, VP40 was
      homogenously distributed throughout the cytoplasm, although the majority of
      protein (70%) was already membrane associated. Next, VP40 accumulated in MVBs and
      in tubular protrusions emerging from MVBs. Finally, VP40 appeared in a patch-like
      pattern beneath the plasma membrane. These morphological results were supported
      by iodixanol density gradient analyses. The majority of VP40-positive membranes
      were first detected comigrating with small vesicles. VP40 was then shifted to
      fractions containing endosomal marker proteins, and later, to fractions
      containing plasma membrane marker proteins. Blocking of protein synthesis by use
      of cycloheximide at the time when VP40 was mainly associated with the small
      vesicles did not prevent the redistribution of VP40 to the late endosomes and
      further to the plasma membrane. The inhibition of intracellular vesicular
      trafficking by monensin significantly reduced the appearance of VP40 at the
      plasma membrane. In conclusion, we suggest that the transport of the Marburg
      virus matrix protein VP40 involves its accumulation in MVBs followed by the
      redistribution of VP40-enriched membrane clusters to the plasma membrane.

PMID- 14963135
TI  - The v3 loop is accessible on the surface of most human immunodeficiency virus
      type 1 primary isolates and serves as a neutralization epitope.
AB  - Antibodies (Abs) against the V3 loop of the human immunodeficiency virus type 1
      gp120 envelope glycoprotein were initially considered to mediate only type
      specific neutralization of T-cell-line-adapted viruses. However, recent data show
      that cross-neutralizing V3 Abs also exist, and primary isolates can be
      efficiently neutralized with anti-V3 monoclonal Abs (MAbs). The neutralizing
      activities of anti-V3 polyclonal Abs and MAbs may, however, be limited due to
      antigenic variations of the V3 region, a lack of V3 exposure on the surface of
      intact virions, or Ab specificity. For clarification of this issue, a panel of 32
      human anti-V3 MAbs were screened for neutralization of an SF162-pseudotyped virus
      in a luciferase assay. MAbs selected with a V3 fusion protein whose V3 region
      mimics the conformation of the native virus were significantly more potent than
      MAbs selected with V3 peptides. Seven MAbs were further tested for neutralizing
      activity against 13 clade B viruses in a single-round peripheral blood
      mononuclear cell assay. While there was a spectrum of virus sensitivities to the
      anti-V3 MAbs observed, 12 of the 13 viruses were neutralized by one or more of
      the anti-V3 MAbs. MAb binding to intact virions correlated significantly with
      binding to solubilized gp120s and with the potency of neutralization. These
      results demonstrate that the V3 loop is accessible on the native virus envelope,
      that the strength of binding of anti-V3 Abs correlates with the potency of
      neutralization, that V3 epitopes may be shared rather than type specific, and
      that Abs against the V3 loop, particularly those targeting conformational
      epitopes, can mediate the neutralization of primary isolates.

PMID- 14963136
TI  - The DNA-A component of a plant geminivirus (Indian mung bean yellow mosaic virus)
      replicates in budding yeast cells.
AB  - Understanding the biochemistry of DNA replication of the plant DNA viruses is
      important for the development of antiviral strategies. Since DNA replication is
      little studied in plants, a genetically tractable, easily culturable, eukaryotic
      model system is required to pursue such studies in a facile manner. Here we
      report the development of a yeast model system that supports DNA replication of a
      chosen geminivirus strain, Indian mung bean yellow mosaic virus. The replication
      of plasmid DNA in the model system relies specifically on the virus-derived
      elements and factors. Usage of this model system revealed the role of at least
      one hitherto unknown viral factor for viral DNA replication. The episomal
      characteristic of single-strandedness of replicated plasmid DNA was shown, and
      the expression of viral genes was also confirmed. This model system is expected
      to shed light on the machinery and mechanism involved in geminiviral DNA
      replication in plants.

PMID- 14963137
TI  - Uncleaved NS2-3 is required for production of infectious bovine viral diarrhea
      virus.
AB  - Despite increasing characterization of pestivirus-encoded proteins, functions for
      nonstructural (NS) proteins NS2, NS2-3, NS4B, and NS5A have not yet been
      reported. Here we investigated the function of bovine viral diarrhea virus (BVDV)
      uncleaved NS2-3. To test whether NS2-3 has a discrete function, the uncleaved
      protein was specifically abolished in two ways: first by inserting a ubiquitin
      monomer between NS2 and NS3, and second by placing an internal ribosome entry
      site between the two proteins (a bicistronic genome). In both cases, complete
      processing of NS2-3 prevented infectious virion formation without affecting RNA
      replication. We tested the hypothesis that uncleaved NS2-3 was involved in
      morphogenesis by creating a bicistronic genome in which NS2-3 was restored in the
      second cistron. With this genome, both uncleaved NS2-3 expression and particle
      production returned. We then investigated the minimal regions of the polyprotein
      that could rescue an NS2-3 defect by developing a trans-complementation assay. We
      determined that the expression of NS4A in cis with NS2-3 markedly increased its
      activity, while p7 could be supplied in trans. Based on these data, we propose a
      model for NS2-3 action in virion morphogenesis.

PMID- 14963138
TI  - Unselected mutations in the human immunodeficiency virus type 1 genome are mostly
      nonsynonymous and often deleterious.
AB  - Mutation rates of human immunodeficiency virus type 1 (HIV-1) genomes have been
      estimated using purified reverse transcriptase or single-round infection system.
      Since small sequences were used as templates, the overall mutation rates could
      only be extrapolated and the biological significance of mutations is unknown. For
      direct estimation of HIV-1 mutation rates and understanding of the potential
      biological influences of mutations, we obtained 19 complete or nearly full-length
      proviral genomes from single-round-infected adherent cells of lymphocytes by
      using a lambda phage library method and a long-range PCR technique. Analysis of
      160,000 bp of sequences showed that the overall mutation rate of HIV-1 genomes
      was 5.4 x 10(-5) per base per replication cycle. On average, 1.1 mutations
      (range, 0 to 3) were generated in each viral genome during one infection cycle.
      Inspection of the mutations in the HIV-1 genome revealed that all site mutations
      within protein-coding regions were nonsynonymous mutations. Among all mutations,
      half were deleterious (premature stop codon and deletions) and would result in
      defective genomes. By applying the same system to an HIV-1 genome with a G262A
      mutation in the thumb region of the reverse transcriptase, a significant increase
      was observed in deletion and insertion mutation rates but no increase in the
      overall mutation rate in viral genomes was found.

PMID- 14963139
TI  - Highly uneven distribution of tenofovir-selected simian immunodeficiency virus in
      different anatomical sites of rhesus macaques.
AB  - Antiviral tenofovir monotherapy was used to determine whether drug-selected
      simian immunodeficiency virus (SIV) variants replaced their wild-type progenitors
      at the same rate in different tissues of six rhesus macaques. The relative
      frequencies of drug-resistant and wild-type genotypes were measured
      longitudinally in blood and in 23 lymphoid and nonlymphoid tissues collected at
      necropsy. The mutant/wild-type genotype ratio was measured using a heteroduplex
      tracking assay targeting tenofovir-selected SIV reverse transcriptase codons.
      After the initiation of tenofovir treatment in animals with high steady-state
      viremia levels, resistant genotypes emerged in the plasma within 1 to 8 weeks and
      in five of six cases reached frequencies of nearly 100% within 4 to 25 weeks. The
      appearance of tenofovir-resistant genotypes in peripheral blood mononuclear cell
      (PBMC) DNA was generally delayed by 1 to 2 weeks and in one case was completely
      absent. Necropsies performed 8 to 55 weeks after the initiation of tenofovir
      treatment showed the frequency of resistant SIV genotypes to be generally higher
      in tissue RNA than DNA fractions. The frequency of drug-resistant genotypes
      varied widely between anatomical sites, including different lymph nodes of the
      same animal. Except for the epidydimis, the tissues with the lowest rates of
      proviral replacement by tenofovir-resistant genotypes differed between animals.
      The highly uneven distribution of tenofovir-resistant genotypes in different
      tissues seen shortly after the initiation of tenofovir monotherapy may reflect
      differences in local antiviral drug selection pressures and/or the stochastic
      effect of small effective populations of drug-resistant variants randomly seeding
      different anatomical sites early in therapy.

PMID- 14963140
TI  - Human CD4+ CD25+ regulatory T cells control T-cell responses to human
      immunodeficiency virus and cytomegalovirus antigens.
AB  - Regulatory T (T(R)) cells maintain tolerance to self-antigens and control immune
      responses to alloantigens after organ transplantation. Here, we show that CD4(+)
      CD25(+) human T(R) cells suppress virus-specific T-cell responses. Depletion of
      T(R) cells from peripheral blood mononuclear cells enhances T-cell responses to
      cytomegalovirus and human immunodeficiency virus antigens. We propose that
      chronic viral infections lead to induction of suppressive T(R) cells that inhibit
      the antiviral immune response.

PMID- 14963141
TI  - African swine fever virus multigene family 360 genes affect virus replication and
      generalization of infection in Ornithodoros porcinus ticks.
AB  - Recently, we reported that African swine fever virus (ASFV) multigene family
      (MGF) 360 and 530 genes are significant swine macrophage host range determinants
      that function by promoting infected-cell survival. To examine the function of
      these genes in ASFV's arthropod host, Ornithodoros porcinus porcinus, an
      MGF360/530 gene deletion mutant (Pr4Delta35) was constructed from an ASFV isolate
      of tick origin, Pr4. Pr4Delta35 exhibited a significant growth defect in ticks.
      The deletion of six MGF360 and two MGF530 genes from Pr4 markedly reduced viral
      replication in infected ticks 100- to 1,000-fold. To define the minimal set of
      MGF360/530 genes required for tick host range, additional gene deletion mutants
      lacking individual or multiple MGF genes were constructed. The deletion mutant
      Pr4Delta3-C2, which lacked three MGF360 genes (3HL, 3Il, and 3LL), exhibited
      reduced viral growth in ticks. Pr4Delta3-C2 virus titers in ticks were
      significantly reduced 100- to 1,000-fold compared to control values at various
      times postinfection. In contrast to the parental virus, with which high levels of
      virus replication were observed in the tissues of infected adults, Pr4Delta3-C2
      replication was not detected in the midgut, hemolymph, salivary gland, coxal
      gland, or reproductive organs at 15 weeks postinfection. These data indicate that
      ASFV MGF360 genes are significant tick host range determinants and that they are
      required for efficient virus replication and generalization of infection. The
      impaired virus replication of Pr4Delta3-C2 in the tick midgut likely accounts for
      the absence of the generalized infection that is necessary for the natural
      transmission of virus from ticks to pigs.

PMID- 14963144
TI  - Galpha protein selectivity determinant specified by a viral chemokine receptor
      conserved region in the C tail of the human herpesvirus 8 g protein-coupled
      receptor.
AB  - The viral G-protein coupled receptor (vGPCR) specified by human herpesvirus 8
      (HHV-8) open reading frame 74 (ORF74) is a ligand-independent chemokine receptor
      that has structural and functional homologues among other characterized
      gammaherpesviruses and related receptors in the betaherpesviruses. Sequence
      comparisons of the gammaherpesvirus vGPCRs revealed a highly conserved region in
      the C tail, just distal to the seventh transmembrane domain. Mutagenesis of the
      corresponding codons of HHV-8 ORF74 was carried out to provide C-tail-altered
      proteins for functional analyses. By measuring receptor-activated vascular
      endothelial growth factor promoter induction and NF-kappaB, mitogen-activated
      protein kinase, and Ca(2+) signaling, we found that while some altered receptors
      showed general signaling deficiencies, others had distinguishable activation
      profiles, suggestive of selective Galpha protein coupling. This was supported by
      the finding that vGPCR and representative functionally altered variants, vGPCR.8
      (R322W) and vGPCR.15 (M325S), were affected differently by inhibitors of
      Galpha(i) (pertussis toxin), protein kinase C (GF109203X), and
      phosphatidylinositol 3-kinase (wortmannin). Consistent with the signaling data,
      [(35)S]GTPgammaS incorporation assays revealed preferential coupling of vGPCR.15
      to Galpha(q) and an inability of vGPCR.8 to couple functionally to Galpha(q).
      However, both variants, wild-type vGPCR, and a C-tail deletion version of the
      receptor were equally able to associate physically with Galpha(q). Combined, our
      data demonstrate that HHV-8 vGPCR contains discrete sites of Galpha interaction
      and that receptor residues in the proximal region of the cytoplasmic tail are
      determinants of Galpha protein coupling specificity.

PMID- 14963145
TI  - Foamy virus integration.
AB  - It had been suggested that during integration of spumaretroviruses (foamy
      viruses) the right (U5) end of the cDNA is processed, while the left (U3) remains
      uncleaved. We confirmed this hypothesis by sequencing two-long terminal repeat
      (LTR) circle junctions of unintegrated DNA. Based on an infectious foamy virus
      molecular clone, a set of constructs harboring mutations at the 5' end of the U3
      region in the 3' LTR was analyzed for particle export, reverse transcription, and
      replication. Following transient transfection some mutants were severely impaired
      in generating infectious virus, while others replicated almost like the wild
      type. The replication competence of the mutants was unrelated to the cleavability
      of the newly created U3 end. This became obvious with two mutants both belonging
      to the high-titer type. One mutant containing a dinucleotide artificially
      transferred from the right to the left end was trimmed upon integration, while
      another one with an unrelated dinucleotide in that place was not. The latter
      construct in particular showed that the canonical TG motif at the beginning of
      the provirus is not essential for foamy virus integration.

PMID- 14963146
TI  - Influence of long terminal repeat and env on the virulence phenotype of equine
      infectious anemia virus.
AB  - The molecular clones pSPeiav19 and p19/wenv17 of equine infectious anemia virus
      (EIAV) differ in env and long terminal repeats (LTRs) and produce viruses
      (EIAV(19) and EIAV(17), respectively) of dramatically different virulence
      phenotypes. These constructs were used to generate a series of chimeric clones to
      test the individual contributions of LTR, surface (SU), and transmembrane
      (TM)/Rev regions to the disease potential of the highly virulent EIAV(17). The
      LTRs of EIAV(19) and EIAV(17) differ by 16 nucleotides in the transcriptional
      enhancer region. The two viruses differ by 30 amino acids in SU, by 17 amino
      acids in TM, and by 8 amino acids in Rev. Results from in vivo infections with
      chimeric clones indicate that both LTR and env of EIAV(17) are required for the
      development of severe acute disease. In the context of the EIAV(17) LTR, SU
      appears to have a greater impact on virulence than does TM. EIAV(17SU),
      containing only the TM/Rev region from the avirulent parent, induced acute
      disease in two animals, while a similar infectious dose of EIAV(17TM) (which
      derives SU from the avirulent parent) did not. Neither EIAV(17SU) nor EIAV(17TM)
      produced lethal disease when administered at infectious doses that were 6- to 30
      fold higher than a lethal dose of the parental EIAV(17). All chimeric clones
      replicated in primary equine monocyte-derived macrophages, and there was no
      apparent correlation between macrophage tropism and virulence phenotype.

PMID- 14963148
TI  - Vaccinia virus A36R membrane protein provides a direct link between intracellular
      enveloped virions and the microtubule motor kinesin.
AB  - Previous work demonstrated that intracellular enveloped vaccinia virus virions
      use microtubules to move from the site of membrane wrapping to the cell
      periphery. The mechanism and direction of intracellular virion movement predicted
      that viral proteins directly or indirectly interact with the microtubule motor
      protein kinesin. The yeast two-hybrid assay was used to test for interactions
      between the light chain of kinesin and the cytoplasmic tails from five viral
      envelope proteins. We found that the N-terminal tetratricopeptide repeat region
      of the kinesin light chain (KLC-TPR) interacted with the cytoplasmic tail of the
      viral A36R protein. A series of C- and N-terminal truncations of A36R further
      defined a region from residues 81 to 111 that was sufficient for interaction with
      KLC-TPR. Interactions were confirmed by using pull-down assays with purified
      glutathione S-transferase (GST)-A36R and (35)S-labeled KLC-TPR. The defined
      region on A36R for interaction with kinesin overlaps the recently defined region
      (residues 91 to 111) for interaction with the A33R envelope protein. The yeast
      three-hybrid system was used to demonstrate that expression of A33R interrupted
      the interaction between A36R and KLC-TPR, indicating that the binding of A36R is
      mutually exclusive to either A33R or kinesin. Pull-down assays with purified GST
      A36R and (35)S-labeled KLC-TPR in the presence of competing A33R corroborated
      these findings. Collectively, these results demonstrated that the viral A36R
      protein interacts directly with the microtubule motor protein kinesin and that
      the viral protein A33R may regulate this interaction.

PMID- 14963150
TI  - Identification of exogenous forms of human-tropic porcine endogenous retrovirus
      in miniature Swine.
AB  - The replication of porcine endogenous retrovirus subgroup A (PERV-A) and PERV-B
      in certain human cell lines indicates that PERV may pose an infectious risk in
      clinical xenotransplantation. We have previously reported that human-tropic PERVs
      isolated from infected human cells following cocultivation with miniature swine
      peripheral blood mononuclear cells (PBMC) are recombinants of PERV-A with PERV-C.
      Here, we report that these recombinants are exogenous viruses in miniature swine;
      i.e., they are not present in the germ line DNA. These viruses were invariably
      present in miniature swine that transmitted PERV to human cells and were also
      identified in some miniature swine that lacked this ability. These data, together
      with the demonstration of the absence of both replication-competent PERV-A and
      recombinant PERV-A/C loci in the genome of miniature swine (L. Scobie, S. Taylor,
      J. C. Wood, K. M. Suling, G. Quinn, C. Patience, H.-J. Schuurman, and D. E.
      Onions, J. Virol. 78:2502-2509, 2004), indicate that exogenous PERV is the
      principal source of human-tropic virus in these animals. Interestingly, strong
      expression of PERV-C in PBMC correlated with an ability of the PBMC to transmit
      PERV-A/C recombinants in vitro, indicating that PERV-C may be an important factor
      affecting the production of human-tropic PERV. In light of these observations,
      the safety of clinical xenotransplantation from miniature swine will be most
      enhanced by the utilization of source animals that do not transmit PERV to either
      human or porcine cells. Such animals were identified within the miniature swine
      herd and may further enhance the safety of clinical xenotransplantation.

PMID- 14963152
TI  - Absence of replication-competent human-tropic porcine endogenous retroviruses in
      the germ line DNA of inbred miniature Swine.
AB  - The potential transmission of porcine endogenous retroviruses (PERVs) has raised
      concern in the development of porcine xenotransplantation products. Our previous
      studies have resulted in the identification of animals within a research herd of
      inbred miniature swine that lack the capacity to transmit PERV to human cells in
      vitro. In contrast, other animals were capable of PERV transmission. The PERVs
      that were transmitted to human cells are recombinants between PERV-A and PERV-C
      in the post-VRA region of the envelope (B. A. Oldmixon, J. C. Wood, T. A.
      Ericsson, C. A. Wilson, M. E. White-Scharf, G. Andersson, J. L. Greenstein, H. J.
      Schuurman, and C. Patience, J. Virol. 76:3045-3048, 2002); these viruses we term
      PERV-A/C. This observation prompted us to determine whether these human-tropic
      replication-competent (HTRC) PERV-A/C recombinants were present in the genomic
      DNA of these miniature swine. Genomic DNA libraries were generated from one
      miniature swine that transmitted HTRC PERV as well as from one miniature swine
      that did not transmit HTRC PERV. HTRC PERV-A/C proviruses were not identified in
      the germ line DNAs of these pigs by using genomic mapping. Similarly, although
      PERV-A loci were identified in both libraries that possessed long env open
      reading frames, the Env proteins encoded by these loci were nonfunctional
      according to pseudotype assays. In the absence of a germ line source for HTRC
      PERV, further studies are warranted to assess the mechanisms by which HTRC PERV
      can be generated. Once identified, it may prove possible to generate animals with
      further reduced potential to produce HTRC PERV.

PMID- 14963153
TI  - A virulence factor of myxoma virus colocalizes with NF-kappaB in the nucleus and
      interferes with inflammation.
AB  - NF-kappaB is one of the most important elements that coordinate stress-induced,
      immune, and inflammatory responses. Myxoma virus, a member of the Poxviridae
      family responsible for rabbit myxomatosis, codes for several factors that help
      its survival in the host. In this study, we focused on the product of the M150R
      gene. We show that the protein has nine ankyrin repeats (ANKs), with the eighth
      having a close similarity with the nuclear localization signal-containing ANK of
      I-kappaBalpha, which regulates NF-kappaB activity by sequestering it in the
      cytosol. Because the viral protein is targeted to the nucleus, it was named MNF,
      for myxoma nuclear factor. This localization was lost when the eighth ANK was
      removed. In tumor necrosis factor alpha-treated cells, MNF and NF-kappaB
      colocalized as dotted spots in the nucleus. In vivo experiments with a knockout
      virus showed that MNF is a critical virulence factor, with its deletion
      generating an almost apathogenic virus. Detailed histological examinations
      revealed an increase in the inflammatory process in the absence of MNF,
      consistent with the interference of MNF with the NF-kappaB-induced
      proinflammatory pathway. Because MNF has homologs in other poxviruses, such as
      vaccinia, cowpox, and variola viruses, this protein is probably part of a key
      mechanism that contributes to the immunogenic and pathogenic properties of these
      viruses.

PMID- 14963154
TI  - Inhibition of human immunodeficiency virus type 1 replication by RNA interference
      directed against human transcription elongation factor P-TEFb (CDK9/CyclinT1).
AB  - The human positive transcription elongation factor P-TEFb is composed of two
      subunits, cyclin T1 (hCycT1) and CDK9, and is involved in transcriptional
      regulation of cellular genes as well as human immunodeficiency virus type 1 (HIV
      1) mRNA. Replication of HIV-1 requires the Tat protein, which activates
      elongation of RNA polymerase II at the HIV-1 promoter by interacting with hCycT1.
      To understand the cellular functions of P-TEFb and to test whether suppression of
      host proteins such as P-TEFb can modulate HIV infectivity without causing
      cellular toxicity or lethality, we used RNA interference (RNAi) to specifically
      knock down P-TEFb expression by degrading hCycT1 or CDK9 mRNA. RNAi-mediated gene
      silencing of P-TEFb in HeLa cells was not lethal and inhibited Tat
      transactivation and HIV-1 replication in host cells. We also found that CDK9
      protein stability depended on hCycT1 protein levels, suggesting that the
      formation of P-TEFb CDK-cyclin complexes is required for CDK9 stability.
      Strikingly, P-TEFb knockdown cells showed normal P-TEFb kinase activity. Our
      studies suggest the existence of a dynamic equilibrium between active and
      inactive pools of P-TEFb in the cell and indicate that this equilibrium shifts
      towards the active kinase form to sustain cell viability when P-TEFb protein
      levels are reduced. The finding that a P-TEFb knockdown was not lethal and still
      showed normal P-TEFb kinase activity suggested that there is a critical threshold
      concentration of activated P-TEFb required for cell viability and HIV
      replication. These results provide new insights into the regulation of P-TEFb
      function and suggest the possibility that similar mechanisms for monitoring
      protein levels to modulate the activity of proteins may exist for the regulation
      of a variety of other enzymatic pathways.

PMID- 14963155
TI  - In vivo role of nectin-1 in entry of herpes simplex virus type 1 (HSV-1) and HSV
      2 through the vaginal mucosa.
AB  - Herpes simplex virus type 2 (HSV-2) is transmitted through the genital mucosa
      during sexual encounters. In recent years, HSV-1 has also become commonly
      associated with primary genital herpes. The mechanism of viral entry of HSV-1 and
      HSV-2 in the female genital tract is unknown. In order to understand the
      molecular interactions required for HSV entry into the vaginal epithelium, we
      examined the expression of herpesvirus entry mediator nectin-1 in the vagina of
      human and mouse at different stages of their hormonal cycle. Nectin-1 was highly
      expressed in the epithelium of human vagina throughout the menstrual cycle,
      whereas the mouse vaginal epithelium expressed nectin-1 only during the stages of
      the estrous cycle in which mice are susceptible to vaginal HSV infection.
      Furthermore, the ability of nectin-1 to mediate viral entry following
      intravaginal inoculation was examined in a mouse model of genital herpes. Vaginal
      infection with either HSV-1 or HSV-2 was blocked by preincubation of the virus
      with soluble recombinant nectin-1. Viral entry through the vaginal mucosa was
      also inhibited by preincubation of HSV-2 with antibody against gD. Together,
      these results suggest the importance of nectin-1 in mediating viral entry for
      both HSV-1 and HSV-2 in the genital mucosa in female hosts.

PMID- 14963156
TI  - Molecular phylogenetic analyses indicate a wide and ancient radiation of African
      hepatitis delta virus, suggesting a deltavirus genus of at least seven major
      clades.
AB  - Hepatitis D virus (HDV) is a satellite of hepatitis B virus (HBV) for
      transmission and propagation and infects nearly 20 million people worldwide. The
      HDV genome is a compact circular single-stranded RNA genome with extensive
      intramolecular complementarity. Despite its different epidemiological and
      pathological patterns, the variability and geographical distribution of HDV are
      limited to three genotypes and two subtypes that have been characterized to date.
      Phylogenetic reconstructions based on the delta antigen gene and full-length
      genome sequence data show an extensive and probably ancient radiation of African
      lineages, suggesting that the genetic variability of HDV is much more complex
      than was previously thought, with evidence of additional clades. These results
      relate the geographic distribution of HDV more closely to the genetic variability
      of its helper HBV.

PMID- 14963157
TI  - Assembly properties of the human immunodeficiency virus type 1 CA protein.
AB  - During retroviral maturation, the CA protein oligomerizes to form a closed capsid
      that surrounds the viral genome. We have previously identified a series of
      deleterious surface mutations within human immunodeficiency virus type 1 (HIV-1)
      CA that alter infectivity, replication, and assembly in vivo. For this study, 27
      recombinant CA proteins harboring 34 different mutations were tested for the
      ability to assemble into helical cylinders in vitro. These cylinders are composed
      of CA hexamers and are structural models for the mature viral capsid. Mutations
      that diminished CA assembly clustered within helices 1 and 2 in the N-terminal
      domain of CA and within the crystallographically defined dimer interface in the
      CA C-terminal domain. These mutations demonstrate the importance of these regions
      for CA cylinder production and, by analogy, mature capsid assembly. One CA mutant
      (R18A) assembled into cylinders, cones, and spheres. We suggest that these capsid
      shapes occur because the R18A mutation alters the frequency at which pentamers
      are incorporated into the hexagonal lattice. The fact that a single CA protein
      can simultaneously form all three known retroviral capsid morphologies supports
      the idea that these structures are organized on similar lattices and differ only
      in the distribution of 12 pentamers that allow them to close. In further support
      of this model, we demonstrate that the considerable morphological variation seen
      for conical HIV-1 capsids can be recapitulated in idealized capsid models by
      altering the distribution of pentamers.

PMID- 14963158
TI  - Analysis of the 3' cis-acting elements of rubella virus by using replicons
      expressing a puromycin resistance gene.
AB  - A rubella virus (RUB) replicon, RUBrep/PAC, was constructed and used to map the
      3' cis-acting elements (3' CSE) of the RUB genome required for RUB replication.
      The RUBrep/PAC replicon had the structural protein open reading frame partially
      replaced by a puromycin acetyltransferase (PAC) gene. Cells transfected with
      RUBrep/PAC transcripts expressed the PAC gene from the subgenomic RNA, were
      rendered resistant to puromycin, and thus survived selection with this drug. The
      relative survival following puromycin selection of cells transfected with
      transcripts from RUBrep/PAC constructs with mutations in the 3' CSE varied. The
      3' region necessary for optimal relative survival consisted of the 3' 305
      nucleotides (nt), a region conserved in RUB defective-interfering RNAs, and thus
      this region constitutes the 3' CSE. Within the 3' CSE, deletions in the
      approximately 245 nt that overlap the 3' end of the E1 gene resulted in reduced
      relative survivals, ranging from 20 to <1% of the parental replicon survival
      level while most mutations within the approximately 60-nt 3' untranslated region
      (UTR) were lethal. None of the 3' CSE mutations affected in vitro translation of
      the nonstructural protein open reading frame (which is 5' proximal in the genome
      and encodes the enzymes involved in virus RNA replication). In cells transfected
      with replicons with 3' CSE mutations that survived antibiotic selection (i.e.,
      those with mutations in the region of the 3' CSE that overlaps the E1 coding
      region), the amount of replicon-specific minus-strand RNA was uniform; however,
      the accumulation of both plus-strand RNA species, genomic and subgenomic, varied
      widely, indicating that this region of the RUB 3' CSE affects plus-strand RNA
      accumulation rather than minus-strand RNA synthesis.

PMID- 14963159
TI  - Immunization strategies to block the herpes simplex virus type 1 immunoglobulin G
      Fc receptor.
AB  - Herpes simplex virus type 1 (HSV-1) glycoprotein gE functions as an
      immunoglobulin G (IgG) Fc receptor (FcgammaR) that promotes immune evasion. When
      an IgG antibody binds by the F(ab')(2) domain to an HSV antigen, the Fc domain of
      some of the same antibody molecules binds to the FcgammaR, which blocks Fc
      mediated functions. gE is a type 1 membrane glycoprotein with a large ectodomain
      that is expressed on the virion envelope and infected-cell surface. Our goal was
      to determine if immunizing with gE protein fragments could produce antibodies
      that bind by the F(ab')(2) domain to gE and block the FcgammaR, as measured by
      competitively inhibiting nonimmune human IgG binding to the FcgammaR. Three gE
      peptides were constructed in baculovirus spanning almost the entire ectodomain
      and used to immunize mice and rabbits. Two fragments were highly effective at
      producing antibodies that bind by the F(ab')(2) domain and block the FcgammaR.
      The most potent of these two antibodies was far more effective at blocking the
      FcgammaR than antibodies that are only capable of binding by the Fc domains to
      the FcgammaR, including anti-gC, anti-gD, and nonimmune IgG. These results
      suggest that immunizing with gE fragments has potential for preventing immune
      evasion by blocking activities mediated by the HSV-1 FcgammaR.

PMID- 14963160
TI  - Modification to the capsid of the adenovirus vector that enhances dendritic cell
      infection and transgene-specific cellular immune responses.
AB  - Adenovirus (Ad) gene transfer vectors can be used to transfer and express
      antigens and function as strong adjuvants and thus are useful platforms for the
      development of genetic vaccines. Based on the hypothesis that Ad vectors with
      enhanced infectibility of dendritic cells (DC) may be able to evoke enhanced
      immune responses against antigens encoded by the vector in vivo, the present
      study analyzes the vaccine potential of an Ad vector expressing beta
      galactosidase as a model antigen and genetically modified with RGD on the fiber
      knob [AdZ.F(RGD)] to more selectively infect DC and consequently enhance immunity
      against the beta-galactosidase antigen. Infection of murine DC in vitro with
      AdZ.F(RGD) showed an eightfold-increased transgene expression following infection
      compared to AdZ (also expressing beta-galactosidase, but with a wild-type
      capsid). Binding, cellular uptake, and trafficking in DC were also increased with
      AdZ.F(RGD) compared to AdZ. To determine whether AdZ.F(RGD) could evoke enhanced
      immune responses to beta-galactosidase in vivo, C57BL/6 mice were immunized with
      AdZ.F(RGD) or AdZ subcutaneously via the footpad. Humoral responses with both
      vectors were comparable, with similar anti-beta-galactosidase antibody levels
      following vector administration. However, cellular responses to beta
      galactosidase were significantly enhanced, with the frequency of CD4(+) as well
      as the CD8(+) beta-galactosidase-specific gamma interferon response in cells
      isolated from the draining lymph nodes increased following immunization with
      AdZ.F(RGD) compared to Ad.Z (P < 0.01). Importantly, this enhanced cellular
      immune response of the AdZ.F(RGD) vector was sufficient to evoke enhanced
      inhibition of the growth of preexisting tumors expressing beta-galactosidase:
      BALB/c mice implanted with the CT26 syngeneic beta-galactosidase-expressing colon
      carcinoma cell line and subsequently immunized with AdZ.F(RGD) showed decreased
      tumor growth and improved survival compared to mice immunized with AdZ. These
      data demonstrate that addition of an RGD motif to the Ad fiber knob increases the
      infectibility of DC and leads to enhanced cellular immune responses to the Ad
      transferred transgene, suggesting that the RGD capsid modification may be useful
      in developing Ad-based vaccines.

PMID- 14963161
TI  - Extraepitopic compensatory substitutions partially restore fitness to simian
      immunodeficiency virus variants that escape from an immunodominant cytotoxic-T
      lymphocyte response.
AB  - Selection for escape mutant immunodeficiency viruses by cytotoxic T lymphocytes
      (CTL) has been well characterized and may be associated with disease progression.
      CTL epitopes accrue escape mutations at different rates in vivo. Interestingly,
      certain high-frequency CTL do not select for escape until the chronic phase of
      infection. Here we show that mutations conferring escape from immunodominant CTL
      directed against an epitope in the viral Gag protein are strongly associated with
      extraepitopic mutations in gag in vivo. The extraepitopic mutations partially
      restore in vitro replicative fitness of viruses bearing the escape mutations.
      Constraints on epitope sequences may therefore play a role in determining the
      rate of escape from CTL responses in vivo.

PMID- 14963162
TI  - Tat protein of human immunodeficiency virus type 1 subtype C strains is a
      defective chemokine.
AB  - Human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is
      correlated with increased monocyte migration to the brain, and the incidence of
      HAD among otherwise asymptomatic subjects appears to be lower in India than in
      the United States and Europe (1 to 2% versus 15 to 30%). Because of the genetic
      differences between HIV-1 strains circulating in these regions, we sought to
      identify viral determinants associated with this difference. We targeted Tat
      protein for these studies in view of its association with monocyte chemotactic
      function. Analyses of Tat sequences representing nine subtypes revealed that at
      least six amino acid residues are differentially conserved in subtype C Tat (C
      Tat). Of these, cysteine (at position 31) was highly (>99%) conserved in non
      subtype C viruses and more than 90% of subtype C viruses encoded a serine. We
      hypothesized a compromised chemotactic function of C-Tat due to the disruption of
      CC motif and tested it with the wild type C-Tat (CS) and its two isogenic
      variants (CC and SC) derived by site-directed mutagenesis. We found that the CS
      natural variant was defective for monocyte chemotactic activity without a loss in
      the transactivation property. While the CC mutant is functionally competent for
      both the functions, in contrast, the SC mutant was defective in both. Therefore,
      the loss of the C-Tat chemotactic property may underlie the reduced incidence of
      HAD; although not presenting conclusive evidence, this study provides the first
      evidence for a potential epidemiologic phenomenon associated with biological
      differences in the subtype C viruses.

PMID- 14963163
TI  - Inflammatory cytokines inhibit Kaposi's sarcoma-associated herpesvirus lytic gene
      transcription in in vitro-infected endothelial cells.
AB  - The response of Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) to
      inflammatory cytokine treatment of experimentally infected endothelial cells was
      investigated. The cytokines inhibited spontaneous KSHV lytic gene expression but
      not the level of infection. The data suggest that if inflammatory cytokines
      present in KS lesions contribute to KSHV pathogenesis, they do so in part by
      promoting latent KSHV infection of the endothelial cells.

PMID- 14963164
TI  - Specific interaction of feline immunodeficiency virus surface glycoprotein with
      human DC-SIGN.
AB  - DC-SIGN, a specific C-type lectin expressed on dendritic cells, binds and
      transmits multiple strains of primate immunodeficiency viruses to susceptible
      cells. Here, we report that human DC-SIGN also captures feline immunodeficiency
      virus via high-affinity (1 nM), Ca(2+)-dependent, D-mannose-inhibited binding to
      the major envelope glycoprotein, gp95.

PMID- 14963165
TI  - Human immunodeficiency virus type 1 escapes from RNA interference-mediated
      inhibition.
AB  - Short-term assays have suggested that RNA interference (RNAi) may be a powerful
      new method for intracellular immunization against human immunodeficiency virus
      type 1 (HIV-1) infection. However, RNAi has not yet been shown to protect cells
      against HIV-1 in long-term virus replication assays. We stably introduced vectors
      expressing small interfering RNAs (siRNAs) directed against the HIV-1 genome into
      human T cells by retroviral transduction. We report here that an siRNA directed
      against the viral Nef gene (siRNA-Nef) confers resistance to HIV-1 replication.
      This block in replication is not absolute, and HIV-1 escape variants that were no
      longer inhibited by siRNA-Nef appeared after several weeks of culture. These RNAi
      resistant viruses contained nucleotide substitutions or deletions in the Nef gene
      that modified or deleted the siRNA-Nef target sequence. These results demonstrate
      that efficient inhibition of HIV-1 replication through RNAi is possible in stably
      transduced cells. Therefore, RNAi could become a realistic gene therapy approach
      with which to overcome the devastating effect of HIV-1 on the immune system.
      However, as is known for antiviral drug therapy against HIV-1, antiviral
      approaches involving RNAi should be used in a combined fashion to prevent the
      emergence of resistant viruses.

PMID- 14963166
TI  - Cryoelectron microscopy of mouse mammary tumor virus.
AB  - Cryoelectron microscopy of Mouse mammary tumor virus, a Betaretrovirus, provided
      information about glycoprotein structure and core formation. The virions showed
      the broad range of diameters typical of retroviruses. Betaretroviruses assemble
      cytoplasmically, so the broad size range cannot reflect the use of the plasma
      membrane as a platform for assembly.

PMID- 14963167
TI  - Requirement of a 12-base-pair TATT-containing sequence and viral lytic DNA
      replication in activation of the Kaposi's sarcoma-associated herpesvirus K8.1
      late promoter.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) K8.1 late promoter consists of a
      minimal 24-bp sequence, with a TATA-like, 12-bp promoter core, AATATTAAAGGG, and
      is active on a reporter only in butyrate-induced KSHV-infected cells. The
      activity of the K8.1 promoter can be enhanced (>15-fold) by the KSHV left-end
      lytic origin of DNA replication (oriLyt-L) sequence while providing inefficient
      replication of plasmid DNA and is inhibited by viral DNA replication inhibitors,
      suggesting that activation of the K8.1 promoter on the reporter is involved in
      KSHV lytic DNA replication largely by trans.

PMID- 14963168
TI  - Bovine papillomavirus replicative helicase E1 is a target of the ubiquitin ligase
      APC.
AB  - The papillomavirus E1 replicative helicase is essential for replication and
      maintenance of extrachromosomal viral genomes in infected cells. We previously
      found that the bovine papillomavirus E1 protein is a substrate of the ubiquitin
      dependent proteolytic pathway. Here we show that E1 is targeted for degradation
      by the anaphase-promoting complex (APC). Inhibition of APC activity by the
      specific inhibitor Emi1 or point mutations in the D-box and KEN-box motifs of E1
      stabilize the protein and increase viral DNA replication in both a cell-free
      system and in living cells. These findings involve APC as the ubiquitin ligase
      that controls E1 levels to maintain a constant low copy number of the viral
      genome during latent infection.

PMID- 14963169
TI  - Roles of the E6 and E7 proteins in the life cycle of low-risk human
      papillomavirus type 11.
AB  - Many important functions have been attributed to the high-risk human
      papillomavirus (HPV) E6 and E7 proteins, including binding and degradation of p53
      as well as interacting with Rb proteins. In contrast, the physiological roles of
      the low-risk E6 and E7 proteins remain unclear. Previous studies demonstrated
      that the high-risk E6 and E7 proteins also play roles in the productive life
      cycle by facilitating the maintenance of viral episomes (J. T. Thomas, W. G.
      Hubert, M. N. Ruesch, and L. A. Laimins, Proc. Natl. Acad. Sci. USA 96:8449-8454,
      1999). In order to determine whether low-risk E6 or E7 is similarly necessary for
      the stable maintenance of episomes, HPV type 11 (HPV-11) genomes that contained
      translation termination mutations in E6 or E7 were constructed. Upon transfection
      into normal human keratinocytes, genomes in which E6 function was abolished were
      unable to be maintained episomally. Transfection of genomes containing
      substitution mutations in amino acids conserved in high- and low-risk HPV types
      suggested that multiple protein domains are involved in this process. Examination
      of cells transfected with HPV-11 genomes in which E7 function was inhibited were
      found to exhibit a more complex phenotype. At the second passage following
      transfection, mutant genomes were maintained as episomes but at significantly
      reduced levels than in cells transfected with the wild-type HPV-11 genome. Upon
      further passage in culture, however, the episomal forms of these E7 mutant
      genomes quickly disappeared. These findings identify important new functions for
      the low-risk E6 and E7 proteins in the episomal maintenance of low-risk HPV-11
      genomes and suggest that they may act in a manner similar to that observed for
      the high-risk proteins.

PMID- 14963170
TI  - Binding of the 2F5 monoclonal antibody to native and fusion-intermediate forms of
      human immunodeficiency virus type 1 gp41: implications for fusion-inducing
      conformational changes.
AB  - We investigated how the broadly neutralizing monoclonal antibody 2F5 affects the
      human immunodeficiency virus type 1 envelope glycoprotein as it undergoes
      receptor-induced conformational changes and show that 2F5 binds both native and
      fusion-intermediate conformations, suggesting inhibition of a late step in virus
      entry. We also demonstrate conformational changes in the C heptad of gp41.

PMID- 14963171
TI  - Role of indoleamine-2,3-dioxygenase in alpha/beta and gamma interferon-mediated
      antiviral effects against herpes simplex virus infections.
AB  - Gamma interferon (IFN-gamma)-mediated indoleamine-2,3-dioxygenase (IDO) activity
      in human astrocytoma cells and in native astrocytes was found to be responsible
      for the inhibition of herpes simplex virus replication. The effect is abolished
      in the presence of excess amounts of L-tryptophan. Both IFN-alpha and IFN-beta
      restricted herpes simplex virus replication in both cell types, but (in contrast
      to the results seen with IFN-gamma) the addition of an excess amount of L
      tryptophan did not inhibit the induced antiviral effect.

PMID- 14963172
TI  - Identification of peptides that inhibit the DNA binding, trans-activator, and DNA
      replication functions of the human papillomavirus type 11 E2 protein.
AB  - Peptide antagonists of the human papillomavirus type 11 (HPV-11) E2-DNA
      association were identified using a filamentous bacteriophage random peptide
      library. Synthetic peptides antagonized the E2-DNA interaction, effectively
      blocked E2-mediated transcriptional activation of a reporter gene in cell
      culture, and inhibited E1-E2-mediated HPV-11 DNA replication in vitro. These
      peptides may prove to be useful tools for characterizing E2 function and for
      exploring the effectiveness of E2-inhibitor-based treatments for HPV-associated
      diseases.

PMID- 14963173
TI  - Jaagsiekte sheep retrovirus envelope efficiently pseudotypes human
      immunodeficiency virus type 1-based lentiviral vectors.
AB  - Jaagsiekte sheep retrovirus (JSRV) infects lung epithelial cells in sheep, and
      oncoretroviral vectors bearing JSRV Env can mediate transduction of human cells,
      suggesting that such vectors might be useful for lung-directed gene therapy. Here
      we show that JSRV Env can also efficiently pseudotype a human immunodeficiency
      virus type 1-based lentiviral vector, a more suitable vector for transduction of
      slowly dividing lung epithelial cells. We created several chimeric Env proteins
      that, unlike the parental Env, do not transform rodent fibroblasts but are still
      capable of pseudotyping lentiviral and oncoretroviral vectors.

PMID- 14963174
TI  - Contribution of disulfide bridging to epitope expression of the dengue type 2
      virus envelope glycoprotein.
AB  - The individual contributions of each of the six conserved disulfide (SS) bonds in
      the dengue 2 virus envelope (E) glycoprotein (strain 16681) to epitope expression
      was determined by measuring the reactivities of a panel of well-defined
      monoclonal antibodies (MAbs) with LLC-MK(2) cells that had been transiently
      transformed with plasmid vectors expressing E proteins that were mutant in their
      SS bonds. Three domain I (DI) epitopes (C1, C3, and C4) were affected by
      elimination of any SS bond and were essentially the only epitopes affected by
      elimination of the amino-proximal SS1 formed between Cys 3 and Cys 30. The
      remaining DI epitope (C2) was sensitive to only SS3-bond (Cys 74-Cys 105) and SS6
      bond (Cys 302-Cys 333) elimination. Of the four DII epitopes examined,
      reactivities of three anti-epitope MAbs (A1, A2, and A5) were reduced by
      elimination of SS2 (Cys 61-Cys 121), SS3, SS4 (Cys 94-Cys 116), SS5 (Cys 185-Cys
      285), or SS6. The other DII epitope examined (A3) was sensitive only to SS2- and
      SS3-bond elimination. The three DIII epitopes tested (B2, B3, and B4) were most
      sensitive to elimination of SS6. The flavivirus group epitope (A1) was less
      sensitive to elimination of SS3 and SS6. This result may indicate that the region
      proximal to the E-protein fusion motif (amino acids 98 to 110) may have important
      linear components. If this observation can be confirmed, peptide mimics from this
      region of E protein might be able to interfere with flavivirus replication.

PMID- 14963175
TI  - Credentials for uterine artery embolization.

PMID- 14963177
TI  - Patient care and uterine artery embolization for leiomyomata.

PMID- 14963178
TI  - The chemistry of acrylic bone cements and implications for clinical use in image
      guided therapy.
AB  - Advances in image-guided therapy for vertebral fractures and other bone-related
      disorders have made acrylic bone cement an integral part of the interventional
      armamentarium. Unfortunately, information on the properties and chemistry of
      these compounds is mostly published in the biomaterial sciences literature, a
      source with which the interventional community is generally unfamiliar. This
      review focuses on the chemistry of bone cement polymerization and the properties
      of components in polymethylmethacrylate (PMMA)-based polymers, the most commonly
      used bone cements in interventional procedures such as percutaneous
      vertebroplasty. The effects of altering the concentration of components such as
      methylmethacrylate monomers, PMMA beads, benzoyl peroxide activator, N,N-dimethyl
      p-toluidine (DMPT) initiator, and radiopacifiers on the setting time,
      polymerization temperature, and compressive strength of the cement are also
      considered. This information will allow interventional radiologists to manipulate
      bone cement characteristics for specific applications and maximize the clinical
      potential of image-guided interventions.

PMID- 14963179
TI  - 2004 SIR Annual Meeting film panel cases.

PMID- 14963180
TI  - The effect of initial shunt outflow position on patency of transjugular
      intrahepatic portosystemic shunts.
AB  - PURPOSE: It has been suggested that initial stent position in transjugular
      intrahepatic portosystemic shunts (TIPS) with relation to hepatic venous outflow
      is an important determinant of shunt patency. It was hypothesized that TIPS with
      the stent-implanted segments terminating in the hepatic vein (HV) have shorter
      primary unassisted shunt patency durations than TIPS with the stent-implanted
      segments extending to the hepatocaval junction. MATERIALS AND METHODS: A
      consecutive group of 107 patients who underwent TIPS creation for variceal
      bleeding were retrospectively identified, and the angiographic images during
      initial TIPS creation were reviewed independently by two observers who were
      blinded to outcome. Primary unassisted patency was estimated in group A (TIPS
      terminating in the HV; n = 47) and group B (TIPS terminating at the hepatocaval
      junction; n = 60) with the Kaplan-Meier method, and the two groups were compared
      with the log-rank test. Patients who had less than 30 days of follow-up were
      excluded from the analysis. RESULTS: Among all 107 patients, primary unassisted
      patency rates at 3, 6, and 12 months were 91% +/- 4%, 74% +/- 6%, and 49% +/- 6%.
      TIPS were classified into group A or group B with high interobserver agreement
      (Cohen kappa = 0.98). At 12 months, the primary unassisted patency rate among the
      patients in group A was 36% +/- 10%, compared with 58% +/- 8% among the patients
      in group B (P =.017, log-rank test). Patients in group A were twice as likely to
      lose patency than patients in group B (95% CI of odds ratio, 1.2-4.5). Thirty-day
      mortality was similar between groups (15% vs 12%; P =.13). CONCLUSION: Initial
      stent position within the hepatic venous outflow is predictive of shunt patency,
      with TIPS extending to the hepatocaval junction having a longer lifespan than
      shunts terminating in the HV.

PMID- 14963181
TI  - Embolotherapy of pulmonary arteriovenous malformations: efficacy of platinum
      versus stainless steel coils.
AB  - PURPOSE: To compare the results of embolotherapy of pulmonary arteriovenous
      malformations (PAVMs) with use of platinum versus stainless-steel coils.
      MATERIALS AND METHODS: From a database of 78 consecutive patients with PAVMs
      treated by embolotherapy between May 1992 and September 2001, 54 patients with
      306 PAVMs were selected for retrospective evaluation. Exclusion criteria were
      PAVMs with less than 12 months of follow-up computed tomography (CT) of the
      thorax (n = 15), embolotherapy with a mixture of embolic materials (n = 8), and
      repeat embolotherapy for previous treatment failures (n = 1). Successful
      treatment was defined as complete resolution of the aneurysm sac and draining
      vein on follow-up CT (all patients) and/or absence of contrast material flow
      through the PAVM on pulmonary angiography (n = 27). RESULTS: Of 267 PAVMs
      embolized with stainless-steel coils, 249 (93.3%) were successfully occluded
      (mean follow-up, 3.1 years). Of 39 PAVMs embolized with platinum coils, 35
      (89.7%) were successfully occluded (mean follow-up, 2.1 years). There was no
      significant difference in success between the two groups (P =.5). The mean
      feeding artery size was significantly larger (P <.0001) in the platinum group
      (4.3 mm) than in the stainless-steel group (3.5 mm). Potentially serious
      complications included coil reflux (n = 3), PAVM perforation (n = 2), self
      limited neurologic deficit (n = 2), and systemic embolization of a coil (n = 1)
      in the stainless-steel group, and PAVM perforation (n = 2) in the platinum group.
      There were no long-term sequelae. CONCLUSIONS: Coil embolotherapy is highly
      efficacious, with no statistically significant difference between platinum and
      stainless-steel coils. The slightly higher proportion of sustained occlusion with
      stainless-steel coils may be partly explained by the larger mean feeding artery
      size in the platinum group. The study is limited by the small sample size of the
      platinum group.

PMID- 14963182
TI  - Transthoracic image-guided biopsy of lung nodules: when is benign really benign?
AB  - PURPOSE: A pathologic diagnosis of malignancy by image-guided transthoracic fine
      needle aspiration (FNA) with or without (+/-) core biopsy is definitive. However,
      a benign diagnosis of a lung nodule by FNA +/- core biopsy presents a management
      dilemma of resection for confirmation versus follow-up imaging and/or medical
      treatment. We propose three separate pathologic categories of benign diagnosis
      after FNA +/- core biopsy: (i) benign specific (ie, aspergillosis); (ii) benign
      nonspecific (ie, fibrosis); and (iii) nondiagnostic. Our goal was to define when
      to resect "benign" nodules to avoid an unacceptably high false-negative rate.
      MATERIALS AND METHODS: All FNA +/- core biopsy diagnoses considered nonmalignant
      at a single institution from 1996 to 2001 were retrospectively reviewed for
      management and outcomes by radiologic or pathologic follow-up. RESULTS: Ninety
      five of 836 total cases with FNA +/- core biopsies over the 5-year period were
      identified as nonmalignant and had complete pathologic or radiologic follow-up.
      Twenty-one of 95 had a benign specific diagnosis; all were true-negative for
      malignancy on radiologic (n = 17) or surgical (n = 4) follow-up. The remaining 74
      had either benign nonspecific (n = 53) or nondiagnostic (n = 21) diagnoses. Seven
      of 53 benign nonspecific specimens (13%) and six of 21 nondiagnostic specimens
      (29%) were malignant at excisional biopsy or radiologic follow-up. Sixteen of 95
      (17%) had a postprocedural pneumothorax requiring a chest tube. CONCLUSION:
      Transthoracic FNA +/- core biopsy may yield a nonmalignant diagnosis as (i)
      benign specific, (ii) benign nonspecific, or (iii) nondiagnostic. Diagnosis
      directed medical management is recommended for a benign specific diagnosis.
      Additional diagnostic studies, repeat biopsy, or resection is necessary for
      benign nonspecific and nondiagnostic biopsy results as a result of an
      unacceptably high rate of malignancy.

PMID- 14963183
TI  - Realtime digital magnification of the fluoroscopic and digital subtraction
      angiography images: randomized prospective study to show dose reduction during
      segmental chemoembolization for hepatocellular carcinoma.
AB  - PURPOSE: To show efficacy of realtime digital magnification of fluoroscopic and
      digital subtraction angiography images for dose reduction both of the medical
      personnel and the patient during segmental chemoembolization for hepatocellular
      carcinoma. MATERIALS AND METHODS: Thirty patients were randomized into two
      groups; chemoembolization was performed with digital magnification (group A; n =
      15) or with shorter field of view (group B; n = 15). Dose area product was used
      as a convenient and reasonable analog of the patient dose. Medical personnel dose
      and dose area product were compared. RESULTS: Medical personnel dose and dose
      area product were 7.0 +/- 3.4 micro Sv and 71060 +/- 24653 cGy. cm(2)in group A,
      and 21.4 +/- 16.2 micro Sv and 110379 +/- 48065 cGy. cm(2) in group B,
      respectively. There were statistically significant differences in both the
      medical personnel dose (P =.002, Student t test) and the dose area product (P
      =.009, Student t test). CONCLUSION: Digital magnification decreased the medical
      personnel dose by 67% and the patient dose by 36% during segmental
      chemoembolization for hepatocellular carcinoma.

PMID- 14963184
TI  - Clot lysis in a primate model of peripheral arterial occlusive disease with use
      of systemic or intraarterial reteplase: addition of abciximab results in improved
      vessel reperfusion.
AB  - PURPOSE: This study was designed to compare the ability of reteplase (a
      fibrinolytic agent) alone or in combination with abciximab (a monoclonal antibody
      antagonist of platelet glycoprotein IIb/IIIa) to achieve and sustain vessel
      patency in an acute model of peripheral arterial occlusive disease in cynomolgus
      monkeys. MATERIALS AND METHODS: Total arterial occlusion was induced in the
      femoral arteries of 32 cynomolgus monkeys (eight groups of four) by endothelial
      injury and injection of thrombin-treated autologous blood. Reteplase was
      administered by intravenous bolus dose or by intraarterial infusion at the site
      of the clot. Abciximab was administered as a single weight-adjusted intravenous
      bolus dose. Platelet activity was measured by ex vivo platelet aggregation before
      and after abciximab treatment. Different groups of animals received sequential
      partial doses of reteplase with or without increasing doses of abciximab until
      either the weight-adjusted human dose equivalent of reteplase was reached or
      vessel recanalization was achieved. RESULTS: Animals receiving reteplase-only
      regimens demonstrated variability in the times required for reperfusion and the
      permanence of the effect. The coadministration of abciximab at doses of the
      antibody that achieved near or full inhibition of platelet function generally
      decreased the time to reperfusion and resulted in more consistent and sustained
      vessel patency. In the case of systemic intravenous reteplase, the
      coadministration of abciximab resulted in effective reperfusion of thrombosed
      vessels at decreased doses of the lytic agent. CONCLUSIONS: Reteplase
      administered systemically or at the site of thrombotic occlusion restored blood
      flow for periods of varying duration in monkeys with acute femoral artery
      thrombosis. The coadministration of systemic intravenous abciximab to intravenous
      or intraarterial reteplase allowed the use of lower doses of fibrinolytic agent
      with more accelerated and sustained reperfusion.

PMID- 14963185
TI  - Percutaneous transgastric technique for creating gastroenteric anastomoses in
      swine.
AB  - PURPOSE: To develop a percutaneous transgastric procedure for creating a stent
      containing gastroenteric anastomosis (GEA). MATERIALS AND METHODS: Acute
      experiments were performed on eight pigs. A 10-F gastroduodenostomy sheath was
      used to insert guide wires and targeting devices in the retrogastric jejunal
      loop; a 6.5-F sheathed trocar needle was then introduced through a second gastric
      sheath to puncture and catheterize the jejunum through the back of the stomach.
      Two special sliding anchor pairs were introduced through the catheter to
      "sandwich" the gastric sheath to the jejunal wall. The jejunum was catheterized a
      third time between the anchor sets to create a GEA tract for insertion of a
      stent. The animals were killed at various periods as long as 1 month after the
      experiments. RESULTS: Snares were the most useful targeting devices for jejunal
      puncture. Single (n = 1) and double (n = 7) anchor-pair staples effectively
      prevented intraperitoneal leakage during and after insertion of 12-mm or 14-mm
      stents. Necropsy of six healthy animals at 5 days, 7 days, 14 days, and 4 weeks
      (n = 3) showed well-developed patent GEA anastomoses. There was one anesthetic
      death; one animal was killed at 4 days for obstructive ileus after a difficult
      transgastric jejunal catheterization. CONCLUSIONS: A GEA can be fashioned through
      a percutaneous gastrostomy with stapling anchors. This technique may have
      clinical applications for managing gastric outlet obstruction.

PMID- 14963187
TI  - Radiofrequency cauterization with biopsy introducer needle.
AB  - PURPOSE: The principal risks of needle biopsy are hemorrhage and implantation of
      tumor cells in the needle tract. This study compared hemorrhage after liver and
      kidney biopsy with and without radiofrequency (RF) ablation of the needle tract.
      MATERIALS AND METHODS: Biopsies of liver and kidney were performed in swine
      through introducer needles modified to allow RF ablation with the distal 2 cm of
      the needle. After each biopsy, randomization determined whether the site was to
      undergo RF ablation during withdrawal of the introducer needle. Temperature was
      measured with a thermistor stylet near the needle tip, with a target temperature
      of 70 degrees C-100 degrees C with RF ablation. Blood loss was measured as grams
      of blood absorbed in gauze at the puncture site for 2 minutes after needle
      withdrawal. Selected specimens were cut for gross examination. RESULTS: RF
      ablation reduced bleeding compared with absence of RF ablation in liver and
      kidney (P <.01), with mean blood loss reduced 63% and 97%, respectively. Mean
      amounts of blood loss (+/-SD) in the liver in the RF and no-RF groups were 2.03 g
      +/- 4.03 (CI, 0.53-3.54 g) and 5.50 g +/- 5.58 (CI, 3.33-7.66 g), respectively.
      Mean amounts of blood loss in the kidney in the RF and no-RF groups were 0.26 g
      +/- 0.32 (CI, -0.01 to 0.53 g) and 8.79 g +/- 7.72 (CI, 2.34-15.24 g),
      respectively. With RF ablation, thermal coagulation of the tissue surrounding the
      needle tract was observed. CONCLUSION: RF ablation of needle biopsy tracts
      reduced hemorrhage after biopsy in the liver and kidney and may reduce
      complications of hemorrhage as well as implantation of tumor cells in the tract.

PMID- 14963188
TI  - Magnetic resonance-guided placement of aortic stents grafts: feasibility with
      real-time magnetic resonance fluoroscopy.
AB  - PURPOSE: The artifact behavior of different aortic stent-grafts was evaluated
      with real-time magnetic resonance (MR) imaging, and the feasibility of real-time
      MR-guided stent-graft placement in the abdominal aorta was tested. MATERIALS AND
      METHODS: Seven different stent-grafts and their deployment systems were analyzed
      in an in vitro setting regarding their artifacts on different real-time MR images
      with cartesian, spiral, and radial k-space filling. The device and the real-time
      sequence with the fewest artifacts were used for an in vivo study in a swine
      model. In four animals, a straight aortic stent-graft was placed in the
      infrarenal abdominal aorta under real-time MR guidance. Results were controlled
      with MR angiography, multislice spiral computed tomography, and digital
      subtraction angiography. RESULTS: The in vitro study proved only one of the seven
      stent grafts (including deployment systems) to be suitable for real-time MR
      guided intervention. MR-guided placement of the stent-grafts was possible in all
      animals. In one animal, the stent-graft dislocated during withdrawal of the
      deployment system as a result of a mismatch between stent-graft diameter and size
      of the infrarenal aorta. CONCLUSION: Real-time MR-guided placement of stent
      grafts in the abdominal aorta with use of commercially available standard
      instruments is feasible. However, for clinical use, dedicated devices and
      deployment systems producing less artifacts are required.

PMID- 14963189
TI  - Fatal pulmonary complications after arterial embolization with 40-120- micro m
      tris-acryl gelatin microspheres.
AB  - Hepatic arterial embolization is a recognized method of treating primary
      malignancies and some secondary hepatic malignancies. Particle embolization alone
      has been shown to be safe and effective and is routinely performed for
      hypervascular tumors. Tris-acryl gelatin microspheres have been widely acclaimed
      for their ease of delivery and uniform size, allowing for accurate targeting of
      particular end arteries. There have been three deaths at the author's institution
      related to respiratory compromise since the 40-120- micro m particles became
      available 31 months ago. These complications were never observed with larger tris
      acryl gelatin microspheres or polyvinyl alcohol particles. This is an unusual and
      serious complication of which interventionalists performing embolotherapy need to
      be aware.

PMID- 14963192
TI  - Re: Endovenous laser treatment of saphenous vein reflux: long-term results.

PMID- 14963190
TI  - Covered stent placement in a traumatically injured vertebral artery.

PMID- 14963199
TI  - Folate supplementation and methotrexate treatment in rheumatoid arthritis: a
      review.
AB  - OBJECTIVES: The folate antagonist methotrexate (MTX) has become established as
      the most commonly used disease-modifying anti-rheumatic drug (DMARD) in the
      treatment of rheumatoid arthritis (RA) but is commonly discontinued due to
      adverse effects. Adverse effects are thought to be mediated via folate
      antagonism. In this paper we summarize the current data on the use of folates as
      a supplement to MTX use in RA for the prevention of adverse effects and as a
      potential modulator of cardiovascular risk, and propose guidelines for standard
      practice. METHODS: A Medline search was performed using the search terms
      "methotrexate", "folic acid", "folinic acid", "folate" and "homocysteine".
      Literature relevant to the use of folates as a supplement to MTX in the treatment
      of RA was reviewed and other papers referred to as references were explored.
      RESULTS: The use of supplemental folates, including folic and folinic acid, in RA
      patients treated with MTX has been shown to improve continuation rates by
      reducing the incidence of liver function test abnormalities and gastrointestinal
      intolerance. Folate supplements do not appear to significantly reduce the
      effectiveness of MTX in the treatment of RA. Furthermore, supplemental folic acid
      offsets the elevation in plasma homocysteine associated with the use of MTX. This
      may in turn reduce the risk of cardiovascular disease, which is over-represented
      amongst patients with RA, and for which hyperhomocysteinaemia is now recognized
      as an independent risk factor. CONCLUSIONS: We propose that folic acid
      supplements be prescribed routinely to all patients receiving MTX for the
      treatment of RA. We recommend a pragmatic dosing schedule of 5 mg of oral folic
      acid given on the morning following the day of MTX administration.

PMID- 14963200
TI  - Maintenance of remission with leflunomide in Wegener's granulomatosis.
AB  - OBJECTIVE: To investigate the safety and efficacy of leflunomide plus low-dose
      prednisolone for the maintenance of remission in Wegener's granulomatosis (WG).
      METHODS: This was a Phase II, single-centre, open-label clinical investigation of
      patients with generalized WG treated with leflunomide after the induction of
      complete (n = 4) or partial (n = 16) remission by cyclophosphamide/prednisolone
      combination therapy. Leflunomide treatment was initiated at 20 mg/day and
      increased to 30 mg/day after 12 weeks and, in patients with partial remission, to
      40 mg/day after 24 weeks. Concomitant low-dose prednisolone (< or =10 mg/day) was
      allowed during the study. In addition to the frequency of relapse, treatment
      efficacy was assessed by the standard measures of disease activity/extent.
      RESULTS: A total of 20 patients were enrolled in the trial. During a treatment
      period of up to 2.5 yr (median 1.75 yr, range 1-2.5 yr), one patient had a major
      relapse and required retreatment with cyclophosphamide/prednisolone. Eight
      patients had minor relapses that were successfully treated by dose increases to
      40 mg/day leflunomide. Disease activity remained unchanged for the duration of
      the study. The most frequently reported adverse events were mild respiratory
      infection (40%), arthralgia (35%) and hypertension (35%); dry skin, nail disorder
      and diarrhoea were each reported by 30% of patients. Despite the aggressive
      pretreatment with cyclophosphamide, adverse events with leflunomide treatment at
      the higher dose (30-40 mg/day) were comparable with those seen with the standard
      dose (20 mg/day) for rheumatoid arthritis patients. CONCLUSION: Leflunomide
      appears to be safe and well tolerated for the maintenance of complete or partial
      remission of WG. The results of this pilot study encourage further controlled
      trials comparing leflunomide with alternative remission maintenance therapies.

PMID- 14963201
TI  - Longitudinal study of the relationship between knee angle and tibiofemoral
      cartilage volume in subjects with knee osteoarthritis.
AB  - OBJECTIVES: There is emerging evidence that knee alignment is associated with
      progression of osteoarthritis (OA). The aim of this study was to examine the
      relationship between baseline knee angle and the rate of cartilage loss in
      subjects with knee OA. METHODS: One hundred and seventeen subjects with knee OA
      had standing radiographs and MRI on their symptomatic knee at baseline and at the
      1.9+/-0.2 yr follow-up. Knee cartilage volume was measured at baseline and follow
      up. Knee angle was defined as the angle subtended by a line drawn through the mid
      shaft of the femur with respect to one drawn through the mid-shaft of the tibia.
      RESULTS: At baseline, in the medial compartment, as the angle decreased (i.e. was
      less varus) the tibial and femoral cartilage volume increased. In the lateral
      compartment, as the angle became more valgus, there was a reduction in tibial and
      femoral cartilage volume. In the longitudinal study, for every 1 degrees increase
      in baseline varus angulation there was an average annual loss of medial femoral
      cartilage of 17.7 micro l [95% confidence interval (CI) 6.5-28.8]. Although not
      statistically significant, there was a trend for a similar relationship between
      loss of medial tibial cartilage volume and baseline knee angle. In the lateral
      compartment, there was an average loss of tibial cartilage volume of 8.0 micro l
      (95% CI 0.0-16.0) for every 1 degrees increase in valgus angle. CONCLUSIONS:
      Baseline knee angle is associated with the rate of cartilage loss in the knee.
      Further work will be needed to determine whether therapies aimed at modifying the
      knee angle will reduce the progression of knee OA.

PMID- 14963202
TI  - Are evidence-based guidelines being followed for the monitoring of ocular
      toxicity of hydroxychloroquine? A nationwide survey of practice amongst
      consultant rheumatologists and implications for clinical governance.
AB  - OBJECTIVE: To determine whether consultant rheumatologists monitor the ocular
      toxicity of hydroxychloroquine according to standards set by national guidelines.
      METHOD: An observational cross-sectional questionnaire study of all consultant
      rheumatologists in the UK was undertaken. The main outcome measure was the
      proportion of rheumatologists who practise in compliance with nationally set
      standards. RESULTS: A wide variation in practice was found. Nearly half the
      respondents did not assess either baseline visual symptoms or visual acuity, and
      3% undertook infrequent visual monitoring at intervals of longer than 1 yr. At
      least a quarter of rheumatologists within the survey routinely referred patients
      to ophthalmology, either for baseline visual screening or for regular visual
      monitoring. Such use of ophthalmology services was outside the recommendations of
      the guidelines and would suggest that these referrals were unnecessary. No
      differences in monitoring practices were ascertained between respondents from
      district general and teaching hospitals. CONCLUSION: The present study shows that
      nationally set guidelines for the monitoring of ocular toxicity of
      hydroxychloroquine are not consistently followed by rheumatologists with regard
      to baseline assessment, referral to ophthalmology and frequency of monitoring.
      Clinical guidelines aim to reduce variations in practice and to promote uniform
      and consistent best practice. The present study demonstrates a lack of conformity
      to national guidelines in respect of the monitoring of ocular toxicity of
      hydroxychloroquine. Clinical governance provides a framework for assuring quality
      in health care. The implications of this study for clinical governance would
      include understanding why barriers to the use of guidelines might occur and how
      they might be overcome, risk management, accounting for the reasonableness of a
      decision for positive divergence and audit.

PMID- 14963203
TI  - Systemic lupus erythematosus and gouty arthritis: an uncommon association.
AB  - OBJECTIVE: To examine the frequency of gouty arthritis in patients with systemic
      lupus erythematosus (SLE) and elucidate the clinical factors that predispose to
      this occurrence. METHODS: A chart review of in-patients (1989-2001) and out
      patients (1999-2001) with ICD9 billing codes for gouty arthritis/tophaceous gout
      and SLE was performed. Twenty-six patients were identified. Patients meeting
      American College of Rheumatism criteria for SLE and crystal-proven gout or a self
      limited inflammatory arthritis felt to be crystal-induced (i.e. definite gout)
      were included. RESULTS: Ten patients were identified. Their mean age was 46.5 yr;
      80% were African-American and 70% were women. Nine of the ten had lupus nephritis
      and four had undergone renal transplantation. An acute worsening of renal
      function unrelated to lupus activity preceded almost all gout flares. Lupus
      activity at the time of the first gout attack as measured by the Systemic Lupus
      Activity Measure (SLAM) was low. Eight patients were on prednisone (mean dose 8
      mg/day) for their SLE at the time the attack of gout occurred. CONCLUSIONS: Gouty
      arthritis is uncommon in SLE; it occurs primarily in patients with long-standing
      SLE and nephritis. Worsening renal function usually preceded gout attacks, but
      SLE disease activity was minimal. Crystal-induced arthritis should be included in
      the differential diagnosis of a lupus patient presenting with acute inflammatory
      arthritis because the long-term treatment of the two conditions differs
      substantially.

PMID- 14963204
TI  - Lupus nephritis: treatment with mycophenolate mofetil.
AB  - OBJECTIVE: To evaluate the safety and efficacy of mycophenolate mofetil (MMF)
      treatment in patients with lupus nephritis. METHODS: Eighteen patients with
      biopsy-proven lupus nephritis (17 females, one male; mean age 31.6 yr; mean lupus
      duration 92 months; mean duration of nephritis 57 months; nine with focal
      proliferative glomerulonephritis, three with diffuse proliferative
      glomerulonephritis, six with membranous nephropathy) were included. With five
      exceptions, all patients had been treated previously with cyclophosphamide and
      were selected because of either toxicity or inadequate clinical response to
      treatment. MMF was given at 2 g daily in combination with steroids for up to 31
      months (mean 15.3 months). The side-effects of MMF were recorded and efficacy was
      assessed as the renal function profile. RESULTS: Complete remission was observed
      in 10/18 patients and another 4/18 went into partial remission. Both creatinine
      clearance and proteinuria were significantly improved during MMF treatment in
      patients with the proliferative forms of nephritis. MMF demonstrated a steroid
      sparing effect in the whole population. Treatment failure was recorded in 4/18
      patients, all with membranous nephropathy. Two patients developed
      gastrointestinal complaints and infectious meningitis occurred in one patient.
      CONCLUSION: MMF appears to be an efficacious and safe treatment in patients with
      proliferative forms of lupus nephritis who do not respond to or cannot tolerate
      conventional treatment. The efficacy of MMF in lupus membranous nephropathy
      remains unclear.

PMID- 14963205
TI  - The Devonshire Royal Hospital Buxton.

PMID- 14963206
TI  - Does giving osteoporosis patient information to women who have had a fracture
      improve access to health care?

PMID- 14963207
TI  - Joint examination skills: are rheumatology specialist registrars adequately
      trained?

PMID- 14963208
TI  - Jo-1 syndrome with associated poorly differentiated adenocarcinoma.

PMID- 14963209
TI  - Visual loss from optic neuropathy in dermatomyositis.

PMID- 14963210
TI  - Primary synovial non-Hodgkin's lymphoma in association with ankylosing
      spondylitis.

PMID- 14963211
TI  - Vitamin D deficiency in a patient with systemic lupus erythematosus.

PMID- 14963212
TI  - Failure of infliximab treatment and occurrence of erythema nodosum during therapy
      in two patients with Behcet's disease.

PMID- 14963215
TI  - Statins and lupus erythematosus.

PMID- 14963213
TI  - Osteoprotegerin and receptor activator of nuclear factor kappaB ligand expression
      in fibroblast-like synoviocytes from rheumatoid arthritis and osteoarthritis
      patients.

PMID- 14963217
TI  - UK guidelines on management of Paget's disease of bone.

PMID- 14963219
TI  - Anti-tumour necrosis factor therapy in the West Midlands.

PMID- 14963220
TI  - Association of birth weight with osteoporosis and osteoarthritis in adult twins.

PMID- 14963227
TI  - PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent
      circadian oscillations in mouse peripheral tissues.
AB  - Mammalian circadian rhythms are regulated by the suprachiasmatic nucleus (SCN),
      and current dogma holds that the SCN is required for the expression of circadian
      rhythms in peripheral tissues. Using a PERIOD2::LUCIFERASE fusion protein as a
      real-time reporter of circadian dynamics in mice, we report that, contrary to
      previous work, peripheral tissues are capable of self-sustained circadian
      oscillations for >20 cycles in isolation. In addition, peripheral organs
      expressed tissue-specific differences in circadian period and phase.
      Surprisingly, lesions of the SCN in mPer2(Luciferase) knockin mice did not
      abolish circadian rhythms in peripheral tissues, but instead caused phase
      desynchrony among the tissues of individual animals and from animal to animal.
      These results demonstrate that peripheral tissues express self-sustained, rather
      than damped, circadian oscillations and suggest the existence of organ-specific
      synchronizers of circadian rhythms at the cell and tissue level.

PMID- 14963232
TI  - Neurons arise in the basal neuroepithelium of the early mammalian telencephalon:
      a major site of neurogenesis.
AB  - Neurons of the mammalian CNS are thought to originate from progenitors dividing
      at the apical surface of the neuroepithelium. Here we use mouse embryos
      expressing GFP from the Tis21 locus, a gene expressed throughout the neural tube
      in most, if not all, neuron-generating progenitors, to specifically reveal the
      cell divisions that produce CNS neurons. In addition to the apical, asymmetric
      divisions of neuroepithelial (NE) cells that generate another NE cell and a
      neuron, we find, from the onset of neurogenesis, a second population of
      progenitors that divide in the basal region of the neuroepithelium and generate
      two neurons. Basal progenitors are most frequent in the telencephalon, where they
      outnumber the apically dividing neuron-generating NE cells. Our observations
      reconcile previous data on the origin and lineage of CNS neurons and show that
      basal, rather than apical, progenitors are the major source of the neurons of the
      mammalian neocortex.

PMID- 14963236
TI  - Pathogenicity and immunogenicity of influenza viruses with genes from the 1918
      pandemic virus.
AB  - The 1918 influenza A H1N1 virus caused the worst pandemic of influenza ever
      recorded. To better understand the pathogenesis and immunity to the 1918 pandemic
      virus, we generated recombinant influenza viruses possessing two to five genes of
      the 1918 influenza virus. Recombinant influenza viruses possessing the
      hemagglutinin (HA), neuraminidase (NA), matrix (M), nonstructural (NS), and
      nucleoprotein (NP) genes or any recombinant virus possessing both the HA and NA
      genes of the 1918 influenza virus were highly lethal for mice. Antigenic analysis
      by hemagglutination inhibition (HI) tests with ferret and chicken H1N1 antisera
      demonstrated that the 1918 recombinant viruses antigenically most resembled
      A/Swine/Iowa/30 (Sw/Iowa/30) virus but differed from H1N1 viruses isolated since
      1930. HI and virus neutralizing (VN) antibodies to 1918 recombinant and
      Sw/Iowa/30 viruses in human sera were present among individuals born before or
      shortly after the 1918 pandemic. Mice that received an intramuscular immunization
      of the homologous or Sw/Iowa/30-inactivated vaccine developed HI and VN
      antibodies to the 1918 recombinant virus and were completely protected against
      lethal challenge. Mice that received A/PR/8/34, A/Texas/36/91, or A/New
      Caledonia/20/99 H1N1 vaccines displayed partial protection from lethal challenge.
      In contrast, control-vaccinated mice were not protected against lethal challenge
      and displayed high virus titers in respiratory tissues. Partial vaccine
      protection mediated by baculovirus-expressed recombinant HA vaccines suggest
      common cross-reactive epitopes on the H1 HA. These data suggest a strategy of
      vaccination that would be effective against a reemergent 1918 or 1918-like virus.

PMID- 14963238
TI  - Mapping knowledge domains: characterizing PNAS.
AB  - A review of data mining and analysis techniques that can be used for the mapping
      of knowledge domains is given. Literature mapping techniques can be based on
      authors, documents, journals, words, and/or indicators. Most mapping questions
      are related to research assessment or to the structure and dynamics of
      disciplines or networks. Several mapping techniques are demonstrated on a data
      set comprising 20 years of papers published in PNAS. Data from a variety of
      sources are merged to provide unique indicators of the domain bounded by PNAS. By
      using funding source information and citation counts, it is shown that, on an
      aggregate basis, papers funded jointly by the U.S. Public Health Service (which
      includes the National Institutes of Health) and non-U.S. government sources
      outperform papers funded by other sources, including by the U.S. Public Health
      Service alone. Grant data from the National Institute on Aging show that, on
      average, papers from large grants are cited more than those from small grants,
      with performance increasing with grant amount. A map of the highest performing
      papers over the 20-year period was generated by using citation analysis. Changes
      and trends in the subjects of highest impact within the PNAS domain are
      described. Interactions between topics over the most recent 5-year period are
      also detailed.

PMID- 14963244
TI  - PICKLE acts throughout the plant to repress expression of embryonic traits and
      may play a role in gibberellin-dependent responses.
AB  - A seed marks the transition between two developmental states; a plant is an
      embryo during seed formation, whereas it is a seedling after emergence from the
      seed. Two factors have been identified in Arabidopsis that play a role in
      establishment of repression of the embryonic state: PKL (PICKLE), which codes for
      a putative CHD3 chromatin remodeling factor, and gibberellin (GA), a plant growth
      regulator. Previous observations have also suggested that PKL mediates some
      aspects of GA responsiveness in the adult plant. To investigate possible
      mechanisms by which PKL and GA might act to repress the embryonic state, we
      further characterized the ability of PKL and GA to repress embryonic traits and
      reexamined the role of PKL in mediating GA-dependent responses. We found that PKL
      acts throughout the seedling to repress expression of embryonic traits. Although
      the ability of pkl seedlings to express embryonic traits is strongly induced by
      inhibiting GA biosynthesis, it is only marginally responsive to abscisic acid and
      SPY (SPINDLY), factors that have previously been demonstrated to inhibit GA
      dependent responses during germination. We also observed that pkl plants exhibit
      the phenotypic hallmarks of a mutation in a positive regulator of a GA response
      pathway including reduced GA responsiveness and increased synthesis of bioactive
      GAs. These observations indicate that PKL may mediate a subset of GA-dependent
      responses during shoot development.

PMID- 14963245
TI  - Ascorbate-deficient mutants of Arabidopsis grow in high light despite chronic
      photooxidative stress.
AB  - Acclimation to changing environments, such as increases in light intensity, is
      necessary, especially for the survival of sedentary organisms like plants. To
      learn more about the importance of ascorbate in the acclimation of plants to high
      light (HL), vtc2, an ascorbate-deficient mutant of Arabidopsis, and the double
      mutants vtc2npq4 and vtc2npq1 were tested for growth in low light and HL and
      compared with the wild type. The vtc2 mutant has only 10% to 30% of wild-type
      levels of ascorbate, vtc2npq4 has lower ascorbate levels and lacks non
      photochemical quenching of chlorophyll fluorescence (NPQ) because of the absence
      of the photosystem II protein PsbS, and vtc2npq1 is NPQ deficient and also lacks
      zeaxanthin in HL but has PsbS. All three genotypes were able to grow in HL and
      had wild-type levels of Lhcb1, cytochrome f, PsaF, and 2-cysteine peroxiredoxin.
      However, the mutants had lower electron transport and oxygen evolution rates and
      lower quantum efficiency of PSII compared with the wild type, implying that they
      experienced chronic photooxidative stress. The mutants lacking NPQ in addition to
      ascorbate were only slightly more affected than vtc2. All three mutants had
      higher glutathione levels than the wild type in HL, suggesting a possible
      compensation for the lower ascorbate content. These results demonstrate the
      importance of ascorbate for the long-term acclimation of plants to HL.

PMID- 14963246
TI  - Gibberellins repress photomorphogenesis in darkness.
AB  - Plants undergo two different developmental programs depending on whether they are
      growing in darkness (skotomorphogenesis) or in the presence of light
      (photomorphogenesis). It has been proposed that the latter is the default pathway
      followed by many plants after germination and before the seedling emerges from
      soil. The transition between the two pathways is tightly regulated. The conserved
      COP1-based complex is central in the light-dependent repression of
      photomorphogenesis in darkness. Besides this control, hormones such as
      brassinosteroids (BRs), cytokinins, auxins, or ethylene also have been shown to
      regulate, to different extents, this developmental switch. In the present work,
      we show that the hormone gibberellin (GA) widely participates in this regulation.
      Studies from Arabidopsis show that both chemical and genetic reductions of
      endogenous GA levels partially derepress photomorphogenesis in darkness. This is
      based both on morphological phenotypes, such as hypocotyl elongation and hook and
      cotyledon opening, and on molecular phenotypes, such as misregulation of the
      light-controlled genes CAB2 and RbcS. Genetic studies indicate that the GA
      signaling elements GAI and RGA participate in these responses. Our results also
      suggest that GA regulation of this response partially depends on BRs. This
      regulation seems to be conserved across species because lowering endogenous GA
      levels in pea (Pisum sativum) induces full de-etiolation in darkness, which is
      not reverted by BR application. Our results, therefore, attribute an important
      role for GAs in the establishment of etiolated growth and in repression of
      photomorphogenesis.

PMID- 14963247
TI  - Editorial.

PMID- 14963248
TI  - Low back pain interventions at the workplace: a systematic literature review.
AB  - OBJECTIVE: To assess the effect of controlled workplace interventions on low back
      pain (LBP) through a review of controlled studies. The rising costs of employees
      with LBP have resulted in an abundance of offers to society and organizations of
      interventions to prevent and/or treat the problem. Little is known of the effect
      of the different interventions. METHODS: A systematic literature search based on
      the inclusion criteria: controlled trial, work setting and assessment of at least
      one of the four main outcome measures: sick leave; costs; new episodes of LBP;
      and pain. Effect of the interventions was reported for the four main outcome
      measures. RESULTS: Thirty-one publications from 28 interventions were found to
      comply with the inclusion criteria. Exercise interventions to prevent LBP among
      employees and interventions to treat employees with LBP have documented an effect
      on sick leave, costs and new episodes of LBP. Multidisciplinary interventions
      have documented an effect on the level of pain. CONCLUSIONS: The results show
      that there is good reason to be careful when considering interventions aiming to
      prevent LBP among employees. Of all the workplace interventions only exercise and
      the comprehensive multidisciplinary and treatment interventions have a documented
      effect on LBP. There is a need for studies employing good methodology.

PMID- 14963249
TI  - Continuing professional development of occupational medicine practitioners: a
      needs assessment.
AB  - OBJECTIVE: The aim of this study was to identify elements of occupational
      medicine practice used on a frequent basis which are considered to be of high
      priority for continuing professional development (CPD). METHODS: A postal
      questionnaire covering 28 areas of knowledge or practice was sent to all members
      of the Society of Occupational Medicine in September 2000. Respondents were asked
      to allocate scores to the 28 items for both CPD priority and frequency of use.
      RESULTS: The return rate for questionnaires was 29.5%. There was reasonable
      agreement between frequency of use and CPD priority ratings for the elements
      covered in the questionnaire. CONCLUSIONS: Despite the low return rate for
      questionnaires, this survey has helped identify themes which are important to
      physicians practising occupational medicine and has also highlighted those which
      are less important for inclusion in a CPD programme. Some differences in
      responses were identified between accredited specialists, specialist registrars
      and non-specialist practitioners of occupational medicine. The findings from this
      survey should be useful to providers of continuing medical education in planning
      courses, study days and electronic or distance learning educational packages.

PMID- 14963250
TI  - Preventing baker's asthma: an alternative strategy.
AB  - BACKGROUND: Although baker's asthma has attracted considerable research interest
      over the last 30 years, success in its prevention has been slow to achieve. This
      paper describes the results of an alternative preventive strategy, based on an
      observation that the excess of sensitization in bread bakers is largely due to
      IgE-mediated allergy to fungal amylase, contained in bread improvers. The
      practical application of the strategy has been to limit bread improver exposures
      to <1 mg/m3 [8 h time-weighted average (TWA)], whilst exposures to all other
      ingredients, including flour, have been limited to <10 mg/m3 (8 h TWA). METHOD:
      The paper describes the findings of in-house respiratory health surveillance and
      dust sampling programmes, from a UK food company whose primary interests are
      milling and baking, over the period following the introduction of the strategy to
      target the reduction in bread improver exposure. RESULTS: Over the 10 year period
      of surveillance, the incidence of symptomatic sensitization in the bread baking
      sector (2240 per million employees per annum) was greater than for the other
      flour-using groups (330 per million employees per annum), despite broadly similar
      total inhalable dust exposures. There was an overall reduction in the incidence
      of new cases of symptomatic sensitization, from 2085 per million employees per
      year in the first 5 years of the surveillance programme, to 405 per million
      employees per year in the subsequent 5 years. CONCLUSION: The strategy of
      targeting bread improver exposure is an effective approach for the prevention of
      new cases of symptomatic sensitization in bread bakeries.

PMID- 14963252
TI  - Psychological workload and body weight: is there an association? A review of the
      literature.
AB  - BACKGROUND: According to Karasek's Demand/Control Model, workload can be
      conceptualized as job strain, a combination of psychological job demands and
      control in the job. High job strain may result from high job demands combined
      with low job control. Aim To give an overview of the literature on the
      association between obesity and psychological workload. METHOD: We carried out a
      review of the associations between psychological workload and body weight in men
      and women. In total, 10 cross-sectional studies were identified. RESULTS: The
      review showed little evidence of a general association between psychological
      workload and body mass index. Only weak positive associations were found, and
      only between elements of psychological workload and overall body weight. For body
      fat distribution, two out of three studies showed a positive association in men,
      but the associations became insignificant after adjustment for education. For
      women, there was no evidence of a consistent association. CONCLUSION: The
      reviewed articles were not supportive of any associations between psychological
      workload and either general or abdominal obesity. Future epidemiological studies
      in this field should be prospective or experimental, and should examine how
      chronic work stress affects eating and to what extent initial body weight is a
      predictor for individual differences in perceived psychological workload.

PMID- 14963251
TI  - Mortality of workers at a plant manufacturing nickel alloys, 1958-2000.
AB  - BACKGROUND: Excess risks of respiratory cancer have been demonstrated in some
      groups of nickel-exposed workers. It is clear, however, that not all forms of
      nickel exposure are implicated in these excess risks. Aim To determine whether
      occupational exposures received in the manufacture of nickel alloys lead to
      increased risks of cancer, in particular nasal cancer and lung cancer. METHODS:
      The mortality experienced by a cohort of 1999 workers employed at a plant
      manufacturing nickel alloys has been investigated. Study subjects were all those
      male workforce employees first employed in the period 1953-1992 who had at least
      5 years employment with the company. Observed numbers of cause-specific deaths
      were compared with expectations based on national mortality rates. Standardized
      mortality ratios (SMRs) were calculated by period from commencing employment and
      by operating area of first job. In addition, rate ratios derived from Poisson
      regression and based on an internal standard were calculated by levels of
      duration of employment. RESULTS: SMRs were significantly below 100 for all causes
      (observed 557, expected 704.3, SMR 79), all neoplasms (observed 169, expected
      209.4, SMR 81) non-malignant diseases of the respiratory system (observed 50,
      expected 73.0, SMR 69) and diseases of the circulatory system (observed 261,
      expected 335.5, SMR 78). Significantly elevated SMRs were not shown for any cause
      of death and mortality was below expectation for stomach cancer (observed 8,
      expected 16.0, SMR 50), lung cancer (observed 64, expected 73.6, SMR 87) and
      bladder cancer (observed 3, expected 8.0, SMR 38). There were no deaths from
      nasal cancer (expected 0.33). More detailed findings were unexceptional.
      CONCLUSIONS: The analyses did not suggest the presence of an occupational cancer
      hazard in the mortality experience of the cohort.

PMID- 14963253
TI  - Occupational exposure and health problems in small-scale industry workers in Dar
      es Salaam, Tanzania: a situation analysis.
AB  - BACKGROUND: Workers in informal small-scale industries (SSI) in developing
      countries involved in welding, spray painting, woodwork and metalwork are exposed
      to various hazards with consequent risk to health. Aim To assess occupational
      exposure and health problems in SSI in Dar es Salaam, Tanzania. METHODS: Focused
      group discussions (FGD) were conducted among SSI workers. Participants were
      assessed for exposure to occupational and environmental hazards, the use of
      protective equipment and health complaints by interview. The findings were
      discussed with participants and potential interventions identified. RESULTS:
      Three hundred and ten workers were interviewed (response rate 98%). There was a
      high level (>90%) of self-reported exposure to either dust, fumes, noise or
      sunlight in certain occupational groups. There was low reported use of personal
      protective equipment. There was a high level of self-reported occupational health
      problems, particularly amongst welders and metalworkers. Workers reported their
      needs as permanent workplaces, information on work related hazards, water and
      sanitation, and legislation for SSI. CONCLUSIONS: In SSI in Tanzania, our study
      suggests that workers have high levels of exposure to multiple health hazards and
      that use of protective equipment is poor. This group of workers warrants improved
      occupational health and safety provision.

PMID- 14963254
TI  - Early retirement: does cause of invalidity influence rate of social security
      benefit processing in Zimbabwe?
AB  - BACKGROUND: The social security invalidity benefit programme in Zimbabwe is
      organized through a network of regional offices. There are no standard guidelines
      for assessing invalidity. Aim We tested whether cause of invalidity and place of
      residence influenced the rate of processing of invalidity benefit claims. METHOD:
      We carried out a retrospective cohort study involving 523 medically unadjudicated
      and a 25% (354/1431) random sample of medically adjudicated invalidity benefit
      claims at the Central Benefits Office of the National Social Security Authority
      in Zimbabwe. The outcome for the study was time from certification of invalidity
      to conclusion of medical adjudication of invalidity benefit claims. RESULTS:
      Compared with tuberculosis, HIV disease increased the rate of progress to final
      medical adjudication 2.6-fold, musculoskeletal diseases 1.9-fold, physical
      injuries 1.7-fold and chronic diseases 1.8-fold after adjusting for place of
      residence, industrial sector, gender and age. Compared with residing in Harare,
      residing in Chinhoyi, Gweru, Masvingo and Mutare regions reduced the rate of
      progress to final medical adjudication by 62, 69, 51 and 56%, respectively, after
      adjusting for cause of invalidity, industrial sector, gender and age. Compared
      with invalidity benefit claims from the services sector, those from the mining
      sector experienced a 45% reduction in rate of progress to final medical
      adjudication after adjusting for cause of invalidity, place of residence, gender
      and age. CONCLUSION: Cause of invalidity, place of residence and industrial
      sector had significant influences on the rate of progress to final medical
      adjudication of invalidity benefit claims.

PMID- 14963255
TI  - Relationship between self-reported low productivity and overtime working.
AB  - OBJECTIVE: To investigate the relationship between overtime working and self
      reported low productivity due to poor health over the course of 1 year. METHODS:
      The subjects were 94 random-sampled workers at a Japanese manufacturing company.
      The data on sickness absence and low productivity due to poor health were
      collected by self-report questionnaires every month from October 1999 to
      September 2000. Seventy-four workers returned complete answers. The complete data
      on overtime hours of forty-nine of these employees were obtained from company
      records. RESULTS: In those reporting low productivity, cold-like symptoms and
      sleep loss were given as the causes. Low productivity was closely linked to
      overtime worked, whereas sick leave tended to increase during periods of change
      in overtime working. CONCLUSION: Our results suggest the possibility of a
      relationship between overtime working and self-reported low productivity.

PMID- 14963256
TI  - Musculoskeletal disorders in hotel restaurant workers.
AB  - BACKGROUND: A variety of occupational groups have been shown to experience
      elevated risks of work-related musculoskeletal disorders (WMSD). Little
      information on WMSD is available in hotel restaurant workers. OBJECTIVE: To
      document the profile of WMSD in a sample of hotel restaurant workers in Taiwan.
      METHODS: A self-administered questionnaire was used to gather information
      regarding body site specific WMSD, pain intensity and strategies for pain relief
      amongst a sample of hotel restaurant workers. RESULTS: Among 905 restaurant
      workers, 785 (84%) reported experience of WMSD in the previous month, with the
      highest prevalence rate found for the shoulder (58%). The highest mean score for
      perceived pain intensity was found for the lower back/waist (2.50 points).
      Despite a high prevalence rate, only a small portion of those reporting WMSD
      (12%) considered their work capacity or activities of daily living to be affected
      by WMSD, and only <5% of workers with WMSD sought medical treatment. CONCLUSION:
      WMSD related pain is common among hotel restaurant workers in Taiwan, but it does
      not appear to interfere with job performance or daily living. Self-treatment and
      alternative therapies that have not been evaluated for effectiveness are commonly
      employed by hotel restaurant workers.

PMID- 14963257
TI  - Do occupational stress management programmes affect absenteeism rates?

PMID- 14963258
TI  - Re: Lawson IJ, McGeoch KL. A medical assessment process for a large volume of
      medico-legal compensation claims for hand-arm vibration syndrome.

PMID- 14963260
TI  - Monitor.

PMID- 14963261
TI  - Kinetic and thermodynamic characterization of the RNA-cleaving 8-17
      deoxyribozyme.
AB  - The 8-17 deoxyribozyme is a small DNA catalyst of significant applicative
      interest. We have analyzed the kinetic features of a well behaved 8-17 construct
      and determined the influence of several reaction conditions on such features,
      providing a basis for further exploration of the deoxyribozyme mechanism. The 8
      17 bound its substrate with a rate constant approximately 10-fold lower than
      those typical for the annealing of short complementary oligonucleotides. The
      observed free energy of substrate binding indicates that an energetic penalty
      near to +7 kcal/mol is attributable to the deoxyribozyme core. Substrate cleavage
      required divalent metal ion cofactors, and the dependence of activity on the
      concentration of Mg2+, Ca2+ or Mn2+ suggests the occurrence of a single, low
      specificity binding site for activating ions. The efficiency of activation
      correlated with the Lewis acidity of the ion cofactor, compatible with a metal
      assisted deprotonation of the reactive 2'-hydroxyl group. However, alternative
      roles of the metal ions cannot be excluded, because those ions that are stronger
      Lewis acids are also capable of forming stronger interactions with ligands such
      as the phosphate oxygens. The apparent enthalpy of activation for the 8-17
      reaction was close to the values observed for hydroxide-catalyzed and hammerhead
      ribozyme-catalyzed RNA cleavage.

PMID- 14963262
TI  - Statistical analysis of over-represented words in human promoter sequences.
AB  - The identification and characterization of regulatory sequence elements in the
      proximal promoter region of a gene can be facilitated by knowing the precise
      location of the transcriptional start site (TSS). Using known TSSs from over 5700
      different human full-length cDNAs, this study extracted a set of 4737 distinct
      putative promoter regions (PPRs) from the human genome. Each PPR consisted of
      nucleotides from -2000 to +1000 bp, relative to the corresponding TSS. Since many
      regulatory regions contain short, highly conserved strings of less than 10
      nucleotides, we counted eight-letter words within the PPRs, using z-scores and
      other related statistics to evaluate their over- and under-representation.
      Several over-represented eight-letter words have known biological functions
      described in the eukaryotic transcription factor database TRANSFAC; however, many
      did not. Besides calculating a P-value with the standard normal approximation
      associated with z-scores, we used two extra statistical controls to evaluate the
      significance of over-represented words. These controls have important
      implications for evaluating over- and under-represented words with z-scores.

PMID- 14963263
TI  - A mutation in polynucleotide phosphorylase from Escherichia coli impairing RNA
      binding and degradosome stability.
AB  - Polynucleotide phosphorylase (PNPase), a 3' to 5' exonuclease encoded by pnp,
      plays a key role in Escherichia coli RNA decay. The enzyme, made of three
      identical 711 amino acid subunits, may also be assembled in the RNA degradosome,
      a heteromultimeric complex involved in RNA degradation. PNPase autogenously
      regulates its expression by promoting the decay of pnp mRNA, supposedly by
      binding at the 5'-untranslated leader region of an RNase III-processed form of
      this transcript. The KH and S1 RNA-binding domains at the C-terminus of the
      protein (amino acids 552-711) are thought to be involved in pnp mRNA recognition.
      Here we show that a G454D substitution in E.coli PNPase impairs autogenous
      regulation whereas it does not affect the catalytic activities of the enzyme.
      Although the mutation maps outside of the KH and S1 RNA-binding domains, analysis
      of the mutant protein revealed a defective RNA binding, thus suggesting that
      other determinants may be involved in PNPase-RNA interactions. The mutation also
      caused a looser association with the degradosome and an abnormal electrophoretic
      mobility in native gels. The latter feature suggests an altered structural
      conformation of PNPase, which may account for the properties of the mutant
      protein.

PMID- 14963265
TI  - The ACCESS study.

PMID- 14963266
TI  - Familial intracranial aneurysms.

PMID- 14963267
TI  - Patent foramen ovale and stroke: closure by further randomized trial is required!

PMID- 14963268
TI  - Patent foramen ovale and recurrent stroke: closure is the best option: no.

PMID- 14963269
TI  - Patent foramen ovale and recurrent stroke: closure is the best option: yes.

PMID- 14963270
TI  - Gene therapy and endovascular treatment of intracranial aneurysms.
AB  - BACKGROUND: Endovascular treatment of intracranial aneurysms is safe and
      effective but too often is followed by recurrences. Gene therapy may improve
      healing after embolization, and endovascular approaches may offer future in situ
      delivery systems designed to prevent aneurysm rupture. SUMMARY OF REVIEW:
      Advances in coil technology have focused on coating strategies designed to modify
      the biological reaction to the embolic agent. Gene therapy in cardiovascular
      applications is limited by low efficiency and transient gene expression. Current
      advances include the potential use of circulating progenitor cells for ex vivo
      genetic manipulations followed by in vivo delivery. Direct gene transfer may also
      be enhanced in situ by coils carrying antibody-tethered adenovirus or through the
      use of cell-specific or radiation-inducible promoters. Candidate genes that may
      be of value in promoting healing after endovascular treatment include growth
      factors and metalloproteinase inhibitors. A better understanding of the biology
      of aneurysm is necessary to conceive strategies designed to control the
      development of these lesions before their rupture. CONCLUSIONS: Many technical
      difficulties remain to be solved, but the combination of gene therapy and
      endovascular techniques offers multiple therapeutic possibilities in the future
      control of intracranial aneurysms.

PMID- 14963271
TI  - Glucose but not lactate in combination with acidosis aggravates ischemic neuronal
      death in vitro.
AB  - BACKGROUND AND PURPOSE: Hyperglycemia aggravates brain damage in clinical stroke
      and in experimental in vivo models of cerebral ischemia. Elevated preischemic
      glucose levels, lactate production, and intracerebral acidosis correlate with
      increased brain damage. We have developed a murine hippocampal slice culture
      model of in vitro ischemia (IVI), suitable for studies of the mechanisms of
      neuronal death. In this model we investigated the individual contribution of
      glucose, pH, lactate, and combinations thereof as well as ionotropic glutamate
      receptor activation to the development of hyperglycemic ischemic cell death.
      METHODS: Murine organotypic hippocampal slice cultures were exposed to IVI in a
      medium with an ionic composition similar to that of the extracellular fluid in
      the brain during ischemia in vivo. Cell death was assessed by propidium iodide
      uptake. Ionotropic glutamate receptor blockade was accomplished by D-2-amino-5
      phosphonopentanoic acid (D-APV) or 2,3-dihydro-6-nitro-7-sulfamoyl
      benzo(F)quinoxaline (NBQX). RESULTS: The combination of high glucose levels and
      acidosis (pH 6.8), but not acidosis per se or the combination of lactate and
      acidosis during IVI, exacerbated damage. Cell death after hyperglycemic IVI was
      not diminished by blockade of ionotropic glutamate receptors. CONCLUSIONS:
      Aggravation of brain damage by hyperglycemia in vivo can be reproduced in
      hippocampal slice cultures in vitro. Our results demonstrate that glucose per se,
      but not lactate, in combination with acidosis mediates the detrimental
      hyperglycemic effect through a mechanism independent of ionotropic glutamate
      receptors.

PMID- 14963272
TI  - Determinants of handicap after stroke: the North East Melbourne Stroke Incidence
      Study (NEMESIS).
AB  - BACKGROUND AND PURPOSE: Handicap, although more relevant to the patient than
      impairment or disability, has received little attention in people with stroke.
      The aim of this study was to identify, in an unselected population, factors
      determining handicap at 2 years after stroke. METHODS: All first-ever cases of
      stroke in a population of 306 631 over a 1-year period were assessed. Stroke
      severity, comorbidity, and demographic information was recorded. Among survivors,
      2-year poststroke handicap was assessed with the London Handicap Scale.
      Disability, physical impairment, depression, anxiety, living arrangements, and
      recurrent stroke at 2 years were documented. If necessary, proxy assessments were
      obtained, except for mood. Linear regression analyses were performed to identify
      factors independently associated with handicap. First, all assessments (proxy and
      nonproxy) were examined; then, the nonproxy assessments were used to examine the
      effects of mood. RESULTS: Of 266 patients with incident stroke who were alive at
      2 years, 226 (85%) were assessed. Significant determinants of handicap on
      univariable analysis were age, female sex, socioeconomic status, alcohol intake,
      stroke subtype, initial stroke severity; 2-year physical impairment, disability,
      depression and anxiety scores; institutionalization; and recurrent stroke. On
      multivariable analysis, the independent determinants of handicap were age and 2
      year physical impairment and disability. In analysis restricted to nonproxy data,
      depression and anxiety were also independently associated with handicap.
      CONCLUSIONS: Age, concurrent disability, and physical impairment were more
      important determinants of handicap than other demographic factors or initial
      stroke severity. Because depression and anxiety were independently associated
      with handicap, their treatment may potentially reduce handicap in stroke
      patients.

PMID- 14963273
TI  - Silent brain infarcts in patients with manifest vascular disease.
AB  - BACKGROUND AND PURPOSE: Silent infarcts are frequently found on MRIs of brains of
      healthy elderly persons (aged >60 years). The purpose of this study was to
      investigate the prevalence and determinants of silent infarcts in a population of
      patients with clinically manifest vascular disease. METHODS: To detect silent
      infarcts, MR images were made in 308 participants of the Second Manifestations of
      ARTerial disease (SMART) study (mean age, 58 years) without prior stroke or
      transient ischemic attack. These are patients referred to the University Medical
      Center Utrecht because of atherosclerotic vascular disease. Risk factors were
      assessed by questionnaire and by physical, ultrasonographic, and laboratory
      examinations. RESULTS: Silent infarcts were found in 51 patients (17%). Most
      infarcts (62%) were located in white matter, 20% in basal ganglia, 14% in brain
      stem and cerebellum, and 4% in cortical area. Categorical determinants for
      presence of silent infarct(s) that remained (borderline) significant after
      adjustment for age were hypertension (odds ratio [OR]=2.2; 95% CI, 1.2 to 4.2),
      abdominal aortic aneurysm (OR=2.4; 95% CI, 0.9 to 6.4), severe renal failure
      (OR=7.3; 95% CI, 2.1 to 25.2), and hyperhomocysteinemia (OR=2.6; 95% CI, 1.1 to
      5.9). CONCLUSIONS: Patients with manifest vascular disease are at risk for silent
      infarcts at a younger age. In particular, patients with the aforementioned risk
      factors should be considered for treatment or (secondary) prevention.

PMID- 14963274
TI  - Lateral and medial medullary infarction: a comparative analysis of 214 patients.
AB  - BACKGROUND AND PURPOSE: No large-scale study has ever compared the clinical and
      radiological features of lateral medullary infarction (LMI) and medial medullary
      infarction (MMI). The aim of this study was to investigate them through the use
      of cooperatively collected cases. METHODS: Medical information on all patients
      from 1996 to 2000 with medullary infarction (MI) proven by brain MR images at 35
      stroke centers in the Tohoku district, Japan, was collected, and their clinical
      and radiological features were analyzed. RESULTS: A total of 214 cases of MI were
      registered. They included 167 cases (78%) of LMI, 41 (19%) of MMI, and 6 (3%) of
      LMI plus MMI. The mean age of onset and the male-to-female ratio were 60.7 years
      and 2.7:1 in LMI and 65.0 years and 3.6:1 in MMI, respectively. The middle
      medulla was most frequently affected in LMI, and the upper medulla was most
      frequently affected in MMI. Dissection of the vertebral artery was observed in
      29% of LMI and 21% of MMI. Prognosis, assessed by the Barthel Index, was
      favorable in both LMI and MMI. Diabetes mellitus was more frequently associated
      with MMI than with LMI. CONCLUSIONS: The present study surveyed a large number of
      MI cases and revealed that (1) the mean age of onset of MMI is higher than that
      of LMI, (2) the dissection of the vertebral artery is an important cause not only
      of LMI but also of MMI, and (3) diabetes mellitus is frequently associated with
      MMI.

PMID- 14963275
TI  - Rasch analysis of combining two indices to assess comprehensive ADL function in
      stroke patients.
AB  - BACKGROUND AND PURPOSE: To justify the summation of scores representing
      comprehensive activities of daily living (ADL) function, a Rasch analysis was
      performed to examine whether items of the Barthel Index (BI), assessing ADL, and
      items of the Frenchay Activities Index (FAI), assessing instrumental ADL,
      contribute jointly to a single, unidimensional construct in stroke patients
      living in the community. The number of scoring points of both indices was
      examined for their usefulness in discerning the various ability levels of ADL in
      these patients. METHODS: A total of 245 patients at 1 year after stroke
      participated in this study. The BI and FAI were administered to the patient
      and/or the patient's main caregiver by interview. RESULTS: The initial Rasch
      analysis indicated that the middle scoring points for many items of the BI and
      FAI could be collapsed to allow only dichotomous response categories. All but 2
      items of the FAI, social occasions and walking outside, fitted the model's
      expectations rather well. These 2 items were excluded from further analysis. A
      factor analysis performed on the residuals of the Rasch-transformed scores
      recovered no dominant component. These results indicate that the combined 23
      dichotomous items of the BI and FAI assess a single unidimensional ADL function.
      CONCLUSIONS: A clinically useful assessment of the comprehensive ADL function of
      patients at or later than 1 year after stroke can be obtained by combining the
      items of the BI and FAI (excluding 2 FAI items) and simplifying the responses
      into dichotomous categories. It is also demonstrated that the items of the new
      scale measure comprehensive ADL function as a single unidimensional construct
      when assessed at 1 year after stroke.

PMID- 14963276
TI  - Value of routine holter monitoring for the detection of paroxysmal atrial
      fibrillation in patients with cerebral ischemic events.
AB  - BACKGROUND AND PURPOSE: Holter monitoring for the detection of paroxysmal atrial
      fibrillation (PAF) is a routine procedure after cerebral ischemic events,
      although its value is unknown. The aim of this study was to evaluate the
      incidence of PAF and its impact on drug treatment modifications in this
      population. METHODS: Retrospective evaluation of all Holter ECGs in patients with
      cerebral ischemic events was done. Chart analysis with regard to drug treatment
      modification and cardiovascular drug therapy was performed in all patients.
      RESULTS: Between January 2000 and December 2002, 425 hospitalized patients
      (median age, 68 years) had routine Holter ECG after a cerebral ischemic event.
      PAF was diagnosed in 9 patients (2.1%): in 2, oral anticoagulation was
      contraindicated; 1 had severe carotid stenosis as an additional risk factor; 1
      had PAF but was on oral anticoagulation for basilar thrombosis; 2 had had PAF
      before and were on aspirin; and 3 had a new diagnosis of PAF. The last 5 patients
      were put on oral anticoagulation. Thus, routine Holter ECG resulted in drug
      treatment modification in only 5 of 425 patients (1.2%). CONCLUSIONS: PAF in
      cerebral ischemic event patients has a low incidence and, if diagnosed, rarely
      leads to drug modification. Therefore, routine Holter monitoring for PAF
      screening is not recommended in this patient population.

PMID- 14963277
TI  - Endothelial nitric oxide gene haplotypes and risk of cerebral small-vessel
      disease.
AB  - BACKGROUND AND PURPOSE: Genetic influences are important in multifactorial
      cerebral small-vessel disease (SVD) and may act via endothelial dysfunction.
      Nitric oxide (NO) synthesized by endothelial nitric oxide synthase (eNOS) is a
      key mediator of endothelial function. We determined the role of 3 potentially
      functional eNOS polymorphisms (T-786C, intron 4ab, G894T) located toward the 5'
      flanking end of the gene as risk factors for SVD and different SVD subtypes:
      isolated lacunar infarction (n=137) and ischemic leukoaraiosis (n=160). METHODS:
      Three hundred patients with SVD and 600 community controls were studied.
      Genotypes were determined through polymerase chain reaction with or without
      restriction fragment digestion. Nitrate (NO(x)) levels were determined in a
      subgroup by use of a Griess method. Polymorphisms were tested individually and in
      combination with haplotype analysis. RESULTS: The intron 4a variant was
      protective against SVD. This effect was confined to isolated lacunar infarction
      (odds ratio, 0.55; 95% confidence interval, 0.35 to 0.86; P=0.01). Haplotypes
      encountered were significantly different in this subtype compared with controls
      (P=0.001), with the -786C promoter/intron 4a combination particularly
      underrepresented. NO(x) levels were associated with the T-786C locus (P=0.03) but
      only in the presence of the intron 4a allele (P=0.07 for interaction).
      CONCLUSIONS: The intron 4ab insertion/deletion genotype was associated with
      isolated lacunar infarction. Haplotype and functional studies suggested that the
      protective effect of the 4a variant could be mediated through changes in eNOS
      promoter activity and increased NO levels. The specific association with isolated
      symptomatic lacunar infarction and not ischemic leukoaraiosis may reflect
      different etiopathogeneses of the 2 subtypes. Lack of NO could predispose to
      localized microatheroma in proximal arterioles rather than diffuse
      arteriosclerosis affecting distal perforating vessels.

PMID- 14963278
TI  - Lesion location and poststroke depression: systematic review of the
      methodological limitations in the literature.
AB  - BACKGROUND: It has been hypothesized that poststroke depression (PSD) results
      from left hemisphere lesions. However, attempts to systematically review the data
      investigating lesion location and PSD have yielded conflicting results. We sought
      to investigate the methodological differences across the literature studying the
      relationship between lesion location and PSD. SUMMARY OF REVIEW: A MEDLINE
      literature search to retrieve articles investigating the association between PSD
      and lesion location was performed. Information sought included source population
      of samples, definition of depression, standardized measurement of stroke and
      depression, blinding, time since stroke onset, and study design. Odds ratios
      (ORs) and 95% CIs were calculated with the use of Review Manager and MetaView
      statistical software. Twenty-six original articles were reviewed. Much of the
      heterogeneity across studies reflected differences in methodology. The direction
      of association between left hemisphere lesion location and PSD varied depending
      on whether patients were sampled as inpatients (OR, 1.36; 95% CI, 1.05 to 1.76)
      or from the community (OR, 0.60; 95% CI, 0.39 to 0.92). Change in the direction
      of association was also observed across assessment interval from the acute stroke
      (OR, 2.14; 95% CI, 1.50 to 3.04) to the chronic stroke (OR, 0.53; 95% CI, 0.30 to
      0.93) phase. Differences in the measurement of depression, study design, and
      presentations of results also may have contributed to the heterogeneity of the
      findings. CONCLUSIONS: Several key initiatives should be addressed before future
      research is undertaken, including the development of a comprehensive measure of
      PSD, optimal poststroke assessment intervals, and determination of a
      representative population reference.

PMID- 14963279
TI  - Prehospital delay after acute stroke in Kaohsiung, Taiwan.
AB  - BACKGROUND AND PURPOSE: Successful acute stroke intervention depends on early
      hospital presentation. Our study aimed to examine the extent of and factors
      associated with prehospital delays after acute stroke in Taiwan, where people are
      new to thrombolytic therapy for stroke. METHODS: Data were prospectively
      collected from 196 patients admitted with acute stroke who presented to the
      emergency department (ED) of the study hospital within 48 hours of symptom onset
      before intravenous recombinant tissue plasminogen activator was approved.
      Prehospital delay was defined as time from symptom onset to the ED arrival.
      Univariate and multivariable regression analyses were conducted to evaluate
      factors influencing delay in ED presentation and delay in decision to seek
      medical help. RESULTS: The median interval between symptom onset and decision to
      seek medical contact was 90 minutes; the median interval between symptom onset
      and ED arrival was 335 minutes. The time from symptom onset to first call for
      medical help accounted for 45% (95% confidence interval, 41 to 50) of the
      prehospital delay. Advanced age delayed the decision to seek medical help,
      whereas stroke severity reduced the risk for this delay. CONCLUSIONS: The time
      interval between symptom onset and the decision to call for medical care is far
      from optimal and is the underlying cause of prolonged prehospital delay.
      Educational efforts to reduce extent of delay are urgently needed.

PMID- 14963280
TI  - Evolution of diaschisis in a focal stroke model.
AB  - BACKGROUND AND PURPOSE: Stroke produces diaschisis in adjacent and connected
      regions. The sequential changes in diaschisis over time and the relationship of
      regions of diaschisis to functional cortical areas and regions of poststroke
      neuroplasticity have not been determined. METHODS: Small cortical strokes were
      produced in the barrel cortex of rats. Relative glucose metabolism was determined
      in vivo over time with [18F]fluorodeoxyglucose small-animal positron emission
      tomography. Cerebral blood flow was measured with [14C]iodoantipyrine. Regions of
      hypometabolism and hypoperfusion were compared with histological damage in the
      same animals. RESULTS: Small cortical strokes produce an initial network of
      hypometabolism in a broad region of cortex adjacent to the stroke and in the
      striatum and thalamus on day 1. Cerebral blood flow is diminished only
      immediately around the cortical infarct on day 1. A substantial area of cortex
      adjacent to the stroke remains hypometabolic on day 8. This persistent cortical
      hypometabolism occupies the somatosensory cortex, forelimb motor cortex, and
      second somatosensory area. CONCLUSIONS: Focal stroke produces ipsilateral
      diaschisis in connected cortical regions that is clearly distant from subtotal
      damage and may play a role in poststroke neuroplasticity.

PMID- 14963282
TI  - Prevalence of stroke survivors in rural South Africa: results from the Southern
      Africa Stroke Prevention Initiative (SASPI) Agincourt field site.
AB  - BACKGROUND AND PURPOSE: The importance of stroke in low-income regions such as
      sub-Saharan Africa has recently been emphasized. However, little is known about
      the burden of stroke in sub-Saharan Africa. We investigated the prevalence of
      stroke survivors in the Agincourt Health and Population Unit, a demographic
      surveillance site in the rural northeast of South Africa. METHODS: Census workers
      asked household informants 2 screening questions for stroke during the annual
      census. If either question was answered positively, a clinician visited
      individuals aged > or =15 years to confirm the likely diagnosis of stroke. We
      performed a detailed assessment and defined stroke according to the World Health
      Organization criteria. RESULTS: A total of 42 378 individuals were aged > or =15
      years. There were 982 positive responses to the questionnaire, and we examined
      724 individuals (74%). We identified 103 strokes (crude prevalence, 243/100 000).
      After adjustment for those we did not examine, the prevalence was 300/100 000
      (95% CI, 250 to 357). Sixty-six percent of stroke survivors needed help with at
      least 1 activity of daily living (Segi age-standardized prevalence, 200/100 000).
      CONCLUSIONS: Stroke prevalence in rural South Africa is higher than previously
      documented in Africa but lower than in high-income countries. However, the
      prevalence of stroke survivors requiring help with at least 1 activity of daily
      living is already at high-income country levels. South Africa suffers from a huge
      burden of HIV/AIDS and diseases of poverty and violence and now faces the
      challenge of adapting its health systems to face the coming epidemic of vascular
      disease.

PMID- 14963281
TI  - Serial urinary 11-dehydrothromboxane B2, aspirin dose, and vascular events in
      blacks after recent cerebral infarction.
AB  - BACKGROUND AND PURPOSE: Incomplete platelet inhibition by aspirin (aspirin
      resistance) may be a reason for stroke recurrence in some patients. 11
      dehydrothromboxane B2 (11-DTB2) is a stable thromboxane A2 metabolite that
      reflects in vivo platelet activation. This pilot study was intended to evaluate
      the reproducibility of urinary 11-DTB2 over time and to look for evidence of
      aspirin resistance. METHODS: All subjects were screened for the African American
      Antiplatelet Stroke Prevention Study (AAASPS) 7 to 90 days after noncardioembolic
      cerebral infarction. Of 83 subjects with at least 1 urine sample, 52 were
      enrolled in AAASPS (randomized to blinded treatment with aspirin 650 mg/d or
      ticlopidine 500 mg/d), and 31 were enrolled in an open-label antiplatelet therapy
      cohort. Subjects were followed up for 2 years, with 11-DTB2 measurements
      scheduled at baseline and 6, 12, and 24 months. Vascular events were cerebral
      infarction, myocardial infarction, or vascular death. RESULTS: Despite
      considerable individual up or down fluctuations, the median 11-DTB2 change did
      not significantly differ from zero in any of the subgroups. However, in 6
      subjects with a 4-fold decrease in aspirin dose from 1300 to 325 or 81 mg/d, the
      11-DTB2 level increased from 611 to 1881 pg/mg creatinine (P=0.06). Vascular
      events occurred in 7 of 61 aspirin-treated subjects, and 11-DTB2 levels did not
      correlate with the events. CONCLUSIONS: Fluctuations in urinary 11-DTB2 after
      cerebral infarction in blacks do not correlate with changes in aspirin doses,
      except perhaps when the dose changes by a factor of 4 or more. A larger study is
      needed to look further for aspirin resistance.

PMID- 14963283
TI  - Absence of association between polymorphisms in the hemostatic factor pathway
      genes and carotid intimal medial thickness: the Framingham Heart Study.
AB  - BACKGROUND AND PURPOSE: Fibrinogen, plasminogen activator inhibitor-1, and other
      key proteins in the coagulation cascade have been implicated in the origin of
      cardiovascular disease. Polymorphisms in genes encoding these proteins have been
      associated with variability in plasma levels of these proteins. Carotid intimal
      medial thickness (IMT) is a heritable, quantitative measure of atherosclerosis
      that is predictive of subsequent myocardial infarction and stroke. We sought to
      test whether carotid IMT is associated with polymorphisms in several well
      characterized genes in the hemostatic factor pathways. METHODS: Here, 867 men and
      911 women (mean age, 57 years) in the Framingham offspring cohort underwent B
      mode carotid ultrasonography to determine the mean internal (ICA) and common
      carotid artery (CCA) IMT. Age-, sex-, and multivariable-adjusted linear
      regression was used to estimate the association of the following variants with
      log-transformed CCA and ICA IMT: factor V Leiden, factor VII Arg/Gln, fibrinogen
      HindIII beta-148, plasminogen activator inhibitor-1 4G/5G, and the glycoprotein
      IIIa Pl(A2) polymorphism. RESULTS: Mean ICA IMT was 0.58 mm; mean CCA IMT was
      0.60 mm. There were no differences in ICA or CCA IMT by genotype for any of the
      candidate genes in unadjusted, age- or sex-adjusted, and multivariable-adjusted
      models. CONCLUSIONS: There is no evidence for an association between well-studied
      polymorphisms in the hemostatic factor genes and carotid IMT. Whether other
      common genetic variants in hemostatic factor genes are associated with
      subclinical atherosclerosis remains to be determined.

PMID- 14963284
TI  - Electrocardiographic abnormalities and serum magnesium in patients with
      subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: ECG abnormalities and hypomagnesemia frequently occur
      after aneurysmal subarachnoid hemorrhage (SAH). Because hypomagnesemia is
      associated with several ECG abnormalities, we studied whether hypomagnesemia
      mediates ECG abnormalities after SAH. METHODS: We prospectively studied a
      consecutive series of 62 patients admitted within 72 hours after aneurysmal SAH.
      A standard 12-lead ECG and serum magnesium measurement were routinely performed
      at admission. The relationship between serum magnesium and ECG abnormalities was
      assessed with linear regression analysis and the Mann-Whitney test in case of
      dichotomized ECG abnormalities. RESULTS: Hypomagnesemia was present in 23
      patients (37%), and 38 patients (61%) had a long QTc duration. Low serum
      magnesium was related to a long PR interval (P=0.001) and a shorter QTc interval
      (P=0.004). Adjustment for World Federation of Neurological Surgeons score,
      hydrocephalus, and the amount of cisternal and ventricular blood did not
      influence these relations. CONCLUSIONS: In patients with SAH, lower serum
      magnesium levels are related to less pronounced increase in the QTc interval.
      Although the direction of the relation was unexpected, decreased serum magnesium
      might be the missing link between SAH and ECG abnormalities.

PMID- 14963285
TI  - Noninvasive phenotypes of atherosclerosis: similar windows but different views.
AB  - BACKGROUND AND PURPOSE: Noninvasive measures of atherosclerosis, such as carotid
      intima-media thickness, total carotid plaque area, and carotid stenosis, probably
      represent different phenotypes with distinct determinants. For instance, total
      carotid plaque area may reflect atherosclerotic lesion size more closely than
      carotid stenosis, which instead may reflect hemodynamic compromise within the
      arterial lumen. METHODS: In 1821 patients from a Premature Atherosclerosis
      Clinic, we studied determinants of total carotid plaque area and carotid stenosis
      as measured by ultrasound using multivariate regression analysis with traditional
      risk factors and some emerging risk factors. RESULTS: Regression modeling showed
      that (1) traditional atherosclerosis risk factors were more strongly associated
      with total carotid plaque area than with carotid stenosis (R=0.53 and 0.13,
      respectively), and (2) individual risk factors had different relationships with
      total carotid plaque area and carotid stenosis. For instance, age accounted for
      53% and 26% of the explained variance of total carotid plaque area and carotid
      stenosis, respectively. Female sex was inversely associated with total carotid
      plaque area but positively associated with carotid stenosis. Nontraditional risk
      variables such as plasma homocysteine had different associations with the 2
      analytes. CONCLUSIONS: Total carotid plaque area and carotid stenosis had
      different associations with specific atherosclerosis risk factors. Thus, for
      future studies of the determinants of atherosclerosis, it is important to
      distinguish between different phenotypes and to appreciate that they will not
      necessarily have the same determinants.

PMID- 14963286
TI  - Comparison of transcranial brain tissue perfusion images between ultraharmonic,
      second harmonic, and power harmonic imaging.
AB  - BACKGROUND AND PURPOSE: To clarify optimal brain tissue perfusion images
      visualized by transcranial ultrasound harmonic imaging, we compared gray-scale
      integrated backscatter (IBS) images of new ultraharmonic imaging (UHI) and
      conventional second harmonic imaging (SHI) with power harmonic imaging (PHI)
      (harmonic B-mode with harmonic power Doppler images) in 10 patients with and 4
      without a temporal skull. METHODS: Using a SONOS 5500 (Philips), we evaluated
      transient response images taken after a bolus Levovist injection at a horizontal
      diencephalic plane via temporal windows. Based on transmitting/receiving
      frequencies (MHz), 4 imaging procedures using an S3 transducer (SHI2.6 [1.3/2.6],
      UHI [1.3/3.6], PHI2.6 [1.3/2.6], and PHI3.2 [1.6/3.2]) and 2 imaging procedures
      using an S4 transducer (SHI3.6 [1.8/3.6] and PHI3.6 [1.8/3.6]) were compared in
      terms of size and location, peak intensity (PI), contrast area demarcation, and
      background image quality. RESULTS: In intact skull cases, gray-scale imaging
      tended to show larger contrast areas than PHI. A large contrast area was most
      frequently observed in SHI2.6 images, despite there being more high-PI cases in
      UHI. No contrast area with unclear background was observed in a few cases. In
      craniectomized cases, all contrast images tended to have large and high PI
      compared with the intact skull cases. PHI, particularly PHI3.6, demonstrated
      sharper demarcation and a clearer background than gray-scale imaging.
      CONCLUSIONS: Transcranial gray-scale SHI using a low receiving frequency of 2.6
      MHz is the superior method. PHI identifies contrast area localization better than
      gray-scale imaging and is particularly suitable for intraoperative and
      postoperative cases.

PMID- 14963287
TI  - Cerebral ischemia in aneurysmal subarachnoid hemorrhage: a correlative
      microdialysis-PET study.
AB  - BACKGROUND AND PURPOSE: Cerebral microdialysis (MD) is discussed as a technique
      for detection of cerebral ischemia in subarachnoid hemorrhage; however, clinical
      data on cerebral blood flow (CBF) are limited in these patients. The main
      objective of this study was to investigate whether pathological MD parameters
      reflect a reduced regional CBF (rCBF) determined by 15O-H2O PET. METHODS:
      Thirteen subarachnoid hemorrhage patients (age, 48.7+/-15.0 years; World
      Federation of Neurological Surgeons grade 1 to 5) were studied. Extracellular
      glucose, lactate, lactate/pyruvate (L/P) ratio, glutamate, and glycerol levels
      were analyzed hourly. rCBF was determined in the volume of interest of the MD
      catheter and all vascular territories. MD values were correlated to rCBF on the
      day of PET. Then, MD concentrations of asymptomatic versus ischemic phases (3-day
      medians) were analyzed. RESULTS: In symptomatic patients (n=10), rCBF was
      significantly lower compared with controls (n=3, P=0.048). Glutamate correlated
      best with rCBF (r=-0.66; P=0.014), followed by glycerol (r=-0.62; P=0.021). The
      L/P ratio was most sensitive (0.82) and specific (1.0) in indicating symptoms of
      ischemia, but only during longer periods of ischemia. CONCLUSIONS: rCBF
      correlates best with glutamate, followed by glycerol, whereas the L/P ratio is
      sensitive only after longer periods of ischemia. Clinically relevant regional
      metabolic derangements occur already above an rCBF of 20 mL x 100 g(-1).min(-1).
      Future research should focus on identifying alternative causes of metabolic
      derangement in subarachnoid hemorrhage patients and optimal treatment management
      in these patients.

PMID- 14963288
TI  - Transient ischemic attacks before ischemic stroke: preconditioning the human
      brain? A multicenter magnetic resonance imaging study.
AB  - BACKGROUND AND PURPOSE: We investigated whether transient ischemic attacks (TIAs)
      before stroke can induce tolerance by raising the threshold of tissue
      vulnerability in the human brain. METHODS: Sixty-five patients with first-ever
      ischemic territorial stroke received diffusion- and perfusion-weighted MRI within
      12 hours of symptom onset. Epidemiological and clinical data, lesion volumes in
      T2, apparent diffusion coefficient (ADC) maps and perfusion maps, and cerebral
      blood flow and cerebral blood volume values were compared between patients with
      and without a prodromal TIA. RESULTS: Despite similar size and severity of the
      perfusion deficit, initial diffusion lesions tended to be smaller and final
      infarct volumes were significantly reduced (final T2: 9.1 [interquartile range,
      19.7] versus 36.5 [91.2] mL; P=0.014) in patients with a history of TIA (n=16).
      This was associated with milder clinical deficits. CONCLUSIONS: The beneficial
      effect of TIAs on lesion size in ADC and T2 suggests the existence of endogenous
      neuroprotection in the human brain.

PMID- 14963289
TI  - MMP-9 polymorphisms are not associated with spontaneous cervical artery
      dissection.
AB  - BACKGROUND AND PURPOSE: Cervical artery dissection (CAD) is a common cause of
      ischemic stroke in young adults. Alteration in the structure of the vascular
      extracellular matrix has been described in CAD. Matrix metalloproteinases (MMPs)
      degrade extracellular matrix proteins and can lead to vascular damage. METHODS:
      We tested 2 different MMP-9 DNA polymorphisms, a CA repeat and a cytosine to
      thymidine transition in the promotor sequence, for frequency in 52 patients with
      CAD. We compared the results with those of 52 healthy controls. RESULTS: No
      differences were found in the allelic distribution of either polymorphism.
      CONCLUSIONS: Alleles of these well-characterized functional polymorphisms of MMP
      9 gene are not associated with structural alterations in the matrix of vessels of
      patients with CAD.

PMID- 14963290
TI  - Carotid arterial remodeling: a maladaptive phenomenon in type 2 diabetes but not
      in impaired glucose metabolism: the Hoorn study.
AB  - BACKGROUND AND PURPOSE: Deteriorating glucose tolerance is associated with an
      increased cardiovascular disease (CVD) risk. The underlying mechanisms remain
      unclear. Arterial remodeling is the change in structural properties through time
      in response to atherogenic and/or hemodynamic alterations and aims to maintain
      circumferential wall stress constant (sigma(C)). Arterial remodeling has not been
      studied in relation to glucose tolerance. METHODS: The study population consisted
      of 278 people with normal glucose metabolism, 168 with impaired glucose
      metabolism, and 301 with type 2 diabetes (DM-2); their mean age was 67.8 years.
      We assessed carotid intima-media thickness (IMT), interadventitial diameter
      (IAD), lumen diameter (LD), and sigma(C). RESULTS: After adjustment for age, sex,
      height, body mass index, and prior CVD, DM-2 was associated with increased IAD,
      IMT, and sigma(C) but not LD (regression coefficients: 0.24 mm; 95% confidence
      interval [CI], 0.07 to 0.41; 0.050 mm; 95% CI, 0.024 to 0.077; 5.00 kPa; 95% CI,
      0.92 to 9.08; and 0.13 mm; 95% CI, -0.03 to 0.29, respectively). After additional
      adjustment for pulse pressure, the association between DM-2 and IAD disappeared,
      whereas the association with IMT remained. After adjustment, impaired glucose
      metabolism was not significantly associated with LD (0.12 mm; 95% CI, -0.06 to
      0.33), sigma(C) (0.25 kPa; 95% CI, -4.49 to 4.98), IAD (0.08 mm; 95% CI, -0.11 to
      0.27), or IMT (0.029 mm; 95% CI, -0.002 to 0.060). However, the IMT regression
      coefficient was half that of DM-2. CONCLUSIONS: DM-2 is associated with preserved
      LD at increased IMT, which, however, does not normalize the increased sigma(C).
      In contrast, impaired glucose metabolism is not associated with changes in LD or
      IAD, whereas IMT is moderately increased but sigma(C) remains constant. Carotid
      remodeling in DM-2 thus appears maladaptive, which may explain the increased CVD
      risk, especially stroke, in DM-2.

PMID- 14963291
TI  - Science for all nations.

PMID- 14963292
TI  - Biomedical funding. A bumpy landing for cancer research.

PMID- 14963294
TI  - Space-based astronomy. Hubble's supporters attack NASA plan.

PMID- 14963293
TI  - Human cloning. Scientists take step toward therapeutic cloning.

PMID- 14963295
TI  - ITER. Compromise deal hinges on a graceful runner-up.

PMID- 14963296
TI  - Heart disease. Gene suggests asthma drugs may ease cardiovascular inflammation.

PMID- 14963297
TI  - Science funding. Hungarian science on the chopping block.

PMID- 14963298
TI  - Renewable energy. Hydrogen from ethanol goes portable.

PMID- 14963299
TI  - Kennewick Man. Scientists hope ruling will lead them to bones.

PMID- 14963301
TI  - Energy. Gas hydrate resource: smaller but sooner.

PMID- 14963300
TI  - Medicine. Caution urged on SARS vaccines.

PMID- 14963302
TI  - France. The winter of discontent.

PMID- 14963303
TI  - France. New faces, old promises.

PMID- 14963304
TI  - Society for Integrative and Comparative Biology meeting. Shark flexes its teeth
      for tough meals.

PMID- 14963305
TI  - Society for Integrative and Comparative Biology meeting. Estrogen may disrupt
      nitrogen fixation.

PMID- 14963306
TI  - Society for Integrative and Comparative Biology meeting. Bird in bush aids snake
      in grass.

PMID- 14963307
TI  - Society for Integrative and Comparative Biology meeting. Neural beginnings for
      the turtle's shell.

PMID- 14963308
TI  - Thailand's Prime-Boost HIV Vaccine Phase III.

PMID- 14963309
TI  - French scientists take a stand.

PMID- 14963310
TI  - How much at risk are cone snails?

PMID- 14963312
TI  - Comment on "Parasite selection for immunogenetic optimality".

PMID- 14963313
TI  - Policy rebuttal. HIV vaccine trial justified.

PMID- 14963314
TI  - Atmospheric science. Wind data: a promise in peril.

PMID- 14963315
TI  - Evolution. Transitions from nonliving to living matter.

PMID- 14963316
TI  - Plant sciences. A CONSTANS experience brought to light.

PMID- 14963317
TI  - Development. Making sense of the sensory lineage.

PMID- 14963318
TI  - PHYSICS. Packing in the spheres.

PMID- 14963319
TI  - Neuroscience. Conflict and cognitive control.

PMID- 14963320
TI  - Evolutionary ecology of the prezygotic stage.
AB  - The life cycles of sexually reproducing animals and flowering plants begin with
      male and female gametes and their fusion to form a zygote. Selection at this
      earliest stage is crucial for offspring quality and raises similar evolutionary
      issues, yet zoology and botany use dissimilar approaches. There are striking
      parallels in the role of prezygotic competition for sexual selection on males,
      cryptic female choice, sexual conflict, and against selfish genetic elements and
      genetic incompatibility. In both groups, understanding the evolution of sex
      specific and reproductive traits will require an appreciation of the effects of
      prezygotic competition on fitness.

PMID- 14963321
TI  - Evolution of a protochordate allorecognition locus.

PMID- 14963322
TI  - Structural basis of transcription: an RNA polymerase II-TFIIB cocrystal at 4.5
      Angstroms.
AB  - The structure of the general transcription factor IIB (TFIIB) in a complex with
      RNA polymerase II reveals three features crucial for transcription initiation: an
      N-terminal zinc ribbon domain of TFIIB that contacts the "dock" domain of the
      polymerase, near the path of RNA exit from a transcribing enzyme; a "finger"
      domain of TFIIB that is inserted into the polymerase active center; and a C
      terminal domain, whose interaction with both the polymerase and with a TATA box
      binding protein (TBP)-promoter DNA complex orients the DNA for unwinding and
      transcription. TFIIB stabilizes an early initiation complex, containing an
      incomplete RNA-DNA hybrid region. It may interact with the template strand, which
      sets the location of the transcription start site, and may interfere with RNA
      exit, which leads to abortive initiation or promoter escape. The trajectory of
      promoter DNA determined by the C-terminal domain of TFIIB traverses sites of
      interaction with TFIIE, TFIIF, and TFIIH, serving to define their roles in the
      transcription initiation process.

PMID- 14963323
TI  - Ultra-low thermal conductivity in W/Al2O3 nanolaminates.
AB  - Atomic layer deposition and magnetron sputter deposition were used to synthesize
      thin-film multilayers of W/Al(2)O(3). With individual layers only a few
      nanometers thick, the high interface density produced a strong impediment to heat
      transfer, giving rise to a thermal conductivity of approximately 0.6 watts per
      meter per kelvin. This result suggests that high densities of interfaces between
      dissimilar materials may provide a route for the production of thermal barriers
      with ultra-low thermal conductivity.

PMID- 14963324
TI  - Improving the density of jammed disordered packings using ellipsoids.
AB  - Packing problems, such as how densely objects can fill a volume, are among the
      most ancient and persistent problems in mathematics and science. For equal
      spheres, it has only recently been proved that the face-centered cubic lattice
      has the highest possible packing fraction phi=pi/18 approximately 0.74. It is
      also well known that certain random (amorphous) jammed packings have phi
      approximately 0.64. Here, we show experimentally and with a new simulation
      algorithm that ellipsoids can randomly pack more densely-up to phi= 0.68 to 0.71
      for spheroids with an aspect ratio close to that of M&M's Candies-and even
      approach phi approximately 0.74 for ellipsoids with other aspect ratios. We
      suggest that the higher density is directly related to the higher number of
      degrees of freedom per particle and thus the larger number of particle contacts
      required to mechanically stabilize the packing. We measured the number of
      contacts per particle Z approximately 10 for our spheroids, as compared to Z
      approximately 6 for spheres. Our results have implications for a broad range of
      scientific disciplines, including the properties of granular media and ceramics,
      glass formation, and discrete geometry.

PMID- 14963325
TI  - Renewable hydrogen from ethanol by autothermal reforming.
AB  - Ethanol and ethanol-water mixtures were converted directly into H2 with
      approximately 100% selectivity and >95% conversion by catalytic partial
      oxidation, with a residence time on rhodium-ceria catalysts of <10 milliseconds.
      Rapid vaporization and mixing with air with an automotive fuel injector were
      performed at temperatures sufficiently low and times sufficiently fast that
      homogeneous reactions producing carbon, acetaldehyde, ethylene, and total
      combustion products can be minimized. This process has great potential for low
      cost H2 generation in fuel cells for small portable applications where liquid
      fuel storage is essential and where systems must be small, simple, and robust.

PMID- 14963326
TI  - Chondrules with peculiar REE patterns: implications for solar nebular
      condensation at high C/O.
AB  - Rare earth element (REE) data from two ordinary chondrite chondrules show
      distinct negative chondrite-normalized concentration anomalies of samarium,
      europium, and ytterbium. The peculiar patterns may be the result of REE gas/solid
      fractionation at an oxygen fugacity lower than has been assumed for the canonical
      solar nebula. We suggest that the two ordinary chondrite chondrules acquired the
      fractionated REE patterns by incorporation of highly reduced, ultrarefractory
      condensates in their precursors. This interpretation implies that high
      temperature condensation processes occurred in nebular environments with a strong
      deficit in oxygen, such as regions with an enhanced carbon/oxygen ratio.

PMID- 14963327
TI  - Lowland forest loss in protected areas of Indonesian Borneo.
AB  - The ecology of Bornean rainforests is driven by El Nino-induced droughts that
      trigger synchronous fruiting among trees and bursts of faunal reproduction that
      sustain vertebrate populations. However, many of these species- and carbon-rich
      ecosystems have been destroyed by logging and conversion, which increasingly
      threaten protected areas. Our satellite, Geographic Information System, and field
      based analyses show that from 1985 to 2001, Kalimantan's protected lowland
      forests declined by more than 56% (>29,000 square kilometers). Even uninhabited
      frontier parks are logged to supply international markets. "Protected" forests
      have become increasingly isolated and deforested and their buffer zones degraded.
      Preserving the ecological integrity of Kalimantan's rainforests requires
      immediate transnational management.

PMID- 14963328
TI  - Photoreceptor regulation of CONSTANS protein in photoperiodic flowering.
AB  - Many plants flower in response to seasonal fluctuations in day length. The
      CONSTANS (CO) gene of Arabidopsis promotes flowering in long days. Flowering is
      induced when CO messenger RNA expression coincides with the exposure of plants to
      light. However, how this promotes CO activity is unknown. We show that light
      stabilizes nuclear CO protein in the evening, whereas in the morning or in
      darkness the protein is degraded by the proteasome. Photoreceptors regulate CO
      stability and act antagonistically to generate daily rhythms in CO abundance.
      This layer of regulation refines the circadian rhythm in CO messenger RNA and is
      central to the mechanism by which day length controls flowering.

PMID- 14963329
TI  - Nanotubular highways for intercellular organelle transport.
AB  - Cell-to-cell communication is a crucial prerequisite for the development and
      maintenance of multicellular organisms. To date, diverse mechanisms of
      intercellular exchange of information have been documented, including chemical
      synapses, gap junctions, and plasmodesmata. Here, we describe highly sensitive
      nanotubular structures formed de novo between cells that create complex networks.
      These structures facilitate the selective transfer of membrane vesicles and
      organelles but seem to impede the flow of small molecules. Accordingly, we
      propose a novel biological principle of cell-to-cell interaction based on
      membrane continuity and intercellular transfer of organelles.

PMID- 14963330
TI  - Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization
      and apoptosis.
AB  - The tumor suppressor p53 exerts its anti-neoplastic activity primarily through
      the induction of apoptosis. We found that cytosolic localization of endogenous
      wild-type or trans-activation-deficient p53 was necessary and sufficient for
      apoptosis. p53 directly activated the proapoptotic Bcl-2 protein Bax in the
      absence of other proteins to permeabilize mitochondria and engage the apoptotic
      program. p53 also released both proapoptotic multidomain proteins and BH3-only
      proteins [Proapoptotic Bcl-2 family proteins that share only the third Bcl-2
      homology domain (BH3)] that were sequestered by Bcl-xL. The transcription
      independent activation of Bax by p53 occurred with similar kinetics and
      concentrations to those produced by activated Bid. We propose that when p53
      accumulates in the cytosol, it can function analogously to the BH3-only subset of
      proapoptotic Bcl-2 proteins to activate Bax and trigger apoptosis.

PMID- 14963331
TI  - Structural basis of transcription: separation of RNA from DNA by RNA polymerase
      II.
AB  - The structure of an RNA polymerase II-transcribing complex has been determined in
      the posttranslocation state, with a vacancy at the growing end of the RNA-DNA
      hybrid helix. At the opposite end of the hybrid helix, the RNA separates from the
      template DNA. This separation of nucleic acid strands is brought about by
      interaction with a set of proteins loops in a strand/loop network. Formation of
      the network must occur in the transition from abortive initiation to promoter
      escape.

PMID- 14963332
TI  - Modulation of Th1 activation and inflammation by the NF-kappaB repressor Foxj1.
AB  - Forkhead transcription factors play key roles in the regulation of immune
      responses. Here, we identify a role for one member of this family, Foxj1, in the
      regulation of T cell activation and autoreactivity. Foxj1 deficiency resulted in
      multiorgan systemic inflammation, exaggerated Th1 cytokine production, and T cell
      proliferation in autologous mixed lymphocyte reactions. Foxj1 suppressed NF
      kappaB transcription activity in vitro, and Foxj1-deficient T cells possessed
      increased NF-kappaB activity in vivo, correlating with the ability of Foxj1 to
      regulate IkappaB proteins, particularly IkappaBbeta. Thus, Foxj1 likely modulates
      inflammatory reactions and prevents autoimmunity by antagonizing proinflammatory
      transcriptional activities. These results suggest a potentially general role for
      forkhead genes in the enforcement of lymphocyte quiescence.

PMID- 14963333
TI  - Anterior cingulate conflict monitoring and adjustments in control.
AB  - Conflict monitoring by the anterior cingulate cortex (ACC) has been posited to
      signal a need for greater cognitive control, producing neural and behavioral
      adjustments. However, the very occurrence of behavioral adjustments after
      conflict has been questioned, along with suggestions that there is no direct
      evidence of ACC conflict-related activity predicting subsequent neural or
      behavioral adjustments in control. Using the Stroop color-naming task and
      controlling for repetition effects, we demonstrate that ACC conflict-related
      activity predicts both greater prefrontal cortex activity and adjustments in
      behavior, supporting a role of ACC conflict monitoring in the engagement of
      cognitive control.

PMID- 14963334
TI  - Medicago truncatula DMI1 required for bacterial and fungal symbioses in legumes.
AB  - Legumes form symbiotic associations with both mycorrhizal fungi and nitrogen
      fixing soil bacteria called rhizobia. Several of the plant genes required for
      transduction of rhizobial signals, the Nod factors, are also necessary for
      mycorrhizal symbiosis. Here, we describe the cloning and characterization of one
      such gene from the legume Medicago truncatula. The DMI1 (does not make
      infections) gene encodes a novel protein with low global similarity to a ligand
      gated cation channel domain of archaea. The protein is highly conserved in
      angiosperms and ancestral to land plants. We suggest that DMI1 represents an
      ancient plant-specific innovation, potentially enabling mycorrhizal associations.

PMID- 14963335
TI  - A putative Ca2+ and calmodulin-dependent protein kinase required for bacterial
      and fungal symbioses.
AB  - Legumes can enter into symbiotic relationships with both nitrogen-fixing bacteria
      (rhizobia) and mycorrhizal fungi. Nodulation by rhizobia results from a signal
      transduction pathway induced in legume roots by rhizobial Nod factors. DMI3, a
      Medicago truncatula gene that acts immediately downstream of calcium spiking in
      this signaling pathway and is required for both nodulation and mycorrhizal
      infection, has high sequence similarity to genes encoding calcium and calmodulin
      dependent protein kinases (CCaMKs). This indicates that calcium spiking is likely
      an essential component of the signaling cascade leading to nodule development and
      mycorrhizal infection, and sheds light on the biological role of plant CCaMKs.

PMID- 14963336
TI  - Local ordering in the pseudogap state of the high-Tc superconductor
      Bi2Sr2CaCu2O(8+delta).
AB  - We report atomic-scale characterization of the pseudogap state in a high-Tc
      superconductor, Bi2Sr2CaCu2O(8+delta). The electronic states at low energies
      within the pseudogap exhibit spatial modulations having an energy-independent
      incommensurate periodicity. These patterns, which are oriented along the copper
      oxygen bond directions, appear to be a consequence of an electronic ordering
      phenomenon, the observation of which correlates with the pseudogap in the density
      of electronic states. Our results provide a stringent test for various ordering
      scenarios in the cuprates, which have been central in the debate on the nature of
      the pseudogap and the complex electronic phase diagram of these compounds.

PMID- 14963337
TI  - Evidence of a pluripotent human embryonic stem cell line derived from a cloned
      blastocyst.
AB  - Somatic cell nuclear transfer (SCNT) technology has recently been used to
      generate animals with a common genetic composition. In this study, we report the
      derivation of a pluripotent embryonic stem (ES) cell line (SCNT-hES-1) from a
      cloned human blastocyst. The SCNT-hES-1 cells displayed typical ES cell
      morphology and cell surface markers and were capable of differentiating into
      embryoid bodies in vitro and of forming teratomas in vivo containing cell
      derivatives from all three embryonic germ layers in severe combined
      immunodeficient mice. After continuous proliferation for more than 70 passages,
      SCNT-hES-1 cells maintained normal karyotypes and were genetically identical to
      the somatic nuclear donor cells. Although we cannot completely exclude the
      possibility that the cells had a parthenogenetic origin, imprinting analyses
      support a SCNT origin of the derived human ES cells.

PMID- 14963338
TI  - [New trends in child cancer information systems development in Poland].
AB  - On the basis of previously performed system analysis, the structure, organisation
      and technological platform of children cancer information system in Poland is
      proposed. The postulated system should preserve the division into the national
      children's cancer register dedicated to epidemiological analyses and clinical
      information systems for deepened clinical analyses. The project anticipates
      evolutional development taking into account global norms and standards as well as
      modern telematic technology.

PMID- 14963339
TI  - [Children's cancer registration in Poland].
AB  - Yearly, 1300-1400 children fall ill with cancer in Poland. New child cancer cases
      are registered by two independent registration systems: general National Cancer
      Register (NCR) in Warsaw and one established in Lublin, concerning only children
      0-17 years old. The NCR existing for 50 years, gathers epidemiological data and
      is functioning very well. Nevertheless, some updates concerning technological
      platform, norms and standards could be postulated. The Lublin Children's Register
      has been established only a few years ago. It gathers extended clinical data,
      unfortunately not fully formalized, but using ICD-O classification. Modern
      children's cancer register in Poland should evolve from both existing
      registration systems fulfilling expectations of epidemiologists and physicians.

PMID- 14963340
TI  - [Incidence of childhood solid tumours in Lublin region from 1988 to 2000].
AB  - The purpose of this study was the analysis of number and structure of new solid
      tumours and tumour morbidity among children 0-17 years old, in the Lublin Region
      of Poland, from 1988 to 2000. The analysis was based on sex, age and place of
      domicile (urban/rural region). During this time in the Lublin Region 344 cases of
      childhood solid tumours were reported; it was 36.4% of all childhood cancers
      diagnosed in this region. The structure of the disease was related to sex, age
      and the place of living. The mean morbidity rate was 42.2 per 1 mln (among boys -
      42.2, girls - 42.4). The highest incidence rate was observed among children 0-4
      years old (78.1 per 1 million). Higher morbidity was noted among patients living
      in urban regions (47.3 vs 37.6 / million).

PMID- 14963341
TI  - [Chromosomal aberrations in differential diagnosis and prognosis in childhood
      acute leukaemias].
AB  - The purpose of our study was to determine the frequency of specific, somatic
      chromosomal abnormalities in children with acute leukaemia and to evaluate the
      usefulness of cytogenetic study and DNA analysis as diagnostic and prognostic
      tools in these diseases. Among 63 children with acute lymphoblastic leukaemia
      (ALL) and 13 with de novo acute myeloblastic leukaemia (AML), hyperdiploidy was
      found in 25% and hypodiploidy in 6% of patients. Normal karyotype was found in
      44% whereas pseudodiploidy in 25% of children with ALL. In the group of children
      with AML, pseudodiploidy was found in 2 cases and normal karyotype in 11.
      Translocations t(12;21), t(4;11), t(6;11) and t(9;11) failed to be detected by
      conventional cytogenetics. They were found by molecular methods. On the other
      hand, the t(1;14) and t(8;14) translocations were detected exclusively by
      karyotype analysis. The probability of event-free survival (EFS) in the group of
      children with ALL and genetic abnormalities of favourable prognosis was 96%
      whereas in the group of children with unfavourable prognosis it was 55%.
      Classical cytogenetic methods together with more sensitive molecular tests allow
      to detect diagnostically and prognostically relevant chromosomal aberrations in
      childhood acute leukaemias.

PMID- 14963342
TI  - [Nephroblastoma in children aged less than 6 months at diagnosis].
AB  - We present the results of treatment of kidney tumours in newborns and infants
      aged less than 6 months, in the years 1993-2000, from the Nephroblastoma
      Committee of the Polish Paediatric Group of Solid Tumours (PPGGL). We have
      analysed the diagnostic and treatment results in the group of 31 children aged 0
      to 6 months. For 19 children registered between 1993 and 1996, event-free
      survival (EFS) and overall survival (AS) were assessed. Among 450 children
      registered between 1993 and 2000 by PPGGL and treated for kidney tumours, there
      were 31 (7.1%) newborns and infants aged below 6 months. The accuracy of
      diagnosis based on imaging studies was 97%. Only in one child the initial
      diagnosis of kidney tumour was not confirmed; cystic degeneration of kidney was
      finally established. The tumours removed during surgery were small, with average
      size 213 cm3, and in half of the cases the size of the tumour did not exceed 165
      cm3. Primary complete excision of the tumour was performed in 21 children
      (67.7%). In 10 cases histopathology confirmed mesoblastic nephroma, in 19 cases
      nephroblastoma and in 2 cases sarcoma clarocellulare. In 10 infants (32.2%) with
      nephroblastoma delayed surgery preceded by chemotherapy was performed.
      Indications for initial preoperative chemotherapy comprised: tumour in a single
      kidney, tumour in a horseshoe kidney, preoperative diagnostic biopsy of the
      tumour and large tumour in neonates older than 3 months. In almost 70% of the
      children the stage of advancement was low (stage I and IIN-). Histopathology of
      excised tumours confirmed in 42% of cases low risk, and in 51.6% intermediate
      risk. Intraoperative complications occurred in 5 infants (16%). The tolerance of
      reduced chemotherapy by the infants was good. AS was 100%. ESF for the 19
      children registered for nephroblastoma between 1993 and 1996 for all stages of
      advancement and types of histology was 94.75%. CONCLUSIONS: 1) Mesoblastic
      nephroma and low risk nephroblastoma are the most common tumours in children
      within the first three years of life. 2) The results of treatment of
      nephroblastoma in the youngest children (below 6 months of age) are the most
      favourable and represent world standards.3) Surgical complications in children
      operated primarily for nephroblastoma indicate the need of performing such
      operations in academic centres, specialised in newborn surgery. 4) In infants
      with extensive kidney tumours older than 3 months, primarily considered as
      inoperative, individual induction chemotherapy should be taken into account.

PMID- 14963343
TI  - [Renal function and size after complex treatment of Wilms' tumour].
AB  - The aim of our study was to measure renal function and growth in survivors of
      unilateral Wilms' tumour in 21 children and young adults (7 female). The mean age
      was 12.6 +/- 4.8 years, mean follow-up time was 7.01 +/- 4.25 years: seven of the
      group received irradiation (35 Gy). Blood pressure was normal in all patients.
      Three of them had elevated cystatin C and clearance of cystatin C below
      referenced normal value. The others had normal renal function tests (cystatin C,
      creatinine and cystatin clearance, B2 microglobulin, microalbuminuria,
      osmolality). Compared to the control we found higher cystatin C values in
      children treated before the age 3 years old (p=0.03) and in children treated more
      than 5 years before (p=0.03), and lower cystatin clearance in group treated
      before the age 3 years old (p=0,03). No difference between the irradiated and non
      irradiated group was found. We observed a greater increase in volume (155.9% +/-
      33.4) than in length (127.9% +/- 6.3). The highest rise of renal volume was in
      children treated more than 5 years before (174.6% +/- 22.3). In conclusion, our
      data suggest that after combined treatment for Wilms' tumour compensatory renal
      hypertrophy and a tendency progressive renal dysfunction takes place.

PMID- 14963344
TI  - [Bilateral Wilms' tumour. Results of treatment in 29 children].
AB  - Retrospective analysis of 29 children with bilateral Wilms' Tumour, 14 boys and
      15 girls, aged 4m-5 years, from regional centres of paediatric oncology in
      Poland, treated according to the O1-92 PPGL Protocol of Wilms' tumour, was
      performed. All patients were treated with two (ACT + VCR) or three (ACT, VCR,
      DOX) cytostatic drugs preoperatively, and 26 were operated upon after
      cytoreductive pretreatment. In 12 children nephrectomy was performed. In 28,
      kidney sparing surgery was possible and made with success. 2 patients who
      presented disseminated disease and 1 with nephroblastomatosis were given
      chemotherapy. 19 out of 29 (65.5%) are alive including 1 patient with
      nephroblastoma. EFS calculated according to Kaplan-Meier analysis for this group,
      was 58% at 67 months.

PMID- 14963345
TI  - [Psychosocial problems of well siblings of children with cancer].
AB  - Children with cancer are not the only victims of the effects of the chronic or
      terminal illness and its treatment. Siblings of childhood cancer patients
      experience significant psychosocial distress and are isolated from support
      systems inside and outside the family. Fortunately, the impact of cancer on the
      patient's family has increasingly become the focus of much research. This article
      summarizes the issues and problems unique to the healthy brothers and sisters of
      children with cancer. It characterizes the impact on family functioning,
      intrapersonal and interpersonal problems, academic performance and psychosomatic
      symptoms. There is necessary to elaborate and introduce into practice the
      recommendation of early psychological intervention for healthy sibling and
      parents as well. Recommendations are needed for integrating preventive
      intervention and guidelines for caregivers in helping these siblings and their
      parents.

PMID- 14963346
TI  - [Case of subtelomeric aberration as a cause of familial intellectual disability
      with congenital defects and dysmorphic features--problems of diagnosis and
      genetic counseling].
AB  - Intellectual disability, defined as an IQ less than 70, occurs in 2-3% of the
      population and is both a medical and social problem of outstanding importance.
      Establishing its aetiology is not always easy, but it is a necessary condition in
      providing genetic counseling for families. Until now, the aetiology of mental
      retardation remains unknown in about half of the cases. Chromosomal aberrations
      are found in about 30-40% of moderately and profoundly intellectually impaired.
      Submicroscopic chromosomal aberrations involving the telomeric regions of
      chromosomes discovered in the recent years, are responsible for 4-9% cases of
      idiopathic mental retardation. Identification of very small structural
      rearrangements in the telomeric regions of the chromosomes requires another
      strategy than those applied in routine classic methods of chromosomal analysis
      (fluorescence in situ hybridisation in situ FISH). We present several cases of
      mental retardation with congenital defects and dysmorphic features which occurred
      in one family. Submicroscopic aberration in the telomeric regions of chromosomes
      7 and 10 was revealed as a cause of mental retardation in this family. That
      aberration was a result of familial reciprocal translocation which had been not
      previously identified by routine cytogenetic methods. Detailed retrospective
      clinical characteristics of the proband and his affected relatives is presented.
      Variable clinical expression in presented cases in relation to difficulties in
      diagnosis and genetic counseling is discussed.

PMID- 14963347
TI  - Antiandrogen monotherapy: recommendations for the treatment of prostate cancer.
AB  - OBJECTIVE: The concept of antiandrogens as monotherapy for the treatment of
      prostate cancer is discussed. METHODS: Both Medline and Current Contents were
      used to identify studies on antiandrogen monotherapy in prostate cancer. We tried
      to analyze this database critically to establish whether or not there is evidence
      for using this monotherapy. RESULTS: In particular, bicalutamide in monotherapy
      has been compared with castration in large international trials. Results show
      that antiandrogen monotherapy is inferior to castration in patients with
      metastatic tumour but the difference in median survival is limited. In locally
      advanced M0 prostate cancer bicalutamide 150 mg monotherapy seems equivalent to
      castration in terms of overall survival and time to progression. Analysis of
      quality of life showed that there is evidence of some benefits from bicalutamide
      when compared to castration in both sexual interest and physical capacity.
      CONCLUSION: Antiandrogens in monotherapy can be effective and well tolerated.
      However, more research is needed because none of the available compounds have
      definitively been proven to be equivalent to castration.

PMID- 14963348
TI  - Second transurethral resection of superficial transitional cell carcinoma of the
      bladder: a must even for experienced urologists.
AB  - INTRODUCTION: As even experienced urologists have a high percentage of persisting
      carcinoma after transurethral bladder tumour resection (TUR-B) the importance of
      a routine second resection in the management of transitional cell carcinoma (TCC)
      of the bladder is defined. PATIENTS AND METHODS: The medical records of all
      patients treated with TUR-B at our institution between January 1989 and September
      2000 were reviewed. 214 patients with pTa and pT1 carcinoma undergoing a second
      resection 4-6 weeks later were included in the analysis. The rate of persisting
      carcinoma in the second resection was compared to the actual tumour stage and
      grade, the patient's age, sex and the experience of the urologist performing the
      resection. RESULTS: Of the 214 patients 99 had pTa and 115 pT1 carcinoma. The
      rate of persisting tumour in the second resection was 27% in pTa and 37% in pT1
      carcinoma. This rate was independent of the patient's age and sex. Urologists in
      training had an equally low rate of persisting carcinoma in the second resection
      compared to senior urologists (p = 0.08). CONCLUSIONS: Routine second resection
      of superficial transitional cell carcinoma of the bladder should be part of the
      treatment even in larger operative experience.

PMID- 14963349
TI  - Survival rates after radical cystectomy according to tumor stage of bladder
      carcinoma at first presentation.
AB  - INTRODUCTION: The aim of this study was to establish to what extent the survival
      rates of muscle-invasive bladder carcinoma are influenced by the tumor stage at
      initial presentation. PATIENTS AND METHODS: This study examined the clinical
      course of 230 patients who underwent radical cystectomy for bladder carcinoma
      from 1992 to 2002. The patients were divided into three groups according to the
      histological results of the initial and final transurethral tumor resection
      (TURB). In group 1 (n = 41) radical cystectomy was carried out for a superficial
      bladder carcinoma which had a high likelihood of progressing. Group 2 (n = 57)
      consisted of patients who displayed a superficial tumor stage when they first
      presented and developed progressive muscle-invasive bladder carcinoma under
      conservative treatment. Group 3 (n = 132) was made up of patients who were
      already at the muscle-invasive tumor stage in the course of primary TURB. The
      histopathological characteristics of all transurethral tumor resections and
      radical cystectomy were recorded. Progression-free survival and overall survival
      in the three groups were then compared. RESULTS: The average patient age when
      cystectomy was carried out was 63.9 (35-80) years and the average follow-up
      period was 38 months. An average of 2.3 (1-16) transurethral tumor resections
      were carried out before radical cystectomy (median = 1). Progression-free
      survival and overall survival of all 230 patients was 54 and 50%, respectively,
      after 5 years. The best result was a 74% progression-free 5-year survival rate
      with organ-confined lymph node-negative tumors (n = 106) which was statistically
      significant (p = 0.0004) compared to the progression-free 5-year survival rate of
      50% for non-organ-confined, lymph node-negative tumors (n = 64). Lymph node
      positive patients achieved a progression-free survival rate of 21% after 5 years
      regardless of the tumor infiltration. Patients in group 1 achieved a progression
      free 5-year survival rate of 77% and an overall survival rate of 63% after 5
      years. In group 2 patients achieved a progression-free survival rate of 51% after
      5 years and an overall survival rate of 50%. In the case of primary muscle
      invasion (group 3), progression-free survival and overall survival were 49 and
      46%, respectively, after 5 years. There was no significant difference between
      groups 2 and 3 with regard to their progression-free or overall survival rates (p
      > 0.35). However, both groups displayed a significantly poorer progression-free
      and overall survival rate compared with group 1 (p < 0.01). CONCLUSION: Our
      results show that superficial bladder carcinoma with tumor progress to muscle
      invasion does not have a better prognosis after radical cystectomy than initial
      muscle-invasive bladder carcinoma. Survival rates in this group can only be
      improved by singling out patients on the basis of risk factors at an earlier
      stage and carrying out a cystectomy.

PMID- 14963350
TI  - CA19-9 as a serum marker for poor prognosis in urothelial carcinoma.
AB  - INTRODUCTION: To evaluate the role of serum carbohydrate antigen 19-9 (CA19-9) in
      the prognosis and follow-up evaluation of patients with urothelial carcinoma, the
      authors studied the association of the serum level and positive rate with
      clinical features such as infiltration and metastasis in 164 patients admitted to
      the authors' department. PATIENTS AND METHODS: This study included 164 cases of
      patients with urohelial carcinoma. The absolute value of the serum CA19-9 level
      and its positive rate were tested. Simple variant analysis and logistic
      regression analysis were used for estimation of statistical significance. Kaplan
      Meier's test and Cox's proportional hazard model were used for analysis of
      survival. RESULTS: Significant differences in the serum CA19-9 levels were found
      with regard to the following parameters: the presence or absence of metastasis,
      clinical stage, depth of invasion, and degree of differentiation. The positive
      rate displayed a significant difference only for the presence or absence of
      metastasis. With regard to the presence of metastasis, serum CA19-9 was a
      significant risk factor along with depth of invasion in logistic regression
      analysis. Comparison of the survival rate indicated the prognosis to be
      significantly poor in the positive group and serum CA19-9 was regarded to be a
      prognostic risk factor in analysis via the regression model. CONCLUSIONS: Serum
      CA19-9 is thought to serve as a significant marker for advanced cancer and tumors
      with highly malignant potential and is useful for predicting prognosis of the
      disease.

PMID- 14963351
TI  - Examination of tumorigenesis of precursor lesions in bladder cancer by in situ
      hybridization.
AB  - Through examinations using fluorescence in situ hybridization (FISH) of
      chromosomes 1 and 9, we tried to obtain more information on dysplasia and
      carcinoma in situ (Cis) in relation to the oncogenesis of bladder cancer. 63
      paraffin sections (dysplasia grades I-III and Cis) were evaluated, and 8 negative
      sections functioned as a control group. For FISH, DNA samples of CEP 1 and 9
      (alpha satellites) were chosen. Gains (aneuploidy) or losses (monosomy) of
      chromosomal material were determined microscopically. Dysplasia grades I-III
      showed a 5-18% aberration in chromosome 1 aneuploidy and a 19-29% aberration in
      monosomy 9. Cis revealed 27% aneuploidy of chromosomes 1 and 9. Although at
      present dysplasia grade III and Cis of the bladder are viewed as
      histopathologically identical, we examined both molecular genetic differences in
      chromosome 9. As referred to in the literature we found the same genetic
      aberrations for dysplasias (grades I-III) and noninvasive papillary bladder
      tumors as well as for Cis and solid invasive bladder cancer.

PMID- 14963352
TI  - New cut-off point between T1 and T2 renal cell carcinoma - necessary for a better
      discriminatory power of the TNM classification.
AB  - PURPOSE: We evaluated the pathological features of tumor size, lymph node and
      distant metastases, cell type, growth pattern, infiltration pattern, histological
      grade, local invasion and venous involvement of organ-confined renal carcinomas.
      The aim of this study was the re-evaluation of the TNM classification and the
      tumor cut-off point between T1 and T2 for renal cell carcinomas from the 1987 to
      the 1997 versions. MATERIALS AND METHODS: (1) Patients with renal cell carcinoma
      who had been operated between October 1992 and August 2001 were evaluated. 437 of
      691 patients showed T1 and T2 tumors. These organ-confined tumors have been
      divided into five groups: group 1: tumor-size of 20 mm or less (n = 16), group 2:
      21-30 mm (n = 79); group 3: 31-40 mm (n = 83; group 4: 41-70 mm (n = 184), and
      group 5: more than 70 mm in diameter (only T2, n = 75). Follow-up ranged from 0
      to 100 months (average 28.63 months). (2) Of 15,347 autopsies performed in Jena
      between 1985 and 1996, 272 renal cell carcinomas were revealed. In 145 of these
      272 cases renal cell carcinomas were limited to the kidney. These 145 tumors were
      divided accordingly into 5 groups: group 1: 20 mm or less (n = 33), group 2: 21-
      30 mm (n = 31); group 3: 31-40 mm (n = 29); group 4: 41-70 mm (n = 42), and group
      5: T2 (n = 10). Clinicopathological criteria examined were lymph node and distant
      metastases, cell type, growth pattern, infiltration pattern, histological grade,
      local invasion and venous involvement. To identify the optimal cut-off point
      between T1 and T2 disease the chi2 test was used. RESULTS: (1) In the clinical
      series only 1.8% (n = 8) of all cases showed lymph node metastases. Distant
      metastases were shown in 57 cases (13.04%); within group 1: 0%, group 2: 7.59%,
      group 3: 1.20%, group 4: 15.76%, group 5: 28%. The tumor grading was
      statistically correlated with tumor size. (2) In the pathological series 94 of
      the evaluated 145 patients were downstaged from T2(1987) to T1(1997). Lymph node
      and distant metastases were well correlated with tumor size. Lymph node
      metastases were seen in 0, 12.9, 31, 29.3 and 40% (group 1 to group 5) and
      distant metastases in 12.1, 25.8, 41.4, 47.7 and 60%. There were no statistically
      significant differences between T2(1997) and T1(3-7 cm). The tumor grading was
      statistically correlated with tumor size (grade 1: in 66.7, 25.8, 17.2, 9.5 and
      0%). CONCLUSION: Our data suggest that the current cut-off diameter between T1
      and T2 renal cell carcinomas (7 cm) is too high. Lowering the cut-off level will
      result in better discriminatory power of the TNM classification. From our data,
      we conclude that the cut-off diameter should be lowered to 3.5 cm (p < 0.001).

PMID- 14963353
TI  - Impact of imaging and thrombus level in management of renal cell carcinoma
      extending to veins.
AB  - OBJECTIVES: To evaluate the role of newer imaging modalities in the diagnosis and
      evaluation of management according to extent of renal vein (RV) or inferior vena
      cava (IVC) thrombi in patients with renal cell carcinoma. MATERIAL AND METHODS:
      Fifty-nine patients with renal cell carcinoma and tumor thrombus extension into
      the RV or IVC were studied. Diagnosis was based on contrast-enhanced CT, magnetic
      resonance imaging or color-Doppler ultrasonography. Surgical treatment was
      contemplated in 42 suitable patients and complete resection could be done in all
      but 3 cases. RESULTS: There were 48 males and 11 females with mean age of 51.8
      years. Isolated RV involvement was seen in 27 cases whereas IVC extension was
      present in 32 cases. The thrombus extent was infrahepatic in 62.5% (20/32)
      patients with IVC extension. With the newer imaging modalities like contrast
      enhanced CT, color-Doppler ultrasound and/or magnetic resonance imaging, correct
      diagnosis of the extent of the thrombus was possible in 95% of the patients. The
      accuracy of color-Doppler ultrasound was same as magnetic resonance imaging in
      the evaluation of the extent of the thrombus. In the present series a median
      follow-up of 4 years revealed a high incidence of local and distant recurrences
      and decreased survival in patients presenting with advanced disease, who had
      venous wall invasion. CONCLUSIONS: The extent of RV or IVC thrombi can be
      accurately diagnosed with contrast-enhanced CT scan and in case of doubt color
      Doppler ultrasound is a good alternative to magnetic resonance imaging.
      Management can be planned according to the level of the tumor thrombus. Invasion
      of the venous wall was found to be a bad prognostic factor affecting survival.

PMID- 14963354
TI  - A simple mathematical approach to calculate blood loss in radical prostatectomy.
AB  - INTRODUCTION: The aim of this study was to apply a simple mathematical approach
      to calculate blood loss in 126 patients undergoing radical retropubic
      prostatectomy (RRP). MATERIALS AND METHODS: Perioperative red blood cell loss
      (RBCL) was estimated by adding the difference in circulating red blood cells from
      before to after surgery to the allogeneic red blood cells transfused in the same
      period. RESULTS: Mean preoperative hematocrit was 45 +/- 4% and mean
      perioperative RBCL was 574 +/- 297 ml, corresponding to a mean equivalent whole
      blood loss (WBL) of 1,479 +/- 831 ml. Twenty of 126 patients (15.9%) received 42
      units of allogeneic packed red blood cells (PRBC), for a mean of 2.1 +/- 1.2
      U/patient. The transfusion rate was higher in patients with a preoperative
      hematocrit of 40% or less (45 vs. 13%, p = 0.014). CONCLUSIONS: Anatomical RRP is
      still associated with appreciable operative blood loss. Owing to the high
      preoperative hematocrit values, the allogeneic blood transfusion rate is low and
      the transfusion requirement of the majority of patients is limited to about 2
      units of PRBC. Preoperative autologous blood augmentation strategies may not be
      routinely needed for patients with a basal hematocrit of >40%.

PMID- 14963355
TI  - Pneumatic lithotripsy through pyelotomy incision during open surgery for staghorn
      calculi: an alternative method to anatrophic nephrolithotomy.
AB  - INTRODUCTION: Our purpose was to remove large-volume staghorn calculi with less
      morbidity and maximum ease without an anatrophic nephrolithotomy, with the use of
      a pneumatic lithotriptor during pyelolithotomy to disintegrate the branches of
      stones extending into the calyces and retained calyceal fragments. PATIENTS AND
      METHODS: Sixteen patients (17 renal units) with large-volume staghorn stones were
      evaluated with blood urea nitrogen (BUN), creatinine levels, urinalysis, and
      culture, excretory urography (IVP), and 99mtechnetium dimercaptosuccinic acid
      (DMSA) renal scintigraphy preoperatively. Patients were treated with a pneumatic
      lithotriptor at the time of open pyelolithotomy. Bilateral surgery was performed
      in 1 patient. The mean follow-up period was 12 (range 6-24) months. The patients
      were re-evaluated postoperatively at 6 months with BUN and serum creatinine
      measurements, urinalysis and culture, IVP, and renal scintigraphy with DMSA. Data
      were analyzed by one-way ANOVA test. p < 0.05 was considered statistically
      significant. RESULTS: After treatment, 15 of 17 renal units (88%) were rendered
      stone-free while residual fragments remained in two patients. Average operation
      time was 190 min (range 135-285) with a mean blood loss of 226 ml (range 140
      425). No patient required blood transfusion. Average length of hospital stay was
      4.2 days (range 3-7). Six months after surgery, mean BUN and creatinine levels
      were decreased from 31.2 to 28.2 mg/dl (p = 0.248) and from 1.3 to 1.1 mg/dl (p =
      0.001), respectively. Renal scintigraphy with DMSA revealed an increase in
      ipsilateral average renal function from 39 to 43% (p = 0.043). IVP also revealed
      a decrease in pelvicalyceal dilatation in almost all patients with a well
      functioning kidney and without any stone recurrence. No complications were
      encountered postoperatively except for an episode of high fever in 1 patient.
      CONCLUSION: Avoiding incision of the renal parenchyma and arterial clamping,
      without significant bleeding and the nephron loss seem to be the advantages of
      this technique. Kidney function can be preserved with this simple and easily
      applicable method, which may be an alternative procedure to anatrophic
      nephrolithotomy for the majority of patients with staghorn calculi requiring open
      surgery.

PMID- 14963356
TI  - Intravesical vanilloids and neurogenic incontinence: ten years experience.
AB  - INTRODUCTION: In this study we critically review our '10-year' experience with
      intravesical vanilloids (capsaicin and resiniferatoxin) in the treatment of
      neurogenic incontinence, addressing the issue of their introduction into daily
      clinical practice. MATERIALS AND METHODS: From July 1992 to June 2001, 54
      patients suffering from detrusor hyperreflexia, due to spinal cord injuries,
      received intravesical instillation of capsaicin, and from January 1995 to June
      2001, 47 patients received intravesical instillation of resiniferatoxin (RTX) in
      order to treat bladder dysfunction and symptoms. All patients presented detrusor
      hyperreflexia refractory to oral and/or intravesical oxibutynin and they
      displayed high-voiding pressure associated with frequent urine leakage. Capsaicin
      was used at a concentration of 10 mM; RTX was tested in two different
      concentrations: 10 nM and 10 microM. The outcome was considered according to
      simple parameters: (i) the number of patients who reported an improvement in
      clinical status (patient dry between clean intermittent catheterization) and
      urodynamic status (a bladder capacity 50% higher than pretreatment capacity,
      lasting more than 3 months after the instillation); (ii) the number of patients
      who continued intravesical therapy; (iii) the number of instillations they
      received; (iv) the length of the interval between 2 consecutive instillations,
      and (v) alternative therapies when vanilloids failed. RESULTS: The topical
      intravesical instillation of capsaicin produced an improvement in symptoms and
      urodynamic parameters, in 29 patients (53.7%) after 3 months. In these 29
      patients only 7 (24.13%) continued to received capsaicin in June 2001. The mean
      follow-up was 32.28 +/- 14.20 (range 8-52) months, the mean number of
      instillations was 6.14 +/- 2.54 (range 2-10) and the mean interval between the 2
      consecutive instillations was 7.14 +/- 2.60 (range 4-12) months. The topical
      intravesical instillation of RTX produced an improvement in symptoms and
      urodynamic parameters in 73.33% of patients (a total of 45 patients) who received
      10 microM. 18 of them (54.54%) continued to received RTX in June 2001. The mean
      follow-up was 27.88 +/- 10.95 (range 11-49) months, the mean number of
      instillations was 4.33 +/- 1.60 (range 2-8). The mean interval between 2
      consecutive instillations was 9.61 +/- 2.99 (ranged 4-16) months. CONCLUSION: The
      results obtained using RTX seem to be very promising with regard to efficacy and
      tolerance, particularly in comparison with capsaicin. Even if the number of
      patients who received capsaicin and RTX remains small, the intravesical vanilloid
      receptor agonist RTX could offer an attractive alternative to oral medications in
      the treatment of neurogenic incontinence.

PMID- 14963357
TI  - Percutaneous therapy of varicocele: effects on semen parameters in young adults.
AB  - BACKGROUND: In spite of many years of debate, the impact of varicocele on male
      infertility is still controversial since its pathogenetic role on the impairment
      of semen quality has never been fully demonstrated. METHODS: In the present work,
      a series of 426 young adult males undergoing percutaneous treatment of varicocele
      were studied and semen parameters were evaluated at baseline and 12 months of
      follow-up. RESULTS: A significant increase in sperm cell concentration and a
      decrease in immotile spermatozoa were found after varicocele repair, but we
      failed to detect any significant positive change in progressive motility as well
      in sperm morphology after treatment. Similar results were also obtained when
      semen parameters were correlated with the degree of varicocele. CONCLUSION: Since
      a spontaneous improvement in semen quality has been mathematically established as
      a model of regression toward the mean, we conclude that the correction of
      varicocele in young adults is not a major indication when semen alteration is the
      only clinical problem.

PMID- 14963358
TI  - Electronic data base systems support the evaluation of male infertility factors,
      example cryptorchidism.
AB  - BACKGROUND: A new data base system was applied to analyse our patient group with
      two aims: (a) to analyze the effects of former cryptorchidism on the fertility of
      OUR infertility patients in comparison with the data of the literature and (b) to
      evaluate this system in a clinical study. MATERIALS AND METHODS: Using the
      electronic data base Winsperm 2000, 1,648 infertility patients, 79 patients with
      testicular cancer and 201 healthy semen donors were examined. RESULTS: A history
      of cryptorchidism, treated at 6.8 +/- 3.3 years of life, was found in 10.1% of
      our infertility patient group. The routine spermiogram parameters, as well as
      basal hormone concentration of FSH, LH and testosterone, differed significantly
      from those of the healthy semen donor group. Comparison between patients with
      former unilateral and bilateral cryptorchidism differed significantly only in
      total sperm count. 27.7% of patients with a history of unilateral and 5.4% of
      patients with a history of bilateral cryptorchidism showed a sperm concentration
      within the normal range (p < 0.01). Azoospermia was detected in 13.1% of patients
      with unilateral cryptorchidism and in 29.7% of patients with former bilateral
      cryptorchidism (p < 0.05). The patients responding to our conception
      questionnaire realised a total conception rate of 46.1% in the 'non
      cryptorchidism group' and of 20.6% in the 'cryptorchidism-group' (p < 0.05),
      whereas the conception rates did not differ between former unilateral and
      bilateral cryptorchidism (p > 0.05). Sixteen (20.3%) of the 79 patients with
      testicular neoplasm were previously treated for cryptorchidism. CONCLUSION: The
      results of our patient group underline the significance of former cryptorchidism
      for infertility and testicular neoplasm. The new data base system facilitates
      rapid data retrieval and examination.

PMID- 14963359
TI  - A novel surgical approach to subinguinal varicocelectomy: artery and lymphatic
      isolation technique.
AB  - Clinically relevant varicoceles require surgical management through one of
      several techniques. We introduce an innovative technique for varicocelectomy via
      a subinguinal approach that allows identification and preservation of the
      arteries and lymphatics. This method allows the safe excision of the varicocele,
      while minimizing the risk of complications.

PMID- 14963360
TI  - Mini-invasive management of a rare complication of percutaneous stone treatment:
      entrapped nephrostomy tube.
AB  - A case of entrapped nephrostomy tube in a 61-year-old woman who underwent
      percutaneous nephrolithotomy and subsequent multiple ESWL for a left staghorn
      stone is presented. A nephrostomy track was created alongside the Malecot
      catheter and the overgrown tissue which was bridging the wings of the tube was
      incised with a Sachse urethrotome. To prevent this complication the wings of the
      Malecot should freely expand in the renal collecting system and the catheter
      should stay in situ for no more than 3 weeks.

PMID- 14963361
TI  - Unusual double primary neoplasia: adrenocortical and ureteral carcinomas in
      werner syndrome.
AB  - Adrenocortical and ureteral carcinomas were observed in a 50-year-old Japanese
      woman with Werner syndrome (MIM No. 27770). The syndrome is an autosomal
      recessive disorder characterized by premature aging and an increased risk of rare
      cancers, which are often multiple. This is the first reported association of
      adrenocortical carcinoma in Werner syndrome.

PMID- 14963362
TI  - A case of renal cell carcinoma with a natural history of 13 years.

PMID- 14963363
TI  - Renal cell cancer in presacral ectopic kidney: preoperative diagnostic imaging
      compared to surgical findings.
AB  - The occurrence of renal cell carcinoma is an exceptional phenomenon in an ectopic
      kidney. We describe a patient with renal cell cancer of the pelvic kidney who
      underwent radical nephrectomy at our institute. Preoperatively the patient
      underwent paramagnetic medium-enhanced magnetic resonance that provided an
      accurate description of the ectopic renal vessels. During surgery the anatomy of
      the vessels appeared exactly as described by the MR examination. Histological
      examination revealed a pT2N0GIV renal cell cancer. Nine months later the patient
      underwent control examinations, and no delayed complications had occurred. In our
      experience magnetic resonance provided an exact description of the ectopic kidney
      vascularization as confirmed by the surgical findings. Preoperative knowledge is
      important both for the surgeon during the dissection of the vessels and to plan
      correct lymphadenectomy on the basis of the vessel source identified at imaging.

PMID- 14963364
TI  - Primary transitional cell carcinoma of the prostate presenting as a rectal ulcer.
AB  - Primary transitional cell carcinoma of the prostate is a rare clinicopathological
      entity. It is an aggressive tumor with a poor prognosis. Presentation is usually
      late, with obstructive voiding complaints. Radical surgery offers locoregional
      control of the disease. We report a case with an atypical presentation of
      bleeding per rectum and associated obstructive voiding symptoms. Examination
      revealed a rectal ulcer overlying an enlarged prostate and fixed to it.
      Histopathology showed a picture of transitional cell carcinoma of the prostate
      infiltrating the rectum. Imaging studies revealed an enlarged prostate with
      altered echo pattern with locoregional spread, infiltrating the rectum. Bladder
      involvement and distant metastases were not evident. External beam radiotherapy
      achieved good local control. At 3 months of follow-up, the patient was free of
      urinary symptoms and his rectal ulcer had healed. The patient declined subsequent
      treatment.

PMID- 14963365
TI  - 'Undo-Allo' stem cell transplantation: another concept to control allogeneic
      immunotherapy?

PMID- 14963366
TI  - Mosquito allergy: immune mechanisms and recombinant salivary allergens.
AB  - Reactions to mosquito bites are immunological in nature, with the involvement of
      IgE-, IgG- and T lymphocyte-mediated hypersensitivities. Acquired desensitization
      to mosquito saliva may occur during childhood and adolescence or during long-term
      exposure to mosquito bites. Due to the lack of salivary preparations, allergic
      reactions to mosquito bites are underdiagnosed and undertreated. Recombinant
      mosquito saliva allergens with biological activity are being developed. These
      recombinant allergens will significantly improve diagnosis of mosquito allergy
      and eventually will also improve specific immunotherapy for patients with
      systemic reactions to mosquito bites.

PMID- 14963367
TI  - From bone biology to bone analysis.
AB  - Bone development is one of the key processes characterizing childhood and
      adolescence. Understanding this process is not only important for physicians
      treating pediatric bone disorders, but also for clinicians and researchers
      dealing with postmenopausal and senile osteoporosis. Bone densitometry has great
      potential to enhance our understanding of bone development. The usefulness of
      densitometry in children and adolescents would be increased if the physiological
      mechanisms and structural features of bone were given more consideration in the
      design and interpretation of densitometric studies. This review gives an overview
      on the most relevant techniques of quantitative noninvasive bone analysis.
      Furthermore it describes the relationship between bone biology, selected
      surrogates describing the biological processes and the possibilities of measuring
      these surrogates specifically and precisely by the different devices. The overall
      recommendation for researchers in this field is to describe firstly the
      biological process to be analyzed (bone growth in length, remodeling or modeling,
      or all together), secondly the bone parameter which describes this process, and
      thirdly the reason for selecting a special device.

PMID- 14963368
TI  - Alteration of integrins under hypoxic stress in early placenta and
      choriocarcinoma cell line BeWo.
AB  - Invasion of the trophoblast into the decidua and the myometrium is very important
      for the establishment of a normal pregnancy. This invasion is regulated by the
      expression of integrins in the trophoblast. Recently, it has been shown that
      invasion of the trophoblast is impaired in preeclampsia. We report the effect of
      hypoxia on the expression of integrins and extracellular matrices at the mRNA
      level in early placenta and BeWo cells. Tissue RNA levels of fibronectin and
      integrin alpha5 were significantly higher in the hypoxic condition than under
      normoxic conditions. In contrast, tissue RNA levels of integrin alpha1 were
      significantly lower for the hypoxic condition than those under normoxic
      conditions. Alteration of the integrin components and increases in fibronectin
      expression were observed in early placenta and BeWo cells under hypoxic
      conditions. These results suggest that hypoxic stress regulates the synthesis of
      integrin and fibronectin mRNAs in early placenta.

PMID- 14963369
TI  - Association of the TNF2 allele with eclampsia.
AB  - The genetic background predisposing pregnant women to the disorder pre
      eclampsia/eclampsia (PE/E) is still unknown. There is compelling evidence to
      suspect involvement of the immune system in the development of PE/E. The aim of
      this current study was to investigate whether there is an association between the
      tumor necrosis factor (TNF)-alpha -307 polymorphism and PE or eclampsia. In this
      study, 51 cases of eclampsia, 122 cases of PE and 100 normotensive control cases
      were genotyped for the TNF-alpha -307 polymorphism. We found a significant
      difference between the TNF2 allele frequencies of eclamptic and normotensive
      controls (chi(2) = 6.3 and p = 0.025), but not of pre-eclamptic and normotensive
      controls (chi(2) = 0.5 and p = 1.0). We conclude from this study that the TNF2
      allele contributes to the occurrence of eclampsia in our population.

PMID- 14963370
TI  - Insulin-like growth factor 1 receptor mRNA expression and autophosphorylation in
      human myometrium and leiomyoma.
AB  - Uterine leiomyomas are the most common tumors of the genital tract. Growth
      factors seem to be implicated in the development of leiomyoma. The aim of this
      study was to determine insulin-like growth factor 1 receptor (IGF-1-R) mRNA
      levels and IGF-1-R tyrosine kinase activity in normal myometrium and leiomyoma.
      Plasma membranes of myometrium and leiomyoma of 14 women subjected to
      hysterectomy were prepared, and samples were incubated in the absence or presence
      of recombinant human IGF-1 to assess the tyrosine kinase activity (Western blot).
      Reverse-transcriptase polymerase chain reaction with specific primers for IGF-1-R
      was used to determine IGF-1-R mRNA levels. IGF-1-R mRNA levels in myometrium
      (0.8216 +/- 0.096) and in leiomyoma (0.7905 +/- 0.136) were not statistically
      significantly different (p = 0.648). The degree of IGF-1-R autophosphorylation
      stimulated by recombinant IGF-1 was not different in myometrium (1.020 +/- 0.120)
      and leiomyoma (1.620 +/- 0.656) either (p = 0.075). There was no difference in
      IGF-1-R expression and IGF-1-R autophosphorylation between normal myometrium and
      leiomyoma.

PMID- 14963371
TI  - Strategies for the laboratory diagnosis of some common causes of anaemia in
      elderly patients.
AB  - Anaemia is a common medical problem in elderly patients and is associated with an
      increased mortality and morbidity risk and a reduced quality of life. It is not
      known at which exact haemoglobin level investigations should be initiated in
      order to optimize the diagnostic efficacy. Serum ferritin determination remains
      the most accurate laboratory test for the diagnosis of iron deficiency anaemia
      and its differential diagnosis with the anaemia of chronic disease. The
      introduction of the metabolites methylmalonic acid and homocysteine has made it
      possible to diagnose vitamin B(12) and folate deficiencies at an early
      subclinical stage, even without neurological and haematological symptoms, but the
      clinical importance of this 'biochemical' diagnosis is unclear. Other causes of
      anaemia, such as myelodysplastic syndromes and chronic renal insufficiency, will
      become more and more common in the elderly because of the ageing of the
      population. Although erythropoietin analysis has no clear diagnostic value at the
      moment, it has become more and more obvious that its therapeutic importance in
      elderly patients with chronic anaemia is increasing. A substantial number of
      patients have an unexplained anaemia. Whether this is disease related, or may be
      attributed to an age-related anaemia, is still a matter of debate, but it is
      advisable to perform an extensive laboratory, cytogenetic, and morphological
      investigation before one should assess the anaemia as unexplained.

PMID- 14963372
TI  - Accumulation of 8-oxo-2'-deoxyguanosine (as a biomarker of oxidative DNA damage)
      in the tissues of aged hamsters and change in antioxidant enzyme activities after
      single administration of N-nitrosobis(2-oxopropyl) amine.
AB  - BACKGROUND: It has been reported that DNA oxidative damage accumulates with age.
      Two reasons for this phenomenon are the decline in the antioxidant system and the
      decline in the repair system. It is not clear which of these is the main reason.
      OBJECTIVE: To study whether the decline in antioxidant enzyme activities causes
      the accumulation of DNA oxidative damage, an experimental study was performed
      with hamsters. METHODS: Seventy-four female Syrian golden hamsters were divided
      into 2 groups: a young group (28 hamsters), and an aged group (46 hamsters). The
      hamsters in the aged group were kept in our laboratory until they were 18 months
      old. The levels of 8-oxo-2'-deoxyguanosine (8-oxodG) and the activities of
      antioxidant enzymes, i.e. catalase, superoxide dismutase (SOD), and glutathione
      peroxidase (GPx), were measured in both groups. Furthermore, the same parameters
      were measured in the pancreas and liver following administration of N
      nitrosobis(2-oxopropyl)amine (BOP), an inducer of oxidative stress in the hamster
      pancreas. RESULTS: In the mid brain, cerebellum, lung, heart, spleen and kidney,
      the 8-oxodG contents in aged hamsters were significantly higher than those in
      young hamsters. GPx activity decreased with age in the lung, liver and kidney,
      whereas SOD activity increased in the lung and liver but decreased in the kidney
      of aged animals. Catalase activity increased in the cerebrum, heart, pancreas and
      kidney but decreased in the lung and spleen of aged hamsters. When the pancreatic
      levels of 8-oxodG and antioxidant enzymes were measured after BOP administration,
      there was no clear-cut relation between the changes in those levels. CONCLUSIONS:
      From these results the increase in 8-oxodG contents in aged hamsters does not
      seem to be related to the antioxidant system but rather to a possible decline in
      the repair system against oxidative damage.

PMID- 14963373
TI  - Biological age and 12-year cognitive change in older adults: findings from the
      Victoria Longitudinal Study.
AB  - BACKGROUND: Although recent cross-sectional findings indicate that markers of
      biological age (BA) mediate chronological age (CA) differences in cognitive
      performance, little is known about their influence on actual cognitive changes.
      OBJECTIVE: The purpose of this investigation is to examine CA and BA as
      predictors of 12-year cognitive change in a longitudinal sample of older adults.
      METHODS: Data from the Victoria Longitudinal Study (VLS) were examined for 125
      adults between 67 and 95 years of age. Biomarkers, including visual and auditory
      acuity, grip strength, peak expiratory flow, blood pressure, and body mass index,
      were submitted to a factor analysis and a composite BA variable was computed
      based on factor loadings. Intraindividual change across 5 waves of measurement (3
      year intervals) was examined as a function of CA and BA for 5 cognitive domains:
      verbal processing speed, working memory, reasoning, episodic memory, and semantic
      memory. RESULTS: The latent structure of biomarkers was consistent with previous
      investigations of functional age and a common factor view of biological aging.
      Results of hierarchical linear modeling showed that BA predicted actual cognitive
      change (decline) independent of CA. CONCLUSIONS: As a predictor of cognitive
      performance in late life, CA is a proxy for biological and environmental
      influences. We have shown that biological influences are independent predictors
      of actual cognitive change in older adults. This supports the view that cognitive
      decline is not due to aging per se, but rather is likely due to causal factors
      that operate along the age continuum.

PMID- 14963374
TI  - Health-related quality of life in patients over sixty years old with benign
      paroxysmal positional vertigo.
AB  - BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is a common cause of
      dizziness within the geriatric population causing disability. The diagnosis is
      established by the position-induced rotatory nystagmus, related to the involved
      ear, demonstrated by the Dix-Hallpike test (DHT). Although the Epley's modified
      manoeuvre, or particle respositioning manoeuvre (PRM), is an effective treatment
      for this disorder, its impact on health outcome in patients over 60 years old is
      unknown. OBJECTIVE: To assess BPPV health-related quality of life in elderly
      individuals using the Medical Outcomes Study 36-Item Short Form Health Survey (SF
      36) and the Dizziness Handicap Inventory Short Form (DHI-S). METHODS: A
      prospective study including new cases of BPPV in patients older than 60 years was
      carried out. The diagnosis was based on the history of recurrent sudden crises of
      vertigo and a typical positional-induced nystagmus during the DHT. All patients
      were treated by a single PRM and relapses were investigated a the 30th post
      treatment day. RESULTS: DHT was found negative in 82% (23/28) individuals at 30
      days. The eight scales of the SF-36 have a good internal consistency reliability
      in patients with BPPV (Cronbach's alpha > 0.7). The average standardized score
      for each SF-36 scale was compared with the reference population normative data,
      showing differences with norms for role physical, body pain, social function,
      role emotional and mental health. After PRM, patients restored scores to norms,
      showing a significant increase in role physical (p < 0.05), body pain (p < 0.04),
      vitality (p < 0.02), social function (p < 0.003) and mental health scores (p <
      0.005). DHI-S total score significantly decreased from 17.19 +/- 9.06 (mean +/-
      SD) at the first day to 9.70 +/- 10.13 at 30 days (p < 0.001). CONCLUSIONS: BPPV
      has a significant impact on health-related quality of life in elderly patients on
      their emotional and physical states compared to those unaffected. The PRM can
      restore health-related quality of life in elderly patients with BPPV.

PMID- 14963375
TI  - Changes in postural balance in frail elderly women during a 4-week visual
      feedback training: a randomized controlled trial.
AB  - BACKGROUND: Balance training programs have not shown consistent results among
      older adults, and it remains unclear how different training methods can be
      adapted to frail elderly people. OBJECTIVE: The purpose of this study was to
      investigate the effects of a 4-week visual feedback-based balance training on the
      postural control of frail elderly women living in residential care homes.
      METHODS: Elderly women of two residential care facilities were randomized to an
      exercise group (EG, n = 20) and to a control group (CG, n = 7). The EG
      participated in training sessions three times/week for 4 weeks. The exercises
      were carried out with a computerized force platform with visual feedback screen.
      The dimensions of balance function studied were standing body sway, dynamic
      weight shifting, and Berg Balance Scale performance. RESULTS: The EG showed
      significant improvement in balance functions. The performance time in dynamic
      balance tests improved on average by 35.9% compared with a 0.6% increase in the
      CG (p = 0.025-0.193). The performance distance in these tests decreased on
      average by 28.2% in the EG as compared with a 9.8% decrease seen in the CG. The
      Berg Balance Scale performance improved by 6.9% compared with a 0.7% increase in
      the CG (p = 0.003). The standing balance tests in the more demanding standing
      positions showed improvements in the EG, whereas similar changes in the CG were
      not found. CONCLUSIONS: Our findings suggest that balance training based on
      visual feedback improves the balance control in frail elderly women living in
      residential care, also enhancing the performance of functional balancing tasks
      relevant to daily living. The subjects were motivated to participate in the
      training, as indicated by the high compliance (97.5%) with the program.

PMID- 14963376
TI  - Prevalence of remediable disability due to low vision among institutionalised
      elderly people.
AB  - BACKGROUND: Prevalence of remediable visual disability among institutionalised
      elderly people, resulting from inappropriate use or non-use of low-vision aids,
      is reported to be high, but largely rests on anecdotal evidence. OBJECTIVE: To
      estimate the prevalence of binocular low vision and underlying eye diseases among
      institutionalised elderly people in a Dutch urban population and the size of
      remediable visual disability as the result of inappropriately corrected low
      vision. METHODS: The design was a cross-sectional survey of 284 subjects with low
      vision (corrected binocular vision <0.4) in nursing homes and homes for the
      elderly in the Netherlands. RESULTS: 284 of 610 eligible residents were examined.
      The prevalence of binocular low vision was 31.3%. Among elderly residents with
      low vision, prevalence of cataract, age-related macular degeneration, glaucoma,
      and diabetic retinopathy was 77.9, 37.7, 5.2 and 5.2%, respectively. In 32
      residents (41.6%), (non)-use of low-vision aids was considered inappropriate. In
      50 residents (64.9%), visual disability was considered at least partially
      remediable, either through better use of low-vision aids, or through cataract
      extraction. Residents who were not optimally corrected for low vision were
      significantly more functionally impaired compared with their peers who were
      optimally corrected. CONCLUSION: Low vision is likely to be highly prevalent
      among institutionalised elderly. A significant amount of the associated visual
      disability may be remediable.

PMID- 14963377
TI  - Predictors of early neurological deterioration after ischaemic stroke: a case
      control study.
AB  - BACKGROUND: Early neurological deterioration after ischaemic stroke (stroke in
      progression) is reported to be common and associated with poor outcome or death.
      The causes of progressing stroke are, however, uncertain. OBJECTIVE: To determine
      whether prior drug treatment (with anticoagulant or antiplatelet agents) or early
      adverse physiological features (pyrexia, hypoxia, dehydration or hyperglycaemia)
      are associated with progressing ischaemic stroke. METHODS: The study used a case
      control design. From a database of 873 consecutive acute stroke admissions, 196
      cases of progressing ischaemic stroke (defined by point deterioration in
      components of the Scandinavian Stroke Scale or death over the first 72 h after
      hospital admission) were matched to 196 controls on the basis of age and stroke
      type. Univariate and conditional logistic regression techniques were used to
      explore predictors of progressing stroke. RESULTS: Cases and controls were well
      matched for baseline stroke severity. Warfarin use prior to admission was
      associated with a reduced risk of progressing stroke [odds ratio (OR) 0.10, p =
      0.005]. Prior antiplatelet use was not related. A previous history of diabetes
      (OR 2.11, p = 0.039) and elevated systolic blood pressure on admission (OR 1.01
      for each 1 mm Hg rise, p = 0.017) predicted progressing stroke. Although there
      were no differences in time to presentation or to brain imaging, a visible
      causative lesion on CT scanning was more common in the progressing stroke group
      (OR 2.30, p = 0.022). We found no evidence that adverse physiological features
      were associated with progressing stroke. Outcomes were worse in the progressing
      stroke group with 70% being dead or dependent by 30 days compared to 55% in the
      control group (p = 0.002). CONCLUSION: Prior warfarin use may be protective
      against progressing ischaemic stroke. A previous history of diabetes along with
      elevated admission systolic blood pressure predict deterioration. We found no
      evidence for an association between adverse physiological features and
      progressing stroke.

PMID- 14963378
TI  - Effects of dementia on mortality in the radiation effects research foundation
      adult health study.
AB  - BACKGROUND: Although dementia is rarely listed on death certificates, it does
      contribute to mortality. The predominant immediate causes of death coincident
      with dementia are pneumonia and cardiovascular diseases. OBJECTIVE: To estimate
      the impact of dementia on specific mortality risks. METHODS: We applied DSM-III/R
      criteria for Alzheimer's disease (AD) and vascular dementia (VaD) to 2,172
      subjects of the Adult Health Study of the Radiation Effects Research Foundation
      who were 60 or more years old when examined from 1992 to 1996. The underlying
      causes of death were compiled from death certificates. We performed a Poisson
      regression analysis to evaluate specific causes of mortality for which AD or VaD
      was a significant risk factor. RESULTS: The relative risk of mortality was 2.2
      for AD and 2.4 for VaD. Mortality from pneumonia and stroke was elevated for both
      types of dementia, independent of other medical conditions. AD was also
      associated with death from trauma. CONCLUSION: Dementia was a predictor of death
      due to pneumonia, stroke, and trauma among the Japanese elderly. The prevention
      and early detection of those conditions are important in the medical care and
      treatment of dementia cases.

PMID- 14963379
TI  - Nursing homes for the old ('Gerocomeia') in Byzantium (324-1453 AD).
AB  - BACKGROUND: Research into the welfare institutions for the elderly, which were
      established in the Byzantine Empire. OBJECTIVE: The purpose of the study is the
      research into the texts of the Byzantine chroniclers and the contemporary
      historical sources so as to determine the social policy of the Byzantine State
      regarding the homes for the aged. METHODS: The histories and chronicles of the
      Byzantine writers, written in the original Greek language, were studied and
      analysed, so as to locate the extracts in the texts concerning the interest shown
      by the Byzantine State to establish institutions for old and ailing people.
      RESULTS: The care for the elderly in Byzantium was undertaken in special
      infirmaries, called 'gerocomeia', which operated all over the empire mostly in or
      near the monasteries. All these nursing homes were highly esteemed and the
      governor of the institution seems to have been a person of high importance. The
      most important nursing home was located in Constantinople and was established by
      Emperor John II Comnenus in the 12th century in the famous monastery and hospital
      of the Pantocrator. CONCLUSION: The study and analysis of the historical texts of
      the Byzantine period (324-1453 AD) prove that human-oriented behaviour, which
      derived from the intervention of religion, contributed to the foundation of many
      welfare institutions for the elderly by the Byzantine emperors, the church and
      some individuals who showed great interest in them.

PMID- 14963380
TI  - Characteristics of falls producing hip fracture in an elderly population.

PMID- 14963381
TI  - Carotid plaque echomorphology and serum vascular endothelial growth factor
      levels.
AB  - Neovascularization in atherosclerotic plaques plays an essential role in the
      progression and rupture of plaques. Vascular endothelial growth factor (VEGF) is
      an important angiogenic factor. Echomorphologic evaluation of carotid plaques
      using computer-assisted imaging was found to have a good correlation with the
      histology of the lesion. The aim of this study was to investigate whether the
      serum VEGF level could be a determinant of the echomorphology of the carotid
      plaque. In 28 carotid plaques causing 60-99% stenosis, serum VEGF levels and the
      mean gray value (MGV) of three-dimensional image of the carotid plaques were
      measured. A statistically significant inverse correlation was found between serum
      VEGF concentrations and MGVs (Spearman's correlation coefficient: -0.415, p =
      0.028). Our finding indicates that in patients with > or =60% carotid stenosis
      the serum VEGF levels are associated with the echogenicity of the atherosclerotic
      plaque.

PMID- 14963382
TI  - MR signal changes in a child with cat scratch disease encephalopathy and status
      epilepticus.

PMID- 14963383
TI  - Vertebral artery dissection complicated by a thrombosis of the basilar artery was
      successfully treated with endovascular thrombolysis.

PMID- 14963384
TI  - May intracranial hypotension be a cause of venous sinus thrombosis?

PMID- 14963385
TI  - Selective impairment of the auditory-verbal short-term memory due to a lesion of
      the superior temporal gyrus.

PMID- 14963386
TI  - Amnesia following endoscopic third ventriculostomy: a single case study.

PMID- 14963387
TI  - Striatocapsular infarction caused by middle cerebral artery dissection.

PMID- 14963388
TI  - Diagnosis of vascular compression at the thoracic outlet using magnetic resonance
      angiography.

PMID- 14963389
TI  - Parageusia: an unusual presentation of multiple sclerosis.

PMID- 14963390
TI  - [Evaluation of patello-femoral joint congruity following total knee
      arthroplasties].
AB  - OBJECTIVES: Complications associated with the patellar component have an
      important place for revision procedures following total knee arthroplasty (TKA).
      We evaluated the patello-femoral congruity both clinically and radiologically
      after TKAs performed with polyethylene patellar components. METHODS: The study
      included 60 knees of 55 patients (45 females, 10 males; mean age 66 years; range
      33-82 years). Clinically, all patients were evaluated with respect to pain, knee
      functions, and range of motion of the knee joint. Antero-posterior, lateral, and
      patellar tangential radiographs were obtained. According to the tangential
      radiographs, the patients were divided into three groups; normal (group A),
      abnormal angular values without subluxation (group B), and the existence of
      subluxation, dislocation, or a fracture (group C). Patellar height, variations in
      the joint line, and patellar coverage by the component were measured on lateral
      radiographs. Patients with normal patellar congruity and patellar subluxation
      were compared. The mean follow-up period was 40 months (range 12 to 88 months).
      RESULTS: No significant differences were found between the three groups with
      respect to pain and range of motion of the knee joint; however, functional scores
      differed significantly (p=0.019). Radiologically, the mean valgus angles were not
      significantly different. According to the location of the patellar component on
      tangential radiographs, group A, group B, and group C included 39 knees (65.0%),
      11 knees (18.3%), and 10 knees (16.7%), respectively. Measurements on lateral
      radiographs did not yield significant differences between patients with normal
      patellar congruity and patellar subluxation. CONCLUSION: Patellar subluxation
      should be investigated on tangential radiographs following TKA because lateral
      radiographs of the knee fail to show patello-femoral problems.

PMID- 14963391
TI  - [The effects of surgical margins on local control and survival in extremity soft
      tissue sarcomas].
AB  - OBJECTIVES: We evaluated the effects of surgical margins and other prognostic
      factors on local control and survival in extremity soft tissue sarcomas. METHODS:
      The study included 40 patients (34 males, 6 females; mean age 45 years; range 13
      to 77 years) who underwent treatment for extremity soft tissue sarcomas. Of
      these, 14 patients presented with recurrences following treatment elsewhere.
      Preoperatively, nine patients and eight patients; postoperatively, 35 patients
      and 25 patients received radiotherapy and chemotherapy, respectively. Limb
      salvaging surgery was performed in 35 patients (87.5%), of whom 28 patients (70%)
      received an extended resection, and seven patients received a marginal resection.
      Five patients (12.5%) required amputation. Negative surgical margins were
      achieved in 34 patients (85%), while six patients (15%) had positive surgical
      margins. The mean follow-up period was 58 months (range 13 to 124 months).
      RESULTS: Five patients (12.5%) developed local recurrences following marginal
      resection (n=4), and amputation. No local recurrences were seen in patients
      receiving an extended resection or in those having negative surgical margins.
      Five-year survival rates were 51% and 49% in patients whose initial diagnoses
      were made in our department and elsewhere, respectively. Significant correlations
      were found between extended resection (p=0.0001) and negative surgical margins
      (p=0.0001) and local control; and between tumor grade and survival (p=0.002).
      Positive surgical margins and local recurrences did not decrease survival.
      CONCLUSION: Achievement of negative surgical margins promotes local control in
      extremity soft tissue sarcomas. A careful preoperative planning and utilization
      of neoadjuvant therapies highly increase the possibility of negative surgical
      margins.

PMID- 14963392
TI  - [Correlation of clinical and radiologic results of complete subtalar release in
      congenital clubfoot].
AB  - OBJECTIVES: We evaluated the mid-term results in patients who underwent complete
      subtalar release with the use of the Cincinnati incision for congenital clubfoot.
      METHODS: Complete subtalar release was performed in 30 feet of 23 patients (16
      boys, 7 girls; 7 bilateral cases). The mean age at surgery was 17.5 months (range
      2 to 84 months). Clinically, cosmetic appearance, adduction of the forefoot, the
      range of motion of the ankle joint, and muscle strength were evaluated.
      Radiologic evaluations included talocalcaneal angles on antero-posterior and
      lateral views, talocalcaneal index, talar-first metatarsal angles, calcaneal
      fifth metatarsal angles, and Bohler angles. Talar and navicular bone lengths were
      compared with the other side in unilateral patients. The results were evaluated
      according to the Simons' criteria. The mean follow-up was 9 years and 8 months
      (range 7 years to 14 years). RESULTS: The mean range of motion of the ankle joint
      was measured as 47 degrees (range 10 degrees to 60 degrees ). The parents of
      three patients were not satisfied with the clinical results. Clinically, six
      patients had metatarsus adductus. Radiologically, flattening of the talar head (7
      patients) and the talar dome (2 patients) were detected in unilateral patients.
      Navicular dorsal subluxation was found in seven feet. Compared to the normal
      side, the mean navicular shortening was 2.6 mm (range 0 to 4 mm), the mean talar
      shortening was 4.8 mm (range 2 to 11 mm). According to the Simons' criteria, the
      results were satisfactory in 27 feet (90%) and unsatisfactory in three feet
      (10%). CONCLUSION: Our results suggest that complete subtalar release for the
      treatment of clubfoot enables correction of all components of the deformity at a
      single session, and that its clinical results are more favorable than radiologic
      results, without requiring a close cooperation of the parents.

PMID- 14963393
TI  - [Flexor tendoplasty with a tendon prosthesis for zone II flexor tendon injuries].
AB  - OBJECTIVES: We evaluated two-staged flexor tendoplasty with tendon prosthesis in
      patients with flexor tendon injuries in which conventional tendon grafting would
      fail to yield an acceptable result. METHODS: We performed flexor tendoplasty with
      tendon prosthesis in 37 hands of 31 patients (24 males, 7 females; mean age 23
      years; range 4-46 years). Twenty-six patients had penetrating injuries, four had
      occupational injuries, and one patient had an electric burn. Preoperatively, all
      patients were evaluated according to the Boyes' classification. At the first
      stage, a silicone prosthesis, 4-6 mm in diameter was placed according to the
      patient's age and the recipient bed; after 3 to 5 months, silicone prosthesis was
      removed and flexor tendoplasty with a tendon graft was performed. The results
      were calculated according to the Strickland's formula. The mean follow-up period
      after the second operation was 37 months (range 12-80 months). RESULTS: The
      results were excellent in 11 hands (Strickland 75-100%), good in 15 hands (50
      74%), moderate in nine hands (25-49%), and poor in two hands (0-24%), with a mean
      of 58%. Tenolysis was performed in seven patients at least four months after the
      second stage. Removal of the tendon prosthesis was required in one patient
      because of infection. CONCLUSION: Satisfactory results can be obtained with two
      staged flexor tendoplasty with a tendon prosthesis in patients with joint
      injuries restricting finger movements, digital nerve injuries causing trophic
      changes in the finger, and multiple tissue injuries.

PMID- 14963394
TI  - [The management of size discrepancies in microvascular anastomoses].
AB  - OBJECTIVES: Microvascular anastomosis is the main component of flap transfer and
      replantation surgery. The aim of this study was to evaluate size discrepancies
      encountered during microvascular surgery, techniques to handle the problems, and
      the results of anastomoses performed. METHODS: We evaluated 99 microsurgery
      operations (103 artery, 125 vein anastomoses) performed in 96 patients with
      respect to size discrepancy. These operations included free flap transfer (n=67),
      replantation (n=23), revascularization (n=6), and toe-to-hand transplantation
      (n=3). Size discrepancy was defined as the inequality of vessel diameters at a
      ratio of 1:1.5 or greater. RESULTS: Size discrepancy was found in 32.5% (n=74) of
      228 anastomoses, the most frequent being in vein anastomoses performed during
      free flap transfers. Simple discrepancies were dealt with by dilatation with the
      use of a jeweller's forceps in 14 anastomoses. In nine discrepancies exceeding
      1:1.5, the oblique cut, fish mouth cut, and sleeve techniques were employed in
      four, three, and two anastomoses, respectively. End-to-side anastomosis was used
      in six patients in whom free flap transfer was carried out for extremity defects.
      The remaining 45 anastomoses were performed using a modification of the Xiu and
      Song's method. Venous grafts were used because of tension of the anastomosis and
      insufficient vessel lengths in three, eight, and three patients who underwent
      replantation, free flap transfer, and revascularization, respectively.
      CONCLUSION: An appreciation of various techniques is essential to avoid
      discrepancy-related problems both during and following microvascular surgery.

PMID- 14963395
TI  - [Comparison of temperature increments in bone cavities induced by
      methylmethacrylate and heated saline solution].
AB  - OBJECTIVES: We administered saline solution at 70 degrees C and
      methylmethacrylate to varying volumes of bone cavities and compared temperature
      changes produced in bone regions at varying distances to the cavity wall.
      METHODS: We created varying sizes of cavities in the femoral heads of 20 human
      cadavers (6, 10, 12, and 20 cubic centimeters) and in the knee region of a human
      cadaver (6, 10, 12, 20, 30, and 40 cubic centimeters). Initially, saline solution
      at 70 degrees C was administered to all the cavities for 15 minutes by a pulse
      irrigation method, during which temperature changes induced within the bone
      cavity and at specific distances (1, 2, 3, and 10 mm) to the cavity wall were
      recorded. The bone temperatures were allowed to return to initial values;
      thereafter, cement was applied and temperature changes at the same distances to
      the cavity wall, in the cement center, and on the cement surface were recorded.
      RESULTS: Cement volumes up to 40 cubic centimeters applied to the bone cavities
      did not produce temperature increments that are reported to be adequate to induce
      necrosis in the cavity wall. It was thought that cement-induced necrosis in the
      bone-cement interface was not related to heat, but to other effects exerted by
      cement application. Compared to cement-induced temperature changes, saline
      solution at 70 degrees C was always associated with higher temperature increments
      in the cavity wall. CONCLUSION: Due to its simple applicability at desired
      temperatures and for any lengths of time, heated saline solution seems to have
      credentials to be incorporated into local adjuvants that are utilized to
      eliminate tumoral contamination in the cavity wall following curettage for local
      aggressive tumors.

PMID- 14963396
TI  - [Evaluation of biomechanical rigidity of K-wire configurations in transverse
      osteotomies: a comparison of four-point bending test results].
AB  - OBJECTIVES: Four-point bending test was performed in transverse osteotomies of
      chicken humerus in order to assess biomechanical rigidity of fixation techniques
      that are commonly used in transverse unstable fractures of the tubular bones of
      the hand. METHODS: Thirty chicken humeral bones were transversely osteotomized
      and then randomly assigned to six fixation groups equal in number. Osteotomized
      bones were fixed with the use of two crossed (2 groups) or intramedullary (2
      groups) K-wires; in the remaining two groups, crossed K-wires were used in
      combination with tension band wiring. The sizes of the crossed and intramedullary
      K-wires were 0.035-inch and 0.045-inch in paired groups, respectively.
      Biomechanical rigidity was measured by four-point bending test on an Instron
      testing machine. RESULTS: The most rigid configuration was obtained with 0.045
      inch K-wires, followed by 0.035-inch K-wires used in combination with tension
      band wiring. These techniques provided significantly increased rigid fixations
      than those obtained by non-supplemented crossed and intramedullary K-wire
      fixations. CONCLUSION: In the transverse fractures of the tubular bones of the
      hand, dorsally applied tension band wiring around two crossed K-wires provides
      adequate rigidity that allows early active motion in the postoperative period.

PMID- 14963397
TI  - [The effects of early intermittent high-dose estrogen treatment on bone structure
      of ovariectomized rats].
AB  - OBJECTIVES: The effects of various estrogen replacement protocols to prevent bone
      loss following ovariectomy have been the subject of many studies in rats. This
      study was designed to determine the effects of early intermittent high-dose
      estrogen replacement therapy, which has hitherto not been studied, on bone
      structure of ovariectomized rats. METHODS: Bilateral ovariectomies were performed
      in 20 female mature non-pregnant Wistar rats. All the animals were randomly
      assigned to two groups to receive either subcutaneous 17 beta-estradiol (25
      mg/kg) or only sesame oil on days 15 and 22 after ovariectomy. Fourteen days
      after the last injection, the rats were sacrificed and proximal femurs were
      removed for both light and electron microscopic analyses. RESULTS: In the light
      microscopic analysis, control femurs exhibited a marked destruction in the
      structure of the cancellous bone, whereas estradiol-treated rats had almost
      normal cancellous bone. Ultrastructural analysis showed degeneration and
      increased turnover in bone cells of the control femurs, whereas the bone cells
      and the bone matrix appeared almost normal in the treatment group. A
      statistically significant increase in serum estrogen levels was found in
      estradiol-treated rats (580+/-124 pg/ml versus 62+/-16 pg/ml, p<0.001).
      CONCLUSION: Intermittent high-dose estrogen treatment prevents cancellous bone
      loss in the proximal femurs of ovariectomized rats through inhibition of bone
      turnover and results in significantly increased serum estrogen levels.

PMID- 14963398
TI  - [A case of ball-and-socket deformity of the ankle joint].
AB  - Ball-and-socket deformity of the ankle joint is a rare entity that is usually
      associated with inequality of leg length, fibular hypoplasia, coalition of the
      tarsal bones, and ray deficiency. This deformity was encountered in a nine-year
      old girl with a short right limb, cavovarus foot, partial fusion of the 4th and
      5th metatarsals, and talocalcaneonavicular coalition. No surgical intervention
      was necessary; the patient was recommended to wear a high-heeled shoe of 2.5 cm
      thickness to compensate for the difference in the leg length.

PMID- 14963399
TI  - [The efficacy of pulsed electromagnetic fields used alone in the treatment of
      femoral head osteonecrosis: a report of two cases].
AB  - Long-term radiologic and clinical results of pulsed electromagnetic fields (PEMF)
      are presented with illustration of two patients having Ficat-Arlet grade 2
      osteonecrosis of the femoral head. One patient (female, age 33 years) had
      bilateral involvement due to systemic steroid use, the other (male, age 39 years)
      had right-sided involvement of unknown etiology. Surgical treatment was ruled out
      because of aplastic anemia associated with significant thrombocyte deficiency in
      the first patient, while the other refused surgery. Pulsed electromagnetic fields
      were applied as the sole treatment modality in three hips for six months with a
      duration of 10 hours daily (at nights). At the end of 12-year- and five-year
      follow-ups, respectively, clinical improvement was observed in all hips, with no
      radiologic deterioration. It is concluded that application of PEMF stimulation
      alone may be an alternative treatment modality in patients in whom surgical
      treatment cannot be performed for femoral head osteonecrosis, in particular Ficat
      Arlet grade 1 and 2 disease.

PMID- 14963400
TI  - [Pelvic digit: a case report with reference to the differential diagnosis of
      pelvis abnormalities].
AB  - Pelvic digit was incidentally detected on plain pelvis radiography of a 44-year
      old male patient who presented with right-sided hip pain. Three-dimensional
      reconstruction of computed tomography scans provided a more clear illustration of
      the anatomy and localization of this anomaly. To avoid unnecessary investigation
      methods and treatment, this entity should be kept in mind when an atypical bone
      structure is noted around the pelvis

PMID- 14963401
TI  - A simple geometrical pattern for the branching distribution of the bronchial
      tree, useful to estimate optimality departures.
AB  - The design of the bronchial tree has largely been proposed as a model of optimal
      design from a physical-functional perspective. However, the distributive function
      of the airway may be more related to a geometrical than a physical problem. The
      bronchial tree must distribute a three dimensional volume of inspired air on a
      two dimensional alveolar surface, included in a limited volume. It is thus valid
      to ask whether an optimal bronchial tree from a physical perspective is also
      optimum from a geometrical point of view. In this paper we generate a simple
      geometric model for the branching pattern of the bronchial tree, deducing
      relationships that permit estimation of the departures from the geometrical
      optimum of each bifurcation. We also, for comparative purposes, estimate the
      departures from the physical optimum. From the geometrical assumptions: i) a
      symmetrical dichotomic fractal design, ii) with minimum volume and iii) maximum
      dispersion of the terminal points; and several simulations we suggest that the
      optimality is characterized by a bifurcation angle theta approximately 60 degrees
      and a length reduction scale gamma = (1/2)(1/3) = 0.7937. We propose distances
      from the physical and geometrical optimality defined as Euclidean distances from
      the expected optima. We show how the advanced relationships and the distances can
      be used to estimate departures from the optimality in bronchographs of four
      species. We found lower physical and geometrical departures in the distal zone
      than those of the proximal zones, as well as lower physical than geometrical
      departures from optimality.

PMID- 14963402
TI  - On Maxwell's demons and the origin of evolutionary variations: an internalist
      perspective.
AB  - This paper defends an internalist perspective of selection based on the
      hypothesis that considers living evolutionary units as Maxwell's demons (MD) or
      Zurek's Information Gathering and Using Systems (IGUS). Individuals are
      considered as IGUS that extract work by means of measuring and recording
      processes. Interactions or measurements convert uncertainty about the environment
      (Shannon's information, H) into internalized information in the form of a
      compressed record (Chaitin's algorithmic complexity, K). The requirements of the
      model and the limitations inherent to its formalization are discussed. This
      approach offers an alternative view to the causes of evolutionary variations
      which goes beyond the classical Lamarckian-Darwinian controversy. I argue that
      random variations only apply near-to-equilibrium at the time organisms have
      attained structural closure, and that a speed up of mutation rates that
      facilitates the production of directed variations occurs far-from-equilibrium due
      to organisms' openness to the surrounding conditions. However, real organisms are
      located somewhere between the above two cases and thus, operate at an
      intermediate stage where there is a maximum efficiency of H/K conversion. In
      consequence, IGUS keep their autonomy and evolving capacity by compromising
      between external circumstances and inner constraints. This compromise is made
      possible by closure regulation. Likewise, this model explains why nature has
      favored the selection of agents capable of selectively recording a partial
      description of their environment.

PMID- 14963403
TI  - The fractal dimension as a measure of the quality of habitats.
AB  - Habitat fragmentation produces isolated patches characterized by increased edge
      effects from an originally continuous habitat. The shapes of these patches often
      show a high degree of irregularity: their shapes deviate significantly from
      regular geometrical shapes such as rectangular and elliptical ones. In fractal
      theory, the geometry of patches created by a common landscape transformation
      process should be statistically similar, i.e. their fractal dimensions and their
      form factors should be equal. In this paper, we analyze 49 woodlot fragments (
      Pinus sylvestris L. ) in the Belgian Kempen region to study the direct
      relationship between a transformation process and the concomitant patch geometry.
      Although the fractal dimension of the woodlots is scattered (i.e. they are not
      statistically similar), the perimeter-area relation of the fragments is
      characterized by a single, 'dimension-like' exponent. This exponent suggests a
      certain shape homogeneity among the patches, which is confirmed by the absence of
      hierarchical levels associated with sharp increases of the fractal dimension at
      scale transitions. The interaction of different natural (soil factor, vegetation
      type) and anthropogenic (afforestation, urbanization) processes during patch
      development is assumed to have generated this feature. Comparison of the area and
      perimeter fractal dimension with an ecological index for habitat quality, the
      interior-to-edge ratio, shows that the fractal dimension is suitable for
      predicting interior habitat presence, which is more likely for patches with
      smooth perimeters and compact areas. The ratio of the area to the perimeter
      fractal dimension confirms this observation, with high values for high interior
      to-edge ratios, characteristic for regularly shaped patches.

PMID- 14963404
TI  - Failure of anti-tumor immunity in mammals--evolution of the hypothesis.
AB  - Observations on the morphological and functional similarity between embryonic or
      trophoblast tissues and tumors are very old. Over a period of time many
      investigators have created different hypotheses on the origin of cancerogenesis
      or tumor efficiency in relation to the host immune system. Some of these ideas
      have been rejected but many of them are still current. A presumption of the
      inefficiency of anti-tumor immunity in mammals due to the high similarity between
      trophoblast and embryonic cells to tumor cells is very real. The mechanisms for
      the escape of tumors from the immune response are very similar to the mechanisms
      for the escape of a fetoplacental unit from the maternal immune response. The
      similarity between these two mechanisms is so great that any randomness must be
      banished. At the same time, an incidence of malignant tumors and the types of
      more frequent tumors in non-mammalian vertebrates is significantly different to
      that in mammals. Lastly, the mechanisms of anti-tumor immunity in mammals are
      substantially different from the mechanisms of anti-tumor immunity in other
      classes of vertebrates. These facts indicate that the immune system of mammals
      during anti-tumor immune response is tricked by the similarity between tumor
      cells and trophoblast or other placental cells. From this aspect, our conclusion
      is that anti-tumor immunity failure in mammals can be defined as an
      immunoreproductive phenomenon, which is developed under the evolutionary pressure
      of autoimmunity and reproductive effectiveness.

PMID- 14963405
TI  - c-Myc: where death and division collide.
AB  - c-Myc is intimately involved in cell proliferation. However, inappropriate
      activation of c-Myc may also promote or sensitize cells to apoptosis. This is
      well established for several cell types and has been reinforced by a recent
      report in Cell Death and Differentiation by de Alboran and colleagues, who report
      that c-Myc-deficient B cells are resistant to several apoptotic stimuli,
      supporting a role for c-Myc in modulating B lymphocyte cell death. Here, we
      integrate these findings into the current picture of how c-Myc participates in
      cell death control.

PMID- 14963406
TI  - Low dose fractionated radiation potentiates the effects of taxotere in nude mice
      xenografts of squamous cell carcinoma of head and neck.
AB  - This study evaluated the combined effect of Low Dose Fractionated Radiation
      (LDFRT) and Taxotere (TXT) therapy on the growth of SCCHN (squamous cell
      carcinoma of head and neck; SQ-20B, a p53 mutant SCCHN cell line) tumors in a
      nude mouse model to exploit the increased hyper radiation sensitivity (HRS)
      phenomenon present in G(2)/M cell cycle phase when induced by low doses of
      radiation that was demonstrated in in vitro settings. Seventy-eight animals were
      randomized into one control group and 5 treatment groups (treatments were
      administered weekly for six weeks). Tumor regression was observed in all the
      groups, however, tumor regression was not significant in 2 Gy or TXT or 2 Gy plus
      TXT treated groups when compared to control group. The tumor regression was
      significant in both the LDFRT group (p < 0.0043) and LDFRT + TXT group (p <
      0.0006) when compared to other groups. A significantly prolonged tumor growth
      delay was observed in LDFRT group (p < 0.0081). Importantly, in combination of
      TXT and LDFRT, no tumor regrowth was observed in 12 out of 13 mice since LDFRT +
      TXT treatment caused a sustained regression of tumors for 9 weeks. Molecular
      analysis of resected tumor specimens demonstrated that Bax levels were elevated
      with concomitant increase in cytochrome c release to the cytosol of the treatment
      Group VI. These findings strongly suggest that LDFRT can be used in combination
      with TXT to potentiate the effects of drug on tumor regression through an
      apoptotic mode of death. Furthermore, the G(2)/M cell cycle arrest by TXT appears
      to be an important component of the enhanced apoptotic effect of TXT + LDFRT
      combined treatment.

PMID- 14963407
TI  - p21(WAF1/CIP1) at the switch between the anti-oncogenic and oncogenic faces of
      TGFbeta.

PMID- 14963408
TI  - The natural progression of microvasculature in primary tumor and lymph node
      metastases in a breast carcinoma model: relationship between microvessel density,
      vascular endothelial growth factor expression, and metastatic invasion.
AB  - The natural course of tumor microvascularity in rat MTLn3 mammary adenocarcinomas
      was studied. The relationship between microvessel density (MVD), vascular
      endothelial growth factor (VEGF) expression, and histopathology was compared in
      primary and metastatic axillary (ALN) and inguinal lymph node (ILN) tumors over 5
      6 tumor doublings. Excised tumors were examined for (i) MVD assessed by
      immunostaining with anti-CD31 antibody, (ii) VEGF expression assessed by
      immunostaining with anti-VEGF antibody, and (iii) histopathologic extent of
      metastatic lymph node invasion. MVD and VEGF scores rose asymptotically with
      increasing tumor weight in both primary and metastatic tumors. The MVD saturation
      level was significantly greater for primary tumors (MVD = 22) than for ALNs or
      ILNs (MVD = 14). Maximal VEGF score was not statistically different between the
      three kinds of tumors, however the rate of rise in VEGF expression was different.
      Near-maximal VEGF expression occurred early in tumor growth, preceding
      microvessel development. Both MVD and VEGF expression in lymph nodes were
      proportional to the pathology score characterizing increasing metastatic
      invasion. LNMs limited to the subcapsular sinus had the lowest MVD, indicating an
      ability to survive without significant vasculature. These findings underscore the
      differences in angiogenesis between primary tumors and LNMs and have implications
      for therapy of metastatic cancer.

PMID- 14963409
TI  - A field guide to the Mps1 family of protein kinases.
AB  - Cell cycle events must be faithfully executed and properly integrated to ensure
      genetic stability. The Mps1 family of protein kinases has recently emerged as a
      critical regulator of genetic stability, because they regulate several processes
      central to mitotic fidelity. The spindle checkpoint monitors alignment of mitotic
      chromosomes, and centrosomes control cell cycle entry, mitotic spindle assembly,
      and cytokinesis. Several studies have shown that vertebrate orthologues of
      budding yeast Mps1p regulate the spindle checkpoint. More recently it has been
      demonstrated that human Mps1 is also required for centrosome duplication, normal
      mitotic progression, and cytokinesis.

PMID- 14963410
TI  - Colon cancer metastasis: is E2F-1 a driving force?

PMID- 14963412
TI  - ZBP-89-induced apoptosis is p53-independent and requires JNK.
AB  - ZBP-89 induces apoptosis in human gastrointestinal cancer cells through a p53
      independent mechanism. To understand the apoptotic pathway regulated by ZBP-89,
      we identified downstream signal transduction targets. Ectopic expression of ZBP
      89 induced apoptosis through the mitochondrial pathway and was accompanied by
      activation of all three MAP kinase subfamilies: JNK1/2, ERK1/2 and p38 MAP
      kinase. ZBP-89-induced apoptosis was markedly enhanced by ERK inhibition with
      U0126. In contrast, inhibiting JNK with a JNK1-specific peptide inhibitor or
      dominant-negative JNK2 expression abrogated ZBP-89-mediated apoptosis. The p38
      inhibitor SB202190 had no effect on ZBP-89-induced cell death. Protein
      dephosphorylation assays revealed that ZBP-89 activates JNK via repression of JNK
      dephosphorylation. Oligonucleotide microarray analyses revealed that ectopic
      expression of ZBP-89 downregulated expression of the dual-specificity phosphatase
      MKP6. Overexpression of MKP6 blocked ZBP-89-induced JNK phosphorylation and PARP
      cleavage. In addition, ectopic expression of ZBP-89 repressed Bcl-xL and Mcl-1
      expression, but had no effect on Bcl-2. Silencing ZBP-89 with small interfering
      RNA enhanced both Bcl-xL and Mcl-1 expression. Taken together, ZBP-89-mediated
      apoptosis occurs via a p53-independent mechanism that requires JNK activation.

PMID- 14963413
TI  - Apoptosis induced by staurosporine in ECV304 cells requires cell shrinkage and
      upregulation of Cl- conductance.
AB  - We show that dysregulation of the Cl- homeostasis mediates the staurosporine
      induced apoptotic cell death in human ECV304 cells. A pronounced apoptotic volume
      decrease (AVD), and an increase in plasma membrane Cl- conductance were early (<1
      h) events following staurosporine challenge. Both processes were involved in
      apoptotic death, as demonstrated by the observation that the Cl- channel blocker
      phloretin inhibited both the staurosporine-evoked Cl- current and AVD, and
      preserved cell viability. Prolonged incubation (>2 h) with staurosporine caused a
      decrease in intracellular pH, which, however, was not required for the
      progression of the apoptotic process, because inhibitors of proton extrusion
      pathways, which lowered cytoplasmic pH, failed to inhibit both caspase-3
      activation and DNA laddering. Moreover, clamping the cytosolic pH to an alkaline
      value did not prevent the apoptotic cell death. Collectively, these data
      demonstrate that staurosporine-mediated apoptosis of ECV304 cells is caused by
      the upregulation of Cl- channel activity and subsequent AVD, but is independent
      of intracellular acidification.

PMID- 14963414
TI  - Perspectives.

PMID- 14963415
TI  - Tristan da Cunha.

PMID- 14963416
TI  - GDC fees for the retired.

PMID- 14963418
TI  - Consensus on training.

PMID- 14963419
TI  - GDC fees for the retired.

PMID- 14963420
TI  - GDC fees for the retired.

PMID- 14963430
TI  - Strap him down or knock him out: Is conscious sedation with restraint an
      alternative to general anaesthesia?
AB  - When confronting a defiant or pre-co-operative young patient with extensive
      dental decay the dentist must decide between treatment under conscious sedation
      with passive restraint or general anaesthesia. Although some practitioners prefer
      to attempt and exhaust sedative techniques in most cases and use general
      anaesthesia as a last resort, many others do not mandate that alternate
      approaches first be attempted before treating under general anaesthesia and
      routinely recommend it as their first choice. What are the considerations
      involved in this decision-making process? Should the use of conscious sedation
      with restraint be revisited and perhaps even be considered the preferred method?
      What is the role of the dentist in the decision-making process? The purpose of
      this opinion-based paper is to present to the UK dentist a dilemma that
      paediatric dentists face in the US and in other countries as well and allow the
      reader to establish an opinion.

PMID- 14963431
TI  - A UK perspective.

PMID- 14963432
TI  - A commentary on the legal issues.

PMID- 14963433
TI  - Orthodontics. Part 7: Fact and fantasy in orthodontics.
AB  - Clinical research has previously lacked good methodology and much opinion was
      based on anecdote which is widely regarded as the weakest form of clinical
      evidence. There are few randomised control trials in orthodontics which support
      or refute areas of dogma. The number of randomised control trials is increasing
      significantly. There is currently however no good evidence that orthodontics
      causes or cures temporomandibular joint dysfunction, that appropriate extractions
      in orthodontics ruin patients' profiles, or that the orthodontist is able to
      significantly influence facial growth with appliances.

PMID- 14963441
TI  - Total viable counts, ATP, and endotoxin levels as potential markers of microbial
      contamination of dental unit water systems.
AB  - OBJECTIVES: To determine if either ATP or endotoxin concentrations in water
      supplied by dental unit water systems (DUWS) correlated with total viable counts
      (TVC), and therefore could be used as a rapid, chairside measure of levels of
      microbial contamination. DESIGN: A prospective trial. METHOD: Fifty-seven water
      samples were taken from the 'triple spray', air rotor and source water supplies
      from 25 dental units in eight practices. The samples were assayed for endotoxin
      concentration, total ATP and TVC. A pilot study was performed to assess the
      relationship between TVC and total cell counts, as determined by flow cytometry.
      RESULTS: ATP concentrations ranged from 22 to 958 relative light units (RLU) and
      free endotoxin ranged from 25 to 600 EU ml(-1). TVC varied from not detected to
      2.16 x 10(4) CFU ml(-1). The ATP method proved to be a simple and rapid method
      that could be used at the chairside. However, there was no correlation between
      ATP or endotoxin concentrations and TVC in DUWS. TVC generally underestimated the
      total cell count by 50 to 500 fold. CONCLUSION: Half of the water samples from
      DUWS exceeded recommended levels of TVC. However, ATP and endotoxin
      concentrations in DUWS water samples did not correlate with these TVC data and
      therefore could not be recommended as an alternative assay to TVC for measuring
      bacterial contamination or for monitoring water treatment efficacy.

PMID- 14963442
TI  - Dentists interacting and working with female dental nurses: a qualitative
      investigation of gender differences in primary dental care.
AB  - OBJECTIVES: To investigate if women compared with men dentists experience
      deferential treatment from their female nurses, what workplace strategies women
      use to manage chair-side assistance and to examine if these were country related.
      METHOD: A convenience sample of 22 male and female dentists of different ages
      working in general dental practice in The Netherlands and Northern Ireland
      participated. The sample framework was determined by saturation of the concepts.
      All informants were interviewed in a clinical setting. The data was subjected to
      rigorous line by line coding in order to identify clusters of codes, themes and
      concepts. RESULTS: Three themes were identified. These were: experiencing
      deferential nursing assistance; adopting 'friendly-like' working strategies and
      adopting business-like, hierarchical working strategies. Gender differences were
      shown for each of the themes. Women rather than men made friends with their
      nurses and attempted to reduce status inequalities. This led to workplace
      strategy inconsistencies. This suggested that it was not the type of strategy
      adopted but the inconsistency with which it was implemented that caused
      difficulties between younger women dentists and their nurses. CONCLUSIONS:
      Training dental students and young graduates how to interact appropriately in the
      clinical situation and to appreciate the nurses' work status will assist in
      improving working relationships.

PMID- 14963443
TI  - An investigation of post-operative morbidity following iliac crest graft
      harvesting.
AB  - OBJECTIVE: A study which examined the morbidity experienced by patients who
      underwent iliac crest bone graft procedures. DESIGN: A post-operative
      questionnaire was forwarded to patients who underwent iliac crest bone graft
      procedures at a single centre. SUBJECTS: One hundred and fourteen patients
      underwent iliac crest bone grafts for intra-oral augmentation. RESULTS: Ninety
      eight patients (80%) returned post-operative questionnaires. Eighty of the 98
      (81.6%) patients suffered post-operative pain with 70% of patients being pain
      free after four weeks. However, 10% of patients experienced pain for more than 16
      weeks. Eighty-five (86.7%) patients were able to walk without any difficulties
      six weeks post-operatively. Gait disturbance was not related with age, however
      there was a significant association between pain and disturbance of gait (P<
      0.001). Twenty two patients required the use of a walking stick and the use of
      such aids varied from 0.5 to 26 weeks. Women used walking aids for longer periods
      than men (P< 0.05). Twenty five patients had altered sensation with about half of
      them experiencing altered sensation in the distribution of the lateral femoral
      cutaneous nerve. Other morbidities included deformity at the hip site (2.4%),
      haematoma (2.4%), infection (3.2%), stress fracture (4.1%) and meralgia
      paraesthetica in one patient. Despite the above morbidities, 82 patients were
      willing to undergo the same procedure again and 89 patients would recommend the
      procedure to their relatives and friends. CONCLUSION: This study demonstrates
      considerable morbidity following anterior iliac crest bone harvest for intra-oral
      augmentation. Clinicians referring patients for such bone graft procedures must
      be aware of the above morbidities so that any patients referred for such
      procedures are fully informed.

PMID- 14963456
TI  - The increasing demand and necessity for a team approach.
AB  - The role of professionals complementary to dentistry (PCDs) has changed radically
      in recent times and further changes are likely in the foreseeable future. The
      modernisation of dentistry throughout the UK dictates that the existing workforce
      takes into account the substantial contribution which can be made by PCDs in
      addressing the unacceptable levels of disease which exist in many parts of the
      country.

PMID- 14963460
TI  - Survivin expression in ovarian carcinoma: correlation with apoptotic markers and
      prognosis.

PMID- 14963464
TI  - A comparative, crossover study of the efficacy and safety of sildenafil and
      apomorphine in men with evidence of arteriogenic erectile dysfunction.
AB  - The aim of the study was to establish and compare the efficacy and safety of
      sildenafil and apomorphine in men with arteriogenic erectile dysfunction (ED). In
      all, 43 men with ED and postinjection max penile systolic velocity <25 cm/s in
      repeated Doppler ultrasonography were included. Of these, 24 men started on
      apomorphine 2 mg and 19 on sildenafil 50 mg, the doses titrated up to 3 and 100
      mg according to effectiveness and tolerability. Safety was evaluated according to
      adverse events (AEs) and patient withdrawal. Efficacy was the percentage of
      attempts resulting in erections firm enough for intercourse, based on event log
      data. The incidence of AEs with apomorphine 3 mg was higher than with sildenafil
      100 mg. Two men on apomorphine 3 mg discontinued treatment due to AEs. The
      overall success rate of sildenafil was 63.7% compared to 32.1% of apomorphine
      (Pearson chi(2), P<0.01). Of all men, 25 (58.1%) responded to sildenafil 50 mg
      without the need for dose increase, while only one responded to apomorphine 2 mg.
      The response to sildenafil 50 mg was age related (analysis of variance, p=0.04).
      Satisfaction was reported by 76.75 and 13.95% of patients for sildenafil and
      apomorphine, respectively, but 20.9% were not satisfied with any of the two
      drugs. In conclusion, this study provides clear evidence that sildenafil, even at
      50 mg dose, is more effective than apomorphine 3 mg in men with arteriogenic ED.
      The fact that one out of five patients is not satisfied with the above-studied
      drugs shows that new oral agents need to be evaluated for the treatment of this
      disorder.

PMID- 14963465
TI  - Sildenafil citrate vs intracavernous alprostadil for patients with arteriogenic
      erectile dysfunction: a randomised placebo controlled study.
AB  - We compared the effectiveness of sildenafil citrate and alprostadil in improving
      arterial penile inflow (peak systolic velocity (PSV)) and penile rigidity in 55
      patients with erectile dysfunction caused by atherosclerosis. A total of 35
      patients with pure vasculogenic impotency were randomly assigned to alprostadil
      (Av group; n=11), sildenafil (Sv group; n=12), or placebo (P group; n=12), and 20
      patients with nonvasculogenic impotency were randomly assigned to alprostadil (A
      group; n=10) or Sildenafil (S group; n=10): Av and A used alprostadil injection
      (capable of giving a full erection) once a week for 1 month, Sv and S took daily
      oral sildenafil (25 mg) for 1 month, and P took daily oral placebo for one month.
      The PSV was measured with Duplex sonography and penile rigidity was assessed
      using the IIEF-15 questionnaire, both of which were administered before and after
      treatment. Although both treatments improved penile rigidity, they increased PSV
      only in the Av and Sv groups. Our results suggest that alprostadil and oral
      therapy should be the starting therapy in men with vasculogenic impotency,
      whereas alprostadil should be avoided as the first-line approach in men with
      nonvasculogenic impotency.

PMID- 14963466
TI  - Characteristics of erectile dysfunction in Saudi patients.
AB  - We investigated the characteristics of erectile dysfunction (ED) in ambulatory
      Saudi patients. A total of 680 male patients were assessed for ED using IIEF.
      Patients were also interviewed for sociodemographic data, medical history and
      risk factors for ED. Assessment for penile vasculature using color Doppler
      ultrasonography and rigidometer was performed. In all, 21.4% of the patients with
      severe ED were <50 y and 78.6% of them were > or =50 y (P<0.001). Of the
      patients, 20% had psychogenic, while 80% had organic causes of ED. Of the
      patients, 10% had mild, 39.3% had moderate and 50.7% had severe ED. There was a
      significant association between increasing severity of ED and the presence of
      diabetes, hypertension, dyslipidemia, smoking, increased BMI, increased values of
      EDV, decreased values of PSV, RI and rigidometer (P<0.001 for each). Moderate to
      severe ED is common among Saudi patients. This study provides a quantitative
      estimate of the characteristics of ED in ambulatory Saudi patients.

PMID- 14963467
TI  - Effect of combination endothelial nitric oxide synthase gene therapy and
      sildenafil on erectile function in diabetic rats.
AB  - Erectile dysfunction associated with diabetes mellitus is caused in part by
      disordered endothelial smooth muscle relaxation, neuropathy, and a decrease in
      cavernosal nitric oxide synthase (NOS) activity. The purpose of this study was to
      determine whether a combination of sildenafil and adenoviral gene transfer of
      endothelial NOS (eNOS) could enhance the erectile response in diabetic rats. Five
      groups of animals were utilized: (1) age-matched control rats, (2) streptozotocin
      (STZ)-induced diabetic rats (60 mg/kg i.p.), (3) STZ-rats + sildenafil (2 mg/kg
      i.v.), (4) STZ-rats transfected with AdCMVbetagal or AdCMVeNOS, and (5) STZ-rats
      transfected with AdCMVeNOS +sildenafil (2 mg/kg i.v.). At 2 months after i.p.
      injection of STZ, groups 4 and 5 were transfected with the adenoviruses and 1-2
      days after transfection, all animals underwent cavernosal nerve stimulation (CNS)
      to assess erectile function. Cyclic 3',5'-guanosine monophosphate (cGMP) levels
      were assessed in the cavernosal tissue. STZ-diabetic rats had a significant
      decrease in erectile function as determined by the peak intracavernosal pressure
      (ICP) and total ICP (area under the erectile curve; AUC) after CNS when compared
      to control rats. STZ-diabetic rats+AdCMVeNOS had a peak ICP and AUC, which were
      similar to control animals. STZ-diabetic rats administered sildenafil
      demonstrated a significant increase in peak ICP at the 5 and 7.5 V settings,
      while the AUC was significantly increased at all voltage (V) settings. The
      increase in both ICP and AUC of STZ-diabetic rats transfected with AdCMVeNOS at
      all V settings was greater than STZ-diabetic rats transfected with AdCMVbetagal.
      STZ-diabetic rats transfected with AdCMVeNOS and administered sildenafil had a
      significant increase in total ICP that was greater than eNOS gene therapy alone.
      Cavernosal cGMP levels were significantly decreased in STZ-diabetic rats, but
      were increased after transfection with AdCMVeNOS to values greater than control
      animals. In conclusion, overexpression of eNOS and cGMP in combination with
      sildenafil significantly increased both the peak ICP and total ICP to CNS in the
      STZ-diabetic rat, which was similar to the response observed in control rats.
      Moreover, the total erectile response was greater in STZ-diabetic rats receiving
      eNOS gene therapy plus sildenafil than STZ-rats receiving sildenafil or eNOS gene
      therapy alone.

PMID- 14963468
TI  - Development and validation of the Self-Esteem And Relationship (SEAR)
      questionnaire in erectile dysfunction.
AB  - Development and validation of a patient-reported measure of psychosocial
      variables in men with erectile dysfunction (ED) is described. Literature review,
      focus groups, and medical specialists identified 86 potential items. Redundant,
      ambiguous, or low item-to-total correlation items were removed. Data from 98 men
      reporting diagnosed ED and 94 controls assisted in final item selection and
      psychometric evaluation. Treatment responsiveness was evaluated in 93 men with ED
      in a 10-week open-label trial of sildenafil citrate (Viagra). The 14 chosen items
      resolved into two domains: Sexual Relationship (eight items) and Confidence (six
      items), the latter comprising Self-Esteem (four items) and Overall Relationship
      (two items) subscales. The resulting Self-Esteem And Relationship (SEAR)
      questionnaire demonstrated validity and reliability. The intervention study
      demonstrated responsiveness to beneficial treatment with significant improvement
      in scores (P=0.0001). The SEAR questionnaire possesses strong psychometric
      properties that support its validity and reliability for measuring sexual
      relationship, confidence, and particularly self-esteem.

PMID- 14963469
TI  - Impairment of shear-stress-mediated vasodilation of cavernous arteries in
      erectile dysfunction.
AB  - Penile NO release test (PNORT) has been designed to try to evaluate clinically
      the penile endothelial function (PEF). The shear-stress flow-mediated
      vasodilation (FMD) of the cavernous arteries is evaluated in two groups of
      patients with neurogenic (n=23) and vasculogenic (n=23) erectile dysfunction (ED)
      by measuring their percent of increase after a 5 min occlusion of the flow. Both
      groups show an important FMD decrease (17.78+/-11.78 and 17.82+/-13%) as compared
      to the age-matched control group (n=12) (65.14+/-30.5%, P<0.001). In the
      vasculogenic and control groups, mean FMD is lower in patients with one or more
      arterial risk factors(41 vs 67%, P=0.025), and show a positive correlation with
      the plasmatic levels of bioavailable testosterone (r=0.37, P=0.03) and of DHEA-S
      (r=0.46, P=0.014). Patients achieving full erection at pharmacological test with
      visual sexual stimulation have a higher FMD (43.8+/-38%) than those who did not
      (18.52+/-14.37%, P=0.008). We confirm clinically that PEF is strongly impaired in
      organic ED linked to neurological, vascular and endocrine factors.

PMID- 14963470
TI  - Effects of ovariectomy and steroid hormones on vaginal smooth muscle
      contractility.
AB  - The role of steroid hormones in regulating vaginal smooth muscle contractility
      was investigated. Rabbits were kept intact or ovariectomized. After 2 weeks,
      animals were continuously infused with vehicle or supraphysiological levels of
      testosterone (100 microg/day), or estradiol (200 microg/day), for an additional 2
      weeks. The distal vaginal tissue was used to assess contractility in organ baths
      and changes in tissue structure were assessed by histology. Ovariectomized
      animals infused with vehicle exhibited significant atrophy of the muscularis and
      decreased epithelial height, resulting in thinning of the vaginal wall. Estradiol
      infusion increased epithelial height, comparable to that of intact animals, but
      only partially restored the muscularis layer. In contrast, testosterone infusion
      completely restored the muscularis layer, but only partially restored the
      epithelial height. In vaginal tissue strips contracted with norepinephrine and
      treated with bretylium, electrical field stimulation (EFS) caused frequency
      dependent relaxation that was slightly attenuated with vehicle, significantly
      inhibited with estradiol and significantly enhanced with testosterone. VIP
      induced relaxation was slightly attenuated in tissues from vehicle and estradiol
      infused groups, but was enhanced in tissues from testosterone-infused animals.
      Contraction elicited by EFS or exogenous norepinephrine was not significantly
      altered with ovariectomy or steroid hormone infusion when data were normalized to
      potassium contraction. However, the tissue from testosterone-infused animals
      developed significantly greater contractile force to norepinephrine. These
      observations suggest that steroid hormones may be important regulators of vaginal
      tissue structure and contractility.

PMID- 14963471
TI  - Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic
      properties and pharmacodynamic effects of intranasal PT-141, a melanocortin
      receptor agonist, in healthy males and patients with mild-to-moderate erectile
      dysfunction.
AB  - PT-141, a cyclic heptapeptide melanocortin analog, was evaluated following
      intranasal administration in healthy male subjects and in Viagra-responsive
      erectile dysfunction (ED) patients. Erectile response was assessed by RigiScan
      trade mark in healthy subjects without visual sexual stimulation (VSS) and in
      Viagra-responsive ED patients with VSS. In healthy subjects, mean C(max) and
      AUC((0-t)) increased in a dose-dependent manner. Median T(max) was 0.50 h and
      mean t(1/2) ranged from 1.85 to 2.09 h. In both studies, an erectile response
      induced by PT-141 administration was statistically significant, compared to
      placebo, at doses greater than 7 mg, with the onset of the first erection
      occurring in approximately 30 min. PT-141 was safely administered and well
      tolerated in both studies. A maximum-tolerated dose was not identified. Flushing
      and nausea were the most common adverse events reported in both studies and no
      clinically significant changes in vital signs, laboratory tests, ECGs, or
      physical exams were observed. Based upon its erectogenic potential and
      tolerability profile, PT-141 is a promising candidate for further evaluation as a
      treatment for male ED.

PMID- 14963472
TI  - The role of general practitioners in the management of erectile dysfunction-a
      qualitative study.
AB  - The objective of this study was to explore the roles and perceptions of general
      practitioners (GPs) in the management of erectile dysfunction (ED). This
      qualitative study used focus group discussions and in-depth interviews. This
      study was conducted based on 28 GPs from an urban area in Malaysia who had
      managed patients with ED and prescribed anti-ED drugs. Main outcome measures
      included the roles of GPs in managing patients with ED (active or passive),
      perceptions regarding ED and the treatment, and factors influencing their
      decision to prescribe. Majority of the GPs assumed a passive role when managing
      patients with ED. This was partly due to their perception of the disease being
      nonserious. Some also perceived ED as mainly psychological in nature. The anti-ED
      drugs were often viewed as a lifestyle drug with potentially serious side
      effects. The fear of being perceived by patients as 'pushing' for the drug and
      being blamed if the patients were to develop serious side effects also hampered
      the management of this disease. GPs who participated in this study remained
      passive in identifying and treating patients with ED and this was attributed to
      their perception of the disease, drug treatment and patient's background.

PMID- 14963473
TI  - Rechallenge prior sildenafil nonresponders.
AB  - To assess inappropriate use as a cause of sildenafil (Viagra ) failure and the
      feasibility of successfully rechallenging nonresponding patients, a total of 60
      consecutive erectile dysfunction (ED) patients who first presented to our
      hospital and claimed poor response to sildenafil were enrolled into the study.
      The International Index of Erectile Function-5 (IIEF-5) was used to evaluate
      their baseline ED status and a self-administered sildenafil-use questionnaire
      composed of nine questions (SUQ-9) to assess how they had used sildenafil. A
      total of 44 subjects consent to rechallenge with sildenafil and were given
      thorough instruction based on individual answers to SUQ-9 and four doses of
      sildenafil 100 mg. After a 4-week follow-up, end point efficacy of rechallenge
      was evaluated using the IIEF-5 and the global assessment question (GAQ), 'After
      the treatment, did you have successful sexual intercourse?' Of the 60 subjects,
      44 (77.3%) had one or more areas of major suboptimal use of sildenafil: 18
      (30.0%) did not know that sexual stimulation was necessary for sildenafil to
      work, 36 (60.0%) attempted to use sildenafil less than four times, and 27 (45.0%)
      took a maximal dose less than 100 mg. Of the 44 patients undergoing sildenafil
      rechallenge, 34 (77.3%) completed the follow-up, while seven (15.9%) received
      only GAQ assessment by telephone interview and three (6.8%) were lost to follow
      up. The total follow-up rate was 93.2% (41/44). Based on answers to the GAQ, the
      response rate to rechallenge was 58.5% (24/41). The mean improvement in the IIEF
      5 score was 8.4+/-5.5 in responders (P <0.05). With individualized thorough
      instruction based on answers to SUQ-9 and scheduled follow-up, a high success
      rate was achieved by rechallenge with sildenafil in prior failures. The efficacy
      of sildenafil could be improved to a great extent by adequate education of
      patients and continuing medical education given to primary-care physicians.

PMID- 14963474
TI  - Prevalence of sexual dysfunctions in Argentina.
AB  - The objective of this study consisted in assessing the prevalence of erectile
      dysfunction (ED) and other sexual dysfunctions in a group of men who attended a
      prostate awareness week campaign. In total, 2715 men attended to 'Semana de la
      Prostata 2001' campaign and received an additional questionnaire on sexual
      health. The prevalence of ED, desire and ejaculatory disorders was of 41.7, 33.8
      and 49.3%, respectively; however, not all of them lived these difficulties as a
      real sexual problem because only 918 men (37.8%) acknowledged having 'any sexual
      difficulty'. Only 13.7% of the attendees consulted a physician for this reason in
      the past. This first Argentinean study proves the high prevalence of sexual
      dysfunctions in our population.

PMID- 14963475
TI  - Feline penile erection induced by topical glans penis application of combination
      alprostadil and SEPA (Topiglan).
AB  - The objective of this study was to evaluate the efficacy of topically applied
      prostaglandin E1 (PGE(1))+5% SEPA (soft enhancement of percutaneous absorption)
      on the glans penis in a feline erection model. Erectile response after glans
      penis administration of PGE(1)+5% SEPA cream (Topiglan, MacroChem Co., Lexington,
      MA, USA) was compared to the erectile response after intracavernosal
      administration of the triple-drug combination (1.65 mg papaverine, 25 microg
      phentolamine, and 0.5 microg PGE(1)). The placebo cream and increasing
      concentrations (0.25%, 2.5 mg/ml; 0.5%, 5 mg/ml; and 1%, 10 mg/ml) of PGE(1)+5%
      SEPA were applied in a total volume of 0.1 ml via a plastic needle-less syringe.
      The control triple-drug combination was administrated intracavernosally via a 30
      gauge needle at the completion of each experiment to serve as a control
      reference. With each application of placebo, PGE(1)+SEPA, and the triple-drug
      combination, changes in intracavernosal pressure and systemic blood pressure were
      continuously monitored. Topical application of PGE(1)+SEPA induced increases in
      intracavernosal pressure in a dose-dependent manner, with minimal effects on
      systemic blood pressure. The increases obtained with 1% PGE(1) Topiglan cream
      were similar to the intracavernosal pressure values elicited by the standard
      intracavernosal triple-drug combination. These data demonstrate that topical
      glans penis application of PGE(1)+SEPA can induce an erectile response in cats
      with minimal systemic adverse effects. Oral pharmacological agents are the first
      line treatment for male ED. Studies investigating the effectiveness of
      noninvasive modalities such as topical therapy should continue, because these
      agents have the potential to avoid the systemic effects commonly seen with oral
      therapies. Additionally, topical therapy may also benefit patients who are
      unresponsive to oral agents or have explicit contraindications. Topical PGE(1)
      application to the glans penis may become an important treatment option in
      selected patients suffering from erectile dysfunction.

PMID- 14963476
TI  - Natural remedies for impotence in medieval Persia.
AB  - Man's preoccupation with potency, or the lack thereof, has been present through
      the ages. Several documents still exist from which the clinical approaches of
      erectile dysfunction (ED) in medieval Persia can be ascertained. The medieval
      physicians described definitions and apparent causes of ED. They also noted
      hygienic and dietary rules as well as long lists of natural substances used in
      the treatment of ED. Many of the approaches of practitioners in medieval Persia
      are accurate and accepted even today; however, still more of them could be of use
      to modern medicine. The present review provides an overview of the knowledge of
      ED at the time.

PMID- 14963477
TI  - Gabapentin in the management of the recurrent, refractory, idiopathic priapism.
AB  - Recurrent idiopathic priapism is a difficult problem to treat and a true
      emergency for the physicians, and often even invasive therapeutic interventions
      fail. We recently managed three men with refractory idiopathic priapism with oral
      gabapentin. They responded to treatment within 48 h. Two men continue not to
      experience prolonged erections while treated with lower doses of gabapentin for
      16 and 24 months, respectively. The third, after a successful treatment for 6
      months, stopped gabapentin and priapism recurred. He responded to treatment again
      and continues to be free of episodes for 9 months. Gabapentin may be a safe
      alternative for the management of refractory idiopathic priapism.

PMID- 14963478
TI  - Cholinergic facilitation of erection and ejaculation in spinal cord-transected
      rats.
AB  - Penile reflexes (PRs) were monitored in chronic spinal cord-transected rats by
      identifying them visually, and at the same time they were recorded as the
      electromyographic activity of bulbospongiosus muscles. Intraperitoneal injection
      of the agonist muscarine (10 microg) produced a facilitation of PRs. A decrease
      in the latency, an increase in the number of clusters and often an increase in
      the duration of cups were found after muscarine. In addition, 66% (six out of
      nine) of the animals ejaculated after muscarine. These results suggest that
      cholinergic receptor stimulation may be involved in erectile and ejaculatory
      mechanisms mediated by the spinal cord.

PMID- 14963479
TI  - Deep brain stimulation of the thalamus can influence penile erection.

PMID- 14963480
TI  - Treatment of testosterone-induced gynecomastia with the aromatase inhibitor,
      anastrozole.
AB  - Gynecomastia is an unusual side effect associated with testosterone replacement
      therapy (TRT) that has been traditionally treated with surgery, radiation, or
      discontinuation of testosterone supplementation. We report here our experience
      with two cases of gynecomastia in men undergoing TRT who were successfully
      treated with the aromatase inhibitor anastrozole.

PMID- 14963481
TI  - Mobile phone interference in the ophthalmology department.

PMID- 14963482
TI  - Effects of different degrees of cataract on the multifocal electroretinogram.
AB  - AIM: To study the effect of different degrees of nuclear cataract on the
      multifocal electroretinogram (mfERG). METHODS: mfERGs were recorded from 30
      elderly subjects with very mild, mild, or moderate nuclear cataracts using a
      VERIS System (version 4.1). The subjects were divided into three groups (10 in
      each group) according to their degree of nuclear cataracts as classified
      according to the Lens Opacities Classification System III (LOCS III). No subjects
      had any significant eye disease or degenerative changes except for cataracts. The
      mfERG responses were grouped into six concentric rings for analysis. Both the N1
      and P1 amplitudes and the latencies of N1 and P1 of first-order responses were
      used for analysis. RESULTS: Amplitudes of N1 and P1 from the central retina (14
      degrees) were significantly reduced in patients with mild or moderate cataract
      when compared with subjects with very mild cataract. However, there was no
      significant reduction of N1 and P1 amplitudes in the para-central retina (14-40
      degrees). There was no difference in the latencies of N1 and P1 in these three
      groups of subjects. CONCLUSIONS: The mfERG responses from the central retina
      (central 14 degrees) were affected by the severity of cataract, but responses
      from the paracentral retina (14-40 degrees) were not affected. This suggests that
      in interpreting the mfERG in subjects with mild or moderate cataract subjects
      some care should be taken as reduced amplitudes (N1 and P1) will be expected from
      the central retina.

PMID- 14963483
TI  - Outcomes in verteporfin photodynamic therapy for choroidal neovascularisation-
      'beyond the TAP study'.
AB  - AIMS: To report on the clinical efficacy of verteporfin photodynamic therapy
      (PDT) in the treatment of choroidal neovascularisation (CNV) in an NHS setting
      and to compare treatment rates and outcomes with those in the published
      literature. PATIENTS AND METHODS: Patients with a visual acuity of 6/60 or better
      Snellen equivalent and predominantly classic or classic/no occult CNV within 200
      microm of the centre of the fovea were enrolled and followed for a minimum of 12
      months. Assessment at baseline and all follow-up visits comprised refraction
      protocol logMAR visual acuity, contrast sensitivity, and stereoscopic fluorescein
      angiography. RESULTS: A total of 170 eyes of 159 patients were enrolled with CNV
      due to: 147 age-related macular degeneration (AMD) (90 classic/no occult, 21
      recurrent after confluent laser, 36 predominantly classic with occult), 10
      pathological myopia, and 13 others. Response to treatment (loss of < 15 letters)
      at 12 months was 73% overall, 76% in AMD, 70% in classic/no occult, and 89% in
      predominantly classic. The mean number of treatments in the first year was 2.7.
      Contrast sensitivity was unchanged. CONCLUSIONS: Verteporfin PDT delivered in a
      NHS setting can be at least as effective as and requires fewer treatments than
      reported in the literature.

PMID- 14963484
TI  - A comparison of three sub-Tenon's cannulae.
AB  - PURPOSE: To compare the quality of anaesthesia and complication rates between
      three sub-Tenon cannula of increasing length (anterior Greenbaum, mid Kumar
      Dodds, and posterior Steven's sub-Tenon's cannulae). METHODS: A total of 150
      patients undergoing cataract extraction were randomised to receive a sub-Tenon
      injection of 5 ml of 2% lidocaine with hyaluronidase with one of the three
      cannulae. The development of akinesia was assessed every 2 min over a 6-min
      period. Complications were also recorded. RESULTS: There was no difference in the
      onset of akinesia, with 46, 50, and 46 patients achieving adequate akinesia
      within 6 min for the anterior, mid, and posterior groups respectively (P>0.05).
      There was an increase in retained lid opening with anterior compared to mid and
      posterior cannulae (P=0.0001). There was significantly less retained lid closure
      with the posterior compared to the mid or anterior cannulae (P<00001). The mean
      (range, SD) scores for pain during injection were 0.4 (0-5, 0.83), 1.2 (0-9,
      1.96), and 1.1 (0-6, 1.19) for the anterior, mid, and posterior groups,
      respectively. These were not significantly different between the anterior and mid
      groups, or the mid and posterior groups (P>0.05), but there was significantly
      more pain on injection with the posterior compared to the anterior groups
      (P<0.01). All patients scored intraoperative pain as zero. There was
      significantly more chemosis in the anterior group (76%) compared to the mid (20%)
      and posterior (32%) groups (P<0.0001). There were significantly (P=0.0004) more
      conjunctival haemorrhages in the anterior group (56%) than the mid (20%) or
      posterior (20%) groups. CONCLUSIONS: We have shown that all three cannulae
      provide high-quality anaesthesia with minor differences in retained muscle
      activity, chemosis, and haemorrhage rates.

PMID- 14963485
TI  - Dilated cardiomyopathy caused by tissue-specific ablation of SC35 in the heart.
AB  - Many genetic diseases are caused by mutations in cis-acting splicing signals, but
      few are triggered by defective trans-acting splicing factors. Here we report that
      tissue-specific ablation of the splicing factor SC35 in the heart causes dilated
      cardiomyopathy (DCM). Although SC35 was deleted early in cardiogenesis by using
      the MLC-2v-Cre transgenic mouse, heart development appeared largely unaffected,
      with the DCM phenotype developing 3-5 weeks after birth and the mutant animals
      having a normal life span. This nonlethal phenotype allowed the identification of
      downregulated genes by microarray, one of which was the cardiac-specific
      ryanodine receptor 2. We showed that downregulation of this critical Ca2+ release
      channel preceded disease symptoms and that the mutant cardiomyocytes exhibited
      frequency-dependent excitation-contraction coupling defects. The implication of
      SC35 in heart disease agrees with a recently documented link of SC35 expression
      to heart failure and interference of splicing regulation during infection by
      myocarditis-causing viruses. These studies raise a new paradigm for the etiology
      of certain human heart diseases of genetic or environmental origin that may be
      triggered by dysfunction in RNA processing.

PMID- 14963486
TI  - Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane
      fusion conformation.
AB  - Enveloped viruses enter cells via a membrane fusion reaction driven by
      conformational changes of specific viral envelope proteins. We report here the
      structure of the ectodomain of the tick-borne encephalitis virus envelope
      glycoprotein, E, a prototypical class II fusion protein, in its trimeric low-pH
      induced conformation. We show that, in the conformational transition, the three
      domains of the neutral-pH form are maintained but their relative orientation is
      altered. Similar to the postfusion class I proteins, the subunits rearrange such
      that the fusion peptide loops cluster at one end of an elongated molecule and the
      C-terminal segments, connecting to the viral transmembrane region, run along the
      sides of the trimer pointing toward the fusion peptide loops. Comparison with the
      low-pH-induced form of the alphavirus class II fusion protein reveals striking
      differences at the end of the molecule bearing the fusion peptides, suggesting an
      important conformational effect of the missing membrane connecting segment.

PMID- 14963487
TI  - A differential role for actin during the life cycle of Trypanosoma brucei.
AB  - Actin is expressed at similar levels but in different locations in bloodstream
      and procyclic forms of Trypanosoma brucei. In bloodstream forms actin colocalizes
      with the highly polarized endocytic pathway, whereas in procyclic forms it is
      distributed throughout the cell. RNA interference demonstrated that in
      bloodstream forms, actin is an essential protein. Depletion of actin resulted in
      a rapid arrest of cell division, termination of vesicular traffic from the
      flagellar pocket membrane leading to gross enlargement of the pocket, loss of
      endocytic activity and eventually cell death. These results indicate that actin
      is required for the formation of coated vesicles from the flagellar pocket
      membrane, which is the first step in the endocytic pathway. Although loss of
      actin in procyclic cells did not affect growth, the trans region of the Golgi
      became distorted and enlarged and appeared to give rise to a heterogeneous
      population of vesicles. However, the flagellar pocket was not affected. These
      findings suggest that trypanosomes have different functional requirements for
      actin during the bloodstream and procyclic phases of the life cycle.

PMID- 14963488
TI  - Asynchronous basepair openings in transcription initiation: CRP enhances the rate
      limiting step.
AB  - The mechanism of isomerization (basepair openings) during transcription
      initiation by RNA polymerase at the galP1 promoter of Escherichia coli was
      investigated by 2-aminopurine (2,AP) fluorescence. The fluorescence of 2,AP is
      quenched in DNA duplex and enhanced when the basepair is distorted or deformed.
      The increase of 2,AP fluorescence was used to monitor basepair distortion at
      several individual positions in the promoter. We observed that basepair
      distortions during isomerization are a multi-step process. Three distinct
      hitherto unresolved steps in kinetic terms were observed, where significant
      fluorescence change occurs: a fast step with a half-life of around 1 s, which is
      followed by two slower steps occurring with a half-life in the range of minutes
      at 25 degrees C. Contrary to commonly held expectations, basepairs at different
      positions opened by 2,AP assays without any obvious pattern, suggesting that
      basepair opening is an asynchronous multi-step process. cAMP.CRP, which activates
      transcription at galP1, enhanced the rate-limiting step.

PMID- 14963489
TI  - Transcriptional regulation of BMP4 synexpression in transgenic Xenopus.
AB  - Synexpression groups are genetic modules composed of genes that share both a
      complex expression pattern and the biological process in which they function.
      Here we investigate the regulation of BMP4 synexpression by studying the
      enhancers of bambi, smad7 and vent2 in Xenopus. We find that a BMP4 synexpression
      promoter module is compact and (i) requires direct BMP responsiveness through
      Smad and Smad-cofactor binding motifs, (ii) may contain an evolutionary conserved
      BMP-responsive element, bre7 (TGGCGCC), that is crucial for expression of bambi
      and smad7 and is highly prognostic for novel BMP-responsive enhancers (BREs); and
      (iii) requires a narrow window of BMP inducibility, because minor enhancement or
      reduction of BMP responsiveness abolishes synexpression. Furthermore, we used a
      bioinformatic model to predict in silico 13 novel BREs, and tested five of them
      that were found in the id1-4 genes. The results highlight that in vivo analysis
      is required to reveal the physiological, spatio-temporal regulation of BMP
      responsive genes.

PMID- 14963490
TI  - Chromatin inheritance upon Zeste-mediated Brahma recruitment at a minimal
      cellular memory module.
AB  - Polycomb group and trithorax group proteins maintain the memory of repressed and
      active chromatin states by regulating chromatin of their target genes via DNA
      sequences termed Polycomb- and trithorax response elements. Since these elements
      often overlap and are able to convey the memory of both silent and active
      chromatin through cell division, they were also defined as cellular memory
      modules (CMMs). We identify here a minimal CMM of 219 bp from the Drosophila Fab
      7 region that regulates the homeotic gene Abdominal-B. This CMM conveys the
      inheritance of active chromatin states induced by an embryonic pulse of
      transcriptional activation via recruitment of the trithorax group proteins
      Trithorax (TRX) and Brahma (BRM), the Drosophila homologue of the SWI2/SNF2
      ATPase involved in chromatin remodelling. Within this CMM, DNA-binding sites for
      the Zeste protein are necessary for the inheritance of active chromatin through
      Zeste-dependent recruitment of BRM, while TRX can bind the CMM even in their
      absence. Thus, epigenetic inheritance of active chromatin states involves the
      recruitment of multiple cooperative chromatin-modifying complexes at closely
      spaced but distinct sites within a CMM.

PMID- 14963491
TI  - A lysosomal tetraspanin associated with retinal degeneration identified via a
      genome-wide screen.
AB  - The Drosophila visual system has provided a model to study phototransduction and
      retinal degeneration. To identify new candidate proteins that contribute to these
      processes, we conducted a genome-wide screen for genes expressed predominately in
      the eye, using DNA microarrays. This screen appeared to be comprehensive as it
      led to the identification of all 22 eye-enriched genes previously shown to
      function in phototransduction or implicated in retinal degeneration. In addition,
      we identified 93 eye-enriched genes whose roles have not been previously defined.
      One of the eye-enriched genes encoded a member of a large family of transmembrane
      proteins, referred to as tetraspanins. We created a null mutation in the eye
      enriched tetraspanin, Sunglasses (Sun), which resulted in light-induced retinal
      degeneration. We found that the Sun protein was distributed primarily in
      lysosomes, and functioned in a long-known but poorly understood phenomenon of
      light-induced degradation of rhodopsin. We propose that lysosomal tetraspanins in
      mammalian cells may also function in the downregulation of rhodopsin and other G
      protein-coupled receptors, in response to intense or prolonged agonist
      stimulation.

PMID- 14963492
TI  - Cloning and analysis of human UroplakinII promoter and its application for gene
      therapy in bladder cancer.
AB  - The differential expression of the desired gene product in the target tissue is
      central for gene therapy. One approach is to use a tissue-specific promoter to
      drive therapeutic gene expression. UroplakinII (UPII) is a urothelium-specific
      membrane protein. To investigate the feasibility of targeting gene therapy for
      bladder cancer, a DNA fragment of 2542-bp upstream of the UPII gene was amplified
      by PCR and linked to a promoterless firefly luciferase reporter gene. The
      transient transfection showed that the DNA fragment resulted in preferential
      expression in bladder carcinoma cells, with negligible expression in
      nonurothelium cells. Furthermore, the DNA segment located between -2545 and -1608
      decided the tissue-specificity of the UPII promoter, the segment located between 
      328 and -4 being the core promoter of UPII. We generated two recombinant
      adenoviruses under the control of the UPII promoter: Ad-hUPII-GFP, carrying green
      fluorescence protein (GFP), and Ad-hUPII-TNF, carrying the tumor necrosis factor
      alpha (TNFalpha). ELISA revealed that the secretion of TNFalpha by Ad-hUPII-TNF
      infected bladder cancer cells was significantly higher than Ad-hUPII-TNF-infected
      nonurothelium cells. The conditioned medium from Ad-hUPII-TNF-infected bladder
      cancer cells apparently inhibited the proliferation of L929 cells, a TNFalpha
      sensitive cell line, comparing to Ad-hUPII-TNF-infected nonurothelium cells.
      Intravesical inoculation with Ad-hUPII-TNF inhibited tumor growth in the
      orthotopic human bladder cancer model. The sustained high level of TNFalpha in
      urine was identified with ELISA. Taken together, these data suggest that most of
      the cis elements that confer the bladder-specificity and differentiation
      dependent expression of the human UPII gene reside in the 2542-bp sequence, and
      TNFalpha driven by the human UPII (hUPII) promoter is effective in the specific
      inhibition of bladder cancer growth both in vivo and in vitro. These results may
      yield a new therapeutic approach for bladder cancer and provide information on
      the molecular regulation of urothelial growth, differentiation, and disease.

PMID- 14963493
TI  - [Passive smoking--active debate].

PMID- 14963494
TI  - [Specialized cardiology services and overall treatment].

PMID- 14963495
TI  - [Safety with good emergency services].

PMID- 14963496
TI  - [Is the family practice system successful?].

PMID- 14963497
TI  - [Monopoly of the methadone treatment].

PMID- 14963498
TI  - [Causes of postoperative mortality after lung cancer surgery].
AB  - BACKGROUND: There is a relatively high postoperative mortality after lung cancer
      surgery. However, the alternative is almost 100% mortality within five years if
      surgery is not performed. MATERIAL AND METHODS: This study is based on data in
      the Cancer Registry of Norway and information from hospitals where the patients
      had been treated. From 1993 to 2000, 2528 patients with lung cancer were operated
      with lung resection. RESULTS: A total of 188 patients died within 60 days. In 54
      of them the cause of death was respiratory failure or pneumonia. There were nine
      cases with serious intraoperative bleeding with seven deaths, six on the table.
      Further postoperative bleeding occurred in 27 cases, most often after
      pneumonectomy. Of these, 10 died because of the bleeding. For 15 patients the
      cause of death was bronchopleural fistula, of which 13 had been operated with
      pneumonectomy. Myocardial infarction or cardiac failure caused the death of 32
      patients. An additional 70 patients died from other complications.
      INTERPRETATION: Postoperative fatal complications after lung resection for cancer
      are too high.

PMID- 14963499
TI  - [Public access defibrillators--beneficial?].
AB  - BACKGROUND: In Norway, every year more than 3000 persons suffer sudden cardiac
      death caused by ventricular fibrillation. The present recommendations of
      international expert committees are that the use of public-access defibrillators
      should be encouraged, including training of non-medical personnel. MATERIAL AND
      METHOD: In order to evaluate the validity of such recommendations, we performed
      searches in Medline on relevant keywords and evaluated articles thus identified
      and their references. We selected studies on countries, cities, public access
      defibrillator projects, and on epidemiology of cardiac arrest and ventricular
      fibrillation. RESULTS: Studies of the public-access defibrillation strategy
      reported the highest frequencies of survival. Studies from cities gave highly
      variable results; those for entire countries poor results. Different populations
      have different results of survival, and commonly used predictor models do not
      comprehensibly explain these findings. Over time there is a falling frequency of
      ventricular fibrillation as the cause of cardiac arrest. INTERPRETATION:
      Application of the strategy of public-access defibrillators will not result in
      significantly improved survival from cardiac arrest in Norway.

PMID- 14963500
TI  - [Laymen groups trained to use defibrillators in rural areas?].
AB  - Patients suspected of having an acute myocardial infarction (AMI) constitute a
      group with particularly high risk of developing cardiac arrest caused by
      ventricular fibrillation (VF). It is conceivable that a strategy of shortening
      the interval until defibrillation skills are brought to the patient can be more
      fruitful in rural areas than the now prevailing recommendations of obtaining
      rapid defibrillation after cardiac arrest is manifest. A project is being
      organized in a Norwegian rural municipality, where laymen are being trained in
      the use of automated external defibrillators (AEDs), and are organized in groups
      according to place of residence or work. Their main task is to bring the AED to
      patients with suspected AMI and be prepared to use the AED if cardiac arrest
      should supervene. The main objective of a planned five-year study is to gather
      information as to what degree of mastering and what degree of stress the
      participants of the project experience, and to see if it is possible to maintain
      an organisation like this over a longer period of time. Preliminary results from
      the first half-year of the project indicate that the participants are entering
      the project with a reasonable degree of individual self-confidence and have even
      greater confidence in the group to which they belong. This might suggest that it
      is an advantage for participants in AED projects to be organised in groups in
      which mutual support is experienced.

PMID- 14963501
TI  - [Cardiopulmonary resuscitation in municipal health services--a simple program for
      training and maintenance].
AB  - BACKGROUND: Cardiopulmonary resuscitation (CPR) with defibrillation may be a life
      saving procedure. We present a course for CPR training and skills preservation
      developed by local paramedics and GPs and aimed at primary care professionals.
      MATERIAL AND METHODS: In a three-hour course programme for 10-16 participants we
      simulate emergency scenarios with an advanced computerised phantom as patient.
      Participants work in teams with physicians, ambulance personnel and nurses
      responsible for defibrillation and medication, with the other participants
      providing basic cardiopulmonary resuscitation. Constructive feedback based on the
      national guidelines follows every training session. Instructors are the ambulance
      leader and a GP. RESULTS AND INTERPRETATION: The training is well received and
      courses fully booked. The optimal number of physicians is two to four. The
      success of the course suggests that there is a motivation for quality improvement
      in CPR in Norwegian local communities.

PMID- 14963502
TI  - [Urgent calls--prehospital response time in Vestfold and Troms in 2001].
AB  - BACKGROUND: Targeted emergency medical responses with minimum time loss require a
      well organized emergency medical system (EMS). We studied time consumption from
      emergency call reception to the arrival of the ambulance unit in two dispatch
      centres serving two demographically different Norwegian regions. MATERIAL AND
      METHODS: We analysed 5004 emergency "code red" calls during 2001 processed by an
      EMS serving 367 000 inhabitants in 28 mixed urban/rural municipalities in
      Vestfold and Troms counties. Dispatch centre process time, ambulance (ground, air
      or boat) response time and total access times were measured. RESULTS: Total pre
      hospital access time from call reception to arrival of ambulance to patient were
      considerably longer than the suggested national goals, which were only met in two
      rural areas out of the 28 municipalities studied. Median pre-hospital response
      time was 10 minutes in both regions. Within 12 minutes from the emergency call,
      62.9% of the population in Vestfold and 59.8% in Troms were reached by ambulance.
      INTERPRETATION: National standards for pre-hospital response times in medical
      emergencies are neither met in densely populated cities, nor in less populated
      rural areas.

PMID- 14963503
TI  - [Opiate users in methadone-assisted rehabilitation one year and two years after
      admission].
AB  - BACKGROUND: Norway has recently established a nationwide system for methadone
      assisted rehabilitation of opiate users, but few studies have been undertaken to
      investigate outcome. MATERIAL AND METHODS: 75 opiate users in Oslo were
      interviewed at start of treatment and at follow-ups one and two years later in
      1999-2002. The main instruments at all three points were EuropASI and SCL-25.
      MCMI-II was additionally used at the start. RESULTS: Five patients (7%) died
      during the two-year observation period; 24 patients (34%) dropped out of
      treatment. A significant and stable reduction in the use of opiates, as well as
      for criminality and prostitution, was found. No changes in the use of other
      substances, economic status and employment status were found. Depressive symptoms
      increased significantly during the last year. INTERPRETATION: The data indicate
      that the speed at which new patients started treatment came at the sacrifice of
      psychosocial rehabilitation.

PMID- 14963504
TI  - [Methadone dose, treatment duration and heroin use in drug-assisted
      rehabilitation].
AB  - BACKGROUND: Medication-assisted rehabilitation is established as a nationwide
      treatment option for opioid addicts. MATERIAL AND METHOD: A pilot study using a
      recently developed evaluation inventory was conducted in the autumn of 2001. Data
      on 303 methadone patients from the eastern health region formed the basis of
      evaluation. RESULTS: The sample mean methadone dose was 111 mg, with a lower
      dosage level in Oslo than in the other counties. On average, the patients had
      been treated for 22.4 months. 125 (41%) patients had used non-prescribed opioids
      the last four weeks. Use of heroin was more prevalent among the Oslo patients
      (49%) than in the other counties (24%). Heroin use was significantly associated
      with geography, sex (higher prevalence among men) and methadone dose (higher
      prevalence at methadone doses < or = 105 mg). There was a negative relationship
      between treatment duration and use of heroin among the Oslo patients.
      INTERPRETATION: In an international perspective, this sample has a generally high
      dosage level, long treatment duration and good treatment outcomes. Heroin
      abstinence is more difficult to achieve in Oslo than in the rest of the region,
      especially in the early phases of treatment.

PMID- 14963505
TI  - [Scrotal pain and Henoch-Schonlein purpura].
AB  - An acute scrotum is a potential urologic emergency and requires urgent evaluation
      in order to rule out conditions that need immediate surgical management. The most
      important condition to rule out is torsion of the testis. In cases of less
      emergency, a wide variety of differentials may be considered. Scrotal pain or
      swelling may occur in 10 to 15% of boys with Henoch-Schonlein purpura. We present
      the case of a 19-year-old boy who had intermittent scrotal pain of two weeks'
      duration with acute exacerbation prior to admission. The clinical examination
      gave no specific results. A regular and Doppler sonographic scan showed no
      evidence of testicular affection. The patient was observed in hospital. Two years
      earlier he had present with abdominal cramps, rectal bleeding, duodenitis,
      proteinuria and a purpuric rash, suggestive of Henoch-Schonlein purpura; IgA
      nephritis was proven after a renal biopsy. As all other differentials had been
      ruled out, we concluded that Henoch-Schonlein syndrome was the cause of the
      recurrent scrotal pain in our patient.

PMID- 14963506
TI  - [Use of opioids against severe cancer pain].

PMID- 14963507
TI  - [Exercise ECG].
AB  - Exercise ECG testing is the most widely used method for detecting myocardial
      ischaemia, but the test is also applied in numerous other settings. The method
      requires close attention to technical details and application of appropriate test
      protocols. Attention to absolute and relative contraindications and criteria for
      test abortion is mandatory. In addition to the ECG, work capacity, heart rate and
      blood pressure responses are also important diagnostic and prognostic markers.
      Interpretation of the test results depends on the setting; knowledge of potential
      confounders is important. The diagnostic and prognostic value of the test is
      population-dependent. Exercise ECG testing is most valuable as a diagnostic tool
      for myocardial ischaemia when pretest disease probability is high.

PMID- 14963508
TI  - [Stress echocardiography].
AB  - BACKGROUND: In stress echocardiography, ischaemia is detected as wall motion
      abnormalities. The test can be done both with exercise (which is the more
      sensitive) and pharmacological stress (which is more specific). MATERIAL AND
      METHODS: The paper gives an overview of the method, of diagnostic and prognostic
      value as well as indications and contraindications, based on present literature.
      RESULTS AND INTERPRETATION: The sensitivity is 80-90%, specificity 75-100%,
      dependent on the extent and degree of disease. A negative test predicts a low
      cardiac event rate of about 1% per year and a low preoperative cardiac risk. The
      diagnostic accuracy is dependent on optimal equipment quality and on the
      experience of the examiner. Without specific training, sensitivity is about the
      same as with exercise ECG. The complication rate is low, dependent on the type of
      stress. Stress echocardiography is useful in patients unable to exercise, in
      preoperative risk assessment and in suspected false-negative exercise ECG. In
      addition it is a supplement to coronary angiography for evaluation of the
      significance of intermediate stenoses, to identify culprit lesion and for
      viability detection. Finally, it is useful in aortic stenosis with reduced left
      ventricular function for evaluation of stenosis and contractile reserve.

PMID- 14963509
TI  - [Clinical use of new echocardiographic techniques].
AB  - New applications and further development of current methods have contributed to
      the increasing importance of ultrasound diagnostics in cardiology. Quantitative
      assessment of regional myocardial function has been made possible by tissue
      Doppler, which is of particular importance in coronary artery disease.
      Visualisation and functional assessment of the left ventricle can be improved by
      contrast echocardiography when conventional imaging is unsatisfactory.
      Intravascular ultrasound has provided important information on coronary
      atherosclerosis and thus contributed significantly to the development of
      percutaneous coronary interventions. Percutaneous interventional treatment for
      arrhythmias, valve stenoses and septal defects can be guided by intracardiac
      echocardiography. Three-dimensional echocardiography may add important
      information to two-dimensional findings, with significant potential for clinical
      use, particularly in congenital heart disease and acquired valve disease.

PMID- 14963510
TI  - [337 home calls during daytime from the emergency medical center in Oslo].
AB  - BACKGROUND: Few studies have addressed physicians' home calls in Norway. The aim
      of this study is to analyse home calls during daytime in Oslo in relation to
      patients (age, sex, district), diagnoses, request procedures, and clinical
      outcome. METHODS AND MATERIAL: General practitioners in the City of Oslo
      emergency medical centre recorded their home calls during three months using a
      standardised form. RESULTS: Calls to 337 patients (mean age 70, median 77 years;
      two thirds females; seven to children below two years of age) were recorded. The
      home calls were requested by relatives (36%), the patients themselves (32%),
      community care nurses (11%), and nursing homes (7%). The assessments made by the
      operators of the medical emergency telephone were generally correct. Physicians
      reported 77% full and 20% partial match between reported and found medical
      problem. The physicians assessed that 22% of the patients would have been able to
      go and see a doctor. 39% of all patients were admitted to hospital, 34 % needed
      ambulance transportation. The admitting GPs received hospital reports only after
      27% of admissions. INTERPRETATION: Access to acute home calls by a physician
      during daytime is a necessary function in an urban public health service.

PMID- 14963511
TI  - [Physicians' work situation a year after the list patient system reform].
AB  - BACKGROUND: We describe general practitioners' (GPs') degree of satisfaction with
      the recently introduced Norwegian list patient system, based on information
      provided by GPs on the number of patients on their lists and their own assessment
      of their work situation. MATERIAL AND METHODS: Data were collected by an
      extensive questionnaire survey among GPs in the list patient system during the
      autumn of 2002. A total of 2306 GPs returned the questionnaire (70% response
      rate). RESULTS: Most GPs were satisfied with the list patient system. 60% were
      satisfied with the number of patients on their list, 21% wanted more patients;
      19% would have liked to have fewer patients. In general GPs feel that they have
      enough time for each patient and that it is not difficult to fit emergency cases
      into their daily schedule. About half of them are of the opinion that the list
      patient system has not given them a better insight into their patients' medical
      needs or better treatment options. INTERPRETATION: Most GPs were satisfied with
      the new system and with the number of patients on their list. The importance to
      patients of being assigned to one GP is highlighted by the fact that GPs think
      they can do a better job when the practice has a high proportion of regular
      patients.

PMID- 14963512
TI  - [Change in service provision and availability under the list patient system
      reform].
AB  - BACKGROUND: In this article, we analyse the relationship between length of
      patient lists and general practitioners' (GPs') service provision in order to
      investigate whether the list patient system reform has led to reduced
      accessibility and/or supplier inducement. MATERIAL AND METHODS: The data were
      collected from a comprehensive questionnaire survey among GPs in the list patient
      system in 2002 (2306 GPs) and from the National Insurance Administration in 2001
      (1637 GPs). The relationship between length of patient lists and service
      provision was analysed using regression analysis. RESULTS: The relationship
      between length of patient lists and number of consultations per GP was almost
      proportional, as was the relationship between length of patient list and number
      of consultations initiated by GPs. GPs who wanted more patients on their list had
      fewer consultations than those who were satisfied with the length of their lists
      and they did not compensate by taking more laboratory tests per consultation.
      Analysis of the two independent sets of data gave almost identical results.
      INTERPRETATION: Patients' access to their GPs is independent of the length of his
      or her patient list. Even GPs with long lists do not ration consultations. This
      probably reflects efficient organisation of the practice. Our results do not
      support the theory that GPs induce demand for their services; one explanation is
      that GPs with short lists have chosen to have precisely that and have no need to
      induce demand.

PMID- 14963513
TI  - [The new list patient system and emergency service in Bergen].
AB  - BACKGROUND: The purpose of this study was to explore the attitudes of patients
      seeking emergency care, with special emphasis on the role of the recently
      introduced list patient system. MATERIAL AND METHOD: During a twelve-day period
      in January 2003, patients seeking emergency care in Bergen, Norway were asked to
      fill in a questionnaire that explored whether they knew the name of the physician
      on whose list they were, their assessment of the accessibility of this physician,
      whether they had tried to contact him or her prior to coming in for emergency
      care, why they had contacted emergency care, and if they were willing to wait one
      or several days for a consultation if they were certain to get an appointment
      with their own physician. RESULTS: 1504 questionnaires were analyzed (72% of the
      study population). Most patients knew the name of their physician (84%) and were
      reasonably satisfied with his or her accessibility. Nevertheless, three in four
      patients had not tried to contact their physician prior to coming in to the
      emergency centre. Half of them were willing to wait until the next day to see
      their personal physician. INTERPRETATION: There is a considerable potential for
      change of patient behaviour in primary care emergencies.

PMID- 14963514
TI  - [Time to establish a national registry of cardiovascular diseases].

PMID- 14963517
TI  - [Tetralogy of Fallot and collapse of the Soviet Union].

PMID- 14963518
TI  - [Risk of lung cancer and heart disease in passive smoking].

PMID- 14963519
TI  - [Social medicine and the preventive health care work].

PMID- 14963520
TI  - [New trends in the treatment of obesity].

PMID- 14963521
TI  - [Are local steroid injections effective or not?].

PMID- 14963523
TI  - [Polymyalgia rheumatica and questionnaires].

PMID- 14963524
TI  - [To smoke or not to smoke].

PMID- 14963525
TI  - [Scientific misconduct].

PMID- 14963527
TI  - [The Medical Society and hospital financing].

PMID- 14963530
TI  - [Vaccination of patients with allergy].

PMID- 14963532
TI  - [Addicts and drugs].

PMID- 14963535
TI  - [National Health Innovation System: relations between scientific fields and
      economic sectors].
AB  - Health Science and Technology is currently the subject matter of government and
      university actions. Such actions should converge to the establishment of a
      National Health Innovation System, which still calls for acknowledgment from the
      economic sector counterpart. A study was carried out with the purpose of
      describing the relations between scientific fields and economic sectors as a
      means of learning more about this System. Records from the Brazilian Directory of
      Research Groups (version 4.1) were examined and selected when Health was a
      keyword either to field of knowledge or economic sector. Data were compiled into
      multiresponse variables and analyzed in contingency tables using residual,
      correspondence, and cluster analyses. It was found that the Brazilian National
      Health Innovation System constitutes a sectorial system where competitiveness is
      more socially than economically-oriented, making this System favorably in tandem
      with the National Unified Health System as well as responsive to public policies
      focused on social welfare.

PMID- 14963536
TI  - [Maternal complications associated with type of delivery in a university
      hospital].
AB  - OBJECTIVE: To analyze maternal complications associated to type of delivery,
      comparing cesarean (c-) section with vaginal delivery. METHODS: Retrospective
      study of 1,748 deliveries carried out at a university hospital in the city of S o
      Paulo, Southeastern Brazil, in which the newborn weighed more than 500 g.
      Maternal complications occurred during delivery as well as those diagnosed during
      puerperium that required further hospital admission were analyzed. Statistical
      analyses included Student's t test and Fisher's Exact test. Significance level
      was set at 0.05. RESULTS: C-sections were performed on 988 patients (56.5%).
      Hemorrhagic complications occurred in 1.2% of c-sections and in 0.8% of normal
      deliveries, with no statistically significant difference between both groups.
      Endometritis was observed in 0.4% of c-sections and in 0.1% of vaginal
      deliveries, without statistically significant difference. Two cases of puerperal
      infection evolved to hysterectomies, in the c-section group. There were no
      maternal deaths related to c-section. CONCLUSIONS: No associations were found
      between maternal complications and type of delivery in the period analyzed.

PMID- 14963537
TI  - [Impact of underlying causes of death on life expectancy in Salvador and Sao
      Paulo, Brazil, 1996].
AB  - OBJECTIVE: To evaluate and compare the impact of some underlying causes of death
      on life expectancy of residents in two metropolitan areas. METHODS: It was
      carried out a cross-sectional descriptive ecological study based on official data
      (deaths and populations) and estimates of residents in the cities Salvador and
      Sao Paulo, Brazil, in 1996. The impact of different causes of death on life
      expectancy was evaluated by means of competitive risks and life tables. RESULTS:
      Life expectancy for males at birth in both cities (64.1 years in Salvador and
      63.4 years in Sao Paulo) was lower than for females (70.3 years in Salvador and
      73.9 years in Sao Paulo). Communicable diseases have a major impact on the
      mortality in the first years of age, external causes are very important
      especially for men in intermediate ages, and cardiovascular diseases have a main
      role in elderly. Ranked by decreasing importance, causes of death for males in
      both cities were cardiovascular diseases, external causes, neoplasms, respiratory
      diseases and infectious and parasitic diseases. For females, the most important
      were cardiovascular diseases, then neoplasms, respiratory diseases, infectious
      and parasitic diseases, and external causes. CONCLUSIONS: The well-known social
      gap between the two capitals affects first the basic level, from availability and
      quality of public services to data provided by these services, which impair a
      more detailed analysis.

PMID- 14963538
TI  - [Risk factors for small-for-gestational age births among infants in Brazil].
AB  - OBJECTIVE: To assess the risk factors for small-for-gestational-age (SGA) births.
      METHODS: All live births occurring in the city of Pelotas, Brazil, between
      October and December 1993 were identified and mothers interviewed soon after
      delivery. Birthweight was recorded by the maternity staff. Gestational age was
      obtained from the mothers' recall of their date of last menstrual period. SGA was
      defined as a birthweight below the 10th percentile for gestational age and sex,
      according to the reference developed by Williams. Chi-square test and logistic
      regression were used in the crude and multivariate analysis, respectively.
      RESULTS: In all, 1082 births were identified. The prevalence of SGA was 13.1%.
      Even after adjusting for possible confounding variables, the odds ratio for SGA
      among those infants whose family income was <1 minimum wage was 8.81 (95% CI,
      1.12-69.46) times higher than among those for infants with a family income > or =
      minimum wage. An antenatal care of low quality was associated with an odds ratio
      of 3.28 (95% CI, 1.09-9.91) for SGA. Short maternal stature and maternal smoking
      during pregnancy were also associated with SGA births. CONCLUSIONS: Low
      socioeconomic status, maternal smoking during pregnancy, maternal height and an
      antenatal care of low quality are the main risk factors for SGA births.

PMID- 14963539
TI  - [Temporal pattern of diarrhea hospitalizations and deaths in children, 1995 to
      1998, Brazil].
AB  - OBJECTIVE: To analyze the temporal pattern of hospitalization and deaths due to
      diarrhea among children less than five years old between 1995 and 1998 to support
      specific prevention actions and disease control strategies. METHODS: Data was
      collected from the Ministry of Health's Mortality Data System and Hospitalization
      Data System. Monthly time series of diarrhea hospitalizations and deaths were
      decomposed into stochastic linear trend, deterministic seasonal and irregular
      components using structural time series models. RESULTS: The levels of both
      series showed a decline in time. This pattern being more evident in the
      hospitalization series. The slope variation was constant in both series; on
      average less than 5.3 hospitalizations/month (p-value <0.001), and less than 1
      death/month (p-value <0.1). The residual analysis of the hospitalization series
      revealed a positive trend change in January 1996. The seasonal component for both
      models was statistically significant (p-value <0.0001) with May and June as
      months of highest hospitalizations and deaths. Normality and time independence
      assumptions of errors could not be rejected at a 0.05 significance level.
      CONCLUSIONS: The temporal pattern of moderate and severe diarrhea described and
      estimated in this study suggests that rotavirus might be a predominant disease
      agent. In this context, targeted vaccination is recommended for prevention and
      control. However, further studies on the efficacy of rotavirus candidate vaccines
      are necessary in order to implement this strategy in Brazil.

PMID- 14963540
TI  - [Mortality among children enrolled in public day care centers in Brazil].
AB  - OBJECTIVE: To describe the mortality pattern among children enrolled in public
      day care centers. METHODS: This was a descriptive study of the mortality pattern
      among children aged from 0 to 6 years and 11 months who were enrolled in all the
      public day care centers in the city of Sao Paulo, Brazil, from 1995 to 1999. The
      variables of interest were sex, age, underlying cause of death, duration of day
      care attendance and seasonality. RESULTS: The average mortality rate for the
      period was 36.4 per 100,000 children. Of the total number of deaths, 32.7% were
      among children under 1 year old and 78.4% under 3 years old. The deaths of 54.2%
      of these children occurred before completing six months in the day care center,
      with a concentration of 36.3% during the first three months. The majority of the
      deaths occurred during the winter and autumn seasons: 31.8% and 29.6%,
      respectively. The main underlying causes of death were infections: pneumonia
      (29.6%), meningococcal disease (13.0%), non-meningococcal meningitis (8.5%),
      gastroenteritis (7.6%) and chickenpox (5.4%). External causes were responsible
      for 13.5% of the deaths and included falls, being run over, drowning, burns and
      physical aggression. CONCLUSIONS: The study indicated that younger children (0-3
      years) were the most vulnerable group and that the majority of deaths derived
      from avoidable causes, some of which preventable by vaccination nowadays.

PMID- 14963541
TI  - Alcohol drinking patterns by gender, ethnicity, and social class in Bahia,
      Brazil.
AB  - OBJECTIVE: To study patterns of alcohol consumption and prevalence of high-risk
      drinking. METHODS: A household survey was carried out in a sample of 2,302 adults
      in Salvador, Brazil. Cases of High-Risk Drinking (HRD) were defined as those
      subjects who referred daily or weekly binge drinking plus episodes of drunkenness
      and those who reported any use of alcoholic beverages but with frequent
      drunkenness (at least once a week). RESULTS: Fifty-six per cent of the sample
      acknowledged drinking alcoholic beverages. Overall consumption was significantly
      related with gender (male), marital status (single), migration (non-migrant),
      better educated (college level), and social class (upper). No significant
      differences were found regarding ethnicity, except for cachaca (Brazilian
      sugarcane liquor) and other distilled beverages. Overall 12-month prevalence of
      high-risk drinking was 7%, six times more prevalent among males than females
      (almost 13% compared to 2.4%). A positive association of HRD prevalence with
      education and social class was found. No overall relationship was found between
      ethnicity and HRD. Male gender and higher socioeconomic status were associated
      with increased odds of HRD. Two-way stratified analyses yielded consistent gender
      effects throughout all strata of independent variables. CONCLUSIONS: The findings
      suggest that social and cultural elements determine local patterns of alcohol
      drinking behavior. Additional research on long-term and differential effects of
      gender, ethnicity, and social class on alcohol use and misuse is needed in order
      to explain their role as sources of social health inequities.

PMID- 14963542
TI  - [Relationship between psychosocial job satisfaction and health in white collar
      workers].
AB  - OBJECTIVE: To identify whether psychosocial satisfaction at work is associated
      with workers' health and to verify if sociodemographic characteristics have an
      impact on these associations. METHODS: A cross-sectional study was carried out in
      224 employees of a private managed care and retirement savings company in Sao
      Paulo, Brazil. Four self-administered questionnaires on sociodemographic
      features, job satisfaction, and health (physical, mental, and work ability) were
      applied. Variables associations were analyzed using t-Student, Mann-Whitney and
      Kruskal-Wallis tests, Spearman correlation coefficient, and multiple linear
      regression analysis. RESULTS: Job satisfaction was associated with duration in
      the company (p <0.001) and job position (p=0.003), where greater satisfaction was
      observed among workers with shorter duration in the company and those in managing
      positions. Job satisfaction was associated with mental health and work ability
      (vitality: p<0.001; social aspects: p=0.055; emotional aspect: p=0.074; mental
      health: p<0.001; and work capacity: p=0.001). CONCLUSIONS: Job satisfaction is
      associated with workers' health regarding their "mental health" and "work
      ability", showing the importance of psychosocial factors for their health and
      well-being. Changes are suggested in work conception and organization to focus
      psychosocial factors. Longitudinal studies are recommended to investigate the
      causal direction of these associations.

PMID- 14963543
TI  - [Prevalence and severity of domestic violence among pregnant women, Mexico].
AB  - OBJECTIVES: To determine whether pregnancy is a risk factor for domestic violence
      and to compare prevalence and severity of violence reported by women before and
      during pregnancy. METHODS: There were interviewed 468 women in the third
      trimester of pregnancy who were seen during prenatal visits at public clinics in
      the state of Morelos, Mexico. Emotional, physical and sexual violence were
      investigated. A severity index was built up. Logistic regression analysis was
      applied in order to identify the main variables associated to domestic violence
      during pregnancy. RESULTS: The prevalence of domestic violence did not change
      significantly before and during pregnancy (32%). The prevalence of each type of
      violence remained the same. About 27% of women who reported violence during
      pregnancy did not have experience it before, and a comparable proportion had
      experienced violence before but not during pregnancy. The severity of emotional
      violence significantly increased during pregnancy (compared to the previous year)
      whereas the severity of physical violence decreased. Variables most clearly
      related to violence during pregnancy were: couple's past history of child abuse;
      women witnessing domestic violence during childhood; and violence in the year
      before pregnancy. Several risk scenarios were identified, which could be helpful
      for health care providers. CONCLUSIONS: The results showed that emotional
      violence is more prevalent than physical and sexual violence, allowing for a
      better understanding of this phenomenon.

PMID- 14963544
TI  - [Antischistosomal activity of artemether in experimental Schistosomiasis
      mansoni].
AB  - OBJECTIVE: To evaluate the effect of intramuscular injection of artemether in
      mice experimentally infected with Schistosoma mansoni, at the time of infection,
      during schistosomula maturation and after the beginning of egg-laying. METHODS:
      Eighty adult females Balb/c mice were divided into 8 groups with 10 animals each.
      Seven groups were infected with S. mansoni using 60 cercariae for each animal,
      inoculated subcutaneously, and the remaining group was maintained without
      infection. Among the seven infected groups, six were treated with artemether,
      according to the following schedule: three groups received doses of 100 mg/kg on
      days 0, 20 or 60 after inoculation of the cercariae; the other three received 50
      mg/kg of artemether, also on days 0, 20 or 60. At the end of the 9th, 10th and
      11th weeks after infection all the mice infected with S. mansoni were submitted
      to fecal examination using the Kato-Katz technique. On the 80th day of the
      experiment, the surviving animals were sacrificed and submitted to perfusion of
      the portal system in order to recover the worms. Body, liver and spleen weights
      of each animal were determined at that time. RESULTS: A reduction in egg-laying
      and the number of worms recovered was observed in mice treated with artemether
      (50 or 100 mg/kg) on the 20th day after infection. The decrease in the number of
      worms was more notable among S. mansoni females. A significant decrease in liver
      and spleen weights was also seen on the 20th day among animals treated with 50 or
      100 mg/kg of artemether and also among those that received the drug at a dose of
      50 mg/kg 60 days after infection. CONCLUSIONS: Evidence of the antischistosomal
      activity of artemether was shown, even at a dose of 50 mg/kg, when the drug was
      administered during the schistosomula maturation period in the portal system of
      the vertebrate host.

PMID- 14963545
TI  - [Sexually transmitted diseases symptoms in adults: prevalence and risk factors].
AB  - OBJECTIVE: To evaluate the prevalence of sexually transmitted disease (STD)
      symptoms and associated risk factors in an adult population. METHODS: A
      population-based cross-sectional study was conducted among residents of the
      metropolitan area of Pelotas, Brazil. Subjects were 20 years old or more. A self
      administered questionnaire was used to gather information about sexual behavior
      and STD symptoms. Multivariate analysis was undertaken using logistic regression.
      RESULTS: The prevalence of STDs was 13.5%. A higher risk of STDs was found in non
      white younger women with more sexual partners and who did not use condoms in
      their last sexual relationship. Among men, early initiation of sexual activity
      and anal sex were positively associated with the outcome. Higher risks were found
      among women with lower schooling. CONCLUSIONS: The present study identified a
      significant prevalence of STD symptoms in this population and showed differences
      in risk factors according to gender. Since many STDs are asymptomatic and
      symptomatic cases are often either not perceived as disease by patients or not
      diagnosed in health services, the actual prevalence may be even greater. The
      study results suggest that cohabitation with a sexual partner does not reduce the
      risk of STDs in this population and showed sex differences for risk factors, both
      of which should be taken into account while approaching this issue.

PMID- 14963546
TI  - [Breastfeeding among teenage and adult mothers in Brazil].
AB  - OBJECTIVE: To estimate the prevalence of breastfeeding among teenage (younger
      than 20 years old) and adult mothers of six-month-old children and to identify
      factors associated with weaning. METHODS: A cross-sectional study of a sample of
      237 teenage mothers and 239 adult mothers living in the city of Montes Claros,
      Brazil, whose babies were six-month-old at the time of the interview was carried
      out. Mothers answered a questionnaire at home. To assess factors associated with
      weaning, univariate, Mantel-Haenszel, and multiple logistic regression analyses
      were performed. RESULTS: Breastfeeding prevalence in children aged 6 months was
      71.3% among teenage mothers and 77.4% among adult mothers (crude OR=1.38;
      p=0.128), but after adjusting for control variables the role of adolescence added
      considerable weight to weaning. Factors associated with weaning were: marital
      status, mother's occupation after delivery (both showed interaction with teenage
      years), difficulty to breastfeeding in the first days after delivery, and
      exclusive breastfeeding at the time of hospital discharge. CONCLUSIONS: The
      observed interactions with teenage in regard to weaning suggest that motherhood
      in this age group has unique features that should be further investigated.

PMID- 14963547
TI  - [Falls among older adults seen at a Sao Paulo State public hospital: causes and
      consequences].
AB  - OBJECTIVE: To investigate the history of accidental falls reported by older
      adults, identifying possibly related factors, as well as place of occurrence,
      causes, and consequences. METHODS: The sample investigated included 50 older
      adults, of both sexes, ages 60 years or older, living in the city of Ribeirao
      Preto, Southeastern Brazil, who had been seen at two inpatient units of a public
      hospital. Patient records were examined and household visits carried out for the
      application of a structured questionnaire including open, closed, and mixed
      questions related to the fall. RESULTS: Data obtained show a reality not
      substantially different from that observed in other countries. Most events
      occurred among older women (66%), with mean age 76 years, and at home. Causes
      were mainly related to physical environment (54%), and brought serious
      consequences to the subjects, fractures being the most common outcome (64%).
      Falls had a great impact on subjects' lives in terms of activities such as: lying
      down/getting up, walking on plain surfaces, cutting toenails, bathing/showering,
      walking outside home, taking care of financial issues, shopping, using public
      transportation, and climbing stairs. CONCLUSIONS: The study demonstrated that
      falls occurred among older adults have serious physical, psychological, and
      social consequences, reinforcing the need for fall prevention, in order to ensure
      greater quality of life, autonomy, and independence for the elderly.

PMID- 14963548
TI  - Fluoride and aluminum in teas and tea-based beverages.
AB  - OBJECTIVE: To evaluate fluoride and aluminum concentration in herbal, black,
      ready-to-drink, and imported teas available in Brazil considering the risks
      fluoride and aluminum pose to oral and general health, respectively. METHODS: One
      hundred and seventy-seven samples of herbal and black tea, 11 types of imported
      tea and 21 samples of ready-to-drink tea were divided into four groups: I-herbal
      tea; II-Brazilian black tea (Camellia sinensis); III-imported tea (Camellia
      sinensis); IV-ready-to-drink tea-based beverages. Fluoride and aluminum were
      analyzed using ion-selective electrode and atomic absorption, respectively.
      RESULTS: Fluoride and aluminum levels in herbal teas were very low, but high
      amounts were found in black and ready-to-drink teas. Aluminum found in all
      samples analyzed can be considered safe to general health. However, considering
      0.07 mg F/kg/day as the upper limit of fluoride intake with regard to undesirable
      dental fluorosis, some teas exceed the daily intake limit for children.
      CONCLUSIONS: Brazilian and imported teas made from Camellia sinensis as well as
      some tea-based beverages are sources of significant amounts of fluoride, and
      their intake may increase the risk of developing dental fluorosis.

PMID- 14963549
TI  - [Observation of language, visual and hearing function development in infants].
AB  - OBJECTIVE: To investigate language, visual and hearing function development among
      infants in a day-care center based on educators' assessments. METHODS: One
      hundred and fifteen infants who attended a day-care center at one university of
      the Sao Paulo State, Brazil, were assessed during the period between 1998 and
      2001. The "Protocol for Observation of Language, Visual and Hearing Function
      Development," containing a total of 39 standardized tests, was utilized to assess
      infants from three to twelve months old. The protocol was applied by trained
      educators, members of the day-care center staff. Statistical analysis was carried
      out using Chi-square test or Fischer's exact test at p <0.05. RESULTS: Infants
      showed different language development patterns as for polysyllabic babbling and
      production of first words. For visual function, infants showed a different
      pattern of imitation and initiation in gesture games and following commands with
      gestures. CONCLUSIONS: The day-care center setting is probably promoting a
      distinct pattern of language, visual and hearing function development. Prevention
      in day-care centers should aim at integrating education and health to achieve the
      common purpose of child welfare.

PMID- 14963550
TI  - [Determinants of elders' choice between private and public health care
      providers].
AB  - OBJECTIVE: Elderly choose between utilizing private or public health care
      providers based on their socioeconomic, demographic, and epidemiological
      condition. The purposes of this study was to evaluate how these factors affect
      the choice of health care provider and to compare the impact of their choice on
      individual and family income. METHODS: Data from 7,920 elders interviewed in a
      study of the State Committee for the Elderly of the state of Rio Grande do Sul in
      1995 was used to evaluate the impact of elders' gender, age, educational level,
      individual income, family income, family size, participation in the family total
      income, and health self-assessment when choosing private or public health care
      providers. The statistical analysis was carried out using logistic regression.
      RESULTS: To have access to private health care providers, family income had a
      much more significant impact than individual income. When family income increased
      in one minimum wage, the odds of using private providers increased by 20% while
      it was only 7% when there was a similar increase in individual income. Other
      variables had also a positive impact: female, age, schooling, and smaller family
      size. CONCLUSIONS: Elderly choices' on health care depend on the family's needs
      and resources and not on the individual's condition. Therefore, low-income
      elderly health is a lower priority in the family and it is disproportionately
      impaired by reduced family resources and deficiencies of public health care.

PMID- 14963551
TI  - [Impact of decentralization on health financing in Mexico].
AB  - OBJECTIVE: To identify trends and to describe the impact of health care
      decentralization on health financing policies in Mexico. METHODS: The study
      population comprised four states selected according with six technical criteria:
      socioeconomic development, implementation of decentralization process, database
      on economical features, data consistency and reliability, and technical support
      from a multidisciplinary team. In-depth interviews with key personnel as well as
      analysis of technical reports of state budgets for health in the period 1990-2000
      were conducted. RESULTS: The analysis model applied allowed to determine the
      trends and the impact of health care decentralization on main financing sources:
      householders, and federal, state and municipal governments. There was evidence of
      different change effectiveness, especially regarding trends of financing per
      source. CONCLUSIONS: There are states where householders and state and municipal
      governments effectively increased financing support for health care system. But
      there are also states where householders and state and municipal governments do
      not agree on the increase of financing support for health care system.

PMID- 14963552
TI  - [Psychoactive drug use in school age adolescents, Brazil].
AB  - To quantify psychoactive drug use and investigate use-related variables among
      students of Assis, Brazil, a questionnaire was administered to collect
      sociodemographic data and identify the pattern of non-medical use of psychoactive
      drugs in 20% of public and private school students. The largest consumption
      indexes for lifetime use were seen for alcohol (68.9%) and tobacco (22.7%). Drugs
      most often used were: solvents (10.0%); marijuana (6.6%); benzodiazepines (3.8%);
      amphetamines (2.6%); cocaine (1.6%); and anticholinergics (1.0%).

PMID- 14963553
TI  - [Mosquitoes with morning biting activity in the Atlantic forest, Brazil (Diptera,
      Culicidae)].
AB  - Previous studies on Culicidae in the state of Santa Catarina, Brazil, were
      limited to Anophelinae and Culex quinquefasciatus due to the past occurrence of
      malaria and filariasis but the mosquito fauna in forested areas is still almost
      unknown. It was carried out a survey of mosquitoes with morning biting activity
      in a tourist trekking trail of an Atlantic forest reserve area in the island of
      Santa Catarina. There were collected 358 specimens of 22 species, 14 of them
      reported for the first time in the state. Runchomyia reversa and Ochlerotatus
      scapularis were the predominant species. There was a great diversity of Wyeomyia
      (Phoniomyia) species.

PMID- 14963554
TI  - Aedes albopictus in an area of Misiones, Argentina.
AB  - Until early 1998 the presence of Aedes albopictus had never been detected in
      Argentina. During April of the same year, few individuals of this species were
      recorded in 33 breeding sites found in 25 out of 161 inspected houses in the city
      of Eldorado, Province of Misiones. The homogeneous spatial distribution of the
      proliferation foci suggests the existence of a generalized infestation in this
      locality during the study period.

PMID- 14963555
TI  - [Domestic water reservoir as breeding site of Aedes aegypti].

PMID- 14963556
TI  - [Data on hospital infection, external causes of death, and visceral leishmaniose
      in the state of Sao Paulo, Brazil].

PMID- 14963557
TI  - [Information on drug regulation and control of hospital infection].

PMID- 14963558
TI  - Abstracts of the 30th Annual Meeting on Basic Research in Chagas Disease and the
      XIX Meeting of the Brazilian Society of Protozoology. Caxambu, MG, Brasil. 10-12
      November 2003.

PMID- 14963570
TI  - [How to decide about not resuscitating very low birth weight infants in the
      delivery room?].

PMID- 14963571
TI  - [Treatment of unresectable non-small cell lung cancer: which is the best way for
      combining chemotherapy and radiotherapy?].

PMID- 14963572
TI  - [Vaginal endometriosis. How to do a surgical approach].

PMID- 14963574
TI  - [Should nuchal translucency be requested in prenatal care?].

PMID- 14963575
TI  - [Did the emerging of imaging methods allow for the early diagnosis of acute
      appendicitis in children?].

PMID- 14963582
TI  - [The measuring of quality of life].

PMID- 14963583
TI  - [Axillary breast in a man].

PMID- 14963584
TI  - [Cardiac risk in perioperative vascular procedures].

PMID- 14963586
TI  - [Evaluation of the nutritional status of children and adolescents with asthma].
AB  - OBJECTIVE: The aim of this study was to analyze the nutritional state of children
      and adolescents with asthma, and to relate this to patient age at the onset of
      disease, severity of the disease, family per capita income, and the level of
      maternal schooling. METHODS: A cross sectional study involved 66 patients from
      the Immunology, Allergy and Pulmonology outpatient clinic of the Hospital das
      Clinicas of the State University of Campinas (HC/UNICAMP). All of the patients
      suffered from atopic asthma and ranged in age from 4 to 14 years old. The
      patients were compared to 124 controls. RESULTS: There were no differences among
      male patients and the controls in the distribution of the z-scores for weight/age
      (p=0.24), height/age (p=0.61), body mass index (p=0.21), upper arm circumference
      (p=0.94) and triceps skinfold (p=0.49) in relation to disease severity, age at
      the first occurrence of disease, family per capita income, and the level of
      maternal schooling. Similarly, there were no significant differences in the z
      scores for weight/age (p=0.13), height/age (p=0.46), body mass index (p=0.13),
      upper arm circumference (p=0.06) among female patients and their controls.
      However, there was a difference (p=0.002) between the triceps skinfold of female
      patients (-0.74 +/- 0.84) and the controls (0.17 +/- 1.21). No child with asthma
      was obese (z-scores for body mass index > or =2). There were no significant
      differences in of the anthropometrical measurements among patients in relation to
      family per capita income, the level of maternal schooling, severity of the
      disease, and age at first occurrence the disease, but the mean weight of boys
      suffering from moderate asthma was lower than that of the other patients
      (p=0.02). CONCLUSIONS: The nutritional status of the patients studied was
      satisfactory so that their body composition was unaffected by the disease, on
      environment, or by any interaction between these two factors. Our results
      reinforce the view that an anthropometrical evaluation should be done
      periodically to assess the consequences of the disease and the impact of any
      interventions and therapeutic measures used. This will provide a better
      evaluation of the patient's overall health.

PMID- 14963587
TI  - [Informed consent in research: a new approach].
AB  - INTRODUCTION: The Informed Consent allows the person invited to participate of a
      research project to understand the procedures, risks, discomforts, benefits and
      rights involved; determining an autonomic decision. We want to verify in the
      informed consent process the adequacy of given information to research subjects
      in a collective way. METHODS: A research project was chosen from the gynecologic
      area. The collective obtainment consisted of an oral presentation. After that,
      The Consent form was shown. Forty-five patients were interviewed, immediately
      after the consent obtainment. RESULTS: Remembrance capacity of information about
      procedures, risks and benefits explained were verified. All participants (100%)
      remembered the procedures, 54% of them remembered the risks and 96% the probable
      benefits. Comparing these data with others from a similar study using
      conventional informed consent process (individual information transmission) the
      subjects remember more information in the present study. CONCLUSION: These
      results evidence the possibility to inform collectively the research subjects
      when getting the Informed Consent in those projects where this choice is
      available.

PMID- 14963588
TI  - [Translation and cultural adaptation of the quality of life assessment instrument
      for chronic renal patients (KDQOL-SF)].
AB  - BACKGROUND: The objective of this study was to translate from English into
      Portuguese and to perform cultural adaptation of the Kidney Disease Quality of
      Life Short Form--KDQOL-SF to make possible its validation in Brazil. METHODS:
      This instrument was translated from the original English version into Portuguese
      language by the authors and it was also translated by a certified translator and
      revised by a specialized translator who evaluated the level of difficulty for
      translation. Thirty end-stage renal disease patients undergoing dialysis were
      randomly selected to participate in the study. RESULTS: The mean age of patients
      was 47 +/- 9 years (23 to 60 yr), and the predominant education level was
      incomplete elementary school (1st to 8th grade=53%); 60% of the patients were
      female. The majority of patients (63%) were undergoing hemodialysis and the
      period of treatment within the last 30 days was 12 hours or more per week. The
      time of dialysis treatment was 0-2 years for 70% of the patients. The feasibility
      of the instrument and the difficulties found by the patients were evaluated by a
      panel of experts and changes were made regarding difficulties of comprehension.
      Some activities were substituted since they were not regular for the Brazilian
      population. There were modifications in expressions of translation for terms
      suggested by patients and Brazilian experts and, for five items it was suggested
      to include an explanation in parentheses. Common words used in the Portuguese
      language were chosen. CONCLUSIONS: The translation and cross-cultural adaptation
      of the KDQOL questionnaire to Portuguese were concluded, having been accomplished
      this important stage for its validation and use in our environment.

PMID- 14963589
TI  - [Bioethical study of kidney transplantation in Brazil involving unrelated living
      donors: the inefficiency of law to prevent organ commercialism].
AB  - OBJECTIVE: This study aimed to know the opinion of five different social segments
      (public prosecutors, judges, general population, recipients of the awaiting list
      for kidney transplants and the crew involved in the organ transplantation process
      of a hospital in Brasilia--Hospital de Base) about the present organ transplant
      legislation, with an emphasis on the donation of kidney by unrelated living
      donors, and the new determination given by Law #10.211, in March 23rd, 2001,
      specifically in its article 9, that enlarges the criteria for donation of organs
      between unrelated living people. METHODS: A questionnaire with six objective
      questions was used in order to know the opinion of five groups of people of the
      Federal District about the present organ transplant legislation in Brazil.
      RESULTS: For 80% of the people interviewed, when Brazilian legislation allows
      donation of organs between unrelated living people, it makes possible the
      existence of rewarded donation and 81% of them consider that the requirement for
      judicial authorization is not an effective instrument to prevent organ
      commercialism. CONCLUSIONS: The present research indicates that Brazilian
      legislation fails concerning the utilization of kidneys for transplantation from
      unrelated living donors, making possible the commerce of organs in the country.
      Considering that poor people are the most vulnerable ones in this context, the
      authors suggest changes in the legislation in force, aiming to protect them and,
      therefore, attain more justice.

PMID- 14963590
TI  - [Long term effect of hepatitis B and C virus infection on the survival of kidney
      transplant patients].
AB  - PURPOSE: To evaluate the impact of HCV (hepatitis C virus) and HBV (hepatitis B
      virus) infection on long-term graft and patient survival in renal
      transplantation. METHODS: One hundred and nine kidney allograft recipients were
      evaluated regarding the presence of antibodies against HCV and hepatitis B
      surface antigen. Patients were divided into four groups according to their
      serologic status and followed for ten years for survival analysis. Age, gender,
      renal failure etiology, length of previous dialysis and post transplantation
      periods were evaluated. RESULTS: Length on dialysis time was significantly longer
      in the anti-HCV positive group. There was also a higher number of patients with
      re-transplants in the HBV and HCV groups. There were no significant differences
      in 10-year patient survival in the anti-HCV positive group (71.0%; relative risk:
      1.13; CI: 0.86-1.47) and in the HBV infected group (77.8%; relative risk: 1.03;
      CI: 0.7-1.5) compared to the not infected group (80%). However, the group of
      patients infected with both viruses presented a significantly lower 10-year
      patient survival (37.5%; relative risk: 2.13; CI: 0.86-5.28) compared to the
      index group. There were no significant differences on graft survival among the
      groups. CONCLUSION: In the present study renal transplant patients infected
      concomitantly with HBV and HCV present a significantly lower long-term patient
      survival.

PMID- 14963591
TI  - [Prevalence of immunologic markers (Anti-GAD and Anti-IA2) in first-degree
      relatives of patients with type I diabetes in the greater area of Sao Paulo].
AB  - BACKGROUND: Increasingly accurate prediction of Type I Diabetes Mellitus (DMI),
      based on analysis of autoantibody markers, has become possible in first-degree
      relatives of patients with diabetes (PDMI). These markers indicate autoimmune
      process against pancreatic islet beta-cells. Anti-GAD and anti-IA2 are considered
      predictive of DMI, whose prevalences are considerably variable in different
      populations studied. There are few data about the frequency of these markers on
      the Brazilian population. The aim of this study is determine the prevalence of
      positivity for anti-GAD and for anti-IA2 among DMI patients first-degree
      relatives (PDMI) in a sample of the Brazilian population of Great Sao Paulo City.
      METHODS: Forty-eight children and adolescents PDMI with median of age of 14.5
      years (range 6.7 to 17.9 years). Anti-GAD and anti-IA2 was measured by radioassay
      (Kronus , USA). The cut-off limit for both antibodies was set at the 99th
      percentile from normal subjects serum samples (anti-GAD: n=194; Median of
      age=13.4 yrs; range 9.7 to 64 yrs; anti-IA2: n=71; Median of age=12.6; range 11.1
      15.2 yrs). A subject was considered to be positive for anti-IA2 if specific
      binding exceeded the 99th among the analysis of 71 subjects. The limit to
      positivity was 1.72 U/ml to anti-GAD and 0.97 U/ml to anti-IA2. RESULTS: Five
      PDMI (10.4%) have showed positivity to anti-GAD, with significantly higher
      prevalence than controls (P<0.01). The anti-IA2 prevalence rate seems to be
      equivalent between PDMI and controls. CONCLUSION: The prevalence of anti-GAD has
      been more prevalent among the PDMI. No differences were observed between
      prevalences for anti-IA2 showed by PDMI and controls.

PMID- 14963592
TI  - [Transvaginal electrical stimulation of the pelvic floor in the treatment of
      stress urinary incontinence: clinical and ultrasonographic assessment].
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of
      transvaginal electrical stimulation on the treatment of women with stress urinary
      incontinence (SUI) in selected cases. METHODS: Twenty two women with primary
      stress urinary incontinence diagnosed by urodynamic study were submitted to
      transvaginal electrical stimulation. The mean age was 49 years old (range 22 to
      74). The treatment consisted of two weekly sessions of stimulation, each 20
      minutes long, during 8 weeks. Women were evaluated through history, clinical and
      urogynecological exam, weekly registration of frequency of urinary leakage,
      stress test and transperineal ultrasound before and after treatment. A pulse of
      700 sec. was used, frequency of 50 Hz and intensity varying from 12 to 53 mA
      according to the women's sensitivity. RESULTS: Eighteen of 22 subjects (81.7%)
      were satisfied with electrical stimulation and frequency of urinary incontinence
      reduced significantly (p<0.01). Stress test was negative in 77.2% of the women
      after treatment. Valsalva leak-point pressure was higher in 14 (63.3%) women
      after treatment, although not reaching statistical significance (p=0.37). Bladder
      neck mobility did not change significantly before and after electrical
      stimulation (p=0.30). CONCLUSION: Transvaginal electrical stimulation of the
      pelvic floor is an effective and safe treatment to women with SUI without
      sphincter deficiency, with significant reduction of the frequency of urinary
      leakage.

PMID- 14963593
TI  - [Treatment of recurrent hemorrhage esophageal varices in schistosomotic patients
      after surgery].
AB  - OBJECTIVE: To standardize the treatment recurrent hemorrhage esophageal varices
      in schistosomotic patients after non decompressive surgery. METHODS: We treated
      45 patients with schistosomotic portal hypertension who presented recurrent
      hemorrhage esophageal varices. Performance of abdominal ultrasonography and
      arteriographic studies and two groups were defined: Group A: Nineteen patients
      (42.2%) with absence of spleen, occluded splenic artery and patency of left
      gastric artery and vein, thus characterizing splenectomy at prior operation.
      Group B: Twenty six patients (57.8%) with absence of spleen image, occluded
      splenic and left gastric artery and non-opacified left gastric vein, showing
      splenectomy and some type of gastroesophageal devascularization performed before.
      Patients of Group A were reoperated to carry out the gastroesophageal
      devascularization and patients of Group B were submitted to a sclerotherapy
      program. RESULTS: In Group A, one patient (5.3%) presented recurrent hemorrhage
      on the late postoperative period. The esophageal varices decreased in number or
      diameter in 14 patients (73.7%), disappeared in three (15.8%) and remained
      unchanged in two (10.5%), under final endoscopic evaluation. In Group B, six
      patients (23.1%) presented recurrent bleeding. In four patients the acute
      hemorrhagic event were controlled. Two patients who underwent mesocaval shunt
      owing to unsuccess of these methods died postoperatively. Esophageal varices
      disappeared in 17 patients (65.4%), decreased in number or diameter in seven
      (26.9%) and remained unchanged in two (7.7%) after the last endoscopic
      evaluation. CONCLUSIONS: 1) The gastroesophageal devascularization is
      appropriated to splenectomized patients, with patency of left gastric artery and
      vein. 2) A long term of esophageal varices endoscopic sclerotherapy may be an
      option to splenectomized patients, with occluded left gastric artery and non
      opacified left gastric vein.

PMID- 14963594
TI  - [Sexual function in males undergoing liver transplantation].
AB  - BACKGROUND: Sexual dysfunction is very common in liver transplantation
      candidates. Our objective is to determine the sexual life quality of males before
      and after liver transplantation. METHODS: Questionnaire was sent to 56 males over
      18 years of age with at least six-month survival after orthotopic liver
      transplantation. The self-administered questionnaire contained 15 questions with
      5 or 6 alternatives to determine the male sexual function which may be divided
      into 5 domains: 1) erectile function; 2) orgasmic function; 3) sexual desire; 4)
      intercourse satisfaction; and 5) overall satisfaction with sexual life. Each
      answer received a score. Domains scores were computed by summing the scores for
      individual answers and they were compared before and after the liver
      transplantation. RESULTS: Twenty-five patients answered the questionnaire
      completely. All 5 sexual function domains improved after liver transplantation.
      The score of the erectile function increased from 21.12 +/- 8.07 to 26.52 +/-
      5.22 (p=0.004), of the orgasmic function from 7.28 +/- 3.05 to 9.36 +/- 1.47
      (p=0.008), of the sexual desire from 6.64 +/- 2.58 to 8.68 +/- 1.35 (p=0.005), of
      intercourse satisfaction from 9.16 +/- 3.83 to 12.52 +/- 2.65 (p<0.0001) and of
      overall satisfaction from 7.12 +/- 2.64 to 9.24 +/- 1.65 (p=0.002). CONCLUSIONS:
      Sexual dysfunction is common in males with severe chronic liver disease and liver
      transplantation improves all sexual function domains: erectile function, orgasmic
      function, sexual desire, intercourse satisfaction and overall satisfaction.

PMID- 14963595
TI  - [Sex hormones profile in women on dialysis program in treatment with
      erythropoietin].
AB  - OBJECTIVE: The end stage renal disease has accompaniments in body systems,
      including hormonal changes. The present study was designed to evaluate the
      pattern of follicle stimulating hormone (FSH), luteinizing hormone (LH),
      prolactin (PRL) and estradiol (E2) in 47 women with end stage renal disease
      (ESRD), on regular dialysis and receiving recombinant human erythropoietin (r
      HuEPO). METHODS: One patient was on intermittent peritoneal dialysis, 4 on
      continuous ambulatory peritoneal dialysis and 42 on maintenance haemodialysis.
      They were divided into: Group I consisted of 10 women with regular menses, aged
      lesser than 48 years; Group II consisted of 15 women with amenorrhea, aged lesser
      than 48 years and; Group III, consisted of 22 women with amenorrhea, aged 48
      years or more. Levels of FSH, LH, PRL and E2 were obtained by ELISA. RESULTS: All
      groups showed FSH, LH and E2 levels in the normal range for normal women without
      renal failure, and there was no statistical significance in the levels of these
      hormones between women with regular menses or women with amenorrhea aged lesser
      than 48 years. The serum concentrations of PRL were above the normal range in all
      groups. The patients aged 48 or more showed hormonal profile consistent with post
      menopausal (i.e. high FSH, high LH and low estradiol). CONCLUSIONS: We conclude
      that ovarian function is intact on ESRD and we have to search for other causes
      for amenorrhea in women that do not have an abnormal hormonal sex profile.

PMID- 14963596
TI  - [Evaluation of the nutritional status and physical performance in candidates to
      liver transplantation].
AB  - OBJECTIVE: To evaluate the physical capacity and nutritional status of patients
      before orthotopic liver transplantation (OLT) and to correlate these parameters
      to the severity of liver function. METHODS: Thirty-two patients before OTL were
      classified as Child-Pugh A (25%), B (22%) and C (53%). Physical capacity was
      analyzed by the quadriceps and ankle strength, balance, coordination, gait
      velocity, 6 minute walk test, get up and go test, Barthel and Karnofsky indexes.
      Nutritional status was evaluated by using Mendenhall score and Blackburn
      classification. RESULTS: Quadriceps weakness was found in 32% of the patients.
      Impaired balance and coordination were detected in 34.8% and 15.6% of the
      patients. Low physical performance was found in 72.5% of the patients (6 min walk
      test: 31.6% severely; 40.9% moderately impaired) and 43.8% required considerable
      assistance when the Karnofsky index was applied. Malnutrition was found in 62.5%
      of the patients (34.37% moderately and severely malnourished and 28.13% mildly
      malnourished). Chi-square analysis showed no association between Child-Pugh
      classification and nutritional status, the 6 min walk test and Karnofsky index.
      The association between the two functional tests was statistically significant
      (p<0.001). CONCLUSION: The results show that physical impairment and nutritional
      deficit were highly prevalent in the patients studied, independent of the degree
      of hepatic dysfunction evaluated by the traditional Child-Pugh classification.

PMID- 14963597
TI  - [Body mass index, pubertal development and their relationship with menarche].
AB  - OBJECTIVE: Age of menarche, nutritional status and the pubertal development were
      studied in a sample of low economic level adolescents. METHODS: Retrospective
      study, collecting data from the register charts of 229 adolescents between 10 and
      18.8 years of age, attended at primary level of public institution. Were
      collected: chronological age, age of menarche, body weight and height (from which
      the body mass index was calculated), and Tanner's pubertal stage for breast
      development. Register charts of adolescents with pathological conditions
      compromising the occurrence of menarche were not taken into consideration. Two
      groups were formed, with and without the occurrence of menarche. RESULTS: The
      mean chronological age (p<0.001) and the body mass index (p<0.001) were greater
      in the group with menarche. The occurrence of menarche was at 12.1 +/- 1.1 years.
      There was significant difference between groups in relation to breast
      development, being the n of the group with menarche greater in M4 + M5 stages
      (p<0.001), and the group without menarche greater in M1 (p<0.001) and M2
      (p<0.001) stages. An overweight (p<0.001) and obesity (p<0.001) relationship with
      the group with menarche was observed, and a relationship of undernutrition
      (p<0.001) and eutrophy (p<0.001) with the groups without menarche. CONCLUSIONS:
      An attentive follow-up of weight and height of adolescents before menarche,
      before the menarche period, in relatively precocious pubertal stages, is
      necessary to allow attitudes to prevent and control disorders such as obesity.

PMID- 14963598
TI  - [IgA, IgE and IgG subclasses to Candida albicans in serum and vaginal fluid from
      patients with vulvovaginal candidiasis].
AB  - PURPOSE: To determine the levels of IgA, IgE, IgG and subclasses (IgG1, IgG4)
      antibodies specific to C. albicans in serum and vaginal washes from women with or
      without vulvovaginal candidiasis in order to evaluate the role of these
      antibodies in the immunopathogenesis of the disease. METHODS: Thirty women with
      clinical symptoms of vulvovaginal candidiasis (15 positive vaginal culture to C.
      albicans, 11 negative culture and 4 positive culture to non-C. albicans) and 12
      asymptomatic control women were selected. Serum and vaginal wash samples were
      obtained for the detection of anti-C. albicans antibodies by ELISA. RESULTS:
      Symptomatic patients with positive culture showed significantly higher levels of
      specific IgA in vaginal washes and lower in serum than those with negative
      culture. Specific serum IgE levels were very low compared to vaginal IgE. High
      levels of total specific IgG were found in serum and vaginal washes in both
      groups, regardless the fungal presence or absence. Specific IgG1 and IgG4 levels
      were significantly higher only in vaginal washes from symptomatic patients with
      positive culture, with a slightly higher IgG1/IgG4 ratio, indicating that the
      IgG1 antibody response may be predominantly involved in the fungal clearance.
      CONCLUSION: Our results indicate a pronounced antibody response of IgA, IgG1 and
      IgG4 to C. albicans in vaginal washes in symptomatic patients with positive
      culture, suggesting a important role of these antibodies in the local immune
      response triggered by the presence of the fungus.

PMID- 14963599
TI  - [Risky behavior for traffic accidents: a survey among medical students in
      Southern Brazil].
AB  - BACKGROUND: Traffic accidents are one of the most frequent cause of mortality
      among Brazilian youths. Therefore, this study aimed at detecting the prevalence
      of risk factors for such accidents in a young population. METHODS: Questionnaires
      containing questions about risky behavior for traffic accidents were answered by
      students from the first to the fourth year of the Medical course of the State
      University of Londrina, Parana State, Brazil, during October and November, 2000.
      The chi-square test was used to detect differences between the sexes, with a 5%
      significance level. RESULTS: Compared to women, male students reported a
      statistically significant higher frequency of transportation as a car driver,
      owning a driver license, to have learnt to drive a car under the age of 16 and to
      have drunk alcoholic beverages before driving a vehicle during the last 30 days.
      Among regular drivers, a lower proportion of desirable behavior was also noted
      among male students. Lack of attention (59.3%), disregarding traffic signals
      (33.5%) and speeding (22.5%) were the main factors cited as determinants for the
      occurrence of the last accident, with no gender difference. CONCLUSIONS: These
      results point out for the need to implement measures in order to reduce factors
      that favors the occurrence of traffic accidents among these youths, especially
      among males.

PMID- 14963600
TI  - [Evidence based clinical practice. Part 1--well structured clinical questions].
AB  - Clinical decisions in daily practice, to resolve patient's problem, are usually
      based at the conscious use of the available information, through explicit
      determined rules. Evidence based clinical practice recognize the explicit and
      tacit knowledge, understanding that it is impossible all the aspects of
      professional competence become explicit. The doubt becomes part of the decision
      process, identifying initially the unconscious component involved and after the
      explicit knowledge used. When we make a structured clinical question with a
      possible answer, it is necessary to remember that the doubt can be related to
      basics and of definition aspects of the disease or related to the patient's
      manager, like diagnose, treatment and prognosis. Along our medical life, both
      types of question are present, with proportional change as the experience
      increase along the clinical practice. The process to find an appropriate answer
      to the doubt, came out at patient's care, depends on how the parts of this
      process will be structured. The recommended form is known by PICO abbreviation,
      that means: P: patient or population, I: intervention or indicator, C: comparison
      or control and O: outcome, or the answer expected found at the scientific
      information bases. This is the first basic need to a successful search, and the
      second need is to find the key words that better describe each of the four
      components of the questions. Without this caution, the search at compute
      databases results in absence of information or in a lot of information that it is
      not related to our interest.

PMID- 14963601
TI  - [Poststroke depression: risk factors and antidepressant treatment].
AB  - Depression is the most frequent psychiatric complication among stroke survivors.
      Several aspects have been indicated as risk factors for its occurrence. This
      review investigates the risk factors and the state of the art of the treatment
      for poststroke depression, in order to stimulate its detection and adequate
      treatment by the physician. The point prevalence of Major Depression after stroke
      varies from 10% to 34%, varying according to differences among the research
      methods. The length of poststroke period, characteristics of the sample, type of
      treatment received by patients and diagnostic criteria used can influence the
      reported prevalence of poststroke depression. The risk factors that have been
      associated with the occurrence of poststroke depression, are: functional and
      cognitive impairment, previous history of depression and stroke, sex, age,
      hypercortisolism, poor social support and stroke neuroanatomic correlates. This
      one has supported the formulation of a pathophysiological mechanism for
      poststroke depression related with prefrontosubcortical circuits and
      neurotransmission of biogenic amines. The depression has a harmful impact on
      stroke prognosis. It can cause a more severe functional impairment, retardation
      of the rehabilitation process, outcome complications, and a higher mortality
      risk. In addition, poststroke depression has not been accurately diagnosed and
      treated. With the advantage of the magnetic resonance, researchers should focus
      investigations on the association of specific cerebral regions with the
      depressive manifestation and treatment response. Methodological issues such as
      previous history of depression and the type of the depressive manifestation
      should be considered for analysis.

PMID- 14963602
TI  - [Standardization of equipment and techniques for conducting echocardiographic
      examinations].

PMID- 14963603
TI  - [Guideline for indication and utilization of echocardiography in clinical
      practice].

PMID- 14963604
TI  - Frequency of hypertension in chronic Chagas' disease: retrospective clinical
      study.
AB  - OBJECTIVE: To assess the frequency of hypertension in chagasic patients, as well
      as its clinical behavior and cardiologic findings. METHODS: We carried out a
      retrospective study with 225 patients with chronic Chagas' disease and
      hypertension (104 males), mean age of 55.1   11.8. These patients were being
      followed up in the outpatient care clinics from 1984 to 2000. The study assessed
      the clinical, electrocardiographic, and radiological viewpoints. RESULTS: Of the
      225 hypertensive patients (prevalence = 33.3%), 78 (34.7%) had mild hypertension,
      108 (48%) had moderate hypertension, and 39 (17.3%) had severe hypertension. The
      association of left anterosuperior divisional block and right bundle-branch block
      occurred in 39 cases (17.3%), and enlargement of the cardiac area on radiological
      examination occurred in 93 (44.9%) of the 207 cases studied. The undetermined
      form of Chagas' disease was the most prevalent, 30.2% of the cases, followed by
      the form associated with conduction disorders in 27.1%, and the isolated form of
      conduction disorders in 21.3%. CONCLUSION: Chagasic patients had a frequency of
      hypertension similar to that of the general population, and the clinical profile
      of the hypertensive chagasic patients seemed not to differ a lot from that of the
      chagasic patients.

PMID- 14963605
TI  - Quantifying the risk of coronary artery disease in a community: the Bambui
      project.
AB  - OBJECTIVE: To determine the coronary risk profile in adults and elderly in a
      community. METHODS: The study comprised a sample of adults (30-59 years, n=547)
      and the entire elderly population (60-74 years, n=1165) residing in Bambui town,
      Brazil. The Framingham score based on sex, age, smoking, diabetes mellitus,
      systolic and diastolic blood pressure, total cholesterol, and HDL-C was used. The
      score based on age and sex was defined as "expected" and compared with the mean
      score obtained by the sum of all risk factors in each age group and sex (score
      "observed"). RESULTS: The difference between the scores "observed" and "expected"
      increased with aging in both sexes. Smoking increased the difference from 30
      years of age onwards, in both sexes, and hypertension was important in men above
      the age of 30 years and in women above the age of 50 years. Diabetes and elevated
      total cholesterol increased the risk of the disease above the age of 50 years in
      both sexes. A higher level of HDL-C reduced the risk among men above the age of
      30 years, with no significant difference among women. Less schooling (< 4 years
      versus > or = 4 years) was associated with a higher score in adults of both
      sexes, but not among the elderly. CONCLUSION: Based on these results, in the
      community studied, the risk of coronary artery disease may be reduced up to 44%
      in men and 38% in women.

PMID- 14963606
TI  - Follow-up study of morphology and cardiac function in rats undergoing induction
      of supravalvular aortic stenosis.
AB  - OBJECTIVE: To characterize the follow-up of an experimental model of left
      ventricular hypertrophy (LVH) induced by supravalvular ascending aortic stenosis
      in young rats. METHODS: Wistar rats were submitted to thoracotomy and aortic
      stenosis was created by placing a clip on the ascending aorta (AoS group, n=12).
      Age-matched control animals underwent a sham operation (C group, n=12). Cardiac
      function was analysed by echocardiograms performed 6, 12, and 21 weeks after
      aortic banding. Myocardial morphological features and myocardial hydroxyproline
      concentration (HOP) were evaluated 2, 6, 12, and 21 weeks after surgery in
      additional animals. RESULTS: Aortic banding promoted early concentric LVH and a
      progressive increase in HOP. Under light microscopy, we observed myocyte
      hypertrophy and wall thickening of the intramural branches of the coronary
      arteries due to medial hypertrophy. Cardiac function was supranormal after 6
      weeks (percentage of fractional shortening - EAo6: 70.3 +/- 10.8; C6: 61.3 +/-
      5.4; p<0.05), and depressed in the last period. Diastolic dysfunction was
      detected after 12 weeks (ratio of early-to-late filling velocity - EAo12: 4.20 +/
      3.25; C12: 1.61 +/- 0.16; p<0.05). CONCLUSION: Ascending aortic stenosis
      promotes concentric LVH with myocardial fibrosis and minimal histological
      changes. According to the period of evaluation, cardiac function may be improved,
      normal, or depressed. The model is suitable and useful for studies on
      pathophysiology and treatment of the different phases of cardiac hypertrophy.

PMID- 14963607
TI  - Influence of skeletal muscle mass on ventilatory and hemodynamic variables during
      exercise in patients with chronic heart failure.
AB  - OBJECTIVE: To assess the influence of skeletal muscle mass on ventilatory and
      hemodynamic variables during exercise in patients with chronic heart failure
      (CHF). METHODS: Twenty-five male patients underwent maximum cardiopulmonary
      exercise testing on a treadmill with a ramp protocol and measurement of the
      skeletal muscle mass of their thighs by using magnetic resonance imaging. The
      clinically stable, noncachectic patients were assessed and compared with 14
      healthy individuals (S) paired by age and body mass index, who underwent the same
      examinations. RESULTS: Similar values of skeletal muscle mass were found in both
      groups (CHF group: 3863   874 g; S group: 3743   540 g; p = 0.32). Significant
      correlations of oxygen consumption in the anaerobic threshold (CHF: r = 0.39; P=
      0.02 and S: r = 0.14; P = 0.31) and of oxygen pulse also in the anaerobic
      threshold (CHF: r = 0.49; P = 0.01 and S: r =0.12; P = 0.36) were found only in
      the group of patients with chronic heart failure. CONCLUSION: The results
      obtained indicate that skeletal muscle mass may influence the capacity of
      patients with CHF to withstand submaximal effort, due to limitations in their
      physical condition, even maintaining a value similar to that of healthy
      individuals. This suggests qualitative changes in the musculature.

PMID- 14963608
TI  - Comparative study of smokers, ex-smokers, and nonsmokers who have experienced
      myocardial infarction.
AB  - OBJECTIVE: To assess the impact of smoking on in-hospital morbidity and mortality
      in patients who have experienced acute myocardial infarction and to assess the
      association between smoking and other cardiovascular risk factors and clinical
      data. METHODS: A prospective cohort study analyzed 121 patients, including 54
      smokers, 35 ex-smokers, and 32 nonsmokers. RESULTS: Using the chi-square test
      (P<0.05), an association between smoking and the risk factors sex, age, and
      diabetes was documented. Among the morbidity and mortality variables, only acute
      pulmonary edema showed a statistically significant difference (OR=9.5; 95% CI),
      which was greater in the ex-smoker group than in the nonsmoker group. CONCLUSION:
      An association between smoking and some cardiovascular risk factors was observed,
      but no statistical difference in morbidity and mortality was observed in the
      groups studied, except for the variable acute pulmonary edema.

PMID- 14963609
TI  - Lipid profile and cardiovascular risk in two Amazonian populations.
AB  - OBJECTIVE: To compare the lipid profiles and coronary heart disease risks of 2
      Brazilian Amazonian populations as follows: a riverside population (village of
      Vigia) and an urban population (city of Bel m in the state of Par ). METHODS:
      Fifty individuals controlled for age and sex were assessed in each region, and
      the major risk factors for coronary heart disease were analyzed. RESULTS:
      According to the National Cholesterol Education Program (NCEP III) and using the
      Framingham score, both populations had the same absolute risk of events (Vigia =
      5.4 +/- 1 vs Bel m = 5.7 +/- 1), although the population of Vigia had a lower
      consumption of saturated fat (P<0.0001), a greater consumption of mono- and
      polyunsaturated fat (P<0.03), in addition to lower values for body mass index
      (25.4 +/- 0.6 vs 27.6 +/- 0.7 kg/m , P<0.02), of biceps skin fold (18.6 1.1 vs
      27.5 +/- 1.3 mm, P<0.0001), of triceps skin fold (28.7 +/- 1.2 vs 37.3 +/- 1.7
      mm, P<0.002), and of total cholesterol (205 +/- 5 vs 223 +/- 6 mg/dL, P< 0.03)
      and triglycerides (119 +/- 9 vs 177 +/- 18 mg/dL, P<0.005). Both populations did
      not differ in regard to HDL-C (46 +/- 1 vs 46 +/- 1 mg/dL), LDL-C (135 +/- 4 vs
      144 +/- 5 mg/dL) and blood pressure (SBP 124 +/- 3 vs 128 +/- 3 mmHg; DBP 80 +/-
      2 vs 82 +/- 2 mmHg). CONCLUSION: The riverside and urban populations of Amazonia
      had similar cardiovascular risks. However, the marked difference in the variables
      studied suggests that different strategies of prevention should be applied.

PMID- 14963610
TI  - Pulmonary vein pulsatility in fetuses of diabetic mothers: prenatal Doppler
      echocardiographic study.
AB  - OBJECTIVE: To verify the hypothesis that the pulmonary vein pulsatility index is
      higher in fetuses of diabetic mothers than it is in normal fetuses of nondiabetic
      mothers. METHODS: Twenty-four fetuses of mothers with either gestational or
      previous diabetes (cases), and 25 normal fetuses of mothers without systemic
      disease (control) were examined. Fetuses were examined through prenatal Doppler
      and color flow mapping. The pulmonary vein pulsatility index was obtained by
      placing the pulsed Doppler sample volume over the right superior pulmonary vein
      and applying the formula (systolic velocity - presystolic velocity)/mean
      velocity. RESULTS: The mean gestational age of the study fetuses was 30.3 2.7
      weeks, and gestational age of the controls was 29 3.3 weeks, with no significant
      difference in gestational age between groups (p=0.14). Fetuses of diabetic
      mothers had a mean pulmonary vein pulsatility index of 1.6 1, and those of the
      control group had an index of 0.86 0.27. CONCLUSION: Fetuses of diabetic mothers
      had pulmonary vein pulsatility indexes (parameter easily obtained through Doppler
      echocardiography that may be related to fetal diastolic function) higher than
      those in fetuses of mothers with normal glycemia.

PMID- 14963611
TI  - Spontaneous rupture of a right atrial angiosarcoma and cardiac tamponade.
AB  - Primary cardiac angiosarcoma is a rare disease of difficult diagnosis and poor
      prognosis frequently associated with recurring hemopericardium. We report the
      case of a 30-year-old female with a right atrial angiosarcoma and spontaneous
      rupture to the pericardial cavity, who was diagnosed during an emergency
      exploratory thoracotomy, whose indication was cardiac tamponade. This is the 8th
      case reported in the literature. Clinical findings are discussed and a literature
      review is provided.

PMID- 14963612
TI  - [Anatomo-clinical correlation. Case 6/2003 - A 61-year-old man with progressive
      and refractory cardiac insufficiency, myocardial infarction, coronary
      atherosclerosis and myocardial bridging].

PMID- 14963613
TI  - [Clinical and radiological correlation. Case 12/2003 - Instituto do Coracao do
      Hospital das Clinicas da FMUSP ].

PMID- 14963614
TI  - Biotechnological advantages of laboratory-scale solid-state fermentation with
      fungi.
AB  - Despite the increasing number of publications dealing with solid-state
      (substrate) fermentation (SSF) it is very difficult to draw general conclusion
      from the data presented. This is due to the lack of proper standardisation that
      would allow objective comparison with other processes. Research work has so far
      focused on the general applicability of SSF for the production of enzymes,
      metabolites and spores, in that many different solid substrates (agricultural
      waste) have been combined with many different fungi and the productivity of each
      fermentation reported. On a gram bench-scale SSF appears to be superior to
      submerged fermentation technology (SmF) in several aspects. However, SSF up
      scaling, necessary for use on an industrial scale, raises severe engineering
      problems due to the build-up of temperature, pH, O2, substrate and moisture
      gradients. Hence, most published reviews also focus on progress towards
      industrial engineering. The role of the physiological and genetic properties of
      the microorganisms used during growth on solid substrates compared with aqueous
      solutions has so far been all but neglected, despite the fact that it may be the
      microbiology that makes SSF advantageous against the SmF biotechnology. This
      review will focus on research work allowing comparison of the specific biological
      particulars of enzyme, metabolite and/or spore production in SSF and in SmF. In
      these respects, SSF appears to possess several biotechnological advantages,
      though at present on a laboratory scale only, such as higher fermentation
      productivity, higher end-concentration of products, higher product stability,
      lower catabolic repression, cultivation of microorganisms specialized for water
      insoluble substrates or mixed cultivation of various fungi, and last but not
      least, lower demand on sterility due to the low water activity used in SSF.

PMID- 14963615
TI  - An enzymatic assay for metabolites of perfluoro-tagged 5-hydroxytryptophan.
AB  - l-5-hydroxytryptophan (5-HTP) with two types of multiple (19)F-atom tags bonded
      at various positions onto the indole ring (positions 4, 6, or 7) was exposed to
      aromatic l-amino acid decarboxylase (AADC) in lysates of Escherichia coli JM109
      which had been transformed with the plasmid pKKAADCII. Resulting samples were
      analyzed with HPLC. In the first study, which investigated a straight-chain seven
      atom tag, a novel peak, putatively perfluoro-tagged serotonin, was detected. A
      second study demonstrated that 5-HTP was converted to 5-HT in transformed E.coli
      lysate but not in untransformed lysate. A third study, investigating a tag with
      nine fluorine atoms all in the same nuclear environment, identified the isomer
      serving as the best substrate for AADC. This novel molecule had the tag bonded at
      the 6 position on the indole ring. Isomers that fit into the active site of AADC
      are likely to follow the biosynthetic path for serotonin in vivo and are
      potentially useful in (19)F magnetic resonance spectroscopy studies. The
      enzymatic assay described here provides an efficient and cost-effective tool for
      screening new compounds.

PMID- 14963616
TI  - Effect of ppc gene knockout on the metabolism of Escherichia coli in view of gene
      expressions, enzyme activities and intracellular metabolite concentrations.
AB  - Physiological characteristics and regulatory mechanism were investigated based on
      comparative analyses of gene expressions, enzyme activities and intracellular
      metabolite concentrations between the ppc knockout Escherichia coli strain
      JWK3928 and its parent strain BW25113. RT-PCR was used to detect gene expressions
      in both strains. It was observed that the ppc knockout strain excreted little
      acetate and produced less carbon dioxide at the expense of a slower growth rate
      together with a lower glucose consumption rate, as compared with the parent
      strain. Accordingly, the biomass yield on glucose was improved in the ppc(-)
      mutant. It was found that genes such as gltA, icd, aceA and mdh involved in the
      glyoxylate shunt and part of the tricarboxylic acid cycle were significantly
      upregulated, whereas genes involved in glycolysis and the pentose phosphate
      pathway, such as pgi, fba, gapA, zwf and gnd, were significantly downregulated in
      response to ppc knockout. It was also found that the intracellular metabolites in
      glycolysis and the pentose phosphate pathway, such as phosphoenolpyruvate,
      glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-phosphate and 6
      phosphogluconate, increased, whereas oxaloacetate and acetyl-CoA concentrations
      decreased in ppc(-) mutant, as compared with those in the parent strain.
      Comparison between the gene expressions and enzyme activities implies that most
      of them were well correlated, except a few genes such as icd. It can be said from
      the present investigation that the combination of the information from gene
      expressions, enzyme activities and intracellular metabolite concentrations
      provides a comprehensive understanding of the physiological consequences and
      regulatory mechanisms for the specific gene-knockout E. coli.

PMID- 14963617
TI  - Evaluation of agar diffusion bioassay for nisin quantification.
AB  - The agar diffusion bioassay is the most widely used method for the quantification
      of nisin, due to its high sensitivity, simplicity, and cost-effectiveness. This
      method is based on the measurement of the inhibition zone produced in nisin
      sensitive microorganisms. The size of the zone is affected by many factors, such
      as nisin-sensitive strain, amount of added agar and surfactant, and pre-diffusion
      step. This research aims to evaluate the effects of nisin-sensitive strains and
      pre-diffusion on the accuracy and precision of nisin quantification. Three
      strains of nisin-sensitive microorganisms (Micrococcus luteus, Lactobacillus
      sakei, Brochothrix thermosphacta) were tested along with three different
      incubation processes. The best combination was the method using L. sakei as an
      indicator strain with pre-diffusion at 4 degrees C for 24 h. Compared with M.
      luteus and B. thermosphacta, L. sakei gave more accurate and reproducible
      results. Moreover, the pre-diffusion step resulted in larger inhibition zones and
      more precise results. Finally, the best combination was validated and compared
      with the method that is usually used and the result showed that the method using
      L. sakei with pre-diffusion gave more accurate and precise results.

PMID- 14963618
TI  - Definition of supertypes for HLA molecules using clustering of specificity
      matrices.
AB  - Major histocompatibility complex (MHC) proteins are encoded by extremely
      polymorphic genes and play a crucial role in immunity. However, not all
      genetically different MHC molecules are functionally different. Sette and Sidney
      (1999) have defined nine HLA class I supertypes and showed that with only nine
      main functional binding specificities it is possible to cover the binding
      properties of almost all known HLA class I molecules. Here we present a
      comprehensive study of the functional relationship between all HLA molecules with
      known specificities in a uniform and automated way. We have developed a novel
      method for clustering sequence motifs. We construct hidden Markov models for HLA
      class I molecules using a Gibbs sampling procedure and use the similarities among
      these to define clusters of specificities. These clusters are extensions of the
      previously suggested ones. We suggest splitting some of the alleles in the A1
      supertype into a new A26 supertype, and some of the alleles in the B27 supertype
      into a new B39 supertype. Furthermore the B8 alleles may define their own
      supertype. We also use the published specificities for a number of HLA-DR types
      to define clusters with similar specificities. We report that the previously
      observed specificities of these class II molecules can be clustered into nine
      classes, which only partly correspond to the serological classification. We show
      that classification of HLA molecules may be done in a uniform and automated way.
      The definition of clusters allows for selection of representative HLA molecules
      that can cover the HLA specificity space better. This makes it possible to target
      most of the known HLA alleles with known specificities using only a few peptides,
      and may be used in construction of vaccines. Supplementary material is available
      at http://www.cbs.dtu.dk/researchgroups/immunology/supertypes.html.

PMID- 14963619
TI  - Diversity of Mhc class I and IIB genes in house sparrows (Passer domesticus).
AB  - In order to understand the expression and evolution of host resistance to
      pathogens, we need to examine the links between genetic variability at the major
      histocompatibility complex ( Mhc), phenotypic expression of the immune response
      and parasite resistance in natural populations. To do so, we characterized the
      Mhc class I and IIB genes of house sparrows with the goal of designing a PCR
      based genotyping method for the Mhc genes using denaturing gradient gel
      electrophoresis (DGGE). The incredible success of house sparrows in colonizing
      habitats worldwide allows us to assess the importance of the variability of Mhc
      genes in the face of various pathogenic pressures. Isolation and sequencing of
      Mhc class I and IIB alleles revealed that house sparrows have fewer loci and
      fewer alleles than great reed warblers. In addition, the Mhc class I genes
      divided in two distinct lineages with different levels of polymorphism, possibly
      indicating different functional roles for each gene family. This organization is
      reminiscent of the chicken B complex and Rfp-Y system. The house sparrow Mhc
      hence appears to be intermediate between the great reed warbler and the chicken
      Mhc, both in terms of numbers of alleles and existence of within-class lineages.
      We specifically amplified one Mhc class I gene family and ran the PCR products on
      DGGE gels. The individuals screened displayed between one and ten DGGE bands,
      indicating that this method can be used in future studies to explore the
      ecological impacts of Mhc diversity.

PMID- 14963620
TI  - Sequence of beta(2)-microglobulin from rhesus macaque ( Macaca mulatta) includes
      an allelic variation in the 3'-untranslated region.
AB  - The rhesus macaque ( Macaca mulatta) has become a popular animal model for
      several human infectious diseases, such as HIV (modeled by SIV infection),
      hepatitis, and malaria. Investigation of T-cell responses in experimental
      infectious diseases in rhesus macaques has benefited from an expanding
      understanding of the diversity of macaque MHC class I heavy chains and the
      restriction of antigen presentation by macaque class I molecules. Here we add to
      this understanding with the first nucleotide sequences of M. mulatta beta(2)
      microglobulin (beta(2)m) mRNA, including a portion of the 3'-untranslated region
      (3'UTR). In pairwise comparison, the beta(2)m protein of M. mulatta differs from
      human and chimpanzee beta(2)m by nine amino-acid substitutions (92% identity),
      and from Macaca fascicularis by one amino-acid difference in the signal peptide
      region (99% identity). Allelic variations were identified at one site in the
      3'UTR. A structural analysis of human or chimpanzee beta(2)m and M. mulatta
      beta(2)m suggests that the differences cluster in three solvent-exposed clusters
      and do not involve contacts with the class I heavy chain. We predict that human
      and macaque beta(2)m should bind interchangeably with the class I heavy chains of
      the other species, and show that four M. mulatta class I alleles form cell
      surface complexes with human beta(2)m. Further, we predict that W6/32 (a
      monoclonal antibody that recognizes a combined epitope of some class I heavy
      chains and beta(2)m with a subtle species dependence) should bind similarly human
      or macaque class I molecules that are bound with beta(2)m of either species,
      supported by evidence of recognition of both heterologous and homologous
      complexes of macaque class I heavy chains. Our findings contribute to the growing
      understanding of rhesus macaque histocompatibility antigens and antigen
      presentation, and to the phylogeny of beta(2)m in primates.

PMID- 14963622
TI  - Bone-mineral density deficits from childhood cancer and its therapy. A review of
      at-risk patient cohorts and available imaging methods.
AB  - The growing population of childhood cancer survivors--currently estimated at 1 in
      900 young adults aged 15-45 years--underscores the importance of studying long
      term complications of oncotherapy. While these patients are returning to the
      mainstream of life, they carry with them toxicities from prior therapy that may
      compound or potentiate changes typically seen with the normal aging process.
      Skeletal toxicities such as scoliosis, craniofacial dysplasia, and limb-length
      discrepancy are readily apparent. However, others such as osteoporosis and
      osteonecrosis are silent until they reach advanced stages when attempts at
      amelioration may be unsuccessful. This review addresses bone-mineral density
      deficits that may predispose childhood cancer survivors to earlier onset and more
      severe osteopenia and osteoporosis than the normal population.

PMID- 14963623
TI  - Determination of fifteen priority phenolic compounds in environmental samples
      from Andalusia (Spain) by liquid chromatography-mass spectrometry.
AB  - This work describes the optimisation of a method to determinate fifteen phenolic
      compounds in waters, sediments and biota (green marine algae) by liquid
      chromatography coupled to mass spectrometry (LC-MS) with atmospheric pressure
      chemical ionisation (APCI) in the negative mode. The LC separations of the
      studied compounds and their MS parameters were optimised in order to improve
      selectivity and sensitivity. Separation was carried out with a C(18) column using
      methanol and 0.005% acid acetic as mobile phase in gradient mode. The molecular
      ion was selected for the quantitation in selective ion monitoring (SIM) mode. A
      solid-phase extraction (SPE) method was applied in order to preconcentrate the
      target analytes from water samples. However, extraction of the compounds from
      sediment and biota samples was carried out by liquid-solid extraction with
      methanol/water after studying the influence of other organic solvents. In
      addition, a clean-up step by SPE with HLB Oasis cartridges was necessary for
      sediments and biota. The proposed analytical methodology was validated in the
      target environmental matrices by the analysis of spiked blank matrix samples.
      Detection limits were 10-50 ng L(-1) for water, 1-5 microg kg(-1) for sediments
      and 2.5-5 microg kg(-1) for biota samples. Good recoveries and precision values
      were obtained for all matrices. This methodology has been successfully applied to
      the analysis of incurred water, sediment and biota samples from Andalusia
      (Spain).

PMID- 14963621
TI  - Voltage-gated Na+ channels: multiplicity of expression, plasticity, functional
      implications and pathophysiological aspects.
AB  - Voltage-gated Na+ channels (VGSCs) are well known for mediating regenerative cell
      membrane depolarization and conduction of electrical signalling in nerves and
      muscles. However, VGSCs may also be expressed in traditionally "non-excitable"
      cell types, including lymphocytes, glia, fibroblasts and metastatic cancer cells
      of epithelial origin. Both the diversity and modulation of VGSC expression are
      far more complex than was initially apparent. There are at least 10 different
      genes that encode the alpha-subunits of VGSCs. Since VGSCs can contribute to a
      range of human disease conditions, it is important to understand both the control
      and consequences of VGSC functioning and how these aspects may be altered under
      pathophysiological conditions. Such mechanisms can be at the transcriptional, pre
      translational or post-translational levels. This article reviews recent
      literature that has contributed to our understanding of how individual VGSC
      subtypes can generate their unique physiological signatures within different cell
      types. We also highlight emerging areas of interest, in particular, the finding
      of multiple expression of individual VGSC subtypes within single cells, the
      generation of alternative splice variants and the increasingly complex set of
      mechanisms of plasticity through which individual VGSC subtypes may be subtly
      controlled, including intracellular trafficking of VGSC protein.

PMID- 14963625
TI  - Detection of transgenes in soybean via a polymerase chain reaction and a simple
      bioluminometric assay based on a universal aequorin-labeled oligonucleotide
      probe.
AB  - The recombinant photoprotein aequorin was used as a reporter in highly sensitive
      and automatable hybridization assays for the analysis of transgenic sequences in
      genetically modified organisms (GMO). The terminator of the nopaline synthase
      gene (NOS) from Agrobacterium tumefaciens and the 35S promoter sequence were
      detected in genetically modified soybean. The endogenous, soybean-specific,
      lectin gene was also detected for confirmation of the integrity of extracted DNA.
      A universal detection reagent was produced through conjugation of aequorin to the
      oligonucleotide (dA)(30). Biotinylated (through PCR) products for the three
      target sequences were captured onto streptavidin-coated wells, and one strand was
      removed by NaOH treatment. The immobilized single-stranded DNAs were then
      hybridized with oligonucleotide probes consisting of a target-specific segment
      and a poly(dT) tail. This allowed the subsequent determination of all hybrids
      through the use of the (dA)(30)-aequorin conjugate as a universal reagent. The
      bound aequorin was measured by adding Ca(2+) and integrating the light emission
      for 3 s. As low as 2 pM (100 amol per well) of amplified DNA was detectable for
      all three targets, with a signal-to-background ratio of about 2. The analytical
      range extended up to 2000 pM. As low as 0.05% GMO content in soybean can be
      detected with a signal-to-background ratio of 8.2. The overall repeatability of
      the proposed assay, including DNA extraction, PCR, and hybridization assay,
      ranged from 7.5-19.8%. The use of a (dA)(30)-aequorin conjugate renders the assay
      configuration general for any target DNA, provided that the specific probe
      carries a poly(dT) tail.

PMID- 14963626
TI  - Surface acoustic waves for the characterization of BN-coated fibres observed by
      Brillouin light scattering.
AB  - The observation of acoustic phonons located at the surface of uncoated fibres or
      guided in thin films deposited on fibres by Brillouin light scattering
      spectroscopy (BLS) is reported. The BLS technique is non-destructive and non
      intrusive and is well applicable to non-planar sample geometries. Investigations
      were carried out on bundles of commercially available carbon fibres, in which a
      single fibre was 5 microm in diameter. With regard to the detected surface
      acoustic excitations, each fibre can be considered as an infinite halfspace owing
      to the large ratio of fibre diameter to wavelength. The shear modulus, which is
      highly relevant for the intended technical application, was determined by
      measurement of the Rayleigh mode phase velocity of the uncoated fibres. These
      fibre bundles were coated with boron nitride (BN) in a continuously driven
      thermal chemical vapour deposition (CVD) process using trimethyl borate and
      ammonia as precursors. In comparison to carbon, BN is expected to improve the
      mechanical properties of fibre-reinforced composites such as fracture toughness
      at high temperatures. The measured velocity dispersion of the Rayleigh mode of
      this film-on-substrate system permitted the comparison of the shear stiffness of
      the carbon fibre and of the BN film material. The results evidence the desired
      effect of a distinct stiffness reduction of the coated fibre relative to the
      uncoated fibre in the near-surface region. Additional information can be obtained
      on the homogeneity of the deposition across the whole fibre bundle.

PMID- 14963627
TI  - Urban ozone measurements using differential optical absorption spectroscopy.
AB  - In order to improve the air quality in Europe the European Commission has issued
      a number of directives with regard to acceptable levels of a range of gaseous
      pollutants, which includes ozone. Therefore, monitoring of this compound is
      necessary to comply with EU legislation, to provide improved pollution warnings
      for those who are sensitive to air pollutants as well as providing valuable data
      for environmental planning. Open-path spectroscopic techniques, such as
      differential optical absorption spectroscopy (DOAS), are ideal for monitoring
      pollutants because of the advantages they offer over classical methods and point
      source analysers. A DOAS system has been installed in Dublin city centre to
      monitor a range of criteria pollutants including ozone. Observations of urban
      background ozone concentrations are presented. The measurements are compared with
      those obtained using a UV point-source analyser and are presented in the context
      of the current EU directive. The influence of trans-boundary pollution from
      mainland Europe leading to ozone episodes is also discussed. Observations of high
      ozone during this measurement campaign coincided with the influx of
      photochemically polluted air masses which originated over continental Europe. For
      the analysed time interval, the data suggest that the ground ozone level in
      Dublin might be significantly influenced by long-range transport from the United
      Kingdom and continental Europe.

PMID- 14963630
TI  - Carbon sequestration and estimated carbon credit values as measured using 13C
      labelling and analysis by means of an optical breath test analyser.
AB  - Recent developments in optical systems (isotope-selective non-dispersive infrared
      spectrometry) for breath testing have provided a robust, low-cost option for
      undertaking (13)C analysis. Although these systems were initially developed for
      breath testing for Helicobacter pylori, they have an enormous potential as a soil
      science research tool. The relatively low cost of the equipment, US$15,000
      25,000, is within the research budgets of most institutes or universities. The
      simplicity of the mechanisms and optical nature mean that the equipment requires
      relatively low maintenance and minimal training. Thus methods were developed to
      prepare soil and plant materials for analysis using the breath test analyser.
      Results that compare conventional mass spectrometric methods with the breath test
      analyser will be presented. In combination with simple (13)C-plant-labeling
      techniques it is possible to devise methods for estimating carbon sequestration
      under different agronomic management practices within a short time frame. This
      enables assessment of the carbon credit value of a particular agronomic practice,
      which can in turn be used by policy makers for decision-making purposes. For
      global understanding of the effect of agricultural practices on the carbon cycle,
      data are required from a range of cropping systems and agro-ecological zones. The
      method and the approach described will enable collection of hard data within a
      reasonable time.

PMID- 14963632
TI  - Kinetic method for acetylsalicylic acid determination based on its inhibitory
      effect upon the catalytic decomposition of H(2)O(2).
AB  - The catalytic reaction of catalase was investigated, by means of a Clark oxygen
      sensor, in the presence of various concentrations of acetylsalicylic acid.
      Michaelis-Menten kinetic parameters were determined from Lineweaver-Burk plots,
      obtained in the absence and in the presence of the inhibitor. The inhibition
      pattern, suggested by the Lineweave-Burk plots, corresponds to a fully mixed
      inhibition mechanism. A kinetic method, based on the indicator reaction:
      [Formula: see text], was developed for the quantitative determination of
      acetylsalicylic acid. Calibration graphs of the reciprocal value of first-order
      rate constant versus acetylsalicylic concentration covered the concentration
      range (2.99-19.98)x10(-4) mol/L, while the detection limit was 4.12x10(-4) mol/L
      acetylsalicylic acid with a standard deviation of 2.1x10(-5) mol/L.

PMID- 14963633
TI  - Determination of trace amounts of phosphate by flow-injection photometry.
AB  - This paper describes a simple and rapid procedure for determination of traces of
      phosphate by means of molybdenum blue chemistry. The use of a cost-effective home
      made flow cell with a long path length in combination with a light emitting diode
      (LED) and a photodiode (PD) is demonstrated as a simple absorbance detector for
      flow-injection analysis. In this method, a sample is injected into the carrier
      stream through an injection valve and mixed online with mixed reagent (a mixture
      of molybdate, bismuth, and ascorbic acid in sulfuric acid). The color intensity
      of the resulting association complex, molybdenum blue, is measured
      photometrically ( lambda(max) 875 nm). The proposed method can be used to detect
      phosphate in the range 0.02-4.0 mg x L(-1) and the precision of the proposed
      procedure is less than 5% at 0.1 mg x L(-1) phosphorus as phosphate. The method
      has been successfully applied to a variety of natural water samples.

PMID- 14963634
TI  - Optimization of solid-phase extraction procedure for determination of
      polychlorinated dibenzo- p-dioxins, polychlorinated dibenzofurans, and coplanar
      polychlorinated biphenyls in humic acid containing water.
AB  - A solid-phase extraction (SPE) method was optimized for accurate determination of
      polychlorinated dibenzo- p-dioxins (PCDDs), polychlorinated dibenzofurans
      (PCDFs), and coplanar polychlorinated biphenyls (CoPCBs) in humic acid containing
      surface water. Recovery experiments using humic materials revealed that humic
      acids permit dioxins to pass through an octadecylsilica (C(18)) extraction disk
      by associating with them under weakly alkaline conditions. Acidification of the
      sample before percolation improved this otherwise insufficient recovery. The
      analysis of surface water acidified to pH 2 gave better recovery with surrogate
      standards and lower quantitative values for higher-chlorinated homologues than
      the sample at pH 9. In all samples, the native octachlorodibenzo- p-dioxin (OCDD)
      peak abundance showed no difference between at pH 2 and at pH 9, indicating
      overestimation of the quantitative value of the homologue at pH 9. Acidification
      of a humic acid containing water sample can avoid overestimation of higher
      chlorinated congeners caused by insufficient recovery of their corresponding
      surrogates.

PMID- 14963635
TI  - Separation of organoselenium compounds and their electrochemical detection.
AB  - A simplified procedure based on ion-exchange separation of selenourea (Se-U) and
      selenocystamine (Se-CM), which have very close half-wave potential when they are
      simultaneously analyzed by voltammetric techniques, has been developed and
      optimized. Thus, selenocystamine remains in the cation exchanger Purolite C 100
      H, whereas selenourea is found in the effluent and is determined by square wave
      cathodic stripping voltammetry using Na(2)CO(3 )as electrolyte. Selenocystamine
      is then eluted from the cation exchanger using 4 M HCl and analyzed by square
      wave cathodic stripping voltammetry in the HCl solution. For each voltammetric
      determination the corresponding parameters were investigated and optimized; the
      obtained detection limits were 0.3 ng Se mL(-1) for Se-CM and 2 ng Se mL(-1) for
      Se-U. A flow sheet for the separation of inorganic (Se(IV) and Se(VI)) and
      organoselenium compounds (Se-U, Se-CM, (CH(3))(2)Se(2), and (CH(3))(2)Se)
      developed for their electrochemical detection is presented and it was
      successfully applied to a certified reference material, an environmental soil
      sample, and a urine sample.

PMID- 14963637
TI  - Being an effective reviewer.

PMID- 14963638
TI  - Multidimensional LC-LC and LC-CE for high-resolution separations of biological
      molecules.
AB  - In multidimensional separations, two or more independent separation methods are
      coupled in an effort to resolve complex mixtures. The displacement mechanisms of
      each method should be orthogonal, such that little correlation exists between the
      retention of compounds in each dimension. When multiple orthogonal separation
      methods are coupled such that all sample components are subjected to complete
      analysis on all dimensions, the method is considered "comprehensive". The primary
      advantage of comprehensive multidimensional separations over their one
      dimensional counterparts is the potential for dramatically enhanced resolution.
      High resolving power can be achieved because the peak capacity of a comprehensive
      multidimensional separation is roughly equal to the product of the individual
      peak capacities of each dimension. In this review, the theory and instrumentation
      of two-dimensional liquid chromatography (LC-LC) and liquid chromatography
      capillary electrophoresis (LC-CE) separations are discussed. Some applications of
      these techniques to the separation of biological molecules are highlighted.
      Future directions for the development of multidimensional separations are also
      considered.

PMID- 14963639
TI  - Extracts from Rhois aromatica and Solidaginis virgaurea inhibit rat and human
      bladder contraction.
AB  - Since extracts from the plants Rhois aromatica and Solidaginis virgaurea are
      being used in the phytotherapy of bladder dysfunction including the overactive
      bladder syndrome, and since muscarinic receptors are the main pharmacological
      target in the treatment of bladder dysfunction, we have investigated whether
      these extracts can inhibit carbachol-induced, muscarinic receptor-mediated
      contraction of rat and human bladder. In vitro contraction experiments were
      performed with rat and human bladder strips. Radioligand binding and inositol
      phosphate accumulation studies were done with cells transfected with human M(2)
      or M(3) muscarinic receptors. Both extracts concentration-dependently (final
      concentrations 0.01-0.1%) inhibited carbachol-induced contraction of rat and
      human bladder with insurmountable antagonism. Radioligand binding experiments and
      inositol phosphate accumulation studies with cloned receptors demonstrated direct
      but non-competitive effects on muscarinic receptors. Reductions of KCl-induced
      bladder contraction demonstrated that inhibition by the higher extract
      concentrations also involved receptor-independent effects. We conclude that
      extracts from Rhois aromatica and Solidaginis virgaurea inhibit muscarinic
      receptor-mediated contraction of rat and human bladder. While this could
      contribute to the beneficial effects of these extracts in patients with bladder
      dysfunction, such therapeutic effects remain to be demonstrated in controlled
      clinical studies.

PMID- 14963640
TI  - Accelerated kindling development in mu-opioid receptor deficient mice.
AB  - The relevance of mu-opioid systems for central excitability and kindling related
      disturbed learning performance was underlined by investigations using mu-opioid
      receptor knockout mice. Mice lacking mu-opioid receptors showed an accelerated
      kindling development induced by the convulsant drug pentylenetetrazol. Blockade
      of delta-opioid receptors by naltrindole suppressing kindling development in wild
      type animals led to a further acceleration of kindled seizure development in the
      knockout mice. Mice lacking mu-opioid receptors showed such a low learning
      performance in the shuttle box, that the kindling induced learning deficit as
      seen in wild-type mice was not detected. The results were discussed on the basis
      of receptor binding studies with regard to subtypes of glutamatergic receptors,
      delta-opioid and somatostatin receptors. An increase in glutamate and
      somatostatin binding could contribute to the enhanced excitability in the-mu
      opioid receptor knockout mice.

PMID- 14963641
TI  - Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of
      cannabis, in acute carrageenan-induced inflammation in the rat paw.
AB  - Cannabidiol, the major non-psychoactive component of marijuana, has various
      pharmacological actions of clinical interest. It is reportedly effective as an
      anti-inflammatory and anti-arthritic in murine collagen-induced arthritis. The
      present study examined the anti-inflammatory and anti-hyperalgesic effects of
      cannabidiol, administered orally (5-40 mg/kg) once a day for 3 days after the
      onset of acute inflammation induced by intraplantar injection of 0.1 ml
      carrageenan (1% w/v in saline) in the rat. At the end of the treatment
      prostaglandin E2 (PGE2) was assayed in the plasma, and cyclooxygenase (COX)
      activity, production of nitric oxide (NO; nitrite/nitrate content), and of other
      oxygen-derived free radicals (malondialdehyde) in inflamed paw tissues. All these
      markers were significantly increased following carrageenan. Thermal hyperalgesia,
      induced by carrageenan and assessed by the plantar test, lasted 7 h. Cannabidiol
      had a time- and dose-dependent anti-hyperalgesic effect after a single injection.
      Edema following carrageenan peaked at 3 h and lasted 72 h; a single dose of
      cannabidiol reduced edema in a dose-dependent fashion and subsequent daily doses
      caused further time- and dose-related reductions. There were decreases in PGE2
      plasma levels, tissue COX activity, production of oxygen-derived free radicals,
      and NO after three doses of cannabidiol. The effect on NO seemed to depend on a
      lower expression of the endothelial isoform of NO synthase. In conclusion, oral
      cannabidiol has a beneficial action on two symptoms of established inflammation:
      edema and hyperalgesia.

PMID- 14963643
TI  - Dynamic elastic pressure-volume loops in healthy pigs recorded with inspiratory
      and expiratory sinusoidal flow modulation. Relationship to static pressure-volume
      loops.
AB  - OBJECTIVE: The objective was to analyse relationships between inspiratory and
      expiratory static and dynamic elastic pressure-volume (P(el)/V) curves in healthy
      pigs. DESIGN: The modulated low flow method was developed to allow studies also
      of the expiratory P(el)/V curves. Static P(el)/V (P(el,st)/V) and dynamic P(el)/V
      (P(el,dyn)/V) loops were studied in healthy pigs. SETTING: Animal research
      laboratory in a university hospital. MATERIAL: Ten healthy anaesthetised and
      paralysed pigs. INTERVENTIONS AND MEASUREMENTS: A computer controlled a Servo
      Ventilator 900C with respect to respiratory rate, inspiratory flow and expiratory
      pressure to achieve a sinusoidal modulation of inspiration and expiration for
      determination of P(el,dyn)/V loops from zero end-expiratory pressure (ZEEP) and
      from a positive end-expiratory pressure (PEEP) of 6 cmH(2)O to 20, 35 and 50
      cmH(2)O. The same system was used for studies of P(el,st)/V loops with the flow
      interruption method from ZEEP and PEEP to 35 cmH(2)O. Recordings were analysed
      with an iterative technique. RESULTS: The feasibility of automated determination
      of P(el,dyn)/V loops was demonstrated. Differences between P(el,dyn)/V and
      P(el,st)/V loops were explained by viscoelastic behaviour. P(el,st)/V loops
      recorded from PEEP to 35 cmH(2)O showed no significant hysteresis, indicating a
      non-significant surface tension hysteresis. P(el,dyn)/V loops from PEEP and both
      P(el,st)/V and P(el,dyn)/V loops from ZEEP to 35 cmH(2)O showed hysteresis. This
      indicates that lung collapse/re-expansion caused P(el)/V loop hysteresis which,
      in P(el,dyn)/V loops, was augmented by viscoelastic behaviour. CONCLUSIONS:
      Viscoelasticity influences P(el,dyn)/V curves. Hysteresis caused by surface
      tension merits re-evaluation. Lung collapse and re-expansion may be indicated by
      hysteresis of P(el)/V loops.

PMID- 14963644
TI  - Impaired chemoreflex sensitivity in adult patients with multiple organ
      dysfunction syndrome--the potential role of disease severity.
AB  - OBJECTIVE: The cardiac chemoreflex sensitivity is a powerful predictor of
      autonomic dysfunction in chronic heart failure and after myocardial infarction.
      The objective of the present study was to characterize cardiac chemoreflex
      sensitivity in patients with multiple organ dysfunction syndrome (MODS). We also
      aimed to elucidate the effect of the severity of MODS on the assessment of
      cardiac chemoreflex sensitivity. DESIGN: Prospective cohort study. SETTING:
      Twelve-bed medical intensive care unit in a university center. PATIENTS: Forty
      consecutively admitted patients with MODS during a 7-month period. Patients with
      MODS were identified by an APACHE II score of 20 or more. Sepsis was defined as a
      Sepsis Score, according to Elebute and Stoner, of 12 or more. INTERVENTIONS: The
      cardiac chemoreflex sensitivity was assessed using the regression of heart
      interval (ms) versus arterial oxygen pressure (mmHg). MEASUREMENTS AND RESULTS:
      First, we established a new method to assess cardiac chemoreflex sensitivity and
      applied it to healthy controls and patients. Second, we found that cardiac
      chemoreflex sensitivity correlated with the severity of MODS as calculated by the
      APACHE II score ( r(2)=0.34, p=0.001). This relation was best fitted by a model
      including minimum heart rate and standard bicarbonate in 24 h ( r(2)=0.5,
      p<0.001) and Glasgow Coma Scale ( r(2)=0.5, p=0.005). Age, however, did not
      significantly contribute ( r(2)=0.001, p=0.8). CONCLUSIONS: The calculation of
      cardiac chemoreflex sensitivity enabled us to quantify an important component of
      the cardiorespiratory interactions in patients with MODS. Severity of illness was
      a more pronounced determinant of impaired cardiac chemoreflex sensitivity than
      age. The quantification of the cardiorespiratory interactions by measuring the
      cardiac chemoreflex sensitivity has potential to identify a subgroup of patients
      with worse prognosis.

PMID- 14963645
TI  - Hyperbaric oxygen therapy prevents vascular derangement during zymosan-induced
      multiple-organ-failure syndrome.
AB  - OBJECTIVE: This study investigated the effects of hyperbaric oxygen (HBO) therapy
      on the cardiovascular alteration (e.g. mean arterial pressure, vascular
      reactivity of thoracic aorta rings changes) caused by zymosan in rats. DESIGN:
      Rats. SETTING: University research laboratory. INTERVENTION AND MEASUREMENTS: We
      investigated the effects of HBO therapy (2 ATA at the fourth and eleventh hours
      after study onset) on the cardiovascular alteration caused by zymosan (500 mg/kg,
      administered i.p. as a suspension in saline) in rats. Cardiovascular alterations
      were assessed 18 h after administration of zymosan and/or HBO therapy. RESULTS:
      Treatment of rats with HBO therapy attenuated the vasoplegic response to zymosan.
      In fact, the analysis of arterial pressure curves revealed no signs of vasoplegic
      shock. The aorta rings of animals treated with zymosan and HBO had a
      significantly increased contraction to norepinephrine (NE) and endothelin-1 (ET
      1) and dilation to acetylcholine (ACh) compared with the zymosan group. The HBO
      therapy also attenuated the increase of malondialdehyde (MDA) levels caused by
      zymosan in the aorta. Immunohistochemical analysis for nitrotyrosine and for iNOS
      revealed positive staining in the aorta from zymosan-treated rats. The degree of
      staining for nitrotyrosine and iNOS was markedly reduced in tissue sections
      obtained from zymosan-rats treated with HBO therapy. CONCLUSION: This study
      provides the first evidence that HBO therapy attenuates the degree of zymosan
      induced cardiovascular derangement in the rat.

PMID- 14963646
TI  - Adult-population incidence of severe sepsis in Australian and New Zealand
      intensive care units.
AB  - OBJECTIVE: To determine the population incidence and outcome of severe sepsis
      occurring in adult patients treated in Australian and New Zealand intensive care
      units (ICUs), and compare with recent retrospective estimates from the USA and
      UK. DESIGN: Inception cohort study. SETTING: Twenty-three closed multi
      disciplinary ICUs of 21 hospitals (16 tertiary and 5 university affiliated) in
      Australia and New Zealand. PATIENTS: A total of 5878 consecutive ICU admission
      episodes. MEASUREMENTS AND RESULTS: Main outcome measures were population-based
      incidence of severe sepsis, mortality at ICU discharge, mortality at 28 days
      after onset of severe sepsis, and mortality at hospital discharge. A total of 691
      patients, 11.8 (95% confidence intervals 10.9-12.6) per 100 ICU admissions, were
      diagnosed with 752 episodes of severe sepsis. Site of infection was pulmonary in
      50.3% of episodes and abdominal in 19.3% of episodes. The calculated incidence of
      severe sepsis in adults treated in Australian and New Zealand ICUs is 0.77 (0.76
      0.79) per 1000 of population. 26.5% of patients with severe sepsis died in ICU,
      32.4% died within 28 days of the diagnosis of severe sepsis and 37.5% died in
      hospital. CONCLUSION: In this prospective study, 11.8 patients per 100 ICU
      admissions were diagnosed with severe sepsis and the calculated annual incidence
      of severe sepsis in adult patients treated in Australian and New Zealand ICUs is
      0.77 per 1000 of population. This figure for the population incidence falls in
      the lower range of recent estimates from retrospective studies in the U.S. and
      the U.K.

PMID- 14963648
TI  - Silent myocardial infarction and its prognosis in a community-based cohort of
      Type 2 diabetic patients: the Fremantle Diabetes Study.
AB  - AIMS/HYPOTHESIS: Our study investigated the prognosis of Type 2 diabetic patients
      with silent myocardial infarction in a community-based cohort. METHODS: We
      analysed data from 1269 patients with Type 2 diabetes mellitus from a community
      based observational study of diabetes care, control and complications. Silent
      myocardial infarction was defined as Q waves (Minnesota codes 1.1, 1.2) on a
      baseline electrocardiogram in the absence of a history or symptoms of CHD.
      RESULTS: Silent myocardial infarction was present in 3.9% of patients, or 44% of
      all Q-wave myocardial infarctions. The patients were subdivided into those with
      (i). no clinical or Q-wave evidence of myocardial infarction (Group 1), (ii).
      silent myocardial infarction (Group 2), (iii). self-reported CHD but no Q waves
      (Group 3), and (iv) self-reported CHD and Q waves (Group 4). Compared to Groups 3
      and 4, Group 2 patients were more likely to be women, less likely to have smoked,
      and had higher serum HDL-cholesterol concentrations and higher blood pressure.
      Over an average of seven years, and after adjusting for other independent
      predictors of death, all-cause and CHD mortality were similar in Groups 1 and 2
      and greater (twofold for all-cause and fourfold for CHD mortality) in Groups 3
      and 4. CONCLUSIONS/INTERPRETATION: Silent myocardial infarction is common in Type
      2 diabetes and has a prognosis similar to that in patients without a history of
      CHD or Q waves.

PMID- 14963649
TI  - Altered gene expression with abnormal patterning of the telencephalon in embryos
      of diabetic Albino Swiss mice.
AB  - AIMS/HYPOTHESIS: Several studies have shown that maternal diabetes increases the
      risk of congenital malformations in various organ systems including the neural
      tube. The present study analysed molecular and morphological changes in the
      forebrain of embryos from diabetic Albino Swiss mice. METHODS: Maternal diabetes
      induced morphological changes in the forebrain were examined histologically. Cell
      proliferation index was assayed by BrdU labelling. In situ hybridisation and
      quantitative real-time PCR were used to analyse the expression of genes coding
      for sonic hedgehog ( Shh), Nkx2.1, brain factor-1 ( BF-1) and bone morphogenetic
      protein-4 ( Bmp4) that control forebrain patterning. RESULTS: There were no
      distinguishable abnormalities in the forebrain of embryos from diabetic
      pregnancies on embryonic day 0.5. At embryonic day 11.5, embryos of diabetic
      pregnancies displayed a fusion and thickening of the ventral telencephalic
      neuroepithelium and a partial absence of the dorsal telencephalon, indicating a
      severe patterning defect in the dorsoventral axis of the telencephalon. The cell
      proliferation index was also higher in the ventral telencephalon of these
      embryos. Molecular analyses indicated that expression of Shh, Nkx2.1 and BF-1 was
      increased and their expression domains expanded dorsally in the ventral
      telencephalon in embryos of diabetic mice at embryonic day 11.5. The expression
      of Bmp4 was reduced in the dorsal forebrain of these embryos. At embryonic day
      8.5, only Shh expression was increased. CONCLUSIONS/INTERPRETATION: Altered
      expression of various genes involved in dorsoventral patterning of the forebrain
      is associated with forebrain malformations in embryos of diabetic mice.

PMID- 14963650
TI  - Enhanced P-selectin expression and increased soluble CD40 Ligand in patients with
      Type 1 diabetes mellitus and microangiopathy: evidence for platelet hyperactivity
      and chronic inflammation.
AB  - AIMS/HYPOTHESIS: Platelet activation, endothelial dysfunction and inflammation
      may be involved in early stages of diabetic microangiopathy. We therefore
      investigated patients with Type 1 diabetes mellitus, without ( n=19) and with (
      n=20) microangiopathy, matched for glycaemic control and duration of disease, and
      matched with healthy control subjects ( n=27). METHODS: Platelet activation was
      measured as platelet P-selectin expression using whole blood flow cytometry and
      as soluble P-selectin by immunoassay. Von Willebrand factor antigen in plasma,
      serum soluble E-selectin, CD40 ligand (sCD40L) and C-reactive protein (CRP)
      served as markers for endothelial function and inflammation. RESULTS: Thrombin
      induced platelet P-selectin expression was enhanced, and soluble P-selectin and
      sCD40L concentrations were increased in patients with microangiopathy compared
      with the control subjects ( p<0.01 for both) and with patients without
      microangiopathy ( p<0.05 for P-selectin expression and sP-selectin), whereas all
      three parameters were similar in patients without microangiopathy and in the
      control subjects. CRP and soluble E-selectin were increased in patients with
      microangiopathy, compared with the control subjects ( p<0.01 and p<0.05), whereas
      von Willebrand factor did not differ between the groups.
      CONCLUSIONS/INTERPRETATION: Microangiopathy in Type 1 diabetes is associated with
      platelet hyperactivity, endothelial dysfunction and low-grade inflammation,
      indicating an increased risk for cardiovascular disease.

PMID- 14963651
TI  - A genetic analysis of adult plant resistance to stripe rust in the wheat cultivar
      Kariega.
AB  - The wheat cultivar Kariega expresses complete adult plant resistance to stripe
      rust in South Africa. The aim of this investigation was to determine the extent
      and nature of variability in stripe rust resistance in a population of 150
      doubled haploid lines generated from a cross between Kariega and the susceptible
      cultivar Avocet S. Analysis of field data for adult plant stripe rust resistance
      identified two major QTLs and two minor QTLs in the resistant cultivar Kariega.
      The two major QTLs were located on chromosomes 7D ( QYr.sgi-7D) and 2B ( QYr.sgi
      2B.1), contributing 29% and 30% to the phenotypic variance, respectively. QYr.sgi
      2B.1 is primarily associated with a chlorotic and/or necrotic response, unlike
      QYr.sgi-7D, which is believed to be the adult plant resistance gene Yr18. These
      two QTLs for adult plant resistance in Kariega appear to represent different
      forms of resistance, where QYr.sgi-7D may represent potentially more durable
      resistance than QYr.sgi-2B.1. Mixture model analysis of the field leaf infection
      scores suggested a genetic model involving two independent genes combining in a
      classical, epistatic manner. The results of the QTL analysis demonstrate its
      higher resolution power compared to the mixture model analysis by detecting the
      presence of minor QTLs.

PMID- 14963652
TI  - Phylogenetic and evolutionary relationships between Elymus humidus and other
      Elymus species based on sequencing of non-coding regions of cpDNA and AFLP of
      nuclear DNA.
AB  - Species of the genus Elymus are closely related to some important cereal crops
      and may thus serve as potential alien genetic resources for the improvement of
      these crops. E. humidus is indigenous to Japan and is well adapted to a humid
      climate. However, the phylogenetic and evolutionary relationships between E.
      humidus and other Elymus species are unclear. To elucidate these relationships,
      we examined the sequences of three non-coding regions of chloroplast DNA (cpDNA)
      and the amplified fragment length polymorphism (AFLP) variation of nuclear DNA in
      E. humidus and other related species. A total of 15 sequence mutations from the
      three non-coding regions, trnL-trnF, trnF- ndhJ(C), and atpB-rbcL, covering
      approximately 1,800 bp, were detected in the Elymus species. A phylogenic tree
      resulting from the cpDNA sequence data revealed that all the species containing
      the St nuclear genome (St, StH, StY, and StHY) formed a well-supported clade that
      is remote from the Hordeum species (H). This result strongly supports the finding
      that Pseudoroegneria is the maternal genome donor to the genus Elymus. In
      addition, E. humidus showed the closest relationship with the cpDNA genome of the
      Pseudoroegneria species. The AFLP analysis detected 281 polymorphic bands with 11
      AFLP primer combinations. The AFLP result showed that E. humidus is relatively
      closer to E. tsukushiensis. However, the cpDNA sequencing results indicated that
      E. humidus and E. tsukushiensis have different cytoplasmic origins. Our results
      suggest that the evolutionary process between E. humidus and E. tsukushiensis is
      not monophyletic, although the two species have similar morphological characters
      and adaptability.

PMID- 14963653
TI  - Metabolic control analysis as a mechanism that conserves genetic variance during
      advanced cycle breeding.
AB  - The recycling of elite inbreds (i.e., advanced cycle breeding) has led to
      significant genetic gains but also to a narrow gene pool in plant breeding
      programs. Sustained yield improvements in many crops have suggested that genetic
      variance is not depleted at a rate predicted by an additive genetic model. Unlike
      the additive model in classical quantitative genetic theory, metabolic control
      analysis relates the variation in a biochemical process with the genetic
      variation in a quantitative trait. Our objective was to determine whether
      metabolic control analysis is a mechanism that slows the decrease in genetic
      variance during advanced cycle breeding. Three cycles of advanced cycle breeding
      were simulated with 10, 50, or 100 quantitative trait loci (QTL) controlling a
      trait. In metabolic control analysis, these QTL coded for enzymes involved in a
      linear metabolic pathway that converted a substrate into a product. In the
      absence of selection, both the additive model and the metabolic control analysis
      model led to about a 50% reduction in genetic variance from cycle to cycle. With
      selection, the additive model led to a 50-58% reduction in genetic variance, but
      the metabolic control analysis model generally led to only a 12-54% reduction. We
      suggest selection in a metabolic control analysis model as a mechanism that slows
      the decrease in genetic variance during advanced cycle breeding. This
      conservation of genetic variance would allow breeders to achieve genetic gains
      for a longer period than expected under the additive model.

PMID- 14963654
TI  - The nematode-resistance gene, Mi-1, is associated with an inverted chromosomal
      segment in susceptible compared to resistant tomato.
AB  - The gene Mi-1 confers effective resistance in tomato ( Lycopersicon esculentum)
      against root-knot nematodes and some isolates of potato aphid. This locus was
      introgressed from L. peruvianum into the corresponding region on chromosome 6 in
      tomato. In nematode-resistant tomato, Mi-1 and six homologs are grouped into two
      clusters separated by 300 kb. Analysis of BAC clones revealed that the Mi-1 locus
      from susceptible tomato carried the same number and distribution of Mi-1
      homologs, as did the resistant locus. Molecular markers flanking the resistant
      and susceptible loci were in the same relative orientation, but markers between
      the two clusters were in an inverse orientation. The simplest explanation for
      these observations is that there is an inversion between the two clusters of
      homologs when comparing the Mi-1 loci from L. esculentum and L. peruvianum. Such
      an inversion may explain previous observations of severe recombination
      suppression in the region. Two Mi-1 homologs identified from the BAC library
      derived from susceptible tomato are not linked to the chromosome 6 locus, but map
      to chromosome 5 in regions known to contain resistance gene loci in other
      solanaceous species.

PMID- 14963655
TI  - [Noninvasive diagnosis of coronary artery disease].
AB  - BACKGROUND: Coronary artery disease (CAD) is one of the most common diseases that
      accounts for a considerable part of health care reimbursement. Thus, noninvasive
      diagnosis of CAD is likewise of pivotal importance for medical care today.
      NONINVASIVE DIAGNOSIS OF CAD: In this review, the authors present the entire
      spectrum of noninvasive diagnostic methods available for CAD starting with a
      Ergomedescription and discussion of the simplest and most important clinical
      approaches (patients' complaints, risk factors, electrocardiogram, and treadmill
      test). The established imaging modalities for diagnosing CAD (echocardiography,
      stress echocardiography, and scintigraphy including the SPECT and PET technique)
      are presented outlining their specific advantages and disadvantages. Finally, the
      authors discuss the most recent imaging modalities for the diagnosis of CAD
      (multislice computed tomography [MSCT] and magnetic resonance imaging [MRI]).
      MSCT allows for performing high-quality noninvasive coronary angiography, whereas
      MRI enables exact visualization of myocardial function, perfusion, and viability.
      CONCLUSION: The comprehensive assessment possible with MSCT and MRI and future
      developments will change the significance and importance of the conventional
      diagnostic methods for the diagnosis of CAD in the near future.

PMID- 14963656
TI  - [Interactions of statins with antithrombotic drugs].
AB  - Due to a wealth of scientific clinical data, statins are being extensively used
      for the primary and secondary prevention of ischemic events. Therefore, statins
      play a major part in the pharmacological treatment of cardiovascular disease.
      Even before it became apparent that statins are effective despite normal baseline
      lipid levels, it was known that statins exert additional effects on the vascular
      wall that are independent of lipid lowering and protective toward the
      arteriosclerotic plaque. Some of these pleiotropic effects are related to
      hemostasis: through profibrinolytic, antiadhesive and antiaggregatory mechanisms,
      statins act antithrombotic. Based on experimental results, concerns were brought
      forward Simthat atorvastatin interferes with the antithrombotic effects of the
      ADP-receptor inhibitor prodrug, clopidogrel, due to competitive affinity to liver
      enzymes. So far, however, other experimental as well as clinical data do not
      support the hypothesis that atorvastatin or any other statin affects the
      antithrombotic potency of clopidogrel. The aforementioned issues will be
      discussed.

PMID- 14963657
TI  - [Treatment of Graves' ophthalmopathy with oral or intravenous corticosteroids].
AB  - BACKGROUND: Oral or intravenous corticosteroids are the first choice of
      clinicians in medical treatment of Graves' ophthalmopathy. Most clinicians use
      high-dose intravenous corticosteroid pulse therapy only in cases of severe
      ophthalmopathy. However, there are reports about smaller side effects of
      intravenous steroids in comparison to oral therapy. Therefore, clinicians have
      the problem to choose the optimal therapy (oral vs. intravenous), duration of
      treatment and doses of corticosteroids. METHODS: Randomized, controlled studies
      comparing oral versus intravenous corticosteroids in the therapy of Graves'
      ophthalmopathy were selected. RESULTS: Both forms of application are able to
      reduce the clinical symptoms of Graves' ophthalmopathy. Therefore, oral and
      intravenous corticosteroid therapies are evidence-based. Most studies used
      uniform drug regimen protocols for oral application of corticosteroids with
      initial dosages of 60-100 mg (7-14 days) and dose reduction over several months.
      Drug regimen protocols for intravenous application were more different with
      initial dosages of 500-1,000 mg methylprednisolone at distinct intervals.
      Corticosteroid doses in the studies varied between 1-21 g. The beneficial
      therapeutic effect on clinical activity of Graves' ophthalmopathy was pronounced
      in the intravenous corticosteroid application form in two studies. CONCLUSION:
      Oral and intravenous forms of corticosteroid therapy are appropriate to reduce
      clinical symptoms of Graves' ophthalmopathy. However, most of the published
      studies are not eligible to compare effectiveness and side effects of both
      therapy regimens and to identify the most appropriate method.

PMID- 14963658
TI  - [Dementia or delirium? A frequent differential diagnosis in elderly patients].

PMID- 14963659
TI  - [Contrast-enhanced sonography using Levovist is decisive for staging and
      therapeutic schedule in hepatocellular carcinoma].
AB  - In a 65-year-old female patient, B-mode sonography detected a single focal lesion
      in the right liver lobe with a diameter < 3 cm. Histopathologic examination
      revealed a low differentiated hepatocellular carcinoma (HCC; G3). Tumor staging
      was performed by CT (computed tomography) scan and Resovist MRI (magnetic
      resonance imaging). Both examinations found a single liver lesion without signs
      of additional focal hepatic lesions. In addition, phase-inversion sonography in
      the late phase was performed using the ultrasound contrast agent Levovist. This
      examination of late-phase Levovist uptake detected more than five additional
      focal hepatic lesions in the right liver lobe, which were invisible by CT scan
      and Resovist MRI. This finding of multiloculated HCC was very important to decide
      on the patient's correct therapy. While liver transplantation is the treatment of
      choice in single HCC < 3 cm, it is contraindicated in multicentric HCC. In the
      patient described here, hemihepatectomy of the right liver lobe was performed.
      The histopathologic examination of the resected liver confirmed the diagnosis of
      multicentric HCC, which was noninvasively diagnosed only by contrast-enhanced
      sonography, but not by CT scan or MRI.

PMID- 14963660
TI  - [Stroke as secondary diagnosis].

PMID- 14963661
TI  - [Small intestine diverticulosis -- a rare cause of gastrointestinal bleeding].

PMID- 14963662
TI  - [Clinical medicine, clinical research, and clinical epidemiology].

PMID- 14963663
TI  - [Telecare of patients with chronic obstructive airway diseases].
AB  - In view of the limited resources of health systems, telemedicine offers
      possibilities to supplement the known forms of care and supervision of patients
      and to intensify them on the side of patients as well as of medical care.
      Telemonitoring adds to but does not replace traditional home visits or the
      medical consultations. It is clearly structured, reproducible, and based on
      modern technology for communication between patients and doctors. In this way
      "flying visits" can be made to the patient with a high frequency which otherwise
      would never be possible for financial and practical reasons. They also serve for
      defining the right time for seeing the patient personally. In any case, regular
      transmissions of lung function values insure a close contact of COPD or asthma
      patients to specialized institutions without impairing or ignoring medical home
      care. Whether it will be possible to react more quickly to disease changes by
      telemetric means or whether other treatment advantages will result remains yet to
      be seen. Results, so far, are encouraging in such a way that the use of
      telemedical means in chronically ill patients will be further evaluated, also in
      other than pulmonary diseases.

PMID- 14963664
TI  - The natriuretic peptides.
AB  - The natriuretic peptides are a family of widely distributed, but evolutionarily
      conserved, polypeptide mediators that exert a range of actions throughout the
      body. In cardiovascular homeostasis, the endocrine roles of the cardiac-derived
      atrial and B-type natriuretic peptide (ANP and BNP) in regulating central fluid
      volume and blood pressure have been recognised for two decades. However, there is
      a growing realisation that natriuretic peptide actions go far beyond their volume
      regulating effects. These pleiotropic actions include local (autocrine/paracrine)
      regulatory actions of ANP and BNP within the heart, and of another natriuretic
      peptide, CNP, within the vessel wall. Effects on function and growth of the local
      tissue environment are likely to be of great importance, especially in disease
      states where tissue and circulating levels of ANP and BNP rise markedly. At
      present, the relevance of other natriuretic peptides (notably uroguanylin and
      DNP) to human physiology and pathology remain uncertain. Other articles in this
      issue of Basic Research in Cardiology review the molecular physiology of
      natriuretic peptide signalling, with a particular emphasis on the lessons from
      genetically targetted mice; the vascular activity of natriuretic peptides; the
      regulation and roles of natriuretic peptides in ischaemic myocardium; and the
      diagnostic, prognostic and therapeutic roles of natriuretic peptides in heart
      failure.

PMID- 14963665
TI  - Molecular physiology of natriuretic peptide signalling.
AB  - The natriuretic peptide family consists of three homologous members, atrial
      (ANP), B-type (BNP) and C-type natriuretic peptides (CNP). These small peptides
      activate specific membrane-bound guanylyl cyclase (GC) receptors (GC-A and GC-B),
      thus modulating cellular functions via the intracellular second messenger, cyclic
      GMP. Since the original discovery of cardiac ANP more than two decades ago, the
      application of gene targeting technology in mice has provided new valuable
      information regarding the molecular physiology and diverse biological functions
      of natriuretic peptides and their receptors. The GC-A and ANP gene knock-outs
      demonstrated that this signalling system is not only essential in the maintenance
      of normal blood pressure and volume, but also has local, growth-moderating
      functions within the heart itself. Disruption of the genes encoding BNP, CNP or
      the CNP-receptor, GC-B, demonstrated that these "natriuretic peptides" are in
      fact unlikely to physiologically regulate renal sodium excretion but instead may
      exert important autocrine/paracrine cGMP-mediated effects on cellular
      proliferation and differentiation in different tissues. Notably, the intestinal
      peptide uroguanylin, which activates a third guanylyl cyclase (GC-C), exerts
      diuretic/natriuretic activity and links the intestine and kidney in an endocrine
      way to modulate renal function in response to oral salt load. Reviewed here is
      the physiology and biochemistry of natriuretic peptides and their guanylyl
      cyclase receptors, with special focus on the information gained to date from
      targeted disruption of specific members of this peptide family, their receptors,
      or effector molecules in the murine system.

PMID- 14963666
TI  - Vascular actions of natriuretic peptides. Cyclic GMP-dependent and -independent
      mechanisms.
AB  - Natriuretic peptides play important roles in the regulation of cardiovascular
      homeostasis. The endocrine actions of atrial natriuretic peptide (ANP) and brain
      natriuretic peptide (BNP) complement the paracrine effects of C-type natriuretic
      peptide (CNP) and urodilatin to regulate vascular smooth muscle tone, fluid and
      electrolyte balance and cardiac morphology. As a consequence, aberrant
      natriuretic peptide production and/or activity have been linked to a number of
      cardiovascular disorders and interventions that selectively modulate these
      vasoactive peptides may be of therapeutic benefit. This review will outline the
      structure, expression and vascular actions of natriuretic peptides and their
      endogenous receptors and highlight recent work that has revealed important
      interactions between the cyclic GMP producing particulate and soluble guanylate
      cyclases, thereby linking the cardiovascular actions of natriuretic peptides and
      nitric oxide, and a role for CNP as an endothelium-derived hyperpolarising factor
      (EDHF).

PMID- 14963667
TI  - Natriuretic peptides and myocardial ischaemia.
AB  - In both experimental and clinical myocardial ischaemia, release of BNP occurs
      rapidly from ventricular myocardium, prompting speculation that the early
      activation of the natriuretic peptide receptor/cGMP signalling system may be an
      important autocrine/paracrine response to ischaemia. Among the growing list of
      pleiotropic actions of natriuretic peptides is the attenuation of tissue
      susceptibility to ischaemic injury. BNP and other natriuretic peptides limit the
      extent of tissue infarction during ischaemia and reperfusion. The mechanism of
      cytoprotection is related to cGMP accumulation and opening of ATP-sensitive K(+)
      channels. The effects of longer-term upregulation of natriuretic peptide
      expression in the heart following myocardial infarction could include the
      suppression of growth and proliferative responses in myocytes and fibroblasts.
      Thus, chronic elevation of natriuretic peptide expression in infarcted myocardium
      probably represents a negative regulatory system to counter the pro-hypertrophic
      and pro-fibrotic signalling activated by other mediators such as angiotensin II
      and catecholamines. The acute and chronic actions of natriuretic peptides in
      myocardial ischaemia suggest a profile of activity that may be therapeutically
      beneficial in the management of patients with acute coronary syndromes and for
      the optimisation of post-infarction remodelling.

PMID- 14963668
TI  - The natriuretic peptides in heart failure.
AB  - Synthesis and release of the natriuretic peptides rises incrementally with
      increasing degrees of cardiac dysfunction. The prime stimulus is intracardiac
      distending pressures with modulating influences including age, gender, renal
      function and other aspects of neurohormonal status. Measurements of plasma
      natriuretic peptide concentrations and of B-type natriuretic peptide and amino
      terminal pro-B-type natriuretic peptide, in particular, show promise in diagnosis
      of heart failure, risk stratification in those with known heart disease, and in
      adjustment of therapy. Recombinant B-type natriuretic peptide itself can be
      administered as a treatment. These diagnostic, prognostic and therapeutic
      applications of B-type natriuretic peptide require a considerable expansion
      beyond current evidence, but it appears likely that the true role of plasma
      peptide measurements and peptide administration will become firmly established
      within the coming 5 year period.

PMID- 14963669
TI  - Thyroid hormone and phenotypes of cardioprotection.
AB  - Thyroid hormone has multiple effects on the cardiovascular system with important
      physiological consequences. Several genes that encode important regulatory and
      structural proteins in the heart have been shown to be thyroid hormone
      responsive. More notably, certain effects of thyroid hormone have been exploited
      therapeutically. Thyroid hormone is currently being evaluated as an inotrope and
      vasodilator in various clinical settings. Furthermore, new information has been
      recently accumulated on the role of thyroid hormone in the response of the heart
      to ischaemic stress. In fact, hyperthyroid and hypothyroid hearts display a
      phenotype of cardioprotection against ischaemia-reperfusion. Based on this
      evidence, the various actions of thyroid hormone on the cardiovascular system are
      highlighted in this review. Thyroid hormone, although limited by its adverse
      effects, might prove a suitable treatment for cardiovascular illnesses. Various
      thyroid hormone analogues are currently under development.

PMID- 14963670
TI  - Therapeutic angiogenesis. Devising new strategies based on past experiences.
AB  - Therapeutic angiogenesis improves tissue ischemia by supplementing and supporting
      the intrinsic process of angiogenesis. Besides direct administration of
      angiogenic growth factor proteins, injection of naked DNA, non-viral vectors and
      viral vector constructs carrying angiogenic genes have been used. A novel
      approach is to achieve therapeutic angiogenesis through cell mediated gene
      transfer. Genetically modulated cells carrying exogenous genes encoding for
      angiogenic factors and the cells with inherent ability to secrete angiogenic
      cytokines, such as bone marrow stem cells, embryonic stem cells and endothelial
      progenitor cells, have been used to achieve revascularization. This review
      discusses proof of the concept pre-clinical studies and phase-I/II human trials
      using VEGF, and cellular angiogenesis at length in the light of the literature
      and analyzes the problems and considerations of these approaches as a treatment
      strategy in the clinical perspective for the treatment of ischemic heart disease.

PMID- 14963671
TI  - Cardiac dysfunction in the Goto-Kakizaki rat. A model of type II diabetes
      mellitus.
AB  - METHODS: Both isolated perfused hearts and isolated ventricular myocytes from GK
      and matched control Wistar rat hearts were studied. Percent myocyte twitch
      shortening (%TS) and corresponding intracellular calcium transients (indo-1
      fluorescence ratio, R) were measured over a range of stimulation frequencies (0.5
      2.5 Hz; 32 degrees C, n = 16-24 cells). In isolated Langendorff-perfused hearts,
      we measured systolic LV pressure (LVP(max)), left ventricular end diastolic
      pressure (LVEDP), maximal rate of LV pressure rise (LV dP/dt(max)) and fall (LV
      dP/dt(min)) and isovolumic LV relaxation (exponential time constant, T) both at
      baseline and during brief (10 minutes) hypoxia. RESULTS: The %TS and
      corresponding indo-1 R were similar between GK and control myocytes at all
      stimulation frequencies (e.g. at 2.5 Hz: % TS = 8.6 +/- 0.77 and 8.2 +/- 0.19; R
      = 0.19 +/- 0.009 and 0.18 +/- 0.018, GK and control respectively, P = NS).
      Similarly, there were no significant differences in baseline LVP(max) (129 +/-
      6.2 and 135 +/- 9.6 mmHg; GK and control respectively, P = NS), LV dP/dt(max)
      (3169.5 +/- 165.80 and 3390.6 +/- 232.60 mmHg/s; GK and control respectively, P =
      NS), LV dP/dt(min) or T (24 +/- 0.7 and 25 +/- 0.6 ms, GK and control
      respectively, P = NS). During 10 min hypoxia, LV dP/dt(max) decreased
      significantly more, and LVEDP and T increased significantly more, in GK compared
      to control hearts (LV dP/dt(max): 668.90 +/- 32.8 versus 1027.10 +/- 84.0 mmHg/s;
      LVEDP: 21.4 +/- 4.3 versus 11.6 +/- 0.6 mmHg; T: 102 +/- 13.8 versus 56 +/- 3.0
      ms; GK versus control respectively; all P < 0.05). These abnormalities in GK
      hearts were reversed with acute addition of insulin (0.01 i. u./ml) to the
      perfusion buffer. CONCLUSION: The GK model of Type II diabetes displays a mild
      cardiomyopathy evident as exaggerated diastolic dysfunction during hypoxia. The
      mechanism is likely to involve substrate deficiency. Experimental study of
      cardiac function in the diabetic heart has focussed mostly on models of Type I
      diabetes. We studied cardiac function in the Goto-Kakizaki (GK) rat, an inbred
      model of spontaneous non-obese, Type II diabetes.

PMID- 14963672
TI  - Ventricular arrhythmias triggered by alerting stimuli in conscious rabbits pre
      treated with dofetilide.
AB  - We tested whether normally benign alerting/arousing stimuli provoke cardiac
      arrhythmias in conscious rabbits with electrically unstable myocardium. Alerting
      stimuli (loud sound, tapping and moving the cage, pinprick, inhalation of
      formaldehyde vapour) were presented before and after administration of dofetilide
      to conscious unrestrained rabbits (New Zealand White). Dofetilide (0.28-3.0 mg/kg
      i. v.) caused prolongation of QT interval (from 131 +/- 9 to 217 +/- 11 ms; p <
      0.01, n = 6) and Tpeak-Tend interval (from 34 +/- 5 to 81 +/- 9 ms; p < 0.01, n =
      6), altered ventricular conductance, and caused appearance of spontaneous
      ventricular ectopic beats. Alerting stimuli elicited ventricular ectopic beats in
      18/30 trials in all dofetilide-treated animals, with a short latency (3.1 +/- 0.4
      s). Formaldehyde vapour, in addition, elicited profound bradycardia, and
      precipitated non-sustained polymorphic ventricular tachycardia (torsades de
      points) lasting 0.6-8.5 s in 5/6 animals. These arrhythmias occurred also with a
      short latency (mean 8.7 +/- 1.6 s). Betaadrenergic blockade with propranolol (1.5
      mg/kg i. v.) abolished spontaneous ventricular ectopy, suppressed torsades de
      points precipitated by formaldehyde, and significantly (p < 0.05) reduced the
      number of ventricular ectopic beats triggered by alerting stimuli. In predisposed
      hearts, alerting stimuli precipitate arrhythmias by producing transient increases
      in sympathetic discharge in the ventricular myocardium. Vagally induced
      bradycardia with concurrent ventricular beta-adrenoreceptor activation may
      underlie development of torsades de points in patients with long QT syndrome
      precipitated by swimming, diving or facial immersion.

PMID- 14963673
TI  - Muscle sympathetic baroreflex sensitivity is different at rest and during evoked
      hypotension.
AB  - Arterial muscle sympathetic baroreflexes are frequently assessed using
      pharmacologically evoked decrements in arterial blood pressure. Since drugs
      administered for baroreflex tests may themselves alter the sympathetic response
      to evoked pressure variations we proposed a method to determine sympathetic
      baroreflex gain during spontaneous fluctuations in arterial pressure at rest and
      tested the null hypothesis that baroreflex gain assessed during spontaneous
      fluctuations in arterial pressure equals baroreflex gain determined during evoked
      hypotension. Muscle sympathetic nerve activity (MSA), arterial blood pressure,
      and heart rate were assessed at rest in 15 healthy volunteers (age: 29 years +/-
      5, mean +/- SD). All diastolic pressures sampled during a 5 min period were
      grouped in intervals of 1 mmHg and the burst incidence per interval was
      calculated. The slope of the regression line of burst incidence and diastolic
      pressure represents baroreflex gain during spontaneous fluctuations in arterial
      pressure. In the same volunteers, burst incidence was also determined over 30 s
      periods before and after a decrease in arterial pressure evoked by nitroprusside
      (SNP, 2-3 micro g kg(-1) i. v.). The relationship between mean MSA burst
      incidence and diastolic arterial pressure was compared before and after the
      pressure decrease yielding an average baroreflex "gain" during evoked
      hypotension. Average baroreflex "gain" assessed by this conventional method was
      compared to baroreflex gain assessed during spontaneous arterial pressure
      fluctuations by Bland-Altman analysis and correlation analysis. Resting MSA was
      28 bursts/100 heart beats +/- 10 at a diastolic pressure of 71 mmHg +/- 11.
      Baroreflex gain during spontaneous arterial pressure fluctuations was 4.0% mmHg(
      1) +/- 1.9 and was significantly greater than the average "gain" assessed during
      evoked hypotension (2.1% mmHg(-1) +/- 1.6). Individual values for baroreflex gain
      determined with both methods did not correlate (r = 0.1, p = 0.8). Baroreflex
      gain as determined during spontaneous arterial pressure fluctuations differs from
      that assessed during SNP-evoked hypotension, possibly due to intrinsic effects of
      SNP on the baroreflex. Thus, caution should be exercised when interpreting
      baroreflex gain derived during SNP-evoked hypotension.

PMID- 14963674
TI  - Targeting the inflammatory component in atherosclerotic lesions vulnerable to
      rupture.
AB  - Thrombosis of the coronary artery following plaque rupture is the commonest
      substrate of acute coronary events. The detection of atherosclerotic plaques
      prone to rupture would allow identifying patients at risk for acute coronary
      events and aggressive intervention. It has been assumed that the plaque
      morphology happens to be the major determinant for clinical outcome. The risk of
      plaque rupture depends upon the prevalence of plaques that have a large lipid
      core, a thin fibrous cap, and a dense inflammation of the fibrous cap. Evaluating
      monocytes and the lipid core and their proportions in the atherosclerotic lesion
      by novel radionuclide imaging strategies may predict a likelihood of an acute
      coronary event.

PMID- 14963675
TI  - Beneficial effects of statins in patients with non-ischemic heart failure.
AB  - OBJECTIVE: HMG CoA reductase inhibitors (statins) may exert a wide array of
      cholesterol independent effects including antihypertrophic effects on the heart.
      Their role in the treatment of heart failure has not been studied. METHODS AND
      RESULTS: 15 patients with heart failure NYHA II-III based on non-ischemic dilated
      cardiomyopathy were randomized in a double-blind study to 0.4 mg cerivastatin or
      placebo for an average treatment period of 20 weeks. Quality of life and exercise
      capacity increased significantly in the statin treatment but not in the placebo
      group (Minnesota Living with Heart Failure Questionnaire, 6 min walking test).
      Concomitantly, there was a trend towards increased left ventricular ejection
      fraction (radionuclear ventriculography) and improved endothelial function
      (forearm blood flow). Statins decreased plasma concentrations of troponine T,
      high sensitive C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI
      1) and tumor necrosis factor alpha (TNFalpha). CONCLUSIONS: Statins induce
      beneficial effects in patients with non-ischemic cardiomyopathy leading to
      improvement of quality of life and exercise capacity disclosing a promising novel
      treatment strategy for patients with heart failure.

PMID- 14963676
TI  - Alteration of heme-oxygenase-carbon monoxide pathway in calcified rat vascular
      smooth muscle cells.
AB  - OBJECTIVE: The aim of the present study was to investigate the changes in heme
      oxygenase (HO)-carbon monoxide (CO)-cyclic guanosine monophosphate (cGMP) pathway
      in clacified rat vascular smooth muscle cells (VSMCs). METHODS: Calcification of
      cultured rat VSMCs was induced by incubation of VSMCs with beta-glycerophosphate.
      Cellular calcium content, ALP activities and (45)Ca uptake were measured. HO
      activity, HbCO formation and content of cGMP in VSMCs were determined.
      Immunocytochemistry for HO-1 expression was observed. RESULTS: In comparison of
      control VSMCs, the cellular calcium content, ALP activity and (45)Ca uptake in
      calcified VSMCs were obviously increased. Immunocytochemistry showed that HO-1
      expression was weak and not well distributed in calcified cells as compared to
      non-calcified VSMCs, but interestingly, there was stronger staining in calcified
      nodules than in VSMCs. Compared with VSMCs, HO-1 activity in calcified cells
      decreased by 42.7% [36.4 +/- 2.8 pmol (mg Pr x h)(-1) vs 63.5 x 5.3 pmol (mg Pr x
      h)(-1), p < 0.01], and HbCO formation decreased by 39.2% (3.38 x 0.69 micromol/mg
      Pr vs 5.56 +/- 0.48 micromol/mg Pr, p < 0.05). The cGMP content in calcified
      VSMCs was 78.1% lower than that of non-calcified VSMCs (4.3 +/- 0.51 vs 19.6 +/-
      1.2 pmol/mg, p < 0.01). CONCLUSION: The results showed that HO-CO-cGMP pathway in
      calcified vascular cells obviously changed, which might contribute to disturbance
      of vascular function.

PMID- 14963677
TI  - [The technique of outflow tract reconstruction in patients with tetralogy of
      Fallot influence the morbidity 3 decades after repair].
AB  - The purpose of this study was to examine long-term results of different surgical
      techniques in patients with tetralogy of Fallot considering their morbidity. We
      analyzed the data of 74 patients 24.5 +/- 3 years after surgical repair in
      childhood to evaluate their clinical status, maximal exercise capacity,
      medication and frequency of reoperations. We compared two groups of patients
      according to the surgical techniques employed: 1) TAP group (Trans anular Patch,
      n = 41) in which ventricular septal defects were closed with a Dacron patch, the
      right ventricular outflow was reconstructed by resection of the partial extension
      of the infundibular septum and transanular patch repair was performed because of
      hypoplastic pulmonary valve. 2) nonTAP group (33) in which no transanular patch
      repair was necessary. Most of the patients described their health as "good". 94%
      of the nonTAP group and 71% of TAP group were in NYHA class I. The rest were in
      NYHA class II. Despite the good clinical classification we found a reduced
      cardiopulmonary exercise capacity in all patients. More than 50% in the TAP group
      took medicine because of congestive heart failure and/or arrhythmia, which was
      present 3-times more often compared with the nonTAP group. Furthermore, 50% of
      TAP group patients had at least one reoperation during the follow- up: by
      comparison 5-times more often than the nonTAP group. These data show that the
      long-term outcome and morbidity of the patients after repair is closely related
      to the type of the surgical technique employed.

PMID- 14963678
TI  - Expression and activity of matrix metalloproteinase-2 in calcific aortic
      stenosis.
AB  - Calcific aortic stenosis is the main heart valve disease in the elderly, leading
      to massive focal calcification and thickening of the valve cusps. Matrix
      metalloproteinases (MMPs) are thought to contribute to this process. Therefore,
      the study assessed the expression of the gelatinases MMP-2 and MMP-9 and the
      endogenous tissue inhibitor of metalloproteinase (TIMP)-2 as well as the
      gelatinolytic activity in normal and stenotic valves. Human tricuspid aortic
      valves with and without calcific aortic stenosis were studied by
      immunohistochemistry for MMP-2, MMP-9 and TIMP-2. The gelatinolytic activity in
      native valve sections was assessed by gelatin in situ zymography with or without
      addition of the MMP activator p-aminophenymercuric acetate (APMA). Staining
      intensities for MMP-2 and TIMP-2 were elevated in stenotic valves as compared to
      controls. Minor staining of MMP-9 was present exclusively in stenotic valves. The
      morphologic distribution of gelatinolytic activity was comparable to the staining
      pattern of MMP-2, and since MMP-9 immunostaining demonstrated only a low number
      of positive cells, the observed gelatinolytic activity is likely due to MMP-2.
      Gelatinolytic activity was low in normal valves but significantly increased by
      the MMP activator APMA. In contrast, stenotic valves showed a strong basal
      gelatinolytic activity that could not be significantly enhanced by APMA
      suggesting that MMP-2 is present as a latent pro-enzyme in normal valves and
      activated in stenotic valves. Thus, MMP-2 might be involved in the matrix
      remodeling during calcific aortic stenosis.

PMID- 14963679
TI  - [The PreFord Study. A prospective cohort study to evaluate the risk of a
      cardiovascular event (overall-collective) as well as a prospective, randomized,
      controlled, multicentre clinical intervention study (high-risk-collective) on
      primary prevention of cardiovascular diseases in the Ford Motor Company employees
      in Germany].
AB  - The PreFord Study is a multicenter prospective cohort study to evaluate guideline
      based risk management on primary prevention of cardiovascular diseases.
      Furthermore a randomised controlled trial (RCT) will be designed to analyse the
      effect of a special intervention program. 40,000 employees of the Ford Motor
      Company, Visteon Company and Deutz Company in Germany will be included, monitored
      for ten years and the following primary endpoints will be investigated: 1.
      evaluation and comparison of established and newly developed risk-scores, 2. the
      relative impact of single and combined cardiovascular risk factors on
      cardiovascular diseases, 3. the influence of a novel occupationally integrated
      ambulant rehabilitation program in combination with a guideline oriented optimal
      drug therapy within a high risk group on the primary endpoint: risk reduction by,
      4. the influence of this intervention on secondary endpoints: death, myocardial
      infarction and stroke, combined appearance of angina pectoris and
      hospitalisation, occurrence of cerebral circulatory disorder and hospitalisation,
      occurrence of peripheral occlusive arterial disease and hospitalisation and
      single cardiovascular risk factors and cost-benefit-analysis. Beginning with an
      cross sectional study there will be a systemic screening of cardiovascular risk
      profiles, of anthropometric data and different lifestyle-factors. Based on these
      data participants will be differentiated into three risk-groups according to the
      risk score of the European Society of Cardiology (risk of a lethal primary acute
      cardiovascular event: I < or = 1%; II > 1-< 5% and III > or = 5%). In the
      following longitudinal study different strategies will be applied: Group I: low
      risk (< 0.5% per year): repetition of the investigation after five and ten years.
      Group II: middle risk, (0.6% to 1.4% per year), repetition of the investigation
      every two years, instruction of the patients general practitioner (GP) with
      respect to a risk factor oriented and evidence based treatment. Group III: high
      risk, (> 1.5% per year or >15% within the next 10 years) will be randomised into
      two interventional groups. The first one, the intervention-group "PreFord" will
      perform an occupational integrated rehabilitation program (2,5-3 hours twice a
      week, for 15 weeks according to the BAR guidelines) with a following engagement
      in heart-groups and an annual repetition of the check-ups. The second group, the
      "classic" intervention-group will be treated evidence based in cooperation with
      their GP. As a result of this long term interventional study efficient, area wide
      implementable and economically feasible prevention concepts with special regards
      to operational healthcare will be developed and evaluated. Core elements will be
      exercise- and lifestyle-oriented concepts as well as guideline-based
      pharmacotherapy.

PMID- 14963680
TI  - [Clinical experiences with cooled radiofrequency ablation of ectopic atrial
      tachycardia employing an electroanatomic mapping system].
AB  - Due to its variable origin success for ablation of ectopic atrial tachycardia
      (EAT) has been difficult to achieve using conventional mapping and ablation
      strategies. In contrast, no information in the literature is available about the
      use of a nonfluoroscopic, 3-dimensional electroanatomic mapping system (CARTO)
      combined with the cooled ablation technology creating deeper lesions in
      experimental studies compared to standard catheters. In 20 consecutive patients
      (15 female; age 52.5 +/- 15.4 years), a single focus responsible for clinical EAT
      has been mapped. Twelve EATs were located in the right atrium, whereas 8 foci
      were left sided including 3 origins within a pulmonary vein (PV). Due to the
      reported development of PV stenosis in the ablative treatment of focal atrial
      fibrillation, direct ablation applied inside the PV was avoided. Instead, PV
      disconnection achieved by the use of a Lasso trade mark catheter in 1 case and by
      circumferential ablation around the PV in 2 other patients was preferred. In 2
      patients, ablation was not attempted because of an origin located directly in the
      area of the atrioventricular node. In another case, CARTO mapping was stopped due
      to persistent mechanical termination of the tachycardia with no possibility of
      reinduction. In the latter, ablation was performed in sinus rhythm at the
      earliest mapped site before terminating. Three weeks later another episode of EAT
      was noted in this patient. In the remaining 17 cases, ablation was associated
      with acute success and no recurrences of sustained tachycardia in all patients.
      Mean duration time was 192 +/- 53.3 min (right atrium 161 +/- 37.9 min; left
      atrium 229.6 +/- 46.2 min), and average fluoroscopic time was 22.8 +/- 9.7 min
      (right atrium 17.1 +/- 6.2 min; left atrium 29.8 +/- 8.9 min). There was no
      incidence of serious complications associated with this procedure. In
      conclusions, electroanatomical mapping including cooled ablation was a safe and
      feasible strategy in treating EATs. The benefit of this technique may imply the
      combination of both precise localization of the focus and effective applications
      of radiofrequency pulses, thereby minimizing acute failures or reablation. Due to
      the time consuming point by point data acquisition, the ability to generate
      precise maps demonstrating the earliest activation at their exact anatomical
      location can be limited by transient or persistent termination of the
      tachycardia.

PMID- 14963681
TI  - [Transcatheter closure of congenital ventricular septal defects].
AB  - We report on the transcatheter closure of ventricular septal defects (VSD) in 26
      patients with Amplatzer Occluders and Nit- Occlud Coil Systems. Twenty-one
      patients had a perimembranous and 5 patients a muscular VSD. Patients' age range
      was 5 months to 59 years (median 8 years) and their body weight 4.5 kg to 167 kg
      (median 28 kg). Defect diameters were 3-11 mm (median 5 mm). Sixteen patients had
      left ventricular volume overload and 7 patients pulmonary hypertension (median
      50% of systemic pressure). Seven patients suffered from trivial or mild aortic
      regurgitation. Twenty-eight devices (4-12 mm; median 8 mm) were implanted (16
      Amplatzer, 12 Nit-Occlud) through sheaths of 4F to 9F (median 7F). Fluoroscopy
      times were 8.3- 56.5 min (median 26.2 min). One coil was surgically explanted
      directly after intervention. One patient needed pulmonary banding due to
      additional VSDs. After a follow-up of 7 months (1-12 months), 2 patients had a
      small and 9 a minimal residual shunt. Thirteen defects were completely closed.
      Transcatheter closure of VSDs with new devices seems to be a promising therapy
      for suitable defects in different hemodynamic conditions in patients of every
      age.

PMID- 14963682
TI  - [Atypical acute myocardial ischemia syndrome with reversible left ventricular
      (LV) wall motion abnormalities ("apical ballooning") without significant coronary
      artery disease].
AB  - We report on three patients with acute myocardial ischemia syndrome, without
      significant coronary artery disease, who were admitted within one year in our
      hospital and presenting an atypical balloon-like, reversible left ventricular
      apical wall motion abnormality. The reported cases showed the following
      similarities: 1) elderly women (age >65 years), 2) triggered by physical or
      emotional stress, 3) dynamic reversible ST-T segment abnormalities and 4)
      positive troponin I. During a one year follow-up, all patients remained
      asymptomatic. As compared to the usual forms of the acute coronary ischemia
      syndrome, this syndrome showed a unique balloon-like left ventricular (LV) wall
      motion abnormality at the apex, which did not correlate with the coronary supply
      of a major coronary vessel. The etiology and pathophysiological basis of this
      coronary syndrome, which has previously been described in Japan, is still not
      well understood.

PMID- 14963683
TI  - Transcatheter PFO closure with a prominent Eustachian valve.
AB  - We report the successful PFO closure in a 57-year old woman with complex atrial
      anatomy. To avoid the risk of interfering with the occluder device due to a
      prominent Eustachian valve, a Helex Septal Occluder was implanted. Differential
      therapeutic considerations and specific device characteristics are outlined.

PMID- 14963685
TI  - The effect of experimental epilepsy induced by penicillin administration during
      pregnancy on nestin expression in the immature rat cerebellum. A light, electron
      microscopic, and immunohistochemical study.
AB  - INTRODUCTION: Recent knowledge regarding the effect of epileptic seizures in
      pregnant women on newborns was limited and, therefore, it was difficult to
      suggest the proper clinical guidelines and to take precautions against it.
      Studies evaluating the morphological effects of epileptic seizure during
      pregnancy on newborns in various experimental models are valuable. Therefore, the
      current study was designed to investigate the morphological changes in the
      cerebellum of newborn pups of rats subjected to experimental epilepsy during
      pregnancy. MATERIALS AND METHODS: Swiss Albino rats were divided into three
      groups (six animals in each). In the first group (experimental group) an acute
      grand mal epileptic seizure was induced by 400 IU penicillin-G administration
      into their intrahippocampal CA3 region with a stereotaxic device during the 13th
      day of their pregnancy. The second group (intrahippocampal saline-injected sham
      group) and the third group (untreated animals) were the control groups. On the
      1st neonatal day, pups were perfused with intracardiac fixative solution under
      anesthesia, and newborn cerebellums were dissected surgically for light and
      electron microscopic studies. RESULTS: In an immunohistochemical study using Rat
      401 monoclonal antibody and peroxidase, the intermediate filament nestin was
      detected in the developing cerebellar tissue. Histologically, normal migration
      and cerebellar maturation were determined in the newborn rat cerebellum in the
      control and sham-operated groups. It was observed that the morphological
      structure of the cerebellar cortex in the experimental group was compromised in
      the early embryonal period. In contrast to the control and sham groups, it was
      found that nestin (+) cell density was increased in the experimental epilepsy
      group. CONCLUSIONS: It has been concluded that epileptic convulsions during
      embryonic life may cause early neurogenesis and delayed maturation, which
      explains the harmful effects of epileptic grand mal seizures, hypoxia, and
      obstetric trauma to the embryo at the early stage of neuronal differentiation.
      However, further studies are necessary to investigate epileptic pregnant
      phenomena and to characterize the possible relationship between epilepsy and
      congenital malformations as well as mental retardation.

PMID- 14963686
TI  - Muenke syndrome.
AB  - BACKGROUND: Muenke syndrome is a genetically determined craniosynostosis that
      involves one or both coronal sutures. In some patients it is associated with
      skeletal abnormalities such as thimble-like middle phalanges, coned epiphysis,
      and/or neurological impairment, namely sensorineural hearing loss or mental
      retardation. In spite of a variable phenotype, Muenke syndrome has been related
      to a unique mutation on the FGFR3 gene, Pro 250 to Arg, which is characteristic
      of this disease. Because of the incomplete penetrance of this anomaly, the
      suspicion of Muenke syndrome must be raised in any child with uni- or bilateral
      coronal craniosynostosis, and the genetic analysis propounded even in the absence
      of extracranial features. ILLUSTRATIVE CASES: We report the cases of two sisters
      who presented with Muenke syndrome and whose affected mother did not have any
      form of craniosynostosis.

PMID- 14963687
TI  - In vivo-application of anti-proctolin-antiserum affects antennal flight posture
      in crickets.
AB  - Tethered crickets flying in a wind tunnel adopt a characteristic posture in which
      the antennae are pointed in parallel and anteriorly into the headwind. Although
      the firing rates of antennal motoneurons are largely reduced after the start of a
      flight sequence, the associated postural changes of the antennae are small. It is
      hypothesised that proctolin, which is present in antennal motoneurons, stabilises
      the prolonged antennal forward position. To test this hypothesis, proctolin was
      blocked by anti-proctolin antiserum injections into one antennal base in
      otherwise intact behaving crickets. The antiserum quickly led to prolonged
      backward deflections of the treated antennae in 65% of cases. It then took more
      than one hour for the deflected posture to revert to a normal flight posture. It
      appears that proctolin is necessary to produce muscle tension large enough to
      hold the antennae in a forward position and to compensate for the headwind drag.
      Proctolin, therefore, acts to generate force with reduced electrical activity of
      motoneurons and muscles.

PMID- 14963688
TI  - Main splenic artery embolization using coils in blunt splenic injuries: effects
      on the intrasplenic blood pressure.

PMID- 14963689
TI  - Factors influencing accuracy of CT-guided percutaneous biopsies of pulmonary
      lesions.
AB  - The purpose of this study was to evaluate the performance and complication rate
      of CT-guided percutaneous lung biopsy of pulmonary lesions using a coaxial
      automated biopsy device and to determine factors influencing the false negative
      rate for the diagnosis of malignancy. A prospective study of 605 consecutive
      biopsies performed in 595 patients was undertaken. The performances for the
      diagnosis of malignancy, for the specific diagnosis of benignity and the
      complication rate were calculated. Patients' characteristics and lesion and
      procedure variables were included in a logistic regression model and analyzed as
      potential predictive variables for occurrence of a false-negative diagnosis of
      malignancy. The sensitivity, specificity, positive predictive value and negative
      predictive value for a diagnosis of malignancy were 92.2, 99.1, 99.8 and 73.3%,
      respectively. A specific diagnosis of benignity was obtained in 43 cases (40%)
      biopsies. The pneumothorax rate was 17.4% (n = 105) with 3 (0.5%) requiring
      drainage. At multivariate analysis, the sole variable significantly associated
      with a higher rate of false negative diagnosis of malignancy was lesion size
      equal to or smaller than 10 mm in diameter. Using a coaxial automated device, CT
      guided percutaneous biopsy of pulmonary lesions of size equal to or less than 10
      mm in diameter provides a high diagnostic yield with an acceptable complication
      rate.

PMID- 14963690
TI  - The root: a potential new source of competent cells for high-frequency
      regeneration in Tylophora indica.
AB  - The purpose of this study was to develop a new micropropagation system for
      Tylophora indica, an important medicinal plant in India, using root explants as
      starting material. Root explants cultured on MS medium supplemented with 6
      benzyladenine (BA) or 2-isopentyladenine (2iP) produced organogenic nodular
      meristemoids (NMs) within 4 weeks. NMs induced from the cut ends of root segments
      showed two types of organogenic response--direct shoot bud formation and somatic
      embryogenesis--when maintained on induction medium. In 42% of the explants, NMs
      developed shoot buds directly in the presence of 10.72-26.80 microM BA. On
      average, 18.5 +/- 0.7 shoots per gram of NM tissue were obtained after each 4
      week subculture. Elongation of microshoots and root initiation were correlated
      with the auxin used, with the optimal response occurring in the presence of 28.54
      microM indole-3-acetic acid. In 39% of the explants, NMs dedifferentiated into
      friable embryogenic callus (FEC) in the presence of BA or 2iP after 12 weeks of
      culture. Of the different treatments, MS medium supplemented with 10.72 microM BA
      was the most effective in inducing FEC and somatic embryogenesis: at this
      concentration 64% of the cultured NMs developed FEC and, on the same medium, 89%
      of the FEC produced globular somatic embryos (SEs). FEC biomass increased nearly
      five-fold with every 4-week subculture, and about 30 SEs were recovered per gram
      of FEC during this period. The best conversion of mature SEs to complete
      plantlets was obtained on basal MS medium-42%. Plantlets derived via somatic
      embryogenesis and shoot organogenesis were successfully hardened (88-96%) and
      transferred to the field.

PMID- 14963691
TI  - Modification of senescence in ryegrass transformed with IPT under the control of
      a monocot senescence-enhanced promoter.
AB  - We report here the genetic modification of ryegrass senescence. Embryogenic cell
      suspensions of Lolium multiflorum were transformed by microprojectile bombardment
      with plasmid constructs containing 1.98 kb of the 5' flanking sequence of SEE1 (a
      maize cysteine protease gene showing enhanced expression during senescence) fused
      either to the Agrobacterium tumefaciens cytokinin biosynthesis gene IPT
      (designated PSEE1::IPT) or to the beta-glucuronidase reporter gene UIDA
      (PSEE1::UIDA). Plants were regenerated under selection for the HPH hygromycin
      resistance gene in the vector. PSEE1::UIDA transformants confirmed that the SEE1
      flanking sequence functioned as a senescence-enhanced promoter in ryegrass. The
      IPT transgene was detected in 28 regenerants (PSEE1::IPT) from five independent
      transformation events. PSEE1::IPT leaves displayed a stay-green phenotype. Some
      PSEE1::IPT lines developed spontaneous lesions.

PMID- 14963692
TI  - Plant regeneration from hairy-root cultures transformed by infection with
      Agrobacterium rhizogenes in Catharanthus roseus.
AB  - Hypocotyl explants of Catharanthus roseus produced hairy roots when cultured on
      Murashige and Skoog (MS) basal medium after infection by Agrobacterium
      rhizogenes. Explants gave rise to adventitious shoots at a frequency of up to 80%
      when cultured on MS medium supplemented with 31.1 microM 6-benzyladenine and 5.4
      microM alpha-naphthaleneacetic acid. There was a significant difference in the
      frequency of adventitious shoot formation for each hairy-root line derived from a
      different cultivar. Plants derived from hairy roots exhibited prolific rooting
      and had shortened internodes. Approximately half of the plants had wrinkled
      leaves and an abundant root mass with extensive lateral branching, but otherwise
      appeared morphologically normal. Plants with hairy roots that were derived from
      the cultivar Cooler Apricot developed flowers with petals that were white in the
      proximal region, whereas the wild-type flower petals are red. PCR and Southern
      blot analyses revealed that plants derived from hairy roots retained the Ri TL
      DNA.

PMID- 14963693
TI  - The moss Physcomitrella patens releases a tetracyclic diterpene.
AB  - The presence of the tetracyclic diterpene 16alpha-hydroxykaurane (16alpha-hydroxy
      ent-kaurane, C20H34O, CAS 5524-17-4) was detected in sterile cell cultures of the
      moss Physcomitrella patens (Hedw.) B.S.G. using gas chromatography and mass
      spectrometry. 16alpha-hydroxykaurane was found to be a major lipid compound in P.
      patens, with an estimated intracellular concentration of up to 0.84 mmol/l and an
      extracellular concentration of up to 9.3 micromol/l. The overall content of
      16alpha-hydroxykaurane (in milligrams) produced per culture reached 0.37-fold
      that of chlorophyll a+b. In agar cultures with low air exchange, 16alpha
      hydroxykaurane forms needle-like crystals on tissue and on the inner surface of
      the culture vessels, indicating that it is being released into the atmosphere.
      Solid phase microextraction confirmed the air-bound release of 16alpha
      hydroxykaurane. To our knowledge this is the first report on the release of a
      plant-derived tetracyclic diterpene into the air.

PMID- 14963694
TI  - Long-term evaluation of lung function in patients affected by scleroderma treated
      with cyclic iloprost infusions.
AB  - OBJECTIVE: The aim of this study was to evaluate pulmonary function in patients
      suffering from scleroderma treated for 3 years with cyclic iloprost infusions.
      METHODS: Thirty patients affected by scleroderma (five men and 25 women, mean age
      49.3 years, mean disease duration 8 years, 19 with limited and 11 with diffuse
      disease patterns) were treated for 5 consecutive days every 4 months for 3 years
      with iloprost. Pulmonary function was evaluated at baseline and after 3 years. At
      the end of the trial, color Doppler echocardiography was performed in 26 of the
      patients. RESULTS: Spirometric parameters did not significantly change after 3
      years of therapy when expressed as percentage of the predicted normal value.
      Diffusing lung capacity for carbon monoxide decreased at the limit of statistical
      significance. No patients developed clinical pictures suggestive of severe
      pulmonary arterial hypertension, which was confirmed in 26 subjects by evaluation
      of estimated pulmonary artery systolic pressure. CONCLUSIONS: This long-term
      study showed that lung function remained substantially stable after 3 years of
      treatment with cyclic iloprost infusions. No cases of severe pulmonary
      hypertension were observed.

PMID- 14963695
TI  - The effects of colchicine and hydroxychloroquine on the cyclo-oxygenases COX-1
      and COX-2.
AB  - OBJECTIVE: The aim of this study was to test whether colchicine and
      hydroxychloroquine have an inhibitory effect on cyclo-oxygenases (COX). METHODS:
      Measurement of COX-1 and COX-2 activity was performed by using whole blood assay.
      Serum thromboxane (TXA) and plasma prostaglandin 2 (PGE2) levels were determined
      using a commercially available enzyme immunoassay kit. Celecoxib, etodolac, and
      nimesulide were also tested as controls. Since the study was intended to find a
      qualitative effect rather than a quantitative relationship between the drugs and
      the enzymes, we used higher concentrations than the therapeutic range. RESULTS:
      Colchicine did not have an inhibitory effect on cyclo-oxygenases.
      Hydroxychloroquine had a mild inhibitory effect in a relatively high
      concentration. As expected, celecoxib, etodolac, and nimesulide did have an
      inhibitory effect on the cyclo-oxygenases. CONCLUSIONS: Neither colchicine nor
      hydroxychloroquine exert their anti-inhibitory effect through inhibition of cyclo
      oxygenases.

PMID- 14963696
TI  - Hepatitis C virus-associated thrombocytopenia: a controlled prospective,
      virological study.
AB  - Chronic hepatitis C virus (HCV) infection has also been associated with the
      development of several extrahepatic alterations, including thrombocytopenia, and
      a variety of pathogenic mechanisms are reported to be implicated in this
      hematological abnormality. Different studies have succeeded in detecting HCV in
      platelets with discrepant results. Moreover, most of the studies on HCV
      associated thrombocytopenia have failed to provide data concerning the infecting
      genotype, a factor with prognostic implication in chronically HCV-infected
      patients. To determine whether thrombocytopenia is an extrahepatic alteration
      dependent on particular HCV genotypes, and to assess the relationship between
      thrombocytopenia and detection of HCV-RNA (positive strand) in platelets from
      patients with chronic HCV infection, 106 anti-HCV+/HCV-RNA+ patients (57
      thrombocytopenic and 49 non-thrombocytopenic) were prospectively studied. The
      infecting genotype was analyzed from sera by using direct nucleotide sequencing
      of the polymerase chain reaction (PCR) products from core region. Genotypes 1a,
      1b, and 3a were more prevalent in our patients, and no association between these
      genotypes and thrombocytopenia was observed ( p=0.891). HCV-RNA was detected in
      platelets by reverse transcriptase (RT)-nested PCR in the 5' non-coding region
      with a higher frequency (60%) in thrombocytopenic patients than in non
      thrombocytopenic subjects (35%, p=0.017), suggesting that HCV is directly
      involved in the process that, at least in part, leads to thrombocytopenia.

PMID- 14963697
TI  - Synchronous occurrence of breast carcinoma and acute myeloid leukemia: case
      report and review of the literature.
AB  - We present a case of breast carcinoma, which was followed by acute leukemia
      within 1 month of diagnosis of the former. She had undergone a modified radical
      mastectomy for her breast cancer and had not received chemotherapy or
      radiotherapy. Acute leukemia as a result of chemotherapy for breast carcinoma is
      well known. However, patients developing synchronous breast carcinoma and acute
      leukemia, in the absence of any chemotherapy or radiotherapy, are rare.

PMID- 14963698
TI  - The clinical relevance of thymic fluorodeoxyglucose uptake in pediatric patients
      after chemotherapy.
AB  - The purpose of this study was to clarify the clinical implications of thymic
      fluorodeoxyglucose (FDG) uptake after chemotherapy in pediatric patients with
      malignant disease. Twenty-two pediatric patients, aged 0-17 years (mean 7.0
      years), who had undergone FDG positron emission tomography (PET) were examined
      retrospectively. A total of 48 FDG-PET scans of the 22 patients were reviewed.
      Seven PET scans were recorded before the initial chemotherapy, and the remaining
      41 scans were conducted during and after chemotherapy. Thymic FDG uptake was
      evaluated using standardized uptake value (SUV) analysis. The effect of
      chemotherapy on thymic FDG uptake was assessed by comparing SUV before, during,
      and after chemotherapy. The change in thymic FDG uptake with increasing time
      after the completion of chemotherapy was also assessed. Clinical laboratory data
      including number of white blood cells (WBCs), erythrocytes (RBCs), platelets,
      plasma glucose level and differential white blood count were analyzed for their
      association with thymic FDG uptake. Thymic FDG uptake in patients during
      chemotherapy was significantly lower than that in patients before chemotherapy
      (mean+/-SD 1.71+/-0.48 vs 2.27+/-0.32, respectively, P<0.01). Thymic FDG uptake
      in patients after chemotherapy was significantly higher than that in patients
      during chemotherapy (mean+/-SD 2.74+/-0.70 vs 1.71+/-0.48, respectively, P<0.01).
      A significant relationship between thymic FDG uptake and interval after
      completion of chemotherapy (r=0.74, P<0.0001) was observed. Significant
      relationships between blood counts (WBCs, RBCs, and platelets) and thymic FDG
      uptake were also observed. Comparison of the differential white blood count and
      thymic FDG uptake revealed a significant relationship only with lymphocyte count.
      Thymic FDG uptake in pediatric patients after completion of chemotherapy should
      not be mistaken as recurrent or metastatic thymic malignancy. Thymic FDG uptake
      appears to be associated with thymic function or hematopoietic function in bone
      marrow. Interpretation of FDG-PET must be made with this consideration in mind.

PMID- 14963699
TI  - 99mTc-EDDA/HYNIC-TOC scintigraphy in oncological diagnostics: methodological
      considerations-reply.

PMID- 14963700
TI  - Androgen receptor (AR) expression is an independent unfavorable prognostic factor
      in gastric cancer.
AB  - PURPOSE: To investigate the expression of sex steroid receptors in gastric cancer
      and to correlate their tumor expression profile with the clinicopathological
      parameters and overall survival of the patients. METHODS: Immunohistochemical
      methodology was employed in formalin-fixed paraffin-embedded sections from 86
      patients with gastric carcinoma. Monoclonal antibodies against androgen (AR),
      estrogen (ER), and progesterone (PR) receptors were used. Survival rates were
      estimated by the Kaplan-Meier method and compared using the log-rank test.
      Multivariate analysis was performed by the Cox proportional hazards model.
      RESULTS: Fifteen (17.4%) cases of gastric adenocarcinomas were positive for AR,
      two (2.3%) were positive for PR and three (3.5%) were positive for ER.
      Significantly higher AR expression was found in tumors with metastases to lymph
      nodes (P = 0.03). Patients with AR-positive tumors (AR+) had worse prognosis than
      (AR-) patients (median survival 9 months vs 24 months, P = 0.03). Patients with
      AR- and heat shock protein 27 (HSP27)-positive tumors (AR+/HSP27+) had a median
      survival of 6 months, whereas (AR-/HSP27-) patients had a median survival of 42
      months (P = 0.017). Multivariate analysis revealed that AR expression and UICC
      stage were independent factors of unfavorable prognosis (P = 0.037 and P =
      0.0055, respectively). CONCLUSIONS: Identification of AR-positive gastric
      carcinomas in gastric biopsies may warrant a more aggressive therapeutic approach
      and anti-androgen or AR-targeted agents may represent a novel strategy in
      tackling this devastating malignancy.

PMID- 14963701
TI  - The wandering spleen: something to bear in mind in the presence of a mobile
      abdominal mass.

PMID- 14963702
TI  - Efficacy of intravenous immune globulin therapy combined with dexamethasone for
      the initial treatment of acute Kawasaki disease.
AB  - We studied the effects of a new regimen consisting of intravenous immune globulin
      (IVIG) combined with dexamethasone (DEX) on clinical outcome and serum levels of
      vascular endothelial growth factor (VEGF) in the initial treatment of Kawasaki
      disease (KD). A total of 46 KD patients received 0.3 mg/kg per day DEX plus
      heparin i.v. for 3 consecutive days, together with 2 g/kg IVIG over 4 to 5 days
      (DEX group). Low-dose acetylsalicylic acid was started after completion of DEX
      therapy. The control group consisted of 46 KD patients retrospectively treated
      earlier with 2 g/kg IVIG over 4 to 5 days plus higher dose acetylsalicylic acid
      (CONTROL group). No serious adverse effect was noted in either group. There were
      no differences in baseline and post-treatment laboratory data except for C
      reactive protein between the groups. Post-treatment C-reactive protein in the DEX
      group (median 0.9 mg/dl, range 0.0 to 24.7 mg/dl) was lower than that (1.2 mg/dl,
      range 0.2 to 19.5 mg/dl) in the CONTROL group ( P=0.033 by Mann-Whitney U test).
      In addition, the mean duration of fever after the first IVIG infusion was 2.2
      days (median 1 day, range 1 to 12 days) in the DEX group and 2.8 days (2 days, 1
      to 16 days) in the CONTROL group ( P=0.015 by Mann-Whitney U test). The new
      regimen did not reduce VEGF levels. Two patients in each group developed small-
      or medium-sized coronary artery aneurysms. CONCLUSION: Although this regimen did
      not affect coronary outcome, intravenous immune globulin therapy combined with
      dexamethasone for the initial treatment of Kawasaki disease was safe and may
      accelerate the resolution of systemic inflammation.

PMID- 14963703
TI  - Severe mucous membrane involvement in epidermolysis bullosa simplex with muscular
      dystrophy due to a novel plectin gene mutation.
AB  - Epidermolysis bullosa simplex with muscular dystrophy (OMIM 226670) is an
      autosomal recessive disorder caused by mutations of the human plectin gene on
      chromosome 8q24. Here, we report a 3-year-old girl, offspring of a consanguineous
      Lebanese family, who presented with skin blistering and recurrent episodes of
      severe respiratory distress necessitating tracheotomy at the age of 2 years.
      Repeated examination did not provide any evidence of muscle involvement. Indirect
      immunofluorescence analysis of a diagnostic skin biopsy with four different
      domain specific plectin antibodies showed a complete absence of plectin staining.
      Mutation analysis revealed a novel homozygous single guanine insertion mutation
      (5588insG/5588insG) residing in the N-terminal part of exon 31 of the plectin
      gene. CONCLUSION: The complete lack of protein expression, which may be
      attributed to a nonsense-mediated plectin mRNA decay, is likely to cause muscular
      dystrophy and other multisystem involvement later in life.

PMID- 14963704
TI  - Altered expression of GFLO, the Gesneriaceae homologue of FLORICAULA/LEAFY, is
      associated with the transition to bulbil formation in Titanotrichum oldhamii.
AB  - Titanotrichum oldhamii inflorescences switch from flower to bulbil production at
      the end of the flowering season. The structure of the bulbiliferous shoots
      resembles the abnormal meristematic organization of the Antirrhinum mutant,
      floricaula. Gesneriaceae- FLORICAULA (GFLO) is thus a candidate gene in the
      regulation of bulbil formation. To investigate this hypothesis, part of the GFLO
      gene (between the second and third exon) was isolated using degenerate primers
      designed in regions conserved between Antirrhinum, Nicotiana and Arabidopsis,
      followed by genome walking to obtain the complete gene and flanking sequences. RT
      PCR results showed that the GFLO homologue is strongly expressed in inflorescence
      apical meristems and young flowers. However, in meristems that had switched to
      bulbil formation, GFLO transcription was greatly reduced. The down-regulation of
      GFLO in bulbil primordia indicates that this gene is connected to, or part of,
      the bulbil-flower regulatory pathway. Phylogenetic analysis confirms the
      orthology of GFLO and FLO, and indicates that the gene may be useful for
      phylogenetic reconstruction at the genus or family level.

PMID- 14963705
TI  - Formation of unidentified nitrogen in plants: an implication for a novel nitrogen
      metabolism.
AB  - Plants take up inorganic nitrogen and store it unchanged or convert it to organic
      forms. The nitrogen in such organic compounds is stoichiometrically recoverable
      by the Kjeldahl method. The sum of inorganic nitrogen and Kjeldahl nitrogen has
      long been known to equal the total nitrogen in plants. However, in our attempt to
      study the mechanism of nitrogen dioxide (NO(2)) metabolism, we unexpectedly
      discovered that about one-third of the total nitrogen derived from (15)N-labeled
      NO(2) taken up by Arabidopsis thaliana (L.) Heynh. plants was converted to
      neither inorganic nor Kjeldahl nitrogen, but instead to an as yet unknown
      nitrogen compound(s). We here refer to this nitrogen as unidentified nitrogen (
      UN). The generality of the formation of UN across species, nitrogen sources and
      cultivation environments for plants has been shown as follows. Firstly, all of
      the other 11 plant species studied were found to form the UN in response to
      fumigation with (15)NO(2). Secondly, tobacco ( Nicotiana tabacum L.) plants fed
      with (15)N-nitrate appeared to form the UN. And lastly, the leaves of naturally
      fed vegetables, grass and roadside trees were found to possess the UN. In
      addition, the UN appeared to comprise a substantial proportion of total nitrogen
      in these plant species. Collectively, all of our present findings imply that
      there is a novel nitrogen mechanism for the formation of UN in plants. Based on
      the analyses of the exhaust gas and residue fractions of the Kjeldahl digestion
      of a plant sample containing the UN, probable candidates for compounds that bear
      the UN were deduced to be those containing the heat-labile nitrogen-oxygen
      functions and those recalcitrant to Kjeldahl digestion, including organic nitro
      and nitroso compounds. We propose UN-bearing compounds may provide a chemical
      basis for the mechanism of the reactive nitrogen species (RNS), and thus that
      cross-talk may occur between UN and RNS metabolisms in plants. A mechanism for
      the formation of UN-bearing compounds, in which RNS are involved as
      intermediates, is proposed. The important broad impact of this novel nitrogen
      metabolism, not only on the general physiology of plants, but also on plant
      substances as human and animal food, and on plants as an integral part of the
      global environment, is discussed.

PMID- 14963706
TI  - Control of nitrate reductase by circadian and diurnal rhythms in tomato.
AB  - Nitrate reductase (NR, EC 1.6.6.1) is a key regulatory enzyme in the assimilation
      of nitrate into amino acids in plant leaves. NR activity is intricately
      controlled by multifarious regulatory mechanisms acting at different levels
      ranging from transcription to protein degradation. It is among the few enzymes
      known to have a robust circadian rhythm of enzyme activity in many plant species.
      Although many aspects of NR regulation have been studied in depth, how these
      different types of control interact in a plant to deliver integrated control of
      activity in leaves over the course of the day has not been systematically
      investigated. This work documents that NR in young tomato (Lycopersicon
      esculentum Mill.) leaves has an endogenous rhythm in mRNA and protein level,
      which in nearly all circumstances are in phase with the rhythm in NR enzyme
      activity. Our data show that the diurnal control of NR activity in tomato leaves
      rests primarily with circadian regulation of Nia gene expression. The
      accompanying oscillations in protein level in tomato are made possible by a short
      half-life of NR protein that is approx. 6 h under normal conditions and approx.
      2.5 h when plants are darkened during mid-day. NR post-transcriptional regulation
      via phosphorylation and subsequent 14-3-3 protein binding has a physiologically
      vital but secondary regulatory role in tomato of rapidly deactivating NR in
      response to changes in light intensity that cannot be anticipated by circadian
      timing. The post-translational reactivation of phosphorylated NR appears to have
      its primary physiological role in tomato leaves in reversing the down regulation
      of NR following transient shading events. Although there is a significant steady
      state pool of apparently inactive NR throughout the diurnal, our data indicate
      that tomato leaves are unable to draw on this reserve to compensate for NR
      protein that is degraded during shading.

PMID- 14963707
TI  - Regulation of developmental pathways in cultured microspores of tobacco and
      snapdragon by medium pH.
AB  - The regulation of developmental pathways in cultured microspores of tobacco (
      Nicotiana tabacum L) and snapdragon ( Antirrhinum majus L) by medium pH is
      described for the first time. Unicellular tobacco and snapdragon microspores
      developed into normal, fertile pollen when cultured in media T1 and AT3 at pH 7.0
      and 25 degrees C for 6 and 8 days, respectively. First, pollen mitosis was
      asymmetric and mature pollen grains were filled with starch granules and
      germinated upon transfer to a germination medium. However, when tobacco and
      snapdragon microspores were cultured in media T1 and AT3, respectively, at pH 8.0
      8.5 for 4-6 days at 25 degrees C, the frequency of symmetric division increased
      significantly with the formation two nuclei of equal size, and the gametophytic
      pathway was blocked, as seen by the lack of starch accumulation and the
      inhibition of pollen germination. The transfer of these microspores to
      embryogenesis medium AT3 at pH 6.5 resulted in the formation of multicellular
      structures in both species and, in tobacco, in the formation of embryos and
      plants. In order to understand the possible mechanisms of the action of high pH,
      sucrose metabolism was analysed in isolated microspores of tobacco cultured at
      various pH values. Invertase (EC 3.2.1.26) activity in microspores was maximal at
      pH 5.0 and strongly decreased at higher pH, leading to a slow-down of sucrose
      cleavage. At the same time the incorporation of (14)C-labelled sucrose from the
      medium into microspores was drastically reduced at high pH. These data suggest
      that isolated microspores are not able to metabolise carbohydrates at high pH and
      thus undergo starvation stress, which was shown earlier to block the gametophytic
      pathway and trigger sporophytic development.

PMID- 14963708
TI  - The photomorphogenesis-related mutant red1 is defective in CYP83B1, a red light
      induced gene encoding a cytochrome P450 required for normal auxin homeostasis.
AB  - Previous genetic analysis identified a component, RED1, that is required for
      normal de-etiolation of Arabidopsis thaliana (L.) Heynh. seedlings in continuous
      red light (Rc). red1 mutant seedlings exhibit elongated hypocotyls and reduced
      cotyledon size specifically in Rc and not in continuous far-red light (FRc).
      Here, we show that red1 is allelic to sur2 and atr4, and is defective in the
      cytochrome P450 CYP83B1, an enzyme required for normal auxin homeostasis. Two
      alleles of atr4, like red1, exhibit increased hypocotyl elongation and reduced
      cotyledon expansion in Rc but not in FRc. We further show that CYP83B1 transcript
      levels are elevated specifically in Rc-grown seedlings when compared with
      seedlings grown in darkness or FRc. Hence, the Rc-specific phenotype of the red1
      mutant may indicate that Rc-induction of the CYP83B1 transcript is necessary for
      normal seedling de-etiolation in the wild type.

PMID- 14963709
TI  - Class-1 hemoglobins, nitrate and NO levels in anoxic maize cell-suspension
      cultures.
AB  - Nitric oxide (NO) is a reactive gas involved in many biological processes of
      animals, plants and microbes. Previous work has demonstrated that NO is formed
      during hypoxia in alfalfa ( Medicago sativa L.) root cultures and that the levels
      of NO detected are inversely related to the levels of expression of class-1
      hemoglobin expressed in the tissue. The objectives of this study were: to examine
      whether NO is produced in transgenic maize ( Zea mays L.) cell-suspension
      cultures exposed to anoxic growth conditions; to determine whether a similar
      relationship existed between a class-1 hemoglobin and the amount of NO detected
      under these conditions; and, to estimate the route of formation and breakdown of
      NO in the tissue. Maize cell-suspension cultures, transformed to express the
      sense or antisense strands of barley hemoglobin were used to overexpress or
      underexpress class-1 hemoglobin. A maize cell-suspension culture transformed with
      an empty vector was used as a control. Up to 500 nmol NO (g FW)(-1) was detected
      in maize cells exposed to low oxygen tensions for 24 h. The steady-state levels
      of NO in the different cell lines under anoxic conditions had an inverse
      relationship to the level of hemoglobin in the cells. There was no detectable NO
      produced under aerobic growth conditions. Spectroscopic data demonstrated that
      recombinant maize hemoglobin reacted with NO to form methemoglobin and NO(3)(-).
      Nitrate was shown to be a precursor of NO in anoxic maize cell-suspension
      cultures by using (15)NO(3)(-) and electron paramagnetic resonance spectroscopy,
      suggesting that NO is formed via nitrate reductase during hypoxia. The results
      demonstrate that NO is produced in plant tissues grown under low oxygen tensions
      and suggest that class-1 hemoglobins have a significant function in regulating NO
      levels.

PMID- 14963710
TI  - Voltage-dependent inhibition of rat skeletal muscle sodium channels by
      aminoglycoside antibiotics.
AB  - Aminoglycoside (AG) antibiotics interact with numerous biological molecules,
      including some voltage-gated ion channels. The present study demonstrates that
      4,5-disubstituted (neomycin class) and 4,6-disubstituted (kanamycin class) AGs
      inhibit whole-cell currents through cloned rat skeletal muscle sodium channels
      (mu1, Na(V)4.1). Increases in the amplitude of the step command reduced
      inhibition by extracellular AGs but increased inhibition by intracellularly
      applied AGs, indicating that the block was voltage dependent. Furthermore,
      intracellular neamine or sisomycin hastened the rate of macroscopic current decay
      at positive voltages. Extracellular solution containing sodium ions slowed the
      rate of current decay in the presence of intracellular sisomycin and decreased
      the apparent affinity of sisomycin from the intracellular side twofold. Current
      inhibition by extracellularly or intracellularly applied AGs was well fitted by
      the Woodhull model of pore block. The model indicated that most extracellularly
      applied AGs interact at a site that is an electrical distance of approximately 10
      15% from the outside, whereas intracellularly applied neamine or sisomycin bind
      to sites that are approximately 49% and approximately 24%, respectively, into the
      electric field from the inside. Our data suggested that AG antibiotics induce a
      low-affinity, voltage-dependent block of mu1 channels.

PMID- 14963711
TI  - Insulin enhances L-dopa renal proximal tubule uptake: a regulatory mechanism
      impaired in insulin resistance.
AB  - A stimulatory role for insulin in the uptake of neutral amino acids has been
      reported for a variety of tissues. Here we examine the effect of insulin on L
      dopa uptake by proximal tubule cells (PT cells) isolated from control and
      fructose-fed rats (FR-rats, 10% w/v fructose solution in tap water), a model of
      insulin resistance. Insulin (200 microU/ml) increased L-dopa uptake into PT cells
      by about 50% (705+/-186 vs.1117+/-140 pmol L-dopa/mg protein per minute)
      (p<0.05). The higher uptake correlated with a 40% increase in the number of high
      affinity L-dopa transport sites (L-dopa 0.2 microM) (0.59+/-0.05 vs. 0.82+/-0.09
      pmol L-dopa/mg protein per minute), without changing their affinity. The effect
      of insulin was not modified by ouabain (1 mM), nocodazole (1-10 microM) or
      colchicine (50-100 microM), whereas it was abolished by cytochalasin D or
      latrunculin B (both 1 microM). This suggests that the process is independent of
      Na(+),K(+)-ATPase activity or the microtubule network but that it requires the
      integrity of the actin cytoskeleton. L-dopa transport by the low-affinity
      transport sites (L-dopa 5 microM) was not affected by insulin, neither was the
      effect of insulin observed in PT cells isolated from FR-rats. In line with this,
      FR-rats showed lower renal L-dopa reabsorption as compared to control animals
      (81+/-4 vs. 51+/-9%). Taken together, our results support the involvement of
      insulin in the multifactorial regulation of renal L-dopa reabsorption.

PMID- 14963712
TI  - Yucheng: health effects of prenatal exposure to polychlorinated biphenyls and
      dibenzofurans.
AB  - Yucheng ("oil-disease") victims were Taiwanese people exposed to polychlorinated
      biphenyls (PCBs) and their heat-degradation products, mainly polychlorinated
      dibenzofurans (PCDFs), from the ingestion of contaminated rice oil in 1978-1979.
      Serial studies in Yucheng offspring born between 1978 and 1992 are summarized.
      Children of the exposed women were born with retarded growth, with dysmorphic
      physical findings, and, during development, with delayed cognitive development,
      increased otitis media, and more behavioral problems than unexposed children.
      Recently, examination of the reproductive system has suggested that prenatal
      exposure exerts late effects on semen parameters in young men after puberty.
      Results of the investigation in Yucheng children will provide important
      information about the human health effects and toxicology of PCB/PCDF exposure.
      Prenatal exposure to these environmental chemicals causes the fetus to be
      sensitive to the toxic effects of persistent organic pollutants.

PMID- 14963713
TI  - Cell type-specific and developmentally regulated expression of the AE1 anion
      exchanger in the chicken chorioallantoic membrane.
AB  - Antibodies specific for the chicken AE1 anion exchanger have been used to
      determine the cell-type specific pattern of expression of this electroneutral
      transporter in the chick chorioallantoic membrane (CAM) during embryonic
      development. Immunolocalisation analyses demonstrated that the AE1 anion
      exchanger accumulated in the basolateral membrane of a subset of cells in both
      the chorionic and allantoic epithelial layers. Double immunostaining indicated
      that the AE1-positive cells in the chorionic and allantoic epithelia were also
      positive for the carbonic anhydrase isoform, CAII, which serves as a marker for
      the villus cavity (VC) cells of the chorionic epithelium and the mitochondria
      rich cells of the allantoic epithelium. Immunoelectron microscopy revealed that
      AE1 accumulated in extensive projections that extended from the lateral membrane
      of VC cells towards the adjacent capillary covering cells. These results
      represent the first demonstration of anion exchanger expression in the chick CAM,
      and they suggest a role for basolateral AE1 in bicarbonate reabsorption that is
      required in the embryo for maintaining acid-base balance during development.

PMID- 14963714
TI  - Histochemical, ultrastructural, and three-dimensional observation of smooth
      muscle cells in human gastric mucosa.
AB  - The present study was undertaken to clarify the histochemical and ultrastructural
      properties and the three-dimensional distribution of the smooth muscle cells
      (SMCs) located in the lamina propria (LP) of the human gastric mucosa. Standard
      paraffin sections obtained from stomachs surgically resected for gastric cancer
      were immunostained for alpha-smooth muscle actin (alpha-SMA), vimentin, desmin,
      laminin, and type IV collagen. In addition, 100-microm-thick sections were
      fluorostained for alpha-SMA and CD34, while three-dimensional images were
      prepared by confocal laser scanning microscope. Ultrastructural studies were
      carried out using normal gastric biopsy specimens. The results indicated that
      SMCs in the LP differed between the upper and lower regions, SMCs in the lower LP
      being fairly typical SMCs, whereas those in the upper LP had apparently lost
      reactivity for desmin but gained that for vimentin. The basal lamina became
      sparser, but a fibronexus was occasionally seen in SMCs in the upper LP. Three
      dimensional images revealed bundles of SMCs in the upper LP encircling several
      foveolae to form acinus-like structures and, in the upper LP, SMCs branching into
      fine fibrils with a brush-like (corpus) or besom-like (i.e., a twiggy "witch's
      broom") appearance (antrum).

PMID- 14963715
TI  - Annular choroidal detachment in a patient with Vogt-Koyanagi-Harada disease.
AB  - BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is one of the diseases that show
      choroidal detachment. However, there are few reports about VKH disease associated
      with annular choroidal detachment. In this study, we describe an unusual case of
      VKH disease with an annular choroidal detachment and absence of a serous retinal
      detachment. METHODS: The study was an interventional case report. A 59-year-old
      Japanese woman presented with bilateral blurred vision with meningismus.
      Laboratory and clinical investigations were performed, including fluorescein
      angiography, B-scan echography, computed tomography scans, magnetic resonance
      imaging, cerebrospinal fluid examination, and blood examination including HLA
      typing. After a diagnosis of VKH disease was made, the patient was treated with
      systemic corticosteroids. RESULTS: The patient had iridocyclitis, optic disc
      swelling, choroidal thickening, and annular choroidal detachment in both eyes.
      Ophthalmoscopic examination did not reveal an obvious serous retinal detachment.
      Fluorescein angiography showed prominent leakage of dye from the optic disc and
      mild dye pooling in the subretinal space. The sclera was not thickened, and the
      axial lengths were relatively short. The findings were bilateral and symmetrical.
      Cerebrospinal fluid pleocytosis and HLA typing were consistent with VKH disease.
      After systemic corticosteroid treatment, the abnormal findings were resolved.
      Neither sunset glow fundus nor cutaneous lesions were observed, and no
      recurrences were observed during 4 years of follow-up. CONCLUSION: The annular
      choroidal detachment was probably caused by severe choroidal inflammation and
      resistance to scleral outflow because of the scleral abnormality due to
      inflammation and short axial length. We believe that intact and functioning
      retinal pigment epithelium prevented serous retinal detachment. This case reports
      annular choroidal detachment without retinal detachment associated with VKH
      diseases.

PMID- 14963716
TI  - Ocular symptoms and signs in patients with ectodermal dysplasia syndromes.
AB  - PURPOSE: The ectodermal dysplasia syndromes are underestimated although precise
      inclusion criteria have been formulated. The purpose is to establish easily
      detectable ophthalmologic symptoms and signs as reliable criteria for ectodermal
      dysplasia syndromes. METHODS: Thirty-six patients with confirmed ectodermal
      dysplasia syndromes were included in an observational case series: hypohidrotic
      ectodermal dysplasia (30), EEC syndrome (3), AEC syndrome (2), Gorlin-Goltz
      syndrome (1). Each patient was examined ophthalmologically. The principal outcome
      measures were ocular symptoms and signs in patients with different ectodermal
      dysplasia syndromes of varying severity. METHODS: Some 94.4% of the patients
      suffered from dry eye symptoms. Reduction of eyebrows was seen in 94.4%; the
      lashes were altered in 91.6%. Changes of the meibomian glands were detected in
      95.45%. Corneal changes such as pannus occurred later in life. CONCLUSIONS:
      Alterations of the meibomian glands, which were detected by meibomianoscopy, are
      the most reliable ocular sign of ectodermal dysplasia syndromes.

PMID- 14963717
TI  - Characterization of the basic fibroblast growth factor-evoked proliferation of
      the human Muller cell line, MIO-M1.
AB  - BACKGROUND: Basic fibroblast growth factor (bFGF) has been suggested to mediate
      activation of Muller glial cells in the ischemic-hypoxic retina. However, the
      intracellular pathways activated by bFGF in human Muller cells have been little
      explored. We characterized the signaling transduction pathways which are involved
      in the control and growth factor-evoked proliferation of a recently described
      human Muller cell line, MIO-M1. In addition, we investigated whether bFGF evoked
      the release of vascular endothelial growth factor (VEGF) and hepatocyte growth
      factor (HGF) from the cells. METHODS: The growth factor-evoked proliferation of
      cultured MIO-M1 cells was estimated by means of a bromodeoxyuridine immunoassay,
      in the absence and presence of blockers of mitogen-activated protein kinases
      (MAPKs) and of the phosphatidylinositol-3 kinase (PI3K). The activation state of
      the p44/p42 MAPK was determined by Western blotting, and the bFGF-evoked release
      of VEGF and HGF was evaluated by ELISA. RESULTS: bFGF evoked a concentration
      dependent increase of the cell proliferation, with an EC50 of approximately 1
      ng/ml, via activation of both the p44/p42 MAPK and the p38 MAPK. In contrast, the
      mitogenic effects of the platelet-derived and the heparin-binding epidermal
      growth factors were dependent on p44/p42 MAPK activation and independent of
      activation of p38 MAPK. The transforming growth factors beta1 and beta2 also
      evoked cell proliferation which was independent of activation of the MAPKs
      investigated. bFGF evoked a release of VEGF and of HGF by the cells; these
      effects were independent of MAPK activation and were possibly mediated by
      activation of the PI3K signaling pathway. CONCLUSION: bFGF evokes multiple
      intracellular signaling pathways in human Muller cells which underlie the gliotic
      cell responses upon ischemic-hypoxic insults in the retina. Beside the
      stimulation of cell proliferation, which is dependent on activation of p44/p42
      and p38 MAPKs, bFGF induces the secretion of VEGF and HGF by Muller cells.

PMID- 14963718
TI  - A parent-of-origin detectable polymorphism in the hypermethylated region upstream
      of the human H19 gene.
AB  - The H19 gene is a paternally imprinted gene located on chromosome 11p15.5. In
      this study the H19FR haplotype polymorphism including three SNPs upstream of the
      H19 gene was investigated. Six genotypes derived from three alleles were detected
      in the Japanese population by means of PCR and subsequent constant denaturing gel
      electrophoresis. Based on the methylation status of the genomic DNA from blood
      samples, selective detection of the parental allele for H19FR was examined by
      using two types of enzyme, the methylation-sensitive restriction enzymes HpaII or
      HhaI and McrBC. Genomic DNA digested by either HpaII or HhaI, revealed a single
      band derived from the paternal allele, as a result of cleavage of unmethylated
      recognition sites on the maternal allele. On the contrary, the use of McrBC,
      which can digest a methylated paternal sequence, resulted in exclusively
      amplifying the maternal allele. This method could be one of the useful techniques
      for discriminating the parental origin of alleles.

PMID- 14963719
TI  - Cytokine profile in paranasal effusions in patients with chronic sinusitis using
      the YAMIK sinus catheter with and without betamethasone.
AB  - Recently, the YAMIK sinus catheter (YAMIK) has been reported to be a useful
      therapeutic device in the treatment of sinusitis. The present study was conducted
      to compare its delivery of either a normal saline (NS) or a betamethasone
      solution (0.4 mg/ml) into the paranasal sinuses of 25 patients (39 sides) with
      chronic sinusitis. The following parameters were evaluated: (1) subjective nasal
      clinical symptoms (nasal discharge, nasal obstruction, postnasal drip and
      headache), (2) X-ray photographs (ethmoid and maxillary sinuses) and (3) cytokine
      levels (IL-1beta, IL-8 and TNF-alpha) by enzyme-linked immunosorbent assay. The
      total nasal symptom scores significantly decreased after the first therapy, and
      the total X-ray photograph scores significantly decreased after therapy with
      either NS or the betamethasone solution. In both NS and betamethasone patients,
      the levels of IL-1beta and IL-8 had significantly decreased by the 3rd and 2nd
      weeks after therapy, respectively. In contrast, the TNF-alpha level decreased
      after the first therapy with betamethasone solution and remained unchanged after
      therapy with NS. These findings suggest that evacuation of the pathological
      effusions in sinuses may exert a beneficial effect by reducing the levels of IL
      1beta and IL-8, and we speculate that removal of pathological effusions from the
      sinuses may provide treatment through different mechanisms than those that occur
      in treatment with betamethasone.

PMID- 14963720
TI  - An unusual foreign body in the oesophagus. The body packer syndrome.
AB  - We report a case of drug smuggling by internal concealment of heroin in the
      oesophagus. We review the literature and discuss presentation and management
      highlighting the need to maintain an awareness of "body packer syndrome" in the
      differential diagnosis of ingested foreign bodies.

PMID- 14963721
TI  - The distribution of free calcium ions in the cholesteatoma epithelium.
AB  - The distribution of free calcium ions in normal skin and cholesteatoma epithelium
      was investigated using the oxalate precipitation method. In agreement with
      previous observations, we could demonstrate a calcium ion gradient in normal
      epidermis where the cells in stratum basale and spinosum reside in an environment
      containing relatively low concentrations of calcium ions, whereas the outer
      stratum granulosum contained abundant calcium. The concentration declined
      precipitously in the stratum corneum. In contrast, in cholesteatomas, the
      gradient was perturbed in some areas of the nucleated layers and areas appeared
      where oblong accumulations of free calcium ions were found basally in the
      stratum. These findings provide evidence that fluctuations in epidermal calcium
      in cholesteatoma epithelium may underlie the abnormal desquamation, may
      contribute to the formation of an abnormal permeability barrier and may regulate
      terminal events in epidermal differentiation.

PMID- 14963722
TI  - Malassezia furfur induces the expression of beta-defensin-2 in human
      keratinocytes in a protein kinase C-dependent manner.
AB  - Antimicrobial peptides of the beta-defensin family are expressed in all human
      epithelial tissues tested to date and have recently been the subject of vigorous
      investigation. Their localization and characteristics support the hypothesis that
      these peptides play a role in mucosal and skin defense. The lipophilic yeast
      Malassezia furfur is a saprophyte found in normal human cutaneous flora.
      Malassezia furfur is not only a saprophyte, but is also associated with several
      diseases such as Malassezia folliculitis, seborrheic dermatitis and some forms of
      atopic dermatitis, psoriasis and confluent and reticulate papillomatosis. Little
      is known about the mechanism by which M. furfur overcomes the natural barrier of
      the skin. To further define the role of the beta-defensins in the innate human
      skin immune response, we analyzed the mRNA expression of two human beta-defensins
      HBD-1 and HBD-2 in human keratinocytes treated with M. furfur. In addition, we
      looked into how M. furfur of TGF-beta1 and IL-10, cytokines that interfere with
      the development of protective cell immunity, regulate their expression. Finally,
      we examined the signal transduction mechanisms involved during M. furfur uptake.
      Cultured human keratinocytes were treated with M. furfur. The mRNA and protein
      expression were analyzed, respectively, by reverse transcriptase polymerase chain
      reaction (RT-PCR) and Western blotting. Our data demonstrate that M. furfur does
      not modify HBD-1 expression, whereas it up-regulates, via protein kinase C (PKC),
      the expression of HBD-2, TGFbeta-1 and IL-10 48 h after treatment. Our results
      suggest that beta-defensins are integral components of innate host defenses. They
      play an essential part in the resistance of the human skin surfaces against M.
      furfur uptake and other microbial invasion.

PMID- 14963723
TI  - The effect of meniscus compression on the biomechanical properties of repaired
      meniscal lesions. Winner of the AGA-DonJoy Award 2003.
AB  - INTRODUCTION: The objective of the present study was to investigate the influence
      of meniscus compression, as it occurs with weight-bearing, on the biomechanical
      behavior of different repair types. MATERIALS AND METHODS: Young human meniscal
      tissue specimens were fitted with a single Bionx Arrow, a Innovasive Meniscal
      Screw, or a vertical suture (Ethibond 2-0) according to standard clinical
      practice. Test specimens then underwent repetitive loading with 10 N under 1 N
      pretension up to a maximum of 1182 cycles and were finally loaded to failure.
      Half of the cases in each group were additionally subjected to synchronized
      intermittent compression during the test. The main variables investigated were
      the number of cycles survived and ultimate failure load. To reduce the
      complexity, investigations were limited to the peripheral repair site. RESULTS:
      The number of cycles survived was significantly affected by compression and the
      type of repair. Arrows and Screws survived 311 and 52 cycles, respectively,
      without compression, while 983 and 1182 cycles were survived with added
      compression. In the suture group, no premature failure occurred either with or
      without compression. Both compression and the type of repair had a significant
      effect on the ultimate failure load. It increased about twofold in the Arrow and
      Screw group, while the suture group was not affected. CONCLUSIONS: Compression of
      the meniscus can substantially increase the pullout resistance of meniscal repair
      implants and thus seems not to be a factor negatively influencing the stability
      of the repair.

PMID- 14963724
TI  - The beneficial effect of mild hypothermia in a rat model of repeated
      thromboembolic insults.
AB  - The post-thrombotic brain has recently been reported to have an enhanced
      vulnerability to a second embolic insult. Although postischemic hypothermia is
      neuroprotective in global and focal ischemia models, the effect of mild
      hypothermia on outcome after thromboembolic insults has not been evaluated. This
      study therefore determined whether brain hypothermia (33 degrees C) was
      neuroprotective against repeated thromboembolic insults. Photochemically induced
      non-occlusive common carotid artery thrombosis (CCAT) leading to platelet
      embolization to the brain was induced in anesthetized rats ( n=35). Thirty
      minutes after CCAT, brain temperature was maintained at normothermic (37 degrees
      C) or hypothermic (33 degrees C) levels for 4 h followed by a slow rewarming
      period (1.5 h). Three days later, rats underwent a secondary CCAT insult under
      normothermic conditions and were allowed to survive for an additional 3 days
      prior to perfusion fixation and quantitative histopathological assessment.
      Compared to normothermic animals, mild hypothermia after the first embolic insult
      produced a significant reduction ( P>0.05) in overall infarct volume. Hypothermia
      reduced total infarct volume from 7.55+/-2.32 mm(3) (mean +/- SEM) in
      normothermic rats to 2.56+/-0.88 mm(3) in hypothermic animals undergoing repeated
      insults. Histopathological analysis also demonstrated less evidence for focal
      hemorrhage in the cooled groups. These data demonstrate that mild hypothermia is
      protective in a thromboembolic stroke model. In addition, post-thrombotic
      hypothermia decreases the histopathological vulnerability of the post-thrombotic
      brain to secondary embolic insults. These findings may be important in the
      prevention of stroke in patients at risk.

PMID- 14963725
TI  - Localisation of a carbohydrate epitope recognised by human IgE in pollen of
      Cupressaceae.
AB  - The objectives of the present study were: (1) to localise, at the subcellular
      level, the allergens in pollen of Cupressaceae species, using a monoclonal
      antibody (mAb 5E6) that is specific for carbohydrate epitopes of allergenic
      components of Cupressus arizonica pollen extract; (2) to determine whether the
      glycidic epitope recognised by mAb 5E6 was present in pollen of allergenic
      species taxonomically unrelated to Cupressaceae; and (3) to determine whether
      human IgE purified from monosensitive patients recognises the same epitope as mAb
      5E6 in Cupressaceae pollen. Immunogold labelling of mAb 5E6 showed a high density
      of gold particles on the orbicules, supporting the hypothesis that they are
      important vectors of allergens. A high density was also found on the exine and in
      the cytoplasm, with the latter finding confirming that fragments of pollen
      ruptured under humid conditions can represent a vector. The glycidic epitope
      recognised by mAb 5E6 was detected in all of the species taxonomically unrelated
      to Cupressaceae, although with varying density. Human IgE recognised the same
      epitope as mAb 5E6. These findings are consistent with observations of diffuse
      allergenic cross-reactivity among various allergens. The in situ localisation of
      a common epitope recognised by both a monoclonal antibody and human IgE could be
      of importance in immunotherapy.

PMID- 14963726
TI  - Evaluation of a skin reference electrode used for intraoral pH measurements in
      combination with a microtouch electrode.
AB  - The aim of this in vivo study was to evaluate a skin reference electrode used
      with the microtouch method for measurements of intraoral pH. Registrations of
      plaque pH were made in ten healthy subjects before and up to 30 min after a mouth
      rinse with 10% sucrose. A microtouch electrode (Beetrode) was used in combination
      with two different half-cell reference electrodes: a skin silver-silver chloride
      plate or a glass capillary reference electrode. The skin electrode was placed on
      the subject's forearm in combination with a conductive gel. The glass capillary
      electrode, together with one of the test subject's fingers, was placed in a
      beaker with a 3 M KCl solution. High agreement between the two reference systems
      resulted in almost identical plaque-pH curves (r=0.97). The mean differences
      between the two systems at the different time points varied between -0.15 and
      +0.01 pH units, with an overall mean pH difference of 0.03 pH units. It can be
      concluded that the use of the skin reference electrode may very well replace the
      traditional reference electrode used in combination with a microtouch electrode
      for intraoral use.

PMID- 14963727
TI  - Antenatal screening and early intervention for "perinatal" distress, depression
      and anxiety: where to from here?
AB  - Recent developments in the study of mental health issues surrounding childbirth,
      have brought about a shift from the narrow concept of "postnatal depression"
      (PND) to a consideration of the spectrum of depressive and anxiety disorders
      arising in the "perinatal" period - which in the mental health context is defined
      as encompassing pregnancy and the first year postpartum. This shift has been
      associated with a growing recognition of the potential for prevention and early
      intervention in the perinatal period. In this article, the difficulties of
      antenatal screening with the aim of predicting PND are highlighted and contrasted
      with the potential benefits of antenatal screening aimed at identifying
      psychological morbidity - whether pre-existing risk factors and/or current
      symptoms - which may have bearing across the entire perinatal period. The
      literature on randomized controlled trials of "targeted" antenatal interventions
      to reduce PND and "indicated" interventions in postnatally depressed women are
      also reviewed. Future clinical and research directions in the field of early
      intervention for perinatal mood and anxiety disorders are identified.

PMID- 14963728
TI  - Grief and its impact on prenatal attachment in the subsequent pregnancy.
AB  - This article suggests there is a need to reframe the phenomenon of unresolved
      grief in parents who are in a subsequent pregnancy after a previous loss using a
      prenatal attachment model. An argument is made for helping parents give meaning
      to their parenting role for the baby who has died so they can move forward in
      attaching to the baby in the next pregnancy. It is suggested that a new layer of
      grief surfaces when parents get pregnant again which can lead to pathology if not
      recognized by others. Interventions to support the parenting relationship to the
      baby in the subsequent pregnancy are provided.

PMID- 14963729
TI  - Stressful life events, personal losses, and perimenopause-related depression.
AB  - We compared the number and quality of life events reported by depressed
      perimenopausal women and a non-depressed comparison group. Additionally, we
      examined the effects of the presence of hot flushes on life event reports. All
      women were 44-55 years old, had irregular menses and elevated plasma gonadotropin
      levels. The Psychiatric Epidemiology Research Interview recorded both the
      frequency of occurrence and the desirability of life events experienced by the
      women during the six months prior to the interview. Depressed perimenopausal
      women (n=50) reported significantly more undesirable events [Student's t-test
      (unpaired) with Bonferroni correction, t(98)=3.9, p=0.001] but not more exit
      events (e.g., divorce, last child leaving home or death in family) (t(98)=0.9,
      p=NS) compared to the non-depressed women (n=50). There were no effects of hot
      flushes on these diagnostic differences. The "empty nest" syndrome does not
      appear to be relevant in the development of perimenopausal depression.
      Nevertheless, independent of the presence of hot flushes, perimenopausal
      depressed women are more likely to report both negative life events and
      diminished self esteem.

PMID- 14963730
TI  - Neuropsychological profile of Alzheimer's disease in women: moderate and
      moderately severe cognitive decline.
AB  - INTRODUCTION: Alzheimer's disease (AD) is characterised by progressive cognitive
      and functional decline. There is evidence that AD is more prevalent in women.
      This study aims at identifying the clinical and sociodemographic variables
      associated with the cognitive functions and the pattern of decline in women with
      moderate to moderately severe AD. METHODS: Cross-sectional observational study of
      165 women with dementia of the AD type according to NINCDS-ADRDA criteria. The
      cognitive functions were assessed using the Cambridge Cognitive Examination
      (CAMCOG). The sociodemographic and clinical data were collected from the
      Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) interview, and
      the Neuropsychiatric Inventory (NPI) was administrated to the caregiver. RESULTS:
      The number of years of schooling and the score on the CAMDEX depression scale
      were the variables associated with the CAMCOG score. The effect of these
      variables was not homogenous for all the CAMCOG subtests. CONCLUSIONS: The number
      of years of schooling and the presence of depressive symptomatology influence the
      results of the neuropsychological exploration, but the effect is moderate and not
      homogenous for all the CAMCOG subtests. The differences in cognitive profile
      between moderate and moderately severe are characterised by a greater effect on
      temporal orientation, calculation and perception.

PMID- 14963731
TI  - Premenstrual dysphoric disorder and psychiatric co-morbidity.
AB  - Premenstrual dysphoric disorder (PMDD) can occur co-morbidly with other axis I
      disorders, particularly mood and anxiety disorders. The data supporting this
      diagnostic dilemma are reviewed in terms of methodological comparisons between
      studies. The point prevalence of the co-occurrence of PMDD and other psychiatric
      disorders is discussed as well as implications for treatment and further study.

PMID- 14963732
TI  - Mother-baby inpatient psychiatric care in different countries: data collection
      and issues - introduction.
AB  - The material was presented during a symposium on "Mother-Baby joint admission for
      mental health care in different countries" at the Marce Society International
      Biennial Scientific Meeting in Sydney (Australia) in 2002 (25-27 September 2002).
      The introduction stresses the main contribution of each of the six papers. It
      discusses the general context of perinatal psychiatry and offers guidelines for
      perinatal health care.

PMID- 14963733
TI  - The history of Mother-Baby Units (MBUs) in France and Belgium and of the French
      version of the Marce checklist.
AB  - Until fairly recently, mentally ill mothers were separated from their new-borns
      because of the potential danger to the baby. Over the past 50 years, however, we
      have learned more about the perinatal period, with the development of child
      psychiatry and interest in maternal postpartum disorders. This knowledge has led
      psychiatric departments to develop new ways to provide care without separating
      mentally ill mothers from their babies. Joint full-time admissions began in Great
      Britain in 1948. The first Mother-Baby Unit (MBU) in France opened in 1979 and in
      Belgium in 1990. In 2003, there are 17 MBUs in France and 3 in Belgium. From 1995
      to 1998, Odile Cazas and Nine Glangeaud, working with a group of child and adult
      psychiatrists and psychologists, adapted the English Marce Checklist to the
      French and Belgian health and child protective systems and added items useful for
      research.

PMID- 14963734
TI  - Mother-Baby psychiatric units (MBUs): national data collection in France and in
      Belgium (1999-2000).
AB  - The French version of the Marce checklist was used to collect data for 176 joint
      admissions to 11 psychiatric mother-baby units in 1999 and 2000. Mean age of the
      babies at admission ranged from 4 to 16 weeks. Two units also admitted older
      children. Mothers admitted were diagnosed with schizophrenia or chronic
      delusional disorders (n = 44), acute transitory psychosis "Bouffee delirante" (n
      = 20), bipolar disorders (n = 20), depressive illness (n = 38), personality
      disorders or intellectual disability (n = 39), and other disorders (n = 15). The
      mean duration of hospitalisation was 11 weeks. Units that also offered day-care
      admission in the same or a near-by unit had shorter mean admissions. More than
      half the women's partners (or babies' fathers) had mental health problems. Women
      with schizophrenia or chronic delusional disorders and personality disorders or
      intellectual disability remained hospitalised longer, improved less, and were
      more often separated from their babies, or discharged with supervision, than
      women admitted with other diagnoses.

PMID- 14963735
TI  - A national audit of joint mother and baby admissions to UK psychiatric hospitals:
      an overview of findings.
AB  - The Marce Clinical Audit is an ongoing data collection exercise that gathers
      socio-demographic and clinical information about mothers and their infants,
      admitted jointly to specialist units in UK psychiatric hospitals. The maternal
      and parenting outcomes, in particular of mothers with schizophrenia and mothers
      who harm themselves and/or their infants, were determined and analysed. The
      majority of women had a primary diagnosis of either depression (43%) or
      schizophrenia (21%). Mothers with schizophrenia were three times more likely to
      experience a poor outcome than non-schizophrenic mothers, were more likely to be
      separated from their infant at discharge and were perceived, by staff, to be at
      greater risk of harming their infant. They were, however, shown to be no more
      likely to cause actual harm to their infant, or themselves, than non
      schizophrenic mothers.

PMID- 14963736
TI  - A perinatal psychiatric service audit in New Zealand: patient characteristics and
      outcomes.
AB  - As part of a clinical audit, data were collected on all patients assessed and
      offered treatment by the Christchurch 'Mothers and Babies' Service between 1-7-98
      and 30-6-2000. At assessment and discharge a comprehensive psychiatric interview
      and the Marce Checklist were completed by clinicians and self-rating
      questionnaires were completed by the patient. Univariate analysis and logistic
      regression were performed on the variables collected. A significant proportion of
      women suffered from chronic recurrent psychiatric disorders. Pure 'postnatal
      depression' was uncommon. Thirty-eight percent of women were pregnant at
      assessment. Risk factors for poor maternal outcomes included history of chronic
      illness, high symptomatic scores at assessment, the presence of more than one
      Axis I diagnosis (excluding nicotine dependence) or an Axis II diagnosis, and
      poor interpersonal relationships. Perinatal psychiatric services need resources
      to treat women with a range of severe and chronic disorders and should pay
      attention to interpersonal issues in treatment.

PMID- 14963737
TI  - Mother-baby psychiatric units in Australia - the Victorian experience.
AB  - This article reviews the women admitted to Mother Baby Psychiatric Units in 2002,
      in the State of Victoria, Australia, looking at characteristics of postpartum
      disorders with respect to admission and outcome in a region with a high number of
      mother-baby unit beds relative to other Australian regions and other cities.
      Differences among units are noted, including the differential impact of whether
      the unit is associated with a psychiatric service or an obstetric service. This
      includes length of stay and referral patterns. Details of diagnosis, admission
      and outcome are compared to similar admissions in the United Kingdom, with
      similar factors predictive of poor outcome, defined as separation from the
      infant. Mother-Baby Units have an important potential role in improving these
      outcomes, with longer-term studies of these women needed.

PMID- 14963738
TI  - Treatment of maternal mood disorder and infant behaviour disturbance in an
      Australian private mothercraft unit: a follow-up study.
AB  - Australia has a system of residential parentcraft services which offer brief
      admissions to mothers experiencing difficulties with infant care and postnatal
      mood disturbance. Most of these are state-funded public access services. In 1996
      a comparable but differentiated service was opened in the private sector. Masada
      Private Hospital Mother Baby Unit accommodates five mother-infant pairs who are
      admitted to a five-night structured residential program. Care is provided by a
      multidisciplinary team comprising a paediatrician, general practitioner, clinical
      psychologist and specialist nurses. Complex maternal mood disorders as measured
      on standardised psychometric instruments include depression, anxiety and severe
      occupational fatigue. Their babies are unsettled, cry for prolonged periods, wake
      frequently at night and do not sleep well during the day. Many have feeding
      difficulties. The treatment program comprises both individualised training in
      infant care and settling strategies and psycho-educational groups offered in a
      supportive non-judgemental setting. One month post-discharge maternal mood is
      significantly improved and infant behaviour more manageable compared with
      functioning on admission.

PMID- 14963741
TI  - Clinical outcome of standard extracranial-intracranial bypass surgery in patients
      with symptomatic atherosclerotic occlusion of the internal carotid artery.
AB  - OBJECTIVE: In this retrospective study we wanted to determine the role of
      cerebral revascularization in patients with symptomatic occlusive cerebrovascular
      disease. Special emphasis was put on subsequent cerebrovascular events, benefit
      in neurological functioning and bypass patency, as evaluated during the follow-up
      period. METHODS: A total of 73 superficial temporal artery to the middle cerebral
      artery bypasses were performed on 67 patients from 1986-2000. All patients
      exhibited a symptomatic occlusion of the internal carotid artery verified by
      angiography. All patients in our group were refractory to medical treatment. 65
      patients (69 bypasses) with a mean age of 61 years (range: 38-79 years) were
      followed up over an average time of 44 months (range: 1.5-150 months). RESULTS:
      The peri-operative morbidity rate was 3% with no mortality. 55 patients (85%) had
      no further cerebrovascular events after surgery, and only 7 (11%) patients
      experienced another cerebrovascular event. 57 (88%) patients showed an
      improvement of symptoms after surgery and only 1 patient fared worse during the
      follow-up period due to a stroke he suffered two years after bypass surgery. 90%
      of all bypasses remained patent during the follow-up. CONCLUSIONS: Although
      bypass surgery for occlusive cerebrovascular disease is still controversial, our
      retrospective study suggests both an improvement of symptoms and signs and a risk
      reduction for future cerebrovascular events after surgery.

PMID- 14963742
TI  - Non-operative treatment of spontaneous spinal epidural hematomas: a review of the
      literature and a comparison with operative cases.
AB  - OBJECTIVE: To identify factors that favour spontaneous recovery in patients who
      suffered a spontaneous spinal epidural hematoma (SSEH). METHODS: The literature
      was reviewed regarding non-operative cases of SSEH (SSEH(cons)). Sixty-two cases
      from the literature and 2 of our own cases were collected, focusing on sex, age,
      medical history, position of the hematoma, segmental distribution and length of
      the hematoma, diagnostic imaging, neurological condition and outcome. Those data
      were analysed and compared with the data from a literature review of 474 cases
      operated on because of a SSEH (SSEH(oper)). RESULTS: The mean length of the
      hematoma was significantly higher in SSEH(cons), compared to SSEH(oper) (5.4
      versus 4.2 vertebral segments; [standard error of the difference (SED) is 0.38
      vertebral segments; 95% confidence limits for the difference are 0.45 to 1.95]).
      Also after exclusion of patients with coagulopathy, mean length of the hematoma
      was significantly higher in SSEH(cons) (4.7 versus 3.9 vertebral segments [SED is
      0.39 vertebral segment; 95% confidence limits for the difference are 0.04 to
      1.56]). Neurological signs and symptoms in SSEH(cons) were significantly less
      severe (P<0.005) and diagnosis was based on Magnetic Resonance Imaging (MRI) in
      the majority of cases (P<0.0005), when compared to SSEH(oper). All other patient
      characteristics showed no correlation with spontaneous recovery. CONCLUSION: The
      recent increase of publications of SSEH(cons) has to be explained by the
      introduction of MRI in daily medical practice. As a result, more patients with a
      mild or benign clinical course are being diagnosed. In earlier times those
      patients would have escaped medical attention. The mean length of the hematoma in
      SSEH(cons) appears to be significantly higher compared to SSEH(oper). This
      suggests that spontaneous regression of neurological symptoms may result from
      decompression of the neural structures by spreading of the (liquid) hematoma
      along the spinal epidural space in the early stages after haemorrhage. Based on
      the present review, there appear to be no factors which promote conservative
      treatment in SSEH. In the majority of cases with SSEH, the mainstay of treatment
      will remain surgical decompression of the neural structures and removal of the
      hematoma. The decision for conservative treatment has to be based on the severity
      of the neurological deficit and on the clinical course. Retrospectively, the
      length of the hematoma seems to give a clue to the spontaneous recovery which
      occurs in some cases of SSEH. Nevertheless, hematoma-length can not be used as a
      guide to treatment.

PMID- 14963743
TI  - Plasminogen activation in neurofibromatosis 2-associated and sporadic
      schwannomas.
AB  - BACKGROUND: Schwannomas are usually benign tumours which occur sporadically or in
      association with neurofibromatosis 2 (NF2), an autosomal dominant disorder.
      Invasiveness and higher proliferative potential compared to sporadic tumours are
      features of NF2-associated schwannomas. METHOD: We studied urokinase (uPA),
      tissue-type plasminogen activator (tPA), urokinase receptor (uPAR) and
      plasminogen activator inhibitor-1 (PAI-1) expression by in situ hybridization and
      by immunohistochemistry in 14 NF2 and 15 sporadic patients with 34 schwannomas.
      uPAR and vitronectin immunohistochemistry were also studied. Three sural nerve
      specimens were included as Schwann cell controls. FINDINGS: Both schwannoma
      groups expressed prominent levels of uPA and tPA. Semiquantitative analysis of
      the in situ hybridization and immunoreactivity demonstrated that NF2 schwannomas
      expressed less PAI-1 at the mRNA level than sporadic schwannomas (score 1.63+/
      0.41 vs. 2.05+/-0.75) and less total PAI-1 at the antigen level (score 1.55+/
      0.66 vs. 2.07+/-0.56). PAI-1 was mostly in a free form in NF2 schwannomas
      compared to the sporadic counterparts (score 1.85+/-0.73 vs. 1.46+/-0.58),
      whereas there was less uPAR antigen in NF2 schwannomas than in the sporadic
      counterparts (score 1.18+/-0.49 vs. 1.68+/-0.56). Sural nerve Schwann cells did
      not express detectable level of PAI-1 and at the most a minor amount of tPA.
      CONCLUSIONS: Schwann cells of tumour cell origin, both in sporadic and NF2
      schwannomas, expressed elevated levels of plasminogen activators and PAI-1
      compared to normal suralic nerve Schwann cells. Furthermore, there seemed to be
      an imbalance in the PA-PAI-1 system in NF2-associated schwannomas. Although our
      methods are more descriptive than quantitative, we suggest that the somewhat more
      aggressive behavior of NF2-associated schwannomas compared to sporadic
      schwannomas may be based on the local proteolytic activity.

PMID- 14963744
TI  - Chiari I malformation related syringomyelia: radionuclide cisternography as a
      predictor of outcome.
AB  - BACKGROUND: This prospective study, conducted in patients with Chiari I
      malformation (C I) related syringomyelia who underwent posterior decompression
      and duroplasty, utilizes radionuclide cisternography in order to study the
      cerebrospinal fluid (CSF) dynamics at the foramen magnum and to predict the
      clinical outcome following surgery. METHODS: 17 consecutive patients of C I with
      syringomyelia (but without hydrocephalus or fixed atlanto-axial dislocation),
      underwent a detailed neurological examination and were assigned a clinical
      disability score based on the modified Klekamp and Samii score. A radionuclide
      cisternography (using Tc99m-DTPA) was performed via the lumbar route and the
      ascent of the tracer was followed utilizing a gamma camera immediately after
      injection and then sequentially after 1, 2, 4, 6 and 24 hours. After posterior
      decompression and duroplasty, the modified Klekamp and Samii score was repeated
      at follow-up visits (range: 3 months to one year) along with radionuclide
      cisternography at 3 months, and MR imaging at 6 months. FINDINGS: Three patterns
      of tracer flow were observed: a). rapid flow (n=7); b). supratentorial
      subarachnoid delay (n=7); and, c). foramen magnum block (n=3). The patients
      having foramen magnum block had the poorest clinical scores on admission. At
      follow up, there was an improvement in the clinical scores so that the mean
      scores in all three categories reached nearly the same level. Following posterior
      decompression, the radionuclide cisternography performed in 10 patients showed a
      rapid flow of the tracer without any obstruction. The syrinx resolved in 4 of the
      11 patients in whom an MRI was done. INTERPRETATION: The patients with C I with
      syringomyelia may often have a free flow of tracer across the FM. Posterior
      decompression and duroplasty provides maximum clinical relief in patients with a
      demonstrable foramen magnum block on radionuclide cisternography while those with
      a normal flow have less relief. The symptomatology related to brain-stem
      compression immediately responds to the surgical procedure but the syrinx-induced
      signs and symptoms of spinal cord dysfunction persist.

PMID- 14963745
TI  - Intracranial hypertension: what additional information can be derived from ICP
      waveform after head injury?
AB  - OBJECTIVE: Although intracranial hypertension is one of the important prognostic
      factors after head injury, increased intracranial pressure (ICP) may also be
      observed in patients with favourable outcome. We have studied whether the value
      of ICP monitoring can be augmented by indices describing cerebrovascular pressure
      reactivity and pressure-volume compensatory reserve derived from ICP and arterial
      blood pressure (ABP) waveforms. METHOD: 96 patients with intracranial
      hypertension were studied retrospectively: 57 with fatal outcome and 39 with
      favourable outcome. ABP and ICP waveforms were recorded. Indices of
      cerebrovascular reactivity (PRx) and cerebrospinal compensatory reserve (RAP)
      were calculated as moving correlation coefficients between slow waves of ABP and
      ICP, and between slow waves of ICP pulse amplitude and mean ICP, respectively.
      The magnitude of 'slow waves' was derived using ICP low-pass spectral filtration.
      RESULTS: The most significant difference was found in the magnitude of slow waves
      that was persistently higher in patients with a favourable outcome (p<0.00004).
      In patients who died ICP was significantly higher (p<0.0001) and cerebrovascular
      pressure-reactivity (described by PRx) was compromised (p<0.024). In the same
      patients, pressure-volume compensatory reserve showed a gradual deterioration
      over time with a sudden drop of RAP when ICP started to rise, suggesting an
      overlapping disruption of the vasomotor response. CONCLUSION: Indices derived
      from ICP waveform analysis can be helpful for the interpretation of progressive
      intracranial hypertension in patients after brain trauma.

PMID- 14963746
TI  - Hippocampal microdialysis during spontaneous intraoperative epileptiform
      activity.
AB  - BACKGROUND: The actual mechanisms underlying human hippocampal epileptogenicity,
      a process ultimately mediated by neurochemical events, remains to be fully
      elucidated. We submit early insight data regarding microdialysis (MD) recovery of
      the neuroactive amino acids glutamate, aspartate and gamma-aminobutyric acid
      (GABA) from the intraoperative and intact, spontaneously epileptiform human
      hippocampus. METHOD: Generally anaesthetised temporal lobe epilepsy (TLE)
      patients (N=7) undergoing therapeutic and anatomically standardised resective
      surgery were also subjected to ipsilateral anterior hippocampal MD with
      concomitant hippocampal electrocorticography (ECoG). Recovered 10-min dialysate
      samples were quantified for glutamate, aspartate and GABA using high-performance
      liquid chromatography; corresponding ECoG data was assessed for epileptiform
      activity (EA); mesial resection tissue was postoperatively examined and graded
      for hippocampal sclerosis. FINDINGS: Mean 'Sample 3' dialysate absolute recovery
      of glutamate, aspartate and GABA from hippocampi with minimal EA (N=5) was (
      micro M+/-SEM): 6.406+/-2.143, 0.600+/-0.215, and 0.357+/-0.093, respectively. In
      contrast, 'Sample 3' dialysate absolute glutamate, aspartate and GABA levels (
      micro M) from the hippocampi of two patients with vigorous EA were: 101.099 and
      211.861, 21.860 and 14.482, and 4.241 and 4.817, respectively. Mesial resection
      tissue in all cases demonstrated hippocampal sclerosis, though the
      histopathological degree of sclerosis varied between patients. INTERPRETATION:
      These preliminary intraoperative findings suggest that dialysate glutamate,
      aspartate, and GABA levels from the sclerotic anterior hippocampus likely
      reflects the functional status of the sampled tissue - i.e., lower levels of
      these neuroactive amino acids are to be expected during quiescent or minimal EA
      versus considerably higher levels corresponding to vigorous EA.

PMID- 14963747
TI  - The origin of brain metastases in patients with an undiagnosed primary tumour.
AB  - BACKGROUND: In patients presenting brain metastases as the first manifestation of
      a previously undiagnosed primary tumour (UDP) histopathological confirmation of
      the diagnosis can be obtained by either direct surgical sampling of the brain
      lesion or paraclinical search for an accessible primary tumour. The sequence of
      the diagnostic work-up and the timing of an eventual neurosurgical intervention
      are a matter of debate and are mainly influenced by the distribution of primary
      tumours in UDP patients. The aim of this study was to verify the hypothesis that
      the distribution of primary tumours differs between UDP patients and the rest of
      the patients with brain metastases (DP), and to propose a diagnostic work-up
      specifically tailored to the UDP population. METHODS: Retrospective study on 342
      patients admitted to the Lausanne University hospital between 1983 and 1998 with
      the diagnosis of cerebral metastases. FINDINGS: UDP patients represented 36% of
      the whole group. Primary tumour location was significantly different between the
      two groups (p=0.001). Although the lung was the most frequent primary tumour
      location in both groups (UDP: 60%, DP: 43%), in UDP 14% only of the primaries
      were found outside of the lung and as much as 26% remained unknown despite
      thorough investigations. CONCLUSIONS: Our study confirmed the hypothesis that the
      relative frequency of primary tumours differs between DP and UDP patients. This
      difference therefore mandates a diagnostic strategy specifically tailored for UDP
      patients: if a radiological lung investigation clearly remains the best initial
      step in the work-up of these patients, extensive paraclinical investigations
      without a clear clinical suspicion should probably not be undertaken if this
      first survey fails to disclose the primary tumour as only 14% of the patients
      will actually benefit from it. In this situation, a neurosurgical procedure
      should probably be considered the most appropriate next step to be taken in order
      to provide a definitive diagnosis without unnecessary delays.

PMID- 14963748
TI  - Decompressive craniectomy with lattice duraplasty.
AB  - A method of opening dura for decompressive craniectomies is described. Numerous
      cuts intersecting in a lattice pattern allow the dura to expand in a gradual and
      controlled manner minimising the chances of cortical laceration or venous kinking
      on the craniectomy edge.

PMID- 14963749
TI  - Magnetic resonance artifact induced by the electrode Activa 3389: an in vitro and
      in vivo study.
AB  - BACKGROUND: The electrode Activa 3389 is widely implanted for deep brain
      stimulation (DBS) and MRI is often used to control the position of the electrode.
      However, induced distorsion artifacts may result in imprecise localization and
      may lead to misinterpretations of the clinical effects and mechanisms of DBS.
      METHODS: In vitro 3D MR study: the proximal and distal contacts of one electrode
      were spotted by two localizers. The maximal artifact height (MAH) and width (MAW:
      measured on distal contact), and the distances between the artifact and the
      localizers (proximal, distal and lateral) were measured on 2 transverse and
      sagittal MR sequences with 90 degrees rotation of frequency-encoded gradient and
      phase direction. In vivo 3D MR study: coronal and sagittal reconstructions along
      the main axis of the electrode were performed on 10 postoperative MR (20
      electrodes) to measure MAH and MAW. A Student t test was used to compare in vitro
      and in vivo measurements. FINDINGS: In vitro study: A MAH of 10.35 mm (+/-0.23)
      and MAW of 3.6 mm (+/-0.2) were found. We measured symmetrical extensions of the
      artifact over the distal contact. In vivo study: A MAH of 10.36 mm (+/-0.44) and
      MAW of 3.56 mm (+/-0.30) were obtained. No significant different artifact
      dimensions were measured between in vitro and in vivo studies (p<0.0001).
      INTERPRETATION: Precise 3D localization of the electrode in implanted patients is
      provided by MR identification of the limits of the distal contact artifact. The
      position of the other contacts is deduced given the size of the contacts and the
      intercontact distance.

PMID- 14963750
TI  - Spontaneous resolution of lumbar vertebral eosinophilic granuloma.
AB  - Eosinophilic granuloma (EG) is a rare disease but is more common in adults than
      children. It's often self-limiting. Spinal involvement is rare. It is the
      localized and most benign form of Langerhans' cell histiocytosis (previously
      known as histiocytosis X), characterised by lytic lesions in one or more bones.
      Spontaneous resolution of vertebral body lesions is very rare. In this case, the
      patient had one EG in a cervical vertebra and a similar lesion in a lumbar
      vertebra. This case is important because it featured a symptomatic lesion in the
      cervical spine accompanied by an asymptomatic lesion in a lumbar vertebra. We
      treated the cervical lesion by surgical fusion and followed the lumbar lesion up
      conservatively, with the patient in a corset. After 8 years of follow-up, control
      MRI showed that the lumbar lesion had spontaneously resolved.

PMID- 14963751
TI  - One stage removal of periaqueductal glioma in adult via infratentorial
      supracerebellar and transaqueductal approaches.
AB  - Most cases of periaqueductal tumours were found in children and adolescents, so
      treatment modalities in adults are not evaluated yet. A case of 40 years old
      woman with tectal and periaqueductal protoplasmatic astrocytoma grade II with
      history of headache and episodes of syncope is described. MRI showed
      triventricular hydrocephalus. After a shunt procedure she was doing well for
      about 15 months. Then she became somnolent, disoriented, and Parinaud syndrome
      appeared. The solid tumour was resected microsurgically in one stage. A part of
      it was removed via the supracerebellar infratentorial approach and tectal plate
      incision. The remainder of the tumour was removed through the fourth ventricle
      and the aqueduct which was filled by tumour mass. Postoperatively bilateral
      ptosis, vertical gaze palsy, slight horizontal gaze limitation and pupilloplegia
      were the main neurological sequelae. They all almost completely resolved within a
      year. The patient is doing well two and half years after the surgery. MRI showed
      patency of the aqueduct and no residual tumour. The authors suggest, that direct
      surgical attempt at total tumour removal should be considered in cases of
      periaqueductal and tectal gliomas. They also believe it is the first described
      case, in whom this type of tumour was totally removed by a combined transtectal
      and transaqueductal route.

PMID- 14963752
TI  - Syringomyelia caused by cervical spondylosis.
AB  - Syringomyelia is generally associated with Chiari type malformations, spinal
      tumors, or spinal trauma. Cervical spondylosis is only rarely involved. We here
      present a case of a 64-year-old woman with severe radicular pain in the right arm
      and the syringomyelic syndrome. Lateral radiographs of the cervical spine
      demonstrated spondylotic change at the C4/5 and C6/7 levels, and instability at
      C4/5. Dynamic magnetic resonance (MR) imaging revealed the spinal cord to be
      compressed at C5 and C6 with the body in extension, and the syrinx extended from
      C2 to the Th3 level on sagittal images. It was reduced remarkably after anterior
      decompression and stabilization at C4/5 and C6/7, and her symptoms also improved
      after surgery. We concluded that the syrinx in this case might have developed due
      to craniospinal pressure dissociation caused by intermittent spinal cord
      compression.

PMID- 14963753
TI  - Recurrent intracranial esthesioneuroblastoma outside the initial field of
      radiation with progressive dural and intra-orbital invasion.
AB  - A 55-year-old man presented with esthesioneuroblastoma in the right paranasal
      sinuses and orbita, extending into the right anterior and middle cranial fossa.
      He received a partial resection of tumour and post-operative radiotherapy, which
      was set with a central focus on the right orbit. Five years later, he came to our
      hospital with a complaint of left exophthalmos. Neuro-imaging revealed that the
      tumour recurred on the opposite side of the primary lesion, which was out side
      the irradiated field, with progressive invasion of the left temporal dura. The
      residual tumour in the irradiated field had reduced in size. He received gross
      total resection and post-operative radiotherapy. We would like to emphasize that
      radiotherapy is an important adjuvant therapy for esthesioneuroblastoma, and that
      the field setting for radiation therapy is extremely important.

PMID- 14963754
TI  - Inflammatory thromboembolic complication after craniopharyngioma surgery?
AB  - Aside from endocrine or visual disturbances an appearance of other complications
      after craniopharyngioma surgery is rare. We report a case of delayed brain
      infarction in the postoperative period of craniopharyngioma resection. A 30-year
      old man presented with visual impairment and diabetes insipidus. Imaging revealed
      a partly cystic, partly contrast enhancing intra-/suprasellar mass lesion. The
      patient underwent craniotomy with resection of the tumour. Histological
      examination revealed an adamantinomatous craniopharyngioma. Early postoperative
      an aseptic meningitis, which was diagnosed clinically as well as by laboratory
      and CSF analysis, resolved spontaneously. One week later a cerebral incident with
      infarction in the peripheral territory of MCA on the left side occurred. For this
      unusual event with a review of the literature a thromboembolic origin is
      suggested on the basis of inflammatory vascular involvement after an attack of
      aseptic meningitis.

PMID- 14963755
TI  - Spontaneous resolution of a Chiari I malformation associated syringomyelia in one
      child.
AB  - A child with complete spontaneous resolution of a Chiari I malformation
      associated Syringomyelia without surgical intervention is presented. The child
      was followed clinically by serial magnetic resonance imaging (MRI) and remains
      neurologically stable after 8-years of follow-up. To our knowledge, only 6
      pediatric cases with spontaneous resolution of a spinal cord syrinx documented by
      MRI without surgical intervention have been reported. This case is of interest in
      the light of the postulated theories to explain spontaneous resolution of
      syringomyelia.

PMID- 14963756
TI  - Hyperacute epidural haematoma isodense with the brain on computed tomography.

PMID- 14963757
TI  - Spinal epidural rhabdomyosarcoma.
AB  - We report an extremely rare case of rhabdomyosarcoma in the lower cervical and
      upper thoracic spine. The MR imaging appearance of the lesion was nonspecific,
      and different from the one previously reported. The majority of the tumor was
      removed surgically less than a month from the onset of symptoms. Treatment was
      continued with spinal irradiation and chemotherapy, however diffuse
      leptomeningeal metastases were found six months later.

PMID- 14963758
TI  - Successful management for spontaneous intracranial haemorrhage under critical
      thrombocytopenia (platelets < 1000/mm(3)) due to adolescence-onset idiopathic
      thrombocytopenic purpura.

PMID- 14963759
TI  - Comments on "The impact of the International Subarachnoid Aneurysm Treatment
      Trial (ISAT) on neurosurgical practice".

PMID- 14963762
TI  - Polyarteritis nodosa in a case of familial Mediterranean fever.
AB  - We describe a 7-year-old boy with familial Mediterranean fever (FMF) complicated
      by polyarteritis nodosa (PAN) with distinct angiographic findings. On admission,
      he had abdominal pain, arthralgia, and severe fibromyalgia. During
      hospitalization, he displayed maculopapular eruptions, high blood pressure,
      gastrointestinal bleeding, and persistent constitutional symptoms mimicking a
      vasculitic process, most probably PAN. Renal angiography showed a perfusion
      defect compatible with a renal infarction secondary to a vasculitic process. He
      responded well to pulse methylprednisolone therapy with colchicine. We emphasize
      the rare association of FMF and PAN and the non-aneurysmal angiographic signs of
      PAN.

PMID- 14963763
TI  - Surveillance of Epstein-Barr virus infection as a risk factor for post-transplant
      lymphoproliferative disorder in pediatric renal transplant recipients.
AB  - Post-transplant lymphoproliferative disorder (PTLD) represents a heterogeneous
      group of abnormal lymphoid proliferations, generally of B-cells, that occur in
      the setting of ineffective T-cell function because of pharmacological
      immunosuppression after organ transplantation. The vast majority of PTLDs are
      associated with Epstein-Barr virus (EBV) infection, as manifested by the presence
      of EBV within the malignant tissue. Surveillance for the presence of primary or
      reactivated EBV infection may have the potential to prevent the development of
      PTLD by early intervention. However, there are, at present, no means of
      discriminating between innocent infectious mononucleosis syndromes and PTLD.
      Furthermore, standardization of measurement of EBV copies between centers is
      urgently required for the definition of "high" EBV viral load. Because of a lack
      of a close relationship between viral load and the occurrence of PTLD, other
      strategies such as the combined analysis of EBV viral load and EBV-specific T
      lymphocytes may be better to assess the risk for the development of PTLD. Whereas
      the mainstay of therapy for overt PTLD is reduction of immunosuppression, such
      reduction based solely on a high EBV viral load without clinical evidence for
      PTLD is not based on scientific evidence. This strategy could result in the under
      immunosuppression of many transplant recipients in the absence of a real risk for
      PTLD, with potentially harmful consequences such as an increased rate of acute
      rejection episodes.

PMID- 14963764
TI  - Adenotonsillar hypertrophy and post-transplant lymphoproliferative disorder in
      pediatric renal transplant recipients.

PMID- 14963765
TI  - Neonatal estrogenization leads to increased expression of cellular retinol
      binding protein 2 in the mouse reproductive tract.
AB  - Exposure to estrogenic substances during a time window, the so-called "critical
      period," in perinatal life causes an irregular development of the genital tract
      that leads to ovary-independent proliferation and cornification in the vaginal
      epithelium in mice. We have previously demonstrated that retinol inhibits the
      irreversible effects of estrogen on the vagina. Here, mice kept in a vitamin-A
      deficient condition during perinatal life were shown to be more sensitive to the
      harmful effects of estrogen. In addition, expression of mRNA for retinol binding
      protein type 2 (CRBP2), a "small intestine-specific" cytosolic protein that
      captures intracellular retinal and retinol, was detected in the vaginal
      epithelium. Induction of increased expression of CRBP2 mRNA by estrogen was also
      evident in the uterus and epididymis. Both estradiol-17beta and
      diethylstilbestrol markedly increased the tissue content of CRBP2 mRNA in the
      vagina and uterus during the neonatal "critical period" but not after 15 days of
      age. These results taken together imply that estrogen disrupts the local vitamin
      A balance by an induction of CRBP2 gene expression in the epithelium in the
      developing mouse genital tract, and that retinoid imbalance may contribute to the
      genesis of irreversible effects of estrogen on the vagina.

PMID- 14963766
TI  - Excessive apoptosis of guinea pig colonocytes may lead to an imbalance between
      phagocytosis and degradation in vivo.
AB  - The success or failure of the clearance of apoptotic cell remains depends on the
      ability of phagocytic cells to recognize, phagocytoze, and digest these remains
      prior to their lysis, which would cause tissue inflammation. We have recently
      shown that, after mass-induced apoptosis of guinea pig colonocytes in vivo,
      phagocytosis by resident macrophages, although efficient, does not prevent a pre
      inflammatory response of the mucosa. The present study has investigated the
      cause(s) of this clearance failure. Immunohistochemistry and transmission
      electron microscopy were applied. Antibodies directed against the epithelial
      plasma membrane protein E-cadherin, the lysosomal membrane protein LAMP-1, and
      the lysosomal matrix protease cathepsin-D were used. The results revealed that:
      (1) anti-E-cadherin labeled the membrane of epithelial apoptotic bodies
      internalized in macrophages, (2) double and triple labeling demonstrated that the
      anti-LAMP-1 and anti-cathepsin-D antibodies recognized and were co-localized in
      lysosomes and/or phagolysosomes in macrophages but left E-cadherin-positive
      structures unlabeled, (3) the more numerous were the E-cadherin-positive
      inclusions in macrophages, the smaller was the number of those that stained
      positive for lysosomal markers. In parallel with electron microscopy, these
      findings showed that not all apoptotic bodies phagocytozed by macrophages were
      subsequently digested, suggesting that the phagocytotic ability of these cells
      was not matched by their digestive capability.

PMID- 14963767
TI  - Acetate non-utilizing mutants of Arabidopsis: evidence that organic acids
      influence carbohydrate perception in germinating seedlings.
AB  - A phenotypic screen was employed to isolate Arabidopsis plants that are deficient
      in their ability to utilize or sense acetate. The screening strategy, based on
      resistance to the toxic acetate analogue monofluoroacetic acid, was adapted from
      one that has been used successfully to identify important metabolic and
      regulatory genes involved in acetate metabolism in fungi. Following conventions
      established from the fungal work, the mutants were called acn mutants for acetate
      non-utilization. Three highly resistant plant lines were the focus of genetic and
      physiological studies. Mutant acn1 appears to be a true acetate non-utilizing
      mutant, as it displays increased sensitivity to exogenous acetate. The progeny of
      the original acn2 mutant did not germinate, even in the presence of sucrose as an
      exogenous carbon source. The germination of seeds from the F3 generation depended
      on the sucrose concentration in the medium. Only a small proportion of seeds
      germinated in the absence of exogenous sucrose and in the presence of 100 mM
      sucrose, but up to 70% of seeds germinated on 20 mM sucrose. Mutant acn3
      exhibited sensitivity to exogenous sucrose, showing significant chlorosis on
      medium containing 20 mM sucrose, but no chlorosis when grown in the absence of
      exogenous sucrose. This phenotype was alleviated if acetate was provided. The acn
      mutants demonstrate that disrupting organic acid utilization can have profound
      affects on carbohydrate metabolism.

PMID- 14963768
TI  - Hypertriglyceridemia as an indicator of the severity of falciparum malaria in
      returned travelers: a clinical retrospective study.
AB  - To test the hypothesis that the magnitude of plasma triglyceride changes could be
      related to the severity of falciparum malaria, we performed a retrospective case
      control study from January 1999 to December 2000 among hospitalized patients with
      fever who were returning to France from the tropics. Plasma triglycerides were
      measured in patients with severe falciparum malaria ( n=13), mild falciparum
      malaria ( n=169), non- falciparum malaria ( n=20) and controls ( n=55).
      Triglyceride level was significantly higher in the malaria group than in controls
      [mean values were 2.17+/-1.43 mmol/l versus 1.30+/-0.70 mmol/l, respectively (
      P<0.0001)]. Triglyceride level was also significantly higher in severe than in
      mild malaria [4.78+/-1.93 mmol/l versus 1.94+/-1.11, respectively ( P<0.00001)].
      Hypertriglyceridemia (>1.80 mmol/l) was noted in all the patients with severe
      malaria, compared to 37% of patients with mild disease ( P<0.001). Although
      further studies are needed, these results define the relevance of
      hypertriglyceridemia as an indicator of the severity of falciparum malaria.

PMID- 14963769
TI  - Purification, characterization, and immunolocalization of paramyosin from the
      adult stage of Fasciola hepatica.
AB  - Paramyosin, a vaccine candidate in different helminthiases, was purified from the
      adult liver fluke Fasciola hepatica using two different procedures. The first
      started with a crude extraction of paramyosin in high-salt buffer followed by gel
      filtration chromatography and two precipitation-solubilization cycles; in the
      second, anion exchange chromatography replaced the gel filtration step. In both
      cases, the apparent molecular weight of the purified protein determined by sodium
      dodecyl sulfate gel electrophoresis under reducing and non-reducing conditions
      was 97 kDa and 200 kDa, respectively. The molecular weights were consistent with
      the presence of a dimeric protein linked by disulfide bridges. Western blot
      analysis showed that the dimeric and monomeric forms were both recognized by an
      antiserum raised against the F. hepatica 97 kDa band (alpha-FhPmy), and by an
      anti- Schistosoma mansoni paramyosin immune serum. Immunohistochemistry using
      alpha-FhPmy demonstrated the localization of paramyosin within the subtegumental
      muscle and in muscle cells surrounding the gut of adult parasites. We also
      observed labeling of extramuscular structures like testes, surface lamellae of
      the gut and the tegument of adult flukes.

PMID- 14963770
TI  - Transcription status of vaccine candidate genes of Plasmodium falciparum during
      the hepatic phase of its life cycle.
AB  - The CSP, EMP2/MESA, MSP2, MSP3, MSP5, RAP1, RAP2, RESA1, SERA1 and SSP2/TRAP
      genes of Plasmodium falciparum are vaccine candidates. The hepatic phase of the
      infection is of major interest due to the protection induced by immunization with
      radiation-attenuated sporozoites. We therefore performed RT-PCR experiments to
      determine whether these genes are transcribed during this phase. Whereas
      transcripts of the CSP gene were detectable only in sporozoites, transcripts of
      the MSP2, MSP5, RAP1, RAP2, SERA1 and SSP2/TRAP genes were present in both
      sporozoites and infected hepatocytes. Transcripts of the EMP2/MESA gene were
      detectable only in infected hepatocytes. Transcripts of the MSP3 and RESA1 genes
      were not detectable in sporozoites or in infected hepatocytes. Genes presently
      identified as being transcribed during the hepatic phase may be of interest with
      respect to the design of preventative vaccination strategies.

PMID- 14963771
TI  - Effects of toltrazuril and ponazuril on Hammondia heydorni (syn. Neospora
      caninum) infections in mice.
AB  - Mice infected with tachyzoites of Neospora caninum (syn.: Hammondia heydorni)
      must be pretreated with cortisone in order to show disease symptoms. This
      indicates the status of an opportunistic agent of disease. Toltrazuril was an
      effective curative agent.

PMID- 14963772
TI  - Effects of toltrazuril and ponazuril on the fine structure and multiplication of
      tachyzoites of the NC-1 strain of Neospora caninum (a synonym of Hammondia
      heydorni) in cell cultures.
AB  - Rhesus monkey kidney cell cultures were used to propagate tachyzoites of the NC-1
      strain of Neospora caninum (syn. Hammondia heydorni). The infected cell cultures
      were incubated for 4-12 h in media containing 0, 1, 10 or 100 microg/ml of either
      toltrazuril or ponazuril. The effects were studied by light and electron
      microscopy. Drug dosages of at least 30 microg/ml were needed to eliminate the
      parasites. Ponazuril was found (with respect to the reduction of the number of
      parasites) to be less effective at dosages of 30 microg/ml compared to
      toltrazuril. However, the damage to the tachyzoites being incubated in 30 microg
      toltrazuril or ponazuril seen by electron microscopy was so significant that it
      was surely lethal. The initial damage occurred within the apicoplast and the
      tubular mitochondrion in all cases,thus destroying two of the most important cell
      organelles.

PMID- 14963773
TI  - Microchip capillary electrophoresis-based genetic comparison of closely related
      cyathostomin nematode parasites of horses using randomly amplified polymorphic
      DNA polymerase chain reaction.
AB  - The microchip-based capillary electrophoresis technology represents a valuable
      recent development for the analysis of complex DNA banding patterns. We have used
      this technology for the differentiation of the closely related cyathostomin
      species Cylicocyclus elongatus and C. insigne from the horse. We found that the
      Agilent 2100 bioanalyser in combination with the DNA 7500 Lab Chip were suited to
      perform a phylogenetic DNA fingerprinting analysis of the parasite species
      studied. The analysis of the electrophoretic data was optimised and it was
      possible to resolve a phylogenetic tree where all 12 individual worms of the two
      Cylicocyclus species studied were assigned to their species as determined by
      microscopic identification based on morphological traits. Thus, our data
      indicated that the procedure described here provides an additional powerful tool
      that can be employed for species delineation of closely related strains or
      species, such as the two taxa of Cylicocyclus investigated in the present study.
      Furthermore, by determining the second internal transcribed spacer region of
      three and nine individual worms for C. elongatus and C. insigne, respectively,
      low intraspecific variations of only up to 0.3% were demonstrated.

PMID- 14963774
TI  - Improved quantification of Plasmodium exoerythrocytic forms in rodents.
AB  - The result of a Plasmodium sporozoite challenge is currently evaluated either by
      detecting the emergence or not of parasites in the blood, or by estimating the
      "prepatent period", which is the time between sporozoite inoculation and the
      appearance of parasites in the blood. This type of measurement is relatively
      rough and has given way to another method of measuring sporozoite infectivity,
      which is to enumerate the exoerythrocytic forms (EEF) by microscopic examination
      of liver sections. Up until now, two different methods have been proposed to
      calculate and estimate the number of Plasmodium EEF forms in the livers of
      infected rodents, both of which are unfortunately biased to some extent. Here, we
      propose a different method of calculation, which more faithfully reflects the EEF
      number in the liver. This method is based on the calculated mean number of
      consecutive liver sections in which a schizont appears, and is host related.

PMID- 14963775
TI  - [Impact of olanzapine on quality of life of patients with schizophrenia: one-year
      follow-up with the Seville Quality of Life Questionnaire].
AB  - INTRODUCTION: Our objective is to present the impact on quality of life of long
      term olanzapine treatment in a significant number of schizophrenics as determined
      by the Seville Quality of Life Questionnaire (SQLQ), an instrument that addresses
      the aspects that particularly affect these patients, and to evaluate the
      sensitivity of this instrument to the changes induced by this treatment. METHODS:
      Three hundred and seventy two patients with the diagnosis of schizophrenia as per
      the ICD-10 classification were evaluated in a 1 year prospective study after
      switching to olanzapine. The SQLQ, Lehman's structured interview and short
      version of the discapacity assessment scale were used to evaluate patient's
      subjective experience; in addition, other instruments were used to evaluate
      psychopathology. RESULTS: Significant increases in the scores of the favorable
      scale and decreases in the unfavorable scale of the SQLQ were found. There were
      also significant improvements in quality of life as measured with Lehman's
      structured interview. This improvement continued until the end of the 1 year
      follow-up after switching to olanzapine. Both instruments show a good
      correlation. Changes in psychopathology were also remarkable, including the
      negative symptoms. CONCLUSIONS: The SQLQ has proven to be a sensitive instrument
      to measure quality of life in schizophrenic patients treated with olanzapine. It
      focuses on aspects that are relevant for patients that were frequently overlooked
      by treating physicians. This drug has been proven to have a favorable subjective
      impact upon patients, besides improving psychopathology.

PMID- 14963776
TI  - [Temperament and Character Inventory Revised (TCI-R). Standardization and
      normative data in a general population sample].
AB  - INTRODUCTION: The revised version of the Temperament and Character Inventory (TCI
      R), a tool designed by C. R. Cloninger for the evaluation of the seven dimensions
      defined in his psychobiological model of personality, was translated and adapted
      to Spanish. The aim of the study was to obtain normative data and scales with T
      scores in a incidental sample of the general Spanish population. METHODS: After
      adaptation to Spanish, the tool was administered to 400 subjects from several
      areas of Spain. The sample is stratified according to age and gender according to
      the year 2001 Spanish population census. We have studied the differences between
      men and women and the association between age and dimensions. We have checked the
      normal distribution of the traits, and proceeded with the standardization and
      normalization of the scores. RESULTS: We present the mean and standard deviation
      according to sex for each of the main dimensions and subscales. The scores of the
      main dimensions obtained for general population according to gender show a normal
      distribution that has allowed us to standardize them into T-scores. The
      reliability of the dimensions is high. There are differences in the means
      depending on gender: women scored higher in Harm Avoidance, Reward Dependence and
      Cooperativeness. Men scored higher in Persistence. There were no high
      correlations between age and the dimensions. CONCLUSIONS: The Spanish version of
      the new TCI-R is an adequate tool for the study of personality dimensions of
      normal population.

PMID- 14963777
TI  - [Factors associated to urgent referral in a mental health center].
AB  - INTRODUCTION: In this paper we analyze the factors related with the urgent
      referral. METHOD: We analyze a sample of 718 patients who were seen for an
      initial medical visit during a one year period in a community mental health
      center (418 of whom were urgent patients and 300 programmed patients). Variables
      associated to the referral process, clinical variables and social adjustment are
      studied. RESULTS AND CONCLUSIONS: The urgent medical visit is associated to
      clinical importance, to people previously seen in the health system, to
      initiative by others and not by the patient, to diseases that cause dysfunction
      in the sociofamiliar environment, and to the subjective loneliness feeling. The
      data show very little agreement between the clinician in the mental health center
      and referral doctor evaluation.

PMID- 14963778
TI  - [Psychiatric or forensic doctors? Study of legal interventions in a mental health
      center of Madrid].
AB  - INTRODUCTION: Psychiatric compulsory admission means that a fundamental right,
      such as individual freedom, is restricted. This has been legally regulated in
      Spain by the January 7, 2000 Civil Procedure Law 1/2000. Since the 1990's in the
      capital of Madrid, based on the agreements reached between Court no. 30 and the
      representatives of the Regional Health Service, the psychopathological
      assessments of supposed incapacities on which the Court has issued compulsory
      admission authorizations are carried out by the psychiatrists of the mental
      health centers instead of by the forensic physicians. MATERIAL AND METHODS: This
      study compares the first 60 cases evaluated in a mental health center during the
      years 1992-1994 with the last 60 cases of patients evaluated during the years
      2000-2002. RESULTS: In the second group, we found a significant increase in mean
      age and in the number of request for intervening in female patients. In addition
      to the number of request for civil disabilities and ordinary authorizations for
      compulsory admission, there were eight cases of court subjection to treatment and
      two requests for of psychiatric analyses for civil procedure. In the second group
      the number of home interventions significantly decreased in contrast with the
      number of interventions developed in medical offices. Although there was the same
      number of admissions from both groups, 36%, 20% of patients had no indication for
      treatment or admission in the second group. At 5 months after discharge, we
      observed a 15% loss of patients from the first group and 20% from the second
      group. CONCLUSIONS: Action protocols must be created in this type of
      intervention, starting in the corresponding court and going to the teams which
      would develop the interventions, in order to safeguard the citizen's rights.

PMID- 14963779
TI  - [Eating disorders, sport practice and physical self-concept in adolescents].
AB  - INTRODUCTION: The expansion of eating behavior disorders (EBD) has made it
      necessary to carry out the work of detecting cases as well as explaining this
      phenomenon as much as possible with certain features of the subjects and the
      behavior habits, for example, the practice of sports. METHOD: A total of 740
      students between 12 and 16 years old, whose sport's activity was investigated,
      filled out the Eating Disorders Inventory (EDI). Part of this sample,
      specifically 180 subjects, also answered the recently made Physical Self-concept
      Questionnaire (PSQ). RESULTS: Prevalence rates of EBD greater than those found in
      previous studies are found; the risk of EBD has an inverse relationship with the
      practice of sports and a direct one with low score on the PSQ. CONCLUSIONS:
      Physical and sport education should have a decisive role in the prevention of
      EBD; educators must be provided guidelines and resources that can help them in
      this task.

PMID- 14963780
TI  - [Psychotherapy of personality disorders].
AB  - A review of classical psychodynamic concepts in the psychotherapy of personality
      disorders (PD) is carried out. New approaches, such as dialectic behavioral
      therapy or cognitive analytic therapy, are also studied. Whenever possible,
      evidence is given on the efficacy of these approaches. The article finishes with
      a PD by PD study of relevant psychotherapeutic issues.

PMID- 14963781
TI  - [Thyrotoxic psychosis: a case report].
AB  - The first step in the assessment of a patient who presents psychiatric symptoms
      is to discard somatic illness. We present a case of a patient whose symptoms
      began with confusion, behavior alterations and agitation, which were followed by
      psychomotor inhibition with visual hallucinations, with underlying
      thyrotoxicosis. In the discussion, we analyze the aspects to consider in order to
      detect similar cases and their treatment, since, although it is a rare form of
      presentation of hyperthyroidism, it should be taken into account due to the
      seriousness of the picture.

PMID- 14963782
TI  - [Rhabdomyolysis due to polydipsia in a patient with psychotic disorder].
AB  - Polydipsia is a frequent clinical entity in psychiatric patients, especially in
      those with a psychotic disorder. Acute episodes of polydipsia can produce
      important metabolic alterations and even coma and death. Psychogenic polydipsia
      is a underestimated diagnosis, due to multiple causal factors and an etiology
      that has not been clearly established. We present the case of a patient with
      psychiatric background who was seen due to a clinical situation of severe acute
      renal failure by high rhabdomyolysis that needed hemodialysis, due to acute
      polydipsia. We also review some of the epidemiological and clinical factors and
      etiopathogeny of the polydipsia. It is considered necessary to keep in mind the
      in mind the diagnosis of polydipsia in any psychiatric patient showing acute
      symptoms of confusion.

PMID- 14963783
TI  - [Differential diagnosis among depressive pseudodementia, frontal dementia and
      subcortical dementia: a case report].
AB  - Among the clinical entities that show cognitive impairments it may sometimes be
      difficult to reach a diagnosis. That is the case with the differential diagnosis
      among depressive pseudodementia, subcortical dementia without motor symptoms and
      predominantly frontal-mesial frontotemporal dementia. This current paper presents
      one clinical case that illustrates such difficulties. In the first place,
      clinical, neuropsychological and neuroimaging features as well as common features
      of these three disorders are described, after which the case, and evolution of
      the diagnostic process are described.

PMID- 14963785
TI  - Validation of the inflammatory bowel disease questionnaire IBDQ-D, German
      version, for patients with ileal pouch anal anastomosis for ulcerative colitis.
AB  - BACKGROUND AND AIMS: The inflammatory bowel disease questionnaire (IBDQ) is the
      standard instrument for assessment of health-related quality of life (HRQOL) in
      patients with inflammatory bowel diseases. It has not been validated for patients
      with ileal pouch anal anastomosis (IPAA) and ulcerative colitis (UC). METHODS: To
      determine acceptance (percentage of completed items), reliability (Cronbach's
      alpha of the IBDQ-D subscales) and convergent validity (correlations of the IBDQ
      subscales with the questionnaires used for validation) 61 patients with UC (age
      52.7 +/- 13.9 years; 47 % female, 53 % male) and IPAA completed the German
      (Competence Network IBD) version of the Inflammatory Bowel Disease Questionnaire
      (IBDQ-D), the Short Form Health Survey (SF-36) the Hospital Anxiety and
      Depression Scale German Version (HADS-D) and the Giessener Symptom List (GBB 24).
      Face validity was assessed by a physicians' and patients' panel. All 37 patients
      underwent endoscopy making it possible to differentiate between patients with and
      without pouchitis (discriminant validity). RESULTS: With 97.7 % completed items
      the acceptance was high. Cronbach's alpha value for the subscales ranged from
      0.71 to 0.93. Missing items covering extraintestinal manifestations of IBD were
      criticized by patients. The correlation coefficients with comparable subscales of
      other instruments ranged between 0.41 and 0.76. Patients with clinical pouchitis
      scored significantly lower in all subscales than patients without pouchitis (p <
      0.001). CONCLUSION: The IBDQ-D has good acceptance, reliability, convergent and
      discriminant validity, but limited face and construct validity in patients with
      IPAA and UC.

PMID- 14963786
TI  - Diagnostics of Helicobacter pylori infection in patients with peptic ulcer
      bleeding.
AB  - BACKGROUND: In peptic ulcer bleeding, the sensitivity of H. pylori tests, in
      particular of the rapid urease test (RUT), has been reported to be insufficient.
      AIM: To validate the RUT, serology and the urea breath test were carried out in
      patients with bleeding peptic ulcers, and to study the influence of H. pylori
      suppressive treatment (HpSuT), i. e., antibiotics and proton pump inhibitors.
      PATIENTS AND METHODS: 123 consecutive patients (mean age 65.5 years) with a
      relevant bleeding from gastric or duodenal ulcers were prospectively tested for
      H. pylori infection by directs tests (RUT, histology, culture, urea breath test)
      and by IgG serology as an indirect test. Positive H. pylori status was defined by
      positive histology or culture. RESULTS: In patients without HpSuT during the
      preceding four weeks (N = 83), the sensitivity and specificity of RUT was 94 and
      84 %, that of serology 83 and 68 % respectively. The sensitivity of urea breath
      test decreased from 82 to 60 % after even one day of HpSuT. In the overall group,
      the duration of HpSuT and preceding hospitalization were independent factors
      linked with negative results of all direct tests. CONCLUSIONS: In peptic ulcer
      bleeding, RUT combined with histology is an adequate diagnostic approach.
      However, false negative results have to be considered following even short-term
      HpSuT or hospitalization. Non-invasive diagnosis based on serology alone is
      inaccurate and should be complemented by the urea breath test prior to starting
      HpSuT.

PMID- 14963787
TI  - [Lipoma of the small bowel].
AB  - CLINICAL FEATURES: A 40-year-old female presented with chronic diarrhoea,
      intermittent abdominal pain, and melena. She reported of a 7 kg loss of weight
      within the preceding 6 weeks and showed signs of mild abdominal pain upon
      palpation of the right lower quadrant. Our clinical diagnosis was Crohn's disease
      or infectious gastro-enteritis as a CT scan showed thickening of the colonic wall
      in the right lower quadrant. However a previously performed ileocolonoscopy was
      normal. TECHNICAL EXAMINATIONS: Magnetic resonance imaging showed a thickened
      terminal ileum with extensive narrowing of the bowel lumen, in addition a polyp
      obstructing the lumen of the terminal ileum at 30 cm was detected during
      colonoscopy. THERAPY: The involved portion of ileum was resected.
      Intraoperatively an intussusception with the polyp forming the leading edge was
      found. Histological analysis led to the diagnosis "lipoma". Postoperatively the
      patient is now feeling well without any abdominal pain. CONCLUSION: Tumours of
      the small bowel are rare and are therefore often forgotten in the list of
      differential diagnoses of abdominal pain. If symptomatic, these tumours present
      mainly with uncharacteristic and unspecific signs, often leading to a delay in
      correct diagnosis as in the presented case. We therefore suggest that small bowel
      tumours should be considered at earlier stages in the differential diagnosis of
      unexplained abdominal pain in the middle-aged patient with signs of intestinal
      obstruction.

PMID- 14963788
TI  - A dermoid cyst in the greater omentum as a rare epigastric tumor.
AB  - A 36-year-old female presented with unspecific epigastric discomfort, without
      weight loss, night sweat or fever. Ultrasound and computed tomography showed a
      solid tumor with a diameter of 9 cm in the left upper abdomen, without any
      connection to the stomach, the pancreas or spleen. Laparoscopy showed a
      connection to parts of the greater omentum. Two days after laparoscopic resection
      the patient was discharged from hospital. Histology revealed the rare diagnosis
      of a dermoid cyst. A possible malignant degeneration of the tumor has to be
      considered, and therefore the tumor should be resected. Since the operation the
      patient is asymptomatic and without tumor recurrence.

PMID- 14963789
TI  - [Requirements and recommendations for performing endosonographies].
AB  - For improvement of quality the working group of the Society of Gastroenterology
      in Nordrhein-Westfalen (Germany) was engaged with the questions, which
      apparative, personal and training conditions for endoscopic ultrasound are
      useful. The following proposals were preliminarily presented at the annual
      Congress of the DGVS (German Society of Digestive and Metabolic Diseases) 2001.
      They are thought to be subject of discussion for guidelines to be elaborated by
      this national society.

PMID- 14963790
TI  - [Hemosiderosis in Chronic Hepatitis C: Should Venesection Precede Treatment with
      Interferon-alpha and Ribavirin?].

PMID- 14963791
TI  - [Current theraphy of oesophageal cancer].

PMID- 14963792
TI  - [Biopsy diagnosis of chronic hepatitis].

PMID- 14963793
TI  - [58th General Meeting of the DGVS in Nuremberg].

PMID- 14963794
TI  - [Business Meeting Report "Endoscopic Ultrasound", DGVS 2003, Nuremberg].

PMID- 14963799
TI  - [Assessing the work-role quality and its significance in predicting return to
      work].
AB  - Non-medical factors such as age, years of schooling, and job satisfaction play an
      important role in determining whether patients resume their work after
      rehabilitation treatment. One element is the way the work situation is perceived
      by the patient. Usually, aspects of strain or job concerns are assessed. But
      employment does also include positive and rewarding aspects, though, such as
      meaning or social contact. According to the concept of work-role quality,
      theoretically these are independent constructs: someone may perceive job concerns
      and job rewards at the same time. In this study a short questionnaire (FRQ-B),
      broadly adapted from Barnett, Davidson and Marshall (1991), measuring job
      concerns and job rewards was developed and administered to a sample of cardiac
      rehabilitation patients. Psychometric analysis shows the factorial validity,
      consistency and construct validity of the instrument. Prediction of the return to
      work status three months after discharge from rehabilitation could be achieved on
      the item and subscale level. The effect sizes were comparable to other
      significant variables (e. g. psychological status, NYHA-status, wish to work).
      Specificities vary from 30 to 60 percent. The best predictor seems to be the Fear
      Avoidance Belief Questionnaire (FABQ), assuming a causal relationship be-tween
      work and illness. An analysis of subgroups using the FRQ-B reveals patients who
      experience little job rewards as well as many job concerns as a group with a high
      risk of not returning to work. The results of this study demonstrate the
      importance of assessing work related variables when dealing with return to work
      after rehabilitation treatment. Interventions to change the perception of the
      working place situation should be initialized and focussed early in
      rehabilitation treatment. The need for further research integrating the concept
      of work-role quality is discussed.

PMID- 14963800
TI  - [Work-related stress and resources of psychosomatic patients compared to the
      general population].
AB  - Work-related stress is an important determinant of the development of
      psychosomatic complaints and of the success of psychosomatic treatments. In order
      to specify work-related stress and resources in relation to the general
      population, 461 consecutive inpatients in psychosomatic rehabilitation were
      compared to matched pairs (age, sex, occupational status) from a representative
      community survey, the German Socio-economic Panel (GSOEP). Psychosomatic
      inpatients reported overall higher work stress than their matched pairs of the
      general population, the rank order of the stress factors as well as
      sociodemographic and occupational determinants were comparable. Patients also
      rated resources lower than their matched pairs. They reported much higher strains
      due to conflicts with supervisors and found less support among their colleagues.
      The items studied are useful to describe work stress profiles of psychosomatic
      rehabilitation patients and serve as a basis for therapeutic work.

PMID- 14963801
TI  - [Cluster formation - an operationalization of rehabilitation success in
      rehabilitants with chronic low back pain].
AB  - To investigate the impact of the way of allocation for rehabilitation on
      rehabilitation success in patients with chronic low back pain it was necessary to
      define appropriate criteria of success. A multidimensional model of success is
      presented in this article. First, the outcomes of rehabilitation are described
      and statistically tested. No statistically or clinically relevant changes between
      pre and post measurements were found. For further analysis of predictors and
      group comparisons it is necessary to define multidimensional success. For this
      purpose, cluster analyses are introduced as a possible model, resulting in three
      groups of patients with differing outcomes, i. e.: 20 % patients with declined
      pain symptoms, 40 % patients without any changes, 40 % patients with increased
      symptoms. No impact of the way of allocation for rehabilitation could be
      verified.

PMID- 14963802
TI  - [Evolution of a quality assurance programme for physiotherapy schools - results
      of the first quality inspections].
AB  - In cooperation with the Hochrhein-Institute for Research in Rehabilitation (HRI),
      the Association for Assuring the Quality of Education in Physiotherapy Schools in
      Germany (ISQ) has developed a quality assurance programme for physiotherapy
      schools. It aims at assessing the quality of physiotherapy schools in Germany,
      and to award a quality seal based on compliance with defined criteria. First, a
      catalogue of quality features and criteria relevant for education in
      physiotherapy was developed. It is based on the analysis of questionnaires that
      had been sent to all German physiotherapy schools, to selected physiotherapists
      and leading physiotherapists in hospitals, to competent federal authorities, and
      to three school-classes with group discussions. The persons addressed named 360
      different quality features. They were collected in a catalogue, revised in a
      multi-stage Delphi procedure, and approved consensually. The final criteria were
      transformed into basic quality requirements, and formulated as a check-list.
      Assessment of the quality features is carried out by trained visitors. In
      addition, the satisfaction of students is assessed with a questionnaire. The
      results of the interviews and the questionnaires are fed back to the schools in a
      quality report. Schools meeting all basic quality requirements are awarded the
      seal of quality. The seal is valid for three years. Since January 2003, this
      procedure is available for all schools in Germany. Until September 2002, a
      pretest of visitations and student questionnaires had been carried out with 31
      member schools of the ISQ; according to the resulting quality reports, none of
      these schools would instantly be awarded the quality seal. In all, more than half
      of the schools do not meet 10 of the 42 basic criteria. Fundamental deficiencies
      have been found in the documentation pertaining to supervision of practical
      training. In terms of training, further training and professional development of
      their teachers and associated professors, needs for improvement could be shown in
      more than 66 % of all visited schools. Only 9 of 31 schools could produce a
      written syllabus. Additionally, the requirements of teachers conferences and
      equipment of libraries were not met by the majority. A general problem among the
      schools is inadequate documentation in many fields.

PMID- 14963803
TI  - [Need for and benefit of medical rehabilitation measures from a general
      practitioner's perspective].
AB  - With different methodological approaches (postal survey, case analyses and focus
      group discussions) we investigated the attitudes of general practitioners (GPs)
      regarding the need, demand and effectiveness of medical rehabilitative measures.
      General Practitioners have a rather positive attitude towards rehabilitation in
      general. Male GPs have a tendency to be more sceptical than female GPs. With
      regard to the different measures within the German system, GPs show a
      differentiated opinion. They see a high number of patients who have a good
      benefit, though their definition of benefit differs from the statutory criteria
      for needs and outcomes. Patients and GPs mostly agree in their estimation of the
      outcome. Recent political ideas on improvement of the rehabilitative system are
      discussed on the basis of the results.

PMID- 14963804
TI  - [Book 9 of the German social code - an interim balance].
AB  - Book 9 of the German Social Code, effective as of July 1, 2001, was designed to
      bring about fundamental improvements in the situation of people with disabilities
      or at risk of being disabled. Somewhat more than two years after having come into
      force an extensive hearing on political level took place concerning the
      translation into action of this code. At the same time the legislator is planning
      first amendments to the Code. The author draws an interim balance concerning the
      translation into action of Book 9 of the German Social Code. The main emphasis of
      this statement is on the establishment of common service points as well as on the
      state of the arrangement of common recommendations at the Federal Rehabilitation
      Council.

PMID- 14963806
TI  - [Intention-to-treat].
AB  - What is meant by intention-to-treat? Why should data be analyzed in controlled
      trials in a way that all participants are included in the group to which they
      were randomly assigned, regardless of whether they completed the intervention
      given to the group? In this Tutorial, the logic of the intention-to-treat
      principle is outlined. It is shown that study results may be biased by excluding
      patients post hoc thus producing spurious effects that do not exist in the
      population under study. The intention-to-treat strategy avoids this bias.

PMID- 14963807
TI  - ["The law of rehabilitation and participation - interim balance concerning book 9
      of the German social code"].

PMID- 14963808
TI  - X-linked mental retardation and autism are associated with a mutation in the
      NLGN4 gene, a member of the neuroligin family.
AB  - A large French family including members affected by nonspecific X-linked mental
      retardation, with or without autism or pervasive developmental disorder in
      affected male patients, has been found to have a 2-base-pair deletion in the
      Neuroligin 4 gene (NLGN4) located at Xp22.33. This mutation leads to a premature
      stop codon in the middle of the sequence of the normal protein and is thought to
      suppress the transmembrane domain and sequences important for the dimerization of
      neuroligins that are required for proper cell-cell interaction through binding to
      beta-neurexins. As the neuroligins are mostly enriched at excitatory synapses,
      these results suggest that a defect in synaptogenesis may lead to deficits in
      cognitive development and communication processes. The fact that the deletion was
      present in both autistic and nonautistic mentally retarded males suggests that
      the NLGN4 gene is not only involved in autism, as previously described, but also
      in mental retardation, indicating that some types of autistic disorder and mental
      retardation may have common genetic origins.

PMID- 14963809
TI  - Detection of stabilizing selection in favor of the Santa Cruz homokaryotype in
      Drosophila pseudoobscura populations from the high plateau of the Colombian
      Andes.
AB  - Chromosome 3 rearrangements were studied in five Drosophila pseudoobscura
      populations from the high plateau of the Colombian Andes. As in previous studies,
      the Santa Cruz and Tree Line rearrangements were predominant in these
      populations, but for the first time other rearrangements such as the Olympic,
      Cuernavaca and a rearrangement similar to the endemic Mexican Amecameca
      rearrangement were also discovered. Researchers in the early 1960's showed that
      Colombian D. pseudoobscura populations were not in accordance with Carson's
      theory. They found a special heterotic system in this geographically isolated
      population. Our current results do not support these findings but instead favor
      Carson's theory, because in practically all the populations studied the
      homokaryotype excess was close to fixation. These new results indicate that some
      stabilizing selective pressures in favor of the homokaryotypes (especially Santa
      Cruz) have appeared in the Colombian plateau during the last 10-12 years. These
      new changes may be related to deforestation and habitat destruction by human
      beings and/or climatic changes motivated by the El Nino phenomenon. Genetic
      heterogeneity between populations was not significant and there was no isolation
      by-distance between them, findings which are contrary to those observed in some
      North American populations and which show that the Colombian populations now have
      rigid genetic systems. The frequency of the Santa Cruz rearrangement was also
      found to have increased in some populations over the last few years.

PMID- 14963810
TI  - Evaluation of crosses of Holstein, Jersey or Brown Swiss sires x Holstein
      Friesian/Gir dams. 2. Female liveweights.
AB  - The liveweights of 100 females sired by Holstein (H), Jersey (J) or Brown Swiss
      (BS) bulls out of Holstein-Friesian x Gir dams of 1/2 to 3/4 Holstein-Friesian
      fraction were compared. The animals were kept in a single herd under the same
      management. The data were analyzed separately for four age categories by least
      squares techniques. The models for cows and heifers older than 18 months included
      the fixed effects of breed of sire, Bos taurus fraction, season of weighing, days
      in milk class (for cows only), pregnancy status class, year and the random effect
      of animal nested within breed of sire x B. taurus fraction subclasses. The models
      for younger heifers included the same effects except for lactation and pregnancy
      status. Based on 2937 observations, the mean weights for 0- to 6-month-old calves
      for the groups with H, J or BS sires were 88 +/- 1, 77 +/- 1 and 75 +/- 1 kg,
      respectively, the mean weights for 1-year-old heifers were 168 +/- 2, 159 +/- 2
      and 155 +/- 1 kg, for 2-year-old heifers, 327 +/- 4, 303 +/- 4 and 319 +/- 4 kg,
      for 3-year-old heifers, 380 +/- 5, 369 +/- 8 and 390 +/- 4 kg and for cows, 464
      +/- 3, 413 +/- 2 and 478 +/- 2 kg. Cubic growth curves, which were different in
      the three sire breed groups, satisfactorily explained the cow weight changes with
      age (R(2)>or=0.98). Maximum weight was attained at 7.8, 9.5 and 9.2 years in cows
      with H, J or BS sires. Although breed of sire effects were not significant in
      heifers (P>0.05), those with H sires were the heaviest up to two years of age.
      The females with BS or J sires had similar weights up to one year of age, but
      thereafter the former reached similar weights as the females with H sires and
      declined less after attaining the maximum weight. The cows with J sires were the
      lightest at all ages. Since previous results showed similar protein and fat
      yields per day of calving interval in the three breed of sire groups, it is
      suggested that the lighter J crosses may be more economic than the other groups
      on account of their likely lower feed maintenance costs.

PMID- 14963811
TI  - Cystic fibrosis in Uruguay.
AB  - We conducted clinical and genetic analyses of 52 cystic fibrosis (CF) patients in
      Uruguay, which is about half of the known affected individuals in the country. A
      relatively high proportion had a mild presentation, characterized by pancreatic
      sufficiency (28%), a strong pulmonary component (97%), and borderline sweat
      electrolyte measurements (25%). Mutational analysis of CF chromosomes
      demonstrated a relatively low incidence of the DeltaF508 allele (40%) and a large
      number of other cystic fibrosis conductance regulator mutations, with an overall
      detection rate of about 71%. Fifteen different mutations were detected in our
      patients: DeltaF508, G542X, R1162X, G85E, N1303K, R334W, R75Q, R74W, D1270N,
      W1282X, DeltaI507, 2789+5G-->A, R1066C, -816C/T, R553X, as well as RNA splicing
      variant IVS8-5T. This group of Uruguayan CF patients has some characteristics in
      common with other populations of similar origin (Hispanics), as well as some
      unique characteristics.

PMID- 14963812
TI  - The future of selection: individuality, the twin legacies of Lamarck & Darwin.

PMID- 14963813
TI  - Size of beef cows: early ideas, new developments.

PMID- 14963814
TI  - Inheritance of resistance to the root-knot nematode Meloidogyne javanica in
      lettuce.
AB  - Resistance to the root-knot nematodes Meloidogyne spp. would be a valuable
      attribute of lettuce Lactuca sativa L. cultivars grown in tropical regions. The
      looseleaf lettuce 'Grand Rapids' is resistant to both M. incognita and M.
      javanica. Resistance to M. incognita has a high heritability, under the control
      of a single gene locus, in which the 'Grand Rapids' allele, responsible for
      resistance (Me), has predominantly additive gene action, and has incomplete
      penetrance and variable expressivity. We studied the inheritance of the
      resistance of 'Grand Rapids' (P(2)) to M. javanica in a cross with a standard
      nematode-susceptible cultivar Regina-71 (P(1)). F(1)(Regina-71 x Grand Rapids)
      and F(2) seed were obtained, and the F(2) inoculated, along with the parental
      cultivars, with a known isolate of M. javanica to evaluate nematode resistance. A
      high broad sense heritability estimate (0.798) was obtained for gall indices.
      Class distributions of gall indices for generations P(1), P(2), and F(2) were in
      agreement with theoretical distributions based on a monogenic inheritance model
      for the range of assumed degrees of dominance between approximately -0.20 and
      0.20. M. javanica resistance appears to be under control of a single gene locus,
      with predominantly additive gene action. Whether or not the Grand Rapids allele
      imparting resistance to M. javanica is the same Me allele imparting resistance to
      M. incognita remains to be determined.

PMID- 14963815
TI  - Rapid identification of single nucleotide polymorphisms by fluorescence-based
      capillary electrophoresis.
AB  - We describe the application of two different fluorescence-based techniques (ddNTP
      primer extension and single-strand conformation polymorphism (SSCP)) to the
      detection of single nucleotide polymorphisms (SNPs) by capillary electrophoresis.
      The ddNTP primer extension technique is based on the extension, in the presence
      of fluorescence-labeled dideoxy nucleotides (ddNTP, terminators), of an unlabeled
      oligonucleotide primer that binds to the complementary template immediately
      adjacent to the mutant nucleotide position. Given that there are no unlabeled
      dNTPs, a single ddNTP is added to its 3' end, resulting in a fluorescence-labeled
      primer extension product which is readily separated by capillary electrophoresis.
      On the other hand, the non-radioisotopic version of SSCP established in this
      study uses fluorescent dye to label the PCR products, which are also analyzed by
      capillary electrophoresis. These procedures were used to identify a well-defined
      SNP in exon 7 of the human p53 gene in DNA samples isolated from two human cell
      lines (CEM and THP-1 cells). The results revealed a heterozygous single-base
      transition (G to A) at nucleotide position 14071 in CEM cells, proving that both
      fluorescence-based ddNTP primer extension and SSCP are rapid, simple, robust,
      specific and with no ambiguity in interpretation for the detection of well
      defined SNPs.

PMID- 14963816
TI  - Further phenotypic characterization of pso mutants of Saccharomyces cerevisiae
      with respect to DNA repair and response to oxidative stress.
AB  - The sensitivity responses of seven pso mutants of Saccharomyces cerevisiae
      towards the mutagens N-nitrosodiethylamine (NDEA), 1,2:7,8-diepoxyoctane (DEO),
      and 8-hydroxyquinoline (8HQ) further substantiated their allocation into two
      distinct groups: genes PSO1 (allelic to REV3), PSO2 (SNM1), PSO4 (PRP19), and
      PSO5 (RAD16) constitute one group in that they are involved in repair of damaged
      DNA or in RNA processing whereas genes PSO6 (ERG3) and PSO7 (COX11) are related
      to metabolic steps protecting from oxidative stress and thus form a second group,
      not responsible for DNA repair. PSO3 has not yet been molecularly characterized
      but its pleiotropic phenotype would allow its integration into either group. The
      first three PSO genes of the DNA repair group and PSO3, apart from being
      sensitive to photo-activated psoralens, have another common phenotype: they are
      also involved in error-prone DNA repair. While all mutants of the DNA repair
      group and pso3 were sensitive to DEO and NDEA the pso6 mutant revealed WT or near
      WT resistance to these mutagens. As expected, the repair-proficient pso7-1 and
      cox11-Delta mutant alleles conferred high sensitivity to NDEA, a chemical known
      to be metabolized via redox cycling that yields hydroxylamine radicals and
      reactive oxygen species. All pso mutants exhibited some sensitivity to 8HQ and
      again pso7-1 and cox11-Delta conferred the highest sensitivity to this drug.
      Double mutant snm1-Delta cox11-Delta exhibited additivity of 8HQ and NDEA
      sensitivities of the single mutants, indicating that two different
      repair/recovery systems are involved in survival. DEO sensitivity of the double
      mutant was equal or less than that of the single snm1-Delta mutant. In order to
      determine if there was oxidative damage to nucleotide bases by these drugs we
      employed an established bacterial test with and without metabolic activation.
      After S9-mix biotransformation, NDEA and to a lesser extent 8HQ, lead to
      significantly higher mutagenesis in an Escherichia coli tester strain WP2-IC203
      as compared to WP2, whereas DEO-induced mutagenicity remained unchanged.

PMID- 14963817
TI  - Estimates of heritability in a blanched asparagus population.
AB  - To estimate the heritability values of characters frequently used as selective
      criteria, 32 half-sib families obtained from selected plants of three populations
      of the asparagus variety Argenteuil were evaluated in a randomized complete block
      design. The following characters were measured: days to emergence of the first
      spear, number and diameter of spears, number of stalks, plant height and average
      weight. The values of realized heritability were estimated and were compared with
      those obtained by the parent-offspring regression method. Phenotypic correlation
      coefficients between the different variables were significant. The values of
      realized heritability for most of the variables were moderate to high (between
      0.18 and 0.68), except for days to emergence; lower values were obtained by the
      regression method. As there was a high degree of heritability, additive genetic
      factors contributed significantly to the genetic variance, which would allow the
      selection of phenotypically superior plants for asparagus improvement projects.

PMID- 14963818
TI  - Identification and characterization of polymorphisms at the HAS alpha1-acid
      glycoprotein (ORM*) gene locus in Caucasians.
AB  - Human alpha(1)-acid glycoprotein (AGP) or orosomucoid (ORM) is a major acute
      phase protein that is thought to play a crucial role in maintaining homeostasis.
      Human AGP is the product of a cluster of at least two adjacent genes located on
      HSA chromosome 9. Using a range of restriction endonucleases we have investigated
      DNA variation at the locus encoding the AGP genes in a group of healthy
      Caucasians. Polymorphisms were identified using BamHI, EcoRI, BglII, PvuII,
      HindIII, TaqI and MspI. Nonrandom associations were found between the BamHI,
      EcoRI and BglII RFLPs. The RFLPs detected with PvuII, TaqI and MspI were all
      located in exon 6 of both AGP genes. The duplication of an AGP gene was observed
      in 11% of the individuals studied and was in linkage disequilibrium with the TaqI
      RFLP. The identification and characterization of these polymorphisms should prove
      useful for other population and forensic studies.

PMID- 14963819
TI  - (Co)variance components, genetic parameters and annual trends for calf weights in
      a Brahman herd kept on floodable savanna.
AB  - (Co)variance components and genetic parameters were estimated for body weights of
      an elite Brahman herd under a designed, supervised management and genetic
      program, including strategic artificial insemination (AI). Restricted maximum
      likelihood methods were used with a univariate animal model for birth weight (BW)
      and a bivariate model for weaning weight (205-day weight, 205W) and 18-month
      weight (548-day weight, 548W). Models included random animal direct and maternal
      genetic effects, maternal permanent environmental effect (c2), and sex-year-month
      of birth-age of dam and genetic group (identified and unidentified paternity), as
      fixed effects. Analysis A1 included all calves and analysis A2 included only
      those with identified sires. Of the 8,066 calves born, 36% were progeny of AI,
      11% from single sire and 53% from multi-sire herds. They were born from 1985 to
      1998, from 2559 dams and 146 sires (78 identified). Estimates of direct, maternal
      and total heritabilities from A1 for BW, 205W and 548W were: 0.23, 0.07 and 0.30;
      0.08, 0.14 and 0.16; 0.16, 0.04 and 0.28, respectively. Corresponding estimates
      of direct maternal genetic correlations were 0.22, 0.07 and 0.86, and c2
      estimates were 0.04, 0.14 and 0.04, respectively. Estimates of direct and
      maternal genetic, and permanent environmental correlations between 205W and 548W
      were: 0.66, 0.70 and 1.00. Variances and genetic parameters from A1 and A2 were,
      in general, very similar. Estimates of phenotypic, and direct and maternal
      genetic trends per year from A1 were: 0.393, 0.004 and 0.003 kg (BW), 3.367,
      0.142 and 0.115 kg (205W), 1.813, 0.263 and 0.095 kg (548W). Estimates of direct
      and maternal genetic trends from A2 were: 0.033 and -0.002 kg (BW); 0.186 and
      0.276 kg (205W); 0.471 and 0.136 kg (548W). The modern selection methods that
      have been used recently should be continued, with emphasis on the improvement of
      cow efficiency for sustainable beef production on floodable savanna combined with
      improved pasture.

PMID- 14963820
TI  - Cassava, Manihot esculenta Crantz, genetic resources: origin of the crop, its
      evolution and relationships with wild relatives.
AB  - About 98 species of Manihot are known. All of them are native to the New World
      and are concentrated in four regions in Brazil and Central America. All the
      Manihot species so far examined have 2n = 36 chromosomes. Interspecific hybrids
      between cassava and its wild relatives show relatively normal meiosis, and
      further generations can be obtained. Electrophoresis shows affinity among wild
      species of different sections, and between some of them and cassava. Both
      polyploidy and apomixis may have contributed to speciation in this genus.
      Polyploidy produced genetic variability, while apomixis is responsible for
      perpetuating new hybrid types adapted to different environments. Cassava may have
      originated by hybridization between two wild Manihot species, followed by
      vegetative reproduction of the hybrid.

PMID- 14963821
TI  - New genomic resources for the honey bee(Apis mellifera L.): development of a deep
      coverage BAC library and a preliminary STC database.
AB  - We have constructed a bacterial artificial chromosome (BAC) library for a
      European honey bee strain using the cloning enzyme HindIII in order to develop
      resources for structural genomics research. The library contains 36,864 clones
      (ninety-six 384-well plates). A random sampling of 247 clones indicated an
      average insert size of 113 kb (range = 27 to 213 kb) and 2% empty vectors. Based
      on an estimated genome size of 270 Mb, this library provides approximately 15
      haploid genome equivalents, allowing >99% probability of recovering any specific
      sequence of interest. High-density colony filters were gridded robotically using
      a Genetix Q-BOT in a 4 x 4 double-spotted array on 22.5-cm2 filters. Screening of
      the library with four mapped honey bee genomic clones and two bee cDNA probes
      identified an average of 21 positive signals per probe, with a range of 7-38
      positive signals per probe. An additional screening was performed with nine aphid
      gene fragments and one Drosophila gene fragment resulting in seven of the nine
      aphid probes and the Drosophila probe producing positive signals with a range of
      1 to 122 positive signals per probe (average of 45). To evaluate the utility of
      the library for sequence tagged connector analysis, 1152 BAC clones were end
      sequenced in both forward and reverse directions, giving a total of 2061
      successful reads of high quality. End sequences were queried against SWISS-PROT,
      insect genomic sequence GSS, insect EST, and insect transposable element
      databases. Results in spreadsheet format from these searches are publicly
      available at the Clemson University Genomics Institute (CUGI) website in a
      searchable format (http://www.genome.clemson.edu/projects/stc/bee/AM__Ba/).

PMID- 14963822
TI  - No evidence for minority male mating advantage in wild type strains of Drosophila
      ananassae tested in multiple-choice experiments.
AB  - Minority male mating advantage was tested in wild type strains of Drosophila
      ananassae through multiple-choice experiments. Mating success of two types of
      flies present in five different ratios was scored by direct observation in an
      Elens-Wattiaux mating chamber. We found no evidence for minority male mating
      advantage in wild type strains of D. ananassae. The relative mating success of
      two types of females was also compared in the multiple-choice experiments at
      different ratios; there was no evidence for a rare female effect. Further, there
      was similarity in the results of experiments employing different methods. The
      total number of homogamic and heterogamic matings was obtained by combining the
      data (all five ratios) from each experiment. Homogamic matings were significantly
      more frequent than heterogamic ones, which demonstrates preferential mating
      between males and females of the same strain; this was also supported by a lower
      isolation estimate. There was also a significant difference in the degree of
      mating preference between the two strains.

PMID- 14963823
TI  - Growth hormone mRNA expression in the pituitary of Bos indicus and Bos taurus x
      Bos indicus crossbred young bulls treated with recombinant bovine somatotropin.
AB  - The effects of breed and of recombinant bovine somatotropin (rbST) treatment on
      growth hormone gene expression were studied in young bulls. The experiment was
      completely randomized in a [2 x 2]-factorial arrangement, using two levels of
      rbST (0 or 250 mg/animal/14 days), and two breed groups (Nelore and Simmental x
      Nelore crossbred). A cDNA encoding Bos indicus growth hormone was cloned and
      sequenced for use as a probe in Northern and dot blot analyses. Compared to the
      Bos taurus structural gene, the Bos indicus cDNA was found to begin 21 bases
      downstream from the transcription initiation site and had only two discrepancies
      (C to T at position 144-His and T to C at position 354-Phe), without changes in
      the polypeptide sequence. However, two amino acid substitutions were found for
      Bubalus spp., which belong to the same tribe. The rbST treatment did not change
      any of the characteristics evaluated (body and pituitary gland weights, growth
      hormone mRNA expression level). Crossbred animals had significantly higher body
      weight and heavier pituitaries than Nelore cattle. Pituitary weight was
      proportional to body weight in both breed groups. Growth hormone mRNA expression
      in the pituitary was similar (P>0.075) for both breed and hormonal treatment
      groups, but was 31.9% higher in the pure Nelore group, suggesting that growth
      hormone gene transcription regulation differs among these breeds.

PMID- 14963824
TI  - Molecular characterization of ABC transporter-encoding genes in Aspergillus
      nidulans.
AB  - As a preliminary step towards characterizing genes encoding ATP-binding cassette
      (ABC) transporters that confer pleiotropic drug resistance in Aspergillus, we
      used a PCR-based approach to isolate four DNA fragments corresponding to
      different ABC type transporter genes. DNA sequencing and Southern blot analysis
      confirmed that they were distinct genes, which were designated abcA-D. One of
      these genes, abcD, was cloned and characterized. It was found to have a predicted
      1,452-amino acid translation product with a calculated molecular mass of 147,467
      kDa. The abcD gene specifies a single transcript of approximately 5.0 kb; there
      was a two- to six-fold enhancement of mRNA levels following exposure to
      miconazole, camptothecin, methotrexate, and ethidium bromide.

PMID- 14963825
TI  - Intraspecific variability of Bipolaris sorokiniana isolates determined by random
      amplified polymorphic DNA (RAPD).
AB  - Isolates of Bipolaris sorokiniana were analyzed by random-amplified polymorphic
      DNA (RAPD) techniques to determine the amount of intraspecific genetic
      variability and to study host-pathogen interactions. Ten isolates originated from
      different regions of Brazil were examined. Plants of the wheat cultivars BR8,
      BH1146 (original host) and IAC-5 Maringa, classified as resistant, moderately
      resistant or susceptible to B. sorokiniana, respectively, were inoculated with
      these 10 isolates. Twenty-seven isolates were recovered from these cultivars and
      were analyzed by RAPD assay and compared to the RAPD of the original 10 isolates.
      According to the RAPD profiles there was a high level of genetic variability
      among the isolates. We detected 69 polymorphic fragments, ranging from 1.6 to
      0.54 kb, in the original 10 isolates; 57 fragments with sizes between 1.98 and
      0.38 kb from the isolates recovered from BH1146; 47 polymorphic bands, ranging
      from 1.96-0.54 kb, were detected in the isolates from BR8 and 32 fragments
      between 1.98 and 0.42 kb in isolates were recovered from IAC-5 Maringa. The
      number of polymorphic fragments varied, even for the same isolate, when the
      isolates were recovered from different cultivar hosts.

PMID- 14963826
TI  - RAPD analysis of herbicide-resistant Brasilian rice lines produced via
      mutagenesis.
AB  - Over the last two decades, mutational techniques have become one of the most
      important tools available to progressive rice- breeding programs. In a mutation
      breeding program initiated in 1999 at the Instituto Agronomico of Campinas, SP,
      Brazil, a rice line, IAC103, was selected for mutational studies with gamma
      radiation and ethyl methyl sulfonate mutagenesis, with the aim of developing a
      herbicide-resistant crop. After mutagenesis, surviving plants were exposed to
      glufosinate to check for herbicide resistance, which was examined up to the
      second generation. A detailed RAPD analysis was made of the resistant plants.
      Eighty Operon technology primers were tested and 10 were selected for a detailed
      study of RAPD markers that could tag herbicide resistance genes. Resistant and
      susceptible lines produced variation in the RAPD patterns and certain bands were
      found only in certain lines. These results suggest genetic ligation that will be
      confirmed through a genetic segregation study.

PMID- 14963827
TI  - Female remating, sperm competition and sexual selection in Drosophila.
AB  - Female remating is fundamental to evolutionary biology as it determines the
      pattern of sexual selection and sexual conflict. Remating in females is an
      important component of Drosophila mating systems because it affects sperm usage
      patterns and sexual selection. Remating is common in females of many species of
      Drosophila in both natural and laboratory populations. It has been reported in
      many insect species and also in vertebrates. Female remating is a prerequisite
      for sperm competition between males, and the consequences of this competition,
      such as sperm precedence or sperm displacement, have been reported for many
      species of Drosophila. Female remating is dependent on the amount of sperm
      stored, the male seminal fluid components, nutrition, the quantity of eggs laid,
      experimental design and density of flies in laboratory. Remating by a female is
      an insurance against male sterility and sub-fertility and increases genetic
      heterogeneity of female offspring. Remating gives greater female productivity in
      many species of Drosophila. We examined female remating with respect to sperm
      competition and sexual selection in Drosophila and addressed the possible
      benefits for females. We also reviewed the role of accessory gland fluid in
      remating, costs associated with remating, the genetic basis of female remating
      and some possible mechanisms of sperm competition in the light of last male sperm
      priority and paternity assurance in Drosophila and other insects. We also suggest
      future areas of research.

PMID- 14963828
TI  - Transferrin polymorphism in Central Amazon populations of pescada, Plagioscion
      squamosissimus.
AB  - Blood plasma of 253 specimens from eight population samples of the sciaenid fish,
      pescada (Plagioscion squamosissimus), caught from four sites in the Central
      Amazon, was tested for molecular variants of transferrin. Starch gel
      electrophoresis was used to distinguish six species of transferrin molecules; 12
      of the 21 theoretically possible genotypes were found. There were highly
      significant departures from genetic equilibrium in seven of the eight population
      samples (chi-square (chi(2)) test for Hardy-Weinberg expectations) due to an
      excess of homozygotes and a corresponding deficiency of heterozygotes. A
      dendrogram based on UPGMA cluster analysis of genetic distances at the
      transferrin gene locus, estimated among the population samples and statistical
      analyses of the distribution of Tf allele frequencies, indicated three
      genetically discreet sub-populations of P. squamosissimus. The three sub
      populations, "Careiro/Iranduba", "Coari" and "Tefe", were found to have high
      frequencies of alleles Tf(2), Tf(4) and Tf(3), respectively. This genetic
      instability may be attributed to genetically discreet "allopatric stocklets",
      which diverged during past isolation.

PMID- 14963829
TI  - Decreased flight performance and sperm production in drones of the honey bee
      (Apis mellifera) slightly infested by Varroa destructor mites during pupal
      development.
AB  - We developed a bioassay to measure the flying power of drone, in order to
      determine which drones could reach a drone congregation area. A wind tunnel was
      used to test unparasitized drones and drones slightly parasitized by one or two
      mites during pupal development, and counts were made of the number of spermatozoa
      that they produced. Drones parasitized with one mite flew as long as control
      drones (x= 6'55" and 6'48", respectively, P = 0.512); however, those that had
      been infested by two mites flew significantly less (x= 2'16", P<0.001). There was
      a significant positive correlation (P<0.01) between flight duration and the
      number of spermatozoa per drone in control group (r = 0.53), and in both the one
      mite (r = 0.43) and two mite (r = 0.54) groups. Drones infested during
      development with one or two mites produced 24 and 45% fewer sperm, respectively.

PMID- 14963830
TI  - Frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms in a Brazilian population.
AB  - The glutathione S-transferase (GST) family of enzymes has a vital role in phase
      II of biotransformation of environmental carcinogens, pollutants, drugs and other
      xenobiotics. GSTs are polymorphic, with the type and frequency of polymorphism
      being ethnic dependent. Polymorphisms in GST genes have been shown to be
      associated with susceptibility to disease and disease outcome. We determined the
      frequencies of GSTM1, GSTT1 and GSTP1 polymorphisms in 591 volunteers who had
      been residents of Rio de Janeiro for at least six months. Blood was collected and
      DNA extracted by proteinase K/SDS digestion. Information about social habits and
      health problems was also recorded. GSTM1 and GSTT1 polymorphisms were analyzed by
      a PCR-Multiplex procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP.
      We found that 42.1% (48.9% of whites and 34.2% of non-whites) of the individuals
      had the GSTM1 null genotype, whereas 25.4% (25.1% of whites and 25.7% of non
      whites) had the GSTT1 null genotype. The genotypic distribution of GSTP1 was
      49.7% I/I, 38.1% I/V, and 12.2% V/V, whereas the allelic frequencies were 0.69
      for the Ile allele, and 0.31 for the Val allele. The frequencies of GST
      polymorphisms in this Brazilian population were found to be different from those
      observed in other populations, particularly of other South American countries.

PMID- 14963831
TI  - CENP-B is a conserved gene among vegetal species.
AB  - To explore the CENP-B centromere protein in beans, carrots, onions and potatoes,
      total RNA was isolated and reverse transcribed by PCR, and the cDNA encoding the
      CENP-B amino terminus domain amplified using CENP-B oligonucleotides. Blots
      containing PCR products were hybridized with a nick-translated pG/CNPB probe
      containing a complete human CENP-B gene. In all the plant species, anti-CENP-B
      antibodies recognized an 80-kDa protein. A 360-bp sequence encoding for the amino
      terminus region of the CENP-B protein was amplified by PCR in all the species and
      the nick translated pG/CNPB probe hybridized with the PCR products. Apparently
      the CENP-B centromere protein or an equivalent protein is widely distributed in
      the vegetal kingdom.

PMID- 14963832
TI  - Micronucleus investigation of alcoholic patients with oral carcinomas.
AB  - The micronucleus test (MN) is used as an indicator of genotoxic exposition, since
      it is associated with chromosome aberrations. An increased mutation rate in oral
      squamous cells, indicated by an increased MN frequency, is also related to the
      development of oral carcinomas. We evaluated the frequencies of MN and other
      metanucleated anomalies in the buccal squamous cells of 30 alcoholics with oral
      or oropharyngeal carcinomas, and compared them to a control group of abstinent
      health individuals. Microscopic examination was made of 2000 cells per individual
      from each of three distinct areas of the mouth: around the lesion (A), opposite
      to the lesion (B) and in the upper gingival-labial gutter (C); C was used as a
      control region because of low tumor frequency. There was a seven-fold increase in
      MN frequency in region B, a three-fold increase in region A and a two-fold,
      though nonsignificant, increase in C; indicating a gradient of frequencies
      towards carcinogenesis: C --> A --> B. Comparisons of frequencies of various
      types of metanucleated cells: binucleated, karyorrhexis (KR), karyolysis (KL) and
      broken egg (BE) in patients and controls showed, with few exceptions, highly
      significant differences. This gave us a better understanding of the dynamics of
      this squamous epithelium, supporting a more efficient biomonitor based on these
      various metanucleated anomalies: the repair index RI=(KL+KR)/(MN+BE). Also, the
      apparently contradictory results from regression analysis revealed that the MN
      frequency decreased with age and alcohol consumption, probably because of slow
      cell proliferation, and consequently led to a loss of homeostasis due to aging.
      In addition, in the analysis of nonparametric variables only one CAGE question
      was significant, confirming the effect of alcohol. In conclusion, the MN test and
      the repair index could be used for monitoring clinical evolution, by means of
      intra- and inter-individual cellular comparisons, in subjects with healed or
      surgically removed tumors or leukoplastic lesions, after chemo- or
      radiotherapeutic treatments.

PMID- 14963833
TI  - Greater genetic variability in Argentine Creole than in Thoroughbred horses based
      on serum protein polymorphisms.
AB  - Genetic polymorphism was analyzed for five blood proteins: albumin - Al, esterase
      - Es, alpha(1)B-glycoprotein - Xk, transferrin - Tf and hemoglobin - Hb in 200
      Thoroughbred (TB) and 124 Argentine Creole (AC) horses. Of the five systems
      examined, Tf and Hb were not in Hardy-Weinberg equilibrium in either breed and Es
      was not in equilibrium in the Creole breed. Genetic variability, estimated as
      average heterozygosity, was higher in AC (H = 0.585 +/- 0.131) than in TB (H =
      0.353 +/- 0.065). The genetic differentiation between these two populations
      (F(ST)) was 0.109. Thus, of the total genetic differences between breeds, the
      proportion of genetic variation attributable to breed differences was about 10%;
      the remaining 90% was due to individual variation within breeds. The high degree
      of genetic variability seen in Argentine Creole horses could be a consequence of
      natural selection. Selection of TB through the centuries has most likely modified
      the gene pool of the ancestral population, with a consequent reduction in
      variability at certain loci. Probably, different mechanisms exist for maintaining
      polymorphism at these loci in TB and in AC horses. Heterozygosity may have played
      a fundamental role in adaptation.

PMID- 14963834
TI  - Molecular detection of XO - Turner syndrome.
AB  - Turner syndrome is caused by haploinsufficiency of the short arm of X-chromosome,
      and is usually diagnosed by karyotyping. This procedure is time-consuming,
      expensive and unfeasible for population screening. We propose molecular detection
      of 45XO Turner patients based on the ability of HpaII, a methylation sensitive
      endonuclease, to induce the cleavage of non-methylated DNA in the active X
      allele. Genomic DNA was obtained from 22 patients with Turner syndrome confirmed
      by karyotype (45XO, N = 18; 45XO/46XX, N = 4). After digestion, DNA was amplified
      with primers directed to exon 1 of the androgen receptor (AR) gene and to the
      GAPDH control gene. Normal control females or mosaic patients, with a second
      methylated X-chromosome, escaped from HpaII digestion and produced a band
      corresponding to AR gene amplification. 45XO patients have just one active non
      methylated X-chromosome, completely digested by HpaII, thus preventing the
      amplification of the AR gene. Three of the 45XO cases gave amplified bands,
      suggesting low-frequency mosaicisms that are not detected by karyotyping.
      Compared to classical karyotype studies for the detection of 45XO Turner
      patients, this new molecular method is simpler, faster and less expensive.

PMID- 14963835
TI  - Inheritance of resistance to Meloidogyne incognita race 2 in the hot pepper
      cultivar Carolina Cayenne (Capsicum annuum L.).
AB  - Root-knot nematodes of the genus Meloidogyne are important pathogens affecting
      vegetable crop production in Brazil and worldwide. The pepper species Capsicum
      annuum includes both hot and sweet peppers; very little emphasis has been placed
      on breeding sweet peppers for nematode resistance. We report on the inheritance
      of resistance to Meloidogyne incognita (Kofoid & White) Chitwood race 2 in the
      hot pepper cultivar Carolina Cayenne. The hot pepper cv. Carolina Cayenne was
      used as seed parent and the sweet pepper cv. Agronomico-8 was used as pollen
      parent to obtain the F(1) and F(2) generations and the backcross generations
      BC(11) and BC(12). The plants were inoculated with M. incognita race 2 at a rate
      of 60 eggs/ml of substrate and, after a suitable incubation period, the numbers
      of root galls and egg masses per root system were evaluated on each plant. Broad-
      (0.77 and 0.72) and narrow-sense (0.77 and 0.63) heritability estimates were high
      for both root galls and egg masses, respectively. The mean degree of dominance
      was estimated as 0.29 and 0.25 for numbers of galls and egg masses, respectively;
      these estimates were not significantly different from 0, indicating a
      predominantly additive gene action. The results were consistent with a hypothesis
      of monogenic resistance in Carolina Cayenne.

PMID- 14963836
TI  - Inheritance of acylsugar contents in tomatoes derived from an interspecific cross
      with the wild tomato Lycopersicon pennellii and their effect on spider mite
      repellence.
AB  - Acylsugars present in Lycopersicon pennellii are responsible for the high levels
      of pest resistance often found in this wild tomato taxon. We investigated the
      inheritance of acylsugar contents in segregating populations of the interspecific
      tomato cross L. esculentum x L. pennellii and estimated correlations between
      leaflet acylsugar contents and the levels of mite repellence. Acylsugar contents
      were quantified with the Sommogy-Nelson colorimetric method in the acessions L.
      esculentum 'TOM-584' (P(1), low acylsugars), L. pennellii 'LA-716' (P(2), high
      acylsugars), in the interspecific F(1) (P(1) x P(2)) and in the F(2 )(P(1) x
      P(2)) generations. Mite resistance was assessed by a repellence test. Broad-sense
      heritability of acylsugar contents was moderately high (h(2)(b) = 0.476).
      Frequency distributions in the P(1), P(2), F(1) and F(2) can be explained by the
      action of a single major locus, with near-complete dominance of the L. esculentum
      allele for low-acylsugar content over the L. pennellii allele for high content.
      Indirect selection for high levels of acylsugars in leaflets led to correlated
      increases in the levels of mite repellency, indicating that acylsugars may be the
      main factor involved in mite resistance.

PMID- 14963837
TI  - Molecular cytogenetics in metaphase and interphase cells for cancer and genetic
      research, diagnosis and prognosis. Application in tissue sections and cell
      suspensions.
AB  - As the pioneer among molecular cytogenetics techniques, fluorescence in situ
      hybridization (FISH) allows identification of specific sequences in a
      structurally preserved cell, in metaphase or interphase. This technique, based on
      the complementary double-stranded nature of DNA, hybridizes labeled specific DNA
      (probe). The probe, bound to the target, will be developed into a fluorescent
      signal. The fact that the signal can be detected clearly, even when fixed in
      interphase, improves the accuracy of the results, since in some cases it is
      extremely difficult to obtain mitotic samples. FISH is still used mostly in
      research, but there are diagnostic applications. New nomenclature is being
      developed in order to define many of the aberrations that were not distinguished
      before FISH. Prenatal diagnosis of aneuploidies and malignancies are promptly
      detected with FISH, which is very useful in critical cases. In some tumors, where
      chromosomal abnormalities are too complicated to classify manually, the technique
      of comparative genomic hybridization (CGH), a competitive FISH, allows examiners
      to determine complete or partial gain or loss of chromosomes. CGH results allow
      the classification of many tumor cell lines and along with other complementary
      techniques, like microdissection-FISH, PRINS, etc., increase the possibility of
      choosing an appropriate treatment for cancer patients.

PMID- 14963838
TI  - A technique to obtain fibroblast cells from skin biopsies of living bats
      (Chiroptera) for cytogenetic studies.
AB  - We developed a procedure to obtain fibroblasts from bat skin. A small fragment of
      the ear is removed under ether anesthesia. This material is then cut up into
      small pieces and cultured in standard cell culture media. Very good quality
      chromosome preparations for cytogenetic studies are obtained in about three
      weeks. Secondary cultures can be used for other biological studies. This
      procedure does not require sacrificing the animals.

PMID- 14963839
TI  - Cell nucleus activity during post-embryonic development of Apis mellifera L.
      (Hymenoptera: Apidae). Intranuclear acid phosphatase.
AB  - We report nuclear acid phosphatase activity in the somatic (intra-ovariolar and
      stromatic) and germ cells of differentiating honey bee worker ovaries, as well as
      in the midgut cells of metamorphosing bees. There was heterogeneity in the
      intensity and distribution of electron dense deposits of lead phosphate,
      indicative of acid phosphatase activity in the nuclei of these tissues, during
      different phases of post-embryonic bee development. This heterogeneity was
      interpreted as a variation of the nuclear functional state, related to the cell
      functions in these tissues.

PMID- 14963840
TI  - Frequency of the hypervariable DNA loci D18S849, D3S1744, D12S1090 and D1S80 in a
      mixed ancestry population of Chilean blood donors.
AB  - Blood donors (N = 150) at San Jose Hospital (Santiago, Chile) were typed for one
      VNTR locus (D1S80) and three STR loci (D18S849, D3S1744, D12S1090). A
      questionnaire was used to determine the socioeconomic level of the donors,
      because it is known that some genetic markers (e.g., the ABO and Rh groups) are
      differentially distributed between different socioeconomic strata. This
      methodology revealed that two of the three socioeconomic strata distinguishable
      in Santiago were present in our sample of blood donors, with stratum II
      representing the middle strata and stratum III the low strata. Allele frequency
      was determined for each locus and socioeconomic stratum, and it was found that
      the allele distributions of each locus in socioeconomic strata II and III were
      statistically similar. All loci conformed to the Hardy-Weinberg law and there was
      no evidence for association between the alleles of the four loci, allelic
      frequencies being similar to those found in North American Hispanic populations.
      The results support the view that the analysis of these loci may have useful
      applications in population genetics as well as in identity tests.

PMID- 14963841
TI  - Apomixis and cassava.
AB  - Apomixis means seed formation without fertilization. In cassava (Manihot
      esculenta) it is an alternative to reproduction by cuttings, which normally
      transmits pathogens and leads to an accumulation of viral and bacterial diseases.
      Apomixis also assures preservation of heterosis and avoids genetic segregation.
      It occurs in wild relatives of cassava and has been transferred successfully from
      Manihot glaziovii and M. neusana. It is facultative, and occurs at a low
      frequency, ranging from 1-2%, and apparently is genetically different from
      apomixis in other crops. With selection, the frequency can reach 13%. Apomixis in
      cassava is frequently associated with aneuploidy but it does occur in some
      diploid types. It is due to the formation of aposporic sacs, which can easily be
      detected by clearing tissue preparations. Apomixis appears to have played an
      important role in speciation during the evolution of Manihot, since it leads to
      the maintenance and perpetuation of sterile interspecific hybridization. The use
      of apomixis in cassava breeding could lead to a boom in line improvement and
      commercial production. In addition to preserving superior genotypes, avoiding
      contamination of new plants, it would enable international programs to export
      their germplasm to destination countries. This would allow the use of superior
      genotypes even if apomixis occurs at a low frequency. A scheme to maximize
      benefits is to use diploid apomictic clones as maternal parents, which can be
      crossed with pollinators of polyploid interspecific hybrids, followed by
      selection among the progeny of new apomictic types that combine the heteroses of
      both interspecific hybridization and polyploidy. In addition, they acquire
      favored genes that have been transferred from the wild to the commercial crop.

PMID- 14963842
TI  - Varroa-tolerant Italian honey bees introduced from Brazil were not more efficient
      in defending themselves against the mite Varroa destructor than Carniolan bees in
      Germany.
AB  - In Europe and North America honey bees cannot be kept without chemical treatments
      against Varroa destructor. Nevertheless, in Brazil an isolated population of
      Italian honey bees has been kept on an island since 1984 without treatment
      against this mite. The infestation rates in these colonies have decreased over
      the years. We looked for possible varroa-tolerance factors in six Italian honey
      bee colonies prepared with queens from this Brazilian island population, compared
      to six Carniolan colonies, both tested at the same site in Germany. One such
      factor was the percentage of damaged mites in the colony debris, which has been
      reported as an indicator of colony tolerance to varroa. A mean of 35.8% of the
      varroa mites collected from the bottoms of the Italian bee colonies were found
      damaged, among which 19.1% were still alive. A significantly greater proportion
      of damaged mites were found in the Carniolan bees (42.3%) and 22.5% were
      collected alive. The most frequent kind of damage found was damaged legs alone,
      affecting 47.4% of the mites collected from debris in Italian bees, which was
      similar to the amount found in Carniolan colonies (46%). The mean infestation
      rate by the varroa mite in the worker brood cells in the Italian bee colonies was
      3.9% in June and 3.5% in July, and in drone brood cells it was 19.3% in June. In
      the Carniolan honey bee colonies the mean infestation rates in worker brood cells
      were 3.0 and 6.7%, respectively in the months of June and July and 19.7% in drone
      brood cells in June. In conclusion, the 'Varroa-tolerant' Italian honey bees
      introduced from Brazil produced lower percentages of damaged mites (Varroa
      destructor) in hive debris and had similar brood infestation rates when compared
      to 'susceptible' Carniolan bees in Germany. In spite of the apparent adaptation
      of this population of Italian bees in Brazil, we found no indication of
      superiority of these bees when we examined the proportions of damaged mites and
      the varroa-infestation rates, compared to Carniloan bees kept in the same apiary
      in Germany.

PMID- 14963843
TI  - Genotoxic evaluation of the organophosphorous pesticide temephos.
AB  - The chemical compound temephos (0,0,0',0'-tetrametyl-0,0'-thiodi-p-phenylene
      phosphorothioate) is an organophosphorous pesticide that has been used in Brazil
      since 1967 in control campaigns against the mosquito Aedes aegypti, the vector of
      dengue and yellow fever. We used single cell gel electrophoresis (SCGE), SOS/umu
      and Ames/Salmonella assays to test the toxicity and mutagenicity of temephos.
      Temephos was genotoxic in the SCGE assay, inducing severe DNA lesions (type IV
      lesions) at doses above 1.34 micro M. It was mutagenic, but not toxic, in the
      SOS/umu assay to Escherichia coli strain PQ37, but not to PQ35, at concentrations
      above 1.33 micro M, particularly when the S9 mixture was not used in the assay.
      Temephos was not mutagenic in the Ames assay with S. typhimurium strains TA97,
      TA98, TA100 and TA102, both with and without metabolic activation. However,
      temephos at concentrations above 3.33 micro M was mutagenic to TA98NR, YG7104 and
      YG7108, both with and without metabolic activation. In conclusion, temephos was
      genotoxic and mutagenic in all the three tests used, and in two of them at
      concentrations similar to those routinely used to combat Aedes aegypti.

PMID- 14963844
TI  - A model system for testing gene vectors using murine tumor cells on the
      chorioallantoic membrane of the chick embryo.
AB  - We developed a model system for testing gene vectors, based on the growth of
      murine tumors on the chorioallantoic membrane (CAM) of embryonic chickens. The
      ability of selected murine cells to grow on the CAM was rated according to the
      following criteria: i) formation of tumor masses; ii) metastasis formation; iii)
      reproducibility; iv) yield, indicated as the number of embryos surviving to
      assessment time with visible tumors on the CAM; v) maintainability of the cell,
      both in the original host and the embryonic chick, or 'shuttle maintainability';
      vi) detection by the naked eye, and vii) cost/benefit relation. The murine
      melanoma cell lineage, B16F10, which efficiently forms distinct, pigmented tumor
      masses and metastases on the CAM, performed better in this model than the murine
      B61 cell line. In vitro transduction of B16F10 cells with a recombinant
      adenovirus carrying a construct of the E. coli LacZ gene followed by inoculation
      onto the CAM resulted in beta-galactosidase expression in the tumor mass growing
      on the CAM. This model is potentially applicable to preclinical evaluation of
      gene vectors, especially for gene therapy of cancer.

PMID- 14963845
TI  - [Preliminary evaluation of a new screening test for dementia (Eurotest)].
AB  - INTRODUCTION: The changeover to the new currency has meant that the Money test, a
      screening test for dementia with a number of advantages over those currently
      available, is now of no use. AIMS: Our aim was to perform a preliminary
      evaluation of the Eurotest, which is a version of the Money test adapted to the
      new currency system. SUBJECTS AND METHODS:  DESIGN: phase I, diagnostic
      evaluation (convenience sampling; pre-test prevalence 50%). SUBJECTS: >65 years
      with no sensory deficit; 30 with mild dementia and 30 without dementia. METHOD:
      evaluation of socio-demographic variables and of mini-mental performance (MMSE),
      Pfeiffer's test (SPMSQ), the seven-minute test (7MT) and Eurotest. Statistical
      study: comparison between groups using t test and chi squared, depending on the
      variables; determination of diagnostically useful parameters and ROC curves, with
      their respective 95% confidence intervals; linear regression study with a step by
      step strategy. RESULTS: The groups did not differ as regards age, sex, level of
      schooling, degree of literacy, employment and knowledge of money systems. The
      Eurotest has a sensitivity of 0.93 (0.76-0.99) and a specificity of 0.87 (0.68
      0.96), which is similar to that of the MMSE and the 7MT. The Eurotest (6.77 +/-
      1.65 min) takes less time than the 7MT (8.87 +/- 1.81 min) and is not modified by
      the subject's clinical situation. The level of schooling does not affect the
      results of the Eurotest. CONCLUSIONS: The Eurotest is simple, quick, valid,
      useful and is unaffected by the level of schooling, which are features that make
      it a valid alternative to the tests currently available.

PMID- 14963846
TI  - [Voltage sources analysis in studies with foramen ovale electrodes].
AB  - INTRODUCTION: Paroxysmal activity in medial temporal lobe epilepsy is originated
      in either hippocampal or parahippocampal regions. This activity can be directly
      recorded by foramen ovale electrodes. That paroxysmal activity will start from
      irritative or ictal areas. However, anatomo-functional relations between both
      regions are still debated. OBJECTIVE: We describe a new physical very simple
      model which allows to directly analysis the anatomo-physiological relations
      between sources for interictal and ictal areas. RESULTS: 1) The mathematical
      model allows to fit with minimum error and great precision the voltage sources
      originated from monopoles. 2) We can obtain this degree of precision with a
      matrix using an internodal distance of 0.1 mm (300x200 nodes) 3) Triplets of
      potentials with double sources with equal or specially with inverse charges have
      bigger error than monopolar charges. 4) Fitting real data obtained from a patient
      shows an error of 0.29 +/- 0.17% for interictal and 0.54 +/- 1.22% and 2.84 +/-
      3.00% for two seizures (mean +/- SD). CONCLUSIONS: This model allows directly to
      know the relative anatomo-physiological relations between interictal and ictal
      sources in MTLE, which have a very important implications so for patho
      physiological as therapeutics and outcome implications.

PMID- 14963847
TI  - [Friedreich's ataxia: analysis of magnetic resonance imaging parameters and their
      correlates with cognitive and motor slowing].
AB  - INTRODUCTION: The heredodegenerative ataxias are a heterogeneous group of
      disorders affecting especially the cerebellum and its tracts. Magnetic resonance
      imaging (MRI) studies using quantitative methodology are scarce, particularly in
      Friedreich's ataxia (FA). On the other hand, slowness of information processing
      speed has been described in FA, but no empirical relation with MRI parameters has
      been established. OBJECTIVE: The aim of the present study was to quantitatively
      assess infra and supratentorial atrophy in patients with clinical diagnosis of FA
      and to establish the relationship with a information processing speed measure.
      PATIENTS AND METHODS: Twelve FA patients that fulfilled clinical diagnostic
      criteria and twelve control subjects were studied. A computerized system that
      differentiate reaction time and movement time, as well as a semiautomated
      technique of binarization and analysis of MRI were used. RESULTS: Patients showed
      a poorer performance in movement time and in reaction time. Analyzing the
      frequency of pathologic changes, vermal atrophy was present in 67% of the
      patients and cerebellar hemisphere atrophy in 50%. Only a minority of patients
      showed signs of supratentorial cerebral atrophy (17%). Statistically significant
      negative correlations were obtained between reaction time and the size of the
      cerebellum. CONCLUSIONS: Cerebellar hemisphere atrophy is a usual finding in FA,
      although vermal atrophy is more frequent. The relation between cerebellar atrophy
      and reaction time supports the claim about cerebellar involvement in the
      information processing and response speed.

PMID- 14963848
TI  - [Hypomelanosis of Ito. A possibly under-diagnosed heterogeneous neurocutaneous
      syndrome].
AB  - INTRODUCTION: Hypomelanosis of Ito (HI) or incontinentia pigmenti achromians is a
      multisystemic neurocutaneous disorder that is associated to neurological
      complications in a high percentage of patients. AIMS: The purpose of this study
      is to review the most significant features in a series of 14 patients with HI.
      PATIENTS AND METHODS: We conducted a retrospective study in which the following
      data were analysed: age, sex, familial and personal history, clinical features
      and complementary explorations that were carried out. We report the cases of nine
      females and five males aged between 4 months and 14 years. RESULTS: All the
      patients presented neurological anomalies, including psychomotor or mental
      retardation in 11 (associated to autistic behaviour in two of them),
      neuroradiological anomalies in seven, microcephalus in three and epileptic
      seizures in two. Other significant complications were musculoskeletal and ocular
      anomalies (each of which were present in nine patients), dental disorders in six,
      coarse facies and dysmorphic ears in four patients, hypoacusis in five and
      congenital heart disease in two. The following were also observed, but as
      isolated events: choanal atresia, cleft palate, segmental dilatation of the
      colon, cryptorchidism, inguinal hernia, low height, vesicoureteral reflux and
      premature pubarche. CONCLUSIONS: There is no biological marker that identifies HI
      and a number of clinical forms only appear in the skin in a very mild form, which
      means they sometimes going unnoticed or are not considered to be important enough
      to establish a diagnosis. This entity may, therefore, be more frequent than we
      think and its prevalence is perhaps underestimated.

PMID- 14963849
TI  - [Cognitive diagnosis of cerebrovascular disease by event related potentials:
      anatomical sources that generate P300].
AB  - INTRODUCTION: Cerebrovascular disease causes different cognitive alterations.
      There is a need to develop tools that are capable of diagnosing them. One of them
      could be event related potentials. These provide an indicator of cognitive
      processing in real time. PATIENTS AND METHODS: A study was conducted of 10
      patients with cerebral infarction in the frontal region and 10 paired healthy
      controls. Evaluation of the patients was performed a week after the stroke. A
      continuous performance test was applied to both groups together with the
      recording of the electrical activity in the brain in order to obtain the P300
      component. The results were submitted to the non-parametric Student's t test, and
      the Bayesian model averaging method (BMAM) was employed to calculate the sources
      generating the electrical activity recorded on the electroencephalogram. RESULTS:
      Patients displayed significantly poorer performances compared to the healthy
      controls in the attention test. The BMAM showed that the P300 component was
      related to the right hand temporal structures in healthy controls, whereas the
      left temporoparietal regions were also involved in the patients. CONCLUSIONS:
      These findings indicate the existence of subclinical disorders affecting
      sustained attention and that they can only be detected by very sensitive tools;
      furthermore, they also have implications for the brain circuits regulating
      sustained attention and the P300 component.

PMID- 14963850
TI  - [Arterial gas embolism progressing to a massive stroke].
AB  - INTRODUCTION: Arterial gas embolism (AGE) is a main iatrogenic complication
      resulting from the use of invasive procedures. It is difficult to diagnose if it
      is not clinically suspected. CASE REPORT: A 67-year-old male patient, with a
      history of interventions involving a mitral prosthesis and a double aortocoronary
      bypass, who visited Emergency room with symptoms of a high temperature and
      general malaise. He was canalised peripherally and the electrocardiogram (ECG)
      showed an auricular fibrillation that had already been detected. While under
      observation he suffered a loss of consciousness, generalised hypotonia,
      conjugated gaze deviation towards the right, lower left facial paralysis and left
      Babinski positive. A new ECG showed ST segment elevation in V2-V5. A cranial
      computerised tomography (CAT) scan with no contrast revealed a number of
      serpiginous images caused by the presence of air in vascular structures. A second
      cranial CAT scan showed the disappearance of the visible air and signs of
      ischemic stroke in the territory of the right middle and posterior cerebral
      arteries and the left middle cerebral artery. Clinical-radiological findings
      suggested an AGE in the brain with massive stroke and acute myocardial infarct
      with similar causation. CONCLUSIONS: It is not clear what caused the air embolism
      in this patient but it can most probably be explained by air accidentally
      entering a peripheral vein. Carrying out an early cranial CAT scan can provide us
      with a diagnosis and a later CAT scan can evaluate the consequences of the
      embolism.

PMID- 14963851
TI  - [Course and treatment of progressive subacute encephalopathy caused by human
      immunodeficiency virus in children. The value of Botulinum toxin].
AB  - INTRODUCTION: Progressive subacute encephalopathy due to human immunodeficiency
      virus (PSE-HIV) is an important cause of morbidity and mortality in perinatal HIV
      infection. Although current combined antiretroviral therapies do manage to check
      its progression, they often give rise to severe motor sequelae that are similar
      to the spastic infantile cerebral palsy resulting from other aetiologies. We
      present the case reports of four preschool age children suffering from this
      pathology who have benefited from long term treatment with botulinum toxin type A
      (BTA). CASE REPORTS: Four patients suffering from early onset PSE HIV, who
      responded well to combined antiviral therapies, and who had severe motor sequelae
      (two cases of tetraparesis and two spastic dysplegias), with no cognitive
      disorders. The multidisciplinary treatment of their motor disorder included six
      monthly sessions of muscular injections of BTA in the usual doses, with good
      results from the functional point of view and with no significant side effects.
      DISCUSSION: PSE-HIV is defined by one of the following criteria: acquired
      microcephalus, retarded neurological development or symmetrical motor
      involvement. It constitutes one of the most frequent diagnostic criteria of AIDS
      in patients infected by vertical transmission. An early diagnosis and treatment
      are fundamental for the patient's prognosis. Severe motor sequelae in the form of
      spastic infantile cerebral palsy are frequent. In our experience treatment of the
      spasticity associated to this entity with BTA has proved to be useful and safe,
      with a clear improvement in gait functionality.

PMID- 14963852
TI  - [Bilateral thalamic gliomas: report of a case with cognitive impairment].
AB  - INTRODUCTION: Bilateral thalamic tumours are very rare and have been recently
      identified as a subgroup of thalamic neoplasms due to their characteristic
      clinical presentation, with behavioural and memory disorders and without sensory
      or motor changes. We describe a patient who presented with mood and behaviour
      changes due to a bilateral thalamic glioma, discuss the literature related to
      these rare neoplasms and review the anatomical bases of their particular clinical
      presentation. CASE REPORT: A 67-year-old woman consulted because of behavioural
      changes and frequent forgetfulness. Neurological examination was normal except
      from a deficit in the retention of words and numbers. MR images revealed
      bilateral thalamic swelling by a isointense in T1, hyperintense in T2 and
      protonic density mass that did not enhance. The tumour was diagnosed as an
      astrocytoma by stereotactic biopsy. She continued to deteriorate and a year after
      diagnosis she was bedridden and with a severe dementia. CONCLUSION: Bithalamic
      tumors, as other lesions that affect the thalamus bilaterally, characteristically
      present with mood and behaviour changes and memory impairment.

PMID- 14963853
TI  - [Chiari type I malformation in a patient with bulbar onset amyotrophic lateral
      sclerosis].
AB  - INTRODUCTION: Diagnosis of amyotrophic lateral sclerosis (ALS) requires of the
      exclusion of several pathologies of the cranio cervical junction that mimic ALS.
      The importance of such exclusion is in fact sustained by the prognostic
      implications that ALS has. CASE REPORT: We report the case of a 58-year-old woman
      with bulbar onset sporadic ALS associated with Chiari type I malformation on the
      MRI of the craniocervical junction. At the time of consultation, ALS was
      clinically defined but some of the symptoms were contributed by cerebellar
      amygdala compression of the medulla. CONCLUSION: To our knowledge this is the
      first time were both diseases are reported symptomatic on the same patient, and
      despite its rarity, it is important to be aware of this possible association for
      the diagnostic, therapeutic and prognostic implications it has.

PMID- 14963854
TI  - [Expansile cyst, twin formation and possible parasagittal cerebral injury].
AB  - INTRODUCTION: Prenatal intracranial anomalies of a cystic nature are mainly
      either malformations (arachnoid cysts) or disruptive (porencephaly). They are
      usually incidental findings and, unless they undergo a progressive increase in
      size and become expansile or offer clinical features, they are usually managed
      'expectantly'. Disruptive defects are more frequent in twin pregnancies. CASE
      REPORT: A one and a half-month-old male patient, fruit of a bichorial twin
      pregnancy, with bouts of paleness, cyanosis around the mouth and movements of the
      mouth that initially responded to treatment with valproate. Physical exploration
      was normal except for a significant increase in the cephalic perimeter. A notable
      anaemia was observed and neuroimaging revealed a left temporal
      intraparenchymatous cystic lesion; in addition, magnetic resonance imaging showed
      alterations in the linear and symmetrical signals in the parasagittal region. At
      three months the seizures reappeared and the cyst had increased in size, which
      led to the implantation of a cyst peritoneal shunt. The seizures ceased and the
      size of the cyst became stable, without full re expansion of the brain tissue.
      DISCUSSION: It is necessary to carry out a differential diagnosis of an arachnoid
      cyst and porencephaly. Given the history of being a twin, the notable degree of
      anaemia at the age of one month and the image suggesting parasagittal cerebral
      injury (a pattern of hypoxic ischemic encephalopathy in the full term neonate),
      we think that our patient was suffering from antenatal or perinatal
      cerebrovascular damage, which conditioned the development of an expansile
      porencephalic cyst and cortical damage that accounted for the symptoms of
      epilepsy.

PMID- 14963855
TI  - [Central modulation of a sensory system by a motor command. One intention with
      two results].
AB  - INTRODUCTION AND DEVELOPMENT: Neuronal mechanisms that underlie diverse sensory
      motor integration processes (SMI) are essential for the motor control and
      determine the general organization of the nervous system. Spinal cord, sensory
      relay nucleus of brainstem and thalamus as well as higher motor control
      structures are some of the levels, of increasing complexity, at which several
      processes of SMI occurs during the execution of a motor act. The mechanisms that
      underlie SMI strategies operating at higher hierarchical levels of motor control
      are poorly understood. Escape response in teleosts fish is an advantageous
      experimental model for the analysis of the neural basis of behavior and of the
      mechanisms and functional consequences of diverse strategies of ISM. We describe
      several levels of ISM that operate in the neural system that organize this
      response in most teleosts and we deal with a detailed description of a novel
      strategy that occurs in Gymnotus carapo, a South American weakly electric fish.
      In this species, the activation of the Mauthner cell, a command neuron for the
      initial phase of escape, produces a powerful modulation of the sensory system
      responsible for active electrorreception, its main sensory modality. CONCLUSION:
      The neural basis of behavior, even those relatively simple, exhibit several
      strategies of complex SMI that determine its performance and whose cellular
      mechanisms begin to be unraveled.

PMID- 14963856
TI  - [A reversible posterior leukoencephalopathy syndrome].
AB  - INTRODUCTION AND METHOD: The reversible posterior leukoencephalopathy (RPLS) was
      initially described by Hinchey et al in patients hospitalized due to different
      acute process that cause hypertension and renal disease that were being treated
      with immunosuppressive agents. Clinically it produces an acute or subacute
      encephalopathy that usually agrees with a fast increase of blood pressure.
      Neuroimaging technique demonstrated abnormalities involving the white matter,
      especially bilateral edema in the posterior portions of the cerebral hemispheres,
      although it can also affect to any other cerebral area, trunk or cerebellum. The
      production mechanism is not well know. In case of hypertensive encephalopathy and
      eclampsia of pregnancy it is believed to be caused by vascular and endothelial
      autoregulation alterations, and when it's related to immunosuppressors the edema
      seems to have a cytotoxical origin. The particularity that defines the RPLS is
      that, in most cases, neurological symptoms and white matter lesions disappear
      after anti hypertensive treatment or when immunosuppressive agents is ceased.
      CONCLUSION: The RPLS is an uncommon neurological complication, however each time
      more news cases appear in the medical literature. The excellent evolution and
      treatment response that these patients show and the full clinical and
      radiological recuperation suggest the need of its early identification to avoid
      unnecessary diagnostic studies or wrong treatments.

PMID- 14963857
TI  - [Brain metastasis and the carcinoembryonic antigen].
AB  - INTRODUCTION: Neurological complications have a notable repercussion on the
      quality of life of patients with systemic cancer, and can even become the direct
      cause of death. The complication that causes most concern is undoubtedly brain
      metastasis, because of its difficult management and because there has been an
      upward tendency in its incidence in the last few years. AIMS: The aim of this
      study is to provide a review of the literature about brain metastases and, more
      particularly, about the carcinoembryonic antigen (CEA) as a marker of these
      pathologies. DEVELOPMENT: In general it is reckoned that 60% of all brain
      metastases start from the lung and most of them are multiple when they are
      diagnosed, which suggests a possibly mistaken staging of these patients. The
      carcinoembryonic antigen is the prototypical tumour marker, and it is usually
      found in higher concentrations in the cerebrospinal fluid of patients with
      metastatic tumours in the central nervous system. As the CEA goes through the
      blood brain barrier, it behaves in a similar way to IgA due to their having
      homologous molecular weights. This allows us to employ the same hyperbolic
      distribution curve that is used as a reference for lgA to distinguish between
      intrathecally synthesized CEA and that which diffuses from the systemic
      circulation. CONCLUSIONS: In spite of the progress that has been obtained with
      the new therapies, brain metastases continue to have a poor prognosis. Hence,
      there is a need to identify new tumour markers that allow a diagnosis to be
      established before the clinical methods and presentations.

PMID- 14963858
TI  - [Instruments for evaluating behavioural disorders].
AB  - AIMS: This review considers, from a theoretical clinical point of view, several
      interview based instruments used in the areas of neuropsychology, psychology and
      psychiatry that have been designed to evaluate the associated symptoms in several
      diagnostic categories or types in the different editions of the Diagnostic and
      statistical manual of mental disorders. DEVELOPMENT: The study of
      psychopathology, especially in children and adolescents, has one prior requisite:
      a thorough knowledge of how categorical disorders are organised by axes and the
      reason for the groups of symptoms and their variations located in each criterion.
      Consequently, in order to perform a diagnosis in child psychopathology, different
      criteria have to be fulfilled, according to the presence of the different
      disorders associated with a particular pathology, and the different evaluation
      tools provide a multiple approach that allows the behavioural problems to be
      evaluated. CONCLUSIONS: We currently have a series of diagnostic instruments
      available that are recommended for individual clinical study and can be applied
      both by parents and by teachers. The need then arises to research into whether
      the symptoms reported by parents and teachers have similar characteristics or
      whether, to the contrary, there are differences in the behaviour observed in
      distinct contexts, which would require a further analysis of the contextual
      particularities the patient moves in.

PMID- 14963859
TI  - [Neuropsychological deficits in alcoholics: some implications for road safety].
AB  - AIM: There are various published studies showing that chronic alcoholics present
      cognitive deficit. In this conference we would like to review the most actual
      studies focusing on the neuropsychological alterations as consequences of the
      long and abusive alcohol intake. We also will analyse the involvement of these
      deficit in a complex task as driving. DEVELOPMENT: The long and abusive alcohol
      intake produces an affectation of the central nervous system. We could observe
      its consequences both in short and long term. Attention and memory deficit and a
      slowness of information processing are very common. However, complete
      neuropsychological assessment and rehabilitation programs are convenient. This is
      an important topic if we consider the high number of traffic accidents in which
      alcohol intake is one of the possible causes. Therefore, it is necessary to pay
      attention to the persons working daily with a car, such as taxi or bus drivers,
      especially those of them who are alcoholics in abstinence, chronic alcoholics and
      people who suffer from alcohol abuse. CONCLUSION: The control of this situation
      and the publicity about neuropsychological sequels of alcoholism could contribute
      in an efficient way towards safety in road.

PMID- 14963860
TI  - [Memory evaluation using functional magnetic resonance: applications in
      preoperative patients and in Alzheimer s disease].
AB  - The assessment of memory functions related to medial temporal lobe has become one
      of the most important issues on current neuropsychology. On this communication,
      we review the results which our research group has achieved using two functional
      magnetic resonance Image procedures to assess memory function:  Hometown walking 
      task and an  encoding/retrieval  task using complex images. Nine patients with
      tumoural temporal lesions performed the hometown walking task. The results of
      these patients showed either a bilateral or contralesional representation of
      memory function. These results confirm those obtained by Jokeit, Okujava y
      Woermann (2001), and they seem to prove that this protocol is useful to determine
      the preservation of memory function in the non damaged hemisphere. On the other
      hand, the images encoding/retrieval task has been run by two groups of four
      patients diagnosed as Alzheimer disease and mild cognitive impairment, and
      another group of five patients who participated as a control group. According to
      our hypothesis, the results have shown a lower activation at the left
      parahippocampal gyrus in mild cognitive impairment and Alzheimer disease patients
      than controls, just as a lower bilateral activation in the same structure for the
      Alzheimer group than the control group. As a whole, our results show how
      important may become functional magnetic resonance image for neuropsychological
      assessment of memory, and as a diagnostic tool for CNS diseases.

PMID- 14963862
TI  - [Transaminase disorders in asphyxiated term infants: a good neurological
      marker?].

PMID- 14963864
TI  - Is help really on the way?

PMID- 14963865
TI  - Transfer of asthma management responsibility from parents to their school-age
      children.
AB  - This study used grounded theory to explore the process of transfer of
      responsibility for asthma management from parents to their school-age children.
      Interviews were conducted with 11 mothers, 2 fathers, 1 grandmother, and their 14
      children who were between 8 and 13 years old. Responses revealed that transfer of
      responsibility within families is a complex, uneven process that occurs over
      years and involves identifiable stages and transitions. The Theoretical Model for
      Parent-Child Transfer of Asthma Responsibility emerged from the data. The central
      concept underlying the process was controlling the situation. Specific cues
      stimulated changes in parent-child responsibility.

PMID- 14963866
TI  - Technological advances in pediatrics: challenges for parents and nurses.
AB  - Ongoing technological advances in pediatrics are improving the survival rates
      among babies born with life-threatening anomalies. For these neonates, surgeries
      like brain shunts, trachea, gut and heart reconstruction, and organ transplants
      are replacing palliative care. Although parents and health care professionals
      alike are celebrating the successes, advancing technology also raises issues for
      everyone involved. This paper incorporates Dunst and Trivette's Effective
      Helpgiving framework and the Calgary Family Intervention Model to recommend
      nursing care that moves beyond life-saving highly technical surgical procedures
      and responds to the challenges parents face with their children with complex
      congenital heart disease, for example, who have "beat the odds."

PMID- 14963867
TI  - One breath at a time: living with cystic fibrosis.
AB  - The purpose of this qualitative investigation was to describe the lived
      experiences of families caring for a child with cystic fibrosis at the time of
      initial diagnosis. Phenomenological research methodology as described by Colaizzi
      (1978) was used to guide the investigation. A purposive sample of 9 family
      members voluntarily participated in the study. Data were gathered through focus
      groups and written narratives. Data analysis yielded 3 essential theme clusters
      with subthemes: Falling Apart, Pulling Together, and Moving Beyond. Within the
      theme of Falling Apart, the subthemes of Devastation of Diagnosis, An All
      Encompassing Sense of Fear and Isolation, and An Overwhelming Sense of Guilt and
      Powerlessness are described. The theme of Pulling Together included the subthemes
      of Perpetual Vigilance and Returning to Normalcy, and the third theme of Moving
      Beyond included the subtheme of An Optimal Unfolding of a New Kind of
      Consciousness. This article describes in detail the themes and subthemes
      identified during data analysis and the fluid nature of the relationship that
      exists within the essential structure of caring for a family member with cystic
      fibrosis. The diagnosis of cystic fibrosis most often comes as a life-shattering
      experience to families. Lifestyle readjustments are made in an attempt to return
      to some sense of family normalcy. In order to achieve stability in their daily
      lives, families are vigilant in the care and monitoring of the health of a child
      with cystic fibrosis. Ongoing support from health care professionals that is
      grounded in the realities of living with cystic fibrosis is critical. This study
      describes how families develop their own unique way of controlling the experience
      of living with cystic fibrosis, one day and one breath at a time.

PMID- 14963868
TI  - The use of EMLA cream to decrease venipuncture pain in children.
AB  - Venipuncture is one of the most painful medical procedures for a child, and it is
      one of the most frequently performed. This literature synthesis reviews evidence
      for the use of eutectic mixture of local anesthetics (EMLA) cream to reduce the
      pain children experience during venipuncture. EMLA cream was compared with
      placebo, iontophoresis, and amethocaine cream and was found to be an effective
      local anesthetic for pediatric venipuncture pain during both intravenous
      cannulation and phlebotomy.

PMID- 14963869
TI  - Relieving children's pain: nurses' abilities and analgesic administration
      practices.
AB  - A primary purpose of this study was to examine relationships among nurses'
      knowledge and attitudes about children' pain relief, nurses' abilities to
      overcome barriers to optimal pain management, nurses' analgesic practices, and
      pain levels of hospitalized children. Significant positive relationships were
      found between nurses' (N = 67) analgesic administration and children's pain, and
      between nurses' years of practice with children and nurses' abilities to overcome
      barriers to optimal pain management. The children's (N = 132) mean pain level was
      1.63 (scale of 0 to 5), with one half of the children reporting moderate to
      severe pain. Of the 117 children who reported pain, 74% received analgesia.
      Nurses administered a mean of 37.9% of available morphine and means of 36% to 54%
      of recommended amounts of morphine, acetaminophen, and codeine.

PMID- 14963870
TI  - Taking a bite out of policies: a look at the policies affecting our nation's
      dental health.

PMID- 14963871
TI  - Children reading.

PMID- 14963873
TI  - A double concern: grandmothers' experiences when a small grandchild is critically
      ill.
AB  - Grandmothers play an active part in family health and illness, but so far they
      are peripheral in both nursing and nursing research. This article addresses
      grandmothers' lived experiences when a small grandchild is critically ill. A
      convenience sample of 7 grandmothers was interviewed once. With the use of the
      methodology of Van Manen, (1990), the essence of the phenomenon was found to be a
      "double concern," a worry and loving care that encompassed both parents and
      grandchildren. Although the findings have limitations, they constitute a
      systematic and thematic description of Danish grandmothers' experiences and
      therefore add to a family-oriented body of knowledge in pediatric nursing.

PMID- 14963875
TI  - Chlorhexidine versus povidone-iodine for central venous catheter site care in
      children.
AB  - The number of children receiving central venous catheters (CVCs) for the
      administration of medications is at an all-time high. Unfortunately, placement of
      these CVCs is not without risks. Infection of CVC insertion sites is one of the
      most common, yet often preventable, causes of nosocomial bacteremia in both
      children and adults worldwide. Throughout the years, multiple practice
      recommendations have been made regarding the proper site care of CVCs. The most
      popular antimicrobial solution used for site care has traditionally been povidone
      iodine. Chlorhexidine gluconate solution, however, has been shown to be more
      effective than povidone-iodine in preventing CVC-related infections in adults.
      There continues to be controversy regarding the efficacy and safety of
      antimicrobial solutions for pediatric CVC site care. An evidence-based approach
      was used to determine current recommendations for CVC site care in children.

PMID- 14963878
TI  - Predictive validity of the Psychopathy Checklist: Youth Version for general and
      violent recidivism.
AB  - Several authors have expressed concern regarding the use of youth psychopathy
      assessments in determinations of risk for general and violent offending. The
      Psychopathy Checklist: Youth Version (PCL:YV) was completed with 182 male
      adolescent offenders in this prospective study (average 14.5 month follow-up) of
      general and violent recidivism. Both a two-factor and three-factor model of the
      PCL:YV significantly predicted general and violent recidivism at a predictive
      accuracy ranging from 68 to 63%. However, regression analyses indicated these
      associations were explained primarily by behavioral psychopathic symptoms, rather
      than interpersonal or affective traits. Implications for the use of psychopathy
      assessments for risk during adolescence are discussed.

PMID- 14963879
TI  - Psychopathic traits in adolescent offenders: an evaluation of criminal history,
      clinical, and psychosocial correlates.
AB  - Although a large body of research has established the relevance of psychopathy to
      adult offenders, its relevance to adolescent offenders is far less clear. The
      current study evaluated the clinical, psychosocial and criminal correlates of
      psychopathic traits in a sample of 226 male and female incarcerated adolescent
      offenders. According to an 18-item version of the Psychopathy Checklist-Youth
      Version (PCL-YV; Forth, Kosson, & Hare, 2003), only 9.4% exhibited a high level
      of psychopathic traits (PCL-YV>/=25). Consistent with past research, higher PCL
      YV scores were positively associated with self-reported delinquency and
      aggressive behavior and were unrelated to emotional difficulties. Although higher
      PCL-YV scores were associated with the experience of physical abuse, the only
      psychosocial factor to predict PCL-YV scores was a history of non-parental living
      arrangements (e.g. foster care). In terms of criminality, a violent/versatile
      criminal history was positively associated with psychopathic traits. However, PCL
      YV scores were unrelated to participants' official criminal records for total,
      non-violent, violent, and technical violation convictions. In conclusion, the
      data partially support the construct validity of psychopathy with adolescent
      offenders, but some inconsistencies with prior adult and adolescent psychopathy
      research were evident. These issues are discussed.

PMID- 14963880
TI  - Psychopathy scores and violence among juvenile offenders: a multi-measure study.
AB  - This study examined the relations between psychopathy scores and violent behavior
      in 113 incarcerated adolescents. We compared the results of four different
      instruments designed to assess psychopathy features among juveniles-the
      Psychopathy Checklist: Youth Version (PCL:YV), two versions of the Antisocial
      Processes Screening Device (APSD), and a Psychopathy Content scale on the Millon
      Adolescent Clinical Inventory (MACI). We found that PCLY:YV scores were
      significantly correlated with violent offense history, unadjudicated violence,
      and institutional violence, as well as measures of the severity and
      instrumentality of prior violence. Receiver operating characteristic analyses
      generated statistically significant effect sizes (AUC values) ranging from 0.64
      to 0.79. The three other measures generated statistically significant
      correlations with one or more of the violence criteria, although correlations and
      effect sizes tended to be smaller in magnitude. Our results offer some support
      for the validity of these measures of psychopathic features, and the value of the
      PCL:YV in particular, with respect to short-term measures of violence outcome
      among juvenile offenders.

PMID- 14963881
TI  - Validity and structure of a self-report measure of youth psychopathy.
AB  - An interest in early identification of youth who may be at risk of psychopathy
      has generated measures for age-appropriate screening and assessment. This study
      examines the structural, concurrent, and divergent validity of the Psychopathy
      Content Scale, a 20-item self-report instrument derived from the Millon
      Adolescent Clinical Inventory (MACI). Data for 481 youths who had taken the MACI,
      the Child Behavior Checklist Youth Self-Report (YSR), and the Massachusetts Youth
      Screening Instrument, Second Version (MAYSI-2), were analyzed. Results showed
      that the PCS is best described by a two-factor model and that analyses of the two
      factors offer limited support for convergent and divergent validity. High scores
      on both factors were associated with high YSR and MAYSI-2 scales, suggesting that
      the measure identified youth who were distressed on several measures of
      emotional, psychological, and behavioral disorder.

PMID- 14963882
TI  - The relationship between psychopathic features, violence and treatment outcome:
      the comparison of three youth measures of psychopathic features.
AB  - Few studies have compared self-report and clinician-administered measures of
      youth psychopathic features in juvenile-justice settings in terms of antisocial
      behavior and treatment indices. In a sample of 85 adjudicated delinquents, the
      predictive validities of the Antisocial Process Screening Device (APSD), the
      modified Childhood Psychopathy Scale (mCPS), and the Hare Psychopathy Checklist:
      Youth Version (PCL:YV) were tested. Three indices of institutional antisocial
      behavior (physical aggression; verbal aggression; administrative infractions) and
      two indices of treatment progress (time to treatment level promotion; whether
      treatment levels were dropped) were used as external correlates. The self-report
      measures (mCPS more so than APSD) were more consistently and strongly related to
      antisocial behavior and to the days required to progress in treatment than the
      PCL:YV. The following issues are discussed: (i) implications of the potential
      impact of measurement format on the understanding and predictive validity of
      youth psychopathy features and measures; (ii) the differential predictive
      validity of self-report versus clinician-administered measures; and (iii) the
      potential practical utility of measures of psychopathic features in youth.

PMID- 14963883
TI  - Psychopathic-like traits in childhood: conceptual and measurement concerns.
AB  - Can psychopathy be identified in pre-adolescent children? This question has both
      theoretical and practical implications. So far, attempts to answer this question
      have been made by making downward extensions of symptoms of the disorder as found
      in adults. We argue that for the construct of psychopathy to be viable as a
      construct in childhood it is necessary to demonstrate that a coherent syndrome of
      symptoms can be identified during childhood. To achieve this it is necessary
      first to use a strong measurement model, and second to use developmentally
      informed conceptualizations of key constructs. In order to progress from the
      measurement perspective, it is necessary to demonstrate (i) configural invariance
      of symptoms across key ages, (ii) similar performance of age cognate symptoms
      across key ages, and (iii) stability of relative standing on the latent trait
      across age. Novel techniques including item response methods and structural
      equation modelling techniques are required. In this paper, we review the relevant
      literature and evaluate the strength, or otherwise, of the evidence that key
      traits of psychopathy can be observed in childhood.

PMID- 14963884
TI  - Assessing risk for violence among male and female civil psychiatric patients: the
      HCR-20, PCL:SV, and VSC.
AB  - This study evaluated the predictive validity of violence risk assessments
      conducted using the HCR-20, the Psychopathy Checklist: Screening Version
      (PCL:SV), and by the Violence Screening Checklist (VSC) in a sample of 268
      involuntarily hospitalized male and female psychiatric patients. Information
      pertaining to violence and crime was coded from medical charts and correctional
      records. The HCR-20/PCL:SV evidenced modest non-significant associations in
      postdictive assessments of inpatient violence among men. Moderate to strong
      significant associations were found between the HCR-20/PCL:SV and inpatient
      violence among women. Pseudo-prospective assessments using the HCR-20 and PCL:SV
      resulted in moderate to large relationships with violence and crime in men and
      women following community discharge. It is concluded that the VSC is a promising
      tool for assessing acute inpatient violence risk with men. Findings offer
      preliminary validation of the predictive validity of the HCR-20 and PCL:SV with
      female civil psychiatric patients.

PMID- 14963885
TI  - The New Orleans Forensic Aftercare Clinic: a seven year review of hospital
      discharged and jail diverted clients.
AB  - This paper provides a review of the Forensic Aftercare Clinic Conditional Release
      Program (FAC), which has been operating since December, 1995, in New Orleans, LA.
      The FAC is a community based program that provides clinical, rehabilitative, and
      supervisory services to individuals who have been found not guilty by reason of
      insanity or unrestorably incompetent to proceed and who have been discharged from
      inpatient settings or diverted from jail settings and placed on conditional
      release by district court orders. 119 clients participated in FAC over a 7 year
      period. Forty-one (34.4%) had their conditional release revoked. Of the total
      population, 12 (10.1%) were re-arrested on at least one charge, 3 (2.4%) were
      arrested on felony charges, and 9 (7.6%) on misdemeanors. Only two of these
      charges were violent, resulting in no significant harm to victims. Twenty (16.8%)
      were hospitalized at least once due to relapse. Clients diverted from jail to
      community settings did not differ significantly on most variables from clients
      who were discharged from long-term hospitalization. Data related to public safety
      and client diversion demonstrate that clients, when appropriate, can be safely
      diverted to the community in lieu of hospitalization. The number of statewide
      clients who have been discharged from the forensic hospital into the community
      has increased steadily from 13 in 1995 to 29 in 2002, and statewide diversion
      clients have steadily increased from 0 in 1992 to 20 in 2002. The increase in
      statewide diversion clients and forensic discharges over this 7 year period
      indicates that stakeholders see the viability of the program as an alternative to
      as well as a step-down from long-term forensic hospitalization.

PMID- 14963886
TI  - The economics of hospital reform: from hierarchical to market-based incentives.
AB  - Heavy investment over the past 30 years has made the hospital sector the largest
      expenditure category of the health system in most developed and developing
      countries. Despite shifts in attention and emphasis toward primary care as a
      first point of contact for patients, in most countries, hospitals remain a
      critical link to health care, providing both advanced and basic care for the
      population. Often, they are the provider "of last resort" for the poor and
      critically ill. Although, it is clear that hospitals play a critical role in
      ensuring delivery of health services there is much less agreement about how to
      improve the efficiency and quality of care provided. This article reviews recent
      hospital reforms undertaken throughout the world, with an emphasis on
      organizational changes such as increased management autonomy (often referred to
      as autonomization) and corporatization. It provides some insights about these
      popular reform modalities from a review of the literature, reform experiences in
      other sectors and empirical evidence from hospital sector itself. The material
      presented tries to answer three questions: (a) what problems did this type of
      reform try to address; (b) what are the core elements of their design,
      implementation and evaluation; and, (c) is there any evidence that this type of
      reform is successful in addressing problems for which they were intended? While
      this paper focuses on issues related to the design of the reforms, the paper also
      reports the findings from a larger study that examined the implementation and
      evaluation of such reforms so that they will be available to countries that are
      considering venturing down this reform path.

PMID- 14963887
TI  - Social capital, gold for telemedicine?
AB  - Value norms within an interactive social network, social capital, can improve
      many aspects of the quality of life including health. Effective means of
      communication are key to making the social capital available. Telemedicine is
      therefore well placed to playing an important role in providing social capital to
      many groups in a society, which are at present deprived of this resource for
      maintaining health.

PMID- 14963888
TI  - Shortage of human resources in the Hungarian health care system: short-term or
      long-term problem?
AB  - The Quality-management Committee of the Hungarian Hospital Federation and the
      Semmelweis University Health Services Management Training Centre, recognizing the
      threats of the human resources shortage and the consequential quality problems in
      the delivery of health care services, have launched a program for identifying the
      major problems and developing recommendations for decision makers and health
      service managers. The identification of the problems was performed by a task
      force group using a systematic methodology, recommendations were based on these
      findings. Members of the task force group were delegated by the Hungarian
      Hospital Federation and the Health Services Management Training Centre.
      Additional members were invited from the Ministry of Health and various other
      professional organizations.

PMID- 14963889
TI  - [Cooperation between Chili and France in management training in the Chilean
      public health sector].
AB  - A cooperation programme launched in 1999 by the Chilean Health Department and the
      French National College of Public Health (ENSP France) has now been running for
      four years. Its aim was to create and validate a national scheme for manager and
      executive training within the Chilean public hospital systems. Developed in
      partnership with the Public Health National College of Rio de Janeiro (Fondation
      Oswaldo Cruz) with whom ENSP France has teamed up for 10 years, this cooperation
      was designed by the Chilean partner as a contribution to the definition and
      implementation of a national policy on Human Resources which might follow the
      vast reform of the health system currently underway in the country. The scheme
      which gained international support is backed by a network of 5 universities (7 in
      2004) associated with the Chilean Health Department, in a joint national
      development project for in-house management training for the management teams
      already in office. More than 100 manager and senior executives et 150
      intermediate executives were thus trained between 2000 and 2003. The present
      scheme est presently being modified to meet new challenges arising from the need
      to support important changes occurring in the management of Chilean public
      hospitals, to give them more independence, while encouraging a network of all
      carers. The ENSP input concerns a line of transfer of competence in training and
      teaching engineering for all the Chilean partners involved. A module on know-how
      development support in 'remote control' open training engineering was added in
      2002, resulting in the French ENSP concluding a collaboration agreement with the
      Universite de Technologie de Compiegne (France). Moreover, support for
      implementing an accreditation scheme for management training for the Chilean
      health sector is under way, linking both French and Brazilian ENSP. Designed from
      the start on a regional South Cone/Brazil basis, a new expansion phase will be
      added to this international programme in 2004 (as regards principles and methods)
      through a Chilean/French cooperation towards Paraguay.

PMID- 14963890
TI  - Country case report Uganda.
AB  - Health status indicators for Uganda are poor partly because of the repercussions
      of the historical conflicts. Poverty among the population is high. According to
      the Burden of Disease study done in 1995, over 75% of the life years lost due to
      premature death were due to ten preventable diseases. Government of Uganda, in
      collaboration with the Development Partners, has evolved a number of strategies
      to address priority concerns in the Health Sector. In 1999 a 10-year National
      Health Policy (NHP) was adopted together with the development of a five year
      Health Sector Strategic Plan (HSSP) to guide the implementation of the NHP. The
      NHP and the HSSP guide the current structure of the health services in the
      country, including the hospital services. However the focus in the reform process
      has been on primary health care but the hospitals have not been given sufficient
      attention. This country report concludes that the resources available for the
      health services in the country are very limited and the biggest challenge is to
      get the most out of these scanty resources. A further challenge identified is the
      need also to bring the hospitals in the mainstreamed health reform process. There
      is need for the hospitals to re-orientate themselves and strengthen the promotive
      and preventive services in addition to curative, rehabilitative and palliatives
      services. Finally, there is the need to improve access to hospital services as
      well as the standard of the hospital service.

PMID- 14963891
TI  - How many years can hospital master plans be effective.
AB  - This paper considers the effectiveness of master planning for hospitals based on
      recent surveys carried out in the UK and Japan. In the UK, Northwick Park
      Hospital, built in the 1970s, was selected for surveys in 1999 and 2002 because
      of being a typical example representing John Weeks' 1960s concept of
      'indeterminate architecture' to cope with growth and change. In Japan, the Chiba
      Cancer Center, also built in the 1970s, was selected to survey in 2002 because of
      being a good example of a 'multi-wing type' configuration developed in Japan for
      growth and change. The paper concludes with the determination that the master
      plans for both these hospitals have been generally successful, despite the fact
      that changes were often not anticipated by the architectural proposals. In
      addition, it is seen that a master plan can be effective for at least a period of
      30 years given certain conditions.

PMID- 14963892
TI  - Development of guidelines for design and construction of hospitals and health
      care facilities.
AB  - The Guidelines for Design and Construction of Hospitals and Health Care
      Facilities is the most widely referred to design document in the USA and is
      influential throughout the world. The Facility Guidelines Institute (FGI) was
      founded to provide continuity in the guidelines revision process. FGI functions
      as a contractual, fundraising, and coordinating entity to develop and enhance the
      content and format of guidelines publications and of ancillary services that
      encourage and improve their application and use. The Guidelines and the
      methodology for revising them have been, and still are, in an evolutionary
      process. It is the desire of the AIA/AAH and FGI to see that the process
      continues to change and improve with each passing cycle.

PMID- 14963893
TI  - Health sector reforms--what about hospitals?
AB  - Health is a changing concept. There are cultural, social, economic and technical
      aspects involved in this concept. Out of the eight Millennium Development Goals
      adopted by the UN in 2002, three goals in particular address health issues. But
      all the goals have a strong bearing on health--be it poverty and hunger
      eradication, education, gender equality and women empowerment, the physical
      environment or social and economic development. Health care must be complete and
      offer specialist and hospital services as well. Hospital services must be related
      to the major outcomes desired by its users. Hospital service provision must also
      be connected to current needs and not based on history or physical
      infrastructure. The roles of hospitals as specialist service providers are today
      widely acknowledged. They, however, do not just provide health care, but also
      training for staff in different skills, generating trained nurses, laboratory
      technicians and other health professionals. Against this background, how then can
      a hospital, which plays a number of necessary, highly desired or sometimes
      unavoidable roles, be best defined--besides the buildings themselves?

PMID- 14963894
TI  - [A 40-year cohort study on cancer mortality among female workers with manual
      spinning of chrysotile asbestos].
AB  - The mortality of malignant tumors among female workers with manual spinning of
      chrysotile alone was investigated by a retrospective cohort study and was
      calculated based on the person-year at risk of the observed group by the life
      table method. The standardized mortality ratio (SMR), the relative risk (RR),
      attributive risk (AR) and their corresponding 95% confidence intervals (CIs) were
      calculated based on the mean age-specific mortality rate of local female
      population. 5,681 female workers with manual spinning of chrysotile for at least
      one year between 1960 and 1980 were traced to the end of the year of 2000. A
      total number of 858 death cases by all causes were found. The results showed that
      the percentage of specific causes of death, cancer (24.83%) was the first cause
      of death, and the lung cancer (40.85%) was the most prevalent. SMRs for all
      cancers (1.35) and for lung cancer (3.88) were significantly elevated than those
      of the control group. The results indicated that the excess of lung cancer among
      female workers with manual spinning of chrysotile did not likely to be dependent
      on the amphibole hypothesis, the hypothesis of mineral oils exposure and
      cigarette smoking, but was likely related to manual spinning of asbestos
      operation produced airborne fibers that were generally longer than 10 microns in
      length than other operations using chrysotile.

PMID- 14963895
TI  - [Study on association of polymorphism of MGP(T-138C) gene and blood lead level in
      children].
AB  - In order to explore the relationship between polymorphism of matrix gamma
      carboxyglutamic acid protein (MGP) gene and blood lead level in children and to
      screen the gene which associated with lead poisoning, three hundreds and fifty
      five children aged at 6 to 12 years old living in lead pollution area were
      recruited in this study. The blood lead level were measured. The T-138C
      polymorphism of MGP gene was analyzed with the method of polymerase chain
      reaction-restriction fragment length polymorphism(PCR-RFLP). The blood lead level
      in children with wild type homozygotes(TT) was higher than those with mutated
      homozygotes(CC) (468.24 micrograms/L. vs. 430.31 micrograms/L, P < 0.05). The
      results indicated that the T-138C polymorphism of MGP gene in promoter region
      influenced blood lead level in children lived in lead pollution area.

PMID- 14963896
TI  - [Effect evaluation of three cell culture models].
AB  - Primary rat hepatocytes were cultured using three kinds of models in vitro and
      the enzyme leakage, albumin secretion, and cytochrome P450 1A (CYP 1A) activity
      were observed. The results showed that the level of LDH in the medium decreased
      over time in the period of culture. However, on 5 days, LDH showed a significant
      increase in monolayer culture (MC) while after 8 days LDH was not detected in
      sandwich culture (SC). The levels of AST and ALT in the medium did not change
      significantly over the investigated time. The basic CYP 1A activity gradually
      decreased with time in MC and SC. The decline of CYP 1A in rat hepatocytes was
      faster in MC than that in SC. This effect was partially reversed by using
      cytochrome P450 (CYP450) inducers such as omeprazol and 3-methylcholanthrene (3
      MC) and the CYP 1A induction was always higher in MC than that in SC. Basic CYP
      1A activity in bioreactor was keeped over 2 weeks and the highest albumin
      production was observed in bioreactor, and next were SC and MC. In conclusion,
      our results clearly indicated that there have some advantages and disadvantages
      in each of models in which can address different questions in metabolism of
      toxicants and drugs.

PMID- 14963897
TI  - [Study on distribution of endemic arsenism in China].
AB  - Drinking water and burning coal endemic arsenism as a severe disease is confirmed
      by National Ministry of Health in China in 1992. It is not uniform survey of the
      disease for the whole country from its report in 1980 in xijiang. Therefore
      National Ministry of Scientific and Technology in China supports to study on
      distribution of endemic arsenism in 21 provinces in China, so that it can know
      the basic distribution of endemic arsenism in China, and the data results will be
      a guide for the disease prevention and control. The project used environmental
      epidemiology study including retrospective epidemiology, present situation survey
      of the disease in severe areas and sampling investigation in unknown areas,
      collecting data of exposure population and arsenism cases. At the same time, the
      data of arsenic level in environment were collected, and environment samples were
      analyzed by standard chemical method. The both data were statistical analysis by
      access database and SAS procedure in computer. Through the study, it achieves the
      expected aim that grasps spreading distribution of drinking water arsenism and
      burning coal arsenism, including arsenic level in water, coal, food and air, as
      well as patient's condition of the disease at macroscopic. Drinking water endemic
      arsenism distributed in 8 provinces, 40 counties, affecting 2,343,238 peoples,
      among 522566 peoples expositing to the drinking water arsenic higher than 0.05
      mg/L, and 7821 arsenism patients were diagnosed. Burning coal endemic arsenism
      spreads in 2 provinces, 8 counties, affecting 333905 peoples, 48438 peoples
      exposing to high arsenic of burning coal pollution, and 2402 peoples causing
      chronic arsenic poising by coal burning. Drinking water endemic arsenism: Nemeng,
      Shanxi is a severe drinking water endemic region also. Wusu city in Xinjiang is
      old arsenism area, which reformed drinking water to decrease arsenic, so chronic
      arsenic poisoning condition decreasing. Reforming drinking water measures to
      decreees arsenic were performed in some areas of Neimeng and Shanxi. On other
      hand, 1 county of Jilin and 1 county of Ningxia as drinking water arsenism areas
      were affirmed. 11 counties of Shanyi, 1 Banner of Nemeng, 1 city of Jilin, 1
      county of Qinhai and 1 counties of Anhui province were discovered for new
      drinking water arsenism areas in this survey. Shunyi district of Beijing has high
      arsenic in drinking water. Otherwise, high arsenic content in drinking water in
      some areas decreased to lower than 0.05 mg/L, which including some villages of
      Liaoning province, Tongxing city of Zhejiang province, and Tianzhu village of
      Shunyi district in Beijing. Blackfoot disease related to high arsenic in drinking
      water in Taiwan province does not include in this study. Burning coal endemic
      arsenism: Guizhou province has a typical burning coal arsenism areas in China and
      world. Although to reform stove and decreasing arsenic pollution, but the chronic
      arsenic poisoning from domestic coal combustion exists, because it located high
      seal level and poor areas. Some new burning coal arsenism areas in Shanxi
      province were found, which produced air pollution and food pollution of arsenic
      from domestic coal combustion for cooking and heating. The paper summarizes the
      arsenic distribution levels in drinking water and in environment of burning coal.
      At the same time, preventive and control measures of endemic arsenism were
      provided.

PMID- 14963898
TI  - [Study on the estrogenic effect of the organic extracts from tap water and source
      water].
AB  - In order to study the estrogenic effects of the organic extracts from tap water
      and source water, two in vitro assay and one in vivo short-term assay were
      performed to detect the estrogen-like activity of the component of water. The
      results showed that at the concentration of 50 ml relevant to real water, the
      recombinant yeast assay and MCF-7 cell proliferation assay could both detected
      the estrogen-like activity and with increase of concentration, the component
      exhibited an increasing estrogenic effects. The dose inducing the maximum effect
      in cell proliferation assay was 250 ml and in recombinant yeast assay was 1250
      ml. Exceed this dose with increasing concentration, the estrogenic effects of
      component decreased both in two assay. In uterrtropic assay, doses of 10 L/kg and
      50 L/kg increased the weight of uterus of 18 day ICR female mice significantly.
      All above findings indicated that organic extracts from source water exhibited
      the estrogenic effects. The series of 3 bioassay process displayed sensitivity
      and practicability.

PMID- 14963899
TI  - [Effects of formaldehyde on germ cells of male mice].
AB  - General toxicity and genetic materials damage of formaldehyde on germ cells in
      different stages was studied. In order to discover the toxicity mechanism of
      formaldehyde on germ cells and the biomarkers of effect after the presence of
      damage in germ cells and the estimation index, the relationships between the
      damage of germ cells and the MDA, SDH activity and Cu and Zn. in testicle tissue
      were investigated. Male mice exposed to formaldehyde by i.p. for 5 days.
      Formaldehyde doses were: 0.20 mg/kg, 2.00 mg/kg, 20.00 mg/kg. Mice were killed at
      the 6th day and the 14th day. HE staining was used to study the pathological
      changes happened in testicle tissue. In order to study the changes in sperm, the
      sperms and the abnormality of the sperm's heads were observed. In order to study
      the damage of the genetic material in the germ cells, the frequencies of sister
      chromosome exchanges and the frequencies of MN cells were studied. MDA was
      measured by MDA diagnosis box. Copper and zinc were determined by FAAS. US was
      used to determine the SDH activity in serum and testicle tissue. The results
      showed that: The main pathological changes in testicle tissue of formaldehyde
      groups were degeneration; The sperm quantity was decreased and the sperm heads
      deformation ratio was increased in all formaldehyde groups; There were a
      significant increase of MN ratio in early spermatogenic cells and SCE ratio in
      medial and high dose groups; The MDA in testicle tissue significant increased in
      high dose group. The SDH activity in testicle tissue was declined in all
      formaldehyde groups; There were a significant decline of copper and zinc in
      testicle tissue in high dose group. It is suggested that: Formaldehyde could
      induce genetic materials in spermatogone, primary spermatocyte and caused
      degeneration and necrosis in secondary spermatocyte, spermatogenic cell, sperm;
      The damage of LPO, decline of copper and zinc and SDH activity in mice's testicle
      tissue could be caused by formaldehyde; The effect of lipid peroxidation may be
      one of the toxicity mechanisms of formaldehyde on genetic materials; SDH is the
      biomarkers of effect after the toxicity effects induced by formaldehyde on germ
      cells appeared; Testing the sperm heads deformation ratio is the estimation index
      that can be used to judge the general toxicity of germ cells and the damage on
      their genetic materials of formaldehyde.

PMID- 14963900
TI  - [Fine particles pollution and its impact on the expression of inflammation
      cytokine IL-6].
AB  - To investigate fine particles (PM2.5) pollution and its impact on the expression
      of inflammation cytokine IL-6. Two cities, namely Taiyuan and Beijing, were
      selected to represent two different types of air pollution. Classification air
      sampler was used for PM2.5 collection in the air, and weighting method was used
      to analyze PM2.5 mass concentration. B (a) P in PM2.5 was extracted by methyl
      alcohol using ultrasonic method and Pb in PM2.5 was dissolved in nitric acid and
      hydrogen peroxide. Human alveolar epithelial cell line (A549) was used as target
      cell. Concentration of inflammation cytokine IL-6 was measured by an ELISA kit
      and, the mRNA expression of IL-6 was measured by RT-PCR while A549 cells were
      incubated with PM2.5 in different doses. Air Quality Standard for PM2.5 of U S
      EPA was applied as the reference. The percentage and multiple of exceeding
      standard of PM2.5 concentration of Taiyuan winter, Beijing winter and Beijing
      spring were 100%, 4.23; 90.6%, 2.62; 97.4%, 2.53 respectively. B(a) P in Taiyuan
      winter and Beijing winter were 5.86, 1.09 micrograms/100 m3) respectively that
      was over the standard. Pb level of particle matter in two cities was under the
      Air Guality Standard of Residential Area in China. It was showed an increase of
      protein concentration and mRNA expression of IL-6 in A549 cultured with PM2.5
      compared with untreated cells, presenting a dose-effect relationship. It is
      suggested that PM2.5 pollution was relatively heavy in the study areas and showed
      inflammation damage toxicity.

PMID- 14963901
TI  - [Study on the defluoridation of drinking water with model-La cation exchange
      resin].
AB  - Model-La cation exchange resin was transformed from strong acid cation exchange
      resin, which was used for the defluoridation of drinking water. The 001 x 7
      strong acid cation exchange resin was transformed into model-La cation exchange
      by soaking in the La(NO3)3 solution. The F- in the water was removed by model-La
      cation exchange resin under the optimum condition because it was combined into
      fluoride with the La3+ in the model-La cation exchange resin. The used resin was
      regenerated with the La(NO3)3 solution and was used to defluoridate many times.
      The optimum conditions of transform and defluoridation and regeneration were
      d(rasin) = 0.315-0.600 mm, V(rasin):V(regeneration) = 1:6, t(transform) = 48 h, T
      = 298.16 K(25 degrees C). The defluoridation capacity was 5.60 mg/g in column
      test, and 4.08 mg/g in batch test. The model-La cation exchange resin could be
      used for defluoridation for 8 times. The results suggest that the model-La cation
      exchange resin is a novel material of defluoridation. This method is easy to
      master and the pH value of the solution doesn't need to be regenerated that the
      cost of defluoridation can be reduced significantly and it can be used for a long
      time.

PMID- 14963902
TI  - [Study on monitoring index of individual exposure dose of volatile organic
      compounds in environment].
AB  - In order to study the monitoring index of individual exposure dose of volatile
      organic compounds (VOCs) in environment, the thermal desorption capillary gas
      chromatographic (TD-GC) analysis was used to examine the VOCs level in air and
      the expired breath of female workers. Headspace solid phase micro-extraction gas
      chromatography (SPME-GC) was applied to determine the blood concentration of VOCs
      in female workers. The results from epidemiological study showed clearly that
      concentration of 10 subtypes of VOCs in blood, environmental air and expired
      breath from exposure group were higher than those from control group. The
      findings from the study suggested that the blood concentration of VOCs was
      sensitive and specific and this index might be one of good indexes in assessment
      of individual exposure dose of VOCs.

PMID- 14963903
TI  - [Methodology on the burden of smear-positive pulmonary tuberculosis and the
      communicability of the disease].
AB  - The burden of patients with smear-positive pulmonary tuberculosis(TB) and that of
      the communicability of the disease was investigated by using disability-adjusted
      life year(DALY) as an indicator. An assumed cohort of 2000 cases based on the age
      specific incidence of 794 newly registered smear-positive cases in Beijing in
      1994 was set up. The prognostic tree and diagram model of communicability under
      natural history and direct observed treatment short-course startegy(DOTS) were
      established according to the epidemiological evidence. The results showed that
      29.6% of DALYs would be neglected if the burden caused by the communicability
      have not been considered. The results also showed that DOTS might reduce 97.3% of
      potential cases infected, reduce 92.9% of DALY to patient themselves, and reduce
      99.9% of DALYs caused by the communicability as well.

PMID- 14963904
TI  - [Case-control analysis and follow-up study on risk factors of suicide attempt in
      a rural population in Shandong Province].
AB  - In order to prevent suicide behavior and propose a comprehensive strategy for
      suicide prevention, a cases-control study and then follow-up study in a rural
      population were conducted. The data were analyzed by Logistic model so as to look
      for the risk factors of suicide attempts. The results showed that suicide
      attempts were significantly positive associated with recent stress in life
      events, mental illness, higher scores for lifetime aggression and impulsivity
      while suicide attempts were negative associated with higher scores for the
      quality of life and higher scores for the family cohesion. The study suggested:
      (1) the most important risk factors for suicide was recent stressful life events
      followed by the mental illness as the second, (2) the higher scores for lifetime
      impulsivity was one of the independent risk factor for suicide attempts, (3) the
      model of suicide in rural population in our country is different from that in
      western country. It is important to develop strategies of prevention and
      intervention for this population at higher risk.

PMID- 14963905
TI  - [Time-series analysis on the relationship between air pollution and daily
      mortality in Beijing].
AB  - To quantitively evaluate the associations between ambient air pollutant and daily
      mortality of Beijing and to supply the scientific bases for formulating control
      measures. Air pollutants including CO, SO2, NOx, TSP, PM10. time series analysis
      Poisson regression was used to evaluate the relationship between cause-specific
      deaths and air pollutant, considering the potential confounding factors such as
      seasonal and long-term patterns, meteorological factors (air temperature, air
      humidity), as well as adjusting the influence of flu epidemics in winter of 1998.
      The results showed that in single-factor Poisson regression analysis, there is a
      significant positive correlation between the four pollutants and daily mortality
      except for the relationship between TSP and coronary heart disease deaths. In
      multi-factor Poisson regression analysis, when SO2 increase in 100 micrograms/m3,
      respiratory deaths, cardiovascular and cerebro-vascular deaths, coronary heart
      disease deaths and chronic obstructive pulmonary deaths increased by 4.21%,
      3.97%, 10.68%, 19.22% respectively. Meanwhile, each 100 micrograms/m3 increase in
      TSP associated with 3.19% increase in the respiratory deaths and 0.62% increase
      in the cardiovascular and cerebrovascular deaths. It is suggested that air
      pollution is a risk factor for health and an increase of air pollution level
      might lead to a raise in daily mortality.

PMID- 14963906
TI  - Inadequate calcium intake is a significant determinant on generalised osteopenia
      in Hong Kong Chinese adolescents with idiopathic scoliosis.
AB  - Adolescent idiopathic scoliosis (AIS) is a serious 3-dimentional deformity of the
      spine affecting mostly girls. The prevalence rate is 3%-4% in Hong Kong.
      Generalised osteopenia are found in AIS patients. This study attempted to study
      whether low bone mineral density (BMD) is related to calcium intake in AIS. 582
      AIS patients & 206 healthy controls aged 11-16 years were enrolled. Areal BMD
      (aBMD) and volumetric BMD (vBMD) were evaluated by DXA (Norland-XR-36) and pQCT
      (Densiscan-1000) respectively. Calcium and other nutrients intakes were assessed
      by a food-frequency method. The results showed that absolute calcium intake of
      the subjects were low (< 500 mg/d). Mean calcium intake of AIS girls was
      significantly higher than that of controls[(441 +/- 344) mg/d vs. (390 +/- 281)
      mg/d, P = 0.015]. BMD of AIS was significantly lower than that of controls at
      most skeletal sites from age 11-16 years (P < or = 0.05). The percentage
      difference in BMD increased with age between the AIS and control group.
      Furthermore, calcium intake was significantly correlated with BMD at most
      skeletal sites from age 15-16 years. However, this association was not found in
      the controls. Calcium intake was an independent determinant to predict variation
      of BMD after controlling for confounding variables in multivariate analysis. It
      is suggested that absolute calcium intake of AIS was low. BMD at various skeletal
      sites of the AIS was consistently lower than those of controls across different
      adolescent years, and that the correlation between calcium intake and BMD occurs
      only in AIS but not in healthy control girls implying the importance of calcium
      in bone mineral gain among the AIS, and it also reflected an abnormal mechanism
      of calcium homeostasis and bone turnover in AIS. Further calcium interventional
      study is warranted to confirm the effect of calcium on BMD acquisition in AIS.

PMID- 14963907
TI  - [Roles of ERK1/2 MAPK in vitamin E succinate-induced apoptosis in human gastric
      cancer SGC-7901 cells].
AB  - In order to investigate the roles of ERK1/2 mitogen-activated protein kinase in
      vitamin E succinate (VES)-induced apoptosis in human gastric cancer SGC-7901
      cells, apoptosis was observed by DAPI staining and the phosphorylation of ERK1/2
      by VES at different doses and different time points was measured by western blot.
      The results showed that VES obviously induced cells to undergo apoptosis and
      apoptotic rate after 24 h and 48 h of treatment with VES at 20 micrograms/ml. VES
      was 14.2% and 89.4%, respectively. The expression of p-ERK was evidently reduced
      by VES at 5, 10 and 20 micrograms/ml for 24 h. ERK1/2 was immediately activated
      by VES at 20 micrograms/ml, but the expression was decreased for 2 h, then
      increased again and reached the top level for 12 h. The data implicated that
      ERK1/2 pathway might be involved in VES-induced apoptosis, but in the
      proliferation eventually.

PMID- 14963908
TI  - [Protective effects of vitamin E on the vascular endothelial cells from oxidative
      injury by oxidized low-density lipoprotein in vitro].
AB  - To study the protective effect of vitamin E on vascular endothelial cells (VEC)
      damaged by oxidized low-density lipoprotein(ox-LDL). To establish the oxidative
      injury model of VEC induced by ox-LDL in vitro. The cells were divided into five
      groups(control group, ox-LDL group and VE-L + ox-LDL, VE-M + ox-LDL, VE-H + ox
      LDL group). The cells were protected with varying concentrations of vitamin E
      solution for 24 hours before exposed to ox-LDL. After another 24 hours, the cells
      were collected and relative indexes were determined. The results showed that the
      level of MDA in ox-LDL group was higher than that in the other four groups(P <
      0.05). The activities of SOD in ox-LDL group were lower than that in control
      group and three VE treated groups(P < 0.05). The activities of GSH-Px in ox-LDL
      group and VE-L + ox-LDL group were lower than that in other groups(P < 0.05).
      Vitamin E can prevent vascular endothelial cells from oxidized low-density
      lipoprotein induced oxidative injury.

PMID- 14963909
TI  - [Study on the anti-oxidation function of nucleic acids].
AB  - To study the anti-oxidation function of nucleic acids both in animal experiment
      and in human. (1) Anti-oxidation test in aged rats: Using 32 aged female SD rats,
      divided into 3 dose groups and 1 control group. Each group had 8 rats. Mixing
      deferent doses nucleic acid capsule with drinking water and fad doses groups for
      50 days. The control group was given only drinking water. On 51st day, measuring
      the serum malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione
      peroxidase(GSH-Px). (2) Eating observation test in aged people: Choosing 120
      volunteers aged 50-65 who came from some community in Shanghai, divided into
      eating observation group and control group. Each group had 60 people. Each people
      ate 6 capsules per day for 60 days. The control group used same capsule except
      nucleic acids. On 61st day, measuring the serum MDA, SOD and GSH-Px. RESULTS:
      Anti-oxidation test in aged rats showed that the concentrations of serum MDA in
      all dose groups are lower than that of the control (P < 0.01). The concentrations
      of serum SOD in low and middle dose groups are higher than those of control (P <
      0.01, P < 0.05). The concentrations of serum GSH-Px in all dose groups are higher
      than those of control (P < 0.01). Eating observation test in aged people showed
      that the concentration of serum SOD in eating observation group is higher than
      that of the control (P < 0.05), the concentrations of serum MDA and GSH-Px have
      no significant compared with the control. The appetite, vigorous and energy of
      eating observation group are significantly improved compared with the control (P
      < 0.05). CONCLUSION: The nucleic acid capsule has anti-oxidation function in aged
      female SD rats. The nucleic acids alone could promote SOD and improve the
      appetite, vigorous and energy of human body.

PMID- 14963910
TI  - [Studies on cancer chemoprevention by tea pigments].
AB  - The present study was to investigate the chemopreventive effects of tea pigments.
      In vitro study showed that tea pigments induced QR activity and GST activity in
      Hep G2 cells. Three animal models were used to observe the preventive effects of
      tea pigments on liver cancer, colorectal cancer and oral cancer. Oral
      administration of 0.1% tea pigments increased GST activity in rat liver by 18%,
      and this increase was accompanied by the significant increase of GST 1-1, 1-2,
      and 3-3 protein expression in rat liver. Tea pigments inhibited the proliferating
      cell nuclear antigen labeling index (PCNA-LI), the expression of Bcl-2 protein
      and ras-p21 protein, and induced the expression of Bax protein in rat colorectal
      cancer. PCNA-LI, silver-stained nucleolar organizer regions (AgNOR) and epidermal
      growth factor receptor (EGFR) expression were also inhibited by tea pigments in
      hamster oral cancer. Our results suggested that tea pigments had chemopreventive
      effects on cancer, and the anti-cancer properties may be due to the activation of
      detoxifying enzymes such as QR and GST, the inhibition of cell proliferation and
      the induction of apoptosis.

PMID- 14963911
TI  - [90-day subchronic toxicity study of aloe whole-leaf powder].
AB  - 90-day subchronic toxicity study of aloe whole-leaf powder was conducted to
      observe the effect of aloe whole-leaf powder on health. 88 SD rats were divided
      randomly into 4 groups, and each group consisted of 11 males and 11 females. The
      animals in group 2-4 received aloe whole-leaf powder mixed in regular rodent diet
      at doses of 2, 4 and 8 g/kg BW (by rate of 2.5, 5 and 10 percent in diet) for 90
      days. The animals in group 1 received the regular rodent diet. The results showed
      that aloe whole-leaf powder promoted defecation of rats. Food efficiency and body
      weight males exposed to 8 g/kg BW were significantly less than those of the
      controls. Food efficiency males exposed to 4 g/kg BW was significantly decreased,
      but body weight was not affected. No adverse effect were observed on food
      efficiency and body weight by males exposed to 2 g/kg BW and all exposed groups
      of females. Relative kidney weight was significnatly increased in males exposed
      to 8 g/kg BW and females exposed to 2 g/kg BW or greater. Relative testis weight
      of rats exposed to 4 and 8 g/kg BW were significantly increased compared to the
      control groups. Aloe whole-leaf powder at the dose of 2, 4 and 8 g/kg BW did not
      have adverse effect on hematology, serum AST, ALT, TC, TG, Cr as well as NAG
      activity of urine, serum BUN was significantly increased at the dose of 8 g/kg
      BW. Pathology findings: the incidences of pigmentation in renal tubular,
      mesenteric lymph nodes and lamina propria of the colonic mucosa, and
      proliferation in mesenteric lymph nodes were significantly increased at all of
      the exposed groups, but no pigmentation in colonic mucosa was observed at the
      dose of 2 g/kg BW. No pathological changes were observed in livers, spleens,
      testes (or ovaries). It was concluded that observed adverse effect level of aloe
      whole-leaf powder was 2 g/kg BW (LOAEL of aloin was 11.8 g/kg BW).

PMID- 14963912
TI  - [Study on the role of glucosamine hydrochloride in the pathogenesis of
      osteoarthritis].
AB  - The role of glucosamine hydrochloride in the pathogenesis of osteoarthritis in
      animal models of sponge granuloma, Kaolin arthritiaand and adjuant arthritis was
      studied. The results showed that glucosamine hydrochloride inhibited granulation,
      delayed immunoreactivity, immunological-reative arthritis in daily doses of 0.25
      0.75 g/kg BW orally and vascular oozing, tissue swelling and cell isolating in
      daily doses of 0.5-1.5 g/kg BW orally, indicating that glucosamine hydrochloride
      might have a preventive and theraputic effect on osteoarthritis.

PMID- 14963913
TI  - [Nested case-control study on riboflavin levels in blood and urine and the risk
      of lung cancer].
AB  - The present study is designed to explore the relationship between the riboflavin
      levels in blood and urine and the risk of lung cancer among miners in Yunnan Tin
      Corporation(YTC) by means of nested case-control design. Cases were patients with
      lung cancer newly diagnosed from 1992 to 1995. For each case, 2 controls were
      randomly matched with occupational exposure history, age, the time of collecting
      blood or urine samples. The indexes for evaluating the riboflavin nutritional
      status were erythrocyte glutathione reductase activation coefficient (EGR-AC) and
      the ratio of riboflavin and creatinine in urine. When analyzed as either the
      continuous or the rank variables, the odds ratios(ORs) used to estimate the
      relative risk of lung cancer have no statistical significance(P > 0.05) after
      adjusting the confusing factors. No association of riboflavin indexes in blood
      and urine with the lung cancer risk among YTC miners were observed in the present
      study.

PMID- 14963914
TI  - [Study on protective action of lycium barbarum polysaccharides on DNA imparments
      of testicle cells in mice].
AB  - To investigate the protective effect of lycium barbarum polysaccharides (LBP) on
      DNA oxidative damage of testicle cells induced by hydrogen peroxide (H2O2). The
      single cell gel electrophoresis(SCGE) was used to detect the breakage of DNA
      strand and analyze LBP protection against oxidation damage in testicle cells
      treated by different concentrations of LBP for 1 hour firstly, and then cultured
      with 100 mumol/L H2O2 for 25 min. The results showed that a certain moment action
      by H2O2 could induce the breakage of DNA strand. The pretreatment of LBP (50,
      100, 200, 400 micrograms/ml) significantly decreased the frequencies of cells
      with tail moment and the tail length of testicle cells treated by H2O2. It is
      suggested that LBP itself could not cause the oxidation damage, but it could
      clean out the free-radical and restrain the DNA damage of testicle cells caused
      by the oxidative stress.

PMID- 14963915
TI  - [Study on the production of citrinin by Monascus strains used in food industry].
AB  - In order to screen strains with less or nearly no production of citrinin, thirty
      five Monascus strains used in food industry were selected to investigate the
      effect of cultivation condition and the medium composition on citrinin
      production. The results from the study indicated that all strains produced
      citrinin on the rice with the levels ranging from 0.28 to 2458.80 mg/kg (201.60
      mg/kg for the average and 61.99 mg/kg for the median, respectively), while 30
      strains (85.71%) yielded this toxin on the submerged culture with the
      concentration between 0.09 and 55.65 mg/kg (11.99 mg/kg for the average and 3.51
      mg/kg for the median, respectively). Therefore, citrinin production in rice in
      this study was higher than that in the liquid. In addition, the red pigment
      production in rice was 3-509 (average 93) times higher than that in the liquid.
      One strain with the highest color value (1134 U/g) but lower citrinin production
      in rice was obtained. These results suggested that it is necessary to make the
      safety evaluation of microorganisms for the production of foods and food
      ingredients, to investigate the ability of citrinin production by Monascus
      strains preserved by either the food manufacturer or the national culture
      collection units and, to survey the citrinin contamination in Monascus products
      countrywide. It is urgent for China to establish the tolerance limit of citrinin
      in foods fermented by Monascus species.

PMID- 14963916
TI  - [Studies on the polyclonal antibody and the double-antibody enzyme-linked
      immunosorbent assay against E. coli O157 in food].
AB  - The polyclonal antibody (PcAb) for E. coli O157:H7 was available by intravenous
      injection with New Zealand rabbit with E. coli O157:H7 ATCC43895 strain. Together
      with the monoclonal antibody (McAb) 3A5 specific against E. coli O157 and
      O113:H21, a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA)
      was developed with the as the capture antibody and the McAb 3A5 as the detection
      antibody. The detection limits are 10(3)-10(4) cfu/ml in pure culture of E. coli
      O157 and without any cross reaction with the non-O157 strains. With 10 h
      enrichment procedure, E. coli O157:H7 recovered well from inoculated ground
      poultry meat and pasteurized milk at levels of 0.1 cfu/g(cfu/ml). The results
      demonstrated that the double-antibody sandwich ELISA is a sensitive and specific
      method for detecting E. coli O157 in food samples.

PMID- 14963917
TI  - [Associations of Bsm1 polymorphism of the vitamin D receptor gene and blood lead,
      zinc protoporphyrin, and physical development in 476 environmental lead-exposed
      children].
AB  - The associations of the Bsm1 polymorphism of vitamin D receptor gene and blood
      lead, zinc protoporphyrin and physical development in 476 environmental lead
      exposed children were studied. After blood lead level, age, sex and education
      level of the patients were adjusted by analysis of covariance, the children with
      B allele had larger head circumference than those with bb genotype(P = 0.02).
      While the subjects were stratified by blood lead level and sex, the statistically
      significant difference in head circumference between different Bsm1 genotypes was
      found only in high-blood-lead subgroup and in male subgroup. No significant
      influence of Bsm1 polymorphism on blood lead level, zinc protoporphyrin, height
      and weight was found, suggesting that the Bsm1 polymorphism of VDR gene may
      modify the effect of lead on the skull development of children highly exposed to
      lead.

PMID- 14963918
TI  - [Epidemiological study of occupational injuries in one steel company].
AB  - In order to explore the epidemiological characteristics and accident reasons of
      occupational injury, the data of Occupational injuries in the steel plant during
      employment from January 1988 to December 2001 were analysed. By retrospective
      analysis for the 14 year data of occupational injury, we found the decreasing
      trend of incidence of occupational injury in steel industry, male has greater
      incidence of occupational injury than female, the shorter of duration of
      employment means a greater incidence of occupational injury. The major body part
      of occupational injury are the head and extremity, the major nature of injury are
      burns and fracture. The most cause of injuries are violation of regulation and
      distraction of attention by the victim himself or herself, the next reasons are
      the limitation of equipments and the bad condition of production.

PMID- 14963919
TI  - [An improved high performance liquid chromatography method for determination of 1
      hydroxypyrene in urine].
AB  - A method for determination of 1-hydroxypyrene in urine by alkaline hydrolysis and
      high performance liquid chromatography was improved and validated. The conjugated
      1-hydroxypyrene in urine samples was decomposed by sodium hydroxide. The urinary
      1-hydroxypyrene were extracted by dichloromethane, separated on reverse phase C18
      and detected by fluorescence detector. Internal standard method was applied for
      the quantification of 1-hydroxypyrene. The standard curve was linear over the
      range 10-500 micrograms/L with a correlation coefficient > 0.999. The limit of
      detection and of quantification were 0.01 ng(signal to noise = 3) and 1.0
      microgram/L urine, respectively. The recovery from the entire procedure was found
      to be 94.0% at 5 micrograms/L and 99.5% at 20 micrograms/L. The intra-day RSD
      values were found to be 6.2%, and 5.8% at 5, and 20 micrograms/L respectively
      (all at n = 6). The inter-day RSD values were 7.5%, and 8.9% for 5, and 20
      micrograms/L, respectively (all at n = 6). This method is sensitive, efficient
      and reliable, and was successfully used for the determination of 1-hydroxypyrene
      in urine of workers exposed to polycyclic aromatic hydrocarbon.

PMID- 14963920
TI  - [Effect of zinc on reproductive toxicity in rats].
AB  - The purpose of this study was to explore the effect of zinc on reproductive
      function in rats. The results revealed that the sperm count, sperm motility and
      reproductive function appeared to be enhanced in male rats by 60 days successive
      administration of low dose zinc (12 mg/kg) or medium dose zinc (120 mg/kg),
      whereas reproductive system damages characterized by lowering of reproductive
      function would be resulted by high dose zinc(240 mg/kg). However, no effect on
      the growth and development of the second generation was shown, suggesting that
      the injury was just limited to certain extent.

PMID- 14963921
TI  - [Solid phase microextraction and derivatization of sulfide in blood with
      pentafluorobenzylbromide].
AB  - Solid phase microextraction (SPME) and derivatization with
      pentafluorobenzylbromide for sulfide in blood was presented in the paper. The
      derivative of sulfide was extracted for 20 min at the condition of room
      temperature by a polydimethylsiloxane fiber. 1,3,5-tribromobenzene (IS) was used
      as an internal standerd. GC/MS was used for analysis. The ions at m/z 394
      (derivative of sulfide) and m/z 312 (IS) in the selected ion minitoring
      chromatograms were selected for quantitation. The compound was detectable at
      least 0.01 microgram/ml. By the determination in poisoning blood, this method
      would be demonstrated to be simple.

PMID- 14963922
TI  - [Starch digestion and glycemic indexes].
AB  - After determined carbohydrate classification, two biscuits products, were
      evaluated glycemic indexes (GI) and insulin indexes (II). The analytical results
      showed that the two biscuits were with lower water content and higher lipid than
      bread. In term of carbohydrate (CHO), the ratio of slow digestible starch (SDS)
      and resistant starch (RS) to total CHO for two biscuits (> 60%) were higher than
      bread (18.3%), although the sugar content were also higher. Contrast to GI and II
      value of glucose (as 100%), the GI and II for bread was 96.2% and 105.2%,
      respectively. The GIs for both biscuits were lower than 55%, as well as the IIs
      lower than 73%. It was showed that carbohydrate classification determination is a
      good way for food industry to produce products with ideal GI value.

PMID- 14963923
TI  - [Determination of sulfamethazine and sulfamethoxazole in muscle of chicken by
      high performance liquid chromatography].
AB  - Sulfamethazine and sulfamethoxazole in muscle of chicken was extracted by mixture
      of acetonitrile and chloroform. After being clean up, they were determined by C18
      column using HPLC at 270 nm. The liquid of 0.01 mol/L phosphate
      buffer:methanol:acetic acid (75.9:23:1.1) was used as the mobile phase. The
      recovery of sulfamethazine was 74.7%-86.5%. The RSD was 3.6%-7.9%. The recovery
      of sulfamethoxazole was 74.7-86.5%. The R.S.D was 3.5%-7.9%.

PMID- 14963924
TI  - [Molecular biology of aflatoxin biosynthesis].
AB  - This review provides several important breakthroughs on the molecular biology of
      aflatoxin biosynthesis and information on the regulation and evolution of the
      aflatoxin pathway, and the elimination of the toxin from the food chain as well.

PMID- 14963925
TI  - Boom in Latin American and Caribbean elderly population. Region's health systems
      have 10 years to prepare for rising number of elderly, report warns.

PMID- 14963926
TI  - [Development of rat embryos after prolonged irradiation of ovocytes at the stage
      of immature follicles].
AB  - It was shown that the prolonged low-dose irradiation (up to 0.6 Gy) of the
      immature ovocytes of young rats (21-28 days old) caused delay of development of
      preimplantation embryos after fertilization of ovicells.

PMID- 14963927
TI  - [Dynamics of structural changes in rat liver after single dose of gamma
      irradiation].
AB  - Histological changes and alterations in biophysical and biochemical parameters in
      liver of gamma-irradiate rats have been investigated. The gamma-irradiation of
      the whole body of rats with a single dose of 1 Gy did not cause any impairments
      of beam structure of rat liver, but resulted in the lymphocytic infiltrations of
      portal tracts which were not accompanied by formation of spotty areas of necrosis
      in adjacent areas of lever parenchyma. gamma-Irradiation stimulated proliferation
      of the hepatocytes and induced time-dependent mitochondrial structure lesions.
      Post-irradiation changes in cell cytoplasm appeared as disordering in reticulum
      endothelial system, among them enlarging and fragmentation of its cisterns,
      cytoplasmic vacuolization, enhancement of the number of lysosomes and of the
      lipid inclusion contents. These facts revealed the mobilization of the additional
      energy resources for recovery of metabolic processes in rat liver. Post
      irradiation increase of the level of the hepatocyte membrane lipid peroxidation
      products preceded liver morphological alterations. The membrane lipid
      microviscosity decreased in 1 and 3 days after irradiation. As a result of
      damages of hepatocyte membrane, the activity of the alanin- and asparagin
      aminotransferases in blood serum increased 6 hours after. We can conclude that
      the whole body single gamma-irradiation with a dose of 1 Gy leads to the
      reversible but significant damages to the rat liver cell membrane structures.
      These damages might be the reason of radiation-induced liver morphological
      alterations.

PMID- 14963928
TI  - [Interrelations between the content of reactive oxygen species and the state of
      DNA structure in bone marrow cells of mice after whole body gamma-irradiation].
AB  - The aim of the research is a further analysis of a problem concerning two
      (regulatory and damaging) functions of reactive oxygen species (ROS) in viability
      of organism cells under acute exposure to ionizing radiation. For this purpose
      the ROS content and the state of DNA structure in bone marrow cells of male CBA
      and SHK mice have been studied in dynamics, from 15 minutes up to 185 day after
      acute exposure to a sublethal dose (1.5 Gy) of ionizing radiation. The analysis
      of dependencies between these parameters in the norm, immediately after
      irradiation and in later cell descendants showed the direct correlation between
      the ROS content and the DNA nativity in the norm; 185 days after irradiation the
      correlation disappeared. It was suggested that the correlation occurred in the
      norm indicates participation of the ROS (as a sensory link) in a system of
      reactions (under the control of the corresponding genetic program), that ensure
      the DNA structure and, ultimately, the genome stability. The loss of such
      connection after acute exposure to ionizing radiation indicates actuation of
      another module of reactions sustaining stability of cellular genome in new
      conditions, without regulatory participation of ROS, that can promote or
      demonstrate the development of radiation-induced genome instability.

PMID- 14963929
TI  - [Investigation of conformational changes of DNA molecule caused by gamma
      irradiation in water-ethanol solutions].
AB  - The intrinsic viscosity, optical anisotropy and spectral properties of DNA
      molecule gamma-irradiated with the doses of 10, 20 and 30 Gy in water-ethanol
      solutions with ethanol concentrations 0-6 mol/l are investigated in the work.
      Specific volume of DNA at all doses used shows a complex non-monotone dependence
      on the ethanol content with a peculiarity at the alcohol concentration
      corresponding to the destruction of water structure in the mixed solvent (so
      called, critical concentration, 3.5 mol/l). Ethanol presence at the
      concentrations below the critical one protects macromolecule from the radiation
      action. At the alcohol concentrations larger the critical an inversion of the
      dose dependence of the DNA specific volume is observed. At that the equilibrium
      rigidity and secondary structure of macromolecule do not change noticeably. The
      results obtained indicate a significant role of the solvent structure in
      radiation damage of DNA molecule.

PMID- 14963930
TI  - [Effect of subtherapeutic doses of docetaxel (taxotere) on the efficacy of
      radiotherapy and pro-oxidant-antioxidant balance in rats with Guerin's
      carcinoma].
AB  - In the experiments at Wistar male rats the effect of subtherapeutic doses of
      docetaxel (5 and 10 mg/kg) on the radiotherapy efficacy (20 Gy of single-dose X
      rays) namely growth rate of Guerin's tumor and prooxidant-antioxidant balance in
      liver and blood of animals bearing tumors was investigated. It has been
      demonstrated that docetaxel at dose 5 mg/kg given 18 hours before irradiation
      resulted in significant tumor growth delay (2.3-2.7-fold) in comparison with
      group of rats that received only irradiation. After application of higher dose of
      docetaxel there was no statistically significant change of tumor size along the
      whole experiment (14 and 21 days after tumor implantation). Content of lipid
      peroxidation products was revealed to be considerably increased after
      chemotherapy and concurrent irradiation when docetaxel was used in a dose of 10
      mg/kg. At the same time glutatione peroxidase activity and antioxidative activity
      of blood plasma were reduced. In the rat liver chemoradiotherapy led to decrease
      of glutathion peroxidase and glutathione-S-transferase activity to greater degree
      at docetaxel dose of 10 mg/kg. The obtained results allow to conclude that higher
      dose of docetaxel and concurrent irradiation resulted in the most effective
      Guerin's carcinoma growth delay and considerable deviation of antioxidant
      prooxidant balance of tissues in the direction of the last.

PMID- 14963931
TI  - [The radiation-modifying capacity of xenogenic apotransferrin for the number of
      endogenous colony forming units in the spleen of irradiated mice].
AB  - After intraperitoneal injection of 100 or 198 mg/kg of human serum apotransferrin
      (apo TF) to mice 1 day before acute exposure to 6 Gy of gamma-radiation, the
      number of endogenous CFU in spleen (CFUs) increased 2.5 or 2.6 times
      respectively. At a dose fo 10 mg/kg of the protein only an increasing tendency
      was found, whereas a dose of 1 mg/kg was inefficient. A dose of 100 mg/kg of BSA
      did not show any effect suggesting that non-specific immune response to alien
      antigen did not contribute to apo TF radiomodifying action. The following
      mechanisms of the apoTF radiomodifying effect are discussed: 1) the ability of
      the protein to inactivate Fe3+ ions that reduces the consequences of radiation
      oxidative stress; 2) the stimulation of proliferation of the exposed bone marrow
      cells by activation of Fe3+ transport or by Ca2+ mediated mechanism of mitogen
      signal transduction; 3) changing in the content and ratio of cyclic nucleotides
      by apo TF stimulation of Ca-calmodulin-dependent phosphodiesterase.

PMID- 14963932
TI  - [Modifying action of Mn(II) chelate with ethyl ester of salicylydene tyrosine on
      some biophysical parameters of erythrocyte membranes of the irradiated organism].
AB  - The presentation summarizes the results of studies on radioprotective activity of
      newly synthesized Mn(II) chelate with ethyl ester of salicylydene D,L-tyrosine,
      basing on the evaluation of its membrane-protective effects, revealed at
      different periods post the exposure of the organism to ionizing radiation. It was
      revealed that the administration of the compound into the animal organism before
      the radiation exposure (gamma-irradiation of 60Co at a dose level of 4.8 Gy)
      produced correcting action on structure-functional properties of erythrocyte
      membrane of irradiated rats: the excessive activation of lipid peroxidation of
      erythrocyte membranes was inhibited, the passive permeability of erythrocytes for
      K+ ions was normalized, the deformity and membrane potential of erythrocytes
      according to hydrogen-chlorine gradient were recovered.

PMID- 14963933
TI  - [Study of formation and elimination of 8-oxoguanine in DNA of the liver and brain
      of mice after gamma-irradiation].
AB  - 8-oxoguanine (8-OG) is a biological marker of oxidative damage to DNA by reactive
      oxygen species. With the help of monoclonal antibodies to 8-OG, by the method of
      chemiluminescence enzyme immunoassay essential distinctions were found in
      formation and elimination of this damage to DNA in a liver and brain of mice
      exposed to 20 Gy of gamma-radiation. A spontaneous level of 8-OG in DNA of brain
      is much higher than in DNA of liver. Registered immediately after the exposure,
      the induction of 8-OG in DNA was approximately 3 times greater in brain than in
      liver. Elimination of 8-OG from DNA of both tissues proceeds more actively only
      during 30 min after the exposure, and the significant percentage (26-30%) of
      these damage is kept in DNA of the tissues for 3 hours after the exposure. The
      levels of lipidsoluble antioxidants, determined by the reaction with a stable
      free radical, in tissues of mice do not correlate with a quantity of 8-OG,
      arising in DNA spontaneously and under irradiation.

PMID- 14963934
TI  - [Time- and dose-dependent post-irradiation changes of Fe3+-transferrin and Cu2+
      ceruloplasmin pools in blood, their influence on ribonucleotide reductase
      activity in animal tissues and the effects of radioprotectors].
AB  - The time- and dose-dependent changes of Fe(3+)-transferrin (Fe(3+)-TF) and Cu(2+)
      ceruloplasmin (Cu(2+)-CP) pools, of superoxide dismutase activity and the
      inhibitory activity of alpha 2-macroglobulin in blood as well as changes in
      synthesis rates of deoxyribonucleotides (dNTP), DNA and proteins in organs
      (spleen, liver, bone marrow, thymus) of mice and dogs given total body
      irradiation have been studied using of ESR spectroscopy, radioisotope techniques
      and biochemical determination of enzymatic activity. The experimental data have
      allowed us to reveal the sequence of organism's response reactions against
      irradiation and their modifications by radioprotectors. Changes in blood Fe(3+)
      TF pool is one of the most informative, highly radiosensitive and rapidly
      reactive marker against irradiation and drug administrations. This irontransport
      protein controls a rate-limiting iron-dependent stage for DNA synthesis--the
      synthesis of dNTP, catalyzed by iron-containing ribonucleotide reductase (Fe(3+)
      RR). It has been shown that time-dependent post-irradiation changes of Fe(3+)-TP
      pool in blood are characterized by three distinct stages: 1) the prompt increase
      of pool (SOS-type response) playing the important role in protecting of cell's
      genetic apparatus from damage; 2) the decrease of its pool within 3-18 h after
      irradiation resulting in the loss of Fe(3+)-RR activity in tissues of blood
      forming organs that make more stronger radiation-induced damage; 3) the following
      phase-dependent increase in Fe(3+)-TF pool at the 2-nd, 6th, 10-17th days after
      irradiation due to an increase in transferrin synthesis. This increase may be
      considered as compensatory reaction of blood-forming organs directed at restoring
      blood and organ's cells. The time-dependent courses of the reactions are
      independent from radiation doses indicating to the universal and nonspecific
      response of organism against irradiation. But, the intensity of this compensatory
      adaptive response at 2-nd and 6th days grows with increasing radiation dose up to
      lethal that, and organism's response becomes abnormal and physiologically
      hypertrophic. The prolonged "stressful syndrome of biochemical tense state"
      should be attributed to negative effects for organism, since it may result in the
      failure of compensatory adaptive organism's reactions and animal killing. The
      radioprotectors ward off the appearance of this dangerous state. Dogs with
      initial individual characteristics of blood which were typical for "suppressed"
      or "activated" states had abnormal response against irradiation by low doses 0.25
      or 0.5 Gy. In these cases the intensity of response reactions of organism was
      essentially increased and markedly deviated from linear dose dependence. The
      phase-dependent increase of Fe(3+)-TF pool in blood in post-irradiation time
      resulted to the increase of Fe(3+)-RR activity in blood-forming organs. The key
      event ensuring the development of compensatory adaptive reactions is the increase
      of capacity of protein-synthesizing apparatus, the activation of biosynthesis of
      dNTP and DNA against the treatment with damaging factors.

PMID- 14963935
TI  - [Effects of the microwave exposure at elevated ambient temperature on the thermo
      compensatory responses of small laboratory animals].
AB  - Thermogenic effectiveness of electromagnetic irradiation (EMI) of UHF range (7
      GHz) in the dependence on intensity (10-50 mW/cm2) and environmental temperature
      (22 degrees and 30 degrees C) was studied in experiments with mice and rats.
      Negative influence of high ambient temperature on thermoregulate responses of
      animals at microwave exposure was showed. It is concluded that this interaction
      should been taken into account for hygienic standardization of non-ionizing EMI.

PMID- 14963936
TI  - [Estimation of long-time effects of Chernobyl AES accident on behavior markers in
      a small rodent population].
AB  - Differences in behaviour reactions in "open field" and glycemia under conditions
      of immobilisation stress of vole (Microtus oeconomus, Pallas) from two groups
      ("Yanov" and "Lelev") were investigated. Rodents were ensnared from two
      populations reproduced for a long time (11 years) in the areas of ChNPP Exclusion
      Zone with different level of radioactive contamination. The radiation absorbed
      dose for animals of "Yanov" group (external and internal irradiation) was 11-20
      times higher than that of "Lelev" group. Males and females from the area with
      worse radioecological condition had higher vertical and horizontal locomotion.
      The level of emotional reactions of "Yanov" males was lower than the "Lelev" one.
      Statistically significant variation in female emotional reaction was found, but
      it had not the same directions. In both groups higher locomotion activity and
      lower emotionality were associated with male sex. The males of both groups showed
      similar fasting glucose level and glycemic response after 30-min. immobilisation.
      Our data provide the additional evidence of existence of long-time genetic
      effects in small rodent populations permanently reproduced on radiation
      contaminated areas.

PMID- 14963937
TI  - [Method of quantified complete estimation of soil properties for prediction of
      radionuclide accumulation by plants].
AB  - A method is founded on consideration of soil as three-phase system where soil
      solution reaction (pH), absorbing capacity (E) and content of organic matter (OM)
      are the main characteristics. The method of complete estimation of soil
      properties (CESP) for quantified analysis of radionuclide soil-to-plant TF
      dependence on soil properties is grounded and proposed. The area of an effective
      section (relative units)2 calculated as an area of the triangle with apexes lying
      in co-ordinates of normalised vectors pH, E and OM in three-dimensional space for
      complete estimation is used. It is shown that the dependence of 137Cs TF to
      various crops on CESP can be approximated by equation of power law.

PMID- 14963938
TI  - [Chemical-toxicological characteristic property of organochlorine pesticide
      transformation products formed under the effect of intensive fluxes of gamma
      irradiation].
AB  - The results of formation of stable products of organochlorinated pesticides (OCP)
      under gamma-irradiation (dose 10 kGy, dose rate 0.026, 0.14 kGy/min) are
      discussed in the article. The model solutions of alpha-,gamma
      hexachlorocyclohexane (alpha-,gamma-HCH), p,p-dichlorodiphenyl-trichloroethane
      (p,p-DDT) and p,p-dichlorophenyl-dichloroethylene (DDE), with initial
      concentrations of 1.0-0.1 ppm, were exposed to gamma-radiation. Among the
      products of OCP radiolysis such compounds as DDE, 2,2-di(chlorophenyl)-1
      chloroethylene, dichlorophenyl-dichloroethane and various isomers of HCH were
      found. It was shown that taking in account the whole data on the formed
      metabolites the toxicological characteristics of pesticide solutions cannot be
      improved by exposure to gamma-radiation.

PMID- 14963939
TI  - UK university shelves plans for primate research lab.

PMID- 14963940
TI  - Heart of the matter.

PMID- 14963941
TI  - On the mark. Interview by Dina Leifer.

PMID- 14963942
TI  - Runaway success.

PMID- 14963943
TI  - Play to learn.

PMID- 14963944
TI  - Spare parts sale.

PMID- 14963945
TI  - Nursing patients with ARDS in the prone position.
AB  - This article examines the main features of acute respiratory distress syndrome
      (ARDS), including the pathophysiology, clinical manifestations, complications and
      treatment. Patients with ARDS are critically ill and require close monitoring and
      mechanical ventilation in an intensive care unit. The benefits of prone
      positioning, one of the main treatment options for these patients, are discussed
      in detail. By understanding the physiological principles that underpin the prone
      position, the critical care nurse will be more effective in identifying patients
      who might benefit from this treatment.

PMID- 14963946
TI  - Clinical protocols for stoma care: 6. Management of parastomal hernia.

PMID- 14963947
TI  - Hodgkin's lymphoma.
AB  - Hodgkin's lymphoma is a malignant disease of the lymphatic system. This article
      gives an overview of the disease process and the classification and staging of
      Hodgkin's lymphoma. The nursing care and psychological support of these patients
      during radiotherapy and chemotherapy treatment are also discussed.

PMID- 14963948
TI  - Your flexible friend.

PMID- 14963949
TI  - Speaking up for children. Interview by Catharine Sadler.

PMID- 14963950
TI  - Prescription drugs uses and effects. Antibacterial drugs.

PMID- 14963951
TI  - DNR case highlights ethical dilemma.

PMID- 14963952
TI  - Should junk food advertisements be banned?

PMID- 14963953
TI  - The experience of being a suspended nurse.

PMID- 14963954
TI  - A passion for learning. Interview by David Crouch.

PMID- 14963955
TI  - 'Being there with patients is a privilege'.

PMID- 14963957
TI  - What you need to know about ... ringworm.

PMID- 14963956
TI  - Childhood obesity: its incidence, consequences and prevention.
AB  - In 1998 the World Health Organization declared childhood obesity a 'global
      epidemic' (WHO, 1998). The Department of Health has identified that prevention
      must be aimed at children to address its rise in future generations (DoH, 2002).
      Childhood obesity is recognised as a predictor of adolescent and adult obesity
      (Smith, 2002; Parsons et al, 1999; Whitaker et al, 1997). Without intervention to
      prevent the growing trend of childhood obesity there is a risk of increasing
      economic cost and human suffering in future generations (Laing, 2002).

PMID- 14963958
TI  - Access to secondary care for people with learning disabilities.
AB  - A person-centred approach is needed to improve access to secondary health care
      for people who have learning disabilities. The Department of Health (1995a) drew
      attention to this issue when it reported that people with learning disabilities
      sometimes have problems maintaining their health because hospitals fail to work
      in an interdisciplinary manner with the specialist learning disability services.
      This article focuses on a case study where the difficulties in operating on a
      patient with learning disabilities and mental health problems were overcome
      through a multidisciplinary and patient-centred approach. The case study provides
      evidence of mainstream health staff and learning disability professionals working
      together and breaking down barriers to provide a seamless service.

PMID- 14963959
TI  - Piloting a nurse-led gynaecology preoperative-assessment clinic.
AB  - This article outlines a pilot project to develop and evaluate a nurse-led
      gynaecology preoperative-assessment clinic at an acute hospital trust. The main
      aim of the clinic was to offer an effective preoperative-assessment service that
      provided high quality individualised and sensitive patient care. Further aims
      were that the clinic could be a template for other preoperative-assessment
      clinics, an educational resource for staff, a tool for clinical nursing career
      progression and a service to help ease junior doctors' workloads.

PMID- 14963960
TI  - Barriers to the provision of effective pain management.
AB  - Despite major advances in the management of pain since the Royal College of
      Surgeons and the Royal College of Anaesthetists announced in 1990 that
      postoperative pain management in British hospitals was inadequate, pain continues
      to be an unacceptable but common sequel to surgery (Wood, 2002). Pain assessment
      is simple, but unfortunately it is infrequently performed. When clinicians do not
      obtain pain ratings from patients they are unlikely to underestimate the
      patients' pain. Improving pain management requires that pain is recognised as a
      priority and that nurses are encouraged to play an active and pivotal role within
      the multidisciplinary team to recognise, prevent and treat it.

PMID- 14963961
TI  - Delivering care in extreme conditions. Interview by Victoria Hoban.

PMID- 14963962
TI  - [New prevention strategies against breast cancer and cervical carcinoma. What can
      you advice to your patients].

PMID- 14963963
TI  - [Interview with Prof. Dr. Wolfgang Eiermann. Which women need a medicamentous
      breast cancer prophylaxis?].

PMID- 14963964
TI  - [Modern strategies of infarction prevention in hypertensives and diabetics. Salt
      and sugar -- both are risky for the heart].

PMID- 14963965
TI  - [Influenza deaths in the USA, overcrowded clinics in France. Dangerous influenza
      virus on the march?].

PMID- 14963966
TI  - [Gastroesophageal reflux. Endoscopic control is mostly unnecessary].

PMID- 14963967
TI  - [Investigating chronic diarrhea. Clarify matters by talking to the patient].

PMID- 14963968
TI  - [Diarrhea as manifestation of allergic diseases. The difficult search for the
      allergen].
AB  - Allergy is a very uncommon cause of diarrhoea. Other mechanisms, medical diseases
      and infections, psychological and pseudoallergic reactions, intolerance
      reactions, and enzyme defects/deficiency, and many other conditions are much more
      common. If food allergy is strongly suspected diagnosis may be difficult, even
      for allergologists, as it requires a mosaic of history, skin and in vitro tests,
      diagnostic diet, and even provocation tests. It is important to recognise
      diarrhoea "accompanying" allergic urticaria and anaphylactic reactions as part of
      the symptomatology of the primary dermatological or allergic disease and to refer
      the patient to the appropriate specialist.

PMID- 14963969
TI  - [Psychosomatic aspects of chronic diarrhea].

PMID- 14963970
TI  - [Meningitis in children and adults. Differential diagnostic approach and
      management].

PMID- 14963971
TI  - [LDL cholesterol in normal range. The lower the better? Implications of the
      GREACE study].
AB  - The higher an individual patient's risk, the greater the clinical effect of lipid
      lowering drug therapy. According to present guidelines, therapeutic decisions
      should be guided by the patient's overall risk. This depends not only on the LDL
      cholesterol, but also on the number and degree of other risk factors. This paper
      will show that LDL cholesterol before treatment determines the clinical efficacy
      of a statin: for instance, using a statin to lower the LDL cholesterol by one
      third gives a greater risk reduction the higher the baseline value. For a given
      baseline value, greater risk reduction results from a larger reduction in LDL
      cholesterol. LDL cholesterol measurement is thus essential before and on
      treatment.

PMID- 14963972
TI  - [Practice dues without paying cash. What does the physician have to spend for
      it?].

PMID- 14963973
TI  - [Strange reaction of a state secretary. Do we still live in the Empire?].

PMID- 14963974
TI  - [Not only the cost factor but also occupational mover. Every ninth person works
      in the health care system].

PMID- 14963975
TI  - [Blood sugar inspite of maximal metformin dosage. New fixed combination forces
      HbA1c down].

PMID- 14963976
TI  - [Ankle-brachial index to be measured more often. Every fifth patient over 65 has
      peripheral arterial occlusive disease].

PMID- 14963977
TI  - [New therapy of stress urinary incontinence. Syringe instead of knife].

PMID- 14963978
TI  - [After stroke or TIA. Double protection by second platelet inhibitor].

PMID- 14963979
TI  - [Body weight adapted anticoagulation is passe. Thrombosis therapy without
      scales].

PMID- 14963980
TI  - [Enduringly effective and tolerable initial therapy of HIV. Even after 5 years no
      resistance].

PMID- 14963981
TI  - [Are all boosted protease inhibitors the same? Previously treated patients profit
      too from lopinavir/r].

PMID- 14963982
TI  - [The 10-minute consultation. Acute cough].

PMID- 14963983
TI  - [Pruritus -- fatigue -- icterus. Bile obstruction has many faces].

PMID- 14963984
TI  - [A medical art error. Corticoids have lost nothing in the face!].

PMID- 14963985
TI  - [Diabetic nephropathy. Are the blood pressure values set too low?].

PMID- 14963986
TI  - [When after myocardial infarction a pump weakness remains. ACE inhibitors and AT
      1 blockers equivalent].

PMID- 14963987
TI  - [New options against undertreatment].

PMID- 14963988
TI  - [A new disease understanding of fibromyalgia. A patient with scarred psyche].

PMID- 14963989
TI  - [Carrying on after the catastrophe. How psychotherapy can help traumatized
      patients].

PMID- 14963990
TI  - [Diagnosis of trauma sequelae].
AB  - Traumatic events often trigger acute psychosomatic and psychiatric sequelae,
      which sometimes show a tendency to become chronic. The post-traumatic stress
      disorder (PTSD) is a complex syndrome with numerous mental and vegetative
      symptoms. The diagnosis of trauma sequelae requires a good knowledge of the
      differential diagnostically relevant comorbid conditions (e.g. anxiety disorders,
      depressive disorders, and somatoform disturbances). An appropriate management
      plan is possible only when suitable consideration is given to the traumatic
      genesis of symptoms. In the treatment of trauma, a stepped approach involving the
      principles stabilization, trauma processing and psychosocial re-integration has
      proven value.

PMID- 14963991
TI  - [Therapy of post-traumatic stress disorders].

PMID- 14963992
TI  - [Psychotherapeutic treatment of traumatic stress with the EMDR (Eye Movement
      Desensitization and Reprocessing) method].
AB  - EMDR (Eye Movement Desensitization and Reprocessing) is a method, developed at
      the end of the nineteen-eighties, for the treatment of the post-traumatic stress
      disorder (PTSD). The patient is asked to concentrate on certain aspect of the
      traumatic memory while keeping his eyes fixed on the movements of the therapist's
      finger. Apparently, this triggers information processing that results in
      appreciable relief for the patient. The method has proven to be equally as
      effective as behavioral-therapeutic techniques, and, has in the meantime, been
      included in national and international guidelines for the treatment of PTSD. The
      indications for EMDR treatment include not only PTSD, but, increasingly, also
      other, sometimes more severely chronic, it trauma sequelae. Within the framework
      of basic care, EMDR must be embedded within a treatment plan and should, where
      applicable, be combined with other methods.

PMID- 14963993
TI  - [Guidelines for the diagnosis and treatment of H. pylori infection].
AB  - In accordance with our current understanding, infection with the pathogen
      Helicobacter pylori is an important, but readily diagnosable and treatable cause
      of various gastroduodenal diseases. A lasting cure is achieved when the bacterium
      is eradicated with the aid of an established therapeutic regimen. Furthermore,
      eradication is a rational preventive measure even in asymptomatic patients, since
      current clinical data show that it offers protection, in particular to high-risk
      groups, from gastric carcinoma, but also from other complications (e.g. peptic
      ulcer). The upgraded European Guidelines on the diagnosis and treatment of H.
      pylori infection put out by the European Helicobacter Pylori Study Group (EHPSG)
      in Maastricht take account of the present state of our knowledge of the
      significance of H. pylori eradication.

PMID- 14963994
TI  - [Tuberculosis: consider it first. Cough, dyspnea and expectoration are not
      specific symptoms].

PMID- 14963995
TI  - [Little additional expense, great additional use. How a digital camera lightens
      the work].

PMID- 14963996
TI  - [To seize the evil by the roots. Zulu medicine improves cough, sore throat and
      common cold].

PMID- 14963997
TI  - [Even at LDL cholesterol 100mg/dl. "Every coronary disease patient has to receive
      a statin"].

PMID- 14963998
TI  - [From the beginning -- a strong-acting and well tolerable antihypertensive agent.
      The recipe against constant change].

PMID- 14963999
TI  - [An overweight diabetic does not tolerate metformin. Insulin sensitizer can be
      prescribed alone, too].

PMID- 14964000
TI  - [Bronchial asthma. A new steroid acts fast and directly].

PMID- 14964001
TI  - [From aqua jogging to skiing. Advisable sports for patients with arthrosis].

PMID- 14964002
TI  - [Children's vaccinations: the earlier, the better].

PMID- 14964003
TI  - [Acute respiratory tract infection in chronically ill patients. germ spectrum
      different than in healthy persons].

PMID- 14964004
TI  - [Implantable port systems].

PMID- 14964005
TI  - [A present from the tropical Africa].

PMID- 14964006
TI  - Japan deaths spark concerns over arthritis drug.

PMID- 14964007
TI  - [Development of public health law: valuable elements worth sharing].

PMID- 14964008
TI  - [Cultural adaptation and validation of questionnaires measuring satisfaction with
      the French health system].
AB  - Two questionnaires measuring satisfaction of the population with regard to health
      care offer were constructed from measures validated in the USA (the Consumer
      Satisfaction Survey Questionnaire or CSS, and the Visit-Specific Satisfaction
      questionnaire, the VSQ). This work was comprised two stages: i) translation and
      cultural adaptation of the American instrument to the French health care context,
      implicating 6 translators, users and experts; and ii) a telephone survey in the
      general population (n = 706) to test the psychometric qualities of the French
      instrument (content and internal validity). The French version, the CSS-VF
      comprises 9 scales: access to primary care, access to secondary care, scope for
      choice, health cover, communication with and competence of GPs, communication
      with specialists, competence of specialists, human qualities of practitioners and
      overall satisfaction. The VSQ-VF, which measures satisfaction with the last
      medical consultation is unidimensional. The results of the psychometric analyses
      are good overall, and endorse the use of these scales in assessment studies.

PMID- 14964009
TI  - [Communication with sexual partners about the risk of HIV/AIDS infection in
      seamstress apprentices in Benin].
AB  - Communication with sexual partners on the risk of HIV/AIDS infection and its
      relation to risk-taking was examined in a group of young single women who have
      been removed from school and apprenticed to a seamstress in Cotonou, Benin.
      Twenty women aged 15 to 24 were interviewed. Results showed that more than half
      the women had already discussed HIV/AIDS with their partners. This discussion,
      always initiated by the woman, progresses until the ultimate goal is achieved:
      discussion of practicing safer sex. Women who openly communicated with their
      partners possessed certain common characteristics (e.g. they were born in
      Cotonou, seeking marriage or financial assistance, had a perception of risk, had
      discussions with friends). Those who communicated the most reported that
      practicing safer sex consisted of using a condom, which still remains an
      occasional practice at best.

PMID- 14964010
TI  - [Anemia associated with malaria and intestinal helminthiasis in Lubumbashi].
AB  - The purpose of this study is to evaluate and determine the prevalence of anemia
      and associated factors (malaria and intestinal helminthiasis) in some high risk
      groups, especially in pregnant and breast-feeding women and in children aged 1-2
      years old from within a deprived semi-urban population of Lubumbashi (Bongonga
      and Sendwe). These results were compared to those obtained from an urban
      population having a more satisfying socio-economic situation (University
      Clinics). The overall frequency of anemia in the subjects studied from the three
      centres varies from 50-80%. The proportion of anemic cases is clearly higher in
      the Bongonga and Sendwe populations (70-80%) than in that of the urban group
      (50%) (P < 0.05). Among all of the subjects examined, pregnant women are found to
      be the group with the highest proportion of anemic patients (P < 0.05). All
      things considered, anemia is associated with malaria in 40% of the cases and with
      intestinal parasitism (Ascaris and/or Ankylostome infestation) in 9%. Faced with
      such a situation, the strategy to fight against anemia and associated parasitosis
      demands and requires multi-disciplinary actions centred on health education,
      collective screening and specific anti-parasite treatment.

PMID- 14964011
TI  - [Bibliographic study of the effectiveness of preventive measures in occupational
      asthma].
AB  - Having retrieved information from bibliographical searches as well as through a
      vertical analysis of the health problem, this analysis provided in the article
      points out the effective prevention strategies and interventions for managing
      occupational asthma. There is no scientific evidence on a series of protection
      measures and even less for intervention operationalisation strategies. However,
      considering the increase of the incidence of the disease and its economic and
      social consequences, it is critical that the various concerned actors understand
      the trend of this health problem in order to better comprehend their role in the
      individual and collective prevention strategies.

PMID- 14964012
TI  - [The stakes for hospital organization: users' point of view].
AB  - In France, a hospital must rely upon its patients' perspectives and other users'
      points of view in order to set objectives for the improvement in the organisation
      of care and services provided. This article presents the principle learnings from
      a study conducted on the users' perception of their care received at a university
      hospital centre. Three main results surfaced: a strong expectation of
      consideration which was common among all users; the significance of the care's
      context as a determining factor in the users' opinion on the care received: and
      finally, the level and investment of consideration expected by the users
      simultaneously concerns a number of tasks, namely medical care and follow-up
      services, the moral and emotional relationship of the hospital's staff with the
      users, the catering and cleaning services, the emergency services and the
      hospital's check-out procedures and conditions. This third point could serve as
      mandatory principle in any project aiming to improve the operation of a
      hospital's structure and the organisation of services and care.

PMID- 14964013
TI  - [Medico-economic evaluation of a care management program for asthmatic patients].
AB  - This study aimed at measuring the medico-economic interest of a care management
      programme established for asthmatic patients in the Amiens region ("Action Asthma
      Amieris") by using and comparing different evaluation tools. Three tools were
      used in parallel: 1) a questionnaire for collecting information on healthcare
      received was completed monthly by 305 patients recruited by 73 physicians between
      November 1998 and January 1999; 2) data issued by the national insurance fund for
      the years 1998 and 1999, for those patients included after January 1999; and 3)
      data on all hospitalisations for 1998 and 1999 in the University Hospital Centre
      obtained from the French hospital information database (PMSI). Data from the
      national insurance fund and from the PMSI are essential to evaluate costs, since
      the patients' statements proved to under-estimate the amount of healthcare
      administered and received. Following the implementation of this asthma care
      management programme, an increase of pharmaceutical expenses and a decrease in
      the number of hospitalisations for asthmatic patients were observed.

PMID- 14964014
TI  - [Interest in periodic health examinations for young people in the judicial
      system].
AB  - The Centre for Health Examinations (CES) in Roche sur Yon has experience with the
      Periodic Health Examinations (EPS) on population groups in fragile or
      disadvantaged situations and young people in the process of integration. Minors
      followed by the Judicial Protection of the Youth (PJJ) are in a preoccupying
      state of health. Professionals led a working group for reflection from two
      institutions working in health management. This study aims to explore the
      representations of young people's health under the care of the judicial system in
      order to evaluate the pertinence of EPS in the health course of youth in the
      judicial correctional system. 23 semi-directed interviews allowed the team to
      show that if the youth have a somatic definition of health, they are nevertheless
      open to a comprehensive approach to health. Their parents are unavoidable
      reference points. The readability of the speakers in terms of mental health
      remains average. The resources in health documentation are under-utilised. The
      treating doctor remains a special partner for health. The knowledge of social
      rights is insufficient. The notion of risk and the need for more information
      concerns the areas of drunk driving, sexuality and road rage. The EPS very
      logically places itself in the health course of the youth. The partnership
      between the health and the justice systems should be constructed in the framework
      of a convention between the two institutions.

PMID- 14964015
TI  - [Initial medical training and the health of disadvantaged populations].
AB  - In France and across the globe, there are many underprivileged individuals, and
      their health status is often very fragile and unstable. The medical profession
      has to take a central position to confront these questions based upon its
      professional ethics, in terms of guidelines and duties. Medical professionals
      need to be prepared for tackling this problem. Based upon a survey carried out,
      this article demonstrates that medical students are indeed demanding this type of
      training. Future doctors must learn how to use specific tools and know how to
      integrate their activity in a public health approach, through multi-disciplinary
      work. This is precisely the role and responsibility of the University, as stated
      by the World Health Organization in the Arizona Charter and the creation of the
      UNISOL (University Solidarity) network. At present, many of the French medical
      schools offer courses on this subject in the third year, but it is placed too far
      down the line from the initial medical training, which also has the mission of
      presenting the student with different types and ways of practicing medicine.
      French universities have very limited direct contact with disadvantaged
      communities, and links with various health organisations which do deal with these
      communities are often lacking. However, there are many universities and medical
      schools abroad which have developed and established that which they refer to as
      "Community-oriented Medical Education". It therefore appears to be important that
      new educational axes engage the University in its institutional duty and social
      response especially towards those who are in need the most.

PMID- 14964016
TI  - [Management of children's fever at home in a rural area of Boko (Congo
      Brazzaville)].
AB  - A cross-sectional study on the diagnostic and therapeutic practices of health
      staff and mothers with regards to carrying for children's fever was carried out
      from February 27 to March 16, 1995, in the rural district of Boko. The sample was
      comprised of 630 children aged less than 5 years old, having suffered from fever
      within the past 15 days and who were treated either at home or in a local health
      centre with a drug most presently used against malaria. The results compiled from
      the responses to the questionnaire have shown that the most frequently cited
      symptoms by mothers are fever (57.8%), asthenia (51.7%), vomiting (10.6%), chills
      (7.3%) and diarrhea (7.3%). Chloroquine is the most utilised drug at home (61%)
      and anti-malaria injections are the most frequently used drugs in health centres
      (51.7%). The medicine is mainly supplied by public drugstores and pharmacies
      (47.8%) and street vendors (43.2%). Proper management of a fever requires
      adequate training of health staff and a good level of communication between
      health workers and their target populations.

PMID- 14964017
TI  - [Regionalization of very preterm birth care sites in Ile-de France in 1998].
AB  - The objective of this article is to describe the conditions under which very
      premature babies were born in the Paris region between June 1 and December 31,
      1998, that is to say those born prior to reaching 33 weeks of term (SA) and/or
      having a birth weight less than 1500 grams. The study looked at all pre-term
      births, including medical terminations of pregnancy (TOP), occurring in one of
      the 135 maternity units in the Paris region. Between June 1 and December 31,
      1998, 1337 mothers gave birth to babies prior to reaching 33 weeks of term (SA)
      and/or having a birth weight less than 1500 grams in 84 maternity units in the
      Paris region, 263 of which had a medical termination of pregnancy (20%). These
      mothers were older than average for the region (25% were 35 years old or older);
      4.3% of them do not have social insurance coverage. The remaining 1074 mothers
      (excluding TOP) gave birth to 1290 children, of which 202 were stillbirths, 46
      died in the labor ward and 1042 were admitted to a neo-natal unit. Of the same
      group of 1074 mothers, 195 (18%) had a multiple pregnancy--175 twins, 19
      triplets, and 1 quadruplet 60% of them (599 women) who had very premature or low
      birth weight babies (excluding TOPs) delivered them in a tertiary perinatal
      centre (TPC). This proportion varies according to two variables: 1) the community
      in which the family lives (40% in the Seine-et-Marne department, the eastern
      region of Paris and a district without TPCs, to 70% in the Hauts-de-Seine, a
      northern district), and 2) whether the pregnancy is single (58.8%), twin (72.6%)
      or triple (84.2%). In utero transfer accounts for 62.7% of the mothers who
      delivered in TPC, who were transferred prior to delivery. This type of study is
      useful for measuring the implementation of the regionalisation high-risk
      perinatal care and access to adequate services. It clearly demonstrates that
      inequities in access to care exist for women by district of residence.

PMID- 14964018
TI  - [Structural adjustment, cultural adjustment?].
AB  - Over the last two decades, multiple studies have been conducted and many articles
      published about Structural Adjustment Programmes (SAPs). These studies mainly
      describe the characteristics of SAPs and analyse their economic consequences as
      well as their effects upon a variety of sectors: health, education, agriculture
      and environment. However, very few focus on the sociological and cultural effects
      of SAPs. Following a summary of SAP's content and characteristics, the paper
      briefly discusses the historical course of SAPs and the different critiques which
      have been made. The cultural consequences of SAPs are introduced and are
      described on four different levels: political, community, familial, and
      individual. These levels are analysed through examples from the literature and
      individual testimonies from people in the Southern Hemisphere. The paper
      concludes that SAPs, alongside economic globalisation processes, are responsible
      for an acute breakdown of social and cultural structures in societies in the
      South. It should be a priority, not only to better understand the situation and
      its determining factors, but also to intervene and act with strategies that
      support and reinvest in the social and cultural sectors, which is vital in order
      to allow for individuals and communities in the South to strengthen their
      autonomy and identify.

PMID- 14964019
TI  - [An unsuspected imported disease: meningo-encephalitis contracted in Spain].
AB  - A 13-year-old boy consulted a doctor during a holiday in Spain because of high
      fever, headache and exanthema. A local physician prescribed josamycin, but the
      medication was lost due to vomiting. A few days later, shortly after returning to
      the Netherlands, he was hospitalised with a life-threatening neurologic and multi
      organ failure. It took two weeks before the diagnosis 'Mediterranean spotted
      fever' was made and an appropriate antibiotic treatment was started. The patient
      made a slow but successful recovery. Rereading the hand-written Spanish medical
      report revealed that it had mentioned a correct diagnosis and adequate treatment.
      An apparently safe holiday destination thus does not exclude an imported disease.
      Knowledge of local epidemiology and good communication with the locally consulted
      medical system are essential for a correct diagnosis and therefore for
      appropriate treatment and a good prognosis.

PMID- 14964020
TI  - [Nobel Prize for physiology or medicine in 2003 awarded to the fathers of
      magnetic resonance imaging].
AB  - The 2003 Nobel Prize for Physiology or Medicine has been awarded to the American
      physical chemist Paul Lauterbur (1929) and the British physicist Peter Mansfield
      (1933) for their discoveries in the field of magnetic resonance imaging (MRI).
      Lauterbur devised a method to encode the nuclear magnetic resonance relaxation
      information in an object spatially and to reproduce it as an image. Mansfield
      succeeded in exciting a slice perpendicular to the gradient direction, which
      enabled him to define a third dimension directly. In addition, he developed
      methods to enhance the speed of imaging. A third scientist, the physician Raymond
      Damadian, although equally a pioneer in the field of MRI, was--disputably--not a
      laureate.

PMID- 14964021
TI  - [Diagnosis and treatment of bronchiectasis].
AB  - Patients with bronchiectasis usually have chronic pulmonary infection with
      secondary obstructive airway disease. This disease has to be distinguished from
      chronic obstructive pulmonary disease (COPD). The diagnosis is established with
      the help of high resolution CT scan of the thorax. Further diagnostic evaluation
      is necessary to identify aetiologic factors. The treatment is complicated and
      involves many aspects: treatment of underlying conditions, recognition of
      exacerbations, boosting of tracheobronchial clearance, treatment of haemoptysis,
      surgical resection of affected lung segments and antibiotic therapy. Antibiotic
      therapy can focus on treatment of exacerbations but chronic suppressive
      antibiotic therapy is also used. Favourable results have been reported for
      maintenance treatment with macrolids as well as anti-inflammatory therapy.

PMID- 14964022
TI  - [Persistent hyperinsulinemic hypoglycemia in infancy: differentiated approach to
      a heterogeneous syndrome].
AB  - Persistent hyperinsulinemic hypoglycaemia in infancy (PHHI) presents a diagnostic
      and therapeutic challenge for the treating physician: increased glucose
      requirements, detectable insulin levels at the point of hypoglycaemia,
      inappropriately low blood levels of free fatty acids and ketone bodies are
      characteristic of this condition. Despite recent developments in understanding
      its pathophysiology, treatment remains difficult and there are many long-term
      complications. Adequate treatment strategies are needed to prevent severe
      neurological damage. As there is a high possibility that hyperinsulinism may only
      be transient, aggressive pharmacological treatment is necessary for 4 to 6 weeks
      before moving on to surgical intervention. In the light of recent knowledge,
      routine subtotal pancreatectomy in children is no longer justifiable. An attempt
      should first be made to differentiate between focal and diffuse hypersecretion of
      insulin by using interventional radiology techniques, notably pancreatic venous
      sampling. This then enables targeted partial pancreatectomy.

PMID- 14964023
TI  - [Meniscus transplantation as an option in case of painful arthrosis following
      meniscectomy].
AB  - The menisci play a role as shock absorbers and distribute the pressure uniformly
      over the joint cartilage. Other functions are: the nutrition of the joint
      cartilage, secondary stability and proprioception. In case of a torn meniscus,
      one should first attempt to suture the meniscus, followed by arthroscopic partial
      meniscectomy if suturing is impossible. In a large proportion of patients,
      arthrosis with pain and loss of function of the knee develops several years after
      the meniscectomy. In order to alleviate the symptoms of such arthrosis, a trial
      of meniscus transplantation was undertaken. In two long-term studies without a
      control group, the results of meniscus transplantation were reasonable. The
      results of medial meniscus transplantation are dependent upon the presence of an
      intact anterior cruciate ligament. The accepted indication for meniscus
      transplantation after meniscectomy is: disabling pain following (sub)total
      meniscectomy in a patient younger than 45-50 years of age with a normal alignment
      and a stable knee joint.

PMID- 14964024
TI  - [Diagnostic image (172). A man with blisters after the use of a cold pack.
      Cryotrauma caused by frozen cold pack].
AB  - A 19-year-old soccer player developed cryotrauma after the prolonged application
      of a cold pack to a sprained ankle.

PMID- 14964025
TI  - [No improvement of disciplinary jurisprudence since the implementation of the
      Individual Health Care Professions Act (IHCP Act)].
AB  - OBJECTIVE: To compare the number and nature of the complaints, the complainants,
      the accused health professionals and the sanctions imposed by the disciplinary
      boards before and after the Individual Health Care Professions Act (IHCP Act)
      came into effect at the end of 1997. DESIGN: Descriptive, retrospective. METHOD:
      The authors examined all 4980 verdicts pronounced by the disciplinary boards in
      the first instance during the period 1995-1997 (before the IHCP Act) and then
      during the period 1999-2001 (after the IHCP Act), together with the resulting
      appeal procedures involving physicians, dentists, pharmacists and midwives. The
      following were noted: the year of the verdict, the number and nature of the
      complaints, the types of complainants, the categories of professionals accused,
      the nature of the verdicts, and the number of appeal procedures. RESULTS: During
      the first period, 2453 complaints were brought before the disciplinary board,
      compared to 2527 during the second period. Most of the complaints were made
      against physicians (92% in both periods). The number of complaints that were
      declared to be justified fell from 19% to 15% (p < 0.001). In both periods,
      approximately half of the complaints concerned 'lack of care or inadequate care'
      or 'incorrect treatment', the most frequent verdict was a warning (67% and 72%,
      respectively), and appeals were lodged against almost one-third of the verdicts.
      The number of complaints submitted by the Inspectorate for Health Care decreased
      from 47 to 19. CONCLUSION: In any important aspects, the IHCP Act did not lead to
      improvement in the disciplinary jurisprudence. The decrease in the number of
      complaints that were declared to be justified could be explained by the change in
      composition of the disciplinary boards prescribed by the IHCP Act (more lawyers
      and less fellow professionals). Informing citizens about disciplinary
      jurisprudence and other procedures for lodging complaints may increase the number
      of justified complaints and hence the number of 'justified' verdicts. There is a
      need for further clarification of the tasks and responsibility of the
      Inspectorate for Health Care in case of complaints to the disciplinary boards.

PMID- 14964026
TI  - [Congenital hyperinsulinism in 15 infants, 1981-1999; experiences and new
      insights].
AB  - OBJECTIVE: To report on a retrospective study into the diagnostics and treatment
      of infants with congenital hyperinsulinism (CHI; persistent hyperinsulinemic
      hypoglycaemia). DESIGN: Retrospective and descriptive. METHOD: The study included
      all 15 patients diagnosed with CHI at the St Radboud University Medical Centre,
      the Netherlands, from 1981 until 1999. Data gathered by systematically searching
      case-notes included: presentation, clinical admission, laboratory results,
      treatment and follow-up. RESULTS: Four of the 15 infants were macrosomatic; 12
      (80%) were presented within 4 days of birth, and the rest after the age of 5
      months. Their symptoms were partially aspecific (feeding poorly, lethargy) and
      partially clear, corresponding to neuroglycopaenia (jitteryness, hypotonia). Nine
      infants experienced convulsions. The amount of glucose that had to be
      administered to achieve normoglycaemia (average: 16.9 mg/kg/min) was far above
      the basal requirement of 4-8 mg/kg/min. Ketone serum and free fatty acid values
      were lowered during a hypoglycaemic episode, hyperinsulinism was detected after
      repeated measurements. Five infants responded well to treatment with diazoxide.
      Ten children underwent subtotal pancreatectomy after which 4 remained
      normoglycaemic. Three of the 10 children who underwent surgery developed an
      exocrine pancreas dysfunction. We did not systematically examine
      neuropsychological development, but in 5 of the 15 children this was clearly
      disturbed.

PMID- 14964027
TI  - [Giant diverticulum of the sigmoid].
AB  - A 77-year-old woman who had been examined 8 months previously because of chronic
      abdominal pain and an altered pattern of defecation presented to the emergency
      department with complaints of nausea, vomiting and acute pain in the abdomen. Her
      appetite was diminished and she had lost 10 kg in the past year. The abdominal X
      ray showed a balloon-like, gas-filled intra-abdominal configuration, which proved
      to be a giant diverticulum of the sigmoid. She was treated by resection of the
      diverticulum and the sigmoid. A giant diverticulum is a rare complication of
      diverticulosis, a frequently occurring condition that is encountered most often
      in the sigmoid; the complication can easily be missed. The presenting symptoms
      can vary from an acute abdomen to chronic non-specific abdominal complaints. The
      most important complications of a giant diverticulum are perforation, obstruction
      or a volvulus. In view of the severity of these complications, resection of that
      part of the intestine in which the giant diverticulum arises is the treatment of
      choice.

PMID- 14964028
TI  - [Raised creatine-kinase serum activity: not necessarily a sign of disease].

PMID- 14964029
TI  - [Raised creatine-kinase serum activity: not necessarily a sign of disease].

PMID- 14964030
TI  - [Raised creatine-kinase serum activity: not necessarily a sign of disease].

PMID- 14964031
TI  - [Raised creatine-kinase serum activity: not necessarily a sign of disease].

PMID- 14964032
TI  - [The practice guideline'Pregnancy and puerperium' (first revision) from the Dutch
      College of General Practitioners; a response from the perspective of
      gynaecology].

PMID- 14964033
TI  - [Evaluation and validation of a perinatal death audit by means of feedback to the
      caregivers].

PMID- 14964034
TI  - Financing to Global Fund slashed by the Bush administration.

PMID- 14964035
TI  - New classifications and concepts of pathogenesis and management of diffuse
      interstitial lung diseases.
AB  - The diffuse interstitial lung diseases (ILD) are a very complex group of
      disorders, of which more than 200 specific disease entities are known. All ILD
      are characterized by a homogenous or heterogenous affection of the lung
      parenchyma. In recent years there was a renewed interest in the ILD because new
      concepts have been developed on aetiologic influences, on pathogenetic mechanisms
      (of inflammation versus active fibrosis) and on genetic susceptibility and
      consequently on the diagnostic-therapeutic management. Yet, there remain many
      questions still, e.g. concerning the exact incidence and prevalence of the
      majority of these diseases and concerning the genetic aspects. More specifically
      much research has been carried out on the important group of "idiopathic
      interstitial pneumonias" (IIP) and in particular on "idiopathic pulmonary
      fibrosis" (IPF). Recently several international consensus reports have been
      published with guidelines on the histologic and clinical definitions and on the
      classification and the diagnostic-therapeutic management.

PMID- 14964036
TI  - [Diffuse interstitial lung disorders in systemic diseases].
AB  - Diffuse parenchymal lung disorders (DPLD) can develop in a variety of systemic
      disorders. Schematically grouped, these include connective tissue disorders,
      vasculitis, neoplastic disorders, sarcoidosis and a group of inherited or other
      rare miscellaneous disorders. This overview focuses on sarcoidosis, systemic
      sclerosis and Churg Strauss vasculitis. Pulmonary involvement occurs in more than
      90% of all patients with sarcodosis. Grading into 4 stages is based on the chest
      radiograph. Forms characterised by an acute clinical onset or a low grade lung
      involvement have the highest spontaneous remission rate. The cause of sarcoidosis
      remains unknown. The diagnosis therefore is descriptive, based on the combination
      of clinical observations, chest X ray, and the histological documentation of non
      caseating epitheloid granulomas in tissue biopsies. Treatment with steroids is
      only indicated if organ involvement leads to functional impairment. Lung fibrosis
      is the most important complication of both the "limited" and "diffuse cutaneous
      form" of systemic sclerosis, involving 90% of all patients. The histological
      pattern is that of "Usual Interstitial Pneumonia" (UIP) or "Non-specific
      Interstitial Pneumonia" (NSIP). The pathogenesis of the disorder is thought to
      consist of an abnormal, excessive regenerative response to an auto-immune
      mediated lung injury. Churg Strauss vasculitis is characterised by asthma, blood
      eosinophilia and vasculitis of the small vessels. The affected vessels wall shows
      signs of fibrinoid necrosis and are infiltrated by eosinophils. pANCA (anti
      myeloperoxidase) is considered to play a role in the pathogenesis of the disease.
      Concern has risen that CysLT1 receptor antagonists might induce production of
      pANCA. To date, this has not been substantiated.

PMID- 14964037
TI  - [Diffuse interstitial lung disorders caused by the environment and occupation].
AB  - Diffuse interstitial lung diseases caused by exogenous factors can be divided
      into those that arise as a result of a progressive accumulation of (mainly)
      mineral particles in the lung parenchyma, and those that essentially result from
      a particular susceptibility of the host for specific agents. The former category
      consists mainly of silicosis, coal worker's pneumoconiosis and asbestosis, as
      well as other mineral pneumoconioses. The latter category contains extrinsic
      allergic alveolitis, which is mainly caused by the inhalation of bio-aerosols,
      chronic beryllium disease and other sarcoid-like diseases, and hard-metal or
      cobalt lung. Individual susceptibility is based on a genetic tendency for
      becoming immunologically sensitized (demonstrated for beryllium) and/or possibly
      on a poor defense against oxidative stress (probably relevant for cobalt). Recent
      outbreaks of interstitial lung disease resulting from inhalatory exposure to some
      polymers ("Ardystil syndrome" and "flock worker's lung") show that one should
      remain vigilant for the occurrence of novel occupational causes of pulmonary
      disease.

PMID- 14964038
TI  - Deep brain stimulation in treatment refractory obsessive compulsive disorder.
AB  - Obsessive-compulsive disorder is a worldwide psychiatric disorder with a lifetime
      prevalence of 2% and mainly characterized by obsessional ideas and compulsive
      behaviors and rituals. Many patients show improvement under cognitive behavioral
      and/or pharmacological treatment. A minority of patients is refractory to all
      available therapy and may benefit from capsulotomy. This study aims to
      investigate deep brain stimulation (DBS) as a last resort treatment alternative
      to capsulotomy in treatment refractory obsessive-compulsive disorder. Eight
      patients have been implanted bilaterally in the anterior limbs of the internal
      capsules with a quadripolar electrode. This paper presents the results of the
      first 4 operated patients. Acute deep brain stimulation displays an immediate
      improvement of the speech, mood, eye contact and motor function. Chronic deep
      brain stimulation improves significantly the obsessional and compulsive
      symptomatology in three out of the four patients. This study definitely needs
      replication, but the results are promising. Reversible deep brain stimulation may
      improve the symptomatology of treatment refractory OCD patients, without
      significant side effects.

PMID- 14964039
TI  - [Preserving vision in the elderly: a survey to start a quality development
      program in general practice].
AB  - The study examined the rate of patients, who do not follow recommendations for
      routine screening, do not visit physicians for eye-symptoms and when suffering
      from diabetes or glaucoma do not adhere to follow-up. To what extent can primary
      care physicians impact on these deficits of ophthalmologic care? 4918
      consecutive, > or = 40 old patients of 107 primary care physicians of 9 networks
      participated. Of these patients 15% had never, 43% not within the last 3 years,
      consulted an ophthalmologist. 16% were diabetics, 7% had glaucoma and 46% had
      observed subjective eye symptoms. A quarter of these patients turn to their
      primary care physician, when having eye problems. Primary care physicians do not
      frequently suggest routine ophthalmologic controls nor do they use diagnostic
      tools like the Amsler-grid or the Swinging-Flash-Light Test.

PMID- 14964040
TI  - [Standardized counting of particles in the urine: a comparison between flow
      cytometry, cell chamber counting and traditional sediment analysis].
AB  - We compared the number of particles in the urine with flow cytometry and manual
      methods: cell chamber and standardised sediment analysis. The correlation (r)
      between the KOVA-cell chamber and the flow cytometer UF-100 was 0.966 for
      erythrocytes, 0.935 for leukocytes and 0.902 for squamous epithelial cells.
      Similar results were obtained by a standardised preparation of the sediment.
      Today, the estimation of the cell number in the sediment analysis is still
      common. The KOVA cell chamber system is a cheap alternative for microscopy,
      whereas automation with flow cytometry is only used for large laboratories.
      Reference values were established under optimal conditions (erythrocytes <
      14/microliter, leukocytes < 16/microliter) with a cut-off of 20/microliter.

PMID- 14964041
TI  - [A 63-old patient with right-sided hypogastric pain at 6 months after
      appendectomy].

PMID- 14964042
TI  - [From the craftsman to the specialist physician. The professional rise of
      surgeons].

PMID- 14964043
TI  - Countertransference in factitious disorders and Munchausen syndrome.

PMID- 14964044
TI  - Pfizer educational forum conference-Socratic dialogue: the body and mind:
      atypical antipsychotics, physical well-being and compliance. September 22nd, 2003
      Prague, Czech Republic Municipal House, Square of Republic, 111 21 Prague 1 Czech
      Republic.

PMID- 14964045
TI  - Evaluating the effectiveness of Snoezelen on women who have a dementing illness.
AB  - This paper reports on a study using a single case study design with four women
      who were in the moderate to severe stages of dementia. The aims of the study were
      (i) to explore the effectiveness of Snoezelen on women who have a dementing
      illness and to ascertain the short-term effectiveness after treatment has ceased
      and (ii) to explore how older women with a dementing illness responded to
      individual pieces of equipment in the room. The four women were involved in
      Snoezelen sessions twice a week for a period of 4 weeks. Observations were made
      of mood/behavior using the Interact and Interact short rating scales by Baker &
      Dowling (1995). A Likert scale of measurement was applied to each item on the
      rating scales ranging from 5 'nearly all the time' to 1 'not at all' to produce
      quantitative data. The four women's responses to equipment were recorded during
      each Snoezelen session and a Likert scale of measurement was applied to each
      piece of equipment ranging from +3 'strong positive' to -3 'strong negative' to
      produce quantitative data. Detailed accounts of the four women's verbal responses
      were recorded to produce qualitative data and were thematically analysed. All
      data collected was recorded in the form of line graphs. It was concluded that
      there was an overall positive mood/behavior change lasting 30 minutes after the
      end of the Snoezelen session for all patients. However, the benefits of 'before',
      'during' and 'after' Snoezelen sessions showed no increase over the 8 sessions
      indicating that the benefits of the Snoezelen sessions were not long-term. In
      terms of 'response to equipment' this was generally a positive experience. It is
      concluded that the results of this study support the notion that Snoezelen
      environments offer a valuable adjunct to the care of older people with a
      dementing illness.

PMID- 14964046
TI  - Southeast Asian refugee children: self-esteem as a predictor of depression and
      scholastic achievement in the U.S.
AB  - The eruption of conflicts and war in this century has led to new masses of
      refugees and displaced persons. Globally, host countries will continue to
      confront issues of how to ensure the successful adaptation of refugees who
      typically are women and children. The United States received three major waves of
      Southeast Asian (SEA) refugees during the past twenty-five years. One million SEA
      refugees arrived in the past decade; the majority were children and adolescents.
      Today, there is still a lack of understanding surrounding mental health issues
      and their relationship to children's violence experience. We know that SEA
      refugee children suffered violence during the war in Southeast Asia, their escape
      from homelands, in camps of asylum and in the U.S. Although researchers have
      examined the relationship of violence with depression and post-traumatic stress
      disorder in refugee children, the findings have been unclear and sometimes
      conflictual in their relationship to scholastic achievement. In the U.S., healthy
      self-esteem is recognized as an important component of mental health and academic
      success, while low self-esteem is associated with depression and academic
      failure. In general, self-esteem and measures of self-esteem have not been
      studied cross-culturally. The authors report the findings of a measure of self
      esteem, depression and academic achievement in a convenience sample of 237
      Southeast Asian refugee children aged 6 to 17 years of age in the U.S.
      Internationally, nurses who assess the mental health of refugee children and
      design interventions to assist in their adaptation, will want to have an
      understanding of mental health issues cross-culturally.

PMID- 14964047
TI  - Brazil drives efforts to fight hunger and poverty.

PMID- 14964048
TI  - Evidence-based practice: knowledge and attitudes of selected South African dental
      practitioners.

PMID- 14964049
TI  - In vitro human dental enamel erosion by three different wine samples.
AB  - The aim of this study was to investigate the erosive effect of different wine
      samples on the enamel of human permanent teeth. Twenty-one extracted, sound,
      permanent human incisor teeth were imbedded in epoxy resin and seven immersed in
      each of the three different wine samples for 0, 2, 5, 15, 30, 45 and 60 minute
      periods. The Knoop hardness for each tooth at each of the immersed periods was
      determined as a measure of the degree of enamel erosion (demineralisation). The
      main finding was that all three wines eroded enamel (softer enamel) which should
      mainly be due to their very low pH values (3.2, 3.7, 3.8) and high total acid
      content. From the Wilcoxon non-parametric tests it was clear that wine 2 had the
      severest influence on the hardness of the teeth, and the wines differed
      significantly (p < 1%) from 30 minutes onwards. These tests showed that wine 1
      differed significantly from wine 2 from 30 minutes onwards and so did wine 3, but
      wines 1 and 3 did not differ at all (p > 5%). It is concluded that all three wine
      samples were erosive to enamel and it is difficult to predict the relative
      erosion rate of different kinds of wines according to their chemical
      compositions, as this process is most probably governed and affected by a large
      number of a combination of factors. The only reliable way to know the exact
      degree of erosion of a specific wine is by means of a laboratory study. Possible
      ways to decrease the damaging effect of erosion caused by wine are provided.

PMID- 14964050
TI  - Overservicing in dental practice--ethical perspectives.
AB  - Overservicing or the acceptance of unnecessary, inappropriate, excessive or
      fraudulent treatment is regarded as sanctioned lying, cheating or stealing and
      thus constitutes unethical conduct and a breach of the integrity of the
      profession. During the past year the media have repeatedly reported that the
      private sector is bloated with overservicing: one of the most important factors
      contributing to the increasing inflation of health care costs. Overservicing is
      an ethical problem presenting with a conflict situation among the interests of
      the patient, the provider and the funder. For example, since dentists are in a
      position to gain financially from their professional recommendations, they are at
      risk of having a conflict of interest: by overservicing they collect more fees.
      Low medical aid tariffs, delayed payment of benefits, oversupply of dentists,
      decreasing business and the spiralling costs of dental materials and equipment
      are the primary causes of high practice overheads and low cash-flow levels.
      Dentists may seek alternatives such as overservicing or unnecessary treatment to
      generate income and to improve their cash flow and/or profit. The main motives
      for overservicing are economic survival and financial gain. Some dentists may
      overtreat unintentionally due to out-dated treatment philosophies or where
      criteria for diagnosis and effective care are not clear, leading to variation in
      treatment decisions. Some overservicing may be due to patient-initiated demand.
      Dentists are largely unregulated as to the appropriateness or necessity of
      treatment decisions because of their professional status. Society trusts that
      their professionals will put the benefit of those they serve above their own self
      interests. The aim of this review is to provide dentists with some guidance to
      the process of ethical decision making, the ethical principles involved, moral
      rules, and guidelines for professional standard of care. Business considerations
      whether profit, financial gain or economic survival should never justify
      overservicing by the dentist. If the patients' best interests are always
      considered, the profession of dentistry can ethically exist within a business
      structure.

PMID- 14964051
TI  - Encephalotrigeminal angiomatosis.
AB  - We report an unusual case of encephalotrigeminal angiomatosis in which the facial
      and oral angioma was bilateral, and several teeth were congenitally absent. The
      developmental nature of the anomaly is reviewed. Encephalotrigeminal angiomatosis
      is commonly referred to as the Sturge-Weber syndrome, after Sturge and Weber who
      first described this affliction in 1879. The main clinical features of this
      syndrome are 1. venous angiomatosis of the leptomeninges of the cerebral-cortex,
      usually unilaterally 2. ipsilateral facial angiomatosis that often follows in
      outline the distribution of the trigeminal nerve (Fig 1) 3. ipsilateral gyriform
      calcification of the cerebral cortex 4. epileptic convulsions (contralateral
      focus) or other seizures 5. ocular defects (choroidal angioma, glaucoma
      hemianopia) 6. mental retardation 7. contralateral hemiplegia 8. obesity 9. oral
      mucosal and gingival involvement. Other less typical features are 1. association
      with hypomelanosis of 1 to 10 2. leptomeningeal angioma contralateral to the
      facial nevus 3. leptomeningeal angioma without facial vascular naevus 4.
      association with gastro intestinal hemorrhage 5. paranasal sinus enlargement.
      This syndrome that affects males and females equally, is a rare congenital
      disorder, apparently hamartomatous in nature, from persistence of a primitive
      embryonal vascular plexus. During the sixth week of intra-uterine life this
      plexus develops around the cephalic portion of the neural tube and under the
      ectoderm in the region destined to become facial skin. In the Sturge-Weber
      syndrome, the vascular plexus fails to regress, as is normal during the ninth
      week, resulting in angiomatosis of the related tissues. Variation in the degree
      of persistence or regression of the vascular plexus accounts for unilaterality or
      bilaterality of involvement, and also for an incomplete syndrome in which the
      leptomeninges, but not the facial tissues are affected. Leptomeningeal
      angiomatosis is the primary abnormality of encephalotrigeminal angiomatosis, all
      other features of the syndrome probably being secondary to this. Calcification of
      the cortex is a poorly understood phenomenon which may result from stasis of
      blood in the angioma, associated with altered local metabolism. Epilepsy and
      other neurological seizures, and mental retardation are probably, in their turn,
      secondary to the cortical calcification. The most striking clinical feature of
      the Sturge-Weber syndrome is the facial vascular naevus which generally follows
      the distribution of innervation of one or more divisions of the trigeminal nerve,
      whence the term encephalotrigeminal angiomatosis. However, the naevus may be more
      extensive, down the neck and even onto the chest. The oral tissues underlying the
      affected facial tissues are invariably also angiomatous and may be considerably
      enlarged as a result. Alterations in eruption of teeth have also been noted.
      Histologically, affected soft tissues are very vascular, resembling a pyogenic
      granuloma or a capillary, or cavernous hemangioma. Yukna, Cassingham and Carr
      noted that affected bone was partially replaced by a delicate fibrous tissue
      containing thin-walled vascular spaces. Neither inflammatory cells, nor fatty or
      haemopoietic marrow was noted.

PMID- 14964052
TI  - The tongue: structure and function relevant to disease and oral health.
AB  - The tongue (L. lingua; G. glossa) functions as a digestive organ by facilitating
      the movement of food during mastication and assisting swallowing. Other important
      functions include speech and taste. The tongue consists of striated muscle and
      occupies the floor of the mouth. The dorsal mucosal surface consists of
      stratified squamous epithelium, with numerous papillae and taste buds. The
      tongue, a voluntary muscular structure, is attached by a fold, called the
      frenulum, to the floor of the mouth. Typically, between 8 and 12 circumvallate
      papillae are arranged in an inverted V-shape towards the base of the tongue. This
      anatomical review focuses on structure, function relationships and diseases
      affecting the tongue. From a primary oral health care perspective, this overview
      will facilitate the process of differential diagnosis in persons presenting with
      vesiculo-bullous, ulcerative, atrophic and cystic disorders of the tongue.
      Suspicious lesions should be biopsied to rule out carcinoma.

PMID- 14964053
TI  - What happens to the real needy?

PMID- 14964055
TI  - Bleaching of teeth.

PMID- 14964059
TI  - General practitioner's radiology case 16. Acute leukemia.

PMID- 14964060
TI  - How to handle sticky personnel situations.

PMID- 14964061
TI  - How to profit from criticism.

PMID- 14964062
TI  - Long-term care insurance: why it's a "must".

PMID- 14964063
TI  - Parental presence and absence as a behavior management technique.

PMID- 14964064
TI  - The one-year dental visit and caries risk and prevention.

PMID- 14964065
TI  - Fluoride use: a quick guide for dental offices.

PMID- 14964066
TI  - Let's all "give kids a smile"!

PMID- 14964067
TI  - Is there hope for dental ethics? An interview with ethics expert Dr. David Ozar.
      Interview by Michael Maihofer.

PMID- 14964068
TI  - Merging Healthcare Institutions (Bill 25). Good intentions gone awry.

PMID- 14964069
TI  - [A pioneer in the domain of perinatal grief. Interview by Michelle Loslier].

PMID- 14964075
TI  - [The virtual community in heart health practice].

PMID- 14964076
TI  - [Nursing care and female genital mutilations].

PMID- 14964077
TI  - [Gift of organs, gift of life].

PMID- 14964078
TI  - ["Health without smoking": for better clarification].

PMID- 14964079
TI  - WHO confirms human-to-human avian flu transmission.

PMID- 14964080
TI  - Viewpoint: consensus on TMD therapy.

PMID- 14964081
TI  - Gamma knife stereotactic radiosurgery for treatment of trigeminal neuralgia.

PMID- 14964082
TI  - Management of oromandibular dystonia.

PMID- 14964083
TI  - Tuberculosis in Canada: 2002 pre-release.

PMID- 14964084
TI  - Mass immunization campaign launched to protect 15 million children from polio, as
      outbreak in Nigeria spreads across West Africa.

PMID- 14964085
TI  - [Older donors and double renal transplantation].

PMID- 14964086
TI  - [Conditions for the development of a program of reverse transcriptase-polymerase
      chain reaction for molecular staging of prostatic cancer].
AB  - OBJECTIVE: To determine accurately the conditions for the development of tests
      using RT-PCR for PSA in patients with prostate cancer. METHOD: Gen amplification
      of PSA in cultures of the human prostate tumoral cell line LNCaP with RT-PCR
      under hot-start conditions, and verification through enzyme restriction digestion
      of the PCR product. Also, calculation of the PCR test limit of detection through
      serial dilutions of LNCaP cells in peripheral blood mononucleate cells. RESULTS:
      A highly specific, easy to perform, reproducible RT-PCR protocol has been
      developed. The lowest limit of detection reached was 1 PSA synthesising cell per
      10(6) peripheral blood mononucleate cells. CONCLUSIONS: RT-PCR is a highly
      sensitive technique that allows detection of small numbers of PSA producing cells
      in peripheral blood. This experience allows to establish with precision the
      conditions for the development of RT-PCR tests for PSA.

PMID- 14964087
TI  - [Fournier's gangrene: anatomo-clinical features in adults and children. Therapy
      update].
AB  - Fournier's gangrene is a skin infectious-necrotising process in the peri
      neogenital area affecting males, usually in their sixties or seventies. Isolated
      flora from cultures of the necrotic lesion is commonly multi-microbial. In a
      majority of cases both aerobic and anaerobic micro-organisms are found in the
      cultures, Escherichia coli being the most commonly identified germ. Although
      considered in the past an idiopathic condition, in most patients today a
      genitourinary, anorectal or dermal triggering factor can be identified. There are
      a series of systemic host debilitating disorders such as diabetes mellitus,
      chronic alcohol abuse, and malignant neoplasia that are associated to this
      condition and may be considered risk factor to suffer this disease. Fournier's
      gangrene in children show specific bacteriological, pathogenic, clinical,
      therapeutic and prognostic features that distinguish it from that in adults. The
      most extensively accepted management for this condition includes therapy with
      broad-spectrum parenteral antibiotics and early and aggressive surgical
      debridement of the necrotic areas. Mortality continues to be high, ranging
      between 10-80% in the various series. Finally, a group of 7 patients with
      Fournier's gangrene is analyzed (1991-1998) aiming to establish a comparison
      between our results and those seen in recent series.

PMID- 14964088
TI  - [p53 and Ki67 expression in specimens of radical prostatectomy. Relationship with
      clinico-pathologic data and survival].
AB  - OBJECTIVES: Analysis in T1-T2 prostate cancer of the following: a) Whether there
      is a relationship between Ki67 and p53 over-expression, and clinico-pathological
      variables. b) Whether that expression influences on progression free survival.
      MATERIAL AND METHODS: The study included 68 patients diagnosed with T1-T2
      prostate cancer undergoing radical prostatectomy and immunohistochemical testing
      of Ki67 and p53 in the prostatectomy specimen, indicating in each case the
      percentage of stained cells. The study was carried out by: a) Comparison of means
      between percentage groups of stained cells. b) Grouping patients according to
      expression percentage. In Ki67, a comparison is made between those expressing 0
      5% vs > 5%. In p53, those expressing (0%) vs > 1%. Mean follow-up: 20 months;
      median: 16 months. RESULTS: Mean expression of Ki67 is 7.2% (57% cases > 5%). 60%
      do not over-express p53; mean 3.65; only 15% is higher than 5%. There is a
      correlation between Ki67 and p53 (p: 0.002), but not to PSA. Ki67 expression is
      related with a poorer pathological stage (p: 0.07) and greater biochemical
      progression (p: 0.07), and it has a significant influence on progression free
      survival in both the univariate (at three years 76% vs 48%; p: 0.04) and the
      multivariate studies (RR: 5.7; p: 0.005). Over-expression of p53 is not related
      to any clinico-pathological variable, and does not influence progression free
      survival.

PMID- 14964089
TI  - [Ectopic ureter as cause of urinary incontinence in girls].
AB  - Continuous urine dripping together with normal micturition is the classical
      picture of ectopic ureter in girls. During the years 1982 to 1996, eleven girls
      with such abnormality have been treated at our department. The diagnostic work-up
      included: intravenous pyelogram (IP), ultrasonography (US), renal scintiscan,
      cystogram, cystoscopy and/or vaginoscopy, as well as a thorough exam of the
      external genitalia under general anesthesia. Ten girls had a double renal system,
      one of them being bilateral; one girl had simple kidneys with renal ectopia.
      Treatment was heminephrectomy with ureterectomy in 9 cases, ureteroureterostomy
      with preservation of the hemikidney in one case, and nephrectomy with
      ureterectomy in the case with a simple system. Urinary incontinence in girls due
      to ectopic ureter is an uncommon disease. Eigthty-five% of the cases are
      associated to renal duplication. IP is highly sensible to defect renal
      duplication; direct vision of the ectopic ureter meatus, canalization and
      roentgenologic confirmation of the suspected diagnosis are required prior to
      surgery. Heminephrectomy has been the most common treatment; however, early
      diagnosis by means of US will promote more conservative surgical approaches.

PMID- 14964090
TI  - [Percutaneous embolization of non-functioning renal graft as therapeutic
      alternative to surgical transplantectomy].
AB  - OBJECTIVE: To analyze the indications, results and complications of embolisation
      of a non-tolerated, non-functioning renal graft with regards to surgical
      transplantectomy. MATERIAL AND METHODS: Between 1990 and 1998, 55 patients with
      failed renal graft were studied. Patients had undergone either subcapsular
      transplantectomy (23 patients) or percutaneous embolisation of allograft (32
      patients). Mean age in both groups was 40.9 +/- 3.14 and 42 +/- 2.45 years
      respectively. After start of dialysis, the graft was left in situ for an average
      of 10.2 (+/- 11.2) and 9.9 (+/- 6.5) months. Hospital stay, occurrence of
      complications from the technique used, and results were compared. RESULTS: Post
      embolisation syndrome (high temperature for 2 to 5 days) was seen in 59% cases.
      No major complications secondary to embolization were seen, whereas 13%
      subcapsular nephrectomies had complications that required re-operation. Hospital
      stay was shorter (p > 0.005) in embolized patients than in those undergoing
      surgery. Sings and symptoms of intolerance disappears in 84.4% embolizations.
      Results were unsuccessful in 5 grafts (15.6%) undergoing embolisation, which
      resulted in deferred subcapsular transplantectomy. CONCLUSIONS: Long-term,
      embolization shows acceptable control over the signs and symptoms of intolerance
      and involves less morbidity than transplantectomy. Surgery is useful when
      intolerance persists after one or more embolizations. Because of its features of
      safety and effectiveness, embolisation should be a choice treatment in selected
      cases.

PMID- 14964091
TI  - [Computerization of protocols for tumor follow-up].
AB  - OBJECTIVE: Evaluation of the effectiveness of the surveillance tumoral by means
      of computerized protocols. MATERIAL AND METHODOLOGY: We have carried out a
      retrospective study, taking as example the superficial bladder cancer, where we
      have compared the execution of the tumoral surveillance of the computerized
      protocols regarding the conventional ones. RESULTS: It has been demonstrated that
      the execution percentage and the adjustment to the predetermined terms of the
      explorations requested by the facultative are superior in the computerized
      protocols that in the conventional ones. CONCLUSION: The computerization of the
      tumoral protocols is user-friendly, it improves the execution degree and it saves
      time, providing bigger effectiveness and scientific rigor.

PMID- 14964092
TI  - [Cadaver kidney grafts from donors over 60 years of age should be considered as
      suboptimal].
AB  - Considering the scarcity of organs for transplantation, one possible solution is
      the use of grafts from aged donors (over 50 years). We have reviewed our
      experience in the case of kidney transplantation considering the period from 1989
      1994 in order to attain a minimum follow-up of 36 months. We compare three
      groups: donors aged between 50-60 years (n = 32), donors aged over 60 years (n =
      25) and a control group formed by donors of "ideal" ages. The results show that
      kidneys from donors over 60 years evidence, as compared to the control group, a
      higher incidence of acute tubular necrosis (p = 0.032), significantly higher
      blood creatinine levels in all the intervals considered, and a graft survival
      which is 14% less at 12 months and 40% less at 36 months (p = 0.0009). These
      differences are most probably to be attributed to the changes caused in these
      organs by advancing age and by previous pathological situations, as we have not
      detected a higher incidence of immunologic or surgical complications.

PMID- 14964093
TI  - [Renal elimination of contrast after retrograde urethrocystography].
AB  - We describe a case report in which is shown an extensive extravasation of
      contrast media from urethra lumen following a retrograde urethrocystography. It
      is shown filling of cavernous system and, at once, iliac vessels and inferior
      cava. Later X ray plates demonstrates entire collecting system due to the renal
      contrast excretion.

PMID- 14964094
TI  - [Treatment with triamcinolone cetonide (trigon-depot) for stenosis after surgery
      of severe hypospadias].
AB  - Urethral stenosis is, after the fistula, the most frequent complication in
      patients undergoing hypospadias repair. Incidence ranges between 6% and 10%
      depending on the surgical technique. Treatment of this complication with simple
      dilation of the narrowed segment is enough in most cases. However, dilation of
      the stricture may be difficult in patients with severe hypospadias that required
      wide dissection and excision of fibrotic tissue to repair a large deviation and
      also in patients who had previously multiple operations. We report 3 patients
      with severe hypospadias (scrotal and perineal) with history of multiple
      operations for that condition and postoperative urethral stenosis at different
      sites. All patients had periodical dilations for several months without any
      improvement. Surgical treatment was indicated to enlarge the stenotic segment.
      Enlargement was performed using oral mucosa graft in two cases and a local flap
      in the third one. Urethral stricture recurred in all cases very soon after the
      plasty and repeated dilations did not improve the symptoms. In the presence of
      hard scar tissue it was decided to inject triamcinolone DCI acetoide (Trigon
      depot), a long acting steroid, into the segment where the fibrotic narrowing was
      more severe, in an effort to obtain the same results reported in the treatment of
      hypertrophic scars and keloids. All the patients had repeated triamcinolone
      injections of hypertrophic scars and keloids. All the patients had repeated
      triamcinolone injections every 2-3 months. Follow-up ranges between 5 and 20
      months and all of them are free of symptoms.

PMID- 14964095
TI  - [Testicular teratoma and epididymal adrenal choristoma].
AB  - We report a case of mature testicular cystic teratoma in a 28-month old boy. Due
      to the characteristics of the palpation and its partial transillumination, it may
      be confused with a hydrocele. They emphasize on the rarity and benign nature of
      the peculiarities and refer to its prognosis, usually benign, when is diagnosed
      at about 2 years of age, providing that a very careful examination of the
      histological sections rules out the presence of anaplastic cells. A left inguinal
      orchiectomy was performed because it was not possible to establish a line of
      cleavage between the tumor and the normal tissue. The pathologic examination
      revealed a benign lesion. An adrenal choristoma in the caput epididymis was also
      observed. Postoperative course was satisfactory.

PMID- 14964096
TI  - [Posterior urethral fibroepithelial polyp in children].
AB  - A fibroepithelial polyp in the posterior urethra is a uncommon lesion. It is seen
      more frequently in children than in adults. It should be considered whenever an
      infant or a child presents with micturition disorders, particularly in the case
      of urinary retention. Contribution of two cases, both in children 2- and 5-year
      old.

PMID- 14964097
TI  - [Testicular torsion: which suture should be used?].
AB  - We report a case of left testicular torsion four months after a similar
      homolateral case in which we did detorsion and bilateral fixation of both
      testicles. The antecedent orchiopexy was accomplished using 3-0 silk and
      transseptal fixation of the contralateral testicle. A history of bilateral
      orchiopexy should nor interfere with diagnosing torsion in the acute scrotum. We
      recommend the use of nonabsorbable suture material joining the testis to the
      dartos muscle in 3 locations and the contralateral hemiscrotum must be explored.

PMID- 14964098
TI  - [Testicular luxation. Report of a case].
AB  - We report a case of luxation of the testis in a 38-year-old male. The left
      testis, located at the inguinal region, was immediate closed reduction and after
      surgical orchidopexy.

PMID- 14964099
TI  - [Vesico-acetabular fistula following prosthesis migration].
AB  - A rare case is described of vesico-acetabular fistula following acetabulum
      displacement of a hip replacement towards the inner bladder, fourteen years after
      the original insertion of the prosthesis. In all the reviewed literature of we
      have not found a single described case of vesico-acetabular fistula associated
      with displacement towards the bladder interior of a hip prosthesis, which leads
      us to consider this complication an exceptional one.

PMID- 14964100
TI  - [Heart insufficiency].

PMID- 14964101
TI  - [The epidemiology of heart failure from a Danish perspective].

PMID- 14964102
TI  - [Natriuretic cardiac hormones. Clinical use in heart failure].

PMID- 14964103
TI  - [Diagnostic strategy in heart failure].

PMID- 14964104
TI  - [Diagnostic imaging in heart failure].

PMID- 14964105
TI  - [MR imaging in the assessment of the extent of myocardial infarction].

PMID- 14964106
TI  - [Discomfort from cervix after supravaginal abdominal hysterectomy. A
      retrospective study].

PMID- 14964107
TI  - [Menu composition of evening meals increases energy and protein intake in
      patients with low nutritional intake and reduces waste].

PMID- 14964108
TI  - [Combined salmeterol and fluticasone in the treatment of chronic obstructive
      pulmonary disease].

PMID- 14964109
TI  - [Non-vascular pain among patients with varicose veins. Clinical examination and
      treatment].

PMID- 14964110
TI  - [Desmoplastic fibroma of the mandible].

PMID- 14964111
TI  - [Picture of the month: breast cancer].

PMID- 14964112
TI  - [Also acupuncture can be the cause of needlestick-transmitted diseases].

PMID- 14964113
TI  - [Local disinfectants can not prevent infections in the wounds].

PMID- 14964114
TI  - [Guidelines should be based on real knowledge: allergy to ornamental plants is
      mainly a problem for gardeners].

PMID- 14964115
TI  - Inactivation of Mycoplasma species involved in contagious agalactia.
AB  - The suitability of 5 agents for the inactivation of different field strains of
      the four mycoplasma species associated with contagious agalactia syndrome in
      goats, i.e. Mycoplasma agalactiae, Mycoplasma mycoides subsp. mycoides LC,
      Mycoplasma capricolum subsp. capricolum and Mycoplasma putrefaciens, was
      investigated. Immunoprophylaxis of this syndrome is still based on inactivated
      vaccines, which traditionally use formalin as the inactivating agent. Moreover,
      the limited information existing about this type of vaccine is only based on
      assays against Mycoplasma agalactiae. Our results showed that formalin (0.1%, 37
      degrees C during 16 hours) and phenol (0.5%, 24 hours) were effective against all
      species tested. Surprisingly, binary ethileneimine (BEI), a classical virus
      inactivating agent, also proved to be very effective when it was used in a 0.1 M
      concentration over 24 hours. With heat treatment, every species was inactivated
      at 60 degrees C. No satisfying results were obtained with purified saponin. To
      evaluate the harmful effects of each agent on mycoplasmal proteins, a
      representative strain was subjected to an effective inactivation protocol with
      each agent, which was monitored by Western immunoblotting. Immunoblotting was
      performed using sera of animals inoculated with the respective mycoplasma
      species, to compare the effect of all the agents on treated strains with
      untreated strains. The results confirmed that phenol, BEI and to a lesser extent
      also formalin inactivated all species without causing a significant damage while
      heat caused stronger damage on surface proteins. Future in vivo studies should be
      conducted because, as recently shown, the combined use of a suitable inactivant
      and adjuvant could give rise to the induction of certain cytokines and strong
      antibody production of a specific isotype pattern, thus opening ways to develop
      more efficacious inactivated vaccines against contagious agalactia.

PMID- 14964116
TI  - [Airborne microorganisms in animal stables: stability of endotoxins in the
      environment].
AB  - The stability of endotoxins was investigated in potential sources (feed-stuff,
      litter, water, excrements, surface dust) of that air contaminant and in the
      airborne state. No changes in the endotoxic activity were found in materials with
      high dry matter (straw, hay, dried faeces) during 84 days. In manure samples
      stages of increasing and decreasing endotoxic activity were observed. In water a
      continuous decline of the endotoxic activity was found. However this process was
      characterised by half-life periods on a weekly scale. Bacterial degradation seems
      to be responsible for that loss of endotoxic activity.

PMID- 14964117
TI  - [First detection of Kashmir bee virus in Hesse, Germany].
AB  - We gathered dead bees of 56 Hessian bee colonies following a sudden collapse
      during winter 2002/03. Viral RNA was purified from ten dead bees per sample.
      Kashmir bee virus (KBV) was detected by use of a RT-PCR protocol. 13 samples were
      positive for KBV. The PCR amplicon was sequenced. A BLAST GenBank search clearly
      identified the Hessian amplicon as a KBV fragment. Similarities of more than 85%
      were found. Phylogenetic analysis revealed a close genetic relationship of the
      Hessian isolate to an isolate from New Zealand. The Northamerican, the Russian
      and Australian notations listed in GenBank did not cluster round with the Hessian
      isolate. This is the first documented detection of KBV in Middle Europe.

PMID- 14964118
TI  - A possible relationship between viral infection and chromosome damage in breeding
      boars.
AB  - A cytogenetic analysis of peripheral blood lymphocytes was carried out on
      breeding boars (n = 5) on a farm where viral infections (porcine parvovirosis)
      had occurred. Several different types of chromosomal aberrations were observed
      including chromatid breaks (23.60 +/- 2.88%), exchanges (9.60 +/- 8.99%), and
      fragments (4.26 +/- 3.31%). In addition, 2.94 +/- 1.74% of cells in metaphase
      showed pulverization. Cells with multiple aberrations were seen in two of five
      boars. The chromosomal damage in the boars may have been induced by a genotoxic
      agent such as a viral infection, and may also be related to the reproductive
      impairment of the pigs.

PMID- 14964119
TI  - [Passive immunization in neonatal piglets in natural rearing--effects of birth
      order, birth weight, litter size and parity].
AB  - 603 neonatal piglets (German Landrace) were investigated for passive immunization
      affected by birth order, birth weight, litter size and parity. Concentrations of
      immunoglobulins in the blood serum of piglets on the first day of life served as
      measure for passive immunization. Blood samples were drawn at 12, 18 and 24 hours
      post partum. Quantitative measurements of immunoglobulin classes were carried out
      by radial immunodiffusion. There was a significant effect of birth order, because
      of the rapid changes in colostrum composition between onset of birth and the last
      piglet of each litter. The effect of birth weight was only partly significant and
      different for the immunoglobulin classes. There was no significant effect of
      litter size on passive immunization. Parity had a significant positive effect on
      IgG- and IgA-concentrations in sow's colostrum with litter two to six, parity 1
      and 2 lead to highest IgM concentrations in the blood serum of piglets.

PMID- 14964120
TI  - [The occurrence of transmissible spongiform encephalopathies in roe deer
      (Capreolus capreolus), red deer (Cervus elaphus) and chamois (Rupicapra
      rupicapra) in Bavaria].
AB  - Brain samples of 849 free-ranging ruminants (654 roe deer, 189 red deer and 6
      chamois) from Bavaria were examined for TSE. In this respect, detections of
      PrPres were carried out by ELISA technique (BioRad) and immunohistochemistry
      using the monoclonal antibody (mAb) L42. Validation experiments of the ELISA
      technique for the detection of prionprotein from free-ranging ruminants showed
      that the examination of brains of wild ruminants lead to lower extinctions than
      that of bovine brain samples. Due to the fact that brain samples of 2 known CWD
      positive wapitis showed definite positive results, all samples were analysed by
      this test. There were no indications on the occurrence of TSE in any of the
      sample. In addition, immunohistochemical investigations of 10% of all samples did
      not show PrPres. Due to the large number of samples, the prevalence of TSE in
      Bavaria can be quoted under 0.5% for roe deer and under 1.5% for red deer with a
      certainty of 95%.

PMID- 14964121
TI  - [The prevalence of anti-yersinia outer protein antibodies in Bavarian slaughter
      pigs].
AB  - The aim of the present study was to provide current data on the prevalence of
      anti-Yersinia-antibodies in Bavarian slaughtering pigs. The recomBlot Westernblot
      assay based on five recombinantly produced Yersinia Outer Proteins (YopD, YopE,
      YopH, YopM, V-antigen) is well evaluated for the use in the diagnosis of human
      yersiniosis and proved to be also a valuable tool for the detection of porcine
      antibodies. 965 out of 1002 meat juice samples collected in 53 Bavarian pig farms
      contained anti-Yop/V-Ag-antibodies. Only blots with three or more detectable
      signals were considered as positive. On the basis of these results a possible
      previous history of Yersinia infection was detected in 45.4% of the pigs and all
      of the pig farms. The high prevalence of anti-Yersinia-antibodies found in this
      investigation demonstrates the need for further epidemiological surveillance and
      animal studies to assess consumers' endangering.

PMID- 14964122
TI  - Antimicrobial resistance pattern of Salmonella serotypes isolated from apparently
      healthy slaughtered camels (Camelus dromedarius) in eastern Ethiopia.
AB  - A total of 714 samples consisting of faeces, mesenteric lymph nodes, liver,
      spleen, abdominal and diaphragmatic muscles (each 119) were collected from
      November 2001 to April 2002 from apparently healthy slaughtered camels (Camelus
      dromedarius) in eastern Ethiopia. One hundred sixteen (16.2%) Salmonella strains
      belonging to 16 different serovars were isolated. All Salmonella strains isolated
      were examined for antimicrobial resistance to 17 selected antimicrobials. The
      minimum inhibitory concentration (MIC) values were determined by the
      microdilution broth test. Fifty-two (44.8%) of the Salmonella isolates were
      resistant to one or more antimicrobials. Thirty-nine of the 52 (75%) resistant
      Salmonella serovars exhibited multiple resistance to up to eight different
      antimicrobials. Among the serovars tested, S. Typhimurium, S. Heidelberg, S.
      Braenderup and S. Hadar displayed multiple resistance mainly to streptomycin
      (35.3%), spectinomycin (28.4%), sulfamethoxazole (25.0%), ampicillin (24.1%),
      trimethoprim (22.4%), trimethoprim/sulfamethoxazole (18.9%), tetracycline (12.9%)
      and colistin (11.2%). All Salmonella strains tested were susceptible to
      ciprofloxacin, nalidixic acid, gentamicin, kanamycin and neomycin. The present
      study showed the importance of camels as a potential source of single and
      multiple resistant Salmonella strains to different antimicrobials that are also
      used in the public health sector for the treatment of different bacterial
      diseases in Ethiopia.

PMID- 14964123
TI  - Differences in the development of the small intestine between gnotobiotic and
      conventionally bred piglets.
AB  - The effects of age, weaning and breeding conditions on the small intestinal
      morphology and the distribution of immunocompetent cells were investigated. The
      villus height and numbers of CD3+ T-lymphocytes, measured in the duodenum,
      jejunum and ileum, were determined in both the gnotobiotic and conventionally
      bred piglets. The diet of gnotobiotic piglets was composed of milk-replacement
      and feed mixtures. The application of milk replacement was finished on day 28.
      Conventional piglets were fed on sow's milk and feed mixtures. The animals were
      weaned on day 28. Small intestines were collected from 12 conventional and 12
      gnotobiotic piglets slaughtered at the age of 2, 7, 14, 21, 28 and 35 days. The
      morphology results demonstrated that duodenal and ileal villi were significantly
      higher (p < 0.001) in gnotobiotic piglets during the entire period of the
      experiment. However, the weight of conventional piglets was higher during the
      experiment, in some cases significantly (p < 0.05). A marked reduction, in some
      cases significant (p < 0.001, p < 0.01 respectively), of the villi height on day
      7 after the diet change for both groups of animals was recorded. The results
      demonstrate the differences in the gut development between both groups and their
      relationship to the breeding conditions. Nevertheless, the effect of crucial diet
      changes was observed independently of them. The immunohistochemistry results
      showed significantly (p < 0.001, p < 0.01 respectively) higher numbers of CD3+ T
      lymphocytes in the jejunal villi of conventionally bred piglets. Similar results,
      in some cases significant (p < 0.001, p < 0.01 respectively), were also obtained
      from the other parts of the small intestine. These observations confirm reduced
      microorganism exposure under the gnotobiotic conditions.

PMID- 14964124
TI  - [Acute lead poisoning in cows due to feeding of lead contaminated ash residue].
AB  - In a dairy herd of 21 cows which were on pasture during the day at the end of May
      2002, four eight years old cows were suddenly inappetent and showed severe
      diarrhoea consisting of black discolorate feces. A few days after the onset of
      the disease, three affected cows exhibited neurological disorders. These cows
      were admitted to the IInd Medical Clinic of the University for Veterinary
      Medicine in Vienna. Following clinical signs were observed: circulatory weakness,
      anorexia, atony of the rumen, diarrhoea and in accordance with acute lead
      poisoning typical signs of the central nervous system. One cow died and the other
      two animals were euthanized. Results of blood testing were anaemia, basophil
      spotting of erythrocytes, increase of liver enzymes and CK, hypocalcaemia,
      decrease of potassium and phosphate. The cerebrospinal fluid of two cows showed
      increased CK-, LDH- and AST-values. The lead contents of whole blood samples were
      between 0.486 and 0.928 mg/kg, of liver samples 13.3 to 114.4 mg/kg, of kidney
      samples 172.2 to 448 mg/kg and of rumen content 59 mg/kg fresh matter. At
      necropsy, enteritis, liver fluke disease and severe interstitial and alveolar
      pulmonary emphysema were found. Pathohistologically typical ischaemic necrosis of
      neurons predominantly at the tips of the gyri, disseminated petechial hemorrhages
      and moderate diffuse neovascularisation, but no acid-fast intranucleolar
      inclusion bodies in the renal tubules were observed. As causative agent of the
      acute lead poisoning a residue on combustion, taken up by the cows on the
      pasture, was confirmed. The ash residue was formed by combustion of three tires
      which contained 450 g heavy weights of 96.5% lead for wheel balance. The lead
      content of the ash residue was between 2.9 and 28 g/kg dry matter.

PMID- 14964125
TI  - [Analysis of the population structure of the South German coldblood in Bavaria,
      Germany].
AB  - Gene contributions of foreign populations as well as coefficients of inbreeding
      and relationship were calculated in 1918 South German Coldblood horses registered
      in Bavaria in 2003. Based on nearly complete 8-generation-pedigrees (index of
      pedigree completeness: 76%) the mean coefficient of inbreeding was 23%. After
      considering missing pedigree data, the mean coefficient of inbreeding was 3%. The
      rates of inbreeding per generation in the current population amount to about
      0.43% over the last eight generations and to about 0.15% in the forthcoming
      generation. In the total current population, the mean degree of relationship was
      6%. The proportion of purebred South German Coldblood horses in the current
      population is about 43%. As the Noric horse is of same origin as the South German
      Coldblood, these two breeds can be considered as an entity and thus the
      proportion of purebred genes in the current Bavarian South German Coldblood
      population reaches more than 93%. The Suffolk Punch and Thoroughbred Horse were
      the most important contributors to the current South German Coldblood population,
      whereas the Rhenish-German and Black Forest Draught Horse as well as the
      Percheron had neglectable influences. The effective population size in the
      current Bavarian South German Coldblood population is Ne = 332.

PMID- 14964126
TI  - [Development of the population size, contribution of foreign breeds, inbreeding
      and degree of relationships of the entire Hanoverian scenthound population
      registered in the stud book of the kennel club Hirschmann e.V].
AB  - The entire dog population of Hanoveranian Scenthounds registered since the
      foundation of the kennel club Hirschmann in the year 1894 was analysed for the
      development of the inbreeding and relationship coefficient and the contribution
      of Hanoveranian Scenthound population of foreign countries. The analyses were
      performed using all available pedigree information. In the history, the breeding
      of the Hanoveranian Scenthound was difficult because of the low number of
      breeding dogs which was additionally reduced during World War I and II. The mean
      coefficient of inbreeding of the entire German population was 6.35%. From 1950 to
      1990, the mean coefficient of inbreeding increased from 8.3% to 9.7%. In the
      birth years from 1990 to 2002, the mean coefficient of inbreeding decreased
      slightly to 9.2%. The rates of inbreeding decreased since 1950. For the last 8
      generations the increase of the coefficients of inbreeding per generation was
      0.71%. The mean degree of relationship of the entire population was 7.17%,
      whereby values higher than 75% were found. Gene contributions of 8 other European
      stud books for the Hanoveranian Scenthound could be found in the German
      population. Hereby, the Austrian Hanoveranian Scenthounds had the largest impact
      on the German population with 24.4%. The proportion of genes from the German stud
      book amounted to 67%.

PMID- 14964127
TI  - Analysis of relationships between German heavy horse breeds based on pedigree
      information.
AB  - We analysed the relationship coefficients (R) between the four German heavy horse
      breeds South German Coldblood, Rhenish German Draught Horse, Schleswig Draught
      Horse and Black Forest Draught Horse. The relationship coefficient makes it
      possible to ascertain crossbreeding between the breeds over time, or autonomous
      developments of the breeds, respectively. The investigation revealed that the
      relationship coefficients between the German draught horse breeds were very low.
      The mean relationship coefficients between the four German heavy horse breeds
      were largest between the South German Coldblood and Schleswig Draught Horse
      (0.103%), whereas mean relationship coefficients were lowest between the Rhenish
      German and Black Forest Draught Horse (0.001%). The Rhenish German Draught Horse
      showed largest relationship coefficients with the Schleswig Draught Horse
      (0.09%), while the Black Forest Draught Horse was mostly related to the South
      German Coldblood (0.06%). The results reveal the presence of very few common
      progenitors of the breeds. The gene flow between the breeds is primarily due to
      crossbreeding of stallions and, especially, in the Rhenish German Draught Horse
      population breeding with a few mares from other German draught horse breeds.

PMID- 14964128
TI  - Russian mental health problems on the increase. Proposed law changes are likely
      to exacerbate the situation, say psychiatrists.

PMID- 14964129
TI  - [Nursing research receives new impulse].

PMID- 14964130
TI  - [Life with intestinal cancer. A phenomenologic-empirical study].
AB  - The Da-sein of Colorectal Cancer is an empirical-phenomenological study, which
      aimed at describing the experience of having received a diagnosis of colorectal
      cancer and what this means for the person concerned. Heidegger's Ontology of
      Dasein (1993; 1996) was selected as the philosophical frame of reference. In this
      study, dialogues, field notes and a diary were used as methods for data
      collection. Data analysis followed Colaizzi's analytic method as described by
      Haase (1987). Over all, seven patients who had been diagnosed with colorectal
      cancer were followed over a time-span of 13 months. The findings exposed that
      uncertainty, transitoriness, as well as locus of control are highly important in
      individual illness management. Upon receiving a diagnosis of colorectal cancer
      and subsequent therapeutic treatments uncertainty and transitoriness already
      become determining elements. Despite successful completion of the anti-cancer
      therapies, neither uncertainty, nor transitoriness will disappear completely from
      the patients' life. Upon disclosure of a diagnosis of colorectal cancer, the
      person concern defers to an external locus of control. Patients accept decisions
      taken by others or delegate powers of decision making. After completion of the
      anti-cancer therapies, returning to everyday life becomes the top priority. To
      find their own rhythm of life again patients work at regaining an internal locus
      of control. Powers of decision making are retrieved. Through The Da-sein of
      Colorectal Cancer the period directly before and after the disclosure of the
      diagnosis was investigated. The newly acquired knowledge will contribute to a
      better understanding and facilitate care of this patient group.

PMID- 14964131
TI  - [Health education and tuberculosis control around 1900].
AB  - Health education nowadays is considered a nursing task. Traditionally medical
      doctors claimed that this intervention belonged to their field of work. This
      article investigates the role of German nurses in health education around 1900.
      The problem of tuberculosis control serves as an example. For this purpose the
      academic library for the history of science at the Humboldt University, Berlin
      was searched for relevant sources. From the texts found, statements about health
      education and nursing tasks were compared. RESULTS: For the period around 1900
      two different strategies of control can be identified. The sanatorium, which
      beside its therapeutic function was conceived as an educational institute for
      personal hygiene, occupied the central position. Under the guidance of medical
      doctors a lasting attitude change of patients should occur. Contemporary
      criticism, however, doubted the concept's efficiency. As an alternative, a local
      attendance program by means of welfare offices was suggested. Often, these
      institutions provided the sole practicable way of action. Here, the nursing staff
      acted more independently in comparison to the sanatorium under medical direction.
      Health education played a key role in the work of the welfare nurses.

PMID- 14964132
TI  - [Quality of life despite illness. How does diabetes type 2 change quality of life
      of patients and how can it be modified?].
AB  - The research-question, posed in this study, was: How does diabetes type 2 change
      the quality of life of the persons involved and how can this be influenced? As
      these perceptions are subjective a qualitative approach was chosen. The
      interpretations of the persons involved were collected by using both a focus
      group discussion and individual interviews. CONCLUSION: The quality of life of
      the persons with diabetes type 2 questioned in this study, was altered especially
      in the functional health area. The concepts named here, were house-keeping,
      nutrition and mobility. But also the area of spare-time-management with concepts
      as hobbies and holidays, as well as the area of control with the concept of self
      control, were named as being compromised by the illness. Information was
      recognized as a very important influencing factor. Information can positively
      influence the strength of the impact of diabetes type 2 on the quality of life.

PMID- 14964133
TI  - [Effects of nursing insurance on caregiving daughters--the role of professional
      nursing care].
AB  - In view of the demographic development the topic of "Nursing of elderly
      relatives" is gaining more and more importance within nursing research. The
      object of the investigation described in this paper was to assess the measures of
      the Pflegeversicherung [Long Term Care Insurance] with regard to its effects on
      care-giving daughters. This publication assesses one of the questions of the
      study--what part professional services play in the support of care-giving
      daughters. The data was collected by individual biographic-narrative interviews
      in the private household of care-giving daughters. The data was then evaluated
      according to the method of biographical case reconstruction developed by Gabriele
      Rosenthal. This way we were able to gain a deeper insight into the situation of
      care-giving daughters and analyse the consequences of the
      Pflegeversicherungsgesetz [Long Term Care Insurance Law] from an "inner
      perspective". The results of the study point to both the positive effects of the
      Pflegeversicherungsgesetz and its limits. We were able to show that the expansion
      of out patient services leads to an enhanced nursing infrastructure. In view of
      the part that professional nursing services play, however, the biographical
      access also made it clear that the Pflegeversicherung will not lead to far
      reaching changes in nursing arrangements. In spite of Pflegeversicherung
      caregiving relatives still suffer from personal and emotional strain. Also the
      legal requirements are too narrow and allow hardly enough space for the
      consideration of the family environment and the history of life of relationship
      between daughter and mother.

PMID- 14964134
TI  - [Contribution of professional nurses of ambulatory nursing services to home
      nursing care].
AB  - The meaning and understanding of home care is a leading factor in health care
      both nationally and internationally. The implementation of the law on care
      insurance in Germany demonstrates the understanding of home care and shows
      changes in health care policy. This new context of health care delivery
      influences the nursing profession. New challenges arise and changes in nursing
      perspectives are necessary. The presented study focuses on the contribution of
      nurses in home care situations. Its aim is to illuminate and to understand the
      perspective of home care nurses. Grounded Theory approach is used. Altogether,
      nine participants are interviewed. The results show that nurses aim at keeping
      care recipients in a home care situation as long as possible. In order to achieve
      this, the contribution of nurses are not just limited to rediscountable benefits.
      Voluntary interventions such as managing housework and emotional support for care
      recipients are also being rendered. However, these actions depend on several
      factors, such as the relationship between the nurse and the care recipient, the
      home care situation or the professional attitude of the nurse. In this context,
      nurses have to develop strategies to deal with these various tasks. The
      discussion emphasizes the legislative framework of home care in Germany as well
      as factors that influenced the study.

PMID- 14964135
TI  - [Intuitive work. Influencing feelings of residents and patients in inpatient and
      ambulatory geriatric nursing].
AB  - The concept of sentimental work by Strauss and collaborators is presented and
      investigated empirically within the fields of home and out-patient geriatric care
      by means of questionnaires. The results illustrate that sentimental work is an
      important component of nursing work. Differences in the use of distinct types of
      sentimental work are shown. A comparison between sentimental work in home and out
      patient geriatric care reveals similarities as well as typical differences.

PMID- 14964136
TI  - [Safety of medical products in the hospital: case examples and user feedback].

PMID- 14964137
TI  - Surviving the lethal triad of trauma: a case from Kosovo.

PMID- 14964138
TI  - Puellae Porti Magni. 1806.

PMID- 14964139
TI  - RN Medical School at Clevedon.

PMID- 14964140
TI  - A letter to the Times of Malta 11 October 2003 from Colonel Ethelwald Emilius
      Vella MD FRCPath L/RAMC. Painless surgical operations.

PMID- 14964141
TI  - MedSTAR trauma elective Washington DC March/April 2003.

PMID- 14964142
TI  - The Operating Department Practitioner (ODP)--educational and professional
      developments.

PMID- 14964143
TI  - Tight control. The risk-versus-benefit game.

PMID- 14964144
TI  - Fast food & restaurant fare. Domino's.

PMID- 14964145
TI  - Senior pumpers. Some seniors may benefit from pump therapy even more than young
      people do.

PMID- 14964146
TI  - Eva Kasierer: 72-year-old pumper. At age 72, Eva Kasierer mastered the insulin
      pump and now enjoys better diabetes control than ever.

PMID- 14964147
TI  - Winning at losing: a guide to healthy weight loss. The straight dope on weight
      loss drugs.

PMID- 14964148
TI  - Winning at losing: a guide to healthy weight loss. Losing weight: what really
      works. An ongoing study reveals the secrets of people who keep pounds off.

PMID- 14964149
TI  - Winning at losing: a guide to healthy weight loss. Rating the diets. Experts
      weigh in on the pluses and minuses of popular diet plans.

PMID- 14964150
TI  - Winning at losing: a guide to healthy weight loss. Best and worst exercises for
      weight loss. What works and what does not for shedding pounds through physical
      activity.

PMID- 14964151
TI  - Winning at losing: a guide to healthy weight loss. Meal replacements. Used
      correctly, weight-loss shakes and bars can offer nutritious options.

PMID- 14964152
TI  - Winning at losing: a guide to healthy weight loss. Surgery for obesity. Thousands
      have it every year--should you?

PMID- 14964153
TI  - Research profile. Too many fractures in type 2s.

PMID- 14964154
TI  - Just for teens. Dealing with depression.

PMID- 14964155
TI  - Exercise: the healthy alternative to smoking.

PMID- 14964156
TI  - Getting physical.

PMID- 14964157
TI  - Use it or lose it: exercise, diabetes and CVD.

PMID- 14964158
TI  - Healthy eating. Kick it up! Marinades, rubs, and sauces.

PMID- 14964159
TI  - Fast food & restaurant fare. Nutrition tips. On estimating portion sizes.

PMID- 14964160
TI  - Cullinan's world. Cullinan Williams considers himself lucky. Having diabetes
      helped him discover his talents as a speaker and fundraiser.

PMID- 14964161
TI  - Programmable meters. The handy blood glucose meter meets the 21st century.

PMID- 14964162
TI  - Medicare. Glaucoma testing and nutrition therapy now covered.

PMID- 14964163
TI  - Parmigiano-Reggiano: a small amount makes a grand difference.  A sprinkle of
      Parmigiano-Reggiano will add a unique flavor to everything from soup to salad to
      dessert.

PMID- 14964164
TI  - Research profile. Keeping transplanted islets safe.

PMID- 14964165
TI  - Drugs by mail or modem. Do they beat the corner drugstore?

PMID- 14964166
TI  - Fast food & restaurant fare. Burger King.

PMID- 14964167
TI  - Diabetes worsens prostate symptoms.

PMID- 14964168
TI  - Home A1C test on the way.

PMID- 14964169
TI  - Women's health exchange. Balancing yes with no.

PMID- 14964170
TI  - Getting the stress monkey off your back.

PMID- 14964171
TI  - Coping with your diagnosis. If your diagnosis shook you up, you're not alone.
      Here's help.

PMID- 14964172
TI  - Pumps and type 2 diabetes. If you can improve your diabetes control, and if you
      can accommodate yourself to it, the pump might just be the best diabetes therapy
      for you.

PMID- 14964173
TI  - Express lane. Diabetic cooking. Bunches of lunches.

PMID- 14964174
TI  - Express lane. Diabetic cooking. Snack savvy.

PMID- 14964175
TI  - Express lane. Diabetic cooking. Five ingredients, great meals.

PMID- 14964176
TI  - Express lane. Diabetic cooking. Off-the-shelf cooking.

PMID- 14964177
TI  - Express lane. Diabetic cooking. Soup's on!

PMID- 14964178
TI  - Express lane. Diabetic cooking. The chosen frozen.

PMID- 14964179
TI  - Express lane. Diabetic cooking. Vegetarian delights.

PMID- 14964180
TI  - Express lane. Diabetic cooking. Sweet choices.

PMID- 14964181
TI  - Research profile. A tale of two conditions.

PMID- 14964182
TI  - Rediscovering a missing link: The sensory physiologist and comparative
      psychologist Mathilde Hertz (1891-1975).
AB  - Although her work was greatly respected by scholars from both psychology and
      biology, such as Wolfgang Kohler, Max Wertheimer, and Karl von Frisch, the life
      and work of the German sensory physiologist and comparative psychologist Mathilde
      Hearz (1891-1975) have remained relatively obscure until recently. Her research
      represented a combination of biological principles fused with a psychological
      phenomenological perspective. After a prolific career within a short time span,
      Hertz's career came to an abrupt end in 1933, despite the intervention efforts of
      Max Planck. Hertz's personal and professional fates are in many ways
      representative of the field of comparative psychology in Germany prior to the
      middle of the 20th century, both of its history and its demise.

PMID- 14964183
TI  - Medical sexology: biology, pathophysiology, and clinical aspects. Proceedings of
      a meeting on medical sexology. Rome, Italy. November 8-9, 2002.

PMID- 14964184
TI  - Abstracts from the 2nd International Meeting of the International Society of
      Perinatal Obstetricians. Adelaide, Australia. November 10-13, 2002.

PMID- 14964185
TI  - Programming to eliminate health disparities among ethnic minority populations.
      Proceedings of the Second Annual Primary Care Conference. October 31-November 2,
      2002. Atlanta, Georgia, USA.

PMID- 14964187
TI  - India's battle against the tuberculosis-HIV dual epidemic.

PMID- 14964188
TI  - [Standardization and individuation for corneal clinic and eye bank techniques].

PMID- 14964189
TI  - Proceedings of the European Association for the Study of the Liver (EASL)
      International Consensus Conference on Hepatitis B. September 14-16, 2002. Geneva,
      Switzerland.

PMID- 14964190
TI  - [Orbital disease: the importance of increasing awareness among ophthalmologists].

PMID- 14964192
TI  - BIOMED 2002. Proceeds of the 9th International Symposium on Biomedical Science
      and Technology. September 19-22, 2002. Antalya, Turkey.

PMID- 14964191
TI  - [Advances in the treatment of orbital tumor].

PMID- 14964193
TI  - Notification that new names and new combinations have appeared in volume 53, part
      5, of the IJSEM.
AB  - This listing of names published in a previous issue of the IJSEM is provided as a
      service to bacteriology to assist in the recognition of new names and new
      combinations. This procedure was proposed by the Judicial Commission [Minute
      11(ii), Int J Syst Bacteriol 41 (1991), p. 185]. The names given herein are
      listed according to the Rules of priority (i.e. page number and order of valid
      publication of names in the original articles).

PMID- 14964194
TI  - The roleplayer. Through the years, ombudsmen are an ally for long term care.

PMID- 14964195
TI  - Wheels in motion. A history of the wheelchair.

PMID- 14964196
TI  - [Treatment and problem analysis in acute and chronic instabilities of the elbow].

PMID- 14964197
TI  - Histories of associations. American Health Care Association.

PMID- 14964198
TI  - Histories of associations. Assisted Living Federation of America.

PMID- 14964199
TI  - Histories of associations. National Investment Center for the Seniors Housing &
      Care Industries.

PMID- 14964200
TI  - The women of Roe v. Wade.

PMID- 14964202
TI  - Bibliography. Current world literature. Nose and paranasal sinsuses.

PMID- 14964201
TI  - New report--genetics and human behaviour: the ethical context.

PMID- 14964203
TI  - Human Genetics Commission calls for tougher rules on use and storage of genetic
      data.

PMID- 14964204
TI  - Christian Action Research and Education (CARE): declaration on human genetics and
      other new technologies in medicine.

PMID- 14964205
TI  - Posthumous insemination and consent: the continuing, troubling case of Mr and Mrs
      Blood.

PMID- 14964206
TI  - Conflicting definitions of kinship: the challenge for state regulation of donor
      assisted conception.

PMID- 14964207
TI  - Reports on the potential dangers of genetic tests sold direct to the public.

PMID- 14964208
TI  - House of Lords rejects challenge to therapeutic cloning.

PMID- 14964209
TI  - New code of ethics for device industry.

PMID- 14964210
TI  - Court of Appeal allows tissue typing for human embryos under strict conditions.

PMID- 14964211
TI  - Human dignity and legal reactions to reproductive cloning: is the principle too
      vague?

PMID- 14964212
TI  - Searching for the 'natural': the case for the gene 'for' homosexuality.

PMID- 14964213
TI  - The sanctity of life in a brave new world: a manifesto on biotechnology and human
      dignity.

PMID- 14964214
TI  - Taking blue dye out of tube feedings.

PMID- 14964215
TI  - The moral status of the embryo and the protection of its life.

PMID- 14964219
TI  - FAST results: using focused assessment with sonography for trauma.

PMID- 14964220
TI  - Logrolling a patient.

PMID- 14964221
TI  - When your patient is in police custody.

PMID- 14964222
TI  - Watch those power connections!

PMID- 14964223
TI  - Drawing blood through a central venous catheter.

PMID- 14964224
TI  - Herbal remedies: patient beware.

PMID- 14964225
TI  - Shigella.

PMID- 14964226
TI  - How do I care for a patient after PCI?

PMID- 14964227
TI  - Finance issue brief: managed care report cards: year end report-2003.

PMID- 14964228
TI  - Finance issue brief: bans on gag clauses: year end report-2003.
AB  - Forty-eight states prohibit managed care organizations (MCOs) from limiting a
      provider's ability to discuss potential treatment options with patients.

PMID- 14964229
TI  - Proceedings of a general discussion on nanoparticle assemblies. July 14-16, 2003.
      Liverpool, United Kingdom.

PMID- 14964230
TI  - Finance issue brief: insurer liability: year end report-2003.
AB  - When a health plan denies payment for a procedure on grounds that it is not
      medically necessary or when it refuses a physician-ordered referral to a
      specialist, has it crossed the line from making an insurance judgment to
      practicing medicine? If the patient suffers harm as a result of the decision, is
      the plan liable for medical malpractice? Those were questions 35 states
      considered in 1999, and at least 32 states are grappling with this year as they
      seek to respond to physician and patient pressure to curb the power of the
      managed care industry. Traditionally, health insurers have been protected by
      state laws banning "the corporate practice of medicine," which means the
      patient's only recourse is to sue under a "vicarious liability" theory. Now,
      however, lawmakers are debating legislation to extend the scope of malpractice
      liability beyond individual practitioners to insurance carriers and plans
      themselves.

PMID- 14964231
TI  - ECG examinations.

PMID- 14964232
TI  - Finance issue brief: HMO medical directors: year end report-2003.
AB  - Medical directors of managed care organizations have the ultimate responsibility
      of deciding the treatments for which a health plan will pay. Cognizant of
      consumer concerns over the power inherent in the position, states are seeking to
      inject more accountability into the decision-making process. Lawmakers have begun
      to grapple with whether medical directors should be required to hold a medical
      license from the state in which they work and, by extension, whether they should
      be under the jurisdiction of the state medical board.

PMID- 14964233
TI  - Finance issue brief: freedom of choice: year end report-2003.
AB  - Should managed care plans have the ability to limit an individual's "freedom of
      choice" when it comes to selecting a provider? As part of the anti-managed care
      movement of the early 1990s, 22 states enacted freedom of choice laws; the
      majority apply only to pharmacies.

PMID- 14964234
TI  - Finance issue brief: managed care: overview of state actions: year end report
      2003.

PMID- 14964235
TI  - Finance issue brief: continuity of care: year end report-2003.
AB  - When a health care provider leaves or is terminated by a managed care plan, how
      long can patients continue to receive covered treatment from that provider for a
      life-threatening condition, pregnancy, disability or other circumstance that
      requires continuous medical care? Lawmakers in 36 states have answered that
      question.

PMID- 14964236
TI  - Finance issue brief: medical necessity: year end report-2003.
AB  - The information in this issue brief is based on a 50--state survey and a recent
      literature review. The Health Policy Tracking Service recognizes the complexity
      of this issue and discourages the use of this document as a sole resource on the
      issue.

PMID- 14964237
TI  - Misplaced kindness.

PMID- 14964238
TI  - Finance issue brief: long-term care insurance: year end report-2003.
AB  - A 1996 federal law made it more attractive for states to consider long-term care
      insurance, and states have responded by implementing policies to make the
      purchase of these long-term care coverage more affordable and consumer-friendly.
      At present, policymakers continue to debate the future role of private long-term
      care insurance in subsidizing the increasing demand for long-term care services.

PMID- 14964239
TI  - You routinely administer combination drugs...

PMID- 14964240
TI  - Providers issue brief: nursing shortages: year end report-2003.
AB  - According to a U.S. Department of Health and Human Services report released in
      July of 2002, the national supply of full time equivalent nurses was estimated at
      1.89 million in the year 2000, while the demand was estimated at two million.
      This reflects a nursing shortage of 110,000 or 6 percent. By the year 2015 the
      demand will accelerate and almost quadruple to 20 percent.

PMID- 14964241
TI  - Providers issue brief: alternative and complementary providers: year end report
      2003.

PMID- 14964242
TI  - Providers issue brief: nursing home liability insurance: year end report-2003.
AB  - States have been plagued in recent years by dramatic increases in nursing home
      liability insurance premiums and the flights of insurance carriers. This has
      forced many nursing homes to operate with substandard levels of coverage or
      sometimes no coverage at all. As this crisis worsens, many states are taking
      action to protect both nursing home providers and residents.

PMID- 14964243
TI  - Providers issue brief: end of life issues: year end report-2003.
AB  - Assisted suicide has emerged as one of the most controversial ethical issues in
      the medical community, and one that is complicated more by technological advances
      that have allowed people to live longer. But as policymakers debate assisted
      suicide policy, state lawmakers must also examine ways to improve pain management
      and end-of-life care for people who suffer from terminal illnesses.

PMID- 14964244
TI  - Providers issue brief: tobacco: youth access to tobacco: year end report-2003.
AB  - The use of tobacco products by adolescents concerns advocacy organizations, state
      departments of public health, state legislatures and tobacco manufacturers.
      Research conducted by the Centers for Disease Control and Prevention concludes
      that more than half of all smokers begin smoking before the age of 14, and 90
      percent begin by age 19. The average age of first use is between age 13 and age
      14. The earlier adolescents use tobacco, the more likely they are to use it as
      adults and the longer potential time they have to become habitual users. Both the
      duration and the amount of tobacco use are related to eventual chronic health
      problems, and these chronic health problems add to the states' medical costs. For
      instance, the treatment of tobacco-related illnesses collectively cost the states
      $50 billion to $75 billion annually

PMID- 14964245
TI  - Providers issue brief: change in nonprofit entities: year end report-2003.
AB  - Heightened competition in the health care industry has prompted a growing number
      of nonprofit hospitals to merge with or sell to for-profit firms, in the hope of
      alleviating their financial concerns. The conversion trend, which has many public
      officials concerned about the fate of the charitable assets and care to indigent
      population that nonprofit hospitals have traditionally provided the communities
      in which they are located, has, in turn, led to an overall decline in the number
      of hospitals still in business. To protect the public's investment and ensure
      continued access to care, a growing number of states are thus exploring
      legislation that would open the conversion process to the public; strengthen
      oversight authority, typically through the attorney general; and make certain
      that the proceeds from such transactions are used appropriately.

PMID- 14964246
TI  - Providers issue brief: medical errors and patient safety: year end report-2003.

PMID- 14964247
TI  - Finance issue brief: point of service: year end report-2003.
AB  - A point-of-service (POS) option is a type of plan offered by managed care
      organizations (MCOs), including health maintenance organizations (HMOs), that
      allows people who are willing to pay higher out-of-pocket costs to see out-of
      plan providers. Mandating a point-of-service option essentially eliminates the
      use of closed-panel HMOs. This issue brief addresses only bills that mandate
      managed care plans to offer a point-of-service option.

PMID- 14964248
TI  - Providers issue brief: certificate of need: year end report-2003.
AB  - At one time, every state was required by the federal government to have a
      certificate of need (CON) program. The process was intended to keep down costs
      associated with the construction of new health facilities in the state, and
      prevent over development. When the federal requirement was lifted, however, a
      number of states did away with their programs. Some later restored them in some
      form, and many have kept their programs alive for years, requiring a governmental
      seal of approval for building new facilities such as hospitals and long-term care
      facilities or for acquiring major medical equipment.

PMID- 14964249
TI  - Providers issue brief: tobacco: securitization of tobacco settlement revenue:
      year end report-2003.

PMID- 14964250
TI  - American Dental Education Association 81st Annual Session. March 6-9, 2004,
      Seattle, Washington, USA. Abstracts.

PMID- 14964251
TI  - International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 6th
      Annual European Congress. 9-11 November 2003, Barcelona, Spain. Abstracts.

PMID- 14964252
TI  - United States and Canadian Academy of Pathology 93rd Annual Meeting. March 6-12,
      2004, Vancouver, BC, Canada. Abstracts.

PMID- 14964254
TI  - Bibliography. Current world literature. Asthma.

PMID- 14964253
TI  - Giant pedunculated liposarcoma of the esophagus.

PMID- 14964255
TI  - Abstracts of the 4th Joint Meeting of the German, Austrian and Swiss Society for
      Thoracic and Cardiovascular Surgery. February 15-18, 2004.

PMID- 14964256
TI  - Abstracts of the Irish Society for Rheumatology and Irish Rheumatology Health
      Professional Society Annual General Meeting. 10 October 2003, Dublin.

PMID- 14964257
TI  - Society of Surgical Oncology 57th Annual Cancer Symposium. New York, NY, USA.
      March 18-21, 2004. Abstracts.

PMID- 14964258
TI  - [Abstracts of the 2nd Brain Congress. Paris, France, 14-16, 2004].

PMID- 14964259
TI  - EUROPACE 2003. Abstracts of the Meeting of the European Heart Rhythm Association.
      14-17 December 2003, Paris, France.

PMID- 14964260
TI  - Defining and valuing diversity in EMS.

PMID- 14964261
TI  - SIB 2003. Abstracts of the joint symposia with the British Biochemical Society.
      Ferrara, Italy. September 15-18, 2003.

PMID- 14964262
TI  - Abstracts of the Biophysical Society 48th Annual Meeting. Baltimore, Maryland,
      USA. February 14-18, 2004.

PMID- 14964263
TI  - 2004 Gold Book Buyer's Guide. Company section.

PMID- 14964264
TI  - 2004 Gold Book Buyer's Guide. Product section.

PMID- 14964266
TI  - 2004 Gold Book Buyer's Guide. Government agencies.

PMID- 14964265
TI  - 2004 Gold Book Buyer's Guide. State & province survey.

PMID- 14964267
TI  - [Repercussions of Germinal Law].
AB  - The repression of illegal exercice of pharmacy has always been confronted with
      many difficulties: Drug definition (by law or Courts), access to healthcare,
      economic interests... The role of the profession was always fundamental in the
      actions led to defend monopoly. The birth of Europe of Health and the reinforced
      contribution of State in the Health field should not be neglected for
      justification and size dimension of the monopoly.

PMID- 14964268
TI  - [The title of pharmacist and its prerogatives].
AB  - By creating two access roads to the pharmaceutical profession, the law of
      Germinal was at the origin of the distinction between pharmacists 1st class ans
      pharmacists 2nd class. This distinction only died out at the end of XIXth century
      after having generated and extremely singular type of illegal exercise of
      pharmacy. The litigation yesteryear, based on the prerogatives attached to the
      title of pharmacist, found an echo in contemporary jurisprudence. In order to
      stop the use of the pharmacist's title by graduates working in a para-pharmacy,
      the legislator restricted the use of the title to those graduates exercising the
      pharmaceutical art only.

PMID- 14964269
TI  - [XXV Congress of the Hungarian Oncology Society. Szeged, 12-15 November 2003.
      Abstracts].

PMID- 14964270
TI  - [The creation of the special school of pharmacy of Montpellier].
AB  - The first teaching of the special school of pharmacy of Montpellier began after
      the french revolution when a new law (april, 11, 1803) permited this creation.
      the first building of this school is the old Royal Academy of Medicine in
      downtown Montpellier. The first professors of this school were the city's
      apothicaries. Scientists as A.J. Balard or J.E. Planchon make his fame. In spite
      of difficulties at the beginning of the school creation, it's necessary to praise
      these pioneers in charge of management and pharmacy teaching.

PMID- 14964271
TI  - Laboratorians affect important change.

PMID- 14964273
TI  - Health practitioners' buyer's guide 2004.

PMID- 14964272
TI  - [The creation of the School of Pharmacy of Strasbourg in 1803].
AB  - Several reasons can explain the creation of the School of pharmacy in Strasbourg.
      First the history of the pharmacies which comes back to the XIIIth century and
      that of the pharmacists which were prosperous and often members of council of the
      free city. The first regulation concerning the selling of poisons dates back to
      1400, the one of apothecaries of Strasbourg to about 1500. A detailed regulation
      was published by the City Council in 1675. A Collegium medicum was created. This
      regulation was hardly modified by the French administration which supervised that
      of the city from 1681 on. Several printed books, particularly those on the art of
      distillation or on medicinal plants are amongst the most well known of the
      beginning of the XVIth century. Some pharmaceutical preparations of which the
      celestial theriaca of Strasbourg had also contributed to the renown of Strasbourg
      pharmacists. Finally strategically reasons joint to the existence of a School of
      Medicine School founded in 1794, the First Consul, Napoleon Bonaparte, to create
      the School of Pharmacy of Strasbourg. In spite of the appointment of teachers as
      early as 1803 the School had only a few students and no premises and was
      challenged by the local pharmacists where companions were trained who could
      become pharmacists according to the old system. Its only during the reign of king
      Louis-Philippe that the School developed rapidly.

PMID- 14964274
TI  - New in-room TVs part of service excellence.
AB  - Norwalk (CT) hospital is totally renovating 238 patient rooms to boost
      satisfaction levels. Older TVs and attachments often interfered with bedside
      patient care. New LCD sets do not have to be replaced for 20 years.

PMID- 14964275
TI  - JCAHO and JCR take action to enhance firewall.

PMID- 14964276
TI  - Corrections to 2004 standards, elements of performance.

PMID- 14964277
TI  - Selma Morris awarded 2003 Edwards Medal.

PMID- 14964278
TI  - Bagging DEHP products.

PMID- 14964279
TI  - Mist opportunity.

PMID- 14964281
TI  - Constant coverage of charging and collection concerns.

PMID- 14964287
TI  - Proceedings of the Genetic Analysis Workshop held during the 34th annual meeting
      of the American Society of Human Genetics. Norfolk, Virginia, USA. October 30,
      1983.

PMID- 14964289
TI  - Dynamics of cytokine production in human peripheral blood mononuclear cells
      stimulated by LPS or infected by Borrelia.
AB  - To specify the role of individual cytokines in the immune response to pyrogens,
      isolated and cultivated human peripheral blood mononuclear cells (PBMC) were used
      for the experiments. Different pyrogens (lipopolysaccharide from Escherichia coli
      - LPS and live Borrelia afzelii) were applied and the time course of changes in
      concentrations of different cytokines in the medium was followed using the ELISA
      method. It was found that nonstimulated human PBMC proliferate under in vitro
      conditions and produce IL-6, TNF-alpha, IL-10 and finally also IL-1 beta.
      Productions of IL-12 and INF-gamma are not changed. Proliferation of PBMC is
      potentiated after incubation with LPS or live Borrelia. PBMC stimulated by LPS
      increase the net production (stimulated minus unstimulated) of IL-1 beta and TNF
      alpha significantly, while production of IL-6 was smaller. A delayed increase in
      the production of IL-10 was also observed. Productions of IL-12 and INF-gamma
      were not influenced. In contrast to LPS, stimulation of PBMC with live Borrelia,
      increases also the production of IL-12 and IFN-gamma, besides IL-1 beta, TNF
      alpha, IL-6 and IL-10. Productions of IL-1 beta, IL-6 and TNF alpha increased
      immediately after incubation with both LPS and Borrelia, while productions of IL
      12 and INF-gamma begin to increase 8 hours and production of IL-10 12 hours after
      stimulation. Data indicate that stimulation with different pyrogens may activate
      the cells of the immune cascade in a different way. Stimulation of BPMC by LPS
      seems to activate the initial steps of the immune response (macrophages and
      granulocytes) only, while infection with live Borrelia also stimulates the later
      phase of the immune response, probably due to effect of initially produced
      cytokines.

PMID- 14964290
TI  - Epididymitis associated with abdominal masses (2004:1a).

PMID- 14964291
TI  - "Geometry of the proximal humerus and implications for prosthetic design" by
      Hertel R, et al.

PMID- 14964292
TI  - Current awareness in human psychopharmacology.

PMID- 14964293
TI  - Genetic Analysis Workshop II: summary.
AB  - The second Genetic Analysis Workshop was held October 30, 1983, at the American
      society of Human Genetics meetings in Norfolk, Virginia. Ten groups of
      investigators analyzed three sets of pedigrees generated by computer simulation.
      A summary of the workshop is presented. In this overall description by the
      workshop organizers, the rationale for the choice of problems and the
      characteristics of the three data sets are discussed, and the ten analyses are
      briefly summarized and compared. Following this general summary are brief
      descriptions of the analyses of each group of workshop participants, in
      alphabetical order by senior author.

PMID- 14964294
TI  - Genetic Analysis Workshop II: segregation and three-locus linkage analysis.
AB  - Data stimulated for Genetic Analysis Workshop II were analyzed using PAP.
      Segregation analysis showed a simple recessive mode of inheritance for data set 2
      while no conclusions could be made about the mode of inheritance for data set 3.
      Pairwise linkage analysis suggested three linkage groups, but three-locus
      analysis did not provide strong evidence for the gene order within these groups.
      For three of the four three-locus comparisons performed, three-locus analysis
      suggested the simulated order. In only one case did the pairwise analysis suggest
      the simulated order, indicating the necessity for multi-locus analysis for gene
      order.

PMID- 14964295
TI  - [The foundation of the School of Pharmacy in Paris].
AB  - The Parisian School of Pharmacy originates from the Jardin des apothicaires
      created by the Parisian apothecaries community located rue de l' Arbalete to the
      suburb St Marcel in Paris in the early 17th century. It expenced on this site and
      was successively named the College de pharmacie (1777), the Societe libre des
      pharmaciends de Paris and the Ecole gratuite de pharmacie (1796). The 11 April
      1803 law as well as the government decrees of the same year organised the
      official training education of pharmacists in France with the creation of three
      schools in Montpellier, Paris and Strasbourg. The first director of the Parisian
      School was the well-known Louis-Nicolas Vauquelin. The development of this School
      imposed a new location in Paris, avenue de l' Observatoire, in 1882. The School
      of Pharmacy became Faculte de pharmacie in 1920.

PMID- 14964296
TI  - Paroxetine and the FDA.

PMID- 14964297
TI  - Genetic Analysis Workshop II: results of segregation analyses using POINTER and
      linkage analyses using LIPED.
AB  - Genetic Analysis Workshop II Problems 2 and 3 were analyzed using the segregation
      analysis program, POINTER and the linkage analysis program LIPED. Results of the
      segregation analyses were acceptable with respect to both parameter estimation
      and hypothesis testing. Results of the linkage analyses were also good. Although
      it was noted that the linkage and population association data were sometimes
      compatible with more than one hypothesis, the correct relationships among the
      trait and marker loci were generally among those found compatible with the data.

PMID- 14964298
TI  - [Stent therapy for ihofemoral vein thrombosis and anticoagulant therapy].

PMID- 14964299
TI  - Genetic Analysis Workshop II: study of Problem 2 linkage relationships by
      different methods.
AB  - Segregation and linkage analyse were performed on Problem 2 simulated data.
      Segregation analysis showed evidence for nearly recessive major susceptibility
      locus with parameter estimates close to the simulation input values. Linkage
      between this susceptibility locus (X) and the ten marker loci (A to J) led us to
      propose the following map: X-G-F-B.

PMID- 14964303
TI  - [Brazil's national immunization program: origins and development].
AB  - The article discusses the central aspects of the trajectory of the National
      Immunization Program as regards the dynamics of sectoral policy. Heir to
      successful experiences of the past yet conceived at an entirely different moment,
      the Program followed the triumphant Campaign to Eradicate Smallpox and
      inaugurated a new phase in the history of public policy in the field of
      prevention. Under one sole command, the Program came to articulate a set of
      practices that had previously been spread across a number of government agencies
      and jurisdictions. The article examines the process by which the Program was
      conceived, structured, and developed within government health policy, and also
      underscores the main determinants of this policy, its institutional actors, and
      the political and ideological conflicts born of its implementation, whose success
      was an important component in the structuring of a vaccine market in Brazil.

PMID- 14964306
TI  - Patent paradoxical? 'Public order' and genetic patents.

PMID- 14964307
TI  - The STATs of cancer--new molecular targets come of age.

PMID- 14964308
TI  - Cell adhesion and signalling by cadherins and Ig-CAMs in cancer.

PMID- 14964309
TI  - The SWI/SNF complex--chromatin and cancer.

PMID- 14964310
TI  - Testing guidelines for hereditary non-polyposis colorectal cancer.

PMID- 14964311
TI  - [Vaccination, quality control, and vaccine production in Brazil since 1960].
AB  - The article focuses on the Brazilian government's role in implementation of
      immunization policies and in the emergence of a government structure involving
      production and quality control of immunobiologics. It examines Brazil's National
      Immunization Program, creation of the National Institute for Quality Control in
      Health, and the Program for Self-Sufficiency in Immunobiologics. It also takes a
      general look at the political picture that influences participating actors and at
      changes in Brazil's demographic and epidemiological profile.

PMID- 14964312
TI  - Radiation-induced bystander effects--implications for cancer.

PMID- 14964313
TI  - [New perspectives in viral vaccines].
AB  - New viral vaccines, based on molecular research into genomes and proteins, should
      come into routine use in the coming decades. At the same time, use of different
      immunizing antigens within a single dose is also expected to grow more common,
      with the purpose of reducing the number of vaccinations administered to target
      populations. Given Brazil's scientific and technological importance, the country
      should enhance its participation in the development of new vaccines and in the
      evaluation of their efficacy by involving a larger number of researchers and
      technologists and boosting investment in these activities.

PMID- 14964314
TI  - [Technological development: a weak link in vaccine innovation in Brazil].
AB  - In very recent years, the federal government has launched important initiatives
      mean to strengthen science, technology, and innovation in Brazil and thus enhance
      the results of technological innovation in key areas of the country's economy.
      Yet these initiatives have not been enough to reduce Brazil's heavy dependence on
      goods and technology from more developed nations. The article describes the
      current state of vaccination, production, and technological development of
      vaccines both internationally and nationally. Some thoughts are also offered on
      the complexity of vaccine innovation and the various stages whose completion is
      essential to the whole process of technological development. An analysis is made
      of the parameters and factors involved in each stage; technical requirements for
      facilities and equipment; good manufacturing practice guidelines; organizational,
      infrastructural, and managerial needs; and the lengthy time periods adn high
      costs entailed in these activities.

PMID- 14964315
TI  - [Vaccine innovations in Brazil: recent experiences and structural constraints].
AB  - This contribution to the current discussion on innovations in the area of
      science, technology, and health focuses on two experiences in Brazil's history:
      development of hepatitis B (HB) vaccines and of Hib vaccines against meningitis
      type B (Haemophilus influenzae), produced, respectively, at the Butanta Institute
      and at Bio-Manguinhos, which is the technical -scientific department of Fiocruz
      responsible for industrial production of immunobiologics. The analysis of these
      experiences offers a critical reference point for reflections both on scientific
      and technological development in the area of vaccines as well as on the role of
      leadership and institutional models relied upon to date. This analysis suggests
      that a new science and technology policy should be drawn up, one that would be
      capable of overcoming the barriers of dependence and of responding to the
      challenge of reinforcing local technological skills and know-how as a basic
      source of competitiveness and development in health.

PMID- 14964316
TI  - Computer reconstruction of a human lung boundary model from magnetic resonance
      images.
AB  - A mathematical description of the morphology of the lung is necessary for
      modeling and analyzing the deposition of inhaled aerosols A model of the lung
      boundary was generated from magnetic resonance images, with the goal of creating
      a framework for anatomically realistic morphological models of the human airway
      network. We used data visualization and analysis software to reconstruct the lung
      volume from a series of transverse magnetic resonance images collected at many
      vertical locations in the lung, ranging from apex to base. The lung model was
      then built using isosurface extraction techniques. These modeling methods may
      facilitate the creation of customized morphological models for individual
      subjects, resulting in improved interpretation of aerosol distribution data from
      single-photon-emission computed tomography (SPECT). Such customized models could
      be developed for children and for patients with respiratory diseases, thus aiding
      in the study of inhaled medications and environmental aerosols in these
      populations.

PMID- 14964317
TI  - [Recommendations for the use of iodinated contrast media and for magnetic
      resonance by injection route. Radiological and medico-legal considerations].

PMID- 14964318
TI  - Am I an audiologist?

PMID- 14964319
TI  - Internet application to tele-audiology--"nothin' but net".
AB  - The Telehealth program at East Carolina University has developed a system for
      real-time assessment of auditory thresholds using computer driven control of a
      remote audiometer via the Internet. The present study used 45 adult participants
      in a double-blind study of 2 different systems: a conventional audiometer and an
      audiometer operated remotely via the Internet. The audiometric thresholds
      assessed by these 2 systems varied by no more than 1.3 dB for air conduction and
      1.2 dB for bone conduction. The results demonstrated the feasibility of this new
      "telehearing" audiometric system. With the rapid development of Internet-based
      applications, telehealth has the potential to provide important healthcare
      coverage for rural areas where specialized audiological services are lacking.

PMID- 14964320
TI  - Doctor of Audiology program at the University of Florida.
AB  - The University of Florida on-campus AuD program is described. To date, 63
      students have been enrolled in this program. Sixteen doctoral-level audiology
      faculty teach in this program, either in the classroom or clinically. Coursework
      spans all areas included in the audiology scope of practice. The curriculum also
      has classes taught by faculty in other related disciplines, such as medicine,
      neuroscience, pharmacology, and counseling. Clinical practicum experiences
      throughout the program occur in a major health science center on campus, along
      with a number of other clinical sites. With the support of a large faculty and
      the availability of a wide variety of clinical placements, the University of
      Florida AuD program provides the necessary knowledge and skills for students to
      become autonomous professionals.

PMID- 14964321
TI  - Ball State University's AuD degree.
AB  - This article provides an overview of the AuD degree at Ball State University. In
      1996, Ball State became the third university to offer the AuD. An accompanying
      undergraduate major in preaudiology preparation was established at the same time
      as the AuD, and the nature of the undergraduate program is also summarized.

PMID- 14964322
TI  - Audiological assessment, rehabilitation, and spatial hearing considerations
      associated with visual impairment in adults: an overview.
AB  - The purpose of this paper is to increase awareness and interest among
      audiologists regarding the needs of adults who have both hearing loss and visual
      impairment, particularly people who are blind and travel independently. Case
      history, audiometric testing, and rehabilitation issues are considered, and
      extensive discussion of spatial hearing research as it relates to orientation and
      mobility is provided.

PMID- 14964323
TI  - Predicted gain and functional gain with transcranial routing of signal completely
      in-the-canal hearing aids.
AB  - Transcranial routing of signal (TCROS) was accomplished using completely-in-the
      canal (CIC) hearing aids in 5 profoundly unilaterally hearing-impaired
      individuals. The functional gain realized by the participants far exceeded the
      gain predicted by measuring the acoustic output and real ear aided response of
      the hearing aids. The difference between predicted and functional gain increased
      with signal frequency and was attributed at least in part to mechanical vibration
      of the hearing aid in the external canal. Implications for fitting unilateral
      hearing loss using TCROS amplifying systems are discussed.

PMID- 14964324
TI  - The prediction of hearing loss in persons with cerebral palsy using contralateral
      acoustic reflex threshold for broad-band noise.
AB  - The utility of R. Keith's (1977) method of screening for hearing sensitivity
      using the contralateral acoustic-reflex threshold (ART) for broad-band noise
      (BBN) was tested in persons with cerebral palsy (CP). Three groups of
      participants were included in this prospective study. The first group comprised
      20 normal-hearing individuals without CP whose results were used as normative
      data. The second group comprised 16 participants with normal hearing and CP. The
      third group comprised 22 participants with sensorineural hearing loss and CP. The
      results of this study indicate that Keith's screening method employing ART for
      BBN can be used successfully in a population with multiple handicaps where a
      quick, inexpensive, readily available, and accurate method is needed.

PMID- 14964325
TI  - Effects of noise and reverberation on the precedence effect in listeners with
      normal hearing and impaired hearing.
AB  - The purpose of this study was to determine the effects of reverberation and noise
      on the precedence effect in listeners with hearing loss. Lag burst thresholds
      (LBTs) for 4-ms noise bursts were obtained for 2 groups of participants: impaired
      hearing and normal hearing. Data were collected in reverberant and anechoic
      environments in quiet and noise, at sensation levels of 10, 20, 30, 40, and 50
      dB. Results indicated a significant effect of reverberation on LBTs for both
      participant groups. LBTs increased with sensation level in the reverberant
      environment and decreased with increasing sensation level in the anechoic
      environment. There was no effect of hearing loss on LBTs. When the change in LBT
      due to noise was compared, the effect of noise depended on group and environment,
      with a greater effect of noise on the performance of listeners with impaired
      hearing. It is likely that the ability to fuse direct sounds and early
      reflections is degraded in listeners with impaired hearing and that this
      contributes to the difficulties experienced by these listeners in reverberation
      and noise.

PMID- 14964326
TI  - Evaluating the benefit of speech recoding hearing aids in children.
AB  - Children with significant high-frequency hearing loss may be difficult to fit
      with hearing aids using conventional amplification. Frequency-lowering hearing
      aids using dynamic speech recoding (DSR) technology have been proposed as a
      possible means to achieve full speech audibility. The current study investigated
      78 children from ages 1.3 to 21.6 years (M = 10.6 years) who wore DSR hearing
      aids. These hearing aids provided significant improvements in pure-tone average
      (PTA; mean improvement for the aided versus unaided condition of 49 dB) and high
      frequency PTA (mean improvement for the aided versus unaided condition of 56 dB).
      A subgroup of 19 children were previous users of conventional hearing aids. These
      participants demonstrated a mean improvement of 11 dB in PTA and 12.5% in word
      recognition scores for DSR versus conventional amplification. However, DSR
      hearing aids required repair 3 times as often as conventional hearing aids. The
      greatest benefit was observed in children whose word recognition scores were
      poorest using conventional hearing aids.

PMID- 14964327
TI  - Speech perception benefits from sound field FM amplification.
AB  - The effects of sound field FM amplification (SFA) on speech perception
      performance were investigated in this 2-year study. Kindergarten children with
      normal hearing were randomly assigned to a treatment group, which comprised 7
      classrooms that had SFA systems installed in them, and to a control group, which
      comprised another 7 classrooms that did not have any amplification available. The
      children were followed from the beginning of kindergarten through the end of
      first grade. Improvements in speech perception performance were measured for both
      groups, with the treatment group demonstrating progress much sooner than the
      control group. However, this difference was not apparent by the end of the study.
      The only significant difference measured between the treatment and control groups
      was that the treatment group performed significantly better than the control
      group when the stimuli were presented with SFA for the treatment group and
      without SFA for the control group. The teachers who used SFA enjoyed using
      amplification in their classrooms and felt that their students enjoyed using it
      as well.

PMID- 14964328
TI  - Estimation of hearing loss in children: comparison of auditory steady-state
      response, auditory brainstem response, and behavioral test methods.
AB  - The current pediatric test battery is limited in the severe-to-profound hearing
      loss range by the inability to obtain frequency-specific thresholds. Auditory
      steady-state response (ASSR) is an evoked potential test that can accurately
      measure auditory sensitivity beyond the limits of other test methods. The limited
      amount of clinical research, however, has delayed the acceptance of ASSR into the
      standard pediatric test battery. This study compared thresholds from 76 children
      using ASSR, ABR, and behavioral test methods. Resulting correlations were strong
      and supported the inclusion of ASSR into the standard pediatric test battery.
      ASSR testing provides audiometric information that is essential in the management
      of children with severe-to-profound hearing loss.

PMID- 14964329
TI  - Older adult performance on an altered version of the SSI test.
AB  - The Synthetic Sentence Identification (SSI) test has been used extensively in
      investigations of reduced speech understanding skills in older adults. In this
      study the SSI test was altered by adding noise to the competing message and by
      administering practice lists and equivalent test lists, as well as versions of
      the test that have 4- and 12-s interstimulus intervals (ISIs), along with the
      standard 8-s ISI. The purpose was to determine the effect of these alterations on
      performance in a group of older adults with average pure-tone average 2 values
      less than 33 dB HL. Performance changed as a function of the ISI, with less
      rollover occurring for the 4-s ISI condition than the other 2 ISIs.

PMID- 14964331
TI  - Applying the wisdom of the wolves.

PMID- 14964330
TI  - Chiropractic and dentistry in the 21st Century.

PMID- 14964332
TI  - Why unnamed in Concepts editorial?

PMID- 14964333
TI  - Without prejudice.

PMID- 14964334
TI  - Efficacy of pulsed radio frequency energy therapy in temporomandibular joint pain
      and dysfunction.
AB  - This randomized double-blind study evaluated the effectiveness of pulsed radio
      frequency energy therapy (PRFE) in patients with temporomandibular joint
      arthralgia. Forty subjects (age range 22 to 55 yrs.) were assigned randomly into
      two equal groups: (1) Experimental group received PRFE using the Energex unit
      (Energex, Inc. Emerson, New Jersey) and (2) Control group received PRFE placebo
      treatment using a sham device. Both groups received six applications to the TMJ
      area over two weeks. Data were analyzed for the following times: baseline, first
      and second follow-up visits. Numerical Rating Scale scores for TMJ pain showed a
      significant reduction over time for the experimental group (mean = 6.13 to 3.05,
      p < 0.001). There was also a significant effect for the controls (mean = 5.35 to
      4.20, p = 0.01). The effect for experimental subjects was a mean reduction of
      3.07 versus 1.15 for controls. The significant reduction in controls was
      attributed to the placebo effect. The experimental group showed a significant
      increase in mouth opening (mean = 34.95 to 41.70 mm, p = 0.002), right lateral
      movement (mean = 7.85 to 10.80 mm, p = 0.001) and left lateral movement (mean =
      7.65 to 10.85 mm, p < 0.0001). No significant (p > 0.1) change in the control
      group occurred for mouth opening (mean = 38.50 to 39.65 mm), right lateral
      movement (mean = 8.60 to 8.75 mm) and left lateral movement (mean = 8.50 to 8.80
      mm). No side effects were reported during the treatment and the two week follow
      up. These results suggest strongly that PRFE is a safe and effective treatment
      for TMJ arthralgia as well as for increasing mandibular range of motion.

PMID- 14964335
TI  - Induced oral breathing and craniocervical postural relations: an experimental
      study in healthy young adults.
AB  - The influence of induced oral breathing on head and craniocervical posture was
      studied in ten healthy young adults. After a baseline recording, oral respiration
      was induced by using a swimmer's type nose clip. The subjects were filmed 15 and
      90 minutes after wearing the nose clip, immediately and 15 minutes after taking
      it off. The angles C7-tragion versus the true vertical, nasion-tragion versus the
      vertical, and C7-tragion-nasion were calculated, and the difference between the
      baseline and the four experimental recordings was computed. During the
      experiment, head and neck positions were modified in all subjects, but with a
      large variability for both the direction (flexion or extension) and the extent of
      the modification. Overall, the mean differences were minimal with large standard
      deviations. Differences between baseline and the experimental recordings were
      significant only for the C7-tragion versus the vertical angle (analysis of
      variance, p=0.0083). In conclusion, induced oral respiration may have a
      significant role in the alteration of head and craniocervical posture, but the
      effect was highly variable.

PMID- 14964336
TI  - Cervical lordosis angle measured on lateral cephalograms; findings in skeletal
      class II female subjects with and without TMD: a cross sectional study.
AB  - The literature reports evidence of various types of correlations between cervical
      alterations and cervical pain, and the existence of cervical pain in subjects
      with temporomandibular joint internal derangement (TMD). The hypothesis of this
      study is that cervical lordosis angle (CVT/EVT angle) alteration on
      cephalometrics could be correlated to the presence of TMD. The cephalometric
      records of 50 females with documented TMD were compared with those of a control
      group of 50 females. The subjects in the sample were 25-35 years of age, average
      28.9 years (SD, 3.2). Radiographs were taken in mirror position, and seventeen
      variables, including the CVT/EVT angle, were traced. Double measurements were
      made to evaluate method error using Dahlberg's formula. Pearson's correlation
      coefficient and Mann-Whitney's t-test were used to evaluate the data. Intra-group
      analysis showed significant correlations between the CVT/EVT angle and mandibular
      length (p<0.01), mandibular position (p<0.05), mandibular divergence (p<0.01),
      and overjet (p<0.01) in both groups. Between groups, the analysis showed
      significant differences in CVT/EVT angle (p<0.05), maxillary protrusion (p<0.01),
      mandibular protrusion (p<0.01), mandibular length (p<0.01), mandibular divergence
      (p<0.05), and overbite (p<0.05).

PMID- 14964337
TI  - Changes in bite force and muscle forces in the upper extremities after counter
      irritation.
AB  - Today, physical therapy is recognized as an effective, reversible, and
      conservative treatment for temporomandibular disorders (TMD). The purpose of this
      investigation is to explore the feasibility of utilizing counter irritation with
      ischemic pain at a remote site outside of the head and neck region as a method
      for restoring muscle force in a course of physical therapy. Twenty healthy
      asymptomatic female subjects were recruited for this study. The experiments were
      performed over two days, with the two experimental days randomly assigned to the
      experiment performed with or without counter irritation. The counter irritation
      was applied to the subject's left hand using a submaximal effort tourniquet
      procedure. The maximal bite, finger-pinch, and handgrip forces were measured on
      the right side, and the results from the days with and without the counter
      irritation were compared. As a result, a significantly higher mean maximal bite
      force and a trend toward higher finger-pinch force were observed with the
      irritation than without the irritation, while there was no significant difference
      in the handgrip force. These findings indicate that counter irritation outside of
      the head and neck may be useful for increasing bite force, and may be applicable
      in the treatment of TMD for the restoration of masticatory muscle force.

PMID- 14964338
TI  - A revised view of the dynamics, physiology, and treatment of occlusion: a new
      paradigm.
AB  - A new perspective is proposed regarding the functional dynamics of occlusion, the
      masticatory muscles, and mandibular placement. Each is analyzed on the basis of a
      new criterion: force. Stomatognathic function is represented as an ongoing
      equilibrium maintained between the three-dimensional set of individual occlusal
      forces and the three-dimensional set of bilateral muscle forces. Mandibular
      placement is of prime importance, mediating as it does between the two. The
      conclusion is drawn that occlusion and the muscles can correlate optimally with
      each other only when the mandible occupies its neuromuscular position (NMP),
      herein defined as that placement where muscle accommodation is at its absolute
      minimum. The conclusion is that only the muscles themselves are capable of
      establishing the NMP and that customary conventional technology is inadequate. A
      new technology, hydrostatics, is needed to create the special (not existing
      naturally) occlusal conditions essential to optimally integrating occlusion,
      mandibular placement, and muscles. Preliminary EMG data is offered in support of
      this conclusion.

PMID- 14964339
TI  - A longitudinal study of magnetic resonance (MR) evidence of temporomandibular
      joint (TMJ) fluid in patients with TMJ disorders.
AB  - It has been reported that joint effusion, the excessive accumulation of joint
      fluid in and around the joint, is related to temporomandibular joint (TMJ)
      disorders such as pain and disk displacement. However, there have been no
      longitudinal studies of this phenomenon. We performed a longitudinal study on the
      relationship between joint fluid and various pathological disk conditions. The
      subjects were 17 patients who visited our facility for orthodontic treatment and
      were diagnosed using MRI as having internal derangement of one or both TMJs
      (three males and 14 females; age 12-31 years; mean age 20.5 years). MRI was
      performed before, during, or after treatment for their disorders. We evaluated
      the relationship between changes in joint fluid in the joint space and the state
      of the disk, as well as the presence or absence of pain. Joint fluid was
      evaluated by classifying the extent of high-signal areas in the upper and lower
      articular cavities on T2-weighted images. The extent of high-signal areas was
      classified into five levels. Disk displacement and the extent of displacement
      were evaluated using proton density-weighted images. Statistical analysis was
      performed using the chi-square test, and differences in the distribution among
      the groups were examined. Effusion was noted on the first MRI in nine of the
      eleven joints (81.8%) in which joint fluid decreased on the second MRI (p<0.01).
      Displacement remained unchanged or worsened in 18 of the 21 joints (85.7%) that
      showed joint fluid on the first MRI (p<0.01). Pain was alleviated or absent in
      all joints in which the fluid decreased. These results suggest that joint fluid
      may be a factor in the outcome of disk recapture treatment as well as in the
      evaluation of pain.

PMID- 14964340
TI  - A survey of dentists in the United States regarding a specialty in craniofacial
      pain.
AB  - In an effort to explore whether a specialty for craniofacial pain is warranted,
      the American Academy of Craniofacial Pain (AACP) commissioned an opinion survey
      of dentists. The survey population (N=4000) was stratified by specialty, so that
      dentists in affected areas would be adequately represented: 500 orthodontists and
      dentofacial orthopedists, 500 oral and maxillofacial surgeons, 500 periodontists,
      500 prosthodontists, and 2,000 general practitioners. A total of 930 dentists
      responded for a 23.2% response rate. The survey had multiple purposes: 1. to
      measure the percentage of craniofacial pain patients perceived in dental patient
      populations; 2. to determine whether each dentist prefers to treat the disorder
      or; 3. prefers to refer craniofacial pain patients to clinicians specializing in
      the disorder; and 4. whether dentists favor/oppose the formation of a
      craniofacial pain specialty. The respondents' perception of the prevalence of
      craniofacial pain among their patients was 13.9%. A majority of the responding
      dentists, 54.7%, are in favor of a craniofacial pain specialty. Overall, 65% of
      dentists treat craniofacial pain patients, although more than half, 55%, of all
      dentists also refer such patients. Even 43.6% of dentists who regularly treat
      craniofacial pain favor a specialty, while 76% of those who do not treat such
      patients favor the specialty. The data presented here advocate development of a
      dental specialty in craniofacial pain.

PMID- 14964341
TI  - Three-dimensional reconstruction of TMJ MR images: a technical note and case
      report.
AB  - MR images of the temporomandibular joint at occlusion and at various stages of
      mouth opening were registered and reconstructed three-dimensionally before and
      after a modified condylotomy in a patient with painful disk displacement.
      Following the condylotomy, the condyle/disk relationship had become normalized in
      all three planes of space at closed mouth and during mouth opening. The post
      operative distances of the condylar and diskal paths had increased when compared
      with the preoperative distances. The three-dimensional visualizing method may,
      besides providing diagnostic advantages, be a valuable tool for qualitative and
      quantitative documentation of the efficiency of different treatment methods for
      normalization of the disk/condyle relationship in patients with TMJ disk
      displacement.

PMID- 14964342
TI  - The aPTT assay as a monitor of heparin anticoagulation efficacy in clinical
      settings.
AB  - Activated partial thromboplastin time (aPTT) and prothrombin time (PT) are 2
      major methods of screening patients for bleeding tendency. Heparin is an
      anticoagulant commonly used for various clinical conditions and will thus affect
      the coagulation profile. The influence of heparin on PT vs aPTT, seldom addressed
      in the past, should be carefully investigated. Prospective data on 35 patients
      who were heparinized for clinically indicated conditions were collected and
      analyzed for the change in PT (dPT) and aPTT (daPTT) at 3 time points after
      treatment, all of which were compared with baseline data checked before therapy.
      Age, sex, and the results of a complete blood count and liver and renal function
      tests were also evaluated for each patient to determine their effects on dPT and
      daPTT. The therapeutic goal of keeping the aPTT within a desirable range was
      achieved in approximately 75% of patients by the last day of heparin therapy.
      Within this range, dPTs were not statistically significant, nor was the effect of
      age, sex, hemoglobin level, serum albumin level, white cell count, platelet
      count, or renal or hepatic function. In patients with thrombosis, dPT was not
      significantly influenced by heparin dose. During an overlap in the periods of
      coumadin and heparin administration, PT was used as a guide for adjusting the
      coumadin dose. The anticoagulant effect, indicated by a PT in the target range,
      would occur primarily secondary to coumadin administration and would make it
      relatively easy to decide when to discontinue heparin.

PMID- 14964343
TI  - Acetylsalicylic acid tablets with glycine improve long-term tolerability in
      antiplatelet drug therapy: results of a noninterventional trial.
AB  - To determine the tolerability of a glycine (Gly)-containing acetylsalicylic acid
      (ASA) preparation (Gly-ASA), investigators selected 1135 patients already
      receiving longterm antiplatelet therapy for a noninterventional trial of Gly-ASA
      50 to 300 mg daily. After an average treatment period of 42.6 days, tolerability
      rating scores and the frequency of 5 gastrointestinal (GI) complaints were
      compared with those reported for any previous treatment, including plain ASA.
      After treatment with Gly-ASA, the mean percentage of patients without GI
      complaints increased more than 2-fold, from 28.2% to 60.6%. Furthermore, the mean
      percentage of patients reporting any GI symptoms as "always" present decreased
      from 8.5% to 0.5%. Gly-ASA tolerability was rated "excellent" or "good" by 98% of
      the patients. In 10 patients (0.9%), Gly-ASA treatment was terminated prematurely
      due to GI intolerance (n=4) and nonmedication-related causes (n=6). With respect
      to long-term treatment compliance, the improved tolerability profile observed
      with this Gly-ASA preparation indicates an important advantage over nonglycine
      containing ASA alternatives.

PMID- 14964344
TI  - Antibacterial activity of the fourth-generation fluoroquinolones gatifloxacin and
      moxifloxacin against ocular pathogens.
AB  - The ideal ophthalmic anti-infective exhibits broad-spectrum activity against gram
      positive, gram-negative, and atypical bacterial species. These pathogens can
      cause potentially blinding infections such as keratitis and endophthalmitis, both
      of which are associated with ophthalmic surgery or traumatic injury. These
      infections often require aggressive antibacterial therapy, preferably with newer
      generations of antibiotics. In this study, minimal inhibitory concentration (MIC)
      values for gatifloxacin and moxifloxacin were determined in vitro against
      bacterial strains that were isolated from suspected cases of bacterial keratitis
      and endophthalmitis. The ocular isolates included 7 gram-positive, 4 gram
      negative, and 3 atypical bacterial species. Gatifloxacin and moxifloxacin
      exhibited similar activity against 6 gram-positive organisms: Staphylococcus
      epidermidis, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus
      pyogenes, Bacillus cereus, and Enterococcus faecalis. MIC90 values for the drugs
      against these isolates ranged from 0.08 mg/mL to 0.57 mg/mL and were comparable
      to previously published values against isolates from patients with systemic
      infections. The MIC90 for gatifloxacin against Streptococcus viridans was 0.22
      mg/mL compared with 0.73 mg/mL for moxifloxacin (P = .011). Among the gram
      negative isolates, the mean MIC90 for gatifloxacin against Pseudomonas aeruginosa
      was 1.28 mg/mL compared with 2.60 mg/ mL for moxifloxacin (P = .023). MIC90
      values for gatifloxacin against Klebsiella pneumoniae and Enterobacter aerogenes
      were one fourth to one fifth the values for moxifloxacin. For the atypicals, the
      MIC90 values for gatifloxacin against Nocardia asteroides and Mycobacterium
      chelonae were one fourth the corresponding values for moxifloxacin. Gatifloxacin
      demonstrated a broad spectrum of activity against several key ocular pathogens
      tested in this study and was at least as effective as moxifloxacin against these
      pathogens.

PMID- 14964345
TI  - Multicenter, randomized, controlled trial of heat-killed Lactobacillus
      acidophilus LB in patients with chronic diarrhea.
AB  - Chronic diarrhea is a common bowel disorder; disturbance of intestinal
      microorganisms may play a role in its pathogenesis. This study assessed the
      clinical efficacy of lyophilized, heat-killed Lactobacillus acidophilus LB versus
      living lactobacilli in the treatment of chronic diarrhea. One hundred thirty
      seven patients with chronic diarrhea were randomly allocated to receive either a
      4-week course of 2 capsules of Lacteol Fort twice a day (Lacteol group, 69
      patients) or a 4-week course of 5 chewable tablets of Lacidophilin three times a
      day (Lacidophilin group, 64 patients). The frequency of stools was recorded
      quantitatively, and semiquantitative parameters such as stool consistency,
      abdominal pain, distention, and feeling of incomplete evacuation were evaluated.
      At the second and fourth week of treatment, mean bowel frequency was
      significantly lower in the Lacteol group than in the Lacidophilin group (1.88 +/-
      1.24 vs 2.64 +/- 1.12, 1.39 +/- 0.92 vs 2.19 +/- 1.05; P<.05). At the end of the
      treatment, the clinical symptoms were markedly improved in the Lacteol group,
      indicating that L. acidophilus LB is more effective than living lactobacilli in
      the treatment of chronic diarrhea.

PMID- 14964346
TI  - Effects of trimetazidine and selenium on high-frequency fatigue in isolated rat
      diaphragm muscle.
AB  - Trimetazidine (TMZ), which has been used in numerous experimental studies, is
      applied nowadays with the aim of reducing myocardial ischemia. The aim of this
      study was to determine the prefatigue and postfatigue contractile characteristics
      associated with the relationship between the force and frequency of contraction
      in muscle. The study was conducted using diaphragm muscle isolated from 40 male
      Wistar rats weighing 230 to 270 g. The rats were divided into 4 groups of 10
      animals each: controls and TMZ-, selenium (Se)-, and TMZ+Se-treated groups. The
      rats in the control group were treated with 2 mL of physiologic serum (SF), those
      in the second group with Se 30 microg/kg in 2mL of SF, those in the third group
      with TMZ 5 mg/kg in 2 mL of SF, and those in the fourth group with a combination
      of TMZ 5 mg/kg + Se 30 microg/kg in 2 mL of SF. All rats were treated twice daily
      for 15 days by means of gastric lavage. The rats were then killed by cervical
      dislocation. The diaphragm muscle bands were removed and placed in an organ bath.
      After a 2-hour thermoregulatory period, muscles were fatigued with 5-ms pulses at
      a frequency of 40 Hz. Force-frequency relationships were studied after the
      application of 10, 50, and 100 Hz and the development of contraction curves.
      Contraction forces for the groups treated with TMZ, Se, and TMZ+Se (16.1 +/- 1.2,
      13.2 +/- 1.3, and 14.9 +/- 1.0 g, respectively) were significantly lower than for
      the control group (17.0 +/- 1.4 g) during the prefatigue period (P<.001).
      Similarly, postfatigue contraction forces for the treated groups (15.7 +/- 1.3,
      8.8 +/- 1.0, and 12.0 +/- 1.4 g, respectively) were significantly lower than for
      the control group (12.4 +/- 1.2 g, P<.001, P<.001, and P<.05, respectively). A
      significant decrease was noted in postfatigue contraction forces and contraction
      and relaxation rates in the Se- and TMZ+Se-treated groups compared with
      prefatigue values (P<.001), but the difference was not significant. Force
      frequency relationships were evaluated at 10, 50, and 100 Hz. The tetanic
      contraction forces for the control, Se-, TMZ-, and TMZ+Se-treated groups at 100
      Hz were 81.3 +/- 5.7, 91.6 +/- 6.8, 65.3 +/- 5.0, and 84.9 +/- 7.5 g,
      respectively. In the TMZ-treated group, a significant increase was observed in
      tetanic contraction forces at 100 Hz compared with controls (P<.001); no
      significant changes were seen in the force-frequency relationships at 10 and 50
      Hz. The decrease in the contraction force in the postfatigue period was prevented
      to a larger extent in the TMZ-treated group than in the TMZ+Se- and Se-treated
      groups.

PMID- 14964347
TI  - Master Amino acid Pattern as sole and total substitute for dietary proteins
      during a weight-loss diet to achieve the body's nitrogen balance equilibrium.
AB  - Results of this multicentric study have shown that by giving Master Amino acid
      Pattern (MAP) as a sole and total substitute of dietary proteins to 500
      overweight participants undergoing the American Nutrition Clinics/Overweight
      Management Program (ANC/OMP), the participants' body nitrogen balance could be
      maintained in equilibrium with essentially no calories (MAP 1 g=0.04 kcal),
      thereby preserving the body's structural and functional proteins, eliminating
      excessive water retention from the interstitial compartment, and preventing the
      sudden weight increase after study conclusion commonly known as the yo-yo effect.
      Study results have shown that the use of MAP, in conjunction with the ANC/OMP
      regimen, has proven to be safe and effective by preventing those adverse effects
      associated with a negative nitrogen balance, such as oversized or flabby tissue,
      stretch marks, the sagging of breast tissue, increased hair loss, faded hair
      color, and fragile or brittle nails. Also prevented were those anomalies commonly
      associated with weight-loss diets, such as hunger, weakness, headache caused by
      ketosis, constipation, and decreased libido. The use of MAP in conjunction with
      the ANC/OMP also allowed for mean weight loss of 2.5 kg (5.5 lb) per week,
      achieved through reduction of excessive fat tissue and elimination of excessive
      water retention from the interstitial compartment.

PMID- 14964348
TI  - Master Amino acid Pattern as substitute for dietary proteins during a weight-loss
      diet to achieve the body's nitrogen balance equilibrium with essentially no
      calories.
AB  - Results of this multicentric study have shown that by giving 10 g (10 tablets) of
      Master Amino acid Pattern (MAP) as a substitute for dietary proteins, once a day,
      to 114 overweight participants undergoing the American Nutrition
      Clinics/Overweight Management Program (ANC/OMP), the participants' nitrogen
      balance could be maintained in equilibrium with essentially no calories (MAP 1
      g=0.04 kcal), thereby preserving the body's structural and functional proteins,
      eliminating excessive water retention from the interstitial compartment, and
      preventing the sudden weight increase after study conclusion commonly known as
      the yo-yo effect. Study results have shown that the use of MAP, in conjunction
      with the ANC/OMP, has proven to be safe and effective by preventing those adverse
      effects associated with a negative nitrogen balance, such as oversized or flabby
      tissue, stretch marks, sagging of breast tissue, increased hair loss, faded hair
      color, and fragile or brittle nails. Also preventing those anomalies commonly
      associated with weight-loss diets, such as hunger, weakness, headache caused by
      ketosis, constipation, or decreased libido, the use of MAP, in conjunction with
      the ANC/OMP, allowed for mean weight loss of 1.4 kg (3 lb) per week.

PMID- 14964349
TI  - Bioavailability of beta-aescin from horse chestnut seed extract: comparative
      clinical studies of two Galenic formulations.
AB  - The bioavailability of beta-aescin--the main active constituent of horse chestnut
      seed extract--in a nonretarded test medication in comparison with that in a
      retarded reference formulation was evaluated in 2 randomized crossover clinical
      trials involving 18 healthy volunteers each. Serum concentration/time curves
      derived under steady-state conditions and pharmacokinetic parameters measured
      during both studies showed no significant difference between absorption rates for
      the retarded versus nonretarded preparation. In the first study, investigators
      found a test-to-reference ratio of 1.06 (90% confidence interval [CI] range: 99
      113) for the area under the curve (AUC; the primary outcome measure). Absorption
      rates were diminished during the night compared with daytime rates for both study
      preparations. In the second study, using AUC and maximum concentration (Cmax) as
      the primary characteristics, investigators analyzed bioavailability based on the
      mean of 2 consecutive daytime periods and obtained estimates of 1.07 for AUC (90%
      CI range: 0.96-1.19) and 1.05 for Cmax (90% CI range: 0.90-1.21). Bioequivalence
      of the test and reference drug preparations was thus established according to the
      Note for Guidance on the Investigation of Bioavailability and Bioequivalence.
      Both treatments were equally well tolerated.

PMID- 14964350
TI  - Permeability of musculoskeletal tissues and scaffolding materials: experimental
      results and theoretical predictions.
AB  - Fluid movement produces a wide range of phenomena in musculoskeletal tissues,
      including streaming potentials, hydrodynamic lubrication, nutrient transport, and
      mechanical signaling, all of which are governed by tissue permeability.
      Permeability is a measurement of the ease with which a fluid passes through a
      material and is described by Darcy's law. An appreciation of the flow-related
      structure-function relationships that have been found for musculoskeletal tissues
      as well as the materials used to engineer substitutes is important for clinicians
      and engineers alike. In addition, fluid transport phenomena is one of the most
      often neglected, but important, aspects of developing functional musculoskeletal
      tissue replacements. Mathematical models provide the means to relate permeability
      to microstructure and enable one to span multiple hierarchical length scales. In
      this article, we have summarized the experimentally determined permeability for a
      range of musculoskeletal tissues. In addition, we have included a summary of the
      microstructural models that are available to relate bulk permeability to
      microstructural flow profiles. These models have the potential to predict
      cellular level fluid shear stresses, nutrient and drug transport, degradation
      kinetics, and the fluid-solid interactions that govern mechanical response.

PMID- 14964351
TI  - Automatic generation of finite element meshes from computed tomography data.
AB  - A major obstacle for a broader adoption of the finite element method (FEM) in
      clinical biomedical applications is the generation of the model, frequently too
      slow for the times imposed by the clinical practice. The algorithms for automatic
      mesh generation have greatly improved, but their adoption by the biomedical
      community is still limited. The aim of this work is to review the principal
      algorithms for automatic mesh generation and to critically discuss them with
      particular reference to their applicability in the biomedical field. Specialized
      literature on numerical methods was reviewed in order to identify the main
      theoretical approaches currently available for automatic mesh generation. Then,
      published methods for the automatic generation of finite element models of organs
      from computed tomography data were reviewed and classified with a proposed
      taxonomy. Each method was reconnected to a theoretical approach described in the
      specialized literature whenever possible. Last, each method was critically
      reviewed with respect to its applicability to the clinical practice. None of the
      methods described satisfy all the requirements in terms of automation,
      generality, accuracy, and robustness imposed by a clinical application. However,
      some of these methods can already be successfully used in various application
      contexts, and a few guidelines are drawn.

PMID- 14964352
TI  - Modeling the human lumbar spine for assessing spinal loads, stability, and risk
      of injury.
AB  - This article provides a critical review of biomechanical modeling approaches used
      to estimate spinal loads, stability, and risk of injury. The complete
      biomechanical analysis of the spine requires a two-stage approach: (1)
      equilibrium analysis for estimating tissue loads, and (2) stability analysis for
      estimating structural tolerance of the spine. For each level of analysis, basic
      principles are reviewed and relevant published models and studies are referenced.
      Throughout the article, implications for lumbar function and dysfunction derived
      from the various modeling methods are presented, and their applications are
      discussed. At the end, future directions for research are identified. Detailed
      descriptions of selected modeling approaches are provided in the appendices.

PMID- 14964353
TI  - Reducing atrazine losses: water quality implications of alternative runoff
      control practices.
AB  - Water quality is being affected by herbicides, some allegedly harmful to human
      health. Under scrutiny is atrazine (1-chloro-3-ethylamino-5-isopropylamino-2,4,6
      triazine), a commonly used herbicide in corn (Zea mays L.) and sorghum [Sorghum
      bicolor (L.) Moench] production. Concentrations of soluble and adsorbed atrazine
      losses sometimes exceed the safe drinking water standard of 3 microg L(-1)
      established by the USEPA. This study assesses the protective implications of
      runoff control structures and alternative crop farming practices to minimize
      atrazine losses. Using a computerized simulation model, APEX, the following four
      practices were the most effective with respect to the average atrazine loss as a
      percent of the amount applied: (i) constructing sediment ponds, 0.09%; (ii)
      establishing grass filter strips, 0.14%; (iii) banding a 25% rate of atrazine,
      0.40%; and (iv) constructing wetlands, 0.45%. Other atrazine runoff management
      options, including adoption of alternative tillage practices such as conservation
      and no-till as well as splitting applications between fall and spring, were
      marginally effective.

PMID- 14964354
TI  - Effects of smelter sulfur dioxide emissions: a spatiotemporal perspective using
      carbon isotopes in tree rings.
AB  - We wanted to test the hypothesis that forest exposure to phytotoxic gases
      indirectly affects their carbon uptake. We estimated that the reduction of
      photosynthesis may have reached 20 to 30% at a site located 9 km (test site) from
      the Horne copper smelter in Rouyn-Noranda, which is a point source of SO2. Twenty
      one spruce trees older than 100 yr were selected from seven sites at various
      distances from the smelter to evaluate conditions prior to and during the periods
      of smelter operation. The carbon isotope results obtained from spruce tree rings
      at our test site reveal an unprecedented and abrupt shift of +4/1000 after the
      onset of smelter operations. This large and permanent shift exceeds natural
      variations in regional pre-smelter series or in the series at a remote control
      site. All trees up to 116 km downwind from the smelter show delta13C positive
      shifts following the onset of operations. There is also a clear inverse
      relationship between the amplitude of the first-order trends and distance from
      the smelter. Those delta13C trends indicate that trees exposed to high levels of
      SO2 decrease their level of CO2 uptake through activation of stomatal closure.
      This is strongly supported by the significant departure of the Rouyn-Noranda
      trends from those measured for trees from non-industrialized areas of the
      Northern Hemisphere, or calculated using global atmospheric conditions.
      Considering the large number of SO2 point sources in North America, our results
      imply that CO2 uptake by the boreal forest in the vicinity of these sources may
      be lower than previously thought.

PMID- 14964355
TI  - Biological degradation and greenhouse gas emissions during pre-storage of liquid
      animal manure.
AB  - Storage of manure makes a significant contribution to global methane (CH4)
      emissions. Anaerobic digestion of pig and cattle manure in biogas reactors before
      outside storage might reduce the potential for CH4 emissions. However, manure pre
      stored at 15 to 20 degrees C in buildings before anaerobic digestion may be a
      significant source of CH4 and could reduce the potential CH4 production in the
      biogas reactor. Degradation of energy-rich organic components in slurry and
      emissions of CH4 and carbon dioxide (CO2) from aerobic and anaerobic degradation
      processes during pre-storage were examined in the laboratory. Newly mixed slurry
      was added to vessels and stored at 15 and 20 degrees C for 100 to 220 d. During
      storage, CH4 and CO2 emissions were measured with a dynamic chamber technique.
      The ratio of decomposition in the subsurface to that at the surface indicated
      that the aerobic surface processes contributed significantly to CO2 emission. The
      measured CH4 emission was used to calculate the methane conversion factor (MCF)
      in relation to storage time and temperature, and the total carbon-C emission was
      used to calculate the decrease in potential CH4 production by anaerobic digestion
      following pre-storage. The results show substantial methane and carbon dioxide
      production from animal manure in an open fed-batch system kept at 15 to 20
      degrees C, even for short storage times, but the influence of temperature was not
      significant at storage times of <30 d. During long-term storage (90 d), a strong
      influence of temperature on the MCF value, especially for pig manure, was
      observed.

PMID- 14964356
TI  - Carbon, nitrogen balances and greenhouse gas emission during cattle feedlot
      manure composting.
AB  - Carbon and N losses reduce the agronomic value of compost and contribute to
      greenhouse gas (GHG) emissions. This study investigated GHG emissions during
      composting of straw-bedded manure (SBM) and wood chip-bedded manure (WBM). For
      SBM, dry matter (DM) loss was 301 kg Mg(-1), total carbon (TC) loss was 174 kg
      Mg(-1), and total nitrogen (TN) loss was 8.3 kg Mg(-1). These correspond to 30.1%
      of initial DM, 52.8% of initial TC, and 41.6% of initial TN. For WBM, DM loss was
      268 kg Mg(-1), TC loss was 154 kg Mg(-1), and TN loss was 1.40 kg Mg(-1),
      corresponding to 26.5, 34.5, and 11.8% of initial amounts. Most C was lost as CO2
      with CH4 accounting for <6%. However, the net contribution to greenhouse gas
      emissions was greater for CH4 since it is 21 times more effective at trapping
      heat than CO2. Nitrous oxide (N2O) emissions were 0.077 kg N Mg(-1) for SBM and
      0.084 kg N Mg(-1) for WBM, accounting for 1 to 6% of total N loss. Total GHG
      emissions as CO2-C equivalent were not significantly different between SBM (368.4
      +/- 18.5 kg Mg(-1)) and WBM (349.2 +/- 24.3 kg Mg(-1)). However, emission of
      368.4 kg C Mg(-1) (CO2-C equivalent) was greater than the initial TC content
      (330.5 kg Mg(-1)) of SBM, raising the question of the net benefits of composting
      on C sequestration. Further study is needed to evaluate the impact of composting
      on overall GHG emissions and C sequestration and to fully investigate livestock
      manure management options.

PMID- 14964357
TI  - Pyrene degradation in forest humus microcosms with or without pine and its
      mycorrhizal fungus.
AB  - The mineralization potential of forest humus and the self-cleaning potential of a
      boreal coniferous forest environment for polycyclic aromatic hydrocarbon (PAH)
      compounds was studied using a model ecosystem of acid forest humus (pH = 3.6) and
      pyrene as the model compound. The matrix was natural humus or humus mixed with
      oil-polluted soil in the presence and absence of Scots pine (Pinus sylvestris L.)
      and its mycorrhizal fungus (Paxillus involutus). The rates of pyrene
      mineralization in the microcosms with humus implants (without pine) were
      initially insignificant but increased from Day 64 onward to 47 microg kg(-1) d(
      1) and further to 144 microg kg(-1) d(-1) after Day 105. In the pine-planted
      humus microcosms the rate of mineralization also increased, reaching 28 microg
      kg(-1) d(-1) after Day 105. The 14CO2 emission was already considerable in
      nonplanted microcosms containing oily soil at Day 21 and the pyrene
      mineralization continued throughout the study. The pyrene was converted to CO2 at
      rates of 0.07 and 0.6 microg kg(-1) d(-1) in the oily-soil implanted microcosms
      with and without pine, respectively. When the probable assimilation of 14CO2 by
      the pine and ground vegetation was taken into account the most efficient
      microcosm mineralized 20% of the 91.2 mg kg(-1) pyrene in 180 d. The presence of
      pine and its mycorrhizal fungus had no statistically significant effect on
      mineralization yields. The rates of pyrene mineralization observed in this study
      for forest humus exceeded the total annual deposition rate of PAHs in southern
      Finland. This indicates that accumulation in forest soil is not to be expected.

PMID- 14964358
TI  - Overexpression of ATP sulfurylase in Indian mustard: effects on tolerance and
      accumulation of twelve metals.
AB  - Indian mustard [Brassica juncea (L.) Czern.] transgenics overexpressing ATP
      sulfurylase (APS plants) were shown previously to have higher levels of total
      thiols, S, and Se. The present study explores the effect of ATP sulfurylase
      overexpression on tolerance and accumulation of other metals, both oxyanions and
      cations, reasoning that some anions may react directly with ATP sulfurylase,
      while other ions may be bound by its thiol end products. The APS transgenics were
      compared with wild-type plants with respect to tolerance and accumulation of As,
      Cd, Cr, Cu, Hg, Mn, Mo, Ni, Pb, V, W, and Zn, supplied individually in agar
      medium (seedlings) or in hydroponics (mature plants). At the seedling stage, APS
      transgenics were more tolerant than wild type to As(III), As(V), Cd, Cu, Hg, and
      Zn, but less tolerant to Mo and V. The APS seedlings had up to 2.5-fold higher
      shoot concentrations of As(III), As(V), Hg, Mo, Pb, and V, and somewhat lower Cr
      levels. Mature APS plants contained up to 2.5-fold higher shoot concentrations of
      Cd, Cr, Cu, Mo, V, and W than wild type. They also contained 1.5- to 2-fold
      higher levels of the essential elements Fe, Mo, and S in most of the treatments.
      Mature APS plants showed no differences in metal tolerance compared with the wild
      type. Overexpression of ATP sulfurylase may be a promising approach to create
      plants with enhanced phytoextraction capacity for mixtures of metals.

PMID- 14964359
TI  - Attenuation of methane and volatile organic compounds in landfill soil covers.
AB  - The potential for natural attenuation of volatile organic compounds (VOCs) in
      landfill covers was investigated in soil microcosms incubated with methane and
      air, simulating the gas composition in landfill soil covers. Soil was sampled at
      Skellingsted Landfill at a location emitting methane. In total, 26 VOCs were
      investigated, including chlorinated methanes, ethanes, ethenes, fluorinated
      hydrocarbons, and aromatic hydrocarbons. The soil showed a high capacity for
      methane oxidation resulting in very high oxidation rates of between 24 and 112
      microg CH4 g(-1) h(-1). All lower chlorinated compounds were shown degradable,
      and the degradation occurred in parallel with the oxidation of methane. In
      general, the degradation rates of the chlorinated aliphatics were inversely
      related to the chlorine to carbon ratios. For example, in batch experiments with
      chlorinated ethylenes, the highest rates were observed for vinyl chloride (VC)
      and lowest rates for trichloroethylene (TCE), while tetrachloroethylene (PCE) was
      not degraded. Maximal oxidation rates for the halogenated aliphatic compounds
      varied between 0.03 and 1.7 microg g(-1) h(-1). Fully halogenated hydrocarbons
      (PCE, tetrachloromethane [TeCM], chlorofluorocarbon [CFC]-11, CFC-12, and CFC
      113) were not degraded in the presence of methane and oxygen. Aromatic
      hydrocarbons were rapidly degraded giving high maximal oxidation rates (0.17-1.4
      microg g(-1) h(-1)). The capacity for methane oxidation was related to the depth
      of oxygen penetration. The methane oxidizers were very active in oxidizing
      methane and the selected trace components down to a depth of 50 cm below the
      surface. Maximal oxidation activity occurred in a zone between 15 and 20 cm below
      the surface, as this depth allowed sufficient supply of both methane and oxygen.
      Mass balance calculations using the maximal oxidation rates obtained demonstrated
      that landfill soil covers have a significant potential for not only methane
      oxidation but also cometabolic degradation of selected volatile organics, thereby
      reducing emissions to the atmosphere.

PMID- 14964360
TI  - Environmental factors influencing attenuation of methane and
      hydrochlorofluorocarbons in landfill cover soils.
AB  - The influence of different environmental factors on methane oxidation and
      degradation of hydrochlorofluorocarbons (HCFCs) was investigated in microcosms
      containing soil sampled at Skellingsted Landfill, Denmark. The soil showed a high
      capacity for methane oxidation resulting in a maximum oxidation rate of 104
      microg CH4 g(-1) h(-1) and a low affinity of methane with a half-saturation
      constant of 2.0% v/v. The hydrochlorofluorocarbons HCFC-21
      (dichlorofluoromethane) and HCFC-22 (chlorodifluoromethane) were rapidly oxidized
      and the oxidation occurred in parallel with the oxidation of methane. The maximal
      HCFC oxidation rates were 0.95 and 0.68 microg g(-1) h(-1) for HCFC-21 and HCFC
      22, respectively. Increasing concentrations of HCFCs resulted in decreased
      methane oxidation rates. However, compared with typical concentrations in
      landfill gas, relatively high HCFC concentrations were needed to obtain a
      significant inhibition of methane oxidation. In general, the environmental
      factors studied influenced the degradation of HCFCs in almost the same way as
      they influenced methane oxidation. Temperature had a strong influence on the
      methanotrophic activity giving high Q10 values of 3.4 to 4.1 over the temperature
      range of 2 to 25 degrees C. Temperature optimum was around 30 degrees C; however,
      oxidation occurred at temperatures as low as 2 degrees C. A moisture content of
      25% w/w yielded the maximum oxidation rate as it allowed good gas transport
      together with sufficient microbial activity. The optimum pH was around neutrality
      (pH = 6.5-7.5) showing that the methanotrophs were optimally adapted to the in
      situ pH, which was 6.9. Copper showed no inhibitory effect when added in
      relatively high concentrations (up to 60 mg kg(-1)), most likely due to sorption
      of copper ions to soil particles. At higher copper concentrations the oxidation
      rates decreased. The oxidation rates for methane, HCFC-21, and HCFC-22 were
      unaltered in ammonium-amended soil up to 14 mg kg(-1). Higher ammonium
      concentrations inhibited the oxidation process. The most important parameters
      controlling oxidation in landfill cover soil were found to be temperature, soil
      moisture, and methane and oxygen supply.

PMID- 14964361
TI  - Sequential supercritical fluid extraction (SSFE) for estimating the availability
      of high molecular weight polycyclic aromatic hydrocarbons in historically
      polluted soils.
AB  - Sequential supercritical fluid (CO2) extraction (SSFE) was applied to eight
      historically contaminated soils from diverse sources with the aim to elucidate
      the sorption-desorption behavior of high molecular weight polycyclic aromatic
      hydrocarbons (PAHs). The method involved five extraction phases applying
      successively harsher conditions by increasing fluid temperature and density
      mobilizing target compounds from different soil particle sites. Two groups of
      soils were identified based on readily desorbing (available) PAH fractions
      obtained under mildest extraction conditions (e.g., readily desorbing fractions
      of fluoranthene and pyrene significantly varied between the soils ranging from
      <10 to >90%). Moreover, extraction behavior strongly correlated with molecular
      weight revealing decreasing available PAH fractions with increasing weight.
      Physicochemical soil parameters such as particle size distribution and organic
      dry mass were found to have no distinct effect on the sorption-desorption
      behavior of PAHs in the different soils. However, PAH profiles significantly
      correlated with readily available pollutant fractions; soils with relatively less
      mobile PAHs had higher proportions of five- and six-ring PAHs and vice versa.
      Eventually, biodegradability corresponded well with PAH recoveries under the two
      mildest extraction phases. However, a quantitative relationship was only
      established for soils with biodegradable PAHs. Out of eight soils, five showed no
      biodegradation including the four soils with the lowest fraction of readily
      desorbing PAHs. Only one soil (which was found to be highly toxic to Vibrio
      fischeri) did not match the overall pattern showing no PAH biodegradability but
      large fractions of highly mobile PAHs, concluding that mass transfer limitations
      may only be one of many factors governing biodegradability of PAHs.

PMID- 14964362
TI  - Leaching of dissolved organic carbon and carbon dioxide emission after compost
      application to six nutrient-depleted forest soils.
AB  - The objective of this study was to assess the effect of compost application on
      soil respiration and dissolved organic carbon (DOC) output of nutrient-depleted
      forest soils. An amount of 6.3 kg m(-2) mature compost was applied to the forest
      floor of European beech (Fagus sylvatica L.), Norway spruce (Picea abies Karst.),
      and Scots pine (Pinus sylvestris L.) stands at Soiling and Unterluss, Germany.
      Cumulative soil respiration significantly increased by 499 g C m(-2) in the
      spruce stand at Unterluss and by 274 g C m(-2) in the beech stand at Soiling
      following compost application whereas soil respiration of the other four stands
      was not affected. The increases in soil respiration of the two stands were
      explained by improved microbial decomposition of soil organic matter. The DOC
      concentrations and fluxes in throughfall and seepage water at 10- and 100-cm
      depths were determined from August 1997 to March 2000. In the control plots,
      cumulative DOC outputs at 10 cm ranged between 57 and 95 g C m(-2), with the
      highest rates in the pine stands. Compost treatment significantly increased
      cumulative DOC outputs by 31 to 69 g C m(-2) at 10 cm and by 0.3 to 6.6 g C m(-2)
      at 100 cm. The mineral soils between the 10- and 100-cm depths acted as
      significant sinks for DOC, as shown by much lower cumulative outputs at 100 cm of
      3 to 11 g C m(-2) in the control and 6 to 16 g C m(-2) in the compost plots. Our
      results suggest that a single, moderate application of mature compost to nutrient
      depleted forest soils has little effect on C losses to the atmosphere and ground
      water.

PMID- 14964363
TI  - Soil variables for predicting potential phosphorus release in Swedish
      noncalcareous soils.
AB  - The accumulation of P in agricultural soils due to fertilization has increased
      the risk of P losses from agricultural fields to surface waters. In risk
      assessment systems for P losses, both P release from soil to solution and
      transport mechanisms need to be considered. In this study, the overall objective
      was to identify soil variables for prediction of potential P release from soil to
      solution. Soils from nine sites of the Swedish long-term fertility experiment
      were used, each with four soil P levels. Phosphorus extractable with CaCl2 was
      used as an estimate of potential P release from soil to solution. Ammonium
      lactate-extractable phosphorus (P-AL) or NaHCO3-extractable phosphorus (Olsen P)
      could not be used alone for prediction of potential P release since soils with
      high phosphorus sorption capacity (PSC) released less P than soils with low PSC
      at the same soil test phosphorus (STP) level. Degree of phosphorus saturation
      (DPS) was calculated as Olsen P or P-AL as a percentage of PSC derived from P
      sorption isotherms or from Fe and Al extractable in ammonium oxalate. The CaCl2
      extractable total phosphorus (CaCl2-TP) was exponentially related to these DPS
      values (r2 > or = 0.79). The CaCl2-TP was also linearly related to ratios between
      Olsen P or P-AL and a single-point phosphorus sorption index (PSI; r2 > or =
      0.86). These ratios, which are easily determined and gave good correlations with
      CaCl2-TP, seemed to be the most useful estimates of potential P release for risk
      assessment systems.

PMID- 14964364
TI  - An environmental threshold for degree of phosphorus saturation in sandy soils.
AB  - There is critical need for a practical indicator to assess the potential for
      phosphorus (P) movement from a given site to surface waters, either via surface
      runoff or subsurface drainage. The degree of phosphorus saturation (DPS), which
      relates a measure of P already adsorbed by a soil to its P adsorption capacity,
      could be a good indicator of that soil's P release capability. Our primary
      objective was to find a suitable analytical protocol for determining DPS and to
      examine the possibility of defining a threshold DPS value for Florida's sandy
      soils. Four farmer-owned dairy sprayfields were selected within the Suwannee
      River basin and soil profiles were randomly obtained from each site, as well as
      from adjacent unimpacted sites. The soil samples were divided either by horizon
      or depth, and DPS was determined for each soil sample using ammonium-oxalate
      (DPS(Ox)), Mehlich-1 (DPS(M1)), and Mehlich-3 (DPS(M3)) extracts. All methods of
      DPS calculations were linearly related to one another (r2 > 0.94). Relationships
      between water-soluble P and DPS indicate that the respective change points are:
      DPS(Ox) = 20%, DPS(M1) = 20%, and DPS(M3) = 16%. These relationships include
      samples from Ap, E, and Bt horizons, and various combinations thereof, suggesting
      that DPS values can be used as predictors of P loss from a soil irrespective of
      the depth of the soil within a profile. Taking into consideration the change
      points, confidence intervals, agronomic soil test values, and DPS values from
      other studies, we suggest replacing Mehlich-1 P values in the Florida P Index
      with the three DPS categories (DPS(M1) = <30, 30-60, and >60%) to assign
      different P loss ratings in the P Index.

PMID- 14964365
TI  - Simulating nitrate drainage losses from a Walnut Creek watershed field.
AB  - This study was designed to evaluate the improved version of the Root Zone Water
      Quality Model (RZWQM) using 6 yr (1992-1997) of field-measured data from a field
      within Walnut Creek watershed located in central Iowa. Measured data included
      subsurface drainage flows, NO3-N concentrations and loads in subsurface drainage
      water, and corn (Zea mays L.) and soybean [Glycine mar (L.) Merr.] yields. The
      dominant soil within this field was Webster (fine-loamy, mixed, superactive,
      mesic Typic Endoaquolls) and cropping system was corn-soybean rotation. The model
      was calibrated with 1992 data and was validated with 1993 to 1997 data.
      Simulations of subsurface drainage flow closely matched observed data showing
      model efficiency of 99% (EF = 0.99), and difference (D) of 1% between measured
      and predicted data. The model simulated NO3-N losses with subsurface drainage
      water reasonably well with EF = 0.8 and D = 13%. The simulated corn grain yields
      were in close agreement with measured data with D < 10%. Nitrogen-scenario
      simulations demonstrated that corn yield response function reached a plateau when
      N-application rate exceeded 90 kg ha(-1). Fraction of applied N lost with
      subsurface drainage water varied from 7 to 16% when N-application rate varied
      from 30 to 180 kg ha(-1) after accounting for the nitrate loss with no-fertilizer
      application. These results indicate that the RZWQM has the potential to simulate
      the impact of N application rates on corn yields and NO3-N losses with subsurface
      drainage flows for agricultural fields in central Iowa.

PMID- 14964366
TI  - Assessment of a delta15N isotopic method to indicate anthropogenic eutrophication
      in aquatic ecosystems.
AB  - Increased anthropogenic delivery of nutrients to water bodies, both freshwater
      and estuarine, has caused detrimental changes in habitat, food web structure, and
      nutrient cycling. Nitrogen-stable isotopes may be suitable indicators of such
      increased nutrient delivery. In this study, we looked at the differences in
      response of macrophyte delta15N values to anthropogenic N across different
      taxonomic groups and geographic regions to test a stable isotopic method for
      detecting anthropogenic impacts. Macrophyte delta15N values increased with
      wastewater input and water-column dissolved inorganic nitrogen (DIN)
      concentration. When macrophytes were divided into macroalgae and plants, they
      responded similarly to increases in wastewater N, although macroalgae was a more
      reliable indicator of both wastewater inputs and water-column DIN concentrations.
      Smooth cordgrass (Spartina alterniflora Loisel.) Delta15N increased uniformly
      with wastewater inputs across a geographic range. We used the relationship
      derived between S. alterniflora and relative wastewater load to predict
      wastewater loads in locations lacking quantitative land use data. The predictions
      matched well with known qualitative information, proving the use of a stable
      isotopic method for predicting wastewater input.

PMID- 14964367
TI  - Effect of alkaline-stabilized biosolids on alfalfa molybdenum and copper content.
AB  - Agricultural utilization of biosolids poses a potential risk to ruminant animals
      due to transfer of Mo from biosolids to forage to the animal in amounts large
      enough to suppress Cu uptake by the animal. Alkaline-stabilized biosolids (ASB)
      must be given particular consideration in assessment of Mo risk because the high
      pH of these biosolids could increase Mo and decrease Cu uptake by forage legumes.
      In this 3-yr field experiment, ASB and ground agricultural limestone (AL) were
      applied based on their alkalinity at rates equivalent to 0, 0.5, 1.0, and 2.0
      times the lime requirement of the soil and alfalfa (Medicago sativa L.) was
      grown. Alfalfa yield was similar with AL and ASB except in the second year when
      ASB produced larger yields, apparently due to increased B availability with ASB.
      Application of ASB did not detectably increase extractable soil Mo (0- to 15-cm
      depth), but increased alfalfa Mo uptake in all cuttings with yield-weighted
      uptake coefficients (UCs) of 8.07 and 7.11 following the first and second ASB
      applications, respectively. Although ASB increased extractable soil Cu, and
      alfalfa Cu content was greater with ASB than with AL, yield-weighted alfalfa Cu
      to Mo ratio was decreased by ASB to levels near 3. These results suggest that ASB
      may have a greater effect on Mo uptake and Cu to Mo ratio of forage legumes than
      do other biosolids. Additional research is needed to determine implications of
      larger Mo cumulative loading with ASB for Mo risk, particularly in the soil pH
      range of 7 to 8.

PMID- 14964368
TI  - Lead reduction and redistribution in the forest floor in New Hampshire northern
      hardwoods.
AB  - Because of the affinity of organic matter for lead, atmospheric loadings of this
      pollutant have been strongly retained in the forest floor. With the regulation of
      Pb emissions, loadings have decreased. We measured changes in Pb in forest floor
      horizons at a variety of northern hardwood sites in New Hampshire from the late
      1970s to the 1990s. In all seven of the sites in which horizons were
      distinguished within the forest floor, Pb was found to be declining in the upper
      (Oie) horizon, but not in the underlying Oa and A horizons. At the Hubbard Brook
      Experimental Forest (HBEF), this loss from the Oie resulted in a 36% loss of Pb
      from the forest floor as a whole between 1976 and 1997 (p < 0.001). In contrast,
      in six stands in the Bartlett Experimental Forest (BEF), losses of Pb averaging
      >50% from the Oi and Oe horizons (p = 0.01) between 1979 and 1994 were
      compensated by gains in the Oa and A horizons. Similarly, at seven additional
      stands in the White Mountain National Forest, changes in the forest floor as a
      whole from 1980 to 1995 were not statistically significant (redistribution within
      the forest floor was not evaluated at these sites). Lead concentrations were
      highest in the Oe or Oie in the 1970s, but were highest in the Oa horizon in the
      1990s. There was no significant pattern of Pb loss or retention as a function of
      stand age across all the sites.

PMID- 14964369
TI  - Combinatory chemical and biological approaches to investigate metal elements in
      agricultural runoff water.
AB  - As part of a project studying the interactions between farming practices, soil
      erosion processes, and fate of agricultural pollutants into runoff waters, we
      conducted a pilot study to investigate the relationship between metal contents
      and metallothionein-2A (MT-2A) as a bioindicator of metal exposure. Runoff water
      samples were collected between May and November 1999 at the point of outlet of an
      elementary watershed located in the Paris basin. Selected metals (Al, As, Cd, Cr,
      Cu, Pb, Hg, Ni, and Zn) were analyzed using conventional techniques. In parallel,
      human T cells were exposed to water samples for 6 and 18 h and then cell
      viability and MT-2A gene expression were measured. Results show that among the 10
      water samples tested, Al and Zn predominate (highest values = 4.9 and 2.6 microM,
      respectively), while other metals were below the microM level. Five out of 10
      samples induced MT-2A gene expression (30-80% increase at 18 h) as compared with
      the control. When comparing MT-2A induction profile with metals contents, no
      obvious correlation was found, suggesting that additional components or
      parameters are involved. Finally, there was an apparent inverse relationship
      between Ca concentration and MT-2A gene induction. Although still preliminary, in
      the absence of longer monitoring, this study shows that MT-2A gene expression is
      a useful tool to complement chemical analysis in assessing metal elements in
      water. These combinatory approaches will be pursued and integrated in an ongoing
      watershed field research project.

PMID- 14964370
TI  - Sorption and biodegradability of sludge bacterial extracellular polymers in soil
      and their influence on soil copper behavior.
AB  - Bacterial extracellular polymers (BEP) affect the translocation and fate of
      organic and inorganic pollutants in terrestrial and aquatic ecosystems. In this
      study, BEP from activated sludge was compared with sludge dissolved organic
      matter (DOM) in terms of behavior and effects on the mobilization and
      bioavailability of Cu in a well-aged Cu-contaminated orchard sandy loam. Addition
      of sludge BEP (10-200 mg dissolved organic carbon [DOC] L(-1)) to the soil
      resulted in 1.6- to 12.8-fold-higher soil soluble Cu concentration over the
      control and 1.3- to 2.2-fold over sludge DOM of the same concentration.
      Consequently, the Cu uptake by the ryegrass (Lolium perenne L., cv. Target) grown
      in the soil was increased by 31% due to interval watering of 100 mg DOC L(-1) of
      sludge BEP solution in a 35-d period. The influence of sludge BEP on mobilizing
      soil Cu could be maintained as long as 60 d or more, depending on BEP
      biodegradation status. The findings that sludge BEP promoted Cu mobilization and
      bioavailability could be attributed to less adsorption of BEP by soil, slow
      degradation, and higher affinity with Cu. For example, after 3 wk of aerobic
      incubation, the soluble Cu present in the sludge DOM-treated soil was reduced to
      about the level of the control, while the concentration of soluble Cu in BEP
      treated soil was 6.2 times higher than that in the control. Therefore, sludge BEP
      could act as a facilitated-transport carrier of Cu. The environmental risk of Cu
      should receive much attention if BEP is incorporated into soils.

PMID- 14964371
TI  - Heavy metals in an urban watershed in southeastern Michigan.
AB  - The occurrence of heavy metals in the soil was measured over a period of several
      years to determine background concentrations in a heavily urbanized watershed in
      southeastern Michigan. A spatially dispersed sample was collected to capture the
      inherent variability of the soils and historic land use. The analysis focused on
      14 metals (antimony, arsenic, barium, beryllium, cadmium, chromium, copper, lead,
      mercury, nickel, selenium, silver, thallium, and zinc) that are part of the
      USEPA's list of the 129 most common pollutants. Metal concentrations were
      measured at three depths: near-surface (<0.5 m), shallow subsurface (0.5-10 m),
      and depths greater than 10 m across six soil units in glacial terrain. Additional
      analyses assessed the metal concentrations in each depth profile across three
      general land use categories: residential, commercial, and industrial. Metal
      concentrations were the highest in the near-surface with Pb present at
      concentrations averaging 15.5 times that of background in industrial areas and
      approximately 16 times background in residential areas. Cadmium, Hg, and Zn were
      also present in surface soils at levels of several times that of background. The
      highest concentrations of each of these metals were present in the clay-rich
      soils located in the eastern, more urbanized and industrialized part of the
      watershed. Metals detected at elevated concentrations decreased in concentration
      with increasing depth and distance from the urbanized and industrialized center
      of the watershed. Statistically significant differences in the concentrations of
      heavy metals were also noted between the land use categories, with Cd, Cr, Cu,
      Pb, Ni, and Zn observed within industrial areas at mean concentrations several
      times greater than background levels.

PMID- 14964372
TI  - Arsenic availability from chromated copper arsenate (CCA)-treated wood.
AB  - Lumber used to construct raised garden beds is often treated with chromated
      copper arsenate (CCA). This project aimed to determine (i) how far As, Cu, and Cr
      had diffused away from CCA-treated wood surfaces in raised garden beds under
      realistic conditions, (ii) the uptake of these elements by crops, and (iii) the
      effect of CCA solution on soil bacteria. This study showed that As, Cu, and Cr
      diffuse into soil from CCA-treated wood used to construct raised garden beds. To
      determine crop uptake of these elements, contaminated soil 0 to 2 cm from the
      treated wood was obtained from two different beds (40-50 mg kg(-1) As); control
      soil was collected 1.5 m away from the treated wood (<3-10 mg kg(-1) As). Four
      replicates of carrot (Daucus carota var. sativus Hoffm. cv. Thumbelina), spinach
      (Spinacia oleracea L. cv. Indian Summer), bush bean (Phaseolus vulgaris L. cv.
      Provider), and buckwheat (Fagopyrum esculentum Moench cv. Common) were grown in
      pots containing these soils in a greenhouse. After harvest, plant materials were
      dried, ground, digested, and analyzed for As by inductively coupled plasma
      hydride generation (ICP-HG). Concentrations of As in all crops grown in
      contaminated soils were higher than those from control soils. The levels of As in
      the crops remained well below the recommended limit for As set by the United
      States Public Health Service (2.6 mg kg(-1) fresh wt.). To determine if bacteria
      in soils 0 to 2 cm from the treated wood had higher resistance to Type C
      chromated copper arsenate (CCA-C) solution than those from reference soils,
      dilution plates were set up using quarter-strength tryptic soy agar (TSA) media
      and 0 to 22.94 g L(-1) (0-1.25% v/v) CCA-C working solution. The microorganisms
      from soils adjacent to treated wood had greater growth on the CCA-amended media
      than those from reference soils outside the bed.

PMID- 14964373
TI  - Modeling organic carbon dynamics and cadmium fate in long-term sludge-amended
      soil.
AB  - A model is described that may help to resolve uncertainty and controversy over
      the long-term consequences of sludge applications to arable land, especially with
      regard to the effects of sludge adsorption characteristics on trace metal
      solubility and bioavailability (e.g., the sludge "time bomb" or sludge
      "protection" hypotheses). Mass balances of organic and inorganic material derived
      from sludge and crop residues are simulated. Each pool has a potentially
      different adsorption affinity for trace metals, and this leads to changes in the
      adsorption capacity of sludge-amended soil that influence leaching and crop
      uptake. Model simulations were compared with measured changes in organic carbon
      and ethylenediaminetetraacetic acid (EDTA)-extractable cadmium contents in a clay
      loam soil following 41 years of sludge applications. The model adequately
      reproduced the data, although discrepancies in the vertical distribution of Cd
      were attributed to the effects of macropore transport and root-uptake driven
      recirculation. A Monte Carlo sensitivity analysis demonstrated that the most
      important parameters affecting leaching and crop uptake were the Cd loading and
      parameters controlling adsorption, especially the partition coefficient for
      sludge-derived inorganic material and the exponent regulating the effect of pH on
      sorption. Scenario simulations show that no general conclusions can be drawn with
      respect to the validity of the sludge "time bomb" and sludge "protection"
      hypotheses. Either may occur, or neither, depending on three key system
      parameters: the ratio of sludge adsorption capacity to the initial adsorption
      capacity of the soil, the proportion of the sludge adsorption capacity
      contributed by the inorganic fraction, and the sludge Cd loading.

PMID- 14964374
TI  - Dynamics of potassium leaching on a hillslope grassland soil.
AB  - There have been only a few studies of potassium (K) losses from grassland
      systems, and little is known about their dynamics, especially in relation to
      nitrogen (N) management. A study was performed during the autumn and winter of
      1999 and 2000 to understand the effects of N and drainage on the dynamics of K
      leaching on a hillslope grassland soil in southwestern England. Two N application
      rates were studied (0 and 280 kg N ha(-1) yr(-1)), both with and without tile
      drainage. Treatments receiving N also received farmyard manure (FM). Higher total
      K losses and K concentrations in the leachates were found in the N + FM
      treatments (150 and 185% higher than in 0 N treatments), which were related to K
      additions in the FM. Drainage reduced K losses by 35% because of an increase in
      dry matter production and a reduction in overland and preferential flow. The
      pattern of change in K concentration in the leachates was associated with
      preferential flow at the beginning of the drainage season and with matrix flow
      later in winter, and was best described by a double exponential curve. Rainfall
      intensity and the autumn application of FM were the main determinants of K losses
      by leaching. The study provided new insights into the relationships between soil
      hydrology, rainfall, and K leaching and its implications for grassland systems.

PMID- 14964375
TI  - Dissolved organic nitrogen regulation in freshwaters.
AB  - Dissolved organic nitrogen (DON) has been hypothesized to play a major role in N
      cycling in a variety of ecosystems. Our aim was to assess the seasonal and
      concentration relationships between dissolved organic carbon (DOC), DON, and NO3-
      within 102 streams and 16 lakes within catchments of differing complexity
      situated in Wales. Further, we aimed to assess whether patterns of land use, soil
      type, and vegetation gave consistent trends in DON and dissolved inorganic
      nitrogen (DIN) relationships over a diverse range of catchments. Our results
      reinforce that DON constitutes a significant component of the total dissolved N
      pool typically representing 40 to 50% of the total N in streams and lakes but
      sometimes representing greater than 85% of the total dissolved N. Generally, the
      levels of DON were inversely correlated with the concentration of DIN. In
      contrast to DIN concentrations, which showed distinct seasonality, DON showed no
      consistent seasonal trend. We hypothesize that this reflects differences in the
      bioavailability of these two N types. The amount of DON, DOC, and DIN was
      significantly related to soil type with higher DON export from Histosol-dominated
      catchments in comparison with Spodosol-dominated watersheds. Vegetation cover
      also had a significant effect on DON concentrations independent of soil type with
      a nearly twofold decrease in DON export from forested catchments in comparison
      with nonforested watersheds. Due to the diversity in catchment DON behavior, we
      speculate that this will limit the adoption of DON as a broad-scale indicator of
      catchment condition for use in monitoring and assessment programs.

PMID- 14964376
TI  - Mathematical modeling of phosphorus losses from land application of hog and
      cattle manure.
AB  - Mathematical models may provide a means to estimate phosphorus (P) losses from
      land application of manure. Phosphorus losses typically occur during brief
      episodes of runoff and erosion. Models must be able to simulate P losses during
      these episodes by representing the basic chemical, physical, and biological
      processes by which these losses occur. The mathematical model ecosys combines
      dynamic distributed flow of solutes and nonsolutes through runoff and erosion
      with convective-dispersive transport of solutes, and both biologically and
      thermodynamically driven transformations between solutes and nonsolutes. This
      model was tested against P lost in runoff, erosion, and leachate measured during
      90 min of controlled rainfall at 65 mm h(-1) on soils from six sites at which
      different rates of manure had been applied over the previous 3 to 6 yr. Transport
      and transformation kinetics in the model enabled it to simulate changes of
      dissolved inorganic phosphorus (DIP) in runoff from >1.0 to <0.05 mg L(-1) and
      changes of total phosphorus (TP) in sediment from 15 to 3 mg L(-1) measured
      during controlled rainfall on soils with diverse P contents. Results from 60-yr
      model runs using these kinetics with different application rates of cattle manure
      indicated that (i) a positive interaction exists between annual rainfall and
      application rate on P losses and (ii) rates greater than 30 Mg ha(-1) yr(-1)
      would cause TP concentrations in water leaving the site to rise above acceptable
      limits. The interaction between rainfall and rate suggests that P losses from
      manure application at any site should be assessed under the upper range of likely
      rainfall intensities.

PMID- 14964377
TI  - Degradation and mobility of linear alkylbenzene sulfonate and nonylphenol in
      sludge-amended soil.
AB  - Degradation and mobility of the surfactants linear alkylbenzene sulfonate (LAS)
      and nonylphenol (NP) were investigated in a lysimeter study using a sandy loam
      soil and 45-cm soil columns. Anaerobically digested sewage sludge was
      incorporated in the top-15-cm soil layer to an initial content of 38 mg LAS and
      0.56 mg NP kg(-1) dry wt., respectively. Spring barley (Hordeum vulgare L.) was
      sown onto the columns. The lysimeters were placed outdoors and therefore received
      natural precipitation, but were also irrigated to a total amount of water
      equivalent to 700 mm of precipitation. Leachate and soil samples from three soil
      layers were collected continuously during a growth period of 110 d. Leachate
      samples and soil extracts were concentrated by solid-phase extraction (SPE) and
      analyzed using high performance liquid chromatography (HPLC) with fluorescence
      detection. The concentrations in the top-15-cm soil layer declined to 25 and 45%
      of the initial contents for LAS and NP, respectively, within the first 10 d of
      the study. At the end of the study, less than 1% LAS was left, while the NP
      content was below the detection limit. Assuming first-order degradation kinetics,
      half-lives of 20 and 37 d were estimated for LAS and NP, respectively. The
      surfactants were not measured in leachate samples in concentrations above the
      analytical detection limits of 4.0 and 0.5 microg L(-1) for LAS and NP,
      respectively. In addition, neither LAS nor NP were measured in concentrations
      above the detection limits of 150 and 50 microg kg(-1) dry wt., respectively, in
      soil layers below the 15 cm of sludge incorporation, indicating negligible
      downward transport of the surfactants in the lysimeters.

PMID- 14964378
TI  - Infiltration of acetochlor and two of its metabolites in two contrasting soils.
AB  - To obtain data concerning the risk of leaching of acetochlor (2-chloro-2'-methyl
      6'-ethyl-N-ethoxymethyl-acetanilide) and its major metabolites, ethanesulfonic
      acid (ESA) and oxanilic acid (OA), to ground water, we studied the fate of these
      products in two different soil types (luvisol and calcisol) under the same
      weather conditions. The metabolites were detected in the soils as early as 7 d
      after application, indicating a rapid onset of acetochlor degradation.
      Ethanesulfonic acid was predominant over OA in the calcisol, regardless of time
      or depth, whereas the ESA to OA ratio varied with both time and depth in the
      luvisol. The maximum depths at which they were detected were 60 to 70 and 10 to
      20 cm for ESA and OA, respectively, in the luvisol, and 60 to 70 cm (maximum
      depth sampled) and 30 to 40 cm for ESA and OA, respectively, in the calcisol.
      Acetochlor was still detected in the surface layer of the two soils 344 d after
      its application, although the molecule was partially leached. The maximum depths
      at which acetochlor was detected (60-70 cm in the luvisol and 50-60 cm [maximum
      depth sampled] in the calcisol) were recorded during the first sampling 7 d after
      application. Acetochlor was not detected on later dates below the 30- to 40-cm
      layer in the calcisol or the 5- to 10-cm layer in the luvisol. The greater
      preferential flow in the luvisol, which would have favored leaching, might
      partially explain why the mass balances done 7 d after application were lower in
      the luvisol (approximately 26%) than in the calcisol (approximately 45%).

PMID- 14964379
TI  - Enzyme-linked immunosorbent assay for ultratrace determination of antibiotics in
      aqueous samples.
AB  - Two commercially available enzyme-linked immunosorbent assay (ELISA) kits that
      are commonly used for tylosin or tetracycline residues in meat and milk were
      adapted for ultratrace analysis of these antibiotics in surface and ground
      waters. These two antibiotics are commonly fed to swine, turkeys, and cattle at
      subtherapeutic doses for growth promotion purposes. Both ELISA techniques were
      found to be highly sensitive and selective for the respective antibiotics with
      detection limits of 0.10 and 0.05 microg L(-1) for tylosin and tetracycline,
      respectively. The recovery of both tylosin and tetracycline from spiked samples
      of lake waters, runoff samples, soil saturation extracts, and nanopure water was
      close to 100%. Tetracycline ELISA was highly specific for tetracycline and
      chlortetracycline but not for other forms of tetracycline (oxytetracycline,
      demeclocycline, and doxycycline). Analysis of a few liquid swine manure samples
      by liquid chromatography-mass spectrometry (LC-MS) showed lower concentrations
      for chlortetracycline as compared with concentrations obtained using ELISA.
      However, the concentrations of tylosin from ELISA were comparable with that of LC
      MS. The lower concentrations of chlortetracycline obtained by LC-MS in manure
      samples indicate the presence of other similar or transformed compounds that were
      detected by ELISA but not determined by LC-MS. These results indicate that both
      ELISA kits can be useful tools for low-cost screening of tylosin, tetracycline,
      and chlortetracycline in environmental waters. Furthermore, both ELISA procedures
      are rapid, portable, and easily adaptable for testing of multiple samples
      simultaneously.

PMID- 14964380
TI  - Adsorption and clay-catalyzed degradation of erythromycin A on homoionic clays.
AB  - Erythromycin has been widely used in food-producing animals and in humans, and is
      frequently detected as an organic pollutant in U.S. streams. In batch experiments
      with homoionic clays, the Freundlich isotherms were determined at 10 and 25
      degrees C. The adsorption of erythromycin A was strongly influenced by clay type,
      exchanged cations, the pH of the bulk solutions, and the acidity of clay
      surfaces. The formation of clay-erythromycin A complexes was thermodynamically
      favorable except for K+- and Fe3+-exchanged montmorillonites, since the reactions
      were exothermic (deltaH(o) > 0) and the systems became stable (deltaS(o) > 0).
      Clays catalyzed the erythromycin A degradation by the hydrolysis of the neutral
      sugar and the multiple dehydrations. The surface acidity of clay surface enhanced
      the rate of clay-catalyzed degradation of erythromycin A. In addition, the Fe3+
      exchanged clay minerals seemed to have an electrostatic interaction with the
      erythromycin A molecule, by which the hydrolysis of the neutral sugar was
      influenced.

PMID- 14964381
TI  - Formation of pi-pi complexes between phenanthrene and model pi-acceptor humic
      subunits.
AB  - Pi-pi interactions may play a role in association of aromatic compounds with
      natural organic substances. Complexation in aqueous solvents was studied between
      the pi donor, phenanthrene (PHEN), and model pi-acceptor species (quinones and N
      heteroaromatic cations) that represent certain functional units of humic
      substances. Charge-transfer bands in the UV and ring-current shifts in the proton
      nuclear magnetic resonance (NMR) spectrum confirmed the face-to-face, pi-pi donor
      acceptor nature of the bond. Complexation constants were obtained by the
      solubility enhancement method; solubility enhancements up to 2500 were found.
      Ruled out as predominant causes of solubility enhancement were monomer
      desolvation (i.e., "hydrophobic" effects), partitioning into micelles, pi-cation
      interactions, and pi-hydrogen bonding. Acceptor self-stacking and formation of
      higher-stoichiometry acceptor-donor complexes had to be considered in evaluating
      donor-acceptor equilibria in some cases. The affinity of acceptor for PHEN
      followed the order of increasing pi-acceptor strength and varied strongly with
      the degree of ring overlap with PHEN. Complexation between PHEN and the free
      solution faces of an acceptor was less favorable than intercalation of PHEN
      between two acceptor units in a stack. A positive hydrophobic effect on
      complexation was evident in water mixtures with acetone or methanol and found to
      correlate with the number of faces of PHEN requiring desolvation to form the
      complex. When hydrophobic effects are subtracted out, the pi-pi complex actually
      becomes favored as the solvent water content and polarity decline. The results
      suggest that phenanthrene, and by implication other donor aromatic compounds, are
      capable of forming pi-pi interactions with appropriate humic fragments.

PMID- 14964382
TI  - Characterization of cation-pi interactions in aqueous solution using deuterium
      nuclear magnetic resonance spectroscopy.
AB  - Chemical interactions of aromatic organic contaminants control their fate,
      transport, and toxicity in the environment. Recent molecular modeling studies
      have suggested that strong interactions can occur between the pi electrons of
      aromatic molecules and metal cations in aqueous solutions and/or on mineral
      surfaces, and that such interactions may be important in some environmental
      systems. However, spectroscopic evidence for these so-called cation-pi
      interactions has been extremely limited to date. In this paper, cation-pi
      interactions in aqueous salt solutions were characterized via 2H nuclear magnetic
      resonance (NMR) spin-lattice relaxation times (T1) and calculations of molecular
      correlation times (tau(c)) for a series of perdeuterated (d6-benzene) benzene
      cation complexes. The T1 values for d6-benzene decreased with increasing
      concentrations of LiCl, NaCl, KCl, RbCl, CsCl, and AgNO3, with the largest
      effects observed in the AgNO3 and CsCl solutions. Upon normalizing tau(c) values
      by solution viscosity effects, an overall affinity trend of Ag+ >> Cs+ > K+ > Rb+
      > Na+ > Li+ was derived for the d6-benzene-cation complexes. The ability of Ag+
      to complex d6-benzene was significantly reduced upon addition of NH3, which
      strongly coordinates Ag+ at high pH. Results with d6-benzene, d8-naphthalene, d2
      dichloromethane, and d12-cyclohexane in 0.1 M methanolic salt solutions confirmed
      that spin-lattice relaxation rates are characterizing cation-pi interactions. The
      relatively strong cation-pi bonding observed between Ag+ and aromatic
      hydrocarbons probably results from covalent interactions between the aromatic pi
      electrons and the d orbitals of Ag+, in addition to the normal electrostatic
      interaction.

PMID- 14964383
TI  - Nutrient retention efficiency in streams receiving inputs from wastewater
      treatment plants.
AB  - We tested the effect of nutrient inputs from wastewater treatment plants (WWTPs)
      on stream nutrient retention efficiency by examining the longitudinal patterns of
      ammonium, nitrate, and phosphate concentrations downstream of WWTP effluents in
      15 streams throughout Catalonia (Spain). We hypothesized that large nutrient
      loadings would saturate stream communities, lowering nutrient retention
      efficiency (i.e., nutrient retention relative to nutrient flux) relative to less
      polluted streams. Longitudinal variation in ambient nutrient concentration
      reflected the net result of physical, chemical, or biological uptake and release
      processes. Therefore, gradual increases in nutrient concentration indicate that
      the stream acts as a net source of nutrients to downstream environments, whereas
      gradual declines indicate that the stream acts as a net sink. In those streams
      where gradual declines in nutrient concentration were observed, we calculated the
      nutrient uptake length as an indicator of the stream nutrient retention
      efficiency. No significant decline was found in dilution-corrected concentrations
      of dissolved inorganic nitrogen (DIN) and phosphate in 40 and 45% of streams,
      respectively. In the remaining streams, uptake length (estimated based on the
      decline of nutrient concentrations at ambient levels) ranged from 0.14 to 29 km
      (DIN), and from 0.14 to 14 km (phosphate). Overall, these values are longer
      (lower retention efficiency) than those from nonpolluted streams of similar size,
      supporting our hypothesis, and suggest that high nutrient loads affect fluvial
      ecosystem function. This study demonstrates that the efficiency of stream
      ecosystems to remove nutrients has limitations because it can be significantly
      altered by the quantity and quality of the receiving water.

PMID- 14964384
TI  - Alachlor and bentazone losses from subsurface drainage of two soils.
AB  - Atrazine (6-chloro-N2-ethyl-N4-isopropyl-1,3,5-triazine-2,4-diamine) is
      frequently detected at high concentrations in ground water. Bentazone [3
      isopropyl-1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide] plus alachlor (2-chloro
      2',6'-diethyl-N-methoxymethylacetanilide) is a potential herbicide combination
      used as a substitute for atrazine. Thus, the objective of this study was to
      assess the environmental risk of this blend. Drainage water contamination by
      bentazone and alachlor was assessed in silty clay (Vertic Eutrochrept) and silt
      loam (Aquic Hapludalf) soils under the same management and climatic conditions.
      Drainage volumes and concentrations of alachlor and bentazone were monitored
      after application. Herbicides first arrived at the drains after less than 1 cm of
      net drainage. This is consistent with preferential flow and suggests that about
      3% of the pore volume was active in rapid transport. During the monitoring
      periods, bentazone losses were higher (0.11-2.40% of the applied amount) than
      alachlor losses (0.00-0.28%) in the drains of the silty clay and silt loam. The
      rank order of herbicide mass losses corresponded with the rank order of herbicide
      adsorption coefficients. More herbicide residues were detected in drainage from
      the silty clay, probably due to preferential flow and more intensive drainage in
      this soil than the silt loam. Surprisingly, herbicide losses were higher in the
      drains of both soils in the drier of the two study years. This could be explained
      by the time intervals between the treatments and first drainage events, which
      were longer in the wetter year. Results suggest that the drainage phases occurred
      by preferential flow in the spring-summer period, with correspondingly fast
      leaching of herbicides, and by matrix flow during the fall-winter period, with
      slower herbicide migration.

PMID- 14964385
TI  - Seasonal variation of herbicide concentrations in prairie farm dugouts.
AB  - Prairie farm dugouts are frequently constructed for use as potable water sources.
      Consequently, cumulative pesticide inputs via atmospheric deposition and surface
      runoff may constitute a risk to human health. Since, relative to other
      pesticides, herbicides are used in greatest amount on the Canadian prairies,
      herbicide concentrations were intensively monitored in three dugouts over three
      growing seasons. Herbicides were detected in the water of all three dugouts each
      growing season which may reflect cumulative inputs from atmospheric and surface
      processes over the lifetimes of the dugouts, which varied from 11 to 22 yr.
      Detections, which were not continuous, tended to be seasonal in nature. During
      the 3-yr study, detections were most frequent during the spring application
      period and late fall following dugout turnover. Between these periods, herbicide
      concentrations generally decreased to below detection limits. The reappearance of
      herbicides in the dugout water during fall turnover and in concentrations
      generally greater than those present during the spring application period suggest
      that, under appropriate environmental conditions, the bottom sediments may act as
      a source of herbicides to the water column. In general, herbicide inputs due to
      deposition of application drift did not result in detectable concentrations of
      herbicides in the dugouts. In the only year that winter samples were monitored,
      herbicides were also detected during ice cover. On the basis of monthly sampling
      over each growing season, median concentrations of 9 of the 10 herbicides
      monitored were less than 0.05 microg L(-1). The exception, 2,4-D, which has been
      used extensively on the Canadian prairies for more than 50 yr and in greatest
      amounts, was the most frequently detected herbicide. In no case did herbicide
      concentrations exceed Canadian drinking water guidelines; however, on occasion
      maximum herbicide concentrations did exceed aquatic life and irrigation water
      guidelines.

PMID- 14964386
TI  - Evaluating microbial purification during soil treatment of wastewater with
      multicomponent tracer and surrogate tests.
AB  - Soil treatment of wastewater has the potential to achieve high purification
      efficiency, yet the understanding and predictability of purification with respect
      to removal of viruses and other pathogens is limited. Research has been completed
      to quantify the removal of virus and bacteria through the use of microbial
      surrogates and conservative tracers during controlled experiments with three
      dimensional pilot-scale soil treatment systems in the laboratory and during the
      testing of full-scale systems under field conditions. The surrogates and tracers
      employed included two viruses (MS-2 and PRD-1 bacteriophages), one bacterium (ice
      nucleating active Pseudomonas), and one conservative tracer (bromide ion).
      Efforts have also been made to determine the relationship between viruses and
      fecal coliform bacteria in soil samples below the wastewater infiltrative
      surface, and the correlation between Escherichia coli concentrations measured in
      percolating soil solution as compared with those estimated from analyses of soil
      solids. The results suggest episodic breakthrough of virus and bacteria during
      soil treatment of wastewater and a 2 to 3 log (99-99.9%) removal of virus and
      near complete removal of fecal coliform bacteria during unsaturated flow through
      60 to 90 cm of sandy medium. Results also suggest that the fate of fecal coliform
      bacteria may be indicative of that of viruses in soil media near the infiltrative
      surface receiving wastewater effluent. Concentrations of fecal coliform in
      percolating soil solution may be conservatively estimated from analysis of
      extracted soil solids.

PMID- 14964387
TI  - Thermal analysis of whole soils and sediment.
AB  - Thermal analysis techniques were utilized to investigate the thermal properties
      of two soils and a lignite coal obtained from the International Humic Substances
      Society (IHSS), and sediment obtained from The Netherlands. Differential scanning
      calorimetry (DSC) revealed glass transition behavior of each sample at
      temperatures ranging from 52 degrees C for Pahokee peat (euic, hyperthermic
      Lithic Medisaprists), 55 degrees C for a Netherlands (B8) sediment, 64 degrees C
      for Elliott loam (fine, illitic, mesic Aquic Arguidolls), to 70 degrees C for
      Gascoyne leonardite. Temperature-modulated differential scanning calorimetry
      (TMDSC) revealed glass transition behavior at similar temperatures, and
      quantified constant-pressure specific heat capacity (Cp) at 0 degrees C from 0.6
      J g(-1) degrees C(-1) for Elliott loam and 0.8 J g(-1) degrees C(-1) for the
      leonardite, to 1.0 J g(-1) degrees C(-1) for the peat and the sediment. Glass
      transition behavior showed no distinct correlation to elemental composition,
      although Gascoyne Leonardite and Pahokee peat each demonstrated glass transition
      behavior similar to that reported for humic acids derived from these materials.
      Thermomechanical analysis (TMA) revealed a large thermal expansion followed by a
      matrix collapse for each sample between 20 and 30 degrees C, suggesting the
      occurrence of transition behavior of unknown origin. Thermal transitions
      occurring at higher temperatures more representative of glass transition behavior
      were revealed for the sediment and the peat.

PMID- 14964388
TI  - Bromide and nitrate movement through undisturbed soil columns.
AB  - Field experiments often assume that Br-, 14NO3(-)-N, and 15NO3(-)-N have similar
      leaching kinetics. This study tested this assumption. Twenty-four undisturbed
      soil columns (15-cm diameter) were collected from summit-shoulder, backslope, and
      footslope positions of a no-tillage field with a corn (Zea mays L.)-soybean
      [Glycine max (L.) Merr.] rotation. Each of the landscape positions had a
      different soil series. After conditioning the columns with 4 L of 0.01 M CaCl2 (2
      pore volumes), 15N-labeled Ca(NO3)2 and KBr were applied to the soil surface and
      leached with 4 L of 0.01 M CaCl2. Leachate was collected, weighed, and analyzed
      for NO3(-)-N, NH4(+)-N, 15N, 14N, and Br-. The total amount of 15NO3(-)-N and
      14NO3(-)-N collected in 1000, 2000, and 3000 mL of leachate was similar. These
      data suggest that 15N discrimination during leaching did not occur. Bromide
      leached faster through the columns than NO3(-)-N. The more rapid transport of Br-
      than NO3(-)-N was attributed to lower Br- (0.002 +/- 0.036 mg kg(-1)) than NO3(-)
      N (0.17 +/- 0.03 mg kg(-1)) sorption. Results from this study suggest that (i) if
      Br- is used to estimate NO3(-)-N leaching loss, then NO3(-)-N leaching losses may
      be overestimated by 25%; (ii) the potential exists for landscape position to
      influence anion retention and movement in soil; and (iii) 15N discrimination was
      not detected during the leaching process.

PMID- 14964389
TI  - Fly ash as a liming material for cotton.
AB  - A field experiment was conducted to determine the effect of fly ash from a coal
      combustion electric power facility on soil acidity in a cotton (Gossypium
      hirsutum L.) field. Fresh fly ash was applied to a Bosket fine sandy loam (fine
      loamy, mixed, thermic Mollic Hapludalf) soil with an initial soil pH(salt) of
      4.8. The fly ash was equivalent to 42 g kg(-1) calcium carbonate with 97% passing
      through a 60 mesh (U.S. standard) sieve. Fly ash was applied one day before
      cotton planting in 1999 at 0, 3.4, 6.7, and 10.1 Mg ha(-1). No fly ash was
      applied in 2000. Within 60 d of fly ash application in 1999, all rates of fly ash
      significantly increased soil pH above 6.0. Manganese levels in cotton petioles
      were reduced significantly by 6.7 and 10.1 Mg ha(-1) of fly ash. Soil boron (B)
      and sodium (Na) concentrations were significantly increased with fly ash. In
      1999, B in cotton leaves ranged from 72 to 84 mg kg(-1) in plots with fly ash
      applications. However, no visual symptoms of B toxicity in plants were observed.
      In 1999, cotton lint yield decreased on average 12 kg ha(-1) for each Mg of fly
      ash applied. In 2000, cotton yields were significantly greater for the residual
      3.4 and 6.7 Mg fly ash ha(-1) plots than the untreated check. Due to the adverse
      yield effects measured in the first year following application, fly ash would not
      be a suitable soil amendment for cotton on this soil at this time.

PMID- 14964390
TI  - Organic ligand effects on enzymatic dephosphorylation of myo-inositol hexakis
      dihydrogenphosphate in dairy wastewater.
AB  - Animal manure contains partially digested feed fiber and grains where phosphorus
      (P) is bound in organic compounds that include myo-inositol 1,2,3,5/4,6-hexakis
      dihydrogenphosphate or phytic acid (IP6). Information is needed on the effects of
      other (non-IP6) organic ligands (LIGND) on the enzymatic dephosphorylation of
      IP6, which is a potential source of dissolved orthophosphate P (PO4-P) in the
      soil-manure-water system. The effects of 1,2-cyclohexane diamino-tetraacetate
      (CDTA), diethylenetriamine-N,N,N',N'',N''-pentaacetate (DTPA), ethylenediamine
      N,N,N',N'-tetraacetate (EDTA), oxalate (OXA), and phthalate (PHTH) and LIGND to
      IP6 molar ratio and charge concentration ratio on IP6 dephosphorylation were
      studied to determine controlling mechanisms of IP6 persistence in manure.
      Solution PO4-P concentrations were analyzed by ion chromatography as the
      phosphomolybdate-ascorbic acid method partly includes IP6-P. Uncomplexed IP6
      dephosphorylation by Aspergillus ficuum (Reichardt) Henn. phytase EC 3.1.3.8 at
      pH 4.5 and 6 is unaffected by the presence of LIGNDs. As the concentrations of
      Ca2+, Al3+, or Fe3+ increase, dephosphorylation is reduced. Their inhibitory
      effect lessens in the presence of LIGNDs, in the following order: CDTA = EDTA >
      DTPA >> OXA > or = PHTH. Whether CDTA or EDTA is the most effective LIGND depends
      upon the acidity of the suspension and LIGND charge concentration, reducing the
      inhibitory effect of polyvalent counterions to the point of promoting the
      hydrolysis of a manure phytase-hydrolyzable phosphorus (PHP) fraction that is
      otherwise unavailable. Therefore, ligand-induced changes increase the
      mobilization and dephosphorylation of complexed organic P, above and beyond the
      simple dissolution of inorganic phosphates. An analytical method for potentially
      bioavailable PHP in animal manure should include a LIGND as extracting reagent.
      Also, potential LIGNDs in an organic carbon-rich dairy wastewater may increase
      the release of PHP and environmental dispersion of PO4-P.

PMID- 14964391
TI  - Runoff losses of phosphorus and nitrogen imported in sod or composted manure for
      turf establishment.
AB  - Nutrient loading on impaired watersheds can be reduced through export of sod
      grown with manure and export of composted manure for turf production on other
      watersheds. Effects of the sod and manure exports on receiving watersheds were
      evaluated through monitoring of total dissolved phosphorus (TDP) and N
      concentrations and losses in runoff from establishing turf. Three replications of
      seven treatments were established on an 8.5% slope of a Booneville soil (loamy
      skeletal, mixed, superactive Pachic Argicryolls). Three treatments comprised
      imported 'Tifway' bermudagrass [Cynodon dactylon (L.) Pers. x C. transvaalensis
      Burtt-Davy) sod grown with composted dairy manure (382 or 191 kg P ha(-1)) or
      fertilizer (50 kg P ha(-1)). Three treatments were sprigged with Tifway and top
      dressed with either composted manure (92 or 184 kg P ha(-1)) or fertilizer (100
      kg P ha(-1)). The control was established bermudagrass [Cynodon dactylon (L.)
      Pers. var. Guymon]. During eight fall rain events, mean TDP concentration in
      runoff (7.8 mg L(-1)) from sprigged Tifway top-dressed with manure (84 kg P ha(
      1)) was 1.6 times greater than sod imported with 129 kg manure P ha(-1). During
      the first fall event, mass losses of TDP (232 mg m(-2)) and total Kjeldahl
      nitrogen (TKN) (317 mg m(-2)) from sprigged treatments top-dressed with manure or
      fertilizer were nearly three times greater than manure-grown sod. Percentages of
      manure P lost as TDP in runoff from imported sod were 33% of percentages lost
      from sprigged treatments top-dressed with manure. Sod grown with manure P rates
      of 190 kg P ha(-1) can be imported without increasing runoff losses of TDP
      compared with conventional fertilization of establishing turfgrass.

PMID- 14964392
TI  - Enzymatic hydrolysis of organic phosphorus in swine manure and soil.
AB  - Organic phosphorus (Po) exists in many chemical forms that differ in their
      susceptibility to hydrolysis and, therefore, bioavailability to plants and
      microorganisms. Identification and quantification of these forms may
      significantly contribute to effective agricultural P management. Phosphatases
      catalyze reactions that release orthophosphate (Pi) from Po compounds. Alkaline
      phosphatase in tris-HCl buffer (pH 9.0), wheat (Triticum aestivum L.) phytase in
      potassium acetate buffer (pH 5.0), and nuclease P1 in potassium acetate buffer
      (pH 5.0) can be used to classify and quantify Po in animal manure. Background
      error associated with different pH and buffer systems is observed. In this study,
      we improved the enzymatic hydrolysis approach and tested its applicability for
      investigating Po in soils, recognizing that soil and manure differ in numerous
      physicochemical properties. We applied (i) acid phosphatase from potato (Solanum
      tuberosum L.), (ii) acid phosphatases from both potato and wheat germ, and (iii)
      both enzymes plus nuclease P1 to identify and quantify simple labile monoester P,
      phytate (myo-inositol hexakis phosphate)-like P, and DNA-like P, respectively, in
      a single pH/buffer system (100 mM sodium acetate, pH 5.0). This hydrolysis
      procedure released Po in sequentially extracted H2O, NaHCO3, and NaOH fractions
      of swine (Sus scrofa) manure, and of three sandy loam soils. Further refinement
      of the approach may provide a universal tool for evaluating hydrolyzable Po from
      a wide range of sources.

PMID- 14964393
TI  - Solubility of phosphorus and heavy metals in potting media amended with yard
      waste-biosolids compost.
AB  - The potential risk of surface and ground water contamination by phosphorus (P)
      and heavy metals leached from compost-based containerized media has become an
      environmental concern. Solubility and fractionation of P and heavy metals were
      evaluated in media containing 0, 25, 50, 75, or 100% compost derived from
      biosolids and yard trimmings for potential impacts on the environment. As compost
      proportion in peat-based media increased from 0 to 100%, concentrations of total
      P, Cd, Cu, Ni, Pb, Zn, and Mn in the media increased whereas concentrations of
      total Co and Cr decreased. Except for Cu, all heavy metals in the water-soluble
      fraction decreased with increasing compost proportion in the media, because of
      higher Fe, Al, and Ca concentrations and pH values of the composts than the peat.
      When the media pH is controlled and maintained at normal range of plant growth
      (5.5-6.5), leaching of the heavy metals is minimal. Incorporation of compost to
      the peat-based media also decreased the proportion of total P that was water
      soluble. However, concentrations of bioavailable inorganic phosphorus (NaHCO3
      IP), readily mineralizable organic phosphorus (NaHCO3-OP), potentially
      bioavailable inorganic phosphorus (NaOH-IP), and potentially bioavailable organic
      phosphorus (NaOH-OP) were still higher in the media amended with compost because
      of higher total P concentration in the compost. Further study is needed to verify
      if less or no topdressing of chemical P fertilizer should be applied to the
      compost-amended media to minimize P effect on the environment when compost
      amended potting media are used for nursery or greenhouse crop production systems.

PMID- 14964394
TI  - Determination of phosphorus source coefficients for organic phosphorus sources:
      laboratory studies.
AB  - Phosphorus losses in runoff from application of manures and biosolids to
      agricultural land are implicated in the degradation of water quality in the
      Chesapeake and Delaware Inland Bays. We conducted an incubation study to
      determine the relative P solubility and bioavailability, referred to as P source
      coefficients (PSCs), for organic P sources, which are typically land-applied in
      the Mid-Atlantic USA. Nine organic and one inorganic (KH2PO4) P amendments were
      applied to an Evesboro loamy sand (mesic, coated Typic Quartzipsamments) at a
      rate of 60 mg P kg(-1) and incubated for 8 wk with subsamples analyzed at 2 and 8
      wk. There was an increase in Mehlich-3 P (M3-P), water-soluble P (WS-P), iron
      oxide strip extractable P (FeO-P), and Mehlich-3 P saturation ratio (M3-PSR) with
      P additions, which varied by P source. The trend of relative extractable WS-P,
      FeO-P, and M3-P generally followed the pattern: inorganic P > liquid and deep pit
      manures > manures and biosolids treated with metal salts or composted. We found
      significant differences in the availability of P from varying organic P sources.
      The use of PSCs may be beneficial when determining the risk of P losses from land
      application of manures and other organic P sources and could be used in risk
      assessments such as a P site index. These PSCs may also be useful for determining
      P application rates when organic P sources are applied to P deficient soils for
      use as a fertilizer source.

PMID- 14964395
TI  - Phosphorus fractionation in manure from swine fed traditional and low-phytate
      corn diets.
AB  - Traditional corn (Zea mays L.) (TC), the primary grain used in swine (Sus scrofa)
      diets, stores a majority of its P as phytate, which is largely unavailable for
      digestion by nonruminant animals. Low-phytate corn (LPC) contains similar amounts
      of total P but a smaller percentage of P as phytate. When fed to swine, LPC
      increases P utilization and reduces P content of manure. While differences in P
      content between manure from animals fed TC and LPC diets have been documented,
      solubility and lability of manure P have not been compared. Manure P was
      characterized in manure from swine fed either LPC or TC diets in 2000 and 2001.
      Total P was lower (20 vs. 34 g kg(-1)) and N to P ratio was higher (4.5 vs. 3.3)
      in LPC manure than in TC manure. Manures were sequentially extracted with
      deionized water, 0.5 M NaHCO3, 0.1 M NaOH, and 1.0 M HCl. Extracts were analyzed
      for inorganic and total P. Most P (approximately 80%) in the extracts was in the
      inorganic form. Concentration of P in the water-extractable fraction was lower
      for LPC manure (10.2 g kg(-1) in 2000 and 9.7 g kg(-1) in 2001) than for TC
      manure (13.6 g kg(-1) in 2000 and 17.0 g kg(-1) in 2001). Percentage of total P
      in each extract was in the order of: H2O (60%), HCl (22%), NaHCO3 (12%), NaOH
      (8%), and residue (<1%). Total P and distribution of P in extracts indicates
      swine are able to utilize more P contained in LPC feed but the composition of P
      excreted in LPC manure is similar to TC manure. Solubility, crop availability,
      and lability of P in LPC manure should be similar to that of TC manure.

PMID- 14964396
TI  - Dissolved phosphorus retention and release from a coastal plain in-stream
      wetland.
AB  - Dissolved phosphorus (DP) can be released from wetlands as a result of flooding
      or shifts in water column concentrations. Our objectives were to determine the
      long-term (1460 d) DP retention and release characteristics of an in-stream
      wetland, and to evaluate how these characteristics respond to flooding, draining,
      and changes in DP concentrations. The studied in-stream wetland drains an
      agriculturally intensive subwatershed in the North Carolina Coastal Plain region.
      The wetland's DP retention and release characteristics were evaluated by
      measuring inflow and outflow DP concentrations, DP mass balance, and DP movement
      across the sediment-water column interface. Phosphorus sorption isotherms were
      measured to determine the sediment's equilibria P concentration (EPCo), and
      passive samplers were used to measure sediment pore water DP concentrations.
      Initially, the in-stream wetland was undersized (0.31 ha) and released 1.5 kg of
      DP. Increasing the in-stream wetland area to 0.67 ha by flooding resulted in more
      DP retention (28 kg) and low outflow DP concentrations. Draining the in-stream
      wetland from 0.67 to 0.33 ha caused the release of stored DP (12.1 kg). Shifts
      both in sediment pore water DP concentrations and sediment EPCo values
      corroborate the release of stored DP. Reflooding the wetland from 0.33 to 0.85 ha
      caused additional release of stored DP into the outflowing stream (10.9 kg). We
      conclude that for a time period, this in-stream wetland did provide DP retention.
      During other time periods, DP was released due to changes in wetland area,
      rainfall, and DP concentrations.

PMID- 14964397
TI  - Alum treatment of poultry litter: decomposition and nitrogen dynamics.
AB  - While the poultry industry is a major economic benefit to several areas in the
      USA, land application of poultry litter to recycle nutrients can lead to impaired
      surface and ground water quality. Amending poultry litter with alum [Al3(SO4)2 x
      14H2O] has received considerable attention as a method of economically reducing
      ammonia volatilization in the poultry house and soluble phosphorus in runoff
      waters. The objective of this study was to characterize the effect of alum on
      broiler litter decomposition and N dynamics under laboratory conditions. Litter
      that had been amended with alum in the poultry house after each of the first four
      of five flock cycles (Experiment I) and litter that had been amended with alum
      after removal from a poultry house after the third flock cycle (Experiment II)
      were compared with unamended litter in separate studies. The litters in
      Experiment I were surface-applied to simulate application to grasslands, while
      the litters in Experiment II were incorporated to simulate application to
      conventionally tilled crops. The only statistically significant differences in
      decomposition due to alum occurred early in Experiment II and the differences
      were small. The only statistically significant differences in net N
      mineralization, soil inorganic N, and soil NH4+-N in either experiment was found
      in Experiment I after 70 d of incubation where soil inorganic N was significantly
      greater for the alum treatment. Thus, alum had little effect on decomposition or
      N dynamics. Results of many of the studies on litter not amended with alum should
      be applicable to litters amended with alum to reduce P availability.

PMID- 14964398
TI  - A simple high performance liquid chromatography method for analyzing paraquat in
      soil solution samples.
AB  - A high performance liquid chromatography (HPLC) method with UV detection was
      developed to analyze paraquat (1,1'-dimethyl-4,4'-dipyridinium dichloride)
      herbicide content in soil solution samples. The analytical method was compared
      with the liquid scintillation counting (LSC) method using 14C-paraquat. Agreement
      obtained between the two methods was reasonable. However, the detection limit for
      paraquat analysis was 0.5 mg L(-1) by the HPLC method and 0.05 mg L(-1) by the
      LSC method. The LSC method was, therefore, 10 times more precise than the HPLC
      method for solution concentrations less than 1 mg L(-1). In spite of the high
      detection limit, the UC (nonradioactive) HPLC method provides an inexpensive and
      environmentally safe means for determining paraquat concentration in soil
      solution compared with the 14C-LSC method.

PMID- 14964399
TI  - Analysis of the distribution and genetic variability of viral isolates in a
      cohort of HCV-positive hepatopathic patients.
AB  - The genotyping of the hepatitis C virus (HCV) by viral nucleic acids sequencing
      allows accurate epidemiological evaluation of a cohort of patients suffering from
      HCV-related chronic hepatopathy. The identification of viral isolates, which can
      be generally associated with hepatic damage or, vice versa, which are more
      responsive to pharmacological treatment, might enhance clinical interest on the
      nature of the infecting genotypes. We, therefore, draw attention to those viral
      genotypes that are characterised by significantly high or altered viremic and
      enzymatic levels.

PMID- 14964400
TI  - Once-daily saquinavir and ritonavir in treatment-experienced HIV-1-infected
      individuals.
AB  - To assess the efficacy of 48 weeks' treatment with saquinavir 1600 mg and
      ritonavir 100 mg, both given once daily (SQVOD), in drug-experienced HIV-infected
      patients, a SQVOD-based therapy was offered to 100 treatment-experienced patients
      via their own physicians. The patients starting this regimen were followed up for
      48 weeks. HIV-RNA was assessed by means of NASBA (limit of quantification = 80
      copies/mL). Fifteen patients received the SQVOD-based therapy. Six discontinued
      before week 48 because of failure, toxicity or intolerance due to the high pill
      burden and gastrointestinal side effects. The median baseline CD4+ cell counts
      and plasma HIV-RNA levels were 317 cells/microL (range 44-698) and 4.18 log
      copies/mL (range 2.65-6.18). At week 4, there was a mean decrease of 1.96 log
      copies/mL (P < 0.0001) in HIV-RNA, with 75% of the patients having fewer than 400
      copies/mL; seven of the nine patients treated for 48 weeks reached fewer than 400
      copies/mL. No substantial change in cholesterol or triglyceride values was
      observed over 48 weeks. As this SQVOD-based regimen had considerable short-term
      virologic activity in treatment-experienced HIV-infected patients, it may be a
      reasonable option when non-nucleoside reverse transcriptase inhibitors cannot be
      administered and once-daily dosing is preferred by the patient. However, the high
      pill burden and frequent gastrointestinal side effects of the soft gel capsule
      formulation of saquinavir may limit its long-term efficacy.

PMID- 14964401
TI  - Use of IgG Avidity test in case definitions of toxoplasmosis in pregnancy.
AB  - A survey network for congenital toxoplasmosis (TOXO-NET) was set up in December
      1996 in Piedmont (Italy). Participants were asked to classify the infections in
      pregnant mothers and newborns by the criteria of the European Network on
      Congenital Toxoplasmosis published by Lebech in 1996. Because the IgG Avidity
      test is largely employed as a 2nd level test in toxoplasmosis diagnosis and it
      could be helpful to date infection, the co-ordinators of TOXO-NET suggested
      including it in the "case definition" of "probable" infection and "unlikely"
      infection. 117 cases of toxoplasmosis in pregnancy divided into the risk
      categories under Lebech's criteria were re-examined using the "new" case
      definitions. 77 out of 117 (65.8%) Toxoplasma gondii infections during pregnancy
      could be defined with only one serum sample using the IgG Avidity test. The IgG
      Avidity test proved a useful method to classify the Toxoplasma gondii infections
      in pregnancy, especially when we had only one serum sample.

PMID- 14964402
TI  - Annual trends in antibiotic resistance of nosocomial Acinetobacter baumannii
      strains and the effect of synergistic antibiotic combinations.
AB  - Acinetobacter baumannii is becoming increasingly resistant to antibiotics often
      requiring combination therapy. Annual changes of resistance to selected
      antimicrobials of 150 A. baumannii strains, isolated as nosocomial pathogens
      between 1994 and 2000 were investigated. The synergistic effects of
      antimicrobials were studied using a microdilution checkerboard technique in eight
      selected isolates resistant to third-generation cephalosporins and beta
      lactam/beta-lactamase inhibitor combinations and to at least one aminoglycoside.
      Rates of resistance of cefepime, ceftazidime, ampicillin/sulbactam, amikacin and
      ciprofloxacin (before 1996 and between 1996-2000) were 29.7% - 72.6, 37.8% -
      81.4%, 35.1% - 72.6%, 8.1% - 56.6%, 5.4% - 46.0% respectively (p < 0.001 for each
      one). Synergy was observed in at least one of the combinations of antibiotics
      from seven of eight isolates (87%), no antagonism was detected with any
      combination. Ceftazidime-amikacin (50%) and ampicillin/sulbactam-tobramycin (50%)
      were the most effective combinations. Due to the effectiveness of sulbactams to
      Acinetobacter, ampicillin/sulbactam-tobramycin combination is recommended as the
      first line of choice.

PMID- 14964403
TI  - Population dynamics in ageing Helicobacter pylori.
AB  - The aim of this work was to characterize population changes occurring in aged
      broth cultures of Helicobacter pylori. Experiments were performed using clinical
      strains cultured immediately after isolation and after multiple subcultures in
      solid medium. Morphological changes in the ageing bacteria during a 7-day broth
      culture were analysed by optical and electron microscopy. The expression of the
      virulence factor, CagA, together with the presence of the cell cycle regulator,
      cGMP, were also assessed. The transition from bacillary to coccoid forms was the
      main morphological change observed in freshly isolated bacteria, together with
      the increase in cGMP from 1 to 2.25 nmoles/mg of proteins within the first 7 days
      of broth culture. A similar trend of morphological and physiological changes was
      observed in cells after multiple subcultures in solid medium with a major
      presence of large cell clusters. The cagA gene product was always expressed in
      all experimental conditions evaluated. These data show a significant
      morphological and physiological diversity in fresh, ageing and aged cultures of
      H. pylori.

PMID- 14964404
TI  - Bloody diarrhoea cases caused by Shigella and amoeba in Jordan.
AB  - This study was done to evaluate the occurrence of bloody diarrhoea in Jordan in
      the period 1988-2000, with particular interest in Shigilla and amoeba cases in
      relation to the surveillance control system and hygiene policy. The cases were
      collected from various medical diagnostic laboratories. In addition to the
      clinical presentation, stool specimens or rectal swabs were collected and sub
      cultured on the appropriate media. Shigella spp. and amoeba were identified using
      standard methods. Anti-microbial susceptibility tests were performed. One-way
      ANOVA and Least Significant Difference (LSD) were used for statistical analysis.
      The number of stool specimens tested for bloody diarrhoea was 34,529 in the study
      period. Positive stool samples were reported in 711 (2.1%) patients. Out of these
      55% were males and 45 % were females. The highest number of cases 96 (13.5%) was
      reported in the year 1999. The highest incidence rate was (20.6) in the year 1996
      and the lowest incidence rate (8.9) was in the year 2000. The highest number of
      cases during the period 1998-1992 was among age group 1-4 year. During the year
      1993-1996 the highest number of cases was among group 5-14 year. The highest
      number of cases during the year 1997-2000 was among age group 15-24 year. There
      was a significant variation between numbers of bloody diarrhoeal cases and age
      groups (P < 0.001) as well as sex (P = 0.028). No significant variation (P =
      0.06) was observed between number of bloody diarrhoea cases and seasons or
      months. The number of stool specimens tested for amoebiasis during the study
      period 1994-2000 was 229,040. Shigella was isolated from 304(0.13%) cases and
      amoeba was found in 24,211(10.6%) cases. The lowest incidence rate in bloody
      diarrhoeal cases in the year 2000 indicates good quality hygienic control. The
      increased resistance of Shigella to antibiotics may produce a future problem,
      which might require a further prescribing policy for treatment.

PMID- 14964405
TI  - Non tuberculous mycobacteria (NTM) in patients with underlying diseases: results
      obtained by using polymerase chain reaction-restriction enzyme analysis between
      1997-2002.
AB  - In this study, we aimed to evaluate the frequency of non-tuberculous mycobacteria
      (NTM) isolated from clinical specimens using Polymerase Chain Reaction
      Restriction Enzyme Analysis (PCR-REA) and to investigate the patients who had
      clinically significant NTM infections in our hospital through the five year
      period from May 1997 to June 2002. A total of 364 mycobacterial strains isolated
      from clinical specimens which gave positive growth index in the BACTEC 460
      radiometric system in Hacettepe University Hospital Clinical Microbiology
      Laboratory were evaluated by PCR-REA and clinical data were obtained from the
      patient records. Three hundred and one of the strains (82.7%) were identified as
      Mycobacterium tuberculosis and 63 (17.3%) were identified as nontuberculous
      mycobacteria. Seven (11.1%) of 63 NTM patients were regarded as having clinical
      mycobacteriosis. Chronic obstructive pulmonary disease and other pre-existing
      lung diseases were seen in 39 (61.9%) of the patients, 11 (17.5%) of'the patients
      had chronic renal failure. Four (6.3%) and 9 (14.3%) of them had AIDS and
      carcinomas, respectively. PCR-REA was found to be a reliable method for typing of
      our mycobacterial isolates to the species level. These data may shed light on the
      epidemiology of the mycobacterial species and help to select a proper treatment
      regimen.

PMID- 14964406
TI  - Microbiological study and scanning electron microscopic analysis of root canal
      wall dentin following pumped Diodium Nd:YAG laser irradiation.
AB  - The capability of Nd:YAG laser in sterilizing root canals and the alterations of
      dentinal walls induced by laser treatment were investigated. Thirty root canals
      were infected by P. aeruginosa ATCC 27853 and thirty canals by A. naeslundii CH
      12. Within each infection, 4 groups were selected on the basis of the treatment.
      Among them, 2 test groups (TGs) were treated by Nd:YAG laser at 15 Hz for 15 s,
      using 2 different settings: 1 Watt/70 Joule and 1.5 Watt/100 Joule, respectively
      (n = 10 each). The other 2 groups, used as controls (CGs), were: untreated
      (positive control, n = 5) and sterilized by 5.25% NaClO group (negative control,
      n = 5). Observations under scanning electron microscope (SEM) and quantitative
      bacterial counts were performed. These analyses were performed once per group
      after infections and treatments. Laser treatments significantly reduced the
      number of both bacteria. SEM investigation showed melting and crystallization of
      canal dentin over 1.5 W/100 J. Laser irradiation has a bactericidal effect but it
      does not completely sterilize the root canal as NaClO 5.25% solution does if the
      goal of treatment is also to avoid alterations of dentinal walls.

PMID- 14964407
TI  - Identification of human papilloma viruses in male dysplastic genital lesions.
AB  - The association of Human Papillomaviruses (HPV) DNA with female genital lesions
      has been widely documented whereas little has been reported about male genital
      pathologies. The aim of this work was to investigate the presence of HPV DNA and
      the genotype involved in male dysplastic genital lesions. All samples were
      analysed by polymerase chain reaction (PCR) to amplify HPV E1 and L1 genes. The
      PCR products were subjected to restriction fragment length polymorphism (RFLP) to
      determine the HPV genotype. We analysed 209 male genital biopsies from different
      lesions: mostly from acuminate condylomata and from Buschke-Lowenstein tumours,
      Bowen papulosis, leukoplakia of the glans, scrotal lymphangioma, penile horn and
      penile/perianal verrucous carcinoma. Our results revealed the constant presence
      of viral DNA in genital condylomata, mainly associated with low risk HPV; the
      presence of the same genotypes was also detected in some of the examined rare
      pathologies.

PMID- 14964408
TI  - In vitro productive infection of non polarised cervical and rectal biopsies by
      syncytium-inducing and non syncytium inducing primary HIV-1 isolates.
AB  - An in vitro model was used to study the transmission of HIV-1 primary isolates
      with different biological phenotype to cervical and rectal non polarised bioptic
      fragments. The method described allowed the productive infection of both cervical
      and rectal tissues and the virus produced could be propagated onto peripheral
      blood mononuclear cell cultures. Syncytium-inducing and non-syncytium inducing
      viral isolates were equally able to produce infection and replication.

PMID- 14964409
TI  - Mycobacterium avium sub. paratuberculosis in tissue samples of Crohn's disease
      patients.
AB  - Crohn's disease is a non-specific chronic transmural inflammatory disease. The
      disease was associated with a frameshit mutation in the NOD2 gene. Nevertheless,
      other researchers associated the presence of M. paratuberculosis within the
      intestinal tissues of patients with the disease. An adapted "in situ
      hybridization" technique was used to detect IS900 M. paratuberculosis DNA in
      paraffin embedded tissue from Crohns tissue disease samples. We were able to
      identify M. paratuberculosis DNA in around 69% of the paraffine embedded
      intestinal samples of Crohn's disease patients analysed. The presence of M.
      paratuberculosis DNA in the intestinal samples analysed does not necessarily mean
      that M. paratuberculosis is responsible for Crohn's disease. Our results support
      the hypothesis that infection may be caused by cell wall defective M.
      paratuberculosis since no bacteria were detected by Ziehl Neelsen stain.

PMID- 14964410
TI  - A severe dual infection by feline panleukopenia virus and feline calicivirus in
      an adult cat.
AB  - A dual infection by feline panleukopenia virus (FPV) and feline calicivirus (FCV)
      in a 7 month-old cat is described. The animal developed a severe illness with
      depression, anorexia, fever, leucopoenia, nasal and ocular discharge and oral
      ulcers. Both FPV and FCV were isolated in cell cultures from a rectal swab and
      the presence of FCV was confimed by polymerase chain reaction. Antibodies to both
      the viruses were detected in the serum. The severity of the disease induced by
      the mixed viral infection highlights the need for intensifying FPV vaccination in
      cats.

PMID- 14964411
TI  - Inhibitory effect of water-soluble chitosan on growth of Streptococcus mutans.
AB  - The present study was undertaken to evaluate the effects of pH and the degree of
      polymerization of chitosan on the inhibition of growth of Streptococcus mutans.
      Three types of chitosan, polymer, oligomer and monomer, were used at 4% (W/V) and
      three different levels of pH: 6.0, 6.5 and 7.4. Bactericidal activity was
      calculated by the growth ratio. Chitosan oligomer significantly inhibited
      bacterial growth at a pH value of 6.5. All three types of chitosan strongly
      inhibited bacterial growth at pH 6.0. Furthermore, nearly complete inhibition was
      obtained with 2%(W/V) chitosan solution at constant pH 6.5. This study is the
      first to report that water-soluble chitosan directly suppresses the growth of the
      typical cariogenic bacterium S. mutans even at pH 6.5, without causing
      demineralization of the tooth surface.

PMID- 14964412
TI  - Rickettsial disease: classical and modern aspects.
AB  - Rickettsial diseases have been reassessed in recent years since they represent an
      important field in today's medicine. New agents have been described: some are non
      pathogenic agents and the others are associated with well-defined or peculiar
      clinical patterns. In addition, different species of rickettsiosis are found in
      relation to the geographic areas of the world. Some agents may be defined as
      variants of older diseases whereas most of the newly described forms of
      rickettsiosis represent distinct entities with unique epidemiologial and clinical
      features. Probably the main news regards the group of the spotted fevers. An
      additional new aspect is linked to the medicine of travellers and tourists.
      However, this aspect may not be significant for the rickettsial diseases in
      relation to other human illnesses, such as malaria. Therefore, an investigation
      into the geographical origin of patients has to enter our routine medical work.

PMID- 14964413
TI  - Nanosuspensions as the most promising approach in nanoparticulate drug delivery
      systems.
AB  - Over the years, controlled drug delivery as well as site-specific delivery have
      made considerable advances. One area that contributed significantly to this
      progress is the rapidly developing field of colloidal drug delivery systems.
      Nanoparticles, one of the colloidal drug delivery systems, may enable new
      possibilities for therapy that presently have not been investigated. Recent
      advances in nanoparticle research are discussed here. The present review
      highlights new and upcoming developments such as nanosuspensions and solid lipid
      nanoparticles.

PMID- 14964414
TI  - Mechanism and kinetics of synthesis of allicin.
AB  - Allicin, allyl-thiosulfinate, a pharmacologically active compound with
      considerable fungicidal, bactericidal, antioxidant and anticarcinogenic effects,
      was obtained by oxidizing allyl disulfide with acid hydrogen peroxide. The
      synthesis mechanism was studied by the ESR spin trap method. The kinetics of
      allicin synthesis was ascertained by determination of the concentration of the
      limiting reactant during the synthesis using HPLC and it was found that the
      allicin synthesis reaction was of zero order. The allicin obtained was determined
      using UV, FT-IR, MS, 1H and 13C NMR analysis.

PMID- 14964415
TI  - [Benzo[c][2,7]naphthyridines from 2,6-dinor-nifedipine and its dimethyl 2,5
      dicarboxylate isomer].
AB  - The reaction of 2-nitrobenzaldehyde with methyl propiolate and ammonium acetate
      in acetic acid yields 2,6-dinor-nifedipine (1a) and the isomeric rac. 1,4
      dihydropyridine (DHP) 1b. The DHP 1 are dehydrogenated both chemically and by
      anodic oxidation using a rotating platinum electrode (RPE) by means of
      differential pulse voltammetry (DPV) affording the corresponding pyridines 2a, b.
      Compound 1a is more stable, while compound 1b is less stable than nifedipine.
      Irradiation of the DHP 1 with UV-A light forms the nitrosophenyl-pyridines 3,
      which cyclize after addition of conc. hydrochloric acid to yield the chloro
      substituted hydroxamic acids 4a, b. The hydroxamic acids 4c, d are obtained
      treating 2a, b with zinc in acetate buffer pH 4.6. The hydroxamic acids 4b, d
      demonstrate only a moderate inhibition of 5-lipoxygenase (5-LOX) of human whole
      blood compared with the activity of the reference compound zileutone. The
      formation of 15-HETE is also inhibited. Compound 4a reduces the activity of
      cyclooxygenase. The lactames 5, obtained from the hydroxamic acids 4 by
      desoxygenation with phosphorus trichloride, react with phosphoryl chloride to
      give compounds 6, representing educts for potential agents against malaria.

PMID- 14964416
TI  - Liquid chromatographic-mass spectrometric method for quantitative determination
      of lisinopril in human plasma.
AB  - A validated liquid chromatographic-mass spectrometric (LC/MS) method for the
      determination of lisinopril in human plasma is presented. Enalapril was used as
      an internal standard. After the addition of internal standard, solid phase
      extraction was used as a cleaning step. To separate lisinopril and enalapril from
      interfering endogenous plasma substances, the analysis was performed using column
      switching valve. The quantitative determination was performed using selected ion
      monitoring (+)-electrospray LC-MS. A combination of an acidic mobile phase and a
      reverse phase column was used. A precision in the linear range from 10 to 500.0
      ng/mL plasma, absolute recovery of 91.69% for lisinopril and 90.26% for
      enalapril, stability for 3.5 months at -20 degrees C have been achieved. Limit of
      quantitation (LOQ) was 10 ng/mL while limit of detection (LOD) was about 1 ng/mL.

PMID- 14964417
TI  - Preparation of solid drug/cyclodextrin complexes of acidic and basic drugs.
AB  - One of the main obstacles in pharmaceutical applications of cyclodextrins is
      their increase of the formulation bulk. Even at maximum incorporation 500 mg of a
      solid drug/cyclodextrin complex will only contain between 50 and 125 mg of the
      drug, assuming a low molecular weight drug (MW 200 to 400 Dalton) and an average
      molecular weight cyclodextrin (MW about 1500 Dalton). In general, the
      complexation efficiency is low and consequently the complex powder contains a
      significant amount of empty cyclodextrin molecules. In the present study the
      complexation efficiency is increased by ionization of the drug molecule through
      addition of volatile acid (i.e. acetic acid) or base (i.e. ammonia) to the
      aqueous complexation media of basic or acidic drugs, respectively. The volatile
      acid or base was then removed during lyophilization and heating in a vacuum oven
      resulting in formation of solid cyclodextrin complexes of the unionized drug.
      Thus, the complexation efficiency was temporary increased by the ionization but
      then again decreased leading to formation of the thermodynamically unstable solid
      drug/cyclodextrin complexes. When dissolved the energy of the system was lowered
      by expelling the drug molecules from the cyclodextrin cavities resulting in
      formation of supersaturated drug solutions and ultimately precipitation of the
      drug.

PMID- 14964418
TI  - Influence of cyclodextrin complexation on the photodegradation and antioxidant
      activity of alpha-tocopherol.
AB  - The influence of complexation with beta-cyclodextrin (beta-CD), hydroxypropyl
      beta-cyclodextrin (HP-beta-CD) or hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD)
      on the antioxidant activity and light-induced decomposition of vitamin E (alpha
      tocopherol) was investigated. The interaction of the vitamin with the
      cyclodextrins was ascertained by nuclear magnetic resonance spectroscopy. The
      photodegradation of alpha-tocopherol was examined in emulsion vehicles and was
      not significantly influenced by complexation with beta-CD (the extent of
      decomposition was 39.9% for the beta-CD complex compared to 47.2% for the free
      vitamin) whereas HP-beta-CD and HP-gamma-CD enhanced the light-induced
      decomposition of alpha-tocopherol (the loss of the vitamin reached 64.6% for the
      HP-beta-CD complex and 65.8% for the HP-gamma-CD complex). On the other hand,
      accelerated stability studies indicated that the degradation of non-irradiated
      alpha-tocopherol was reduced by complexation with HP-beta-CD or HP-gamma-CD. The
      radical scavenging activity of alpha-tocopherol was evaluated in vitro using the
      xanthine/xanthine oxidase enzymatic system. No significant differences were
      observed between the free form of the vitamin and its complexes with beta-CD, HP
      beta-CD or HP-gamma-CD. Therefore, complexation of alpha-tocopherol with these
      cyclodextrins does not interfere with the vitamin antioxidant activity.

PMID- 14964419
TI  - Standardisation and physicochemical characterisation of the extracts of seeds of
      Glinus lotoides.
AB  - Extraction methods were standardised for saponin-containing extracts from the
      seeds of Glinus lotoides and the effects of some extraction process variables,
      such as the extracting solvent (various concentrations of methanol in water) and
      method of extract drying (freeze-drying and vacuum oven-drying), on the physical
      properties of the extracts were investigated. Physicochemical properties, namely
      particle size and size distribution, morphology, water uptake profiles and
      sorption isotherms, densities, flow properties and compaction profiles, of the
      crude dry extracts of 60% methanol (extract A), 70% methanol (extract B) and 80%
      methanol (extract C) were investigated. The average particle sizes (X50) of
      extracts A, B and C were found to be 68.4, 92.1 and 68.5 microm, respectively.
      Scanning electron micrographs of freeze-dried and vacuum oven-dried extract A
      showed that the particles are irregular in shape and are compact masses with
      sharp edges. The percent water uptake by the crude extracts was found to increase
      with an increase in relative humidities, while the hygroscopicity increased with
      decreasing methanol ratio of the extracting solvent. The bulk and the true
      densities of the three extracts (A, B and C) ranged from 0.66 to 0.67 and 1.49 to
      1.50 g/ml, respectively. The tapped density (0.94 g/ml) and hence the porosity
      (56.0%), Carr's index (29.8%) and Hausner ratio (1.42) of extract A were greater
      than those of extracts B and C. Measurements of angle of repose indicated that
      all of the extracts exhibit poor flow properties. Compaction studies revealed
      that extract C has higher compactibility than extracts A and B.

PMID- 14964420
TI  - Effect of penetration enhancers on in vitro percutaneous penetration of
      nimesulide through rat skin.
AB  - The influence of several penetration enhancers alone and/or in various
      combinations on the percutaneous penetration of nimesulide (NM) from Carbopol 934
      based gel formulations was investigated. Skin permeation studies were performed
      using Franz-type diffusion cells and full-thickness abdominal rat skin. Various
      types of compounds such as ethanol, isopropyl alcohol, propylene glycol,
      Transcutol, Tween 80 and oleic acid were employed as penetration enhancers. The
      steady-state flux, the lag time and permeability coefficients of NM for each
      formulation were calculated. The results showed that the skin permeability of NM
      from gels tested was significantly increased (P < 0.05) by isopropyl alcohol
      (40%) and the combination of oleic acid (3%) with Transcutol (30%) when compared
      with the control formulation. In conclusion, these substances could be considered
      as penetration enhancers for NM topical formulations.

PMID- 14964421
TI  - Apoptosis induction by 4beta-acetoxyscirpendiol from Paecilomyces tenuipes in
      human leukaemia cell lines.
AB  - The carpophores of Paecilomyces tenuipes are known in the Orient for their strong
      antitumor activity. In continuation of our study on acetoxyscirpendiol (ASD,
      4beta-acetoxyscirpene-3alpha,15-diol) as a cytotoxic component from this fungus,
      we report particularly on the mode of action of ASD in inducing apoptosis in
      human MOLT-4, THP-1 and Jurkat T cell leukaemia in vitro. The antiproliferative
      effects of ASD seem attributable to its induction of apoptosis in the cells, as
      it blocked the cell cycle, induced hypodiploidity and bound annexin V and also
      cleaved poly-(ADP-ribose) polymerase (PARP) in these cell lines. The 50%
      inhibitory concentrations (IC50) of ASD on MOLT-4, THP-1 and Jurkat T cells were
      found to be 60, 85 and 60 ng/ml, respectively. ASD arrested the cell cycle at the
      G1/S transition and showed hypodiploidity due to the accumulation of sub-G0
      population. Annexin V binding was increased in the presence of ASD in the MOLT-4
      cell line in a time-dependent manner. ASD and three of its derivatives also
      induced cleavage of PARP in both MOLT-4 and Jurkat T cell lines. From these data,
      it is suggested that ASD exerts its cytotoxic activity by inducing apoptosis in
      leukaemia cell lines in vitro.

PMID- 14964422
TI  - Effect of cutaneously applied nonionic surfactants and local anesthetic bases on
      thermal sensations.
AB  - With cutaneously applied local anesthetic bases various effects may be observed,
      such as a decrease in pricking pain and a change in burning, itch, and thermal
      sensations. These effects occur after skin penetration and may be attributed to
      the action of the anesthetics on nociceptors and thermoreceptors, i.e., on C and
      A delta nerve fibers, respectively. As little is known about the pharmacodynamic
      response of nonionic surfactants with a potentially anesthetic action such as
      polidocanol, this study characterizes nonionic surfactants pharmacodynamically by
      measuring thermal thresholds with a thermal sensory analyzer after cutaneous
      application. The results obtained with the nonionic surfactants were compared
      with data resulting from the cutaneous application of local anesthetic bases such
      as mepivacaine, bupivacaine, prilocaine, lidocaine, the 1:1 mixture of lidocaine
      and prilocaine contained in EMLA and a triple mixture consisting of lidocaine,
      prilocaine and tetracaine (1:1:1). The results show that none of the investigated
      surfactants affect thermal thresholds probably due to their high molecular
      weight. The same was observed with the anesthetics mepivacaine and bupivacaine.
      In contrast, prilocaine, lidocaine, the 1:1 mixture of lidocaine and prilocaine
      and the triple mixture consisting of lidocaine, prilocaine and tetracaine (1:1:1)
      proved to be potent local anesthetics. However, their pharmacodynamic responses
      do not differ significantly from each other.

PMID- 14964423
TI  - Effect of glycine on oxidative stress in rats with alcohol induced liver injury.
AB  - We studied the effect of administering glycine on tissue lipid peroxidation and
      enzymic and non-enzymic antioxidants in experimental hepatotoxic Wistar rats.
      Hepatotoxicity was induced by administering ethanol for 30 days by intragastric
      intubation. Glycine administered at a dose of 0.6 g kg(-1) body weight for 30
      days significantly inhibited the severe oxidative stress as evidenced by the
      decreased levels of liver and brain thiobarbituric acid reactive substances
      (TBARS) and hydroperoxides compared to control. The activities of enzymic and non
      enzymic antioxidants such as reduced glutathione (GSH), glutathione peroxidase
      (GPx), superoxide dismutase (SOD) and catalase (CAT) in the liver and brain were
      significantly elevated on glycine supplementation as compared to the untreated
      alcohol fed rats. The levels of serum vitamin E and vitamin C were also increased
      to near normal levels on glycine treatment. Microscopic examination of alcohol
      treated rat liver showed inflammatory cell infiltrates and fatty changes, which
      were alleviated on treatment with glycine. Alcohol treated rat brain demonstrated
      oedma, which was significantly lowered on treatment with glycine. Thus our study
      shows that administering glycine to alcohol supplemented rats, markedly reduced
      the oxidative stress and elevated the enzymic and non-enzymic antioxidants in the
      liver and brain, which a was associated with a reversal of hepatic steatosis and
      cerebral oedma.

PMID- 14964424
TI  - The serum of rats administered flavonoid extract from Epimedium sagittatum but
      not the extract itself enhances the development of rat calvarial osteoblast-like
      cells in vitro.
AB  - The flavonoid extract from Epimedium sagittatum (FES) has been found by us to be
      effective in preventing osteoporosis induced by ovariectomy in rats. In the
      present study, the effect of FES on the development of rat calvarial osteoblast
      like (ROB) cells was investigated. No appreciable effect was observed when ROB
      cells were exposed to FES in vitro. However, serum isolated from rats
      administered FES orally was able to significantly stimulate the proliferation as
      well as the osteoblastic differentiation of ROB cells compared to serum from
      control rats. The results indicate that the serum of rats administered FES
      contains active metabolites ofFES that enhance the development of osteoblasts,
      while the original form of FES itself is inactive.

PMID- 14964425
TI  - Proteomic signatures for daunomycin and adriamycin in Bacillus subtilis.
AB  - The influence of the two anthracyclin antibiotics daunomycin and adriamycin on
      the proteome of Bacillus subtilis was investigated. They intercalate in the
      double helix causing strand breaks. Both compounds induce proteins related to DNA
      damage and oxidative stress as indicated by the induction of some members of the
      PerR and the DinR-regulon. The mild induction of some members of the HrcA- and
      the CtsR-regulon may indicate protein oxidation as well. Furthermore, an
      influence on the sigmaB-dependent general stress response was shown. These data
      show that the proteomic signature is a valuable experimental tool for a
      comprehensive evaluation of the action of different drugs.

PMID- 14964426
TI  - Quantitative determination of rofecoxib in pharmaceutical preparations.
AB  - Rofecoxib was assayed by UV spectrophotometry and HPLC, the concentration ranges
      were 2-30 microg x ml(-1) and 5-50 microg x ml(-1), respectively. The results,
      obtained by the two methods in pharmaceutical preparations were compared of each
      other. There were no significant differences between the mean values and the
      precisions.

PMID- 14964427
TI  - [Glycine determination according to the European Pharmacopoeia].
AB  - The treatment of an aqueous solution of glycine with hypochlorite yields
      formaldehyde and glyoxylic acid. After acidification and removing formaldehyde by
      boiling glyoxylic acid reacts with resorcinol to the lactone of bis-2,4
      dihydroxyphenyl acetic acid. Under alkaline conditions the lactone is oxidized to
      the violet oxonol anion and subsequently, after hydrolysis of the lactone, to the
      yellow fluorescent carboxylate anion.

PMID- 14964428
TI  - Use of electrolyte induced flocculation technique for an in vitro steric
      stability study of steric stabilized liposome formulations.

PMID- 14964429
TI  - Onset and offset pharmacodynamics of propofol.
AB  - Propofol whole blood and plasma concentrations at offset of hypnosis in eighteen
      patients were inversely related to patient age and body fat. The relationship
      between propofol concentrations and body fat is derived from the relationship
      between age and body fat and age was the single independent predictor of
      concentrations at offset of propofol hypnosis.

PMID- 14964430
TI  - Antiproliferative effects of abietane diterpenoids isolated from Hyptis martiusii
      Benth (Labiatae).
AB  - Two abietane diterpenes were isolated from a hexane extract of Hyptis martiusii
      roots and identified as carnasol 11,14-dihidroxy-8,11,13-abietatrien-7-one. These
      compounds were tested for their antiproliferative effects on tumor cell lines
      using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and on the
      sea urchin egg development. Both compounds displayed cytotoxic activity against
      tumor cell lines, but only carnasol was able to inhibit the sea urchin egg
      cleavages.

PMID- 14964431
TI  - Human GH pulsatility: an ensemble property regulated by age and gender.
AB  - Age and gender impact the full repertoire of neurohormone systems, including most
      prominently the somatotropic, gonadotropic and lactotropic axes. For example,
      daily GH production is approximately 2-fold higher in young women than men and
      varies by 20-fold by sexual developmental status and age. Deconvolution estimates
      of 24-h GH secretion rates exceed 1200 microg/m2 in adolescents and fall below 60
      microg/m2 in aged individuals. The present overview highlights plausible factors
      driving such lifetime variations in GH availability, i.e., estrogen, aromatizable
      androgen, hypothalamic peptides and negative feedback by GH and IGF-I. In view of
      the daunting complexity of potential neuromodulatory signals, we underline the
      utility of conceptualizing a simplified three-peptide regulatory ensemble of
      GHRH, GHRP (ghrelin) and somatostatin. The foregoing signals act as individual
      and conjoint mediators of adaptive GH control. Regulation is enforced at 3-fold
      complementary time scales, which embrace pulsatile (burst-like), entropic
      (orderly) and 24-h rhythmic (nycthemeral) modes of GH release. This unifying
      platform offers a convergent perspective of multivalent control of GH outflow.

PMID- 14964432
TI  - Regulation of body composition by androgens.
AB  - Human body can be viewed simplistically as being composed of fat-free and fat
      mass. With more sophisticated techniques, body composition can be broken down
      into fat mass, skeletal muscle mass, nonmuscle lean mass, visceral mass and bone
      mineral content. Similarly, it is possible to obtain estimates of total body
      water and intracellular and extracellular water contents. Regardless of the model
      of body composition assessment, it is evident that androgens are important
      determinants of body composition; there is no body compartment that is not
      directly or indirectly affected by androgens. The effects of androgens on
      skeletal muscle mass have received the greatest attention in recent literature;
      however, growing body of evidence suggests that androgens also regulate fat mass,
      bone mineral content, nonmuscle soft tissues and body water.

PMID- 14964433
TI  - Effects of GH and insulin-like growth factor-I on body composition.
AB  - In this review, different methods to estimate body composition are discussed
      shortly. The effects by GH on total and visceral fat mass, lean mass, muscle
      strength and body water are described. Gender differences in the sensitivity to
      GH administration are reviewed. Finally, a short description of the effects of
      insulin-like growth factor-I (IGF-I) administration on body composition has been
      included.

PMID- 14964434
TI  - Erythropoietin.
AB  - This article summarizes recent advances in understanding the production and
      action of the hormone erythropoietin (Epo) with respect to high altitude
      physiology and sports medicine. Hypoxia is the main stimulus for Epo gene
      expression. An O2-labile protein (hypoxia-inducible factor 1, HIF-1) has been
      identified that is hydroxylated and degraded under normoxic conditions but active
      in hypoxia, where it enhances Epo gene transcription resulting in elevated
      hemoglobin levels and O2 capacity of the blood. The stimulation of Epo production
      at lowered arterial O2 tension can be maladaptive, if erythrocytosis develops
      such as seen in high altitude habitants. Within physiological limits the aerobic
      power increases in parallel with blood O2 capacity. Therefore, some elite
      athletes have misused recombinant human Epo (rhEpo), which is a beneficial anti
      anemic drug in clinical practice. Indirect and direct methods to detect rhEpo
      doping have been recently developed.

PMID- 14964435
TI  - Exercise, hormones, and body temperature. regulation and action of GH during
      exercise.
AB  - That physical exercise stimulates pituitary GH secretion has been known for forty
      years, but the underlying mechanisms as well as the physiological significance
      remain elusive. We have previously shown that the concomitant increase in core
      temperature is essential for the exercise-induced GH release, inasmuch as
      exercise performed at 4 C results in a suppression of GH secretion, whereas
      passive heating constitutes a potent stimulus for GH release. Moreover, studies
      in normal subjects show that GH stimulates sweat production and evaporative heat
      loss during heat exposure with and without exercise, whereas GH-deficiency is
      associated with reduced sweat secretion and increased heat storage during similar
      conditions. The neurotransmitters involved in GH secretion during exercise remain
      uncertain; we therefore investigated the putative role of ghrelin, which is a gut
      derived endogenous ligand for the GHS receptor. We measured circulating ghrelin
      levels before during and after submaximal aerobic exercise in healthy subjects
      and GH-deficient patients. The circulating ghrelin levels were unchanged during
      and after exercise in all subjects. Growth hormone stimulates lipolysis and lipid
      oxidation during basal and fasting conditions and we recently investigated
      whether GH also regulates substrate metabolism during exercise. The design
      involved GH-deficient patients studied during exercise with and without GH
      administration as compared to untreated healthy subjects. Growth hormone
      predominantly stimulated the turnover of free fatty acids in the recovery phase
      after exercise. CONCLUSIONS: 1) the increase in GH release during exercise is
      associated with the concomitant increase in body temperature, 2) GH stimulates
      sweat secretion and heat evaporation during exercise, which seems to be of
      distinct physiological significance, 3) ghrelin is not involved in exercise
      induced GH release, 4) the impact of GH on substrate metabolism during exercise
      includes increased FFA turnover.

PMID- 14964436
TI  - Neuroendocrine control of GH release during acute aerobic exercise.
AB  - GH secretion declines with aging and is decreased in conditions such as obesity.
      Several physiologic factors alter pulsatile GH secretion, including age, gender,
      body composition, regional distribution of fat and in particular abdominal
      visceral fat, sleep, nutrition, exercise and serum concentrations of gonadal
      steroids, insulin and IGF-I. Acute aerobic exercise is a powerful stimulus to GH
      release. Available studies suggest that intensity and duration of acute exercise,
      fitness, and training state may all influence, in part, the GH response to
      exercise. Intensity of exercise plays a key role in GH response to exercise. In
      the present paper we will discuss the GH response during acute aerobic exercise
      with a focus on exercise intensity and GH release. We will also provide an
      overview of the neuroendocrine control of exercise-induced GH release. Finally,
      information related to the effects of aging and gender on the GH response to
      exercise will be provided.

PMID- 14964437
TI  - Metabolic response to exercise.
AB  - At the beginning, the survival of humans was strictly related to their physical
      capacity. There was the need to resist predators and to provide food and water
      for life. Achieving these goals required a prompt and efficient energy system
      capable of sustaining either high intensity or maintaining prolonged physical
      activity. Energy for skeletal muscle contraction is supplied by anaerobic and
      aerobic metabolic pathways. The former can allow short bursts of intense physical
      activity (60-90 sec) and utilizes as energetic source the phosphocreatine shuttle
      and anaerobic glycolysis. The aerobic system is the most efficient ATP source for
      skeletal muscle. The oxidative phosporylation of carbohydrates, fats and, to a
      minor extent, proteins, can sustain physical activity for many hours.
      Carbohydrates are the most efficient fuel for working muscle and their
      contribution to total fuel oxidation is positively related to the intensity of
      exercise. The first metabolic pathways of carbohydrate metabolism to be involved
      are skeletal muscle glycogenolysis and glycolysis. Later circulating glucose,
      formed through activated gluconeogenesis, becomes an important energetic source.
      Among glucose metabolites, lactate plays a primary role as either direct or
      indirect (gluconeogenesis) energy source for contracting skeletal muscle. Fat
      oxidation plays a primary role during either low-moderate intensity exercise or
      protracted physical activity (over 90-120 min). Severe muscle glycogen depletion
      results in increased rates of muscle proteolysis and branched chain amino acid
      oxidation. Endurance training ameliorates physical performance by improving
      cardiopulmonary efficiency and optimizing skeletal muscle supply and oxidation of
      substrates.

PMID- 14964438
TI  - Growth, body composition and hormonal axes in children and adolescents.
AB  - Growth and physical maturation are dynamic processes that encompass a broad range
      of cellular and somatic changes. Most investigators who study growth have focused
      on linear growth (change in height over time), but alterations in the relative
      body proportions, body composition, and the regional distribution of body fat
      (upper body vs lower body, axial vs appendicular, and sc vs deep visceral) are
      essential elements for growth and sexual maturation. In fact, cardiovascular risk
      assessment in the adult relies heavily on the regional distribution of body fat.
      The antecedents for the adult pattern of fat are clearly present in the
      adolescent, if not the younger child. Standards for each of these parameters have
      been developed for multiple ethnic and racial populations and aid materially in
      the identification of children with normal growth and physical development,
      variations within the broad normal (physiological) range, and those with clearly
      pathological growth patterns.

PMID- 14964439
TI  - Ageing, growth hormone and physical performance.
AB  - Human ageing is associated to a declining activity of the GH/IGF-I axis and to
      several changes in body composition, function and metabolism which show strict
      similarities with those of younger adults with pathological GH deficiency. The
      age-related changes of the GH/IGF-I axis activity are mainly dependent on age
      related variations in the hypothalamic control of somatotroph function, which is
      also affected by changes in peripheral hormones and metabolic input. The term
      "somatopause" indicates the potential link between the age-related decline in GH
      and IGF-I levels and changes in body composition, structural functions and
      metabolism which characterise ageing. Physical exercise is an important
      environmental regulator of the GH/IGF-I axis activity. Increased physical fitness
      and regular training increase GH production in adults, while the GH response to
      aerobic or resistance exercise is reduced with age. In older subjects regular
      exercise has the potential to improve overall fitness and quality of life and is
      also associated to decreased morbidity and increased longevity. Similar effects
      are seen following GH therapy in adult deficiency. This assumption led to
      clinical trials focusing on rhGH and/or rhlGF-I as potential anabolic drug
      interventions in elderly subjects. To restore the activity of GH/IGF-I axis with
      anabolic, anti-ageing purposes, attention has been also paid to GH-releasing
      molecules such as GHRH, orally active synthetic GH-secretagogues (GHS) and, more
      recently, to the endogenous natural GHS, ghrelin, which exerts several important
      biological actions, including the regulation of metabolic balance and orexigenic
      effects. At present, however, there is no definite evidence that "frail" elderly
      subjects really benefit from restoring GH and IGF-I levels within the young adult
      range by treatment with rhGH, rhlGF-I, GHRH or GHS. In this article the
      alteration of the GH/IGF-I axis activity during ageing is revised taking into
      account the role of physical activity as a regulator of the axis function and
      considering the effects of the restoration of GH and IGF-I circulating levels on
      body composition and physical performance.

PMID- 14964440
TI  - Exercise-induced endocrine pathologies.
AB  - There has been a substantial increase in women practicing sports over the past 30
      yr. While exercise provides many health benefits, there appears to be a unique
      set of risks associated with intense exercise for the female athlete. The female
      athlete triad encompasses these risks, including amenorrhea, osteoporosis and
      eating disorders. The incidence of menstrual irregularities including primary and
      secondary amenorrhea and shortened luteal phases is much higher among women
      partaking in athletics, specifically in sports requiring low body weight for
      performance and aesthetics. The hormone pattern seen in these amenorrheic
      athletes includes a decrease in GnRH pulses from the hypothalamus, which results
      in decreased pulsatile secretion of LH and FSH and shuts down stimulation of the
      ovary. The recently discovered hormone leptin may also play a large role as a
      significant mediator of reproductive function. The prevalence of eating disorders
      is high among female athletes who practice sports which emphasize leanness.
      Consequently, the cause of menstrual irregularities is not due to the exercise
      alone, but to chronic inadequate or restrictive caloric intake that does not
      compensate for the energy expenditure. The most dangerous risk associated with
      amenorrhea for the female athlete is the impact on the skeleton. Complications
      associated with amenorrhea include compromised bone density, failure to attain
      peak bone mass in adolescence and increased risk of stress fractures. The
      diagnosis of exercise-associated menstrual dysfunctions is one of exclusion. The
      most effective treatment is to decrease the intensity of the exercise and
      increase the nutritional intake. Hormone replacement has also been under
      investigation as a possible treatment.

PMID- 14964441
TI  - Mechanisms underlying the neuroendocrine response to physical exercise.
AB  - Exercise initiates a coordinated series of physiological responses, including
      hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system
      activation, that, in combination, lead to the appropriate selection and
      utilization of metabolic substrates. Physical activity acts as a powerful
      stimulus for the hypothalamic-pituitary axis, leading to the liberation of
      several neuroendocrine hormones. The nature of this stimulation varies according
      to the kind of exercise (intensity, duration, aerobic, strength) and subject
      characteristics (gender, previous training), as well as depending on the time of
      the day and meal ingestion. As a whole, the neuroendocrine responses to exercise
      represent an accurate regulator of fuels (glucose, free fatty acids) homeostasis
      in a special situation characterized by a drastic increase of the energy
      requirements at muscle level. In this article the current knowledge about this
      topic is reviewed.

PMID- 14964442
TI  - Effects of androgen replacement on metabolism and physical performances in male
      hypogonadism.
AB  - Hypogonadism in men is associated with decreased physical performance. This
      phenomenon depends on significantly measurable adverse traits in body
      composition, namely increased body fat content and reduced muscle mass. Physical
      abilities in hypogonadal men are further hampered by lower oxygen supply due to
      decreased hemoglobin concentrations and by poor glucose utilization. In addition,
      dysthymia and lack of necessary aggressiveness contribute to further
      deterioration of physical features. T substitution can improve lipid and insulin
      metabolism, resuiting in changes of body composition, such as decreasing fat
      depots. Growth of muscle fibers can also be observed. Stabilization of the
      musculo-skeletal system by increased bone density will further contribute to
      increased physical fitness, reflected by increased strength and endurance.
      Treatment outcome is strongly influenced by age and training. The issues reviewed
      strongly support T treatment of hypogonadal men accompanied by regular
      monitoring.

PMID- 14964443
TI  - Body composition and muscle performance during menopause and hormone replacement
      therapy.
AB  - Menopausal transition is characterized by ovarian failure and its consequent
      decrease in female sex steroid production. Earlier studies suggest that an
      increase and redistribution of body fat during menopause predispose women to
      cardiovascular disease and metabolic syndrome. In addition, peri- and post
      menopausal women seem to have less lean body mass (LBM) compared with pre
      menopausal women. Accordingly, a changing ovarian hormonal status may accelerate
      the loss of muscle mass and result in decreased muscle performance and functional
      capacity. Hormone replacement therapy (HRT) has been used to treat menopausal
      symptoms and as a primary prevention therapy in chronic conditions. Inconsistent
      findings have, however, been published on the effects of HRT on body composition
      in post-menopausal women. Some studies clearly suggest that HRT counteracts
      menopause-related changes in body composition whereas others fail to show any
      difference between post-menopausal HRT users and abstainers. Although cross
      sectional studies show conflicting results concerning the association between HRT
      and muscle performance, experimental trials suggest that deterioration in muscle
      force during menopause can be prevented by HRT. In the future, longitudinal data
      need to be collected to confirm changes in body composition and muscle
      performance during menopausal transition irrespective of age. Although HRT seems
      to have beneficial effects on body composition and muscle performance in healthy
      post-menopausal women, there is considerable variation in the effects of HRT
      between different studies. The underlying mechanism of HRT action on muscle
      performance is still unclear.

PMID- 14964444
TI  - Effects of estrogen replacement on metabolic factors that influence physical
      performance in female hypogonadism.
AB  - There is a lack of knowledge regarding the effects of estrogens on physical
      performance. This is related, in part, to the challenge of isolating the effects
      of estrogens from those of progestins, because levels of both hormones fluctuate
      across the menstrual cycle, both decline during the menopausal transition, and
      the administration oh hormones to hypogonadal women typically involves a
      combination of estrogens and progestins. Some research findings suggest that
      fluctuations in estrogen levels acutely influence factors that may affect
      physical performance, such as substrate utilization or maximal aerobic power, but
      solid evidence is lacking. The simple observation that hypogonadism is not
      uncommon among elite athletes in some sports suggests that estrogen deficiency
      does not have a major negative impact on athletic performance. However, chronic
      hypogonadism may ultimately lead to impaired performance by menas that are not
      necessarily obvious. For example, chronic estrogen deficiency has potent,
      deleterious effects on the skeleton that can increase risk for stress fracture
      and may limit the ability to sustain a high level of physical training. Estrogen
      deficiency also appears to promote fat accumulation and may accelerate the loss
      of fat-free mass, and both of these changes in body composition could impair
      physical performance. There is evidence that hormone replacement attenuates the
      negative effects of hypogonadism on body composition and bone density, and that
      effects are mediated primarily by estrogens rather than progestins. Further
      research is necessary to broaden the understanding of the role of the estrogens
      in physical performance.

PMID- 14964445
TI  - Effects of GH replacement on metabolism and physical performance in GH deficient
      adults.
AB  - GH deficiency (GHD) in adults is associated with abnormalities in body
      composition, metabolic derangements, sub-optimal physical performance, high
      incidence of adverse cardiovascular risk factors and poor quality of life. GHD
      adults are insulin resistant and have reduced hepatic glycogen stores, reduced
      insulin stimulated glucose utilization and reduced glycogen synthesis in muscle.
      GH replacement results in either no change or slight reduction in insulin
      sensitivity. Hence, it is important to monitor for the development of glucose
      intolerance in patients on long-term GH replacement. GHD is associated with a
      lipid profile known to predispose to premature atherosclerosis and cardiovascular
      disease, i.e. increased total and LDL cholesterol, decreased HDL cholesterol,
      increased small dense LDL particles and increased triglycerides. LDL-cholesterol
      abnormalities appear to improve with GH replacement even if maintained within
      physiological dose range; the greatest improvement occurs in those subjects with
      higher baseline total and LDL cholesterol values and in female patients with
      adult onset GHD compared with male patients with childhood onset GHD. In
      contrast, hypertriglyceridaemia is not corrected by GH replacement. The majority
      of the reports suggest GH replacement increases Lipoprotein-a levels. Long-term
      observation will be required to determine whether GH replacement reduces
      cardiovascular morbidity and mortality in GHD adults. The reduced muscle mass and
      strength associated with GHD has been shown to improve after GH replacement. GH
      treatment also improves maximal and sub-maximal exercise performance in GHD
      adults. The effects on protein metabolism, energy expenditure and thyroid
      metabolism in GHD adults are also critical.

PMID- 14964446
TI  - Indirect evidence of hormone abuse. Proof of doping?
AB  - Besides anabolic steroids, the most common performance-enhancing hormones are
      erythropoietin (EPO), insulin, GH, and gonadotropins, mostly indistinguishable
      from endogenous hormones and with very short half-life. This makes virtually
      impossible to demonstrate their use by measuring their concentration in the blood
      or urine. A possible approach to the problem may lie in in-direct demonstration
      through detection of the biological effects of these substances. The finding of
      an increased hematocrit level is suspicious but not clearly demonstrative of EPO
      abuse. Very high levels of circulating EPO could be associated with a strong
      suspicion of doping, when associated to other abnormal parameters, such as Ht,
      sTFRr, EPO, RDW. The presence of antibodies against the polysaccharide fraction
      of lateral chains of EPO has been observed only in patients treated with rhEPO.
      Owing to the pulsatile pattern of GH, particularly during physical exercise,
      pathologically high values may be found in normal subjects. Therefore, as in the
      case of EPO, evidence of GH abuse can be gathered only indirectly by detecting
      the biological effects of its administration. In training subjects GH treatment
      increased GH, IGF-I, IGFBP-3 and ALS, and decreased IGBP-2. After cessation of
      treatment IGF-I, IGFBP-3 and ALS approached basal values between 49 and 96 h.
      Also the bone parameters PICP ICIP, PIUP and osteocalcin increased significantly.
      Four days after cessation of treatment, levels of PIIIP and ICTP were still
      abnormally elevated. In conclusion, increases in IGF-I, IGFBP-3, ALS, PIIIP and
      ICTP are all indicative of recent GH abuse or of acromegaly.

PMID- 14964447
TI  - Problems with GH doping in sports.
AB  - Human hGH is listed as a prohibited class E substance by the International
      Olympic Committee (IOC), and its use is considered as doping. However, until
      today the likelihood of being punished for using recombinant hGH is very limited:
      once injected, it is believed to be undetectable by laboratories. No official
      test is implemented in the doping control procedures, and the only situation when
      athletes were found guilty of doping with hGH arose from actions of customs
      officers or policemen arresting athletes carrying ampoules with them. The primary
      reason for the lack of an accepted test method is the amino acid sequence
      identity between the main fraction of pituitary derived hGH and recombinant hGH,
      which makes it difficult to discriminate between endogenous and exogenous hGH. In
      addition, hGH is known to have a very short half-life time in circulation of
      around 15 min. Recent efforts of endocrine researchers led to the identification
      of two main strategies promising to be useful for the detection of recombinant
      hGH application, which are reviewed in this article: on the one hand, changes in
      GH-dependent parameters after administration of recombinant GH have been shown to
      be possible indicators of GH abuse, because the increase in various parameters
      following recombinant hGH administration exceeds the variability commonly
      observed in normal, healthy subjects. More directly, another approach focuses on
      changes in the hGH isoform pattern in serum occurring after injection of
      recombinant hGH. Because of the negative feedback on pituitary hGH secretion, the
      relative abundance of isoforms other than 22 kD are greatly reduced after
      administration of recombinant hGH, which only consists of the 22 kD hGH isoform.

PMID- 14964448
TI  - Hormone use and abuse: what is the difference between hormones as fountain of
      youth and doping in sports?
AB  - GH can induce changes in body composition that are considered to be advantageous
      to aging subjects especially. However, there are no results indicating that the
      use of GH during aging should be advocated, because of the lack of any proven
      efficacy for whatever parameter. Also, data indicate that calorie restriction can
      extend life spans by altering the rate of decline in reserve capacity as well as
      by reducing the cumulative exposure to GH. Moreover, animal data suggest that
      lower GH actions are positively correlated with longevity. The abuse of GH by
      sportsmen is based on the belief that it has potent anabolic effects, while it is
      difficult to detect the abuse. Again, this supposed efficacy cannot be supported
      by any scientific data.

PMID- 14964449
TI  - Diabetes and exercise.
AB  - Physical activity has acute and chronic effects on glucose, lipid and protein
      metabolism. Long-term effects of regular exercise are particularly advantageous
      for Type 2 diabetic patients. Regular aerobic exercise reduces visceral fat mass
      and body weight without decreasing lean body mass, ameliorates insulin
      sensitivity, glucose and BP control, lipid profile and reduces the cardiovascular
      risk. For these reasons, regular aerobic physical activity must be considered as
      an essential component of the cure of Type 2 diabetes mellitus. In this regard,
      individual behavioral strategies have been documented to be effective in
      motivating sedentary Type 2 diabetic subjects to the adoption and the maintenance
      of regular physical activity. In Type 1 diabetic subjects, the lack of the
      physiological inhibition of insulin secretion during exercise results in a
      potential risk of hypoglycemia. On the other hand, exercise-induced activation of
      counter-regulatory hormones might trigger an acute metabolic derangement in
      severe insulin-deficient subjects. Thus, diabetic patients, before starting
      exercise sessions, must be carefully educated about the consequences of physical
      activity on their blood glucose and the appropriate modifications of diet and
      insulin therapy.

PMID- 14964450
TI  - Maternal nutrition, fetal weight, body composition and disease in later life.
AB  - Nutritional and hormonal milieu in utero affect fetal growth. Both parties
      involved have an independent chance, for the occurrence of a developmental error
      at any stage of their constant developing system. Studies suggest that pregnancy
      outcome is associated with fetal demand for nutrients and the materno-placental
      capacity to meet that demand. Failure of the materno-placental supply line to
      satisfy fetal nutrient requirements results in a range of fetal adaptations and
      developmental changes, and may lead to permanent alterations in the body's
      structure and metabolism, and thereby to cardiovascular and metabolic disease in
      adult life. Changes in the in-utero homeostasis may lead to programming of
      endocrine and metabolic systems so that feedback systems and reactions are
      permanently changed. At the present stage, short- and long-term hazards of intra
      uterine growth retardation (IUGR) have been identified, but preventive strategies
      are still lacking. It is unlikely that a single factor will reduce a multi-causal
      outcome like IUGR. Appropriate population-specific interventions should be a
      priority.

PMID- 14964451
TI  - Prevalence of proteinuria and the development of chronic kidney disease in HIV
      infected patients.
AB  - AIMS: HIV-related renal diseases are increasingly prevalent and are associated
      with proteinuria and rapid progression to end-stage renal failure. Early
      treatment with highly active antiretroviral therapy (HAART) and ACE inhibition
      may prevent the development of chronic kidney disease (CKD), but studies
      evaluating the epidemiology of proteinuria and early CKD in HIV-infected patients
      are lacking. METHODS: All consecutive patients at Wishard Memorial Hospital
      (Indiana University) whose initial HIV documentation occurred from 1990 to 1998,
      were retrospectively studied using a computerized medical record system. Clinical
      data were abstracted from time of first HIV documentation through 12/31/2000. The
      proportions of patients who developed CKD (doubling of serum creatinine from an
      initial level < or = 1.5 mg/dl) and who had proteinuria (> or = 1+ protein on the
      first urine dipstick after HIV documentation) were calculated. Case mix and
      laboratory variables at the time of HIV documentation were compared between those
      who did and did not develop CKD and between those who had and did not have
      initial proteinuria. RESULTS: Of 487 subjects with initially normal renal
      function, 10 (2% (95% CI, 1-4%)) developed CKD. In univariable analysis, black
      race, a diagnosis of diabetes or hypertension and proteinuria were all
      significantly associated with the development of CKD; 89 (29% (95% CI, 24-35%))
      of 289 evaluable subjects had > or = 1+ proteinuria on urine analysis.
      Multivariable regression revealed only older age (OR 1.08 per year increase; 95%
      CI, 1.03-1.14) to be associated with proteinuria. CONCLUSIONS: A small, but
      potentially clinically meaningful proportion of HIV-infected patients develop
      CKD, and there appears to be a high prevalence of proteinuria on the first urine
      analysis obtained after HIV documentation.

PMID- 14964452
TI  - Glomerular expression of biglycan and decorin and urinary levels of decorin in
      primary glomerular disease.
AB  - AIMS: Recent studies have suggested that small leucine-rich proteoglycans (SLRP)
      of the extracellular matrix play a major role in modulating the activity of
      growth factors and in regulating the deposition of collagens. In this study, the
      expression of the SLRPs biglycan and decorin in the glomeruli of patients with
      primary glomerular disease (minimal change disease, IgA nephropathy, and
      membranous nephropathy) and urine immunoreactive levels examined. METHODS: Renal
      biopsy specimens were obtained from patients with minimal change disease, IgA
      nephropathy and membranous nephropathy. Immunohistochemical staining was
      performed on fresh-frozen samples using anti-biglycan and anti-decorin
      antibodies. Examination of urine proteoglycan excretion from a total of 26
      patients and 8 normal volunteers was performed by indirect ELISA. RESULTS: In
      normal kidney samples, biglycan and decorin expression was found predominantly in
      the intrarenal arteries and tubulointerstitium, with only minimal expression in
      the glomeruli. Glomerular expression of these proteoglycans in glomerular disease
      was unchanged in all of the 4 patients examined with minimal change disease. In
      the case of IgA nephropathy or membranous nephropathy, some of the patients
      showed minimally increased immunostaining of either biglycan or decorin, but
      there were no signs of simultaneous upregulation of both proteoglycans. To
      further examine the changes in proteoglycan expression, ELISA was performed on
      urine samples. Urine biglycan levels were below detection levels, but high values
      of urine decorin immunoreactivity were found in the patients with glomerular
      disease. A significant negative correlation was found between urine decorin and
      creatinine clearance. CONCLUSION: These results suggest that distinct changes in
      the expression of the SLRPs biglycan and decorin may be seen in patients with
      primary glomerular disease. Moreover, the negative relationship between urine
      decorin levels and renal function supports the hypothesis that decorin may be
      involved in the pathophysiology of renal dysfunction in humans.

PMID- 14964453
TI  - The remission of nephrotic syndrome with cyclosporin treatment does not attenuate
      the progression of idiopathic membranous nephropathy.
AB  - BACKGROUND: Idiopathic membranous nephropathy (IMN), a common cause of nephrotic
      syndrome in adults, is usually treated by combination of corticosteroids with
      cytotoxic drugs. In cases resistant to this regimen, the use of cyclosporin A
      (CsA) is followed by frequent remissions of the nephrotic syndrome. AIM: The
      purpose of this study was to estimate the effectiveness of prednisolone and small
      doses of CsA as first-line treatment of nephrotic patients with IMN, in relation
      to the progression of the disease, based on functional and histological changes.
      PATIENTS AND METHODS: Sixteen patients, with nephrotic syndrome due to IMN and
      well-preserved renal function, were treated with prednisolone (starting dose: 0.5
      mg/kg bw/day) and CsA (starting dose: 3 mg/kg bw/day) for 24 months. A repeat
      renal biopsy was performed after 18 months of treatment in 10 patients with
      remission of nephrotic syndrome, to estimate the activity of the disease and to
      identify any features of CsA toxicity. RESULTS: Remission of the nephrotic
      syndrome was observed in 14 out of 16 patients after 5 +/- 2 months of treatment.
      Complete remission was observed in 8 and partial remission in 6 patients (urinary
      protein was reduced from 6.9 +/- 3.4-0.2 +/- 0.06 g/24 h and 1.2 +/- 1.0 g/24 h,
      respectively, p < 0.01). The renal function was well preserved in 13 out of 16
      patients over a 24-month period of treatment. Deterioration of renal function was
      observed in 3 patients (creatinine clearance reduced from 86 +/- 21-37 +/- 17
      ml/min, p < 0.05) who had either persistent nephrotic syndrome or frequent
      relapses. Relapses of the nephrotic syndrome were observed in 5 of 14 patients.
      Repeat renal biopsies showed that glomerular sclerosis, tubulointerstitial
      injury, vascular hyalinosis and stage of the disease were deteriorated in most
      patients. Isometric vacuolization of tubular epithelial cells was observed in 2
      of 10 patients. CONCLUSION: IMN nephrotic patients treated with prednisolone and
      low doses of cyclosporin A showed a high remission rate of nephrotic syndrome.
      However, progression of chronic histological lesions was found in repeat renal
      biopsies. This suggests that cyclosporin can frequently induce remission of
      nephrotic syndrome in IMN patients, but even low doses of the drug are not free
      of potential renal toxicity.

PMID- 14964454
TI  - Mycophenolate mofetil in children with multidrug-resistant nephrotic syndrome.
AB  - AIM: The aim of the present study is to report our clinical experiences with MMF
      in problematic children with chronic glomerulonephritis resistant to
      corticosteroids and/or other immunosuppressive drugs. PATIENTS AND METHODS: Ten
      patients with chronic glomerulonephritis resistant to treatment with
      corticosteroids and other immunosuppressive drugs were treated with mycophenolate
      mofetil (MMF). Causes of chronic glomerulonephritis were mesangial proliferative
      glomerulonephritis (4), membranoproliferative glomerulonephritis (3), chronic
      sclerosing glomerulonephritis (1), focal segmental glomerulosclerosis (1),
      diffuse endo- and extracapillary proliferative glomerulonephritis (1). MMF 15
      mg/kg was used in combination with low-dose corticosteroids and angiotensin
      converting enzyme inhibitors. RESULTS: During 24 weeks of MMF therapy, no
      significant changes were detected in mean serum creatinine, albumin and
      proteinuria. Severe leukopenia was seen in 1 patient. Additional adverse effects,
      including nausea and diarrhea, were observed in another patient when the dosage
      was increased to 20 mg/kg per day. During MMF treatment proteinuria decreased
      slightly without remission in 6 of 10 patients. CONCLUSION: Further data and
      clinical trials are needed to evaluate the possible role of MMF in the treatment
      of chronic glomerulonephritis of similar etiologies in pediatric patients.

PMID- 14964455
TI  - Differential expression of beta-chemokines MCP-1 and RANTES and their receptors
      CCR1, CCR2, CCR5 in acute rejection and chronic allograft nephropathy of human
      renal allografts.
AB  - BACKGROUND: The beta-chemokines MCP-1 (CCL2) and RANTES (CCL5) have been shown to
      play important roles in acute renal transplant rejection (AR) and chronic
      allograft nephropathy (CAN). The potential relationship of expression of these
      chemokines, their chemokine receptors CCR1, CCR2, CCR5, and the cell populations
      of inflammatory infiltrate, histological and clinical diagnoses were investigated
      in biopsies at the time of AR and compared with biopsies of CAN. METHODS: In 24
      renal transplant biopsies with AR (n = 15) and CAN (n = 9), the expression of MCP
      1 and RANTES, their receptors CCR1, CCR2, and CCR5 and the infiltration with
      monocytes/macrophages and T cells were studied. RESULTS: As previously described,
      chemokine and chemokine receptor expression was found mainly in mononuclear cells
      infiltrating the interstitium and glomeruli. In the tubulointerstitial area and
      glomeruli the expression of MCP-1, RANTES, and their receptors correlated with an
      infiltration by monocytes/macrophages. Biopsies with CAN revealed a lower
      expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in tubulointerstitial cells, and
      a significantly lower infiltration with MRP14-positive monocytes/macrophages than
      biopsies with AR. In AR, MCP-1 and CCR1 showed a lower expression compared to
      RANTES, CCR2, and CCR5. CONCLUSIONS: The positive correlation between chemokines
      and chemokine receptors and infiltrating leukocytes during acute rejection, the
      lower but detectable expression of MCP-1, RANTES, CCR1, CCR2 and CCR5 in CAN, and
      the differences in the quantity of expression between the different chemokines
      and chemokine receptors point to a complex regulation of chemokine expression in
      renal allografts. Since chemokines are not only involved in inflammation but also
      in tissue regeneration, this could have impact on the development of CAN.

PMID- 14964456
TI  - Single and serial measurements of cardiac troponin I in asymptomatic patients on
      chronic hemodialysis.
AB  - AIMS: Coronary artery disease is the major cause of death in patients with end
      stage renal failure on dialysis. This study aimed to assess the predictive value
      of a single cardiac troponin I (cTnI), and also the kinetics of serial values.
      METHODS: Since cTnI is a potential biomarker of cardiac outcome, the present
      study examined single cTnI measurements (n = 88 patients) and its predictive
      value for future cardiac events, and a kinetic substudy of serial weekly cTnI
      measured for 8 weeks (n = 57) in a group of patients on hemodialysis. RESULTS:
      Single cTnI measurements: 9 patients (10.2%) had a detectable cTnI at baseline
      and 79 patients (89.8%) had a negative baseline cTnI. There were no significant
      differences in age, sex, history of ischemic heart disease, diabetes, smoking or
      dyslipidemia between patients with detectable and negative cTnI. At the end of 9
      months, the rate of combined primary endpoints, which included myocardial
      infarction, cardiac death and cardiac revascularization, was significantly higher
      in the patients with a detectable baseline cTnI (55.6%), compared to patients
      with a negative cTnI (6.3%) (p = 0.0007). Serial weekly cTnI measurements:
      significant fluctuations in cTnI were noted over time; 27% of patients with an
      undetectable cTnI measured at baseline had subsequent detectable levels in the
      serial follow-up. CONCLUSION: A single detectable cTnI in asymptomatic patients
      on hemodialysis defines patients at high risk of future cardiac events. However,
      the incidence of detectable cTnI levels is markedly increased when serial weekly
      measurements are performed. The clinical significance of detectable serial
      measurements of cTnI is the focus of ongoing studies.

PMID- 14964457
TI  - Efficacy of reteplase in poorly functioning hemodialysis catheters.
AB  - AIM: This is a retrospective study of reteplase efficacy for restoration of flow
      in occluded and poorly functioning hemodialysis catheters. PATIENTS AND METHODS:
      From May 1, 2001 to December 31, 2001, all hemodialysis patients seen at our
      university dialysis center with occluded or poorly functioning (< 200 ml/min
      blood flow) catheters treated with reteplase were included in the study. All
      catheters had been in place for more than 48 hours. Reteplase 0.4 U was instilled
      into each port; dwell time was 30 minutes. If aspiration had not been possible,
      reteplase had remained in the catheter for an additional 30 minutes. If flow was
      established (> 200 ml/min), the catheter was used for dialysis. If flow was not
      adequately established after 1 hour, the patient was referred for catheter
      exchange. RESULTS: Reteplase (0.4 U) was used in 50 instances to restore or
      improve blood flow rates in a total of 23 catheters in 19 patients. Reteplase was
      effective in establishing adequate blood flow rates during the current and next
      dialysis session in 44/50 (88%) cases; 6 cases required 1-hour dwell time. Six
      cases (in 5 patients) required catheter exchange; in these, an anatomic or
      pathologic complication was responsible for catheter malfunction. No adverse
      events were related to reteplase instillation during the study. CONCLUSION: Data
      suggest that reteplase is safe and effective in restoring flow to malfunctioning
      hemodialysis catheters. Results are comparable to those achieved with alteplase.

PMID- 14964458
TI  - Hyponatremia in peritoneal dialysis patients.
AB  - BACKGROUND: Low serum sodium is uncommon in peritoneal dialysis (PD), which is
      surprising in view of the important role of normal kidney function to regulate
      water and sodium balance. METHODS: We report 2 cases of persistent hyponatremia
      with balance studies in Case 1. We performed measurements of dialysate sodium and
      volume output over 24 hours in a group of chronic PD patients. RESULTS: The low
      serum sodium concentration did not vary too much with overall fluid removal via
      dialysis in patient 1, mainly because large quantities of sodium were removed in
      the dialysate. In the 24-hour studies, a significant relationship was found
      between net daily PD sodium removal and net daily dialysate volume removed (r =
      0.65). There was no relationship between net daily PD sodium removal and serum
      sodium concentration. There was a linear direct correlation between serum and
      dialysate sodium concentration (r = 0.8) as shown by others previously.
      CONCLUSIONS: These results suggest that the main determinant of PD sodium loss is
      net dialysate ultrafiltration volume. Water loss via dialysis is necessarily
      associated with sodium loss. In order to maintain a normal serum sodium
      concentration salt intake must be proportional to the water loss induced by
      dialysis. The stimuli that allow dialysis patients to maintain this delicate
      balance between water and salt intake are of considerable interest but remain
      undetermined.

PMID- 14964459
TI  - Pregnancy in membranous glomerulonephritis--course, treatment and outcome.
AB  - BACKGROUND: The effect and outcome of pregnancy in women with preexisting
      glomerulonephritis is a controversial issue. CASE: We report the clinical course
      and treatment of a 23-year-old pregnant woman with biopsy-proven membranous
      glomerulonephritis. When she conceived, the patient had been in stable remission
      for 1 year. In the 14th week of pregnancy, the patient developed uncontrolled
      hypertension and nephrotic syndrome. Daily 1 g methylprednisolone intravenous
      pulses were administered for 3 days, followed by a 4-week course of oral
      prednisone, 50 mg/day. Clinical improvement and normalization of arterial blood
      pressure were achieved. Oral prednisone 60 mg was administered on alternate days
      for another 4 weeks following 3 days of pulse therapy. At the end of treatment
      (26th gestational week), we observed a decrease of proteinuria (from 10.6-4.8
      g/24 h) and rise in serum albumin (from 2.1-2.9 g/100 ml). At this time, blood
      pressure was 130/85. In the 34th week, a normal healthy male newborn was
      delivered by cesarean section. One year later she felt well, her blood pressure
      was 140/90, serum albumin was 3.4 g/100 ml, urine protein was 1.65 g/24 h and
      renal function was normal. The patient's child was healthy and well developed.
      CONCLUSION: Judicious use of a specific therapy to the underlying renal disease
      during pregnancy, together with a continuous supervision, can improve outcomes of
      these particular high-risk conditions.

PMID- 14964460
TI  - Pamidronate-induced nephrotoxic tubular necrosis--a case report.
AB  - Few cases of pamidronate (bisphosphonate class of drugs) nephrotoxicity in humans
      have been previously reported in the literature. In 7 patients, the pamidronate
      related nephrotoxicity was attributed to focal collapsing glomerulosclerosis
      [Markowitz et al. 2001], and in 1 patient was related to tubulo-interstitial
      inflammatory nephritis [Van Doom et al. 2001]. We report herein on a 65-year-old
      Caucasian female patient who presented with acute chronic renal failure due to
      pamidronate-induced toxic proximal tubular necrosis without immunologic or
      inflammatory tubulo-interstitial involvement. The acute pattern of renal failure
      resolved following cessation of pamidronate administration in this patient for
      osteoporosis; the patient also had a monoclonal gammopathy of unspecific origin
      (MGUS).

PMID- 14964461
TI  - A case of secondary hyperparathyroidism whose high turnover bone improved after
      the direct injection of acetic acid into the parathyroid glands.
AB  - A 48-year-old male was admitted to our hospital because of increasing knee pain
      and thigh muscle weakness. He had been undergoing hemodialysis for 15 years. His
      serum intact PTH value was 1,600 pg/ml with elevated ALP (387 IU/l) and
      osteocalcin (400 ng/ml). Ultrasound (US) examination disclosed 2 enlarged
      parathyroid glands. Because of poor cardiac function, an US-guided acetic acid
      injection into the enlarged parathyroids (percutaneous acetic acid injection
      therapy; PAIT) was performed. Soon after the PAIT, his arthralgia disappeared.
      Serum PTH fell to 220 pg/ml with the regression of bone marker 1 year following
      the PAIT. The size of his parathyroid glands dramatically regressed and 1 of the
      enlarged glands finally disappeared. Repeated bone biopsies following double
      tetracycline labeling showed a significant improvement from osteitis fibrosa to
      the mild lesion. This is the first known case report of severe secondary
      hyperparathyroidism whose PTH and high turnover bone was successfully managed by
      the direct injection of acetic acid into the parathyroid glands. As long as we
      pay attention to avoiding recurrent nerve palsy induced by acetic acid, US-guided
      PAIT may be an alternative to percutaneous ethanol injection therapy (PEIT) or
      surgical parathyroidectomy (PTx).

PMID- 14964462
TI  - Mechanical hemolysis in a hemodialysis patient with carotid-jugular arteriovenous
      fistula.
AB  - Renal anemia is mainly caused by inadequate synthesis of erythropoietin from
      diseased kidneys. At the present time, recombinant human erythropoietin (rHuEPO)
      is used to correct anemia successfully in most patients with end-stage renal
      diseases. Nevertheless, poor response to rHuEPO still exists in some hemodialysis
      patients and its mechanism in some cases remains obscure. Herein, we describe a
      rare case of rHuEPO hyporesponsiveness due to mechanical hemolysis induced by a
      traumatic carotid-jugular arteriovenous fistula (AVF) in the presence of
      subclinical aluminum intoxication. Following surgical resection of the traumatic
      AVF and 8 months of desferrioxamine treatment, the responsiveness to rHuEPO was
      restored and the rHuEPO dose requirements reduced.

PMID- 14964463
TI  - Acute renal failure secondary to hemoglobinuria in a patient with a left
      ventricular assist device.

PMID- 14964464
TI  - Recurrence of type III membranoproliferative glomerulonephritis after renal
      transplantation.

PMID- 14964465
TI  - An unusual case of a vesical stone presenting gross hematuria in a boy.

PMID- 14964466
TI  - Three cases of the gastrosplenic and the hepatomesenteric trunks.
AB  - Three common branches of the celiac trunk are the left gastric artery, the
      splenic artery and the common hepatic artery. The variation of the three branches
      of the celiac trunk has an importance for the arterial supply to the digestive
      organs of the upper abdomen. In this study, we present three cases of the
      gastrosplenic and the hepatomesenteric trunks in Japanese cadavers. Especially,
      in Case 1, the left inferior phrenic artery arose from the gastrosplenic trunk
      and the left hepatic artery arose from the left gastric artery. In Cases 2 and 3,
      the common hepatic artery penetrated the pancreatic parenchyma before reaching
      liver. In Case 3, the right hepatic artery arose from the hepatomesenteric trunk.

PMID- 14964467
TI  - Bilateral aberrant biceps brachii muscles with special reference to their common
      nerve trunks.
AB  - Aberrant biceps brachii muscles (BB); the right aberrant head, the left aberrant
      head, and the left aberrant bundle, were observed bilaterally in a 94-year-old
      Japanese female cadaver during a regional anatomy of the upper extremities. We
      examined the nerve supply as well as scrutinizing these aberrant BB. The branches
      to the right aberrant head and the right brachialis muscle arose as a common
      nerve trunk from the musculocutaneous nerve, and both branches entered each
      muscle from the ventral aspect. The branches to the superior portion of the left
      aberrant bundle and the short head of the BB arose as a common nerve trunk from
      the musculocutaneous nerve, and both branches entered each muscle from the dorsal
      aspect. The branches to the inferior portion of the left aberrant bundle and the
      left aberrant head arose separately from the musculocutaneous nerve, but they
      were found to be closely related after peeling off the epineurium. From these
      observations, we speculated that the right aberrant head could have
      differentiated from the brachialis muscle, the left aberrant head from the long
      head of the BB, and the left aberrant bundle aberrant head from the short and
      long head of the BB, based on the formation of the common nerve trunk and the
      close relation of the nerve fibers. Our suggested muscular differentiation agreed
      with the entering aspect (ventral/dorsal aspect) of the innervating nerve.

PMID- 14964468
TI  - Ultrastructure of the ovarian germ cells in the quail embryos, with special
      reference to the oocytes.
AB  - Developing germ cells from oogonia to oocyte stages in embryonic quail ovaries
      were observed ultrastructurally. In contrast with those of chicks, quail oocytes
      showed some conspicuous structures. Typical feature of the Balbiani body, which
      was constructed by eccentrical concentration of whole organelles, was observed
      through the oocyte stage, although loose aggregations of organelles were found
      even at the oogonial stage. Such striking feature of Balbiani body was not
      observed as yet in any animal species. Golgi apparatus, which occupied the center
      of a Balbiani body, was often found attaching with the nuclear membrane. This
      finding suggests that the Balbiani body play some role for the oocyte maturation.
      Upon the nuclear membrane of oocytes, a great number of electron dense structures
      were found. They were thought to be a kind of nuclear pore complexes. Such
      abundance of the nuclear pore complexes was another structural characteristic of
      quail oocytes. They increased in number according to the progress of embryonic
      development, although small numbers were also seen even at the oogonial stage.

PMID- 14964469
TI  - Immunohistochemical study of genesis of the mouse oral vestibule.
AB  - Immunohistochemical light microscopy by the enhanced polymer one-step staining
      (EPOS) method and immunohistochemical confocal laser scanning microscopy by the
      labelled streptavidin biotin (LsAB) method were performed on the developing
      vestibular lamina (VL) of fetal mice at stages from E11 to E14, and the
      immunohistochemical findings were compared with the findings in the developing
      dental lamina (DL) and tooth germ. pRb and PCNA were immunolocalized and found to
      be related to the temporal and spatial expression of cytokines and receptors in
      the primary epithelial band, VL, DL/enamel organ, and associated mesenchyme. The
      following results were obtained: 1) EGF, TGFalpha, EGFR, PCNA, FGF2, pRb, and
      FGFR1-4 were immunolocalized in the developing tissues. 2) Cytokine expression
      patterns indicated that the EGF family and FGF2 essentially induced VL generation
      and cell proliferation. 3) FGFR1 was diffusely localized in the primary
      epithelial band, but was strongly expressed in the E12-14 VL and DL/enamel organ.
      By contrast, EGFR internalization was observed in the differentiating E13 VL. 4)
      Expression of pRb was intensely localized in the stratum germinativum of the E13
      VL and corresponded to CK-10 expression in the keratinizing VL. The results of
      this study suggest a mechanism in which FGFR1 regulates pRb to induce
      proliferation of cells in the VL and DL/enamel organ, and, in particular, to
      incite keratocyte differentiation and subsequent exfoliation of keratinizing VL
      cells.

PMID- 14964470
TI  - The development of neurologic intensive care.

PMID- 14964471
TI  - The pathophysiology of brain edema and elevated intracranial pressure.

PMID- 14964472
TI  - Hypertonic saline for cerebral edema and elevated intracranial pressure.
AB  - The use of HS solutions has been shown to reduce ICP both in animal models and in
      human studies in a variety of underlying disorders, even in cases refractory to
      treatment with hyperventilation and mannitol. There are several possible
      mechanisms of action, and important complications such as central pontine
      myelinolysis and intracranial hemorrhage have not been reported in the human
      studies. Different types of HS solutions with different methods of infusion
      (bolus and continuous) have been used in the past, and so far there are not
      enough data to recommend one concentration over another. Many issues remain to be
      clarified, including the exact mechanism of action of HS, the best mode of
      administration and HS concentration to be given, and the relative efficacy of HS
      vis-a-vis available treatments, particularly mannitol.

PMID- 14964473
TI  - Every breath you take: hyperventilation and intracranial pressure.
AB  - Hyperventilation can rapidly lower ICP, but because it induces a consistent
      reduction in CBF and because the effects on ICP are transient, the only role that
      hyperventilation plays in the management of intracranial hypertension is in the
      management of acute elevations in ICP. In these circumstances, hyperventilation
      can be life-saving and can temporize until more definitive treatment of the
      intracranial hypertension can be undertaken.

PMID- 14964474
TI  - Multimodal monitoring in neurocritical care.

PMID- 14964475
TI  - Endovascular coiling: the end of conventional neurosurgery?

PMID- 14964476
TI  - Lessons from the medical and surgical ICU.

PMID- 14964477
TI  - Cerebrovascular disease: historical background, with an eye to the future.

PMID- 14964478
TI  - Pathophysiology of acute ischemic stroke.

PMID- 14964479
TI  - Intravenous thrombolysis for acute stroke.
AB  - Intravenous t-PA is effective if given to appropriate patients within 3 hours of
      stroke onset, and its effectiveness increases even within the first 3 hours when
      given as soon as possible. t-PA is reasonably safe if used in a carefully defined
      manner that ensures close attention to blood pressure, careful patient
      monitoring, no use of heparin and aspirin during first 24 hours, and appropriate
      patient selection. It is still unclear whether a lower dose of t-PA given with 3
      hours could be as effective as but safer than the currently approved intravenous
      dose of 0.9 mg/kg over 1 hour. The effectiveness and safety of intravenous t-PA
      when given beyond 3 hours after stroke onset has yet to be conclusively
      demonstrated. One attractive development is the potential use of imaging, such as
      diffusion/perfusion MRI to determine if salvageable brain remains and if t-PA
      should be given in patients who are beyond the 3-hour time window. The drawback
      to MRI is the additional time required before the start of recanalization
      therapy.

PMID- 14964480
TI  - Intra-arterial thrombolysis for acute stroke.

PMID- 14964481
TI  - Therapeutic hypothermia may enhance reperfusion in acute ischemic stroke.

PMID- 14964482
TI  - Stem cell transplantation for stroke.

PMID- 14964483
TI  - Carotid artery disease: from knife to stent.

PMID- 14964484
TI  - Carotid stenting in high-risk patients: design and rationale of the SAPPHIRE
      trial.

PMID- 14964485
TI  - Medical management of intracranial atherosclerosis: current state of the art.

PMID- 14964486
TI  - Intracranial stenting: which patients and when?

PMID- 14964487
TI  - Anticoagulation for stroke prevention: yes, no, maybe.

PMID- 14964488
TI  - Antiplatelet therapy for acute stroke: aspirin and beyond.

PMID- 14964489
TI  - Dentinal hypersensitivity: review of aetiology, differential diagnosis,
      prevalence, and mechanism.
AB  - Dentinal hypersensitivity is a painful response to a non-noxious stimulus applied
      to exposed dentine in the oral environment. Dentine exposure results from a
      combination of two or more aetiological factors that lead to loss of enamel
      and/or loss of cementum. The hydrodynamic theory is the most accepted theory that
      explains the excitement of pulpal nerve fibres by a stimulus applied to the
      exposed dentine. Dentinal hypersensitivity had been reported to affect middle age
      people most often with no gender differences and has been shown to be influenced
      by tooth location.

PMID- 14964490
TI  - Diabetes mellitus--a modifier of periodontal disease expression.
AB  - The understanding of causes and progression of periodontal disease has increased
      considerably in recent years making it all the more important to gain knowledge
      about diabetes and its interrelationship with periodontal disease so as to be
      able to assess their impact on one another more accurately. Strong evidence
      exists to support the fact that diabetic patients are at an increased risk for
      periodontitis. A number of underlying factors are known to contribute to enhanced
      periodontal destruction in diabetics. There has been intensive research to
      characterise the mechanisms responsible for the pathogenesis of both
      microvascular and macrovascular complications. It is also known that there is
      variability in the rate of development and severity of these complications with
      some diabetics experiencing none of them. Many of the host response traits that
      confer susceptibility to periodontitis in otherwise healthy individuals are
      exaggerated in diabetics. These diabetes associated susceptibility traits include
      neutrophil dysfunction, abnormal cross-linking and glycosylation of collagen,
      defective secretion of growth factors and subsequent impaired healing. However it
      is uncertain which of the hypothesised mechanisms or combinations of mechanisms
      is directly responsible for the pathogenesis of the complications or whether
      different mechanisms are operative in different tissues.

PMID- 14964491
TI  - Aspects of interleukin-8 gene expression by gingival and dermal fibroblasts
      stimulated with interleukin-1beta or tumour necrosis factor alpha.
AB  - Fibroblast-derived interleukin (IL)-8 is thought to have an important role in the
      orchestration of immuno-participant cells infiltrating the skin and gingiva in
      response to continuously recurring bacterial infection. Therefore, the IL-8 gene
      expression should be under tight regulatory control and it might be temporally
      and spatially limited in inflammatory tissue. The purpose of this study was to
      examine the aspect of the IL-8 gene expression by fibroblasts stimulated with pro
      inflammatory cytokines, IL-1beta and TNF-alpha. In situ hybridisation revealed
      that fibroblasts did not express IL-8 mRNA whereas keratinocytes and endothelial
      cells did in IL-1beta- or TNF-alpha-injected mice skin. However, cultured mouse
      dermal fibroblasts expressed not only IL-8 but also IL-1beta mRNA without
      stimulation by exogenous IL-1beta and TNF-alpha, and the expression was not
      enhanced by the exogenous cytokines. A similar result was obtained in late
      passage human gingival fibroblasts. These results suggest that fibroblasts remain
      insensitive to IL-1beta and TNF-alpha so as to induce the IL-8 gene expression in
      non-inflammatory mice skin. Mouse dermal and late-passage human gingival
      fibroblasts in vitro are likely to be altered in phenotype into IL-8-producing
      cells along with the production of IL-1beta. In skin inflammation and periodontal
      diseases, fibroblasts may express the IL-8 gene even without an exogenous
      cytokine, IL-1beta or TNF-alpha, during their proliferation similar to the
      situation in our culture system.

PMID- 14964492
TI  - Effect of the carbon dioxide laser on the clinical parameters and crevicular IL
      1beta when used as an adjunct to gingival flap surgery.
AB  - OBJECTIVE: This study evaluated the effect of a carbon dioxide (CO2) laser
      treatment on the clinical parameters and crevicular Interleukin-1 (IL-1beta)
      levels when used in combination with gingival flap surgery. METHODS: Twelve
      patients with moderate to advanced periodontitis were selected for this study.
      Three quadrants in each patient were randomly assigned to one of the following
      study groups: 1) flap surgery only as the (control); 2) flap surgery and laser
      treatment using an energy level of 0.8 W as (group 1); 3) flap surgery and laser
      treatment using an energy level of 0.5 W as (group 2). The gingival crevicular
      fluid (GCF) was collected at the baseline and biweekly for 6 weeks and the amount
      of IL-1beta concentration in the sulcular fluid was measured using an enzyme
      linked immunosorbent assay. The clinical parameters such as the probing pocket
      depth, the clinical attachment level, the gingival recession and the bleeding on
      probing were recorded at the baseline, 3, 6 months. RESULTS: Marked reductions of
      the bleeding on probing, the probing pocket depth, the clinical attachment level
      and a reduction in the crevicular IL-1beta concentration were found in all
      groups. However, the differences between the groups in terms of bleeding on
      probing and the probing pocket depth were not significant (p<0.05). The clinical
      attachment level and the crevicular IL-1beta level were significantly lower in
      group 1 (0.8 W) than in the control (p<0.05). CONCLUSION: The additional use of a
      carbon dioxide laser on the root surface during gingival flap surgery may enhance
      the clinical attachment and reduce the crevicular IL-1beta concentration.

PMID- 14964493
TI  - Military deployment health surveillance policy and its application to Special
      Operations Forces.
AB  - An evaluation research methodology was used to determine whether deployment
      health surveillance for Special Operations Forces conformed with Department of
      Defense policy directives for the specified target population. Data for this
      methodology were based on pre- and postdeployment health assessments as well as
      patient encounters recorded during deployments. The data represented 1,094
      individual and unique Special Operations Forces members deployed to 12 different
      countries from October 2000 through December 2001. Results from the study
      suggested that military deployment health surveillance policy goals for
      predeployment medical referrals, patient data capture, and documentation during
      the deployment and postdeployment medical referrals were being poorly met when
      Department of Defense and Joint Chiefs of Staff mandates were applied to Special
      Operations Forces in an unconventional operations environment. Preliminary
      evaluation indicates that deployment health surveillance implementation could be
      improved with the introduction of policy awareness education, training, and
      technology.

PMID- 14964494
TI  - Morphological and immunohistochemical changes on rat skin exposed to nitrogen
      mustard.
AB  - OBJECTIVE: The aim of this study was to understand the mechanism of nitrogen
      mustard on skin. METHODS: Nitrogen mustard was applied on ventral skin of 30
      rats. Sequential biopsies were taken during the postexposure period. Slides were
      stained with hematoxylin-eosin and keratin PAN and high molecular weight
      cytokeratin and keratin 5. RESULTS: The earliest findings are minimal
      polymorphonuclear leukocytes extravasation and edema. Heavy inflammation with
      formation of vesicles and bulla were present at 24 hours. At 6 hours, the upper
      epidermal cells showed weak staining with high molecular weight cytokeratin and
      keratin PAN. At 24 and 48 hours, only patchy areas of staining with high
      molecular weight cytokeratin and keratin 5 were present. CONCLUSION: One of the
      major mechanisms of injury by nitrogen mustard may be the disruption of
      cytoskeletal filament network.

PMID- 14964495
TI  - Pilot testing the Readiness Estimate and Deployability Index Revised for Air
      Force Nurses.
AB  - The Readiness Estimate and Deployability Index Revised for Air Force Nurses
      (READI-R-AFN) was derived from modifications of Reineck's Readiness Instrument.
      Reliability and validity of the READI-R-AFN was estimated on completed
      questionnaires of 181 active duty Air Force nurses. The READI-R-AFN was evaluated
      based on item analysis, internal consistency (alpha coefficient, >0.70),
      confirmatory factor analysis with structural equation modeling, and hypothesis
      testing. The findings were supported by Flannery's model of stress resistance.
      There was evidence of reliability and validity of the 83-item READI-R-AFN based
      on internal consistency (alpha, 0.80-0.96), structural equation modeling, and
      hypothesis testing. The original hypothesized six dimensions were retained.

PMID- 14964496
TI  - The implications of TRICARE on medical readiness.
AB  - The objective of this study was to compare two alternative sources of replacement
      personnel for a medical treatment facility experiencing personnel loss due to a
      deployment. The two replacement strategies included the reserve component option
      and the TRICARE internal resource-sharing option. A hypothetical scenario was
      used as a mechanism for the analysis, and three key variables were considered:
      effectiveness, feasibility, and operational expense. From the perspective of
      effectiveness, the TRICARE strategy demonstrated an ability to provide a slightly
      larger percentage of the requested replacement personnel. With regard to
      feasibility, both strategies were feasible in that both could provide
      replacements for the duration of the 270-day deployment and within an established
      180-day report date. Operational expense was a decisive factor with the reserve
      component option significantly less costly than the TRICARE alternative.
      Weaknesses and strengths of each option were identified and discussed, and
      alternatives were recommended.

PMID- 14964497
TI  - Military training and humanitarian and civic assistance.
AB  - Although the purpose of the Department of Defense humanitarian and civic
      assistance (HCA) projects is training, there is no system to evaluate HCA
      training or humanitarian effectiveness. Few after-action reports (AARs) document
      the number of personnel trained, skills taught, or proficiency before and after
      HCAs. Nevertheless, HCAs are positively viewed by participants and offer great
      potential for training service personnel as well as donors, expatriates, and host
      nation representatives. Linking unit training calendars with HCA projects and
      vice versa, would improve both projects and training. Mission essential tasks
      should be incorporated into HCAs, and conversely, HCAs into training. Training
      objectives should be clearly stated early in the planning and shared with all
      participants (subject to security). Proficiency to training standards and
      performance to international humanitarian standards should be documented in after
      action reports. Mandatory after-action reporting (ideally, in a standardized,
      easily retrievable format that supports postproject analysis) should be
      implemented. Reported training benefits of medical HCAs include a large number of
      patients treated in a short amount of time, often under austere conditions, and
      the opportunity to treat diseases of military importance that are not endemic in
      the United States. The vast majority of medical HCAs have involved direct patient
      care, but this scope should be expanded to include public health-oriented
      developmental and infrastructure-building projects that would provide lasting
      humanitarian benefits and training for additional personnel and units.

PMID- 14964498
TI  - Developing a child safety seat program.
AB  - The Car Seat Committee at our facility was formed in April 2000 to implement the
      American Academy of Pediatrics policy statement and recommendations for "Safe
      Transport of Newborns at Hospital Discharge." This study details the program
      developed at our facility to implement the American Academy of Pediatrics
      recommendations. In addition to the development of policies, the goals of the
      committee included: patient and staff education, marketing car seat information,
      community outreach, and research/reporting. The many initiatives and innovations
      of the committee enabled the hospital to create a solid foundation of child
      passenger safety. As a result of the actions of our committee, the Safety
      Restraint Coalition of the State of Washington designated the committee as a
      Child Passenger Safety Team, which is believed to be the first military team in
      the nation.

PMID- 14964499
TI  - Performance of military-trained physician assistants on the physician assistant
      national certification examination.
AB  - Although the first physician assistant (PA) program was born at a civilian
      academic institution, the impact of the military was immediately obvious as
      evidenced by the entire first class of PA students being Vietnam veteran Navy
      Corpsmen. Following initiation of the PA profession, the armed services
      established their own PA training programs that were eventually consolidated into
      a single interservice program in 1996. The mission of the Interservice PA Program
      is to produce high-quality PAs prepared to provide medical care in not only the
      traditional clinical arena but in the more unique situations seen in both
      peacetime and wartime military settings. PAs must complete an approved formal
      training program encompassing didactic and clinical training and pass a national
      certification examination to be licensed to practice. Pass rates are a key
      measure of the quality of a training program. We compared the national
      certification examination pass rates for our program with those of accredited
      civilian programs. Graduates of our program had a significantly higher pass rate
      and higher average scores than their civilian counterparts. These results are due
      to the strength of the program and faculty as well as the considerable hard work
      and dedication of the students who are drawn from a community that is, in many
      ways, non-traditional compared with other PA programs. These results demonstrate
      that the military training of PAs continues to provide high-quality health care
      providers who perform above their civilian-trained counterparts.

PMID- 14964500
TI  - Changes in dental classification during the first 4 years of military service.
AB  - OBJECTIVE: The objective of this study was to examine the way in which the oral
      health of recruits changed during the 4 years immediately after entry on active
      duty. METHODS: In 1998, 1,331 dental records of recruits in the 1994 Tri-Service
      Comprehensive Oral Health Survey were located, and treatment data were analyzed.
      RESULTS: Class 1, treatment complete or no treatment indicated, was achieved by
      61.2% (95% confidence interval, 58.4-64.0) of service members during the 4-year
      study period. Army, Navy, and Marine Corps percentages did not significantly
      differ in the range of 50% to 60%. The Air Force was significantly higher at
      89.5% achieving class 1. CONCLUSIONS: All services were successful in achieving
      and maintaining operational readiness among 1994 recruits who spent 93% of their
      first 4 years of military service in a deployable oral health status (class 1 or
      2). A significant number of recruits (38.8%) never achieved complete oral health
      (class 1).

PMID- 14964501
TI  - Epithelioid sarcoma of the thumb associated with hydrazine fuel exposure: a case
      report.
AB  - Hydrazine fuels are commonly used propellants for missiles and tactical jet
      aircraft used by the U.S. Air Force and the National Aeronautical and Space
      Administration. Hydrazine fuels are known to cause cancer after respiratory
      exposure or ingestion in laboratory animals and humans. Although hydrazine is
      known to cause skin irritation, there are no published reports describing cancer
      developing after cutaneous exposure to hydrazine in humans. Hydrazine is known to
      cause cancer in animals after skin exposure and is used to induce angiosarcomas
      in mice after cutaneous exposure. We present a case of an epithelioid sarcoma
      developing in the thumb of a patient after repeated exposure to hydrazine fuel.
      We hypothesize that the epithelioid sarcoma is a consequence of cutaneous
      exposure to hydrazine fuel. Continued efforts to develop less toxic alternative
      fuels and increased personal protection from occupational exposure are highly
      recommended.

PMID- 14964502
TI  - Soldier load carriage: historical, physiological, biomechanical, and medical
      aspects.
AB  - This study reviews historical and biomedical aspects of soldier load carriage.
      Before the 18th century, foot soldiers seldom carried more than 15 kg while on
      the march, but loads have progressively risen since then. This load increase is
      presumably due to the weight of weapons and equipment that incorporate new
      technologies to increase protection, firepower, communications, and mobility.
      Research shows that locating the load center of mass as close as possible to the
      body center of mass results in the lowest energy cost and tends to keep the body
      in an upright position similar to unloaded walking. Loads carried on other parts
      of the body result in higher energy expenditures: each kilogram added to the foot
      increases energy expenditure 7% to 10%; each kilogram added to the thigh
      increases energy expenditure 4%. Hip belts on rucksacks should be used whenever
      possible as they reduce pressure on the shoulders and increase comfort. Low or
      mid-back load placement might be preferable on uneven terrain but high load
      placement may be best for even terrain. In some tactical situations, combat load
      carts can be used, and these can considerably reduce energy expenditure and
      improve performance. Physical training that includes aerobic exercise, resistance
      training targeted at specific muscle groups, and regular road marching can
      considerably improve road marching speed and efficiency. The energy cost of
      walking with backpack loads increases progressively with increases in weight
      carried, body mass, walking speed, or grade; type of terrain also influences
      energy cost. Predictive equations have been developed, but these may not be
      accurate for prolonged load carriage. Common injuries associated with prolonged
      load carriage include foot blisters, stress fractures, back strains,
      metatarsalgia, rucksack palsy, and knee pain. Load carriage can be facilitated by
      lightening loads, improving load distribution, optimizing load-carriage
      equipment, and taking preventive action to reduce the incidence of injury.

PMID- 14964503
TI  - Outbreak of rove beetle (Staphylinid) pustular contact dermatitis in Pakistan
      among deployed U.S. personnel.
AB  - Deployed military personnel are often faced with a variety of exposures
      unfamiliar to U.S. physicians. This is the first report to describe an outbreak
      of a pustular disease among U.S. personnel deployed to Pakistan in support of
      Operation Enduring Freedom. Up to 10% of the base population was afflicted with a
      pustular eruption and an accompanying halo of erythema. A retrospective chart
      review and ongoing patient care resulted in 191 cases. Various therapies were
      used, including "watchful waiting." Gradual resolution occurred with residual
      area(s) of hypo- or hyperpigmentation. An irritant contact dermatitis was
      suspected based upon clinical presentation; staphylinid (rove) beetles were
      implicated. Rove beetle dermatitis from a pederin toxin has occurred in other
      parts of the world but has not been previously reported in Pakistan. We discuss
      the nature and progression of the dermatitis, treatments, outcomes, measures to
      control exposures, and the implications of such outbreaks.

PMID- 14964504
TI  - Musculoskeletal war wounds during Operation BRAVA in Sri Lanka.
AB  - Operation BRAVA (Blast Resuscitation and Victim Assistance) was conceived as a
      means of conducting humanitarian assistance, education, and training in the acute
      surgical management of land mine and other blast injuries. The first Operation
      BRAVA mission was carried out in Sri Lanka during 1998 at a time of civil war
      between government forces and Tamil separatists. Thirty-seven patients with
      orthopedic war wounds were seen during this mission because of the fighting.
      Exploding ordnance injured 24 patients (65%), and 13 patients (35%) sustained
      gunshot wounds. Sixty-seven percent of explosive injuries were from mortar
      rounds, and the remainder was from a variety of detonating munitions. Twenty-two
      patients (59%) sustained injuries to one or both lower limbs, and compartment
      syndrome of the leg developed in two of these patients as a result of multiple
      fragment injuries. Nine patients (24%) sustained concomitant neurological or
      vascular injuries. Operation BRAVA provided a novel approach to enhancing the
      combat medical skills of U.S. military personnel and was successful in developing
      working relationships with host country medical professionals, facilitating
      participation in the care of wounded patients, and establishing a framework upon
      which future BRAVA teams might build.

PMID- 14964505
TI  - Morphological and motor-endurance changes are highly related in Croatian navy
      male recruits.
AB  - A certain decrease of the physical fitness status during the second phase of a
      three-phase navy recruit training was observed in an experimental physical
      training program (PTP) performed by Croatian navy recruits in 2000. The
      morphological status (MS) and motor-endurance status (MES) changes in the status
      of these variables during the course of this study, and the influence or
      association of MS changes on MES were observed in 307 male navy recruits at the
      beginning and at the end of specialist navy training. The total sample was
      divided into two groups: E group (n = 199) performed experimental PTP and C group
      (n = 108) performed official PTP. Analysis of the variance between initial and
      final testing and the canonical analysis between MS changes and MES changes were
      calculated. Results show that the experimental PTP was more effective than the
      official PTP in improving MS and increasing MES. These results support for
      reprogramming the official PTP during the specialist-training period to make it a
      more effective tool for military readiness.

PMID- 14964506
TI  - Critical illness myopathy associated with hyperthyroidism.
AB  - A 51-year-old woman was admitted to the intensive care unit for exacerbation of
      chronic obstructive pulmonary disease. She received antibiotics, neuromuscular
      blocking agents, and steroids. After 8 days in the intensive care unit, she was
      noted to be severely weak, her serum creatine kinase had risen to 1,692 U/L
      (normal, 20-220 U/L), and a muscle biopsy was consistent with critical illness
      myopathy. As a result of evaluating for resting tachycardia, the patient was
      found to be hyperthyroid. Her weakness rapidly improved within 1 month after
      treatment of her hyperthyroidism with iodine-131 and methimazole. The metabolic
      alterations associated with hyperthyroidism may enhance the risk of developing
      critical illness myopathy after the administration of antibiotics, neuromuscular
      blocking agents, and steroids in the intensive care unit.

PMID- 14964507
TI  - Navy Hearing Conservation Program: 1995-1999 retrospective analysis of threshold
      shifts for age, sex, and officer/enlisted status.
AB  - This study provides a cross-sectional, population-based analysis of significant
      threshold shifts (STS) from over 83,000 audiograms on active duty members in the
      Navy Hearing Conservation Program Database for 1995-1999. Crude STS rates were
      lower for women than men (odds ration [OR], 0.82; 95% confidence interval [CI],
      0.76-0.89; p = 0.0000) and lower for officer than enlisted (OR, 0.71; 95% CI,
      0.66-0.76; p = 0.000000). STS rates also increased significantly with increasing
      age (chi2 for trend, 134; p = 0.0000). Compared with historical information, STS
      rates for officers were significantly lower (OR, 0.23; 95% CI, 0.18-0.27; p =
      0.00000). Adjustment by logistic regression found STS rates were lower for women
      (OR, 0.837; 95% CI, 0.773-0.905; p = 0.000) and officer status (OR, 0.670; 95%
      CI, 0.619-0.725; p = 0.0000), and increased significantly with age. These
      findings warrant further investigation because they have programmatic
      implications on Navy hearing conservation and force health protection.

PMID- 14964508
TI  - Splenic hydatid cysts in a 20-year-old soldier.
AB  - Hydatid disease is a parasitic infection of humans and herbivorous animals caused
      by Echinococcus granulosus. A 20-year-old male soldier from Booshehr province
      police center was admitted with left upper quadrant pain that began 1 year before
      admission. Sonography disclosed an echogenic mass measuring 14 x 16 cm near the
      spleen and kidneys; a computed tomography scan confirmed it as a hypodense mass
      of the spleen that was 16 x 17 x 18 cm in dimension. Casoni skin test and
      indirect fluorescent antibody were positive. Through laparatomy, a splenectomy
      was successfully performed.

PMID- 14964509
TI  - Evaluation of techniques for intravenous catheter and tubing fixation.
AB  - OBJECTIVE: The aim of this study was to examine two techniques intended to
      prevent accidental displacement of intravenous catheters after proper
      establishment of infusion line access. METHODS: After catheter insertion and
      taping in position, fixation with gauze roll sequentially wrapped around the limb
      across which the tubing has been extended was compared with the use of a
      polyethylene roll manipulated by an attached "handle." The experimentation was
      performed on medical personnel serving as live models. RESULTS: Thirty-eight
      trials were conducted with 19 of each fixation technique. The variables measured
      were: time consumption, convenience, general satisfaction, and success score of
      the fixation. All of the measurements showed that the polyethylene roll was
      significantly the superior of the two methods. Despite forceful tugging of the
      tubing, polyethylene fixation virtually prevented any displacement whatsoever and
      was more than twice as rapid. CONCLUSIONS: We demonstrate a novel device allowing
      faster and more efficacious fixation of the infusion drip tubing and catheter
      suggested as the technique of choice in emergency medical field care.

PMID- 14964510
TI  - A 20-year-old-Army private presenting with chronic monarticular arthritis.

PMID- 14964511
TI  - Infectious diarrhea, both viral and bacterial.

PMID- 14964512
TI  - Infectious mononucleosis (IM) associated rupture of the spleen.

PMID- 14964513
TI  - Social work in a multicultural society.

PMID- 14964514
TI  - Multicultural development in human services agencies: challenges and solutions.
AB  - Comprehensive multicultural organizational development (MCOD) is increasingly
      necessary in human services agencies. This article presents results from an
      exploratory study that identified challenges and solutions to MCOD, against the
      backdrop of daily realities of agency life. The author conducted interviews with
      20 consultants and 20 practitioners experienced in MCOD. Qualitative analysis
      revealed four challenges--socioeconomic environment, organizational dynamics,
      conceptualization of the change effort, and consultant competence; and four
      solutions--collaborative environmental relations, leadership development,
      assessment and planning, and consultant selection. Results suggest the
      complexities of MCOD and ways that human services agencies can sustain such
      efforts.

PMID- 14964515
TI  - Race, place, space: meanings of cultural competence in three child welfare
      agencies.
AB  - Despite a consensus on the need to take culture into account in social services
      delivery, remarkably little data is available on the processes of culturally
      competent organizational development. This article addresses how workers,
      supervisors, and managers involved in culturally competent organizational change
      perceive the goals and dilemmas of these efforts during the initial stages. Data
      are drawn from three nonprofit child and family agencies in one metropolitan
      area. The data demonstrate that cultural competence means disparate and
      conflicting things to differently positioned members of each organization. The
      authors argue that conflicts may be inherent in the process of culturally
      competent organizational development, particularly to the extent that such
      efforts attempt to redistribute power in the workplace. Efforts to develop
      cultural competence must identify, surface, and renegotiate these conflicts.

PMID- 14964516
TI  - Working with Hindu clients in a spiritually sensitive manner.
AB  - Although social work is witnessing growing interest in spiritual and religious
      issues, little guidance has appeared in the literature to assist practitioners in
      addressing the unique spirituality of rapidly increasing non-Western populations.
      This article discusses the significant cultural/spiritual beliefs, practices, and
      values of Hindus, the largest Asian religion in the United States. Possible
      conflicts emanating from the lack of congruence between the values of Hindu
      consumers, derived from the dharma--the sacred moral order--and the values of
      social workers, derived from a Western Enlightenment discourse, are highlighted.
      The author offers practice-oriented suggestions to facilitate cultural
      sensitivity and to further integrate the spiritual strengths of Hindus into the
      clinical dialogue.

PMID- 14964517
TI  - Assumptions of Asian American similarity: the case of Filipino and Chinese
      American students.
AB  - The conventional research model of clustering ethnic groups into four broad
      categories risks perpetuating a pedagogy of stereotypes in social work policies
      and practice methods. Using an elaborated research model, this study tested the
      assumption of cultural similarity of Filipino and Chinese American college
      students by examining attitudes, perceptions, and beliefs related to dating
      violence. The sample included Chinese, Filipino, Hispanic, and white
      undergraduate students from a large urban university. Findings suggest that
      Filipino students are more similar to white students than to Chinese students.
      Regardless of ethnic group, women had more similarities with one another than men
      in their attitudes toward women. The findings were mixed regarding definitions
      and justifications of violence.

PMID- 14964518
TI  - Treatment adherence among Native Hawaiians living with HIV.
AB  - Cultural competence is essential in helping people living with HIV cope with the
      biopsychosocial and spiritual challenges associated with this illness. Efforts to
      understand the relationship of cultural values and social support practices to
      health-related behavior have rarely been more critical than in the emerging issue
      of treatment adherence to highly active antiretroviral therapy (HAART), a
      multidrug regime that potentially extends the longevity of those living with HIV
      but may be complex to manage. This article highlights findings from a study on
      health beliefs, perceived social support, and HAART adherence among Native
      Hawaiians, a group with historic difficulty in using Western health care services
      because of cultural conflict. Implications are suggested for social workers and
      other health care providers in the development of interventions that use cultural
      preferences to support HAART adherence.

PMID- 14964519
TI  - Africentric youth and family rites of passage program: promoting resilience among
      at-risk African American youths.
AB  - This article examines the effects of an Africentric youth and family rites of
      passage program on at-risk African American youths and their parents. Data were
      obtained from a three-year evaluation of a youth rites of passage demonstration
      project using therapeutic interventions based on Africentric principles. At-risk
      African American boys between ages 11.5 and 14.5 years with no history of
      substance abuse were referred from the criminal justice system, diversion
      programs, and local schools. The evaluation revealed that participating youths
      exhibited gains in self-esteem and accurate knowledge of the dangers of drug
      abuse. Although the differences were not statistically significant, parents
      demonstrated improvements in parenting skills, racial identity, cultural
      awareness, and community involvement. Evidence from interviews and focus groups
      suggests that the program's holistic, family-oriented, Africentric, strengths
      based approach and indigenous staff contributed to its success.

PMID- 14964520
TI  - Enhancing psychosocial competence among black women in college.
AB  - Many black women in the United States experience unique stressors that often
      impede their ability to interact and cope effectively in their psychosocial
      environment. The study in this article examined factors affecting the ability of
      black women to cope with everyday stressors and to master situations that induce
      psychological distress. Using an experimental design composed of an intervention
      group and a nontreatment control group with pretest and posttest measures, the
      study tested three hypotheses concerning the effectiveness of a psychoeducational
      group intervention involving 58 undergraduate black college women. Results
      revealed that after the eight-week group program the level of perceived stress
      among intervention group participants was reduced significantly compared with
      members of the control group. The difference remained statistically significant
      after control variables were taken into account. However, the data failed to
      support the hypotheses that the intervention would have a statistically
      significant effect on reducing the participants' external locus of control and
      increasing active coping. Although this study was conducted with a small sample
      of black college women, the findings offer preliminary data on the effectiveness
      of culture-based group interventions with black women aimed at enhancing
      psychosocial competence.

PMID- 14964521
TI  - Coming out of the closet: opening agencies to gay and lesbian adoptive parents.
AB  - Gay men and lesbians often encounter barriers when they pursue adoption. Adoption
      workers are expected to make decisions regarding child placement using the best
      interest standard. However, this decision-making model does not adequately
      consider intrapersonal, interpersonal, and organizational factors that affect the
      use of the standard. This article examines the best interest standard and makes
      practice recommendations to increase the accessibility of adoptions for gay and
      lesbian applicants.

PMID- 14964522
TI  - Empowering African American women informal caregivers: a literature synthesis and
      practice strategies.
AB  - Through a synthesis of literature on caregiving, empowerment, social
      inequalities, and racial disparities in health and income, the authors built an
      argument for African American women caregivers' vulnerability to powerlessness
      and the applicability of an empowerment approach to social work practice with
      these caregivers. The article discusses two realities of African American women
      caregivers' experiences (strong coping and vulnerability) and two relevant
      theoretical frameworks (stress and coping and empowerment frameworks) for framing
      these experiences. Drawing on empowerment and other relevant literature, the
      authors recommend three practice strategies with these caregivers.

PMID- 14964523
TI  - Learning that an adolescent child is gay or lesbian: the parent experience.
AB  - Increasing numbers of adolescents are disclosing their sexual orientation to
      parents at an earlier stage of the family life cycle than their predecessors.
      Although we know that parents are coexperiencing the range of difficulties
      reflected in reports of gay and lesbian youths after disclosure, there is a
      paucity of investigative research exploring the parents' side of adolescent
      disclosure. The precarious nature of adolescence places these parents in a
      different set of circumstances than parents of gay adults. This article draws
      from a study that examined the parent experience at the adolescent stage of the
      family life cycle. The study explored the meaning parents ascribe to learning
      that an adolescent is gay or lesbian, how adolescent disclosure affects the
      solidarity of the parent-child relationship, and what interventions support
      healthy parent adjustment. Implications for competent social work practice with
      parents of gay and lesbian adolescents are addressed.

PMID- 14964524
TI  - Short-term intercultural psychotherapy: ethnographic inquiry.
AB  - This article examines the challenges specific to short-term intercultural
      treatments and recently developed approaches to intercultural treatments based on
      notions of cultural knowledge and cultural competence. The article introduces
      alternative approaches to short-term intercultural treatments based on
      ethnographic inquiry adapted for clinical practice. Such approaches allow
      clinicians conducting short-term intercultural treatments to foreground clients'
      indigenous conceptions of selfhood, mind, relationship, and emotional
      disturbance, and thus to more fully grasp their internal, interpersonal, and
      external worlds. This article demonstrates the uses of clinically adapted
      ethnographic inquiry in three short-term intercultural cases.

PMID- 14964525
TI  - Mutual support groups for long-term recipients of TANF.
AB  - This study examined the effect of involvement in mutual support groups on long
      term recipients of Temporary Assistance for Needy Families (TANF) and other
      vulnerable individuals. From qualitative interviews with nine group members, the
      study identified key themes, benefits, and barriers related to involvement in the
      groups. Content analysis of the data revealed insights about characteristics of
      effective self-help and mutual support groups, which social workers and other
      professionals can use to develop effective support groups in the future.
      Participants discussed benefits for themselves and their families, such as
      enhanced parenting and social skills, increased knowledge, and enhanced self
      esteem.

PMID- 14964526
TI  - Social work theory.

PMID- 14964527
TI  - Harpin inactivates mitochondria in Arabidopsis suspension cells.
AB  - Harpin is a well-known proteinaceous bacterial elicitor that can induce an
      oxidative burst and programmed cell death in various host plants. Given the
      demonstrated roles of mitochondria in animal apoptosis, we investigated the
      effect of harpin from Pseudomonas syringae on mitochondrial functions in
      Arabidopsis suspension cells in detail. Fluorescence microscopy in conjunction
      with double-staining for reactive oxygen species (ROS) and mitochondria suggested
      co-localization of mitochondria and ROS generation. Plant defense responses or
      cell death after pathogen attack have been suggested to be regulated by the
      concerted action of ROS and nitric oxide (NO). However, although Arabidopsis
      cells respond to harpin treatment with NO generation, time course analyses
      suggest that NO generation is not involved in initial responses but, rather, is a
      consequence of cellular decay. Among the fast responses we observed was a
      decrease of the mitochondrial membrane potential deltapsim, and, possibly as a
      direct consequence, of ATP production. Furthermore, treatment of Arabidopsis
      cells with harpin protein induced a rapid cytochrome C release from mitochondria
      into the cytosol, which is regarded as a hallmark of programmed cell death or
      apoptosis. Northern and DNA array analyses showed strong induction of protecting
      or scavenging systems such as alternative oxidase and small heat shock proteins,
      components that are known to be associated with cellular stress responses. In
      sum, the presented data suggest that harpin inactivates mitochondria in
      Arabidopsis cells.

PMID- 14964528
TI  - Overexpression of (At)NPR1 in rice leads to a BTH- and environment-induced lesion
      mimic/cell death phenotype.
AB  - Systemic acquired resistance (SAR) is an inducible defense response that protects
      plants against a broad spectrum of pathogens. A central regulator of SAR in
      Arabidopsis is NPR1 (nonexpresser of pathogenesis-related genes). In rice,
      overexpression of Arabidopsis NPR1 enhances plant resistance to the bacterial
      pathogen Xanthomonas oryzae pv. oryzae. This report demonstrates that
      overexpression of (At)NPR1 in rice also triggers a lesion-mimic/cell death (LMD)
      phenotype. The LMD phenotype is environmentally regulated and heritable. In
      addition, the development of lesions and death correlates with the expression of
      rice defense genes and the accumulation of hydrogen peroxide. Application of the
      salicylic acid (SA) analog, benzo(1,2,3) thiadiazole-7-carbothioc acid S-methyl
      ester (BTH), potentiates this phenotype Endogenous SA levels are reduced in rice
      overexpressing (At)NPR1 when compared with wildtype plants, supporting the idea
      that (At)NPR1 may perceive and modulate the accumulation of SA. The association
      of (At)NPR1 expression in rice with the development of an LMD phenotype suggests
      that (At)NPR1 has multiple roles in plant stress responses that may affect its
      efficacy as a transgenic tool for engineering broad-spectrum resistance.

PMID- 14964529
TI  - Importance of opgHXcv of Xanthomonas campestris pv. vesicatoria in host-parasite
      interactions.
AB  - Tn5 insertion mutants of Xanthomonas campestris pv. vesicatoria were inoculated
      into tomato and screened for reduced virulence. One mutant exhibited reduced
      aggressiveness and attenuated growth in planta. Southern blot analyses indicated
      that the mutant carried a single Tn5 insertion not associated with previously
      cloned pathogenicity-related genes of X. campestris pv. vesicatoria. The wild
      type phenotype of this mutant was restored by one recombinant plasmid (pOPG361)
      selected from a genomic library of X. campestris pv. vesicatoria 91-118. Tn3-gus
      insertion mutagenesis and sequence analyses of a subclone of pOPG361 identified a
      1,929-bp open reading frame (ORF) essential for complementation of the mutants.
      The predicted protein encoded by this ORF was highly homologous to the previously
      reported pathogenicity-related HrpM protein of Pseudomonas syringae pv. syringae
      and OpgH of Erwinia chrysanthemi. Based on homology, the new locus was designated
      opgHXcv. Manipulation of the osmotic potential in the intercellular spaces of
      tomato leaves by addition of mannitol at low concentrations (25 to 50 mM)
      compensates for the opgHXcv mutation.

PMID- 14964530
TI  - Identification and characterization of a well-defined series of coronatine
      biosynthetic mutants of Pseudomonas syringae pv. tomato DC3000.
AB  - To identify Pseudomonas syringae pv. tomato genes involved in pathogenesis, we
      carried out a screen for Tn5 mutants of P. syringae pv. tomato DC3000 with
      reduced virulence on Arabidopsis thaliana. Several mutants defining both known
      and novel virulence loci were identified. Six mutants contained insertions in
      biosynthetic genes for the phytotoxin coronatine (COR). The P. syringae pv.
      tomato DC3000 COR genes are chromosomally encoded and are arranged in two
      separate clusters, which encode enzymes responsible for the synthesis of
      coronafacic acid (CFA) or coronamic acid (CMA), the two defined intermediates in
      COR biosynthesis. High-performance liquid chromatography fractionation and
      exogenous feeding studies confirmed that Tn5 insertions in the cfa and cma genes
      disrupt CFA and CMA biosynthesis, respectively. All six COR biosynthetic mutants
      were significantly impaired in their ability to multiply to high levels and to
      elicit disease symptoms on A. thaliana plants. To assess the relative
      contributions of CFA, CMA, and COR in virulence, we constructed and characterized
      cfa6 cmaA double mutant strains. These exhibited virulence phenotypes on A.
      thalliana identical to those observed for the cmaA or cfa6 single mutants,
      suggesting that reduced virulence of these mutants on A. thaliana is caused by
      the absence of the intact COR toxin. This is the first study to use biochemically
      and genetically defined COR mutants to address the role of COR in pathogenesis.

PMID- 14964531
TI  - Establishment of a functional genomics platform for Leifsonia xyli subsp. xyli.
AB  - Leifsonia xyli subsp. xyli, the causal agent of ratoon stunting disease in
      sugarcane, is a xylem-limited, nutritionally fastidious, slow growing, gram
      positive coryneform bacterium. Because of the difficulties in growing this
      bacterium in pure culture, little is known about the molecular mechanisms of
      pathogenesis. Currently, the genome sequence of L. xyli subsp. xyli is being
      completed by the Agronomical and Environmental Genomes group from the
      Organization for Nucleotide Sequencing and Analysis in Brazil. To complement this
      work, we produced 712 Lxx::Tn4431 transposon mutants and sequenced flanking
      regions from 383 of these, using a rapid polymerase chain reaction-based
      approach. Tn4431 insertions appeared to be widespread throughout the L. xyli
      subsp. xyli genome; however, there were regions that had significantly higher
      concentrations of insertions. The Tn4431 mutant library was screened for
      individuals unable to colonize sugarcane, and one noncolonizing mutant was found.
      The mutant contained a transposon insertion disrupting two open reading frames
      (ORF), one of which had homology to an integral membrane protein from
      Mycobacterium leprae. Sequencing of the surrounding regions revealed two operons,
      pro and cyd, both of which are believed to play roles in disease. Complementation
      studies were carried out using the noncolonizing Lxx::Tn4431 mutant. The
      noncolonizing mutant was transformed with a cosmid containing 40 kbp of wild-type
      sequence, which included the two ORF disrupted in the mutant, and several
      transformants were subsequently able to colonize sugarcane. However, analysis of
      each of these transformants, before and after colonization, suggests that they
      have all undergone various recombinant events, obscuring the roles of these ORF
      in L. xyli subsp. xyli pathogenesis.

PMID- 14964532
TI  - Analysis of Erwinia chrysanthemi EC16 pelE::uidA, pelL::uidA, and hrpN::uidA
      mutants reveals strain-specific atypical regulation of the Hrp type III secretion
      system.
AB  - The plant pathogen Erwinia chrysanthemi produces a variety of factors that have
      been implicated in its ability to cause soft-rot diseases in various hosts. These
      include HrpN, a harpin secreted by the Hrp type III secretion system; PelE, one
      of several major pectate lyase isozymes secreted by the type II system; and PelL,
      one of several secondary Pels secreted by the type II system. We investigated
      these factors in E. chrysanthemi EC16 with respect to the effects of medium
      composition and growth phase on gene expression (as determined with uidA fusions
      and Northern analyses) and effects on virulence. pelE was induced by
      polygalacturonic acid, but pelL was not, and hrpN was expressed unexpectedly in
      nutrient-rich King's medium B and in minimal salts medium at neutral pH. In
      contrast, the effect of medium composition on hrp expression in E. chrysanthemi
      CUCPB1237 and 3937 was like that of many other phytopathogenic bacteria in being
      repressed in complex media and induced in acidic pH minimal medium. Northern blot
      analysis of hrpN and hrpL expression by the wild-type and hrpL::omegaCmr and
      hrpS::omegaCmr mutants revealed that hrpN expression was dependent on the HrpL
      alternative sigma factor, whose expression, in turn, was dependent on the HrpS
      putative sigma54 enhancer binding protein. The expression of pelE and hrpN
      increased strongly in late logarithmic growth phase. To test the possible role of
      quorum sensing in this expression pattern, the expI/expR locus was cloned in
      Escherichia coli on the basis of its ability to direct production of acyl
      homoserine lactone and then used to construct expI mutations in pelE::uidA,
      pelL::uidA, and hrpN::uidA Erwinia chrysanthemi strains. Mutation of expI had no
      apparent effect on the growth-phase-dependent expression of hrpN and pelE, or on
      the virulence of E. chrysanthemi in witloof chicory leaves. Overexpression of
      hrpN in E. chrysanthemi resulted in approximately 50% reduction of lesion size on
      chicory leaves without an effect on infection initiation.

PMID- 14964533
TI  - Host-specific generation and maintenance of Tomato bushy stunt virus defective
      interfering RNAs.
AB  - The accumulation of Tomato bushy stunt virus (TBSV) defective interfering RNAs
      (DIs) has been observed in several species of plants, but the involvement of host
      specific processes and the functional role of DIs are still poorly understood. In
      this study, the accumulation of DIs was compared after several passages of TBSV
      through Nicotiana benthamiana and pepper (Capsicum annuum). As anticipated,
      passages of wild-type TBSV through N. benthamiana resulted in the accumulation of
      significant levels of TBSV DIs, which caused symptom attenuation and prevented
      the plants from lethal necrosis. On the contrary, TBSV infection of pepper plants
      caused severe local and systemic chlorosis, but continuous virus passages did not
      result in detectable levels of DIs accumulation. In addition, the inoculation of
      pepper plants with a mixture of helper virus and DI either from in vitro
      generated transcripts or from infected N. benthamiana did not yield DI in upper
      pepper leaves. Our cumulative results suggest that complex host-specific
      determinants play an important role in TBSV DI generation and their subsequent
      maintenance and accumulation.

PMID- 14964535
TI  - Cell surface interactions of Rhizobium bacteroids and other bacterial strains
      with symbiosomal and peribacteroid membrane components from pea nodules.
AB  - Samples of Rhizobium bacteroids isolated from pea nodule symbiosomes reacted
      positively with a monoclonal antibody recognizing N-linked glycan epitopes on
      plant glycoproteins associated with the peribacteroid membrane and peribacteroid
      fluid. An antiserum recognizing the symbiosomal lectin-like glycoprotein PsNLEC-1
      also reacted positively. Samples of isolated bacteroids also reacted with an
      antibody recognizing a glycolipid component of the peribacteroid membrane and
      plasma membrane. Bacterial cells derived from free-living cultures then were
      immobilized on nitrocellulose sheets and tested for their ability to associate
      with components of plant extracts derived from nodule fractionation. A positive
      antibody-staining reaction indicated that both PsNLEC-1 and membrane glycolipid
      had become associated with the bacterial surface. A range of rhizobial strains
      with mutants affecting cell surface polysaccharides all showed similar
      interactions with PsNLEC-1 and associated plant membranes, with the exception of
      strain B659 (a deep-rough lipopolysaccharide mutant of Rhizobium leguminosarum).
      However, the presence of a capsule of extracellular polysaccharide apparently
      prevented interactions between rhizobial cells and these plant components. The
      importance of a close association between peribacteroid membranes, PsNLEC-1, and
      the bacterial surface is discussed in the context of symbiosome development.

PMID- 14964536
TI  - Tobacco transgenic for the flax rust resistance gene L expresses allele-specific
      activation of defense responses.
AB  - Tobacco was transformed with three different alleles (L2, L6, and L10) of the
      flax rust resistance gene L, a member of the toll interleukin-1 receptor,
      nucleotide-binding site, leucine-rich repeat (TIR-NBS-LRR) class of plant disease
      resistance genes. L6 transgenics had a stunted phenotype, expressed several
      defense response genes constitutively, and had increased resistance to the fungus
      Cercospora nicotianae and the oomycete Phytophthora parasitica pv. nicotianae. L2
      and L10 transgenics, with one exception for L10, did not express these
      phenotypes, indicating that the activation of tobacco defense responses is L6
      allele-specific. The phenotype of the exceptional L10 transgenic plant was
      associated with the presence of a truncated L10 gene resulting from an aberrant T
      DNA integration. The truncated gene consisted of the promoter, the complete TIR
      region, and 39 codons of the NBS domain fused inframe to a tobacco
      retrotransposon-like sequence. A similar truncated L10 gene, constructed in
      vitro, was transiently expressed in tobacco leaves and gave rise to a strong
      localized necrotic reaction. Together, these results suggest that defense
      signaling properties of resistance genes can be expressed in an allele-specific
      and pathogen-independent manner when transferred between plant genera.

PMID- 14964537
TI  - Hormonal changes after Roux-en Y gastric bypass for morbid obesity and the
      control of type-II diabetes mellitus.
AB  - Morbid obesity (MO) is associated with diabetes mellitus-type II (DM-II). Roux-en
      Y gastric bypass (RNY) has been shown to normalize glucose intolerance in these
      patients through an incompletely understood mechanism. Gastrointestinal hormonal
      changes have been suggested as an explanation for resolution of DM II.
      Preoperatively, 20 MO patients with DM-II were evaluated for demographics and
      fasting levels of the following: glucose, insulin, C-peptide, glucagon, cortisol,
      gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). Each
      patient underwent RNY with a 15-cc gastric pouch and 150-cm Roux limb.
      Postoperatively, each of the variables was measured at 2 weeks, 6 weeks, and 12
      weeks and compared with the preoperative result using Student t test with
      significance, P = 0.05. Results are expressed as mean +/- SD. Twenty patients (5
      male and 15 female), age 40.3 +/- 7.9 years, weight 146.3 +/- 34.0 kg, height
      158.7 +/- 18.7 cm, and BMI 52.7 +/- 8.8, were enrolled in this IRB-approved
      protocol. Weight and BMI decreased progressively (117.5 +/- 26.9 kg and 47.0 +/-
      7.4, P = 0.01, respectively) during the study but reached significance only at 12
      weeks. Fasting plasma glucose decreased significantly within 2 weeks after RNY.
      Insulin and cortisol both approached, but never achieved, significant changes
      over 12 weeks. GLP-1 increased initially, but not significantly. GIP and C
      peptide both decreased significantly. Glucagon remained essentially unchanged
      over 12 weeks. RNY rapidly normalizes fasting plasma glucose in morbidly obese
      patients with DM-II. GIP, a gactor in the enteroinsulin axis, decreases and may
      play a role in the correction of DM-II after gastric bypass.

PMID- 14964534
TI  - Transcriptional responses of Paxillus involutus and Betula pendula during
      formation of ectomycorrhizal root tissue.
AB  - In order to obtain information on genes specifically expressed in the
      ectomycorrhizal symbiosis, 3,555 expressed sequence tags (ESTs) were analyzed
      from a cDNA library constructed from ectomycorrhiza formed between the
      basidiomycete Paxillus involutus and birch (Betula pendula). cDNA libraries from
      saprophytically growing fungus (3,964 ESTs) and from axenic plants (2,532 ESTs)
      were analyzed in parallel. By clustering all the EST obtained, a nonredundant set
      of 2,284 unique transcripts of either fungal or plant origin were identified. The
      expression pattern of these genes was analyzed using cDNA microarrays. The
      analyses showed that the plant and fungus responded to the symbiosis by altering
      the expression levels of a number of enzymes involved in carbon metabolism.
      Several plant transcripts with sequence similarities to genes encoding enzymes in
      the tricarboxylic cycle and electron transport chain were down regulated as
      compared with the levels in free-living roots. In the fungal partner, a number of
      genes encoding enzymes in the lipid and secondary metabolism were down regulated
      in mycorrhiza as compared with the saprophytically growing mycelium. A
      substantial number of the ESTs analyzed displayed significant sequence
      similarities to proteins involved in biotic stress responses, but only a few of
      them showed differential expression in the mycorrhizal tissue, including plant
      and fungal metallothioneins and a plant defensin homologue. Several of the genes
      that were differentially expressed in the mycorrhizal root tissue displayed
      sequence similarity to genes that are known to regulate growth and development of
      plant roots and fungal hyphae, including transcription factors and Rho-like
      GTPases.

PMID- 14964538
TI  - Blind Whipple resections for periampullary and pancreatic lesions.
AB  - Many patients with periampullary mass lesions lack a tissue diagnosis at referral
      despite advances in body imaging and aggressive biopsy techniques. This review
      evaluates a consecutive cohort of patients who underwent pancreatoduodenectomy
      (PD) with and without a diagnosis of malignancy. From 1990 to 2001, 121 patients
      underwent PD on a gastrointestinal surgical service by a single surgeon with a
      bias toward "blind" Whipple resections (BWR). Sixty-three per cent of the
      patients had obstructive jaundice with a mass on CT in 51 per cent. Fifty-three
      patients (44%) had a preoperative diagnosis of malignancy. Sixty-eight patients
      (56%) underwent a blind PD based on computed tomography (CT), ERCP, and clinical
      findings. After PD, 113 patients (94%) had a malignancy (46 pancreatic, 30
      ampullary, 13 cholangiocarcinoma, 9 neuroendocrine, 4 duodenal, 10 other). Of the
      68 patients (56%) who underwent a blind PD, 61 patients (90%) had a malignancy.
      Ten per cent of the BWR patients had a pathologic diagnosis of chronic
      inflammation/pancreatitis. Overall mortality was 3.3% (4 patients), with no
      deaths in the BWR group. In this review, clinical judgment was correct in 90 per
      cent of patients undergoing a "blind" PD without a prior diagnosis of malignancy.
      In patients with "potentially resectable" lesions (based on CT exam), biopsy
      information does not affect the choice of therapy since a negative biopsy still
      commits the patients to surgery. Combined CT and/or ERCP data with clinical
      findings leads most often to a correct diagnosis and procedure. These data
      question the practice of numerous biopsy attempts in patients with periampullary
      lesions.

PMID- 14964539
TI  - An argument against routine sentinel node mapping for DCIS.
AB  - Indications for sentinel lymph node mapping (SLNM) for patients with ductal
      carcinoma in situ (DCIS) of the breast are controversial. We reviewed our
      institutional experience with SLNM for DCIS to determine the node positive rate
      and clarify indications for nodal staging in patients with DCIS. Since 1998 we
      have used SLNM to stage breast cancer patients using both blue dye and
      radiocolloid. In DCIS patients, SLNM has been reserved for patients considered at
      high risk for harboring coexistent invasive carcinoma or treated by mastectomy.
      All sentinel nodes were evaluated with serial sectioning, hematoxylin and eosin
      staining, and immunohistochemical evaluation for cytokeratins. We identified 44
      patients with 46 cases of DCIS (two patients with bilateral disease). SLNM
      identified at least one sentinel node in all cases. In all cases, the sentinel
      node(s) were negative for axillary metastasis. We calculated the binomial
      probability of observing 0 of 46 cases as negative when the expected incidence
      according to published reports in the surgical literature was 13 per cent and
      found a P value of <0.01. Based on this case-series observation, we conclude SLNM
      should not be routinely performed for patients with DCIS. We now use SLNM only
      for DCIS patients treated by mastectomy.

PMID- 14964540
TI  - Serum lactic acid determines the outcomes of CT diagnosis of pneumatosis of the
      gastrointestinal tract.
AB  - Computed tomography (CT) diagnosis of pneumatosis involving the gastrointestinal
      tract can represent a broad range of clinical entities from a benign process to
      ischemic bowel. The purpose of this study is to define the significance and
      outcome of pneumatosis intestinalis (PI). All CT scans from 5/93 to 12/01 with
      the finding of PI were reviewed. Eighty-six CT scans had the finding of PI, with
      the colon being the most frequent location (51%), followed by small bowel (36%)
      and gastric (9%). Forty per cent of patients underwent surgery, with an overall
      mortality rate of 42 per cent and a surgical mortality rate of 47 per cent.
      Univariate analysis demonstrated significant correlation between serum lactic
      acid (LA) > 2.0 mmol/L [odds ratio (OR) = 23.4; 95% confidence interval (C.I.),
      7.21-75.92] and serum creatinine > 1.5 mg/dL (OR = 3.05; 95% C.I., 1.25-7.42)
      with mortality. Age was suggestive but not a significant risk factor for
      mortality (P = 0.09). Multivariate analysis found serum LA > 2.0 (OR = 30.37; 95%
      C.I., 7.31-126.2) to be the only significant predictor of mortality. CT diagnosis
      of PI is associated with significant in-hospital mortality, especially in the
      elderly. Serum LA level > 2.0 mmol/L at time of diagnosis is associated with a
      greater than 80 per cent mortality. Surgical consultation is necessary to
      determine which patients need urgent surgical intervention.

PMID- 14964541
TI  - Chloride/phosphate ratio in primary hyperparathyroidism.
AB  - The chloride/phosphate (Cl:PO4) ratio is known to help distinguish between the
      hypercalcemia of primary hyperparathyroidism (HPT) and hypercalcemia from other
      causes. The Cl:PO4 ratio of 106 patients with surgically proven primary HPT was
      compared with that of 126 normocalcemic healthy outpatients to examine its
      usefulness as a confirmatory test for primary HPT. The Cl:PO4 ratio was
      significantly higher in patients with HPT (42.5 +/- 7.0) compared with healthy
      controls (28.7 +/- 4.6). Patients with HPT and mild renal insufficiency (serum
      creatinine, 1.5-2.4 mg/dL) also showed a significant increase in the Cl:PO4 ratio
      (37.3 +/- 6.6) as did those with HPT with borderline elevations in serum calcium
      (calcium < 11; Cl:PO4, 40.3 +/- 5.6). A Cl:PO4 ratio > or = 33 is a reliable
      diagnostic test for primary HPT when compared with a normal population. The
      Cl:PO4 ratio is also of value in the evaluation of the patient with suspected HPT
      and borderline calcium elevation and those with mild renal impairment. These data
      suggest that an inexpensive Cl:PO4 ratio might replace serum parathormone assay
      as a confirmatory test in the evaluation of suspected primary HPT, especially for
      those patients in whom a localizing study (sestamibi scan) is obtained before
      neck exploration.

PMID- 14964542
TI  - Solid-pseudopapillary tumor of the pancreas: two cases in male patients.
AB  - Solid-pseudopapillary tumor (SPT) of the pancreas is a rare lesion with low
      malignant potential occurring predominantly in young women. This is a report of
      two cases in young male patients. Clinical data were retrieved retrospectively
      from a prospective database of patients with pancreatic tumors. The two patients
      were caucasian males, ages 34 years (Pt1) and 41 years (Pt2) at the time of
      diagnosis. Pt1 presented with intermittent epigastric pain, nausea, and vomiting.
      Computed tomography (CT) scan showed a 9-cm mass involving the pancreatic head.
      He underwent pancreaticoduodenectomy, with en bloc segmental colectomy due to
      mesocolon involvement. Pt2 was asymptomatic, diagnosed with abdominal mass by
      screening ultrasound. He had an 11-cm tumor involving the pancreatic tail
      encasing the splenic vessels on CT. He underwent distal pancreatectomy with
      splenectomy en bloc. Pathology in both cases was reviewed by staff pathologists
      as well as outside consultants. SPT is a rare tumor of the pancreas that is
      diagnosed primarily in young women. The cases presented here demonstrate SPT of
      the pancreas in two men. In both cases, the clinical presentation was relatively
      unremarkable. Both have had benign late postoperative courses, consistent with
      the low malignant potential of this lesion.

PMID- 14964543
TI  - Seatbelt injury causing perforation of the cervical esophagus: a case report and
      review of the literature.
AB  - Blunt trauma to the head and neck is a rare cause of cervical esophageal
      perforation. We report a cervical esophageal perforation caused by compression by
      a shoulder-harness seatbelt during a high-speed motor vehicle crash. We are not
      aware of a similar case in the trauma literature.

PMID- 14964544
TI  - Does setting specific goals and providing feedback during training result in
      better acquisition of laparoscopic skills?
AB  - The aim of this study was to evaluate whether setting specific goals and
      providing feedback stimulates trainees to improve their laparoscopic skills. Two
      groups of eight fourth-year medical students practiced on a MIST-VR trainer, a
      black box laparoscopic suturing trainer, and computer-based training modules for
      30 minutes, twice a week for 3 weeks. A precourse assessment of laparoscopic and
      open suturing skills and performance of MIST-VR tasks was obtained. Students in
      group A were given specific goals to achieve and were provided feedback. Group B
      was given no specific goals or feedback. At the end of the course, seven
      different tasks and skills were evaluated and subjectively scored during a
      laparoscopic cholecystectomy in an animal laboratory. A higher number of students
      in group A completed 10 or more repetitions in the MIST-VR than in group B. The
      groups showed no difference in final MIST-VR or overall scores in the animal
      laboratory. The only different scores between groups were for the use of the
      nondominant hand (NDH). The initial scores in the acquired cut task (ACT) in the
      MIST-VR correlated well with the performance in the animal laboratory. Setting
      goals and providing feedback tended to motivate students to practice more
      compared with the self-directed group. There was no difference in final MIST-VR
      scores or the performance in the animal laboratory, except for the NDH. The best
      predictor of performance was initial ACT score.

PMID- 14964545
TI  - Clinical studies of strangulating small bowel obstruction.
AB  - Reliable preoperative diagnosis of intestinal necrosis in strangulating small
      bowel obstruction (SSBO) is difficult, and, as yet, no reliable marker has been
      described. We, therefore, retrospectively examined clinical symptoms and
      hematobiochemical data of patients with SSBO in our surgical wards. Thirty-seven
      patients with SSBO were analyzed in this study. They were divided into two
      groups: group A (13 patients), the presence of gangrenous intestine; and group B
      (24 patients), the absence of it. By means of chi2 test, Student t test, or Welch
      t test, peritoneal signs, white blood cell count (leukocytosis or leukopenia),
      systemic inflammatory response syndrome (SIRS), shock, and base deficit were
      significantly associated with whether gangrenous intestine existed or not. Next,
      in simple regression analysis, base deficit was significantly correlated with the
      length of gangrenous intestine. In stepwise logistic regression analysis, SIRS
      was independently correlated with the presence of gangrenous intestine. If SIRS
      or metabolic acidosis is seen in patients with SSBO, the intestine is certainly
      gangrenous.

PMID- 14964546
TI  - The evolving management of blunt hepatic trauma in a rural setting.
AB  - Over the past decade, a nonoperative approach toward the management of blunt
      hepatic trauma has become prevalent at most major urban trauma centers. To
      determine the applicability of the nonoperative approach in a rural setting, a 10
      year retrospective review was conducted at a level I rural university-based
      trauma center. The Census Bureau defines ruralized areas to provide a better
      separation of urban and rural territory and population. A ruralized area is
      composed of one or more places and the adjacent surrounding territory that
      together have a maximum of 50,000 persons. West Virginia University is classified
      as a rural academic medical center and is situated in Morgantown, whose permanent
      population does not exceed 35,000. All patients with documented blunt hepatic
      trauma between July 1990 and June 2000 were identified and reviewed. To evaluate
      evolving trends, the patients were divided into two groups: group A (July 1, 1990
      June 30, 1995) and group B (July 1, 1995-June 30, 2000). There were 236 patients
      with documented blunt hepatic trauma identified between July 1, 1990, and June
      30, 2000). Overall, 70 per cent of patients were managed conservatively. When
      comparing the two groups, statistical significance was obtained in mean hospital
      length of stay (LOS) [19.8 days A vs. 9.1 days B (P < 0.0001)]; mean intensive
      care unit (ICU) days [15.2 days A vs. 5.3 days B (P < 0.0001)], blood transfusion
      [10 units A vs. 4.2 units B (P < 0.0016)], number of patients requiring surgery
      [52 (46%) A vs. 37 (30%) B (P < 0.022)]. There was only one death associated with
      nonoperative management. We have shown a definite trend toward nonoperative
      management of blunt hepatic trauma in a rural setting over the past decade. More
      than 70 per cent of our liver injury patients over the past 5 years have been
      managed nonoperatively, with statistically significant reductions in hospital
      LOS, ICU LOS, and transfusion requirements. We have found a definite trend over
      the past decade toward nonoperative management of blunt hepatic trauma in a rural
      setting. The rural setting with a delay in transport time to level I trauma
      center also did not significantly affect the outcome of the patients with
      nonoperative management of liver injuries. Approximately 78 per cent of our liver
      injury patients over the past 5 years have been managed nonoperatively and are
      associated with statistically significant reductions in hospital and ICU LOS and
      transfusion requirements.

PMID- 14964547
TI  - Mucosal regeneration of a duodenal defect using small intestine submucosa.
AB  - Intestinal tissue engineering has the potential of developing new treatment
      strategies for patients with a deficit in intestinal surface area. The purpose of
      this study was to investigate the capacity of small intestine submucosa (SIS) to
      regenerate intestinal epithelia in a rodent model for a duodenal defect. A
      duodenotomy was created in 20 Sprague-Dawley rats and was repaired with a
      circular patch of SIS. The repaired sites were retrieved 1, 2, 4, and 12 weeks
      after implantation. The size of the residual mucosal defect was measured. The
      retrieved tissues were fixed in formalin and processed by standard histologic
      techniques. The animals tolerated the procedure well. The mean size of the
      mucosal defects significantly decreased with time. Complete epithelialization of
      the defects was noted within 4 weeks in three of five samples. Histologically,
      the defects were lined with crypts and villi, but the muscularis layer did not
      regenerate. In the rodent model, SIS can be used as a patch to repair a
      duodenotomy. Mucosal regeneration was observed in the area of the defect. Further
      studies will determine whether SIS may be used to preserve or increase mucosal
      surface area in patients whose bowel length is compromised.

PMID- 14964548
TI  - Granular cell tumor of the breast.
AB  - Granular cell tumors (GCT) are uncommon, usually benign, neoplasms that are
      thought to derive from Schwann cells of the peripheral nerves. They can originate
      anywhere in the body but are most frequently found in the head and neck,
      particularly in the oral cavity. When they are located in the breast, as may
      occur in 5-8 per cent of cases, the clinical and pathologic appearance is similar
      to that of a malignant tumor. Immunohistochemical analysis, including reactivity
      for periodic acid-Schiff, CD68, and S100 and negative reactivity for cytokeratin,
      is required for definitive diagnosis. Awareness of this tumor's unique
      characteristics might aid in differentiating it from the more common malignant
      tumors of the breast.

PMID- 14964549
TI  - Intraductal oncocytic papillary neoplasm of the extrahepatic biliary tree: first
      report.
AB  - Tumors with oncocytic differentiation may occur in a variety of organs, but are
      extremely rare in the biliary system. Intraductal oncocytic papillary neoplasms
      (IOPNs) were first described in the pancreas to differentiate a rare subset of
      pancreatic neoplasm from the intraductal papillary mucinous neoplasms (IPMNs).
      IOPN of the extrahepatic biliary tree has not been previously described. We
      describe the first case of an intraductal oncocytic papillary neoplasm at the
      bifurcation of the common hepatic duct in a 52-year-old white male with a two
      year history of intermittent biliary obstruction.

PMID- 14964550
TI  - Role of sentinel lymph node biopsy in patients with thick (>4 mm) primary
      melanoma.
AB  - Lymphatic mapping and sentinel lymphadenectomy have become a routine part of the
      treatment algorithm for primary melanoma. Their role in the management of thick
      (>4 mm) lesions is evolving. Our purpose was to evaluate the influence of single
      lymph node (SLN) histology on survival of patients with thick melanomas. A
      computerized patient database was accessed to obtain records on patients with
      thick melanomas. Survival curves were constructed with the Kaplan-Meier method,
      and a Cox regression analysis was used to establish statistical significance.
      Between 1997 and 2002, 266 SLN biopsy procedures were performed, using both
      radioisotope and blue dye, in 259 patients with malignant melanoma. Forty-five
      patients (17%) had thick melanomas. Twenty patients (44%) had at least one
      positive sentinel lymph node. The mean disease-free survival (DFS) of SLN
      positive patients was 44 months compared with 53 months in SLN-negative patients
      (P = 0.0221). Increasing Breslow thickness was associated with a decrease in DFS,
      whereas no other histologic parameters such as Clark level, mitotic rate, or
      ulceration had an influence on DFS. Our data indicate that the status of the SLN
      node is predictive of disease-free survival in patients with thick melanomas. SLN
      biopsy is thus justified in patients with thick melanoma.

PMID- 14964551
TI  - Sweat gland carcinoma.
AB  - Sweat gland carcinoma is a rare malignant tumor of the skin adnexa that can occur
      in a variety of locations. It is a slow-growing tumor that metastasizes early and
      often. The rarity of this tumor has led to a relative lack of adequate evidence
      with regard to treating this entity. Recent advances in immunohistochemical
      staining have better defined this tumor and have aided in diagnosing its subtypes
      though histologic grade and presence of regional lymph nodes at the time of
      diagnosis. These are the best indicators for prognosis and management currently
      available. Indications for sentinel node biopsy are currently not well defined.
      Because of the poor prognosis of high-grade sweat gland carcinoma, clinicians
      should be aware of this entity and be prepared to treat aggressively. Management
      of sweat gland carcinoma is difficult because extensive study into both surgical
      and nonsurgical treatment has not been done. We present a case of sweat gland
      carcinoma of the lower extremity and a review of the clinicopathologic literature
      of these rare neoplasms, including diagnosis and surgical management.

PMID- 14964552
TI  - Antiperistaltic (retrograde) intussusception after Roux-en-Y gastric bypass.
AB  - Adult intussusception has been described after various types of gastrointestinal
      surgery. In some instances there may be intussusception of the jejunum into the
      stomach via a gastrointestinal stoma, a rare complication known as jejunogastric
      intussusception (JGI). We present a retrospective review of two cases of
      retrograde intussusception occurring years after open Roux-en-Y gastric bypass
      (RYGB) for morbid obesity. To our knowledge there have been no documented reports
      of JGI occurring after RYGB and only scattered reports of JGI after Roux-en-Y
      reconstruction in general. Two reports of intussusception following RYGB were
      identified in the English literature and comprised three patients, only one of
      whom suffered a retrograde intussusception. As the number of RYGB procedures
      continues to rise, we will likely see more of this entity; and it is therefore
      crucial that surgeons consider acute and chronic intussusception as a cause of
      abdominal pain in patients who have undergone RYGB.

PMID- 14964553
TI  - Splenic infarction associated with anti-cardiolipin antibody: a report of two
      cases.
AB  - There are few cases of splenic infarction associated with antiphospholipid
      antibody reported in the literature. We present two cases of splenic infarction
      associated with anticardiolipin antibody, one complicated by the development of a
      splenic pseudocyst. Clinical diagnostic features of splenic infarction are
      described. In addition, a review of the literature on thrombotic manifestations
      of antiphospholipid syndrome is presented.

PMID- 14964554
TI  - Independent predictors of morbidity and mortality in blunt colon trauma.
AB  - We sought to determine the impact of (1) grade of the colon injury, (2) the
      formation of an ostomy, and (3) associated injuries on outcomes such as morbidity
      and mortality after blunt colon injuries. We retrospectively reviewed 16,814
      cases of blunt abdominal trauma. Patients with colonic injuries were selected and
      charts reviewed for demographic, clinical, and outcomes data. Injuries were
      grouped by the Colon Injury Scale (grades I-V). Independent risk factors of
      morbidity included spine and lung injuries, as well as increased age. A higher
      grade of colon injury trended toward a significant association with intra
      abdominal complications. Independent risk factors of mortality included liver,
      heart, and lung injuries, as well as intracerebral blood and female gender. The
      grade of colon injury, the formation of an ostomy, and management of the colon
      trauma did not independently predict increased intra-abdominal complications,
      morbidity, or mortality. These results indicate that patients afflicted with
      blunt colon trauma experience a high rate of morbidity and mortality from
      associated injuries and or increased age. Treatment regimens directed at these
      factors will be most helpful in reducing the high morbidity and mortality after
      blunt colon trauma. Factors such as ostomy formation and management strategy are
      not associated with increased morbidity or mortality after blunt colon trauma.

PMID- 14964555
TI  - Usefulness of ultrasound scissors in reducing serous drainage after axillary
      dissection for breast cancer: a prospective randomized clinical study.
AB  - Axillary dissection is usually associated with prolonged serous drainage that may
      result in several complications. We analyzed whether the use of ultrasound
      scissors may decrease the total amount of drainage from the axilla (AD) in
      patients requiring curative surgery for breast cancer. Seventy-six women (median
      age, 56 years; range, 32-73 years) with confirmed pT1-3, N0-1 breast cancer were
      prospectively randomly assigned to undergo mastectomy or breast-conserving
      surgery with axillary dissection by either using (group A) or not using (group B)
      ultrasound scissors. Overall, there was a linear relationship (P < 0.05) between
      AD and both total number of the removed nodes and body mass index, whereas no
      correlation (P = NS) was found with age and size of the tumor. Total AD was
      higher (492 +/- 153 vs. 408 +/- 136 mL, P = 0.013) in group B, whereas the
      postoperative hospital stay was shorter (2.4 +/- 0.6 vs. 2.7 +/- 0.7 days, P =
      NS) in group A. The three-way analysis of covariance using the number of total
      removed nodes as covariate showed that lymph node status, type of operation, and
      technique for axillary dissection significantly (P < 0.05) correlated with AD. In
      conclusion, our initial study shows that the use of ultrasound scissors
      significantly reduced total AD in patients requiring axillary dissection and may
      shorten hospital stay.

PMID- 14964556
TI  - Duodenal switch procedure for benign duodenal disorders.
AB  - The duodenal switch operation has been found to be a very useful operation for a
      variety of nonbariatric procedures. A small series of patients operated on for
      primary bowel reflux, duodenal diverticula, and benign duodenal obstruction have
      all faired well. This procedure offers a much more physiologic approach to
      certain duodenal problems than a gastric jejunojejunostomy.

PMID- 14964557
TI  - Loop colostomy without a rod.
AB  - Loop colostomy is traditionally prevented from retracting into the peritoneal
      cavity by a rod or other supporting device. The rod can be safely replaced by a
      single suture. The technique facilitates fitting of the ostomy bag and eliminates
      the need to remove the supporting element later on.

PMID- 14964558
TI  - The language of modern medicine: it's all Greek to me.
AB  - The Greek language has shaped and formed the lexicon of modern medicine. Although
      medical terminology may seem complex and difficult to master, the clarity and
      functionality of this language owe a great debt to the tongue of the classical
      Greeks.

PMID- 14964559
TI  - Re: Management of traumatic abdominal wall hernia.

PMID- 14964560
TI  - Probabilistic independent component analysis for functional magnetic resonance
      imaging.
AB  - We present an integrated approach to probabilistic independent component analysis
      (ICA) for functional MRI (FMRI) data that allows for nonsquare mixing in the
      presence of Gaussian noise. In order to avoid overfitting, we employ objective
      estimation of the amount of Gaussian noise through Bayesian analysis of the true
      dimensionality of the data, i.e., the number of activation and non-Gaussian noise
      sources. This enables us to carry out probabilistic modeling and achieves an
      asymptotically unique decomposition of the data. It reduces problems of
      interpretation, as each final independent component is now much more likely to be
      due to only one physical or physiological process. We also describe other
      improvements to standard ICA, such as temporal prewhitening and variance
      normalization of timeseries, the latter being particularly useful in the context
      of dimensionality reduction when weak activation is present. We discuss the use
      of prior information about the spatiotemporal nature of the source processes, and
      an alternative-hypothesis testing approach for inference, using Gaussian mixture
      models. The performance of our approach is illustrated and evaluated on real and
      artificial FMRI data, and compared to the spatio-temporal accuracy of results
      obtained from classical ICA and GLM analyses.

PMID- 14964562
TI  - Noninvasive vascular elastography: theoretical framework.
AB  - Changes in vessel wall elasticity may be indicative of vessel pathologies. It is
      known, for example, that the presence of plaque stiffens the vascular wall, and
      that the heterogeneity of its composition may lead to plaque rupture and
      thrombosis. Another domain of application where ultrasound elastography may be of
      interest is the study of vascular wall elasticity to predict the risk of
      aneurysmal tissue rupture. In this paper, this technology is introduced as an
      approach to noninvasively characterize superficial arteries. In such a case, a
      linear array ultrasound transducer is applied on the skin over the region of
      interest, and the arterial tissue is dilated by the normal cardiac pulsation. The
      elastograms, the equivalent elasticity images, are computed from the assessment
      of the vascular tissue motion. Investigating the forward problem, it is shown
      that motion parameters might be difficult to interpret; that is because tissue
      motion occurs radially within the vessel wall while the ultrasound beam
      propagates axially. As a consequence of that, the elastograms are subjected to
      hardening and softening artefacts, which are to be counteracted. In this paper,
      the Von Mises (VM) coefficient is proposed as a new parameter to circumvent such
      mechanical artefacts and to appropriately characterize the vessel wall. Regarding
      the motion assessment, the Lagrangian estimator was used; that is because it
      provides the full two-dimensional strain tensor necessary to compute the VM
      coefficient. The theoretical model was validated with biomechanical simulations
      of the vascular wall properties. The results allow believing in the potential of
      the method to differentiate hard plaques and lipid pools from normal vascular
      tissue. Potential in vivo implementation of noninvasive vascular elastography to
      characterize abdominal aneurysms and superficial arteries such as the femoral and
      the carotid is discussed.

PMID- 14964561
TI  - Ultrasound elastography based on multiscale estimations of regularized
      displacement fields.
AB  - Elasticity imaging is based on the measurements of local tissue deformation. The
      approach to ultrasound elasticity imaging presented in this paper relies on the
      estimation of dense displacement fields by a coarse-to-fine minimization of an
      energy function that combines constraints of conservation of echo amplitude and
      displacement field continuity. The multiscale optimization scheme presents
      several characteristics aimed at improving and accelerating the convergence of
      the minimization process. This includes the nonregularized initialization at the
      coarsest resolution and the use of adaptive configuration spaces. Parameters of
      the energy model and optimization were adjusted using data obtained from a tissue
      like phantom material. Elasticity images from normal in vivo breast tissue were
      subsequently obtained with these parameters. Introducing a smoothness constraint
      into motion field estimation helped solve ambiguities due to incoherent motion,
      leading to elastograms less degraded by decorrelation noise than the ones
      obtained from correlation-based techniques.

PMID- 14964563
TI  - Visual and quantitative evaluation of selected image combination schemes in
      ultrasound spatial compound scanning.
AB  - Multi-angle spatial compound images are normally generated by averaging the
      recorded single-angle images (SAIs). To exploit possible advantages associated
      with alternative combination schemes, this paper investigates both the effect of
      number of angles (Ntheta) as well as operator (mean, median, mean-excluding
      maximum (mem), root-mean-square (rms), geometric mean and maximum) on image
      quality (tissue delineation and artifacts), speckle signal-to-noise ratio (SNRs)
      and contrast. The evaluation is based on in vitro SAI (+/-21 degrees in steps of
      delta theta = 7 degrees) of formalin fixed porcine tissue containing adipose,
      connective and muscular tissue. Image quality increased with number of angles up
      to +/-14 degrees after which the improvements became debatable. The mem and
      median operators, which try to render the images more quantitatively correct by
      suppressing strong echoes from specular reflectors, provide some improvement in
      this regard. When combining the SAI with the mean operator, the SNR, increases-
      in general--with Ntheta. For Ntheta = 2, the SNRs increases with delta theta as
      expected. When Ntheta = 7, the highest SNRs is obtained for the mem, rms, and
      geometric mean operators, while the lowest SNRs is obtained for the maximum
      operator. When comparing SNRs for adipose and fibrous tissue, the level is close
      to 1.91 for adipose tissue but only 1.7 for fibrous tissue which contain
      relatively few organized scattering structures.

PMID- 14964564
TI  - An adaptive level set segmentation on a triangulated mesh.
AB  - Level set methods offer highly robust and accurate methods for detecting
      interfaces of complex structures. Efficient techniques are required to transform
      an interface to a globally defined level set function. In this paper, a novel
      level set method based on an adaptive triangular mesh is proposed for
      segmentation of medical images. Special attention is paid to an adaptive mesh
      refinement and redistancing technique for level set propagation, in order to
      achieve higher resolution at the interface with minimum expense. First, a narrow
      band around the interface is built in an upwind fashion. An active square
      technique is used to determine the shortest distance correspondence (SDC) for
      each grid vertex. Simultaneously, we also give an efficient approach for signing
      the distance field. Then, an adaptive improvement algorithm is proposed, which
      essentially combines two basic techniques: a long-edge-based vertex insertion
      strategy, and a local improvement. These guarantee that the refined triangulation
      is related to features along the front and has elements with appropriate size and
      shape, which fit the front well. We propose a short-edge elimination scheme to
      coarsen the refined triangular mesh, in order to reduce the extra storage.
      Finally, we reformulate the general evolution equation by updating 1) the
      velocities and 2) the gradient of level sets on the triangulated mesh. We give an
      approach for tracing contours from the level set on the triangulated mesh. Given
      a two-dimensional image with N grids along a side, the proposed algorithms run in
      O(kN) time at each iteration. Quantitative analysis shows that our algorithm is
      of first order accuracy; and when the interface-fitted property is involved in
      the mesh refinement, both the convergence speed and numerical accuracy are
      greatly improved. We also analyze the effect of redistancing frequency upon
      convergence speed and accuracy. Numerical examples include the extraction of
      inner and outer surfaces of the cerebral cortex from magnetic resonance imaging
      brain images.

PMID- 14964565
TI  - Tomographic image reconstruction based on a content-adaptive mesh model.
AB  - In this paper, we explore the use of a content-adaptive mesh model (CAMM) for
      tomographic image reconstruction. In the proposed framework, the image to be
      reconstructed is first represented by a mesh model, an efficient image
      description based on nonuniform sampling. In the CAMM, image samples (represented
      as mesh nodes) are placed most densely in image regions having fine detail.
      Tomographic image reconstruction in the mesh domain is performed by maximum
      likelihood (ML) or maximum a posteriori (MAP) estimation of the nodal values from
      the measured data. A CAMM greatly reduces the number of unknown parameters to be
      determined, leading to improved image quality and reduced computation time. We
      demonstrated the method in our experiments using simulated gated single photon
      emission computed tomography (SPECT) cardiac-perfusion images. A channelized
      Hotelling observer (CHO) was used to evaluate the detectability of perfusion
      defects in the reconstructed images, a task-based measure of image quality. A
      minimum description length (MDL) criterion was also used to evaluate the effect
      of the representation size. In our application, both MDL and CHO suggested that
      the optimal number of mesh nodes is roughly five to seven times smaller than the
      number of projection bins. When compared to several commonly used methods for
      image reconstruction, the proposed approach achieved the best performance, in
      terms of defect detection and computation time. The research described in this
      paper establishes a foundation for future development of a (four-dimensional)
      space-time reconstruction framework for image sequences in which a built-in
      deformable mesh model is used to track the image motion.

PMID- 14964566
TI  - Fully Bayesian spatio-temporal modeling of FMRI data.
AB  - We present a fully Bayesian approach to modeling in functional magnetic resonance
      imaging (FMRI), incorporating spatio-temporal noise modeling and haemodynamic
      response function (HRF) modeling. A fully Bayesian approach allows for the
      uncertainties in the noise and signal modeling to be incorporated together to
      provide full posterior distributions of the HRF parameters. The noise modeling is
      achieved via a nonseparable space-time vector autoregressive process. Previous
      FMRI noise models have either been purely temporal, separable or modeling
      deterministic trends. The specific form of the noise process is determined using
      model selection techniques. Notably, this results in the need for a spatially
      nonstationary and temporally stationary spatial component. Within the same full
      model, we also investigate the variation of the HRF in different areas of the
      activation, and for different experimental stimuli. We propose a novel HRF model
      made up of half-cosines, which allows distinct combinations of parameters to
      represent characteristics of interest. In addition, to adaptively avoid over
      fitting we propose the use of automatic relevance determination priors to force
      certain parameters in the model to zero with high precision if there is no
      evidence to support them in the data. We apply the model to three datasets and
      observe matter-type dependence of the spatial and temporal noise, and a negative
      correlation between activation height and HRF time to main peak (although we
      suggest that this apparent correlation may be due to a number of different
      effects).

PMID- 14964567
TI  - Automatic identification of the pectoral muscle in mammograms.
AB  - The pectoral muscle represents a predominant density region in most medio-lateral
      oblique (MLO) views of mammograms; its inclusion can affect the results of
      intensity-based image processing methods or bias procedures in the detection of
      breast cancer. Local analysis of the pectoral muscle may be used to identify the
      presence of abnormal axillary lymph nodes, which may be the only manifestation of
      occult breast carcinoma. We propose a new method for the identification of the
      pectoral muscle in MLO mammograms based upon a multiresolution technique using
      Gabor wavelets. This new method overcomes the limitation of the straight-line
      representation considered in our initial investigation using the Hough transform.
      The method starts by convolving a group of Gabor filters, specially designed for
      enhancing the pectoral muscle edge, with the region of interest containing the
      pectoral muscle. After computing the magnitude and phase images using a vector
      summation procedure, the magnitude value of each pixel is propagated in the
      direction of the phase. The resulting image is then used to detect the relevant
      edges. Finally, a post-processing stage is used to find the true pectoral muscle
      edge. The method was applied to 84 MLO mammograms from the Mini-MIAS
      (Mammographic Image Analysis Society, London, U.K.) database. Evaluation of the
      pectoral muscle edge detected in the mammograms was performed based upon the
      percentage of false-positive (FP) and false-negative (FN) pixels determined by
      comparison between the numbers of pixels enclosed in the regions delimited by the
      edges identified by a radiologist and by the proposed method. The average FP and
      FN rates were, respectively, 0.58% and 5.77%. Furthermore, the results of the
      Gabor-filter-based method indicated low Hausdorff distances with respect to the
      hand-drawn pectoral muscle edges, with the mean and standard deviation being 3.84
      +/- 1.73 mm over 84 images.

PMID- 14964568
TI  - An object-based approach for detecting small brain lesions: application to
      Virchow-Robin spaces.
AB  - This paper is concerned with the detection of multiple small brain lesions from
      magnetic resonance imaging (MRI) data. A model based on the marked point process
      framework is designed to detect Virchow-Robin spaces (VRSs). These tubular shaped
      spaces are due to retraction of the brain parenchyma from its supplying arteries.
      VRS are described by simple geometrical objects that are introduced as small
      tubular structures. Their radiometric properties are embedded in a data term. A
      prior model includes interactions describing the clustering property of VRS. A
      Reversible Jump Markov Chain Monte Carlo algorithm (RJMCMC) optimizes the
      proposed model, obtained by multiplying the prior and the data model. Example
      results are shown on T1-weighted MRI datasets of elderly subjects.

PMID- 14964569
TI  - Optic nerve head segmentation.
AB  - Reliable and efficient optic disk localization and segmentation are important
      tasks in automated retinal screening. General-purpose edge detection algorithms
      often fail to segment the optic disk due to fuzzy boundaries, inconsistent image
      contrast or missing edge features. This paper presents an algorithm for the
      localization and segmentation of the optic nerve head boundary in low-resolution
      images (about 20 microns/pixel). Optic disk localization is achieved using
      specialized template matching, and segmentation by a deformable contour model.
      The latter uses a global elliptical model and a local deformable model with
      variable edge-strength dependent stiffness. The algorithm is evaluated against a
      randomly selected database of 100 images from a diabetic screening programme. Ten
      images were classified as unusable; the others were of variable quality. The
      localization algorithm succeeded on all bar one usable image; the contour
      estimation algorithm was qualitatively assessed by an ophthalmologist as having
      Excellent-Fair performance in 83% of cases, and performs well even on blurred
      images.

PMID- 14964570
TI  - Various clinical types of Q-fever disease.

PMID- 14964571
TI  - Cibenzoline therapy for mitral regurgitation in patients with HOCM.

PMID- 14964572
TI  - How to diagnose and treat a licorice-induced syndrome with findings similar to
      that of primary hyperaldosteronism.

PMID- 14964573
TI  - Ever-changing concepts of calciphylaxis.

PMID- 14964574
TI  - Mechanisms of tubulointerstitial injury in the kidney: final common pathways to
      end-stage renal failure.
AB  - There are many different glomerular disorders, including glomerulonephritis,
      diabetic nephropathy, and hypertensive nephrosclerosis. However, once glomerular
      damage reaches a certain threshold, the progression of renal disease is
      consistent and irreversible. Recent studies emphasized the crucial role of
      tubulointerstitial injury as a mediator of progression of kidney disease. One
      common mechanism that leads to renal failure via tubulointerstitial injury is
      massive proteinuria. Accumulating evidence suggests critical effects of filtered
      macromolecules on tubular cells, including lysosomal rupture, energy depletion,
      and tubular injury directly induced by specific components such as complement
      components. Another common mechanism is chronic hypoxia in the
      tubulointerstitium. Tubulointerstitial damage results in the loss of peritubular
      capillaries, impairing blood flow delivery. Interstitial fibrosis also impairs
      oxygen diffusion and supply to tubular cells. This induces chronic hypoxia in
      this compartment, rendering a vicious cycle. Development of novel therapeutic
      approaches against these final common pathways will enable us to target any types
      of renal disease.

PMID- 14964575
TI  - A guideline for the treatment of dementia in Japan.
AB  - Worldwide energetic efforts have provided several clues for the management of
      Alzheimer's disease and related dementias in elderly people, although the history
      of dementia treatment is not long. Various pharmacological or non-pharmacological
      treatments are carried out in daily medical practice, but evidence for the
      validity of these treatments is limited. In United States and Europe, several
      pharmacological and a few non-pharmacological treatments have been proven
      effective and a few drugs are approved by various governments and used in
      practice. In contrast, only one acetylcholinesterase inhibitor, donepezil has
      been proven effective and used for patients with mild or moderate Alzheimer's
      disease in Japan. Anti-hypertensive or anti-platelet therapy has been shown to
      reduce the incidence or recurrence of stroke, probably preventing vascular
      dementia. Effectiveness of drugs and types of care awaits to be validated in the
      light of scientific procedures.

PMID- 14964576
TI  - Nephrotic syndrome caused by membranous nephropathy: response to a short course
      of cyclophosphamide alternating with prednisolone.
AB  - OBJECTIVE: The optimal duration of immunosuppressive therapy and the timing of
      treatment for treating membranous nephropathy (MN) have yet to be established. We
      examined outcomes of a short course of cyclophosphamide alternating with
      prednisolone for MN patients with nephrotic syndrome. METHODS AND PATIENTS:
      Cyclophosphamide (2 mg/kg/day for 8 weeks) combined with prednisolone (1 mg/kg
      every 48 hours for 8 weeks, then tapering off for 1 year) was prescribed for 28
      MN patients (12 men and 16 women; mean age 52.4+/-2.25 years SEM). We first
      evaluated the response rates to this combined therapy, then compared the clinical
      characteristics of those who achieved remission (group A) with those who did not
      (group B) within 6 months of the start of treatment. RESULTS: The incidences of
      complete and partial remission increased with the follow-up period; 32 and 21% by
      6 months, 54 and 29% by 12 months, and 79 and 11% by 24 months, respectively.
      Serum IgG (906+/-100.8 versus 562+/-66.1 mg/day; p<0.01) was significantly higher
      in group A, and the selectivity index (C(IgG)/C(albumin) 0.16+/-0.015 versus
      0.30+/-0.040; p<0.01), significantly lower. Nephrotic syndrome persisted in 3
      group B patients (23%), who finally had impaired renal function. CONCLUSION: MN
      patients with nephrotic syndrome responded favorably to a short course of
      cyclophosphamide combined with prednisolone. The serum IgG level and selectivity
      index may serve as markers of early response to this treatment.

PMID- 14964577
TI  - Development and psychometric analysis of the Japanese version of the Nottingham
      Health Profile: cross-cultural adaptation.
AB  - OBJECTIVE: To adapt the Nottingham Health Profile (NHP) for Japanese and to
      describe the results of the assessment of its psychometric properties. METHODS:
      Assessments included test-retest reliability over approximately a 2-week
      interval, internal consistency and construct validity in 133 patients with COPD.
      RESULTS: The distribution of scores indicated that most of the NHP sections
      exhibited a floor effect, although this is greatly reduced with the NHP-Distress
      scale. The test-retest reliability was above 0.8 for all sections when patients
      reporting any change in their health status rating were excluded. Cronbach's
      alpha coefficients reflected the number of items contained in each section. The
      internal consistency of the emotional reactions section at one timepoint and the
      physical mobility section at both timepoints were lower than expected to be
      higher. All sections except the pain section could be used to distinguish
      patients who reported their health status to be good or fair from those who rated
      it to be poor or very poor. CONCLUSION: The adaptation of the NHP for Japanese
      was successful. Most sections showed reasonable test-retest reliability,
      indicating that they produced acceptable levels of random measurement error. The
      internal consistency of the sections was confirmed, although the alpha values of
      the emotional reactions and physical mobility sections were lower than might be
      expected for scales of their length. Different sections of the Japanese NHP were
      shown to have known group validity.

PMID- 14964578
TI  - Non-herpetic acute limbic encephalitis: cerebrospinal fluid cytokines and
      magnetic resonance imaging findings.
AB  - OBJECTIVE: Non-herpetic acute limbic encephalitis (non-herpetic ALE) is regarded
      as a new subgroup of limbic encephalitis. In the present study, clinical findings
      and cerebrospinal fluid (CSF) cytokines in patients with non-herpetic ALE were
      investigated. PATIENTS AND METHODS: For adult inpatients in our hospital and
      related hospitals from 1996 to 2001, non-herpetic ALE was examined according to
      the criteria described in this study. Six patients were diagnosed as having non
      herpetic ALE, and their clinical data and magnetic resonance imaging (MRI) were
      analyzed. In the CSF samples of the 6 patients with non-herpetic ALE and 6
      patients with herpes simplex encephalitis (HSE), the concentrations of tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and interferon (IFN)
      gamma were determined using sandwich-type enzyme-linked immunosorbent assay
      (ELISA) kits. RESULTS: The six patients with non-herpetic ALE showed all the
      acute encephalitis features, such as fever, altered consciousness, seizures,
      memory impairment, and mild CSF pleocytosis. MRI demonstrated selective abnormal
      signals in the limbic system, including the bilateral hippocampi and amygdalae.
      The levels of CSF IL-6 and IFN-gamma in patients with non-herpetic ALE were
      significantly lower than those in patients with HSE (p<0.05 and p<0.01,
      respectively). The levels of both TNF-alpha and IL-1beta were below the detection
      limits in both groups. CONCLUSION: Six patients were newly diagnosed as having
      non-herpetic ALE in this study. These patients revealed both acute limbic
      encephalitis and MRI abnormalities in the bilateral hippocampi and amygdalae. The
      levels of IL-6 and IFN-gamma in the CSF of patients with non-herpetic ALE were
      significantly lower than those of patients with HSE, possibly reflecting an
      immunological process in this type of ALE rather than direct viral infection.

PMID- 14964579
TI  - Improvement of chronic nonspecific symptoms by long-term minocycline treatment in
      Japanese patients with Coxiella burnetii infection considered to have post-Q
      fever fatigue syndrome.
AB  - OBJECTIVE: To address the presence of post-Q fever fatigue syndrome (post-QFS) in
      Japan, and to evaluate the efficacy of minocycline for this condition. PATIENTS
      AND METHODS: In 20 Coxiella burnetii (C. burnetii) seropositive patients with
      persistent nonspecific symptoms including general fatigue, low-grade fever,
      myalgia and arthralgia, changes in subjective symptoms, C. burnetii antibody
      titers and C. burnetii DNA were evaluated after antibiotic treatment. RESULTS:
      After treatment mainly with minocycline (100 mg/day for 3 months), the clinical
      picture improved in all 20 patients as evidenced by decreases in body temperature
      (13/17), general fatigue (20/20) and headache (9/12). The mean performance status
      (PS) score improved from 5.0 to 1.8 (p<0.01). All 7 who had been positive for C.
      burnetii DNA, became negative together with an improvement in subjective
      symptoms. Indirect immunofluorescence tests demonstrated 6 of the 20 patients to
      be positive for C. burnetii IgM antibody to phase II antigen (1:32), and 18 to be
      positive for IgG antibody (1:128, 1:256). Antibody titers of both IgM (6/6, 1:16)
      and IgG (18/18, 1:16) decreased markedly after treatment. CONCLUSION: These
      results of an open label study in Japan suggest that minocycline administration
      is useful for improving chronic nonspecific symptoms considered to be post-Q
      fever fatigue syndrome caused by C. burnetii infection.

PMID- 14964580
TI  - Mitral regurgitation disappearance after cibenzoline treatment in a patient with
      hypertrophic obstructive cardiomyopathy.
AB  - Hypertrophic obstructive cardiomyopathy (HOCM), which shows left ventricular
      outflow pressure gradient (LVPG), is often complicated with mitral regurgitation
      (MR). We examined a 62-year-old Japanese female with HOCM and MR. Ultrasound
      echocardiography showed severe MR, asymmetrical septal hypertrophy, systolic
      anterior movement of the mitral valve anterior leaflet, and left ventricular
      outflow stenosis. Her LVPG, measured using continuous wave Doppler recording, was
      118 mmHg. During heart catheterization, the aortic pressure and left ventricular
      pressure were simultaneously measured. An intravenous injection of 70 mg
      cibenzoline decreased the LVPG from 110 mmHg to 16 mmHg. Left ventriculography
      was performed immediately after the injection and did not show MR. This clearly
      demonstrates that cibenzoline decreases LVPG in patients with HOCM and also
      improves the MR that arises from LVPG.

PMID- 14964581
TI  - Myoclonus and metabolic alkalosis from licorice in antacid.
AB  - A 90-year-old woman with hypertension developed metabolic alkalosis and
      myoclonus. Her medications included diltiazem hydrochloride, benidipine
      hydrochloride, kallidinogenase, procaterol hydrochloride, sennoside,
      dihydrocodeine phosphate, and KM powder antacid that contained 354 mg of licorice
      and 900 mg of sodium bicarbonate per 3.9 g of powder. Endocrinological studies
      showed slightly reduced plasma renin activity and normal plasma aldosterone
      concentration. A provisional diagnosis of licorice-induced metabolic alkalosis
      was established and the patient was successfully treated after correction of
      serum pH and cessation of the medications. Licorice-induced metabolic alkalosis
      must be considered in the differential diagnosis of myoclonus.

PMID- 14964582
TI  - Development of proximal calciphylaxis with penile involvement after
      parathyroidectomy in a patient on hemodialysis.
AB  - Elevated parathyroid hormone (PTH) levels and hyperphosphatemia are thought to be
      associated with the development of calciphylaxis. We report a patient on
      hemodialysis who developed proximal calciphylaxis with consistently low PTH
      levels after parathyroidectomy. A 31-year-old man was admitted to our hospital
      because of abdominal skin ulcerations. Calciphylaxis spread to the penis, and
      simultaneous progressive lung calcification was evident on chest X-ray,
      suggestive of pulmonary calciphylaxis on 99mTc-methylene disphosphonate
      scintigraphy. The patient died of respiratory failure despite intensive treatment
      including hyperbaric oxygen therapy. This is the first report of a patient on
      hemodialysis who developed calciphylaxis involving the penis after
      parathyroidectomy.

PMID- 14964583
TI  - Pulmonary hyalinizing granuloma with laryngeal and subcutaneous involvement:
      report of a case successfully treated with glucocorticoids.
AB  - We report a case of pulmonary hyalinizing granuloma (PHG) with laryngeal and
      subcutaneous involvement. A 43-year-old man was admitted to our hospital for
      assessment of hoarseness. Cervical and chest computed tomography, respectively,
      revealed a laryngeal tumor and two pulmonary masses. Specimens obtained from the
      pulmonary masses were compatible with PHG. The histopathology of biopsy specimens
      from both the laryngeal tumor and a subcutaneous tumor resembled that of the
      resected lung masses. Although there is no established treatment for PHG, the
      laryngeal tumor was diminished and all other lesions disappeared with
      glucocorticoid treatment.

PMID- 14964584
TI  - Acute promyelocytic leukemia with drug-induced hypersensitivity syndrome
      associated with Epstein-Barr virus infection.
AB  - We report a case of acute promyelocytic leukemia (APL) with drug-induced
      hypersensitivity syndrome associated with Epstein-Barr virus (EBV) infection. A
      33-year-old woman was admitted because of APL. After complete remission was
      obtained with the use of all-trans retinoic acid (ATRA), intensive chemotherapy
      was administered. She developed high grade fever and severe systemic erythematous
      eruptions followed by cervical lymphoadenopathy, hepatosplenomegaly, hepatitis
      and hypotension in a state of myelosuppression during consolidation chemotherapy.
      Systemic corticosteroids alleviated the symptoms. Since an anti-EB VCA IgM
      antibody titer was continuously positive, persistent infection of EBV was
      suspected. In this case, EBV infection may have contributed to the development of
      drug-induced hypersensitivity syndrome.

PMID- 14964585
TI  - Advanced Hirayama disease with successful improvement of activities of daily
      living by operative reconstruction.
AB  - Juvenile muscular atrophy of the distal upper extremity (Hirayama disease) is a
      benign and non-progressive motor neuron disease. Application of a cervical collar
      is believed to prevent progression of symptoms in the early stages, but there is
      no effective therapy for the advanced disease. We found that tendon transfer
      improved the activities of daily living (ADL) of a patient with advanced Hirayama
      disease. An operative reconstruction can be valuable, even in patients with
      Hirayama disease who have developed impaired ADL due to extensive intrinsic hand
      muscle atrophy.

PMID- 14964586
TI  - Effects of specific exercise instructions on abdominal muscle activity during
      trunk curl exercises.
AB  - STUDY DESIGN: A repeated-measures, counterbalanced design. OBJECTIVES: To test
      whether subjects could learn and retain the ability to alter the relative
      activity of abdominal muscle groups when performing trunk curl exercises.
      BACKGROUND: Although trunk curl exercises are widely prescribed, a disadvantage
      of trunk curls is that they primarily activate rectus abdominis, while the
      internal and external oblique abdominis muscles are considered to be more
      important contributors to lumbar stability. METHODS AND MEASURES: A convenience
      sample of 25 subjects performed trunk curl exercises in accordance with 3
      different sets of instructions: nonspecific instructions (NS), instructions
      intended to emphasize rectus abdominis activity (RE), and instructions intended
      to emphasize oblique abdominis activity (OE). Electromyographic (EMG) activity
      was recorded from the upper and lower rectus and the internal and external
      oblique abdominis muscles while a physical target was used to insure that the
      trunk was raised to the same height for all conditions. Normalized root-mean
      square EMG amplitude measures were used to test for instruction-dependent changes
      in the relative EMG activity of the rectus and oblique muscle groups. RESULTS:
      Following a single, brief, instruction session, subjects performing trunk curls
      had significantly greater normalized oblique:rectus EMG ratios when following OE
      instructions (mean [+/- SD] oblique-rectus ratio, 1.45 +/- 0.34) than when
      following RE (mean [+/- SD] oblique-rectus ratio, 0.76 +/- 0.24) or NS (mean
      [ISD] oblique-rectus ratio, 0.63 +/- 0.23) instructions. Retesting 1 week later
      indicated that subjects retained this skill. CONCLUSIONS: With minimal
      instruction, subjects are able to volitionally alter the relative activity of the
      oblique and rectus abdominis muscles when performing trunk curls. Incorporating
      instructions emphasizing oblique abdominis activity into lumbar stabilization
      programs appears promising and has potential advantages over other approaches to
      altering abdominal muscle activity during trunk

PMID- 14964587
TI  - Shortwave diathermy and prolonged stretching increase hamstring flexibility more
      than prolonged stretching alone.
AB  - STUDY DESIGN: A randomized, counterbalanced 2x3x5 repeated-measures design.
      OBJECTIVE: To compare changes in hamstring flexibility after treatments of pulsed
      shortwave diathermy and prolonged stretch, sham diathermy and prolonged stretch,
      and control. BACKGROUND: Heat and stretch techniques have been touted for years.
      To date, the effect of shortwave diathermy and hamstring stretching has not been
      studied. Because diathermy heats a large area and penetrates deep into the
      muscle, use of this device prior to or during hamstring stretching may increase
      flexibility. METHODS AND MEASURES: Thirty college-age students (mean age, 21.5
      years) with tight hamstrings (inability to achieve greater than 160 degrees knee
      extension at 90 degrees hip flexion) participated. Subjects were assigned to 1 of
      3 groups: diathermy and stretch, sham diathermy and stretch, and control). Range
      of motion was recorded before and after each treatment for 5 days and on day 8. A
      straight leg-raise stretch was performed using a mechanical apparatus. Subjects
      in the diathermy-and-stretch group received 10 minutes of diathermy (distal
      hamstrings) followed by 5 minutes of simultaneous diathermy and stretch, followed
      by 5 minutes of stretching only. Subjects in the sham-diathermy-and-stretch group
      followed the same protocol, but with the diathermy unit turned off. Subjects in
      the control group lay on the table for 20 minutes. Data were analyzed using an
      ANOVA and post hoc t tests. RESULTS: Mean (+/- pooled SE) increases in knee
      extension after 5 days were 15.8 degrees 2.2 degrees for the diathermy-and
      stretch group, 5.2 degrees +/- 2.2 degrees for the sham-diathermy-and-stretch
      group, and -0.3 degrees +/- 2.2 degrees for the control group. Seventy-two hours
      after the last treatment, the diathermy-and-stretch group lost 1.9 degrees +/-
      2.2 degrees, the sham-diathermy-and-stretch group lost 3.0 degrees +/- 2.2
      degrees, and the control group changed -0.4 degrees +/- 2.2 degrees. CONCLUSION:
      These results suggest that hamstring flexibility can be greatly improved when
      shortwave diathermy is used in conjunction with prolonged stretching.

PMID- 14964588
TI  - Neuromuscular electrical stimulation for quadriceps muscle strengthening after
      bilateral total knee arthroplasty: a case series.
AB  - STUDY DESIGN: A case series. OBJECTIVES: The purpose of this case series was to
      assess the effect of high-intensity neuromuscular electrical stimulation (NMES)
      on quadriceps strength and voluntary activation following total knee arthroplasty
      (TKA). BACKGROUND: Following TKA, patients exhibit long-term weakness of the
      quadriceps and diminished functional capacity compared to age-matched healthy
      controls. The pain and swelling that results from surgery may contribute to
      quadriceps weakness. The use of high-intensity NMES has previously been shown to
      be effective in quickly restoring quadriceps strength in patients with weakness
      after surgery. METHODS AND MEASURES: All patients were treated for 6 weeks, 2 to
      3 visits per week, in outpatient rehabilitation. Five patients (NMES group)
      participated in a voluntary exercise program for both knees and NMES for the
      weaker knee. Three patients (exercise group) participated in a voluntary exercise
      program for both knees without NMES. For each treatment session, 10 isometric
      electrically elicited muscle contractions were administered at maximally
      tolerated doses to the initially weaker leg of the NMES group. Quadriceps
      strength and muscle activation were repeatedly assessed up to 6 months after
      surgery using burst superimposition techniques. RESULTS: At 6 months, the weak
      NMES-treated legs of 4 of 5 patients in the NMES group had surpassed the strength
      of the contralateral leg. In contrast, none of the weak legs in the exercise
      group were stronger than the contralateral leg at 6 months. Changes in quadriceps
      muscle activation mirrored the changes exhibited in strength. CONCLUSION: When
      NMES was added to a voluntary exercise program, deficits in quadriceps muscle
      strength and activation resolved quickly after TKA.

PMID- 14964589
TI  - Seeding violence in the minds of children.

PMID- 14964590
TI  - Snake oil, ethics, and the first amendment: what's a profession to do?
AB  - This article considers the appropriate legal and ethical response to those whose
      advocacy of "alternative" or unvalidated therapies places people at risk of harm.
      What are our professional responsibilities with respect to such advocacy, and
      what sorts of harm will justify government intervention?

PMID- 14964591
TI  - Trauma in war and political persecution: expanding the concept.
AB  - A contextual understanding of the concept of trauma is proposed through a study
      of its meaning in a Latin American context facing war and political repression.
      This article explores the contributions of narrative and liberation psychology to
      understanding politically based trauma. It critiques the relationship between the
      concept of trauma and the diagnosis of posttraumatic stress disorder. It analyzes
      how Colombian human rights activists make sense of the political persecution and
      trauma in their work. The author argues that the kind of experiences that these
      activists have endured go beyond the category of stress and can best be
      understood as traumatic within the context of the current medium-intensity war in
      Colombia.

PMID- 14964592
TI  - Interpretations of the past and expectations for the future among Israeli and
      Palestinian youth.
AB  - This study was developed by a group of Israeli and Palestinian researchers for
      the purpose of examining social knowledge of young people in the conflicted
      region of the Middle East. The article examines the relations between measures of
      interpretations of the past (perceptions of legitimacy and emotional reactions
      toward the historical "narratives" of Israelis and Palestinians) and measures of
      expectations of the collective future, as reflected in conflict resolution
      beliefs. Data were collected from December 1999 to February 2000 (before the
      present crisis [2000-2002] in Jewish-Palestinian relations) among representative
      samples of high school students (Grades 10 and 12): 1,183 Palestinians in the
      Palestinian National Territories and 1,188 Israeli Jewish students. The results
      are discussed from developmental, social, and cultural perspectives.

PMID- 14964593
TI  - Role of kin and nonkin support in the mental health of low-income women.
AB  - Data from the Worcester Family Research Project were analyzed to determine
      whether social support processes are altered by poverty and whether kin and
      nonkin support are differentially related to mental health in low-income mothers.
      The authors found that conflict with family and friends predicted adverse mental
      health and more strongly predicted these outcomes than emotional and instrumental
      support. Moreover, sibling conflict was a stronger predictor of mental health
      than parent conflict. Finally, only instrumental support from professionals
      predicted mental health.

PMID- 14964594
TI  - Toward uncovering robust principles of change inherent to cognitive-behavioral
      therapy for psychosis.
AB  - Cognitive-behavioral therapies for people with schizophrenia have added value to
      the existing treatment of psychotic symptoms. This article aims at taking a
      closer look at the research results of multiple studies in order to delineate the
      specific and nonspecific factors related to the cognitive-behavioral practice
      that influence treatment robustness.

PMID- 14964595
TI  - Single- and dual-trauma couples: clinical observations of relational
      characteristics and dynamics.
AB  - Trauma survivors and their spouses/partners who seek therapy often present with
      unique dynamics owing to the ongoing effects of previous trauma. This article
      provides a clinical framework for understanding single-trauma (only 1 partner
      reports a trauma history) and dual-trauma (both partners report a trauma history)
      couples. The descriptions of single- and dual-trauma couples were developed
      through several focus group discussions. Interpersonal patterns characteristic of
      single- and dual-trauma couples are described. We emphasize the importance of
      using a "trauma lens" when working with couples and families to avoid overlooking
      important cues about the individual and systemic effects of traumatic stress.

PMID- 14964596
TI  - Compromised emotional competence: seeds of violence sown early?
AB  - The authors expected less secure preschoolers to be less emotionally competent
      when interacting with peers at age 3 and that these emotionally incompetent
      children, especially those who showed much unregulated anger, would be less
      socially competent in kindergarten. These directional hypotheses were examined in
      a sample of 91 preschoolers, and all were corroborated.

PMID- 14964597
TI  - Attention and conduct problems in children exposed to family violence.
AB  - This study examines the impact of family violence on the development of attention
      and conduct problems in girls and boys. Mothers (n = 287) were interviewed and
      given diagnostic assessment instruments to measure attention
      deficit/hyperactivity disorder and conduct disorder in 1 of their children. Six
      years later, youths were interviewed about their delinquent behavior. Family
      violence related to attention and conduct problems in girls only. Girls who
      displayed these problems in childhood were not necessarily at risk for later
      delinquency. Family violence in childhood had a direct effect on delinquency in
      girls. Boys who developed attention problems were more likely to show conduct
      problems that eventually led to adolescent delinquency. Family violence failed to
      account for problems or delinquency in boys.

PMID- 14964598
TI  - Normalization of violence among inner-city youth: a formulation for research.
AB  - A causal model is formulated for the thesis that in inner-city youth exposed to
      high levels of violence, cognitions that normalize violence mitigate affective
      effects of exposure while increasing risk for violent behavior, thus perpetuating
      violence in the very process of adapting to it psychologically. Gender
      differences in the cognitive normalization of violence may explain gender
      differences in affective and behavioral effects of exposure. Empirical studies
      are needed to directly test this model.

PMID- 14964599
TI  - Negative coping as mediator in the relation between violence and outcomes: inner
      city African American youth.
AB  - The present study examined whether negative coping mediated the relation between
      exposure to violence and psychological outcomes (posttraumatic stress symptoms,
      depression, and anxiety) in a sample of 120 inner-city African American
      adolescents (ages 10 to 14). Increased community violence was shown to be related
      to the use of negative coping strategies (avoidance, aggression, and
      internalizing behaviors), which mediated the relation between violence and all
      three outcomes.

PMID- 14964600
TI  - What does getting better mean? Child improvement and measure of outcome in
      residential treatment.
AB  - A single-sample, within-subject descriptive study was completed to ascertain
      individual subject characteristics associated with outcome for 87 youths
      discharged from a residential treatment facility. Two different methods of
      assessing outcome were also compared. Variables assessing a history of abuse and
      internalizing psychopathology at admission to residential care were associated
      with outcome. Low levels of staff agreement were found on the 2 outcome measures.
      Implications for acute residential care are discussed.

PMID- 14964601
TI  - Participation in social activities: maternal ratings of maltreated and
      nonmaltreated children.
AB  - Using the Achenbach Child Behavior Checklist (T. M. Achenbach, 1991), 192 mothers
      of maltreated children and 179 mothers of nonmaltreated children rated children's
      participation in social activities. Maltreated children were reported as
      belonging to fewer organizations and were judged less proficient at sports than
      nonmaltreated children. Regarding specific types of activities, maltreated
      children were rated as less likely to take part in team sports and to belong to
      sports organizations. Psychosocial disadvantage may reduce opportunities for
      maltreated children to participate in social activities.

PMID- 14964602
TI  - Risk factors for deliberate self-harm among college students.
AB  - This self-report study examined the risk factors for deliberate self-harm among
      college students. Results indicated that insecure attachment, childhood
      separation, emotional neglect, sexual abuse, and dissociation were significant
      predictors of self-harm. Substantial gender differences in the risk factors for
      self-harm behavior were also revealed. Suggestions for future research are
      provided.

PMID- 14964603
TI  - State-funded abortions versus deliveries: a comparison of outpatient mental
      health claims over 4 years.
AB  - In this record-based study, rates of 1st-time outpatient mental health treatment
      for 4 years following an abortion or a birth among women receiving medical
      assistance through the state of California were compared. After controlling for
      preexisting psychological difficulties, age, months of eligibility, and the
      number of pregnancies, the rate of care was 17% higher for the abortion group (n
      = 14,297) in comparison with the birth group (n = 40,122). Within 90 days after
      the pregnancy, the abortion group had 63% more claims than the birth group, with
      the percentages equaling 42%, 30%, and 16% for 180 days, 1 year, and 2 years,
      respectively. Additional comparisons between the abortion and birth groups were
      conducted on the basis of claims for specific types of disorders and age.

PMID- 14964604
TI  - To give or not to give.

PMID- 14964605
TI  - Organ donation and neuroscience nursing: your role in the process.
AB  - The death of a patient is seen by many nurses as the end of their interaction
      with the patient and family. However, the option of organ donation may extend
      that interaction and present another opportunity to serve as an advocate for the
      family, as well as for patients whom the nurse has never met. Patients who have
      been declared brain dead or from whom life support is going to be withdrawn
      following a neurological injury are potential organ donors. Although these
      patients and their families are frequently under the care of neuroscience nurses,
      all nurses need a thorough understanding of their responsibilities regarding
      identification and referral of potential organ donors to the designated Organ
      Procurement Organization (OPO). In addition, it is essential for nurses to
      understand the clinical presentation and determination of brain death in order to
      provide patient care and family education. Understanding how consent for organ
      donation should be obtained from families and how the organ recovery process
      works enables the nurse to collaborate with OPO staff and support the family in
      their decision regarding organ donation.

PMID- 14964606
TI  - Promoting wellness for women with multiple sclerosis.
AB  - There is increasing interest in wellness programs among health care providers and
      consumers. A unique intervention program was developed to promote wellness for
      women with multiple sclerosis (MS). Key processes include: provision of accurate
      knowledge that is specific to health promotion within the context of MS;
      enhancement of self-efficacy for health behaviors and individualized goal setting
      and monitoring. Participants have reported positive changes as a result of this
      two-phase (knowledge/skill building classes and telephone follow-up)
      intervention.

PMID- 14964607
TI  - Factors that contribute to complications during intrahospital transport of the
      critically ill.
AB  - Transporting patients from the protective environment of the intensive care (ICU)
      unit to other areas of the hospital has become increasingly common since high
      technologic testing has become an integral part of health care assessment. The
      hazards of moving critically ill patients by ambulance or air transport are well
      recognized and standards of care have been developed based on delineation of
      these risks. Despite the existing evidence of hazards of interhospital hospital
      transport, less attention has been given to the potential hazards associated with
      the intrahospital transport of critically ill patients. A high incidence of
      serious hemodynamic or respiratory alteration is associated with the
      intrahospital transport of critically ill patients. In one third of critically
      ill intrahospital transports, technical mishaps (eg, i.v. disconnects, which
      could potentially lead to deleterious physiologic outcomes) may occur. As patient
      acuity increases, there is a greater risk of hemodynamic instability. The purpose
      of this study was to further investigate the patient complications during
      transportation to and from the ICU to a diagnostic or treatment site. The sample
      consisted of thirty-five critically ill patients from the Neuro/Trauma ICU who
      required continuous physiological monitoring and had an arterial catheter in
      place. The systemic blood pressure, heart rate and peripheral oxygen saturation
      were monitored at nine time points throughout the transport process. The
      incidence of defined technical mishaps that occurred when the patient was off the
      unit were also recorded. Transport factors examined included the length of time
      spent off the unit and the number and level of personnel accompanying the
      patient. A within-subject repeat measure design was used to examine the
      physiologic changes and mishaps that occurred. Results indicate that while the
      majority of patients experienced some physiologic responses as a result of
      transport, the responses were not of sufficient magnitude to be classified as a
      deleterious. Twenty-three technical mishaps, which included inadvertent
      ventilator and electrocardiogram disconnects, power failures, interruption of
      medication administration and disconnection of drainage devices were observed.
      Factors related to these occurrences of technical mishaps were the number of
      intravenous solutions and infusion pumps and the time spent outside of the ICU
      environment.

PMID- 14964608
TI  - Neurologic mechanisms in psychoneuroimmunology.
AB  - Synthesizing the neurologic mechanisms of psychoneuroimmunology (PNI) into a
      schematic model serves as a basis to enhance understanding of the complex
      interactions within the PNI framework. The examination of current research in
      physiology, neurotransmission, hormonal mechanisms, immunologic function and
      stress allows for the creation of a neurological model to depict hypothetical
      interactions of these systems. This model of neurological mechanisms in PNI can
      serve as the basis for integrating PNI in nursing practice. It is hoped that the
      model will serve as a bridge to understanding the neuroscience component of PNI
      and stimulate further research.

PMID- 14964609
TI  - Secondary mechanisms in traumatic brain injury: a nurse's perspective.
AB  - Effective management of brain-injured patients requires that nurses have a
      specialized body of knowledge relating to the pathophysiology and treatment of
      traumatic brain injury (TBI). Current research in this area has focused on the
      cascade of secondary injury which leads to the irreversible tissue damage
      following TBI. Such processes involve excitatory amino acids, neurotransmitters,
      ion changes, lipid peroxidation, oxygen free radicals, opioids, lactic acidosis
      and magnesium to name but a few. Given that no accepted treatment paradigm exists
      to attenuate these secondary processes, nurses may have to autonomously devise
      individual care plans based on their current understanding of brain injury
      pathophysiology.

PMID- 14964610
TI  - Psychosocial issues for spouses of brain injury survivors.
AB  - Brain injury has a profound effect on the family system. When the survivor is a
      spouse, the impact is especially devastating. Roles in the family are changed,
      responsibilities are shifted and economic stability is often challenged. The
      noninjured spouse frequently faces these difficult circumstances without the
      customary support of his or her marriage partner. The cognitive and behavioral
      changes which are associated with brain injury alter the survivor as a person.
      This creation of a "new" member of the family system necessitates major
      adjustments as this individual is reincorporated into the family. It is not
      unusual for friction to develop between the noninjured spouse and the in-laws.
      Because the experience of spouses is different from the experience of parents of
      persons with brain injury they may benefit from a mutual support group
      exclusively for spouses.

PMID- 14964611
TI  - International perspectives on stroke rehabilitation.

PMID- 14964612
TI  - A critical review of techniques aiming at enhancing and sustaining worker's
      alertness during the night shift.
AB  - Two types of methods based on a particular principle allow enhancing and
      sustaining workers' alertness all along their night work. The first one rather
      consists in arousing workers by exposing them to stimulant environment conditions
      (light or noise...) or by giving them natural or pharmacological reactivating
      substances (caffeine or amphetamines...) for example. The second principle
      consists in increasing workers' possibilities for resting and allowing them to
      have short sleep periods or Short Rest Periods (SRP) in an adapted area at the
      workplace. In order to use these techniques in real work situations, after a
      critical review taking into account both efficiency, advantages and disadvantages
      but also applicability and acceptability, the SRP technique stands out as the
      most efficient method as it has a certain number of advantages with regard to our
      initial objective.

PMID- 14964613
TI  - Shape and thickness of cushion in a standing aid to support a forward bending
      posture: effects on posture, muscle activities and subjective discomfort.
AB  - In order to prevent low back pain (LBP) during dishwashing, we developed three
      types of aid with a thick cushion for supporting the shins and evaluated the
      effects of the standing aid on the subjective discomfort and muscle activities.
      Nine female volunteers were asked to wash plates in each of four working
      postures: (a) without the standing aid, (b) with the round type of aid, (c) with
      the small rectangular type of aid, and (d) with the large rectangular type of
      aid. With the three types of aid, the subjects were instructed to support the
      shins with the standing aid and to support the abdomen with the edge of a kitchen
      counter. In the three postures with the standing aid, 21.5 +/- 10.0% of the
      weight was supported with the standing aid and the kitchen counter. The
      subjective discomfort was milder and the muscle activity level in the low back
      was lower in the three postures with the standing aid than in the posture without
      the aid. It was thought that the round type of aid would be more effective in
      decreasing the discomfort in many of body regions and the muscle load on the low
      back than either of the rectangular types of aid. Therefore, it was suggested
      that the standing aid had the desired effect in decreasing discomfort and muscle
      load on the low back during dishwashing.

PMID- 14964614
TI  - Medial plantar nerve conduction velocities among patients with vibration syndrome
      due to rock-drill work.
AB  - OBJECTIVE: The present study was aimed at clarifying the effect of vibration
      syndrome (VS) on the peripheral nervous system in the lower extremities of
      patients with VS due to rock-drill work. METHODS: Fifty-three patients with VS
      due to previous exposure to vibration from rock-drilling work and 55 age-matched
      controls were examined for sensory nerve conduction velocities in the medial
      plantar nerve (SCV-P). The patient group was divided into three subgroups,
      outdoor rock-drill workers with vibration-induced white finger (VWF) (N = 10),
      tunnel workers with VWF (N = 27) and tunnel workers without VWF (N = 16).
      RESULTS: ANOVA of SCV-P for the four groups showed F = 3.23 (dF = 3, 104, p =
      0.0253). A significant difference was found between the controls and outdoor rock
      drill workers with VWF group (p = 0.0261) by multiple comparison using Scheffe's
      method. CONCLUSION: These findings suggest that peripheral nervous system
      function in the lower extremities of patient with VS is affected by cold exposure
      and circulatory disturbance manifested as VWF.

PMID- 14964615
TI  - Evaluation of workers' exposure to total, respirable and silica dust and the
      related health symptoms in Senjedak stone quarry, Iran.
AB  - The present research was conducted in a stone quarry of marble located in
      northeast of Iran. Time weighted average of total dust, respirable dust, and
      crystalline silica (alpha-quartz) concentration in workers' breathing zone were
      monitored by using both gravimetric and XRD methods. The results showed that the
      employees working in hammer drill process had the highest exposure to the total
      and respirable dust: 107.9 +/- 8.0 mg/m3, 11.2 +/- 0.77 mg/m3 respectively, while
      the cutting machine workers had the lowest exposure (9.3 +/- 3.0 mg/m3, 1.8 +/-
      0.82 mg/m3). The maximum concentration of a-quartz in total and respirable dust
      were detected equal to 0.670 +/- 8.49 x 10(-2) and 5.7 x 10(-2) +/- 1.6 x 10(-2)
      mg/m3 respectively, which belonged to the exposure of the workers of hammer drill
      process. The prevalence of skin and respiratory symptoms were higher in hammer
      drill workers, however, respiratory symptoms showed no significant prevalence.
      Regarding the average age of workers (31.6 +/- 1.9 yr) and average of their work
      history (3.8 +/- 1.0 yr), these results were predictable.

PMID- 14964616
TI  - Effects of changing shift schedules from a full-day to a half-day shift before a
      night shift on physical activities and sleep patterns of single nurses and
      married nurses with children.
AB  - To clarify the effects of changing shift schedules from a full-day to a half-day
      before a night shift, 12 single nurses and 18 married nurses with children that
      engaged in night shift work in a Japanese hospital were investigated. Subjects
      worked 2 different shift patterns consisting of a night shift after a half-day
      shift (HF-N) and a night shift after a day shift (D-N). Physical activity levels
      were recorded with a physical activity volume meter to measure sleep/wake time
      more precisely without restricting subjects' activities. The duration of sleep
      before a night shift of married nurses was significantly shorter than that of
      single nurses for both shift schedules. Changing shift from the D-N to the HF-N
      increased the duration of sleep before a night shift for both groups, and made
      wake-up time earlier for single nurses only. Repeated ANCOVA of the series of
      physical activities showed significant differences with shift (p < 0.01) and
      marriage (p < 0.01) for variances, and age (p < 0.05) for a covariance. The
      paired t-test to compare the effects of changing shift patterns in each subject
      group and ANCOVA for examining the hourly activity differences between single and
      married nurses showed that the effects of a change in shift schedules seemed to
      have less effect on married nurses than single nurses. These differences might
      due to the differences of their family/home responsibilities.

PMID- 14964617
TI  - The influence of work characteristics on body mass index and waist to hip ratio
      in Japanese employees.
AB  - A cross-sectional study on 6,676 workers consisting of 4,243 males and 2,433
      females aged 20-58 yr in a metal product factory was conducted to elucidate the
      relationship between work characteristics, e.g. job demand/control/support,
      sedentary job, overtime work and shift work, and waist to hip ratio (WHR) as well
      as body mass index (BMI) taking alcohol consumption, smoking, exercise and other
      psychosocial factors such as education and marital status into account. By a
      stepwise multiple regression analysis, BMI was associated with shift work,
      marital status and sedentary job for males, and with exercise but inversely
      associated with education for females. WHR was also associated with shift work,
      alcohol consumption, marital status and sedentary job but inversely associated
      with exercise for males, and with sedentary job, marital status and education but
      inversely associated with smoking for females. These results suggest that work
      characteristics such as sedentary job and shift work should also be considered
      when trying to prevent increases in BMI and WHR.

PMID- 14964618
TI  - A study on a reduction in visits to physicians after introduction of 30% co
      payments in the employee health insurance in Japan.
AB  - The purpose of the study is to evaluate influences of the introduction of 30% co
      payments on potential visit behavior using a questionnaire in order to determine
      whether "employment state of the spouse" and "number of dependent children", as
      indicators of economic backgrounds, affect visits to physicians in a health
      insurance society. The subjects were 1,674 insured consisting of 1,165 males and
      509 females, who underwent a regular health examination in July 2002, in a health
      insurance society. In the survey, they were asked whether the subject "will
      reduce" or "will not reduce" visits to physicians due to the increase in co
      payments in the health insurance system scheduled in 2003. Multivariate analyses
      showed that "employment state of the spouse" was significantly related to the
      reduction in visits for myocardial infarction or stroke, cancer or heart disease,
      and hypertension and diabetes mellitus. Concerning "number of dependent
      children", it was related to the risk of reducing visits to physicians for
      myocardial infarction or stroke, trauma or fracture, cancer or heart disease, and
      low back pain or knee pain. Finally, upper limit expenditures of co-payments of
      physicians to visits due to hypertension and diabetes mellitus were related to
      "number of dependent children". The study results suggest that "employment state
      of the spouse" and "number of dependent children" are significant factors to
      affect potential visits to physicians after the introduction of 30% co-payments.

PMID- 14964619
TI  - Fatigue and its underlying factors among elderly citrus farmers in a rural area
      of Japan--effect of social support on fatigue and gender difference.
AB  - The purposes of this study were to assess fatigue among elderly citrus farmers
      and indicating countermeasures to reduce the workload of agricultural work and
      the work-related stress among elderly citrus farmers. The Fatigue Questionnaire
      for Farmers developed by the Rural Life Research Institute, Japan was used after
      a modification by the addition of items related to dietary life. It was found
      that some of the factors causing fatigue among citrus farmers differed between
      men and women. There was a clear correlation between agricultural work load and
      the severity of fatigue. Among these elderly farmers, the qualitative aspect of
      work stress had much more effect on fatigue than the quantitative aspect. And,
      the fact that social support impossibility for them deepened their sense of
      dissatisfaction with work and social life indicated the importance of social
      support for them. The study suggested that the modified questionnaire was shown
      to be useful in the assessment of fatigue among agricultural workers; however, it
      needs to be simplified. Further study using the simplified fatigue questionnaire
      is needed for further clarification of fatigue and its underlying factors among
      agricultural workers.

PMID- 14964620
TI  - Effects of seat-back angle and accelerometer height at the seat-back on seat-back
      x axis r.m.s. acceleration in filed experiments according to the ISO2631-1
      standard.
AB  - The effects of seat-back angle and accelerometer height at the seat-back on seat
      back x-axis frequency-weighted root-mean-square (r.m.s.) acceleration have been
      investigated in field experiments. Experiment 1 investigated the range and
      variability, of frequency-weighted r.m.s. acceleration at the same measurement
      position, where the seat-back angle was 24 degrees from vertical on the floor and
      the accelerometer height was 38 cm up from the seat cushion surface. Experiment 2
      investigated ranges of frequency-weighted r.m.s. acceleration between the
      reference position, which was the position used in experiment 1, and test
      positions at different seat-back angles, 4 degrees ahead of and 4 degrees behind
      the reference position. Experiment 3 investigated the range of frequency-weighted
      r.m.s. acceleration between the reference position which was the same as in
      experiments 1 and experiment 2, and test positions at different accelerometer
      heights at the seat-back from a seat cushion surface, 2.5 cm higher, 2.5 cm lower
      and 5 cm lower than the reference position. This investigation clarifies that
      different seat-back angles and accelerometer heights at the seat-back affect the
      frequency-weighted r.m.s. acceleration at these measurement positions, which is
      beyond the exposure values at which people are able to distinguish different
      vibration acceleration magnitudes.

PMID- 14964621
TI  - Toluene alters p75NTR expression in the rat brainstem.
AB  - Toluene is a neurotoxic organic solvent widely used in industry. Acute toluene
      administration in rats induced a significant increase in the numbers of neural
      cells immunostained for p75NTR in several brainstem regions, such as the raphe
      magnus and the nucleus of the solitary tract, as well as in the lateral
      reticular, gigantocellular, vestibular and ventral cochlear nuclei, without any
      in the facial and spinal trigeminal nuclei and the dorsal horn of the spinal
      cord. These data suggest that p75NTR could be involved in toluene-induced
      neurotoxic efffects in the rat brainstem.

PMID- 14964622
TI  - Influence of waterproof covering on finger skin temperature and hand pain during
      immersion test for diagnosing hand-arm vibration syndrome.
AB  - The purpose of this study was to examine the influence of waterproof covering on
      finger skin temperature (FST) and hand pain during immersion test for diagnosing
      hand-arm vibration syndrome complying with the proposal of the International
      Organization for Standardization (ISO/ CD14835-1, 2001) for measurement
      procedure. Six healthy male subjects took part in the immersion tests and
      immersed their both hands into water at 12 degrees C for 5 min, repeatedly with
      two types of waterproof covering (polyethylene and natural rubber gloves) or
      without hand covering (bare hands) during immersion. The FST data from middle
      fingers and subjective pain scores for hand pain were analyzed. Statistically
      significant differences in FST among three conditions were observed showing the
      highest FST with natural rubber gloves, followed by the FST with polyethylene
      gloves and the lowest with bare hands. Significant differences in pain score
      among three conditions were observed during immersion showing the lowest pain
      score with natural rubber gloves, followed by the pain score with polyethylene
      gloves and the highest with bare hands. Immersion test with polyethylene gloves
      instead of bare hands during immersion seems to be suitable for reducing subject
      suffering.

PMID- 14964623
TI  - Neurologic sequela of hydrogen sulfide poisoning.
AB  - A 25-year-old man, a field operator in a petroleum refinery was found
      unconscious. He was exposed to hydrogen sulfide and presented with Glasgow Coma
      Score of 5, severe hypoxemia on arterial blood gas analysis, normal chest
      radiography, and normal blood pressure. On hospital day 7, his mental state
      became clear, and neurologic examination showed quadriparesis, profound
      spasticity, increased tendon reflexes, abnormal Babinski response, and
      bradykinesia. He was also found to have decreased memory, attention deficits and
      blunted affect, which suggested general cognitive dysfunction, but which improved
      soon. MRI scan showed abnormal signals in both basal ganglia and motor cortex,
      compatible with clinical findings of motor dysfunction.

PMID- 14964624
TI  - The British Association for Psychopharmacology guidelines for treatment of
      bipolar disorder: a summary.
AB  - The BAP has provided a review of the research evidence and clinical experience in
      the treatment of bipolar disorder. It has produced guidelines that give very real
      practical advice to clinicians in the day-to-day management of this difficult
      condition. Its recommended enhancement of routine care may well increase
      adherence to treatment, especially if the patient is involved in choice of
      medicine, leading to lower overall morbidity. It is timely since awareness of the
      specific needs of bipolar patients is growing and there is an increased choice of
      effective treatments for all phases of the illness.

PMID- 14964625
TI  - Bipolar disorder ignored by the Mental Health National Service framework but not
      forgotten by the British Association for Psychopharmacology.
AB  - Bipolar disorder (BD) is a severe mental illness that has been largely ignored by
      the National Service Framework (NSF) for Mental Health. This is particularly
      notable because it is associated with a higher suicide rate than schizophrenia
      and has a greater burden of disability. The NSF offers little guidance on service
      models that specifically consider BD. This is of concern because of the
      complexities that are inherent in the management of BD. These deficiencies in the
      NSF may have far-reaching implications for resource allocation, service
      organization, and patient management and well-being. Moreover, the standards and
      performance targets laid out in the NSF will be difficult to meet if this
      important and common mental illness is not specifically catered for in mental
      health services. Local Implementation Teams would be well advised to take note of
      the recently published British Association for Psychopharmacology guidelines for
      the management of BD.

PMID- 14964626
TI  - Human currency, Part III: The tightrope.

PMID- 14964627
TI  - What is your diagnosis? Waardenburg syndrome.

PMID- 14964628
TI  - Cutaneous laser surgery in darker skin phototypes.
AB  - Effective laser surgery in patients with darker skin phototypes can be achieved
      despite a greater inherent risk of side effects. Although the incidence of
      undesirable postoperative sequelae has decreased with the development of advanced
      laser technology and individualized treatment parameters, the risks may never be
      eliminated completely. Therefore, thorough patient preoperative preparation and
      education regarding the risks of cutaneous laser surgery will remain an essential
      aspect of treatment in patients with darker skin tones. As more refined laser
      techniques evolve, the ability to safely and effectively treat these patients
      will continue to improve.

PMID- 14964629
TI  - Pimecrolimus cream 1%: a potential new treatment for chronic hand dermatitis.
AB  - A multicenter, randomized, vehicle-controlled, 3-week study was conducted in
      patients with chronic hand dermatitis (HD) of various etiologies and locations to
      identify subgroups particularly responsive to twice-daily application of
      pimecrolimus cream 1% with overnight occlusion. A total of 294 patients were
      randomized to the study. By the final visit on day 22, there was a trend toward
      greater clearance in patients who received pimecrolimus than in those treated
      with vehicle cream. An analysis of treatment success by various stratification
      factors was performed, and it was found that palmar involvement had notable
      impact on response (P = .033). Patients in the pimecrolimus group continued to
      improve throughout the study; however, in the vehicle group, improvement
      plateaued after 15 days. Pimecrolimus was well tolerated, with a low rate of
      application-site reactions such as burning. Pimecrolimus cream 1%, when used
      twice daily with overnight occlusion, may be of benefit in the management of
      chronic HD.

PMID- 14964630
TI  - Rhabdomyosarcoma arising in a giant congenital melanocytic nevus.
AB  - We report the case of a 6-week-old girl who presented with a pedunculated
      embryonal rhabdomyosarcoma arising in a giant congenital melanocytic nevus (GCMN)
      on her lower back. There was no associated leptomeningeal involvement. The
      patient underwent surgical resection of the rhabdomyosarcoma at age 2 months,
      with subsequent chemotherapy consisting of actinomycin D and vincristine. No
      recurrences or metastases of tumor have been noted at 5 months of age.

PMID- 14964631
TI  - Necrotizing fasciitis and cardiac catheterization.
AB  - Necrotizing fasciitis (NF) is an uncommon, life-threatening soft tissue infection
      characterized by rapidly spreading inflammation and necrosis of the skin,
      subcutaneous tissue, and fascia. We report a case of NF as a complication of
      cardiac catheterization. Familiarity with this entity may lead to earlier
      diagnosis and initiation of appropriate therapy.

PMID- 14964632
TI  - Cutaneous sarcoidosis at sites of previous laser surgery.
AB  - A 33-year-old patient was referred for evaluation and treatment of enlarging
      scars in areas where full-face carbon dioxide (CO2) laser resurfacing had been
      performed previously. The patient denied any systemic illness and was in good
      health at the time of presentation. This is a case report of isolated sarcoidosis
      limited to the skin associated with CO2 laser resurfacing.

PMID- 14964633
TI  - Cutaneous sarcoidosis presenting as leonine facies.
AB  - Cutaneous sarcoidosis often masquerades as many other disease entities. We
      describe the case of a 56-year-old African American man with a 1-year history of
      progressively enlarging nodules and plaques of the face resulting in a leonine
      appearance and madarosis. The diagnosis of cutaneous sarcoidosis was made after
      skin biopsy results revealed noncaseating granulomas without evidence of foreign
      body, mycobacteria, or deep fungal infection. A thorough systemic workup was void
      of other comorbidities. The reports of tumoral sarcoidosis or sarcoidosis
      presenting with leonine facies are rare, and those cases that have been reported
      have been linked to other systemic findings.

PMID- 14964634
TI  - Vancomycin-induced linear IgA bullous dermatosis: morphology is a key to
      diagnosis.
AB  - Vancomycin-induced linear IgA bullous dermatosis (LABD) previously has been
      described; however, past reports have suggested that the clinical presentation is
      nonspecific. We present a case of vancomycin-induced LABD with a suggestive
      clinical presentation; specifically, groups of annularly arranged vesicles. We
      propose that this clinical presentation strongly suggests drug-induced LABD and
      should raise a clinician's suspicion of vancomycin as the offending agent. This
      awareness may guide the antibiotic management of the patient while the clinician
      awaits histopathologic correlation.

PMID- 14964635
TI  - The integrity of dermatology applicants.

PMID- 14964636
TI  - Photo recall effect in association with cefazolin.
AB  - Patients in remission from local dermatitis secondary to external beam radiation
      treatments occasionally experience recurrence with systemic chemotherapy, a
      reaction termed radiation recall. Chemotherapy-induced photo recall from a prior
      exposure to the sun also has been reported. Rare reports describe photo recall
      effects from more commonly used medications. We report the case of a patient who
      developed a photo recall reaction after treatment with cefazolin. Results of the
      shave biopsy were consistent with a mild phototoxic eruption.

PMID- 14964637
TI  - Managing simple chronic paronychia and onycholysis with ciclopirox 0.77% and an
      irritant-avoidance regimen.
AB  - Dermatologists and other physicians frequently encounter simple chronic
      paronychia and onycholysis. In addition to strict avoidance of contact irritants,
      a broad-spectrum topical antifungal agent has been recommended. We conducted an
      examination of treatment with this type of agent and an assessment of the
      efficacy of ciclopirox 0.77% topical suspension in combination with a strict
      irritant-avoidance regimen. Early results of a pilot study (N = 44) using
      ciclopirox 0.77% topical suspension in patients diagnosed with simple chronic
      paronychia and/or onycholysis show excellent therapeutic outcomes of a combined
      regimen of a broad-spectrum topical antifungal agent such as ciclopirox and
      contact-irritant avoidance in this patient population.

PMID- 14964638
TI  - Advances in molecular immunotoxicology of occupational asthma induced by low
      molecular weight chemicals.
AB  - The paper reviews the literature reports on low molecular weight (LMW)
      sensitizers that are commonly encountered in the work environment as well as on
      the major mechanisms responsible for their effect on the immune cells of the
      respiratory tract. Current studies have focused on: LMW-antigens; the role of
      airway epithelial and dendritic cells (DCs); activation of naive helper T (Th)
      cells by DCs; naive B cell-effector Th2 cell interactions; and activation of mast
      cells by LMW asthmogens. A better understanding of the pathogenesis of
      occupational asthma due to LMW asthmogens should facilitate the development of
      better diagnostics and the improvement of strategies for disease surveillance and
      intervention.

PMID- 14964639
TI  - Effects of occupational exposure to aluminum on nervous system: clinical and
      electroencephalographic findings.
AB  - OBJECTIVES: The aim of the present study was to assess the effects of aluminum
      (Al) on the nervous system functions in workers chronically exposed to Al.
      MATERIALS AND METHODS: The study covered a selected group of 67 male workers
      (mean age, 38.7 SD 10.3 years; range 23-55 years) involved in the Al production.
      Their employment duration ranged between 2 and 34 years (mean, 14.6 SD 8.9
      years). Aluminum oxide (Al203) concentrations varied from 0.13 to 1.95 mg/m3
      (arithmetic mean, 0.40 mg/3, geometric mean, 0.35 mg/m3 SD 0.29). Urine Al
      concentrations found in smelters ranged from 8.5 to 93.0 microg/l (mean, 42.9 SD
      20.5 microg/l). The control group consisted of 57 men non-occupationally exposed
      to Al, matched by gender, age and work shifts. RESULTS: Clinically, headache
      (41.8%), increased emotional irritability (56.7%), concentration difficulty
      (22.4%), insomnia (22.4%) and mood lability (14.9%) predominated among functional
      disorders of the nervous system in workers chronically exposed to Al. Objective
      neurological examinations did not reveal organic lesions in the central or
      peripheral nervous system. In the EEGs classified as abnormal, generalized and
      paroxysmal changes were most common. CONCLUSIONS: The results of this study
      suggest that exposure to Al203 at concentrations below MAC values induces
      subclinical effect in the nervous system.

PMID- 14964640
TI  - Repeatability of vibrotactile perception thresholds obtained with two different
      measuring systems.
AB  - OBJECTIVES: The measurement of vibrotactile perception thresholds (VPTs) on the
      workers' fingertips is one of the diagnostic methods of the occupational
      peripheral neuropathies. The aim of the study was to compare the repeatability of
      VPT measurements in two groups of healthy women with different finger skin
      temperature, using two different types of measuring systems. MATERIALS AND
      METHODS: One measuring system employed a pallesthesiometer, and the measurement
      procedure complied with the new ISO 13091-1 standard; the other used vibrotactile
      meter according to the Polish procedure. Ten healthy women, mean age, 38.5 years,
      took part in 10 sessions, twice a day for over a five-day period. VPTs were
      measured on 3 fingers of both hands at eight discrete frequencies from 4 to 500
      Hz with a pallesthesiometer, and adequately at five frequencies from 63 to 500 Hz
      with a vibrotactile meter. RESULTS: It was observed that the succession of
      repeated vibration perception measurements, determined according to the ISO
      method, did not significantly influence the mean values of vibrotactile
      thresholds in subjects with the finger skin temperature not lower than 29degrees
      C. The repeatability of vibrotactile threshold measurements was similar in both
      groups only when the ISO method was used. The mean VPT values, obtained with the
      ISO 13091-1 method, were significantly higher in healthy subjects with lower
      finger skin temperature, which did not exceed 28 degrees C. CONCLUSIONS: The
      results of vibrotactile threshold measurements, obtained according to the ISO
      13091-1 method, are repeatable. Repeatability of vibrotactile threshold results
      obtained with the ISO 13091-1 method, within the range of low frequencies up to
      125 Hz does not depend on the finger skin temperature.

PMID- 14964641
TI  - Exposure to dust and its particle size distribution in shoe manufacture and
      repair workplaces measured with GRIMM laser dust monitor.
AB  - OBJECTIVES: Owing to a diversified technological process and a great variety of
      products and materials used in shoe manufacture, workers may be exposed to dusts
      that contain different chemicals and particles of various shapes and sizes. The
      aim of this study was to assess the dust exposure, taking account of
      concentration of particular size fractions according to the European Standard
      Norm, and to analyze particle size distribution in inhalable dust at selected
      workplaces in a modern shoe manufacture plant and in a small shoe repair workshop
      in comparison with other industrial branches. MATERIALS AND METHODS: In these two
      workplaces, the concentrations of dust, representing the inhalable, thoracic, and
      respirable fractions, were measured with the GRIMM 1.105 laser dust monitor.
      RESULTS: The particle size distribution in inhaled dust in the most
      characteristic workposts was analyzed. In the shoe manufacture plant, the
      concentrations ranged from 124 microg/m3 (leather cutting out) to 724 microg/m3
      (scouring and milling of soles); concentrations of the thoracic and respirable
      fractions in the same workposts ranged from 74 microg/m3 to 412 microg/m3 and
      from 24 microg/m3 to 120 microg/m3, respectively. In the shoe repair workshop,
      the recorded concentrations were higher: the values ranged from 521 microg/m3
      (gluing of shoes and soles, zipper exchange and heel abrasion) to 916 microg/m3
      (uppers sewing and heel scouring) for the inhaled fraction; from 335 microg/m3 to
      499 microg/m3 for the thoracic fraction; and from 88 microg/m3 to 120 microg/m3
      for the respirable fraction. The mass median aerodynamic diameters of inhalable
      dust particles fell within the limits of 6.2-25.0 mm. Dust with the smallest
      particles (MMAD = 6.2 mm) was observed in shoe brushing and polishing, and with
      the largest particles (MMAD = 25.0 mm) in uppers sewing. CONCLUSIONS: The modern
      process of shoe manufacture is characterized by very low concentrations of
      inhalable dust and its fractions, they are considerably lower than occupational
      exposure limits in Poland for inhaled (4000 microg/m3) and respirable (2000
      microg/m3) dust. In the workplaces under study, a relatively high proportion of
      extrathoracic fraction of leather dust was found, which supports a hypothesis on
      a potential etiologic role of this factor in the development of pathologies in
      the upper airways region.

PMID- 14964642
TI  - Profiles of occupational exposure in patients with wood dust-induced nasal
      carcinoma.
AB  - OBJECTIVES: Regulations to certify nasal carcinoma as occupational disease
      induced by wood dust vary in the European countries. In Germany, it must be
      adenocarcinoma and the dust originating from beech or oak trees. In other
      countries, the disease is reconized as induced by occupation independent of the
      kind of wood dust or the type of carcinoma. With regard to the harmonization of
      regulations necessary in Europe we investigate whether these differences are
      acceptable from the scientific viewpoint. MATERIALS AND METHODS: In a
      retrospective analysis of a group of 28 patients with wood dust-induced nasal
      carcinoma in North Rhine-Westphalia, Germany, we studied whether significant
      differences in exposure, personal risks (smoking) and histological tumor type
      could justify the current German, Austrian and Luxembourg pattern of occupational
      disease certification. To quantify cumulative time of exposure we developed a new
      semiquantitative formula for the calculation of wood dust years (WDY). RESULTS:
      Our results indicate that there are no significant differences between the
      subgroups, i.e., exposure to hard wood (n = 13) or other woods (n = 15), WDY
      (13.1 +/- 11.3), smoking (n = 17) or nonsmoking, type of work and the diagnosis
      of nasal squamous cell carcinoma (n = 8) versus nasal adenocarcinoma (n = 20).
      The review of literature suggests systematic errors in the studies that led to
      the current German regulations. CONCLUSIONS: We recommend to amend the German,
      Austrian and Luxembourg regulations and to recognise nasal carcinomas as
      occupational disease, regardless of the type of wood dust exposure, and
      regardless of the tumor histology as also recommended by the International Agency
      for Research on Cancer (IARC).

PMID- 14964643
TI  - Assessment of annoyance from low frequency and broadband noises.
AB  - OBJECTIVES: It has been shown that low frequency noise (LFN), defined as
      broadband noise with dominant content of low frequencies (10-250 Hz), may be
      annoying to exposed subjects. The aim of the study was to compare the degree of
      annoyance caused by LFN with that caused by broadband noise (BBN) without
      dominant low frequency components at similar A-weighted sound pressure levels.
      MATERIALS AND METHODS: Subjects included in the study were 145 male employees of
      the control rooms. They were exposed to noise through headphones at gradually
      increasing dB A-weighted sound pressure levels within the range of 62-84 dB.
      Annoyance rating was based on a 100-score graphical scale. RESULTS: LFN was rated
      as significantly more annoying than BBN at the comparable A-weighted sound
      pressure levels. The annoyance assessment of either noise did not depend on age,
      length of employment or the level of exposure to noise at a current workplace.
      CONCLUSIONS: LFN represents a higher risk of influencing human well-being than
      regular BBN and should be considered in the occupational exposure assessment.

PMID- 14964644
TI  - Combined exposure to m-xylene and ethanol: oxidative stress in the rat liver.
AB  - OBJECTIVES: Ethanol may be a significant combined factor in human solvent
      toxicity. Lipid peroxidation has been suggested to be an important contributing
      mechanism involved in experimental alcohol-induced liver injury. The aim of the
      study was to investigate whether a short-term ethanol ingestion in rats
      chronically exposed to m-xylene vapor may influence the lipid peroxidation rate
      in the intracellular hepatic membranes, the level of glutathione and the activity
      of glutathione-related enzymes in the liver. MATERIALS AND METHODS: Experiments
      were performed on male Wistar rats (outbred IMP:WIST) exposed to m-xylene (5
      months, 5 h/day), at a low concentration (400 mg/m3), and/or acute ethanol
      administration (6 oral doses of 0.25 g/100 g b.w. at 12 h intervals, for the last
      3 days of xylene exposure). To estimate the oxidative stress in the liver, lipid
      peroxidation rate in microsomal and lysosomal membranes, glutathione sulfhydryls
      levels, and glutathione-S-transferase activity were determined. RESULTS: The
      studies indicated that combined exposure to ethanol and m-xylene, as distinct
      from the chronic exposure to m-xylene alone, led to the increased lipid
      peroxidation rate in microsomal and lysosomal membranes with a simultaneous
      decrease in the levels of glutathione sulfhydryls and glutathione-S-transferase
      activity. CONCLUSIONS: We conclude that the enhanced lipid peroxidation rate in
      the intracellular hepatic membranes may be an important agent in combined
      ethanol/xylene-induced hepatotoxicity.

PMID- 14964645
TI  - Tissue distribution, excretion and metabolism of o-anisidine in rats.
AB  - OBJECTIVES: The principal commercial use of o-anisidine is believed to be as an
      intermediate in the manufacture of dyes. It has also been reported to be an
      intermediate in the manufacture of synthetic guaiacol and its derivatives. o
      Anisidine is an urinary bladder carcinogen in mice and rats. The aim of the study
      was to investigate the kinetics of body distribution, excretion and
      biotransformation of o-anisidine in rats following a single, intraperitoneal
      administration. MATERIALS AND METHODS: The tissue distribution and excretion of o
      anisidine following i.p. administration of a single dose of 10 mg/kg was
      investigated using radiotracer [3H]. Metabolism of o-anisidine was investigated
      in the rats following i.p. administration of a single dose of 50 mg/kg using
      GC/MS technique. RESULTS: After 72 h, about 72% of the given dose was excreted in
      urine. As indicated, urine proved to be the main route of tritium excretion. In
      all examined tissues, the highest concentrations of tritium were found 12 h after
      injection and the highest accumulation was detected in the liver, kidneys and in
      the muscle tissue. In urine, the following substances were identified and
      quantified by GC peak areas: N-acetyl-2-methoxyaniline and N-acetyl-4-hydroxy-2
      methoxyaniline. CONCLUSIONS: Prolonged tritium retention observed in the majority
      of tissues indicated that o-anisidine, especially in the case of repeated
      exposure, might accumulate in the body. The metabolism encompasses amine group
      acetylation and ring oxidation.

PMID- 14964646
TI  - Adverse reproductive effects in female workers of lead battery plants.
AB  - Fifty seven female workers at mean age 32 years (range, 23-45 years), employed in
      a storage battery plant and a capacitor factory were investigated. The lead
      exposure period was 7.4 years (range, 1-17 years). The retrospective method was
      used to analyse reproductive functions of women: menses, libido, abortion and
      delivery. The results were compared with the control group (62 female workers,
      mean age 32 years; range, 24-45 years). The incidence of polymenorrhea, prolonged
      and abnormal menstruations, hypermenorrhea was significantly higher in the lead
      exposed group than in controls. The incidence of spontaneous abortions was
      reported by 6 exposed female workers whereas it was not observed in the control
      group (p = 0.01). The authors conclude that occupational lead exposure of female
      workers could lead to the impairment of the functions of reproductive system,
      however poor working conditions and workload may prove to be additional factors
      responsible for functional disorders in the subjects under study.

PMID- 14964647
TI  - Polish bibliography of occupational medicine, 2002.

PMID- 14964648
TI  - Soil characteristics as factors governing the existence, recycling and
      persistence of Bacillus thuringiensis in Egypt.
AB  - The simple correlation and regression analyses showed that the soil sand
      percentage and the available copper levels had significant negative and positive
      contributions, respectively, to the abundance and distribution of B.
      thuringiensis in the Egyptian agricultural soil. Among the B. thuringiensis
      isolates, only 11.26% of strains showed larvicidal activity against Culex
      pipiens. The larvicidal potency LD50 varied from 5.01X10(5) to 5.4X10(6) spores
      per milliliter among the isolates.

PMID- 14964649
TI  - Cytogenetics of acute and chronic schistosomiasis mansoni.
AB  - Schistosomiasis mansoni patients with acute were examined for genetic damage
      using the conventional cytogenetic method to assess the frequency of chromosomal
      aberration (CA) in the cultured blood cells. A non-significant difference was
      noticed in the frequency of CA between patients (acute & chronic) and control (n
      = 15), but on treatment of blood cultures with bleomycin (a radiomimetic agent
      with a DNA alkylating effect), the percentage of induced breakage and
      fragmentation increased significantly 2 and 3 folds in acute and chronic patients
      respectively, indicating increased chromosomal fragility. The incidence of
      rearrangement in the form of translocation increased significantly as compared to
      control blood cultures treated with bleomycin. The study revealed the antimitotic
      of schistosomiasis from significant inhibition of mitotic index. Although
      schistosomiasis did not show a direct clastogenic effect, it can be considered as
      a comutagen when there is concomitant exposure, especially chronic ones, to
      radiomimetic agents, schistosomiasis may amplify their cytogenetic damage.

PMID- 14964650
TI  - The effects of laboratory Hepatozoon gracilis infection on the fecundity,
      mortality and longevity of Culex (Culex) pipiens Linneaus (Diptera: Culicidae) in
      Egypt.
AB  - Laboratory observations on the effect of Hepatozoon gracilis on the egg
      production of the mosquito Cx. (Cx.) pipiens Linneaus under laboratory conditions
      revealed that H. gracilis infected mosquitoes produced significantly fewer eggs
      than uninfected ones. The egg production decreased as parasite burdens increased.
      Reduction in blood meal size in infected females did not reduce fecundity. No
      size differences was detected between oocyst-infected and uninfected females
      although sporozoite positive females were significantly large. Preoviposition
      period was affected significantly, while incubation period and percentage of egg
      hatching showed no significant changes. The longevity of female infected
      mosquitoes decreased insignificantly than in uninfected ones.

PMID- 14964651
TI  - Malaria status in Al-Hodeidah Governorate, Yemen: malariometric parasitic survey
      & chloroquine resistance P. falciparum local strain.
AB  - Malaria continues to be a major public health problem in Al-Hodeidah G. A cross
      sectional malariometic parasitic survey including 4000 Yemenis of various age
      /sex groups were enrolled in this study from 43 villages/or Harah in five
      selected districts representing Al-Hodeidah G. Duplicate thin and thick blood
      smears were stained with Giemsa's stain and examined. Out of 4000 examined
      slides, 646 (16.2%) were found to be malaria positive, 508 (78.6%) of them were
      detected through ACD, while 138 (21.4%) cases were detected by PCD. The overall
      parasite rate was 16.2%, a situation of prevalently mesoendemic condition. P.
      falciparum was the predominant species recorded (96.7%), followed by P. vivax
      (1.7%), the least prevalent was P. malariae (0.3%). Yemen has been considered
      free of ovale malaria. The recorded an indigenous case of P. ovale for the first
      time in Yemen should be taken into consideration for the existence of this
      particular Plasmodium species when surveying for malaria in the future. The
      present study was the first document in Yemen to compare simultaneously the in
      vivo and in vitro response to chloroquine among 209 of P. falciparum field
      isolate patients that were satisfied all criteria of WHO for the implementation
      of the in vivo and in vitro tests and were obtained by PCD and ACD methods.
      Chloroquine resistance of local strain of P. falciparum was recorded in all
      studied districts (Zabid, Bajil, Azohrah, Azaidiah and Al-Hodeidah city). RIII
      (high level of resistance) was recorded for the first time in Yemen and should be
      taken into consideration in the treatment of infected malaria patients. This
      calls for urgent revision of the current malaria treatment policy in Yemen where
      chloroquine is the first-line treatment of uncomplicated P. falciparum malaria.

PMID- 14964652
TI  - Experimental demonstration of hepatitis C virus (HCV) in an Egyptian strain of
      Culex pipiens complex.
AB  - Reverse transcriptase (RT) polymerase chain reaction (PCR) was used to detect
      hepatitis C Virus (HCV) RNA among heads, guts, larvae and eggs of Culex pipiens
      complex. The mosquitoes were trapped from homes of hepatitis C patients or among
      the same organs of symbiotic (normal gut bacteria) and aposymbiotic (without gut
      bacteria) mosquitoes fed HCV positive blood by an artificial membrane feeder. The
      eggs and larvae resulted from symbiotic females fed HCV positive blood was tested
      for HCV-RNA. Hepatitis C virus RNA was detected only in heads of symbiotic
      mosquitoes collected from homes of HCV positive patients at 3h and 6h after
      feeding. The virus was detected at 3d and 8d after being fed on HCV-RNA positive
      blood in guts of the same group. The virus was not detected in the eggs or larvae
      resulted from female mosquitoes fed on HCV-RNA positive blood. The results raise
      the possibility of the mechanical and/or biological transmission of HCV by Cx.
      pipiens, and pave the way to the ongoing study on the effect of gut bacteria of
      Cx. pipiens in a trial to identify an anti-HCV agent.

PMID- 14964653
TI  - Human infection with Onchocerca volvulus in Asir District (Saudi Arabia).
AB  - During one academic year, three patients were referred to Parasitology Laboratory
      from Dermatology Outpatients Clinics in King Abdulaziz University Hospitals. They
      were diagnosed as Sowda (chronic hyperactive form of onchocerciasis volvulus).
      The patients came from Asir Region in the Southern of the Kingdom. The lesion was
      characterized by a sever papule dermatitis localized to the lower limbs, with
      marked skin darkening. There was extensive follicular hyperplasia of the regional
      lymph nodes in two cases only. The skin snips taken from the three patients were
      positive microfilariae. On the other hand, the urine sample of one patient was
      positive. Six months after the onset of treatment by the clinicians in the
      Specialized Hospital, skin snips and urine samples were negative.

PMID- 14964654
TI  - Effect of some chemical agents on the viability of Cysticercus bovis.
AB  - The effect of eight chemicals; vinegar, Allium sativum (crude garlic), Acacia
      auriculiformis, lemon juice, praziquantel, pumpkin, perosan and yomesan on the
      viability of cysticerci of Taenia saginata in vitro was investigated. The minimum
      exposure time required for cysticerci to be non-evaginable for the eight
      chemicals were 5, 10, 25, 40, 55, 75, 90 and 105 minutes respectively. The best
      one was vinegar and the least effective was yomesan.

PMID- 14964655
TI  - Clinical, laboratory and ultrasonography features of proven human fascioliasis.
AB  - Examination of twenty parasitologically proven human cases of fascioliasis showed
      the following clinical, laboratory and ultrasonography results: (1) Both sexes
      are susceptible to fascioliasis. The smallest one was a child 3-year old. (2) The
      most important clinical manifestations are: a- abdominal distention and
      flatulence (30%), b- right upper quadrant pains (25%), colicky abdominal pains
      (25%), d- pallor (25%), and etympanitic abdomen (25%). Nevertheless, 15% of the
      patients showed no symptoms. (3) The most significant items in the CBC and liver
      function tests are: a- significantly high eosinophilia, b-high alkaline
      phosphatase, and c- low haemoglobin. Besides, two fascioliasis patients had high
      serum bilirubin. (4) Ultrasonography diagnosed only nine fascioliasis patients
      (45%). The result was critically discussed.

PMID- 14964656
TI  - Correlation between snails and fish in fish ponds of World Fish Center (ICLARM)
      with special reference to snail vectors of schistosomiasis and fascioliasis.
AB  - The abundance of snail species in earthen fish ponds, irrigation and drainage
      canals at World Fish Center (ICLARM) in descending order was Bellamya unicolor
      (50.89%) > Physa acuta (18.94%) > Cleopatra bulimoides (7.6%) > Lanistes
      carinatus (6.73%) > Bulinus truncatus (5.19%) > Melanoides tuberculata (4.83%) >
      Lymnaea natalensis (3.14%) > Gabbiella senaariensis (0.9%) > Biomphalaria
      alexandrina (0.55%) > Lym naea truncatula (0.4%) > Planorbis planorbis and
      Succinea cleopatra (0.33%) > Ferrissia isseli (0.18%). Dead snails constituted
      about 5.19% of all the collected specimens. There were dramatic decrease in the
      total number of pulmonates in fish ponds which contained only Tilapia sp., and a
      very small number of cat fish, whereas the numbers of prosobranchia snails were
      much higher in these ponds. In fish ponds which accommodated a variety of fish
      species, the most dominant snail was B. unicolor followed by L. carinatus.
      However, pulmonate snails were absent in these ponds. B. truncatus was the only
      snail species found in concrete tank which contained only young tilapias with a
      very small size (5-8 cm in standard length). In irrigation canals, the number of
      snails and diversity was much higher than those in fish ponds. Out of 191 snails
      collected from inlet irrigation canal, 71 were dead, but in the outside
      irrigation canals, seven out of 564 snails were dead. P. acuta was absent in all
      examined fish ponds, but it was alive and in a high number (497 snails) in the
      outside irrigation canals. The number of snails collected from Bahnasawy drain
      was remarkably low (128 snails), however the diversity of snails was much higher
      compared to those in fish ponds and irrigation canals. Snail populations were
      stable with constant recruitment of young to adult snails for all the studied
      species.

PMID- 14964657
TI  - Laboratory evaluation of Bacillus sphaericus recycling in mosquito larvae.
AB  - After ingestion by Culex pipiens and Anopheles pharoensis 4th instar larvae,
      spores of Bacillus sphaericus strain faiyoum rapidly germinated inside live
      mosquito midgut. Bacterial counts and electron microscopic observations on
      intoxicated larvae revealed that the number of viable spores rapidly decreased
      during the first 12 h, with a maximum between 12 and 24 h. In cadavers, the
      number of heat-resistant spores quickly increased between the first and second
      day post-feeding. After one week, the number of spores inside dead larvae reached
      approximately 20 times the number of ingested spores for both mosquito species (4
      x 16(5) spores/larva). Ultrathin sections of recycled spores showed the presence
      of a crystalline inclusion identical to that initially present in spores before
      ingestion. Bioassay on Cx pipiens 4th instar larvae showed a similar toxicity
      between in vivo recycled spores (LC50 = 1.1 +/- 0.3 x 10(5) spores/ml after 24h
      exposure) and culture-medium-grown spores of B. sphaericus strain faiyoum (LC50 =
      1.7 +/- 10(5) spores/ml).

PMID- 14964658
TI  - Treatment of Egyptian dicrocoeliasis in man and animals with Mirazid.
AB  - Two human cases with dicrocoeliasis dendriticum were successfully treated one
      with Praziquantel (25mg/kg 3 times daily after meals, for four successive days)
      and second with Mirazid (2 capsules of 300 mg. each, daily an hour before
      breakfast, for six successive days) as indicated clinically and
      parasitologically. On the other hand, one imported sheep and two locally bred
      goats naturally infected with D. dendriticum were successfully treated with Oleo
      resin solution (dose of 6 ml of 10 gm% equal to 2 Mirazid capsules before
      breakfast) per os once daily for four successive days. The animals were
      slaughtered on 5th day. Mirazid (capsule or Oleo-resin solution) was effective
      against dicrocoeliasis in man and animal respectively.

PMID- 14964659
TI  - Role of wheat germ agglutinin (WGA) in treatment of experimental
      cryptosporidiosis.
AB  - The therapeutic effect of wheat germ agglutinin (WGA) as a lectin molecule either
      alone or with Nitazoxanide (NTZ) was evaluated experimentally on cryptosporidial
      infection using immunosuppressed mice. A total of 100 suckling albino mice were
      immunosuppressed and infected with 106 purified Cryptosporidium oocysts. The
      oocyst count in stool using modified Ziehl Neelsen technique on the days post
      infection (p.i), the histopathological examination of ileum sections and the IFN
      Y serum level were assessed for the drug evaluation. The use of WGA alone or with
      NTZ showed significant reduction of excreted oocyst count started on day 7 (p.i)
      (p < 0.05) & (p < 0.01) respectively while the use of NTZ showed significant
      reduction (p < 0.05) started on day 10 (p.i) in comparison to control group. The
      combined therapy showed significant reduction (p < 0.01) in comparison to NTZ
      received group on days 7 and 10. The histopathological examination of mice
      received WGA alone or with NTZ showed increased inflammatory reaction and
      infiltrating inflammatory cells with multiple foci of enterocyte exfoliation
      along the villi. The IF N-Y serum level was significantly higher (p < 0.05) than
      control and NTZ received groups. In conclusior the combined therapy of NTZ and
      WGA showed earlier and better therapeutic effect against cryptosporidial
      infection. The results were critically discussed.

PMID- 14964660
TI  - Cross-reaction: a common trait among helminthes.
AB  - Cross-reaction between three important zoonotic helminths, Fasciola gigantica,
      Trichinella spiralis and Echinococcus granulosus, was proved by ELISA. Cross
      binding activities in the prepared antisera were strongly directed towards
      protoscolices and hydatid fluid antigens of E. granulosus rather than to F.
      gigantica and T. spiralis antigens. Two sets of polypeptides were identified in
      each antigen by immunoblot; species-specific and cross-reactive. Cross-reactive
      components in F. gigantica antigen were 205 KD, 178 KD, 166 KD, 106 KD, 100 KD,
      65 KD, 45 KD and 32 KD. While, cross-reactive molecules in T. spiralis antigen
      were 205 KD, 191 KD, 166 KD, 148 KD, 132 KD, and 32 KD. In protoscolices antigen
      six cross-reactive components were identified, 205 KD, 191 KD, 149 KD, 106 KD, 45
      and 32 KD. Moreover, 205 KD, 190 KD, 177 KD, 149 KD, 103 KD and 33 KD were
      detected in hydatid fluid antigen by heterologous antisera. Interestingly, three
      polypeptides of 205 KD, 149 KD and 32 KD showed broad immunogenicity with the
      developed antisera raising the prospect of being putative common
      immunoprophylactic components.

PMID- 14964661
TI  - Comparative immunodiagnostic approach of toxocariasis in buffalo calves.
AB  - Five Toxocara vitulorum antigens were utilized to diagnose natural toxocariasis
      in buffalo calves by ELISA. Adult antigen was proved to be the most potent one.
      The second potent antigen was egg antigen followed by excretory secretory antigen
      of male worms then female worms. The coproantigen was the least potent one. The
      electrophoretic make-up of the antigens, examined by SDS-PAGE, revealed different
      patterns of separation. Common as well as specific component(s) to each antigen
      were identified. Employing naturally infected buffalo calf sera in immunoblot
      assay, five immunogenic components were detected in adult antigen of molecular
      weight 191 KD, 166 KD, 102 KD, 65 KD and 54 KD. The reactive polypeptides in egg
      antigen were 191 KD, 105 KD, 99 KD and 79 KD. In coproantigen, six bands were
      identified. These components were of molecular weight 191 KD, 178 KD, 166 KD, 124
      KD, 96 KD and 65 KD. Five components of molecular weight 191 KD, 166 KD, 102 KD,
      96 KD and 65 KD were immunogenic in excretory/secretory antigen of male worms.
      Only four polypeptide of 191 KD, 166 KD, 102 KD and 66 KD were identified in
      excretory/secretory female antigen. Of interest is the immunogenic component of
      54 KD expressed only by adult extract in immunoblot assay. This component could
      be responsible for the immunodiagnostic advantage of adult worm antigen and it
      deserves further studies to evaluate its diagnostic value.

PMID- 14964662
TI  - Role of nitric oxide in host defense against Hymenolepis nana infection.
AB  - The defensive role of nitric oxide (NO) against Hymenolepis nana was investigated
      in vivo and in vitro studies. Serum NO levels were increased (P < 0.001) in mice
      5 days (cysticercoid stage) and 15 days (adult stage) after H. nana induced oral
      infection with 1000 eggs/mouse, compared with normal controls. Meanwhile, L-NAME,
      a NO synthase inhibitor, oral administration in drinking water to infected mice
      caused a non significant decrease in serum NO levels (P > 0.05) compared with
      normal controls, and was associated with a significant increase in number of both
      cysticercoids and adult worms (P < 0.001) compared to that in infected mice 5 and
      15 days post infection. In an in vitro study, the NO donor; sodium nitroprusside
      caused an increased mortality rate of H. nana cysticercoids and adult worms (P <
      0.001) compared with controls without NO donor, and this was in a concentration
      dependent manner (P < 0.001). Implications of these results are discussed.

PMID- 14964663
TI  - Erythrocytic and merogonic stages of Hepatozoon ridibundae sp. nov. infecting the
      Arabian ranid frogs, Rana ridibunda in Saudi Arabia with reflections on the
      haemogregarine complex.
AB  - The prevalence and levels of parasitaemia of haemogregarine infection among
      Arabian ranid frogs, Rana ridibunda, in Saudi Arabia was studied for the first
      time. Erythrocytic and merogonic stages of Hepatozoon ridibundae sp. nov. in the
      intermediate vertebrate host, R. ridibunda were described by light microscopy.
      The erythrocytic parasites were differentiated into small form (trophozoite)
      measuring 14.6 +/- 0.3 x 3.8 +/- 0.4 microm and the mature form (gamont) which
      was banana-shaped with hooked anterior end and blunt broad posterior end and
      measuring 19.8 +/- 1.8 x 5.2 +/- 0.6 microm. The gamonts of the present parasite
      induced nuclear fragmentation or segmentation in host erythrocytes. Merogony, of
      the ectomerogonic type, took place in the liver parenchyma cells. Two meront
      types were observed. Small meronts (micromeronts) yielded 2-6 (average 4) large
      merozoites (macromerozoites) measuring 16.6 +/- 0.6 x 6.2 +/- 0.5 microm in size.
      Large meronts (macromeronts) yielded 18-30 (average 24) elongated merozoites
      (micromerozoites) measuring 15.2 +/- 0.3 x 3.8 +/- 0.4 microm. A partial
      systematic revision of the haemogregarine complex was discussed in the view of
      the diagnostic characteristic features of the 6 recognized haemogregarine genera.

PMID- 14964664
TI  - Cytopathological action in mosquito larvae fed with Bacillus sphaericus (strain
      faiyoum) spore/crystal complex.
AB  - Ingestion of Bacillus sphaericus (strain faiyoum) spore/crystal complex by larvae
      of Anopheles pharoensis, Culex pipiens and Aedes caspius was rapidly followed by
      a dissolution of the protein crystalline inclusions inside the anterior stomach
      of the three species. During the first day of the, B. sphaericus spores
      germinated within the mid-gut lumen, and were in a vegetative stage between 36-48
      hours after ingestion when larvae began to die. Ultrastructural observations
      focused on larval mid-gut showed alterations, which differ according to the
      mosquito species, being localized mainly in the gastric caecae and posterior
      stomach. With the bacterial concentration used, neither general cell swelling nor
      complete breakdown of the mid-gut epithelium was recorded before larval death. In
      An. pharoensis larval mid-gut epithelium large low-electron-density areas
      appeared, rough endoplasmic reticula formed numerous concentrical structures and
      mitochondria swelled. Large vacuoles (of unknown origin) appear early in the Cx.
      pipiens mid-gut cells and rough endoplasmic reticula broke into small vesicles.
      Mid-gut epithelial cells of Ae. caspius showed mitochondria swelling except in
      the anterior stomach and a vacuolization of smooth reticula: these aspects
      remained unchanged until the larvae died.

PMID- 14964665
TI  - Occurrence of nematode larvae in terrestrial hermit crab Coenobita scaevola
      Forskal from Safaga region, Egypt.
AB  - The present work represents a new host, the terrestrial hermit crab, Coenobita
      scaevola Forskal and a new locality records for the larval nematode, Ascarophis
      from Safaga city. The results showed a direct relationship between host size
      (carapace length) and the prevalence rate of infected specimens. Larval nematodes
      were rarely found in specimens smaller than 17.0 mm in carapace length. Also, the
      fecundity of infected crabs was less than that of normal ones. Two types of host
      tissue response to infection were represented by muscular and haemocytic capsules
      around the larval nematodes.

PMID- 14964666
TI  - Further studies on autoclaved cercarial vaccine against schistosomiasis: safety,
      longevity and stability.
AB  - The autoclaved cercarial vaccine (ACV) which is a special type of killed vaccine
      has been reported to induce experimental high level of homologous protective
      immunity. This study was to adjust the dose and to assess vaccine safety,
      longevity and stability as well as the possibility of transplacental transmission
      of immune response from pregnant mice to their offspring. The results showed that
      two doses of the lowest most effective concentration of ACV that achieved the
      high percentage reduction of worm burden is safe as demonstrated by absence of
      any local or systemic side effects, normal blood picture and normal liver and
      kidney function tests. ACV is stable when kept either at 4 degrees C for six
      months or at -35 degrees C for up to 12 months and it offered considerable
      duration of longevity. Offspring of vaccinated mothers didn't show any signs of
      protection against challenge infection.

PMID- 14964667
TI  - Role of circulating Fasciola antigens and IgG4 isotype in assessment of cure from
      fascioliasis.
AB  - Sixty-eight individuals were included in this study, 30 of them presented with
      Fasciola infection, 20 were infected with other parasites but not Fasciola
      (infected control group) and 18 individuals were parasite-free (normal control
      group). For all groups, stool analysis by modified formol-ether technique and
      Kato thick smears for egg counts and the circulating Fasciola antigens (CFAgs)
      and anti- Fasciola IgG4 isotype were estimated by ELISA technique. Complete blood
      count, liver functions tests and abdominal ultra-sonography were performed for
      all Fasciola-infected patients. Patients with fascioliasis received a myrrh
      derived drug (Mirazid) in a dose of 10 mg/kg b.wt., one hour before breakfast for
      six consecutive days. Remeasuring of the above parameters was performed one and
      three months after therapy. Detection of CFAgs was found to be a useful marker
      for assessment of core. No cross reaction was observed between Fasciola and other
      parasites by using CFAg (100% specificity). The level of these antigens
      correlated positively with signs of cure; parasitologically, clinically or
      ultrasonographically. Detection of IgG4 isotype was found to be a more sensitive
      and accurate immunodignostic tool for fascioliasis, but it was not a useful
      marker for assessment of cure. Mirazid drug possesses high therapeutic efficacy
      (100% cure rate) on fascioliasis without remarkable side effects.

PMID- 14964668
TI  - Digenetic trematode of some aquatic birds from eastern province in Saudi Arabia.
AB  - 122 aquatic birds, 35 red shank (Tringa totanus), 24 common snip (Gallinago
      gallinago), 48 moorhen (Gallinula chloropus), 15 Teal (Anas crecca) trapped near
      the cost of Al- Qateef area in the eastern province, Saudi Arabia, were examined
      for helminth parasites. 35 birds (28.68%) were infected with one or more helminth
      parasites, 31 T. totanus (88.57%), 2 G. gallinago (8.33%), 2 A. crecca (13.33%)
      and none in C. chloropus. The isolated helminthes belong to six families and
      eight species. Bilharziellia polonica (22.86), Acanthoparyphum phoeincopteri
      (11.43), (8.33), (6.66) in different birds respectively, Himasthla rhigedana
      (14.3), Psilochasmus aglyptorchis (6.66), Knipowitschiatrema nico/ai (2.8),
      Spelophalls sp. (2.8) Diacetabulurn curviclon (42.9), Cyclocoelurn microstomum
      (5.7).

PMID- 14964669
TI  - The effects of myrrh (Commiphora molmol) on the infected snails of Schistosoma
      sp. and their egg masses: effect on shedding of cercariae and on snail fecundity.
AB  - Myrrh has molluscicidal effect on infected Bulinus truncatus and Biomphalaria
      alexandrina snails at low concentrations (10 & 20 ppm respectively) after 24
      hours exposure. The number of dead-snails increased with prolongation of exposure
      time. All Schistosoma free cercariae were killed by 2.5 ppm within 15 minutes.
      One day-old egg masses were more susceptible to the ovicidal effect of Myrrh than
      the five-day old ones. Both types of eggs were more resistant to the effect of
      Myrrh than the adult snails, embryogenesis began to stop at 20 ppm and eggs were
      all killed at 60 & 80 ppm. Shedding of cercariae of Schistosoma mansoni from
      infected B. alexandrina stopped at 1 ppm and was suppressed at 0.8 ppm. Snail
      fecundity decreased at 1 ppm.

PMID- 14964670
TI  - Immunological indicators of morbidity in human schistosomiasis mansoni: role of
      vascular endothelial growth factor and anti-soluble egg antigen IgG4 in disease
      progression.
AB  - Based sonographic examinations of 90 schistosomiasis mansoni, they were divided
      into five groups: lightly infected, heavily infected, intestinal, early
      hepatosplenic and periportal fibrosis. Using ELISA, the levels of circulating
      vascular endothelial growth factor (VEGF) and anti-soluble egg antigen (SEA) IgG4
      were measured in their sera. Compared to normal controls, VEGF levels were
      significantly raised in all schistosomiasis patients groups except lightly
      infected and intestinal patients were insignificantly elevated. The level of VEGF
      correlated with disease progression from lightly infected to periportal fibrosis
      patients. It also correlated with sonographic indicators of portal hypertension;
      presence of portosystemic collaterals, portal vein dilatation and splenomegaly.
      Serum IgG4 was significantly raised in only periportal fibrosis and portal
      hypertension patients. The results provided evidence that circulating levels of
      VEGF can serve as a new indicator of progression of schistosomiasis mansoni
      reflecting angiogenesis that regulates the granuloma and fibrosis development in
      liver while IgG4 seemed to be an indicator of only fibrosis development. Both are
      potential sensitive markers for effectiveness of treatment in periportal fibrosis
      patients. The understanding of the key role of VEGF in schistosomiasis mansoni
      pathogenesis may provide a new pharmacological target.

PMID- 14964671
TI  - The in vitro effect of Assafoetida on Trichomonas vaginalis.
AB  - Assafoetida is an oleo-gum resin obtained from the roots and stems of many Ferula
      species such as F. foetida Regel, F. asafoetida Linn, F. alliacea Boiss. and F.
      narthex Boiss, family Umbelliferae (carrot family), plants growing indigenously
      in Iran, Afghanistan and north of India. Assafoetida is commonly used as a
      flavoring agent in food and as a traditional medicine for many diseases in many
      parts of the world. In this work, the effect of Assafoetida on growth of
      Trichomonas vaginalis in vitro was studied and compared to metronidazole as a
      reference drug. It showed that Assafoetida had a potent antiparasitic effect on
      T. vaginalis compared to metronidazole, thus, worth further investigation to
      study its applicability in treatment of parasitic infections.

PMID- 14964672
TI  - Nematodes and water pollution in eastern part of Nile Delta.
AB  - Examination of some represented water sites revealed presence larvae and eggs of
      the nematodes infecting man and animals. Eggs in a descending order of abundance
      were Trichostrongylus, Toxocara canis, T. vitolorum, and Ascaris sp., then
      Trichocephalus and Ancylostoma sp. Larvae in a descending order were
      Strongyloides, Trichostrongylus and Ancylostoma sp. No doubt contaminated or
      polluted water plays an important role as nematode-borne source.

PMID- 14964673
TI  - Co-agglutination (Co-A): a rapid test for the diagnosis of experimental
      trichinellosis.
AB  - Co-agglutination test (Co-A test) which has a wide application spectrum in
      bacterial diseases has been used for the detection of some parasitic infections.
      This work was to evaluate Co-A test as a new diagnostic tool in detection of T.
      spiralis antigens in both sera and urine of experimentally infected mice as
      compared with ELISA, for the diagnosis of trichinellosis. The results obtained by
      Co-A test were closely correlated with those of ELISA. The most important was
      that both tests were capable to detect T. spiralis antigen in urine of light and
      heavily infected mice only at the 30th days post infection. So, Co-A is an
      accurate, easy and rapid test that can be used on large scales for diagnosis of
      trichinellosis.

PMID- 14964674
TI  - Rattus rattus: a new host for fascioliasis.

PMID- 14964675
TI  - Adhesion--the solution to all problems?

PMID- 14964676
TI  - Factors contributing to the incompatibility between simplified-step adhesives and
      self-cured or dual-cured composites. Part II. Single-bottle, total-etch adhesive.
AB  - PURPOSE: As adhesives containing hydrophilic/acidic resin components are
      vulnerable to water movement after polymerization, this study tested the
      hypothesis that coupling of a single-bottle adhesive (OptiBond Solo Plus) to
      self/dual-cured composites is compromised by adhesive permeability, even with the
      adjunctive use of chemical co-initiators. MATERIALS AND METHODS: Two versions of
      chemical co-initiators (activators) were investigated: the proprietary resin
      containing OptiBond Solo Plus Activator (A), and a resin-free solution of 2%
      benzene sulphinic acid sodium salt in ethanol (B). For microtensile bond testing,
      hydrated (H) or dehydrated (D) bonded human dentin were coupled to a dual-cured
      composite (Bis-Core) under light- (L) or self-activation (C) mode. A delayed
      light-activation mode (DL) was also employed to simulate the slower rate of
      polymerization of self-cured composites but without the influence from adverse
      chemical interaction. Nine groups were tested: 1) L-H (control); 2) DL-H; 3) DL
      D; 4) C-H; 5) C-D; 6) CA-H; 7) CA-D; 8) CB-H; and 9) CB-D. For transmission
      electron microscopy, a light-cured and an experimental self-cured composite of
      the same composition were used for the nine groups. RESULTS: Only the bond
      strength results of the experimental groups DL-D (Group 3) and CB-D (Group 9)
      were not significantly different from the control group L-H (p > 0.05). TEM
      revealed the presence of discrete silver-filled water blisters along the adhesive
      composite interface in groups 2, 6, and 8, and within the composite in group 4.
      Adverse chemical interaction in groups 4 and 5 resulted in the observation of a
      line of silver deposits along the adhesive composite interface. CONCLUSION: The
      coupling of composites after prolonged contact with hydrated dentin bonded with
      OptiBond Solo Plus is affected by the intrinsic permeability of the adhesive. The
      adjunctive use of the Activator is only slightly effective in improving the
      coupling of this adhesive with self/dual-cured composites. Although the use of
      resin-free benzene sulphinic acid sodium salt solution completely eliminates the
      adverse chemical interaction, the inherent permeability of the polymerized
      adhesive precludes optimal coupling of self/dual-cured composites to bonded
      hydrated dentin.

PMID- 14964677
TI  - Effect of acid-etching on the enamel bond of two self-etching systems.
AB  - PURPOSE: To evaluate enamel bond strengths of self-etching primer systems with
      and without the use of phosphoric acid etching. MATERIALS AND METHODS: The enamel
      of sixteen bovine incisors was ground with wet 600-grit SiC paper, and specimens
      were divided into seven groups. Group SE and group ABF were bonded with Clearfil
      SE Bond (Kuraray) and an experimental self-etching primer system ABF (Kuraray) in
      accordance with the manufacturer's instructions. The enamel of groups SE+AC and
      ABF+AC was acid-etched (AC) prior to application of the primers. The enamel of
      groups AC+SE-P and AC+ABF-P was acid-etched and the bonding resin was applied
      without primer. All of these groups were restored with Clearfil AP-X (Kuraray).
      For the control group (SB), enamel was etched and bonded with Single Bond (3M)
      according to manufacturer's instructions and restored with Z-250 (3M). After 24 h
      of water storage, the teeth were sectioned into 0.7-mm-thick slabs, trimmed for
      microtensile bond testing and subjected to tensile forces at a cross-head speed
      of 1 mm/min. After testing, all samples were analyzed with SEM. Data were
      evaluated by one-way ANOVA and Fisher's PLSD (alpha = 0.05). RESULTS: Acid
      etching prior to application of the self-etching primer produced higher bond
      strengths to enamel than self-etching priming only. Omission of the primer step
      provided bond strengths similar to the other acid-etched groups. SEM analysis
      revealed that when the acid was applied prior to the self-etching primers, an
      increase in failure within enamel occurred. CONCLUSION: Since high bond strength
      to enamel is critical for good margins and seal of the restorations, applying the
      etching step should be considered in case of restorations that rely mainly on
      enamel bonding.

PMID- 14964678
TI  - Adhesion of 4-META/MMA-TBB resin to ground enamel treated with self-etching
      primer containing amino acid methacrylate.
AB  - PURPOSE: The effect of self-etching primer on the adhesion of tri-n-butylborane
      (TBB)-initiated resin to enamel has not been fully determined. We prepared a self
      etching primer containing amino acid methacrylate, and evaluated the
      effectiveness of the self-etching primer for the adhesion of TBB-initiated 4
      methacryloxyethyl trimellitate anhydride (4-META)/methyl methacrylate (MMA) resin
      to ground enamel. MATERIALS AND METHODS: Methacryloyloxy tyrosine (MTY) was
      prepared by reacting methacryloyl chloride and L-tyrosine in trifluoroacetic
      acid. An original self-etching primer containing an aqueous mixture of MTY, 35
      wt% 2-hydroxyethyl methacrylate (HEMA), and 3 wt% ferric chloride was designed.
      Three strengths of MTY (5%, 10%, and 20%) were tested. The bovine enamel surface
      was treated with the self-etching primer for 30 s. After drying, a stainless
      steel rod was bonded to the enamel using TBB-initiated 4-META/MMA resin. The
      tensile bond strength was measured after 1-day immersion in water at 37 degrees
      C. RESULTS: The self-etching primer containing 20 wt% MTY (20MTY) yielded a
      significantly higher bond strength of 13.2 +/- 2.8 MPa than the self-etching
      primer containing 5 wt% and 10 wt% MTY. This value was not significantly
      different from that with phosphoric acid etching. Field-emission scanning
      electron microscopy revealed that 20MTY treatment produced no distinct
      dissolution pattern on enamel. Tight bonding between the resin and enamel was
      clearly observed. CONCLUSION: Our original self-etching primer containing 20 wt%
      MTY, 35 wt% HEMA, and 3 wt% ferric chloride was effective for obtaining strong
      adhesion of 4-META/MMA-TBB resin to enamel compatible with phosphoric acid
      etching.

PMID- 14964679
TI  - Microtensile dentin bond strength of self-etching and single-bottle adhesive
      systems in different cavity configurations.
AB  - PURPOSE: To evaluate the bond strength of a self-etching (Clearfil SE Bond) and a
      single-bottle (Excite) adhesive system using two cavity configurations (C-factors
      5 and 1). MATERIALS AND METHODS: Class I cavities (3 x 4 x 2.5 mm) were prepared
      in 28 extracted human molars using diamond burs under water cooling. Teeth were
      divided into 4 groups: G1: Excite, C-factor 5; G2: Excite, C-factor 1; G3:
      Clearfil, C-factor 5; G4: Clearfil, C-factor 1. To determine C-factor 5, systems
      were applied to all cavity walls according to the manufacturers' instructions (5
      bonded, 1 unbonded). For C-factor 1, lateral walls were isolated using nail
      varnish, and adhesive systems were only applied to the pulpal floor (5 unbonded,
      1 bonded). Cavities were restored using Tetric Ceram composite resin
      (Ivoclar/Vivadent), and bulk light cured for 40 s (500 mW/cm2). Teeth were stored
      in distilled water for 24 h at 37 degrees C, and then sectioned using a diamond
      disk, yielding stick-shaped specimens with a bonded area of approximately 0.8
      mm2. Specimens were submitted to the microtensile bond test at a rate of 1 mm/min
      speed in a universal testing machine. RESULTS: Resin-dentin bond strengths (MPa)
      were submitted to ANOVA and Tukey's tests (p < 0.05) [number of specimens]: G1 =
      35.8b [43]; G2 = 48.9a [55]; G3 = 45.9a [60]; G4 = 49.0a [53]. There was no
      statistically significant difference between adhesive systems for C-factor 1. For
      C-factor 5, Clearfil SE Bond produced higher values when compared to the other
      group. CONCLUSION: Changes in C-factor only affected the total-etch adhesive
      system tested. This may be a result of the different filler volume in the self
      etching system, and not of the bonding technique itself.

PMID- 14964680
TI  - Effect of 2% chlorhexidine on microtensile bond strength of composite to dentin.
AB  - PURPOSE: To evaluate the effect of 2% chlorhexidine on the microtensile bond
      strength of composite resin to dentin treated with three dentin bonding systems.
      MATERIALS AND METHODS: Flat dentinal surfaces were prepared in 24 extracted human
      third molars. Teeth were randomly divided into 8 distinct experimental groups
      according to the adhesive applied (Prime & Bond NT, Single Bond and Clearfil SE
      Bond), the application (yes/no) of chlorhexidine, and the time point at which it
      was applied (before or after acid etching the dentin). Composite resin blocks
      were built up over treated surfaces, and teeth were then stored in water at 37
      degrees C for 24 h. Samples were thermocycled, stored under the same conditions,
      and then vertically sectioned, thus obtaining specimens with 1.0 +/- 0.1 mm2
      cross-sectional area. Specimens were stressed in tension at 0.5 mm/min crosshead
      speed. Bond strength results were evaluated using a one-way ANOVA (p < 0.05). The
      modes of failures were verified using optical microscopy. Dentin disks were
      obtained from 3 additional teeth treated in the same manner for observation under
      SEM. The most representative samples of fractured specimens were also observed
      under SEM. RESULTS: No statistically significant differences of bond strength
      values were found between any groups. Failures occurred mainly within the bond;
      exclusively adhesive fractures (adhesive-dentin) were not observed. CONCLUSION:
      The 2% chlorhexidine solution, applied before or after acid etching of the
      dentin, did not interfere with the microtensile bond strength of composite resin
      to the dentin treated with Prime & Bond NT, Single Bond, or Clearfil SE Bond
      bonding systems.

PMID- 14964681
TI  - Experimental comparison of cavity sealing ability of five dental adhesive systems
      after thermocycling.
AB  - PURPOSE: To evaluate the cavity sealing obtained after thermocycling with five
      adhesive systems in which one all-in-one adhesive was compared to three one
      bottle adhesives, and to observe the effect of a low-charged resin layer added to
      a one-bottle adhesive. MATERIALS AND METHODS: Twenty-five recently extracted
      teeth were randomly allocated to five experimental adhesive systems (n = 5 each):
      Optibond Solo (OS), Scotchbond 1 (SB1), PQ 1, Prompt-L-Pop (PLP), SB1+Revolution
      (R). On each tooth, two rectangular cavities at the cementoenamel junction were
      filled with a microhybrid composite (Z100) and the tested adhesives. Teeth were
      thermocycled and stained with AgNO3 + vitamin C. Leakage was evaluated on a 6
      point (0-5) severity scale and the highest score was selected for each
      restoration. Results were treated by ordinal logistic regression and considered
      to be significant at p < 0.05. RESULTS: No significant difference was found
      between leakage values for enamel and dentin interfaces. Leakage scores never
      exceeded 2 for OS, SB1 and SB1+R, while they reached a maximum of 5 in 20% of PLP
      cases. OS was significantly better than the other adhesive systems, which were
      statistically equivalent. The addition of a flowable composite layer on SB1 did
      not yield a significant difference, but tended to give better results mainly at
      the dentin interface. CONCLUSION: The all-in-one adhesive PLP, because of quite
      variable results, seems less reliable than the one-bottle adhesives, of which OS
      provides significantly the best results. Addition of a flowable composite on SB1
      appears to yield slightly better results.

PMID- 14964682
TI  - Microleakeage and resin cement film thickness of luted all-ceramic and gold
      electroformed porcelain-fused-to-metal crowns.
AB  - PURPOSE: The purpose of this study was to evaluate the sealing ability of single
      unit all-ceramic and gold-electroformed crowns luted with a resin cement under
      laboratory conditions. MATERIALS AND METHODS: Thirty extracted maxillary
      premolars were selected. Standardized abutments were prepared for full-crown
      restorations with cervical margins located 1 mm below the cementoenamel junction.
      Samples were divided into two groups (n = 15) based on type of restorative
      system: Group 1: a heat-pressed all-ceramic system (IPS Empress 2, Ivoclar
      Vivadent); Group 2: a gold-electroformed porcelain-fused-to-metal system (Gramm
      Technik). Crowns were luted with Excite DSC bonding system (Ivoclar-Vivadent) and
      Variolink II resin cement (Ivoclar-Vivadent) following manufacturer's
      instructions. After luting procedures and 700 thermal cycles (5 degrees C and 55
      degrees C, 1 min dwell time), 20 specimens (n = 10 per group) were randomly
      selected and processed for microleakage evaluation at cervical sites. The
      remaining specimens (n = 5 per group) were prepared for SEM investigation on film
      thickness. Microleakage and film thickness data were statistically evaluated
      using the Mann-Whitney U-test (p < 0.05). RESULTS: Fifty percent of group 1 and
      60% of group 2 samples showed leakage. For group 1, dye penetration was mostly
      observed between metal and resin material, while group 2 specimens showed leakage
      mainly between ceramic margins and resin cement. Samples from group 1 showed a
      cement thickness of 82 microm, while 71 microm was found for group 2.
      Statistically significant differences were not found between samples from the two
      groups. CONCLUSION: Regarding microleakage and film thickness, both restorative
      systems evaluated in this study performed similarly.

PMID- 14964683
TI  - Bond strength of resin cement to dentin and to surface-treated posts of titanium
      alloy, glass fiber, and zirconia.
AB  - PURPOSE: To determine the effect of surface treatments on bond strength of two
      resin cements (ParaPost Cement and Panavia F) to posts of titanium alloy
      (ParaPost XH), glass fiber (ParaPost Fiber White), and zirconia (Cerapost), and
      to dentin. MATERIALS AND METHODS: After embedding, planar surfaces of posts (n =
      9 to 14) and human dentin (n = 10) were obtained by grinding. The posts received
      one of three surface treatments: 1. roughening (sandblasting, hydrofluoric acid
      etching), 2. application of primer (Alloy Primer, Metalprimer II, silane), or 3.
      roughening followed by application of primer (sandblasting or etching followed by
      primer, Cojet treatment). ParaPost Cement and Panavia F were bonded to the post
      and dentin specimens, and the bonded specimens were placed in water at 37 degrees
      C for 7 days. The specimens were debonded in shear. RESULTS: Panavia F had
      significantly higher bond strength to ground ParaPost XH, Cerapost, and dentin
      than did ParaPost Cement. Most surface treatments resulted in an improved bond
      strength of resin cements to the posts. Compared to the ground control, Cojet
      treatment and sandblasting were the most effective treatments. Etching of
      Cerapost with hydrofluoric acid with and without silane treatment significantly
      decreased the bond strength of Panavia F to the post. CONCLUSION: The bond
      strength of resin cements to the posts was affected by the material of the post,
      the surface treatment of the post, and by the type of resin cement. The bond
      strength of resin cement to dentin was influenced by the type of resin cement.

PMID- 14964684
TI  - Distribution of calcium-binding proteins in the cerebellum.
AB  - Calcium plays a fundamental role in the cell as second messenger and is
      principally regulated by calcium-binding proteins. Although these proteins share
      in common their ability to bind calcium, they belong to different subfamilies.
      They present, in general, specific developmental and distribution patterns. Most
      Purkinje cells express the fast and slow calcium buffer proteins calbindin-D28k
      and parvalbumin, whereas basket, stellate and Golgi cells the slow buffer
      parvalbumin only. They are, almost all, calretinin negative. Granule, Lugaro and
      unipolar brush cells present an opposite immunoreactivity profile, most of them
      being calretinin positive while lacking calbindin-D28k and parvalbumin. The
      developmental pattern of appearance of these proteins seems to follow the
      maturation of neurons. Calbindin-D28k appears early, shortly after cessation of
      mitosis when neurons become ready to start migration and differentiation while
      parvalbumin is expressed later in parallel with an increase in neuronal activity.
      The other proteins are generally detected later. During development, some of
      these proteins, like calretinin, are transiently expressed in specific cellular
      subpopulations. The function of these proteins is not fully understood, although
      strong evidence supports a prominent role in physiological settings with altered
      calcium concentrations. These proteins regulate and are regulated by
      intracellular calcium level. For example, they may directly or indirectly enable
      sensitization or desensitization of calcium channels, and may further block
      calcium entry into the cells, like the calcium-sensor proteins, that have been
      shown to be potent and specific modulators of ion channels, which may allow for
      feedback control of current function and hence signaling. The absence of calcium
      buffer proteins results in marked abnormalities in cell firing; with alterations
      in simple and complex spikes or transformation of depressing synapses into
      facilitating synapses. Calcium-binding protein implication in resistance to
      degeneration is still a controversial issue. Neurons rich in calcium-binding
      proteins, especially calbindin-D28k and parvalbumin, seem to be relatively
      resistant to degeneration in a variety of acute and chronic disorders. However
      other data support that an absence of calcium-binding proteins may also have a
      neuroprotective effect. It is not unlikely that neurons may face a dual action
      mechanism where a decrease in calcium-binding proteins has a first short-term
      beneficial effect while it becomes detrimental for the cell over the long term.

PMID- 14964685
TI  - Cerebellar connections: hypothalamus.
AB  - Morphological studies have described reciprocal cerebello-hypothalamic
      projections in various species. These connections provide evidence for the key
      role of the cerebellum and hypothalamus in physiological regulatory processes
      such as autonomic and endocrine homeostasis. Our recent study using horseradish
      peroxidase (HRP) retrograde axonal transport technique showed cerebellar
      connections with the posterior and the dorsomedial hypothalamic nuclei. Further,
      we have demonstrated regional differences of the connections of the dorsomedial
      hypothalamic nucleus in rat. The results of HRP labelling showed that afferent
      pathways originating from the anterior and posterior parts of dorsomedial
      hypothalamic nucleus indicate a number of differences in the projections. The
      posterior part of the dorsomedial hypothalamic nucleus and the posterior
      hypothalamic nucleus receives direct distinct projections from the cerebellum,
      whereas the anterior part of the dorsomedial hypothalamic nucleus does not.
      Moreover, the posterior part of the dorsomedial nucleus of the hypothalamus when
      compared to the posterior hypothalamic nucleus has more intense connections with
      the cerebellum. These observations bring a new perspective on the question of how
      the cerebellum is involved in the regulation visceromotor functions.

PMID- 14964686
TI  - In vitro cultured neurons for molecular studies correlating apoptosis with events
      related to Alzheimer disease.
AB  - This short review analyses the possible molecular events linking a general
      program of death such as apoptosis to highly specific intracellular pathways
      involving the function and degradation of two proteins--tau and amyloid precursor
      protein--which in their aggregated state constitute the hallmark of Alzheimer
      disease. By surveying the recent studies carried out in 'in vitro' neuronal
      cultures--with special emphasis to cerebellar granule neurons--the apparent
      correlation between onset of apoptosis, tau cleavage with formation of potential
      toxic fragments, and activation of an amyloidogenic route are discussed. Within
      this framework, proteasomes seem to play a crucial role upstream of the
      proteolytic cascade involving calpain(s) and caspase(s) by contributing to tau
      and amyloid precursor protein-altered breakdown and consequent tendency to
      aggregation of their degradation fragments. Thus, apoptotic death due to altered
      supply of anti apoptotic agents, neurotrophic factors, deafferentiation or other
      causes, may constitute a major trigger of the onset of Alzheimer disease.

PMID- 14964687
TI  - Current perspectives on the role of thyroid hormone in growth and development of
      cerebellum.
AB  - The thyroid hormone (TH) is essential for growth and development of brain,
      including the cerebellum. Deficiency of TH during the perinatal period results in
      abnormal cerebellar development, which is well documented in rodent animal
      models. TH exerts its major effect by binding to the nuclear TH receptor (TR), a
      ligand-regulated transcription factor. Although TR is highly expressed in many
      brain regions, including the cerebellum, TH-target genes that likely play
      critical roles in brain development have not yet been fully clarified. At
      present, however, expression of many cerebellar genes is known to be altered by
      perinatal hypothyroidism. Interestingly, after the critical period of TH action
      (first 2 weeks of postnatal life in rodent cerebellum), the activities of many
      genes that are altered by perinatal hypothyroidism return to the same levels as
      those of euthyroid animal despite morphological alterations. Several prominent
      candidate genes that may play key roles in TH-mediated cerebellar development are
      discussed in this review. On the other hand, TR-mediated transcription may be
      modulated by various substances. The nuclear hormone receptor superfamily
      contains more than 40 transcriptional factors and, most of these receptors are
      present in the brain. Possible interactions between TR and such transcription
      factors are also discussed. Further, several additional issues that need to be
      clarified are discussed. One such issue is the discrepancy of phenotypes among TR
      knockout and perinatal hypothyroid mice. Recent studies have provided several
      important clues to address this issue. Another current area that needs attention
      is the effect of endocrine disruptors on brain development. Since the molecular
      structures of TH and several endocrine disrupting chemicals are similar, the
      effect of such chemicals on brain may be exerted at least in part through the TH
      system. Recent studies have shown the possible interaction between TR and such
      chemicals. Overall, this review provides current findings regarding molecular
      mechanisms on TH action in cerebellar development.

PMID- 14964688
TI  - Unraveling the cerebellar cortex: cytology and cellular physiology of large-sized
      interneurons in the granular layer.
AB  - Neuronal network behaviors emerge from complex interactions between excitatory
      relay cells, principal cells and inhibitory interneurons. Therefore,
      characterizing homogeneous cell types and their properties is an essential step
      towards understanding information processing in the brain. The cerebellar cortex
      is generally described as a repetitive circuit composed of only five cell types.
      However, recent studies have revealed an unexpected diversity in the
      morphological, neurochemical and electrophysiological properties of the large
      sized granular layer interneurons. These data are reviewed here with an emphasis
      on the synaptic interactions of the different cell types within the cerebellar
      cortex. The existence of a complex network of excitatory and inhibitory
      interneurons controlling the spatial and temporal pattern of granule cell firing
      is documented, providing insights into the cellular and synaptic processes
      underlying oscillations and synchronization in the cerebellar cortex.

PMID- 14964690
TI  - Anp32e (Cpd1) and related protein phosphatase 2 inhibitors.
AB  - Mouse Anp32e (Acidic leucine-rich nuclear phosphoprotein 32 family, member e:
      NM_023210, P97822, formerly Cpd1), a protein identified in postnatal cerebellum
      by differential display, belongs to the superfamily of leucine rich repeat (LRR)
      proteins and to the Acidic Nuclear Phosphoprotein 32 (ANP32) family of protein
      phosphatase 2 (PPP2, formerly PP2A) inhibitors. Two families of PPP2 inhibitor
      proteins have been described, ANP32 and SET, represented by the human proteins
      ANP32A (NM_006305, formerly LANP, PP32, I1PPP2, PHAPI, MAPM, mapmodulin) and SET
      (NM_003011, formerly PHAPII, 2PPP2, I2PPP2, TAF-1BETA). Besides their common PPP2
      inhibitor activity, described several years ago, these nucleo-cytoplasmic
      shuttling phosphoproteins have additional and very important functions recently
      reported. In HeLa cells, ANP32A, SET (isoforms A and B) and ANP32B (APRIL), form
      a multi-subunit heterocomplex with ELAVL1 (NM_001419, formerly HuR), a protein
      that stabilizes short-lived mRNAs containing AU-rich elements (AREs). A similar
      heterocomplex, formed by SET (A and B) and ANP32A as major subunits, possess
      histone acetyltransferase inhibitory activity (INHAT), and have a role in
      chromatin remodeling and transcriptional regulation (histone code). The possible
      roles of these multifunctional proteins are discussed here, with emphasis on
      mouse Anp32e and the cerebellar tissue.

PMID- 14964689
TI  - The effects of cerebellar damage on maze learning in animals.
AB  - The role of the cerebellum in spatial learning has recently been investigated in
      genetically and non-genetically lesioned animal models, particularly in water
      mazes, in view of the minimal impact such lesions exert on swimming movements. A
      dissociation between place and cued learning in the Morris water maze has been
      observed in several models, including cerebellar mutant mice (Rora(sg), Nna1(pcd
      1J), nervous), rats with lesions of either the lateral cerebellar cortex or the
      dentate nucleus, and rats with selective Purkinje cell loss caused by
      intracerebroventricular injections of OX-7-saporin, confirming the hypothesis
      that cerebellar damage may cause a cognitive deficit independently of fine motor
      control. In addition, the results of hemicerebellectomized rats indicate the
      probable involvement of the cerebellum in working memory and the procedural
      aspect of maze learning. The findings of impaired maze learning in cerebellar
      lesioned mice and rats are concordant with those of deficient visuospatial
      functions in patients with cerebellar atrophy. The spatial deficits may be
      ascribed to altered metabolic activity in cerebellar-related pathways.

PMID- 14964691
TI  - Relationships between God and people in the Bible, Part II: The New Testament,
      with comparisons with the Torah.
AB  - IN AN EARLIER study on the first five books of the Bible, the Torah or
      Pentateuch, relationships between God and people were assessed with the use of a
      clinical-quantitative method, the core conflictual relationship theme (CCRT)
      method. Here, the study is extended to God or Jesus's relationships with people
      in the New Testament, to obtain the first description of those relationships
      based on an established measure of relationships. In the New Testament, many
      different kinds of relationship themes were observed, with benevolent and
      positive themes as the most frequent. Other results included that: (a)
      relationships in the New Testament often appeared more positive than in the
      Torah; (b) New Testament relationships between Jesus and people were less
      positive than between God and people; and (c) God's relationship with Jesus was
      more positive than God's relationship with Moses. Relationships with Paul, Peter,
      and women were also assessed. Relationship patterns were considered within the
      context of attachment theory, and biblical CCRT patterns were consistent with
      depiction of both secure and anxious attachments. Biblical relationships portray
      a variety of models for interpersonal relationships, ranging from the very
      positive to the very negative.

PMID- 14964692
TI  - Self-reported stress and the deficit syndrome of schizophrenia.
AB  - GENERALLY speaking, schizophrenia is not associated with diminished positive and
      negative emotions. Even patients with negative symptoms such as blunted affect
      have generally not differed in their levels of self-reported emotionality
      compared to patients without negative symptoms. However, there is evidence to
      suggest that a subgroup of patients with negative symptoms, those with the
      deficit syndrome, have a diminished capacity to experience positive and negative
      emotions. The present study examined whether ratings of the deficit and negative
      syndrome were associated with lower levels of self-reported stress during a
      laboratory-based, emotion-induction manipulation. Thirty-six participants with
      schizophrenia were asked to produce separate affectively positive and affectively
      negative narratives. Immediately following each narrative, participants were
      asked to report the level of stress they had experienced while recounting their
      memories. The deficit syndrome ratings, analyzed in a continuous and a
      categorical manner, were associated with lower levels of self-reported stress in
      the affectively negative condition. Moreover, the deficit and negative syndrome
      ratings significantly differed in their associations to levels of self-reported
      stress during both tasks, supporting the notion that there are appreciable
      differences between the two syndromes. Given that stress has been an essential
      component in conceptualizations of schizophrenia onset and relapse, the
      possibility of stress-resistant properties associated with the deficit syndrome
      should be tested in future research.

PMID- 14964693
TI  - Antidepressant exposure in bipolar children.
AB  - BIPOLAR disorder is increasingly diagnosed in children and adolescents. Given
      that antidepressants may precipitate mania, and with increased use of
      antidepressants in youths, it is reasonable to ask whether antidepressant
      administration might play a role in inducing earlier manic episodes. We reviewed
      all consecutive admissions with a diagnosis of bipolar disorder to a university
      affiliated children's hospital, and collected information regarding previous
      exposure to antidepressants and stimulants. The mean age of diagnosis of bipolar
      disorder in our cohort was 12 +/- SD 3.47 years. Children who received prior
      antidepressant and/or stimulant treatments had an earlier bipolar diagnosis (10.7
      +/- 3.05 years) than children never exposed to these medications (12.7 +/- 4.3
      years; one-tailed t = -1.33, df = 22, p = .099, power = .93). Stimulants appeared
      to be tolerated for a longer duration than antidepressants (55.5 +/- 20.42 months
      vs. 6.7 +/- 8.22 months, t = 6.6, df =12, p = .0001). Despite methodological
      imperfections, results indicate that children exposed to antidepressants appear
      to be diagnosed with bipolar disorder earlier than those never exposed to these
      medications. Although far from conclusive, these data are consistent with the
      hypothesis that antidepressant treatment is associated with a manic episode
      earlier than might occur spontaneously.

PMID- 14964694
TI  - A cry from the darkness: women with severe mental illness in India reveal their
      experiences with sexual coercion.
AB  - THIS STUDY used qualitative research methods to investigate the problem of sexual
      coercion among female psychiatric patients in India. Consecutive female
      admissions (n = 146) to the inpatient unit of a psychiatric hospital in southern
      India were screened regarding coercive sexual experiences. Women who reported
      coercion (n = 50; 34%) participated in a semi-structured interview to learn more
      about their experiences. Among these women, 24 (48%) reported that the
      perpetrator was their spouse, 13 (26%) identified a friend or acquaintance, and
      10 (20%) identified a relative such as an uncle or cousin. Most experiences
      occurred in the women's homes. Thirty of the 50 coerced women (60%) reported that
      they had not disclosed their experience to anyone, and that they had not sought
      help. Women revealed a sense of helplessness, fear, and secrecy related to their
      experiences. The problem of sexual coercion is seldom addressed in mental health
      care in India; the prevalence and severity of such experiences warrant immediate
      clinical attention and continued research.

PMID- 14964695
TI  - Outpatient psychotherapy for mothers--first empirical results.
AB  - MOTHERHOOD is a vulnerable phase in the life of any woman, one that may be
      associated with an increased risk of mental illness. Despite the major clinical
      significance of this patient group, only a few psychotherapeutic treatment
      programs are tailored to the needs of mothers of infants. Even when treatment is
      urgently needed, many mothers of infants reject inpatient psychotherapy so as not
      to be separated from their children. The outcome may be chronification of
      disorders, in some cases with a negative impact on their children's development.
      A new psychotherapeutic outpatient treatment program adapted to the special needs
      of mothers and offering a substitute to inpatient treatment is presented. First
      empirical results show that the presented treatment concept led to significant
      improvements in the symptoms, whose stabilization continued up to the follow-up
      two years after the start of therapy.

PMID- 14964696
TI  - Psychiatric and sociotherapeutic perspectives on the difficult-to-treat patient.
AB  - IN SPITE of substantial advances in the effective treatment of psychiatric
      illness, there is a growing perception among clinicians that those patients who
      present for inpatient care are more difficult to treat. The authors review the
      history of contributions about the patient who is difficult to treat and propose
      a new typology for characterizing acute, severe and complex dimensions of this
      cohort. They hypothesize first that patient difficulty cannot be conceptualized
      independently from the treatment context; and second, that treatment complexity
      leads to a specific strain between the on- and off-floor treatment staff, thus
      enhancing the perception of difficulty. Finally, the authors suggest innovations
      in the structure of the treatment environment that may facilitate treatment of
      these patients. These innovations operate especially in the area of reducing
      interstaff tensions and helping patients use rather than resist that treatment.

PMID- 14964697
TI  - Treatment of agitation using Depakote: a patient with dementia.

PMID- 14964698
TI  - Politics and psychopathology in an Arab-Israeli patient.

PMID- 14964699
TI  - Clean thoughts about dirty genes.
AB  - The mouse has joined the fruit fly, bread mold, and cyanobacteria as a tractable
      genetic system for studying mechanisms of circadian rhythms. The circadian
      rhythms of "knock-out" mice for specific clock genes, however, have demonstrated
      significant variability between laboratories. In this brief review, the authors
      discuss possible sources of this variability, focusing particularly on questions
      of modifier loci of circadian rhythms that vary between inbred mouse strains.
      They conclude with a short list of recommendations for researchers working on
      circadian rhythms in mixed-strain mice.

PMID- 14964700
TI  - Circadian synchronization and rhythmicity in larval photoperception-defective
      mutants of Drosophila.
AB  - A single light episode during the first larval stage can set the phase of adult
      Drosophila activity rhythms, showing that a light-sensitive circadian clock is
      functional in larvae and is capable of keeping time throughout development. These
      behavioral data are supported by the finding that neurons expressing clock
      proteins already exist in the larval brain and appear to be connected to the
      larval visual system. To define the photoreceptive pathways of the larval clock,
      the authors investigated circadian synchronization during larval stages in
      various visual systems and/or cryptochrome-defective strains. They show that
      adult activity rhythms cannot be entrained by light applied to larvae lacking
      both cryptochrome and the visual system, although such rhythms were entrained by
      larval stage-restricted temperature cycles. Larvae lacking either pathway alone
      were light entrainable, but the phase of the resulting adult rhythm was advanced
      relative to wild-type flies. Unexpectedly, adult behavioral rhythms of the
      glass60j and norpAP24 visual system mutants that were entrained in the same
      conditions were found to be severely impaired, in contrast to those of the wild
      type. Extension of the entrainment until the adult stage restored close to wild
      type behavioral rhythms in the mutants. The results show that both cryptochrome
      and the larval visual system participate to circadian photoreception in larvae
      and that mutations affecting the visual system can impair behavioral rhythmicity.

PMID- 14964701
TI  - Circadian genes in a blind subterranean mammal III: molecular cloning and
      circadian regulation of cryptochrome genes in the blind subterranean mole rat,
      Spalax ehrenbergi superspecies.
AB  - The blind subterranean mole rat superspecies Spalax ehrenbergi is an extreme
      example of mammalian adaptation to life underground. Though this rodent is
      totally visually blind, harboring a drastically degenerated subcutaneous
      rudimentary eye, its daily activity rhythm is entrainable to LD cycles. This
      indicates that it confers light information to the clock, as has been previously
      shown by the authors in behavioral studies as well as by molecular analyses of
      its Clock/MOP3 and its three Per genes. The Cryptochrome (Cry) genes found in
      animals and plants act both as photoreceptors and as essential components of the
      negative feedback mechanism of the biological clock. To further understand the
      circadian system of this unique mammal, the authors cloned and characterized the
      open reading frame of Spalax Cry1 and Cry2. The Spalax CRY1 protein is
      significantly closer to the human homolog than to the mice one, in contrast to
      the evolutionary expectations. They have found two isoforms of Cry2 in Spalax,
      which differ in their 5' end of the open reading frame and defined their
      expression in Spalax populations. They found a large and significant excess of
      heterozygotes of sCry2 (sCry2L/S genotype). Both sCry1 and sCry2 mRNAs were found
      in the SCN, the eye, the harderian gland, as well as in a wide range of
      peripheral tissues. Their expression pattern under different LD conditions has
      also been analyzed. As was already shown for other circadian genes, despite being
      blind and living in darkness, the Cry genes of Spalax behave in a similar, though
      not identical, pattern as in sighted animals. Once again, the results indicate
      that the uniquely hypertrophied harderian gland of Spalax plays a key role in its
      circadian system.

PMID- 14964702
TI  - Temporal precision in the mammalian circadian system: a reliable clock from less
      reliable neurons.
AB  - The mammalian SCN contains a biological clock that drives remarkably precise
      circadian rhythms in vivo and in vitro. This study asks whether the cycle-to
      cycle variability of behavioral rhythms in mice can be attributed to precision of
      individual circadian pacemakers within the SCN or their interactions. The authors
      measured the standard deviation of the cycle-to-cycle period from 7-day
      recordings of running wheel activity, Period1 gene expression in cultured SCN
      explants, and firing rate patterns of dispersed SCN neurons. Period variability
      of the intact tissue and animal was lower than single neurons. The median
      variability of running wheel and Period1 rhythms was less than 40 min per cycle
      compared to 2.1 h in firing rate rhythms of dispersed SCN neurons. The most
      precise SCN neuron, with a period deviation of 1.1 h, was 10 times noisier than
      the most accurate SCN explant (0.1 h) or mouse (0.1 h) but comparable to the
      least stable explant (2.1 h) and mouse (1.1 h). This variability correlated with
      intrinsic period in mice and SCN explants but not with single cells. Precision
      was unrelated to the amplitude of rhythms and did not change significantly with
      age up to 1 year after birth. Analysis of the serial correlation of cycle-to
      cycle period revealed that approximately half of this variability is attributable
      to noise outside the pacemaker. These results indicate that cell-cell
      interactions within the SCN reduce pacemaker noise to determine the precision of
      circadian rhythms in the tissue and in behavior.

PMID- 14964703
TI  - Period and phase control in a multioscillatory circadian system (Iguana iguana).
AB  - The circadian system of the lizard Iguana iguana is composed of several
      independent pacemakers that work in concert: the pineal gland, retinae of the
      lateral eyes, and a fourth oscillator presumed to be located in the hypothalamus.
      These pacemakers govern the circadian expression of multiple behaviors and
      physiological processes, including rhythms in locomotor activity, endogenous body
      temperature, electroretinogram, and melatonin synthesis. The numerous, easily
      measurable rhythmic outputs make the iguana an ideal organism for examining the
      contributions of individual oscillators and their interactions in governing the
      expression of overt circadian rhythms. The authors have examined the effects of
      pinealectomy and enucleation on the endogenous body temperature rhythm (BTR) and
      locomotor activity rhythm (LAR) of juvenile iguanas at constant temperature both
      in LD cycles and in constant darkness (DD). They measured the periods (tau) of
      the circadian rhythms of LAR and BTR, the phase relationships between them in DD
      (psiAT), and the phase relationship between each rhythm and the light cycle
      (psiRL). Pinealectomy lengthened tau of locomotor activity in all animals tested
      and abolished the BTR in two-thirds of the animals. In those animals in which the
      BTR did persist following pinealectomy, tau lengthened to the same extent as that
      of locomotor activity. Pinealectomy also delayed the onset of activity with
      respect to its normal phase relationship with body temperature in DD. Enucleation
      alone had no significant effect on tau of LAR or BTR; however, after enucleation,
      BTR became 180 degrees out of phase from LAR in DD. After both pinealectomy and
      enucleation, 4 of 16 animals became arrhythmic in both activity and body
      temperature. Their data suggest that rhythmicity, period, and phase of overt
      circadian behaviors are regulated through the combined output of multiple
      endogenous circadian oscillators.

PMID- 14964704
TI  - Nocturnal activity in a diurnal rodent (Arvicanthis niloticus): the importance of
      masking.
AB  - It is known that day-active Nile grass rats, Arvicanthis niloticus, increase the
      amount of activity in the night relative to that in the day when provided with
      running wheels. This was confirmed in the present study. Animals without a wheel
      displayed 69.0% of their general activity in the L phase of a 12:12 h light-dark
      cycle; animals provided with wheels had only 48.6% of their wheel revolutions in
      the light. The contribution of direct (masking) responses to light to the
      increased nocturnality of animals with wheels was examined in two experiments. In
      experiment 1, masking was tested by exposing the animals to repeated cycles of 30
      min of entraining light and 30 min of a different, usually dimmer light, during
      the L phase of a 12:12 h light-dark cycle. For animals with wheels, there was
      more running during the 30-min pulses of dim light or darkness than during the 30
      min periods of entraining light. In contrast, for animals without wheels, there
      was more general activity during the 30-min periods of entraining light than
      during the 30-min pulses of dim light or darkness. In experiment 2, the animals
      were first exposed to a 12:12 h light-dark cycle and then put on a 1:10:1:12 h
      LDLD skeleton photoperiod. Animals with wheels increased their running during the
      subjective day of the skeleton photoperiod compared to that in the actual day of
      the 12:12 h light-dark cycle. Animals without wheels showed similar levels of
      general activity during the subjective day of the skeleton photoperiod and the
      actual day of the 12:12 h cycle. These experiments demonstrate that when Nile
      rats have running wheels, their increased nocturnal activity is associated with
      an increased suppression of locomotion in direct response to light. It is
      possible that changes in masking responses to light may be an essential and
      integral component of switching between diurnal and nocturnal activity profiles.

PMID- 14964705
TI  - Eventual entrainment of the human circadian pacemaker by melatonin is independent
      of the circadian phase of treatment initiation: clinical implications.
AB  - About 15% of the legally blind completely lack light perception. Most of these
      individuals have abnormally phased circadian rhythms and many free-run. Light
      treatment is not an option for them. However, melatonin treatment can be highly
      effective. A daily dose of 0.5 mg of melatonin usually results in entrainment. It
      has been suggested that treatment in individuals with circadian periods > 24 h
      should be initiated on the advance zone of the melatonin phase response curve,
      which was based on findings in which melatonin initiated on the delay zone were
      less likely to result in entrainment, even though treatment continued across all
      circadian phases. In the present study, 7 totally blind people started low-dose
      melatonin treatment (0.5 mg; 1 person was given 0.05 mg) on the delay zone. All
      entrained as circadian phase free-ran and the advance zone of the melatonin phase
      response curve coincided with the time of melatonin administration. These results
      are consistent with studies in other mammals. It does not appear that low-dose
      melatonin treatment needs to be initiated on the advance zone to induce eventual
      entrainment in blind people with free-running rhythms > 24 h. Therefore, it is
      not essential that circadian phase be ascertained before starting low-dose
      melatonin treatment of blind people.

PMID- 14964706
TI  - Validation of Horne and Ostberg morningness-eveningness questionnaire in a middle
      aged population of French workers.
AB  - As suggested by the authors, the Horne and Ostberg morning/evening questionnaire
      (MEQ) has never been adapted to evaluate a nonstudent population. The purpose of
      this study was to validate this MEQ in a sample of middle-aged workers by
      modifying only the cutoffs. It was administered in 566 non-shift-workers aged
      51.2 to 3.2 years who presented no sleep disorders. According to the Home and
      Ostberg classification, the sample consisted of 62.1% morning type, 36.6% neither
      type, and 2.2% evening type. Multiple correspondence analysis, which determines
      the principal components, was performed on all MEQ items. Then an ascending
      hierarchical classification was applied to determine 3 clusters from these
      principal components. On the basis of these 3 clusters, new cutoffs were
      determined: evening types were considered as scoring under 53 and morning types
      above 64, thus giving 28.1% morning type, 51.7% neither type, and 20.2% evening
      type. As an external validation, eveningness was associated with later bedtime
      and waking-up time (more pronounced at the weekend), greater need for sleep,
      larger daily sleep debt, greater morning sleepiness, and ease of returning to
      sleep in the early morning. A positive correlation between age and morningness
      was again found. This study confirms that "owls" are not rare in a middle-aged
      sample. We conclude that this adapted MEQ could be useful when investigating age
      related changes in sleep.

PMID- 14964707
TI  - Arousal, changeover responses, and preference in concurrent schedules.
AB  - Pigeons were trained on multiple schedules that provided concurrent reinforcement
      in each of two components. In Experiment 1, one component consisted of a variable
      interval (VI) 40-s schedule presented with a VI 20-s schedule, and the other a VI
      40-s schedule presented with a VI 80-s schedule. After extended training, probe
      tests measured preference between the stimuli associated with the two 40-s
      schedules. Probe tests replicated the results of Belke (1992) that showed
      preference for the 40-s schedule that had been paired with the 80-s schedule. In
      a second condition, the overall reinforcer rate provided by the two components
      was equated by adding a signaled VI schedule to the component with the lower
      reinforcer rate. Probe results were unchanged. In Experiment 2, pigeons were
      trained on alternating concurrent VI 30-s VI 60-s schedules. One schedule
      provided 2-s access to food and the other provided 6-s access. The larger
      reinforcer magnitude produced higher response rates and was preferred on probe
      trials. Rate of changeover responding, however, did not differ as a function of
      reinforcer magnitude. The present results demonstrate that preference on probe
      trials is not a simple reflection of the pattern of changeover behavior
      established during training.

PMID- 14964708
TI  - The resistance to change of observing.
AB  - Observing responses produce contact with discriminative stimuli and have been
      considered analogous to attending. Many studies have examined the effects of
      reinforcement rate on the resistance to change of simple operant behavior, but
      nothing is known about the resistance to change of observing. Two experiments
      examined the effects of primary reinforcement rate on the resistance to change of
      observing behavior of pigeons. In Experiment 1, a multiple schedule of observing
      response procedures was arranged. In a rich component, observing responses
      produced stimuli correlated with a high rate of random-interval (RI)
      reinforcement or extinction. In a lean component, observing responses produced
      stimuli correlated with a lower rate of RI reinforcement or extinction. In both
      components, observing responses produced the multiple-schedule stimuli on a fixed
      interval 0.75-s schedule. In Experiment 2, a similar procedure was used, but
      observing in the rich and lean components produced schedule-correlated stimuli on
      an RI 15-s schedule. Observing in the rich component occurred at a higher rate
      and was more resistant to disruptions produced by presession feeding and response
      independent food deliveries during intercomponent intervals. Despite more
      frequent observing during unsignaled periods of extinction than unsignaled
      periods of RI reinforcement, observing during extinction periods was less
      resistant to change. In addition, replicating the usual result, responding on the
      food key was generally more resistant to change in the presence of stimuli
      associated with higher reinforcement rates. These results suggest that
      quantitative descriptions of resistance to change derived with simple food
      maintained responding may be applicable to observing, and perhaps by extension,
      to attending.

PMID- 14964709
TI  - On the form of the forgetting function: the effects of arithmetic and logarithmic
      distributions of delays.
AB  - Forgetting functions with 18 delay intervals were generated for delayed matching
      to-sample performance in pigeons. Delay interval variation was achieved by
      arranging five different sets of five delays across daily sessions. In different
      conditions, the delays were distributed in arithmetic or logarithmic series.
      There was no convincing evidence for different effects on discriminability of the
      distributions of different delays. The mean data were better fitted by some
      mathematical functions than by others, but the best-fitting functions depended on
      the distribution of delays. In further conditions with a fixed set of five
      delays, discriminability was higher with a logarithmic distribution of delays
      than with an arithmetic distribution. This result is consistent with the
      treatment of the forgetting function in terms of generalization decrement.

PMID- 14964710
TI  - A still great voice: the golden sovereignty of Science and Human Behavior.

PMID- 14964711
TI  - B. F. Skinner's Science and Human Behavior: its antecedents and its consequences.
AB  - Skinner's Science and Human Behavior marked a transition from a treatment of
      behavior that took physics as its reference science to one that emphasized
      behavior as a fundamental part of the subject matter of biology. The book
      includes what may be Skinner's earliest statement about the similarity of operant
      selection to Darwinian natural selection in phylogeny. Other major topics
      discussed in the book included multiple causation, private events, the self, and
      social contingencies. Among the important antecedents were Skinner's own Behavior
      of Organisms and Keller & Schoenfeld's Pincinples of Psychology. Current
      developments in education, behavioral economics, and some behavior therapies can
      be attributed at least in part to Skinner's seminal work. The effective
      behavioral analysis of governmental and religious systems will probably depend on
      elaborations of our understanding of verbal behavior.

PMID- 14964712
TI  - Science and Human Behavior: a tutorial in behavior analysis.
AB  - B. F. Skinner's Science and Human Behavior (1953) became the main source of my
      understanding of behavior during my first semester as a college professor in 1955
      at Kansas University. It has continued to exert a major influence throughout my
      career as the basis for a completely deterministic science of behavior, as a
      handbook to be consulted as a first step in dealing with any issue in behavior
      analysis, and as a tutorial in behavioral interpretive analysis--in the use of a
      small number of behavioral concepts and principles to understand behavior of all
      degrees of complexity. I describe four general interpretive orientations or
      maxims that are of broad significance for behavior analysis, and also two
      underappreciated major theoretical contributions.

PMID- 14964713
TI  - Science and Human Behavior at fifty.
AB  - The golden anniversary of Science and Human Behavior is cause for celebration.
      Toward that end, the present paper is largely an historical consideration of the
      book, its inception and reception, both at the time of its publication and in
      subsequent years. The range and intensity of reactions to S&HB mark its impact
      and show it to be among Skinner's most important works, if not the most
      important. S&HB was written as an introductory psychology text--a vigorous use of
      the book in our teaching could do much to benefit the dissemination of behavior
      analysis.

PMID- 14964714
TI  - Science and Human Behavior translated into Portuguese: Ciencia e Comportamento
      Humano.
AB  - Science and Human Behavior was translated to Portuguese as part of the effort to
      begin a psychology course at the University of Brasilia 40 years ago; one of the
      many results of the first visit of Fred S. Keller to Brazil. The book has been
      used continuously in undergraduate courses in Brazil since 1967.

PMID- 14964715
TI  - Science and Human Behavior, dualism, and conceptual modification.
AB  - Skinner's Science and Human Behavior is in part an attempt to solve psychology's
      problem with mind-body dualism by revising our everyday mentalistic conceptual
      scheme. In the case of descriptive mentalism (the use of mentalistic terms to
      describe behavior), Skinner offers behavioral "translations." In contrast,
      Skinner rejects explanatory mentalism (the use of mental concepts to explain
      behavior) and suggests how to replace it with a behaviorist explanatory
      framework. For experiential mentalism, Skinner presents a theory of verbal
      behavior that integrates the use of mentalistic language in first-person reports
      of phenomenal experience into a scientific framework.

PMID- 14964716
TI  - National Advisory Committee on Immunization (NACI) update on varicella.

PMID- 14964717
TI  - Design characteristics for the tissue engineering of cartilaginous tissues.
AB  - Tissues like the temporomandibular joint (TMJ) disc and the knee meniscus are
      often mistakenly viewed as a tantamount to hyaline cartilage, largely due to the
      absence of a comprehensive understanding of the distinguishing properties of
      cartilaginous tissues. Because of this confusion, fibrocartilaginous tissue
      engineering attempts may not be based on suitable experimental designs.
      Fibrocartilaginous tissues are markedly different than hyaline cartilage;
      however, the dearth of knowledge related to their cellular and biochemical
      composition, as well as their biomechanical characteristics, is stunning. Hyaline
      articular cartilage is exclusively composed of chondrocytes that produce
      primarily type II collagen, whereas the TMJ disc and the knee meniscus have a
      mixed cell population of fibroblasts and cells similar to chondrocytes, which
      predominantly secrete type I collagen. Additionally, fibrocartilaginous tissues
      have a low glycosaminoglycan content, a low compressive modulus, and a high
      tensile modulus when compared to hyaline cartilage. Therefore, it is crucial for
      fibrocartilaginous tissue engineering attempts to be tissue-specific, utilizing
      the knowledge of the distinct and unique properties of these tissues. At the same
      time, advances and insights related to the science and engineering aspect of
      hyaline cartilage regeneration must be carefully considered for the in vitro
      engineering of fibrocartilaginous tissues.

PMID- 14964718
TI  - Mechanical modulation of cartilage structure and function during embryogenesis in
      the chick.
AB  - The mechanical behavior of cartilage is intimately related to its biochemical
      composition, and tissue composition is known to be influenced by its local
      mechanical loading environment. Although this phenomenon has been well-studied in
      adult cartilage, few investigations have examined such structure-function
      relationships in embryonic cartilage. The goal of this work was to elucidate the
      role of mechanical loading on the development of cartilage composition during
      embryogenesis. Using an embryonic chick model, cartilage from the tibiofemoral
      joints of immobilized embryos was compared to that of controls. The normal time
      course of changes in glycosaminoglycan/DNA and hydroxyproline/DNA were
      significantly influenced by loading history, with the most pronounced effects
      observed between days 9 and 14 during the period of most rapid increase in
      motility in control embryos. Stress-relaxation tests conducted on samples from
      day 14 indicate that the effects of embryonic immobilization on cartilage matrix
      composition have direct consequences for the mechanical behavior of the tissue,
      resulting in compromised material properties (e.g. 50% reduction in E(inst)).
      Because embryogenesis provides a unique model for identifying key factors which
      influence the establishment of functional biomechanical tissues in the skeleton,
      these data suggest that treating mechanical loading as an in vitro culture
      variable for tissue engineering approaches to cartilage repair is likely to be a
      sound approach.

PMID- 14964719
TI  - Scaffolds for articular cartilage repair.
AB  - Tissue engineering of articular cartilage seeks to restore the damaged joint
      surface, inducing repair of host tissues by delivering repair cells, genes, or
      polypeptide stimulatory factors to the site of injury. A plethora of devices and
      materials are being examined for their potential to deliver these agents to wound
      sites, and to act as scaffolds for ingrowth of new tissue. This review will
      discuss various promising scaffolds for cartilage tissue engineering
      applications.

PMID- 14964720
TI  - A paradigm for functional tissue engineering of articular cartilage via applied
      physiologic deformational loading.
AB  - Deformational loading represents a primary component of the chondrocyte physical
      environment in vivo. This review summarizes our experience with physiologic
      deformational loading of chondrocyte-seeded agarose hydrogels to promote
      development of cartilage constructs having mechanical properties matching that of
      the parent calf tissue, which has a Young's modulus E(Y) = 277 kPa and unconfined
      dynamic modulus at 1 Hz G* = 7 MPa. Over an 8-week culture period, cartilage-like
      properties have been achieved for 60 x 10(6) cells/ml seeding density agarose
      constructs, with E(Y) = 186 kPa, G* = 1.64 MPa. For these constructs, the GAG
      content reached 1.74% ww and collagen content 2.64% ww compared to 2.4% ww and
      21.5% ww for the parent tissue, respectively. Issues regarding the deformational
      loading protocol, cell-seeding density, nutrient supply, growth factor addition,
      and construct mechanical characterization are discussed. In anticipation of
      cartilage repair studies, we also describe early efforts to engineer cylindrical
      and anatomically shaped bilayered constructs of agarose hydrogel and bone (i.e.,
      osteochondral constructs). The presence of a bony substrate may facilitate
      integration upon implantation. These efforts will provide an underlying framework
      from which a functional tissue-engineering approach, as described by Butler and
      coworkers (2000), may be applied to general cell-scaffold systems adopted for
      cartilage tissue engineering.

PMID- 14964721
TI  - Chondrogenic differentiation of adult dermal fibroblasts.
AB  - Cell sources for generation of articular cartilage ex vivo are limited. To
      explore options other than stem cells, dermal fibroblasts were tested for their
      developmental potential when cultured on the cartilage matrix proteoglycan,
      aggrecan. A previous study suggested such an effort would be successful (M. M.
      French et al., Journal of Cell Biology 145:1103-1115, 1999). The adult dermal
      fibroblast cell line, RAB-9, was used in these assays. While initial attempts to
      differentiate the cells were unsuccessful, after pretreatment with insulin growth
      factor one (IGF-I), the cells were able to differentiate in culture on aggrecan.
      After 24 h in culture on aggrecan, the majority of the cells formed dense
      aggregates reminiscent of condensing mesenchymal cells in development. At 1 week,
      these aggregates stained positively with both Safranin O and antibodies against
      collagen type II. This staining was maintained through the conclusion of the
      experiment at week 4. RT-PCR for collagen II supports the hypothesis that dermal
      fibroblasts can be triggered to differentiate by culture on cartilage matrix
      proteoglycans. A three-fold increase in collagen type II mRNA expression is seen
      when cells are cultured on aggrecan in comparison to controls. These results
      provide an initial step towards a cell source that may prove equally successful
      for the generation of cartilage in the laboratory.

PMID- 14964722
TI  - Repair of extensive articular cartilage defects in horses by autologous
      chondrocyte transplantation.
AB  - Damaged adult articular cartilage has very limited capacity to heal. Autologous
      chondrocyte transplantation (ACT) has been used clinically and studied in
      experimental animals in an attempt to provide biologically based cartilage
      regeneration. This study evaluated cartilage repair following ACT in a large
      animal model over a period of 2 years. Articular cartilage defects (10 mm in
      diameter, full-thickness) were created in the minor load-bearing area on the
      lateral talus of tibiotarsal joints of eight adult horses. In each animal, the
      right joint was repaired using autologous chondrocytes injected beneath the
      periosteum, as in the original ACT procedure (Brittberg, M., A. Lindahl, A.
      Nilsson, C. Ohlsson, O. Isaksson, and L. Peterson N. Engl. J. Med. 331:889-895,
      1994): the left joint remained untreated to serve as a control. Clinical and
      pathological evaluation was within the range of normal for all horses at both
      time points. Compared to untreated defects, ACT resulted in significantly
      improved defect filling with a well-integrated neocartilage and comparable
      expression of cartilage-specific markers. The histological score (Peterson, L.,
      T. Minas, M. Brittberg, A. Nilsson, E. Sjogren-Jansson, and A. Lindahl Clin.
      Orthop. 374:212-234, 2000) (10.4 +/- 0.9 for ACT and 5.6 +/- 3.9 for controls,
      all animals, p = 0.016) indicated that ACT contributed to the reparative process.
      For the first time, the efficacy of ACT was demonstrated in a large animal model
      supporting the potential of ACT for cartilage regeneration in patients.

PMID- 14964723
TI  - Intervertebral disc mechanics are restored following cyclic loading and unloaded
      recovery.
AB  - The objectives of this study were (1) to quantify changes in the mechanical
      behavior of the intervertebral disc in response to cyclic compressive loading and
      (2) to determine whether mechanical behavior would be restored following a period
      of unloading. The elastic and viscoelastic compressive mechanical behaviors of
      adult sheep motion segments were assessed. Ten thousand cycles of compressive
      loading resulted in increased elastic stiffness and decreased stress-relaxation.
      After 18 h of unloading in a PBS bath stiffness and relaxation were fully
      restored. Cyclic loading did not cause structural damage as determined by
      radiographs and magnetic resonance images. After cyclic loading, average
      stiffness increased from 603 to 800 N/mm (p = 0.015) and returned to initial
      levels after the recovery period. Cyclic loading caused a decrease in total
      relaxation (from 92 to 38 N, p < 0.001) that also returned to initial levels
      after recovery. The reversible, repeatable effects of cyclic loading and recovery
      demonstrated in this in vitro study may be attributed to fluid flow.
      Intervertebral disc fluid transport during the diurnal recovery cycle may be key
      to understanding intervertebral disc degeneration, as fluid exudation and
      recovery may be integral to maintaining adequate disc nutrition.

PMID- 14964724
TI  - Evolution of vertebroplasty: a biomechanical perspective.
AB  - This paper is a collection of computational, finite element studies on
      vertebroplasty performed in our laboratory, which attempts to provide new
      biomechanical evidence and a fresh perspective into how the procedure can be
      implemented more effectively toward the goal of preventing osteoporosis-related
      fractures. The percutaneous application of a bone cement to vertebral defects
      associated with osteoporotic vertebral compression fracture has proven clinical
      successful in alleviating back pain. When the biomechanical efficacy of the
      procedure was examined, however, vertebroplasty was found to be limited in its
      ability to provide sufficient augmentation to prevent further fractures without
      risking complications arising from cement extravasations. The procedure may
      instead be more efficient biomechanically as a prophylactic treatment, to
      mechanically reinforce osteoporotic vertebrae at risk for fracture. Patient
      selection for such intervention may be reliably achieved with the more accurate
      fracture risk assessments based on vertebral strength, predicted using
      geometrically detailed, specimen-specific finite element models, rather than on
      bone density alone. Optimal cement volume, placement, and material properties
      were also recommended. The future of vertebroplasty involving biodegradable
      augmentation material laced with osteogenic agents that upon release will
      stimulate new bone growth and increase bone mass was proposed.

PMID- 14964725
TI  - A nonlinear hyperelastic mixture theory model for anisotropy, transport, and
      swelling of annulus fibrosus.
AB  - A precise knowledge of the local mechanical and chemical environment around the
      nerve endings and disc cells in the annulus fibrosus will shed insight on
      understanding the mechanism of low-back pain and disc degeneration. It would also
      present an effective tool for the studies of the intervertebral disc structure
      function relationship and provide guidance to disc tissue engineering.
      Experimental difficulties preclude the direct and simultaneous measurement of
      many of the important physical quantities, such as annulus pressurization,
      nutrient and electrolyte transport, and mechanical and swelling deformation.
      Considering that many of these quantities are coupled and that the annulus is
      highly anisotropic, interpretation of the results would be extremely challenging
      without an appropriate theoretical framework. In this study, we develop a
      nonlinear hyperelastic fiber-reinforced continuum mixture theory model for the
      annulus fibrosus. Special attention is given to the anisotropic nature of the
      annulus. On the basis of the lamella structure of annulus, and derived from a
      Helmholtz energy function, a locally transversely isotropic stress-strain
      relation is adopted for explicit representation of the collagen fiber
      orientations in general finite deformation situation. The exponential form of the
      Helmholtz energy function naturally reduces to the infinitesimal deformation
      form, and the equivalence between the current model coefficients and engineering
      elastic constants is established under the infinitesimal deformation. This model
      is able to describe the anisotropic finite and infinitesimal deformation, tension
      compression nonlinearity, osmotic swelling, pressurization, electrical potential
      and current, and water and ion transports as well as the electroneutral nutrient
      (or growth factor) transport within the annulus.

PMID- 14964726
TI  - The role of F-actin in hypo-osmotically induced cell volume change and calcium
      signaling in anulus fibrosus cells.
AB  - Loading of the spine induces dynamic changes in the osmotic environment of the
      intervertebral disc (IVD) due to the exudation and recovery of tissue water.
      Cells from the anulus fibrosus (AF) respond to osmotic stress with altered
      biosynthesis through a pathway that may involve calcium (Ca2+) as a second
      messenger. We examined the hypothesis that AF cells respond to hypo-osmotic
      stress by swelling and initiating regulatory volume decrease (RVD). Further, the
      role of F-actin disruption and transient increases in intracellular calcium
      concentration ([Ca2+]i) in volume adaptation were studied. In response to hypo
      osmotic stress, AF cells swelled, disrupted F-actin, and exhibited [Ca2+]i
      transients in proportion to the magnitude of the stress. The transient disruption
      of F-actin was dependent on the presence of extracellular Ca2+. After swelling,
      AF cells underwent RVD at all magnitudes of hypo-osmotic stress. The extent of
      RVD was diminished significantly by F-actin breakdown using cytochalasin D or by
      inhibition of swelling-induced F-actin disruption by removing extracellular Ca2+.
      Swelling-induced disruption of F-actin facilitated RVD, as evidenced by a more
      rapid volume recovery with increased F-actin breakdown. In conclusion, our
      findings suggest that the F-actin network plays an important role in the response
      of AF cells to osmotic stress.

PMID- 14964727
TI  - Bone tissue engineering using human mesenchymal stem cells: effects of scaffold
      material and medium flow.
AB  - We report studies of bone tissue engineering using human mesenchymal stem cells
      (MSCs), a protein substrate (film or scaffold; fast degrading unmodified
      collagen, or slowly degrading cross-linked collagen and silk), and a bioreactor
      (static culture, spinner flask, or perfused cartridge). MSCs were isolated from
      human bone marrow, characterized for the expression of cell surface markers and
      the ability to undergo chondrogenesis and osteogenesis in vitro, and cultured for
      5 weeks. MSCs were positive for CD105/endoglin, and had a potential for
      chondrogenic and osteogenic differentiation. In static culture, calcium
      deposition was similar for MSC grown on collagen scaffolds and films. Under
      medium flow, MSC on collagen scaffolds deposited more calcium and had a higher
      alcaline phosphatase (AP) activity than MSC on collagen films. The amounts of DNA
      were markedly higher in constructs based on slowly degrading (modified collagen
      and silk) scaffolds than on fast degrading (unmodified collagen) scaffolds. In
      spinner flasks, medium flow around constructs resulted in the formation of bone
      rods within the peripheral region, that were interconnected and perpendicular to
      the construct surface, whereas in perfused constructs, individual bone rods
      oriented in the direction of fluid flow formed throughout the construct volume.
      These results suggest that osteogenesis in cultured MSC can be modulated by
      scaffold properties and flow environment.

PMID- 14964728
TI  - The toughness of cortical bone and its relationship with age.
AB  - Toughness is a quantitative measure of bone quality in terms of its
      susceptibility to fracture. Thus, to elucidate the underlying mechanisms of age
      related bone fractures, it is necessary to understand age-related changes in the
      toughness of bone. The objective of this review is to provide current
      understanding on the structure-function relationships of cortical bone and its
      correlation with the toughness of the tissue from the perspective of basic
      engineering principles. The review is written for the readers in the
      musculoskeletal research field, who may not have a strong engineering background.
      For better understanding of toughening mechanisms, this review intends to focus
      on correlations of the toughness of cortical bone with its constituents and
      microstructural characteristics. In addition, a special emphasis is placed on age
      related changes in the toughness of bone.

PMID- 14964729
TI  - Genetic modification of stem cells to enhance bone repair.
AB  - Orthopaedic surgeons are often faced with difficult bone loss problems.
      Conventional bone grafting is usually accomplished with autogenous iliac crest
      bone graft that provides osteogenic cells, osteoinductive growth factors, and an
      osteoconductive matrix. Cadaveric bone allograft and bone graft substitutes are
      inferior to autogenous bone graft because they fail to supply osteogenic cells or
      a significant amount of osteoinductive growth factors. Recombinant growth factors
      such as bone morphogenetic protein-2 and osteogenic protein-1 are currently in
      clinical use but these proteins require supraphysiologic dosing and considerable
      expense while failing to provide a sustained osteoinductive signal at the
      implantation site. Mesenchymal stem cells capable of differentiating into
      mesodermal tissues have been isolated and expanded in culture from several
      different sources including bone marrow, adipose tissue, and muscle. In the
      presence of appropriate growth factors these cells can differentiate into
      osteoblast lineage cells that will form bone in vitro and in vivo. Recent
      attention has focused on genetic modification of mesenchymal stem cells to both
      produce and respond to osteogenic growth factors with the goal of developing a
      tissue engineering strategy for bone repair. This review examines the current
      potential and limitations of these cellular systems for bone repair.

PMID- 14964730
TI  - Engineering structurally organized cartilage and bone tissues.
AB  - The field of tissue engineering promises to deliver biological substitutes to
      repair or replace tissues in the body that have been injured or diseased. The
      clinical demand for musculoskeletal tissues is particularly high, especially for
      cartilage and bone defects. Although they are generally considered biologically
      simple structures, musculoskeletal tissues consist of highly organized three
      dimensional networks of cells and matrix, giving rise to tissue structures with
      remarkable mechanical properties. Although the field of cartilage and bone tissue
      engineering has progressed significantly in recent years, the development of
      structurally ordered tissues has not been accomplished. More strategies are
      needed to ensure that the appropriate cell and matrix organization is being
      achieved in the engineered tissues. This review emphasizes how different cell
      types and scaffold designs can be used to modulate tissue properties and engineer
      more complex tissue structures, with emphasis on cartilage and bone tissues.

PMID- 14964731
TI  - Bone marrow stromal cells (BMSCs) in bone engineering: limitations and recent
      advances.
AB  - Bone marrow stromal cells (BMSCs) have been isolated for the first time by
      Friedenstein et al. and since then have been considered the progenitor cells for
      the skeletal tissues. Indeed BMSCs are clonogenic, fibroblastic in shape, and can
      differentiate along multiple lineages such as osteoblasts, chondrocytes,
      adipocytes, and hematopoiesis-supportive stroma. When implanted in vivo on a
      three-dimensional bioceramic scaffold into immunocompromised mice, BMSCs form
      bone and hematopoiesis-supportive stroma. The ease of harvest from a donor bone
      marrow together with the ability to form bone in vivo make BMSCs ideal for
      clinical applications. Thus, ex vivo expanded BMSCs have been employed, first in
      large animal models, then in human clinical trials, to repair large bone
      segmental defects. Further investigation of the expanded BMSC population led to
      the observation that in vitro expansion appears a limiting passage: cells tend to
      senesce and lose their multidifferentiation potential with time in culture. To
      overcome these limitations, two approaches have been proposed: (1) identification
      of the appropriate culture conditions to prevent senescence by possibly selecting
      a subpopulation with stem cell characteristics, and (2) engineering of the cells
      by transfection with the telomerase gene to prevent cells from telomere
      shortening and consequent aging.

PMID- 14964732
TI  - The principle of margin convergence in rotator cuff repair as a means of strain
      reduction at the tear margin.
AB  - The principle of margin convergence applied to rotator cuff repair is achieved by
      side-to-side suture of the cuff tear in order to converge the free margin of the
      cuff toward its bone bed. This technique dramatically reduces strain along the
      "converged" margin, thereby protecting the tendon-bone repair interface during
      the critical phases of healing.

PMID- 14964733
TI  - Bioabsorbable implants: review of clinical experience in orthopedic surgery.
AB  - Bioabsorbable implants are widely used in orthopedic surgery today and the
      worldwide market is expanding rapidly. Despite the popularity of these implants,
      reports of complications continue to appear in the literature. Although the
      complications rarely have an adverse affect on long-term outcomes, the reports
      are too numerous to be mere isolated incidents related to one specific implant.
      Complications have been reported with most of the commercially available implant
      materials with varying incidence rates and severities of reactions to the
      implants. The purpose of this review is to summarize the adverse events that have
      been reported in clinical trials of bioabsorbable implants in orthopedic surgery.

PMID- 14964734
TI  - Protective effect of nerve growth factor on neurons after traumatic brain injury.
AB  - The protective effect of nerve growth factor (NGF) on neurons after traumatic
      brain injury (TBI) was investigated. A brain trauma model of fluid-percussion in
      rats was established, and 7s NGF was infused continuously in its cerebral
      ventricle. The activity of superoxide dismutase (SOD), glutathione peroxidase
      (GSH-Px) and catalase (CAT), and [Ca2+]i overloading in brain tissues was
      observed after giving exogenous NGF postinjury. We found that the activity of
      SOD, GSH-Px, and CAT was markedly higher in NGF-treated group than in the simple
      trauma group (P < 0.01). Although the level of [Ca2+]i in the NGF-treated group
      increased, the value was significantly lower than that in the simple trauma and
      control groups (P < 0.01). These findings suggest that exogenous NGF can (a)
      increase the activity of the major antioxidant enzymes in brain tissues and
      attenuate the injuries to neurons induced by oxygen-free radicals, (b) reduce the
      severe overload of [Ca2+]i and stabilize its homeostasis, and (c) provide clear
      protective effects on neurons after traumatic brain injury.

PMID- 14964735
TI  - Temporal distribution of death among oncology patients: environmental links.
AB  - BACKGROUND: The natural history of terminal oncologic disease is death from
      cardiopulmonary arrest. The goal of this study was to determine whether the
      temporal distribution of death among oncology patients is related to levels of
      environmental physical activity-solar, geomagnetic, and cosmic rays and high
      energy space proton flux, as previously shown for other situations like
      accidents, suicide, and the occurrence of acute myocardial infarction.
      EXPERIMENTAL: Deaths of oncology patients, n = 102604, in 168 consecutive months
      were compared with-monthly indices of solar, geomagnetic, cosmic rays activity
      (sunspot number, solar flux, Ap, Cp, Am), and indices of magnetic and cosmic rays
      activity according to neutron monitor data). In addition, oncology patients
      monthly death numbers were compared with numbers of deaths from ischemic heart
      disease (IHD), stroke, sudden cardiac death (SCD), accidents, road accidents, non
      cardiovascular death (total deaths - [IHD + stroke]). The National Data of the
      Republic of Lithuania was used, excluding SCD and myocardial infarction in Kaunas
      -the second largest city in Lithuania Monica study register was used for SCD at
      age 25-64, and all data of AMI. Pearson correlation coefficients and their
      probabilities were obtained between the numbers of oncology patient monthly
      deaths and (1) cosmo-physical indices and (2) the number of deaths from other
      causes and the occurrence of AMI. RESULTS: The number of oncology patient deaths
      was inversely correlated with solar and geomagnetic activity indices and
      positively correlated with cosmic rays activity. The number of oncology patient
      deaths was correlated with monthly number of deaths from non-cardiovascular
      courses, stroke, suicide, at trend level with SCD, but not with deaths from IHD,
      accidents, road accidents. Oncology patient deaths showed a significant
      correlation with the number of AMI. CONCLUSION: The monthly death number of
      oncology patients is significantly related with environmental physical activity
      and shows similarity with deaths distribution by time of some other groups of
      death--stroke, SCD, suicide, and occurrence of AMI. The inverse correlation with
      solar and geomagnetic activity and positive links with cosmic rays activity level
      are remarkable.

PMID- 14964736
TI  - Cardiovascular effects of intravenous pentazocine and cyclazocine in conscious,
      curarized-conscious, and anesthetized dogs.
AB  - The cardiovascular effects of intravenous pentazocine and cyclazocine in dogs
      were studied under conscious, curarized-conscious (paralyzed by gallamine), and
      anesthetized states. In the conscious state, blood pressure and heart rate were
      dose-dependently increased by pentazocine (1, 2, 3 mg/kg) and to a lesser extent
      by cyclazocine (0.3 mg/kg). In all subsequent experiments on dogs, the results
      were obtained using 3 mg/kg pentazocine and 0.3 mg/kg cyclazocine. Pentazocine
      accelerated breathing, peaking at about 10 min, whereas cyclazocine reduced
      breathing to a minimum in 1 min, followed by a gradual recovery thereafter. In
      the curarized-conscious state, the blood pressure response to pentazocine was
      biphasic, namely an initial decrease followed by an increase; chronotrophic
      activity was stimulated. Pretreatment with either ganglionic or alpha andrenergic
      blocking agents not only significantly antagonized the pressory responses to the
      drug but also potentiated the initial decreases in blood pressure and unmasked a
      bradycardic component, but these parameters were not altered by 0.3 mg/kg
      naxalone. In open-chest anesthetized dogs, blood pressure, heart rate,
      contractility, and mean peripheral vascular resistance were simultaneously
      decreased by both pentazocine and cyclazocine, initially accompanied by increases
      in aortic blood flow. During the later stages of drug action, only the blood
      pressure and contractility were increased above control levels (biphasic effect).
      A comparison of blood pressure and heart rate responses to pentazocine in dogs
      kept under differing experimental conditions revealed that conscious dogs were
      more sensitive than curarized conscious and anesthetized animals to pentazocine
      action. In isolated guinea pig atria, the effect of adrenaline (0.1, 0.3, or 1
      mg/mL) on the spontaneous breathing rate was significantly augmented by 10 mg/mL
      pentazocine (p < 0.02 for 0.3 g/mL; p < 0.01 for 0.1 g/mL adrenaline). In dogs,
      however, adrenaline (1 mg/kg)-induced increases in heart contractility, aortic
      blood flow, and blood pressure remained almost unaltered in the presence of
      pentazocine. We concluded that the abovementioned cardiovascular responses to
      pentazocine and cyclazocine are a consequence of the sum of the two following
      opposing effects: (i) an indirect reflex activation of sympathetic neuromediation
      in the periphery, and (ii) a direct membrane effect on the heart leading to
      bradycardia and a depression in myocardial contractility.

PMID- 14964737
TI  - Intramuscular administration of lidocaine or bupivacaine alters the effect of
      midazolam from sedation to hypnosis in a dose-dependent manner.
AB  - We examined the sedative/hypnotic interaction between the administration of
      intravenous (i.v.) midazolam and intramuscular (i.m.) lidocaine or bupivacaine.
      Women undergoing gynecological surgery (n = 150) were randomly assigned to 15
      dose groups of 10 patients each. Fifty patients received one of five
      predetermined doses of midazolam for the calculation of its median effective dose
      (ED50). The remaining patients (n = 100) received i.v. midazolam 0.1 mg/kg
      following an i.m. injection of either bupivacaine, lidocaine, or saline
      (control). Three minutes after the i.v. dose, the loss of response to verbal
      command was evaluated. The ED50 of midazolam was 0.226 mg/kg (95% confidence
      interval [CI] 18-027; p = 0.03). Both bupivacaine and lidocaine enhanced the
      effect of midazolam in a dose-dependent fashion. The hypnotic ED50 for
      bupivacaine and lidocaine was 0.7 mg/kg (95% CI 0.5-1.0) and 3.32 mg/kg (95% CI
      2.2-11.7), respectively. The slopes of the dose-response curves were
      significantly different (p < 0.01). Local anesthetics that are well within the
      range of clinical use for regional blocks or local infiltration can bring the
      effect of midazolam from the sedative into the hypnotic range.

PMID- 14964738
TI  - Analysis of visual evoked potentials and background electroencephalographic
      activity in young and elderly subjects.
AB  - OBJECTIVE: New techniques developed in this laboratory to overcome the loss of
      information involved in conventional evoked potential averaging are applied here
      to visual evoked potential (VEP) in young and elderly normal subjects. METHODS:
      The techniques are based on statistical descriptions of the times and amplitudes
      of the electroencephalographic deflections recorded before (background) and after
      (evoked) a series of pattern reversal visual stimuli. RESULTS: The elderly had a
      higher rate of background deflections at all electrode sites, but lower
      amplitudes at the occipital electrodes. The elderly had a lower rate of
      deflections during the period of evoked activity compared with the background
      period. The young had a higher degree of response deflection time locking and
      amplitude. The mean amplitude of the deflections recorded during the period of
      evoked activity was significantly greater in amplitude than the background
      deflections and greater than the amplitudes of the conventionally averaged VEP
      derived from the same data. Thus the lower amplitude VEPs seen in the elderly are
      due to their poor time locking and reduced amplification. Only 79% of the
      stimulus trials contributed deflections to the P1 response component in both
      young and elderly subjects and 63% to the N1. In young subjects, several of the
      new response parameters showed the presence of evoked response components that
      were not apparent in the conventionally averaged VEP derived from the same data.
      CONCLUSIONS: The novel methods presented here provide a great deal of additional
      information that is unavailable when analyzing data using only conventional
      evoked potential averaging.

PMID- 14964739
TI  - Eurycoma longifolia Jack enhances sexual motivation in middle-aged male mice.
AB  - Eurycoma longifolia Jack was investigated for sexual motivation activity in
      adult, middle-aged male mice and in retired breeders, using the modified open
      field and the modified runway choice methods. Each mouse received 500 mg/kg of
      one of 4 fractions of E. longifolia Jack, viz. chloroform, methanol, butanol, and
      water, whereas the mice in the control and yohimbine groups received 3 ml/kg of
      normal saline and 30 mg/kg of yohimbine daily respectively for 10 d. The results
      show a transient increase in the percentage of male mice responding to the right
      choice after chronic consumption of the fractions with 50 percent of the adult
      middle-aged male mice treated with E. longifolia Jack and yohimbine scoring the
      right choice after 8 and 5 days post-treatment respectively. In conclusion, this
      study has shown that E. longifolia Jack continues to enhance sexual motivation in
      adult, middle-aged male mice and in retired breeders.

PMID- 14964740
TI  - And the beat goes on: formulary restriction, generic substitution, prior
      authorization, drug utilization, and now therapeutic interchange.

PMID- 14964741
TI  - Diphenhydramine gargling may slow the healing of oral lesions of pemphigus
      vulgaris.

PMID- 14964742
TI  - Redefining clinical response in psoriasis: targeting the pathological basis of
      disease.
AB  - Psoriasis is a chronic inflammatory disease of the skin that can have a major
      effect on patient quality of life. Conventional psoriasis treatments, often
      identified empirically, fail to meet the clinical needs for a safe and remittive
      therapy. These unmet needs, together with the rapid advances in understanding the
      molecular basis of psoriasis, have led to the development of targeted biologic
      therapies. Using recombinant DNA technology, a new generation of therapeutic
      agents is being designed to interfere at specific pathogenic steps that involve T
      cells or T-cell-mediated immune responses. These targeted therapies promise
      improved tolerability and safety in the treatment of psoriasis. Furthermore, they
      will redefine clinical response in psoriasis by providing long-lasting remissions
      of disease and extended treatment-free periods.

PMID- 14964743
TI  - Topical treatment of actinic keratosis with fluorouracil: is irritation
      associated with efficacy?
AB  - Actinic keratoses (AKs) are common dysplastic epidermal lesions that share
      clinical, histologic, and molecular features with squamous cell carcinoma.
      Therapeutic options include destructive modalities (i.e., cryosurgery, curettage)
      or topical fluorouracil treatment. The efficacy of topical fluorouracil for the
      treatment of widespread AK lesions has been demonstrated in multiple studies, but
      treatment is often associated with significant skin irritation. Various
      approaches to decrease irritation while maintaining efficacy have been attempted,
      including altered treatment regimens, combination therapies, and variations in
      vehicle formulations. Recently, a novel topical fluorouracil cream that contains
      0.5% 5-fluorouracil in a microsphere vehicle has been approved for the treatment
      of AK. Data demonstrate that this low-dose formulation is effective in reducing
      AK lesions while maintaining a tolerable irritation profile.

PMID- 14964744
TI  - Impact of efalizumab on psoriasis-specific patient-reported outcomes. Results
      from three randomized, placebo-controlled clinical trials of moderate to severe
      plaque psoriasis.
AB  - The objective of this study was to document the disease burden associated with
      moderate to severe plaque psoriasis, and assess the impact of efalizumab
      psoriasis treatment in improving patient-reported outcomes. This included
      analysis of patient-reported dermatology-related quality of life (DRQL) and
      psoriasis symptom scores among patients with moderate to severe psoriasis
      participating in three phase III, randomized, double-blinded, parallel-group,
      placebo-controlled, multi-center clinical trials conducted to evaluate the
      efficacy and safety of efalizumab. A total of 1,242 patients with moderate to
      severe psoriasis treated either with efalizumab 1.0 mg/kg/wk or placebo were
      followed for 12 weeks. DRQL and psoriasis symptom severity were assessed at
      baseline (pre-treatment) and at the end of the first treatment phase (12 weeks).
      DRQL was measured using the Dermatology Life Quality Index (DLQI). Symptoms were
      measured using the Psoriasis Symptom Assessment (PSA) and an Itch scale. Disease
      burden was assessed at baseline by examining responses to individual questions of
      the DLQI, PSA, and Itch patient-reported outcome measures. The impact of
      treatment on disease burden was assessed over a 12-week double-blind study period
      by comparing changes in DLQI, PSA, and Itch scale scores between the active
      treatment and placebo groups. Patient-reported outcomes were also assessed during
      a 12-week extended treatment phase. Prior to treatment, the responses to DLQI and
      PSA items revealed significant disease burden. Greater than 90% of patients
      reported being embarrassed or self conscious because of their skin, 53% reported
      that their skin prevented them from working or studying. and 98% reported that
      scaling and itching was bothersome. Compared to placebo-treated patients,
      efalizumab-treated patients showed significant improvement in patient-reported
      outcomes, reducing the limitations and burden associated with moderate to severe
      psoriasis within each of the three studies, as measured by DLQI (p<0.001), PSA
      Severity (p<0.001), PSA-Frequency (p<0.001), and Itch (p<0.001) scores. Across
      all measures, the proportion of patients that improved on both statistical and
      clinical criteria for meaningful improvement was at least twofold greater among
      efalizumab-treated patients than in placebo-treated patients. The benefit of
      efalizumab was maintained over the course of an additional 12 weeks during an
      extended treatment phase. In conclusion, patients with moderate to severe plaque
      psoriasis reported significant DRQL burden and symptom severity at baseline, but
      efalizumab significantly improved patient-reported DRQL and reduced the frequency
      and severity of psoriasis symptoms during 12-week double-blind and 12-week
      extended treatment periods.

PMID- 14964745
TI  - Photorejuvenation with intense pulsed light: results of a multi-center study.
AB  - This multi-center study evaluating the role of Intense Pulsed Light (IPL) in the
      non-ablative rejuvenation of Type I and Type II photoaged skin study was
      conducted in order to evaluate the clinical efficacy and safety of using IPL in
      treating clinical indications associated with photoaged skin. Ninety-three
      patients of Fitzpatrick skin phenotypes I-III, Fitzpatrick Wrinkle Classes I-II,
      and Elastosis Scores 1-6 were enrolled in the study. Up to five treatments were
      performed at 4-week intervals with follow-up visits at 4 and 6 months after the
      last treatment. Patients received full-face treatments using the recommended
      parameters of the Quantum SR/HR (Lumenis Ltd.) with the 560 or 640 nm cutoff
      filter. Parameters of elastometry, physicians' evaluation of the Elastosis Score
      ('W/ES'), and global improvement as well as patient satisfaction were analyzed.
      Results showed that the average Fitzpatrick W/ES improved significantly (p<0.001)
      by 1.39 and 1.32 units at the 4 and 6 months follow-ups, respectively; an
      improved W/ES evaluation was recorded for 82% and 75% of the patients at each of
      these time points. In conclusion, IPL treatment is an effective non-invasive, non
      ablative method for rejuvenating photoaged skin with minimal adverse events, no
      downtime, excellent long-term results, and a very high measure of patient
      satisfaction.

PMID- 14964746
TI  - Onychomycosis: classification and diagnosis.
AB  - Onychomycosis is a common infection of the nail predominantly caused by
      anthropophilic dermatophytes, and to a lesser extent by yeasts (Candida species)
      and non-dermatophyte molds. The treatment of onychomycosis is dependent on
      several variables, including the type of onychomycosis and the causative
      organism. Various techniques have been used to accurately diagnose onychomycosis,
      with microscopy and culture being used most frequently. Histological examination
      of the distal nail plate can aid in confirming the presence of invasive nail
      disease, but histological examination should not be limited to the nail plate as
      it may also be helpful in diagnosing subungual onychomycosis. Nucleic acid-based
      identification techniques may also be valuable when diagnosing onychomycosis;
      however, multiple steps may be necessary to determine the causative species.
      Confocal microscopy may also be a fast and reliable method of diagnosing
      onychomycosis, though it has very limited ability to distinguish between
      dermatophyte and mold infections. Prior to treatment an accurate diagnosis can
      provide guidance about the choice of antifungal agent, especially since the
      causative organism may vary in its response to the antifungal therapies
      available.

PMID- 14964747
TI  - Picaridin: a new insect repellent.
AB  - Picaridin is a new insect repellent that is comparable in effect and less
      irritating than diethyl toluamide (deet). Its activity and effects are reviewed
      in this article.

PMID- 14964748
TI  - Dermatologic look- or sound-alike medications.
AB  - Medication errors contribute substantially to patient injury and death, with 25%
      of these errors attributed to drug names that look or sound alike. This article
      was written to heighten the awareness of dermatologists and related health care
      professionals of confusing dermatologic drug names and includes a table of 166
      look- and sound-alike drug names. Measures to decrease medication errors due to
      confusing drug nomenclature in dermatology are suggested in order to maximize
      patient safety.

PMID- 14964749
TI  - The nuances of dealing with cosmetic patients.

PMID- 14964750
TI  - Imiquimod as a possible treatment for keratoacanthoma.
AB  - Imiquimod is an immune-response modifier that has the potential to be useful in
      many dermatological indications (Table 1). To date, the approved use is for
      condyloma acuminata; approval for use in treating basal cell carcinoma (BCC) has
      been filed with the FDA and is expected to be approved in the coming months. In
      the interim, the expansion of the horizons for this immunomodulator depends on
      the application of the science and immunology behind the drug to the appropriate
      disease states. Recent investigations have presented explanations on the possible
      mechanisms behind the anti-tumor activity of imiquimod, more specifically for its
      use in treating superficial BCC. There are studies currently underway as well as
      anecdotal data published for its possible use in treating squamous cell carcinoma
      (SCC), although this is not as widely accepted for off-label use as BCC among
      many dermatologists. However, many patients who may not be surgical candidates
      that present with tumors other than BCC have been successfully treated with
      imiquimod. This is a case of an elderly patient who could not undergo surgery
      that presented with a large keratoacanthoma and was clear of her tumor after five
      months using imiquimod 5% cream on a daily basis.

PMID- 14964751
TI  - Localized heat induced urticaria: report of a case.
AB  - Localized heat induced urticaria is a rare clinical entity. Other physical
      urticarial subtypes include cholinergic, solar, cold, aquagenic, vibratory, and
      dermatographic. It is characterized by a well-demarcated urticarial lesion
      provoked by heat in direct contact with the skin. We describe a case of localized
      heat-induced urticaria in a 49-year-old woman after a heat-challenge test to her
      forearm.

PMID- 14964752
TI  - Generalized pustular psoriasis following withdrawal of efalizumab.
AB  - Efalizumab is one of the new biologic therapies targeting T-lymphocyte activity
      for the treatment of chronic plaque psoriasis. Common adverse effects include
      headaches, nonspecific infection, nausea, chills, and fever. Rebound of psoriasis
      following discontinuation of the drug has been reported. Relapse events can
      manifest as recurrent plaque psoriasis, guttate psoriasis, psoriatic
      erythroderma, and pustular psoriasis. We report a second case of withdrawal flare
      resulting in generalized pustular psoriasis.

PMID- 14964753
TI  - Cutaneous vasculitis secondary to ramipril.
AB  - A 61-year-old patient who had been treated with lisinopril in the past without
      any problems was commenced on ramipril for left ventricular dysfunction. He
      developed a painful symmetrical purpuric eruption over both feet after three
      days. A full vasculitis screen was negative. Ramipril was stopped and he required
      a course of steroids after which the rash improved slowly. The ACE inhibitors can
      cause various skin side effects; however, it rarely causes cutaneous vasculitis.
      Ramipril-induced cutaneous vasculitis is particularly rare and our case was
      atypical because the patient had tolerated lisinopril before. Previous successful
      treatment with one ACE inhibitor does not rule out the vasculitis caused by the
      drug from the same group. Here we report ramipril-induced cutaneous vasculitis in
      a patient who required steroid therapy to control it.

PMID- 14964754
TI  - Venous thrombosis occurring after initiation of thalidomide for the treatment of
      cicatricial pemphigoid.
AB  - Thalidomide is increasingly being used for the treatment of a variety of
      dermatologic conditions. Some of the risks associated with thalidomide use,
      however, are still being uncovered. Increased incidence of venous thrombosis
      following thalidomide use has recently been reported in the treatment of diseases
      with disease-related thrombotic risks, such as malignancy and lupus with
      antiphospholipid antibody syndrome. We report a case of venous thrombosis
      resulting from thalidomide use in a patient with cicatricial pemphigoid,
      illustrating the potential concern for increased thrombosis following thalidomide
      use in the dermatology setting.

PMID- 14964755
TI  - Primary cutaneous B-cell lymphoma in a 74-year-old Caucasian male.
AB  - Primary cutaneous B-cell lymphoma is an uncommon neoplasm with classification
      schemes that may be confusing, but with clinical presentations that are
      relatively consistent. Clinical exam and history can raise the index of suspicion
      for this condition, although the diagnosis is confirmed only by pathological
      evaluation. We report such a scenario in the case of a 74-year old male with a
      slowly expanding oval plaque on his right upper arm.

PMID- 14964756
TI  - Genetic testing for inherited predisposition to melanoma: has the time come?

PMID- 14964757
TI  - Photodynamic therapy in dermatology: history and horizons.
AB  - Photodynamic therapy (PDT) uses a photosensitizer, light, and molecular oxygen to
      selectively kill cells. When localized in the target tissue, the photosensitizer
      is activated by light to produce oxygen intermediates that destroy target tissue
      cells. The easy access of skin to light-based therapy has led dermatologists to
      apply PDT to cutaneous disorders. In dermatology, PDT has been most successful in
      treating actinic keratoses, basal cell carcinoma, and Bowen's disease. The
      introduction of aminolevulinic acid, which does not make patients susceptible to
      phototoxicity for extended periods, has reduced morbidity associated with PDT.
      This has led to new interest in PDT not only for nonmelanoma skin cancer and
      premalignant lesions but also in the treatment of acne and as an adjuvant to
      photorejuvenation procedures. This review examines the historical roots of PDT
      and the research evaluating different light and laser sources as well as reports
      on new horizons for PDT in dermatology.

PMID- 14964758
TI  - Large surface photodynamic therapy with aminolevulinic acid: treatment of actinic
      keratoses and beyond.
AB  - Photodynamic therapy (PDT) with topical aminolevulinic acid (ALA) is currently
      approved in the US and Canada for the spot treatment of non-hypertrophic actinic
      keratoses of the face and scalp. Dermatologists are currently using ALA-PDT on
      larger skin surfaces for the treatment of extensive actinic keratoses, sun damage
      P and acne. This article reviews the safety and efficacy of large surface ALA-PDT
      for the treatment of actinic keratoses and photodamage. New data on the
      carcinogenic potential of weekly topical ALA-PDT in mice is also presented.
      Groups of hairless mice were treated weekly with either ALA alone, blue light
      alone or ALA-PDT using blue light for a total of 10 months followed by an
      additional 2 months or observation. Mice were examined weekly for the presence of
      skin tumors. Skin tumors were not observed in mice treated weekly with blue light
      alone, with topical application of ALA alone or with ALA-PDT.

PMID- 14964759
TI  - ALA-PDT and blue light therapy for hidradenitis suppurativa.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, often suppurative skin
      condition which affects primarily apocrine glands. A variety of therapies have
      been used to treat HS, often with unsatisfactory results. Photodynamic therapy
      (PDT), utilizing topical 20% 5-aminolevulinic acid (ALA) is being used to treat a
      variety of dermatologic skin concerns, including photorejuvenation and associated
      actinic keratoses, and acne vulgaris, and other skin tumors. OBJECTIVE: The
      purpose of these case reports is to evaluate the effectiveness of ALA-PDT in
      treating recalcitrant cases of HS. METHODS: Four patients, not responding to
      standard HS therapy, underwent short-contact ALA-PDT therapy utilizing a blue
      light for activation. One to two week intervals between therapies was utilized
      for 3-4 total treatments and follow-up was for 3 months following the last
      treatment. RESULTS: All four of the patients tolerated the therapies well.
      Clinical improvements from 75-100% were noted n 11 of the patients. No adverse
      effects were seen during the treatments. The treatments were pain free and there
      was no downtime associated with these ALA-PDT treatments. CONCLUSIONS: HS is a
      chronic disease which most dermatologists find difficult to treat. The use of ALA
      PDT is finding an ever-expanding role in dermatology. These case studies support
      the use of ALA-PDT in cases of HS. Although all advertising material is expected
      to conform to ethical and medical standards, inclusion in this publication does
      not constitute a guarantee or endorsement by the Journal or its staff of the
      quality or value of such products or of the claims of any manufacturer.

PMID- 14964760
TI  - Effectiveness and safety of ALA-IPL in treating actinic keratoses and
      photodamage.
AB  - BACKGROUND: Photorejuvenation involves the use of a light source or laser in
      reversing the signs of aging. The Intense Pulsed Light (IPL) has demonstrated
      effectiveness in treating signs of photodamage. Photodynamic therapy is a
      relatively new and promising treatment for actinic keratoses. OBJECTIVE: To
      determine the effectiveness of ALA-IPL in treating actinic keratoses as well as
      reversing the signs of aging. METHODS: A retrospective trial of 17 patients
      treated with ALA-IPL. Patients were evaluated for improvement of telangiectasias,
      blotchy pigment, fine wrinkles, coarseness of skin and number of actinic
      keratoses. All side effects were recorded. RESULTS: 68% of actinic keratoses
      resolved after one treatment. There was a 55% improvement in telangiectasias, a
      48% improvement in pigmentary irregularities and a 25% improvement in coarseness
      of skin texture. There was minimal change in fine wrinkle appearance. Side
      effects were minimal including mild erythema and edema for 3-5 days on average.
      No infections were noted. CONCLUSIONS: ALA-IPL treatment is effective in treating
      both actinic keratoses and signs of photodamage. In this study, we achieved
      significant improvement after just one treatment. ALA-IPL is a safe, effective
      way to treat both actinic keratoses and photodamage with little down time.

PMID- 14964761
TI  - Contributions to chronic disease prevention and control: studies among the
      Kivalliq Inuit since 1990.
AB  - A population-based health interview and examination survey of 8 Inuit communities
      in the Kivalliq region of Nunavut, Canada, during the early 1990s has resulted in
      an increased understanding of the burden and extent of cardiovascular diseases
      and diabetes and their risk factors such as genetics, obesity, lipids, blood
      pressure and fatty acids. A recent national health interview survey which
      included a sample from Nunavut indicates that the Inuit still enjoy some
      advantages relative to other Canadians (lower level of self-reported diabetes and
      hypertension) and disadvantages (higher level of smoking, obesity, and heavy
      drinking). The pattern of health and disease among the Inuit is rapidly evolving,
      as the traditional lifestyle becomes further eroded. A long-term prospective
      cohort study that monitors this trend, investigates the etiology, and identifies
      potential interventions is urgently needed.

PMID- 14964762
TI  - Contribution of population surveys to the study of cardiovascular disease and
      diabetes in Greenland.
AB  - Two population surveys with focus on cardiovascular disease and diabetes were
      carried out among the Greenland Inuit in 1993-94 and 1999-2001. The number of
      participants was 264 (1993-94 study) and 2056 (1999-2001 survey) Inuit living in
      Denmark, towns in Greenland, and villages. Compared with the general population
      of Denmark, the Inuit had a high consumption of marine food, but regional and
      demographic variation was marked. Smoking prevalence was high, being
      approximately 70% among adults in 1999-2001. Blood pressure was lower than in
      Denmark and the serum lipid profile was healthier (high HDL cholesterol and low
      triglyceride). The risk factor pattern is consistent with neither an increased,
      nor a decreased cardiovascular risk profile. Longitudinal studies are needed to
      determine the incidence of cardiovascular diseases and diabetes, and to establish
      causal links between traditional risk factors and disease in this non-European
      population.

PMID- 14964763
TI  - Cardiovascular disease among Alaska Natives: a review of the literature.
AB  - BACKGROUND: We reviewed the literature of population-based studies regarding
      heart disease and stroke occurrence among Alaska Natives. The existing literature
      suggests that differences in cardiovascular mortality rates and risk factors
      exist in Alaska Natives by ethnicity and residence. However, data sources are
      largely limited to mortality data and small community-based studies. OBJECTIVES:
      Because cardiovascular disease occurrence has not been well studied among Alaska
      Natives, it is important to avoid sweeping generalizations about the increasing
      or decreasing prevalences of cardiovascular disease and risk factors. RESULTS:
      Recent mortality rates from heart disease (of all types) among Alaska Natives are
      similar to rates for U.S. whites, and mortality rates from stroke among Alaska
      Natives are higher than rates for U.S. whites. Mortality rates from ischemic
      heart disease have been relatively constant among Alaska Natives over the past 20
      years, while over the same time period, rates declined dramatically among U.S.
      Whites. The ischemic heart disease mortality rates among Alaska Native males are
      now comparable to rates among U.S. White males. CONCLUSIONS: Although available
      data indicate no increase in mortality from ischemic heart disease in Alaska
      Natives, the relatively constant death rates over the recent 20 years, compared
      with declining rates elsewhere in the U.S, and the high prevalence of risk
      factors for ischemic heart disease calls for increased descriptive epidemiologic
      studies of the incidence and prevalence of cardiovascular disease outcomes. In
      addition, analytic epidemiologic studies are needed to examine the relationship
      between lifestyle, especially subsistence and traditional lifestyles, and
      cardiovascular disease outcomes.

PMID- 14964764
TI  - Diabetes among Alaska Natives: a review.
AB  - This review summarizes the published information on diabetes mellitus and
      gestational diabetes among Alaska Natives. The most recently published age
      adjusted prevalence was 28.3/1000 in 1998. There is evidence of a steadily
      increasing prevalence, documented both by cross sectional screening studies and
      patient registry methods. The overall incidence rates in 1986-1998 of lower
      extremity amputation (6.1/1000) and renal replacement therapy (2.1/1000) appear
      to be lower than those in other Native American populations in the United States.
      Incidence of stroke and MI in 1986-1998 varied widely by ethnic group and gender
      with Eskimo women having the highest rate of stroke (19.6/1000), and Aleut men
      the highest rate of MI (14/1000). The overall mortality among diabetic Alaska
      Native people in 1986-1993 (43.2/1000) was somewhat lower than that in other US
      diabetic populations, with heart disease being the most common cause of death. A
      high rate of gestational diabetes (6.7%) was reported in one region in 1987-88,
      but this appeared to decline following nutritional education intervention. In
      screening studies, the prevalence of abnormal glucose tolerance has been found to
      be positively associated with body mass index and negatively associated with
      daily seal oil or salmon consumption and higher levels of physical activity.
      Observations on the prevalence and relationships among other factors in the
      insulin resistance syndrome are summarized. Suggestions for prevention of
      diabetes and further studies are presented.

PMID- 14964765
TI  - Post-operative deepvein thrombosis is infrequent in Alaska Natives.
AB  - OBJECTIVES: The expected rate of deep vein thrombosis (DVT) after laparotomy or
      major joint surgery has been reported to be 20 to 50% for unprophylaxed non
      native patients. DVT prophylaxis for surgical patients at the Alaska native
      Medical Center has typically not been offered as the perceived rate of DVT and
      pulmonary embolism in our patient population has been very low. Retrospective
      analysis of positive venous duplex scans at our institution revealed only four
      cases of post-operative DVT during a two-year interval. This study was designed
      to document the actual rate of post-operative DVT in Alaskan natives not provided
      with routine DVT prophylaxis. STUDY DESIGN: Prospective cohort study of DVT in
      open abdominal, open knee, open hip and pelvic fracture surgery patients at the
      Alaska native Medical Center from 1999-2001. METHODS: The day prior to expected
      discharge, we performed venous duplex ultrasonography on 67 patients with open
      abdominal surgery, major open knee or hip surgery, or pelvic fracture who
      received no DVT prophylaxis. Some patients included in the study were also asked
      questions about their consumption of marine mammals and fish, and the native
      blood quanta was estimated in all patients using existing data bases. RESULTS:
      Sixty percent of the study population was determined to be at high risk for DVT
      using standard risk stratification methods. Dietary habits varied widely, but
      were largely reported as being "traditionally" native. Nearly all patients had
      50% or more "native blood". Only one of 67 patients developed a documented post
      operative DVT. CONCLUSIONS: Post-operative deep vein thrombosis in Alaskan
      natives not provided with routine DVT prophylaxis is rare. The data does not
      provide a clear indication as to why Alaskan natives may be at decreased risk for
      post-operative DVT.

PMID- 14964766
TI  - Seasonal variation in hospitalisation for hypertension-related morbidities in
      Sokoto, north-western Nigeria.
AB  - OBJECTIVE: To determine the relationship between hospital admissions of
      hypertension-related morbidities, seasons and meteorological factors in a
      tropical climate. STUDY DESIGN: Retrospective analysis of hospitalised patients
      (440) with hypertension-related morbidities including heart failure (36.4 %),
      stroke (34.8%), chronic renal failure (7.1%) and others (21.7%) from 1995 to
      2000. The relationship between hospital admission, seasons and meteorological
      factors was determined using simple proportions, univariate, multivariate and
      regression analysis. RESULTS: The subjects were aged 21-85 years and represented
      9.3 % of all hypertensives and 7.0% of medical admissions. Mean blood pressure
      was 187.3 +/- 34.0/120 +/- 23 mmHg. Mild, moderate and severe hypertension
      occurred in 30 (6.8%), 59 (13.4%) and 351 (79.8%) patients, respectively. The
      monthly admission rate ranged from 3-11; (mean 6.1 +/- 1.9) patients. Admission
      rates peaked in January/February and August/September, corresponding with the
      peaks of harmattan and the wet seasons, respectively. Mean monthly admission
      rates were significantly higher during harmattan than during the hot season (6.7
      +/- 2 versus 5.2 +/- 1.4 patients; p < 0.05), and during wet season than during
      the hot season (6.4 +/- 1.9 versus 5.2 +/- 1.4 patients; p < 0.05). Considering
      the hypertensives as a whole, a significantly higher proportion of patients was
      hospitalised during the cold season than during the hot season (11% versus 8.2%;
      odds ratio = 1.34). Linear regression analysis showed that hospital admission was
      significantly associated with the monthly minimum temperature (p = 0.02) and
      solar radiation (p = 0.01). Multiple regression analysis revealed that hospital
      admission was also significantly associated with combined meterological factors
      (temperature, radiation, dust haze days and relative humidity) (p = 0.04).
      CONCLUSIONS: Hospital admissions of patients with hypertension-related
      morbidities showed seasonal variation. Appropriate clothing and health planning
      during cold seasons are recommended.

PMID- 14964767
TI  - Revitalization of minority languages as a way to promote well-being in the North.
AB  - BACKGROUND: In this paper I discuss the interdependence between the
      revitalization of minority languages and well-being at the population level.
      OBJECTIVES: The paper aims to describe the history and current status of three
      northern minority languages, Kven, Meankieli and Viena Karelian, and the ways in
      which revitalization of these languages and restoration of their linguistic
      rights could enhance the well-being of the speakers of these languages. METHODS:
      A number of research findings are presented to show that being a minority
      language speaker constitutes an economic, social and health risk. The potential
      psychic and physical adverse effects of linguistic exploitation are also
      discussed. RESULTS: It is further demonstrated in the paper that non-existent
      linguistic rights may have a negative impact, not only on the overall well-being
      of the minority, but also on the group's economic status. Positive findings on
      minority status are presented concerning the speakers of Swedish in Finland and
      the speakers of French in Canada. CONCLUSION: It is also shown that the
      development of a minority language and functional linguistic rights may prolong
      the life expectancy and well-being of the minority members and have a positive
      economic impact, not only on the minority, but also on society as a whole.

PMID- 14964768
TI  - Employment retention of health care providers in frontier areas of Alaska.
AB  - OBJECTIVES: The objectives of this study were to: describe the length of
      employment of health care providers in rural Alaska; assess whether there are
      differences in length of employment among community health aides, medical
      doctors, and nurses; and determine whether provider length of employment is
      significantly increased following implementation of telemedicine. STUDY DESIGN:
      We conducted a prospective cohort study of length of employment among health
      professionals in rural Alaska, and identified the cohort based on current
      employment status of community health aides, medical doctors, and nurses.
      METHODS: Employment data were collected from four Alaska Native regional health
      corporations. Kaplan-Meier product-limit survival analysis was used to assess
      employment length. The Mantel-Haenszel log-rank test was used to test the
      difference between retention (survival) curves among doctors, nurses, and
      community health aides for all four regional health corporations combined. Data
      included provider hire date, termination date, and position title. Fifty seven
      percent of the data points were right-hand censored. RESULTS: The community
      health aides (median (Mdn) = 1186 days) were retained significantly longer than
      either the doctors (Mdn = 596 days), or the nurses (Mdn = 408 days), who were not
      significantly different from each other (log-rank chi2 (2, N = 996) = 68.30, p =
      0.0001). CONCLUSIONS: Our findings document that community health aides in the
      region retain their jobs significantly longer than doctors and nurses. Findings
      highlight the problem of providing an adequate health work force in rural areas.

PMID- 14964769
TI  - Health-check questionnaire for subjects exposed to cold.
AB  - BACKGROUND: Human exposure to cold outdoor and indoor temperatures below 10
      degrees C may be associated with various cold-related sensations and symptoms. It
      is not possible to predict a person's survival ability only by assessing thermal
      environments; but individual screening is always required for good health care
      practice with regards to treatment and/or prevention. METHODS: As part of a
      development project, a health-check questionnaire was developed for the workers
      exposed to cold. The completion of the development was carried out in the
      framework of a Nordic collaboration. RESULTS: This was three-level medical
      screening protocol for detecting individual cold-related health ailments. "The
      health-check questionnaire for subjects exposed to cold" comprises the first step
      of the screening protocol. The medical screening was harmonized with the
      assessment practices for cold-related health risks in the workplaces. CONCLUSION:
      A "health-check questionnaire for subjects exposed to cold" was developed as the
      first step of the three-level medical screening for the detection of cold-related
      health ailments of individuals. The analogical assessment practices for the cold
      related health risks in the workplaces were developed in the same project. They
      both aim towards the establishment of an ISO standard for working in cold
      environments.

PMID- 14964770
TI  - Nordic Society for Arctic Medicine. The effects of cold adaptation on human
      performance.

PMID- 14964771
TI  - Siberian Branch of the Russian Academy of Sciences, Medical Section. Assessment
      of development and progressing mechanisms of arterial hypertension in newly come
      population in the North.

PMID- 14964772
TI  - Danish/Greenlandic Society for Circumpolar Health. 24-hour blood pressure among
      Greenlanders. Influence of diet and life-style.

PMID- 14964773
TI  - American Society for Circumpolar Health. Comparison of mercury in selected
      subsistence foods from western Alaska.

PMID- 14964774
TI  - Coalition launched to boost fight against HIV/AIDS in women. Global alliance will
      focus on raising awareness among women and catalysing action at community level.

PMID- 14964775
TI  - Mechanism of action of volatile anesthetics: role of protein kinase C.
AB  - 1. It is not completely clear how volatile anesthetics cause anesthesia, but one
      possible consequence of their action is to alter presynaptic activity and the
      release of neurotransmitters due to alterations in intracellular signaling. 2.
      Protein kinase C (PKC) is a signal transducing enzyme that is an important
      regulator of multiple physiological processes like neurotransmitter release, ion
      channel activity, and neurotransmitter receptor desensitization. Thus, PKC is an
      attractive molecular target for the synaptic action of general anesthetics. 3.
      However, the effects of these agents on PKC activity are not yet fully understood
      and there are several contradictory data on the literature regarding the in vitro
      and in vivo preparations. 4. Here, we will review some evidence for volatile
      anesthetics effects on neuronal PKC activation.

PMID- 14964776
TI  - Localization of microtubule-associated protein (MAP) 1B in the postsynaptic
      densities of the rat cerebral cortex.
AB  - 1. Although microtubule-associated protein (MAP) 1B and its phosphorylation have
      been suggested to be important for synapse formation among cortical neurons, the
      localization of MAP1B in synapses has not yet been confirmed. In this report, we
      examine the localization of MAP1B in synaptic regions. 2. The localization of
      MAP1B was observed by immunohistochemical and electron microscopic techniques
      using specific antibodies against MAP1B. 3. MAP1B immunoreactivities were widely
      distributed in the cerebral cortex and were observed in the postsynaptic area but
      not in presynaptic terminals. 4. These synapses were classified as the
      asymmetrical type. 5. Only some synapses exhibited MAP1B immunoreactivities.
      MAP1B-immunopositive synapses accounted for about half of the total synapses. 6.
      Such a localization suggests MAP1B's important roles in synaptic functions.

PMID- 14964777
TI  - Thyroid hormone enhances the formation of synapses between cultured neurons of
      rat cerebral cortex.
AB  - 1. Thyroid hormones play important roles in the development of the brain.
      Increasing evidence suggests that the deprivation of thyroid hormones in the
      early developmental stage causes structural and functional deficits in the CNS,
      but the precise mechanism underlying this remains elusive. In this study, we
      investigated the effects of thyroid hormones on synapse formation between
      cultured rat cortical neurons, using a system to estimate functional synapse
      formation in vitro. 2. Exposure to 10(-9) M thyroid hormones, 3,5,3'
      triiodothyronine or thyroxine, caused an increase in the frequency of spontaneous
      synchronous oscillatory changes in intracellular calcium concentration, which
      correlated with the number of synapses formed. 3. The detection of synaptic
      vesicle-associated protein synapsin I by immunocytochemical and immunoblot
      analysis also confirmed that exposure to thyroxine facilitated synapse formation.
      4. The presence of amiodarone, an inhibitor of 5'-deiodinase, or amitrole, a
      herbicide, inhibited the synapse formation in the presence of thyroxine. 5. In
      conclusion, we established a useful in vitro assay system for screening of
      miscellaneous chemicals that might interfere with synapse formation in the
      developing CNS by disrupting the thyroid system.

PMID- 14964778
TI  - Nitric oxide induced heat shock protein 70 mRNA in rat hypothalamus during acute
      restraint stress under sucrose diet.
AB  - 1. Sucrose feeding increases the level of stress-induced heat shock protein 70
      mRNA in the rat hypothalamus. However, the mechanism by which a sucrose diet
      induces mRNA remains unclear. The issues investigated in this study were (1)
      whether a sucrose diet affects nitric oxide production in the hypothalamus, and
      (2) whether nitric oxide mediates the sucrose and stress-induced elevation of
      heat shock protein 70 mRNA. 2. To address the first question, we measured the
      level of nitrate, a final nitric-oxide-oxidation product measurable in vivo,
      using a microdialysis method. To address the second question, we administered a
      nitric oxide synthase inhibitor. NG-nitro-L-arginine methyl ester, prior to
      stress, then measured the mRNA level of heat shock protein 70 by the reverse
      transcription-competitive polymerase chain reaction method. 3. After the
      initiation of restraint stress, rats fed a sucrose-containing diet, unlike those
      fed standard chow, displayed a transient nitrate elevation. This nitrate
      elevation was attenuated by pretreatment with NG-nitro-L-arginine methyl ester.
      The mRNA level increases in rats fed a sucrose diet were dose-dependently
      attenuated by NG-nitro-L-arginine methyl ester. 4. These data suggest that a
      sucrose diet induces heat shock protein 70 under stress by enhancing nitric oxide
      production in the hypothalamus.

PMID- 14964779
TI  - Exocytotic release of [3H]-acetylcholine by ouabain involves intracellular Ca2+
      stores in rat brain cortical slices.
AB  - 1. The effect of ouabain on the release of [3H]acetylcholine ([3H]ACh) in rat
      brain cortical slices was investigated. 2. The ouabain-induced release of [3H]ACh
      was calcium-independent and not blocked by EGTA. 3. BAPTA-AM, a chelator of
      intracellular calcium, inhibited the ouabain effect suggesting the involvement of
      intracellular calcium stores. 4. Vesamicol, a drug that blocks the storage of
      acetylcholine in synaptic vesicles inhibited by 73% the ouabain-induced release
      of [3H] ACh, suggesting exocytotic release of the neurotransmitter. 5. Dantrolene
      and tetracaine, inhibitors of ryanodine and InP3 receptors, inhibited by 57 and
      66% respectively, the ouabain-elicited release of [3H]ACh in brain cortical
      slices. 6. Confocal microscopy and calcium imaging showed that ouabain increased
      the levels of [Ca2+]i in cholinergic SN56 cells and that this increase was
      concentrated in the cell soma. 7. In conclusion, we suggested that ouabain causes
      Ca2+ release from intracellular stores that can increase [3H] ACh exocytosis from
      rat brain cortical slices.

PMID- 14964780
TI  - Effects of altered expression and localization of cyclophilin A on
      differentiation of p19 embryonic carcinoma cells.
AB  - 1. The retinoblastoma susceptibility gene product, p105Rb (RB), is an important
      regulator in the control of cell proliferation, differentiation, and apoptosis.
      Several cellular factors that complex with RB and exert their cellular regulatory
      functions have been identified, such as the RB:cyclophilin A (CypA) complex. 2.
      CypA is a cytoplasmic immunophilin and known for its involvement in T-cell
      differentiation and proliferation. Although CypA has a pivotal role in the immune
      response, its function in other signaling pathways is largely unknown. 3. In this
      study, we used a model of neuronal differentiation to demonstrate that the
      nuclear translocation of CypA, the appearance of hypophosphorylated RB and the
      enhancement of RB: CypA complex formation correlates with retinoic acid induced
      neuronal differentiation. 4. Inhibition of CypA expression results in repression
      of both the hypophosphorylated RB and the neuron-specific differentiation marker,
      class III beta tubulin. 5. The evidence of enriched CypA and colocalization of RB
      with CypA in the nucleus of primary adult sensory neurons substantiated the
      important event of RB-mediated neuronal differentiation of p19 EC cells.

PMID- 14964781
TI  - Levels of Bcl-2 and P53 are altered in superior frontal and cerebellar cortices
      of autistic subjects.
AB  - 1. Autistic disease (AD) is a severe neuropsychiatric disorder affecting 2-4
      children per 10,000. We have recently shown reduction of Bcl-2 and increase in
      P53, two important markers of apoptosis, in parietal cortex of autistic subjects.
      2. We hypothesized that brain levels of Bcl-2 and P53 would also be altered in
      superior frontal cortex and cerebellum of age-, sex, and postmortem-interval
      (PMI)-matched autistic subjects (N = 5 autistic, N = 4 controls). 3. Brain
      extracts were prepared from superior frontal cortex and cerebellum and subjected
      to Western blotting. 4. Results showed that levels of Bcl-2 decreased by 38% and
      36% in autistic superior frontal and cerebellar cortices, respectively when
      compared to control tissues. By the same token, levels of P53 increased by 67.5%
      and 38% in the same brain areas in autistic subjects vs. controls respectively.
      Calculations of ratios of Bcl-2/P53 values also decreased by 75% and 43% in
      autistic frontal and cerebellar cortices vs. controls respectively. The autistic
      cerebellar values were significantly reduced (p < 0.08) vs. control only. There
      were no significant differences in levels of beta-actin between the two groups.
      Additionally, there were no correlations between Bcl-2, P53, and beta-actin
      concentrations vs. age or PMI in either group. 5. These results confirm and
      extend previous data that levels of Bcl-2 and P53 are altered in three important
      brain tissues, i.e. frontal, parietal, and cerebellar cortices of autistic
      subjects, alluding to deranged apoptotic mechanisms in autism.

PMID- 14964782
TI  - Long-term imipramine treatment increases nitrate levels in the rat hypothalamus.
AB  - 1. Animal experiments have shown nitric oxide synthase inhibitors to have
      antidepressant-like properties. However, the effects of clinically available
      antidepressants on nitric oxide production in the brain remain unclear. In the
      present study, we examined whether imipramine, a conventional antidepressant,
      changes the levels of type-II nitric oxide synthase mRNA and nitrate, a final
      nitric-oxide-oxidation product measurable in vivo, in the rat brain. 2. Type-II
      nitric oxide synthase mRNA was detected using a reverse transcription-polymerase
      chain reaction method and nitrate was measured with a combination of high
      performance liquid chromatography and the Griess reaction. 3. In untreated rats,
      type-II nitric oxide synthase mRNA was not detected in the hypothalamus,
      hippocampus, cerebral cortex, brain stem, or cerebellum. However, after 28-day
      oral administration of imipramine, it was detected in every brain region tested.
      Nitrate levels in the hypothalamus and cerebral cortex increased after 28-day
      treatment. In the hypothalamus, nitrate levels increased dose-dependently. These
      dose-dependent nitrate level changes were prevented by pretreatment with a nitric
      oxide synthase inhibitor. Moreover, the preventive effect of NG-nitro-L-arginine
      methyl ester was reversed by coadministration of L-arginine, a nitric oxide
      substrate. 4. These results suggest that chronic imipramine treatment induces
      nitric oxide synthase gene expression in the brain, followed by augmented NO
      production.

PMID- 14964783
TI  - Artificial neural networks: non-linear QSAR studies of HEPT derivatives as HIV-1
      reverse transcriptase inhibitors.
AB  - Structure-anti HIV activity relationships were established for a sample of 80 1
      [2-hydroxyethoxy-methyl]-6-(phenylthio)thymine (HEPT) using a three-layer neural
      network (NN). Eight structural descriptors and physicochemical variables were
      used to characterize the HEPT derivatives under study. The network's architecture
      and parameters were optimized in order to obtain good results. All the NN
      architectures were able to establish a satisfactory relationship between the
      molecular descriptors and the anti-HIV activity. NN proved to give better results
      than other models in the literature. NN have been shown to be particularly
      successful in their ability to identify non-linear relationships.

PMID- 14964784
TI  - Novel magnetic supports for small molecule affinity capture of proteins for use
      in proteomics.
AB  - Magnetic supports are tested for use in batch affinity capture of proteins. Two
      types of magnetic polymer composites were used for solid phase synthesis and for
      the batch affinity chromatography of folate binding protein from a protein
      mixture. Gly-Gly-L-Methotrexate as well as other analogs were synthesized on
      magnetic supports consisting of either polyoxyalkyleneamine grafted onto
      polystyrene beads or a copolymer of polyethylene glycol dimethylacrylamide
      (PEGA). Both supports incorporated within their matrix sub-micron particles of
      paramagnetic magnetite. The peptide-methotrexate analogs were attached to the
      magnetic supports via a photocleavable linker. The bound methotrexate-peptide
      analogs were equilibrated with a protein mixture consisting of bovine albumin,
      chicken albumin, folate binding protein, lysozyme, lactoferrin and
      lactoperoxidase precursor in phosphate buffered saline (PBS) and then after
      magnetically separating and washing the supports of any unbound components the
      bound protein was removed either through the photocleavage of the tethered
      methotrexate-peptide ligand or via exchange with soluble methotrexate. In all
      cases, the photocleavage or exchange with soluble methotrexate released folate
      binding protein as the major affinity captured protein. Of the two magnetic
      supports tested, the PEGA based support was found to be superior to the
      polyoxyalkyleneamine grafted polystyrene support and comparable to beaded agarose
      in releasing bound folate binding protein. Of the two methods for removing bound
      protein, photocleavage of the covalently attached ligand was found to release
      exclusively folate binding protein as opposed to exchange with soluble
      methotrexate which released residual amounts of the non-specifically bound
      proteins bovine and chicken albumin, in addition to folate binding protein. Thus,
      use of the PEGA based magnetic support in conjunction with a photocleavable
      linker should help facilitate the automation of multiple parallel affinity
      chromatography for proteomics applications.

PMID- 14964785
TI  - Creating molecular diversity from antioxidants in Brazilian propolis. Combination
      of TOPS-MODE QSAR and virtual structure generation.
AB  - A QSAR model for antioxidative activity based on the Sub-Structural Molecular
      Design (TOPS-MODE) approach is developed for a series of compounds present in
      Brazilian propolis. This approach permitted the structural interpretation of the
      antioxidative activity of these compounds in terms of bond contributions. By
      these means we have identified the structural groups and regions that contribute
      to the antioxidative activity of the cinnamic acid and flavonoid derivatives
      present in the propolis. These results were then used to identify the positions
      and substituents to be used in a virtual compound generation experiment. Using
      this approach a total of 327 compounds were generated from which more than 70 are
      predicted to be more active than the most powerful antioxidants in the Brazilian
      propolis. From these 70 compounds less than 20 have been reported in the
      literature. Consequently, a high proportion of novel compounds with potential
      antioxidative activity has been identified by the current approach. This
      contributes to enhance the molecular diversity of the analogues of Brazilian
      propolis compounds with antioxidative properties.

PMID- 14964786
TI  - Effective combinatorial strategy to increase affinity of carbohydrate binding by
      peptides.
AB  - The Thomsen-Friedenreich antigen, a carcinoma-associated disaccharide involved in
      carcinoma cell homotypic aggregation and increased metastatic potential, has
      clinical value as a prognostic indicator and a marker of metastasized cells.
      Hence, it can reasonably be predicted that antigen-binding macromolecules are
      valuable clinical in vivo diagnostic/therapeutic targeting agents. Recently, we
      have selected first-generation antigen-binding peptides from a random peptide
      bacteriophage display library and have applied combinatorial affinity maturation
      to select functionally-maturated peptides, which target cultured carcinoma cells
      and inhibit carcinoma cell aggregation. In the current study we hypothesize that
      a targeted search of sequence space surrounding the antigen-binding consensus
      sequence will select unpredictable amino acid sequences in the non-consensus
      portions of the peptides, leading to increased affinity for the carbohydrate and
      greater solubility in physiological buffers. This comprehensive in vitro analysis
      demonstrates that preferential evolution of the amino-terminal sequence of the
      peptides occurred, which correlated, in structure/function studies, with the
      acquisition of maturated function. The maturated peptides are more soluble than
      the earlier peptides. Studies of peptide binding to the disaccharide indicate
      that two maturated peptides (P-30-1, F03) have higher affinity for the antigen
      and bind with higher intensity to the surface of cultured human carcinoma cells
      than the first-generation peptides. The results support our hypothesis that
      affinity maturation can improve carbohydrate binding by peptides and have
      theoretical importance as the first report of maturation of carbohydrate-binding
      affinity in a small, soluble peptide.

PMID- 14964787
TI  - Medical litigation: past, present and future.

PMID- 14964788
TI  - Atrial myxomas: diagnosis and management.

PMID- 14964789
TI  - Computed tomography of the brain: a pictorial review.
AB  - This pictorial review briefly describes the basic principles of computed
      tomography scanning of the brain. A series of commonly encountered intracranial
      pathologies is then reviewed.

PMID- 14964790
TI  - The hand X-ray in rheumatology.
AB  - X-ray of the hands is the most valuable imaging modality in rheumatology. Joint
      disease may be identified by individual features such as joint space narrowing,
      erosions, new bone formation, subluxation and deformity, which may be diagnostic.
      In diseases such as rheumatoid arthritis presence of erosions on hand X-ray give
      a valuable measure of disease progression and response to therapy.

PMID- 14964791
TI  - Imaging of testicular tumours.
AB  - This article reviews the diagnosis, pathology and imaging of testicular tumours,
      predominantly germ cell tumours. It will discuss the imaging techniques used in
      their diagnosis, staging and surveillance.

PMID- 14964792
TI  - Cirrhotic ascites: a review of management.
AB  - Ascites is a common and debilitating complication of cirrhosis where optimizing
      management can have satisfying results. New therapeutic and interventional
      developments have demonstrated improved outcomes. These are reviewed and
      integrated with established management techniques including consideration of
      liver transplantation.

PMID- 14964793
TI  - Management of oral and maxillofacial infection.
AB  - Maxillofacial infections are common but can potentially be life threatening.
      Accurate diagnosis is essential to prevent mismanagement with potential severe
      consequences. This article discusses the aetiology, differential diagnosis, host
      response, spread of infection and treatment.

PMID- 14964794
TI  - Walking problems in young children.
AB  - This article attempts to define normal development throughout childhood and
      provide straightforward advice in the physical assessment of the child in this
      situation. It also attempts to outline the groups of conditions that lead to
      walking abnormalities and highlight the salient physical features and special
      investigations that are required to make these diagnoses with confidence.

PMID- 14964795
TI  - Preserving vision with verteporfin photodynamic therapy.
AB  - Wet age-related macular degeneration (AMD) is the leading cause of blindness in
      the elderly population. Verteporfin photodynamic therapy (PDT) is significantly
      effective in preventing visual loss in patients with subfoveal choroidal
      neovascularization caused by exudative AMD. This article reviews verteporfin PDT
      and discusses treatment and evolving appraisal guidance.

PMID- 14964796
TI  - Performance review procedures for the preregistration year: a map through the
      minefield.
AB  - When a case of underperformance occurs, it can be a stressful event for both the
      educational supervisor and the trainee. This article explains the procedures for
      managing underperformance of preregistration house officers, developed by the
      North Western Deanery.

PMID- 14964797
TI  - Non-traumatic coma.

PMID- 14964798
TI  - Health-care practitioners.

PMID- 14964799
TI  - Health-care practitioners.

PMID- 14964800
TI  - Health-care practitioners.

PMID- 14964801
TI  - A vascular left atrial myxoma causing obstructive symptoms.

PMID- 14964802
TI  - Cerebral venous thrombosis presenting as unilateral headache and visual blurring
      in a man with nephrotic syndrome.

PMID- 14964803
TI  - Atrial myxoma: a cardiocutaneous syndrome.

PMID- 14964804
TI  - Epidurals and clopidogrel in peripheral vascular surgery.

PMID- 14964805
TI  - A systematic overview of published antimalarial drug trials.
AB  - Systematic database searches identified 435 antimalarial drug treatment trials,
      involving 82,616 patients, conducted and published between 1966 and December
      2002. Of these trials 72% were randomised; 64 (15%) trials involved severe
      malaria, 47 (11%) studied Plasmodium vivax, 3 Plasmodium malariae or Plasmodium
      ovale, and the remainder (74%) assessed treatment responses in uncomplicated
      falciparum malaria. Twelve trials (2.7%) specifically evaluated antimalarial
      treatments in pregnant women. Overall 49% of trials were conducted in Asia (29%
      from Thailand alone) and 42% in Africa. Half of all the patients studied had been
      in trials published in the past 7 years. There has been a recent rise in the
      proportion of trial enrolling children, and a tripling in the average number of
      patients recruited per trial (from approximately 100 in the 1970s to 300
      currently). Chloroquine was given to over half the patients in antimalarial drug
      trials (n = 53552) compared with artemisinin derivatives (n = 12463), mefloquine
      sulphadoxine-pyrimethamine (n = 9153), mefloquine (n = 5546) and sulphadoxine
      pyrimethamine (n = 5909). The quality of safety and efficacy data for recently
      evaluated drugs contrasts with a relative paucity of data for older 'established'
      compounds.

PMID- 14964806
TI  - The potential for West Nile virus to establish outside of its natural range: a
      consideration of potential mosquito vectors in the United Kingdom.
AB  - Outbreaks of West Nile virus (WNV) infection have occurred sporadically in
      Europe, apparently due to the migration of infected birds and the subsequent
      establishment of a transmission cycle involving culicine and anopheline
      mosquitoes. Both human and equine species become infected, but are considered as
      dead end hosts since they play an insignificant role in the maintenance of the
      cycle. Following the introduction of WNV into the United States in 1999 it is
      increasingly apparent that the virus has an extraordinary ability to infect a
      very broad range of arthropod species. Here we consider the potential for British
      mosquitoes to transmit WNV in the event that it is introduced into the UK.

PMID- 14964807
TI  - Amoebiasis distribution in the past: first steps using an immunoassay technique.
AB  - The identification of parasites in ancient human faeces is compromised by
      differential preservation of identifiable parasite structures. However, protein
      molecules can survive the damage of the environment and can be detected even
      after centuries. In this paper it is shown that is possible to detect copro
      antigen of Entamoeba histolytica in historic and prehistoric human faecal
      remains, using a commercially available enzyme immunoassay (ELISA) kit. The kit
      uses monoclonal antibody-peroxidase conjugate specific for E. histolytica
      adhesin. A total of 90 specimens of desiccated faeces found in mummies and
      ancient organic sediment from South America, North America, Africa, and Europe
      were examined. The ELISA detected 20 positive samples, dated to about 5300 years
      before present to the 19th Century ad. The positive samples are from
      archaeological sites in Argentina, USA, France, Belgium, and Switzerland. The
      detection of protozoan antigen using immunoassays is a reliable tool for the
      studies of intestinal parasites in the past.

PMID- 14964808
TI  - Lack of technical specificity in the molecular diagnosis of toxoplasmosis.
AB  - The polymerase chain reaction amplification of a fragment of the B1 gene of
      Toxoplasma gondii coupled to hybridization was performed in 42 patients from Rio
      de Janeiro, Brazil. The results showed 50% of positivity in the IgM positive
      toxoplasmosis group, and 12.5% in the positive IgG and negative IgM individuals.
      The data presented here revealed a lack of specificity of the molecular approach,
      clearly indicating that the primers used may co-amplify human sequences.

PMID- 14964809
TI  - Taiwan's venomous snakebite: epidemiological, evolution and geographic
      differences.
AB  - Located at the juncture of tropical and subtropical regions, Taiwan has a warm
      and humid climate with abundant precipitation and food, which coupled with the
      island's diverse vegetation and landscape, makes it a suitable environment for
      many snake species. Among these, Naja atra, Bungarus multicinctus,
      Deinagkistrodon acutus, Trimeresurus mucrosquamatus, Trimeresurus stejnegeri,
      Daboia russelii siamensis are the 6 principal venomous species, and have caused
      significant injuries and death over the years. The natural environment of Taiwan
      has changed tremendously in the last 20-30 years, which is likely to have
      affected the number and distribution of venomous snakes, thus indirectly
      affecting incidence of snakebite. A retrospective analysis of 286 snakebite cases
      at a medical center in central Taiwan analyzed the snakebite-related
      epidemiological data in the past 30 years. The results showed that the bite rates
      of various venomous snakes vary geographically, which is related to the
      overlapping of the human living environment and snakes' habitat. In Taiwan, T.
      mucrosquamatus and T. stejnegeri bites are most common. Bites by Deinagkistrodon
      acutus and Daboia russelii siamensis generally occur in the south and east parts
      of the island and attacks by Naja atra are most common in central Taiwan.
      Aggressive antivenom treatment can reduce snakebite mortality rate, but for
      Bungarus multicinctus bites, maintaining the patient's airway and supporting
      their ventilation is vital to reducing mortality rate in addition to antivenom
      treatment.

PMID- 14964810
TI  - Detection of Leishmania infantum cryptic infection in asymptomatic blood donors
      living in an endemic area (Eivissa, Balearic Islands, Spain) by different
      diagnostic methods.
AB  - The extent of cryptic leishmaniasis in blood donors from a Spanish endemic area,
      (Eivissa Island) was studied using various immunological and parasitological
      methods. Sera from 656 blood donors were analysed: 16 (2.4%) were positive by
      ELISA and 50 (7.6%) by Western blot. Peripheral blood mononuclear cells (PBMC)
      and buffy coat (BC) samples, were analyzed by culture and nested-PCR. DNA of L.
      infantum was amplified in 27 (22.1%) of 122 PBMC. Parasites were isolated in 3
      (4.5%) of 67 BC cultures and the strains were identified as L. infantum zymodeme
      MON-28. No parasites were isolated in PBMC culture. After 12 months, a second
      blood sample was obtained from 18 blood donors who were positive by nested-PCR in
      the first extraction; nine of them remained positive. Delayed type
      hypersensitivity (DTH) tests on 15/67 donors (22.3%) were positive. Comparison of
      results obtained by ELISA, WB and DTH; ELISA, WB and nested-PCR and nested-PCR
      and BC culture showed a significant association (Pearson test, P < 0.05). L.
      infantum zyodeme MON-28 was identified in three strains isolated from
      asymptomatic donors, which suggests a low virulence capacity of these strains.
      The detection of Leishmania DNA in a high number of asymptomatic subjects
      supports the need to monitor it in blood donors endemic areas.

PMID- 14964811
TI  - The management of fevers in Kenyan children and adults in an area of seasonal
      malaria transmission.
AB  - This study investigates the source, timing and types of treatment for fevers
      across all ages in a low malaria-transmission area of Kenya. The period
      prevalence for fever, and subsequent treatment seeking behaviour, was similar
      across all ages. The use of the informal retail sector was common (47% of first
      actions), though most visits to shops and chemists (77%) resulted in treatment
      with an antipyretic not an antimalarial. The major source of the first line
      recommended drug, sulfadoxine-pyrimethamine (SP), was at the formal health
      sector, and 32% of fevers made at least one visit to a health care facility.
      Although only 7% of fevers received SP within 24 hours of fever onset, 27%
      ultimately received treatment with this antimalaria. It is estimated that of the
      total amount of SP consumed in this population, only 20% is administered to
      children less than 5 years old. In this area of Kenya disease risks decline with
      increasing age, however, adult populations consume over 40% of prescribed or
      purchased anti-malarial drugs. In light of the proposed new, more costly anti
      malarial drug combinations these findings have major implications for the
      effective allocation of limited financial resources at household and government
      levels.

PMID- 14964812
TI  - The influence of climate on the epidemiology of bartonellosis in Ancash, Peru.
AB  - The aim of this study was to evaluate the association between bartonellosis and
      selected climatic factors during the time periods 1983-1988 and 1995-99, which
      included two events of the El Nino phenomenon (1986-88, 1997-98), and to identify
      a reliable climate parameter to be used as an alert indicator for bartonellosis
      outbreaks in Ancash. The study site was Ancash and its province Carhuaz, Peru.
      Time-series cross-correlation analysis was used to assess the association between
      bartonellosis and climate parameters. A higher, almost 4-fold, monthly
      bartonellosis incidence risk in Ancash department was observed during the El Nino
      events of 1986-88 and 1997-98. At a regional (Ancash department) and local level
      (Carhuaz, Ancash), the best correlation was observed between bartonellosis and
      sea-surface temperature (SST). The results indicate that SST would be the best
      climate parameter to be used as an alert indicator for bartonellosis outbreaks in
      Ancash.

PMID- 14964813
TI  - Hepatosplenic morbidity in two neighbouring communities in Uganda with high
      levels of Schistosoma mansoni infection but very different durations of
      residence.
AB  - Peri-portal fibrosis can be a serious sequelae of Schistosoma mansoni infection.
      Age or duration of exposure have been identified as important risk factors, but
      their relative importance cannot be easily separated. Here, we have compared two
      cohorts, aged 6-50 years and resident for ten years or since birth, from two
      neighbouring villages (Booma and Bugoigo) on the eastern shore of Lake Albert,
      Uganda. Parasitological measurements were similar, whereas the prevalence of peri
      portal fibrosis was 5-fold higher in Booma. Data from the cohorts were pooled to
      assess the relative contribution of age and duration of residency on the risk of
      disease. Amongst adults, duration of residency was the critical risk factor-
      individuals aged 17-31 years resident for more 22 years had an almost 12-fold
      increased risk of fibrosis than those resident for less than 15 years. Height
      standardised Splenic Vein Diameter (SVD), Portal Vein Diameter (PVD), Para
      sternal Liver Length (PLL) and Spleen Length (SL) values were all higher in
      Booma, and each organometric parameter except PLL increased with the severity of
      fibrosis. Our results clearly demonstrate that duration of exposure is a critical
      risk factor for the development of peri-portal fibrosis and its sequelae in
      adults. This parameter should therefore be a routine measurement during
      epidemiological surveys of S. mansoni.

PMID- 14964814
TI  - Reiterative justice?

PMID- 14964815
TI  - A rational approach to the principles and practice of crime scene investigation:
      I. Principles.
AB  - This paper proposes a structured approach to crime scene investigation that may
      be applied to the wider aspects of criminal investigation. The approach is an
      adaptation of the hypotheticodeductive method. The investigator begins with
      observation of the scene leading to a cycle of hypotheses creation and testing
      with other information being supplied only after the initial scene examination
      and hypotheses creation. The recording of observation, hypotheses creation and
      testing, and information received creates an audit trail of the investigative
      process. The method seeks to minimise observer bias by providing a rational and
      recorded approach to crime scene investigation.

PMID- 14964816
TI  - The viability and possible applications of high resolution mark replicator
      casting compound in document examination.
AB  - Mark replicator casting compounds are commonly associated with recovering
      toolmark detail. A series of experiments was designed to identify the possible
      applications, and assess the overall viability, of using mark replicator compound
      to record indentations on questioned documents. The trials included testing the
      effect of Isomark High Resolution Mark Replicator on different paper-based
      substrate types, and observing in particular, any damage that it may cause. The
      experiments also tested the effect that the mark replicator has on subsequent
      fingerprinting techniques. It was found that the mark replicator successfully
      recorded indentations on paper and card surfaces. In some cases, the mark
      replicator caused staining on some of the surfaces and had a negative effect on
      the quality of fingerprints subsequently developed.

PMID- 14964817
TI  - A single approach to the recovery of DNA and firearm discharge residue evidence.
AB  - The Laboratory of the Strathclyde Police Forensic Support Department extracts DNA
      from cellular material recovered from garments submitted as evidence. The
      standard method used an adhesive tape attached to a plastic or acetate support.
      This paper demonstrates a method whereby a single sample, recovered from
      clothing, can be examined for Firearm Discharge Residue and then extracted for
      DNA.

PMID- 14964818
TI  - Multi-technique comparison of source and primary transfer soil samples: an
      experimental investigation.
AB  - The comparison of soil samples is of long-standing and increasing interest in
      forensic science. Routine comparisons should involve the use of several
      techniques in combination. A wide range of analytical techniques can be used,
      choice being dependent on several factors including sample size and character,
      time constraints and cost limitations. In this paper results are presented for
      experiments carried out to test the effectiveness of four of the available
      analytical techniques (spectro-photometric colour determination, laser
      diffraction particle size analysis, stable isotope analysis and chemical element
      analysis) used to compare single source and primary transfer soil samples. Four
      soil types and five footwear types were used. All four techniques showed
      excellent precision and good resolving power between soil types. Only relatively
      small differences were obtained between source and transferred soil samples in
      terms of colour, stable carbon and nitrogen isotope ratios and elemental
      chemistry. Slight but significant differences were found in grain size,
      indicating that the primary transfer process is to some extent grain size
      selective.

PMID- 14964819
TI  - Automatic forensic face recognition from digital images.
AB  - Digital image evidence is now widely available from criminal investigations and
      surveillance operations, often captured by security and surveillance CCTV. This
      has resulted in a growing demand from law enforcement agencies for automatic
      person-recognition based on image data. In forensic science, a fundamental
      requirement for such automatic face recognition is to evaluate the weight that
      can justifiably be attached to this recognition evidence in a scientific
      framework. This paper describes a pilot study carried out by the Forensic Science
      Service (UK) which explores the use of digital facial images in forensic
      investigation. For the purpose of the experiment a specific software package was
      chosen (Image Metrics Optasia). The paper does not describe the techniques used
      by the software to reach its decision of probabilistic matches to facial images,
      but accepts the output of the software as though it were a 'black box'. In this
      way, the paper lays a foundation for how face recognition systems can be compared
      in a forensic framework. The aim of the paper is to explore how reliably and
      under what conditions digital facial images can be presented in evidence.

PMID- 14964821
TI  - Silicon pathology?

PMID- 14964820
TI  - Rainfall and temperature effects on the decomposition rate of exposed neonatal
      remains.
AB  - There are scarce data describing seasonal effects on decomposition, and on the
      decomposition of neonatal remains. Piglet carcasses were exposed in a forest at
      Coranderrk Bushland (Victoria, Australia) each season for two years. The effects
      of season, year, temperature, and rainfall on mass loss rate and decay stage
      durations were investigated. There was a significant season and year interaction
      in weeks taken until the end of putrefaction: this was longest in winter,
      followed by autumn, spring and summer. Higher temperatures and rainfall increased
      both mass loss rates, and decomposition stage progression rates.

PMID- 14964823
TI  - The cutting edge.

PMID- 14964822
TI  - An assessment of whether SNPs will replace STRs in national DNA databases--joint
      considerations of the DNA working group of the European Network of Forensic
      Science Institutes (ENFSI) and the Scientific Working Group on DNA Analysis
      Methods (SWGDAM).

PMID- 14964824
TI  - [Molecular AFLP-marking of genotypes of pepper (Capsicum annuum) cultivars].
AB  - The results of AFLP study of 14 Capsicum annuum cultivars are presented.
      Notwithstanding the known low genomic variation of large-fruited sweet pepper,
      AFLP analysis proved to be suitable for detecting polymorphism and genotyping
      pepper cultivars. Nine primer pairs were selected to allow identification of the
      cultivars under study. Among-cultivar polymorphism detectable with these primers
      was estimated at 16.5%. A characteristic AFLP pattern was obtained for each
      cultivar. Several cultivar-specific fragments were revealed for seven cultivars.
      On the basis of the AFLP data, genetic distances between cultivars were computed
      and a tree was constructed by means of hierarchic cluster analysis (UPGMA) with
      the Jacquard coefficient. It was assumed that this information is useful in
      breeding programs involving the cultivars examined.

PMID- 14964825
TI  - [Microevolution of nodule bacteria in emergence of mutants with changed viability
      in the "plant-soil" system].
AB  - Simulation of cyclic processes in the plant-soil system was used to analyze the
      effects of factors responsible for the population dynamics of rhizobia on
      generation of mutants with changed ex planta viability. Rhizobial evolution in a
      system of ecological niches (soil, rhizosphere, nodules) was described with
      recurrent equations. Computer experiments were carried out with parameters
      determining the mutation pressure, selection, and amplitude of the population
      wave arising in soil on the release of bacteria from nodules and the rhizosphere.
      Analysis of the model showed that (1) mutants with enhanced ex planta viability
      do not completely replace the parental strain and (2) mutants with impaired ex
      planta viability may be fixed in the population. The maintenance of genotypes
      subject to elimination from the soil and rhizosphere by Darwinian selection was
      associated with frequency-dependent selection (FDS), which is effective in
      competition for nodulation. The FDS index was proposed to characterize FDS
      pressure and was shown to determine the population polymorphism for adaptive
      traits. An increase in population wave amplitude proved to increase the fixation
      level (the proportion in the limiting state of the system) of mutants with
      enhanced viability and to decrease it in mutants with low viability. The results
      obtained with the model agreed with the data that, in edaphic stress, rhizobial
      populations remain highly polymorphic, which is associated with the maintenance
      of sensitive strains. The simulation procedure may be employed in estimating the
      genetic consequences of introduction of modified rhizobial strains in the
      environment.

PMID- 14964826
TI  - [Application of pM3, a broad host range IncP-9 plasmid, for genetic analysis in
      Enterobacteriaceae].
AB  - The possibility of using a transposon-carrying variant of broad host range
      plasmid pM3 (IncP-9) as a universal vector for transposon mutagenesis and as a
      chromosome-mobilizing factor was demonstrated in bacteria of the family
      Enterobacteriaceae.

PMID- 14964827
TI  - Molecular markers (RAPD) associated with growth, yield and origin of the
      silkworm, Bombyx mori L. in India.
AB  - To identify the molecular markers associated with growth and yield parameters in
      silkworm, Bombyx mori, RAPD profiles generated with seven UBC primers for
      fourteen silkworm stocks, originated from China, Japan, India and Russia, were
      statistically analyzed. Stepwise Multiple Regression Analysis establishes
      significant association of 45 markers with larval span, growth indices and four
      cocoon yield parameters relevant for silk production and t-test attest
      significance of the association of 89.5(1500 bp) and 54.13(300 bp), respectively
      with longer larval duration and high cocoon weight. The validity of this
      selection of markers was further supported with Discriminant Function Analysis
      (DFA) done on the basis of Mahalanobis D2 statistics. The two indices of
      yield/growth were also tested with DFA, which helped in identifying a few markers
      and thereby opened scope of using such marker (e.g. 91.11(900 bp)) for
      incorporating molecular markers in the breeding program for crop improvement in
      silkworm.

PMID- 14964828
TI  - [Multiple allelism of the net gene in Drosophila melanogaster and Drosophila
      simulans].
AB  - The net gene mutations are known to cause abnormal pattern of veining in all wing
      regions except for the first posterior cells. In natural populations of
      Drosophila melanogaster, the net alleles were identified, which differ in
      phenotypic expression from standard mutations. The mutants net-extra-analis from
      a population Belokurikha-2000 have only a single additional vein in the third
      posterior cell. A line from Chernobyl-1986 population have another nontypical
      allele netCh86 and shows a lower degree of abnormalities than that usually
      observed. About 10% of these flies have an additional vein fragment in the first
      posterior cell. In both males and females of D. simulans population Tashkent
      2001, which exhibit netST91 mutation, a net of additional veins is formed as a
      specific additional fragment in the first posterior cell. The pattern of veining
      conferred by alleles net-extra-analis and netCh86 is altered to a lesser extent;
      these alleles are dominant with respect to alleles net2-45 and netST91, which
      cause more abnormalities. The heterozygotes for alleles netST9 and netCh86 and
      for Df(2) net62 deletion have an additional fragment in the first posterior cell
      and show similarly strong deviations from normal wing vein pattern. The natural
      net alleles correspond, presumably, to different molecular gene defects involved
      into uncertain local interactions with numerous modifying factors and other genes
      that specify the wing vein pattern.

PMID- 14964829
TI  - [Differentiation of activity of a superoxide dismutase inhibitor in human cells
      exposed to radiation, chemical mutagens and radioadaptive response].
AB  - The superoxide dismutase (SOD) inhibitor, TRIEN, which enhanced the formation of
      gamma-induced DNA breaks in cells of healthy donors and patients with Marfan
      syndrome and Bloom syndrome (repair-defective hereditary diseases), had virtually
      no effect on the formation of radioadaptive response (RAR) in these systems.
      Similar results were obtained in studies on cell survival: TRIEN facilitated
      mortality in cells irradiated with gamma-rays but did not affect RAR formation.
      TRIEN also increased the deleterious effect of CdCl2, which indicates that SOD
      apparently plays a certain role in cell defence against this mutagen.

PMID- 14964830
TI  - [Effect of the yellow locus on sensitivity of drosophila sex cells to chemical
      mutagens].
AB  - The effect of the yellow (y) locus on germ cell sensitivity to the alkylating
      agent ethyl methanesulfonate (EMS) has been studied in Drosophila. Since DNA
      repair is one of the most important factors that control cell sensitivity to
      mutagens, the approaches used in our experiments aimed at evaluating the
      relationship between germ-cell mutability and activity of DNA repair. Germ-cell
      mutability and repair activity were assessed using several parameters, the most
      important of which was the frequency of the recessive sex-linked lethal mutations
      (RSLLM). In one series of experiments, the adult males of various genotypes
      (Berlin wild; y; y ct v; y mei-9a) were treated by mutagenic agents and then
      crossed to Basc females. Comparative analysis of germ-cell mutability as
      dependent on genotype and the stage of spermatogenesis showed that the yellow
      mutation significantly enhanced the premeiotic cell sensitivity to EMS,
      presumably, due to the effect on DNA repair. In the second series of experiments,
      the effect of the maternal DNA repair was studied and, accordingly, mutagen
      treated Basc males were crossed to females of various genotypes including y and y
      mei-9a ones. The crosses involving y females yielded F1 progeny with high
      spontaneous lethality, whereas in F2, the frequency of spontaneous mutations was
      twice higher. The germ cell response to EMS depended also on female genotype: the
      effect of yellow resulted in increased embryonic and postembryonic lethality,
      whereas the RSLLM frequency decreased insignificantly. The latter result may be
      explained by elimination of some mutations due to 50% mortality of the progeny.
      The results obtained using the above two approaches suggest that the yellow locus
      has a pleiotropic effect on the DNA repair systems in both males and females of
      Drosophila.

PMID- 14964831
TI  - [Characteristics of radish lines and hybrids from the spectrum of multiple
      molecular forms of enzymes].
AB  - We characterized radish lines from a genetic collection on the basis of six
      enzyme systems, identified genes controlling these enzymes, and examined joint
      inheritance of some biochemical and morphological traits.

PMID- 14964832
TI  - [Genetic analysis of the duration of the vegetative period in cotton Gossypium
      hirsutum L. with background of various nitrogen level in soil].
AB  - Using Hayman's model of genetic analysis of the F1 hybrids from crosses between
      early- and late-ripening forms of cotton Gossypium hirsutum L., we examined
      inheritance of the duration of vegetative period at various contents of nitrogen
      in soil. Two variants of hybrid plants were studied. With the natural content of
      soil nitrogen, incomplete directionally dominance of earliness over late ripening
      with prevalence of additive gene effect of nonallelic interactions was observed.
      The genetic formulas of this trait proved to change with varying nitrogen
      nutrition.

PMID- 14964833
TI  - [Effect of substituting chromosome 5A with an supernumary chromosome 5B in
      offspring of a somaclonal common wheat line monosomic for 5A].
AB  - Cytogenetic analysis was employed in studying the cause of generation of fertile
      awned forms in the progeny of plants, which were selected from a speltoid
      somaclonal wheat line monosomic for chromosome 5A (2n = 41 = 20II + I), had
      speltoid spikes, and were reproduced by self pollination. On cytogenetic and
      genetic evidence, chromosome 5A was eliminated and the copy number of chromosome
      5B increased in the plants examined. The appearance of an extra chromosome 5B is
      probably caused by nondisjunction of bivalent 5B in the presence of a telocentric
      originating from the long arm of chromosome 5A. A difference in meiotic
      segregation was observed for univalent chromosomes 5A and 5B.

PMID- 14964834
TI  - [Analysis of specific RAPD- and ISSR-fragments in somaclonal maize (Zea mays L.)
      and development of SCAR markers based on them].
AB  - RAPD (Random Amplified Polymorphic DNA) and ISSR (Inter Simple Sequence Repeats)
      markers were used to analyse the genetic divergence between the regenerated
      plants derived from callus cultures and the original maize line A188. Analysis of
      polymorphism by using 38 RAPD- and 10 ISSR-oligonucleotide primers showed that
      the differences between eight examined somaclones and the original line ranged
      from 6.5 to 23%. As confirmed using new primers, the regenerants derived from
      callus cultures grouped into two clusters according to their origin. The
      regenerants isolated from calluses grown for eight months differed from one
      another and the original line to a larger extent than the regenerants obtained
      from two-month callus cultures. In some somaclones, molecular marking of the
      regenerants revealed specific RAPD and ISSR fragments that were absent in other
      somaclones or the original maize line. On the basis of six specific fragments
      (five RAPD and one ISSR), SCAR (Sequence Characterized Amplified Region) markers
      were developed. Specific polymorphism revealed with random primers was completely
      confirmed using five SCAR markers. Polymorphism of one SCAR marker differed from
      that revealed with random primers. Five SCAR fragments were inherited as simple
      dominant traits. One SCAR fragment displayed codominant inheritance.

PMID- 14964835
TI  - [Features of recombination of nuclear genome in back crossed offspring of barley
      wheat hybrids Hordeum vulgare L. (2n=14) x Triticum aestivum L. (2n+42) with the
      use of SSR-analysis].
AB  - The backcross progenies of the barley-wheat hybrids Hordeum vulgare L. (2n = 14)
      x Triticum aestivum L. (2n = 42) and two alloplasmic lines derived from them were
      studied using microsatellite markers of barley and wheat. The F1 hybrids and
      first backcross plants BC1 contained the genetic material of both cultivated
      barley and the cultivars of common wheat involved in developing of these hybrid
      genotypes. The genomes of BC3, BC4, and alloplasmic lines contained no
      microsatellite markers of the cultivated barley, whereas chromosomes of each
      homeologous group of common wheat were identified. In chromosomes of backcross
      progenies BC3, BC4, and alloplasmic lines yielded by backcrosses of hybrids and
      various common wheat cultivars, microsatellite markers of the parental wheat
      cultivars were shown to undergo recombination.

PMID- 14964836
TI  - [On the question of using alleles of gliadin-coding loci as possible markers of
      adaptive ability in cultivars of spring wheat (Triticum aestivum L.) during seed
      germination].
AB  - Prolamine proteolysis is assumed to be among numerous adaptability factors in
      cereals. The patterns of gliadin proteolysis have been studied in 16 cultivars of
      spring wheat via analysis of electrophoretic spectra. Four proteolytic patterns
      have been identified. It is hypothesized that the cultivars characterized by
      early and rapid proteolysis (the first and third types) are the most adaptable.
      The gliadin genetic formulas of chromosomes of the first homeologous group have
      been determined. The alleles of gliadin loci (Gli-Alf, Gli-Ble, Gli-D1a, and Gli
      D1b) have been found that can be used as markers of adaptability in spring wheat
      cultivars.

PMID- 14964837
TI  - [Divergence of mitochondrial DNA in a population of sockeye salmon (Oncorhynchus
      nerka Walbaum) from Azabache'e lake (Kamchatka)].
AB  - Variability of three PCR-amplified mtDNA regions was examined in five populations
      of sockeye salmon from Azabach'e Lake. Eighteen haplotypes were detected in 144
      fish. Significant differences were found between seasonal races of sockeye salmon
      spawning in the lake. The short time of independent divergence between the
      seasonal races indicates that these races formed independently in each spawning
      region. No difference in mtDNA between lake samples of early sockeye salmon
      (subisolates) was revealed, which confirms the existence of gene flow between
      them. A high level of differences between the sockeye salmon spawning in the lake
      and spawning in the tributaries of the lake, the Bushuev and Lotnaya rivers,
      suggests that there were no migration between them during many generations and
      that the nature of spawning grounds (lake or river) is essential for within
      species differentiation in this species.

PMID- 14964838
TI  - [Signs of fitness and allozyme heterozygosity in an artificial population of
      sable Martez zibellinna L].
AB  - Associations between some characteristics of fitness (the age of the first
      reproduction, life span, fertility, and number of missed pregnancies) and
      heterozygosity for some allozyme loci have been studied in a population of the
      sable Martez zibellinna L. kept in cages at a farm. Of all fitness characteristic
      studied, a weak correlation has only been found between heterozygosity and the
      age of the first reproduction (maturation rate). The age of the first
      reproduction is positively associated with the life span and fertility. The
      results obtained are discussed in terms of the relationship between the genetic
      variation of longevity and developmental rate and prospects of their application
      to breeding practice.

PMID- 14964839
TI  - [Analysis of marital migrations in two regions in the Sakh republic (Iakutiia)].
AB  - The marital migration structure of two ouluses (administrative districts) of the
      Republic of Sakha (Yakutia) that have long been populated by three ethnic groups
      were studied on the basis of marriage records. Population genetic characteristics
      were calculated for each ethnic group. The ethnic assortativeness values were
      30.9 in Evens, 1.36 and 4.46 in Russians, and 1.03 and 4.51 in Yakuts. The
      endogamy indices for the oulus and republican ethnic populations, respectively,
      were 0.83 and 1.0 in Evens, 0.41 and 0.99 in Yakuts, and 0.08 and 0.14 in
      Russians. The parameters of isolation by distance were the following: a = 0.0013
      and b = 0.0020 in the Gornyi oulus; a = 0.0048 and b = 0.0014 in the Krest
      Khaldzhai rural municipality; a = 0.0086 and b = 0.0095 in the Topolinoe rural
      municipality; and a = 0.0106 and b = 0.0013 in the Megino-Aldan rural
      municipality.

PMID- 14964840
TI  - [Correlation between family and age of manifestation of lung and colon cancer].
AB  - The probability to develop lung cancer before 80 years of age is 1.67 and 0.18%
      for the male and female populations of Kharkov, respectively; the probability to
      develop large-intestine cancer is 0.92 and 0.49%, respectively. The correlation
      coefficient (r) of the age of manifestation (AM) of cancer in parent-offspring
      pairs is 0.47. These correlation coefficients for the father-son, mother
      daughter, mother-son, and father-daughter pairs are 0.64, 0.49, 0.44, and 0.37,
      respectively. If the parent has lung cancer, the correlation is stronger (r =
      0.71). On average, cancer is manifested in offspring earlier than in parents (57
      and 63 years, respectively); the differences in the father-daughter and mother
      son pairs are 8.2 and 2.8 years, respectively. The best prognostic parameter is
      the AM of cancer in the father with respect to the AM in the son (byx = 0.45).

PMID- 14964841
TI  - [Genetic history of Aleuts of the Komandor islands from results of analyzing
      variability of class II HLA genes].
AB  - Variability of the HLA class II genes (alleles of the DRB1, DQA1, and DQB1 loci)
      was investigated in a sample of Aleuts of the Commanders (n = 31), whose
      ancestors inhabited the Commander Islands for many thousand years. Among 19
      haplotypes revealed in Aleuts of the Commanders, at most eight were inherited
      from the native inhabitants of the Commander Islands. Five of these haplotypes
      (DRB1*0401-DQA1*0301-DQB1*0301, DRB1*1401-DQA1*0101-DQB1*0503, DRB1*0802
      DQA1*0401-DQB1*0402, DRB1*1101-DQA1*0501-DQB1*0301, and DRB1*1201-DQA1*0501
      DQB1*0301) were typical of Beringian Mongoloids, i.e., Coastal Chukchi and
      Koryaks, as well as Siberian and Alaskan Eskimos. Genetic contribution of the
      immigrants to the genetic pool of proper Aleuts constituted about 52%.
      Phylogenetic analysis based on Transberingian distribution of the DRB1 allele
      frequencies favored the hypothesis on the common origin of Paleo-Aleuts, Paleo
      Eskimos, and the Indians from the northwestern North America, whose direct
      ancestors survived in Beringian/southwestern Alaskan coastal refugia during the
      late Ice Age.

PMID- 14964842
TI  - [Burden of hereditary diseases in residents of the Sakh republic (Iakutiia)].
AB  - Summarized data of medical genetic survey of the population of Republic of Sakha
      (Yakutia) are presented. The number of the population examined constituted
      1000700 individuals (including 424500000 of urban and 576,200 of rural
      population, respectively). Regarding the ethnicity, 33 regions of the Republic
      examined were at most inhabited by Yakuts (36%) and Russians (55%). A total of
      400 families (606 patients) with autosomal dominant, 274 families (369 patients)
      with autosomal recessive, and 42 families (53 patients) with X-linked pathologies
      were detected. The segregation analysis performed showed good correlation with
      the expected type of inheritance for both dominant and recessive diseases. The
      prevalence rate of monogenic hereditary diseases for rural and urban populations,
      as well as for solely Yakuts, was calculated. It was shown that weighted average
      prevalence of dominant (0.68; 1.44) and recessive (0.43; 0.86) disorders in
      Yakuts was two times higher than in total population examined.

PMID- 14964843
TI  - [Cultivar identification of monosomal series of common wheat].
AB  - Storage proteins (gliadins) were employed in cultivar identification of a
      monosomic series obtained on the basis of a Swedish accession. The cultivar was
      identified as Diamant 2.

PMID- 14964844
TI  - [Structure and seasonal dynamics of an ectoparasite community on the common shrew
      (Sorex araneus) in the Il'men'-Volkhov lowland].
AB  - Species composition, seasonal dynamics, and a load of ectoparasites per
      individual and population of the common shrew Sorex araneus have been examined in
      coniferous and mixed forests of the Ilmen'-Volkhov lowland (a neighbourhood of
      Oskuy village, Chudovo district, Novgorod Province) during the period 1999-2003.
      Trapping of mammals was carried monthly, with exception of few accidental gaps.
      The Gero traps were used for catching micromammalian hosts. The lines of trap
      were checked 2 times a day, places of lines changed each 3-5 day. Total number of
      micromammalians collected during the period of study is 3215, including 1115
      specimens of the common shrew S. araneus and 246 ones of the pigmy shrew S.
      minutus. Parasite fauna on the common shrew included 23 ectoparasite species:
      fleas--12, ixodid ticks--2, gamasid mites--7, and myobiid mites--2 species. Among
      recorded species, 9 fleas species and some gamasid species are accidental
      parasites. These accidental ectoparasite species are common to the bank vole
      Clethrionomys glareolus in the territory investigated. Species composition,
      occurrence and abundance indices of parasites changed during the year. In total,
      about 55% shrew specimens are infected with ectoparasites. The infracommunity of
      ectoparasites on the common shrew usually consists of 6 species or less. Mean
      number of all ectoparasite individuals per one host specimens varies from 4 to
      83. The greatest number of parasites (50 and 83) was recorded on the shrews,
      which carried 5 and 4 parasites species, respectively. Biodiversity of parasite
      species in the ectoparasite community on the common shrew and the load of
      parasites per one host specimen are lower than those in the bank vole. In forest
      biotopes explored, the most part of temporary ectoparasite species found on the
      common shrew was also recorded on other small mammals, which could have contacts
      with this host. It is possible to conclude that among the parasite supracommunity
      in the explored ecosystem, the temporary ectoparasites represent a "fond" of
      temporary parasites, which are common for most small mammal species. A role of
      different shrew and rodent species as main of additional hosts changes depending
      on a population density of potential mammalian hosts and other environment
      factors.

PMID- 14964845
TI  - [Prototypes of Hyalomma scupense Schulze, 1918 and H. detritum Schulze, 1919
      (Acari: Ixodidae) in connection with microevolution within the genus].
AB  - Type series of two species of the genus Hyalomma Koch, 1844 deposited in the
      Museum of Zoology in Berlin have been examined. Examination of the H. detritum
      Schulze, 1919 holotype has shown that this name is actually a junior synonym
      (syn. nov.) of H. marginatum turanicum Pomerantsev, 1946. At the same time it was
      also found out that the paratypes of H. detritum are conspecific to the syntypes
      of H. scupense Schulze, 1818, among which the lectotype has been designated.
      Taxonomic errors of Schulze and other authors, which had led to a worldwide use
      in acorological literature the name H. detritum instead of the valid name H.
      scupense, are discussed. It is suggested that the reasons of microevolution
      within the polymorphic species H. scupense could be explained by unequal climatic
      conditions. Microevolutionary process in this species is most well expressed in a
      tendency to reduce the number of contacts with a host during the life cycle. It
      has resulted in the reformation of the two-host cycle into the one-host cycle.

PMID- 14964846
TI  - [Differentiation of subspecies of the polymorphic species Hyalomma marginatum
      (Acari: Ixodidae) based on immature stages].
AB  - Study of morphological characters to identify the subspecies of Hyalomma
      marginatum immature stages is based on material collected throughout all the
      geographical range of the species. As it was found, the discrimination of
      subspecies of H. marginatum immature stages needs a complex use of structural and
      morphometrical characters. Only H. m. marginatum larvae and H. m. isaaci nymphs
      may be easily differentiated from other subspecies based on the structural
      (qualitative) characters. Besides, morphometric (quantitative) characters should
      be used only in combinations for identification of the subspecies. In regard to
      structural characters of larvae, it was found that the shape and size of coxal
      spurs of H. marginatum allow differentiating this subspecies from the others
      (Fig. 3, 5, 6). Based on morphometrical characters of larvae, the following
      characteristic features of subspecies have been found: in H. m. marginatum, the
      capitulum is wide, the palpi, hypostome and genua I are short and narrow; in H.
      m. turanicum, the capitulum is narrow, the palpi are short and narrow, the
      hypostome is short and wide, the genua I are long and narrow; in H. m. rufipes,
      the scutum is large, the capitulum is wide, the palpi are long and narrow, the
      hypostome and genua I are long and wide; in H. m. isaaci, the scutum is small,
      the capitulum is narrow, the palpi and hypostome are long and narrow, the genua I
      are short and narrow. Among structural characters of nymph, several
      discriminative features of subspecies have been found. The shape of the scutum in
      H. m. isaaci (Fig. 2, 2) clearly differentiates this subspecies from the others
      (Fig. 2, 1). In H. m. marginatum, the setae of alloscutum as a rule have bluntly
      rounded apices (Fig. 1, 2), while in the other subspecies these setae are more
      tapering apically (Fig. 1, 1). The shape of spiracular plates is rather variable
      within the species, but in H. m. marginatum and H. m. isaaci (Fig. 1, 3) the
      plates are larger and more perforated than in H. m. rufipes and H. m. turanicum
      (Fig. 1, 4). In H. m. isaaci, the spurs of coxae I are narrower than in other
      subspecies (Fig. 1, 8). Based on morphometrical characters of nymphs, the
      following discriminative features of subspecies have been found: in H. m.
      marginatum, the capitulum is wide, the palpi are short and wide; in H. m.
      turanicum, the capitulum is narrow, the palpi are long and narrow; in H. m.
      rufipes, the scutum is wide, the capitulum is narrow, the palpi are long and
      narrow, the hypostome is long; in H. m. isaaci, the scutum is long and narrow,
      the capitulum is wide, the palpi are short and wide, the hypostome is short.

PMID- 14964847
TI  - [Fleas (Siphonaptera) infesting birds of West Siberian plain].
AB  - The four species of fleas associated with birds in West Siberian Plain have been
      recorded. Ceratophyllus styx is a specific parasite of Riparia riparia.
      Ceratophyllus garei, C. gallinae, and C. tribulis parasitize various setting of
      birds.

PMID- 14964848
TI  - [Biotope distribution of cestodes from the common shrew Sorex araneus in southern
      Karelia].
AB  - Specific features in the formation of cestode species composition in the common
      shrew in different biotopes have been analyzed. Four categories of parasites have
      been recognized depending on a degree of dominance: dominants (Neoskrjabinolepis
      singularis, Molluscotaenia crassiscolex), subdominants (Ditestolepis diaphana),
      adominants A (Staphylocystis furcata, Vigisolepis spinulosa, adominants B
      (Hymenolepis scutigera, Dilepis undula, D. secunda, Taenia mustelae). A
      significant similarity was discovered between the species diversity and the
      dominance characteristics of cestodes. It was found that the distribution of mass
      species of parasites in the host population corresponds to the gamma distribution
      model. In regard to cestodes examined, a hypothesis considering the spatial
      structure and size of territory occupied by stable parasitic system is put
      forward.

PMID- 14964849
TI  - [A new cestode species Paranoplocephala gubanovi sp.n. (Cyclophyllidea:
      Anoplocephalidae) from the wood lemming Myopus schisticolor of eastern Siberia].
AB  - A new species of anoplocephalid cestode, Paranoplocephala gubanovi sp. n.
      (Cyclophyllidea, Anoplocephalidae), from wood lemmings of Eastern Siberia (Myopus
      schisticolor) is described. The new species differs from other known species of
      Paranoplocephala associated with Holarctic lemmings by having unique combination
      of characters as follows: a few-segmented strobila, superficial suckers sticking
      out of the scolex, ovary covering practically the whole middle part of the
      segment, relatively little number of testicles situated in the aporal part of the
      segment, cirrus bursa crossing the poral excretory vessels, and subspherical
      spermatheca situated in the middle part of the segment. Comparison of P. gubanovi
      sp. n. and several closest species, P. fellmani Haukisaimi et Henttonen, 2001, P.
      serrata Haukisaimi et Henttonen, 2000, and P. arctica (Rausch, 1952) has been
      carried out. Features distinguishing the new species from Aprostatandrya
      macrocephala and A. microti have also been studied.

PMID- 14964850
TI  - [Final stages of carbohydrate metabolism in a cestode Eubothrium rugosum
      (Cestoda: Pseudophyllidea)].
AB  - Characteristics of final stages of carbohydrate metabolism in a cestode
      Eubothrium rugosum from the burbot intestine have been studied. It is found out
      that in the course of in vitro incubation the worms produce lactic acid to the
      environment with a concomitant acidification of the medium. The rate of pH
      changes and lactate production eventually fell during the incubation. The medium
      pH being the result of helminth's metabolism varies within the normal
      physiological limits of the host intestine pH and pH optima for its basic
      digestive enzymes.

PMID- 14964851
TI  - [A comparative biochemical research in the Schistocephalus solidus (Cestoda)-
      three-spined stickleback Gasterosteus aculeatus L. system].
AB  - The activity of five lysosomal hydrolases (acid phosphatase, DNAase, RNAase, beta
      glucosidase, beta-galactosidase), alkaline phosphatase and aldolase have been
      examined in tissues of the cestode Schistocephalus solidus (Muller, 1776) and the
      three-spined stickleback Gasterosteus aculeatus (L.) forming a stable parasite
      host system. As a rule, the activity of enzymes was higher in a cestode body than
      in fish tissues. The acid and alkaline phosphatases were the exception. The
      activity and variation of lysosomal nucleases and aldolase in the parasite
      differed notably from those in both infested and healthy hosts. The paper
      discusses the role of lysosomal and cytoplasmic enzymes in a cestode adaptation
      to parasitism, as well as in the mechanisms of the host's chemical and
      immunological response to infection.

PMID- 14964852
TI  - [Two new nematode species found in amphibians and reptiles from the north part of
      Fergana valley].
AB  - Two new species of nematodes found, in the north of Fergana Plain (Uzbekistan):
      Raillietnema uzbekistanica sp. n. (Cosmocercidae) from the Horsfields Tortoise
      Testudo horstfieldi (Testudinidae), and Spironoura govacus sp. n. (Kathlaniidae)
      from the green toad Bufo viridis (Bufonidae). Data on infection of R.
      uzbekistanica sp. n. with predatory fungi in different seasons are given.

PMID- 14964853
TI  - [Distribution of coccidians (Coccidea) among different groups of hosts].
AB  - Approximately 3660 species of Coccidea belonging to 73 genera and 29 families
      parasitize representatives of the Metazoa kingdom. Coccidea were discovered in 10
      of 35 phyla of Metazoa; in the most cases a direct correlation between the number
      of species in a host group and the number of Coccidea known from that group is
      clearly traced. Host groups, which are most archaic phylogenetically, are also
      parasitized by the archaic Coccidea groups. Evolutionarily derived hosts are
      parasitized by groups of Coccidea, which are the youngest phylogenetically.
      Parallel development of Coccidea and their hosts may be used for an indirect
      determination the time of origin of different Coccidea groups.

PMID- 14964854
TI  - [Longevity of forest and taiga ticks (Ixodidae) infected and non-infected with
      Borrelia burgdorferi groups].
AB  - A life longevity of Ixodes ricinus and I. persulcatus have been examined in
      laboratory conditions. It was found that specimens infected with borreliae live
      slightly longer than non-infected ones (difference is not reliable); females live
      1.5 times longer than males; I. ricinus lives 2-4 times longer than I.
      persulcatus. It is suggested that I. persulcatus has a higher rate of metabolism
      than I. ricinus and that the latter species obtains an ability to survive after
      the last moult two winters and keep an activity in two summer seasons not
      counting the year of moulting.

PMID- 14964855
TI  - [Dactylogyrids from the Siberian loach Nemachilus barbatulus toni in Primor'e
      region].
AB  - Two species of dactylogyrids, Dactylogyrus barbatuli Ermolenko, 1992 and D. tonii
      Ermolenko, 1992, occurring in the Siberian stone-loah in Primorye are
      redescribed. These species are distinguished from others monogenean of the genus
      Dactylogyrus, that are found in fishes of the genus Nemachilus, by the size of
      anchor structures and complexes of copulatory organs.

PMID- 14964856
TI  - [Thirty years of the electron microscope investigation in zoology and
      parasitology in the Zoological Institute of the Russian Academy of Sciences].
AB  - The history of the electron microscope investigations in zoology and parasitology
      in the Zoological Institute of the Russian Academy of Sciences and progress in
      scanning and transmission electron microscope investigations in this field of
      biology to the moment are briefly accounted.

PMID- 14964857
TI  - [Express control of toxic substances and pathogenic microorganisms. Immune
      analysis and immune sensors].
AB  - In the review the overall characteristics of biological warfare components, which
      represent danger to people in the case of their application by military or
      terrorist groups are discussed. The main part of the review is devoted to modern
      approaches of antibody obtaining and, in particular, preparation of specific
      recombinant immunoglobulins as well as to different immune chemical methods of
      determination of individual toxins and pathogenic microorganisms. A special
      attention is paid to existing data about the development of rapid, selective,
      high sensitive, simple and fully automated instrumental methods on the basis of
      biosensor technology which is designed for the control of components of
      biological warfare in environmental objects. Additionally industrially
      manufactured biosensors and their characteristics are given and analyzed.

PMID- 14964858
TI  - [Functioning of fructose-1,6-bisphosphatase--main enzyme of gluconeogenesis in
      microorganisms].
AB  - The modern literature data about common characteristics, genetic and molecular
      biological properties of main enzyme of gluconeogenesis (fructose-1,6
      bisphosphatase) were analyzed. Regulation of fructose-1,6-bisphosphatase activity
      (stimulation and inhibition) by fructose-1,6-bisphosphate, fructose-2,6
      bisphosphate, phosphoenolpyruvate, AMP and by metal ions are discussed. It was
      concluded that apart from the fact that fructose-1,6-bisphosphatase was
      intensively investigated, this enzyme from Mollicutes failed to be studied
      sufficiently.

PMID- 14964859
TI  - [New forms of gene transcripts in human and mouse intersectin].
AB  - New human and mouse cDNAs which are homologous to human intersectin gene (ITSN)
      mapped on a q22.1-22.2 region of human chromosome 21 have been obtained. ITSN
      gene structure has been determined using nucleotide sequences of human chromosome
      21 presented in nucleotide's data bases. The analysis of human and mouse ITSN
      gene transcripts revealed that their pre-mRNA splicing could occur in different
      ways. New form of ITSN gene transcripts with alternatively spliced SH3C domain
      (exon 25 and 26) was detected in different human and mouse tissues. The other
      splice form with absence of exons 6-14 that results in reading frame shift and
      stop-codon formation was identified in the mouse adult lung and kidney. In
      addition, we showed alternative splicing of exons 20, 25 and part of exon 6.

PMID- 14964860
TI  - [Effect of phospholipids containing omega-3 fatty acids on structural changes of
      microsomal lipids in cell membranes of functionally different cells].
AB  - As a result of the experimental researches conducted it has been shown that
      administration of some normal animal marine phospholipids (PL) including in their
      structure omega-3 polyunsaturated fatty acids (PUFA) provides for quantitative
      changes of individual PL, fatty acids (FA) content and quantity in general and
      individual PL of liver, heart, brain and gonads microsomes. While estimating
      general microsomal PL fraction FA content under the action of PL omega-3 PUFA FA
      concentration change, unsaturation index (omega 6/omega 3) and relation of
      arachidonic acid to docosahexenic (AA/DHA) decrease have been identified. The
      decrease of AA/DHA relationship occurs due to AA and DHA quantitative changes. In
      the case of AA increase in some tissues there is observed the decrease of
      docosapentaenic acid and increase of DHA and eucosapentaenic (EPA) acidds. As a
      result of studying FA content in the individual PL composition it has been
      identified that certain PL classes characteristic for some tissues respond by
      changes of some certain FA. The relationship omega 6/omega 3 has been shown as
      decreasing in phosphatidilcholine (PC) all tissues microsomes (liver, gonads,
      heart, brain), in phosphatidilethanolamine (PEA) of liver and cardiac microsomes,
      in phosphatidilserine (PS) this relationship relationship decreases in the liver,
      brain and heart, for phosphatidilinositole (PI) the changes take place in liver,
      gonads, brain. Simultaneously, the decrease of AA/DHA relationship in the
      individual PL decrease of AA and increase of EPA and DHA depend on the tested
      tissues. The marine phospholipids might be supposed to render their effect on AA
      metabolism resulting in AA/DHA relationship in PEA and PS relationship displays
      itself as specific and depends on the tissues functions. The preference of PEA
      and PS use by certain tissues microsomes could be explained by their membrane
      protective capability.

PMID- 14964861
TI  - [State of biological membranes in rats tissues with different audiogenic
      susceptibility].
AB  - The decrease of sphingomyelin in synaptosomes of brain hepatocytes, erythrocytes
      and the increase of lysophosphatidylcholine in hepatocytes and erythrocytes were
      found in rats with high seizure susceptibility. Activities of
      acetylcholinesterase and Mg(2+)- and Ca(2+)-ATPase were not changed. Permeability
      of erythrocyte membranes to K+ increased. The importance of obtained changes in
      phospholipid composition of membranes for their structural and functional state
      is discussed.

PMID- 14964862
TI  - Production of antibodies to alpha(181-192) peptides of neuronal nicotinic
      acetylcholine receptor coupled to protein carriers in different orientations.
AB  - The antibodies to nicotinic acetylcholine receptor alpha(181-192) synthetic
      peptides were elicited in rabbits and mice using the peptides conjugated to
      protein carriers in different orientations, either through C-terminal Cys (S
      conjugates), or through amino groups (N-conjugates). S-conjugated peptides were
      less potent in eliciting peptide-specific antibodies compared to N-conjugates and
      this type of conjugation resulted in antibodies to the coupling reagent. However,
      the epitopes present in either S- or N-conjugated peptides appeared to be
      similar, indicating that amino acid residues, which form the epitope, were
      located in the middle part of the peptide and did not include both N- and C
      terminal residues. Peptide conjugation to a protein carrier did not play a role
      in stabilizing the peptide conformation, but was necessary to concentrate the
      peptide epitopes on the carrier surface enabling bivalent antibody binding.

PMID- 14964863
TI  - [Modifying effect of antiplasminogen monoclonal antibody IV-1c on human plasmin
      catalytic properties].
AB  - Antiplasminogen monoclonal antibody IV-1c (IV-1c) binds to Val 709-Gly 718 site
      of plasminogen (Pg) protease domain, which is far removed from the active site.
      Pg-IV-1c complex formation induces catalytic activity in proenzymes active site.
      Influence of IV-1c binding to plasmin (Pm) on Pm catalytic properties has not
      been investigated yet. Data on catalytic properties of Pm in equimolar Pm-IV-1c
      complex are presented. It was found that Pm and mini-Pm amidolytic and
      caseinolytic activity was twice as high as in Pm-IV-1c and mini-Pm-IV-1c
      complexes. 20 mM 6-AHA and 100 mM arginine did not influence this rise. The
      increase of amidolytic activity is connected with reduction of K(m) of S 2251
      hydrolysis reaction for Pm and mini-Pm from 0.125 and 0.43 to 0.05 and 0.23 mM,
      correspondingly. Kcat remains almost the same. Fibrinolytic and fibrinogenolytic
      activity of Pm in Pm-IV-1c complex decreased to 20% of initial value alpha 2
      Antiplasmin inhibited Pm activity in complex Pm-IV-1c by 80%. Pm-IV-1c complex
      did not activate free Pg, but activated equimolar Pg-IV-1c complex. Affinity of
      IV-1c to Pm and Pg was the same as C50 approximately 1.5 nM. Binding of Pm with
      IV-1c in a complex: a) leads to increase of Pm active site affinity to LMW
      substrates; b) causes steric hindrances for fibrin/fibrinogen access to Pm active
      site; c) proceeds with the same affinity for Pm and Pg, that indicates to
      invariable Val 709-Gly 718 site conformation after Pg transition in Pm.

PMID- 14964864
TI  - [Orientation of proteins on the sensor surface and optimization of their
      immobilization by prior protection of the active center].
AB  - When studying biospecific interactions with application of surface plasmon
      resonance, one of the main problems is reagent proper orientation to the sensor
      surface. Due to rather high chemical activity of molecular receptor sites, the
      interaction between these areas and surface may become predominant. Here we
      propose a technique for prevention of such orientation of bioreceptors using
      soybean trypsin inhibitor STI as an example. To obtain oriented STI
      immobilization on a modified gold surface its active site has been previously
      blocked through interaction with its specific partner trypsin. After conjugate
      immobilization on the sensor surface the components were separated using a
      glycine buffer (pH 2.2).

PMID- 14964865
TI  - [Activity of NO-synthase, apoptosis signal-regulating protein kinase 1, poly-(ADP
      ribose)-polymerase, protein kinase C, serine proteinases and DNA fragmentation in
      rat liver during molybdenum-dependent induction of xanthine oxidase ].
AB  - It was discovered that nitric oxide synthase activity and concentration of S
      nitrosothiols decreased during molybden-dependent xanthine oxidase activation.
      The increase of apoptosis signal-regulating kinase 1 activity, with the respected
      decrease of [table: see text] poly-(ADP-ribose)-polymerase and protein kinase C
      activities as well as increase of trypsine like serine proteinases activity were
      observed. No significant changes of DNA fragmentation were revealed.

PMID- 14964866
TI  - [Protein synthesizing cell apparatus in malignant growth and pharmacotherapy by
      chlofiden].
AB  - Data on the influence of a new antitumor preparation chlofiden on the general
      contents of rat liver ribosomes and sarcoma 45 and their division on free and
      membrane of membrane bound and decrease of free ribosomes during tumor growth
      supposed synthesis of specific proteins bound are given in the paper. It was
      shown that in the liver of tumor bearing rats total and membrane bound ribosomes
      decreased and the level of free ribosomes increased. High contents of free
      ribosomes in sarcoma 45 may testify increase of intracellular protein synthesis
      including processes of cell growth and division as well as the tendency for
      increase. Chlofiden normalized total contents, increased free and decreased liver
      membrane bound ribosomes contents, during tumor growth supposed synthesis of
      specific proteins. Increase of free ribosomes and decrease of their specific
      radioactivity in sarcoma 45 testified membrane damage by chlofiden and inhibition
      of intracellular protein synthesis which are essential in cell division.

PMID- 14964867
TI  - [Effect of tricarboxylic acid cycle intermediates on nitric oxide system during
      acute hypoxia].
AB  - Effects Crebs Cycle of exogenous intermediates sodium succinate (50 mg/kg) and
      sodium alpha-ketoglutarate (200 mg/kg) on processes of mitochondrial ADP
      stimulated respiration (using as substrates of oxidation 0.35 mM succinate, 1 mM
      alpha-ketoglutarate), production of nitric oxide under NO2-, NO3-, as well as
      carbamide, putrescyne content and processes of lipid peroxidation in the rats
      liver under acute hypoxia (7% O2 in N2, 30 min) have been studied. It was shown,
      that the exogenous sodium alpha-ketoglutarate increases nitric oxide content,
      aminotransferase activation, inhibition of succinatedehydrogenase simultaneously
      more than exogenous sodium succinate. It correlates with decreasing of processes
      lipid peroxidation in liver.

PMID- 14964868
TI  - [Liquid photo-polymerized compositions as an immobilized matrix of biosensors].
AB  - Series of liquid photopolimerized compositions based on oligourethanemetacrylate
      (OUM-1000T and OUM-2000T) and oligocarbonatemethacrylate (OCM-2),
      butilmethacrylate, methacrylic that acid, monomethacrylic ether of ethylene
      glycol and vinylpirrolidone (VP) were tested. It was shown the optimal variant of
      enzyme sensor development was a composition containing VP (a basic hydrophylic
      matrix), OCM-2 (crosslinked components) and OUM-2000T (crosslinked and increasing
      adsorption of polymer component). The blend contains 3% of enzyme. The obtained
      biosensors as based on immobilized beta-glucose oxidase and ureases have the
      following charachteristics: the linear response in the range of the concentration
      0.1-10 mM, 0.05-20 mM, angle of slope of curve 30 mV/pC, 38 mV/pC, and response
      time 10-15, 5-10 mines, respectively. The maximal response of urease sensor was
      in the diapazon of pH 6.0-6.5. The increase of NaCl concentration in the solution
      to 300 mM caused reduction of sensor response. Under this concentration the was
      latter equal to half of initial response. Further increase of NaCl concentration
      (to 500 mM) doesn't lead to further response reduction. K(m) was calculated and
      it was shown, that amount of immobilized urease and beta-glucose oxidase in
      photopolymer material was equal 0.85 and 3.1 mM respectively.

PMID- 14964869
TI  - [Application of lectins for determination of antibodies to glycoproteins of
      leukemia virus in bovine blood serum].
AB  - The possibility of using different lectins for the determination of level of
      specific antibodies to leukosis virus virus in bovine blood serum whit the help
      of the surface plasmon resonance was investigated. The modification of transducer
      surface with lectins provides for immobilisation of glycosilated proteins of
      leukaemia virus. It allows to make selective determination of antibodies to
      glicosilated protein, the quantity of which more high in blood serum of ill
      animals in the comparison with the immunised ones. Moreover, the treatment of
      surface with FGA-P and PLA lectins increases the sensitivity of immune sensor to
      the specific antibodies in the comparison with the non-treated one.

PMID- 14964870
TI  - [Effect of mercury chloride on the level of lipids and products of their
      peroxidation in rat vital organs].
AB  - The influence of mercury chloride on peroxidation processes of lipids and level
      of common lipids, phospholipids and spectrum of neutral lipids in liver, heart,
      lung and kidney of rats has been investigated. Administration of mercury chloride
      in a dose 0.7 mg/100 g of body weight to animals has invoked accumulation of
      lipids peroxide products in fractions of neutral lipids and phospholipids so it
      testifies the development of oxidative stress. Decrease of the most sensitive to
      oxidation fractions in the early stages of oxidative stress development and
      increase of free cholesterol and its ethers content in kidney and free
      cholesterol in the heart in more later terms as a result of mercury chloride
      administration have been revealed.

PMID- 14964871
TI  - [Comparative characteristics of physico-chemical and regulating properties of
      aspartate kinases from three species of cyanobacteria].
AB  - Aspartokinases have been isolated from the cell-free extracts of Plectonema
      boryanum, Anabaena variabilis and Synechococcus cedrorum. Their physico-chemical
      characteristics and peculiarities of retroregulation by amino acids were studied.
      It has been shown that in P. boryanum cells aspartokinase reaction is catalyzed
      by only one enzyme, which is similar to the previously described bacterial origin
      enzymes. Three izoenzymes, which differ in their main properties and amino acids
      effectors, have been founded in the cells of A. variabilis. One enzyme with
      aspartokinase activity, which differs from other cyanobacteria enzymes in some
      physico-chemical features has been founded in the cells of S. cedrorum.

PMID- 14964872
TI  - [Level of nitric oxide in the kidneys during apoptosis activation].
AB  - The content of nitric oxide stable metabolites in a tissue of kidneys of rats in
      conditions of activation of apoptosis was investigated. Research was carried out
      in two models: acute renal failure and a hypertrophy of a unique kidney after a
      unilateral nephrectomy. Detection of apoptosis was carried out by definition of
      DNA fragmentation. Substantial increase of the nitric oxide stable metabolites
      contents is revealed at activation of apoptosis in both models. Change of a ratio
      of the contents of nitrite--anions in relation to the general contents of NO2- +
      NO3- is revealed, indicating the role of peroxide processes in effect of nitric
      oxide and its metabolites on the cell.

PMID- 14964873
TI  - [Formation of antioxidant defence system of geese in embryogenesis and early
      postnatal ontogenesis].
AB  - The features of antioxidant protection of tissues of a liver and blood of the
      gooses in embriogenesis and early postnatal ontogenesis are found out. Maximal
      contents TBA active products both in a liver, and in a blood are observed in 28
      diurnal embriones. Is shown, that in a liver the activity of basic antioxidant
      enzymes (superoxide dismutases, catalase and glutathione peroxidase) in a liver
      is developed already at early stages embriogenesis and is considerably enlarged
      in the end embriogenesis. The becoming of enzymatic system of a blood descends
      much more slower.

PMID- 14964874
TI  - [Effect of beta-carotene accumulation on spectral parameters of microscopic fungi
      Blakeslea trispora biomass].
AB  - Parameters of reflectance spectra in visible region and colorimetry for Blakeslea
      trispora biomass with different content of beta-carotene were determined.
      Correlation level of pigment accumulation and spectral characteristics were
      revealed. It is established, that objective control of color characteristics for
      biomass is possible using measurement of colorimetric parameters.

PMID- 14964875
TI  - [Method of detection of protein kinase activity in polyacrylamide gel using two
      dimensional protein separating system].
AB  - Method for detection of protein kinase activity in polyacrylamide gel have been
      developed. After separation of proteins by isoelectric focusing in non-denaturing
      condition, gel was incubated in a reaction buffer containing [gamma-32P]ATP. 32P
      labeled proteins were separated by subsequent SDS/PAGE electrophoresis in second
      dimension. The proposed method was used for detection of protein kinase activity
      in human blood serum and triton X-100 soluble proteins of heads of Drosophila
      melanogaster.

PMID- 14964876
TI  - [Method of isolating isoflavone aglycones from soya beans].
AB  - The method of isolating isoflavone aglycones from soya beans has been proposed.
      The procedure includes the extraction by hot water, glycosides oxidative
      hydrolysis, aglycones extracting by ethyl acetate and removing the lipophilic
      substances by means of hexanic extraction. The aglycones outcome is not less than
      80%. The preparation obtained contains over 50% of soya bean aglycones.

PMID- 14964877
TI  - [Infection, autoimmune diseases, atherosclerosis, infarct, stroke,
      cancerogenesis: what is in common].
AB  - The problem of the transformation of specific antibodies into nonspecific
      polyreactive immunoglobulins (PRIG) was considered. On the basis of the obtained
      data the conclusion has been made that this process can occur not only in vitro,
      but also in vivo. The biological consequences of such a transformation of
      circulated specific antibodies into PRIG or increase of PRIG reactivity because
      of their unblocking are discussed. It was supposed that PRIG was able to play
      positive role in the defence of organisms against some infections. Meanwhile,
      disregulation of the PRIG production in vivo can, probably, lead to their
      participation in induction and/or in aggravation of some danger diseases, such as
      autoimmune diseases, atherosclerosis, infarct, stroke, and cancer. If so, farther
      investigation of PRIG involvement in these pathological processes could open new
      ways for their curing or even prophylaxis.

PMID- 14964878
TI  - [It is the psychiatrists who have compiled all the conditions of psychotherapy
      effectiveness].

PMID- 14964879
TI  - [Total incomprehension of the profound sense of psychotherapy].

PMID- 14964881
TI  - [Second accreditation procedure, towards the evaluation of health services
      quality given to the patient].

PMID- 14964882
TI  - [Management of risks and violence].

PMID- 14964883
TI  - [Laughter and humor, a serious affair?].

PMID- 14964884
TI  - [Helpful laughter and psychotherapy].

PMID- 14964885
TI  - [Mossieu Gaga or the humor in madness].

PMID- 14964886
TI  - [Histories of laughter].

PMID- 14964887
TI  - [Caring at a therapeutic distance].

PMID- 14964888
TI  - [Learning the function of laughter. Interview by Christian Bourdeux].

PMID- 14964889
TI  - [Try a joyful encounter with yourself and others].

PMID- 14964890
TI  - [Post-partum blues and post-natal depression].

PMID- 14964891
TI  - [The labyrinth of specialization].

PMID- 14964892
TI  - [Anorexia and bulimia: a self help group experience].

PMID- 14964893
TI  - [Solidarity reform for dependent persons. A new branch of social protection, but
      without the fifth risk].

PMID- 14964894
TI  - [Reform of home nursing care services, a sea serpent?].

PMID- 14964898
TI  - [Paying attention to the elderly patient's skin].

PMID- 14964899
TI  - [Elderly skin, old skin or parchment?].

PMID- 14964900
TI  - [Esthetic care in the elderly, techniques and benefits].

PMID- 14964901
TI  - [Benefits of thermal baths].

PMID- 14964903
TI  - [Non-drug management of pain. 1/2--Physical therapies].

PMID- 14964904
TI  - [Volunteers in geriatrics].

PMID- 14964905
TI  - [Geriatrics! Did you say geriatrics?].

PMID- 14964906
TI  - [Bloody diarrhea in the elderly patient].

PMID- 14964907
TI  - Narrative medicine--a novel approach.

PMID- 14964908
TI  - Na Kauka O Hawaii. William Hillebrand MD 1821-1886.

PMID- 14964909
TI  - Calcium intake of Asian and Caucasian adolescents in Hawaii.
AB  - The purpose of this study was to assess calcium intake of Asian and Caucasian
      adolescents in Hawaii, food and beverage sources of calcium, and key factors
      influencing calcium intake. Data were gathered in a cross-sectional survey of 51
      adolescents and included two 24-hour recalls per person. Mean calcium intakes
      were below the U.S. Dietary Reference Intake's Adequate Intake level for calcium;
      still, they were higher than nationally reported calcium intakes of this age
      group. Although ethnic differences in dietary calcium intake were not seen
      between the Asian and Caucasian/Other group, the sample size may not be large
      enough to demonstrate a difference. Asians in Hawaii consumed more calcium than
      in previous studies. Caucasian/Other group consumed more non-fat milk than the
      Asian adolescent group. The Caucasian/Other group and the higher socio-economic
      group consumed more calcium from dietary supplements than Asians and the lower
      socioeconomic group. A higher calcium intake was found on the weekday in
      comparison with the weekend (Sunday), which was largely due to calcium intake
      from school meals.

PMID- 14964910
TI  - External cephalic version after rupture of membranes in early labor.
AB  - BACKGROUND: Breech presentation occurs in approximately 4% of term pregnancies.
      Recently the American College of Obstetrics and Gynecology has suggested that
      cesarean section is the safest option if the fetus remains in breech position. As
      an alternative to cesarean section, external cephalic version has been used prior
      to labor and even recently in the patient with rupture of membranes not in labor.
      We present two cases found at our institution from 1990 through 2001, who at term
      presented in early labor with spontaneous rupture of membranes and underwent
      successful external cephalic version. CASE: Two women presented to labor and
      delivery with spontaneous rupture of membranes and were found to be in early
      labor with cervical dilatation. Both underwent successful external cephalic
      version. As labor progressed, each ultimately underwent cesarean section to
      accomplish delivery. One patient underwent cesarean section for failure to
      progress and the other for severe variable decelerations associated with an
      umbilical cord prolapse. CONCLUSION: External cephalic version is possible in the
      term pregnancy with ruptured membranes and in early labor, but the patient
      remains susceptible to complications of version and labor.

PMID- 14964911
TI  - Acute generalized pustular psoriasis presenting with erythroderma associated with
      shock and acute renal failure.
AB  - Acute generalized pustular psoriasis is an uncommon but dangerous form of
      psoriasis with a systemic presentation. Acute exacerbation, an early picture of
      acute generalized pustular psoriasis (AGPP), can be fatal, therefore, early
      recognition and systemic therapy is critical. It is an important differential
      diagnosis of erythroderma. Epidemiology, etiology, diagnosis, and treatment
      options are discussed in this paper.

PMID- 14964912
TI  - A thirty-five-year-old woman with oral and genital ulcers, pustular skin lesions,
      and polyarthritis.

PMID- 14964913
TI  - The University of Hawaii Telemedicine Project: a Web-based telemedicine
      curriculum for health care providers.

PMID- 14964914
TI  - A new standardized food grouping system facilitates studies of diet and chronic
      diseases.

PMID- 14964915
TI  - Safety of revaccination of patients affected by the oculo-respiratory syndrome
      (ORS) following influenza vaccination.

PMID- 14964916
TI  - Scientists mine for genetic sources of cancer.

PMID- 14964917
TI  - FDA approves groundbreaking Alzheimer's drug.

PMID- 14964918
TI  - Advancing the cause for clinical trials with the elderly.

PMID- 14964919
TI  - Navigating the hospice benefit.

PMID- 14964920
TI  - A focus on hope over hardship.

PMID- 14964921
TI  - Taking the pulse of employees.

PMID- 14964922
TI  - The changing metropolitan designation process and rural America.
AB  - In June 2003, the Office of Management and Budget (OMB) released new county-based
      designations of Core Based Statistical Areas (CBSAs), replacing Metropolitan
      Statistical Area designations that were last revised in 1990. In this article,
      the new designations are briefly described, and counties that have changed
      classifications are identified. The new designations identify 2 categories of
      counties or county clusters within CBSAs: Metropolitan Statistical Areas and
      Micropolitan Statistical Areas. Counties designated as neither are simply
      referred to as "outside Core Based Statistical Areas." Among counties classified
      as metropolitan in 1999, 94% are still classified as such, 5% are now
      micropolitan, and 0.7% are outside CBSAs. The majority of counties that were
      nonmetropolitan in 1999 remain outside CBSAs (60%), while 28% are now classified
      as micropolitan and 12% have become metropolitan. The percentage of counties
      classified as metropolitan has increased from 27.2% to 34.7%, and the population
      identified as residing in these areas increased from 81% of the total US
      population to 83%. Some interpretation difficulties may arise in the future, as
      the naming system lends itself to lumping metropolitan and micropolitan together
      because of their common designation as CBSAs. The central problem to this
      classification scheme is that it tracks the urban growth of the nation and its
      tendency toward agglomeration of markets but pays little attention to the places
      that are outside CBSAs altogether.

PMID- 14964923
TI  - Rural-urban differences in the social climate surrounding environmental tobacco
      smoke: a report from the 2002 Social Climate Survey of Tobacco Control.
AB  - CONTEXT: Although previous research has found smoking rates to be higher among
      residents of rural areas, few studies have investigated rural-urban differences
      in exposure to environmental tobacco smoke (ETS). OBJECTIVE: This study
      contrasted the social climate surrounding ETS among Americans who resided in 5
      levels of county urbanization. DESIGN: Data were collected via telephone
      interviews administered to a representative sample of 3,009 civilian,
      noninstitutionalized adults over age 18 in the United States. Households were
      selected using random digit dialing procedures. FINDINGS: Compared to residents
      of urban counties, rural residents reported fewer restrictions on smoking in the
      presence of children and lower incidences of smoking bans in households, family
      automobiles, work areas, convenience stores, fast-food restaurants, and
      restaurants. Interestingly, when rural-urban variations in knowledge and
      attitudes about ETS were examined, the magnitude of rural-urban differences was
      smaller or nonexistent for these indicators. Moreover, logistic regression models
      indicated that none of these rural-urban differences in knowledge and attitudes
      persisted after statistically controlling for region, smoking status, gender,
      race, age, and education factors. This suggests that the observed rural-urban
      differences in ETS bans could not be explained adequately by rural-urban
      differences in knowledge and attitudes about the dangers of ETS. CONCLUSIONS: The
      policy implications of this research point to a greater need in rural America for
      programs focusing on the restriction and elimination of ETS. They also suggest
      that programs focusing only on influencing the levels of ETS knowledge and
      attitudes among the general population may not be adequate in producing the
      desired change.

PMID- 14964924
TI  - Insurance coverage of prescription drugs and the rural elderly.
AB  - CONTEXT: Rural impacts of a Medicare drug benefit will ultimately depend on the
      number of elderly who are currently without drug coverage, new demand by those
      currently without coverage, the nature of the new benefit relative to current
      benefits, and benefit design. PURPOSE: To enhance understanding of drug coverage
      among rural elderly Medicare beneficiaries and their expenditures for
      pharmaceuticals. METHODS: Estimates of the extent of coverage, expenditures, and
      sources of drugs were obtained using data are from the 1997 Medicare Current
      Beneficiary Survey and the Pharmacy Verification and Household Components of the
      1996 Medical Expenditure Panel Survey. FINDINGS: Three-quarters of the urban
      elderly had some type of drug coverage in 1997 versus 59% of the elderly in rural
      areas. Urban residents were more likely to have obtained their drug coverage from
      an employer-sponsored supplemental plan, and rural residents were more likely to
      have self-purchased Medigap drug coverage. Expenditures and use of drugs by
      Medicare beneficiaries are greater for those with than without coverage, and
      differences are invariant with respect to geographic location. Coverage under
      self-purchased supplemental plans appears less generous than under employer
      sponsored plans in both rural and urban areas. Rural and urban elderly are more
      than twice as likely to receive at least 1 prescribed medication through the mail
      than the general population. CONCLUSION: A well-designed Medicare drug benefit
      would be especially beneficial to the rural elderly because relatively more rural
      elderly currently lack coverage or have less generous coverage than urban
      beneficiaries. Mail-order distribution may help contain future program
      expenditures.

PMID- 14964925
TI  - Improving rural cancer patients' outcomes: a group-randomized trial.
AB  - CONTEXT: Significant barriers exist in the delivery of state-of-the-art cancer
      care to rural populations. Rural providers' knowledge and practices, their rural
      health care delivery systems, and linkages to cancer specialists are not optimal;
      therefore, rural cancer patient outcomes are less than achievable. PURPOSE: To
      test the effects of a strategy targeting rural providers and their practice
      environment on patient travel for care, satisfaction, economic barriers, and
      health-related quality of life. METHODS: A group-randomized trial was conducted
      with 18 rural communities in the north-central United States. Twelve of these
      communities were included and defined as the unit of analysis for the patient
      outcomes portion of the study. The intervention targeted rural providers and
      their practice environment. The subjects were patients with breast, colorectal,
      lung, and prostate cancers from the rural communities. The main outcomes were
      patients' travel to obtain health care, satisfaction with care, perceptions of
      economic barriers to care, and health-related quality of life. In total, 881
      patients were included. RESULTS: Group randomization was balanced. Travel for
      health care was significantly reduced in the community group exposed to the
      intervention during months 13 to 24 following cancer diagnosis. The mean miles
      traveled per patient were 1,326 (SE = 306) for the experimental group and 2,186
      (SE = 347) for the control group (P = 0.03). No significant differences in
      satisfaction with care, economic barriers to care, or health-related quality of
      life were found. CONCLUSIONS: The intervention significantly reduced cancer
      patient travel for health care, which suggests that access to care improved in
      the experimental group. The results of this study do not allow conclusion that
      there was no effect on other patient outcomes. The results supported the study's
      conceptual framework and many of its hypotheses.

PMID- 14964926
TI  - Office systems and their influence on mammography use in rural and urban primary
      care.
AB  - CONTEXT: Breast cancer screening rates are lower in rural communities. Although
      studies have addressed barriers to mammography for rural residents, physician
      practice barriers have received less attention. PURPOSE: Controlled clinical
      trials have shown that the use of office reminder systems in primary care
      practices is related to increased clinical care rates. Therefore, we compared
      office systems use in primary care practices located in rural and urban
      communities and assessed the impact of these systems on rural-urban differences
      in mammography utilization. METHODS: We identified female Kansas Medicare
      beneficiaries aged 65 to 79 from Medicare claims data (N = 24,030) and determined
      which beneficiaries received a mammogram between April 1, 1999, and March 31,
      2001. We linked beneficiaries to their primary care providers and obtained
      surveys from 180 primary care practices on their use of office reminder systems.
      FINDINGS: Mammography rates ranged from 20% to 92% (mean = 65%) among the 180
      practices. Flowsheets with a mammography prompt were used by 33% of the
      practices, 38% utilized nonphysician staff to identify women due for mammograms,
      and 15% used computerized reminder systems. Urban practices used flowsheets more
      often than rural practices (44% versus 16%, P < 0.001). A multivariable
      regression model demonstrated higher mammography rates in urban practices, group
      practices, and practices using mammography flowsheets. CONCLUSIONS: Despite
      success in randomized controlled trials, reminder systems are not used often by
      primary care providers and are used even less often in rural compared to urban
      practices. Consistent implementation may be a major barrier to the successful
      adaptation of flowsheets by primary care offices.

PMID- 14964927
TI  - Arguing for rural health in Medicare: a progressive rhetoric for rural America.
AB  - Rural health policy is the laws, regulations, rules, and interpretations that
      benefit or affect health and health care for rural populations. This paper
      examines how rural health policy is viewed in the broader field of public policy,
      discusses the role of advocacy in developing rural health policy, and suggests
      ways to make that advocacy more effective. This paper critically reviews policy
      statements and policy positions taken by key opinion leaders and the leading
      stakeholders in rural health policy to determine how advocacy for rural
      communities is expressed. It is not clear how the rural health advocacy coalition
      is viewed by the professional policy world or the public: as an issues network
      pressing for fair and equal treatment or as an interest group seeking special
      advantages. This paper also explores the types of claims that rural advocates
      make in the specific context of Medicare policy to determine to what extent those
      claims reflect a central theme of fairness and inclusiveness in national policies
      versus claims that benefit special interests. The paper suggests that the
      rhetoric of rural advocates can be better structured to advocate for policies on
      the basis of a progressive sense of fairness.

PMID- 14964928
TI  - What doesn't kill you makes you stronger: determinants of stress resiliency in
      rural people of Saskatchewan, Canada.
AB  - PURPOSE: This article discusses a research study that explored how rural people
      in Saskatchewan, Canada, respond to stressful events and adversity, without
      outside interventions. METHODS: In-depth interviews were conducted with 17
      individuals who were living or had lived on a farm in Saskatchewan. The
      participants' definitions of resiliency, their experiences with resiliency or
      lack of resiliency, and what they identified as the barriers to and enhancers of
      resiliency in their lives were discussed. FINDINGS: Resiliency was defined as a
      process and interactive model that included "bouncing back" from adversity,
      coping, and acquiring skills, such as problem solving and learning. Resiliency
      was dynamic, temporal, and relational and was both proactive and reactive. There
      were both internal and external barriers to and enhancers of resiliency. Barriers
      to resiliency included fear, isolation, and depopulation, whereas enhancers
      included resources, support, and control. CONCLUSIONS: Traditional resiliency
      models are not sufficient for understanding resiliency. It is clear that social,
      political, and economic factors play an important role in the resiliency and
      health of people who live in rural areas. A conceptualization of resiliency must
      be embedded in a social context and include community factors. Recommendations
      for enhancing resiliency, such as sustaining rural life, supporting families, and
      providing services, are also discussed.

PMID- 14964929
TI  - Factors associated with health-related quality of life among an older population
      in a largely rural western region.
AB  - CONTEXT: As elderly people become a larger proportion of the rural population, it
      is important to identify those at risk for poor health. Predictors of health
      related quality of life can be useful in designing interventions. PURPOSE: One
      objective of the present study was to profile the health-related quality of life
      of community-dwelling, elderly people in a southwestern region of the United
      States. A related objective was to identify the principal factors associated with
      health-related quality of life, thereby identifying population subgroups in
      greatest need of health or social services. METHODS: A telephone survey of
      approximately 5,000 individuals 65 years and older collected data on need for
      assistance with activities of daily living, physical and mental health-related
      quality of life, and worry about health status measures. A modified version of
      the Behavioral Model was used to more clearly distinguish the different groups at
      risk for poor health. FINDINGS: Those groups of community-dwelling, elderly
      people in the poorest health were older than 75 years, had less than a high
      school education, were retired or unemployed, and had low household income. No
      differences were found by urban, rural, and frontier residence. CONCLUSIONS: To
      maintain the physical, social, and psychological health of older people residing
      in rural and urban areas, social services, medical care, and supportive services
      are needed, particularly among the most socially and economically disadvantaged.

PMID- 14964930
TI  - Views on exercise and physical activity among rural-dwelling senior citizens.
AB  - CONTEXT: This study was conducted with senior citizens in the 2 rural communities
      of Ada and Lindsay, Oklahoma. These communities are both predominantly white,
      with the largest minority population being American Indian. Both communities are
      more than 60 miles from a metropolitan area and have a history of farming and
      ranching. PURPOSE: The purpose of this study was to explore contextual factors
      related to physical activity among senior citizens living in rural communities.
      METHODS: Two focus groups were conducted. The groups were conducted in mixed-sex
      sessions and were audiotaped and transcribed verbatim for the purpose of
      analysis. FINDINGS: Themes from the focus groups included the following: (1) the
      types of daily activities engaged in by seniors; (2) the meaning and connotation
      of the words exercise and physical activity, with physical activity connotating
      for some the negative imagery of physical labor; and (3) the availability and
      suitability of settings for physical activity. For seniors living in rural
      settings in Oklahoma, the lack of indoor facilities and the sometimes extreme
      climatic conditions serve as significant barriers to physical activity.
      CONCLUSION: This study suggests that programs seeking to encourage physical
      activity among seniors in rural areas could benefit from an assessment of
      resources and settings for physical activity and the avoidance of language that
      may have negative connotations for this population.

PMID- 14964931
TI  - A sense of place: rural training at a regional medical school campus.
AB  - CONTEXT: Traditionally, rural students experience urban disruption during the
      many years of education and training in urban environments before choosing a
      practice site. Regional rural campuses that allow students to live and work in
      small towns during the last 2 years of medical school are one strategy to address
      this issue. PURPOSE: To report the results of the first 10 years of a rural
      campus in western Kentucky, including response to difficulties filling openings
      for third- and fourth-year medical students at the campus. METHODS: A survey was
      sent to all 76 students who had shown interest in the rural campus, asking them
      to prioritize the important issues in their campus choice. FINDINGS: Students not
      choosing the rural campus placed a higher priority on large-city amenities,
      better opportunities for their spouse, and proximity to family in eastern and
      central Kentucky. Students who chose the rural campus placed a higher priority on
      one-on-one clinical training and interest in small town life. CONCLUSIONS: For
      the rural clinical campus to reach its potential, more rural students from the
      western part of the state must be admitted to medical school and then choose this
      campus. Strategies to reinforce the sense of place among rural students focus on
      experiential programs in rural areas. Initial results suggest that medical
      educators should consider geography more carefully when designing approaches to
      address physician maldistribution.

PMID- 14964932
TI  - Rural-urban comparisons of nursing home residents with multiple sclerosis.
AB  - CONTEXT: Multiple sclerosis (MS) is the most common neurologic disease that
      disables younger adults, affecting as many as 350,000 Americans. PURPOSE: The
      objectives of this study are to develop profiles of nursing home residents with
      MS from rural areas and compare them to residents with MS who lived in urban
      areas, suburban areas, and large towns. METHODS: We analyzed all admission
      assessments for residents with MS (13,357 assessments) in the Minimum Data Set
      between June 23, 1998, and December 31, 2000, that also had the resident's ZIP
      code of primary residence before admission. FINDINGS: Urban and rural comparisons
      of residents with MS demonstrate a range of significant demographic differences.
      Significantly greater proportions of MS residents from rural areas exhibited a
      sense of initiative or involvement in activities of the nursing facility compared
      with residents with MS from urban and suburban areas. The differences in the
      utilization of physical and occupational therapies were striking, with MS
      residents from rural areas averaging significantly fewer minutes of these
      therapies. We also found that MS residents from rural areas averaged fewer
      minutes of psychological therapy in the nursing facility and also were less
      likely to have seen a licensed mental health specialist than MS residents from
      urban areas. CONCLUSIONS: Nursing home residents with MS from rural areas receive
      fewer therapies and less mental health care than residents with MS from other
      areas.

PMID- 14964933
TI  - Rural policy development: an NRHA and PACE association collaborative model.
AB  - The Program of All-Inclusive Care for the Elderly (PACE) offers a unique model of
      comprehensive care for frail, elderly people. To date, all of the PACE programs
      have been located in urban areas. Rural advocates and policymakers, however,
      believe the program may hold great promise for use in rural areas, which have
      higher percentages of elderly residents than urban areas. In 2002, the National
      Rural Health Association and the National PACE Association convened a meeting
      that brought together PACE experts, policymakers, and rural health care providers
      to examine PACE and its applicability for rural communities. The meeting
      participants concluded that there were many rural communities where the PACE
      model might not only be appropriate but also highly successful in caring for
      rural, frail, elderly people. This article examines the notion of expanding the
      PACE model to rural communities, including some of the barriers and some of the
      possible solutions that might make PACE a viable part of the rural health care
      delivery system.

PMID- 14964934
TI  - A life lived at the crossroads of knowledge and children's policy.

PMID- 14964935
TI  - Where are you from? Child advocacy and the benefits of marginality.

PMID- 14964936
TI  - From research to policy: choosing questions and interpreting the answers.

PMID- 14964937
TI  - Risk and prevention: building bridges between theory and practice.

PMID- 14964938
TI  - Creating culturally sensitive and community-sensitive measures of development.

PMID- 14964939
TI  - Adherence process research on developmental interventions: filling in the middle.

PMID- 14964940
TI  - The necessity of teacher development.

PMID- 14964941
TI  - The role of psychological research in setting a policy agenda for children and
      families.

PMID- 14964942
TI  - Parent-adolescent communication about sex and birth control: a conceptual
      framework.

PMID- 14964943
TI  - Beyond the yes-no question: measuring parent-adolescent communication about sex.

PMID- 14964944
TI  - Talking to a tiger: fathers reveal their difficulties in communicating about
      sexuality with adolescents.

PMID- 14964945
TI  - "It's a Catch-22": same-sex-attracted young people on coming out to parents.

PMID- 14964946
TI  - Interventions designed to promote parent-teen communication about sexuality.

PMID- 14964947
TI  - Keeping the record straight.

PMID- 14964948
TI  - The effects of leupeptin on cochlear blood flow, auditory sensitivity, and
      histology.
AB  - The purpose of this study was to evaluate the long-term safety of administering
      leupeptin (1 mg/ml in Hank's Balanced Salt Solution) to the round window membrane
      by investigating its effects on cochlear blood flow, auditory sensitivity (i.e.,
      auditory brainstem response), and cochlear histology. A comparison of baseline
      and posttreatment measurements of cochlear blood flow and mean arterial blood
      pressure in guinea pigs revealed no significant changes. Auditory brainstem
      response measurements revealed no significant changes in auditory threshold
      shifts when compared to controls at the 2-, 4-, 6-, and 8-week time points.
      Furthermore, poststudy surface preparations of the organs of Corti and
      cytocochleograms from leupeptin-treated ears and controls revealed no significant
      hair cell losses. These data suggest that the prolonged administration of
      leupeptin (1 mg/ml at a rate of 0.5 microliter/hr for 8 weeks) to the round
      window membrane is not ototoxic. This study may serve as a basis for future
      clinical trials of leupeptin administration for the prevention or treatment of
      noise-induced hearing loss and the management of tinnitus.

PMID- 14964949
TI  - Vestibular impairment.
AB  - The measurement of vestibular impairment for medicolegal purposes represents a
      challenge. In the United States, the most widely employed system is that
      described in the American Medical Association's (AMA's) Guides to the Evaluation
      of Permanent Impairment. The fourth edition, published in 1993, represented a
      major step forward at that time, but room for improvement still exists. The
      problem areas in the Guides are discussed and appropriate modifications are
      suggested. Briefly, balance disorders are divided into two general categories,
      constant and recurrent (episodic). Using this novel approach, scales for
      quantification of the symptoms and signs (and laboratory tests for each), in
      increasing order of severity, are suggested. In this manner, an overall score may
      be derived for any individual with a permanent medicolegal balance impairment.

PMID- 14964950
TI  - Development of the psychological impact of tinnitus interview: a clinician
      administered measure of tinnitus-related distress.
AB  - The development of valid and reliable methods for assessing psychological aspects
      of tinnitus continues to be an important goal of research. Such assessment
      methods are potentially useful in clinical and research contexts. Existing self
      report measures have a number of disadvantages, and so a need exists to develop a
      form of assessment that is less open to response bias and the effects of
      experimental demand. A new approach, the Psychological Impact of Tinnitus
      Interview (PITI), is described, and some preliminary data on its psychometric
      properties are reported. The results suggest that the PITI is capable of
      providing a measure of separate, relatively independent dimensions of tinnitus
      related distress--namely, sleep difficulties, general distress, mood, suicidal
      aspects, and avoidance of or interference with normal activities. This method may
      lead to more refined measures of these dimensions of tinnitus-related
      psychological difficulties. The PITI should be regarded as a promising assessment
      tool for use in experimental settings, pending further work on its content,
      coding method, and administration.

PMID- 14964951
TI  - Vestibulotoxicity and ototoxicity of gentamicin in newborns at risk.
AB  - Gentamicin is a potentially ototoxic drug routinely used for treatment of life
      threatening infectious diseases in neonatology. In study 1, of 8,333 children
      examined for hearing disorders, 134 (1.6%) had received previous treatment with
      gentamicin. Only eight (6.0%) suffered from various extents of sensorineural
      hearing impairment, and all eight had a history of other risk factors of hearing
      loss (e.g., perinatal asphyxia, acidosis, icterus gravis, or meningitis). In
      study 2, 30 children (mean age, 13.2 months) with normal hearing had received
      gentamicin during the newborn phase, and 30 healthy children of similar age
      without previous gentamicin treatment were examined for vestibular function.
      Neither in the number of spontaneous eye movements nor in the means of the
      nystagmus parameters of the rotatory test did the data show any significant
      difference between the groups. The results indicate that gentamicin in controlled
      therapeutic doses has a less ototoxic and vestibulotoxic effect in newborns than
      it does in older children or in adults.

PMID- 14964952
TI  - Temporary cerebral histic hypoxia in simulated microgravity.
AB  - The authors determined in their previous examinations that the vertical component
      of diagonal optokinetic nystagmus (DOKN) decreases considerably more in the
      conditions of hypoxia and antiorthostatic posture than does the horizontal
      component. Relying on these findings, they reasoned that the tectal and pretectal
      gaze centers, which organize vertical eye movement, are more sensitive to both
      hypoxia and antiorthostatic posture than is the pontine gaze center, which
      directs horizontal eye movement. In their present examinations, the authors
      sought to discover how cranial shifting of body fluids alters the DOKN and
      cardiopulmonary dynamics. They established that, at-30-degree antiorthostatic
      posture during 3 hours' loading, the diminution of pulse rate and systolic blood
      pressure is accompanied by continuous enhancement of diastolic blood pressure,
      diminishment of the carbonometric value, and augmentation of respiratory rate.
      The disturbances of DOKN, which mimicked previous similar findings under
      conditions of hypoxia and antiorthostatic posture, may be caused by the
      hypocapnia that is induced by antiorthostatic posture and that produces histic
      hypoxia. However, hypocapnia does not exclude the possibility of cerebrovascular
      injury, which was detected during animal experiments in microgravity or in
      simulated microgravity. To resolve this issue ultimately, further investigations
      are necessary.

PMID- 14964953
TI  - Electroencephalographic changes induced by a noise generator in tinnitus patients
      and healthy controls.
AB  - The present study was conducted in an attempt to determine whether noise
      generators (NGs) induce changes of electroencephalographic activity in healthy
      control subjects and in subjects suffering from tinnitus. The results indicated
      that the application of an NG, irrespective of its placement, induced a
      significant increase of the average total power in both the female and male
      tinnitus groups. However, no significant changes were observed for the male
      control group. A weak increase of average total power was noted for the female
      control group with the NG placed either in the left or the right ear. The NG
      induced significant changes of average power in different frequency bands. In
      conclusion, the NG-induced electroencephalographic changes were dependent on
      gender, tinnitus location, and placement of the NG.

PMID- 14964954
TI  - A totally implantable drug delivery system for local therapy of tinnitus.

PMID- 14964955
TI  - Morphological and functional study of the cochlea after administration of
      estrogen and progesterone in the guinea pig.
AB  - The aim of this study was to analyze the morphological cochlear changes and
      auditory function observed after the administration of estrogen or progesterone
      or both. Sixty-two guinea pigs were divided into four groups that received
      estrogen (group 1), progesterone (group 2), estrogen and progesterone (group 3),
      and saline solution (controls, group 4), respectively. The auditory evaluation
      consisted of brainstem evoked response audiometry, performed before and after
      drug administration. Structural analysis was based on histological hematoxylin
      and eosin staining preparations. Our results showed changes in latency and
      amplitude of waves in the study groups that received estrogen or progesterone.
      The main histological changes observed were inflammatory infiltrate and
      vacuolization of the stria vascularis. Our results suggest that both estrogen and
      progesterone lead to morphological and physiological lesions of the cochlea, the
      degree of the observed lesions depending not only on the presence of these
      hormones but also on the proportion between them.

PMID- 14964956
TI  - Treatment of cochlear tinnitus with transtympanic infusion of 4% lidocaine into
      the tympanic cavity.
AB  - Tinnitus is an otological symptom that is encountered often, yet its treatment is
      difficult. If tinnitus is of cochlear origin, a reasonable assumption is that a
      total depression of the cochlear function will abolish cochlear tinnitus. To
      achieve this depression, transtympanic infusion of a local anesthetic (4%
      lidocaine) to anesthetize the inner ear was conducted in a patient suffering from
      tinnitus. Transtympanic infusion of 4% lidocaine was performed as a treatment for
      cochlear tinnitus, and its efficacy was investigated. The overall efficacy rate
      for the 292 patients with 369 affected ears was 81%. In the investigation of the
      treatment results in cases of different underlying ear diseases, the efficacy
      rate was high for tinnitus accompanying sudden deafness and labyrinthine vertigo.
      However, vestibular symptoms, such as vertigo and nausea, developed after
      lidocaine infusion. No permanent side effects were noted. Lidocaine infusion is
      thought to be a useful treatment option for tinnitus and should be considered
      before surgical treatment. Inner ear anesthesia into the tympanic cavity has been
      carried out in patients who had cochlear tinnitus and in whom conservative
      methods of therapy, such as oral medication, had proved unsuccessful. This
      treatment method is useful as a local therapy for cochlear tinnitus.

PMID- 14964957
TI  - Metabolic disorders in vertigo, tinnitus, and hearing loss.
AB  - Vertigo, tinnitus, and hearing loss are common complaints among populations of
      industrial countries, especially in persons older than 40 years. Numerous agents
      are known to incite vertigo, tinnitus, and hearing loss, among them
      hyperinsulinemia, diabetes mellitus, and hyperlipidemia. In this study, we
      proposed to assess the occurrence of hyperinsulinemia, diabetes mellitus, and
      hyperlipidemia in patients suffering from vertigo, tinnitus, or hearing loss of
      unknown origin. Results of various tests in 48 patients were compared to those in
      31 control subjects. Assessments of body mass index, blood pressure, and
      laryngological, audiometric, and electronystagmographic parameters were performed
      in all study participants. An oral glucose tolerance test was used to evaluate
      insulin levels, and lipoprotein phenotyping served to determine cholesterol,
      triglyceride, and lipoprotein levels. Patients were found to be significantly
      more overweight (on the basis of body mass index) than were the control subjects.
      Hypertension was more common among patients than controls, but the difference was
      significant only between the men in the two groups. Disturbances of glucose
      metabolism were found in 27.1% of patients but in only 9.7% of controls. Diabetes
      mellitus was not present in any controls but was identified in four patients.
      Hyperinsulinemia was almost twice as common in patients as in controls. Only the
      occurrence of hyperlipoproteinemia seemed not to differ between patients and
      control subjects. We conclude that such disturbances of glucose metabolism as
      diabetes mellitus and hyperinsulinemia may be responsible for inner ear diseases,
      whereas the role of disturbances of lipid metabolism remains vague.

PMID- 14964958
TI  - Tinnitus as a prognostic sign in idiopathic sudden sensorineural hearing loss.
AB  - Idiopathic sudden sensorineural hearing loss remains a controversial problem with
      respect to etiology and the factors that might predict a favorable prognosis.
      This study evaluated the possible prognostic factors of recovery in 67 patients
      with idiopathic sensorineural hearing loss treated with steroids (prednisone),
      plasma expanders (intravenous dextran), and vasodilators (papaverine). Clinical
      recovery was estimated by contrasting the audiometric results on admission and
      those at discharge 10 days later. The correlation between various potential
      prognostic factors and audiological improvement was calculated. Only two factors
      were found to be associated significantly with hearing improvement: tinnitus (p <
      .04) and the slope of audiogram on admission (p < .045). Tinnitus and the
      presence of an ascending audiogram were found to be correlated with a favorable
      outcome in idiopathic sensorineural hearing loss.

PMID- 14964959
TI  - [Cutaneous pseudolymphomas].
AB  - Histological and immunohistochemical characteristics of principal types of skin
      pseudolymphomas, their differential diagnosis with true skin lymphomas are
      outlined.

PMID- 14964960
TI  - [Morphological diagnosis of the inhalation trauma and criteria of efficacy of the
      endobronchial laser therapy based on the biopsy material].
AB  - The results of 424 biopsies obtained at fibrobronchoscopy (FBS) from 45 patients
      with inhalation trauma (IT) are presented. The standard and endoscopic laser
      treatment (ELT) have been used (24 and 21 patients, respectively). It is
      demonstrated that precise visual assessment of IT severity is possible under
      dynamic endoscopic observation only. Healing of mucous defects of the tracheo
      bronchial tree was shorter in the ELT group. Morphologically, early and
      continuous ELT was not associated with signs of severe purulent inflammation and,
      therefore, produced no early additional, damage to the wall. This may explain
      accelerated formation of the granulation tissue at the ulcer bottom and
      epithelization at the margin areas.

PMID- 14964961
TI  - [The role of Fas/FasL system in induction of hepatocyte apoptosis in chronic
      viral hepatitides].
AB  - The aim of the study was assessment of hepatocyte apoptosis depending on
      expression of Fas and FasL proteins by various liver cells in patients with
      chronic viral hepatitis B (CVHB) or chronic viral hepatitis C (CVHC). The
      symptoms of hepatocyte apoptosis were observed in 3 of 12 patients with CVHB and
      in 9 of 14 patients with CVHC, the proportion of apoptotic cells being 12-65%.
      Hepatocytes of healthy people and patients with hepatitis B or C express Fas
      protein in the cytoplasm diffusely, as granules or on cell membrane. In health,
      hepatocytes do not express FasL, but in CVH they do. The highest apoptosis was
      observed in Fas protein location as granules in cytoplasm or in their preferable
      location on the cell membrane. The severity of hepatocyte apoptosis in CVH
      directly correlated with FasL expression by the cells of the lymphoid-histiocytic
      infiltrate in the liver and inversely correlated with FasL expression by
      hepatocytes. Thus, a great part of hepatocytes in CVH are killed by the virus;
      Fas/FasL interaction is leading in damage to hepatocytes in CVH.

PMID- 14964962
TI  - [Clinico-morphological assessment of early and late results of laser therapy of
      the anastomosis area after radical surgeries for stomach cancer].
AB  - The study included 52 patients after gastrectomy for carcinoma of the proximal
      part of the stomach. Endoscopic laser therapy was made in 32 patients to reduce
      inflammation in the anastomosis zone 2-3 weeks after surgery. Drug therapy was
      made in 20 patients within the same time period. Histochemical study of the
      biopsy material of esophageal and intestinal part of the anastomosis was carried
      out. It is revealed that application of copper vapor laser early after surgery
      reduces edema and inflammation in the anastomosis zone for 2 weeks as well as
      accelerates the growth of granulation tissue forming a delicate scar thus
      preventing formation of scar stenosis.

PMID- 14964963
TI  - [The role of apoptosis and proliferation of epitheliocytes in morphogenesis of
      Helicobacter pylori-associated gastritis].
AB  - 77 patients with chronic Helicobacter gastritis verified endoscopically and
      exacerbation of duodenal ulcer were examined. H. pylori infection was identified
      by the rapid ureasa test (CLO-test) and Giemza staining. The patients received 7
      day three-component therapy for eradication of H. pylori. Apoptosis and
      proliferation were studied in 16 patients in serial sections with the use of
      monoclonal antibodies. Eradication of H. pylori resulted in relief of
      inflammation and transformation of active gastritis in inactive one. H. pylori
      associated gastritis is associated with activation of apoptosis of gastric mucosa
      epithelial cells and epitheliocytes proliferation. H. pylori eradication alters
      correlation between apoptosis of epitheliocytes and their proliferation:
      successful eradication of the infection decreases apoptosis, high proliferative
      activity of epitheliocytes persists reflecting enhancement of regeneration in
      gastric mucosa.

PMID- 14964964
TI  - [Morphofunctional characteristics of arterial bed in exacerbation of
      gastroduodenal ulcer disease and chronic pancreatitis].
AB  - Samples of the stomach, duodenum and pancreas removed from 76 patients obtained
      during organ-preserving operations for ulcer and chronic pancreatitis were
      examined morphologically. It is found that the most frequent type of changes in
      the intraorgan arteries is their wall hypertrophy in combination with
      hyperelastosis and elastotic fibrosis. This characterizes chronic local arterial
      hypertension. An additional morphological symptom complex caused by a vegetative
      vascular crisis is formed in the arteries of the damaged organ in exacerbation of
      the disease. The complex includes prominent dystonic and alterative changes of
      small arteries leading to stasis and thrombogenesis in the microvessels. Unknown
      so far phenomenon of arterial invagination in 18 patients was observed. It leads
      to a complete block of circulation, acute ischemia followed by tissue necrosis
      which was most typical for ulcer exacerbation and chronic pancreatitis.

PMID- 14964965
TI  - [Morphological characteristics of inflammatory polyps of the large intestine in
      children].
AB  - Inflammatory polyps of 32 children were studied morphologically. Inflammatory
      polyps comprised more than 20% of all removed polyps in 1983-2002. They were
      second among common polyps in children after juvenile polyps. Typical location of
      inflammatory polyps was the rectum. Characteristic morphological features of
      inflammatory polyps in children are predomination of the inflammatory component
      represented by granulation tissue. In contrast to juvenile polyps granulation
      tissue in inflammatory polyps does not contain glands but may contain foreign
      bodies and giant cells. About one third of the inflammatory polyps in children in
      this study was associated with mucosal prolapse syndrome evidenced by
      proliferation of smooth muscle cells and fibrous tissue in the stroma of polyp
      glandular component.

PMID- 14964966
TI  - [Using telepathology for remote pathoanatomical diagnostics].
AB  - The experience accumulated in 2000-2002 in the department of pathology of the
      central clinical hospital of President Administration Medical Centre on the use
      of telepathology for distant anatomopathological diagnosis is reviewed.
      Multilevel consulting-diagnostic telepathological network having local
      (intrahospital and city), federal and international levels was created in the
      scope of the departmental telemedical project. The results of the use of removed
      telediagnosis for urgent histological studies on frozen sections indicate the
      absence of differences between this method and conventional optical diagnosis.

PMID- 14964967
TI  - [Gsell-Erdheim syndrome: main pathomorphological alterations].
AB  - 24 cases of Gsell-Erdheim syndrome observed in 1999-2001 have been analysed.
      There were 20 men (83.4%) and 4 women (16.6%) aged 22-69 years. Six men (25%)
      died at the age under 50 years. At necropsies the following characteristic
      variants of stratification were observed: a total damage with stratification of
      the aorta at all length or, less often, local damage. Destruction of an elastic
      skeleton of the media is the basis of aorta stratification: zones free of the
      nuclei, foci of elastolysis (medianecrosis), thinning, dyschromia and
      fragmentation of elastic fibers, focal hyperelastosis. The pathological process
      involves all the aortic length not only the area of aneurysm and rupture.
      Manifestations of variable severity of the same process were seen in different
      parts of the aortic wall.

PMID- 14964968
TI  - [Morphological characteristics of the kidneys in fetuses and newborns exposed to
      hypoxia].
AB  - A pathomorphological study of the kidney in embryos and newborns was carried out
      (149 cases). Correlations were found between morphological characteristics and
      duration of hypoxia.

PMID- 14964969
TI  - [Hashimoto and de Quervain thyroiditis].
AB  - 117 thyroids from patients with autoimmune and nonautoimmune thyroiditis were
      investigated. The conclusion about morphofunctional state of the thyroids from
      patients with autoimmune and nonautoimmune thyroiditis were made on the basis of
      macroscopical, histological, morphometrical and immunohistochemical findings.

PMID- 14964970
TI  - [Bone marrow alterations in sarcoidosis].
AB  - Trepanobiopsy of the bone marrow followed by a histological study was performed
      in 3 patients with sarcoidosis diagnosed in peripheral lymph node (LN) biopsies.
      Granulemas revealed in trepanobiopsies were identical to those found in LN.
      Trepanobiopsy is advisable in patients with sarcoidosis having some changes in
      hemogram.

PMID- 14964971
TI  - [Granulomatous thymitis with stromal amyloidosis].
AB  - In a surgically removed thymus of an 18 year old man granulomatous thymitis with
      lymphoid follicles, amyloidosis, pseudocysts were observed. Rare occurrence of
      this pathology, difficulty of the diagnosis, absence of the treatment concept
      make surgery a method of choice.

PMID- 14964972
TI  - [Diffuse neurofibroma invading the spinal cord channel and soft tissues of the
      chest].
AB  - A case report of a child of 11 years of age. The patient is in a good condition
      two years after surgery.

PMID- 14964973
TI  - [Formalized macroscopic description and computer analyser of macroscopic image
      (as illustrated by gastric pathology)].
AB  - A computer analyzer is regularly used in the department of pathology in
      formalized macrodescription of the stomach. Advantages of this method are
      described.

PMID- 14964974
TI  - To err is human--the fallible physician.
AB  - A 1999 report published by the Institute of Medicine shocked our nation's
      citizens and health care providers. This report, entitled To Err is Human:
      Building a Safer Health System, suggested that as many as 98,000 people die each
      year in the United States as a result of medical errors, making medical errors
      the 8th-leading cause of death. By comparison, Americans are much less likely to
      die from motor vehicle accidents, breast cancer, or AIDS. More Americans die
      annually from medication errors alone than from workplace injuries. Not all
      errors are fatal ones, of course. An error may cause only temporary problems or
      disability, or may have no consequence at all. Errors may be due to mistakes made
      by individual health care providers, or may be due to faulty or inefficient
      processes in organizations and other health care delivery systems. This editorial
      will focus on the inevitability of physician fallibility, two causes of
      individual provider errors, and suggestions for strategies that should be
      considered by health care providers in an attempt to reduce errors. Next month we
      will look at the efforts made by hospitals in order to improve patient safety,
      and how these efforts impact physician practice.

PMID- 14964975
TI  - Postmarketing surveillance and reporting of adverse drug events.

PMID- 14964976
TI  - Why the private practice of medicine furnishes us with the finest possible
      medical care.

PMID- 14964977
TI  - Appendicitis due to tongue stud ingestion: a case study and review of management
      plans.
AB  - Among the causes of appendicitis, foreign body obstruction of the appendiceal
      lumen is one of the rarest. In the majority of cases, swallowed foreign bodies
      pass through the alimentary system without causing any significant disease
      manifestation. Of those items that are swallowed, rigid and/or sharp ones, such
      as needles, have the greatest potential to enter the appendiceal lumen and cause
      an inflammatory reaction with or without perforation. In this case report,
      appendectomy was performed in a patient who was symptomatic after swallowing a
      sharp foreign body.

PMID- 14964978
TI  - State of South Dakota's child: 2003.
AB  - In South Dakota between 2001 and 2002 there was a 2% increase in births with the
      number of both white and minority newborns increasing. In recent decades, trends
      in natality data show an ongoing shift in the ethnic distribution of the state's
      youngest population with 19% of the 2002 births now representing minorities.
      Further, though in recent years there has been a slight increase in the number of
      births, the current yearly birth cohorts represents a 19% decrease from what was
      observed in 1980. The percent of low birth weight newborns (< 2500 g) increased
      in 2002 to 7.2%, however, this rate is lower than the 7.8% rate observed
      nationally, and did not include an increase in very low birth weight (< 1500 g),
      which dropped to below 1% of all births. The South Dakota infant mortality rate
      also dropped to 6.5 in 2002, reflecting a decrease for white infants during both
      the neonatal (< 28 days) and for the post neonatal period of time (29 to 365th
      day of life). For infants of minority ethnicity, there was a decrease in only
      post neonatal mortality with their overall rate of infant death remaining over
      twice that observed for South Dakota's white population. The No Child Left Behind
      Act of 2001 is the special topic of this year's report and includes a discussion
      of how this significant federal legislation is being implemented in South
      Dakota's public schools.

PMID- 14964979
TI  - Understand and apply the nebulizer wisely.

PMID- 14964980
TI  - The function profile of compressed-air and ultrasonic nebulizers.
AB  - In order to study the detailed function of two kinds of nebulizers commonly used
      in clinical asthma treatment, compressed-air and ultrasonic, this study was
      conducted. At the beginning, various flow rates were adjusted, paired with
      different volumes of solutions in the container. The changes of temperature, pH,
      and osmolality during the course of nebulization were examined. Normal saline,
      terbutaline, and fenoterol solutions were used as the nebulized solutions. The
      study was performed in an environment in ambient temperature around 20 degrees C
      and relative humidity around 70%. The results showed a minimal 6 L/min flow rate
      was required to nebulize the solution when using the compressed-air nebulizer.
      The dead volume was about 0.8 ml for compressed-air and 8.5 ml for the ultrasonic
      nebulizer. When using the compressed-air nebulizer, the temperature, both in the
      solution and at the mouthpiece site, dropped gradually. On the contrary, the
      temperatures at both sites increased a little bit when using the ultrasonic
      nebulizer. The pH values of pure terbutaline and fenoterol nebulized solutions
      were acidic (3.58 and 3.00 respectively). The osmolality of terbutaline and
      fenoterol nebulized solutions were isotonic. The osmolality increased gradually
      during the course of nebulization, to a greater extent in the compressed-air
      nebulizer. In conclusion, both types of nebulizers have their special features.
      The ultrasonic nebulizer displays less extent in change of temperature and
      osmolality during nebulization and is expected to be a better device in treating
      asthmatic patients in terms of lesser effect on cooling and changing the
      osmolality of airway mucosa.

PMID- 14964981
TI  - Management of foreign body ingestion in children: experience with 42 cases.
AB  - Ingestion of foreign bodies occurs frequently in children, but there are no
      definite management guidelines. We reviewed 42 pediatric cases of accidental
      ingestion of foreign bodies with or without symptoms during the past 10 years. In
      decreasing order of frequency, the foreign bodies included: coins, sharp objects
      (needle, pin), bones (fish and chicken bone), metal object, food, seeds, plastic
      material, magnets, jewelry ring, and others. The majority of children were 5
      years old or younger. At the time of presentation, the vast majority of objects
      were located in the esophagus. Sixty percent of the patients had symptoms, such
      as abdominal pain, vomiting and cough. Management included observation,
      esophagoscopy, panendoscopy, and laparotomy. Four patients (9.5%) had
      complications. One patient who ingested a magnet suffered from esophageal
      perforation with mediastinitis. Two had deep neck abscess due to esophageal
      penetration by bones. Another patient had hemorrhagic gastritis after swallowing
      a coin. All patients discharged after treatment, and none died.

PMID- 14964982
TI  - Epidemiological and clinical features of group A Streptococcus pharyngitis in
      children.
AB  - In order to understand the prevalence of childhood streptococcal pharyngitis,
      isolation of group A Streptococcus (GAS) was attempted from throat swabs of
      pharyngitis patients. Children aged between 1 and 15 years presenting to the
      outpatient department with pharyngeal erythema were prospectively enrolled in the
      study. Demographic data and presenting symptoms and signs for each patient were
      recorded and a throat swab was taken. Of 1175 throat cultures obtained, GAS was
      isolated in 252 cases (21.4%). Of these, 142 (56.3%) were boys and 110 (43.7%)
      girls. A higher proportion of boys was found with GAS pharyngitis (1.29: 1). The
      mean age of GAS culture-positive patients was 7.8 +/- 2.3 years old. Patients
      aged between 6 and 11 years were more prevalent in GAS pharyngitis. Ninety
      (35.7%) of our GAS pharyngitis patients occurred between March and May. A second
      smaller peak occurred between October and December. The following factors showed
      independent positive correlation with GAS infection: sore throat (p < 0.001), no
      coryza (p = 0.011), tonsillar swelling (p < 0.001), anterior cervical adenopathy
      (p = 0.029) and scarlatiniform rash (p < 0.001). However, GAS was found in less
      than half of the patients who had these clinical manifestations. In conclusion,
      pharyngeal infection with GAS in children is not uncommon. The prevalence of GAS
      pharyngitis is related to patient gender, age, and month of the year. Diagnosis
      of GAS pharyngitis based on clinical features alone is unreliable.

PMID- 14964983
TI  - Continuous midazolam infusion in the treatment of uncontrollable neonatal
      seizures.
AB  - A prospective open-label study was designed to determine the efficacy and safety
      of continuous midazolam infusion in neonates with uncontrollable neonatal
      seizures. Patients whose seizures could not be controlled by diazepam, phenytoin
      or phenobarbital were enrolled. Midazolam was given as an intravenous bolus dose
      followed by continuous intravenous infusion. Thirty-two patients fulfilled the
      inclusion criteria. Midazolam terminated the seizures in all patients. The
      maximum dose of midazolam ranged from 1 microgram/kg/min to 15 micrograms/kg/min,
      with average of 4 micrograms/kg/min. Four patients had recurrent seizures, which
      stop after midazolam was reinstituted. There were no significant changes in serum
      sodium, potassium, calcium or glucose in any of the patients. Adverse effects
      included hypotension in 12 patients (38%) that was successfully controlled with
      intropic agents (dopamine and/or dobutamine) and transient urinary retention in
      12 (38%). Our study suggests that midazolam is safe and effective for the
      treatment of uncontrollable neonatal seizures.

PMID- 14964984
TI  - Liver abscess in children: a single institutional experience in southern Taiwan.
AB  - Liver abscess is uncommon in children. The purpose of this study is to evaluate
      the predisposing factors, pathogens, duration of hospitalization, and the
      managements of liver abscess in children. From 1986 to 2001, fifteen children
      were admitted to our hospital under the diagnosis of liver abscess. Thirteen
      cases were older than 8 years old and two were younger than one year old. Fever
      (15/15, 100%) and abdominal pain (13/15, 87%) were the most common symptoms.
      Twelve patients (80%) had prolonged fever (fever for 7 days or longer before
      diagnosis). Eleven (73%) cases were cryptogenic in origin. Most of the
      microorganisms were obtained solely from cultures of pus. Klebsiella pneumoniae
      was the most common organism isolated (6/15, 40%). Beside administration of
      antibiotics, percutaneous catheter drainage (PCD) was performed in 11 patients
      (73%); only one underwent surgical intervention due to poor response to PCD
      management. All of our patients were surviving after at least one year follow-up.
      In conclusion, liver abscess should be suspected in the patients with prolonged
      fever of unknown origin and abdominal pain. PCD combined with adequate
      antibiotics were sufficient for therapy of liver abscess in most cases. K.
      pneumoniae was the most common isolated pathogen in southern Taiwan.

PMID- 14964985
TI  - Surgical closure of patent ductus arteriosus in preterm infants at neonatal
      intensive care unit.
AB  - Between January 1997 and June 2002, we retrospectively reviewed the records of
      all premature infants (birth weight less than 2000 g) admitted to the newborn
      intensive care unit (NICU) at Chi Mei Medical Center. Among the 399 premature
      infants (birth weight less than 2000 g) surviving more than one week, 111 infants
      were diagnosed with patent ductus arteriosus (PDA). Seventeen premature infants
      underwent surgical closure of PDA after failure of indomethacin treatment. The
      indication for surgical closure of PDA was ventilator dependence and/or
      congestive heart failure in infants with echocardiographic evidence of a ductus
      arteriosus. The mean gestational age and birth weight were 26.9 +/- 2.4 weeks
      (range 23-32 weeks) and 978.8 +/- 360.1 g (range 494-1920 g), respectively. The
      mean age and weight at the time of operation were 28.1 +/- 12.4 days (range 13-61
      days) and 950.8 +/- 390.4 g (range 402-2120 g), respectively. All the operation
      procedures were performed in our NICU, using operating room personnel, thus
      eliminating the risks of patient transport. There was no intraoperative death.
      Three infants died in hospital due to other problems. One died of sepsis and the
      other two died due to bronchopulmonary dysplasia (BPD) and suspected sepsis.
      There were only two infants who had complications after surgical closure of PDA.
      One infant had left pneumothorax with subcutaneous emphysema and the other one
      had right upper lung collapse. We conclude that surgical closure of the PDA for
      the premature infant can be a safe and effective procedure performed in the NICU,
      when indomethacin closure is ineffective or contraindicated.

PMID- 14964986
TI  - Behcet's disease in childhood: report of one case.
AB  - We report on a 6 yr 7 m-old girl who had suffered from recurrent oral ulcers
      since July, 2000. Anal ulcers were also noted initially, and arthralgia was
      observed. Skin testing (pathergy test) showed only mild erythematous changes over
      the test area. HLA typing revealed HLA-B56. Intestinal symptoms included watery
      diarrhea with occasional blood. No ocular involvement was found. Her ailment was
      diagnosed as incomplete Behcet's disease with intestinal involvement. Diagnosis
      of Behcet's disease in childhood is a challenge and there are only a few studies
      on juvenile Behcet's disease (JBD) in the literature, with only a small number of
      patients. According to the literature, Behcet's disease in childhood is
      characterized by a low incidence of ocular lesion and a high incidence of
      intestinal involvement, as exhibited in this case.

PMID- 14964987
TI  - An outbreak of scombroid fish poisoning in a kindergarten.
AB  - We report an outbreak of scombroid poisoning at one kindergarten on September 25,
      1997. There were 94 cases. The onset of symptoms of scombrotoxin after ingestion
      of fish is rapid (40 to 50 minutes after consumption). Clinical manifestation
      consisted of hyperemia, particularly on the face and neck (94.7%), nausea and
      vomiting (17.0%), abdominal pain (17.0%), pruritus (4.3%), headache and dizziness
      (4.3%) and diarrhea (3.2%). The duration of symptoms was 3 hours on average. Most
      patients responded to antihistamine very well. The poisoning was caused by the
      ingestion of spoiled scombroid fish. The tissues of scombroid fish had undergone
      a number of changes provoked by bacteria and the uncooked fish containing 2,104
      ppm of histamine whereas cooked fish containing 1,980 ppm (198 mg/100 gm) of
      histamine was found in this accident.

PMID- 14964988
TI  - Congenital nephrotic syndrome: report of an infant with diffuse mesangial
      sclerosis.
AB  - A case of congenital nephrotic syndrome (CNS) caused by diffuse mesangial
      sclerosis (DMS) is presented. A female baby weighting 2,680 gm was delivered at
      35 weeks' gestation. She had early onset of generalized edema, heavy proteinuria,
      oligouria, uncorrectable hypoalbuminemia, and rapid progression to renal failure.
      Even after being treated with strong antibiotics (teicoplanin and ceftazidine),
      the infant died of septic shock with Enterobacter cloacea, only sensitive to
      imipenem, at the age of 7 days. The necropsy showed diffuse mesangial sclerosis.
      This case demonstrates that prematurity, low birth body weight and early onset of
      symptoms are not pathognomonic of the congenital nephrotic syndrome of the
      Finnish type (CNF). It can also occur in DMS. Besides, empirical antibiotics
      should be started promptly and should cover the major hospital strains of
      bacteria if the patient is not well.

PMID- 14964989
TI  - Neuronal intestinal dysplasia type B with massive small intestinal hemorrhage:
      report of one case.
AB  - Neuronal intestinal dysplasia type B is characterized by poor intestinal motility
      that usually results in constipation. Massive gastrointestinal hemorrhage is very
      unusual as the initial presentation in this disease entity. We report on a 3-year
      and-7-month-old boy who had experienced two episodes of life-threatening lower
      gastrointestinal hemorrhage and high fever. Technetium-99m labeled red blood cell
      scan and the Meckel's diverticulum scan failed to demonstrate the bleeding point.
      The results of panendoscopy and colonoscopy were negative. Laparotomy revealed a
      70 cm-long thick-walled intestine (from 100 cm to 170 cm below the Treitz
      ligament) with cord like material formed by mucosa debris, blood clot and mucus.
      Pathology report revealed hyperplastic nerve bundles in submucosal plexus with
      giant ganglion formation, consistent with neuronal intestinal dysplasia type B.

PMID- 14964990
TI  - Congenital esophageal duplication cyst: report of two cases.
AB  - Esophageal duplication cysts account for a small percentage of benign esophageal
      tumors and are frequently asymptomatic. Diagnosis is difficult, and patients
      often seek treatment when complications such as respiratory distress, bleeding,
      or infection develop. Surgical excision is recommended at the time of cyst
      discovery whether or not symptoms are present. We report 2 newborn cases with
      esophageal duplication cysts. Symptoms included respiratory distress and palpable
      neck mass. Computed tomography demonstrated cystic masses in the retropharyngeal
      space. Both patients underwent surgical resection of the cyst and the symptoms
      were relieved. Histopathologic examination revealed esophageal duplication cysts.

PMID- 14964991
TI  - Ovarian cyst with torsion presenting as a wandering mass in a newborn.
AB  - A case of ovarian serous cystadenoma with torsion presenting as a wandering
      abdominal mass is reported. A full-term baby girl was noted to have a left pelvic
      cyst by prenatal ultrasound at the 34th gestational week. After delivery, a
      series of work-ups, including ultrasonography and CT scan, revealed a cyst with
      fluid-debris level in the right pelvis. An ovarian cyst with torsion was
      suspected and surgical intervention was done when she was 7 days old. The
      operative findings confirmed a left ovarian cystic mass with torsion. A left
      salpingo-oophorectomy was performed smoothly. Pathology revealed the typical
      microscopic findings of ovarian serous cystadenoma, a benign epithelial tumor of
      ovary. We suggest that a wandering ovarian cystic mass in female fetus and
      newborn should be considered an indication for surgical intervention due to its
      high risk of torsion.

PMID- 14964992
TI  - Head and neck cancer care in Delaware: the advent of the Helen F. Graham Head and
      Neck Multi-Disciplinary Center.

PMID- 14964993
TI  - The social impact of medicine. Chapter 14.

PMID- 14964994
TI  - Medical meanderings.

PMID- 14964995
TI  - Domestic violence: how you can help.

PMID- 14964996
TI  - [State of intracardiac hemodynamics and features of left ventricular remodeling
      in patients with different types of diastolic filling of an ischemic origin].
AB  - 92 patients with stable forms of coronary heart disease (CHD) and different types
      of a diastolic filling have been investigated. Left and right ventricular volumes
      has been studied, the phase structure of the cardiac cycle on data obtained by
      means of echocardiography have been evaluated. The results show, that over the
      stages of progressing cardiac decompensation it has been noted left chambers of
      the heart being reconstructed as a uniform system. This process has a peculiarity
      in such patients as it proceeds irregularly causing systolic spherical
      enlargement of left ventricular, which is especially noticeable at the stage of
      forming abnormal heart muscle weakening and wane at the stage of developing
      restrictive type of a diastolic filling.

PMID- 14964997
TI  - [Circadian pattern features of paroxysmal atrial fibrillation in elderly patients
      with ischemic heart disease].
AB  - Forty-eight elderly patients with IHD and paroxysmal atrial fibrillation were
      studied to determine circadian pattern of arrhythmia onset. The data were
      obtained by detailed interview and analysis of medical documents. The found
      variations were fitted to cosinusoidal function with a period of 24 hours Y =
      9.75 + 3.5cos(2 pi t/24 + 0.2) (R2 = 0.69; F = 10.2; P < 0.01; two first
      coefficients of equation are significant by t-test, P < 0.01), the peak of
      arrhythmia onset was observed about midnight. 59.8% of overall number of episodes
      developed at dark period of day (P < 0.05). Findings testify that time periods of
      arrhythmia onset increase in number with disease evolution. It may be an
      additional criterion of paroxysmal atrial fibrillation transformation into its
      permanent form.

PMID- 14964998
TI  - [Profile of heart rate variation and diurnal rhythm of blood pressure change in
      patients with mild to moderate arterial hypertension].
AB  - The aim of this study was to estimate the heart rate variability and blood
      pressure in dipper and nondipper, mild to moderate hypertensive patients and
      evaluate the correlation of these data. 41 patients were included in this study.
      All patients underwent the bifunctional ambulatory blood pressure and ECG
      monitoring ("Cardiotens-01", Medithech, Hungary). The correlative analysis was
      done with the programme "Microsoft Excel". The dipper and nondipper patients with
      mild to moderate arterial hypertension were found not to have any significant
      differences in average heart rate variability patterns, but nondippers had more
      significant vegetative disorders, that was reflected in converse correlation
      between heart rate variability and blood pressure patterns. In dippers there was
      noted the direct correlation characterizing the activation of the compensatory
      mechanisms.

PMID- 14964999
TI  - [M. tuberculosis drug resistance and occurrence in patients with pulmonary
      tuberculosis].
AB  - The paper presents the results of M. tuberculosis drug resistance analysis. The
      material was phlegm obtained from 1060 patients treated during 1994-2001 y.y. The
      tendency of rising of M. tuberculosis drug resistance rate and polyresistance has
      been established. Unfortunately, a great deal of patients were undercovered with
      drug resistance M. tuberculosis which can massively grow on cultural medium with
      peak concentration of streptomycin, kanamycin, rifampicin and PAS(A), as stated
      above it necessitates to modernize the inspection system directed to determine M.
      tuberculosis drug resistance.

PMID- 14965000
TI  - [Clinical and topographic features of manifestations of cerebral vascular
      disorders in patients with vascular encephalopathy and cerebral arterial
      architecture anomalies].
AB  - The article presents the study of clinicotopographic features of the
      manifestations of cerebral disgemia in 129 patients with chronic cerebrovascular
      encephalopathy in the presence of abnormal cerebral arterioarchitectonics. It was
      completed by means of clinico-neurological and instrumental (MRI, MRA)
      investigations at the republican "Pheophania" clinic. Our data suggest that
      including MRI of brain with vascular mode into algorithm of investigation of
      patients with vascular encephalopathy to reveal and establish the degree of
      pathological changes is worthwhile as it will help to differentiate different
      kinds of cerebral affections, treat and evaluate a degree of risk of progressing
      a disease. Criteria for considerably early diagnostics of prognostically
      unfavourable forms of cerebrovascular insufficiency need further developing as at
      very this stage therapeutic actions are most effective.

PMID- 14965001
TI  - [Content of different cytokines in the blood of healthy children and their
      siblings who are either.positive or negative for diabetes-associated
      autoantibodies (GADA, 1A-2A, IAA)].
AB  - Content of different cytokines (IF alpha, TNF alpha, IL-1 alpha, IL-4, IL-6 and
      IL-10) was examined in the blood serum in two groups of healthy children-siblings
      with type 1 diabetes mellitus with and without revealed insulin autoantibodies
      against pancreatic islets (GADA, IA-2A and IAA) by enzyme-like immunosorbent
      assay (ELISA). In the group of patients with two and more revealed autoantibodies
      the higher indices in the number of IF alpha, TNF alpha and IL-6, and the
      decrease in the level of IL-4 comparing with the group of children with negative
      reaction to diabetes associated autoantibodies were more often observed.

PMID- 14965002
TI  - [Cervicitis and cervical intraepithelial neoplasia: cytomorphological and
      molecular biology analysis].
AB  - The actual research has shown that the important factor of CIN occurrence in the
      HPV presence is a chronic bacterial cervicitis. Another research of the HPV
      associations with other urogenital infections has shown that mycoplasma and
      papillomavirus associations are dominating and they occur twofold often in all of
      the examined women with cervical pathology in comparison with healthy persons.
      Inflammatory processes in cervix of the uterus should be related to factors of
      the increased risk of CIN development.

PMID- 14965003
TI  - [Dysplastic endometriosis as a separate nosological form].
AB  - The paper deals with analysis of pathogenesis features occurred in pathologically
      proliferative endometry (PPPE). Patient's state associated with PPPE is proposed
      to single out in a separate nosologic unit--dysplastic disease of endometry
      (DDE). Clinical and morphological classification of DDE is presented. DDE is
      regarded as the disease of an organism as in whole that suppose comprehensive
      approach to its diagnostics and treatment, forecasting further complications and
      carrying out adequate preventive measures. It assists in the improvement of
      diagnostic and treatment effectiveness of the disease, prevention of possible
      endometrium transformation in cancer.

PMID- 14965004
TI  - [Effectiveness of fecal elastase 1 in diagnosis of the external secretion of the
      pancreas].
AB  - The article presents results of the investigations of faecal elastase I level in
      patients with different diseases of the pancreas, at different stages of
      pancreatic insufficiency. On the basis of existing scientific data and own
      investigations the authors conclude, that determination of faecal elastase 1
      level is a high sensitive technique which might be regarded as a "gold" standard
      in diagnostics of pancreas insufficiency.

PMID- 14965005
TI  - [Efficacy of anti-Helicobacter therapy in children with ulcer-like functional
      dyspepsia].
AB  - The article presents new results of treatment of 69 children with ulcer-like
      dyspepsia, associated with Helicobacter pylori. Triple therapy included Proton
      Pomp Inhibitor (PPI-omeprasol) and two antibiotics (amoxicilline and
      claritromicine). The obtained results have shown good effectiveness of the
      eradicating triple therapy in children with Helicobacter pylori-associated ulcer
      like dyspepsia.

PMID- 14965006
TI  - [Functional changes in the lower part of the urethra in women following
      hysterectomy and hysterectomy-ovariectomy ].
AB  - Functional deterioration of a lower part of the urethra has been observed in
      woman after the operation. It has been partially recovered at the late
      postoperative period. Further studying pre- and postoperative function of a lower
      part of the urethra is of importance to develop a strategy of prevention and
      treatment functional deterioration of a lower part of the urethra in woman after
      the operation of hyster- and hysterovaroactomia.

PMID- 14965007
TI  - [Features of clinical presentation of malignant adrenocortical tumor cortex
      metabolism over time].
AB  - Malignant adrenocortical tumors is serious oncological pathology, which without
      early diagnosis and radical, first of all, surgical treatment leads to death. The
      authors have analyzed the treatment results of 216 patients with adrenocortical
      carcinomas, which were in clinic during 1968-2002. The tumors were 32.6% of all
      adrenal tumors. Most of the tumors were hormone-active. The best results were
      obtained with performing primary radical surgery at the early stages (without
      appearing of regional metastasis). The performing of reoperations in majority of
      cases guarantees the remission of disease, but seldom could be radical. The use
      of chloditan makes longer the survival level, but in the bulk of cases chloditan
      used as an additional curative method.

PMID- 14965008
TI  - [Differential diagnosis of giant cell tumors].
AB  - The article shows differential diagnosis of giant sell tumor of bone with bone
      cystae, displasia fibrosis, chondroblastoma, osteosarcoma, chondrosarcoma,
      plasmocitoma, enchondroma and bone metastases. The main methods of diagnosis is
      morphological investigation of biopsy material.

PMID- 14965009
TI  - [Total hip replacement in elderly and senile patients with initial femur neck
      fractures].
AB  - We carried out researches with the purpose of comparison of operative treatment
      results of femur neck fractures in elderly and senile patients with those in
      other countries. Total hip replacement technique was used over the period of 1991
      2002 yy. for 123 patients with femur neck fractures. We have used "Smith &
      Nephews" or "Zimmer" prostheses with "Polacos" or "Osteobond" acrylcements.
      Surgical approach tactics is very important for prophylaxis of early and late
      postoperative complications. Active and of sound mind patients with femur neck
      fractures should undergo total hip replacement procedure. Rehabilitation is also
      an important factor in preventive early and late postoperative complications.

PMID- 14965010
TI  - [Morphological characteristics of chronic toxic hepatitis treated with neoselen].
AB  - The purpose of the given research work was to study the features of morphologic
      changes arising during the treatment of chronic hepatitis with NEOSELEN. Chronic
      active hepatitis was set up in laboratory rats, post-forming in chronic
      persisting hepatitis and its transformation in a certain part of animals into
      cirrhosis by administration of HELIOTRINE over the period of 40 days.
      Morphologically hepatic cirrhosis was small nodular. NEOSELEN was found to have a
      good therapeutic effect in treatment of chronic hepatitis as we have seen
      noticeable remittance of destructive necrotic changes in hepatic parenchymatouse
      elements and reduction in a volume of proliferative inflammatory infiltration
      along with acceleration of fibrosis process only in periportal zones of hepatic
      lobules. The therapeutic efficacy of NEOSELEN prevents transmission of chronic
      hepatitis into cirrhosis in a greater part of animals thus giving morphologic
      signs of importance of NEOSELEN in a restorative process of destructive and
      inflammatory changes in the affected liver.

PMID- 14965011
TI  - [Efficacy of omeprazole in the treatment of Helicobacter pylori-associated
      duodenal ulcers... in children].
AB  - We have observed 25 children: 15 (60%) girls, 10 (40%) boys in age of 11 to 15
      y.o. with duodenum ulcer disease. 19 children were found having genealogical
      ulcer disease. The duration of the disease in the children varied from 6 months
      to 6 years. The children with long term ulcer disease anamneses have the disease
      relapse as often as every 4-6 months, 3 children were found with complications of
      the disease. All children were prescribed omeprazolum along with antibiotics
      (amoxicillinum, metranidasolum). Omeprazolum was prescribed in doses: 20 mg 2
      times per day over 7 days, after it 20 mg 1 time per day over 1 week. The above
      mentioned therapy showed good results, ulcer craters have been epithelized in
      more than a half of the children, in 68% of patients over 14 days. Using of this
      therapy positively affects the inflammatory and structural changes of gastric
      mucous coat and the acid level.

PMID- 14965012
TI  - [Experience in the application of pramistar, a new nootropic preparation, in the
      treatment of memory disorders in patients with cerebrovascular pathology].
AB  - Morbidity rise of cerebrovascular pathology is followed by remarkable cognitive
      decline. Chronic cerebral blood insufficiency and stroke consequences compose a
      group of the diseases which lead to different types of memory deterioration,
      consecutive memory decline and as a result to professional and social
      dysadaptation. The morphological basis of the problem consists in progressive
      structural cerebral deficit with forming a new adaptive system. The activity of
      this system is often not effective due to a lack of mediator supply. We have
      investigated the effects of monotherapy by a new nootropic drug--pramiracetam
      (Pramistar) on neuropsychological symptoms of memory deterioration in patients
      with chronic cerebrovascular insufficiency and stroke consequences in basilar and
      carotid vascular basin. The data obtained suggest statistically significant
      heterogeneous influence of the medicine on intensity of the evaluated symptoms.

PMID- 14965013
TI  - [Vestibular disorders and methods for their correction].
AB  - The analysis of etiological agents and clinical presentations of vestibular
      disorders was presented in the article. Pathogenetic way of treatment of
      vestibular disorders is substantiated by the author. The paper gives data
      obtained which show Betaserk treatment efficacy.

PMID- 14965014
TI  - [Occupational standing vibration rate and vibrational diseases].
AB  - Occupational standing vibration rate is proposed in evaluating a degree of
      impairment of an organism activity. It will allow more widely to introduce
      specification of quality and quantity in assessment of the development of
      vibrational disease. According out-patient and inpatient obtained data we have
      established criterial values of functional changes in accordance with accumulated
      occupational standing vibration rate. The nomogram was worked out for defining a
      risk of the development of vibrational disease in mine workers. This nomogram
      more objectively can help in diagnostics of the disease.

PMID- 14965015
TI  - [Evaluation of individual predisposition to development of musculoskeletal system
      diseases].
AB  - A technique was worked out on the basis of studying of physiological indices of
      the main and medical aid appealability concerning musculoskeletal system diseases
      (MSD), physical examination of workers. It will allow for certain determine the
      character of individual predisposition to the development of the disease and in
      84% of the cases rather sooner predict the disease if a worker has high
      individual predisposition and in 55.2% of other cases. Combination of tension and
      pain sensitivity indices measuring up 21-80 and 1.1 mm and more; 81-160 and 1.0
      mm and more; 161-220 and 0.9 mm and more; 221-300 and 0.8 mm and more; 301 and
      more, 0.7 mm and more accordingly characterize high individual predisposition;
      less 50 and 0.5 mm--tolerance to the disease. A risk of the development of
      musculoskeletal system diseases conditioned by individual predisposition from the
      mathematical analysis happened in 16.2%. Application of the method before
      receiving the job can both reveal individual predisposition to musculoskeletal
      system diseases and prevent from harmful industrial conditions. It will decrease
      a risk of the development of MSD, keep sound health and prolong professional
      activity.

PMID- 14965016
TI  - [Functional dyskinesis of bile excretory ducts: clinical significance and its
      correction].
AB  - Our study has shown the clinical significance of treating of a gall-bladder
      hypomotor dyskinesia and hypertone of the Oddi's sphincter. Hypomotor dysfunction
      of gall bladder occurs in 24% patients with cholelithiasis and after a remote
      lithotripsy in 62.5%, 50% of patients with stenosis of Oddi's sphincter have
      microcholelithiasis (MCL) and 100% of patients have "sludge".

PMID- 14965017
TI  - [Gastroesophageal reflux disease as a surgical problem].
AB  - Photodynamical and chromoesophagoscopic diagnostics in recognizing of Barrett
      disease are described in the article. The indications for surgical treatment of
      esophagogastric reflux disease are presented.

PMID- 14965018
TI  - [Peptic ulcer in women: personal characteristics and types of attitude to the
      disease].
AB  - We have studied various types of the personal attitude to the disease in 48 women
      with the peptic ulcer. The ergopathologic type is dominant in all women. Besides
      that, women of 40-49 y.o. are neurotic and anxious types. Women of 50-59 y.o. are
      neurotic type too, but not euphoric. Therapeutic tactic should consider the
      personality reactions to the disease.

PMID- 14965019
TI  - [Organizational approach to diagnostics and treatment of illnesses of the
      digestive organs].
AB  - The work reflects the organizational approach to prevent the continuing loss of
      work capacity in the patients with digestives problems. The positive effect from
      introduction of the uniform standards of diagnostics and treatment, in
      particular, body of keeping operations is emphasized at complications of a
      stomach and duodenal ulcer disease.

PMID- 14965020
TI  - [Operative intervention as a factor provoking the ulcer formation process in
      patients suffering from chronic gastritis type B].
AB  - The article presents 27 cases of ulcer formation in the duodenal bulb that
      occurred in 8.3 +/- 0.13 days after an operative intervention carried out because
      of the calculous cholecystitis and coccygeal cyst. The chronic gastritis type B
      has been detected in all the patients in 100% of cases.

PMID- 14965021
TI  - [Endonasal electrophoresis of dalargin in the therapy of multiple and giant
      duodenal ulcers].
AB  - The paper presents the results of comprehensive examination and treatment of 120
      patients with giant and multiple duodenal ulcers at the N. A. Semashko Regional
      Hospital gastroenterological department. Was suggested, that combined therapy of
      patients with dalargine was most effective, then traditional therapy of peptic
      ulcer.

PMID- 14965022
TI  - [Efficacy of controloc in the treatment of acid-dependent diseases].
AB  - The results of treatment of duodenal ulcers and gastroesophageal reflux disease
      with using of modern proton pump inhibitor controloc (pantoprazole) are presented
      in this article. The positive influence of controloc on clinical course of the
      disease is found.

PMID- 14965023
TI  - [Changes in tissue viability of digestive organs in current surgical pathology].
AB  - Modern surgical treatment of people according with legislation and health care
      law has to consider defining of tissue viability. The paper deals with the
      technique directed to evaluate specific tissue viability by structure functional
      alterations indices of mitochondrion crista. The technique can be introduced into
      clinic practice for above mentioned purposes.

PMID- 14965024
TI  - Profiles in leadership. Liability reform ... for physicians, it's the issue.
      David Selby, MD.

PMID- 14965025
TI  - Wegener's granulomatosis in a pediatric patient.
AB  - Wegener's Granulomatosis (WG) is characterized by the clinical triad of upper and
      lower respiratory disease, and renal insufficiency. Because WG masquerades as a
      syndrome, its diagnosis is often delayed. Astute clinicians should include WG in
      their differential diagnosis when a patient presents with these classic findings.
      The diagnosis is a clinicopathologic one made by biopsy of appropriate tissue
      showing necrotizing granulomatous vasculitis. Lung tissue obtained by open
      thoracotomy has the highest diagnostic yield. At one time a universally fatal
      illness, WG is now treatable with cyclophosphamide and prednisone therapy with
      remission in most cases. The authors present a case report of a pediatric patient
      who was eventually diagnosed with WG. The case serves as a reminder to all
      clinicians to keep this entity as a part of their diagnostic armamentarium.

PMID- 14965026
TI  - From risky behaviors to chronic outcomes: current status and Healthy People 2010
      goals for American Indians in Oklahoma.
AB  - OBJECTIVES: The objective was to estimate the rates of behavior-related risk
      factors among American Indians in Oklahoma, and compare those to the Oklahoma
      general population rates and Healthy People 2010 goals where available. METHODS:
      The REACH 2010 Native American Behavioral Risk Factor Survey, a random telephone
      survey, was conducted in 2000 as a part of the larger national REACH initiative.
      It had 3,732 respondents and it included measures related to health status,
      health care access, overweight, exercise, tobacco use, alcohol use, hypertension,
      cholesterol screening and diabetes. RESULTS: Self-reported health status was
      excellent or very good among 52% of respondents and fair or poor among 21%. Sixty
      one percent of adults were overweight or obese. Prevalence of current cigarette
      smoking was at 33%. Binge drinking in the last month was present among 18% of
      American Indian adults. Thirty percent of adults did not engage in any leisure
      time physical activity during the last month. Diagnosed high blood pressure was
      reported by 26% of respondents, and prevalence of diabetes exceeded 8%.
      CONCLUSIONS: Majority of the recorded behaviors are above Healthy People 2010
      goals, and exceed Oklahoma general population rates. There are also some
      significant gender differences, demonstrating the need for targeted intervention
      activities.

PMID- 14965027
TI  - Patient page #44. Quit tips. Don't let another year go up in smoke.

PMID- 14965028
TI  - Terrorism symposium update and conclusion.

PMID- 14965029
TI  - Terrorism.

PMID- 14965030
TI  - Oklahoma medical board history: Part II.

PMID- 14965031
TI  - A year in review--legal developments and trends.

PMID- 14965032
TI  - [Effect of neuroendocrine cell differentiation of the human prostatic neoplasm
      cell line LNCaP on the characteristics of volume-sensitive chloride content].
AB  - By means of patch-clamp technique we examined changes in volume-regulated
      chloride current (ICl,swell) at neuroendocrine differentiation of androgen
      dependent LNCaP prostate cancer cells. In those cells with neuroendocrine
      differentiation resulted from an increase in the intracellular cAMP, ICl,swell
      became much faster in response to applying external hypotonic solution and cell
      swelling. Changes in final rectification and voltage-dependent inactivation were
      not detected, as compared to the control cells. The differentiation also
      diminished ICl,swell blockade by Ca2+ transported via store-operated channels
      (SOC). On the base of our data we suggest that potentiation of the current at
      neuroendocrine differentiation, at least in part, resulted from a decrease in an
      inhibitory effect of Ca2+, transported into a cell through SOC, on volume
      sensitive chloride current. Accelerated current in those cells might be induced
      by cytoskeleton rearrangement at the neuron-like growth.

PMID- 14965033
TI  - [Cardioprotective effect of heme oxygenase-1 induction by hemin on the isolated
      rat heart during ischemia--reperfusion].
AB  - The aim of the study was to determine the role of both an inducible isoform of
      heme oxygenase (HO-1) and products of heme catabolism (carbon monoxide (CO),
      cardiac bilirubin and Fe2+) in protecting myocardium against post-ischemic
      myocardial dysfunction. Rat hearts were isolated and perfused according to the
      Langendorff technique to evaluate the recovery of myocardial function after total
      ischemia (20 min) and reperfusion (40 min) and production of reactive oxygen
      forms at a reperfusion phase. Ischemia/reperfusion caused impairment in
      myocardial function: left ventricular developing pressure (LVDP) was shown to be
      decreased, while end-diastolic pressure (EDP) and both coronary perfusion
      pressure and coronary resistance increased. Free oxygen radicals were generated
      at the reperfusion phase which led to injuries to cardiomyocytes and creatine
      kinase efflux into perfusate. We have found that upregulation of HO-1 by
      preliminary (24 h before ischemia) injections of 25 mg/kg hemin (i.p.) resulted
      in improving the myocardial function due to increasing the enzyme activity and
      forming the cardial bilirubine, while generation of reactive oxygen forms was
      inhibited, as well as the contents of creatine kinase reduced. As a result,
      impairment in cardiomyocytes diminished, and coronary vessels dilated to improve
      the functional parametres of the heart work.

PMID- 14965034
TI  - [ATP-sensitive potassium channels and changes in their functional activity during
      streptozocin-induced diabetes mellitus].
AB  - Attenuation in the vasodilatory effects of a new synthesized opener of ATP
      sensitive K' channels on isolated aorta strips of rat has been shown under
      experimental (streptozocin-induced) diabetes mellitus. The level of that
      attenuation depended on the nature of initial vasoconstriction. The most
      pronounced decrease--43.34% as compared to the control responses in healthy rats,
      we observed after norepinephrine-induced vasoconstriction. Following preliminary
      angiothensin-induced vasoconstriction and potassium depolarization, attenuation
      in vasoconstriction was 20.37% and 22.4%, respectively. Norepinephrine inhibited
      vasodilator effects of phlocalin in the aorta of diabetic rats much more
      significantly, as compared to those after potassium depolarization. Inhibitory
      effects of angiothensin II in rats with diabetes mellitus did not differ from
      those in the control rats. At the same time, constrictory responses to biological
      active agents were preserved and they did not differ from those in control rats.
      We suggest that impairment in vascular reactivity under diabetes mellitus, at
      least in part, depends on the changes in the functioning of ATP-sensitive
      potassium channels.

PMID- 14965035
TI  - [Effect of inhibiting protein kinase C on calcium sensitivity of contractile
      apparatus of vascular smooth muscle during vasospasms of different origins].
AB  - The aim of the study was to investigate the role of protein kinase C (PKC) in
      changes in myofilament Ca(2+)-sensitivity of vascular smooth muscle cells (SMC)
      in rats at different vasospastic states: hypoxic pulmonary vasoconstriction,
      genetically determined hypertension, and hypertension resulted from ionizing
      radiation. All vasospastic states demonstrated rightward shifts in pCa-tension
      curves suggesting that myofilament Ca(2+)-sensitivity had increased. In
      chemically (beta-escin) skinned pulmonary artery, hypoxia-induced increase in
      myofilament Ca(2+)-sensitivity was completely abolished by PKC inhibitor
      chelerythrine. The similar results were demonstrated in skinned aorta SMC of
      spontaneously hypertensive rats where an increase in myofilament Ca(2+)
      sensitivity was also abolished by PKC inhibitors chelerythrine and staurosporine.
      The chelerythrine partially inhibited myofilament Ca(2+)-sensitivity that had
      increased following gamma-radiation. The data suggest the key role of PKC
      activity in modulation of myofilament Ca(2+)-sensitivity in SMC. We conclude that
      PKC-mediated increase in myofilament Ca(2+)-sensitivity is one of the main
      mechanisms which contribute to the vasospasm of different genesis.

PMID- 14965036
TI  - [Renal mechanisms of protective potassium effect in essential hypertension].
AB  - In experiments on nonlinear rats, the renal functions were investigated at
      aqueous diuresis induced by intragastric administration of sodium potassium,
      potassium hydrocarbonate (20 mM/kg), and potassium succinate (10 mM/kg). We have
      found that the load by potassium raised glomerular filtration rate and sharply
      increased excretion of not only K+ but also Na+ and Cl- with urine, that led to
      hyponatremia and hypochloremia following hyperkalemia. In addition, the
      intracellular concentration of K+ increased more than extracellular one,
      especially after administrating KHCO3 and potassium succinate. It promoted
      potassium efflux from cells by concentration gradient, hyperpolarization of
      cellular membrane and vascular smooth muscle relaxation. Thus, these data explain
      renal mechanisms of a known protective effect of potassium at essential
      hypertension.

PMID- 14965037
TI  - [Effect of thymostimulin on endocrine thymus function in thyroidectomized rats
      during suppressive hormone therapy].
AB  - Due to disorders of hormonal balance in the organism, a decrease in thymic
      endocrine function occurred in rats after thyroidectomy. After removing the
      thyroid gland, we observed 1,3-2,2-fold decrease in the level of thymic hormone
      thymulin in the blood serum. When thyroxin was applied at a suppressive dose,
      endocrine function of the thymus did not restore. Injections of thymostimulin
      (Tp1) or its combination with thyroxin to thyroidectomized animals restored the
      level of thymulin up to the level in the intact rats due to effects of either
      injected preparation or induction of substances possessing thymosine-like
      activity.

PMID- 14965038
TI  - [Age-related changes in fatty acid composition of the erythrocyte membrane].
AB  - Taking into account the prerequisites existing in elderly people for disturbances
      in metabolism of polyunsaturated fatty acids (PUFA) which are risk factors of
      cardiovascular pathology, we studied the content of separate fractions of fatty
      acids (FA) in erythrocyte membrane of practically healthy people aged over 60.
      Seventeen practically healthy subjects aged 60-74 were investigated. All of them
      have been under long-term observation at the Institute of gerontology, AMS of
      Ukraine. A thorough preliminary examination proved them to be free from any
      pathology which might affect the results of studying the lipid composition of
      erythrocyte membrane. Twenty healthy subjects aged 20-29 served as controls. The
      fractions of FA as well as HDL and LDL were determined in erythrocyte membrane.
      In elderly healthy people the results obtained have shown a statistically
      significant decrease in the content of unsaturated FA and PUFA in erythrocyte
      membrane. The level of PUSFA decreased due to both omega-6 and omega-3 fractions
      as well as at the expense of their precursors. However, the decrease in the level
      of omega-3 fraction was more pronounced. As evidenced by a decrease in the
      content of unsaturated FA and PUFA in lipoproteins of both high and low density,
      the disturbance of PUFA transport by lipoproteins is one of the mechanisms of the
      decrease in PUFA level in the erythrocyte membrane.

PMID- 14965039
TI  - [Effect of pH on ATPase myosin activity of different muscle types].
AB  - The influence of pH in the medium on ATPase myosin activity in different muscle
      types was investigated. It has been found that myosin ATPase had two maxima with
      different values of the specific activity in cardiac, skeletal and smooth muscles
      depending on pH, namely: 6.0-6.5 and 9.0-9.5. The dependence of physiological
      properties of different muscle types on the physical-chemical and structural
      peculiarities of myosin has being discussed.

PMID- 14965040
TI  - [Mechanisms of inhibiting thymus endocrine function in tumor growth].
AB  - The experiments were conducted on a model of intraorganic growth of Geren
      carcinoma (GC) in spleen of non-linear mice. It has been shown that titer of
      thymic serum activity (TSA) decreased sharply in the blood at a stage of settling
      transplants down (7th day), while the level of an inhibitor for thymic serum
      factor (FTS) increased in a statistically significant way. At progressive tumor
      growth, the level of TSA in the circulation raised a little on the 10th day but
      it was still reduced in comparison with that before inoculation of GC. Traces of
      the inhibitor for FTS were detected only in 18 and 25 days of tumor growth. We
      have found resemblance between these substances and those in low-molecular
      extracts of lymphocytes (LEL). The LEL from cells of the spleen and the thymus of
      intact rats contained TSA and FTS inhibitor, both of T-cell origin, in ratio 1:1.
      Production of TCA and the FTS inhibitor was peculiar to immature cortisone
      sensitive T-lymphocytes. Anti-FTS serum in vitro completely neutralized TSA in
      both the blood and an extract of thymocytes but it effected neither the contents
      of TSA in the LEL of the spleen nor the level of FTS inhibitor in all the samples
      investigated. The data received testify to an important role of FTS inhibitor in
      the pathogenesis of tumor progression.

PMID- 14965041
TI  - [Relationship between hypercholesteremia and morphological changes in the aorta
      and kidney].
AB  - Effects of exogenic and endogenic hypercholesterinemia on morphological structure
      of aorta and liver were investigated. Both exogenic and endogenic
      hypercholesterinemia have been shown to induce different morphological changes in
      tissues of the aorta and the liver which were more expressed at endogenic
      hypercholesterinemia, as compared to exogenic one. The data obtained suggest that
      more pronounced impairments in the tissues examined which led to endogenic
      hypercholesterinemia were the result of a great number of neuroendocrine
      mechanisms involved in a stressful reaction.

PMID- 14965042
TI  - [Metabolic changes in salivary glands with concurrent stomach ulcer and their
      correction by L-arginine].
AB  - On the model of peptic ulcer the mechanisms of interrelations between salivary
      glands and stomach have been proved. Activation of proteolysis which took place
      together with a decrease in the activity of alpha 1--inhibitor for proteases in
      lipid peroxidation (LPO), and an increase in depolymerization of glycoproteins
      contributed much to that pathology. The most pronounced metabolic changes in the
      tissues of the salivary glands were observed in stress resistant animals. The
      preliminary administration of NO donor L-arginin prevented an activation of
      proteolysis and LPO intensity. It attenuated the pathogenic influence of the
      factors which induced the metabolic changes in salivary glands at peptic ulcer of
      the stomach.

PMID- 14965043
TI  - [Effect of systemic changes in microcirculation on the development of premature
      skin involution].
AB  - We studied the peculiarities of systemic microcirculation (bulbar conjuctiva) and
      effects of its changes on morphofunctional state of skin in women with premature
      skin involution. Impairments in both arterial and venous parts of
      microcirculation have been proved to be pronounced. Those changes were concluded
      to cause individual peculiarities of premature skin involution.

PMID- 14965044
TI  - [Bile acids in the process of canalicular bile formation].
AB  - This review summarizes the current knowledge of the role of bile acid in the
      canalicular bile secretion: its membrane transport in hepatocyte; molecular
      mechanisms and pathways of its regulatory effects on membrane transporters; the
      role of its hydrophobicity in membrane transporter regulation; hepatocyte
      necrosis and apoptosis at cholestasis induced by hydrophobic bile acids; the
      possible mechanisms of protective effects of ursodeoxycholic acid in cholestatic
      impairment of the liver.

PMID- 14965045
TI  - [Functional and structural characteristics of the nephron segments].
AB  - The review presents a modern view on the functional--morphological peculiarities
      of 12 segments of the nephron canaliculi possessing some functional, biochemical
      and histologic distinctions that should be taken into account to study
      physiology, biochemistry, morphology and pathophysiology of the kidney.

PMID- 14965046
TI  - [The Institute of Physiology of the National Academy of Sciences of Byelarus--50
      years].

PMID- 14965047
TI  - [A half-century in the field of preventive medicine and ecology. To the jubilee
      of I. M. Trachtenberg].

PMID- 14965048
TI  - [Mechanisms of nitric oxide activity in cardiovascular system as a basis of
      pathogenetic therapy of related diseases].
AB  - General characteristics and mechanisms of effects of nitric oxide (NO) and its
      role in the development of pathology are reviewed. Presented are the data about
      NO participation in the regulation of circulation and cardiovascular system; NO
      dependent mechanism of regulation of cardiovascular reactivity against the
      background of dysfunction of endothelium; cGMP-independent mechanism of NO effect
      upon Ca homeostasis and the sensitivity of myofibrils of smooth muscle cells to
      Ca ions; pharmacological correction of disturbances of NO metabolism and related
      endothelial dysfunction; role of age changes of the endothelial function in the
      development of cardiovascular pathology.

PMID- 14965049
TI  - [Effect of inhibitors of sodium-calcium exchangers on acetylcholine-induced
      hyperpolarization of endothelial cells in rat aorta].
AB  - The effect of selective sodium-calcium exchanger blockers on acetylcholine
      induced hyperpolarization of endothelial cells from excised rat aorta was
      investigated. Acetylcholine administration induced sustained endothelial
      hyperpolarization. In the presence of 100 microM benzamil, the blocker of forward
      and reversed mode of the exchanger, acetylcholine induced only short-lived
      hyperpolarization. When benzamil was introduced during the plateau phase of
      hyperpolarization the amplitude of hyperpolarization significantly and reversibly
      decreased. KB-R7943 (20 microM), the blocker of reversed sodium-calcium
      exchanger, exerted the similar effect. Benzamil-mediated inhibition of sustained
      hyperpolarization was observed when recordings were commenced from isolated
      endothelium. The results obtained suggest that reversed mode of sodium-calcium
      exchanger is activated in intact endothelial cells following stimulation by
      acetylcholine.

PMID- 14965050
TI  - [Age dependent dynamics of the critical points of physical exercise in healthy
      men].
AB  - Age dynamics of the critical points of an exercise in 240 apparently healthy men
      aged 18-95 years was investigated. It is shown that linear decrease of a level of
      critical load capacity, maximum oxygen consumption, thresholds of anaerobic
      exchange and decompensated metabolic acidosis takes place in aged individuals.
      The equations of linear regression of changes in these parameters with age are
      presented. Using the method of factor analysis it is demonstrated that in healthy
      men variability of critical points of physical activity is age-dependent. Age
      factor determines 58% of maximum oxygen consumption variability, 62% of
      decompensated metabolic acidosis variability and 51% of anaerobic exchange
      variability. At the same time 23% of maximum oxygen consumption variability, 26%
      of threshold of decompensated metabolic acidosis variability and 33% of threshold
      of anaerobic exchange variability depends on physical activity level.

PMID- 14965051
TI  - [Effect of enalapril on the blood lipid spectrum and on the calcium level in the
      aorta and liver during stress].
AB  - Possible mechanisms of influence of the angiotensinconverting enzyme in the
      calcigistia dynamics in the aorta and liver and lipid spectrum of the rat blood
      upon the long-live stress exposure were investigated. It is shown, that the
      blockade of the angiotensinconverting enzyme leads to the one-type changes of the
      calcium contents in organs studied, but with different quantity indicators. The
      contents of general cholesterol and high-density lipoproteins is intimately
      connected with the calcium contents in liver. Apparently, the results obtained
      mirror the most optimal mode of the cell survival in a long-term stress
      conditions, which are directly connected to a calcium homeostasis and its support
      by extra- and intracellular reserves.

PMID- 14965052
TI  - [Effect of sulfur dioxide on surface activity of the pulmonary surfactants and
      ultrastructure of type II alveolocytes].
AB  - Condition of the surfactant lungs system under sulfur dioxide action in
      concentration of 0.05 mg/m3 and 0.5 mg/m3 was studied in dynamics (1 hour, 24
      hours, 7 days) during the investigation of 108 white rat-males with the help of
      electronic-microscopic and physic methods. We established that sulfur dioxide
      decreases the surface activity of the lungs surfactant, damages the
      ultrastructure of II type of alveolocytes. The greatest changes of the surfactant
      lung system were induced by inhalation of sulfur dioxide in concentration of 0.5
      mg/m3.

PMID- 14965053
TI  - [Effect of polymer material thermal destruction products on external respiration
      and acid-base status of blood].
AB  - In experiments on white laboratory rats the influence of fluor-, cyan- and sulfur
      containing gaseous products, formed under thermodestruction of synthetic
      materials in normal and high environmental temperature on external respiration
      and some parameters of acid-base blood values was investigated. It was shown,
      that external respiration, due to considerable it depression, could not
      compensate neither hypoxic state, accompanied by hypoxemia, nor hypercapnia and
      acidosis, developed under the influence of toxic agents both in normal
      environmental temperature and in hyperthermia.

PMID- 14965054
TI  - [Using electromagnetic irradiation of extra high frequency for the correction of
      desynchronisation].
AB  - The infradian rhythmicity of the open-field behavior of rats under the influence
      of EHF-waves was investigated. It was shown the development of desynchronosis
      under the influence of EHF-waves on intact rats. Under the influence of EHF-waves
      the development of desynchronosis on hypokinesic rats was remarkable decreased.
      It was found that EHF-waves are able to modify the temporary organization of
      physiological systems, however, the magnitude and the character of these changes
      depend on functional state of the organism. It has been suggested that the
      ability of EHF-waves to modify temporary organization of physiological systems
      plays an important role in mechanisms of their biological action.

PMID- 14965055
TI  - [Characteristics of autonomic regulations in miners working in hard conditions of
      coal mines].
AB  - 72 miners aged from 30 till 40 years have been surveyed. It was established that
      to achieve socially acceptable results the miners use corresponding strategy
      doing their job. Under the influence of the work the functional states mediated
      not only by conditions of working environment but also by resistivity of the
      organism are developed. It is shown that highly productive, reliable and
      effective work is possible under adequate interactions of central and autonomic
      mechanisms of regulation. Alteration in these interactions, particularly, non
      adequate centralization of management processes decreases physical capacity for
      work. Enhancement of sympathetic effects on periphery that leads to development
      of hypertensive reactions has been observed. Such alterations are accompanied by
      an increase in physiological cost of work and decreased productivity of labor.

PMID- 14965056
TI  - [Effect of coherent and noncoherent laser irradiation on the cardiovascular
      system].
AB  - It has been shown that coherent and non-coherent laser emission oriented on
      rabbit eye affects vascular and cardiac components of haemodynamics while not
      shifting significantly the level of dynamic pressure. It is demonstrated that
      haemodynamic reactions are different upon long-term exposure of coherent and non
      coherent laser emission.

PMID- 14965057
TI  - [Sensorimotor reactions in students of high school age during different types of
      the weather].
AB  - The neuro-dynamical characteristics of the higher nervous activity of senior
      pupils in different weather types were investigated. The group of practically
      healthy pupils was given tests on investigation of the speed of the simple
      sensomotorical reaction (SSR), sigma of the simple sensomotorical reaction
      (Sigma), the medial speed of the choice reaction (CR), the speed of the choice
      reaction for the right (CRR) and the left (CRL) hand. The study was conducted on
      the days with favorable, conditionally favorable and unfavorable medical
      meteorological conditions. The results of the study of the neuro-dynamical
      characteristics of the higher nervous activity of senior pupils give the
      possibility to make a conclusion that they decrease as the weather conditions
      become worse. Senior school age is characterized by the improvement of the neuro
      dynamical characteristics of the higher nervous activity. The girls of the senior
      school age have shown higher results in different weather types than the boys.

PMID- 14965058
TI  - [The state of the glial intermediate filaments and learning in rats with
      experimental diabetes].
AB  - The effect of streptozotocin-induced diabetes on glial intermediate filament and
      behavioral reactions of rats was investigated. The water Morris test shows
      cognitive deficit in diabetic rats. The results of an immunoblot show both an
      increase in GFAP degradation and an increase in common GFAP amount in the brain
      of diabetic rats. The observations presented here suggest that diabetes induces
      the changes in activity of GFAP-positive glial cells. Such glial cells may be
      considered a key element in plasticity of nervous system. These results suggest
      that the impairment of learning and memory is accompanied by glial cytoskeletal
      reconstruction.

PMID- 14965059
TI  - [European code against cancer. Third revision (2003): advancing in cancer
      prevention].

PMID- 14965060
TI  - [Evaluation of the implementation of the FAPACAN programme to prevent cancer
      behavioral risk in primary care users in the North of Spain].
AB  - BACKGROUND: The evaluation of the process is an essential condition to correctly
      measure the impact of educational interventions on behaviour, its psychosocial
      determinants and the state of change, in the context of health promotion. The aim
      was to evaluate the quality of the implementation of the FAPACAN Programme,
      designed to prevent behavioural risk of cancer in Primary Care, and to improve
      its psychosocial determinants in the A.S.E. Model and the state of change
      according to Prochaska and DiClemente Theory. METHODS: The quality of
      implementation was measured by means of a visit to the health centre, by filling
      in a checklist 'in situ', and a phone survey with the patient. Centralisation and
      association measures were found (Pearson and Spearman's coefficient). A multiple
      regression model was obtained with the score made by the patient (range of 0 to
      8) and the covariables: gender, age, level of education, locality and family
      history of cancer. RESULTS: The quality scores obtained oscillate between 72% and
      81% of optimum quality. Significant differences were found owing to the
      administrator (better with fewer years of exercise) and the patient (better with
      higher level of study). CONCLUSIONS: In general, the quality of implementation
      was more than sufficient, in spite of the poor provision by the health system.

PMID- 14965061
TI  - [Intention of purchasing generic prescription drugs on the part of consumers in
      Asturias, Spain].
AB  - BACKGROUND: Ascertaining how consumers perceive the risk related to the use of
      generic prescription drugs and those factors which have the greatest impact on
      the intention to request a generic drug from the prescribing physician and/or the
      pharmacist for the purpose of determining any possible barriers or hindrances to
      the acceptance of generics and to gather information to aid healthcare managers
      in their decision-making processes. METHODS: Study on prescription drug use
      revolving around the degree to which patients are willing to request an EFG. In
      this quantitative transversal study, a total of 542 individuals were individually
      surveyed upon exiting a healthcare center or pharmacy in Asturias. A scale for
      measuring the perceived risk involved in the purchase of a prescription drug
      including 15 attributes grouped into five aspects was included in the
      questionnaire. Information was also gathered regarding the intention of using
      generic prescription drugs and on the demographic and socioeconomic
      characteristics of those surveyed. For the analysis of the results, a factorial
      confirmational analysis, multiple regression and univariate analysis were used.
      The data was processed using the EQS and SPSS statistics programs. RESULTS: Mean
      perception of the risk (scales 1-7): functional: 2.75; physical: 2.68: financial:
      2.19; psychological: 1.99; social: 1.42. Factors having a bearing on the
      intention of requesting generic prescription drugs from their physician:
      psychological risk (p = 0.000). On requesting the same from their pharmacist:
      psychological risk (p = 0.000) and social risk (p = 0.020). CONCLUSIONS: The
      agents interested in the development on the EFG market should target their
      communication efforts on putting the functional and financial aspects of the
      manufacturer's specialties and generic specialties on the same level, but should
      not leave out psychological and social aspects of the consumers' purchasing
      behavior.

PMID- 14965062
TI  - [The use of the capture- recapture method in evaluating the epidemiological
      meningococcal disease monitoring system in Tenerife, Spain (1999-2000)].
AB  - BACKGROUND: Meningococcal Disease is mainly monitored passively on the Canary
      Islands, the regular Compulsory Disease Notification channels being used. The
      objective of this study includes describing the qualitative and quantitative
      aspects of this system and evaluating the exhaustiveness, by means of the capture
      recapture system, of three information sources. METHODS: This study covers the
      1999-2001 period in Tenerife. The information was gathered from three sources:
      the Compulsory Disease Notification System, the Microbiology Laboratories and the
      hospital Minimum Basic Data Set. The Evaluation Protocols of the Monitoring
      System of the Atlanta Centers of Disease Control and Prevention were used. A log
      linear model was used for estimating the number of cases. The calculations of the
      exhaustiveness and the 95% confidence intervals were done in the SPSS10
      statistics package. RESULTS: The system was found to have an 84.9% sensitivity,
      and an 80.4% positive predictive value. The delay in notification (timeliness)
      fell within the 0.5-13-day range, averaging 3 days. The system was found to have
      a 76.6% overall acceptability. The exhaustiveness value was 98.1%. CONCLUSIONS:
      This disease is being monitored well, with a degree of sensitivity which would be
      revealing of a good notification level, also confirmed by its exhaustiveness.
      Although the positive predictive value is high, this could be indicative of the
      expeditious starting of antibiotic treatment which would hinder microbiological
      confirmation. The system is timely, affording the possibility of measures being
      taken for fast intervention.

PMID- 14965063
TI  - [Diagnostics upon hospital release of immigrants in the city of Valencia, Spain
      (2001-2002)].
AB  - BACKGROUND: Immigration has increased remarkably in Spain over the past ten
      years. For theoretical reasons, the question has been raised as to whether this
      population may possibly be responsible for a rise in the incidence and/or
      transmission of infectious diseases. However, very few studies have been
      conducted regarding the diseases among this group which would afford the
      possibility of ascertaining the importance of this statement. This study is aimed
      at quantifying the hospital care provided to this population in the city of
      Valencia. METHODS: The hospital release records were obtained from the Admissions
      Departments of the public hospitals in the city of Valencia. A one-year
      retrospective observational study was conducted throughout the October 1, 2001
      September 30, 2002 period. RESULTS: We retrieved 8,444 hospital admissions
      identifying 1,577 hospital admissions of immigrants. Similar percentages of
      immigrants recorded with their documentation in proper order (841; 51.16%) and
      immigrants supposedly undocumented (803; 48.84%) were found. Females (68.3%) were
      predominant over males (31.7%), and a mean age of under 30 years of age. The most
      frequent diagnosis on release was "pregnancy, childbirth and post-partum-related
      complications", totaling 37.7% of all releases, others involving, "injuries and
      poisoning" (12.9%), "digestive tract diseases" (7.8%) and "respiratory tract
      diseases" (5.4%), "Infectious and parasitic diseases" totaled 4.4%. CONCLUSIONS:
      The percentage of infectious and infectious-contagious diseases found did not
      contribute to encouraging the opinions disseminated regarding the importing or re
      emergence of diseases from the immigrant groups. The en masse immigration which
      has taken place requires many adaptations of the Healthcare System to afford the
      possibility of setting out the health profile for this group based on population
      estimates.

PMID- 14965064
TI  - [Evolution of antipsychotic drug consumption in the autonomous community of
      Castile and Leon, Spain (1990-2001)].
AB  - BACKGROUND: Over the past ten years, new drugs and new approaches to treatment
      have been implemented making it possible to assume changes in the use of
      antipsychotic drugs in our environment. This study is aimed at characterizing the
      pattern of use of antipsychotic drugs in Castile and Leon throughout the 1990
      2001 period as well as ascertaining the bearing which the marketing of new
      antipsychotic drugs may have had on the pattern of consumption of these drugs.
      METHODS: The drug consumption data was obtained from the Ministry of Health and
      Consumer Affairs' consumption database ECOM (Especialidades Consumo de
      Medicamentos). This database contains information on the consumption of
      medications dispensed charged to the Social Insurance system in community
      pharmacies nationwide. To estimate the consumption outside of the National Health
      System, data from the IMS (International Marketing Services) firm for the years
      2000 and 2001 was used. The data was given in Defined Daily Doses/1000
      inhabitants/day. RESULTS: The use of antipsychotic drugs rose by 146% within the
      1990-2001 period. Throughout the period studied, haloperidol was the
      antipsychotic drug most used in Spain and in Castile and Leon. The atypical
      antipsychotic drugs totaled 49% of the total consumption for 2001 and 90% of the
      costs, a strong trend being found toward an increase in the consumption of these
      atypical antipsychotic drugs in detriment to the typical antipsychotic drugs. It
      has been estimated that 14% of the antipsychotic drugs used in Castile and Leon
      were used outside of the National Health System.. Appreciable differences exist
      among the different provinces. CONCLUSIONS: The consumption of antipsychotic
      drugs in Castile and Leon grew by 146% throughout the twelve months studied. The
      marketing of new atypical antipsychotic drugs and the legal measures related to
      the deinstitutionalization of mental patients may have played a major role in
      this increase. The marketing of the new antipsychotic drugs has led to a change
      in their pattern of use and has give rise to an rise in the direct costs. The
      consumption of these medications not charged to the National Health System is
      minor, but not negligible.

PMID- 14965065
TI  - [Profile of the Emergency demand and influence of televised soccer games on an
      extra-hospital center in the Tafalla health care district. Navarre, Spain].
AB  - BACKGROUND: The demand placed on both hospital as well as extrahospital emergency
      care units currently continues to increase at a growing rate. This study has a
      twofold objective: the quantification and study of the personal characteristics
      of the users who are demanding emergency care and assessing whether televised
      soccer games have any bearing on the utilization of emergency care services.
      METHODS: A longitudinal descriptive study (9,723 users demanding care) and study
      of cases and controls (1,284 users demanding care) according to whether or not a
      soccer game was being televised by means of a logistic regression model. The
      associations were quantified by means of the odds ratio (OR). Those dealt with by
      telephone or in infirmaries were not included in the study. RESULTS: A total
      10.6% of the demand involved home visits, 4.8% of this total having been sent to
      hospital. A total 13.3% of the demand corresponds to individuals visiting from
      other healthcare districts, a total of 65 being overusers of emergency care (8 or
      more visits). The month of August (32.3%). Sundays (44.56%) and the 12:00 p.m.
      2:00 p.m. timeframe (8.38%) are the times when the greatest demand for care
      occurs, the differences being statistically significant. Televised soccer games
      were associated to a 19.8% (p < 0.001) rise in demand as compared to the control
      period. CONCLUSIONS: A high degree of use of the extrahospital emergency care
      units has been found to exist, a major part of the demand being concentrated at
      highly specific points in time. A major degree of care is provided to those
      visiting from outside their own healthcare districts. Television soccer game
      broadcasts is associated with the greater utilization of the emergency care
      services.

PMID- 14965066
TI  - [Microbiological study of the meals served in school lunch rooms on the island of
      Tenerife, Spain].
AB  - BACKGROUND: School lunchrooms and catered meals are of major importance from the
      Public Health standpoint. This study is aimed at evaluating the microbiological
      quality of the meals served in school lunchrooms for the purpose of ascertaining
      whether it is suitable or, to the contrary, the intake thereof may involve a
      serious health problem for this high-risk group. METHODS: A transversal
      descriptive epidemiological study. An analysis was conducted of a total of 898
      food samples collected from the lunchrooms at 101 schools in Tenerife, selected
      by a stratified random probabillistic sampling procedure, fifty-eight of which
      were prepared at the school proper (direct management) and 43 involving meals
      served by a catering firm (prepared under contract). RESULTS: No disease-causing
      Salmonella spp. or Listeria monocytogenes bacteria were isolated from any of the
      samples. A total 79% of the foods studies showed counts for this parameter, (91%)
      in salads and (85%) in main courses. A total 15% of the samples analyzed tested
      positive for total Enterobacteriaceae. Escherichia coli was isolated in 24% of
      the salads, in 4% of the side dishes and in 1% of the main dishes. Staphylococcus
      aureus having in isolated in three foods. The highest counts were found for the
      total aerobic mesophyllic microorganisms. A total 8.24% of the samples analyzed
      exceeded one or more of the limits stipulated for the parameters studies.
      CONCLUSIONS: The microbiological quality of the meals served in these school
      lunchrooms is acceptable, although due to a certain percentage of the foods
      having exceeded the stipulated limits for microorganisms indicative of and
      revealing a lack of hygiene, and school-children being a high-risk group, a
      revision of the surveillance related to critical checkpoints will be necessary.

PMID- 14965067
TI  - [Reduced sensitivity to ciprofloxacin in isolated enteric salmonella in the north
      zone of Huelva].

PMID- 14965068
TI  - [Importance of key words in bibliographic searches].

PMID- 14965069
TI  - [Vaccines and campaigns: images with a story to tell].

PMID- 14965070
TI  - Personal reflections on monochromators and action spectra for photoreactivation.
AB  - This is a summary of work done, chiefly by the author, in the mid-20th century,
      when monochromators were a primary tool in identification of molecules involved
      in biological effects, much as spectrometers were useful for molecular chemistry
      in the 19th and early 20th centuries. Monochromator types are discussed, as well
      as production of action spectra fro the chromophores for photoreactivation of
      ultraviolet biological effects. Two new types of non-enzymatic photoreactivation
      were found in prokaryotes, in addition to the classical enzymatic
      photoreactivation.

PMID- 14965071
TI  - [Proposal for the recovery of historiographic data: SESP/FSESP sources in the
      study of immunization campaigns in Brazil].

PMID- 14965072
TI  - Proceedings of the 1st International Conference on Chemoprevention of Prostate
      Cancer. San Antonio, Texas, USA, March 7-8, 2003.

PMID- 14965073
TI  - AHRQ's bioterrorism research portfolio: real linkages in real time.

PMID- 14965074
TI  - The challenge of studying the effects of managed care as managed care evolves.

PMID- 14965075
TI  - The impact of visit frequency on the relationship between service quality and
      outpatient satisfaction: a South Korean study.
AB  - OBJECTIVE: To examine the relative impact of four service quality dimensions on
      outpatient satisfaction and to test the invariance of the structural
      relationships between the service quality dimensions and satisfaction across
      three patient groups of varying numbers of prior visits to the same hospital as
      outpatients. DATA SOURCES/STUDY SETTING: Survey of 557 outpatients using a self
      administered questionnaire over a 10-day period at a general hospital in Sungnam,
      South Korea. DATA COLLECTION: Patients answered questions related to two main
      constructs, patient satisfaction and health care service quality. The health care
      service quality measures (30 items) were developed based on the results of three
      focus group interviews and the SERVQUAL scale, while satisfaction (3 items) was
      measured using a previously validated scale. STUDY DESIGN: Confirmatory factor
      analysis was used to assess the construct validity of the service quality scale
      by testing convergent and divergent validity. A structural equation model
      specifying the four service quality dimensions as exogenous variables and patient
      satisfaction as an endogenous variable was estimated to assess the relative
      impact of each of the service quality dimensions on satisfaction. This was
      followed by a multigroup LISREL analysis that tested the invariance of structural
      coefficients across three groups with different frequencies of outpatient visits
      to the hospital. PRINCIPAL FINDINGS: Findings support the causal relationship
      between service quality and satisfaction in the context of the South Korean
      health care environment. The four service quality dimensions showed varying
      patterns of impact on patient satisfaction across the three different outpatient
      groups. CONCLUSION: The hospital management needs to be aware of the relative
      importance of each of the service quality dimensions in satisfaction formation of
      outpatients, which varies across different hospital utilization groups, and use
      this in strategic considerations.

PMID- 14965076
TI  - Older persons' evaluations of health care: the effects of medical skepticism and
      worry about health.
AB  - OBJECTIVE: To describe how skepticism about medical care and other individual
      differences, including worry about health status, are associated with evaluations
      of health care among the noninstitutionalized elderly. DATA SOURCES/STUDY
      SETTING: Data were collected through a survey of approximately 5,000 community
      dwelling elders (aged 65 and older) in a southwestern region of the United
      States. STUDY DESIGN: Global evaluations of health care were measured with two
      items from the Consumer Assessment of Health Plans Study (CAHPS) instrument, an
      overall care rating (OCR) and a personal doctor rating (PDR). Multivariate
      ordered logit regression models were tested to examine how medical skepticism and
      other factors were associated with ratings of 0-7, 8-9, and 10. PRINCIPAL
      FINDINGS: Consumers who were skeptical of prescription drugs relative to home
      remedies, who held attitudes that they understand their health better than most
      doctors, and who worried about their health had worse OCR and PDR. Those who held
      attitudes that individual behavior determines how soon one gets better when sick
      had better PDR and OCR. CONCLUSIONS: Health policymakers, managers, and providers
      may need to consider the degree to which they should attempt to satisfy skeptical
      consumers, many of whom may never rate their care highly. Alternatively, they may
      need to target skeptical consumers with educational efforts explaining the
      benefits of medical care.

PMID- 14965077
TI  - Identifying children with special health care needs in the National Health
      Interview Survey: a new resource for policy analysis.
AB  - OBJECTIVE: To test the feasibility of using the National Health Interview Survey
      (NHIS) to identify children with chronic illness through a noncategorical
      approach, as exemplified by the Children with Special Health Care Needs (CSHCN)
      screener. The ability to use the NHIS to identify CSHCN will permit analyses of
      the effects of welfare reform and public insurance eligibility expansions during
      the late 1990s on CSHCN. DATA SOURCES: The NHIS from 1997, 1999, and 2000. The
      NHIS is an ongoing household survey representative of the civilian,
      noninstitutionalized population of the United States. STUDY DESIGN: Survey items
      were selected from the NHIS and thresholds designated to replicate the content
      and logic of the CSHCN screener. The screener asks explicit questions concerning
      an elevated need for, or use of health care services, and about limitations in
      activity, both caused by a chronic health condition. The algorithm created was
      applied to the pooled 1999-2000 NHIS to generate national prevalence estimates.
      Multivariate logistic regression was estimated to determine the effect of having
      particular demographic characteristics on the likelihood of being identified as
      CSHCN. Log odds ratios were compared to those from earlier NHIS-based estimates
      and from a pretest of the CSHCN screener. PRINCIPAL FINDINGS: An estimated 12
      percent of noninstitutionalized children aged 0 through 17 have a chronic
      condition that results in elevated service use or limitations in normal activity.
      This estimate is sensitive to inclusion of children with a broader array of less
      serious or shorter-term conditions. The estimated effects of child
      characteristics on the likelihood of being identified as having special health
      needs are similar but not identical to other algorithms that have been used to
      identify CSHCN. CONCLUSIONS: It is feasible to use existing questions in the NHIS
      to identify a population of CSHCN that is substantially similar to children
      identified through other algorithms or through use of a screening instrument
      imbedded in a household survey. The availability of this algorithm will permit
      use of the NHIS for important analyses of the effects of welfare reform and
      public insurance expansions on children with special health care needs.

PMID- 14965078
TI  - Profile of medical charges for children by health status group and severity level
      in a Washington State Health Plan.
AB  - OBJECTIVE: To identify children and evaluate patterns of charges for pediatric
      medical care, by overall health status, severity of illness, and categories of
      medical service. Data Sources Enrollment, claims, and charges data from a
      Washington State health plan. The study population includes all children ages 0
      to 18 years during calendar year 1999. STUDY DESIGN: Children were classified
      into clinically defined health status groups and severity levels using Clinical
      Risk Groups (CRGs). Health plan charges were analyzed according to core health
      status group, severity level, and category of service. DATA COLLECTION: The three
      secondary data sources were obtained electronically from the health plan and
      cleaned for unique members and data quality before analysis. PRINCIPAL FINDINGS:
      Children classified as healthy (85.2 percent) had mean and median annual charges
      of dollar 485 and dollar 191. Children with one or more chronic conditions (9.5
      percent) had mean and median charges increasing by status and severity group from
      dollar 2,303 to dollar 76,143 and from dollar 1,151 to dollar 19,456, and
      accounted for 45.2 percent of all charges. Distribution of charges varied across
      health status groups. Healthy children had 70.6 percent of their charges in
      outpatient and physician services. Children classified in the complex,
      catastrophic, and malignancy groups had 67 percent of their charges in inpatient
      encounters. Children with chronic conditions accounted for 31.8 percent of all
      physician, 41.8 percent of outpatient, 47.7 percent of pharmacy, 60.7 percent of
      inpatient, and 75.8 percent of all other charges. CONCLUSIONS: Children with
      chronic conditions account for a disproportionately high percentage of children's
      health expenditures. They account for different percentages of expenses for
      different medical services. These percentages vary according to health status and
      severity. This analysis can be used to identify and track groups of children for
      various purposes.

PMID- 14965079
TI  - Do drug-free workplace programs prevent occupational injuries? Evidence from
      Washington State.
AB  - OBJECTIVE: To evaluate the effect of a publicly sponsored drug-free workplace
      program on reducing the risk of occupational injuries. DATA SOURCES: Workers'
      compensation claims data from the Washington State Department of Labor and
      Industries covering the period 1994 through 2000 and work-hours data reported by
      employers served as the data sources for the analysis. STUDY DESIGN: We used a
      pre-post design with a nonequivalent comparison group to assess the impact of the
      intervention on injury risk, measured in terms of differences in injury incidence
      rates. Two hundred and sixty-one companies that enrolled in the drug-free
      workplace program during the latter half of 1996 were compared with approximately
      20,500 nonintervention companies. We tested autoregressive, integrated moving
      average (ARIMA) models to assess the robustness of our findings. PRINCIPAL
      FINDINGS: The drug-free workplace intervention was associated (p < .05) with a
      statistically significant decrease in injury rates for three industry groups:
      construction, manufacturing, and services. It was associated (p < .05) with a
      reduction in the incidence rate of more serious injuries involving four or more
      days of lost work time for two industry groups: construction and services. The
      ARIMA analysis supported CONCLUSIONS: The drug-free workplace program we studied
      was associated with a selective, industry-specific preventive effect. The
      strongest evidence of an intervention effect was for the construction industry.
      Estimated net cost savings for this industry were positive though small in
      magnitude.

PMID- 14965080
TI  - The costs of decedents in the Medicare program: implications for payments to
      Medicare + Choice plans.
AB  - OBJECTIVE: To discuss and quantify the incentives that Medicare managed care
      plans have to avoid (through selective enrollment or disenrollment) people who
      are at risk for very high costs, focusing on Medicare beneficiaries in the last
      year of life-a group that accounts for more than one-quarter of Medicare's annual
      expenditures. DATA SOURCE: Medicare administrative claims for 1994 and 1995.
      STUDY DESIGN: We calculated the payment a plan would have received under three
      risk-adjustment systems for each beneficiary in our 1995 sample based on his or
      her age, gender, county of residence, original reason for Medicare entitlement,
      and principal inpatient diagnoses received during any hospital stays in 1994. We
      compared these amounts to the actual costs incurred by those beneficiaries. We
      then looked for clinical categories that were predictive of costs, including
      costs in a beneficiary's last year of life, not accounted for by the risk
      adjusters. DATA EXTRACTION METHODS: The analyses were conducted using claims for
      a 5 percent random sample of Medicare beneficiaries who died in 1995 and a
      matched group of survivors. PRINCIPAL FINDINGS: Medicare is currently
      implementing the Principal Inpatient Diagnostic Cost Groups (PIP-DCG) risk
      adjustment payment system to address the problem of risk selection in the
      Medicare+Choice program. We quantify the strong financial disincentives to enroll
      terminally ill beneficiaries that plans still have under this risk adjustment
      system. We also show that up to one-third of the selection observed between
      Medicare HMOs and the traditional fee-for-service system could be due to
      differential enrollment of decedents. A risk adjustment system that incorporated
      more of the available diagnostic information would attenuate this disincentive;
      however, plans could still use clinical information (not included in the risk
      adjustment scheme) to identify beneficiaries whose expected costs exceed expected
      payments. CONCLUSIONS: More disaggregated prospective risk adjustment methods and
      alternative payment systems that compensate plans for delivering care to certain
      classes of patients should be considered to ensure access to high-quality managed
      care for all beneficiaries.

PMID- 14965081
TI  - Impact of managed care on the treatment, costs, and outcomes of fee-for-service
      Medicare patients with acute myocardial infarction.
AB  - OBJECTIVE: To examine the effects of market-level managed care activity on the
      treatment, cost, and outcomes of care for Medicare fee-for-service acute
      myocardial infarction (AMI) patients. DATA SOURCES/STUDY SETTING: Patients from
      the Cooperative Cardiovascular Project (CCP), a sample of Medicare beneficiaries
      discharged from nonfederal acute-care hospitals with a primary discharge
      diagnosis of AMI from January 1994 to February 1996. STUDY DESIGN: We estimated
      models of patient treatment, costs, and outcomes using ordinary least squares and
      logistic regression. The independent variables of primary interest were market
      area managed care penetration and competition. The models included controls for
      patient, hospital, and other market area characteristics. DATA
      COLLECTION/EXTRACTION METHODS: We merged the CCP data with Medicare claims and
      other data sources. The study sample included CCP patients aged 65 and older who
      were admitted during 1994 and 1995 with a confirmed AMI to a nonrural hospital.
      PRINCIPAL FINDINGS: Rates of revascularization and cardiac catheterization for
      Medicare fee-for-service patients with AMI are lower in high-HMO penetration
      markets than in low-penetration ones. Patients admitted in high-HMO-competition
      markets, in contrast, are more likely to receive cardiac catheterization for
      treatment of their AMI and had higher treatment costs than those admitted in low
      competition markets. CONCLUSIONS: The level of managed care activity in the
      health care market affects the process of care for Medicare fee-for-service AMI
      patients. Spillovers from managed care activity to patients with other types of
      insurance are more likely when managed care organizations have greater market
      power.

PMID- 14965083
TI  - Moving beyond the typologies of managed care: the example of health plan
      predictors of screening mammography.
AB  - OBJECTIVES: To develop a framework of factors to characterize health plans, to
      identify how plan characteristics were measured in a national survey, and to
      apply our findings to an analysis of the predictors of screening mammography.
      DATA SOURCE: The primary data were from the 1996 Medical Expenditure Panel
      Survey. STUDY DESIGN: Women ages 40+, with private insurance, and no history of
      breast cancer were included in the study (N = 2,909). We used multivariate
      logistic regression to estimate mammography utilization in the past two years
      relative to health plan and demographic factors. Health plan measures included
      whether there is a defined provider network, whether coverage is restricted to a
      network, use of gatekeepers, level of cost containment, copayment and deductible
      amounts, coinsurance rate, and breadth of benefit coverage. PRINCIPAL FINDINGS:
      We found no significant difference in reported mammography utilization using a
      dichotomous comparison of individuals enrolled in managed care versus indemnity
      plans. However, women in health plans with a defined provider network were more
      likely to report having received a mammogram in the past two years than those
      without networks (adjusted OR= 1.21, 95 percent CI = 1.07-1.36), and women in
      gatekeeper plans were more likely to report receiving mammography than those
      without gatekeepers (adjusted OR = 1.18, 95 percent CI = 1.03-1.36). Restricted
      out-of-network coverage, use of cost containment, enrollee cost sharing, and
      breadth of benefit coverage did not appear to affect mammography use.
      CONCLUSIONS: It is important to examine the effect of individual health plan
      components on the utilization of health care, rather than use the traditional
      broader categorizations of managed versus nonmanaged care or simple health plan
      typologies.

PMID- 14965082
TI  - Are gatekeeper requirements associated with cancer screening utilization?
AB  - OBJECTIVE: There is widespread debate over whether health plans should require
      enrollees to use "gatekeepers," which are primary care providers that coordinate
      care and control access to specialists. However, little is known about whether
      health plan gatekeeper requirements improve or reduce quality-of-care. Our
      objective was to examine whether gatekeeper requirements are associated with the
      utilization of cancer screening for breast, cervical, and prostate cancer. DATA
      SOURCES: Three linked sources (N = 13,534): (1) 1996 Medical Expenditure Panel
      Survey (MEPS) Household Survey, a nationally representative, ongoing survey
      sponsored by the Agency for Healthcare Research and Quality; (2) 1996 MEPS Health
      Insurance Plan Abstraction, which codes data from health plan booklets obtained
      from privately insured respondents, and (3) 1995 National Health Interview
      Survey. STUDY DESIGN/DATA COLLECTION: Cross-sectional, multivariate logistic
      regression analysis using secondary data. PRINCIPAL FINDINGS: We found in
      multivariate analyses that women in gatekeeper plans were significantly more
      likely to obtain mammography screening (Odds Ratio [OR] = 1.22, 95 percent
      Confidence Interval [CI] 1.07-1.40), clinical breast examinations (OR = 1.39, 95
      percent CI 1.23-1.57), and Pap smears (OR = 1.33, 95 percent CI 1.16-1.52) than
      women not in gatekeeper plans. In contrast, gatekeeper requirements were not
      associated with prostate cancer screening (OR = 1.11, 95 percent CI 0.93-1.33).
      We found no association between screening utilization and aggregate plan types
      (HMO, POS, PPO, FFS). CONCLUSIONS: Gatekeeper requirements are associated with
      higher utilization of widely recommended cancer screening procedures, but not
      with utilization of a less uniformly recommended cancer screening procedure.
      Researchers should consider the analysis of specific plan characteristics rather
      than aggregate plan types in conducting future research, and insurers and
      policymakers should consider the potential benefits of gatekeepers with respect
      to preventive care when designing health plans and legislation.

PMID- 14965084
TI  - Reexamining organizational configurations: an update, validation, and expansion
      of the taxonomy of health networks and systems.
AB  - OBJECTIVES: To (a) assess how the original cluster categories of hospital-led
      health networks and systems have changed over time; (b) identify any new patterns
      of cluster configurations; and (c) demonstrate how additional data can be used to
      refine and enhance the taxonomy measures. DATA SOURCES; 1994 and 1998 American
      Hospital Association (AHA) Annual Survey of Hospitals. STUDY DESIGN: As in the
      original taxonomy, separate cluster solutions are identified for health networks
      and health systems by applying three strategic/structural dimensions
      (differentiation, integration, and centralization) to three components of the
      health service/product continuum (hospital services, physician arrangements, and
      provider-based insurance activities). DATA EXTRACTION METHODS: Factor, cluster,
      and discriminant analyses are used to analyze the 1998 data. Descriptive and
      comparative methods are used to analyze the updated 1998 taxonomy relative to the
      original 1994 version. PRINCIPAL FINDINGS: The 1998 cluster categories are
      similar to the original taxonomy, however, they reveal some new organizational
      configurations. For the health networks, centralization of product/service lines
      is occurring more selectively than in the past. For the health systems,
      participation has grown in and dispersed across a more diverse set of
      decentralized organizational forms. For both networks and systems, the definition
      of centralization has changed over time. CONCLUSIONS: In its updated form, the
      taxonomy continues to provide policymakers and practitioners with a descriptive
      and contextual framework against which to assess organizational programs and
      policies. There is a need to continue to revisit the taxonomy from time to time
      because of the persistent evolution of the U.S. health care industry and the
      consequent shifting of organizational configurations in this arena. There is also
      value in continuing to move the taxonomy in the direction of refinement/expansion
      as new opportunities become available.

PMID- 14965085
TI  - Do heavy broiler chickens visit automatic weighing systems less than lighter
      birds?
AB  - 1. In previous studies it was found that automatic broiler weighing systems can
      have accuracy problems. Researchers reported poor agreement between automatic and
      manual mean weighing used as a reference. The difference was observed especially
      after 4 to 5 weeks and this was explained by assuming that heavier birds visited
      the weighing system less at the end of the growing period. 2. Our study tested
      this hypothesis under practical production conditions. 3. In total, 193,536
      digital images of broilers on and in the neighbourhood of the platforms were
      collected over three growing periods of 6 weeks. The area (upper view) of the
      broilers was calculated using image analysis techniques. 4. The hypothesis that
      the weighing system was used less frequently by heavier animals was confirmed.
      More specifically, statistical differences between the area of broilers on and in
      the neighbourhood of the weighing system could be demonstrated for week 5.

PMID- 14965086
TI  - Intra-farm variation of rodent infestations on poultry farms of central
      Argentina.
AB  - 1. During the summer and winter of 1998 we monitored rodent infestation in the
      sheds of 9 poultry farms in central Argentina to estimate variation in rodent
      infestation within farms and its possible association with shed structure and
      farm design. 2. We observed great heterogeneity in rodent infestations, with a
      mean variation of 37% in the 'Rodent Infestation Index' (RII; an estimate of
      rodent density revealed by tracks) between sheds of the same farm. 3. In summer,
      the group of sheds that showed the highest RII had a higher chicken density than
      the group of sheds with the lowest RII. Sheds located between other sheds of the
      same farm showed a lower RII than sheds located beside the perimeter of the farm.
      4. Our results support the hypothesis that rodents show habitat selection at both
      macro (farm) and microhabitat (shed) scales, and that the variables associated
      with these associations can change according to the scale. 5. Our observation
      that sheds located beside the perimeter of the farms are prone to rodent
      invasions reinforces our previous recommendation that farms with an efficient
      control of vegetation growth around their perimeter would have appreciably lower
      rodent infestations.

PMID- 14965087
TI  - Ultrastructural study of spermiogenesis in the turkey, Meleagris gallopavo.
AB  - 1. Ultrastructural changes that take place in the spermatids of the turkey were
      studied. Twelve steps of spermiogenesis are described. 2. Acrosomal formation is
      similar to that in the domestic fowl and quail. The perforatorium develops as a
      dense granule in a tubular invagination of the thickened part of the nuclear
      membrane during the acrosomal phase of spermatid development. 3. Patchy
      appearances of the circular (CM) and longitudinal (LM) manchette occur
      concurrently for a very brief period before the complete disappearance of the
      former and full establishment of the latter, an indication that the CM
      reorganises to become the LM. 4. A chromatoid body, as found in mammals, is
      present in the mid-piece of the turkey spermatid, and glycogen aggregations occur
      in the spermatid cytoplasm, but not in the mature spermatid or spermatozoon. 5.
      Mitochondrial alignment around the axoneme in the mid-piece takes place only
      after the dissolution of the LM, unlike in the Japanese quail. 6. The merits and
      disadvantages of the 4-phase and step-wise systems of spermatid classification
      and evaluation are discussed.

PMID- 14965088
TI  - Effects of dietary particulate limestone, vitamin K3 and fluoride and
      photostimulation on skeletal morphology and osteoporosis in laying hens.
AB  - 1. Female chicks of a White Leghorn strain were fed three different diets from
      one day old: control, additional vitamin K3 (10 mg/kg), and a diet containing a
      combination of additional vitamin K3, sodium fluoride (10 mg/kg) and limestone in
      particulate rather than powdered form. At 16 weeks photoperiod was increased for
      half the birds from 8:16 L:D to 16:8 L:D immediately or by one hour per week to
      the same ultimate photoperiod for the other half. 2. Age at first egg was lower
      by 4.0 d for birds on the fast lighting regime but there were no overall effects
      of lighting on bone quality at either 25 or 70 weeks. 3. Additional vitamin K3
      resulted in higher proximal tarsometatarsus cancellous bone volumes at 15 weeks
      and throughout the laying period compared with controls. Plasma osteocalcin
      concentrations were unaffected by vitamin K3 supplementation during growth. 4.
      The combination diet resulted in beneficial responses of 12 to 20% in most bone
      characteristics in hens at 70 weeks. The magnitude of these effects was similar
      to a previous study involving a particulate calcium source alone (Fleming et al.,
      Poultry Science, 39: 434-440, 1998b). We conclude that the beneficial effects of
      the combined treatment over the lifetime of the hens were attributable mainly to
      the presence in the diet of a calcium source in particulate form.

PMID- 14965089
TI  - Prenatal exposure to corticosterone impairs embryonic development and increases
      fluctuating asymmetry in chickens (Gallus gallus domesticus).
AB  - 1. The level of corticosterone in fertilised eggs from hens (Gallus gallus
      domesticus) was manipulated experimentally to elucidate whether stress in laying
      hens is harmful to the chicks, as manifested by impaired survival and reduced
      growth, and whether bilateral asymmetry may represent an indicator of
      environmental stress in poultry. 2. Three hundred and fifty eggs were randomly
      divided into 4 groups; 1. untreated, 2. control, 3. 10 ng corticosterone/ml and
      4. 20 ng corticosterone/ml. Each of the eggs in groups 2, 3 and 4 were injected
      with 100 microl ethanol-saline solution (25% ethanol in saline) containing 0, 0.6
      and 1.2 microg corticosterone, respectively. After the injections, the final
      concentration of ethanol in the egg (albumen and yolk) was 0.03%, and the
      concentration of added corticosterone was 0, 10 and 20 ng/ml, respectively, in
      groups 2, 3 and 4. All the eggs were treated on developmental d 1. 3.
      Corticosterone injections resulted in greater embryonic mortality, earlier
      termination of foetal development and reduced growth. Moreover, chicks developing
      in eggs with an elevated concentration of corticosterone displayed reduced
      developmental stability as evidenced by increased fluctuating asymmetry (FA) in
      tarsus length. 4. In conclusion, an increased concentration of corticosterone in
      the egg was detrimental to survival and growth of the chicks. Prenatal stress
      also generated bilateral asymmetry, and illustrates the potential application of
      FA as an indicator of environmental stress in poultry.

PMID- 14965090
TI  - Quantitative feed restriction or meal-feeding of broiler chicks alter functional
      development of enzymes for protein digestion.
AB  - 1. Two experiments were performed on broiler chicks to determine the effect of
      either quantitative feed restriction (QFR) from 5 to 11 d of age or meal-feeding
      (MF) from d 5 to 17 on development of activity of enzymes associated with protein
      digestion. 2. Proteolytic activity of the proventriculus was reduced by QFR but
      unaffected by MF. 3. General proteolytic and carboxypeptidase A activities of the
      pancreas were reduced by QFR and MF. 4. Amino- and dipeptidase activities of the
      small intestine were increased by QFR. Dipeptidase activity was unaffected by MF.
      5. Nitrogen retention of QFR chicks was lower immediately following feed
      restriction but not in the 2 weeks following return to ad libitum access to feed.
      6. Feeding regimen alters functional development of the enzymes of protein
      digestion and may therefore influence growth rate of broilers.

PMID- 14965091
TI  - Effects of microbial phytase, produced by solid-state fermentation, on the
      performance and nutrient utilisation of broilers fed maize- and wheat-based
      diets.
AB  - 1. The influence of a microbial phytase on the performance, toe ash contents and
      nutrient utilisation of male broilers fed diets based on maize and wheat was
      investigated. The experiment was conducted as 2 x 2 x 2 factorial arrangement of
      treatments. Within the factorial, two diet types (maize-soy or wheat-soy)
      containing two levels of non-phytate phosphorus (3.0 or 4.5 g/kg) were evaluated
      and each level of non-phytate phosphorus was supplemented with 0 or 500 PU
      phytase/kg diet. Each of the 8 dietary treatments were fed to 6 pens of 8 birds
      from d 1 to 21 post-hatching. 2. Main effects of diet type and phytase were
      observed for all parameters. Main effect of non-phytate phosphorus was
      significant only for feed/gain and toe ash contents. Phytase addition improved
      weight gains irrespective of diet type or non-phytate phosphorus level, but the
      magnitude of improvement in the phosphorus-deficient wheat-soy diet was greater,
      resulting in a diet type x non-phytate phosphorus interaction. Responses in toe
      ash contents were noted only in phosphorus-deficient diets, as indicated by a non
      phytate phosphorus x phytase interaction. 3. Phytase addition improved apparent
      metabolisable energy values of wheat-based diets, but had little effect on the
      apparent metabolisable energy of maize-based diets as shown by a diet type x
      phytase interaction. The apparent metabolisable energy was not influenced by
      dietary non-phytate P. 4. Phytase improved ileal nitrogen digestibility in both
      diet types, but the responses to added phytase tended to be higher in wheat-based
      diets, as shown by a diet type x phytase interaction. 5. Increasing the dietary
      non-phytate phosphorus level reduced phosphorus digestibility and increased
      excreta phosphorus content. Addition of phytase improved phosphorus
      digestibility, but the increments were higher in low phosphorus diets resulting
      in a non-phytate phosphorus x phytase interaction. Phytase addition tended to
      lower the excreta phosphorus content, but the effects were greater in birds fed
      low phosphorus diets, as shown by a non-phytate phosphorus x phytase interaction.

PMID- 14965092
TI  - Endogenous losses of energy and amino acids in birds and their effect on true
      metabolisable energy values and availability of amino acids in maize.
AB  - 1. Endogenous losses of amino acids (EAAL) and energy (EEL) were determined in
      unfed adult cockerels. The intercepts of linear regression analysis were
      determined using 44 birds precision-fed on maize. During the experimental period
      (48 h), excreta of birds were collected, and the samples of maize and the excreta
      were dried, ground and assayed for gross energy and amino acids. 2. The EAAL and
      EEL in unfed cockerels influenced true available amino acid (TAAA) values.
      Therefore, the intercept of regressions showed an increase in TAAA values of
      maize. 3. The results indicated that there was no significant difference between
      the data obtained for EEL from the unfed birds and from regression analysis so,
      the figure from regression analysis could be used for calculating the true
      metabolisable energy (TME) value of maize. 4. The calculated EAAL from regression
      analysis caused an increase in the TAAA value in maize. The amounts of metabolic
      and endogenous amino acid excretions varied in voided excreta from unfed birds.
      These differences would be related to genetics, age, sex and environmental
      temperatures.

PMID- 14965093
TI  - Early growth and environmental implications of dietary zinc and copper
      concentrations and sources of broiler chicks.
AB  - 1. Environmental accumulation of zinc and copper is becoming a concern in areas
      having intensive animal production. This study examined performance and excretion
      of broiler chicks given diets supplemented with graded concentrations of zinc and
      copper from three different sources. 2. Two experiments were conducted, each
      utilising 570 1-d-old chicks. In Experiment 1, chicks were given diets containing
      supplemental zinc concentrations from 40 to 120 mg/kg supplied as zinc sulphate,
      a zinc amino acid complex (Availa Zn), or a combination of zinc sulphate and
      Availa Zn with each contributing one-half of the total supplemental zinc. In
      Experiment 2, broiler chicks were given diets with graded concentrations of
      supplemental copper ranging from 4 to 12 mg/kg from copper sulphate, a copper
      amino acid complex (Availa Cu), or a combination of copper sulphate and Availa Cu
      with each contributing one-half of the total supplemental copper. 3. During the
      17-d experimental period, mineral concentration or source did not influence body
      weight, feed conversion, or the incidence of mortality from 1 to 17 d. 4.
      Decreasing dietary zinc concentration from 120 to 40 mg/kg reduced zinc excretion
      by 50%. 5. Copper excretion was decreased by 35% as supplemental copper was
      reduced from 12 to 4 mg/kg. 6. Reducing dietary zinc and copper concentrations
      can potentially decrease the accumulation of heavy metals in the environment
      without compromising bird performance.

PMID- 14965094
TI  - The long-term effects of using a higher amount of iodine supplement on the
      efficiency of laying hens.
AB  - 1. Two different levels of dietary iodine supplement (K + 0, 3.57 mg/kg; K + I,
      6.07 mg/kg) were used in a 52-week experiment using 32 ISA Brown laying hens. 2.
      The greater iodine content in the diet impaired the egg production (K + 0, 319.9
      +/- 1.31 eggs/hen; K + I, 312.4 +/- 4.19 eggs/hen), the egg weight (K + 0, 64.4 +
      0.66 g; K + I, 63.1 +/- 0.61 g) and the food to egg mass ratio (K + 0, 2.13 +/-
      0.023 kg/kg; K + I, 2.22 +/- 0.030 kg/kg). 3. The greater dietary iodine content
      had significant (P<0.05) negative effects on Haugh units, yolk index and eggshell
      weight.

PMID- 14965095
TI  - The effect of dietary fibre on the small intestines and apparent digestion in the
      turkey.
AB  - 1. In order to determine the feasibility of using high fibre diets in turkey
      rations, three crude fibre dietary concentrations were fed to turkey hens at
      three ages and performance, fibre digestibility and small intestinal morphology
      were determined. 2. Growth rate and feed efficiency decreased when diets
      contained 80 to 90 g crude fibre/kg; however, growth did not change when 60 g
      crude fibre/kg was fed between 1 and 4 weeks or between 6 and 8 weeks and was
      enhanced between 11 and 14 weeks of age. 3. Digestibilities of crude protein, fat
      and gross energy (GE) were depressed at fibre intakes of 80 to 90 g/kg between 1
      and 4 weeks but not at later ages. Crude fibre digestibility increased with age
      and decreased with dietary fibre content. 4. Total small intestinal length and
      surface area were increased by high dietary crude fibre intake between 11 and 14
      weeks. Small but inconsistent changes in the length, diameter and number of
      villi, villus size and area were observed in the duodenum, jejunum and ileum at
      the different ages as a result of feeding the different crude fibre
      concentrations. 5. Crude fibre can be utilised to some extent by turkeys and
      concentrations of 60 g fibre/kg in the diet did not result in decreased
      performance after 6 weeks of age.

PMID- 14965096
TI  - Dietary methionine requirement of the Chinese egg-laying duck.
AB  - 1. The dietary methionine requirement of egg-laying ducks was assessed by feeding
      diets supplemented with graded levels of DL-methionine (0, 4, 8, 12, 16 g/kg
      dietary protein) for 8 weeks. The basal diet contained 175 g protein and 2.6 g
      methionine per kg feed (or 14.9 g/kg protein) and an estimated ME of 11.5 MJ/kg.
      2. A total of 800 Shaoxin laying ducks (420 d old) were randomly divided into 5
      groups of 160 each and fed in 4 separate pens. 3. Dietary supplementation of
      methionine significantly increased egg production and feed conversion efficiency.
      4. Dietary methionine requirement for optimum egg production was estimated to be
      25.7 g/kg of dietary protein or 4.5 g/kg of the diet or 380 mg/bird-d. 5.
      Methionine supplementation increased the methionine level in plasma, and the free
      glutamic acid and aspartic acid concentrations in plasma were quadratically
      related to dietary methionine levels. Increasing dietary methionine had little
      effect on egg quality characteristics.

PMID- 14965097
TI  - Insulin-glucose interactions characterised in newly hatched broiler chicks.
AB  - 1. A study was conducted to identify the specificity of insulin-glucose
      interactions in newly hatched broiler chicks. 2. Plasma insulin concentrations in
      fed chicks at one day post-hatch were lower than those at later ages and tended
      to increase up to d 7, while the concentrations from 1 to 7 d of age were lower
      than those in chickens of 10 to 28 d of age. 3. Plasma glucose concentrations
      were lowered for 60 min by injection of insulin at 10 and 40 microg/kg body
      weight (BW) in both 1- and 21-d-old chicks, showing that the hypoglycaemic effect
      of exogenous insulin is of larger magnitude but shorter duration in 1-d-old
      chicks. 4. The decrease in plasma glucose concentration at 60 min after insulin
      injection (10 and 40 microg/kg BW) was larger in 1- to 7-d-old chicks than in 14-
      to 21-d-old chickens. 5. These results indicate that newly hatched broiler chicks
      are under the control of specific insulin-glucose interactions characterised by
      low plasma insulin concentrations with high sensitivity to insulin.

PMID- 14965098
TI  - An improved mathematical model of the ovulatory cycle of the laying hen.
AB  - 1. The mathematical model of the hen's ovulatory cycle proposed by Etches and
      Schoch (British Poultry Science, 25: 65-76, 1984) predicts ovulation times for
      sequences of 2 to 9 ovulations only. 2. Continuous functions have been produced,
      representing the changes required to the parameters lambda1, lambda2, S1, S2, b1,
      b2 and b3, such that the prediction of any sequence length is now possible. 3.
      This improved ovulation model is capable of predicting ovulation times and intra
      sequence ovulation intervals for any ovulation rate between 0.5 and 1.0. 4. The
      improved ovulatory model lends itself to stochasticity. The rate of lay of a
      population of hens at a time may be modelled with the use of means and standard
      errors for each of the parameters in the model. 5. Age-related changes in the
      ovulation rate of the population may be predicted using a combination of three
      methods, which are consistent with published theories that account for the
      decline in performance with time.

PMID- 14965099
TI  - Simultaneous measurements of instantaneous heart rate and breathing activity in
      newly hatched chicks.
AB  - 1. Among three types of fluctuations of instantaneous heart rate (IHR) found
      previously in newly hatched chicks, a high frequency oscillation with a mean
      frequency of about 0.7 Hz (Type I) appeared to be concurrent with breathing
      (Moriya et al., Comparative Biochemistry and Physiology, 124A: 461-468, 1999). 2.
      In order to confirm that Type I HR fluctuation is respiratory sinus arrhythmia
      (RSA), breathing activity was measured by a condenser microphone, simultaneously
      with IHR. 3. The microphone detected pressure changes caused by breathing
      (acoustorespirogram, ARG) and also unexpectedly movement, probably twitch, of
      hatchlings. 4. Simultaneous measurements of IHR and ARG demonstrated that
      oscillatory frequency of Type I HR fluctuation coincided with breathing frequency
      and IHR increased with inspiration, confirming that Type I HR oscillation is RSA.
      5. In addition, large transient HR accelerations (Type III HR fluctuation)
      simultaneously occurred with movement or twitch of the hatchlings, suggesting
      that Type III HR fluctuation and movement of hatchlings have the same origin,
      probably sympathetic nerve function.

PMID- 14965100
TI  - Effect of the hygienic status of poultry houses on performance and production.

PMID- 14965101
TI  - Effect of a lighting programme change on two breeds of laying hens.

PMID- 14965102
TI  - Poultry and pig farmers' respiratory symptoms.

PMID- 14965103
TI  - A comparison of welfare, health and production performance of laying hens reared
      in cages or in aviaries.

PMID- 14965104
TI  - Effect of providing 'whole wheat' in the diet on pecking behaviour in turkeys.

PMID- 14965105
TI  - Effect of housing systems on the bacterial flora of the air.

PMID- 14965106
TI  - Influence of olfaction on initial weight gain in two genotypes of chicks.

PMID- 14965107
TI  - Preliminary studies of the monitoring of Dermanyssus gallinae in free-range
      poultry farms.

PMID- 14965108
TI  - Effect of moult on eggshell quality.

PMID- 14965109
TI  - Relationships between pH, colour and technological behaviour of brined cooked
      breast of chicken.

PMID- 14965110
TI  - Patterns of chicken consumption in South-East China.

PMID- 14965111
TI  - Influence of nitrite and vitamin E percentage on myoglobin and lipid oxidation in
      packaged cooked cured-hams.

PMID- 14965112
TI  - Effect of rate of pH fall on turkey breast meat quality.

PMID- 14965113
TI  - Effect of housing systems on the bacterial flora of egg shells.

PMID- 14965114
TI  - Post treatment effects of a SANOVA immersion treatment on turkey carcases and
      subsequent influence on recontamination and cross contamination of breast fillet
      meat during turkey processing.

PMID- 14965115
TI  - Genetic variability in the anti-microbial activity of hen egg white.

PMID- 14965116
TI  - A functional approach to fattening in chickens.

PMID- 14965117
TI  - Isolation and characterisation of microsatellite genetic markers from Peking and
      Muscovy ducks.

PMID- 14965118
TI  - The chicken cytogenetic map: an aid to microchromosome identification and avian
      comparative cytogenetics.

PMID- 14965119
TI  - A radiation hybrid panel and its use in developing a gene map of the chicken.

PMID- 14965120
TI  - Genetic variability of clutch length in dwarf layers: prospects for poultry
      breeding.

PMID- 14965121
TI  - In vitro effects of enzymes on the viscosity and non-starch polysaccharides of
      barley.

PMID- 14965122
TI  - Does the colour of the feed influence the choice of the turkey?

PMID- 14965123
TI  - Performance of turkeys fed low protein diets with or without L-threonine
      supplementation.

PMID- 14965124
TI  - Effect of heat treatment on the nutritional and microbiological value of laying
      hen feed.

PMID- 14965125
TI  - Effect of dietary protein concentration and amino acid profile on the production
      performance of broilers.

PMID- 14965126
TI  - Influence of the methodology of sampling content from different parts of the
      ileum on the values of apparent ileal digestibility in broiler chickens.

PMID- 14965127
TI  - Quantitative analytical traceability of phytogenic active principles.

PMID- 14965128
TI  - Effect of a citrus extract (NOR-SPICE AB) on broiler performances.

PMID- 14965129
TI  - Effect of a fatty acid distillate blend on growth and fat digestibility in
      broilers.

PMID- 14965130
TI  - Prediction of the metabolisable energy value of maize in adult cockerel.

PMID- 14965131
TI  - Nutritional value of three faba bean cultivars for broiler chickens and adult
      cockerels.

PMID- 14965132
TI  - Influence of the physical structure of the feed on the diet transition of
      turkeys.

PMID- 14965133
TI  - Relationships between crude protein content, starch content, specific weight,
      hardness, sprouting and the nutritive value of wheat for broiler chickens.

PMID- 14965134
TI  - Energy digestibility of different feeds in continuous or sequential feeding
      programme for broiler chickens.

PMID- 14965135
TI  - In vitro fertilisation of chicken oocytes after in vitro ovulation.

PMID- 14965136
TI  - Persistence of reproductive performance in the Muscovy duck.

PMID- 14965137
TI  - Depletion of oxytetracycline in tissues of turkeys following administration of an
      oral soluble powder in drinking water (Tetratime).

PMID- 14965138
TI  - Preliminary data of adenovirus CELO localisation in chicken.

PMID- 14965139
TI  - Efficacy of a recombinant vaccine HVT-VP2 against Gumboro disease in the presence
      of maternal antibodies.

PMID- 14965140
TI  - Interest of anticoccidial sensitivity tests (ASTs) in the prevention of chicken
      coccidiosis.

PMID- 14965141
TI  - Changes in Salmonella enteritidis contamination in two layer lines vaccinated
      during the rearing period.

PMID- 14965142
TI  - Use of dichloromethylene bisphosphonate (Cl2MBP) to deplete macrophage function
      in the chicken.

PMID- 14965143
TI  - Experimental challenge model with low pathogenic H7N1 avian influenza virus to
      assess protection against infection by these viruses.

PMID- 14965144
TI  - Grassroots lobbying: an important tool for pharmacy. Developing grassroots
      advocate.

PMID- 14965145
TI  - Pharmacy through the ages. Origins of gelatin capsules.

PMID- 14965146
TI  - Pharmacy benefit manager 'spread': a reasonable, rational, realistic business
      practice.

PMID- 14965147
TI  - What's in a drug name?

PMID- 14965148
TI  - The spread: pilot study of an undocumented source of pharmacy benefit manager
      revenue.
AB  - OBJECTIVE: To document the difference between what pharmacy benefits management
      companies (PBMs) charge employers and what they pay dispensing pharmacies for the
      drug ingredient portion of prescription transactions (the "spre DESIGN:
      Descriptive, cross-sectional study. PARTICIPANTS: Two large employer groups, each
      of which used a different PBM, and six independent community pharmacies
      participating in these plans during 2002. INTERVENTIONS: Two sets of financial
      records issued by each of two PBMs were reviewed retrospectively, including 129
      line-item prescription transactions billed to the employer and the line-item
      transaction information that accompanies the PBM payment to the dispensing
      pharmacy. MAIN OUTCOME MEASURE: Spread between drug ingredient cost billed to the
      employer by the PBM and drug ingredient cost paid to the dispensing pharmacy by
      the PBM for brand name versus generic drug products. RESULTS: For both PBMs, the
      mean (+/- SD) spread was dollar 12.29 +/- 27.93 per prescription, with a range of
      -dollar 1.67 to dollar 201.65. Considering all 129 transactions, the mean spreads
      for brand name and generic medications were significantly different from one
      another, with mean (+/- SD) spreads of dollar 4.65 +/- 10.47 and dollar 23.45 +/-
      39.47 per prescription, respectively. The two PBMs differed significantly in
      their spreads for brand name drugs (dollar 3.20 +/- 2.85 and dollar 5.93 +/-
      14.12), but the spreads for generic products did not achieve statistical
      significance in absolute dollars (dollar 10.83 +/- 13.58 and dollar 31.74 +/-
      48.11) because of their greater variation (as reflected in the larger standard
      deviations). However, the percentages difference for generic products differed
      significantly. CONCLUSION: This pilot study indicates the possibility of
      substantial and widely varying differences in the spread and spread percentage
      between PBMs for brand name and generic medications. A more transparent business
      model for the PBM industry could produce better relations with PBM clients and
      business partners, including community pharmacies.

PMID- 14965149
TI  - Patient counseling provided in community pharmacies: effects of state regulation,
      pharmacist age, and busyness.
AB  - OBJECTIVE: To describe the nature and extent of patient counseling in community
      pharmacies and determine whether current counseling practices are influenced by
      pharmacist and pharmacy characteristics and variations in state regulation of
      patient counseling. DESIGN: Observational, cross-sectional study. SETTING: 306
      community pharmacies in eight states. PARTICIPANTS: Trained shoppers (acting as
      patients). INTERVENTIONS: Three new prescriptions were presented in each
      pharmacy, and regression techniques were used to analyze the effects of
      pharmacist age, pharmacy type, and busyness; whether written information was
      provided; and "intensity" of a state's patient counseling regulation as measured
      by its scope, stringency, and duration. MAIN OUTCOME MEASURES: Whether any or all
      of these events occurred: pharmacist talked with shopper, oral drug information
      was given, oral risk information was given, and/or questions were asked to assess
      shopper understanding; number of informational items mentioned (range 0-7) was
      also recorded. RESULTS: About 63% of the shoppers were given oral drug
      information (mean = 2.3 items). Shoppers with a younger responsible pharmacist
      were more likely than other shoppers to receive risk information, a higher number
      of informational items, and assessment of understanding. While pharmacy type was
      unrelated to counseling, busyness reduced the odds of any pharmacist talk, oral
      information-giving, and assessment of understanding. Counseling practices varied
      significantly according to the intensity of a state's counseling regulation, with
      frequency of any information provision climbing from 40% to 94% as states'
      counseling regulations increased in intensity. More intensive regulations also
      increased the likelihood of any pharmacist talk, any provision of risk
      information, any assessment of shopper understanding, and amount of oral
      information given. CONCLUSION: Counseling varied significantly according to
      intensity of state regulation, pharmacy busyness, and age of responsible
      pharmacist. These results present important challenges to state boards of
      pharmacy, pharmacy associations, managers, and individual practitioners who are
      in a position to improve this important element of patient care.

PMID- 14965150
TI  - Deficiencies of product labeling directions for the preparation of
      radiopharmaceuticals.
AB  - OBJECTIVE: To identify potential deficiencies in product labeling (package
      insert) instructions for the preparation of radiopharmaceuticals. METHODS:
      Preparation instructions, which include both reconstitution and quality control
      (QC) directions, as stated in the package inserts were evaluated for all
      commercially available reconstituted radiopharmaceuticals. Reviews of the package
      inserts were initially performed by each author, and then all identified
      deficiencies were compiled and evaluated by all authors. The preparation scenario
      for each package insert evaluated was based on a centralized nuclear pharmacy
      operation assuming typical support personnel, standard operating equipment, and
      workload. MAIN OUTCOME MEASURE: The instructions as stated in each package insert
      for the preparation (including QC) were rated as inadequate if a satisfactory
      preparation could not be prepared by a nuclear pharmacist or physician when
      instructions were followed exactly. RESULTS: Identified deficiencies in package
      insert instructions for the preparation of radiopharmaceuticals fell into the
      following five categories: (1) absent or incomplete directions (especially with
      regard to QC procedures); (2) restrictive directions (e.g., specific requirement
      to use designated needles, chromatography solvents, counting devices), (3)
      inconsistent directions (e.g., different reconstituted volumes for the same final
      drug product, unworkable expiration times); (4) impractical directions (e.g.,
      unrealistically low reconstituted activity limits, dangerously high number of
      radiolabeled particles); and (5) vague directions (e.g., use of the words
      "should," "may," "recommend"). CONCLUSION: Manufacturers' directions for the
      preparation of radiopharmaceuticals often contain deficiencies and should be
      viewed as standard guidance rather than as requirements. Just as physicians are
      permitted to use U.S. Food and Drug Administration (FDA)-approved drugs for off
      label indications, nuclear pharmacists should be allowed to use alternative
      methods for preparing radiopharmaceuticals, provided those methods have been
      validated to be as good as the stated directions and that the nuclear pharmacists
      do not engage in activities that fall outside the normal practice of pharmacy.
      Manufacturers, FDA, nuclear pharmacists, and nuclear physicians should work
      together to address identified deficiencies in package insert directions.

PMID- 14965151
TI  - National survey of dietary supplement resources at drug information centers.
AB  - OBJECTIVE: To assess the resources drug information centers are currently using
      to respond to dietary supplement information requests and to determine the
      frequency with which drug information centers are used as sources of information
      on dietary supplements. DESIGN: Cross-sectional survey. SETTING: United States.
      PARTICIPANTS: 116 drug information centers. INTERVENTIONS: Mail survey that
      collected information on the use of drug information centers for dietary
      supplement information requests and the dietary supplement-specific resources
      available at and used in these centers. MAIN OUTCOMES MEASURES: Survey responses,
      evaluated using descriptive statistics. RESULTS: Drug information centers
      received a relatively small number of requests for information related to dietary
      supplements, and most such requests came from consumers. The centers had a number
      of resources available to assist in responding to those requests, with Facts and
      Comparisons' The Review of Natural Products and the print version of Natural
      Medicines Comprehensive Database being the resources most often at hand. The
      majority of respondents believed their centers were "usually able" to respond to
      the requests received. CONCLUSION: Drug information centers are often overlooked
      as sources of information about dietary supplements; however, centers have
      resources that are, by self-assessment, sufficient to respond to dietary
      supplement information requests. Great variation exists among centers in the
      resources available to address requests, with just two resources, the Review of
      Natural Products and the print version of Natural Medicines Comprehensive
      Database, available to more than three-fourths of the respondents.

PMID- 14965152
TI  - Safety and tolerability of tegaserod in irritable bowel syndrome management.
AB  - OBJECTIVES: To discuss the need for safe and effective therapy for patients with
      irritable bowel syndrome (IBS) and to provide up-to-date information on the
      safety and tolerability profile of tegaserod, a novel treatment for women with
      IBS whose primary bowel symptom is constipation. DATA SOURCES: PubMed and
      abstracts from gastroenterology conferences were searched through October 2003
      using the following search terms: irritable bowel syndrome, IBS, tegaserod,
      cisapride, alosetron, systematic review, safety, tolerability, serotonin, 5-HT, 5
      HT3 receptor antagonist, and 5-HT4 receptor agonist; all information on the
      safety and tolerability of tegaserod published up to October 2003 is included.
      DATA SYNTHESIS: A comprehensive review of the medical literature (through 2001)
      finds no adequate therapies that address the multiple symptoms of IBS.
      Traditional agents, although occasionally effective, often cause adverse effects.
      Tegaserod, a selective serotonin type 4 receptor (5-HT4) partial agonist,
      overcomes a number of obstacles associated with traditional therapies. Important
      information for pharmacists about the safety and tolerability of tegaserod is
      presented. CONCLUSION: Tegaserod is effective in treating multiple IBS symptoms
      in women with IBS whose primary bowel symptom is constipation, and it is safe and
      well tolerated.

PMID- 14965153
TI  - Pharmacy through the ages. Medicinal leeches.

PMID- 14965154
TI  - Emerging treatments in oncology: focus on tyrosine kinase (erbB) receptor
      inhibitors.
AB  - OBJECTIVE: To describe the role of tyrosine kinase (TK) and its subreceptors in
      the development of cancer and the role of TK inhibitors in cancer treatment. DATA
      SOURCES: Published articles identified through MEDLINE using search terms such as
      tyrosine kinase, erbB1, erbB2, erbB3, erbB4, epidermal growth factor receptors
      (EGFR), and EGFR inhibitors. Additional sources were identified from
      bibliographies in the articles and from Web sites and reports from the National
      Cancer Institute, American Society of Clinical Oncology, and European
      Organization for Research and Treatment of Cancer. DATA SYNTHESIS: Progress in
      identifying the biochemical and molecular causes of cancer has led to discovery
      of abnormalities that characterize cancer cells and represent targets for
      development of drug therapies. TK receptors represent one such target when these
      are present in elevated quantities and/or aberrant forms. Abnormalities in these
      cell surface receptors have been correlated with development and progression of
      cancer, poor response to chemotherapeutic agents, and low survival rates. Several
      subtypes of TK receptors have been identified, and mutations in these have been
      associated with neoplasms of the breast, lung, colon, ovaries, and other organs.
      Approved agents, such as trastuzumab (Herceptin-Genentech) work by blocking a
      subtype of TK receptors that has been associated with breast cancer growth.
      Gefitinib (Iressa-AstraZeneca) was recently approved for treatment of non-small
      cell lung cancer in patients who have failed treatment with traditional
      chemotherapeutic agents. Other agents such as cetuximab, erlotinib, and
      canertinib are in advanced stages of clinical trials and may be available for
      general clinical use in the next few years. CONCLUSION: Cancer continues to be a
      difficult disease to treat, but newly identified cellular targets have resulted
      in new medications, and these promising agents are giving hope for additional
      options for patients with various solid tumors.

PMID- 14965155
TI  - Supplemental products used for weight loss.
AB  - OBJECTIVE: To review the scientific literature on several dietary supplements and
      herbal products commonly promoted for weight loss. DATA SOURCES: Recently
      published articles and abstracts identified through PubMed (May 1987-May 2003),
      MEDLINE (January 1966-May 2003), International Pharmaceutical Abstracts (January
      1970-May 2003), and Natural Medicines Comprehensive Database (January 1995-May
      2003) using the search terms supplement, herbal, weight loss, obesity,
      overweight, conjugated linoleic acid, ephedra, ephedrine, chromium, Garcinia
      cambogia, hydroxycitric acid, chitosan, and pyruvate. STUDY SELECTION: Performed
      manually by the authors. DATA EXTRACTION: Performed manually by the authors. Only
      single-agent, randomized, blinded, controlled studies with sufficient scientific
      rigor in overweight or obese subjects were included. DATA SYNTHESIS:
      Approximately 50 individual supplemental products and hundreds of combination
      products are promoted for weight loss. As a result, much confusion exists among
      health care professionals regarding the efficacy and safety of these products.
      Results for conjugated linoleic acid were positive in three clinical studies,
      with few adverse effects. Ephedra has been shown to be effective in promoting
      weight loss, especially when combined with caffeine, but it has a high adverse
      effect risk profile. The data regarding ephedra and ephedra combinations are
      conflicting, and many of the studies were poorly designed. Garcinia and chitosan
      have not shown much promise for weight loss, but little research has been done.
      Pyruvate has consistently shown positive weight loss effects. CONCLUSION:
      Overall, herbal products and dietary supplements promoted for weight loss lack
      sufficient supporting efficacy and safety data. More research is needed to draw
      definitive conclusions. Conjugated linoleic acid and pyruvate have the best
      supporting evidence, but larger and better-controlled trials are needed before
      pharmacists should recommend these agents to patients seeking to lose weight.

PMID- 14965156
TI  - Medicaid drug utilization review annual reports for federal fiscal year 1999:
      looking back to move forward.
AB  - OBJECTIVE: To review states' Medicaid drug utilization (DUR) annual reports for
      federal fiscal year (FFY) 1999 to assess the usefulness of the information
      provided in assisting states in improving their DUR programs. DATA SOURCES:
      Medicaid DUR annual reports from 43 states and the District of Columbia. DATA
      EXTRACTION: Five DUR experts conducted in-depth reviews of the annual reports to
      determine whether states provided the information required by the Health Care
      Financing Administration (HCFA; now the Centers for Medicare & Medicaid Services)
      annual report instructions, to assess the usefulness of information provided by
      states to other states seeking to improve their programs, and to consider what
      changes in report content are needed to increase the value of the reports. DATA
      SYNTHESIS: States provided the information requested by HCFA, but such
      information was not particularly useful in helping other states improve their
      programs, nor was it easily available to other states. These reports need to be
      reoriented. Rather than instruments useful for compliance monitoring, the reports
      should be remade as tools useful for educating DUR program staff. To do this,
      changes in report content are needed, and individual states should have access to
      reports from all states. Specific recommendations made based on these findings
      would be important first steps in improving the effectiveness of DUR programs.
      CONCLUSION: Much room for improvement remains in the content and distribution of
      Medicaid DUR annual reports. Finding ways to improve the effectiveness of DUR is
      especially important as the nation moves to implement a Medicare prescription
      drug benefit.

PMID- 14965157
TI  - Adverse effect monitoring: opportunity for patient care and pharmacy practice.
AB  - OBJECTIVES: To present an adverse effect monitoring tool with theoretical,
      practical, and data-supported explanation and justification for use in pharmacy
      practice for the purpose of building patient-pharmacist partnerships and
      improving medication-management outcomes. DESIGN: Randomized pretest-posttest
      experimental design. SETTING: Ambulatory patients in three multidisciplinary
      cancer clinics. PATIENTS: 74 patients who were beginning chemotherapy.
      INTERVENTIONS: A calendar for daily adverse drug event tracking by ambulatory
      patients was adapted from The WriteTrack: Personal Health Tracker and provided to
      those assigned to the intervention group, who were asked to record symptoms and
      possible adverse drug events during their first two chemotherapy cycles. Patient
      reports of self-monitoring activities were gathered through posttests (n = 74)
      and semistructured interviews (n = 7). MAIN OUTCOME MEASURES: Self-reported use
      and perceived usefulness of the tool. RESULTS: A total of 88.4% of the
      experimental group (38 of 43 individuals) reported using the monitoring tool to
      keep written track of adverse effects, while 38.7% of the control group (12 of 31
      individuals) reported keeping some form of written record of their experiences. A
      total of 65.8% of those in the intervention group found patterns in their adverse
      effects, 47.4% indicated they took the calendar to the clinic to help them recall
      events, and 26.3% reported using the calendar at the clinic to show their health
      care team what was happening. Experimental group subjects most often shared the
      adverse effect monitoring information with nurses alone (23.7%). Patients using
      the diary indicated that it had a high degree of utility and value and that they
      would use it again and recommend it to other patients with cancer. CONCLUSION: A
      system for adverse effect monitoring by patients in the context of cancer drug
      management was acceptable and useful, and pharmacists could incorporate this tool
      into their daily practice with minimal effort, time, and expense. Patients' self
      documented symptoms and adverse effects can be valuable data when used to help
      tailor medication regimens to improve clinical status while satisfying patients'
      personal priorities.

PMID- 14965158
TI  - Enhancing pharmacists' recommendation process in an internal medicine resident
      clinic.
AB  - OBJECTIVE: To determine the number and type of recommendations made by
      pharmacists in an internal medicine residency clinic, the percentage of
      recommendations that were addressed and acted upon by the residents, whether
      changes needed to be made to the recommendation process, and areas in which
      pharmacy services could be improved. SETTING: Outpatient, urban, internal
      medicine clinic. PRACTICE DESCRIPTION: The clinic operates Monday through
      Thursday afternoons. Each of these afternoons, six to eight medical residents
      evaluate patients. Pharmacists provide services on Monday and Thursdays. The
      pharmacists spend the mornings before patients' visits reviewing charts and
      making recommendations for more appropriate medication use. Originally,
      pharmacists' recommendations were listed on a form that was attached to the front
      of each patient's chart but did not become a part of the medical record. At
      times, pharmacists made recommendations while a medical resident presented the
      patient's case to the attending physician. PRACTICE INNOVATION: Data for calendar
      year 2002 were analyzed retrospectively to identify a recommendation acceptance
      rate, areas of potential improvement, and actions that might enhance pharmacists'
      effectiveness. MAIN OUTCOME MEASURES: Number of recommendations made, number of
      each type of recommendation made, percentage of overall recommendations addressed
      and acted upon by the residents, and percentage of each type of recommendation
      addressed and acted upon by the resident physician. RESULTS: For 61 patients, 135
      recommendations were made by pharmacists during 2002. Of these, 72 (53.3%) were
      therapeutic interventions and 63 (46.7%) were recommendations for laboratory
      monitoring. Overall, 66 (49.0%) recommendations were addressed and acted upon by
      the residents, while 69 (51.1%) were not addressed by the residents. Because of
      deficiencies identified in the communication process, a new form was developed
      that includes spaces for pharmacists' recommendations and residents' responses.
      Other potential future enhancements include providing more education for
      residents and implementing a pharmacist-run disease clinic. CONCLUSION: This
      retrospective analysis showed that pharmacists were able to identify many
      therapeutic and laboratory interventions, thus serving a useful role in patient
      care and physician education in an internal medicine residency clinic.

PMID- 14965159
TI  - Cancer awareness and prevention activities: assessment of pharmacists' knowledge
      and interest.

PMID- 14965160
TI  - Rufus Ashley Lyman (1876-1957): a towering figure in the field of pharmaceutical
      education.

PMID- 14965161
TI  - Resources for safe over-the-counter medication use.

PMID- 14965162
TI  - Control of T cell responses, tolerance and autoimmunity by regulatory T cells:
      current concepts.
AB  - Regulatory T cells have emerged as an important mechanism of regulating tolerance
      and T cell responses. CD4+ regulatory T cells can be divided into two main
      groups, natural regulatory T cells, which express high levels of CD25 on their
      cell surface and phenotypically diverse adaptive (antigen induced) regulatory T
      cells. Natural regulatory T cells are made in the thymus, and require strong
      costimulatory signals for induction and maintenance, express a transcription
      factor called Foxp3, and function by a largely unknown mechanism. Adaptive
      (antigen induced) regulatory T cells are made by sub-optimal antigenic signals in
      the periphery, in the presence of immunosuppressive cytokines, often in special
      circumstances, such as chronic viral infections or after mucosal administration
      of antigen, and rely on cytokines such as IL-10 and TGF-beta for suppression.
      Regulatory T cells offer a great potential for the treatment of autoimmune
      diseases and during transplantation.

PMID- 14965163
TI  - Chromium (III) produces distinct type of cell death in cultured cells.
AB  - Chromium acetate hydroxide is a chemical form of trivalent chromium (Cr III)
      originating from industrial processes. Although considered relatively nontoxic,
      upon longer treatment intervals it may cause irreversible cellular damage
      culminating in cell death. In our present work we have attempted to analyze some
      of the mechanisms whereby this chemical inflicts damage while focusing on the
      final observed endpoints. We report that 1 mM chromium acetate hydroxide is
      during weeks lasting treatment capable of injuring the plasma membrane of Hep-2
      cells, which in turn becomes permeable to Cr (III) ions. Analyses of several
      markers of cellular damage; i.e. mitochondrial activity, nuclear integrity and
      oxidative stress have shown that tested compound interacts directly with
      subcellular organelles and upon tested concentration and time induces distinct
      type of cell death bearing features of apoptosis and necrosis.

PMID- 14965164
TI  - Inhibition of aromatic amino acid decarboxylase by a group of new potential
      nonsteroidal anti-inflammatory drugs with antileukotrienic effects.
AB  - Possible in vitro inhibition of aromatic amino acid decarboxylase (AAD, EC
      4.1.1.28) by a group of phenylsulfonylbenzoic acid derivatives VUFB 19363, 19369,
      19370, 19371, and 19760 as new potential anti-inflammatory compounds was studied
      using the substrate L-tyrosine. Enzyme inhibition by 2.7 x 10(-5) M concentration
      of compound VUFB 19363 (Quinlukast) was 17%, AAD inhibition at 3.75 x 10(-5) M
      concentration of compounds VUFB 19369, 19370, 19371, and 19760 ranged between 9
      23%. There were distinct differences between individual compounds. Evaluation of
      inhibition kinetics suggested full reversibility with VUFB 19369 and the
      uncompetitive type of inhibition in the case of compound VUFB 19363. Considering
      the anti-inflammatory activity of the compounds studied, the weak AAD inhibition
      found is rather favourable for their prospective pharmacological effect.

PMID- 14965165
TI  - Effects of two types of restraint stress on the learned behaviour in rats.
AB  - To study the effects of stress on cognitive functions, Wistar and Lewis rats were
      exposed to restraint (immobilization stressor) (IMO) or restraint combined with
      partial immersion into water (IMO+C). Learned discriminatory avoidance response
      in Y-maze, with foot-shock as an unconditioned stimulus, was used as a memory
      test. The latency to enter the correct arm and number of wrong entries were daily
      recorded during the training period (20 days) until the criterion was reached,
      which was set at 90% avoidances (choosing the correct arm). After exposure of
      rats to one of the stressors for 60 min, the rats were returned to the home cage;
      the latency to enter the safe arm was recorded in 6 daily trials that started 1 h
      after application of stressor. Both stressors significantly prolonged the
      avoidance latencies for 2 or 3 days in Wistar and Lewis rats, respectively; then
      the latencies returned to the values obtained before the stress exposure. In
      Lewis rats, the latencies more increased after IMO+C than after IMO stressor, and
      the maximal increase in latencies was higher in Lewis rats than in Wistar rats.
      The latency did not reach the time limit for foot-shock delivery, and the number
      of correct choices remained unchanged in both strains. The results indicate that
      the used restraint stressors did not affect the long-term memory; rather a
      transient impairment of retrieval can be considered. Further, differences in
      response of Lewis and Wistar rats may be interpreted by different activity of
      hypothalamic-pituitary-adrenal axis activity in used strains.

PMID- 14965166
TI  - Inhalation apparatus for generating sarin and soman toxic vapors.
AB  - The developed inhalation system is a dynamic and whole-body exposure model
      designated for generating sarin or soman vapors. It consists of an evaporating
      apparatus, an inhalation chamber and a carbon filter. The inhalation chamber is
      made of stainless steel and its total volume is 36 l. The concentration of
      organophosphorus compound depends on airflow through the chamber, syringe volume
      of the dosing pump and dosing speed. For determination of organophosphorus
      compound (OPC) concentration, a modification of Ellman method is used. At
      generating of vapors in the inhalation chamber the means of the yield were 61.4
      +/- 6.6% for sarin and 35.8 +/- 3.5% for soman. The better yield for sarin than
      for soman, because of the higher volatility of sarin in comparison with soman was
      achieved. The stable concentration of the OPC for several hours could be
      maintained in the inhalation chamber when only relatively small amount of the OPC
      is used. Using the developed inhalation system LCt50 for sarin and for soman in
      rats was determined. At 1 h exposure the LCt50 values were 4.72 mg x h(-1) x m(
      3) for sarin and 4.81 mg x h(-1) x m(-3) for soman. The results presented show
      that the inhalation chamber successfully fulfils the role of instrument for
      inhalation intoxication of small laboratory animals with highly toxic OPC.

PMID- 14965167
TI  - A study of potential toxic effects after repeated 10-week administration of a new
      iron chelator--salicylaldehyde isonicotinoyl hydrazone (SIH) to rabbits.
AB  - Salicylaldehyde Isonicotinoyl Hydrazone (SIH)--a Pyridoxal Isonicotinoyl
      Hydrazone (PIH) analogue--is an effective iron chelator with antioxidant and
      antimalarial effects, as documented in numerous in vitro studies. However, no
      toxicological data obtained from in vivo studies have been made available yet. In
      this study, the potential toxic effects of repeated administration of SIH (50
      mg/kg, once weekly, 10 weeks, i.p.), partially dissolved in a 10% Cremophor
      solution, on various biochemical, haematological, and cardiovascular parameters
      and on morphology of selected tissues were investigated in rabbits. The obtained
      values were compared with data from the control (saline, 1 ml/kg, i.v.) and the
      Cremophor (10% Cremophor solution, 2 ml/kg, i.p.) groups. In this study, SIH did
      not induced marked signs of toxicity: No premature deaths occurred, the body
      weight increase was comparable with the control and Cremophor groups. Only few
      and mild changes in some biochemical and haematological parameters could be
      determined, most of them were noticed also in the control or Cremophor groups.
      The morphological changes in the kidney were mild and did not manifest in the
      biochemical examination. The cardiac function was also not affected markedly--the
      values of left ventricular ejection fraction and systolic time interval did not
      differ from the values of control group. Only an increased left ventricular
      contractility (dP/dtmax) was noticed in the SIH group at the end of the
      experiment as compared to the controls (13,354+/-1191 vs. 9339+/-647 mmHg/s,
      resp.). These results seem to be promising from the standpoint of possible
      clinical use of SIH.

PMID- 14965168
TI  - Cardiac troponins following repeated administration of an iron chelator-
      salicylaldehyde isonicotinoyl hydrazone (SIH)--in rabbits.
AB  - Both cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are considered to be
      reliable biomarkers with sufficient sensitivity and specificity for cardiac
      injury in the majority of laboratory animals. The aim of our study was to compare
      the diagnostic performance of cTnT and cTnI in three groups of rabbits: 1)
      control (saline 1 ml/kg i.v.); 2) Salicylaldehyde Isonicotinoyl Hydrazone--SIH
      (50 mg/kg, once weekly, i.p.; partially dissolved in 10% Cremophor solution); 3)
      10% Cremophor solution in water (2 ml/kg i.v.). The drugs were given once a week,
      10 administrations. The concentration of cTnT was measured using Elecsys Troponin
      T STAT Immunoassay (Roche). The concentration of cTnI was measured using AxSYM
      Troponin I (Abbott). The linear regression model was applied to see if there is a
      dependence between cTnT and cTnI. The coefficient of determination was not
      acceptable in all groups. The highest value of R2 was found in the control group
      (R2 = 0.424). We may conclude that in rabbits meaningful dependence between cTnT
      and cTnI was not found. According to our long-term experiences cTnT seems to be
      more suitable cardiomarker in rabbits in comparison with cTnI where the data are
      characterized by the large scatter.

PMID- 14965169
TI  - Hairy cell leukemia: an autopsy study.
AB  - Autopsy study from 21 patients with hairy cell leukemia was performed. All
      patients had the expected widespread involvement of the hematopoietic system.
      Leukemic infiltration of lymph nodes was detected in 12 cases. Liver involvement
      was present in 19 patients, leukemic infiltration ranged from focal portal and
      sinusoidal infiltration to massive infiltration that effaced the hepatic
      architecture. Twelve patients showed leukemic infiltration of the spleen,
      remaining 9 patients underwent previous splenectomy for massive splenomegaly. We
      also found leukemic infiltration of kidneys in four cases, two patients showed
      leukemic involvement of the lungs. The cause of death was related to impaired
      immunity (sepsis, bronchopneumonia, etc.) in the majority (73%) of cases.

PMID- 14965170
TI  - Prevalence of CD8/CD4 ratio in the fetal thymic parenchyme in Down's syndrome.
AB  - AIM: The maturation of most T-lymphocyte precursors takes place within the
      meshwork of thymic epithelial cells. Different steps of this process can be
      defined by immunologic phenotyping. The prothymocytes are positive for the
      terminal deoxynucleotidyl transferase (TdT) and give rise to cortical thymocytes,
      which express CD1, CD2, CD3, CD5, and both CD4 and CD8. These CD4 and CD8 double
      positive cortical thymocytes differentiate into two lineages: CD4+ or CD8+
      lymphocytes of the thymic medulla, by the tenth week of gestation. Our study
      points towards the determination of the CD8 cytotoxic/suppressor capacity of the
      fetal thymus in Down's syndrome. EXPERIMENTAL DESIGN: A quantitative comparison
      of T-lymphocytes (CD3, CD4, and CD8) in the thymic parenchyme in embryos after
      voluntary abortion during 2nd trimester of gestation and embryos with Down's
      syndrome, respectively, was performed. RESULTS: Our results showed: 1) A
      statistically significant depletion in the total number of T-cells (CD3 positive)
      in the cases of embryos with Down's syndrome over those after voluntary abortion,
      during the second trimester of gestation (p<0.0001, t-test). 2) A significant
      difference in the CD8/CD4 ratio in the cases of embryos with Down's syndrome,
      during the second trimester of gestation which was numerically stronger with the
      progress of fetal development (20th week: p<0.025; 24th week: p<0.01, chi
      square). CONCLUSIONS: The occurrence of increased CD8/CD4 ratio in the cases with
      Down's syndrome, in the second trimester of gestation, underlines the
      cytotoxic/suppressor property of the thymus in the affected fetuses.

PMID- 14965171
TI  - Platelets activation in patients undergoing PTCA and their responsiveness after
      in vitro stimulation.
AB  - We evaluated expression of platelet activation markers in blood samples of 15
      patients who underwent percutaneous transluminal coronary angioplasty (PTCA) by
      flow cytometry. Analysis was performed before the beginning of PTCA, during
      initial coronary angiography and after the end of PTCA or after a stent
      placement, respectively. We evaluated platelet-derived microparticles, platelet
      leukocyte aggregates, platelet aggregates and a membrane expression of CD62P and
      CD63 molecules. Responsiveness of platelets to the activation in vitro with
      thrombin-receptor activating protein-6 (TRAP-6) was tested simultaneously.
      Statistically significant differences between patient samples were found only in
      the expression of the activation markers CD62P (before PTCA 0.22%, during 0.39%,
      after 0.67%), CD63 (0.26%/0.45%/0.85%) and platelet-leukocyte aggregates
      (13.57%/18.39%/23.63%). In the same group the expression of all constitutive
      membrane markers was statistically significantly decreased: in patients
      undergoing PTCA was the expression of CD9: 87.98% (in comparison with control
      group 94.98%), CD31: 87.10% (92.78%), CD36: 87.37% (90.98%), CD41: 88.09%
      (95.62%), CD42a: 88.54% (94.98%), CD42a: 88.31% (94.13%).

PMID- 14965172
TI  - Changes of visual function and visual ability in daily life following cataract
      surgery.
AB  - PURPOSE: To examine best corrected visual acuity (BCVA), contrast sensitivity
      (CS) and functional visual complaints in early cataract and after the cataract
      surgery. PATIENTS AND METHODS: 53 eyes with early cataract (BCVA 20/30: Snellen
      charts) were examined before the surgery as well as 12 months after the surgery.
      BCVA was tested using logMAR chart. CS was examined using VCTS chart in 6 spatial
      frequencies. Influence of glare was tested using BAT. Patients' subjective visual
      functions were evaluted using a questionnaire (distance vision, near vision,
      mesopic vision and glare conditions). 22 subjects were examined as control group.
      RESULTS: BCVA was 0.52 (0.22-1.05) preoperatively and 0.83 (0.37-1.26)
      postoperatively. BCVA in patients in both terms was significantly lower compared
      to the control group. CS in patients before surgery was significantly lower
      compared to controls, postoperatively improved significantly and was only
      nonsignificantly lower compared to controls except for the highest spatial
      frequency. Glare had only nonsignificant influence. The questionnaire scores were
      correlated with visual performance in both terms. CONCLUSIONS: The significant
      improvement of both BCVA and CS suggest that cataract surgery improves quality of
      life in early cataract. Questionnaire should be considered as adjuncts to BCVA
      and CS in evaluating early cataract.

PMID- 14965173
TI  - Clinical assessment of 324 breast cancer cases in two centers between the years
      of 1992 and 2002.
AB  - The records of the 324 patients with breast cancer; diagnosed and followed in two
      different University Hospital between years of January 1992 and January 2002 were
      reviewed retrospectively. The median age of the patients was 49.0+/-12.5 years,
      with the range of 18 and 90 years. The most frequently seen age interval of the
      patients was 40 and 49 years. The most frequently seen symptom and physical
      examination finding of the patients were breast mass. Breast cancer was diagnosed
      in 324 women, 173 in the left breast and 151 in the right breast. At the hospital
      admission percentages of the patients' disease stages were as follows: I (2.8%),
      IIA (30.0%), IIB (24.0%), IIIA (19.8%), IIIB (11.4) and IV (12.0%). The most
      frequently seen histopathological diagnosis was infiltrative ductal carcinoma
      (84.4%). Axillary lymph node metastasis was found in 61.7% of the patients.
      Primary therapeutic options and percentages were surgical therapy (78.5%),
      systemic chemotherapy (17.5%) and radiotherapy (4%). Systemic chemotherapy was
      given to 81.2% of the patients. From the files, estrogen receptor status was
      known in 311 and positive in 128 (41.2%) of them. Tamoxifen was given patients
      who had positive estrogen receptor. The five-year survival rate of the patients
      was calculated as 75.9%.

PMID- 14965174
TI  - An increased frequency of carpal tunnel syndrome in sarcoidosis. Results of a
      study based on nerve conduction study.
AB  - Sarcoidosis is a systemic disease which affects the musculoskeletal system;
      however, its association with carpal tunnel syndrome (CTS) has been reported only
      rarely. In our study, we tried to determine the prevalence of CTS in our
      consecutive sarcoidosis patients based on their symptoms and nerve conduction
      study (NCS). Fifty-six patients (mean age: 45.2) who were followed up with the
      diagnosis of sarcoidosis at our center and who gave informed consent for NCS were
      included into the study. The patients were questionned for the presence of hand
      symptoms: paresthesia, pain, nocturnal paresthesia and/or pain, and, they
      underwent NCS. Ten (17.9%) patients had recurrent paresthesia, 12 (21.4%) had
      pain, and 8 (14.3%) had nocturnal paresthesia and/or pain. The results of NCS
      showed that 41% of the patients had findings compatible with CTS. Extrapulmonary
      involvement was significantly more frequent in these patients when compared to
      patients without CTS (p=0.04). Also, patients with CTS were older than the others
      and CTS-associated symptoms were more frequent in them although this was not
      significant (p>0.05). In this study, by performing NCS we detected quite a high
      prevalence of CTS in our sarcoidosis patients. The fact that most of the patients
      were asymptomatic was interesting.

PMID- 14965175
TI  - Two ways of immediate rehabilitation of edentulous mandible with dental implants
      and prostheses--critical view on Branemark System Novum.
AB  - With appropriate stabilization and occlusal loading, mandibular implants can be
      immediately loaded in a complete-arch configuration with no apparent detrimental
      effect on the rates of osseointegration. Ten patients were treated with the
      immediate loading protocols in completely edentulous mandible either with
      conventional one-stage implants and a provisional denture or with the Branemark
      System Novum and a definite restoration. A total of 42 implants were placed. One
      Novum implant was lost 1 month after placement. The clinical success rate of the
      immediately loaded implants at the time of the 6-month check-up was 97.6%.
      Radiographic surveys completed by panoramic radiographs 6 months after the
      surgery revealed good healing of bone at implant interface. After the period,
      mean marginal bone loss was 0.4 mm (ranged from 0 mm to 1.5 mm). The results of
      this short-term clinical and radiographic study indicate that the precise
      surgical and prosthetic protocol allows successful prosthetic rehabilitation of
      mandibular edentulism and that the provisional or permanent fixed reconstruction
      can be provided to a patient on a day of fixture surgery. Finally, authors
      consider critical comments on Branemark System Novum.

PMID- 14965176
TI  - Primary non-Hodgkin lymphoma of skeletal muscle coexistence with cutaneous
      infiltration.
AB  - This report describes a non-Hodgkin lyphoma case presenting with skeletal muscle
      and cutaneous involvement. A 75 year-old man was admitted to hospital with mass
      in the right upper extremity and skin lesions on the back of his trunk.
      Excisional mass biopsy was reported immunohistopthologically as large B-cell
      lymphoma. Primary extranodal lymphoma arising from skeletal muscle and
      concomitant skin infiltration of other body localization is not common. So this
      case was represented and relevant literature was reviewed.

PMID- 14965177
TI  - Response to gefitinib in pericardial effusion due to lung cancer.
AB  - We described a 70 years old patient with pericardial effusion due to
      adenocarcinoma of the lung, in whom gefitinib, which is an oral selective
      inhibitor of the epidermal growth factor receptor of tyrosine kinase,
      demonstrated a marked antitumor effect. We recommend possible consideration of a
      treatment with gefitinib for female patients with pericarditis carcinomatosa due
      to lung adenocarcinoma, even if they have a poor performance status and are not
      indicated for other intensive therapy.

PMID- 14965178
TI  - Practical protocols for the prevention of dental disease in community settings
      for people with special needs: preface.
AB  - This issue of Special Care in Dentistry presents protocols that were designed
      during a conference, Practical Protocols for the Prevention of Dental Disease in
      Community Settings for People with Special Needs, which was held at the
      University of the Pacific School of Dentistry on February 1, 2002. After each
      expert reviewed and reported on one area of the literature, which included risk
      assessment; chlorhexidine mouth rinses; xylitol chewing gum; topical fluoride and
      fluoride varnish applications; and methods to control or treat periodontal
      disease, practical protocols were developed. Next, a strategy of implementation
      and dissemination will be designed using nurses, case managers, social workers,
      caregivers, and others to encourage people with special needs to use these
      protocols. A plan will also be implemented to increase social and health care
      provider awareness about these interventions through professional publications
      and educational opportunities. The goal is to reduce dental disease in special
      needs populations and thereby decrease the need for difficult and costly
      treatment.

PMID- 14965179
TI  - Practical protocols for the prevention of dental disease in community settings
      for people with special needs: the protocols.
AB  - People with special needs have more dental disease and more missing teeth than
      the general population. They also have reduced access to oral health diagnostic,
      preventive, interceptive and treatment services. If services are available, they
      can be complicated and costly. It is critical to prevent dental diseases in these
      individuals. This article presents a set of practical protocols for preventing
      dental disease in people with special needs. These protocols are designed to be
      used in community settings outside of a dental office.

PMID- 14965180
TI  - Preventing dental disease for people with special needs: the need for practical
      preventive protocols for use in community settings.
AB  - People with disabilities have more dental disease, more missing teeth, and more
      difficulty receiving dental care than other members of the general population.
      Because of the deinstitutionalization movement during the later 20th century,
      many formerly institutionalized people now reside in community settings, which
      lack oral health services. Even individuals who were not institutionalized have
      barriers to oral health services. These realities underscore the importance of
      preventing dental disease in people with special needs by establishing preventive
      dental disease protocols.

PMID- 14965181
TI  - Making clinical decisions for dental care: concepts to consider.
AB  - Clinical decisions are often made with incomplete information, yet patient care
      decisions are made every day. Patients vary clinically, uncertainty exists in
      diagnostic and prognostic information, and many preventive and treatment
      alternatives have not been formally assessed for their effectiveness. Because
      scientific information will never answer all clinical questions, clinical
      decisions are partially based on probabilistic information. This paper describes
      how to apply clinical decision making to diagnosing and managing dental caries
      and periodontal diseases. By using explicit information to quantify probabilities
      and outcomes, clinical decision making analyzes decisions made under uncertain
      conditions and the uncertain impact of clinical information. Clinical decision
      making incorporates concepts for preventing, diagnosing and treating dental
      caries and periodontal diseases: risk assessment, evidence-based dentistry, and
      multiple oral health outcomes. This information can serve as a tool for
      clinicians to augment clinical judgment and expertise.

PMID- 14965182
TI  - Chlorhexidine and xylitol gum in caries prevention.
AB  - This paper presents the current best evidence on the respective and comparative
      outcomes of chlorhexidine and xylitol and extrapolates these data to individuals
      with special needs. It analyzes the probable mechanisms of action for both
      chlorhexidine and xylitol then reviews individual products and discusses the
      anticipated effectiveness of these products in individuals with special needs.

PMID- 14965183
TI  - The use of topical fluoride to prevent or reverse dental caries.
AB  - Topical fluoride has been the main stay of caries prevention for many decades.
      There are several mechanisms which make it beneficial including inhibiting
      demineralization, enhancing remineralization, and inhibiting bacterial growth.
      Topical fluoride is available in many different forms. The concentrations of
      various fluoride preparations range from 225 parts per million (ppm) fluoride in
      over-the-counter oral rinses to 22,600 ppm in the fluoride varnishes. The
      clinician must decide which type of topical preparation is best suited for their
      patient. Patients with high caries risk may benefit from prescription strength
      fluorides (along with the other chemical and dietary therapies described in this
      issue of Special Care in Dentistry). The application of fluoride varnish is an
      excellent topical form for those patients who have access to dental care and for
      whom it is difficult to comply with the use of other topical forms.

PMID- 14965184
TI  - Fluoride varnish for caries prevention: comparisons with other preventive agents
      and recommendations for a community-based protocol.
AB  - This paper reviews fluoride varnish (FV) literature to develop a community-based
      protocol for people with special needs or those who are caries susceptible.
      Safety, personnel and cost issues are discussed and existing NIH, CDC and WHO
      recommendations are presented. FV studies are assessed with respect to type of FV
      to use and frequency of application. FV is compared with studies using other
      caries preventive agents: 0.2% NaF mouthrinse, acidulated phosphate fluoride
      (APF) gel, dental sealants, water fluoridation and chlorhexidine. Because there
      are few FV studies among special need populations, conclusions are based on
      available literature and public health principles. If personnel are available, FV
      use is preferred to APF gel and may be preferable to 0.2% NaF mouthrinse. FV is
      more effective in optimally fluoridated communities. If many occlusal surfaces
      are at risk, sealants should be applied. Additional combinations and frequencies
      of preventive agents should be tested, especially for people with special needs
      and high caries risk adults.

PMID- 14965185
TI  - Using community-based protocols to prevent dental disease in people with special
      needs: periodontal prevention and intervention.
AB  - This paper discusses preventing and treating periodontal diseases in people with
      special needs.

PMID- 14965186
TI  - Bicycle shock absorption systems and energy expended by the cyclist.
AB  - Bicycle suspension systems have been designed to improve bicycle comfort and
      handling by dissipating terrain-induced energy. However, they may also dissipate
      the cyclist's energy through small oscillatory movements, often termed 'bobbing',
      that are generated by the pedalling movements. This phenomenon is a major concern
      for competitive cyclists engaged in events where most of the time is spent
      climbing, e.g. off-road cross-country races. An acceptable method to assess the
      overall efficacy of suspension systems would be to evaluate energy consumed by
      cyclists using different types of suspension systems. It could be assumed that
      any system that reduces metabolic expenditure for the cyclist would automatically
      lead to performance improvement. Unfortunately, only a limited number of studies
      have been conducted on that subject. Moreover, the conclusions that can be drawn
      from most of them are limited due to unsatisfactory statistical power,
      experimental protocols, measuring techniques and equipment. This review presents
      and discusses the most relevant results of studies that focused on mechanical
      simulations as well as on energy expenditure in relation to off-road bicycle
      suspension systems. Evidence in the literature suggests that cyclist-generated
      power that is dissipated by suspensions is minimal and probably negligible on
      most terrains. However, the scarce studies on the topic as well as the
      limitations in the conclusions that can be drawn from most of them indicate that
      we should remain cautious before supporting the use of dual suspension bicycles
      on all course types and for all cyclists. For example, it should be kept in mind
      that most cross-country racers still use front suspension bicycles. This might be
      explained by excessive cyclist-generated power dissipation at the high mechanical
      powers developed by elite cross-country cyclists that have not been studied in
      the literature. Finally, suspended bicycles are more comfortable. Moreover, the
      fact that suspension systems may significantly reduce physical stress should not
      be overlooked, especially in very long events and for recreational cyclists.

PMID- 14965187
TI  - Growth hormone and exercise tolerance in patients with cystic fibrosis.
AB  - Cystic fibrosis (CF) is a life-limiting inherited disorder characterised by
      pulmonary disease, pancreatic dysfunction and symptoms of malnutrition that are
      all interrelated with low exercise capacity and poor survival rate. Therapy with
      growth hormone (GH) may improve the reduced dimensional and functional capacity
      associated with poor nutritional status and catabolism and therefore improve
      exercise tolerance, quality of life and survival rate in patients with CF. The
      literature about GH treatment and its effect on exercise tolerance are rather
      limited, not always consistent and methodological concerns restrict further
      analysis. GH treatment may have beneficial effects on both growth and exercise
      tolerance without serious complications in prepubertal children with CF. The
      observed dimensional changes of the muscular, cardiovascular and pulmonary system
      seem to improve aerobic exercise capacity and respiratory and peripheral muscle
      strength. The physiological background of the observed changes is not yet fully
      understood, therefore, larger-scale studies with an optimised design are
      required.

PMID- 14965188
TI  - 5' adenosine monophosphate-activated protein kinase, metabolism and exercise.
AB  - The 5' adenosine monophosphate-activated protein kinase (AMPK) is a member of a
      metabolite-sensing protein kinase family that functions as a metabolic 'fuel
      gauge' in skeletal muscle. AMPK is a ubiquitous heterotrimeric protein,
      consisting of an alpha catalytic, and beta and gamma regulatory subunits that
      exist in multiple isoforms and are all required for full enzymatic activity.
      During exercise, AMPK becomes activated in skeletal muscle in response to changes
      in cellular energy status (e.g. increased adenosine monophosphate [AMP]/adenosine
      triphosphate [ATP] and creatine/phosphocreatine ratios) in an intensity-dependent
      manner, and serves to inhibit ATP-consuming pathways, and activate pathways
      involved in carbohydrate and fatty-acid metabolism to restore ATP levels. Recent
      evidence shows that although AMPK plays this key metabolic role during acute
      bouts of exercise, it is also an important component of the adaptive response of
      skeletal muscles to endurance exercise training because of its ability to alter
      muscle fuel reserves and expression of several exercise-responsive genes. This
      review discusses the putative roles of AMPK in acute and chronic exercise
      responses, and suggests avenues for future AMPK research in exercise physiology
      and biochemistry.

PMID- 14965189
TI  - Alterations of neuromuscular function after prolonged running, cycling and skiing
      exercises.
AB  - It is well known that impairment of performance resulting from muscle fatigue
      differs according to the types of contraction involved, the muscular groups
      tested and the exercise duration/intensity. Depending on these variables,
      strength loss with fatigue can originate from several sites from the motor cortex
      through to contractile elements. This has been termed 'task dependency of muscle
      fatigue'. Only recently have studies focused on the origin of muscle fatigue
      after prolonged exercise lasting 30 minutes to several hours. Central fatigue has
      been shown to contribute to muscle fatigue during long-distance running by using
      different methods such as the twitch interpolation technique, the ratio of the
      electromyogram (EMG) signal during maximal voluntary contraction normalised to
      the M-wave amplitude or the comparison of the forces achieved with voluntary- and
      electrically-evoked contractions. Some central activation deficit has also been
      observed for knee extensor muscles in cycling but central fatigue after
      activities inducing low muscular damage was attenuated compared with running.
      While supraspinal fatigue cannot be ruled out, it can be suggested that spinal
      adaptation, such as inhibition from type III and IV group afferents or
      disfacilitation from muscle spindles, contributes to the reduced neural drive
      after prolonged exercise. It has been shown that after a 30 km run, individuals
      with the greatest knee extensor muscle strength loss experienced a significant
      activation deficit. However, central fatigue alone cannot explain the entire
      strength loss after prolonged exercise. Alterations of neuromuscular propagation,
      excitation-contraction coupling failure and modifications of the intrinsic
      capability of force production may also be involved. Electrically-evoked
      contractions and associated EMG can help to characterise peripheral fatigue. The
      purpose of this review is to further examine the central and peripheral
      mechanisms contributing to strength loss after prolonged running, cycling and
      skiing exercises.

PMID- 14965191
TI  - Snowboarding injuries : current trends and future directions.
AB  - Snowboarding has become one of the premier alpine sports. The past decade has
      seen the popularity of snowboarding increase dramatically and the recent Winter
      Olympic Games at Salt Lake City, USA, showcased the strong visual appeal of the
      sport and the youth-oriented lifestyle and culture that accompanies it. The
      injury profile of the sport has also undergone change along with technological
      advances in boot and binding systems and the changing demographics of the sports
      participants. Central to the development of injury-prevention strategies is
      knowledge of the profile of injuries that occur, understanding those who are at
      particular risk and, if possible, the biomechanical factors involved in each
      injury type. Snowboarding was initially considered a dangerous, uncontrolled,
      alpine sport - an opinion based on little or no scientific evidence. That
      evidence has rapidly grown over the past decade and we now know that snowboard
      injury rates are no different to those in skiing; however, the injury profile is
      different. The purpose of this review is to give some perspective to the current
      snowboard injury literature. It discusses not only the demographic profile of
      those injured and the type of injuries that occur, but also gives some insight
      into the progress that has occurred in determining the impact of specific
      prevention strategies, such as splints to prevent injuries to the wrist/forearm.
      The next decade will also see a greater understanding of the biomechanical forces
      involved in snowboard injuries, which may well impact on future technological
      advances. As the literature indicates, however, some things will not change, e.g.
      injuries are more likely to occur in beginners and lessons need to be reinforced
      as a fundamental aspect of any injury-prevention strategy.

PMID- 14965190
TI  - Dyspnoea in health and obstructive pulmonary disease : the role of respiratory
      muscle function and training.
AB  - A consistent finding of recent research on respiratory muscle training (RMT) in
      healthy humans has been an attenuation of respiratory discomfort (dyspnoea)
      during exercise. We argue that the neurophysiology of dyspnoea can be explained
      in terms of Cambell's paradigm of length-tension inappropriateness. In the
      context of this paradigm, changes in the contractile properties of the
      respiratory muscles modify the intensity of dyspnoea predominantly by changing
      the required level of motor outflow to these respiratory muscles. Thus, factors
      that impair the contractile properties of the respiratory muscles (e.g. the
      pattern of tension development, functional weakening and fatigue) have the
      potential to increase the intensity of dyspnoea, while factors that improve the
      contractile properties of these respiratory muscles (e.g. RMT) have the potential
      to reduce the intensity of dyspnoea. In patients with obstructive pulmonary
      disease, functional weakening of the inspiratory muscles in response to dynamic
      lung hyperinflation appears to be a central component of dyspnoea. A decrease in
      the intensity of respiratory effort sensation (during exercise and loaded
      breathing) has been observed in both healthy individuals and patients with
      obstructive pulmonary disease after RMT. We conclude that RMT has the potential
      to reduce the severity of dyspnoea in healthy individuals and in patients with
      obstructive pulmonary disease, and that this probably occurs via a reduction in
      the level of motor outflow. Further work is required to clarify the role of RMT
      in the management of other disease conditions in which the function of the
      respiratory muscles is impaired, or the loads that they must overcome are
      elevated (e.g. cardiorespiratory and neuromuscular disorders).

PMID- 14965195
TI  - Update on sirolimus drug-eluting stents.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) has become the main method
      of coronary revascularization. However, despite technical advancement, restenosis
      with incidence rate of 30 to 50% remains a major limitation to the long-term
      success of PTCA. The introduction of stents has significantly improved capability
      of interventional cardiology in treatment and prevention of restenosis. Recent
      experimental studies in animals, clinical studies in humans and multi-center
      randomized clinical trials with Sirolimus-eluting stents, have demonstrated a
      significant reduction in vasculoproliferative response with no intimal tissue
      growth. Moreover, no significant adverse clinical events have been reported at
      long-term follow-up and first studies that explored the potential of this
      technology for the treatment of in-stent restenosis demonstrated safety and
      efficacy. Although the first clinical experiences with drug-eluting stents have
      produced stunning results, there are a number of theoretical limitations to these
      devices, including: 1) limitations of drug loading capacity and 2) ability to
      control drug elution that could result in unfavorable pharmacokinetics. There are
      also questions about the durability of the polymer coatings (deformation under
      mechanical stress, gaps between metal and arterial wall, etc). The thickness of
      some coatings makes them unsuitable for very small vessels. Finally most
      biodegradable coatings are prone to chronic inflammation. Since only a polymer
      coated bare metal stent remains following the drug's release, the potential for
      long term polymer biocompatibility problems remains a concern. The potential for
      some drugs to produce radiation-like effects such as "black holes", malapposed
      and naked struts and wall thinning are potentially the dark side of this
      technology and may contribute to late thrombosis, aneurysms or delayed
      restenosis. Long term clinical follow-up is necessary to assess the long term
      safety of this technology. There is a legitimate question as to whether drug
      eluting stents will produce similar results across all patient subsets
      encountered in "real-life" interventional practice (e.g. long lesions, small
      diameter vessels, vein grafts, chronic total occlusions, bifurcated and ostial
      lesions). Cost-benefit issues also need to be addressed, especially because
      multivessel stenting and multistent usage is likely to increase.

PMID- 14965196
TI  - Dexamethasone and restenosis after coronary stent implantation: new indication
      for an old drug?
AB  - Restenosis after stent implantation is mainly characterized by an inflammatory
      response to the procedural injury and an intense fibrocellular response including
      smooth muscle cell (SMC) proliferation. After angioplasty alone, the restenosis
      process also involves thrombus formation and negative remodeling. Due to the
      pleiotropic mode of action exerted by glucocorticoids which include profound anti
      inflammatory and immunosuppressive effects, direct inhibition on SMC
      proliferation and apoptosis, their potential in the prevention of restenosis has
      gained widespread interest. Over the last decade, preclinical and clinical data
      have not been able to conclusively document a robust therapeutic effect on
      restenosis after angioplasty or stent implantation. Only recently, preclinical
      data and limited observations in humans using drug eluting stents for local drug
      delivery have suggested beneficial effects of dexamethasone on neointimal
      proliferation. Randomized clinical trials using local drug delivery are expected
      to start in the near future. In the light of these ongoing developments, this
      review summarizes the pathophysiological basis of glucocorticoid action in the
      context of restenosis, provides an overview of the animal data available and
      discusses the clinical results that have been gathered over the last decade with
      particular emphasis on dexamethasone.

PMID- 14965197
TI  - Local drug delivery using coated stents: new developments and future
      perspectives.
AB  - Percutaneous coronary intervention has been hampered by restenosis since its
      inception. Many research projects including the use of various devices and
      systemic drug administration have shown disappointing results. The clinical data
      reported from trials with sirolimus- and paclitaxel- eluting stents have been
      very promising, such that stents with the capability of drug elution are
      currently attracting the medical community for the prevention of restenosis.
      Based on the mechanism of action of the drugs released from the stent and the
      target of the restenotic process, there may be 4 therapeutic objectives: anti
      inflammatory, anti-proliferative, anti-migratory, and pro-endothelial healing.
      There are many candidate agents for drug-eluting stents, however, it now becomes
      clear that not all drug-eluting stents are equally effective. This article
      describe candidate agents which have been tested or currently under
      investigation, and summarize the latest information.

PMID- 14965198
TI  - Insights into early and rapid effects of statin therapy after coronary
      interventions.
AB  - Recent trials provide a wealth of data documenting the benefit of cholesterol
      lowering therapy with statins in both primary and secondary prevention. A growing
      body of evidence indicates that statins possess pleiotropic effects - independent
      of, or at least in addition to their lipid-lowering capacity, including
      inhibition of smooth muscle cell proliferation and subsequently neointimal
      proliferation, platelet aggregation as well as antiinflammatory and direct
      beneficial effects on endothelial function. The current review summarizes recent
      findings in non-randomized and randomized trials assessing the efficacy of statin
      therapy following coronary interventions with or without stent implantation. It
      highlights the efficacy of statins in the settings of acute coronary syndromes.
      Current management of acute coronary syndromes requires early administration in
      combination with acute interventions. High risk patients which receive the
      greatest benefit could be identified by measuring serum markers such as
      preprocedural C-reactive protein levels. The present article also describes
      important novel actions of statins supporting the early initiation of statins
      post intervention, such as the stimulation of reendothelialization - a crucial
      step in the healing process of the vascular wall - which is mediated at least in
      part by mobilization of bone-marrow derived endothelial progenitor cells.

PMID- 14965199
TI  - Low-molecular weight heparins in percutaneous coronary interventions: current
      concepts, problems, and perspectives.
AB  - A growing body of evidence suggests that low molecular weight heparin (LMWH) is
      at least as effective as unfractionated heparin (UFH) in the medical management
      of acute coronary syndromes (ACS) including acute myocardial infarction. Several
      studies support an early invasive as compared to a conservative (non-invasive)
      approach utilizing percutaneous coronary intervention (PCI) in these patients.
      During coronary angiography and PCI systemic anticoagulation usually
      administering UFH should prevent thrombus formation at the catheter equipment and
      at the site of vessel injury. The widespread use of UFH as the anticoagulant of
      choice is explained by low costs, easy reversibility and accepted anticoagulant
      properties. However, the clinical support for the use of UFH in PCI is largely
      based on retrospective and observational data only. Compared to UFH, LMWH have
      distinct pharmacological advantages, including ease of administration and usually
      no need for monitoring. A major drawback of LMWH is the predominant renal
      clearance which may lead to unpredictable levels of anticoagulation in patients
      with impaired renal function. Since LMWH constitute an extremely heterogeneous
      group of drugs each LMWH should be recognized as an individual pharmaceutical
      compound. Consequently, pharmacodynamic and pharmacokinetic properties of one
      LMWH must not be extrapolated for other LMWH. A growing body of evidence supports
      the use of LMWH in ACS, with or without GPIIb/IIIa receptor antagonists,
      thrombolysis, or PCI. Although in patients undergoing PCI, LMWH have yet not been
      shown to be superior to UFH they can safely be administered.

PMID- 14965200
TI  - GP IIb/IIIa blockade in elective percutaneous coronary intervention.
AB  - Cumulative scientific evidence gathered over the past ten years has confirmed the
      role of platelet GP IIb/IIIa inhibitors in reducing ischemic complications of
      patients undergoing percutaneous coronary intervention (PCI). Recently, mortality
      data available on more than 20,000 patients enrolled in randomized clinical
      trials suggest that GP IIb/IIIa blockade also improves short and long-term
      survival after PCI. Despite convincing arguments, GP IIb/IIIa inhibitors are
      still inconsistently administered in patients undergoing coronary intervention.
      The following review will discuss the scientific grounds and the principal
      controversies surrounding the use of these compounds in patients undergoing
      elective percutaneous coronary intervention.

PMID- 14965201
TI  - Adjunctive therapy for percutaneous revascularization in acute myocardial
      infarction.
AB  - Primary PCI is an effective reperfusion strategy for acute MI patients, which has
      evolved significantly in the last decade. While many adjunctive therapies have
      contributed to its success, substantial obstacles remain before optimal
      reperfusion can be achieved. Anti-platelet therapy with aspirin, clopidogrel and
      GP IIb/IIIa inhibitors reduces early ischemic complications, improves
      microvascular function and, potentially, affects the inflammatory response to
      ischemic injury. Current anti-thrombin therapy with UFH can be improved with
      LMWH, and, possibly with direct thrombin inhibitors. A number of important
      aspects of this strategy, though, need still to be elucidated. We need to
      optimize microvascular protection before and during PCI in order to capitalize on
      the myocardial sparing effects of reperfusion therapy. This will be probably
      achieved with a combination of pharmacological interventions and mechanical
      emboli protection devices. Improved and more targeted anti-inflammatory therapy
      should decrease the effects of neutrophil-related reperfusion injury, while a
      variety of metabolic interventions might preserve myocardial function during
      ischemia and after reperfusion.

PMID- 14965202
TI  - Gene therapy for cardiovascular diseases.
AB  - Gene therapy is a rapidly evolving field of medicine, which potentially offers
      new treatments for cardiovascular diseases. With the use of gene transfer methods
      it is possible to modify somatic cells in blood vessels and myocardium to
      overexpress or inhibit pathologically important proteins and achieve therapeutic
      effects. Prevention of restenosis after vascular interventions such as
      percutanous coronary angioplasty (PTCA), percutanous peripheral angioplasty (PTA)
      or stent implantation, prevention of venous graft failures and therapeutic
      angiogenesis are the major aims of experimental studies and clinical gene
      therapy. The promise of gene therapy in the treatment of cardiovascular diseases
      remains high. Experimental studies have established the proof of principle that
      gene transfer to cardiovascular system can achieve therapeutic effects. First
      human clinical trials provided initial evidence of the feasibility and safety of
      the novel therapy. There are also first successful reports on the prevention of
      neointimal hyperplasia and promotion of therapeutic angiogenesis in clinical
      trials. However, there are still important questions regarding utility,
      efficiency and safety of gene therapy in the treatment of cardiovascular
      diseases. In this review we discuss the rapid progress in cardiovascular gene
      therapy, the development of delivery systems and vectors, most promising
      therapeutic genes and results of the recent human clinical trials.

PMID- 14965203
TI  - Statin treatment and the natural history of atherosclerotic-related diseases:
      pathogenic mechanisms and the risk-benefit profile.
AB  - Large-scale intervention trials demonstrate that treatment with statins, the most
      effective lipid lowering drug class, significantly reduces the risk of coronary
      heart disease events. Recent evidence suggests that more aggressive LDL
      cholesterol lowering with newly developed statins may provide greater clinical
      benefit, even in individuals with moderately elevated serum cholesterol levels.
      There is increasing evidence that statins exert a myriad of other beneficial
      pleiotropic effects on the vascular wall, thus altering the course of
      atherosclerotic disease. In the long-term treatment, non-life-threatening side
      effects may occur in up to 15% of patients receiving one statin. Significant
      elevations in the activity of serum aminotransferase and creatine kinase alone or
      in combination with muscle pain in statin-treated patients should be taken
      seriously. The combination of the statins with gemfibrozil results in higher
      rates of drug toxicity. Reports show possible adverse effects of statins on
      nervous system function including mood alterations, however, statins have also
      been associated with improvement in central nervous system disorders. Special
      attention must be paid to the tolerability of the statins in children, elderly
      and transplant patients. Future clinical studies and surveillance information
      will warrant long term safety of each member of this class of lipid-lowering
      agents. New classes of patients with diabetes, metabolic syndrome and renal
      diseases may have clinical benefits from statins. New upcoming clinical trials
      will address the fundamental question of whether statin treatment can protect
      from the natural history of atherosclerotic-related diseases. This will require a
      more prolonged follow-up (i.e., 10 to 15 years). Finally, the basic understanding
      of newer pathogenic mechanisms involving the effects of statins on angiogenesis
      and the nitric oxide pathway should be explored in the clinical setting as well
      as the study of pathogenic mechanisms by which statins can affect plaque
      instability.

PMID- 14965204
TI  - Retinoid related molecules an emerging class of apoptotic agents with promising
      therapeutic potential in oncology: pharmacological activity and mechanisms of
      action.
AB  - Retinoic acid and derivatives (retinoids) exert their anti-neoplastic action
      through three different, though partially overlapping mechanisms: growth
      inhibition, cyto-differentiation and apoptosis. Retinoid related molecules (RRMs)
      are a promising class of synthetic retinoic acid derivatives endowed with
      selective apoptotic activity on a large variety of leukemic and solid tumor
      cells. The in vitro apoptotic activity of RRMs translates into in vivo efficacy
      in a number of experimental models of neoplasia. The prototype of this novel
      family of cytotoxic agents is CD437, a conformation restricted retinoid
      originally developed as a selective RARgamma agonist. A number of new RRM
      congeners, including ST1926, MM002, MM11453 and MX-3350-1, have been recently
      reported in the literature. Some of these compounds have a stronger apoptotic
      potential, a lower level of toxicity and a better pharmacokinetic profile than
      CD437. RRMs have a molecular mechanism of action that is entirely different from
      that of many other known chemotherapeutics. These compounds induce apoptosis in
      retinoic acid- and multi-drug-resistant neoplastic cells. The apoptotic process
      triggered by RRMs is independent of p53 activation and proceeds through a novel
      pathway in which the mitochondrion seems to play a pivotal role. RRMs show only
      very limited cross-resistance with other classes of chemotherapeutic agents and
      show synergistic interactions with a number of classical cyto-toxic agents. The
      article presents a critical overview of the current knowledge on the pharmacology
      of RRMs focussing on such issues as the spectrum of cytotoxic activity, the
      molecular mechanisms of action and the pre-clinical basis of clinical
      development.

PMID- 14965205
TI  - Targeted gene silencing by small interfering RNA-based knock-down technology.
AB  - RNA interference (RNAi) has emerged as a powerful tool for the silencing of gene
      expression in animals and plants. RNAi is mediated by approximately 21-nt small
      interfering RNAs (siRNAs), which are originally produced from larger double
      stranded RNAs (dsRNAs) in vivo through the action of Dicer. Recently, many groups
      have reported systems designed to express siRNAs in mammalian cells through
      transfection of either oligonucleotides or plasmids encoding siRNAs. Although the
      use of siRNAs to silence genes in vertebrate cells was only reported three years
      ago, the emerging literature indicates that most vertebrate genes can be studied
      with this technology. This review summarizes some approaches to generate siRNAs,
      the delivery and application of siRNAs to target cells and the utility of siRNAs
      as analytical and potential therapeutic tools.

PMID- 14965206
TI  - Antibodies in diagnostic applications.
AB  - Immunoassays, or assays that are using antibodies as the specific binding
      reagents, have become one of the most common methodologies in diagnostic
      laboratories. In this paper we review different configurations of immunoassays as
      applied to a variety of analytes and sensitivity limits, along with common
      detection techniques and strategies. Progress in developing of ultra high
      affinity antibodies as a direction to improved immunoassays is also reviewed.
      Finally, we specifically concentrate on determination of antibody binding
      constants and performing immunoassays at the single molecule level using
      Fluorescence Correlation Spectroscopy (FCS). This technique has become a powerful
      tool in molecular binding characterizations and assay development, and possibly
      will grow into a quantitative analytical method suitable for diagnostic tests.

PMID- 14965207
TI  - Combinatorial protein biochemistry for therapeutics and proteomics.
AB  - This paper reviews progress towards the customised generation of proteins for
      applications as therapeutics, diagnostics and in proteomics. It particularly
      focuses on combinatorial approaches where proteins with pre-defined biochemical
      and biophysical characteristics are selected from large variant libraries.

PMID- 14965208
TI  - From production of peptides in milligram amounts for research to multi-tons
      quantities for drugs of the future.
AB  - Peptides are key to modern drug discovery. This article reviews the requirements
      for bulk production of peptides and how it affects research and production of
      smaller scales. Peptides, as modern drugs, are currently produced in millions in
      mg-scale for research purpose, in order to better understand the function of
      biological systems. Some newly discovered sequences form the basis of modern
      drugs and are now produced in multi-tons. The most popular example is the T-20
      peptide (Fuzeon), which is the first peptide produced at such scale by a
      combination of solid phase and solution phase methodologies. This particular
      peptide sequence has the ability to dock on the surface of the HIV virus and
      block the virus from entering into a human blood cell, helping patient life
      conditions. A multi-ton scale production was made necessary based on the high
      number of patients, the socio-economical importance of the disease and the strong
      support by governmental institutions such as the FDA. Fuzeon is the first peptide
      based drug that is produced in multi-tons on solid support. This had
      revolutionary effects on the whole peptide synthesis techniques in general
      including the production of the starting materials. It also had a positive impact
      on the cost-effectiveness of peptides for research, as the standard technique for
      producing peptides in research quantities is solid phase chemistry. The decrease
      of the cost of all starting materials will lead to an increase of the number of
      produced peptides, which will certainly bring new interesting and effective
      sequences to be used as novel drugs.

PMID- 14965209
TI  - Detection of tumor markers with ProteinChip technology.
AB  - The early diagnosis of cancer at a curable stage is crucial for the successful
      treatment of this disease. Most of the currently used tumor assays appear too
      late and rely on single biomarkers with high false-negative and/or false-positive
      rates. As an additional burden for the patient, the traditional assays often
      require biopsy material instead of less invasively taken samples like serum. With
      the hope for more reliable DNA- and RNA-based screening tools, the research
      activities of the past 20 years have focused on the genomic characteristics of
      cancer cells. But, up to now, the output from this strategy has been
      disappointingly low and the disillusionment is paired with a return to proteins
      as the real key players in all physiological and pathological processes.
      Meanwhile, comparative protein profiling is generally acknowledged as a promising
      way for the detection of specific and predictive protein patterns reflecting
      certain stages of cancer without dependency on single markers. To meet the new
      technological demands, the ProteinChip Biomarker System was developed for the
      Expression Difference Mapping analysis of several hundreds of samples per day on
      a single, uncomplicated platform; with software support for the construction of
      multi-marker predictive models. The Interaction Discovery Mapping platform is
      introduced as the next methodical step for investigations about protein binding
      partners of possible importance in diagnosis and therapy. This review summarizes
      the current state in cancer diagnosis, provides an introduction into the
      ProteinChip technology, and gives an update on publications and research
      collaborations in SELDI-based tumor marker discovery.

PMID- 14965210
TI  - Tracking cell signaling protein expression and phosphorylation by innovative
      proteomic solutions.
AB  - The most challenging and fruitful biomedical research endeavor of this decade
      will be the mapping of cell signaling systems and establishing their linkages to
      normal and disease-related processes. Amongst other things, the Human Genome
      Sequencing Project has greatly facilitated MALDI-TOF mass spectrometry
      identification of proteins that have been resolved by standard 2D gel
      electrophoresis. However, the low abundance of protein kinases and other signal
      transduction proteins has rendered their analyses particularly problematic
      without some means of purification and enrichment from cell and tissue lysates.
      Antibodies have been the most specific affinity probes for tracking target
      proteins, but their variable quality and high cost preclude their deployment in
      most discovery-based proteomics studies. Current multi-immunoblotting techniques
      can permit the probing of a single mini-SDS-PAGE gel with 50 or more antibodies
      at a time to monitor large changes in the expression and phosphorylation states
      of signaling proteins. The development of new affinity probes to replace
      antibodies is necessary to drive large scale proteomics studies. Such affinity
      probes could include short peptide antibody mimetics (PAM's) and oligonucleotide
      aptamers that when spotted in 2D array formats (e.g. membrane macroarrays, glass
      microarrays) or presented on specific beads (e.g. Luminex beads) can capture
      target proteins for their specific enrichment. The bound target proteins can then
      be detected using reporter antibodies or other specific probes for their
      quantitation by high throughput systems. These new proteomics methodologies will
      accelerate assessment of specific protein expression, post-translational
      modification, protein-protein interactions and protein-drug interactions to
      provide a more holistic view of cellular operations and how they might be
      manipulated under pathological circumstances.

PMID- 14965211
TI  - Bioinformatics in proteomics.
AB  - Proteomics technologies are under continuous improvements and new technologies
      are introduced. Nowadays high throughput acquisition of proteome data is
      possible. The young and rapidly emerging field of bioinformatics in proteomics is
      introducing new algorithms to handle large and heterogeneous data sets and to
      improve the knowledge discovery process. For example new algorithms for image
      analysis of two dimensional gels have been developed within the last five years.
      Within mass spectrometry data analysis algorithms for peptide mass fingerprinting
      (PMF) and peptide fragmentation fingerprinting (PFF) have been developed. Local
      proteomics bioinformatics platforms emerge as data management systems and
      knowledge bases in Proteomics. We review recent developments in bioinformatics
      for proteomics with emphasis on expression proteomics.

PMID- 14965212
TI  - Clinical applicability of mass spectrometry for inhaled carbon compounds and the
      characterization of trace element patterns in body fluids.
AB  - So far, chemists, molecular biologists and biochemists have reaped the greatest
      benefits from mass spectrometry (Aebersold et al., 2003). This type of analysis
      could, however, be useful in many fields. Mass spectrometry is on its way to the
      doctor's office (Pusch et al., 2003; Foldes-Papp et al., 2002; Henry 1999). The
      article is focused on laser-activated microprobe mass analysis (LAMMA) and
      inductively coupled argon plasma mass spectrometry (ICP-MS). Potential
      applications of the two types of mass spectrometry are demonstrated in clinical
      medicine. It is the first comprehensive review on qualitative characterization of
      carbonaceous compounds in lung tissue samples in situ and quantitative trace
      element determination in body fluids.

PMID- 14965213
TI  - Moderate hyperhomocysteinemia and immune activation.
AB  - Moderate hyperhomocysteinemia is associated with an increased risk of
      atherosclerosis, thrombosis and neurodegenerative diseases. Homocysteine
      accumulation in the blood can be due to many underlying causes, which may
      interact with each other, e.g. genetic disposition and B-vitamin status. The role
      of the sulfur-containing amino acid homocysteine in the pathogenesis of diseases
      remains unclear, even if many studies suggest a causal relationship between
      homocysteine-mediated processes like oxidative stress, NO-inactivation and
      endothelial deficiency and atherogenesis. Proposed mechanisms of action of
      homocysteine are discussed, and the question is addressed, whether effects that
      are attributed to homocysteine, are not rather the consequence of folate and
      vitamin B12-deficiency. Deficiency of these B-vitamins in parallel with moderate
      hyperhomocysteinemia is often found in patients with enhanced activation of the
      cellular immune system, like Alzheimer's disease, rheumatoid arthritis and also
      vascular diseases. In patients with these diseases an association between
      homocysteine metabolism, oxidative stress and immune activation exists. On the
      one hand proliferation of immunocompetent cells having an enhanced demand for B
      vitamins leads to the accumulation of homocysteine. On the other hand macrophages
      stimulated by TH1-type cytokine interferon-gamma form reactive oxygen species
      (ROS), which oxidize antioxidants, lipoproteins and oxidation-sensitive B
      vitamins. Thereby Th1-type immune response could contribute importantly to the
      development of hyperhomocysteinemia, and may also be a major determinant of
      disease progression.

PMID- 14965214
TI  - Optimal enzymes for single-molecule sequencing.
AB  - Much research effort has been made to realize a single-molecule sequencing.
      Central to this project are two enzymatic tasks that challenged several
      biochemists during the last years. They searched for polymerases for copying a
      DNA target into completely fluorophore-labeled DNA as well as for handling this
      new DNA derivative. Furthermore, they studied exonucleases for the sequential
      hydrolysis of completely dye-labeled DNA and explored optimal conditions for
      future application on the single-molecule level. In this article, the recent
      advances will be summarized from the biochemist's point of view.

PMID- 14965220
TI  - Intravenous and regional paclitaxel formulations.
AB  - Paclitaxel has been proven to be effective against different types of cancer. A
      delivery system loaded with paclitaxel at tumor site should provide a high local
      concentration of the drug detrimental to malignant cells, which prevents the re
      growth and metastasis of tumor. In this review, paclitaxel formulations for
      systemic and for intratumoral administration are discussed.

PMID- 14965221
TI  - Glucocorticoids selectively inhibit paclitaxel-induced apoptosis: mechanisms and
      its clinical impact.
AB  - Paclitaxel (Taxol), a naturally occurring antimitotic agent, has shown
      significant cell-killing activity against tumor cells through induction of
      apoptosis. The mechanism by which paclitaxel induces cell death is not entirely
      clear. Recent studies in our laboratory discovered that glucocorticoids
      selectively inhibited paclitaxel-induced apoptosis without affecting the ability
      of paclitaxel to induce microtubule bundling and mitotic arrest. This finding
      implies that apoptotic cell death induced by paclitaxel may occur via a pathway
      independent of mitotic arrest. Through analyses of a number of apoptosis
      associated genes or regulatory proteins, we found that glucocorticoids and
      paclitaxel possess opposite regulatory role in the NF-kappa B/Ikappa Balpha
      signaling pathway. Further studies indicate that paclitaxel activates Ikappa B
      Kinase (IKK), which in turn causes degradation of Ikappa Balpha and activation of
      NF-kappa B, whereas glucocorticoids antagonize paclitaxel-mediated NF-kappa B
      activation through induction of Ikappa Balpha synthesis. These results suggest
      that the NF-kappa B/Ikappa Balpha signaling pathway might play a critical role in
      the mediation or regulation of paclitaxel-induced cell death. On the other hand,
      since glucocorticoids (such as dexamethasone) are routinely used in the clinical
      application of paclitaxel to prevent hypersensitivity reactions and other adverse
      effects, the inhibitory action of glucocorticoids on paclitaxel-induced apoptosis
      also raises a clinically relevant question as to whether the pretreatment with
      glucocorticoids might interfere with the therapeutic efficacy of paclitaxel.

PMID- 14965222
TI  - Nanoparticles of biodegradable polymers for clinical administration of
      paclitaxel.
AB  - Paclitaxel is one of the best antineoplastic drugs found from nature in the past
      decades, which has been found effective against a wide spectrum of cancers
      including ovarian cancer, breast cancer, small and non small cell lung cancer,
      colon cancer, head and neck cancer, multiple myeloma, melanoma, and Kaposi's
      sarcoma. Like many other anticancer drugs, it has difficulties in clinical
      administration due to its poor solubility in water and most pharmaceutical
      reagents. In its current clinical application, an adjuvant called Cremophor EL
      has to be employed, which has been found to be responsible for many serious side
      effects. Nanoparticles of biodegradable polymers can provide an ideal solution to
      such an adjuvant problem and realize a controlled and targeted delivery of the
      drug with better efficacy and less side effects. With further development, such
      as particle size optimization and surface coating, nanoparticle formulation of
      paclitaxel can promote a new concept of chemotherapy to realize its full efficacy
      and to improve quality of life of the patients, which includes personalized
      chemotherapy, local chemotherapy, sustained chemotherapy, oral chemotherapy,
      chemotherapy across the blood-brain barrier, chemotherapy across the
      microcirculation barrier, etc. The present research proposes a novel formulation
      for fabrication of nanoparticles of poly(lactic-co-glycolic acid) (PLGA) by a
      modified solvent extraction/evaporation technique, in which natural emulsifiers,
      such as phospholipids, cholesterol and vitamin E TPGS are creatively applied to
      achieve high drug encapsulation efficiency, desired drug released kinetics, high
      cell uptake and high cytotoxicity. The nanoparticles composed of various recipes
      and manufactured under various conditions were characterized by laser light
      scattering (LLS) for size and size distribution, scanning electron microscopy
      (SEM) and atomic force microscopy (AFM) for morphological properties, X-ray
      photoelectron spectroscopy (XPS) and Fourier Transformation Infrared Spectroscopy
      (FTIR) for surface chemistry, zeta-potential for surface charge, and differential
      scanning calorimetry (DSC) for the thermogram properties. The drug encapsulation
      efficiency and the drug release kinetics under in vitro conditions were measured
      by high performance liquid chromatography (HPLC). It was found that these natural
      emulsifiers have great advantages for nanoparticle formulation of paclitaxel over
      the traditional macromolecular emulsifiers, such as polyvinyl alcohol (PVA).
      Nanoparticles of desired small size and narrow size distribution can be obtained.
      The drug encapsulation efficiency can be achieved as high as 100 %. The released
      kinetics can be made under control. The HT-29 cancer cell line experiment showed
      that after 24 hours of incubation, the cell mortality caused by the drug
      administered by such nanoparticle formulation could be more than 13 times higher
      than that caused by the free drug under similar conditions.

PMID- 14965223
TI  - Chronic administration of single weekly paclitaxel in heavily pretreated ovarian
      cancer patients.
AB  - Ovarian cancer patients with paclitaxel-resistance have been reported to respond
      to a weekly schedule of the same drug. In this report, two cases with long
      progression free interval by weekly paclitaxel (T) are presented. Case 1. A 41
      year-old Japanese woman, gravida 2, para 0, was referred to our hospital in
      September 16, 1998, because of abdominal mass accompanying large amount of
      ascites with elevated CA125 (8400 U/ml) and CA19-9 (770 U/ml). Exploratory
      laparotomy (tumor biopsy plus partial omentectomy) was performed September 21,
      1998. After the surgery, the tumor was diagnosed as serous cystadenocarcinoma of
      the ovary (stage IV) and 6 cycles of treatment consisting of cyclophosphamide,
      adriamycin and cisplatin (CAP) were performed. The CA 125 level (8400 U/ml)
      rapidly declined to 150 U/ml by this CAP therapy. After second cytoreductive
      surgery (SRS) (total hysterectomy and bilateral salpingo-oophorectomy), residual
      tumor was less than 2 cm. Although 7 cycles of CAP was added, ascites and
      elevation of CA 125 (5100 U/ml) were observed. Therefore, treatment with single
      weekly T was performed and CA 125 levels remained between 70-90 U/ml during 13
      cycles of this therapy (progression free interval; more than 1 year). Thereafter,
      she is alive with disease and followed-up. Case 2. A 48-year-old Japanese woman,
      gravida 3, para 2, was referred to our hospital in July 22, 1998, because of
      abdominal swelling and pain. Computing tomography (CT) and magnetic resonance
      imaging (MRI) revealed large amount of ascite and pelvic mass (9 x 7 x 7 cm), and
      low density area (3 x 3 cm) suggesting metastasis in right lobe of liver. Serum
      CA 125 level elevated to 5100 U/ml. Bilateral salpingo-oophorectomy and
      infracolic omentectomy were performed on August 5, 1998. The tumor was diagnosed
      as endometrioid adenocarcinoma of the ovary, stage IV and chemotherapy with CAP
      was initiated on September 5, 1998. After 6 cycles of CAP, SRS was performed.
      After SRS, 3 cycles of CAP were added and changed to weekly T because of damage
      of renal function. The CA 125 level returned within normal range during weekly T.
      Total 13 cycles of weekly T were performed and progression free interval was
      about 18 months. Thereafter, she received treatments with gamma knife and CAP for
      brain metastasis. She is alive without disease and followed-up. Side effects by
      weekly T were mild and tolerable despite of long term treatment. In addition,
      weekly T can be safely used in outpatient setting and even in patients with poor
      performance status (PS), and warrant long time to progression.

PMID- 14965224
TI  - Tumor specific novel taxoid-monoclonal antibody conjugates.
AB  - The basic principle of the targeted delivery approach is that the conjugation of
      a drug to a tumor-specific molecule renders the drug inactive until it reaches
      the target site. Monoclonal antibodies (mAbs), which have shown high binding
      specificity for tumor-specific antigens, could be used as targeting agents.
      Paclitaxel has brought significant impact on the current cancer chemotherapy, but
      seriously suffers from the lack of tumor specificity. A series of paclitaxel
      monoclonal antibody conjugates via C-2' ester linkage were reported. Taking into
      account the fact that the cytotoxicity of paclitaxel is not good enough and thus
      not applicable to this target delivery prodrug approach, new taxoids bearing
      methyldisulfanyl(alkanoyl) groups were designed, synthesized, and their
      activities evaluated. A highly cytotoxic C-10 methyldisulfanyl-propanoyl taxoid,
      was conjugated to monoclonal antibodies recognizing the epidermal growth factor
      receptor (EGFR). These conjugates were shown to possess remarkable target
      specific antitumor activity in vivo against EGFR-expressing A431 tumor xenografts
      in SCID mice, resulting in complete inhibition of tumor growth in all the treated
      mice without any noticeable toxicity to the animals.

PMID- 14965225
TI  - Paclitaxel antibody conjugates and trehalose for preserving the immunological
      activity after freeze-drying.
AB  - Antibodies and anticancer drug-antibody conjugates used in experimental cancer
      research or clinically must be freeze-dried for preserving the activity and
      storage at room temperature. This often results in some denaturation and loss of
      activity. We describe a recovery of the cytotoxic activity of a paclitaxel-mAb
      immunoconjugate after freeze-drying. The paclitaxel-antibody conjugate specific
      for ovarian cancer was tested both for its cytotoxicity in vitro and
      immunological activity after freeze drying in the presence of various
      preservatives. Results show that the inclusion of trehalose as a stabilizer at
      concentrations varying from the 0.25 and 0.40 M protected the antibody and saved
      the pharmacological activity. When PEG alone or with trehalose was used, the
      immunological and cytotoxic activities recovery were lower. Albumin was not
      protective. This study shows that the addition of trehalose for freeze drying
      labile drug is a promising method for storage of large quantities of the
      immunoconjugates for experimental and therapeutic use.

PMID- 14965226
TI  - Cytokines in the thymus: production and biological effects.
AB  - All types of thymic cells are able to produce cytokines either spontaneously or
      after stimulation. The main producers of cytokines in the thymus are thymic
      epithelial cells (TEC) and thymocytes. Thymic cytokines act at short distance and
      their effects are limited by the internal space of the organ. The spectrum of
      biological effects of thymic cytokines is determined by the expression of
      cytokine receptors on the thymic cell surface. Some cytokines produced by the
      thymic cells of one type are supplied to cells of other types; other cytokines
      act as autocrine factors. Examples of paracrine thymic cytokines are IL-7
      (produced by TEC or stromal fibroblasts induces CD4(-)CD8(-) thymocyte growth and
      differentiation) and INFgamma (produced by thymocytes, induces TEC activation).
      An example of an autocrine factor is IL-2, for which the producers and targets
      are thymocytes. The ability of thymocytes to produce cytokines and express
      cytokine receptors is gradually reduced as they mature from the stage of
      CD44(+)CD3(-)CD4(-)CD8(-) precursor cells to the stage of CD3(lo)CD4(+)CD8(+)
      cortical thymocytes; in the latter stage both these capacities become completely
      blocked. This change reflects the decrease of cytokine dependence of the
      respective processes. After the completion of the selection process, the capacity
      of thymocytes to produce cytokines and respond to their action is restored. Some
      differences in the function of the cytokine system in thymus and peripheral
      compartments of the immune system can be noted. 1. Unlike the periphery, where
      cytokine production and receptor expression are inducible, the synthesis of
      cytokines and expression of their receptors in the thymus has mainly a
      "spontaneous" character (or it is induced by cell-cell interactions). 2.
      Cytokines tightly interact, forming a cytokine network both at the periphery and
      in the thymus, but the structure of the peripheral and intrathymic cytokine
      network is different. The latter can be termed as a "minor cytokine network".
      Some peptide hormone-like factors play a significant role in the intrathymic
      cytokine network. 3. The principal role of thymic cytokines is to provide
      constitutive processes (migration and development of thymocytes, regulation of
      cell number in the cell populations, etc.), but not inducible ones (inflammation,
      immune response, etc.) as in the periphery. 4. The functions of some cytokines in
      the thymus can be significantly different from those in the periphery of the
      immune system. For example, proinflammatory cytokines act in the thymus as
      factors or cofactors of thymocyte or TEC activation, proliferation or
      differentiation. The key cytokines of Th1 and Th2 cells - IFNgamma and IL-4 - do
      not participate in the immune response but mediate the dialogue between thymocyte
      and TEC and play a role in autoregulating the thymocyte population. The functions
      of many cytokines in the thymus are not established up to now. Detailed analysis
      of the "minor cytokine network" and intrathymic cytokine effects will reveal some
      unknown events of thymus physiology.

PMID- 14965227
TI  - Sorbitol dehydrogenase: structure, function and ligand design.
AB  - Sorbitol dehydrogenase (SDH), a member of the medium-chain
      dehydrogenase/reductase protein family and the second enzyme of the polyol
      pathway of glucose metabolism, converts sorbitol to fructose strictly using
      NAD(+) as coenzyme. SDH is expressed almost ubiquitously in all mammalian
      tissues. The enzyme has attracted considerable interest due to its implication in
      the development of diabetic complications and thus its tertiary structure may
      facilitate the development of drugs for the treatment of diabetes sufferers.
      Modelling studies suggest that SDH is structurally homologous to mammalian
      alcohol dehydrogenase with respect to conserved zinc binding motif and a
      hydrophobic substrate-binding pocket. Recently, the three-dimensional (3-D)
      structure of a mammalian SDH was solved, and it was found that while the overall
      3-D structures of SDH and alcohol dehydrogenase are similar, the zinc
      coordination in the active sites of the two enzymes is different. The available
      structural and biochemical information of SDH are currently being utilized in a
      structure-based approach to develop drugs for the treatment or prevention of the
      complications of diabetes. This review provides an overview of the recent
      advances in the structure, function and drug development fields of sorbitol
      dehydrogenase.

PMID- 14965228
TI  - Expression and function of the leukocyte integrins in organ transplant rejection.
AB  - Many immune responses are dependent on the four members of the leukocyte integrin
      family of surface receptors. Organ transplantation triggers a range of immune
      responses aimed at rejecting the donor tissue. Engagement of cells of the immune
      system including T cells, B cells, and antigen presenting cells with each other
      or with the donor organ is an essential element of the rejection cascade, and
      this engagement is mediated by adhesions through the leukocyte integrins and
      their ligands. This review will first focus on the molecular mechanisms that
      regulate rapid activation of the leukocyte integrins by inside-out signaling that
      results in changes in receptor clustering on the leukocyte membrane and ligand
      affinity. Longer lasting changes in receptor expression through transcriptional
      mechanisms will also be discussed. The role of these receptors in organ
      transplant rejection, graft-versus-host disease, and ischemic reperfusion injury
      will also be reviewed. The potential of anti-adhesion therapy to prolong organ
      transplant survival will be discussed in both animal and patient studies.

PMID- 14965229
TI  - Promiscuous beta-strand interactions and the conformational diseases.
AB  - Conformational change plays an important role in the life of all proteins,
      starting from when they fold, through their function and often their fate. For an
      increasing number of proteins inappropriate conformational change leads to a
      chain of events, which culminate in the deposition of proteinacious aggregates
      and disease. In this review we consider the current literature on a number of
      proteins which form part of the Conformational Disease family. We describe here
      two types of aggregate that can be formed, Type I aggregates are typified by the
      Serpin superfamily and consist of non-fibrillar polymeric species. Type II
      aggregates are of the classical fibrillar form formed by a diverse range of
      proteins. Through biochemical and biophysical analysis of the aggregation
      reaction of members of these two classes we show that they form these aggregates
      through highly similar pathways. Essentially, the whole process can be summed up
      in two key stages. Firstly, the existence of conditions which increase the
      conformational flexibility of the protein, enabling it to adopt a partially
      folded state. Secondly, the propensity of this intermediate conformer to form
      intermolecular linkages leads to multimeric forms, a step often mediated via
      hydrophobic or beta -strand interactions. Our understanding of these structural
      changes has facilitated the rationale design of specific aggregation inhibitors.
      We will discuss the successes and pitfalls of such approaches to demonstrate how
      similar approaches may be applied to any misfolding protein.

PMID- 14965230
TI  - Regulation of synthesis and trafficking of canalicular transporters and its
      alteration in acquired hepatocellular cholestasis. Experimental therapeutic
      strategies for its prevention.
AB  - Bile formation is an osmotic process driven by the vectorial transport of
      actively transferred biliary components across the basolateral (sinusoidal) and
      apical (canalicular) hepatocyte membranes, the latter being the rate-limiting
      step of the overall blood-to-bile transfer. The ATP-binding cassette (ABC)
      superfamily of membrane transporters comprises novel ATP-dependent carriers that
      mediate canalicular transfer of several endogenous and exogenous substrates, and
      therefore play a key role in bile formation. Gene expression, as well as the
      balance between vesicular targeting and internalization of these transporters
      to/from the canalicular membrane are highly regulated processes. This balance is
      affected in several models of hepatocellular cholestasis, and these alterations
      may either initiate or perpetuate the cholestatic manifestations. This review
      describes the regulation of the normal activity of hepatocellular ABC
      transporters, focusing on the involvement of transcription factors and signaling
      pathways in the regulation of carrier synthesis, dynamic localization and
      phosphorylation status. Its alteration in different experimental models of
      cholestasis, such as those induced by estrogens, lipopolysaccharide (endotoxin),
      monohydroxylated bile salts and oxidative stress, is also reviewed. Finally,
      several experimental therapeutic approaches based upon the administration of
      compounds known/thought to induce carrier synthesis (e.g., protein synthesis
      inducers), to counteract etiological factors responsible for the cholestatic
      disease (e.g., corticoids in lipopolysaccharide-induced cholestasis) or to
      stimulate exocytic insertion of canalicular transporters (e.g., cAMP, silymarin
      or tauroursodeoxycholate) are described with respect to their ability to prevent
      cholestatic alterations; the role of signaling molecules as putative downstream
      mediators of their effects are also discussed.

PMID- 14965231
TI  - Schizophrenia: from dopamine to glutamate and back.
AB  - The first part of the present review describes the exciting journey of dopamine
      stabilizers, starting in the early eighties with the development of the partial
      dopamine agonist (-)-3-PPP of phenylpiperidine structure, via various compounds
      with aminotetraline structure with preferential autoreceptor antagonist
      properties, and then back again to phenylpiperidine compounds carrying
      substituents on the aromatic ring that transformed them from partial dopamine
      agonists to partial dopamine receptor antagonists, such as OSU6162. OSU6162 was
      brought to the clinic and has in preliminary trials showed antidyskinetic and
      antipsychotic efficacy. The second part of this review describes results from a
      hypoglutamatergia mouse model for cognitive symptoms of schizophrenia, where we
      have tested traditional neuroleptics, new generation antipsychotics with marked 5
      HT2 vs dopamine D2 receptor blockade as well as a dopamine stabilizer belonging
      to the partial dopamine receptor antagonist category.

PMID- 14965232
TI  - Atypical antipsychotics: pharmacokinetics, therapeutic drug monitoring and
      pharmacological interactions.
AB  - The development of new "atypical" antipsychotic agents, which are safer than
      classical neuroleptics and also active against the negative symptoms and
      neurocognitive deficits caused by the illness, has produced a significant
      advancement in the treatment of schizophrenia. The atypical (or "second
      generation") antipsychotics have several therapeutical properties in common,
      however they can significantly differ with regard to clinical potency and side
      effects. The main features regarding pharmacodynamics, pharmacokinetics and
      pharmacological interactions of the most important atypical antipsychotics,
      namely clozapine, olanzapine, quetiapine and risperidone, are treated herein.
      Several analytical methods available for the therapeutic drug monitoring of these
      drugs are also presented, as well as the novel formulations, which can notably
      improve the therapy of schizophrenia. Other very recent atypical agents, such as
      ziprasidone, aripiprazole, iloperidone, sertindole and zotepine will also be
      briefly described.

PMID- 14965233
TI  - Pharmacogenomic-guided rational therapeutic drug monitoring: conceptual framework
      and application platforms for atypical antipsychotics.
AB  - Atypical antipsychotic agents such as aripiprazole, clozapine, olanzapine,
      quetiapine and ziprasidone offer many advantages over conventional neuroleptics.
      These agents reduce negative symptoms of schizophrenia, are effective in
      treatment refractory cases, and have a markedly lower incidence of extrapyramidal
      symptoms and tardive dyskinesia. However, there is considerable patient-to
      patient variability in therapeutic dose requirements of atypical antipsychotics
      and the propensity for side effects. Hence, the initial excitement since the
      introduction of atypical antipsychotics in late 1980s is now shifting towards a
      focus on individualization of pharmacotherapy and elucidation of the mechanistic
      basis of interindividual variability in drug response with use of pharmacokinetic
      and pharmacodynamic biomarkers. Pharmacogenomics, introduced in late 1990s, is
      the study of variability in drug response using information from the entire
      genome of a given individual patient. Both pharmacogenomics and conventional
      therapeutic drug monitoring (TDM) share the similar goal of improving
      pharmacotherapy through better explanation of individual variability in drug
      response. Hence, pharmacogenomic biomarkers offer a unique opportunity to
      complement and expand the scope of traditional TDM in clinical
      psychopharmacology. Importantly, pharmacogenomics enables the investigation of
      factors distal to drug exposure in the plasma compartment (e.g. drug targets at
      the biophase), thereby providing a more complete portrayal of sources of
      variability in psychotropic drug response. We discuss (1). the definitions for
      biomarkers and surrogate endpoints in the context of pharmacogenomics, (2).
      genetic variations in isozyme-specific atypical antipsychotic metabolism in vivo,
      (3). selected examples of pharmacogenomic variability in pertinent drug targets
      and, (4). the anticipated roadmap from implementation of pharmacogenomics to
      changes in healthcare and therapeutic policy. In addition, a conceptual framework
      that outlines the theoretical advantages of pharmacogenomics-guided TDM is
      presented using recent clinical applications as precedence.

PMID- 14965234
TI  - A critical review of atypical antipsychotic utilization: comparing monotherapy
      with polypharmacy and augmentation.
AB  - The atypical antipsychotics risperidone, olanzapine, quetiapine, ziprasidone, and
      aripiprazole have become first-line treatment for schizophrenia because they
      reduce the positive symptoms of psychosis but do not have a high incidence of
      extrapyramidal symptoms. However, these agents, like other antipsychotics, may
      take as long as 16 or more weeks to produce a response, and even with prolonged
      treatment are unlikely to evoke responses greater than 50% improvement in
      symptoms. This has led to the experimental use of high atypical antipsychotic
      doses, antipsychotic polypharmacy, and augmentation with other psychotropic
      drugs, all of which occur commonly in clinical practice. This article reviews the
      current evidence for these increasingly common means of treating schizophrenia
      and psychosis, with particular emphasis on polypharmacy and augmentation. To
      date, there are only two controlled studies of antipsychotic polypharmacy
      involving an atypical antipsychotic; the rest of the data are uncontrolled trials
      and case reports that describe a mixture of positive and negative findings. One
      multicenter, double-blind trial shows a faster onset of action when divalproex is
      added to risperidone or olanzapine than with antipsychotic monotherapy. A small
      double-blind study demonstrates efficacy when lamotrigine is added to clozapine.
      The rest of the data on augmentation with anticonvulsants are uncontrolled, and
      most report adverse effects. With the exception of divalproex, there are
      currently no compelling data to justify the use of antipsychotic polypharmacy or
      augmentation. Existing evidence suggests that the best treatments for
      schizophrenia and psychosis may be long-term trials of a sequence of atypical
      antipsychotic monotherapies at therapeutic doses.

PMID- 14965235
TI  - Naturalistic studies of second generation antipsychotics in the treatment of
      schizophrenia.
AB  - Undoubtedly, the pharmacological treatment of schizophrenia has changed
      dramatically over the last 10 years. Large, double-blind, placebo-controlled
      trials have ushered the availability of each new antipsychotic. However, there
      has been an information lag because of the relative paucity of long term,
      comparative studies among second-generation antipsychotics. While we await such
      evidence, naturalistic studies have helped to provide useful information on the
      pattern of use, patient response, and tolerability of these new agents in
      clinical practice. This review provides an account of representative studies for
      each second generation antipsychotic, which illustrate the contributions of
      naturalistic studies to our understanding of the evolving pharmacotherapy of
      schizophrenia.

PMID- 14965236
TI  - New antipsychotics and schizophrenia: a review on efficacy and side effects.
AB  - The first compounds showing efficacy in the treatment of schizophrenia and other
      psychotic disorders was chlorpromazine, an anti-histaminic compound casually
      observed to possess antipsychotic effects. The discovery of the real mechanism of
      action of antipsychotic substances dates back to the 1960s, when researchers
      found that these compounds act as dopamine receptor antagonists. Unfortunately,
      this type of drugs cannot block the D2 receptors only in the mesolimbic
      dopaminergic pathway (which mediates their therapeutic effects), because of their
      non-selective D2 receptor blockage in both the mesolimbic and striatal regions,
      and the consequent appearance of side effects related to striatal interaction in
      the same dosage range as is needed for the therapeutical effects. Clozapine,
      discovered in the early 1970s, seemed to represent the solution to contrast these
      side effects, as it possesses antipsychotic activity without inducing
      extrapyramidal disorders in humans or catalepsy in rats; for this reason, it was
      defined as an "atypical" antipsychotic drug. Later, other beneficial properties,
      such as improvement of negative symptoms and of cognitive dysfunction and
      efficacy in neuroleptic-resistant schizophrenia, were included in the definition
      of "atypical". In recent years, the appearance of new atypical antipsychotics
      (risperidone, olanzapine, quetiapine, ziprasidone) has opened new ways to
      therapy. The aim of this paper is to review literature about newer
      antipsychotics, focusing on their advantages in terms of efficacy and side effect
      profiles when compared to classical and older atypical antipsychotics, and to
      evaluate the efficacy of the different new antipsychotics when compared to one
      another.

PMID- 14965237
TI  - Mode of action of endotoxin: role of free radicals and antioxidants.
AB  - The pathogenetic sequence of reactions mediated by endotoxin (LPS) leading to the
      production of sepsis involves the oxygen radicals or reactive oxygen species,
      which has been evaluated in the present review. Among reactive oxygen species
      hydroxyl radical either singly or in combination with peroxynitrite, produces
      tissue damage often observed during septic injury. Inactivation of these damaging
      radicals by antioxidants or nitric oxide inhibitor(s) may be helpful for
      protecting sepsis mediated derangements but the application of these agents as
      drugs in humans has not been fully successful. Transcription factor NF-kappa B is
      reported to be the oxygen sensor in LPS induced endotoxemia. Polyphenols,
      especially the catechin group of compounds, are important therapeutic agents,
      which may be used for the treatment of endotoxin mediated sepsis.

PMID- 14965238
TI  - Oxidative stress-induced ischemic heart disease: protection by antioxidants.
AB  - Heart disease is one of the major health problems of advanced as well as
      developing countries of the world. Extensive research through the last decade has
      shown beyond doubt that free radicals, particularly, reactive oxygen species play
      a cardinal role in the pathogenesis of oxidative myocardial damage with
      consequential cardiac malfunction. This review presents a comprehensive account
      of the present day knowledge regarding the oxygen free radicals involved in the
      genesis of ischemic heart disease, the mechanism(s) of oxidative myocardial
      damage and the endogenous as well as exogenous antioxidant defense systems.
      Furthermore, the role of ischemic pre-conditioning, some antioxidants and the
      ability of some cardioprotective drugs in providing protection against the
      ischemic myocardial damage are also discussed. The text of the article comes to
      an end with a commentary on the future research perspective in the concerned
      area, which throws a light on the development of combinatorial therapeutics in
      the treatment of ischemic myocardial disease.

PMID- 14965239
TI  - The NMDA receptor NR2B subunit: a valid therapeutic target for multiple CNS
      pathologies.
AB  - The NMDAR2B subunit is the focus of increasing interest as a therapeutic target
      in a wide range of CNS pathologies, including acute and chronic pain, stroke and
      head trauma, drug-induced dyskinesias, and dementias. Due to significant
      pharmaceutical endeavor, an impressive collection of chemical leads has been
      developed which target the NR2B subunit, some of which appear to discriminate
      between closely related subtypes. We now have the benefit of a structural
      template for the ifenprodil binding site which should further improve future
      structure activity relationships. A growing appreciation of the likely
      extrasynaptic localisation of the NR2B receptor subtype and importance of NR2B
      protein modification, notably tyrosine phosphorylation, may explain its
      therapeutic importance. The apparent superior preclinical and clinical data for
      the second and third generation NR2B compounds is likely to reflect subtype
      selectivity, a unique mode of action and cellular location of the NR2B receptors
      in the CNS.

PMID- 14965240
TI  - 5-HT1 receptors.
AB  - Among the seven classes of serotonin (5-hydroxytryptamine, 5-HT) receptors which
      have been identified to date, the 5-HT(1) class is comprised of five receptor
      types, with the 5-HT(1A), 5-HT(1B) and 5-HT(1D) characterized by a high affinity
      for 5-carboxamido-tryptamine, the 5-HT(1E) and 5-HT(1F) characterized by a low
      affinity for this synthetic agonist, and all five having a nanomolar affinity for
      the endogenous indolamine ligand. The genes encoding 5-HT(1) receptors have been
      cloned in both human and rodents, allowing the demonstration that they all belong
      to the G-protein-coupled receptor super-family with the characteristic 7
      hydrophobic (transmembrane) domain-containing amino acid sequence. All the 5
      HT(1) receptor types actually interact with G alpha i/G alpha o proteins to
      inhibit adenylyl cyclase and modulate ionic effectors, i.e. potassium and/or
      calcium channels. Probes derived from the knowledge of amino acid sequence of the
      receptor proteins and of nucleotide sequence of their encoding mRNAs allowed the
      mapping of all the 5-HT(1) receptor types in the central nervous system and other
      tissues. For the last twenty years, both pharmacological investigations with
      selective agonists and antagonists and phenotypical characterization of knock-out
      mice have been especially informative regarding the physiological implications of
      5-HT(1) receptor types. This research ends notably with the development of
      triptans, whose agonist activity at 5-HT(1B), 5-HT(1D) and 5-HT(1F) receptors
      underlies their remarkable efficacy as antimigraine drugs. Clear-cut evidence of
      the implication of 5-HT(1) receptors in anxiety- and depression-like behaviours
      and cognitive performances in rodents should hopefully promote research toward
      development of novel drugs with therapeutic potential in psychopathological and
      dementia-related diseases.

PMID- 14965241
TI  - 5-HT2 receptors.
AB  - 5-HT(2) receptors are G-protein coupled receptors that currently comprise three
      subtypes: 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. The subtypes are related in
      their molecular structure, amino acid sequence and signaling properties. 5-HT(2A)
      and 5-HT(2C) receptors have a widespread distribution and function in the central
      nervous system. 5-HT(2A)and 5-HT(2C) receptor antagonism is a property of certain
      antipsychotic and antidepressant drugs. 5-HT(2B) receptors have a restricted
      expression in the central nervous system. They have an important role in
      embryogenesis and in the periphery. In this article, selected aspects of 5-HT(2)
      receptor research are reviewed for each subtype under three main headings : (i)
      genes, protein structure and receptor signaling; (ii) receptor localization with
      emphasis on the CNS and (iii) compounds. The general discussion reflects on the
      reasons for the limited success in the clinic of 5-HT(2) receptor subtype
      selective drugs.

PMID- 14965242
TI  - 5-HT3 receptors.
AB  - 5-HT(3)-receptor antagonists are highly selective competitive inhibitors of the 5
      HT(3)-receptor with negligible affinity for other receptors. They are potent,
      rapidly absorbed and easily penetrate the blood-brain barrier; metabolized by the
      cytochrome P450-system with half-life varying from 3-10 hours. The compounds
      investigated so far do not modify normal behaviour in animals or man and are well
      tolerated over wide dose ranges, the most common side effects being headache or
      constipation. Clinical efficacy was first established in chemotherapy-induced
      emesis (and then in radiotherapy-induced and post-operative emesis), where 5
      HT(3)-receptor antagonists set a new standard of antiemetic efficacy and
      tolerability. The 5-HT(3) receptor antagonists, via a central and / or peripheral
      action, have been shown to reduce secretion and motility in the gut and possess
      clinical utility in irritable bowel syndrome, and possibly other visceral pain
      disorders. Their value in fibromyalgia is being evaluated. In preclinical
      behavioural assays they induce effects consistent with anxiolysis, improved
      cognition, anti-dopaminergic activity and use in drug abuse and withdrawal. There
      is some evidence that ondansetron may reduce alcohol consumption in moderate
      alcohol abusers but overall, 5-HT(3) receptor antagonists seem to be of limited
      use in psychiatric disorders: where effects have been seen, they seem to be
      unusually sensitive to dose and stage of disease. Nevertheless, their antiemetic
      potential has been of great benefit to cancer patients and the possible extension
      of their use to bowel disorders may yet fulfil their initial exciting promise.

PMID- 14965243
TI  - 5-HT4 receptors.
AB  - Serotonin 4 receptors (5-HT(4)Rs) were discovered 15 years ago. They are coded by
      a very complex gene (700Kb, 38 exons) which generates eight carboxy-terminal
      variants (a, b, c, d, e, f, g, n). Their sequences differ after position L(358).
      Another variant is characterized by a 14 residue insertion within the
      extracellular loop 2. Highly selective potent 5-HT(4) receptor antagonists and
      partial agonists which cross the blood-brain barrier have been synthesized, but a
      specific full agonist for brain studies is still missing. Based on physiological
      and behavioral experiments, 5-HT(4)Rs may be targets to treat cognitive deficits,
      abdominal pain and feeding disorders. One 5-HT(4)R-directed drug (SL65.0155) is
      already in phase II to treat patients suffering from memory deficits or dementia.

PMID- 14965244
TI  - 5-HT5 receptors.
AB  - The 5-HT(5) receptor family consists of two members designated as 5-HT(5A) and 5
      HT(5B). To date the 5-HT(5A) receptor has been identified in the mouse, rat, and
      human. The 5-HT(5B) receptor also is expressed in the mouse and rat, but not in
      the human where the coding sequence is interrupted by stop codons. Both receptors
      are essentially limited in distribution to the central nervous system (CNS),
      although the 5-HT(5A) receptor has also been found on neurons and neuronal-like
      cells of the carotid body. Within the CNS the 5-HT(5A) receptor shows a
      relatively broad distribution, while the 5-HT(5B) receptor has a very restricted
      distribution. The 5-HT(5A) receptor has been demonstrated to couple to G
      proteins, and the primary coupling appears to be through Gi/o to inhibit adenylyl
      cyclase activity. The 5-HT(5) receptors have not been extensively characterized
      pharmacologically. Both receptors show their highest affinity for LSD, which
      appears to act as a partial agonist at the 5-HT(5A) receptor. Amongst agonist
      like molecules, 5-CT (5-carboxamidotryptamine) also has high affinity and has
      greater potency and affinity at the 5-HT(5A) receptor than does 5-HT itself. Both
      [(125)I]LSD and [(5)H]5-CT have been used as radioligands to study the receptors
      in vitro. Nothing is known about the role of the 5-HT(5B) receptor in vivo. A
      mouse line has been developed where the 5-HT(5A) receptor has been knocked out
      and these animals have been shown to have a diminished response to LSD-induced
      increases in locomotion. The 5-HT(5) receptors remain as two of the least studied
      and understood of the 5-HT receptor subtypes.

PMID- 14965245
TI  - 5-ht6 receptors.
AB  - The 5-hydroxytryptamine(6) (5-ht(6)) was one of the most recent additions to the
      5-HT receptor family, selective antagonists have recently been developed and
      potential functional roles are now becoming apparent. The high affinity of a wide
      range of psychiatric drugs for the 5-ht(6)receptor, together with its almost
      exclusive expression in the CNS, being abundant in limbic and cortical regions,
      has stimulated significant research interest. The 5-ht(6)receptor appears to
      regulate glutamatergic and cholinergic neuronal activity, and increasing evidence
      suggests that it may be involved in the regulation of cognition, feeding and,
      possibly, affective state and seizures. The current article will review all
      aspects of the discovery, genetics, distribution, pharmacology and function of
      the 5-ht(6)receptor. Taken together, this wealth of information warrants the use
      of the upper case nomenclature for the 5-ht(6) receptor to be approved and its
      true status recognised.

PMID- 14965246
TI  - 5-HT7 receptors.
AB  - Following the cloning of the 5-HT(7) receptor in 1993, studies to investigate 5
      HT(7) receptor function in native tissues focused on identifying functional
      correlates that matched the pharmacological profile determined for the cloned
      receptor. Studies in peripheral tissues established that the 5-HT(7) receptor
      mediates the relaxation of smooth muscle, including the gastrointestinal tract
      and cardiovascular systems. Although a number of studies provided preliminary
      evidence for a role for the 5-HT(7) receptor in the circadian pacemaker function
      of the suprachiasmatic nucleus (SCN), additional studies to investigate 5-HT(7)
      receptor function in other brain regions have, until recently, been hindered by
      the absence of 5-HT(7) receptor-selective ligands. More recently, a number of 5
      HT(7) receptor-selective antagonists including, SB-269970-A and SB-656104-A have
      been developed. Studies utilising these compounds suggest that the 5-HT(7)
      receptor modulates neuronal function in a number of brain areas including the
      hippocampus and thalamus. In turn, these findings suggest that 5-HT(7) receptor
      selective ligands might prove therapeutically useful for the treatment of
      psychiatric disorders. In this respect there is increasing evidence to suggest
      that the 5-HT(7) receptor plays a role in the control of both circadian rhythms
      and sleep and might therefore represent a therapeutic target for the treatment of
      those disorders in which disturbances in circadian rhythms and sleep architecture
      are thought to be contributory factors. Furthermore, there is evidence to suggest
      that the receptor may play a role in other CNS disorders including, anxiety,
      cognitive disturbances and also migraine probably via both peripheral and central
      mechanisms. Although further studies are required to confirm the potential role
      of the receptor in such disorders, findings to date suggest there are exciting
      opportunities for the development of novel therapeutic agents acting either
      selectively at the 5-HT(7) receptor or whose profile of action includes an
      interaction with this receptor.

PMID- 14965247
TI  - ATP hydrolysis-dependent multidrug efflux transporter: MDR1/P-glycoprotein.
AB  - P-glycoprotein/MDR1 was the first member of the ATP-binding cassette (ABC)
      transporter superfamily to be identified in a eukaryote. In eukaryotes, ABC
      proteins can be classified into three major groups based on function:
      transporters, regulators, and channels. MDR1/P-glycoprotein is a prominent member
      of eukaryotic export-type ABC proteins. MDR1/P-glycoprotein extrudes a very wide
      array of structurally dissimilar compounds, all lipophilic and ranging in mass
      from approximately 300 to 2000 Da, including cytotoxic drugs that act on
      different intracellular targets, steroid hormones, peptide antibiotics,
      immunosuppressive agents, calcium channel blockers, and others. Nucleotide
      binding and hydrolysis by MDR1/P-glycoprotein is tightly coupled with its
      function, substrate transport. ATP binding and hydrolysis were extensively
      analyzed with the purified MDR1/P-glycoprotein. The vanadate-induced nucleotide
      trapping method was also applied to study the hydrolysis of ATP by MDR1/P
      glycoprotein. When MDR1 hydrolyzes ATP in the presence of excess orthovanadate,
      an analog of inorganic phosphate, it forms a metastable complex after hydrolysis.
      Using this method, MDR1/P-glycoprotein can be specifically photoaffinity-labeled
      in the membrane, if 8-azido-[alpha(32)P]ATP is used as ATP. Visualization of the
      structure, as well as the biochemical data, is needed to fully understand how
      MDR1/P-glycoprotein recognizes such a variety of compounds and how it carries its
      substrates across the membrane using the energy from ATP hydrolysis. To do so,
      large amounts of pure and stable proteins are required. Heterologous expression
      systems, which have been used to express P-glycoprotein, are also described.

PMID- 14965248
TI  - The role of MDR1 genetic polymorphisms in interindividual variability in P
      glycoprotein expression and function.
AB  - The human multidrug resistance gene (MDR1), spanning greater than 200 kb, encodes
      for the ATP-dependent membrane efflux transporter, P-glycoprotein (Pgp).
      Significant progress has been made in the discovery of MDR1 polymorphisms and the
      assessment of allelic frequencies. The search for key genetic determinants that
      predispose individuals to drugs that are substrates or inhibitors of Pgp has just
      begun. Reports in the literature, particularly focusing on the C3435T
      polymorphism, have provided discordant results with respect to functional
      modification in vitro, and Pgp expression and disposition of probe drugs in vivo.
      Due to the large size of the MDR1 gene, genotyping based on individual single
      nucleotide polymorphism (SNPs) analysis is not sufficient to predict functional
      consequences. Strong linkage disequilibrium has been detected between several
      MDR1 polymorphisms, and discrepancies in the literature may be due to the focus
      on the influence of single nucleotide variations instead of on linked nucleotide
      variations. Multiple SNPs found on the same chromosome are assigned to a specific
      haplotype, and some attempts have been made to determine the role of MDR1
      haplotypes in Pgp variability. Most of the data for MDR1 haplotype have been
      predicted based on computational or mathematical models. However, molecular
      haplotyping techniques, analysis of linkages on the same chromosome directly by
      biophysical and biochemical means, may be needed to characterize haplotypes in
      individuals with a highly polymorphic and large gene like MDR1. Haplotype
      identification may prove to be vital in identifying the functional significance
      of MDR1 polymorphisms on disease susceptibility and drug disposition.

PMID- 14965249
TI  - The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate
      specificity and regulation.
AB  - Several members of different families of the ATP-binding cassette (ABC)
      superfamily of transport proteins are capable of transporting an extraordinarily
      structurally diverse array of endo- and xenobiotics and their metabolites across
      cell membranes. Together, these transporters play an important role in the
      absorption, disposition and elimination of these chemicals in the body. In tumor
      cells, increased expression of these drug transporters is associated with
      resistance to multiple chemotherapeutic agents. In this review, current knowledge
      of the biochemical, physiological and pharmacological properties of nine members
      of the multidrug resistance protein (MRP)-related ABCC family (MRP1, MRP2, MRP3,
      MRP4, MRP5, MRP6, MRP7, ABCC11 and ABCC12) as well as the G family member,
      ABCG2/BCRP, are summarized. A focus is placed on the structural similarities and
      differences of these drug transporters as well as the molecular determinants of
      their substrate specificities and transport activities. Factors that regulate
      expression of the MRP-related proteins and ABCG2/BCRP are also reviewed.

PMID- 14965250
TI  - The role of organic ion transporters in drug disposition: an update.
AB  - Transporters for organic anions and organic cations in kidney, liver, intestine,
      brain, and placenta play essential roles in drug disposition. The cloning and
      characterization of these transporters have significantly advanced our
      understanding of the molecular and cellular mechanisms of the drug disposition
      process. This review aims at updating the recent knowledge of general properties,
      structure-function relationships, and regulation mechanisms of the organic anion
      transporters (OATs) and the organic cation transporters (OCTs). Such information
      will be essential for the design and development of new drugs to maximize
      therapeutic efficacy and minimize drug-induced toxicity as well as unwanted drug
      drug interactions.

PMID- 14965251
TI  - Mammalian nucleoside transporters.
AB  - Nucleoside transporters mediate cellular uptake of physiologic nucleosides for
      nucleic acid synthesis in the salvage pathways in many cell types. These
      transporters also play an important role in in vivo disposition and intracellular
      targeting of many nucleoside analogs used in anticancer and antiviral drug
      therapy. In mammalian cells, there are two major nucleoside transporter gene
      families: the equilibrative nucleoside transporters (ENTs) and the concentrative
      nucleoside transporters (CNTs). The ENTs are facilitated carrier proteins and the
      CNTs are Na(+)-dependent secondary active transporters. Recent molecular cloning
      of a number of ENT and CNT transporters has greatly advanced our understanding of
      the molecular and cellular mechanisms by which nucleosides and nucleoside analogs
      are transported across biological membranes. In this manuscript, we review the
      structure, function, tissue distribution, and cellular localization of various
      cloned mammalian nucleoside transporters. Information on transporter interaction
      with various nucleoside drugs and analogs is presented. Current knowledge on the
      regulation of nucleoside transporters in various cell types and tissues is
      reviewed. The therapeutic significance of nucleoside transporters is discussed
      along with emerging data from recent clinical studies.

PMID- 14965252
TI  - Peptide transporters: structure, function, regulation and application for drug
      delivery.
AB  - Proton-coupled peptide transporters, localized at brush-border membranes of
      intestinal and renal epithelial cells, play important roles in protein absorption
      and the conservation of peptide-bound amino nitrogen. These transporters also
      have significant pharmacological and pharmacokinetic relevance to the transport
      of various peptide-like drugs such as beta-lactam antibiotics. The identification
      and molecular characterization of H(+)/peptide cotransporters (PEPT1 and PEPT2)
      have facilitated the clarification of many aspects of these transporters such as
      the structure/function relationship and regulation. Recent findings that
      intestinal PEPT1 can transport l-valine ester prodrugs such as valacyclovir
      provided a major step forward toward the development of novel drug delivery
      systems. It has been demonstrated that peptide transporters, which have a similar
      substrate specificity to PEPT1 and PEPT2, but possess other distinct functional
      properties, are localized at basolateral membranes of intestinal and renal
      epithelial cells. This review highlights the recent advances in our knowledge of
      the cellular and molecular nature of PEPT1, PEPT2 and the basolateral peptide
      transporters.

PMID- 14965253
TI  - Drug transport at the blood-brain barrier and the choroid plexus.
AB  - The blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) represent the main
      interfaces between the central nervous system (CNS) and the peripheral
      circulation. Drug exposure to the CNS is dependent on a variety of factors,
      including the physical barrier presented by the BBB and the BCSFB and the
      affinity of the substrate for specific transport systems located at both of these
      interfaces. It is the aggregate effect of these factors that ultimately
      determines the total CNS exposure, and thus pharmacological efficacy, of a drug
      or drug candidate. This review discusses the anatomical and biochemical barriers
      presented to solute access to the CNS. In particular, the important role played
      by various efflux transporters in the overall barrier function is considered in
      detail, as current literature suggests that efflux transport likely represents a
      key determinant of overall CNS exposure for many substrates. Finally, it is
      important to consider not only the net delivery of the agent to the CNS, but also
      the ability of the agent to access the relevant target site within the CNS.
      Potential approaches to increasing both net CNS and target-site exposure, when
      such exposure is dictated by efflux transport, are considered.

PMID- 14965254
TI  - Intestinal drug transporters: in vivo function and clinical importance.
AB  - The oral route of drug administration remains the most popular and convenient
      route of administration, despite its many shortcomings and challenges. Although
      the advantages associated with this route far outweigh any limitations, a
      prominent limitation relates to the interactions of drugs with intestinal
      membrane transporters. The complexities of these interactions and their impact on
      drug absorption and absorption variability are only now becoming recognized. The
      rapidly growing awareness of transporter-mediated secretion, saturable
      absorption, and even the concerted actions of transporters in intestinal drug
      absorption and secretion has attracted the attention of pharmaceutical scientists
      in academia, the pharmaceutical industry and the regulatory agencies. This is
      evidenced by the recent rapid accumulation of data in the literature, the routine
      conducting of transport studies in the discovery and development of drugs, and
      finally by the recognition of the importance of transporter (e.g. P-glycoprotein
      and OATP) mediated secretion of drugs by regulatory authorities such as the U.S.
      Food and Drug Administration. In this mini-review, we focus on the handful of
      absorptive and secretory transporters that have been relatively well studied and
      illustrate the impact of these intestinal transporters on oral drug absorption
      using published reports from preclinical and clinical studies.

PMID- 14965255
TI  - Placental drug transporters.
AB  - Any treatment of a pregnant woman with medication (drugs) de facto results in the
      treatment of her unborn child, even when her unborn child is not the target of
      drug therapy. This is because, in most instances, the placenta is not a complete
      barrier to the passage of drugs from the maternal to the fetal compartment. This
      barrier is in part due to the presence of various efflux transporters in the
      placenta. The placenta is also richly endowed with influx transporters. In this
      article, we will review the physiological characteristics of the placenta and how
      it functions as a barrier to passage of drugs into the fetal compartment. In
      addition, we will review placental transporters that are important in modulating
      the exposure of the fetus to drugs and, therefore, the efficacy and toxicity of
      such drugs towards the fetus.

PMID- 14965256
TI  - Screening for disease-markers and investigating drug effects by proteome
      profiling: can it meet expectations?
AB  - Drugs exert their functions mainly by affecting proteins. Therefore, it seems
      straightforward to focus on proteins in order to investigate drug effects.
      Unfortunately, proteins are of very high complexity, rendering it much more
      difficult to screen for protein alterations as compared to gene regulation.
      However, the efficiency and applicability of proteome analysis has been
      dramatically increased recently. We are on the way to be able to comprehensively
      assess disease-related proteome alterations, which may become an essential source
      of information for knowledge-based drug design. This review will provide an
      overview of current techniques in proteome analysis, focusing on screening
      technologies for biomedical research. An outlook at the future potential of
      proteomics supported by modern bioinformatics will highlight why proteomics is
      worth the effort.

PMID- 14965257
TI  - Scalable distance similarity of chemical structures.
AB  - Screening a library of molecular graphs for an exact or approximate match with
      one particular molecular graph, the query graph, is reduced to list comparisons.
      The lists contain lengths of shortest paths in graph Voronoi regions. This
      induces the notion of shortest path similarity. All graphs that are shortest path
      similar to the query graph are efficiently retrievable. The same applies to
      approximate or similarity matching. For the retrieval of all superstructures of a
      query, shortest path lists are modified to distance patterns. This also allows
      algorithmic support for query construction.

PMID- 14965258
TI  - On a 3-D representation of DNA primary sequences.
AB  - We introduce a graphical representation of DNA primary sequences by taking four
      special vectors in a 3-D space to represent the four nucleic acid bases in DNA
      sequences, so that a DNA primary sequence is denoted in a 3-D space by a
      successive vector sequence which is a directed walk on the space. It is
      demonstrated that this representation has no overlap and intersection and allows
      numerical characterization.

PMID- 14965259
TI  - High-throughput DNA analysis by microchip electrophoresis.
AB  - DNA analysis plays a great role in genetic and medical research, and clinical
      diagnosis of inherited diseases and particular cancers. Development of new
      methods for high throughput DNA analysis is necessitated with incoming of post
      human genome era. A new powerful analytical technology, called microchip
      capillary electrophoresis (MCE), can be integrated with some experimental units
      and is characterized by high-speed, small sample and reagent requirements and
      high-throughput. This new technology, which has been applied successfully to the
      separation of DNA fragments, analysis of polymerase chain reaction (PCR)
      products, DNA sequencing, and mutation detection, for example, will become an
      attractive alternative to conventional methods such as slab gel electrophoresis,
      Southern blotting and Northern blotting for DNA analysis. This review is focused
      on some basic issues about DNA analysis by MCE, such as fabrication methods for
      microchips, detection system and separation schemes, and several key applications
      are summarized.

PMID- 14965260
TI  - Time-resolved fluorescence measurements using microlens array and area imaging
      devices.
AB  - Time-resolved fluorescence (TRF) assay formats are frequently used technologies
      in high-throughput screening. In this article, we have characterised the novel
      Plate::Vision(2) 96-microlens array reader (Carl Zeiss Jena GmbH, Germany) and
      compared it to the novel LEADseeker Generation IV multimodality imaging system
      (LEADseeker Gen IV; Amersham Biosciences UK Ltd., UK) for applications in the TRF
      mode. In europium measurements using the TRF mode, the Plate::Vision displayed a
      limit of detection for europium of approximately 3 pM, which was comparable to
      two established TRF readers, the Discovery and the Victor V (both PerkinElmer
      Life Sciences Inc., USA). The LEADseeker's limit of detection only extended down
      to europium concentrations of approximately 10 pM in these experiments. For TRF
      resonance energy transfer (TR-FRET) experiments, a europium-biotin (Eu-biotin)
      conjugate was titrated with a streptavidin-allophycocyanin (SA-APC) conjugate.
      The Plate::Vision produced Z' values larger than 0.5 for the acceptor fluorophor
      emission with concentrations of Eu-biotin as low as 3 nM combined with 175 pM SA
      APC. To achieve Z' values of at least 0.5 with the LEADseeker, concentrations of
      10 nM Eu-biotin combined with SA-APC of at least 0.8 nM were required. In a drug
      screening application using TR-FRET, the energy transfer from a europium-labelled
      protein X (Eu-protein X) to a complex of biotinylated peptide Y with SA-APC was
      measured. Using the Plate::Vision, a Z' factor larger than 0.5 for the acceptor
      fluorophor emission was only obtained for a Eu-protein X concentration of at
      least 10 nM in combination with biotinylated peptide Y/SA-APC at saturating
      concentrations. Both the Plate::Vision and the LEADseeker show good quality
      results for applications in the TRF mode and enable an increased throughput based
      on their shortened measurement time in comparison to classic photomultiplier tube
      based readers.

PMID- 14965261
TI  - Accelerated screening of phage-display output with alkaline phosphatase fusions.
AB  - When using multiple targets and libraries, selection of affinity reagents from
      phage-displayed libraries is a relatively time-consuming process. Herein, we
      describe an automation-amenable approach to accelerate the process by using
      alkaline phosphatase (AP) fusion proteins in place of the phage ELISA screening
      and subsequent confirmation steps with purified protein. After two or three
      rounds of affinity selection, the open reading frames that encode the affinity
      selected molecules (i.e., antibody fragments, engineered scaffold proteins,
      combinatorial peptides) are amplified from the phage or phagemid DNA molecules by
      PCR and cloned en masse by a Ligation Independent Cloning (LIC) method into a
      plasmid encoding a highly active variant of E. coli AP. This time-saving process
      identifies affinity reagents that work out of context of the phage and that can
      be used in various downstream enzyme linked binding assays. The utility of this
      approach was demonstrated by analyzing single-chain antibodies (scFvs),
      engineered fibronectin type III domains (FN3), and combinatorial peptides that
      were selected for binding to the Epsin N-terminal Homology (ENTH) domain of epsin
      1, the c-Src SH3 domain, and the appendage domain of the gamma subunit of the
      clathrin adaptor complex, AP-1, respectively.

PMID- 14965262
TI  - Design of a compound screening collection for use in high throughput screening.
AB  - In this paper we introduce a quantitative model that relates chemical structural
      similarity to biological activity, and in particular to the activity of lead
      series of compounds in high-throughput assays. From this model we derive the
      optimal screening collection make up for a given fixed size of screening
      collection, and identify the conditions under which a diverse collection of
      compounds or a collection focusing on particular regions of chemical space are
      appropriate strategies. We derive from the model a diversity function that may be
      used to assess compounds for acquisition or libraries for combinatorial synthesis
      by their ability to complement an existing screening collection. The diversity
      function is linked directly through the model to the goal of more frequent
      discovery of lead series from high-throughput screening. We show how the model
      may also be used to derive relationships between collection size and
      probabilities of lead discovery in high-throughput screening, and to guide the
      judicious application of structural filters.

PMID- 14965263
TI  - Prostate cancer prevention by silibinin.
AB  - Several epigenetic alterations leading to constitutively active mitogenic and
      cell-survival signaling, and loss of apoptotic response are causally involved in
      self-sufficiency of prostate cancer (PCA) cells toward uncontrolled growth, and
      increased secretion of pro-angiogenic factors. Therefore, one targeted approach
      for PCA prevention, growth control and/or treatment could be inhibition of
      epigenetic molecular events involved in PCA growth, progression and angiogenesis.
      In this regard, silibinin/silymarin (silibinin is the major active compound in
      silymarin) has shown promising efficacy. Our extensive studies with
      silibinin/silymarin and PCA cells have shown the pleiotropic anticancer effects
      leading to cell growth inhibition in culture and nude mice. The underlying
      mechanisms of silibinin/silymarin efficacy against PCA involve alteration in cell
      cycle progression, and inhibition of mitogenic and cell survival signaling, such
      as epidermal growth factor receptor, insulin-like growth factor receptor type I
      and nuclear factor kappa B signaling. Silibinin also synergizes the therapeutic
      effects of doxorubicin in PCA cells, making it a strong candidate for combination
      chemotherapy. Silibinin/ silymarin also inhibits the secretion of proangiogenic
      factors from tumor cells, and causes growth inhibition and apoptotic death of
      endothelial cells accompanied by disruption of capillary tube formation on
      Matrigel. More importantly, silibinin inhibits the growth of in vivo advanced
      human prostate tumor xenograft in nude mice. Recently, due to its non-toxic and
      mechanism-based strong preventive/therapeutic efficacy, silibinin has entered in
      phase I clinical trial in prostate cancer patients.

PMID- 14965264
TI  - Apoptosis is a critical cellular event in cancer chemoprevention and chemotherapy
      by selenium compounds.
AB  - Epidemiological studies, preclinical investigations and clinical intervention
      trials support the role of selenium compounds as potent cancer chemopreventive
      agents; the dose and the form of selenium are critical factors in cancer
      prevention. Induction of apoptosis and inhibition of cell proliferation are
      considered important cellular events that can account for the cancer preventive
      effects of selenium. Toxicity should always be considered a determining factor in
      the selection of potential chemopreventive agents. Prior to induction of
      apoptosis, selenium compounds alter the expression and/or activities of a number
      of cell cycle regulatory proteins, signaling molecules, proteases, mitochondrial
      associated factors, transcriptional factors, tumor suppressor genes, polyamine
      and glutathione levels. Depending on the form, selenium compounds can target
      separate pathways but more efforts are needed to learn about disrupting different
      pathways converging to apoptosis. Numerous selenium compounds are known to
      inhibit carcinogenesis in several animal models but not all of these have been
      examined for their efficacy to induce apoptosis or vice versa in the
      corresponding target organ. Studies aimed at investigating the effects of
      selenium compounds on apoptosis in the target organ in vivo and in vitro are
      limited. On the basis of information provided in this review, we recommend that
      additional molecular markers should be added to those proposed in the Selenium
      and Vitamin E Cancer Prevention Trial (SELECT) on prostate cancer. Apart from the
      selenium compounds reviewed here, several novel synthetic organoselenium
      compounds need to be examined both in vitro and in vivo for their potential to
      induce apoptosis; such an investigation may provide better and mechanism-based
      cancer chemoprevention as well as chemotherapeutic agents.

PMID- 14965265
TI  - NSAIDs and chemoprevention.
AB  - Several epidemiological, clinical and experimental studies established
      nonsteroidal anti-inflammatory drugs (NSAIDs) as promising cancer chemopreventive
      agents. Long-term use of aspirin and other NSAIDs has been shown to reduce the
      risk of cancer of the colon and other gastrointestinal organs as well as of
      cancer of the breast, prostate, lung, and skin. Understanding the action of
      NSAIDs provides substantial insights into the mechanisms by which these unique
      agents regulate tumor cell growth and enable better strategies for prevention and
      treatment. NSAIDs restore normal apoptosis and reduce cell proliferation in human
      adenomatous colorectal polyps, experimental colonic tumors, and in various cancer
      cell lines that have lost critical genes required for normal function. NSAIDs,
      particularly selective cyclooxygenase-2 (COX-2) inhibitors such as celecoxib,
      have been shown to inhibit angiogenesis in cell culture and in rodent models of
      angiogenesis. Exploration of the multistep process of carcinogenesis has provided
      substantial insights into the mechanisms by which NSAIDs modulate these events.
      However, unresolved questions with regard to safety, efficacy, optimal treatment
      regimen, and mechanism of action currently limit the clinical application of
      NSAIDs to the prevention of polyposis in FAP patients. Moreover, the development
      of safe and effective NSAIDs for chemoprevention is complicated by the potential
      that rare, serious toxicity may offset the benefit of treatment with these drugs
      given to healthy individuals who have a low risk of developing the disease.
      Growing knowledge in this area has brought about innovative approaches using
      combine actions of NSAIDs with other agents that have different modes of action.
      It has also led to the development of nitric oxide-releasing NSAIDs, that induce
      tumor cell apoptosis and compensate for COX function, as a means of increasing
      efficacy and minimizing toxicity. There is growing optimism for the view that
      full exploration of the role of NSAIDs in the prevention and treatment of
      epithelial cancers will serve towards reducing of mortality and morbidity from
      various cancers.

PMID- 14965266
TI  - Regulation of radiation-induced apoptosis by early growth response-1 gene in
      solid tumors.
AB  - Ionizing radiation exposure is associated with activation of certain immediate
      early genes that function as transcription factors. These include members of jun
      or fos and early growth response (EGR) gene families. In particular, the
      functional role of EGR-1 in radiation-induced signaling is pivotal since the
      promoter of EGR-1 contains radiation inducible CArG DNA sequences. The Egr-1 gene
      belongs to a family of Egr genes that includes EGR-1, EGR-2, EGR-3, EGR-4, EGR
      alpha and the tumor suppressor, Wilms' tumor gene product, WT1. The Egr-1 gene
      product, EGR-1, is a nuclear protein that contains three zinc fingers of the
      C(2)H(2) subtype. The EGR-1 GC-rich consensus target sequence, 5'-GCGT/GGGGCG-3'
      or 5'-TCCT/ACCTCCTCC-3', has been identified in the promoter regions of
      transcription factors, growth factors, receptors, cell cycle regulators and
      proapoptotic genes. The gene targets mediated by Egr-1 in response to ionizing
      radiation include TNF-alpha, p53, Rb and Bax, all these are effectors of
      apoptosis. Based on these targets, Egr-1 is a pivotal gene that initiates early
      signal transduction events in response to ionizing radiation leading to either
      growth arrest or cell death in tumor cells. There are two potential application
      of Egr-1 gene in therapy of cancer. First, the Egr-1 promoter contains
      information for appropriate spatial and temporal expression in-vivo that can be
      regulated by ionizing radiation to control transcription of genes that have pro
      apoptotic and suicidal function. Secondly, EGR-1 protein can eliminate "induced
      radiation resistance" by inhibiting the functions of radiation-induced pro
      survival genes (NFkappaB activity and bcl-2 expression) and activate proapoptotic
      genes (such as bax) to confer a significant radio-sensitizing effect. Together,
      the review of reported findings demonstrate clearly that EGR-1 is an early
      central gene that confers radiation sensitivity and its pro-apoptotic functions
      are synergized by abrogation of induced radiation resistance.

PMID- 14965267
TI  - Stress signaling from irradiated to non-irradiated cells.
AB  - Evidence accumulated over the past two decades has indicated that exposure of
      cell populations to ionizing radiation results in significant biological effects
      occurring in both the irradiated and non-irradiated cells in the population. This
      phenomenon, termed the "bystander response", has been shown to occur both in
      vitro and in vivo. Experiments have indicated that genetic alterations, changes
      in gene expression and lethality occur in bystander cells that neighbor directly
      irradiated cells. Furthermore, cells recipient of growth medium harvested from
      irradiated cultures exhibit responses similar to those of the irradiated cells.
      Several mechanisms involving secreted soluble factors, gap-junction intercellular
      communication and oxidative metabolism have been proposed to regulate the
      radiation-induced bystander effect. In this review, our current knowledge of this
      phenomenon and its potential impact both on the estimation of risks of exposure
      to low doses/low fluences of ionizing radiation and on radiotherapy is discussed.

PMID- 14965268
TI  - A dual role of cyclin E in cell proliferation and apoptosis may provide a target
      for cancer therapy.
AB  - Cyclin E is essential for progression through the G1-phase of the cell cycle and
      initiation of DNA replication by interacting with and activating its catalytic
      partner, the cyclin dependent kinase 2 (Cdk2). Rb, as well as Cdc6, NPAT, and
      nucleophosmin, critical components of cell proliferation and DNA replication,
      respectively, are targets of Cyclin E/Cdk2 phosphorylation. There are a number of
      putative binding sites for E2F in the cyclin E promoter region, suggesting an E2F
      dependent regulation. Skp2 and Fbw7 are novel proteins, responsible for ubiquitin
      dependent proteolysis of Cyclin E. The tight regulation of cyclin E expression,
      both at the transcriptional level and by ubiquitin-mediated proteolysis,
      indicates that it has a major role in the control of the G1- and S-phase
      transitions. Cyclin E is also transcriptionally regulated during radiation
      induced apoptosis of hematopoietic cells. In addition to its biological roles,
      deregulated cyclin E expression has an established role in tumorigenesis. Cell
      cycle regulatory molecules, such as cyclin E, are frequently deregulated in
      different types of cancers, where overexpressed native or low molecular weight
      forms of Cyclin E have a significant role in oncogenesis. During apoptosis of
      hematopoietic cells, caspase-dependent proteolysis of Cyclin E generates a p18
      Cyclin E variant. Understanding the role of Cyclin E in apoptosis may provide a
      novel target, which may be effective in cancer therapy. This review summarizes
      what is known about the biological role of cyclin E, its deregulation in cancer,
      and the opportunities it may provide as a target in clinical therapy.

PMID- 14965269
TI  - Protein kinase CK2 as regulator of cell survival: implications for cancer
      therapy.
AB  - Recent studies have generated sufficient information to warrant a consideration
      of protein kinase CK2 as a potential target for cancer therapy. CK2 is a
      ubiquitous and highly conserved protein serine/threonine kinase that has long
      been considered to play a role in cell growth and proliferation. It is essential
      for cell survival, and considerable evidence suggests that it can also exert
      potent suppression of apoptosis in cells. This is important since the cancer
      phenotype is characterized by deregulation of not only proliferation but also of
      apoptosis. In normal cells, the level of CK2 appears to be tightly regulated, and
      cells resist a change in their intrinsic level of CK2. However, in all the
      cancers that have been examined an elevation of CK2 has been observed. Further,
      it appears that modest deregulation in the CK2 expression imparts a potent
      oncogenic potential to the cells. Disruption of CK2 by treatment of cells with
      antisense CK2 results in induction of apoptosis in a time and dose-dependent
      manner. Thus, we propose that down-regulation of CK2 by employing specific
      strategies to deliver antisense CK2 in vivo could have a potential role in cancer
      therapy.

PMID- 14965270
TI  - Novel targeting of apoptosis pathways for prostate cancer therapy.
AB  - Selection of treatment options for clinically localized prostate cancer is based
      on a host of factors including the patient's age, overall health status,
      potential complications, clinical tumor stage and Gleason score. It is widely
      acknowledged that androgen independent disease remains the main obstacle to
      improving the survival and quality of life in patients with advanced prostate
      cancer. Apoptosis as a genetically regulated process has a critical endpoint that
      coincides with the therapeutic goal of successful treatment of androgen-dependent
      and androgen-independent prostate cancer. Opportunities to alter the apoptotic
      threshold of prostate cancer cells using antisense technology and gene therapy
      certainly exist, but the scope and extent of their applicability and action
      depends upon research delineating the many subtleties within the apoptotic
      pathway. Most epithelial and endothelial cells undergo apoptosis when they loose
      contact with the extracellular matrix (ECM), via the phenomenon of anoikis.
      Signaling interaction between growth factor apoptosis-signaling pathways and
      cellular effectors of anoikis potential and tumor vascularity provides a new
      molecular basis for optimizing combination approaches for the effective treatment
      of advanced prostate cancer. Agents that induce epithelial or endothelial cell
      apoptosis by antagonizing integrin binding are considered for cancer therapy via
      their ability to inhibit tumor vascularization. This review summarizes the
      current knowledge of the therapeutic benefit of apoptosis induction within the
      context of tumor neovascularization inhibition, and provides an insight into the
      consequences of anoikis induction (by different agents) in targeting angiogenesis
      in prostate cancer cells.

PMID- 14965271
TI  - Death receptors as targets of cancer therapeutics.
AB  - To date six bona fide death receptors (DRs) have been discovered and include
      tumor necrosis factor receptor 1 (TNF-R1), Fas, DR3, DR4, DR5 and DR6. Each
      receptor contains an extracellular region and an intracellular region; the
      intracellular region harbors a death domain that is critical for transduction of
      apoptotic signals. These death receptors are activated by their respective
      ligands. For example, TNFalpha activates TNF-R1 while FasL and TL1A activate Fas
      and DR3 respectively. TNF-related apoptosis inducing ligand (TRAIL), also known
      as Apo2L, activates DR4 and DR5. The ligand for DR6 has yet to be identified.
      These death receptors are also believed to be activated in a ligand-independent
      manner. A large body of recent evidence suggests that death receptors could be
      utilized as key molecular targets to develop novel therapeutics. This review
      discusses the pros and cons of targeting death receptors in the development of
      novel cancer therapeutic agents.

PMID- 14965272
TI  - Spectroscopic characterization of Phaseolus vulgaris leucoagglutinin.
AB  - Phaseolus vulgaris leucoagglutinin is a homotetrameric legume lectin possessing
      the canonical dimeric structure common to other legume lectins. In order to gain
      insight into the stability of the protein in an acidic environment, it was
      characterized by CD and fluorescence studies at pH 2.5. This was then compared
      with the native protein at physiological pH (7.2). The extinction coefficient of
      the native protein was calculated to be 3.58x10(4) from its UV absorption
      spectra. The far- and near-UV CD spectra of the protein at pH 2.5 showed very
      little difference even though the protein was found to exist as a dimer at pH
      2.5. The fluorescence emission maxima of the protein upon excitation at 280 nm
      were found to shift only from 331 nm at pH 7.2 to 333 nm at pH 2.5. Based on the
      above observation it was concluded that the protein exhibits extreme pH stability
      especially in the acidic range. The secondary and tertiary structure of the
      protein is lost only when it is incubated for two days in 6 M GdnHCl at pH 2.5.
      At pH 7.2 it could be denatured in 6 M GdnHCl after one week of incubation.

PMID- 14965273
TI  - The primary ligand-binding interaction at the GLP-1 receptor is via the putative
      helix of the peptide agonists.
AB  - The N-terminal domain of the GLP-1 receptor binds the putative helical region of
      the peptide agonists, GLP-1 and exendin-4. Here we demonstrate that this
      interaction also determines the magnitude of a separate interaction between the N
      terminus of these peptides and the receptor's core domain. Enhancing the pre
      formation of the C-terminal Trp-Cage motif of exendin-4, a motif critical for
      high-affinity binding, results in no improvement in receptor affinity, suggesting
      that this motif forms after the initial peptide-receptor binding event.

PMID- 14965274
TI  - Met-204 and Tyr-205 are together important for binding GLP-1 receptor agonists
      but not their N-terminally truncated analogues.
AB  - A mutagenesis study to systematically analyse residues spanning the first
      extracellular loop of the GLP-1 receptor identified a double mutant, Met-204/Tyr
      205-Ala/Ala, which displayed: markedly reduced affinity for the natural agonist
      GLP-1; slightly reduced affinity for its analogue exendin-4; and unaltered
      affinity for several N-terminally truncated analogues of GLP-1 and exendin-4.
      This suggests that the locus is important for the formation of the binding site
      for the N-terminal residues of peptide agonists.

PMID- 14965275
TI  - NMR studies of the prionogenic peptide derived from Sup35 protein.
AB  - The NMR studies of the prionogenic peptide derived from Sup35 are presented. The
      peptide molecules were dissolved in the half-aqueous solution to prevent severe
      aggregation, and were found to be in an extended conformation from the chemical
      shift and the coupling constant data. They could form higher order multimers by
      making intermolecular hydrogen bonds, judging from the observation that the NMR
      sample became a gel-like state at lower temperatures. This work reports the first
      structural information in the solution state about the prionogenic peptide
      mimicking the state of amyloid fibrils, and provides a solid foundation for
      further structural analysis of peptide molecules forming insoluble aggregates.

PMID- 14965276
TI  - Cytosolic insulin-binding proteins of mouse liver cells.
AB  - It has been recently shown that insulin retains its biological activity after
      receptor-directed internalization and it may affect the cell metabolism by
      interaction with cytosolic insulin-binding proteins (CIBPs). Using affinity
      chromatography combined with SDS-PAGE and MALDI-TOF mass-spectrometry we have
      identified 7 proteins from mouse liver cells that specifically bind to the
      insulin, including adenylate kinase 2 (25.6 kD), kinesin superfamily protein 20B
      (26.0 kD), hepatic arginase 1 (34.8 kD), fructose-bisphosphate aldolase B (39.5
      kD), 4-hydroxyphenylpyruvate dioxygenase (45.1 kD), betaine-homocysteine methyl
      transferase (45.0 kD) and KRIT1 (83.4 kD).

PMID- 14965277
TI  - Effects of two glycine residues in positions 13 and 17 of pleurocidin on
      structure and bacterial cell selectivity.
AB  - Pleurocidin (Ple), a 25-residue alpha-helical antimicrobial peptide, isolated
      from skin mucosa of the winter flounder, shows potent bacterial cell selectivity.
      In this study, the effect of two glycine residues in positions 13 and 17 of Ple
      on structure and bacterial cell selectivity was investigated by Gly-->Ala
      substitution. Ala-substitution (Gly(13, 17)-->Ala, Gly13-->Ala and Gly17-->Ala)
      in positions 13 and 17 of Ple did not induce a significant change in
      antibacterial activity, but increased hemolytic activity. Both Gly(13, 17)-->Ala
      and Gly17-->Ala substitution did not cause a remarkable change in alpha-helical
      content in SDS micelles, while Gly(13, 17)-->Ala substitution caused a drastic
      increase in alpha-helical content. These results suggest that the hinge region
      from Gly13 to Gly17 of Ple is assumed to provide its conformational flexibility
      and bacterial cell selectivity.

PMID- 14965278
TI  - Quaternary structure of alpha-crystallin is necessary for the binding of unfolded
      proteins: a surface plasmon resonance study.
AB  - The interactions between an oligomeric heat-shock protein, alpha-crystallin, and
      its individual subunits with unfolded proteins were monitored by surface plasmon
      resonance. Immobilization at the sensor chip allowed us for the first time to
      study isolated alpha-crystallin subunits under physiological conditions. We
      observe that these subunits, in contrast to alpha-crystallin oligomers, do not
      bind unfolded protein. Our data indicate that quaternary structure of alpha
      crystallin is necessary for its chaperone-like activity.

PMID- 14965279
TI  - Expression and secretion of functional recombinant scu-PA:AV in insect cell using
      signal peptides.
AB  - A fusion protein (scu-PA:AV) was expressed in the baculovirus expression system
      and secreted from Sf9 cells lead by signal peptides, 2mel and 3egt. The scu-PA:AV
      displays both the urokinase activity and membrane binding activity of its
      parental components. Our work indicated that it is possible to be developed as a
      thrombus-targeting drug.

PMID- 14965280
TI  - Seed protein variation among pepper (Capsicum sp.) genotypes revealed by MALDI
      TOF analysis.
AB  - A method for seed proteome analysis using MALDI-TOF mass spectrometry is
      described. The data were used to estimate the genetic diversity degree among
      twelve genotypes of pepper (Capsicum). The resulting spectra were converted into
      a binary matrix consisting of 23 protein data sets, and genetic similarity values
      were calculated with the FreeTree software and Jaccard's coefficient of
      similarity. We have also been able to identify the presence of certain proteins
      in the extracts, by checking their masses on on-line databases.

PMID- 14965281
TI  - Expression, purification and characterization of recombinant mouse PC6B from
      baculovirus-infected insect cells.
AB  - We constructed a mouse PC6B truncated mutant and introduced a tag of 6
      consecutive histidines at its carboxyl terminus for simple purification. Using
      the baculovirus expression system and standard enzymatic assay, we obtained
      recombinant mouse PC6B protein and with enzymatic activity.

PMID- 14965282
TI  - Fluorescent modification of N-terminal amino group in peptides for complete
      sequence analysis using PSD method in MALDI-TOF-MS.
AB  - In the sequence analyses of peptides from nucleoprotein in influenza virus, it
      was very difficult to obtain the sufficient numbers of fragment ions using the
      post-source decay (PSD) method in MALDI-TOF-MS. Fluorescent modification of the N
      terminal amino group in the target peptides was introduced for the PSD
      measurement. The fluorescently-labelled peptides gave sufficient fragment ions in
      the PSD spectrum, which leads to the complete sequence analysis of peptide.

PMID- 14965283
TI  - Crystallization and X-ray crystallographic studies of an inhibitor from rye
      (Secale cereale) active against Acanthoscelides obtectus and Zabrotes
      subfasciatus alpha-amylases.
AB  - Crystals of a new inhibitor present in rye seeds active against alpha-amylases
      from crop pests Acanthoscelides obtectus and Zabrotes subfasciatus have been
      obtained. A native dataset was collected at 2.21 A resolution with 99.3%
      completeness at CPr beamline at LNLS. The crystals belong to the trigonal system,
      space group P3(1)21 with a=b=78.21 A, and c=59.61 A. The crystal calculated
      solvent content is compatible with one dimer per asymmetric unit.

PMID- 14965284
TI  - Biophysical characterization of an insect lysozyme from Manduca sexta.
AB  - Insect lysozyme from Manduca sexta (MS-lys) was overexpressed in E. coli and
      refolded to obtain active protein. Recombinant MS-lys presented a globular
      structure, with an alpha-helical content of 57% as assessed by circular dichroism
      spectroscopy. Light scattering studies showed that in solution MS-lys has a quasi
      monodisperse size distribution, with a rod-like structure similar to nucleation
      clusters reported in egg lysozyme pre-crystallization stages. These results show
      that MS-lys is an excellent candidate for crystallization, folding and
      denaturation studies.

PMID- 14965285
TI  - Crystallization and MAD data collection of high-molecular weight cytochrome c
      from Desulfovibrio vulgaris Miyazaki F.
AB  - Hexadecaheme high molecular weight cytochrome c from a sulfate-reducing
      bacterium, Desulfovibrio vulgaris Miyazaki F has been successfully purified and
      crystallized. X-ray diffraction data have been collected by the multiple
      wavelength anomalous dispersion method. The crystal belongs to the space group
      P2(1)2(1)2(1) with unit-cell parameters a=60.42, b=84.29 and c=144.16 A and
      contains one molecule per asymmetric unit.

PMID- 14965286
TI  - Synthesis and structure-activity relationships of 4,10-dihydro-4-oxo-4H
      imidazo[1,2-a]indeno[1,2-e]pyrazine derivatives: highly potent and selective AMPA
      receptor antagonists with in vivo activity.
AB  - The excitatory neurotransmitter glutamate interacts with ionotropic and
      metabotropic receptors that mediate a variety of normal signalling processes in
      the brain. However, excessive stimulation of these receptors appears to be
      involved in neurodegenerative processes, at least in animal models. Ionotropic
      glutamate receptors can be divided into NMDA and non-NMDA (AMPA and KA) subtypes
      on the basis of t heir preferential affinities for the synthetic excitatory amino
      acids N-methyl-D-aspartic acid (NMDA) or 2-amino-3-(3-hydroxy-5-methylisoxazol-4
      yl) propionic acid (AMPA), respectively. Although most of the early evidence
      favoured a role for NMDA receptors in the excitotoxic processes, it has been
      recognised that AMPA receptors may also be significantly involved in neuronal
      death. As a consequence, the synthesis of specific AMPA antagonists has raised
      much interest as source of potential drugs for epilepsy and acute and chronic
      neurodegenerative diseases. The discovery of RPR117824, a potent and selective
      AMPA receptors antagonist endowed with anticonvulsant and neuroprotective
      properties, induced growing interest on dihydro-4-oxo-4H-imidazo[1,2-a]indeno[1,2
      e]pyrazine series. This review covers the main chemical course leading to the
      most promising compounds as well as the pharmacological properties of this
      original class of AMPA receptor antagonists.

PMID- 14965287
TI  - Antiprotozoal lysophospholipid analogues: a comparison of their activity against
      trypanosomatid parasites and tumor cells.
AB  - Lysophospholipid analogues (LPAs), originally developed as anti-cancer agents,
      have shown significant activity against Leishmania spp. and Trypanosoma cruzi,
      both in vitro and in vivo. Miltefosine, used as a topical formulation (Miltex)
      for metastases, was registered in 2002 for the oral treatment of visceral
      leishmaniasis. LPAs interfere with lipid synthesis in T. cruzi and cancer cells,
      but the activity is about >20-fold higher against the parasite.

PMID- 14965288
TI  - Prospects for caspase inhibitors.
AB  - Programmed cell death, or apoptosis, is executed by a series of Cysteine Aspartyl
      Proteases (Caspases) that form a proteolytic cascade. Each caspase functions
      either to activate downstream caspases by proteolytic cleavage and/or to
      proteolytically cleave cellular substrates. Increased levels of apoptosis and
      caspase activity are frequently observed at sites of cellular damage in both
      acute (e.g. myocardial infarction, stroke, sepsis) and chronic (e.g. Alzheimer's,
      Parkinson's and Huntington's Disease) indications. Thus, inhibition of caspase
      activity with the aim of reducing cell death, and hence tissue damage, is
      predicted to be therapeutically beneficial. Herein we outline different
      approaches that have been taken to identify small-molecule caspase inhibitors
      that include both traditional (e.g. HTS, structure-based design and substrate
      analog approaches) and novel screening technologies (e.g. Tethering). In
      addition, the characterization of inhibitors emerging from these programs will
      also be presented. Many of these compounds demonstrate efficacy in a wide range
      of animal models; however, only two examples of caspase inhibitors have
      progressed to clinical testing. Here we will discuss issues (both compound and
      mechanism related) associated with developing a caspase program in the
      pharmaceutical industry.

PMID- 14965289
TI  - Comparison of predictive ability of water solubility QSPR models generated by
      MLR, PLS and ANN methods.
AB  - ADME/Tox computational screening is one of the most hot topics of modern drug
      research. About one half of the potential drug candidates fail because of poor
      ADME/Tox properties. Since the experimental determination of water solubility is
      time-consuming also, reliable computational predictions are needed for the pre
      selection of acceptable "drug-like" compounds from diverse combinatorial
      libraries. Recently many successful attempts were made for predicting water
      solubility of compounds. A comprehensive review of previously developed water
      solubility calculation methods is presented here, followed by the description of
      the solubility prediction method designed and used in our laboratory. We have
      selected carefully 1381 compounds from scientific publications in a unified
      database and used this dataset in the calculations. The externally validated
      models were based on calculated descriptors only. The aim of model optimization
      was to improve repeated evaluations statistics of the predictions and effective
      descriptor scoring functions were used to facilitate quick generation of multiple
      linear regression analysis (MLR), partial least squares method (PLS) and
      artificial neural network (ANN) models with optimal predicting ability. Standard
      error of prediction of the best model generated with ANN (with 39-7-1 network
      structure) was 0.72 in logS units while the cross validated squared correlation
      coefficient (Q(2)) was better than 0.85. These values give a good chance for
      successful pre-selection of screening compounds from virtual libraries, based on
      the predicted water solubility.

PMID- 14965290
TI  - Biomedical applications of chemically and microbiologically synthesized
      poly(glutamic acid) and poly(lysine).
AB  - This review article deals with the synthesis, physiochemical properties, and
      potential biomedical applications of two homo-poly amino acids. Poly-alpha
      glutamic acid (alpha-PGA) and poly-alpha-lysine (alpha-PL) were synthesized by
      chemical synthesis. poly-gamma-glutamic acid (gamma-PGA) and poly-epsilon-lysine
      (epsilon-PL) were naturally occurring bio-materials that were produced by
      microbial fermentation. Poly(glutamic acid) (PGA) and poly(lysine) (PL) are water
      soluble, biodegradable, edible and nontoxic toward humans and the environment. As
      a result, they are suitable for various applications and have recently attracted
      considerable interest of the chemical industry. The distinguished features of PGA
      and PL also make them promising candidates for biomedical applications. The
      applications of PGA and PL in the areas of biomedical materials, drug delivery
      carriers and biological adhesives have been studied extensively and will be
      discussed in this review.

PMID- 14965291
TI  - Antiviral sulfonamide derivatives.
AB  - The sulfonamides constitute an important class of drugs, with several types of
      pharmacological agents possessing antibacterial, anti-carbonic anhydrase,
      diuretic, hypoglycemic, antithyroid and anticancer activity among others. A large
      number of structurally novel sulfonamide derivatives have ultimately been
      reported to show substantial antiviral activity in vitro and in vivo. The review
      summarizes recent classes of sulfonamides and related sulfonyl derivatives
      disclosed as effective such agents. Thus, at least some HIV protease inhibitors
      used clinically (amprenavir) or compounds in advanced clinical trials
      (tipranavir, TMC-126, TMC-114, etc.) possess sulfonamide moieties in their
      molecules, whereas a very large number of other derivatives are constantly being
      synthesized and evaluated in order to obtain compounds with less toxicity or
      activity against drug-resistant viruses. Several non nucleoside HIV reverse
      transcriptase or HIV integrase inhibitors containing sulfonamide groups were also
      reported. Another approach to inhibit the growth of retroviruses, including HIV,
      targets the ejection of zinc ions from critical zinc finger viral proteins, which
      has as a consequence the inhibition of viral replication in the absence of
      mutations leading to drug resistance phenotypes. Most compounds with antiviral
      activity possessing this mechanism of action incorporate in their molecules
      primary sulfonamide groups. Finally, some small molecule chemokine antagonists
      acting as HIV entry inhibitors also possess sulfonamide functionalities in their
      scaffold.

PMID- 14965292
TI  - Anti-Helicobacter pylori agents. An update.
AB  - Helicobacter pylori infection is the major causative factor of a number of
      gastric pathologies. Several classes of compounds have been identified as anti-H.
      pylori agents. Here we provide a review of anti-H. pylori compounds that have
      recently appeared in the literature, including the guanidino, antibiotics,
      acetamide, pyrazole and benzimidazole compounds.

PMID- 14965293
TI  - Synthetic approaches to the 2002 new drugs.
AB  - New drugs are introduced to the market every year and each individual drug
      represents a privileged structure for its biological target. In addition, these
      new chemical entities (NCEs) not only provide insights into molecular
      recognition, but also serve as drug-like leads for designing future new drugs.
      Therefore, it is important to be acquainted with these new structures as well as
      their syntheses. To these ends, this review covers the syntheses of 28 NCEs
      marketed in 2002.

PMID- 14965294
TI  - Facts, figures and trends in lead generation.
AB  - The goal of this paper is to review the variety of approaches adopted to improve
      lead generation, and make the process easier for the chemist, faster and more
      likely to succeed in later phases of drug development. Our analysis shows that
      successful lead generation requires not only an accurate definition of the needs
      (to define the most relevant assay protocols and readouts), but most of all a
      good hit as a starting point. It also appears that teams where techniques are
      combined are more successful in that difficult game.

PMID- 14965295
TI  - The design of screening libraries targeted at G-protein coupled receptors.
AB  - The screening of large libraries in order to obtain hits for receptors of
      interest has been the mainstay of drug research for some time now. It is
      increasingly being recognised that this is a relatively inefficient way to
      achieve this end and the screening of libraries either designed or selected to
      hit particular targets is rapidly becoming the method of choice. The advantages
      in terms of success rate to achieve viable lead series are magnified by the cost
      and time savings achieved by screening more carefully selected groups of
      compounds. A number of approaches have been used for the design and production of
      such libraries or methods for selection of such focused sets from larger diverse
      collections. These range from combinatorially produced ligand-mimetic approaches
      through pharmacophore-based design to those methods based on statistical
      selection techniques. Most recently, progress in chemogenomic approaches has
      thrown new light on the relationship between receptor sequence and compounds that
      interact at particular receptors and this is also having an impact on the design
      of targeted libraries.

PMID- 14965296
TI  - Molecular similarity and property similarity.
AB  - This paper reviews the main efforts undertaken up to date in order to understand,
      rationalize and apply the similarity principle (similar compounds=>similar
      properties) as a computational tool in modern drug discovery. The best suited
      mathematical expression of this classical working hypothesis of medicinal
      chemistry needs to be carefully chosen (out of the virtually infinite possible
      implementations in terms of molecular descriptors and molecular similarity
      metrics), in order to achieve an optimal validation of the hypothesis that
      molecules that are neighbors in the Structural Space will also display similar
      properties. This overview will show why no single "absolute" measure of molecular
      similarity can be conceived, and why molecular similarity scores should be
      considered tunable tools that need to be adapted to each problem to solve.

PMID- 14965297
TI  - "It's the chemistry, stupid!", or: The impact of early discovery patent
      applications on the drug development process.

PMID- 14965298
TI  - Recent developments in the synthesis of nicotinic acetylcholine receptor ligands.
AB  - The extraordinary pharmacology of nicotine and epibatidine have indicated the
      potential for nicotinic acetylcholine receptor (nAChR) ligands to serve as a new
      therapeutic class for a host of CNS disorders. Many such ligands are natural
      products, or analogs thereof, which represent a significant challenge to the
      synthetic chemist. Synthesis of such molecules often serves as a showcase to
      demonstrate the potential of newly developed methodology. This synthetic
      challenge coupled with the promise of pharmacological activity in compounds
      possessing the nicotinic pharmacophore has stimulated a great deal of synthetic
      activity over the last five years. The present report provides an overview of
      novel synthetic methodology occurring during this period directed toward the
      synthesis of compounds with presumed affinity for the neuronal nAChR. Syntheses
      chosen for review here represent the major efforts toward molecules such as
      epibatidine analogs, anatoxin-a, nicotine and related alkaloids, conformationally
      constrained nicotine derivatives, cytisine and methyllycaconitine (MLA).

PMID- 14965299
TI  - Musings on alpha4beta2 nicotinic acetylcholine (nACh) receptor pharmacophore
      models.
AB  - Several pharmacophore models were previously formulated to account for the
      actions of nicotinic acetylcholinergic (nACh) agents. Most of these models were
      developed without express consideration of specific radioligand binding data
      because such data were not available at the time the models were described. In
      this review, the ability of these models to account for the binding of nicotinic
      agents at alpha4beta2 nACh receptors (or rat brain receptors for which
      alpha4beta2 receptors are the major component) is assessed. It seems that none of
      the early models can adequately explain the binding of these agents as a group.
      Furthermore, different series of nicotinic agents behave differently depending
      upon the nature of terminal amine substituents and the spacer that separates the
      amine from the pyridine ring. A region of bulk tolerance has been identified that
      accommodates substituents on some nicotinic ligands, but not the same
      substituents at seemingly corresponding locations of others. The concept of
      multiple modes of binding has been previously raised and, clearly, cannot yet be
      discarded. Nevertheless, new vector models seemingly provide a better picture of
      nACh receptor binding and account for many of the shortcomings associated with
      the earlier models.

PMID- 14965300
TI  - Rational understanding of nicotinic receptors drug binding.
AB  - The atomic determination of the acetylcholine binding protein (AChBP), a
      molluscan cholinergic protein, homologous to the amino-terminal extracellular
      domain of nicotinic receptors (nAChRs), offers opportunities for the modeling of
      the acetylcholine binding site and its ligands. Recently, we constructed three
      dimensional models of the N-terminal part of nAChR and docked in the putative
      ligand-binding pocket, different agonists (acetylcholine, nicotine and
      epibatidine) and antagonist (snake alpha-bungarotoxin). These hypothetical
      docking models offer a structural basis for rational design of drugs
      differentially binding to resting and active (or desensitized) conformations of
      the receptor site. These models thus pave the way to investigate, at the
      molecular level, the exciting challenge of the fast ion channel gating mechanisms
      by nicotinic agonists.

PMID- 14965301
TI  - Molecules of infectious agents as immunomodulatory drugs.
AB  - Microbes produce a wide range of molecules that can modulate eukaryotic immune
      responses. These include factors that subvert protective mechanisms in order to
      facilitate pathogen colonization and persistence. Viral, bacterial and parasite
      derived molecules have been identified that can inhibit inflammatory responses.
      However, in addition to the plethora of microbial factors that suppress immune
      responses, the most potent immune activators are also of microbial origin. These
      include the bacterial enterotoxins, parasite-derived excretory-secretory products
      and viral nucleic acids. In fact, there are examples of immune modulators that
      can exert either stimulatory or suppressive effects depending on the mode of
      delivery, dose and experimental model. There is presently great interest in the
      therapeutic exploitation of these factors, for example as a means to stimulate
      enhanced immune responses to a new generation of subunit vaccines or to inhibit
      deleterious immune mediated diseases. This short review, describes representative
      microbial immunomodulators, their modes of action and the potential for
      therapeutic application.

PMID- 14965302
TI  - Modulation of the immune response by the cholera-like enterotoxins.
AB  - Cholera toxins and heat labile enterotoxin from E. coli differ from most soluble
      proteins in eliciting systemic immunity both against themselves and unrelated
      admixed antigens, rather than tolerance following administration to a mucosal
      surface. Several reports have also demonstrated preferential induction of Th2
      type responses when these molecules are used as adjuvants. Conversely, these
      proteins and their non-toxic derivatives, including the B sub-units are also able
      prevent and alleviate autoimmune diseases in naive and systemically immune hosts
      demonstrating wide-ranging effects on the immune system. The recent observation
      that amelioration of autoimmune disease is associated with the generation of
      regulatory T cells which inhibit pathogenic Th1 responses may also help to
      consolidate these two apparently contradictory outcomes of exposure to the
      cholera-like enterotoxins. Furthermore, the observation that EtxB is able to
      alleviate autoimmune disease in the absence of conjugation to autoantigen
      highlights its potential for use in the clinical setting where the target antigen
      is often unknown. Direct effects on T cells, B cells and APC have been
      demonstrated in vitro which have provided insights into how these molecules may
      elicit these diverse effects. Further investigation is required for elucidation
      of the mechanisms of action of adjuvanticity and tolerance induction by these
      molecules to realise their potential for use in vaccines and therapies for
      autoimmune disease in humans.

PMID- 14965303
TI  - The impact of infection on the incidence of autoimmune disease.
AB  - Falling infection rates in the developed world are being matched by a rapidly
      rising incidence of allergic and autoimmune diseases. This review explores the
      hypothesis that there is a causal link between these phenomena and that
      infections can prevent the onset of autoimmune disease. The hypothesis is
      discussed with particular reference to Type I diabetes in the NOD mouse and the
      ability of the helminth infection Schistosoma mansoni to prevent its onset. The
      article addresses the possible mechanisms that underly this protection. The
      effects of protective pathogen-derived agents on key cells of the innate immune
      system such as dendritic cells are distinct and include the production of anti
      inflammatory cytokines such as IL-10. The most likely mechanisms by which these
      innate changes prevent the subsequent adaptive autoimmune destruction are: (1)
      the production of systemically high levels of cytokines that oppose the
      production of cytokines that drive the autoimmune process - possibly via the
      action of natural killer T (NKT) cells (2) the induction of regulatory T cells
      that inhibit the action of autoreactive cells and (3) the production of pathogen
      specific T cells that are not autoreactive and compete with autoreactive cells
      for survival signals such as cytokines and T cell receptor ligation.

PMID- 14965304
TI  - Th1-mediated pathology in mouse models of human disease is ameliorated by
      concurrent Th2 responses to parasite antigens.
AB  - Epidemiologic evidence strongly suggests that improved standards of living are
      associated with an increased incidence of immune system-mediated disease.
      Allergy, autoimmunity, and within the focus of our laboratory, idiopathic
      inflammatory bowel disease, most notably Crohn's disease and ulcerative colitis,
      and progression of chronic gastritis to gastric cancer, are all mediated by
      proinflammatory immune responses induced by known or unknown antigens. A popular
      theory, known as the 'hygiene hypothesis' (1), suggests that improved health
      standards achieved through sanitation and vaccination, may in part be responsible
      for the apparent increase in immune system-mediated disease due to decreasing
      microbial and parasitic infections in humans, particularly in children. As
      antigenic exposure of children to infectious agents, especially parasites, has
      rapidly decreased, it is suspected that normally protective counter-regulatory
      Th2-type immune responses fail to develop, increasing the risk for aberrant pro
      inflammatory responses in otherwise genetically pre-disposed individuals. This
      hypothesis has stimulated significant interest in development of animal models of
      Th1- and Th2-mediated disease to test this paradigm. This review illustrates some
      of the exciting evidence that Th1-mediated pathology in mouse models of
      helicobacter disease and diabetes is ameliorated by concurrent anti-inflammatory
      Th2 responses to parasite antigens and that initial application of these
      principles is benefiting human patients. The results from developing animal
      models of human disease not only support the hygiene hypothesis but also have led
      to novel therapies using parasite antigens to stimulate anti-inflammatory Th2
      type responses to restore homeostasis in patients with aberrant Th1-type immune
      mediated disease.

PMID- 14965305
TI  - Molecules of parasites as immunomodulatory drugs.
AB  - Parasite molecules offer unique advantages for the treatment of immunologicical
      disorders, and several candidate molecules have been shown to be effective. In
      our studies, it was shown that a factor inducing immunoglobulin E from filarial
      nematode parasites was suppressive in animal models of immunological disorders
      such as allergy and insulin dependent diabetes mellitus (IDDM). The Th1/Th2
      paradigm of CD4+ T helper cell subsets can provide the basis for the development
      of new types of drugs and of novel strategies for the treatment of allergic and
      autoimmune disorders by parasite molecules. In our experimental system, parasite
      molecules from a filarial nematode parasite led to the down-regulation of the
      allergic reaction in animal models. In the majority of hosts, infection with
      helminths is associated with markedly reduced cellular immune reactions and
      polarization of T cell responses to Th2 and Th3 types. Some studies have
      suggested that the stimulation of host immunoregulatory networks with parasite
      molecules leading to the synthesis of anti-inflammatory cytokines (interleukin10,
      transforming growth factor-beta (TGF-beta and others) can provide new therapy for
      immunological disorders. It is known that parasites produce some types of
      molecule that mimic host molecules such as CD40 ligand, TGF-beta and macrophage
      migration inhibitory factor. These molecules are also candidates for medicinal
      agents. This review describes many of the latest possibilities in this field and
      shows how they can be best put to use for the development of medicinal agents,
      molecular target identification, and for prioritization.

PMID- 14965306
TI  - The anti-inflammatory potential of the filarial nematode secreted product, ES-62.
AB  - Filarial nematodes achieve long-term infection via modulation of the host immune
      system. Although human infection can result in severe pathology, the majority of
      infected individuals exhibit little evidence of this. Analysis of the immune
      response during infection indicates that the apparently healthy majority have an
      anti-inflammatory phenotype and it has been speculated that this may contribute
      to maintenance of host health. Recent data suggest that parasite-derived
      molecular secretions contribute to the anti-inflammatory phenotype and we have
      thus characterised a major filarial nematode secreted glycoprotein, ES-62. This
      molecule has been found to possess broad immunomodulatory activities that are in
      general, anti-inflammatory. It has long been recognised that several autoimmune
      disorders including rheumatoid arthritis (RA) exhibit reduced incidence and
      severity in geographic regions in which filarial nematodes are endemic.
      Furthermore, it has been speculated that these two observations are causally
      linked. However, molecular explanations for such an association have not been
      forthcoming. Although the aetiology of RA is unknown most data suggest that it is
      mediated via a pro-inflammatory immune response associated with excess cytokine
      production. Given that ES-62 is anti-inflammatory, we hypothesised that it might
      possess activity against diseases like RA. Indeed we found that subcutaneous
      injection of ES-62 prevented initiation of collagen-induced arthritis (CIA) and
      also suppressed progression of established disease. Ex vivo analyses demonstrated
      that these effects were due to inhibition of TNF-alpha production and reversal of
      collagen specific TH-1 responses. The nematode product was also found to inhibit
      pro-inflammatory cytokine release in vitro in synovial cells derived from RA
      patients. ES-62 thus represents a parasite-derived immunomodulator with
      significant therapeutic potential.

PMID- 14965307
TI  - NKT cell-stimulating synthetic glycolipids as potential therapeutics for
      autoimmune disease.
AB  - Although T cells were previously believed to recognize only peptide antigen
      associated with the major histocompatibility complex (MHC), recent studies have
      shown that there are unique T cells specialized for recognition of lipid or
      glycolipid antigens bound to the MHC class I-like CD1 molecules (CD1a, b, c or
      d). Among these lipid-specific T cells, CD1d-restricted T cells, also referred to
      as natural killer (NK) T cells, are of special interest as a target of drug
      development, since their role in immunoregulation has been indicated in various
      physiological or disease conditions including autoimmunity. They are unique in
      their homogeneous ligand specificity for alpha-glycosylated sphingolipid and
      secrete large amounts of regulatory cytokines shortly after T cell receptor (TCR)
      engagement. The first glycolipid identified as an NKT cell ligand was alpha
      galactosylceramide (alpha-GalCer) derived from marine sponges. alpha-GalCer
      exhibits significant immunomodulatory effects by stimulating NKT cells. However,
      we found that an altered analogue of alpha-GalCer with a shorter sphingosine
      chain (OCH), is more useful than alpha-GalCer for treatment of autoimmune disease
      models, because of its ability to selectively induce IL-4, a key cytokine for
      control of autoimmunity. As such, altered glycolipid ligands (AGL) of alpha
      GalCer appear to be promising reagents for treatment of human autoimmune
      diseases.

PMID- 14965308
TI  - Conformation and bioactivity. Design and discovery of novel antihypertensive
      drugs.
AB  - Peptidomimitism is applied to the medicinal chemistry in order to synthesize
      drugs that devoid of the disadvantages of peptides. AT1 antagonists constitute a
      new generation of drugs for the treatment of hypertension designed and
      synthesized to mimic the C-terminal segment of Angiotensin II and to block its
      binding action on AT1 receptor. An effort was made to understand the molecular
      basis of hypertension by studying the conformational analysis of Ang II and its
      derivatives as well as the AT1 antagonists belonging to SARTANs class of
      molecules. Such studies offer the possibility to reveal the stereoelectronic
      factors responsible for bioactivity of AT1 antagonists and to design and
      synthesize new analogs. An example will be given which proves that drugs with
      better pharmacological and financial profiles may arise based on this rational
      design.

PMID- 14965309
TI  - Structural features of angiotensin-I converting enzyme catalytic sites:
      conformational studies in solution, homology models and comparison with other
      zinc metallopeptidases.
AB  - Angiotensin-I Converting Enzyme (ACE) is a Zinc Metallopeptidase of which the
      three-dimensional structure was unknown until recently, when the X-ray structure
      of testis isoform (C-terminal domain of somatic) was determined. ACE plays an
      important role in the regulation of blood pressure due to its action in the frame
      of the Renin-Angiotensin System. Efforts for the specific inhibition of the
      catalytic function of this enzyme have been made on the basis of the X-ray
      structures of other enzymes with analogous efficacy in the hydrolytic cleavage of
      peptide substrate terminal fragments. Angiotensin-I Converting Enzyme bears the
      sequence and topology characteristics of the well-known gluzincins, a sub-family
      of zincins metallopeptidases and these similarities are exploited in order to
      reveal common structural elements among these enzymes. 3D homology models are
      also built using the X-ray structure of Thermolysin as template and peptide
      models that represent the amino acid sequence of the ACE's two catalytic, zinc
      containing sites are designed and synthesized. Conformational analysis of the
      zinc-free and zinc-bound peptides through high resolution 1H NMR Spectroscopy
      provides new insights into the solution structure of ACE catalytic centers.
      Structural properties of these peptides could provide valuable information
      towards the design and preparation of new potent ACE inhibitors.

PMID- 14965310
TI  - On the structural basis of the hypertensive properties of angiotensin II: a
      solved mystery or a controversial issue?
AB  - Angiotensin II (AII), Asp1-Arg2-Val3-Tyr4-Ile5-His6-Pro7-Phe8, the primary active
      hormone of the Renin-Angiotensin-System (RAS), is a major vasoconstrictor
      implicated in the cause of hypertension. To unravel the question of the
      biologically active conformation(s) of this flexible peptide hormone and to
      better understand the stereoelectronic requirements that lead to the molecular
      basis of hypertension, we will analyze research efforts in the identification of
      pharmacophoric groups of AII and three general approaches for structural
      characterisation: the free peptide-ligand approach, the receptor based approach,
      and approaches that target the peptide-receptor complex. The free peptide-ligand
      based approach can be further categorized to: (a) conformational analysis of AII
      and linear peptide analogues in aqueous solution; (b) the use of solvents of
      medium dielectric constants; (c) conformationally restricted analogues, with
      emphasis to cyclic analogues; (d) the use of receptor-simulating environments,
      and (e) non-peptide mimetics. The receptor and peptide-receptor based approaches
      can be categorised to: (a) The use of monoclonal antibodies and (b) the generic
      description of AII receptor sites through homology modelling and mutagenesis
      studies. These investigations, with particular emphasis to recent developments,
      have greatly assisted in the identification of pharmacophoric groups for receptor
      activation and the development of several models of AII-receptor complexes.

PMID- 14965311
TI  - Efforts to understand the molecular basis of hypertension through drug:membrane
      interactions.
AB  - Biological membranes play an essential role in the drug action. They constitute
      the first barrier for drugs to exert their biological action. AT1 antagonists are
      amphiphilic molecules and are hypothesized to act on AT1 receptor through
      incorporation (first step) and lateral diffusion through membrane bilayers
      (second step). Various biophysical methods along with Molecular Modelling were
      applied in order to explore the plausible two step proposed mechanism of action
      for this class of antihypertensive drugs.

PMID- 14965312
TI  - Simulating physiology and methods for therapeutic evaluation with emphasis on
      hypertension.
AB  - Improvements in therapy are aimed at better diagnosis and more effective
      treatment. The use of computer simulation has the potential to improve therapy in
      both ways. Computational methods have been used extensively in diagnosis, for
      interpreting MRI results, CAT scans and the development of treatments in the
      study of biochemical structure. The present review examines how simulation may be
      used to play a more fundamental role in therapeutic treatment often referred to
      as In Silico Biology. Simulation of cells, organs and systems, such as pulmonary
      and cardiovascular, can be used in clinical practice to improve diagnosis.
      Initially these developments will probably have to be refined before being used
      in general practice. However, when these simulations are linked with artificial
      intelligence techniques containing experimental databases then very powerful
      tools will result. The use of simulation in the design and development of new
      drugs can both be cost and time effective. Again, artificial intelligence
      techniques are likely to play an important role in evaluating patient risk
      factors and unwanted side effects.

PMID- 14965313
TI  - Renin-angiotensin system blockade at the level of the angiotensin converting
      enzyme or the angiotensin type-1 receptor: similarities and differences.
AB  - The development of drugs which block the renin-angiotensin system (RAS) has been
      proven a major advance in cardiovascular medicine. Angiotensin converting enzyme
      (ACE) inhibitors, which block the formation of angiotensin II from the inactive
      angiotensin I, are widely used as first line treatment in hypertension, heart
      failure and diabetic nephropathy. More recently, selective antagonists of the
      angiotensin type-1 receptor (AT1R) have become available for clinical use.
      Accumulating evidence suggests that AT1R antagonists have similar effects to ACE
      inhibitors in hypertension, heart failure and diabetic nephropathy. Although ACE
      inhibitors and AT1R antagonists block the same system, experimental evidence
      suggest that their mechanisms of action differ in several respects, such as
      increased bradykinin and angiotensin 1-7 levels with ACE inhibitors and AT2R
      activation with AT1R antagonists. Nevertheless, the clinical significance of
      these differences remains largely unknown and, in practice, the only clear
      advantage of AT1R antagonists over ACE inhibitors is the absence of cough as a
      side effect. Recent clinical data suggest that combined ACE inhibition and AT1R
      antagonism offer additive effects in reducing blood pressure in hypertension, in
      reducing proteinuria in nephropathy and in improving prognosis in heart failure.
      Further evidence suggests that some hypertensive patients may have a good
      antihypertensive response with ACE inhibition but not with AT1R antagonism, or
      the reverse. These data suggest that these two drug classes have important
      similarities, because they act on the same system, but they also appear to have
      important differences, which are not only of theoretical but also of clinical
      importance.

PMID- 14965314
TI  - Hematocrit-lowering effect following inactivation of renin-angiotensin system
      with angiotensin converting enzyme inhibitors and angiotensin receptor blockers.
AB  - Several clinical and experimental observations suggest that an intact and
      activated renin-angiotensin system (RAS) may be an important determinant of
      erythropoiesis in a variety of clinical conditions, including hypertension,
      chronic renal insufficiency or failure, chronic obstructive pulmonary disease,
      and congestive heart failure. Accordingly, RAS inactivation may confer
      susceptibility to the hematocrit-lowering effects of angiotensin-converting
      enzyme inhibitors or angiotensin receptor blockers. Indeed, a dose-dependent
      decrease in hematocrit is observed within the first month of such therapy. In the
      majority of patients with hypertension decreases in hematocrit values after RAS
      inactivation are small and not clinically important. In extreme conditions,
      however, such as erythrocytosis after successful renal transplantation, secondary
      polycythemia of chronically hypoxemic COPD patients, erythrocytosis associated
      with renovascular hypertension, severe cardiac or renal failure, the hematocrit
      lowering effect of angiotensin-converting enzyme inhibitors and angiotensin
      receptor blocker may be profound and even lead to or worsen anemia. Hematocrit
      reaches its nadir value within three months, and then it remains stable during
      long-term observations. After discontinuation of RAS blockade, hematocrit values
      rise gradually over the next three to four months towards the pretreatment
      levels. The mechanism(s) related to this phenomenon is not yet fully understood,
      but angiotensin II seems to be responsible for inappropriately sustaining
      secretion of erythropoietin despite hematocrit elevation and capable to directly
      stimulate the erythroid progenitors in bone marrow to produce erythrocytes.

PMID- 14965315
TI  - The shift in the "paradigm" of the pharmacology of hypertension.
AB  - Until recently elevated blood pressure was considered as a hemodynamic entity
      representing an increase in workload for the heart and the arterial tree. Control
      of hypertension meant hemodynamic unloading, through inhibition of
      vasoconstrictor pathways, principally renin-angiotensin system and sympathetic
      system. In recent years however a new pharmacological approach has evolved as a
      result of (i) the dissociation of endothelial dysfunction and vascular pathology
      from increased blood pressure; (ii) the recognition that endothelial dysfunction
      regards not only the vascular reactivity, but also promotes atherosclerosis and
      thrombosis; and (iii) an improved understanding of the complexity of local-tissue
      renin angiotensin system and of the vasodilatory and cytoprotective role of
      natriuretic peptides. This has led to a reconsideration of existing medicines in
      terms of specification on endothelial function, more rationalized application of
      drugs and search for new compounds targeting both vasodilatory and anti
      proliferative pathways. Examples include beta1-adrenergic antagonists, such as
      Nebivolol and Carvedilol, and vasopeptidase inhibitors, such as Omapatrilat, that
      inhibit simultaneously the angiotensin converting enzyme and neutral
      endopeptidase. Furthermore the identification of genetic polymorphisms in the
      effectors involved in the pathophysiology of hypertension or in the response to
      anti-hypertensive drugs, such as the p22phox subunit of NADPH oxidase, alpha
      adducin or adrenergic receptors, has promoted the prospective of both better
      understanding of hypertension and individualized strategies for its treatment.

PMID- 14965316
TI  - Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a
      novel allosteric paradigm.
AB  - During the course of infection, a subset of HIV-1 proteins interacts with
      multiple cellular partners, sometimes in a hierarchical or sequential way. These
      proteins include those associated with the initial infection event, with the
      preparation of the cell for the replicative cycle of the virus and with the exit
      of new virions from the infected cell. It appears that the interactions of viral
      proteins with multiple cellular partners are mediated by the occurrence of ligand
      induced conformational changes that direct the binding of these proteins to
      subsequent partners. Two of the most studied HIV-1 proteins that are known to
      interact with different cellular partners are gp120 and Nef. Here we discuss the
      interactions of these two proteins with their cellular partners and present new
      results indicating that the conformational changes undergone by these proteins
      define a novel allosteric paradigm. In the traditional view, conformational
      changes are thought to occur between well defined structural conformations of a
      protein. In gp120 and Nef, those changes involve conformations characterized by
      the presence of large regions devoid of stable secondary or tertiary structure.
      Those unstructured regions contain the binding determinants for subsequent
      partners and only become functionally competent by ligand-induced structuring or
      un-structuring of those regions. By switching binding epitopes between structured
      and unstructured conformations the binding affinity can be modulated by several
      orders of magnitude, thus effectively precluding binding against unwanted
      partners. A better understanding of these interactions would lead to improved
      strategies for inhibitor design against these viral targets.

PMID- 14965317
TI  - Relaxin: new functions for an old peptide.
AB  - The peptide relaxin (RLX) was one of the first hormones to be described with a
      specific function in parturition. In the past ten years, there has been a
      revaluation of RLX physiology and the concept that sex hormones play roles that
      are limited to reproductive functions is rapidly changing. In this view, growing
      evidence indicates that the peptide hormone RLX, structurally related to insulin
      and insulin-like growth factor and primarily secreted by the corpus luteum during
      pregnancy, besides well demonstrated actions on reproductive tissues, is involved
      in a variety of functions. Among them, RLX influences the brain and regulates
      pituitary hormone secretion, causes renal vasodilatation, increases coronary
      flow, exerts chronotropic action on the heart and affects gastrointestinal motor
      responses. Recent studies suggest that in several smooth muscles the hormone
      appears to act by promoting the biosynthesis of nitric oxide (NO), whose altered
      production may be involved in smooth muscle dysmotilities. The recent cloning of
      the RLX receptors and studies on their possible signal transduction mechanisms
      are stimulating researchers to further investigate the effects of this hormone
      and its mechanism of action. This may lead to the discovery of agonists and
      antagonists for RLX and the development of new therapeutic approaches in some
      human diseases. The aim of this mini-review is to summarize the most recent
      findings on the multiple actions of RLX hoping to bring a contribution for the
      future perspectives in this field.

PMID- 14965318
TI  - Binding sites of amyloid beta-peptide in cell plasma membrane and implications
      for Alzheimer's disease.
AB  - The binding of amyloid beta peptides (Abeta) to plasma membranes appears to be a
      promising point of intervention in the events leading to the development of
      Alzheimer's disease (AD). This binding has been studied as regards the direct
      toxicity of Abeta on neurons, and the activation of a local inflammation phase
      involving microglia. By virtue of its structure, Abeta is able to bind to a
      variety of biomolecules, including lipids, proteoglycans and proteins. This
      review focuses on the membrane proteins that can mediate the interaction between
      Abeta and the plasma membranes in AD. On neurons, these are APP (amyloid
      precursor protein), the NMDA-R (N-methyl-D-aspartate receptor), integrins, the
      alpha7nicotinic acetylcholine receptor (alpha7nAChR), the P75 neurotrophin
      receptor (P75NTR) and the CLAC-P/collagen type XXV (collagen-like Alzheimer
      amyloid plaque component precursor/collagen XXV). On glial cells, FPRL1 (formyl
      peptide receptor-like 1), the scavenger receptors A, BI (SR-A, SR-BI) and CD36, a
      complex involving CD36, alpha(6)beta(1)-integrin and CD47, and heparan sulfate
      proteoglycans have been reported to bind Abeta. It should be noted that
      integrins, RAGE (receptor for advanced glycosylation end-products), the Serpin
      enzyme complex receptor (SEC-R) and the insulin receptor can bind Abeta and are
      present on neurons and on glial cells. After a presentation of the structure and
      the function of each of these proteins, the method used to prove their binding to
      Abeta is described, and the implication of this binding in AD is discussed.
      Finally, it is underlined that multireceptor complexes containing integrins may
      be involved in this interaction.

PMID- 14965319
TI  - Cross bridging proteins in nature and their utilization in bio- and
      nanotechnology.
AB  - Cross-linking and cross-bridging are highly versatile methods of creating
      composite protein structures with desired mechanical properties such as
      deformation endurance, elasticity, extensibility, and stability under intensive
      and repetitive sheering forces. Cross-linking and cross-bridging are
      distinguished by the bonds that hold the structural components together. Cross
      linking implies a covalent association, whereas cross-bridging depends on
      biological recognition, in which hydrogen bonding, ionic, and hydrophobic
      interactions predominate. Cross-bridged structures are found in all living
      systems. Cytoskeletal interaction, cell invasion by pathogens, fertilization, and
      cellulosomal degradation of cellulose are all examples of biological processes in
      which cross-bridging proteins play a key role. This article will review the
      different types of biological cross-bridging proteins that are known and discuss
      their emerging nano- and biotechnological applications.

PMID- 14965320
TI  - Glucagon-like peptide 2 (GLP-2), an intestinotrophic mediator.
AB  - Glucagon-like peptide 2 (GLP-2) is a newly discovered gastrointestinal peptide
      with 33% sequence homology to glucagon. GLP-2 has attracted interest because of
      its potent intestinotrophic endocrine/paracrine actions. The peptide, consisting
      of 33-amino-acid, results from expression of the glucagon gene in the
      enteroendocrine L-cells of the intestinal mucosa, from where it is released
      mainly in response to luminal contact with unabsorbed nutrients. In addition to
      mucosal growth, GLP-2 enhances activities of several intestinal brush-border
      enzymes, and it delays gastric transit, thereby increasing the intestinal
      capacity for nutrient absorption. Thus, it appears that GLP-2 serves to ensure an
      optimal intestinal capacity. The physiological responses following exogenous
      administration of GLP-2 have been intensely investigated, and these appear to be
      rather specific for the gut, which is concordant with the localization of the GLP
      2 receptor. In addition, treatment with GLP-2 in experimental animal models of
      several enteropathies indicates that GLP-2 ameliorates most of the observed
      intestinal abnormalities in these conditions. Following secretion to the blood
      stream, the intact peptide is degraded rather rapidly by an aminopeptidase. To
      circumvent the rapid and widespread metabolization of intact GLP-2, degradation
      resistant synthetic GLP-2 analogues have been developed together with other
      approaches, such as inhibition of the GLP-2 degrading enzyme. This is of
      particular interest with respect to developing GLP-2 into a useful therapeutic
      agent in conditions with compromised intestinal function, since the first
      clinical trial has already indicated the potential of GLP-2 treatment in patients
      with short bowel syndrome.

PMID- 14965321
TI  - Cyclooxygenase enzymes: regulation and function.
AB  - The cyclooxygenase isoenzymes, COX-1 and COX-2, catalyze the formation of
      prostaglandins, thromboxane, and levuloglandins. The prostaglandins are autocoid
      mediators that affect virtually all known physiological and pathological
      processes via their reversible interaction with G-protein coupled membrane
      receptors. The levuloglandins are a newer class of products that appear to act
      via irreversible, covalent attachment to numerous proteins. COX enzymes are
      clinically important because they are inhibited by aspirin and numerous other non
      steroidal anti-inflammatory drugs. This inhibition of COX confers relief from
      inflammatory, pyretic, thrombotic, neurodegenerative and oncological maladies.
      About one hundred years have elapsed since Hoffman designed and synthesized
      acetylsalicylic (aspirin) as an agent intended to lessen the gastrointestinal
      irritation of salicylates while maintaining their efficacy. During the past forty
      years systematic advances in our understanding of the structure, regulation and
      function of COX isoenzymes have enabled the design and synthesis of COX-2
      selective inhibitors as agents intended to lessen the gastrointestinal irritation
      of aspirin and non-selective NSAIDs. This review discusses: 1) how two separate
      catalytic processes in COX - peroxidase and prostaglandin synthase - act in an
      integrated fashion manner to generate prostaglandins; 2) why irreversible
      inactivation of COX is important constitutively and pharmacologically; 3) how
      cells have managed to use two closely related, almost identical enzymes in ways
      that discriminate their physiological versus pathological roles; 4) how
      investigators have used these advances to formulate and test medically important
      uses for old drugs (i.e. aspirin) and create new ones that still seek to achieve
      Hoffman's original goal.

PMID- 14965322
TI  - Clinical pharmacology of novel selective COX-2 inhibitors.
AB  - Novel coxibs (i.e. etoricoxib, valdecoxib, parecoxib and lumiracoxib) with
      enhanced biochemical cyclooxygenase (COX)-2 selectivity over that of rofecoxib
      and celecoxib have been recently developed. They have the potential advantage to
      spare COX-1 activity, thus reducing gastrointestinal toxicity, even when
      administered at high doses to improve efficacy. They are characterized by
      different pharmacodynamic and pharmacokinetics features. The higher biochemical
      selectivity of valdecoxib than celecoxib, evidenced in vitro, may be clinically
      relevant leading to an improved gastrointestinal safety. Interestingly,
      parecoxib, a pro-drug of valdecoxib, is the only injectable coxib. Etoricoxib
      shows only a slightly improved COX-2 selectivity than rofecoxib, a highly
      selective COX-2 inhibitor that has been reported to halve the incidence of
      serious gastrointestinal toxicity compared to nonselective nonsteroidal
      antiinflammatory drugs (NSAIDs). Lumiracoxib, the most selective COX-2 inhibitor
      in vitro, is the only acidic coxib. The hypothesis that this chemical property
      may lead to an increased and persistent drug accumulation in inflammatory sites
      and consequently to an improved clinical efficacy, however, remains to be
      verified. Several randomized clinical studies suggest that the novel coxibs have
      comparable efficacy to nonselective NSAIDs in the treatment of osteoarthritis,
      rheumatoid arthritis and acute pain, but they share similar renal side-effects.
      The apparent dose-dependence of renal toxicity may limit the use of higher doses
      of the novel coxibs for improved efficacy. Large-size randomized clinical trials
      are ongoing to define the gastrointestinal and cardiovascular safety of the novel
      coxibs.

PMID- 14965323
TI  - Cardiovascular and renovascular implications of COX-2 inhibition.
AB  - A group of chemical mediators, the eicosanoids, is critical players in a
      multitude of physiological processes. Generated by the action of the
      cyclooxygenase (COX) enzyme on arachidonic acid they are responsible for diverse
      and often opposing actions such as platelet function, vasomotor tone, gastric
      cytoprotection and inflammation. Since their discovery several decades ago, our
      knowledge concerning their synthesis, function as natural ligands and methods to
      manipulate their activity through drug development has expanded. Traditional Non
      Steroidal Anti-Inflammatory Drugs (NSAIDs) are nonselective inhibitors of the COX
      enzyme, of which two isoforms are known to exist - COX-1 and COX-2. NSAIDs have
      been the mainstay of treatment in the management of pain and inflammation
      associated with acute and chronic inflammatory conditions that affect more than
      10 million Americans. Their efficacy in this regard is not questioned. However,
      gastrointestinal toxicity arising from chronic NSAID ingestion is common and
      limits their use in clinical practice. Gastrointestinal toxicity has been
      attributed to the blockade of the COX-1 mediated generation of the cytoprotective
      prostanoids, such as PGE(2) and PGI(2). Selective COX-2 inhibitors were designed
      to inhibit the production of COX-2 dependent inflammatory prostanoids and to
      leave intact the cytoprotective COX-1 products. The first of a new class of these
      selective COX-2 inhibitors - the coxibs- were introduced to the market in 1999.
      These compounds, while exhibiting similar efficacy to traditional NSAIDs, were
      associated with a reduced incidence of surrogate or actual indices of GI
      toxicity. Questions have been raised concerning the cardiovascular and renal
      profiles of these agents based on data from both small and large clinical
      studies. More recently, our increasing understanding of the relative
      contributions of both isoforms of the COX enzyme to individual components of
      vascular homeostais has allowed us to appreciate the cardiovascular and
      renovascular implications of selective COX-2 inhibition.

PMID- 14965324
TI  - Renal COX-2, cytokines and 20-HETE: tubular and vascular mechanisms.
AB  - Our initial studies on renal cyclooxygenase (COX)-2 expression and activity
      addressed the critical role of angiotensin II (Ang II) in increasing tumor
      necrosis factor alpha (TNF) that eventuated in expression of COX-2 in the
      medullary thick ascending limb (mTAL) of the nephron. COX-2 supplanted the
      dominant oxygenase, the cytochrome P450 (CYP) enzyme, omega-hydroxylase, that
      synthesized 20-hydroxyeicosatetraenoic acid (20-HETE). These findings served as
      the basis for additional studies on: 1) the role of glucocorticoids in regulating
      COX-2 expression and activity in the mTAL; and 2) the utilization of the same
      signaling pathways in response to stimulation of the mTAL calcium receptor (CaR).
      These studies of mTAL COX-2 expression which are addressed in the first part of
      this chapter are followed by explorations of the expression of COX-2 in
      preglomerular microvessels (PGMV) and the relationship of COX-2 to 20-HETE, the
      principal eicosanoid of PGMV. The third and last component of this chapter
      explores the signaling events, focusing on COX-2, which are set in motion by
      diabetes.

PMID- 14965325
TI  - Cancer and cyclooxygenase-2 (COX-2) inhibition.
AB  - Prior to the discovery of cyclooxygenase-2 (COX-2), a beneficial association was
      shown between chronic usage of non steroidal anti-inflammatory drugs (NSAIDs),
      that non-selectively inhibit both cyclooxygenase-1 (COX-1) and COX-2, and
      prevention of colorectal cancer. The cloning of COX-2 allowed the development of
      enzyme inhibitors that selectively inhibit COX-2 and also facilitated the
      expression profiling of COX-2 in many cancer tissues. COX-2 selective inhibitors
      have shown efficacy in vitro and in vivo in several animal cancer models and in
      limited human clinical trials. The potency of COX-2 inhibitors in vivo can be
      attributed to the inhibition of the enzyme in the tumor as well as in stromal
      cells, resulting in reduction of carcinogen production, anti-proliferative and
      pro-apoptopic actions within the tumor and anti-angiogenic and pro-immune
      surveillance activities in endothelial and myeloid cells. The combination of COX
      2 inhibitor with standard cancer chemotherapeutic and/or radiation may provide
      additional therapeutic paradigms in the treatment of various human cancers.

PMID- 14965326
TI  - Dysregulated post-transcriptional control of COX-2 gene expression in cancer.
AB  - The cyclooxygenase-2 (COX-2) enzyme catalyzes the rate-limiting step of
      prostaglandin formation in pathogenic states. The molecular regulation of COX-2
      gene expression is normally tightly regulated on transcriptional and post
      transcriptional levels. However, loss of function at either level of COX-2 gene
      regulation promotes constitutive COX-2 overexpression which plays a key role in
      carcinogenesis, particularly colorectal tumorigenesis. Current work investigating
      the regulatory mechanisms of COX-2 expression has demonstrated post
      transcriptional regulation to play a central role. Rapid COX-2 mRNA decay and
      translational inhibition is mediated through a conserved AU-rich element (ARE)
      present within the 3'-untranslated region (3'UTR). The COX-2 ARE exerts its
      control through association with ARE RNA-binding proteins. These trans-acting
      regulatory factors influence the fate of COX-2 mRNA by controlling mRNA
      degradation, stabilization, or translation. Recent evidence demonstrates the
      functional significance rapid mRNA decay and translational inhibition play in
      controlling COX-2 gene expression and that, if dysregulated, allow for
      overexpression of COX-2 and other associated angiogenic factors detected in
      neoplasia.

PMID- 14965327
TI  - Cyclooxygenase-2: potential role in regulation of drug efflux and multidrug
      resistance phenotype.
AB  - Multidrug resistance (MDR) of cancer cells to cytostatic agents is the major
      obstacle for the succesfull chemotherapy. One of the causes of the development of
      cellular resistance to a wide variety of drugs is the elevated expression of
      membrane transporter proteins such as members of ATP binding cassette (ABC)
      protein superfamily. Expression of the ABC transporter MDR1, also termed P
      glycoprotein (P-gp), seems to correlate with drug resistance of tumors to
      chemotherapy. Cyclooxygenase-2, an inducible isoform of enzyme, responsible for
      generation of prostaglandins from arachidonic acid, is constitutively expressed
      in a number of cancer cells. Anti-cancer potency of cyclooxygenase inhibitors is
      established, but the mechanism of Cox-2-dependent potentiation of tumor growth is
      a subject of intense discussion. Here we focus on the discussion of potential
      link between Cox-2 expression and development of multidrug resistance phenotype.
      Our observation, that enforced expression of Cox-2 causes enhancement in MDR1
      expression and functional activity suggests the existence of causal link between
      Cox-2 activity and MDR1 expression. The use of Cox-2 inhibitors to decrease
      function of MDR1 may enhance accumulation of chemotherapy agents and decrease
      resistance of tumors to chemotherapeutic drugs.

PMID- 14965328
TI  - Oxidative metabolism of endocannabinoids by COX-2.
AB  - The last decade has witnessed a rapid expansion in our understanding of the
      mammalian endogenous cannabinoid system. In just a few short years since the
      discovery of endogenous lipids that serve as cannabinoids in vivo, these
      molecules have been shown to participate in a broad array of physiological and
      pathological processes. Consequently, attention has been directed at defining the
      proteins responsible for endocannabinoid synthesis, transport, and metabolism.
      Recently, multiple fatty acid oxygenases including, most notably, cyclooxygenase
      2 (COX-2), have been implicated in endocannabinoid metabolism. This review will
      highlight connections between COX-2 and the endogenous cannabinoid system. The
      available biochemical evidence supporting a role for COX-2 in endocannabinoid
      metabolism will be presented. Finally, the potential biological consequences of
      COX-2-mediated endocannabinoid oxygenation will be discussed.

PMID- 14965329
TI  - Possibility of non-immunosuppressive immunophilin ligands as potential
      therapeutic agents for Parkinson's disease.
AB  - Non-immunosuppressive immunophilin ligands (NI-IPLs) are attracting attention as
      new candidate drugs for neuroprotection and/or neurorestoration, particularly
      since they do not have the adverse effects of immunosuppressants. However, it is
      not yet enough to understand that NI-IPLs are useful drugs for treating
      neurological disorders. In particular, the molecular mechanism of NI-IPL activity
      in target cells in the brain remains obscure. In this review, we focused on the
      molecular basis of the neuroprotective properties of IPLs. Our findings suggest
      that IPLs have neuroprotective effects mediated by multiple beneficial properties
      such as a glutathione (GSH)-activating effect, a neurotrophic factor (NTF)
      activating effect, and an anti-apoptotic effect, but not by an immunosuppressive
      effect, both in cell cultures and in vivo. In particular, the GSH-activating
      effect and the NTF-activating effect of NI-IPLs may be essential to the
      expression of their neuroprotective properties. Thus, NI-IPLs might have a
      potentially beneficial effect by ameliorating neurological disorders, since they
      do not cause serious side effects such as immune deficiency.

PMID- 14965330
TI  - Minocycline: neuroprotective mechanisms in Parkinson's disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder characterized by
      cardinal features of tremor, bradykinesia, rigidity and postural instability. In
      addition to the motor symptoms patients experience cognitive decline eventually
      resulting in severe disability. Pathologically PD is characterized by
      neurodegeneration in the substantia nigra pars compacta (SNc) with
      intracytoplasmic inclusions known as Lewy bodies. In addition to the SNc there is
      neurodegeneration in other areas including cerebral cortex, raphe nuclei, locus
      ceruleus, nucleus basalis of meynert, cranial nerves and autonomic nervous
      system. Recent evidence supports the role of inflammation in Parkinson's disease.
      Apoptosis has been shown to be one of the pathways of cell death in PD.
      Minocycline, a tetracycline derivative is a caspase inhibitor, and also inhibits
      the inducible nitric oxide synthase which are important for apoptotic cell death.
      Furthermore, Minocycline has been shown to block microglial activation of 6
      hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned
      parkinsonism animal models and protect against nigrostriatal dopaminergic
      neurodegeneration. In this review, we present the current experimental evidence
      for the potential use of tetracycline derivative, minocycline, as a
      neuroprotective agent in PD.

PMID- 14965331
TI  - Novel therapeutic effects of the anti-convulsant, zonisamide, on Parkinson's
      disease.
AB  - We found that zonisamide (ZNS) has beneficial effects on Parkinson's disease
      (PD). ZNS is originally synthesized in Japan and has been used for over 10 years
      to treat intractable epilepsy. We administered 300 mg of ZNS to a patient with PD
      who incidentally had convulsive attacks. The attacks disappeared and,
      surprisingly, the parkinsonian symptoms improved dramatically. An open trial of
      ZNS (given in addition to their anti-PD drugs) in advanced PD patients clearly
      showed the lessening of symptoms, especially wearing-off. Although the effects
      gradually decreased after 1.5 years, more than 30% improvement of UPDRS total
      score was maintained up to 3 years. Nation-wide double-blind controlled study
      confirmed that the small dose (50mg/day) of ZNS improved all the cardinal
      symptoms of PD. As for its mechanism, we showed that ZNS increases dopamine
      contents in the striatum by activating dopamine synthesis and the level of mRNA
      of tyrosine hydroxylase (TH) prior to that of TH protein. ZNS moderately inhibits
      monoamine oxydase (MAO) B. It has no effects on dopamine receptors, dopamine
      transporter or dopamine release. ZNS has no direct effects on glutamate
      receptors, adenosine receptors, or serotonergic system, which have been suggested
      to be effective points of anti-PD drug other than dopamine system. Therefore, it
      is suggested that the activation of dopamine synthesis and the moderate level of
      MAOB inhibition are main mechanisms of ZNS effects on PD. ZNS has significant
      effects on T-type Ca(++) channels and oxidative stress. They may also affect the
      beneficial action of ZNS on PD.

PMID- 14965332
TI  - Neuroprotective effects of nonsteroidal anti-inflammatory drugs on
      neurodegenerative diseases.
AB  - It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) possess anti
      inflammatory, analgesic and antipyretic properties by inhibiting cyclooxygenase
      (COX), a prostaglandin-synthesizing enzyme. It has also been revealed that NSAIDs
      exert inhibitory effects on the generating system of nitric oxide radicals and
      modulating effects on transcription factors which are related to inflammatory
      reactions including cytokine expression. Recently, a number of studies have been
      conducted focusing on the neuroprotective effects of NSAIDs, since it has been
      reported that inflammatory processes are associated with the pathogenesis of
      several neurodegenerative diseases including Alzheimer's disease and Parkinson's
      disease. In the experimental model of Parkinson's disease, NSAIDs have also
      exerted neuroprotective effects which are based not only on their COX-inhibiting
      effects but also on other properties: inhibitory effects on nitric oxide
      synthesis, action as agonists for peroxisome proliferator-activated receptor
      gamma, and some unknown pharmacological effects. In this article, various
      pharmacological effects of NSAIDs except their inhibitory action on COX are
      reviewed, and possible neuroprotective effects of NSAIDs have been discussed on
      neurodegenerative diseases, especially Parkinson's disease.

PMID- 14965333
TI  - A mechanistic overview on male infertility and germ cell cancers.
AB  - The testis is devoted to two important tasks: haploid cell production and sexual
      steroid synthesis. A number of highly sophisticated and unique strategies operate
      during spermatogenesis, a process crucial for reproduction, heredity and
      evolution. It is particularly important to decipher the underlying molecular
      mechanisms whose function can be perverted in pathological situations, such as
      infertility and testicular cancers, which represent an increasing biomedical
      issue today. This review summarises the currently available data concerning some
      key molecular components that are altered or potentially involved in male
      infertility and testicular tumors, with the aim of defining some common "hot
      spots". We particularly focused on genetically engineered in vivo models in which
      testicular functions are altered and we pinpointed to the potential involvement
      of the targeted genes in testicular pathologies. Those molecular mechanisms
      peculiar to the male gonad can be envisioned as a basis for the design of novel
      drugs potentially dedicated to testicular dysfunction.

PMID- 14965334
TI  - Molecular genetics of human male infertility: from genes to new therapeutic
      perspectives.
AB  - Genetic lesions causing human male infertility are manifold. Besides gross
      chromosomal aneuploidies and rearrangements, microdeletions and single gene
      defects can interfere with male fertility. Male fertility is not only dependent
      on genes controlling the male germ line but also on genes of the networks
      functional for male gonad development and male somatic development, respectively.
      It is popular to unravel these netweorks with mouse gene knock-out mutants
      displaying reproductive defects. However, substantial arguments can be given for
      more functional studies directly on the human genes, because multiple
      reproductive proteins evolve quickly most likely for adopting to the specific
      needs of the species class. Prominent examples are mutations of the FSHR gene
      causing different pathologies in mouse and human and the DAZ gene family not
      found in the mouse genome but in the human genome with an essential male
      fertility function. Therefore this review is focussed on a comprehensive overview
      of human genes known with mutations causing male infertility (AR; AZF gene
      families; CFTR, DM-1, DNAH gene family, FGFR1, FSHR, INSL3, KAL-1, LGR8- GREAT,
      LHR, POLG). Then some human genes are described well recognised as functional in
      spermatogenesis and male fertility although gene specific mutations causing
      infertility were not yet identified (CREM, CDY1, DAZL1, PHGPx, PRM-1, PRM-2).
      They are designated as "spermatogenesis phase marker" or "male fertility index"
      genes, because they are useful tools for diagnosing the patient's spermatogenesis
      disruption phase and for predicting the presence and quality of his mature
      sperms. Current therapeutic protocols for human male infertility do usually not
      cure the specific gene defect but try to bypass it using Artificial Reproductive
      Technology (ART). Putative imprinting defects in the early embryo probably
      associated with the used ART protocol and an increase of chromosome abnormalities
      in the ART offspring now strongly asks for a significant improvement of this
      outcome requesting urgently more basic research on the genes functioning in the
      human male germ line and during early human embryogenesis.

PMID- 14965335
TI  - Alterations of sex differentiation in males: from candidate genes to diagnosis
      and treatments.
AB  - Sex, that is, whether one is physically male or female, is the basic dichotomy of
      life. Sex is important not only for reproductive role, but also for physical
      attributes, personal identity and disease susceptibility. Sex determination is
      genetically controlled, with the key event in males being the transmission of a Y
      chromosome from father to offspring. The sex-determining gene on the Y
      chromosome, SRY, triggers the expression of a repertoire of other genes that
      cause the undifferentiated gonad to develop as a testis. Hormones secreted by the
      developing testis cause the internal and external genitalia to masculinize.
      Testicular development is disrupted by de novo or inherited genetic alterations
      leading to gonadal dysgenesis. Decreased hormone production from dysgenetic
      testes disrupts the normal development of the internal and external genitalia.
      Incomplete masculinization of the genitalia also occurs from hormonal
      biosynthetic defects or decreased response to hormones from inherited receptor
      defects. Treatment is tailored to the individual diagnosis and may include
      removal of dysgenetic gonads, surgical correction of incompletely masculinized
      genitalia, replacement of deficient hormones, and, in some instances, gender
      reassignment.

PMID- 14965336
TI  - New features in the treatment of androgen-independent prostate cancer.
AB  - Prostate cancer develops from clones that are already present as early as thirty
      five years of age, when circulating concentrations of androgens are high. The
      progression of the disease is low and the cancer is diagnosed at a more advanced
      age. Prostate cancer evolves from an androgen dependant stage to stage where it
      escapes from all anti-androgenic treatments. The patient usually dies within two
      years following the diagnosis of advanced cancer. Therefore, it is of great
      interest to develop new therapies for androgen independent prostate cancer. The
      androgen independent evolution of prostate cancer is a complex phenomenon at the
      cellular and molecular levels. It includes an increased sensitivity to growth
      factors, the control of proliferation pathways, apoptotic and survival pathways
      as well as the control of angiogenesis. Epidemiological studies have also
      suggested that certain vitamins or phyto-oestrogens could protect against
      prostate cancer development. The present review attempts to present an overview
      of the fundamental research in cellular signalling which could be interesting as
      target for the treatment of androgen independent prostate cancer. Also the
      potential interest of non-androgenic steroids was reviewed for the same goal.

PMID- 14965337
TI  - Molecular therapy intervention prospects in prostate cancer.
AB  - Prostate cancer is the most frequently diagnosed disease in American men today
      and the second leading cause of death among them. Transformation and progression
      towards malignancy in prostate cancer is dependant on the inability of the
      prostatic epithelial cells to undergo apoptosis rather than on the regulation of
      proliferation. Molecular targeting of inadequacies in this process of suppression
      of apoptosis could prove to be of great therapeutic importance for prostate
      cancer patients. Existence of tissue specific promoters to aid in the delivery of
      genes with therapeutic potential makes molecular therapy an attractive option.
      This review discusses salient features of molecules such as, Bcl-2, Bcl-(XL), NF
      kappaB, Akt, PTEN and Par-4 that play a significant role in the regulation of
      prostate cancer and focuses on the prospects of effectively utilizing their
      potential for the therapy of hormone-sensitive and hormone-resistant prostate
      cancer.

PMID- 14965338
TI  - Targeting gene therapy for prostate cancer.
AB  - Gene therapy is rapidly emerging as a viable clinical strategy to treat prostate
      cancer. New developments, such as targeted expression of therapeutic genes, and
      viruses that are designed to selectively replicate in prostate cancer cells have
      led to vectors with improved safety, even in elderly male patients. This review
      describes the various different viral and non-viral strategies employed to date,
      with a summary of current clinical trials. The main focus of the review is a
      discussion of the need, and the potential methods that can be used for targeted
      expression of the therapeutic gene specifically to prostate tumours and
      metastases. This includes methods of abrogating vector transduction of non
      specific tissues, enhancement of transduction into prostate tumour tissue,
      transcriptional control of the therapeutic gene and some examples of prostate
      cancer-specific therapeutic genes. We also consider the future of prostate cancer
      gene therapy and the factors that should be taken into account when designing
      clinical trials, in a field that is expected to impact on clinical management of
      a common tumour type.

PMID- 14965339
TI  - Viruses in semen and male genital tissues--consequences for the reproductive
      system and therapeutic perspectives.
AB  - Sexually transmissible diseases such as AIDS have renewed the attention paid to
      viruses capable of infecting the male genital tract. The presence of viruses at
      this level may not only lead to their transmission and spread via semen but may
      also impact on male fertility and/or represent a potential cause of genital organ
      cancers. This review summarizes the currently available data on the various
      viruses identified in the human semen and male reproductive tract, their
      distribution in tissues and fluids, their possible cell targets and the
      functional consequences of their infectivity on the reproductive and endocrine
      systems. The use of medically assisted reproduction as a therapeutic tool in
      serodiscordant couples, as well as treatment strategies that need to be developed
      in order to eradicate these viruses from the male genital tract, are discussed.

PMID- 14965340
TI  - Serum levels of endostatin, vascular endothelial growth factor (VEGF) and
      hepatocyte growth factor (HGF) in patients with acute myocardial infarction
      undergoing early reperfusion therapy.
AB  - Angiogenesis is controlled by anti-angiogenic factors as well as by angiogenic
      factors, such as VEGF (vascular endothelial growth factor) and HGF (hepatocyte
      growth factor). Endostatin, a potent endogenous angiogenesis inhibitor, is known
      to inhibit endothelial proliferation and suppress tumour growth. However, to
      date, little is known about the pathophysiology of endostatin in
      ischaemia/reperfusion. To investigate the mechanisms of angiogenesis induced by
      myocardial ischaemia/reperfusion in more detail, we studied the circulating
      levels of endostatin, VEGF and HGF in 17 patients with acute myocardial
      infarction, who underwent early reperfusion therapy. In all patients, serum
      endostatin, VEGF and HGF levels before reperfusion were increased significantly
      compared with those in 17 control subjects (endostatin, 49.2+/-11.7 ng/ml, but
      not detectable in controls; VEGF, 685.6+/-150.3 pg/ml compared with 173.7+/-33.6
      pg/ml; HGF, 3638+/-1285 pg/ml compared with 59+/-13 pg/ml; values are means+/
      S.E.M.). After reperfusion, the serum endostatin and VEGF levels decreased
      significantly, but still remained higher than those in control subjects
      (endostatin, 19.6+/-7.0 ng/ml; VEGF, 284.2+/-90.2 pg/ml). In contrast, serum HGF
      levels increased significantly (15 146+/-2230 pg/ml) after reperfusion. These
      data indicated that serum levels of endostatin changed in parallel with those of
      VEGF in response to myocardial ischaemia/reperfusion, and the marked increase in
      serum HGF levels after reperfusion seemed to be, at least in part, due to heparin
      administration. Our data offer a possible anti-endostatin therapy in patients
      with acute myocardial infarction to facilitate collateral vessel formation.

PMID- 14965341
TI  - Cloning, tissue distribution, pharmacology and three-dimensional modelling of
      melanocortin receptors 4 and 5 in rainbow trout suggest close evolutionary
      relationship of these subtypes.
AB  - The rainbow trout (Oncorhynchus mykiss) is one of the most widely used fish
      species in aquaculture and physiological research. In the present paper, we
      report the first cloning, 3D (three-dimensional) modelling, pharmacological
      characterization and tissue distribution of two melanocortin (MC) receptors in
      rainbow trout. Phylogenetic analysis indicates that these receptors are
      orthologues of the human MC4 and MC5 receptors. We created 3D molecular models of
      these rainbow trout receptors and their human counterparts. These models suggest
      greater divergence between the two human receptors than between their rainbow
      trout counterparts. The pharmacological analyses demonstrated that ACTH
      (adrenocorticotropic hormone) had surprisingly high affinity for the rainbow
      trout MC4 and MC5 receptors, whereas alpha-, beta- and gamma-MSH (melanocyte
      stimulating hormone) had lower affinity. In second-messenger studies, the cyclic
      MSH analogues MTII and SHU9119 acted as potent agonist and antagonist
      respectively at the rainbow trout MC4 receptor, indicating that these ligands are
      suitable for physiological studies in rainbow trout. Interestingly, we found that
      the rainbow trout MC4 receptor has a natural high-affinity binding site for zinc
      ions (0.5 microM) indicating that zinc may play an evolutionary conserved role at
      this receptor. Reverse transcription PCR indicates that the rainbow trout
      receptors are expressed both in peripheral tissues and in the central nervous
      system, including the telencephalon, optic tectum and hypothalamus. Overall, this
      analysis indicates that the rainbow trout MC4 and MC5 receptors have more in
      common than their mammalian counterparts, which may suggest that these two
      receptors have a closer evolutionary relationship than the other MC receptor
      subtypes.

PMID- 14965342
TI  - Catalytic reaction of cytokinin dehydrogenase: preference for quinones as
      electron acceptors.
AB  - The catalytic reaction of cytokinin oxidase/dehydrogenase (EC 1.5.99.12) was
      studied in detail using the recombinant flavoenzyme from maize. Determination of
      the redox potential of the covalently linked flavin cofactor revealed a
      relatively high potential dictating the type of electron acceptor that can be
      used by the enzyme. Using 2,6-dichlorophenol indophenol, 2,3-dimethoxy-5-methyl
      1,4-benzoquinone or 1,4-naphthoquinone as electron acceptor, turnover rates with
      N6-(2-isopentenyl)adenine of approx. 150 s(-1) could be obtained. This suggests
      that the natural electron acceptor of the enzyme is quite probably a p-quinone or
      similar compound. By using the stopped-flow technique, it was found that the
      enzyme is rapidly reduced by N6-(2-isopentenyl)adenine (k(red)=950 s(-1)). Re
      oxidation of the reduced enzyme by molecular oxygen is too slow to be of
      physiological relevance, confirming its classification as a dehydrogenase.
      Furthermore, it was established for the first time that the enzyme is capable of
      degrading aromatic cytokinins, although at low reaction rates. As a result, the
      enzyme displays a dual catalytic mode for oxidative degradation of cytokinins: a
      low-rate and low-substrate specificity reaction with oxygen as the electron
      acceptor, and high activity and strict specificity for isopentenyladenine and
      analogous cytokinins with some specific electron acceptors.

PMID- 14965344
TI  - YACOP: Enhanced gene prediction obtained by a combination of existing methods.
AB  - The performance of gene-predicting tools varies considerably if evaluated with
      respect to the parameters sensitivity and specificity or their capability to
      identify the correct start codon. We were interested to validate tools for gene
      prediction and to implement a metatool named YACOP, which combines existing tools
      and has a higher performance. YACOP parses and combines the output of the three
      gene-predicting systems Criticia, Glimmer and ZCURVE. It outperforms each of the
      programs tested with its high sensitivity and specificity values combined with a
      larger number of correctly predicted gene starts. Performance of YACOP and the
      gene-finding programs was tested by comparing their output with a carefully
      selected set of annotated genomes. We found that the problem of identifying genes
      in prokaryotic genomes by means of computational analysis was solved
      satisfactorily. In contrast, the correct localization of the start codon still
      appeared to be a problem, as in all cases under test at least 7.8% and up to
      32.3% of the positions given in the annotations differed from the locus predicted
      by any of the programs tested. YACOP can be downloaded from
      http://www.g2l.bio.uni-goettingen.de.

PMID- 14965343
TI  - Mast cell- and dendritic cell-derived exosomes display a specific lipid
      composition and an unusual membrane organization.
AB  - Exosomes are small vesicles secreted from multivesicular bodies, which are able
      to stimulate the immune system leading to tumour cell eradication. We have
      analysed lipids of exosomes secreted either upon stimulation from rat mast cells
      (RBL-2H3 cells), or constitutively from human dendritic cells. As compared with
      parent cells, exosomes displayed an enrichment in sphingomyelin, but not in
      cholesterol. Phosphatidylcholine content was decreased, but an enrichment was
      noted in disaturated molecular species as in phosphatidylethanolamines.
      Lyso(bis)phosphatidic acid was not enriched in exosomes as compared with cells.
      Fluorescence anisotropy demonstrated an increase in exosome-membrane rigidity
      from pH 5 to 7, suggesting their membrane reorganization between the acidic
      multivesicular body compartment and the neutral outer cell medium. NMR analysis
      established a bilayer organization of exosome membrane, and ESR studies using 16
      doxyl stearic acid demonstrated a higher flip-flop of lipids between the two
      leaflets as compared with plasma membrane. In addition, the exosome membrane
      exhibited no asymmetrical distribution of phosphatidylethanolamines. Therefore
      exosome membrane displays a similar content of the major phospholipids and
      cholesterol, and is organized as a lipid bilayer with a random distribution of
      phosphatidylethanolamines. In addition, we observed tight lipid packing at
      neutral pH and a rapid flip-flop between the two leaflets of exosome membranes.
      These parameters could be used as a hallmark of exosomes.

PMID- 14965345
TI  - Investigation of interaction between Pax-5 isoforms and thioredoxin using de novo
      modelling methods.
AB  - Pax-5 transcription factor plays a crucial role in B-cell development, activation
      and differentiation. In murine B-cells four different isoforms of Pax-5 have been
      identified, and their role in the regulation of the activity of the wild-type
      protein was revealed although still not fully understood. Using theoretical
      methods, we investigated the properties of one region of the Pax-5e and Pax-5d
      isoforms (named UDE domain) and we present a possible theoretical model for the
      interaction of this domain with thioredoxin that have been previously postulated
      based on the experimental results. Domain UDE (MW 4.8 kDa) is characterised by an
      extremely high ratio of positively charged residues (8) in comparisons to
      negatively charged amino acids (3), as well as unusually large concentrations of
      prolines (11.6%) and cysteines (4.7%). This is indicative of its role in protein
      protein interaction. The experimental 3D structure for either UDE domain or for
      any analogous sequence is not yet available, and therefore we resorted to various
      bioinformatics methods in order to predict the secondary and 3D structure from
      the primary sequence of UDE. Physicochemical properties of the predicted UDE
      structure gave more indication about possibilities for UDE-thioredoxin binding.
      In addition, UDE domain was shown to have both sequence and structure analogous
      to a segment of NAD-reducing hydrogenase HOXS a subunit which is believed to
      interact with thioredoxin. These studies showed that the UDE domain in Pax-5d and
      Pax-5e represents an ideal binding site for thioredoxin and we developed a model
      of UDE-TRX complex with two disulphide bridges. The active site of thioredoxin
      remained exposed after binding to UDE in this model and therefore binding of
      thioredoxin to Pax-5d could explain the unexpectedly high resistance of this
      isoform to oxidation. The complex between thioredoxin and Pax-5e can be a method
      for transportation of thioredoxin into the nucleus and also into the the vicinity
      of Pax-5a, explaining the observed activator role of Pax-5e.

PMID- 14965346
TI  - Seven clusters in genomic triplet distributions.
AB  - In several recent papers new gene-detection algorithms were proposed for
      detecting protein-coding regions without requiring a learning dataset of already
      known genes. The fact that unsupervised gene-detection is possible is closely
      connected to the existence of a cluster structure in oligomer frequency
      distributions. In this paper we study the cluster structure of several genomes in
      the space of their triplet frequencies, using a pure data exploration strategy.
      Several complete genomic sequences were analyzed, using the visualization of
      tables of triplet frequencies in a sliding window. The distribution of 64
      dimensional vectors of triplet frequencies displays a well-detectable cluster
      structure. The structure was found to consist of seven clusters, corresponding to
      protein-coding information in three possible phases in one of the two
      complementary strands and in the non-coding regions with high accuracy (higher
      than 90% on nucleotide level). Visualizing and understanding the structure allows
      to analyze effectively the performance of different gene-prediction tools. Since
      the method does not require extraction of ORFs, it can be applied even for
      unassembled genomes.

PMID- 14965348
TI  - Mitochondria and aging: a role for the permeability transition?
AB  - When mitochondria are subjected to oxidative stress and relatively high [Ca2+],
      they undergo a "permeability transition" in which the inner membrane becomes
      freely permeable to low-molecular-weight solutes. This phenomenon reflects
      reversible deformation of the adenine nucleotide translocase, the loss of its
      native gating properties and the stabilization of the deformed state by
      cyclophilin-D. The permeability transition may be a factor in cell dysfunction
      associated with aging. This can manifest in a number of ways ranging, in the most
      severe, from impaired energy transduction and compromised viability to more
      subtle influences on the propagation of Ca2+ signals. This article critically
      examines data relevant to this issue.

PMID- 14965349
TI  - Oxidative stress and mitochondrial function with aging--the effects of calorie
      restriction.
AB  - Accumulated oxidative stress resulting from a gradual shift in the redox status
      of tissues is now considered to be a key mechanism underlying the aging process.
      Calorie-restricted (CR) feeding, an experimental protocol to extend survival and
      delay aging in rodents, is recognized to slow the rate of accrual of age-related
      oxidative stress. This conclusion is based on the increase in tissues with age of
      the oxidation products of proteins, lipids and DNA. The functional consequence,
      however, of the accumulation of these non-specific oxidative markers is more
      difficult to determine. A shift in the redox status of tissues with age and
      calorie restriction feeding may have a greater impact on cell function through
      activation of redox sensitive transcription factors than through the accumulation
      of these non-specific oxidative markers. Activation of such transcription factors
      will stimulate signalling pathways that will lead to a change in the gene
      expression profile and cell functioning. Little research has been conducted in
      this area. It has been proposed that CR feeding slows the rate of accrual of
      oxidative damage because mitochondria in these animals have a lower rate of
      superoxide generation when compared with mitochondria from control animals. This
      proposal is based on in vitro observations using isolated mitochondria and
      clearly requires further confirmation in isolated cells or using an in vivo
      approach. The application of metabolic control analysis to identify in isolated
      mitochondria the mechanism underlying this response has suggested one possible
      explanation for the lower superoxide production rates observed.

PMID- 14965350
TI  - Mitochondria: are they the seat of senescence?
AB  - The frequently quoted figure for the fractional univalent reduction of oxygen to
      superoxide in mitochondria is certainly too high by at least one order of
      magnitude. This is so because the higher number (2%) was derived from
      mitochondria whose cytochrome c oxidase was blocked with cyanide. Nevertheless,
      even the more correct number (0.1%) means that the production of O(2)(-) and
      H(2)O(2) in mitochondria is large and apt to result in damage to macromolecules
      in spite of such defensive enzymes as superoxide dismutases and glutathione
      peroxidase. The data available for nematodes and flies provide a compelling case
      for the view that the accumulation of oxidative damage to specific mitochondrial
      proteins leads to the progressive dysfunction that we see as senescence. The data
      available from work with mammals are much weaker and do not yet allow a strong
      position to be taken.

PMID- 14965351
TI  - Mitochondria, reactive oxygen species and longevity: some lessons from the Barja
      group.
AB  - To demonstrate that an uncoupling of respiration and phosphorylation, measured in
      vitro, reflects an in vivo situation, we badly need in vivo measurements of some
      uncoupling-linked parameters. The importance of this assertion is illustrated by
      studies of Barja and co-workers. A lower rate of H(2)O(2) production by
      mitochondria isolated from long-lived birds compared with short-lived mammals of
      the same body weight (see publications by Barja's and Sohal's groups) could be
      explained by (i) an in vivo difference or (ii) an in vitro artefact. In both
      cases, the reason for lower H(2)O(2) production may well be the same, i.e. a mild
      uncoupling of respiration in avian mitochondria showing lowered respiratory
      control. Again, this should be due to an in vivo operation of some bird-specific
      natural uncouplers (the first case) or stronger in vitro damage to the avian
      mitochondria during their isolation and incubation (the second). The latter
      possibility seemed more probable when Barja and co-workers revealed that the
      level of antioxidants in birds is lower than in mammals. However, further studies
      by the same group showed that the degree of unsaturation of fatty acids in birds
      is lower than in mammals, indicating a greater resistance of avian mitochondria
      to oxidative damage in vitro. Indeed, it was found that lipid peroxidation in
      isolated avian mitochondria occurs at a much lower rate than in mammals. More
      importantly, the in vivo level of peroxidation of lipids and proteins appears to
      be lower in birds than in mammals. Thus, it seems probable that longer lifespan
      of birds really does correlate with a slower rate of production of H2O2 by
      mitochondria in vivo.

PMID- 14965352
TI  - Is defective electron transport at the hub of aging?
AB  - The bulwark of the mitochondrial theory of aging is that a defective respiratory
      chain initiates the death cascade. The increased production of superoxide is
      suggested to result in progressive oxidant damage to cellular components and
      particularly to mtDNA that encodes subunits assembled in respiratory complexes.
      Earlier studies of respiration in muscle mitochondria obtained from large cohorts
      of patients supported this notion by showing that either singly or in
      combinations, the respiratory complexes exhibited decreased activity in the
      elderly. The following critique of the most cited publications over the past
      decade points out the systematic errors that put earlier work at odds with recent
      findings. These later investigations indicate that aging has no overt effect on
      either the electron transport system or oxidative phosphorylation.

PMID- 14965353
TI  - Mitochondrial influence on aging rate in Caenorhabditis elegans.
AB  - Virtually every model of mitochondrial involvement in aging shares the underlying
      proposition that mitochondrial dysfunction will accelerate the rate of aging.
      Caenorhabditis elegans is a post-mitotic organism with limited capacity for
      replacement and repair, and there is a great deal of evidence that interventions
      which decrease the induction of damage extend lifespan in this model. However,
      decreased availability of ubiquinone in adulthood has also been found to promote
      longevity and stress resistance, and evidence tentatively supports decreased
      mitochondrial function under these conditions. In addition, gene silencing
      experiments and mutations that target mitochondrial electron transport have also
      been found to increase lifespan and stress resistance in C. elegans, as has
      treatment with the mitochondrial inhibitor antimycin A. The involvement of damage
      by reactive oxygen species has been suggested, and yet many of these
      manipulations would be expected to increase the production of reactive oxygen
      species. The extension of lifespan by these interventions seems paradoxical and
      the mechanism, when it is elucidated, promises to have far-reaching significance.

PMID- 14965354
TI  - Mitochondrial membrane potential and aging.
AB  - The mitochondrial membrane potential (or protonmotive force) is the central
      bioenergetic parameter that controls respiratory rate, ATP synthesis and the
      generation of reactive oxygen species, and is itself controlled by electron
      transport and proton leaks. As a consequence of extensive research, there has
      emerged a consensus as to how these parameters integrate. Despite this consensus,
      the literature contains contradictory reports on the extent to which these
      parameters are modified in animal models of aging. This article critically
      examines the basis for a number of these reports.

PMID- 14965355
TI  - Oxidative damage in cultured human olfactory neurons from Alzheimer's disease
      patients.
AB  - Oxidative abnormalities precede clinical and pathological manifestations of
      Alzheimer's disease and are the earliest pathological changes reported in the
      disease. The olfactory pathways and mucosa also display the pathological features
      associated with Alzheimer's disease in the brain. Olfactory neurons are unique
      because they can undergo neurogenesis and are able to be readily maintained in
      cell culture. In this study, we examined neuronal cell cultures derived from
      olfactory mucosa of Alzheimer's disease and control patients for oxidative stress
      responses. Levels of lipid peroxidation (hydroxynonenal), N(epsilon)
      (carboxymethyl)lysine (glycoxidative and lipid peroxidation), and oxidative
      stress response (heme oxygenase-1) were measured immunocytochemically. We found
      increased levels for all the oxidative stress markers examined in Alzheimer's
      disease neurons as compared to controls. Interestingly, in one case of
      Alzheimer's disease, we found hydroxynonenal adducts accumulated in cytoplasmic
      lysosome-like structures in about 20% of neurons cultured, but not in neurons
      from control patients. These lysosome-like structures are found in about 100% of
      the vulnerable neurons in brains of cases of Alzheimer's disease. This study
      suggests that manifestations of oxidative imbalance in Alzheimer's disease extend
      to cultured olfactory neurons. Primary culture of human olfactory neurons will be
      useful in understanding the mechanism of oxidative damage in Alzheimer's disease
      and can even be utilized in developing therapeutic strategies.

PMID- 14965356
TI  - A primary pancreatic carcinoid tumour with unusual clinical complaints: A case
      report.
AB  - BACKGROUND: Unless metastatic or compressing the pancreatic duct, carcinoid of
      the pancreas are asymptomatic showing normal levels of serotonine and its
      metabolites in plasma and urine, thus resulting in delayed diagnosis and a
      consequent poor prognosis. However, if resection is timely accomplished, no local
      recurrence might be encountered and a normal survival might be expected in the
      absence of metastatic disease. CASE PRESENTATION: The reported case of pancreatic
      carcinoid tumour in a 62-year-old woman reporting only atypical symptoms
      consisting of intermittent epigastric pain and nausea. Urinary 5
      hydroxyindolacetic acid levels were within normal limits and only a slight
      elevation of serum serotonine level was detected on admission. After tumour
      localisation with endoscopic ultrasonography, left splenopancreasectomy with
      splenic, celiac and hepatic lymphadenectomy was carried out. CONCLUSION: The role
      of endoscopic ultrasonography in early detection and precise localisation of
      pancreatic carcinoids, as well as the role of somatostatin-receptor scintigraphy
      with 111Indium labelled pentreotide in excluding distant metastases, are
      confirmed. The radical resection with lymphadenectomy is recommended in order to
      have a precise histological examination and detect occult lymph node metastases.

PMID- 14965357
TI  - Gender difference in QTc prolongation of people with mental disorders.
AB  - BACKGROUND: We examined gender difference in QTc interval distribution and its
      related factors in people with mental disorders. METHODS: We retrospectively
      reviewed medical charts of patients discharged from a university psychiatric unit
      between November 1997 and December 2000. Subjects were 328 patients (145 males
      and 183 females) taking psychotropics at their admission. We examined patient
      characteristics, medical history, diagnosis, and medication before admission.
      RESULTS: Mean QTc interval was 0.408 (SD = 0.036). QTc intervals in females were
      significantly longer than those in males. QTc of females without comorbidity was
      significantly longer than that of males. CONCLUSION: The influence of gender
      difference on QTc prolongation in people with mental disorders merits further
      research.

PMID- 14965358
TI  - Antitumor activity of sugar-modified cytosine nucleosides.
AB  - Nucleoside analogues which show antimetabolic activity in cells have been
      successfully used in the treatment of various tumors. Nucleosides such as 1-beta
      D-arabinofuranosylcytosine (araC), 6-mercaptopurine, fludarabine and cladribine
      play an important role in the treatment of leukemias, while gemcitabine, 5
      fluorouracil and its prodrugs are used extensively in the treatment of many types
      of solid tumors. All of these compounds are metabolized similarly to endogenous
      nucleosides and nucleotides. Active metabolites interfere with the de novo
      synthesis of nucleosides and nucleotides or inhibit the DNA chain elongation
      after being incorporated into the DNA strand as terminators. Furthermore,
      nucleoside antimetabolites incorporated into the DNA strand induce strand-breaks
      and finally cause apoptosis. Nucleoside antimetabolites target one or more
      specific enzyme(s). The mode of inhibitory action on the target enzyme is not
      always similar even among nucleoside antimetabolites which have the same
      nucleoside base, such as araC and gemcitabine. Although both nucleosides are
      phosphorylated by deoxycytidine kinase and are also good substrates of cytidine
      deaminase, only gemcitabine shows antitumor activity against solid tumors. This
      suggests that differences in the pharmacological activity of these nucleoside
      antimetabolites may reflect different modes of action on target molecules. The
      design, in vitro cytotoxicity, in vivo antitumor activity, metabolism and
      mechanism of action of sugar-modified cytosine nucleosides, such as (2'S)-2'
      deoxy-2'-C-methylcytidine (SMDC), 1-(2-deoxy-2-methylene-beta-D-erythro
      pentofuranosyl)cytosine (DMDC), 1-(2-C-cyano-2-deoxy-1-beta-D-arabino
      pentofuranosyl)cytosine (CNDAC) and 1-(3-C-ethynyl-beta-D-ribo-pentofura
      nosyl)cytosine (ECyd), developed by our groups, are discussed here.

PMID- 14965359
TI  - DNA repair and cancer: lessons from mutant mouse models.
AB  - DNA damage, if the repair process, especially nucleotide excision repair (NER),
      is compromised or the lesion is repaired by some other error-prone mechanism,
      causes mutation and ultimately contributes to neoplastic transformation.
      Impairment of components of the DNA damage response pathway (e.g., p53) is also
      implicated in carcinogenesis. We currently have considerable knowledge of the
      role of DNA repair genes as tumor suppressors, both clinically and
      experimentally. The deleterious clinical consequences of inherited defects in DNA
      repair system are apparent from several human cancer predisposition syndromes
      (e.g., NER-compromised xeroderma pigmentosum [XP] and p53-deficient Li-Fraumeni
      syndrome). However, experimental studies to support the clinical evidence are
      hampered by the lack of powerful animal models. Here, we review in vivo
      experimental data suggesting the protective function of DNA repair machinery in
      chemical carcinogenesis. We specifically focus on the three DNA repair genes,
      O(6)-methylguanine-DNA methyltransferase gene (MGMT ), XP group A gene (XPA) and
      p53. First, mice overexpressing MGMT display substantial resistance to
      nitrosamine-induced hepatocarcinogenesis. In addition, a reduction of spontaneous
      liver tumors and longer survival times were evident. However, there are no known
      mutations in the human MGMT and therefore no associated cancer syndrome.
      Secondly, XPA mutant mice are indeed prone to spontaneous and carcinogen-induced
      tumorigenesis in internal organs (which are not exposed to sunlight). The
      concomitant loss of p53 resulted in accelerated onset of carcinogenesis. Finally,
      p53 null mice are predisposed to brain tumors upon transplacental exposure to a
      carcinogen. Accumulated evidence in these three mutant mouse models firmly
      supports the notion that the DNA repair system is vital for protection against
      cancer.

PMID- 14965360
TI  - Detection of a smaller, 32-kDa 8-oxoguanine DNA glycosylase 1 in 3'-methyl-4
      dimethylamino-azobenzene-treated mouse liver.
AB  - We previously reported that 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB)
      increased the 8-hydroxyguanine (8-OH-Gua) content in nuclear DNA and the base
      excision repair activity in mouse liver. However, to understand the mechanism of
      3'-MeDAB carcinogenesis, a further investigation of the 8-OH-Gua repair systems
      was necessary. In this report, we examined the expression of the repair enzyme, 8
      oxoguanine DNA glycosylase 1 (OGG1), in 3'-MeDAB-treated mouse liver. We prepared
      four kinds of anti-peptide polyclonal antibodies raised against mouse OGG1
      (mOGG1). The sequences used as epitopes were designed from positions located
      close to the N-terminus, the nuclear localization signal (NLS), and the regions
      containing Lys(249) and Asp(267), which are involved in the catalytic mechanisms
      of mOGG1 (glycosylase and lyase, respectively). Immunoblotting, using all four
      antibodies, revealed a 32-kDa protein (mOGG1-32) in addition to the 38-kDa mOGG1
      in the 3'-MeDAB-treated mouse liver. Moreover, immunostaining with mOGG1 antibody
      yielded strong, positive signals in the 3'-MeDAB-treated mouse liver nuclei.
      However, we could not detect any difference in the Ogg1 mRNA expression pattern.
      Although the function of mOGG1-32 remains unclear, these findings suggest that 3'
      MeDAB may alter the function of the DNA repair protein, and this action may be
      related to 3'-MeDAB carcinogenesis.

PMID- 14965361
TI  - Rapid analysis of gene expression changes caused by liver carcinogens and
      chemopreventive agents using a newly developed three-dimensional microarray
      system.
AB  - We investigated changes of gene expression in livers of rats treated with
      carcinogens and tumor promoters using a novel three-dimensional microarray system
      developed by Olympus Optical Co., Ltd., to assess the feasibility of predicting
      modifying effects on hepatocarcinogenesis on the basis of changes in the
      patterns. For this purpose, two genotoxic carcinogens, two nongenotoxic
      carcinogens (promoters) and seven candidate chemopreventive agents were examined.
      Six-week-old male F344 rats were treated for 2 weeks with the 11 chemicals (0.05%
      phenobarbital, 0.3% clofibrate, 0.01% N-diethylnitrosamine (DEN), 0.01% 2-amino
      3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 1% catechol, 1% caffeic acid,
      0.05% nobiletin, 0.05% garcinol, 0.05% auraptene, 0.05% zermbone and 0.05% 1'
      acetoxychavicol acetate (ACA). Test chemicals were mixed in food with the
      exception of DEN, which was administered in drinking water. RNAs from liver were
      then analyzed using two kinds of customized microarrays (PamChip(?xa8) microarray
      A spotted for 28 genes of drug-metabolizing enzymes in duplicate, and PamChip
      microarray B spotted for 131 genes which are known to be up- or down-regulated in
      hepatocarcinoma cells). Hybridization and subsequent analysis were usually
      completed within 2 h and the data obtained were highly reproducible. Carcinogens
      were classified into genotoxic and nongenotoxic substances by clustering
      analysis. We could also divide test chemicals into carcinogens and
      chemopreventive agents from their effects on gene expression. In this study, we
      have thus shown that it is feasible to predict the modifying effects of chemicals
      on the basis of changes of gene expression patterns after only 2 weeks of
      exposure, using our novel three-dimensional microarrays.

PMID- 14965362
TI  - Cloning of a G-protein-coupled receptor that shows an activity to transform
      NIH3T3 cells and is expressed in gastric cancer cells.
AB  - The present study was directed towards the identification of novel factors
      involved in the transformation process leading to the formation of gastric
      cancer. A cDNA library from human gastric cancer cells was constructed using a
      retroviral vector. Functional cloning was performed by screening for
      transformation activity in transduced NIH3T3 cells. Six cDNA clones were
      isolated, including one encoding the elongation factor 1alpha subunit, which was
      already known to play a role in tumorigenesis. One cDNA (clone 56.2), which was
      repeatedly isolated during the course of screening, encoded a protein identical
      to a G-protein-coupled receptor protein, GPR35. In addition, another cDNA clone
      (72.3) was found to be an alternatively spliced product of the GPR35 gene,
      whereby 31 amino acids were added to the N-terminus of GPR35. Hence, the proteins
      encoded by clones 56.2 and 72.3 were designated GPR35a and GPR35b, respectively.
      RT-PCR experiments revealed that GPR35 gene expression is low or absent in
      surrounding non-cancerous regions, while both mRNAs were present in all of the
      gastric cancers examined. The level of 72.3-encoded mRNA was consistently
      significantly higher than that of 56.2 encoded mRNA. An expression pattern
      similar to that observed in gastric cancers was detected in normal intestinal
      mucosa. Based on the apparent transformation activities of the two GPR35 clones
      in NIH3T3 cells, and the marked up-regulation of their expression levels in
      cancer tissues, it is speculated that these two novel isoforms of GPR35 are
      involved in the course of gastric cancer formation.

PMID- 14965363
TI  - Correlation of EPHA2 overexpression with high microvessel count in human primary
      colorectal cancer.
AB  - Evidence suggests that the erythropoietin-producing hepatocellular (EPH) receptor
      tyrosine kinases (RTKs) and their ephrin (EFN) ligands are involved in human
      carcinogenesis. Expression of two of them, EFNA1 ligand and its receptor, EPHA2,
      has been proposed to contribute to tumor-induced neovascularization. Colorectal
      cancers were examined for expressions of EPHA2 and its ligand EFNA1 by semi
      quantitative RT-PCR, and double-immunostained for EPHA2 and CD34. Microvessels in
      the tumors were counted. Double-staining was also performed in 25 cases of
      adenoma with focal cancer for comparison. Trends of overexpression of both EPHA2
      and EFNA1 was found in tumor tissue compared to the corresponding normal tissue
      in the same specimen [22/37 (59.5%) and 25/37 (67.5%), respectively; P = 0.100
      for EPHA2 and P = 0.009 for EFNA1]. Overexpression of EPHA2 and EFNA1 was noted
      more frequently in the early stage than in the late stage [EPHA2, 15/21 (71.4%)
      vs. 7/16 (43.8%), P = 0.007; EFNA1, 15/21 (71.4%) vs. 10/16 (62.5%), P = 0.007].
      Both EPHA2 and EFNA1 were more frequently overexpressed in smaller tumors (less
      than 5 cm) than in larger tumors [EPHA2, 15/21 (71.4%) vs. 7/16 (43.8%), P =
      0.017; EFNA1, 16/21 (76.2%) vs. 8/16 (50%), P = 0.001]. Tumors less than 5 cm in
      diameter and in stages I and II were significantly more likely to overexpress
      EPHA2 and EFNA1 (P = 0.001 for EPHA2, P = 0.001 for EFNA1). Microvessel counts
      (MVCs) after immunostaining for CD34 were significantly correlated (r = 0.343, P
      = 0.037) with overexpression of EPHA2. EPHA2-expressing focal cancer also
      surrounded microvessels in adenomas with focal cancers. These findings suggest an
      involvement of EPHA2 in colon carcinogenesis, mainly in stages I and II, and
      probably through their effect on microvessel induction.

PMID- 14965364
TI  - Increased expression of integrin alpha3beta1 in highly brain metastatic subclone
      of a human non-small cell lung cancer cell line.
AB  - To clarify the roles of integrin and extracellular matrix (ECM) in the process of
      non-small cell lung cancer (NSCLC) brain metastasis, we established an in vivo
      model of brain metastasis of human NSCLC cell line EBC-1/original in athymic
      mice, and established highly brain metastatic subclone EBC-1/brain and highly
      bone metastatic subclone EBC-1/bone. Integrin expression of these subclones was
      evaluated by flow cytometry. In vitro cell attachment, migration and
      proliferation assays with ECMs were performed using these subclones. Expression
      of integrin alpha3 subunit was higher in EBC-1/brain than in both EBC-1/original
      and EBC-1/bone. In vitro cell attachment, migration, and proliferation assays
      revealed that EBC-1/brain had higher affinity and higher reactivity to laminin
      than EBC-1/original and EBC-1/bone. Blocking of integrin alpha3beta1
      significantly (P < 0.05) decreased brain metastasis by EBC-1/brain. Interaction
      of integrin alpha3beta1 and laminin plays important roles in the process of brain
      metastasis of non-small cell lung cancer.

PMID- 14965365
TI  - Mutation of the von Hippel-Lindau (VHL) gene in human colorectal carcinoma:
      association with cytoplasmic accumulation of hypoxia-inducible factor (HIF)
      1alpha.
AB  - We screened for mutations in the von Hippel-Lindau (VHL) tumor suppressor gene
      and examined the relationship of these mutations with expression of hypoxia
      inducible factor (HIF)-1alpha protein in human colorectal carcinomas. DNAs were
      extracted from 130 paraffin-embedded tumor specimens and subjected to polymerase
      chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis
      followed by direct sequencing. We identified 13 mutations in the coding sequence
      of VHL, 12 of which were unique events. Three mutations were located in exon 2
      and the others in exon 3. These mutations were detected in 10 of 88 (11.4%)
      tumors tested. Furthermore, seven of the 13 (53.8%) VHL mutants
      immunohistochemically showed high HIF-1alpha expression. The mean percentage of
      cells with strong cytoplasmic HIF-1alpha expression was 67.5% in tumors with VHL
      mutations, and this level was significantly higher than that in tumors without
      mutations (50.8%, P < 0.05). These findings suggest that mutations in VHL may
      play a role in colorectal carcinoma via activation of the HIF-related
      transcriptional cascade.

PMID- 14965366
TI  - Inhibition of RL male 1 tumor growth in BALB/c mice by introduction of the RLakt
      gene coding for antigen recognized by cytotoxic T-lymphocytes and the GM-CSF gene
      by in vivo electroporation.
AB  - A DNA vaccine for inducing a tumor immune response was investigated using a well
      characterized murine model tumor antigen. We demonstrated that in vivo
      electroporation augmented the induction of IFNgamma enzyme-linked immunospot
      (ELISPOT) and cytotoxic T lymphocyte (CTL) generation against pRL1a peptide in
      BALB/c spleen cells upon immunization with RLakt plasmid. Immunization without in
      vivo electroporation resulted in only a marginal induction of IFNgamma ELISPOT
      and CTL generation. Furthermore, co-injection of GM-CSF and RLakt plasmids
      significantly enhanced the induction of IFNgamma ELISPOT and CTL generation
      compared to the injection of RLakt plasmid alone. Inhibition of RL male 1 tumor
      growth was observed by injecting BALB/c mice with GM-CSF and RLakt plasmids using
      in vivo electroporation, although no effect was observed against an established
      tumor using the same treatment. No growth inhibition was observed without in vivo
      electroporation. Immunization with either RLakt plasmid alone, or GM-CSF and
      pCIneo control plasmids using in vivo electroporation did not inhibit RL male 1
      tumor growth.

PMID- 14965367
TI  - Potent antitumor effect elicited by superantigen-linked tumor cells transduced
      with heat shock protein 70 gene.
AB  - Heat shock proteins (HSP) induce antitumor-specific immunity via a unique
      mechanism, but HSP alone fails to produce a satisfactory antitumor efficacy. We
      considered that the potent immune-activation of superantigen (SAg) might assist
      HSP to elicit a strong tumor-antigen-specific immunity. We initially prepared B16
      melanoma cells linked to SAg SEA via a fusion protein with a transmembrane
      sequence (TM), and demonstrated that SEA thus anchored on the tumor cell surface
      could elicit strong antitumor immunity. We then prepared cells transduced with an
      inducible heat shock protein 70 (HSP70) gene, and bearing SEA-TM fusion protein
      on the cell surface, and used these cells as a dual-modified vaccine. In this
      study, either in a therapeutic setting or in a pre-immune model, the SEA-anchored
      vaccine or the HSP70 gene-modified vaccine induced marked tumor suppression,
      prolonged survival, augmented lymphocyte proliferation and higher NK and CTL
      activity in C57BL/6 mice compared with their controls (P < 0.01), though they
      were less effective than the dual-modified vaccine. Among these vaccines, the
      dual-modified vaccine showed the best therapeutic efficacy in B16 melanoma
      bearing mice and gave the greatest protection against wild-type B16 melanoma
      challenge. The results indicated that the dual-modified vaccine could induce a
      potent tumor-antigen-specific immune response in addition to an increase of non
      specific immunity. This study offers a novel approach to bridging specific and
      non-specific immunity for cancer therapy.

PMID- 14965368
TI  - DE-310, a novel macromolecular carrier system for the camptothecin analog DX
      8951f: potent antitumor activities in various murine tumor models.
AB  - DE-310 is a novel macromolecular conjugate composed of DX-8951f, a camptothecin
      analog, and a carboxymethyldextran polyalcohol carrier, which are covalently
      linked via a peptidyl spacer. In a murine Meth A (fibrosarcoma) solid tumor
      model, once daily x 5 treatments (qd x 5) with DX-8951f at the maximum tolerated
      dose (MTD) were required to shrink the tumor, and DX-8951f (qd x 5) at 1/4 MTD
      was required to inhibit tumor growth. A single treatment (qd x 1) with DE-310 at
      the MTD or 1/4 MTD shrank the tumor, with no body weight loss occurring at 1/4
      MTD. Even at 1/16 MTD, DE-310 inhibited tumor growth. In a long-term assay, Meth
      A solid tumors disappeared in mice treated with DE-310 (qd x 1) at the MTD and
      1/2 MTD, and all 6 mice remained tumor-free on the 60th day after administration.
      Repeated injection (4 times) on schedules of every 3 days, 7 days or 14 days
      demonstrated that multiple treatment with DE-310 produced greater tumor growth
      delay than a single treatment with DE-310. Against 5 human tumor (colon and lung
      cancer) xenografts in mice, DE-310 (qd x 1) was as effective as DX-8951f
      administered once every 4 days, 4 times. The life-prolonging activity of DE-310
      was assessed in lung (3LL, Lewis lung carcinoma) and liver (M5076, histiocytoma)
      metastasis models. Against 3LL, DE-310 (qd x 1) at the MTD to 1/3 MTD
      significantly prolonged survival, with an increase in life span (ILS) of 4.8- to
      1.6-fold, respectively, over that in untreated control mice. Also, DE-310 (qd x
      1) significantly prolonged survival in the liver metastasis model of M5076. These
      results demonstrate that DE-310 is a promising agent for the treatment of cancer.

PMID- 14965369
TI  - Proteasome inhibitor PS-341 induces growth arrest and apoptosis of non-small cell
      lung cancer cells via the JNK/c-Jun/AP-1 signaling.
AB  - Proteasome inhibitor PS-341 induces growth arrest and apoptosis of multiple
      myeloma (MM) cells via inactivation of NF-kappaB in vitro and has afforded some
      objective responses in individuals with relapsed, refractory MM. However, the
      activity of PS-341 against non-hematological malignancies remains to be fully
      elucidated. In this study, we found that PS-341 induced growth arrest and
      apoptosis of NCI-H520 and -H460 non-small cell lung cancer (NSCLC) cells in
      conjunction with markedly up-regulated levels of p21(waf1) and p53, and down
      regulation of bcl-2 protein in these cells. Also, PS-341 caused phosphorylation
      of c-Jun NH(2)-terminal kinase (JNK) and c-Jun, and enhanced AP-1/DNA binding
      activities in these cells as measured by western blotting and enzyme-linked
      immunosorbent assay (ELISA), respectively. Interestingly, when the JNK/c-Jun/AP-1
      signal pathway was disrupted by the JNK inhibitor SP600125, the ability of PS-341
      to inhibit the growth of NSCLC cells and to up-regulate the levels of p21(waf1)
      in these cells was blunted, but the expression of p53 was sustained at a high
      level, suggesting that the JNK/c-Jun/AP-1 signal pathway might mediate the anti
      lung cancer effects of PS-341, with p21(waf1) playing the central role. Thus, PS
      341 might be useful for the treatment of individuals with NSCLC.

PMID- 14965370
TI  - Ultrasound-induced killing of monocytic U937 cells enhanced by 2,2'-azobis(2
      amidinopropane) dihydrochloride.
AB  - To determine the effect of 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)
      on ultrasound (US)-induced cell killing, human monocytic leukemia cells (U937)
      were incubated at various temperatures (25.0, 37.0 and 40.0 degrees C) for 1 min
      in air-saturated phosphate-buffered solution (PBS) containing 50 mM AAPH before
      exposure to nonthermal 1 MHz US for 1 min at an intensity of 2.0 W/cm(2). Cell
      viability was determined by means of the Trypan blue dye exclusion test
      immediately after sonication. Apoptosis was measured after 6-h incubation post
      sonication by flow cytometry. Free radicals generated by AAPH, a temperature
      dependent free radical generator, or US or both were also investigated using
      electron paramagnetic resonance (EPR) spin trapping. The results showed that US
      induced cell lysis and apoptosis were enhanced in the presence of AAPH regardless
      of the temperature at the time of sonication. At 40.0 degrees C, US alone induced
      increased cell killing, while AAPH alone is capable of inducing significant but
      minimal apoptosis at this temperature. Although free radicals were increased in
      the combined treatment, this increase did not correlate well with cell killing.
      The mechanism of enhancement points to the increased uptake of the agent during
      sonication rather than potentiation by AAPH. These findings suggest the clinical
      potential of temperature-dependent free radical generators in cancer therapy with
      therapeutic US.

PMID- 14965371
TI  - p53-independent anti-tumor effects of the nitrogen-containing bisphosphonate
      zoledronic acid.
AB  - Zoledronic acid (ZOL), a nitrogen-containing bisphosphonate, exerts anti-tumor
      effects by inhibiting the prenylation of small GTPases. We have also reported
      that ZOL shows an anti-leukemic effect by inducing apoptosis throughout the S
      phase to the G(2) / M boundary. Here, we studied the effects of ZOL on various
      cell cycle regulators, including p53, cyclin-dependent kinases (CDKs), CDK
      inhibitors and cyclins, using BV173 leukemia and HCT116 colorectal carcinoma cell
      lines, harboring wild-type (wt-) p53. ZOL induced the accumulation of neither p53
      nor p21(WAF1/CIP1) during the execution of apoptosis in BV173 cells. Therefore,
      we investigated the dependence of ZOL-induced apoptosis on intact p53 by using wt
      p53 HCT116 and a p53-degraded HCT116 subline, and observed no significant
      difference. p57(KIP2) was upregulated by ZOL in BV173 cells, but not in HCT116
      cells. Flow cytometric analyses showed that ZOL also impaired the cell cycle
      dependent expression patterns of cyclins A, B and D3 in BV173. In conclusion, the
      p53-independent anti-tumor activities of ZOL suggest that it may be an attractive
      agent for treating cancers, including those with chemoresistance resulting from
      the loss of p53 function. ZOL also affected the coordinate expression patterns of
      several cell cycle regulators during the execution of anti-tumor activity.

PMID- 14965372
TI  - New approaches to identification of biomarkers for early cancer detection: The
      Thirteenth International Symposium of the Hiroshima Cancer Seminar, October 2003.

PMID- 14965373
TI  - Transplantation of monocytes: a novel strategy for in vivo augmentation of
      collateral vessel growth.
AB  - Therapeutic augmentation of collateral vessel growth (arteriogenesis) is of
      particular clinical interest. Because monocytes localize to areas of collateral
      growth and create a highly arteriogenic environment through secretion of multiple
      growth factors, we tested the hypothesis that monocyte "homing" can
      therapeutically be exploited. We have used a rabbit model of arteriogenesis to
      investigate the therapeutic potential of transplanted rabbit monocytes that were
      either ex vivo stimulated or adenovirally transduced to express a transgene
      encoding an arteriogenic growth factor. The monocytes were intravenously injected
      24 hr or 7 days after ligation of the animal's right femoral artery. Seven days
      after transplantation collateral flow was determined with a doppler flow probe
      and collateral vessels were quantified angiographically. Whereas transplantation
      of allogeneic cells (same species) resulted in a strong promotion of
      arteriogenesis, most likely through induction of local inflammation and
      recruitment of recipient monocytes, transplantation of autologous cells (same
      animal) was not able to significantly augment collateralization. However, when
      autologous monocytes were used as vehicles to deliver granulocyte macrophage
      colony stimulating factor as therapeutic transgene, collateralization was
      strongly augmented. Their localization to the site of collateral development
      posttransplantation was demonstrated by ex vivo transduction with beta
      galactosidase. Because isolation of monocytes is clinically widely available
      their ex vivo engineering and transplantation represents an intriguing new
      strategy for therapeutic arteriogenesis.

PMID- 14965374
TI  - Low-level tyrosine hydroxylase (TH) expression allows for the generation of
      stable TH+ cell lines of human neural stem cells.
AB  - Genetic engineering of neurotransmitter metabolic routes is important for the
      development of neurotransmitter-producing cells for the ex vivo gene therapy of
      many CNS diseases. Human neural stem cells (hNSCs) are excellent candidates to
      serve this role, but, for the case of Parkinson's disease, the cells do not
      normally express the rate-limiting dopamine (DA) synthesis enzyme tyrosine
      hydroxylase (TH), and are not equipped with the detoxifying mechanisms needed to
      prevent the neurotoxicity associated with the DA phenotype. In this study we have
      examined the capacity of hNSCs for ectopic expression of human TH. High-level TH
      expression (from viral promoters) leads to growth arrest and hNSC death
      (associated with an increase in p53 expression and nuclear fragmentation), which
      can be counteracted by treatment with a pan-caspase inhibitor. As a consequence,
      stable TH-expressing hNSC sublines could not be derived using viral promoters. In
      contrast, moderate TH expression (from a human housekeeping promoter,
      polyubiquitin gene), allows for stable TH+ subclone derivation, seemingly
      originating from low-expressing cells. Our results are thus compatible with the
      view that stable TH-expressing hNSC lines can be generated if TH expression
      levels are kept at a moderate level, and that the goal normally set of aiming at
      high-level TH expression may need to be reconsidered. These results may be
      relevant for the generation of TH/DA-producing human neural cells for in vitro
      and neurotransplantation research in Parkinson's disease.

PMID- 14965375
TI  - CCL3/MIP-1alpha is a potent immunostimulator when coexpressed with interleukin-2
      or granulocyte-macrophage colony-stimulating factor in a leukemia/lymphoma
      vaccine.
AB  - Chemokines orchestrate trafficking of immune effector cells during inflammation.
      Here we demonstrate that chemokines also serve to potentiate effector cell
      mediated antineoplastic immune responses in vaccination strategies. As a critical
      mediator of inflammation, macrophage inflammatory protein 1alpha (CCL3/MIP
      1alpha) attracts and stimulates both antigen-presenting and cytotoxic cells. In
      the A20 leukemia/lymphoma vaccine model, we explored the efficacy of MIP-1alpha
      in combination with interleukin-2 (IL-2) or granulocyte-macrophage colony
      stimulating factor (GM-CSF). After subcutaneous injection of the MIP-1alpha + IL
      2 or MIP-1alpha + GM-CSF combination vaccine, focal but pronounced infiltrates of
      CD4+ and CD8+ T cells were observed at the vaccination sites. In mice with
      preestablished leukemia/lymphoma, survival is significantly improved in animals
      treated with MIP-1alpha + GM-CSF- and MIP-1alpha + IL-2-secreting vaccines.
      Protection is superior in the MIP-1alpha + GM-CSF group, with the effects of MIP
      1alpha and GM-CSF being synergistic. In contrast, suppression of lymphoblast
      proliferation by single-immunogen vaccines secreting MIP-1alpha, GM-CSF, or IL-2
      alone does not translate to improved survival. The systemic protective effects
      afforded by the MIP-1alpha + IL-2 or MIP-1alpha + GM-CSF combination are mediated
      by different effector cell populations. In the MIP-1alpha + IL-2 group,
      antineoplastic defense is mediated by CD8+ T and NK cells, whereas in the MIP
      1alpha + GM-CSF group CD4+ T cells are involved in addition to CD8+ cytotoxic T
      cells, underscoring that T cell help is critical for long-term protection. Thus
      combination of MIP-1alpha with different cytokines recruits different sets of
      effector cells into a potent antineoplastic immune response.

PMID- 14965376
TI  - Acute toxicity after high-dose systemic injection of helper-dependent adenoviral
      vectors into nonhuman primates.
AB  - Systemic intravascular delivery of adenoviral (Ad) vectors for liver-directed
      gene therapy has been widely employed because of its simplicity, noninvasiveness,
      and potential for high transduction. For first-generation Ad vectors (FGAd), this
      results in high but transient levels of transgene expression and long-term
      hepatotoxicity due to viral gene expression from the vector backbone.
      Furthermore, high doses also result in an acute innate inflammatory response with
      potentially lethal consequences. Unlike FGAd, helper-dependent Ad vectors (HDAd)
      contain no viral genes and can provide sustained, high-level transgene expression
      with negligible long-term toxicity. However, whether the absence of viral gene
      expression leads to any decrease of acute toxicity in nonhuman primates has yet
      to be determined. To address this, we injected one baboon with 5.6 x 10(12) HDAd
      viral particles (VP)/kg and a second with 1.1 x 10(13) VP/kg. Approximately 50%
      hepatocyte transduction, accompanied by mild and transient acute toxicity, was
      observed in the animal receiving the lower dose. In the animal receiving the
      higher dose, 100% hepatocyte transduction, accompanied by lethal acute toxicity,
      was observed. These results indicate that systemic delivery of HDAd, like FGAd,
      results in acute toxicity in baboons consistent with activation of the innate
      inflammatory response, the severity of which is dose dependent, and confirm the
      hypothesis that Ad-mediated acute toxicity is independent of viral gene
      expression.

PMID- 14965377
TI  - Transgene expression after rep-mediated site-specific integration into chromosome
      19.
AB  - We have used a plasmid-based transfection model of the adeno-associated virus
      (AAV) Rep-mediated site-specific integration (RMSSI) pathway to characterize the
      stability and expression of a site-specifically integrated transgene (either
      green fluorescent protein [GFP] or chloramphenicol acetyltransferase [CAT]).
      Three plasmids containing the AAV p5 integration efficiency element (p5IEE) have
      been used to study integration and transgene expression in HeLa cells: (1)
      pRepGFP(itr+) contains both AAV ITRs, rep, and p5IEE and can be used as either a
      plasmid or rAAV vehicle for integration; (2) pRepGFP(itr-) contains the AAV rep
      gene and the p5IEE; (3) pAd-p5CAT contains only the 138-bp p5IEE of AAV. The data
      presented demonstrate that in the absence of drug selection, all three constructs
      undergo site-specific integration (efficiencies of between 10 and 40% of
      transduced cell lines). At 6 weeks posttransfection most cell lines that
      underwent RMSSI also expressed the appropriate transgene product. By 18 weeks
      posttransfection cell lines that were established with rep in cis to the
      transgene showed a decline in transgene expression as well as a loss of transgene
      DNA. In many cell lines, there appears to be transgene-containing DNA that does
      not contribute to gene expression. Data support a model of gene expression and
      transgene instability through a Rep-mediated pathway. In contrast to rep
      containing cell lines, clonal cell lines containing p5IEECAT (with Rep provided
      in trans) maintained both the integrated transgene and transgene expression
      throughout the entire experimental time course (18 weeks).

PMID- 14965378
TI  - Characterization of CD20-transduced T lymphocytes as an alternative suicide gene
      therapy approach for the treatment of graft-versus-host disease.
AB  - We have previously proposed the CD20 molecule as a novel suicide gene for T
      lymphocytes in the context of allogeneic bone marrow transplantation, because
      CD20 can be used both as a selection marker and as a killer gene after exposure
      to the anti-CD20 therapeutic antibody rituximab. We now report on preclinical
      studies using this novel system, in which the best transduction protocol,
      reproducibility, yield, feasibility, and functionality of the transduced T
      lymphocytes have been investigated with a large donor series. Wild-type human
      CD20 cDNA was transduced into human T lymphocytes, using a Moloney-derived
      retroviral vector. Alternative protocols were tested by employing either one or
      four spinoculations (in which cells are centrifuged in the presence of retroviral
      vector supernatant) and stimulating T cells with phytohemagglutinin (PHA) or anti
      CD3/CD28. One spinoculation alone was sufficient to obtain approximately 30% CD20
      positive cells within four experimental days. Four spinoculations significantly
      increased transduction to 60%. A small difference in transduction efficiency was
      observed between the two stimulation methods, with PHA being superior to anti
      CD3/CD28. Transduced cells could be purified on immunoaffinity columns, with
      purity reaching 98% and yield being on average 50%. Finally, 86-97% of
      immunoselected T lymphocytes could be killed in vitro with rituximab and
      complement. More importantly, the CD20 transgene did not alter the functionality
      of T lymphocytes with respect to allogeneic recognition and cytotoxic response,
      anti-Epstein-Barr virus cytotoxic response, antigenic response to tetanus toxoid
      antigen, interleukin 2 (IL-2), IL-4, and interferon gamma production; chemotaxis
      in the presence of stromal cell-derived factor 1, phenotype for several
      activation markers including HLA-DR, CD25, CD69, and CD95, and T cell repertoire.

PMID- 14965379
TI  - Human gene therapy for malignant gliomas (glioblastoma multiforme and anaplastic
      astrocytoma) by in vivo transduction with human interferon beta gene using
      cationic liposomes.
AB  - Transfer of interferon beta gene via cationic liposomes has been found to induce
      regression of experimental glioma. We performed a pilot clinical trial of safety
      and effectiveness of this interferon beta gene therapy in five patients with
      malignant glioma (glioblastoma multiforme or anaplastic astrocytoma). Transgene
      expression and antitumor activity were detected in four patients. Two patients
      showed a partial response (>50% tumor reduction) and two others had stable
      disease 10 weeks after beginning therapy. One patient could not be evaluated
      because of previous treatment with gamma-knife therapy. This study suggests the
      feasibility and safety of interferon beta gene therapy, which may become an
      important treatment option for patients with malignant glioma.

PMID- 14965380
TI  - Transduction of long-term and mobilized peripheral blood-derived NOD/SCID
      repopulating cells by foamy virus vectors.
AB  - Foamy virus (FV) vectors are a promising gene delivery system for use in
      hematopoietic stem cell gene therapy. Previous FV vector marking studies in the
      NOD/SCID xenotransplantation model used umbilical cord blood (UCB)-derived SCID
      repopulating cells (SRCs) that were assayed 5-10 weeks posttransplantation. We
      now report efficient FV vector transduction (>65%) of UCB-derived primitive, long
      term SRCs engrafted for 18 weeks. In addition, we evaluated gene transfer into
      mobilized peripheral blood (MPB)-derived SRCs by improved, deleted FV vectors
      containing minimal cis-acting sequences and packaged by split helper constructs
      that would be appropriate for use in clinical trials. When used at a multiplicity
      of infection of 1 in a 10-hr transduction protocol, these improved vectors
      transduced 34% of engrafted MPB-derived SRCs.

PMID- 14965381
TI  - Phase I trial of intramuscular injection of a recombinant adeno-associated virus
      alpha 1-antitrypsin (rAAV2-CB-hAAT) gene vector to AAT-deficient adults.
AB  - A recombinant virus vector constructed from adeno-associated virus (AAV) that has
      been altered to carry the human alpha1-antitrypsin (hAAT) gene expressed from a
      hybrid chicken beta-actin promoter with a cytomegalovirus enhancer has been
      developed. The construct has been shown to initiate the production of hAAT in
      animal models closely matching the proposed human trial. The proposed clinical
      trial is an open-label, phase I study administering recombinant adeno-associated
      virus alpha1-antitrypsin (rAAV2-CB-hAAT) gene vector intramuscularly to AAT
      deficient human subjects where gene expression can be measured directly in blood
      samples to assess safety. Safety parameters will be measurement of changes in
      serum chemistries and hematology, urinalysis, pulmonary function testing, semen
      assay for vector genomes, immunologic response to AAT, and AAV, as well as
      reported subject history of any symptoms.

PMID- 14965383
TI  - Complementary medicine: implications for informed consent in general practice.

PMID- 14965384
TI  - Post-traumatic stress disorder: a challenge for primary care--misunderstood and
      incognito.

PMID- 14965385
TI  - Patient factors associated with duration of certified sickness absence and
      transition to long-term incapacity.
AB  - BACKGROUND: Despite a considerable increase in claims for long-term sickness
      benefits, and the impact of certifying sickness upon general practitioner (GP)
      workload, little is known about transition to long-term incapacity for work. AIM:
      To explore the relationship between patient factors and the transition from short
      term to long-term work incapacity, in particular focusing on mild mental health
      and musculoskeletal problems. SETTING: Nine practices comprising the Mersey
      Primary Care R&D Consortium. DESIGN: Prospective data collection and audit of
      sickness certificate details. METHOD: GPs issued carbonised sickness certificates
      for a period of 12 months. The resulting baseline dataset included claimant
      diagnosis, age, sex, postcode-derived deprivation score, and sickness episode
      duration. Associations of patient factors with sickness duration outcomes were
      tested. RESULTS: Mild mental disorder accounted for nearly 40% of certified
      sickness. Relatively few claimants had their diagnosis changed during a sickness
      episode. Risk factors for longer-term incapacity included increasing age, social
      deprivation, mild and severe mental disorder, neoplasm, and congenital illness.
      For mild mental disorder claimants, age, addiction, and deprivation were risk
      factors for relatively longer incapacity. For musculoskeletal problems, the
      development of chronic incapacity was significantly related to the nature of the
      problem. Back pain claimants were likely to return to work sooner than those with
      other musculoskeletal problems. CONCLUSIONS: In addition to the presenting
      diagnosis, a range of factors is associated with the development of chronic
      incapacity for work, including age and social deprivation. GPs should consider
      these when negotiating sickness certification with patients.

PMID- 14965386
TI  - What influences participants' treatment preference and can it influence outcome?
      Results from a primary care-based randomised trial for shoulder pain.
AB  - BACKGROUND: In randomised clinical trials (RCTs), outcome may be influenced by
      the opinions of the participants about the efficacy of treatments. AIM: To
      examine how initial treatment preferences of participants in a shoulder pain
      trial affected functional outcome and future treatment preferences. DESIGN OF
      STUDY: Observational cohort study nested within a multicentre, pragmatic RCT of
      steroid injection versus physiotherapy for unilateral shoulder pain. SETTING:
      Nine general practices in north Staffordshire. METHOD: Two hundred and seven
      adults were randomised in the trial. Disability scores and preferences of the
      participants for the trial treatments were elicited at two points: prior to
      randomisation and 6 months post-randomisation. A good functional outcome was
      defined as at least a halving in the disability score at the 6 months follow-up
      point. RESULTS: Pre-randomisation preferences were: 40% for injection and 20% for
      physiotherapy, and 40% gave no preference. A good outcome was achieved in a
      higher percentage of participants who gave a pre-randomisation treatment
      preference compared with those who did not (62% compared with 48% percentage
      difference = 14%; 95% confidence interval [CI] = -1 to 27%) with similar
      percentages in each preferred treatment group. However, receiving the preferred
      treatment did not confer any additional benefit in those who expressed a
      preference (receiving preferred treatment = 56%; not receiving preferred
      treatment = 69%). At 6 months post-randomisation, participants with a good, as
      opposed to poor, outcome were more likely to report as their preferred treatment
      the one to which they had been randomised, irrespective of pre-randomisation
      preference and whether the preferred treatment was received. CONCLUSION: This
      analysis suggests that preferences prior to treatment can affect outcome, but
      that treatment outcome is a stronger influence on post-treatment preferences. We
      present some empirical evidence to support the statement that treatment
      preferences can have important effects on the results of RCTs.

PMID- 14965387
TI  - Remedy or cure? Lay beliefs about over-the-counter medicines for coughs and
      colds.
AB  - BACKGROUND: Over 500 million is spent in the United Kingdom every year on over
      the-counter medicines for coughs and colds. Evidence for their pharmacological
      efficacy is lacking. AIM: To examine lay beliefs about over-the-counter medicines
      for coughs and colds. To explore whether the distinction between symptom relief
      and cure has the same relevance to lay people as it does to medical
      professionals. DESIGN OF STUDY: Small pilot study using qualitative techniques.
      SETTING: Variety sample of 11 patients attending the National Health Service walk
      in centre, Birmingham, England. METHOD: In-depth semi-structured interviews,
      including pile-sorting and fictional case histories, were used to explore
      participants' beliefs about the effects of over-the-counter medicines on coughs
      and colds. RESULTS: Eight of the 11 participants believed that at least one over
      the-counter cough medicine (most frequently Benylin for Chesty Coughs) could
      shorten, or "cure", an illness. Five participants thought that the majority of
      the medicines that they recognised would speed recovery rather than just relieve
      symptoms. CONCLUSIONS: There is a common confusion in the lay person's mind
      between the ability of a medicine to relieve symptoms, and its ability to cure a
      disease or to hasten recovery. This misunderstanding may affect the demand for
      primary care consultations.

PMID- 14965388
TI  - An evaluation of the impact of NICE guidance on GP prescribing.
AB  - BACKGROUND: One of the aims of the National Institute for Clinical Excellence
      (NICE) is to promote faster access to the best treatments. However, there is no
      published research on the impact that NICE guidance has had on prescribing
      decisions. AIMS: To explore the attitudes of general practitioners (GPs) to NICE
      guidance and to investigate any changes in prescribing patterns. DESIGN:
      Descriptive cross-sectional study. SETTING: North Devon Primary Care Trust.
      METHOD: Five technology appraisals most likely to impact on GP prescribing were
      investigated. Prescribing analysis and cost (PACT) data were analysed for changes
      in prescribing patterns before and after the publication of each technology
      appraisal. A postal questionnaire, developed from semi-structured interviews, was
      sent to all GPs within a single primary care trust (PCT) to explore factors that
      were encouraging or discouraging adherence to NICE guidance. RESULTS: PACT data
      showed that there was an increase in the prescribing of the drugs studied
      immediately after NICE guidance, with the exception of zanamivir (Relenza
      [GlaxoSmithKline]); only one zanamivir inhaler was prescribed during the study
      period. Although there was an increase in the prescribing of maintenance doses of
      proton pump inhibitors, there was also an increase in treatment doses. Eighty-one
      (82.7%) questionnaires were completed and returned. In general, there was a
      balance between the factors that encouraged and those that discouraged adherence.
      The main exception was zanamivir, where factors that discouraged adherence
      greatly exceeded factors that encouraged adherence. CONCLUSIONS: This study
      showed that NICE guidance in isolation had little impact on GP prescribing. Where
      the guidance coincided with information from other sources, or personal
      experience, there was some evidence that technology appraisals triggered an
      increase in prescribing, but that this was not always sustained. The
      recommendations of NICE concerning zanamivir were universally rejected and there
      was evidence that this had undermined confidence in NICE recommendations in
      general.

PMID- 14965389
TI  - Missed appointments in primary care: questionnaire and focus group study of
      health professionals.
AB  - BACKGROUND: The issue of missed appointments in primary care is important for
      patients and staff. Little is known about how missed appointments, and the people
      who miss them, are managed in primary care, or about effective strategies for
      managing missed appointments. AIMS: To understand the perceptions of primary care
      staff as to why patients miss appointments, to determine how these perceptions
      influence their management, and to explore the merit of different management
      strategies. DESIGN OF STUDY: A postal questionnaire survey and focus group
      interviews. SETTING: General practices in Yorkshire. RESULTS: Missed appointments
      were regarded as an important problem. Patient factors rather than practice
      factors were perceived as most important in causing missed appointments.
      Intervention strategies appeared to be driven by perceptions of why patients miss
      appointments. Negative attitudes, embodied in terms such as "offenders" to refer
      to those who missed appointments were prevalent, and favoured intervention
      strategies included punishing the patient in some way. Receptionists believed
      that general practitioners should address the issue of the missed appointment
      with the patient. General practitioners felt guarded about addressing missed
      appointments with their patients in case it affected the doctor-patient
      relationship. CONCLUSION: People who miss appointments were viewed negatively by
      primary care staff, and most of the reasons for missed appointments were focused
      on patients. These beliefs underpinned intervention strategies aimed mainly at
      punishment. Since there is no evidence base concerning interventions that are
      effective in reducing missed appointments, these negative attitudes may not be
      beneficial to staff or their patients.

PMID- 14965390
TI  - Factors influencing the uptake of childhood immunisation in rural areas.
AB  - BACKGROUND: Childhood vaccination has been vigorously debated in recent years.
      Professional and parental confidence in the measles, mumps and rubella (MMR)
      vaccine in particular has been shaken, as reflected by its decreased uptake. AIM:
      To investigate the influence of practice type and the method of vaccination
      call/recall on childhood immunisation coverage. DESIGN: Analysis of childhood
      immunisation uptake rates. SETTING: General practices in the Highland NHS Health
      Board area in Scotland. METHOD: Data on the immunisation uptake of individual
      practices in the region were obtained from the Information and Statistics
      Division of NHS Scotland. RESULTS: Uptake of all vaccines in children reaching
      the age of 2 years was lower in practices using their own call/recall system than
      those engaged with the national system. Inducement practices achieved lower
      uptake than non-inducement practices for every immunisation studied, with the
      differences ranging from 4.7% to 7.8%. Compared with group practices, uptake of
      all vaccines was less for single-handed practices, with the differences ranging
      from 2.4% to 11.4%. A logistic regression analysis found that high uptake of the
      diphtheria and meningococcus group C vaccines by the age of 24 months was
      significantly associated with use of the national call/recall system. Only
      inducement practice status was significantly associated with reduced uptake in
      children aged 12 months. CONCLUSIONS: Engagement with the national call/recall
      system was associated with higher immunisation coverage for children reaching the
      age of 2 years. Inducement status was associated with low uptake of vaccinations
      in children reaching the age of 1 year.

PMID- 14965391
TI  - Bacterial vaginosis and preterm birth: a prospective community-based cohort
      study.
AB  - BACKGROUND: Preterm birth before 37 weeks' gestation is associated with 70% of
      perinatal morbidity and nearly half of long-term neurological morbidity. Hospital
      based studies have shown that bacterial vaginosis is associated with preterm
      birth. AIM: To estimate the relative risk of preterm birth in women with and
      without bacterial vaginosis, detected by self-administered vaginal swab at < 10
      weeks' gestation. DESIGN: Prospective cohort study. SETTING: Thirty-two general
      practices and five family planning clinics in South London. PARTICIPANTS: A total
      of 1216 women with bacterial vaginosis status established before 10 weeks'
      gestation, by analysis of Gram stained vaginal smears by two independent
      observers. METHOD: All women who did not miscarry or have a termination of
      pregnancy before 16 weeks' gestation were sent a brief confidential questionnaire
      at 16 weeks and at term asking about pregnancy outcome. Data on non-responders
      were obtained by searches of hospital and general practice records and by
      telephone calls to patients. RESULTS: Ascertainment was 87% (937/1072). The mean
      age of the women was 31 years. Thirteen per cent (122/925) had bacterial
      vaginosis and 5% (44/897) had a spontaneous preterm birth. The relative risk (RR)
      of preterm birth in women with bacterial vaginosis was 0.9 (95% confidence
      interval [CI] = 0.4 to 2.2). However, bacterial vaginosis was associated with
      late miscarriage at 13-23 weeks (R = 4.0, 95%CI = 1.3 to 12.1). Preterm birth was
      not associated with previous preterm birth, black ethnicity, age < 20 years, low
      social class, single marital status, or chlamydial infection. However, it was
      more common in women who reported smoking in pregnancy (RR = 2.9, 95% CI = 1.5 to
      5.5). Of 867 responders, 552 (64%) said that providing a vaginal swab was at
      least as easy as providing a urine specimen. CONCLUSIONS: In this low-risk
      community-based cohort, bacterial vaginosis was not a strong risk factor for
      preterm birth.

PMID- 14965392
TI  - Referral letters to colorectal surgeons: the impact of peer-mediated feedback.
AB  - BACKGROUND: General practitioners (GPs) select few patients for specialist
      investigation. Having selected a patient, the GP writes a referral letter which
      serves primarily to convey concerns about the patient and offer background
      information. Referral letters to specialists sometimes provide an inadequate
      amount of information. The content of referral letters to colorectal surgeons can
      now be scored based on the views of GPs about the ideal content of referral
      letters. AIM: To determine if written feedback about the contents of GP referral
      letters mediated by local peers was acceptable to GPs and how this feedback
      influenced the content and variety of their referrals. DESIGN: A non-randomised
      control trial. SETTING: GPs in North Nottinghamshire. METHOD: In a controlled
      trial, 26 GPs were offered written feedback about the documented contents of
      their colorectal referral letters over 1 year. The feedback was designed and
      mediated by two nominated local GPs. The contents of referral letters were
      measured in the year before and 6 months after feedback. GPs were asked about the
      style of the feedback. The contents of referral letters and the proportion of
      patients with organic pathology were compared for the feedback GPs and other
      local GPs who could be identified as having used the same hospital for their
      referrals in the period before and after feedback. RESULTS: All GPs declared the
      method of feedback to be acceptable but raised concerns about their own
      performance, and some were upset by the experience. None withdrew from the
      project. There was a difference of 7.1 points (95% confidence interval = 1.9 to
      12.2) in the content scores between the feedback group and the controls after
      adjusting for baseline differences between the groups. Of the GPs who referred to
      the same hospital before and after feedback, the feedback GPs referred more
      patients with organic pathology than other local colleagues. CONCLUSIONS: GPs
      welcome feedback about the details appearing on their referral letters, although
      peer comparisons may not always lead to changes in practice. However, in some
      cases feedback improves the content of GP referral letters and may also impact on
      the type of patients referred for investigation by specialists.

PMID- 14965393
TI  - Validation of a method to establish practice-based stroke and TIA registers.
AB  - This study compares two methods to establish stroke and transient ischaemic
      attack (TIA) practice-based registers, which are of particular relevance to
      practices with limited diagnostic coding. Both arms involved a notes review of
      all patients taking antiplatelets or anticoagulants, and, either a further notes
      review of all patients with ischaemic heart disease (IHD) or diabetes (extensive
      arm), or asking about a history of stroke or TIA during IHD or diabetic clinics
      (pragmatic arm). The extensive arm involved searching 11% of the practice notes,
      whereas the pragmatic arm only involved 3% and had almost as high a yield. This
      study suggests that the pragmatic method could be used to help build practice
      based stroke and TIA registers.

PMID- 14965394
TI  - Airborne collapse: an in-flight emergency.

PMID- 14965395
TI  - Respiratory infection and antibiotic prescription rates.

PMID- 14965398
TI  - Diagnosing coughs and colds.

PMID- 14965399
TI  - Is dyspraxia a medical condition or a social disorder?

PMID- 14965400
TI  - Predicting complications from acute cough in pre-school children in primary care:
      a prospective cohort study.
AB  - BACKGROUND: There is uncertainty about which children with cough are most and
      least likely to experience complications. AIM: To derive a clinical prediction
      rule for complications in pre-school children presenting to primary care with
      acute cough. DESIGN OF STUDY: Prospective cohort study. SETTING: Eight general
      practices in Leicestershire, United Kingdom. METHOD: Pre-school children with
      cough for < or =28 days and without asthma were recruited. Sociodemographic,
      clinical history, and examination data were collected and univariable logistic
      regression used to explore the associations with complications. These were
      defined as any new symptom, sign or diagnosis identified by a primary care
      clinician at a parent initiated reconsultation, or hospital admission, before
      cough resolution. Those factors with stronger relationships (P< 0.2) were then
      modelled using multivariable logistic regression to identify the factors
      independently associated with complications. RESULTS: The pre-test probability of
      complications was 10%. On univariable analysis, fever (odds ratio [OR] = 4.86;
      95% confidence interval [CI] = 1.74 to 13.6), chest signs (OR = 2.72; CI = 1.06
      to 6.96), and tachypnoea (OR = 3.80; CI = 1.22 to 11.8) were associated with
      complications. On multivariable analysis, only fever (OR = 5.56; CI = 1.75 to
      17.6) and chest signs (OR = 2.88; CI = 1.02 to 8.05) were independently
      associated with complications. These ORs translate into post-test probabilities
      of complications of 6% for children with neither fever nor chest signs, 18% for
      children with chest signs, 28% for children with fever, and 40% for children with
      fever and chest signs. CONCLUSIONS: If validated, this clinical prediction rule
      could be used to individualise the management of acute cough in pre-school
      children.

PMID- 14965401
TI  - Pathogens involved in lower respiratory tract infections in general practice.
AB  - BACKGROUND: There are few investigations into the aetiology of lower respiratory
      tract infections (LRTIs) in general practice. AIM: To describe the aetiology of
      LRTI among adult patients in general practice in The Netherlands. DESIGN OF
      STUDY: Prospective observational study. SETTING: General practices in the Leiden
      region, The Netherlands. METHOD: Adult patients with a defined LRTI were
      included. Standard medical history and physical examination were performed.
      Sputum, blood and throat swabs were collected for diagnostic tests. Aetiological
      diagnosis, categorised as definite or possible, was based on the results of
      bacterial and viral cultures, serological techniques, and on polymerase chain
      reaction. Proportions of pathogens causing LRTI were assessed in relation to
      chest X-ray findings. RESULTS: A bacterial cause was established in 43 (30%), and
      a viral cause in 57 (39%) of the 145 patients with a LRTI. Influenza virus A was
      the most frequently diagnosed microorganism, followed by Haemophilus influenzae,
      and Mycoplasma pneumoniae. Streptococcus pneumoniae was found in 6% of the
      patients. CONCLUSIONS: Pathogens were found in two-thirds of the patients. In
      half of these patients there was a viral cause. Influenza virus A was the most
      frequently found pathogen. The treatment with antibiotics of at least one-third
      of the patients with LRTI was superfluous. This observation should result in
      changes in the prescription of antibiotics in LRTI.

PMID- 14965402
TI  - A diagnostic rule for the aetiology of lower respiratory tract infections as
      guidance for antimicrobial treatment.
AB  - BACKGROUND: The majority of patients with lower respiratory tract infections
      (LRTIs) are treated with antibiotics; some of them are unnecessary because of a
      viral cause. Information on prediction of the aetiology, especially in a general
      practice setting, is missing. AIM: To differentiate between viral and bacterial
      LRTI on simple clinical criteria, easily obtained at the bedside. DESIGN OF
      STUDY: Prospective observational study. SETTING: General practices in the Leiden
      region of The Netherlands. METHOD: Adult patients with LRTI were included.
      Standard medical history and physical examination were performed. Sputum, blood
      and throat swabs were collected for diagnostic tests. According to
      microbiological findings, patients were classified as bacterial, viral, dual
      infection and unknown cause. In a logistic regression model independent
      predictors were determined. Scoring systems were developed. The accuracies of the
      diagnostic rules were tested by using receiver operating characteristic (ROC)
      curves. RESULTS: One-hundred and forty-five patients were classified as having
      bacterial (n = 35), viral (n = 49), or dual infection (n = 8), or infection of
      unknown cause (n = 53), respectively. Independent predictors for bacterial
      infection were fever (odds ratio [OR] = 8.0; 95% confidence interval [CI] = 0.9
      to 71.0), headache (OR = 4.3; 95% CI = 1.0 to 19.1) cervical painful lymph nodes
      (OR = 8.7; 95% CI = 1.1 to 68.0), diarrhoea (OR = 0.3; 95% CI = 0.1 to 1.0) and
      rhinitis (OR = 0.3; 95% CI = 0.1 to 0.9). As an additional independent predictor,
      an infiltrate on chest X-ray (OR = 5.0; 95% CI = 1.2 to 20.5) was found. The
      diagnostic rules developed from these variables classified the aetiology of LRTI
      with a ROC curve area of 0.79 (clinical score), 0.77 (simplified score) and 0.83
      (extended score). CONCLUSIONS: A diagnostic rule was developed, based on
      information that is easy to obtain at the bedside, to predict a bacterial
      infection. This diagnostic rule may be a tool for general practitioners in their
      management of patients with LRTI.

PMID- 14965403
TI  - Qualitative study of men's perceptions of why treatment delays occur in the UK
      for those with testicular cancer.
AB  - BACKGROUND: Many studies (but not all) have shown that for men with testicular
      cancer a longer treatment delay is associated with additional treatments, greater
      morbidity, and shorter survival. AIM: This paper explores patients' perspectives
      on why treatment delays occur. DESIGN: Qualitative study using narrative
      interviews SETTING: Interviews in patient's homes throughout the United Kingdom
      (UK). METHOD: Interviews with a maximum variation sample of 45 men with
      testicular cancer, recruited through general practitioners (GPs), urologists,
      support groups, and charities. RESULTS: Those who sought help relatively quickly
      responded to symptoms, had heard about testicular cancer in the media, had seen
      leaflets in GPs' surgeries, or knew others with this disease. Men delayed because
      they did not recognise signs and symptoms; feared appearing weak, a
      hypochondriac, or lacking in masculinity; recalled past illness or painful
      examinations; were embarrassed; feared the consequences of treatment; or lacked
      time to consult their doctors. Beliefs about symptoms and pessimistic
      associations with cancer also led to delay. Treatment delays also resulted from
      misdiagnosis or waiting lists. CONCLUSION: Whether or not men should be taught to
      examine themselves routinely to check for testicular cancer is much debated. This
      study suggests that it is important that men are aware of the normal shape and
      feel of their testicles, and may benefit from information about signs and
      symptoms of testicular cancer and the excellent cure rate. Information, provided
      in surgeries where men feel welcome, might encourage men to seek help promptly
      when a problem arises. Our study also suggests that GPs may need to accept a low
      threshold for ultrasound investigation of testicular symptoms and that the
      ultrasound service needs to be improved. These measures may further reduce
      mortality and morbidity.

PMID- 14965404
TI  - Implementation of RCGP guidelines for acute low back pain: a cluster randomised
      controlled trial.
AB  - BACKGROUND: The Royal College of General Practitioners (RCGP) has produced
      guidelines for the management of acute low back pain in primary care. AIM: To
      investigate the impact on patient management of an educational strategy to
      promote these guidelines among general practitioners (GPs). DESIGN OF STUDY:
      Group randomised controlled trial, using the health centre as the unit of
      randomisation. SETTING: Primary care teams in north-west England. METHOD: Twenty
      four health centres were randomly allocated to an intervention or control arm.
      Practices in the intervention arm were offered outreach visits to promote
      national guidelines on acute low back pain, as well as access to fast-track
      physiotherapy and to a triage service for patients with persistent symptoms.
      RESULTS: Twenty-four centres were randomised. Two thousand, one hundred and
      eighty-seven eligible patients presented with acute low back pain during the
      study period: 1049 in the intervention group and 1138 in the control group. There
      were no significant differences between study groups in the proportion of
      patients who were referred for X-ray, issued with a sickness certificate,
      prescribed opioids or muscle relaxants, or who were referred to secondary care,
      but significantly more patients in the intervention group were referred to
      physiotherapy or the back pain unit (difference in proportion = 12.2%, 95%
      confidence interval [CI] = 2.8% to 21.6%). CONCLUSION: The management of patients
      presenting with low back pain to primary care was mostly unchanged by an outreach
      educational strategy to promote greater adherence to RCGP guidelines among GPs.
      An increase in referral to physiotherapy or educational programmes followed the
      provision of a triage service.

PMID- 14965405
TI  - Patients' experiences when accessing their on-line electronic patient records in
      primary care.
AB  - BACKGROUND: Patient access to on-line primary care electronic patient records is
      being developed nationally. Knowledge of what happens when patients access their
      electronic records is poor. AIM: To enable 100 patients to access their
      electronic records for the first time to elicit patients' views and to understand
      their requirements. DESIGN OF STUDY: In-depth interviews using semi-structured
      questionnaires as patients accessed their electronic records, plus a series of
      focus groups. SETTING: Secure facilities for patients to view their primary care
      records privately. METHOD: One hundred patients from a randomised group viewed
      their on-line electronic records for the first time. The questionnaire and focus
      groups addressed patients' views on the following topics: ease of use;
      confidentiality and security; consent to access; accuracy; printing records;
      expectations regarding content; exploitation of electronic records; receiving new
      information and bad news. RESULTS: Most patients found the computer technology
      used acceptable. The majority found viewing their record useful and understood
      most of the content, although medical terms and abbreviations required
      explanation. Patients were concerned about security and confidentiality,
      including potential exploitation of records. They wanted the facility to give
      informed consent regarding access and use of data. Many found errors, although
      most were not medically significant. Many expected more detail and more
      information. Patients wanted to add personal information. CONCLUSION: Patients
      have strong views on what they find acceptable regarding access to electronic
      records. Working in partnership with patients to develop systems is essential to
      their success. Further work is required to address legal and ethical issues of
      electronic records and to evaluate their impact on patients, health professionals
      and service provision.

PMID- 14965406
TI  - Increased personal medication use among Finnish physicians from 1986 to 1997.
AB  - This study was based on a nationwide survey of 2671 Finnish physicians in 1986
      and 3313 in 1997. The results showed that the proportion of physicians who often
      or regularly reported using any medication increased significantly from 1986 to
      1997 (men 27.8% versus 44.3%, P = 0.001; women 28.8% versus 48.6%, P = 0.001).
      Among the general practitioners working in the public sector, the increase was
      from 31.2% to 49.3%. Gastrointestinal diseases (74%), asthma (63%) and mental
      disorders (62%) were the most commonly self-medicated conditions in 1997.

PMID- 14965407
TI  - Saturday surgeries--do patients feel their needs can be met by alternative out-of
      hours care? A questionnaire study.
AB  - There is a trend in the United Kingdom (UK) towards using out-of-hours cover to
      replace Saturday surgeries. This study asks patients their views about
      alternative cover. Seventy-five questionnaires were collected from 125 patients
      attending Saturday surgery sessions (response rate = 60%) over 6 weeks. Sixty
      four (85.3%) patients felt they needed urgent attention, and 64 (85.3%) felt that
      any of the doctors could deal with them. The most popular alternatives were
      routine appointments and being seen by the deputising doctor, both of which were
      preferred by 20 (26.7%) patients. Changing Saturday surgeries to using deputising
      cover is, on the whole, acceptable to patients.

PMID- 14965408
TI  - The space of our lives.

PMID- 14965409
TI  - Solutions and challenges in sample preparation for chromatography.
AB  - Sample preparation as practiced today in analytical laboratories is a complex
      combination of classical and modern techniques. In this review, the progress made
      in the last few years in sample preparation for chromatography is examined and
      discussed in comparison with previous achievements in the field. Discovery and
      development of new materials is seen as one of the main sources of progress, but
      finding better ways of using the old principles and the improvements in
      technology are also major contributing factors for advancement. Practical demands
      for analysis of pharmaceutical products, the environmental studies, and life
      science are the main driving forces for development in sample preparation for
      chromatography.

PMID- 14965410
TI  - Studies of the thermal degradation of acetaminophen using a conventional HPLC
      approach and electrospray ionization-mass spectrometry.
AB  - The thermal degradation of acetaminophen is studied via conventional accelerated
      aging studies by initially thermally stressing the compound at temperatures
      between 160 degrees C and 190 degrees C and measuring the rate of decomposition
      by reversed-phase high-performance liquid chromatography. Rates of decomposition
      of the compound in the dry state and the activation energy for the process are
      determined and compared with previously published kinetic and thermodynamic data
      for the degradation of acetaminophen in solution. In addition, the thermal
      fragmentation of acetaminophen under electrospray ionization (ESI) conditions
      using an interface with a heated capillary inlet is studied and the apparent
      activation energy for this process also is characterized. A comparison of the
      data shows that acetaminophen is significantly more stable in the dry state than
      in solution. However, the gas-phase fragmentation of acetaminophen under ESI
      conditions occurs more readily than either dry- or solution-state degradation.
      Although the resulting electrospray fragmentation mimics the breakdown product
      that is formed when the compound undergoes either acid or base catalyzed
      hydrolysis in aqueous solutions, the mechanism that produces the fragment ion
      appears to involve a two-step process. Initially, the parent ion forms of the
      analyte are produced in the spray region of the interface followed by wall
      catalyzed decomposition and re-ionization in the heated inlet capillary of the
      spectrometer.

PMID- 14965411
TI  - Chiral separation of deprenyl-N-oxide isomers by capillary electrophoresis using
      various cyclodextrin derivatives.
AB  - Chiral separation of deprenyl-N-oxide isomers is presented using capillary
      electrophoresis in the presence of various cyclodextrin (CD) derivatives. This
      recently identified metabolite of R-(-)-deprenyl may possess desirable
      pharmacological activities. The effect of the cavity size and the substituents of
      the CD are examined on the enantiomer resolution of the compound having an
      asymmetric center on a heteroatom. The importance of hydrophilic or hydrogen
      bonding interaction, as well as the position of the interacting groups is
      demonstrated. Outstanding selectivity and resolution values are achieved using
      the chargeable carboxymethyl-beta-CD. 2-Hydroxypropyl-beta-CD is also suitable
      for the enantiomer separation of the analyte. Native beta-CD and carboxyethyl
      beta-CD provide only poor enantioselectivity, whereas heptakis-(2,6-di-O-methyl)
      beta-CD is capable of separating only the diastereomers. No chiral resolution can
      be observed in the presence of gamma-CD.

PMID- 14965412
TI  - Simultaneous high-performance liquid chromatographic determination of
      pioglitazone and metformin in pharmaceutical-dosage form.
AB  - A simple, rapid, and precise method is developed for the quantitative
      simultaneous determination of metformin and pioglitazone in a combined
      pharmaceutical-dosage form. Separation is achieved with a Zorbax XDB C(18), 15-cm
      analytical column using buffer-acetonitrile (66:34, v/v) of pH 7.1, adjusted with
      orthophosphoric acid as the mobile phase. The buffer used in the mobile phase
      contains 10mM disodium hydrogen phosphate and 5mM sodium dodecyl sulphate in
      double-distilled water. The instrumental settings are flow rate of 1 mL/min,
      column temperature at 40 degrees C, and detector wavelength of 226 nm. The
      internal standard method is used for the quantitation of the ingredients of this
      combination. Methylparaben is used as an internal standard. The method is
      validated and shown to be linear for metformin and pioglitazone. The correlation
      coefficients for metformin and pioglitazone are 0.9991 and 0.9999, respectively.
      The relative standard deviations for six replicate measurements in two sets of
      each drug in the tablets are always less than 2%.

PMID- 14965413
TI  - High-performance liquid chromatographic stationary phases based on silica coated
      by in situ polymerization of a methacryloyl beta-cyclodextrin monomer: synthesis,
      characterization, and chromatographic evaluation.
AB  - Porous silica beads have been coated with a 2-hydroxy-3-methacryloyloxypropyl
      beta-cyclodextrin polymer by in situ free-radical polymerization in water. This
      system has been developed for use as a stationary phase in high-performance
      liquid chromatography. In the conditions used, the coating efficiency is
      controlled by the initial concentration of the monomer. The polymer coating has
      been quantitated by thermogravimetric analysis. The stationary phases have also
      been characterized by means of the nitrogen adsorption/desorption method, energy
      dispersion X-ray analysis, and scanning electron microscopy to investigate the
      changes in the porosity, as well as in the surface properties generated by the
      coating process. Finally, the chromatographic evaluation has been made under
      normal- and reversed-phase elution conditions.

PMID- 14965414
TI  - Determination of vitamin E acid succinate in biodegradable microspheres by
      reversed-phase high-performance liquid chromatography.
AB  - A simple, rapid, and reproducible reversed-phase high-performance liquid
      chromatographic (HPLC) method is applied to the routine assay of vitamin E acid
      succinate in biodegradable microspheres. Vitamin E acid-succinate-containing poly
      (D,L-lactic-co-glycolic acid) microspheres are prepared by the solvent
      evaporation method. The starting drug-polymer ratio is 1:10 (w/w) and the total
      amount of drug and polymer processed is always 440 mg. The content of vitamin E
      acid succinate in the microspheres is evaluated by HPLC. Chromatography is
      carried out isocratically at 25 degrees C +/- 0.5 degrees C on an Extrasil ODS-2
      column with a mobile phase composed of methanol-water (97:3, v/v) (pH 5.6) at a
      flow rate of 2 mL/min and UV detection at 284 nm. Parameters such as linearity,
      limits of quantitation (LOQ) and detection (LOD), precision, accuracy, recovery,
      specificity, and ruggedness are studied as reported in the International
      Conference on Harmonization guidelines. The stability of vitamin E acid succinate
      is also studied with satisfactory results after 48 h at 25 degrees C. The method
      is selective and linear for drug concentrations in the range 15-210 micro g/mL.
      The LOQ and LOD are 15 and 3 micro g/mL, respectively. The results for accuracy
      studies are good. Values for coefficient of variation for intra- and interassay
      are 2.08% and 2.32%, respectively. The mean percentage of vitamin E acid
      succinate in the recovery studies is 99.52% +/- 0.81%. The mean loading
      efficiency for microspheres is 96.53% +/- 1.31%.

PMID- 14965415
TI  - Detection of tinuvin 770, a light stabilizer of plastic materials from dialysis
      membranes, by high-performance liquid chromatographic analysis.
AB  - Tinuvin 770 [bis(2,2,6,6-tetramethyl-4-piperidinyl)sebacate] is a
      pharmacologically active agent used worldwide as a light stabilizer for plastic
      materials. In vitro studies show that it is an L-type Ca(2+) channel and neuronal
      nicotic acethylcholine receptor blocker. Hypotension, vegetative dysfunction, and
      neurological symptoms are frequently observed during a haemodialysis treatment.
      The release of Tinuvin 770 from plastic materials applied in haemodialysis may
      play a part in the development of clinical signs. In our study, four different
      commonly used haemodialysis membranes (polysulphon, cuprophan, and two types of
      hemophan) are examined. The polymers are soaked for 72 h in physiological saline
      solution. Isolation is carried out using a Waters Oasis SPE column for solid
      phase extraction and by high-performance liquid chromatography (HPLC) with
      electrospray ionization-mass spectrometric detection. Tinuvin 770 release is
      detected from all examined membranes. Validation studies show a satisfactory
      selectivity, linearity, accuracy, and recovery of this method. Our results
      suggest that Tinuvin 770 could have specific toxicological and therapeutic
      importance related to haemodialysis treatment. The developed HPLC method is
      suitable for the detection of Tinuvin 770.

PMID- 14965430
TI  - The Matrix Method of literature reviews.

PMID- 14965431
TI  - Setting objectives for community and systems change: an application of concept
      mapping for planning a statewide health improvement initiative.
AB  - The Hawaii Department of Health (HDOH) used concept mapping techniques to engage
      local stakeholders and national subject area experts in defining the community
      and system factors that affect individuals' behaviors related to tobacco,
      nutrition, and physical activity. Over eight working days, project participants
      brainstormed 496 statements (edited to a final set of 90), which were then sorted
      and rated for their importance and feasibility. A sequence of multivariate
      statistical analyses, including multidimensional scaling and hierarchical cluster
      analysis, generated maps and figures that were then interpreted by project
      stakeholders. The results were immediately incorporated into an official plan,
      approved by the governor and state legislature, recommending how Hawaii's tobacco
      settlement resources could be used to create sustainable changes in population
      health. The results also provide empirical support for the premise that both
      community and systems factors ought to be considered when planning comprehensive
      health improvement initiatives.

PMID- 14965432
TI  - The evolution of health education: the Kaiser Permanente Southern California
      experience.
AB  - This article conveys the history of establishing the health education program,
      the current delivery model, and the lessons learned from the process including
      practical applications for the practice setting. The evolution of health
      education in Kaiser Permanente reflects its history and describes the continued
      need for and relevance of health education. The era of the patient as the passive
      recipient of care is being replaced by an emphasis on the patient as a partner in
      care. Every health education program emphasizes shared responsibility and
      encourages active participation by the patient, family, and other social
      supports. Multiple modalities of self-care and/or self-management resources and
      services increase member access to needed health education, health promotion, and
      prevention information that facilitate lifestyle behavior changes for better
      health and simultaneously improve organizational clinical outcome measures.
      Ongoing efforts align health education with regulatory requirements and the
      organization's commitment to culturally and linguistically appropriate patient
      information.

PMID- 14965433
TI  - Taking the path less traveled: the nontraditional doctorate.
AB  - There are a number of options available for those who wish to pursue a doctoral
      degree. In addition to the traditional method of attending classes at a brick and
      mortar institution, this article describes two of those options. One is a
      combination of the traditional and nontraditional Internet and on-line approach.
      The other is a nontraditional route to the doctorate that is completely Internet
      based. Both options have merits and suit different people for different reasons.
      This article describes each of these alternative routes to the doctorate through
      the words and experiences of two professionals who have followed paths less
      traveled.

PMID- 14965434
TI  - The costs and benefits to participants in community partnerships: a paradox?
AB  - This article examines the degree of stakeholder participation in health and
      social partnership schemes in relation to their perceptions of benefits, costs,
      satisfaction, commitment, and ownership. The findings suggest that (a)
      involvement, commitment, and sense of ownership were invariably associated with
      high benefits and mostly with low costs; (b) benefits, commitment, and ownership
      might be more sensitive monitors of involvement than costs and satisfaction; (c)
      an increase in involvement was initially associated with decreased costs and
      increased satisfaction up to a point beyond which costs increased and
      satisfaction decreased despite increasing benefits; and (d) favorable cost
      benefit ratios were perceived when the benefits were at least 1.6 times the
      costs. Partnership initiatives need to explore the involvement "cut-off" point at
      which the costs (and satisfaction) might change direction. For favorable cost
      benefit ratios, benefits need to be at least 60% more than costs (Ansari's
      paradox).

PMID- 14965435
TI  - Engaging youth through photovoice.
AB  - The photovoice process aims to use photographic images taken by persons with
      little money, power, or status to enhance community needs assessments, empower
      participants, and induce change by informing policy makers of community assets
      and deficits. This article describes a youth photovoice project implemented in an
      after-school program that attempted to adapt the photovoice method to youth
      participants, test the effectiveness of the method with youth, and develop and
      refine a curriculum for replication. A process such as photovoice provides youth
      the opportunity to develop their personal and social identities and can be
      instrumental in building social competency. Youth should and need to be given the
      opportunity to build and confirm their abilities, to comment on their experiences
      and insights, and to develop a social morality for becoming a positive agent
      within their communities and society. For more examples of photos taken by the
      youth during this project, visit http://www.jhsph.edu/youthphotovoice.

PMID- 14965436
TI  - Using multilevel, multisource needs assessment data for planning community
      interventions.
AB  - African Americans and Latinos share higher rates of cardiovascular disease (CVD)
      and diabetes compared with Whites. These diseases have common risk factors that
      are amenable to primary and secondary prevention. The goal of the Chicago REACH
      2010-Lawndale Health Promotion Project is to eliminate disparities related to CVD
      and diabetes experienced by African Americans and Latinos in two contiguous
      Chicago neighborhoods using a community-based prevention approach. This article
      shares findings from the Phase 1 participatory planning process and discusses the
      implications these findings and lessons learned may have for programs aiming to
      reduce health disparities in multiethnic communities. The triangulation of data
      sources from the planning phase enriched interpretation and led to more creative
      and feasible suggestions for programmatic interventions across the four levels of
      the ecological framework. Multisource data yielded useful information for program
      planning and a better understanding of the cultural differences and similarities
      between African Americans and Latinos.

PMID- 14965437
TI  - Using scenario planning in public health: anticipating alternative futures.
AB  - Scenario planning is a method for anticipating possible alternative futures. Used
      widely in business applications, it allows planners to anticipate problems,
      reevaluate assumptions, and reflect on consequences of those alternative futures.
      In this article, scenario planning is applied to public health, specifically to
      illustrate the four steps in scenario planning for public health using a health
      department's desire to address chronic disease prevention and control. An
      unhealthy diet and physical inactivity are considered to be key risk factors. The
      scenarios are presented in table format and are for illustration purposes only.
      Many other plausible scenarios could be constructed. Scenario planning allows
      stake-holders to define a desired, shared vision of the future, but more
      important, they can better prepare public health professionals to be successful
      in a constantly changing environment.

PMID- 14965438
TI  - Development of a cervical cancer educational program for Chinese women using
      intervention mapping.
AB  - This article describes the development of a program to increase Pap screening
      behavior among women in Taiwan. Intervention mapping, an innovative process of
      intervention design, guided the development of this program. The development
      process included a needs assessment identifying factors influencing Pap screening
      behavior relevant to Chinese women. The program used methods such as information
      transmission, modeling, persuasion, and facilitation. Strategies included direct
      mail communication, role-model stories and testimonials, and a telephone
      counseling component. The delineation of specific plans for implementation and
      evaluation are also described.

PMID- 14965439
TI  - Application of the transtheoretical model to health education for older adults.
AB  - The application of theory to practice can be challenging. This article describes
      the experiences of one organization in applying the Transtheoretical Model (TTM)
      to a health promotion program for older adults, Health Stages. The concepts of
      the model, especially stage of change, were successfully used for program
      planning, curriculum development, and program evaluation. A Programming Grid was
      developed to guide curriculum development and evaluate if programs were reaching
      out to people at all stages of readiness to make healthy changes. Other TTM
      constructs, including self-efficacy, decisional balance, and processes of change
      were incorporated into the Health Stages curriculum. Evaluation showed that the
      pilot sites increased their offering of action- and maintenance-oriented
      programs, filling in the gaps in current programming. Older adults were receptive
      and interested in the model. The TTM enhanced the program by providing a
      framework for design and a method for reaching a wider audience of older adults
      with important health information.

PMID- 14965440
TI  - Bypass of tumor drug resistance by antivascular therapy.
AB  - Multidrug resistance (MDR) presents a major obstacle for the successful
      chemotherapy of cancer. Its emergence during chemotherapy is attributed to a
      selective process, which gives a growth advantage to MDR cells within the
      genetically unstable neoplastic cell population. The pleiotropic nature of
      clinical MDR poses a great difficulty for the development of treatment strategies
      that aim at blocking MDR at the tumor cell level. Targeting treatment to the
      nonmalignant vascular network-the lifeline of the tumor-is a promising
      alternative for the treatment of drug-resistant tumors. The present study
      demonstrates that MDR in cancer can be successfully circumvented by photodynamic
      therapy (PDT) using an antivascular treatment protocol. We show that, although P
      glycoprotein-expressing human HT29/MDR colon carcinoma cells in culture are
      resistant to PDT with Pd-bacteriopheophorbide (TOOKAD), the same treatment
      induces tumor necrosis with equal efficacy (88% vs 82%) in HT29/MDR-derived
      xenografts and their wild type counterparts, respectively. These results are
      ascribed to the rapid antivascular effects of the treatment, supporting the
      hypothesis that MDR tumors can be successfully eradicated by indirect approaches
      that bypass their inherent drug resistance. We suggest that with progress in
      ongoing clinical trials, TOOKAD-PDT may offer a novel option for local treatment
      of MDR tumors.

PMID- 14965441
TI  - Poorly differentiated breast carcinoma is associated with increased expression of
      the human polycomb group EZH2 gene.
AB  - Polycomb group (PcG) genes contribute to the maintenance of cell identity, cell
      cycle regulation, and oncogenesis. We describe the expression of five PcG genes
      (BMI-1, RING1, HPC1, HPC2, and EZH2) innormal breast tissues, invasive breast
      carcinomas, and their precursors. Members of the HPC-HPH/PRC1 PcG complex,
      including BMI-1, RING1, HPC1, and HPC2, were detected in normal resting and
      cycling breast cells. The EED-EZH/PRC2 PcG complex protein EZH2 was only found in
      rare cycling cells, whereas normal resting breast cells were negative for EZH2.
      PcG gene expression patterns in ductal hyperplasia (DH), well-differentiated
      ductal carcinoma in situ (DCIS), and well-differentiated invasive carcinomas
      closely resembled the pattern in healthy cells. However, poorly differentiated
      DCIS and invasive carcinomas frequently expressed EZH2 in combination with HPC
      HPH/PRC1 proteins. Most BMI-1/EZH2 double-positive cells in poorly differentiated
      DCIS were resting. Poorly differentiated invasive carcinoma displayed an enhanced
      rate of cell division within BMI-1/EZH2 double-positive cells. We propose that
      the enhanced expression of EZH2 in BMI-1(+) cells contributes to the loss of cell
      identity in poorly differentiated breast carcinomas, and that increased EZH2
      expression precedes high frequencies of proliferation. These observations suggest
      that deregulated expression of EZH2 is associated with loss of differentiation
      and development of poorly differentiated breast cancer in humans.

PMID- 14965442
TI  - ING-1(heMAb), a monoclonal antibody to epithelial cell adhesion molecule,
      inhibits tumor metastases in a murine cancer model.
AB  - ING-1(heMAb), a human-engineered monoclonal antibody (MAb) that specifically
      targets the epithelial cell adhesion molecule (Ep-CAM), kills adenocarcinoma
      cells in vitro and inhibits tumor growth in vivo. In the current study, we
      evaluated the efficacy of ING-1(heMAb) in a murine model of cancer metastases.
      Mice received intravenous dosing of 1 mg/kg ING-1(heMAb), twice a week, starting
      on day 2 or day 5. A negative control group received 1 mg/kg human immunoglobulin
      G with the same dose frequency starting on day 2. A positive control group
      received weekly 100 mg/kg 5-flurouracil/leucovorin starting on day 2. ING
      1(heMAb)/day 2 treatment significantly reduced both the number of visible tumor
      nodules in body cavities (P <.01) and the number of metastases on lung surfaces
      (P <.005). The treatment also resulted in a 91% reduction of micrometastases in
      lung tissues (P <.0001). Delaying ING-1(heMAb) treatment until day 5 caused 54%
      reduction in micrometastases (P <.005). Our results indicate that a number of
      parameters, including treatment starting day, dose level, and dose frequency, are
      critical in achieving the optimal efficacy of ING-1(heMAb). We conclude that ING
      1(heMAb) effectively reduced tumor metastases in a murine cancer model.
      Immunotherapy with ING-1(heMAb) may be beneficial in treating human metastatic
      diseases.

PMID- 14965443
TI  - The transferrin receptor: a potential molecular imaging marker for human cancer.
AB  - Noninvasive imaging of differences between the molecular properties of cancer and
      normal tissue has the potential to enhance the detection of tumors. Because
      overexpression of endogenous transferrin receptor (TfR) has been qualitatively
      described for various cancers and is presumably due to malignant transformation
      of cells, TfR may represent a suitable target for application of molecular
      imaging technologies to increase detection of smaller tumors. In the work
      reported here, investigation into the biology of this receptor using electron
      microscopy has demonstrated that iron oxide particles targeted to TfR are
      internalized and accumulate in lysosomal vesicles within cells. Biochemical
      analysis of the interaction of imaging probes with cells overexpressing the TfR
      demonstrated that the extent of accumulation, and therefore probe efficacy, is
      dependent on the nature of the chemical cross-link between transferrin and the
      iron oxide particle. These data were utilized to design and synthesize an
      improved imaging probe. Experiments demonstrate that the novel magnetic resonance
      imaging (MRI) probe is sensitive enough to detect small differences in endogenous
      TfR expression in human cancer cell lines. Quantitative measurement of TfR
      overexpression in a panel of 27 human breast cancer patients demonstrated that
      74% of patient cancer tissues overexpressed the TfR and that the sensitivity of
      the new imaging agent was suitable to detect TfR overexpression in greater than
      40% of these cases. Based on a biochemical and cell biological approach, these
      studies have resulted in the synthesis and development of an improved MRI probe
      with the best in vitro and in vivo imaging properties reported to date.

PMID- 14965444
TI  - Mutant K-ras regulates cathepsin B localization on the surface of human
      colorectal carcinoma cells.
AB  - Cathepsin B protein and activity are known to localize to the basal plasma
      membrane of colon carcinoma cells following the appearance of K-ras mutations.
      Using immunofluorescence and subcellular fractionation techniques and two human
      colon carcinoma cell lines - one with a mutated K-ras allele (HCT 116) and a
      daughter line in which the mutated allele has been disrupted (HKh-2)-we
      demonstrate that the localization of cathepsin B to caveolae on the surface of
      these carcinoma cells is regulated by mutant K-ras. In HCT 116 cells, a greater
      percentage of cathepsin B was distributed to the caveolae, and the secretion of
      cathepsin B and pericellular (membrane-associated and secreted) cathepsin B
      activity were greater than observed in HKh-2 cells. Previous studies established
      the light chain of annexin II tetramer, p11, as a binding site for cathepsin B on
      the surface of tumor cells. The deletion of active K-ras in HKh-2 cells reduced
      the steady-state levels of p11 and caveolin-1 and the distribution of p11 to
      caveolae. Based upon these results, we speculate that cathepsin B, a protease
      implicated in tumor progression, plays a functional role in initiating
      proteolytic cascades in caveolae as downstream components of this cascade (e.g.,
      urokinase plasminogen activator and urokinase plasminogen activator receptor) are
      also present in HCT 116 caveolae.

PMID- 14965445
TI  - A unique model system for tumor progression in GBM comprising two developed human
      neuro-epithelial cell lines with differential transforming potential and
      coexpressing neuronal and glial markers.
AB  - The molecular mechanisms involved in tumor progression from a low-grade
      astrocytoma to the most malignant glioblastoma multiforme (GBM) have been
      hampered due to lack of suitable experimental models. We have established a model
      of tumor progression comprising of two cell lines derived from the same
      astrocytoma tumor with a set of features corresponding to low-grade glioma (as in
      HNGC-1) and high-grade GBM (as in HNGC-2). The HNGC-1 cell line is slow-growing,
      contact-inhibited, nontumorigenic, and noninvasive, whereas HNGC-2 is a rapidly
      proliferating, anchorage-independent, highly tumorigenic, and invasive cell line.
      The proliferation of cell lines is independent of the addition of exogenous
      growth factors. Interestingly, the HNGC-2 cell line displays a near-haploid
      karyotype except for a disomy of chromosome 2. The two cell lines express the
      neuronal precursor and progenitor markers vimentin, nestin, MAP-2, and NFP160, as
      well as glial differentiation protein S100beta. The HNGC-1 cell line also
      expresses markers of mature neurons like Tuj1 and GFAP, an astrocytic
      differentiation marker, hence contributing toward a more morphologically
      differentiated phenotype with a propensity for neural differentiation in vitro.
      Additionally, overexpression of epidermal growth factor receptor and c-erbB2, and
      loss of fibronectin were observed only in the HNGC-2 cell line, implicating the
      significance of these pathways in tumor progression. This in vitro model system
      assumes importance in unraveling the cellular and molecular mechanisms in
      differentiation, transformation, and gliomagenesis.

PMID- 14965446
TI  - Extracellular acidification alters lysosomal trafficking in human breast cancer
      cells.
AB  - Cancer cells invade by secreting degradative enzymes, which are sequestered in
      lysosomal vesicles. In this study, the impact of an acidic extracellular
      environment on lysosome size, number, and distance from the nucleus in human
      mammary epithelial cells (HMECs) and breast cancer cells of different degrees of
      malignancy was characterized because the physiological microenvironment of tumors
      is frequently characterized by extracellular acidity. An acidic extracellular pH
      (pH(e)) resulted in a distinct shift of lysosomes from the perinuclear region to
      the cell periphery irrespective of the HMECs' degree of malignancy. With
      decreasing pH, larger lysosomal vesicles were observed more frequently in highly
      metastatic breast cancer cells, whereas smaller lysosomes were observed in poorly
      metastatic breast cancer cells and HMECs. The number of lysosomes decreased with
      acidic pH values. The displacement of lysosomes to the cell periphery driven by
      extracellular acidosis may facilitate exocytosis of these lysosomes and increase
      secretion of degradative enzymes. Filopodia formations, which were observed more
      frequently in highly metastatic breast cancer cells maintained at acidic pH(e),
      may also contribute to invasion.

PMID- 14965447
TI  - High-resolution longitudinal screening with magnetic resonance imaging in a
      murine brain cancer model.
AB  - One of the main limitations of intracranial models of diseases is our present
      inability to monitor and evaluate the intracranial compartment noninvasively over
      time. Therefore, there is a growing need for imaging modalities that provide
      thorough neuropathological evaluations of xenograft and transgenic models of
      intracranial pathology. In this study, we have established protocols for multiple
      mouse magnetic resonance imaging (MRI) to follow the growth and behavior of
      intracranial xenografts of gliomas longitudinally. We successfully obtained
      weekly images on 16 mice for a total of 5 weeks on a 7-T multiple-mouse MRI. T2-
      and T1-weighted imaging with gadolinium enhancement of vascularity was used to
      detect tumor margins, tumor size, and growth. These experiments, using 3D whole
      brain images obtained in four mice at once, demonstrate the feasibility of
      obtaining repeat radiological images in intracranial tumor models and suggest
      that MRI should be incorporated as a research modality for the investigation of
      intracranial pathobiology.

PMID- 14965450
TI  - The effects of background noise on cognitive performance during a 70 hour
      simulation of conditions aboard the International Space Station.
AB  - A total of twenty-five subjects were cloistered for a period of 70 hours, five at
      a time, in a hyperbaric chamber modified to simulate the conditions aboard the
      International Space Station (ISS). A recording of 72 dBA background noise from
      the ISS service module was used to simulate noise conditions on the ISS. Two
      groups experienced the background noise throughout the experiment, two other
      groups experienced the noise only during the day, and one control group was
      cloistered in a quiet environment. All subjects completed a battery of cognitive
      tests nine times throughout the experiment. The data showed little or no effect
      of noise on reasoning, perceptual decision-making, memory, vigilance, mood, or
      subjective indices of fatigue. Our results suggest that the level of noise on the
      space station should not affect cognitive performance, at least over a period of
      several days.

PMID- 14965448
TI  - Exceptionally high protection of photocarcinogenesis by topical application of (-
      )-epigallocatechin-3-gallate in hydrophilic cream in SKH-1 hairless mouse model:
      relationship to inhibition of UVB-induced global DNA hypomethylation.
AB  - (--)-Epigallocatechin-3-gallate (EGCG) has been shown to have potent
      antiphotocarcinogenic activity, but it was required to develop a cream-based
      formulation for topical application. For topical application, we tested
      hydrophilic cream as a vehicle for EGCG. Treatment with EGCG ( approximately 1
      mg/cm(2) skin area) in hydrophilic cream resulted in exceptionally high
      protection against photocarcinogenesis when determined in terms of tumor
      incidence, tumor multiplicity, and tumor size in a SKH-1 hairless mouse model.
      EGCG also inhibited malignant transformation of ultraviolet B (UVB)-induced
      papillomas to carcinomas. In order to determine the mechanism of prevention of
      photocarcinogenesis, we determined the effect of EGCG on global DNA methylation
      pattern using monoclonal antibodies against 5-methyl cytosine and DNA
      methyltransferase in the long-term UV-irradiated skin because altered DNA
      methylation silencing is recognized as a molecular hallmark of human cancer. We
      found that treatment with EGCG resulted in significant inhibition of UVB-induced
      global DNA hypomethylation pattern. Long-term application of EGCG did not show
      any apparent sign of toxicity in mice when determined in terms of skin
      appearance, lean mass, total bone mineral content, and total bone mineral density
      but showed reduction in fat mass when analyzed using dual-energy X-ray
      absorptiometry. These data suggest that hydrophilic cream could be a suitable
      vehicle for topical application of EGCG, and that EGCG is a promising candidate
      for future cancer therapies based on its influence on the epigenetic pathway.

PMID- 14965451
TI  - An approach to the development of hearing standards for hearing-critical jobs.
AB  - Many jobs at the Department of Fisheries and Oceans Canada (DFO) have several
      features in common: they are often performed in noisy environments and involve a
      number of auditory skills and abilities, such as speech communication, sound
      localization, and sound detection. If an individual lacks these skills and
      abilities, it may constitute a safety risk for this individual, as well as for
      fellow workers and the general public. A number of scientific models have been
      developed to predict performance on these auditory skills based on diagnostic
      measures of hearing such as pure-tone audiograms. While these models have
      significant scientific and research value, they are unable to provide accurate
      predictions of real life performance on auditory skills necessary to perform
      hearing-critical jobs. An alternative and more accurate approach has been
      developed in this research project. A direct measure of functional speech
      perception in noise (Hearing in Noise Test: HINT) has been identified and
      validated for use in screening applicants for hearing-critical jobs in DFO. This
      screening tool has adequate and well-defined psychometric properties (e.g.
      reliability, sensitivity, and validity) so that screening test results can be
      used to predict an individual's ability to perform critical auditory skills in
      noisy environments, with a known degree of prediction error. Important issues
      must be considered when setting screening criteria. First, the concept of hearing
      critical tasks must be reviewed, since these tasks are often performed in high
      noise levels where normally-hearing people cannot hear adequately. Second, noise
      induced hearing loss is frequent in these noisy environments, and workers who
      acquire a hearing loss might not continue to meet the minimal auditory screening
      criteria throughout their career. Other senses (e.g., vision, touch) also play an
      important role in these environments. Third, adaptation strategies have to be
      considered when recruits or incumbents fail the screening test.

PMID- 14965452
TI  - The use of male or female voices in warnings systems: a question of acoustics.
AB  - Speech warnings and communication systems are increasingly used in noisy, high
      workload environments. An important decision in the development of such systems
      is the choice of a male or a female speaker. There is little objective evidence
      to support this decision, although there are many misconceptions and
      misunderstandings on this topic. This paper suggests that both acoustic and non
      acoustic differences (such as social attributions towards speakers of different
      sexes) between male and female speakers is negligible, therefore the choice of
      speaker should depend on the overlap of noise and speech spectra. Female voices
      do however appear to have an advantage in that they can portray a greater range
      of urgencies because of their usually higher pitch and pitch range. An experiment
      is reported showing that knowledge about the sex of a speaker has no effect on
      judgements of perceived urgency, with acoustic variables accounting for such
      differences.

PMID- 14965453
TI  - Signal perception during performance of an activity under the influence of noise.
AB  - Usually the perception of acoustic signals is investigated under conditions where
      the subjects pay full attention to the signals. It can be assumed that the
      threshold of signal perception is much higher if the attention has simultaneously
      to be focused on the execution of any kind of other activity. In the following
      experiment subjects have to perceive acoustic signals while solving different
      arithmetical tasks at the same time. The results (number of perceived signals,
      number of arithmetical tasks solved, reaction time, and solving time) show that
      the threshold of signal perception rises while other tasks are being performed
      simultaneously. Consequences for the recognition of warning signals in
      occupational safety and in traffic conditions are discussed.

PMID- 14965454
TI  - Indispensable benefits and unavoidable costs of unattended sound for cognitive
      functioning.
AB  - Critical to survival, and also to the organism's efficient management of the flow
      of information in the brain, is attentional selectivity; the ability to select
      one source of information to guide action whilst ignoring others that are
      irrelevant to the current behavioural goal. But such selectivity is not merely
      the inclusion of the relevant information and the complete neglect of irrelevant
      information. We discuss in this paper the way that all sound is processed in an
      obligatory fashion--whether relevant or irrelevant--and discuss the fate of sound
      in the case when it is irrelevant to the immediate mental task. Using the so
      called irrelevant sound paradigm we show that unattended information is both
      registered and organised. This obligatory process of organisation compromises the
      efficiency of particular types of mental activity. We discuss how such
      interference comes about but the key emphasis is upon the possible beneficial
      effects of such processing-of-the-irrelevant, in allowing the switching of
      attention to be more facile and intelligent and in allowing the accumulation of
      evidence about statistical regularities in the auditory world (such as those
      helpful to the efficient perception, acquisition and use of language). In sum, we
      describe how purposeful processing based on directed attention is in a state of
      tension with the obligatory, automatic processing of the unattended. One of the
      consequences of this tension is typically manifested in auditory distraction, but
      the benefits of processing of the attended may considerably outweigh this
      disadvantage.

PMID- 14965455
TI  - Noise and mental performance: personality attributes and noise sensitivity.
AB  - The contradictory and confusing results in noise research on humans may partly be
      due to individual differences between the subjects participating in different
      studies. This review is based on a twelve year research on the role of
      neuroticism, extroversion and subjective noise sensitivity during mental work in
      noisy environment. Neurotic persons might show enhanced "arousability" i.e. their
      arousal level increases more in stress. Additional unfavorable factors for
      neurotics are worrying and anxiety, which might prevent them coping successfully
      with noise, or some other stressors during mental performance. In numerous
      experiments introverts have showed higher sensitivity to noise during mental
      performance compared to extroverts, while extroverts often cope with a boring
      task even by requesting short periods of noise during performance. Correlation
      analyses have regularly revealed a highly significant negative relation between
      extroversion and noise annoyance during mental processing. Numerous studies have
      shown that people with high noise sensitivity may be prevented from achieving the
      same work results as other people in noisy environment, thus leading to
      psychosomatic, neurotic or other difficulties. Positive relation between noise
      annoyance and subjective noise sensitivity might be very strong. Our results have
      shown, after matching with the results of other relevant studies, that more
      stable personality, with extroversive tendencies and with a relatively lower
      subjective noise sensitivity measured with standard questionnaires, may be
      expected to better adapt to noise during mental performance, compared to people
      with opposite personality traits.

PMID- 14965456
TI  - A twin study of dietary restraint, disinhibition and hunger: an examination of
      the eating inventory (three factor eating questionnaire).
AB  - The Eating Inventory (EI) is commonly used to measure a range of eating
      behaviors. It includes three subscales: Cognitive Restraint, Hunger, and
      Disinhibition. In this study, we decomposed the variance of the three subscales,
      and evaluated the genetic, common environment and specific environmental effects
      on each in a sample of female-female twin pairs. Multivariate models were also
      used to examine whether the EI represented three individual factors, or whether
      there was extensive covariance among subscales. Heritabilities were estimated at
      45% (CI of 32-57%) for Disinhibition, 8% (CI of 0-38%) for Hunger, and 0% (CI of
      0-30%) for Restraint. Common environmental influences were estimated at 0% (CI of
      0-23%) for Disinhibition, 16% (CI of 0-34%) for Hunger, and 31% (4-42%) for
      Restraint. Specific environmental influences accounted for the rest of the
      variance of the subscales. However, multivariate modeling indicated that
      Disinhibition and Hunger covaried significantly, indicating that these two
      subscales are influenced by the same set of genetic factors. Furthermore,
      Restraint appeared to be empirically distinct from Hunger or Disinhibition.

PMID- 14965457
TI  - Diagnosing zygosity in infant twins: physical similarity, genotyping, and
      chorionicity.
AB  - We compared the results of different methods for diagnosing zygosity in a sample
      of 237 same-sex pairs of twins assessed at 5 and 18 months of age. Despite the
      twins' very young age and early stage of development, physical similarity was
      concordant with genotyping in 91.9% of cases at 5 months and 93.8% of cases at 18
      months, for a subsample of 123 and 113 pairs, respectively. This concordance rate
      was obtained following a case-by-case assessment of each pair's physical
      similarity using a shortened version of the Zygosity Questionnaire for Young
      Twins (Goldsmith, 1991). Taking into account the chorionicity data available from
      the twins' medical files, we were able to classify correctly 96% of the pairs, an
      accuracy rate comparable to previously reported rates obtained with older twins.
      Chorionicity data is especially useful since we found that monochorionic MZ twins
      are more difficult than dichorionic MZ twins to diagnose by physical similarity
      at these young ages. The relative cost-benefit of methods based on reported
      physical similarity and DNA analysis is discussed in light of these results.

PMID- 14965458
TI  - Has the "Equal Environments" assumption been tested in twin studies?
AB  - A recurring criticism of the twin method for quantifying genetic and
      environmental components of human differences is the necessity of the so-called
      "equal environments assumption" (EEA) (i.e., that monozygotic and dizygotic twins
      experience equally correlated environments). It has been proposed to test the EEA
      by stratifying twin correlations by indices of the amount of shared environment.
      However, relevant environments may also be influenced by genetic differences. We
      present a model for the role of genetic factors in niche selection by twins that
      may account for variation in indices of the shared twin environment (e.g.,
      contact between members of twin pairs). Simulations reveal that stratification of
      twin correlations by amount of contact can yield spurious evidence of large
      shared environmental effects in some strata and even give false indications of
      genotype x environment interaction. The stratification approach to testing the
      equal environments assumption may be misleading and the results of such tests may
      actually be consistent with a simpler theory of the role of genetic factors in
      niche selection.

PMID- 14965459
TI  - Genetic and environmental analysis of behavioral risk factors for adolescent drug
      use in a community twin sample.
AB  - We investigated the etiology of six problem behaviors that might facilitate an
      understanding of behavioral pathways to substance use and abuse in adolescents.
      These behavioral measures, classified as Conduct Problems, Hyperactivity, School
      Problems, Low Self-esteem, Neuroticism, and Social Withdrawal were the result of
      a previously reported (Siewert et al., 2003) modification of the Drug Use
      Screening Inventory (DUSI; Tarter, 1990; Tarter & Hegedus, 1991). We developed
      these measures as interpretable components of risk for substance use and abuse in
      a community based sample of 633 twin pairs, who were under the legal drinking age
      of 21 (mean age = 15.0 years). Using multivariate analyses, model comparisons
      indicated that these six behavioral measures could be thought of as two
      heritable, and genetically distinct, dimensions of problem behavior. Two closely
      competing models resulted from our analyses. The best fitting model hypothesized
      a general genetic factor loading on all 6 behavioral measures with a second
      genetic factor loading on only the three internalizing behavioral measures with
      loadings of 0.25-0.59 and 0.26-0.44, respectively. A second model, which fit the
      data almost as well, hypothesized one genetic factor loading only on the
      externalizing behavioral measures, and a second genetic factor loading only on
      the internalizing behavioral measures, with a correlation between the two latent
      factors of 0.75. Because our analyses show that there are two genetically
      distinct factors influencing these six problem behaviors, we anticipate that
      there may be different patterns of relationship of these factors to risk for
      substance use, abuse, and dependence.

PMID- 14965460
TI  - Between twins; research summaries; in the real world.
AB  - Research on unusually long birth intervals between twin and triplet deliveries is
      reviewed. A recent multicentre study reported gestational and survival data for
      35 multiple birth sets from 12 centers, and evaluated conservative treatment
      strategies for mothers delivering one twin fetus. Next, findings from three
      recent twin studies are reviewed: effects of close inter-twin communication on
      longevity; case report of dizygous twins with a single chorion; and a case of
      discordance for hemihypertrophy in an MZ female twin pair. The article concludes
      with summaries of three interesting and informative anecdotal accounts of twins.

PMID- 14965461
TI  - Maternal perinatal mental health and multiple births: implications for practice.
AB  - Women's mental health can be compromised during reproductive life, but to date
      there has been relatively little specific investigation of the links between
      multiple births and perinatal psychiatric illness. There has been more
      comprehensive examination of some of the psychological sequelae of multiple
      gestations and births, but many of the studies have small samples and are
      descriptive in nature. Most of the literature is drawn from investigations of the
      psychological aspects of multiple births following assisted conception. Current
      conceptualizations of the determinants of maternal perinatal mental health, with
      particular reference to multiple gestations and births are discussed and
      implications for clinical practice suggested. Overall there is evidence that
      women with multiple gestation and multiple births may be at elevated risk for
      pregnancy anxiety, postpartum depression and complicated grief reactions. Much
      less is currently known about the associations between multiple birth and either
      maternity blues or postpartum psychosis. The relationships between personal or
      family psychiatric history, past experience of childhood abuse, intimate partner
      intimidation and psychological adjustment to multiple births are not known. The
      interactions between multiple births, operative delivery, prematurity, neonatal
      illness and separation of mother and infant as contributing factors to maternal
      postpartum mental health are not known. There is very limited evidence about the
      psychological functioning of fathers of multiple infants. Routine antenatal,
      intrapartum and postnatal health care for women with multiple infants needs to
      take into account the additional psychological demands they face.

PMID- 14965462
TI  - Nutritional management of multiple pregnancies.
AB  - Good nutrition is central to achieving optimal fetal growth and development, and
      to maintaining maternal health and wellbeing. For multiple pregnancies, there is
      a growing body of evidence linking good maternal nutrition and weight gain to
      positive perinatal outcomes including reduced incidence of low birthweight and
      very low birthweight infants. Nutrition intervention appears to have important
      clinical implications for infant morbidity and mortality. Nutritional counselling
      can help women improve and maximise their intake of "at risk nutrients" such as
      iron, folate, essential fatty acids, calcium and ensure adequate energy intake to
      meet weight gain targets. Recommended optimal weight gains range from 16-20 kg
      for twin pregnancies. Expert dietetic guidance is often warranted, especially for
      women expecting triplets or quadruplets.

PMID- 14965463
TI  - Studies of twins: can they shed light on the fetal origins of adult disease
      hypothesis?
AB  - There has been much interest in evidence that people with lower birthweight have
      higher risk of adult cardiovascular disease, but the causal pathways underlying
      such observations are uncertain. Study of twins offers an opportunity to shed
      light on these pathways, in three different ways. First, in a twin pregnancy
      maternal nutritional resources and the "supply line" to the fetuses will be more
      "stretched". We hypothesise that study of twin pregnancies is a more efficient
      way to identify modifiable maternal factors that influence later health than
      studies of singleton pregnancies. Second, twins have lower birthweight than
      singletons. Comparison of cardiovascular disease risk in twins versus that in
      singletons will provide insight into whether birthweight per se is in the
      underlying causal pathway of interest, and whether factors constraining fetal
      growth of twins (versus singletons) affect later outcome. Third, twin cohorts
      provide an opportunity to investigate the role of "shared" factors versus factors
      affecting each individual fetus, by comparing results of within-cohort versus
      within-pair analyses. Generalisability of findings in twins is debated. We
      suggest that findings in monochorionic twins (or in the absence of chorionicity
      data, those from monozygotic twins) need to be interpreted with caution.

PMID- 14965464
TI  - Birthweight discordance in multiple pregnancy.
AB  - This paper reviews several aspects of discordant growth in multiple pregnancies.
      Discordant growth is not a chance event and therefore several patterns can be
      discerned. About 75% of twins exhibit < 15% discordance (concordant), 20% are 15
      25% (mildly) discordant, and about 5% are more than 25% (severely) discordant.
      Higher frequencies and increased severity are seen among triplets. Five
      observations regarding discordance became generally accepted: (a) not all
      discordant pairs are similar; (b) the larger the discordance level the greater is
      the risk for an adverse outcome; (c) discordant growth does not necessarily
      represent growth restriction; (d) a discordance level may have a different
      clinical implication in different gestational ages; and (e) the smaller fetuses
      in severely discordant pairs are at disproportionate risk for neonatal mortality.
      Mild discordance may represent a normal variation between sibs whereas severely
      discordant pairs often exhibit patterns of growth restriction. Not infrequently,
      discordance may represent an adaptation to the limited intrauterine space in
      order to increase gestational age.

PMID- 14965465
TI  - Twins and friendship.
AB  - A growing body of literature asserts the importance of friendships for a child's
      emotional wellbeing, behavioural adjustment and developmental attainment.
      However, few studies have examined friendships in the twin situation. This paper
      examines the literature on friendships among children who are twins and asks two
      questions: (1) What are the implications of the twin situation for friendship
      formation? (2) How can the twin situation inform theoretical knowledge concerning
      friendship formation in the general population? The discussion examines the
      implications of the twin situation for the size and nature of twin children's
      friendship pool and questions whether children who are twins are more likely to
      be adaptive or maladaptive in their social behaviour. The paper argues for the
      need to study the process and mechanisms in friendship formation among twin
      children because the findings might inform not only studies of friendship but
      also behavioural genetic research.

PMID- 14965466
TI  - Single embryo transfer in IVF to prevent multiple pregnancies.
AB  - As the success rates of IVF clinics improve, one of the adverse consequences is
      the increased incidence of twins, due largely to the number of embryos
      transferred. Even if the number of embryos transferred is restricted to two, the
      twinning rate can exceed 40% of the pregnancies. An obvious way to reduce this
      high twin rate would be to transfer only one embryo. This would require that
      cryopreservation of the supernumerary embryos be efficacious enough so that the
      chance of achieving an ongoing pregnancy is not diminished by transferring a
      single embryo in the stimulated cycle. Previous studies utilising embryos on day
      2 and 3 of development have shown that the pregnancy rates can be acceptable
      (about 40%) and that the cumulative rate can be up to 60%. Most of these studies,
      however, do not include a comparison with the cumulative pregnancy rate with two
      embryos transferred in the stimulated cycle. Therefore, the efficacy has not been
      proven. We present clinical data from the past few years to illustrate the
      increase in success rates and the concomitant increase in twinning rates. The
      increased success in the cryopreservation program has enabled us to trial a
      single embryo transfer program and compare the results to the transfer of two
      embryos. The results strongly suggest that the transfer of a single embryo is the
      better clinical option.

PMID- 14965467
TI  - Prevention of multiple pregnancy during ovulation induction.
AB  - Gonadotrophin ovulation induction is currently used for a heterogeneous group of
      ovulation disorders and unexplained infertility. In the United States it is
      reported that multiple pregnancy rates of greater than 30% occur as a result of
      ovulation induction, most commonly after controlled ovarian hyperstimulation and
      intrauterine insemination. Treatment strategies to reduce the incidence of
      multiple pregnancies on ovulation induction programs can be targeted to reducing
      multiple follicular development and subsequent ovulation by a more aggressive
      cancellation policy, follicle reduction by fine needle aspiration or conversion
      to IVF; or dealing with the problem of multiple gestation after it has occurred
      (i.e., multifetal pregnancy reduction). The procedures and abilities exist to
      resolve this problem. What is needed are appropriate treatment guidelines and
      well constructed trials to demonstrate that higher order multiple pregnancies can
      be substantially reduced and/or eliminated without compromising a couple's
      chances to conceive.

PMID- 14965468
TI  - T-cell receptor excision circles (TREC) in SHIV 89.6p and SIVmac251 models of HIV
      1 infection.
AB  - T-cell receptor excision circles (TREC) may be a useful surrogate marker in HIV-1
      infection for evaluating the likelihood of continued clinical stability and/or
      the response to therapeutics, including vaccines. Analysis of TREC in SHIV and
      SIV models of HIV-1 infection may provide additional information concerning the
      utility of TREC as a marker. We measured TREC in peripheral blood mononuclear
      cells (PBMC) from rhesus macaques in SHIV89.6p (n = 20) and SIVmac251 (n = 11)
      models of HIV-1 infection. TREC were also evaluated in tissues in the SIVmac251
      model at end-point. In the SHIV89.6p model, TREC in PBMC were significantly lower
      at 12 weeks postinfection compared to preinfection levels. The decrease in TREC
      correlated with the decline in CD4+ T cells (r(s) = 0.496; P = 0.026), which in
      turn correlated inversely with serum viral loads at end-point (r(s) = -0.517; P =
      0.019). Macaques that controlled SHIV89.6p infection to some degree (n = 6) had
      higher TREC at study end-point (P = 0.017). In the SIVmac251 model, TREC in PBMC
      were significantly reduced after 17 months of infection (P = 0.012) despite
      receiving highly active antiretroviral therapy (HAART) consisting of didanosine
      (ddI) and (R)-9-(2-phosphonylmethoxypropyl)-adenine (PMPA) when not cycling off
      therapy during scheduled treatment interruptions (STI). However, macaques that
      received continuous hydroxyurea (HU) in addition to the HAART regimen had higher
      end-point TREC compared to the non-HU group (P = 0.041), and the reduction in
      TREC observed at end-point within the HU group was not significant. In the
      SIVmac251 model, TREC correlated with the percentage of CD4+ T cells (r(s) =
      0.426; P = 0.048) and CD4+CD28+ T cells (r(s) = 0.624; P = 0.002), and inversely
      with CD8+ T cells (r(s) = -0.622; P = 0.002), CD8+CD28- T cells (r(s) = -0.516; P
      = 0.014), and serum viral loads (r(s) = -0.627; P = 0.039). High levels of TREC
      were observed in the thymus, levels comparable to PBMC were seen in the lymph
      node, and low but detectable levels of TREC were present in bone marrow. The use
      of correlates of TREC as covariates in ANCOVA revealed that the decline in TREC
      in the SHIV 89.6p model reflected the decline in the percentage of CD4+ T-cells
      due to viral cytopathogenicity. In the SIVmac251 model, the decline in TREC was
      related to increased immune activation and proliferation due to viral
      replication, as reflected by decreases in percentages of CD4+CD28+ T cells and
      increases in CD8+ and CD8+CD28- T cells.

PMID- 14965469
TI  - Inferred functions of "novel" genes identified in fibroblasts chondroinduced by
      demineralized bone.
AB  - Little is known about the cellular mechanisms that control postnatal chondrocyte
      differentiation. As a first step towards identifying those mechanisms, gene
      expression shifts were characterized in an in vitro model of chondroinduction. In
      previous studies, several functional classes of genes (cytoskeletal and matrix
      elements, cell adhesion proteins, peptide growth factors, and signal transduction
      proteins) were found to be altered in human dermal fibroblasts (hDFs) cultured in
      porous collagen sponges with chondroinductive demineralized bone powder (DBP) for
      3 days. In addition, a number of "novel" sequences were identified. In this
      study, molecular techniques were combined with computational methods to
      characterize those sequences. Gene expression of all 10 novel sequences tested
      was found in hDFs by RT-PCR. The sequences were compared to the human genome, and
      their cellular functions were inferred from genes that mapped to the same
      chromosomal coordinates. Only one of the novel sequences contained a protein
      coding region (kinesin superfamily protein 26B). The others contained 3'
      untranslated (osteonectin, alpha-V integrin, RAP2B) or other untranslated regions
      (PTPN21, GAS6) of mRNAs. The cellular functions of the DBP-regulated genes
      described in this study fall into similar categories as those previously
      identified. These results provide new details on the cellular response of hDFs
      exposed to DBP.

PMID- 14965470
TI  - Transcriptional activation by the zinc-finger homeodomain protein delta EF1 in
      estrogen signaling cascades.
AB  - The transcription factor delta EF1 is a key player in estrogen-signaling cascades
      in vertebrates. In this pathway, estrogen induces the expression of the gene
      encoding delta EF1, and then delta EF1 activates transcription of downstream
      targets. Yet, the molecular mechanisms of transcriptional activation by delta EF1
      have remained obscure. Furthermore, most work has concentrated on the capacity of
      delta EF1 to repress gene expression, rather than its ability to activate
      transcription. To investigate this activation potential in an endogenous
      signaling pathway, we characterized ovalbumin (Ov) gene induction by delta EF1.
      Gel mobility shift assays demonstrate that delta EF1 binds to the 5' flanking
      region of the Ov gene at two sites, one at -810 to -806 and one at -152 to -148
      with respect to the start point of transcription. Correspondingly, these sites
      are required for induction by estrogen or by delta EF1 in transfection
      experiments. Furthermore, the activation potential of delta EF1 is not restricted
      to the chick homolog, as the human ZEB and the mouse delta EF1 homologs also
      induce Ov gene expression. To characterize the molecular mechanisms whereby delta
      EF1 activates gene expression, its C-terminal acidic domain was deleted and shown
      to be necessary for activation of transcription. Furthermore, the acidic domain
      has intrinsic activation potential, as it can induce the heterologous thymidine
      kinase promoter. These data establish delta EF1 as an activator of transcription
      whose action may be DNA-context and cell-type specific, but not species specific.

PMID- 14965471
TI  - Expression of protooncogene c-kit receptor in rat testis and uniqueness of
      extracellular domain across the species with potential in molecular phylogeny.
AB  - We studied expression of protooncogene c-kit receptor in Brown Norway rat Rattus
      norvegicus testis during different stages of postnatal development. Several
      regions from within the c-kit gene encompassing different domains were amplified
      employing reverse transcriptase polymerase chain reaction, and the resultant
      amplicons were cloned and characterized. Maximum expression of c-kit was observed
      in the testes during the days 10 to 30, suggesting its involvement in transition
      of primary spermatocytes towards formation of mature spermatozoa. Multiple novel
      transcripts originating from the extracellular domain were also identified,
      though their functions remained unknown. The evolutionary divergence of c-kit
      cDNA of 10 other vertebrates was studied using their sequences from the GenBank.
      Analyses of c-kit cDNA and its protein sequences in rat and related genomes
      showed organizational uniqueness across the species. Construction of phylogenetic
      tree, based on c-kit cDNA and protein sequences delineated all the species
      successfully and was found to be in accordance with the established positioning
      of these animals. The organizational uniqueness of c-kit cDNA sequences from the
      extracellular domain may be exploited as a useful tool in delineating
      phylogenetic relationship of different species.

PMID- 14965472
TI  - Comparative analysis of two slc11 (Nramp) loci in Takifugu rubripes.
AB  - To study the evolution of the solute carrier family 11 (slc11; formerly Nramp)
      protein, we isolated and characterized two paralogs from the pufferfish Takifugu
      rubripes (Fugu). These teleost genes, designated Fugu slc11a-a and Fugu slc11a-b,
      comprise open reading frames of 1743 nucleotides (581 amino acids) and 1662 nt
      (554 aa), respectively. The proteins are 81% similar, and both exhibit signature
      features of the slc11 family of proteins including 12 transmembrane domains, a
      conserved transport motif and a glycosylated loop. Both Fugu paralogs are more
      Slc11a2-like based on sequence homology and phylogenetic studies. Analysis of
      gene environment placed both in the proximity of multiple loci syntenic to human
      chromosome 12q13, that is, within a SLC11A2 gene environment. However, Fugu
      slc11a-a also gave one match with chromosome 2q35, where human SLC11A1 resides.
      Functional diversification was suggested by differences in tissue distribution
      and subcellular localization. Fugu slc11a-a exhibits a restricted expression
      profile and a complex subcellular localization, including LAMP1 positive late
      endosomes/lysosomes in transiently transfected mouse macrophages. Fugu slc11a-b
      is expressed ubiquitously and localizes solely to late endosomes/lysosomes. This
      comparative analysis extends our understanding of the evolution and function of
      this important family of divalent cation transporters. [Sequence data from this
      article have been deposited with the EMBL/GenBank Data Libraries under accession
      nos. AJ496547/8/9 and AJ496550.]

PMID- 14965473
TI  - Elucidation of the interactions between C99, presenilin, and nicastrin by the
      split-ubiquitin assay.
AB  - The interactions between C99, presenilin, and nicastrin were investigated by a
      split-ubiquitin assay. We found that C99 homodimerizes and binds weakly to
      presenilin and strongly to nicastrin. Domain mapping assays revealed the
      transmembrane and cytoplasmic carboxy-terminal region of C99 is sufficient for
      the dimerization of C99 and the interaction between C99 and nicastrin. The
      extracellular domain of C99 is responsible for binding to presenilin. Nicastrin
      bound to C99 via its transmembrane domain and carboxy-terminal region. These
      observations suggest that dimerized (or oligomerized) C99 directly interacts with
      presenilin, and that this interaction is facilitated by nicastrin.

PMID- 14965474
TI  - TIAF1 and p53 functionally interact in mediating apoptosis and silencing of TIAF1
      abolishes nuclear translocation of serine 15-phosphorylated p53.
AB  - TIAF1 is a TGF-beta 1-induced factor that protects L929 fibroblasts from TNF
      mediated apoptosis. In contrast, overexpressed TIAF1 induces growth inhibition
      and apoptosis of monocytic U937 and various nonfibroblast cells. TIAF1-mediated
      apoptosis of U937 cells involves upregulation of p53, p21, and Smad2/4, but
      downregulation of ERK phosphorylation. To determine whether p53 and TIAF1
      functionally interact in regulating cell death, ectopic TIAF1 and p53 were shown
      to induce apoptosis of U937 cells in both synergistic and antagonistic manners.
      At optimal levels both TIAF1 and p53 mediated apoptosis cooperatively. Also, both
      proteins suppressed adherence-independent growth of L929 cells. In contrast,
      initiation of apoptosis by overexpressed TIAF1 was blocked by low doses of p53,
      and vice versa. Furthermore, ectopic p53 blocked an ongoing apoptosis in U937
      cells stably expressing TIAF1. Yeast two-hybrid analyses failed to demonstrate
      the binding of p53 with TIAF1, suggesting an unidentified protein that links the
      p53/TIFA1 interaction. Suppression of TIAF1 expression by siRNA could not inhibit
      Ser15 phosphorylation in p53 in response to UV and etoposide. However, nuclear
      translocation of these Ser15-phosphorylated p53 was significantly reduced in
      TIAF1-silenced cells. Taken together, TIAF1 and p53 functionally interact in
      regulating apoptosis, and TIAF1 is likely to participate in the nuclear
      translocation of activated p53.

PMID- 14965475
TI  - Challenges in surgical therapy evaluation.

PMID- 14965476
TI  - Continence pessaries in the management of urinary incontinence in women.
AB  - OBJECTIVE: To evaluate the effectiveness of continence pessaries for the
      management of urinary incontinence in women. METHODS: A retrospective review of
      the records of 100 women who chose to try a pessary to treat their urinary
      incontinence. Demographic data, presenting symptoms, physical findings, results
      of objective testing (pad tests and urodynamics), and incontinence outcomes were
      abstracted. Factors such as age, pelvic prolapse, presenting symptoms, pessary
      type, and history of previous incontinence surgery were examined using the
      Student t-test, chi-square test, or Fisher exact test where appropriate. RESULTS:
      The mean age of the women was 56 years (range, 28-86 years) and mean parity was
      2.5 (range, 0-13). Presenting complaints included stress incontinence in 41
      women, mixed incontinence in 53 women, urge incontinence in 3 women, and combined
      prolapse and incontinence in 3 women. All 100 women returned for follow-up
      visits. Forty women had their pessary size or type adjusted at the first follow
      up visit. At a mean follow-up time of 11 months (range, 2-42 months), 59 women
      continued to experience a complete resolution or decrease in their incontinence
      and chose to continue use of a pessary. Age, presenting symptoms, degree of
      pelvic prolapse, and type of pessary did not affect the success of pessary
      treatment. Women who had undergone incontinence surgery prior to pessary fitting
      had a higher failure rate, with relative risk (RR) of 1.6. CONCLUSION: Urinary
      incontinence pessaries are effective. More than 50% of women who try a continence
      pessary will continue to use it to manage their urinary incontinence.

PMID- 14965477
TI  - Maternal and perinatal outcomes of eclampsia: Nova Scotia, 1981-2000.
AB  - OBJECTIVE: To determine the prevalence of eclampsia and the associated maternal
      and perinatal outcomes in the province of Nova Scotia. METHODS: From the Nova
      Scotia Atlee Perinatal Database, the population-based rates of preeclampsia,
      eclampsia, and HELLP (hemolysis, elevated liver enzymes, low platelet count)
      syndrome for the period 1988 to 2000 were determined. A retrospective case review
      was then performed of all women with eclampsia at the tertiary maternity hospital
      in Halifax, Nova Scotia, Women's Hospital, IWK Health Centre, for the years 1981
      to 2000. RESULTS: In the province of Nova Scotia from 1988 to 2000, there were
      142,362 births. Thirty-nine women developed eclampsia (0.27/1000). Over this time
      interval, the prevalence of severe preeclampsia fell from 2.08% to 1.63%, and the
      diagnosis of HELLP syndrome increased from 0.03% to 0.31%. At the Women's
      Hospital, IWK Health Centre, between 1981 and 2000, there were 31 cases of
      eclampsia in 105,651 deliveries (0.29/1000). Sixty-one percent of first
      convulsions occurred antepartum, 13% occurred intrapartum, and 26% occurred
      postpartum. Eighty-one percent of women reported prodromal symptoms. Sixty-one
      percent of the women received anti-hypertensive therapies, 48% received
      antiepileptic therapies, and 97% received magnesium sulfate. Ten percent of the
      women had convulsions while on magnesium sulfate therapy. Antepartum eclampsia
      was associated with increased rates of general anaesthesia (26%) and Caesarean
      section (79%). There were no maternal deaths, but the rate of major maternal
      complications was 32%. The perinatal mortality rate was 64 in 1000 deliveries,
      and the rate of severe perinatal complications was 56%. CONCLUSION: The incidence
      of eclampsia in Nova Scotia is 0.27 per 1000 deliveries. Although rare, this
      condition is associated with significant maternal and perinatal morbidity.

PMID- 14965478
TI  - Factors affecting academic promotion in obstetrics and gynaecology in Canada.
AB  - OBJECTIVE: (1) To determine if women faculty members in departments of Obstetrics
      and Gynaecology were less likely than men to achieve promotion; and (2) to assess
      gender differences in attitudes towards promotion. METHODS: Department chairs at
      the 16 medical schools in Canada were approached to participate in this study. A
      questionnaire was mailed to the obstetricians/gynaecologists in faculties of
      medicine at the 15 Canadian medical schools that agreed to participate.
      Likelihood of promotion for women and men was compared using survival analysis,
      controlling for other factors. Survival (event) time was the time in years
      between completion of residency and achieving promotion. RESULTS: The response
      rate was 72% (376/522). Overall, 37% of respondents were women, and 63% were men.
      The women respondents were younger than the men, with a mean age of 43.4 +/- 7.9
      years compared to 52.8 +/- 8.9 years. Of those in an academic stream, 39% of
      women (29/75) and 62% of men (90/145) had attained senior academic ranks.
      Completing residency more recently was associated with a higher likelihood of
      promotion to Assistant Professor (hazard ratio [HR], 1.05; P <0.001). The
      likelihood of promotion to Professor was lower for women than for men (HR, 0.40;
      P = 0.05). Having a mentor was associated with a higher likelihood of promotion
      to Professor (HR, 2.33; P = 0.002). Women were more likely to perceive barriers
      to promotion, such as family care responsibilities (P <0.001). CONCLUSION:
      Independent of the respondent's gender, recent completion of residency and having
      a mentor were the most significant factors increasing the likelihood of promotion
      in Canadian medical school departments of Obstetrics and Gynaecology. As women
      were found to be less likely than men to achieve promotion to Professor,
      mentoring and strategies that focus on facilitating promotion for women should be
      encouraged to ensure there are academic leaders in obstetrics and gynaecology in
      the future.

PMID- 14965479
TI  - Ovarian teratoma diagnosis and management: case presentations.
AB  - BACKGROUND: Ovarian teratomas (OTs) may be of mature or immature morphologies.
      Mature cystic teratomas (MCTs), often referred to as dermoid cysts, are the most
      common germ cell tumours of the ovary in women of reproductive age. OTs are
      usually asymptomatic until they reach considerable size. Frequently,
      ultrasonography is diagnostic. Women requiring surgery for OTs should be
      appropriately counselled about the risks and benefits of laparoscopic and open
      approaches. CASE PRESENTATIONS: Case I: An 18-year-old woman presented with
      hirsutism and irregular menses, both of which reversed after bilateral MCT
      removal by laparoscopy. Case II: A 47-year-old multigravid woman presented with a
      large unilateral OT, with a focus of malignancy. Case III: A 19-year-old woman
      presented with a large unilateral OT associated with gliomatosis peritonei.
      CONCLUSION: Experienced laparoscopic surgeons should consider laparoscopy as an
      alternative to laparotomy in management of OT in selected cases. Women younger
      than 15 years of age or older than 45 years of age who have large, solid
      teratomas on ultrasound or positive markers for germ cell tumours are at risk for
      malignant variants, and for these women laparotomy is the preferred approach.

PMID- 14965480
TI  - Canadian contraception consensus.
AB  - OBJECTIVE: To provide guidelines for health-care providers on the use of
      contraceptive methods to prevent pregnancy and sexually transmitted diseases.
      OUTCOMES: Overall efficacy of cited contraceptive methods, assessing reduction in
      pregnancy rate, risk of infection, safety, ease of use, and side effects; the
      effect of cited contraceptive methods on sexual health and general well-being;
      and the cost and availability of cited contraceptive methods in Canada. EVIDENCE:
      Medline and the Cochrane Database were searched for articles in English on
      subjects related to contraception, sexuality, and sexual health from January 1988
      to March 2003, in order to update the Report of the Consensus Committee on
      Contraception published in May-July 1998. Relevant Canadian Government
      publications and position papers from appropriate health and family planning
      organizations were also reviewed. VALUES: The quality of the evidence is rated
      using the criteria described in the Report of the Canadian Task Force on the
      Periodic Health Examination. Recommendations for practice are ranked according to
      the method described in this Report.

PMID- 14965481
TI  - Do we need a better test? Can thrombin generation be useful?

PMID- 14965482
TI  - Erythropoietin to treat head and neck cancer patients with anemia undergoing
      radiotherapy.

PMID- 14965483
TI  - Update on the clinical spectrum and genetics of red blood cell membrane
      disorders.
AB  - Disorders of the red blood cell membrane, such as hereditary spherocytosis,
      hereditary elliptocytosis, and hereditary pyropoikilocytosis, are characterized
      by heterogeneity in their clinical and laboratory manifestations. Advances in
      molecular biology have allowed determination of the precise genetic defect in
      many cases of membrane-associated anemia and have revealed significant genetic
      heterogeneity. Six genetic loci have been identified and many defects, including
      gene deletions and insertions, missense and nonsense mutations, and splicing
      mutations, have been found. Analysis of these defects has provided a better
      understanding of the pathogenesis of these disorders and allowed a better
      understanding of the structure/function relationships of the proteins of the
      erythrocyte membrane.

PMID- 14965484
TI  - Overcoming blood shortages: red blood cell and platelet substitutes and membrane
      modifications.
AB  - Blood shortages are increasingly common as the donor base declines and extensive
      restrictions on blood donation disqualify many donors. Red blood cell (RBC) and
      platelet substitutes have long been anticipated as alternatives to standard
      transfusions. However, difficulties in manufacturing, efficacy, and safety have
      slowed the development of these products. New understanding of the relationship
      between blood viscosity, oxygen transport, and vasoactivity have led to more
      effective RBC substitutes, several of which are in advanced clinical trials. In
      addition, creative approaches to RBC membrane modification, such as the enzymatic
      cleavage of ABH glycoproteins, may lead to a universal RBC. Advances in the
      understanding of platelet membrane behavior at low temperatures may lead to
      extended platelet storage at refrigerator temperatures. Standard transfusions of
      human RBCs and platelets will not be replaced soon. However, these new products
      will be a useful alternative for selected clinical applications and will lessen
      our dependence on our marginally adequate blood supply.

PMID- 14965485
TI  - The anemia of malaria infection: role of inflammatory cytokines.
AB  - Death from malaria occurs from the complications of the infection: cerebral
      manifestations leading to coma and a severe and refractory anemia leading to
      hypoxia and cardiac decompensation. Several mechanisms have been identified to
      play a role in the pathogenesis of malarial anemia, such as erythrocyte lysis and
      phagocytosis, and sequestration of parasitized red blood cells, but recent data
      indicate that these mechanisms (singly or in combination) do not adequately
      explain the severity of this anemia. By contrast, hematologic studies have shown
      that bone marrow suppression and ineffective erythropoiesis contribute
      importantly to the severe anemia of malaria infection. The host mechanisms
      responsible for suppression of erythropoiesis may involve an excessive or
      sustained innate immune response or a pathologic skewing of the T-cell
      differentiation response with the attendant production of certain proinflammatory
      cytokines. Experimental data also indicate that severe malarial anemia is
      associated with the immunologic expression of a circulating inhibitor of
      erythropoiesis that functionally antagonizes the action of erythropoietin. We
      review the clinical and experimental basis for these concepts and discuss ongoing
      experimental and genetic studies aimed at unraveling the molecular basis of this
      malaria-induced bone marrow suppression.

PMID- 14965487
TI  - Intravenous anti-D to avoid splenectomy in adult immune thrombocytopenic purpura.

PMID- 14965488
TI  - Improving platelet safety: bacterial contamination of platelets.
AB  - In developed countries, transfusion-transmitted bacterial contamination of
      platelets is the most common cause of fatalities related to transfusion
      transmitted disease. Platelets, to maintain viability and function, must be
      stored at room temperature (20 degrees-24 degrees C), which creates an excellent
      growth environment for the proliferation of bacteria. Multiple studies have shown
      that 1:1000 to 1:2000 platelet units are bacterially contaminated. It is
      estimated that the risk of a bacterial-related death after a transfusion of a
      platelet unit ranges from 1:7500 to 1:100,000. The use of bacterial detection to
      minimize the risk of transfusion-related bacterial sepsis is gaining favor around
      the world. Implementation of bacterial detection methods would improve safety for
      patients, result in an extension of the shelf life of platelets, and reduce the
      outdating of platelets, thus being a cost-saving safety intervention.

PMID- 14965486
TI  - The clinical relevance of new insights in iron transport and metabolism.
AB  - There have been major basic advances in the field of iron metabolism in recent
      years. These advances include the discoveries of the HFE-1 gene, a series of
      transmembrane iron transporters or cotransporters (eg, divalent metal transporter
      1, duodenal cytochrome b, ferroportin-1, hephaestin, and transferrin receptor-2),
      and two key regulatory proteins named hepcidin and hemojuvelin. Several mutations
      of these various proteins have been linked to human diseases. These discoveries
      have led to major improvements in our understanding of iron physiology and have
      also profoundly modified and extended the pathologic iron field. Clinical
      applications have rapidly emerged with the appearance of new iron overload
      syndromes and the practical input of new genetic tools enabling the noninvasive
      diagnosis of HFE-1 hemochromatosis. These basic advances are paving the road for
      innovative therapeutic strategies not only in iron overload syndromes but also in
      the wide area of chronic disease-related anemia.

PMID- 14965489
TI  - Thrombocytopenia in pregnancy.
AB  - Thrombocytopenia, classically defined as a platelet count of lower than
      150,000/mL, has been observed in 7% to 10% of unselected pregnancies in the past
      20 years because platelet counts are included with automated blood cell counters
      in routine prenatal screenings. Severe thrombocytopenia with a platelet count of
      lower than 50 x 10(9)/L is rare, occurring in less than 0.1% of pregnancies.

PMID- 14965490
TI  - Thrombocytopenia in the newborn.
AB  - Thrombocytopenia is the most common hemostatic abnormality in sick newborn
      infants. Although many conditions may be associated with neonatal
      thrombocytopenia, low platelet counts in the first few days of life are often
      caused by fetomaternal problems, whereas thrombocytopenia developing after the
      third day is usually secondary to sepsis or necrotizing enterocolitis. Despite
      the frequency of thrombocytopenia in sick neonates, the underlying kinetic
      mechanisms are not always clear. The commonly accepted theories of decreased
      platelet production or increased consumption are being scrutinized in the light
      of new evidence. Thrombopoietin and interleukin-11 are being investigated to
      unravel the complex pathophysiology of thrombocytopenia in neonates and they are
      also being explored as potential therapeutic agents. Guidelines for platelet
      transfusions continue to be variable and controversial.

PMID- 14965491
TI  - Thrombocytopenia after treatment with platelet glycoprotein IIb/IIIa inhibitors.
AB  - Abciximab, eptifibatide, and tirofiban are the three drugs approved by the US
      Food and Drug Administration designed to block platelet aggregation by binding
      glycoprotein IIb/IIIa. Results from large therapeutic trials demonstrate that all
      three agents induce thrombocytopenia in approximately 1% to 5% of cardiac
      patients. Thrombocytopenia is typically rapid in onset and antibody mediated. In
      vitro evidence suggests abciximab-induced thrombocytopenia is associated with
      antibodies directed to murine sequences within the chimeric anti-IIb/IIIa
      molecule. In addition, abciximab, eptifibatide, and tirofiban also function as
      mixed agonist-antagonists in vivo, inducing neoepitopes within the glycoprotein
      IIb/IIIa receptor that may react with pre-existing or induced antibodies.
      Screening for the development of these antibodies may reduce the incidence of
      thrombocytopenia associated with these agents, but it may limit their chronic
      usage.

PMID- 14965538
TI  - Issues in plasticity and development: Language in atypical children.

PMID- 14965539
TI  - Language development in children at risk for language impairment: cross
      population comparisons.
AB  - At 3 years of age the spontaneous language of 17 typically developing children
      was compared to two groups of toddlers who were at risk for language delay for
      very different reasons. One at-risk group, late talkers, appeared normal in all
      respects except for their delayed language. These 20 children scored at or below
      the fifteenth percentile for expressive vocabulary on the MacArthur Communicative
      Development Inventory (Fenson et al., 1993) when originally identified at 20-27
      months of age and within the normal range on the Bayley Scales of Infant
      Development (Bayley, 1969). The other group, 21 children with unilateral focal
      brain injury, suffered localized damage to their brain prenatally, perinatally,
      or within the first 6 months of life. Results indicated that both of the at-risk
      groups were still significantly lower in vocabulary diversity and grammar at 3
      years of age. There was also significantly greater variability in the at-risk
      groups than in the control groups, and in the children with focal brain injury
      than in the late talkers in both areas. The importance of language comprehension
      to development in this period was supported by two findings. First, children with
      focal brain injury had significantly lower scores than late talkers on the Index
      of Productive Syntax, a test of emerging grammar, and had been lower in
      comprehension on a standardized test of language comprehension a year earlier.
      Second, late talkers with delay in comprehension as well as production had
      significantly lower scores on IPSyn than those with normal comprehension,
      suggesting that they are at greater risk for continued delay. Qualitative
      analyses indicated that the at-risk groups produced the same kinds of errors, but
      that late talkers produced a substantially greater proportion of errors in
      obligatory contexts than did children with focal brain injury.

PMID- 14965540
TI  - Mechanisms of verbal memory impairment in four neurodevelopmental disorders.
AB  - Profiles of verbal learning and memory performance were compared for typically
      developing children and for four developmental disorders characterized by
      different patterns of language functioning: specific language impairment, early
      focal brain damage, Williams Syndrome, and Down Syndrome. A list-learning task
      was used that allowed a detailed examination of the process of verbal learning,
      recall, and recognition (California Verbal Learning Test--Children's Version).
      Distinct patterns of performance characterized the four disorders. These patterns
      were consistent with the language deficits typically seen in the disorders, with
      the exception of a dissociation seen in Williams Syndrome.

PMID- 14965541
TI  - The development of morphosyntactic ability in atypical populations: The
      acquisition of tag questions in children with early focal lesions and children
      with specific-language impairment.
AB  - We examined the development of some features of morphosyntactic ability,
      specifically the acquisition of auxiliaries and use of agreement marking, along
      with sentence processing capacity. We used a conceptually simple task called the
      Tags Question Task, which is a method for evaluating a number of language
      processes in the production of a commonly used, familiar linguistic device. We
      compared the performance of children with early focal lesions (N=21), children
      with specific-language impairment (N=24), and typically developing children
      (N=24) matched in age and nonverbal ability; additional analyses involved
      comparisons of children matched on performance level. The data converge to
      support a "delayed" development of language behavior in our clinical groups, as
      overall patterns of performance and age-related changes on individual tag
      features and tag questions were strikingly similar in all three groups across a
      number of methods of comparison. Implications for theories of the development of
      brain-language relationships as they pertain to early focal brain damage,
      specific-language impairment, and the language acquisition process in typically
      developing children are discussed.

PMID- 14965542
TI  - Productive use of the English past tense in children with focal brain injury and
      specific language impairment.
AB  - In this study, 22 children with early left hemisphere (LHD) or right hemisphere
      (RHD) focal brain lesions (FL, n=14 LHD, n=8 RHD) were administered an English
      past tense elicitation test (M=6.5 years). Proportion correct and frequency of
      over-regularization and zero-marking errors were compared to age-matched samples
      of children with specific language impairment (SLI, n=27) and with typical
      language development (TD, n=27). Similar rates of correct production and error
      patterns were observed for the children with TD and FL; whereas, children with
      SLI produced more zero-marking errors than either their FL or TD peers.
      Performance was predicted by vocabulary level (PPVT-R) for children in all
      groups, and errors did not differ as a function of lesion side (LHD vs. RHD).
      Findings are discussed in terms of the nature of brain-language relations and how
      those relationships develop over the course of language learning.

PMID- 14965543
TI  - Grammaticality sensitivity in children with early focal brain injury and children
      with specific language impairment.
AB  - Grammaticality judgments and processing times associated with violation detection
      were examined in typically developing children, children with focal brain lesions
      (FL) acquired early in life, and children with specific language impairment
      (SLI). Grammatical sensitivity in the FL group, while below typically developing
      children, was above levels seen in children with SLI. Age effects were noted with
      developmental changes in sensitivity extending into adolescence. Developmental
      delays in grammatical processing were particularly pronounced for children with
      SLI, who showed sensitivity levels below those of younger typically developing
      children. Sensitivity to agreement violations was also protracted in the SLI
      group providing further evidence of the vulnerability of morphology, a pattern
      not unlike that seen in adult aphasics. Findings for the FL group provide
      compelling evidence of neural and behavioral plasticity in children with early
      unilateral brain injury. Moreover, results from these children underscore how
      very different compensatory organization may be compared to profiles seen in
      adult aphasics who have comparable lesions. In contrast, although it was expected
      that the SLI children would perform below the typically developing children, the
      disadvantage seen with respect to the FL group suggests that the underlying
      pathology responsible for SLI may be more pervasive and less plastic than the
      focal pathology of children with early brain damage.

PMID- 14965544
TI  - "Frog, where are you?" Narratives in children with specific language impairment,
      early focal brain injury, and Williams syndrome.
AB  - In this cross-population study, we use narratives as a context to investigate
      language development in children from 4 to 12 years of age from three
      experimental groups: children with early unilateral focal brain damage (FL;
      N=52); children with specific language impairment (SLI; N=44); children with
      Williams syndrome (WMS; N=36), and typically developing controls. We compare the
      developmental trajectories of these groups in the following domains:
      morphological errors, use of complex syntax, complexity of narrative structure,
      and types and frequency of evaluative devices. For the children with early
      unilateral brain damage, there is initial delay. However, by age 10, they are
      generally within the normal range of performance for all narrative measures.
      Interestingly, there are few, if any, side specific differences. Children with
      SLI, who have no frank neurological damage and show no cognitive impairment
      demonstrate significantly more delay on all morphosyntactic measures than the FL
      group. Quantitatively, on morphosyntactic measures, the SLI group clusters with
      those children with WMS who are moderately retarded. Together these data help us
      to understand the extent and nature of brain plasticity for language development
      and those aspects of language and discourse that are dissociable.

PMID- 14965545
TI  - Explaining and interpreting deficits in language development across clinical
      groups: where do we go from here?

PMID- 14965546
TI  - Plasticity and development.

PMID- 14965547
TI  - A study of air pollutants and acute asthma exacerbations in urban areas: status
      report.

PMID- 14965549
TI  - Preoperative hormone therapy trials for breast cancer.
AB  - Preoperative hormone therapy for breast cancer has the potential to downstage a
      primary tumour hence increasing operability as well as making breast conservation
      feasible. Whether it will achieve any clinically significant survival benefit
      remains to be elucidated. Preoperative hormone therapy, in contrast to
      neoadjuvant chemotherapy, produces less severe side effects and can be continued
      throughout the perioperative period. Presurgical studies have demonstrated anti
      tumour effects of hormone therapy, e.g. down-regulation of ER. Current clinical
      trials have shown that, in patients with ER positive tumours, a response
      approaching 70% is reached in approximately three months using the traditional
      hormonal agent tamoxifen. The tumour seldom progresses during this period. New
      agents (such as third generation aromatase inhibitors and pure anti-oestrogens)
      may produce more profound and rapid responses. Future trials are required to
      identify factors other than ER to precisely predict response so that appropriate
      patients can be selected. The best agents, the ideal methods of monitoring
      response and the optimum duration of therapy also need to be identified. Clinical
      trials also need to test if pre- and perioperative hormone therapy is superior to
      conventional adjuvant hormone therapy in patients with early breast cancer.

PMID- 14965550
TI  - Nationwide breast cancer screening programme fully implemented in The
      Netherlands.
AB  - The period 1990-1997 saw the implementation of a nationwide breast cancer
      screening programme in the Netherlands, which provided biennial mammography for
      all women aged 50-69 years (50-75 years at present). The National Evaluation Team
      monitors the programme annually collecting regional data on screening outcomes;
      regional cancer registries provide data on interval cancers and on breast cancers
      in unscreened women by linkage of cancer registry data to data on screened women.
      Of 4 million women invited, 78.5% attended for screening. Screening resulted in
      13.1 referrals, 9.2 biopsies and 6.1 breast cancers detected per 1000 women
      screened initially (6.9, 4.5 and 3.5 per 1000 in subsequently screened women,
      respectively). Within the first 2 years following screening 0.95 interval cancers
      per 1000 women-years were diagnosed. The stage distribution of screen-detected
      cancers was more favourable than that of interval cancers and of those diagnosed
      in unscreened women. The results are largely consistent with expectations.
      Results may nonetheless be further improved, particularly the detection rate in
      subsequent screens.

PMID- 14965551
TI  - Breast cancer screening programme in The Netherlands: an interim review.
AB  - The year 1988 saw the introduction of a nationwide breast cancer screening
      programme in the Netherlands. Some 10 years on, a network that extended
      throughout the country was in place and all women in the target group had been
      invited to undergo screening at least once. Of the original target group, which
      was made up of women aged 50-70, around 80% responded to this invitation, an
      indication of their trust. Is that trust justified? and do the results justify
      the enormous effort of all those who make the screening programme possible, the
      cooperation of the nearly 4 million women who by now have taken part and the 17
      million pound sterling that are currently needed per year to fund the programme?
      The time has come to assess and review. The ultimate test is obviously whether
      women participating in the screening programme have a lower chance of dying of
      breast cancer than women not participating in the programme. Yet, as the breast
      cancer screening programme is one of the best documented facilities in the Dutch
      health care system, a reliable mid-term review can be made. The article by
      Fracheboud that appears in this issue provides a number of important results.
      Important elements of this programme are considered in this review.

PMID- 14965552
TI  - Applied kinesiology for treatment of women with mastalgia.
AB  - To determine whether an applied kinesiology technique was of benefit to women
      with breast pain, an open pilot study was conducted in which 88 newly presenting
      women with self-rated moderate or severe mastalgia were treated by applied
      kinesiology. This involved a hands-on technique consisting of rubbing a series of
      'lymphatic reflex points' while touching painful areas of the breasts. The women
      were predominantly pre-menopausal, and patients with both cyclical and non
      cyclical pain were included in the study. Patients' self-rated pain scores, both
      before and immediately after applied kinesiology were compared, together with a
      further score 2 months later. Immediately after treatment there was considerable
      reduction in breast pain in 60% of patients with complete resolution in 18%. At
      the visit after 2 months, there was a reduction in severity, duration and
      frequency of pain of 50% or more in about 60% of cases (P<0.0001). This
      preliminary study suggests that applied kinesiology may be an effective treatment
      for mastalgia, without side-effects and merits testing against standard drug
      therapies.

PMID- 14965553
TI  - Screening for breast cancer is associated with a low degree of psychological
      distress.
AB  - Psychological distress was measured among women on the day of recall after
      mammography in an official screening programme, and 4 weeks after the diagnosis
      was given. The Hospital Anxiety and Depression Scale (HADS) and a questionnaire
      to assess reactions to the examination were completed by 213 (97%) women aged 50
      69 years. Among those without cancer, there were 45 (24.3%) who were anxiety
      cases and eight (4.3%) depression cases (HADS) on the day of recall mammography
      and 12 (7.3%) and three (1.8%) respectively after 4 weeks (P<0.001). Among those
      with cancer, the corresponding figures were seven (28.0%) and one (4.8%) before
      and six (24.0%) and three (12%) after screening (n.s.). A total of 194 (97%)
      women were definitely satisfied with the screening programme, and 195 (98%) would
      recommend others to participate. In conclusion, recall after mammography is
      associated with transiently increased levels of anxiety and depression in women
      without cancer. For those with cancer, the psychological distress continues. The
      women were almost unanimously content with participating in the screening
      programme.

PMID- 14965554
TI  - Oestrogen receptor status determines oncological benefits of laparoscopic
      oophorectomy.
AB  - A meta-analysis of over 3000 patients in 1992 demonstrated that ovarian ablation
      in women less than 50 years of age produces a highly significant reduction in
      both disease recurrence and mortality. Laparoscopic ovarian ablation has been
      offered to premenopausal women at the University College Hospital in Galway for
      12 years. A review of 136 cases with follow-up and examination of disease-free
      survival and mortality is presented. The influence of oestrogen receptor status
      on response and long-term outcome is examined. Premenopausal women over the age
      of 40 years were offered bilateral laparoscopic oophorectomy. This procedure was
      well tolerated with no serious morbidity. A significant difference in disease
      free survival and reduction in mortality was observed in the oestrogen receptor
      positive group when compared with women with oestrogen receptor negative disease.
      No significant difference in disease-free survival or mortality was observed
      between the oestrogen receptor negative group and a comparable control group.
      These results have influenced our patient selection for this adjuvant treatment.
      A controlled prospective trial is now necessary to examine the role of
      laparoscopic oophorectomy in oestrogen receptor negative, premenopausal women
      with breast cancer.

PMID- 14965555
TI  - Wire-guided excision of non-palpable breast cancer: determinants and correlations
      between radiologic and histologic margins and residual disease in re-excisions.
AB  - In cases of wire-guided excision of non-palpable breast cancer (WGE), data
      concerning the determinants and correlations between radiologic and histologic
      margins and residual cancer in re-excisions are sparse. A total of 21 variables
      in 66 WGE followed by 49 re-excisions were prospectively analyzed. In
      multivariate analysis, only large mammographic lesions were clearly related to
      positive margins in specimen radiography (P<0.05). Multifocality (P<0.001), large
      pathologic size (P<0.05) and superficial excision (P<0.05) were related to
      positive histologic margins and multifocality (P=0.001) to residual disease in re
      excisions. The sensitivity, specificity and positive predictive values of
      specimen radiography for predicting histologic margins were 33%, 79% and 53%, and
      those for predicting residual disease 30%, 80% and 38%, respectively. The ability
      of histologic margins to predict residual disease was 91%, 58% and 38%,
      respectively. In WGE, large mammographic lesions carry a significant risk for
      radiologically incomplete excision, while pathologically large and multifocal
      tumors may be histologically incompletely excised, especially if the excision
      does not extend down to the pectoral fascia. The excision sites of multifocal
      tumors should be re-excised because of the considerable risk of residual disease.
      The radiologic and histologic margins of the specimen may be misleading.

PMID- 14965556
TI  - Adjuvant chemo-hormonal therapy with cyclophosphamide, doxorubicin and 5
      fluorouracil (CAF) with or without medroxyprogesterone acetate (MPA) for node
      positive cancer patients, update at 12 years follow up.
AB  - An update with 10 years of follow up of a study adding adjuvant MPA to CAF
      chemotherapy is presented. A total of 409 patients were entered, of which 200
      were randomized to receive 500 mg of MPA i.m. on days 1-28 and twice per week
      thereafter for 6 months. There was a significant improvement in metastases-free
      and overall survival in women >60 years of age receiving MPA (P=0.01 and P=0.02
      respectively). A detrimental effect of MPA was seen in women <40 years. Possible
      reasons for these results are discussed.

PMID- 14965557
TI  - The diagnosis of invasive lobular breast carcinoma. Does MRI have a role?
AB  - Invasive lobular breast carcinoma accounts for approximately 15% of all breast
      cancers and is difficult to detect using conventional breast imaging techniques.
      We report a comparison between clinical, ultrasound scan (USS), mammographic and
      magnetic resonance imaging (MRI) of 22 patients with invasive lobular breast
      carcinomas. Actual tumour size was ascertained by histopathology. MRI detected 21
      of the 22 invasive lobular cancers whilst mammography and USS detected 16 and 20
      respectively. 19 tumours were clinically palpable. MRI was more accurate at
      assessing tumour size than USS and clinical examination, both of which
      underestimated tumour size.

PMID- 14965558
TI  - Neuregulin 1-alpha expression in locally advanced breast cancer.
AB  - The human Neuregulin 1 (NRG1) gene encodes several alternatively spliced ligands
      that bind to both c-erbB-3 and c-erbB-4, members of the family of type 1 tyrosine
      kinase growth factor receptors. Antibodies raised to a synthetic peptide
      recognize selectively the alpha variant of NRG1. The NRG1-alpha isoforms'
      expression was studied in 115 locally advanced adenocarcinomas of the breast
      using immunohistochemistry. Absent or low levels of NRG1-alpha were found to be
      associated with poorer prognosis compared to tumours that had moderate to high
      levels of the protein.

PMID- 14965559
TI  - Clinical and pathological findings of BRCA1/2 associated breast cancer.
AB  - It is not known if the behaviour of hereditary breast cancer (HBC) differs from
      that of sporadic breast cancer (BC). The aim of the present study was to analyze
      clinical-pathological characteristics in patients with BRCA1/2-mutation
      associated to BC. These data could be useful in the management of HBC. This study
      includes 17 patients with BC in whom a germ-line BRCA1/2-mutation was diagnosed.
      The patients were from 10 different families, and four patients had no family
      history of BC or ovarian cancer (OC). The study of mutations was with the protein
      truncation test (exon 11 for BRCA1, exons 10 and 11 for BRCA2) and sequencing
      (the rest of exons). At diagnosis the mean age was 37 years (28-54). Only 3/17
      patients presented with involvement of axillary nodes; no patient was diagnosed
      with metastatic disease. All cases were infiltrating ductal carcinoma; two of
      them were medullary carcinoma. Histological grade was available in 13/17 cases,
      with grade III being the most frequent (12/13). Hormonal receptors were negative
      in 8/10 patients. The mean follow-up was 129 months (23-223). There were three
      local recurrences at 17, 108 and 151 months; and two distant relapses at 15
      months (complete remission) and 92 months. There were three diagnosed
      contralateral BC. Hereditary breast cancer has malignant pathological features,
      but the clinical behaviour may be less aggressive than sporadic breast cancer in
      the same age group.

PMID- 14965560
TI  - Myofibroblastoma and solitary fibrous tumour of the breast: histopathologic and
      immunohistochemical studies.
AB  - Thirteen mesenchymal tumours of the breast were reviewed histologically and
      immunohistochemically. Nine tumours (male:female ratio 5:4, average age 64 years)
      were classified as myofibroblastomas and presented as a single nodule (four) or a
      multilobular mass (five). They were composed of elongated cells with vesicular
      nuclei showing grooves, intranuclear inclusion, and small but conspicuous
      nucleoli resembling myofibroblasts seen in scar tissue. In six tumours,
      hypercellular zones alternated with paucicellular, hyalinized areas. The collagen
      pattern was dense, diffuse, and brightly eosinophilic in all neoplasms. The
      tumour cells were positive for desmin, actin, and vimentin in all nine lesions,
      and in six tumours a focal CD 34 positivity was also demonstrated. Four tumours
      (four female patients, average age 75 years) were classified as solitary fibrous
      tumours and consisted of well-circumscribed nodules. They were characterized by a
      monomorphic population of thin, spindled to ovoid cells with finely dispersed
      chromatin and inconspicuous nucleoli. The pattern of the collagen in these
      tumours was one of thick, brightly eosinophilic bands. These four tumours were
      negative for all markers tested except vimentin and CD 34. Although
      myofibroblastomas and solitary fibrous tumours of the breast share many
      morphologic features, there are enough differences in their cytologic composition
      and, most importantly, in their immunohistochemical profile to consider them as
      distinct entities.

PMID- 14965561
TI  - Has Calman-Hine succeeded? Analysis of breast cancer procedure loads per
      consultant firm before and after the Calman-Hine report.
AB  - The Calman-Hine report was published in the UK in April 1995. It recommended the
      reorganization of cancer services into high-volume specialist units. This study
      analyzes Health Episode Statistics from the West Midlands Region of the UK NHS in
      order to establish whether--for breast cancer--specialization is occurring. We
      believe it is. Each year since the start of our analysis (1992) the proportion of
      procedures performed by 'high-volume' firms increased. The number of firms
      undertaking breast cancer procedures fell.

PMID- 14965562
TI  - Symptomatic women with normal screening mammograms: is assessment by the breast
      screening programme justifiable?
AB  - Since the commencement of screening in 1988, the West of Scotland Breast
      Screening Programme has invited women with symptoms, but normal screening
      mammograms, for assessment. This paper reviews the results of 344 such
      assessments. Malignancy was detected in three patients; two had invasive
      carcinoma and one Paget's disease of the nipple. One woman underwent a benign
      excision biopsy. Three women returned to routine recall were subsequently
      diagnosed with breast cancer; one had Paget's disease, a second developed a true
      interval cancer, and a third a screen detected cancer six years later. Cancer
      detection rate in this group of women was approximately 1% in those assessed. The
      two women with invasive breast carcinomas had dense breasts and one view only was
      taken on screening. No cancers were detected in women complaining of lumps or
      dimpling who had normal fatty or mixed density mammograms.

PMID- 14965563
TI  - Axillary lymph node scarring and the association with tumour response following
      neoadjuvant chemoendocrine therapy for breast cancer.
AB  - We observed that the axillary lymph nodes of some of our breast cancer patients
      who received neoadjuvant chemoendocrine therapy (NCT) showed evidence of
      scarring. The purpose of this study is to determine whether such scarring exists
      and, if so, whether it is confined to neoadjuvant patients and may be related to
      response to therapy of the primary tumour. We examined the axillary lymph nodes
      of a consecutive series of 255 breast cancer patients, all of whom had undergone
      radical axillary dissection. Fifty-three had received NCT; the remainder formed
      the control group. A scar was defined as an area of cellular fibrous tissue >0.25
      mm in diameter and for each patient scar count, median size and score were
      recorded. Nodes with scars were stained immunohistochemically (IHC) with 2
      epithelial markers for the presence of occult micrometastases. The nodes of 20.7%
      of patients who had received NCT contained scars compared with 13.4% of controls.
      The median scar size was significantly greater in neoadjuvant patients (P<0.001)
      and within this group scar count and score were significantly higher (P=0.026 and
      0.020) in those with no or minimal evidence of residual primary tumour. Scars
      which were IHC-positive for micrometastases were almost exclusively confined to
      neoadjuvant patients. Our results suggest that axillary lymph node scarring does
      exist, but is not a common phenomenon. It is more significant in neoadjuvant
      patients and within this group is most marked in those with the greatest primary
      tumour response to therapy. We believe that scarring is likely to represent
      downstaging of axillary disease. A prospective study involving a larger group of
      patients receiving NCT is indicated, to confirm these preliminary findings and
      establish whether scarring has prognostic or predictive potential.

PMID- 14965564
TI  - Prognostic value of HER-2/neu and p53 expression in node-positive breast cancer.
      HER-2/neu effect on adjuvant tamoxifen treatment.
AB  - HER-2/neu and p53 expression, conventional clinical and pathologic prognostic
      factors, were evaluated in a retrospective series of 283 node-positive breast
      cancer patients. Overexpression was determined by immunohistochemistry in
      formalin-fixed paraffin-embedded tissue blocks. Twenty one percent were HER-2/neu
      positive and 40% p53 positive. HER-2/neu expression was related to axillary lymph
      node metastasis (P=0.014), inflammatory infiltrates (P=0.004), and the absence of
      oestrogen (ER) (P=0.0026) and progesterone (P=0.01) receptors (PR). p53
      expression was related to lymph node involvement (P=0.03), necrosis (P=0.036),
      absence of ER (P=0.028) and PR (P=0.065). p53 was not associated with outcome.
      HER-2/neu was an unfavourable prognostic factor for disease-free (DFS) (P=0.05)
      and overall survival (OS) (P=0.02) in univariate analysis. Multivariate analysis
      showed that the number of involved axillary nodes (P<0.00001), age (P=0.004),
      grade (P=0.04), and PR (P=0.04) were independent predictors for OS. ER-positive
      patients treated with adjuvant tamoxifen had shorter DFS and OS when they were
      HER-2/neu positive.

PMID- 14965565
TI  - Validity of radiological examinations of patients with breast cancer in different
      age groups in a population based study.
AB  - By studying which radiological examinations had been performed before breast
      cancer operations the aim was to assess, how much benefit ultrasonography (US)
      and fine or core needle biopsy (FNAB, CNB) gave in addition to mammography, and
      whether the sensitivity of these examinations varied with the age of the patient.
      There were 659 consecutive histologically and six cytologically verified breast
      cancer cases included in the study. Information on mammography, US and FNAB
      findings were retrieved from the original patient files and classified as
      malignant or benign. The sensitivity (Se) of these was compared in three age
      groups (26-49, 50-59 and 60-92). Seventeen (3%) tumours had operations without
      any radiological examination and 73 (11%) without cytological or histological
      verification. The sensitivity of mammography (Se=0.92) was statistically
      significantly higher than the sensitivity of FNAB (Se=0.85, P=0.002) or US
      (Se=0.86, P=0.003). The sensitivity of mammography increased with age; US
      sensitivity was slightly higher amongst younger than older patients; the
      sensitivity of FNAB did not depend on the age of the patient. The sensitivity
      using a cutoff level of class 5 for mammography was higher (50% typical malignant
      findings) than for US (45%) or FNAB (30%). Among cases with benign mammographic
      finding (classes 1-2), the US finding was malignant (classes 3-5) in 4% and FNAB
      was malignant in 7%. Mammography is a reliable method of breast examination
      especially for women over 50 years of age. Ultrasonography is beneficial,
      particularly in younger women, but it is mainly performed as a complementary
      examination to a mammography and therefore could not be evaluated as an
      independent examination. FNAB and CNB results were not related to the age of the
      patient.

PMID- 14965566
TI  - Sentinel lymph node biopsy in impalpable breast cancer.
AB  - Sentinel lymph node biopsy has been investigated using combined radioactive
      colloid and supra vital blue dye in 27 patients with impalpable breast cancers.
      Sentinel nodes were identified in 25 cases (93%). Seven patients had involved
      nodes of whom all had a positive sentinel node. Sentinel node biopsy is ideally
      suited for use in impalpable breast cancers.

PMID- 14965567
TI  - Importance of local aromatase activity in hormone-dependent breast cancer: a
      review.
AB  - The cytochrome P-450 enzyme complex aromatase is the rate-limiting step in the
      production of oestrogens. It catalyses the conversion of androgens to oestrogens.
      In the treatment of hormone-dependent breast cancer in postmenopausal women,
      aromatase is the target for treatment with aromatase inhibitors. Recently
      registered aromatase inhibitors like anastrozole, letrozole and exemestane have
      proven to be effective therapy for advanced breast cancer in postmenopausal
      patients failing to respond to treatment with tamoxifen. Intratumoural aromatase
      activity has predictive value for response to treatment with aromatase
      inhibitors. Attempts are being made to find an immunohistochemical technique to
      determine aromatase in tumour tissue, which may serve as a predictive factor. In
      situ oestrogen synthesis through local aromatase activity in the tumour and
      adjacent tissue is probably a very important growth-stimulating system in hormone
      dependent breast cancer. This synthesis can be blocked with aromatase inhibitors.
      The regulation of aromatase activity and the cell types that contribute to this
      process are the subject of extensive research. There seems to be a complex
      interaction between malignant cells and adjacent cells in which factors such as
      IL-6 and its soluble receptor, TNF-alpha and prostaglandin E2 play an important
      role in stimulating aromatase activity.

PMID- 14965568
TI  - Interval breast cancer: is it a different type of breast cancer?
AB  - We have compared tumour type, tumour size, tumour grade and axillary lymph node
      status in three groups of women, 230 interval breast cancers (IC) in the West
      Sussex Breast Screening programme and 625 screen detected (SD) cancers and 916
      symptomatic (S) cancers treated at Worthing Hospital between July 1989 to April
      1996. Our true interval cancer detection rates were 5.28, 11.28 and 15.3 per
      10,000 screened women for the 1st, 2nd and 3rd year after screening. The
      proportionate incidences of true interval cancer were 29%, 61% and 82% for the
      1st, 2nd and 3rd year, similar to others' programmes in UK. In our programme a
      large proportion (42%) of IC and more than half of the true IC presented in the
      3rd year after screening. Out of 230 interval cancers, 40% (90) were
      unclassifiable, the remaining 60% (140) were classified as: True interval cancers
      (T) 54% (76), False Negative Subtle (FNS) 12% (16), Occult (O) 12% (17), and 22%
      (31) as False Negative (FN). Analysis of interval cancers according to their
      classification did not demonstrate any significant difference with respect to
      tumour size (chi2 5.59, df 4, P=0.22), tumour grade (chi2 5.29, df 4, P=0.25) and
      axillary node status (chi2 3.16, df 4, P=0.53) thus establishing interval cancers
      as a single group. Invasive ductal carcinoma of no specific type was the main
      tumour type in all three groups. Analysis of variance (ANOVA) showed significant
      differences in size between the groups (df 2, F=71.36, p<0.0001). Symptomatic
      cancers were 1.19 times the size of IC while SD were 0.83 times the size of IC.
      The difference in groups in terms of tumour grade was significant (Kruskal-Wallis
      test chi2 33.31, df 2, P<0.0001). The incidence of grade 2 tumours was similar in
      the three groups while a third of the IC and S were grade 3 tumours. Comparison
      of axillary node status showed a significant difference between the three groups
      (chi2 26.59, df 2, P<0.0001). When means and 75th percentiles were compared IC
      had the greatest number of positive nodes while SD had the smallest number of
      positive nodes. Interval cancers are the middle spectrum between symptomatic and
      screen detected breast cancers and represent small cancers (<10 mm) not detected
      at the time of screening and de novo cancers developing in the screening
      interval. The need for improving the sensitivity of current screening methods and
      identifying newer methods of breast cancer detection is highlighted by our study.

PMID- 14965569
TI  - 99mTc-MIBI scintimammography as a complement of the mammography in patients with
      suspected breast cancer. A multicentre experience.
AB  - The aim of this work has been to evaluate the clinical usefulness of 99mTc-MIBI
      scintimammography, used as a complement to mammography, in the study of patients
      with suspected breast cancer. We performed prone breast scintigraphy in 253
      patients (268 lesions) with suspected breast cancer. The size and degree of the
      suspected breast cancer was evaluated by mammography. Diagnosis was established
      by biopsy. Malignancy was diagnosed in 155 lesions and benign diseases in 113.
      The results of the scintimammography were a sensitivity of 91%, a specificity of
      71%, PPV=81% and NPV=85%. In lesions smaller than 1 cm, sensitivity and
      specificity were 57% and 100%; in lesions with a diameter of between 1 and 2 cm,
      these figures were 90% and 72% respectively, and in lesions of more than 2 cm the
      sensitivity was 99% and the specificity 50%. On mammography, 155 lesions were
      considered as having a high suspicion of malignancy, whilst 72 were indeterminate
      and 41 had a low probability. In lesions with a low or indeterminate suspicion of
      malignancy on mammography, the sensitivity and NPV of the scintimammography were
      97% and 98%. Scintimammography is a useful technique in the study of lesions
      where breast cancer is suspected. Scintimammography results are closely related
      to tumour size and the degree of mammographic suspicion. Scintimammography can be
      useful where mammography identifies lesions with a low or indeterminate suspicion
      of malignancy.

PMID- 14965570
TI  - Breast volume assessment: comparing five different techniques.
AB  - Breast volume assessment is not routinely performed pre-operatively because as
      yet there is no accepted technique. There have been a variety of methods
      published, but this is the first study to compare these techniques. We compared
      volume measurements obtained from mammograms (previously compared to mastectomy
      specimens) with estimates of volume obtained from four other techniques:
      thermoplastic moulding, magnetic resonance imaging, Archimedes principle and
      anatomical measurements. We also assessed the acceptability of each method to the
      patient. Measurements were performed on 10 women, which produced results for 20
      breasts. We were able to calculate regression lines between volume measurements
      obtained from mammography to the other four methods: (1) magnetic resonance
      imaging (MRI), 379+(0.75 MRI) [r=0.48], (2) Thermoplastic moulding, 132+(1.46
      Thermoplastic moulding) [r=0.82], (3) Anatomical measurements, 168+(1.55
      Anatomical measurements) [r=0.83]. (4) Archimedes principle, 359+(0.6 Archimedes
      principle) [r=0.61] all units in cc. The regression curves for the different
      techniques are variable and it is difficult to reliably compare results. A
      standard method of volume measurement should be used when comparing volumes
      before and after intervention or between individual patients, and it is
      unreliable to compare volume measurements using different methods. Calculating
      the breast volume from mammography has previously been compared to mastectomy
      samples and shown to be reasonably accurate. However we feel thermoplastic
      moulding shows promise and should be further investigated as it gives not only a
      volume assessment but a three-dimensional impression of the breast shape, which
      may be valuable in assessing cosmesis following breast-conserving-surgery.

PMID- 14965571
TI  - Prediction of cosmetic outcome following conservative breast surgery using breast
      volume measurements.
AB  - This study was undertaken to examine the feasibility of breast volume estimation
      as a predictor of cosmetic outcome. We looked at the cosmetic result of
      conservative surgery related to the percentage of breast tissue removed. The
      breast tissue excised was calculated by comparing the breast volume, calculated
      from the mammogram, and the specimen volume. A total of 24 patients were recalled
      to a special clinic and were assessed for their cosmetic result by the clinician,
      independent observer and the patient. The assessment was based on a scale of 1 to
      4 (poor to excellent). Our results show that if less than 20% of the breast was
      removed, all assessors felt that the cosmetic result was at least fair. If more
      than 20% of the breast was removed, the cosmetic score was poor as assessed by
      the clinician and independent observer. When excision of greater than 20% of
      breast tissue is anticipated, then a breast reconstruction procedure should be
      considered, if cosmetic outcome is to be enhanced.

PMID- 14965572
TI  - Symptomatic benign breast disease and hormone replacement therapy.
AB  - The effect of hormone replacement therapy (HRT) on presentation and diagnoses of
      post-menopausal women has been examined by a retrospective review of patients
      presenting to a symptomatic Breast Clinic over a 5-year period. Sixty-seven post
      menopausal women aged less than 65 years taking hormone replacement therapy for
      more than 6 months were compared with 144 post-menopausal women aged less than 65
      years not taking hormone replacement therapy. There was no difference in the
      pattern of presentation, rate of intervention or final diagnoses between these
      two groups. HRT does not appear to effect the pattern of presentation of benign
      breast disease in post-menopausal women.

PMID- 14965573
TI  - False-negative findings of malignant breast lesions on preoperative magnetic
      resonance mammography.
AB  - The aim of this study was to evaluate causes and percentages of false negative
      diagnoses of malignant breast lesions on preoperative dynamic magnetic resonance
      mammography (MRM). MRM was performed in 223 patients with 234 histopathologically
      proven malignant breast lesions (193 invasive carcinoma, 41 CIS) which were
      analyzed prospectively by routine analysis prior to surgery and re-analyzed by
      specialists, retrospectively. False negative findings were re-evaluated with
      respect to contrast enhancement, size and shape of lesions, reading errors, and
      technical problems. Preoperative analysis missed 27 of 234 malignant breast
      lesions (sensitivity 88.5%) including 15 of 193 invasive cancers (sensitivity
      92%) and 12 of 41 CIS (sensitivity 71%). Five of 193 invasive cancers (four
      invasive lobular, one invasive tubular carcinoma) and five of 41 CIS lesions were
      missed due to delayed or no contrast enhancement. The remaining 17 false negative
      diagnoses were due to reading errors (n=8), previous core biopsies (n=3), metal
      induced artefacts (n=3), localization outside the field of view (n=1), incorrect
      injection (n=1) or movement artefacts (n=1). Using dynamic MR mammography, there
      were 4.3% slow contrast enhancing malignant breast lesions and a maximum
      sensitivity of 95.7% for detection of all malignant breast lesions (97.4% for
      invasive breast cancer, 87.8% for carcinoma in situ) can be achieved in a
      preselected preoperative population.

PMID- 14965574
TI  - Should surgeons as well as radiologists report mammograms in symptomatic
      patients?
AB  - This study compared the accuracy of interpretation by surgeons and radiologists
      of 1053 women who had two view mammography and a histological or cytological
      diagnosis of benign or malignant breast disease. Patients with large or locally
      advanced breast cancers who had definite clinical findings where radiology was
      not required to make a diagnosis were excluded. The sensitivity for radiologists
      was non-significantly greater (81%) than surgeons (78%), but specificity and
      positive predictive value was identical in the two groups of readers. Combining
      the reports of the radiologists and surgeons increased sensitivity to 85.4% which
      is a significant increase in the sensitivity of the radiologist alone, P =0.02.
      This study indicates that symptomatic mammograms should be read by surgeons as
      well as radiologists.

PMID- 14965575
TI  - What about the other breast? A review of a series of bilateral breast carcinomas.
AB  - The BreastScreen Queensland Brisbane Southside BreastScreen Service reports on a
      study of 10 cases of bilateral breast carcinomas from a total cancer population
      of 217 cases. All cases were patients of screening examinations that were
      recalled for a suspicious lesion in one breast. Two cases were mammographically
      suspicious of bilateral tumours. In eight cases, tumours were ultrasonically
      visible in both breasts and in two further cases, the suspicion of bilateral
      malignancy was raised by the presence of bilateral microcalcification. It is not
      the purpose of this paper to provide a statistical analysis of the occurrence of
      bilateral breast cancer. This is a radiological paper from a breast screening
      service reporting on findings that conventional wisdom may find unusual. The
      incidence of bilateral breast malignancy in the study was found to be somewhat
      higher than expected. These cases have been diagnosed by the utilization of a
      particularly high standard of ultrasound and mammography, performed and
      interpreted by diagnosticians possessing an elevated level of suspicion of the
      possible presence of a second primary lesion. It is therefore proposed that an
      increased rate of diagnosis of bilateral tumours is possible with an evolution of
      assessment protocols, combined with quality ultrasound and mammography.

PMID- 14965576
TI  - Morphologic changes in breast biopsies after duct endoscopy.
AB  - Duct endoscopy is a recent technique used for a direct view of the breast ductal
      system. The aim of this study is to determine any morphological changes in breast
      tissue attributable to low-pressure irrigation with saline solution that the
      technique requires. A total of 26 breast biopsies from patients who underwent
      ductal endoscopy before surgery were compared with 26 breast specimens from the
      retroareolar region. Breast specimens from duct endoscopy showed more frequent
      epithelial detachment (73%), epithelial loss (35%), periductal clefts (77%),
      stromal disaggregation (46%) and displacement of epithelial cells into the stroma
      (27%) than the control group in which epithelial detachment was seen in 4% of
      patients, periductal clefts in 15%, and stromal disaggregation in 15%. Epithelial
      loss and epithelial displacement where not seen in the control group. Although
      low-pressure fluid perfusion used for duct endoscopy induced morphological
      changes in breast tissue, these can easily be distinguished from malignancy, and
      are most likely to occur as the result of duct rupture.

PMID- 14965577
TI  - Predicting axillary lymph node metastases in patients with T1 infiltrating ductal
      carcinoma of the breast.
AB  - Factors which can predict an increased risk of axillary metastases in cases of T1
      breast cancer could help to identify those patients most likely to benefit from
      axillary surgery. This pragmatic study aimed to examine the ability of commonly
      reported tumour pathological features to predict axillary metastases. All cases
      of T1 infiltrating ductal carcinoma excised with ipsilateral axillary nodes over
      a 7 year period were reviewed retrospectively. Of the 639 cases, 197 (30.8%) had
      positive nodes. Axillary metastases were found with 66.3% of tumours showing
      vascular invasion but only 16.0% of those without vascular invasion. Following
      multivariate analysis, vascular invasion and tumour size were found to be
      independent predictors of positive nodes but tumour grade was not. The decision
      to perform axillary dissection in T1 breast cancer could be based on the presence
      of vascular invasion and the size of the primary tumour.

PMID- 14965578
TI  - Anatomical variants of the intercostobrachial nerve encountered during axillary
      dissection.
AB  - Recent reports have described attempts at preserving the intercostobrachial nerve
      in patients undergoing axillary clearance for breast cancer. However, the anatomy
      of the nerve encountered by the surgeon operating in the axilla has not been
      previously described in any detail. In this study, we were able to document the
      anatomy of this nerve in 45 out of 50 consecutive patients undergoing axillary
      clearance. We found the anatomy variable, but have illustrated six main variants.
      In addition, we were able to preserve the nerve in 40 out of 50 cases.

PMID- 14965579
TI  - Management of patients with intermediate (C3) cytology and a solitary breast
      lump.
AB  - The records of all patients who had a C3 result on fine needle aspiration
      cytology (FNAC) over a 3-year period were reviewed. Clinical and mammographic
      findings at presentation were correlated with histopathological diagnosis. Of 43
      patients, 32 patients underwent excision biopsy. Histology was benign in 25
      patients, eight patients had an invasive breast carcinoma, two a phyllodes tumour
      and one had widespread ductal carcinoma in situ (DCIS). All but two of the
      patients with invasive tumours had abnormalities on clinical examination or
      imaging. In two patients there was no clinical or mammographic suspicion of
      malignancy. A C3 breast cytology result must be taken seriously as it is
      frequently an indicator of underlying malignancy. These results suggest that
      definite histology should be obtained in all patients because of the unacceptably
      high false-negative rate of clinical and radiological assessment in this group.

PMID- 14965580
TI  - Evaluation of prognostic factors in male breast cancer.
AB  - We conducted an analysis on 41 cases of male breast cancer (median age 54 y;
      range 25-82 y) in Kuwait. Most (51%) were stage II cancers with 65% arising in
      the left breast. There were 5 (12%) T1 tumours, 23 (56%) T2 tumours and 13 (32%)
      T3/T4 tumours. They were mostly (95%) infiltrating ductal carcinomas; 97% were
      grade 2 or 3. Axillary lymph node involvement was found in 69%. Estimated 5-year
      survival rates were 67% and 58% for overall and relapse free survival
      respectively. Favourable prognosis was associated with age below 50y, clinical
      stage I and II, small tumour size (T1, T2), low tumour grade and absence of nodal
      involvement or distant metastases; nodal status and grade were independent
      factors for relapse free survival in multivariate analysis. In 18 cases, an
      immunohistochemical study showed some degree of tumour antigen reaction for ER in
      89% of cases, PR in 61%, pS2 in 44%, CathD in 72%, p53 in 56%, c-erbB-2 in 50%,
      Ki67 and PCNA in 100% and bcl-2 in 78%. There were significant associations
      between several of these factors but none influenced survival. Despite the high
      incidence of staining of ER, our data do not support the concept of an endocrine
      pathway that could be usefully antagonized with antioestrogens for therapeutic
      benefit, as in women.

PMID- 14965581
TI  - Invasive lobular carcinoma of the male breast: do we need to think of
      Klinefelter's syndrome?
AB  - Cancer of the male breast is generally seen in men over 60 years of age and, as
      in women, the commonest histological type is invasive ductal carcinoma. Invasive
      lobular cancers are seen very rarely because of the absence of lobules in the
      male breast. Genetic abnormalities such as Klinefelter's syndrome can increase
      the risk of breast cancer, and it is thought that there has to be some
      cytoarchitectural abnormality for development of lobular cancers in men.

PMID- 14965582
TI  - Can breast cancer Hsp 27 (Heat Shock Protein 27000) expression influence axillary
      lymph node status?
AB  - The expression of heat shock protein 27 (Hsp 27) in breast cancers correlates
      with stage of disease, the lower the stage the higher the expression, and with
      the presence or absence of lymph node metastases; lymph node negative patients
      being more likely to express Hsp 27 (P<0.04).

PMID- 14965584
TI  - Nuclear medicine and breast cancer: a review of current strategies and novel
      therapies.
AB  - While breast cancer is still increasing in frequency, new diagnostic procedures
      are now available to challenge existing procedures and to make diagnosis of
      breast cancer more accurate and reliable. Mammography remains the standard
      investigation to reveal disease in an asymptomatic population: it can also be
      used to diagnose breast cancer in symptomatic patients (e.g. those with palpable
      breast lumps) and for guiding fine needle aspiration (FNA). Because the majority
      of breast lumps are benign, the challenge is to distinguish benign from malignant
      lesions without the use of invasive methods and this has attracted nuclear
      medicine physicians and medical oncologists to investigate the role of
      scintigraphic procedures to identify which patients require FNA. This review
      attempts to shed light on the various scintigraphic methods available which are
      of potential practical use in the assessment of malignant breast disease as well
      as looking at the possible role of nuclear medicine in the treatment of advanced
      disease.

PMID- 14965585
TI  - Exemestane: a review of its clinical efficacy and safety.
AB  - Aromatase inhibitors and inactivators are playing an increasing greater role in
      breast cancer treatment. Exemestane, a highly specific, steroidal aromatase
      inactivator, is the newest agent in this class. The drug is highly specific, and
      inhibits the in vivo conversion of androstenedione to oestrone (aromatization) by
      a mean of 97.9%. Exemestane has shown good efficacy and tolerability in multiple
      clinical trials among patients with metastatic breast cancer who have failed one
      or more previous hormonal therapies. Exemestane 25 mg/day slows disease
      progression and reduces tumour-related signs and symptoms and the drug exhibits a
      partial lack of cross-resistance with the non-steroidal aromatase inhibitors.
      Response rates to exemestane of 14% to 29% were observed including patients with
      visceral metastases, who have historically proven difficult to treat. In a large
      phase III trial, exemestane was found to be superior to megestrol acetate with
      respect to time to progression and overall survival. In addition, exemestane is
      currently under investigation as first-line therapy in metastatic disease and in
      sequence with tamoxifen in the adjuvant setting. Adverse events include low-grade
      hot flashes, nausea, and fatigue--mostly of mild to moderate intensity--and
      treatment-related discontinuations are rare. In conclusion, exemestane represents
      a novel and interesting drug for the treatment of advanced breast cancer, with
      exciting prospects for use in adjuvant therapy and, potentially, breast cancer
      prevention.

PMID- 14965586
TI  - Interpretation of the breast screening trials: a commentary on the recent paper
      by Gotzsche and Olsen.
AB  - This paper reviews and rebutts the recent criticisms of breast screening trials
      published earlier this year in the Lancet.

PMID- 14965587
TI  - Implications of extranodal spread in node positive breast cancer: a review of
      survival and local recurrence.
AB  - An evaluation of extra nodal spread (ENS) in predicting overall survival and
      locoregional relapse rates in 311 node positive breast cancer patients was
      undertaken: the study group comprised 71 patients with ENS and the control group
      comprised 240 patients with no ENS. A review of pathology reports that described
      ENS was performed and a scoring system to categorize focal involvement, extensive
      axillary fat involvement, and positive axillary surgical margins was devised.
      Median follow up time was 3.1 years. Overall survival, disease specific survival
      and disease-free survival rates were significantly worse in the study group in
      comparison with the control group. Poorer survival with more extensive
      pathological invasion of ENS was demonstrated. Multivariate analysis of disease
      specific survival in those patient with 1-3 involved lymph nodes demonstrated
      that ENS positivity was prognostically significant (P=0.013). Although
      locoregional relapse was increased in the presence of ENS, axillary relapses were
      uncommon and do not warrant axillary radiation.

PMID- 14965588
TI  - A new surgical strategy for breast conservation in locally advanced breast cancer
      that achieves a good locoregional control rate: preliminary report.
AB  - The scope of breast conserving surgery has recently expanded to include locally
      advanced breast cancer (LABC) patients who are downstaged following neoadjuvant
      chemotherapy (NACT). However, the efficacy of this approach in achieving adequate
      locoregional control of disease is in doubt. Some reports have attributed the
      failure to the association of NACT-induced tumour downstaging which can leave
      multifocal in situ and invasive lesions around the main tumour mass. In the
      present study, in order to eradicate all possible tumour satellites, a very wide
      local excision that included the whole original tumour-bearing area was performed
      regardless of the expected wide defect. This defect was then immediately
      reconstructed by an ipsilateral pedicled latissimus dorsi myocutaneous (LDM)
      flap. The study included 26 patients with LABC without evidence of primary tumour
      multicentricity. Tumours were downstaged following NACT. The early cosmetic
      outcome was good in the majority of cases. Early complications were minimal.
      Twenty-two patients had a mean follow up period of 30.2 (range 7-50) months. In
      those evaluable cases, locoregional control of the disease was excellent (100%)
      but distant metastases occurred in seven cases (31.8%).

PMID- 14965589
TI  - A key to understanding postoperative lymphoedema: a study on the evolution and
      consistency of oedema of the arm using ultrasound imaging.
AB  - Post-mastectomy oedema is a very serious complication that, in the course of
      time, will transform into fibrotic tissue. The aim of our study is to evaluate
      when and in which layer liquid oedema transforms into fibrotic tissue. To do so,
      ultrasonographic images were taken of 22 patients and 9 control women at the
      shoulder and 10 cm proximal and distal from the olecranon, with the images then
      being scanned and imported into a computer program to determine echogenicity of
      the dermis, subcutis, subcutis on dermal side and subcutis on fascial side.
      Statistical analyses were performed by means of the Wilcoxon test and a Student's
      t-test. No significant differences (P< or =0.05) were found for the different
      parameters in the control group. In the experimental group: significant
      differences in perimeter, skinfold, thickness of dermis and subcutis were found.
      Although not significant, subcutaneous tissue was more echogenic on the
      oedematous side, with significant hyperechogenicity at the fascial subcutaneous
      layer. This indicates that fibrotic tissue develops distally in the forearm.

PMID- 14965590
TI  - Breast carcinoma with osteoclast-like giant cells: morphological and
      ultrastructural studies of a case with review of the literature.
AB  - Primary carcinoma with osteoclast-like giant cells is a very rare tumour of the
      female breast. The clinical course, histological, immunohistochemical and
      ultrastructural features of 61 cases of invasive duct carcinoma with osteoclast
      like multinucleated giant cells (OMGCs) are reviewed and a new case is presented.
      The median patient age of all patients included in the review was 42 years, the
      tumour was located in the upper outer quadrant and the mammographic and gross
      findings were of a well-defined tumour of dark-brown colour, resembling a
      metastatic melanoma. Follow-up data in the literature have shown that 86% of
      patients with these tumours are still alive after 5 years. Histologically, these
      tumours are invasive ductal carcinomas with OMGCs next to the neoplastic glands
      and within their lumen. Signs of recent and past haemorrhage are ubiquitously
      present in the highly vascularized stroma. Immunohistochemical and
      ultrastructural studies have claimed a benign histiocytic nature of the OMGCs;
      they may represent a special type of polykaryon, distinct from both osteoclasts
      and inflammatory giant cells.

PMID- 14965591
TI  - Micrometastasis to axillary lymph nodes and bone marrow in breast cancer
      patients.
AB  - The axillary lymph nodes of 100 lymph node-negative breast cancer patients with
      known bone marrow status have been re-examined to explore the presence of
      micrometastasis in lymph nodes and the covariance of micrometastasis to bone
      marrow and lymph nodes. Nodes were serially sectioned at three intervals of 100
      microm, followed by immunohistological (two sections) and haematoxylin-eosin
      staining (one section). Tumours were mainly T1 and T2, and the patients had on
      average 13 (4-22) lymph nodes removed. In two patients, micrometastasis was
      detected in one node. Another 25 patients possessed single positive immunostained
      cells mimicking tumour cells. These cells have been shown to be false positive
      cells by Perl and melanin staining. One patient had metastasis to several nodes
      missed by the original examination. Immunocytochemical detection of
      micrometastasis in bone marrow revealed 11 marrow-positive patients. This study
      has identified a low frequency of micrometastasis to lymph nodes, and no
      covariance with micrometastasis in the bone marrow was seen. Bone marrow
      micrometastasis may be an independent prognostic variable, separate from axillary
      node status.

PMID- 14965593
TI  - Sentinel node biopsy in breast cancer--a need for randomized trials.

PMID- 14965592
TI  - Ovarian steroids and control of proliferation in the normal human breast.
AB  - Until recently, there has been considerable uncertainty as to how, or even which
      of the ovarian steroids influence human breast luminal epithelial cell
      proliferation. It is important that this is known because increased proliferative
      activity of this particular cell population is associated with increased risk of
      breast cancer. Review of the available literature suggests that while oestradiol
      is the major steroid mitogen in pre-menopausal women, the role of progesterone
      becomes more significant after the menopause when oestradiol levels are reduced.
      Moreover, recent studies have given new insights into the mechanisms by which
      oestradiol and progesterone exert their effects. This knowledge may allow
      development of new strategies for predicting breast cancer risk or preventing the
      disease.

PMID- 14965594
TI  - Sentinel node biopsy should be introduced into routine practice before results of
      randomized trials are available.

PMID- 14965595
TI  - Sentinel node biopsy in breast cancer--the view from Australia and New Zealand.

PMID- 14965596
TI  - Sentinel lymph node biopsy: an American perspective.
AB  - The current protocol for use of sentinel lymph node biopsy at Memorial Sloan
      Kettering Cancer Center, NY, USA is described. The technique requires to be
      validated both by individual surgeons and institutions prior to use. Ongoing
      American multi-institutional trials to investigate the true role of sentinel
      lymph node biopsy are underway.

PMID- 14965597
TI  - The association between induced and spontaneous abortion and risk of breast
      cancer in Slovenian women aged 25-54.
AB  - The risk of breast cancer may be increased by induced or spontaneous abortion.
      The evidence for this association was evaluated in a population based case
      control study in Slovenia, where 624 women aged 25-54 years with breast cancer
      diagnosed during 1988-1990 were matched for age and site of residence with
      controls randomly selected from the Slovenian Population Registry. Odds ratios
      (OR) and 95% confidence intervals (CI) were obtained by conditional logistic
      regression analyses. Spontaneous abortion was not associated with a significantly
      increased risk of breast cancer (nulliparous women: OR=1.41, 95% CI 0.22-9.01;
      uniparous women: OR=0.98, 95% CI 0.50-1.91; women with parity 2 or more: OR=1.40,
      95% CI 0.91-2.15). Induced abortion was not associated with a statistically
      significant elevated risk. The risk of breast cancer was higher in nulliparous
      women (OR=2.49, 95% Cl 0.68-9.09), and was less among women who had more
      deliveries. In uniparous women, the risk of breast cancer appeared higher when
      the induced abortion took place before a first full-term pregnancy (OR=1.94, 95%
      CI 0.70-5.39) rather than after a first full-term pregnancy (OR=1.22, 95% CI 0.71
      2.10) but neither of these odds ratios reached significance. We found no
      significant association between spontaneous abortion or induced abortion and
      breast cancer risk. This study found an elevated, but not statistically
      significant, risk associated with induced abortion among nulliparous women and
      among parous women when the induced abortion was before the first full-term
      pregnancy.

PMID- 14965598
TI  - Pre-operative estimation of primary breast cancer size: a comparison of clinical
      assessment, mammography and ultrasound.
AB  - This prospective study aimed to determine which is the most precise modality for
      the pre-operative measurement of primary breast cancers: clinical palpation;
      mammography; or ultrasound. Analysis of the difference between the measurement of
      the maximum tumour diameter by these three modalities and by the histological
      measurement was performed in 210 cases. Clinical palpation tended to overestimate
      tumour size and gave the largest standard deviation of the difference. Ultrasound
      and mammography both gave a similar standard deviation of the difference, with
      ultrasound tending to underestimate tumour size. For all modalities, the standard
      deviation and the 95% confidence intervals of the difference increased with
      increasing tumour size. There is little difference between the precision of
      ultrasound and mammography in measuring tumour size. The wide 95% confidence
      intervals for any method of pre-operative tumour measurement should be considered
      when planning patient management.

PMID- 14965599
TI  - Tc 99m-Sestamibi scintimammography in the differentiation of benign and malignant
      breast microcalcifications.
AB  - The capability of the mammography-scintimammography combination to distinguish
      between benign and malignant isolated clusters of breast microcalcifications is
      discussed. Scintimammography using Tc 99m-Sestamibi was performed in 97 women
      with an isolated cluster of microcalcifications on mammograms. Seventy-two women
      had final histopathologic diagnoses (24 cancer and 48 benign pathology). The
      other 25 patients had follow-up to 3 years. The results of mammography,
      scintimammography and mammography-scintimammography combination were divided into
      five groups, based on the suspicion of malignancy. The sensitivity, specificity,
      false negative fraction, false positive fraction, predictive positive value,
      predictive negative value and diagnostic accuracy were calculated varying the
      diagnostic threshold. The Receiver Operating Characteristic (ROC) statistical
      technique was employed to compare the diagnostic value of mammography to
      mammography-scintimammography combination. The area under the ROC curves was
      calculated by the Wilcoxon statistic without any hypothesis on data distribution.
      The detected difference between areas under the mammography ROC curve
      (area=0.854, standard error=0.049) and mammography-scintimammography ROC curve
      (area=0.897, standard error 0.033) was statistically significant (P>0.05, one
      tail). The area under a ROC curve represents the probability that a randomly
      chosen diseased or non-diseased subject could be correctly classified. From this
      point of view this paper demonstrates that, if properly used, scintimammography
      can add to mammography in the characterization of an isolated cluster of
      microcalcifications, even if it is not able to replace FNAB and core biopsy.

PMID- 14965600
TI  - High bone-mass density as a marker for breast cancer in post-menopausal women.
AB  - Bone mass has been proposed as a marker of cumulative exposure to oestrogen in
      women. We have studied the association between bone mass and breast cancer in
      postmenopausal women. In 126 cases of breast cancers and 126 controls, the bone
      mineral density (BMD) of the lumbar spine (L2-L4), femoral neck, trochanter and
      Ward's triangle was measured by dual-energy X-ray absorptiometry. All cases of
      cancer were confirmed by pathological reports. A questionnaire including
      information on reproductive history and other variables was collected. BMD was
      significantly higher among breast cancer patients than controls at all sites,
      except at the femoral neck where BMD was increased in the cancer group, but not
      significantly. After adjustment for potential confounding factors, the estimated
      relative risk of breast cancer in the highest quartile of BMD compared to the
      lowest quartile ranged from 2.5 to 4.8 for various sites of measurement. These
      results confirm that bone-mass density is a strong predictor for breast cancer in
      postmenopausal women. Women in the lowest quartile of bone mass appear to be
      protected against breast cancer. The mechanisms underlying this relation may be
      explained by cumulative exposure to oestrogen.

PMID- 14965601
TI  - Altered expression of epidermal growth factor receptor in non-involved tissue of
      cancer-containing breasts.
AB  - Previous studies have identified functional differences in non-involved breast
      tissue from cancer-containing breasts. This study has examined the expression of
      epidermal growth factor (EGFR) protein and mRNA in the non-involved breast of
      over 100 cancer-containing breasts and compared these with the same number of
      normal breast tissues from age-matched women with no history of breast cancer.
      Immunohistochemistry with EGFR1 antibody applied to frozen sections was used for
      the detection of protein, and in-situ hybridization using a digoxigenin-labelled
      oligonucleotide probe was the method for detecting mRNA. EGFR protein was
      detected in myoepithelial cells and to a lesser extent in epithelial cells, where
      it was predominantly basal or baso-lateral. There was a significant difference in
      the extent of staining in ducts and lobules between non-involved tissue from
      cancer-containing breasts and age-matched normal breasts, it being significantly
      greater in the latter (P<0.001). Labelling for EGFR mRNA was greater and more
      consistent in myoepithelial cells than epithelial cells overall. Differences were
      found for intensity of labeling, with it being significantly greater for normal
      breast tissue (P<0.001) than non-involved tissue from cancer-containing breasts.
      There is reduced EGFR expression in normal breast tissue from cancer-containing
      breasts when compared to age-matched breast tissue from women with no history of
      breast cancer. The mechanisms underlying this are unclear but in previous studies
      we have identified alterations in myoepithelial cells in cancer-containing
      breasts and the present findings may represent altered myoepithelial cell
      function.

PMID- 14965602
TI  - Biopathological significance of single cell DNA aneuploidy measured by static
      cytometry in breast cancer.
AB  - DNA ploidy image analysis in breast carcinomas has occasionally revealed cases
      with a diploid DNA content but with a single hypertetraploid element, the so
      called single cell aneuploidy (SCA). To identify the biologic significance of
      this little known phenomenon, we selected 40 cases with SCA from a series of 599
      consecutive operable breast carcinomas. The clinical, pathological and biological
      characteristics of SCA cases were compared with those of a control group of 40
      pure diploid breast carcinomas. Hormonal receptor status, proliferative indexes
      (Ki-67) and p53 overexpression were determined immunohistochemically and
      quantitatively evaluated by image analysis. The overexpression of c-erbB-2 was
      determined semiquantitatively. SCA was observed in 6.6% of cases (40 of 599) and
      in 17% of otherwise diploid cases (40 of 236). Breast cancers with SCA occur in
      younger women (mean age 54.75 y vs 61.12 y, P<0.05), are smaller (mean diameter
      20.00 vs 21.62 mm), less differentiated (percentage of G3 cases 13.2 vs 2.9),
      more frequently hormone independent (ER positivity 70.0 vs 77.5%; PgR positivity
      57.5 vs 77.5%) and have a greater cell proliferative activity (mean S-phase: 4.6
      vs 2.8, P<0.05), (percentage of Ki-67 immunostaining: 24.1 vs 19.7%). There is
      also more overexpression of c-erbB-2 and P53, particularly in pT1 cases in which
      the percentage of c-erbB-2 positive cells is 54 vs 32 (P value is not
      significant) and the percentage of p53 is 29 vs 4 (P<0.05). According to these
      results SCA may be a reliable marker of genetic instability and of greater
      biologic aggressiveness. Image cytometry of DNA content may be a cost effective
      means of identifying breast cancer patients with an increased risk of tumour
      recurrences despite otherwise favourable prognostic parameters.

PMID- 14965603
TI  - Fibroadenoma with atypical giant cells occurring in Li Fraumeni Syndrome.
AB  - This report describes a patient with Li Fraumeni Syndrome who first presented
      with an unusual fibroadenoma containing atypical multinucleated giant cells.
      These cells are thought to be fibrohistiocytic in nature and are rarely seen in
      fibroepithelial lesions of the breast. Previously these cells were considered
      incidental in nature. The possibility of Li Fraumeni Syndrome needs to be
      considered when such features are encountered in future.

PMID- 14965604
TI  - New mammographic stromal deformity: what is the significance of this finding on
      screening mammograms?
AB  - Current practice within the NHS Breast Screening Programme recommends surgical
      excision of screen detected areas of stromal deformity as differentiating
      carcinomas from radial scars and excluding in situ malignancy in association with
      radial scars is unreliable. We retrospectively reviewed all cases recalled for
      assessment over a 4 year period, identified to have an area of persistent stromal
      deformity not associated with surgical scarring and without an associated
      mammographic mass. Thirty women were prevalent (first) round screens--17 cases
      proved to be malignant and 13 benign. The latter group included three cases of
      atypical ductal hyperplasia. Nineteen women were incident (subsequent) round
      screens--all 19 cases proved to be malignant. This study supports the practice of
      surgically removing all areas of stromal deformity, particularly new areas of
      stromal deformity detected in the incident round, as in this group the likelihood
      of malignancy is extremely high.

PMID- 14965605
TI  - Successful treatment of radiation induced breast ulcer with hyperbaric oxygen.
AB  - The purpose of this report was to investigate the efficacy of hyperbaric oxygen
      treatment in the management of a persisting radiation induced ulcer following
      standard breast irradiation. A 57-year-old Caucasian patient was referred
      following partial mastectomy and axillary node clearance for a T2N0 grade 3
      infiltrating ductal carcinoma of the left breast. She received 45 Gy in 25
      fractions at 1.8 Gy per fraction to the isocentre to the whole breast using
      tangential fields and 4 MV photons, in conjunction with intravenous chemotherapy
      (cyclophosphamide, methotrexate and 5 fluorouracil). Treatment was interrupted
      for 3.5 weeks because of a grade 4 skin and subcutaneous reaction. Treatment
      resumed to the tumour bed alone. Chemotherapy was abandoned. The tumour bed
      received 14 Gy in 7 fractions at 2 Gy per fraction prescribed to the 100% using
      10 MeV electrons and a direct field, completing treatment on 7 July 1998. The
      radiation induced a painful 8x4 cm ulcer which persisted in spite of rigorous
      treatment including Gentian Violet, Silvazine Cream, Duoderm and antibiotics. The
      patient received 30 hyperbaric treatments, six times a week, completing treatment
      on 15 December 1998. The patient required insertion of bilateral ear grommets
      under local anaesthetic. The breast ulcer showed a response to treatment with
      early healing after 7-8 days and clinical evidence of re-epithelization. At
      completion of 30 treatments the patient was left with a small shallow faintly
      discharging multilocular 3-4 cm ulcer. The ulcer had completely healed by 14
      January 1999. The patient has been symptom free since completion of treatment.
      This report highlights the efficacy of hyperbaric oxygen therapy in the
      management of persisting radiation-induced ulcers.

PMID- 14965606
TI  - Fat necrosis of the breast: a cytological and clinical study.
AB  - Fat necrosis of the breast is a sterile condition that usually results from
      trauma to the breast. It may present with a breast lump that, on clinical and
      mammographic examination, can mimic malignancy. The literature suggests that fat
      necrosis of the breast can only be diagnosed accurately by histological
      examinations of breast biopsies. In this paper, we review the findings of a
      series of 35 patients in whom fat necrosis was diagnosed on fine needle
      aspiration cytology. Repeated fine needle aspiration cytology with close follow
      up have proven to be a reliable method of establishing the diagnosis of fat
      necrosis of the breast, thereby reducing the necessity for open biopsy.

PMID- 14965607
TI  - Pancolitis associated with docetaxel: a rare cause of megacolon.
AB  - The toxic effects of chemotherapy have been noted to cause a range of acute
      necrotizing colonic inflammatory disorders but until recently these have not been
      associated with docetaxel chemotherapy. Here we report a case of pancolitis
      presenting as megacolon following the administration of docetaxel for recurrent
      breast cancer.

PMID- 14965609
TI  - Matrix metalloproteinase inhibitors: past lessons and future prospects in breast
      cancer.
AB  - The matrix metalloproteinases (MMPs) play a central role in invasion and
      metastasis. However, despite striking activity in preclinical models, the
      clinical development of the matrix metalloproteinase inhibitors (MMPIs) has been
      difficult. The results of important phase III trials are now emerging and it is
      therefore opportune to review the current state of the MMPIs. In this article the
      evidence for the role of MMPs in the progression of breast cancer, the
      development of the MMPIs and the recent phase III results are discussed. Despite
      the problems encountered it is hoped that the MMPIs may yet provide another
      mechanism for the long-term control of micrometastatic disease. Furthermore,
      important lessons can be learnt from their development that are relevant to the
      development of other biological agents.

PMID- 14965610
TI  - Is there a role for iodine in breast diseases?
AB  - It is hypothesized that dietary iodine deficiency is associated with the
      development of mammary pathology and cancer. A review of the literature on this
      correlation and of the author's own work on the antioxidant function of iodide in
      iodide-concentrating extrathyroidal cells is reported. Mammary gland is
      embryogenetically derived from primitive iodide-concentrating ectoderm, and
      alveolar and ductular cells of the breast specialize in uptake and secretion of
      iodine in milk in order to supply offsprings with this important trace-element.
      Breast and thyroid share an important iodide-concentrating ability and an
      efficient peroxidase activity, which transfers electrons from iodide to the
      oxygen of hydrogen peroxide, forming iodoproteins and iodolipids, and so protects
      the cells from peroxidative damage. The mammary gland has only a temporary
      ability to concentrate iodides, almost exclusively during pregnancy and
      lactation, which are considered protective conditions against breast cancer.

PMID- 14965611
TI  - The role of needle biopsy in the diagnosis of breast lesions.
AB  - 14G core biopsy has contributed enormously to the pre-operative diagnosis of
      breast malignancy, although it is still subject to certain shortcomings. It is
      important to review core biopsy results in a multidisciplinary environment,
      especially when dealing with benign results, to minimize the potential for false
      negative cases. In certain circumstances, FNAC (fine needle aspiration cytology)
      still has an important part to play although this is very much dependent upon
      local circumstances. Decisions about the relative values of FNAC and core biopsy
      should be taken by the multi-disciplinary breast team within the context of its
      own results and practice, but should the use of FNAC be continued, the
      maintenance of the relevant expertise is of major importance. Vacuum assisted
      breast biopsy instruments should further increase the rate of preoperative
      diagnosis of impalpable lesions considered suspicious on mammography.

PMID- 14965612
TI  - Fat necrosis of the female breast--Hadfield re-visited.
AB  - Examination of pathology records from three hospitals over an 8-year period
      identified 42 cases of primary fat necrosis of the female breast. The mean age of
      the women was 56 (range 24-85) and the lump was most commonly in the upper, inner
      quadrant of the breast having been present for a mean of 11 weeks (range 1-56).
      Twenty-one percent of patients gave a history of trauma which had occurred a mean
      of 69 weeks (range 3-208) previously. The mammograms gave an appearance of
      malignancy in 12 of the 22 cases where they were performed. Cytology was
      suspicious in five cases. Thirty-seven patients subsequently underwent wide local
      excision to confirm the diagnosis. The histology was re-examined by a pathologist
      and a subgroup of patients were identified who had fat necrosis associated with
      periductal mastitis. Two patients who had a core biopsy diagnosis of fat necrosis
      were found to have malignancy on wide local excision. Here we review the changes
      in presentation since the original description of the condition, and highlight
      that although this series reflects difficult cases, fat necrosis remains a
      condition which can still be difficult to diagnose.

PMID- 14965613
TI  - A study of breast cancers detected in the incident round of the UK NHS Breast
      Screening Programme: the importance of early detection and treatment of ductal
      carcinoma in situ.
AB  - One hundred and seventy eight cancers detected on incident round screening in the
      UK National Health Service Breast Screening Programme were reviewed. Critical
      review of the immediately preceding screening films (from 3 years previously)
      found abnormalities at the site of the subsequently detected cancer in 93 cases
      (52%). Forty-eight of these (27% of the total) had microcalcification as the sole
      abnormality. All of these 48 women had invasive ductal carcinoma and/or ductal
      carcinoma in situ (DCIS) (including four cases in which DCIS was associated with
      another type of primary invasive breast cancer). The finding of
      microcalcification on the previous mammograms at the site of a subsequently
      detected cancer was a strong predictor for the presence of DCIS (with or without
      associated invasive disease) (P<0.0001). Of the women with invasive ductal
      carcinoma, those with microcalcification on previous films were significantly
      more likely to have intermediate or high grade (grade 2 or 3) tumours than those
      women without microcalcification on previous films (P=0.0015). Previous films
      were also read blind by two independent experienced breast radiologists. Cancers
      were correctly identified by one or both readers in 39 cases. However, 35 of the
      remaining 139 cases showed microcalcification which was not detected or
      considered significant by the readers. If only these 139 'true negative' screens
      are analysed, similar associations are seen between microcalcification on
      previous films and subsequent finding of DCIS (P=0.03) and between
      microcalcification on previous films and high grade invasive ductal carcinomas
      (P=0.015). These findings provide support for the hypothesis that
      microcalcification seen on previous screening films at the site of a subsequently
      detected invasive ductal carcinoma represents ductal carcinoma in situ. In this
      series, 19 of 82 women (23%) with invasive ductal carcinoma in the 'true
      negative' screen group had microcalcification suggestive of DCIS on mammograms
      taken, on average, 3 years previously. Significant microcalcification is often
      overlooked using current detection criteria. Early detection and treatment of
      DCIS is essential in order to prevent the development of aggressive invasive
      disease. Revision of the NHSBSP targets for DCIS detection is recommended.

PMID- 14965614
TI  - Presentation and diagnosis of adolescent breast disease.
AB  - Breast disease in the adolescent female is fortunately uncommon, with most
      presenting lesions being benign. The type and frequency of breast problems in
      young women less than 20 years of age are discussed in this paper. There were 634
      adolescent females (9-19 years) referred to the Wesley Breast Clinic between
      January 1990 and December 1999. Of these, 62.6% were aged 18-19 years. The
      commonest reason for referral was a lump or thickening in the breast (n=554,
      87.4%). Six hundred and nineteen females had ultrasound performed, with 59%
      showing no abnormality. The commonest abnormality in the remainder was probable
      fibroadenoma (n=162). Twenty-two percent of the females in the study had fine
      needle aspiration performed; none showed suspicious cytology. Twenty-three
      females had an excision biopsy following their initial visit. Three of these were
      found to have benign phyllodes tumour. There were no malignancies detected,
      although one female had previous DCIS diagnosed elsewhere.

PMID- 14965615
TI  - Intraductal component in invasive breast cancer: analysis of 250 resected
      surgical specimens.
AB  - The presence of an intraductal component together with an invasive carcinoma is
      known to be associated with a higher rate of local recurrence. The results of
      reviewing 250 resected surgical specimens from patients with breast cancer are
      reported. Two-hundred and fifty mastectomy specimens of invasive breast cancer
      were retrospectively analysed in order to determine intraductal components within
      the primary tumour as well as additional foci. In addition to the invasive
      carcinoma, a ductal carcinoma in situ (DCIS) of varying extent was identified in
      127 instances. The intraductal components were marginal in 27.6% of the cases,
      extensive in 61.4%, and predominant in 11.0%. In addition, 21 patients had
      isolated DCIS only. Such in situ components were more frequently found in the age
      group younger than 41 years and in premenopausal patients. Seventeen percent of
      carcinomas associated with an intraductal component were multicentric in location
      as opposed to only 5% of the breast lesions without an intraductal component. The
      highest proportion of residual tumour was seen in poorly differentiated invasive
      carcinomas with DCIS. Intraductal carcinomas with intraductal component tended to
      have a higher incidence of a positive surgical margin. Small carcinomas with an
      extensive in situ component require careful surgical management in order to
      achieve a tumour-free margin.

PMID- 14965616
TI  - IL-1 receptor type I expression in breast cancer.
AB  - The cytokine interleukin (IL)-1 is known to be involved in angiogenesis and
      metastasis. A prerequisite for IL-1 signalling is the presence of its receptor.
      Previously we have shown that glioblastoma cells express the IL-1 receptor type I
      (IL-1RI). In this study we analysed 11 breast tumour specimens for IL-1RI
      expression using the reverse transcriptase (RT) polymerase chain reaction (PCR).
      We found all the 11 breast tumours were positive for IL-1RI. This suggests that
      paracrine or autocrine produced IL-1 mediated signalling via IL-IRI might take
      place in breast tumours to control the production of pro-tumourigenic factors
      such as angiogenic factors and support further progression of tumour growth and
      metastasis.

PMID- 14965617
TI  - Palpable breast cancer which is mammographically invisible.
AB  - We have evaluated tumour characteristics, local recurrence rates and prognostic
      markers in 40 women with symptomatic palpable breast cancer proven by cytology,
      but in whom routine two-view mammography failed to detect a radiological
      abnormality. False negative mammograms were identified by cross-referencing all
      negative mammograms performed at the Royal Victoria Infirmary during the period
      1995-1999, with pathological records at the same institution. The average age was
      48 years. The majority of the tumours were invasive ductal carcinomas, 35 with an
      average size of 24 mm. There were 16 Grade II and 15 Grade III tumours.
      Lymphovascular invasion was seen in 18 on histology and six patients had distant
      metastases. Of those patients treated by conservation therapy there has been only
      one local recurrence, with a median follow-up of 18 months. We conclude that
      mammographically invisible tumours are of common histological type, are
      frequently high grade and node positive and occur mainly in the younger age
      group. However, BCT remains a viable option in the treatment of these tumours.

PMID- 14965618
TI  - Advanced breast biopsy instrumentation (ABBI) and management of nonpalpable
      breast abnormalities: a community hospital experience.
AB  - A range of diagnostic techniques have been in use for determining the nature of
      non-palpable mammographic abnormalities over the last decade, these include
      stereotactic and ultrasound guided cytology, core biopsy and vacuum assisted core
      biopsy techniques as well as open surgical breast biopsy. Recently, a less
      invasive alternative has been investigated; the Advanced Breast Biopsy
      Instrumentation (ABBI) technique (U.S. Surgical Corporation, Norwalk, CT). ABBI
      employs computer-guided stereotactic localization to target and excise
      mammographic lesions under local anesthesia, without the need for an operating
      theatre. We conducted a prospective review of all cases involving the use of the
      ABBI system during the first 17 months' of its use in a community hospital. One
      hundred and twenty six patients were referred for an ABBI procedure. One hundred
      fourteen ABBI procedures were performed on 113 patients (average age, 53 years;
      range, 33-82). The lesion was removed successfully in 113 of the 114 cases. Of
      the 114 lesions removed with the ABBI system, 88 were microcalcifications and 26
      were masses. Cancer was diagnosed in 21 patients (18%). Of the patients who had
      carcinoma, 11 (52%) had ductal carcinoma in situ, 9 (43%) had infiltrating ductal
      carcinoma, and 1 (5%) had infiltrating lobular carcinoma. Postprocedural
      complications occurred in 7 patients (6%); 4 had small haematomas, 2 had
      superficial wound infections, and 1 had an abscess. We conclude that the ABBI
      system, is an excellent alternative (to open biopsy after needle localization or
      large-core biopsy) for nonpalpable breast abnormalities. It has a relatively low
      complication rate and should be considered as part of the surgical armamentarium
      for the diagnosis of indeterminate nonpalpable mammographic lesions.

PMID- 14965619
TI  - Combined wide excision and mastopexy/reduction mammoplasty for inframammary
      hidradenitis: a novel and effective approach.
AB  - Hidradenitis suppurativa is a rare chronic skin condition involving the apocrine
      glandular zones, which are found predominantly in the axilla and inguinoperineal
      regions, but have been described at other sites, including the inframammary fold.
      Treatment requires complex surgical intervention with wide excision of involved
      tissue. Inframammary hidradenitis tends to affect young women and can prove
      resistant even to this radical form of surgery, which often results in marked
      scarring and breast deformity. We therefore decided to adopt a novel approach by
      incorporating the wide excision of inframammary skin currently necessary in a
      reduction mastopexy procedure. This enables primary closure with ptosis
      correction and should improve cosmesis. The reduction in the depth of the
      inframammary fold also makes hygiene easier in the long term. During a 6-year
      period, five patients (mean age 27 years) have been treated by this method. All
      patients had long-standing hidradenitis (mean 12 years), and had been treated
      with several courses of antibiotics. A modified Wise pattern reduction incision
      was used with a minimum amount of breast tissue being removed. In each case
      histology was consistent with hidradenitis. All wounds healed well and to date
      there have been no inframammary recurrences. The success of this operation in
      curing inframammary hidradenitis has had a dramatic affect on the lives of these
      young women and underlines the need for this rare condition to be treated in a
      specialist centre.

PMID- 14965620
TI  - Conservative surgery in breast cancer. Significance of resection margins.
AB  - We approached the issue of surgical margins in the conservative treatment of
      breast cancer by examining the literature germane to four precise questions: At
      what distance from the macroscopic margin of the tumour should the resection
      margin be? To what extent do histologically clear resection margins indicate
      complete local control of the disease? To what extent do histologically involved
      margins indicate persistence of disease? and Does the local recurrence rate
      correlate with the status of the resection margin? We propose categorizing margin
      involvement into five groups (absent, focal, minimal, moderate and extensive
      involvement) according to strict histological criteria, and assigning
      increasingly aggressive subsequent treatments according to the extent of any
      margin involvement.

PMID- 14965621
TI  - Incidence of second cancers among women with in situ carcinoma of the breast.
AB  - A population-based cohort of 371 women with carcinoma in situ (CIS) of the
      breast, collected by the Tuscany Cancer Registry, has been analysed for further
      invasive cancers. All cases, diagnosed between 1985 and 1997, have been followed
      up to the end of 1997. During 1707 person-years of follow-up, 27 further invasive
      cancers were diagnosed while 13.7 were expected (Observed/Expected=2.0, P<0.05).
      The relative risk for invasive breast cancers was 3.7 (P<0.05). According to the
      surgical treatment for CIS and the site of further invasive breast cancer, no
      side specific difference was evident. No significant increase was evident for
      other cancer sites; only non-melanomatous skin cancers occurred more frequently
      than expected (O/E=4.2). The cumulative risk of developing an invasive cancer
      after CIS was 13.2% at 10 years. There were also two deaths due to breast cancer
      (O/E=8.3; P<0.05) corresponding to a cumulative mortality risk of 2% at 10 years.
      We have quantified the risk of developing an invasive breast cancer among women
      with CIS of the breast as four times that of the general population.

PMID- 14965622
TI  - An unusually extensive case of Paget's disease of the nipple.
AB  - An unusually extensive case of Paget's disease of the nipple is presented. The
      patient had concealed the disease for over 10 years and was reluctant to accept
      treatment. A response was achieved with Tamoxifen. An initial complete response
      was obtained with radiation therapy, using an electron arc. Several plaques of
      recurrent disease developed in areas treated with less than 50 Gy, which have
      been controlled with the addition of superficial X-ray therapy. She remains well
      and disease-free 9 months following completion of treatment.

PMID- 14965623
TI  - Osteonecrosis of the femoral head following adjuvant chemotherapy for breast
      cancer.
AB  - We report a case of osteonecrosis in a patient treated with adjuvant chemotherapy
      for breast cancer. A 68-year-old woman presented with severe right hip pain.
      Seven months after completing a course of 6 cycles of adjuvant Cyclophosphamide,
      Methotrexate and 5-Fluorouracil with standard anti-emetic prophylaxis of
      Dexamethasone and Domperidone for a T2N0M0 breast cancer. Investigations revealed
      evidence of osteonecrosis of the right femoral head. Due to ongoing hip pain, she
      underwent an elective total hip replacement and her mobility has returned almost
      to normal. Osteonecrosis has been associated with corticosteroids and cytotoxic
      regimens which omit these agents. Osteonecrosis is a rare complication of
      cytotoxic therapy but with the increasing use of chemotherapy it should be
      considered in the differential diagnosis of joint pain in patients who have
      received anti-tumour therapies.

PMID- 14965624
TI  - Effectiveness and cost-effectiveness of double reading of mammograms in breast
      cancer screening: findings of a systematic review.
AB  - There is a lack of direct evidence on the effectiveness of double reading of
      breast screening mammograms within the context of national screening programmes
      even though about half of the countries that use mammography screening have
      implemented double reading. A systematic review was conducted to compare double
      reading with single reading of mammograms for screening accuracy, patient
      outcomes and costs. We searched an extensive range of electronic databases,
      bibliographies of studies were scanned and experts were contacted. Data
      extraction and quality assessment was undertaken independently by two reviewers.
      Estimates of the diagnostic accuracy were calculated for those studies with
      follow-up to identify interval cancers. Only 10 cohort studies met the inclusion
      criteria with reported extractable data on the effectiveness of double compared
      to single reading. The mix of methodologies meant that few conclusions could be
      drawn about the effect of double reading independent of number of views, or
      effects on size and type of tumours detected. Overall, double reading increases
      the cancer detection rate by 3-11 per 10,000 women screened and has a double
      impact on recall rates depending on the recall policy used. The benefit could be
      mainly in the detection of small cancers, and could be greatest where two readers
      have different strengths and weaknesses, or where readers are less experienced.
      Double reading can improve accuracy as compared with single reading. In
      particular, double reading by consensus or arbitration achieves an increase in
      cancer detection rate together with a reduction in the rate of women recalled for
      assessment. Further research should quantify the relative benefit from double
      reading according to recall policy and number of mammographic views, and estimate
      the impact on patient outcome.

PMID- 14965625
TI  - What is the evidence for a reduced risk of local recurrence with age among older
      patients treated by breast conserving therapy?
AB  - With the rising age of the population and the proposed extension of the breast
      screening programme to older women, increasing numbers of older patients are
      becoming eligible for breast conserving surgery and post-operative breast
      irradiation. Women over the age of 70 have traditionally been omitted from
      randomized controlled trials for assessing the role of breast radiotherapy after
      local surgery. The majority of trials suggest that local recurrence rates do
      decline with age. Similar conclusions are suggested by many non-randomized
      studies. Comparison of randomized and non-randomized studies is limited by
      differing extent of classifying tumour margins, nodal status, use of adjuvant
      systemic therapy, sample size, analytical approaches and duration of follow-up.
      Large randomized trials in older women are needed to assess whether, with careful
      attention to obtaining clear tumour margins, radiotherapy is required in low
      risk, ER positive, node negative breast cancer patients following wide excision
      and adjuvant tamoxifen. Within both randomized and non-randomized studies, only a
      few studies have failed to demonstrate an impact of age on recurrence rates
      following breast conserving treatment, with the majority finding a reduction in
      local recurrence rates with increasing age. Importantly for interpretation, no
      studies suggest that recurrence rates increase with age. The variation in
      analytical approaches and sample sizes are such that the variety of conclusions
      is not surprising. The results are compatible with a tendency for local
      recurrence rates to fall with age, but the variability is such that one cannot
      quantify this change with any precision.

PMID- 14965626
TI  - Comparison of immunohistochemical and biochemical measurement of steroid
      receptors in breast cancer: are both still necessary?
AB  - In our institute, the oestrogen and progesterone receptors of breast cancer
      samples are analyzed by biochemistry and immunohistochemistry. The purpose of
      this study is to evaluate and compare both techniques and establish whether one
      of them should be used in preference to the other. The probability of getting a
      positive or negative result with each technique was the same regardless of the
      method used as reference. The biochemical method uses a larger volume of tissue
      to determine the receptor status than immunohistochemistry. In some cases, this
      means a loss of valuable information. If we only use one technique, there is the
      potential to misclassify +/- 11% of patients. According to these results and in
      the knowledge that the major interest of steroid receptors' status remains in the
      domain of therapeutic decisions, we advise using immunohistochemistry first and
      biochemistry if there is a negative result. This would spare tumour tissue for
      new research studies.

PMID- 14965627
TI  - Computer-assisted immunocytochemical determination of breast cancer steroid
      receptors. Frozen sections vs paraffin sections.
AB  - Previously we have demonstrated that determination of oestrogen (ER) and
      progesterone (PR) receptors by immunocytochemical assay (ICA) on frozen sections
      (FS) and cytological smears with image analysis is effective for evaluating
      steroid receptors. The aim of this study was to determine concordance between ER
      and PR assessed by ICA on FS and paraffin sections (PS) both evaluated by image
      analysis. There were 115 breast carcinomas selected. For all cases, ER and PR
      determination was performed on FS and PS. Computer-assisted image analysis was
      performed using CAS 200. Results were expressed as percent positive area of
      neoplastic nuclei compared with total nuclear area of the examined neoplastic
      cells. Good correlation was demonstrated for both ER (r=0.759; concordance=83.4%)
      and PR (r=0.800; concordance=87.8%). The unexpected relatively low concordance
      for ER led to further investigations. We divided the 115 cases in two groups. The
      first group included specimens from our hospital; the second group specimens from
      suburban hospitals. In the first group there was better correlation for both ER
      (r=0.897) and PR (r=0.915) with a concordance of 91.5% and 93.6%, respectively.
      In the second group, correlation was worse for both ER (r=0.724) and PR
      (r=0.708), with a concordance of 77.9% and 83.9% respectively. From analysis of
      discordant cases we conclude that reduction in correlation and concordance with
      increased false negative cases in group 2 are probably due to delayed fixation.
      Our data suggest that ICA with automated image analysis is efficient in
      evaluating ER and PR on paraffin section only when the tumour samples are
      correctly fixed.

PMID- 14965628
TI  - The effects of oestrogens and anti-oestrogens on cognition.
AB  - Recent research suggests that oestrogen may play an important role in cognition.
      Epidemiological and experimental studies of hormone replacement therapy in post
      menopausal women suggest that oestrogen may be important to verbal memory in
      particular, as well as other cognitive functions such as attention and processing
      speed. Some studies have also suggested that HRT may have a beneficial effect for
      Alzheimer's disease, both in the prevention or delay of onset and that it is also
      of therapeutic benefit to patients in whom the disease is established. The use of
      selective oestrogen receptor modulators (SERMs) and other hormonal therapies for
      the treatment of breast cancer is common, yet few studies have examined the
      possible cognitive effects of this form of treatment. Several studies have shown
      cognitive decline in women receiving treatment for breast cancer, but the focus
      has been on the effects of chemotherapy. Further confusion has resulted from the
      diverse methodologies used in the existing literature. A pilot study to develop a
      suitable cognitive battery of tests for the evaluation of cognitive function in
      women receiving hormonal therapy for the treatment or prevention of breast cancer
      is introduced.

PMID- 14965629
TI  - Chemotherapy-induced histologic changes in mastectomy specimens and their
      potential significance.
AB  - The aim was to assess chemotherapy-induced histologic changes in breast cancer
      and to evaluate their relationship with tumour response, to treatment and patient
      survival. We examined paired pre- and post-chemotherapy tumour specimens from 57
      patients with stages II and III breast cancers. All patients received three to
      four courses of anthracycline-containing preoperative treatment and subsequently
      underwent modified radical mastectomy 3-5 months after diagnosis. Histologic
      parameters evaluated included extent of residual disease and cytologic changes in
      residual tumour and in non-neoplastic breast tissue and lymph nodes. Correlation
      of pathologic changes with disease-free and overall survival was evaluated.
      Clinical evaluation indicated that 24% (n=14) of patients had a complete
      response, 53% (n=30) had a partial response, and 22% (n=13) had stable disease.
      Pathologic assessment revealed a complete response in 14% (n=8) of patients.
      Clinical and histologic complete responses were discordant in 35% of patients.
      Sixty-eight percent of tumours demonstrated moderate to severe cytologic changes
      in the cytoplasm and nucleus of neoplastic cells. These were characterized by
      increased overall cell size, cytoplasmic vacuolization, nuclear enlargement,
      multinucleation, and vesiculation of chromatin. Chemotherapy-induced histologic
      changes varied within a tumour and between patients. Tumour cytologic changes
      were significantly associated with histologic (p=0.03) as well as clinical
      (p=0.02) tumour response. Pathologic tumour response, but not histologic changes,
      was also a powerful predictor of overall survival and relapse-free survival. In
      the non-neoplastic glandular tissue, periductal and perilobular fibrosis and
      atrophy of lobular acini similar to those seen in postmenopausal breast tissue
      were noted. Changes in lymph nodes were characterized by lymphoid depletion and
      fibrosis with and without tumour metastasis. Chemotherapy-induced cytologic
      changes are frequently seen in neoplastic breast epithelium and correlate with
      response to treatment. Histologic confirmation of clinical tumour response to
      preoperative chemotherapy is necessary for accurate characterization of
      patients', response to treatment.

PMID- 14965630
TI  - The technique of B-, S-, or W-reduction mammaplasty in the conservative therapy
      of breast carcinomas: experiences with a new surgical technique.
AB  - In 62 women with carcinomas of the breast and large and/or ptotic breasts,
      quadrantectomy as tumour resection with a wide tumour-free margin was combined
      with individually adapted reduction mammaplasty with B-, S-, or W-shaped
      incisions based on the B-plasty according to Regnauld. Though 25 carcinomas (40%)
      were larger than 2 cm and were situated mainly in the upper quadrants, in more
      than 75% of the cases the cosmetic results were good or very good. In eight cases
      a subsequent operation (secondary mastectomy, correction of nipple positions or a
      contralateral reduction) was necessary. Recurrence has not been observed so far.
      The techniques described allow symmetric breast reduction with removal of large
      amount of tissue regardless of tumour localization.

PMID- 14965631
TI  - Choices and information offered to patients undergoing immediate post-mastectomy
      breast reconstruction: a survey of patient opinion and self-assessed outcome.
AB  - For those patients who request breast reconstruction after mastectomy, the
      immediate procedure is becoming increasingly common. Whilst this option results
      in resource cost savings, and may have benefits for patients, little is known
      about the information offered to patients who are faced with a
      mastectomy/reconstruction decision. To investigate these concerns, and also to
      determine patients' own assessment of their outcome after immediate
      reconstruction, we carried out a retrospective survey of all patients who
      underwent an immediate breast reconstruction at this Centre over a 3-year period,
      utilizing a detailed study-specific questionnaire, together with two widely used
      health status instruments. The response rate was 92% (57 patients). Nearly all
      patients were found to have been offered the choice of a delayed procedure,
      should they wish it, but information about type and choice of prosthesis was
      considered by patients to be inadequate. Steps to address this have been
      implemented. Scores from the SF-36 Health Survey Questionnaire showed that this
      patient group was comparable with a normal female population for the dimensions
      of physical function, mental health, energy, and general health. However, social
      function was found to be significantly lower, and a substantial minority (46%)
      exhibited some anxiety as assessed by the Hospital Anxiety and Depression (HAD)
      Scale.

PMID- 14965632
TI  - Prevalence of self-reported arm morbidity following treatment for breast cancer
      in the Australian Breast Cancer Family Study.
AB  - Population-based women (n=1049) with breast cancer diagnosed mainly between 1996
      and 1998, when aged 20-59 years, were mailed a questionnaire seeking information
      about self-reported shoulder stiffness and swelling, numbness and pain/ache in
      the arm following treatment (excluding 6 months from diagnosis). Of the 809 who
      completed the survey, approximately seven in eight experienced at least one
      symptom, one in six reported all four symptoms, and one in three considered that
      their arm morbidity interfered substantially with activities of daily living. Arm
      swelling occurred at some time in 39% of women, was present in 20% 1 year, and in
      29% 4 years, after diagnosis. The prevalence of arm swelling was higher in women
      with axillary node dissection (OR=2.4; 95% Cl 1.0-5.6), and was increased in a
      women with a higher body mass index (P=0.02) and less education (P=0.01), but was
      not related to age, number of nodes excised or self-reports of radiation or type
      of surgery.

PMID- 14965633
TI  - Current treatment modalities of breast-cancer patients in Alexandria, Egypt.
AB  - Despite great advances in the treatment of breast cancer during recent years,
      many breast cancer patients still do not receive appropriate treatment. Data were
      collected during a 1-year period from nine general hospitals aiming at evaluating
      the quality of care delivered to breast cancer patients in Alexandria, Egypt. A
      total of 565 breast cancer patients were involved. The highest frequency of cases
      was diagnosed in stage II followed by stage III. Patey's modified radical
      mastectomy was the most commonly performed operation (82.65% of cases),
      regardless of the clinical stage or health facilities. Hormonal receptor status
      was rarely performed. There was no consensus regarding the type of systemic
      therapy (hormonal, chemotherapy or combined) to be administered for each clinical
      stage and menopausal status. Concerning postoperative radiotherapy, it was
      invariably the rule, regardless of the clinical stage. We conclude that, despite
      some improvement over the last few years (shorter diagnostic delay, larger use of
      standard classifications, and less radical surgery), the quality of management of
      breast cancer in Egyptian general hospitals is still not satisfactory.

PMID- 14965634
TI  - Primary leiomyosarcoma of the breast: diagnosis, management and outcome. A report
      of a new case and review of literature.
AB  - Primary leiomyosarcoma of the breast is very rare and represents a diagnostic
      challenge. Only 16 cases have been reported in the English language literature.
      We report another new case and have analysed reports of the previous cases aiming
      to present a simple evidence-based approach to the clinical, radiological and
      pathological diagnosis of this rare tumour. The average age of presentation is 56
      years. All neoplasms have been limited to the breast at the time of diagnosis.
      The usual presentation is a slowly growing mass, but in the current case report
      the patient present with mastalgia. There is always a possibility of local
      recurrence or distant spread, which can occur many years after primary surgery.
      Leiomyosarcoma must be histologically distinguished from leiomyoma and the
      presence of >3 mitoses per 10 high-power fields is usually indicative of
      malignancy. Immunohistochemistry is helpful to confirm diagnosis. As this is a
      slow-growing malignant tumour with a propensity for local recurrence, total
      mastectomy is the treatment of choice. The tumour is not hormone-dependent and
      hormone manipulation is not a treatment option.

PMID- 14965635
TI  - Thromboprophylaxis in patients undergoing surgery for breast cancer.
AB  - Patients undergoing surgery for carcinoma of the breast are thought to be at
      lower risk of developing thromboembolic complications than those with abdominal
      malignancies and the role of the thromboprophylaxis is unproven. To determine
      current thromboprophylaxis practice a questionnaire was sent to 184 consultant
      surgeons thought to be involved in breast cancer surgery, of whom 137 responded
      (74%). Eleven surgeons no longer dealt with breast cancer patients. Of the
      remaining 126, thromboprophylaxis was given routinely by 88 (69.8%), with the
      commonest regimens being subcutaneous heparin only (n=43) and heparin combined
      with compression stockings (n=20). Patients with breast cancer were regarded as
      being at high risk of thromboembolic complications by 65 clinicians in this group
      (73.7%). Thirty-eight consultants did not use thromboprophylaxis routinely, the
      most commonly stated reasons were low/no risk of DVT (n=24), because of early
      postoperative mobilization (n=20) and increased risk of bleeding complications
      (n=15). Twenty clinicians reported a total of 22 deep venous thromboses and two
      pulmonary emboli affecting patients under their care who had surgery for breast
      cancer during the preceding year. Almost 70% of surgeons routinely employ
      thromboprophylaxis in patients undergoing breast cancer surgery but practice
      varies widely.

PMID- 14965636
TI  - Factors that influence volume and duration of wound drainage after mastectomy and
      level III axillary node clearance.
AB  - Factors influencing drainage after operations for breast cancer remain
      controversial. The total volume and duration of drainage was prospectively
      measured in 252 women undergoing mastectomy and level III axillary clearance, and
      compared to patient, operative and tumour factors, using multivariate analysis.
      The total drainage and duration, respectively, correlated with the weight of the
      patient (r=0.39, P<0.01; r=0.29, P<0.01) and breast weight (r=0.37, P<0.01;
      r=0.29, P<0.01), and was predicted by the volume on the first postoperative day
      (r=0.58, P<0.01; r=0.50, P<0.01). There was no correlation with age, blood loss,
      length of operation, tumour size, number of axillary nodes retrieved, or whether
      nodes were involved by cancer. The volume and duration of drainage appear thus to
      be simply a function of the area of tissue planes opened.

PMID- 14965637
TI  - Calciphylaxis causing necrotizing mastitis: a case report.
AB  - Calciphylaxis is a rare condition most commonly related to ESRD and
      hyperparathyroidism. We report a case of necrotizing mastitis caused by
      calciphylaxis following routine breast biopsy for microcalcifications. Early
      recognition of the potential for this condition should help in clinical
      management of patients with calciphylaxis.

PMID- 14965638
TI  - Amlodipine gynaecomastia.
AB  - We report only the second published confirmed case of gynaecomastia caused by
      amlodipine (a dihydropyridine calcium channel blocker). Gynaecomastia developed
      in a 70-year-old male within 3 months of starting amlodipine, and symptoms
      resolved within 3 weeks of drug withdrawal suggesting a strong relationship
      between amlodipine and gynaecomastia in this patient. Recent research has
      suggested possible interesting novel mechanisms for amlodipine gynaecomastia,
      which are discussed.

PMID- 14965639
TI  - The impact of endocrine therapy on patients with breast cancer: a review of the
      literature.
AB  - This paper reviews studies which have examined the impact of endocrine therapy on
      the quality of life (QOL) of patients with breast cancer. In patients with
      primary disease, published studies suggest that endocrine therapies, such as
      tamoxifen, significantly increase both gynaecological and vasomotor symptoms.
      However, few studies have been able to demonstrate the impact which these
      symptoms have on patients' QOL. This failure can be partially attributed to a
      range of methodological problems. Psychosocial research in advanced disease has
      largely consisted of randomized controlled studies with QOL as one of several
      study endpoints. Second generation treatments, such as aromatase inhibitors, have
      frequently been compared with older treatments, such as progestin therapies.
      Unfortunately, QOL data reported in these studies have tended to be fairly
      limited. Problems with existing QOL research in endocrine treatment are discussed
      and recommendations are made for further work.

PMID- 14965640
TI  - Diagnosis of non-palpable breast cancer: a review.
AB  - The literature on several methods of diagnosing non-palpable breast carcinoma has
      been reviewed. Skin projection and dye are methods not frequently used. Several
      aspects of FNA biopsy/cytology, ultrasound-directed methods, frozen section and
      MRI localization procedures are highlighted and comparisons are made. Much
      attention is being payed to needle localization breast biopsy and stereotactic
      core needle breast biopsy. The management of patients with mammographic
      abnormalities is shifting from needle localization to breast biopsy stereotactic
      core needle biopsy. Items of comparison between the two mentioned methods are
      accuracy, indications, complications and costs. The role of the ABBI system in
      the management of breast cancer has not yet been defined. A cooperative effort
      between the mammographer, surgeon and pathologist is critical to a successful
      image-guided breast biopsy programme.

PMID- 14965641
TI  - Methods of ovarian suppression used in the UK.
AB  - Ovarian suppression in the management of breast cancer has had a resurgence in
      the 1990s. In view of the development of luteinizing hormone-releasing hormone
      (LHRH) analogues and advances in laparoscopic surgery, we wished to determine
      whether more consultants are considering these methods for achieving ovarian
      suppression than radiotherapy. A questionnaire was designed to determine the
      current practice of consultants in the UK and to discover who is involved in
      making this decision. It was distributed via the Adjuvant Breast Cancer (ABC)
      trials office to consultants who enter patients into the ABC premenopausal trial.
      Seventy-four (72%) questionnaires were analysed. The preferred method of
      treatment was radiotherapy in 60%, surgery in 30% and LHRH analogues in 9%.
      Seventy-three per cent of consultants were using more than one technique but did
      not always involve the patient in the decision-making process to determine which
      treatment modality to use. Radiotherapy techniques used included using bony
      landmarks for field borders (46%), using a standard field size (20%) or using
      ultrasound localization (15%).

PMID- 14965642
TI  - Incidence and prognosis in early onset breast cancer.
AB  - The aim of this study was to assess the incidence and prognosis in early onset
      breast cancer. Age-adjusted incidence and death rate for the 5394 Swedish women
      diagnosed with breast cancer under the age of 40 between 1960 and 1996 was
      studied using data from the Swedish Cancer Registry and Swedish Death Cause
      Registry. A total of 107 consecutive young patients with invasive breast cancer
      undergoing surgery during 1980-1993 in the Southeast Swedish health care region
      were retrospectively followed up and their cancers reviewed and graded blindly.
      The median follow-up time was 11.2 years. The applicability of the Nottingham
      Prognostic Index (NPI) as a prognostic tool was investigated. Grade, age, node
      status, tumour size, S-phase fraction and steroid receptor content were related
      to survival univariately and multivariately in a Cox proportional hazard
      analysis. The incidence of early onset breast cancer has increased moderately and
      the survival rate has not improved during the last 35 years. When young women are
      diagnosed with breast cancer their tumours are larger, their lymph nodes more
      often involved, and the median grade higher than in older with 64% having grade 3
      tumours. Lymph node status was the strongest sole prognostic indicator but the
      use of NPI gave more accurate prognostic information than node status alone.

PMID- 14965643
TI  - Accuracy of combined breast imaging in young women.
AB  - This is a study of the accuracy of combined breast imaging (mammography and
      ultrasound) in young women with breast symptoms. We performed an appraisal of the
      literature, and improved our study design by avoiding biases identified in
      published work. Our study presents the sensitivity and specificity of mammography
      and breast ultrasound, individually and in combination, using different
      thresholds for categorizing test results, in a population of consecutive women.
      We show that combining the two imaging tests does improve sensitivity without
      significantly reducing test specificity. However, the number of additional
      cancers correctly identified using combined imaging, relative to the number of
      false positives, is highly dependent on breast cancer prevalence.

PMID- 14965644
TI  - Scintimammography: a pictorial review of the variable normal, post surgical and
      pathological appearances.
AB  - Scintimammography has a high specificity and sensitivity for the detection of
      primary and metastatic breast carcinoma and in the evaluation of the
      postoperative breast. This review highlights the spectrum of pathological
      features as well as the normal postoperative and postreconstruction changes and
      the variable normal appearances that may be encountered with this technique.

PMID- 14965645
TI  - Preoperative axillary ultrasound scan: its accuracy in assessing the axillary
      nodal status in carcinoma breast.
AB  - The aim of this study is to report the accuracy of ultrasound scan in axillary
      node staging in breast carcinoma. Eighty-four patients with breast cancer
      attending a breast clinic were entered in this study and axillary ultrasound scan
      was performed using a 7.5 MHz probe. The sensitivity of ultrasound scan in
      detection of axillary nodal metastasis was 74% with a specificity of 89%,
      positive predictive value of 87%, negative predictive value of 84% and overall
      accuracy of 83%. The sensitivity was low (38%) when nodes were small or non
      palpable. The Likelihood Ratio (LR) for the test positive was 6.37 and the LR for
      the test negative was 0.29. The combined assessment (Clinical
      Examination+Ultrasound scan+FNA) of axillary node status was very sensitive--88%,
      with a specificity of 100%, positive predictive value of 100%, negative
      predictive value of 88% and overall accuracy of 92%. Ultrasound scan of axilla is
      a valuable method of preoperatively assessing axillary nodal status, and may
      prove useful in managing patients with breast cancer.

PMID- 14965646
TI  - The time-course of metastases from breast cancer after mastectomy and breast
      conserving surgery with and without isolated local-regional recurrence.
AB  - We have examined time intervals between events in 390 metastatic breast cancer
      (MBC) patients whose distant failure developed within 10 years from initial
      surgery of Stage I/II disease. All of the patients underwent axillary dissection
      and mastectomy (n=295) or breast-conserving surgery (BCS, n=95), between 1983 and
      1987. Distinctions have been made between distant failure with (n=79) and without
      (n=311) isolated local-regional recurrence (LRR). The median survival time after
      first relapse was significantly longer with intrabreast (30 months) and chest
      wall (24 months) than with distant relapse (15 months), but with axillary (17
      months) or with supraclavicular (17 months) relapse survival was similar. The
      delay between LRR and distant metastasis was shorter with axillary (7 months) and
      supraclavicular (9 months) than with breast (20 months) and chest wall (12
      months) recurrences. The median postmetastatic survival time by site of first
      relapse was significantly shorter with supraclavicular (6 months) and axillary (9
      months) than with distant site relapse (15 months) but with intrabreast (12
      months) or with chest wall (11 months) recurrence survival was similar. In MBC,
      regional recurrences are associated with a shorter interval between events than
      with local recurrences. The shortened intervals for patients with regional
      recurrence suggest that metastases existed at the time of initial surgery. The
      question of whether prevention of local or regional recurrence or both improves
      cause-specific survival after mastectomy or BCS needs to be answered in
      randomized studies.

PMID- 14965647
TI  - Latissimus dorsi mini-flap: a technique for extending breast conservation.
AB  - The latissimus dorsi (LD) flap was first used in patients for breast
      reconstruction in 1896. More recently it has been used to fill defects after
      quadrantectomy or very wide excision. We have developed a two stage procedure for
      excision of large breast cancers which would otherwise require mastectomy. The
      first stage is a wide excision of the cancer without removal of the overlying
      skin. Thirty patients with large localized operable breast cancer underwent wide
      local excision followed 5 to 10 days later in 25 patients who had clear
      histological margins by an axillary dissection with transfer of the LD muscle and
      overlying fat into the defect in the breast (mini-flap). The cosmetic outcome of
      these 25 patients who underwent mini-flap were compared with age matched patients
      having a standard wide local excision and axillary node clearance or mastectomy
      and immediate breast reconstruction. The volume of tissue excised in patients
      having their defects filled by LD mini-flap was significantly greater than those
      women undergoing standard wide excision, p<0.001. Compared with patients who had
      a mastectomy and immediate breast reconstruction, patients who had mini-flaps
      reported a better treated breast shape, p=0.04, a greater resemblance to the
      opposite breast, less self consciousness and less change in attitude of their
      spouse, p=0.03 and they were more likely to choose the same operation in future
      compared with patients having immediate whole breast reconstruction, p=0.02.
      Results as rated by patients in the mini-flap group were similar to those women
      treated by standard wide local excision. Only one patient in the mini-flap group
      felt sexually inhibited. When wide local excision and LD mini-flap is performed
      as a two stage procedure, it is an oncologically safe technique and extends
      breast conservation to women with larger tumours. The cosmetic outcomes appear
      better than those following the alternative of mastectomy and immediate breast
      reconstruction.

PMID- 14965648
TI  - Compression prophylaxis may increase the potential for flight-associated
      lymphoedema after breast cancer treatment.
AB  - This study aimed to assess exposure to flying in breast cancer survivors and
      assess the relationship of flying to lymphoedema. A total of 293 relapse-free
      breast cancer survivors with known pathology and treatment details and
      prospectively measured arm circumferences were surveyed for their flight exposure
      and precautions history. Of these, 287 responded, with a mean follow-up of 31.6
      (4-111) months. A total of 50.5% had flown, and of these, 27% had travelled
      overseas. The mean number of flights was 5.3 (1-100); 24% had taken lymphoedema
      precautions, 90% of which utilized compression techniques. There was no
      significant difference in lymphoedema rates for fliers (11.2%) and non-fliers
      (8.3%). No woman reported permanent (new or increased) swelling after flying. Of
      the nine reporting temporary swelling, six reported 1-3 concurrent potential risk
      factors. On regression modelling for both measured and self-reported swelling
      endpoints the use of precautions (OR 5.6 for lymphoedema and 3.7 for flight
      related temporary swelling) were statistically significant. For patient-reported
      swelling, the number of positive nodes (OR 1.2) and the number of overseas
      flights (OR 1.4) was also significant, whereas for clinical lymphoedema age (OR
      1.07) was significant. We conclude that domestic air travel (<4.5 h) is low risk
      and that compression devices are possibly counterproductive.

PMID- 14965649
TI  - Factors influencing cosmetic results after breast conserving management (Turkish
      experience).
AB  - We aimed to determine predictive factors affecting cosmetic results after breast
      conserving management in breast cancer. Data on 96 patients with 97 breast cancer
      cases, who had been admitted to Uludag University M.A. Radiotherapy Center
      between October 1995 and December 1998 and managed with breast-conserving
      treatment, were analysed to determine the factors affecting cosmetic outcome.
      Possible factors affecting cosmesis were grouped as patient-related, tumor
      related and treatment-related. Mann-Whitney U test was used in univariate
      analyses whereas logistic regression was used in multivariate analyses. Median
      follow-up time was 29.5 months ranging between 11 and 53 months and median age at
      admission was 50 (range 22-84). Cosmetic results were grouped in five categories;
      excellent; good; fair; poor and, very poor, using criteria, such as presence of
      fibrosis, telangiectasia, shape of breast, asymmetry, status of areola,
      pigmentation. Treated breasts were scored by the patients, three radiation
      oncologists and a breast surgeon independently. In the analysis performed using
      scores given by the patients, cases with scores 3 and above (unsatisfactory) were
      compared with cases with scores below 3 (satisfactory). Eighty-two patients (84%)
      considered cosmetic result as satisfactory (excellent/good) whereas 15 patients
      (16%) considered unsatisfactory (fair/poor/very poor). In univariate analysis
      using Mann-Whitney U test, type of surgery (P=0.0655) was the statistically
      significant factors affecting cosmetic results. In multivariate analysis using
      logistic regression, tumor quadrant (P=0.0060) and elapsed radiation therapy days
      (P=0.0090) were the most significant factors. Median values were taken into
      consideration for the scores given by the physicians and cases with scores 3 and
      above (unsatisfactory) were compared with cases with scores below 3
      (satisfactory). Eighty-two cases were evaluated as satisfactory (84%) whereas 15
      cases were unsatisfactory (16%). In this set of data, patient age (P=0.0144),
      menopausal status (P=0.0111), institution which surgery was performed (P=0.0045),
      type of surgery (P=0.0044), placement of metallic clips (P=0.0083) and skin
      fibrosis (P=0.038) were found to be significant in univariate analysis using Mann
      Whitney U test. In multivariate analysis using logistic regression, institution
      where surgery took place (P=0.0015), menopausal status (P=0.0087) and
      telangiectasia (P=0.0657) were the most significant factors.

PMID- 14965650
TI  - The psychological impact of post-operative arm morbidity following axillary
      surgery for breast cancer: a critical review.
AB  - In this paper we review the published research that has investigated the
      psychological impact of arm morbidity associated with axillary dissection for
      early breast cancer. This critique is particularly timely given the drive towards
      minimally invasive techniques, such as sentinel node biopsy, which aim to reduce
      the incidence and severity of post-operative arm problems. Reported symptoms are
      multifactorial and include numbness, pain, swelling, weakness/stiffness, and
      restricted shoulder mobility of the affected arm. Conclusions from the few
      studies that have investigated the severity, incidence, duration and
      psychological impact of such disability are often limited by methodological
      problems. We identify these limitations and examine assessment tools used to
      determine the psychological impact of lymphoedema. The paper highlights the need
      for methodological rigor in study design, and the careful selection of
      appropriate, sensitive, reliable and clinically meaningful outcome measures to
      evaluate the impact of post-operative arm morbidity.

PMID- 14965651
TI  - Is lactation mastitis and shooting breast pain experienced by women during
      lactation caused by Candida albicans?
AB  - The evidence relating Candida albicans with deep breast pain suffered by some
      women during breast feeding is reviewed. There is little direct evidence to
      support the aetiological role of Candida albicans in this condition, and
      therefore the prescription of fluconazole (an antifungal drug) to lactating women
      with deep breast pain as suggested by a number of authors of studies on this
      subject cannot be justified unless as part of a clinical trial.

PMID- 14965652
TI  - A case of melioidosis of the breast present at screening mammography.
AB  - A previously well 54-year-old woman presented for screening mammography with a 3
      day history of an inflamed lump in her right breast. She was subsequently
      admitted to hospital with acute melioidosis where right breast abscesses were
      drained. Following recovery and discharge, she was reviewed at the mammographic
      screening unit where her previous abnormal mammogram was found to be due to
      melioidosis. To our knowledge this is the first reported case of melioidosis of
      the breast and its appearance on mammography and ultrasound are described.

PMID- 14965653
TI  - A prospective audit of the use of a buttress suture to reduce seroma formation
      following axillary node dissection without drains.
AB  - A prospective audit of seroma formation following breast-conserving surgery for
      carcinoma with axillary dissection was carried out. Ninety-seven consecutive
      patients were studied. The post-operative formation of fluid within the axilla
      (seroma) was recorded on a computerised data collection system. From August 1998
      to December 1998, no drain or other axillary restriction was used. The seroma
      rate in 27 of these patients who had at least seven nodes in the axillary sample
      was 14/27 (52%). From December 1998 to June 1999, an additional suture was
      inserted between the axillary skin and the chest wall (buttress suture). This was
      designed to obliterate the axillary space after dissection. There were 37
      patients with seven or more nodes in the axillary dissection in this study and of
      these, nine patients developed a seroma (24%) (P=0.007). The use of the buttress
      suture reduces the seroma rate following axillary dissection without axillary
      drainage.

PMID- 14965654
TI  - Mitoxantrone and methotrexate chemotherapy with and without mitomycin C in the
      regional treatment of locally advanced breast cancer.
AB  - Fifty patients with locally advanced breast cancer received regional chemotherapy
      delivered angiographically via the internal mammary artery and varying vessels
      supplying the lateral aspect of the breast. Thirty three patients received
      mitomycin C, methotrexate and mitoxantrone, and 17 patients received methotrexate
      and mitoxantrone only. There was no significant difference in clinical response
      between the two groups. However, in patients who received mitomycin C, severe
      local skin toxicity occurred in nine patients resulting in delay of further
      therapy and considerable morbidity. Mitomycin C should not be administered
      regionally in patients with locally advanced breast cancer.

PMID- 14965655
TI  - Imaging features of breast trauma: a pictorial review.
AB  - Accidental injury to the female breast can cause symptoms and signs which may
      mimic carcinoma and can also be painful or disfiguring. Nine women who sustained
      injury to the breast are presented, illustrating some of the manifestations of
      traumatic injury to the female breast, the majority of which are attributable to
      fat necrosis. A brief discussion of the clinical and imaging features of fat
      necrosis is included. These cases reinforce the importance of triple assessment
      in any woman presenting with a breast lump, even with a clear history of trauma.

PMID- 14965656
TI  - Breast cancer screening: using familiality for earlier detection.
AB  - It is the purpose of this study to investigate whether breast cancer in patients
      with a positive family history is detected at an earlier stage with better
      prognostic markers than breast cancer in patients without a positive family
      history. In 481 patients, tumour size, tumour type, lymph vessel invasion, blood
      vessel invasion, receptor state, lymphatic spread, mitotic activity index (MAI)
      and survival were measured and compared, according to their family history. No
      difference was found between patients without a family history, patients with
      first-degree relatives or patients with second-degree relatives with breast
      cancer. Tumours were detected in the same stages and prognostic factors, MAI and
      survival were similar in all groups. A positive family history of breast cancer
      does not lead to earlier detection of breast cancer or a better survival.

PMID- 14965657
TI  - The sensitivity of the assessment process in screening mammography.
AB  - A follow-up of 3143 women from four screening centres, who were assessed after
      screening mammography, showed that 371 had breast cancer diagnosed at that
      assessment and 62 developed a breast cancer in the following 6 years. Of these,
      32 were judged to be false-negatives at assessment, with 23 of the 32 at the site
      originally suspected. The results show that the assessment process is not
      infallible and that the scale of the problem only becomes clear when an
      exhaustive search is made for missed cancers.

PMID- 14965658
TI  - The comparative sensitivity of mammography and ultrasound in women with breast
      symptoms: an age-specific analysis.
AB  - Despite its importance for clinical policy, there is little research on the age
      at which ultrasound or mammography is the preferred initial diagnostic test in
      women with breast symptoms. We analysed data from a series of 3799 consecutively
      presenting cancers. The overall sensitivity was 77.6% for mammography and 80.5%
      for ultrasound. Sensitivity increased with age in both mammography and
      ultrasound, though more steeply for mammography. In the 975 women who had both
      tests, ultrasound had a higher sensitivity than mammography in women younger than
      62 years of age, whereas mammography had a higher sensitivity than ultrasound in
      women older than 62 years. However, if the test results of the 2393 women who had
      mammography only are compared with the ultrasound results of the 975 women who
      had both tests, the 'cross-over' age at which the sensitivity of the two tests is
      equal occurs at the earlier age of 48 years. The presence of a palpable finding
      increases the sensitivity of ultrasound but does not influence the sensitivity of
      mammography.

PMID- 14965659
TI  - An analysis of factors associated with interval as opposed to screen-detected
      breast cancers, including hormone therapy and mammographic density.
AB  - A comparison of 270 interval breast cancers in South Australian women aged 50
      years and over with 628 age-matched screen-detected cases indicated that the
      former had more advanced stages (P<0.001), higher grades (P<0.001), and more
      frequently a history of past breast problems (P<0.027). After adjusting for these
      factors, and presence of a self-reported breast lump at the last screen, using
      conditional logistic regression, hormone replacement therapy (HRT) exposure in
      the 6 months prior to this screen had a raised relative odds (95% CL) of an
      interval cancer of 1.48 (1.02, 2.14). For 479 women where breast density was
      measured, high density showed an elevated relative odds of an interval cancer of
      2.62 (1.71, 4.02). The relative odds of a high density was raised to 2.02 (1.33,
      3.06) when the HRT history was positive. Screeners should be aware when there is
      a history of HRT or past breast problems, or a high breast density, that there is
      an increased probability of a subsequent interval cancer.

PMID- 14965660
TI  - An approach for high sensitivity detection of breast cancer by analysis of
      changes in structure of the cytoplasmic matrix of lymphocytes specifically
      induced by a specific breast tumour antigen (MUC-l/SEC).
AB  - An alternative procedure for detection breast cancer was examined based on the
      observation that lymphocytes re-exposed in vitro to antigenic stimulation will
      change their intracellular structuredness as measured by polarization of
      fluorescent light emitted by fluorescein labeled cells (SCM test). The specific
      antigen MUC-l/SEC was used to elicit such response in lymphocytes of patients
      with and without breast cancer. Eighty-five samples with breast cancer were
      tested, of which 72 were correctly diagnosed. Of the 41 controls, 35 were
      correctly identified as healthy subjects. The sensitivity of the test was 85% and
      the specificity was 81%. These results suggest a possible valuable method for
      screening and early detection of breast cancer. The clinical importance of this
      procedure lies in the ability to screen high-risk populations with higher
      specificity and sensitivity than any combinations of currently available
      procedures for breast cancer detection.

PMID- 14965661
TI  - Ultrasonic specimen radiography for non-palpable breast lesions.
AB  - A retrospective review of ultrasound guided breast excisional biopsies performed
      in a Surgical Unit of Princess Alexandra Hospital in 1998-99 was undertaken to
      assess the use of ultrasound specimen radiography. In this series a total of 55
      localization biopsies were performed for impalpable lesions in 53 women. In 21
      patients (38%), specimen ultrasound was used to confirm that the lesion in
      question had been excised, whereas for 34 lesions (62%), specimen X-ray was
      undertaken. In a total of six cases (10.9% overall) the radiographic abnormality
      was seen on ultrasound only. Real-time specimen sonography is a technique which
      is very appropriately utilized in conjunction with ultrasound guided excisions
      and can be easily performed either in the radiology department or the operative
      suite with minimal time delay. It could have particular application for lesions
      that are detected in younger women with dense breast parenchyma. The results of
      this review confirm specimen sonography to be a reliable technique.

PMID- 14965662
TI  - Pre-operative prediction of invasive vs intraductal breast cancer type:
      multivariate analysis of the accuracy of clinical and imaging findings.
AB  - Two consecutive series of 107 invasive carcinomas and 108 carcinomas in situ of
      the breast were considered retrospectively. The main symptomatic, clinical and
      cytological features were retrieved from clinical records, whereas the features
      at mammography and/or ultrasonography were reclassified at a blinded review by an
      expert radiologist. The power of predicting invasion on the basis of these
      features was then evaluated. The accuracy of such a prediction was compared to
      that of a mathematical model using the same diagnostic features by multivariate
      logistic regression analysis. Neither approach reached a satisfactory accuracy,
      but the radiologist's judgment (sensitivity 97.1%, specificity 81.9%, positive
      predictive value 98.4%, negative predictive value 71.6%, overall accuracy 95.8%)
      was slightly superior to the mathematical model (sensitivity 93.2%, specificity
      87.9% positive predictive value 98.8%, negative predictive value 53.7%, overall
      accuracy 92.8%). Although some presentations are significantly associated with
      invasive or in situ status, diagnostic features alone are not sufficiently
      accurate to bypass histological confirmation, although they might give useful
      clinical indications.

PMID- 14965663
TI  - Immediate reconstruction in breast cancer surgery requires intensive post
      operative pain treatment but the effects of axillary dissection may be more
      predictive of chronic pain.
AB  - The aim of this study was to investigate post-operative pain intensity, analgesic
      consumption and the incidence of chronic pain in women after different types of
      breast cancer surgery. Patients were randomized to either patient-controlled
      analgesia or nurse-administered analgesia. Opioid-consumption was registered for
      24 h. A division of the patient-material into four subgroups was performed: (1)
      mastectomy; (2) mastectomy and axillary lymph node dissection; (3) mastectomy and
      reconstruction; and (4) mastectomy, reconstruction and axillary lymph node
      dissection. Visual analogue scale was used to measure pain intensity. Four years
      after surgery, a questionnaire regarding persistent pain was completed. Patients
      undergoing reconstruction scored higher pain levels than the others. Patient
      controlled analgesia provided better pain relief but also considerably higher
      consumption of opioids by the women who underwent breast reconstruction. The
      incidence of remaining pain was 25% after 3-4 years. Immediate breast
      reconstruction causes severe post-operative pain that can respond poorly to
      opioids. Chronic pain after breast cancer surgery is common and should be further
      analysed aiming at better prevention and treatment options.

PMID- 14965664
TI  - The value of follow-up of patients with early breast cancer treated with
      conservative surgery and radiation therapy.
AB  - A retrospective study of 438 women with Stage I or II breast cancer who were
      treated with conservation therapy and followed in accordance with a 'minimal'
      follow-up programme was conducted to identify a follow-up schedule to optimize
      detection of salvageable recurrence and/or contralateral new primary breast
      cancer, and to rationalize cost. Data from 104 women were used to establish the
      cost of detecting a salvageable event and to model the efficacy of 13 theoretical
      follow-up schedules. Among women followed for 5 years, 21% relapsed, and 19% of
      recurrences were salvageable. Only 0.1% of 1294 follow-up visits resulted in the
      detection of a salvageable event, at an average cost per woman of A $802. A
      simulated follow-up programme involving monthly visits for 5 years, costing A
      $3870 per woman, was the most successful in facilitating the detection of a
      salvageable recurrence but was also prohibitively expensive. Three-monthly visits
      for 4 years and 12-monthly for 1 year was more efficacious, but a better
      understanding of the psychosocial impact and patients' preferences for follow-up
      is required before any programme is implemented.

PMID- 14965665
TI  - A double-blind randomized controlled trial of isoflavones in the treatment of
      cyclical mastalgia.
AB  - Cyclical mastalgia is very common in Western populations and is believed to have
      an hormonal basis. Simple measures such as vitamins or evening primrose oil are
      not very effective, yet the disease rarely warrants anti-oestrogen therapies.
      Isoflavones are a subgroup of phytoestrogens which we hypothesized might be a
      simple and effective means of therapy as they act as a weak anti-oestrogen in pre
      menopausal women and have no side-effects. A double-blind randomized control
      trial of either placebo, 40 mg or 80 mg of isoflavones was undertaken after an
      initial 2 month single-blind 'Placebo Lead-in' to exclude women with a
      significant placebo response. Eighteen women were randomized to the treatment
      phase of the trial. Nine of the 12 women on treatment had a worthwhile
      improvement in their pain compared to only two of six on placebo. The reduction
      in pain was 13% for placebo, 44% for 40 mg of isoflavone per day and 31% for 80
      mg per day. There have been no previous clinical studies of isoflavones for the
      treatment of mastalgia and the benefit demonstrated in this study adds another
      valuable arm to therapy.

PMID- 14965666
TI  - Gigantomastia unrelated to pregnancy or puberty: a case report.
AB  - Idiopathic gigantomastia occurs during puberty and pregnancy but a spontaneous
      case has not been reported in the literature. An unusual case is described, which
      required urgent bilateral mastectomy to control systemic sepsis and extreme
      discomfort.

PMID- 14965667
TI  - Areolar discharge and peri-areolar breast cysts in adolescent females.
AB  - Nipple discharge in adolescents is well documented, and usually results from
      endocrine dysfunction or local breast disease. Areolar discharge, however, in
      healthy adolescent girls is a rare finding, and is sometimes associated with peri
      areolar lumps. These patients usually present with painless discharge from around
      the nipple, and sometimes with a lump at the site. Some patients present with a
      lump only, and secondary inflammation at the site can occur. Although the lesions
      often resolve spontaneously, they can recur, and the treatment options are
      discussed. There are very few cases in the literature of areolar discharge in
      young girls, which perhaps reflects its incidence. The following case report of
      16 patients appears to be the largest collection of patients reported with this
      apparently benign condition. Ultrasound examination is a useful tool in the
      diagnosis of this condition. Fine needle aspiration was sometimes curative, but
      surgical excision appeared definitive therapy.

PMID- 14965668
TI  - Breast cancer screening--time to move forward.

PMID- 14965669
TI  - The proven reliability of mammography screening.

PMID- 14965670
TI  - Evidence relevant to the investigation of breast symptoms: the triple test.
AB  - This paper reviews and summarises evidence on the investigation of breast
      symptoms based on triple testing. The triple test (where any component is
      positive) has a sensitivity of 99.6%, a specificity of 62%, a likelihood ratio of
      2.62 for a positive result, and a likelihood ratio of 0.006 for a negative
      result. We present measures of test accuracy for the components of the triple
      test that allow easy estimation of the probability of breast cancer in
      symptomatic women, given any possible combination of results.

PMID- 14965671
TI  - Tumour location and prognostic characteristics as determinants of survival of
      women with invasive breast cancer: South Australian hospital-based cancer
      registries, 1987-1998.
AB  - Survivals from breast cancer varied by location of lesion (P<0.001), with 10-year
      survivals of 61% applying for central (n=772), 73% for medial (n=350), and 72%
      for lateral (n=966) lesions. Univariate analyses of determinants of central
      locations indicated that the following were predictive: a more advanced TNM stage
      (P<0.001); a larger tumour diameter (P=0.002); a higher grade (P=0.032); a
      negative oestrogen receptor status (P=0.004); a negative progesterone receptor
      status (P=0.004); and histological type (P=0.011), with more of the lobular
      lesions being located centrally. Cox proportional hazards regression indicated
      that the relative risk (95% confidence limits) of case fatality for central, as
      opposed to other, lesions reduced from 1.46 (1.20, 1.78) to 1.16 (0.95, 1.41)
      when stage was added to the model, with no other factor having an additional
      conditioning effect. It is concluded that central lesions have worse outcomes,
      mostly due to their more advanced stages. Means of finding these tumours earlier
      should be investigated.

PMID- 14965672
TI  - Surveillance mammography after treatment of primary breast cancer: a systematic
      review.
AB  - As the prevalence of diagnosed breast cancer increases, it is important to define
      how best to provide long-term follow-up. Whereas many aspects of follow-up remain
      controversial, guidelines recommend surveillance mammograms as the only
      investigation to be performed routinely. We conducted a systematic review of the
      literature to elucidate the effect of routine surveillance mammograms on
      detecting ipsilateral recurrence (IR) and contralateral breast cancers (CBC). The
      systematic review yielded 15 articles. All were observational studies and ranked
      as level II-2 or III evidence. There were no randomized controlled trials
      identified. Most of the ten studies on detection of IR did not report on outcomes
      after detection. When reported, most studies found that the method of detection
      of IR did not influence overall survival or disease-free survival. Two of the
      nine studies on detection of CBC found that the CBC was detected at an earlier
      stage than the initial breast cancer, but did not report on long-term outcomes.
      This systematic review highlights the need for further research to help better
      define the optimum surveillance mammography regimen.

PMID- 14965673
TI  - The role of lymph node sampling and radiotherapy in the management of the axilla
      in early breast cancer.
AB  - Management of the axilla in early breast cancer is an issue of ongoing debate. We
      reviewed our experience in 312 patients who underwent axillary lymph node
      sampling between 1994 and 1998, of whom 81 patients (24%) had axillary lymph node
      metastasis. There have been two axillary recurrences, one associated with local
      recurrence to the breast and one presenting with distant metastasis. There were
      no patients with isolated axillary disease as their only site of recurrence and
      no axillary failures in the node-positive group treated with axillary sampling
      and radiotherapy. Axillary lymph node sampling effectively stages the axilla.
      This can safely be followed by radiotherapy to the axilla in case of lymph node
      metastasis. Axillary lymph node sampling forms a sound basis to develop new
      techniques, such as sentinel lymph node biopsy currently investigated by ongoing
      trials.

PMID- 14965674
TI  - Evaluation of immediate versus delayed shoulder exercises after breast cancer
      surgery including lymph node dissection--a randomised controlled trial.
AB  - Two hundred and thirty women who had undergone surgery for breast cancer were
      randomised to a prospective study, comparing early (group A) and delayed (group
      B) shoulder exercise. Preoperatively, group A received instructions and an
      exercise programme supervised by a physiotherapist, whereas group B received
      written instructions to use the arm normally but to avoid heavy work. Two weeks
      after surgery both groups were given identical exercise programmes. Shoulder
      mobility, hand strength and arm volume were measured preoperatively, 1 month, 6
      months and 2 years postoperatively. After 2 years 13.8% of the women had
      lymphoedema, but there were no significant differences between the groups. Grip
      strength was slightly decreased during the postoperative period in both groups
      (n.s.). Postoperatively, all movements in both groups were decreased after 2
      weeks and 1 month and shoulder elevation and abduction remained decreased at 2
      years. Mobility in group A recovered significantly earlier than in group B.

PMID- 14965675
TI  - Occult lymph node metastases in patients with 'node negative' breast carcinoma
      treated with conservation surgery and axillary node sample and who subsequently
      developed axillary recurrence.
AB  - We examined axillary lymph nodes from 26 patients with node-negative breast
      cancer managed by axillary node sampling and no further axillary treatment, but
      who subsequently developed axillary recurrence after a mean follow-up of 7 years
      to determine the incidence of micrometastatic disease in these patients. Twenty
      six matched controls with an identical length of follow-up who were node-negative
      on an axillary node sample, but have not developed axillary recurrence, also
      underwent node examination and the incidence of metastases in the two groups were
      compared. Lymph nodes were sectioned at two additional levels 100 microm apart.
      Sections at each level were stained with haematoxylin and eosin (H&E) and
      antibodies to PanCK and MUC1 protein. The original H&E section from each node was
      reviewed and additional sections from each lymph node were examined by a
      pathologist who was blinded to outcome. Review of the original H&E sections of
      the nodes revealed metastases that had been overlooked at the time of diagnosis
      in two (8%) patients from the recurrence group. A further two (8%) patients from
      the recurrence group and three (12%) from the control group had axillary nodes
      which contained micrometastases. Immunocytochemistry was important in identifying
      all micrometastases. There was no significant difference in the incidence of
      axillary node micrometastases between patients with and without axillary node
      recurrence. Although the number of cases was small, this study suggests that
      axillary recurrence following a negative sampling procedure is not commonly due
      to missed axillary node metastases.

PMID- 14965676
TI  - MIB-1 assessments in breast cancers.
AB  - The variability of MIB-1 measurements in breast cancer was assessed in
      histological sections from core and excision biopsies taken simultaneously in 13
      cases and sequentially (with an intervening period of 2-3 weeks) in 17 cases.
      Results showed no significant differences in values between cores and sections,
      whether taken simultaneously or sequentially. Individual pairs of cores and
      sections occasionally demonstrated substantial differences. The mean ratio of MIB
      1 scores between cores and sections was 0.97 [95% confidence interval (CI)=0.68
      1.38]. However 95% confidence intervals for ratios within individuals were 0.14
      6.68. Although the two samples can be equivalent on an average over numerous
      patients, they cannot be taken as equivalent within individuals. Severe
      heterogeneity complicates the assessment of MIB-1 in individual breast cancers
      and limits utility in monitoring changes in proliferation with treatment.

PMID- 14965677
TI  - Follow-up in women with breast cancer: the patients' perspective.
AB  - We surveyed the opinions of patients on routine follow-up for early breast cancer
      to assess their satisfaction with current breast cancer follow-up arrangements,
      establish the issues that are important to patients in this setting and to assess
      their opinions on different models of care in breast cancer follow-up. A self
      completion questionnaire was issued to 134 women attending an outpatient breast
      cancer follow-up clinic at a central teaching hospital in Glasgow. Most women
      (84%) considered follow-up 'important' and 90% were satisfied with current follow
      up practice. Almost all patients (91%) were content with both the current
      frequency and duration of their appointments. Risk of recurrence and effects of
      treatment were considered the most important topics for discussion. Two-thirds of
      patients felt it was important to see the same member of staff at each follow-up
      appointment. The majority (64%) would have been satisfied with a nurse-led system
      of follow-up, whereas only 38% would be happy with General Practitioner-led care.
      Although patients are generally satisfied with current follow-up arrangements,
      most would accept the involvement of specialist nurses in conjunction with a
      consultant.

PMID- 14965678
TI  - Impact of the '2 week wait' on referrals to breast units in the UK.
AB  - Thirty six per cent of women with breast cancer were not identified as requiring
      an urgent clinic appointment by their general practitioner. In contrast, large
      numbers of women with benign disease are graded as urgent by their general
      practitioner. Classification of patients with breast symptoms requiring hospital
      referral by general practitioner does not accurately differentiate between women
      with benign and malignant breast disease.

PMID- 14965679
TI  - A UK survey of tamoxifen prescribing and oestrogen receptor status.

PMID- 14965680
TI  - Mammographic axillary node calcification caused by metastatic breast carcinoma.

PMID- 14965681
TI  - Burn injuries after latissimus dorsi breast reconstruction in a cold climate.
AB  - The transposed and 'native' skin of a reconstructed breast using autogenous
      tissue transfer has impaired sensation. Two cases of thermal injury following
      latissimus dorsi breast reconstruction are reported. Both cases were due to the
      overnight application of a hot-water bottle to the reconstructed breast. We
      suggest that all patients should be warned of this potential complication
      especially in cold climates.

PMID- 14965682
TI  - Is massage following dye injection necessary in sentinel node biopsy in breast
      cancer?
AB  - In sentinel node biopsy of breast cancer, massaging of the dye injection site
      following subdermal injection of blue dye does not improve sentinel node
      detection rate or the time needed for sentinel node biopsy. It may reduce the
      number of false negative sentinel nodes.

PMID- 14965683
TI  - Molecular markers in breast cancer: can we use c-erbB-2, p53, bcl-2 and bax gene
      expression as prognostic factors?
AB  - We examined the prognostic value of c-erbB-2, p53, bcl-2 and bax overexpression
      in breast cancer. Immunostaining for c-erbB-2, p53, bcl-2 and bax gene expression
      was performed on 121 paraffin-embedded specimens of Stage I, II and III breast
      cancer patients diagnosed and treated in Hippokration Hospital, Athens Medical
      School, between 1986 and 1992. The primary tumor from 27 (24.1%), 69 (59%), 18
      (15%) and 63 (53.4%) patients stained positively for c-erbB-2, p53, bcl-2 and bax
      gene expression, respectively. Significant correlations were found between bax
      overexpression and age (P=0.04), tumor size (P=0.02) and disease stage (P=0.001),
      while no other significant associations were found between other molecular
      markers and clinical or histological parameters. None of the individual molecular
      markers examined proved to be independent prognostic factor for patients with
      breast carcinoma. C-erbB-2, p53, bcl-2 and bax genes have limited prognostic
      value. An approach that combines several molecular markers with established
      clinicopathological criteria may help physicians make more accurate predictions
      of prognosis in patients with breast cancer.

PMID- 14965684
TI  - c-erbB 2 serum level as prognostic factor in hormonally treated advanced breast
      cancer patients.
AB  - To investigate whether c-erbB 2 serum levels may be predictive of clinical
      response, progression-free and overall survival in postmenopausal women with
      advanced breast cancer hormonally treated, 265 patients enrolled in previous
      clinical trials were evaluated. C-erbB 2 serum levels were assessed before the
      start of treatment and in a subgroup of patients also at the first response
      evaluation. In addition, serum CA 15.3 levels were determined. The role of c-erbB
      2 was investigated by means of multiple regression models in which both c-erbB 2
      and CA 15.3 values were modelled as continuous variables together with other
      known prognostic factors. The failure probability tended to be higher in the
      presence of high c-erbB 2 levels, but the trend was not statistically
      significant; in contrast, significant results were obtained for progression-free
      survival (PFS,P <0.001) and overall survival (OS, P=0.014). The within-patient c
      erbB 2 variation significantly predicted PFS (P=0.006) and OS (P=0.040). It is
      worth noting that c-erbB 2 and CA 15.3 baseline levels were significantly
      correlated and that the prognostic effect of c-erbB 2 tended to disappear in the
      presence of high CA 15.3 levels for PFS and OS.

PMID- 14965685
TI  - Expression of estrogen receptors (alpha, beta) and insulin-like growth factor-I
      in breast tissue from surgically postmenopausal cynomolgus macaques after long
      term treatment with HRT and tamoxifen.
AB  - The novel estrogen receptor ERbeta could be a key factor for proliferation and
      breast cancer risk. In a primate model for long-term HRT, surgically
      postmenopausal cynomolgus macaques were treated for 35 months with conjugated
      equine estrogens (CEE), medroxyprogesterone acetate (MPA), CEE+MPA and tamoxifen
      (n=5 in all groups). The immunohistochemical expression of ERalpha, ERbeta and
      IGF-I in breast tissue was quantified by image analysis. Overall the levels of
      ERbeta were higher than for ERalpha. In untreated animals, the median area of
      positive cells was 58% and 21%. The lowest levels for ERbeta were seen during
      treatment with CEE/MPA (3%) and in this group the expression of ERbeta was lower
      than for ERalpha. Tamoxifen had effects similar to estrogen. ERbeta may have a
      role to modulate the proliferative response following activation of ERalpha. The
      results suggest that hormonal treatments have a different influence on the
      balance ERbeta/ERalpha in breast tissue.

PMID- 14965686
TI  - Monitoring interval cancers in mammographic screening: the Florence District
      programme experience.
AB  - The aim of the present study was to monitor the occurrence of interval (breast)
      cancers (IC) as an interim outcome measure of quality assurance in the
      mammographic screening programme of the District of Florence. IC were identified
      by linking breast screening data with registrations of breast cancers from the
      Tuscany Tumour Registry. The main outcome measures were the numbers, rates, and
      the proportionate incidence of IC. Overall, 90 invasive IC were observed among
      women who attended the breast screening programme in the District of Florence
      from 1 January 1985 to 31 December 1993, respectively, 23, 50, on 17 cases, at 1,
      2, and 3 years after the last negative screening test. Expressed as a proportion
      of underlying incidence, the figures are 16, 44, and 46%. As to risk factors for
      IC, mammographic density was the most important one in the present survey,
      whereas no effect of age emerges from the present study.

PMID- 14965687
TI  - Granular cell tumor of the breast: a diagnostic pitfall.
AB  - We report a rare case of benign granular cell tumor of the breast associated with
      multiple similar lesions of the scalp, the right shoulder, the right flank, the
      abdominal wall and the vulva, treated with wide excisions.

PMID- 14965688
TI  - Fine needle aspiration cytology prior to breast ultrasonography does not alter
      ultrasound diagnostic accuracy or patient management.
AB  - INTRODUCTION: Fine needle aspiration cytology (FNAC) prior to serial sonographic
      (USS) examination of the breast is said to impede accurate diagnosis. This study
      aimed to test the effect of performing FNAC prior to USS in a one-stop
      symptomatic breast clinic. METHODS: All patients (n=368) attending a one-stop
      clinic over a 1-year period were stochastically allocated to imaging prior to
      (Group 1) or after (Group 2) clinical examination and FNAC. Additional procedures
      required for diagnosis (open or core biopsies), false negative USS grade and
      final outcome were recorded. Statistical analysis was performed using the
      Fisher's exact test. RESULTS: There was no statistical difference between the two
      groups. CONCLUSION: In the clinical setting of a one-stop visit, FNAC prior to
      breast USS does not alter ultrasound diagnostic accuracy or patient management.

PMID- 14965689
TI  - Quality of life profile: from measurement to clinical application.
AB  - Quality of life (QoL) can be assessed in an accurate, valid and reliable way by
      means of standardized QoL questionnaires and is an important endpoint in clinical
      trials today. The aim of this study is to implement quality of life as a
      diagnostic tool for problem-oriented follow-up care of cancer patients. This is
      done in the framework of an intervention study in the area of regional health
      care research using qualitative analysis and the methodological concept of
      barrier analysis. We developed the diagnostic tool by generating individual,
      graphic QoL profiles based on patients' responses to the EORTC QLQ-C30 and the
      corresponding disease-specific modules BR23 for breast cancer and CR38 for rectal
      cancer. The clinical application is investigated by assessing physicians'
      responses. The QoL profile is judged as a useful diagnostic tool by all
      participating physicians. It enables physicians to assess the QoL of the patient
      and incorporate the knowledge they gain in their daily practice. Especially in
      breast cancer follow-up care QoL profiles give added value to both patients and
      doctors. The next implementation steps have to extend the concept of QoL to
      larger groups of patients and physicians by overcoming the restraining factors as
      identified in the barrier analysis.

PMID- 14965690
TI  - Morbidity of tamoxifen-perceptions of patients and healthcare professionals.
AB  - There is little published data comparing patients' and doctors' perceptions of
      tamoxifen-related morbidity and toxicity, in particular in terms of side-effects
      which are not medically serious but which disrupt quality of life. We undertook a
      questionnaire-based study of 210 randomly selected, disease-free pre- and post
      menopausal breast cancer patients to assess perceived morbidity whilst taking
      tamoxifen. We also questioned 143 healthcare professionals, including nurses, GPs
      and oncologists, on their opinions of tamoxifen-related side-effects. This study
      suggests that patients experience significant morbidity while taking adjuvant
      tamoxifen but will tolerate this for the sake of anticipated benefits. Healthcare
      professionals particularly hospital-based doctors and specialist nurses tend to
      overestimate the prevalence and severity of tamoxifen-associated symptoms.

PMID- 14965691
TI  - Breast cancer in the inframammary fold: is preserving the inframammary fold
      during mastectomy justified?
AB  - INTRODUCTION: Preservation of the inframammary fold (IMF) during mastectomy
      facilitates breast reconstruction. The true incidence of breast cancer in the IMF
      is not well known. We report our experience of this condition. METHODS: The site
      and clinical features of initial presentation and recurrence of breast cancer
      within the breast in a consecutive series of 580 patients between 1997 and 2000
      was studied. RESULTS: Primary breast tumours were detected within the IMF in four
      patients (0.7%). Only two tumours presenting within the IMF were visible on
      mammography. During the follow-up period, there were five patients with local
      recurrences involving either breast or skin flaps, but no breast cancer
      recurrence was observed in the IMF. CONCLUSION: Tumours within the IMF are rare
      but its occasional occurrence requires reconsideration of the safety of
      preserving the IMF at mastectomy.

PMID- 14965692
TI  - Experience with sentinel node localisation in a district general hospital breast
      unit.
AB  - Intraoperative lymphatic mapping with identification of the first draining lymph
      node (sentinel node) is under investigation as a possible sole axillary staging
      procedure in breast cancer patients. The role of sentinel node biopsy in the
      district general hospital breast unit is currently unclear. We report a series of
      122 patients undergoing sentinel node biopsy, using a blue dye technique. The
      sentinel node was identified in 113 patients, and accurately predicted the status
      of the axilla in 108 patients (96%). Of 39 patients who were node positive, the
      sentinel node was the only positive node in 11 cases (26%). There were five false
      negatives in patients who had a node-positive axilla. We therefore suggest that
      sentinel node biopsy may be a feasible alternative to formal axillary dissection
      in certain patients, and that lack of access to radioisotope facilities in a
      district general hospital need not preclude such an approach.

PMID- 14965693
TI  - Breast tuberculosis.
AB  - Breast tuberculosis is a rare form of tuberculosis. Of all the breast diseases
      treated surgically, tuberculosis is seen in the range between 0.025% and 0.1%.
      This ratio is higher in undeveloped countries. We presented five cases with
      breast tuberculosis. Their ages were between 20 and 63 years. All of them had
      children and were breastfeeding. The cause of admission to the hospital was
      swelling in four of them and pain in the remainder. All of the lesions were
      unilateral. One case had received antituberculosis treatment for pulmonary
      tuberculosis 10 years ago. AAFB was not detected in sputum, breast discharge,
      urine and tissue culture in all the cases. Diagnosis was made histopathologically
      from the excisional biopsy material. Caseating granulomatosis was also found in
      axillary lymph nodes in three cases. Antituberculosis therapy was planned as
      2HRZE/4HR for all of the cases. Three of them completed the therapy without any
      complaints. One case left the hospital without permission. The last one is now
      undergoing resistant tuberculosis treatment for pulmonary disease without any
      complaint of her breast. As a conclusion, although tuberculosis of breast is
      extremely rare, it should be kept in mind particularly in developing and
      undeveloped countries.

PMID- 14965694
TI  - An unusual case of metastatic post-irradiation breast sarcoma.
AB  - A 71-year-old lady developed a left breast angiosarcoma 10 years after a wide
      local excision and external beam radiotherapy for invasive breast cancer. Three
      years after a left simple mastectomy for the angiosarcoma, she presented with
      metastatic angiosarcoma in the contralateral axilla. There were no local or
      distant metastases. This is the first reported case of isolated contralateral
      axillary metastases from post-irradiation angiosarcoma of the breast. A previous
      study has reported ipsilateral axillary metastases in relation to secondary
      breast angiosarcoma. Contralateral axillary metastases have always been
      associated with extensive distant metastases. We present a review of the
      available literature on radiation-associated breast angiosarcomas.

PMID- 14965695
TI  - Uterine metastasis from infiltrating ductal carcinoma of breast in a patient
      receiving tamoxifen.
AB  - The established relationship between tamoxifen and the development of endometrial
      cancer causes differential diagnostic problems between metastatic and primary
      uterine neoplasms. A 45-year-old woman underwent modified radical mastectomy
      because of left-breast cancer. She presented with abnormal vaginal bleeding 6
      years later, while still on tamoxifen therapy. The endometrial curettage revealed
      undifferentiated adenocarcinoma. She underwent total abdominal hysterectomy,
      bilateral salphingoopherectomy as well as pelvic and periaortic lymphadenectomy.
      Microscopic examination revealed neoplastic cells which formed sheets and duct
      like structures in the endometrium. The pattern was not that of a primary
      endometrial tumour and an immunohistochemical staining was performed using human
      breast gross cystic disease fluid protein-15 (GCDFP-15) which was found out to be
      positive in the tumour cells. A diagnosis of metastatic ductal carcinoma of the
      breast in the uterus was rendered. Uterine metastasis should be kept in mind in
      patients with a history of breast cancer who are on tamoxifen therapy.

PMID- 14965696
TI  - Breast hemangioma mimicking carcinoma.
AB  - Breast hemangiomas are rare, and usually appear as well-delimited round or oval
      nodules at mammography. We report a case of a woman with a breast hemangioma,
      which mammographic features simulated malignancy, and present its pathologic
      correlation. Hemangiomas are benign vascular tumors that are rarely present in
      the breast, usually found incidentally on microscopy of biopsy material for
      other. They are occasionally detected by mammography, presenting as well
      delimited round, lobulated nodules, sometimes with calcifications. We present the
      mammographic findings and pathologic correlation in a case of breast hemangioma
      with an atypical radiological manifestation, simulating a carcinoma. To our
      knowledge, this is the first reported case with these radiologic characteristics.

PMID- 14965697
TI  - Mucinous breast carcinoma.
AB  - A case of mucinous breast carcinoma is discussed in which several unusual
      features in presentation and difficulties in management are addressed.

PMID- 14965698
TI  - Limitations of fine needle aspiration cytology (FNAC) in the diagnosis of breast
      lesions.

PMID- 14965699
TI  - Assessment of the effects of breast cancer on bone and the response to therapy.
AB  - The skeleton is the most frequent site of metastatic disease in breast cancer and
      also the site of greatest morbidity. In addition, there is now recognition that
      accelerated bone loss associated with chemotherapy or hormonal therapy leads to
      an increased risk of osteoporosis in long-term breast cancer survivors. An
      improved range of treatment options is available and assessment of skeletal
      response both to the disease and to therapy is therefore of growing importance.
      Plain radiographs remain widely used to assess response, but are of limited
      sensitivity. The isotope bone scan is more sensitive, but lacks specificity.
      Computerised tomography, magnetic resonance imaging and positron emission
      tomography all have an increasing role. In treatment-induced osteoporosis, bone
      mineral density is now readily measured by DEXA scanning. Tumour markers such as
      CEA, CA 15-3, CA 549 and TPA may have a role in assessing response, but probably
      in combination rather than individually, using an appropriate quantitative model.
      Several trials have shown that bone markers, especially markers of bone
      resorption such as Ntx, Ctx, PYD and DPD, appear to have strong potential as
      rapid, convenient and inexpensive measures of response. There is also evidence
      that they may be used as predictive or prognostic indicators. Evidence is
      accumulating that the reduction of bone resorption markers into the normal range
      results in substantially reduced morbidity in metastatic breast cancer and that
      this should be a major target of therapy.

PMID- 14965700
TI  - Delay in the clinical diagnosis of breast cancer: estimating its effect on
      prognosis, with particular reference to medical litigation.
AB  - Medical malpractice litigation is increasing. Delay in diagnosis is the commonest
      basis for litigation involving the treatment of breast cancer. When delay in
      diagnosis has occurred, any losses for which a plaintiff seeks compensation
      require estimates to be made of any change in prognosis over the period of the
      delay relative to the extent of disease found when treatment is finally
      undertaken. We have examined the natural history of breast cancer and have
      attempted to provide evidence-based quantitative guidelines for the evaluation of
      the losses which may be claimed in malpractice cases.

PMID- 14965701
TI  - Breast papilloma: mammogram, ultrasound and MRI appearances.
AB  - Breast papilloma are difficult to diagnose by triple assessment. Their symptoms,
      clinical signs and radiological appearances are differing widely. In this paper,
      we report the symptoms and clinical signs of 35 patients with proven breast
      papilloma and consider the relative merits of mammography, ultrasound scans and
      magnetic resonance imaging in their assessment.

PMID- 14965702
TI  - The Internet: the future source of information for professionals in the field of
      breast cancer.

PMID- 14965703
TI  - Is a one-step operation for breast cancer patients presenting nipple discharge
      without palpable mass feasible?
AB  - Although spontaneous nipple discharge without mass is a common complaint, only
      about 5-15% of patients with nipple discharge have cancer. The standard
      preoperative evaluations, including mammography, physical examination,
      ultrasonography and squeezing cytology, do not provide enough definite data to
      make a decision for surgery. We have investigated whether preoperative
      intraductal aspiration cytology and galactography supply sufficient information
      about the location and nature of the lesion, and have carried out a one-step
      operative procedure by adding frozen section diagnosis during surgery. A
      retrospective review of Kaohsiung Medical University Hospital patients presenting
      symptoms of nonpalpable mass was conducted from January 1989 to June 2000. The
      medical charts, pathology and cytology reports, and imaging studies were
      reviewed. Of 487 patients with spontaneous nipple discharge, 190 with pathologic
      discharge had complete preoperative galactography and intraductal aspiration
      cytology, and 176 received surgery. Fourteen cases with negative cytology and
      normal galactography, who had not had an operation, did not develop cancer during
      an average 7 years follow-up. The diagnostic accuracy rates of 35 cancer patients
      using galactography and cytology were 91.4% and 88.6%, respectively, and 97.1% in
      combination, which is better than those of 141 patients with benign lesions
      (77.3% and 84.4%, and 90.0% in combination, P<0.05). The results show a 91.5%
      preoperative diagnostic accuracy rate in all patients with nipple discharge, and
      can be used to discuss the diagnosis with the patient during the preoperative
      period. All 35 cases with cancer received the one-step procedure under general
      anesthesia. Sixteen patients received mastectomies, and the other 19 cases had
      ductolobular resections, depending on their preoperative evaluations and frozen
      section in pathology. There were no false positives or false negatives in frozen
      section when comparing permanent histology and residual cancer in mastectomy
      specimens. There were no symptoms of recurrence in any of the patients who had
      undergone the two different procedures during 7 years of follow-up. In patients
      with spontaneous nipple discharge without palpable mass, the preoperative
      intraductal cytology and galactography were reliable methods to evaluate
      intraductal lesions. The one-step procedure will be selected for those patients
      if the frozen section is added. The ductolobular resection with an adequate
      surgical margin should be the first choice for those nonpalpable breast cancers
      with nipple discharge. Due to the limited number of breast cancer cases studied,
      more cases and a long follow-up period are necessary in future.

PMID- 14965704
TI  - Wire localization of non-palpable breast lesions: out of date?
AB  - AIMS: With the increasing use of screening mammography, more and more non
      palpable lesions are found. As less invasive techniques like core needle biopsy
      are introduced, we evaluated our experience with the well-known standard
      procedure of surgical excision after wire localization. METHODS: We
      retrospectively evaluated the results of 479 wire localizations for non-palpable
      breast lesions between 1992 and 1999 in 465 patients. Feasibility and reliability
      of the procedure and the incidence of complications are reported. RESULTS: The
      mean age of these patients was 57 years (range 22-81 years). The mammographic
      finding with the highest rate of malignancy was density combined with
      architectural distortion (72%). The removal of the lesion was radiologically
      confirmed in 93%; if the lesion appeared to be not removed, after 3 months
      mammography was repeated, in 14 patients a second localization procedure was done
      and in 10 patients still a malignancy was found. In 79%, the excision after
      initial fine-wire localization was irradical. Twenty-five patients developed a
      haematoma and five patients had a wound infection. The overall malignancy rate
      was 50%. With a mean follow-up of 18 months in 11 patients with a diagnosis of
      benign disease after an adequate procedure, still a malignancy was found at the
      original excision site. CONCLUSION: In selected cases, especially as a part of
      the therapeutic procedure in breast-conserving therapy, there will remain a place
      for wire localization and excision biopsy. However, we have to reconsider its
      place as a diagnostic procedure as the results of less invasive procedures are
      promising.

PMID- 14965705
TI  - Occult primary breast carcinoma presenting as axillary lymphadenopathy.
AB  - BACKGROUND: The objective of this study was to review the need for radiotherapy
      or not in patients with occult primary breast cancer presenting with axillary
      metastases treated with breast conservation usually with no surgery to the
      breast. METHODS: From 1975 to 2001, 58 patients were treated with axillary
      lymphadenopathy from a cryptic primary breast carcinoma. After clinical and
      radiological assessment, 29 patients retained a diagnosis of occult primary
      breast carcinoma. Clinical and pathological data were collected retrospectively
      on the 29 patients and survival was calculated from the date of initial diagnosis
      using the Kaplan-Meier method. The median follow-up was 44 months. RESULTS:
      Median age at diagnosis was 57 years (range 28-81 years). Sixteen patients had
      radiotherapy to the ipsilateral breast. Eleven patients received no local therapy
      to the ipsilateral breast and two patients had quadrantectomies which were
      negative for malignancy. Locoregional relapse occurred in 12.5% of patients who
      had received radiotherapy and 69% of those who had not received any radiotherapy
      (P=0.02). Fifty-seven per cent of patients having a local relapse were salvaged
      with further surgery. The eventual breast conservation rate was 93%. Patients who
      received radiotherapy to the breast had significantly improved relapse-free
      survival (HR=0.31; P=0.04) and local relapse-free survival (HR=0.09; P=0.004).
      There were no significant differences in overall survival between those patients
      who had breast irradiation and those who did not (HR 0.91; 95% CI 0.18-4.5).
      CONCLUSION: Occult primary carcinoma with axillary metastases can be treated
      successfully with breast preservation but radiotherapy to the breast is necessary
      to minimize the risk of locoregional recurrence.

PMID- 14965706
TI  - Adjuvant ovarian ablation vs CMF chemotherapy in premenopausal breast cancer
      patients: trial update and impact of immunohistochemical assessment of ER status.
AB  - This trial, initiated in 1980, examined the relative values of adjuvant ovarian
      ablation and chemotherapy comprising cyclophosphamide, methotrexate and 5
      fluorouracil (CMF) in premenopausal women with pathological stage II breast
      cancer. With median follow-up for patients still alive of 13.9 years, there is no
      difference in survival between women receiving ovarian ablation and CMF (hazard
      ratio 1.01; 95% CI: 0.74, 1.37). Tumour oestrogen receptor (ER) status was
      assessed at the time using biochemical ligand-binding assay and retrospectively
      by immunohistochemistry (IHC). Agreement between these two methods was only fair,
      but both confirmed the importance of ER status in determining appropriate
      adjuvant systemic therapy. A statistically significant interaction between IHC
      quick score and treatment (P=0.001) showed ovarian ablation was more beneficial
      for patients with a positive quick score, whereas women with a quick score of 0
      had a significantly higher risk of death with ovarian ablation (2.33; 95% CI:
      1.30, 4.20). We have shown that IHC identifies women with ER 'poor' tumours for
      whom endocrine manipulation is not appropriate.

PMID- 14965707
TI  - Audit of patient's waiting time to see their family doctor prior to referral to a
      fast-access breast clinic in the era of a guaranteed 2-week wait.
AB  - PURPOSE: A prospective study aimed at assessing the effect of introduction of a
      fast-tract referral system for patients with suspected breast cancer and the
      quality of GP referrals in Barnsley. METHODS: Between February and April 2001, 70
      consecutive patients with symptomatic breast disorders were seen in the fast
      access breast clinic. Mean age=46 years (range 18-84). Ten non-urgent referrals
      seen in the study period were included in the analysis to determine the
      appropriateness of such referrals. Three screening criteria were used to select
      high-risk patients and data were recorded prospectively. Patients were classified
      as urgent, soon or routine based on symptomatology. RESULTS: Of the 70 patients
      seen, 20 were considered as urgent, 20 as soon and 30 as routine. Forty patients
      were seen within the '2-week wait' period. Twelve were classified on clinical
      grounds as malignant. Mean waiting time to see the GP was 2.2 days. Mean waiting
      time to see the specialist breast surgeon was 6.6 days. CONCLUSION: A fast-track
      system for suspected breast cancer has led to a significant reduction in the time
      to diagnosis and initiation of a definitive treatment, with most made within 2
      weeks. Fast-track referrals is not appropriate in all cases.

PMID- 14965708
TI  - Do women newly diagnosed with breast cancer and consulting surgeon assess
      decision-making equally?
AB  - This study assesses the perception of the decision-making process of 25 surgeons
      and 194 patients (aged 21-81 years) who had newly diagnosed breast cancer and had
      to undergo mastectomy or breast-conserving surgery (BCS). The majority of women
      wanted to participate in decision-making. When it was medically possible to give
      a choice between BCS and mastectomy, only 59% of women received a choice. The
      main reason that 11% of the women went against surgeon's recommendations was fear
      of cancer recurrence. The most influential factors for women were the surgeon's
      recommendation, and fear of cancer recurrence. Medical assessment and the
      cosmetic result were the most influential factors for the surgeons. Female
      surgeons were more influenced by their assessment of the women's need for
      security, than male. In conclusion, not all women who are eligible for BCS
      receive an option. Women and surgeons emphasize influencing factors differently.
      The surgeon's gender was found to influence recommendation given.

PMID- 14965709
TI  - Natural history of node-negative breast cancer: are conventional prognostic
      factors predictors of time to relapse?
AB  - The purpose of this study was to determine a subpopulation of node-negative
      breast cancer patients at high risk of metastases and to analyse the relationship
      between conventional prognostic factors and the onset of metastatic disease.
      Patients with node-negative breast cancer, who were not receiving systemic
      adjuvant therapy, were prospectively enrolled into a multicentre study. We
      studied the onset of metastatic disease in relation to family history, age, and
      tumour characteristics of 2683 registered patients, 2213 were available for
      analysis. Median follow-up was 100 months. Metastatic disease-free survival was
      88% at 5 years and 80% at 10 years. The two strongest prognostic factors in a
      multivariate analysis tumour Scraff, Bloom and Richardson (SBR) grade (P<0.0001)
      and size (P<0.02), were used to classify patients into three groups with
      different risks of relapse at 10 years: (1) lowest (8.4%) risk: SBR I and < or =1
      cm; (2) intermediate (20%) risk: SBR I and >1 cm or SBR II or SBR III and < or =2
      cm; (3) highest (32%) risk: SBR II or SBR III and >2 cm. A peak in the incidence
      of metastases was noted between 2 and 4 years, and a nadir between 6 and 8 years,
      after surgery. SBR grade is a highly predictive factor in node-negative breast
      cancer. The time course of the appearance of metastases is not linear. Prognostic
      factors are related to the height of an early peak in the occurrence of
      metastases rather than to the timing of this peak.

PMID- 14965710
TI  - Oncogenes, granules and breast cancer: what has c-myc to do with apocrine
      changes?
AB  - This issue of The Breast includes an elegant study by Selim et al. on c-myc gene
      amplification and protein overexpression in apocrine metaplasia (APM) and
      apocrine adenosis (AA) of the breast using paraffin-embedded tissue. In their
      report, the authors observe that all cases of APM and AA harbored c-myc protein
      overexpression, but no definitive gene amplification was found. Most importantly,
      they observed that the percentage of cells expressing c-myc in APM and AA was
      significantly correlated with cell proliferation, as assessed by Ki-67
      immunolabeling index. On the basis of their findings and of previously reported
      studies, the authors suggest that c-myc overexpression occurs in early stages of
      breast carcinogenesis, that c-myc gene amplification may be a late event, and
      that in APM and AA c-myc overexpression is related to cell proliferation. Selim
      et al. findings have brought to our attention two thorny but rather important
      issues regarding current concepts of apocrine changes and their association with
      breast carcinomas, and also the role of c-myc in breast carcinogenesis.

PMID- 14965711
TI  - C-myc oncoprotein expression and gene amplification in apocrine metaplasia and
      apocrine change within sclerosing adenosis of the breast.
AB  - Overexpression and/or amplification of c-myc oncogene are known to occur in human
      breast carcinomas, particularly those of high grade. Apocrine metaplasia (APM) is
      a common finding within fibrocystic change, and in some cases appears to be
      associated with an elevated risk of subsequent breast cancer. It has been
      suggested that apocrine metaplasia within sclerosing adenosis of the breast, also
      called apocrine adenosis (AA), has a premalignant potential. Little, however, is
      known about cellular level genetic alterations in either APM or AA of the breast.
      Because of this, c-myc expression and amplification in APM and AA were studied.
      Fluorescence in situ hybridisation (FISH) is a methodological approach to
      detecting these genetic alterations. In this study, APM and AA were studied
      immunohistochemically to detect c-myc oncoprotein expression, and FISH was
      employed using a DNA probe for the c-myc gene in archival tissue sections of
      cases of APM and AA of the breast. Nuclear immunostaining for c-myc was seen in
      all APM and AA cases studied, but amplification of the c-myc gene was not seen in
      any cases with APM or AA. The results of this study indicate that c-myc
      overexpression appears to occur early in breast oncogenesis. Amplification of the
      c-myc gene does not occur in APM or AA of the breast, however, suggesting that
      this particular genetic alteration constitutes a late event in the pathogenesis
      of breast carcinomas.

PMID- 14965712
TI  - Microsatellite instability is not a common feature in medullary breast cancer.
AB  - Microsatellite instability (MSI) is a form of genomic instability associated with
      defective DNA mismatch repair in tumors. MSI is found in 85-90% of hereditary
      nonpolyposis colorectal cancer cases; however, its occurrence in breast
      carcinogenesis still remains to be clarified. In addition, data are limited on
      the incidence of MSI in the medullary subtype. The purpose of this study was to
      investigate the occurrence of MSI in medullary breast cancer (MBC). The study
      included a total of 16 patients with MBC, nine with typical and seven with
      atypical histology. The incidence of MSI in five microsatellite loci (D2S123,
      D3S1611, D17S807, D17S796 and Xq11-12) was determined by comparing paired normal
      and tumor tissue DNA after PCR amplification from paraffin-embedded tissues. All
      16 tumors showed stability at five loci. Although the number of microsatellite
      markers and DNA samples may limit the value of our results, we conclude that the
      MSI phenotype is uncommon in human MBC.

PMID- 14965713
TI  - Early detection of malignant process in benign lesions of breast tumor by
      measurements of changes in structuredness of cytoplasmic matrix in circulating
      lymphocytes (SCM test) reinduced in vitro by specific tumor antigen.
AB  - Early detection is crucial for successful treatment of all types of cancer. The
      specificity and sensitivity of the current methods vary from 50% to 80%. The use
      of specific tumor antigens and cytometric technology has resulted in the
      development of a new procedure for the early detection of breast tumors. This new
      method is reported. The test utilizes static cytometry, which records
      polarization and intensity changes in fluorescent light emitted from each
      individual lymphocyte obtained from tumor-bearing patients stimulated by the
      relevant specific tumor antigen. Using MUC-1/SEC as the specific antigen, we
      detected breast tumors with 85% specificity and 81% sensitivity in 137 breast
      tumor-bearing women. A significant linear correlation was found between the SCM
      test and the conventional classification of relative risk for breast cancer in
      benign lesions, suggesting that this is a precise method that could be used in
      mass screening for early detection of breast cancer.

PMID- 14965714
TI  - Isolated erythema (cellulitis) of the breast.
AB  - This paper reports nine cases of breast cellulitis in women patients (four cases
      in pregnancy, four postmenopausal cases following hormone replacement therapy and
      one case of unilateral breast oedema following a mediastinal lymphoma). Biopsies
      were obtained from the erythematous area in one pregnant patient, one
      postmenopausal patient and the patient with breast oedema associated with the
      mediastinal lymphoma. Histology revealed unspecific dermatitis with extensive
      perivascular lymphoplasmocellular infiltrates. Histopathological examination of
      biopsies obtained from the underlying mammary tissue along with the corresponding
      mammographic data gave no evidence of mastitis or mammary carcinoma. The patients
      complained of sensitivity to touch, a feeling of local tightness or a burning
      sensation. These findings were reported in both breasts in the pregnant patients,
      but were unilateral in the others. The submammary fold was unremarkable, that is,
      no intertrigo was detected. The aetiology of the erthyema is probably associated
      with swelling of the breast tissue and a causal link with a specific endocrine
      constellation (pregnancy, postmenopausal HRT) can be postulated. A common factor
      in all cases presented here is the relatively long period of 4 to 13 weeks before
      healing of the lesion. Therapeutic intervention with antibiotics or dopamine
      agonists failed to influence the course. Similarly, steroid cream appeared to be
      of no value in these cases. Extensive erythema of the breast skin is a benign
      disease, for which there is still no known effective therapy. The lack of
      mammographic evidence and, especially, of positive palpatory findings make breast
      cancer highly improbable as the underlying cause.

PMID- 14965715
TI  - Clinical validity of new ultrasound methods in the differential diagnosis of
      breast diseases.
AB  - The clinical application of the extended-field-of-view (EFOV) technique, 3D
      ultrasonography (3D US) and a newly developed US method using a homogeneous
      tissue equivalent phantom, the so-called attenuation in phantom (AIPH) method,
      was evaluated in 200 patients with breast disease. These methods improved
      differentiation both in the preoperative diagnostic and in the postoperative
      follow-up. EFOV made possible to see large or multiple lesions and also their
      vasculature in a single image, allowing exact measurement, comparison and better
      assessment of traditional criteria. In addition, costs and examination time were
      also reduced. The possibility of viewing the spatial arrangement and the internal
      and external surfaces of the lesions improved preoperative decision making.
      Finally, the newly developed AIPH method allowed excellent evaluation of the
      posterior acoustic pattern of the lesions even when the mass was near the chest
      wall. For this reason, it was easier to distinguish malignant lesions from benign
      lesions of the breast.

PMID- 14965716
TI  - Freehand core biopsy in breast cancer: an accurate predictor of tumour grade
      following neoadjuvant chemotherapy?
AB  - Core biopsy is an increasingly used technique in the pre-operative diagnosis of
      breast carcinoma, as it provides useful prognostic information with respect to
      tumour type and grade. Neoadjuvant chemotherapy is being used in the treatment of
      large and locally advanced breast cancers but little is known regarding the
      correlation between tumour histology on pre-treatment core biopsy and that in
      residual tumour following primary chemotherapy and surgery. This study aimed to
      evaluate the accuracy of core biopsy in predicting these features in patients
      treated with primary chemotherapy. One hundred and thirty-three patients with
      carcinoma of the breast diagnosed on clinical, radiological and cytological
      examination underwent core biopsy, followed by primary chemotherapy (with
      cyclophosphamide, vincristine, doxorubicin and prednisolone) and surgery. The
      false-negative rate for pre-treatment core biopsy was 14%, with 91% agreement
      between the grade demonstrated on core biopsy and that in the residual tumour
      following completion of chemotherapy. Tumour type in the residual post
      chemotherapy tumour was predicted by core biopsy in 84%. This study suggests that
      pre-treatment core biopsy histology accurately predicts residual tumour histology
      following primary chemotherapy and surgery in patients with breast cancer.

PMID- 14965717
TI  - Percutaneous stereotactic en bloc excision of nonpalpable breast carcinoma: a
      step in the direction of supraconservative surgery.
AB  - Recently, the advanced breast biopsy instrumentation (ABBI) system has been
      introduced as an alternative to conventional breast biopsy techniques. This study
      was prospectively conducted to evaluate the potential of the ABBI method in
      locoregional management of a consecutive series of patients with nonpalpable
      mammographically detected breast carcinomas. Sixty-one consecutive patients
      underwent an ABBI procedure as a first step before possible surgery for
      nonpalpable breast lesions that would in any case require complete excision. For
      the 27 patients in whom the ABBI biopsy revealed malignancy further surgery was
      recommended, including re-excision of the biopsy site and axillary dissection in
      cases of infiltrating carcinoma. We calculated the probabilities that the ABBI
      specimen would have tumor-free margins and that a definitely complete excision
      had been achieved as a function of the mammographic or pathological diameter of
      the cancer. For cancer with a pathological diameter less than 10 mm measured on
      the ABBI specimen, the probability (92%) of obtaining complete resection was
      significantly better than for larger lesions (P=0.01, Fisher's exact test).
      Although the therapeutic perspectives for the ABBI method are limited at present,
      we suggest that this approach is a first step in the direction of a surgical
      strategy that is better adapted to the pathological characteristics peculiar to
      these small tumors, whose incidence is increasing.

PMID- 14965718
TI  - Is breast cancer care in accord with clinical practice guidelines: a consumer
      audit.
AB  - OBJECTIVES: To assess whether information, support and other psychosocial care
      for women with early breast cancer in Australia is in accord with published
      Australian clinical practice guidelines. DESIGN: An interview survey of a
      population-based sample of women with early breast cancer. SETTING: The whole of
      Australia. PARTICIPANTS: Women diagnosed with early breast cancer 6-12 months
      before the survey were identified through the population-based cancer registries.
      An initial sample of 1184 women was drawn from the cancer registries; the doctors
      of 104 women did not agree to any participation and a further 212 women were
      excluded as ineligible. A randomly selected sample of 832 of the 868 women who
      were eligible to participate were invited to participate in the study and 544
      (76%) of the 716 who could be contacted completed a full interview. MAIN OUTCOME
      MEASURES: A telephone interview covering 12 aspects of care recommended in the
      published guidelines. RESULTS: Most women received care in accord with the
      following recommendations: diagnosis given by a senior doctor (95%), face to face
      (86%) and in an open manner (90%). Fewer women received recommended care in
      relation to: involvement in decision making (73%), information about clinical
      trials (13%); receiving breast reconstruction following mastectomy (8%), evidence
      based consumer guides (62%) and adequate support for families (65%). CONCLUSIONS:
      The extent to which the provision of information, support and psychosocial care
      is in accord with recommendations can be audited effectively by a survey of women
      who have received treatment. Some 80% or more of women received care in accord
      with half of the 12 target guidelines; however, further programmes are required
      to improve access to information and participation in clinical trials and to
      better understand participation in decision making.

PMID- 14965719
TI  - Breast cancer patients have unmet needs for dietary advice.
AB  - GOAL: This study investigated ideas and attitudes of breast cancer patients in
      two countries with reference to information on diet and their need for dietary
      counselling. PATIENTS AND METHODS: Australian breast cancer (ABC) patients
      (n=215) surveyed for alterations in dietary habits after diagnosis were compared
      with breast cancer patients in Finland (FBC; n=139). A validated questionnaire
      was used. Logistic regression models were used to adjust for differences in
      demographic patient characteristics between the groups. RESULTS: Eight per cent
      of FBC and 54% of ABC patients saw diet as a factor contributing to their disease
      (P<0.00001). Thirty per cent of FBC and 39% of ABC reported changing their diet
      after being informed of the diagnosis (P=0.033). Higher education, younger age
      and longer (>1 year) time to diagnosis were significantly associated with the
      probability of changing diet among the Australian patients. The main reason given
      was the desire for cure. The most common source of information was the mass
      media, and a need for more information on dietary factors relating to disease was
      expressed by 32% of patients in each group. CONCLUSION: Ideas about the
      importance of diet varied significantly among ABS and FBC patients. The lack of
      precise dietary recommendations for the individual situation was commonly
      mentioned, and patients depended on information obtained from outside their
      treatment centre.

PMID- 14965720
TI  - Bilateral nipple necrosis in a breastfeeding woman with Behcet's disease.
AB  - Behcet's disease is a chronic, multisystem disorder. A 23-year-old female patient
      diagnosed with Behcet's disease 3 years earlier was admitted with deep ulcers on
      both areolae caused by detachment of the nipples following breastfeeding since
      spontaneous delivery of her baby. Physical examination revealed a necrotic ulcer
      crater 2 cm in diameter on each breast, with the lactiferous ducts draining into
      these. Incisional biopsy sample from the areola ulcer border on the left breast
      showed leukocytoclastic vasculitis. Breastfeeding was stopped, and local wound
      care and systemic corticosteroid therapy were started. After 4 weeks,
      epithelialization tissue filled the ulcers, leveling the crater base with the
      areola. Bilateral nipple necrosis in a breastfeeding woman is a rare entity. It
      is thought that in the present case minor trauma caused by breastfeeding
      accompanied by neutrophilic infiltration resulting from amplified inflammatory
      response and leukocytoclastic vasculitis attributable to Behcet's disease was
      responsible for the necrosis.

PMID- 14965721
TI  - Metastatic disease in the breast.
AB  - Breast cancer is the commonest malignancy in women. However, metastatic
      involvement of the breast is relatively rare. Metastatic disease of the breast is
      therefore often an unexpected diagnosis in a female patient presenting with a
      breast mass. The commonest cause is spread from a contralateral breast carcinoma.
      Of solid tumors at other sites, the most common cancers to metastasize to the
      breast are, in declining order of frequency, malignant melanoma, lymphoma, lung
      cancer, ovarian carcinoma, soft tissue sarcoma, and gastrointestinal and
      genitourinary tumors. Besides these, metastases from osteosarcoma, thyroid
      neoplasms, and cervical, vaginal and endometrial carcinomas to the breast have
      been sporadically reported in the literature. A clinical presentation with pain,
      tenderness and discharge is distinctly unusual. A solitary lesion is the most
      common clinical presentation. Lesions that metastasize to the breast may produce
      changes that look similar to those of primary breast cancer on mammography, but
      they are more likely to be multiple, are frequently bilateral, and form a nidus
      of tumor cells that are usually round with fairly well-defined margins.
      Microcalcifications are not a distinguishing feature, and although their margins
      may be ill defined, spiculations are not commonly found. Diagnosis is generally
      achieved by means of fine-needle aspiration cytology or open biopsy of the breast
      masses. In recent reports, particular importance has been attached to the
      performance of fine-needle aspiration cytology diagnosis, to differentiate a
      metastasis from a second primary tumor, thus making it possible to avoid
      unnecessary mastectomy and ensure that appropriate chemotherapy and radiotherapy
      are implemented.

PMID- 14965722
TI  - Rapid peroperative assessment of axillary lymph node status using imprint
      cytology.
AB  - Sentinel lymph node biopsy for invasive breast cancer is a new technique that has
      been shown to be accurate in staging the axilla. Patients with a positive
      sentinel node will potentially need a second operation to clear the axilla. A
      reliable technique for assessing lymph nodes intraoperatively could potentially
      avoid this second procedure. This study aimed to assess the accuracy of
      peroperative imprint cytology of axillary lymph nodes in patients with invasive
      breast carcinoma. A total of 157 nodes were studied. One-hundred and nineteen
      nodes were both negative on imprint cytology and paraffin section. Thirty-eight
      nodes were positive on imprint cytology. Of these, 37 were positive on histology.
      Imprint cytology is a rapid technique that is inexpensive and has been shown to
      be reliable in this and other studies. It may prove to be of value in patients
      undergoing sentinel lymph-node biopsy for breast carcinoma.

PMID- 14965723
TI  - Genetic variants of calcitonin receptor and breast cancer in Japanese.
AB  - Calcitonin (CT) inhibits the growth of human breast cancer cell lines and
      calcitonin receptor (CTR) is expressed in breast cancer lines and breast cancer
      tissue. In this study, the allele frequencies of the CTR gene were compared in
      the peripheral blood and tumour from 46 breast cancer patients with 50 peripheral
      blood samples from Japanese women. The allele frequencies of CTR gene did not
      differ between them. There was no significant association of CTR allele
      frequencies in invasive breast carcinomas. These results indicate that allelic
      variation of the CTR gene is not a significant risk factor for the development of
      breast carcinoma in Japanese women. Further studies are needed to clarify the
      role of CT and CTR in human breast tissue.

PMID- 14965724
TI  - Contralateral internal mammary node invasion in breast cancer:
      lymphoscintigraphic data.
AB  - Contralateral internal mammary (IM) node invasion has been analyzed in 1025
      patients where the two IM chains have been investigated by lymphoscintigraphy.
      Contralateral IM lymphoscintigrams (LySc) were classified as abnormal (nodes
      involved by metastatic cancer) in 153 cases (or 15.6% of the population) and this
      included one-third of the cases with homolateral IMLySc abnormalities (114/318).
      Overall, patients with bilateral abnormalities on IMLySc (Grp A) had a similar
      survival to those with homolateral abnormal IMLySc (Grp B). However, when other
      prognostic variables were taken into account and two matched groups were
      obtained, patients with bilateral internal mammary node involvement had a highest
      incidence of clinically evident systemic metastatic disease than patients with
      homolateral IM involvement. Contralateral IM nodes are invaded in one-third of
      the cases with homolateral IM node invasion. These patients may have a prognosis
      worse than those with only homolateral IM disease.

PMID- 14965725
TI  - Locally advanced breast cancer: the outcome of primary polychemotherapy based on
      infusional 5 fluorouracil.
AB  - Over a 5-year period, 75 patients with locally advanced breast cancer presenting
      to the Edinburgh Breast Unit were managed with a policy of infusional primary
      chemotherapy. For 65 patients, the regimens comprised infusional 5 fluorouracil
      with anthracycline and/or either cyclophosphamide or cisplatinum (AcF, CAF or
      ECF) whilst 10 older patients had CMF-inf. The overall activity and tolerability
      for the regimens was good with a 76% objective response rate including 15%
      clinical complete responses. Surgery was possible in 64% and pathological
      complete responses confirmed in 7 (9.3%). Median disease free survival (DFS) is
      5.23 years. Factors predicting for DFS or Overall Survival (OS) were assessed in
      this small group and ER positive patients did better than ER negative although
      there was surprisingly no negative DFS or OS association with inflammatory
      disease or advancing age. We found a paradoxical interaction with use of post
      chemotherapy tamoxifen which was significantly associated with poorer DFS and OS
      overall and in the ER negative subgroups.

PMID- 14965726
TI  - Women with normal mammography describing symptoms at screening.
AB  - A retrospective study from May 1989 to June 1995 identified 4327 women with
      symptoms and normal mammography, from a total population of 139,852. The women
      with symptoms were divided into two groups: those who had been recalled for
      assessment, because of potentially significant symptoms, and those who had not.
      Out of 448 women recalled for assessment with significant symptoms, 8
      malignancies were detected and 8 benign biopsies were performed. Review of the
      remaining 3879 women with symptoms showed that 4 had developed interval cancers
      in the same breast as the symptoms described at the previous screening
      attendance. No cancer was detected at subsequent screening examinations. This
      review shows that breast cancer is so uncommon in women attending for screening
      with symptoms that a policy of only recalling women with significant symptoms is
      justifiable.

PMID- 14965727
TI  - Screen detected breast cancer in an Asian population: pathological findings of
      the Singapore breast screening project.
AB  - We document the pathological characteristics of 135 cancers detected in 132
      predominantly Chinese women in the Singapore breast screening project. Thirty
      four (25%) screen detected tumours were in situ ductal cancers; 98 (73%)
      invasive, while three (2%) women with malignant fine needle aspirate smears
      refused further treatment. The median size of in situ cancers was 10 mm; the
      majority (56%) demonstrated a comedo pattern. Of the invasive tumours which had a
      median size of 15 mm, three (3%) were microinvasive, 75 (77%) infiltrative
      ductal, three (3%) invasive lobular, and the remaining 17 (17%) special types or
      others. Histologic grading revealed 23 (24%) grade I, 52 (53%) grade II, 19 (19%)
      grade III and four (4%) ungraded cases. Sixty-three (65%) of the invasive cancers
      were node negative, while 64% of all screen detected malignancies were Stages 0
      (in situ) or I. From the pathological perspective, problems of borderline
      lesions, microinvasion, grade assessment and histological subtyping have to be
      addressed.

PMID- 14965728
TI  - The use of X-ray for lymph node determination in the axillary dissection
      specimen.
AB  - A new and simple method by X-ray is described for lymph node determination in the
      axillary specimen of breast cancer patients. X-rays were performed of the
      axillary specimens of 49 women with breast cancer. The number of lymph nodes
      visible on the X-rays were assessed by two radiologists (A and B). The number of
      nodes identified in the axillary specimens was reported by the pathologist
      independently. The method described shows a clear correlation between the mean
      numbers of nodes counted on the X-rays of the specimens (radiologist A 18.3, B
      16.1 nodes) and the mean numbers of nodes recovered by the pathologist (18.4). No
      intra-observer variation was observed and only a small inter-observer variation
      (2.2 nodes). This method of X-ray determination of lymph nodes can be used in
      auditing the surgeon's accuracy in performing complete axillary dissection as
      well as in auditing the number of lymph nodes found by the pathologist.

PMID- 14965729
TI  - Does open-access mammography and ultrasound delay the diagnosis of breast cancer?
AB  - There is a consensus that open-access breast imaging for general practitioners is
      inappropriate since the process omits an expert clinical examination and fine
      needle aspiration cytology. However, it was decided to test this hypothesis by
      comparing the outcome of breast referrals in a district with both an open-access
      imaging and a one-stop clinic. The time from referral to definitive diagnosis in
      all women with breast cancer was compared over a 12 month period in 1996. Of 1049
      women referred for open-access imaging 20 (2%) were found to have breast cancer
      compared with 91 (9%) of 995 women referred to the one-stop breast clinic. There
      was a longer interval before the diagnosis of breast cancer was made in cases
      referred for open-access imaging compared with cases referred to the one-stop
      breast clinic (mean 63 vs 35 days). However, if patients with advanced disease
      are excluded the mean interval was 63 vs 44 days. The mean tumour size of breast
      cancers in cases referred to open-access imaging was smaller (1.5 vs 2.3 cm),
      there were fewer grade 3 tumours (10% vs 39%), and there was a lower rate of
      axillary lymph node metastases (20% vs 32%) compared with cases referred to the
      one-stop breast clinic. The longer interval for the open-access patients was
      largely due to administrative delay and the 3 patients with a delay of more than
      3 months had all had a triple assessment which was false negative. This study
      does not support the hypothesis that open-access mammography is unsafe and should
      be withdrawn.

PMID- 14965730
TI  - A comparison of invasive breast cancer detected in a screened population with
      invasive breast cancers detected at rapid access diagnostic facilities.
AB  - The objective of this study was to assess the impact of rapid access breast
      diagnostic facilities on the benefit of mammographic breast screening. Invasive
      cancers were compared for maximum diameter in two groups: group A--70 patients,
      with screen detected breast cancer aged 50-65, mean age 55.8; group B--46
      patients, with symptomatic breast cancer aged 50-65, mean age 56.7. Group A
      patients had all been invited for screening and included interval cancers and
      cancers in lapsed attenders. Group B patients were detected at rapid access
      diagnostic facilities. In group A (screened) the invasive cancers had a mean
      diameter of 17.8 mm, with a median of 15 mm. Group B (unscreened) consisted of
      invasive cancers with a mean diameter of 25.2 mm, and a median of 25 mm. Thirty
      two (46%) of the screened cancers were found to be less than 15 mm compared to 5
      (11%) of the unscreened cancers, using the Wilcoxon Rank Sum Test, P<0.001.
      Although rapid access modern diagnostic facilities for breast cancers offer the
      ability to detect early cancers (11% in this survey), screen detected invasive
      cancers remain significantly smaller even when interval cancers and cancers in
      lapsed attenders are included.

PMID- 14965731
TI  - Inflammatory myofibroblastic tumour of the breast: report of a case with giant
      vacuolated cells.
AB  - Inflammatory myofibroblastic tumours (IMTs) or inflammatory pseudo-tumours are
      uncommon lesions of unknown aetiology. The majority of the cases are reported in
      the lungs of young patients. Extra-pulmonary anatomic locations include the
      abdomen and pelvis, but rare cases have been described in the breast. We describe
      an IMT in an 86-year-old female, presenting as a well-circumscribed palpable mass
      in the left breast. Histologically the remarkable feature was the presence of
      giant vacuolated cells intermixed with spindle cells and a prominent plasma cell
      infiltrate immersed in a fibrous hyalinized stroma. Immunohistochemical and
      electron microscopy studies demonstrated the myofibroblastic nature of the giant
      vacuolated cells and the spindle cells, and the polyclonal nature of the plasma
      cells. The morphologic and immunohistochemical findings supported the diagnosis
      of IMT. The biological behaviour of IMT in this age group is unknown and surgical
      excision with close mammographic follow-up is considered to be appropriate
      treatment for this lesion in the breast.

PMID- 14965732
TI  - Small bowel obstruction caused by a solitary metastasis from carcinoma of the
      breast.
AB  - Solitary gastrointestinal metastases from breast cancers are rare and are
      diagnosed late. This paper describes a small bowel breast metastasis discovered
      at laparotomy for small bowel obstruction. A higher index of clinical suspicion
      in these cases may lead to earlier detection and improved patient outcome.

PMID- 14965733
TI  - Hot-water bottle induced thermal injury of the skin overlying Becker's mammary
      prosthesis.
AB  - We report a case of a full thickness burn to the breast following the application
      of a hot-water bottle to the insensate skin overlying a mammary prosthesis.

PMID- 14965734
TI  - Clinical significance of intramammary lymph nodes.
AB  - Intramammary lymph nodes (IMLN) are present in up to 47% of breasts and may be
      involved in metastatic disease in up to 9.8 % of operable breast cancer cases.
      IMLN are likely to be increasingly recognized with wider acceptance of high
      quality screening mammography and the use of ultrasound assessment of breast
      disease. The aim of this study is to demonstrate how IMLN can have an impact on
      management of breast cancer patients by presenting a case series of three
      patients. We conclude that IMLN metastases from breast cancer alters the
      prognosis and hence the management of patients. This will need to be addressed
      more frequently as sentinel node biopsy is more widely utilized.

PMID- 14965735
TI  - Invasive ductal carcinoma of the breast metastatic to the endometrium.
AB  - Two patients with breast cancer which metastasized to the endometrium are
      described.

PMID- 14965736
TI  - Bacterial endocarditis associated with a skin-tunnelled catheter.
AB  - Skin-tunnelled catheters have become an accepted method for establishing long
      term central venous access in patients undergoing treatment for malignancies.
      They allow administration of continuous infusions of cytotoxic drugs,
      supplementation of fluids and blood products, total parenteral nutrition and
      access for the checking of blood tests. It is recognized that there are certain
      complications associated with their use including the risk of infection both of
      the exit site and tunnel, as a source of septicaemia, line-associated thrombosis
      (despite the use of prophylactic low dose warfarin and flushing of the line with
      heparin) and accidental dislodgement of the line. We report a case of bacterial
      endocarditis affecting the pulmonary valve shortly after removal of a skin
      tunnelled catheter due to line-associated brachiocephalic venous thrombosis.

PMID- 14965737
TI  - Langer's axillary arch in association with sentinel lymph node.
AB  - Langer's axillary arch is a relatively rare anatomical variation of latissimus
      dorsi muscle insertion. The clinical importance of this condition in axillary
      lymph node dissection (ALND) and lymphoedema as well as latissimus dorsi flap
      reconstruction has been described previously. Axillary vein obstruction in
      association with this condition has also been reported. We report two cases of
      Langer's axillary arch encountered during sentinel lymph node (SLN) biopsy which
      had some bearing on the procedure.

PMID- 14965738
TI  - Review of internal mammary chain irradiation in breast cancer.
AB  - The aim was to assess the effectiveness of and indications for irradiation of the
      internal mammary chain (IMC) in the treatment of breast cancer based on a review
      of the literature. A computerized literature search was performed of the MEDLINE
      database from 1966 to March 1998. The data retrieved were ranked into levels of
      evidence as per convention. There was no Level I evidence found. Six randomized
      controlled trials and nine retrospective series were found pertaining to early
      stage breast cancer. Although some retrospective data suggested that IMC
      irradiation improved survival in mediocentral and axillary node-positive tumours,
      this was not supported by the randomized data. Two randomized trials were
      identified in high risk operable breast cancer. One of these showed a survival
      advantage to post-mastectomy irradiation, but the contribution of IMC irradiation
      to this could not be delineated. Based on the best current evidence, there is no
      advantage to elective IMC irradiation. The only indication is for positive IMC
      nodes where the management aim is palliative. The ongoing EORTC randomized trial
      may provide the definitive answer.

PMID- 14965739
TI  - Quantification of microvessel density of breast carcinoma: an assessment of the
      inter- and intraobserver variation.
AB  - The density profile of microvessels (MVD) has recently emerged as a
      prognostically independent morphological marker of various malignancies,
      including carcinoma of the breast. MVD-scoring may thus afford the pathologist
      the opportunity to identify subsets of early stage breast cancer patients, which
      may benefit from adjuvant therapy. Reproducibility studies are, however,
      mandatory. Fifty sections of invasive breast carcinoma, immunolabelled for Factor
      VIII-related antigen, were scored independently by two observers for the number
      of vessel-profiles (v-p) in the following manner: 1) 250 randomly selected high
      power fields (HPF) were scored by two analysts to evaluate the agreement of the
      counting per se; and 2) the hot spot(s), i.e. the zones considered the most
      vessel rich, in the 50 sections were identified and scored twice to evaluate the
      agreement on selecting hot spots. When the observers evaluated MVD in the very
      same 250 HPF a median deviation of 2 v-p (10%) was produced. The interobserver
      disparity was further accentuated when the participants independently had to
      identify the hot spots with a median deviation of 6 v-p (13%). Intraobserver
      variation was approximately equal to the interobserver discordance. Divergences
      were most conspicuous in fields with a complex vasculature. In conclusion the v-p
      scoring resulted in substantial inter- and intraobserver variation both in
      selecting hot spots and in performing the scoring per se. Alternative-scoring
      techniques, including strict stereological principles, should be considered in
      the morphological evaluation of angiogenesis.

PMID- 14965740
TI  - Image-guided breast biopsy: analysis of pain and discomfort related to technique.
AB  - A prospective study to evaluate the pain experienced during image-guided core
      biopsy and fine-needle aspiration (FNA) in a series of 200 woman. There was no
      significant difference between the pain experienced between core biopsy and FNA.
      Pain experienced was operator dependent with one of the three radiologists
      causing significantly more pain than the other two.

PMID- 14965741
TI  - Fine needle aspiration cytology in the UK breast screening programme: a national
      audit of results.
AB  - The National Breast Screening Service in the UK depends upon triple assessment,
      with or without core biopsy, to determine the need for diagnostic biopsy or
      treatment for screen-detected lesions. To determine the efficacy of cytology in
      this process a nationwide survey of sensitivity and specificity of the technique
      was instituted by the National Coordinating Committees for both Radiology and
      Pathology. Although some units were performing to the national recommended
      standards, a significant number of units were shown to have problems with a high
      false negative rate and high inadequate rates from lesions which were eventually
      diagnosed as cancer. This suggests problems in localizing lesions adequately at
      aspiration. Generally, indicators of pathology diagnostic performance (e.g.
      positive predictive values) were good. The figures suggest that some units are
      not benefiting from an optimal cytological service. Consequently training
      programmes targeted at aspiration technique may be beneficial.

PMID- 14965742
TI  - Value of routine 99mTc-MDP bone scintigraphy in the detection of occult skeletal
      metastases in women with primary breast cancer.
AB  - Baseline staging bone scans in 208 women with primary breast cancer in University
      Hospital Kuala Lumpur from January 1993 to December 1995 were reviewed. A
      positive bone scan was found in 14.7% of women aged below 50 years, and 9.1% of
      women aged 50 years and above. No patient with T0/T1, 4.7% with T2, 6.6% with T3
      and 35.8% with T4 tumours had a positive scan caused by bone metastases. No
      patient with clinical Stage 0/1, 4% with Stage 2, 9.5% with Stage 3 and 63% with
      Stage 4 disease had a positive bone scan. Clinical staging alone was inaccurate
      in 20.2% of patients. Forty per cent of patients with a positive bone scan did
      not have bone pain. The false positive rate was 0.5% and the false negative rate
      was 0.96%. We conclude that a routine bone scan is not required in Stage 1
      disease or T1 tumours, is indicated in Stage 3 and 4 disease, or T3 and T4
      tumours, and should only be performed in selected women with Stage 2 or T2
      cancers.

PMID- 14965743
TI  - Evaluation with breast scintigraphy of breast lesions of indeterminate
      significance after conventional triple diagnostic approach.
AB  - The role of breast scintigraphy in the evaluation of 30 women with an uncertain
      diagnosis following triple assessment was investigated. Scintigraphy was positive
      in 7 of 13 cancers and 3 of 17 benign lesions and dubious in 1 of 13 cancers and
      2 of 17 benign lesions. Sensitivity ranged from 61.5% to 53.8% depending whether
      dubious lesions were designated as positive or negative. This study shows that
      breast scintigraphy is not sufficiently sensitive or specific to use in the
      evaluation of lesions of uncertain diagnosis following triple assessment.

PMID- 14965744
TI  - Symptoms 2 weeks, 3 months and 12 months after treatment of early breast cancer:
      the patients' perspectives.
AB  - The physical symptoms and side-effects reported by patients treated for early
      breast cancer with surgery (S), (breast conservation or mastectomy), radiotherapy
      (R) and chemotherapy (C) are reported. As part of a large quality-of-life study,
      eligible patients were invited to complete a questionnaire at three and 12 months
      after treatment for early breast cancer. Symptoms 2 weeks after surgery were
      retrospectively collected at the 3-month questionnaire. Comparing the commonly
      used different therapy combinations (S, S+R, S+C and S+R+C) we found the only
      loco-regional symptom to show a significant difference between these groups was
      chest tightness (P<0.001). Both anxiety about attending for and discomfort during
      C were significantly higher than during R (P<0.00005 and 0.00001 respectively).
      We found that the addition of R and, or, C to S resulted in surprisingly little
      variation in physical side-effects.

PMID- 14965745
TI  - Phyllodes tumour of the breast: a retrospective analysis of 30 cases.
AB  - Phyllodes tumour (PT) is a rare neoplasm of the female breast that resembles
      fibroadenoma but occurs in an older age group. We retrospectively reviewed the
      medical records of 30 women who were treated for phyllodes tumour in our centre.
      Histological examination was performed by an experienced breast pathologist in
      all cases and tumours were classified as benign, border line malignant or
      malignant according to standard histological criteria. The mean age at diagnosis
      was 49 years (range: 19-80 years). Twenty-one (70%) of 30 tumours were benign and
      9 (30%) were malignant (n=7) or borderline malignant (n=2). The mean tumour size
      was 46 mm (range: 20-100 mm). The final microscopic margins contained tumour in
      13 (43%) of 30 cases and were free of tumour in 17 (57%) of 30 patients. After a
      median follow-up period of 6 years (range: 6 months-20 years), the tumour
      recurred locally in 5 (17%) patients. One patient had six local recurrences over
      an 18-year period. Local recurrences were more frequently observed in patients
      with malignant tumours compared with those with benign lesions (33% versus 10%).
      However, this association failed to reach statistical significance. There was no
      association between local recurrence, patient age, tumour size or positive
      microscopic margins. There was one death (3%) associated with a completely
      excised malignant tumour. The present study suggests that histological type and
      margins do not accurately predict the clinical course of PT and that there is a
      need to identify novel biological markers that more accurately predict the
      behaviour of this rare neoplasm.

PMID- 14965746
TI  - Stewart-Treves syndrome after treatment for breast cancer.
AB  - This study reviews 3 cases of angiosarcoma of the upper extremity after
      mastectomy and radiotherapy for breast cancer (Stewart-Treves syndrome).
      Angiosarcoma was diagnosed an average 14 years (from 6.5 to 26 years) after
      treatment for breast cancer. Presenting signs included a red raised lesion, a
      palpable mass, a blister appearance (in one case). Two of our three patients
      underwent surgical treatment: one patient underwent local excision followed by
      chemotherapy, and the other patient wide excision, followed by external beam
      radiotherapy. Local recurrence occurred in one of these two patients and was
      followed by the development of lung metastases. The second patient who had
      treatment is free of disease without problems. The third patient refused any
      treatment and died 5 months later. The purpose of this article is to add to the
      literature 3 new cases of Stewart-Treves syndrome and to discuss some specific
      problems of this rare tumour.

PMID- 14965747
TI  - Is there a role for surgery in the treatment of mastalgia?
AB  - Breast pain is a common condition affecting most women at some stage in their
      reproductive life. Mastalgia is resistant to treatment in 6% of cyclical and 26%
      non-cyclical patients. Surgery is not widely used to treat this condition and
      only considered in patients with severe mastalgia resistant to medication. The
      aims of this study were to audit the efficacy of surgery in severe treatment
      resistant mastalgia and to assess patient satisfaction following surgery. This is
      a retrospective review of the medical records of all patients seen in mastalgia
      clinic in the University Hospital of Wales, Cardiff since 1973. A postal
      questionnaire was distributed to all patients who had undergone surgery. Results
      showed that of the 1054 patients seen in mastalgia clinic, 12 (1.2%) had
      undergone surgery. Surgery included 8 subcutaneous mastectomies with implants (3
      bilateral, 5 unilateral), 1 bilateral simple mastectomy and 3 quadrantectomies (1
      having a further simple mastectomy). The median duration of symptoms was 6.5
      years (range 2-16 years). Five patients (50%) were pain free following surgery, 3
      developed capsular contractures and 2 wound infections with dehiscence. Pain
      persisted in both patients undergoing quadrantectomy. We conclude that surgery
      for mastalgia should only be considered in a minority of patients. Patients
      should be informed of possible complications inherent of reconstructive surgery
      and warned that in 50% cases their pain will not be improved.

PMID- 14965748
TI  - Leiomyoma of the breast: case report and review of the literature.
AB  - We describe a case of leiomyoma in the breast in a 48-year-old woman. The main
      clinical-pathologic features together with the differential diagnosis, and the
      pertinent literature reviewed.

PMID- 14965749
TI  - Internal mammary node relapse following breast conservation: a case for
      reirradiation.
AB  - Internal mammary node involvement in early breast cancer is a prognostic factor
      of uncertain significance. This paper addresses isolated regional recurrence at
      this site following breast conservation radiotherapy. A case is presented of a
      woman who developed an internal mammary recurrence after lumpectomy and breast
      irradiation. This recurrence was diagnosed as a bone metastasis, a common mistake
      which may lead to suboptimal management. The true incidence of regional
      recurrences in the internal mammary nodes has been underestimated and their
      clinical significance has not been appreciated. Salvage procedures for local
      control and long-term cure are likely to be successful if the diagnosis is made
      before distant metastases have occurred and a lengthy period has elapsed since
      initial treatment was given. The role of reirradiation should be considered as
      the tissues at this site will generally tolerate a second course of radical
      radiotherapy given more than 10 years after the first.

PMID- 14965750
TI  - Epithelioid haemangioendothelioma of the breast.
AB  - This article describes histopathological, immunohistologic, and morphometric
      features of an epithelioid haemangioendothelioma that presented in the breast of
      a 30-year-old woman. Histologically the tumour was composed of large round,
      polygonal, slightly spindle shaped endothelial cells lying in a myxoid matrix.
      The lesion exhibited primitive vasoformation characterized by the presence of
      cytoplasmic vacuoles. The tumour cells reacted positively to F-VIII related
      antigen, whereas mammary ducts entrapped by the tumour cells reacted positively
      with keratin. Although the breast is an unusual location for this type of lesion,
      epithelioid haemangioendothelioma should be considered a rare differential
      diagnosis of a breast mass.

PMID- 14965751
TI  - Management of the contralateral breast in patients with hereditary breast cancer.
AB  - Approximately 5% of all breast cancers arise on a background of one of the high
      risk breast cancer genes (hereditary breast cancer and hereditary breast and
      ovarian cancer). An estimated 20% of cases arise in the presence of a less
      striking family history with later average age at onset and lower penetrance,
      familial breast cancer. For hereditary breast cancer, bilaterality is a
      recognized feature. Cancers often present at an early age with the contralateral
      risk high. This article explores the current state of knowledge regarding
      management options for women with hereditary breast cancer.

PMID- 14965752
TI  - Serum tumour markers: from quality control to total quality management.
AB  - Since the first clinical use of tumour markers, quality assurance has been
      considered only in a restrictive manner, that is, as a surveillance of the
      analytical process. In other words, quality assessment was roughly viewed as a
      synonymous with quality control. This is not surprising, since tumour markers are
      almost exclusively assayed by radioimmunoassays, whose analytical performance
      were suboptimal in the 1970s. Furthermore, tumour marker concentrations in
      biological fluids were very low (in the ng range); in addition, primary standards
      were not available and dose-response curves were set up with conventional
      calibrators. Therefore, quality control programmes have become mandatory to
      restrict intra- and inter-laboratory variability.

PMID- 14965753
TI  - Junior doctor training in breast and axillary examination: a comparative study.
AB  - To date, there has been a lack of published data concerning the training of
      breast and axillary examination, yet this remains an essential part of the triple
      assessment of breast lumps. In this study, we aimed to determine the competence
      of junior doctors in examining the breast and axilla, and whether this skill
      improved with time. We compared the findings of a specialist registrar and senior
      house officer with those of a consultant in 15 consecutive one-stop breast
      clinics in a district general hospital. The results suggested that although
      specialist registrars become proficient after this period, senior house officers
      do not progress at the same rate. This may have important implications for
      training and the organization of breast clinics.

PMID- 14965754
TI  - Squamous cell carcinoma of the breast.
AB  - Squamous carcinoma of the breast (SCB) is a rare entity. For its diagnosis, the
      exclusion of squamous cell carcinoma of local cutaneous structures and metastasis
      of distant squamous carcinoma are mandatory. The aim was to retrospectively
      evaluate the prevalence, epidemiological and clinical characteristics of the
      cases of SCB, studied in our institution, between January 1985 and December 1996.
      The diagnosis was histopathological. We studied the patients' demographic data
      and tumour characteristics. In the 11-year study period, 5791 patients with
      breast carcinoma were admitted to our Institution, seven (0.1%) of which were
      SCB. All seven patients were female and Caucasian. Their average age was 63 years
      (range 24-82). The presentation was always a breast lump. Five patients were in
      Stage II-A and two in Stage II-B. All tumours were hormone-receptor negative. The
      initial treatment was surgery and four patients received adjuvant radiotherapy.
      The median follow-up was 64 months. No relapses were diagnosed. SCB is a rare
      entity. The initial therapeutic approach should be surgical. There is still no
      consensus regarding adjuvant therapy. The prognosis of this type of breast cancer
      is still the subject of controversy with some series, including the present
      study, suggesting an indolent clinical course and a relatively good prognosis.

PMID- 14965755
TI  - Influence of age and menopausal status on pathologic and biologic features of
      breast cancer.
AB  - The distribution of the main prognostic factors in different age groups was
      evaluated in 1226 patients operated on for primary breast cancer, in order to
      identify those influenced by age and/or menopausal status. Patients were divided
      into the following groups: 1) 40 years of age and under; 2) premenopausal over 40
      years of age; 3) postmenopausal under 75 years of age and 4) 75 years of age and
      over. Our findings showed that the youngest patients had the worst prognostic
      pattern, which improves as age increases and is the best in patients over 75
      years of age. Some of the parameters investigated (tumour size, histologic and
      nuclear grade, tumour infiltrating lymphocytes, p53 and Ki 67) were found to be
      influenced by age, some (necrosis and oestrogen receptors) were influenced by
      menopausal status and/or age, some (vascular invasion, ploidy, S-phase and
      progesterone receptors) showed significant differences in different age groups
      but there was no consistent relation with patient age or menopausal status, and
      others (node status, ErbB2/Neu and Cathepsin D) were not influenced by age or
      menopause.

PMID- 14965756
TI  - Preoperative mammographic features predict clinicopathological risk factors for
      the development of local recurrence in breast cancer.
AB  - This study attempts to correlate preoperative mammographic features with
      established clinicopathological risk factors for local recurrence with a view to
      selecting patients who might be unsuitable for breast-conserving surgery. A total
      of 357 patients underwent surgery for invasive breast cancer. All patients'
      preoperative mammograms were reviewed by a single radiologist (LW) blinded to
      clinicopathological features. The independent sample t-test and chi-squared tests
      were used to correlate preoperative mammographic features with established
      clinicopathological risk factors for the development of local recurrence. The
      presence of extensive in situ disease within the tumour was associated with both
      casting calcification and absence of a mammographic nidus (P=0.0001 and 0.002
      respectively) but not with mammographic density. Furthermore casting
      calcification (P=0.003), absence of a mammographic nidus (P=0.027) and maximum
      nidus size (P=0.014) were all predictors of tumour bed positivity. This study has
      demonstrated that preoperative mammograms can be used to identify those patients
      at risk of occult disease and help select those patients that may be unsuitable
      for breast-conserving surgery.

PMID- 14965757
TI  - Current patterns of referral in breast disease.
AB  - The aim was to audit symptomatic referrals to this breast unit in 1998, in order
      to ascertain the main diagnosis in relation to age, and thereby identify the
      percentage and age of patients who were reassured and discharged without
      investigation. 3199 general practitioner referrals were seen in 1998. Of these,
      8.7% (n=274) were diagnosed as cancer and 91.3% (n=2925) were given a non
      malignant diagnosis. In those under 40 years, only 18 patients of the 1231 seen
      were diagnosed with cancer, and only one of these was younger than 30 years (29
      years). Twenty-seven per cent (n=333) of women under 40 were diagnosed as normal,
      and of these 14% (n=174) had no investigation. We confirm the recommendations of
      the guidelines issued by the Department of Health, that in younger women without
      discrete lumps or family history, clinical examination and reassurance is
      adequate. This audit should therefore empower general practitioners, to
      confidently reassure the younger patient, without a discrete lump.

PMID- 14965758
TI  - Single-agent gemcitabine as second- and third-line treatment in metastatic breast
      cancer.
AB  - In the present study, 25 patients with breast cancer pretreated with one or two
      anthracycline-based regimens for visceral metastases were enrolled. Patients were
      treated with gemcitabine 1250 mg/m2 on days 1, 8 and 15, q28d. Nine patients
      received gemcitabine as second-line treatment, whereas 16 patients received
      gemcitabine as third-line cytotoxic treatment, respectively. In the second-line
      setting, two (22%) patients gained PR (RR 22%) and four (44%) patients
      experienced SD (P=0.2), respectively. In the third-line-setting, one (6%) patient
      gained CR, one patient PR (6%) and four patients (25%) SD, respectively,
      resulting in a response rate (RR) of 12%. In the second-line-setting, median time
      to progression was 5.1 +/- 4.0 months (range: 1.6-13.9) versus 3.5-2.5 months
      (range: 1.3-10.4) in the third-line-setting. Median overall survival was 12.6 +/-
      9.1 months (range: 3.9-30.8) versus 7.5 +/- 6.7 months (range: 2.0-26.0),
      respectively. Overall, no patient experienced treatment limiting toxicities. We
      conclude from the present study that gemcitabine induced an overall RR of 16%
      following prior treatment with anthracyclines. However, median time to
      progression and median overall survival were limited. In the search for
      efficacious treatment of patients with metastatic breast cancer, gemcitabine
      constitutes a valid tool in anthracycline-resistant disease and thus might
      represent a valuable option for combination chemotherapy in controlled trials in
      this condition.

PMID- 14965759
TI  - Male cancer: a qualitative study of male breast cancer.
AB  - Breast cancer is a rare condition in males. There is a dearth of information
      about the psychological and social impact of this condition. Data from six in
      depth interviews with men who had breast cancer identified seven major issues.
      These were associated with delay in diagnosis, shock, stigma, body image, causal
      factors, the provision of information and emotional support. The findings from
      this small study suggest that there are psychological and social factors for men
      diagnosed with breast cancer which have implications for their care and
      management. The recommendations arising from this study are the development of a
      structured education programme aimed at all primary health-care professionals;
      with availability of pre and postoperative gender-specific information to
      alleviate the potential psychological problems associated with the diagnosis; and
      provision of appropriate support/counselling services for partners of patients.

PMID- 14965760
TI  - A breast complication of intravenous drug abuse.
AB  - Breast infection is now much less common than it used to be. It most commonly
      occurs in women in the 18 to 50 age group, and can be divided into lactational
      and non-lactational infection. The most common causative organism is
      Staphylococcus aureus, although enterococci and Anaerobic streptococci are also
      seen in non-lactational infection. An unusual case is reported with a new
      aetiology for breast sepsis.

PMID- 14965761
TI  - Expression and purification of a recombinant avidin with a lowered isoelectric
      point in Pichia pastoris.
AB  - A recombinant glycosylated avidin (recGAvi) with an acidic isoelectric point was
      expressed and secreted by the methylotrophic yeast Pichia pastoris. The coding
      sequence for recGAvi was de novo synthesized based on the codon usage of P.
      pastoris. RecGAvi is secreted at approximately 330mg/L of culture supernatant.
      RecGAvi monomer displays a molecular weight of 16.5kDa, as assessed by ESI mass
      spectrometry. N-terminal amino acid sequencing indicates the presence of three
      additional amino acids (E-A-E), which contribute to further lowering the
      isoelectric point to 5.4. The data presented here demonstrate that the P.
      pastoris system is suitable for the production of recGAvi and that the
      recombinant avidin displays biotin-binding properties similar to those of the hen
      egg white protein.

PMID- 14965762
TI  - Hyperexpression and purification of biologically active human luteinizing hormone
      and human chorionic gonadotropin using the methylotropic yeast, Pichia pastoris.
AB  - The glycoprotein hormones, luteinizing hormone (LH), human chorionic gonadotropin
      (hCG), thyroid stimulating hormone (TSH), and follicle stimulating hormone (FSH),
      play important roles in overall physiology and reproduction. These hormones are
      heterodimeric molecules consisting of an identical alpha subunit non-covalently
      associated with the hormone-specific beta subunit. The inherent structural
      intricacies possessed by these hormones make them very interesting model systems
      for structure-function relationship studies of complex dimeric glycoproteins. The
      structural studies, as well as, the therapeutic applications require large
      quantities of biologically active hormones free of any contaminants. In this
      study, we report hyperexpression and purification of biologically active
      recombinant hLH and hCG expressed using Pichia pastoris expression system. A
      combination of hydrophobic interaction chromatography and ion exchange
      chromatography has been used to purify these recombinant hormones to homogeneity.
      Using a number of biochemical and immunological criteria, the recombinant
      hormones have been shown to be similar to the natural hormones and were equally
      biologically active. The preliminary data also suggested that P. pastoris cells
      express a low molecular weight isoform of hCG that appeared to be less
      glycosylated. This isoform exhibited lesser affinity for the receptor as compared
      to hCG, but was found to be fully biologically active.

PMID- 14965763
TI  - Production of recombinant CART peptides in Escherichia coli with agonist and
      antagonist effects on food intake in rats.
AB  - CART (Cocaine- and Amphetamine-Regulated Transcript) peptides modulate food
      intake and psychostimulant drug actions. Several CART peptides that contain
      multiple disulfide bonds were produced by overexpression in Escherichia coli
      bacteria as fusion products with a C-terminal histidine tag. Since these peptides
      were found denatured in inclusion bodies, in vitro refolding was used to
      reconstitute their biological activity. These CART peptides were tested for their
      ability to inhibit food intake in rats. Of recombinant rat CART peptides 1-102
      long, 1-102 short, and 55-102, only CART peptide 55-102 dose-dependently
      inhibited neuropeptide Y stimulated food intake in rats. This effect was
      dependent on refolding of the peptide since the unfolded version was unable to
      inhibit food intake. Unfolded CART peptide 55-102 HIS tag, but not CART peptide 1
      102 HIS tag, stimulated food intake in rats treated with NPY or vehicle. This
      effect of unfolded CART peptide 55-102 was consistent with that of an antagonist
      and is the first description of one. These studies showed that production of CART
      peptides by bacterial expression is a viable alternative to current methods.

PMID- 14965764
TI  - Soluble expression of a functionally active Plasmodium falciparum falcipain-2
      fused to maltose-binding protein in Escherichia coli.
AB  - Falcipain-2 (fp2) is a hemoglobinase required for supplying peptides and amino
      acids for the proliferation of Plasmodium falciparum in blood. The prospect of
      circumventing its activity thereby serves as a potential strategy for mining
      drugs for anti-malarial therapy. However, to date, efforts to express soluble and
      active fp2 in Escherichia coli have been futile. To overcome this problem, fp2
      was expressed under an array of conditions including the exploitation of multiple
      gene constructs in eukaryotic and prokaryotic hosts. A series of experiments led
      to the finding that the placement of maltose-binding protein (MBP) before the fp2
      mature domain was best in availing the soluble expression of the protease. The
      results also indicate that the prodomain impaired the bacterial expression of the
      protease and the amino acid residues at the N-terminal segment of mature fp2 can
      have a significant effect on the folding and solubility of the enzyme. The
      overexpressed MBP-fp2 fusion protein was purified and shown to be functionally
      active, providing a very useful alternative to the use of resolubilized enzyme
      for future study of structure and function of fp2.

PMID- 14965765
TI  - Overexpression and purification of untagged polynucleotide phosphorylases.
AB  - We report here the development of new, straightforward procedures for the
      purification of bacterial polynucleotide phosphorylases (PNPases). The pnp genes
      from Streptomyces antibioticus, Streptomyces coelicolor, and Escherichia coli
      were overexpressed using the vectors pET11 and pET11A in E. coli BL21(DE3)pLysS.
      The enzymes were purified to apparent homogeneity after phosphorolysis in crude
      extracts followed by anion exchange and hydrophobic interaction chromatography.
      Yields of 5-15mg per liter of culture were obtained and the enzymes contained
      only small amounts of contaminating RNA as estimated from the A(280/260) ratios
      of purified preparations. All three enzymes were active in both the
      polymerization and phosphorolysis reactions normally catalyzed by PNPases.
      Incubation under phosphorolysis conditions but in the absence of potassium
      phosphate indicated that the enzymes were free of phosphate-independent nuclease
      activity. We suggest that the approaches described here may be applied generally
      to the overexpression and purification of eubacterial polynucleotide
      phosphorylases.

PMID- 14965766
TI  - Purification and characterization of a serine protease and chitinases from
      Paecilomyces lilacinus and detection of chitinase activity on 2D gels.
AB  - The filamentous fungus Paecilomyces lilacinus is currently developed as a
      biocontrol agent against plant parasitic nematodes. Nematode eggs and cuticles
      are the infection sites for biocontrol agents that penetrate by the production of
      lytic enzymes. P. lilacinus was cultured in liquid media and proteases and
      chitinases were induced by the introduction of egg yolk and chitin, respectively.
      A serine protease was purified from a culture medium using Sepharose-bacitracin
      affinity column. The protease occurred in three forms, two of which were C
      terminally truncated. Chitinase activity was also observed in the culture
      supernatant, and after separation by isoelectric focusing six proteins were
      detected that showed activity. Chitinase activity was further confirmed on non
      denaturing one-dimensional (1D) and two-dimensional (2D) gels using a sandwich
      assay with glycol chitin as a substrate. Two of the proteins had similarities
      with endochitinases as shown by their N-terminal amino acid sequences.

PMID- 14965767
TI  - DnaK and DnaJ facilitated the folding process and reduced inclusion body
      formation of magnesium transporter CorA overexpressed in Escherichia coli.
AB  - Overexpression of CorA, the major magnesium transporter from bacterial inner
      membrane, in Escherichia coli resulted in the synthesis of 60mg of protein per
      liter of culture, most of which however was in the form of inclusion bodies. The
      levels of inclusion body formation were reduced by lowering the cell culture
      temperature. To dissect CorA inclusion body formation and the folding process
      involved, we co-expressed the protein with various chaperones and other folding
      modulators. Expression of DnaK/DnaJ (Hsp70) prevented inclusion bodies from
      forming and resulted in the integration of more CorA into the membrane.
      GroEL/GroES (Hsp60/Hsp10) were less effective at reducing CorA inclusion body
      formation. Co-expression with either Ffh/4.5S-RNA, the signal recognition
      particle, or SecA, the ATPase that drives protein insertion into the membrane,
      had little effect on CorA folding. These results indicate: (1) that CorA
      inclusion bodies form immediately after synthesis at 37 degrees C, (2) that CorA
      solubility in the cytosol can be increased by co-expressing a chaperone system,
      (3) membrane targeting is probably not a rate-limiting factor, and (4) that
      membrane insertion becomes a limitation only when large amounts of soluble CorA
      are present in the cytosol. These co-expression systems can be used for producing
      other membrane proteins in large quantities.

PMID- 14965768
TI  - Stable isotope labeling of a Group A Streptococcus virulence factor using a
      chemically defined growth medium.
AB  - A secreted, hypervariable virulence factor called the streptococcal inhibitor of
      complement (Sic) has been linked to the reemergence of epidemics due to the human
      pathogenic bacterium Group A Streptococcus. This paper describes a method for
      expressing and purifying Sic from an attenuated GAS strain using a chemically
      defined growth medium. This method was used to label specific amino acid residue
      types in Sic with forms containing the magnetically active isotope (15)N, at the
      amide nitrogen. The (15)N-labeling of Sic permits a detailed investigation of the
      structure and dynamics of the protein using nuclear magnetic resonance
      spectroscopy. The level of stable isotope incorporation was established using
      mass spectrometry and nuclear magnetic resonance spectroscopy.

PMID- 14965769
TI  - Cloning, purification, and characterization of thermostable hypoxanthine-guanine
      phosphoribosyltransferase from Thermoanaerobacter tengcongensis.
AB  - Hypoxanthine-guanine phosphoribosyltransferase (HGPRT, EC 2.4.2.8) from a newly
      characterized thermophile Thermoanaerobacter tengcongensis was expressed in
      Escherichia coli and purified. Analytical gel filtration suggested that the
      enzyme exist as a homotetramer in solution. The optimal pH for the forward
      reaction was found to be 8.0 and the optimal temperature 70 degrees C. The steady
      state kinetic characteristics suggest that hypoxanthine is the most effective
      substrate. This enzyme showed a half-life of 75min at 50 degrees C and no
      apparent loss of activity after 3 months at 4 degrees C.

PMID- 14965770
TI  - Purification of Fab fragments from a monoclonal antibody papain digest by
      Gradiflow electrophoresis.
AB  - Fab fragments isolated from papain digests of monoclonal antibodies have a wide
      variety of uses in analytical and in both in vivo and in vitro diagnostic
      applications. A novel, non-affinity method which uses the Gradiflow to purify Fab
      fragments from the papain digest of a mouse IgG1 anti-c-myc monoclonal antibody
      is described. The Gradiflow is a preparative electrophoresis instrument that uses
      polyacrylamide membranes of known pore size to separate proteins in solution in
      their native state under mild pH conditions by charge or size. The Fab and Fc
      fragments from the papain digestion were characterized using isoelectric focusing
      (IEF) and non-reducing SDS-PAGE in conjunction with IEF and Western blot. There
      were three Fab isoforms with p [Formula: see text] between pH 6.5 and 7.4 while
      the Fc had a range of isoforms between 6.1 and 6.3. Both Fab and Fc fragments had
      similar [Formula: see text] of 50kDa. A charge-based purification strategy was
      developed to obtain a high purity Fab preparation after 10min, confirmed by
      Western blot and chemiluminescence analyses. A small quantity of residual
      undigested IgG1 remained and was removed using a size-based separation. The
      efficiency of the separation despite the narrow pH range between Fab and Fc
      suggests that this technique may be an alternative to protein A or G affinity
      separation of Fc and Fab monoclonal antibody fragments from papain digests of
      monoclonal antibodies.

PMID- 14965771
TI  - A favorable solubility partner for the recombinant expression of streptavidin.
AB  - Recombinant streptavidin is extremely difficult to express at high levels in the
      cytoplasm of Escherichia coli without the formation of inclusion bodies. Fusing a
      solubility enhancing partner to an aggregation prone protein is a widely used
      tool to circumvent inclusion body formation. Here, we use streptavidin as a
      target protein to test the properties of N-terminal fragments of translation
      initiation factor IF2 from E. coli as a solubility partner. Domain I (residue 1
      158) of IF2 is superior to the well-established solubility partners maltose
      binding protein (MBP) and NusA for soluble expression of active streptavidin. The
      number of active streptavidin molecules isolated by chromatography is increased
      threefold when domain I is used as solubility partner as compared to MBP or NusA.
      The relatively small size, high expressivity, and extreme solubility make domain
      I of IF2 an ideal partner for streptavidin and may also prevent other recombinant
      proteins such as ScFv antibodies from being expressed as insoluble aggregates in
      the cytoplasm of E. coli.

PMID- 14965772
TI  - Efficient isolation, purification, and characterization of the Helicoverpa zea
      VHDL receptor.
AB  - The study of fat body receptors (e.g., VHDL receptor) in Lepidoptera has been
      irksome due to the fact that isolation and purification of these proteins are
      difficult and resulted in extremely low yields. A rapid and efficient method is
      presented for the purification of Helicoverpa zea VHDL receptor by the use of
      VHDL-biotin ligand complexed to streptavidin coated magnetic beads. The technique
      can be easily applied to other ligands and allows for the purification of
      membrane proteins with higher yields compared to previously used methods
      involving immunopurification. Although the purified protein can be characterized
      by Western and non-radioactive ligand blots using enhanced chemiluminescence
      (ECL), a non-radioactive ligand blot method using VHDL-FITC is presented, which
      allows for the quick analysis of the receptor directly from the blot under
      standard UV light. Sufficient receptor protein has been derived for amino acid
      analysis, receptor-ligand and xenobiotic binding studies.

PMID- 14965773
TI  - Functional expression and direct visualization of the human alpha 2B -adrenergic
      receptor and alpha 2B -AR-green fluorescent fusion protein in mammalian cell
      using Semliki Forest virus vectors.
AB  - The alpha 2B -adrenergic receptor ( alpha 2B -AR), a member of the G protein
      coupled receptor (GPCR) superfamily, was expressed at high levels from Semliki
      Forest virus (SFV) vectors in mammalian cells. Constructs were engineered by
      fusing enhanced green fluorescent protein (eGFP) and the SFV capsid to opposite
      ends of the alpha 2B -AR. The receptor fusions alpha 2B -AR-eGFP and CAP- alpha
      2B -AR expressed in CHO-K1 cells generated alpha 2B values of 176 and 122pmol/mg
      of membrane protein, respectively, and showed similar ligand binding
      characteristics, alpha 2B -AR subtype-selectivity, and G protein activation as
      reported for stable expression in CHO-K1 cells. Cryo-electron microscopy and eGFP
      based fluorescence indicated the same subcellular receptor distribution. SFV
      expression is well suited for studies on the pharmacology, biochemistry, and cell
      biology of GPCRs, and for large-scale recombinant protein production in mammalian
      suspension culture to generate sufficient receptor quantities for structural
      biology.

PMID- 14965774
TI  - Purification and characterisation of functional early pregnancy factor expressed
      in Sf9 insect cells and in Escherichia coli.
AB  - Early pregnancy factor (EPF) is a secreted protein with growth regulatory and
      immunomodulatory properties. It is an extracellular form of the mitochondrial
      matrix protein chaperonin 10 (Cpn10), a molecular chaperone. An understanding of
      the mechanism of action of EPF and an exploration of therapeutic potential has
      been limited by availability of purified material. The present study was
      undertaken to develop a simple high-yielding procedure for preparation of
      material for structure/function studies, which could be scaled up for therapeutic
      application. Human EPF was expressed in Sf9 insect cells by baculovirus infection
      and in Escherichia coli using a heat inducible vector. A modified molecule with
      an additional N-terminal alanine was also expressed in E. coli. The soluble
      protein was purified from cell lysates via anion exchange (negative-binding
      mode), cation exchange, and hydrophobic interaction chromatography, yielding
      approximately 42 and 36mg EPF from 300ml bacterial and 1L Sf9 cultures,
      respectively. The preparations were highly purified (#10878;99% purity on SDS
      PAGE for the bacterial products and #10878;97% for that of insect cells) and had
      the expected mass and heptameric structure under native conditions, as determined
      by mass spectrometry and gel permeation chromatography, respectively. All
      recombinant preparations exhibited activity in the EPF bioassay, the rosette
      inhibition test, with similar potency both to each other and to the native
      molecule. In two in vivo assays of immunosuppressive activity, the delayed-type
      hypersensitivity reaction and experimental autoimmune encephalomyelitis, the
      insect cell and modified bacterial products, both with N-terminal additions
      (acetylation or amino acid), exhibited similar levels of suppressive activity,
      but the bacterial product with no N-terminal modification had no effect in either
      assay. Studies by others have shown that N-terminal addition is not necessary for
      Cpn10 activity. By defining techniques for facile production of molecules with
      and without immunosuppressive properties, the present studies make it possible to
      explore mechanisms underlying the distinction between EPF and Cpn10 activity.

PMID- 14965775
TI  - Cytoplasmic expression of the Achromobacter xylosoxidans blue copper nitrite
      reductase in Escherichia coli and characterisation of the recombinant protein.
AB  - The gene of the Achromobacter xylosoxidans (DSM 2402) blue copper-containing
      nitrite reductase was amplified using the polymerase chain reaction. DNA sequence
      analysis reveals that the amino acid sequence is identical to those of the
      GIFU1051 and the NCIMB11015 A. xylosoxidans nitrite reductases. The gene encoding
      the mature coding region for DSM 2402 nitrite reductase was cloned into a pET
      vector, overexpressed in the cytoplasm of Escherichia coli BL21(DE3), and the
      expressed holoprotein was purified to apparent homogeneity by cation-exchange
      chromatography. The recombinant blue copper-containing nitrite reductase was
      obtained in high yields of 70mgL(-1) of culture. The specific catalytic activity
      as well as the electronic absorption and electron paramagnetic resonance spectra
      agree with corresponding data for the native protein. Mass spectroscopic analysis
      of the recombinant nitrite reductase gave a molecular weight of 36659.1Da for the
      apo-protein monomer, in agreement with the expected molecular mass based on the
      amino acid sequence.

PMID- 14965776
TI  - Co-expression of a prophage system and a plasmid system in Bacillus subtilis.
AB  - A dual expression system for overexpressing two proteins by a single cell strain
      has been developed in Bacillus subtilis. This dual expression system combines the
      phi105MU331 prophage system and a plasmid system within a single cell. Protein
      expression by the prophage system is heat inducible, while that of the plasmid
      system is constitutive. Three candidate genes, BPN, BT, and amyE, all of Bacillus
      origin, were used as test models. Seven strains (BPN, BT, AMY, BS168K, MU331K,
      BPNK, and BTK) were constructed to investigate the influences of the prophage
      system and the plasmid system on each other, and to compare the efficiency of the
      individual expression systems with that of the dual expression system.
      Individually, the yield of the plasmid system is higher than that of the prophage
      system, which could be attributed to the constitutive nature of the expression of
      the plasmid system. Nonetheless, for the dual expression strains, the expression
      of two enzymes in a single fermentation run can reduce costs in facilities,
      manpower, and utilities. Fed-batch fermentation of BPNK strains confirmed the
      feasibility of applying this dual expression system in industrial-scale
      production.

PMID- 14965777
TI  - Molecular cloning, expression, purification, and mass spectrometric
      characterization of 3C-like protease of SARS coronavirus.
AB  - Severe acute respiratory syndrome (SARS) is an acute respiratory illness, which
      has broken out in China. It has been known that SARS coronavirus (SARS_CoV) is a
      novel human coronavirus and is responsible for SARS infection. Belonging to one
      of the major proteins associated with SARS_CoV, SARS 3C-like protease
      (SARS_3CL(pro)) functions as a cysteine protease engaging in the proteolytic
      cleavage of the viral precursor polyprotein to a series of functional proteins
      required for coronavirus replication and is considered as an appealing target for
      designing anti-SARS agents. To facilitate the studies regarding the functions and
      structures of SARS_3CL(pro), in this report the synthetic genes encoding 3CL(pro)
      of SARS_CoV were assembled, and the plasmid was constructed using pQE30 as vector
      and expressed in Escherichia coli M15 cells. The highly yielded ( approximately
      15mg/L) expressed protease was purified by use of NTA-Ni(2+) affinity
      chromatography and FPLC system, and its sequence was determined by LC/MS with the
      residue coverage of 46.4%.

PMID- 14965778
TI  - Purification and characterization of a recombinant alpha-N
      acetylgalactosaminidase from Clostridium perfringens.
AB  - Clostridium perfringens alpha-N-acetylgalactosaminidase (alphaNAG) hydrolyzed the
      terminal N-acetyl-alpha-d-galactosamine from the blood type A(2) antigen
      producing H antigen, blood type O. Blood type O is universally compatible in the
      ABO system. Purification of the native enzyme is difficult with very low yields.
      To obtain the enzyme in satisfactory yield, the gene encoding the clostridial
      enzyme was cloned in an Escherichia coli T7 expression system. A highly purified
      preparation of recombinant alphaNAG was obtained from cell lysates by ion
      exchange chromatography and high-pressure liquid chromatography. The final
      preparation was homogeneous by SDS-PAGE with a molecular mass of 71.96kDa and the
      native molecular weight of 72.42kDa. The enzyme was highly selective for terminal
      N-acetylgalactosamine residues. No other significant exoglycosidase activities,
      particularly neuraminidase, were detected. The pH optimum of the enzyme was
      between 6.5 and 7.0 and activity was relatively unaffected by ionic strength.
      ELISA experiments demonstrated activity against blood type A(2) epitope. These
      characteristics were similar to those of native alphaNAG from C. perfringens.
      With adequate expression in E. coli, sufficient recombinant alphaNAG enzyme mass
      can be obtained for potential use in enzymatic conversion of human blood type
      A(2) red blood cells to universally transfusable type O red blood cells.

PMID- 14965779
TI  - Expression of N-formylated proteins in Escherichia coli.
AB  - In bacteria, protein expression initiates with a formyl-methionine group.
      Addition of the antibiotic actinonin, a known peptide deformylase inhibitor, at
      the time of induction of protein expression results in the retention of the
      formyl group by the overexpressed protein. In addition, because deformylation is
      a prerequisite for removal of the initiating methionine, this post-translational
      processing step is also prevented by actinonin, and the N-formyl methionine
      residue is retained by proteins from which it is normally removed. We have
      demonstrated the applicability of this system for obtaining N-modified forms of
      several different proteins and use one of these modified molecules to show that
      the N-terminal amino group is not required for ClpXP degradation of proteins
      bearing an N-terminal recognition signal.

PMID- 14965780
TI  - Construction of high-density display of CD147 ectodomain on VCSM13 phage via
      gpVIII: effects of temperature, IPTG, and helper phage infection-period.
AB  - Production of VCSM13 phage displaying a high density of CD147 ectodomain
      (CD147Ex) was achieved when culturing conditions were modulated. A phagemid
      expressing CD147Ex was constructed and used to produce phage display CD147Ex
      gpVIII fusion protein in TG1 Escherichia coli. Displaying of CD147Ex via gpVIII
      was successfully increased when growing the transformed TG1 at 25 degrees C with
      IPTG-stimulation. In addition to temperature and IPTG-stimulation, the VCSM13
      helper phage infection-period particularly affected the insertion of CD147Ex into
      phage progeny. By sandwich ELISA, incorporation of the CD147Ex into phage
      particle was confirmed. The correct size of the CD147Ex-gpVIII fusion protein at
      28kDa was demonstrated by Western immunoblotting. Multivalent display of CD147Ex
      on phage particles will be valuable in discovering its ligand partner.

PMID- 14965781
TI  - Trailer loading stress in horses: behavioral and physiological effects of
      nonaversive training (TTEAM).
AB  - Resistance in the horse to trailer loading is a common source of stress and
      injury to horses and their handlers. The objective of this study was to determine
      whether nonaversive training based on the Tellington-Touch Equine Awareness
      Method (TTEAM; Tellington-Jones &Bruns, 1988) would decrease loading time and
      reduce stress during loading for horses with a history of reluctance to load. Ten
      horses described by their owners as "problem loaders" were subjected to
      pretraining and posttraining assessments of loading. Each assessment involved two
      7-min loading attempts during which heart rate and saliva cortisol were measured.
      The training consisted of six 30-min sessions over a 2-week period during which
      the horse and owner participated in basic leading exercises with obstacles
      simulating aspects of trailering. Assessment showed heart rate and saliva
      cortisol increased significantly during loading as compared to baseline (p <.001
      and p <.05, respectively). Reassessment after training showed a decrease in
      loading time (p <.02), reduced heart rate during loading (p <.002), and reduced
      saliva cortisol as compared to pretraining assessments. Seven "good loaders" also
      were subject to loading assessment for physiological comparison. Increases in
      heart rate during loading were significantly higher in the good loaders (p
      <.001). Nonaversive training simulating aspects of loading may effectively reduce
      loading time and stress during loading for horses with a history of resistance to
      trailer loading.

PMID- 14965782
TI  - Behavioral abnormalities in captive nonhuman primates.
AB  - In this study, we dealt with 11 species of nonhuman primates across 10 zoos in
      India. We recorded behavior as instantaneous scans between 9 a.m. and 5 p.m. In
      the study, we segregated behaviors for analyses into abnormal, undesirable,
      active, and resting. The 4 types of abnormal behavior exhibited included floating
      limb, self-biting, self-clasping, and stereotypic pacing. In the study, we
      recorded 2 types of undesirable behavior: autoerotic stimulation and begging.
      Langurs and group-housed macaques did not exhibit undesirable behaviors. A male
      lion-tailed macaque and a male gibbon exhibited begging behavior. autoerotic
      stimulation and self-biting occurred rarely. Males exhibited higher levels of
      undesirable behavior than did females. Animals confiscated from touring zoos,
      circuses, and animal traders exhibited higher levels of abnormal behaviors than
      did animals reared in larger, recognized zoos. The stump-tailed macaque was the
      only species to exhibit floating limb, autoerotic stimulation, self-biting, and
      self-clasping. Our results show that rearing experience and group composition
      influence the proportions of abnormal behavior exhibited by nonhuman primates in
      captivity. The history of early social and environmental deprivation in these
      species of captive nonhuman primates probably is critical in the development of
      behavioral pathologies. Establishing this will require further research.

PMID- 14965783
TI  - Environmental enrichment for dendrobatid frogs.
AB  - The Central Park Zoo, one of the Wildlife Conservation Society's Living
      Institutions in New York, recently renovated an exhibit for dart-poison frogs.
      Staff developed a new hollow coconut insect feeder in conjunction with this
      project. When the exhibit change, coconut feeder, and other enrichments were
      tested for effectiveness, the coconut feeder enrichment produced the greatest
      increase in frog activity in traditional and new exhibits. This may be due to the
      coconut feeder's relatively complicated nature, which randomizes the release of
      insects into the exhibit. The goal of this project was to help develop a best
      practices approach to dendrobatid husbandry for zoological facilities to use in
      the future.

PMID- 14965784
TI  - Absence of effects from immunocontraception on seasonal birth patterns and foal
      survival among barrier island wild horses.
AB  - Despite a large body of safety data, concern exists that porcine zonae pellucidae
      (PZP) immunocontraception--used to manage wild horse populations--may cause out
      of-season births with resulting foal mortality. Our study at Assateague, Maryland
      indicated the effects of immunocontraception on season of birth and foal survival
      between 1990 and 2002 on wild horses from Assateague Island. Among 91 mares never
      treated, 69 (75.8%) of foals were born in April, May, and June (in season). Among
      77 treated mares, 50 (64.9%) were born in season. Of 29 mares foaling within 1
      year after treatment (contraceptive failures), 20 (68.9%) were born in season. Of
      48 mares treated for greater than 2 years then withdrawn from treatment, 30
      (62.5%) of 48 foals were born in season. There were no significant differences (p
      <.05) between either treatment group or untreated mares. Survival did not differ
      significantly among foals born in or out of season or among foals born to treated
      or untreated mares. Data indicate a lack of effect of PZP contraception on season
      of birth or foal survival on barrier island habitats.

PMID- 14965785
TI  - Do domestic pigs in controlled environments contrafreeload?
AB  - Many experiments report that animals will work (lever press) for food in the
      presence of freely available identical food. This phenomenon has attracted the
      attention of applied ethologists because it seems to prove that animals have a
      need to express appetitive behavior. If this is the case, then it has
      implications for the provision of environmental enrichment for animals in
      captivity. In this experiment, we maintained 6 pigs in closed economy
      environments for three 120-hr choice periods in which they had continuous free
      access to operant and identical free food. In the experiment, we tested pigs
      using 2 different operant schedules, fixed ratio (FR) 5 and variable ratio (VR)
      5. We used a VR schedule because many enrichment studies claim that
      unpredictability is an important characteristic that makes an enrichment device
      attractive. The results show that pigs exhibited a negligible level of
      contrafreeloading (M +/- standard error of the mean proportion = 0.05 +/- 0.01).
      Furthermore, there were no significant differences between FRs and VRs of
      reinforcement.

PMID- 14965786
TI  - Genetically modified laboratory animals--what welfare problems do they face?
AB  - In this article, we respond to public concern expressed about the welfare of
      genetically modified (GM) nonhuman animals. As a contribution to the debate on
      this subject, we attempt in this article to determine in what situations the
      practice of genetic modification in rodents may generate significant welfare
      problems. After a brief discussion of the principles of animal welfare, we focus
      on the problem of animal suffering and review some types of gene modifications
      likely to cause predictable welfare problems. In this article, we also consider
      suffering that may be involved in the process of generating GM animals. Finally,
      we discuss the role of GM animals in attempts to reduce, replace, and refine the
      use of animals in research.

PMID- 14965788
TI  - Physiopathology of acne vulgaris: recent data, new understanding of the
      treatments.
AB  - Acne is the most frequent reason for seeing a dermatologist, but its
      physiopathology is not completely well-known. Yet understanding of the mechanisms
      of action of the different acne treatments is very important to optimize their
      use. A lot of new data on the physiopathology have recently been published in the
      acne field. This paper summarizes the main points of these new facts.

PMID- 14965789
TI  - CLA(+) T cells in cutaneous diseases.
AB  - The Cutaneous Lymphocyte-associated Antigen (CLA) was originally described as a
      cell surface molecule preferentially found on T lymphocytes present in the skin.
      At the present time, a more complete and exciting picture is emerging thanks to
      the efforts of different research groups. The CLA antigen identifies a subset of
      memory effector T lymphocytes functionally involved in the pathogenesis of
      different T cell-mediated cutaneous diseases. Research related to CLA(+ )T cells
      is not only becoming a source of interesting data related to the pathological
      mechanisms of skin disorders, but also provides an innovative and selective
      approach to develop new treatments for T cell-mediated diseases in dermatology.

PMID- 14965790
TI  - Retinoic-acid receptor beta expression in melanocytes.
AB  - Retinoic acid receptors (RAR) and retinoic X receptors (RXR) are critical for
      skin homeostasis. In epidermis, RXRalpha and RARgamma isoforms are highly
      expressed but only weak or no expression of RARbeta has been reported. Here, we
      re-examined RARbeta in situ expression in comparison with that of the RXRalpha,
      in both normal skin and melanocytic tumours. In normal skin, RXRalpha was
      localized in epidermis, sebaceous glands and hair follicles, while RARbeta was
      detectable only in melanocytes and in stratum granulosum. RXRalpha was never
      detected in melanocytic tumours, neither in nevi, nor in melanomas. RARbeta was
      also absent from melanoma cells but was present in nevus cells. These results
      indicate that melanoma are characterised by simultaneous decrease of RARbeta and
      absence of RXRalpha that may be responsible for the RA-resistance of most
      melanoma cell lines.

PMID- 14965791
TI  - Distribution of an antifungal drug, itraconazole, in pathological and non
      pathological tissues.
AB  - An antifungal drug, itraconazole (ITZ) is effective for chromomycosis patients,
      but the distribution of ITZ and its metabolite, hydroxy-intraconazole (OH-ITZ) is
      unclear in pathological tissues. This study investigated how much ITZ and OH-ITZ
      accumulated in the lesional tissues of chromomycosis and non-lesional skin after
      oral treatment with ITZ. We determined the concentrations of ITZ and OH-ITZ in
      the lesional tissues of chromomycosis by Foncecaea pedrosoi and non-lesional skin
      after oral treatment with a total dose of 2.3g of ITZ. ITZ concentration was
      significantly higher in pathological skin than non-pathological skin. The ITZ
      concentration in the lesional tissues was higher in the central site than in the
      marginal site. No difference was seen in the OH-ITZ concentrations among three
      skin parts, the center and the margin in lesional skin, and non-lesional skin
      adjacent to the lesion. This study showed higher concentrations of ITZ in
      pathological tissues than in non-pathological tissues.

PMID- 14965792
TI  - Thickness, medullation and growth rate of female scalp hair are subject to
      significant variation according to pigmentation and scalp location during ageing.
AB  - The biological importance and/or significance of human hair colour is unknown
      even though greying is obviously associated with ageing. In order to further
      characterise hair pigmentation in relation with hair growth variables we
      evaluated 3 scalp sites (top of the head (T): left and right and occipital(O)) in
      12 untreated menopausal women (age range: 49-66 years: average 59.63 +/- 5.66)
      who presented complaining of hair loss and/or diffuse alopecia. Controls were 12
      non menopausal sexually mature woman (7 age range 15-21 and 5 age range 38-48)
      not complaining of hair loss. One hair sample (whenever possible n = 60) was
      taken one month after clipping from T and O on each person; menopausal women were
      sampled twice. The following measures were performed with a light microscope:
      diameter (average min-max., microm), medulla (0% = absent to 100% = fully
      developed) and linear hair growth rate (mm/day). The hairs were categorised as
      pigmented (P) or non-pigmented (white, W) as compared with a black and white
      reference card. A total of 3343 hairs were analysed with 2-factor analysis of
      variance (ANOVA). A global comparison (all hairs) showed that the average
      diameter of W hair (67.68 microm) exceeded that of P hair (57.41 microm) (p =
      0.0001) and this was maintained on all 3 scalp sites. In addition, the medulla of
      W hair (23.91%) appeared more developed than the medulla of P hair (12.21%) (p =
      0.0001) and was more expressed in W T hairs as compared with W O hairs (p =
      0.0325). There was also a significant interaction between site and pigmentation
      (p = 0.0074). Growth rate of W hairs (0.38 mm/d) was higher than that of P hairs
      (0.35 mm/d) (p = 0.0001) and there was a significant variation according to scalp
      sites (p = 0.0001). There was also a significant interaction between site and
      pigmentation (p = 0.0062) with the following rank order: O W (0.40 mm/d), T W
      (0.37 mm/d), O P (0.37 mm/d) and T P (0.34 mm/d). Subgroups of W and P of paired
      thickness in the range of 50 to 80 pm consistently showed a 10% faster growth
      rate of W. Previous studies have shown that growth rate and diameter declines in
      age and alopecia i.e. in hair thinning. Our data shows that the reduced growth
      rate of terminal hairs is in fact limited to the pigmented hairs. The mechanisms
      by which white hairs are spared these ageing changes are not yet understood. Less
      pigmented hairs are usually undetected by photo- graphic techniques used for drug
      trials. The potential role of drug induced modifications of hair pigmentation
      should be taken into account during the interpretation of efficacy except if
      contrast-enhancement has been applied.

PMID- 14965793
TI  - Interferon-gamma in alopecia areata.
AB  - Alopecia areata is a common type of hair loss. In clinical practice most patients
      will present with reversible patchy hair loss whereas others may develop complete
      baldness. Although the etiopathogenesis of alopecia areata is poorly understood,
      evidence is accumulating that it can be regarded as a T-cell mediated tissue
      restricted autoimmune disease of the hair follicle, especially expressing the T
      helper-type 1 cytokines interleukin-1beta, interleukin-2, and interferon-gamma.
      The aim of the study was to compare the serum levels of interferon-gamma in
      patients with alopecia areata and the control group and also to investigate the
      difference between the localized form of the disease with the extensive forms
      like alopecia totalis (AT) and alopecia universalis (AU). Forty patients with
      alopecia areata and 20 healthy controls were enrolled in the study. Nineteen
      patients had localized AA (LAA) and twenty-one patients had AT, AU or AT/AU. The
      serum levels of interferon-y were measured using enzyme immunoassay techniques.
      The mean serum IFN-gamma level in AA patients (n = 40) was 14.25 +/- 8.76 pg/mL
      (mean +/- SD), whereas that of LAA (n = 19) or extensive (AT, AU or AT/AU) (n =
      21) was 13.45 +/- 6.75 pg/mL or 14.98 +/- 10.37 pg/mL, respectively. The mean
      serum IFN-gamma level in controls was 9.95 +/- 2.6 pg/mL. Serum levels of IFN
      gamma in patients with AA were significantly higher than those in controls (p <
      0.05). Significant difference was observed in serum levels of IFN-y between
      patients with LAA and control group (p < 0.05). Serum levels of IFN-gamma in
      patients with AT, AU or AT/AU were significantly higher than those in controls (p
      < 0.05). There was no significant difference in levels of IFN-gamma between
      patients with LAA and extensive group (p > 0. 05). We conclude that the elevated
      serum levels of IFN-gamma may reflect the inflammatory symptoms in AA, especially
      in the extensive form and that control of IFN-gamma production may be important
      to management of this disease. And also the measurement of serum IFN-gamma in
      patients with AA may be useful in discriminating those likely to progress to AU
      from the remaining LAA, or as a prognostic indicator.

PMID- 14965794
TI  - Hemorrhagic Kaposi sarcoma. Successful treatment with IFN-alpha.
AB  - A 76-year-old woman with atypical hemorrhagic Kaposi sarcoma is presented. The
      patient was treated with recombinant interferon alpha-2b (3,000,000 IU)
      subcutaneously, three times weekly for 6 months and twice weekly as maintenance
      dose for 14 months with excellent response and no recurrence after a 7 years of
      follow-up.

PMID- 14965795
TI  - Alefacept: a novel and selective biologic agent for the treatment of chronic
      plaque psoriasis.
AB  - Psoriasis is a chronic immune-mediated disease affecting the skin and sometimes
      the joints. Approximately 14 million people in Europe have psoriasis and the
      disease has a profound effect on the quality of life of patients worldwide.
      Currently available therapies for psoriasis have several shortcomings, including
      organ-based toxicity, generalized immunosuppression, short duration of response,
      and inconvenient regimens. Alefacept is a recombinant, fully human fusion protein
      that selectively targets the memory T cell population implicated in psoriasis
      pathogenesis. Alefacept is unique among psoriasis treatments because of its
      selective therapeutic action, ability to induce lengthy disease remissions even
      in the absence of continued therapy, positive effect on quality of life, and
      favorable safety profile. Two courses of alefacept confer greater efficacy and
      duration of clinical improvement versus that observed with a single course. This
      novel biologic agent is currently approved in the United States and under
      regulatory review in Europe for moderate to severe chronic plaque psoriasis.

PMID- 14965796
TI  - Autologous transplantation techniques for vitiligo: how to evaluate treatment
      outcome.
AB  - Effective methods for measuring treatment outcome in vitiligo are essential to
      accurately assess possible therapeutic modalities. This systematic review article
      aims to bring the problems concerning evaluation of treatment outcome in vitiligo
      studies using transplantation techniques to the attention of clinical
      investigators. Furthermore we highlight the interpretation of the achieved result
      from both physicians' and patients' view point using a questionnaire put to 558
      dermatologists and 152 vitiligo patients in Belgium. There is no consensus about
      the choice of an evaluation method in surgical vitiligo studies. The
      interpretation of a 'successful' treatment result seemed to differ among
      dermatologists and vitiligo patients. We conclude that further research is needed
      to develop a universally accepted, objective, reliable and useful measurement
      method to evaluate the efficacy of surgical vitiligo treatments. A combination of
      both a clinical and a psychological measurement is likely to be the most
      appropriate choice.

PMID- 14965797
TI  - Polymerase chain reaction in the diagnosis of onychomycosis.
AB  - Onychomycosis is a mycotic infection of the nail which accounts for 50% of all
      nail disorders. However, there is no predictably successful diagnostic approach
      to onychomycosis. The aim of this study was to demonstrate the feasibility of
      polymerase chain reaction (PCR) in diagnosis of onychomycosis and compare it with
      microscopy and culture. Fifty-two patients with clinically suspected
      onychomycosis were included in this study. After a sufficient amount of specimen
      was taken from the nail, PCR, microscopy and cultural methods were used in the
      examination of the samples. Out of all the 52 specimens, 40 (77%) specimens were
      positive by microscopy, 12 (23%) by culture, and 20 (38%) by PCR. In conclusion,
      if enough material can be taken, the PCR method appears to be a valuable
      diagnostic tool in cases where fungus can not be detected by conventional
      methods.

PMID- 14965798
TI  - Wound healing of chronic leg ulcers under the influence of erysipelas.
AB  - We report four patients with long-lasting therapy-resistant ulcus cruris, on
      which a new erysipelas was superimposed. In one case there was a total closure of
      the ulcers under the erysipelas. In three patients a reduction in size occurred.
      All ulcers became flatter. Other stimuli of wound healing were excluded. Because
      of the long-lasting existence and well known therapy resistance in each case,
      these changes suggest a positive effect of the erysipelas on the healing of the
      ulcers. We assume that serum cytokines could offer a possible explanation for
      this. The concentrations of the IL-6 and IL-2-receptor were initially raised and
      then later decreased in three of the four cases. Because of the complex
      stimulation and regulation mechanisms in the cytokine network which are triggered
      by inflammation, systemic and local effects of keratinocytes,
      monocytes/macrophages, fibroblasts and endothelium cells could also be assumed to
      support wound healing.

PMID- 14965799
TI  - Emerging imported parasitoses in Italy.
AB  - In the period 1987-2001, 111 cases of imported parasitoses were diag- nosed in
      three Italian dermatology departments (Monza, Milan and Siena): 22 cases of
      tungiasis, 11 of furuncular myiasis and 78 of creeping eruption. The patients
      were 73 males and 38 women, who had been on trips abroad. All underwent
      appropriate treatment and recovered. Here we describe the geographic location of
      the parasites, the clinical features of the skin manifestations and differential
      diagnoses. Autochthonous cases of these infections, which are increasingly
      frequent as Europeans travel to endemic areas, have been described. Detailed
      knowledge of these parasitoses is necessary to enable prompt diagnosis and
      treatment.

PMID- 14965800
TI  - Health-related quality of life among patients with ichthyosis.
AB  - Ichthyosis encompasses a heterogeneous group of hereditary skin disorders, which
      can be present at birth or develop in childhood. The aim of the present study was
      to investigate the Health related quality of life (HRQoL) of patients with
      ichthyosis. Two questionnaires (Dermatology Life Quality Index [DLQI], and the
      generic Short Form [SF] - 36) and a subjective measure of disease activity
      employing a visual analogue scale (VAS) were mailed to 144 patients. 122 patients
      aged 17-78 years responded. The median for DLQI was 5.0, which was significantly
      higher (worse) for Lamellar ichthyosis than for X-linked recessive ichthyosis.
      The SF-36 showed significantly lower (worse) scores for the study group in four
      of the eight dimensions compared to age- and gender-adjusted Swedish norm scores.
      No differences in SF-36 were found between men and women or between the different
      groups of ichthyosis. The results demonstrate that ichthyosis has an adverse
      effect on HRQoL.

PMID- 14965801
TI  - Transverse leukonychia in severe hypocalcemia.
AB  - We report the case of a 26-year-old man with acral tetany and muscular cramps of
      the upper limbs associated with hypocalcemia caused by hypoparathyroidism and
      celiac disease. Physical examination revealed a transverse leukonychia which
      disappeared after treatment with calcium lactogluconate, calcium carbonate and
      calcitriol. Hypocalcemia may induce nail alterations with a double mechanism
      represented by angiospasm and disorganization of the hard keratin and of the
      integrin subunits.

PMID- 14965802
TI  - Photoallergic hand eczema due to benzydamine.
AB  - Hand eczema is a very frequent pathology in Dermatology. We report the case of a
      65-year-old woman who developed a photoallergic eczema on her hands due to
      benzydamine present in her gynecological washing solution. It is probably an
      under-diagnosed cause of hand dermatitis. It also draws attention to the
      importance of a good anamnesis in dermatology.

PMID- 14965803
TI  - Treatment of an infantile acne with oral isotretinoin.
AB  - We report the case of a little girl who presented with a nodulocystic acne which
      had its onset at the age of 20 months. She had no clinical or biological features
      of endocrinopathy. The lesions did not respond to conventional antibiotics so she
      was started on oral isotretinoin. A seven-month treatment period was necessary to
      achieve remission. The onset of infantile acne is usually around 6 to 16 months
      and there is a male predominance. The onset is later in females. Oral
      erythromycin is the first line treatment when topical therapies are
      inefficacious. Some cystic lesions do not respond to oral antibiotics. In these
      cases, oral isotretinoin may be effective and the treatment is similar to that of
      an adult. Clinical and biological tolerance is good with no growth retardation.
      Lesions may relapse after the withdrawal of isotretinoin but they are less
      important and easily controlled with topical treatments. Isotretinoin can be used
      for nodulocystic acne to reduce the risk of scarring.

PMID- 14965804
TI  - Eczema molluscatum in tacrolimus treated atopic dermatitis.
AB  - Eczema molluscatum describes the occurrence of molluscum contagiosum virus
      infection in a patient with underlying atopic dermatitis. Novel, safe and
      effective treatment options in atopic dermatitis are the topical immunomodulators
      tacrolimus and pimecrolimus. One major advantage over corticosteroids is that
      they do not induce skin atrophy. Some physicians fear that topical
      immunomodulators may predispose patients to skin infections. We observed a
      patient with atopic dermatitis who developed eczema molluscatum during treatment
      with tacrolimus 0.1% ointment. After withdrawal of tacrolimus, the lesions
      resolved spontaneously over 3 weeks.

PMID- 14965805
TI  - Non-allelic twin spotting under attack.

PMID- 14965806
TI  - Risk factors for graft survival in sensitized recipients of kidney
      transplantation.
AB  - OBJECTIVE: To investigate the independent prognostic factors for graft survival
      in sensitized recipients undergoing kidney transplantation, so as to identify the
      individuals at high risk of graft loss before transplantation. METHODS: A
      retrospective investigation was conducted in 102 sensitized kidney transplant
      recipients and 31 relative variables were analyzed with SPSS10.0 software. Using
      log-rank method, the influence of these variables on short- and long-term graft
      survivals was evaluated, and Kaplan-Meier analysis was performed to estimate the
      1-, 3- and 5-year graft survival rates and half-life. Proportional hazards
      regression analysis (Cox model) was used to assess the relative risks of the
      potential variables. RESULTS: In the recipients with a mean half-life of 8.9
      years, the 1-, 3- and 5-year graft survival rates were 90%, 85%, and 75%,
      respectively. By log-rank analysis, the factors affecting short- and long-term
      graft survivals were identified, namely the recipient age, times of
      transplantation, levels of panel reactive antibody and the post-operative anti
      HLA-IgG antibody, HLA mismatch, renal function, time needing for graft function
      recovery, presence of acute rejection, delay of graft function recovery and
      infection, which affected the graft survival demonstrated by Cox model
      multivariate analysis. CONCLUSION: High-quality donor kidney and minimization of
      the risk factors for graft survival may insure successful kidney transplantation
      in sensitized recipients.

PMID- 14965807
TI  - Immunosuppression induction with daclizumab and antithymocyte globulin in cardiac
      transplantation: clinical experience with 8 cases.
AB  - OBJECTIVE: To review the clinical experience of immunosuppression induction
      therapy to prevent acute rejection in 8 patients with cardiac transplant.
      METHODS: Between June, 2000 and May, 2002, 8 patients with end-stage dilated
      cardiomyopathy undergoing orthotopic cardiac transplantation received induction
      therapy with two-dose daclizumab (1.0 mg/kg), given intravenously within 12 h
      before cardiac-transplantation surgery and two weeks thereafter, and with an
      initial 5-day course of intravenous antithymocyte globulin (100 mg/d) following
      transplantation. Cyclosporine or tacrolimus, mycophenolate mofetil or
      azathioprine, and prednisolone were applied for immunosuppression maintenance.
      RESULTS: No death occurred during the follow-up. Routine endomyocardial biopsies
      in all cases performed in the early stage detected only mild rejection, and no
      acute allograft or renal dysfunction was found. Three patients developed
      opportunistic infection, and only one had late acute rejection in the 14th post
      transplantation month. CONCLUSIONS: Induction therapy with intravenous daclizumab
      and antithymocyte globulin is effective to prevent acute rejection and alleviate
      organ dysfunction in cardiac transplantation, but might increase the chance of
      infections.

PMID- 14965808
TI  - Preparation of monoclonal antibodies against different epitopes on extracellular
      domain of human receptor for advanced glycation end product.
AB  - OBJECTIVE: To prepare and characterize monoclonal antibodies (mAb) against
      recombinant human receptor for advanced glycation end product (rhRAGE). METHODS:
      BALB/c mice were immunized with recombinant extracellular domain  amino acid 23
      342   of human advanced glycation end product (RAGE), and hybridoma was generated
      with mouse spleen cells and myeloma NS-1 cells. After three fusions and cloning,
      two hybridoma cell lines secreting monoclonal antibodies to RAGE were obtained
      and monoclonal antibodies were purified from the ascites followed by
      characterization with indirect enzyme-linked immunosorbent assay (ELISA), flow
      cytometry and Western blotting. RESULTS AND CONCLUSION: Two hybridoma cell lines
      secreting anti-RAGE mAb were established and designated as B2.2 and E10,
      respectively. Both of mAb B2.2 and E10 belonged to IgG2b isotype and could bind
      to recombinant RAGE and natural RAGE expressed on THP-1 cells. In addition, B2.2
      and E10 could recognize different epitopes of RAGE, which were conformed to be
      capable of detecting soluble recombinant RAGE in sandwich ELISA. These two mAbs
      against different epitopes of rhRAGE would be useful for study of glycation end
      product and RAGE-related diseases.

PMID- 14965809
TI  - A fast sequential image fractal coding approach based on optimal fuzzy
      clustering.
AB  - To reduce the coding time of the conventional method, a fast sequential image
      fractal compression algorithm was proposed on the basis of the principle of
      optimal fuzzy clustering (OFC) for an unsupervised sample set with the category
      number settled by the algorithm itself. We utilized the cost function defined by
      the OFC algorithm to obtain the best category number corresponding to the minimum
      value of the function. Firstly the Linde-Buzo-Gray (LBG) algorithm was realized
      to acquire a rough cluster of the domain pool. Then the optimal category number
      was obtained by implementing our algorithm with small computational cost. Finally
      the more precise category was gained and the detail of the reconstructed image
      efficiently preserved. As a global optimal algorithm, OFC not only helps LBG
      eliminate the local minima, but also effectively compensates for the arbitrary
      interference in hard clustering problem. Soft clustering of the domain blocks
      allows classified searches instead of global ones and takes less coding time, and
      therefore clearly outperforms to the classic method relying on reduction of the
      size of the domain pool by classification. In computer simulation, OFC-based
      algorithm for the fractal coding scheme achieved excellent performance. For some
      standard and sequential medical images, the results denoted that the encoding
      speed was improved by about 5 folds without affecting the signal-to-noise ratio
      and compression ratio, and the quality of the reconstructed image could be better
      retained.

PMID- 14965810
TI  - Killing effect of suicide gene system under control by KDR promotor on human
      umbilical vein endothelial cells.
AB  - OBJECTIVE: To study the killing effect of adenovirus-mediated double suicide gene
      under the regulation of kinase domain-containing receptor (KDR) promoter on human
      umbilical vein endothelial cells (HUVECs). METHODS: The sequences of human KDR
      promoter gene, CD gene and TK gene were amplified by PCR, and the plasmid pKDR
      CDglyTK was constructed. A two-step transformation protocol was employed for the
      construction of a recombinant adenoviral plasmid pAdKDR-CDglyTK that was
      transfected into 293 packaging cells to further multiply and purify the
      adenovirus. HUVECs were infected by the resultant recombinant adenovirus of
      different multiplicities of infection (MOI), and the infection rate was measured
      by observing the expression of green fluorescence protein (GFP). The infected
      cells were cultured in the culture media containing ganciclovir (GCV) and/or 5
      fluorocytosine (5-FC) at different concentrations, and the killing effects were
      evaluated. RESULTS: Recombinant adenovirus AdKDR-CDglyTK were successfully
      constructed, which could efficiently infect HUVEC cells, with the infection rate
      associated with the MOI of the recombinant adenovirus. HUVEC cells infected with
      AdKDR-CDglyTK were highly sensitive to the prodrugs, their survival rate
      correlated to both the concentration of the prodrugs and the MOI of the
      recombinant adenovirus. The killing effect of the two produrgs used in
      combination was much stronger than that of exclusive use of GCV or 5-FC.
      CONCLUSIONS: Prodrug/KDR-CdglyTK system is effective in killing HUVEC cells, and
      its killing effect is correlated with the concentration of the prodrugs and the
      MOI of the recombinant adenovirus. Combination of the two prodrugs produces
      stronger killing effect on the cells.

PMID- 14965811
TI  - Effect of SOD and NaHCO3 on the vascular hyporeactivity of rats after severe
      hemorrhagic shock.
AB  - OBJECTIVE: To investigate the effect of SOD and NaHCO3 on the vascular
      hyporeactivity after severe hemorrhagic shock in rats. METHODS: Twenty eight
      Sprague-Dawley rats were divided randomly into 4 groups of 7 each: SOD-treated
      group, NaHCO3-treated group, SOD+NaHCO3-treated group  and normal saline-treated
      control group. The responses of arterioles to norepinephrine (NE), the effects of
      dopamine on blood pressure, blood flow velocity in arterioles, the mean arterial
      pressure (MAP), and the survival time within 24 h were measured. RESULTS: Two
      hours after shock, the arteriolar vasoreactivity was significantly reduced and
      threshold concentration of NE was increased by 24 to 27 folds. After beting
      treated separately with SOD, NaHCO3 and SOD+NaHCO3, arteriolar vasoreactivity was
      restored to some extent, among which the SOD+NaHCO3 group obtained a most
      significant effect with decreased threshold concentration of NE to 21% of its
      normal level. In SOD+NaHCO3-treated group, injection of dopamine indicated a most
      significant effect on MAP with 1.9 times more than that in control group, and the
      enhanced MAP was maintained at a level of more than 13.33 kPa after reinfusion of
      shed blood. The blood flow in arteriole was 2.54-fold higher than that in control
      group after 2 h resuscitation. The average survival time in SOD+NaHCO3- treated
      group was 2.9 times longer than that in control group. CONCLUSIONS: SOD and
      NaHCO3 could both recover the lower vasoreactivity and increase the enhancing
      effect of dopamine on blood pressure of rats in severe hemorrhagic shock,
      suggesting that coadministration of SOD and NaHCO3 could be a new approach to the
      treatment of severe hemorrhagic shock.

PMID- 14965812
TI  - Clinical evaluation of abdominal multiorgan transplantation.
AB  - OBJECTIVE: To evaluate the clinical effect of abdominal multiorgan
      transplantation in patients with multiorgan failure. METHODS: Simultaneous kidney
      pancreas transplantation (SKPT) with enteric drainage of pancreatic exocrine
      secretions was performed in 2 patients with type 1 diabetes and end-stage renal
      disease. A combined liver-kidney transplantation (CLKT) was done in a 66-year-old
      patient with alcoholic liver cirrhosis and uremia. Simultaneous orthotopic liver
      and heterotopic pancreas-duodenum transplantation (SLPT) was performed in a
      patient with hepatitis B, hepatocirrhosis, hepatic cellular cancer, and type 1
      diabetes. RESULTS: The function of kidney grafts became normal 5 days
      postoperatively and insulin-independent after treatment with low dose insulin for
      10 days in the 2 SKPT patients. For the CLKT patient, both transplanted organs
      rapidly achieved normal functions after operation but suffered-acute liver graft
      rejection on postoperation day 10 and the rejection was controlled after
      methylprednisolone pulse therapy. In the SLPT patient, insulin was withdrawn 5
      days after operation, liver allograft function recovered well. All the patients
      are alive with stable allograft function after following-up for 29, 26, 9 and 6
      months, respectively. CONCLUSIONS: Abdominal multi organ transplantation was
      effective therapy to patients with multiple organ failure. SLPT can reduce acute
      pancreas rejection and promote the recovery of liver allograft.

PMID- 14965813
TI  - Rectal temperature changes of Wistar rats with second-degree scald burn in hot
      and humid environment following immediate cooling therapy.
AB  - OBJECTIVE: To observe the changes in rectal temperature (Tr) after immediate
      cooling therapy for Wistar rats with superficial second-degree scald burn in hot
      and humid environment, and evaluate the effect of the dressing material for
      cooling. METHODS: Twenty-four Wistar rats were randomly divided into 4 groups
      (n=6), namely normal temperature control (NTC), normal temperature cooling
      therapy (NTCT), hot and humid control (HHC), and hot and humid cooling therapy
      (HHCT) groups. Superficial second-degree scald burns were induced in the rats,
      followed by interventions with cooling therapy in the two therapy groups at dry
      bulb temperature (Tdb) of 35.33+/-0.35 degrees Celsius with relative humidity of
      70.81%+/-1.38%, whereas the two control groups were treated at Tdb of 26.33+/
      1.29 degrees Celsius with relative humidity of 71.05%+/-4.57% without dressing
      for cooling therapy. The exposure time of each group was 120 min, and the Tr was
      recorded every 20 min. RESULTS: On the basis of comparisons between the
      measurements taken at 7 different time points, we found that the Tr of the rats
      was elevated in hot and humid environment (P<0.001) and decreased when cooling
      therapy was applied (P<0.001). Interactions between the environmental temperature
      and cooling therapy were noted in their influence on Tr (P=0.003). As the
      exposure time was prolonged, Tr slowly decreased in NTC group, mildly fluctuated
      in NTCT group, but elevated in HHC and HHCT groups with gradual increase of the
      differences between the measurements taken at the same time point. CONCLUSION:
      Application of the dressing material on the abdomen for cooling therapy can
      efficiently lower the Tr, which may prevent the progression of the heat injury.

PMID- 14965814
TI  - Establishment of transgenic mouse model carring the promoter of plunc sequence.
AB  - OBJECTIVE: To construct the vector using specific nasopharynx tissue promoter
      plunc to establish transgeneic mouse model. METHODS: Plunc-EGFP plasmid was
      digested with XhoI, the purified linearized DNA fragments were recovered by gel
      extraction and diluted to the final concentration of 4 microg/ml, before
      introduced into fertilized one-cell mouse eggs by pronuclear microinjection.
      RESULTS: Thirteen founder mice were obtained, 12 of which were positive for the
      integrated EGFP gene as detected by PCR, and 3 were positive shown by Southern
      blotting. CONCLUSION: Specific nasopharynx tissue promoter plunc can effectively
      induce exogenous gene integration into the mouse genome.

PMID- 14965815
TI  - Effects of recombinant Sagartia rosea cytolysin and Lapemis hardwickii
      phospholipase A2 on adventitial fibroblasts proliferation.
AB  - OBJECTIVE: To observe the effects of recombinant Sagartia rosea cytolysin (rSrc)
      and Lapemis hardwickii phospholipase A2(rPLA2) on adventitial fibroblasts
      proliferation. METHODS: NIH-3T3 cells were cultured and treated with rSrc and
      rPLA2 at different concentrations for observation of cell proliferation using non
      radioactive MTS/PES assay in comparison with the control group. RESULTS: The
      ratio of cell proliferation was 0.840+/-0.061 in the control group, and was
      0.263+/-0.044, 0.418+/-0.054, 0.605+/-0.063, 0.772+/-0.054 and 0.906+/-0.072 in
      rSrc groups corresponding to rSrc concentrations of 100, 10, 1 microg/ml and 100,
      10 ng/ml respectively. rSrc was found to significantly inhibit fibroblast
      proliferation in a dose-dependent manner when the concentration used was above 1
      microg/ml (P<0.05), as compared with the control group (P<0.05). The ratio of
      cell proliferation was 0.498+/-0.076, 0.937+/-0.112 and 0.978+/-0.145 in rPLA2
      groups corresponding to rPLA2 concentrations of 100, 10, 1 microg/ml
      respectively, indicating that rPLA2 also significantly inhibited fibroblast
      proliferation at the concentration of 100 microg/ml (P<0.05). CONCLUSION: rSrc
      and rPLA2 can both significantly inhibit adventitial fibroblast proliferation.

PMID- 14965816
TI  - Preparation and characterization of polybutylcyanoacrylate magnetic
      nanoparticles.
AB  - OBJECTIVE: To Prepare and characterize polybutylcyanoacrylate (PBCA) magnetic
      nanoparticles. METHODS: The suspension of PBCA magnetic nanoparticles was
      prepared by emulsion polymerization method. The particle size, size distribution,
      polydispersity and other parameters were determined by photon correlation
      spectroscopy and transmission electron microscopy, and the iron content in the
      nanoparticles by ultraviolet spectroscopy. RESULTS: The data of the particle size
      and size distribution of aqueous decanoic acid stabilized Fe3O4 magnetic fluids
      were acquired, and the influences of concentrations of butylcyanoacrylate (BCA)
      and Dextran-70 on the particle size and size distribution of PBCA magnetic
      nanoparticles were characterized. CONCLUSION: We have for the first time
      successfully prepared stable suspension of PBCA magnetic nanoparticles by
      emulsion polymerization method at pH 6.3-6.4 in aqueous medium.

PMID- 14965817
TI  - Two-step transformation for highly efficient construction of a replication
      defective recombinant adenoviral vector.
AB  - OBJECTIVE: To efficiently construct a replication-defective recombinant
      adenoviral vector using a two-step transformation procedure. METHODS: Plasmid
      pAdEasy-1 was linearized and transformed into E.coli BJ5183 to construct
      BJ5183pAdEasy-1 cells. Cytosine deaminase (CD) gene was obtained from plasmid pBS
      CD, and subcloned into the shuttle plasmid to form transfer plamid of pAdtrackCMV
      CD, which was then linearized and transformed into BJ5183pAdEasy-1 cells. The
      recombinant adenovirus plasmid DNA was extracted from the transformed bacteria
      and digested with Pac I after identification, followed by transfection into 293
      packaging cells. PCR was used to detect target gene, and the titer and the
      infection rate of the recombinant Ad were measured with the aid of green
      fluorescent protein (GFP) reporter gene. The same recombinant AdCMV-CD was
      constructed in a one-step transformation method for comparison. RESULTS: The
      homologous recombination of the two-step transformation method resulted in a
      success rate of 76.5% (13/17), while the success rate of the one-step method was
      only 11.8% (2/17), showing significant difference between the two methods
      (P=0.000 17 by Fisher's exact test). CONCLUSION: The two-step transformation
      procedure is more efficient and convenient than one-step method.

PMID- 14965818
TI  - Calcium signaling events in Streptococcus pneumoniae invasion of human type II
      pneumocytes.
AB  - OBJECTIVE: To study whether Streptococcus pneumoniae (S.pn) can provoke
      filamentous actin (F-actin) rearrangements in vitro through calcium signaling
      pathways in type II pneumocytes(A549 cells), resulting in S.pn invasion of the
      cells. METHOD: After FITC-phalloidin labeling of F-actin, F-actin rearrangements
      were observed by S.pn adhesion to type pneumocyte A549 cells. S.pn invasion of
      A549 cells was determined by pretreating A549 cells with cytochalasin D. To
      investigate whether F-actin rearrangements could be blocked by Ca2+ inhibitors,
      A549 cells were pretreated with Ca2+ inhibitors dantrolene, and loaded in Fura
      2/AM probe to determine the concentration of cytosolic free calcium by S.pn
      adhesion to A549 cells after 30, 60, and 90 min respectively. RESULTS: Intact
      S.pn can promote F-actin rearrangements. Cytochalasin D was able to prevent S.pn
      invasion of A549 cells. No invasion of A549 cell can be determined at 0.25
      microg/ml of cytochalasin D. One subset of the inhibitors of Ca2+ signal
      transduction molecules blocked F-actin rearrangements dose-dependently, and S.pn
      adhesion of A549 cells for 30, 60, and 90 min increased cytosolic free calcium,
      reaching   487.5+/-38.1  ,  548.2+/-35.6   and  557.2+/-47.5   nmol/L,
      respectively. They were higher than of the control group. CONCLUSION: S.pn can
      provoke F-actin rearrangements through Ca2+ signaling pathways, which further
      leads to S.pn invasion of A549 cells.

PMID- 14965819
TI  - Establishment of the methods for searching eukaryotic gene cis-regulatory
      modules.
AB  - On the basis of the knowledge of eukaryotic gene regulation, we modified the
      method in three aspects: (1) Searching the cis-regulatory modules (CRM) according
      Fasta or Blast sequence with multiple sequence and low E value, followed by
      mutual scoring of these sequence with Smith-Waterman algorithms and finally by
      clustering analysis; (2) Searching the transcription factor-binding site using
      International Union of Pure and Applied Chemistry, Position-Weight Matrix(PWM)
      and Dyed method; (3) Designing and implementation of data analysis based on the
      software in Windows 2000 and UNIX using object-oriented technology. The results
      of analysis of the major histocompatibility complex gene family show that this
      procedure may accurately locate the regions that contain some of the CRMs.

PMID- 14965820
TI  - Association of the expressions of platelet-derived growth factor receptor and c
      Fos with the biological characteristics of bladder cancer.
AB  - OBJECTIVE: To elucidate the relation of platelet-derived growth factor receptor
      (PDGFR) and c-Fos protein expressions with human bladder transitional epithelial
      cell carcinoma (BTCC). METHODS: The expressions of PDGFR and c-Fos were
      investigated in 11 normal bladder tissue samples, 14 adjacent non-carcinoma
      tissues and 43 BTCC tissues by means of SP immunohistochemical technique.
      RESULTS: The c-Fos expression was found in the cell nuclei and cytoplasm, and
      PDGFR in the nuclear membrane, cytoplasm, and cellular membrane. PDGFR and c-Fos
      were detected in 81.40% and 48.83% of the BTCC tissues respectively, at the rates
      both significantly higher than those in normal and adjacent non-carcinoma tissues
      (P<0.05). Correlation between the expression of c-Fos and the tumor grading was
      noted (P<0.05). The expressions of PDGFR and c-Fos in tumor blood vessels were
      significantly higher than those in normal vessels. CONCLUSIONS: The expressions
      of PDGFR and c-Fos might be involved in the development of BTCC, possibly related
      to the angiogenesis of the tumors. c-Fos expression can indicated the cell
      proliferative status of the BTCC.

PMID- 14965821
TI  - Design and preparation of oligonucleotide microarray for vaccinia virus
      detection.
AB  - OBJECTIVE: To study the preparation of oligonucleotide microarray for detecting
      vaccinia virus. METHODS: Oligonucleotide probes were designed and synthesized
      according to the specific genes of vaccinia virus. Sample DNA of the virus and
      the negative control sample were obtained and labeled by restriction display
      technique, followed by hybridization to the oligonucleotide microarray and
      scanned by Agilent scanner. RESULTS: Strong hybridization signals were detected
      from the viral DNA hybridized with the microarray, but were absent in the
      negative sample when positive probes were not used. CONCLUSION: Distinct
      differences in the hybridization signals between the virus sample and negative
      sample and between the samples obtained in different phase of infection
      demonstrate high specificity and sensitivity of the microarray for vaccinia virus
      detection.

PMID- 14965822
TI  - Experimental study of the inhibitory effect of indomethacin on the growth and
      angiogenesis of human colon cancer xenografts.
AB  - OBJECTIVE: To evaluate the efficacy of nonsteroidal anti-inflammatory drug
      indomethacin on tumor growth and microvessel angiogenesis of human colon cancer
      xenografts in nude mice. METHODS: Human colorectal cancer HCT116 cells were
      inoculated subcutaneously into BALB/c-nu/nu mice. After daily treatment with oral
      indomethacin for 4 weeks (3 mg.kg-1.d-1), the mice were sacrificed by cervical
      dislocation, and immunohistochemical staining was employed to determine
      microvessel density (MVD) and expression of vascular endothelial growth factors
      (VEGF) in the tumor tissues. RESULTS: Growth of HCT116 tumor was significantly
      suppressed by indomethacin. The tumor volume (mm3) was 458.89+/-32.07 in the
      treated group versus 828.21+/-31.59 in the control group (P<0.05). The MVDs of
      the treated and control groups were 19.50+/-5.32 and 37.40+/-4.93 respectively
      (P<0.001), and VEGF expressions were 1.19+/-0.17 and 1.90+/-0.48 (P<0.01),
      respectively. MVD and VEGF expression in the treated tumor tissue declined
      noticeably as compared with the controls. There was a positive correlation
      between the decrease of VEGF expression and that of MVD (rs=0.714, P<0.05). No
      obvious toxicity was observed in nude mice. CONCLUSION: Indomethacin can inhibit
      the growth of transplanted human colorectal HCT116 tumor in association with a
      significant reduction in angiogenesis, which may be achieved through inhibition
      of VEGF.

PMID- 14965823
TI  - Analysis of the quality of coding for tumors in line with International
      Classification of Diseases.
AB  - OBJECTIVE: To find a method for improving the quality of coding for malignant
      tumors according to the International Classification of Diseases (ICD) and
      explore the feasibility and necessity of such a method. METHODS: The author
      collected 26,922 tumor cases and analyzed the matches of the codes for the
      position of tumors (C code) and the modality of tumors (M code). On the basis of
      searching result, mistakes in the coding were identified and the causes for these
      errors explored. RESULTS AND CONCLUSION: Altogether 5,329 mistakes occurred in
      relation to the arrangement of C code and M code for various and complicated
      reasons, accounting for 19.79% among the cohort of cases investigated. The
      present methodology for the coding needs to be improved and better alternatives
      are possible on the basis of current technology.

PMID- 14965824
TI  - Touch-down PCR and single-strand conformation polymorphism for detecting clonal T
      cell receptor gamma gene rearrangement in lymphoid leukemia.
AB  - OBJECTIVE: To explore the value of detecting clonal T cell receptor gamma (TCR
      gamma) gene rearrangement with touch-down PCR and single-strand conformational
      polymorphism analysis (SSCP) in the diagnosis of lymphoid leukemia. METHODS: The
      DNA of peripheral blood leucocytes from lymphoid leukemia patients were extracted
      for amplification of the TCR-gamma gene rearrangement with the consensus primers
      and touch-down PCR. The PCR products were analyzed by agarose gel
      electrophoresis, direct DNA sequencing and SSCP analysis. The positive control
      cell line DNA was mixed in different proportions with the DNA extracted from
      reactive lymphoid tissue to test the sensitivity of the touch-down PCR. RESULTS:
      Fifteen of 18 T lymphoid leukemia and 2 of the 4 B lymphoid leukemia patients
      were identified to be positive by agarose electrophoresis. The positive PCR
      products were further analyzed by SSCP analysis, which showed discrete bands.
      Direct DNA sequencing confirmed the clones to be TCR-gamma gene rearrangement,
      and the sensitivity of touch-down PCR was 1%. CONCLUSION: Consensus primers for
      studying TCR-gamma gene rearrangement in combination with touch-down PCR can
      effectively amplify the clonal TCR-gamma gene rearrangement in T lymphoid
      leukemia.

PMID- 14965825
TI  - In vitro culture and induced differentiation of adult rat neural stem cells from
      the corpus striatum.
AB  - OBJECTIVE: To investigate the in vitro multipotential differentiation of neural
      stem cells from adult rat corpus striatum. METHODS: The neural stem cells
      isolated from adult rat corpus striatum were cultured in serum-free medium to
      obtain cell suspension before monoclonal subculturing and differential induction.
      Immunocytochemical staining and reverse transcriptional PCR (RT-PCR) were
      performed to identify the properties of the differentiated cells. RESULTS:
      Numerous cell clusters were formed in the phase of monoclonal culture, and
      different types of cells were observed 3 d after induction with fetal bovine
      serum. The differentiated cells contained cells positive for nestin, neuron
      specific enolase (NSE) positive cells, and glial fibrillary acidic protein (GFAP)
      positive cells. RT-PCR identified expressions of the transcripts for neural cell
      associated genes including brain factor-1, gamma-aminobutyric acid alpha-receptor
      gamma-subunit, tyrosine hydroxylase and tryptophan hydroxylase. CONCLUSION: The
      cells separated from adult rat corpus striatum possess the ability of self
      proliferation and multipotential differentiation, and are identified as the stem
      cells of the central nervous system.

PMID- 14965826
TI  - Monitoring of T lymphocyte subset during ATG induction therapy in hand allograft
      with report of 3 cases.
AB  - OBJECTIVE: To investigate the significance of T lymphocyte subset determination
      during antithymocyte globulin (ATG) induction therapy in reducing the total drug
      dose, incidence of complications and cost of treatment in hand allograft.
      METHODS: The changes in peripheral blood T lymphocyte subsets (CD3+, CD4+, CD8+,
      and CD28) were determined by flow cytometry in 3 cases of hand allograft who
      received ATG treatment. RESULTS: Flow cytometry showed that the percentages of
      CD3+, CD4+, and CD8+ T lymphocytes, along with the ratio of CD4/CD8, decreased
      significantly during ATG induction therapy, and the results were consistent in
      the 3 cases. Long-term continuous changes of peripheral blood lymphocytes were
      observed after antithymocyte globulin induction therapy. CONCLUSION: The
      understanding of the immunological state of the patient with hand allograft after
      ATG induction therapy by monitoring T lymphocyte subsets may allow adjustment of
      the total dose of the drugs administered and help prevent the occurrence of
      complications.

PMID- 14965827
TI  - Multiple organ injury at early stage of intestinal and hepatic ischemia
      reperfusion in rats.
AB  - OBJECTIVE: To investigate the early-stage multiple organ injuries in rats
      subjected to intestinal and hepatic ischemia-reperfusion. METHODS: Seventy-five
      normal male Wistar rats were randomized equally into hepatic ischemia, intestinal
      ischemia and intestinal-hepatic ischemia groups. Before and at the end of
      occlusion (45 min), as well as at the time points of 0.5, 2.0 and 6.0 h during
      the reperfusion, respectively, 5 rats from each group were killed to obtain
      samples for determination of the contents of malondialdehyde (MDA), superoxide
      dismutase (SOD) in the blood, lung, kidney, pancreas and heart tissues, along
      with blood urea nitrogen (BUN), amylase (AMY), and creatine kinase MB (CK-MB).
      RESULTS: The activity of SOD was decreased (P<0.05) and MDA, BUN, AMY and CK-MB
      levels increased significantly (P<0.05) after ischemia-reperfusion as compared
      with those before ischemia. CONCLUSIONS: Intestinal and hepatic ischemia
      reperfusion can induce injury of multiple organs at early stage. With the same
      duration of ischemia-reperfusion, intestinal ischemia may induce severer injury
      than hepatic ischemia.

PMID- 14965828
TI  - Bacterial growth characteristics in craniocerebral gunshot wound of cat in a hot
      and humid environment.
AB  - OBJECTIVE: To investigate the growth behavior of characteristics in
      craniocerebral gunshot wound of cats in a hot and humid environment. METHODS:
      Twenty-three cross-bred cats were randomly divided into 4 groups: group A, the
      gunshot wound control group at normal temperature, in which tissue sampling was
      performed immediately after the wounding; group B, another gunshot wound control
      group at normal temperature, in which the samples were taken 6 h after the
      wounding; group C, the gunshot wound group subjected to a hot and humid
      environment, in which the tissue samples were obtained 6 h after the wounding;
      group D, the control group without undergoing the wound. The tissues from the
      wound tract and the surrounding tissues were sampled for bacterial culture and
      counting. RESULTS: The bacterial counts of the tissues from the wound tract, the
      tissues within 5 mm and within 5-10 mm from wound tract varied insignificantly
      between groups A, B and C (P>0.05). In each group, the bacterial counts declined
      in the tissues as the distance of the sampling sites from the wound tract
      increased (P<0.01). The bacterial counts of the tissues from the wound tract and
      within 5 mm from the wound tract in group A, B and C were significantly different
      from those in group D (P<0.01). CONCLUSION: Hot and humid environment does not
      significantly affect the bacterial growth in the craniocerebral gunshot wound
      within the first 6 h, which is a safe period against rapid bacterial growth and
      suitable for debridement.

PMID- 14965829
TI  - Clinical significance of detection of carotid artery plaque in patients with
      acute coronary syndrome.
AB  - OBJECTIVE: To study the intima-media thickness (IMT), plaque score in the carotid
      artery of patients with acute coronary syndrome (ACS) and the relationship
      between high-sensitivity C-reactive protein (hs-CRP) and the plaque score.
      METHODS: Using high-resolution ultrasonic instrument, IMT and the plaque score in
      the carotid artery were detected in 30 patients with ACS, 29 patients with stable
      angina pectoris  SAP   and 17 control subjects, in addition to the measurement of
      hs-CRP. RESULTS: Compared with SAP and control groups, IMT, total plaque score,
      soft and hard plaque scores in the carotid artery in ACS group were significantly
      increased (P<0.001). Hs-CRP (4.336+/-1.334 mg/L) in ACS group were significantly
      increased (P<0.001) as compared with that in SAP group (2.205+/-0.458 mg/L) and
      control group (1.625+/-0.434 mg/L). Hs-CRP had positive relationship with the
      IMT, whole plaque score, soft and hard plaque scores in the carotid artery,
      respectively. CONCLUSION: IMT, total plaque score, soft and hard plaque scores in
      the carotid artery in ACS group are significantly increased, and hs-CRP is
      positively related to IMT, total plaque score, soft and hard plaque scores in the
      carotid artery, respectively.

PMID- 14965830
TI  - Expression of nestin, an intermediate filament protein, in human fetal hepatic
      stem cells.
AB  - OBJECTIVE: To explore a new oval cell marker by examining the expression of
      nestin in human fetal hepatic stem cells in various stages during human fetal
      development. METHODS: Human fetal tissue samples of various developmental stages
      were obtained and fixed for preparation of paraffin sections. The expression of
      nestin, generally recognized as a specific marker for neural precursor cells, in
      fetal hepatic stem cells was detected using immunocytochemical staining (ABC
      method). RESULTS: Nestin-positive oval cells, characterized to be hepatic stem
      cells, were found in the limiting plate, which arranged tightly in monolayer to
      form ductules that encapsulated the early-stage portal area in a sheath-like
      fashion, and also partially encapsulated the primary portal area. With the
      development of the secondary portal areas, the nestin-positive oval cells
      gradually centered around the Hering canal. In addition, some nestin-positive
      mononuclear cells were found scattering in the hepatic cords and sinusoids,
      especially in the mesenchymal tissue of the portal areas. CONCLUSION: Nestin
      positive oval cells exist in human fetal liver and their origin and function
      await further investigation.

PMID- 14965831
TI  - Clinical application of transarterial embolization for massive hemorrhage in the
      nasopharyngeal and maxillofacial regions.
AB  - OBJECTIVE: To study the effect and safety of transarterial embolization (TAE) in
      the management of massive hemorrhage in the nasopharyngeal and maxillofacial
      regions. METHODS: Forty-two cases of massive hemorrhage in the nasopharyngeal and
      maxillofacial regions were treated by TAE. Gelfoam particles, polyvinyl acohol
      particles, and metallic coil were used to for embolism of the external carotid
      artery, maxillary artery, facial artery, occipital artery, sphenopalatine artery
      and ascending pharyngeal artery respectively according to the angiographic
      findings and the region of hemorrhage sites. RESULTS: TAE was successfully
      performed in all the cases, and no recurrence or serious complications were
      observed in the 3 to 12-month follow-up. CONCLUSION: TAE is safe and effective in
      the treatment of massive hemorrhage in the nasopharyngeal and maxillofacial
      regions.

PMID- 14965832
TI  - Therapeutic effect of three-dimensional conformal radiotherapy on locally
      advanced pancreatic carcinoma.
AB  - OBJECTIVE: To evaluate the effects of the two conformal radiotherapy modalities
      in the treatment of locally advanced pancreatic carcinoma. METHODS: From October,
      1998 to June, 2001, 67 patients with locally advanced pancreatic carcinoma
      received conformal radiotherapy (CRT). Vacuum cushions were applied to immobilize
      the patients before contrast CT scans, the treatment plans were simulated by
      three-dimensional treatment planning system. The patients were randomized into
      group A to receive a total dose of 45-54 Gy given in 8-12 fractions completed in
      18-27 d and group B with a total dose of 45-54 Gy in 15-18 fractions within 20-25
      d. RESULTS: The partial and complete pain relief rates of the two groups were
      95.9% and 81.6%, respectively, one month after the completion of the
      radiotherapy, with a median survival of 12.5 months. The response rates of the
      patients and the 2-year overall survival rates in group A were 81.8% and 51.6%,
      respectively, and were 35.3% and 12.1% in group B. The low-dose fractionated CRT
      was superior than accelerated CRT. CONCLUSION: For patients with unresectable
      pancreatic cancer receiving low-dose fractionated CRT, a high dose targeted at
      the tumor can be given in a fraction and the normal surrounding tissues are
      exposed to low-dose radiation, to achieve good therapeutic effect with minimized
      adverse effects on normal tissues in relation to the exposure.

PMID- 14965833
TI  - Perfusion homogeneity of hepatic parenchyma in magnetic resonance imaging during
      splenoportography.
AB  - OBJECTIVE: To evaluate the homogeneity of hepatic parenchyma enhancement in
      magnetic resonance imaging during splenoportography (MRSP) in the portal phase.
      METHODS: MRSP was performed in 16 patients suspected of space-occupying lesions
      in the livers. The signal intensity of non-lesion abnormal perfusion areas and
      that of peripheral parenchyma were measured in all the scanning phases including
      unenhanced phase, portographic phase, equilibrium phase, and delayed phase.
      RESULTS: Perfusion abnormalities were observed in 8 non-lesion foci in the portal
      phase in 4 cases of hepatic cirrhosis, most frequently appearing in triangle or
      fan-like shapes (7/8) with unpredictable locations. Hepatic cirrhosis patients
      had more non-lesion perfusion abnormalities than non-cirrhosis patients.
      CONCLUSIONS: The presence of non-lesion perfusion abnormalities in MRSP does not
      affect the diagnosis of the disease, and more homogeneous enhancement of the
      hepatic parenchyma in the portal phase can be achieved in MRSP than in CT during
      arterial portography and magnetic resonance imaging during arterial portography.

PMID- 14965834
TI  - Dynamics of intestinal flora after oral vaccination with inactivated whole
      cell/recombinant B subunit O139 cholera vaccine.
AB  - OBJECTIVE: To investigate the change of intestinal flora in subjects receiving
      oral vaccination with inactivated whole-cell/recombinant B subunit (WC/rBS) O139
      cholera vaccine made in China. METHODS: The fecal smears of 5 groups of subjects
      receiving the vaccine were collected before and 2 and 3 months after the
      vaccination to examine the distribution of the intestinal flora. RESULTS: In the
      458 specimens examined, the total amount of bacteria and percentages of G+b, G+c
      and G-c were decreased whereas the amount of G-b significantly increased after
      vaccination. Compared with the placebo control group, the vaccinated groups
      exhibited significant changes in G+b and G-c, which also varied significantly
      between the group receiving 3 doses of WC/rBS vaccine and the other vaccinated
      groups. The vaccination produced distinct changes in the percentage of the
      intestinal flora at different time points, showing the most obvious effect on G
      b. Oral vaccination was shown to affect the percentage of the intestinal flora
      very likely through its effect on the amount of G-b. The percentages of G+b, G-b
      and G-c varied significantly between male and female subjects after vaccination.
      CONCLUSION: Oral vaccination with WC/rBS affects the intestinal flora in human,
      and the mechanism as well as the implications needs to be further explored.

PMID- 14965835
TI  - Effects of lidocaine on cerebral oxygen supply-consumption balance and
      hemodynamics during anesthesia induction in patients with supratentorial tumor.
AB  - OBJECTIVE: To study the effects of lidocaine on the balance between cerebral
      oxygen supply-consumption and on the hemodynamics during anesthesia induction in
      patients with supratentorial tumor. METHODS: Twenty-four patients with
      supratentorial tumor were randomly divided into lidocaine group (n=12) and
      control group (n=12). Blood gas analysis and determinations of plasma lactic acid
      and glucose in the radial artery and internal jugular venous bulb were performed.
      Oxygen extraction ratio (OER) and blood oxygen content in the artery and internal
      jugular venous bulb were calculated during anesthesia induction. RESULTS: OER and
      difference declined in plasma lactic acid level between the internal jugular
      venous bulb and the artery, and blood oxygen saturation as well as blood oxygen
      pressure in the internal jugular venous bulb and the artery increased along with
      blood oxygen content in the internal jugular venous bulb in both groups during
      anesthesia induction. Comparison between the groups showed that only the changes
      in blood oxygen pressure in the internal jugular venous bulb were statistically
      significant. Changes in the hemodynamics in lidocaine group were less obvious
      than those in the control group during anesthesia induction. CONCLUSION:
      Lidocaine does not significantly influence cerebral oxygen balance and may
      effectively inhibit hemodynamic response during anesthesia induction in patients
      with supratentorial tumor.

PMID- 14965836
TI  - Effect of hypertension on the morphology of coronary artery: analysis of 203
      cases.
AB  - OBJECTIVE: To investigate the morphological features of the coronary artery
      visualized in angiography in hypertensive patients. METHODS: A total of 203
      patients (including 159 male and 44 female patients aged 29 to 75 years) with
      suspected coronary artery disease were studied during the period from November
      1999 to November 2001. All the patients received clinical examination and
      selective coronary angiography, and were divided into hypertensive and
      normotensive groups for comparison. RESULTS: There were 5.7+/-1.2 vascular curves
      in the hypertensive group, but only 3.1+/-0.8 in normotensive group, showing
      significant differences between the 2 groups (P<0.01). The bifurcation lesion was
      found in 34.5% patients in hypertensive group, but in only 23.1% in normotensive
      group (P<0.01). CONCLUSION: Hypertensive patients have more cardiovascular curves
      and bifurcation lesions in comparison with normotensive patients.

PMID- 14965837
TI  - Prognostic value of exercise in combination with 24-hour ambulatory blood
      pressure monitoring in elderly hypertensive patients.
AB  - OBJECTIVE: To investigate the prognostic value of exercise combined with 24-hour
      ambulatory blood pressure monitoring (ABPM) in the elderly hypertensive patients.
      METHODS: Forty-five patients over 60 years old were asked to perform submaximal
      exercise with controlled symptoms according to modified Bruce protocol to detect
      exercise-induced hypertension, followed by ABPM. RESULTS: The blood pressure of
      all the patients was within normal range, but the exercise induced the peak blood
      pressure reached 211.98+/-9.37 mmHg/101.50+/-12.86 mmHg. Fourteen patients with
      exercise-induced hypertension conformed to the diagnosis of hypertension
      according to ABPM, who had significantly higher measurements in ABPM than the
      normotensive patients (P<0.001). CONCLUSION Exercise test combined with ABPM may
      help identify hypertension in early stage in elderly patients.

PMID- 14965838
TI  - Treatment of the posterior urethral stricture: experience with 13 cases.
AB  - OBJECTIVE: To review our experience with the treatment of posterior urethral
      stricture. METHOD: A elaborated retrospective analysis of the treatment of 13
      cases of posterior urethral stricture was conducted with the typical cases.
      RESULT: Good therapeutic results were achieved in these cases after treatment
      with cryoablation, electrotome or open surgery. CONCLUSION: Proper initial
      treatment, adequate surgical approach, anti-infection measures and postoperative
      urethral dilatation are the key elements in successful treatment of posterior
      urethral stricture.

PMID- 14965839
TI  - Value of angiography in the diagnosis of patients with small kidney.
AB  - OBJECTIVE: To explore the diagnostic value of angiography in small kidney
      patients. METHODS: Angiographies were performed in 32 patients with small kidney
      of unknown etiology or with suspected renal arterial stenosis (RAS). RESULTS:
      Twelve cases of renal atrophy due to RAS were diagnosed by angiography, which
      demonstrated renal artery stenoses or occlusions. Angiography of 17 patients with
      nephrogenic renal atrophy displayed homogeneous shrinkage of the renal arteries
      except in the ostium. In 3 patients with renal hypoplasia, angiography showed
      narrowed renal arteries and tiny renal arterial branches. CONCLUSION: Renal
      artery angiography is of important values in the differential diagnosis between
      renal atrophy due to RAS, nephrogenic renal atrophy and non-renovascular renal
      atrophy, and renal hypoplasia.

PMID- 14965840
TI  - Effect of blood purification on plasma levels of intact parathyroid hormone in
      patients with chronic renal failure.
AB  - OBJECTIVE: To study the effects of hemoperfusion and/or hemodialysis on plasma
      levels of intact parathyroid hormone (iPTH) in patients with chronic renal
      failure (CRF). METHODS: A total of 40 uremic patients were randomly divided into
      two groups to receive hemoperfusion in combination with hemodialysis (HP+HD) or
      exclusive hemodialysis (HD), respectively. Plasma iPTH concentration was measured
      by means of radio immunoassay. RESULTS: After the blood purification procedures,
      the patients' plasma iPTH levels were reduced from 1,508.70+/-1,268.89 to
      1,049.04+/-992.91 microg/ml (P<0.001) in HD group and from 1,600.70+/-1,151.15 to
      745.47+/-785.02 microg/ml (P<0.001) in HP+HD group. CONCLUSION: Blood
      purification with hemoperfusion plus hemodialysis may decrease plasma iPTH levels
      more efficiently than hemodialysis performed alone.

PMID- 14965841
TI  - Laparoscopic vertical banded gastroplasty for morbid obesity.
AB  - OBJECTIVE: To evaluate the clinical application of laparoscopic vertical banded
      gastroplasty (LVBG) for morbid obesity. METHODS: Four patients undergoing LVBG
      were evaluated by comparison of the preoperative and postoperative morbidities
      and body weights. RESULTS: Laparoscopic surgery was successfully performed in all
      the 4 cases without laparotomy. The average operative time was 210 min without
      intraoperative or postoperative complications. In the 24-month follow-up, the
      body weight was reduced by over 50% of the excessive weight. CONCLUSION: LVBG is
      an effective and safe treatment for morbid obesity.

PMID- 14965842
TI  - Application of jejunum with vascular pedicle in reconstruction of the digestive
      tract.
AB  - OBJECTIVE: To reconstruct the digestive tract using the jejunum with vascular
      pedicle after esophagectomy or gastrectomy, and observe the therapeutic effects
      and the patients' quality of life after the operation. METHODS: This study
      included a total of 25 patients, 10 of whom received proximal subtotal
      gastrectomy followed by reconstruction of the digestive tract with P-shaped
      jejunum for anastomosis of the esophagus and the residual stomach, 15 had total
      gastrectomy and anastomosis of the P-shaped jejunum with the esophagus inferior
      to the arch of aorta, with another 2 having total gastrectomy and the anastomosis
      superior to the arch of aorta. The pH value of the esophagus was tested, barium
      meal and gastroscopy were carried out 3 months after the operations, and the
      patients' quality of life assessed. RESULTS: Anastomotic leakage or infections in
      the thoracic or abdominal cavity occurred in none of the patients. All the
      patients had no postoperative difficulty in eating cooked rice, and were free of
      reflux esophagitis and burning sensation in the chest. The pH value of the
      esophagus was 5.5-6.6. Eight patients survived for more than 5 years.
      CONCLUSIONS: The effects of digestive tract reconstruction using the jejunum with
      vascular pedicle after esophagectomy or gastrectomy are satisfactory, especially
      in patients with esophageal cancer in the lower section or cardia cancer. This
      operation gives rise to low rate of operative complications, and insures good
      quality of life of the patients.

PMID- 14965843
TI  - From the editor--the debate about posttraumatic stress disorder and some thoughts
      about 9/11.

PMID- 14965844
TI  - Anosognosia in individuals with schizophrenia: toward recovery of insight.
AB  - This paper addresses the growing evidence that lack of insight, or unawareness of
      illness in people with schizophrenia, may actually be a medically based condition
      known as anosognosia. Major explanatory models and related research findings are
      discussed. A case scenario is presented, as well as current perspectives
      regarding assessment of insight and alternative treatment approaches.
      Implications for further research, nursing education, and practice also are
      included. With better understanding of the characteristics and treatment of
      diminished insight in individuals with schizophrenia, nurses can better assist
      clients to recover helpful insight that enables them to take an active role in
      managing their symptoms and problems.

PMID- 14965845
TI  - Self-report of depressed mood and depression in women with type 2 diabetes.
AB  - The purpose of this cross-sectional analysis (N = 53) was to (a) describe the
      self-reported prevalence of depressed mood and depression in women with type 2
      diabetes; (b) to describe the antidepressive agents and dosages prescribed for
      depression treatment in women with type 2 diabetes; and (c) to examine
      differences in diabetes-related health outcomes (physiologic, psychosocial, and
      health functioning variables) with respect to depressed mood. Forty-four percent
      of women in this sample reported a depressed mood and 34% of the sample reported
      a history of depression. The majority of women with a history of depression were
      taking an antidepressive agent at the time of assessment (94%). Most women were
      treated with selective serotonin reuptake inhibitors (SSRIs). Women with
      depressed mood demonstrated poorer psychosocial adjustment and health functioning
      compared to women without a depressed mood; however, no differences in
      physiological outcomes were demonstrated. Only 18% of the participants were
      currently being treated with psychotherapy in conjunction with medication.
      Further research on this understudied population is indicated.

PMID- 14965846
TI  - Mental health reforms and their impact on consumer and carer participation: a
      perspective from Victoria, Australia.
AB  - Victoria, Australia has experienced significant changes in the structure and
      delivery of mental health services over the past three decades. As a result of
      these changes, there is now an expectation that consumers of services and their
      carers have increased opportunities to participate in the design and delivery of
      services. There currently exists a paucity of research that examines the degree
      to which this goal has been realized in practice. This article presents findings
      from a qualitative research study investigating the perceptions of consumers and
      carers regarding the degree to which the contemporary service system allows for
      their increased participation. Data were collected through in-depth interviews
      with consumers and carers. The findings suggest that consumers have identified an
      increased scope for their participation, although this varies considerably from
      service to service. Carers on the other hand described very little opportunity
      for participation at any level. The responses of carers suggest there may be some
      inherent difficulty in facilitating increased participation for both groups.
      Strategies to support carer participation are urgently required if the goals of
      state and national mental health policy in Australia are to be realized.

PMID- 14965847
TI  - Parental bonding: a key factor for mental health of college women.
AB  - The purpose of this study was to investigate the relationship of parental bonding
      to the mental health of college women aged 18 to 24 years. A cross-sectional
      study of a volunteer sample of 246 college women was conducted. Data on
      depressive symptoms, negative thinking, self-esteem, and parental bonding were
      collected via self-report. Maternal care was the strongest predictor of all four
      mental health indices. Paternal overprotection predicted scores of three of the
      four mental health measures. Women with optimal maternal and paternal bonding
      profiles (high care/low overprotection) had fewer depressive symptoms, less
      negative thinking, and higher self-esteem than women with other bonding profiles.
      The findings have implications for prevention, screening, and intervention to
      enhance the mental health of college women.

PMID- 14965848
TI  - Minority adolescent women with sexually transmitted diseases and a history of
      sexual or physical abuse.
AB  - Life history methods were used to obtain a more in-depth understanding of the
      configuration of psychosocial and situational factors that are associated with
      high-risk sexual behavior among minority adolescent women with a history of
      sexual or physical abuse and sexually transmitted disease (STD), to facilitate
      development of behavioral risk-reduction interventions. Study participants ranged
      in age from 14 to 18 years; 19 were Mexican American and 11 were African
      American. Women were recruited from clinics in a metropolitan health district.
      Various constitutive patterns unfolded during interview analysis including
      "fearing," "trusting," and "being a woman." The study revealed the perceptions of
      an extremely high-risk population of adolescent women regarding their STD risk,
      the context of their sexual relationships, sexual risk behaviors, contraception,
      and STD prevention, screening, and treatment practices. Intervention strategies
      based upon these findings are described.

PMID- 14965849
TI  - TIPS: telephone intervention--problem solving for persons with schizophrenia.
AB  - A prospective experimental design was used to examine whether face-to-face
      meetings designed to establish rapport had an effect on the verbal responses of
      persons with schizophrenia in subsequent Telephone Intervention--Problem Solving
      (TIPS). Verbal responsiveness was operationalized as length of telephone
      conversation, number of feeling statements expressed, and number of one-word
      responses. Experimental participants met with the TIPS provider twice during
      hospitalization, while controls did not meet with the TIPS provider. All subjects
      received TIPS weekly from a psychiatric nurse for six weeks after hospital
      discharge. Compared to controls, experimental participants conversed longer at
      every measurement point, and significantly longer during weeks one through three.
      Experimental participants were approximately twice as likely to make a feeling
      statement as those in the control group. These data suggest that psychiatric
      nurses who would like to employ TIPS to support clients in the community should
      plan for at least two face-to-face interventions to establish rapport prior to
      initiating TIPS.

PMID- 14965851
TI  - Genetics of suicide: an overview.
AB  - Risk for suicide may have heritable contributions. Evidence supporting this
      hypothesis includes strong and consistent findings from more than 20 controlled
      family studies indicating nearly 5-fold greater relative risk of suicidal acts
      among relatives of index cases with suicidal behavior compared to relatives of
      nonsuicidal controls. Relative risk was greater for completed suicide than for
      attempts. Contributions of genetic instead of environmental factors are indicated
      by a higher average concordance for suicidal behavior among co-twins of suicidal
      identical twins compared to fraternal twins or to relatives of other suicidal
      subjects, in at least seven studies. Three studies indicate significantly greater
      suicidal risk, particularly for completed suicide, among biological versus
      adoptive relatives of suicidal or mentally ill persons adopted early in life.
      Molecular genetics studies have searched inconclusively for associations of
      suicidal behavior with genes mainly for proteins required for central
      serotonergic neurotransmission. Complex interactions of environmental with
      heritable risk and protective factors for suicide and psychiatric illnesses or
      vulnerability traits are suspected, but specific intervening mechanisms remain
      elusive. Familial or genetic risks for psychiatric factors strongly associated
      with suicide, such as major affective illnesses and alcohol abuse, as well as
      impulsive or aggressive traits, have not consistently been separated from
      suicidal risk itself.

PMID- 14965852
TI  - Antisuicide properties of psychotropic drugs: a critical review.
AB  - The authors consider the extent to which psychotropic medications demonstrate
      benefits in the prevention of suicidal behavior in psychiatric patients. Results
      of a MedLine search are critically reviewed for lithium, divalproex and other
      anticonvulsants, conventional and atypical antipsychotics, and antidepressants.
      The existing literature is almost entirely limited to noncontrolled, often
      retrospective studies that do not control for potential biases in treatment
      selection, the use of multiple medications, the impact of medication
      nonadherence, and nonrandomized treatment discontinuations. Nevertheless, an
      extensive literature has arisen regarding observed reductions in suicidal
      behavior with lithium for mood disorders and, to a lesser extent, with clozapine
      for schizophrenia. A substantially smaller literature suggests more negative than
      positive data with divalproex or carbamazepine in bipolar disorder, while minimal
      information exists regarding suicidality with atypical antipsychotics other than
      clozapine. Studies of antidepressants have mostly been short-term and have
      focused more on whether they induce (rather than ameliorate) suicidal thoughts or
      behaviors. The sum of existing studies is generally inconclusive about whether
      antidepressants appreciably reduce risk for suicide completions. Relatively
      little is known about pharmacotherapy effects on suicidal ideation as distinct
      from behaviors. Possible mechanistic considerations for understanding antisuicide
      properties include a therapeutic impact on depression, impulsivity, or
      aggression, potentially mediated through serotonergic or other neuromodulatory
      systems. Recommendations are provided to guide future research as well as
      clinical practice.

PMID- 14965853
TI  - Half in love with easeful death: the meaning of chronic suicidality in borderline
      personality disorder.
AB  - Chronic suicidality is a central feature of borderline personality disorder.
      While suicidal thoughts and attempts are highly prevalent in borderline patients,
      completion is relatively unpredictable. Self-cutting seems to function as a means
      of affective regulation. In borderline personality disorder, suicidality performs
      a set of psychological functions and can sometimes become "a way of life."
      Strategies developed for acutely suicidal patients may not be effective in
      chronic suicidality. Since there is no evidence that hospitalization prevents
      completion, an ambulatory approach to the management of chronically suicidal
      patients may be most useful.

PMID- 14965854
TI  - The impact of a patient's suicide on psychiatric trainees: a case study and
      review of the literature.

PMID- 14965855
TI  - The best kept secret: how to form an effective alliance.

PMID- 14965856
TI  - The profiling of ego defenses in clinical material to assess recovery from
      schizoaffective disorder.

PMID- 14965857
TI  - Wavelet based analysis and characterization of the ECG signal.
AB  - This paper reports the use of a wavelet analysis technique based on the Mexican
      Hat wavelet to identify the onset and termination points and the duration of the
      principal constituent components of the human electrocardiogram (ECG). ECG
      recordings were obtained from 21 healthy subjects aged between 13 and 65 years,
      over a wide range of heart rates extending from 46 to 184 beats min(-1). A
      wavelet transform method was then used to locate precisely the positions of the
      onset, termination and the durations of individual components in the ECG.
      Component times were then classified according to the heart rate associated with
      the cardiac cycle to which the component belonged. Second order equations of the
      form [formula in text] were fitted to the data obtained for each component to
      characterize its timing variation.

PMID- 14965858
TI  - Analysis of the ST-segment in terms of principal components: application on
      multichannel magnetocardiographic recordings.
AB  - Parameterization of the ST-segment is used as a tool for risk stratification for
      patients to suffer from ventricular tachycardia. This parameterization is
      performed in terms of Principal Component Analysis (PCA) applied on multichannel
      magnetocardiographic (MCG) recordings. 55-channel MCG was recorded from 14 normal
      persons, 10 patients with CHD, 14 patients with MI, and six patients with VT. We
      found a significantly (p < 0.05) lower PCA-score in patients with MI compared to
      normals. The lowest PCA-score was found in VT patients. Significant differences
      can be found between VT patients and normals and also between VT patients and CHD
      patients.

PMID- 14965859
TI  - On lossy transform compression of ECG signals with reference to deformation of
      their parameter values.
AB  - Electrocardiogram (ECG) signals are the most prominent biomedical signal type
      used in clinical medicine. Their compression is important and widely researched
      in the medical informatics community. In the previous literature compression
      efficacy has been investigated only in the context of how much known or developed
      methods reduced the storage required by compressed forms of original ECG signals.
      Sometimes statistical signal evaluations based on, for example, root mean square
      error were studied. In previous research we developed a refined method for signal
      compression and tested it jointly with several known techniques for other
      biomedical signals. Our method of so-called successive approximation quantization
      used with wavelets was one of the most successful in those tests. In this paper,
      we studied to what extent these lossy compression methods altered values of
      medical parameters (medical information) computed from signals. Since the methods
      are lossy, some information is lost due to the compression when a high enough
      compression ratio is reached. We found that ECG signals sampled at 400 Hz could
      be compressed to one fourth of their original storage space, but the values of
      their medical parameters changed less than 5% due to compression, which indicates
      reliable results.

PMID- 14965860
TI  - A simple device to assess and train motor coordination.
AB  - PURPOSE: The purpose of this project was to develop a computer program which can
      be used on a laptop or other IBM-based computer to assess and train motor
      coordination in children with closed head trauma or cerebral palsy. APPARATUS:
      Muscle coordination was assessed by the child's ability to track a series of
      lines of increasing complexity. A stylus was used by the child to trace lines on
      a computer screen. Two different line tests were used. In the first, lines of
      various complexities were drawn on the screen at various angles. The child was
      asked to trace the line and the accuracy with which the line was traced was
      determined, providing a score. In a second test, a line was drawn on the screen
      and the child was asked to trace the line as it was drawn. The error in tracking
      the line and the time to track the line both were used to evaluate and score the
      child's performance. Finally, a 'Winnie the Pooh' character was flashed on the
      screen with distracters such as trees and other animals, and the child was asked
      to touch the Pooh. By increasing the speed of movement and decreasing the
      duration that the characters appeared on the screen, the child could be
      challenged. Successful touching of a character resulted in a positive score.
      EXPERIMENTAL TESTING: Six children with cerebral palsy were compared to five
      children who did not have cerebral palsy, to evaluate the device. While both
      groups of children showed an increase in motor skills using the program, the
      increase seen in the children with cerebral palsy was 5-fold greater than that of
      the control group. CONCLUSIONS: While only a few children were tested with the
      device, the device seems to prove quite useful for physical and occupational
      therapy for working on motor skills in children. More investigation is warranted.

PMID- 14965861
TI  - Standing-up robot: an assistive rehabilitative device for training and
      assessment.
AB  - In this paper a robotic assistive device is presented, aimed at assisting
      physically impaired individuals when rising from a sitting to a standing
      position. The robotic device is designed as a three degrees of freedom (3-DOF)
      mechanism supporting the subject under the buttocks. The device is driven by an
      electrohydraulic servosystem capable of operating in multiple control modes. It
      is instrumented with a sensory system providing information about the standing-up
      parameters. Evaluation of the standing up assistive device was accomplished in
      robot-supported rising trials of a paraplegic subject. The experiments
      demonstrated that stable risings in different standing - up manoeuvres were
      achieved. The measurement results revealed the role of the arm support and the
      support of the artificially evoked moments in the paralysed lower extremities
      during rising. The results show that the device can be used efficiently for
      training and evaluation of standing up manoeuvres.

PMID- 14965862
TI  - A device to measure in vivo forces in human flexor tendons during carpal tunnel
      operations.
AB  - An apparatus has been designed to measure the in vivo forces transmitted along
      human hand flexor tendons during carpal tunnel release procedures. The tendon
      will be run through three hooks, the central one of which is attached to a load
      cell. The rationale is that once these forces are known this will aid in the
      design of repair techniques and rehabilitation regimens. As a first stage, an in
      vitro validation study is presented using cord subjected to varying forces to
      mimic an in vivo flexor tendon under varying conditions of use. Our results show
      that we can accurately and reproducibly measure the force in the cord.

PMID- 14965863
TI  - Management of anticoagulant therapy for patients with prosthetic heart valves or
      atrial fibrillation.
AB  - There is a wide array of recommendations for the management of anticoagulant
      therapy in patients with mechanical heart valves. Especially the optimal
      intensity of vitamin K antagonists (VKA) is a ongoing matter of debate. On the
      basis of several studies, recommendations for daily clinical practice can be
      made. In this review, we discussed the studies and the different guidelines.
      Guidelines for the prevention of thromboembolic complications in patients with
      atrial fibrillation are more stringent. VKA with a target INR between 2.0 and 3.0
      is more effective in the prevention of stroke than aspirin, especially in the
      presence of riskfactors for thromboembolism (age above 65, previous
      thromboembolism, history of hypertension and diabetes, enlarged left atrial
      diameter and left ventricular dysfunction). In the absence of clinical or
      echocardiographical riskfactors for thromboembolism, patients may be safely
      treated with aspirin.

PMID- 14965864
TI  - The use of fluorescence in situ hybridization (FISH) in chronic lymphocytic
      leukemia (CLL).
AB  - As a result of the low proliferative index, only 50% of chronic lymphocytic
      leukemia cases are adequate for cytogenetic analysis. Of these, about half have
      clonal abnormalities. The application of fluorescence in situ hybridization
      (FISH) to CLL has substantially enhanced our ability to detect chromosomal
      aberrations; the incidence of a number of recurring abnormalities has been
      established, providing new insights into the pathogenesis of this disease with a
      direct impact on the prognosis.

PMID- 14965865
TI  - Molecular monitoring of minimal residual disease in patients with multiple
      myeloma.
AB  - Improvement of transplantation strategies and a multitude of emerging novel
      therapies result in a better treatment outcome in patients with multiple myeloma
      (MM). This gives rise to the need for sensitive methods to detect minimal
      residual disease (MRD) in MM. Qualitative molecular monitoring using allele
      specific oligonucleotide PCR for the immunoglobulin heavy chain (IgH) is well
      established to detect clonotypic cells after therapy or in stem cell harvests.
      Recently, real-time IgH PCR or limiting dilution based PCR assays offer the
      possibility to quantify the amount of residual tumour cells. In this review,
      different qualitative and quantitative IgH PCR techniques will be discussed as
      well as the current clinical role of molecular monitoring of MRD in patients with
      MM.

PMID- 14965866
TI  - Thalidomide effects in the post-transplantation setting in patients with multiple
      myeloma.
AB  - Thalidomide recently has been proven to have an impact on plasma cell dyscrasia
      through multiple mechanisms. Its effects on hematopoietic stem cells both in
      harvesting and in the immediate post-transplant setting are still unknown. We
      report on 12 cases (9 males and 3 females), median age 56 years old (range 41-65
      years old) who underwent autologous peripheral stem cell transplantation for
      multiple myeloma and received thalidomide as maintenance therapy post
      transplantation. Patients received various cytoreductive therapies prior to stem
      cell harvest. Eleven patients were in partial remission (PR) and one in complete
      remission (CR) on entry into the transplant phase of therapy. The median CD34+/kg
      harvested was 4.7 x 10(6) (range 1.9-55.4 x 10(6) CD34+/kg). All patients
      received intravenous melphalan 200 mg/m2 as their conditioning regimen. Six of
      twelve patients attained a CR post-transplant, and six a PR. Thalidomide was
      started after all patients engrafted post-transplant (absolute neutrophil count
      >0.5 x 10(9)/l and self-sustained platelet count >20 x 10(9)/l) and following
      satisfactory resolution of transplant toxicity including mucositis and diarrhea.
      Thalidomide was initiated at a median of 43 days post-transplant (range 23-138
      days). The median leukocyte and platelet counts at the moment of thalidomide
      initiation were 5.8 x 10(9)/l (range 2.9-8.6 x 10(9)/l) and 196 x 10(9)/l (range
      30-351 x 10(9)/l), respectively. Thalidomide was started at 100 mg daily,
      increasing 100 mg/day/month until reaching a dose of 400 mg/day. One patient
      failed to tolerate thalidomide due to CNS symptoms and stopped therapy at 12
      days. Another patient stopped thalidomide therapy after 71 days, because of
      severe fatigue secondary to hypothyroidism. The most common adverse effects were
      constipation (5), rash (4), dry skin (3) and dizziness (3). No grade 3-4 adverse
      effects were documented. Neutropenia, previously reported as an adverse effect in
      this setting, was not seen to date in our cohort. All patients attained a CR or
      PR after transplant and thalidomide maintenance. We have had two relapses during
      a median follow-up of 68 weeks (range 42-172 weeks). CONCLUSION: Thalidomide
      appears to be a safe drug in the post-transplant setting, perhaps adding to the
      response achieved post-transplant without major toxicity. Longer follow up and
      future randomized trials will be needed to validate the role of thalidomide and
      its long-term effect when used as maintenance therapy in the post-transplant
      setting.

PMID- 14965867
TI  - Th1/Th2 cells in patients with multiple myeloma.
AB  - Multiple myeloma (MM) is a lymphoproliferative disorder that is characterized by
      a proliferation of clonal B cells in various stages of maturation that then
      infiltrate the bone marrow. MM has been reported to accompany various T cell
      abnormalities including quantitative and functional defects of CD4+ and CD8+ T
      cells. Recently, immunotherapy such as dendritic cell therapy, vaccination
      therapy, and anti-tumor antibody therapy, has been attempted in patients with MM.
      To develop more effective immunotherapy for patients with MM, further studies are
      required to identify the immunological abnormalities, especially in T cells,
      associated with MM. The T helper 1 (Th1) and T helper 2 (Th2) cells are
      characterized by distinct cytokine production patterns. The Th1 cells produce
      interferon gamma and interleukin-2 (IL-2), and are involved in cell-mediated
      immunity. The Th2 cells produce IL-4 and promote humoral immunity by stimulating
      antibody production, particularly IgE responses. Furthermore, Th1 and Th2 cells
      have been found to cross-regulate each other's development. The Th1/Th2
      combination has an important role in immune response to many disorders including
      infection, autoimmune diseases, and malignancies. In this review, we report a
      Th1/Th2 imbalance in cases of MM, and discuss the relationship between T cell
      abnormalities and the pathology of MM.

PMID- 14965868
TI  - Reversal of MDR by verapamil analogues.

PMID- 14965869
TI  - Clinico-haematological profile of HbE syndrome in adults and children.
AB  - Haemoglobin E beta thalassemia (HbE beta thalassemia) has a remarkable
      variability in clinical expression ranging from a mild form of thalassemia
      intermedia to a transfusion dependent condition. An overlap between the mild
      variety of HbE beta thalassemia and homozygous HbE disease is common, however,
      differentiation is required for early institution of therapy and for predicting
      the later clinical course. Fifty cases of Hb E syndrome comprising of 43 cases of
      Hb E beta thalassemia and 7 cases of homozygous HbE disease were studied. Their
      clinico- haematological features and results of high performance liquid
      chromatography (HPLC) were analysed.

PMID- 14965870
TI  - Plasma levels of TNF-alpha in sickle cell patients receiving hydroxyurea.
AB  - Hydroxyurea (HU), a chemotherapeutic agent, used increasingly in the treatment of
      sickle cell disease (SCD) stimulates the release of a tumor necrosis factor (TNF
      alpha) from human macrophages in vitro and the concentration of TNF-alpha is
      greater than normal in subjects affected by SCD. It is widely accepted that HU
      may inhibit vaso-occlusive crisis (VOC) by stimulating the production of fetal
      hemoglobin (HbF) and nitric oxide (NO) in SCD; however, the beneficial effects of
      HU in vivo may be counteracted by the release of TNF-alpha and, in turn, the
      expression of a vascular cell adhesion molecule (VCAM-1) on leukocytes. Previous
      studies have shown that the severity of SCD increases with the leukocyte count.
      Therefore, we examined the relationship between plasma levels of TNF-alpha and
      HbF in SCD patients during steady-state (StSt) conditions (in the absence of VOC)
      and during VOC conditions after the acute administration of HU. Venous blood was
      collected in SCD patients over 6 h after administering a single dose of HU.
      Plasma TNF-alpha was found to be greater in SCD subjects than in reported normal
      adult controls (p<0.05). TNF-alpha in the StSt group was not significantly
      different than in the VOC group; however, the plasma TNF-alpha tended to greater
      in the VOC group (p>0.1). An increase in the HbF concentration after acute
      administration of HU (p<0.01) was not associated with a significant change in
      plasma TNF-alpha (p>0.1). Contrary to the results of in vitro studies, HU did not
      increase the plasma concentration of TNF-alpha. These findings suggest that a HU
      induced increase in TNF-alpha does not contribute to VOC and sickle cell patients
      can be counseled that the HU-induced increase in TNF-alpha does not counteract
      the beneficial effects of HU in SCD.

PMID- 14965871
TI  - Clinical and laboratory study of an episode of cefotetan-induced severe hemolytic
      anemia.
AB  - BACKGROUND: Cephalosporins are frequently associated with positive direct
      antiglobulin tests (DAT) and may rarely cause immune hemolytic anemia (IHA). We
      describe a patient who developed hemolytic anemia while she was receiving
      intravenous cefotetan. STUDY DESIGN AND METHODS: Immunohematologic studies of
      drug-dependent antibodies were performed by using cefotetan-treated red blood
      cells (RBCs) and untreated RBCs in the presence of cefotetan. RESULTS: The
      patient's serum contained antibodies that reacted with both drug-coated RBCs
      (adsorption mechanism) and with uncoated RBCs when cefotetan was added to the
      serum (immune complex mechanism). The prompt recognition of the problem and
      discontinuation of the drug prevented the onset of renal failure and rapidly
      resolved the hemolytic reaction. CONCLUSION: Our report underlines the importance
      of close laboratory and immunohematologic monitoring of patients treated with
      cephalosporins in order to recognize swiftly any hemolytic reaction due to these
      antibiotics thus reducing the chance of serious sequelae.

PMID- 14965872
TI  - Enhanced neutrophil apoptosis in neutropenic patients with hepatosplenic
      schistosomiasis: evidence of serum Fas ligand.
AB  - Enhanced neutrophil apoptosis has been reported in neutropenic hepatosplenic
      schistosomiasis. The shortening of neutrophil survival via apoptosis may explain
      the neutropenia that occur in these patients. However, the regulation of
      neutrophil apoptosis in hepatosplenic schistosomiasis has not been clearly
      defined. Neutrophils harvested from neutropenic patients with hepatosplenic (HS)
      schistosomiasis, (n=25), non-neutropenic patients with hepatointestinal (HI)
      schistosomiasis (n=10), and age-/gender-matched healthy control subjects (n=10)
      were incubated with autologous serum. Neutrophils apoptosis was quantified by
      flow cytometry through determination of propidium iodide nuclear staining and
      confirmed by DNA gel electrophoresis at 0 (i.e. fresh neutrophils), 4 and 24 h
      culture. Neutrophils from healthy subjects were also incubated with either 10%
      heterologous normal or neutropenic serum, with and without anti-Fas ligand
      antibody. Fas expression was assessed in fresh neutrophils using flow cytometry.
      Compared with normal healthy neutrophils, and HI neutrophils, neutropenic
      neutrophils demonstrated greater apoptosis in the presence of autologous serum
      (P<0.01, 0.05, respectively). Furthermore, compared with normal neutrophils
      exposed to heterologous normal serum, those exposed to heterologous neutropenic
      serum exhibited higher apoptosis rates ( P<0.01). Moreover, anti-Fas L antibody
      attenuated the neutropenic serum-induced neutrophil apoptosis in normal
      neutrophils. Fas expression was significantly higher in the neutropenic group
      when compared to both HI and normal healthy controls (P<0.05). In addition, Fas
      expression by neutrophils was paralleled by high neutrophil apoptosis. On the
      other hand, neutrophil apoptosis was not correlated to the size of spleen in
      neutropenic group. In conclusion, the rate of neutrophil apoptosis is accelerated
      in patients with neutropenic hepatosplenic schistosomiasisis. These findings
      suggest that the enhanced neutrophil apoptosis that occurs in neutropenic HS
      patients is triggered by a serum factor, which is mostly a Fas ligand.

PMID- 14965873
TI  - A 5-year-old boy with hepatosplenomegaly.

PMID- 14965874
TI  - Finite element analysis of the human ACL subjected to passive anterior tibial
      loads.
AB  - In this study, a constitutive law based on a nearly incompressible transversely
      isotropic hyperelastic potential is proposed to describe the mechanical behaviour
      of the anterior cruciate ligament (ACL). The constitutive formulation is valid
      for arbitrary kinematics (finite elasticity) and is thermodynamically admissible.
      Based on anatomic measurements performed on a human cadaveric knee specimen, a
      three-dimensional continuum finite element model of the ACL was developed. The
      numerical model was used to simulate clinical procedures such as the Lachman and
      drawer tests, which are performed to assess the existence and severity of an ACL
      injury. Finite element analyses showed that the two procedures have distinct
      effects on the behaviour of the ACL and provided new insights into the stress
      distributions. Moreover, good qualitative and quantitative agreement was found
      between the present study and results obtained experimentally in comparable
      conditions.

PMID- 14965875
TI  - A finite element beam-model for efficient simulation of large-scale porous
      structures.
AB  - This paper presents a new method for the generation of a beam finite element (FE)
      model from a three-dimensional (3D) data set acquired by micro-computed
      tomography (micro-CT). This method differs from classical modeling of trabecular
      bone because it models a specific sample only and differs from conventional solid
      hexahedron element-based FE approaches in its computational efficiency. The
      stress-strain curve, characterizing global mechanical properties of a porous
      structure, could be well predicted (R(2)=0.92). Furthermore, validation of the
      method was achieved by comparing local displacements of element nodes with the
      displacements directly measured by time-lapsed imaging methods of failure, and
      these measures were in good agreement. The presented model is a first step in
      modeling specific samples for efficient strength analysis by FE modeling. We
      believe that with upcoming high-resolution in-vivo imaging methods, this approach
      could lead to a novel and accurate tool in the risk assessment for osteoporotic
      fractures.

PMID- 14965876
TI  - Influence of aspect ratios on the creep behaviour of articular cartilage in
      indentation.
AB  - Indentation tests are commonly used to determine the mechanical behaviour of
      articular cartilage with varying properties, thickness, and geometry. This
      investigation evaluated the effect of changing geometric parameters on the
      properties determined from creep indentation tests. Finite element analyses
      simulated the indentation behaviour of two models, an excised cylindrical
      specimen of cartilage with either normal and repair qualities and an
      osteochondral defect represented as a cylindrical region of repair cartilage
      integrated with a surrounding layer of normal tissue. For each model, the ratios
      of indenter radius to cartilage height (a/h=0.5,1.5) and cartilage radius to
      indenter radius (r/a=2,5) were varied. The vertical displacement of the cartilage
      under the indenter obtained through finite element analysis was fitted to a
      numerical algorithm to determine the aggregate modulus, permeability, and
      Poisson's ratio. Indentation behaviours of cartilage specimens for either model
      with a/h=1.5 were not affected by r/a for values of 2 and 5. Aggregate modulus
      was not greatly affected by the geometric changes studied. Permeability was
      affected by changes in the ratio of specimen to indenter radii for a/h=0.5. These
      findings suggest that experimental configurations of excised cylindrical
      specimens, also representing osteochondral defects with no or unknown degree of
      integration, where the cartilage layer has a/h=0.5 should not have r/a values on
      the order of 2 for confidence in the mechanical properties determined.
      Indentation of osteochondral defects where the repair cartilage is fully
      integrated to the surrounding cartilage can be performed with confidence for all
      cases tested.

PMID- 14965877
TI  - Osteocyte-based image analysis for quantitation of histologically apparent
      femoral head osteonecrosis: application to an emu model.
AB  - Femoral head osteonecrosis is often characterized histologically by the presence
      of empty lacunae in the affected bony regions. The shape, size and location of a
      necrotic lesion influences prognosis, and can, in principle, be quantified by
      mapping the distribution of empty lacunae within a femoral head. An algorithm is
      here described that automatically identifies the locations of osteocyte-filled
      vs. empty lacunae. The algorithm is applied to necrotic lesions surgically
      induced in the emu, a large bipedal animal model in which osteonecrosis
      progresses to collapse, as occurs in humans. The animals' femoral heads were
      harvested at sacrifice, and hematoxylin and eosin-stained histological
      preparations of the coronal midsections were digitized and image-analyzed. The
      algorithm's performance in detecting empty lacunae was validated by comparing its
      results to corresponding assessments by six trained histologists. The percentage
      of osteocyte-filled lacunae identified by the algorithm vs. by the human readers
      was statistically indistinguishable.

PMID- 14965878
TI  - Modelling the behaviour of ligaments: a technical note.
AB  - Experimental observations suggest that during a ligament tensile strain test,
      water and glycosaminoglycans are exuded. Many attempts have been tried to model
      this behaviour using continuum mechanics. We have investigated this unique
      behaviour and have established three mechanisms which may contribute to the
      experimental observations: the slackness of the fibres before stretching can lead
      to a decrease in volume upon straightening; a Poisson's ratio higher than 0.5
      from the axial to the lateral direction (as recorded in the literature [Hewitt,
      J., Guilak, F., Glisson, R. and Parker Vail, T. (2001) "Regional material
      properties of the human hip joint capsule ligaments", Journal of Orthopaedic
      Research 19(3), 359-364]) due to the very high level of anisotropy of the tissue;
      and an osmotic pressure, with a certain level of anisotropy, that causes the
      swelling of the tissue before loading [Thornton, G.M., Shrive, N.G. and Frank,
      C.B. (2001) "Altering ligament water content affects ligament pre-stress and
      creep behaviour", Journal of Orthopaedic Research 19(5), 845-851]. There may be
      other mechanisms that also contribute in the observed fluid exudation on tensile
      loading.

PMID- 14965879
TI  - Genetically-designed neural networks for error reduction in an optimized
      biomechanical model of the human elbow joint complex.
AB  - A real time dynamic biomechanical model of the human elbow joint has been used as
      the first step in the process of calculating time varying joint position from the
      electromyograms (EMGs) of eight muscles crossing the joint. Since calculation of
      position has a high sensitivity to errors in the model torque calculation, a
      genetic algorithm (GA) neural network (NN) has been developed for automatic error
      reduction in the dynamic model. Genetic algorithms are used to design many neural
      network structures during a preliminary trial effort, and then each network's
      performance is ranked to choose a trained network that represents the most
      accurate result. Experimental results from three subjects have shown model error
      reduction in 84.2% of the data sets from a subject on which the model had been
      trained, and 52.6% of the data sets from the subjects on which the model had not
      been trained. Furthermore, the GA networks reduced the error standard deviation
      across all subjects, showing that progress in error reduction was made evenly
      across all data sets.

PMID- 14965880
TI  - Shape optimization of a cementless hip stem for a minimum of interface stress and
      displacement.
AB  - The primary stem stability is an essential factor for success of cementless hip
      stems. A correct choice of the stem geometry can improve the stem stability and,
      consequently, increase the life time of a hip implant. In this work, it is
      proposed a computational model for shape optimization of cementless hip stems.
      The optimization problem is formulated by the minimization of relative
      displacement and stress on bone/stem interface using a multi-criteria objective
      function. Also multiple loads are considered to incorporate several daily life
      activities. Design variables are parameters that characterize the geometry of
      selected cross sections, which are subject to geometric constraints to ensure a
      clinically admissible shape. The stem/bone set is considered a structure in
      equilibrium with contact conditions on interface. The contact formulation allows
      us to analyze different lengths of porous coating. The optimization problem is
      solved numerically by a steepest descent method. The interface stress and
      relative displacement are obtained solving the contact problem by the finite
      element method. Numerical examples are presented for a two-dimensional model of a
      hip stem, however, the formulation is general and can be applied to the three
      dimensional case. The model gives indications about the relation between shape,
      porous coating and prosthesis stability.

PMID- 14965881
TI  - Putting prevention back on the agenda.

PMID- 14965882
TI  - An evidence-based approach to planning tobacco interventions for Aboriginal
      people.
AB  - Systematic reviews have shown that interventions such as the delivery of
      cessation advice by heath professionals and the use of nicotine replacement
      therapy are effective at increasing cessation rates, however little is known
      about whether such interventions are appropriate and effective for and thus
      transferable to Aboriginal Australians. The aim of this paper was to assess
      whether evidence of effectiveness for brief interventions for cessation and
      nicotine patches from studies conducted in other populations was likely to be
      transferable to Aboriginal people in the NT. This paper involved assessment of
      systematic reviews of evidence for the use of brief interventions for smoking
      cessation and the use of nicotine replacement therapy, when planning two such
      interventions for delivery to Aboriginal people. Emerging themes are discussed.
      There were many factors which were likely to mean that these brief advice on
      cessation and the use of nicotine patches were likely to be less effective when
      implemented in Aboriginal communities. The planned interventions were delivered
      in primary care, and were of low intensity. Few studies included in systematic
      reviews were set in the developing world or in minority populations. Many
      features of the context for delivery, such as the normality of the use of tobacco
      among Aboriginal people, the low socio-economic status of this population and
      cultural issues, may have meant that these interventions were likely to be less
      effective when delivered in this setting. Further research is required to assess
      effectiveness of tobacco interventions in this population, as evidence from
      systematic reviews in other populations may not be directly transferable to
      Aboriginal people.

PMID- 14965883
TI  - Brief interventions: good in theory but weak in practice.
AB  - A substantial body of research evidence has accumulated in support of the
      efficacy of brief interventions for a number of alcohol and drug-related problem
      areas, most notably alcohol and tobacco. This evidence has been used to exhort a
      range of professional groups such as general practitioners (GPs), and more
      recently emergency department hospital staff to engage in brief interventions.
      Internationally, however, these secondary prevention efforts have largely failed.
      Why have these proven interventions not been embraced by frontline workers? This
      is a little-asked question as efforts to press-gang unwilling professionals to
      take up the cudgel continue. This paper examines the characteristics of brief
      interventions and their principal delivery agents and explores reasons for the
      failure to move from efficacy to effectiveness. Given the prevention potential
      that rests with brief intervention, these are crucial questions to address. A key
      feature of brief intervention delivery also examined is the role of GPs versus
      the less well-explored option of the practice nurse. It will be proposed that
      perhaps we have the right vehicle but the wrong driver and that until closer
      scrutiny is made of this issue efforts in this key prevention area will continue
      to fail to achieve optimum results.

PMID- 14965884
TI  - Making licensed venues safer for patrons: what environmental factors should be
      the focus of interventions?
AB  - The Queensland Safety Action Projects operationalized a problem-focused
      responsive regulatory model in order to make nightclubs and other venues safer. A
      problem-focused approach requires a careful analysis of the total environment of
      licensed venues, including drinking and its controls but also the social and
      physical environments, patron mix and management practices. We present new
      analyses of observational data collected in 1994 and 1996 in the north Queensland
      cities of Cairns, Townsville and Mackay. Major reductions in aggression and
      violence were observed, as well as improvements in many aspects of the venue
      environment and management practices. We do not argue in this paper that the
      interventions caused the environmental and management changes, although we
      believe this to be true. Rather, our assumption is that whatever caused them,
      some of the environmental and management changes were critical to the reductions
      in aggression. Regression techniques were used to identify those factors that
      best explained the declines in aggression. For reduced physical violence four key
      predictors were identified: improved comfort, availability of public transport,
      less overt sexual activity and fewer highly drunk men. For reduced non-physical
      aggression, four key predictors were: fewer Pacific Islander patrons, less male
      swearing, fewer intoxicated patrons requiring that management be called and more
      chairs with armrests. The analyses are consistent with the argument that the
      control of drinking is necessary but not sufficient to reduce aggression and
      violence.

PMID- 14965885
TI  - The effect of the Safer Bars programme on physical aggression in bars: results of
      a randomized controlled trial.
AB  - The purpose of this study was to evaluate the effectiveness of Safer Bars, an
      intervention to reduce aggression in bars. A total of 734 pre - post-intervention
      observations were conducted by trained observers on Friday and Saturday nights
      between midnight and 2 a.m. in 18 large capacity ( > 300) Toronto bars and clubs
      assigned randomly to receive the intervention (69% participation rate of the 26
      assigned) and 12 control bars. As part of the intervention, owners/managers
      completed the risk assessment workbook to identify ways of reducing environmental
      risks, and 373 staff and owners/managers (84% participation rate) attended a 3
      hour training session focused on preventing escalation of aggression, working as
      a team and resolving problem situations safely. The main outcome measures were
      rates of severe aggression (e.g. punching, kicking) and moderate physical
      aggression (e.g. shoving, grappling). Hierarchical linear modelling (HLM)
      comparing pre - post aggression for intervention versus control bars indicated a
      significant effect of the intervention in reducing severe and moderate
      aggression. This effect was moderated by turnover of managers and door/security
      staff with higher post-intervention aggression associated with higher turnover in
      the intervention bars. The findings indicate the potential for a stand-alone
      relatively brief intervention to reduce severe and moderate physical aggression
      in bars.

PMID- 14965886
TI  - Effects of alcohol controls: Nordic research traditions.
AB  - Drawing on a recent review of studies of the impact of alcohol control changes in
      the Nordic countries (particularly Finland, Norway and Sweden), this paper
      reviews the development of research traditions of such studies in the Nordic
      countries. From the Nordic experience, there is evidence of variation in the
      effects of policy changes by demographic segment, by type of problem and by
      drinking pattern and amount. Policy changes have often had their greatest effect
      on heavier drinkers. Big reductions in alcohol taxes in Denmark in 2003 and
      Finland in 2004 offer a new chance to study whose drinking changes how much, and
      in what contexts, in a collaborative study comparing northern Sweden with
      Finland, Denmark and southern Sweden.

PMID- 14965887
TI  - Alignment of the policy planets: behind the implementation of the Northern
      Territory (Australia) Living With Alcohol programme.
AB  - The Northern Territory Living With Alcohol Programme (LWAP), implemented in
      Australia from 1991 to 2000, has been hailed as a successful example of a
      comprehensive public health alcohol policy, especially in its first 4 years-
      1991/92 to 1995/96. This paper draws upon a policy analysis of the LWAP currently
      in progress to identify and describe the factors that made implementation
      possible at this time. I argue that programme implementation was shaped by a
      remarkable alignment of agencies and actors in the political, fiscal,
      administrative and industrial domains. This alignment of forces, however, owed as
      much to contingency as to planning and did not endure. Although the policy itself
      remained unchanged and continued to generate significant achievements, the
      alignment of forces sustaining it began to fragment from late 1995 onwards. The
      paper concludes by exploring the implications of the analysis for alcohol policy
      in other domains, and for the relationship between evidence regarding
      effectiveness and other components of the policy process.

PMID- 14965888
TI  - Risk and protection factors for different intensities of adolescent substance
      use: when does the Prevention Paradox apply?
AB  - The 'Prevention Paradox' applies when low-risk individuals in a population
      contribute the most cases of a condition or problem behaviour by virtue of their
      being in the majority, thereby recommending a universal or whole of population
      approach to prevention. The applicability of a universal as opposed to a targeted
      high-risk approach to the prevention of youth substance use was examined in two
      studies of children and adolescents conducted in Victoria, Australia. These
      studies were reanalysed by recombining developmental, social and individual
      measures to form cumulative risk indices for substance use. In Study 1, a cross
      sectional survey of students, most regular tobacco, alcohol and cannabis use by
      15/16-year-olds occurred in the moderate and low-risk groups, recommending a
      universal prevention strategy. However, the majority of illicit drug use occurred
      in the highest-risk group (top 15%). Furthermore, in younger age groups both
      legal and illegal drug use was concentrated mainly in the highest risk group.
      Study 2 used data from a major longitudinal study where risk factors at around
      age 11/12 years were used to predict substance use at age 17/18 years. Most
      students who admitted involvement in frequent smoking, heavy drinking and,
      although to a lesser degree, cannabis were classified as low or average risk. It
      is concluded that universal prevention strategies are needed for late adolescent
      alcohol, tobacco and cannabis use and more targeted strategies for addressing
      harm related to early age drug use, frequent cannabis use and illegal drug use.

PMID- 14965889
TI  - What we can--and cannot--expect from school-based drug prevention.
AB  - School-based drug prevention is a central component of drug control strategies.
      This paper assesses quantitatively its contributions in the United States from a
      social policy perspective. The social benefits per participant stemming from
      reduced drug use ( approximately $840 from tobacco, alcohol, cocaine and
      marijuana) appear to exceed the economic costs of running the programs (
      approximately $150 per participant); while the benefits associated with reduced
      cocaine use alone ( approximately $300) exceed the costs, the corresponding
      figure for marijuana ( approximately $20) is small. Even if prevention reduced
      the use of other illicit drugs (e.g. heroin) by as much as it reduced use of
      cocaine, the majority of benefits would still stem from reductions in use of
      tobacco and alcohol, which has implications for how school-based drug prevention
      is funded and whether it is perceived more as a weapon in the war on illicit
      drugs or as a public health measure. Specific numeric results are subject to
      considerable uncertainty, but the basic character of the conclusions appears to
      be robust with respect to parameter uncertainty. The greatest uncertainties
      concern the permanence of prevention's effects and how to value instances of
      initiation being deferred but not completely prevented.

PMID- 14965890
TI  - Encouraging practitioners to use resources: evaluation of the national
      implementation of a resource to improve the clinical management of alcohol
      related problems in Indigenous primary care settings.
AB  - This paper reports on the evaluation of the implementation of the National
      Recommendations for the Clinical Management of Alcohol-Related Problems in
      Indigenous Primary Care Settings undertaken in 2001 through 74 standardized
      workshops, which sought to determine: (1) whether this approach to implementation
      influenced the likelihood that the National Recommendations would be used; (2)
      whether it influenced participants' willingness to engage with Indigenous
      patients regarding alcohol-related issues; and (3) whether the implementation as
      a whole influenced both practice and clinicians' willingness to engage.
      Evaluation included pre-/post-workshop and follow-up questionnaires and a focus
      group. The findings presented indicate that distribution of clinical resources
      alone is not sufficient to ensure use and that, particularly for medical
      practitioners, appropriate introduction not only increases use but also
      positively influences willingness to engage with alcohol-related problems as part
      of primary clinical care. Further, the enthusiasm for guideline production should
      be tempered by the need to develop effective implementation strategies.

PMID- 14965891
TI  - Smoking behaviour among Indigenous secondary school students in North Queensland.
AB  - This study investigated smoking behaviour among Indigenous youth. A sample of
      schools (n = 12) in north Queensland with large proportions of Indigenous
      students was selected. Details about the prevalence of smoking behaviour in both
      Indigenous and non-Indigenous students (n = 883) were gathered. Data were also
      collected on the cultural, social, and psychological factors associated with
      cigarette smoking for Indigenous and non-Indigenous students. This survey
      indicated smoking rates for Indigenous and non-Indigenous students were 24% and
      30%, respectively. The study found similarities between both groups regarding
      where they obtained their cigarettes (friends) and their reasons for not smoking
      (their parents and health). Results of this survey challenge the belief that
      Indigenous youth are significantly different in their smoking patterns and
      behaviours compared to non-Indigenous secondary school students in rural regions.
      It indicated the potential importance of school communities in promoting non
      smoking behaviours among Indigenous students even in the face of strong normative
      pressures from elsewhere in the community. This survey can be used to monitor
      smoking prevalence among Indigenous secondary students in north Queensland, help
      guide the development of culturally appropriate school curriculum resources and
      contribute to the overall evaluation of smoking prevention and smoking cessation
      programs which are developed for Indigenous secondary school students.

PMID- 14965892
TI  - Heroin users in Australia: population trends.
AB  - The aim of this paper is to identify certain important population trends among
      heroin users in Australia for the period 1971 - 97, such as: population growth,
      initiation, i.e. the number who were initiated to heroin in a given year, and
      quitting, i.e. the number that quit using heroin. For this purpose, we summarize
      and extract relevant characteristics from data from National Drug Strategy
      Household Survey (NDSHS 1998) conducted in Australia in 1998. We devise a
      systematic procedure to estimate historical trends from questions concerning past
      events. It is observed from our findings that the size of the heroin user
      population in Australia is in a sharp increase, especially from the early 1980s
      onwards. The general trend obtained for the period 1971 - 97 is strikingly
      similar to that obtained by Hall et al. (2000) for the dependent heroin user
      population in Australia, even though their study was based on different datasets
      and a different methodology. In our reconstruction of the time history we also
      detect a levelling-off prior to 1990. Initiation is also observed to be on a
      sharp increase. The latter trend is accompanied by a similar trend of quitting,
      perhaps indicating a relatively short heroin use career. A sharp decrease in both
      initiation and quitting is observed after 1990. In conclusion, in the case of the
      trend in the population of heroin users a high rate of growth has been identified
      that is consistent with the existing literature. In the process, we demonstrated
      that even a static survey such as NDSHS 1998 can, sometimes, be used to extract
      historical (dynamic) trends of certain important variables.

PMID- 14965893
TI  - Policy approaches to support local community control over the supply and
      distribution of kava in the Northern Territory (Australia).
AB  - The health consequences of kava abuse in Arnhem Land Aboriginal populations in
      the Northern Territory (NT) and the persistence of an illegal kava trade with its
      associated social harms have been a cause for concern for 20 years. Despite these
      concerns, some Arnhem Land groups seek to continue using kava and to control its
      sale, distribution and the profits from the enterprise. In response, policy
      makers in the NT have embraced principles of harm reduction and created
      regulatory mechanisms to address broader public concerns and to support local
      management of kava supply while reinforcing control over the consequences of its
      use. This paper describes the kava regulatory system now being implemented in the
      NT which features kava management plans developed in consultation between
      Aboriginal communities and licensing authorities. It complements the earlier Harm
      Reduction Digest 9 by McDonald & Jowitt which looked at Kava in the South
      Pacific.

PMID- 14965895
TI  - Asia Pacific Column. Announcement of column on capacity building in the Asia
      Pacific region.

PMID- 14965896
TI  - Complex data produce better characters.
AB  - Two studies were conducted to explore the use of complex data in character
      description and hybrid identification. In order to determine if complex data
      allow the production of better characters, eight groups of plant systematists
      were given two classes of drawings of plant parts, and asked to divide them into
      character states (clusters) in two separate experiments. The first class of
      drawings consisted only of cotyledons. The second class consisted of triplets of
      drawings: a cotyledon, seedling leaf, and inflorescence bract. The triplets were
      used to simulate complex data such as might be garnered by looking at a plant.
      Each experiment resulted in four characters (groups of clusters), one for each
      group of systematists. Visual and statistical analysis of the data showed that
      the systematists were able to produce smaller, more precisely defined character
      states using the more complex drawings. The character states created with the
      complex drawings also were more consistent across systematists, and agreed more
      closely with an independent assessment of phylogeny. To investigate the utility
      of complex data in an applied task, four observers rated 250 hybrids of Dubautia
      ciliolata X arborea based on the overall form (Gestalt) of the plants, and took
      measurements of a number of features of the same plants. A composite score of the
      measurements was created using principal components analysis. The correlation
      between the scores on the first principal component and the Gestalt ratings was
      computed. The Gestalt ratings and PC scores were significantly correlated,
      demonstrating that assessments of overall similarity can be as useful as more
      conventional approaches in determining the hybrid status of plants.

PMID- 14965897
TI  - Out of Africa: the slow train to australasia.
AB  - We used mitochondrial DNA (mtDNA) sequences to test biogeographic hypotheses for
      Patiriella exigua (Asterinidae), one of the world's most widespread coastal sea
      stars. This small intertidal species has an entirely benthic life history and yet
      occurs in southern temperate waters of the Atlantic, Indian, and Pacific oceans.
      Despite its abundance around southern Africa, southeastern Australia, and several
      oceanic islands, P. exigua is absent from the shores of Western Australia, New
      Zealand, and South America. Phylogenetic analysis of mtDNA sequences (cytochrome
      oxidase I, control region) indicates that South Africa houses an assemblage of P.
      exigua that is not monophyletic (P = 0.04), whereas Australian and Lord Howe
      Island specimens form an interior monophyletic group. The placement of the root
      in Africa and small genetic divergences between eastern African and Australian
      haplotypes strongly suggest Pleistocene dispersal eastward across the Indian
      Ocean. Dispersal was probably achieved by rafting on wood or macroalgae, which
      was facilitated by the West Wind Drift. Genetic data also support Pleistocene
      colonization of oceanic islands (Lord Howe Island, Amsterdam Island, St. Helena).
      Although many biogeographers have speculated about the role of long-distance
      rafting, this study is one of the first to provide convincing evidence. The
      marked phylogeographic structure evident across small geographic scales in
      Australia and South Africa indicates that gene flow among populations may be
      generally insufficient to prevent the local evolution of monophyly. We suggest
      that P. exigua may rely on passive mechanisms of dispersal.

PMID- 14965898
TI  - Reticulate evolution, introgression, and intertribal gene capture in an
      allohexaploid grass.
AB  - Recent molecular phylogenetic studies of polyploid plants have successfully
      clarified complex patterns of reticulate evolution. In this study of Elymus
      repens, an allohexaploid member of the wheat tribe Triticeae, chloroplast and
      nuclear DNA data reveal an extreme reticulate pattern, revealing at least five
      distinct gene lineages coexisting within the species, acquired through a possible
      combination of allohexaploidy and introgression from both within and beyond the
      Triticeae. Earlier cytogenetic studies of E. repens suggested that Hordeum
      (genome H) and Pseudoroegneria (St) were genome donors to E. repens. Chloroplast
      DNA data presented here (from the rpoA gene and from the region between trnT and
      trnF) identify three potential maternal genome donors (Pseudoroegneria,
      Thinopyrum, and Dasypyrum), and information from previous molecular work suggests
      that, of these, Pseudoroegneria is the most likely maternal donor. Nuclear starch
      synthase gene data indicate that both Hordeum and Pseudoroegneria have
      contributed to the nuclear genome of E. repens, in agreement with cytogenetic
      data. However, these data also show unexpected contributions from Taeniatherum,
      and from two additional donors of unknown identity. One of the sequences of
      unknown origin falls within the Triticeae, but is not closely associated with any
      of the sampled diploid genera. The second falls outside of the clade containing
      Triticeae and its outgroup Bromus, suggesting the acquisition of genetic material
      from a surprisingly divergent source. Bias toward the amplification of certain
      starch synthase variants has complicated attempts to thoroughly sample from
      within individuals, but the data clearly indicate a complex pattern of reticulate
      evolution, consistent not only with allohexaploidy, but also with introgression
      from unexpectedly divergent sources.

PMID- 14965899
TI  - Sampling properties of the bootstrap support in molecular phylogeny: influence of
      nonindependence among sites.
AB  - The influence of nonindependence among sites on phylogenetic reconstructions and
      bootstrap scores was investigated both analytically and empirically. First, the
      sampling properties of the bootstrap support in the four-species case was derived
      for the maximum-parsimony method, assuming either independently or
      nonindependently evolving sites. The influence of various models of departure
      from the independence assumption was quantified. Second, trees and bootstrap
      scores estimated from subsets of consecutive (potentially coevolving) versus
      dispersed (presumably independent) sites of a ribosomal RNA data set were
      contrasted. The two approaches consistently suggest that a departure from the
      assumption of independent sites tends to reduce the amount of phylogenetic
      information contained in the data, but to increase the apparent statistical
      support for reconstructed trees, as measured by the bootstrap. In particular,
      nonindependence can lead to strongly supported wrong internal branches.

PMID- 14965900
TI  - Bayesian phylogenetic analysis of combined data.
AB  - The recent development of Bayesian phylogenetic inference using Markov chain
      Monte Carlo (MCMC) techniques has facilitated the exploration of parameter-rich
      evolutionary models. At the same time, stochastic models have become more
      realistic (and complex) and have been extended to new types of data, such as
      morphology. Based on this foundation, we developed a Bayesian MCMC approach to
      the analysis of combined data sets and explored its utility in inferring
      relationships among gall wasps based on data from morphology and four genes
      (nuclear and mitochondrial, ribosomal and protein coding). Examined models range
      in complexity from those recognizing only a morphological and a molecular
      partition to those having complex substitution models with independent parameters
      for each gene. Bayesian MCMC analysis deals efficiently with complex models:
      convergence occurs faster and more predictably for complex models, mixing is
      adequate for all parameters even under very complex models, and the parameter
      update cycle is virtually unaffected by model partitioning across sites.
      Morphology contributed only 5% of the characters in the data set but nevertheless
      influenced the combined-data tree, supporting the utility of morphological data
      in multigene analyses. We used Bayesian criteria (Bayes factors) to show that
      process heterogeneity across data partitions is a significant model component,
      although not as important as among-site rate variation. More complex evolutionary
      models are associated with more topological uncertainty and less conflict between
      morphology and molecules. Bayes factors sometimes favor simpler models over
      considerably more parameter-rich models, but the best model overall is also the
      most complex and Bayes factors do not support exclusion of apparently weak
      parameters from this model. Thus, Bayes factors appear to be useful for selecting
      among complex models, but it is still unclear whether their use strikes a
      reasonable balance between model complexity and error in parameter estimates.

PMID- 14965901
TI  - Meaning of the name tetrapoda in the scientific literature: an exchange.

PMID- 14965902
TI  - Congruence versus phylogenetic accuracy: revisiting the incongruence length
      difference test.

PMID- 14965904
TI  - Untangling coevolutionary history.

PMID- 14965905
TI  - Host-symbiont stability and fast evolutionary rates in an ant-bacterium
      association: cospeciation of camponotus species and their endosymbionts,
      candidatus blochmannia.
AB  - Bacterial endosymbionts are widespread across several insect orders and are
      involved in interactions ranging from obligate mutualism to reproductive
      parasitism. Candidatus Blochmannia gen. nov. (Blochmannia) is an obligate
      bacterial associate of Camponotus and related ant genera (Hymenoptera:
      Formicidae). The occurrence of Blochmannia in all Camponotus species sampled from
      field populations and its maternal transmission to host offspring suggest that
      this bacterium is engaged in a long-term, stable association with its ant hosts.
      However, evidence for cospeciation in this system is equivocal because previous
      phylogenetic studies were based on limited gene sampling, lacked statistical
      analysis of congruence, and have even suggested host switching. We compared
      phylogenies of host genes (the nuclear EF-1alphaF2 and mitochondrial COI/II) and
      Blochmannia genes (16S ribosomal DNA [rDNA], groEL, gidA, and rpsB), totaling
      more than 7 kilobases for each of 16 Camponotus species. Each data set was
      analyzed using maximum likelihood and Bayesian phylogenetic reconstruction
      methods. We found minimal conflict among host and symbiont phylogenies, and the
      few areas of discordance occurred at deep nodes that were poorly supported by
      individual data sets. Concatenated protein-coding genes produced a very well
      resolved tree that, based on the Shimodaira-Hasegawa test, did not conflict with
      any host or symbiont data set. Correlated rates of synonymous substitution (d(S))
      along corresponding branches of host and symbiont phylogenies further supported
      the hypothesis of cospeciation. These findings indicate that Blochmannia
      Camponotus symbiosis has been evolutionarily stable throughout tens of millions
      of years. Based on inferred divergence times among the ant hosts, we estimated
      rates of sequence evolution of Blochmannia to be approximately 0.0024
      substitutions per site per million years (s/s/MY) for the 16S rDNA gene and
      approximately 0.1094 s/s/MY at synonymous positions of the genes sampled. These
      rates are several-fold higher than those for related bacteria Buchnera aphidicola
      and Escherichia coli. Phylogenetic congruence among Blochmannia genes indicates
      genome stability that typifies primary endosymbionts of insects.

PMID- 14965906
TI  - Evolutionary relationships, cospeciation, and host switching in avian malaria
      parasites.
AB  - We used phylogenetic analyses of cytochrome b sequences of malaria parasites and
      their avian hosts to assess the coevolutionary relationships between host and
      parasite lineages. Many lineages of avian malaria parasites have broad host
      distributions, which tend to obscure cospeciation events. The hosts of a single
      parasite or of closely related parasites were nonetheless most frequently
      recovered from members of the same host taxonomic family, more so than expected
      by chance. However, global assessments of the relationship between parasite and
      host phylogenetic trees, using Component and ParaFit, failed to detect
      significant cospeciation. The event-based approach employed by TreeFitter
      revealed significant cospeciation and duplication with certain cost assignments
      for these events, but host switching was consistently more prominent in matching
      the parasite tree to the host tree. The absence of a global cospeciation signal
      despite conservative host distribution most likely reflects relatively frequent
      acquisition of new hosts by individual parasite lineages. Understanding these
      processes will require a more refined species concept for malaria parasites and
      more extensive sampling of parasite distributions across hosts. If parasites can
      disperse between allopatric host populations through alternative hosts,
      cospeciation may not have a strong influence on the architecture of host-parasite
      relationships. Rather, parasite speciation may happen more often in conjunction
      with the acquisition of new hosts followed by divergent selection between host
      lineages in sympatry. Detailed studies of the phylogeographic distributions of
      hosts and parasites are needed to characterize these events.

PMID- 14965907
TI  - Plant-insect interactions: double-dating associated insect and plant lineages
      reveals asynchronous radiations.
AB  - An increasing number of plant-insect studies using phylogenetic analysis suggest
      that cospeciation events are rare in plant-insect systems. Instead, nonrandom
      patterns of phylogenetic congruence are produced by phylogenetically conserved
      host switching (to related plants) or tracking of particular resources or traits
      (e.g., chemical). The dominance of host switching in many phytophagous insect
      groups may make the detection of genuine cospeciation events difficult. One
      important test of putative cospeciation events is to verify whether reciprocal
      speciation is temporally plausible. We explored techniques for double-dating of
      both plant and insect phylogenies. We use dated molecular phylogenies of a
      psyllid (Hemiptera)-Genisteae (Fabaceae) system, a predominantly monophagous
      insect-plant association widespread on the Atlantic Macaronesian islands.
      Phylogenetic reconciliation analysis suggests high levels of parallel
      cladogenesis between legumes and psyllids. However, dating using molecular clocks
      calibrated on known geological ages of the Macaronesian islands revealed that the
      legume and psyllid radiations were not contemporaneous but sequential. Whereas
      the main plant radiation occurred some 8 million years ago, the insect radiation
      occurred about 3 million years ago. We estimated that >60% of the psyllid
      speciation has resulted from host switching between related hosts. The only
      evidence for true cospeciation is in the much more recent and localized radiation
      of genistoid legumes in the Canary Islands, where the psyllid and legume
      radiations have been partially contemporaneous. The identification of specific
      cospeciation events over this time period, however, is hindered by the
      phylogenetic uncertainty in both legume and psyllid phylogenies due to the
      apparent rapidity of the species radiations.

PMID- 14965908
TI  - Correlated evolution in fig pollination.
AB  - This is the first comparative study of correlated evolution between figs (Ficus
      species, Moraceae) and their pollinators (Hymenoptera: Agaoninae) based on
      molecular phylogenies of both lineages. Fig relationships based on the internal
      transcribed spacer region (ITS) of nuclear ribosomal DNA and pollinator
      relationships inferred from mitochondrial cytochrome oxidase I (COI) sequences
      enabled the study of correlated evolution based on molecular phylogenies for the
      largest set of interacting species ever compared. Comparative methods have been
      applied to tests of adaptation, but the application of these methods in tests of
      coadaptation, defined as reciprocal evolutionary change in interacting lineages,
      has received less attention. I have extended tests of correlated evolution
      between two traits along a phylogeny to the case of interacting lineages, where
      two traits may or may not share a common phylogenetic history. Independent
      contrasts and phylogenetic autocorrelation rejected the null hypothesis that
      trait correlations within lineages are stronger than trait correlations between
      interacting lineages. Fig style lengths and pollinator ovipositor lengths, for
      example, were more highly correlated than were pollinator body size and
      ovipositor length. Mutualistic interactions between figs and their pollinators
      illustrate the novel ways in which phylogenies and comparative methods can detect
      patterns of correlated evolution. The most outstanding evidence of correlated
      evolution between these obligate mutualists is that interacting trait
      correlations are stronger than within-lineage allometric relationships.

PMID- 14965909
TI  - Clade-limited colonization in brood parasitic finches (Vidua spp.).
AB  - The African brood parasitic finches (Vidua spp.) are host specialists that mimic
      the songs and nestling mouth markings of their finch hosts (family Estrildidae).
      Although recent molecular analyses suggest rapid speciation associated with host
      switches in some members of this group, the association of different Vidua
      lineages with particular host genera suggests the possibility of cospeciation at
      higher levels in the host and parasite phylogenies. We compared a phylogeny of
      all Vidua species with a phylogeny of their estrildid finch hosts and compared
      divergence time estimates for the two groups. Basal divergences among extant
      members of the Vidulidae and among Vidua species are more recent than those among
      host genera and species, respectively, allowing a model of cospeciation to be
      rejected at most or all levels of the Vidua phylogeny. Nonetheless, some tests
      for cospeciation indicated significant congruence between host and parasite tree
      topologies. This result may be an artifact of clade-limited colonization. Host
      switches in parasitic finches have most often involved new hosts in the same or a
      closely related genus, an effect that increases the apparent congruence of host
      and parasites trees.

PMID- 14965910
TI  - Biogeography explains cophylogenetic patterns in toucan chewing lice.
AB  - Historically, comparisons of host and parasite phylogenies have concentrated on
      cospeciation. However, many of these comparisons have demonstrated that the
      phylogenies of hosts and parasites are seldom completely congruent, suggesting
      that phenomena other than cospeciation play an important role in the evolution of
      host-parasite assemblages. Other coevolutionary phenomena, such as host
      switching, parasite duplication (speciation on the host), sorting (extinction),
      and failure to speciate can also influence host-parasite assemblages. Using
      mitochondrial and nuclear protein-coding DNA sequences, I reconstructed the
      phylogeny of ectoparasitic toucan chewing lice in the Austrophilopterus
      cancellosus subspecies complex and compared this phylogeny with the phylogeny of
      the hosts, the Ramphastos toucans, to reconstruct the history of coevolutionary
      events in this host-parasite assemblage. Three salient findings emerged. First,
      reconstructions of host and louse phylogenies indicate that they do not branch in
      parallel, and their cophylogenetic history shows little or no significant
      cospeciation. Second, members of monophyletic Austrophilopterus toucan louse
      lineages are not necessarily restricted to monophyletic host lineages. Often,
      closely related lice are found on more distantly related but sympatric toucan
      hosts. Third, the geographic distribution of the hosts apparently plays a role in
      the speciation of these lice. These results suggest that for some louse lineages
      biogeography may be more important than host associations in structuring louse
      populations and species, particularly when host life history (e.g., hole nesting)
      or parasite life history (e.g., phoresis) might promote frequent host switching
      events between syntopic host species. These findings highlight the importance of
      integrating biogeographic information into cophylogenetic studies.

PMID- 14965911
TI  - Ecology of congruence: past meets present.
AB  - Phylogenetic congruence is governed by various macroevolutionary events,
      including cospeciation, host switching, sorting, duplication, and failure to
      speciate. The relative frequency of these events may be influenced by factors
      that govern the distribution and abundance of the interacting groups; i.e.,
      ecological factors. If so, it may be possible to predict the degree of
      phylogenetic congruence between two groups from information about their ecology.
      Unfortunately, adequate comparative ecological data are not available for many of
      the systems that have been subjected to cophylogenetic analysis. An exception is
      provided by chewing lice (Insecta: Phthiraptera), which parasitize birds and
      mammals. For a few genera of these lice, enough data have now been published to
      begin exploring the relationship between ecology and congruence. In general,
      there is a correspondence between important ecological factors and the degree of
      phylogenetic congruence. Careful comparison of these genera suggests that
      dispersal is a more fundamental barrier to host switching among related hosts
      than is establishment. Transfer experiments show that host-specific lice can
      survive and reproduce on novel hosts that are similar in size to the native host
      as long as the lice can disperse to these hosts. To date, studies of parasite
      dispersal have been mainly inferential. A better understanding of the role of
      dispersal will require more direct data on dispersal frequency and distances.

PMID- 14965913
TI  - Relationships between stem diameter, sapwood area, leaf area and transpiration in
      a young mountain ash forest.
AB  - We examined relationships between stem diameter, sapwood area, leaf area and
      transpiration in a 15-year-old mountain ash (Eucalyptus regnans F. Muell.) forest
      containing silver wattle (Acacia dealbata Link.) as a suppressed overstory
      species and mountain hickory (Acacia frigescens J.H. Willis) as an understory
      species. Stem diameter explained 93% of the variation in leaf area, 96% of the
      variation in sapwood area and 88% of the variation in mean daily spring
      transpiration in 19 mountain ash trees. In seven silver wattle trees, stem
      diameter explained 87% of the variation in sapwood area but was a poor predictor
      of the other variables. When transpiration measurements from individual trees
      were scaled up to a plot basis, using stem diameter values for 164 mountain ash
      trees and 124 silver wattle trees, mean daily spring transpiration rates of the
      two species were 2.3 and 0.6 mm day(-1), respectively. The leaf area index of the
      plot was estimated directly by destructive sampling, and indirectly with an LAI
      2000 plant canopy analyzer and by hemispherical canopy photography. All three
      methods gave similar results.

PMID- 14965914
TI  - Growth and water relations of three geographically separate origins of maritime
      pine (Pinus pinaster) under saline conditions.
AB  - Water relations and growth of maritime pine (Pinus pinaster Ait.) were
      investigated in 2-year-old seedlings of French ('Landes'), Iberian ('Iberian')
      and Moroccan ('Tamjoute') origin raised for 67 days in a flowing solution culture
      system containing 0, 50, 150 or 250 mM NaCl. Height growth, and stem, needle and
      root dry matter were reduced by salinity with minor differences among geographic
      origins. Predawn needle water potential was decreased by salinity and
      corresponded approximately to the osmotic potential of the nutrient solution.
      Stomatal conductance was reduced according to the amount of salinity applied.
      Whole-plant hydraulic conductance was also reduced, even when expressed on a root
      dry weight basis. The osmotic potential of xylem sap was five- to sixfold lower
      than that of the nutrient solution. Seedlings of the most southerly origin
      (Tamjoute) exhibited a greater ability to decrease osmotic potential under saline
      conditions than seedlings of more northerly origin (Landes and Iberian) as a
      result of higher mineral cation transport to the shoot.

PMID- 14965915
TI  - The influence of magnesium deficiency on carbohydrate concentrations in Norway
      spruce (Picea abies) needles.
AB  - Both short- and long-term effects of Mg deficiency on carbohydrate metabolism
      were investigated in 6-year-old clonal Norway spruce (Picea abies (L.) Karst.)
      trees cultivated in sand culture with an optimal supply of nutrients, except for
      Mg which was supplied at 0.203, 0.041 and 0.005 mM to provide optimal, moderately
      deficient and severely deficient Mg supply, respectively. Annual changes in
      carbohydrate concentrations (starch, sucrose, glucose and fructose) were analyzed
      and diurnal changes were investigated on a single day during the summer. Older
      needles of trees in the moderate Mg-deficiency treatment developed tip-yellowing
      symptoms, whereas current-year needles remained green. The severe Mg-deficiency
      treatment led to pronounced yellowing symptoms in needles of all ages. Increased
      carbohydrate concentrations were observed before needle yellowing occurred.
      Diurnal and annual changes in carbohydrates were similar in all treatments;
      however, carbohydrate concentrations were influenced by Mg supply. In both Mg
      deficiency treatments, starch concentrations increased in needles, especially
      during summer and autumn. Starch accumulation was more pronounced at the
      beginning of the Mg-deficiency treatments than at the end of the treatments.
      Sucrose, and to a minor extent, glucose and fructose concentrations tended to
      increase in response to Mg deficiency. The consequences of Mg deficiency on
      carbohydrate metabolism are discussed with respect to reduced plant growth and
      decreased transport rates of carbohydrates to sink organs.

PMID- 14965916
TI  - Photosynthetic productivity of aspen clones varying in sensitivity to
      tropospheric ozone.
AB  - Rooted cuttings from three aspen (Populus tremuloides Michx.) clones (216, 271
      and 259, classified as high, intermediate and low in O(3) tolerance,
      respectively) were exposed to either diurnal O(3) profiles simulating those of
      Michigan's Lower Peninsula (episodic treatments), or diurnal square-wave O(3)
      treatments in open-top chambers in northern Michigan, USA. Ozone was dispensed in
      chambers ventilated with charcoal-filtered (CF) air. In addition, seedlings were
      compared to rooted cuttings in their response to episodic O(3) treatments. Early
      in the season, O(3) caused decreased photosynthetic rates in mature leaves of all
      clones, whereas only the photosynthetic rates of recently mature leaves of the
      O(3)-sensitive Clone 259 decreased in response to O(3) exposure. During
      midseason, O(3) caused decreased photosynthetic rates of both recently mature and
      mature leaves of the O(3)-sensitive Clone 259, but it had no effect on the
      photosynthetic rate of recently mature leaves of the O(3)-tolerant Clone 216.
      Late in the season, however, photosynthetic rates of both recently mature and
      mature leaves of Clone 216 were lower than those of the control plants maintained
      in CF air. Ozone decreased the photosynthetic rate of mature leaves of Clone 271,
      but it increased or had no effect on the photosynthetic rate of recently mature
      leaves. Photosynthetic response patterns of seedlings to O(3) treatment were
      similar to those of the clones, but total magnitude of the response was less,
      perhaps reflecting the diverse genotypes of the seedling population. Early leaf
      abscission was observed in all clones exposed to O(3); however, Clones 216 and
      259 lost more leaf area than Clone 271. By late August, leaf area in the highest
      O(3) treatment had decreased relative to the controls by 26, 24 and 9% for Clones
      216, 259 and 271, respectively. Ozone decreased whole-tree photosynthesis in all
      clones, and the decrease was consistently less in Clone 271 (23%) than in Clones
      216 (56%) and 259 (56%), and was accompanied by declines in total biomass of 19,
      28 and 47%, respectively. The relationship between biomass and whole-tree
      photosynthesis indicates that the negative impact of O(3) on biomass in the
      clones was determined largely by lower photosynthetic productivity of the
      foliage, rather than by potential changes in the carbon relations of other plant
      organs.

PMID- 14965918
TI  - Aluminum sensitivity of loblolly pine and slash pine seedlings grown in solution
      culture.
AB  - To probe variation in Al sensitivity of two co-occurring pine species, seedlings
      from six full-sib families of loblolly pine (Pinus taeda L.) and slash pine
      (Pinus elliottii Engelm.) were grown in solution culture containing 4.4 mM (high
      Al) or 0.01 mM (low-Al) AlCl(3) at pH 4 for 58 days. On average, both pine
      species had 41% less total dry weight in the high-Al treatment than in the low-Al
      treatment. Stem volume growth of slash pine was more sensitive to the high-Al
      treatment than that of loblolly pine. In both species, the high-Al treatment
      inhibited root dry weight more than shoot dry weight. Within-species variation in
      Al sensitivity among families was greater in loblolly pine (24 to 52% inhibition
      of seedling dry weight) than in slash pine (35 to 47% inhibition of seedling dry
      weight). Foliar Al concentration was positively correlated with Al sensitivity in
      slash pine but not in loblolly pine; however, in both species, the concentration
      of Al in roots was 20-fold greater than in foliage.

PMID- 14965917
TI  - Carbon allocation and partitioning in aspen clones varying in sensitivity to
      tropospheric ozone.
AB  - Clones of aspen (Populus tremuloides Michx.) were identified that differ in
      biomass production in response to O(3) exposure. (14)Carbon tracer studies were
      used to determine if the differences in biomass response were linked to shifts in
      carbon allocation and carbon partitioning patterns. Rooted cuttings from three
      aspen Clones (216, O(3) tolerant; 271, intermediate; and 259, O(3) sensitive)
      were exposed to either charcoal-filtered air (CF) or an episodic, two-times
      ambient O(3) profile (2x) in open-top chambers. Either recently mature or mature
      leaves were exposed to a 30-min (14)C pulse and returned to the treatment
      chambers for a 48-h chase period before harvest. Allocation of (14)C to different
      plant parts, partitioning of (14)C into various chemical fractions, and the
      concentration of various chemical fractions in plant tissue were determined. The
      percent of (14)C retained in recently mature source leaves was not affected by
      O(3) treatment, but that retained in mature source leaves was greater in O(3)
      treated plants than in CF-treated plants. Carbon allocation from source leaves
      was affected by leaf position, season, clone and O(3) exposure. Recently mature
      source leaves of CF-treated plants translocated about equal percentages of (14)C
      acropetally to growing shoots and basipetally to stem and roots early in the
      season. When shoot growth ceased (August 16), most (14)C from all source leaves
      was translocated basipetally to stem and roots. At no time did mature source
      leaves allocate more than 6% of (14)C translocated within the plant to the shoot
      above. Ozone effects were most apparent late in the season. Ozone decreased the
      percent (14)C translocated from mature source leaves to roots and increased the
      percent (14)C translocated to the lower stem. In contrast, allocation from
      recently mature leaves to roots increased. Partitioning of (14)C among chemical
      fractions was affected by O(3) more in source leaves than in sink tissue. In
      source leaves, more (14)C was incorporated into the sugar, organic acid and
      lipids + pigments fractions, and less (14)C was incorporated into starch and
      protein fractions in O(3)-treated plants than in CF-treated plants. In addition,
      there were O(3) treatment interactions between leaf position and clones for (14)C
      incorporation into different chemical fractions. When photosynthetic data were
      used to convert percent (14)C transported to the total amount of carbon
      transported on a mass basis, it was found that carbon transport was controlled
      more by photosynthesis in the source leaves than proportional changes in
      allocation to the sinks. Ozone decreased the total amount of carbon translocated
      to all sink tissue in the O(3)-sensitive Clone 259 because of decreases in
      photosynthesis in both recently mature and mature source leaves. In contrast,
      O(3) had no effect on carbon transport from recently mature leaves to lower
      shoots of either Clone 216 or 271, had no significant effect on transport to
      roots of Clone 216, and increased transport to roots of Clone 271. The O(3)
      induced increase in transport to roots of Clone 271 was the result of a
      compensatory increase in upper leaf photosynthesis and a relatively greater shift
      in the percent of carbon allocated to roots. In contrast to those of Clone 271,
      recently mature leaves of Clone 216 maintained similar photosynthetic rates and
      allocation patterns in both the CF and O(3) treatments. We conclude that Clone
      271 was more tolerant to O(3) exposure than Clone 216 or 259. Tolerance to
      chronic O(3) exposure was directly related to maintenance of high photosynthetic
      rates in recently mature leaves and retention of lower leaves.

PMID- 14965919
TI  - Water deficits at anthesis reduce CO(2) assimilation and yield of lychee (Litchi
      chinensis Sonn.) trees.
AB  - Ten-year-old 'Tai So' lychee (Litchi chinensis Sonn.) trees growing on a sandy
      loam soil in subtropical South Africa (latitude 25 degrees S) were watered weekly
      (well-watered treatment) or droughted from late July until January (drought
      treatment). After 16 weeks, at which time the trees obtained most of their water
      from below 150 cm, average soil water content at 0 to 150 cm depth was 14.5 +/-
      0.1% in the well-watered treatment and reached a minimum of 7.6% in the drought
      treatment. At Week 7, minimum leaf water potential (Psi(L)) in the morning and
      early afternoon declined to -2.6 and -2.8 MPa, respectively, in droughted trees
      compared with -1.5 and -2.2 MPa, respectively, in well-watered trees. From Week
      9, stomatal conductance and net CO(2) assimilation rate ranged from 70 to 300
      mmol m(-2) s(-1) and 3 to 13 micro mol CO(2) m(-2) s(-1), respectively, in well
      watered trees. The corresponding values for droughted trees were 50 to 180 mmol
      m(-2) s(-1) and 2 to 6 micro mol CO(2) m(-2) s(-1). Five weeks after rewatering
      the droughted trees, gas exchange had not recovered to the rate in well-watered
      trees, although tree water status recovered within a week of rewatering. In the
      well-watered trees, water use (E(t)) was 26 +/- 1 mm week(-1) with evaporation
      (E(p)) of 20 to 70 mm week(-1) indicating a crop factor (k(c) = E(t)/E(p)) of 0.4
      to 1.2. Before anthesis, tree water status did not affect extension growth of
      floral panicles or leafy shoots. In contrast, no vegetative shoots were initiated
      after fruit set in the droughted trees when Psi(L) in the morning declined to 
      2.5 MPa. Water deficits reduced initial fruit set by 30% and final fruit set by
      70% as a result of fruit splitting (41.2 +/- 4.0% versus 10.0 +/- 1.3%). Water
      deficits did not alter the sigmoidal pattern of fruit growth, but reduced yield
      from 51.4 +/- 5.5 kg tree(-1) in well-watered trees to 7.4 +/- 3.3 kg tree(-1) in
      droughted trees.

PMID- 14965920
TI  - Characterization of the induced response of slash pine to inoculation with bark
      beetle vectored fungi.
AB  - Six 25- to 30-year-old slash pine, Pinus elliottii Englm. var. elliottii, trees
      were inoculated with Ophiostoma minus (Hedgc.) H.P. Sydow, O. ips (Rumb.) Nannf
      or sterile water. Two, 4 and 6 weeks after inoculation, the lengths of developing
      lesions and the monoterpene concentration of the necrotic tissue within each
      lesion were measured. Both sterile and fungal wounding resulted in the
      development of lesions in the phloem-outer xylem. At both 4 and 6 weeks after
      inoculation, lesions induced by O. minus were significantly larger than lesions
      induced by O. ips or sterile water, whereas the lesions induced by O. ips and
      sterile water were similar in size at all sampling periods. At 2, 4 and 6 weeks
      after inoculation, lesions induced by O. minus had significantly greater
      concentrations of monoterpenes than lesions induced by O. ips or sterile water.
      The monoterpene concentration of lesions induced by O. ips was significantly
      greater than that of lesions induced by sterile water only at the 6-week sampling
      period. Visual examination of the lesions indicated that O. minus but not O. ips
      was inhibiting the development of callus tissue, suggesting that the strain of O.
      ips was either nonpathogenic or avirulent.

PMID- 14965921
TI  - Axillary shoot proliferation in cultures of explants from mature Juniperus
      oxycedrus trees.
AB  - We developed procedures for the micropropagation of Juniperus oxycedrus L. using
      shoot apices or nodal segments from mature plants. Of the media and explants
      examined, best culture establishment was obtained with shoot apices cultured on
      modified Schenk and Hildebrandt medium (SH medium) without growth regulators;
      however, shoot multiplication was only achieved when shoot apices isolated from
      shoots grown on SH medium without growth regulators were subcultured on SH medium
      containing 0.5 micro M benzyladenine. None of the auxins and methods tested for
      root induction provided satisfactory results.

PMID- 14965922
TI  - From flower induction to seed production in forest tree orchards.
AB  - We review developments in cone and seed production research during the past
      decade. We conclude that although cone induction techniques, including hormonal
      and cultural procedures, have been refined, they still do not fully overcome
      juvenility or noninductive environmental effects. The role pollen plays in
      enhancing seed production and the genetic quality of seed is discussed.
      Techniques for handling pollen are described, in vitro viability assays are
      reviewed, and we also examine recent developments in pollen collection and its
      artificial ripening.

PMID- 14965923
TI  - Effects of irrigation, spacing and fertilization on flowering and growth in young
      Alnus rubra.
AB  - Flowering and vegetative growth were assessed in 19 half-sib families of Alnus
      rubra Bong. planted in a replicated field trial near Olympia, Washington, USA.
      The trial consisted of three square spacings (0.5, 1.0 and 2.0 m), two irrigation
      regimes (low and high), and two fertilization treatments (0 and 300 kg P ha(-1)).
      Male and female flowers were surveyed in all plots for all families at plantation
      ages 4 and 5 years. Female strobili were surveyed for seven families in the 2-m
      spaced plots at plantation age 6 years. The percentage of trees flowering and the
      number of flowers per tree were always greatest, and height and diameter growth
      were always least, in the low-irrigation regime. Phosphorus fertilization had no
      effect on the percentage of trees flowering or on 5-year height or diameter
      growth; it had a positive but small effect on the number of female flowers per
      tree at age 5 years. Wider spacing resulted in larger trees, higher rates of
      flowering, and higher tree survival. Within each irrigation regime, the
      percentage of trees flowering increased as tree size increased. There was
      substantial variation in flowering among families, with positive but low
      correlations between tree size and flowering attributes. At ages 4 and 5 years,
      the ratio of number of trees flowering in the low-irrigation regime to number of
      trees flowering in the high-irrigation regime differed among families. By age 6
      years, many more trees flowered than in previous years, and differences between
      irrigation regimes were reduced. Early growth rates were rapid and resulted in
      substantial crown recession and mortality in the closer spacings by age 5 years.
      We conclude that spacings less than 2 m should only be used in seed production
      areas if roguing can be done by age 2 to 3 years.

PMID- 14965924
TI  - Juvenility and maturation in conifers: current concepts.
AB  - Maturation in conifers includes several distinct and persistent changes in the
      growth habits of apical meristems. Despite many studies on maturation in
      conifers, there are still many aspects of the process that have not been
      elucidated. For example, it is not known why maturation of cotyledon-derived
      tissue culture plantlets is rapid, whereas the natural maturation process is
      gradual. Also, it is not known whether rejuvenation occurs as a result of mature
      cells reverting to the juvenile state, or whether rejuvenation results from
      selective multiplication of cells that have never matured. In this paper, I
      review the primary causes of maturation in woody plants, with emphasis on gene
      expression and its role in cell determination during the maturation process.
      Recent experiments demonstrating both accelerated maturation and apparent
      rejuvenation in several woody species are discussed with reference to several
      maturation models.

PMID- 14965925
TI  - Sexual expression in container-grown jack pine seedlings.
AB  - We assessed the effects of nitrogen, drought and gibberellin A(4/7) on sexual
      expression of 2- and 3-year-old jack pine (Pinus banksiana L.) seedlings grown in
      either a 1/3 peat/sand mix or a 3/1 peat/perlite mix. The seedlings were either
      watered daily (well-watered treatment) or droughted by withholding water from
      July 13 to August 24 (drought treatment). Half of the plants in each irrigation
      treatment were sprayed with 200 mg l(-1)gibberellin A(4/7) at weekly intervals
      from June 28 to August 24; the remaining plants were not sprayed. Each
      gibberellin treatment was split into three subplots, and each subplot was
      supplied with nitrogen in the nutrient solution at 3, 100 or 300 mg l(-1) from
      June 27 to September 11. The drought treatment increased pollen strobilus
      production, whereas seed strobilus production was higher in well-watered trees
      than in drought-treated trees in the first year after treatment, but not in the
      subsequent year. Gibberellin A(4/7) promoted seed strobilus production but not
      pollen strobilus production in the first year after treatment but had no effect
      in the second year. Among the nitrogen treatments, the largest proportion of
      trees bearing pollen strobili was in the 3 mg l(-1) N treatment. Nitrogen supply
      did not affect seed strobilus production in the first year after treatment, but
      in the following year, the proportion of trees with seed strobili was higher in
      the 3 mg l(-1) N treatment than in the 100 and 300 mg l(-1) N treatments. Growing
      medium had no detectable effect on pollen strobilus production, but in the year
      following treatment, more trees produced seed strobili in peat/sand than in
      peat/perlite.

PMID- 14965926
TI  - Nuclear and cytoplasmic changes associated with maturation in the vascular
      cambium of Larix laricina.
AB  - We studied the effects of apical maturation on the vascular cambium of juvenile
      and mature scions of Larix laricina (Du Roi) K. Koch that had been grafted on
      seedling rootstocks. Comparisons between the juvenile and mature cambium in
      nuclear genome size, nuclear shape, DNA concentration, number and volume of
      nucleoli per nucleus, and concentration of extranuclear RNAs, proteins and
      insoluble carbohydrates were conducted on four occasions during the annual cycle
      of cambial activity and dormancy. All investigated variables exhibited strong
      annual oscillations, whereas differences between the two maturation stages were
      less prominent. Many of the differences between the two phases could be explained
      by delayed spring reactivation and accelerated onset of dormancy in the mature
      cambium compared with the juvenile cambium. At the time of reactivation and
      during activity, the mature cambium exhibited lower genome size, lower DNA
      concentration, fewer nucleoli per nucleus and a higher extranuclear concentration
      of insoluble carbohydrates than the juvenile cambium. The dormant mature cambium
      contained more extranuclear RNAs than the dormant juvenile cambium. The observed
      differences provide circumstantial evidence of changes in chromatin organization
      or functioning, or both, during maturation.

PMID- 14965927
TI  - Transport and metabolism of gibberellins in relation to flower bud
      differentiation in Norway spruce (Picea abies).
AB  - A mixture of tritiated and deuterated gibberellin A(4) (GA(4)) was injected into
      the xylem of Norway spruce (Picea abies (L.) Karst) propagules, below an
      elongating shoot, or applied directly on the needles of an elongating shoot. The
      distribution of [(2)H(2)]GA(4) and [(3)H]GA(4) in the needles, stems and buds was
      determined after 4, 12 and 24 h. After 4 h, most of the xylem-injected GA(4) was
      found in the needles, whereas after 24 h, most of the GA(4) was found in the
      stem, with a small portion in the lateral buds. Of the GA(4) applied to the
      needles, 51% of the radioactivity recovered after 24 h was found in the stem and
      2% in the lateral buds. Mixtures of tritiated and deuterated GA(4) and GA(9) were
      injected into elongating shoots of one abundant-flowering family and one limited
      flowering family, grown either under conditions inductive for flowering (hot and
      dry, HD) or under noninductive conditions for flowering (cool and wet, CW).
      Shoots of both CW- and HD-treated propagules converted [(2)H(2)]GA(9) to
      [(2)H(2)]GA(51), [(2)H(2)]GA(4), [(2)H(2)]GA(34) and [(2)H(2)]GA(1), whereas
      [(2)H(2)]GA(4) was converted to [(2)H(2)]GA(34), [(2)H(2)]GA(1) and
      [(2)H(2)]GA(8). In shoots of both CW-treated clones, the main metabolite of
      [(3)H]GA(9) was in the GA(51) region. The HD-treated propagules converted more
      [(3)H]GA(9) to putative GA(4) than the CW-treated propagules. The main metabolite
      of [(3)H]GA(4) was in the GA(34) region. Radioactive metabolites were also found
      in the GA(1) and GA(8) regions.

PMID- 14965928
TI  - Effects of gibberellin A(4/7), root pruning and cytokinins on seed and pollen
      cone production in black spruce (Picea mariana).
AB  - Stem injections of 8-9-year-old black spruce (Picea mariana (Mill.) B.S.P.) trees
      with gibberellin A(4/7) (GA(4/7)) alone and in combination with root pruning
      increased both seed and pollen cone production in both 1991 and 1992. Combining
      GA(4/7) and root pruning produced a larger increase in reproductive bud
      production than either treatment alone, but the complementary effects were less
      during the warm dry summer in 1991 than during the wet summer in 1992. Cytokinin
      applications reduced the stimulatory effects of GA(4/7) and root pruning, and the
      degree of reduction varied with the amount and timing of application. Reduced
      reproductive bud production was attributed to cytokinin countering the effects of
      root pruning and natural drought on the GA(4/7) response.

PMID- 14965929
TI  - Flowering on long and short shoots of Larix laricina in response to differential
      timing of GA(4/7) applications.
AB  - In Larix, reproductive buds most often occur terminally on short shoots, but they
      can also differentiate in lateral positions on long shoots. The phenology of long
      and short shoots differs considerably, with short shoots breaking bud and
      expanding about 5 weeks before the start of long shoot extension. Foliar sprays
      of GA(4/7) were applied to 160 branches on 10 greenhouse-grown Larix laricina (Du
      Roi) K. Koch grafts either before (early) of after (late) the start of long shoot
      extension, or during both periods, to test whether the timing of GA(4/7)
      application affects flowering on short and long shoots. All three treatments
      induced flowering on both long and short shoots. The early GA(4/7) treatment led
      to slightly, but not significantly, more flowering on short shoots than on long
      shoots, whereas the late GA(4/7) treatment resulted in increased flowering on
      both types of shoots, but primarily on long shoots. Application of GA(4/7) during
      both periods did not result in increased flowering over the early or late
      treatment alone. Based on the fact that gibberellins are metabolized rapidly in
      conifers and our finding that GA(4/7) applied before shoot elongation, when the
      bud primordia were at a very early stage of development (detectable bud
      differentiation only occurred several weeks later), induced flowering on long
      shoots, we conclude that the early GA(4/7) treatment did not affect
      differentiation as it was occurring, but somehow predisposed the bud primordia to
      differentiate reproductively.

PMID- 14965930
TI  - Influences of crown size and maturation on flower production and sex expression
      in Picea glauca treated with gibberellin A(4/7).
AB  - We evaluated the effects of exogenous gibberellin A(4/7) (GA(4/7)) on the
      production of seed and pollen cones in four stock types of Picea glauca (Moench)
      Voss. From 1987 to 1991, a combined treatment that included GA(4/7), root pruning
      and heat stress was applied to 5- to 10-year-old container-grown grafts,
      representing over 90 clones and originating from 17- to 27-year-old ortets.
      Hormonal treatments were applied to pruned field-grown grafts in 1991 and 1992,
      and to unpruned field-grown grafts from the same set of clones in 1990, 1991 and
      1992. In 1992, 26-year-old mature trees in a progeny test were treated with
      GA(4/7). The GA(4/7) treatment was effective in promoting seed-cone production in
      all four stock types, whereas it promoted pollen-cone production only in unpruned
      field-grown grafts and mature trees. The older and taller a tree, the less the
      response to the GA(4/7) treatment was influenced by the climatic conditions
      prevailing during the differentiation phase.

PMID- 14965931
TI  - Constraints to seed production: temperate and tropical forest trees.
AB  - Reforestation requires a constant supply of high quality seed. Different methods
      have been used to measure seed and fruit production as a proportion of that which
      potentially could be produced. These estimates coupled with developmental studies
      permit determination of when and to what extent different biological constraints
      reduce seed and fruit production. These vary among species, years and sites.
      Overcoming biological constraints may be possible in seed orchards and seed
      production areas. Biological constraints include: (1) periodic or inadequate
      floral initiation, (2) asynchronous development and flowering, (3) floral
      abortion, (4) ovule abortion, (5) embryo abortion, and (6) failure of seeds and
      fruits to mature and our inability to determine maturity. Solutions to these
      constraints are varied but all must begin with an understanding of reproductive
      biology of each species.

PMID- 14965932
TI  - Abscisic acid and zygotic embryogenesis in Pinus taeda.
AB  - Indirect ELISA was used to quantify (+)-abscisic acid (ABA) in developing zygotic
      embryo and megagametophyte tissues from two loblolly pine (Pinus taeda L.) mother
      trees. On a dry weight basis, embryonic and megagametophytic ABA concentrations
      were highest during early development and decreased steadily to their lowest
      values at cone ripening. Embryonic ABA concentration was significantly higher
      than megagametophytic ABA concentration. The ABA content of embryos was lowest
      during early to mid-development; it increased rapidly during mid-development,
      subsequently declined, and then either remained constant or declined at cone
      ripening (late development). Total ABA per embryo increased rapidly just before
      the rapid increase in embryo dry weight. Total ABA per megagametophyte remained
      constant throughout development, except during mid-development when it
      temporarily declined.

PMID- 14965933
TI  - The role of acrotony in reproductive development in Picea.
AB  - The expression of acrotony (i.e., the increasing size of comparable lateral
      shoots toward the apex of the main shoot) was similar among first-order shoots
      borne along previous-year leaders of young Picea glauca (Moench) Voss, Picea
      mariana (Mill.) B.S.P. and Picea rubens Sarg. trees. The position and nature
      (i.e., whether cones, second-order shoots or non-flushed buds) of lateral axes
      borne along the first-order shoots were investigated. Seed cones occurred in
      proximal to distal positions, but not in terminal positions, on upper shoots, in
      medial to terminal positions on middle shoots, and in distal to terminal
      positions on lower shoots. Most non-flushed buds occurred in proximal positions
      on middle and lower shoots. In P. rubens, rate, duration and amount of elongation
      of first-order shoots increased acropetally. Thus lower shoots stopped elongating
      before upper shoots. Evidence of bud differentiation in P. rubens, as indicated
      by the presence of initiating leaf primordia, was seen first in sections of
      terminal buds of upper shoots. Differentiation of buds then proceeded basipetally
      along shoots and among shoots down the crown. Differentiation of buds in
      positions where cones are commonly borne became evident soon after shoot
      elongation was completed.

PMID- 14965934
TI  - Phenological measurements of microsporogenesis in trees.
AB  - The value of two heat sum methods, one linear (degree days > 5 degrees C) and the
      other curvilinear (period units), were assessed together with calendar days as
      predictors of the duration of microsporogenesis in seven natural stands of Norway
      spruce (Picea abies (L.) Karst.) and eleven natural stands of Scots pine (Pinus
      sylvestris L.). Microsporogenesis was divided into two subperiods: March 19 to
      tetrads (i.e., the end of meiosis) and tetrads to anthesis. The total period from
      March 19 to anthesis was also assessed. The methods were compared on a calendar
      day basis. When annual deviations between the predicted (stand means) and the
      observed annual heat sums were converted to days, the period unit method
      outperformed the other methods for both subphases and for the total period of
      microsporogenesis. The degree day parameter was more variable but a better
      predictor of the duration of the initial phase up to tetrads and of the total
      period than the calendar day parameter, but the calendar day parameter more
      accurately predicted the duration of the subphase from tetrads to anthesis. The
      heat sum methods were better predictors of the duration of development of
      microsporogenesis in exceptionally cold or warm years than the calendar day
      method.

PMID- 14965935
TI  - Pollen management for intensive seed orchard production.
AB  - Artificially increasing pollen supply (supplemental mass pollination (SMP)) to
      conifer seed orchards has the potential to increase seed yields and improve the
      genetic worth of seed crops that would otherwise suffer from the detrimental
      effects of pollen contamination and unbalanced paternal contribution. However,
      success rates, measured as the proportion of seed fertilized by SMP, have been
      low. This review examines the concepts underlying SMP and presents data for two
      SMP field trials with Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) and
      white/Engelmann spruce (Picea glauca (Moench) Voss, Picea engelmannii Parry ex
      Engelm.). The trial results are discussed with respect to pollen fertility,
      pollination technique, and competing pollen cloud density. I also summarize
      methods for ensuring the successful handling of pollen ex situ.

PMID- 14965936
TI  - Viability and seasonal distribution patterns of Scots pine pollen in Finland.
AB  - Germination ability and airborne counts of Scots pine (Pinus sylvestris L.)
      pollen were studied during the spring of 1993 at Turku in southern Finland (60
      degrees 32' N, 22 degrees 28' E) and at Utsjoki in northern Finland (69 degrees
      45' N, 27 degrees 01' E). Pollen waas trapped from the beginning of May to the
      end of June in a high-volume air sampler. Germination tests were performed to
      determine the in vitro pollen viability of the trapped pollen. Airborne pine
      pollen counts were obtained from a continuously operating Burkard trap located
      near each high-volume sampler. When male flowering began, phenological
      observations were carried out on pollen grains collected in rotored samplers
      located in pine and spruce stands and open fields near Turku and Utsjoki. In
      southern Finland, the peak period of pine pollen production was short, lasting
      for only 3 days, but it accounted for about 80% of the total germinating pine
      pollen yield for the year. The peak count was on May 20, with over 2000
      germinating pollen grains per cubic meter of air. Pollen germination rates of up
      to 70% were obtained during the week preceding the local pollen peak, and rates
      reached almost 90% on the peak day. Pollen viability remained at 45 to 65% for 1
      week after the peak. There was no significant difference between the pollen
      counts for day and night, indicating that during the main pollen season, the
      pollen source was close to Turku. Before the local pollen peak, the counts of
      living pine pollen were low, indicating that pine pollen transported over long
      distances was of little ecological importance in 1993 in the Turku area. In
      northern Finland, the first pollen grains were caught on July 4, and the peak day
      was July 13. However, no viable pollen was observed during this period,
      indicating that there was little gene drift from southern to northern Finland in
      1993.

PMID- 14965937
TI  - Effects of supplemental mass pollination (SMP) in a young and a mature seed
      orchard of Pinus sylvestris.
AB  - The effects of supplemental mass pollination (SMP) were studied in two Pinus
      sylvestris seed orchards differing in pollen production. Pollen was dusted over
      the whole tree during the period of peak female receptivity using a pressurized
      backpack sprayer. The success of SMP was assessed by means of allozyme markers.
      In the orchard with high pollen production, detectable differences in SMP success
      rate were found between clones, but the success rate was not influenced by the
      number of pollinations per day. The average estimated success rate of SMP was
      19%. In the orchard with low pollen production, no significant differences in SMP
      success rate were found between years (22 versus 34%) or between clones. The SMP
      success rate in the low pollen production orchard varied between 14 and 69%.

PMID- 14965938
TI  - Seed orchards in development.
AB  - This paper reviews the role of seed orchards as output systems for genetic
      improvement programs. In this paper, technological changes since the 1950s are
      examined, with emphasis on recent developments. The need to equate the type of
      seed orchard to the type of forestry practiced is recognized, as is the
      significance of the relationship between seed orchards and other output systems
      for genetically improved material.

PMID- 14965939
TI  - Surrogate pollen induction shortens the breeding cycle in loblolly pine.
AB  - Surrogate pollen induction (SPI) was evaluated on loblolly pine (Pinus taeda L.)
      donor scions from 5-year-old progeny that were grafted by topworking into the
      lower crowns of 16-year-old loblolly pine receptor clones in a seed orchard. On
      each of 25 study trees, one of three pollen induction treatments (wire girdle,
      saw girdle or control) was applied to 10 receptor branches below the graft
      location. Graft survival was 76%. Of the surviving grafts, 57% produced pollen
      strobili in March 1993, 13 months after grafting. The pollen induction treatments
      did not decrease graft survival or increase pollen production. Graft survival did
      not vary significantly among the donor scion genotypes, but the percentage of
      grafts with pollen was significantly related to the donor scion genotype. The
      mean number of pollen clusters induced per ramet also differed significantly
      among the donor scions. There was a tendency for pollen phenology of the grafted
      scions to be modified by the receptor clone. We conclude that surrogate pollen
      induction, coupled with accelerated female flower stimulation, can reduce the
      breeding schedule in loblolly pine to 3 years.

PMID- 14965940
TI  - Genetic and environmental variation of foliar nutrient concentrations and
      strobilus initiation in fertilized loblolly pine seed orchard ramets.
AB  - Fertilizer was applied annually for eight years to individual ramets in a
      loblolly pine (Pinus taeda L.) seed orchard at rates ranging from 0 to 448 kg
      nitrogen (N) ha(-1) year(-1). Clonal effects accounted for a major source of
      variation in both flowering and foliar nutrient concentrations. Foliar N
      concentrations were generally correlated with the intensity of fertilizer
      application, but were only weakly correlated with flowering. There was a long
      term trend for increasing concentrations of foliar manganese (Mn) and boron (B),
      and decreasing concentrations of magnesium (Mg) and zinc (Zn) with increasing
      fertilizer rates, although only the differences in Mn concentration were
      statistically significant. Fertilizer had little effect on the concentrations of
      other foliar macro- or micronutrients during the study. The optimum fertilizer
      rate for flowering was 224 kg N ha(-1) year(-1).

PMID- 14965941
TI  - Evaluation of the tree-improvement delivery system: factors affecting genetic
      potential.
AB  - Possible causes of the genetic erosion that occurs during the fragmented phases
      of the tree-improvement delivery system are reviewed. The impacts of intentional
      and unintentional directional selection during phenotypic selection, seed
      production (with its associated reproductive-phenology asynchrony, fecundity
      differential and varying propensity to inbreeding), seed processing and storage,
      and seedling production are evaluated. In general, genetic diversity and
      heterozygosity parameters of seed orchards are higher or similar to those
      observed in their natural-population counterparts. However, parental contribution
      to the resultant seed orchard seed crops is consistently asymmetrical, and this
      is a major cause of genetic erosion. In most cases, less than 20% of an orchard's
      clones contribute 80% of the cone crop, thus reducing the effective population
      size. Because seed germination of coniferous tree species is under strong
      maternal genetic control, the combined effects of differences in reproductive
      output and germination, as well as of management practices (e.g., simulated long
      term storage of seed showed that loss of viability during storage is genotype
      specific), cause unintentional directional selection during seedling production.
      This review confirms the need for genetic monitoring of each phase of the tree
      improvement delivery system, so that practical solutions can be developed to
      alleviate genetic erosion.

PMID- 14965942
TI  - Sexual reproduction in a greenhouse and reduced autumn frost hardiness of Picea
      abies progenies.
AB  - In 1989, identical crosses (2-3 females within males) were performed with Picea
      abies (L.) Karst. in a greenhouse seed orchard at Biri nursery and in an outdoor
      seed orchard at Huse, 32 km north of Biri. Pollination began 17 days earlier in
      the greenhouse than outdoors at Huse. The potted grafts in the greenhouse were
      moved outdoors when the seed cones were no longer receptive. Twelve full-sib
      family pairs (Biri and Huse) from these crosses were grown in a phytotron and
      tested for height and autumn frost hardiness during their first growing season.
      No significant difference was found between the indoor (Biri) and outdoor (Huse)
      progenies for height growth. However, the progenies from the greenhouse seed
      orchard were significantly more susceptible to frost than their full-sibs from
      the outdoor seed orchard. There was no significant interaction between males and
      the flowering environment, but a significant female x flowering environment
      interaction was present as a result of greater differences in frost hardiness
      between progenies from females in the greenhouse seed orchard than in the outdoor
      seed orchard. Although seeds from the outdoor seed orchard generally had a
      greater biomass than seeds from the greenhouse seed orchard, the difference in
      seed weight did not explain the difference in frost hardiness. We hypothesize
      that temperature and photoperiod during pollination and fertilization affect the
      frost hardiness of the progenies.

PMID- 14965943
TI  - Responses of foliar gas exchange to long-term elevated CO(2) concentrations in
      mature loblolly pine trees.
AB  - Branches of field-grown mature loblolly pine (Pinus taeda L.) trees were exposed
      for 2 years (1992 and 1993) to ambient or elevated CO(2) concentrations (ambient
      + 165 micro mol mol(-1) or ambient + 330 micro mol mol(-1) CO(2)). Exposure to
      elevated CO(2) concentrations enhanced rates of net photosynthesis (P(n)) by 53
      111% compared to P(n) of foliage exposed to ambient CO(2). At the same CO(2)
      measurement concentration, the ratio of intercellular to atmospheric CO(2)
      concentration (C(i)/C(a)) and stomatal conductance to water vapor did not differ
      among foliage grown in an ambient or enriched CO(2) concentration. Analysis of
      the relationship between P(n) and C(i) indicated no significant change in
      carboxylation efficiency of ribulose-1,5-bisphosphate carboxylase/oxygenase
      during growth in elevated CO(2) concentrations. Based on estimates derived from
      P(n)/C(i) curves, there were no apparent treatment differences in dark
      respiration, CO(2) compensation point or P(n) at the mean C(i). In 1992, foliage
      in the three CO(2) treatments yielded similar estimates of CO(2)-saturated P(n)
      (P(max)), whereas in 1993, estimates of P(max) were higher for branches grown in
      elevated CO(2) than in ambient CO(2). We conclude that field-grown loblolly pine
      trees do not exhibit downward acclimation of leaf-level photosynthesis in their
      long-term response to elevated CO(2) concentrations.

PMID- 14965944
TI  - Gas exchange, leaf structure and nitrogen in contrasting successional tree
      species growing in open and understory sites during a drought.
AB  - Seasonal ecophysiology, leaf structure and nitrogen were measured in saplings of
      early (Populus grandidentata Michx. and Prunus serotina J.F. Ehrh.), middle
      (Fraxinus americana L. and Carya tomentosa Nutt.) and late (Acer rubrum L. and
      Cornus florida L.) successional tree species during severe drought on adjacent
      open and understory sites in central Pennsylvania, USA. Area-based net
      photosynthesis (A) and leaf conductance to water vapor diffusion (g(wv)) varied
      by site and species and were highest in open growing plants and early
      successional species at both the open and understory sites. In response to the
      period of maximum drought, both sunfleck and sun leaves of the early successional
      species exhibited smaller decreases in A than leaves of the other species. Shaded
      understory leaves of all species were more susceptible to drought than sun leaves
      and had negative midday A values during the middle and later growing season.
      Shaded understory leaves also displayed a reduced photosynthetic light response
      during the peak drought period. Sun leaves were thicker and had a greater mass
      per area (LMA) and nitrogen (N) content than shaded leaves, and early and middle
      successional species had higher N contents and concentrations than late
      successional species. In both sunfleck and sun leaves, seasonal A was positively
      related to predawn leaf Psi, g(wv), LMA and N, and was negatively related to
      vapor pressure deficit, midday leaf Psi and internal CO(2). Although a
      significant amount of plasticity occurred in all species for most gas exchange
      and leaf structural parameters, middle successional species exhibited the largest
      degree of phenotypic plasticity between open and understory plants.

PMID- 14965945
TI  - Frost resistance and susceptibility to ice formation during natural hardening in
      relation to leaf anatomy in three evergreen tree species from New Zealand.
AB  - Foliar frost resistance of three endemic New Zealand land trees, Nothofagus
      menziesii (Hook. f.) Oerst. (Fagaceae), Pittosporum eugenioides A. Cunn.
      (Pittosporaceae) and Griselinia littoralis Forst. f. (Cornaceae), was examined as
      the trees hardened from late summer to midwinter in a lowland forest site. The
      lowest temperatures causing 50% damage (LT(50)) occurred in late winter and were
      similar to those recorded for other forest trees native to New Zealand (-11.7
      degrees C in N. menziesii, -10.7 degrees C in P. eugenioides, and -10.6 degrees C
      in G. littoralis). All three species hardened by 4-7 degrees C, with G.
      littoralis showing the least frost resistance in summer and hence the greatest
      degree of hardening. Thermal analysis during freezing indicated that all three
      species became more tolerant of extracellular ice formation in winter.
      Measurements of chlorophyll a fluorescence correlated well with visible injury.
      The differing patterns of frost damage development in the three species were
      related to leaf anatomy: visible injury was localized within the small
      compartments formed by the highly septate leaves of the most resistant species,
      N. menziesii, and was somewhat localized in the partially septate leaves of P.
      eugenioides, whereas damage could be initiated anywhere in the aseptate leaves of
      G. littoralis,which was the least frost resistant species, particularly in
      summer.

PMID- 14965946
TI  - Offsetting effects of reduced root hydraulic conductivity and osmotic adjustment
      following drought.
AB  - Root hydraulic conductivity (L(p)) and leaf osmotic potential at full turgor
      (Psi(pi,o)) were measured in young, drought-stressed and nonstressed peach
      (Prunus persica (L.) Batsch), olive (Olea europaea L.), citrumelo (Poncirus
      trifoliata Raf. x Citrus paradisi Macf.) and pistachio (Pistachia integerrima
      L.). Drought stress caused a 2.5- to 4.2-fold reduction in L(p), depending on
      species, but Psi(pi,o) was reduced only in citrumelo and olive leaves by 0.34 and
      1.4 MPa, respectively. No differences existed in L(p) among species for
      nonstressed plants. A simple model linking L(p) to osmotic adjustment through
      leaf water potential (Psi) quantified the offsetting effects of reduced L(p) and
      osmotic adjustment on the hypothetical turgor pressure difference between drought
      stressed and nonstressed plants (DeltaPsi(p)). For olive, the 2.5-fold reduction
      in L(p) caused a linear decrease in DeltaPsi(p) such that the effect of osmotic
      adjustment was totally negated at Psi = -3.2 MPa. Thus, no stomatal closure would
      be required to maintain higher turgor in drought-stressed olive plants than in
      nonstressed plants over their typical diurnal range of Psi (-0.6 to -2.0 MPa).
      For citrumelo, osmotic adjustment was offset by reduced L(p) at Psi approximately
      -0.9 MPa. Unlike olive, stomatal closure would be necessary to maintain higher
      turgor in drought-stressed citrumelo plants than in nonstressed plants over their
      typical diurnal range of Psi (0 to -1.5 MPa). Regardless of species or the
      magnitude of osmotic adjustment, my analysis suggests that a drought-induced
      reduction in L(p) reduces or eliminates turgor maintenance through osmotic
      adjustment.

PMID- 14965947
TI  - Maintenance and growth respiration of the aboveground parts of young field-grown
      hinoki cypress (Chamaecyparis obtusa).
AB  - Aboveground respiration of five 8-year-old trees of field-grown hinoki cypress
      (Chamaecyparis obtusa (Sieb. et Zucc.) Endl.) was nondestructively measured at
      monthly intervals over 1 year with an enclosed standing tree method. The
      relationship between monthly specific respiration rate and monthly mean relative
      growth rate at the individual tree level was described by a linear equation.
      During the dormant season, respiration was used mainly for maintenance purposes,
      whereas during the growing season, more than 40% of the respiration was used for
      growth purposes, i.e., 60 to 70% in May. We conclude that annual maintenance and
      growth respiration of a tree are directly proportional to the aboveground
      phytomass and its annual increment, respectively. The maintenance coefficient was
      estimated to be 0.504 +/- 0.039 (SE) kg kg(-1) year(-1), indicating that the
      amount respired for maintaining already existing phytomass was equivalent to
      about half of the existing phytomass. The growth coefficient was estimated to be
      0.772 +/- 0.043 (SE) kg kg(-1), indicating that the amount respired for
      constructing new phytomass was equivalent to about three-fourths of the annual
      phytomass increment. The annual stand maintenance and growth respiration were,
      respectively, 8.8 Mg ha(-1) year(-1) for an aboveground biomass of 17.4 Mg ha(-1)
      and 5.0 Mg ha(-1) year(-1) for an annual stand aboveground biomass increment of
      6.5 Mg ha(-1) year(-1). About two-thirds of the total respiration was used to
      maintain already existing biomass, and about one-third was used to construct new
      biomass.

PMID- 14965948
TI  - Photosynthetic and transpirational responses of red spruce understory trees to
      light and temperature.
AB  - Understory red spruce (Picea rubens Sarg.) trees, between 20 and 50 cm in height
      and 12 years or more in age, were collected from mid- and high-elevation stands
      in north-central Vermont and placed in a closed-cuvette system to measure
      photosynthetic and transpirational responses to photosynthetic photon flux
      density (PPFD) and temperature. Photosynthesis, dark respiration, transpiration
      and water-use efficiency of trees from both stands responded to changes in PPFD
      and temperature in similar ways. Trees from both stands exhibited maximum rates
      of net photosynthesis at temperatures between 15 and 20 degrees C, and exposure
      to higher temperatures resulted in reduced rates of photosynthesis and increased
      rates of respiration. Net photosynthetic rates generally increased with
      increasing light intensity but began to level off at 250 micro mol m(-2) s(-1).
      Water-use efficiency was maximal when temperature and PPFD were at 15 degrees C
      and above 400 micro mol m(-2) s(-1), respectively.

PMID- 14965949
TI  - Temperature control of the development of frost hardiness in two populations of
      Leptospermum scoparium.
AB  - Seedlings of Leptospermum scoparium J.R. et G. Forst (manuka) originating from
      seed from a low altitude coastal site (Auckland) and from a high altitude inland
      site (Desert Road) were grown for 96 days in four controlled environments to
      compare the relationship between growth temperature and frost hardening.
      Day/night temperature treatments were 12/6, 12/3, 12/0 and 12/-3 degrees C. Frost
      hardiness was determined at 14-day intervals by exposing whole seedlings to
      temperatures ranging from -2 to -8 degrees C. Frost damage differed significantly
      between the two populations: Desert Road seedlings were less affected than
      Auckland seedlings. At all growth temperatures, the time courses of frost
      hardiness of both populations followed curvilinear relationships reaching a
      maximum hardiness at about Day 50, after which the seedlings spontaneously
      dehardened. The rate of frost hardening increased linearly with decreasing
      temperature from 6 to 0 degrees C, but thereafter, no further increase occurred
      with decreasing temperature to -3 degrees C. The frost hardening process was more
      sensitive to temperature in the Desert Road seedlings than in the Auckland
      seedlings, and this difference may account for the intraspecific variation in
      frost hardening capacity of this species. Comparisons with Pinus radiata D. Don
      and Lolium perenne L. indicated that interspecific variation in frost hardening
      capacity can also be accounted for by differences in the sensitivity of the
      hardening process to temperature.

PMID- 14965950
TI  - Water relations, gas exchange and growth of dominant and suppressed shoots of
      Arbutus unedo L.
AB  - Basal shoots produced by Arbutus unedo L. after cutting at ground level vary in
      size and growth rate, and are classified accordingly as dominant or suppressed.
      The suppressed shoots eventually cease growth and die. In this study, we
      investigated the role of light and water in the competition among shoots of A.
      unedo. Dominant and suppressed shoots of A. unedo showed similar leaf water
      potentials and tissue water relations over the year, suggesting that water status
      is not responsible for the lack of flushing in suppressed shoots. Although
      suppressed shoots did not flush under low light, they showed many characteristics
      of shade-tolerant plants. Leaves of suppressed shoots had lower leaf conductance
      and light-saturated photosynthetic rate, and higher specific leaf area than
      leaves of dominant shoots. We conclude that light was the main resource
      determining competition among shoots and the death of suppressed shoots.

PMID- 14965951
TI  - Influence of copper on root growth and morphology of Pinus pinea L. and Pinus
      pinaster Ait. seedlings.
AB  - We assessed the effects of Cu on root growth and morphology of stone pine (Pinus
      pinea L.) and maritime pine (Pinus pinaster Ait.) seedlings grown in culture
      solutions supplied with 0.012 (control), 0.1, 1 or 5 micro M CuSO(4). The
      presence of 5 micro M Cu in the nutrient solution completely inhibited root
      growth of both species within 3 days. In both species, taproot elongation was
      reduced in the presence of 1 micro M Cu, although partial growth recovery
      occurred after 7 days of treatment. The presence of 0.1 micro M Cu in the culture
      solution slightly enhanced root elongation in P. pinaster, but did not
      significantly influence root elongation in P. pinea. In both species, root weight
      per unit length increased in response to Cu exposure, and in P. pinaster, root
      diameter was significantly increased. The Cu treatments also affected lateral
      root number and length. In the presence of 1 micro M Cu, both species formed only
      short lateral primordia. The 1 micro M Cu treatment increased the lateral root
      index (number of roots per cm of root length) of P. pinaster, but decreased that
      of P. pinea, compared with control values. Neither the 0.1 nor 1 micro M Cu
      treatment had a significant effect on the mitotic index of either species. We
      conclude that cell elongation is more sensitive to Cu than cell division. Cell
      membrane damage, as indicated by Trypan blue staining, occurred after 10 days of
      exposure to 1 micro M Cu.

PMID- 14965952
TI  - Arbuscular mycorrhizal induced changes to plant growth and root system morphology
      in Prunus cerasifera.
AB  - We compared root system morphogenesis of micropropogated transplants of Prunus
      cerasifera L. inoculated with either of the arbuscular mycorrhizal (AM) fungi
      Glomus mosseae or Glomus intraradices or with the ericoid mycorrhizal species
      Hymenoscyphus ericae. All plants were grown in sand culture, irrigated with a
      nutrient solution that included a soluble source of phosphorus, for 75 days after
      transplanting. Arbuscular mycorrhizal colonization increased both the survival
      and growth (by over 100%) of transplants compared with either uninoculated
      controls or transplants inoculated with H. ericae. Arbuscular mycorrhizal
      colonization increased root, stem and leaf weights, leaf area, root length and
      specific leaf area, and it decreased root length/leaf area ratio, root/shoot
      weight ratio and specific root length. Both uptake of phosphorus and its
      concentration in leaves were increased by AM infection, although the time course
      of the relationships between intensity of AM infection and P nutrition were
      complex and suggested a role for factors other than nutrition. The time course
      for the development of infection varied. It was most rapid with G. mosseae, but
      it was ultimately higher with G. intraradices. None of the treatments
      significantly affected the lengths of adventitious roots or the first-, second-
      or third-order laterals that developed from them. Arbuscular mycorrhizal
      colonization increased the intensity of branching in all root orders with the
      effect being most obvious on first-order lateral roots where the number of
      branches increased from under 100 to over 300 brances m(-1). As a result,
      although first-order laterals made up 55% of the root systems of control plants,
      the comparable value was 36% in AM-infected plants. In contrast, second-order
      laterals represented 25% of control root systems, but 50% of AM-colonized root
      systems. Glomus intraradices but not G. mosseae increased root diameter.
      Anatomical studies revealed no changes in the overall form of the root tip,
      although there were changes in the diameter of the root cap, cell numbers and
      cell size. Hymenoscyphus ericae increased the duration of the metaphase index.
      Both AM fungal treatments increased the concentrations of soluble proteins in
      root extracts and modified the protein profiles by the elimination and addition
      of protein bands detected by PAGE analysis. We conclude that AM fungal
      inoculation influenced processes in the root system at different levels, but not
      all effects were due to improved P nutrition or increased physiological age.

PMID- 14965953
TI  - Effects of thinning on soil and tree water relations, transpiration and growth in
      an oak forest (Quercus petraea (Matt.) Liebl.).
AB  - To quantify the effects of crown thinning on the water balance and growth of the
      stand and to analyze the ecophysiological modifications induced by canopy opening
      on individual tree water relations, we conducted a thinning experiment in a 43
      year-old Quercus petraea stand by removing trees from the upper canopy level.
      Soil water content, rainfall interception, sap flow, leaf water potential and
      stomatal conductance were monitored for two seasons following thinning. Seasonal
      time courses of leaf area index (LAI) and girth increment were also measured.
      Predawn leaf water potential was significantly higher in trees in the thinned
      stand than in the closed stand, as a consequence of higher relative extractable
      water in the soil. The improvement in water availability in the thinned stand
      resulted from decreases in both interception and transpiration. From Year 1 to
      Year 2, an increase in transpiration was observed in the thinned stand without
      any modification in LAI, whereas changes in transpiration in the closed stand
      were accompanied by variations in LAI. The different behaviors of the closed and
      open canopies were interpreted in terms of coupling to the atmosphere. Thinning
      increased inter-tree variability in sap flow density, which was closely related
      to a leaf area competition index. Stomatal conductance varied little inside the
      crown and differences in stomatal conductance between the treatments appeared
      only during a water shortage and affected mainly the closed stand. Thinning
      enhanced tree growth as a result of a longer growing period due to the absence of
      summer drought and higher rates of growth. Suppressed and dominant trees
      benefited more from thinning than trees in the codominant classes.

PMID- 14965954
TI  - Effects of light availability and tree size on the architecture of assimilative
      surface in the canopy of Picea abies: variation in needle morphology.
AB  - Needle dimensions, needle surface area, needle dry weight per area (LWA) and
      needle density (ND, needle weight per volume) were measured in terminal current
      year shoots in a natural canopy of variably sized Picea abies (L.) Karst. trees
      growing along a light gradient. Needle shape was described as a rhomboid. Needle
      width (D(2)) increased with increasing diffuse site factor, a(d) (relative amount
      of penetrating diffuse solar radiation), whereas needle thickness (D(1)) remained
      nearly constant, resulting in an inverse relationship between D(1)/D(2) and a(d)
      and an increase in the ratio of total (TLA) to projected needle surface area
      (PLA) with increasing a(d). Because of the variations in needle morphology with
      respect to light availability, the shoot parameters used in present canopy models
      are also expected to be light-sensitive, and studies involving shoot morphology
      should also consider the variability in needle geometry. Needle dimensions and
      total tree height were not correlated. However, LWA increase with both increasing
      a(d) and total tree height. When LWA was expressed as the product of ND and
      needle height (NH, height of the rhomboidal transverse section of a needle), LWA
      appeared to increase with irradiance, because of changing NH, and with total tree
      height, because of changing needle density.

PMID- 14965955
TI  - Belowground carbon allocation in unfertilized and fertilized red pine plantations
      in northern Wisconsin.
AB  - We estimated carbon allocation to belowground processes in unfertilized and
      fertilized red pine (Pinus resinosa Ait.) plantations in northern Wisconsin to
      determine how soil fertility affects belowground allocation patterns. We used
      soil CO(2) efflux and litterfall measurements to estimate total belowground
      carbon allocation (root production and root respiration) by the carbon balance
      method, established root-free trenched plots to examine treatment effects on
      microbial respiration, estimated fine root production by sequential coring, and
      developed allometric equations to estimate coarse root production. Fine root
      production ranged from 150 to 284 g m(-2) year(-1) and was significantly lower
      for fertilized plots than for unfertilized plots. Coarse root production ranged
      from 60 to 90 g m(-2) year(-1) and was significantly lower for fertilized plots
      than for unfertilized plots. Annual soil CO(2) fluxes ranged from 331 to 541 g C
      m(-2) year(-1) and were significantly lower for fertilized plots than for
      unfertilized plots. Annual foliage litterfall ranged from 110 to 187 g C m(-2)
      year(-1) and was significantly greater for fertilized plots than for unfertilized
      plots. Total belowground carbon allocation ranged from 188 to 395 g C m(-2) year(
      1) and was significantly lower for fertilized than for unfertilized plots. Annual
      soil CO(2) flux was lower for trenched plots than for untrenched plots but did
      not differ between fertilized and unfertilized trenched plots. Collectively,
      these independent estimates suggest that fertilization decreased the relative
      allocation of carbon belowground.

PMID- 14965956
TI  - Isotopic carbon discrimination and leaf nitrogen content of Erica arborea L.
      along a CO(2) concentration gradient in a CO(2) spring in Italy.
AB  - We studied a Mediterranean species (Erica arborea L.) growing in a CO(2) spring
      in Italy that was naturally exposed for generations to a gradient of atmospheric
      CO(2) concentrations. The CO(2) concentration gradient to which different
      individual plants were exposed was determined by an indirect method based on
      radioisotope analysis. The stable carbon isotope ratio of sampled leaves was
      determined by mass spectrometry, and isotopic discrimination was then calculated.
      Leaf nitrogen, specific leaf area, total soil nitrogen, soil organic matter
      content and soil pH were also measured. In one group of plants, grown on a
      homogeneous soil and exposed to moderate CO(2) enrichment, isotopic
      discrimination was significantly reduced in response to increasing CO(2)
      concentrations, whereas the intercellular CO(2) concentration and leaf nitrogen
      content were almost unaffected. In a second group of plants, grown along a
      gradient of CO(2) concentration and soil nitrogen content, leaf nitrogen content
      was reduced when nitrogen availability was limiting. However, when soil nitrogen
      was available in excess, even very high CO(2) concentrations did not result in
      increased discrimination or reduced leaf nitrogen content in the long term. The
      results are discussed with respect to current theories about the long-term CO(2)
      response of plants based on several years of experimentation with elevated
      atmospheric CO(2) concentrations under controlled conditions.

PMID- 14965957
TI  - Growth and carbohydrate status of coppice shoots of hybrid poplar following shoot
      pruning.
AB  - Fifteen, 1-year-old Populus maximowiczii Henry x P. nigra L. 'MN9' trees were
      decapitated and allowed to sprout. After 8 weeks, all had 6 to 10 coppice shoots.
      All shoots, except the tallest (dominant) shoot, were removed from five of the
      trees (pruned treatment), and shoot growth, gas exchange and carbohydrate status
      were compared in the pruned and unpruned trees. Although photosynthetic rate of
      recently mature leaves of pruned trees was approximately 50% greater than that of
      leaves on the dominant shoot of unpruned trees, and the dry weight of leaves of
      pruned trees was 37% greater than that of the leaves on the dominant shoot of
      unpruned trees, the shoot dry matter relative growth rate did not differ between
      treatments. Concentrations of water-soluble carbohydrates and starch in the
      uppper stem and leaves of the dominant shoot were similar in pruned and unpruned
      trees. However, relative to that of the dominant shoot in unpruned trees, the
      lower stem in pruned trees was depleted in both soluble carbohydrates and starch.
      Starch deposition, assessed as the quantity of (14)C-starch in tissues 24 h after
      a fully expanded source leaf was labeled with (14)CO(2), was 3.9 times greater in
      roots of pruned trees than in roots of unpruned trees. We conclude that early
      removal of all but the dominant shoot reduces the carbohydrate status of the
      roots and the lower portion of the stem by eliminating the excised shoots as a
      source of photosynthate.

PMID- 14965958
TI  - Allocation of mass in trees subject to nitrogen and magnesium limitation.
AB  - It has previously been shown that lack of magnesium, potassium or manganese
      depresses allocation of new mass to roots in trees, and that these elements often
      occur in low amounts in declining forest stands. A model for tree growth and
      nutrient uptake was used to examine the effect of allocation pattern of new plant
      mass on growth and development in soils with low nutrient concentrations. Growth
      parameters and empirical allocation functions from steady-state experiments with
      birch (Betula pendula Roth.) and Norway spruce (Picea abies (L.) Karst.) limited
      by N or Mg were used in the simulations. The simulation results show that plant
      nutrient concentration is sensitive to decreases in soil Mg concentration and is
      not counteracted by an increased allocation of plant mass to roots. A 50%
      reduction in the optimal soil Mg concentration decreased the plant Mg
      concentration to the threshold of survival, whereas a 50% reduction of soil N had
      much less effect. Birch was more sensitive to low soil Mg concentration than
      Norway spruce. We conclude that, in the discussion of forest decline, it may be
      important to consider the decreased allocation of mass to roots when Mg (or K or
      Mn) is in short supply.

PMID- 14965959
TI  - Winter photosynthesis of red spruce from three Vermont seed sources.
AB  - We evaluated winter (January through March) carbon assimilation of red spruce
      (Picea rubens Sarg.) from three Vermont seed sources grown in a common garden in
      northwestern Vermont. Although CO(2) exchange rates were generally low, net
      photosynthetic rates increased during two prolonged thaws. Significant
      correlations between CO(2) exchange rates and multiday air temperature means
      supported our observations of enhanced gas exchange during extended periods of
      elevated temperature. Increases in photosynthesis during thaws occurred before
      observed increases in leaf conductance, indicating that initial changes in
      photosynthesis were probably not associated with changes in stomatal aperture.
      Results of correlations between photosynthetic rates and PAR suggested that solar
      irradiance did not have a strong effect on winter carbon capture. Rates of net
      photosynthesis differed among seed sources. Trees from the Mt. Mansfield source
      had the highest average rates of photosynthesis and, at times, rates for
      individual trees from this source approximated those occurring during the growing
      season. Because seed sources differed in photosynthetic rates but not in leaf
      conductance, we conclude that differences in winter photosynthesis among seed
      sources were primarily attributable to factors other than changes in stomatal
      aperture.

PMID- 14965960
TI  - Effects of needle age, long-term temperature and CO(2) treatments on the
      photosynthesis of Scots pine.
AB  - Naturally regenerated 20-25-year-old Scots pine (Pinus sylvestris L.) trees were
      grown in open-top chambers in the presence of an elevated temperature or CO(2)
      concentration, or both. The elevated temperature treatment was administered year
      round for 3 years. The CO(2) treatment was applied between April 15 and September
      15 for 2 years. The photosynthetic responses of 1- and 2-year-old needles to
      varying photon flux densities (0-1500 micro mol m(-2) s(-1)) and CO(2)
      concentrations (350, 700 and 1400 micro mol mol(-1)) during measurement were
      determined. The CO(2) treatment alone increased maximum photosynthetic rate and
      light-use efficiency, but decreased dark respiration rate, light compensation and
      light saturation regardless of needle age. In contrast, the temperature treatment
      decreased maximum photosynthetic rate and photosynthetic efficiency, but
      increased dark respiration rate, light compensation and light saturation. The
      aging of needles affected the photosynthetic performance of the shoots; values of
      all parameters except photosynthetic efficiency were less in 2- than in 1-year
      old needles. The CO(2) treatment decreased and the temperature treatment enhanced
      the reduction in maximum photosynthesis due to needle aging.

PMID- 14965961
TI  - Estimating stand transpiration in a Eucalyptus populnea woodland with the heat
      pulse method: measurement errors and sampling strategies.
AB  - Sap flow measurement techniques, such as the heat pulse (compensation) method,
      are practical means for estimating the water use of individual trees and are
      often the only reasonable alternative for measuring forest and woodland
      transpiration in complex heterogeneous terrain. The need to scale estimates of
      water use from a sample of individual stems to a stand (population) of known area
      may be satisfied by applying scalars of flux based on tree size or domain. We
      estimated the aggregate errors in applying the heat pulse technique to the
      estimation of stand transpiration in a poplar box (Eucalyptus populnea F.J.
      Muell.) woodland in southeastern Queensland, Australia, by a combination of
      precision analyses, experimental validation and Monte Carlo simulations of
      sampling errors. Errors in sap flux density measurements were approximately 13%.
      The potential error in the flux estimates for individual stems with stratified
      sampling of sap flux density with depth and bole quadrant based on four sensors
      was an additional 25%. Conducting wood area, diameter at 1.3 m, leaf area and
      domain based on Ecological Field Theory all proved excellent scalars of flux at
      the stand level. With a sample size of six trees stratified by diameter,
      coefficients of variation in scaling to the stand level were approximately 5% for
      any of these scalars. The greatest potential source of error in estimating stand
      transpiration by the heat pulse method was in the measurement of the fluxes of
      individual stems; scaling these measurements to a homogeneous stand of trees
      involved less uncertainty.

PMID- 14965962
TI  - Regulation of photosynthesis in interior spruce during water stress: changes in
      gas exchange and chlorophyll fluorescence.
AB  - Photosynthetic response to water stress was analyzed in 1-year-old interior
      spruce (Picea glauca (Moench) Voss x P. engelmanni Parry hybrid complex)
      seedlings and emblings produced from somatic embryogenesis. Carbon dioxide
      uptake, oxygen evolution and chlorophyll fluorescence at 20 degrees C were
      monitored as predawn shoot water potential (Psi) decreased. Concurrently with
      stomatal closure, carbon assimilation declined rapidly as Psi decreased to -1.0
      MPa. Oxygen evolution at 10,000 micro l CO(2) l(-1) declined continuously as Psi
      decreased to -1.6 MPa. At photon flux densities (PFD) above 50 micro mol m(-2) s(
      1), photochemical efficiency of photosystem (PS) II observed during actinic light
      exposure (Phi(II), calculated as DeltaF/F(m)') decreased as Psi decreased. At the
      same PFDs, photochemical quenching (q(P)) declined with decreasing Psi and
      nonphotochemical quenching (q(N)) increased steadily. At PFDs below 50 micro mol
      m(-2) s(-1), major decreases in q(N) were not observed until Psi decreased below 
      1.6 MPa. We identified three phases of photosynthetic response to progressive
      water stress in interior spruce: a pronounced decline in gas exchange, subsequent
      photoprotective changes in chlorophyll fluorescence as primary photochemistry was
      down-regulated, and a decline in photochemical efficiency of dark-adapted
      needles.

PMID- 14965963
TI  - Evaluation of sampling schemes for estimating instantaneous whole-tree
      photosynthesis in Populus clones: a modeling approach.
AB  - We evaluated several sampling schemes for estimating instantaneous whole-tree
      photosynthesis of 1-year-old Populus clones. Growth of two clones was simulated
      under varying weather conditions and leaf orientation scenarios providing
      photosynthetic data on a leaf-by-leaf basis throughout the growing season. Simple
      random sampling, stratified random sampling and a series of physiologically based
      sampling schemes were evaluated using either whole-leaf photosynthesis or
      photosynthetic rate (i.e., photosynthesis per unit leaf area) as the sampling
      attribute. Ratio and regression estimators with leaf area as an auxiliary
      variable were also studied. On the basis of their bias and accuracy in estimating
      instantaneous whole-tree photosynthesis (mg CO(2)), the physiologically based
      sampling schemes were superior for all combinations of clone type, weather
      condition and leaf orientation. Aspects of extending the sampling process to
      estimate daily and seasonal photosynthesis are also elaborated.

PMID- 14965964
TI  - Dynamic response of stomata to changing irradiance in loblolly pine (Pinus taeda
      L.).
AB  - Dynamic changes in stomatal conductance and the rate of photosynthesis were
      measured as periods of shading (decrease in irradiance from 800 to 200 micro mol
      m(-2) s(-1)) between 5 and 60 min were imposed on needles of Pinus taeda L. trees
      under laboratory conditions. Shading induced a 39% decrease in stomatal
      conductance but the rate of change was slow. Average time constants (+/- standard
      error) were shorter for the decrease in stomatal conductance when shading was
      imposed for 30 min (14.8 +/- 1.3 min) than for the increase in stomatal
      conductance when shading was removed (25.5 +/- 3.4 min). The time constants for
      increasing stomatal conductance when shading was removed were linearly related to
      the length of the previous dark period. The rate of photosynthesis fell
      immediately by 58% when shading was imposed and increased more rapidly than the
      change in stomatal conductance when shading was removed. The increase in
      photosynthesis during the induction phase after shading was removed was limited
      by both stomatal and biochemical effects. The long time constants for stomatal
      response contributed to the poor correlations between stomatal conductance and
      instantaneous measurements of irradiance from field data. However, the slow
      response of stomatal conductance to changes in irradiance had little effect on
      total daily transpiration, carbon gain and water-use efficiency.

PMID- 14965965
TI  - Environmental control of ozone uptake in Larix decidua Mill.: a comparison
      between different altitudes.
AB  - We studied ozone (O(3)) uptake by European larch (Larix decidua Mill.) needles
      under ambient conditions at both a low and a high elevation site. At a given
      ambient O(3) concentration, the rate of O(3) uptake by needles was effectively
      controlled by stomatal conductance and, hence, by factors such as light, humidity
      and water status, which control stomatal conductance. At both study sites,
      atmospheric water vapor pressure deficit (VPD) was the climatic factor most
      closely correlated with ambient O(3) concentration. Thus, when ambient O(3)
      concentrations were highest, O(3) flux into the needles tended to be restricted
      by narrowing of the stomata. Mitigation of potential O(3) stress by stomatal
      closure was most marked at the low elevation site where both soil water stress
      and atmospheric VPD were greater than at the high elevation site.

PMID- 14965966
TI  - Rapid freezing induces winter injury symptomatology in red spruce foliage.
AB  - Red spruce (Picea rubens Sarg.) suffers frequent and extensive injury to current
      year foliage during the winter. Experimental freezing of red spruce foliage at
      cooling rates > 10 degrees C min(-1) induced visible symptomatology similar to
      natural winter injury at the branch, needle and cellular levels. Such damage was
      associated with a low-temperature exotherm near -10 to -12 degrees C, a loss in
      needle fluorescence, massive cellular disruption, foliar discoloration, and low
      needle survival. Susceptibility of individual trees to rapid freezing injury was
      associated with historical winter injury patterns and alterations in foliar
      nutrition. We conclude that anthropogenic deposition may alter the sensitivity of
      trees to winter injury caused by rapid temperature changes.

PMID- 14965967
TI  - Effects of cold storage and water stress on water relations and gas exchange of
      white spruce (Picea glauca) seedlings.
AB  - To determine the effects of lifting time and storage on water-stress resistance
      of nursery-grown white spruce (Picea glauca (Moench) Voss) seedlings, we compared
      gas exchange, water relations and mortality of 3-year-old seedlings lifted in
      October 1991 and stored at -2 degrees C for 3 months with seedlings lifted in
      January 1992. The seedlings were placed in nutrient solution and subjected to 
      1.1 or -2.7 MPa water stress induced by polyethylene glycol 3350 for 9 days.
      Water stress, but not lifting time, had a significant effect on seedling net
      assimilation, symplastic volume and turgor loss point. In a second experiment,
      seedlings lifted in October 1991 were stored at -2 degrees C for 7 months and
      compared with seedlings lifted in May 1992. The seedlings were planted in pots,
      and their gas exchange and water relation parameters measured in response to
      gradual water stress. The results suggest that prolonged cold storage retards
      photosynthetic recovery of seedlings after planting. Higher rates of net
      assimilation in seedlings lifted in May were not directly related to their water
      status. Nonstomatal limitations were the primary factor influencing
      photosynthetic rate. We conclude that the inferior ability of cold-stored
      seedlings to tolerate water stress was due to poor osmotic adjustment and a lag
      in recovery of photosynthesis.

PMID- 14965968
TI  - Effects of "near-lethal" stress on bud dormancy and stem cold hardiness in red
      osier dogwood.
AB  - We studied the effects of "near-lethal" (NL, 47 degrees C for 1 h) heat stress,
      applied to intact shoots of red-osier dogwood (Cornus sericea L.) during early
      (October), deep (November) or late (December) dormancy, on bud dormancy release
      and development of stem tissue cold hardiness under natural conditions and at a
      constant temperature of 0 or 23 degrees C in the dark. The NL heat-stress
      treatment overcame bud dormancy when applied during the early and late stages of
      dormancy. During October and December, all plants in the 23 degrees C + dark post
      stress environment broke bud within 35 and 12 days, respectively, whereas the
      corresponding values for days to bud break in the control plants were more than
      150 and 110 days, respectively. Application of NL heat stress during deep
      dormancy caused only slightly earlier bud break compared to the control plants.
      In the 0 degrees C + dark post-stress environment, all NL heat-treated plants
      died within 9 weeks. Under natural post-stress conditions, bud break in plants
      receiving NL heat stress during early and deep dormancy occurred at the same time
      as in control plants, whereas bud break of plants receiving NL heat stress during
      late dormancy occurred 55 days earlier than in control plants. Under both natural
      and 23 degrees C + dark post-stress conditions, cold hardiness of plants
      receiving NL heat stress during early dormancy was similar to that of controls.
      Application of NL heat stress during deep dormancy hastened the rate of
      deacclimation under the 23 degrees C + dark post-stress conditions but had no
      effect on deacclimation under natural post-stress conditions. Application of NL
      heat stress during late dormancy enhanced deacclimation of plants in both the 23
      degrees C + dark and natural post-stress environments.

PMID- 14965969
TI  - Seasonal nutrient dynamics in white pine and white spruce in response to
      environmental manipulation.
AB  - Seasonal retranslocation in white pine (Pinus strobus L.) and white spruce (Picea
      glauca (Moench) Voss) was examined in response to silvicultural treatments
      (scarification, annual fertilization application, and annual control of competing
      vegetation with herbicide) that changed both environmental conditions and the
      growth rate of the trees. Four years after plantation establishment and initial
      treatment, nutrient accumulation in current-year needles of white pine and
      retranslocation from 1-year-old needles were increased following the vegetation
      control treatment, which increased resource availability (nutrients, water and
      light) and, hence, growth rate. Nutrient accumulation also increased in current
      year white spruce needles following the same treatment, whereas retranslocation
      decreased in 1-year-old white spruce needles. Correlations of retranslocation (N,
      P and K) with growth rate (shoot biomass increment) showed a strong positive
      relationship for white pine and a negative relationship for white spruce.
      Retranslocation of K was correlated with foliar and soil K concentrations; the
      availability of this nutrient was also significantly reduced by vegetation
      control. A general theory for the control of nutrient retranslocation in
      conifers, which is not based exclusively on either sink strength or soil nutrient
      availability, is proposed. We conclude that retranslocation response is species
      specific and related to the potential phenotypic growth response to changing
      environmental conditions and to short-term imbalance in the supply versus the
      demand for nutrients.

PMID- 14965970
TI  - Recovery of photosynthesis in 1-year-old needles of unfertilized and fertilized
      Norway spruce (Picea abies (L.) Karst.) during spring.
AB  - Photosynthetic O(2) evolution and chlorophyll a fluorescence were measured in 1
      year-old needles of unfertilized and fertilized trees of Norway spruce (Picea
      abies (L.) Karst.) during recovery of photosynthesis from winter inhibition in
      northern Sweden. Measurements were made under laboratory conditions at 20 degrees
      C. In general, the CO(2)-saturated rate of O(2) evolution was higher in needles
      of fertilized trees than in needles of unfertilized trees over a wide range of
      incident photon flux densities. Furthermore, the maximum photochemical efficiency
      of photosystem (PS) II, as indicated by the ratio of variable to maximum
      fluorescence (F(V)/F(M)) was higher in needles of fertilized trees than in
      needles of unfertilized trees. The largest differences in F(V)/F(M) between the
      two treatments occurred before the main recovery of photosynthesis from winter
      inhibition in late May. The rate of O(2) evolution was higher in needles of north
      facing branches than in needles of south-facing branches in the middle of May.
      Simultaneous measurements of O(2) exchange and chlorophyll fluorescence indicated
      that differences in the rate of O(2) evolution between the two treatments were
      paralleled by differences in the rate of PS II electron transport determined by
      chlorophyll fluorescence. We suggest that, during recovery of photosynthesis from
      winter inhibition, the balance between carbon assimilation and PS II electron
      transport was maintained largely by adjustments in the nonphotochemical
      dissipation of excitation energy within PS II.

PMID- 14965971
TI  - Nighttime exposure to ozone reduces whole-plant production in Betula pendula.
AB  - For 20 weeks during the growing season, cuttings of one birch clone (Betula
      pendula Roth.) were exposed in the Birmensdorf fumigation chambers to O(3)-free
      air (control) or 75 nl O(3) l(-1). Ozone was supplied either from 1900 until 0700
      h (nighttime regime), from 0700 until 1900 h (daylight regime), or all day (24-h
      regime). By autumn, reductions in whole-plant biomass production, root/shoot
      biomass and stem weight/length ratios were evident in all three O(3) regimes. The
      reductions in cuttings receiving the 24-h O(3) treatment were about twofold
      larger than in cuttings receiving the daylight O(3) treatment. Stomata were open
      at night, and stomatal conductance was about 50% of its maximum daytime value. We
      calculated that the rate of O(3) uptake into leaves in the dark approached 4 nmol
      m(-2) s(-1). Whole-plant production and carbon allocation were more sensitive to
      O(3) during the night than during the day; however, O(3) exposure caused similar
      visible leaf injury in both of the 12-h regimes, although the leaves exposed to
      O(3) at night exhibited delayed O(3)-induced shedding. Overall, changes in
      production and carbon allocation were determined by the external O(3) dose rather
      than by the kind of O(3) exposure, indicating that, at the seasonal scale, the
      internal dose of ozone that was physiologically effective was a constant fraction
      of the external O(3) dose. We conclude that nighttime O(3) exposures should be
      included in the daily time period for determining critical concentrations of O(3)
      causing injury in trees.

PMID- 14965972
TI  - Influence of foliar N on foliar soluble sugars and starch of red spruce saplings
      exposed to ambient and elevated ozone.
AB  - Red spruce (Picea rubens Sarg.) trees growing at high elevation in the
      northeastern United States have experienced decline in recent years but seedlings
      have proved to be relatively tolerant of a wide range of environmental stresses
      in controlled studies. One possible reason for the wide tolerance to stress in
      seedlings is their inherently large pool of carbohydrate reserves, which is
      available for maintenance during and regrowth after periods of stress. We tested
      for the effects of foliar N and exposure to ozone on foliar carbohydrate reserves
      of 20-year-old naturally regenerated saplings. The trees were maintained in
      native soil in 360-l containers for 5 years before the experiment. The year
      before the experiment, trees were fertilized with N,P,K to provide a population
      of trees from N deficient to N sufficient. As foliar N decreased below 0.9%,
      length of current-year shoots and specific needle area of current-year needles
      declined. Foliar N concentration was correlated with foliar sugar and starch
      concentrations, but relationships varied with time of year. Before bud break,
      foliar carbohydrates and N, in general, were positively correlated, and date of
      bud break was delayed in N-deficient trees. During active growth, foliar soluble
      sugars and N were positively correlated, but starch concentrations were
      negatively correlated with N. By late September, neither starch nor sugar
      concentration was correlated with N concentration. Ozone and foliar N
      concentrations did not interact to change foliar carbohydrate concentrations or
      shoot and needle growth in this relatively short-term study.

PMID- 14965973
TI  - A simple, battery-operated, temperature-controlled cuvette for respiration
      measurements.
AB  - We designed a simple, portable, battery-operated, temperature-controlled cuvette
      to measure respiration of small samples of plant tissue in the field. The cuvette
      is built around a peltier cell and is controlled with a data logger. The cuvette
      maintained sample temperature within 0.5 degrees C over a temperature range of 5
      to 45 degrees C and operated for 6-8 h from a 12 V 105 ampere-hour "deep-cycle"
      battery. Based on measurements with this cuvette, we found that, at 15 degrees C,
      CO(2) efflux from dark respiration of white pine (Pinus strobus L.) foliage was
      40% greater during the day than at night.

PMID- 14965974
TI  - Accentuation of gas exchange gradients in flushes of ponderosa pine exposed to
      ozone.
AB  - Two-year-old ponderosa pine seedlings (Pinus ponderosa Laws.) were exposed to
      episodic O(3) concentrations in open-top chambers for two consecutive growing
      seasons (June through September of 1990 and 1991). Near the end of the second
      season of O(3) exposure, gas exchange was measured on needles of surviving
      flushes at saturating CO(2) and photosynthetic photon flux density (PPFD). Both
      photosynthetic capacity (A(sat)) and stomatal conductance to water vapor (g(wv))
      declined linearly with needle age but differences within a flush were also found.
      Gas exchange rates of needles from the base of the current-year flush were
      significantly lower than those of needles from the top of the flush, even though
      age differences between needles were negligible. Although most measurements were
      conducted at saturating CO(2), similar patterns of gas exchange were also found
      at 350 micro mol mol(-1) CO(2), indicating that photosynthesis of needles at the
      bottom of the flush was more strongly affected by O(3) than that of needles at
      the top of the flush, even though the potential for O(3) uptake was probably less
      in needles at the bottom of the flush because of reduced stomatal conductance.
      Carboxylation efficiency (deltaA/deltaC(i)), the linear slope of the A/C(i)
      response, was highly correlated with A(sat), varying with needle age, needle
      position in the flush and O(3) exposure, but the magnitude of the reductions was
      greater than for A(sat). We conclude that susceptibility to O(3) damage among
      needles of an individual seedling varies not only with needle age but also with
      needle position, and that reductions in photosynthetic capacity may not be
      directly attributable to increased uptake of the pollutant. The data also
      indicate the need to consider within-flush variation when estimating whole-plant
      carbon gain and O(3) uptake.

PMID- 14965975
TI  - Reduction of phenolics in mycorrhizas of Larix decidua Mill.
AB  - Soluble and cell-wall-bound phenolics in mycorrhizas of Larix decidua-Laccaria
      amethystea and in nonmycorrhizal fine roots of larch grown in sterile culture
      were analyzed by HPLC. The soluble phenolics p-hydroxybenzoylglucose, p
      hydroxybenzoic acid glucoside, picein, catechin, and epicatechin were identified
      in nonmycorrhizal fine roots. The same phenolics also occurred in mycorrhizas,
      but only in very small quantities compared with those in nonmycorrhizal fine
      roots. The amount of cell-wall-bound ferulic acid was much lower in mycorrhizas
      than in nonmycorrhizal fine roots. Pure mycelia of Laccaria amethystea (Bull.)
      Murr. contained none of the identified phenolics. We conclude that L. amethystea
      induced a large decrease in soluble and cell-wall-bound phenolics in fine roots
      of Larix decidua Mill. that may explain their rapid mycorrhization.

PMID- 14965976
TI  - Effect of lopping on water potential, transpiration, regrowth, (14)C
      photosynthate distribution and biomass production in Alnus glutinosa.
AB  - The effects of light, moderate and heavy branch pruning or lopping treatments
      (resulting in removal of 28-31, 56-60 and 80-82% of the foliage, respectively,
      unlopped control = 0%) were studied in 3-year-old black alder (Alnus glutinosa L.
      Gaertn.) plants. Within 24 h of lopping, transpiration rates decreased and water
      potentials increased. The effects of lopping continued for 48 days. The improved
      water status of the lopped plants enhanced water-use efficiency during the first
      30 days. Regrowth was related to a combination of enhanced net assimilation rates
      during the first 30 days after lopping, use of current photoassimilates and
      stored carbohydrates in the roots (particularly in medium and heavily lopped
      plants) for the production of new leaf area, and delayed leaf senescence. The
      lightly and moderately lopped plants developed 62 and 57% more leaf area,
      respectively, than the unlopped plants, but total leaf area development was
      slower in the heavily lopped plants. Lightly lopped plants produced total biomass
      equivalent to that of unlopped plants, but the moderately and heavily lopped
      plants produced less biomass than the unlopped plants. During the first 30 days
      after lopping, there was a net loss of nodule dry matter and recovery to control
      values did not occur during the period of study. Immediately (24 h) after
      lopping, more (14)C-photosynthate was translocated to the roots of lopped plants
      than to the roots of unlopped plants. When a branch near the base of the main
      stem was fed (14)CO(2), (14)C-photosynthate translocation to the shoot increased
      with increasing intensity of lopping, at 50 days after lopping.

PMID- 14965977
TI  - Exploring the relationship between reflectance red edge and chlorophyll
      concentration in slash pine leaves.
AB  - Chlorophyll concentration is related positively to the point of maximum slope in
      the reflectance spectra of leaves and this point is termed the red edge. The
      reflectance spectra of slash pine (Pinus elliottii Engelm.) needles were measured
      in the field and the chlorophyll concentrations of the same needles were measured
      in the laboratory. The measurement errors for red edge and chlorophyll
      concentration were determined to be 2.2 nm (3% of mean) and 0.35 mg g(-1) (19% of
      mean), respectively. The red edge-chlorophyll concentration relationship was
      strong (r(2) = 0.82, n = 152). A red edge-chlorophyll concentration relationship
      for n = 100 was used with red edge measurements to estimate chlorophyll
      concentration with an rms error of 0.31 mg g(-1) (17% of mean, n = 52). The
      entire red edge-chlorophyll concentration relationship for n = 152 was also used
      with red edge measurements to estimate the chlorophyll concentration of samples
      from an earlier experiment with an rms error of 0.47 mg g(-1) (30% of mean, n =
      38). We conclude that measures of red edge can be used to estimate the
      chlorophyll concentration of detached needles in the field with an accuracy
      similar to that obtained by conventional laboratory measurements.

PMID- 14965978
TI  - Effects of ozone on growth and gas exchange of Eucalyptus globulus seedlings.
AB  - To study the effects of a low concentration of ozone on growth and gas exchange
      in Eucalyptus globulus Labill. seedlings, ozone was applied for 37 days at a
      concentration of 50 ppb for 7 h daily under conditions of low light (250 micro
      mol m(-2) s(-1) (PAR)) and controlled temperature (20 degrees C). The seedlings
      exhibited extreme sensitivity to ozone. The ozone treatment reduced total plant
      biomass but had no effect on the partitioning of assimilate. Photosynthesis,
      stomatal conductance and internal CO(2) concentration were all reduced by ozone.
      The decline in photosynthesis was partly the result of direct effects of ozone on
      the stomata.

PMID- 14965979
TI  - Leaf CO(2) exchange of Erythrina poeppigiana (Leguminosae: Phaseolae) in humid
      tropical field conditions.
AB  - An idealized model was developed to describe leaf CO(2) exchange in the
      leguminous tree Erythrina poeppigiana (Walpers) O.F. Cook under well-watered
      field conditions. Photosynthetic rate in mature leaves (p) was modeled as a
      rectangular hyperbolic function of photon flux density (q) and ambient CO(2)
      concentration (c(a)), relative photosynthetic capacity (pi) was modeled as a
      logistic s-function of leaf age (l(a)), metabolic dark respiration rate (r(m))
      was modeled as an exponential function of leaf temperature (T(l)), and
      photorespiration rate (r(p)) was modeled as a hyperbolic function of c(a).
      Assimilation rate (a(c)) was modeled as the difference between the product of p
      and pi and the sum of r(m) and r(p): a(c) = p(q,c(a))pi(l(a)) - [r(m)(T(l)) +
      r(p)(c(a))]. The model parameters were estimated separately for five sources of
      E. poeppigiana (Clones 2660, 2662, 2687 and 2693 and half-sib Family 2431) from
      field data measured with a portable closed-loop gas exchange system at a humid
      tropical site in Costa Rica. The between-source differences in leaf CO(2)
      exchange characteristics were small, but statistically significant. Aboveground
      biomass production was highest in sources that maintained high relative
      photosynthetic capacity throughout the leaf life span. Quantum yield varied
      between 0.046 and 0.067, and light-saturated assimilation rate (q = 2000 micro
      mol m(-2) s(-1) and T(l) = 28 degrees C) at natural atmospheric c(a) (350 micro
      mol mol(-1)) was 16.8-19.9 micro mol m(-2) s(-1). Increasing c(a) to 1000 micro
      mol mol(-1) resulted in an approximate doubling of the light-saturated
      assimilation rate. Foliole nitrogen concentration, which was 45.3-51.2 mg g(-1)
      in mature leaves, was positively correlated with relative photosynthetic
      capacity. Foliole nitrogen concentration, quantum yield and maximum assimilation
      rate of E. poeppigiana are among the highest values observed in tropical woody
      legumes.

PMID- 14965980
TI  - Growth and nutrition of birch seedlings at varied relative addition rates of
      magnesium.
AB  - Growth and nutrition of hydroponically cultivated birch seedlings (Betula pendula
      Roth.) were investigated at various magnesium (Mg) availabilities. Suboptimum Mg
      conditions were created by adding Mg once per hour in exponentially increasing
      amounts at one of four relative addition rates (R(Mg)): 0.05, 0.10, 0.15 or 0.20
      day(-1). Seedlings given free access to Mg were used as controls. After an
      acclimation period, the relative growth rate of the seedlings attained the same
      value as the corresponding relative rate of Mg addition. In all suboptimum Mg
      treatments, deficiency symptoms in the form of chloroses and necroses developed
      in the older leaves, both during and after the phase of growth acclimation. The
      severity of these symptoms was correlated with the availability of Mg. The
      relative growth rate of seedlings was linearly correlated with plant Mg status.
      The root fraction of the total biomass decreased from 22% in control plants to 8%
      in plants receiving the lowest rate of Mg addition. A shift in Mg availability
      from free access to R(Mg) = 0.05 day(-1) decreased the photosynthetically active
      leaf area per plant weight, despite a concomitant increase in the leaf weight
      ratio (leaf dry weight/plant dry weight) from 0.61 to 0.75. The loss in
      assimilating leaf area was mainly a consequence of enhanced leaf mortality and
      formation of necroses, and to a minor extent attributable to increased carbon
      costs for leaf area production. A decrease in starch concentration was observed
      in leaves showing Mg-deficiency symptoms, whereas the starch concentration in
      healthy leaves was unaffected by Mg availability. It was concluded that shortage
      of carbohydrates constituted the major growth constraint, particularly for roots,
      under Mg-limiting conditions.

PMID- 14965981
TI  - Influence of controlled water supply on shoot and root development of young peach
      trees.
AB  - Three controlled water supply treatments were applied to 1-year-old peach trees
      grown in root observation boxes. The treatments were: I(0), growth medium
      maintained at 50% field capacity; I(1), water supplied when daily net tree stem
      diameter change was negative or zero for 1 day; I(3) as for I(1) except that
      water was applied after net daily stem diameter change was negative or zero for 3
      consecutive days. Trees in treatment I(0) had the greatest mean daily first-order
      shoot growth rates, and trees in treatment I(3) had the lowest shoot growth
      rates. Because leaf production rate (apparent plastochron) of first-order shoots
      was unaffected by treatment, differences in shoot length were due to differences
      in internode extension and not to the number of internodes. Trees in treatment
      I(0) had a greater number of second-order shoot axes than trees in treatment I(1)
      or I(3). Furthermore, an increase in the rate of growth of the first-order shoot
      axis was associated with an increased tendency for branching (i.e., the
      development of sylleptic second-order shoots). Increased leaf length was also
      associated with more frequent watering. Trees in treatment I(0) had the greatest
      root lengths and dry weights, and this was attributed to a greater number of
      first-and second-order (lateral) root axes compared with trees in the I(1) and
      I(3) treatments. The extension rate and apical diameter of first-order roots were
      reduced by the I(3) treatment. The density of second-order roots along primary
      root axes was not affected by any of the treatments.

PMID- 14965982
TI  - Atmospheric CO(2) and the ratio of intercellular to ambient CO(2) concentrations
      in plants.
AB  - Much attention is focused today on predicting how plants will respond to
      anticipated changes in atmospheric composition and climate, and in particular to
      increases in CO(2) concentration. Here we review the long-term global
      fluctuations in atmospheric CO(2) concentration as a framework for understanding
      how current trends in atmospheric CO(2) concentration fit into a selective,
      evolutionary context. We then focus on an integrated approach for understanding
      how gas exchange metabolism responds to current environmental conditions, how it
      previously responded to glacial-interglacial conditions, and how it may respond
      to future changes in atmospheric CO(2) concentration.

PMID- 14965983
TI  - Prediction of stem profile of Picea abies using a process-based tree growth
      model.
AB  - We built a simple tree growth model for Norway spruce (Picea abies (L.) Karst.)
      that describes the biomass and stem radial growth of one tree in a stand. Growth
      is controlled by an external height growth function that accounts for site
      quality. Crown recession is represented by an empirical function that accounts
      for the limitation to crown development caused by mechanical contacts with
      neighboring trees. The model describes biomass growth based on carbon budget
      (photosynthesis, respiration and senescence) and carbon partitioning between
      foliage, stem and root compartments. An internal regulation is introduced based
      on a functional balance between crown and root development. Stem annual growth is
      distributed along the stem by means of an empirical rule. Stem profile is the
      final output of the model and can be used to check the overall consistency of the
      model and as an aid in wood quality studies. The underlying assumptions of the
      model are described.

PMID- 14965984
TI  - Mechanisms of drought response in Thuja occidentalis L. I. Water stress
      conditioning and osmotic adjustment.
AB  - We investigated the extent of osmotic adjustment and changes in transpiration
      rate that occur in response to repeated cycles of water deficit stress in 6-year
      old Thuja occidentalis L. (eastern white cedar) trees. Groups of trees were water
      stress conditioned by repeated exposure to predetermined thresholds of nonlethal
      water stress by withholding water until the predawn water potential fell to -0.9
      (mild conditioning) or -1.4 MPa (moderate conditioning). Both the mild and
      moderate conditioning treatments resulted in a decrease in osmotic potential of
      0.08 to 0.20 MPa and 0.11 to 0.28 MPa, respectively, relative to the well-watered
      controls. Mildly and moderately conditioned trees exhibited an approximately 35
      and 50% reduction in cumulative transpiration, respectively, following at least
      two stress cycles. Transpiration rates of conditioned trees remained below those
      of the well-watered controls even when water potential integrals were similar. We
      conclude that the decrease in transpiration rate was more important than osmotic
      adjustment as a mechanism of response to repeated water stress.

PMID- 14965985
TI  - Mechanisms of drought response in Thuja occidentalis L. II. Post-conditioning
      water stress and stress relief.
AB  - We examined the extent of osmotic adjustment and the changes in relative water
      content (RWC) and transpiration rate (i.e., relative stomatal function) that
      occur in water-deficit-conditioned 6-year-old Thuja occidentalis L. (eastern
      white cedar) trees in response to a severe drought. Trees conditioned by
      successive cycles of mild or moderate nonlethal water stress (conditioning) and
      nonconditioned trees were exposed to drought (i.e., -2.0 MPa predawn water
      potential) to determine if water deficit conditioning enhanced tolerance to
      further drought stress. Following drought, all trees were well watered for 11
      days to evaluate how quickly osmotic potential, RWC and transpiration rate
      returned to preconditioning values. Both nonconditioned trees and mildly
      conditioned trees exhibited similar responses to drought, whereas moderately
      conditioned trees maintained higher water potentials and transpiration rates were
      38% lower. Both conditioned and nonconditioned trees exhibited a similar degree
      of osmotic adjustment (-0.39 MPa) in response to drought relative to the well
      watered control trees. The well-watered control trees, nonconditioned trees and
      mildly conditioned trees had similar leaf RWCs that were about 3% lower than
      those of the moderately conditioned trees. Following the 11-day stress relief,
      there were no significant differences in osmotic potential between the well
      watered control trees and any of the drought-treated trees. Daily transpiration
      rates and water potential integrals (WPI) of all drought-treated trees approached
      those of the well-watered control trees during the stress relief period. However,
      the relationship between cumulative transpiration and WPI showed that previous
      exposure to drought stress reduced transpiration rates. Leaf RWC of the
      moderately conditioned trees remained slightly higher than that of the
      nonconditioned and mildly conditioned trees.

PMID- 14965986
TI  - Effects of curtain-like pruning on distribution and seasonal patterns of
      carbohydrate reserves in plane (Platanus acerifolia Wild) trees.
AB  - The maintenance of plane trees (Platanus acerfolia Wild) by regular curtain-like
      pruning during the vegetative period induced modifications in the distribution
      and seasonal patterns of carbohydrate reserves in the perennial parts. The
      unpruned trees were characterized by high and fairly constant concentrations of
      starch in roots > 5 cm in diameter and a decreasing gradient of starch from the
      base to the top of the trunk. Starch also accumulated at the trunk-branch
      junction and at the base of large branches. Curtain-like pruning caused the
      starch gradient in the trunk to disappear and induced well marked seasonal
      variations in the starch concentration of roots > 5 cm in diameter. Pruning also
      eliminated the accumulation of starch at the trunk-branch junction during summer,
      but it had no effect on the accumulation of starch at the base of large branches.
      Concentrations and seasonal fluctuations of carbohydrates in roots < 0.5 cm in
      diameter were similar in both pruned and unpruned trees. Repeated cuts or "short
      head pruning" induced the formation of excrescences at the tips of branches that
      accumulated starch.

PMID- 14965987
TI  - Dormancy release and chilling requirement of buds of latitudinal ecotypes of
      Betula pendula and B. pubescens.
AB  - Bud burst and dormancy release of latitudinal ecotypes of Betula pendula Roth and
      B. pubescens Ehrh. from Denmark ( approximately 56 degrees N), mid-Norway (
      approximately 64 degrees N) and northern Norway ( approximately 69 degrees N)
      were studied in controlled environments. Dormant seedlings were chilled at 0, 5
      or 10 degrees C from October 4 onward and then, at monthly intervals from mid
      November to February, batches of seedlings were held at 15 degrees C in an 8-h
      (SD) or 24-h (LD) photoperiod to permit flushing. A decline in days to bud burst
      occurred with increasing chilling time in all ecotypes. In November, after 44
      chilling days, time to bud burst was least in plants chilled at 0 and 5 degrees
      C. The difference diminished with increasing chilling time, and in February,
      after 136 chilling days, bud burst was earliest in plants chilled at 10 degrees
      C. Long photoperiods during flushing significantly reduced thermal time after
      short chilling periods (44 and 74 days), but had no effect when the chilling
      requirement was fully met after 105 or more chilling days. No significant
      difference in these responses was found between the two species. In both species,
      chilling requirement decreased significantly with increasing latitude of origin.
      Bud burst was normal in seedlings overwintered at 12 degrees C, but was erratic
      and delayed in seedlings overwintered at 15 and especially at 21 degrees C,
      indicating that the critical overwintering temperature is between 12 and 15
      degrees C. We conclude that there is little risk of a chilling deficit in birch
      under Scandinavian winter conditions even with a climatic warming of 7-8 degrees
      C. The likely effects of a climatic warming include earlier bud burst, a longer
      growing season and increased risk of spring frost injury, especially in high
      latitude ecotypes.

PMID- 14965988
TI  - Variation in the ratio of shoot silhouette area to needle area in fertilized and
      unfertilized Norway spruce trees.
AB  - We compared the range and variation in shoot silhouette area to projected leaf
      area ratio (SPAR) in fertilized and unfertilized (control) Norway spruce (Picea
      abies (L.) Karst.) trees. We measured SPAR for several view directions of 169
      shoots at different depths in the crown of fertilized and control trees. There
      was an increase in SPAR with depth in the crown in both control and fertilized
      trees. In the fertilized trees, however, mean SPAR was larger overall, the
      increase with depth in the crown was steeper, and there was a larger variation in
      SPAR with inclination and rotation angle of the shoot (relative to the view
      direction). In particular, shoots in the lower crown of fertilized trees were
      rotationally asymmetrical ("flat") and had high values of the maximum ratio of
      shoot silhouette area to projected leaf area (SPAR(max)). Differences in SPAR
      between fertilized and control trees were explained by changes in shoot structure
      in response to fertilization and shading. Shoots of fertilized trees were larger
      and had more needle area than shoots of control trees. However, the ratio of
      needle area to shoot size was smaller in fertilized trees than in control trees,
      implying less within-shoot shading and, consequently, a larger SPAR. Also, the
      increase in SPAR with increased shading (depth in the crown) could be explained
      by a decrease in the ratio of needle area to shoot size. In addition, because
      fertilized trees had more needle area than control trees, the effect of shading
      at a given depth in the crown was more pronounced in fertilized trees than in
      control trees.

PMID- 14965989
TI  - Physiological, morphological and anatomical responses of Fraxinus mandshurica
      seedlings to flooding.
AB  - Two-year-old Fraxinus mandshurica Rupr. var. japonica Maxim. seedlings were
      flooded to 8 cm above soil level for 70 days. The flooding treatment altered the
      growth, morphology, stem anatomy and ethylene production of the seedlings.
      Although flooding did not affect height growth, it stimulated diameter growth of
      the submerged stems by increasing both the number and size of wood fibers
      produced; however, the thickness of the cell walls of the wood fibers was reduced
      by flooding. In response to the flooding treatment, the seedlings formed abundant
      hyperhydric tissues, originating from the vicinity of lenticels on the surface of
      the flooded stems, and adventitious roots, which grew through the hyperhydric
      tissues. Aerenchyma tissues were observed in the bark of the adventitious roots.
      The flooding treatment did not affect dry weight increment of leaves and stems,
      but it reduced the total dry weight increment of the root system even though it
      promoted adventitious root formation. Flooding also enhanced ethylene production
      in the submerged portions of stems. The potential roles of flood-induced ethylene
      in cambial growth and adventitious root formation in flooded plants are
      discussed.

PMID- 14965990
TI  - Methods for combining phenological time series: application to bud burst in birch
      (Betula pendula) in Central Finland for the period 1896-1955.
AB  - We compared four methods for combining separate fragmentary phenological time
      series into a single long reliable series. The systematic linear effect of
      differences in observers, genotypes, geography and climate at the observation
      points produces disturbing variation in the observations and bias in the means of
      some time points. The three methods based on the adjustment of individual series
      eliminated the disturbing variation and bias. The methods were compared based on
      phenological observations of bud burst in birch (Betula pendula Roth). The method
      based on a linear mixed model of analysis of variance and the maximum likelihood
      estimation was considered preferable to the other methods.

PMID- 14965991
TI  - In vitro regeneration of Pacific silver fir (Abies amabilis) plantlets and
      histological analysis of shoot formation.
AB  - A protocol is described for the in vitro propagation of Abies amabilis (Dougl.)
      Forbes. Over 60% of the cotyledonary explants from 5-day-old cotyledons formed
      shoots when cultured for 7 days on Schenk and Hildebrandt's (SH) medium
      containing 10 micro M N(6)-benzyladenine (BA) followed by another 7 days on SH
      medium containing 10 micro M each of BA and zeatin. Shoot multiplication was
      unsuccessful. Seventeen percent rooting was obtained after pulsing for 4 h in 1
      mM indole-3-butyric acid and planting pulsed shoots in 1/1 (v/v)
      perlite/vermiculite. Cell clusters (promeristemoids) of five to seven cells were
      observed on the cotyledonary explants after 7 days of culture in the presence of
      cytokinin. These cells developed further into meristematic domes and apical
      meristems. In the absence of cytokinin, stomata and resin canals reached
      maturity, whereas cells within the cortex became vacuolated and developed into
      palisade and spongy mesophyll.

PMID- 14965992
TI  - Ecophysiological attributes of the native Acer saccharum and the exotic Acer
      platanoides in urban oak forests in Pennsylvania, USA.
AB  - When the exotic Acer platanoides L. (Norway maple) and the native A. saccharum
      Marsh. (sugar maple) grow together in the understories of urban Quercus forests
      in the eastern USA, average annual height growth increments are nearly twice as
      large in A. platanoides as in A. saccharum, 19.26 +/- 3.22 versus 10.01 +/- 1.69
      cm. We examined several ecophysiological mechanisms that might be associated with
      the superior invasive ability and growth of A. platanoides in two urban oak
      forests in Pennsylvania. Leaf longevity was 12 days greater in A. platanoides
      than in A. saccharum. In addition, leaf mass/leaf area ratio was greater in A.
      platanoides than in A. saccharum (2.67 +/- 0.03 versus 2.32 +/- 0.02 mg cm(-2));
      however, leaf thickness was significantly lower in A. platanoides than in A.
      saccharum suggesting that A. platanoides contains more dense palisade and
      mesophyll cell layers than A. saccharum. Field net photosynthesis (mass basis)
      and photosynthetic light response curves (area basis) indicated significantly
      greater carbon assimilation, and nitrogen and phosphorus use efficiencies in A.
      platanoides than in A. saccharum. Acer platanoides also exhibited higher water
      use efficiency than A. saccharum (0.88 +/- 0.12 versus 0.32 +/- 0.09 mmol CO(2)
      mol(-1) H(2)O). Acer platanoides exhibited significantly lower osmotic potentials
      than A. saccharum, but a similar relative water content at zero turgor. We
      conclude that A. platanoides utilizes light, water and nutrients more efficiently
      than A. saccharum.

PMID- 14965993
TI  - Acid phosphatase activity and phosphorus nutrition in Scots pine needles.
AB  - From March to October, acid phosphatase activity and phosphorus (P) concentration
      were measured in four needle age classes of the upper and lower crowns of
      fertilized and unfertilized Scots pine (Pinus sylvestris L.) trees. Negative
      correlations between acid phosphatase activity and P concentration were observed
      in current-year needles and in needles in the upper part of the crown, whereas
      there was a positive correlation between enzyme activity and P concentration in
      older needles and in needles in the lower part of the crown. In May and October,
      needles of all ages showed increased acid phosphatase activity. The most
      sensitive response of acid phosphatase activity to phosphate supply and
      phosphorus status of the whole tree was seen in current-year needles on the first
      whorl where a 300% increase in acid phosphatase activity was observed in response
      to a decrease in foliar P concentration of 1.7-1.8 mg P g(DW) (-1).

PMID- 14965994
TI  - Growth and nutrient use efficiency of water tupelo seedlings in flooded and well
      drained soil.
AB  - Growth characteristics and nutrient utilization rate of Nyssa aquatica L.
      seedlings grown in pots containing flooded or well-drained soil were compared in
      a greenhouse study. For most of the growing season, relative height and diameter
      growth rates, and biomass accumulation rates were greater for seedlings in
      flooded soil than for seedlings in well-drained soil. The concentration of Fe in
      the roots of seedlings in flooded soil was almost tenfold greater than that of
      seedlings in well-drained soil. However, flooding had no effect on foliar Fe
      concentrations. The flooding treatment resulted in decreased concentrations of N
      in all component parts and increased concentrations of P in the roots and stem,
      but it had no effect on foliar P concentrations. In response to flooding, foliar
      K concentrations decreased, whereas the concentration of K in the roots
      increased. Flooding had no effect on the K concentration of the stem. Seedlings
      in flooded soil produced more total biomass per milligram of nutrient absorbed
      than seedlings in well-drained soil, suggesting that N. aquatica seedlings are
      more efficient at producing biomass and height growth under hydric conditions
      than under mesic conditions.

PMID- 14965995
TI  - Changes in respiration and chemical content during autumnal senescence of Populus
      tremuloides and Quercus rubra leaves.
AB  - Changes in respiration rate, chemical content and chemical concentration were
      measured in leaves of field-grown Populus tremuloides Michx. and Quercus rubra L.
      trees throughout the growing season and autumnal senescence. Chlorophyll, soluble
      sugar, N, P, K and Mg contents and concentrations all declined during leaf
      senescence, whereas Ca content and concentration increased. Leaf dry mass per
      area declined 24 and 35% in P. tremuloides and Q. rubra, respectively, during
      senescence. In leaves of both species, respiration rates peaked during leaf
      expansion in the spring and then declined, as a result of reduced cytochrome
      mediated respiration, to reach relatively constant rates by midsummer. In
      senescing P. tremuloides leaves, respiration rates remained relatively constant
      until mid-October and then declined rapidly. In senescing Q. rubra leaves,
      respiration rates increased in late September, as a result of the appearance of
      residual respiration that could not be reduced by respiratory inhibitors, and
      then declined quickly in early November. No changes in alternative pathway
      respiratory activity were observed in leaves of either species during senescence
      until late autumn when rates declined. Because respiration rates were correlated
      with both leaf sugar and nitrogen content during leaf senescence, we conclude
      that respiration rates were maintained or increased during leaf senescence to
      supply energy for degradation and mobilization of chemical constituents.

PMID- 14965996
TI  - Physiological responses to water stress and waterlogging in Nothofagus species.
AB  - Gas exchange and water relations were investigated in Nothofagus solandri var.
      cliffortioides (Hook. f.) Poole (mountain beech) and Nothofagus menziesii (Hook.
      f.) Oerst (silver beech) seedlings in response to water stress and waterlogging.
      At soil matric potentials (Psi(soil)) above -0.005 MPa, N. solandri had
      significantly higher photosynthetic rates (A), and stomatal and residual
      conductances (g(sw) and g(rc)), and lower predawn xylem water potentials
      (Psi(predawn)) than N. menziesii. The relative tolerance of plants to water
      stress was defined in terms of critical soil matric potential (Psi(cri)) and
      lethal xylem water potential (Psi(lethal)). The estimated values of Psi(cri) and
      Psi(lethal) were -1.2 and -7 MPa, respectively, for N. solandri, and -0.7 and -4
      MPa, respectively, for N. menziesii. Photosynthesis was sustained to a xylem
      water potential (Psi(xylem)) of -7 MPa in N. solandri compared with -4 MPa in N.
      menziesii. Following rewatering, both A and Psi(xylem) recovered quickly in N.
      solandri, whereas the two variables recovered more slowly in N. menziesii. During
      the development of water stress, nonstomatal inhibition significantly affected A
      in both N. solandri and N. menziesii. Nothofagus menziesii was more susceptible
      to inhibition of A by waterlogging than N. solandri. However, the tolerance of N.
      solandri to severe waterlogging was also limited as a result of a failure to form
      adventitious roots, suggesting a lack of adaptation to these conditions. The
      differences in tolerance to water stress and waterlogging between the two species
      are consistent with the distribution patterns of N. solandri and N. menziesii in
      New Zealand.

PMID- 14965997
TI  - Effects of mist acidity and ambient ozone removal on montane red spruce.
AB  - Recent forest studies have established that high-elevation (> 900 m) populations
      of red spruce (Picea rubens Sarg.) in the northeastern USA are declining. Because
      it has been suggested that changes in air quality are responsible for the
      decline, we examined the effects of acidic mists and ozone on several biochemical
      and growth parameters in mature montane red spruce. We used branch-sized
      environmental chambers to introduce mists of controlled composition and exclude
      ambient clouds and ozone from individual branches within a tree. Mists consisting
      of distilled water increased the end-of-season pigment concentration and shoot
      length of enclosed branches relative to ambient or artificial mists. Needle and
      twig weights and starch concentrations were not significantly altered by the
      acidic mist treatments. Removal of ambient ozone had no apparent effect on the
      variables measured.

PMID- 14965998
TI  - Systematic variation in xylem hydraulic capacity within the crown of white ash
      (Fraxinus americana).
AB  - A 7-m tall white ash tree (Fraxinus americana Marsh.) was dissected, and
      hydraulic parameters of the xylem were determined by inducing a steady-state flow
      of water through the stem segments and monitoring volume and velocity flow rates.
      Leaf-specific conductivity (LSC) was highest in the main stem and lowest in some
      of the leaf-bearing lateral shoots. The LSC was higher in the main stem than in
      branches and higher in primary than in secondary branch axes. Terminal leaf
      bearing shoots were larger and had a significantly greater mean LSC than
      subjacent lateral shoots. A significant reduction in LSC was associated with the
      transition between 1- and 2-year-old growth. In branches of the same age, there
      was a close correspondence among LSC, branch position and branch size. The
      average LSC of leaf-bearing shoots from south-facing branches was 43% greater
      than that of shoots from north-facing branches. Within-crown variation in LSC was
      associated with variation in velocity flow rate (V). By contrast, the ratio of
      potentially functional xylem area to supported leaf area (A(pf)/A(l)) was
      relatively stable throughout the crown. Stratification of stems by Strahler order
      accounted for approximately 70% of the total variation in LSC. These results
      suggest that (1) there exists a systematic pattern of variation in LSC
      distribution within the crown of white ash, (2) within-crown variability in LSC
      is primarily the result of variation in mean vessel diameter, and (3) there is a
      physiological linkage between LSC and crown morphology that is maintained through
      a positive feedback mechanism during branch ontogeny.

PMID- 14965999
TI  - Carbon isotope variation in Douglas-fir foliage: improving the delta(13)C-climate
      relationship.
AB  - The natural abundance of stable carbon isotopes in the annual rings of forest
      trees is used as a tracer of environmental changes such as climate and
      atmospheric pollution. Although tree-ring delta(13)C varies by about 2 per
      thousand from year to year, variability within the foliage can be as high as 6
      per thousand. Recent studies have shown that branch length affects stomatal
      response, which influences the integrated foliar delta(13)C signal. To improve
      the ability of delta(13)C to predict climate differences, we examined the
      relationship between branch length and foliar delta(13)C in Pseudotsuga menziesii
      (Mirb.) Franco from four sites across a steep climate gradient in Oregon. The
      transect spanned the boundary between the ranges of the coastal variety, P.
      menziesii var. menziesii (three sites), and the Rocky Mountain variety, P.
      menziesii var. glauca (one site). At the most maritime site, branch length
      explained 76% of within-site variation of 5 per thousand, whereas at the harshest
      site, branch length accounted for only 15% of this variation. We considered the
      possibility that cavitation in the water-conducting xylem obscures the branch
      length effect in the harsher climates. Cavitation, as measured by dye perfusion,
      was most extensive at sites where the branch length effect in the coastal variety
      was weakest. Trees at the site with the most substantial cavitation displayed
      seasonal xylem refilling. Branch length standardization significantly improved
      the relationship between delta(13)C and climate. With standardization to constant
      length, delta(13)C values were significantly related to the degree that climatic
      variables, as modeled with a forest growth simulation model, constrain
      transpiration (R(2) = 0.69, P < 0.0001). Without standardization, the R(2) was
      0.27. We conclude that sampling standard length branches or tree rings from trees
      of similar shape and size is desirable when seeking correlations between isotopic
      composition and climate.

PMID- 14966000
TI  - Photosynthesis and canopy characteristics in genetically defined families of
      silver birch (Betula pendula).
AB  - Net photosynthetic rates (A) of leaves in upper and lower crown layers (A(upper)
      and A(lower)), leaf area index (LAI), mean tilt angle (MTA), several leaf
      characteristics, and volume growth were observed in fast- and slow-growing
      families of a 14-year-old full-sib and half-sib family progeny test of Betula
      pendula Roth. Each measure of net photosynthetic rate was calculated after
      correcting measured net photosynthesis for the effects of environmental
      variables. The differences in A(upper) and LAI among families were significant.
      The proportions of the total variance assigned to family for A(upper), A(lower)
      and LAI were 33.64, 28.93 and 54.99%, respectively. The mean A(upper) and LAI of
      the fast-growing families were significantly higher than those of the slow
      growing families, whereas the mean A(lower) of the fast-growing families was
      significantly lower than that of the slow-growing families. There were also
      significant differences among families in leaf size, leaf shape, and the ratios
      leaf fresh weight/area and leaf dry weight/area. Between 27.55 and 54.55% of the
      total variance in these characteristics could be assigned to the family effect.
      Volume growth was positively correlated with A(upper) and LAI, but it was most
      strongly correlated with A(upper) x LAI.

PMID- 14966001
TI  - Characterization of BspA, a major boiling-stable, water-stress-responsive protein
      in aspen (Populus tremula).
AB  - We identified a novel 66 kDa boiling-stable protein (BspA) in cultured shoots of
      aspen (Populus tremula L.) which was highly expressed in response to gradual
      water stress. The BspA protein, which was highly expressed as early as 1 h after
      initiation of a drought treatment, accumulated during progressive water stress,
      decreased on rehydration, and was expressed in response to abscisic acid (ABA)
      application, as detected by SDS-PAGE protein analysis and Western blotting. Anti
      BspA antibodies also cross-reacted with a 119 kDa protein. The 119 kDa protein
      was also induced by water stress, but it was detected only in the total protein
      fraction and not in the heat-stable fraction. The BspA protein cross-reacted with
      antibodies raised against a water-stress-responsive protein isolated from the
      African resurrection plant Craterostigma plantagineum Hochst. The N-terminal
      amino acid sequence of BspA was determined and exhibited high homology with the
      wheat germins GF-2.8 and GF-3.8. The BspA protein was the only major, water
      stress-responsive boiling-stable protein detected in aspen.

PMID- 14966002
TI  - Role of nitrogen remobilization from old leaves for new leaf growth of Eucalyptus
      globulus seedlings.
AB  - Six-month-old Eucalyptus globulus Labill. seedlings were grown in sand culture
      irrigated with a nutrient solution containing 6.0 mol N m(-3) for 3 months
      (November-January). Before rapid growth began in February, seedlings were
      repotted and irrigated with either 6.0 mol N m(-3) (High-N treatment) or 1.0 mol
      N m(-3) (Low-N treatment). Seedlings were analyzed during the subsequent flush of
      growth to determine the role of old leaves, and in particular the leaf protein
      Rubsico, as a source of N for new leaf growth. During spring growth, the N
      content of old leaves of High-N seedlings decreased with decreasing leaf dry
      weight, although there was no change in leaf number. In High-N seedlings, the net
      loss of N from old leaves provided less than 10% of the N used for new leaf
      growth, and the new leaves quickly became the dominant sink for N. In contrast,
      in Low-N seedlings, the net loss of N from old leaves provided 44% of the N used
      for new leaf growth. During the period of spring growth, the amount of soluble
      proteins recovered from old leaves of Low-N seedlings dropped, but there was no
      change in the content of either Rubisco or chlorophyll. The photosynthetic
      capacity of old leaves remained constant throughout the study period, and there
      was no evidence that N was remobilized from Rubisco.

PMID- 14966003
TI  - Seasonal variation in photochemical activity and hardiness in clones of Norway
      spruce (Picea abies).
AB  - We investigated changes in photochemical activity and cold hardiness of detached
      needles of three clones of Picea abies (L.) Karst. by measuring variable
      chlorophyll fluorescence (F(v)/F(m)), before and after artificial freezing, from
      September to June. Photochemical activity varied considerably during the study,
      but only minor differences in photochemical activity among the clones were
      observed before freezing. Photochemical activity was high during early fall and
      then declined from November until April. Photochemical activity was at a minimum
      in April and then increased quickly to high values in May. During the period from
      late September to October, and also during the winter, differences in F(v)/F(m)
      ratios after artificial freezing to below -10 degrees C were observed among
      clones, indicating clonal differences in cold hardiness and hardiness
      development. The clone having an average height of 2.3 m after 11 years showed
      consistently lower cold hardiness than clones that had reached average heights of
      4.0 and 5.0 m. There were also differences in the temperature requirement for bud
      flushing among clones.

PMID- 14966004
TI  - Micropropagation of Elaeagnus angustifolia from mature trees.
AB  - Multiple shoots were obtained from nodal segments of mature trees of Elaeagnus
      angustifolia L. cultured on MS medium (Murashige and Skoog 1962) supplemented
      with 0, 0.88 or 2.22 micro M N(6)-benzyladenine. When nodal segments taken from
      the in vitro proliferated shoots were cultured under the same conditions,
      additional multiple shoots were obtained. Rooting of the in vitro propagated
      shoots was achieved on full strength MS medium or on MS supplemented with 2.46
      micro M indole-3-butyric acid. Regenerated plantlets were acclimatized and
      successfully transplanted to soil.

PMID- 14966005
TI  - Climate influences the leaf area/sapwood area ratio in Scots pine.
AB  - We tested the hypothesis that the leaf area/sapwood area ratio in Scots pine
      (Pinus sylvestris L.) is influenced by site differences in water vapor pressure
      deficit of the air (D). Two stands of the same provenance were selected, one in
      western Scotland and one in eastern England, so that effects resulting from age,
      genetic variability, density and fertility were minimized. Compared with the
      Scots pine trees at the cooler and wetter site in Scotland, the trees at the
      warmer and drier site in England produced less leaf area per unit of conducting
      sapwood area both at a stem height of 1.3 m and at the base of the live crown,
      whereas stem permeability was similar at both sites. Also, trees at the drier
      site had less leaf area per unit branch cross-sectional area at the branch base
      than trees at the wetter site. For each site, the average values for leaf area,
      sapwood area and permeability were used, together with values of transpiration
      rates at different D, to calculate average stem water potential gradients.
      Changes in the leaf area/sapwood area ratio acted to maintain a similar water
      potential gradient in the stems of trees at both sites despite climatic
      differences between the sites.

PMID- 14966006
TI  - Influence of environment, fertilizer and genotype on shoot morphology and
      subsequent rooting of birch cuttings.
AB  - Differences in rooting ability of birch (Betula pubescens J.F. Ehrh.) cuttings
      were observed as a result of differences in genotype and physiology of the stock
      plants. The uniformity in response among cuttings from micropropagated plants
      compared with cuttings from seed plants confirmed the advantage of using
      micropropagated plants to study environmental effects. Shoot morphology of the
      seed stock plants was influenced by both photoperiod and thermoperiod. A
      day/night temperature of 15/25 degrees C reduced stem elongation compared with a
      day/night temperature of 25/15 degrees C regardless of photoperiod, and a
      continuous light regime resulted in more shoots per plant in both temperature
      regimes than a 16-h photoperiod. A reduction in the supply of macronutrients did
      not influence shoot morphology, but increased rooting substantially and seemed to
      override the effects of environmental factors. In cuttings of seed plants, the
      highest rooting percentage and number of roots were obtained in a 16-h
      photoperiod with a day/night temperature of 15/25 degrees C. In micropropagated
      stock plants, there was a positive correlation between shoot length and number of
      leaves per shoot and topographical distribution of light within the plants, but
      there was no correlation between these parameters and rooting ability of the
      cuttings. A rooting temperature of 16 degrees C delayed the rate of root
      production compared with the rate at higher temperatures, but the final rooting
      percentage was the same over the range from 16 to 28 degrees C. Root branching
      increased with temperature. At all temperatures, there was a large increase in
      sucrose content at the base of the cuttings during rooting, whereas the
      concentration of nontranslocated sugars remained constant. The carbohydrate
      content at the base of cuttings from micropropagated stock plants was three times
      higher than at the base of cuttings from seed stock plants, but the higher
      carbohydrate content was not correlated with a higher rooting potential.

PMID- 14966007
TI  - Water relations and growth of loblolly pine seedlings planted under a shelterwood
      and in a clear-cut.
AB  - We investigated the influence of shelterwood conditions on water relations and
      growth of loblolly pine (Pinus taeda L.) seedlings on two harsh sites in eastern
      Texas. Site I was harvested to provide four overstory density treatments (0, 2.3,
      4.6 and 9.2 m(2) of residual basal area per ha). To quantify the effects of
      overstory competition, trenched and nontrenched subplots, each containing 25 one
      year-old seedlings, were established within each overstory treatment plot, and
      predawn and midday water potentials (Psi(w)), seedling growth and survival were
      measured during the growing season. Leaf area and seedling biomass partitioning
      were measured at the end of the growing season. Site II was harvested to provide
      two overstory density treatments (0 and 6.9 m(2) ha(-1)) and planted with one
      year-old loblolly pine seedlings. Seedling Psi(w), stomatal conductance (g(wv)),
      transpiration flux density (E), leaf area, height and survival were determined.
      On Site I, seedling Psi(w) increased with increasing overstory basal area,
      whereas trenching only substantially affected Psi(w) of seedlings in the 9.2 m(2)
      ha(-1) overstory treatment. Growth was not affected by overstory treatment or
      trenching. On Site II, Psi(w) and g(wv) were highest during the morning hours and
      lowest in the afternoon, whereas E peaked in the afternoon. Vapor pressure
      deficits and photosynthetic photon flux density were major factors in determining
      g(wv) differences between treatments. On individual days, the presence of an
      overstory increased Psi(w) and reduced both g(wv) and E. On Site II, leaf area
      was affected by overstory treatment throughout most of the study. We conclude
      that the presence of an overstory can have ameliorative effects on harsh sites at
      the western fringe of the loblolly pine natural range.

PMID- 14966008
TI  - Interaction between indole-3-acetic acid and ethylene in the control of tracheid
      production in detached shoots of Abies balsamea.
AB  - We investigated the interaction between indole-3-acetic acid (IAA) and ethylene
      in the regulation of the seasonal periodicity of tracheid production in 1-year
      old balsam fir (Abies balsamea (L.) Mill.) cuttings collected at different times
      during the dormant period. The cuttings were left with their buds intact or were
      debudded and treated either apically with IAA or 2-chloroethylphosphonic acid
      (Ethrel) in lanolin, laterally with IAA or Ethrel in lanolin, or basally with
      Ethrel, Co(2+) or Ag(+) in deionized water. The treated cuttings were then
      cultured for up to 5 weeks under controlled environment conditions favorable for
      cambial growth. No change in ethylene evolution was detected during the rest
      quiescence transition, when IAA-induced tracheid production increased. The
      induction of cambial reactivation by IAA was associated with a rise in ethylene
      evolution, but there was no consistent relationship among IAA concentration,
      tracheid number and ethylene emission. Neither Ethrel, Co(2+) nor Ag(+) affected
      tracheid production when applied basally, except for 10 and 100 micro M Ethrel
      and 100 micro M Co(2+), which were inhibitory. In contrast, ethylene evolution
      was promoted by Ethrel and inhibited by Co(2+), whereas Ag(+) had no effect.
      Similarly, applying Ethrel apically or laterally increased ethylene evolution,
      but did not promote tracheid production except in the treatment in which 1 mg
      Ethrel g(-1) lanolin was applied laterally to cuttings treated apically with 0.1
      mg IAA g(-1) lanolin, and in the treatment in which 10 mg Ethrel g(-1) lanolin
      was applied laterally to budded cuttings. We conclude that (1) ethylene evolution
      is not specifically associated with IAA-induced tracheid production, (2) ethylene
      does not mimic the promoting effect of IAA on tracheid production, and (3)
      ethylene can promote tracheid production, but only when its application results
      in a localized unphysiologically high concentration in the cambial region, which,
      in turn, induces an accumulation of IAA.

PMID- 14966009
TI  - The effect of defruiting at different stages of fruit development on leaf
      photosynthesis of "Golden Delicious" apple.
AB  - Net photosynthetic rates (A) of leaves on 11-year-old, field-grown apple trees
      (Malus domestica Borkh. cv. Golden Delicious) were measured after removal of
      fruits at four different stages of development. Defruiting decreased A by 21, 42,
      27 and 7% when fruits were growing at 311, 293, 229 and 113 mg(DW) day(-1),
      respectively. Photosynthesis was inhibited more in the afternoon than in the
      morning, but it was not affected during the first 8 h after fruit removal.
      Inhibition of A was positively correlated with crop sink strength, but it was not
      correlated with fruit relative growth rate or crop load. Defruiting decreased A
      at saturating irradiances (PPFD > 1000 micro mol m(-2) s(-1)), but did not modify
      the apparent quantum yield of single leaves. These results suggest that the
      overall effect of defruiting on carbon fixation is negligible in dense canopies,
      but it may be significant in sparse canopies and in single shoots.

PMID- 14966010
TI  - Genetic variation in rooting ability of loblolly pine cuttings: effects of auxin
      and family on rooting by hypocotyl cuttings.
AB  - After about 20 days, hypocotyl cuttings from 20-day-old loblolly pine (Pinus
      taeda L.) seedlings rooted easily in the presence of the auxin indole-3-butyric
      acid (IBA), with roots forming directly from xylem parenchyma. In contrast, woody
      cuttings from 1-2-year-old hedged seedlings formed roots indirectly from callus
      tissue in 60-90 days, but IBA had little effect on rooting. Variation in rooting
      among hypocotyls from both half- and full-sib families was highly significant in
      response to IBA, and rooting did not occur within 20 days unless IBA was applied.
      Hypocotyls from poor rooting families tended to produce fewer roots per cutting
      than hypocotyls from good rooting families. Rooting by woody cuttings and
      hypocotyl cuttings from the same nine full-sib families was weakly correlated,
      raising the possibility that at least some common genetically controlled
      processes were affecting rooting by both types of cutting. The phytotropin N-1
      naphthylphthalamic acid (NPA), supplied at 1 micro M with 10 micro M IBA,
      significantly inhibited rooting by hypocotyl cuttings from both good and poor
      rooting families, but there was no significant family x treatment interaction.
      Family variation in rooting ability may be a function of the frequency of
      occurrence of auxin-responsive cells in the hypocotyls.

PMID- 14966011
TI  - Canopy dynamics and the morphological development of Abies balsamea: effects of
      foliage age on specific leaf area and secondary vascular development.
AB  - Data were collected from two branches from each whorl of nine open-grown Abies
      balsamea (L.) Miller trees to test the hypothesis that specific leaf area (SLA,
      m(2) projected fresh leaf area kg(-1) oven-dry foliage) is constant among five
      foliage age classes (current-year, 1-year-old, 2-year-old, 3-year-old and 4-year
      old-plus). Between-tree variation in SLA was greater than within-tree variation.
      Differences in SLA among the foliage age classes were small, but statistically
      significant, showing a trend of decreasing SLA with increasing foliage age. Using
      data from two previous biomass studies, we found that three different methods of
      calculating SLA of individual trees produced the same projected leaf area
      estimates. To test the hypothesis that foliage mass increases with foliage age as
      a result of secondary xylem or phloem development, we examined the secondary
      vascular development of foliage collected from five age classes and three crown
      sections in an open-grown A. balsamea. The number of rows of xylem cells was not
      constant among foliage age classes, but the differences were small and showed no
      consistent pattern of change with foliage age. Total number of rows of phloem
      cells increased, number of living rows of phloem cells decreased, and the number
      of rows of nonliving crushed phloem cells increased with foliage age.

PMID- 14966012
TI  - Stomatal and mesophyll limitations of photosynthesis in black spruce seedlings
      during multiple cycles of drought.
AB  - Container-grown black spruce (Picea mariana (Mill.) B.S.P.) seedlings were
      planted in trays containing a sand and peat mixture, and placed in a climate
      controlled greenhouse. One group of seedlings was kept well-watered, and another
      group was subjected to three cycles of drought. Gas exchange analysis showed that
      mesophyll photosynthetic function was largely unimpaired by drought. In contrast,
      stomatal conductance was sensitive to drought, although it became less sensitive
      with each drought cycle. Both stomatal and mesophyll conductances increased with
      time in control and drought-stressed seedlings, but mesophyll conductance
      increased with time more rapidly than did stomatal conductance. Limitation of
      photosynthetic rate was dominated by the mesophyll. In control seedlings,
      relative stomatal limitation increased from 6 to 16% by the end of the
      experiment. In drought-stressed seedlings, relative stomatal limitation of
      photosynthesis reached 40% during the first drought, but decreased to near
      control values immediately after rewatering. Because the third, most severe
      drought had only a minor effect on stomatal conductance, relative stomatal
      limitation of photosynthesis was similar to that in control seedlings by the end
      of the experiment. Inhibition of ontogenetic change during drought stress may be
      responsible for the apparent acclimation of mesophyll photosynthetic processes.
      We conclude that it would be more effective to select for high photosynthetic
      capacity than for reduced stomatal sensitivity when breeding for increased
      drought resistance in black spruce seedlings.

PMID- 14966013
TI  - Seasonal changes in the transient expression of a 35S CaMV-GUS gene construct
      introduced into Scots pine buds.
AB  - Seasonal changes in the transient expression of Beta-glucuronidase gene (GUS)
      driven by a constitutive 35S CaMV-promoter in Scots pine (Pinus sylvestris L.)
      buds were studied by the microprojectile DNA-delivery method. Buds were collected
      from 5-, 15- and 50-year-old trees. In buds from all age groups the amount of
      transient expression was dependent on the season; the highest values were found
      in March, and values were lowest both at the beginning and at the end of the
      growing season. Pretreatment with growth regulators increased both the amount of
      transient GUS expression and arginine decarboxylase (ADC) activity in buds
      indicating an increase in metabolic activity. These results confirm that the
      genetic transformation technique can be used to study seasonally dependent
      regulation in mature Scots pine tissues.

PMID- 14966014
TI  - Nasal cavity dimensions in guinea pig and rat measured by acoustic rhinometry and
      fluid-displacement method.
AB  - The purpose of the study was to measure nasal passageway dimensions in guinea
      pigs and rats by use of acoustic rhinometry (AR) and by a previously described
      fluid-displacement method (FDM) (Straszek SP, Taagehoej F, Graff S, and Pedersen
      OF. J Appl Physiol 95: 635-642, 2003) to investigate the potential of AR in
      pharmacological research with these animals. We measured the area-distance
      relationships by AR of nasal cavities postmortem in five guinea pigs (Duncan
      Hartley, 400 g) and five rats (Wistar, 250 g) by using custom-made equipment
      scaled for the purpose. Nosepieces were made from plastic pipette tips and either
      inserted into or glued onto the nostrils. We used liquid perfluorocarbon in the
      fluid-displacement study, and it was carried out subsequent to the acoustic
      measurements. We found for guinea pigs that AR measured a mean volume of 98 mm(3)
      (95-100 mm(3)) (mean and 95% confidence interval) of the first 2 cm of the
      cavity. FDM measured a mean volume of 146 mm(3) (117-175 mm(3)), meaning that AR
      only measured 70% (50-90) of the volume by FDM. For rats, the volume from 0 to 2
      cm was 58 mm(3) (55-61 mm(3)) by AR and 73 mm(3) (60-87 mm(3)) by FDM, resulting
      in AR only measuring 83% (66-100%) of volume by FDM (see Table 2). We conclude
      that absolute nasal cavity dimensions are underestimated by AR in guinea pigs and
      rats. This does not preclude that relative changes may be correctly measured. In
      vivo trials with AR using rats have not yet been published. The FDM is possibly
      the most accurate alternative to AR for measurements of the nasal cavity geometry
      in small laboratory animals, but it can only be used postmortem.

PMID- 14966015
TI  - Energetic cost of breathing, body composition, and pulmonary function in horses
      with recurrent airway obstruction.
AB  - This study was conducted to determine whether horses with naturally occurring,
      severe chronic recurrent airway obstruction (RAO) 1). have a greater resting
      energy expenditure (REE) than control horses, 2). suffer body mass depletion, and
      3). have significantly decreased REE after bronchodilation and, therefore, also
      4). whether increased work of breathing contributes to the cachexia seen in some
      horses with RAO. Six RAO horses and six control horses underwent indirect
      calorimetric measures of REE and pulmonary function testing using the esophageal
      balloon-pneumotachograph method before and after treatment with ipratropium
      bromide, a parasympatholytic bronchodilator agent, at 4-h intervals for a 24-h
      period. Body condition scoring was performed, and an estimate of fat mass was
      determined via B-mode ultrasonography. O(2) and CO(2) fractions, respiratory
      airflow, respiratory rate, and pleural pressure changes were recorded, and O(2)
      consumption, CO(2) production, REE, pulmonary resistance, dynamic elastance, and
      tidal volume were calculated. In addition, we performed lung function testing and
      calorimetry both before and after sedation in two control horses. RAO horses had
      significantly lower body condition scores (2.8 +/- 1.0 vs. 6.4 +/- 1.2) and
      significantly greater O(2) consumption than controls (4.93 +/- 1.30 vs. 2.93 +/-
      0.70 ml.kg(-1).min(-1)). After bronchodilation, there was no significant
      difference in O(2) consumption between RAO horses and controls, although there
      remained evidence of residual airway obstruction. There was a strong correlation
      between O(2) consumption and indexes of airway obstruction. Xylazine sedation was
      not associated with changes in pulmonary function but did result in markedly
      decreased REE in controls.

PMID- 14966016
TI  - Injections of recombinant human erythropoietin increases lactate influx into
      erythrocytes.
AB  - Previous studies showed that erythropoietin not only increases erythrocyte
      production but is also essential in both the synthesis and the good functioning
      of several erythrocyte membrane proteins, including band 3. It is still unknown
      whether anion and/or H(+) fluxes are modified by erythropoietin. This study aimed
      to evaluate the effect of recombinant human erythropoietin (rHuEPO) injections on
      lactate transport into erythrocytes via band 3 and H(+)-monocarboxylate
      transporter MCT-1, two proteins involved in lactate exchange. Nine athletes
      received subcutaneous rHuEPO (50 U/kg body mass 3 times a week for 4 wk), and
      seven athletes received a saline solution (placebo group). All subjects were also
      supplemented with oral iron and vitamins B(9) and B(12). Lactate transport into
      erythrocytes was studied before and after the rHuEPO treatment at different
      lactate concentrations (1.6, 8.1, 41, and 81.1 mM). After treatment, MCT-1
      lactate uptake was increased at 1.6, 41 (P < 0.01), and 81.1 mM lactate
      concentration (P < 0.001) although lactate uptake via band 3 and nonionic
      diffusion were unchanged. MCT-1 maximal velocity increased in the rHuEPO group (P
      < 0.05), reaching higher values than in the placebo group (P < 0.05) after
      treatment. Our results show that rHuEPO injections increased MCT-1 lactate influx
      at low and high lactate concentrations. The increase in MCT-1 maximal velocity
      suggests that rHuEPO may stimulate MCT-1 synthesis during erythrocyte formation
      in bone marrow.

PMID- 14966017
TI  - Effects of posture and bronchoconstriction on low-frequency input and transfer
      impedances in humans.
AB  - We simultaneously evaluated the mechanical response of the total respiratory
      system, lung, and chest wall to changes in posture and to bronchoconstriction. We
      synthesized the optimal ventilation waveform (OVW) approach, which simultaneously
      provides ventilation and multifrequency forcing, with optoelectronic
      plethysmography (OEP) to measure chest wall flow globally and locally. We applied
      an OVW containing six frequencies from 0.156 to 4.6 Hz to the mouth of six
      healthy men in the seated and supine positions, before and after methacholine
      challenge. We measured mouth, esophageal, and transpulmonary pressures, airway
      flow by pneumotachometry, and total chest wall, pulmonary rib cage, and abdominal
      volumes by OEP. We computed total respiratory, lung, and chest wall input
      impedances and the total and regional transfer impedances (Ztr). These data were
      appropriately sensitive to changes in posture, showing added resistance in supine
      vs. seated position. The Ztr were also highly sensitive to lung constriction,
      more so than input impedance, as the former is minimally distorted by shunting of
      flow into alveolar gas compression and airway walls. Local impedances show that,
      during bronchoconstriction and at typical breathing frequencies, the contribution
      of the abdomen becomes amplified relative to the rib cage. A similar
      redistribution occurs when passing from seated to supine. These data suggest that
      the OEP-OVW approach for measuring Ztr could noninvasively track important lung
      and respiratory conditions, even in subjects who cannot cooperate. Applications
      might range from routine evaluation of airway hyperreactivity in asthmatic
      subjects to critical conditions in the supine position during mechanical
      ventilation.

PMID- 14966018
TI  - Effect of tidal volume on distribution of ventilation assessed by synchrotron
      radiation CT in rabbit.
AB  - A respiration-gated synchrotron radiation computed tomography (SRCT) technique,
      which allows visualization and direct quantification of inhaled stable xenon gas,
      was used to study the effect of tidal volume (Vt) on regional lung ventilation.
      High-resolution maps (pixel size 0.35 x 0.35 mm) of local washin time constants
      (tau) and regional specific ventilation were obtained in five anesthetized,
      paralyzed, and mechanically ventilated rabbits in upright body position at the
      fourth, sixth, and eighth dorsal vertebral levels with a Vt from 4.9 +/- 0.3 to
      7.9 +/- 0.4 ml/kg (means +/- SE). Increasing Vt without an increase in minute
      ventilation resulted in a proportional increase of mean specific ventilation up
      to 65% in all studied lung levels and reduced the scattering of washin tau
      values. The tau values had log-normal distributions. The results indicate that an
      increase in Vt decreases nonuniformity of intraregional ventilatory gas exchange.
      The findings suggest that (SRCT) provides a new quantitative tool with high
      spatial discrimination ability for assessment of changes in peripheral pulmonary
      gas distribution during mechanical ventilation.

PMID- 14966019
TI  - Differential effects of ozone on airway and tissue mechanics in obese mice.
AB  - Obesity is an important risk factor for asthma. We recently reported increased
      ozone (O(3))-induced hyperresponsiveness to methacholine in obese mice (Shore SA,
      Rivera-Sanchez YM, Schwartzman IN, and Johnston RA. J Appl Physiol 95: 938-945,
      2003). The purpose of this study was to determine whether this increased
      hyperresponsiveness is the result of changes in the airways, the lung tissue, or
      both. To that end, we examined the effect of O(3) (2 parts/million for 3 h) on
      methacholine-induced changes in lung mechanics with the use of a forced
      oscillation technique in wild-type C57BL/6J mice and mice obese because of a
      genetic deficiency in leptin (ob/ob mice). In ob/ob mice, O(3) increased baseline
      values for all parameters measured in the study: airway resistance (Raw), lung
      tissue resistance (Rtis), lung tissue damping (G) and elastance (H), and lung
      hysteresivity (eta). In contrast, no effect of O(3) on baseline mechanics was
      observed in wild-type mice. O(3) exposure significantly increased Raw, Rtis, lung
      resistance (Rl), G, H, and eta responses to methacholine in both groups of mice.
      For G, Rtis, and Rl there was a significant effect of obesity on the response to
      O(3). Our results demonstrate that both airways and lung tissue contribute to the
      hyperresponsiveness that occurs after O(3) exposure in wild-type mice. Our
      results also demonstrate that changes in the lung tissue rather than the airways
      account for the amplification of O(3)-induced hyperresponsiveness observed in
      obese mice.

PMID- 14966020
TI  - Neural and mechanical responses of the triceps surae muscle group after 1 h of
      repeated fast passive stretches.
AB  - Experiments were carried out to examine interaction between mechanical changes of
      the muscle-tendon unit and reduced reflex sensitivity after repeated and
      prolonged passive muscle stretching (RPS). There is some evidence that this
      interaction might be relevant also during active stretch-shortening cycle type of
      fatigue tasks. The results demonstrated a clear deterioration of voluntarily and
      electrically induced muscle contractions after RPS. Maximal voluntary contraction
      (MVC), average electromyographic activities of the gastrocnemius and soleus
      muscles, and maximal twitch contraction decreased on average by 13.8, 10.4, 7.6,
      and 16.8%, respectively. In addition, there was a 14% lengthening in the total
      duration of the twitch. MVCs measured at different ankle joint angles revealed a
      downward and rightward shift in the torque-fascicle length curve after RPS.
      Interestingly, there was a crossing in the torque-fascicle length curves while
      measured at different activation levels but at the same joint angle before and
      after RPS. Even though no changes were observed in the activation level during
      MVCs, all the reflex parameters showed a clear reduction after RPS. This study
      presents evidence that repeated and prolonged passive muscle stretching can lead
      to some modification of material behavior of the aponeurosis-tendon system, such
      as stress relaxation and/or plastic deformation. In addition, altered material
      properties seem to affect proprioceptive feedback and, therefore, the motor unit
      activation in proportion to the contractile failure.

PMID- 14966021
TI  - Effect of caffeine on peripheral chemoreceptor activity in premature neonates:
      interaction with sleep stages.
AB  - Caffeine is widely used for the treatment of apnea in premature neonates.
      However, the localization of caffeine's target site (central nervous system
      and/or peripheral chemoreceptors) is not well defined, especially for sleeping
      neonates whose sleep stages interact with respiratory control. The aim of this
      study was to assess the activity of the peripheral chemoreceptors in relation to
      sleep stages in premature neonates treated (or not) with caffeine for idiopathic
      apnea. Peripheral chemoreceptor activity was assessed in 22 neonates
      (postconceptional age of 36 +/- 1 wk with birth weights ranging from 790 to 1,910
      g) by performing a 30-s hyperoxic test during active and quiet sleep. Eleven
      neonates received caffeine treatment (4.0 +/- 0.5 mg.kg(-1).day(-1)) and 11
      served as controls. For all neonates, the decrease in minute ventilation observed
      during hyperoxia was greater during active than during quiet sleep. Neonates
      receiving caffeine showed a significantly greater decrease in ventilation during
      hyperoxia in both sleep stages, compared with controls (caffeine; -29.7 +/- 12.8%
      vs. control; -22.0 +/- 7.4%; F(1,15) = 4.6, P = 0.04). We conclude that caffeine
      administration increases the effectiveness of chemoreceptor activity. Because
      sleep stage durations were not affected by the treatment, it is likely that the
      decrease in apneic episodes typically observed with caffeine therapy is only
      related to respiratory processes and is independent of the sleep stage
      organization.

PMID- 14966022
TI  - Modeled microgravity-induced protein kinase C isoform expression in human
      lymphocytes.
AB  - In long-term space travel, the crew is exposed to microgravity and radiation that
      invoke potential hazards to the immune system. T cell activation is a critical
      step in the immune response. Receptor-mediated signaling is inhibited in both
      microgravity and modeled microgravity (MMG) as reflected by diminished DNA
      synthesis in peripheral blood lymphocytes and their locomotion through gelled
      type I collagen. Direct activation of protein kinase C (PKC) bypassing cell
      surface events using the phorbol ester PMA rescues MMG-inhibited lymphocyte
      activation and locomotion, whereas the calcium ionophore ionomycin had no rescue
      effect. Thus calcium-independent PKC isoforms may be affected in MMG-induced
      locomotion inhibition and rescue. Both calcium-dependent isoforms and calcium
      independent PKC isoforms were investigated to assess their expression in
      lymphocytes in 1 g and MMG culture. Human lymphocytes were cultured and harvested
      at 24, 48, 72, and 96 h, and serial samples were assessed for locomotion by using
      type I collagen and expression of PKC isoforms. Expression of PKC-alpha, -delta,
      and -epsilon was assessed by RT-PCR, flow cytometry, and immunoblotting. Results
      indicated that PKC isoforms delta and epsilon were downregulated by >50% at the
      transcriptional and translational levels in MMG-cultured lymphocytes compared
      with 1-g controls. Events upstream of PKC, such as phosphorylation of
      phospholipase Cgamma in MMG, revealed accumulation of inactive enzyme. Depressed
      calcium-independent PKC isoforms may be a consequence of an upstream lesion in
      the signal transduction pathway. The differential response among calcium
      dependent and calcium-independent isoforms may actually result from MMG intrusion
      events earlier than PKC, but after ligand-receptor interaction.

PMID- 14966023
TI  - Anatomic capillarization is maintained in relative excess of fiber oxidative
      capacity in some skeletal muscles of late middle-aged rats.
AB  - The anatomic size of the capillary-to-fiber (C/F) interface plays an important
      role in O(2) flux from blood to tissue by determining the surface area available
      for diffusion and is maintained in relative proportion to fiber mitochondrial
      volume across a wide range of muscle aerobic capacity. In the present study, we
      examined an estimate of the anatomic size of the C/F interface [the quotient of
      the individual C/F ratio and fiber perimeter, C/F perimeter exchange (CFPE)
      index] and fiber oxidative capacity in different skeletal muscles, or muscle
      regions, to test the hypothesis that capillarization would be maintained in
      relative excess of reduced fiber oxidative capacity in aged muscles. The right
      gastrocnemius, plantaris, and soleus muscles from young adult (8 mo old) and late
      middle-aged (28-30 mo old) Fischer 344 x Brown Norway F1 hybrid rats were excised
      for evaluation of flux through electron transport chain complexes I-III and/or
      morphometric estimation of capillarization. Muscle mass was lower in the
      gastrocnemius muscles of the older animals (2,076 +/- 32 vs. 1,825 +/- 47 mg in
      young adult vs. late middle-aged, respectively; mean +/- SE) but not the
      plantaris or soleus muscles. Fibers were smaller in the white region of
      gastrocnemius muscles but larger in the red region of gastrocnemius muscles of
      the older animals. There was no difference in the number of capillaries around a
      fiber, the individual C/F ratio, or the CFPE index between groups for any
      muscle/region, whereas flux through complexes I-III was reduced by 29-43% in late
      middle-aged animals. Thus the greater quotient of indexes of anatomic capillarity
      (individual C/F ratio or CFPE index) and fiber oxidative capacity in soleus and
      the white region of gastrocnemius muscles, but not in the red region of
      gastrocnemius muscles of the older animals, shows that anatomic capillarity is
      maintained in relative excess of oxidative capacity in some muscle regions in
      late middle-aged rats.

PMID- 14966024
TI  - Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle
      during fasting.
AB  - Fasting forces adaptive changes in whole body and skeletal muscle metabolism that
      increase fat oxidation and decrease the oxidation of carbohydrate. We tested the
      hypothesis that 40 h of fasting would decrease pyruvate dehydrogenase (PDH)
      activity and increase PDH kinase (PDK) isoform mRNA expression in human skeletal
      muscle. The putative transcriptional activators of PDK isozymes, peroxisome
      proliferator-activated receptor-alpha (PPAR-alpha) protein, and forkhead homolog
      in rhabdomyosarcoma (FKHR) mRNA were also measured. Eleven healthy adults fasted
      after a standard meal (25% fat, 60% carbohydrate, 15% protein) with blood and
      skeletal muscle samples taken at 3, 15, and 40 h postprandial. Fasting increased
      plasma free fatty acid, glycerol, and beta-hydroxybutyrate concentrations and
      decreased glucose and insulin concentrations. PDH activity decreased from 0.88 +/
      0.11 mmol acetyl-CoA. min(-1). kg wet muscle wt(-1) at 3 h to 0.62 +/- 0.10 (P =
      not significant) and 0.39 +/- 0.06 (P < 0.05) mmol. min(-1). kg wet mass(-1)
      after 15 and 40 h of fasting. Although all four PDK isoforms were expressed in
      human skeletal muscle, PDK-2 and -4 mRNA were the most abundant. PDK-1 and -3
      mRNA abundance was approximately 1 and 15% of the PDK-2 and -4 levels,
      respectively. The 40-h fast had no effect on PDK-1, -2, and -3 mRNA expression.
      PDK-4 mRNA was significantly increased approximately 3-fold after 15 h and
      approximately 14-fold after 40 h of fasting. Skeletal muscle PPAR-alpha protein
      and FKHR mRNA abundance were unaffected by the fast. The results suggest that
      decreased PDH activation after 40 h of fasting may have been a function of the
      large increase in PDK-4 mRNA expression and possible subsequent increase in PDK
      protein and activity. The changes in PDK-4 expression and PDH activity did not
      coincide with increases in the transcriptional activators PPAR-alpha and FKHR.

PMID- 14966025
TI  - Men are more fatigable than strength-matched women when performing intermittent
      submaximal contractions.
AB  - The purpose of this study was to compare the time to task failure for a series of
      intermittent submaximal contractions performed with the elbow flexor muscles by
      men and women who were matched for strength (n = 20, 18-34 yr). The fatigue task
      comprised isometric contractions at 50% of maximal voluntary contraction (MVC)
      torque (6-s contraction, 4-s rest). The MVC torque was similar for the men and
      women [64.8 +/- 9.2 (SD) vs. 62.2 +/- 7.9 N.m; P > 0.05]. However, the time to
      task failure was longer for the women (1,408 +/- 1,133 vs. 513 +/- 194 s; P <
      0.05), despite the similar torque levels. The mean arterial pressure, heart rate,
      and rating of perceived exertion started and ended at similar values for the men
      and women, but the rate of increase was less for the women. The rate of increase
      in the average of the rectified electromyogram (AEMG; % peak MVC) for the elbow
      flexor muscles was less for the women: the AEMG was greater for the men compared
      with the women at task failure (72 +/- 28 vs. 50 +/- 21%; P < 0.05), despite
      similar AEMG values at the start of the fatiguing contraction (32 +/- 9 vs. 36 +/
      13%). These results indicate that for intermittent contractions performed with
      the elbow flexor muscles 1) the sex difference in time to task failure was not
      explained by the absolute strength of the men and women, but involved another
      mechanism that is present during perfused conditions, and 2) men required a more
      rapid increase in descending drive to maintain a similar torque.

PMID- 14966026
TI  - Hibernating myocardium: high or low risk?

PMID- 14966027
TI  - Severe valvar aortic stenosis in a child with familial hypercholesterolaemia.

PMID- 14966028
TI  - Atrial fibrillation: an emerging epidemic?

PMID- 14966029
TI  - Implantable cardioverter-defibrillators for children and young adolescents:
      mortality benefit confirmed--what's next?

PMID- 14966030
TI  - Acute incomplete thrombotic occlusion of distal left main coronary artery treated
      by tissue plasminogen activator.

PMID- 14966031
TI  - The MADIT II and COMPANION studies: will they affect uptake of device treatment?

PMID- 14966032
TI  - Balloon dilation of the stenotic fifth aortic arch in a newborn with double lumen
      aortic arch.

PMID- 14966033
TI  - Recent insights into human coronary collateral development.
AB  - Enhancement of coronary collateral function is an intriguing approach to the
      preservation of ischaemic myocardium. Coronary collateral development consists of
      collateral recruitment and collateral growth. Collateral growth encompasses
      proliferation of capillaries in the ischaemic area (angiogenesis) and maturation
      of pre-existing collateral vessels (arteriogenesis), with the latter being more
      relevant in humans. Therefore, treatment intended directly for arteriogenesis of
      collateral vessels appears to be more effective. Promotion of coronary collateral
      growth has many attractive features, particularly in patients with angina who are
      not indicated for percutaneous coronary intervention or coronary artery bypass
      grafting surgery. A complete elucidation of the remaining practical and
      mechanistic questions of arteriogenesis may lead to a new remedy capable of
      developing collateral vessels more effectively.

PMID- 14966034
TI  - Deep vein thrombosis demonstrated by contrast enhanced helical computed
      tomographic venography.

PMID- 14966036
TI  - Acute pericardial disease: approach to the aetiologic diagnosis.

PMID- 14966037
TI  - Aortic intramural haematoma leading to aortic dissection.

PMID- 14966038
TI  - Pericardial effusion: haemodynamic spectrum.

PMID- 14966039
TI  - Pericardial constriction: uncommon patterns.

PMID- 14966040
TI  - Risk factors for non-fatal myocardial infarction in young South Asian adults.
AB  - OBJECTIVE: To determine the risk factors for premature myocardial infarction
      among young South Asians. DESIGN AND SETTING: Case-control study in a hospital
      admitting unselected patients with non-fatal acute myocardial infarction. METHODS
      AND SUBJECTS: Risk factor assessment was done in 193 subjects aged 15-45 years
      with a first acute myocardial infarct, and in 193 age, sex, and neighbourhood
      matched population based controls. RESULTS: The mean (SD) age of the subjects was
      39 (4.9) years and 326 (84.5%) were male. Current smoking (odds ratio (OR) 3.82,
      95% confidence interval (CI) 1.47 to 9.94), use of ghee (hydrogenated vegetable
      oil) in cooking (OR 3.91, 95% CI 1.52 to 10.03), raised fasting blood glucose (OR
      3.32, 95% CI 1.21 to 8.62), raised serum cholesterol (OR 1.67, 95% CI 1.14 to
      2.45 for each 1.0 mmol/l increase), low income (OR 5.05, 95% CI 1.71 to 14.96),
      paternal history of cardiovascular disease (OR 4.84, 95% CI 1.42 to 16.53), and
      parental consanguinity (OR 3.80, 95% CI 1.13 to 1.75) were all independent risk
      factors for acute myocardial infarction in young adults. Formal education versus
      no education had an independently protective effect on acute myocardial
      infarction (OR 0.04, 95% CI 0.01 to 0.35). CONCLUSIONS: Tobacco use, ghee intake,
      raised fasting glucose, high cholesterol, paternal history of cardiovascular
      disease, low income, and low level of education are associated with premature
      acute myocardial infarction in South Asians. The association of parental
      consanguinity with acute myocardial infarction is reported for the first time and
      deserves further study.

PMID- 14966041
TI  - Prognostic relations between inflammatory markers and mortality in diabetic
      patients with non-ST elevation acute coronary syndrome.
AB  - OBJECTIVE: To determine the differences in the inflammatory status between
      diabetic and non-diabetic patients and to evaluate the usefulness of C reactive
      protein, fibrinogen, and leucocyte count as predictors of death in diabetic
      patients with unstable coronary disease. DESIGN: Nested case-control comparisons
      of the inflammatory status between diabetic and non-diabetic patients.
      Prospective cohort analysis of C reactive protein concentration, fibrinogen
      concentration, and leucocyte count as predictors of cardiovascular death in
      diabetic patients. SETTING: Coronary care unit in Spain. PARTICIPANTS: 83
      diabetic patients with non-ST elevation acute coronary syndrome and 83 sex and
      aged matched patients selected from 361 non-diabetic patients with non-ST
      elevation acute coronary syndrome. MAIN OUTCOME MEASURES: Plasma concentrations
      of C reactive protein and fibrinogen, and leucocyte count. Investigators
      contacted patients to assess clinical events. RESULTS: Concentrations of C
      reactive protein and fibrinogen, and leucocyte count on admission were higher in
      diabetic than in non-diabetic patients (7 mg/l v 5 mg/l, p = 0.020; 3.34 g/l v
      2.90 g/l, p = 0.013; and 8.8 x 10(9)/l v 7.8 x 10(9)/l, p = 0.040). Among
      diabetic patients, these values were also higher in those who died during the 22
      month follow up (13 mg/l v 6 mg/l, p = 0.001; 3.95 g/l v 3.05 g/l, p < 0.001; and
      11.4 x 10(9)/l v 8.4 x 10(9)/l, p = 0.005). After adjustment for confounding
      factors, diabetic patients in the highest tertile of C reactive protein had a
      hazard ratio for cardiovascular death of 4.51 (95% confidence interval (CI) 1.62
      to 12.55). Similar hazard ratios were for fibrinogen 3.74 (95% CI 1.32 to 10.62)
      and for leucocyte count 3.64 (95% CI 1.37 to 9.68). CONCLUSIONS: Inflammation
      appears more evident in diabetic than in non-diabetic patients with acute
      coronary syndrome. C reactive protein concentration, fibrinogen concentration,
      and leucocyte count constitute independent predictors of cardiovascular death in
      diabetics with unstable coronary disease.

PMID- 14966044
TI  - Pericardial constriction after a stab wound to the chest.

PMID- 14966043
TI  - Insulin induced increase in coronary flow reserve is abolished by dexamethasone
      in young men with uncomplicated type 1 diabetes.
AB  - OBJECTIVE: To examine the role of the sympathetic nervous system in regulating
      insulin's action on coronary perfusion in uncomplicated type 1 diabetes by
      blocking centrally mediated sympathetic activity with dexamethasone. METHODS:
      Positron emission tomography and oxygen 15 labelled water were used to quantify
      myocardial blood flow basally and during adenosine infusion with or without
      simultaneous euglycaemic physiological hyperinsulinaemia in nine non-smoking men
      with type 1 diabetes and 12 healthy non-diabetic men. Each patient was studied
      both with and without previous dexamethasone treatment for two days (2 mg/day).
      RESULTS: Insulin increased coronary flow reserve in diabetic (from 4.3 (0.7) to
      5.1 (0.6), p < 0.05) and non-diabetic (from 4.3 (0.3) to 5.4 (0.4), p < 0.05)
      patients. In contrast to non-diabetic patients dexamethasone pretreatment
      abolished the insulin induced increase in coronary flow reserve in diabetic
      patients (p < 0.05) leading to lower coronary flow reserve in diabetic than in
      non-diabetic patients (3.9 (0.6) v 7.1 (0.9), p < 0.05). CONCLUSIONS: These
      results show that insulin's ability to modulate coronary perfusion is sustained
      in young patients with type 1 diabetes without microvascular complications or
      autonomic neuropathy. Dexamethasone treatment abolished the insulin induced
      increase in coronary flow reserve in diabetic patients but not in healthy study
      participants, suggesting that sympathetic activation plays an important part in
      regulating insulin's effects on myocardial perfusion in patients with type 1
      diabetes.

PMID- 14966045
TI  - Sex differences in the expression of haemorheological determinants in individuals
      with atherothrombotic risk factors and in apparently healthy people.
AB  - BACKGROUND: Increased red cell aggregation can be detrimental, leading to slow
      capillary blood flow and tissue hypoxaemia. Sex differences in the degree of
      erythrocyte adhesiveness/aggregation in the peripheral blood have not been
      clearly shown. OBJECTIVES: To determine whether there are sex differences in the
      expression of erythrocyte adhesiveness/aggregation in the peripheral blood in
      individuals with atherothrombotic risk factors and in apparently healthy people.
      METHODS: From a cohort of 965 participants in the Tel Aviv Medical Centre
      inflammation survey, 192 pairs of different sex were matched for age, body mass
      index, hip and waist circumferences, cardiovascular risk factors, and the intake
      of active cardiovascular drugs. RESULTS: Women had an enhanced degree of red cell
      aggregation (p < 0.0005) as well as increased concentrations of inflammation
      sensitive proteins including fibrinogen and C reactive protein. Women had a lower
      haemoglobin concentration than men, but this did not affect the degree of
      erythrocyte adhesiveness/aggregation. CONCLUSIONS: The significant increase in
      red blood cell adhesiveness/aggregation in the peripheral blood of women with
      atherothrombosis could be relevant to the more eventful course that some women
      experience during and following acute ischaemic disease.

PMID- 14966046
TI  - Non-compaction of the left ventricle.

PMID- 14966047
TI  - Association of endothelial constitutive nitric oxide synthase gene polymorphism
      with acute coronary syndrome in Koreans.
AB  - OBJECTIVE: To examine the effects of two polymorphisms of the endothelial
      constitutive nitric oxide synthase (ecNOS) gene, 4a/4b(A:B) located in intron 4
      and Glu298Asp(G:T) located in exon 7, on the development of acute coronary
      syndromes (ACS). METHODS: 164 patients with ACS and 142 control participants were
      investigated for genotype and conventional risk factors. Genotype was determined
      by polymerase chain reaction and restriction fragment length polymorphism
      analysis. RESULTS: Genotype and allele frequencies of the A:B polymorphism in the
      ACS group (0.15:0.85 for AA+AB:BB, 0.09:0.91 for A:B) differed from those in the
      control group (0.26:0.74 for AA+AB:BB, 0.15:0.85 for A:B). However, genotype and
      allele frequencies of the G:T polymorphism in the ACS group (0.22:0.78 for
      TT+TG:GG, 0.11:0.89 for T:G) were similar to those in the control group
      (0.17:0.83 for TT+TG:GG, 0.09:0.91 for T:G). Multiple logistic regression
      analysis showed that the non-BB (AA+AB) and the non-BB+GG genotypes were
      significant protective factors against ACS (odds ratios 0.49 and 0.34, 95%
      confidence intervals 0.26 to 0.93 and 0.14 to 0.83, respectively). In addition,
      linear association analysis showed that the percentage of ACS patients was
      significantly lower in the genotype group non-BB+GG than in the genotype group
      BB+non-GG (39.6% v 62.7%, p = 0.01). CONCLUSIONS: The non-BB genotype of the
      ecNOS 4a/4b gene polymorphism is a protective factor against the development of
      ACS. The GG genotype of the ecNOS Glu298Asp polymorphism exerts a benefit in
      addition to the non-BB genotype in the Korean population.

PMID- 14966048
TI  - Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the
      UK.
AB  - OBJECTIVE: To evaluate the cost of atrial fibrillation (AF) to health and social
      services in the UK in 1995 and, based on epidemiological trends, to project this
      estimate to 2000. DESIGN, SETTING, AND MAIN OUTCOME MEASURES: Contemporary
      estimates of health care activity related to AF were applied to the whole
      population of the UK on an age and sex specific basis for the year 1995. The
      activities considered (and costs calculated) were hospital admissions, outpatient
      consultations, general practice consultations, and drug treatment (including the
      cost of monitoring anticoagulant treatment). By adjusting for the progressive
      aging of the British population and related increases in hospital admissions, the
      cost of AF was also projected to the year 2000. RESULTS: There were 534 000
      people with AF in the UK during 1995. The "direct" cost of health care for these
      patients was 244 million pounds sterling (approximately 350 million euros) or
      0.62% of total National Health Service (NHS) expenditure. Hospitalisations and
      drug prescriptions accounted for 50% and 20% of this expenditure, respectively.
      Long term nursing home care after hospital admission cost an additional 46.4
      million pounds sterling (approximately 66 million euros). The direct cost of AF
      rose to 459 million pounds sterling (approximately 655 million euros) in 2000,
      equivalent to 0.97% of total NHS expenditure based on 1995 figures. Nursing home
      costs rose to 111 million pounds sterling (approximately 160 million euros).
      CONCLUSIONS: AF is an extremely costly public health problem.

PMID- 14966049
TI  - Massive aortic aneurysm presenting as chest wall swelling.

PMID- 14966050
TI  - Relation between left ventricular contractile reserve during low dose dobutamine
      echocardiography and plasma concentrations of natriuretic peptides.
AB  - BACKGROUND: In ischaemic cardiomyopathy, raised plasma concentrations of
      natriuretic peptides are associated with a poor long term prognosis, while the
      presence of contractile reserve is a favourable sign. OBJECTIVE: To assess the
      relation between plasma natriuretic peptides and contractile reserve. DESIGN:
      Prospective observational study. SETTING: Tertiary referral centre. PATIENTS: 66
      consecutive patients undergoing low dose dobutamine stress echocardiography to
      evaluate contractile reserve in regions with contractile dysfunction at rest,
      divided into two groups: group 1, 31 patients with ischaemic cardiomyopathy (left
      ventricular ejection fraction < or = 40%) and heart failure symptoms; group 2, 35
      patients with normal left ventricular function. MAIN OUTCOME MEASURES: Plasma
      atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), measured
      using immunoradiometric assays. Contractile reserve was defined as an improvement
      in segmental wall motion score during infusion of low dose dobutamine. RESULTS:
      Plasma ANP and BNP concentrations were higher in group 1 than in group 2 (mean
      (SD): ANP, 17.8 (32.8) v 7.2 (9.7), p < 0.005; BNP, 24.4 (69.0) v 5.0 (14.3)
      pmol/l, respectively; p < 0.001). In group 1, the presence of contractile reserve
      was inversely related to ANP and BNP levels; however, patients with contractile
      reserve had lower ANP and BNP concentrations than patients without contractile
      reserve (ANP, 14.2 (9.1) v 24.2 (44.2), p < 0.05; BNP, 20.2 (25.5) v 37.5 (93.8)
      pmol/l, respectively; p < 0.05). CONCLUSIONS: Plasma natriuretic peptide
      concentrations are raised in patients with left ventricular dysfunction, but in
      the presence of preserved myocardial contractile reserve, relatively low levels
      of ANP and BNP are present.

PMID- 14966051
TI  - Dynamic respiratory changes in hypertrophic cardiomyopathy.

PMID- 14966053
TI  - Aortic valve endocarditis causing fatal myocardial infarction caused by ostial
      coronary artery obliteration.

PMID- 14966052
TI  - Diagnostic and prognostic evaluation of left ventricular systolic heart failure
      by plasma N-terminal pro-brain natriuretic peptide concentrations in a large
      sample of the general population.
AB  - OBJECTIVE: To evaluate N-terminal pro-brain natriuretic peptide (NT-proBNP) as a
      diagnostic and prognostic marker for systolic heart failure in the general
      population. DESIGN: Study participants, randomly selected to be representative of
      the background population, filled in a heart failure questionnaire and underwent
      pulse and blood pressure measurements, electrocardiography, echocardiography, and
      blood sampling and were followed up for a median (range) period of 805 (60-1171)
      days. SETTING: Participants were recruited from four randomly selected general
      practitioners and were examined in a Copenhagen university hospital. PATIENTS:
      382 women and 290 men in four age groups (50-59 (n = 174); 60-69 (n = 204); 70-79
      (n = 174); > or = 80 years (n = 120)). MAIN OUTCOME MEASURES: Value of NT-proBNP
      in evaluating patients with symptoms of heart failure and impaired left
      ventricular (LV) systolic function; prognostic value of NT-proBNP for mortality
      and hospital admissions. RESULTS: In 38 (5.6%) participants LV ejection fraction
      (LVEF) was < or = 40%. NT-proBNP identified patients with symptoms of heart
      failure and LVEF < or = 40% with a sensitivity of 0.92, a specificity of 0.86,
      positive and negative predictive values of 0.11 and 1.00, and area under the
      curve of 0.94. NT-proBNP was the strongest independent predictor of mortality
      (hazard ratio (HR) = 5.70, p < 0.0001), hospital admissions for heart failure (HR
      = 13.83, p < 0.0001), and other cardiac admissions (HR = 3.69, p < 0.0001).
      Mortality (26 v 6, p = 0.0003), heart failure admissions (18 v 2, p = 0.0002),
      and admissions for other cardiac causes (44 v 13, p < 0.0001) were significantly
      higher in patients with NT-proBNP above the study median (32.5 pmol/l).
      CONCLUSIONS: Measurement of NT-proBNP may be useful as a screening tool for
      systolic heart failure in the general population.

PMID- 14966054
TI  - Haemochromatosis gene mutations and risk of coronary heart disease: a west of
      Scotland coronary prevention study (WOSCOPS) substudy.
AB  - OBJECTIVES: To measure the frequency of genotypes of the HFE (haemochromatosis)
      gene in patients recruited to the west of Scotland coronary prevention study
      (WOSCOPS), and relate them to the subsequent occurrence of coronary clinical
      events. DESIGN: Nested case-control study, drawing samples of DNA from the
      biological bank of a cohort study. PATIENTS: Men aged 45-64 years in 1989, with
      moderate hypercholesterolaemia and no evidence of coronary heart disease at
      baseline. INTERVENTIONS: Follow up for a mean period of 4.9 years. Typing for
      C282Y and H63D mutations of the HFE gene in 482 subjects with a subsequent
      coronary event and 1104 without an event. RESULTS: The C282Y mutation was present
      in 81 of 482 cases (16.8%) and 182 of 1104 controls (16.5%). Comparing the
      prevalence of gene mutations in the cases and controls, there were no significant
      differences. The hazard ratio for C282Y heterozygotes was 1.03 (95% confidence
      interval (CI) 0.77 to 1.36) and for C282Y/H63D compound heterozygotes 1.04 (95%
      CI 0.50 to 2.14). Prespecified subgroup analyses of the pravastatin, placebo,
      smoking, and non-smoking groups showed no significant differences between cases
      and controls. Repeating the analyses after adjusting for possible confounding
      factors produced no change in the results. CONCLUSIONS: In a population of
      moderately hypercholesterolaemic middle aged Scottish men who did not have any
      evidence of coronary heart disease at baseline, the presence of a C282Y mutation
      in the HFE gene did not predict the occurrence of coronary events over a mean
      follow up of 4.9 years.

PMID- 14966055
TI  - Long term outcome up to 30 years after the Mustard or Senning operation: a
      nationwide multicentre study in Belgium.
AB  - OBJECTIVE: To assess long term outcome of patients who underwent Mustard or
      Senning repair for transposition of the great arteries up to 30 years earlier.
      DESIGN: Retrospective review of medical records. SETTING: The six university
      hospitals in Belgium with paediatric cardiology departments. PATIENTS: 339
      patients were reviewed, of whom 124 underwent the Mustard procedure and 215 the
      Senning procedure. This represents almost the entire population of patients in
      Belgium with either simple or complex transposition. MAIN OUTCOME MEASURES:
      Mortality, morbidity, functional abilities, social integration. RESULTS: Overall
      mortality was 24.2%. Early mortality (< or = 30 days after surgery) accounted for
      16.5%, late mortality for 7.7%. Actuarial survival of early survivors at 10, 20,
      and 30 years after surgery was 91.7%, 88.6%, and 79.3%, respectively. Patients in
      the Senning cohort had a slightly better survival rate than those in the Mustard
      cohort (NS). Baffle obstruction occurred more often after Mustard repair (15.3%)
      than after the Senning procedure (1.4%). Arrhythmia-free survival did not differ
      between the two cohorts, but was determined by the complexity of the
      transposition. Survivors of the Senning cohort had better functional status, and
      tended to engage in more sports activities. CONCLUSIONS: The long term outcome
      for patients surviving the Mustard or Senning operation was favourable in terms
      of late mortality, morbidity, functional, and social status. Overall mortality in
      the Senning cohort did not differ from the Mustard group, but Senning patients
      had better functional status, greater participation in sports activities, and
      fewer baffle related problems.

PMID- 14966057
TI  - Aortic pressure-area relation in Marfan patients with and without beta blocking
      agents: a new non-invasive approach.
AB  - OBJECTIVE: To investigate the heterogeneous response to beta blockade in patients
      with Marfan syndrome by non-invasive assessment of the aortic pressure-area
      curve. DESIGN AND PATIENTS: 25 patients with the Marfan syndrome who used beta
      blocking agents (mean (SD) age, 29 (10) years; 20 men, five women), seven without
      beta blockade (34 (14) years; five men, two women), and 10 controls (29 (5)
      years; seven men, three women) underwent magnetic resonance imaging and non
      invasive continuous blood pressure measurement. Pressure-area curves were
      constructed at the level of the descending thoracic aorta. A transition point was
      defined as the pressure at which the pressure-area relation deviated from its
      elastic (linear) to the collagen (exponential) course. SETTING: Tertiary referral
      centre for adult congenital heart disease. RESULTS: In six patients (five with
      and one without beta blockade), a transition point in the pressure-area curve was
      observed, indicating that the load bearing component was not only elastin but
      also collagen. In the remaining 26 Marfan patients and in the control subjects a
      linear pressure-area relation was observed. CONCLUSIONS: This new non-invasive
      method to derive aortic pressure-area curves showed that most patients with
      Marfan syndrome have a similar pressure-area curve to controls with similar blood
      pressures. Five patients on beta blockade showed a transition point in the
      pressure-area curve which could play a crucial role in the heterogeneous response
      to beta blocker treatment in Marfan patients. Patients with a transition at low
      blood pressures may not benefit from beta blocking agents.

PMID- 14966058
TI  - Aberrant tendinous chords with tethering of the tricuspid leaflets: a congenital
      anomaly causing severe tricuspid regurgitation.
AB  - OBJECTIVE: To define the entity of tricuspid regurgitation caused by tethering of
      the tricuspid valve leaflets by aberrant tendinous chords. DESIGN: Retrospective
      study. SETTING: Tertiary care centre (university teaching hospital). PATIENTS: 10
      patients with unexplained severe tricuspid regurgitation. METHODS: The last 13
      500 echocardiographic studies from our facility were reviewed to identify
      patients with severe unexplained tricuspid regurgitation. Tethering was defined
      by the presence of aberrant tendinous chords to the tricuspid valve leaflets
      limiting the mobility of the tricuspid leaflet and resulting in incomplete
      coaptation and apical displacement of the regurgitant jet origin. Aberrant
      tendinous chords were defined as those inserting at the clear zone of the
      tricuspid leaflet and not originating from the papillary muscle. Patients
      fulfilling the diagnostic criteria for Ebstein's anomaly were excluded. RESULTS:
      10 patients with aberrant tendinous chords tethering one or more tricuspid valve
      leaflets were identified. There were short non-aberrant tendinous chords in seven
      patients, five of whom also had right ventricular or tricuspid annulus
      dilatation. CONCLUSIONS: Tethering of the tricuspid valve leaflets by aberrant
      tendinous chords can be the sole mechanism of congenital tricuspid regurgitation.
      It is often associated with short non-aberrant tendinous chords, which may
      develop secondary to right ventricular or tricuspid annulus dilatation. Awareness
      of tethering as a cause of tricuspid regurgitation may be important in planning
      reconstructive surgery.

PMID- 14966060
TI  - Response of very small (2 mm) porcine coronary arteries to balloon angioplasty
      and stent implantation.
AB  - OBJECTIVE: To investigate the response of very small coronary arteries to stent
      deployment and balloon angioplasty. SETTING: Normal porcine coronary arteries.
      METHODS: 24 pigs underwent intervention to two main coronary arteries, in
      segments 2.0 mm in diameter, with balloons whose diameter was 2.5 mm at standard
      pressure. Twelve arteries received a BiodivYsio small vessel (SV) stent; 12 an
      NIR SV stent; 12 standard BiodivYsio stent, and 12 balloon only. The arteries
      were harvested at 28 days, fixed, embedded in plastic, and cut and ground in
      cross section. The injury score and histomorphometry were assessed. RESULTS: The
      BiodivYsio SV stent was associated with 20% less injury (p = 0.16), a 30% larger
      lumen (p = 0.13), and a 25% smaller neointima (p = 0.03) than the NIR SV stent,
      despite identical oversize. The standard BiodivYsio stent exhibited less recoil
      but 29% greater injury (p = 0.01), 59% more neointima (p = 0.00), and 18% less
      lumen (p = 0.27) than the BiodivYsio SV. Of all interventions, balloon only was
      associated with little injury, little neointima, major vessel shrinkage, and the
      largest lumen. CONCLUSION: Despite uniform oversize dilatation, both injury and
      response varied widely in very small porcine coronary arteries, depending on
      whether a stent or balloon was used, the stent design, and the number and/or
      thickness of struts. The response to different stent designs is considerable and
      is related to the degree of injury.

PMID- 14966061
TI  - Potential benefit from implantable cardioverter-defibrillator therapy in children
      and young adolescents.

PMID- 14966063
TI  - A 17 year experience of inappropriate shock therapy in patients with implantable
      cardioverter-defibrillators: are we getting any better?

PMID- 14966064
TI  - Transvenous low energy internal cardioversion for atrial fibrillation refractory
      to external cardioversion: do non-obese patients benefit?

PMID- 14966065
TI  - Amplatzer device closure of atrial septal defects in mature adults: analysis of
      76 cases.

PMID- 14966066
TI  - Diabetes and atherogenesis.

PMID- 14966067
TI  - Multi-vessel coronary disease and percutaneous coronary intervention.

PMID- 14966068
TI  - Clinical relevance of arrhythmias during sleep: guidance for clinicians.

PMID- 14966071
TI  - Massive cardiac involvement in acute lymphatic leukemia.

PMID- 14966072
TI  - Congenital coronary artery anomaly simulating an acute aortic dissection.
AB  - In this rare case, a patient had an anomalous right coronary artery originating
      from the left sinus of Valsalva coursing between the great vessels. He presented
      with symptoms and computed tomograms suggestive of an acute aortic dissection.

PMID- 14966073
TI  - Acute myocardial infarction probably caused by paradoxical embolus in a pregnant
      woman.
AB  - A 19 year old pregnant woman presented to the coronary care unit with an acute
      anterior myocardial infarction. She was treated with primary percutaneous
      transluminal coronary angioplasty of the proximal left anterior descending
      coronary artery. Ultrasound examination showed patent foramen ovale (PFO) and
      atrial septal aneurysm. The patient was a heterozygote carrier of factor V
      Leiden. Despite the lack of a clear clue, it was considered that the
      pathophysiological cause of this infarction was a paradoxical embolus in the left
      coronary artery. Pregnancy and factor V Leiden carriership are associated with
      increased risk of venous thromboembolism and the association between PFO and
      atrial septal aneurysm is a strong risk factor for systemic embolisation.

PMID- 14966074
TI  - Evidence for "lumen sealing" with sirolimus eluting stents in the treatment of
      complex coronary artery dissection.
AB  - Immediate and two month angiographic and intravascular ultrasound examination of
      sirolimus eluting stents deployed for complex coronary dissection is presented.
      The findings support the hypothesis that this novel treatment option is both
      effective and safe.

PMID- 14966075
TI  - Clopidogrel induced urticarial rash in a patient with left main stem percutaneous
      coronary intervention: management issues.
AB  - Clopidogrel, an ideal treatment for prevention of subacute stent thrombosis, may
      not be feasible to use in every patient. Ticlopidine (plus aspirin) is a very
      good alternative, although the risks of life threatening neutropenia should
      mandate regular monitoring of blood counts. It is proposed that patients
      undergoing angioplasty and stenting should carry a warning card in an effort to
      make the public and general practitioners aware that antiplatelet treatment after
      angioplasty plays an important part in ensuring successful outcome.

PMID- 14966076
TI  - Massive pulmonary haemorrhage complicating the treatment of acute coronary
      syndrome.
AB  - Antiplatelet medications such as clopidogrel and tirofiban (glycoprotien IIb/IIIa
      inhibitors) are associated with a reduction in mortality and morbidity and are
      therefore recommended in the treatment of acute coronary syndromes. Massive
      pulmonary haemorrhage is a rare complication of both clopidogrel and tirofiban.
      Pulmonary haemorrhage may easily be mistaken for acute pulmonary oedema, a
      condition commonly seen in patients with acute coronary syndrome. Physicians need
      to be aware of this diagnostic dilemma because early treatment increases the
      chances of patient survival.

PMID- 14966077
TI  - Haemorrhagic peritonitis as a late complication of echocardiography guided
      pericardiocentesis.
AB  - Clinically significant pericardial effusion is an uncommon complication after
      cardiac surgery. Pericardiocentesis can be performed either through a mini
      sternotomy or under echocardiography guidance. Echocardiography guidance is a
      relatively safe procedure and it avoids the need for another general anaesthetic.
      However, in this post cardiac surgical patient echocardiography guided
      pericardiocentesis was complicated several days later by haemorrhagic
      peritonitis.

PMID- 14966078
TI  - Randomised controlled trial of effect of leaflets to empower patients in
      consultations in primary care.
AB  - OBJECTIVE: To assess the impact of leaflets encouraging patients to raise
      concerns and to discuss symptoms or other health related issues in the
      consultation. DESIGN: Randomised controlled trial. SETTING: Five general
      practices in three settings in the United Kingdom. PARTICIPANTS: 636 consecutive
      patients, aged 16-80 years, randomised to receive a general leaflet, a depression
      leaflet, both, or neither. MAIN OUTCOMES: Mean item score on the medical
      interview satisfaction scale, consultation time, prescribing, referral, and
      investigation. RESULTS: The general leaflet increased patient satisfaction and
      was more effective with shorter consultations (leaflet 0.64, 95% confidence
      interval 0.19 to 1.08; time 0.31, 0.0 to 0.06; interaction between both -0.045, 
      0.08 to-0.009), with similar results for subscales related to the different
      aspects of communication. Thus for a 10 minute consultation the leaflet increased
      satisfaction by 7% (seven centile points) and for a five minute consultation by
      14%. The leaflet overall caused a small non-significant increase in consultation
      time (0.36 minutes, -0.54 to 1.26). Although there was no change in prescribing
      or referral, a general leaflet increased the numbers of investigations (odds
      ratio 1.43, 1.00 to 2.05), which persisted when controlling for the major
      potential confounders of perceived medical need and patient preference (1.87,
      1.10 to 3.19). Most of excess investigations were not thought strongly needed by
      the doctor or the patient. The depression leaflet had no significant effect on
      any outcome. CONCLUSIONS: Encouraging patients to raise issues and to discuss
      symptoms and other health related issues in the consultation improves their
      satisfaction and perceptions of communication, particularly in short
      consultations. Doctors do, however, need to elicit expectations to prevent
      needless investigations.

PMID- 14966079
TI  - Importance of patient pressure and perceived pressure and perceived medical need
      for investigations, referral, and prescribing in primary care: nested
      observational study.
AB  - OBJECTIVE: To assess how pressures from patients on doctors in the consultation
      contribute to referral and investigation. DESIGN: Observational study nested
      within a randomised controlled trial. SETTING: Five general practices in three
      settings in the United Kingdom. PARTICIPANTS: 847 consecutive patients, aged 16
      80 years. MAIN OUTCOMES MEASURES: Patient preferences and doctors' perception of
      patient pressure and medical need. RESULTS: Perceived medical need was the
      strongest independent predictor of all behaviours and confounded all other
      predictors. The doctors thought, however, there was no or only a slight
      indication for medical need among a significant minority of those who were
      examined (89/580, 15%), received a prescription (74/394, 19%), or were referred
      (27/125, 22%) and almost half of those investigated (99/216, 46%). After
      controlling for patient preference, medical need, and clustering by doctor,
      doctors' perceptions of patient pressure were strongly associated with
      prescribing (adjusted odds ratio 2.87, 95% confidence interval 1.16 to 7.08) and
      even more strongly associated with examination (4.38, 1.24 to 15.5), referral
      (10.72, 2.08 to 55.3), and investigation (3.18, 1.31 to 7.70). In all cases,
      doctors' perception of patient pressure was a stronger predictor than patients'
      preferences. Controlling for randomisation group, mean consultation time, or
      patient variables did not alter estimates or inferences. CONCLUSIONS: Doctors'
      behaviour in the consultation is most strongly associated with perceived medical
      need of the patient, which strongly confounds other predictors. However, a
      significant minority of examining, prescribing, and referral, and almost half of
      investigations, are still thought by the doctor to be slightly needed or not
      needed at all, and perceived patient pressure is a strong independent predictor
      of all doctor behaviours. To limit unnecessary resource use and iatrogenesis,
      when management decisions are not thought to be medically needed, doctors need to
      directly ask patients about their expectations.

PMID- 14966080
TI  - PKC activates BKCa channels in rat pulmonary arterial smooth muscle via cGMP
      dependent protein kinase.
AB  - Normally, signaling mechanisms that activate large-conductance, calcium- and
      voltage-activated potassium (BK(Ca)) channels in pulmonary vascular smooth muscle
      cause pulmonary vasodilatation. BK(Ca)-channel modulation is important in the
      regulation of pulmonary arterial pressure, and inhibition (decrease in the
      opening probability) of the BK(Ca) channel has been implicated in the development
      of pulmonary vasoconstriction. Protein kinase C (PKC) causes pulmonary
      vasoconstriction, but little is known about the effect of PKC on BK(Ca)-channel
      activity in pulmonary vascular smooth muscle. Accordingly, studies were done to
      determine the effect of PKC on BK(Ca)-channel activity using patch-clamp studies
      in pulmonary arterial smooth muscle cells (PASMCs) of the Sprague-Dawley rat. The
      PKC activators phorbol myristate acetate (PMA) and thymeleatoxin opened BK(Ca)
      channels in single Sprague-Dawley rat PASMC. The activator response to both PMA
      and thymeleatoxin on BK(Ca)-channel activity was blocked by Go-6983, which
      selectively blocks PKC-alpha, -delta, -gamma, and -zeta, and by rottlerin, which
      selectively inhibits PKC-delta. In addition, the specific cyclic GMP-dependent
      protein kinase antagonist KT-5823 blocked the responses to PMA and thymelatoxin,
      whereas the specific cyclic AMP-dependent protein kinase blocker KT-5720 had no
      effect. In isolated pulmonary arterial vessels, both PMA and forskolin caused
      vasodilatation, which was inhibited by KT-5823, Go-6983, or the BK(Ca)-channel
      blocker tetraethylammonium. The results of this study indicate that activation of
      specific PKC isozymes increases BK(Ca)-channel activity in Sprague-Dawley rat
      PASMC via cyclic GMP-dependent protein kinase, which suggests a unique signaling
      mechanism for vasodilatation.

PMID- 14966081
TI  - Heparin affects signaling pathways stimulated by fibroblast growth factor-1 and 
      2 in type II cells.
AB  - Undersulfation of the basement membrane matrix of alveolar type II (AT2) cells
      compared with that of neighboring type I cells is believed to account for some of
      the known morphological and functional differences between these pneumocytes.
      Heparin, a model for sulfated components of basement membrane matrices, is known
      to inhibit fibroblast growth factor (FGF)-2-stimulated DNA synthesis as well as
      gene expression of FGF-2 and its receptor in AT2 cells. To determine whether
      these end points result from specific effects of heparin on FGF-related signaling
      pathways, isolated rat AT2 cells were treated with 100 ng/ml FGF-1 or FGF-2 in
      the presence of up to 500 microg/ml heparin. In addition, experiments were done
      on cells grown in the presence of 20 mM sodium chlorate (sulfation inhibitor).
      High-dose heparin reduced FGF-1- or FGF-2-stimulated phosphorylation of mitogen
      activated protein kinase kinases (MEK1/2), p44/42 mitogen-activated protein
      kinases (MAPK/ERK1/2), stress-activated protein kinase/c-Jun NH(2)-terminal
      kinase, Akt/protein kinase B, and p90(RSK). FGF-2-stimulated signaling was more
      sensitive to heparin's effects than was signaling stimulated by FGF-1. Heparin
      had an additive effect on the reduced [(3)H]thymidine incorporation in FGF-2
      treated AT2 cells caused by inhibition of the MEK/ERK pathway by the MEK
      inhibitor PD-98059. The data suggest that heparin's known capacity to alter DNA
      synthesis and, possibly, other biological end points is realized via cross talk
      between multiple signaling pathways.

PMID- 14966082
TI  - Roles for early response cytokines during Escherichia coli pneumonia revealed by
      mice with combined deficiencies of all signaling receptors for TNF and IL-1.
AB  - During infection, inflammation is essential for host defense, but it can injure
      tissues and compromise organ function. TNF-alpha and IL-1 (alpha and beta) are
      early response cytokines that facilitate inflammation. To determine the roles of
      these cytokines with overlapping functions, we generated mice deficient in all of
      the three receptors mediating their effects (TNFR1, TNFR2, and IL-1RI). During
      Escherichia coli pneumonia, receptor deficiency decreased neutrophil recruitment
      and edema accumulation to half of the levels observed in wild-type mice. Thus
      these receptors contributed to maximal responses, but substantial inflammation
      progressed independently of them. Receptor deficiency compromised antibacterial
      efficacy for some infectious doses. Decreased ventilation during E. coli
      pneumonia was not affected by receptor deficiency. However, the loss of lung
      compliance during pneumonia was substantially attenuated by receptor deficiency.
      Thus during E. coli pneumonia in mice, the lack of signaling from TNF-alpha and
      IL-1 decreases inflammation and preserves lung compliance.

PMID- 14966083
TI  - Hypofractionation redux?

PMID- 14966084
TI  - Individualized patient dosing in phase I clinical trials: the role of escalation
      with overdose control in PNU-214936.
AB  - PURPOSE: A patient-specific dose-escalation scheme using a Bayesian model of
      Escalation with Overdose Control (EWOC) was conducted to establish the maximum
      tolerated dose (MTD) of PNU-214936 in advanced non-small-cell lung cancer
      (NSCLC). PNU-214936 is a murine Fab fragment of the monoclonal antibody 5T4 fused
      to a mutated superantigen staphylococcal enterotoxin A (SEA). PATIENTS AND
      METHODS: Seventy-eight patients with NSCLC were treated with an individualized
      dose of PNU-214936 calculated using EWOC, based on their anti-SEA antibody level,
      and given as a 3-hour infusion on 4 consecutive days. RESULTS: Fever (82%; grade
      3 to 4, 2.6%) and hypotension (57%; grade 3 to 4, 9%) were the most common
      toxicities. Eight dose-limiting toxicities occurred, as defined as any grade 4
      toxicity occurring within the first 5 days. The MTD was defined as a function of
      pretreatment anti-SEA antibody level. MTD ranged from 103 ng/kg for patients with
      anti-SEA concentrations < or = 10 pmol/mL, to 601 ng/kg for patients with anti
      SEA concentrations of 91 to 150 pmol/mL. A minor tumor response was demonstrated
      in five of 66 assessable patients. CONCLUSION: EWOC determined phase I doses of
      PNU-214936 that were adjusted for patient anti-SEA antibody level, while
      safeguarding against overdose. Furthermore, the method permitted the construction
      of a dosing algorithm that would allow patients in subsequent clinical
      investigations to be treated with a dose of PNU-214936 that is tailored to their
      specific tolerance for the agent, as reflected by their pretreatment anti-SEA.

PMID- 14966085
TI  - NF-kappa B in the vascular progression of melanoma.
AB  - PURPOSE: To examine a model of melanoma progression based on vascular factors and
      the role of NF-kappa B in the vascular progression of melanoma. PATIENTS AND
      METHODS: A data set of 526 patients from the University of California San
      Francisco Melanoma Center with 2 years of follow-up or first relapse was studied.
      The impact of the presence or absence of various prognostic factors on overall
      survival of melanoma patients was assessed using Cox regression and Kaplan-Meier
      analysis. A matched-pair analysis of NF-kappa B expression was performed in cases
      with vascular involvement and increased tumor vascularity versus matched controls
      lacking these factors. RESULTS: Cox regression analysis of factors evaluated by
      the American Joint Committee on Cancer Melanoma Staging Committee reproduced the
      powerful impact of tumor thickness and ulceration in this data set. With the
      inclusion of vascular factors such as tumor vascularity and vascular involvement,
      ulceration was no longer significant in predicting overall survival. By
      multivariate analysis, vascular involvement and tumor vascularity were the
      strongest predictors of melanoma outcome. Tumor vascularity seems to be a
      precursor of both vascular involvement and ulceration. A matched-pair tissue
      array analysis demonstrated the significant correlation between overexpression of
      NF-kappa B-p65 and the development of vascular factors. CONCLUSION: Vascular
      factors play an important role in the progression of malignant melanoma.
      Ulceration may be a surrogate marker for the interactions between melanoma and
      the tumor vasculature. NF-kappa B seems to play an important role in the
      development of these factors.

PMID- 14966086
TI  - Primary cutaneous B-cell lymphoma treated with radiotherapy: a comparison of the
      European Organization for Research and Treatment of Cancer and the WHO
      classification systems.
AB  - PURPOSE: To determine the relationship between the WHO and European Organization
      for Research and Treatment of Cancer (EORTC) pathologic classifications for
      primary cutaneous B-cell lymphoma (CBCL) and the implication of this relationship
      on initial treatment. PATIENTS AND METHODS: Patients with primary CBCL treated
      with radiotherapy were identified retrospectively. Initial biopsy specimens were
      reviewed by two dermatopathologists and classified according to the EORTC and WHO
      systems. Primary outcomes were recurrence-free and overall survival. RESULTS:
      Thirty-four patients were identified; initial biopsy specimens were adequate for
      classification in 32 patients. Four different composite histopathologic subtypes
      of lymphoma were identified: 53% (17 of 32) follicle center cell by EORTC and
      diffuse large B-cell by WHO (FCC/DLB), 25% (eight of 32) follicle center cell by
      EORTC and follicular by WHO (FCC/Fol), 13% (four of 32) marginal zone by EORTC
      and WHO (MZ/MZ), and 9% (three of 32) large B-cell of the leg by EORTC and
      diffuse large B-cell by WHO (Leg/DLB). Five-year relapse-free survival ranged
      from 62% to 73% for FCC/DLB, FCC/Fol, and MZ/MZ but was 33% for Leg/DLB (P =.6).
      Five-year overall survival was 100% for FCC/DLB, FCC/Fol, and MZ/MZ but was 67%
      for Leg/DLB (P =.07). At 5 years, 21% of all patients had developed
      extracutaneous disease. CONCLUSION: Two-thirds of primary cutaneous FCC lymphomas
      by EORTC criteria satisfy WHO criteria for DLB lymphoma. Unlike DLB lymphoma
      presenting in nodal or noncutaneous sites, these lesions are associated with an
      indolent course and may be treated with local radiotherapy alone.

PMID- 14966087
TI  - Impact of body mass index on outcomes and treatment-related toxicity in patients
      with stage II and III rectal cancer: findings from Intergroup Trial 0114.
AB  - PURPOSE: To study the relationship between body mass index (BMI) and rates of
      sphincter-preserving operations, overall survival, cancer recurrence, and
      treatment-related toxicities in patients with rectal cancer. PATIENTS AND
      METHODS: We evaluated a nested cohort of 1,688 patients with stage II and III
      rectal cancer participating in a randomized trial of postoperative fluorouracil
      based chemotherapy and radiation therapy. RESULTS: Obese patients were more
      likely to undergo an abdominoperineal resection (APR) than normal-weight patients
      (odds ratio, 1.77; 95% CI, 1.27 to 2.46). When analyzed by sex, increasing
      adiposity in men was a strong predictor of having an APR (P <.0001). Obese men
      with rectal cancer were also more likely than normal-weight men to have a local
      recurrence (hazard ratio [HR], 1.61; 95% CI, 1.00 to 2.59). In contrast, obesity
      was not predictive of cancer recurrence in women, nor was BMI predictive of
      overall mortality in either men or women. Underweight patients had an increased
      risk of death (HR, 1.43; 95% CI, 1.08 to 1.89) compared with normal-weight
      patients but no increase in cancer recurrences. Among all study participants,
      obese patients had a significantly lower rate of grade 3 to 4 leukopenia,
      neutropenia, and stomatitis and a lower rate of any grade 3 or worse toxicity
      when compared with normal-weight individuals. CONCLUSION: Increasing BMI in male
      patients with rectal cancer is associated with a decreased likelihood of
      sphincter preservation and a higher chance of local recurrence. For both men and
      women, overweight and obese patients experience less toxicity associated with
      adjuvant chemoradiotherapy, suggesting that actual body weight dosing of
      fluorouracil for obese patients is justified.

PMID- 14966088
TI  - Phase II trial of biweekly infusional fluorouracil, folinic acid, and oxaliplatin
      in patients with advanced gastric cancer.
AB  - PURPOSE: To evaluate the toxicity and activity of infusional fluorouracil (FU),
      folinic acid (FA), and oxaliplatin, administered every 2 weeks in patients with
      metastatic gastric cancer. PATIENTS AND METHODS: Forty-one previously untreated
      patients with measurable adenocarcinoma of the stomach were eligible for the
      study. Patients received FU 2.6 g/m(2) (24-hour continuous infusion), FA 500
      mg/m(2) (2-hour intravenous infusion), and oxaliplatin 85 mg/m(2) (2-hour
      intravenous infusion) every 2 weeks for 6 weeks. Treatment was continued until
      progression of disease was observed. RESULTS: All patients were assessable for
      toxicity and 37 of 41 patients were assessable for response. Patient
      characteristics were: sex (male, 28; female,13), median age 60 years (range, 20
      to 77 years), and median Eastern Cooperative Oncology Group performance status of
      1. Response was evaluated every 6 weeks. Of 37 assessable patients, one complete
      and 15 partial remissions were observed (overall response rate, 43%). Stable
      disease was observed in 12 patients (32%) and progressive disease in nine
      patients (24%). The median overall survival was 9.6 months. WHO grade 3 or 4
      hematologic toxicities included neutropenia in two patients (4.9%) and
      thrombocytopenia in one patient (2.4%). Other WHO grade 3 or 4 toxicities
      included diarrhea in three patients (7.3%) and vomiting in two patients (4.9%).
      There were no cases of grade 3 peripheral neuropathy and no treatment-related
      deaths. CONCLUSION: Biweekly fluorouracil, folinic acid, and oxaliplatin is
      active and well-tolerated in patients with advanced gastric cancer. Response
      rates, time to progression, and overall survival were comparable to those
      achieved with other combination chemotherapy regimens, including FOLFOX6, with
      significantly less toxicity.

PMID- 14966089
TI  - EBV-positive gastric adenocarcinomas: a distinct clinicopathologic entity with a
      low frequency of lymph node involvement.
AB  - PURPOSE: Epstein-Barr virus (EBV) is detected in a substantial subgroup of
      gastric adenocarcinomas worldwide. We have previously reported that these EBV
      positive gastric carcinomas carry distinct genomic aberrations. In the present
      study, we analyzed a large cohort of EBV-positive and EBV-negative gastric
      adenocarcinomas for their clinicopathologic features to determine whether they
      constitute a different clinical entity. PATIENTS AND METHODS: Using a validated
      polymerase chain reaction/enzyme immunoassay-based prescreening method in
      combination with EBER1/2-RNA in situ hybridization, EBV was detected in the tumor
      cells of 7.2% (n = 41) of the gastric carcinomas from the Dutch D1D2 trial (N =
      566; mean follow-up, 9 years). EBV status was correlated with clinicopathologic
      features collected for the Dutch D1D2 trial. RESULTS: EBV-positive gastric
      carcinomas occurred significantly more frequently in males (P <.0001) and in
      younger patients (P =.012). Most were of the intestinal type according to the
      Lauren classification (P =.047) or tubular according to the WHO classification (P
      =.006) and located in the proximal part of the stomach (P <.0001). A
      significantly lower tumor-node-metastasis system-stage (P =.026) was observed in
      the patients with EBV-carrying carcinomas, which was solely explained by less
      lymph node (LN) involvement (P =.034) in these cases. In addition, a better
      prognosis, as reflected by a longer disease-free period (P =.04) and a
      significant better cancer-related survival (P =.02), was observed for these
      patients, which could be explained by less LN involvement, less residual disease,
      and younger patient age. CONCLUSION: EBV-carrying gastric adenocarcinomas are a
      distinct entity of carcinomas, characterized not only by unique genomic
      aberrations, but also by distinct clinicopathologic features associated with
      significantly better prognosis.

PMID- 14966090
TI  - An assessment of the utilization of complementary and alternative medication in
      women with gynecologic or breast malignancies.
AB  - PURPOSE: To describe and assess the current utilization of complementary and
      alternative medicines (CAMs) in women with a diagnosis of either gynecologic or
      breast cancer and evaluate their reasons for use. PATIENTS AND METHODS: This
      study included 250 female patients from the Multidisciplinary Breast Center and
      250 patients from the Gynecologic Oncology Center of The University of Texas M.D.
      Anderson Cancer Center (Houston, TX). Patients were selected by having an odd
      numbered medical record number, and they were contacted before their clinic
      visit. The goals of the study were explained, and verbal consent was obtained.
      Patients who agreed to participate were asked to bring a written list and the
      medication bottles of all over-the-counter prescriptions and CAMs with them to
      clinic. In clinic, the investigator obtained a written informed consent and
      administered the survey. All patients and surveys were assessable. RESULTS: The
      most frequently used herbal products and megavitamins/minerals were identified
      from the patient medication histories. Overall, we found the proportion of
      patients using CAM to be 48% (95% CI, 44% to 53%; 241 of 500 patients). CAM use
      was related to patients' educational status: 62% had postgraduate degrees, 50%
      had college degrees, 56% had some college, and 33% had a high school education or
      less. Also, among patients using CAMs, only 53.5% had spoken to a healthcare
      provider regarding CAM therapy. CONCLUSION: The use of CAM is common among women
      with cancer. Studies need to be conducted to establish if there are any potential
      drug interactions and/or therapeutic benefit of CAM products. Moreover, there is
      a need to educate patients and healthcare providers on appropriate and safe use
      of CAM products.

PMID- 14966091
TI  - Human kallikrein 13 protein in ovarian cancer cytosols: a new favorable
      prognostic marker.
AB  - PURPOSE: Human kallikrein 13 (hK13; encoded by the KLK13 gene) is a secreted
      serine protease expressed in endocrine tissues, including the prostate, testis,
      breast, and ovary. We have previously reported steroid hormone regulation of the
      KLK13 gene and its clinical value as a marker of favorable prognosis in breast
      cancer at the mRNA level. We hypothesized that hK13 may represent a potential
      biomarker for ovarian carcinomas. PATIENTS AND METHODS: Using a newly developed
      enzyme-linked immunosorbent assay (ELISA), hK13 levels were quantified in 131
      ovarian tumor extracts and correlated with various clinicopathological variables
      and outcome (progression-free survival [PFS], overall survival [OS]), over a
      median follow-up period of 42 months. RESULTS: hK13 concentration in ovarian
      tumor cytosols ranged from 0 to 18.4 ng/mg of total protein. An optimal cutoff
      value of 0.13 ng/mg (67(th) percentile) was selected, based on the ability of
      hK13 values to predict the PFS of the study population, to categorize tumors as
      hK13-positive or negative. Women with hK13-positive tumors most often had early
      stage (stage I/II) disease, no residual tumor after surgery and optimal debulking
      success (P <.05). Univariate and multivariate Cox regression analyses revealed
      that patients with hK13-positive tumors had a significantly longer PFS and OS
      than hK13-negative patients (P <.05). Kaplan-Meier survival curves further
      confirmed a reduced risk of relapse and death in women with hK13-positive tumors
      (P =.007 and P =.002, respectively). CONCLUSION: These results indicate that hK13
      is an independent marker of favorable prognosis in ovarian cancer.

PMID- 14966092
TI  - Paclitaxel 175 or 225 mg per meters squared with carboplatin in advanced ovarian
      cancer: a randomized trial.
AB  - PURPOSE: To analyze the effect of different doses of paclitaxel with fixed doses
      of carboplatin in the treatment of ovarian cancer. PATIENTS AND METHODS: Patients
      with histologically confirmed epithelial ovarian cancer, International Federation
      of Gynecology and Obstetrics stages IIB to IV, were eligible for this randomized,
      multicenter study. Women were randomly assigned to treatment with (1) carboplatin
      at the dose (in milligrams) corresponding to the following formula: target area
      under the free carboplatin plasma concentration versus time curve (AUC) = 6 x
      (glomerular filtration rate + 25) mg/m(2) (AUC6) plus paclitaxel 175 mg/m(2) for
      six cycles every 21 days or (2) carboplatin AUC6 plus paclitaxel 225 mg/m(2) for
      six cycles every 21 days. A total of 502 women entered the study. RESULTS:
      Pathologic complete response was documented in 132 patients (63.8%) in the 175
      mg/m(2) group and in 127 cases (55.7%) in the 225 mg/m(2) group (chi(2) P =.090).
      The 4-year progression-free survival rate was 41.5% (SE = 3.5) in the 175-mg
      group and 39.2% (SE = 3.5) in the 225-mg group. The corresponding 4-year survival
      rates were 46.2% (based on 115 deaths) and 47.3% (based on 113 deaths),
      respectively. CONCLUSION: This randomized trial suggests that paclitaxel 175
      mg/m(2) plus carboplatin AUC6 is the schedule with a more favorable profile than
      paclitaxel 225 mg/m(2) plus carboplatin AUC6.

PMID- 14966093
TI  - Mammaglobin is associated with low-grade, steroid receptor-positive breast tumors
      from postmenopausal patients, and has independent prognostic value for relapse
      free survival time.
AB  - PURPOSE: The tumor mRNA expression levels of mammaglobin, a novel breast-specific
      and breast cancer-associated marker, were correlated with disease outcome in 280
      patients with primary breast cancer. PATIENTS AND METHODS: Mammaglobin expression
      levels were assessed by quantitative reverse transcriptase polymerase chain
      reaction in frozen tumor tissue from breast cancer patients with a median age of
      60 years (range, 30 to 88 years) and a median follow-up of 85 months (range, 2 to
      169 months). RESULTS: High expression levels were associated with low-grade
      tumors (P =.018), with positive estrogen and progesterone receptor status (P
      <.001), and postmenopausal status (P =.010). In the analysis of all patients, low
      tumor mammaglobin expression levels predicted an early relapse both in Cox
      univariate (hazard ratio [HR], 0.52; 95% CI, 0.34 to 0.79; P =.002) and
      multivariate regression analyses corrected for the traditional prognostic factors
      (HR, 0.55; 95% CI, 0.35 to 0.88; P =.012). The association of mammaglobin
      expression with the rate of relapse was particularly favorable in patients who
      received adjuvant tamoxifen treatment (HR, 0.35; 95% CI, 0.17 to 0.71; P =.004).
      CONCLUSION: These results demonstrate that the assessment of the tumor mRNA
      expression level of the breast-specific protein mammaglobin could be useful to
      stratify patients for individual adjuvant treatment strategies.

PMID- 14966094
TI  - Prognosis of premenopausal breast cancer and childbirth prior to diagnosis.
AB  - PURPOSE: The time interval between last childbirth and subsequent breast cancer
      diagnosis is emerging as an important prognostic factor for premenopausal women.
      PATIENTS AND METHODS: We studied, prospectively, 750 women diagnosed with primary
      invasive breast cancer before age 45 years who participated in the population
      based Australian Breast Cancer Family Study (ABCFS). RESULTS: Median follow-up
      time was 4.9 years (range, 0.8 to 10.8 years). Compared with nulliparous women,
      women who gave birth within 2 years prior to diagnosis were more likely to have
      axillary node-positive (58% v 41%; P =.01), and estrogen receptor-negative (58% v
      39%; P =.005) tumors. The unadjusted hazard ratios for death were 2.3 (95% CI,
      1.3 to 3.8; P =.002), 1.7 (95% CI, 1.1 to 2.6; P =.03), and 0.9 (95% CI, 0.6 to
      1.5; P =.8) for patients who gave birth less than 2 years, 2 to 5 years, and 5 or
      more years before diagnosis, respectively. After adjusting for tumor
      characteristics, these hazard ratios were reduced to 1.9 (95%CI, 1.1 to 3.2; P
      =.02), 1.3 (95% CI, 0.8 to 2.1; P =.3), and 0.9 (95%CI, 0.5 to 1.4; P =.5).
      Modeling showed that, compared with nulliparous women, the mortality hazard ratio
      in parous women was 1.9, decreasing by 8% (95%CI, 4% to 13%; P <.001) for each
      year between last birth and breast cancer diagnosis. CONCLUSION: Proximity of
      last childbirth to subsequent breast cancer diagnosis is a predictor of mortality
      independent of histopathological tumor characteristics. Clinicians should be
      aware that women diagnosed with breast cancer within a few years following
      childbirth may have a worse outcome than that suggested solely by the standard
      histopathological prognostic factors of their cancer.

PMID- 14966095
TI  - Change in neurocognitive functioning after treatment with cranial radiation in
      childhood.
AB  - PURPOSE: To evaluate the pattern of stability and change over time across
      multiple domains of neurocognitive function in radiated survivors of posterior
      fossa (PF) tumors. PATIENTS AND METHODS: Thirty-four children (25 males) treated
      for malignant PF tumors were observed with serial clinical neuropsychologic
      assessments. Thirty patients were treated for medulloblastoma and four patients
      were treated for ependymoma. Twelve patients were treated with reduced-dose and
      21 patients were treated with standard-dose cranial radiation. All patients
      received an additional boost to the PF. One patient was treated with PF radiation
      only. Standardized neuropsychologic tests were administered at different times
      after diagnosis for each child. The rate of change in scores was determined using
      a mixed model regression. RESULTS: Results showed a 2- to 4-point decline per
      year in intelligence scores. For our relatively young sample, intellectual
      function declined quickly in the first few years after treatment, and then more
      gradually. Significant declines in visual-motor integration, visual memory,
      verbal fluency, and executive functioning were also documented. No decline was
      evident for verbal memory and receptive vocabulary. CONCLUSION: Cranial radiation
      is associated with a decline in multiple neurocognitive domains, with a few
      notable exceptions. Our results must be interpreted in the context of common
      limitations of clinical research, including patient variability, changes in test
      versions, small sample size, and clinical referral bias.

PMID- 14966096
TI  - Measuring quality of life in routine oncology practice improves communication and
      patient well-being: a randomized controlled trial.
AB  - PURPOSE: To examine the effects on process of care and patient well-being, of the
      regular collection and use of health-related quality-of-life (HRQL) data in
      oncology practice. PATIENTS AND METHODS: In a prospective study with repeated
      measures involving 28 oncologists, 286 cancer patients were randomly assigned to
      either the intervention group (regular completion of European Organization for
      Research and Treatment of Cancer-Core Quality of Life Questionnaire version 3.0,
      and Hospital Anxiety and Depression Scale on touch-screen computers in clinic and
      feedback of results to physicians); attention-control group (completion of
      questionnaires, but no feedback); or control group (no HRQL measurement in clinic
      before encounters). Primary outcomes were patient HRQL over time, measured by the
      Functional Assessment of Cancer Therapy-General questionnaire, physician-patient
      communication, and clinical management, measured by content analysis of tape
      recorded encounters. Analysis employed mixed-effects modeling and multiple
      regression. RESULTS: Patients in the intervention and attention-control groups
      had better HRQL than the control group (P =.006 and P =.01, respectively), but
      the intervention and attention-control groups were not significantly different (P
      =.80). A positive effect on emotional well-being was associated with feedback of
      data (P =.008), but not with instrument completion (P =.12). A larger proportion
      of intervention patients showed clinically meaningful improvement in HRQL. More
      frequent discussion of chronic nonspecific symptoms (P =.03) was found in the
      intervention group, without prolonging encounters. There was no detectable effect
      on patient management (P =.60). In the intervention patients, HRQL improvement
      was associated with explicit use of HRQL data (P =.016), discussion of pain, and
      role function (P =.046). CONCLUSION: Routine assessment of cancer patients' HRQL
      had an impact on physician-patient communication and resulted in benefits for
      some patients, who had better HRQL and emotional functioning.

PMID- 14966097
TI  - Randomized, double-blind, dose-finding study of dexamethasone in preventing acute
      emesis induced by anthracyclines, carboplatin, or cyclophosphamide:.
AB  - PURPOSE: Different doses and schedules of dexamethasone, combined with a 5-HT3
      antagonist, are used to prevent acute emesis induced by anthracyclines,
      carboplatin, or cyclophosphamide. Therefore, we planned a randomized, double
      blind, dose finding study aimed to identify the preferred dose and schedule of
      dexamethasone. PATIENTS AND METHODS: All consecutive chemotherapy-naive patients
      enrolled onto study were randomly assigned to receive for the prevention of acute
      emesis, during the first 24 hours, one of the following dexamethasone regimens,
      in combination with ondansetron 8 mg intravenously (i.v. ): for arm A, 8 mg i.v.
      before chemotherapy plus 4 mg orally every 6 hours for four doses, starting at
      the same time of the chemotherapy; for arm B, 24 mg i.v. single dose before
      chemotherapy; and for arm C, 8 mg i.v. single dose before chemotherapy. All
      patients received from day 2 to 5 oral dexamethasone 4 mg b.i.d. RESULTS: A total
      of 587 patients were enrolled, and 585 were assessed according to the intention
      to-treat principle (195 patients in each arm). The rate of complete protection
      from acute vomiting and nausea, respectively, was not significantly different
      among the three groups (arm A, 84.6% and 66.7%; arm B, 83.6% and 56.9%; arm C,
      89.2% and 61.0%), nor was the rate of complete protection from delayed vomiting
      and nausea, respectively (arm A, 81.0% and 46.7%; arm B, 81.3% and 45.1%; arm C,
      79.8% and 46.1%). The incidence of delayed vomiting and nausea was strictly
      dependent on the presence of acute vomiting and nausea. Adverse events were mild
      and not significantly different among the three groups. CONCLUSION: Dexamethasone
      8 mg single dose i.v. before chemotherapy, in combination with a 5-HT3
      antagonist, should be considered the preferred dose to prevent acute emesis
      induced by anthracyclines, carboplatin, or cyclophosphamide.

PMID- 14966098
TI  - Enrollment of African Americans onto clinical treatment trials: study design
      barriers.
AB  - PURPOSE: African Americans have the highest cancer mortality rates and poorest
      survival and are more often uninsured and underinsured compared with other ethnic
      groups. Minority participation in clinical trials has traditionally been low,
      with reports ranging from 3% to 20%. The present study systematically assesses
      235 consecutively diagnosed African American cancer patients regarding
      recruitment onto cancer treatment clinical trials at Howard University Cancer
      Center between January 1, 2001, and December 31, 2002. Our intent is to determine
      the rate-limiting factors associated with enrolling African Americans onto
      clinical trials at a historically black medical institution. PATIENTS AND
      METHODS: Two hundred thirty-five consecutively diagnosed African American cancer
      patients were assessed for participation in clinical trials at Howard University
      Hospital and Cancer Center. The study population comprised 165 women and 70 men.
      RESULTS: The overall eligibility rate was 8.5% (20 of 235 patients); however,
      among those eligible, the enrollment rate (ie, enrollment among the eligible
      population) was 60.0% (12 of 20 patients). Comorbidities rendered 17.1% of the
      patient population ineligible for the trials. Advanced disease stage, associated
      with poor performance status, premature death, and short life expectancy, made an
      additional 10% of the patient population ineligible. Respiratory failure, HIV
      positivity, and anemia accounted for 37.8% of the comorbidities in this
      population. Cardiovascular diseases and renal insufficiency represented 16.2% of
      the comorbidities. CONCLUSION: It was evident that study design exclusion and
      inclusion criteria rendered the majority of the study population ineligible.
      Among African Americans, comorbidity is a major issue that warrants considerable
      attention.

PMID- 14966099
TI  - Cancer risks for male carriers of germline mutations in BRCA1 or BRCA2: a review
      of the literature.
AB  - Major risks conferred by BRCA1 and BRCA2 in women are for cancers of the breast,
      ovary, fallopian tube, and peritoneum. Male carriers of mutations in BRCA1 or
      BRCA2 are also susceptible to cancer; however, their risks remain poorly
      understood and their optimal clinical management has not yet been defined. This
      article reviews studies that estimate risk associated with mutations in BRCA1 or
      BRCA2, with a focus on the cancer sites most relevant to men. Male BRCA1 mutation
      carriers are at increased risk of cancers of the prostate and breast. Evidence
      supporting increased susceptibility to colon cancer is limited. In contrast to
      women, who have a greater lifetime risk of cancer with mutations of the BRCA1
      gene, BRCA2 is the more important gene for men. The spectrum of cancers is wide
      for BRCA2 and some studies report that the overall cancer risk for male BRCA2
      carriers exceeds the risk for female carriers. In particular, the relative risk
      to male BRCA2 mutation carriers is high before age 65 years, largely attributable
      to breast, prostate, and pancreatic cancers. BRCA2 mutation carriers are also at
      risk of stomach cancer and melanoma (of the skin and eye). Additional research
      into risks to male BRCA1 or BRCA2 mutation carriers is necessary, specifically to
      determine the magnitude of excess cancer risk among BRCA2 carriers and to
      increase our understanding of the basis for the observed site-specificity in
      cancer development.

PMID- 14966100
TI  - Unusual aspects of melanoma. Case 1. Jejunal malignant melanoma: intestinal or
      unknown primary?

PMID- 14966101
TI  - Unusual aspects of melanoma. Case 2. Regionally advanced nasal cavity melanoma.

PMID- 14966102
TI  - Unusual aspects of melanoma. Case 3. Melanoma-associated retinopathy presenting
      with night blindness.

PMID- 14966103
TI  - Dose-dense chemotherapy as adjuvant treatment for breast cancer.

PMID- 14966104
TI  - Improved outcome with dose-dense chemotherapy.

PMID- 14966105
TI  - Dose density by any other name.

PMID- 14966107
TI  - Trial of antidepressants for mildly depressed cancer patients should have been
      reported in a manner allowing independent evaluation of investigators' claims.

PMID- 14966109
TI  - TGFBR1*6A and cancer: a meta-analysis of 12 case-control studies.

PMID- 14966110
TI  - Transcriptional regulation of the cyclooxygenase-2 gene in macrophages by PU.1.
AB  - Macrophages are an abundant source of cyclooxygenase-2 (COX-2) enzymatic
      products, but a specific mechanism for macrophage COX-2 gene expression has not
      been described. We examined whether PU.1, a myeloid-specific Ets family
      transcription factor, is involved. Sequence analysis revealed two potential c-Ets
      binding sites in the COX-2 promoter (COX-2p) which bind to immunoreactive PU.1.
      Chromatin immunoprecipitation analysis shows inducible PU.1 binding to these
      sites in response to lipopolysaccharide, and COX-2 protein production is
      augmented by ectopic expression of PU.1 but not by PU.1S148A, indicating that
      PU.1 phosphorylation is likely involved. Interestingly, expression of PU.1
      results in acetylation of CCAAT/enhancer-binding protein-beta (C/EBP-beta) and
      increased production of COX-2 protein. Coimmunoprecipitation experiments suggest
      a role for p300 in C/EBP-beta acetylation and COX-2 expression. In contrast, E1A
      inhibits acetylation of C/EBP-beta and is correlated with decreased COX-2
      expression. Together, these data suggest that PU.1 is activated by
      phosphorylation of Ser148 in response to lipopolysaccharide treatment and
      subsequently binds to sequences in the endogenous COX-2p in a time-dependent
      manner. Concomitantly, C/EBP-beta becomes acetylated, and expression of the COX-2
      gene increases. We speculate that a combinatorial role of PU.1 and C/EBP-beta
      mediates the robust production of COX-2 products by macrophages which occurs in
      Gram-negative bacterial sepsis.

PMID- 14966111
TI  - A conserved aspartate (Asp-1393) regulates NADPH reduction of neuronal nitric
      oxide synthase: implications for catalysis.
AB  - Nitric-oxide synthases (NOSs) are flavo-heme enzymes whose electron transfer
      reactions are controlled by calmodulin (CaM). The NOS flavoprotein domain
      includes a ferredoxin-NADP(+) reductase (FNR)-like module that contains NADPH-
      and FAD-binding sites. FNR-like modules in related flavoproteins have three
      conserved residues that regulate electron transfer between bound NAD(P)H and FAD.
      To investigate the function of one of these residues in neuronal NOS (nNOS), we
      generated and characterized mutants that had Val, Glu, or Asn substituted for the
      conserved Asp-1393. All three mutants exhibited normal composition, spectral
      properties, and binding of cofactors, substrates, and CaM. All had slower NADPH
      dependent cytochrome c and ferricyanide reductase activities, which were
      associated with proportionally slower rates of NADPH-dependent flavin reduction
      in the CaM-free and CaM-bound states. Rates of NO synthesis were also
      proportionally slower in the mutants and were associated with slower rates of CaM
      dependent ferric heme reduction. However, a D1393V mutant whose flavins had been
      prereduced with NADPH had a normal rate of heme reduction. This indicated that
      the kinetic defect was restricted to flavin reduction step(s) in the mutants and
      suggested that this limited their catalytic activities. Together, our results
      show the following. 1) The presence and positioning of the Asp-1393 carboxylate
      side chain are critical to enable NADPH-dependent reduction of the nNOS
      flavoprotein. 2) Control of flavin reduction is important because it ensures that
      the rate of heme reduction is sufficiently fast to enable NO synthesis by nNOS.

PMID- 14966112
TI  - Redox studies of subunit interactivity in aerobic ribonucleotide reductase from
      Escherichia coli.
AB  - Ribonucleotide reductase is a heterodimeric (alpha(2)beta(2)) allosteric enzyme
      that catalyzes the conversion of ribonucleotides to deoxyribonucleotides, an
      essential step in DNA biosynthesis and repair. In the enzymatically active form
      aerobic Escherichia coli ribonucleotide reductase is a complex of homodimeric R1
      and R2 proteins. We use electrochemical studies of the dinuclear center to
      clarify the interplay of subunit interaction, the binding of allosteric effectors
      and substrate selectivity. Our studies show for the first time that
      electrochemical reduction of active R2 generates a distinct Met form of the
      diiron cluster, with a midpoint potential (-163 +/- 3 mV) different from that of
      R2(Met) produced by hydroxyurea (-115 +/- 2 mV). The redox potentials of both Met
      forms experience negative shifts when measured in the presence of R1, becoming 
      223 +/- 6 and -226 +/- 3 mV, respectively, demonstrating that R1-triggered
      conformational changes favor one configuration of the diiron cluster. We show
      that the association of a substrate analog and specificity effector (dGDP/dTTP or
      GMP/dTTP) with R1 regulates the redox properties of the diiron centers in R2.
      Their midpoint potential in the complex shifts to -192 +/- 2 mV for dGDP/dTTP and
      to -203 +/- 3 mV for GMP/dTTP. In contrast, reduction potential measurements show
      that the diiron cluster is not affected by ATP (0.35-1.45 mm) and dATP (0.3-0.6
      mm) binding to R1. Binding of these effectors to the R1-R2 complex does not
      perturb the normal docking modes between R1 and R2 as similar redox shifts are
      observed for ATP or dATP associated with the R1-R2 complex.

PMID- 14966113
TI  - p68RacGAP is a novel GTPase-activating protein that interacts with vascular
      endothelial zinc finger-1 and modulates endothelial cell capillary formation.
AB  - The endothelium is required for maintenance of vascular integrity and homeostasis
      during vascular development and in adulthood. However, little is known about the
      coordinated interplay between transcription factors and signaling molecules that
      regulate endothelial cell-dependent transcriptional events. Vascular endothelial
      zinc finger-1 (Vezf1) is a zinc finger-containing transcription factor that is
      specifically expressed within the endothelium during vascular development. We
      have previously shown that Vezf1 potently activates transcription of the
      endothelin-1 promoter. We now report the identification of p68RacGAP, a novel
      Vezf1-interacting 68-kDa RhoGAP domain-containing protein. p68RacGAP mRNA is
      highly expressed in vascular endothelial cells by Northern blot analysis, and
      immunohistochemical staining of adult mouse tissues identified p68RacGAP in
      endothelial cells, vascular smooth muscle cells, and epithelial cells in vivo.
      Rac1 and Vezf1 both bind avidly to p68RacGAP, suggesting that p68RacGAP is not
      only a GTPase-activating protein for Rac1 but that p68RacGAP may also be part of
      the protein complex that binds to and modulates Vezf1 transcriptional activity.
      Functionally p68RacGAP specifically activates the GTPase activity of Rac1 in vivo
      but not Cdc42 or RhoA. In addition, p68RacGAP potently inhibits Vezf1/DB1
      mediated transcriptional activation of the human endothelin-1 promoter and
      modulates endothelial cell capillary tube formation. Taken together, these data
      suggest that p68RacGAP is a multifunctional regulatory protein that has a Rac1
      specific GTPase-activating activity, regulates transcriptional activity of the
      endothelin-1 promoter, and is involved in the signal transduction pathway that
      regulates endothelial cell capillary tube formation during angiogenesis.

PMID- 14966114
TI  - Mechanism of genetic complementation of ammonium transport in yeast by human
      erythrocyte Rh-associated glycoprotein.
AB  - The Rh blood group proteins are erythrocyte proteins important in neonatal and
      transfusion medicine. Recent studies have shed new light on the possible
      biological function of Rh proteins as members of a conserved family of proteins
      involved in ammonium transport. The erythrocyte Rh-associated glycoprotein (RhAG)
      mediates uptake of ammonium when expressed in Xenopus laevis oocytes, and
      functional studies indicate that RhAG might function as an NH(4)(+)-H(+)
      exchanger. To further delineate the functional properties of RhAG, in this study
      we have expressed RhAG in both a Saccharomyces cerevisiae ammonium-transport
      mutant (mep1Delta mep2Delta mep3Delta) and a wild-type strain. RhAG was able to
      complement the transport mutant, with complementation strictly pH-dependent,
      requiring pH 6.2-6.5. RhAG also conferred resistance to methylamine (MA), a toxic
      analog of ammonium, and expression in wild-type cells revealed that resistance
      was correlated with efflux of MA. RhAG-mediated resistance was pH-dependent,
      being optimal at acid pH. The opposite pH dependence of ammonium complementation
      (uptake) and MA resistance (efflux) is consistent with bidirectional movement of
      substrate counter to the direction of the proton gradient. This report clarifies
      and expands previous observations of RhAG-mediated transport in yeast and
      supports the hypothesis that ammonium transport is coupled to the H(+) gradient
      and that RhAG functions as a NH(4)(+)/H(+) exchanger.

PMID- 14966115
TI  - The -4 phenylalanine is required for substrate ubiquitination catalyzed by HECT
      ubiquitin ligases.
AB  - The reaction cycle of HECT domain ubiquitin ligases consists of three steps: 1)
      binding of an E2 protein, 2) transfer of ubiquitin from E2 to the HECT domain,
      and 3) transfer of ubiquitin to the substrate. We report the identification of a
      determinant that is specifically required for the last step of this cycle, a
      phenylalanine residue located four amino acids from the C terminus of most HECT
      domains, referred to here as the -4F. Alteration of this residue in human E6AP
      and Saccharomyces cerevisae Rsp5p did not affect ubiquitin-thioester formation,
      but effectively blocked substrate ubiquitination. Alteration of the -4F to
      alanine with concomitant substitution of a nearby residue to phenylalanine only
      partially restored Rsp5p activity, indicating that precise spatial placement of
      this residue is important. C-terminally extended E6AP and Rsp5p proteins were
      also defective for substrate ubiquitination, providing a likely biochemical
      understanding of a previously isolated Angelman syndrome-associated mutation of
      E6AP that alters the stop codon of an otherwise wild-type gene. We propose that
      the -4F may play a role in orienting ubiquitin when it is tethered to the HECT
      active site cysteine. This may be necessary to allow for approach of the incoming
      lysine epsilon-amino group of the substrate.

PMID- 14966116
TI  - Plectin-RACK1 (receptor for activated C kinase 1) scaffolding: a novel mechanism
      to regulate protein kinase C activity.
AB  - Agonist-induced translocation of protein kinase C (PKC) isozymes is mediated by
      receptors for the activated form of the kinase, shuttling it from one
      intracellular site to another and enhancing its catalytic activity. It is however
      unknown whether the receptors themselves are anchored to certain intracellular
      structures prior to their engagement with PKC. We show here sequestering of
      receptor for activated C kinase 1 (RACK1) to the cytoskeleton through the
      cytoskeletal linker protein plectin during the initial stages of cell adhesion.
      We found that upon PKC activation, RACK1 was released from the cytoskeleton and
      transferred to the detergent-soluble cell compartment, where it formed an
      inducible triple complex with one of the PKC isozymes, PKCdelta, and with
      plectin. In plectin-deficient cells the cytoskeleton-associated RACK1 fraction
      was reduced, and the protein was found predominantly at sites to which it
      normally translocated upon PKC activation. Concomitantly, dislocation of PKCdelta
      and elevated enzymatic activity were observed in these cells. PKCdelta was also
      more rapidly degraded, likely due to its overactivation. We propose a previously
      unrecognized function of plectin as cytoskeletal regulator of PKC signaling, and
      possibly other signaling events, through sequestration of the scaffolding protein
      RACK1.

PMID- 14966117
TI  - Arsenic trioxide uptake by hexose permeases in Saccharomyces cerevisiae.
AB  - Arsenic trioxide is a toxic metalloid and carcinogen that is also used as an
      anticancer drug, and for this reason it is important to identify the routes of
      arsenite uptake by cells. In this study the ability of hexose transporters to
      facilitate arsenic trioxide uptake in Saccharomyces cerevisiae was examined. In
      the absence of glucose, strains with disruption of the arsenite efflux gene ACR3
      accumulated high levels of (73)As(OH)(3). The addition of glucose inhibited
      uptake by approximately 80%. Disruption of FPS1, the aquaglyceroporin gene,
      reduced glucose-independent uptake by only about 25%, and the residual uptake was
      nearly completely inhibited by hexoses, including glucose, galactose, mannose,
      and fructose but not pentoses or disaccharides. A strain lacking FPS1, ACR3, and
      all genes for hexose permeases except for HXT3, HXT6, HXT7, and GAL2 exhibited
      hexose-inhibitable (73)As(OH)(3) uptake, whereas a strain lacking all 18 hexose
      transport-related genes (HXT1 to HXT17 and GAL2), FPS1 and ACR3, exhibited <10%
      of wild type (73)As(OH)(3) transport. When HXT1, HXT3, HXT4, HXT5, HXT7, or HXT9
      was individually expressed in that strain, hexose-inhibitable (73)As(OH)(3)
      uptake was restored. In addition, the transport of [(14)C]glucose was inhibited
      by As(OH)(3). These results clearly demonstrate that hexose permeases catalyze
      the majority of the transport of the trivalent metalloid arsenic trioxide.

PMID- 14966118
TI  - Deletion of dentin matrix protein-1 leads to a partial failure of maturation of
      predentin into dentin, hypomineralization, and expanded cavities of pulp and root
      canal during postnatal tooth development.
AB  - The dentin matrix protein-1 (DMP-1) gene is identified in odontoblasts during
      both embryonic and postnatal development. In vitro study suggests that this
      noncollagen acidic phosphoprotein plays a role in mineralization. However,
      deletion of the Dmp-1 gene has little effect on tooth development during
      embryogenesis. To address the role of DMP-1 in tooth during postnatal
      development, we analyzed changes of dentinogenesis in Dmp-1 null mice from 3 days
      after birth to 1 year. Here we show that Dmp-1 null mice postnatally develop a
      profound tooth phenotype characterized by a partial failure of maturation of
      predentin into dentin, enlarged pulp chambers, increased width of predentin zone
      with reduced dentin wall, and hypomineralization. The tooth phenotype of these
      mice is strikingly similar to that in dentin sialophosphoprotein (Dspp) null mice
      and shares some features of the human disease dentinogenesis imperfecta III. We
      have also demonstrated that DSPP levels are reduced in Dmp-1 null mice,
      suggesting that DSPP is probably regulated by DMP-1 during dentinogenesis.
      Finally, we show the absence or delayed development of the third molar in Dmp-1
      null mice, which is probably secondary to defects in Dmp-1 null bone. Taken
      together, these studies suggest that DMP-1 is essential for later dentinogenesis
      during postnatal development.

PMID- 14966119
TI  - Crystal structure of the dioxygen-bound heme oxygenase from Corynebacterium
      diphtheriae: implications for heme oxygenase function.
AB  - HmuO, a heme oxygenase of Corynebacterium diphtheriae, catalyzes degradation of
      heme using the same mechanism as the mammalian enzyme. The oxy form of HmuO, the
      precursor of the catalytically active ferric hydroperoxo species, has been
      characterized by ligand binding kinetics, resonance Raman spectroscopy, and x-ray
      crystallography. The oxygen association and dissociation rate constants are 5
      microm(-1) s(-1) and 0.22 s(-1), respectively, yielding an O(2) affinity of 21
      microm(-1), which is approximately 20 times greater than that of mammalian
      myoglobins. However, the affinity of HmuO for CO is only 3-4-fold greater than
      that for mammalian myoglobins, implying the presence of strong hydrogen bonding
      interactions in the distal pocket of HmuO that preferentially favor O(2) binding.
      Resonance Raman spectra show that the Fe-O(2) vibrations are tightly coupled to
      porphyrin vibrations, indicating the highly bent Fe-O-O geometry that is
      characteristic of the oxy forms of heme oxygenases. In the crystal structure of
      the oxy form the Fe-O-O angle is 110 degrees, the O-O bond is pointed toward the
      heme alpha-meso-carbon by direct steric interactions with Gly-135 and Gly-139,
      and hydrogen bonds occur between the bound O(2) and the amide nitrogen of Gly-139
      and a distal pocket water molecule, which is a part of an extended hydrogen
      bonding network that provides the solvent protons required for oxygen activation.
      In addition, the O-O bond is orthogonal to the plane of the proximal imidazole
      side chain, which facilitates hydroxylation of the porphyrin alpha-meso-carbon by
      preventing premature O-O bond cleavage.

PMID- 14966120
TI  - Factors binding a non-classical Cis-element prevent heterochromatin effects on
      locus control region activity.
AB  - A locus control region (LCR) is a cis-acting gene-regulatory element capable of
      transferring the expression characteristics of its gene locus of origin to a
      linked transgene. Furthermore, it can do this independently of the site of
      integration in the genome of transgenic mice. Although most LCRs contain
      subelements with classical transcriptional enhancer function, key aspects of LCR
      activity are supported by cis-acting sequences devoid of the ability to act as
      direct transcriptional enhancers. Very few of these "non-enhancer" LCR components
      have been characterized. Consequently, the sequence requirements and molecular
      bases for their functions, as well as their roles in LCR activity, are poorly
      understood. We have investigated these questions using the LCR from the mouse T
      cell receptor (TCR) alpha/Dad1 gene locus. Here we focus on DNase hypersensitive
      site (HS) 6 of the TCRalpha LCR. HS6 does not support classical enhancer
      activity, yet has gene regulatory activity in an in vivo chromatin context. We
      have identified three in vivo occupied factor-binding sites within HS6, two of
      which interact with Runx1 and Elf-1 factors. Deletion of these sites from the LCR
      impairs its activity in vivo. This mutation renders the transgene locus
      abnormally inaccessible in chromatin, preventing the normal function of other LCR
      subelements and reducing transgene mRNA levels. These data show these factor
      binding sites are required for preventing heterochromatin formation and indicate
      that they function to maintain an active TCRalpha LCR assembly in vivo.

PMID- 14966121
TI  - Mechanistic relationship between androgen receptor polyglutamine tract truncation
      and androgen-dependent transcriptional hyperactivity in prostate cancer cells.
AB  - Androgen receptor (AR) signaling pathways mediate critical events in normal and
      neoplastic prostate growth. Shortening of the polymorphic N-terminal
      polyglutamine (poly(Q)) tract of the AR gene leads to transcriptional
      hyperactivity and has been correlated with an increased risk of prostate cancer.
      The underlying mechanisms for these effects are poorly understood. We show here
      that androgen-dependent cellular proliferation and transcription in prostate
      cancer cells is inversely correlated to the length of the AR poly(Q) region. We
      further show that AR proteins containing a shortened poly(Q) region functionally
      respond to lower concentrations of androgens than wild type AR. Whereas DNA
      binding activity is relatively unaffected by AR poly(Q) variation, we found that
      ligand binding affinity and the ligand-induced NH(2)- to COOH-terminal
      intramolecular interaction is enhanced when the poly(Q) region is shortened.
      Importantly, we show that AR proteins containing a shortened poly(Q) region
      associate in vivo with higher levels of specific p160 coactivators and components
      of the SWI/SNF chromatin remodeling complex as compared with the wild type AR.
      Collectively, our findings suggest that the AR transcriptional hyperactivity
      associated with shortened poly(Q) length stems from altered ligand-induced
      conformational changes that enhance coactivator recruitment.

PMID- 14966122
TI  - The catalytic and kinetic mechanisms of NADPH-dependent alkenal/one
      oxidoreductase.
AB  - NADPH-dependent alkenal/one oxidoreductase (AOR) from the rat is a phase
      2/antioxidative enzyme that is known to catalyze the reduction of the carbon
      carbon double bond of alpha,beta-unsaturated aldehydes and ketones. It is also
      known for its leukotriene B(4) 12-hydroxydehydrogenase activity. In order to
      begin to understand these dual catalytic activities and validate its
      classification as a reductase of the medium-chain dehydrogenase/reductase family,
      an investigation of the mechanism of its NADPH-dependent activity was undertaken.
      Recombinant AOR and a 3-nonen-2-one substrate were used to perform steady-state
      initial velocity, product inhibition, and dead end inhibition experiments, which
      elucidated an ordered Theorell-Chance kinetic mechanism with NADPH binding first
      and NADP(+) leaving last. A nearly 20-fold preference for NADPH over NADH was
      also observed. The dependence of kinetic parameters V and V/K on pH suggests the
      involvement of a general acid with a pK of 9.2. NADPH isomers stereospecifically
      labeled with deuterium at the 4-position were used to determine that AOR
      catalyzes the transfer of the pro-R hydride to the beta-carbon of an alpha,beta
      unsaturated ketone, illudin M. Two-dimensional nuclear Overhauser effect NMR
      spectra demonstrate that this atom becomes the R-hydrogen at this position on the
      metabolite. Using [4R-(2)H]NADPH, small primary kinetic isotope effects of 1.16
      and 1.73 for V and V/K, respectively, were observed and suggest that hydride
      transfer is not rate-limiting. Atomic absorption spectroscopy indicated an
      absence of Zn(2+) from active preparations of AOR. Thus, AOR fits predictions
      made for medium-chain reductases and bears similar characteristics to well known
      medium-chain alcohol dehydrogenases.

PMID- 14966123
TI  - Critical upstream signals of cytochrome C release induced by a novel Bcl-2
      inhibitor.
AB  - Cytochrome c release is a central step in the apoptosis induced by many death
      stimuli. Bcl-2 plays a critical role in controlling this step. In this study, we
      investigated the upstream mechanism of cytochrome c release induced by ethyl 2
      amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA14-1),
      a recently discovered small molecule inhibitor of Bcl-2. HA14-1 was found to
      induce cytochrome c release from the mitochondria of intact cells but not from
      isolated mitochondria. Cytochrome c release from isolated mitochondria requires
      the presence of both HA14-1 and exogenous Ca(2+). This suggests that both
      mitochondrial and extramitochondrial signals are important. In intact cells,
      treatment with HA14-1 caused Ca(2+) spike, change in mitochondrial membrane
      potential (Delta psi(m)) transition, Bax translocation, and reactive oxygen
      species (ROS) generation prior to cytochrome c release. Pretreatment with either
      EGTA acetoxymethyl ester or vitamin E resulted in a significant decrease in
      cytochrome c release and cell death induced by HA14-1. Furthermore pretreatment
      with RU-360, an inhibitor of the mitochondrial Ca(2+) uniporter, or with EGTA
      acetoxymethyl ester, but not with vitamin E, prevented the HA14-1-induced Delta
      psi(m) transition and Bax translocation. This suggests that ROS generation is an
      event that occurs after the Delta psi(m) transition and Bax translocation.
      Together these data demonstrate that the Ca(2+) spike, mitochondrial Bcl-2
      presensitization, and subsequent Delta psi(m) transition, Bax translocation, and
      ROS generation are important upstream signals for cytochrome c release upon HA14
      1 stimulation. The involvement of endoplasmic reticulum and mitochondrial signals
      suggests both organelles are crucial for HA14-1-induced apoptosis.

PMID- 14966124
TI  - Characterization of the metabolic flux and apoptotic effects of O-hydroxyl- and N
      acyl-modified N-acetylmannosamine analogs in Jurkat cells.
AB  - The supplementation of the sialic acid biosynthetic pathway with exogenously
      supplied N-acetylmannosamine (ManNAc) analogs has many potential biomedical and
      biotechnological applications. In this work, we explore the structure-activity
      relationship of Man-NAc analogs on cell viability and metabolic flux into the
      sialic acid biosynthetic pathway to gain a better understanding of the
      fundamental biology underlying "glycosylation engineering" technology. A panel of
      ManNAc analogs bearing various modifications on the hydroxyl groups as well as
      substitutions at the N-acyl position was investigated. Increasing the carbon
      chain length of ester derivatives attached to the hydroxyl groups increased the
      metabolic efficiency of sialic acid production, whereas similar modification to
      the N-acyl group decreased efficiency. In both cases, increases in chain length
      decreased cell viability; DNA ladder formation, Annexin V-FITC two-dimensional
      flow cytometry assays, caspase-3 activation, and down-regulation of
      sialoglycoconjugate-processing enzymes established that the observed growth
      inhibition and toxicity resulted from apoptosis. Two of the panel of 12 analogs
      tested, specifically Ac(4)ManNLev and Ac(4) ManNHomoLev, were highly toxic.
      Interestingly, both of these analogs maintained a ketone functionality in the
      same position relative to the core monosaccharide structure, and both also
      inhibited flux through the sialic acid pathway (the remainder of the less toxic
      analogs either increased or had no measurable impact on flux). These results
      provide fundamental insights into the role of sialic acid metabolism in apoptosis
      by demonstrating that ManNAc analogs can modulate apoptosis both indirectly via
      hydroxylgroup effects and directly through N-acyl-group effects.

PMID- 14966125
TI  - Proximal and distal sequences control UV cone pigment gene expression in
      transgenic zebrafish.
AB  - The molecular basis of cone photoreceptor-specific gene expression is largely
      unknown. In this study, we define cis-acting DNA sequences that control the cell
      type-specific expression of the zebrafish UV cone pigment gene by transient
      expression of green fluorescent protein transgenes following their injection into
      zebrafish embryos. These experiments show that 4.8 kb of 5'-flanking sequences
      from the zebrafish UV pigment gene direct expression specifically to UV cones and
      that this activity requires both distal and proximal sequences. In addition, we
      demonstrate that a proximal region located between -215 and -110 bp (with respect
      to the initiator methionine codon) can function in the context of a zebrafish
      rhodopsin promotor to convert its specificity from rod-only expression to rod and
      UV cone expression. These experiments demonstrate the power of transient
      transgenesis in zebrafish to efficiently define cis-acting regulatory sequences
      in an intact vertebrate.

PMID- 14966126
TI  - Kinetic characterization of bifunctional thymidylate synthase-dihydrofolate
      reductase (TS-DHFR) from Cryptosporidium hominis: a paradigm shift for ts
      activity and channeling behavior.
AB  - This study presents a kinetic characterization of the recently crystallized
      bifunctional thymidylate synthasedihydrofolate reductase (TS-DHFR) enzyme from
      the apicomplexa parasite, Cryptosporidium hominis. Our study focuses on
      determination of the C. hominis TS-DHFR kinetic mechanism, substrate channeling
      behavior, and domain-domain communication. Unexpectedly, the unique mechanistic
      features of C. hominis TS-DHFR involve the highly conserved TS domain. At 45 s(-)
      (1), C. hominis TS activity is 10-40-fold faster than other TS enzymes studied
      and a new kinetic mechanism was required to simulate C. hominis TS behavior. A
      large accumulation of dihydrofolate produced at TS and a lag in product formation
      at DHFR were observed. These observations make C. hominis TS-DHFR the first
      bifunctional TS-DHFR enzyme studied for which there is clear evidence against
      dihydrofolate substrate channeling. Furthermore, whereas with Leishmania major TS
      DHFR there are multiple lines of evidence for domain-domain communication (ligand
      binding at one active site affecting activity of the other enzyme), no such
      effects were observed with C. hominis TS-DHFR.

PMID- 14966127
TI  - In vivo hyaluronan synthesis upon expression of the mammalian hyaluronan synthase
      gene in Drosophila.
AB  - Hyaluronan (HA) is a large linear polymer of repeating disaccharides of
      glucuronic acid and GlcNAc. Although HA is widely distributed in vertebrate
      animals, it has not been found in invertebrates, including insect species.
      Insects utilize chitin, a repeating beta-1,4-linked homopolymer of GlcNAc, as a
      major component of their exoskeleton. Recent studies illustrate the similarities
      in the biosynthetic mechanisms of HA and chitin and suggest that HA synthase
      (HAS) and chitin synthase have evolved from a common ancestral molecule. Although
      the biochemical properties and in vivo functions of HAS proteins have been
      extensively studied, the molecular basis for HA biosynthesis is not completely
      understood. For example, it is currently not clear if proper chain elongation and
      secretion of HA require other components in addition to HAS. Here, we demonstrate
      that a non-HA-synthesizing animal, the fruit fly Drosophila melanogaster, can
      produce HA in vivo when a single HAS protein is introduced. Expression of the
      mouse HAS2 gene in Drosophila tissues by the Gal4/UAS (upstream activating
      sequence) system resulted in massive HA accumulation in the extracellular space
      and caused various morphological defects. These morphological abnormalities were
      ascribed to disordered cell-cell communications due to accumulation of HA rather
      than disruption of heparan sulfate synthesis. We also show that adult wings with
      HA can hold a high level of water. These findings demonstrate that organisms
      synthesizing chitin (but not HA) are capable of producing HA that is structurally
      and functionally relevant to that in mammals. The ability of insect cells to
      produce HA supports the idea that in vivo HA biosynthesis does not require
      molecules other than the HAS protein. An alternative model is that Drosophila
      cells use endogenous components of the chitin biosynthetic machinery to produce
      and secrete HA.

PMID- 14966128
TI  - Structural requirements for signal transducer and activator of transcription 3
      binding to phosphotyrosine ligands containing the YXXQ motif.
AB  - Stat3 is an Src homology (SH)2-containing protein constitutively activated in a
      wide variety of human cancers following its recruitment to YXXQ-containing
      motifs, which results in resistance to apoptosis. Despite resolution of the
      crystal structure of Stat3 homodimer bound to DNA, the structural basis for the
      unique specificity of Stat3 SH2 for YXXQ-containing phosphopeptides remains
      unresolved. We tested three models of this interaction based on computational
      analysis of available structures and sequence alignments, two of which assumed an
      extended peptide configuration and one in which the peptide had a beta-turn. By
      using peptide immunoblot affinity assays and mirror resonance affinity analysis,
      we demonstrated that only phosphotyrosine (Tyr(P)) peptides containing +3 Gln
      (not Leu, Met, Glu, or Arg) bound to wild type Stat3. Examination of a series of
      wild type and mutant Stat3 proteins demonstrated loss of binding to pYXXQ
      containing peptides only in Stat3 mutated at Lys-591 or Arg-609, whose side
      chains interact with the Tyr(P) residue, and Stat3 mutated at Glu-638, whose
      amide hydrogen bonds with oxygen within the +3 Gln side chain when the peptide
      ligand assumes a beta-turn. These findings support a model for Stat3 SH2
      interactions that could form the basis for anticancer drugs that specifically
      target Stat3.

PMID- 14966129
TI  - Crystal structures of human bifunctional enzyme aminoimidazole-4-carboxamide
      ribonucleotide transformylase/IMP cyclohydrolase in complex with potent sulfonyl
      containing antifolates.
AB  - Aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/IMP
      cyclohydrolase (ATIC) is a bifunctional enzyme with folate-dependent AICAR
      transformylase and IMP cyclohydrolase activities that catalyzes the last two
      steps of purine biosynthesis. The AICAR transformylase inhibitors BW1540 and
      BW2315 are sulfamido-bridged 5,8-dideazafolate analogs with remarkably potent
      K(i) values of 8 and 6 nm, respectively, compared with most other antifolates.
      Crystal structures of ATIC at 2.55 and 2.60 A with each inhibitor, in the
      presence of substrate AICAR, revealed that the sulfonyl groups dominate inhibitor
      binding and orientation through interaction with the proposed oxyanion hole.
      These agents then appear to mimic the anionic transition state and now implicate
      Asn(431') in the reaction mechanism along with previously identified key
      catalytic residues Lys(266) and His(267). Potent and selective inhibition of the
      AICAR transformylase active site, compared with other folate-dependent enzymes,
      should therefore be pursued by further design of sulfonyl-containing antifolates.

PMID- 14966130
TI  - Hetero-oligomerization between GABAA and GABAB receptors regulates GABAB receptor
      trafficking.
AB  - The neurotransmitter gamma-aminobutyric acid (GABA) mediates inhibitory signaling
      in the brain via stimulation of both GABA(A) receptors (GABA(A)R), which are
      chloride-permeant ion channels, and GABA(B) receptors (GABA(B)R), which signal
      through coupling to G proteins. Here we report physical interactions between
      these two different classes of GABA receptor. Association of the GABA(B) receptor
      1 (GABA(B)R1) with the GABA(A) receptor gamma2S subunit robustly promotes cell
      surface expression of GABA(B)R1 in the absence of GABA(B)R2, a closely related
      GABA(B) receptor that is usually required for efficient trafficking of GABA(B)R1
      to the cell surface. The GABA(B)R1/gamma2S complex is not detectably functional
      when expressed alone, as assessed in both ERK activation assays and physiological
      analyses in oocytes. However, the gamma2S subunit associates not only with
      GABA(B)R1 alone but also with the functional GABA(B)R1/GABA(B)R2 heterodimer to
      markedly enhance GABA(B) receptor internalization in response to agonist
      stimulation. These findings reveal that the GABA(B)R1/gamma2S interaction results
      in the regulation of multiple aspects of GABA(B) receptor trafficking, allowing
      for cross-talk between these two distinct classes of GABA receptor.

PMID- 14966131
TI  - An intronic polypyrimidine-rich element downstream of the donor site modulates
      cystic fibrosis transmembrane conductance regulator exon 9 alternative splicing.
AB  - Two intronic elements, a polymorphic TGmTn locus at the end of intron 8 and an
      intronic splicing silencer in intron 9, regulate aberrant splicing of human
      cystic fibrosis transmembrane conductance regulator (CFTR) exon 9. Previous
      studies (Pagani, F., Buratti, E., Stuani, C., Romano, M., Zuccato, E., Niksic,
      M., Giglio, L., Faraguna, D., and Baralle, F. E. (2000) J. Biol. Chem. 275, 21041
      21047 and Buratti, E., Dork, T., Zuccato, E., Pagani, F., Romano, M., and
      Baralle, F. E. (2001) Embo J. 20, 1774-1784) have demonstrated that trans-acting
      factors that bind to these sequences, TDP43 and Ser/Arg-rich proteins,
      respectively, mediate splicing inhibition. Here, we report the identification of
      two polypyrimidine-binding proteins, TIA-1 and polypyrimidine tract-binding
      protein (PTB), as novel players in the regulation of CFTR exon 9 splicing. In
      hybrid minigene experiments, TIA-1 induced exon inclusion, whereas PTB induced
      exon skipping. TIA-1 bound specifically to a polypyrimidine-rich controlling
      element (PCE) located between the weak 5'-splice site (ss) and the intronic
      splicing silencer. Mutants of the PCE polypyrimidine motifs did not bind TIA-1
      and, in a splicing assay, did not respond to TIA-1 splicing enhancement. PTB
      antagonized in vitro TIA-1 binding to the PCE, but its splicing inhibition was
      independent of its binding to the PCE. Recruitment of U1 small nuclear RNA to the
      weak 5'-ss by complementarity also induced exon 9 inclusion, consistent with the
      facilitating role of TIA-1 in weak 5'-ss recognition by U1 small nuclear
      ribonucleoprotein. Interestingly, in the presence of a high number of TG repeats
      and a low number of T repeats in the TGmTn locus, TIA-1 activated a cryptic
      exonic 3'-ss. This effect was independent of both TIA-1 binding to the PCE and U1
      small nuclear RNA recruitment to the 5'-ss. Moreover, it was abolished by
      deletion of either the TG or T sequence. These data indicate that, in CFTR exon
      9, TIA-1 binding to the PCE recruits U1 small nuclear ribonucleoprotein to the
      weak 5'-ss and induces exon inclusion. The TIA-1-mediated alternative usage of
      the 3'-splice sites, which depends on the composition of the unusual TGmTn
      element, represents a new mechanism of splicing regulation by TIA-1.

PMID- 14966132
TI  - A predominant role of acyl-CoA:monoacylglycerol acyltransferase-2 in dietary fat
      absorption implicated by tissue distribution, subcellular localization, and up
      regulation by high fat diet.
AB  - Acyl-CoA:monoacylglycerol acyltransferase-2 (MGAT2) catalyzes the synthesis of
      diacylglycerol and differs from the MGAT1 and MGAT3 in tissue distribution at the
      mRNA level. In addition to the small intestine, MGAT2 mRNA is also expressed at
      high levels in human liver, the lower gastrointestinal tract, and the mouse
      kidney, but the physiological significance of such expression has not yet been
      studied. Using an affinity-purified antibody, the present study investigated the
      expression of murine MGAT2 protein along the intestinal tract, determined its
      subcellular localization, and studied its regulation by diet and in db/db mouse.
      Results demonstrate a high level of MGAT2 expression in the small intestine in a
      proximal-to-distal gradient that correlated well with both MGAT enzyme activity
      and fat absorption pattern. In contrast, MGAT2 protein was not detectable in
      other sections of the digestive tract, including stomach, cecum, colon, and
      rectum, or other mouse tissues such as kidney, liver, and adipocytes.
      Immunohistological studies provided direct evidence that the enzyme is expressed
      not only in the villi, but also in the crypt regions of the small intestine,
      which suggests that MGAT2 expression occurs prior to the maturation of
      enterocytes. MGAT2 is localized in the endoplasmic reticulum (ER) in both MGAT2
      transfected COS-7 and Caco-2 cells, indicating that the ER is the primary site
      for dietary fat re-synthesis. MGAT2 expression appeared not to be affected by
      diabetes in the db/db mouse, however, the total intestinal MGAT activity was
      significantly enhanced. Finally, an up-regulation of both MGAT2 protein
      expression and MGAT activity was observed in mice fed a high fat diet,
      implicating a role of MGAT2 in diet-induced obesity. Taken together, our data
      suggest a predominant role of MGAT2 in dietary fat absorption.

PMID- 14966133
TI  - Cofactor hydrogen bonding onto the protein main chain is conserved in the short
      chain dehydrogenase/reductase family and contributes to nicotinamide orientation.
AB  - Human estrogenic 17beta-hydroxysteroid dehydrogenase (17beta-HSD1), a member of
      the short chain dehydrogenase/reductase (SDR) family, is responsible for the
      biosynthesis of all active estrogens. The crystal structures of two C19-steroid
      ternary complexes (17beta-HSD1-androstanedione-NADP and 17beta-HSD1
      androstenedione-NADP) reveal the critical role of Leu149 in regulating the
      substrate specificity and provide novel insight into the different fates of a
      conserved glutamate residue in the estrogen-specific proteins upon the binding of
      the keto and hydroxyl groups of steroids. The whole NADP molecule can be
      unambiguously defined in the NADP binary complex, whereas both ternary complexes
      show that the nicotinamide moiety of NADP cannot be located in the density maps.
      In both ternary complexes, the expected position of carboxamide oxygen of NADP is
      occupied by a water molecule, which makes a bifurcated hydrogen bond with the O3
      of C19-steroid and the main chain nitrogen of Val188. These results demonstrate
      that the hydrogen bonding interaction between the main chain amide group and the
      carboxamide group of NAD(P)(H) plays an important role in anchoring the
      nicotinamide ring to the enzyme. This finding is substantiated by structural
      analyses of all 33 NAD(P)(H) complexes of different SDR proteins, because 29
      structures of 33 show this interaction. This common feature reveals a general
      mechanism among the SDR family, providing a rational basis for inhibitor design
      against biologically relevant SDR targets.

PMID- 14966134
TI  - Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like
      receptor 2 dimerized with Toll-like receptor 6 or 1.
AB  - Toll-like receptor 4 (TLR4) and TLR2 agonists from bacterial origin require
      acylated saturated fatty acids in their molecules. Previously, we reported that
      TLR4 activation is reciprocally modulated by saturated and polyunsaturated fatty
      acids in macrophages. However, it is not known whether fatty acids can modulate
      the activation of TLR2 or other TLRs for which respective ligands do not require
      acylated fatty acids. A saturated fatty acid, lauric acid, induced NFkappaB
      activation when TLR2 was co-transfected with TLR1 or TLR6 in 293T cells, but not
      when TLR1, 2, 3, 5, 6, or 9 was transfected individually. An n-3 polyunsaturated
      fatty acid (docosahexaenoic acid (DHA)) suppressed NFkappaB activation and
      cyclooxygenase-2 expression induced by the agonist for TLR2, 3, 4, 5, or 9 in a
      macrophage cell line (RAW264.7). Because dimerization is considered one of the
      potential mechanisms for the activation of TLR2 and TLR4, we determined whether
      the fatty acids modulate the dimerization. However, neither lauric acid nor DHA
      affected the heterodimerization of TLR2 with TLR6 as well as the homodimerization
      of TLR4 as determined by co-immunoprecipitation assays in 293T cells in which
      these TLRs were transiently overexpressed. Together, these results demonstrate
      that lauric acid activates TLR2 dimers as well as TLR4 for which respective
      bacterial agonists require acylated fatty acids, whereas DHA inhibits the
      activation of all TLRs tested. Thus, responsiveness of different cell types and
      tissues to saturated fatty acids would depend on the expression of TLR4 or TLR2
      with either TLR1 or TLR6. These results also suggest that inflammatory responses
      induced by the activation of TLRs can be differentially modulated by types of
      dietary fatty acids.

PMID- 14966135
TI  - Cholesterol-independent interactions with CD47 enhance alphavbeta3 avidity.
AB  - Expression in OV10 cells of either wild-type CD47 or its extracellular IgV domain
      linked to a glycosylphosphatidylinositol anchor-(IgV-GPI) enhanced ligand-induced
      alpha(v)beta(3) activation as detected by the binding of LIBS1 and LIBS6 mAbs.
      The amplitude of LIBS binding was greater with both CD47 and IgV-GPI expression,
      indicating an increase in the population of "activable" integrin molecules.
      Expression of either CD47 species also increased alpha(v)beta(3)-mediated
      adhesion to vitronectin, and to surfaces coated with the anti-beta(3) antibody
      AP3, because of enhanced clustering of alpha(v)beta(3) as confirmed by chemical
      cross-linking. Cholesterol depletion with methyl-beta-cyclodextrin did not
      prevent the increase in anti-LIBS binding, but reduced cell adhesion to
      vitronectin and AP3. However, cells expressing CD47 were partially insulated
      against this disruption, and IgV-GPI was even more effective. Both CD47 and IgV
      GPI were found in cholesterol-rich rafts prepared in the absence of detergent,
      but only CD47 could recruit alpha(v)beta(3) and its associated signaling
      molecules to these domains. Thus CD47-alpha(v)beta(3) complexes in cholesterol
      rich raft domains appear to engage in G(i)-dependent signaling whereas CD47
      alpha(v)beta(3) interactions that lead to integrin clustering are also detergent
      resistant, but are insensitive to cholesterol depletion and do not require the
      transmembrane region of CD47.

PMID- 14966136
TI  - CD81 associates with 14-3-3 in a redox-regulated palmitoylation-dependent manner.
AB  - As a member of the tetraspanin superfamily of proteins, CD81 has been linked to a
      number of biologic functions including cellular proliferation, differentiation,
      activation, and degranulation. As a co-receptor for hepatitis C virus, and a
      requirement for hepatocytes for infectivity of human Plasmodium falciparum and
      rodent P. yoelii sporozoite infectivity, CD81 may also play a vital role in
      pathology. Despite the importance of CD81 in multiple cellular functions, the
      molecular mechanism of action of CD81 in these processes has remained elusive.
      Here we report an association between CD81 and the epsilon isoform of 14-3-3, a
      serine/threonine-binding intracellular signaling protein. Furthermore, we provide
      evidence that in human, this association is influenced by the palmitoylation
      state of the CD81 cytoplasmic tails. We have generated a series of CD81 cysteine
      mutants to identify palmitoylated intracellular motifs of CD81, and reveal
      palmitoylation on the N- and C-terminal tails as well as the intracellular loop
      between transmembrane domains 2 and 3. One of these mutants lacks all five of its
      intracellular cysteines and therefore cannot be palmitoylated. This
      unpalmitoylated version of CD81 shows constitutive association with 14-3-3.
      Interestingly, we find that under oxidative conditions, CD81 palmitoylation is
      inhibited and that condition correlates with the association of CD81 and 14-3-3.
      These finding suggest that CD81 signaling events could be mediated by 14-3-3
      adapter proteins, and these signals may be dependent on cellular redox.

PMID- 14966137
TI  - 73-kDa molecular chaperone HSP73 is a direct target of antibiotic gentamicin.
AB  - Although gentamicin (GM) has been used widely as an antibiotic, the specific
      binding protein of the drug has not yet been understood sufficiently. Here we
      show that GM specifically associates with the 73-kDa molecular chaperone HSP73
      and reduces its chaperone activity in vitro. In the present study, we
      investigated GM-specific binding proteins using a GM-affinity column and porcine
      kidney cytosol. After washing the column, only the 73-kDa protein was eluted from
      the column by the addition of 10 mm GM. None of the other proteins were found in
      the eluant. Upon immunoblotting, the protein was identical to HSP73. Upon CD
      spectrum analysis, the binding of GM to HSP73 resulted in a conformational change
      in the protein. Although HSP73 prevents aggregation of unfolded rhodanese in
      vitro, the chaperone activity of HSP73 was suppressed in the presence of GM.
      Using limited proteolysis of HSP73 by TPCK-trypsin, the GM binding site is a COOH
      terminal for one third of the protein known to be a peptide-binding domain.
      During immunohistochemistry, HSP73 and GM were co-localized in enlarged lysosomes
      of rat kidneys with GM-induced acute tubular injury in vivo. Our results suggest
      that the specific association between HSP73 and GM may reduce the chaperone
      activity of HSP73 in vitro and/or in vivo, and this may have an interaction with
      GM toxicity in kidneys with GM-induced acute tubular injury.

PMID- 14966138
TI  - Intracellular phosphate serves as a signal for the regulation of the PHO pathway
      in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, the phosphate signal transduction pathway (PHO
      pathway) is known to regulate the expression of several phosphate-responsive
      genes, such as PHO5 and PHO84. However, the fundamental issue of whether cells
      sense intracellular or extracellular phosphate remains unresolved. To address
      this issue, we have directly measured intracellular phosphate concentrations by
      (31)P NMR spectroscopy. We find that PHO5 expression is strongly correlated with
      the levels of both intracellular orthophosphate and intracellular polyphosphate
      and that the signaling defect in the Deltapho84 strain is likely to result from
      insufficient intracellular phosphate caused by a defect in phosphate uptake.
      Furthermore, the Deltaphm1Deltaphm2, Deltaphm3, and Deltaphm4 strains, which lack
      intracellular polyphosphate, have higher intracellular orthophosphate levels and
      lower expression of PHO5 than the wild-type strain. By contrast, the Deltaphm5
      strain, which has lower intracellular orthophosphate and higher polyphosphate
      levels than the wild-type strain, shows repressed expression of PHO5, similar to
      the wild-type strain. These observations suggest that PHO5 expression is under
      the regulation of intracellular orthophosphate, although orthophosphate is not
      the sole signaling molecule. Moreover, the disruption of PHM3, PHM4, or of both
      PHM1 and PHM2 in the Deltapho84 strain suppresses, although not completely, the
      PHO5 constitutive phenotype by increasing intracellular orthophosphate,
      suggesting that Pho84p affects phosphate signaling largely by functioning as a
      transporter.

PMID- 14966139
TI  - A single amino acid determinant governs the species-specific sensitivity of
      APOBEC3G to Vif action.
AB  - APOBEC3G (also known as CEM15) is an innate intracellular antiretroviral factor
      that is counteracted by the Vif protein of lentiviruses. While APOBEC3G
      orthologues from several species are active against a broad range of
      retroviruses, given Vif proteins have a narrow spectrum of activity. For
      instance, HIV-1 Vif efficiently blocks APOBEC3G from human but not African green
      monkey (AGM), whereas the reverse is observed with SIV(AGM) Vif. Here, we
      demonstrate that a single amino acid at position 128 of human and AGM APOBEC3G
      governs the virus-specific sensitivity of these proteins to Vif-mediated
      inhibition. Furthermore, we show that this phenotype correlates with the ability
      of Vif to bind APOBEC3G and interfere with its incorporation into virions. These
      results shed light on an important determinant of the tropism of primate
      lentiviruses.

PMID- 14966140
TI  - Functional identification of SLC5A8, a tumor suppressor down-regulated in colon
      cancer, as a Na(+)-coupled transporter for short-chain fatty acids.
AB  - SLC5A8, a tumor suppressor gene down-regulated in human colon cancer, codes for a
      transporter in the Na(+)/glucose cotransporter gene family, but the definitive
      functional identity of the transporter protein is not known. Since this gene is
      expressed abundantly in the colon where short-chain fatty acids are generated by
      bacterial fermentation, we tested the hypothesis that it codes for a Na(+)
      coupled transporter for these fatty acids. The coding region of SLC5A8 mRNA was
      amplified from human intestine and expressed heterologously in Xenopus laevis
      oocytes. Transport function was monitored by uptake of radiolabeled substrates
      and by substrate-induced currents under voltage-clamp conditions. Uptake of short
      chain fatty acids (lactate, pyruvate, acetate, propionate, and butyrate) in
      oocytes expressing SLC5A8 was severalfold higher than in uninjected oocytes.
      Exposure of SLC5A8-expressing oocytes to these fatty acids induced inward
      currents under voltage-clamp conditions in a Na(+)-dependent manner. These
      currents were saturable and the substrate concentrations needed for half-maximal
      induction of the current were in the range of 0.08-2.5 mm. The substrate-induced
      currents decreased as the carbon chain length of the substrates increased. The
      Na(+)-activation kinetics indicated involvement of more than one Na(+) ion in the
      activation process. Direct measurements of substrate (propionate) and charge
      transfer showed that three positive charges are transferred into oocytes per
      substrate molecule. These studies establish the functional identity of SLC5A8 as
      a Na(+)-coupled transporter for short-chain fatty acids.

PMID- 14966141
TI  - Mitogen-activated protein kinase kinase kinase kinase 4 as a putative effector of
      Rap2 to activate the c-Jun N-terminal kinase.
AB  - Little is known about the specific signaling roles of Rap2, a Ras family small
      GTP-binding protein. In a search for novel Rap2-interacting proteins by the yeast
      two-hybrid system, we isolated isoform 3 of the human mitogen-activated protein
      kinase kinase kinase kinase 4 (MAP4K4), a previously described but
      uncharacterized isoform. Other isoforms of MAP4K4 in humans and mice are known as
      hematopoietic progenitor kinase (HPK)/germinal center kinase (GCK)-like kinase
      and Nck-interacting kinase, respectively. MAP4K4 belongs to the STE20 group of
      protein kinases and regulates c-Jun N-terminal kinase (JNK). MAP4K4 interacted
      with Rap2 through its C-terminal citron homology domain but did not interact with
      Rap1 or Ras. Interaction with Rap2 required the intact effector region of Rap2.
      MAP4K4 interacted preferentially with GTP-bound Rap2 over GDP-bound Rap2 in
      vitro. In cultured cells, MAP4K4 colocalized with Rap2, while a mutant MAP4K4
      lacking the citron homology domain failed to do so. Furthermore, Rap2 enhanced
      MAP4K4-induced activation of JNK. These results suggest that MAP4K4 is a putative
      effector of Rap2 mediating the activation of JNK by Rap2.

PMID- 14966142
TI  - Reducing mortality: an important aim of epilepsy management.

PMID- 14966143
TI  - Predicting functional outcome in acute stroke--prognostic models and clinical
      judgement.

PMID- 14966144
TI  - Early pathological changes in the parkinsonian brain.

PMID- 14966145
TI  - Cerebral perfusion and stroke.
AB  - Stroke is a heterogeneous syndrome caused by multiple disease mechanisms, but all
      result in a disruption of cerebral blood flow with subsequent tissue damage. This
      review covers the mechanisms responsible for regulation of the normal cerebral
      circulation, and how they are disrupted in disease states. A central concept in
      treating patients with acute ischaemic stroke is the existence of an ischaemic
      penumbra of potentially salvageable tissue, and the evidence for its existence in
      humans is reviewed.

PMID- 14966146
TI  - Delirium.
AB  - Delirium is a common cause of mortality and morbidity in older people in
      hospital, and indicates severe illness in younger patients. Identification of
      risk factors, education of professional carers, and a systematic approach to
      management can improve the outcome of the syndrome. Physicians should be aware
      that delirium sufferers often have an awareness of their experience, which may be
      belied by their varying grasp of reality.

PMID- 14966147
TI  - Idiopathic recurrent stupor: a warning.
AB  - A proposal that an endogenous benzodiazepine-like agent named endozepine-4 might
      be responsible for presentations of recurrent stupor has gained wide acceptance.
      A case of recurrent stupor over two decades is presented with many similarities
      to previous cases of "endozepine stupor". This case, however, was caused by
      exogenous benzodiazepine administration and serves as a warning to clinicians to
      beware of this diagnosis.

PMID- 14966149
TI  - Brain metabolic decreases related to the dose of the ApoE e4 allele in
      Alzheimer's disease.
AB  - OBJECTIVES: Declines in brain glucose metabolism have been described early in
      Alzheimer's disease (AD), and there is evidence that a genetic predisposition to
      AD contributes to accelerate this process. The epsilon 4 (e4) allele of the
      apolipoprotein E (ApoE) gene has been implicated as a major risk factor in this
      process. The aim of this FDG-PET study was to assess the ApoE e4 dose related
      effect on regional cerebral glucose metabolism (METglc) in clinical AD patients,
      with statistical voxel based methods. METHODS: Eighty six consecutive mild to
      moderate AD patients included in the Network for Efficiency and Standardisation
      of Dementia Diagnosis database underwent FDG-PET scans at rest. PCR was used to
      determine the ApoE genotype. Patients were grouped as e4 non-carriers (n = 46),
      e3/e4 (n = 27) and e4/e4 (n = 13) carriers. A voxel-based mapping program was
      used to compare each AD subgroup with a database of 35 sex and age matched
      controls (p<0.001, corrected for cluster extent) and also to compare between the
      subgroups (p<0.001, uncorrected). RESULTS: No difference was found as to age at
      examination, age at onset, sex, disease duration, educational level, or severity
      of dementia between AD subgroups. Compared with controls, all AD subgroups had
      equivalent METglc reductions in the precuneus, posterior cingulate,
      parietotemporal, and frontal regions. Direct comparisons between AD subgroups
      indicated that patients with at least one e4 allele had METglc reductions within
      additional associative and limbic areas compared with e4 non-carriers.
      CONCLUSIONS: The present FDG-PET study showed different metabolic phenotypes
      related to the ApoE genotype in clinical AD patients, as revealed with voxel
      based statistical methods. The results suggest a generalised disorder in e4
      carriers impairing metabolism globally, in addition to the more localised changes
      typical of AD patients.

PMID- 14966150
TI  - Association study of Notch 4 polymorphisms with Alzheimer's disease.
AB  - BACKGROUND: The NOTCH4 gene is located at 6p21.3, a site shown in several studies
      to have significant linkage with Alzheimer's disease. OBJECTIVE: To investigate
      the potential impact of two polymorphisms within this gene on the risk of
      developing Alzheimer's disease. METHODS: Genotyping of promoter and 5'-UTR
      polymorphisms was done in Scottish, English, and French populations. The
      potential functionality of the 5'-UTR polymorphism was assessed by testing its
      impact on A beta load in Alzheimer brains and also by undertaking electrophoretic
      mobility shift assays and transfection experiments. RESULTS: No association of
      the Notch4 polymorphisms alone with the disease was observed in any of the
      populations. However, an interaction of the 5'-UTR C/T polymorphism with the
      epsilon 4 allele of the APOE gene was detected in United Kingdom populations but
      not in the French. No relation between the 5'-UTR polymorphism and A beta loads
      was detected overall or in the presence or absence of the epsilon 4 allele. No
      DNA protein specific binding was found with proteins from neuroblastoma, glioma,
      or astrocytoma cells, and no allele dependent transcriptional activity was
      detected. CONCLUSIONS: No association between two NOTCH4 polymorphisms alone and
      Alzheimer's disease was observed in the three populations, but there was evidence
      of an increased risk associated with the 5'-UTR CC genotype in epsilon 4 bearers
      in the United Kingdom. As no functionality for this polymorphism could be
      determined, it is likely that the interaction is spurious or results from a
      linkage disequilibrium of this 5'-UTR polymorphism with another marker elsewhere
      in the 6p21.3 locus.

PMID- 14966151
TI  - Silas Weir Mitchell and the "rest cure".

PMID- 14966152
TI  - Fluctuating cognition in dementia with Lewy bodies and Alzheimer's disease is
      qualitatively distinct.
AB  - OBJECTIVES: To document and illustrate qualitative features of fluctuating
      cognition as described by care givers of patients with probable dementia with
      Lewy bodies (DLB) and Alzheimer's disease (AD). To determine whether the quality
      of the fluctuations differs between DLB and AD. To examine the clinical utility
      of two recently developed rating scales. METHODS: Care givers of 13 patients with
      early probable DLB and 12 patients with early probable AD were interviewed using
      the Clinician Assessment of Fluctuation and the One Day Fluctuation Assessment
      Scale, both developed recently. Descriptions of fluctuating cognition were
      recorded verbatim, analysed, and rated. RESULTS: Descriptions of fluctuating
      cognition in DLB had a spontaneous, periodic, transient quality, which appeared
      to reflect an interruption in the ongoing flow of awareness or attention that
      impacted on functional abilities. Descriptions of fluctuations in AD frequently
      highlighted episodes of memory failure, or a more enduring state shift in the
      form of "good" and "bad" days, typically occurring in response to the cognitive
      demands of the immediate environment. These qualitative differences could be
      detected reliably by independent raters, but were not always captured in standard
      severity scores. CONCLUSION: Fluctuations occurring in DLB have particular
      characteristics that are distinguishable from fluctuations occurring in AD.
      Interpretation and application of the fluctuation criterion continues to limit
      the diagnostic sensitivity of the consensus criteria for DLB. Findings suggest
      that explicit documentation and a wider appreciation of these distinctions could
      improve the reliability with which less experienced clinicians identify this core
      diagnostic feature in the clinical setting.

PMID- 14966153
TI  - A short scale for the assessment of motor impairments and disabilities in
      Parkinson's disease: the SPES/SCOPA.
AB  - OBJECTIVES: To evaluate the reliability and validity of the Short Parkinson's
      Evaluation Scale (SPES)/SCales for Outcomes in Parkinson's disease (SCOPA)-a
      short scale developed to assess motor function in patients with Parkinson's
      disease (PD). METHODS: Eighty five patients with PD were assessed with the
      SPES/SCOPA, Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr
      (H&Y) scale, and Schwab and England (S&E) scale. Thirty four patients were
      examined twice by two different assessors who were blinded to each other's scores
      and test executions. Additionally, six items of the motor section of the
      SPES/SCOPA were assessed in nine patients and recorded on videotape to evaluate
      inter-rater and intra-rater reliability. RESULTS: The reproducibility of the sum
      scores in the clinical assessments was high for all subscales of the SPES/SCOPA.
      Inter-rater reliability coefficients for individual items ranged from 0.27-0.83
      in the motor impairment section, from 0.58-0.82 in the activities of daily living
      section, and from 0.65-0.92 in the motor complications section. Inter-rater
      reliability of the motor items in the video assessments ranged from 0.70-0.87 and
      intra-rater reliability ranged from 0.81-0.95. The correlation between related
      subscales of the SPES/SCOPA and UPDRS were all higher than 0.85, and both scales
      revealed similar correlations with other measures of disease severity. The mean
      time to complete the scales differed significantly (p<0.001) and measured 8.1 (SD
      1.9) minutes for the SPES/SCOPA and 15.6 (SD 3.6) minutes for the UPDRS.
      CONCLUSION: The SPES/SCOPA is a short, reliable, and valid scale that can
      adequately be used in both research and clinical practice.

PMID- 14966154
TI  - Use and interpretation of on/off diaries in Parkinson's disease.
AB  - OBJECTIVE: To explore the use and interpretation of self reported on/off diary
      data for assessment of daily motor fluctuations in Parkinson's disease. METHODS:
      26 consecutive non-demented patients with fluctuating Parkinson's disease
      received standardised training on how to fill out the four category CAPSIT-PD
      on/off diary, followed by four hours of clinical observation and four weeks of
      daytime on/off diaries every 30 minutes at home. RESULTS: Overall patient
      clinician agreement in diary entries was good (kappa = 0.62; weighted kappa =
      0.84). Agreement for individual diary categories was good for "off" and "on with
      dyskinesias" (kappa = > or =0.72), but moderate for "partial off" and "on" (kappa
      = 0.49). The overall validity of patient kept diaries was supported by expected
      symptom severity variability across diary categories, as assessed in the clinic.
      One day's home diary data failed to predict outcomes from the full four weeks for
      all diary categories, and data from three days failed to yield good prediction
      (predefined as R(2) = > or =approximately 0.7) for the time spent in "off" and
      "partial off". Data from one week yielded good prediction (R(2) = > or =0.74) in
      all instances except "partial off", which could not be well predicted even when
      two weeks' home diary data were considered (R(2) = 0.52). CONCLUSIONS: The data
      provide support for the overall accuracy and validity of the four category CAPSIT
      PD on/off diary, but suggest that a three category diary format may improve
      accuracy and validity. Interpretation of diary data beyond the assessed time
      frame should be made with caution unless diaries have been kept for sufficiently
      long periods.

PMID- 14966155
TI  - Predicting functional outcome in acute stroke: comparison of a simple six
      variable model with other predictive systems and informal clinical prediction.
AB  - BACKGROUND: Statistical models that predict functional outcome after stroke using
      six simple variables (SSV) have recently been developed and validated. OBJECTIVE:
      To compare the accuracy of these models with other simple ways of predicting
      outcome soon after stroke. METHODS: The SSV model for being alive and independent
      (modified Rankin score < or =2) six months or one year after stroke was compared
      with predictions based on a model that included only age and Oxford community
      stroke project classification, with predictions based on conscious level and
      urinary continence, and with informal clinical predictions made by clinicians
      interested in stroke. Predictions were compared in an independent hospital based
      cohort of stroke patients using receiver operator characteristic (ROC) curves.
      RESULTS: The SSV model at six months had a significantly greater area under the
      curve (0.84) than the model with only age and stroke classification (0.75).
      Predictions based on conscious level and urinary continence were no better than
      those of the SSV model and were unable to predict subjects with a high
      probability of good outcome. The sensitivity and specificity for informal
      clinical predictions at one year lay on or below the SSV model curve, implying
      that the SSV model was at least as good as clinical predictions. CONCLUSIONS: The
      SSV models performed as well as or better than other simple predictive systems.
      These models will be useful in epidemiological studies but should not be used to
      guide clinical management until their impact on patient care and outcome has been
      evaluated.

PMID- 14966156
TI  - Provision of 24 hour acute neurology care by neurologists: manpower requirements
      in the UK.
AB  - OBJECTIVES: The ABN has published standards of care for patients with acute
      neurological disease. Derriford Hospital provides a 24 hour neurology intake
      service to a population of 500,000 with the equivalent of four consultants, three
      specialist registrars (SpRs), and four senior house officers (SHOs) with a 37 bed
      ward. The authors undertook a prospective study of all neurology admissions to
      enable calculation of manpower necessary to meet the ABN guidelines. METHODS: All
      admissions to the neurology department were analysed prospectively for a three
      month period (March to May 2002). RESULTS: There were 629 admissions (equating to
      2500 per year); data were collected for 93%. 78% of admissions were emergency,
      16% elective. The mean number of neurology inpatients at any time was 76, with
      three (4%) being elective. The main diagnostic categories were stroke (29%),
      headache syndrome (13%), and epilepsy or seizures (12%). With regard to emergency
      admissions, 94% were seen by a neurology SHO within 6 hours and 81% by an SpR or
      consultant within 24 hours. Twenty five percent of emergency admissions were not
      seen by a consultant. 55% of patients were cared for on non-neurological wards
      for their entire admission. Median length of stay for stroke patients was 9.5
      days, compared with 4 days for other patients. 37% of patients received a
      neurology follow up appointment. Currently each SpR spends 18 hours per week
      involved in the care of acute neurology admissions. CONCLUSION: Meeting the ABN
      guidelines will require an increase in total neurology bed provision to at least
      15 per 100,000 population, with the equivalent of 3 consultant sessions (11
      hours/week). Meeting the European Working Time Directive will require a minimum
      of 8-10 SpRs working a full shift system, which will have a significant impact on
      training and other aspects of service delivery.

PMID- 14966157
TI  - Prospective validation of a proposal for diagnosis and management of patients
      attending the emergency department for mild head injury.
AB  - BACKGROUND: In mild head injury, predictors to select patients for computed
      tomography (CT) and/or to plan proper management are needed. The strength of
      evidence of published recommendations is insufficient for current use. We
      assessed the diagnostic accuracy and the clinical validity of the proposal of the
      Neurotraumatology Committee of the World Federation of Neurosurgical Societies on
      mild head injury from an emergency department perspective. METHODS: In a three
      year period, 5578 adolescent and adult subjects were prospectively recruited and
      managed according to the proposed protocol. Outcome measures were: (a) any post
      traumatic lesion; (b) need for neurosurgical intervention; (c) unfavourable
      outcome (death, permanent vegetative state or severe disability) after six
      months. The predictive value of a model based on five variables (Glasgow coma
      score, clinical findings, risk factors, neurological deficits, and skull
      fracture) was tested by logistic regression analysis. FINDINGS: At first CT
      evaluation 327 patients (5.9%) had intracranial post-traumatic lesions. In 16
      cases (0.3%) previously undiagnosed lesions were detected after re-evaluation
      within seven days. Neurosurgical intervention was needed in 71 patients (1.3%)
      and an unfavourable outcome occurred in 39 cases (0.7%). The area under the ROC
      curve of the variables in predicting post-traumatic lesions was 0.906 (0.009)
      (sensitivity 70.0%, specificity 94.1% at best cut off), neurosurgical
      intervention was 0.926 (0.016) (sensitivity 81.7%, specificity 94.1%), and
      unfavourable outcome was 0.953 (0.014) (sensitivity 88.1%, specificity 95.1%).
      INTERPRETATION: The variables prove highly accurate in the prediction of
      clinically meaningful outcomes, when applied to a consecutive set of patients
      with mild head injury in the clinical setting of a 1st level emergency
      department.

PMID- 14966158
TI  - Neurophysiological testing correlates with clinical examination according to
      fibre type involvement and severity in sensory neuropathy.
AB  - OBJECTIVE: To investigate a comprehensive battery of neurophysiological tests for
      objective evaluation of sensory neuropathies including fibre type involvement and
      severity, and to determine the relation between neurophysiological data and
      clinical examination. METHODS: 45 patients referred for sensory neuropathy were
      studied using a standardised clinical evaluation of large and small fibre
      symptoms and an original neurophysiological battery. Clinical evaluation
      included: assessment of tactile, vibratory, and pin sensation; tendon reflexes;
      toe position sense; ataxia score; pain level; and presence of trophic, vasomotor,
      or sudomotor abnormalities. The neurophysiological battery included: recording of
      large fibre and small fibre components of the sural sensory nerve action
      potential; somatosensory evoked cortical potentials and soleus H reflex following
      tibial nerve electrical stimulation; laser evoked potentials following Nd:YAG
      laser stimulation of the foot; and plantar sympathetic skin response to median
      nerve stimulation. Neuropathy was classified according to the predominantly
      affected fibre type, and a severity score was established based on clinical and
      neurophysiological abnormalities. RESULTS: On clinical examination there were 22
      patients with large fibre sensory neuropathy (LFSN), 18 with mixed sensory
      neuropathy (MSN), and five with small fibre sensory neuropathy (SFSN).
      Neurophysiological classification identified 25 patients with LFSN, 13 with MSN,
      and seven with SFSN. Clinical and neurophysiological classifications and severity
      scores were correlated, whatever the type of neuropathy. CONCLUSIONS: The
      correlation between clinical examination and the results of an original
      neurophysiological test battery offers a comprehensive clinical and
      neurophysiological approach to the objective assessment of peripheral
      neuropathies according to fibre type involvement and overall severity.

PMID- 14966159
TI  - Comparative analysis of the spatial distribution and severity of cerebral
      microbleeds and old lacunes.
AB  - BACKGROUND: Cerebral microbleeds, which result from microangiopathic changes
      following chronic hypertension, may reflect bleeding-prone microangiopathy.
      However, the distribution of these lesions has not been compared with that of
      lacunes, which represent occlusive type microangiopathy. OBJECTIVES: To compare
      the cerebral distribution of microbleeds and lacunes and correlate their
      severity. METHODS: The study population comprised 129 hypertensive patients who
      underwent brain magnetic resonance imaging (MRI), including gradient echo (GE)
      sequences. Cerebral microbleeds were counted using GE-MRI data, and lacunes were
      also counted by comparing T1 and T2 weighted MRI. To investigate the
      distributions, the number of patients with each type of lesion was compared, and
      the occurrence index (the total number of the specific lesions divided by the
      total number of patients) was examined statistically. Correlation analyses were
      done on the relations between the different grades of microbleeds, lacunes, and
      leukoaraiosis. RESULTS: Cerebral microbleeds and lacunes were found at various
      foci in the brain, with a preference for the cortico-subcortical region and the
      deep grey matter. The occurrence index of microbleeds, but not of lacunes, was
      significantly higher in the cortico-subcortical region than in the deep grey
      matter. The severity of the microbleeds was positively correlated with the
      severity of lacunes, and both types of lesion were closely correlated with the
      degree of leukoaraiosis. CONCLUSIONS: These data suggest that microbleeds and
      lacunes tend to occur to a similar extent in long standing hypertension, but not
      necessarily in the same locations.

PMID- 14966160
TI  - Unilateral posterior parietal lobe lesions disrupt kinaesthetic representation of
      forearm orientation.
AB  - OBJECTIVE: To apply the lesion method to assess neuroanatomical substrates for
      judgments of forearm orientation from proprioceptive cues in humans. METHODS:
      Participants were 15 subjects with chronic unilateral brain lesions and stable
      behavioural deficits, and 14 neurologically normal controls. Subjects aligned the
      forearm to earth fixed vertical and trunk fixed anterior-posterior (A-P) axes
      ("straight ahead"), with the head aligned to the trunk and with head and shoulder
      orientations varied on each trial. RESULTS: Most subjects with posterior parietal
      lobe lesions made larger variable errors than controls in aligning the forearm to
      the earth fixed vertical axis and the trunk A-P axes, whether the head was held
      upright or oriented in different positions. Lesion subjects and controls made
      similar constant errors for aligning the forearm to gravitational vertical.
      Variable error magnitude correlated positively with greater lesion volume of
      right and left superior parietal lobules (SPL), but not with lesions in other
      brain areas. Larger variable errors for aligning the forearm to the trunk fixed A
      P axis were also correlated with the volume of SPL lesions, but constant error
      magnitude correlated with larger volume lesions in premotor areas, inferior
      parietal lobules, and posterior regions of the superior temporal gyri, but not
      with SPL lesion volume. CONCLUSIONS: The findings suggest that the right and left
      superior and inferior parietal lobules, posterior superior temporal gyri, and
      premotor areas play a role in defining higher level coordinate systems for
      specifying orientation of the right and left forearm.

PMID- 14966161
TI  - Acute ophthalmoparesis in the anti-GQ1b antibody syndrome: electrophysiological
      evidence of neuromuscular transmission defect in the orbicularis oculi.
AB  - OBJECTIVE: To prospectively study anti-GQ1b antibody positive cases of acute
      ophthalmoparesis (AO) clinically and electrophysiologically. METHODS: Nine
      consecutive cases presenting with predominantly acute ophthalmoplegia were
      assessed clinically and had stimulated single fibre electromyography (SFEMG) of
      the orbicularis oculi at presentation. All had magnetic resonance imaging brain
      scans and anti-GQ1b antibody titres determined. RESULTS: Four cases had elevated
      anti-GQ1b antibody titres and abnormal SFEMG studies, which improved in tandem
      with clinical recovery over three months. Five other anti-GQ1b antibody negative
      cases were diagnosed as diabetic related cranial neuropathy, idiopathic cranial
      neuropathy, ocular myasthenia gravis, and Tolosa-Hunt syndrome. All five cases
      showed complete recovery over a three month period. CONCLUSIONS: This study
      demonstrated electrophysiologically the dynamic improvement of neuromuscular
      transmission of anti-GQ1b antibody positive cases of AO, in tandem with clinical
      recovery. SFEMG is of value in differentiating weakness due to neuromuscular
      transmission defect from neuropathy in these clinical situations.

PMID- 14966162
TI  - Diffusion tensor MRI correlates with executive dysfunction in patients with
      ischaemic leukoaraiosis.
AB  - BACKGROUND: Cerebral small vessel disease is a common cause of vascular dementia.
      Both discrete lacunar infarcts and more diffuse ischaemic changes, seen as
      confluent high signal (leukoaraiosis) on T2 weighted magnetic resonance imaging
      (MRI), occur. However, there is a weak correlation between T2 lesion load and
      cognitive impairment. Diffusion tensor MRI (DTI) is a new technique that may
      provide a better index of white matter damage. OBJECTIVES: To determine whether
      DTI measures are correlated more strongly with cognitive performance than lesion
      load on T2 weighted images, and whether these correlations are independent of
      conventional MRI parameters. METHODS: 36 patients with ischaemic leukoaraiosis
      (leukoaraiosis plus a previous lacunar stroke) and 19 healthy volunteers
      underwent DTI, conventional MRI, and neuropsychological assessment. RESULTS: On
      DTI, diffusivity was increased both within lesions and in normal appearing white
      matter. Mean diffusivity of normal appearing white matter correlated with full
      scale IQ (r = -0.46, p = 0.009) and tests of executive function. These
      correlations remained significant after controlling for age, sex, brain volume,
      and T1/T2 lesion volumes. No significant correlation was identified between T2
      lesion load and IQ or neuropsychological scores. Of conventional measures, brain
      volume correlated best with cognitive function. CONCLUSIONS: Diffusion tensor
      measurements correlate better with cognition than conventional MRI measures. They
      may be useful in monitoring disease progression and as a surrogate marker for
      treatment trials. The findings support the role of white matter damage and
      disruption of white matter connections in the pathogenesis of cognitive
      impairment in cerebral small vessel disease.

PMID- 14966163
TI  - Autosomal dominant cerebellar ataxia: SCA2 is the most frequent mutation in
      eastern India.
AB  - OBJECTIVE: Spinocerebellar ataxia type 2 (SCA2) has been reported as the
      commonest dominant hereditary ataxia in India. However, India is an ethnically
      and religiously diverse population. Previous studies have not clearly indicated
      exact ethnic and religious origins, and must therefore be interpreted with
      caution. The purpose of this study was to determine the prevalence of different
      SCA mutations in a relatively homogeneous population from eastern India. METHODS:
      We identified 28 families with autosomal dominant cerebellar ataxia from eastern
      India. Each underwent full clinical evaluation and were analysed for the presence
      of SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, and SCA17 mutations. In addition,
      haplotype analysis was carried out in seven of the 16 families with SCA2.
      RESULTS: Seven patients from four (14%) families were positive for an expansion
      in SCA1 and 26 patients from 16 (57%) families were positive for an expansion in
      SCA2. No mutations were detected in the remaining eight families (29%). Most of
      the SCA1 and SCA2 families were Hindu from the state of Bihar. Five out of 26
      SCA2 patients in this study did not have slow saccades. In addition, four of
      seven SCA1 patients had slow saccades. We found an association between the SCA2
      CAG repeat expansion and the 285 base pair (bp) allele of microsatellite marker
      D12S1672, and also data supportive of the association between the expansion and
      the 225 bp allele of D12S1333, which has been previously described. CONCLUSIONS:
      We conclude that (1) although slow ocular saccades are highly suggestive of SCA2,
      that they are not universal, nor are they exclusive to this disorder and (2) SCA2
      is likely to be the commonest dominant ataxia in eastern India, with further
      evidence for a founder effect.

PMID- 14966164
TI  - Removal of large acoustic neurinomas (vestibular schwannomas) by the retrosigmoid
      approach with no mortality and minimal morbidity.
AB  - OBJECTIVE: To evaluate the safety and efficacy of removing large acoustic
      neurinomas (> or =3 cm) by the retrosigmoid approach. METHODS: Large acoustic
      neurinomas (mean (SD), 4.1 (0.6) cm) were removed from 50 consecutive patients by
      the retrosigmoid suboccipital approach while monitoring the facial nerve using a
      facial stimulator-monitor. Excision began with the large extrameatal portion of
      the tumour, followed by removal of the intrameatal tumour, and then removal of
      the residual tumour in the extrameatal region just outside the porus acusticus.
      The last pieces of tumour were removed by sharp dissection from the facial nerve
      bidirectionally, and resected cautiously in a piecemeal fashion. RESULTS: There
      were no postoperative deaths. The tumour was removed completely in 43 of 50
      patients (86%). The facial nerve was anatomically preserved in 92% of the
      patients and 84% had excellent facial nerve function (House-Brackmann grade 1/2).
      One patient recovered useful hearing after tumour removal. Cerebrospinal fluid
      leak occurred in 4%, but there were no cases of meningitis. All but two patients
      (96%) had a good functional outcome. CONCLUSIONS: The method resulted in a high
      rate of functional facial nerve preservation, a low incidence of complications,
      and good functional outcomes, with no mortality and minimal morbidity. Very
      favourable results can be obtained using the retrosigmoid approach for the
      removal of large acoustic neurinomas.

PMID- 14966165
TI  - Spinocerebellar ataxia type 8 in Scotland: genetic and clinical features in seven
      unrelated cases and a review of published reports.
AB  - OBJECTIVES: To establish whether the DNA expansion linked to spinocerebellar
      ataxia type 8 (SCA 8) is associated with ataxia in Scotland; to clarify the range
      of associated clinical phenotypes; and to compare the findings with previous
      reports. METHODS: DNA was screened from 1190 anonymised controls, 137 subjects
      who had tested negative for Huntington's disease, 176 with schizophrenia, and 173
      with undiagnosed ataxia. Five unrelated ataxic patients with the SCA 8 expansion
      and a sixth identified subsequently had clinical and psychometric assessment; the
      clinical features were available in a seventh. A systematic search for other
      reports of SCA 8 was undertaken. RESULTS: Over 98% of SCA 8 CTA/CTG repeat
      lengths fell between 14 and 40. Repeat lengths over 91 were observed in three
      healthy controls (0.12%), two patients with suspected Huntington's disease
      (0.73%), and six ataxic subjects (1.74%; p<0.0005 v healthy controls). Repeat
      lengths over 100 occurred in five ataxic subjects but in only one control. All
      seven symptomatic subjects with the SCA 8 expansion had a cerebellar syndrome;
      four had upper motor neurone signs; and 5/6 assessed had cognitive complaints.
      There was personality change in two and mood disturbance in three. In published
      reports, SCA 8 repeat lengths over 91 occurred in approximately 0.5% of the
      healthy population but were over-represented among ataxic patients (3.4%;
      p<0.0001). The predominant clinical phenotype was cerebellar, with pyramidal
      signs in 50%, and neuropsychiatric features in some cases. CONCLUSIONS: SCA 8
      expansion is a risk factor for a cerebellar syndrome, often associated with upper
      motor neurone and neuropsychiatric features. The expansion occurs unexpectedly
      often in the general population.

PMID- 14966166
TI  - Cerebral motor control in patients with gliomas around the central sulcus studied
      with spatially filtered magnetoencephalography.
AB  - OBJECTIVE: Application of spatially filtered magnetoencephalography (MEG) to
      investigate changes in the mechanism of cerebral motor control in patients with
      tumours around the central sulcus. METHODS: MEG records were made during a
      repetitive hand grasping task in six patients with gliomas around the central
      sulcus and in four control subjects. Power decreases in the alpha (8-13 Hz), beta
      (13-30 Hz), and low gamma bands (30-50 Hz) during the motor tasks (event related
      desynchronisation, ERD) were analysed statistically with synthetic aperture
      magnetometry. The tomography of ERD was superimposed on the individual's magnetic
      resonance image. RESULTS: beta ERD was consistently localised to the
      contralateral primary sensorimotor cortex (MI/SI) in control subjects, whereas
      the alpha and low gamma ERD showed considerable intersubject variability. beta
      ERD in patients during non-affected side hand movement was also localised to the
      contralateral MI/SI, but exclusively to the ipsilateral hemisphere during
      affected side hand movement. CONCLUSIONS: The altered pattern of ERD in the
      patient group during affected side hand movement suggests recruitment of diverse
      motor areas, especially the ipsilateral MI/SI, which may be required for the
      effective movement of the affected hand.

PMID- 14966167
TI  - Saccade dysfunction associated with chronic petrol sniffing and lead
      encephalopathy.
AB  - BACKGROUND: In chronic petrol sniffers, recent exposure to high levels of leaded
      petrol may give rise to a lead encephalopathy characterised by tremor, chorea,
      ataxia, hyperreflexia, convulsive seizures, and death. Neurological abnormalities
      associated with lead encephalopathy involve the cortex, basal ganglia,
      cerebellum, and brain stem. OBJECTIVE: To use saccadic eye movement tasks as an
      experimental tool to determine which CNS changes are associated with chronic
      petrol sniffing and which with a history of lead encephalopathy, and to what
      extent these changes are reversible. METHODS: Saccade function was assessed in
      chronic petrol sniffers with a history of lead encephalopathy (encephalopathic
      sniffers), chronic petrol sniffers who had never suffered lead encephalopathy
      (chronic sniffers), individuals who had sniffed petrol in the past but had not
      done so for more than six months (ex-sniffers), and individuals who had never
      sniffed petrol (non-sniffers). RESULTS: Chronic sniffers showed increased latency
      of visually guided saccades and antisaccades and increased antisaccade errors
      which suggested cortical and basal ganglia dysfunction. These abnormalities
      returned to normal in ex-sniffers. Encephalopathic sniffers showed the same
      abnormalities as chronic sniffers but with greater severity and additional
      saccadic signs including dysmetria, gaze evoked nystagmus, and saccade slowing
      which usually indicate cerebellar and brain stem dysfunction. CONCLUSIONS:
      Chronic petrol abuse is associated with cortical and basal ganglia abnormalities
      that are at least partially recoverable with abstinence. Additional long term
      cerebellar and brain stem abnormalities are associated with lead encephalopathy.

PMID- 14966168
TI  - Cerebral metastasis of renal carcinoma mimicking venous haemorrhagic infarction.

PMID- 14966169
TI  - Association of polymorphisms in the Tau and Saitohin genes with Parkinson's
      disease.
AB  - BACKGROUND: The Saitohin gene has recently been identified in intron 9 of the Tau
      gene. Because an association between Parkinson's disease and Tau has been
      described, Saitohin represents a candidate gene for Parkinson's disease.
      OBJECTIVE: To test these two genes for their association with Parkinson's disease
      in a large community based case-control study. RESULTS: Cases (n = 208) were more
      often homozygotes for the Tau H1 haplotype than controls (n = 483; odds ratio
      (OR) = 1.71 (95% confidence interval, 1.20 to 2.43); p = 0.003), and the saitohin
      Q allele was in complete linkage disequilibrium with the H1 haplotype. This
      association was stronger among cases with Parkinson's disease onset below 65
      years (< or =65 years: OR = 2.52 (1.49 to 4.25); p<0.001) than among those with
      older onset (>65 years: OR = 1.20 (0.73 to 1.98); p<0.47). CONCLUSIONS: The data
      suggest that there is a functional polymorphism at this locus involved in
      Parkinson's disease.

PMID- 14966170
TI  - Early pathological changes in the parkinsonian brain demonstrated by diffusion
      tensor MRI.
AB  - OBJECTIVE: To determine whether the fractional anisotropy (FA) of magnetic
      resonance diffusion tensor imaging is decreased in the nigrostriatal projection
      in parkinsonian patients. METHODS: FA values were compared in the extrapyramidal
      system of 12 patients with Parkinson's disease and eight age matched normal
      controls. RESULTS: Patients with Parkinson's disease had significantly decreased
      FA in the region of interest along a line between the substantia nigra and the
      lower part of the putamen/caudate complex, in which most of the nigrostriatal
      dopaminergic neurones are included. Loss of FA in this region was obvious even
      during the early clinical stages of Parkinson's disease. CONCLUSIONS: Assuming
      that the loss of FA parallels the neuronal change in the brain, the results are
      consistent with the view that more than half the dopaminergic neurones in the
      nigrostriatal projection are lost before the onset of Parkinson's disease. Close
      comparison of FA in the basal ganglia may contribute to the early diagnosis of
      Parkinson's disease.

PMID- 14966171
TI  - MRI characteristics of sporadic CJD with valine homozygosity at codon 129 of the
      prion protein gene and PrPSc type 2 in Japan.
AB  - Two Japanese sporadic Creutzfeld-Jakob disease (sCJD) patients with valine
      homozygosity at codon 129 of the prion protein gene and protease-resistant prion
      protein (PrP(Sc)) type 2 (VV2) are described. In contrast with Western countries,
      this type of sCJD is very rare in Japan. In 123 sCJD cases, only two were
      recognised as VV2 by the Japanese CJD surveillance committee. The clinical
      symptoms and pathological findings of the patients were similar to those of
      European and US patients. The noteworthy finding of diffusion weighted MRI (DWI)
      was that an abnormal high intensity covered a wide range of the thalamus
      including the dorsomedial nucleus, the pulvinar, and the ventral anterior,
      lateral, and posterolateral nuclei. This thalamic pattern has not been recognised
      in sCJD with methionine homozygosity and PrP(Sc) type 1 (MM1) or
      methionine/valine heterozygosity and PrP(Sc) type 1 (MV1) which comprises the
      vast majority of sCJD. This finding may be characteristic to VV2 and may
      distinguish it from MM1, MV1, and variant CJD. DWI can provide a very important
      clue for the antemortem diagnosis of VV2 subjects.

PMID- 14966172
TI  - Ictal magnetoencephalographic study in a patient with ring 20 syndrome.
AB  - OBJECTIVE: To report the ictal magnetoencephalography (MEG) in a patient with
      ring chromosome 20 mosaicism, a rare chromosomal anomaly associated with
      intractable epilepsy. METHODS: MEG and simultaneous EEG were recorded with a 204
      channel whole head MEG system. Ten habitual seizures occurred during the
      acquisition, which was done twice. The equivalent current dipoles (ECDs) for
      ictal discharges on MEG were calculated using a single dipole model. The ECDs
      were superimposed on a magnetic resonance image. RESULTS: During the seizures,
      EEG showed prolonged bursts of 5-6 Hz high voltage slow waves with spike
      components, dominantly in the bilateral frontal region. MEG showed epileptiform
      discharges corresponding to the ictal EEG. Ictal discharges on MEG were dominant
      in the frontal area in the initial portion, and then spread in the bilateral
      temporal area in the middle of the seizure. ECDs obtained from the spikes of the
      initial portion were clustered in the medial frontal lobe. CONCLUSIONS: The
      source of the ictal MEG was localised in the medial frontal lobe. The findings
      suggest that the mechanism underlying epilepsy in this case might be similar to
      medial frontal lobe epilepsy. Ictal MEG is a valuable tool for detecting the site
      of seizure onset.

PMID- 14966173
TI  - A systematic review of Terson's syndrome: frequency and prognosis after
      subarachnoid haemorrhage.
AB  - OBJECTIVE: To review systematically the frequency and prognostic significance of
      vitreous haemorrhage in patients with subarachnoid haemorrhage (Terson's
      syndrome). METHODS: Papers relating to vitreous haemorrhage in patients with
      subarachnoid haemorrhage were retrieved. The only studies considered were those
      with at least 10 consecutive cases of subarachnoid haemorrhage with or without
      vitreous haemorrhage. The frequency of vitreous haemorrhage in such cases was
      calculated in prospective and retrospective studies. Mortality was compared in
      patients with and without Terson's syndrome. RESULTS: 154 papers were reviewed.
      Three prospective studies and six retrospective studies satisfied the inclusion
      criteria. Of 181 patients with subarachnoid haemorrhage assessed prospectively
      (mean age, 51.7 years), 24 (13%) had vitreous haemorrhage; among 1086
      retrospective records, 37 (3%) had documented vitreous haemorrhage (p<0.001).
      Patients with Terson's syndrome had higher Hunt and Hess grades than those
      without (mean grade, 3.6 v 2.6). Patients with Terson's syndrome were also more
      likely to die (13 of 30 (43%) v 31 of 342 (9%); odds ratio 4.8; p<0.001).
      CONCLUSIONS: Prospective studies show a higher frequency of Terson's syndrome
      than retrospective studies, suggesting that vitreous haemorrhage is not well
      documented. Vitreous haemorrhage is an adverse prognostic finding in patients
      with subarachnoid haemorrhage.

PMID- 14966174
TI  - Coexistent blepharospasm and hemifacial spasm: overlapping pathophysiologic
      mechanism?
AB  - BACKGROUND/AIM: Blepharospasm (BEB) and hemifacial spasm (HFS) appear to be
      distinct disorders. Clinical characteristics of coexistent BEB and HFS have not
      been examined. The aim of this study was to determine the prevalence, clinical,
      and imaging features of coexistent BEB among a cohort of HFS patients and
      controls. RESULTS: Among 665 study subjects, nine (5.5%) of the 164 consecutive
      HFS patients had coexistent BEB, significantly higher than age and gender matched
      controls (0/501, 0%) without neurological diseases (p<0.0001). The mean age of
      the nine patients was 61.4 (SD 9.9) (range 51-72), consisting of 88.9% women, and
      66.7% had left sided HFS, similar to HFS patients without BEB. Six (66.7%)
      reported BEB symptoms at a mean of 0.8 years after HFS onset, one before, and
      onset was undetermined in two patients. Advanced magnetic resonance imaging and
      angiography revealed neurovascular compression of the ipsilateral side of HFS,
      without any basal ganglia lesions. CONCLUSIONS: BEB occurred more frequently in
      HFS patients, suggesting changes in the brainstem blink reflex circuitry could
      play a modulatory role in certain at-risk individuals resulting in the
      coexistence of these movement disorders.

PMID- 14966175
TI  - The exercise test as a monitor of disease status in hypokalaemic periodic
      paralysis.
AB  - OBJECTIVE: To evaluate exercise test responses in hypokalaemic periodic paralysis
      (HPP), to determine its value as a diagnostic tool and the factors that could
      affect the responses. METHODS: 22 subjects were studied from two families with
      HPP caused by R528H mutation, four patients with thyrotoxic periodic paralysis,
      15 normal controls, and four controls with hyperthyroidism. All family members
      were submitted to clinical evaluation, electrophysiological exercise testing, and
      DNA analysis. Patients with thyrotoxic periodic paralysis had exercise tests
      before and after treatment of their hyperthyroidism. RESULTS: Abnormal responses
      to the exercise tests were obtained only in subjects with recent attacks of
      weakness. They were not correlated with genotype, as asymptomatic carriers were
      unaffected. Patients with thyrotoxic periodic paralysis showed pronounced
      impairment while they were hyperthyroid, but improved when they were euthyroid.
      One patient with HPP and chronic KCl use had an increase in amplitude potentials
      over approximately 20 minutes, possibly related to alteration of potassium
      homeostasis. CONCLUSIONS: The exercise test is a useful diagnostic test for
      periodic paralysis, but in the absence of recent weakness negative results must
      be viewed with caution. It has advantages over the DNA test in being a non
      invasive functional test that can provide insights into abnormalities of muscle
      excitability.

PMID- 14966176
TI  - Female preclinical presenilin-1 mutation carriers unaware of their genetic status
      have higher levels of depression than their non-mutation carrying kin.
AB  - OBJECTIVES: To study depressive symptoms in preclinical presenilin-1 (PS1)
      related Alzheimer's disease. METHODS: Participants were 33 Mexican women at risk
      for inheriting PS1 mutations who were not demented. They were interviewed,
      underwent cognitive testing, and completed the Beck depression inventory (BDI).
      PS1 mutation status was determined. Mean BDI scores were compared between PS1
      mutation carriers and non-carriers. The percentage of subjects who reported
      seeing a psychiatric professional, and the percentage complaining of memory loss
      were compared between groups. Regression analysis was used to determine whether
      mutation status predicted BDI scores after adjusting for age, education, mini
      mental state examination, and subjective memory function. RESULTS: PS1 mutation
      carriers (n = 17) scored significantly higher than non-carriers (n = 16) on the
      BDI (mean score, 14.4 v 6.5, p = 0.017); 24% of mutation carriers and 12.5% of
      non-carriers admitted having sought help from a psychiatric professional (NS).
      Mutation status remained a significant predictor of BDI scores after adjusting
      for potential covariates. Though not demented, mutation carriers tended to score
      lower than non-carriers on several neuropsychological tests. CONCLUSIONS:
      Depressive symptoms can occur early in the course of PS1 related Alzheimer's
      disease, at least in women. This supports the hypothesis that depression may
      occur as a direct result of the neuropathology underlying Alzheimer's disease.

PMID- 14966177
TI  - Spinocerebellar ataxia type 2 with glial cell cytoplasmic inclusions.
AB  - Glial cell cytoplasmic inclusions were identified in a case of spinocerebellar
      ataxia type 2. These have not been reported before. The inclusions were found in
      low frequency in the dentate nucleus, cerebellar white matter, pontine transverse
      fibres, and the inferior olivary nucleus. They were of variable size and shape
      and expressed ubiquitin, thus resembling glial cytoplasmic inclusions in multiple
      system atrophy. However, their immunohistochemical profile was different as they
      did not show immunoreactivity for either tau protein or alpha-synuclein. There
      was no evidence of expanded polyglutamine tracts in these inclusions, which also
      failed to label with silver stains. As in many other neurodegenerative diseases,
      in spinocerebellar ataxia type 2 there may be pathogenic contributions of glial
      cells other than the common astrogliotic response to neuronal damage.

PMID- 14966178
TI  - Etizolam and benzodiazepine induced blepharospasm.

PMID- 14966179
TI  - Use of prostacyclin (iloprost) in digital vasculitis secondary to
      meningococcaemia.

PMID- 14966180
TI  - Pure motor stroke with major involvement of the index finger.

PMID- 14966181
TI  - The effect of interferon beta-1a on spasticity in primary progressive multiple
      sclerosis.

PMID- 14966182
TI  - A breathtaking headache.

PMID- 14966183
TI  - Efficacy of methyprednisolone pulse therapy on neuroleptic malignant syndrome in
      Parkinson's disease.

PMID- 14966184
TI  - Ischaemic stroke in chagasic patients.

PMID- 14966185
TI  - Traumatic brain injury as a risk factor for Alzheimer's disease.

PMID- 14966186
TI  - Mesencephalic ischemia and Parkinson's disease.

PMID- 14966187
TI  - Relationship between stridor and sleep apnoea syndrome: is it as simple as that?

PMID- 14966188
TI  - The specificity of prescription patterns in secondary stroke prevention.

PMID- 14966189
TI  - T cells in the lung of patients with hypersensitivity pneumonitis accumulate in a
      clonal manner.
AB  - Hypersensitivity pneumonitis (HP) is characterized by an alveolitis sustained by
      CD8(+) T lymphocytes showing a limited expression of the T cell receptor (TCR).
      We previously demonstrated that a bias in T cell selection occurs in the lower
      respiratory tract of patients with HP, with a compartmentalization in the lung of
      CD8(+) T cells bearing (TCR)-beta variable (TCRBV) #2, 3, 5, 6, 8, and 13 gene
      segments. We herein characterized the clonal T cell populations present in the
      lung and in the blood of patients with HP. Heteroduplex analyses, cloning, and
      sequencing T cells bearing TCR indicate oligoclonal expansions of T cells
      expressing homologous or identical complementary-determining region 3.
      Furthermore, T cell clones isolated from the two compartments expressed similar,
      sometimes identical, junctional regions. Removal from antigenic exposure led to
      the disappearance of T cell clones. Our findings indicate that expansions of T
      lymphocytes bearing clonal TCRBV region gene segments take place in the lung of
      patients with HP during exposure. The evidence that identical T cell clones are
      present in the lung and the blood of the same patient suggests that the immune
      reaction occurring at lung level gives rise to a systemic reaction.

PMID- 14966190
TI  - Human B lymphoblastoid cells contain distinct patterns of cathepsin activity in
      endocytic compartments and regulate MHC class II transport in a cathepsin S
      independent manner.
AB  - Endocytic proteolysis represents a major functional component of the major
      histocompatibility complex class II antigen-presentation machinery. Although
      transport and assembly of class II molecules in the endocytic compartment are
      well characterized, we lack information about the pattern of endocytic protease
      activity along this pathway. Here, we used chemical tools that visualize
      endocytic proteases in an activity-dependent manner in combination with
      subcellular fractionation to dissect the subcellular distribution of the major
      cathepsins (Cat) CatS, CatB, CatH, CatD, CatC, and CatZ as well as the asparagine
      specific endoprotease (AEP) in human B-lymphoblastoid cells (BLC). Endocytic
      proteases were distributed in two distinct patterns: CatB and CatZ were most
      prominent in early and late endosomes but absent from lysosomes, and CatH, CatS,
      CatD, CatC, and AEP distributed between late endosomes and lysosomes, suggesting
      that CatB and CatZ might be involved in the initial proteolytic attack on a given
      antigen. The entire spectrum of protease activity colocalized with human
      leukocyte antigen-DM and the C-terminal and N-terminal processing of invariant
      chain (Ii) in late endosomes. CatS was active in all endocytic compartments.
      Surprisingly and in contrast with results from dendritic cells, inhibition of
      CatS activity by leucine-homophenylalanine-vinylsulfone-phenol prevented N
      terminal processing of Ii but did not alter the subcellular trafficking or
      surface delivery of class II complexes, as deferred from pulse-chase analysis in
      combination with subcellular fractionation and biotinylation of cell-surface
      protein. Thus, BLC contain distinct activity patterns of proteases in endocytic
      compartments and regulate the intracellular transport and surface-delivery of
      class II in a CatS-independent manner.

PMID- 14966191
TI  - Diesel exhaust particles increase LPS-stimulated COX-2 expression and PGE2
      production in human monocytes.
AB  - Little is known about health effects of ultrafine particles (UFP) found in
      ambient air, but much of their action may be on cells of the lung, including
      cells of the monocyte/macrophage lineage. We have analyzed the effects of diesel
      exhaust particles (DEP; SRM1650a) on human monocytes in vitro. DEP, on their own,
      had little effect on cyclooxygenase (COX)-2 gene expression in the Mono Mac 6
      cell line. However, when cells were preincubated with DEP for 1 h, then
      stimulation with the Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS)
      induced an up-to fourfold-higher production of COX-2 mRNA with an average twofold
      increase. This costimulatory effect of DEP led to enhanced production of COX-2
      protein and to increased release of prostaglandin E(2) (PGE(2)). The effect was
      specific in that tumor necrosis factor gene expression was not enhanced by DEP
      costimulation. Furthermore, costimulation with the TLR2 ligand Pam3Cys also led
      to enhanced COX-2 mRNA. DEP and LPS showed similar effects on COX-2 mRNA in
      primary blood mononuclear cells, in highly purified CD14-positive monocytes, and
      in monocyte-derived macrophages. Our data suggest that UFP such as DEP may exert
      anti-inflammatory effects mediated by enhanced PGE(2) production.

PMID- 14966192
TI  - Streptococcus pyogenes and Lactobacillus rhamnosus differentially induce
      maturation and production of Th1-type cytokines and chemokines in human monocyte
      derived dendritic cells.
AB  - Dendritic cells (DCs) are the most efficient antigen-presenting cells and thus,
      have a major role in regulating host immune responses. In the present study, we
      have analyzed the ability of Gram-positive, pathogenic Streptococcus pyogenes and
      nonpathogenic Lactobacillus rhamnosus to induce the maturation of human monocyte
      derived DCs. Stimulation of DCs with S. pyogenes resulted in strong expression of
      DC costimulatory molecules CD80, CD83, and CD86 accompanied with a T helper cell
      type 1 (Th1) cytokine and chemokine response. S. pyogenes also induced
      interleukin (IL)-2 and IL-12 production at mRNA and protein levels. In addition,
      IL-23 and IL-27 subunits p40, p19, p28, and EBI3 were induced at mRNA level. In
      contrast, L. rhamnosus-stimulated DCs showed only moderate expression of
      costimulatory molecules and produced low levels of cytokines and chemokines.
      Furthermore, no production of IL-2 or IL-12 family cytokines was detected.
      Bacteria-induced DC maturation and especially cytokine and chemokine production
      were reduced when bacteria were heat-inactivated. Our results show that human
      monocyte-derived DCs respond differently to different Gram-positive bacteria.
      Although pathogenic S. pyogenes induced a strong Th1-type response, stimulation
      with nonpathogenic L. rhamnosus resulted in development of semi-mature DCs
      characterized by moderate expression of costimulatory molecules and low cytokine
      production.

PMID- 14966193
TI  - Cross-regulation of CD86 by CD80 differentially regulates T helper responses from
      Mycobacterium tuberculosis secretory antigen-activated dendritic cell subsets.
AB  - We report that stimulation of Mycobacterium tuberculosis secretory antigen- and
      tumor necrosis factor alpha-matured BALB/c mouse bone marrow dendritic cells
      (BMDCs) with anti-CD80 monoclonal antibody up-regulated CD86 levels on the cell
      surface. Coculture of these BMDCs with naive, allogeneic T cells now down
      regulated T helper cell type 1 (Th1) responses and up-regulated suppressor
      responses. Similar results were obtained with splenic CD11c(+)/CD8a(-) DCs but
      not to the same extent with CD11c(+)/CD8a(+) DCs. Following coculture with T
      cells, only BMDCs and CD11c(+)/CD8a(-) DCs and not CD11c(+)/CD8a(+) DCs displayed
      increased levels of surface CD86, and further, coculturing these DCs with a fresh
      set of T cells attenuated Th1 responses and increased suppressor responses. Not
      only naive but even antigen-specific recall responses of the Th1-committed cells
      were modulated by DCs expressing up-regulated surface CD86. Further analyses
      showed that stimulation with anti-CD80 increased interleukin (IL)-10 and
      transforming growth factor-beta-1 levels with a concomitant reduction in IL-12p40
      and interferon-gamma levels from BMDCs and CD11c(+)/CD8a(-) DCs and to a lesser
      extent, from CD11c(+)/CD8a(+) DCs. These results suggest that cross-talk between
      costimulatory molecules differentially regulates their relative surface densities
      leading to modulation of Th responses initiated from some DC subsets, and Th1
      committed DCs such as CD11c(+)/CD8a(+) DCs may not allow for such modulation.
      Cognate antigen-presenting cell (APC):T cell interactions then impart a level of
      polarization on APCs mediated via cross-regulation of costimulatory molecules,
      which govern the nature of subsequent Th responses.

PMID- 14966194
TI  - TGF-beta: the perpetrator of immune suppression by regulatory T cells and
      suicidal T cells.
AB  - Innate and adaptive immunity function to eliminate foreign invaders and respond
      to injury while enabling coexistence with commensal microbes and tolerance
      against self and innocuous agents. Although most often effective in accomplishing
      these objectives, immunologic processes are not fail-safe and may underserve or
      be excessive in protecting the host. Checks and balances to maintain control of
      the immune system are in place and are becoming increasingly appreciated as
      targets for manipulating immunopathologic responses. One of the most recognized
      mediators of immune regulation is the cytokine transforming growth factor-beta
      (TGF-beta), a product of immune and nonimmune cells. Emerging data have unveiled
      a pivotal role for TGF-beta as a perpetrator of suppression by CD4(+)CD25(+)
      regulatory T (Treg) cells and in apoptotic sequelae. Through its
      immunosuppressive prowess, TGF-beta effectively orchestrates resolution of
      inflammation and control of autoaggressive immune reactions by managing T cell
      anergy, defining unique populations of Treg cells, regulating T cell death, and
      influencing the host response to infections.

PMID- 14966195
TI  - Annexin 1 and the biology of the neutrophil.
AB  - This overview will focus on one aspect of neutrophil biology, which is the
      selective activation of the annexin 1 system in relation to the process of cell
      extravasation. Besides the current view about the biochemistry of annexin 1 and
      annexin 1 receptor(s) up-regulation within the microenvironment of the adherent
      neutrophils, we will also comment on the final result achieved by activation of
      the system, which is inhibition of neutrophil recruitment. In view of the
      historical link between annexin 1 and glucocorticoids, the potential for the
      annexin 1 system in mediating at least some of the anti-inflammatory actions of
      these powerful drugs is also discussed.

PMID- 14966196
TI  - Cannabinoid receptor-mediated regulation of intracellular calcium by delta(9)
      tetrahydrocannabinol in resting T cells.
AB  - Cannabinoids exhibit broad immune modulating activity by targeting many cell
      types within the immune system, including T cells, which exhibit sensitivity, as
      evidenced by altered activation, proliferation, and cytokine expression. As a
      result of the critical role calcium plays in T cell function coupled with
      previous findings demonstrating disruption of the calcium-regulated transcription
      factor, nuclear factor of activated T cells, by cannabinoid treatment, the
      objective of the present investigation was to perform an initial characterization
      of the role of the cannabinoid receptors in the regulation of the intracellular
      calcium concentration ([Ca(2+)](i)) by delta(9)-tetrahydrocannabinol (delta(9)
      THC) in T lymphocytes. Here, we demonstrate that delta(9)-THC robustly elevates
      [Ca(2+)](i) in purified murine splenic T cells and in the human peripheral blood
      acute lymphoid leukemia (HPB-ALL) human T cell line but only minimally elevates
      [Ca(2+)](i) in Jurkat E6-1 (dysfunctional cannabinoid receptor 2-expressing)
      human T cells. Removal of extracellular calcium severely attenuated the delta(9)
      THC-mediated rise in [Ca(2+)](i) in murine splenic T cells and HPB-ALL cells.
      Pretreatment with cannabinoid receptor antagonists, SR144528 and/or SR141716A,
      led to an attenuation of delta(9)-THC-mediated elevation in [Ca(2+)](i) in
      splenic T cells and HPB-ALL cells but not in Jurkat E6-1 cells. Furthermore,
      pretreatment of HPB-ALL cells with SR144528 antagonized the small rise in
      [Ca(2+)](i) elicited by delta(9)-THC in the absence of extracellular calcium.
      These findings suggest that delta(9)-THC induces an influx of extracellular
      calcium in resting T cells in a cannabinoid receptor-dependent manner.

PMID- 14966197
TI  - Ghrelin is expressed in a novel endocrine cell type in developing rat islets and
      inhibits insulin secretion from INS-1 (832/13) cells.
AB  - Ghrelin is produced mainly by endocrine cells in the stomach and is an endogenous
      ligand for the growth hormone secretagogue receptor (GHS-R). It also influences
      feeding behavior, metabolic regulation, and energy balance. It affects islet
      hormone secretion, and expression of ghrelin and GHS-R in the pancreas has been
      reported. In human islets, ghrelin expression is highest pre- and neonatally. We
      examined ghrelin and GHS-R in rat islets during development with
      immunocytochemistry and in situ hybridization. We also studied the effect of
      ghrelin on insulin secretion from INS-1 (832/13) cells and the expression of GHS
      R in these cells. We found ghrelin expression in rat islet endocrine cells from
      mid-gestation to 1 month postnatally. Islet expression of GHS-R mRNA was detected
      from late fetal stages to adult. The onset of islet ghrelin expression preceded
      that of gastric ghrelin. Islet ghrelin cells constitute a separate and novel
      islet cell population throughout development. However, during a short perinatal
      period a minor subpopulation of the ghrelin cells co-expressed glucagon or
      pancreatic polypeptide. Markers for cell lineage, proliferation, and duct cells
      revealed that the ghrelin cells proliferate, originate from duct cells, and share
      lineage with glucagon cells. Ghrelin dose-dependently inhibited glucose
      stimulated insulin secretion from INS-1 (832/13) cells, and GHS-R was detected in
      the cells. We conclude that ghrelin is expressed in a novel developmentally
      regulated endocrine islet cell type in the rat pancreas and that ghrelin inhibits
      glucose-stimulated insulin secretion via a direct effect on the beta-cell.

PMID- 14966198
TI  - Immunohistochemical characterization of the orphan nuclear receptor ROR alpha in
      the mouse nervous system.
AB  - ROR alpha is an orphan nuclear receptor. A deletion mutation in the ROR alpha
      gene leads to severe cerebellar defects, known as the staggerer mutant mouse.
      Although previous in situ hybridization (ISH) studies have shown that ROR alpha
      is highly expressed in the cerebellum, especially in Purkinje cells, and in the
      thalamus, sufficient immunohistochemical (IHC) study has not yet been presented.
      I demonstrate here the IHC analysis of ROR alpha using a specific anti-ROR alpha
      antibody, in adult and developing mouse nervous system. ROR alpha
      immunoreactivity was observed in the Purkinje cell and molecular layers of the
      cerebellum. The co-localization of ROR alpha with calbindin D(28K) (CaBP) and
      parvalbumin indicates that ROR alpha-positive cells were Purkinje cells, stellate
      cells, and basket cells. In addition to the cerebellum, strong to medium ROR
      alpha immunoreactivity was found in the thalamus, cerebral cortex (mainly in the
      layer IV), dorsal cochlear nucleus (DCN), suprachiasmatic nucleus (SCN), superior
      colliculus, spinal trigeminal nucleus, and retina. The immunostaining was
      restricted in nuclei of neurons. Developmentally, ROR alpha immunoreactivity was
      observed in the cerebellum and thalamus from embryonal day 16 (E16). The
      distribution of ROR alpha immunoreactivity and ROR alpha mRNA hybridization
      signal was almost coincident. However, the intensity of hybridization signal was
      not always parallel to that of immunoreactivity.

PMID- 14966199
TI  - Bronchial branching correlates with specific glycosidase activity, extracellular
      glycosaminoglycan accumulation, TGF beta(2), and IL-1 localization during chick
      embryo lung development.
AB  - During organ differentiation, cell-extracellular matrix (ECM) interactions are
      required. The components of the ECM, such as glycosaminoglycans, fibronectin,
      laminin, and collagens, change in relation to cytokine and enzyme activity.
      Moreover, glycosaminoglycans (GAGs) are components of the ECM that play an
      important role in both cytokine regulation and cell activities. In this work we
      studied the accumulation of hyaluronic acid and chondroitin sulfate and heparan
      sulfate proteoglycans (PGs), beta-N-acetyl-D-glucosaminidase activity, the
      presence of transforming growth factor beta(2) (TGF beta(2)), and interleukin-1
      (IL-1), and the localization of fibronectin, laminin, and collagen I and IV
      during the early stages of chick embryo lung development. We also determined the
      levels of hyaluronic acid, chondroitin sulfate, dermatan sulfate, and heparan
      sulfate GAGs and the activity of beta-N-acetyl-D-glucosaminidase with biochemical
      methods. Our data show that beta-N-acetyl-D-glucosaminidase activity increases in
      each cell, especially in the epithelial growth front at the emergence of each
      bronchial bud, where hyaluronic acid and IL-1 are located in the surrounding
      mesenchymal areas. Chondroitin sulfate and heparan sulfate PGs, fibronectin,
      laminin, and collagen I and IV are evident in the area near the basal membrane
      along the sides where the forming structures are stabilized. Biochemical data
      show that beta-N-acetyl-D-glucosaminidase activity increases in cells during lung
      development and is related to GAG decrease and to modifications of the
      nonsulfated/sulfated GAG ratio. These modifications could change cytokine
      activity and play an important role in bronchial branching development.

PMID- 14966200
TI  - NT agonist regulates expression of nuclear high-affinity neurotensin receptors.
AB  - Neurotensin (NT) exerts multiple functions in the central nervous system and
      peripheral tissues. Its actions are mainly mediated by a high-affinity G-protein
      coupled receptor, the NT-1 receptor. In this study we demonstrated a nuclear NT
      binding site in different cellular models. We first noted that a large percentage
      of NT-1 receptor cell body immunoreactivity was located in the nuclear soma and
      nuclear envelope of rat substantia nigra, a brain area rich in NT-containing axon
      terminals. The NT-1 receptor was also visualized in purified nuclei from CHO
      cells stably transfected with NT-1 receptor coupled to the enhanced green
      fluorescence protein by immunocytochemistry. We observed that both the nuclear
      envelope and the nuclear soma were labeled, and the labeling intensity
      significantly increased after NT agonist treatment. These results suggested that
      NT-1 receptors, present in both the nuclear soma and the nuclear envelope, can be
      modulated by the ligand. Lastly, [(125)I]-NT binding experiments performed on
      isolated nuclei from a human lung cancer cell line endogenously expressing NT-1
      receptor and NT, LNM35, revealed the existence of nuclear Gpp(NHp)-sensitive
      binding sites. These binding sites markedly decreased when cells were chronically
      treated with an NT-1 receptor antagonist, SR 48692. Taken together, these data
      suggest that the agonist regulates the expression of nuclear NT-1 receptors.

PMID- 14966201
TI  - Immunofluorescence and confocal laser scanning microscopy of chronic
      myeloproliferative disorders on archival formaldehyde-fixed bone marrow.
AB  - Spatial analysis of the histoarchitecture and photographic documentation at high
      resolution are the principal advantages of confocal laser scanning microscopy
      (CLSM) over conventional fluorescence microscopy (CFM) if combined with
      appropriate software. Restrictions for the use of CFM and CLSM, on the other
      hand, include nonspecific background fluorescence, fading of photolabile
      fluorochromes, and both tissue-specific and fixation-induced autofluorescence.
      Most of those shortcomings can now be avoided. Autofluorescence, the most
      limiting factor of high-resolution CLSM, was recently controlled also for
      paraffin sections of archival formaldehyde-fixed tissues. This allowed the
      present study on cytoskeletal fibers and extracellular matrix proteins in both
      neoplastic cells of myeloproliferative disorders and in medullary stromal cells
      using CLSM under proper autofluorescence control. By multiple fluorescence
      labeling, we found that the intracellular smooth muscle alpha-actin (SMA) fibers
      and the two extracellular adhesive matrix proteins tenascin and fibronectin vary
      in their presence in stromal and/or myeloid cells according to the degree of bone
      marrow fibrosis in chronic myeloproliferative disorders (CMPDs). CLSM offers
      further insight in our attempts to understand a complex interplay between the two
      cellular compartments.

PMID- 14966202
TI  - Expression of estrogen receptors in human corpus cavernosum and male urethra.
AB  - Estrogen, largely produced in testis and adrenal gland, may play important roles
      in male reproduction. Most of the effects of estrogens are mediated by binding of
      estrogen to one or both of the two estrogen receptor (ER) subtypes alpha and
      beta. Recently, they have been described in testis, prostate, and efferent ducts,
      mostly in rodents. The goal of this study was to prove the evidence of ERs in
      human corpus cavernosum and male urethra, exploring the protein expression of
      these receptors by immunohistochemistry. Corpus cavernosum and corpus spongiosum
      smooth muscle was immunoreactive for the androgen receptor (AR), ER alpha, and
      strongly for ER beta. Endothelial cells were negative for AR, sporadically
      positive for ER alpha, and positive for ER beta. Urethral epithelium showed
      strong nuclear expression of AR, predominantly in the basal cell layer, and
      nuclear expression of ER alpha in the intermediate cells. ER beta was highly
      expressed in almost all urethral nuclei and, much more weakly, in cytoplasm.
      Progesterone receptor (PGR) was negative in all cases and all tissues. These
      results represent the first report that ER alpha and particularly ER beta are
      regularly expressed in human penile tissue.

PMID- 14966203
TI  - Immunocytochemical localization of histatins in human salivary glands.
AB  - Histatins are a family of salivary proteins with bactericidal and fungicidal
      activities that contribute to the innate defense of the oral cavity. Histatins
      are present in the serous granules of the parotid and submandibular glands. The
      important role of histatins in saliva, and the limited information on their
      cellular and subcellular distribution, prompted us to further define the
      localization of histatins in the major salivary glands. Immunogold-silver
      staining of 1- micro m sections of plastic-embedded tissue with anti-histatin
      antibody revealed histatin immunoreactivity in the serous acinar cells of the
      parotid and submandibular glands, the serous demilune cells of the submandibular
      and sublingual glands, and in occasional intercalated duct cells. No reactivity
      was seen in mucous cells or in striated or excretory duct cells. Electron
      microscopic observations of thin sections labeled with anti-histatin and gold
      labeled secondary antibodies revealed immunoreactivity associated with the rough
      endoplasmic reticulum and Golgi complex and in secretory granules of serous
      acinar and demilune cells. The granules of parotid acinar cells exhibited
      relatively uniform labeling of their content, whereas the granules of serous
      cells in the submandibular and sublingual glands showed variable labeling of the
      dense and light regions of their content. A few intercalated duct cells adjacent
      to the acinar cells also exhibited labeled granules. These results suggest that
      the serous cells of the major glands are the main source of histatins in human
      saliva. They are also consistent with several previous studies demonstrating the
      variable distribution of different proteins within the granule content.

PMID- 14966204
TI  - Developmental expression of Pop1/Bves.
AB  - Initial studies have suggested that Pop1/Bves protein is exclusively expressed in
      the smooth muscle walls of the coronary vessels, implying its possible importance
      in coronary diseases. However, the mRNA and activity of this gene are detected in
      both skeletal and cardiac muscles, not coronary smooth muscle, and Pop1/Bves
      knockout mice have defects in skeletal muscle regeneration. Here we used specific
      monoclonal antibodies (MAbs) raised against chicken Pop1/Bves and demonstrated
      the presence of this protein in cardiomyocytes through development and its
      apparent absence in coronary vessels. Immunostaining of cardiomyocytes cultured
      in vitro confirmed the membrane localization of this protein in cells that
      participate in cell adhesion, with significant intracellular staining seen in
      isolated cells. In skeletal muscle, Pop1 protein becomes detectable at embryonic
      day (E) 7, coincident with the differentiation of morphologically distinct muscle
      masses from the limb muscle blastema, but the protein is not found at high levels
      in the cell membrane of myotubes until E11, coincident with the formation of
      secondary myotubes from satellite cells. These data support the hypothesis that
      Pop1/Bves is a cell adhesion molecule present in skeletal and cardiac muscle.

PMID- 14966205
TI  - Innervation of pulmonary neuroendocrine cells and neuroepithelial bodies in
      developing rabbit lung.
AB  - We investigated the development of innervation of the pulmonary neuroendocrine
      cell (PNEC) system composed of single cells and organoid cell clusters,
      neuroepithelial bodies (NEB) in rabbit fetal and neonatal lungs. To visualize the
      nerve fibers and their contacts with PNECs/NEBs, we used confocal microscopy and
      multilabel immunohistochemistry (IHC) with pan-neural marker, synaptic vesicle
      protein 2 (SV2), and serotonin (5-HT) as markers for PNECs/NEBs, and smooth
      muscle actin or cytokeratin to identify airway landmarks. The numbers and
      distribution of PNEC/NEB at different stages of lung development (E16, 18, 21,
      26, and P2) and the density of innervation were quantified. First PNECs
      immunoreactive for 5-HT were identified in primitive airway epithelium at E18 as
      single cells or as small cell clusters with or without early nerve contacts. At
      E21 a significant increase in the number of PNECs with formation of early
      innervated NEB corpuscules was observed. The overall numbers of PNECs/NEBs and
      the density of mucosal, submucosal, and intercorpuscular innervation increased
      with progressing gestation and peaked postnatally (P2). At term, the majority of
      NEBs and single PNECs within airway mucosa possessed neural contacts. Such an
      extensive and complex innervation of the PNEC system indicates a multifunctional
      role in developing lung and during neonatal adaptation.

PMID- 14966206
TI  - Expression and distribution of somatostatin receptor subtypes in the pancreatic
      islets of mice and rats.
AB  - Somatostatin acts on specific membrane receptors (sst(1-5)) to inhibit exocrine
      and endocrine functions. The aim was to investigate the distribution of sst(1-5)
      in pancreatic islet cells in normal mice and rats. Pancreatic samples from five
      adult C57BL/6 mice and Sprague-Dawley rats were stained with antibodies against
      sst(1-5) and insulin, glucagon, somatostatin, or pancreatic polypeptide (PP). A
      quantitative analysis of the co-localization was performed. All ssts were
      expressed in the pancreatic islets and co-localized on islet cells to various
      extents. A majority of the beta-cells expressed sst(1-2) and sst(5) in mouse
      islets, while < or =50% in the rat expressed sst(1-5). The expression of sst(1-5)
      on alpha-cells did not differ much among species, with sst(2) and sst(5) being
      highly expressed. About 70% of the delta-cells expressed sst(1-4) in the rat
      pancreas, whereas 50% of the islet cells expressed sst(1-5) in the mouse.
      Furthermore, 60% of the PP-cells expressed sst(1-5) in the mouse, while the rat
      islets had lower values. Co-expression with the four major islet hormones varies
      among species and sst subtypes. These similarities and differences are
      interesting and need further evaluation to elucidate their physiological role in
      islets.

PMID- 14966207
TI  - Localization and enhanced mRNA expression of the orphan chemokine receptor L-CCR
      in the lung in a murine model of ovalbumin-induced airway inflammation.
AB  - Various CC chemokine receptors are expressed on effector cells in allergic
      inflammation and their distinct expression pattern may dictate, to a large
      extent, the migration of inflammatory cells to sites of airway inflammation. The
      lipopolysaccharide (LPS)-inducible CC chemokine receptor (L-CCR) is an orphan
      chemokine receptor that has previously been identified in the murine macrophage
      cell line RAW 264.7 and in murine brain glial cells. In this study we
      investigated the induction and localization of L-CCR mRNA expression in mouse
      lung after ovalbumin (OVA)-induced airway inflammation. Both RT-PCR experiments
      and in situ hybridization (ISH) experiments in whole lung sections revealed a
      rapid upregulation of L-CCR mRNA expression as early as 1 hr and 3 hr after OVA
      challenge. Expression was found predominantly in MAC3(+) macrophages and in
      bronchial epithelium, as shown by ISH and immunohistochemistry (IHC). We
      demonstrated that L-CCR mRNA expression is strongly upregulated in mouse lung
      after OVA challenge and is localized in macrophages and bronchial epithelium.
      Regarding the likely role of L-CCR as a chemokine receptor with the putative
      ligand monocyte chemotactic protein-1 (MCP-1, CCL2), this receptor may have an
      important function in the early phase of airway inflammation.

PMID- 14966208
TI  - Fluorescence-based staining for tartrate-resistant acidic phosphatase (TRAP) in
      osteoclasts combined with other fluorescent dyes and protocols.
AB  - Osteoclasts are the only bone-resorbing cells. In addition to other specific
      properties, osteoclasts are characterized by their expression of tartrate
      resistant acidic phosphatase (TRAP), which is usually detected using a
      histochemical method for light microscopy. Using ELF97 phosphatase substrate,
      this study describes a new fluorescence-based method for TRAP detection. The
      fluorescence-based ELF97 TRAP stain not only results in a better resolution of
      the TRAP-positive granules, because confocal microscopy can be applied for image
      acquisition and analysis, but it reveals additional and more specific information
      about osteoclasts because it can be combined with other fluorescence-based
      methods.

PMID- 14966209
TI  - Calcium-activated chloride channel-2 in human epithelia.
AB  - Calcium-activated chloride channels (CLCAs) are a family of multifunctional
      proteins that are widely distributed in tissues. To investigate the distribution
      of human CLCA-2 (hCLCA2) in human epithelia at the light and electron microscopic
      levels, we raised a primary antibody against a synthetic polypeptide sequence
      from natural hCLCA2. Corneal, skin, vaginal, esophageal, and laryngeal epithelia
      were immunopositive for hCLCA2 at the cytosolic aspect of the basal cells
      adjacent to the basement membrane. Epithelia of stomach and small intestine
      showed no hCLCA2 immunoreactivity. This study reports the cellular distribution
      of hCLCA2 in human epithelia and suggests its possible involvement in epithelial
      stratification and cell-substrate adhesion.

PMID- 14966210
TI  - Immunohistochemical analysis of advanced human breast carcinomas reveals
      downregulation of protein kinase C alpha.
AB  - Forty-six advanced-stage human breast carcinoma specimens were evaluated by
      immunohistochemistry for PKC alpha expression and compared with 25 samples of
      normal adjacent breast tissue. For normal tissue, the median staining of ductal
      epithelia was of moderate intensity. No staining was observed for 67% of tumor
      specimens, and only 4% showed intensities greater than the median observed in
      normal tissue. Faint to moderate PKC alpha staining was observed in the stroma,
      inflammatory cells, and fibroblasts of tumors but was absent in normal tissue.
      These findings demonstrate that downregulation of PKC alpha protein occurs in
      epithelial cells of advanced breast tumors (p<0.001).

PMID- 14966211
TI  - Solid-state 13C-NMR spectroscopy shows that the xyloglucans in the primary cell
      walls of mung bean (Vigna radiata L.) occur in different domains: a new model for
      xyloglucan-cellulose interactions in the cell wall.
AB  - Xyloglucans (XG) with different mobilities were identified in the primary cell
      walls of mung beans (Vigna radiata L.) by solid-state 13C-NMR spectroscopy. To
      improve the signal:noise ratios compared with unlabelled controls, Glc labelled
      at either C-1 or C-4 with 13C-isotope was incorporated into the cell-wall
      polysaccharides of mung bean hypocotyls. Using cell walls from seedlings labelled
      with d-[1-13C]glucose and, by exploiting the differences in rotating-frame and
      spin-spin proton relaxation, a small signal was detected which was assigned to
      Xyl of XGs with rigid glucan backbones. After labelling seedlings with d-[4
      13C]glucose and using a novel combination of spin-echo spectroscopy with proton
      spin relaxation-editing, signals were detected that had 13C-spin relaxations and
      chemical shifts which were assigned to partly-rigid XGs surrounded by mobile non
      cellulosic polysaccharides. Although quantification of these two mobility types
      of XG was difficult, the results indicated that the partly-rigid XGs were
      predominant in the cell walls. The results lend support to the postulated new
      cell-wall models in which only a small proportion of the total surface area of
      the cellulose microfibrils has XG adsorbed on to it. In these new models, the
      partly-rigid XGs form cross-links between adjacent cellulose microfibrils and/or
      between cellulose microfibrils and other non-cellulosic polysaccharides, such as
      pectic polysaccharides.

PMID- 14966212
TI  - MGOUN3, an Arabidopsis gene with TetratricoPeptide-Repeat-related motifs,
      regulates meristem cellular organization.
AB  - In order to understand the functioning of apical meristems in Arabidopsis more
      clearly, a new mutant, mgoun3 (mgo3), affected in the structural organization and
      the functional regulation of both shoot and root meristems has been isolated.
      mgo3 plants display perturbations in leaf morphogenesis, in the spatial and the
      temporal formation of primordia, and frequent fasciation of the inflorescence
      stem. Cellular analysis showed that both cellular organization and cell identity
      patterning are impaired in the mutant meristems. The MGO3 gene has been isolated
      by positional cloning. The protein deduced from the cDNA sequence contains
      TetratricoPeptide Repeats (TPR) and Leucine-Rich Repeats (LRR), two motifs that
      are thought to act in protein-protein interactions. This gene appears to be
      unique in the Arabidopsis genome. Although the MGO3 protein presents TPR as in
      the Arabidopsis proteins HOBBIT and SPINDLY, the MGO3 motifs are more similar to
      those present in LGN-related proteins, which are regulators for some of the
      asymmetric cell divisions in animal development. These features suggest a key
      role for MGO3 in meristematic cell divisions and would be of interest for the
      comparison between plant and animal development.

PMID- 14966213
TI  - The effect of reduced glutathione on morphology and gene expression of white
      spruce (Picea glauca) somatic embryos.
AB  - Inclusions of reduced glutathione (GSH) in the maturation medium increased the
      conversion frequency of white spruce somatic embryos without the need of a
      partial drying treatment (PDT). This beneficial effect was the result of major
      alterations in morphology and gene expression during the maturation period.
      Compared with control embryos, GSH-treated embryos showed a differential
      accumulation of storage products, i.e. preferential deposition of starch, the
      reduced formation of protein bodies, and increased vacuolation of cells. These
      morphological changes correlated with extensive alterations of gene expression
      occurring throughout the maturation period. The transcript profiles of stage
      specific embryos matured with or without GSH were analysed using a DNA microarray
      containing 2 178 cDNAs from loblolly pine (Pinus taeda). The efficiency of
      heterologous hybridization between spruce and pine species on microarrays has
      previously been documented. The results indicate that several genes involved in a
      variety of signal regulatory pathways were differentially expressed in developing
      GSH- treated embryos. The transcript levels of many genes involved in
      carbohydrate metabolism and protein synthesis were altered by the presence of GSH
      and denoted differences in physiology between treatments. Extensive changes in
      the expression of genes participating in hormone synthesis, nucleotide
      metabolism, and meristem formation were also observed and related to the post
      embryonic performance of the embryos.

PMID- 14966214
TI  - Changes in gene expression during meristem activation processes in Solanum
      tuberosum with a focus on the regulation of an auxin response factor gene.
AB  - A suppression subtractive hybridization approach (SSH) was used to generate a
      cDNA library enriched in clones representing genes that are up-regulated in the
      potato tuber apical bud on dormancy release. The sequences of cDNAs representing
      385 different genes were determined. This study focuses on the characterization
      of one of these cDNAs. On the basis of sequence similarity, the cDNA was
      identified as encoding a member of the auxin response factor family (ARF6). The
      expression pattern of potato ARF6 was determined by in situ hybridization. In
      apical tuber buds in the early stages of sprouting, relatively high levels of
      ARF6-specific transcripts were detected, especially in the peripheral zones of
      the tunica and corpus of the apical meristems. Expression was also detected in
      procambial and early vascular tissues, both subtending the meristem and in
      adjacent leaf primordia. By contrast, in dormant buds no expression of ARF6 could
      be detected. The expression pattern was also determined during the tuberization
      process; steady-state expression levels decreased c. 10-fold in the apical region
      as tuberization proceeded. In non-growing buds, exhibiting correlative
      inhibition, ARF6-specific transcript levels were relatively low, but rapidly
      increased when apical dominance was removed by excision of the apical bud. The
      effects of gibberellin and auxin on axillary bud growth and ARF6 expression are
      described.

PMID- 14966215
TI  - The effect of Botrytis cinerea infection on the antioxidant profile of
      mitochondria from tomato leaves.
AB  - Infection of tomato leaves with the necrotrophic fungus Botrytis cinerea resulted
      in substantial changes in enzymatic and non-enzymatic components of the ascorbate
      glutathione cycle as well as in superoxide dismutase (SOD), glutathione
      peroxidase (GSH-Px), glutathione transferase (GST), and l-galactono-gamma-lactone
      dehydrogenase (GLDH) activities. In the initial phase of the 5 d experiment CuZn
      SOD was the most rapidly induced isoform (up to 209% of control), whereas later
      on its activity increase was not concomitant with the constant total SOD
      enhancement. Starting from the second day B. cinerea infection diminished the
      mitochondrial antioxidant capacity by decreasing activities of ascorbate
      peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate
      reductase (DHAR) as well as declining ascorbate and glutathione contents. This
      was accompanied by dehydroascorbate (DHA) and oxidized glutathione (GSSG)
      accumulation that resulted in ascorbate and glutathione redox ratios decreases.
      The strongest redox ratio decline of 29% for ascorbate and of 34% for glutathione
      was found on the 3rd and 2nd days, respectively. Glutathione reductase (GR)
      induction (185% of control 2 d after inoculation) was insufficient to overcome
      the decreased antioxidant potential of glutathione. Changes in the ascorbate pool
      size were closely related to the activity of l-galactono-gamma-lactone
      dehydrogenase (GLDH). The activities of two glutathione-dependent enzymes: GSH-Px
      and GST were increased from day 1 to day 4. These results demonstrated that in B.
      cinerea-tomato interaction mitochondria could be one of the main targets for
      infection-induced oxidative stress.

PMID- 14966216
TI  - Self assembly of epicuticular waxes on living plant surfaces imaged by atomic
      force microscopy (AFM).
AB  - The cuticle of terrestrial vascular plants and some bryophytes is covered with a
      complex mixture of lipids, usually called epicuticular waxes. Self-assembly
      processes of wax molecules lead to crystalline three-dimensional micro- and
      nanostructures that emerge from an underlying wax film. This paper presents the
      first AFM study on wax regeneration on the surfaces of living plants and the very
      early stages of wax crystal formation at the molecular level. Wax formation was
      analysed on the leaves of Euphorbia lathyris, Galanthus nivalis, and Ipheion
      uniflorum. Immediately after wax removal, regeneration of a wax film began,
      consisting of individual layers of, typically, 3-5 nm thickness. Subsequently,
      several different stages of crystal growth could be distinguished, and different
      patterns of wax regeneration as well as considerable variation in regeneration
      speed were found.

PMID- 14966217
TI  - Characterization of Arabidopsis ZIM, a member of a novel plant-specific GATA
      factor gene family.
AB  - The Arabidopsis gene ZIM encodes a putative transcription factor containing a
      novel GATA-type zinc-finger domain with a longer spacer between its two sets of
      conserved cysteine residues (C-X2-C-X20-C-X2-C). In Arabidopsis, ZIM and
      homologous proteins, ZML1 and ZML2, were identified as GATA factors containing
      the C-X2-C-X20-C-X2-C motif, a CCT domain, and an uncharacterized conserved
      domain. Proteins that possess this domain structure were found exclusively in
      plants, indicating that they belong to a novel family of plant-specific GATA-type
      transcription factors. When ZIM was overexpressed using a CaMV 35S promoter in
      Arabidopsis, hypocotyls and petioles were elongated. The elongation phenotype was
      observed under all wavelengths of light tested and even in the presence of
      biosynthetic inhibitors of either brassinosteroid or gibberellin. In ZIM
      overexpressing plants, XTH33 which is predicted to function in cell wall
      modification was detected as an up-regulated gene by microarray analysis, and
      this could account for the elongation phenotype. Genes in ZIM-overexpressing
      plants were identified that were up-regulated in a tissue-specific manner, which
      suggests that transcriptional regulation by ZIM and its consequent effects are
      spatially controlled.

PMID- 14966218
TI  - A glycolate dehydrogenase in the mitochondria of Arabidopsis thaliana.
AB  - The fixation of molecular O2 by the oxygenase activity of Rubisco leads to the
      formation of phosphoglycolate in the chloroplast that is further metabolized in
      the process of photorespiration. The initial step of this pathway is the
      oxidation of glycolate to glyoxylate. Whereas in higher plants this reaction
      takes place in peroxisomes and is dependent on oxygen as a co-factor, most algae
      oxidize glycolate in the mitochondria using organic co-factors. The
      identification and characterization of a novel glycolate dehydrogenase in
      Arabidopsis thaliana is reported here. The enzyme is dependent on organic co
      factors and resembles algal glycolate dehydrogenases in its enzymatic properties.
      Mutants of E. coli incapable of glycolate oxidation can be complemented by
      overexpression of the Arabidopsis open reading frame. The corresponding RNA
      accumulates preferentially in illuminated leaves, but was also found in other
      tissues investigated. A fusion of the N-terminal part of the Arabidopsis
      glycolate dehydrogenase to red fluorescent protein accumulates in mitochondria
      when overexpressed in the homologous system. Based on these results it is
      proposed that the basic photorespiratory system of algae is conserved in higher
      plants.

PMID- 14966219
TI  - Mechanisms underlying the amelioration of O3-induced damage by elevated
      atmospheric concentrations of CO2.
AB  - There is growing evidence that rising atmospheric CO2 concentrations will reduce
      or prevent reductions in the growth and productivity of C3 crops attributable to
      ozone (O3) pollution. In this study, the role of pollutant exclusion in mediating
      this response was investigated through growth chamber-based investigations on
      leaves 4 and 7 of spring wheat (Triticum aestivum cv. Hanno). In the core
      experiments, plants were raised at two atmospheric CO2 concentrations (ambient
      [350 micro l l(-1)] or elevated CO2 [700 micro l l(-1)] under two O3 regimes
      (charcoal/Purafil-filtered air [<5 nl l(-1) O3] or ozone-enriched air [75 nl l(
      1) 7 h d(-1)]). A subsequent experiment used an additional O3 treatment where the
      goal was to achieve equivalent daily O3 uptake over the life-span of leaves 4 and
      7 under ambient and CO2-enriched conditions, through daily adjustment of
      exposures based on measured shifts in stomatal conductance. Plant growth and net
      CO2 assimilation were stimulated by CO2-enrichment and reduced by exposure to O3.
      However, the impacts of O3 decreased with plant age (i.e. leaf 7 was more
      resistant to O3 injury than leaf 4); a finding consistent with ontogenic shifts
      in the tolerance of plant tissue and/or acclimation to O3-induced oxidative
      stress. In the combined treatment, elevated CO2 protected against the adverse
      effects of O3 and reduced cumulative O3 uptake (calculated from measurements of
      stomatal conductance) by c. 10% and 35% over the life-span of leaves 4 and 7,
      respectively. Analysis of the relationship between O3 uptake and the decline in
      the maximum in vivo rate of Rubisco carboxylation (Vcmax) revealed the protection
      afforded by CO2-enrichment to be due, to a large extent, to the exclusion of the
      pollutant from the leaf interior (as a consequence of the decline in stomatal
      conductance triggered by CO2-enrichment), but there was evidence (especially from
      flux-response relationships constructed for leaf 4) that CO2-enrichment resulted
      in additional effects that alleviated the impacts of ozone-induced oxidative
      stress on photosynthesis.

PMID- 14966220
TI  - Repressed ethylene production in the gynoecium of long-lasting flowers of the
      carnation 'White Candle': role of the gynoecium in carnation flower senescence.
AB  - Ethylene production and expression of ethylene biosynthetic genes was
      investigated in senescing flowers of carnation (Dianthus caryophyllus L.)
      cultivars 'White Candle (WC)' and 'Light Pink Barbara (LPB)', with long and short
      vase-lives, respectively. Ethylene production from the gynoecium and petals of
      senescing 'WC' flowers was below the limit of detection, in agreement with the
      repressed ethylene production from the whole flowers. However, exogenous ethylene
      treatment caused the accumulation of transcripts for DC-ACS1 and DC-ACO1 genes in
      both the gynoecium and petals, resulting in ethylene production from the flowers.
      Moreover, application of ABA or IAA, which are known to exhibit their action
      through the induction of ethylene synthesis in the gynoecium, to 'WC' flowers
      from their cut stem-end induced ethylene production and wilting in the flowers.
      These findings suggested that, in 'WC' flowers the mechanism of ethylene
      biosynthesis, i.e. the induction of expression of genes for ethylene biosynthesis
      and the action of resulting enzymes, was not defective, but that its function was
      repressed during natural senescence. Transcripts of DC-ACO1, DC-ACS3, and DC-ACS1
      were present in the gynoecium of senescing 'LPB' flowers. In the gynoecium of
      senescing 'WC' flowers, however, the DC-ACO1 transcript was present, but the DC
      ACS1 transcript was absent and the DC-ACS3 transcript was detected only in a
      small amount; the latter two were associated with the low rate of ethylene
      production in the gynoecium of 'WC' flowers. These findings indicated that the
      repressed ethylene production in 'WC' flowers during natural senescence is caused
      by the repressed ethylene production in the gynoecium, giving further support for
      the role of the gynoecium in regulating petal senescence in carnation flowers.

PMID- 14966221
TI  - Carbon and water relations for developing fruits of Opuntia ficus-indica (L.)
      Miller, including effects of drought and gibberellic acid.
AB  - Growth, gas exchange rates, and carbohydrate content were studied for developing
      fruits of the cultivated cactus Opuntia ficus-indica (L.) Miller, including
      effects of drought and exogenous gibberellic acid (GA3). Fruit development
      required 110 d from the time of bud differentiation to ripening at 80 d after
      anthesis, when the fruit mass averaged 67 g. Stomatal conductance and net CO2
      uptake rates for fruits were higher during the night; they were maximal at 7 d
      before anthesis and decreased as development progressed. Fruits undergoing
      drought, imposed by detaching terminal stems bearing fruits, were 50% smaller
      than the control at 80 d after anthesis and did not ripen. Fruits injected with 2
      ml of 500 ppm GA3 were 30% smaller than the control at 80 d after anthesis; they
      contained a large proportion of aborted seeds that produced a weak sink signal
      for dry mass accumulation. Gas exchange was higher at 21 d after anthesis for
      fruits treated with GA3. Total soluble sugars represented 40% of the fruit's dry
      mass until 45 d after anthesis, when the sugar content rapidly increased,
      reaching 90% at 73 d after anthesis. Such an increase was not observed for fruits
      treated with GA3, and the sugar content for fruits undergoing drought remained
      low throughout development. Starch content increased for developing fruits of O.
      ficus-indica until 14 d after anthesis and, except for the fruits undergoing
      drought, decreased thereafter. Fruit development for O. ficus-indica is
      apparently regulated by water availability as well as hormonal signals
      originating both within and outside the fruit.

PMID- 14966222
TI  - Mechanical stabilization of desiccated vegetative tissues of the resurrection
      grass Eragrostis nindensis: does a TIP 3;1 and/or compartmentalization of
      subcellular components and metabolites play a role?
AB  - During dehydration, numerous metabolites accumulate in vegetative desiccation
      tolerant tissues. This is thought to be important in mechanically stabilizing the
      cells and membranes in the desiccated state. Non-aqueous fractionation of
      desiccated leaf tissues of the resurrection grass Eragrostis nindensis (Ficalho
      and Hiern) provided an insight into the subcellular localization of the
      metabolites (because of the assumptions necessary in the calculations the data
      must be treated with some caution). During dehydration of the desiccant-tolerant
      leaves, abundant small vacuoles are formed in the bundle sheath cells, while cell
      wall folding occurs in the thin-walled mesophyll and epidermal cells, leading to
      a considerable reduction in the cross-sectional area of these cells. During
      dehydration, proline, protein, and sucrose accumulate in similar proportions in
      the small vacuoles in the bundle sheath cells. In the mesophyll cells high
      amounts of sucrose accumulate in the cytoplasm, with proline and proteins being
      present in both the cytoplasm and the large central vacuole. In addition to the
      replacement of water by compatible solutes, high permeability of membranes to
      water may be critical to reduce the mechanical strain associated with the influx
      of water on rehydration. The immunolocalization of a possible TIP 3;1 to the
      small vacuoles in the bundle sheath cells may be important in both increased
      water permeability as well as in the mobilization of solutes from the small
      vacuoles on rehydration. This is the first report of a possible TIP 3;1 in
      vegetative tissues (previously only reported in orthodox seeds).

PMID- 14966223
TI  - Housing standards: a glossary of housing and health.
AB  - This glossary has been designed to provide definitions that take account of
      different disciplinary and policy traditions and to consider the aspects of
      housing that provide scope for possible concerted research and action.

PMID- 14966225
TI  - Health impact assessment as an agent of policy change: improving the health
      impacts of the mayor of London's draft transport strategy.
AB  - OBJECTIVE: To increase the positive and mitigate the negative health impacts of
      the mayor's draft transport strategy for London. DESIGN: A rapid prospective
      health impact assessment (HIA) of the penultimate draft of the strategy, using a
      review commissioned by the regional director of public health; an appraisal of
      congestion charging; and a participatory workshop. Two audits of changes were
      performed to assess the impact on policy of the HIA process. SETTING: Regional
      government policy development. INTERVENTION: Recommendations from the rapid HIA
      were fed back into the drafting process. MAIN OUTCOME MEASURE: Changes (a)
      between the penultimate draft and the draft for public consultation and (b)
      between that and the final mayoral strategy. RESULTS: The draft transport
      strategy published for consultation differed in a number of respects from the
      previous version. Almost all the recommendations from the HIA were incorporated
      into the final strategy. Significant changes included promoting sustainable
      travel plans for workplaces and schools; giving priority to infrastructure and
      services that benefit London's deprived communities; increased emphasis on
      promoting walking and cycling and reducing reliance on private cars; and a
      commitment to track the health impacts of the final strategy and its
      implementation. Specific additions included re-allocating road space. CONCLUSION:
      HIA was successful in influencing the transport strategy for London, resulting in
      several improvements from a health viewpoint. HIA is an effective method both for
      bringing about significant change in policy proposals and in increasing policy
      makers' understanding of determinants of health and hence in changing attitudes
      of policy makers.

PMID- 14966226
TI  - The politics of preventable deaths: local spending, income inequality, and
      premature mortality in US cities.
AB  - OBJECTIVE: To examine the association between (1) local political party, (2)
      urban policies, measured by spending on local programmes, and (3) income
      inequality with premature mortality in large US cities. DESIGN: Cross sectional
      ecological study. OUTCOME MEASURES: All cause death rates and death rates
      attributable to preventable or immediate causes for people under age 75.
      PREDICTOR MEASURES: Income inequality, city spending, and social factors.
      SETTING: All central cities in the US with population equal to or greater than
      100 000. RESULTS: Income inequality is the most significant social variable
      associated with preventable or immediate death rates, and the relation is very
      strong: a unit increase in the Gini coefficient is associated with 37% higher
      death rates. Spending on police is associated with 23% higher preventable death
      rates compared with 14% lower death rates in cities with high spending on roads.
      CONCLUSIONS: Cities with high income inequality and poverty are so far unable to
      reduce their mortality through local expenditures on public goods, regardless of
      the mayoral party. Longitudinal data are necessary to determine if city spending
      on social programmes reduces mortality over time.

PMID- 14966227
TI  - How did general practitioners protect themselves, their family, and staff during
      the SARS epidemic in Hong Kong?
AB  - CONTEXT: Severe acute respiratory syndrome (SARS) is a newly emerging infectious
      disease and how the frontline community doctors respond to it is not known.
      OBJECTIVES: To explore the impact of SARS on general practitioners (GPs) in Hong
      Kong. DESIGN: A cross sectional survey. SETTING: Community based primary care
      clinics. PARTICIPANTS: 183 family medicine tutors affiliated with a local
      university. Postal survey sent to all tutors with a 74.8% response rate. MAIN
      OUTCOME MEASURES: Change of clinical behaviour and practices during the epidemic;
      anxiety level of primary care doctors. RESULTS: All agreed SARS had changed their
      clinical practices. Significant anxiety was found in family doctors. Three
      quarters of respondents recalled requesting more investigations while a quarter
      believed they had over-prescribed antibiotics. GPs who were exposed to SARS or
      who had worked in high infection districts were less likely to quarantine
      themselves (10.8% versus 33.3%; p<0.01; 6.5% versus 27.5%; p<0.01 respectively).
      Exposure to SARS, the infection rates in their working district, and anxiety
      levels had significant impact on the level of protection or prescribing
      behaviour. CONCLUSION: The clinical practice of GPs changed significantly as a
      result of SARS. Yet, those did not quarantine themselves suggesting other factors
      may have some part to play. As failure to apply isolation precautions to
      suspected cases of SARS was one major reason for its spread, a contingency plan
      from the government to support family doctors is of utmost importance. Interface
      between private and public sectors are needed in Hong Kong to prepare for any
      future epidemics.

PMID- 14966229
TI  - Modelling potential responses to severe acute respiratory syndrome in Japan: the
      role of initial attack size, precaution, and quarantine.
AB  - BACKGROUND: There has been an outbreak of the severe acute respiratory syndrome
      (SARS) worldwide. With the use of detailed epidemiological data from other
      countries, this article describes the possible reason for the SARS epidemic not
      appearing in Japan, and simulates the impact of different control strategies that
      can break the transmission cycle of SARS associated coronavirus. METHOD:
      Mathematical modelling is used for predicting the epidemiological outcome and
      simultaneously for evaluating the effect of interventions on SARS. The study
      estimates the initial attack size that would result in failed invasion. Three
      different interventions have been incorporated into the public health response
      policies; precautionary public health measures, isolation of infected people, and
      quarantine of exposed humans. RESULTS: The maximum number of humans newly
      infected could be roughly estimated on the basis of the initial attack size,
      using simple formulas. It is seen that the introduction of only a few cases into
      certain communities would not lead easily to an epidemic. The possible
      trajectories of SARS epidemic depend on the levels of public health interventions
      as quarantine and precautionary public health measures greatly affected the
      transmissibility of the disease. It is shown that there exist threshold levels of
      interventions at which the SARS epidemic settles down. CONCLUSION: Initial attack
      size is one of the determinants of whether SARS can successfully invade the
      community or not. Two of the most effective policy procedures to prevent new
      infections would be to apply stringent precautionary measures and to impose
      quicker and more effective quarantine of the exposed populace.

PMID- 14966230
TI  - Linking perceptions of neighbourhood to health in Hamilton, Canada.
AB  - STUDY OBJECTIVE: To investigate the association between perceptions of
      neighbourhood physical and social characteristics and three health outcomes (self
      assessed health status, chronic conditions, and emotional distress). DESIGN:
      Cross sectional survey data analysed in small neighbourhoods. SETTING: Hamilton,
      Ontario, Canada, a medium sized industrial city, located at the western end of
      Lake Ontario (population at the time of the study about 380 000). PARTICIPANTS:
      Random sample of 1504 adults aged 18 years and older residing in four contrasting
      neighbourhoods. MAIN RESULTS: Significant differences across the four
      neighbourhoods are apparent in self assessed health status and emotional
      distress, but not in chronic conditions. Neighbourhoods with lower SES reported
      poorer health and more emotional distress. Perceptions of the physical
      environment dominated social concerns in all neighbourhoods. For all three health
      outcomes, individual risk factors followed expectations, with measures of
      poverty, age, and lifestyle all significantly associated with poor health
      outcomes. Physical environmental problems were positively and significantly
      associated with poor physical and emotional health. Specifically, people
      reporting they dislike aspects of their neighbourhood's physical environment are
      1.5 times more likely to report chronic health conditions (OR 1.56, 95% CI 1.19
      to 2.05), while those reporting physical likes with their neighbourhood are less
      likely to report fair/poor health (OR 0.50, 95% CI 0.28 to 0.90) or emotional
      distress (OR 0.45, 95% CI 0.26 to 0.80). CONCLUSIONS: These results demonstrate
      the importance of neighbourhood perceptions as a determinant of health, as well
      as conventional factors such as low income, lifestyle, and age. The dominance of
      physical environmental concerns may have arisen from the industrial nature of
      Hamilton, but this result merits further investigation.

PMID- 14966232
TI  - The role of individual and contextual socioeconomic circumstances on mortality:
      analysis of time variations in a city of north west Italy.
AB  - STUDY OBJECTIVE: To evaluate the independent and mutual effects of neighbourhood
      deprivation and of individual socioeconomic conditions on mortality and to assess
      the trends over the past 30 years and the residual neighbourhood heterogeneity.
      DESIGN: General and cause specific mortality was analysed as a function of time
      period, highest educational level achieved, housing conditions, and neighbourhood
      deprivation, using multilevel Poisson models stratified by gender and age class.
      SETTING: The study was conducted in Turin, a city in north west Italy with nearly
      one million inhabitants and consisting of 23 neighbourhoods. PARTICIPANTS: The
      study population included three cohorts of persons aged 15 years or older,
      recorded in the censuses of 1971, 1981, and 1991 and followed up for 10 years
      after each census. MAIN RESULTS: Individual and contextual socioeconomic
      conditions showed an independent and significant impact on mortality, both among
      men and women, with significantly higher risks for coronary heart and respiratory
      diseases among people, aged less than 65 years, residing in deprived
      neighbourhoods (9% and 15% excess for coronary heart diseases, 20% and 24% for
      respiratory diseases, respectively for men and women living in deprived
      neighbourhoods compared with rich). The decreasing time trend in general
      mortality was less pronounced among men with lower education and poorer housing
      conditions, compared with their more advantaged counterparts; the same was found
      in less educated women aged less than 65 years. CONCLUSIONS: These results and
      further developments in the evaluation of impact and mechanisms of other
      contextual effects can provide information for both health and non-health
      oriented urban policies.

PMID- 14966233
TI  - A multilevel analysis of socioeconomic (small area) differences in household food
      purchasing behaviour.
AB  - STUDY OBJECTIVE: To examine the association between area and individual level
      socioeconomic status (SES) and food purchasing behaviour. DESIGN: The sample
      comprised 1000 households and 50 small areas. Data were collected by face to face
      interview (66.4% response rate). SES was measured using a composite area index of
      disadvantage (mean 1026.8, SD = 95.2) and household income. Purchasing behaviour
      was scored as continuous indices ranging from 0 to 100 for three food types:
      fruits (mean 50.5, SD = 17.8), vegetables (61.8, 15.2), and grocery items (51.4,
      17.6), with higher scores indicating purchasing patterns more consistent with
      dietary guideline recommendations. SETTING: Brisbane, Australia, 2000.
      PARTICIPANTS: Persons responsible for their household's food purchasing. MAIN
      RESULTS: Controlling for age, gender, and household income, a two standard
      deviation increase on the area SES measure was associated with a 2.01 unit
      increase on the fruit purchasing index (95% CI -0.49 to 4.50). The corresponding
      associations for vegetables and grocery foods were 0.60 (-1.36 to 2.56) and 0.94
      (-1.35 to 3.23). Before controlling for household income, significant area level
      differences were found for each food, suggesting that clustering of household
      income within areas (a composition effect) accounted for the purchasing
      variability between them. CONCLUSIONS: Living in a socioeconomically advantaged
      area was associated with a tendency to purchase healthier food, however, the
      association was small in magnitude and the 95% CI for area SES included the null.
      Although urban areas in Brisbane are differentiated on the basis of their
      socioeconomic characteristics, it seems unlikely that where you live shapes your
      procurement of food over and above your personal characteristics.

PMID- 14966234
TI  - Housing and health in Germany.
AB  - STUDY OBJECTIVES: To examine the association between housing tenure and self
      rated health, controlling for socioeconomic measures and testing the mediating
      effects of physical features of the home, pollution in the local environment, and
      relationships with neighbours. DESIGN: Cross sectional panel study with people
      nested within households. Analyses were performed using multilevel methods.
      SETTING: Population based sample in Germany. PARTICIPANTS: People aged 16 or
      older were interviewed in the 1999 wave of the socio-economic panel study (n = 14
      055) and nested within households (n = 7381). MAIN RESULTS: 44.0% of the
      population lived in homes that they owned. In bivariate analyses, women, people
      who live in apartment buildings, reside near cities, live in crowded homes, have
      homes in need of renovation, report higher pollution, and have distant contact
      with neighbours are more likely to live in rented homes. In multilevel analyses,
      renting a home was found to be associated with poor self rated health (OR 1.48,
      95% CI 1.31 to 1.68). This relation persisted after controlling for education and
      income and was partially mediated by the need for household renovation, the
      perception of air and noise pollution in the local area, and distant relationship
      with neighbours, all of which were significantly associated with self rated
      health. CONCLUSIONS: This study provides evidence that home ownership is
      significantly associated with self rated health in Germany, and this relation may
      be, in part, mediated by physical and social features of home and neighbourhood.

PMID- 14966236
TI  - Neighbourhoods and homicide mortality: an analysis of race/ethnic differences.
AB  - OBJECTIVE: To examine whether measures of neighbourhood economic deprivation,
      social disorganisation, and acculturation explain homicide mortality
      differentials between Mexican Americans, non-Hispanic black Americans, and non
      Hispanic white Americans, net of individual factors. DESIGN: Prospective study,
      National Health Interview Survey (1986-1994) linked to subsequent mortality in
      the National Death Index (1986-1997). SETTING: United States of America.
      PARTICIPANTS: A nationally representative sample of non-institutionalised Mexican
      Americans, non-Hispanic black Americans, and non-Hispanic white Americans, aged
      18-50 at the point of interview. ANALYSIS: Cox proportional hazard models
      estimate the risk of death associated with various neighbourhood and individual
      factors. MAIN RESULTS: Both individual and neighbourhood risk factors partially
      account for race/ethnic disparities in homicide. Homicide mortality risks are
      between 20% and 50% higher for residents of areas that have economic inequality
      of 0.50 or greater based on the coefficient of variation, or where 4% or more of
      the residents are Mexican American, 10% or more of the residents are non-Hispanic
      black, or 20% or more of the households are headed by single parents (p< or =
      0.05). But residents of areas where 10% or more of their neighbours are foreign
      born have 35% lower mortality risks than people living in areas with fewer
      foreign born people (p< or =0.05). These differences persist even after
      controlling for individual level risk factors. CONCLUSIONS: The findings support
      economic deprivation, social disorganisation, and acculturation theories, and
      suggest that both neighbourhood and individual risk factors affect race/ethnic
      differences in homicide mortality. Public health policies must focus on both
      individual and neighbourhood factors to reduce homicide risks in vulnerable
      populations.

PMID- 14966238
TI  - "Unequal opportunity": neighbourhood disadvantage and the chance to buy illegal
      drugs.
AB  - STUDY OBJECTIVES: This study investigates whether subgroups of people living in
      disadvantaged neighbourhoods may be more likely to come into contact with drug
      dealers as compared with persons living in more advantaged areas, with due
      attention to male-female and race-ethnicity differences. DESIGN: Standardised
      survey data collected using stratified, multistage area probability sampling.
      SETTING: United States of America, 1998. PARTICIPANTS: Nationally representative
      sample of household residents age 12 or older (n = 25 500). MAIN RESULTS:
      Evidence supports an inference that women are less likely to be approached by
      someone selling illegal drugs. The study found no more than modest and generally
      null racial and ethnicity differences, even for residents living within socially
      disadvantaged neighbourhoods, where chances to buy illegal drugs are found to be
      more common. CONCLUSIONS: Limitations of survey data always merit attention, but
      this study evidence lends support to the inference that physical and social
      characteristics of a neighbourhood can set the stage for opportunities to become
      involved with drugs.

PMID- 14966239
TI  - Contribution of drinking patterns to differences in rates of alcohol related
      problems between three urban populations.
AB  - OBJECTIVES: To examine, on empirical data, whether drinking patterns, in addition
      to overall alcohol consumption, contribute to differences in rates of alcohol
      related problems between populations. DESIGN: Cross sectional survey. SETTINGS:
      One Russian, one Polish, and one Czech city. PARTICIPANTS: 1118 men and 1125
      women randomly selected from population registers. MAIN OUTCOME MEASURES: Problem
      drinking; negative social consequences of drinking; alcohol consumption and
      drinking pattern. RESULTS: Rates of problem drinking and of negative consequences
      of drinking were much higher in Russian men (35% and 18%, respectively) than in
      Czechs (19% and 10%) or Poles (14% and 8%). This contrasts with substantially
      lower mean annual intake of alcohol reported by Russian men (4.6 litres) than by
      Czech men (8.5 litres), and with low mean drinking frequency in Russia (67
      drinking sessions per year, compared with 179 sessions among Czech men). However,
      Russians consumed the highest dose of alcohol per drinking session (means 71 g in
      Russians, 46 g in Czechs, and 45 g in Poles), and had the highest prevalence of
      binge drinking. In women, the levels of alcohol related problems and of drinking
      were low in all countries. In ecological and individual level analyses,
      indicators of binge drinking explained a substantial part of differences in rates
      of problem drinking and negative consequences of drinking between the three
      countries. CONCLUSIONS: These empirical data confirm high levels of alcohol
      related problems in Russia despite low volume of drinking. The binge drinking
      pattern partly explains this paradoxical finding. Overall alcohol consumption
      does not suffice as an estimate of alcohol related problems at the population
      level.

PMID- 14966240
TI  - Evaluation of methodologies for small area life expectancy estimation.
AB  - STUDY OBJECTIVE: To evaluate methods for calculating life expectancy in small
      areas, for example, English electoral wards. DESIGN: The Monte Carlo method was
      used to simulate the distribution of life expectancy (and its standard error)
      estimates for 10 alternative life table models. The models were combinations of
      Chiang or Silcocks methodology, 5 or 10 year age intervals, and a final age
      interval of 85+, 90+, or 95+. SETTING: A hypothetical small area experiencing the
      population age structure and age specific mortality rates of English men 1998
      2000. PARTICIPANTS: Routine mortality and population statistics for England. MAIN
      RESULTS: Silcocks and Chiang based models gave similar estimates of life
      expectancy and its standard error. For all models, life expectancy was
      increasingly overestimated as the simulated population size decreased. The degree
      of overestimation depended largely on the final age interval chosen. Life
      expectancy estimates of small populations are normally distributed. The standard
      error estimates are normally distributed for large populations but become
      increasingly skewed as the population size decreases. Substitution methods to
      compensate for the effect of zero death counts on the standard error estimate did
      not improve the estimate. CONCLUSIONS: It is recommended that a population years
      at risk of 5000 is a reasonable point above which life expectancy calculations
      can be performed with reasonable confidence. Implications are discussed. Within
      the UK, the Chiang methodology and a five year life table to 85+ is recommended,
      with no adjustments to age specific death counts of zero.

PMID- 14966241
TI  - The Index of Multiple Deprivation 2000 and accessibility effects on health.
AB  - STUDY OBJECTIVE: To investigate whether the Index of Multiple Deprivation 2000
      (IMD) is more strongly related to inequalities in health in rural areas than
      traditional deprivation indices. To explore the contribution of the IMD domain
      "geographical access to services" to understanding rural health variations.
      DESIGN: A geographically based cross sectional study. SETTING: Nine counties in
      the south west region of England. PARTICIPANTS: All those aged below 65 who
      reported a limiting long term illness in the 1991 census, and all those who died
      during 1991-96, aged less than 65 years. MAIN RESULTS: The IMD is comparable with
      the Townsend score in its overall correlation with premature mortality (r(2) =
      0.44 v 0.53) and morbidity (r(2) = 0.79 v 0.76). Correlation between the Townsend
      score and population health is weak in rural areas but the IMD maintains a strong
      correlation with rates of morbidity (r(2) = 0.70). The "geographical access to
      services" domain of the IMD is not strongly correlated with rates of morbidity in
      rural areas (r(2) = 0.04), and in urban areas displays a negative correlation
      (r(2) = -0.47). CONCLUSIONS: The IMD has a strong relation with health in both
      rural and urban areas. This is likely to be the result of the inclusion of data
      in the IMD on the numbers of people claiming benefits related to ill health and
      disability. The domain "geographical access to services" is not associated with
      health in rural areas, although it displays some association in urban areas. This
      domain is potentially important but, as yet, inadequately specified in the IMD
      for the purposes of health research.

PMID- 14966242
TI  - Bullying, workers' health, and labour instability.

PMID- 14966244
TI  - Carpe diem. Retooling the publish or perish model into the share and survive
      model.

PMID- 14966245
TI  - Profiling of Arabidopsis secondary metabolites by capillary liquid chromatography
      coupled to electrospray ionization quadrupole time-of-flight mass spectrometry.
AB  - Large-scale metabolic profiling is expected to develop into an integral part of
      functional genomics and systems biology. The metabolome of a cell or an organism
      is chemically highly complex. Therefore, comprehensive biochemical phenotyping
      requires a multitude of analytical techniques. Here, we describe a profiling
      approach that combines separation by capillary liquid chromatography with the
      high resolution, high sensitivity, and high mass accuracy of quadrupole time-of
      flight mass spectrometry. About 2000 different mass signals can be detected in
      extracts of Arabidopsis roots and leaves. Many of these originate from
      Arabidopsis secondary metabolites. Detection based on retention times and exact
      masses is robust and reproducible. The dynamic range is sufficient for the
      quantification of metabolites. Assessment of the reproducibility of the analysis
      showed that biological variability exceeds technical variability. Tools were
      optimized or established for the automatic data deconvolution and data
      processing. Subtle differences between samples can be detected as tested with the
      chalcone synthase deficient tt4 mutant. The accuracy of time-of-flight mass
      analysis allows to calculate elemental compositions and to tentatively identify
      metabolites. In-source fragmentation and tandem mass spectrometry can be used to
      gain structural information. This approach has the potential to significantly
      contribute to establishing the metabolome of Arabidopsis and other model systems.
      The principles of separation and mass analysis of this technique, together with
      its sensitivity and resolving power, greatly expand the range of metabolic
      profiling.

PMID- 14966246
TI  - A proteomic analysis of maize chloroplast biogenesis.
AB  - Proteomics studies to explore global patterns of protein expression in plant and
      green algal systems have proliferated within the past few years. Although most of
      these studies have involved mapping of the proteomes of various organs, tissues,
      cells, or organelles, comparative proteomics experiments have also led to the
      identification of proteins that change in abundance in various developmental or
      physiological contexts. Despite the growing use of proteomics in plant studies,
      questions of reproducibility have not generally been addressed, nor have
      quantitative methods been widely used, for example, to identify protein
      expression classes. In this report, we use the de-etiolation ("greening") of
      maize (Zea mays) chloroplasts as a model system to explore these questions, and
      we outline a reproducible protocol to identify changes in the plastid proteome
      that occur during the greening process using techniques of two-dimensional gel
      electrophoresis and mass spectrometry. We also evaluate hierarchical and
      nonhierarchical statistical methods to analyze the patterns of expression of 526
      "high-quality," unique spots on the two-dimensional gels. We conclude that
      Adaptive Resonance Theory 2-a nonhierarchical, neural clustering technique that
      has not been previously applied to gene expression data-is a powerful technique
      for discriminating protein expression classes during greening. Our experiments
      provide a foundation for the use of proteomics in the design of experiments to
      address fundamental questions in plant physiology and molecular biology.

PMID- 14966247
TI  - Evolutionary dynamics of the DNA-binding domains in putative R2R3-MYB genes
      identified from rice subspecies indica and japonica genomes.
AB  - The molecular evolution of the R2R3-MYB gene family is of great interest because
      it is one of the most important transcription factor gene families in the plant
      kingdom. Comparative analyses of a gene family may reveal important adaptive
      changes at the protein level and thereby provide insights that relate structure
      to function. We have performed a range of comparative and bioinformatics analyses
      on R2R3-MYB genes identified from the rice (Oryza sativa subsp. japonica and
      indica) and Arabidopsis genome sequences. The study provides an initial framework
      to investigate how different evolutionary lineages in a gene family evolve new
      functions. Our results reveal a remarkable excess of non-synonymous
      substitutions, an indication of adaptive selection on protein structure that
      occurred during the evolution of both helix1 and helix2 of rice R2R3-MYB DNA
      binding domains. These flexible alpha-helix regions associated with high
      frequencies of excess non-synonymous substitutions may play critical roles in the
      characteristic packing of R2R3-MYB DNA-binding domains and thereby modify the
      protein-DNA interaction process resulting in the recognition of novel DNA-binding
      sites. Furthermore, a co-evolutionary pattern is found between the second alpha
      helix of the R2 domain and the second alpha-helix of the R3 domain by examining
      all the possible alpha-helix pairings in both the R2 and R3 domains. This points
      to the functional importance of pairing interactions between related secondary
      structures.

PMID- 14966248
TI  - Tissue- and age-dependent differences in the complexation of cadmium and zinc in
      the cadmium/zinc hyperaccumulator Thlaspi caerulescens (Ganges ecotype) revealed
      by x-ray absorption spectroscopy.
AB  - Extended x-ray absorption fine structure measurements were performed on frozen
      hydrated samples of the cadmium (Cd)/zinc (Zn) hyperaccumulator Thlaspi
      caerulescens (Ganges ecotype) after 6 months of Zn(2+) treatment with and without
      addition of Cd(2+). Ligands depended on the metal and the function and age of the
      plant tissue. In mature and senescent leaves, oxygen ligands dominated. This
      result combined with earlier knowledge about metal compartmentation indicates
      that the plants prefer to detoxify hyperaccumulated metals by pumping them into
      vacuoles rather than to synthesize metal specific ligands. In young and mature
      tissues (leaves, petioles, and stems), a higher percentage of Cd was bound by
      sulfur (S) ligands (e.g. phytochelatins) than in senescent tissues. This may
      indicate that young tissues require strong ligands for metal detoxification in
      addition to the detoxification by sequestration in the epidermal vacuoles.
      Alternatively, it may reflect the known smaller proportion of epidermal metal
      sequestration in younger tissues, combined with a constant and high proportion of
      S ligands in the mesophyll. In stems, a higher proportion of Cd was coordinated
      by S ligands and of Zn by histidine, compared with leaves of the same age. This
      may suggest that metals are transported as stable complexes or that the vacuolar
      oxygen coordination of the metals is, like in leaves, mainly found in the
      epidermis. The epidermis constitutes a larger percentage of the total volume in
      leaves than in stems and petioles. Zn-S interaction was never observed,
      confirming earlier results that S ligands are not involved in Zn resistance of
      hyperaccumulator plants.

PMID- 14966250
TI  - The elusive field of systems biology.

PMID- 14966249
TI  - NopL, an effector protein of Rhizobium sp. NGR234, thwarts activation of plant
      defense reactions.
AB  - Bacterial effector proteins delivered into eukaryotic cells via bacterial type
      III secretion systems are important virulence factors in plant-pathogen
      interactions. Type III secretion systems have been found in Rhizobium species
      that form symbiotic, nitrogen-fixing associations with legumes. One such
      bacterium, Rhizobium sp. NGR234, secretes a number of type III effectors,
      including nodulation outer protein L (NopL, formerly y4xL). Here, we show that
      expression of nopL in tobacco (Nicotiana tabacum) prevents full induction of
      pathogenesis-related (PR) defense proteins. Transgenic tobacco plants that
      express nopL and were infected with potato virus Y (necrotic strain 605)
      exhibited only very low levels of chitinase (class I) and beta-1,3-glucanase
      (classes I and III) proteins. Northern-blot analysis indicated that expression of
      nopL in plant cells suppresses transcription of PR genes. Treatment with ethylene
      counteracted the effect of NopL on chitinase (class I). Transgenic Lotus
      japonicus plants that expressed nopL exhibited delayed development and low
      chitinase levels. In vitro experiments showed that NopL is a substrate for plant
      protein kinases. Together, these data suggest that NopL, when delivered into the
      plant cell, modulates the activity of signal transduction pathways that culminate
      in activation of PR proteins.

PMID- 14966251
TI  - Insights into the physiological role of WT1 from studies of genetically modified
      mice.
AB  - The identification of WT1 gene mutations in children with WAGR and Denys-Drash
      syndromes pointed toward a role for WT1 in genitourinary system development.
      Biochemical analysis of the different WT1 protein isoforms showed that WT1 is a
      transcription factor and also has the ability to bind RNA. Analysis of WT1
      complexes identified several target genes and protein partners capable of
      interacting with WT1. Some of these studies placed WT1, its downstream targets,
      and protein partners in a transcriptional regulatory network that controls
      urogenital system development. We review herein studies on WT1 knockout and
      transgenic models that have been instrumental in defining a physiological role
      for WT1 in normal and abnormal urogenital development.

PMID- 14966252
TI  - Temporal patterns of gene expression in murine cutaneous burn wound healing.
AB  - The global changes in gene expression in injured murine skin were characterized
      following a second-degree scald burn. Dorsal skin was harvested from uninjured
      and from burned mice at 2 h and at 3 and 14 days following immersion in 65
      degrees C water for 45 s. Gene expression was surveyed using an Affymetrix U74Av2
      GeneChip, and patterns of gene expression were analyzed using hierarchical
      clustering and supervised analysis. Burn injury produced significant alterations
      in the expression of a number of genes, with the greatest changes seen 3 and 14
      days after the scald burn. Using a supervised analysis with a false discovery
      rate of 1% or 5%, differences in the expression of 192 or 1,116 genes,
      respectively, discriminated among the unburned skin and the three time points
      after the burn injury. Gene expression was primarily a transient and time
      dependent upregulation. The expression of only 24 of the 192 discriminating genes
      was downregulated after the burn injury. No gene exhibited a sustained increase
      in expression over the entire 14 days following the burn injury. Gene ontologies
      revealed an integrated upregulation of inflammatory and protease genes at acute
      time intervals, and a diminution of cytoskeletal and muscle contractile genes at
      3 or 14 days after the injury. Following a second-degree scald burn, global
      patterns of gene expression in the burn wound change dramatically over several
      weeks in a time-dependent manner, and these changes can be categorized based on
      the biological relevance of the genes.

PMID- 14966253
TI  - Rhabdomyolysis associated with concomitant use of simvastatin and clarithromycin.

PMID- 14966254
TI  - Oral antivirals for the acute treatment of recurrent herpes labialis.
AB  - OBJECTIVE: To evaluate the use and benefit of oral antivirals in the acute
      treatment of episodic, recurrent herpes labialis. DATA SOURCES: A literature
      search was performed in MEDLINE (1966-August 2003) using acyclovir, famciclovir,
      valacyclovir, cold sores, herpes labialis, and HSV-1 as search terms. DATA
      SYNTHESIS: We reviewed 5 placebo-controlled and 2 comparative studies evaluating
      oral antivirals for acute treatment of recurrent herpes labialis. No studies
      directly compared different antivirals. Studies discussing the efficacy of
      antivirals for chronic suppression of herpes simplex virus-1 infection were not
      included. CONCLUSIONS: Treatment with oral antivirals decreases the duration of
      lesion episodes and pain by approximately one day; however, the antivirals do not
      abort lesions from developing. Clinical implications of these results appear
      relatively modest.

PMID- 14966255
TI  - Transient ischemic attack reported with paroxetine use.
AB  - OBJECTIVE: To report the occurrence of a transient ischemic attack (TIA)
      temporally related to the initiation of paroxetine. CASE SUMMARY: A 57-year-old
      white man with a history of intermittent atrial fibrillation and
      hypercholesterolemia developed slurred speech and a facial droop 3 days after
      starting paroxetine. He was diagnosed with a TIA, hospitalized, and given
      anticoagulation treatment. The presenting symptoms resolved, but recurred when
      paroxetine was restarted 2 days later. DISCUSSION: Platelets secrete serotonin,
      which mediates vasoconstriction through stimulation of 5-HT2a receptors. This is
      counterbalanced by the release of the vasodilator nitric oxide upon serotonin
      stimulation of endothelial 5-HT1 receptors. In conditions such as
      atherosclerosis, the damage to the endothelium leads to a greater
      vasoconstrictive response. Paroxetine has been reported to weakly inhibit
      norepinephrine reuptake and nitric oxide production in addition to increasing
      serotonergic activity, potentially compounding the vasoconstrictive response. An
      objective causality assessment revealed that the TIA was probably an adverse
      event resulting from use of paroxetine. CONCLUSIONS: Use of paroxetine and other
      selective serotonin-reuptake inhibitors may result in changes of the vasculature
      and subsequent ischemic events in predisposed patients.

PMID- 14966256
TI  - Pulmonary and hepatic toxicity due to nitrofurantoin and fluconazole treatment.
AB  - OBJECTIVE: To reemphasize potential risks associated with chronic nitrofurantoin
      use and to report a case of combined pulmonary and hepatic toxicity precipitated
      from acute use of fluconazole concomitantly with chronic nitrofurantoin. CASE
      SUMMARY: A 73-year-old white man taking nitrofurantoin 50 mg/day for 5 years
      developed combined hepatic and pulmonary toxicity after taking fluconazole
      acutely for onychomycosis. Two months after starting fluconazole, the patient's
      hepatic enzymes showed elevation 5 times the upper limits of normal. In addition,
      the patient reported fatigue, dyspnea on exertion, pleuritic pain, burning
      trachea pain, and a cough. Chest X-rays showed bilateral pulmonary disease
      consistent with nitrofurantoin toxicity. Both drugs were determined to be the
      cause of the patient's pulmonary and hepatic toxicity, so they were discontinued.
      Pulmonary function tests measured after discontinuation were abnormal and also
      consistent with nitrofurantoin toxicity. The patient's hepatic and pulmonary
      toxicity resolved upon discontinuation of both drugs and use of inhaled
      corticosteroids. DISCUSSION: Changes in hepatic enzyme measurement, pulmonary
      function measurements, and chest X-rays indicate that our patient developed
      hepatic and pulmonary toxicity due to his drug therapy. An objective causality
      assessment revealed that these adverse events were probably due to fluconazole
      given with nitrofurantoin. Either drug may have caused the hepatic toxicity.
      However, it is possible that pharmacokinetic changes induced by an interaction
      with fluconazole precipitated the nitrofurantoin-induced pulmonary toxicity.
      CONCLUSIONS: Our patient developed pulmonary and hepatic toxicity after starting
      fluconazole in combination with chronic nitrofurantoin. A potential drug
      interaction of unknown mechanism may have been the cause of the toxicities.

PMID- 14966257
TI  - Detoxification from high-dose zolpidem using diazepam.
AB  - OBJECTIVE: To report a rare case of physical and psychological addiction to an
      excessive dose of zolpidem and subsequent completed detoxification using
      diazepam. CASE SUMMARY: A 46-year-old white man with a history of polysubstance
      abuse received a prescription for zolpidem 2 years prior to his hospital
      detoxification. During that time, he gradually escalated the total dosage to an
      amount of 400 mg/day in divided doses. Upon hospitalization, he was detoxified
      using a standard benzodiazepine 7-day diazepam tapering regimen. DISCUSSION:
      Zolpidem is a nonbenzodiazepine medication approved for the short-term treatment
      of insomnia. Its mechanism is a selective benzodiazepine type 1 receptor agonist.
      The selectivity of the drug for the type 1 receptor may not be absolute and is
      inversely dose dependent. Compared with the benzodiazepines, zolpidem addiction
      is rare. However, at higher than recommended doses for extended periods of time,
      its addictive potential may be similar to that of the benzodiazepines.
      CONCLUSIONS: Given the similarities in receptor binding and pharmacologic
      activities of zolpidem and the benzodiazepines, we chose to use a standard
      benzodiazepine detoxification protocol to treat zolpidem withdrawal. Confirmation
      of this has been evidenced by successful zolpidem detoxification using a standard
      7-day benzodiazepine/diazepam taper regimen.

PMID- 14966258
TI  - Use of epoetin alfa in critically ill patients.
AB  - OBJECTIVE: To discuss the controversies regarding the use of epoetin alfa (EPO)
      for reducing red blood cell (RBC) transfusions in critically ill patients with
      anemia. DATA SOURCES: A MEDLINE search (1966-July 2003) was conducted using the
      search terms anemia; critical illness; erythropoietin; epoetin alfa; and
      erythropoietin, recombinant. References of selected articles were reviewed for
      studies that may have been missed by the computerized search. STUDY SELECTION AND
      DATA EXTRACTION: Studies pertaining to the use of EPO for anemia of critical
      illness with an emphasis on data obtained from controlled trials. DATA SYNTHESIS:
      Anemia is a common complication in patients admitted to the intensive care unit
      (ICU). Two prospective, randomized studies have demonstrated decreased
      transfusion requirements associated with EPO administration in medical/surgical
      patients who were in the ICU for at least 3 days and had hematocrit
      concentrations <38%. No differences were found in length of stay or mortality. A
      multicenter trial found that a restrictive strategy of RBC transfusion
      (hemoglobin goal 7-9 g/dL) was associated with in-hospital mortality lower than
      that with a more liberal approach, which calls into question the 38% hematocrit
      goal in the EPO trials. Furthermore, preliminary results from an economic
      analysis of EPO use in the ICU setting have demonstrated that EPO is not cost
      effective. CONCLUSIONS: Given the controversies surrounding EPO administration in
      critically ill patients, institutions are encouraged to develop EPO guidelines to
      help ensure the most appropriate use of this expensive product. Additional
      studies regarding patients most likely to benefit from EPO therapy, the most
      effective dosing regimen, and use of adjunctive therapies are needed.

PMID- 14966259
TI  - Factors that influence prescribing decisions.
AB  - BACKGROUND: Strategies to control the quality and cost of medication use are
      largely dependent on the ability to alter selection of medications. Previous
      models of prescribing behavior have focused on physicians. In the hospital
      setting, clinical pharmacists and formulary committee members are also key
      players in drug therapy decision-making. Differences between physicians,
      formulary committee members, and clinical pharmacists have not been compared.
      Knowledge of these differences could have importance in predicting the
      effectiveness of strategies designed to influence drug use in this setting.
      OBJECTIVE: To describe and compare the opinions of physicians, clinical
      pharmacists, and formulary committee members with respect to key factors that
      influence medication prescribing in community hospitals. METHODS: Physicians,
      clinical pharmacists, and formulary committee members were solicited to
      participate. A trained interviewer administered a standardized questionnaire
      designed to elicit opinions of participants regarding the importance of factors
      thought to influence drug prescribing. Responses were described using descriptive
      statistics, and differences between the groups were determined by post hoc
      analysis. RESULTS: A total of 150 individuals participated in the study. Safety,
      effectiveness, formulary status, and restrictions on prescribing were considered
      highly influential by all participants. Physicians rated the availability of drug
      samples and personal experience higher (more influential on prescribing) than
      clinical pharmacists and formulary committee members. Clinical pharmacists and
      formulary committee members rated the influence of recommendations by clinical
      pharmacists, prescribing guidelines, and cost or cost comparisons higher than
      physicians. Factors that were drug-related or that involved policy-related
      programs tended to be more influential than indirect factors. CONCLUSIONS: Those
      who seek to implement programs to alter medication use should recognize and
      employ factors that are most influential in the decision-making process. Further,
      it may be important to consider differences that exist between key participants
      in the medication use process.

PMID- 14966260
TI  - Quetiapine-associated acute dystonia.

PMID- 14966261
TI  - Reliability of gene expression ratios for cDNA microarrays in multiconditional
      experiments with a reference design.
AB  - In a typical gene expression profiling experiment with multiple conditions, a
      common reference sample is used for co-hybridization with the samples to yield
      expression ratios. Differential expression for any other sample pair can then be
      calculated by assembling the ratios from their hybridizations with the reference.
      In this study we test the validity of this approach. Differential expression of a
      sample pair (i, j) was obtained in two ways: directly, by hybridizations of
      sample i versus j, and indirectly, by multiplying the expression ratios for
      hybridizations of sample i versus pool and pool versus sample j. We performed
      gene expression profiling using amphibian embryos (Xenopus laevis). Every sample
      combination of four different stages and a pool was profiled. Direct and indirect
      values were compared and used as the quality criterion for the data. Based on
      this criterion, 82% of all ratios were found to be sufficiently accurate. To
      increase the reliability of the signals, several widely used filtering techniques
      were tested. Filtering by differences of repeated hybridizations was found to be
      the optimal filter. Finally, we compared microarray-based gene expression
      profiles with the corresponding expression patterns obtained by whole-mount in
      situ hybridizations, resulting in a 90% correspondence.

PMID- 14966262
TI  - Doxycycline regulation in a single retroviral vector by an autoregulatory loop
      facilitates controlled gene expression in liver cells.
AB  - The tetracycline system has limitations in liver cells, such as toxic effects and
      low controllability. We generated different retroviral vectors for controlled
      gene expression in liver cells, in which the regulatory elements were arranged in
      different patterns. Only the organization of the tetracycline system in an
      autoregulatory loop in the sense orientation results in high retroviral titres
      and in tight regulation of gene expression in highly differentiated hepatoma
      cells. Because of the toxicity of the transactivator tTA, it was impossible to
      establish doxycycline-dependent stable HepG2 cell lines. To avoid sequelching
      related toxicity in liver cells, we replaced tTA with new non-toxic
      transactivators. By using tTA2, tTA3 and tTA4, we observed tight doxycycline
      dependent gene expression in 23, 49 and 45% of the isolated clones. The tTA4
      vector was used to transduce hepatocytes of mice in vivo. Tight doxycycline
      controllable gene regulation was also observed in the liver of mice, confirming
      our hypothesis that retroviral vectors with autoregulatory loops of the
      tetracycline system facilitate inducible gene expression in the liver in vivo.
      Our new retroviral vector system allows rapid isolation of controllable clones in
      a very high yield and should make the tetracycline system more applicable to
      liver-derived cells and in liver gene therapy in vivo.

PMID- 14966263
TI  - Psoralen interstrand cross-link repair is specifically altered by an adjacent
      triple-stranded structure.
AB  - Targeting DNA-damaging agents to specific DNA sites by using sequence-specific
      DNA ligands has been successful in directing genomic modifications. The
      understanding of repair processing of such targeted damage and the influence of
      the adjacent complex is largely unknown. In this way, directed interstrand cross
      links (ICLs) have already been generated by psoralen targeting. The mechanisms
      responsible for ICL removal are far from being understood in mammalian cells,
      with the proposed involvement of both mutagenic and recombinogenic pathways.
      Here, a unique ICL was introduced at a selected site by photoactivation of a
      psoralen moiety with the use of psoralen conjugates of triplex-forming
      oligonucleotides. The processing of psoralen ICL was evaluated in vitro and in
      cells for two types of cross-linked substrates, either containing a psoralen ICL
      alone or with an adjacent triple-stranded structure. We show that the presence of
      a neighbouring triplex structure interferes with different stages of psoralen ICL
      processing: (i) the ICL-induced DNA repair synthesis in HeLa cell extracts is
      inhibited by the triplex structure, as measured by the efficiency of 'true' and
      futile repair synthesis, stopping at the ICL site; (ii) in HeLa cells, the ICL
      removal via a nucleotide excision repair (NER) pathway is delayed in the presence
      of a neighbouring triplex; and (iii) the binding to ICL of recombinant xeroderma
      pigmentosum A protein, which is involved in pre-incision recruitment of NER
      factors is impaired by the presence of the third DNA strand. These data
      characterize triplex-induced modulation of ICL repair pathways at specific steps,
      which might have implications for the controlled induction of targeted genomic
      modifications and for the associated cellular responses.

PMID- 14966264
TI  - Enhanced gene silencing of HIV-1 specific siRNA using microRNA designed hairpins.
AB  - Post-transcriptional inhibition of HIV-1 replication can be achieved by RNA
      interference (RNAi). The cellular expression of short interfering RNA (siRNA) or
      short hairpin RNA (shRNA) homologous to regions of the HIV-1 genome decreases
      viral replication by the selective degradation of targeted RNA. Here, we
      demonstrate that another class of noncoding regulatory RNA, termed microRNA
      (miRNA), can be used to deliver antiviral RNAi. By incorporating sequences
      encoding siRNA targeting the HIV-1 transactivator protein tat into a human miR-30
      pre-microRNA (pre-miRNA) backbone, we were able to express tat siRNA in cells.
      The tat siRNA delivered as pre-miRNA precursor was 80% more effective in reducing
      HIV-1 p24 antigen production than tat siRNA expressed as conventional shRNA. Our
      results confirm the utility of expressing HIV-1 specific siRNA through a miR-30
      precursor stem-loop structure and suggest that this strategy can be used to
      increase the antiviral potency of RNAi.

PMID- 14966265
TI  - ATM and the catalytic subunit of DNA-dependent protein kinase activate NF-kappaB
      through a common MEK/extracellular signal-regulated kinase/p90(rsk) signaling
      pathway in response to distinct forms of DNA damage.
AB  - We have identified a novel pathway of ataxia telangiectasia mutated (ATM) and DNA
      dependent protein kinase (DNA-PK) signaling that results in nuclear factor kappaB
      (NF-kappaB) activation and chemoresistance in response to DNA damage. We show
      that the anthracycline doxorubicin (DOX) and its congener N-benzyladriamycin (AD
      288) selectively activate ATM and DNA-PK, respectively. Both ATM and DNA-PK
      promote sequential activation of the mitogen-activated protein kinase
      (MAPK)/p90(rsk) signaling cascade in a p53-independent fashion. In turn, p90(rsk)
      interacts with the IkappaB kinase 2 (IKK-2) catalytic subunit of IKK, thereby
      inducing NF-kappaB activity and cell survival. Collectively, our findings suggest
      that distinct members of the phosphatidylinositol kinase family activate a common
      prosurvival MAPK/IKK/NF-kappaB pathway that opposes the apoptotic response
      following DNA damage.

PMID- 14966266
TI  - Cyclic AMP-dependent protein kinase regulates the subcellular localization of
      Snf1-Sip1 protein kinase.
AB  - The Snf1/AMP-activated protein kinase family has diverse roles in cellular
      responses to metabolic stress. In Saccharomyces cerevisiae, Snf1 protein kinase
      has three isoforms of the beta subunit that confer versatility on the kinase and
      that exhibit distinct patterns of subcellular localization. The Sip1 beta subunit
      resides in the cytosol in glucose-grown cells and relocalizes to the vacuolar
      membrane in response to carbon stress. We show that translation of Sip1 initiates
      at the second ATG of the open reading frame, yielding a potential site for N
      myristoylation, and that mutation of the critical glycine abolishes
      relocalization. We further show that the cyclic AMP-dependent protein kinase
      (protein kinase A [PKA]) pathway maintains the cytoplasmic localization of Sip1
      in glucose-grown cells. The Snf1 catalytic subunit also exhibits aberrant
      localization to the vacuolar membrane in PKA-deficient cells, indicating that PKA
      regulates the localization of Snf1-Sip1 protein kinase. These findings establish
      a novel mechanism of regulation of Snf1 protein kinase by the PKA pathway.

PMID- 14966267
TI  - The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2
      and plays an integral role in insulin signal transduction.
AB  - Insulin stimulation of target cells elicits a burst of H(2)O(2) that enhances
      tyrosine phosphorylation of the insulin receptor and its cellular substrate
      proteins as well as distal signaling events in the insulin action cascade. The
      molecular mechanism coupling the insulin receptor with the cellular oxidant
      generating apparatus has not been elucidated. Using reverse transcription-PCR and
      Northern blot analyses, we found that Nox4, a homolog of gp91phox, the phagocytic
      NAD(P)H oxidase catalytic subunit, is prominently expressed in insulin-sensitive
      adipose cells. Adenovirus-mediated expression of Nox4 deletion constructs lacking
      NAD(P)H or FAD/NAD(P)H cofactor binding domains acted in a dominant-negative
      fashion in differentiated 3T3-L1 adipocytes and attenuated insulin-stimulated
      H(2)O(2) generation, insulin receptor (IR) and IRS-1 tyrosine phosphorylation,
      activation of downstream serine kinases, and glucose uptake. Transfection of
      specific small interfering RNA oligonucleotides reduced Nox4 protein abundance
      and also inhibited the insulin signaling cascade. Overexpression of Nox4 also
      significantly reversed the inhibition of insulin-stimulated IR tyrosine
      phosphorylation induced by coexpression of PTP1B by inhibiting PTP1B catalytic
      activity. These data suggest that Nox4 provides a novel link between the IR and
      the generation of cellular reactive oxygen species that enhance insulin signal
      transduction, at least in part via the oxidative inhibition of cellular protein
      tyrosine phosphatases (PTPases), including PTP1B, a PTPase that has been
      previously implicated in the regulation of insulin action.

PMID- 14966268
TI  - An intronic enhancer regulates splicing of the twintron of Drosophila
      melanogaster prospero pre-mRNA by two different spliceosomes.
AB  - We have examined the alternative splicing of the Drosophila melanogaster prospero
      twintron, which contains splice sites for both the U2- and U12-type spliceosome
      and generates two forms of mRNA, pros-L (U2-type product) and pros-S (U12-type
      product). We find that twintron splicing is developmentally regulated: pros-L is
      abundant in early embryogenesis while pros-S displays the opposite pattern. We
      have established a Kc cell in vitro splicing system that accurately splices a
      minimal pros substrate containing the twintron and have examined the sequence
      requirements for pros twintron splicing. Systematic deletion and mutation
      analysis of intron sequences established that twintron splicing requires a 46
      nucleotide purine-rich element located 32 nucleotides downstream of the U2-type
      5' splice site. While this element regulates both splicing pathways, its
      alteration showed the severest effects on the U2-type splicing pathway. Addition
      of an RNA competitor containing the wild-type purine-rich element to the Kc
      extract abolished U2-type splicing and slightly repressed U12-type splicing,
      suggesting that a trans-acting factor(s) binds the enhancer element to stimulate
      twintron splicing. Thus, we have identified an intron region critical for
      prospero twintron splicing as a first step towards elucidating the molecular
      mechanism of splicing regulation involving competition between the two kinds of
      spliceosomes.

PMID- 14966269
TI  - The scl +18/19 stem cell enhancer is not required for hematopoiesis:
      identification of a 5' bifunctional hematopoietic-endothelial enhancer bound by
      Fli-1 and Elf-1.
AB  - Analysis of cis-regulatory elements is central to understanding the genomic
      program for development. The scl/tal-1 transcription factor is essential for
      lineage commitment to blood cell formation and previous studies identified an scl
      enhancer (the +18/19 element) which was sufficient to target the vast majority of
      hematopoietic stem cells, together with hematopoietic progenitors and
      endothelium. Moreover, expression of scl under control of the +18/19 enhancer
      rescued blood progenitor formation in scl(-/-) embryos. However, here we
      demonstrate by using a knockout approach that, within the endogenous scl locus,
      the +18/19 enhancer is not necessary for the initiation of scl transcription or
      for the formation of hematopoietic cells. These results led to the identification
      of a bifunctional 5' enhancer (-3.8 element), which targets expression to
      hematopoietic progenitors and endothelium, contains conserved critical Ets sites,
      and is bound by Ets family transcription factors, including Fli-1 and Elf-1.
      These data demonstrate that two geographically distinct but functionally related
      enhancers regulate scl transcription in hematopoietic progenitors and endothelial
      cells and suggest that enhancers with dual hematopoietic-endothelial activity may
      represent a general strategy for regulating blood and endothelial development.

PMID- 14966270
TI  - Structural and functional conservation of the NuA4 histone acetyltransferase
      complex from yeast to humans.
AB  - The NuA4 histone acetyltransferase (HAT) multisubunit complex is responsible for
      acetylation of histone H4 and H2A N-terminal tails in yeast. Its catalytic
      component, Esa1, is essential for cell cycle progression, gene-specific
      regulation and has been implicated in DNA repair. Almost all NuA4 subunits have
      clear homologues in higher eukaryotes, suggesting that the complex is conserved
      throughout evolution to metazoans. We demonstrate here that NuA4 complexes are
      indeed present in human cells. Tip60 and its splice variant Tip60b/PLIP were
      purified as stable HAT complexes associated with identical polypeptides, with 11
      of the 12 proteins being homologs of yeast NuA4 subunits. This indicates a highly
      conserved subunit composition and the identified human proteins underline the
      role of NuA4 in the control of mammalian cell proliferation. ING3, a member of
      the ING family of growth regulators, links NuA4 to p53 function which we
      confirmed in vivo. Proteins specific to the human NuA4 complexes include ruvB
      like helicases and a bromodomain-containing subunit linked to ligand-dependent
      transcription activation by the thyroid hormone receptor. We also demonstrate
      that subunits MRG15 and DMAP1 are present in distinct protein complexes harboring
      histone deacetylase and SWI2-related ATPase activities, respectively. Finally,
      analogous to yeast, a recombinant trimeric complex formed by Tip60, EPC1, and
      ING3 is sufficient to reconstitute robust nucleosomal HAT activity in vitro. In
      conclusion, the NuA4 HAT complex is highly conserved in eukaryotes, in which it
      plays primary roles in transcription, cellular response to DNA damage, and cell
      cycle control.

PMID- 14966271
TI  - Architectural arrangement of cloned proximal sequence element-binding protein
      subunits on Drosophila U1 and U6 snRNA gene promoters.
AB  - Transcription of snRNA genes by either RNA polymerase II (U1 to U5) or RNA
      polymerase III (U6) is dependent upon a proximal sequence element (PSE) located
      approximately 40 to 60 bp upstream of the transcription start site. In Drosophila
      melanogaster, RNA polymerase specificity is determined by as few as three
      nucleotide differences within the otherwise well-conserved 21-bp PSE. Previous
      photo-cross-linking studies revealed that the D. melanogaster PSE-binding
      protein, DmPBP, contains three subunits (DmPBP45, DmPBP49, and DmPBP95) that
      associate with the DNA to form complexes that are conformationally distinct
      depending upon whether the protein is bound to a U1 or a U6 PSE. We have
      identified and cloned the genes that code for these subunits of DmPBP by virtue
      of their similarity to three of the five subunits of SNAP(c), the human PBP. When
      expressed in S2 cells, each of the three cloned gene products is incorporated
      into a protein complex that functionally binds to a PSE. We also find that the
      conformational difference referred to above is particularly pronounced for
      DmPBP45, herein identified as the ortholog of human SNAP43. DmPBP45 cross-linked
      strongly to DNA for two turns of the DNA helix downstream of the U1 PSE, but it
      cross-linked strongly for only a half turn of the helix downstream of a U6 PSE.
      These substantial differences in the cross-linking pattern are consistent with
      those of a model in which conformational differences in DmPBP-DNA complexes lead
      to selective RNA polymerase recruitment to U1 and U6 promoters.

PMID- 14966272
TI  - Differential and common leukemogenic potentials of multiple NUP98-Hox fusion
      proteins alone or with Meis1.
AB  - NUP98-Hox fusion genes are newly identified oncogenes isolated in myeloid
      leukemias. Intriguingly, only Abd-B Hox genes have been reported as fusion
      partners, indicating that they may have unique overlapping leukemogenic
      properties. To address this hypothesis, we engineered novel NUP98 fusions with
      Hox genes not previously identified as fusion partners: the Abd-B-like gene
      HOXA10 and two Antennepedia-like genes, HOXB3 and HOXB4. Notably, NUP98-HOXA10
      and NUP98-HOXB3 but not NUP98-HOXB4 induced leukemia in a murine transplant
      model, which is consistent with the reported leukemogenic potential ability of
      HOXA10 and HOXB3 but not HOXB4. Thus, the ability of Hox genes to induce leukemia
      as NUP98 fusion partners, although apparently redundant for Abd-B-like activity,
      is not restricted to this group, but rather is determined by the intrinsic
      leukemogenic potential of the Hox partner. We also show that the potent
      leukemogenic activity of Abd-B-like Hox genes is correlated with their strong
      ability to block hematopoietic differentiation. Conversely, coexpression of the
      Hox cofactor Meis1 alleviated the requirement of a strong intrinsic Hox
      transforming potential to induce leukemia. Our results support a model in which
      many if not all Hox genes can be leukemogenic and point to striking functional
      overlap not previously appreciated, presumably reflecting common regulated
      pathways.

PMID- 14966273
TI  - Differential roles of insulin receptor substrates in brown adipocyte
      differentiation.
AB  - Insulin promotes adipocyte differentiation via a complex signaling network
      involving multiple insulin receptor substrates (IRSs). In cultured brown
      preadipocytes, expression of IRS-1 and IRS-2 mRNAs and proteins was at relatively
      high levels before and after differentiation into mature fat cells, while IRS-3
      transcript was not detectable in preadipocytes but increased during the course of
      differentiation, and IRS-4 mRNA was barely detected in both states. To determine
      more precisely the roles of various IRS proteins in adipogenesis, we established
      and characterized brown preadipocyte cell lines from wild-type and IRS knockout
      (KO) animals. While wild-type, IRS-2 KO, and IRS-4 KO cells fully differentiated
      into mature adipocytes, IRS-3 KO cells showed a moderate defect in
      differentiation and IRS-1 KO cells exhibited a severe defect in the process.
      Cells lacking both IRS-1 and IRS-3 completely failed to differentiate. Expression
      of the adipogenic markers peroxisome proliferator-activated receptor gamma
      (PPARgamma), CCAAT/enhancer-binding protein alpha, fatty acid synthase, glucose
      transporter 4, and the transcription factor signal transducer and activator of
      transcription 5, as well as the brown-fat-specific markers PPARgamma coactivator
      1 alpha and uncoupling protein 1, mirrored the differentiation pattern.
      Reconstitution of the IRS-1 KO cells with IRS-1 and IRS-4, but not IRS-2 or IRS
      3, compensated for the lack of differentiation in IRS-1 KO cells. A chimeric
      molecule containing the N terminus of IRS-1 and the C terminus of IRS-2, but not
      one with the N terminus of IRS-2 and the C terminus of IRS-1, also rescued
      differentiation. Expression of Wnt 10a, a molecule known to inhibit adipogenesis,
      was dramatically increased in the IRS-1 KO cells, and this could be reduced by
      overexpression of IRS-1 or IRS-4, which was correlated with restoration of
      differentiation. These data indicate that both IRS-1 and -3 play important roles
      in the differentiation of brown adipocytes and that the N terminus of IRS-1 is
      more important for this function of the molecule. Although IRS-4 is not essential
      for the process, overexpression of IRS-4 can compensate for the deficiency in
      differentiation in IRS-1 KO cells.

PMID- 14966274
TI  - Replication protein A (RPA) phosphorylation prevents RPA association with
      replication centers.
AB  - Mammalian replication protein A (RPA) undergoes DNA damage-dependent
      phosphorylation at numerous sites on the N terminus of the RPA2 subunit. To
      understand the functional significance of RPA phosphorylation, we expressed RPA2
      variants in which the phosphorylation sites were converted to aspartate (RPA2(D))
      or alanine (RPA2(A)). Although RPA2(D) was incorporated into RPA heterotrimers
      and supported simian virus 40 DNA replication in vitro, the RPA2(D) mutant was
      selectively unable to associate with replication centers in vivo. In cells
      containing greatly reduced levels of endogenous RPA2, RPA2(D) again did not
      localize to replication sites, indicating that the defect in supporting
      chromosomal DNA replication is not due to competition with the wild-type protein.
      Use of phosphospecific antibodies demonstrated that endogenous
      hyperphosphorylated RPA behaves similarly to RPA2(D). In contrast, under DNA
      damage or replication stress conditions, RPA2(D), like RPA2(A) and wild-type
      RPA2, was competent to associate with DNA damage foci as determined by
      colocalization with gamma-H2AX. We conclude that RPA2 phosphorylation prevents
      RPA association with replication centers in vivo and potentially serves as a
      marker for sites of DNA damage.

PMID- 14966275
TI  - Functional subdomain in the ankyrin domain of tankyrase 1 required for poly(ADP
      ribosyl)ation of TRF1 and telomere elongation.
AB  - In human cells, telomere elongation by telomerase is repressed in cis by the
      telomeric protein TRF1. Tankyrase 1 binds TRF1 via its ankyrin domain and
      poly(ADP-ribosyl)ates it. Overexpression of tankyrase 1 in telomerase-positive
      cells releases TRF1 from telomeres, resulting in telomere elongation. The
      tankyrase 1 ankyrin domain is classified into five conserved subdomains, ARCs
      (ankyrin repeat clusters) I to V. Here, we investigated the biological
      significance of the ARCs. First, each ARC worked as an independent binding site
      for TRF1. Second, ARCs II to V recognized the N-terminal acidic domain of TRF1
      whereas ARC I bound a discrete site between the homodimerization and the Myb-like
      domains of TRF1. Inactivation of TRF1 binding in the C-terminal ARC, ARC V,
      either by deletion or point mutation, significantly reduced the ability of
      tankyrase 1 to poly(ADP-ribosyl)ate TRF1, release TRF1 from telomeres, and
      elongate telomeres. In contrast, other ARCs, ARC II and/or IV, inactivated by
      point mutations still retained the biological function of tankyrase 1. On the
      other hand, ARC V per se was not sufficient for telomere elongation, suggesting a
      structural role for multiple ARCs. This work provides evidence that specific ARC
      TRF1 interactions play roles in the essential catalytic function of tankyrase 1.

PMID- 14966276
TI  - Barrier proteins remodel and modify chromatin to restrict silenced domains.
AB  - Transcriptionally active and inactive domains are frequently found adjacent to
      one another in the eukaryotic nucleus. To better understand the underlying
      mechanisms by which domains maintain opposing transcription patterns, we
      performed a systematic genomewide screen for proteins that may block the spread
      of silencing in yeast. This analysis identified numerous proteins with efficient
      silencing blocking activities, and some of these have previously been shown to be
      involved in chromatin dynamics. We isolated subunits of Swi/Snf, mediator, and
      TFIID, as well as subunits of the Sas-I, SAGA, NuA3, NuA4, Spt10p, Rad6p, and
      Dot1p complexes, as barrier proteins. We demonstrate that histone acetylation and
      chromatin remodeling occurred at the barrier and correlated with a block to the
      spread of silencing. Our data suggest that multiple overlapping mechanisms were
      involved in delimiting silenced and active domains in vivo.

PMID- 14966277
TI  - DNA methylation may restrict but does not determine differential gene expression
      at the Sgy/Tead2 locus during mouse development.
AB  - Soggy (Sgy) and Tead2, two closely linked genes with CpG islands, were
      coordinately expressed in mouse preimplantation embryos and embryonic stem (ES)
      cells but were differentially expressed in differentiated cells. Analysis of
      established cell lines revealed that Sgy gene expression could be fully repressed
      by methylation of the Sgy promoter and that DNA methylation acted synergistically
      with chromatin deacetylation. Differential gene expression correlated with
      differential DNA methylation, resulting in sharp transitions from methylated to
      unmethylated DNA at the open promoter in both normal cells and tissues, as well
      as in established cell lines. However, neither promoter was methylated in normal
      cells and tissues even when its transcripts were undetectable. Moreover, the Sgy
      promoter remained unmethylated as Sgy expression was repressed during ES cell
      differentiation. Therefore, DNA methylation was not the primary determinant of
      Sgy/Tead2 expression. Nevertheless, Sgy expression was consistently restricted to
      basal levels whenever downstream regulatory sequences were methylated, suggesting
      that DNA methylation restricts but does not regulate differential gene expression
      during mouse development.

PMID- 14966278
TI  - Accelerated response of the myogenin gene to denervation in mutant mice lacking
      phosphorylation of myogenin at threonine 87.
AB  - Gene expression in skeletal muscle is regulated by a family of myogenic basic
      helix-loop-helix (bHLH) proteins. The binding of these bHLH proteins, notably
      MyoD and myogenin, to E-boxes in their own regulatory regions is blocked by
      protein kinase C (PKC)-mediated phosphorylation of a single threonine residue in
      their basic region. Because electrical stimulation increases PKC activity in
      skeletal muscle, these data have led to an attractive model suggesting that
      electrical activity suppresses gene expression by stimulating phosphorylation of
      this critical threonine residue in myogenic bHLH proteins. We show that
      electrical activity stimulates phosphorylation of myogenin at threonine 87 (T87)
      in vivo and that calmodulin-dependent kinase II (CaMKII), as well as PKC,
      catalyzes this reaction in vitro. We find that phosphorylation of myogenin at T87
      is dispensable for skeletal muscle development. We show, however, that the
      decrease in myogenin (myg) expression following innervation is delayed and that
      the increase in expression following denervation is accelerated in mutant mice
      lacking phosphorylation of myogenin at T87. These data indicate that two distinct
      innervation-dependent mechanisms restrain myogenin activity: an inactivation
      mechanism mediated by phosphorylation of myogenin at T87, and a second, novel
      regulatory mechanism that regulates myg gene activity independently of T87
      phosphorylation.

PMID- 14966279
TI  - Persistent signaling by dysregulated thrombin receptor trafficking promotes
      breast carcinoma cell invasion.
AB  - Increased expression of protease-activated receptor 1 (PAR1), a G protein-coupled
      receptor for thrombin, has previously been correlated with breast carcinoma cell
      invasion. PAR1 is irreversibly proteolytically activated, internalized, and
      sorted directly to lysosomes, a critical process for the termination of
      signaling. We determined that activated PAR1 trafficking is severely altered in
      metastatic breast carcinoma cells but not in nonmetastatic or normal breast
      epithelial cells. Consequently, the proteolytically activated receptor is not
      sorted to lysosomes and degraded. Altered trafficking of proteolytically
      activated PAR1 caused sustained activation of phosphoinositide hydrolysis and
      extracellular signal-regulated kinase signaling, even after thrombin withdrawal,
      and enhanced cellular invasion. Thus, our results reveal that a novel alteration
      in trafficking of activated PAR1 causes persistent signaling and, in addition to
      other processes and proteins, contributes to breast carcinoma cell invasion.

PMID- 14966280
TI  - Casein kinase Iepsilon modulates the signaling specificities of dishevelled.
AB  - Wnt signaling is critical to many aspects of development, and aberrant activation
      of the Wnt signaling pathway can cause cancer. Dishevelled (Dvl) protein plays a
      central role in this pathway by transducing the signal from the Wnt receptor
      complex to the beta-catenin destruction complex. Dvl also plays a pivotal role in
      the planar cell polarity pathway that involves the c-Jun N-terminal kinase (JNK).
      How functions of Dvl are regulated in these two distinct pathways is not clear.
      We show that deleting the C-terminal two-thirds of Dvl, which includes the PDZ
      and DEP domains and is essential for Dvl-induced JNK activation, rendered the
      molecule a much more potent activator of the beta-catenin pathway. We also found
      that casein kinase Iepsilon (CKIepsilon), a previously identified positive
      regulator of Wnt signaling, stimulated Dvl activity in the Wnt pathway, but
      dramatically inhibited Dvl activity in the JNK pathway. Consistent with this,
      overexpression of CKIepsilon in Drosophila melanogaster stimulated Wnt signaling
      and disrupted planar cell polarity. We also observed a correlation between the
      localization and the signaling activity of Dvl in the beta-catenin pathway and
      the JNK pathway. Furthermore, by using RNA interference, we demonstrate that the
      Drosophila CKIepsilon homologue Double time positively regulates the beta-catenin
      pathway through Dvl and negatively regulates the Dvl-induced JNK pathway. We
      suggest that CKIepsilon functions as a molecular switch to direct Dvl from the
      JNK pathway to the beta-catenin pathway, possibly by altering the conformation of
      the C terminus of Dvl.

PMID- 14966281
TI  - Biochemical characterization of the Drosophila wingless signaling pathway based
      on RNA interference.
AB  - Regulation of Armadillo (Arm) protein levels through ubiquitin-mediated
      degradation plays a central role in the Wingless (Wg) signaling. Although zeste
      white3 (Zw3)-mediated Arm phosphorylation has been implicated in its degradation,
      we have recently shown that casein kinase Ialpha (CKIalpha) also phosphorylates
      Arm and induces its degradation. However, it remains unclear how CKIalpha and
      Zw3, as well as other components of the Arm degradation complex, regulate Arm
      phosphorylation in response to Wg. In particular, whether Wg signaling suppresses
      CKIalpha- or Zw3-mediated Arm phosphorylation in vivo is unknown. To clarify
      these issues, we performed a series of RNA interference (RNAi)-based analyses in
      Drosophila S2R+ cells by using antibodies that specifically recognize Arm
      phosphorylated at different serine residues. These analyses revealed that Arm
      phosphorylation at serine-56 and at threonine-52, serine-48, and serine-44, is
      mediated by CKIalpha and Zw3, respectively, and that Zw3-directed Arm
      phosphorylation requires CKIalpha-mediated priming phosphorylation. Daxin
      stimulates Zw3- but not CKIalpha-mediated Arm phosphorylation. Wg suppresses Zw3-
      but not CKIalpha-mediated Arm phosphorylation, indicating that a vital regulatory
      step in Wg signaling is Zw3-mediated Arm phosphorylation. In addition, further
      RNAi-based analyses of the other aspects of the Wg pathway clarified that Wg
      induced Dishevelled phosphorylation is due to CKIalpha and that presenilin and
      protein kinase A play little part in the regulation of Arm protein levels in
      Drosophila tissue culture cells.

PMID- 14966282
TI  - Defects in translational regulation mediated by the alpha subunit of eukaryotic
      initiation factor 2 inhibit antiviral activity and facilitate the malignant
      transformation of human fibroblasts.
AB  - Suppression of protein synthesis through phosphorylation of the translation
      initiation factor alpha subunit of eukaryotic initiation factor 2 (eIF2alpha) is
      known to occur in response to many forms of cellular stress. To further study
      this, we have developed novel cell lines that inducibly express FLAG-tagged
      versions of either the phosphomimetic eIF2alpha variant, eIF2alpha-S51D, or the
      phosphorylation-insensitive eIF2alpha-S51A. These variants showed authentic
      subcellular localization, were incorporated into endogenous ternary complexes,
      and were able to modulate overall rates of protein synthesis as well as influence
      cell division. However, phosphorylation of eIF2alpha failed to induce cell death
      or sensitize cells to killing by proapoptotic stimuli, though it was able to
      inhibit viral replication, confirming the role of eIF2alpha in host defense.
      Further, although the eIF2alpha-S51A variant has been shown to transform NIH 3T3
      cells, it was unable to transform the murine fibroblast 3T3 L1 cell line. To
      therefore clarify this issue, we explored the role of eIF2alpha in growth control
      and demonstrated that the eIF2alpha-S51A variant is capable of collaborating with
      hTERT and the simian virus 40 large T antigen in the transformation of primary
      human kidney cells. Thus, dysregulation of translation initiation is indeed
      sufficient to cooperate with defined oncogenic elements and participate in the
      tumorigenesis of human tissue.

PMID- 14966283
TI  - A microdomain formed by the extracellular ends of the transmembrane domains
      promotes activation of the G protein-coupled alpha-factor receptor.
AB  - The alpha-factor receptor (Ste2p) that promotes mating in Saccharomyces
      cerevisiae is similar to other G protein-coupled receptors (GPCRs) in that it
      contains seven transmembrane domains. Previous studies suggested that the
      extracellular ends of the transmembrane domains are important for Ste2p function,
      so a systematic scanning mutagenesis was carried out in which 46 residues near
      the ends of transmembrane domains 1, 2, 3, 4, and 7 were replaced with cysteine.
      These mutants complement mutations constructed previously near the ends of
      transmembrane domains 5 and 6 to analyze all the extracellular ends. Eight new
      mutants created in this study were partially defective in signaling (V45C, N46C,
      T50C, A52C, L102C, N105C, L277C, and A281C). Treatment with 2-([biotinoyl] amino)
      ethyl methanethiosulfonate, a thiol-specific reagent that reacts with accessible
      cysteine residues but not membrane-embedded cysteines, identified a drop in the
      level of reactivity over a consecutive series of residues that was inferred to be
      the membrane boundary. An unusual prolonged zone of intermediate reactivity near
      the extracellular end of transmembrane domain 2 suggests that this region may
      adopt a special structure. Interestingly, residues implicated in ligand binding
      were mainly accessible, whereas residues involved in the subsequent step of
      promoting receptor activation were mainly inaccessible. These results define a
      receptor microdomain that provides an important framework for interpreting the
      mechanisms by which functionally important residues contribute to ligand binding
      and activation of Ste2p and other GPCRs.

PMID- 14966284
TI  - General transcriptional coactivator PC4 activates p53 function.
AB  - The function of p53 is modulated by several transcriptional coactivators that
      regulate its tumor suppressor activity. Here we report that human transcriptional
      coactivator PC4 enhances the DNA binding of p53 to its cognate site in vitro and
      directly interacts with p53 in vivo. In vitro interaction studies demonstrated
      that the C-terminal 30 amino acids (364 to 393) of p53 strongly interact with
      PC4. Surprisingly, PC4 also stimulates the sequence-specific DNA binding of p53
      with the C-terminal 30 amino acids deleted (p53Delta30), suggesting that PC4
      mediates enhancement of p53 DNA binding by a unique mechanism. We also
      demonstrated that PC4 can stimulate p53- and p53Delta30-mediated transactivation
      from a p53-responsive promoter. Furthermore, PC4 enhances p53- and p53Delta30
      dependent apoptosis by inducing bax (a p53-targeted proapoptotic gene) gene
      expression. These results establish the first physiological role of PC4 as a
      transcriptional coactivator.

PMID- 14966285
TI  - Null mutation of the Lmo4 gene or a combined null mutation of the Lmo1/Lmo3 genes
      causes perinatal lethality, and Lmo4 controls neural tube development in mice.
AB  - The LIM-only family of proteins comprises four members; two of these (LMO1 and
      LMO2) are involved in human T-cell leukemia via chromosomal translocations, and
      LMO2 is a master regulator of hematopoiesis. We have carried out gene targeting
      of the other members of the LIM-only family, viz., genes Lmo1, Lmo3 and Lmo4, to
      investigate their role in mouse development. None of these genes has an
      obligatory role in lymphopoiesis. In addition, while null mutations of Lmo1 or
      Lmo3 have no discernible phenotype, null mutation of Lmo4 alone causes perinatal
      lethality due to a severe neural tube defect which occurs in the form of
      anencephaly or exencephaly. Since the Lmo1 and Lmo3 gene sequences are highly
      related and have partly overlapping expression domains, we assessed the effect of
      compound Lmo1/Lmo3 null mutations. Although no anatomical defects were apparent
      in compound null pups, these animals also die within 24 h of birth, suggesting
      that a compensation between the related Lmo1 and 3 proteins can occur during
      embryogenesis to negate the individual loss of these genes. Our results complete
      the gene targeting of the LIM-only family in mice and suggest that all four
      members of this family are important in regulators of distinct developmental
      pathways.

PMID- 14966286
TI  - Defective neural tube closure and anteroposterior patterning in mice lacking the
      LIM protein LMO4 or its interacting partner Deaf-1.
AB  - LMO4 belongs to a family of transcriptional regulators that comprises two zinc
      binding LIM domains. LIM-only (LMO) proteins appear to function as docking sites
      for other factors, leading to the assembly of multiprotein complexes. The
      transcription factor Deaf-1/NUDR has been identified as one partner protein of
      LMO4. We have disrupted the Lmo4 and Deaf-1 genes in mice to define their
      biological function in vivo. All Lmo4 mutants died shortly after birth and showed
      defects within the presphenoid bone, with 50% of mice also exhibiting
      exencephaly. Homeotic transformations were observed in Lmo4-null embryos and
      newborn mice, but with incomplete penetrance. These included skeletal defects in
      cervical vertebrae and the rib cage. Furthermore, fusions of cranial nerves IX
      and X and defects in cranial nerve V were apparent in some Lmo4(-/-) and Lmo4(+/
      ) mice. Remarkably, Deaf-1 mutants displayed phenotypic abnormalities similar to
      those observed in Lmo4 mutants. These included exencephaly, transformation of
      cervical segments, and rib cage abnormalities. In contrast to Lmo4 nullizygous
      mice, nonexencephalic Deaf-1 mutants remained healthy. No defects in the sphenoid
      bone or cranial nerves were apparent. Thus, Lmo4 and Deaf-1 mutant mice exhibit
      overlapping as well as distinct phenotypes. Our data indicate an important role
      for these two transcriptional regulators in pathways affecting neural tube
      closure and skeletal patterning, most likely reflecting their presence in a
      functional complex in vivo.

PMID- 14966287
TI  - Id2 is dispensable for Myc-induced epidermal neoplasia.
AB  - We have previously described a transgenic mouse model of epidermal neoplasia
      wherein expression of a switchable form of c-Myc, MycER(TAM), is targeted to the
      postmitotic suprabasal keratinocytes of murine epidermis via the involucrin
      promoter. Sustained activation of c-MycER(TAM) results in a progressive
      neoplastic phenotype characterized by aberrant ectopic proliferation and delayed
      differentiation of suprabasal keratinocytes, culminating in papillomatosis.
      Transcription of the Id2 gene is regulated by Myc family proteins. Moreover, Id2
      is implicated as a pivotal determinant of cell fate in multiple lineages and has
      a demonstrated role in mediating Myc-dependent cell proliferation in vitro
      through its interaction with retinoblastoma protein. Using Id2 nullizygous mice,
      we assessed in vivo the requirement for Id2 in mediating Myc-induced papilloma
      formation in skin. We show that absence of Id2 has no discernible impact on any
      measurable attribute of Myc function or on the timing or extent of eventual tumor
      formation. Thus, our data argue against any essential role for Id2 in mediating
      Myc action in vivo.

PMID- 14966288
TI  - Cell cycle localization, dimerization, and binding domain architecture of the
      telomere protein cPot1.
AB  - Pot1 is a single-stranded-DNA-binding protein that recognizes telomeric G-strand
      DNA. It is essential for telomere capping in Saccharomyces pombe and regulates
      telomere length in humans. Human Pot1 also interacts with proteins that bind the
      duplex region of the telomeric tract. Thus, like Cdc13 from S. cerevisiae, Pot 1
      may have multiple roles at the telomere. We show here that endogenous chicken
      Pot1 (cPot1) is present at telomeres during periods of the cell cycle when t
      loops are thought to be present. Since cPot1 can bind internal loops and directly
      adjacent DNA-binding sites, it is likely to fully coat and protect both G-strand
      overhangs and the displaced G strand of a t loop. The minimum binding site of
      cPot1 is double that of the S. pombe DNA-binding domain. Although cPot can self
      associate, dimerization is not required for DNA binding and hence does not
      explain the binding-site duplication. Instead, the DNA-binding domain appears to
      be extended to contain a second binding motif in addition to the conserved
      oligonucleotide-oligosaccharide (OB) fold present in other G-strand-binding
      proteins. This second motif could be another OB fold. Although dimerization is
      inefficient in vitro, it may be regulated in vivo and could promote association
      with other telomere proteins and/or telomere compaction.

PMID- 14966289
TI  - Developmentally essential protein flightless I is a nuclear receptor coactivator
      with actin binding activity.
AB  - Hormone-activated nuclear receptors (NR) activate transcription by recruiting
      multiple coactivator complexes to the promoters of target genes. One important
      coactivator complex includes a p160 coactivator (e.g., GRIP1, SRC-1, or ACTR)
      that binds directly to activated NR, the histone acetyltransferase p300 or CBP,
      and the arginine-specific histone methyltransferase CARM1. We previously
      demonstrated that the coactivator function of CARM1 depends both on the
      methyltransferase activity and on additional unknown proteins that bind to CARM1.
      In this study a yeast two-hybrid screen for proteins that bind CARM1 identified
      the protein Flightless I (Fli-I), which has essential roles in Drosophila and
      mouse development. Fli-I bound to CARM1, GRIP1, and NRs and cooperated
      synergistically with CARM1 and GRIP1 to enhance NR function. Fli-I bound poorly
      to and did not cooperate with PRMT1, a CARM1-related protein arginine
      methyltransferase that also functions as an NR coactivator. The synergy between
      GRIP1, CARM1, and Fli-I required the methyltransferase activity of CARM1. The C
      terminal AD1 (binding site for p300/CBP) and AD2 (binding site for CARM1)
      activation domains of GRIP1 contributed to the synergy but were less stringently
      required than the N-terminal region of GRIP1, which is the binding site for Fli
      I. Endogenous Fli-I was recruited to the estrogen-regulated pS2 gene promoter of
      MCF-7 cells in response to the hormone, and reduction of endogenous Fli-I levels
      by small interfering RNA reduced hormone-stimulated gene expression by the
      endogenous estrogen receptor. A fragment of Fli-I that is related to the actin
      binding protein gelsolin enhanced estrogen receptor activity, and mutations that
      reduced actin binding also reduced the coactivator function of this Fli-I
      fragment. These data suggest that Fli-I may facilitate interaction of the p160
      coactivator complex with other coactivators or coactivator complexes containing
      actin or actin-like proteins.

PMID- 14966290
TI  - Formation of boundaries of transcriptionally silent chromatin by nucleosome
      excluding structures.
AB  - The eukaryotic genome is divided into chromosomal domains of distinct gene
      activities. Transcriptionally silent chromatin tends to encroach upon active
      chromatin. Barrier elements that can block the spread of silent chromatin have
      been documented, but the mechanisms of their function are not resolved. We show
      that the prokaryotic LexA protein can function as a barrier to the propagation of
      transcriptionally silent chromatin in yeast. The barrier function of LexA
      correlates with its ability to disrupt local chromatin structure. In accord with
      this, (CCGNN)(n) and poly(dA-dT), both of which do not favor nucleosome
      formation, can also act as efficient boundaries of silent chromatin. Moreover, we
      show that a Rap1p-binding barrier element also disrupts chromatin structure.
      These results demonstrate that nucleosome exclusion is one of the mechanisms for
      the establishment of boundaries of silent chromatin domains.

PMID- 14966291
TI  - Quantitative proteomic identification of six4 as the trex-binding factor in the
      muscle creatine kinase enhancer.
AB  - Transcriptional regulatory element X (Trex) is a positive control site within the
      Muscle creatine kinase (MCK) enhancer. Cell culture and transgenic studies
      indicate that the Trex site is important for MCK expression in skeletal and
      cardiac muscle. After selectively enriching for the Trex-binding factor (TrexBF)
      using magnetic beads coupled to oligonucleotides containing either wild-type or
      mutant Trex sites, quantitative proteomics was used to identify TrexBF as Six4, a
      homeodomain transcription factor of the Six/sine oculis family, from a background
      of approximately 900 copurifying proteins. Using gel shift assays and Six
      specific antisera, we demonstrated that Six4 is TrexBF in mouse skeletal myocytes
      and embryonic day 10 chick skeletal and cardiac muscle, while Six5 is the major
      TrexBF in adult mouse heart. In cotransfection studies, Six4 transactivates the
      MCK enhancer as well as muscle-specific regulatory regions of Aldolase A and
      Cardiac troponin C via Trex/MEF3 sites. Our results are consistent with Six4
      being a key regulator of muscle gene expression in adult skeletal muscle and in
      developing striated muscle. The Trex/MEF3 composite sequence ([C/A]ACC[C/T]GA)
      allowed us to identify novel putative Six-binding sites in six other muscle
      genes. Our proteomics strategy will be useful for identifying transcription
      factors from complex mixtures using only defined DNA fragments for purification.

PMID- 14966292
TI  - Immortalization of human mammary epithelial cells is associated with inactivation
      of the p14ARF-p53 pathway.
AB  - Inactivation of the ARF-p53 tumor suppressor pathway leads to immortalization of
      murine fibroblasts. The role of this pathway in immortalization of human
      epithelial cells is not clear. We analyzed the functionality of the p14(ARF)-p53
      pathway in human mammary epithelial cells (MEC) immortalized by human
      papillomavirus 16 (HPV16) E6, the p53 degradation-defective E6 mutant Y54D, or
      hTERT. E6-MEC or E6Y54D-MEC maintains high-level expression of p14(ARF). Late
      passage hTERT-immortalized MEC express p53 but down-regulate p14(ARF). Enforced
      expression of p14(ARF) induces p53-dependent senescence in hTERT-MEC, while both
      E6-MEC and E6Y54D-MEC are resistant. We show that E6Y54D inhibits p14(ARF)
      induced activation of p53 without inactivation of the p53-dependent DNA damage
      response. Hence, p53 degradation and inhibition of p14(ARF) signaling to p53 are
      independent functions of HPV16 E6. Our observations imply that long-term
      proliferation of MEC requires inactivation of the p14(ARF)-p53 pathway.

PMID- 14966293
TI  - Direct interaction between nucleosome assembly protein 1 and the papillomavirus
      E2 proteins involved in activation of transcription.
AB  - Using a yeast two-hybrid screen, we identified human nucleosome assembly protein
      1 (hNAP-1) as a protein interacting with the activation domain of the
      transcriptional activator encoded by papillomaviruses (PVs), the E2 protein. We
      show that the interaction between E2 and hNAP-1 is direct and not merely mediated
      by the transcriptional coactivator p300, which is bound by both proteins.
      Coexpression of hNAP-1 strongly enhances activation by E2, indicating a
      functional interaction as well. E2 binds to at least two separate domains within
      hNAP-1, one within the C terminus and an internal domain. The binding of E2 to
      hNAP-1 is necessary for cooperativity between the factors. Moreover, the N
      terminal 91 amino acids are crucial for the transcriptional activity of hNAP-1,
      since deletion mutants lacking this N-terminal portion fail to cooperate with E2.
      We provide evidence that hNAP-1, E2, and p300 can form a ternary complex
      efficient in the activation of transcription. We also show that p53 directly
      interacts with hNAP-1, indicating that transcriptional activators in addition to
      PV E2 interact with hNAP-1. These results suggest that the binding of sequence
      specific DNA binding proteins to hNAP-1 may be an important step contributing to
      the activation of transcription.

PMID- 14966294
TI  - A transforming growth factor beta-induced Smad3/Smad4 complex directly activates
      protein kinase A.
AB  - Transforming growth factor beta (TGFbeta) interacts with cell surface receptors
      to initiate a signaling cascade critical in regulating growth, differentiation,
      and development of many cell types. TGFbeta signaling involves activation of Smad
      proteins which directly regulate target gene expression. Here we show that Smad
      proteins also regulate gene expression by using a previously unrecognized pathway
      involving direct interaction with protein kinase A (PKA). PKA has numerous
      effects on growth, differentiation, and apoptosis, and activation of PKA is
      generally initiated by increased cellular cyclic AMP (cAMP). However, we found
      that TGFbeta activates PKA independent of increased cAMP, and our observations
      support the conclusion that there is formation of a complex between Smad proteins
      and the regulatory subunit of PKA, with release of the catalytic subunit from the
      PKA holoenzyme. We also found that the activation of PKA was required for TGFbeta
      activation of CREB, induction of p21(Cip1), and inhibition of cell growth. Taken
      together, these data indicate an important and previously unrecognized
      interaction between the TGFbeta and PKA signaling pathways.

PMID- 14966295
TI  - Control of cyclin G2 mRNA expression by forkhead transcription factors: novel
      mechanism for cell cycle control by phosphoinositide 3-kinase and forkhead.
AB  - Cyclin G2 is an unconventional cyclin highly expressed in postmitotic cells.
      Unlike classical cyclins that promote cell cycle progression, cyclin G2 blocks
      cell cycle entry. Here we studied the mechanisms that regulate cyclin G2 mRNA
      expression during the cell cycle. Analysis of synchronized NIH 3T3 cell cultures
      showed elevated cyclin G2 mRNA expression levels at G(0), with a considerable
      reduction as cells enter cell cycle. Downregulation of cyclin G2 mRNA levels
      requires activation of phosphoinositide 3-kinase, suggesting that this enzyme
      controls cyclin G2 mRNA expression. Because the phosphoinositide 3-kinase pathway
      inhibits the FoxO family of forkhead transcription factors, we examined the
      involvement of these factors in the regulation of cyclin G2 expression. We show
      that active forms of the forkhead transcription factor FoxO3a (FKHRL1) increase
      cyclin G2 mRNA levels. Cyclin G2 has forkhead consensus motifs in its promoter,
      which are transactivated by constitutive active FoxO3a forms. Finally,
      interference with forkhead-mediated transcription by overexpression of an
      inactive form decreases cyclin G2 mRNA expression levels. These results show that
      FoxO genes regulate cyclin G2 expression, illustrating a new role for
      phosphoinositide 3-kinase and FoxO transcription factors in the control of cell
      cycle entry.

PMID- 14966296
TI  - Site-selective regulation of platelet-derived growth factor beta receptor
      tyrosine phosphorylation by T-cell protein tyrosine phosphatase.
AB  - The platelet-derived growth factor (PDGF) beta receptor mediates mitogenic and
      chemotactic signals. Like other tyrosine kinase receptors, the PDGF beta receptor
      is negatively regulated by protein tyrosine phosphatases (PTPs). To explore
      whether T-cell PTP (TC-PTP) negatively regulates the PDGF beta receptor, we
      compared PDGF beta receptor tyrosine phosphorylation in wild-type and TC-PTP
      knockout (ko) mouse embryos. PDGF beta receptors were hyperphosphorylated in TC
      PTP ko embryos. Fivefold-higher ligand-induced receptor phosphorylation was
      observed in TC-PTP ko mouse embryo fibroblasts (MEFs) as well. Reexpression of TC
      PTP partly abolished this difference. As determined with site-specific
      phosphotyrosine antibodies, the extent of hyperphosphorylation varied among
      different autophosphorylation sites. The phospholipase Cgamma1 binding site
      Y1021, previously implicated in chemotaxis, displayed the largest increase in
      phosphorylation. The increase in Y1021 phosphorylation was accompanied by
      increased phospholipase Cgamma1 activity and migratory hyperresponsiveness to
      PDGF. PDGF beta receptor tyrosine phosphorylation in PTP-1B ko MEFs but not in
      PTPepsilon ko MEFs was also higher than that in control cells. This increase
      occurred with a site distribution different from that seen after TC-PTP
      depletion. PDGF-induced migration was not increased in PTP-1B ko cells. In
      summary, our findings identify TC-PTP as a previously unrecognized negative
      regulator of PDGF beta receptor signaling and support the general notion that
      PTPs display site selectivity in their action on tyrosine kinase receptors.

PMID- 14966297
TI  - Human checkpoint protein hRad9 functions as a negative coregulator to repress
      androgen receptor transactivation in prostate cancer cells.
AB  - Positive responses to combined androgen elimination therapy and radiation therapy
      have been well documented in the treatment of prostate cancer patients. The
      detailed mechanisms how androgen-androgen receptor (AR) cross talks to the
      radiation-related signal pathways, however, remain largely unknown. Here we
      report the identification of hRad9, a key member of the checkpoint Rad protein
      family, as a coregulator to suppress androgen-AR transactivation in prostate
      cancer cells. In vivo and in vitro interaction assays using Saccharomyces
      cerevisiae two-hybrid, mammalian two-hybrid, glutathione S-transferase pull-down,
      and coimmunoprecipitation methods prove that AR can interact with the C terminus
      of hRad9 via its ligand binding domain. The FXXLF motif within the C terminus of
      hRad9 interrupts the androgen-induced interaction between the N terminus and C
      terminus of AR. This interaction between AR and hRad9 may result in the
      suppression of AR transactivation, demonstrated by the repressed AR
      transactivation in androgen-induced luciferase reporter assay and the reduced
      endogenous prostate-specific antigen expression in Western blot assay. Addition
      of small interfering RNA of hRad9 can reverse hRad9 suppression effects, which
      suggests that hRad9 functions as a repressor of AR transactivation in vivo.
      Together, our data provide the first linkage between androgen-AR signals and
      radiation-induced responses. Further studies of the influence of hRad9 on
      prostate cancer growth may provide potential new therapeutic approaches.

PMID- 14966298
TI  - Activation of c-fos in GABAergic neurones in the preoptic area during sleep and
      in response to sleep deprivation.
AB  - Neurones in the median preoptic nucleus (MnPN) and the ventrolateral preoptic
      area (vlPOA) express immunoreactivity for c-Fos protein following sustained
      sleep, and display elevated discharge rates during both non-REM and REM sleep
      compared to waking. We evaluated the hypothesis that MnPN and vlPOA sleep-active
      neurones are GABAergic by combining staining for c-Fos protein with staining for
      glutamic acid decarboxylase (GAD). In a group of six rats exhibiting spontaneous
      total sleep times averaging 82.2 +/- 5.1% of the 2 h immediately prior to death,
      >75% of MnPN neurones that were Fos-immunoreactive (IR) were also GAD-IR. Similar
      results were obtained in the vlPOA. In a group of 11 rats exhibiting spontaneous
      sleep times ranging from 20 to 92%, the number of Fos + GAD-IR neurones in MnPN
      and vlPOA was positively correlated with total sleep time. Compared to control
      animals, Fos + GAD-IR cell counts in the MnPN were significantly elevated in rats
      that were sleep deprived for 24 h and permitted 2 h of recovery sleep. These
      findings demonstrate that a majority of MnPN and vlPOA neurones that express Fos
      IR during sustained spontaneous sleep are GABAergic. They also demonstrate that
      sleep deprivation is associated with increased activation of GABAergic neurones
      in the MnPN and vlPOA.

PMID- 14966299
TI  - Over-expression of FK506-binding protein FKBP12.6 alters excitation-contraction
      coupling in adult rabbit cardiomyocytes.
AB  - This study investigated the function of FK506-binding protein (FKBP12.6) using
      adenoviral-mediated gene transfer to over-express FKBP12.6 (Ad-FKBP12.6) in adult
      rabbit ventricular cardiomyocytes. Infection with a beta-galactosidase-expressing
      adenovirus (Ad-LacZ) was used as a control. Peak-systolic intracellular [Ca(2+)]
      (measured with Fura-2) was higher in the Ad-FKBP12.6 group compared to Ad-LacZ (1
      Hz field stimulation at 37 degrees C). The amplitude of caffeine-induced Ca(2+)
      release was also greater, indicating a higher SR Ca(2+) content in the Ad
      FKBP12.6 group. Voltage clamp experiments indicated that FKBP12.6 over-expression
      did not change L-type Ca(2+) current amplitude or Ca(2+) efflux rates via the
      Na(+)-Ca(2+) exchanger. Ca(2+) transients comparable to those after Ad-FKBP12.6
      transfection could be obtained by enhancing SR Ca(2+) content of Ad-LacZ infected
      cells with periods of high frequency stimulation. Line-scan confocal microscopy
      (Fluo-3 fluorescence) of intact cardiomyocytes stimulated at 0.5 Hz (20-21
      degrees C) revealed a higher degree of synchronicity of SR Ca(2+) release and
      fewer non-responsive Ca(2+) release sites in the Ad-FKBP12.6 group compared to
      control. Ca(2+) spark morphology was measured in beta-escin-permeabilized
      cardiomyocytes at a free [Ca(2+)](i) of 150 nm. The average values of the spark
      parameters (amplitude, duration, width and frequency) were reduced in the Ad
      FKBP12.6 group. Increasing [Ca(2+)](i) to 400 nm caused coherent propagating
      Ca(2+) waves in the Ad-FKBP12.6 group but only limited Ca(2+) release events were
      recorded in the control group. These data indicate that FKBP12.6 over-expression
      enhances Ca(2+) transient amplitude predominately by increasing SR Ca(2+)
      content. Moreover, there is also evidence that FKBP12.6 can enhance the coupling
      between SR Ca(2+) release sites independently of SR content.

PMID- 14966300
TI  - Activation of GABA(A) receptors containing the alpha4 subunit by GABA and
      pentobarbital.
AB  - The activation properties of GABA(A) receptors containing alpha4beta2gamma2 and
      alpha4beta2delta subunits were examined in the presence of GABA or pentobarbital.
      The receptors were expressed transiently in HEK 293 cells, and the
      electrophysiological experiments were carried out using cell-attached single
      channel patch clamp or whole-cell macroscopic recordings. The data show that GABA
      is a stronger activator of alpha4beta2gamma2 receptors than alpha4beta2delta
      receptors. Single-channel clusters were recorded from alpha4beta2gamma2 receptors
      in the presence of 10-5000 microm GABA. The maximal intracluster open probability
      was 0.35, with a half-maximal response elicited by 32 microm GABA. Simultaneous
      kinetic analysis of single-channel currents obtained at various GABA
      concentrations yields a channel opening rate constant of 250 s(-1), and a K(D) of
      20 microm. In contrast, only isolated openings were observed in the presence of
      GABA for the alpha4beta2delta receptor. Pentobarbital was a strong activator of
      both alpha4beta2gamma2 and alpha4beta2delta receptors. The maximal cluster open
      probability, recorded in the presence of 100 microm pentobarbital, was 0.7. At
      higher pentobarbital concentrations, the cluster open probability was reduced,
      probably due to channel block. The results from single-channel experiments were
      confirmed by macroscopic recordings from HEK cells in the presence of GABA or
      pentobarbital.

PMID- 14966301
TI  - Nuclear translocation of the transcription factor STAT3 in the guinea pig brain
      during systemic or localized inflammation.
AB  - The purpose of the present study was to investigate a possible lipopolysaccharide
      (LPS)-induced activation of brain cells that is mediated by the pleiotropic
      cytokine interleukin-6 (IL-6) and its transcription factor STAT3 during systemic
      or localized inflammation. In guinea pigs, intra-arterial (i.a., 10 microg x kg(
      1)) or intraperitoneal (i.p., 30 microg x kg(-1)) injections of bacterial LPS
      cause a systemic inflammatory response which is accompanied by a robust fever. A
      febrile response can also be induced by administration of LPS into artificial
      subcutaneously implanted Teflon chambers (s.c. 100 or 10 microg x kg(-1)), which
      reflects an experimental model that mimics local tissue inflammation. Baseline
      plasma levels of bioactive IL-6 determined 60 min prior to injections of LPS or
      vehicle amounted to 35-80 international units (i.u.) ml(-1). Within 90 min of LPS
      injection, plasma IL-6 rose about 1000-fold in the groups injected i.a. or i.p.,
      about 50-fold in the group injected s.c. with 100 microg x kg(-1) LPS, and only 5
      fold in guinea pigs injected with the lower dose of LPS (10 microg x kg(-1)). At
      this time point, a distinct nuclear translocation pattern of the transcription
      factor STAT3 became evident in several brain structures. Amongst those, the
      sensory circumventricular organs known to lack a tight blood-brain barrier such
      as the area postrema, the vascular organ of the lamina terminalis and the
      subfornical organ, as well as the hypothalamic supraoptic nucleus showed intense
      nuclear STAT3 signals in the i.a. or i.p. injected groups. In contrast a moderate
      (s.c. group, 100 microg x kg(-1)), or even no (s.c. group, 10 microg x kg(-1)),
      nuclear STAT3 translocation occurred in response to s.c. injections of LPS. These
      results suggest that STAT3-mediated genomic activation of target gene
      transcription in brain cells occurred only in those cases in which sufficiently
      high concentrations of circulating IL-6 were formed during systemic (i.a. and
      i.p. groups) or localized (s.c. group, 100 microg x kg(-1)) inflammation.

PMID- 14966302
TI  - Capacitance measurements of exocytosis in mouse pancreatic alpha-, beta- and
      delta-cells within intact islets of Langerhans.
AB  - Capacitance measurements of exocytosis were applied to functionally identified
      alpha-, beta- and delta-cells in intact mouse pancreatic islets. The maximum rate
      of capacitance increase in beta-cells during a depolarization to 0 mV was
      equivalent to 14 granules s(-1), <5% of that observed in isolated beta-cells.
      Beta-cell secretion exhibited bell-shaped voltage dependence and peaked at +20
      mV. At physiological membrane potentials (up to approximately -20 mV) the maximum
      rate of release was approximately 4 granules s(-1). Both exocytosis (measured by
      capacitance measurements) and insulin release (detected by radioimmunoassay) were
      strongly inhibited by the L-type Ca(2+) channel blocker nifedipine (25 microm)
      but only marginally (<20%) affected by the R-type Ca(2+) channel blocker SNX482
      (100 nm). Exocytosis in the glucagon-producing alpha-cells peaked at +20 mV. The
      capacitance increases elicited by pulses to 0 mV exhibited biphasic kinetics and
      consisted of an initial transient (150 granules s(-1)) and a sustained late
      component (30 granules s(-1)). Whereas addition of the N-type Ca(2+) channel
      blocker omega-conotoxin GVIA (0.1 microm) inhibited glucagon secretion measured
      in the presence of 1 mm glucose to the same extent as an elevation of glucose to
      20 mm, the L-type Ca(2+) channel blocker nifedipine (25 microm) had no effect.
      Thus, glucagon release during hyperglycaemic conditions depends principally on
      Ca(2+)-influx through N-type rather than L-type Ca(2+) channels. Exocytosis in
      the somatostatin-secreting delta-cells likewise exhibited two kinetically
      separable phases of capacitance increase and consisted of an early rapid (600
      granules s(-1)) component followed by a sustained slower (60 granules s(-1))
      component. We conclude that (1) capacitance measurements in intact pancreatic
      islets are feasible; (2) exocytosis measured in beta-cells in situ is
      significantly slower than that of isolated cells; and (3) the different types of
      islet cells exhibit distinct exocytotic features.

PMID- 14966303
TI  - Modulation of plasma membrane calcium-ATPase activity by local calcium
      microdomains near CRAC channels in human T cells.
AB  - The spatial distribution of Ca(2+) signalling molecules is critical for
      establishing specific interactions that control Ca(2+) signal generation and
      transduction. In many cells, close physical coupling of Ca(2+) channels and their
      targets enables precise and robust activation of effector molecules through local
      [Ca(2+)](i) elevation in microdomains. In T cells, the plasma membrane Ca(2+)
      ATPase (PMCA) is a major target of Ca(2+) influx through Ca(2+) release-activated
      Ca(2+) (CRAC) channels. Elevation of [Ca(2+)](i) slowly modulates pump activity
      to ensure the stability and enhance the dynamic nature of Ca(2+) signals. In this
      study we probed the functional organization of PMCA and CRAC channels in T cells
      by manipulating Ca(2+) microdomains near CRAC channels and measuring the
      resultant modulation of PMCAs. The amplitude and spatial extent of microdomains
      was increased by elevating the rate of Ca(2+) entry, either by raising
      extracellular [Ca(2+)], by increasing the activity of CRAC channels with 2
      aminoethoxyborane (2-APB), or by hyperpolarizing the plasma membrane.
      Surprisingly, doubling the rate of Ca(2+) influx does not further increase global
      [Ca(2+)](i) in a substantial fraction of cells, due to a compensatory increase in
      PMCA activity. The enhancement of PMCA activity without changes in global
      [Ca(2+)](i) suggests that local [Ca(2+)](i) microdomains near CRAC channels
      effectively promote PMCA modulation. These results reveal an intimate functional
      association between CRAC channels and Ca(2+) pumps in the plasma membrane which
      may play an important role in governing the time course and magnitude of Ca(2+)
      signals in T cells.

PMID- 14966304
TI  - Spreading dilatation in rat mesenteric arteries associated with calcium
      independent endothelial cell hyperpolarization.
AB  - Both ACh and levcromakalim evoke smooth muscle cell hyperpolarization and
      associated relaxation in rat mesenteric resistance arteries. We investigated if
      they could evoke conducted vasodilatation along isolated arteries, whether this
      reflected spreading hyperpolarization and the possible mechanism involved. Focal
      micropipette application of either ACh, to stimulate endothelial cell muscarinic
      receptors, or levcromakalim, to activate smooth muscle K(ATP) channels, each
      evoked a local dilatation (88 +/- 14%, n= 6 and 92 +/- 6% reversal of
      phenylephrine-induced tone, n= 11, respectively) that rapidly spread upstream (at
      1.5 mm 46 +/- 19%, n= 6 and 57 +/- 13%, n= 9) to dilate the entire isolated
      artery. The local dilatation to ACh was associated with a rise in endothelial
      cell [Ca(2+)](i) (F/F(t = 0)= 1.22 +/- 0.33, n= 14) which did not spread beyond
      0.5 mm (F/F(t = 0)= 1.01 +/- 0.01, n= 14), while the local dilatation to
      levcromakalim was not associated with any change in endothelial cell [Ca(2+)](i).
      In contrast, ACh and levcromakalim both stimulated local (12.7 +/- 1.2 mV, n= 10
      and 13.5 +/- 4.7 mV, n= 10) and spreading (at 2 mm: 3.0 +/- 1.1 mV, n= 5 and 4.1
      +/- 0.7 mV, n= 5) smooth muscle hyperpolarization. The spread of
      hyperpolarization could be prevented by cutting the artery, so was not due to a
      diffusible agent. Both the spreading dilatation and hyperpolarization were
      endothelium dependent. The injection of propidium iodide into either endothelial
      or smooth muscle cells revealed extensive dye coupling between the endothelial
      cells, but limited coupling between the smooth muscle cells. Some evidence for
      heterocellular spread of dye was also evident. Together, these data show that
      vasodilatation can spread over significant distances in mesenteric resistance
      arteries, and suggest this reflects an effective coupling between the endothelial
      cells to facilitate [Ca(2+)](i)-independent spread of hyperpolarization.

PMID- 14966305
TI  - ATP participates in three excitatory postsynaptic potentials in the submucous
      plexus of the guinea pig ileum.
AB  - Synaptic transmission between neurones intrinsic to the wall of the intestine
      involves multiple neurotransmitters. This study aimed to identify
      neurotransmitters responsible for non-cholinergic excitatory synaptic
      transmission in the submucous plexus of the guinea pig ileum. Intracellular
      recordings were made from secretomotor and vasodilator neurones. A single
      electrical stimulus to a fibre tract evoked excitatory postsynaptic potentials
      (EPSPs) with three different time courses - fast, slow and an EPSP with an
      intermediate time course (latency 96 ms, duration 1.2 s). In all neurones,
      blocking nicotinic receptors reduced fast EPSPs, but they were abolished in only
      57 of 78 neurones. Fast EPSPs were also reduced by P2 purinoceptor blockade (5 of
      27 neurones) or 5-HT(3) receptor blockade (3 of 20 neurones). The intermediate
      EPSP was abolished by P2 receptor blockade (13 of 13 neurones) or by the specific
      P2Y(1) receptor antagonist MRS 2179 (5 of 5 neurones) and was always preceded by
      a nicotinic or mixed nicotinic/purinergic fast EPSP. Intermediate EPSPs were
      observed in over half of all neurones including most non-cholinergic secretomotor
      neurones identified by immunoreactivity for vasoactive intestinal peptide. The
      slow EPSP evoked by a single pulse stimulus was also abolished by P2 receptor
      blockade (5 of 5 neurones) or by MRS 2179 (3 of 3 neurones). We conclude that
      fast EPSPs in submucous neurones are mediated by acetylcholine acting at
      nicotinic receptors, ATP acting at P2X receptors and 5-HT acting at 5-HT(3)
      receptors. Both the intermediate EPSP and the single stimulus slow EPSP are
      mediated by ATP acting at P2Y(1) receptors.

PMID- 14966320
TI  - Quantum crystallography: electron density and bonding, a microsymposium.

PMID- 14966306
TI  - Essential role of troponin I in the positive inotropic response to isoprenaline
      in mouse hearts contracting auxotonically.
AB  - PKA-dependent phosphorylation of cardiac troponin I (cTnI) contributes
      significantly to beta-adrenergic agonist-induced acceleration of myocardial
      relaxation (lusitropy). However, the role of PKA-dependent cTnI phosphorylation
      in the positive inotropic response to beta-adrenergic stimulation is unclear. We
      studied the contractile response to isoprenaline (10 nm) in isolated hearts and
      isolated cardiomyocytes from transgenic mice with cardiac-specific expression of
      slow skeletal TnI (ssTnI, which lacks the N-terminal protein extension containing
      PKA-sensitive phosphorylation sites in cTnI) and matched wild-type littermate
      controls. As expected, the lusitropic effect of isoprenaline was significantly
      blunted in ssTnI hearts. However, the positive inotropic response to isoprenaline
      was also blunted in ssTnI hearts. This effect was especially prominent for
      ejection-phase indices in isolated auxotonically loaded ssTnI hearts whereas the
      positive inotropic response of isovolumic hearts or unloaded isolated myocytes
      was much less affected. Isoprenaline decreased left ventricular end-systolic
      volume in wild-type hearts (10.6 +/- 1.6 to 6.2 +/- 0.4 microl at a preload of 20
      cmH(2)O; P < 0.05) but not transgenic hearts (11.4 +/- 1.3 to 10.9 +/- 1.3
      microl; P= n.s.). Likewise, isoprenaline increased stroke work in control hearts
      (14.5 +/- 1.0 to 22.5 +/- 1.8 mmHg microl mg(-1); P < 0.05) but not transgenic
      hearts (15.4 +/- 1.3 to 18.3 +/- 1.2 mmHg microl mg(-1); P= n.s.). The end
      systolic pressure-volume relation was increased by isoprenaline to a greater
      extent in control than transgenic hearts. However, isoprenaline induced a similar
      rise in intracellular Ca(2+) transients in transgenic and non-transgenic
      cardiomyocytes. These results indicate that cTnI has a pivotal role in the
      positive inotropic response of the murine heart to beta-adrenergic stimulation,
      an effect that is highly dependent on loading conditions and is most evident in
      the auxotonically loaded ejecting heart.

PMID- 14966322
TI  - Electron localization functions obtained from X-ray constrained Hartree-Fock
      wavefunctions for molecular crystals of ammonia, urea and alloxan.
AB  - Constrained Hartree-Fock wavefunctions in the superposition of isolated molecules
      model have been calculated from precise X-ray diffraction data on crystals of
      ammonia (NH(3)), urea [CO(NH(2))(2)] and alloxan [(CO)(4)(NH)(2)]. The X-ray
      constrained wavefunctions have been used to derive and examine 'electron
      localization' information, quantified by the true and approximate electron
      localization function (ELF), and the true and approximate Fermi hole mobility
      function (FHMF). The plots of the Fermi hole mobility function are the first to
      appear in the literature. The results are compared with corresponding isolated
      molecule Hartree-Fock calculations to gauge the effect of the crystal environment
      on the isolated molecules. An error analysis is performed to indicate the
      features in the plots which are well determined from the experimental data. The
      results from all plots are broadly consistent, but the approximate ELF shows some
      artifacts relative to the true ELF.

PMID- 14966321
TI  - Spectral momentum densities in matter determined by electron scattering.
AB  - In electron momentum spectroscopy (EMS), an incoming energetic electron (50 keV
      in this work) ionizes the target and the scattered and ejected electrons are
      detected in coincidence (at energies near 25 keV). From the energy and momentum
      of the detected particles, the energy omega and momentum q transferred to the
      target can be inferred. The observed intensity distribution I(omega, q) is
      proportional to the spectral momentum density of the target and hence provides a
      direct challenge to many-body theoretical descriptions of condensed matter. This
      is illustrated by comparing some many-body calculations with EMS measurements on
      graphite and polycrystalline aluminium.

PMID- 14966323
TI  - Time-dependent Takagi-Taupin eikonal theory of X-ray diffraction in rapidly
      changing crystal structures.
AB  - The Takagi-Taupin theory is extended by synthesizing it with the eikonal theory
      in a unified space-time approach based upon microscopic electromagnetism. The
      principal goal is the description of X-ray diffraction in a crystal undergoing
      subpicosecond and few-femtosecond changes.

PMID- 14966324
TI  - Ab initio structure solution by charge flipping.
AB  - In this paper, an extremely simple structure solution method termed charge
      flipping is presented. It works ab initio on high-resolution X-ray diffraction
      data in the manner of Fourier recycling. The real-space modification simply
      changes the sign of charge density below a threshold, while in reciprocal space
      the moduli F(obs) are retained resulting in an F(obs) map without weighting. The
      algorithm is tested using synthetic data for a wide range of structures, the
      solution statistics are analysed and the quality of reconstruction is checked.
      Finally, mathematical aspects of the algorithm are considered in detail, and
      these show that in this chaotic iteration process the solution is a limit cycle
      and not a fixed point.

PMID- 14966325
TI  - A five-dimensional model of dodecagonal Ta-Te quasicrystals with fractal
      occupation domains.
AB  - The consideration of two approximants of the first stable dodecagonal Ta-Te
      quasicrystal shows that the five-dimensional (5D) space group of the dodecagonal
      phase is P12m2(12(5)mm) and the structure consists of five layers within a 10 A
      period. A 5D quasicrystal model leading to the two approximate structures by the
      introduction of appropriate linear phason strains is derived by the section
      method. The model shows 20 A dodecagonal clusters (DDC) arranged at each vertex
      of the square-triangle dodecagonal pattern and has fractal occupation domains,
      suggesting that the quasicrystal has either a deterministic or a random square
      triangle packing of the DDC.

PMID- 14966326
TI  - The crystallographic fast Fourier transform. IV. FFT-asymmetric units in the
      reciprocal space.
AB  - New algorithms have been outlined for efficient calculation of the fast Fourier
      transform of data revealing crystallographic symmetries in previous papers by
      Rowicka, Kudlicki & Otwinowski [Acta Cryst. (2002), A58, 574-579; Acta Cryst.
      (2003), A59, 172-182; Acta Cryst. (2003), A59, 183-192]. The present paper deals
      with three implementation-related issues, which have not been discussed before.
      First, the shape of the FFT-asymmetric unit in the reciprocal space is discussed
      in detail. Next, a method is presented of reducing symmetry in-place, without the
      need to allocate memory for intermediate results. Finally, there is a discussion
      on how the algorithm can be used for the inverse Fourier transform. The results
      are derived for the case of the one-step symmetry reduction [Rowicka, Kudlicki &
      Otwinowski (2003). Acta Cryst. A59, 172-182]. The algorithms are also an
      important step in the more complicated cases of centered lattices [Rowicka,
      Kudlicki & Otwinowski (2003). Acta Cryst. A59, 183-192] and space groups with non
      removable special positions, such as cubic groups [Rowicka, Kudlicki & Otwinowski
      (2004), in preparation]. In the present paper, as in our previous ones, complex
      to-complex FFTs only are dealt with. Modifications needed to adapt the results to
      data with Hermitian symmetry will be described in our forthcoming article
      [Kudlicki, Rowicka & Otwinowski (2004), in preparation].

PMID- 14966327
TI  - Statistical approach to the phase problem.
AB  - The minimal function and its minimal principle employed in the traditional Shake
      and-Bake algorithm rely on the probabilistic estimates of the cosines of the
      structure invariants. In this paper, a novel statistical approach to the phase
      problem, which utilizes statistical properties of the structure invariants, is
      proposed. The statistical maximal function and its maximal principle are
      formulated, and the corresponding statistical Shake-and-Bake algorithm and its
      associated statistical parameter-shift procedure are proposed and tested. The
      test results show that the statistical approach to the phase problem is a simple,
      reliable, less computationally intensive and more efficient procedure for phase
      determination in X-ray crystallography.

PMID- 14966328
TI  - Hexagonal and trigonal sphere packings. II. Bivariant lattice complexes.
AB  - All homogeneous sphere packings were derived which correspond to point
      configurations of the 26 bivariant lattice complexes belonging to the hexagonal
      crystal family. They may be assigned to 109 sphere-packing types. Among these,
      there is a type of sphere packing with contact number 10 that was not described
      before. For seven of the 109 types, the inherent symmetry of the sphere packings
      with minimal density is cubic. In addition, three types of interpenetrating
      sphere packings were found and one type of interpenetrating 6(3) sphere layers.
      Such an arrangement was unknown so far. Some frequently occurring structure types
      that can be related to sphere packings are described as examples.

PMID- 14966329
TI  - Magnetically ordered quasicrystals: enumeration of spin groups and calculation of
      magnetic selection rules.
AB  - Details are given of the theory of magnetic symmetry in quasicrystals, which has
      previously only been outlined. A practical formalism is developed for the
      enumeration of spin point groups and spin space groups, and for the calculation
      of selection rules for neutron scattering experiments. The formalism is
      demonstrated using the simple, yet non-trivial, example of magnetically ordered
      octagonal quasicrystals in two dimensions. In a companion paper [Even-Dar Mandel
      & Lifshitz (2004). Acta Cryst. A60, 179-194], complete results are provided for
      octagonal quasicrystals in three dimensions.

PMID- 14966330
TI  - Symmetry of magnetically ordered three-dimensional octagonal quasicrystals.
AB  - The theory of magnetic symmetry in quasicrystals, described in a companion paper
      [Lifshitz & Even-Dar Mandel (2004). Acta Cryst. A60, 167-178], is used to
      enumerate all three-dimensional octagonal spin point groups and spin-space-group
      types and calculate the resulting selection rules for neutron diffraction
      experiments.

PMID- 14966331
TI  - 'Exact' formulation for pi-polarization waves of dynamical X-ray diffraction.
AB  - Self-consistent formulae for treating the pi-polarization waves in two-beam X-ray
      diffraction from single crystals are refined within the Laue formalism. These
      formulae overcome the inverted Delta.D not equal 0 problem and avoid all the
      unnecessary approximations in previous dynamical theories. Therefore, they are as
      accurate as the formulae for sigma-polarization waves.

PMID- 14966332
TI  - Integral lattices.
AB  - Most of the sharp peaks, recently reported by Constant & Shlichta [Acta Cryst.
      (2003), A59, 281-282], in the frequency distribution of known tetrahedral and
      hexagonal-rhombohedral inorganic compounds apparently correspond to integral
      lattices. These are characterized by an integral metric tensor of their basis
      vectors (up to a unit-length factor). Integral lattices also occur in molecular
      forms of axial-symmetric biomacromolecules, as illustrated by a RNA quadruplex. A
      general tendency in nature to reduce the number of structural free parameters is
      conjectured.

PMID- 14966333
TI  - Molecular motor proteins of the kinesin superfamily proteins (KIFs): structure,
      cargo and disease.
AB  - Intracellular organelle transport is essential for morphogenesis and functioning
      of the cell. Kinesins and kinesin-related proteins make up a large superfamily of
      molecular motors that transport cargoes such as vesicles, organelles (e.g.
      mitochondria, peroxisomes, lysosomes), protein complexes (e.g. elements of the
      cytoskeleton, virus particles), and mRNAs in a microtubule- and ATP-dependent
      manner in neuronal and non-neuronal cells. Until now, more than 45 kinesin
      superfamily proteins (KIFs) have been identified in the mouse and human genomes.
      Elucidating the transport pathways mediated by kinesins, the identities of the
      cargoes moved, and the nature of the proteins that link kinesin motors to cargoes
      are areas of intense investigation. This review focuses on the structure, the
      binding partners of kinesins and kinesin-based human diseases.

PMID- 14966334
TI  - Increasing prevalence of vancomycin-resistant Enterococcus faecium, expanded
      spectrum cephalosporin-resistant Klebsiella pneumoniae, and imipenem-resistant
      Pseudomonas aeruginosa in Korea: KONSAR study in 2001.
AB  - The 5th year KONSAR surveillance in 2001 was based on routine test data at 30
      participating hospitals. It was of particular interest to find a trend in the
      resistances of enterococci to vancomycin, of Enterobacteriaceae to the 3rd
      generation cephalosporin and fluoroquinolone, and of Pseudomonas aeruginosa and
      acinetobacters to carbapenem. Resistance rates of Gram-positive cocci were: 70%
      of Staphylococcus aureus to oxacillin; 88% and 16% of Enterococcus faecium to
      ampicillin and vancomycin, respectively. Seventy-two percent of pneumococci were
      nonsusceptible to penicillin. The resistance rates of Enterobacteriaceae were:
      Escherichia coli, 28% to fluoroquinolone; Klebsiella pneumoniae, 27% to
      ceftazidime, and 20% to cefoxitin; and Enterobacter cloacae, > or =40% to
      cefotaxime and ceftazidime. The resistance rates of P. aeruginosa were 21% to
      ceftazidime, 17% to imipenem, and those of the acinetobacters were > or =61% to
      ceftazidime, aminoglycosides, fluoroquinolone and cotrimoxazole. Thirty-five
      percent of non-typhoidal salmonellae were ampicillin resistant, and 66% of
      Haemophilus influenzae were beta-lactamase producers. Notable changes over the
      1997-2001 period were: increases in vancomycin-resistant E. faecium, and amikacin
      and fluoroquinolone-resistant acinetobacters. With the increasing prevalence of
      resistant bacteria, nationwide surveillance has become more important for optimal
      patient management, for the control of nosocomial infection, and for the
      conservation of the newer antimicrobial agents.

PMID- 14966335
TI  - Epidemiology of Salmonella enterica serotype typhi infections in Korea for recent
      9 years: trends of antimicrobial resistance.
AB  - The aim of this study is to characterize the epidemiological features of typhoid
      fever, categorized as class 1 notifiable disease in Korea and to analyze the
      recent change of antimicrobial resistance of Salmonella enterica serotype Typhi
      isolated nationwide. We retrospectively analyzed the 1,692 culture-proven cases
      from 1992 to 2000, using the data of the Korean National Institute of Health. The
      overall incidence of culture-proven typhoid fever was 0.41 per 100,000
      population. It occurred all over the country, but the southeastern part of Korean
      peninsula had the higher incidence rate than other areas. There were several
      outbreaks suspected, of which two outbreaks were confirmed. The resistance rate
      against chloramphenicol showed mild increase, but the ampicillin,
      trimethoprim/sulfamethoxazole, kanamycin, or nalidixic acid resistance remained
      at the similar levels for the past 9 yr. There were 21 (1.3%) multidrug-resistant
      (MDR) strains isolated since 1992, and the number of those has increased. Two
      strains resistant to ciprofloxacin were first identified in Korea.

PMID- 14966336
TI  - Therapeutic efficacy of meropenem for treatment of experimental penicillin
      resistant pneumococcal meningitis.
AB  - With the widespread emergence of antimicrobial resistance, combination regimens
      of ceftriaxone and vancomycin (C+V) or ceftriaxone and rifampin (C+R) are
      recommended for empirical treatment of pneumococcal meningitis. To evaluate the
      therapeutic efficacy of meropenem (M), we compared various treatment regimens in
      a rabbit model of meningitis caused by penicillin-resistant Streptococcus
      pneumoniae (PRSP). Therapeutic efficacy was also evaluated by the final bacterial
      concentration in the cerebrospinal fluid (CSF) at 24 hr. Each group consisted of
      six rabbits. C+V cleared the CSF at 10 hr, but regrowth was noted in 3 rabbits at
      24 hr. Meropenem monotherapy resulted in sterilization at 10 hr, but regrowth was
      observed in all 6 rabbits at 24 hr. M+V also resulted in sterilization at 10 hr,
      but regrowth was observed in 2 rabbits at 24 hr. M+V was superior to the
      meropenem monotherapy at 24 hr (reduction of 4.8 vs. 1.8 log10 cfu/mL,
      respectively; p=0.003). The therapeutic efficacy of M+V was comparable to that of
      C+V (reduction of 4.8 vs. 4.0 log10 cfu/mL, respectively; p=0.054). The meropenem
      monotherapy may not be a suitable choice for PRSP meningitis, while combination
      of meropenem and vancomycin could be a possible alternative in the treatment of
      PRSP meningitis.

PMID- 14966337
TI  - The changes in the mortality rates of low birth weight infant and very low birth
      weight infant in Korea over the past 40 years.
AB  - Total 36 reports on the mortality rates (MRs) of low birth weight infants (LBWI)
      and very LBWI (VLBWI) in Korea from the 1967 through 2001 were analyzed. We
      compared the changes in the MR by 5 and 10-yr interval. The MRs observed by 5-yr
      intervals from the early 1960s through the 1990s have drastically decreased. The
      MRs of LBWI are as follows: 23.1% and 23.6% in the 1960s, 17.3% and 16.8% in the
      1970s, 14.1% and 14.4% in the 1980s, and 8.1% in the early 1990s. The MRs of
      VLBWI have also fallen and were reported as follows: 68.2% and 63.7% in the
      1960s, 55.8% and 57.6% in the 1970s, 56.2% and 48.1% in the 1980s, 33.5% and
      24.5% in the 1990s, and 11.7% in the early 2000s. In every 10-yr period, the MRs
      of LBWI have decreased from 23.4% in 1960, to 17.0% in 1970, to 14.2% in 1980,
      and to 8.1% in 1990. The MRs of VLBWI also have decreased from 66.2% in 1960, to
      56.7% in 1970, to 50.8% in 1980, to 32.9% in 1990, and to 11.7% in 2000. The MR
      of LBWI and VLBWI has gone down remarkably due to improvements in neonatology in
      Korea as shown above.

PMID- 14966338
TI  - The distribution of fetal nuchal translucency thickness in normal Korean fetuses.
AB  - The aim of present study was to establish normative data for the distribution of
      nuchal translucency (NT) thickness in normal Korean fetuses. The data were
      collected from pregnant women with singleton pregnancies in whom fetal ultrasound
      was performed and the fetal NT thickness was measured between 11 and 14 weeks of
      gestation. Among them, a total of 2,577 fetuses with a known normal outcome were
      included in this study. The distribution of multiple of median (MoM) values of
      the NT thickness with crown-rump length (CRL) in 10-mm intervals and the 95th
      percentile of MoM were calculated with the linear regression method. The present
      study showed that NT measurements increase with increasing CRL and a false
      positive rate increases with increasing gestational age. Therefore, a fixed cut
      off point through the first trimester was not appropriate and each NT measurement
      should be examined according to the gestational age. The present study offers
      normative data of the fetal NT thickness in a Korean population, which can be
      used as reference for screening chromosomal aberrations or other congenital
      abnormalities in the first trimester.

PMID- 14966339
TI  - Development of an animal experimental model for a bileaflet mechanical heart
      valve prosthesis.
AB  - The objective of this study was to develop a pre-clinical large animal model for
      the in vivo hemodynamic testing of prosthetic valves in the aortic position
      without the need for cardiopulmonary bypass. Ten male pigs were used. A composite
      valved conduit was constructed in the operating room by implanting a prosthetic
      valve between two separate pieces of vascular conduits, which bypassed the
      ascending aorta to the descending aorta. Prior to applying a side-biting clamp to
      the ascending aorta for proximal grafting to the aortic anastomosis, an aorta to
      femoral artery shunt was placed just proximally to this clamp. The heart rate,
      cardiac output, Vmax, transvalvular pressure gradient, effective orifice area and
      incremental dobutamine stress response were assessed. A dose-dependent increase
      with dobutamine was seen in terms of cardiac output, Vmax, and the peak
      transvalvular pressure gradient both in the native and in the prosthetic valve.
      However, the increment was much steeper in the prosthetic valve. No significant
      differences in cardiac output were noted between the native and the prosthetic
      valves. The described pre-clinical porcine model was found suitable for site
      specific in-vivo hemodynamic assessment of aortic valvular prosthesis without
      cardiopulmonary bypass.

PMID- 14966340
TI  - Effects of pH on vascular tone in rabbit basilar arteries.
AB  - Effects of pH on vascular tone and L-type Ca2+ channels were investigated using
      Mulvany myograph and voltage-clamp technique in rabbit basilar arteries. In
      rabbit basilar arteries, high K+ produced tonic contractions by 11+/-0.6 mN
      (mean+/-S.E.,n=19). When extracellular pH (pHo) was changed from control 7.4 to
      7.9 ([alkalosis]o), K+-induced contraction was increased to 128+/-2.1% of the
      control (n=13). However, K+-induced contraction was decreased to 73+/-1.3% of the
      control at pHo 6.8 ([acidosis] o, n=4). Histamine (10 microM) also produced tonic
      contraction by 11+/-0.6 mN (n=17), which was blocked by post-application of
      nicardipine (1 microM). [alkalosis]o and [acidosis]o increased or decreased
      histamine-induced contraction to 134+/-5.7% and 27+/-7.6% of the control (n=4,
      6). Since high K+- and histamine-induced tonic contractions were affected by
      nicardipine and pHo, the effect of pHo on voltage-dependent L-type Ca2+ channel
      (VDCCL) was studied. VDCCL was modulated by pHo: the peak value of Ca2+ channel
      current (IBa) at a holding of 0 mV decreased in [acidosis]o by 41+/-8.8%, whereas
      that increased in [alkalosis]o by 35+/-2.1% (n=3). These results suggested that
      the external pH regulates vascular tone partly via the modulation of VDCC in
      rabbit basilar arteries.

PMID- 14966341
TI  - Serum ethanol levels after alcohol sclerotherapy of arteriovenous malformations.
AB  - We analyzed the effects of several factors on the serum ethanol levels after
      alcohol sclerotherapy in the arteriovenous malformations (AVMs) retrospectively.
      Blood ethanol level, amounts of given alcohol, location of lesions, methods of
      flow control, and Doppler resistive index (RI) were analyzed. The results of
      linear regression analysis showed that the amount of alcohol administered was the
      predictor of serum ethanol level (r2=0.75, p<0.001). The average amount of
      injected alcohol was 0.89 mL/kg in the patients with the serum levels above the
      legal intoxication level (>80 mg/dL). Location of the lesions was not related
      with the serum ethanol level (p=0.643), and other variables such as forms of flow
      control and RI were not related to the serum ethanol level after controlling for
      injected amounts of alcohol (analysis of covariance). It is recommended to keep
      an eye on the possibility of intoxication when using the amounts of alcohol
      exceeding 0.89 mL/kg in the sclerotherapy of AVMs.

PMID- 14966342
TI  - Effects of propofol on endotoxin-induced acute lung injury in rabbit.
AB  - This study was undertaken to clarify the effects of propofol on endotoxin-induced
      acute lung injury. Rabbits were randomly assigned to one of four groups. Each
      group received intravenous infusion of saline only, saline and Escherichia coli
      endotoxin, propofol (1 mg/kg bolus, then 5 mg/kg/hr) and endotoxin, or propofol
      (4 mg/kg bolus, then 20 mg/kg/hr) and endotoxin respectively. Infusion of saline
      or propofol was started 0.5 hr before the infusion of saline or endotoxin, and
      continued for 6 hr thereafter. The lungs of rabbits were ventilated with 40%
      oxygen. Mean blood pressure, heart rate, arterial oxygen tension (PaO2), and
      peripheral blood leukocyte and platelet count were recorded. The wet/dry (W/D)
      weight ratio of lung and lung injury score were measured, and analysis of
      bronchoalveolar lavage fluid (BALF) was done. Endotoxin decreased PaO2, and
      peripheral blood leukocyte and platelet count. And it increased W/D ratio of
      lung, lung injury score and leukocyte count, percentage of PMN cells,
      concentration of albumin, thromboxane B2 and IL-8 in BALF. Propofol attenuated
      all these changes except the leukocyte count in peripheral blood. In conclusion,
      propofol attenuated endotoxin-induced acute lung injury in rabbits mainly by
      inhibiting neutrophil and IL-8 responses, which may play a central role in sepsis
      related lung injury.

PMID- 14966343
TI  - Relationships between high-resolution computed tomography, lung function and
      bacteriology in stable bronchiectasis.
AB  - To determine the relationship between high-resolution computed tomography (HRCT)
      findings, lung function, and bacteriology in bronchiectasis, we conducted a
      retrospective study of 49 Korean patients with stable bronchiectasis. To quantify
      the extent and severity of bronchiectasis, we used a CT scoring system consisting
      of bronchial dilatation, bronchial wall thickening, the number of bronchiectatic
      segments, the number of bulla, and the number of emphysema segments. The presence
      of air-fluid levels and lung consolidation were also evaluated. The results of CT
      scoring, spirometry and sputum culture were analyzed. Patients with cystic
      bronchiectasis had higher CT score, more dilated lumen and lower forced vital
      capacity (FVC), forced expiratory volume in 1 sec (FEV1), and FEV1/FVC than
      patients with cylindrical bronchiectasis. Patients with mixed ventilatory
      impairment had larger number of bronchiectatic segments than patients with
      obstructive ventilatory impairment. CT score and the number of bronchiectatic
      segments were significantly associated with FVC and FEV1, while CT score and the
      number of emphysema segments were significantly associated with FEV1/FVC. Twenty
      one patients of 49 patients showed a positive sputum culture including 15 cases
      of Pseudomonas aeruginosa. The CT score was the most important predictor of lung
      function. The presence of air-fluid levels predicted bacterial colonization.

PMID- 14966344
TI  - Airway inflammation and allergen specific IgE production may persist longer than
      airway hyperresponsiveness in mice.
AB  - During the preclinical study of new therapeutic modality, we evaluate whether the
      treatment can reverse the established asthma phenotypes in animal model. However,
      few have reported on the long term persistence of asthma phenotypes upon re
      challenge with allergen (secondary challenge) in animal model. We evaluated the
      persistence of asthma phenotypes by secondary challenge at different times in
      previously challenged murine asthma model. BALB/c mice sensitized by
      intraperitoneal injections of 20 micro g of ovalbumin and 1 mg of alum on days 1
      and 14 were challenged initially by the inhalation of 1% ovalbumin for 30 min on
      days 21, 22, and 23. Each group of mice was rechallenged at 5, 7, 9, or 12 weeks
      after the initial challenge. Airway hyperresponsiveness, BAL fluid, airway
      histology and serum ovalbumin-specific IgE level were evaluated. Airway
      eosinophilia, airway inflammation and serum ovalbumin-specific IgE production
      persisted upon secondary allergen challenges at least 12 weeks after the initial
      challenge. However, airway hyperresponsiveness persisted only until mice were
      rechallenged 7 weeks after the initial challenge. Airway inflammation and
      allergen specific IgE production may persist longer than airway
      hyperresponsiveness in a mouse asthma model of secondary allergen challenge.

PMID- 14966345
TI  - Effect of cryoanalgesia combined with intravenous continuous analgesia in
      thoracotomy patients.
AB  - Fifty patients undergoing thoracotomy was studied to compare the effects of
      cryoanalgesia combined with intravenous continuous analgesia (IVCA). Patients
      were randomized into two groups: IVCA group and IVCA-cryo group. Subjective pain
      intensity was assessed on a visual analogue scale at rest (VAS-R) and during
      movement (VAS-M). Analgesic requirements were evaluated over the 7 days following
      surgery. Forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1)
      were measured before operation, on the 2nd and 7th postoperative days (POD). We
      interviewed patients by telephone to evaluate the prevalence of post-thoracotomy
      pain at the 1st, 3rd, and 6th months postoperatively. No significant differences
      were observed between the two groups with respect to postoperative pain,
      analgesic requirements, side effects, respiratory complications, or prevalence of
      post-thoracotomy pain. However, a significant increase in FVC and FEV1 was
      observed on the 7th POD in IVCAcryo group. The incidence of the post-thoracotomy
      pain at the 1st, 3rd, and 6th months postoperatively was 68, 60, and 44% in IVCA
      group, and 88, 68, and 28% in IVCAcryo group, respectively. Our study showed that
      cryoanalgesia combined with IVCA effectively restore respiratory function on 7th
      POD, but that it was not effective at reducing the incidence of post-thoracotomy
      pain.

PMID- 14966346
TI  - The outcomes of hypertransfusion in major ABO incompatible allogeneic stem sell
      transplantation.
AB  - Major ABO incompatibility may be potentially associated with immediate or delayed
      hemolysis and delayed onset of erythropoiesis in patients receiving allogeneic
      hematopoietic stem cell transplantation (HSCT). To determine if hemolysis can be
      prevented by the inhibition of graft erythropoiesis, we performed
      hypertransfusion and assessed red cell transfusion requirement and independence.
      Between October 1995 and December 2001, 28 consecutive patients receiving major
      ABO incompatible HSCT at Samsung Medical Center were hypertransfused to maintain
      their hemoglobin levels at 15 g/dL or more. We retrospectively compared the
      outcomes of these patients with those of 47 patients at Asan Medical Center whose
      target hemoglobin levels were 10 g/dL. Reticulocyte engraftment was significantly
      delayed in hypertransfused group (51 days vs. 23 days; p=.001). There was no
      significant difference in the total amount of red cells transfused within 90 days
      post-HSCT (25 units vs. 26 units; p=.631). No significant difference in the time
      to red cell transfusion independence was observed between the two groups (63 days
      vs. 56 days; p=.165). In conclusion, we failed to improve red cell transfusion
      requirement and independence in major ABO incompatible HSCT with
      hypertransfusion.

PMID- 14966347
TI  - Detection of aberrant p16INK4A methylation in sera of patients with liver
      cirrhosis and hepatocellular carcinoma.
AB  - Hepatocellular carcinomas (HCCs) show genomic alterations, including DNA
      rearrangements associated with HBV DNA integration, loss of heterozygosity, and
      chromosomal amplification. The genes most frequently involved are those encoding
      tumor suppressors. The p16INK4A tumor suppressor gene frequently displays genetic
      alteration in HCC tissues. The present study was performed to examine the
      incidence of methylated p16INK4A in the sera of liver cirrhosis (LC) and HCC
      patients, and to evaluate its role as a tumor marker of HCC. The sera of 23 LC
      patients and 46 HCC patients were examined in this study. The methylation status
      of p16INK4A was evaluated by methylation-specific PCR of serum samples.
      Methylated p16INK4A was detected in 17.4% (4/23) of LC patients and in 47.8%
      (22/46) of HCC patients. No association was demonstrated between p16INK4A
      methylation and serum AFP level. As the status of p16INK4A methylation was not
      associated with serum AFP level, it may have a role as a tumor marker of HCC.

PMID- 14966348
TI  - A prospective randomized study on two dose fractionation regimens of high-dose
      rate brachytherapy for carcinoma of the uterine cervix: comparison of efficacies
      and toxicities between two regimens.
AB  - To evaluate the toxicities and efficacies of two fractionation regimens of high
      dose-rate brachytherapy in uterine cervical cancer, patients were stratified by
      stage Ib-IIa versus IIb-IVa, and randomly assigned to receive 3 Gy fractions
      (group A) or 5 Gy fractions (group B). External radiotherapy was performed using
      a 10 MV radiography with a daily 1.8 Gy up to 30.6 Gy to the whole pelvis, and
      then with a midline shield up to 45.0 Gy. Brachytherapy was performed with 3 Gy x
      10 times or 5 Gy x 5 times, and this was followed by booster brachytherapy of a
      smaller fraction to the residual tumor. Between August 1999 to July 2000, 46
      patients were eligible. Median follow-up period was 42 months (5-49). The range
      of age was 37-83 yr (median, 58). The three-year disease-specific survival rates
      of group A (n=23) and B (n=23) were 90.5%, 84.9%, respectively (p=0.64). The
      three-year pelvic control rates of group A and B were 90.0% and 90.9%,
      respectively (p=0.92). The incidences of late complications of the rectum or
      bladder of grade 2 or greater in groups A and B were 23.8% and 9.1%, respectively
      (p=0.24). Our study showed that the results of two regimens were comparable.
      Fractionation regimen using 5 Gy fractions seems to be safe and effective, and
      offers shorter treatment duration.

PMID- 14966349
TI  - Methylglyoxal induces apoptosis mediated by reactive oxygen species in bovine
      retinal pericytes.
AB  - One of the histopathologic hallmarks of early diabetic retinopathy is the loss of
      pericytes. Evidences suggest that the pericyte loss in vivo is mediated by
      apoptosis. However, the underlying cause of pericyte apoptosis is not fully
      understood. This study investigated the influence of methylglyoxal (MGO), a
      reactive alpha-dicarbonyl compound of glucose metabolism, on apoptotic cell death
      in bovine retinal pericytes. Analysis of internucleosomal DNA fragmentation by
      ELISA showed that MGO (200 to 800 microM) induced apoptosis in a concentration
      dependent manner. Intracellular reactive oxygen species were generated earlier
      and the antioxidant, N-acetyl cysteine, inhibited the MGO-induced apoptosis. NF
      kappaB activation and increased caspase-3 activity were detected. Apoptosis was
      also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF-kappaB
      inhibitor, pyrrolidine dithiocarbamate. These data suggest that elevated MGO
      levels observed in diabetes may cause apoptosis in bovine retinal pericytes
      through an oxidative stress mechanism and suggests that the nuclear activation of
      NF-kappaB are involved in the apoptotic process.

PMID- 14966350
TI  - The relationship between disc degeneration and morphologic changes in the
      intervertebral foramen of the cervical spine: a cadaveric MRI and CT study.
AB  - A cadaveric study was performed to investigate the relationship between disc
      degeneration and morphological changes in the intervertebral foramen of cervical
      spine, including the effect on the nerve root. Seven fresh frozen human cadavers
      were dissected from C1 to T1, preserving the ligaments, capsules, intervertebral
      disc and the neural structures. The specimens were scanned with MRI and then
      scanned through CT scan in the upright position. Direct mid-sagittal and 45
      degree oblique images were obtained to measure the dimension of the
      intervertebral disc height, foraminal height, width, area and segmental angles.
      Disc degeneration was inversely correlated with disc height. There was a
      significant correlation between disc degeneration and foraminal width (p<0.005)
      and foraminal area (p< 0.05), but not with foraminal height. Disc height was
      correlated with foraminal width but not with height. The segmental angles were
      decreased more in advanced degenerated discs. There was a correlation between
      nerve root compression and decreased foraminal width and area (p<0.005). This
      information and critical dimensions of the intervertebral foramen for nerve root
      compression should help in the diagnosis of foraminal stenosis of the cervical
      spine in patients presenting with cervical spondylosis and radiculopathy.

PMID- 14966351
TI  - Bystander-mediated regression of murine neuroblastoma via retroviral transfer of
      the HSV-TK gene.
AB  - Selective introduction of genes conferring chemosensitivity into proliferating
      tumor cells may be used to treat cancer. We investigated the bystander effect of
      retrovirus-mediated gene transfer of herpes simplex virus thymidine kinase (HSV
      TK) gene to murine neuroblastoma cell line (neuro-2a) in vitro and in vivo, and
      we examined whether the mechanism of bystander effect in neuroblastoma would also
      depend on connexin-dependent gap junction and/or immune response. A strong
      bystander effect was observed in vitro, whereby nontransduced tumor cells in
      proximity to transduced cells acquired susceptibility to ganciclovir (GCV)
      killing. Implanted mixtures of wildtype cells and HSV-TK transduced cells showed
      a potent bystander effect upon administration of GCV in A/J mice. HSV-TK/GCV
      system in murine neuroblastoma induced systemic immunity. Immunohistochemical
      staining showed many CD4+ and CD8+ cell infiltration but did not show anti
      connexin 43+ cells. In conclusion, a strong bystander effect was observed in
      vitro and in vivo. The bystander effect in murine neuroblastoma might be
      dependent on immune response and/or on other mechanism such as protein
      phosphorylation or transfer of apoptotic vesicle, rather than connexin-dependent
      gap junction.

PMID- 14966352
TI  - Continuous brain-derived neurotrophic factor (BDNF) infusion after
      methylprednisolone treatment in severe spinal cord injury.
AB  - Although methylprednisolone (MP) is the standard of care in acute spinal cord
      injury (SCI), its functional outcome varies in clinical situation. Recent report
      demonstrated that MP depresses the expression of growth-promoting neurotrophic
      factors after acute SCI. The present study was designed to investigate whether
      continuous infusion of brain-derived neurotrophic factor (BDNF) after MP
      treatment promotes functional recovery in severe SCI. Contusion injury was
      produced at the T10 vertebral level of the spinal cord in adult rats. The rats
      received MP intravenously immediately after the injury and BDNF was infused
      intrathecally using an osmotic mini-pump for six weeks. Immunohistochemical
      methods were used to detect ED-1, Growth associated protein-43 (GAP-43),
      neurofilament (NF), and choline acethyl transferase (ChAT) levels. BDNF did not
      alter the effect of MP on hematogenous inflammatory cellular infiltration. MP
      treatment with BDNF infusion resulted in greater axonal survival and regeneration
      compared to MP treatment alone, as indicated by increases in NF and GAP-43 gene
      expression. Adjunctive BDNF infusion resulted in better locomotor test scores
      using the Basso-Beattie-Bresnahan (BBB) test. This study demonstrated that
      continuous infusion of BDNF after initial MP treatment improved functional
      recovery after severe spinal cord injury without dampening the acute effect of
      MP.

PMID- 14966353
TI  - X-linked severe combined immunodeficiency syndrome: the first Korean case with
      gamma c chain gene mutation and subsequent genetic counseling.
AB  - X-linked severe combined immunodeficiency (X-SCID) is a rare, life-threatening
      immune disorder, caused by mutations in the gamma c chain gene, which encodes an
      essential component of the cytokine receptors for interleukin-2 (IL-2), IL-4, IL
      7, IL-9, IL-15, and IL-21. A 13-month-old boy with recurrent infections who had
      reduced serum immunoglobulin levels and decreased numbers of CD3, CD16/56 cells
      was evaluated for gamma c chain gene mutation and protein expression. The patient
      had a C-to-T point mutation at nucleotide position 690, one of the hot spots,
      resulting in a single amino acid substitution of cysteine for arginine (R226C),
      as determined by direct sequencing and PCR-RFLP. The patient's mother was a
      heterozygous carrier. Percutaneous umbilical cord blood sampling was performed at
      the 6-month of gestation in a subsequent pregnancy. As the immunophenotype of the
      fetus showed an identical pattern, the pregnancy was terminated and genetic
      analysis of the abortus confirmed recurrence. This is the first report of the
      molecular diagnosis of X-SCID in Korea. Genetic analysis of the gamma c chain
      gene is useful for definite diagnosis and genetic counseling for X-SCID.

PMID- 14966354
TI  - Hemolytic anemia as a sequela of arsenic intoxication following long-term
      ingestion of traditional Chinese medicine.
AB  - We report on a 51-yr-old woman who developed intravascular hemolytic anemia
      caused by arsenic after long-term ingestion of a traditional Chinese medicine
      (TCM). Twelve years before the admission, she was diagnosed as
      neurocysticercosis. She has ingested a TCM for about 12 yr instead of undergoing
      medical therapy for the disease. She was presented with a severe Coombs'-negative
      hemolytic anemia with hemosiderinuria. The urine arsenic level was elevated
      suggesting the arsenic intoxication as a cause of the anemia. She was treated
      successfully with therapeutic red cell exchange without any sequelae.

PMID- 14966355
TI  - A case of Hodgkin's lymphoma associated with sensory neuropathy.
AB  - Peripheral neuropathies occur in lymphoma patients. Causes of neuropathy include
      chemotherapy, opportunistic infections, and the lymphoma itself. We report a
      patient with lymphoma whose chief complaint was a sensory loss in the hands and
      feet. Electrophysiologic studies and sural nerve biopsy showed sensory
      polyneuropathies. We hypothesize that this neuropathy is associated with lymphoma
      related ganglionopathy, and among the possible causes, we suspect that a systemic
      cause such as a paraneoplastic syndrome is the most likely pathogenic etiology.
      However, further follow-up will be necessary to see whether sensory symptoms
      change with lymphoma treatment.

PMID- 14966356
TI  - Appearance of systemic lupus erythematosus in patients with myasthenia gravis
      following thymectomy: two case reports.
AB  - We report two cases of systemic lupus erythematosus (SLE) in myasthenia gravis
      (MG) patients who had undergone thymectomy. SLE developed in the patients 3
      months or 13 yr after thymectomy, and polyarthritis was the main clinical
      manifestation of SLE. Both patients fulfilled at least four of the revised
      criteria for the classification of SLE. In this report, we describe two
      postthymectomy lupus patients and perform a comparative review of previous cases.

PMID- 14966357
TI  - Adult-onset Still's disease with disseminated intravascular coagulation and
      multiple organ dysfunctions dramatically treated with cyclosporine A.
AB  - Severe systemic manifestations of adult onset Still's disease (AOSD) are often
      fatal and occasionally related to hemophagocytic syndrome (HS). We describe the
      case of a 49-yr-old woman with AOSD presenting with non-remitting high fever,
      confusion, jaundice, hepatosplenomegaly, serositis, azotemia, pancytopenia,
      coagulopathy with disseminated intravascular coagulation (DIC),
      hyperferritinemia, acute acalculous cholecystitis and ileocolitis noted in
      computed tomographic images. The patient had a history of herpes zoster developed
      prior to the admission, but there is no history of diarrhea or abdominal pain.
      Although bone marrow examination was not performed due to hemorrhagic diathesis,
      we suspected AOSD-associated HS on the basis of clinical course without
      detectable infectious agents in cultures or serologic studies. Intravenous
      immunoglobulin, pulse methylprednisolone, oral cyclosporine A (CsA) and
      ceftriaxone brought about transient improvement of fever and confusion, but the
      disease progressed. After increasing CsA dose, all previously mentioned
      abnormalities disappeared rapidly. Accordingly, we believe that DIC and multiple
      organ dysfunctions might have been the complications of HS but not that of
      sepsis, and that CsA can be used as a first-line therapy in case of life
      threatening situations.

PMID- 14966358
TI  - Bronchial atresia associated with spontaneous pneumothorax: report of a case.
AB  - A 32-yr-old male patient with recurrent pneumothorax associated with bronchial
      atresia of the subsegmental branch of the posterior segmental bronchus of the
      right upper lobe was successfully treated with right upper lobectomy. Before
      surgery, the bronchial atresia with pneumothorax was suspected on the chest
      radiograph and CT scans, which showed the findings of bronchocele with localized
      hyperinflation of the right upper lobe. The examination of surgical specimen from
      the resected right upper lobe suggests that the cause of the recurrent
      pneumothorax was the rupture of the subpleural bullae in the hyperinflated lung
      segment distal to the atretic bronchus.

PMID- 14966359
TI  - Adenocarcinoma arising in gastric heterotopic pancreas: a case report.
AB  - A heterotopic pancreas in the gastrointestinal tract is mostly found incidentally
      and its malignant transformation is extremely rare. We describe the second case
      of adenocarcinoma arising in a gastric heterotopic pancreas of an asymptomatic 35
      yr-old man in Korea. Esophagogastroduodenoscopy revealed a submucosal tumor with
      an irregular central umbilication in the gastric antrum. A wedge resection
      specimen demonstrated a submucosal oligolocular cystic mass (1.7 x 1.4 x 1.2 cm)
      with a solid portion. Microscopically, the cystic portion was composed of dilated
      pancreaticobiliary type ducts with adjacent small foci of periductal glandular
      structures. The adenocarcinoma components in the solid area infiltrated the
      proper muscle and the overlying mucosa of the stomach. The transitional area
      between the benign ductal structures and the adenocarcinoma component was found.
      The follow-up course was uneventful 5 months postoperatively.

PMID- 14966360
TI  - Invasive cystic hypersecretory carcinoma of the breast: a case report.
AB  - Cystic hypersecretory lesions of the breast are rare. These breast lesions
      include cystic hypersecretory hyperplasia (CHH), atypical CHH, and cystic
      hypersecretory carcinoma (CHC). The characteristic features are dilated ducts and
      cysts filled with thyroid colloid-like eosinophilic secretion. Only seven cases
      of invasive CHC have been reported in the literature. Here, we report an
      additional case of invasive CHC. The histologic features of the tumor showed both
      micropapillary intraductal carcinoma and focal high-grade invasive carcinoma in a
      background of CHH. This case suggests that cystic hypersecretory breast lesions
      encompass a spectrum of pathologic lesions including CHH, atypical CHH, CHC, and
      invasive CHC.

PMID- 14966361
TI  - Two cases of lichen planus pigmentosus presenting with a linear pattern.
AB  - We report two cases of lichen planus pigmentosus (LPP) that developed in a
      unilateral linear pattern. The patients presented with unilateral linear brown
      macules on the extremities. Skin biopsy showed orthokeratosis, basal hydropic
      degeneration with scarce lymphohistiocytic infiltrates, and numerous melanophages
      in both patients. These patients, to the best of our knowledge, are the first
      cases of LPP presenting with a linear pattern. LPP should be considered in the
      differential diagnosis of linear hyperpigmented skin lesions.

PMID- 14966362
TI  - Glial choristoma in the middle ear and mastoid bone: a case report.
AB  - Heterotopic brain tissue usually involves extracranial midline structures of the
      head and neck such as nose, nasopharynx, and oral cavity. Its occurrence in the
      non-midline structures, including middle ear, is rare. We described a 50-yr-old
      man with heterotopic glial tissue in the middle ear and mastoid bone. The patient
      presented with progressive hearing loss for 8 yr. There was no history of
      congenital anomalies, trauma, or ear surgery. Computed tomography revealed a mass
      like lesion with soft tissue density occupying the middle ear cavity and mastoid
      antrum. At the operation, a gray-white fibrotic mass was detected in the
      epitympanic area. Mesotympanum and ossicles were intact. The patient underwent
      left simple mastoidectomy with type I tympanoplasty. During operation, definite
      cranial bone defect or cerebrospinal fluid leakage was not found. Histologically,
      the lesion was composed of exclusively mature, disorganized glial tissue with
      fibrovascular elements in a rather loose fibrillary background. Glial tissue
      showed diffuse positive reaction for glial fibrillar acidic protein and S100
      protein on immunohistochemical study.

PMID- 14966363
TI  - Immunology. Antigen-presenting cells in the gut.
AB  - It has been known for the past 85 years that mucosal responses can be stimulated
      by local presentation of antigen and that the gut immune system is capable of
      mounting both primary and secondary responses to potentially harmful antigens
      while avoiding the expression of damaging responses to harmless dietary proteins.
      How these types of responses are induced and regulated remains unclear. In the
      gut attention has for some time been focused on Peyer's patches (PP) due to
      evidence that they play a vital role in the induction of humoral and cellular
      responses. Moreover, it has been established that MHC class II molecules are
      found in the gut mucosa on a variety of cell types outside PP, namely the lamina
      propria (LP). Fed antigens have also been detected in the LP and studies have
      shown that LP cells can stimulate allogeneic mixed lymphocyte responses and are
      capable of presenting soluble protein antigen to naive T cells. This article
      reviews the present understanding of the possible roles of PP and LP in
      intestinal immunity in terms of induction, regulation, surveillance of immune
      responses and the antigen presenting cell types involved.

PMID- 14966364
TI  - Attenuation of mouse mesangial cell contractility by high glucose and mannitol:
      involvement of protein kinase C and focal adhesion kinase.
AB  - Hyperglycemia and mannitol activate protein kinase C (PKC) and induce mesangial
      cell hypocontractility that subsequently may modulate renal function. Since focal
      adhesion kinase (FAK) activation is known to be linked with PKC activity, FAK may
      also be involved in mesangial cell contraction. To facilitate our understanding
      of the PKC- and FAK-modulating mechanism, we developed an in vitro model of mouse
      mesangial cell hypocontractility induced by hyperglycemia or mannitol. Mouse
      mesangial cells (CRL-1927) were exposed to: normal D-glucose (group N), high D
      glucose (group H), and control groups at the same osmolality as H plus L-glucose
      (group L) and mannitol (group M). Changes in the planar surface area of cells in
      response to 1 microM phorbol 12-myristate 13-acetate (PMA) were determined.
      Western blot analyses for PKC, phosphorylated (p)-PKC, tyrosine phosphorylation,
      FAK, and p-FAK were done on each of these four groups. The effects of mannitol in
      various doses on cell contraction and activation of PKC and FAK were also
      assayed. The planar surface areas of groups H and M both showed an attenuated
      change in response to PMA stimulation. Before PMA stimulation, the baseline PKC
      expression of groups H and M showed a higher expression of p-PKC alpha and delta
      than that seen in group N (p < 0.05). Results of tyrosine phosphorylation and
      immunoprecipitation showed that FAK may be involved in this contraction process.
      The total amount of FAK showed no significant difference among the four
      experimental groups; however, p-FAK was found to have significantly increased in
      group M (p < 0.05). The use of PKC and tyrosine kinase inhibitors reduced PMA
      induced mesangial cell contraction in all four groups. Activation of PKC alpha,
      delta, and FAK with the resultant inhibition of mesangial cell contraction by
      mannitol was found to be dose-dependent. These results may provide a correlation
      between increased expression of several PKC isoforms and, in particular,
      increased phosphorylation levels of PKC alpha and delta and hypocontractility
      induced by high glucose and mannitol treatment. Furthermore, the mannitol-induced
      hypocontractility involving PKC and FAK occurred in a dose-dependent manner.

PMID- 14966365
TI  - N-acetylcysteine ameliorates lipopolysaccharide-induced organ damage in conscious
      rats.
AB  - Lipopolysaccharide is strongly associated with septic shock, leading to multiple
      organ failure. It can activate monocytes and macrophages to release
      proinflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1 beta (IL-1 beta), and nitric oxide (NO). The present experiments
      were designed to induce endotoxin shock by an intravenous injection of Klebsiella
      pneumoniae lipopolysaccharide (LPS, 10 mg/kg) in conscious rats. Arterial
      pressure and heart rate (HR) were continuously monitored for 48 h after LPS
      administration. N-Acetylcysteine was used to study its effects on organ damage.
      Biochemical substances were measured to reflect organ functions. Biochemical
      factors included blood urea nitrogen (BUN), creatinine (Cre), lactic
      dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT),
      alanine transferase (GPT), TNF-alpha, IL-1 beta, methyl guanidine (MG), and
      nitrites/nitrates. LPS caused significant increases in blood BUN, Cre, LDH, CPK,
      GOT, GPT, TNF-alpha, IL-1 beta, MG levels, and HR, as well as a decrease in mean
      arterial pressure and an elevation of nitrites/nitrates. N-Acetylcysteine
      suppressed the release of TNF-alpha, IL-1 beta, and MG, but enhanced NO
      production. These actions ameliorate LPS-induced organ damage in conscious rats.
      The beneficial effects may suggest a potential chemopreventive effect of this
      compound in sepsis prevention and treatment.

PMID- 14966366
TI  - Enhanced expression of angiopoietin-2 and the Tie2 receptor but not angiopoietin
      1 or the Tie1 receptor in a rat model of myocardial infarction.
AB  - Modulation of Tie2 receptor activity by angiopoietin ligands is crucial for
      angiogenesis, blood vessel maturation, and vascular endothelium integrity. The
      role of the angiopoietin (Ang) and Tie system in myocardial infarction is not
      well understood. To investigate the participation of the Ang/Tie in myocardial
      infarction, adult Sprague-Dawley rats with ligation of the left anterior
      descending coronary artery to induce myocardial infarction were studied. Ang1,
      Ang2, Tie1, and Tie2 were measured immediately after ligation of the coronary
      artery, and at 6 h, 1 and 3 days, and 1, 2, 3 and 4 weeks after ligation by
      Northern blotting, Western blotting, and immunohistochemical staining. Ang2 mRNA
      significantly increased from 2 weeks (2.1-fold) to 4 weeks (2.9-fold) after the
      infarction in the left ventricular free wall. Tie2 mRNA increased significantly
      from 1 week (2.1-fold) to 4 weeks (3.8-fold) after the infarction. Ang2 protein
      also significantly increased from 3 days (1.9-fold) to 4 weeks (3-fold) after the
      infarction in the left ventricular free wall. Tie2 protein increased 2.4-fold at
      3 weeks and 2.8-fold at 4 weeks after the infarction. Neither Ang1 nor Tie1 mRNA
      or protein showed any significant change at any time point after the infarction.
      The ratio of Ang2/Ang1 mRNA and protein in the study group was higher than that
      in the control group. Ang2 and Tie2 expression in nonischemic myocardium showed
      no significant change. Immunohistochemical study also showed increased
      immunoreactivity of Ang2 and Tie2 at the infarct border. In conclusion, Ang2 and
      Tie2 expressions significantly increased both spatial and temporal patterns after
      myocardial infarction in the rat ventricular myocardium, while Ang1 and Tie1
      receptor expression did not.

PMID- 14966367
TI  - Short-term ascorbic acid deficiency induced oxidative stress in the retinas of
      young Guinea pigs.
AB  - We examined whether short-term ascorbic acid deficiency induces oxidative stress
      in the retinas of young guinea pigs. Four-week-old guinea pigs were given a
      scorbutic diet (20 g/animal/day) with and without adequate ascorbic acid (400
      mg/animal/day) in drinking water for 3 weeks. The serum concentrations of the
      reduced form of ascorbic acid and the oxidized form of ascorbic acid in the
      deficient group were 14.1 and 4.1%, respectively, of those in the adequate group.
      The retinal contents of the reduced form of ascorbic acid and the oxidized form
      of ascorbic acid in the deficient group were 6.4 and 27.3%, respectively, of
      those in the adequate group. The retinal content of thiobarbituric acid-reactive
      substances, an index of lipid peroxidation, was 1.9-fold higher in the deficient
      group than in the adequate group. Retinal reduced glutathione and vitamin E
      contents in the deficient group were 70.1 and 69.4%, respectively, of those in
      the adequate group. This ascorbic acid deficiency did not affect serum
      thiobarbituric acid-reactive substances and reduced glutathione concentrations
      but increased serum vitamin E concentration. These results indicate that short
      term ascorbic acid deficiency induces oxidative stress in the retinas of young
      guinea pigs without disrupting systemic antioxidant status.

PMID- 14966368
TI  - The central serotonergic system mediates the analgesic effect of
      electroacupuncture on ZUSANLI (ST36) acupoints.
AB  - Evidence in the past decade indicates that the mechanisms of anti-nociception of
      electroacupuncture (EAc) involve actions of neuropeptides (i.e., enkephalin and
      endorphin) and monoamines (i.e., serotonin and norepinephrine) in the central
      nervous system. Our present results using a subcutaneous injection of formalin to
      test pain sensation in mice provide further understanding of the involvement of
      serotonin in the actions of EAc-induced analgesia. Our observations show that (1)
      EAc at three different frequencies (2, 10 and 100 Hz) elicited an anti
      nociceptive effect as determined by behavioral observations of reduced hindpaw
      licking; (2) exogenously intracerebroventricular administration of 5
      hydroxytryptamine (5-HT) exhibited an analgesic effect, which partially mimicked
      the analgesic actions of EAc; (3) the anti-nociception of EAc at different
      frequencies was attenuated after reduced biosynthesis of serotonin by the
      administration of the tryptophan hydroxylase inhibitor, P-chlorophenylalanine,
      and (4) the 5-HT(1A) and 5-HT(3) receptor antagonists, pindobind-5-HT(1A) and LY
      278584, respectively, blocked three different frequencies of EAc-induced
      analgesic effects, but the anti-nociceptive effect of 100 Hz EAc was potentiated
      by the 5-HT(2) receptor antagonist, ketanserin. These observations suggest that 5
      HT(1A) and 5-HT(3) receptors partially mediate the analgesic effects of EAc, but
      that the 5-HT(2) receptor is conversely involved in the nociceptive response.

PMID- 14966369
TI  - Glossogyne tenuifolia acts to inhibit inflammatory mediator production in a
      macrophage cell line by downregulating LPS-induced NF-kappa B.
AB  - Glossogyne tenuifolia (hsiang-ju) (GT) is a traditional antipyretic herb used in
      Chinese medicine; however, no information is available to explain its action. The
      objective of this research was to elucidate the molecular pharmacological
      activity and the effective components in the ethanol extract of GT. We found that
      GT had potent anti-inflammatory effects on the lipopolysaccharide (LPS)-activated
      murine macrophages, RAW264.7. GT downregulated LPS-induced expression of
      inducible nitric oxide synthase (iNOS) by blocking its transcription. GT also
      caused a dose-dependent inhibition of the release of prostaglandin E(2) by
      repressing the promoter activity of the inducible cyclooxygenase (COX-2) gene.
      Moreover, GT exerted a dose-dependent inhibition of the LPS-stimulated release of
      the proinflammatory cytokines, TNF-alpha, IL-1 beta, IL-6, and IL-12. To
      determine the mechanism by which GT inhibits LPS signaling, we focused on nuclear
      factor-kappa B (NF-kappa B) activation. Western blot analysis revealed that GT
      abolished LPS-induced inhibitor-kappa B phosphorylation. The electrophoretic
      mobility shift assay demonstrated that GT abolished LPS-mediated kappa B DNA
      binding activity. Moreover, macrophages were transfected with a vector coding for
      the luciferase reporter gene under the control of NF-kappa B cis-acting elements,
      and the transfected macrophages showed that the LPS-stimulated luciferase
      activity was GT-sensitive. These results suggest that GT attenuates inflammatory
      mediator synthesis of activated macrophages through an NF-kappa B-dependent
      pathway. The active components of GT were identified as oleanolic acid and
      luteolin-7-glucoside. Both of these compounds inhibited LPS-stimulated
      inflammatory mediator production and NF-kappa B activation. We conclude that GT
      inhibits NF-kappa B-mediated gene expression and downregulates inflammatory
      mediator production in murine macrophages.

PMID- 14966370
TI  - DHEA attenuates catecholamine secretion from bovine adrenal chromaffin cells.
AB  - Dehydroepiandrosterone (DHEA) is a putative anti-stress agent and stress is
      associated with the secretion of catecholamine from the adrenal gland, but the
      effects of DHEA on catecholamine secretion are not fully understood. Using bovine
      chromaffin cells, we found that DHEA inhibited catecholamine secretion and
      cytosolic Ca(2+) ([Ca(2+)](i)) rise coupled with nicotinic acetylcholine receptor
      (nAChR) without exerting an effect on (3)H-nicotine binding. In the case of high
      K(+) stimulation, DHEA effectively suppressed secretion without affecting
      [Ca(2+)](i) rise. Trifluoperazine (TFP), a calmodulin inhibitor, was capable of
      counteracting the inhibition of DHEA on high K(+)-induced secretions. In
      permeabilized cells, DHEA suppressed the Ca(2+)-induced secretion. These results
      suggest that DHEA (a) acts as a channel blocker that suppresses Ca(2+) influx and
      subsequent secretions associated with nAChR, or (b) affects the intracellular
      secretion machinery to suppress high K(+)-induced secretions without affecting
      the high K(+)-induced [Ca(2+)](i) rise.

PMID- 14966371
TI  - Thapsigargin and EGTA inhibit endothelin-1-induced glucose transport.
AB  - We have previously demonstrated that ET-1 may enhance glucose transport in 3T3-L1
      adipocytes, secondarily to its stimulatory effect on GLUT1 gene expression by a
      mitogen-activated protein kinase (MAPK)-dependent pathway. In the present study,
      we further tested the involvement of Ca(2+) in glucose uptake in response to ET
      1. Among a variety of Ca(2+)-related agents tested, EGTA and thapsigargin were
      found to suppress both the glucose uptake and intracellular Ca(2+) mobilization
      induced by ET-1, as determined by Fura-2 analysis. However, a phospholipase C
      inhibitor, U73122, also eliminated the intracellular calcium mobilization induced
      by ET-1, but had no effect on ET-1-stimulated glucose uptake. The finding that
      neither EGTA nor thapsigargin had any influence on ET-1-induced MAPK activation
      implies that some mechanism downstream of MAPK activation is involved. Further
      investigation showed that both agents exerted global inhibitory effects on
      protein and RNA syntheses. Since both thapsigargin and EGTA may deplete
      endoplasmic reticulum (ER) Ca(2+) stores, our results suggest that (1) ET-1
      induced glucose transport is independent of ET-1's effect on Ca(2+) mobilization
      and (2) depletion of ER Ca(2+) stores per se may interfere with ET-1's effect on
      GLUT1 expression.

PMID- 14966372
TI  - Cytoprotective response of A1, a Bcl-2 homologue expressed in mature human
      neutrophils and promyelocytic HL-60 cells, to oxidant stress-induced cell death.
AB  - The ability to generate reactive oxidative intermediates is one of the
      quintessential properties of mature human neutrophils. Endogenously generated
      oxidants have been shown to be an important mechanism underlying neutrophil cell
      death. In acute lung inflammation, newly recruited neutrophils further encounter
      external oxidants, including reactive oxygen and nitrogen intermediates. In our
      present study, we showed that A1, a constitutive and inducible Bcl-2 homologue
      expressed in mature circulating human neutrophils, might confer the protection
      from hydrogen peroxide (H(2)O(2))- and peroxynitrite (ONOO)-induced cell death.
      Utilizing the myeloid precursor cell line, HL-60, we further examined the
      hypothesis that A1 was capable of conferring cytoprotective activity against
      these oxidative stresses. Whereas the control-transfected HL-60 cells expressed
      small amounts of A1 and were sensitive to the biologically relevant, cell death
      inducing oxidants, H(2)O(2) and ONOO, the stable transfectants that overexpressed
      A1 were significantly more tolerant. Furthermore, there was a correlation between
      the level of A1 expression and the antiapoptotic activity. Thus, our results
      suggest a cytoprotective role of A1 in mature human neutrophils under oxidant
      stresses in host defense and inflammation.

PMID- 14966373
TI  - Curative potential of GM-CSF-secreting tumor cell vaccines on established
      orthotopic liver tumors: mechanisms for the superior antitumor activity of live
      tumor cell vaccines.
AB  - In preclinical studies, tumor cells genetically engineered to secrete cytokines,
      hereafter referred to as tumor cell vaccines, can often generate systemic
      antitumor immunity. This study investigated the therapeutic effects of live or
      irradiated tumor cell vaccines that secrete granulocyte-macrophage colony
      stimulating factor (GM-CSF) on established orthotopic liver tumors. Experimental
      results indicated that two doses (3 x 10(7) cells per dose) of irradiated tumor
      cell vaccines were therapeutically ineffective, whereas one dose (3 x 10(6)
      cells) of live tumor cell vaccines caused complete tumor regression. In vivo
      depletion of CD8+ T cells, but not natural killer cells, restored tumor formation
      in the live vaccine-treated animals. Additionally, the treatment of cells with
      live vaccine induced markedly higher levels of cytotoxic T lymphocyte activity
      than the irradiated vaccines in the draining lymph nodes. The higher levels of
      cytokine and antigen loads could partly explain the superior antitumor activity
      of live tumor cell vaccines, but other unidentified mechanisms could also play a
      role in the early T cell activation in the lymph nodes. A protocol using multiple
      and higher dosages of irradiated tumor cell vaccines also caused significant
      regression of liver tumors. These results suggest that the GM-CSF-secreting tumor
      cell vaccines are highly promising for orthotopic liver tumors if higher levels
      of immune responses are elicited during early tumor development.

PMID- 14966374
TI  - Mutations at KFRDI and VGK domains of enterovirus 71 3C protease affect its RNA
      binding and proteolytic activities.
AB  - The 3C protease (3C(pro)) of enterovirus 71 (EV71) is a good molecular target for
      drug discovery. Notably, this protease was found to possess RNA-binding activity.
      The regions responsible for RNA binding were classified as 'KFRDI' (positions 82
      86) and 'VGK' (positions 154-156) in 3C(pro) by mutagenesis study. Although the
      RNA-binding regions are structurally distinct from the catalytic site of EV71
      3C(pro), mutations in the RNA-binding regions influenced 3C(pro) proteolytic
      activity. In contrast, mutations at the catalytic site had almost no influence on
      RNA binding ability. We identified certain mutations within 3C(pro) which
      abrogated both the RNA-binding activity of the expressed, recombinant, protease
      and the ability to rescue virus from an infectious full-length clone of EV71
      (pEV71). Interestingly, mutation at position 84 from Arg(R) to Lys(K) was found
      to retain good RNA binding and proteolytic activity for the recombinant 3C(pro);
      however, no virus could be rescued when pEV71 with the R84K mutation was
      introduced into the infectious copy. Together, these results may provide useful
      information for using 3C(pro) as the molecular target to develop anti-EV71
      agents.

PMID- 14966375
TI  - Overexpression of Her-2/NEU in epithelial ovarian carcinoma induces vascular
      endothelial growth factor C by activating NF-kappa B: implications for malignant
      ascites formation and tumor lymphangiogenesis.
AB  - Vascular endothelial growth factor C (VEGF-C) is an important growth factor that
      governs lymphatic spread and the development of intraperitoneal tumors associated
      with epithelial ovarian cancer; however, its regulation is not yet understood.
      Overexpression of Her-2/NEU is related to poor survival in advanced epithelial
      ovarian carcinoma patients. Accordingly, this study attempted to analyze the
      association between the Her-2/NEU oncogene and VEGF-C in ovarian carcinoma and to
      elucidate the molecular mechanism of VEGF-C induction by Her-2/NEU.
      Immunohistochemistry was used to determine the expression of Her-2/NEU and VEGF-C
      in tissues from 41 patients with epithelial ovarian carcinoma. Several Her-2/NEU
      stably-transfected Caov-3 ovarian carcinoma cells were used to evaluate the
      effect of Her-2/NEU on VEGF-C, the possible regulation mechanism, and the
      biological function of VEGF-C. Our experimental results identified a significant
      association between the Her-2/NEU oncogene and VEGF-C expression in both
      epithelial ovarian cancer patients (p < 0.05; Fisher's exact test) and in vitro
      cell lines. The overexpression of Her-2/NEU in Caov-3 ovarian cancer cells
      resulted in induction of a considerable amount of VEGF-C mRNA and protein; this
      process was dose-dependently inhibited by herceptin. The generation of VEGF-C
      significantly increased endothelial permeability. Pharmacological and genetic
      inhibition assays revealed that the cytoplasmic signaling molecule, p38 MAPK, and
      the transcriptional factor, NF-kappa B, are critically involved in the
      transcriptional activation of the VEGF-C gene by Her-2/NEU. In conclusion, this
      work clearly establishes that the Her-2/NEU oncogene is essential for the
      regulation of VEGF-C in ovarian carcinoma. It may be possible to use the
      monoclonal antibody targeting Her-2/NEU receptor to limit the formation of
      malignant ascites and lymphatic spread in ovarian carcinoma.

PMID- 14966376
TI  - Genetic analysis of the APC gene in Taiwanese familial adenomatous polyposis.
AB  - Colorectal cancer has become the third leading cause of death from cancer in
      Taiwan. Familial adenomatous polyposis (FAP) is an autosomal dominant inherited
      disease characterized by the presence of multiple adenomatous polyps in the colon
      and rectum. The gene responsible for FAP (APC) was cloned in 1991. Extensive
      analyses of the mutation spectra in FAP kindreds have been performed in different
      countries, but the results have been highly variable (30-80%). In this study, we
      used denaturing high-performance liquid chromatography (DHPLC) followed by
      automatic sequencing in an effort to establish the mutation spectrum of APC from
      DNA of peripheral blood cells. Among the 6 FAP probands analyzed, mutations were
      detected in 3 (50%), 2 of which were novel. The first novel mutation was at codon
      2166, with a C to T transition, resulting in a stop codon. The second novel
      mutation was at codon 1971, with a C to G transversion, resulting in an amino
      acid change from serine to cysteine. The third mutation involved an A insertion
      in the sequence of -AAAAAA- at codons 1554-1556, which created a downstream stop
      codon (codon 1558). This study is the first to report mutation analysis in
      Taiwanese FAP probands.

PMID- 14966377
TI  - Influenza-B-virus-induced eye and brain malformations during early chick
      embryogenesis and localization of the viral RNA in specific areas.
AB  - Influenza is prevalent worldwide, and the teratogenic effects of influenza
      infection have been suspected to occur within the developing central nervous
      system. We herein report the sequelae of influenza B viral infection during early
      chick embryogenesis. Chick embryos at Hamburger-Hamilton stage 9 were infected by
      an in ovo injection under the blastoderm of influenza B virus (B/Taiwan/25/99).
      At 48 h after infection, gross malformations of the eye and brain, ranging from
      25 to 58% of 168 infected embryos, were observed, in contrast to 3-6% among 71
      mock-infected controls (p < 0.0001 for both eye and brain malformations).
      Histological analyses showed extensive tissue degeneration and aggregates of
      cells in the head mesenchyme, suggesting cell death and heterotopia. Influenza B
      viral RNA was directly localized by in situ hybridization with probes specific
      for the HA segment. Viral RNA was extensively detected in the head surface
      ectoderm and in the lung bud. In the developing brain, viral RNA was specifically
      located in the anterior neural retina, habenular area, mid-thalamus, and
      rhombencephalon. Our data show that influenza B virus can be a teratogenic agent
      in neural and nonneural embryonic tissues, raising concern for transplacental
      infection during early pregnancy.

PMID- 14966378
TI  - Nuclear hormone and orphan receptors: their role in neuronal differentiation and
      cytoprotection and in the pathogenesis of Parkinson's disease.
AB  - Human nuclear hormone receptors (NHR) and orphan receptors (NOR) act as
      transcription factors in response to a wide range of circulating hormones and
      unknown ligands. A role for NHR and NOR in disorders of the subcortical
      dopaminergic pathways such as Parkinson's disease (PD) is suggested by a wealth
      of recent data including experimental observations. Both classes of receptors
      promote the formation of specific neuronal identities, tissue patterning during
      embryonic development and the maturation of vulnerable monoaminergic and
      cholinergic neurons. NHR and NOR are also known to exert a neuroprotective
      function on adult neurons. The scope of this review is to revisit the functional
      profile of these receptors with particular reference to their activity in the
      development of selected neuronal populations relevant to the pathophysiology of
      PD and to discuss how they may relate to the neuropathological and clinical
      expression of the disease.

PMID- 14966379
TI  - Ionotropic glutamate receptor expression and dopaminergic modulation in the
      developing subthalamic nucleus of the rat: an immunohistochemical and
      electrophysiological analysis.
AB  - Using standard immunohistochemical procedures, we investigated the changes in the
      expression of ionotropic glutamate receptor (GluR) subunits, GluRl, GluR5/6/7,
      and NMDAR1, in the subthalamic nucleus of developing rats. The general sequence
      of development for each subunit was the same. At early postnatal ages, there was
      dense neuropil staining and cellular clustering which progressed to decreased
      neuropil staining and an even distribution of conspicuous cells in the later
      postnatal ages and in the adult. GluR5/6/7 displayed the earliest maturation,
      while GluR1 exhibited the slowest maturation. These morphological changes suggest
      a different time course for the functionality of GluR subtypes in the developing
      subthalamic nucleus. Correlative electrophysiological studies demonstrated
      functional GluRs as early as 16 days of age. All neurons tested displayed robust
      responses to kainate and N-methyl-D-aspartate, and these responses were modulated
      by dopamine.

PMID- 14966380
TI  - Can lateralizing sensorimotor deficits be identified after neonatal cerebral
      hypoxia-ischemia in rats?
AB  - The neonatal rat model of unilateral cerebral hypoxia-ischemia (HI) is commonly
      used to test the efficacy of therapeutic strategies for prevention or treatment
      of stroke in the immature brain. Traditionally neuroprotection has been defined
      as reduction in tissue injury; there is growing interest in complementary
      functional assessment. Our objectives were to determine whether lateralizing
      performance deficits could be detected in two sensorimotor tests not previously
      used after neonatal HI, and to determine whether performance reflected the extent
      of tissue damage. Seven-day-old rats that underwent right carotid ligation
      followed by 1.5 h in 8% O2 and age-matched controls were tested for sensorimotor
      performance on postnatal day 35 (P35). We evaluated initial forepaw placement on
      the wall of a cylinder, and time taken to contact and remove adhesive stickers
      from the dorsum of each forepaw. Cortical, striatal and hippocampal damage
      severity was evaluated on P36 by calculating the contralateral-ipsilateral
      percent difference in regional areas. There was an inverse relationship between
      cortical and striatal damage severity and percent contralateral forepaw
      initiation in the cylinder. There was a direct linear relationship between damage
      severity and the delay from contact to removal of the contralateral sticker.
      These two tests revealed quantifiable contralateral sensorimotor deficits 4 weeks
      after unilateral neonatal cerebral HI in animals with cortical and striatal
      damage.

PMID- 14966381
TI  - Expression of c-FOS in the brain after activation of L-type calcium channels.
AB  - In rodents, administration of the L-type calcium channel activators, +/-Bay K
      8644 and FPL 64176, causes an unusual neurobehavioral syndrome that includes
      dystonia and self-injurious biting. To determine the regional influence of these
      drugs in the brain, the induction of c-FOS was mapped after administration of
      these drugs to mice. In situ hybridization with an antisense riboprobe directed
      to c-FOS mRNA revealed widespread induction, with the highest levels in the
      striatum, cortex, hippocampus, locus coeruleus, and cerebellum. The induction of
      c-FOS mRNA was dose dependent, reached maximal expression approximately 60 min
      after drug treatment, and could be blocked by pretreatment with the L-type
      calcium channel antagonist, nifedipine. Immunohistochemical stains with an
      antibody directed to c-FOS protein revealed a pattern of induction similar to
      that obtained with in situ hybridization in most brain regions. These results
      demonstrate a very heterogeneous influence of L-type calcium channel activation
      in different brain regions, despite the nearly universal expression of these
      channels implied by more classical anatomical methods.

PMID- 14966382
TI  - Perinatal iron deficiency alters apical dendritic growth in hippocampal CA1
      pyramidal neurons.
AB  - Iron deficiency early in life is associated with cognitive disturbances that
      persist beyond the period of iron deficiency. Within cognitive processing
      circuitry, the hippocampus is particularly susceptible to insults during the
      perinatal period. During the hippocampal growth spurt, which is predominantly
      postnatal in rodents, iron transport proteins and their messenger RNA stabilizing
      proteins are upregulated, suggesting an increased demand for iron import during
      this developmental period. Rat pups deprived of iron during the perinatal period
      show a 30-40% decrease in hippocampal metabolic activity during postnatal
      hippocampal development. We hypothesized that this reduced hippocampal neuronal
      metabolism impedes developmental processes such as neurite outgrowth. The goals
      of the current study were to investigate the effects of perinatal iron deficiency
      on apical dendritic segment growth in the postnatal day (P) 15 hippocampus and to
      determine if structural abnormalities persist into adulthood (P65) following iron
      treatment. Qualitative and quantitative immunohistochemical analyses of dendritic
      structure and growth using microtubule-associated protein-2 as an index showed
      that iron-deficient P15 pups have truncated apical dendritic morphology in CA1
      and a persistence of an immature apical dendritic pattern at P65. These results
      demonstrate that perinatal iron deficiency disrupts developmental processes in
      the hippocampal subarea CA1 and that these changes persist despite iron
      repletion. These structural abnormalities may contribute to the learning and
      memory deficits that occur during and following early iron deficiency.

PMID- 14966383
TI  - Expression of creatine kinase isoenzyme genes during postnatal development of rat
      brain cerebrum: evidence for posttranscriptional regulation.
AB  - Brain creatine kinase (CKB) has a central role in the regeneration of ATP in the
      brain. During postnatal development of rat brain cerebrum, the CKB protein level
      was very low at postnatal day 1 and week 1 but by week 4 had increased 6- to 7
      fold and remained constant through week 10. Surprisingly, CKB mRNA levels were
      already maximal at postnatal day 1 and week 1, indicating that CKB protein
      expression does not simply reflect the levels of CKB mRNA and is likely regulated
      posttranscriptionally during early postnatal times. Interestingly, the majority
      of cytoplasmic CKB mRNA was found to be associated with polyribosomes both at
      postnatal day 3 and week 6. Therefore, low CKB protein levels at early postnatal
      times could either be due to (1) normal translation initiation of CKB mRNA
      followed by a subsequent arrest during elongation or termination and/or (2)
      normal translation of CKB mRNA followed by rapid degradation of CKB protein.
      However, CKB protein increased coincidently with ubiquitous mitochondrial CK
      protein, suggesting that a functional phosphocreatine energy shuttle is formed in
      the cerebrum during postnatal development. The apparent posttranscriptional
      regulation of CKB in early postnatal cerebrum contrasts with the transcriptional
      regulation controlling accumulation of CKB protein in postnatal developing
      cerebellum.

PMID- 14966384
TI  - Glucocorticoid-induced apoptosis in CNS microvascular pericytes.
AB  - Pericyte loss or migration from its vascular location may be an important step in
      microvascular remodeling. Decreased pericyte to endothelial ratios are
      characteristics of newly formed vessels as well as microvessels undergoing
      regression, and may be due to selective degeneration via necrotic cell death or
      via programmed cell death. In this study, we have examined glucocorticoid-induced
      apoptosis in primary rat CNS pericytes. Characterization of apoptosis was
      determined using five independent criteria: (1) the translocation of receptors
      for annexin V from the inner to the outer surface of the plasma membrane, (2) the
      translocation of cytochrome C from the mitochondria to the cytosol, (3) the
      induction of DNA fragmentation, (4) the induction of classic changes in cell
      morphology, and (5) the appearance of TUNEL-positive cells. Incubation of CNS
      pericytes with dexamethasone induced the appearance of apoptotic cells in a time-
      and dose-dependent manner. Pericytes express immunologically detectable
      glucocorticoid receptors, and addition of the glucocorticoid receptor antagonist
      mifepristone inhibited dexamethasone-induced pericyte apoptosis. That pericytes
      undergo apoptosis in response to dexamethasone suggests that the regulatory
      function of this steroid may be important in vascular development and that
      pericyte apoptotic cell death may accompany vascular regression. Deregulation of
      pericyte involvement in vascular homeostasis and hemostasis may result in
      clinical disease.

PMID- 14966385
TI  - From panhypopituitarism to combined pituitary deficiencies: do we need the
      anterior pituitary?

PMID- 14966386
TI  - Growth hormone and IGF-1.

PMID- 14966387
TI  - Genetics of diabetes.

PMID- 14966388
TI  - Genetics of endocrine and metabolic disorders: parathyroid.

PMID- 14966389
TI  - Genetics of the adrenal gland.

PMID- 14966390
TI  - Genetics of ovarian disorders: polycystic ovary syndrome.

PMID- 14966391
TI  - Genetic mechanisms that regulate testis determination.

PMID- 14966392
TI  - [Hepatitis viruses and development of hepatocellular carcinoma].
AB  - The incidence rate of hepatocellular carcinoma (HCC) has been increasing over the
      last 20 years. HCC is a worldwide, but the incidence is very high in countries of
      South East Asia, China, sub-Saharan Africa and southern Europe. Liver cirrhosis
      is the most important risk factor for the development of HCC, through necrotic
      proliferative and dysplastic activity. HBV is indicated as a carcinogen agent,
      while it is unknown the real role of HCV in hepatocarcinogenesis. The role played
      by aflatoxins, ethanol, hemochromatosis, familiarity and sex hormones is still
      undefined. The clinical presentation of HCC is similar to that of chronic
      hepatitis and cirrhosis indicating the need of a periodic screening (even 4-6
      months) with alpha-fetoprotein determination and abdominal ultrasound scan.
      Hepatic resection, liver transplantation and percutaneous ethanol injection are
      the options more frequently chosen for treating patients with HCC.

PMID- 14966393
TI  - [The choice of antibiotic therapy for bacterial infections in patients with
      cirrhosis of the liver].
AB  - Patients with liver cirrhosis have an impaired function of reticuloendothelial
      system; moreover they exhibit several defects of cellular and humoral immunity.
      These deficiencies enhance their susceptibility to bacterial infections. The
      prognosis is better if the infection is detected as early as possible and treated
      adequately. Except in cases of septicemia, empirical monotherapy is effective.
      Broad-spectrum beta-lactam antibiotics have proved efficient for the treatment of
      severe infections; a limitation of third-generation cephalosporins is their
      ineffectiveness against Enterococci; the acylureidopenicillins may be a good
      choice since they are active against Enterococci and most enteric, pulmonary and
      urinary pathogens, including Escherichia coli and Streptococcus pneumoniae which
      are the pathogens most frequently isolated from cirrhotic patients with severe
      infection. Similarly, the combination of a beta-lactamase inhibitor with a
      penicillin may offer an adequate antibacterial spectrum. Piperacillin, like other
      beta-lactam antibiotics, can induce leukopenia in patients with cirrhosis; the
      more severe the hepatic dysfunction, the greater the risk; a reduction in dosages
      is necessary. Meropenem monotherapy is effective and safe for the initial
      therapeutic regimen of bacterial infection. The fluoroquinolones may be useful
      for the treatment of infections in liver cirrhosis; however, the marginal
      activity against S. pneumoniae is a drawback. Oral long-term fluoroquinolone
      administration is utilized for the prevention of spontaneous bacterial
      peritonitis recurrence; selective intestinal decontamination with
      fluoroquinolones is useful in preventing bacterial infections in cirrhosis with
      gastrointestinal hemorrhage. Given the high risk of nephrotoxicity due to
      aminoglycosides in liver cirrhosis, these antibiotics should be used only in
      cases of severe infection with septicemia, in which beta-lactam-aminoglycoside
      combination is indicated for rapid bactericidal effect and enhanced killing
      afforded by synergism. Perhaps a short course (no more than 3 days) and a once
      daily schedule of administration would minimize the risk of aminoglycoside
      induced nephrotoxicity.

PMID- 14966394
TI  - [Haemophilus influenzae type b in meningitis: antibiotic resistance in pediatric
      patients].
AB  - A retrospective study on 357 children admitted to four Pediatric Infectious
      Disease Centers in Rome, affected by acute meningitis, during 10 years period,
      between January, 1, 1985 and December, 31, 1994 was carried out. Haemophilus
      influenzae type b was detected in 110 patients; all children aged between 1 month
      and 5 years; the maximum incidence (74.5%) was observed in patients under two
      years. The following diagnostic criteria were utilized: Gram stain of CSF; Latex
      test on CSF, blood, urine; CSF and blood cultures. The in vitro sensitivity of 65
      isolates was tested by using the Kirby-Bauer method. We detected 15.3% of strains
      resistant to Ampicillin and 1.5% resistant to CAF. We also observed a high number
      of Hib strains resistant to Erythromycin and Cotrimoxazole. Only one strain
      Ceftriaxone resistant was isolated, confirming the high in vitro sensibility Hib
      to III generation cephalosporins that still remain the first choice drugs in Hib
      meningitis.

PMID- 14966395
TI  - [Attitudes and knowledge towards condom use among adolescents and young adults in
      Southern Italy].
AB  - A correct and consistent condom use can minimize the risk of acquiring HIV
      infection through sexual intercourse. The aim of this study has been to assess
      knowledge and attitudes towards condom use among adolescents and young adults
      living in southern Italy. 620 randomly selected subjects have been interviewed by
      means of a 16-item standardized questionnaire: 87.3% consider condom an useful
      tool in the prevention of sexually transmitted diseases; however, 53.5% think
      that condom may reduce sexual pleasure and 26.8% state that its cost is too high
      to allow regular use. These results emphasize the need of carefully planned
      programs aimed to overcome objective and subjective barriers in the use of condom
      to prevent HIV infection spreading.

PMID- 14966396
TI  - [Serum anti-HIV IgA in seropositive patients and in subjects at risk of HIV
      infection].
AB  - To detect the presence of anti-HIV IgA in HIV infected subjects and in
      seronegative subjects at risk of infection, we assessed a Western Blot using
      nitrocellulose strips with HIV separated proteins. We tested at least 2 different
      serum samples from 9 anti-HIV positive subjects (Group A), 9 anti-HIV negative
      subjects at risk of infection (Group B) and 9 controls (Group C). One subject in
      Group B became anti-HIV positive during the observation. Anti-HIV IgA were
      detected in all patients of Group A, in 66.6% of patients of Group B and in no
      patient of Group C. The subject who seroconverted during the observation showed
      positivity for IgA anti-HIV in both serum samples, while anti-HIV IgG became
      detectable only on the second serum sample. A newborn from a seropositive mother
      showed maternal anti-HIV IgG on the first 2 out of 3 serum samples while showed
      anti-HIV IgA positivity on the third sample only. This child is still anti-HIV
      negative.

PMID- 14966397
TI  - [Polymerase chain reaction (PCR) for the detection of HIV proviral DNA (pDNA) in
      subjects at risk of infection].
AB  - To detect HlV proviral DNA in lymphocytes from subjects at risk of acquiring HIV
      infection, we assessed a Polymerase Chain Reaction Assay using the SK38 and SK39
      primers for the amplification and the SK19 probe for the hybridization. The
      detection of amplified HIV-DNA was obtained by a new colorimetric method, the DNA
      enzyme immunoassay (DEIA). The PCR we performed allowed to detect HIV-pDNA in
      lymphocytes of 13 out of 64 subjects at risk of acquiring HIV infection. Seven of
      these 13 became anti-HIV positive during a follow up of 8 months.

PMID- 14966398
TI  - [Otomastoiditis caused by Mycobacterium avium: a case report].
AB  - Non tuberculous Mycobacterial (NTM) Infections mainly affect immunocompromised
      patients, appearing as disseminated or pulmonary disease. In immunocompetent
      children the most common form of infection with NTM is cervical adenitis. Ear
      infection seems to be a rare disease. We present a case of otomastoiditis caused
      by Mycobacterium avium in a 15 months old child, immunologically normal. Patient
      was referred for persistent right otitis unresponsive to routine medical therapy.
      TC scan of the ear and temporal bones revealed: soft tissue in external auditory
      canal, Eustachian canal, and middle ear overlying ossicles with erosion of tegmen
      tympani. Tuberculin skin test was positive with 5 units PPD and culture yielded
      M. avium. The patient undergo timpanomastoidectomy and medical therapy with
      antituberculous drugs and Steroids, subsequently he was given Clarithromycin and
      Rifabutin. M. avium is an ubiquitous low grade pathogen found in soil, water,
      dust and food. There is no evidence of direct transmission. Only a few cases of
      otomastoiditis due to M. avium have previously been reported. The case presented
      underlines the importance of microbiological investigations. When a NTM infection
      is suspected surgeons and infectious diseases specialists should cooperate to
      find an optimal treatment regimen of this unusual disease.

PMID- 14966399
TI  - [A case report of Listeria monocytogenes infection in a patient with AIDS.
      Efficacy of treatment with cotrimoxazole associated with rHuG-CSF (filgrastim)].
AB  - Listeriosis is an emerging opportunistic infection in the immunocompromised host.
      A case of sepsis due to Listeria monocytogenes in a patient with advanced HIV
      infection and severe neutropenia, treated for an underlying non-Hodgkin's
      lymphoma, is described. Therapy with cotrimoxazole associated with rHuG-CSF
      (filgrastim) led to a rapidly favourable clinical and microbiological outcome,
      and to the correction of concurrent neutropenia. The case report is discussed
      according to a literature review of all cases of listeriosis reported until now
      in the setting of HIV infection and AIDS. In particular, the role of both
      cotrimoxazole and rHuG-CSF adjunct in the treatment of listeriosis in the
      immunocompromised patient is focused.

PMID- 14966400
TI  - Severe herpetic whitlow in an HIV-1 and HIV-2 infected patient.
AB  - Our paper describes an unusual case of herpetic whitlow due to HSV-2 in an HIV-1
      and HIV-2 infected patient. This patient was a 33-year-old cook, HIV-1Ab and HIV
      2Ab positive for 4 years. The CD4+ cell count was below 50 cells/microL and no
      previous AIDS-defining illness happened. After having had a jagged tearing wound
      by a carving-knife on index finger of his right hand, he showed a rapid advancing
      erosion, which completely encircled his forefinger, due to HSV-2. Twenty days
      later he also showed two small adjacent lesions on penile shaft which rapidly
      extended with multiple subpreputial lesions. These lesions were caused by HSV-2
      infection too. Both, finger and penile lesions, completely healed after a 3-week
      treatment with intravenous and oral acyclovir.

PMID- 14966402
TI  - [Syphilis and prostitution].

PMID- 14966401
TI  - [Bacterial Eradication Index (BEI): a new parameter to evaluate the efficacy of
      antibiotics in acute otitis].

PMID- 14966404
TI  - Facial transplantation: a working party report from the Royal College of Surgeons
      of England.

PMID- 14966405
TI  - Monitoring of NFAT-regulated gene expression in the peripheral blood of allograft
      recipients: a novel perspective toward individually optimized drug doses of
      cyclosporine A.
AB  - BACKGROUND: With the introduction of cyclosporine A (CsA), long-term allograft
      function has significantly improved. Problems related to limited therapeutic
      margins and CsA toxicity remain unsolved. Until now there have been no reliable,
      practical markers to measure the biologic activity of CsA in vivo. METHODS:
      Expression of NFAT (nuclear factor of activated T cells)-regulated genes
      (interleukin 2, interferon-gamma, and granulocyte-macrophage colony-stimulating
      factor) in phorbol myristate acetate/ionomycin-stimulated peripheral blood from
      healthy volunteers (n=34) and from stable renal (n=25), cardiac (n=26), and liver
      (n=14) transplant recipients receiving CsA therapy was measured by quantitative
      real-time reverse transcriptase-polymerase chain reaction before and 2 hr after
      drug intake. Gene expression and CsA plasma levels were correlated. RESULTS: Two
      hours after oral CsA ingestion, the mean suppression of induced interleukin 2,
      interferon-gamma, and granulocyte-macrophage colony-stimulating factor gene
      expression was 85%. The individual decline of NFAT-regulated gene expression and
      the total drug exposure at this time point were closely related. Six hours after
      oral CsA uptake, gene expression levels reached predose values and subsequently
      increased further in some patients (rebound effect). CONCLUSION: Quantitative
      measurement of the inhibition of NFAT-regulated gene expression 2 hr after CsA
      intake represents a novel approach to assess the biologic effectiveness of CsA
      therapy and has the potential to enable individualized immunosuppressive
      regimens.

PMID- 14966406
TI  - A different amyloid formation mechanism: de novo oculoleptomeningeal amyloid
      deposits after liver transplantation.
AB  - BACKGROUND: Liver transplantation has served as a treatment for patients with
      familial amyloidotic polyneuropathy (FAP) because variant transthyretin (TTR),
      the pathogenic protein of FAP, is predominantly produced by the liver. However,
      the effect on amyloid formation of TTR that is synthesised by the retina and the
      choroid plexus remains to be elucidated in FAP patients with liver transplants.
      OBJECTIVE: To investigate changes in ocular tissues and the central nervous
      system (CNS) of FAP patients after liver transplantation. DESIGN: Clinical study.
      SETTING: Graduate School of Medical Sciences, Kumamoto University, Japan.
      INTERVENTION: Transplantation of livers from cadaveric or living donors.
      MEASUREMENTS: Preoperative measures and postoperative (16-108 months) follow-up
      of clinical data, including routine ophthalmologic, neurologic, and laboratory
      evaluations. RESULTS: In 22 patients with FAP related to the amyloidogenic TTR
      (ATTR) Val30Met and 3 patients with FAP ATTR Tyr114Cys, after liver
      transplantation, 3 patients began to show evidence of de novo glaucoma, and 1 had
      vitreous opacity that was caused by the variant TTR. Another three patients
      showed new amyloid deposits in the pupillary margin, which could lead to glaucoma
      and vitreous opacity. As for changes in the CNS and levels of total protein and
      TTR in cerebrospinal fluid (CSF), after liver transplantation, two FAP ATTR
      Tyr114Cys patients exhibited de novo amyloid deposition in the leptomeninges, and
      total protein and TTR levels in CSF were significantly increased. CONCLUSIONS:
      Oculoleptomeningeal involvement in FAP was not prevented by liver transplantation
      because variant TTR produced by the retina and the choroid plexus forms amyloid
      fibrils in situ.

PMID- 14966407
TI  - Human plasma as a dermal scaffold for the generation of a completely autologous
      bioengineered skin.
AB  - BACKGROUND: Keratinocyte cultures have been used for the treatment of severe burn
      patients. Here, we describe a new cultured bioengineered skin based on (1)
      keratinocytes and fibroblasts obtained from a single skin biopsy and (2) a dermal
      matrix based on human plasma. A high expansion capacity achieved by keratinocytes
      grown on this plasma-based matrix is reported. In addition, the results of
      successful preclinical and clinical tests are presented. METHODS: Keratinocytes
      and fibroblasts were obtained by a double enzymatic digestion (trypsin and
      collagenase, respectively). In this setting, human fibroblasts are embedded in a
      clotted plasma-based matrix that serves as a three-dimensional scaffold. Human
      keratinocytes are seeded on the plasma-based scaffold to form the epidermal
      component of the skin construct. Regeneration performance of the plasma-based
      bioengineered skin was tested on immunodeficient mice as a preclinical approach.
      Finally, this skin equivalent was grafted on two severely burned patients.
      RESULTS: Keratinocytes seeded on the plasma-based scaffold grew to confluence,
      allowing a 1,000-fold cultured-area expansion after 24 to 26 days of culture.
      Experimental transplantation of human keratinocytes expanded on the engineered
      plasma scaffold yielded optimum epidermal architecture and phenotype, including
      the expression of structural intracellular proteins and basement-membrane
      components. In addition, we report here the successful engraftment and stable
      skin regeneration in two severely burned patients at 1 and 2 years follow-up.
      CONCLUSIONS: Our data demonstrate that this new dermal equivalent allows for (1)
      generation of large bioengineered skin surfaces, (2) restoration of both the
      epidermal and dermal skin compartments, and (3) functional epidermal stem-cell
      preservation.

PMID- 14966408
TI  - Optimization of bone tissue engineering in goats: a peroperative seeding method
      using cryopreserved cells and localized bone formation in calcium phosphate
      scaffolds.
AB  - BACKGROUND: Bone tissue engineering by combining cultured bone marrow stromal
      cells with a porous scaffold is a promising alternative for the autologous bone
      graft. Drawbacks of the technique include the delay necessary for cell culture
      and the complicated logistics. We investigated methods to bypass these drawbacks.
      Furthermore, we investigated the localization of bone formation inside the
      scaffold. METHODS: Bone marrow stromal cells from seven goats were culture
      expanded and cryopreserved. One week before surgery, some of the cells were
      thawed, cultured, and seeded on porous calcium phosphate scaffolds. The
      constructs were cultured for another week until implantation. The remaining
      cryopreserved cells were thawed just before implantation and peroperatively
      resuspended in plasma before combining with the scaffold. Scaffolds impregnated
      with fresh bone marrow, devitalized cultured constructs, and empty scaffolds
      served as controls. All samples were implanted in the back muscles of the goats
      for 9 weeks. RESULTS: Histologic examination showed minimal (<1%) bone in the
      empty and devitalized scaffolds, 4.2 +/- 5.1 bone area percent in the bone marrow
      samples, and significantly more bone in both the cultured and peroperatively
      seeded constructs (11.7 +/- 2.5 and 14.0 +/- 2.0%). The peripheral 350 microm of
      the implants contained significantly less bone. CONCLUSION: Peroperative
      preparation of osteogenic constructs with cryopreserved cells is feasible. These
      constructs yield substantially more bone than the scaffolds alone or scaffolds
      impregnated with fresh bone marrow. Bone deposition is much less on the scaffold
      periphery.

PMID- 14966409
TI  - Mouse-heart grafts expressing an incompatible carbohydrate antigen. II.
      Transition from accommodation to tolerance.
AB  - BACKGROUND: Immune response to incompatible ABO antigens on allografts may result
      in rejection, accommodation, or immune tolerance. Our objective has been to
      develop a model for studying these three types of immune response to incompatible
      carbohydrate antigen in alpha1,3-galactosyltransferase knockout (KO) mice. KO
      mice lack the alpha-gal epitope and can produce the anti-Gal antibody against it
      after immunization with pig kidney membranes (PKM) that express this epitope.
      METHODS: KO mice were transplanted with syngeneic wild-type (WT) heart expressing
      alpha-gal epitopes. Subsequently, the mice were lethally irradiated and received
      lymphocytes including memory anti-Gal B cells from PKM immunized KO mice. Immune
      response to incompatible alpha-gal epitopes on the graft was determined by
      transplanted-heart function and by production of anti-Gal after PKM
      immunizations. RESULTS: Anti-Gal B cells exposed for 1 to 2 weeks to alpha-gal
      epitopes of WT hearts differentiate into cells producing noncytolytic
      accommodating antibodies. Exposure for longer periods (2-4 weeks) induces a
      transition from accommodation into tolerance, indicated by the inability of mice
      to produce anti-Gal antibodies despite repeated PKM immunizations. WT hearts in
      accommodating and in tolerized mice continue to function for months. CONCLUSIONS:
      In the absence of T-cell help, anticarbohydrate B cells exposed to incompatible
      carbohydrate antigens of transplanted organs differentiate first into cells
      capable of producing accommodating antibodies, but, after prolonged exposure,
      these B cells gradually become tolerized. These findings suggest that prolonged T
      cell suppression in recipients of ABO-incompatible allografts may result in a
      similar induction of tolerance to incompatible blood-group antigens.

PMID- 14966410
TI  - Sustained spatial disturbance of bile canalicular networks during regeneration of
      the steatotic rat liver.
AB  - BACKGROUND: Although it is generally considered that livers with moderate
      steatosis can be safely used in the setting of living-donor liver
      transplantation, the effect of the regenerative process of such a graft on
      postoperative liver function is incompletely understood. We assessed the
      morphologic and functional alterations during the regeneration of fatty liver,
      with special reference to the biliary system. METHODS: Wistar rats with normal or
      fatty livers induced by a choline-deficient diet were subjected to 70% partial
      hepatectomy (PH). The regenerated liver weight and serum parameters were
      compared. Furthermore, to assess the spatial alterations of bile canalicular
      networks, the distribution of AGp110, a fibronectin receptor that localizes on
      the apical (bile canalicular) membrane of the hepatocytes, was analyzed
      immunohistochemically. RESULTS: The serum albumin levels of the fatty-liver rats
      decreased significantly after 24 hours, and this continued until day 7. The
      increase in the total bile acid levels of the fatty-liver group was higher and
      more prolonged compared with that of the normal-liver group. At 24 hours after
      PH, discontinuity of the AGp110-positive canalicular network was evident in both
      groups. At 7 days after PH, the typical AGp110-positive canalicular network was
      almost restored in the normal-liver group. In contrast, the fatty-liver group
      showed sustained discontinuity of canalicular networks at the same time point.
      CONCLUSIONS: The livers with moderate steatosis are associated with prolonged
      cholestasis after 70% PH, and this was caused, in part, by sustained spatial
      disturbance of bile canalicular networks during the regenerative process.

PMID- 14966411
TI  - Functional bioengineered corneal epithelial sheet grafts from corneal stem cells
      expanded ex vivo on a temperature-responsive cell culture surface.
AB  - BACKGROUND: Limbal stem-cell deficiency by ocular trauma or diseases causes
      corneal opacification and visual loss. Recent attempts have been made to
      fabricate corneal epithelial graft constructs, but the technology is still
      evolving. We have developed a novel cell-sheet manipulation technology using
      temperature-responsive culture surfaces to generate functional, cultivated
      corneal epithelial cell sheet grafts. METHODS: Human or rabbit limbal stem cells
      were cocultured with mitomycin C-treated 3T3 feeder layers on temperature
      responsive culture dishes at 37 degrees C. Cell sheets were harvested from the
      dishes after 2 weeks by reducing temperature to 20 degrees C. Histologic
      analyses, immunoblotting, and colony-forming assay were performed to characterize
      the cell sheets. Autologous transplantation was undertaken to reconstruct the
      corneal surfaces of rabbits with experimentally induced limbal stem cell
      deficiencies. RESULTS: Multilayered corneal epithelial sheets were harvested
      intact simply by reducing the temperature, without the use of proteases. Cell
      cell junctions and extracellular matrix on the basal side of the sheet, critical
      to sheet integrity and function, remained intact. A viable population of corneal
      progenitor cells, close in number to that originally seeded, was found in the
      sheets. Harvested sheets were easily manipulated, transplantable without any
      carriers, and readily adhesive to corneal stroma so that suturing was not
      required. Corneal surface reconstruction in rabbits was highly successful.
      CONCLUSIONS: Cell sheet engineering technology allows us to create intact,
      transplantable corneal epithelial cell sheets that retain stem cells from limbal
      stem cells expanded ex vivo. Our research indicates highly promising clinical
      capabilities for our bioengineered corneal epithelial sheet.

PMID- 14966412
TI  - Prolonged survival of rat islet xenografts in mice after CD45RB monotherapy.
AB  - BACKGROUND: Pancreatic islet transplantation can correct the disordered glucose
      metabolism of type 1 diabetes, but the number of successful transplants has been
      low because of the need for long-term immunosuppression and the limited
      availability of human islets. New approaches, such as the use of tolerance
      inducing treatment modalities and the use of islets of nonhuman sources, can
      possibly improve the success of islet transplantation. In the present study, the
      authors investigated the effect of anti-CD45RB treatment on the survival of islet
      xenografts. METHODS: Chemically induced diabetic mice underwent xenografting with
      rat islets and were treated with CD45RB antibodies on days -1, 0, and 5.
      Immunohistology and real-time polymerase chain reaction were used to study the
      effect of the treatment in the xenografts. The effect of anti-CD45RB treatment in
      peripheral blood of normal mice was measured with flow cytometry. RESULTS: In the
      treated mice, survival of the grafts was prolonged substantially. In the treated
      mice with functioning grafts, no lymphocytes were found infiltrating the
      transplanted islets on day 6; whereas in the untreated animals with functioning
      grafts, signs of rejection were evident. In the grafts of the treated animals,
      significantly less mRNA for interleukin (IL)-2, interferon-gamma, and IL-4 was
      found compared with the untreated mice. After CD45RB treatment, there was
      depletion or decrease of CD45RBbright cells from the peripheral blood.
      CONCLUSIONS: Our results show that a short course of anti-CD45RB monotherapy
      prolongs the survival of rat islet xenografts in C57BL/6 mice.

PMID- 14966413
TI  - Effect of FK506 on donor T-cell functions that are responsible for graft-versus
      host disease and graft-versus-leukemia effect.
AB  - BACKGROUND: FK506 is a potent immunosuppressive agent that is used in human graft
      versus-host disease (GvHD) prevention. However, the precise mechanisms for GvHD
      prevention and the effect on graft-versus-leukemia (GvL) activity are unknown.
      This study was undertaken to determine the effect of FK506, given at clinically
      relevant doses, on donor T-cell functions responsible for GvHD and GvL activity.
      METHODS: The effect of FK506 on GvHD prevention and GvL activity was investigated
      using a murine model of allogeneic bone-marrow transplantation in which mice were
      injected with a P815 leukemic cell line. The regulatory role of FK506 on donor T
      cells was tested by analysis of donor T-cell expansions in the spleen and donor
      anti-host T-cell proliferative and cytotoxic responses. mRNA expression of type 1
      T helper (Th1), Fas ligand (L), and granzyme B were also evaluated in target
      organs of GvHD. RESULTS: FK506 significantly prolonged the survival of GvHD mice
      when given at the trough level of 17.6 ng/mL, whereas it also blocked GvL effect
      in P815-injected GvHD mice. FK506 reduced the expansion of donor CD8+ and, to a
      lesser extent, CD4+ T cells in the spleen and inhibited donor anti-host T-cell
      proliferative and cytotoxic responses. It also inhibited the induction of Th1,
      FasL, and granzyme B mRNA expression in target organs of GvHD. CONCLUSIONS: FK506
      inhibits both GvHD and GvL activity when given at clinical doses by inhibiting
      donor T-cell expansion, donor anti-host T-cell reactivity, and Th1 immune
      responses.

PMID- 14966414
TI  - Community-acquired West Nile virus infection in solid-organ transplant
      recipients.
AB  - BACKGROUND: West Nile virus (WNV) is rapidly spreading through North America. In
      the general population, the majority of WNV infections are asymptomatic. During
      2002, an outbreak of WNV occurred in Toronto, Canada. We observed four cases of
      severe symptomatic community-acquired WNV infection in our organ-transplant
      population. METHODS: Patient data were obtained from chart review. WNV was
      diagnosed by acute and convalescent serology. Incidence was compared with data
      obtained from a population-based surveillance program. RESULTS: Four transplant
      patients had WNV encephalitis (n=3) or meningitis (n=1). Mean age was 44.5 (range
      26-58) years and transplant type included kidney (n=2), liver (n=1), and heart
      (n=1). The mean time posttransplant was 3.8 years (range 2 months-8 years). The
      presenting symptoms were fever (4/4), confusion (3/4), headache (4/4), and
      weakness (2/4). Cerebrospinal fluid showed a pleocytosis in all patients and
      elevated protein in three of four. All patients had identifiable occupational or
      recreational risk factors. There was no evidence that the infection was acquired
      by transfusion or the transplanted organ. Outcomes were full recovery (2/4),
      lower limb paralysis (1/4), and death (1/4). On the basis of active population
      surveillance data, the rate of WNV meningoencephalitis in the general population
      in the Toronto area was approximately 5 per 100,000. This compares to four cases
      in a transplant population of 2,000 patients (rate 200 per 100,000) (P<0.001).
      CONCLUSIONS: Transplant patients are likely at greater risk of severe neurologic
      disease caused by community-acquired WNV compared with the general population.
      Prevention of transmission and patient education may be more important in this
      population.

PMID- 14966415
TI  - Impact of recipient age on outcome of ABO-incompatible living-donor liver
      transplantation.
AB  - BACKGROUND: Transplantation of hepatic grafts from ABO-incompatible donors is
      controversial because of the risk of hyperacute rejection mediated by preformed
      anti-ABO antibodies. The aim of the present study was to evaluate the outcome of
      liver transplants performed with ABO-incompatible living-donor livers and to
      detect risk factors for development of complications. METHODS: From June 1990 to
      February 2000, 66 patients, 10 months to 55 years old (median, 2 years old),
      received 68 ABO-incompatible living-donor liver grafts. The antibody titer and
      clinical course were followed prospectively during a period ranging from 3 to 11
      years. RESULTS: The 5-year patient survival was 59%, 76%, and 80% for ABO
      incompatible, ABO-compatible, and ABO-identical grafts, respectively (P<0.01). In
      patients <1 year old, > or =1 to <8, > or =8 to <16, and and > or =16 years old,
      5-year survival was 76%, 68%, 53%, and 22%, respectively. The incidence of
      intrahepatic biliary complications and hepatic necrosis in ABO-incompatible
      living-related grafts (18% and 8%, respectively) was significantly (P<0.0001)
      greater than in ABO-compatible and ABO-identical grafts (both 0.6% and 0%,
      respectively). Predictive risk factors for increased mortality and morbidity were
      age greater than 1 year and elevated anti-ABO titers before transplantation.
      CONCLUSIONS: ABO-incompatible liver transplantation was carried out with relative
      safety in infants <1 year old but was not satisfactory in children >1 year in
      long-term follow-up. Patients aged >8 years remain at considerable risk of early
      fatal outcome because of hepatic necrosis, and new strategies to prevent antibody
      mediated rejection are required.

PMID- 14966416
TI  - A simple scoring system to evaluate the effects of cold ischemia on marginal
      liver donors.
AB  - BACKGROUND: Exactly what constitutes a marginal donor remains ill defined. The
      authors set out to create a scoring system that objectively classifies a donor as
      marginal or nonmarginal and to define what the maximum acceptable preservation
      period is for the marginal liver to minimize early graft dysfunction. METHODS:
      The authors performed an analysis on data collected prospectively of 397
      cadaveric liver transplants. Both univariate and multivariate analyses were
      performed on donor, recipient, and perioperative factors with relation to early
      allograft dysfunction. A score was developed that classified donors into marginal
      and nonmarginal populations, and the influence of cold ischemia was determined
      for each group. RESULTS: Multivariate analysis-determined donor age and steatosis
      (moderate to severe) were independent predictors of deranged function. This
      enabled the authors to produce a scoring system to differentiate marginal donors
      with respect to risk of early allograft dysfunction as follows:
      Formula=(20.06xsteatosis)+(0.44xdonor age), cutoff 23.1. In the marginal group,
      the cutoff value of cold ischemia time was 12.6 hr. CONCLUSIONS: The authors
      developed a scoring system that classified an organ as marginal or nonmarginal
      depending on the donor age and degree of steatosis. Marginal livers have a strong
      risk of developing early allograft dysfunction with increasing cold ischemia
      times and should be transplanted within 12 hr. Cold ischemia time was not found
      to be an important factor in the development of early allograft dysfunction in
      nonmarginal donors.

PMID- 14966417
TI  - Beneficial effect of matching at the HLA-A and -B amino-acid triplet level on
      rejection-free clear graft survival in penetrating keratoplasty.
AB  - OBJECTIVE: The beneficial effect of human leukocyte antigen (HLA) matching on
      long-term prognosis in penetrating keratoplasty is now unequivocal but has to be
      weighed against the additional waiting period on an individual basis.
      HLAMatchmaker is a molecularly based algorithm for histocompatibility
      determination that can identify immunologically acceptable mismatches and thus
      potentially reduce time on the waiting list dramatically without negatively
      affecting prognosis. METHODS: The HLAMatchmaker algorithm (triplet-string
      matching) was applied on each of 545 normal-risk keratoplasties for which
      complete HLA type was known at split-level resolution. Two homogeneous groups
      were defined. Group I consisted of the 147 penetrating keratoplasties with up to
      13 triplet-string mismatches (the typical upper limit of foreign in case of a
      single HLA-A or HLA-B allele mismatch) and was compared to the remaining 398
      patients with more triplet mismatches (group II) using the Kaplan-Meier method
      and log-rank statistics. Analysis of clear graft survival on the basis of
      conventional HLA-A and HLA-B matching was performed as well. Reduction of time on
      the waiting list as compared to conventional HLA-A and HLA-B matching was
      predicted individually. RESULTS: Triplet-string matching yielded 85% rejection
      free clear graft survival 3 years after penetrating keratoplasty in group I but
      only 76% in group II (P<0.05), whereas conventional HLA-A and HLA-B matching did
      not result in any statistically significant reduction of immune reactions because
      of lack of statistical power (P=0.08). Triplet-string matching (13 mismatches
      accepted) reduces median time on the waiting list by 80%. CONCLUSIONS: Triplet
      string matching seems to improve mid- to long-term prognosis in penetrating
      keratoplasties while simultaneously reducing time on the waiting list in most
      cases. It should thus be considered for histocompatibility determination in
      penetrating keratoplasty.

PMID- 14966418
TI  - Should living-unrelated renal transplant recipients receive antibody induction?
      Results of a clinical experience trial.
AB  - BACKGROUND: Living-donor kidney transplant recipients generally do not receive
      antibody induction. Induction avoidance may not be appropriate, particularly for
      living-unrelated renal transplant (LURT) recipients, in whom matching may not be
      optimal. We compared the incidence of acute rejection and graft outcome of LURT
      recipients who were administered no induction and cadaveric renal transplant
      (CRT) recipients who were administered anti-CD25 antibody. These groups both had
      immediate graft function and similar maintenance immunosuppression. METHODS: This
      retrospective analysis included patients who received kidney transplants between
      1999 and 2000. CRT recipients received basiliximab, corticosteroids,
      mycophenolate mofetil (MMF), and delayed tacrolimus (serum creatinine <3 mg/dL).
      LURT recipients received tacrolimus (initiated pretransplantation), MMF, and
      corticosteroids. RESULTS: The analysis included 136 LURT recipients and 126 CRT
      recipients. CRT recipients included more African Americans (52.4% vs. 30.9%,
      P<0.01). LURT recipients included more patients with at least one human leukocyte
      antigen mismatch (97.8% vs. 85.7%, P<0.01). A higher acute rejection rate was
      observed in LURT recipients at both 6 months (LURT recipients 19.1% vs. CRT
      recipients 3.2%, P<0.01) and 1 year (21.3% vs. 4.0%, P<0.0004); a higher rate
      also was observed in African American LURT recipients compared with African
      American CRT recipients (35.7% vs. 4.5%, P<0.0015) at 1 year. LURT recipients
      demonstrated a threefold greater rejection risk than CRT recipients who were
      administered basiliximab (relative risk: 3.6, P<0.002). Graft survival was
      similar at 1 year. CONCLUSION: The higher rejection rates in LURT recipients (no
      induction) compared with CRT recipients (basiliximab induction), despite similar
      chronic immunosuppression (tacrolimus, MMF, and steroids) and immediate graft
      function, indicate the potential advantage of anti-CD25 induction in LURT
      protocols to reduce the risk of acute rejection.

PMID- 14966419
TI  - Epidemiologic study on the origin of cancer after kidney transplantation.
AB  - BACKGROUND: Subjects who underwent solid organ transplantation are at higher risk
      for a wide variety of cancers. METHODS: The authors investigated the origin of
      cancer in a cohort of 2,526 patients followed up for 60.7 +/- 35.6 months after
      kidney transplantation between 1990 and 2000 in seven transplant centers.
      RESULTS: One hundred four of them developed cancer. All subjects who developed
      solid cancer within 6 months after transplantation (n=10) and a group of subjects
      who developed solid cancer after 6 months posttransplant (n=10) were selected.
      Short tandem repeat analysis was performed on paraffin-embedded biopsy specimens
      of tumors and on both donor and recipient pretransplant peripheral blood.
      Biologic material was obtained in 17 of the 20 selected patients (85.0%). The
      analysis showed that 16 of 17 tumors were genetically identical to the recipient.
      CONCLUSIONS: The authors' results suggest that donor transmission of solid cancer
      is an unlikely event in their population.

PMID- 14966420
TI  - The high incidence of BK polyoma virus infection among renal transplant
      recipients in India.
AB  - BK polyoma virus causes allograft dysfunction as a result of tubulo-interstitial
      nephritis in 2% to 5% of renal transplant recipients. The incidence of BK virus
      infection among renal transplant recipients in India is unknown. We used routine
      histologic examination, immunohistochemistry, and electron microscopy to
      retrospectively screen for BK polyoma virus in 414 renal allograft biopsy
      specimens from 321 transplant recipients presenting with allograft dysfunction.
      All patients had received a combination of cyclosporine, azathioprine, and
      prednisolone. A total of 30 biopsy specimens (9.3%) were positive for BK polyoma
      virus, suggesting a high incidence of this infection in Indian transplant
      recipients. BK virus infection coexisted with acute rejection in a majority of
      patients. This is the first report of this infection among Indian renal
      transplant recipients.

PMID- 14966421
TI  - Abdominal-pelvic lymphoproliferative disease after lung transplantation:
      presentation and outcome.
AB  - BACKGROUND: Lymphoproliferative disease (LPD) is a well-recognized complication
      after lung transplantation. However, its presentation in the abdomen and pelvis
      has not been previously detailed. METHODS: We retrospectively identified cases of
      abdominal-pelvic LPD in lung transplant recipients. The cases were characterized
      clinically, and the outcomes were analyzed. RESULTS: Abdominal-pelvic LPD was
      identified in 19 of 603 adult patients who underwent lung or heart-lung
      transplantation at Barnes-Jewish Hospital between July 1, 1988 and December 31,
      2001. The median time from transplantation to the onset of LPD was 5.8 years.
      Three cases presented early after transplantation (median, 175 days), and 16
      cases presented late (median, 2,255 days). The time to diagnosis of LPD was
      significantly shorter for Epstein-Barr virus (EBV)-seronegative than for EBV
      seropositive recipients (median, 175 vs. 2255 days; log-rank, P<0.001). Seventeen
      cases were non-Hodgkin's lymphomas, one was a Burkitt's lymphoma, and one was an
      atypical lymphoid proliferation. Among the 19 cases, 12 involved the
      gastrointestinal tract and 7 occurred in other sites. Immunosuppressive therapy
      was decreased in all patients. Eleven underwent surgical resection, and nine
      received chemotherapy. Sixteen patients have died, and 14 deaths were
      attributable to LPD. The median time from the diagnosis of LPD to death was 68
      days. CONCLUSIONS: Abdominal-pelvic LPD is typically a late complication after
      lung transplantation; however, when it occurs early, it may be related to a
      primary EBV infection. This form of LPD is most frequently a non-Hodgkin's
      lymphoma, and despite aggressive therapy, the prognosis is poor.

PMID- 14966422
TI  - Right laparoscopic live donor nephrectomy: a single institution experience.
AB  - BACKGROUND: Laparoscopic live donor nephrectomy (LLDN) is increasingly used by
      transplantation centers worldwide. As in open live donor nephrectomy, the left
      kidney is preferred for LLDN; however, not all potential donors have anatomy
      conducive to left nephrectomy. The purpose of our study, therefore, was to report
      on a large, single-institution experience with right LLDN performed using a hand
      assisted, transperitoneal approach. METHODS: We performed a retrospective review
      of 40 consecutive patients who underwent transperitoneal right hand-assisted LLDN
      at our institution. Information on donor age, relation to recipient, and
      indication for right-sided donation was collected. Surgical demographics included
      operative time, warm ischemia time, and estimated blood loss. Recipients were
      followed for graft loss and for long-term renal allograft function. RESULTS: The
      indications for right-sided donor nephrectomy were a difference in split renal
      function of greater than 10%, multiple left renal vessels, and right renal cysts.
      The mean surgical time in our series was 115.8 min, with a mean estimated blood
      loss of 85.7 mL and a warm ischemia time of 116.0 seconds. Surgical and
      postoperative complications were limited. Mean serum creatinine levels in the
      recipients were 1.6 mg/dL on day 7, 1.4 mg/dL on day 30, and 1.4 mg/dL at 1 year
      after transplantation. CONCLUSIONS: Right LLDN using a hand-assisted,
      transperitoneal technique was performed with minimal morbidity and favorable
      graft function. We believe that offering hand-assisted LLDN to patients with an
      indication for right-sided donation can safely and effectively increase the pool
      of donor organs available to patients with end-stage renal disease.

PMID- 14966423
TI  - Monitoring systemic donor lymphocyte macrochimerism to aid the diagnosis of graft
      versus-host disease after liver transplantation.
AB  - BACKGROUND: The diagnosis of graft-versus-host disease (GvHD) after liver
      transplantation can be difficult because early symptoms are often nonspecific. In
      this study, the presence of donor lymphocyte macrochimerism in recipient
      peripheral blood was examined as a diagnostic aid for GvHD after cadaveric donor
      liver transplantation. METHODS: Between 1996 and 2002, 33 liver transplant
      recipients with a clinical suspicion of GvHD (skin rash, diarrhea, pyrexia,
      pancytopenia, or anemia, without an obvious alternative cause) were investigated
      for peripheral blood donor lymphocyte macrochimerism. Donor macrochimerism was
      determined at the time of first clinical presentation by a low-sensitivity
      polymerase chain reaction (PCR) to detect donor human leukocyte antigen (HLA)
      alleles using genomic DNA extracted from recipient peripheral blood. Where donor
      HLA alleles were detected, the percentage of donor T cells was quantified by two
      color flow cytometric analysis using antibodies specific for mismatched donor and
      recipient HLA alleles. The relationship between the presence or absence of donor
      lymphocyte macrochimerism and final diagnoses based on clinical and histological
      criteria was examined. RESULTS: Seven of the 33 patients were PCR positive for
      donor HLA alleles. All had macrochimerism, with donor T lymphocyte levels ranging
      from 4% to 50% of circulating lymphocytes. All seven patients had normal liver
      function tests, skin rash, and diagnosis of GvHD histologically confirmed by skin
      or gut biopsies. Twenty-six patients were PCR negative, and, in 23, an
      alternative diagnosis was eventually established. The remaining three patients
      made a rapid and spontaneous recovery with no further symptoms suggestive of
      GvHD. CONCLUSIONS: Donor lymphocyte macrochimerism was present in all patients in
      whom the diagnosis of GvHD was confirmed. In patients with symptoms consistent
      with GvHD and a negative PCR for donor HLA, an alternative diagnosis was
      eventually established or the patients recovered spontaneously. Detection of
      donor HLA alleles in recipient peripheral blood by PCR is a useful diagnostic
      tool for GvHD after liver transplantation.

PMID- 14966424
TI  - Establishment of a highly differentiated immortalized human cholangiocyte cell
      line with SV40T and hTERT.
AB  - BACKGROUND: Cholangiocytes perform an essential role in important
      pathophysiologic functions in the liver. Establishment of a human cholangiocyte
      line facilitates advances in cholangiocyte research and clinical applications for
      cell therapies. Here, we describe the immortalization of human cholangiocytes
      using serial transfection of simian virus 40 large T (SV40T) followed by human
      telomerase reverse transcriptase (hTERT). METHODS: SV40T-transduced human liver
      OUMS-21 cells were superinfected with a retroviral vector SSR#197 encoding hTERT
      and green fluorescent protein (GFP) cDNAs. Resulting cell lines were evaluated
      for gene expression, functional cholangiogenic characteristics in vitro and in
      vivo, and response to lipopolysaccharide (LPS). RESULTS: One of the SV40T- and
      hTERT-immortalized cholangiocyte clones, MMNK-1, was established. MMNK-1
      expressed cholangiocyte markers, including cytokeratin (CK)-7 and -19 and
      exhibited cholangiogenic tubule formation in a Matrigel assay. When transplanted
      into the immunodeficient mice, MMNK-1 cells developed bile duct-like structures
      in the spleen. After LPS treatment, MMNK-1 cells produced interleukin-6 and
      failed to form well-developed tubular structures in Matrigel. CONCLUSION: We have
      established an immortalized cholangiocyte cell line, MMNK-1, using SV40T and
      hTERT transduction.

PMID- 14966425
TI  - CD4+ T-cell receptor transgenic T cells alone can reject vascularized heart
      transplants through the indirect pathway of alloantigen recognition.
AB  - The vast array of epitopes presented by allografts and the diversity of T cells
      responding to them complicates mechanistic studies of rejection. To minimize
      these problems, we developed a transgenic (Tg) model system limited to a single T
      cell receptor (TCR)/peptide/major histocompatibility complex molecule. Two
      alloantigen-specific CD4 T-cell clones were used to isolate cDNA encoding the
      TCRalpha and TCRbeta chains that recognize the Kd54-68/I-Ab epitope. Two
      different TCR Tg lines were produced in C57BL/6 (B6) mice and crossed onto the
      B6.Rag1-/- background. B6.Rag1-/- recipients of T cells from TCR Tg Rag1-/-mice
      promptly rejected B10.D2, but not irrelevant B10.BR, cardiac grafts. Thus, a
      single allogeneic epitope presented by self-major histocompatibility complex
      class II is sufficient to activate TCR Tg T cells and serve as a target for
      rejection.

PMID- 14966426
TI  - Macrophage colony-stimulating factor inhibits tumor necrosis factor production
      and prolongs skin graft survival.
AB  - BACKGROUND: Despite the availability of a variety of immunosuppressive agents,
      acute rejection and infection after organ transplantation remain serious
      problems. METHODS AND RESULTS: We examined the effect of macrophage colony
      stimulating factor (M-CSF) on the production of tumor necrosis factor (TNF) in a
      Bacille de Calmette Guerin-lipopolysaccharide-challenged mouse model. Both serial
      and repeated injections of M-CSF inhibited TNF production in a dose-dependent
      manner. Electrophoretic mobility shift assay showed that M-CSF-induced inhibition
      of TNF production was a result of suppression of nuclear factor-kappaB. High-dose
      M-CSF significantly prolonged skin graft survival in mice with orthotopic
      transplantation compared with the control and low-dose M-CSF groups. The combined
      administration of low-dose M-CSF and cyclosporine also significantly prolonged
      graft survival compared with the control and low-dose single agent-treated
      groups. CONCLUSIONS: Our results indicate that M-CSF at a high dose is a potent
      inhibitor of cytokine production and can potentially be used as an
      immunosuppressive agent for allograft rejection.

PMID- 14966427
TI  - Thrombophilia associated with anti-CD154 monoclonal antibody treatment and its
      prophylaxis in nonhuman primates.
AB  - BACKGROUND: The authors previously reported thromboembolic complications
      associated with anti-CD154 monoclonal antibody (mAb) treatment in nonhuman
      primates. The underlying mechanisms of this complication and its management have
      not been established. METHODS: Eighty cynomolgus monkey renal allograft
      recipients treated with anti-CD154 mAb were studied for the incidence of
      thrombosis and its prophylaxis. RESULTS: Without anticoagulation prophylaxis,
      thromboembolic complications were seen in 5 of 11 recipients. With addition of
      perioperative heparin, the incidence was decreased to 2 of 10. No further
      improvement was observed by adding intraoperative prostaglandin (PG) E1. However,
      addition of ketorolac tromethamine to PGE1 and heparin decreased the incidence of
      thrombosis (one of eight). Most recently, the authors have found that ketorolac
      administration alone resulted in no thrombosis in 25 consecutive recipients.
      CONCLUSIONS: Ketorolac is remarkably effective in preventing thromboembolism
      associated with anti-CD154 mAb treatment, suggesting the mechanism underlying
      this complication may be related to platelet activation leading to enhanced
      aggregation.

PMID- 14966428
TI  - Development of a human pancreatic islet-transplant program through a
      collaborative relationship with a remote islet-isolation center.
AB  - BACKGROUND: With the development of the Edmonton Protocol, pancreatic islet
      transplantation (PIT) now offers insulin-dependent diabetic patients metabolic
      stability. The PIT Food and Drug Administration (FDA) regulations, pancreatic
      islet isolation (PII) techniques, and clinical PIT protocols are challenging and
      make PIT program development daunting. PURPOSE: Review of the establishment of a
      PIT program through a collaborative relationship with a remote PIT/PII center.
      METHODS: Four key elements are required: (1) development of a collaborative
      relationship with an established PIT/PII center, (2) achievement of institutional
      review board and FDA approval at both centers, (3) generation of standard
      operating procedures, and (4) development of a multidisciplinary PIT team.
      RESULTS: Securing a collaborative relationship with an experienced PIT/PII center
      permitted our program to develop in less than 18 months. Twenty-two PITs were
      completed in the first clinical year. CONCLUSIONS: Collaboration with an
      experienced PIT/PII center allows developing programs to focus on patient safety
      and care, prudent use of pancreata, and consolidates PII expertise and
      experience.

PMID- 14966429
TI  - West Nile virus encephalitis in organ transplant recipients: another high-risk
      group for meningoencephalitis and death.
AB  - West Nile virus infection has been spreading westward across the continental
      United States since 1999. Although it often presents as a mild, self-limiting
      viral illness, it can result in a devastating meningoencephalitis in some patient
      populations, particularly the elderly. We report in this article on two
      immunosuppressed transplant patients who developed a severe meningoencephalitis
      caused by mosquito-borne West Nile virus infection. Suggestions for the
      prevention, diagnosis, and treatment of West Nile virus infection in this patient
      population are described.

PMID- 14966430
TI  - Acute rejection after renal transplantation is reduced by approximately 50% by
      prior therapeutic blood transfusions, even in tacrolimus-treated patients.
AB  - BACKGROUND: The authors investigated the relationship between therapeutic blood
      transfusion before renal transplantation and rejection rates in cyclosporine- and
      tacrolimus-treated patients. METHODS: In one center, 265 consecutive recipients
      were studied. Protocol induction was with azathioprine, prednisolone, and
      cyclosporine or tacrolimus; 37% had biopsy-proven acute rejection in the first 6
      months and 46% had received zero to two units of blood before transplantation.
      RESULTS: Lower risk of rejection was associated with tacrolimus induction (odds
      ratio [OR], 0.53; 95% confidence interval [CI], 0.29-0.95; P=0.049), prior
      transfusion of three or more units of blood (OR, 0.54; 95% CI, 0.33-0.90;
      P=0.024), and older age at transplantation (mean, 44.23 +/- 12.56 [+/- SD] years
      vs. 38.96 +/- 12.37 years; P=0.001). Multiple logistic regression modeling showed
      the effect of three or more prior transfusions on acute rejection was as follows:
      OR, 0.49; 95% CI, 0.29 to 0.83; P=0.008. CONCLUSIONS: Induction immunosuppression
      should take account of the higher risk of rejection in patients coming to
      transplantation who have previously received zero to two units of blood.

PMID- 14966431
TI  - Favourable outcome of adefovir-dipivoxil treatment in acute de novo hepatitis B
      after liver transplantation.
AB  - Adefovir-dipivoxil has been shown to be effective against lamivudine-resistant
      mutants in immunocompetent patients and in a small number of liver transplant
      recipients with recurrent hepatitis B virus (HBV) infection. The therapeutic role
      of adefovir-dipivoxil in acute de novo HBV infection after transplantation is
      uncertain. We describe a case of acute de novo HBV infection that occurred after
      liver transplantation and that was treated with lamivudine followed (when viral
      escape mutants emerged) by adefovir-dipivoxil rescue. Treatment outcome was
      excellent, with complete viral clearance and development of a protective titer of
      antibodies to anti-hepatitis B surface antigen. Because the donor was vaccinated
      against HBV, it is conceivable that clearance of HBV infection in the recipient
      might have been favored by adoptive transfer of immunity to HBV. The immune
      status of the donor might be a factor to consider when determining the treatment
      options for de novo hepatitis B.

PMID- 14966432
TI  - Sirolimus and ketoconazole co-prescription in renal transplant recipients.
AB  - Ketoconazole inhibits cytochrome P 3A4, leading to a 10-fold increase in
      sirolimus blood levels. Although it has not been reported in the clinical setting
      so far, sirolimus and ketoconazole co-prescription can lead to cost saving by
      reducing the dose of sirolimus administered. After informed consent was obtained,
      sirolimus and ketoconazole co-prescription was studied in six patients who could
      not afford the current recommended doses. Patients received one-eighth to one
      fourth of the recommended dose of sirolimus (0.25-0.5 mg) with 100 to 200 mg of
      ketoconazole. Sirolimus levels were monitored, and the dose of ketoconazole was
      increased to achieve target levels of sirolimus. The loading dose was 3 mg of
      sirolimus with 100 mg of ketoconazole. After sirolimus rescue therapy was
      started, serum creatinine decreased in five patients. The mean serum creatinine
      for the group decreased from 2.6 +/- 0.3 mg/dL at the initiation of rescue
      therapy to 2.2 +/- 0.5 mg/dL on the last follow-up. Sirolimus ketoconazole co
      prescription with monitoring of sirolimus levels is possible and safe and needs
      to be explored further.

PMID- 14966433
TI  - Toll-like receptor-4 and allograft responses.
AB  - Signaling through toll-like receptors (TLRs) is believed to be the critical first
      step in the activation of antigen presenting cells and the initiation of adaptive
      immune responses. Of these receptors, TLR-4 particularly recognizes endogenous
      agonists and may be important for allograft responses. We tested this concept
      using mice with defective function and structure of TLR-4 as recipients of grafts
      across major and minor histocompatibility barriers. The kinetics of rejection was
      the same in mutant mice and wild-type controls. Our results highlight an
      important difference between alloimmune and conventional immune responses.

PMID- 14966434
TI  - Nephron-sparing surgery for de novo renal cell carcinoma in a 19-year-old
      transplanted kidney.

PMID- 14966435
TI  - Drug-induced hypersensitivity syndrome associated with primary Epstein-Barr virus
      and human herpesvirus 6 infections in a child intestinal transplant recipient.

PMID- 14966436
TI  - Living-donor liver transplantation for polycystic liver disease.

PMID- 14966437
TI  - An alternate arterial reconstruction for pancreas transplantation.

PMID- 14966439
TI  - The Abbey pain scale: a 1-minute numerical indicator for people with end-stage
      dementia.
AB  - The need for a specialized clinical regimen for patients with dementia who
      require palliative care has only recently been recognized. Structured approaches
      to palliative care are not well developed. The recognition and treatment of pain
      is an important part of this management risk. However, pain is consistently
      underdiagnosed and undertreated in this population. A factor contributing to this
      has been a lack of appropriate tools to help recognize and document pain. This
      study sought to develop and validate an easy-to-use pain scale for use in
      residential aged care homes. The tool was developed with residents with end- or
      late-stage dementia who were unable to articulate their needs, identified by the
      registered nurses who knew them. Results showed that following pain-relief
      intervention the average pain score recorded using the scale fell by more than
      half. A paired Student's t-test showed the reduction to be highly significant
      (P<0.001). Validity and internal reliability, assessed by calculating Gamma and
      Cronbach's alpha, were found to be satisfactory. Qualitative evidence gathered
      from users of the scale indicated that it was considered a useful clinical device
      that could be completed within one minute. Further analysis of the use of the
      scale in clinical settings, testing of inter-rater reliability and examination of
      the limitations found in this study will commence early in 2004.

PMID- 14966440
TI  - Patients should choose where they want to die.

PMID- 14966441
TI  - Fatigue experience in advanced cancer: a phenomenological approach.
AB  - This study describes the experience of fatigue in patients with advanced cancer.
      A phenomenological approach was adopted to allow a fuller expression of the
      phenomenon of fatigue in the sample of six patients. Five major themes were
      identified. These were physical, psychological, social and spiritual consequences
      of fatigue, and helpful and unhelpful coping strategies. The themes demonstrate
      the complexity of fatigue, which had an all-encompassing effect on patients'
      lives. The themes were interconnected and cannot be viewed independently. For
      these patients with advanced cancer the meaning of fatigue was intertwined with
      the process of adjusting to living with a terminal illness and ultimately death.
      It was impossible for them to separate the two. Coping strategies that would
      normally be of use to fatigued individuals were shown to have little or no
      benefit. Sensitive communication about fatigue and its meaning to the patient may
      assist adjustment and generate hope.

PMID- 14966442
TI  - Audit on discharging patients from community specialist palliative care nursing
      services.
AB  - Discharging patients from community specialist palliative care services is a
      contentious issue. Although some specialist nursing teams discharge patients at
      the earliest opportunity and are open to re-referral, others retain patients as
      "pending", i.e. patients do not receive regular contact or intervention but
      remain on the caseload until a need arises. This anomaly is not surprising given
      the lack of evidence of good practice in the discharge of patients who no longer
      have specialist needs. This article describes an audit by a community specialist
      palliative care nursing team of patients discharged from their caseloads over a 6
      month period from January to June 2002. The aims of the audit were to compare the
      reasons for discharge given by the nurse specialists with existing discharge
      criteria and to provide data for guidelines for good practice in discharging
      patients. The rate of re-referral for the discharged cohort was also measured.
      There were 199 patient discharges in the audit period with 23 being re-referred
      within 6 months of discharge. The reasons for discharge were generally broader
      than the discharge criteria and the nurses frequently emphasized to the patient,
      the family and primary carers that re-referral was welcomed as needs arise. The
      need for multicentre discharge audits was also highlighted.

PMID- 14966443
TI  - A personal exploration of the power of poetry in palliative care, loss and
      bereavement.
AB  - This article is a personal reflection and exploration of the potential of poetry
      in palliative care. Poetry can help enable expression of individuals' deepest
      unspoken concerns and may provide a means of providing spiritual care. The author
      draws on her personal experience as a community nurse, together with the views of
      patients and colleagues, and discusses the literature. Some limitations to the
      use of poetry are considered, as are the skills needed to help patients use
      poetry. To illustrate the potential therapeutic value of poetry in palliative
      care, examples of poems by poets, patients and the author are included. The
      article concludes that poetry can bring about a sense of healing, and should be
      considered as a possible addition to other holistic therapies.

PMID- 14966444
TI  - Metastatic bone disease and tumour-induced hypercalcaemia: treatment options.
AB  - Metastatic bone disease in malignancy is responsible for considerable morbidity
      and mortality. Problems include debilitating bone pain and skeletal-related
      events (SREs), including tumour-induced hypercalcaemia. This article provides an
      overview of the different approaches to managing bone disease in malignancy with
      particular focus on the role of bisphosphonates. The three generations of
      bisphosphonates are discussed in relation to their role in treating bone pain and
      hypercalcaemia, and also in terms of their potential for being used in a
      prophylactic way to prevent or delay SREs.

PMID- 14966445
TI  - Should nurses in emergency care have practice boundaries?

PMID- 14966446
TI  - Nurses must be more aware of patient safety initiatives.

PMID- 14966447
TI  - Staff nurse who failed to maintain adequate standards of hygiene.

PMID- 14966448
TI  - Evidence-based care of a patient with a myocardial infarction.
AB  - Quality nursing care of the patient with a myocardial infarction is realized in
      accordance with evidence-based practice and by the willingness of nurses to
      adjust nursing practice as new evidence emerges. The framework for the holistic
      care of the patient following a myocardial infarction encompasses a comprehensive
      assessment, planning, intervention and evaluation process. The intention of this
      case study is to illustrate the rationale and evidence base underpinning the
      holistic approach to the care of this patient group.

PMID- 14966449
TI  - The effects of flying: processes, consequences and prevention.
AB  - The dangers of flying have recently been highlighted in the media; however, the
      available literature is contradictory, as are current recommendations for
      travellers. The purpose of this article is to provide an account of the research
      that has been undertaken to investigate the possible consequences of air travel.
      It will examine the effect that flying has on the body, especially the
      respiratory and circulatory systems, by studying the theoretical and empirical
      literature. The aim is to provide nurses with a sound insight into the effects of
      long-distance flying on the body, and the potential adverse
      effects/complications, such as deep vein thrombosis and pulmonary embolism, that
      may occur as a result. In addition, it provides information on the treatment
      options available and should enable nurses to give sound prophylactic advice
      after discharge. By encouraging passengers to take precautions, the number of
      people affected by flight could be reduced.

PMID- 14966450
TI  - Nursing management of stress urinary incontinence in women.
AB  - Although urinary incontinence is not a subject spoken about in general
      conversation, it is a cause of concern for many people. Stress urinary
      incontinence is common, being reported by 16.8% of women (Hunskaar et al, 2002).
      In the past, women with stress urinary incontinence were often dismissed as
      having an inevitable problem resulting from childbirth and the hormonal changes
      associated with ageing. They were often made to feel that they just had to put up
      with the problem--this is no longer the case. Conservative therapy is advocated
      as the primary intervention for those suffering with stress urinary incontinence
      and nurses are ideally placed to be a source of information and help.
      Furthermore, nurses can develop their skills in order to encompass therapies to
      become more specialist and effective. In 2000, the Department of Health (DoH)
      issued guidance on establishing integrated continence services (DoH, 2000). This
      becomes mandatory for older people from April 2004 (DoH, 2001a).

PMID- 14966451
TI  - Medicinal products and consent to treatment by the older person.

PMID- 14966452
TI  - Sharing best practice: developing a Web-based database.
AB  - This article reports on the development of a web-based interactive database that
      was designed to facilitate the dissemination of practice development, research
      and audit projects across a large NHS trust. A multidisciplinary team worked
      collaboratively to design the database in order to ensure that it incorporated
      features which made it easy for the end user. Concise structured information on
      each project was recorded and search facilities incorporated to facilitate access
      to information. Hyperlinks to other web pages on the Internet and the Trust
      intranet were created and full reports/publications of projects were included for
      those who wanted more information. The subsequent implementation across the
      organization involved promoting the database, helping practitioners develop
      skills to access information, setting up quality review procedures for projects
      and evaluating its use. The development of the database has highlighted that
      time, the availability of computers in clinical areas and skills development are
      important considerations when taking forward information technology (IT)
      initiatives.

PMID- 14966453
TI  - Communication barriers when managing a patient with a wound.
AB  - The management of a wound can prove challenging to the nurse when the needs of a
      patient are complex and there are barriers to overcome. This case study discusses
      the methods used by a community nurse when considering some of the problems that
      presented as a result of communication difficulties with a patient. The use of a
      wound assessment tool proved valuable when collecting and organizing information
      and the importance of gaining adequate information at assessment is outline. The
      article shows how communication impacts on the quality of care given, and how it
      affects the experiences of both nurse and patients, especially when the
      psychological and physical aspects of care are both equally demanding. The need
      for nurse and patient to work in concordance is reflected on as one of the
      lessons learnt from this case study.

PMID- 14966454
TI  - Will infection be reduced in the coming year?

PMID- 14966455
TI  - New Year resolutions for the NHS.

PMID- 14966456
TI  - Sharing the burden: the complex practice of wound care in the community.
AB  - Wound care in the community setting is often far from simple. Chronic wounds are
      the product of a complex interplay of processes that must all be addressed if
      healing, or an improvement in quality of life, is to be achieved. This case study
      highlights some of the complex issues faced in the community, and reinforces the
      need for all health professionals to continuously update their knowledge and
      skills.

PMID- 14966457
TI  - Health-related beliefs and behaviours of health visitors in Scotland.
AB  - There is some evidence that health professionals' performance of health promotion
      activities is strongly influenced by their own health beliefs and health-related
      behaviours. In the light of the current trend in health policies in Scotland and
      elsewhere towards a health promotion focus, this study sought to gain a
      description of, and to identify an association between, health beliefs and health
      related behaviours among a sample of Scottish health visitors. A questionnaire
      was sent to randomly selected health visitors in a large Scottish city.
      Respondents reported behaviours they believed to be important to health, e.g. not
      driving under the influence of alcohol, dental care and smoking. While the health
      visitors' own performance of some health-related behaviours, such as smoking, was
      associated with their health beliefs, others such as drinking coffee, were not.
      Health visitors could be advised to reconsider some of their health beliefs, in
      particular those related to areas where the government has focused its attention.

PMID- 14966458
TI  - Cytotoxic chemotherapy in the home: a study of community nurses' attitudes and
      concerns.
AB  - Cytotoxic chemotherapy initiated in a hospital setting and continued in the home
      is an expanding service. The evolution of such a service received a boost with
      the publication of the NHS Cancer Plan (Department of Health (DH), 2000a) and the
      NHS Manual of Cancer Service Standards (DH, 2000b). The literature claims a range
      of benefits of such a service including enhanced standards of care and cost
      savings. Effective care depends on a number of key factors including assessment,
      management of risk and support, i.e. appropriate policies and the availability of
      adequate resources. This study among community nurses reveals a number of key
      findings including the incremental nature of the development of policy and
      practice, the general acceptance that changes in community practice are
      inevitable and welcome where the changes enhance the care of patients, and a
      level of concern about the availability of appropriate resources and structures
      necessary for safe and effective practice.

PMID- 14966459
TI  - Cytotoxic chemotherapy: what do community nurses need to know?
AB  - Among the range of increasingly complex care demands made of community nurses in
      the UK is the support of patients undergoing cytotoxic chemotherapy at home. The
      NHS Cancer Plan and associated standards (Department of Health, 2000a,b) have
      identified that community nurses need an increased awareness and knowledge of the
      procedures and drugs involved to ensure a quality service provision. This
      article, based on a validated education course commissioned for community nurses
      in East Berkshire, explores key areas that enable community staff to care for and
      support patients through the course of their treatment and allows them to begin
      identifying an operational structure that promotes a quality service. Health and
      safety (as part of risk management) routes of administration, recognizing
      neutropenic sepsis associated with chemotherapy, and communication and
      collaboration are presented as key points identified from the course.

PMID- 14966460
TI  - Court appearance 2: Presenting oral evidence in court.
AB  - Mary Harris, a community children's nurse, has been concerned for sometime that
      two of her patients are being abused. She is required to give evidence at the
      family proceedings court. Mary is very apprehensive as this is her first court
      appearance. Last month Mary prepared for her appearance by looking at the
      structure and rules of the court. She also considered the criteria that had to be
      satisfied before magistrates could grant an order.

PMID- 14966461
TI  - So you want to do research? 6: Reporting research.
AB  - This last article of the series reviews some of the key issues that need to be
      considered when preparing your research findings for dissemination. Dissemination
      is an integral part of the research process and this article outlines some of the
      initial steps that need to be taken, including the establishment of agreements
      between authors. The importance of writing for a specific audience and how this
      determines the content of the report is then discussed. An overview together with
      guidelines on how to report qualitative and quantitative research is presented.
      General guidance on the choice of title, writing an abstract, listing references
      and acknowledgements are discussed. The article concludes with an outline of some
      of the key criteria editors use when reviewing a paper for publication.

PMID- 14966462
TI  - The nation needs to change its habits.

PMID- 14966463
TI  - Interleukin-1beta up-regulates the expression of thrombopoietin and transcription
      factors c-Jun, c-Fos, GATA-1, and NF-E2 in megakaryocytic cells.
AB  - The multifunctional cytokine interleukin-1beta (IL-1beta) plays a central role in
      the body's immune and inflammatory responses. The mechanism of IL-1beta on
      thrombocytosis and megakaryocytopoiesis has remained controversial. In previous
      reports, we have demonstrated the expression of IL-1 receptors (IL-1RI and IL
      1RII) and enhancing effects of IL-1beta on primary human megakaryocytic (MK)
      cells. In this study, we investigated the possible direct effects of IL-1beta on
      the expression of thrombopoietin (TPO) and transcription factors c-Jun, c-Fos,
      GATA-1, and p45 nuclear factor-E2 (NF-E2) in MK cell lines CHRF and Meg-01. Our
      results demonstrated that IL-1beta up-regulated messenger RNA (mRNA) and protein
      expressions of these transcription factors in a dose- and time-dependent manner.
      In CHRF cells, mRNA: c-Jun [3.4-fold, peaked at 15 minutes], c-Fos [4.2-fold, 15
      minutes], GATA-1 [4.0-fold, 60 minutes], NF-E2 [3.2-fold, 120 minutes] and
      protein expression: c-Jun [3.0-fold, 30 minutes], c-Fos [1.7-fold, 30 minutes],
      GATA-1 [11.5-fold, 60 minutes], NF-E2 [12.5-fold, 120 minutes] were evidently
      enhanced after treatment with IL-1beta. The response to IL-1beta was consistent
      in the total cell and nuclear extracts and was significantly reduced by
      pretreatment with actinomycin D or cycloheximide. An IL-1-receptor antagonist (IL
      1RA) inhibited the stimulatory effects of IL-1beta on these transcription factors
      by as much as 78%. TPO expression was increased by more than 9.9-fold on
      stimulation with IL-1beta. A TPO-neutralizing antibody did not significantly
      reduce the effects of IL-1beta. We conclude that IL-1beta up-regulates the
      expression of TPO, c-Jun, c-Fos, GATA-1, and NF-E2 in MK cells. The mechanism
      might be mediated by IL-1beta receptors and require transcription or protein
      synthesis. The direct involvement of IL-1beta in the MK lineage may provide an
      explanation for the phenomenon of thrombocytosis during inflammatory responses.

PMID- 14966464
TI  - Gene expression in aggressive fibromatosis.
AB  - Aggressive fibromatosis represents a group of tumors with heterogeneous patterns
      of biologic behavior. In this study, gene expression in 12 samples of aggressive
      fibromatosis, as well as that in samples of normal skeletal muscle and a variety
      of normal tissues, was determined at Gene Logic Inc (Gaithersburg, MD), with the
      use of Affymetrix GeneChip U_133 arrays containing approximately 33,000 genes.
      Gene-expression analysis was performed with the Gene Logic Gene Express software
      system. Differences in gene expression were quantified as the fold change in gene
      expression between the sets of fibromatosis tissue and normal skeletal muscle. A
      set of genes was then identified that was significantly overexpressed in
      aggressive fibromatosis compared with expression in normal muscle. This set of
      genes was then further examined for expression in a variety of normal tissues. We
      identified genes that were selectively overexpressed in aggressive fibromatosis
      compared with expression in 448 samples comprising 16 different nonneoplastic
      tissues. In particular, ADAM12, WISP-1, SOX-11, and fibroblast activation protein
      alpha were uniquely overexpressed in aggressive fibromatosis compared with
      expression in normal tissues. In addition, the technique of Eisen clustering
      identified 2 distinct subgroups of aggressive fibromatosis with regard to gene
      expression. We conclude that gene-expression patterns may be useful in the
      further classification of subtypes of aggressive fibromatosis and that such
      classification could have clinical significance.

PMID- 14966465
TI  - Intense lipid peroxidation in premature clinical coronary atherosclerosis is
      associated with metabolic abnormalities.
AB  - Increased oxidative stress is associated with rapid progression of
      atherosclerosis. In this study we sought to determine whether premature onset of
      clinical coronary atherosclerosis is associated with increased levels of lipid
      peroxidation. We measured plasma levels of malondialdehyde (MDA), using high
      pressure liquid chromatography, in 42 male patients with early- (<56 years) or
      late-onset (>64 years) unstable angina and in 2 age-matched control groups
      (n=20). Plasma MDA levels were higher in the patients with unstable angina than
      in the control groups (1.57 +/- 0.07 vs 1.14 +/- 0.03 nmol/mL; P<.001). Patients
      with early-onset angina showed higher MDA levels than those in late-onset
      patients (1.75 +/- 0.11 vs 1.44 +/- 0.097 nmol/mL; P<.05), despite a similar
      prevalence of risk factors for atherothrombosis. The inflammatory component,
      measured with the use of a high-sensitivity enzyme-linked immunosorbent assay for
      C-reactive protein, and platelet activity, measured as prothrombin fragment 1+2,
      failed to predict MDA level. Fasting glucose (P<.05) was the best predictor of
      MDA level in patients with early-onset unstable angina; uric acid (P=.09) and
      body-mass index (P=.15) showed trends toward significant correlation with MDA
      level in the same group of patients. Metabolic abnormalities related to insulin
      resistance in patients with premature coronary atherosclerosis appear to be
      important mediators of major plasma oxidative damage.

PMID- 14966466
TI  - Altered expression of NDST-1 messenger RNA in puromycin aminonucleoside
      nephrosis.
AB  - Sulfated portions of glycosaminoglycan (GAG) side chains in heparan sulfate
      proteoglycan (HSPG) are thought to play an important role in charge-dependent
      selectivity of glomerular filtration against plasma proteins. Heparan sulfate N
      acetylglucosamine N-deacetylase/adenosine 3'-phosphate 5'-phosphosulfate:
      unsubstituted glucosamine N-sulfotransferase (NDST) is the key enzyme regulating
      sulfation of GAG chains. In this study we investigated transcriptional expression
      of NDST-1, 1 of 4 isozymes of NDST, in glomeruli of rats with puromycin
      aminonucleoside (PAN) nephrosis. Nephrosis was induced in rats with a single
      intraperitoneal injection of 150 mg/kg PAN. On days 10 and 35, expression of NDST
      1 messenger RNA (mRNA) in glomeruli was analyzed with the use of Northern-blot
      analysis. Immunohistochemical studies were also performed with the use of
      monoclonal antibodies that react specifically with the N-sulfated portion of the
      GAG chain of HSPG and agrin, a major core protein of HSPG in glomerular basement
      membrane (GBM). In addition, we studied the expression of NDST-1 mRNA in cultured
      glomerular epithelial cells (GECs) and glomerular mesangial cells in the presence
      of PAN. On day 10, when significant proteinuria developed, the ratios of
      glomerular expression of NDST-1 mRNA against glyceraldehyde-phosphate
      dehydrogenase mRNA in PAN-treated rats were decreased to 48% +/- 6% of those in
      controls (P<.05). Immunohistochemical studies revealed that staining for N
      sulfated GAG chains of HSPG on GBM was markedly reduced on day 10 in PAN-treated
      rats but that staining for agrin was unchanged. In contrast, on day 35, when PAN
      treated rats recovered from proteinuria, we noted no differences in glomerular
      expression of NDST-1 mRNA and staining intensity for N-sulfated GAG chains on GBM
      between PAN-treated rats and controls. Incubation of GECs for 24 hours in the
      presence of 50 ng/mL PAN resulted in the reduction of the expression of NDST-1
      mRNA (67% +/- 12% of those in controls, P<.05). In summary, we found alteration
      of the expression of NDST-1 mRNA, accompanying a loss of N-sulfated GAG chains of
      HSPG on GBM without changes in the core protein agrin, in the course of PAN
      nephrosis. These data suggest an important role for this enzyme in heparan
      sulfate assembly in GBM and GEC and in the pathogenesis of proteinuria in PAN
      nephrosis.

PMID- 14966467
TI  - A covalently linked recombinant albumin dimer is more rapidly cleared in vivo
      than are wild-type and mutant C34A albumin.
AB  - Mammalian albumins are abundant plasma proteins that exhibit a relatively slow
      terminal clearance. For this reason they have been fused to potentially
      therapeutic proteins with rapid terminal clearance to produce fusion proteins
      with more desirable clearance profiles. A disulfide-linked albumin dimer has been
      described, but its abundance and stability in plasma are uncertain. To determine
      whether an obligatory albumin dimer incapable of dissociation would clear less
      rapidly than monomeric albumin, we expressed 3 recombinant rabbit serum albumin
      (RSA) polypeptides: H6RSA, RSA modified by the addition of an N-terminal
      hexahistidinyl tag; H6RSA(C34A), H6RSA with a single cysteine (Cys) 34-to-alanine
      (Ala) substitution (C34A); and DiRSA, H6RSA(C34A) joined by way of its C-terminus
      to RSA(C34A) through an intervening hexaglycine spacer. The C34A mutation was
      introduced to eliminate the possibility of disulfide bond-mediated dimerization.
      We expressed the proteins with the use of the yeast Pichia pastoris and purified
      them using nickel-chelate, ion exchange, and gel-filtration chromatography. After
      radioiodination and injection into rabbits, H6RSA and H6RSA(C34A) exhibited
      indistinguishable terminal catabolic half-lives (4.9 +/- 0.7 and 4.8 +/- 0.5
      days, mean +/- SD), whereas that of DiRSA was reduced to 3.0 +/- 0.3 days
      (p<.05). The three proteins circulated in intact form, and their distributions in
      liver, lung, kidney, heart, and spleen did not differ 24 hours after injection.
      Although more DiRSA than H6RSA(C34A) was present in urine, in both cases it was
      in acid-soluble form. Ethyl palmitate treatment reduced the relative acceleration
      of DiRSA clearance compared with that of H6RSA(C34A), suggesting a role for the
      reticuloendothelial system in the differential clearance of the larger protein.
      Our results suggest that an albumin fusion protein should include only a single
      copy of albumin; that if the fusion protein exceeds a certain size, it may not
      acquire the slow clearance profile of native albumin; and that albumin
      dimerization through Cys34 probably does not contribute substantially to albumin
      metabolism in vivo.

PMID- 14966468
TI  - Detection of bcr-abl gene expression at a low level in blood cells of some
      patients with essential thrombocythemia.
AB  - The major bcr-abl fusion gene is seen as a major marker of chronic myeloid
      leukemia (CML). However, whether the bcr-abl transcript can be detected in
      patients with essential thrombocythemia (ET) is still a matter of controversy. We
      detected the messenger RNA expression of the bcr-abl gene using reverse
      transcription-polymerase chain reaction in peripheral-blood leukocytes (PBLs)
      from 63 patients with myeloproliferative disorders (including CML, ET, and
      polycythemia vera [PV]) and 51 normal, healthy volunteers. The bcr-abl transcript
      was detected in 4 of the 30 ET patients (13.3%), 17 of the 17 CML patients
      (100%), none of the 16 PV patients (0%), and 1 of the 51 normal subjects (1.9%).
      Compared with the normal controls, ET patients have a greater tendency to express
      the bcr-abl transcript in PBLs (P=.06, Fisher's exact test). Further
      semiquantitative analysis showed that the intensity of bcr-abl transcript
      expression in 4 ET patients and a normal individual was 10(3) to 10(4) times less
      than that in the CML patients. We conclude that the bcr-abl transcript can be
      detected in the PBLs of Philadelphia chromosome (Ph)-negative ET patients but
      that the level of expression is markedly less than that in CML patients. The
      clinical significance of this finding merits further investigation.

PMID- 14966469
TI  - Are there problems with the "time compressed model" of iron overload?

PMID- 14966470
TI  - Translational research in psychiatry: pitfalls and opportunities for career
      development.

PMID- 14966473
TI  - Human catechol O-methyltransferase genetic variation: gene resequencing and
      functional characterization of variant allozymes.
AB  - Catechol O-methyltransferase (COMT) plays an important role in the metabolism of
      catecholamines, catecholestrogens and catechol drugs. A common COMT G472A genetic
      polymorphism (Val108/158Met) that was identified previously is associated with
      decreased levels of enzyme activity and has been implicated as a possible risk
      factor for neuropsychiatric disease. We set out to 'resequence' the human COMT
      gene using DNA samples from 60 African-American and 60 Caucasian-American
      subjects. A total of 23 single nucleotide polymorphisms (SNPs), including a novel
      nonsynonymous cSNP present only in DNA from African-American subjects, and one
      insertion/deletion were observed. The wild type (WT) and two variant allozymes,
      Thr52 and Met108, were transiently expressed in COS-1 and HEK293 cells. There was
      no significant change in level of COMT activity for the Thr52 variant allozyme,
      but there was a 40% decrease in the level of activity in cells transfected with
      the Met108 construct. Apparent K(m) values of the WT and variant allozymes for
      the two reaction cosubstrates differed slightly, but significantly, for 3,4
      dihydroxybenzoic acid but not for S-adenosyl-L-methionine. The Met108 allozyme
      displayed a 70-90% decrease in immunoreactive protein when compared with WT, but
      there was no significant change in the level of immunoreactive protein for Thr52.
      A significant decrease in the level of immunoreactive protein was also observed
      in hepatic biopsy samples from patients homozygous for the allele encoding
      Met108. These observations represent steps toward an understanding of molecular
      genetic mechanisms responsible for variation in COMT level and/or properties,
      variation that may contribute to the pathophysiology of neuropsychiatric disease.

PMID- 14966474
TI  - Genome-wide scan for loci of Asperger syndrome.
AB  - Asperger syndrome (AS), characterised by inadequate social interaction, lack of
      empathy and a dependence of routines and rituals, is classified as belonging to
      the autism spectrum disorders (DSM-IV and ICD-10). Although the prevalence of AS
      has been estimated to range from 0.3 up to 48.4 per 10 000, the phenotype still
      remains relatively unrecognised by clinicians. Several reports, including the
      original description by Hans Asperger (1944), have suggested that AS has a strong
      genetic component. Here, we have performed a genome-wide scan on Finnish families
      ascertained for AS with a strictly defined phenotype. In the initial scan,
      Z(max)>1.5 was observed on nine chromosomal regions, 1q21-22, 3p14-24, 3q25-27,
      4p14, 4q32, 6p25, 6q16, 13q31-33 and 18p11. In the fine mapping stage, the
      highest two-point LOD scores were observed on chromosomes 1q21-22 (D1S484, Z(max
      dom)=3.58), 3p14-24 (D3S2432, Z(max dom)=2.50) and 13q31-33 (D13S793, Z(max
      dom)=1.59). The loci on 1q21-22 and 3p14-24 overlap with previously published
      autism susceptibility loci, and the loci on 1q21-22 and 13q31-33 overlap with the
      reported schizophrenia susceptibility loci. The present study is the first genome
      wide screen in AS and therefore replication data sets are needed to evaluate
      further the significance of the AS-loci identified here.

PMID- 14966475
TI  - Follow-up of genetic linkage findings on chromosome 16p13: evidence of
      association of N-methyl-D aspartate glutamate receptor 2A gene polymorphism with
      ADHD.
AB  - Attention deficit hyperactivity disorder (ADHD) is a childhood onset disorder,
      for which there is good evidence that genetic factors contribute to the
      aetiology. Recently reported linkage findings suggested evidence of a
      susceptibility locus on chromosome 16p13 (maximum LOD score of 4.2, P=5 x 10(
      6)). The GRIN2A (glutamate receptor, ionotropic, N-methyl D-aspartate 2A) gene
      that encodes the N-methyl D-aspartate receptor subunit 2A (NMDA2A) maps to this
      region of linkage. As this is also a good functional candidate gene for ADHD, we
      undertook family-based association analysis in a sample of 238 families. We found
      significant evidence of association with a GRIN2A exon 5 polymorphism
      (chi(2)=5.7, P=0.01). Our data suggest that genetic variation in GRIN2A may
      confer increased risk for ADHD and that this, at least in part, might be
      responsible for the linkage result on 16p reported by Smalley et al. We conclude
      that replication is required and that further work examining for association of
      GRIN2A polymorphisms with ADHD is warranted.

PMID- 14966476
TI  - Upregulation of CB1 receptors and agonist-stimulated [35S]GTPgammaS binding in
      the prefrontal cortex of depressed suicide victims.
AB  - Endogenous and exogenous cannabinoids (CBs) acting through the CB(1) receptors
      have been implicated in the regulation of several behavioral and neuroendocrine
      functions. Modulation of endocannabinoidergic system by ethanol in mouse brain,
      and the association of suicide and mood disorders with alcoholism suggest
      possible involvement of the cannabinoidergic system in the pathophysiology of
      depression and suicide. Therefore, the present study was undertaken to examine
      the levels of CB(1) receptors and mediated signaling in the dorsolateral
      prefrontal cortex (DLPFC) of subjects with major depression who had died by
      suicides (depressed suicides, DS). [(3)H]CP-55,940 and CB(1) receptor-stimulated
      [(35)S]GTPgammaS binding sites were analyzed in membranes obtained from DLPFC of
      DS (10) and matched normal controls (10). Upregulation (24%, P<0.0001) of CB(1)
      receptor density (B(max)) was observed in DS (644.6+/-48.8 fmol/mg protein)
      compared with matched controls (493.3+/-52.7 fmol/mg protein). However, there was
      no significant alteration in the affinity of receptor (DS; 1.14+/-0.08 vs
      control; 1.12+/-0.10 nM). Higher density of CB(1) receptors in DS (38%, P<0.001)
      was also demonstrated by Western blot analysis. The CB(1) receptor-stimulated
      [(35)S]GTPgammaS binding was significantly greater (45%, P<0.001) in the DLPFC of
      DS compared with matched controls. The observed upregulation of CB(1) receptors
      with concomitant increase in the CB(1) receptor-mediated [(35)S]GTPgammaS binding
      suggests a role for enhanced cannabinoidergic signaling in the prefrontal cortex
      of DS. The cannabinoidergic system may be a novel therapeutic target in the
      treatment of depression and/or suicidal behavior.

PMID- 14966477
TI  - Linkage of bipolar affective disorder on chromosome 8q24: follow-up and
      parametric analysis.
AB  - Our group first reported a linkage finding for bipolar (BP) disorder on
      chromosome 8q24 in a study of 50 multiplex pedigrees, with an HLOD score reaching
      2.39. Recently, Cichon et al reported an LOD score of 3.62 in the same region
      using two-point parametric analysis. Subsequently, we published the results of a
      genome scan for linkage to BP disorder using a sample extended to 65 pedigrees in
      which chromosome 8q24 provided the best finding, an NPL score of 3.13,
      approaching the accepted score for suggestive linkage. We have now fine mapped
      this region of chromosome 8 in our 65 pedigrees by the addition of 19
      microsatellite markers reaching a marker density of 0.8 cM and an information
      content of 0.84. After the addition of the new data, the original NPL score
      slightly increased to 3.25. Two-point parametric analysis using the model
      employed by Cichon et al obtained an LOD score of 3.32 for marker D8S256 at
      theta=0.14 exceeding the proposed threshold for genomewide significance. After
      adjusting the parameters in accordance with the 'common disease-common variant'
      hypothesis, multipoint parametric analysis resulted in an HLOD of 2.49
      (alpha=0.78) between D8S529 and D8S256, and defined a 1-LOD interval
      corresponding to a 2.3 Mb region. No allelic association with the disease was
      observed for our set of microsatellite markers. Biologically, plausible candidate
      genes in this region include thyroglobulin, KCNQ3 coding for a voltage-gated
      potassium channel and the gene for brain adenyl-cyclase (ADCY8).

PMID- 14966478
TI  - A meta-analysis of the association between the serotonin transporter gene
      polymorphism (5-HTTLPR) and trait anxiety.
AB  - Studies of the association between polymorphisms of the serotonin transporter
      gene (5-HTT) and trait anxiety have produced inconsistent results, raising
      questions about the strength of the relationship and the methodological
      conditions under which the relationship holds. We conducted a meta-analysis of
      existing studies to provide formal statistical measures of the strength of the
      linked polymorphic region of the serotonin transporter gene (5-HTTLPR)-anxiety
      relationship. For the entire collection of 26 studies, results provided no
      support for a relationship between anxiety and the presence of the short form of
      the 5-HTTLPR polymorphism. There was strong evidence of the presence of
      moderating variables, however, and subsequent analysis revealed that choice of
      the measure of trait anxiety was significant. Studies using the Neuroticism scale
      of Costa and McCrae were found to produce a small positive effect (d=0.23). Other
      potential moderators (country of study origin, type of subject) did not have a
      meaningful impact on d statistics. These findings indicate that 5-HTTLPR may in
      fact have a small but reliable influence on personality, particularly in the
      manifestation of trait anxiety when measured with a neuroticism scale based on
      the five-factor model of personality. Our results suggest that the success of
      future personality genetics research will be maximized by the use of personality
      measures from both the psychobiological and five-factor models.

PMID- 14966479
TI  - Examination of G72 and D-amino-acid oxidase as genetic risk factors for
      schizophrenia and bipolar affective disorder.
AB  - A recent study has suggested that the brain-expressed genes for G72 and D-amino
      acid oxidase (DAAO) exert an influence on susceptibility to schizophrenia. Our
      aim was to replicate this finding in German schizophrenic patients and to assess
      whether G72 and DAAO might also contribute to the development of bipolar
      affective disorder. We genotyped seven single-nucleotide polymorphisms (SNPs) in
      the G72 gene and three in the DAAO gene in 599 patients (299 schizophrenic, 300
      bipolar) and 300 controls. At G72, individual SNPs and a four-marker haplotype
      were associated with schizophrenia. The most significant SNP as well as the
      haplotype were also associated with bipolar affective disorder (BPAD). DAAO was
      associated with schizophrenia, but not with BPAD. The association of variation at
      G72 with schizophrenia as well as BPAD provides molecular support for the
      hypothesis that these two major psychiatric disorders share some of their
      etiologic background.

PMID- 14966480
TI  - Confirmation and refinement of an 'at-risk' haplotype for schizophrenia suggests
      the EST cluster, Hs.97362, as a potential susceptibility gene at the Neuregulin-1
      locus.
AB  - Two recent association studies have implicated the neuregulin-1 gene (NRG1) at
      chromosome 8p21-22 as a susceptibility gene for schizophrenia. Stefansson et al
      identified three 'at-risk' haplotypes (HapA, B and C) which spanned the NRG1
      locus and shared a common core haplotype. Subsequently, they demonstrated
      evidence that the core haplotype was associated with schizophrenia in an
      independent Scottish sample. To confirm and refine this haplotype we investigated
      the NRG1 locus in an independent Irish case-control sample. We did not find the
      core haplotype to be associated in our sample. However, we identified a refined 2
      marker haplotype (HapB(IRE)) that shared common alleles with one of the Icelandic
      'at-risk' haplotypes and is in significant excess in the Irish cases (19.4%) vs
      controls (12.3%) (P=0.013). This refined 'at-risk' haplotype is also in
      significant excess in the Scottish case sample (17.0% vs 13.5%; P=0.036).
      Interestingly, this refined 'at-risk' haplotype is positioned close to an EST
      cluster of unknown function (Hs.97362) within intron 1 of NRG1.

PMID- 14966482
TI  - Apical lesions.

PMID- 14966483
TI  - Specialist training.

PMID- 14966484
TI  - Primary dentition.

PMID- 14966494
TI  - Orthodontics. Part 5: Appliance choices.
AB  - There are bewildering array of different orthodontic appliances. However, they
      fall into four main categories of removable, fixed, functional and extra-oral
      devices. The appliance has to be selected with care and used correctly as
      inappropriate use can make the malocclusion worse. Removable appliances are only
      capable of very simple movements whereas fixed appliances are sophisticated
      devices, which can precisely position the teeth. Functional appliances are useful
      in difficult cases and are primarily used for Class II Division I malocciusions.
      Extra-oral devices are used to re-enforce anchorage and can be an aid in both
      opening and closing spaces.

PMID- 14966495
TI  - The development of a model and implementation process for clinical governance in
      primary dental care.
AB  - A model and an assessment tool have been developed to support clinical governance
      within the primary care sector. These bring together quality assurance and
      governance components to create a unified standard providing a single working
      model for service development. The model consists of 14 components that define
      structure, control the process and assure the outcome. Each consists of a number
      of indicators, which are scored in turn. The results are then weighted to
      emphasise those that are more critical. The model has been tested and found to be
      helpful in identifying weak areas to support action planning. Re-scoring will
      help to demonstrate that improvements have taken place. Other services and
      practices can now carry out baseline assessments, and demonstrate and measure
      improvements. General dental practitioners are provided with a scoring system,
      which identifies clinical governance areas in their practices that require
      attention and which facilitates prioritisation.

PMID- 14966502
TI  - Colour in relation to dentistry. Fundamentals of colour science.

PMID- 14966503
TI  - The in vivo perception of roughness of restorations.
AB  - OBJECTIVE: To determine a threshold of detection value for surface roughness of
      restorations by patients using their tongue. METHOD: Samples of composite resin
      were finished with differing grades of abrasive. The surface roughness (Ra) was
      measured and representative scanning electro-micrographs taken. These were
      compared with labial enamel. Twenty-five volunteers were asked to rank them in
      order of perceived roughness using the tip of their tongue. RESULTS: These showed
      that the 60% of volunteers were able to rank the specimens correctly, and were
      able to distinguish differences in roughness values from between 0.25 and 0.50
      microm. This range encompasses that of natural enamel. CONCLUSIONS: The subjects
      were able to distinguish lower roughness values than have previously been
      reported. It is concluded that when finishing restorations the surface should
      have a maximum roughness 0.50 microm if it is not to be detected by the patient.

PMID- 14966515
TI  - Focus Award 2003 for excellence in children's dental care.

PMID- 14966516
TI  - Military dentists in Iraq.
AB  - Earlier this year, together with thousands of British troops, military dentists
      belonging to the Defence Dental Agency were deployed on operations in Iraq. Here,
      three dentists recount their stories and experiences of their time in the
      conflict and give us an insight into day to day dentistry on the frontline.

PMID- 14966518
TI  - PKC-alpha regulates cardiac contractility and propensity toward heart failure.
AB  - The protein kinase C (PKC) family of serine/threonine kinases functions
      downstream of nearly all membrane-associated signal transduction pathways. Here
      we identify PKC-alpha as a fundamental regulator of cardiac contractility and
      Ca(2+) handling in myocytes. Hearts of Prkca-deficient mice are hypercontractile,
      whereas those of transgenic mice overexpressing Prkca are hypocontractile.
      Adenoviral gene transfer of dominant-negative or wild-type PKC-alpha into cardiac
      myocytes enhances or reduces contractility, respectively. Mechanistically,
      modulation of PKC-alpha activity affects dephosphorylation of the sarcoplasmic
      reticulum Ca(2+) ATPase-2 (SERCA-2) pump inhibitory protein phospholamban (PLB),
      and alters sarcoplasmic reticulum Ca(2+) loading and the Ca(2+) transient. PKC
      alpha directly phosphorylates protein phosphatase inhibitor-1 (I-1), altering the
      activity of protein phosphatase-1 (PP-1), which may account for the effects of
      PKC-alpha on PLB phosphorylation. Hypercontractility caused by Prkca deletion
      protects against heart failure induced by pressure overload, and against dilated
      cardiomyopathy induced by deleting the gene encoding muscle LIM protein (Csrp3).
      Deletion of Prkca also rescues cardiomyopathy associated with overexpression of
      PP-1. Thus, PKC-alpha functions as a nodal integrator of cardiac contractility by
      sensing intracellular Ca(2+) and signal transduction events, which can profoundly
      affect propensity toward heart failure.

PMID- 14966519
TI  - AML-1 is required for megakaryocytic maturation and lymphocytic differentiation,
      but not for maintenance of hematopoietic stem cells in adult hematopoiesis.
AB  - Embryonic development of multilineage hematopoiesis requires the precisely
      regulated expression of lineage-specific transcription factors, including AML-1
      (encoded by Runx1; also known as CBFA-2 or PEBP-2alphaB). In vitro studies and
      findings in human diseases, including leukemias, myelodysplastic syndromes and
      familial platelet disorder with predisposition to acute myeloid leukemia (AML),
      suggest that AML-1 has a pivotal role in adult hematopoiesis. However, this role
      has not been fully uncovered in vivo because of the embryonic lethality of Runx1
      knockout in mice. Here we assess the requirement of AML-1/Runx1 in adult
      hematopoiesis using an inducible gene-targeting method. In the absence of AML-1,
      hematopoietic progenitors were fully maintained with normal myeloid cell
      development. However, AML-1-deficient bone marrow showed inhibition of
      megakaryocytic maturation, increased hematopoietic progenitor cells and defective
      T- and B-lymphocyte development. AML-1 is thus required for maturation of
      megakaryocytes and differentiation of T and B cells, but not for maintenance of
      hematopoietic stem cells (HSCs) in adult hematopoiesis.

PMID- 14966520
TI  - Reversion of CTL escape-variant immunodeficiency viruses in vivo.
AB  - Engendering cytotoxic T-lymphocyte (CTL) responses is likely to be an important
      goal of HIV vaccines. However, CTLs select for viral variants that escape immune
      detection. Maintenance of such escape variants in human populations could pose an
      obstacle to HIV vaccine development. We first observed that escape mutations in a
      heterogeneous simian immunodeficiency virus (SIV) isolate were lost upon passage
      to new animals. We therefore infected macaques with a cloned SIV bearing escape
      mutations in three immunodominant CTL epitopes, and followed viral evolution
      after infection. Here we show that each mutant epitope sequence continued to
      evolve in vivo, often re-establishing the original, CTL-susceptible sequence. We
      conclude that escape from CTL responses may exact a cost to viral fitness. In the
      absence of selective pressure upon transmission to new hosts, these original
      escape mutations can be lost. This suggests that some HIV CTL epitopes will be
      maintained in human populations.

PMID- 14966521
TI  - LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex.
AB  - Axon regeneration in the adult CNS is prevented by inhibitors in myelin. These
      inhibitors seem to modulate RhoA activity by binding to a receptor complex
      comprising a ligand-binding subunit (the Nogo-66 receptor NgR1) and a signal
      transducing subunit (the neurotrophin receptor p75). However, in reconstituted
      non-neuronal systems, NgR1 and p75 together are unable to activate RhoA,
      suggesting that additional components of the receptor may exist. Here we describe
      LINGO-1, a nervous system-specific transmembrane protein that binds NgR1 and p75
      and that is an additional functional component of the NgR1/p75 signaling complex.
      In non-neuronal cells, coexpression of human NgR1, p75 and LINGO-1 conferred
      responsiveness to oligodendrocyte myelin glycoprotein, as measured by RhoA
      activation. A dominant-negative human LINGO-1 construct attenuated myelin
      inhibition in transfected primary neuronal cultures. This effect on neurons was
      mimicked using an exogenously added human LINGO-1-Fc fusion protein. Together
      these observations suggest that LINGO-1 has an important role in CNS biology.

PMID- 14966522
TI  - Attention alters appearance.
AB  - Does attention alter appearance? This critical issue, debated for over a century,
      remains unsettled. From psychophysical evidence that covert attention affects
      early vision-it enhances contrast sensitivity and spatial resolution-and from
      neurophysiological evidence that attention increases the neuronal contrast
      sensitivity (contrast gain), one could infer that attention changes stimulus
      appearance. Surprisingly, few studies have directly investigated this issue. Here
      we developed a psychophysical method to directly assess the phenomenological
      correlates of attention in humans. We show that attention alters appearance; it
      boosts the apparent stimulus contrast. These behavioral results are consistent
      with neurophysiological findings suggesting that attention changes the strength
      of a stimulus by increasing its 'effective contrast' or salience.

PMID- 14966523
TI  - The injured spinal cord spontaneously forms a new intraspinal circuit in adult
      rats.
AB  - In contrast to peripheral nerves, central axons do not regenerate. Partial
      injuries to the spinal cord, however, are followed by functional recovery. We
      investigated the anatomical basis of this recovery and found that after
      incomplete spinal cord injury in rats, transected hindlimb corticospinal tract
      (CST) axons sprouted into the cervical gray matter to contact short and long
      propriospinal neurons (PSNs). Over 12 weeks, contacts with long PSNs that bridged
      the lesion were maintained, whereas contacts with short PSNs that did not bridge
      the lesion were lost. In turn, long PSNs arborize on lumbar motor neurons,
      creating a new intraspinal circuit relaying cortical input to its original spinal
      targets. We confirmed the functionality of this circuit by electrophysiological
      and behavioral testing before and after CST re-lesion. Retrograde transynaptic
      tracing confirmed its integrity, and revealed changes of cortical representation.
      Hence, after incomplete spinal cord injury, spontaneous extensive remodeling
      occurs, based on axonal sprout formation and removal. Such remodeling may be
      crucial for rehabilitation in humans.

PMID- 14966524
TI  - Creation of AMPA-silent synapses in the neonatal hippocampus.
AB  - In the developing brain, many glutamate synapses have been found to transmit only
      NMDA receptor-mediated signaling, that is, they are AMPA-silent. This result has
      been taken to suggest that glutamate synapses are initially AMPA-silent when they
      are formed, and that AMPA signaling is acquired through activity-dependent
      synaptic plasticity. The present study on CA3-CA1 synapses in the hippocampus of
      the neonatal rat suggests that AMPA-silent synapses are created through a form of
      activity-dependent silencing of AMPA signaling. We found that AMPA signaling, but
      not NMDA signaling, could be very rapidly silenced by presynaptic electrical
      stimulation at frequencies commonly used to probe synaptic function (0.05-1 Hz).
      Although this AMPA silencing required a rise in postsynaptic Ca(2+), it did not
      require activation of NMDA receptors, metabotropic glutamate receptors or voltage
      gated calcium channels. The AMPA silencing, possibly explained by a removal of
      postsynaptic AMPA receptors, could subsequently be reversed by paired presynaptic
      and postsynaptic activity.

PMID- 14966525
TI  - Neural correlates of sensory and decision processes in auditory object
      identification.
AB  - Physiological studies of auditory perception have not yet clearly distinguished
      sensory from decision processes. In this experiment, human participants
      identified speech sounds masked by varying levels of noise while blood
      oxygenation signals in the brain were recorded with functional magnetic resonance
      imaging (fMRI). Accuracy and response time were used to characterize the behavior
      of sensory and decision components of this perceptual system. Oxygenation signals
      in a cortical subregion just anterior and lateral to primary auditory cortex
      predicted accuracy of sound identification, whereas signals in an inferior
      frontal region predicted response time. Our findings provide neurophysiological
      evidence for a functional distinction between sensory and decision mechanisms
      underlying auditory object identification. The present results also indicate a
      link between inferior frontal lobe activation and response-selection processes
      during auditory perception tasks.

PMID- 14966526
TI  - Keeping the world a constant size: object constancy in human touch.
AB  - The perceived size of objects touching different regions of skin varies across
      the body surface by much less than is predicted from variations in tactile
      receptor density. Here we show that altering the visual experience of the body
      alters perceived tactile distances. We propose that the brain attempts to
      preserve tactile size constancy by rescaling the primary, distorted body-surface
      representation into object-centered space according to visual experience of the
      body.

PMID- 14966527
TI  - Environmental enrichment prevents effects of dark-rearing in the rat visual
      cortex.
AB  - Environmental enrichment potentiates neural plasticity, enhancing acquisition and
      consolidation of memory traces. In the sensory cortices, after cortical circuit
      maturation and sensory function acquisition are completed, neural plasticity
      declines and the critical period 'closes'. In the visual cortex, this process can
      be prevented by dark-rearing, and here we show that environmental enrichment can
      promote physiological maturation and consolidation of visual cortical connections
      in dark-reared rats, leading to critical period closure.

PMID- 14966528
TI  - Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1
      infection.
AB  - Progress in the fight against the HIV/AIDS epidemic is hindered by our failure to
      elucidate the precise reasons for the onset of immunodeficiency in HIV-1
      infection. Increasing evidence suggests that elevated immune activation is
      associated with poor outcome in HIV-1 pathogenesis. However, the basis of this
      association remains unclear. Through ex vivo analysis of virus-specific CD8(+) T
      cells and the use of an in vitro model of naive CD8(+) T-cell priming, we show
      that the activation level and the differentiation state of T-cells are closely
      related. Acute HIV-1 infection induces massive activation of CD8(+) T-cells,
      affecting many cell populations, not only those specific for HIV-1, which results
      in further differentiation of these cells. HIV disease progression correlates
      with increased proportions of highly differentiated CD8(+) T-cells, which exhibit
      characteristics of replicative senescence and probably indicate a decline in T
      cell competence of the infected person. The differentiation of CD8(+) and CD4(+)
      T-cells towards a state of replicative senescence is a natural process. It can be
      driven by excessive levels of immune stimulation. This may be part of the
      mechanism through which HIV-1-mediated immune activation exhausts the capacity of
      the immune system.

PMID- 14966530
TI  - Bridging the science-policy divide.

PMID- 14966529
TI  - pRb inactivation in mammary cells reveals common mechanisms for tumor initiation
      and progression in divergent epithelia.
AB  - Retinoblastoma 1 (pRb) and the related pocket proteins, retinoblastoma-like 1
      (p107) and retinoblastoma-like 2 (p130) (pRb(f), collectively), play a pivotal
      role in regulating eukaryotic cell cycle progression, apoptosis, and terminal
      differentiation. While aberrations in the pRb-signaling pathway are common in
      human cancers, the consequence of pRb(f) loss in the mammary gland has not been
      directly assayed in vivo. We reported previously that inactivating these critical
      cell cycle regulators in divergent cell types, either brain epithelium or
      astrocytes, abrogates the cell cycle restriction point, leading to increased cell
      proliferation and apoptosis, and predisposing to cancer. Here we report that
      mouse mammary epithelium is similar in its requirements for pRb(f) function;
      Rb(f) inactivation by T(121), a fragment of SV40 T antigen that binds to and
      inactivates pRb(f) proteins, increases proliferation and apoptosis. Mammary
      adenocarcinomas form within 16 mo. Most apoptosis is regulated by p53, which has
      no impact on proliferation, and heterozygosity for a p53 null allele
      significantly shortens tumor latency. Most tumors in p53 heterozygous mice
      undergo loss of the wild-type p53 allele. We show that the mechanism of p53 loss
      of heterozygosity is not simply the consequence of Chromosome 11 aneuploidy and
      further that chromosomal instability subsequent to p53 loss is minimal. The
      mechanisms for pRb and p53 tumor suppression in the epithelia of two distinct
      tissues, mammary gland and brain, are indistinguishable. Further, this study has
      produced a highly penetrant breast cancer model based on aberrations commonly
      observed in the human disease.

PMID- 14966531
TI  - Functional bias and spatial organization of genes in mutational hot and cold
      regions in the human genome.
AB  - The neutral mutation rate is known to vary widely along human chromosomes,
      leading to mutational hot and cold regions. We provide evidence that categories
      of functionally related genes reside preferentially in mutationally hot or cold
      regions, the size of which we have measured. Genes in hot regions are biased
      toward extracellular communication (surface receptors, cell adhesion, immune
      response, etc.), while those in cold regions are biased toward essential cellular
      processes (gene regulation, RNA processing, protein modification, etc.). From a
      selective perspective, this organization of genes could minimize the mutational
      load on genes that need to be conserved and allow fast evolution for genes that
      must frequently adapt. We also analyze the effect of gene duplication and
      chromosomal recombination, which contribute significantly to these biases for
      certain categories of hot genes. Overall, our results show that genes are located
      nonrandomly with respect to hot and cold regions, offering the possibility that
      selection acts at the level of gene location in the human genome.

PMID- 14966532
TI  - Lefty blocks a subset of TGFbeta signals by antagonizing EGF-CFC coreceptors.
AB  - Members of the EGF-CFC family play essential roles in embryonic development and
      have been implicated in tumorigenesis. The TGFbeta signals Nodal and Vg1/GDF1,
      but not Activin, require EGF-CFC coreceptors to activate Activin receptors. We
      report that the TGFbeta signaling antagonist Lefty also acts through an EGF-CFC
      dependent mechanism. Lefty inhibits Nodal and Vg1 signaling, but not Activin
      signaling. Lefty genetically interacts with EGF-CFC proteins and competes with
      Nodal for binding to these coreceptors. Chimeras between Activin and Nodal or Vg1
      identify a 14 amino acid region that confers independence from EGF-CFC
      coreceptors and resistance to Lefty. These results indicate that coreceptors are
      targets for both TGFbeta agonists and antagonists and suggest that subtle
      sequence variations in TGFbeta signals result in greater ligand diversity.

PMID- 14966533
TI  - Engineered biosynthesis of regioselectively modified aromatic polyketides using
      bimodular polyketide synthases.
AB  - Bacterial aromatic polyketides such as tetracycline and doxorubicin are a
      medicinally important class of natural products produced as secondary metabolites
      by actinomyces bacteria. Their backbones are derived from malonyl-CoA units by
      polyketide synthases (PKSs). The nascent polyketide chain is synthesized by the
      minimal PKS, a module consisting of four dissociated enzymes. Although the
      biosynthesis of most aromatic polyketide backbones is initiated through
      decarboxylation of a malonyl building block (which results in an acetate group),
      some polyketides, such as the estrogen receptor antagonist R1128, are derived
      from nonacetate primers. Understanding the mechanism of nonacetate priming can
      lead to biosynthesis of novel polyketides that have improved pharmacological
      properties. Recent biochemical analysis has shown that nonacetate priming is the
      result of stepwise activity of two dissociated PKS modules with orthogonal
      molecular recognition features. In these PKSs, an initiation module that
      synthesizes a starter unit is present in addition to the minimal PKS module. Here
      we describe a general method for the engineered biosynthesis of regioselectively
      modified aromatic polyketides. When coexpressed with the R1128 initiation module,
      the actinorhodin minimal PKS produced novel hexaketides with propionyl and
      isobutyryl primer units. Analogous octaketides could be synthesized by combining
      the tetracenomycin minimal PKS with the R1128 initiation module. Tailoring
      enzymes such as ketoreductases and cyclases were able to process the unnatural
      polyketides efficiently. Based upon these findings, hybrid PKSs were engineered
      to synthesize new anthraquinone antibiotics with predictable functional group
      modifications. Our results demonstrate that (i) bimodular aromatic PKSs present a
      general mechanism for priming aromatic polyketide backbones with nonacetate
      precursors; (ii) the minimal PKS controls polyketide chain length by counting the
      number of atoms incorporated into the backbone rather than the number of
      elongation cycles; and (iii) in contrast, auxiliary PKS enzymes such as
      ketoreductases, aromatases, and cyclases recognize specific functional groups in
      the backbone rather than overall chain length. Among the anthracyclines
      engineered in this study were compounds with (i) more superior activity than
      R1128 against the breast cancer cell line MCF-7 and (ii) inhibitory activity
      against glucose-6-phosphate translocase, an attractive target for the treatment
      of Type II diabetes.

PMID- 14966534
TI  - Cracking the polyketide code.

PMID- 14966535
TI  - Treatment of terminal peritoneal carcinomatosis by a transducible p53-activating
      peptide.
AB  - Advanced-stage peritoneal carcinomatosis is resistant to current chemotherapy
      treatment and, in the case of metastatic ovarian cancer, results in a devastating
      15%-20% survival rate. Therapeutics that restore genes inactivated during
      oncogenesis are predicted to be more potent and specific than current therapies.
      Experiments with viral vectors have demonstrated the theoretical utility of
      expressing the p53 tumor suppressor gene in cancer cells. However, clinically
      useful alternative approaches for introducing p53 activity into cancer cells are
      clearly needed. It has been hypothesized that direct reactivation of endogenous
      p53 protein in cancer cells will be therapeutically beneficial, but few tests of
      this hypothesis have been carried out in vivo. We report that a transducible D
      isomer RI-TATp53C' peptide activates the p53 protein in cancer cells, but not
      normal cells. RI-TATp53C' peptide treatment of preclinical terminal peritoneal
      carcinomatosis and peritoneal lymphoma models results in significant increases in
      lifespan (greater than 6-fold) and the generation of disease-free animals. These
      proof-of-concept observations show that specific activation of endogenous p53
      activity by a macromolecular agent is therapeutically effective in preclinical
      models of terminal human malignancy. Our results suggest that TAT-mediated
      transduction may be a useful strategy for the therapeutic delivery of large tumor
      suppressor molecules to malignant cells in vivo.

PMID- 14966536
TI  - Tumour suppressor genes--one hit can be enough.

PMID- 14966538
TI  - The effect of learning on the function of monkey extrastriate visual cortex.
AB  - One of the most remarkable capabilities of the adult brain is its ability to
      learn and continuously adapt to an ever-changing environment. While many studies
      have documented how learning improves the perception and identification of visual
      stimuli, relatively little is known about how it modifies the underlying neural
      mechanisms. We trained monkeys to identify natural images that were degraded by
      interpolation with visual noise. We found that learning led to an improvement in
      monkeys' ability to identify these indeterminate visual stimuli. We link this
      behavioral improvement to a learning-dependent increase in the amount of
      information communicated by V4 neurons. This increase was mediated by a specific
      enhancement in neural activity. Our results reveal a mechanism by which learning
      increases the amount of information that V4 neurons are able to extract from the
      visual environment. This suggests that V4 plays a key role in resolving
      indeterminate visual inputs by coordinated interaction between bottom-up and top
      down processing streams.

PMID- 14966539
TI  - Learning-induced improvement in encoding and decoding of specific movement
      directions by neurons in the primary motor cortex.
AB  - Many recent studies describe learning-related changes in sensory and motor areas,
      but few have directly probed for improvement in neuronal coding after learning.
      We used information theory to analyze single-cell activity from the primary motor
      cortex of monkeys, before and after learning a local rotational visuomotor task.
      We show that after learning, neurons in the primary motor cortex conveyed more
      information about the direction of movement and did so with relation to their
      directional sensitivity. Similar to recent findings in sensory systems, this
      specific improvement in encoding is correlated with an increase in the slope of
      the neurons' tuning curve. We further demonstrate that the improved information
      after learning enables a more accurate reconstruction of movement direction from
      neuronal populations. Our results suggest that similar mechanisms govern learning
      in sensory and motor areas and provide further evidence for a tight relationship
      between the locality of learning and the properties of neurons; namely, cells
      only show plasticity if their preferred direction is near the training one. The
      results also suggest that simple learning tasks can enhance the performance of
      brain-machine interfaces.

PMID- 14966540
TI  - What causes stuttering?

PMID- 14966541
TI  - Quality information for improved health.

PMID- 14966544
TI  - A new trade framework for global healthcare R&D.

PMID- 14966542
TI  - Design and diversity in bacterial chemotaxis: a comparative study in Escherichia
      coli and Bacillus subtilis.
AB  - Comparable processes in different species often involve homologous genes. One
      question is whether the network structure, in particular the feedback control
      structure, is also conserved. The bacterial chemotaxis pathways in E. coli and B.
      subtilis both regulate the same task, namely, excitation and adaptation to
      environmental signals. Both pathways employ many orthologous genes. Yet how these
      orthologs contribute to network function in each organism is different. To
      investigate this problem, we propose what is to our knowledge the first
      computational model for B. subtilis chemotaxis and compare it to previously
      published models for chemotaxis in E. coli. The models reveal that the core
      control strategy for signal processing is the same in both organisms, though in
      B. subtilis there are two additional feedback loops that provide an additional
      layer of regulation and robustness. Furthermore, the network structures are
      different despite the similarity of the proteins in each organism. These results
      demonstrate the limitations of pathway inferences based solely on homology and
      suggest that the control strategy is an evolutionarily conserved property.

PMID- 14966545
TI  - New antibiotics--resistance is futile.

PMID- 14966546
TI  - World on fire.

PMID- 14966553
TI  - PLoS Medicine.

PMID- 14966555
TI  - Assessing risk is the business of prion disease research.

PMID- 14966556
TI  - Human African trypanosomiasis of the CNS: current issues and challenges.
AB  - Human African trypanosomiasis (HAT), also known as sleeping sickness, is a major
      cause of mortality and morbidity in sub-Saharan Africa. Current therapy with
      melarsoprol for CNS HAT has unacceptable side-effects with an overall mortality
      of 5%. This review discusses the issues of diagnosis and staging of CNS disease,
      its neuropathogenesis, and the possibility of new therapies for treating late
      stage disease.

PMID- 14966557
TI  - Into the depths of ataxia.
AB  - Ataxia is a lethal neurological disease characterized by incoordination, postural
      abnormalities, difficulties with gait, and problems with clarity of speech. The
      etiology of ataxia is divided equally between hereditary and sporadic forms.
      Regardless of cause, the cerebellar cortex is often a target in ataxia. Thus, how
      a disruption in cerebellar cortex might lead to ataxia is of considerable
      interest. A report in this issue of the JCI links ataxia to enhanced
      hyperexcitability of neurons in the deep cerebellar nuclei.

PMID- 14966558
TI  - The eosinophil enigma.
AB  - Eosinophils accumulate in high numbers in the lungs of asthmatic patients. These
      cells have the ability to induce tissue damage, a capacity that relates to their
      traditional role in host defense against parasitic worms. On the other hand,
      eosinophils produce growth factors associated with tissue repair and remodeling,
      notably TGF-beta1. The relationship of these activities to lung dysfunction in
      asthma is highly controversial, but recent observations in humans and in animal
      models add spice to the debate.

PMID- 14966559
TI  - HDL action on the vascular wall: is the answer NO?
AB  - Circulating levels of HDL cholesterol are inversely related to the risk of
      atherosclerosis, and therapeutic increases in HDL reduce the incidence of
      cardiovascular events. A new study shows that HDL-associated lysophospholipids
      stimulate the production of the potent antiatherogenic signaling molecule NO by
      the vascular endothelium.

PMID- 14966560
TI  - Fighting cancer by disrupting C-terminal methylation of signaling proteins.
AB  - Protein methylation at the C-terminus of mammalian isoprenylated proteins has
      been implicated in membrane attachment, protein-protein interactions, and protein
      stability. A new paper describes surprising results: in the absence of
      methylation some target proteins have increased stability, whereas others have
      decreased stability. The decreased stability of the RhoA protein is correlated
      with an increased resistance to Ras-dependent transformation and suggests the
      basis for the development of a new approach to antitumor therapy.

PMID- 14966561
TI  - Microenvironmental VEGF concentration, not total dose, determines a threshold
      between normal and aberrant angiogenesis.
AB  - Use of long-term constitutive expression of VEGF for therapeutic angiogenesis may
      be limited by the growth of abnormal blood vessels and hemangiomas. We
      investigated the relationship between VEGF dosage and the morphology and function
      of newly formed blood vessels by implanting retrovirally transduced myoblasts
      that constitutively express VEGF164 into muscles of adult mice. Reducing VEGF
      dosage by decreasing the total number of VEGF myoblasts implanted did not prevent
      vascular abnormalities. However, when clonal populations of myoblasts
      homogeneously expressing different levels of VEGF were implanted, a threshold
      between normal and aberrant angiogenesis was found. Clonal myoblasts that
      expressed low to medium levels of VEGF induced growth of stable, pericyte-coated
      capillaries of uniform size that were not leaky and became VEGF independent, as
      shown by treatment with the potent VEGF blocker VEGF-TrapR1R2. In contrast,
      clones that expressed high levels of VEGF induced hemangiomas. Remarkably, when
      different clonal populations were mixed, even a small proportion of cells with
      high production of VEGF was sufficient to cause hemangioma growth. These results
      show for the first time to our knowledge that the key determinant of whether VEGF
      induced angiogenesis is normal or aberrant is the microenvironmental amount of
      growth factor secreted, rather than the overall dose. Long-term continuous
      delivery of VEGF, when maintained below a threshold microenvironmental level, can
      lead to normal angiogenesis without other exogenous growth factors.

PMID- 14966562
TI  - Conditional expression of oncogenic K-ras from its endogenous promoter induces a
      myeloproliferative disease.
AB  - Oncogenic ras alleles are among the most common mutations found in patients with
      acute myeloid leukemia (AML). Previously, the role of oncogenic ras in cancer was
      assessed in model systems overexpressing oncogenic ras from heterologous
      promoters. However, there is increasing evidence that subtle differences in gene
      dosage and regulation of gene expression from endogenous promoters play critical
      roles in cancer pathogenesis. We characterized the role of oncogenic K-ras
      expressed from its endogenous promoter in the hematopoietic system using a
      conditional allele and IFN-inducible, Cre-mediated recombination. Mice developed
      a completely penetrant myeloproliferative syndrome characterized by leukocytosis
      with normal maturation of myeloid lineage cells; myeloid hyperplasia in bone
      marrow; and extramedullary hematopoiesis in the spleen and liver. Flow cytometry
      confirmed the myeloproliferative phenotype. Genotypic and Western blot analysis
      demonstrated Cre-mediated excision and expression, respectively, of the oncogenic
      K-ras allele. Bone marrow cells formed growth factor-independent colonies in
      methylcellulose cultures, but the myeloproliferative disease was not
      transplantable into secondary recipients. Thus, oncogenic K-ras induces a
      myeloproliferative disorder but not AML, indicating that additional mutations are
      required for AML development. This model system will be useful for assessing the
      contribution of cooperating mutations in AML and testing ras inhibitors in vivo.

PMID- 14966563
TI  - Inactivation of Icmt inhibits transformation by oncogenic K-Ras and B-Raf.
AB  - Isoprenylcysteine carboxyl methyltransferase (Icmt) methylates the carboxyl
      terminal isoprenylcysteine of CAAX proteins (e.g., Ras and Rho proteins). In the
      case of the Ras proteins, carboxyl methylation is important for targeting of the
      proteins to the plasma membrane. We hypothesized that a knockout of Icmt would
      reduce the ability of cells to be transformed by K-Ras. Fibroblasts harboring a
      floxed Icmt allele and expressing activated K-Ras (K-Ras-Icmt(flx/flx)) were
      treated with Cre-adenovirus, producing K-Ras-Icmt(Delta/Delta) fibroblasts.
      Inactivation of Icmt inhibited cell growth and K-Ras-induced oncogenic
      transformation, both in soft agar assays and in a nude mice model. The
      inactivation of Icmt did not affect growth factor-stimulated phosphorylation of
      Erk1/2 or Akt1. However, levels of RhoA were greatly reduced as a consequence of
      accelerated protein turnover. In addition, there was a large Ras/Erk1/2-dependent
      increase in p21(Cip1), which was probably a consequence of the reduced levels of
      RhoA. Deletion of p21(Cip1) restored the ability of K-Ras-Icmt(Delta/Delta)
      fibroblasts to grow in soft agar. The effect of inactivating Icmt was not limited
      to the inhibition of K-Ras-induced transformation: inactivation of Icmt blocked
      transformation by an oncogenic form of B-Raf (V599E). These studies identify Icmt
      as a potential target for reducing the growth of K-Ras- and B-Raf-induced
      malignancies.

PMID- 14966564
TI  - Inhibition of airway remodeling in IL-5-deficient mice.
AB  - To determine the role of IL-5 in airway remodeling, IL-5-deficient and WT mice
      were sensitized to OVA and challenged by repetitive administration of OVA for 3
      months. IL-5-deficient mice had significantly less peribronchial fibrosis (total
      lung collagen content, peribronchial collagens III and V) and significantly less
      peribronchial smooth muscle (thickness of peribronchial smooth muscle layer,
      alpha-smooth muscle actin immunostaining) compared with WT mice challenged with
      OVA. WT mice had a significant increase in the number of peribronchial cells
      staining positive for major basic protein and TGF-beta. In contrast, IL-5
      deficient mice had a significant reduction in the number of peribronchial cells
      staining positive for major basic protein, which was paralleled by a similar
      reduction in the number of cells staining positive for TGF-beta, suggesting that
      eosinophils are a significant source of TGF-beta in the remodeled airway. OVA
      challenge induced significantly higher levels of airway epithelial alphaVbeta6
      integrin expression, as well as significantly higher levels of bioactive lung TGF
      beta in WT compared with IL-5-deficient mice. Increased airway epithelial
      expression of alphaVbeta6 integrin may contribute to the increased activation of
      latent TGF-beta. These results suggest an important role for IL-5, eosinophils,
      alphaVbeta6, and TGF-beta in airway remodeling.

PMID- 14966565
TI  - Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23
      in phosphate and vitamin D metabolism.
AB  - Inorganic phosphate is essential for ECM mineralization and also as a constituent
      of important molecules in cellular metabolism. Investigations of several
      hypophosphatemic diseases indicated that a hormone-like molecule probably
      regulates serum phosphate concentration. FGF23 has recently been recognized as
      playing important pathophysiological roles in several hypophosphatemic diseases.
      We present here the evidence that FGF23 is a physiological regulator of serum
      phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D) by generating FGF23-null mice.
      Disruption of the Fgf23 gene did not result in embryonic lethality, although
      homozygous mice showed severe growth retardation with abnormal bone phenotype and
      markedly short life span. The Fgf23(-/-) mice displayed significantly high serum
      phosphate with increased renal phosphate reabsorption. They also showed an
      elevation in serum 1,25(OH)2D that was due to the enhanced expression of renal 25
      hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase) from 10 days of age. These
      phenotypes could not be explained by currently known regulators of mineral
      homeostasis, indicating that FGF23 is essential for normal phosphate and vitamin
      D metabolism.

PMID- 14966566
TI  - HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3.
AB  - HDL is a major atheroprotective factor, but the mechanisms underlying this effect
      are still obscure. HDL binding to scavenger receptor-BI has been shown to
      activate eNOS, although the responsible HDL entities and signaling pathways have
      remained enigmatic. Here we show that HDL stimulates NO release in human
      endothelial cells and induces vasodilation in isolated aortae via intracellular
      Ca2+ mobilization and Akt-mediated eNOS phosphorylation. The vasoactive effects
      of HDL could be mimicked by three lysophospholipids present in HDL:
      sphingosylphosphorylcholine (SPC), sphingosine-1-phosphate (S1P), and
      lysosulfatide (LSF). All three elevated intracellular Ca2+ concentration and
      activated Akt and eNOS, which resulted in NO release and vasodilation. Deficiency
      of the lysophospholipid receptor S1P3 (also known as LPB3 and EDG3) abolished the
      vasodilatory effects of SPC, S1P, and LSF and reduced the effect of HDL by
      approximately 60%. In endothelial cells from S1P3-deficient mice, Akt
      phosphorylation and Ca2+ increase in response to HDL and lysophospholipids were
      severely reduced. In vivo, intra-arterial administration of HDL or
      lysophospholipids lowered mean arterial blood pressure in rats. In conclusion, we
      identify HDL as a carrier of bioactive lysophospholipids that regulate vascular
      tone via S1P3-mediated NO release. This mechanism may contribute to the
      vasoactive effect of HDL and represent a novel aspect of its antiatherogenic
      function.

PMID- 14966567
TI  - Enhanced neuronal excitability in the absence of neurodegeneration induces
      cerebellar ataxia.
AB  - Cerebellar ataxia, a devastating neurological disease, may be initiated by
      hyperexcitability of deep cerebellar nuclei (DCN) secondary to loss of inhibitory
      input from Purkinje neurons that frequently degenerate in this disease. This
      mechanism predicts that intrinsic DCN hyperexcitability would cause ataxia in the
      absence of upstream Purkinje degeneration. We report the generation of a
      transgenic (Tg) model that supports this mechanism of disease initiation. Small
      conductance calcium-activated potassium (SK) channels, regulators of firing
      frequency, were silenced in the CNS of Tg mice with the dominant-inhibitory
      construct SK3-1B-GFP. Transgene expression was restricted to the DCN within the
      cerebellum and was detectable beginning on postnatal day 10, concomitant with the
      onset of cerebellar ataxia. Neurodegeneration was not evident up to the sixth
      month of age. Recordings from Tg DCN neurons revealed loss of the apamin
      sensitive after-hyperpolarization current (IAHP) and increased spontaneous firing
      through SK channel suppression, indicative of DCN hyperexcitability. Spike
      duration and other electrogenic conductance were unaffected. Thus, a purely
      electrical alteration is sufficient to cause cerebellar ataxia, and SK openers
      such as the neuroprotective agent riluzole may reduce neuronal hyperexcitability
      and have therapeutic value. This dominant-inhibitory strategy may help define the
      in vivo role of SK channels in other neuronal pathways.

PMID- 14966568
TI  - Vanin-1(-/-) mice show decreased NSAID- and Schistosoma-induced intestinal
      inflammation associated with higher glutathione stores.
AB  - Vanin-1 is a membrane-anchored pantetheinase highly expressed in the gut and
      liver. It hydrolyzes pantetheine to pantothenic acid (vitamin B5) and the low
      molecular-weight thiol cysteamine. The latter is believed to be a key regulating
      factor of several essential metabolic pathways, acting through sulfhydryl
      disulfide exchange reactions between sulfhydryl groups of the enzymes and the
      oxidized form, cystamine. Its physiological importance remains to be elucidated,
      however. To explore this point, we developed Vanin-1-deficient mice that lack
      free cysteamine. We examined the susceptibility of deficient mice to intestinal
      inflammation, either acute (NSAID administration) or chronic (Schistosoma
      infection). We found that Vanin-1(-/-) mice better controlled inflammatory
      reaction and intestinal injury in both experiments. This protection was
      associated with increased gamma-glutamylcysteine synthetase activity and
      increased stores of reduced glutathione, as well as reduced inflammatory cell
      activation in inflamed tissues. Oral administration of cystamine reversed all
      aspects of the deficient phenotype. These findings suggest that one cysteamine
      function is to upregulate inflammation. Consequently, the pantetheinase activity
      of Vanin-1 molecule could be a target for a new anti-inflammatory strategy.

PMID- 14966569
TI  - The calcium-sensing receptor regulates mammary gland parathyroid hormone-related
      protein production and calcium transport.
AB  - The transfer of calcium from mother to milk during lactation is poorly
      understood. In this report, we demonstrate that parathyroid hormone-related
      protein (PTHrP) production and calcium transport in mammary epithelial cells are
      regulated by extracellular calcium acting through the calcium-sensing receptor
      (CaR). The CaR becomes expressed on mammary epithelial cells at the transition
      from pregnancy to lactation. Increasing concentrations of calcium, neomycin, and
      a calcimimetic compound suppress PTHrP secretion by mammary epithelial cells in
      vitro, whereas in vivo, systemic hypocalcemia increases PTHrP production, an
      effect that can be prevented by treatment with a calcimimetic. Hypocalcemia also
      reduces overall milk production and calcium content, while increasing milk
      osmolality and protein concentrations. The changes in milk calcium content, milk
      osmolality, and milk protein concentration were mitigated by calcimimetic
      infusions. Finally, in a three-dimensional culture system that recapitulates the
      lactating alveolus, activation of the basolateral CaR increases transcellular
      calcium transport independent of its effect on PTHrP. We conclude that the
      lactating mammary gland can sense calcium and adjusts its secretion of calcium,
      PTHrP, and perhaps water in response to changes in extracellular calcium
      concentration. We believe this defines a homeostatic system that helps to match
      milk production to the availability of calcium.

PMID- 14966570
TI  - Antimitogenic effects of HDL and APOE mediated by Cox-2-dependent IP activation.
AB  - HDL and its associated apo, APOE, inhibit S-phase entry of murine aortic smooth
      muscle cells. We report here that the antimitogenic effect of APOE maps to the N
      terminal receptor-binding domain, that APOE and its N-terminal domain inhibit
      activation of the cyclin A promoter, and that these effects involve both pocket
      protein-dependent and independent pathways. These antimitogenic effects closely
      resemble those seen in response to activation of the prostacyclin receptor IP.
      Indeed, we found that HDL and APOE suppress aortic smooth muscle cell cycle
      progression by stimulating Cox-2 expression, leading to prostacyclin synthesis
      and an IP-dependent inhibition of the cyclin A gene. Similar results were
      detected in human aortic smooth muscle cells and in vivo using mice
      overexpressing APOE. Our results identify the Cox-2 gene as a target of APOE
      signaling, link HDL and APOE to IP action, and describe a potential new basis for
      the cardioprotective effect of HDL and APOE.

PMID- 14966571
TI  - Enhancement of MEK/ERK signaling promotes glucocorticoid resistance in CD4+ T
      cells.
AB  - Glucocorticoids have potent immunosuppressive properties, but their effects are
      often modulated by the conditions prevailing in the local immune milieu. In this
      study we determined whether the action of glucocorticoids is influenced by the
      degree of signaling during T cell activation. We found that dexamethasone (Dex)
      effectively suppressed T cell receptor-induced (TCR-induced) proliferation of
      naive CD4+ T cells, through a mechanism involving downregulation of c-Fos
      expression and inhibition of activator protein-1 (AP-1), nuclear factor of
      activated T cells (NF-AT), and NF-kappaB transcriptional activity. However,
      enhancement of TCR signaling by CD28- or IL-2-mediated costimulation abrogated
      the suppressive effect of Dex on c-Fos expression and AP-1 function and restored
      cellular proliferation. The amount of signaling through the MAPK pathway was
      critical in determining the effect of Dex on T cell activation. In particular,
      costimulatory signaling via MAPK kinase (MEK) and extracellular signal-regulated
      kinase (ERK) was essential for the development of T cell resistance to Dex.
      Selective blockade of MEK/ERK signal transduction abolished the costimulation
      induced resistance. In contrast, transmission of IL-2 signals via STAT5 and CD28
      signals via NF-kappaB remained inhibited by Dex. These results imply that the
      immune system, by regulating the degree of local costimulation through MEK/ERK,
      can modify the effect of glucocorticoids on T cells. Moreover, these findings
      suggest that MAPK inhibitors may offer a therapeutic solution for glucocorticoid
      resistance.

PMID- 14966572
TI  - Mast cell dipeptidyl peptidase I mediates survival from sepsis.
AB  - Sepsis is a common, life-threatening disease for which there is little treatment.
      The cysteine protease dipeptidyl peptidase I (DPPI) activates granule-associated
      serine proteases, several of which play important roles in host responses to
      bacterial infection. To examine DPPI's role in sepsis, we compared DPPI(-/-) and
      DPPI(+/+) mice using the cecal ligation and puncture (CLP) model of septic
      peritonitis, finding that DPPI(-/-) mice are far more likely to survive sepsis.
      Outcomes of CLP in mice lacking mast cell DPPI reveal that the absence of DPPI in
      mast cells, rather than in other cell types, is responsible for the survival
      advantage. Among several cytokines surveyed in peritoneal fluid and serum, IL-6
      is highly and differentially expressed in DPPI(-/-) mice compared with DPPI(+/+)
      mice. Remarkably, deleting IL-6 expression in DPPI(-/-) mice eliminates the
      survival advantage. The increase in IL-6 in septic DPPI(-/-) mice, which appears
      to protect these mice from death, may be related to reduced DPPI-mediated
      activation of mast cell tryptase and other peptidases, which we show cleave IL-6
      in vitro. These results indicate that mast cell DPPI harms the septic host and
      that DPPI is a novel potential therapeutic target for treatment of sepsis.

PMID- 14966573
TI  - Gluco-incretins control insulin secretion at multiple levels as revealed in mice
      lacking GLP-1 and GIP receptors.
AB  - The role of the gluco-incretin hormones GIP and GLP-1 in the control of beta cell
      function was studied by analyzing mice with inactivation of each of these hormone
      receptor genes, or both. Our results demonstrate that glucose intolerance was
      additively increased during oral glucose absorption when both receptors were
      inactivated. After intraperitoneal injections, glucose intolerance was more
      severe in double- as compared to single-receptor KO mice, and euglycemic clamps
      revealed normal insulin sensitivity, suggesting a defect in insulin secretion.
      When assessed in vivo or in perfused pancreas, insulin secretion showed a lack of
      first phase in Glp-1R(-/-) but not in Gipr(-/-) mice. In perifusion experiments,
      however, first-phase insulin secretion was present in both types of islets. In
      double-KO islets, kinetics of insulin secretion was normal, but its amplitude was
      reduced by about 50% because of a defect distal to plasma membrane
      depolarization. Thus, gluco-incretin hormones control insulin secretion (a) by an
      acute insulinotropic effect on beta cells after oral glucose absorption (b)
      through the regulation, by GLP-1, of in vivo first-phase insulin secretion,
      probably by an action on extra-islet glucose sensors, and (c) by preserving the
      function of the secretory pathway, as evidenced by a beta cell autonomous
      secretion defect when both receptors are inactivated.

PMID- 14966574
TI  - [Effects and holding time of hyperbaric oxygen on human severe periodontitis].
AB  - OBJECTIVE: This paper studied the therapeutic effects and holding time of
      hyperbaric oxygen (HBO) on human severe periodontitis. METHODS: 30 cases with
      periodontitis were selected and randomly divided into 2 groups, i.e. the HBO
      group and control group. For HBO group, they were exposed to a pressure of 0.25
      MPa. For control group, they were rinsed with gargle. Gingival indices (GI),
      sulcus bleeding indices (SBI), plaque index (PLI), probing depth (PD), attachment
      loss (AL) and gingival crevicular fluid (GCF) were measured during both the first
      and last clinical visits, and 1 year after HBO therapy. The gingival blood flow
      (GBF) were measured by Laser Doppler Flowmeter. RESULTS: HBO can decrease GI of
      patients with periodontitis by 1.1 decrease SBI by 1.2, lower PD and AL by 0.7
      mm, decrease the volume of GCF by 2.0, and significant differences could be seen
      in the above indices between pre and post HBO therapy. The GBF had a 1.8 folds
      increase after HBO exposure. GI and SBI one year after HBO therapy were larger
      than that of the time after HBO therapy. There were no significant differences in
      the PLI, PD, AL, GCF, GBF between post HBO therapy and 1 year after HBO therapy.
      CONCLUSION: HBO had good therapeutic effects on human severe periodontitis, the
      effects can keep more than 1 year.

PMID- 14966575
TI  - [Cephalometric study of Holdaway analytical method by computer on 58 adults with
      normal occlusion in Chongqing].
AB  - OBJECTIVE: In order to establish the normal value of Holdaway analytical method
      of Chongqing and to reveal the regular patterns and characteristics concerning
      the craniofacial morphology. METHODS: 58 students, with permanent dentition were
      selected as the samples. The cephalometric images were scanned into a computer
      and the images were imported into the program. The cephalometric analysis were
      automated by the computer. The cephalometric analytical method of Holdaway was
      used in this study. Correlational analysis were calculated. RESULTS: The normal
      values of Holdaway analytical method for permanent denition on normal occlusal
      adults of Chongqing were established and compared with that of Pekingman,
      Japanese and White man. CONCLUSIONS: We found that soft cephalometric measurement
      values are various in sex and races and regional population. There were
      correlations between hard and soft tissues.

PMID- 14966576
TI  - [The diagnostic value of fine-needle aspiration cytology (FNAC) for lesions in
      the parotid gland].
AB  - OBJECTIVE: To evaluate the effectiveness of FNAC in the diagnosis of parotid
      gland masses. METHODS: Fine needle aspiration cytology was performed in 121
      patients with parotid gland masses. Among them, 62 were males, 59 were females.
      Their age ranged from 5 to 95 years with an average age of 57.88 years. The
      cytological results were compared with postoperative histopathological results
      and follow-up outcomes. RESULTS: The qualitative diagnostic accuracy of FNAC was
      92.56% (112/121) and the overall diagnostic accuracy was 89.26%. The sensitivity
      for tumors was 91.25%, and the specificity was 100%. 7 patients were false
      negative with a false negative rate of 8.75%. The sensitivity and specificity for
      benign and malignant lesions was 70.97% and 100%, respectively. 9 patients were
      false negative with a false negative rate of 29.03%. There were no false positive
      cases, nor clinical complications. CONCLUSIONS: FNAC plays an important role in
      the diagnosis of parotid gland masses. It is a cost-effective, safe, helpful and
      accurate tool for establishing tissue diagnosis as a primary investigative
      modality in the diagnosis of lesions in the parotid gland region with higher
      accuracy and fewer complications.

PMID- 14966577
TI  - [The application of oral digital imaging system in root canal measurement and
      filing].

PMID- 14966578
TI  - [Analysis for clinical effect of a rinse containing cetylpyridinium chloride in
      treatment of gingivitis and periodontitis].
AB  - OBJECTIVE: To investigate the clinical effect of a 0.1% cetylpyridinium
      chloride(CPC) rinse on the treatment of gingivitis and periodontitis. METHODS: A
      multicenter, randomized, parallel group trial was conducted. The eligible
      patients were divided randomly into two groups. Subjects were assessed at the
      beginning and the end of a two-week period during which they rinsed with 0.1% CPC
      or complex hibitane in addition to their usual oral hygiene procedures. The
      variation of PLI, SBI, GI, PD, pain, halitosis and adverse effects were observed
      before and after investigation. RESULTS: After 14 days of treatment, in the CPC
      group, the decreasing rate of PLI was 63.0%, the effective rate for gingivitis
      and periodontitis were 83.3%, 36.7% respectively, while those periodontal indices
      of control group were 49.5%, 50% and 16.7%. After statistical analysis, the CPC
      group had significantly higher effective rates on gingivitis than the hibitane
      group (P < 0.01), at the same time, the effective rate was significantly
      different between two groups on periodontitis (P < 0.05). CONCLUSION: The use of
      0.1% CPC rinse is effective in treating periodontal diseases.

PMID- 14966579
TI  - [Clinical effects of three systems of dental implants].
AB  - OBJECTIVE: To evaluate the clinical value of dental implants including Branemark,
      Steri-oss and BLB systems. METHODS: The total 384 implants of different materials
      and shapes were inserted normally. According to the Chinese standard of dental
      implantation, the success rates of three types were compared. RESULTS: By
      following-up from one year to five years, the success rates of all implants were
      above 97%. CONCLUSION: The success rates of routine implants were mainly
      associated with indication, case selection, operation, rehabilitation and
      patients maintenance.

PMID- 14966580
TI  - [The analysis of masticatory efficiency after maxillofacial prosthetic treatment
      for unilateral maxillary defect].
AB  - OBJECTIVE: To evaluate the clinic results of maxillofacial prosthetic treatment
      for unilateral maxillary defect. METHODS: Masticatory efficiency was tested
      before and after maxillofacial prosthetic treatment for unilateral maxillary
      defect. RESULTS: There was significant difference between one week, one month,
      three months after treatment and before treatment(F = 0.635, P = 0.002).
      Masticatory efficiency was increased by 59.98% after one month. CONCLUSION:
      Maxillofacial prosthetic treatment can significantly increase the masticatory
      efficiency of unilateral maxillary defect. It remains stable one month later.

PMID- 14966581
TI  - [An epidemiological survey on fusion of deciduous teeth of 4286 kindergarten
      children in Shenyang city].
AB  - OBJECTIVE: To clarify the occurrence and distribution of the fusion of deciduous
      teeth in Shenyang. METHODS: By using cross-sectional study, 4286 children were
      examined, who aged from 2 to 6 years in 37 kindergartens. RESULTS: Of 4286
      children investigated, fusion of the deciduous teeth were detected in 65 children
      (1.52 percent) without sex predilection. The fused teeth typically occurred
      unilaterally (68.75 percent), and mainly located in the anterior region, more
      frequently in the mandibular (91.25 percent) than that in the maxillary arch. 12
      cases were bilaterally symmetrical (18.46 percent). Two rare cases were found
      with fused teeth, one occurred in central incisor, lateral incisor and canine,
      the other occurred between two molars with two incisors fused in the same side.
      Fused teeth in two cases had caries. CONCLUSION: The occurrence of the fused
      teeth may cause some complications. Pediatric dentists should pay attention to
      the fused teeth occurred in preschool children.

PMID- 14966582
TI  - [Expression of matrix metalloproteinases and tissue inhibitor of
      metalloproteinase in ameloblastoma].
AB  - OBJECTIVE: To study the expression of matrix metalloproteinase(MMP) and tissue
      inhibitor of metalloproteinase (TIMP) in ameloblastoma (AB) and to determine the
      relationship between biological behavior of AB and clinical pathology. METHODS:
      The specimens of 43 cases of AB, 10 cases of odontogenic keratocyst (OKC), 8
      cases of normal oral mucosa were examined by streptavidin-biotin method. RESULTS:
      In 8 cases of normal oral epithelial, MMP-2 was negative or weak positive. In
      OKC, MMP-2 was extensively positive in stratum spinosum of 2 cases, and weekly or
      negative in stratum basale. MMP-2 was strongly expressed in the central and
      peripheral cells of the tumor islands in 28 cases of AB. There were difference
      among these three groups (P < 0.001). Comparing AB with normal oral mucosa and
      OKC, there was significant difference (P < 0.05). MMP was positive expressed in
      cells of stroma. The positively rate and intensity increased as AB recurrence and
      transformed malignantly, but were not associated with age, sex, pathological type
      and location. TIMP-1 was weakly or not expressed in normal oral mucosa, stoma,
      OKC and AB. CONCLUSIONS: The high expression of MMP-2 and MMP-9 is related to the
      biological behavior of AB. Imbalances of the expression of MMP-2 and MMP-9
      protein maybe be one of the facts of the invasion of AB. The MMPs activation
      produced by stromal cells may be also be related to the invasion of AB.

PMID- 14966583
TI  - [Establishment and drug-resistance gene expression of cisplatin-resistant cell
      line Tca8113/CDDP].
AB  - OBJECTIVE: To establish a CDDP-resistant cell line from human tongue squamous
      cell carcinoma cell line Tca8113 and to compare the drug-resistance gene
      expression between them. METHODS: The concentration of CDDP added to Tca8113
      cells was increased stepwise to induce the CDDP-resistance. The index of drug
      resistance was estimated by MTT assay. The expression of MDR-1, MRP, GST-pi and
      Bcl-2 was measured by RT-PCR optical density OD. RESULTS: The CDDP-resistant cell
      line, Tca8113/CDDP was established, whose drug-resistance index was 9.2. The
      expression of MDR-1, MRP, cyclin D1 and Bcl-2 increased respectively. CONCLUSION:
      The expression of drug-resistance gene in Tca8113/CDDP was significantly higher
      than that in Tca8113.

PMID- 14966584
TI  - [Evaluation of low level laser therapy in temporo-mandibular joint disorders].

PMID- 14966585
TI  - [Effects of bovine plasma fibronectin on the proliferation of rat osteoblast in
      vitro].
AB  - OBJECTIVE: To investigate the effects of bovine plasma fibronectin on the
      proliferation of rat osteoblast in vitro. METHODS: Cell cultured. AlamarBlue were
      used to determine the effect of various concentration of bovine plasma
      fibronectin on the proliferation of rat osteoblast in vitro. RESULTS: Fibronectin
      can stimulate the proliferation of rat osteoblasts. Statistically significant
      difference was detected at dose of 40 micrograms/ml (P < 0.05) and dose of 50
      micrograms/ml (P < 0.01). CONCLUSIONS: Certain concentration of bovine plasma
      fibronectin can stimulate the proliferation of rat osteoblast in vitro.

PMID- 14966586
TI  - [Cell behavior of periodontal ligament cells cultured on commercially pure
      titanium].
AB  - OBJECTIVE: To study the cell behavior of periodontal ligament cells (PDLCs)
      cultured on commercially pure titanium (cpTi) by cell morphology, cell counting
      and osteoclin (OC) immunofluorescent staining. METHODS: 1 x 10(5)/ml PDLCs in 2
      ml culture medium were seeded on cpTi discs fixed in 24-well culture plates.
      Morphological study of cell attachment was observed by scanning electron
      microscope (SEM) and fluorescence microscopy. Cell adhesion was analyzed by MTT
      at 0.5, 1, 2, 4 hours respectively. OC was directly observed by immunofluorescent
      staining. RESULTS: PDLCs could attach and spread on cpTi discs. SEM showed that
      PDLCs had pseudopod-like protuberance. PDLCs showed different attaching phase and
      reached saturation in cell number at the early stage. The cells and ECM could
      express OC 7 days later. CONCLUSION: PDLCs show a regular, dynamic pattern in
      early stage and they can keep proliferating and differentiating on CpTi in vitro.
      It was indicated that the biological function of PDLCs around dental implant
      should be reconsidered.

PMID- 14966587
TI  - [Microvessel density and expression of vascular endothelial growth factor in
      adenoid cystic carcinoma of salivary gland].
AB  - OBJECTIVE: To discern whether the microvessel density (MVD) and the expression of
      vascular endothelial growth factor (VEGF) could be prognostic indicators for the
      metastasis and survival of patients with SACC after radical surgery. METHODS:
      After the follow-up of 31 primary patients with SACC treated with radical
      surgeries for at least 60 months, the paraffin-bedded sections of the those
      patients were stained immunohistochemically with anti-CD34-McAb and anti-VEGF
      McAb, respectively. Subsequently, two pathologists double-blindly evaluated the
      sections stained with anti-CD34-McAb to determine the MVD values individually, as
      well as, measured the sections stained with the ani-VEGF-McAb to determine the OD
      values. Consequently the data were analyzed with the statistic software package
      detailed. RESULTS: The univariate statistical analysis showed that the
      pathological types of SACC, the TNM stages, MVD and OD values were all
      statistically significant variables for the survival of the patients with SACC (P
      = 0.047, 0.000, 0.000, 0.024). Furthermore, among those reliable variables, only
      MVD was more significant in the Cox proportional hazard model for the
      multivariate analyses (P = 0.000). The MVD values were statistically
      significantly higher, in the group with either death, or metastasis, or tumor
      relapse, or worse pathological types, or advanced TNM stages, than their
      counterparts respectively(P = 0.029, 0.045, 0.019, 0.031, 0.00). On the other
      hand, the OD values were also statistically significantly higher, in the group
      with either death, or worse pathological types, or advanced TNM stages, than
      their counterparts respectively(P = 0.037, 0.013, 0.014). The results of Fisher
      exact test showed that the incidence of distant metastasis differed statistically
      significantly between the subgroups divided with the median of the MVD values (P
      = 0.032). The stepwise linear regression equation showed that the MVD value
      correlated positively with the OD value (P = 0.029). CONCLUSIONS: The MVD value
      and the expression level of VEGF all have statistically significant correlations
      with the survival of the patients with SACC, moreover, the MVD value is more
      significant as a prognostic indicator. The MVD value could also be a prognostic
      indicator for the incidence of the distant metastasis of patients with SACC. The
      over-expression of VEGF in SACC might contribute to the MVD values increasing.

PMID- 14966588
TI  - [The effect of adriamycin to the trigeminal ganglion following injection into the
      rabbits infraorbital nerve].
AB  - OBJECTIVE: To observe the effect of adriamycin to suborbital nerve and trigeminal
      ganglion in the rabbits. METHODS: 20 microliters adriamycin with different
      concentrations of 0.5%, 1.0%, 3.0%, 5.0% were injected into the suborbital nerve
      trunks, respectively. The changes of compound action potential (CAP),
      autofluorescence and histological feature in suborbital nerve and trigeminal
      ganglion were observed. RESULTS: With suitable adriamycin concentration,
      autofluorescence could be observed at 10 hours after injection, and reached
      highest at 20 hours. CAP amplitudes reduced at 10 h, disappeared after 20 h and
      could not be stimulated after 6 months. Morphological change began after 15 d and
      became obvious with time going. The regeneration of neurons was not observed 6
      months after injection, while the tissue surrounding the necrotic nerve and
      ganglion cells were normal morphologically. CONCLUSIONS: Adriamycin can damage
      axons and corresponding ganglion cells by the way of suicide transport
      permanently, but the damage was highly selective and self-limited.

PMID- 14966589
TI  - [Application of primacaine in operative dentistry: analysis of clinical results].

PMID- 14966590
TI  - [Comparison on shear bond strength of Edgewise brackets bonding with three
      orthodontic adhesives against salivary contamination].
AB  - OBJECTIVE: To compare the shear bond strength and ARI score of Edgewise brackets
      bonding with three adhesives under moist and dry conditions after salivary
      contamination. METHODS: Sixty extracted human premolars were randomly and equally
      divided into 3 groups. Edgewise brackets were bonded directly with composite
      resin, super bond C&B and single component adhesive under moist and dry
      conditions after salivary contamination. The shear bond strength and ARI score
      were measured and recorded. RESULTS: The shear bond strength of Edgewise brackets
      bonding with composite resin and single component adhesive under moist condition
      after salivary contamination decreased significantly and it can't meet the
      requirement of orthodontic therapy (6-8 MPa) while that under dry condition can.
      Super bond C&B can meet the requirement of orthodontic therapy on both
      conditions. CONCLUSION: Super bond C&B can be used under both moist and dry
      conditions after salivary contamination. Composite resin and single component
      adhesive can only be used under dry condition after salivary contamination.

PMID- 14966591
TI  - Study on the correlation of cytokine gene polymorphism with chronic
      periodontitis.
AB  - OBJECTIVE: To study the correlation of gene polymorphism IL-1B +3953 and TNF-A
      308 and the genetic susceptibility to moderate-to-advanced adult
      periodontitis(AP). METHODS: PCR-RFLP technique was used to identify IL-1B +3953
      and TNF-A-308 genotype. Multivariate logistic regression model was utilized to
      assess the relationship of IL-1B +3953 and TNF-A-308 positive genotype to disease
      status while adjusting for other potential confounders. RESULTS: The frequency of
      IL-1B +3953 (28.23%) and TNF-A-308 (29.03%) allele 2 positive genotype in
      patients with moderate-to-advanced AP showed a statistically significant increase
      compared to the control group frequency (13.95% IL-1B +3953 and 11.05% TNF-A
      308), and the difference was of much significance (P < 0.01 in both group).
      Multivariate logistic regression analysis showed that IL-1B +3953 and TNF-A-308
      allele 2 positive genotype may increase the odds of having moderate-to-advanced
      AP and the IL-1B +3953 (P < 0.05) and TNF-A-308 (P < 0.01) allele 2 positive
      genotype was of statistical significance. CONCLUSIONS: IL-1B +3953 and TNF-A-308
      allele 2 positive genotype have closer correlation with moderate-to-advanced AP.

PMID- 14966592
TI  - [Causes and prevention of "black line" in porcelain-fused-to-metal crown
      margins].

PMID- 14966593
TI  - [Retention design of the superstructure in implant-supported overdentures].

PMID- 14966594
TI  - [Miniplate internal fixation of multifractures in zygoma and zygomatic arch
      through semicoronoid incision].

PMID- 14966595
TI  - [The effect of scaling on periodontal health of orthodontic children].

PMID- 14966596
TI  - [The clinical effect of one type of paste material on gingival retraction].

PMID- 14966597
TI  - [Clinical study on locally widening too limited space of incisors before PRF
      bridge].

PMID- 14966598
TI  - [Clinical analysis of extraction of 36 cases with embedded supernumerary teeth in
      the maxilla].

PMID- 14966599
TI  - [The clinic observation of lag screw internal fixation in the treatment of
      condyloid process fracture of the mandible].

PMID- 14966600
TI  - [Combine orthodontic treatment with implants on malocclusion in the permanent
      dentition with missing teeth].

PMID- 14966601
TI  - [Long term follow-up results of Chinese prescription "Shen Yang" in the combined
      and sequential treatment of oral squamous cell carcinoma].
AB  - OBJECTIVE: To evaluate the long term therapeutic effect of Chinese prescription
      "Shen Yang" in the combined and sequential therapy for oral squamous cell
      carcinoma cases. METHODS: There are 238 cases with oral squamous cell carcinoma.
      They were divided into two groups randomly as "Shen Yang" experiment group and
      control group (placebo). 25 cases were precluded from the experiment group. 17 of
      them were due to unexperiment of taking "Shen Yang" within three months. 8 cases
      were lost of follow-up. 213 patients were included in this study. Among them, 104
      cases in experiment group, and 109 cases in control one. Patients in both groups
      were followed-up for 5-10 years. Their life-curve was calculated by means of
      Logrank method. RESULTS: The survival rate of "Shen Yang" group was improved by
      8.46%, 9.26%, 9.04% and 8.57% for 3-year, 5-year, 8-year and 10-year survival
      rates. But the differences between the two groups were not statistically
      significant (P=0.1936, P>0.05). CONCLUSION: Chinese prescription of "Shen Yang"
      had a tendency to improve the survival rate for oral squamous cell carcinoma
      patients.

PMID- 14966602
TI  - [The diagnostic value of computed tomography and magnetic resonance imaging in
      squamous cell carcinoma of tongue: a comparative study].
AB  - OBJECTIVE: To compare the diagnostic values of CT and MRI in estimating the
      thickness of lingual squamous cell carcinoma, and evaluate the relationship
      between the thickness of tongue carcinoma on MRI and lymph node metastasis rate.
      METHODS: 23 patients with squamous cell carcinoma of tongue. All the 23 patients
      were examined with CT and MRI. The actual thickness of tongue carcinoma was
      measured after surgery. RESULTS: (1)There was a significant difference between
      the actual thickness of tongue carcinoma and the thickness shown on CT (P<0.05),
      and no significant difference between the actual thickness of tongue carcinoma
      and the thickness shown on MRI (P>0.05). (2)Lymph node metastasis rate was 84.6%
      when the thickness of tongue carcinoma on MRI was greater than or equal to 2cm,
      and 10.0% when the thickness of tongue carcinoma on MRI was less than 2cm. There
      was a significant difference between the two groups of patients. (3)MRI can show
      the area of the tongue carcinoma clearly without enhancement. It has better
      resolution than CT. CONCLUSION: (1)MRI is better than CT in estimating the
      thickness of tongue carcinoma. (2)Thickness of tongue carcinoma on MRI could be
      employed to estimate the possibility of lymph node metastasis.(3)MRI should be
      the first choice in the diagnosis of tongue carcinoma.

PMID- 14966603
TI  - [Clinical study on the causes and treatment of endodontic interappointment
      emergencies].
AB  - OBJECTIVE: To investigate the causes and the treatment of endodontic
      interappointment emergencies. METHODS: An analysis were made for 55 teeth with
      endodontic interappointment emergencies. The root canals were sealed with
      dexamethasone and metronidazole,and filled with Vitapex add gutta-percha point
      after one week. An evaluation of curative effect was made after following up one
      year. RESULTS: The total incidence of endodontic interappointment emergencies was
      12.59%(55/437). There was significant difference between pulpitis and pulp
      necrosis or apicitis(P<0.01). There was significant difference between anterior
      teeth and posterior teeth (P<0.01). The success rate was 92.7% after following up
      one year. CONCLUSION: The cause of endodontic interappointment emergencies was
      related to pulp status and tooth location,etc. The treatment that sealed the root
      canals with dexamethasone and metronidazole and filled with Vitapex add gutta
      percha point is of availability.

PMID- 14966604
TI  - [The correlation between tooth pain and bioactivators changes in gingival
      crevicular fluid after applying orthodontic stress].
AB  - OBJECTIVE: To investigate the changes of tooth pain in patients with orthodontic
      tooth movement, to study the changes of bioactivators in GCF in patients with
      orthodontic tooth movement, and explore the correlation between pain and
      bioactivators in orthodontic patients. METHODS: 50 patients were included, each
      having one treatment tooth and one contralateral control tooth. The levels of
      PGE(2), P substances, IL-6 and GM-CSF in GCF of upper lateral incisor were
      investigated before activation and at 12th hour, 24th hour, 48th hour and 72th
      hour after the applying labial orthodontic force, by using highly sensitive
      radioimmunassay. To record the changes of pain in orthodontic patients at 12th
      hour, 24th hour,48th hour and 72th hour after applying stress. RESULTS: At
      experimental sides, total amount of GCF PGE(2), P substances(SP), IL-6 and GM-CSF
      levels was significantly elevated compared with that before activation. The
      concentration of PGE(2) and SP in GCF increased significantly and reached peak
      point at 24th hour in patients, while the levels of IL-6 and GM-CSF in GCF
      remained at higher baseline through the experiment. There was an rhythm change of
      periodontal pain during orthodontic tooth movement. CONCLUSION: There was an
      rhythm changes of pain after stress in patients with orthodontic tooth movement,
      and the rhythm pain was correlated to the changes of some activator such as P
      substances and PGE(2) in periodontal ligament.

PMID- 14966605
TI  - [A clinical study of the changes of condylar position in class division 2 deep
      bite patients after orthodontic treatment].
AB  - OBJECTIVE: To observe the effects of orthodontic treatment on the changes of
      condylar position in Class division 2 deep-bite patients. METHODS: 11 patients
      with Class division 2 deep-bite malocclusion were orthodontically treated, the
      changes of condylar position were evaluated by means of 3D-CT and Sam-diagnostic
      articulator. RESULTS: With the increase of inclination of upper incisors and
      opening bite, there were statistically significant changes of condylar
      longitudinal distance and condylar height in both sides, and retruded contact
      position-intercuspal position(RCP-ICP) discrepancy was significantly reduced.
      CONCLUSION: The condylar position in division 2 deep-bite patients could be
      orthodontically changed, moving anterior-inferiorly and approaching RCP.

PMID- 14966606
TI  - [The fluctuation of anterior teeth colouration during the period of growth
      puberty in children and adolescents].
AB  - OBJECTIVE: This study was designed to examine the fluctuation tendency of the
      anterior teeth coloration during the period of growth puberty. METHODS: One
      hundred children with average age of 13.3 years, and 100 adolescents with average
      age of 23.4 years were divided into two groups. The upper left incisors were
      selected for color matching using computerized spectrophotometery system (Shade
      eye, Shofu). The measurements depicting color properties, including hue, value
      and chroma were quantitatively analyzed. Statistical evaluation was conducted for
      the comparison of the color measurements between the two groups. RESULTS: The
      following trends were indicated during the period of growth puberty: (1)The hue
      of the coloration changed from redness into mixture of redness and grayness.
      (2)The magnitude of value of the coloration was in decline. (3)The intensity of
      chroma increased significantly. CONCLUSIONS: The teeth coloration fluctuates
      within the period spanning the initial and final stages of growth puberty,
      characterized by a decrease in hue and value and an increase in chroma.

PMID- 14966607
TI  - [Clinical effect of Sonicare electric toothbrush in treating gingivitis].
AB  - OBJECTIVE: To observe the clinical effect of Sonicare toothbrush in treating
      gingivitis by means of using Sonicare toothbrush in both healthy group and
      gingivitis group. METHODS: 50 medical students aged 18 to 25 years old were
      selected. At first,The gingival Index(GI) was examined and they were divided into
      2 different groups. The students were instructed to use the Sonicare toothbrush,
      demanding them to brush teeth 2 times one day and 2 minutes each time. One month
      later,the GI were reexamined. RESULTS: After one-month period of using Sonicare
      toothbrush, the GI decreased significantly in both groups and the difference was
      statistically significant. CONCLUSION: Sonicare toothbrush can remove debris and
      improve gingival health. It is effective tool for family oral care.

PMID- 14966608
TI  - [Preliminary analysis of gene expression profiles in oral cancer with microarray
      technique].
AB  - OBJECTIVE: To study the difference in gene expression between oral squamous cell
      carcinoma tissue and their surrounding normal tissue by microarray so as to
      investigate the preliminary mechanism of pathogenesis of oral cancer. METHODS:
      The tissues from 5 patients with oral squamous cell carcinoma tissue and their
      surrounding normal tissue from the same patients were analyzed by cDNA microarray
      technology(including 4124 genes). Total RNAs were isolated from two tissues, and
      then were reversely transcribed to cDNAs with the incorporations of fluorescent
      dUTP,for preparing the hybridization probes. The mixed probes were then
      hybridized to the cDNA microarray. After high-stringent washing, the cDNA
      microarray was scanned for the fluorescent signals and showed the differences
      between the two tissues. Bioinformatical analysis of those genes had been
      performed. RESULTS: Among the 4124 target genes, there were 37(0.89%)genes whose
      expression levels differed between the carcinoma and their surrounding normal
      tissues in all 5 cases. Bioinformatical analysis of those genes suggested that
      they may be related to the multistep process of carcinogenesis. CONCLUSION: cDNA
      microarray technique can simultaneously screen the different expressions of genes
      from 2 different kinds of tissue. Further analysis of the obtained genes will
      help to understand the molecular mechanism of malignant carcinoma.

PMID- 14966609
TI  - [Developing a straight wire bracket placement gauge].
AB  - OBJECTIVE: To develop a new straight wire bracket placement gauge, providing
      measurement instrument for it's accurate position. Methods The gauge was made of
      3.0 mm x 6.0 mm stainless steel, after being curved in certain form, made by
      machine process and cleaned through removing tough and polishing. The bracket
      placement gauge is divided into three parts: the middle straight stem, the curve
      head and the measurement head. It was 146 mm long, the angle between straight
      stem and curve was 145 degrees,the angle between the curve and measurement head
      was 105 degrees.The measurement head was made of occlusion placement item and
      slot placement item. The occlusion placement item was 10 mm long and 2 mm thick.
      The slot placement item was 2 mm long and 0.4 mm thick. This suit of gauge had 7
      pieces, the measurement scope was 2.5 mm-5.5 mm which reflected the different
      vertical distances from occlusion edge to the middle point of slot. RESULTS: This
      gauge can determine the vertical position of bracket. CONCLUSION: The gauge
      improve the accuracy with individual straight wire bracket position table.

PMID- 14966610
TI  - [Research on histologic changes of periodontal tissue, testification of TNF-alpha
      and their relationship in diabetics rats].
AB  - OBJECTIVE: The histologic and TNF-alpha changes of the experimental periodontitis
      were studied in diabetic rat model in different periods. The mechanism of the
      occurring and developing of periodontitis was probed on the aspect of cytology.
      METHODS: The diabetic rat models were established by injecting streptozotocin
      into its abdomen. The local stimulation was caused by tiring silk thread to
      teeth. The histologic changes of periodontium were observed at 6,9,and 12 weeks.
      The level of TNF-alpha was testified using immunohistochemistry method at 12
      weeks. RESULTS: Periodontitis occurred in diabetic rats earlier than in non
      diabetic ones. The destructions were more severe and more widely in diabetic rats
      than in non-diabetic ones. The level of TNF-alpha was higher in the experimental
      periodontium of diabetic rats than those non-diabetics. CONCLUSIONS: Diabetes
      mellitus has an accelerating effect on occurring and developing of periodontitis.
      When with diabetes, more cytokines were released, and cause the unbalance of ruin
      and repair and result in the enhancing of periodontitis.

PMID- 14966611
TI  - [Comparison of the antibacterial activity on oral pathogens among six types of
      nano-silver base inorganic antibacterial agents].
AB  - OBJECTIVE: To Compare the antibacterial activity on oral pathogens among six
      types of nano-silver base inorganic antibacterial agents. METHODS: The oral
      pathogens selected were Streptococcus mutans(ATCC6715),Lactobacillus
      (ATCC4356),Actinomyces viscosus (ATCC19246), Candida Albicans (ATCC76615),
      Staphylococcus aureus (ATCC25923), Escherichia coli (ATCCC25922). Minimal
      bactericidal concentration (MBC) was determined by Liquid dilution method.
      RESULTS: Nano-silver base inorganic antibacterial agents had fine bactericidal
      activity against oral pathogens. The general antibacterial activity of six types
      were nearly equal. CONCLUSION: It is possible that nano-silver base inorganic
      antibacterial agents can be used in dental antibacterial materials.

PMID- 14966612
TI  - [Analysis of the effect on the stress of root canal wall by vertical and lateral
      condensation procedures].
AB  - OBJECTIVE: To analyse the stress variations of root canal wall that resulted from
      vertical and lateral condensation. METHODS: On the basis of the finite-element
      model of the mandibular first molar that modified by step-back technique, mesial
      buccal root canal was chosen as tested root canal and simulated the procedure of
      vertical and lateral condensation. The maximal stress of root canal wall and its
      position were calculated by special software upon different loading condition.
      RESULTS: Stress of root canal wall caused by vertical condensation was higher
      than that by lateral condensation on the same loading condition. Maximal stress
      of vertical condensation was located on loading section and one of lateral
      condensation was located on coronal and middle 1/3 of root. The lower the
      position that was loaded, the higher the stress of wall of root canal.
      CONCLUSION: Lateral condensation will not bring on vertical root fracture
      directly,but over-force and improper operation are both dangerous that gives rise
      to vertical root fracture with whichever method.

PMID- 14966613
TI  - [Biocompatibility of chitosan-carboxymethylchitosan as membrane for periodontal
      guided tissue regeneration].
AB  - OBJECTIVE: To investigate the biocompatibility of chitosan-carboxymethylchitosan
      as membrane for periodontal guided tissue regeneration (GTR). METHODS: Chitosan
      carboxymethylchitosan blending membrane was prepared by freeze-drying and tests
      including cytotoxicity test, inserting the membrane into the rabbits, muscles,
      were employed to investigate its biocompatibility. RESULTS: Chitosan
      carboxymethylchitosan blending membrane showed no toxicity. In early period after
      the insertion of the membrane, inflammatory processes with macrophages were
      observed, but the processes reduced with the membrane degradation. CONCLUSION:
      Chitosan-carboxymethylchitosan blending membrane has desirable biocompatibility.

PMID- 14966614
TI  - [Expression of estrogen and progesterone receptors in the gingival tissues of
      female patients with moderate and advanced periodontitis].
AB  - OBJECTIVE: The purpose of this study was to compare the difference of sexual
      hormone receptors' expression and distribution in the gingival tissues between
      periodontitis patients and normal females and to provide the theoretical facts
      for the clarification of periodontitis's pathogenesis. METHODS: The test group
      was 34 samples and normal control group was 30 samples. The test group and the
      normal control group were divided into 3 subgroups separately according to age.
      All specimens were studied for ER and PR proteins' expression using
      immunohistochemical techniques (Envision) uniformly, and observed by light
      microscope. RESULTS: ER and PR proteins located in cytoplasm or nuclear. ER and
      PR proteins' stainings occurred in the epithelium, the distribution of them had
      no regularity and staining intensity varied. The positive rates of ER and PR in
      the gingival tissues of normal female were low. The positive rate of ER in the
      gingival tissues of female with periodontitis soared apparently (P<0.01), but the
      positive rate of PR changed little (P>0.05). CONCLUSION: The expression of ER in
      the gingival tissues might have relation to periodontitis of females. Besides
      acting indirectly on the gingival tissues, estrogen could affect the gingival
      tissues directly by ER; progesterone might have indirect effects on gingival
      tissues.

PMID- 14966615
TI  - [The advancements in correction of adult transverse maxillary deficiency].

PMID- 14966616
TI  - [The relationship between occlusion and masseter muscles].

PMID- 14966617
TI  - [Clinical evaluation of zinc oxide eugenol and Vitapex as root canal filling
      materials in primary teeth].

PMID- 14966618
TI  - [Prospective comparison of arthrocentesis and pressured injection for anterior
      disc displacement without reduction of temporomandibular joint].

PMID- 14966619
TI  - [Lateral branch root of maxillary lateral incisor: report of one case].

PMID- 14966620
TI  - [The study on treatment of anterior crossbite cases in mixed dentition applying
      FR-III combind with maxillary removable appliance].

PMID- 14966621
TI  - [Changes of pulp activities caused by light cured composite composite resin in 52
      cases].

PMID- 14966622
TI  - [Clinical analysis of the causes of recurrence of trigeminal neuralgia after
      operation: report of 109 cases].

PMID- 14966623
TI  - [The treatment of teeth split and analysis of causes for failure].

PMID- 14966624
TI  - [Preliminary observation after bonding and replantation of vertical fractured
      posterior teeth].

PMID- 14966625
TI  - [Management of root canal reamer fell into the digestive tract].

PMID- 14966626
TI  - [Radiological location and surgical operation route of the embedded supernumerary
      teeth in maxilla].

PMID- 14966627
TI  - [Use of block anaesthesia of the mandibular nerve in parotidectomy].

PMID- 14966628
TI  - [Clinical results of CCQ paste for treatment of chronic apicitis].

PMID- 14966629
TI  - [Application of III-type bio-modulator in the reversed horizontal overbite of the
      deciduous dentition and mixed dentition].

PMID- 14966630
TI  - [Fluoride concentration in saliva after use of fluoride varnish].
AB  - OBJECTIVE: The purpose of this vivo study was to compare fluoride concentration
      in saliva of patients treated with fluoride varnish and fluoride solution.
      METHODS: 20 5-year-old children were selected and divided into fluoride varnish
      and fluoride solution groups. The samples of unstimulated whole saliva were
      collected at base-line before and after 0.25h,0.5h,1h,2h,6h,12h,24h treatment
      with fluoride varnish and fluoride solution. Saliva fluoride concentrations were
      measured using an ion-specific electrode. RESULTS: After 0.25h,0.5h,1h,2h,6h
      treatment with fluoride varnish, the values of salivary fluoride concentration
      were higher than baseline,the values of fluoride varnish group were higher than
      those in fluoride solution group after 0.5h to 6h. CONCLUSION: Compared with
      fluoride solution, fluoride varnish maintained a longer time of high salivary
      fluoride concentration.

PMID- 14966631
TI  - [The observation of the effect of metronidazole-chlorhexidine solution on
      treatment of periapical periodontitis].
AB  - OBJECTIVE: To observe the effect of metronidazole-chlorhexidine solution on
      treatment of periapical periodontitis. METHODS: 202 teeth suffering from chronic
      periapical periodontitis were selected and divided into two groups. One group
      including 102 teeth were treated with metronidazole-chlorhexidine solution.
      Another group including 100 teeth were treated with formocresol. The acute
      symptoms during root canal therapy were observed. 164 teeth suffering from acute
      periapical periodontitis were also selected and divided into two groups. One
      group including 80 teeth were treated with metronidazole-chlorhexidine solution.
      Another group including 84 teeth were treated as the above except the pulp
      chamber keeping open. The other 44 teeth, in which purulence also presented in
      the root canal after treated with formocresol and iodoform for three times or
      more, were treated with metronidazole-chlorhexidine solution. The presence of
      purulence was evaluated. RESULTS: There are significant differences between the
      two groups of chronic and acute periapical periodontitis(P<0.05). The effective
      rate was 97.6% after changed to metronidazole-chlorhexidine solution treatment.
      CONCLUSION: Good treatment effect could be achieved by using metronidazole
      chlorhexidine solution as the root canal cleaning and disinfection agent.

PMID- 14966632
TI  - [Subjective evaluation of acoustic changes before and after restoration with
      complete denture].
AB  - OBJECTIVE: To evaluate clinic adaptive effect of speech articulation of patients
      before and after restoration with complete denture. METHODS: Before and after
      patient's restoration at the beginning and then at 1 week, 2 weeks, 4 weeks and 8
      weeks, the patient's self-judgement and the measurement of Chinese
      intelligibility by speech pathologist were used to analyse the regularity of
      speech articulation of edentulous patients restored with complete denture.
      RESULTS: At the beginning, the patients in two groups all felt uncomfortable of
      using denture. After one week, patients using metal base denture adapted well,
      but patients using plastic base denture needed 2 weeks to adapt. The data of
      Chinese intelligibility showed significant difference between two groups after
      using denture 1 week (P<0.05). In metal base group, there was significant
      difference before and after using denture a week (P<0.01). The plastic base group
      showed this change after two weeks. CONCLUSION: Patient's phonetic function
      recovered quickly when the thickness of the base reduced and palatal rugae of the
      denture base restored. The chinese intelligibility of them was better.

PMID- 14966633
TI  - [A clinical study of doxycycline slow-release gel on periodontitis chemotherapy].
AB  - OBJECTIVE: To observe the effect of Doxycycline slow-release on periodontitis
      therapy. METHODS: 30 patients with chronic periodontitis were chosen and divided
      into 2 groups randomly,these cases were given Doxycycline slow-release and
      Zinciodati Comp solution. PLI,GI,SBI,PD,AL,MD and clinical symptoms were observed
      before and after taking drug. RESULTS: The indose of PLI,GI,SBI,PD,AL,MD were
      decreased significantly after the use of Doxycycline slow-release gel
      (P<0.05),the effects of the Doxycycline was better than Zinciodati Comp solution
      (P<0.01), no adverse drug side effects were found during trial. CONCLUSION: The
      use of Doxycycline slow-release gel is one of the safe and effective chemotherapy
      on periodontitis.

PMID- 14966634
TI  - [Observation of the clinical effect on the treatment of traumatic intrusion of
      upper anterior teeth using orthodontic method].
AB  - OBJECTIVE: To observe the clinical effect on the treatment of traumatic intrusion
      of upper anterior teeth using orthodontic extrusion combined with fixation.
      METHODS: 24 cases, 27 teeth included, were treated by means of orthodontic
      extrusion combined with composite-resin split fixation. The clinical effect of 2
      year-period was recorded. RESULTS: After the treatment of 27 selected teeth (16
      immature teeth,11 mature teeth),11 teeth achieved the standard of success,16
      teeth achieved the standard of efficiency, none of them was failing. CONCLUSION:
      Orthodontic extrusion combined with composite-resin split fixation is an active
      and atraumatic method in the treatment of traumatic intrusion of upper anterior
      teeth, and the effect is ideal.

PMID- 14966635
TI  - [The feasibility and reliability of Pancherz's analysis in evaluating the
      treatment effects of bite-jumping on skeletal class II malocclusion].
AB  - OBJECTIVE: This study was designed to conduct an in-depth evaluation on
      Pancherz's analysis. METHODS: A typical Class II case with bite-jumping therapy
      was selected for the whole process of Pancherz's Analysis. The skeletal growth
      modification and dental compensation were examined and portioned for their
      respective contribution to the correction of excessive overjet and Class II molar
      relationship. RESULTS: The following traits and properties of Pancherz's analysis
      were found: (1) A fixed reference system characterized by SN and OLp was
      established which led to an accurate detection of the moving objects. (2)
      Skeletal and dental changes were separated for evaluation, which resulted in a
      true assessment of the bite-jumping on growth pattern modification.(3) A
      segmental examination for dental changes indicated the magnitude of skeletal
      modification. Conclusion Pancherz's analysis is a feasible and reliable
      evaluation system which could reflect with accuracy the skeletal and dental
      effects caused by bite-jumping therapy.

PMID- 14966636
TI  - [Analysis of short-term pain occurrence applying different materials for root
      canal therapy].
AB  - OBJECTIVE: The aim of this study is to compare the occurrence of pain applying
      different materials of root canal therapy in vital teeth. METHODS: 288 vital
      teeth were divided into 4 groups, Cortisomol sealer+gutta-percha and
      Vitapex+gutta-percha were used respectively in 2 groups of one time method; while
      Cortisomol sealer+gutta-percha and Vitapex+gutta-percha were used after 24-48
      hours drainage in the other 2 groups. The occurrence of pain after 1 week was
      recorded. RESULTS: In all treated teeth,the occurrence rate of self-healing pain
      after root canal therapy was 22.6%, the occurrence rate of non-self-healing was
      2.08%; in the groups of one time method,the occurrence rate of pain using
      Cortisomol was lower than the group using Vitapex with significant
      difference(P<0.01); while in the groups of root canal filling after drainage,the
      occurrence of self-healing pain in the group using Cortisomol was lower than the
      group of using Vitapex without significant difference(P>0.05);the pain occurred
      within 72 hours in most of the teeth. CONCLUSION: Root canal treatment applying
      Cortisomol sealer+gutta-percha can decrease the rate of pain occurrence after
      root canal filling.

PMID- 14966637
TI  - [An analysis of the state of teeth of 961 elderly cadres in Shenyang City].
AB  - OBJECTIVE: To assess the current state of teeth in elderly cadres in Shenyang
      City. METHODS: According to the standards of the 2nd national oral health
      sampling survey, 961 elderly cadres, above 60 years old, were examined. The
      results were processed using SPSS. RESULTS: 67.12% had dental caries and among
      them 33.18% were completely treated. The mean numbers of decayed and filled teeth
      in persons with caries become higher with the increase of ages (P<0.05). 80.65%
      of individuals had lost partial or all of their teeth. The mean number of lost
      teeth was 7.38. The number of teeth present had a negative correlation to ages
      (P<0.01). The state of periodontal health also had a negative correlation to
      ages(P<0.01). 10.20% was the edentate and 98.98% of them were wearing complete
      dentures. Among the elderly with part of their teeth lost, 36.04% had prosthetic
      restoration. CONCLUSION: Teeth loss is common in elderly population. Dental
      caries and periodontal diseases are two main causes. To increase the treatment
      rates of dental disease, it is evident to improve the oral health awareness in
      elder persons.

PMID- 14966638
TI  - [Observation of blood supplies system to mandible in transparent specimen].
AB  - OBJECTIVE: To search for a direct observation method in blood supply system of
      mandible. METHODS: Six specimens of mandible were made transparent specimens
      after the vascular system was perfused with Chinese ink from the common carotid
      artery, and the blood supply system of mandible were observed and analyzed.
      RESULTS: The distribution of mandibular arteries was distinctly demonstrated in
      transparent specimens. The normal mandible receives its blood supply from the
      inferior alveolar artery and the periosteal vessel meshwork. CONCLUSION: The
      transparent specimen is an effective observation method in blood supply system of
      mandible.

PMID- 14966639
TI  - [Biological effects of tetracycline and doxycycline on cultured human periodontal
      ligament cells].
AB  - OBJECTIVE: To explore the biological effects of tetracycline and doxycycline on
      cultured human periodontal ligament cells(HPDLCs). METHODS: Increasing
      concentrations of two drugs(1,5,20,100,500,2500 microg/ml)were added to the
      medium of cultured HPDLCs separately. After being co-incubated for 2 days, cell
      morphology was observed under reverse microscope; meanwhile, cell proliferation
      activity was assayed using MTT, the total amount of protein was detected by
      Coumassie Bright Blue method and DNA synthesis was measured by 3H-TdR. RESULTS:
      Over a concentration range of 1 to 100 microg/ml, cell morphology was normal.
      Moreover, at a concentration range of 20 to 100 microg/ml, tetracycline
      significantly enhanced the proliferative activity and biosynthesis of HPDLCs
      (P<0.01) while doxycycline significantly promoted DNA synthesis only at the
      concentration of 20 microg/ml. However, higher concentration of the two drugs
      (2500 microg/ml) not only changed cell morphology under microscope, but also
      significantly inhibited cellular activity. CONCLUSION: The results suggested that
      proper doses of tetracycline could promote proliferation and biosynthesis of
      HPDLCs,while doxycycline had limited effects on biobehavior of HPDLCs.
      Nevertheless, higher concentrations of the two drugs both had cytotoxic effect.

PMID- 14966640
TI  - [Expression of ICAM-1 and VCAM-1 in human ameloblastoma and odontogenic
      keratocyst].
AB  - OBJECTIVE: To study the expression of ICAM-1 and VCAM-1 in human ameloblastoma
      (AB) and odontogenic keratocyst (OKC) and investigate the relation of ICAM-1 and
      VCAM-1 with the pathologic characteristic of AB and OKC. METHODS: The specimens
      of 38 cases of AB, 10 cases of OKC, 7 cases of normal oral mucosa (NOM) were
      examined by streptovidin-biotin method. Their expression was analyzed combining
      the pathologic characteristics. RESULTS: Comparing AB with OKC and NOM, there was
      a significant difference in ICAM-1 and VCAM-1 (P<0.05). The positive expression
      of ICAM-1 in AB was 65.2%, much higher than that in NOM(14.3%). There was no
      difference between the expression of ICAM-1 in OKC(60.0%) and in NOM. The
      positive vessels number stained by VCAM-1 in AB was significantly higher than
      that in OKC and NOM. The expression of ICAM-1 and VCAM-1 had no correlation to
      age, sex, histological types, lesion locations(P>0.05). CONCLUSION: ICAM-1 and
      VCAM-1 play an important role in genesis, development of AB and OKC and are
      related to cell differentiation and proliferation.

PMID- 14966641
TI  - [Transforming the sintered ostrich cancellous bone to multiphasic calcium
      phosphate ceramic].
AB  - OBJECTIVE: To transform the sintered ostrich cancellous bone(ostrich true bone
      ceramic, OTBC) to multiphasic calcium phosphate ceramic and study its components
      and characterization. METHODS: The OTBC blocks were soaked in different
      concentration of sodium pyrophosphate (Na(4)P(2)O(7).H(2)O,NP) solution and
      heated to 1100 degrees C to transform its constitution from HAP into multiphasic
      calcium phosphate ceramics. Then the surface configuration of the material was
      observed by SEM and the following properties of the material:porosity,bending
      strength,mineral composition and element ratio were analyzed. RESULTS: The
      prepared material was a kind of porous calcium phosphate ceramic composed of beta
      TCP, HAP and NaCaPO(4). With increase of the NP concentration,the content of HAP
      decreased while beta-TCP and NaCaPO(4) increased. The average bending strength of
      the material was (1.95+/-0.46)Mpa,the Ca/P element ratio was 1.511 and the
      average porosity was(60.71+/-6.9)%. The pore size was uneven. CONCLUSION: The
      OTBC could be transformed into beta-TCP /HAP /NaCaPO(4) multiphasic calcium
      phosphate ceramic by heating with NP. With characteristic porous structure, the
      prepared OTBC could become a new type of bone graft.

PMID- 14966642
TI  - [A study on the levels of soluble intercellular adhesion molecule-1 in the
      gingival crevicular fluid of the malocclusion patients with fixed appliances].
AB  - OBJECTIVE: To investigate the levels of soluble intercellular adhesion molecule
      1(sICAM-1) shed into the gingival crevicular fluid (GCF) of 31 malocclusion
      cases, who received fixed appliances orthodontic treatment in period of pre
      treatment, 1,4,8 weeks of treatment. To determine if the fixed appliance will
      affect the periodontal health. METHODS: The soluble intercellular adhesion
      molecule-1 in gingival crevicular fluid carefully collected with standardized
      filter strips from 31 patients with fixed appliance were measured,using an ELISA
      technique. The relation between the level of GCF and sICAM-1 during treatment was
      analyzed. RESULTS: After one week of treatment, the levels of sICAM-1 in GCF
      increased significantly. CONCLUSION: Using fixed appliances will affect the
      periodontal health. The levels of soluble intercellular adhesion molecule-1 in
      GCF can be used as an efficient method for monitoring periodontal health during
      orthodontic treatment.

PMID- 14966643
TI  - [Study on the location of mandibular foramen and the measurement of sigmoid notch
      and ramus].
AB  - OBJECTIVE: To compare the location of mandibular foramen in male and female,ang
      to observe and measure the sigmoid notch and ramus. METHODS: The mandibles of 74
      male and 79 female adults from Shanghai were used for the study. The vertical
      dimension from the center of mandibular foramen to the lowest point of sigmoid
      notch and the horizontal distance to the posterior margin of ramus were
      measured,including the depth and the width of sigmoid notch and the height of
      ramus. The figures were compared between male and female adults. RESULTS: The
      average distance of mandibular foramen to ramus and sigmoid notch in men and
      women were 16.75mm,24.50mm and 16.08mm,23.13mm. The average width and depth of
      sigmoid notch in men and women were 34.20mm,15.33mm and 32.69mm,14.49mm. The
      average height of ramus in men and women were 61.62mm,57.19mm. CONCLUSION: The
      difference of vertical dimension from the center of mandibular foramen to the
      lowest point of sigmoid notch and the horizontal distance to the posterior margin
      of ramus between male and female adults was not significant, and that of the
      depth and the width of sigmoid notch and the height of ramus between male and
      female adults was not significant,either.

PMID- 14966644
TI  - [Radioimmunological analysis of beta 2-MG in the fluid of gingival sulcus in
      patients with chronic periodontitis].

PMID- 14966645
TI  - [The distribution of Candida spp. in the oral cavities of normal children].
AB  - OBJECTIVE: To study the distribution of Candida spp. mainly Candida albicans in
      the oral cavities of health children. METHODS: Four groups children of different
      ages, A1: newborn babies, A2: 3.2 years old (average) children,A3, 7.2 years
      old,A4:12.7 years old and B control group 20.4 years old,mucosal swab sampling
      with centrification,CHROMagar Candida identified culture medium for culture and
      identification, and different methods for isolating Candida albicans for A3
      group. RESULTS: The isolation rates of Candida spp were A1 7.5%,A2 70%,A3
      56.36%,A4 49.12%,B 27.5%,the proportion of Candida albicans also diversely,and
      the method of PCR was more sensitive than the one of culture. CONCLUSION: Candida
      spp can be isolated from the normal oral cavities in different aged children,
      most of them were Candida albicans,both the isolation rates of Candida spp and
      the proportion of Candida albicans were different.

PMID- 14966646
TI  - [Public awareness and evaluation of dental implantation in Europe and USA].

PMID- 14966647
TI  - [Observation of and clinical outcomes of oral rehabilitation after orthodontics
      in 42 patients with loss of teeth].

PMID- 14966648
TI  - [Clinical observation of microfilled sealant for first molars in children].

PMID- 14966649
TI  - [The clinical evaluation of treatment of 127 cases molar acute endodontitis].

PMID- 14966650
TI  - [Treatment of mandibular neoplasms with surgery and adjunctive microwave:a
      preliminary report].

PMID- 14966651
TI  - [Treatment for 87 cases of peripheral facial paralysis with the integration of
      TCM and Western medicine and the use of herbs and acupuncture & moxibustion].

PMID- 14966652
TI  - [Effect of pinyangmycin and dexamethasonum injection of 56 cases on treatment of
      venous malformation in maxillofacial regions].

PMID- 14966653
TI  - [Clinical analysis on 274 cases of longitudinal fracture of posterior teeth].

PMID- 14966654
TI  - [Treatment of maxillary deficiency with the combination of rapid maxillary
      expansion and maxillary protraction].

PMID- 14966655
TI  - [The clinical effect of ART and psychological guidance in treatment of carious
      deciduous teeth in preschool children].

PMID- 14966656
TI  - [Clinical analysis of 31 warthin tumours of the parotid gland].

PMID- 14966657
TI  - [Evaluation of the clinical results of modified tunnel filling methods].

PMID- 14966658
TI  - [Surgical management of carotid body tumor: report of 7 cases].

PMID- 14966659
TI  - The novel mutation K87E in ribosomal protein S12 enhances protein synthesis
      activity during the late growth phase in Escherichia coli.
AB  - Resistance to streptomycin in bacterial cells often results from a mutation in
      the rpsL gene that encodes the ribosomal protein S12. We found that a particular
      rpsL mutation (K87E), newly identified in Escherichia coli, causes aberrant
      protein synthesis activity late in the growth phase. While protein synthesis
      decreased with age in cells in the wild-type strain, it was sustained at a high
      level in the mutant, as determined using living cells. This was confirmed using
      an in vitro protein synthesis system with poly(U) and natural mRNAs (GFP mRNA and
      CAT mRNA). Other classical rpsL mutations (K42N and K42T) tested did not show
      such an effect, indicating that this novel characteristic is typical of ribosomes
      bearing the K87E mutant form of S12, although the K87E mutation conferred the
      streptomycin resistance and error-restrictive phenotypes also seen with the K42N
      and K42T mutations. The K87E (but not K42N or K42T) mutant ribosomes exhibited
      increased stability of the 70S complex in the presence of low concentrations of
      magnesium. We propose that the aberrant activation of protein synthesis at the
      late growth phase is caused by the increased stability of the ribosome.

PMID- 14966660
TI  - Clinical features of Chiari I malformations.
AB  - BACKGROUND: With the advent of MRI, the diagnosis of Chiari I malformation is
      being made in younger patients, often with minimal or no neurologic symptoms.
      CLINICAL FEATURES: The symptoms and signs of a Chiari I malformation may be
      related to the compression of neural and/or dural structures at the cranio
      cervical junction or may be related to the associated syringomyelia. Scoliosis is
      a particularly important and common finding in those children with syringomyelia.

PMID- 14966661
TI  - International survey on the management of Chiari I malformation and
      syringomyelia.
AB  - INTRODUCTION: The availability of magnetic resonance imaging (MRI) has resulted
      in an increasing number of asymptomatic, minimally symptomatic, and doubtfully
      symptomatic patients being diagnosed with a Chiari I malformation with or without
      syringomyelia. In an attempt to clarify how neurosurgeons manage these clinical
      problems, an international survey on the Chiari I malformation and related
      syringomyelia was undertaken. METHOD: A questionnaire on the expected natural
      course of the disease and on aspects of the surgical technique for a number of
      hypothetical cases relating to Chiari I malformation with and without
      syringomyelia was used to survey Pediatric Neurosurgeons worldwide. RESULTS: Of
      246 questionnaires distributed, 76 (30.8%) were completed and returned. There was
      a consensus that no operation should be carried out in asymptomatic patients with
      a Chiari I malformation, unless there is associated syringomyelia. There was a
      consensus that decompression of the Chiari malformation should be performed in
      patients with scoliosis when syringomyelia is present, and the majority
      decompressed the Chiari malformation in scoliotic patients even in the absence of
      syringomyelia. Suboccipital decompression was the standard surgical procedure for
      Chiari I malformations. The majority of respondents favored routine dural opening
      at surgery and closure with a pericranial or synthetic patch graft. In the case
      of a persistent or progressive syrinx after suboccipital decompression, the
      majority recommended shunting of the syrinx to the subarachnoid space or to the
      pleural cavity. CONCLUSION: There continues to be much variation in the
      management of the Chiari I malformation.

PMID- 14966662
TI  - Secretory and extracellular production of recombinant proteins using Escherichia
      coli.
AB  - Escherichia coli is one of the most widely used hosts for the production of
      recombinant proteins. However, there are often problems in recovering substantial
      yields of correctly folded proteins. One approach to solve these problems is to
      have recombinant proteins secreted into the periplasmic space or culture medium.
      The secretory production of recombinant proteins has several advantages, such as
      simplicity of purification, avoidance of protease attack and N-terminal Met
      extension, and a better chance of correct protein folding. In addition to the
      well-established Sec system, the twin-arginine translocation (TAT) system has
      recently been employed for the efficient secretion of folded proteins. Various
      strategies for the extracellular production of recombinant proteins have also
      been developed. For the secretory production of complex proteins, periplasmic
      chaperones and protease can be manipulated to improve the yields of secreted
      proteins. This review discusses recent advances in secretory and extracellular
      production of recombinant proteins using E. coli.

PMID- 14966663
TI  - Bacterial lipases: an overview of production, purification and biochemical
      properties.
AB  - Lipases, triacylglycerol hydrolases, are an important group of biotechnologically
      relevant enzymes and they find immense applications in food, dairy, detergent and
      pharmaceutical industries. Lipases are by and large produced from microbes and
      specifically bacterial lipases play a vital role in commercial ventures. Some
      important lipase-producing bacterial genera include Bacillus, Pseudomonas and
      Burkholderia. Lipases are generally produced on lipidic carbon, such as oils,
      fatty acids, glycerol or tweens in the presence of an organic nitrogen source.
      Bacterial lipases are mostly extracellular and are produced by submerged
      fermentation. The enzyme is most commonly purified by hydrophobic interaction
      chromatography, in addition to some modern approaches such as reverse micellar
      and aqueous two-phase systems. Most lipases can act in a wide range of pH and
      temperature, though alkaline bacterial lipases are more common. Lipases are
      serine hydrolases and have high stability in organic solvents. Besides these,
      some lipases exhibit chemo-, regio- and enantioselectivity. The latest trend in
      lipase research is the development of novel and improved lipases through
      molecular approaches such as directed evolution and exploring natural communities
      by the metagenomic approach.

PMID- 14966664
TI  - Modern aspects of mushroom culture technology.
AB  - The production and culture of new species of mushrooms is increasing. The
      breeding of new strains has significantly improved, allowing the use of strains
      with high yield and resistance to diseases, increasing productivity and
      diminishing the use of chemicals for pest control. The improvement and
      development of modern technologies, such as computerized control, automated
      mushroom harvesting, preparation of compost, production of mushrooms in a non
      composted substrate, and new methods of substrate sterilization and spawn
      preparation, will increase the productivity of mushroom culture. All these
      aspects are crucial for the production of mushrooms with better flavor,
      appearance, texture, nutritional qualities, and medicinal properties at low cost.
      Mushroom culture is a biotechnological process that recycles ligninocellulosic
      wastes, since mushrooms are food for human consumption and the spent substrate
      can be used in different ways.

PMID- 14966665
TI  - Influence of media and temperature on bacteriocin production by Bacillus cereus
      8A during batch cultivation.
AB  - Cerein 8A is a bacteriocin produced by the soil bacterium Bacillus cereus 8A,
      isolated from native woodlands of Brazil. The influence of temperature and media
      on the growth of B. cereus 8A and the production of this bacteriocin was studied
      during batch cultivation. Maximum activity was detected by cultivation in
      brain/heart infusion broth, reaching 3200 activity units ml(-1). Bacteriocin was
      also produced in peptone, MRS, Mueller-Hinton and nutrient broth, while no
      activity was observed during cultivation in thioglycollate or tryptic soy broth.
      Temperature had a strong influence on bacteriocin production, which was higher at
      30 degrees C than at 25 degrees C. An important decrease in bacteriocin activity
      was observed at 37 degrees C. The relationship between growth and specific
      production rates, as a function of the temperature, showed different kinetics of
      production and there were several peaks in the specific production rates during
      growth. Bacteriocin was produced at the stationary phase, indicating it is
      synthesized as a secondary metabolite.

PMID- 14966666
TI  - Femoral and whole-body bone mineral density in middle-aged and older Norwegian
      men and women: suitability of the reference values.
AB  - The aim of this study was to compare bone mineral density (BMD) in a population
      based sample of middle-aged and older Norwegians, with reference values provided
      by the manufacturer of the densitometer (Lunar) in order to evaluate whether
      these reference values are suitable for Norwegians. Additional aims were to
      estimate the prevalence of osteoporosis. Bone mineral density of the hip and
      total body was measured by dual-energy X-ray absorptiometry in 2303 men and 3105
      women 47-50 and 71-75 years old, respectively, in western Norway, as part of the
      Hordaland Health Study (HUSK). Of these, 3403 white individuals were free of
      medications or diseases known to influence bone metabolism (reference group).
      Compared with the Lunar reference population, men and older women had a slightly
      but significantly lower BMD of trochanter and total femur and middle aged women
      had significantly higher total body BMD. Except for the higher mean BMD of total
      body among middle-aged women and the uniformly lower BMD values of Ward's
      triangle, the deviations from the reference values of the manufacturer were less
      than 4%. Approximately 2.6% of middle-aged men vs 0.9% of middle-aged women were
      classified as osteoporotic on the basis of BMD of femoral neck. While the BMD
      values for femoral neck in this healthy Norwegian population are similar to the
      reference population of Lunar, the values of trochanter and total femur are lower
      in all groups except middle-aged women; however, the discrepancies are not of
      sufficient magnitude to warrant rejection of this commonly used database among
      Norwegians. Use of the young adult means from the Lunar reference database
      classified a higher proportion of middle-aged men than women as osteoporotic and
      osteopenic.

PMID- 14966669
TI  - The unreamed intramedullary tibial nail in tibial shaft fractures of soccer
      players: a prospective study.
AB  - Lower leg fractures are common and complex injuries in soccer players. Twenty
      five mainly recreational soccer players who sustained a tibial shaft fracture
      were treated with the AO-UTN (Unreamed Tibial Nail). This prospective series
      included 25 males with a mean age of 28.1 years. These patients were
      prospectively followed for a mean period of 4.7 years. Clinical and radiographic
      data was collected. In addition, 20 patients completed an outcomes based
      questionnaire. In all but one case, the mechanism of injury was a contact with an
      opposing player. Shin guards provided little prevention against these fractures.
      The majority of these tibial shaft fractures were consistent with a short oblique
      or transverse fracture pattern. All fractures were stabilized with the UTN on the
      day of injury. Four patients had concurrent compartment syndromes and underwent a
      fasciotomy. Average time until bony consolidation was 11.3 weeks. No patients
      returned to competitive soccer activities earlier than five months after the
      initial injury (average 9.5). Only 11 out of 20 soccer players returned to the
      same level of sporting activity. Six patients never returned to playing soccer
      again after this injury, even without complications. The fracture of the tibial
      shaft in soccer players is a severe injury that can be treated safely with the
      UTN without major complications, but nevertheless only 50% of a mainly
      recreational playing population return to the same competitive level as before
      the injury.

PMID- 14966670
TI  - What did she "really" want?

PMID- 14966671
TI  - Severe agitation among ventilated medical intensive care unit patients:
      frequency, characteristics and outcomes.
AB  - OBJECTIVE: To determine the frequency, characteristics and outcomes of severe
      agitation among ventilated medical intensive care unit (MICU) patients. DESIGN:
      Prospective cohort study. SETTING: Eighteen-bed MICU in 964-bed tertiary care
      center. PATIENTS: All ventilated patients, aged 18 years or older and admitted
      for more than 24 h between January 1, 2001 and May 8, 2001. INTERVENTIONS: None.
      MEASUREMENTS: Data were collected daily by concurrent chart abstractions.
      Variables included sociodemographic, clinical, laboratory, pharmacologic and non
      pharmacologic interventions, ventilator settings and adverse events. Severe
      agitation, the main outcome variable, was defined as two or more Motor Activity
      Assessment Scale (MAAS) scores above 4 in a 24-h period and sedative and/or
      narcotic doses above the established sedation and analgesia protocol or a
      combination of two or more sedatives. RESULTS: Twenty-three (16.1%) of 143
      enrolled patients exhibited severe agitation. Agitated patients were younger
      (hazard ratio [HR] 1.32), more likely to be admitted from an outside hospital ICU
      (HR 2.48), had lower pH (HR 1.55) and PaO(2)/FIO(2) less than 200 mmHg (HR 2.59).
      Agitated patients had longer MICU stays (median 12 versus 5 days, p<0.0001) and
      more ventilator days (median 14 versus 6, p<0.0001). Agitated patients were more
      likely to self-extubate (26% versus 6%, p=0.002). Benzodiazepines, narcotics and
      neuromuscular blocking agents were administered more frequently and at higher
      doses, but haloperidol was not. CONCLUSION: Severe agitation occurs commonly in
      critically ill patients and is associated with adverse events including longer
      ICU stays, duration of mechanical ventilation and self-extubation.

PMID- 14966672
TI  - Hyperglycaemia potentiates the teratogenicity of retinoic acid in diabetic
      pregnancy in mice.
AB  - AIMS/HYPOTHESIS: We recently showed in mice that maternal diabetes increases
      embryonic susceptibility to caudal regression induced by vitamin A metabolite
      retinoic acid. Here we tested whether in the maternal diabetic milieu
      hyperglycaemia is the critical factor responsible for mediating this increased
      susceptibility. METHODS: Non-diabetic pregnant mice were made hyperglycaemic by
      subcutaneous injections of glucose at regular intervals. Conversely, diabetic
      pregnant mice were treated with phlorizin to induce renal glucosuria and thus
      reduce blood glucose concentrations. Pregnant mice were treated with retinoic
      acid and the extent of caudal regression in mouse embryos, measured in terms of
      the ratio of tail length to crown-rump length was assessed. Embryos were also
      examined for Wnt-3a expression and cell death. RESULTS: Embryos of mice treated
      with glucose had a greater extent of caudal regression induced by retinoic acid
      than saline-treated controls, with enhanced down-regulation of Wnt-3a expression
      and exacerbated cell death specifically at the caudal end of the embryo. Embryos
      of diabetic mice treated with phlorizin had a similar extent of caudal regression
      to embryos of non-diabetic mice after treatment with retinoic acid.
      CONCLUSIONS/INTERPRETATION: Hyperglycaemia increases embryonic susceptibility to
      caudal regression induced by retinoic acid, with the underlying cellular and
      molecular changes closely mimicking those that occur in maternal diabetes.
      Reduction of blood glucose concentrations in diabetic mice completely abolishes
      this increased susceptibility to retinoic acid. These results suggest that in
      maternal diabetes hyperglycaemia is the critical factor responsible for
      potentiating the teratogenic effect of retinoic acid.

PMID- 14966673
TI  - Incorporating genotyping uncertainty in haplotype inference for single-nucleotide
      polymorphisms.
AB  - The accuracy of the vast amount of genotypic information generated by high
      throughput genotyping technologies is crucial in haplotype analyses and linkage
      disequilibrium mapping for complex diseases. To date, most automated programs
      lack quality measures for the allele calls; therefore, human interventions, which
      are both labor intensive and error prone, have to be performed. Here, we propose
      a novel genotype clustering algorithm, GeneScore, based on a bivariate t-mixture
      model, which assigns a set of probabilities for each data point belonging to the
      candidate genotype clusters. Furthermore, we describe an expectation-maximization
      (EM) algorithm for haplotype phasing, GenoSpectrum (GS)-EM, which can use
      probabilistic multilocus genotype matrices (called "GenoSpectrum") as inputs.
      Combining these two model-based algorithms, we can perform haplotype inference
      directly on raw readouts from a genotyping machine, such as the TaqMan assay. By
      using both simulated and real data sets, we demonstrate the advantages of our
      probabilistic approach over the current genotype scoring methods, in terms of
      both the accuracy of haplotype inference and the statistical power of haplotype
      based association analyses.

PMID- 14966674
TI  - Molecular cytogenetic assignment of genes to bovine chromosome 5.
AB  - Seven genes were assigned by molecular cytogenetic methods to bovine chromosome
      5. To accomplish this, specific primers were either publicly available or were
      designed from highly conserved regions of the publicly available mammalian gene
      sequences. The identity of the amplified segments was verified by sequencing and
      alignment with the published sequences. The optimized primers that amplified the
      desired bovine genes were used for screening a bovine bacterial artificial
      chromosome library. The positive clones were localized to a specific band of
      bovine chromosome 5 by fluorescence in situ hybridization. The genes HOXC4, SP1
      and IGFBP6 were localized to band q21, COL2A1 was localized to bands q21-q23,
      IGF1 was localized to band q26, MB to band q31 and the gene CYP2D6 was localized
      to band q35. The cytogenetic assignment of SP1, IGFBP6, COL2A1, IGF1, MB and
      CYP2D6 is first reported here and the assignment of HOXC4 refines the previous
      assignment of this gene. The identification and localization of these genes
      further support the development of the human to bovine comparative map through
      characterizing the homologous segments conserved in the evolution of these
      species. This information will be useful for the future localization of genes
      that affect economically important traits in bovines.

PMID- 14966675
TI  - Relationships of weight and height with age in hybrid Holstein-Friesian/Guzera
      females.
AB  - Serial data on live weights, height at withers and the weight/height ratio of 263
      cows (3 to 9 years old) and 196 heifers (2 to 5 years old) were studied. The
      animals were of six red and white Holstein-Friesian (HF)/Guzera crosses (1/4,
      1/2, 5/8, 3/4, 7/8 and > or = 31/32 HF-expected gene fraction). Separate analyses
      were performed for cows and heifers using the Proc Mixed of the SAS package.
      Models included the fixed effects of farm, season, reproductive and lactation
      status, two-factor interactions, quadratic regressions on age and age x crossbred
      group interaction, as continuous co-variables and regressions on the HF gene
      fraction and on breed heterozygosity, plus the animal random effect. Only heifer
      growth in height and weight/height was linear with age. In all three traits in
      both categories the individual additive-dominance model explained the variation
      between crossbred groups. The breed additive difference was not significant (P >
      0.05) for cow and heifer live weight and for heifer weight/age ratio. Heterosis
      was significant for all traits except height of cows. Linear and quadratic
      regression coefficients for cows, were, respectively, for live weight, 35.20 +/-
      5.23 kg/year and -1.54 +/- 0.43 kg/year2, for withers height, 2.49 +/- 0.29
      cm/year and -0.15 +/- 0.02 cm/year2 and for weight/height, 0.22 +/- 0.04
      kg/cm/year and -0.01 +/- 0.003 kg/cm/year2. Corresponding values for heifers
      were, for live weight, 153.46 +/- 37.06 kg/year and -15.69 +/- 4.91 kg/year2,
      while only linear coefficients applied to withers height (1.63 +/- 0.43 cm/year)
      and weight/height (0.16 +/- 0.03 kg/cm/year).

PMID- 14966676
TI  - Non-Darwinian and Darwinian prokaryotic and eukaryotic evolution--an enigma in
      cell biology conservation.
AB  - Our theory is embarrassingly simple. What made today's prokaryotes and modern
      cyanobacteria so robust is the fact that in their origin, back in the Archean (3
      billion years ago), selection did not play a central role in evolution, it had
      only a transitory role. Asexual reproduction, mutation, drift and sampling
      variance in local demes were more important especially when they were accompanied
      by population catastrophes, where millions perished. Metazoans are generally
      macroscopic, sexually reproducing, ecologically specialized organisms whose
      history is full of extinctions and radiations leading to morphological change. On
      the other hand, prokaryotes, thanks to their origin, avoid extinction because as
      a group they have slowly evolved as generalists. Specialization appears to be
      less important than ecological versatility and metabolic unspecialization. Modern
      cyanobacteria keep on using that strategy.

PMID- 14966677
TI  - Genetic, biochemical, and characterization of neurological mutant 3, a new mouse
      model for Parkinson's disease.
AB  - We have identified a new mutant mouse that we have named new mouse neurological
      mutant 3 (NM3); it may be a useful model to understand the underlying molecular
      and genetic basis of Parkinson's disease (PD). A mouse carrying the NM3 mutation
      arose spontaneously in an RIIIS/J breeding colony and was identified as having a
      movement disorder. Upon neurological examination of these mice, their movement
      was found to be slow and abnormal, with characteristic choreaform and
      bradykinetic-type movements, typical of PD. The importance of the gene mutation
      in NM3 in the molecular pathway involved in this pathology is underscored by the
      fact that these mice do not survive past weaning age if they are homozygous for
      the genetic mutation. We localized the gene mutation by positional cloning and
      genetic mapping to mouse chromosome 2 in an area that corresponds to human
      chromosome 2q24-31, which does not contain any known genes associated with PD.
      However, there was a significant decrease of 15-20% in the levels of dopamine,
      and its principal metabolite, 3,4-dihydroxyphenylacetic acid, in the midbrain of
      affected mice. Low concentrations of these substances are associated with PD in
      human patients, making these mutant mice candidates for studies of this disease.

PMID- 14966678
TI  - Effects of crude extracts of Agaricus blazei on DNA damage and on rat liver
      carcinogenesis induced by diethylnitrosamine.
AB  - The effects of crude extracts of the mushroom Agaricus blazei Murrill
      (Agaricaceae) on both DNA damage and placental form glutathione S-transferase
      (GST-P)-positive liver foci induced by diethylnitrosamine (DEN) were
      investigated. Six groups of adult male Wistar rats were used. For two weeks,
      animals of groups 3 to 6 were treated with three aqueous solutions of A. blazei
      (mean dry weight of solids being 1.2, 5.6, 11.5 and 11.5 mg/ml, respectively).
      After this period, groups 2 to 5 were given a single ip injection 200 mg/kg DEN
      and groups 1 and 6 were treated with 0.9% NaCl. All animals were subjected to 70%
      partial hepatectomy at week five and sacrificed 4, 24 and 48 h or 8 weeks after
      DEN or 0.9% NaCl treatments (10th week after the beginning of the experiment).
      The alkaline comet assay and GST-P-positive liver foci development were used to
      evaluate the influence of the mushroom extracts on liver cell DNA damage and on
      the initiation of liver carcinogenesis, respectively. Previous treatment with the
      highest concentration of A. blazei (11.5 mg/ml) significantly reduced DNA damage,
      indicating a protective effect against DEN-induced liver
      cytotoxicity/genotoxicity. However, the same dose of mushroom extract
      significantly increased the number of GST-P-positive liver foci.

PMID- 14966679
TI  - Is the number of antennal plate organs (sensilla placodea) greater in hygienic
      than in non-hygienic Africanized honey bees?
AB  - Hygienic behavior is a desirable trait in honey bees (Apis mellifera L.), as
      hygienic bees quickly remove diseased brood, interrupting the infectious cycle.
      Hygienic lines of honey bees appear to be more sensitive to the odors of dead and
      diseased honey bee brood, and Africanized honey bees are generally more hygienic
      than are European honey bees. We compared the number of sensilla placodea,
      antennal sensory structures involved in the perception of odor, in 10 bees from
      each of six hygienic and four non-hygienic colonies of Africanized honey bees.
      The sensilla placodea of three of the terminal segments (flagellomeres) of the
      right antenna of each bee were counted with a scanning electron microscope. There
      were no significant differences in the mean numbers of sensilla placodea between
      the hygienic and non-hygienic bees, though the variance was higher in the
      hygienic group. Flagellomere 4 had significantly more sensilla placodea than
      flagellomeres 6 and 8. However, there was no significant difference between the
      other two flagellomeres. As hygienic bees are capable of identifying dead,
      injured, or infested brood inside a capped brood cell, sensilla placodea probably
      have an important role in enabling worker bees to sense sick brood. However, we
      did not find greater numbers of this sensory structure in the antennae of
      hygienic, compared to non-hygienic Africanized honey bees.

PMID- 14966680
TI  - Yield and post-harvest quality of tomato hybrids heterozygous at the loci
      alcobaca, old gold-crimson or high pigment.
AB  - The effects of the fruit ripening mutant gene alcobaca (alc) and color
      development mutants, old gold-crimson (ogc) and high pigment (hp), on yield and
      post-harvest quality of tomato fruits were investigated. Five tomato hybrids were
      obtained by crossing near isogenic lines with Flora-Dade background [Flora-Dade
      (alc+/alc+ ogc+/ogc+ hp+/hp+), TOM-559 (alc/alc ogc+/ogc+ hp+/hp+), TOM-591
      (alc/alc ogc/ogc hp+/hp+), TOM-593 (alc/alc ogc+/ogc+ hp/hp), and TOM-589
      (alc/alc ogc/ogc hp/hp)] with the pollen parent line Mospomorist (alc+/alc+
      ogc+/ogc+ hp+/hp+). Hybrid fruit was harvested at the breaker stage and stored on
      shelves at 15oC and 60% relative humidity for 16 days, and then evaluated for
      firmness, development of red color, and carotenoid contents. The different
      genotypic combinations at the loci alc, ogc and hp had no effect on fruit yield.
      The alc+/alc hybrid genotype significantly increased fruit firmness and
      significantly delayed the development of red color in maturing fruit.
      Simultaneous usage of ogc+/ogc and hp+/hp promoted an increase in the red color
      and lycopene content of alc+/alc hybrids, but did not have any additional effect
      on fruit firmness.

PMID- 14966681
TI  - Evaluation of the mutagenic activity of hydroxyurea on the G1-S-G2 phases of the
      cell cycle: an in vitro study.
AB  - Hydroxyurea is considered an antineoplastic drug, which also plays an important
      role in the treatment of sickle cell anemia patients. We evaluated and compared
      the clastogenic and cytotoxic effects of hydroxyurea, using chromosomal
      aberrations and mitotic index, respectively, as endpoints. In vitro short-term
      cultures of lymphocytes were exposed to several concentrations of this drug, at
      various cell cycle phases. There was a significant increase in the cytotoxicity
      of hydroxyurea at G1 and G1/S as well in the G2 phase of the cell cycle.
      Hydroxyurea did not significantly increase chromosome aberrations. There was an S
      dependent cytotoxic effect of hydroxyurea, which is expected based on the known
      activity of hydroxyurea as an inhibitor of ribonucleotide reductase.

PMID- 14966682
TI  - Evaluation of a method for high yield purification of largely intact
      mitochondrial DNA from human placentae.
AB  - We developed, and quantitatively and qualitatively evaluated an easily
      reproducible method for high yield purification of mitochondrial DNA (mtDNA) from
      human placentae by mechanical tissue disruption, differential centrifugation of
      mitochondria, enzymatic digestion, phenol extraction and ethanol precipitation.
      Average mtDNA yields were 2.5 microg/g tissue (without an RNAse treatment step)
      and 1.5 microg/g tissue (with an RNAse treatment step). This mtDNA migrated as a
      16.5-kb isolated band in agarose gels; it yielded fragments of expected sizes
      after digestion with restriction enzymes; it successfully served as a template in
      long PCR for amplification of mtDNA sequences, and hybridized to an mtDNA probe
      in a predictable fashion. MtDNA yields of this method were 10-fold higher than
      those of previously reported ones for mtDNA purification from freshly obtained
      human cells and tissues, with the advantage that more placental tissue can be
      obtained for mtDNA purification than other types of tissue, at lower cost, and
      with minimal or no ethical issues.

PMID- 14966683
TI  - Anti-P53 antibodies in Brazilian brain tumor patients.
AB  - Gliomas of astrocytic origin are the most common primary brain tumors, accounting
      for over 40 to 50% of all central nervous system tumors. The TP53 tumor
      suppressor gene is the most frequently mutated gene found in human malignancies.
      A mutation of this gene can lead to an increased half-life of the resulting
      protein and loss of biological function. High levels of p53 have been detected in
      the serum of colon cancer patients, although p53 protein has not been detected in
      the serum of brain tumor patients. Besides circulating p53, several studies have
      detected antibodies against p53 in patients with lung and breast cancer, as well
      as those with other types of cancer. We studied p53 protein and anti-p53
      antibodies in the plasma of Brazilian brain tumor patients. Plasma samples were
      drawn from 24 untreated brain tumor patients and from 15 healthy donors without
      clinical signs of cancer. Western blotting techniques were used to detect p53
      protein and anti-p53 antibodies. We found anti-p53 antibodies in 5/24 brain tumor
      patients. Age appears to affect the immune response, as four of six tumor
      patients under 16 years old had detectable anti-p53 antibodies, while these were
      found in only 1 of 18 adults (over 16 years old). We found no p53 protein in any
      of the serum samples from the brain tumors. Possibly the presence of this protein
      is affected by tumor type or by the organs that are sampled.

PMID- 14966684
TI  - Comparative study of the cuticular hydrocarbon composition of Melipona bicolor
      Lepeletier, 1836 (Hymenoptera, Meliponini) workers and queens.
AB  - In social insects, cuticular hydrocarbons are involved in species, kin, caste and
      nestmate recognition. Gas chromatography and mass spectrometry were used to
      compare the cuticular hydrocarbon composition of workers, males and queens of
      Melipona bicolor. The cuticular hydrocarbon composition of this species was found
      to consist mainly of C23, C25:1, C25, C27:1, C27, C29:1 and C29, which are
      already present in imagoes that have not yet abandoned the brood cell. This
      composition varied quantitatively and qualitatively between and within the castes
      and sexes. The newly emerged workers and young queens (virgins) had similar
      cuticular hydrocarbon profiles, which were different from those of the males.
      When the females start executing their tasks in the colony, the cuticular
      hydrocarbon profile differences appear. The workers have less variety, while the
      queens conserve or increase the number of cuticular hydrocarbon compounds. The
      queens have more abdominal tegumentary glands than the workers, which apparently
      are the source of the new cuticular compounds.

PMID- 14966685
TI  - Birth of normal kids after microinjection of pronuclear embryos in a transgenic
      goat (Capra hircus) production program in Brazil.
AB  - This pilot project was designed to determine if normal kids could be produced
      after microinjection in pronuclear embryos and subsequent transfer to recipients
      in a transgenic goat program in Brazil. Twelve donors of the Saanen breed and 17
      recipients of an undefined breed were used. The estrus of both donors and
      recipients was synchronized by a standard progestagen treatment and
      superovulation obtained by six pFSH injections. Donors in estrus were mated with
      fertile Saanen bucks. Zygotes were recovered surgically by flushing oviducts. The
      recovered zygotes with visible pronuclei were microinjected with 500 to 1000
      copies of the human G-CSF gene. Two or four embryos were surgically transferred
      into the oviducts of recipients. One recipient became pregnant and two kids were
      born. No transgenic goat was identified after PCR analysis. Even though
      transgenic goats were not obtained, this experiment establishes the basis of a
      synchronization and superovulation regimen for use in goats raised in Brazil, for
      the purpose of collecting and manipulating the pronuclear embryos. This project
      also showed that microinjected one-cell goat embryos can survive to produce live
      young following surgical transfer.

PMID- 14966686
TI  - Diallel analysis of production traits among domestic, exotic and mutant
      germplasms of Lycopersicon.
AB  - The effects of wild germplasm on tomato fruit shelf life have not yet been
      completely evaluated. Three different genotypes of Lycopersicon esculentum (a
      cultivated variety, a homozygote for nor and a homozygote for rin), LA1385 of L.
      esculentum var. cerasiforme, LA722 of L. pimpinellifolium, and 10 diallel hybrids
      were assayed. Mean values of fruit shelf life, weight, shape, and mean number of
      flowers per cluster were analyzed after Griffing (1956, Aust. J. Biology 9: 463
      493), method 2, model 1. Both general and specific combining abilities (GCA and
      SCA) were significant for the four traits. Negative unidirectional dominance was
      detected for fruit weight and shelf life, while bidirectional dominance was
      detected for fruit shape and mean number of flowers per cluster. SCA was greater
      than GCA for shelf life, so nonadditive effects predominantly accounted for this
      trait. In the heterozygous state, rin had smaller mean effects than nor. Wild
      accessions were able to prolong shelf life per se, and in crosses to the
      cultivated variety. The cross between the homozygote for nor and LA722 yielded
      the longest shelf life among hybrids.

PMID- 14966687
TI  - Cassava, Manihot esculenta Crantz genetic resources: VI. Anatomy of a diversity
      center.
AB  - Central Brasil is one of the four centers of diversity of Manihot species. Of 26
      wild Manihot species reported to occur in this region, 20 were collected from two
      limited areas, each less than 100 km in diameter. These two areas are Goias Velho
      and Corumba de Goias. Considering the Harlan concept of geographic patterns of
      variation of cultivated crops, it is assumed that the two areas are microcenters
      of cassava diversity. Topographic, soil and ethnological data of these species
      were collected and compared.

PMID- 14966688
TI  - The anticancer homeopathic composite "Canova Method" is not genotoxic for human
      lymphocytes in vitro.
AB  - The Canova Method (CM) is a homeopathic medicine indicated for the treatment of
      patients with cancer and for pathologies that involve a depressed immune system,
      such as AIDS. This product is composed of homeopathic dilutions of Aconitum
      napellus, Arsenicum album (arsenic trioxide), Bryonia alba, Lachesis muta venom
      and Thuya occidentalis. It stimulates the immune system by activating
      macrophages. Activated macrophages stimulate the lymphocytes so that they
      increase their cytotoxic action in response to tumoral growth or infection. Given
      that the CM stimulates and accelerates the activity of macrophages and
      lymphocytes, we evaluated genotoxic effects induced in human lymphocytes treated
      with this homeopathic medication in vitro. Structural and numerical chromosomal
      aberrations were scored for the assessment of induced genotoxic effects, while
      the variation in mitotic index was considered as a monitor for induced cellular
      toxicity. The lymphocytes were cultivated for 24, 48 or 72 h in the following
      final concentrations of the medicinal composite CM: 4, 8 and 12%. Treatments with
      the CM did not affect mitotic indexes, nor did they provoke chromosomal
      aberrations, when compared with untreated controls. There was no cytotoxicity or
      genotoxicity at the chromosomal level.

PMID- 14966689
TI  - Psorophora columbiae and Psorophora toltecum (Diptera: Culicidae) Colombian
      populations cannot be differentiated by isoenzymes.
AB  - Two populations of the mosquito Psorophora columbiae from the central Andean area
      of Colombia and one population of Ps. toltecum from the Atlantic coast of
      Colombia were analyzed for 11 isoenzyme markers. Psorophora columbiae and Ps.
      toltecum are two of the main vectors of Venezuelan equine encephalitis. We found
      no conspicuous genetic differences between the two species. The relatively high
      gene flow levels among these populations indicate that these are not two
      different species or that there has been recent divergence between these taxa. In
      addition, no global differential selection among the loci was detected, although
      the alpha-GDH locus showed significantly less genetic heterogeneity than the
      remaining loci, which could mean that homogenizing natural selection acts at this
      locus. No isolation by distance was detected among the populations, and a spatial
      population analysis showed opposite spatial trends among the 31 alleles analyzed.
      Multiregression analyses showed that both expected heterozygosity and the average
      number of alleles per locus were totally determined by three variables: altitude,
      temperature and size of the human population at the locality. Individually, the
      expected heterozygosity is more related to these three variables than to the
      average number of alleles.

PMID- 14966700
TI  - Working memory and mental practice outcomes after stroke.
AB  - OBJECTIVE: To examine the relationship between working memory and motor
      improvement obtained after a single training session combining mental and
      physical practice. DESIGN: Before-after trial. SETTING: Laboratory of a
      university-affiliated research rehabilitation center. PARTICIPANTS: A sample of
      12 patients with stroke and 14 age- and gender-matched healthy subjects.
      INTERVENTION: In a single session, patients were trained with combined mental and
      physical practice to increase the loading on the affected leg while standing up
      and sitting down. MAIN OUTCOME MEASURES: Motor improvement as measured by the
      percentage change in limb loading on the affected limb after training and 24
      hours later (follow-up), and the relationship between working memory and
      percentage motor improvement. RESULTS: The loading on the affected leg was
      improved after training (P< .01) and at follow-up (P< .05), and working memory
      scores at follow-up correlated significantly (P< .004 to P< .007) with the level
      of improvement. The visuospatial domain yielded the strongest correlation (r=
      .83), followed by the verbal (r= .62) and kinesthetic (r= .59) domains.
      CONCLUSIONS: These results suggest that the outcome (improved limb loading) of
      mental rehearsal with motor imagery depends on the ability to maintain and
      manipulate information in working memory.

PMID- 14966701
TI  - Impact of transfer delays to rehabilitation in patients with severe trauma.
AB  - OBJECTIVE: To measure the effect on rehabilitation outcomes of administrative
      delays in transferring patients from a level I trauma center to inpatient
      rehabilitation. DESIGN: Retrospective cohort study. SETTINGS: Level I trauma
      center and an inpatient rehabilitation center in Quebec, Canada. PARTICIPANTS: A
      total of 289 patients with severe trauma admitted to inpatient rehabilitation
      from a level I trauma center between 1994 and 1999. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Length of stay (LOS) in rehabilitation, motor
      and cognitive function at discharge from rehabilitation, interruptions in
      rehabilitation, and disposition at discharge. RESULTS: Shorter administrative
      delays were associated with shorter rehabilitation LOS (P<.01) improved cognitive
      function (P=.02) and had a negative but statistically nonsignificant association
      with motor function at discharge. No effect was observed for rehabilitation
      interruptions or dispositions at discharge. CONCLUSIONS: Transferring trauma
      patients more quickly to inpatient rehabilitation can affect rehabilitation
      outcomes positively. It can also lead to an economy of resource use in both acute
      and rehabilitation settings.

PMID- 14966702
TI  - Functional outcomes of intramuscular botulinum toxin type A in the upper limbs of
      children with cerebral palsy: a phase II trial.
AB  - OBJECTIVE: To describe the functional and family-centered assessment protocol and
      outcomes of a phase II trial evaluating upper-limb function after botulinum toxin
      injections in children with cerebral palsy (CP). DESIGN: Intervention study, case
      series, phase II trial, follow-up at 2 weeks and 3 and 6 months. SETTING:
      Specialist outpatient physical disabilities clinic within a public pediatric
      teaching hospital. PARTICIPANTS: Convenience sample of 16 children with CP (age
      range, 2-12y). INTERVENTIONS: Botulinum toxin type A (Botox) injections after
      electrical stimulation localization of appropriate muscle. MAIN OUTCOME MEASURES:
      The Canadian Occupational Performance Measure (COPM), Goal Attainment Scale
      (GAS), Melbourne Assessment of Unilateral Upper Limb Function, Child Health
      Questionnaire (CHQ), parent questionnaire, Modified Ashworth Scale (MAS), Tardieu
      scale, and active (AROM) and passive (PROM) range of motion. RESULTS: On the
      COPM, there was significant improvement at 3 months and 6 months. On the GAS, the
      T-scores were 42 and 47 at 3 and 6 months, respectively. On the Melbourne
      Assessment and CHQ, there was no significant change. The parent questionnaire
      indicated acceptability of injections and positive outcomes. On the MAS, there
      was a significant reduction in tone at 2 weeks, with a return to baseline by 6
      months. On the Tardieu scale, there was a significant increase in angle of first
      catch at 2 weeks, but only the elbow maintained a significant difference at 3 and
      6 months. No significant change was found for AROM or PROM. CONCLUSIONS:
      Sustained functional outcomes occurred after botulinum toxin injections despite
      increasing muscle tone after an initial reduction in tone. Randomized controlled
      trials are required.

PMID- 14966703
TI  - The cost and benefits of employment: a qualitative study of experiences of
      persons with multiple sclerosis.
AB  - OBJECTIVE: To attain a better understanding of the benefits and barriers faced by
      persons with multiple sclerosis (MS) in the workplace. DESIGN: Qualitative
      research methodology comprising a series of semistructured interviews. SETTING:
      Community-based setting. PARTICIPANTS: Fourteen women and 2 men with MS living in
      the community who were employed or recently employed at the time of interviews.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Accounts of personal
      experiences related to employment. RESULTS: Four themes emerged: the cost-benefit
      economy of working; fatigue and cognitive changes; stress in the workplace; and
      accommodations made to address barriers. Although participants valued work
      highly, they were also aware of the cost of being employed. The consequences of
      unemployment or changing jobs were considered negative and appeared stressful.
      For persons with MS, employment had both costs and significant benefits.
      Accommodations in the workplace and modifications of roles and responsibilities
      at home made it possible for individuals to continue working. CONCLUSIONS: Health
      care providers must consider the complexity and timing of decisions by people
      with MS to continue or leave employment before recommending either action.
      Identifying critical periods of intervention to stabilize this cost-benefit
      balance is a critical next step for understanding issues of employment and MS.

PMID- 14966704
TI  - Payer incentives and physical rehabilitation therapy for nonelderly institutional
      long-term care residents: evidence from Michigan and Ontario.
AB  - OBJECTIVE: To examine the effect of payment incentives on the provision of
      rehabilitation therapy to non elderly nursing home residents. DESIGN:
      Retrospective cross-sectional study. SETTING: Nursing homes in Michigan or
      complex continuing care facilities in Ontario, Canada, in 1998 or 1999.
      PARTICIPANTS: Non elderly nursing home residents (N=5189) admitted to nursing
      homes. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The effect of
      payment on access to physical therapy (PT) and occupational therapy (OT) and
      total weekly time for each therapy type. RESULTS: A Medicare policy change from
      cost-based to a patient-specific case-mix payment method was associated with
      greater likelihood of receiving OT but reduced weekly minutes of PT and OT
      provided to residents. Medicare cost-based and private insurance were associated
      with greater likelihood of receiving OT and PT and more therapy time for both
      types of therapy compared with private-pay residents. Global budget payment was
      associated with greater access to PT but fewer weekly minutes of OT and PT.
      CONCLUSIONS: Little information exists to describe the characteristics and
      treatment of non elderly nursing home residents. This study found that many of
      these residents received rehabilitation and that residents whose care was paid
      for by more generous payers, such as Medicare, received more therapy than those
      paid for by less generous payers.

PMID- 14966705
TI  - Evaluating diagnosis-based risk-adjustment methods in a population with spinal
      cord dysfunction.
AB  - OBJECTIVE: To examine performance of models in predicting health care utilization
      for individuals with spinal cord dysfunction. DESIGN: Regression models compared
      2 diagnosis-based risk-adjustment methods, the adjusted clinical groups (ACGs)
      and diagnostic cost groups (DCGs). To improve prediction, we added to our model:
      (1) spinal cord dysfunction-specific diagnostic information, (2) limitations in
      self-care function, and (3) both 1 and 2. SETTING: Models were replicated in 3
      populations. PARTICIPANTS: Samples from 3 populations: (1) 40% of veterans using
      Veterans Health Administration services in fiscal year 1997 (FY97) (N=1,046,803),
      (2) veteran sample with spinal cord dysfunction identified by codes from the
      International Statistical Classification of Diseases, 9th Revision, Clinical
      Modifications (N=7666), and (3) veteran sample identified in Veterans Affairs
      Spinal Cord Dysfunction Registry (N=5888). INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Inpatient, outpatient, and total days of care in FY97. RESULTS:
      The DCG models (R(2) range,.22-.38) performed better than ACG models (R(2)
      range,.04-.34) for all outcomes. Spinal cord dysfunction-specific diagnostic
      information improved prediction more in the ACG model than in the DCG model (R(2)
      range for ACG,.14-.34; R(2) range for DCG,.24-.38). Information on self-care
      function slightly improved performance (R(2) range increased from 0 to.04).
      CONCLUSIONS: The DCG risk-adjustment models predicted health care utilization
      better than ACG models. ACG model prediction was improved by adding information.

PMID- 14966706
TI  - Outcomes after rehabilitation for adults with balance dysfunction.
AB  - OBJECTIVES: To assess balance, dynamic gait, and dynamic visual acuity outcomes
      after a vestibular and balance rehabilitation program and to determine which
      variables were significantly associated with improved balance and ambulation.
      DESIGN: Retrospective case series. SETTING: Outpatient setting at a tertiary care
      facility. PARTICIPANTS: Twenty patients who were seen for vestibular and balance
      therapy between July 1999 and June 2000. INTERVENTIONS: A customized exercise
      program was developed for each patient according to the results of the assessment
      and included the following interventions, as indicated: gaze stabilization,
      balance and gait training, and habituation exercises. MAIN OUTCOME MEASURES: The
      Dynamic Gait Index (DGI), Berg Balance Scale (BBS), Dynamic Visual Acuity Test
      (DVAT), and computerized post urography (Sensory Organization Test [SOT]).
      RESULTS: The mean change scores for the DGI showed significant improvement for
      both patients with peripheral vestibular dysfunction and patients with central
      balance disorders. For the central balance disorders group, the BBS score also
      showed significant improvement. No difference was noted for pretherapy and
      posttherapy SOT scores between groups. The total group appeared to show an
      average improvement of more than 2 lines on the visual acuity chart on the
      clinical DVAT. Patients who were 66 years or older were 1.5 times more likely to
      score less than 20 on the DGI, and those whose pretherapy vertical dynamic visual
      acuity was 20/80 or worse were 1.3 times more likely to score less than 20 on the
      DGI. CONCLUSIONS: Patients showed functional improvements in balance, visual
      acuity, and gait stability after balance and vestibular physical therapy. Age and
      pretherapy vertical dynamic visual acuity score influenced dynamic gait outcome
      after a balance rehabilitation program.

PMID- 14966707
TI  - Community ambulation after stroke: how important and obtainable is it and what
      measures appear predictive?
AB  - OBJECTIVES: To assess how important community ambulation is to stroke survivors
      and to assess the relation between the level of community ambulation achieved and
      other aspects of mobility. DESIGN: A multicenter observational survey. SETTING:
      Community setting in New Zealand. PARTICIPANTS: One hundred fifteen stroke
      survivors living at home were referred from physical therapy (PT) services at 3
      regional hospitals at the time of discharge and were assessed within 1 week after
      returning home. Another 15 people with stroke who did not require further PT when
      discharged were assessed within 2 weeks after they returned home to provide
      insight into community ambulation status for those without mobility impairment,
      as recognized by health professionals. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Self-reported levels of community ambulation ascertained by
      questionnaire, gait velocity (m/min), Functional Ambulation Categories (FAC)
      score, and Rivermead Mobility Index (RMI) score. RESULTS: Mean gait velocity for
      the participants was 53.9 m/min (95% confidence interval [CI], 52.3-61.1); mean
      treadmill distance was 165.5 m (95% CI, 141.6-189.5); median RMI score was 14;
      and median FAC score was 6. Mobility scores for the 15 people who did not require
      PT were within the normal range. Based on self-reported levels of ambulation, 19
      (14.6%) participants were unable to leave the home unsupervised, 22 (16.9%) were
      walking as far as the letterbox, 10 (7.6%) were limited to walking within their
      immediate environment, and 79 (60.7%) could access shopping malls and/or places
      of interest. Participants with different levels of community ambulation showed a
      significant difference in gait velocity (P<.001). The ability to "get out and
      about" in the community was considered to be either essential or very important
      by 97 subjects (74.6%). CONCLUSIONS: Community ambulation is a meaningful outcome
      after stroke. However, despite good mobility outcomes on standardized measures
      for this cohort of home-dwelling stroke survivors, nearly one third were not
      getting out unsupervised in the community. Furthermore, gait velocity may be a
      measure that discriminates between different categories of community ambulation.
      These findings may have implications for PT practice for people with mobility
      problems after stroke.

PMID- 14966708
TI  - Daily physical activity and heart rate response in people with a unilateral
      transtibial amputation for vascular disease.
AB  - OBJECTIVE: To study the activity level and heart rate response, objectively
      measured during normal daily life, of persons with a unilateral transtibial
      amputation for vascular disease. DESIGN: Case comparison. SETTING: General
      community, daily life in the Netherlands. PARTICIPANTS: Nine subjects with a
      unilateral transtibial amputation for vascular disease (convenience sample) and 9
      control subjects without known impairments (matched for sex, age, social
      situation, employment). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Duration of dynamic activities, body motility (the intensity of body movement,
      measured with accelerometry), and heart rate (on 2 consecutive days). RESULTS:
      Persons with an amputation were less active than the comparison subjects (4.3% vs
      11.4% of a 48-h period, P=.007). Body motility during walking was lower in the
      amputee group (.111 g vs.147 g, P=.003). No differences between groups were found
      in normalized heart rate during walking. In the amputee group, a strong
      relationship was found between body motility during walking and the percentage of
      the day that the subject walked (r=.88, P=.002). No relationship was found
      between the percentage of the day that persons with an amputation were active and
      data from disability questionnaires. CONCLUSION: Persons with a unilateral
      transtibial amputation for vascular disease were considerably less active than
      persons without known impairments. Heart rate response during walking of the
      amputee group did not differ from the response in the comparison group.

PMID- 14966709
TI  - Walking stability and sensorimotor function in older people with diabetic
      peripheral neuropathy.
AB  - OBJECTIVE: To evaluate, in older people with diabetic peripheral neuropathy (DPN)
      and in age-matched controls, acceleration patterns of the head and pelvis when
      walking to determine the effect of lower-limb sensory loss on walking stability.
      DESIGN: Case-control study. SETTING: Falls and balance laboratory in Australia.
      PARTICIPANTS: Thirty persons with diabetes mellitus (age range, 55-91 y) and 30
      age-matched controls. INTERVENTIONS: Acceleration patterns of the head and pelvis
      were measured while participants walked on a level surface and an irregular
      walkway. Participants also underwent tests of vision, sensation, strength,
      reaction time, and balance. MAIN OUTCOME MEASURES: Temporospatial gait parameters
      and variables derived from acceleration signals. RESULTS: Participants with DPN
      had reduced walking speed, cadence, and step length, and less rhythmic
      acceleration patterns at the head and pelvis compared with controls. These
      differences were particularly evident when participants walked on the irregular
      surface. Participants with DPN also had impaired peripheral sensation, reaction
      time, and balance. CONCLUSIONS: Older people with DPN have an impaired ability to
      stabilize their body when walking on irregular surfaces, even if they adopt a
      more conservative gait pattern. These results provide further insights into the
      role of peripheral sensory input in the control of gait stability, and suggest
      possible mechanisms underlying the increased risk of falling in older people with
      diabetic neuropathy.

PMID- 14966710
TI  - Foot pressures during level walking are strongly associated with pressures during
      other ambulatory activities in subjects with diabetic neuropathy.
AB  - OBJECTIVE: To assess the relationship between foot pressures measured during
      level walking and other types of ambulatory activity in subjects with diabetes
      mellitus (DM) and peripheral neuropathy (PN). DESIGN: Descriptive survey with
      repeated measures. SETTING: University medical center. PARTICIPANTS: Convenience
      sample of 16 ambulatory subjects with DM and PN. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Peak pressure and pressure-time integral (PTI) at the
      heel, great toe, first metatarsal head (MT1), and third metatarsal head (MT3)
      during level walking, ramp climbing, stair climbing, and turning at a self
      selected speed. RESULTS: Peak pressure and PTI during level walking correlated
      highly with pressures during ramp climbing (r range,.85-.97) and turning (r
      range,.75-.96) at all regions examined and with pressures during stair climbing
      at MT1 and MT3 (r range,.84-.91). Correlations between pressures during level
      walking and stair climbing were moderate at the great toe (r range,.46-.57) and
      poor at the heel (r range, -.12 to -.06). With few exceptions, pressures during
      ramp climbing, stair climbing, and turning were less than (P<.008) or equal to
      pressures during level walking. We found no activity-related differences in peak
      pressure or PTI independent of the effects of preferred walking speed.
      CONCLUSIONS: Results support the clinical evaluation of peak pressure during
      level walking as an efficient method to screen for maximum levels of stress on
      the foot as patients with DM and PN perform their daily activities.

PMID- 14966711
TI  - Anticipatory postural adjustment in selected trunk muscles in post stroke
      hemiparetic patients.
AB  - OBJECTIVES: To study electromyographic characteristics of anticipatory postural
      adjustment in axial and lateral, posterior and anterior trunk muscles during the
      performance of upper-and lower-limb flexion tasks, in subjects with hemiparesis
      after stroke and to determine the relationship between anticipatory activity and
      subjects' motor and functional status. DESIGN: A nonrandomized control study.
      SETTING: Geriatric rehabilitation center in Israel. PARTICIPANTS: Fifty
      poststroke hemiparetic patients and 30 healthy control subjects. INTERVENTION:
      Electromyographic activity of the lumbar erector spinae and of the latissimus
      dorsi muscles was recorded bilaterally during flexion of either arm and from the
      2 rectus abdominis and obliquus externus muscles during flexion of either hip.
      MAIN OUTCOME MEASURES: Muscles' onset latency, cross-correlation values between
      the temporal activation profile of corresponding pairs and between ipsilateral
      muscular pairs, symmetry in activation magnitude of corresponding muscles, and
      relation between electromyographic activity and motor and functional performance
      RESULTS: Onset latencies of trunk muscles were partially delayed in the patients
      with longest hindrance displayed by the erector spinae ipsilateral to the flexing
      arm (P<.04). Temporal synchronization between pertinent muscular pairs was lower
      in the patients than in the healthy subjects, with significant group differences
      (P<.05 or lower) in the correlations between ipsilateral pairs of trunk muscles.
      Activation of the corresponding lateral trunk muscles in the patients was
      significantly less symmetrical than in the controls (P<.03 or lower) because of
      reduced activity on the paretic body side, especially on flexing of the paretic
      limbs. Conversely, in the controls as well as on the nonparetic side of the
      patients, limb flexion was associated with increased activity in the ipsilateral
      lateral trunk muscle. The erector spinae muscle in both groups and on both sides
      was more active on the contralateral side than on the ipsilateral side to the
      flexing arm. The reduced activity level in trunk muscles on the paretic body side
      was associated with deficiencies in motor and functional abilities. CONCLUSIONS:
      Major impairments in the activity of trunk muscles in hemiparetic subjects were
      manifested in the reduced activity level of the lateral trunk muscles, in delayed
      onset, and in reduced synchronization between activation of pertinent muscular
      pairs. These problems were associated with motor and functional deficits and
      warrant specific consideration during physical rehabilitation of post stroke
      hemiparetic patients.

PMID- 14966712
TI  - Reliance on visual information after stroke. Part I: Balance on dynamic
      posturography.
AB  - OBJECTIVE: To test the hypothesis that postural imbalance after stroke may be
      caused by inability to use pertinent somatosensory, vestibular, or visual
      information. DESIGN: Description of the sensory organization of patients with
      hemiplegia. SETTING: Public rehabilitation center in France. PARTICIPANTS: Forty
      patients with hemiplegia after a single hemisphere stroke who were at least 12
      months post stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The
      patients performed computerized dynamic posturography (EquiTest), which is
      designed to assess a patient's ability use sensory inputs separately and to
      effectively suppress inaccurate inputs in case of sensory conflict. Body
      stability under each of 6 sensory conditions was assessed by an equilibrium score
      (ES). RESULTS: In conditions of altered somatosensory information, with visual
      deprivation (ES5) or visuovestibular conflict (ES6), the median scores for
      patients with hemiplegia (ES5-43; ES6-20) were significantly lower than those for
      normal subjects (ES5-69; ES6-67). CONCLUSIONS: Many patients with hemiplegia seem
      to rely on visual input. The mechanism of this excessive visual reliance is
      discussed. Rehabilitation programs of postural control for the patients with
      hemiplegia should take into account the possible impairment of sensory
      organization and should include exercises to be performed under conditions of
      sensory input deprivation and sensory conflict.

PMID- 14966713
TI  - Reliance on visual information after stroke. Part II: Effectiveness of a balance
      rehabilitation program with visual cue deprivation after stroke: a randomized
      controlled trial.
AB  - OBJECTIVE: To test the hypothesis that balance rehabilitation with visual cue
      deprivation improves balance more effectively than rehabilitation with free
      vision. DESIGN: Single-blind, randomized controlled trial. SETTING: Public
      rehabilitation center in France. PARTICIPANTS: Twenty patients with hemiplegia
      after a single-hemisphere stroke that occurred at least 12 months before the
      study. INTERVENTION: Patients were randomly assigned to 1 of 2 balance
      rehabilitation programs-with and without visual cue deprivation. In all other
      respects, the programs were identical. Each lasted for 1 hour and was implemented
      5 days a week for 4 weeks. All patients completed the program. Mean outcome
      measures Balance under 6 sensory conditions was assessed by computerized dynamic
      posturography (EquiTest), gait velocity, timed stair climbing, and self
      assessment of ease of gait before and after program completion. RESULTS: After
      completing the program, balance, gait velocity, and self-assessment of gait
      improved significantly in all patients. The improvements in gait velocity (P=
      .03) and timed stair climbing (P= .01) correlated significantly with improved
      balance. Balance improved more in the vision-deprived group than in the free
      vision group. CONCLUSIONS: Balance improved more after rehabilitation with visual
      deprivation than with free vision. Visual overuse may be a compensatory strategy
      for coping with initial imbalance exacerbated by traditional rehabilitation.

PMID- 14966714
TI  - Trunk control in unstable sitting posture during functional activities in healthy
      subjects and patients with multiple sclerosis.
AB  - OBJECTIVE: To examine trunk stability in unstable sitting posture in 2 different
      functional activities. DESIGN: A randomized crossover design. SETTING:
      Rehabilitation center in Italy. PARTICIPANTS: Ten healthy subjects and 10
      patients with multiple sclerosis. INTERVENTIONS: Subjects were seated on an
      unstable support surface. A task in which the subjects had to keep their trunk as
      stable as possible was compared with tasks in which they had to track an object
      with the head or grasp an object.Main outcome measures Angular displacement and
      mean absolute angular velocity in the anteroposterior and mediolateral planes of
      the support surface. RESULTS: Angular displacement showed differences between
      patients and healthy subjects both in the sagittal plane (P<.0001) and frontal
      plane (P<.002). Velocity of angular displacement differentiated between the
      groups in both planes (P<.0001). Differences between velocity of angular
      displacement in different tasks were also detected (P<.0001). Correlation
      coefficients between sitting balance scores and laboratory measures were low and
      not statistically significant. In the healthy subjects, instability in the
      frontal plane correlated positively with the subjects' weight and height.
      CONCLUSIONS: Both patients and healthy subjects had more difficulty with frontal
      plane stability than with sagittal plane stability. Angular velocity for a given
      task showed the greatest difference between the groups and between postural
      challenge tasks within a group. Patients were more unstable than healthy subjects
      during head movements in the frontal plane; conversely, arm movements produced
      larger angular displacement, especially in the sagittal plane.

PMID- 14966715
TI  - Get up and go test in patients with knee osteoarthritis.
AB  - OBJECTIVE: To determine the reliability, minimum detectable change (MDC), and
      validity of the Get Up and Go (GUG) test. DESIGN: Repeated-measures test-retest
      for reliability. Correlational study for validity. SETTING: Institutional
      practice. PARTICIPANTS: Convenience sample of 130 people, 105 with knee
      osteoarthritis (OA) (80 women; mean age, 62+/-9 y) and 25 healthy controls (21
      women; mean age, 57+/-8 y). INTERVENTIONS: Not applicable. Main outcome measures
      Western Ontario and McMaster Universities Osteoarthritis Index, the Activity of
      Daily Living Scale of the Knee Outcome Survey, and the 8 scales of the Medical
      Outcomes Study 36-Item Short-Form Health Survey. RESULTS: Intratester and
      intertester reliability was.95 (95% confidence interval [CI],.72-.98) and.98 (95%
      CI,.94-.99), respectively. The MDC, based on measurements by a single tester and
      between testers, was 1.5 and 1.2 seconds, respectively. Time to perform the GUG
      test was longer for persons with knee OA than it was for the controls (mean
      difference, 3.3s; 95% CI, 1.8-4.9). Correlations between the GUG test and
      measures of physical function did not differ significantly from correlations
      between the GUG test and measures that do not specifically evaluate physical
      function. CONCLUSIONS: The GUG test is reliable and has an MDC that is adequate
      for clinical use. Validity of the GUG test as a single measure of physical
      function was not supported. Further research should include testing a battery of
      performance-based measures of physical function.

PMID- 14966716
TI  - The effects of home-based resistance exercise on balance, power, and mobility in
      adults with multiple sclerosis.
AB  - OBJECTIVE: To examine the effects of an 8-week home-based resistance exercise
      program on balance, power, and mobility in adults with multiple sclerosis.
      DESIGN: Experimental group design. SETTING: General community. PARTICIPANTS:
      Twenty-nine women (age, 50.3+/-8.5 y) and 8 men (age, 51.1+/-7.1 y) were
      stratified by disability level and age and were randomized into exercise (n=19)
      and control (n=17) groups. INTERVENTION: The exercise group had lower-extremity
      resistance training 3 times a week. The control group maintained current level of
      physical activity.Main outcome measures Primary outcome measures included
      balance, as measured by anteroposterior sway, mediolateral sway, and sway
      velocity using the AccuSway(PLUS) force platform; mobility as assessed with the
      Up and Go test; and leg power as assessed with the Leg Extensor Power Rig.
      RESULTS: Leg extensor power improved significantly in the exercise group
      (pretest, 3.19+/-1.36 W/kg; posttest, 3.95+/-1.23 W/kg; P=.004), although
      measures of balance and mobility did not change. CONCLUSIONS: The home-based
      resistance program was well tolerated by participants and offered a practical
      means to improve leg extensor power in a short period of time.

PMID- 14966717
TI  - An early return to vigorous activity may destabilize anterior cruciate ligaments
      reconstructed with hamstring grafts.
AB  - OBJECTIVE: To evaluate the actual date of the return to activity and its impact
      on the postsurgical stability of anterior cruciate ligament reconstruction (ACLR)
      using hamstring grafts. DESIGN: A retrospective analysis. The time of return to
      activity was determined by a questionnaire at 24 to 36 months after ACLRs.
      SETTING: An orthopedic center. PARTICIPANTS: Fifty consecutive patients who had
      ACLRs using hamstring grafts 24 to 36 months earlier. INTERVENTIONS: Not
      applicable. Main outcome measure The time of return to activity from a
      questionnaire and serial KT-2000 data at 3, 6, 12, 18, and 24 months postsurgery.
      RESULTS: Patients were divided into 2 groups according to their KT-2000 side-to
      side difference at 12, 18, and 24 months postsurgery. Group I consisted of
      patients whose differences were 3mm or less. Group II consisted of patients whose
      differences were more than 3mm. At 12 and 18 months postsurgery, significant
      differences were detected for the time of return to running and full-speed
      running. A multiple regression analysis for postsurgical stability at 24 months
      and the time of return to these 5 activities indicated that the time of return to
      full-speed running and sports activities had an effect on ACL stability.
      CONCLUSIONS: An early return to vigorous activities is not recommended in
      patients undergoing ACLRs with hamstring grafts.

PMID- 14966718
TI  - The role of knee immobilizers in cancer patients with femoral neuropathy.
AB  - OBJECTIVE: To determine the utility of knee immobilizers for cancer patients with
      femoral neuropathy. DESIGN: Retrospective case series with chart reviews and
      telephone interviews. SETTING: Teaching hospital, inpatient setting, and 1-year
      follow-up as outpatients. PARTICIPANTS: Five cancer patients with femoral
      neuropathy (4 men, 1 woman; age range, 51-76 y). Inclusion criteria were (1)
      diagnosis of femoral neuropathy, (2) receipt of knee immobilizer as an inpatient,
      and (3) ability to discuss opinions about knee orthotics at 1-year follow-up.
      INTERVENTION: Knee immobilizer. Main outcome measures Number of falls with and
      without knee immobilizer, ambulatory distance with and without immobilizer,
      subjective rating of activity level, and feeling of stability with and without
      immobilizer. RESULTS: Patients reported that the knee immobilizer reduced their
      number of falls by up to 10-fold, increased ambulatory distance between 105 and
      420 ft (31.5 and 126 m), improved their feeling of stability, and increased
      overall activity levels. CONCLUSIONS: Patients can benefit from knee immobilizers
      during their rehabilitation efforts: risk of falls decreased, ambulation distance
      increased, and relative peace of mind was achieved with the orthotic's use.

PMID- 14966719
TI  - Factors associated with prognosis of lateral epicondylitis after 8 weeks of
      physical therapy.
AB  - OBJECTIVE: To identify key factors associated with outcomes of patients who
      underwent 8 weeks of physical therapy (PT) for lateral epicondylitis. DESIGN:
      Multicenter prospective design with inception cohort of lateral epicondylitis
      patients commencing PT. Baseline clinical examinations were conducted by 1
      physical therapist; self-report outcome measures were completed at baseline and 8
      weeks later. SETTING: Nine private sports medicine clinics and 2 hospital
      outpatient departments in Ontario, Canada. PARTICIPANTS: Eighty-three patients
      with unilateral lateral epicondylitis identified by the treating physical
      therapists. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The final
      scores of the Disability of the Arm, Shoulder and Hand (DASH) questionnaire and a
      vertical pain visual analog scale (VAS) were used as the dependent variables.
      RESULTS: The final prognostic model for the 8-week DASH scores included the
      baseline score (95% confidence interval [CI], 0.34-0.66), sex (female) (95% CI,
      3.3-14.5), and self-reported nerve symptoms (95% CI, 0.8-13.8). The model for the
      8-week VAS scores included the baseline score (95% CI, 0.01-0.37), sex (female)
      (95% CI, 0.4-18.2), and self-reported nerve symptoms (95% CI, 4.7-25.5). A
      subanalysis indicated that women were more likely than men to have work-related
      onsets, repetitive keyboarding jobs, and cervical joint signs. Among women, these
      factors were associated with higher final DASH and VAS scores. CONCLUSIONS: Women
      and patients who report nerve symptoms are more likely to experience a poorer
      short-term outcome after PT management of lateral epicondylitis. Work-related
      onsets, repetitive keyboarding jobs, and cervical joint signs have a prognostic
      influence on women.

PMID- 14966720
TI  - The effect of varied fractional inspired oxygen on arm exercise performance in
      spinal cord injury and able-bodied persons.
AB  - OBJECTIVE: To examine the effect of different levels of fractional inspired
      oxygen (FiO(2)) (15%, 21%, 50%) on peak oxygen consumption (VO(2)peak) during arm
      exercise in persons with spinal cord injury and in able-bodied controls. DESIGN:
      Case-control study. SETTING: University medical center in the Netherlands.
      PARTICIPANTS: Ten able-bodied controls, 6 persons with paraplegia, and 6 persons
      with tetraplegia. INTERVENTIONS: Inspiration of 15%, 21%, and 50% oxygen during a
      15-minute period before and during arm exercise. MAIN OUTCOME MEASURES: Oxygen
      uptake (VO(2)peak, VO(2)peak/kg), power output, ventilation, and base excess.
      RESULTS: In the able-bodied controls, significant FiO(2) dependency was seen in
      power output, VO(2)peak, and VO(2)peak/kg. Persons with paraplegia showed
      significant FiO(2) dependency in VO(2) and VO(2)/kg. In persons with tetraplegia,
      no FiO(2) dependency was observed; however, VO(2) and VO(2)/kg were significantly
      higher at 50% than at 15% FiO(2). Ventilation and base excess did not change in
      able-bodied controls or in persons with paraplegia with different levels of
      FiO(2). In persons with tetraplegia, ventilation was significantly higher at 15%
      than at 50% FiO(2), and base excess did not change. No significant interactions
      between groups and FiO(2) were observed. CONCLUSIONS: Oxygen consumption during
      peak arm-cranking exercise is enhanced with an increased inspiratory oxygen
      fraction in able-bodied controls as well as in persons with paraplegia and to a
      lesser extent in persons with tetraplegia, indicating that peak oxygen
      consumption during arm exercise is limited by oxygen supply rather than by the
      small muscle mass and related biochemical limitations.

PMID- 14966721
TI  - Concurrent validity of the stroke drivers screening assessment.
AB  - OBJECTIVE: To determine the concurrent validity of the Stroke Drivers Screening
      Assessment (SDSA). DESIGN: Comparison of the SDSA with criterion standards.
      SETTING: Subjects' homes in the community in the United Kingdom. PARTICIPANTS:
      Ninety-three stroke patients (age range, 22-83y) who were referred for assessment
      of fitness to drive or who had been driving before their stroke. Participants
      were assessed a median of 5 months post stroke. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Patients were assessed on the SDSA and tests of
      visuospatial ability (Visual Object and Space Perception [VOSP] Battery),
      executive abilities (Stroop Neuropsychological Screening Test, Trail-Making Test
      [TMT], Cognitive Estimates Test [CET]), and visual memory (Recognition Memory
      Tests [RMT], Verbal Descriptions of Road Signs [VDRS]). RESULTS: The SDSA
      subtests all correlated significantly with the Stroop test (P<.001) and TMT
      (P<.001), which suggests that they measure executive abilities and attention. The
      SDSA Dot Cancellation (DC) also correlated significantly with the VDRS (P<.01).
      The SDSA Square Matrices (SM) test correlated significantly with the VOSP cube
      analysis (P< or =.01) and the RMT faces subtest (P<.001), which suggests that the
      SM test also measures visuospatial abilities and visual memory. The SDSA Road
      Sign Recognition (RSR) test also correlated significantly with the VOSP cube
      analysis (P<.05), which suggests that the RSR test also measures visuospatial
      abilities. Factor analysis produced a 2-factor solution with DC time, SM compass,
      and RSR all loading on factor 1, together with the Stroop and TMT. This factor
      was interpreted as "executive abilities and attention." The RMT faces subtest and
      CET loaded onto a second factor. CONCLUSIONS: The SDSA seems to measure
      predominantly attention and executive abilities, which have previously been shown
      to be important determinants of safety to drive. This may account for the high
      predictive validity of the SDSA.

PMID- 14966722
TI  - Reliability of maximal strength testing in older adults.
AB  - OBJECTIVES: To determine (1) the reliability of a maximal strength test (1
      repetition maximum) [1-RM] in older adults and (2) the impact of differing
      periods of familiarization. DESIGN: Within-subject, repeated trials of maximal
      strength. SETTING: Community-based senior center. PARTICIPANTS: Forty-seven
      independently living men (n=16) and women (n=31), with a mean age of 75.4+/-4.7
      years. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Systematic error (shift in
      mean) and random error (% coefficient of variation [%CV]) was assessed between
      consecutive pairs of 1-RM trials. RESULTS: For the bench press, systematic error
      was virtually eliminated for men between trials 2 and 3 (0.7%; 95% confidence
      interval [CI], -2.7% to 4.3%). The CV was stable (4.7%-7.3%) across all trials in
      both genders. For the leg press, a significant but clinically small systematic
      error (3.6%, P<.05; 95% CI, 0.8-6.6) was evident for women between trials 2 to 3.
      The CV was reduced across trial pairs by 3.3% for men and 0.9% for women. Three
      versus 6 or more sessions of familiarization produced small clinical differences
      in systematic error (< or =4.1%) and CV (< or =0.2%) between trials 2 and 3 for
      both lifts. CONCLUSIONS: Reliability is an indispensable requirement for valid
      test outcomes. Our results show that, in this group of older adults, 3
      familiarization sessions and 2 to 3 test trials produced highly reliable 1-RM
      measures. Additional periods of familiarization added little to test reliability.
      Effective reliability testing for 1-RM is a practical and attainable goal for
      outcomes based practitioners.

PMID- 14966723
TI  - The effect of foot position on the modified clinical test of sensory interaction
      and balance.
AB  - OBJECTIVES: To determine whether there was a difference in the timed scores on a
      modified version of the Clinical Test of Sensory Interaction and Balance (CTSIB)
      with the feet apart versus feet together and to correlate modified CTSIB scores
      with Sensory Organization Test (SOT) scores. DESIGN: Prospective correlational
      study. SETTING: Outpatient clinic. PARTICIPANTS: Thirty patients (mean age, 58+/
      17 y) with vestibular dysfunction who were undergoing vestibular therapy.
      INTERVENTIONS: Subjects completed the modified CTSIB with their feet together and
      feet apart at the end of a vestibular therapy session. Subjects also completed
      the SOT on the same day. MAIN OUTCOME MEASURES: Modified CTSIB scores (feet
      together, feet apart) and SOT scores. RESULTS: Modified CTSIB scores were
      slightly lower when performed with feet together as compared with feet apart.
      However, no statistically significant difference existed between scores on the
      modified CTSIB with feet together versus feet apart using the Wilcoxon signed
      rank test (P<.05). The modified CTSIB correlated more strongly with SOT scores
      when performed with feet together than with feet apart using the Spearman rho.
      CONCLUSIONS: Scores on the modified CTSIB performed with the feet together did
      not differ from scores on the modified CTSIB performed with the feet apart. In
      persons with vestibular disorders, the CTSIB done with the feet together
      correlated more closely with the SOT.

PMID- 14966724
TI  - Direct effect of percutaneous electric stimulation during gait in children with
      hemiplegic cerebral palsy: a report of 2 cases.
AB  - The feasibility of using percutaneous intramuscular functional electric
      stimulation (FES) in children with cerebral palsy (CP) as a method to improve
      ankle kinematics and kinetics during gait was investigated. Two children with
      right hemiplegic CP had percutaneous intramuscular electrodes implanted into the
      gastrocnemius and tibialis anterior muscles of the involved limb. FES was
      provided during the gait cycle using force-sensing foot switches to detect gait
      phase transitions. The children ambulated using FES under 3 conditions
      (gastrocnemius on, tibialis anterior on, gastrocnemius and tibialis anterior on).
      For each condition, two 45-minute walking sessions were conducted per day for 1
      week. Immediately after each week of practice, a gait analysis was performed at
      the subject's self-selected walking speed for that stimulation condition and
      without stimulation. Both children demonstrated improvements in ankle
      dorsiflexion angle at initial contact, peak dorsiflexion during swing, mean
      dorsiflexion during swing, and ankle work during early stance with tibialis
      anterior stimulation alone and combined gastrocnemius and tibialis anterior
      stimulation. Improvements in ankle work were found during late stance for both
      children with all stimulation conditions. These results suggest that percutaneous
      intramuscular FES was effective in improving aspects of ankle kinematics and
      kinetics of 2 children with hemiplegic CP.

PMID- 14966725
TI  - Early rehabilitation after anterior cruciate ligament reconstruction under
      regional analgesia: a case report.
AB  - Patients undergoing major knee surgery may experience postoperative pain, which
      could be exacerbated by early postoperative continuous passive motion or active
      mobilization. This pain may result in poor functional recovery. Use of regional
      analgesia techniques to achieve more consistent pain relief and to facilitate
      rapid rehabilitation can play an important role in optimizing postoperative
      outcome after anterior cruciate ligament repair (ACLR). This case study concerns
      a 20-year-old male soldier, otherwise healthy, who underwent ACLR. We inserted a
      catheter in the fascia iliaca compartment and performed postoperative analgesia
      with low-concentration ropivacaine by using an elastomeric pump. The patient
      started early rehabilitation under fascia iliaca compartment analgesia. We
      discuss the case and the influence of regional analgesia techniques on
      postoperative and clinical outcomes.

PMID- 14966727
TI  - Hepatocyte growth factor treatment ameliorates diarrhea and bowel inflammation in
      a rat model of inflammatory bowel disease.
AB  - BACKGROUND/PURPOSE: Transfection of the HLA-B27 gene into normal Fischer rats
      induces phenotypic changes similar to inflammatory bowel disease (IBD). This
      study investigated the benefits of 2 doses of hepatocyte growth factor (HGF) on
      the manifestations of IBD in this rat model. METHODS: Fischer rats and HLA-B27
      rats were divided into 4 groups: Fischer rats treated with saline, HLA-B27 rats
      treated with saline, HGF at 150 microg/kg/d, and HGF at 300 microg/kg/d. HGF or
      saline was infused for 14 days via an osmotic pump attached to a catheter in the
      internal jugular vein. After treatment, rats were evaluated for diarrhea and
      reduction in gross and microscopic bowel inflammation. Statistics were determined
      using analysis of variance (ANOVA). A P value < or =.05 was considered
      significant. RESULTS: Administration of HGF at 150 microg/kg/d decreased diarrhea
      by 40%, gross inflammation by 41%, and microscopic inflammation by 72% (P < or
      =.05). At 300 microg/kg/d HGF decreased diarrhea by 46%, gross inflammation by
      45%, and microscopic inflammation by 54% (P < or =.05). CONCLUSIONS: HGF
      administration reduces the clinical manifestations of IBD in this rat model.
      Similar effects were seen at both doses of HGF administration, implying that
      there is a plateau above which further increases in HGF levels provides no added
      benefit. HGF administration may be clinically useful in the management of IBD.

PMID- 14966728
TI  - The Isabel Forshall Lecture. Surgical management of the intersex patient: an
      overview in 2003.

PMID- 14966729
TI  - Karl Storz Lecture. Ten years of maturation of endoscopic surgery in children. Is
      the wine good?

PMID- 14966730
TI  - Inflammatory changes secondary to postoperative complications of Hirschsprung's
      disease as a cause of histopathologic changes typical of intestinal neuronal
      dysplasia.
AB  - PURPOSE: The aim of this study was to clarify the pathogenesis of intestinal
      neuronal dysplasia (IND). METHODS: The bowel habits of 36 postoperative HD
      patients were assessed retrospectively. Twenty-five had no complaints. Seven had
      persistent enterocolitis and were the focus of our study. They were divided into
      group A (n = 2) if they were severe and had associated postoperative surgical
      complications, and group B (n = 5) if they were mild. The histological changes
      were assessed. RESULTS: The 7 patients who had persistent enterocolitis
      postoperatively had no AchE activity in the mucosa, and there was normal
      distribution of submucosal and myenteric ganglia in the proximal resection
      margin. Rectal biopsies performed postoperatively for investigation of persistent
      enterocolitis in group A showed inflammatory changes and typical histopathologic
      features of IND such as abundant acetylcholinesterase (AchE)-positive nerve
      fibers in the lamina propria associated with giant submucosal ganglia and
      hyperganglionosis, and in group B there was increased AchE activity without
      hyperganglionosis or giant ganglia. CONCLUSIONS: This is the first report of
      histopathologic changes typical of IND occurring in response to persistent
      enterocolitis related to postoperative complications of surgery for HD.

PMID- 14966731
TI  - Early outcome of transanal endorectal pull-through with a short muscle cuff
      during the neonatal period.
AB  - BACKGROUND/PURPOSE: Transanal pull-through has been advocated recently for
      classic Hirschsprung's disease. The procedure leaves no scars, is associated with
      less postoperative pain and discomfort, and shortens hospital stay. Long-term
      functional outcome of patients having transanal pull-through is unclear, but
      short-term function is reported to be very similar to that after open or
      laparoscopic procedures. One-stage neonatal repair of Hirschsprung's disease has
      been suggested to be associated with less cost and demand of resources without
      jeopardizing functional outcome. The aim of this study was to ascertain the
      feasibility and safety of transanal pull-through in the neonatal period. METHODS:
      Case notes of 40 consecutive patients who had undergone transanal endorectal pull
      through for Hirschsprung's disease between January 2000 and February 2003 were
      reviewed. The patients were divided in to 3 groups: patients with neonatal
      primary pull-through (group I, 15 patients), patients operated on beyond the
      neonatal period (group II, 11 patients), and patients with a previous colostomy
      (group III, 14 patients). All colostomies except one were taken down and pulled
      through concomitantly with the transanal procedure. The case notes were evaluated
      for hospital stay, time to full oral feedings, operative and postoperative
      complications, need for postoperative dilatations, and occurrence of
      postoperative enterocolitis. RESULTS: There was no difference in median hospital
      stay (group I, 5 days; group II, 4; group III, 5) and median time to full oral
      feedings (group I, 4 days; group II, 2; group III, 3) between groups. Two
      patients (group III) had immediate postoperative prolapse of the pulled-through
      colon that was reduced without further sequels; 1 (group III) had infection of
      the stoma closure wound. Perianal skin rash that usually resolved within 6 weeks
      occurred more often in neonatal patients (group I, 10 of 15; group II: 4 of 11;
      group III: 8 of 14). Anastomotic dilatation regimen was required more often in
      neonatal cases (group I, 6 of 15; group II, 1 of 11; group III, 2 of 14).
      Enterocolitis requiring hospital care occurred in 2 patients (group I), 5 further
      patients (group II, 1; group III, 4) were treated as outpatients for symptoms
      suggesting mild enterocolitis or bacterial overgrowth. The median follow-up was 6
      months. CONCLUSIONS: Transanal endorectal pull-through in neonatal patients is as
      feasible and safe as in older children or in those with a levelling colostomy.
      However, temporary postoperative skin rash occurs more frequently in neonatal
      patients, and postoperative dilatations are required more often than in older
      children.

PMID- 14966732
TI  - Comparison of functional outcomes of Duhamel and transanal endorectal coloanal
      anastomosis for Hirschsprung's disease.
AB  - PURPOSE: The aim of this study was to determine the morbidity and medium-term
      functional outcome of the Duhamel operation and laparotomy and transanal
      endorectal coloanal anastomosis (TECA) for Hirschsprung's disease (HSCR).
      METHODS: The study populations were 34 consecutive children who underwent the
      Duhamel operation (or Lester Martin modification) and 37 who had the TECA.
      Demographic details were obtained by case note review, and functional outcome was
      determined by a combination of outpatient interview, questionnaire, and telephone
      enquiry. RESULTS: There was no difference between the groups with respect to age,
      gender, and length of aganglionic segment. Seventy percent presented as neonates
      (Duhamel, 24 of 34; TECA, 26 of 37). A single-stage primary pull-through was
      performed in 17 of 37 children in the TECA group, and in 1 of 34 from the Duhamel
      group. There was a single perioperative death in the Duhamel group and an
      unrelated, late death in the TECA group. Postoperative enterocolitis was seen in
      13 of 37 TECA children and in a single child from the Duhamel group. A stricture
      of the pull-through segment was seen in 7 of 37 children after TECA and required
      temporary diversion in 2 of 9. Late division of a rectal spur was required in 6
      of 33 Duhamel children. Requirement for late myectomy was the same in both groups
      (Duhamel 3 of 33, TECA 4 of 37). Complications requiring stoma formation occurred
      in 5 of 37 after TECA and 2 of 33 after the Duhamel operation. Two children from
      the TECA group and 1 from the Duhamel group remain diverted. One child from each
      group required a re-pull-through procedure. Two patients were lost to follow-up
      in the TECA group, leaving 34 children in this group and 33 in the Duhamel group
      in whom functional outcome could be assessed. Functional outcome was similar in
      the 2 groups. CONCLUSIONS: TECA and Duhamel procedures have similar medium-term
      functional outcomes. TECA has a high incidence of postoperative enterocolitis and
      transient stricture formation but is suitable for single-stage neonatal treatment
      of HSCR.

PMID- 14966733
TI  - Colonic transit time--what is normal?
AB  - BACKGROUND: Constipation is a common problem in childhood, and various radiologic
      methods have been advocated for investigation. Colonic transit time (CTT) has
      been used in adults to investigate colonic motility, but few studies evaluate
      this method in children. Data on CTT in the normal paediatric population are
      scarce. METHODS: The colonic transit time was measured in 22 healthy children
      (median age, 10 years; range, 4 to 15 years) by Abrahamsson's method. Children
      took bolus ingestions of radiopaque markers on 6 consecutive days, and on day 7 a
      single abdominal x-ray was performed. This was evaluated for total and segmental
      colonic transit time. RESULTS: The mean total CTT was 40 hours, and the upper
      limit of normal (95th percentile) was 84 hours. The upper limit of normal for
      segmental transit time was as follows: 14 hours for the ascending, 33 hours for
      the transverse, 21 hours for the descending, and 41 hours for the rectosigmoid
      colon. CONCLUSIONS: CTT provides an objective measure to assess childhood
      constipation. To date, 6 studies using 5 different methods have been published
      reporting values for healthy children. Comparing these, Abrahamson's method has
      low radiation exposure and is well tolerated. This study contributes additional
      normal values in children.

PMID- 14966734
TI  - Sonic hedgehog and bone morphogenetic protein 4 expressions in the hindgut region
      of murine embryos with anorectal malformations.
AB  - PURPOSE: The aim of this study was to determine the possible role of the retinoid
      mediated signaling pathway in the pathogenesis of anorectal malformations (ARM).
      The authors investigated whether all-trans retinoic acid (ATRA) affects the
      expression pattern of Sonic hedgehog (Shh) and Bone morphogenetic protein 4
      (BMP4), which play important roles in anorectal morphogenesis in vertebrates.
      METHODS: Pregnant ICR strain mice were fed 100 mg/kg of ATRA on the ninth
      gestational day (E9). Embryos with or without administration of ATRA were
      obtained from the uteri between E12 and E16 and were fixed immediately in a 4%
      paraformaldehyde solution. Frozen sections were evaluated for concentric layers
      around the endodermal epithelium by H&E and immunohistochemistry using antibodies
      created specifically to act against Shh and BMP4. RESULTS: More than 95% of the
      embryos administered ATRA had ARM; rectoprostatic urethral fistula, rectocloacal
      fistula, and short tail were the most frequent anomalies in the mouse embryos. On
      E14, normal mouse embryos had normal rectum and anus in which the epithelium of
      the anorectum was positive for Shh, and the mesenchyme was positive for BMP4. In
      the ARM embryos, however, the epithelium of the anorectum was negative for Shh,
      and the mesenchyme was also negative for BMP4. CONCLUSIONS: In normal hindgut
      development, Shh from the epithelium induces BMP4 expression in the mesenchyme,
      which differentiates into the lamina propria and the submucosa. In ARM embryos,
      expressions of Shh and BMP4 could not be found in those regions of the hindgut.
      Therefore, these findings indicate that Shh and BMP4, which appear to play a
      crucial role in organogenesis of the hindgut, were disturbed in the cell
      signaling pathway between the epithelium and the mesenchyme layers.

PMID- 14966735
TI  - Antenatal diagnosis of diaphragmatic hernia: parents' emotional and cognitive
      reactions.
AB  - PURPOSE: The aim of this study was to assess parent's emotional and cognitive
      reactions to the prenatal diagnosis of diaphragmatic hernia in their prospective
      children. METHODS: A survey was conducted by means of a questionnaire. In the
      period ranging from 1997 to 2002, 40 couples in whom an established diagnosis of
      diaphragmatic hernia was made in their fetus were seen for prenatal consultation
      at a tertiary referral center. RESULTS: Overall response rate was 93% (37
      couples). Mean period since diagnosis for compilation of the questionnaire was 2
      weeks. Mean gestational age at diagnosis was 25 weeks (range, 16 to 35 weeks).
      All parents lacked prediagnostic knowledge of diaphragmatic hernia and consider a
      single consultation with the paediatric surgeon inadequate to have a clear
      understanding of the anomaly. Only 1 mother and 1 father reported they understood
      all the information given by the surgeon. The most frequent (75%) feeling during
      and after the consultation was fear. Most parents (70%) referred to the intense
      emotions as the factor that made it difficult to follow the surgeon's
      explanations as well as to ask questions. CONCLUSIONS: Because of the
      incompatibility of emotional distress and optimum learning, impairment of early
      comprehension of information about diaphragmatic hernia is unavoidable.
      Therefore, we believe that follow-up antenatal consultations and provision of
      written and visual illustration are extremely important to facilitate informed
      choices.

PMID- 14966736
TI  - Heart energy metabolism after intestinal ischaemia and reperfusion.
AB  - BACKGROUND/PURPOSE: Multiple organ failure subsequent to intestinal ischaemia and
      reperfusion (I/R) includes cardiac failure, but little is known about heart
      energy metabolism in this setting. This study investigates the effects of
      intestinal I/R on heart energy metabolism and evaluates the effects of moderate
      hypothermia. METHODS: Adult rats underwent intestinal ischaemia for 60 minutes
      followed by 120 minutes of reperfusion. Animals were maintained at either
      normothermia (36 degrees to 38 degrees C) or moderate hypothermia (30 degrees to
      32 degrees C). In experiment A, 2 groups were studied: (1) sham at normothermia;
      (2) I/R at normothermia. After death, the heart was removed. Cardiac
      phosphoenergetics were assessed by 31P magnetic resonance spectroscopy; data are
      expressed as micromoles per gram. In experiment B, 4 groups were studied: (1)
      sham at normothermia, (2) I/R at normothermia, (3) sham at hypothermia, (4) I/R
      at hypothermia. At the end of the experiment, the heart was harvested. The
      activity of carnitine palmitoyl transferase I (CPT I), an important enzyme in the
      control of fatty acid oxidation, was measured; data are expressed as nanomoles
      per minute per unit citrate synthase. Results are expressed as mean +/- SEM.
      RESULTS: In experiment A, there were no differences between the 2 study groups in
      cardiac phosphocreatine, inorganic phosphate, adenosine triphosphate (ATP), or in
      the ratio of inorganic phosphate to ATP. In experiment B, CPT I activity was
      decreased significantly after I/R at normothermia compared with normothermic
      sham, but this enzyme inhibition was prevented by hypothermia (3.9 +/- 0.2; v
      I/R). CONCLUSIONS: These results suggest that although cardiac ATP supply was
      maintained during intestinal I/R at normothermia, the balance of substrate
      utilisation was shifted from fatty acid oxidation to carbohydrate utilisation.
      However, moderate hypothermia modified these changes. The beneficial effect of
      moderate hypothermia on cardiac metabolism during intestinal I/R has potential
      clinical application in various surgical conditions.

PMID- 14966737
TI  - Melatonin reduces oxidative stress in surgical neonates.
AB  - BACKGROUND/PURPOSE: Cytokines are inflammatory mediators found in the circulation
      after surgery. Newborns have less protection against oxidation and are very
      susceptible to free radical oxidative damage. Melatonin has been reported
      recently to reduce oxidative stress in neonates with sepsis, asphyxia, and
      respiratory distress. The aim of this study has been to determine if melatonin
      would lower interleukin (IL)-6, IL-8, tumor necrosis factor alpha (TNF-alpha) and
      nitrite/nitrate (NOx) levels and modify serum inflammation parameters, improving
      the clinical course of surgical neonates. METHODS: Ten newborns (group 1), 5 with
      surgical malformations and respiratory distress (group 1a) and 5 with isolated
      abdominal surgical malformations (group 1b) received a total of 10 doses of
      melatonin (10 mg/kg) at defined times interval for 72 hours. The treatment was
      started within 3 hours after the end of surgery. Ten surgical neonates (group 2),
      did not receive melatonin. Twenty healthy neonates (group 3) served as control.
      Blood samples were collected at the end of operation; before treatment with the
      antioxidant; and 24 hours 72 hours, and 7 days after start of treatment with
      melatonin or placebo, respectively. RESULTS: Postoperative value of cytokines and
      NOx levels of groups 1 and 2 were significantly higher than group 3. Compared
      with group 1b, group 2 displayed significantly higher cytokines and NOx levels at
      24 hours, 72 hours, and at 7 days. In group 1a the immediate postoperative values
      of cytokines were significantly higher than group 1b and group 2, but a
      significant improvement was observed after administration of melatonin with
      significantly lower levels of IL-6 and IL-8 with respect to group 2. An
      improvement of clinical outcome was observed by progressive reduction of clinical
      parameters of inflammation. CONCLUSIONS: Melatonin reduces cytokines and NOx
      levels showing potent antioxidant properties with improvement in clinical
      outcome. Further studies are warranted to define, on larger numbers, the role of
      melatonin in surgical patients.

PMID- 14966738
TI  - Surgical management of bowel perforations and outcome in very low-birth-weight
      infants (< or =1,200 g).
AB  - PURPOSE: The efficacy of peritoneal drainage (PD) as an alternative to laparotomy
      (LAP) in the management of bowel perforation (PRF) in very low-birth-weight
      infants (VLBW < or = 1,200 g) remains uncertain. The authors hypothesized that
      survival of VLBW infants with PRF depends on the severity of illness rather than
      on the initial surgical approach. METHODS: Demographic, clinical, and outcome
      data on all VLBW infants were abstracted prospectively over a 12(1/2)-year
      period. Infants with PRF were stratified by PD or by LAP. Illness acuity was
      compared using the sum of a 7-point scoring system based on the clinical signs
      determined to be of prognostic significance. The factors associated with adverse
      outcome and the epidemiology of PRF were also examined. RESULTS: Of 937 infants,
      78 with PRF required surgical intervention, consisting of PD in 32 (41%) and LAP
      in 46 (59%). Mean birth weight, illness acuity score, and the number of infants
      with NEC were significantly lower in PD (P =.0005). A higher proportion of PD
      infants received indomethacin (P =.01). There were no other differences between
      the 2 groups. Regardless of the choice of procedure, birth weight did not affect
      mortality rate; however, a shorter interval between PRF identification and
      surgical intervention was associated with improved survival rate (P =.001).
      Postoperative liver dysfunction, short gut syndrome, and enteric stricture were
      more common among LAP. Mortality rate, however, did not differ. When severe
      thrombocytopenia (P <.03) or neutropenia was present (P <.03), outcome of LAP was
      better than PD. Rescue LAP for 8 of rapidly deteriorating PD infants saved 5.
      Regardless of surgical approach, coagulopathy (P <.003), severe thrombocytopenia
      (P <.005), neutropenia (P <.0001), and multiple organ failure (P <.0001) were all
      predictive of fatality. CONCLUSIONS: Choice of surgical approach should be based
      on the underlying illness and not on birth weight. In the presence of clinical
      indication of necrotic gut, or profound abdominal infection, LAP is a better
      choice. PD, however, is far less morbid and should be considered for isolated
      PRF. Rescue LAP must be considered without delay when PD fails.

PMID- 14966739
TI  - Improved survival outcome for hepatoblastoma based on an optimal chemotherapeutic
      regimen--a report from the study group for pediatric solid malignant tumors in
      the Kyushu area.
AB  - BACKGROUND/PURPOSE: The survival outcome for patients with hepatoblastoma
      normally depends on the resectability of the tumor. In Japan, the pre and/or
      postoperative chemotherapy protocol using a combination of cisplatin (CDDP) and
      tetrahydropyranyl-Adriamycin (THP-ADR) has been the standard treatment since
      1991. This study aims to assess exactly what influence the establishment of this
      chemotherapy protocol has had on both the tumor resectability and the outcome of
      patients with hepatoblastoma. METHODS: From 1982 to 1997, 60 patients with
      hepatoblatoma were treated in the Kyushu area, Japan. Based on the pretreatment
      extent of disease (PRETEXT), the outcome and tumor resectability were compared
      between group A (1982 to 1990, n = 27, PRETEXT I:5, II:8, III:6, IV:8) and group
      B (1991 to 1997, n = 33, PRETEXT I:9, II:9, III:5, IV:10). RESULTS: The 5-year
      survival rates (group A and group B) were 33% and 73% for all cases (P <.01),
      100% and 89% for PRETEXT I, 38% and 89% for II (P <.05), 17% and 80% for III (P
      <.01), and 0% and 40% for IV (P <.01), respectively. The 5-year survival rates
      for patients with metastases were 0% for group A (n = 5) and 57% for group B (n =
      7; P <.01). The rates of a complete resection of primary tumor were 48% for group
      A and 67% for group B. In particular, a significant difference was found
      regarding the complete resection rate between groups A and B in the patients with
      PRETEXT III (17% for group A and 80% for group B; P <.01). In the patients with
      an incomplete tumor resection (14 for group A, 11 for group B), the 5-year
      survival rates were 0% for group A and 45% for group B (P <.01). CONCLUSIONS: The
      optimal chemotherapeutic regimen of CDDP and THP-ADR was thus found to greatly
      contribute to the improved survival rate of hepatoblastoma patients. Preoperative
      chemotherapy resulted in an increased resectability of the tumor, whereas
      postoperative chemotherapy played an important role in the increased cure rate of
      cases with either an incomplete tumor resection or metastasis. However,
      refractory cases with PRETEXT IV or metastasis may still require the development
      of an even more effective treatment modality, including the use of blood stem
      cell transplantation.

PMID- 14966740
TI  - Outcome and complications after resection of hepatoblastoma.
AB  - PURPOSE: The aim of this study was to review the outcome and complications after
      resection of hepatoblastoma treated over 2 decades in our institution. METHODS:
      Clinical, radiologic, and pathologic data were reviewed retrospectively, focusing
      on the outcome and complications. RESULTS: Between January 1978 and December
      2002, 56 children were treated for hepatoblastoma. The age range was 0.08 to 8.74
      years (median, 1 year). The right lobe was involved in 48%, the left lobe in 22%,
      and in 29% the main bulk of the tumour was centrally located. Surgical procedures
      included the following: hemihepatectomy in 62%, trisegmentectomy in 18%, extended
      hemihepatectomy in 16%, and liver transplantation and laparotomy in one patient
      each. Intraoperative complications occurred in 5(9%)--rupture of the tumour (1),
      haemorrhage from the contralateral lobe (1), a defect in the left hepatic duct
      (1), cardiac arrest from tumour embolus (1), and bleeding from the inferior vena
      cava (1). The mean blood loss was 280 mL (50 to 2,000 mL). Postoperative
      complications occurred in 12 patients (22%) including subphrenic abscess (3),
      adhesion obstruction (2), ischaemic stenosis of the bile duct (1), abdominal
      wound dehiscence (1), pyloric obstruction (1), and pleural effusion (2). Fifteen
      patients died, 14 as a result of tumour recurrence (mortality rate, 27%).

PMID- 14966741
TI  - Uptake of lipiodol-cytotoxics conjugates by hepatocellular carcinoma cells.
AB  - PURPOSE: The aim of this study was to quantify the uptake of anthracyclic
      cytotoxic drugs by hepatocellular carcinoma cells and the effect of Lipiodol, an
      iodinated poppy seed oil, on the uptake of anthracyclic cytotoxic conjugates by
      hepatocellular carcinoma (HCC) cells. METHODS: Monolayers of hepatocellular
      carcinoma cell line (HepG2) and a normal human hepatocyte cell line were exposed
      to 10 microg/mL doxorubicin or epirubicin with or without 2% lipiodol for 1 to 72
      hours. The fluorescence intensity in the cytospin and fixed cell were measured
      using confocal laser scanning microscope. RESULTS: The uptake of both doxorubicin
      and epirubicin by the HCC cells was mainly cytoplasmic. The mean fluorescence
      intensity at 24 hours of lipiodol-doxorubicin-treated cells was increased to 80.7
      pixel units, whereas doxorubicin-treated cells intensity was 47.9 pixel units (P
      <.05). Lipiodol did not have any effect on the uptake of epirubicin. Clonogenic
      assay confirmed a significant sensitivity difference between doxorubicin and
      epirubicin-treated hepatocellular carcinoma cell lines. CONCLUSIONS: Lipiodol has
      a selective effect on the uptake of certain cytotoxic agents. Lipiodol
      doxorubicin-targeted treatment of hepatocellular carcinoma may improve the
      intracellular uptake and hence cytotoxicity of doxorubicin in vivo.

PMID- 14966742
TI  - Wilms' tumor and horseshoe kidneys: a case report and review of the literature.
AB  - The presence of Wilms' tumor with a horseshoe kidney is an unusual combined
      clinical presentation. It has been reported that the incidence of Wilms' tumor in
      patients with horseshoe kidneys is higher than that seen in the general
      population. The current report describes a 5-year-old boy who presented with a
      stage III Wilms' tumor in a horseshoe kidney. The patient was treated with
      neoadjuvant chemotherapy followed by surgical resection, adjuvant chemotherapy,
      and radiation. The patient is disease free 40 months after diagnosis. A review of
      all reported cases of Wilms' tumor with horseshoe kidneys in the English-language
      literature before July 2002 is presented.

PMID- 14966743
TI  - The effect of a prenatal androgen disruptor, vinclozolin, on gubernacular
      migration and testicular descent in rats.
AB  - BACKGROUND/PURPOSE: Androgen has been shown to regulate inguinoscrotal testicular
      descent. This study aims to clarify the effect of one of the major endocrine
      disrupters, vinclozolin (V), on both gubernacular migration and inguinoscrotal
      testicular descent in rats. METHODS: Time-pregnant rats were segregated into 2
      groups. In group I, the rats were administered 200 mg/kg/d of V by gavage on days
      15 to 18 of gestation. In group II, the rats were administered the same volume of
      solvent and were used as controls. At birth, the anogenital distance was measured
      in pups, and gubernacular migration was examined at 10 days of age in some of
      male offspring. Next, the incidence of testicular descent and the growth of
      external genitalia were investigated in the remaining male offspring at 60 days
      of age. The chi2 test was used for statistical analysis of the results. RESULTS:
      At birth, the anogenital distance (AGD) index decreased significantly more in
      group I than in group II in male offspring. However, there was no significant
      difference in the AGD index between the 2 groups in the female offspring. At 10
      days of age, an aberrant migration of the gubernaculum was found in the 51.5% of
      V-treated rats in group I. At 60 days of age, the incidence of cryptorchidism was
      57.7% in group I and 0% in group II (P <.05). In addition, hypospadias with cleft
      phallus and pseudo vagina with a blind pouch also were observed in some of the V
      treated rats. CONCLUSIONS: Prenatal administration with V thus caused
      intrauterine defects, which resulted in testicular maldescent caused by the
      induction of an aberrant migration of the gubernaculum associated with an
      abnormal extension of the processus vaginalis, and this may have been caused by
      the antiandrogenic effect of V in utero.

PMID- 14966744
TI  - Short-time exposure to vinclozolin in utero induces testicular maldescent
      associated with a spinal nucleus alteration of the genitofemoral nerve in rats.
AB  - BACKGROUND/PURPOSE: Vinclozolin (V), a known antiandrogen, has been used widely
      to protect fruits, vegetables, and turf from fungus damage. The aim of this study
      was to clarify the effect of V on both the development of the spinal cord nucleus
      and testicular descent in rats. METHODS: Pregnant rats were administered 200
      mg/kg/d of V from day 16 to 18 of gestation. At 5 days of age, the genitofemoral
      nerve (GFN) of male pups was identified on the psoas muscle, and diamidinophenyl
      indole was applied to the proximal cut end of the GFN. Forty-eight hours later,
      the T11 to L4 level of the spinal cord was removed, and 30-microm frozen serial
      sections were made. Next, the spinal nuclei labeled in a retrograde fashion by
      diamidinophenyl indole (DAPI) were examined with a fluorescence microscope.
      Additional male pups survived until 60 days of age to evaluate the position of
      the testes. RESULTS: The size of the DAPI-labeled spinal nuclei were smaller in
      the V-treated rats than in the control rats. The average number of the DAPI
      labeled spinal nuclei decreased significantly more in the V-treated rats (176+/
      33) than in the controls (247+/- 21; P <.05) during the newborn period. At 60
      days of age, 15 of the 26 male rats showed either unilateral or bilateral
      undescended testes in the V-treated rats. The incidence of cryptorchidism was
      also significantly higher in the V-treated rats (57.7%) than in the controls (0%;
      P <.05). CONCLUSIONS: The antiandrogenic effect of the prenatal administration of
      V inhibited the development of the GFN nucleus in the spinal cord and induced
      testicular maldescent in rats. These results support the hypothesis that
      androgens regulate the descent of the testis through GFN development.

PMID- 14966745
TI  - Combined anomalies of the palate in Mohr syndrome: is preoperative
      electromyography of the palate useful?
AB  - The authors present a girl with typical characteristics of oral-facial-digital
      syndrome type II (Mohr syndrome) with a cleft soft palate and pendulous tongue
      nodules. Because of feeding difficulties, electromyography was performed of both
      morphologically identical halves of the soft palate. One half showed a normal
      muscle action potential and in the other half electrical silence was registered.
      Exploratory surgery during palatoplasty showed a fatty hamartoma in the half of
      the palate in which no electric potentials had been registered.

PMID- 14966746
TI  - Caudal duplication syndrome: more evidence for theory of caudal twinning.
AB  - Caudal duplication syndrome is a rare entity in which structures derived from the
      embryonic cloaca and notochord are duplicated to various extents. The term
      encompasses a spectrum and often is quoted as one type of incomplete separation
      of monovular twins. The authors present more evidence giving credence to caudal
      twining as the mechanism behind the syndrome. The authors report successful
      surgical management of a full-term infant with a constellation of anomalies of
      caudal duplication syndrome.

PMID- 14966747
TI  - Umbilical reconstruction after repair of large umbilical hernia: the "lazy-M" and
      omega flaps.
AB  - A simple and easy-to-perform technique of umbilical reconstruction after repair
      of a large umbilical hernia is described. Two opposing skin flaps, an upper
      inverted Omega shaped flap, and a lower, lazy M-shaped flap were designed to
      create a deep, 3-dimensional, normal-appearing umbilicus in identical twins.

PMID- 14966748
TI  - Giant cell fibroblastoma of the breast in a child--a case report and review of
      the literature.
AB  - A case report and review of the literature are reported for giant cell
      fibroblastoma of the breast in a child. This is the first reported case of a
      congenital occurrence of this tumor type (giant cell fibroblastoma).

PMID- 14966749
TI  - Needle perforation of the bowel in childhood.
AB  - Accidental ingestion of foreign bodies occurs frequently in childhood. The
      majority of them are passed spontaneously, and conservative management generally
      is recommended for foreign bodies in the stomach and duodenum. However, in some
      cases, operative intervention should be considered to prevent undesirable
      complications, such as intestinal perforation. Two cases of intestinal
      perforation owing to accidental ingestion of a needle are reported.

PMID- 14966751
TI  - Neonatal hemoperitoneum caused by a congenital liver angioma.
AB  - Severe intraabdominal bleeding in neonates within 24 hours after birth are an
      extremely seldom event. In our neonate, the intraabdominal bleeding was diagnosed
      by the clinical picture and by abdominal ultrasound examination. The etiology for
      this bleeding was primarily a blunt abdominal trauma as described in most cases
      of the liver; however, histology showed a congenital cavernous angioma of the
      liver resulting in a different tensile strength of this part of the liver in
      comparison with the rest of the liver tissue. Therefore, a relatively blunt
      abdominal trauma caused a rupture of the liver in a histologically altered part,
      which histologically was found to be a relatively soft and fragile tumor of the
      liver.

PMID- 14966752
TI  - Abdominal aplasia cutis congenita: case report and review of the literature.
AB  - A case of bilateral abdominal aplasia cutis congenita without skull defect is
      reported and was treated successfully by a combination of allografts and growth
      factors delivered by allogenic cultured keratinocytes.

PMID- 14966753
TI  - Splenic haemorrhage in a newborn as the first manifestation of wandering spleen
      syndrome.
AB  - Wandering spleen is an unusual condition in children and is even more rarely
      diagnosed in the neonatal period. A case of splenic haemorrhage after dystocic
      birth in a newborn is reported. Before surgery, results of imaging studies were
      suggestive of a ruptured spleen. On laparotomy, a big haematoma surrounding a
      wandering spleen was found. Haemorrhage aroused from short splenic arteria.
      Haemostasia and splenopexy were performed. The spleen proved later to be viable.
      The authors speculate that the haemorrhage was the first manifestation of the
      wandering spleen.

PMID- 14966754
TI  - Primary repair of tracheoesophageal fistula secondary to disc battery ingestion:
      a case report.
AB  - The authors report on a child with tracheoesophageal fistula secondary to disc
      battery ingestion. Through a low cervical collar incision with limited sternal
      split, the fistula was primarily repaired, and the omohyoid muscle and thymus
      were mobilized to cover the suture lines. There are no signs of recurrent fistula
      6 months after the operation. The anterior cervical approach with limited sternal
      split provided excellent access to the fistula. To the authors' knowledge, this
      is the first report of successful primary repair of a tracheoesophageal fistula
      secondary to disk battery ingestion.

PMID- 14966755
TI  - Pediatric surgical images. Meconium peritonitis.

PMID- 14966756
TI  - Amniotic fluid beta-endorphin: a prognostic marker for gastroschisis.

PMID- 14966757
TI  - A simple technique of laparoscopic full-thickness anterior abdominal repair of
      retrosternal (Morgagni) hernias.

PMID- 14966760
TI  - An unusual localization for an infected urachal sinus.

PMID- 14966761
TI  - Avulsion of wandering spleen after traumatic torsion.

PMID- 14966762
TI  - Inguinal hernia repair in a premature infant.

PMID- 14966763
TI  - Management of spontaneous colonic perforation in Ehlers-Danlos syndrome type IV.
AB  - A 14-year-old girl with a family history of fatal colonic rupture, presented with
      a 2-day history of abdominal pain and signs of peritonitis. At laparotomy, a full
      thickness perforation of the sigmoid colon was found, which was exteriorized as a
      loop colostomy. Subsequently, molecular studies of the patient's cultured
      fibroblasts found a point mutation in the COL3A1 gene, confirming a diagnosis of
      Ehlers-Danlos syndrome type IV (EDS-IV). Four and a half years later, a total
      abdominal colectomy and ileoproctostomy were performed, restoring intestinal
      continuity. At 5 years follow-up, the patient has had no further complications.
      Although spontaneous colonic perforation is a well-reported manifestation of EDS
      IV, a consensus on the surgical management of this complication in EDS-IV has yet
      to be determined. Given the high rate of reperforation in EDS-IV when the colon
      is left in place and the low incidence of reported small bowel and rectal
      perforations, subtotal colectomy is a reasonable treatment. Primary anastomosis
      and avoidance of an end-ileostomy was possible in this young patient, with no
      evidence of anastomotic leakage nor reperforation to date. Lifelong close follow
      up should be continued in these patients, because the natural history of this
      anatomy in EDS-IV is not known.

PMID- 14966764
TI  - Eosinophilic infiltration of the esophagus: gastroesophageal reflux versus
      eosinophilic esophagitis in children--discussion on daily practice.
AB  - BACKGROUND/PURPOSE: Children presenting with persistent symptoms attributed to
      gastroesophaeal reflux disease (GERD) that are unresponsive to both medical and
      surgical therapies are commonly submitted to esophageal biopsies, the results of
      which show an abnormal presence of eosinophils. In this setting, eosinophilic
      esophagitis may be the correct diagnosis. The purpose of this report is to
      clarify the importance of esophageal eosinophilic infiltration, regardless of
      whether associated with acid reflux, ie, as an independent symptomatic entity,
      when treating a patient with refractory GERD. METHODS: Two boys, aged 8 and 7
      years, had the classic symptoms of GERD. They were treated with antacid without
      improvement of the esophagic lesions. Subsequent esophageal biopsy results showed
      marked eosinophilic infiltration. From this moment on, eosinophilic esophagitis
      started to be considered the main diagnosis. RESULTS: Although eosinophilic
      infiltration caused by GERD is very frequently found in esophageal biopsy, in
      case of refractory drug treatment and microscopic findings of a great number of
      eosinophils and mast cells, eosinophilic esophagitis must be considered. This
      disease is better treated with corticoids instead of antacid drugs. It explains
      the reason some patients do not respond to antacid and surgical treatment and
      remain symptomatic with esophagic lesions. CONCLUSIONS: In refractory cases of
      GERD, eosinophilic esophagitis must be considered before any surgical measure.

PMID- 14966765
TI  - Volvulus of the small intestine caused by right paraduodenal hernia: a case
      report.
AB  - This report describes a very rare case of right paraduodenal hernia presenting as
      volvulus of nonherniated small intestine. A 12-year-old boy presented with sudden
      onset of lower abdominal pain, and emergency laparotomy was performed on a
      diagnosis of small intestinal obstruction. Laparotomy confirmed right
      paraduodenal hernia and volvulus of the small intestine out of the hernia sac.

PMID- 14966766
TI  - 2003: The year in heart failure.

PMID- 14966767
TI  - Implications of recent clinical trials for heart failure performance measures.

PMID- 14966768
TI  - Definition, classification, and staging of the adult cardiomyopathies: a proposal
      for revision.

PMID- 14966769
TI  - The association of 6-minute walk performance and outcomes in stable outpatients
      with heart failure.
AB  - BACKGROUND: We sought to evaluate the prognostic value of the 6-minute walk test
      in stable outpatients with heart failure. METHODS AND RESULTS: We examined the
      association of 6-minute walk test distance and outcomes among 541 patients
      enrolled in the Digitalis Investigation Group trial. Patients were grouped by
      total distance (< or =200 m, 201 m-300 m, 301 m-400 m, and >400 m) with median
      follow-up of 32 months. All-cause mortality for patients who walked < or =200 m
      was significantly higher than patients who walked >200 m (43.9% versus 23.3%,
      P<0.001), but mortality was comparable among patients who walked >200 m (201 m
      300 m: 23.7%, 301 m-400 m: 25.2%, >400 m 19.8%, P for trend 0.45). Results were
      similar for death due to worsening heart failure (< or =200 m: 29.3%, 201 m-300
      m: 7.6%, 301 m-400 m: 6.7%, >400 m: 6.1%, P for trend <0.001). In multivariable
      analysis, distance < or =200 m remained associated with increased mortality (< or
      =200 m: hazard ratio (HR) 1.47, 95% CI 0.96-2.27; >200 m: HR 1.00, Referent;
      P=0.07) and death due to worsening heart failure (< or =200 m: HR 2.89, 95% CI
      1.54-5.41; >200 m: 1.00, Referent; P=0.001). CONCLUSIONS: The 6-minute walk test
      identifies patients who walk less than 200 m as being at markedly increased risk
      of death. Changing the 6-minute walk test to a time- and distance-based standard
      would improve the efficiency of the test while retaining the bulk of the
      prognostic information.

PMID- 14966770
TI  - Peak oxygen consumption and outcome in heart failure patients chronically treated
      with beta-blockers.
AB  - BACKGROUND: Peak oxygen consumption (VO(2)) is an important criterion for listing
      patients for cardiac transplantation. Beta-blockers improve survival without
      affecting peak VO(2). We questioned the value of peak VO(2) in predicting outcome
      in patients treated with beta-blockers. METHODS AND RESULTS: We reviewed the
      records of 127 patients who had peak VO(2) measured at baseline and were
      subsequently treated with beta-blockers for at least 3 months. We divided the
      patients into 2 groups with peak oxygen consumption >14 (VO(2) hi) and < or =14
      ml.kg.min (VO(2) lo). VO(2) hi had 109 patients and VO(2) lo had 18 patients. The
      combined end-point of death or cardiac transplantation was compared between
      groups. Mean peak VO(2) and left ventricular ejection fraction were lower in
      VO(2) lo versus VO(2) hi: 12.4+/-1.4 ml.kg.min versus 19.1+/-3.9 ml.kg.min and
      17+/-8% versus 21+/-9%, respectively. At 30 months, the percentage of patients
      who did not reach the combined end-point was 94% in VO(2) lo versus 79% in VO(2)
      hi (P=.47). In multivariate analysis, only changes in heart rate and LVEF from
      baseline to follow-up were predictive of survival. CONCLUSIONS: Current peak
      VO(2) cutoff does not predict survival without transplantation of patients who
      tolerate chronic treatment with beta-blockers.

PMID- 14966771
TI  - Moderate-intensity resistance exercise training in patients with chronic heart
      failure improves strength, endurance, heart rate variability, and forearm blood
      flow.
AB  - BACKGROUND: Resistance exercise training was applied to patients with chronic
      heart failure (CHF) on the basis that it may partly reverse deficiencies in
      skeletal muscle strength and endurance, aerobic power (VO(2peak)), heart rate
      variability (HRV), and forearm blood flow (FBF) that are all putative factors in
      the syndrome. METHODS AND RESULTS: Thirty-nine CHF patients (New York Heart
      Association Functional Class=2.3+/-0.5; left ventricular ejection fraction 28%+/
      7%; age 65+/-11 years; 33:6 male:female) underwent 2 identical series of tests, 1
      week apart, for strength and endurance of the knee and elbow extensors and
      flexors, VO(2peak), HRV, FBF at rest, and FBF activated by forearm exercise or
      limb ischemia. Patients were then randomized to 3 months of resistance training
      (EX, n=19), consisting of mainly isokinetic (hydraulic) ergometry, interspersed
      with rest intervals, or continuance with usual care (CON, n=20), after which they
      underwent repeat endpoint testing. Combining all 4 movement patterns, strength
      increased for EX by 21+/-30% (mean+/-SD, P<.01) after training, whereas endurance
      improved 21+/-21% (P<.01). Corresponding data for CON remained almost unchanged
      (strength P<.005, endurance P<.003 EX versus CON). VO(2peak) improved in EX by
      11+/-15% (P<.01), whereas it decreased by 10+/-18% (P<.05) in CON (P<.001 EX
      versus CON). The ratio of low-frequency to high-frequency spectral power fell
      after resistance training in EX by 44+/-53% (P<.01), but was unchanged in CON
      (P<.05 EX versus CON). FBF increased at rest by 20+/-32% (P<.01), and when
      stimulated by submaximal exercise (24+/-32%, P<.01) or limb ischemia (26+/-45%,
      P<.01) in EX, but not in CON (P<.01 EX versus CON). CONCLUSIONS: Moderate
      intensity resistance exercise training in CHF patients produced favorable changes
      to skeletal muscle strength and endurance, VO(2peak), FBF, and HRV.

PMID- 14966772
TI  - Relation of serum levels of mast cell tryptase of left ventricular systolic
      function, left ventricular volume or congestive heart failure.
AB  - BACKGROUND: Activated mast cells (MC) present in the myocardium of patients with
      cardiomyopathy may contribute to left ventricular dilatation and systolic
      dysfunction. We sought to determine whether peripheral levels of tryptase, an MC
      specific protease, are related to indices of left ventricular size and function,
      as well as congestive heart failure (CHF) or coronary artery disease (CAD).
      METHODS AND RESULTS: Serum tryptase was measured in 85 patients undergoing
      cardiac catheterization with left ventriculography and coronary angiography and
      examined in relation to left ventricular ejection fraction (LVEF), left
      ventricular end-diastolic volume (LVEDV), congestive heart failure (CHF), and
      angiographically evident CAD. Systemic tryptase levels were lower in patients
      with increased (>90 mL) LVEDV (6.2 [5.3-8.0] mcg/L versus 8.3 [6.6-10.3] mcg/L,
      P=.01) and in patients with CHF (6.2 [3.6-7.3] mcg/L versus 8 [6.2-10] mcg/L,
      P=.02) and tended to be lower in patients with depressed (<55%) LVEF (6.8 [5.2-9]
      mcg/L versus 8 [6.3-9.9] mcg/L, P=NS). Linear regression did not show a
      significant relationship between tryptase levels with either LVEF or LVEDV.
      Finally, tryptase levels were consistently elevated in relation to the presence
      of CAD. CONCLUSION: Despite increased numbers of MC in the myocardium of patients
      with cardiomyopathy, systemic levels of MC tryptase appear to be lower in
      relation to LV systolic dysfunction, LV dilatation, or clinical CHF. In contrast,
      the presence of angiographically significant CAD is associated with elevated
      systemic tryptase levels.

PMID- 14966773
TI  - Reduced vascular compliance is associated with impaired endothelium-dependent
      dilatation in the brachial artery of patients with congestive heart failure.
AB  - BACKGROUND: Alterations in elastic properties and vascular structure of conduit
      vessels are important detrimental factors contributing to increased cardiac load
      and reduced tissue perfusion in patients with congestive heart failure (CHF). It
      has been demonstrated that endothelial function in the peripheral vasculature is
      impaired in this disorder, which may induce abnormal vascular elastic properties
      and remodeling. However, it remains unknown whether changes in vascular structure
      or mechanical properties are related to endothelial dysfunction in conduit
      arteries of patients with CHF. METHODS AND RESULTS: Twenty-five CHF patients with
      nonischemic heart disease and 20 sex/age-matched controls were enrolled. Brachial
      artery diameter, intima-media thickness (IMT), and vascular stiffness as
      represented by distensibility and compliance were determined using a high
      frequency linear transducer attached to a high-quality ultrasound system. In
      addition, flow-mediated dilatation (FMD) after 5-minute forearm occlusion and
      sublingual nitroglycerin-induced dilatation (NTG) were measured in the brachial
      artery. Brachial arterial diameter was similar between CHF and controls; however,
      IMT and wall/lumen ratio were significantly greater in CHF patients than in
      controls (IMT, 0.37+/-0.01 versus 0.31+/-0.01 mm; wall/lumen, 18.7+/-0.8 versus
      15.1+/-0.8%: both P<.01). In addition, vascular stiffness parameters were lower
      in CHF than in controls (distensibility; 1.09+/-0.14 versus 1.60+/-0.15%/kPa,
      P<.01: compliance; 0.17+/-0.02 versus 0.26+/-0.02 mm(2) kPa, P<.05). FMD and TNG
      were significantly reduced in CHF (both P<.001). Although stiffness parameters in
      CHF were not significantly correlated with vascular structure (ie, IMT,
      wall/lumen) or clinical parameters (ie, age, lipids, glucose, blood pressure),
      elastic parameters were significantly correlated with FMD (distensibility;
      r=0.579, P<.005: compliance; r=0.433, P<.05), but not with NTG. CONCLUSION: The
      present study found that, in limb muscle conduit artery in patients with CHF,
      there are hypertrophic remodeling and endothelial dysfunction-associated
      alterations in vascular wall elastic properties.

PMID- 14966774
TI  - Serial measure of cardiac troponin T levels for prediction of clinical events in
      decompensated heart failure.
AB  - BACKGROUND: This study determined whether serial determinations of cardiac
      troponin T (cTnT) in decompensated heart failure (HF) are predictive of clinical
      events (death, need for readmission for new episode of HF decompensation, or
      both) during 1 year of follow-up. METHODS AND RESULTS: Sixty-two patients with
      decompensated HF were enrolled in this cohort. The first measurement of cTnT
      (cTnT1) was from a blood sample drawn within 4 days of hospital admission; the
      second measurement (cTnT2) was on blood obtained 7 days later. Forty-nine
      clinical events (16 deaths, 10 readmissions, 23 combined readmission and deaths)
      occurred during the follow-up. The independent predictors of clinical events
      were: cTnT1>.020 ng/mL (P<.050), cTnT2>.020 ng/mL (P<.050), and serum sodium<135
      mEq/L (P<.050). Based on levels of cTnT1 and cTnT2>.020 ng/mL (+) or </=0.020
      ng/mL(-), patients were divided into 2 groups: group 1 (cTnT1-, cTnT2- or cTnT1+,
      cTnT2-), group 2 (cTnT1-, cTnT2+ or cTnT1+, cTnT2+). Group 2 patients had higher
      rates of death (45.0% versus 71.4%, P<.050), hospital readmission (35.0% versus
      61.9%, P<.050), and clinical events (55.0% versus 90.5%, P<.010) than group 1
      patients. CONCLUSIONS: Persistently increased cTnT levels (>.020 ng/mL) are
      predictive of higher rates of death and hospital readmission for decompensated
      HF.

PMID- 14966775
TI  - Prevalence and predictors of heart failure with preserved systolic function:
      community hospital admissions of a racially and gender diverse elderly
      population.
AB  - BACKGROUND: The reported prevalence of preserved systolic function (PSF) heart
      failure (HF) varies widely and has not been well-studied in nonwhite patients. To
      estimate the prevalence of PSF HF resulting in hospital admission, we studied
      admissions to a large community hospital serving a racially diverse community.
      METHODS: The charts of 300 consecutive patients > or =65 years old with a primary
      discharge diagnosis of HF were reviewed. In patients who met the Framingham
      criteria for HF diagnosis, an assessment of left ventricular function was
      obtained from review of chart data. Comparison of baseline characteristics and
      multivariate analysis of potential predictors of PSF HF was undertaken. RESULTS:
      Of the 300 patients, 247 (82%) met the Framingham criteria for diagnosis of HF.
      Ninety-seven patients (39%) of these had PSF. Twenty (8%) of the diagnosed HF
      patients had a diagnosis of severe aortic or mitral valvular disease, 9 of whom
      had preserved systolic functions. Thus 88 (36%) of the HF patients had PSF HF
      likely resulting from diastolic dysfunction. On multivariate analysis, age,
      hypertension at presentation, peripheral edema, normal sinus rhythm and a history
      of coronary artery bypass grafting or coronary angioplasty were significantly
      associated with PSF HF rather than HF with reduced systolic function. Left bundle
      branch block or other intraventricular conduction delay was independently
      associated with reduced systolic function HF. However, because these findings
      occurred in patients with and without systolic dysfunction, none were
      pathognomonic of PSF HF. CONCLUSION: In this racially diverse, majority nonwhite,
      cohort of older patients admitted for HF, the Framingham criteria for the
      diagnosis of HF were met in 82% of the patients. Of these, 39% had PSF HF and 36%
      had PSF HF in the absence of severe aortic or mitral valve disease, suggesting
      that diastolic dysfunction was etiologic. Although there was an independent
      association of PSF HF with a number of clinical characteristics, none of these
      characteristics was pathognomonic of preserved, versus reduced, systolic function
      HF.

PMID- 14966776
TI  - Mitochondria play a critical role in cardioprotection.
AB  - BACKGROUND: There is increasing evidence documenting the capacity of myocardial
      cells exposed to a variety of insults to mount a cardioprotective response.
      Although this cardioprotection has been most well characterized with respect to
      ischemic preconditioning, other chemical and metabolic stressors have been shown
      to share features of the ischemic preconditioning model, including the
      involvement of mitochondria in the triggering, signaling, and mediation of the
      cardioprotective response. METHODS: In this article, we review the evidence
      showing that mitochondria play a critical role in cardioprotection from multiple
      (often interrelated) standpoints: its primary function in producing the cellular
      bioenergetic supply, its control over events in apoptosis, its contribution to
      myocardial signal transducing processes, and its role in producing reactive
      oxidative species and in providing an appropriate antioxidant response to a
      variety of cellular insults. CONCLUSIONS: Although our understanding of
      cytoprotection has increased substantially within the last few years, the
      mechanisms mediating mitochondrial resistance to insults leading to cardiac
      protection remain to be fully delineated, and represents a significant approach
      in the clinical treatment of heart disease.

PMID- 14966777
TI  - Role of a selective aldosterone blocker in mice with chronic heart failure.
AB  - BACKGROUND: Spironolactone, a nonselective aldosterone blocker, has a
      cardioprotective effect; however, significant endocrine side effects limit its
      use. Eplerenone is a new selective aldosterone blocker. We investigated whether
      eplerenone attenuates cardiac remodeling and improves function in a mouse model
      of heart failure and whether coadministration of eplerenone and an angiotensin
      converting enzyme inhibitor (ACEi) provides better cardioprotection than either
      agent alone. METHODS AND RESULTS: C57BL/6J mice were subjected to myocardial
      infarction (MI) by ligating the left anterior descending coronary artery. Two
      weeks later, the mice were either left untreated or treated with (1) eplerenone,
      (2) ACEi, or (3) eplerenone plus ACEi for 12 weeks. Systolic blood pressure (SBP)
      was measured and echocardiography performed before MI and weekly thereafter. At
      the end of the study, interstitial collagen fraction (ICF) and myocyte cross
      sectional area (MCSA) were examined histologically. We found that (1) eplerenone
      significantly improved ejection fraction and cardiac output and decreased left
      ventricular (LV) systolic area, LV weight, ICF, and MCSA independently of changes
      in SBP compared with untreated animals; (2) ACEi had similar beneficial effects,
      accompanied by a significant reduction in SBP; and (3) combined treatment offered
      limited additional benefit beyond monotherapy. CONCLUSIONS: In mice with MI,
      eplerenone attenuates progression of heart failure comparably to ACEi, and its
      effect is independent of BP lowering.

PMID- 14966778
TI  - Valsartan-induced cardioprotection involves angiotensin II type 2 receptor
      upregulation in dog and rat models of in vivo reperfused myocardial infarction.
AB  - BACKGROUND: Cardioprotection with angiotensin II (AngII) type 1 receptor (AT(1)R)
      blockade was associated with AngII type 2 receptor (AT(2)R) upregulation and
      activation during in vivo reperfused myocardial infarction (RMI) in dogs, but it
      is unclear whether this occurs in rats. Methods and results In vivo hemodynamics,
      left ventricular (LV) function, infarct size, and AT(1)R/AT(2)R protein
      (immunoblots) after anterior RMI were measured in rats (60 minutes ischemia, 90
      minutes reperfusion, n=30) and dogs (90 minutes ischemia, 120 minutes
      reperfusion, n=22) randomized to pretreatment with valsartan (10 mg/kg,
      intravenously) or vehicle control, and vehicle sham groups. AT(1)R blockade was
      confirmed by inhibition of AngII pressor responses at the dose used. Compared
      with dog and rat controls, valsartan decreased infarct size (52 versus 31% and 47
      versus 33%, respectively), improved left ventricular ejection fraction (-32
      versus -14% and -46 versus -21%, respectively), limited infarct expansion and
      infarct thinning, and improved diastolic function after RMI. In both species,
      AT(2)R protein in the infarct zone decreased in controls and increased with
      valsartan. Sham animals showed no changes. CONCLUSIONS: AT(1)R blockade with
      valsartan induces short-term cardioprotection associated with enhanced AT(2)R
      expression in both dog and rat models of in vivo RMI.

PMID- 14966779
TI  - Dual inhibition of ACE and NEP provides greater cardioprotection in mice with
      heart failure.
AB  - BACKGROUND: Vasopeptidase inhibitors (VPi) may provide a new means of treating
      hypertension and congestive heart failure, because they simultaneously block
      angiotensin-converting enzyme (ACE) and neutral endopeptidase-24.11 (NEP-24.11),
      thereby inhibiting the renin-angiotensin system and enhancing vasodilator and
      natriuretic substances such as kinins and natriuretic peptides. METHODS: Using
      B(2) kinin receptor gene knockout mice (B(2)-/-), we tested the hypotheses that
      (1) VPi may provide better cardioprotection than ACE or NEP inhibitors alone
      (ACEi and NEPi) and (2) the effects of these inhibitors are partially mediated by
      kinins. Four weeks after myocardial infarction, B(2)-/- mice and B(2)+/+ mice
      were started on vehicle, ACEi (ramipril, 2.5 mg/kg/d), NEPi (candoxatril, 20
      mg/kg/d) or VPi (omapatrilat, 50 mg/kg/d), which was continued for 20 weeks.
      Systolic blood pressure was measured weekly and cardiac function evaluated
      monthly by echocardiography. Myocyte cross-sectional area and interstitial
      collagen fraction were measured histopathologically. RESULTS: We found that ACEi
      or NEPi improved cardiac function and remodeling and that these effects were more
      obvious in mice receiving VPi. Furthermore, the beneficial cardiac effects of
      ACEi, NEPi, and VPi were significantly attenuated in B(2)-/- mice. We concluded
      that dual inhibition of ACE and NEP with VPi provides better cardioprotection
      than ACEi or NEPi alone in mice with congestive heart failure induced by
      myocardial infarction, and these effects are mediated at least in part via
      kinins.

PMID- 14966781
TI  - A comment on COMET: how to interpret a positive trial?

PMID- 14966782
TI  - Do beta-blockers prolong survival in heart failure only by inhibiting the beta1
      receptor? A perspective on the results of the COMET trial.
AB  - Experimental and clinical studies indicate that carvedilol exerts multiple
      antiadrenergic effects in addition to beta(1)-receptor blockade, but the
      prognostic importance of these actions has long been debated. This controversy
      has now been substantially advanced by the results of the recently completed
      Carvedilol Or Metoprolol European Trial (COMET), which showed that carvedilol (25
      mg twice daily) reduced mortality by 17% when compared with metoprolol (50 mg
      twice daily), P=.0017--a result that was consistent with the differences seen
      across earlier controlled trials with beta-blockers in survivors of an acute
      myocardial infarction and in patients with chronic heart failure. Questions have
      been raised about the interpretation of these findings in view of the fact that
      the trial did not use the dose or formulation of metoprolol that was shown to
      prolong life in a placebo-controlled trial (ie, Metoprolol CR/XL [Controlled
      Release] Randomized Intervention Trial in Heart Failure). Pharmacokinetic and
      pharmacodynamic analyses, however, indicate that the dosing regimen of metoprolol
      selected for use in the COMET trial produces a magnitude and time course of
      beta(1)-blockade during a 24-hour period that is similar to the dose of
      carvedilol targeted for use in the trial. These analyses suggest that the
      observed difference in the mortality effects of metoprolol and carvedilol is not
      related to a difference in the magnitude or time course of their beta(1)-blocking
      effects but instead reflect antiadrenergic effects of carvedilol in addition to
      beta(1)-blockade.

PMID- 14966783
TI  - Selective versus nonselective beta-blockade for heart failure therapy: are there
      lessons to be learned from the COMET trial?
AB  - The recently reported COMET trial found that the beta1/beta2/alpha1 receptor
      blocking agent carvedilol given in a relatively high beta1-receptor blocking dose
      regimen was superior in mortality reduction to immediate release metoprolol given
      in a relatively low beta1-receptor blocking dose schedule. We analyze the
      problems with the trial design of COMET from the standpoint of comparing 2
      therapeutic agents at different positions on a common dose-response curve, and
      discuss the theoretical reasons why postjunctional adrenergic receptor blockade
      that is in addition to beta1-receptor antagonism will likely produce only minimal
      or no incremental benefit in chronic heart failure.

PMID- 14966784
TI  - A clinical pharmacologist's response to Dr Milton Packer's perspective on the
      results of the COMET trial.

PMID- 14966785
TI  - Beta-blockers for heart failure.

PMID- 14966786
TI  - Recovery from heart failure with circulatory assist: a working group of the
      National, Heart, Lung, and Blood Institute.
AB  - BACKGROUND: Over the past decade, mechanical circulatory support has been
      beneficial as a bridge to cardiac transplantation, and anecdotal evidence
      suggests that heart failure patients fitted with mechanical assist devices
      experience direct cardiac benefits. Moreover, recent trials on limited numbers
      and subpopulations of patients--notably the Randomized Evaluation of Mechanical
      Assistance for the Treatment of Congestive Heart Failure (REMATCH)--support
      earlier observations of improved cardiac function and point towards the use of
      assist devices as destination therapy. Methods and results To investigate this
      phenomenon, on August 2-3, 2001, the National Heart, Lung, and Blood Institute
      convened the working group, "Recovery from Heart Failure with Circulatory Assist"
      in Bethesda, Maryland. The team included cardiac surgeons, cardiologists, and
      experts in experimental research. The goal was to prioritize recommendations to
      guide future programs in: (1). elucidating the mechanisms leading to reverse
      remodeling associated with a left ventricular assist device (LVAD); (2).
      exploring advanced treatments, including novel pharmacologies, tissue
      engineering, and cell therapies, to optimize recovery with LVAD therapy; and (3).
      identifying target genes, proteins, and cellular pathways to focus on for
      production of novel therapies for myocardial recovery and cardiovascular disease.
      CONCLUSIONS: The working group also made research and clinical recommendations to
      eventually translate findings into improved therapeutic strategies and device
      design: (1). support collaborations among clinical and basic scientists with an
      emphasis on clinical/translational research that might eventually lead to
      clinical trials; (2). identify candidate patients most likely to benefit from
      LVAD as a destination therapy; (3). explore potential biomarkers indicating when
      patients could most successfully be weaned from devices; and (4). promote
      clinical and experimental study of mechanically assisted organs and the tissue
      derived from them.

PMID- 14966787
TI  - Partial reversal of cachexia by beta-adrenergic receptor blocker therapy in
      patients with chronic heart failure.
AB  - BACKGROUND: Cachexia is a common problem in chronic heart failure (CHF) that may
      be partly mediated by activation of the sympathetic nervous system. The effects
      of beta-adrenergic receptor blocker (BB) therapy on body weight in cachectic and
      noncachectic subjects with CHF has not been previously reported. METHODS AND
      RESULTS: Body weight and plasma norepinephrine, leptin, and insulin levels were
      measured in 27 subjects with CHF before and after 6 months of beta-adrenergic
      receptor blockade with carvedilol or long-acting metoprolol. Before BB therapy,
      baseline weight, plasma leptin, and plasma insulin levels did not differ between
      cachectic and noncachectic subjects. Baseline plasma norepinephrine levels were
      increased in cachectic subjects when compared with noncachectic subjects (930+/
      248 pg/mL versus 503+/-109 pg/mL, P=.063). After 6 months of BB therapy, subjects
      with baseline cachexia demonstrated significantly greater weight gain (+5.2+/-9.6
      versus +0.8+/-5.0 kg, P=.027), greater increase in plasma leptin levels (+3.7+/
      3.9 versus +1.2+/-4.3 ng/mL, P=.030), and greater decrease in plasma
      norepinephrine levels (-374+/-261 versus -41+/-122 pg/mL, P=.012) when compared
      with noncachectic subjects. CONCLUSIONS: Six months of BB therapy with carvedilol
      or long-acting metoprolol is associated with differential effects on body weight
      and hormonal levels in cachectic and noncachectic subjects with CHF. Further work
      is needed to determine the role the sympathetic nervous system in the
      pathogenesis of cachexia in patients with CHF.

PMID- 14966788
TI  - Changes in myocardial gene expression associated with beta-blocker therapy in
      patients with chronic heart failure.
AB  - BACKGROUND: The left ventricular functional recovery by beta-blocker therapy is
      now attributed to time-dependent biologic effects on cardiomyocytes. METHODS AND
      RESULTS: To elucidate the cellular mechanism of these biologic effects, we
      treated 9 patients with dilated cardiomyopathy for 4 months with beta-blockers
      and examined the gene expressions linked to an improvement of left ventricular
      ejection fraction (EF). Gene expressions of the biopsied right ventricular
      endomyocardium were assessed by real-time reverse transcription-polymerase chain
      reaction. A decrease in beta-myosin heavy chain (1.23+/-0.49 versus 0.86+/-0.45,
      P<.05) was observed 4 months after the administration of beta-blockers. The
      expression levels of both sarcoplasmic reticulum Ca(2+) ATPase (SERCA) (0.80+/
      0.28 versus 1.39+/-0.44, P<.01) and phospholamban (PLB) (0.49+/-0.08 versus
      0.88+/-0.34, P<.05) increased, whereas the expression levels of Na(+)-Ca(2+)
      exchanger (NCX), beta-adrenoreceptor kinase 1, and ryanodine receptor 2 were
      unchanged. The SERCA/NCX ratio (0.68+/-0.14 versus 0.96+/-0.33, P<.05) also
      increased. The increase in SERCA mRNA expression correlated with the degree of
      changes in EF (%deltaEF) (r=0.679, P<.05), and none of changes in these genes
      expression correlated with changes in the plasma brain natriuretic peptide
      concentration. CONCLUSIONS: The functional recovery resulting from beta-blockers
      may be associated with the restoration of the unfavorable gene expression that
      controls Ca(2+) handlings in the failing heart.

PMID- 14966789
TI  - PDE3 inhibition in dilated cardiomyopathy: reasons to reconsider.
AB  - BACKGROUND: PDE3 cyclic nucleotide phosphodiesterases have important roles in
      regulating cAMP- and cGMP-mediated signaling. Drugs that inhibit these enzymes
      raise cAMP and cGMP content in cardiac and vascular smooth muscle and increase
      the phosphorylation of proteins by cAMP- and cGMP-dependent protein kinases (PK-A
      and PK-G), thereby eliciting inotropic and vasodilatory responses. METHODS:
      Although these actions are beneficial acutely in patients with dilated
      cardiomyopathy, long-term use of these agents was shown in several clinical
      trials to increase mortality. Several new clinical studies, however, suggest PDE3
      inhibitors may be safe and effective when used in conjunction with beta
      adrenergic receptor antagonists, whereas new studies at the cellular and
      molecular levels indicate that there are several isoforms of these enzymes in
      cardiac and vascular myocytes that are likely to regulate cAMP content in
      different intracellular compartments. CONCLUSIONS: Both sets of observations
      suggest that PDE3 inhibition may be refined to allow more selective effects on
      phosphorylation of PK-A substrates, possibly allowing the beneficial effects of
      PDE3 inhibition to be separated from the adverse long-term consequences of their
      use.

PMID- 14966796
TI  - Mass spectrometry of oligosaccharides.
AB  - Glycosylation is a common post-translational modification to cell surface and
      extracellular matrix (ECM) proteins as well as to lipids. As a result, cells
      carry a dense coat of carbohydrates on their surfaces that mediates a wide
      variety of cell-cell and cell-matrix interactions that are crucial to development
      and function. Because of the historical difficulties with the analysis of complex
      carbohydrate structures, a detailed understanding of their roles in biology has
      been slow to develop. Just as mass spectrometry has proven to be the core
      technology behind proteomics, it stands to play a similar role in the study of
      functional implications of carbohydrate expression, known as glycomics. This
      review summarizes the state of knowledge for the mass spectrometric analysis of
      oligosaccharides with regard to neutral, sialylated, and sulfated compound
      classes. Mass spectrometric techniques for the ionization and fragmentation of
      oligosaccharides are discussed so as to give the reader the background to make
      informed decisions to solve structure-activity relations in glycomics.

PMID- 14966798
TI  - Biodegradable polymers from organic acids by using activated sludge enriched by
      aerobic periodic feeding.
AB  - This article describes a new process for the production of biopolymers
      (polyhydroxyalkanoates, PHAs) based on the aerobic enrichment of activated sludge
      to obtain mixed cultures able to store PHAs at high rates and yields. Enrichment
      was obtained through the selective pressure established by feeding the carbon
      source in a periodic mode (feast and famine regime) in a sequencing batch
      reactor. A concentrated mixture of acetic, lactic, and propionic acids (overall
      concentration of 8.5 gCOD L(-1)) was fed every 2 h at 1 day(-1) overall dilution
      rate. Even at such high organic load (8.5 gCOD L(-1) day(-1)), the selective
      pressure due to periodic feeding was effective in obtaining a biomass with a
      storage ability much higher than activated sludges. The immediate biomass
      response to substrate excess (as determined thorough short-term batch tests) was
      characterized by a storage rate and yield of 649 mgPHA (as COD) g biomass (as
      COD)(-1) h(-1) and 0.45 mgPHA (as COD) mg removed substrates (as COD(-1)),
      respectively. When the substrate excess was present for more than 2 h (long-term
      batch tests), the storage rate and yield decreased, whereas growth rate and yield
      significantly increased due to biomass adaptation. A maximum polymer fraction in
      the biomass was therefore obtained at about 50% (on COD basis). As for the PHA
      composition, the copolymer poly(beta-hydroxybutyrate/beta-hydroxyvalerate) with
      31% of hydroxyvalerate monomer was produced from the substrate mixture.
      Comparison of the tests with individual and mixed substrates seemed to indicate
      that, on removing the substrate mixture for copolymer production, propionic acid
      was fully utilized to produce propionylCoA, whereas the acetylCoA was fully
      provided by acetic and lactic acid.

PMID- 14966799
TI  - Biodegradation kinetics of volatile hydrophobic organic compounds in cultures
      with variable fractional volumes.
AB  - An extension of the models developed by Guha and Jaffe (Biotechnol Bioeng [1996]
      50:693-699) to describe the phenanthrene biodegradation kinetics for the cultures
      with variable fractional volumes is presented. Batch experiments were conducted
      with a culture capable of degrading the phenanthrene using a single culture
      vessel from which samples were withdrawn over time to monitor the disappearance
      of phenanthrene. For accurate measurement of phenanthrene concentrations, a
      sampling procedure designed for quantifying the sorption of phenanthrene onto
      glassware was also introduced. The Monod parameters were estimated by nonlinear
      regression analyses of simultaneous solutions to the substrate
      utilization/volatilization and Monod equations for growth of the cell mass. The
      results demonstrate that the models were able to be extended to phenanthrene
      degrading cultures with variable fractional volumes. When the ratio between
      sampling volume and volume of the culture medium was relatively small, the
      parameters obtained were similar to those which would be obtained using constant
      fractional volumes of culture medium. It was also found that the model's fit to
      the phenanthrene disappearance data in this study were better than those obtained
      by Guha and Jaffe, implying that the sorption process of phenanthrene during the
      sampling period could significantly affect the measurement of phenanthrene
      concentrations. Failing to account for these losses led to less accurate
      measurements of substrate concentrations, which in turn resulted in a poor
      estimation of the parameters. The findings of this study reduce considerably the
      experimental work necessary in the estimation of Monod kinetic parameters for the
      purpose of modeling.

PMID- 14966800
TI  - Aven and Bcl-xL enhance protection against apoptosis for mammalian cells exposed
      to various culture conditions.
AB  - A balance between proliferation and cell death is critical for achieving
      desirable high cell densities in mammalian cell culture. In this study, we
      evaluate a recently discovered anti-apoptotic gene, aven, and examine its
      effectiveness alone and in combination with a member of the Bcl-2 family, bcl-xL.
      The commercially popular cell line, Chinese hamster ovary (CHO), was genetically
      modified to constitutively express aven, bcl-xL, and the two genes in
      combination. Cells were exposed to several model insults that simulate severe
      bioreactor environments, including serum deprivation, spent medium, and Sindbis
      virus infection, as well as staurosporine, a known chemical inducer of apoptosis.
      CHO cells exhibited DNA fragmentation, a hallmark of apoptosis, after exposure to
      these model insults. After exposure to serum deprivation, 4- and 5-day spent
      medium, and staurosporine, cells expressing Aven provided limited protection
      against cell death when compared with the protection afforded by cells expressing
      Bcl-xL alone. However, the highest survival levels for all insults were achieved
      when Aven was expressed in combination with Bcl-xL. In fact, Aven appeared to act
      synergistically to enhance the protective function of Bcl-xL for several insults,
      because the protective function of the two genes expressed together in one cell
      line often exceeded the additive protective levels of each anti-apoptosis gene
      expressed alone. Surprisingly, Aven expression provided a mildly pro-apoptotic
      response in CHO isolates infected with Sindbis virus. However, CHO cells
      expressing both Bcl-xL and Aven showed protection against Sindbis virus infection
      due to the inhibitory properties of the bcl-xL anti-apoptosis gene. This study
      shows that combinatorial anti-apoptosis cell engineering strategies may be the
      most effective mechanisms for providing extended protection against cell death in
      mammalian cell culture.

PMID- 14966801
TI  - Optimized procedure for renaturation of recombinant human bone morphogenetic
      protein-2 at high protein concentration.
AB  - The human gene encoding the mature form of bone morphogenetic protein-2 (hBMP-2),
      a dimeric disulfide-bonded protein of the cystine knot growth factor family, was
      expressed in recombinant Escherichia coli using a temperature-inducible
      expression system. The recombinant protein was produced in the form of
      cytoplasmic inclusion bodies and the effect of different variables on the
      renaturation of rhBMP-2 was investigated. In particular, variables such as pH,
      redox conditions, protein concentration, temperature, the presence of different
      types of aggregation suppressors, and host cell contaminants were studied with
      respect to their effect on aggregation during refolding and on the final
      renaturation yield of rhBMP-2. It is shown that the renaturation yield is
      particularly sensitive to pH, temperature, protein concentration, and the
      presence of aggregation suppressors. In contrast, little effect of the redox
      conditions and the ionic strength on the renaturation yield was observed, as
      equal yields were obtained in a broad range of reduced to oxidized glutathione
      ratios and concentrations of NaCl, respectively. The aggregation suppressor 2
      (cyclohexylamino)ethanesulfonic acid (CHES) proved to be superior with respect to
      the final renaturation yield, although, in comparison to the more common
      arginine, it was less efficient in preventing aggregation of rhBMP-2 during
      refolding. Detergent washing of inclusion bodies was sufficient, as further
      purification of rhBMP-2 prior to refolding was without effect on the final
      renaturation yield. An increase in the concentration of renatured rhBMP-2 was
      achieved by a pulsed refolding procedure by which up to a total amount of 2.1 mg
      mL(-1) rhBMP-2 could be transferred in seven pulses into the renaturation buffer
      with an overall refolding yield of 38%, corresponding to 0.8 mg mL(-1) renatured
      dimeric rhBMP-2. Furthermore, a simplified purification procedure is presented
      that also includes freeze-drying for long-term storage of biologically active
      rhBMP-2. Finally, it is shown that the appearance of rhBMP-2 variants could be
      avoided by using a host strain overexpressing rare codon tRNAs.

PMID- 14966802
TI  - High-level secretion of functional green fluorescent protein from transgenic
      tobacco cell cultures: characterization and sensing.
AB  - Green fluorescent protein (GFP) is useful for studying protein trafficking in
      plant cells. This utility could potentially be extended to develop an efficient
      secretory reporter system or to enable on-line monitoring of secretory
      recombinant protein production in plant cell cultures. Toward this end, the aim
      of the present study was to: (1) demonstrate and characterize high levels of
      secretion of fluorescent GFP from transgenic plant cell culture; and (2) examine
      the utility of GFP fluorescence for monitoring secreted recombinant protein
      production. In this study we expressed in tobacco cell cultures a secretory GFP
      construct made by splicing an Arabidopsis basic chitinase signal sequence to GFP.
      Typical extracellular GFP accumulation was 12 mg/L after 10 to 12 days of
      culture. The secreted GFP is functional and it accounts for up to 55% of the
      total GFP expressed. Findings from culture treatments with brefeldin A suggest
      that GFP is secreted by the cultured tobacco cells via the classical endoplasmic
      reticulum-Golgi pathway. Over the course of flask cultures, medium fluorescence
      increased with the secreted GFP concentrations that were determined using either
      Western blot or enzyme-linked immunoassay. Real-time monitoring of secreted GFP
      in plant cell cultures by on-line fluorescence detection was verified in
      bioreactor cultures in which the on-line culture fluorescence signals showed a
      linear dependency on the secreted GFP concentrations.

PMID- 14966803
TI  - MIRACLE: mass isotopomer ratio analysis of U-13C-labeled extracts. A new method
      for accurate quantification of changes in concentrations of intracellular
      metabolites.
AB  - First, we report the application of stable isotope dilution theory in metabolome
      characterization of aerobic glucose limited chemostat culture of S. cerevisiae
      CEN.PK 113-7D using liquid chromatography-electrospray ionization MS/MS (LC-ESI
      MS/MS). A glucose-limited chemostat culture of S. cerevisiae was grown to steady
      state at a specific growth rate (mu)=0.05 h(-1) in a medium containing only
      naturally labeled (99% U-12C, 1% U-13C) carbon source. Upon reaching steady
      state, defined as 5 volume changes, the culture medium was switched to chemically
      identical medium except that the carbon source was replaced with 100% uniformly
      (U) 13C labeled stable carbon isotope, fed for 4 h, with sampling every hour. We
      observed that within a period of 1 h approximately 80% of the measured glycolytic
      metabolites were U-13C-labeled. Surprisingly, during the next 3 h no significant
      increase of the U-13C-labeled metabolites occurred. Second, we demonstrate for
      the first time the LC-ESI-MS/MS-based quantification of intracellular metabolite
      concentrations using U-13C-labeled metabolite extracts from chemostat cultivated
      S. cerevisiae cells, harvested after 4 h of feeding with 100% U-13C-labeled
      medium, as internal standard. This method is hereby termed "Mass Isotopomer Ratio
      Analysis of U-13C Labeled Extracts" (MIRACLE). With this method each metabolite
      concentration is quantified relative to the concentration of its U-13C-labeled
      equivalent, thereby eliminating drawbacks of LC-ESI-MS/MS analysis such as
      nonlinear response and matrix effects and thus leads to a significant reduction
      of experimental error and work load (i.e., no spiking and standard additions). By
      coextracting a known amount of U-13C labeled cells with the unlabeled samples,
      metabolite losses occurring during the sample extraction procedure are corrected
      for.

PMID- 14966804
TI  - Immobilization and biocatalytic activity of fungal protease on gold nanoparticle
      loaded zeolite microspheres.
AB  - Gold nanoparticles are excellent biocompatible surfaces for the immobilization of
      enzymes. However, separation of the gold nanoparticle-enzyme bioconjugate
      material from the reaction medium is often difficult. In this study, we
      investigate the assembly of the gold nanoparticles on the surface of the amine
      functionalized zeolite microspheres in the formation of zeolite-gold nanoparticle
      "core-shell" structures and, thereafter, the use of this structure in
      immobilization of fungal protease. The assembly of gold nanoparticles on the
      zeolite surface occurs through the amine groups present in 3
      aminopropyltrimethoxysilane (3-APTS). The fungal proteases bound to the massive
      "core-shell" structures were easily separated from the reaction medium by mild
      centrifugation and exhibited excellent reuse characteristics. The biocatalytic
      activity of fungal protease in the bioconjugate was marginally enhanced relative
      to the free enzyme in solution. The bioconjugate material also showed
      significantly enhanced pH and temperature stability and a shift in the optimum
      temperature of operation.

PMID- 14966805
TI  - Process strategies to enhance pyruvate production with recombinant Escherichia
      coli: from repetitive fed-batch to in situ product recovery with fully integrated
      electrodialysis.
AB  - Using the pyruvate production strain Escherichia coli YYC202 ldhA::Kan different
      process alternatives are studied with the aim of preventing potential product
      inhibition by appropriate product separation. This strain is completely blocked
      in its ability to convert pyruvate into acetyl-CoA or acetate, resulting in
      acetate auxotrophy during growth in glucose minimal medium. Continuous
      experiments with cell retention, repetitive fed-batch, and an in situ product
      recovery (ISPR) process with fully integrated electrodialysis were tested.
      Although the continuous approach achieved a high volumetric productivity (QP) of
      110 g L(-1) d(-1), this approach was not pursued because of long-term production
      strain instabilities. The highest pyruvate/glucose molar yield of up to 1.78 mol
      mol(-1) together with high QP 145 g L(-1) d(-1) and high pyruvate titers was
      achieved by the repetitive fed-batch approach. To separate pyruvate from
      fermentation broth a fully integrated continuous process was developed. In this
      process electrodialysis was used as a separation unit. Under optimum conditions a
      (calculated) final pyruvate titer of >900 mmol L(-1) (79 g L(-1)) was achieved.

PMID- 14966806
TI  - Hyperactivation of Rhizomucor miehei lipase by hydrophobic xerogels.
AB  - Although a variety of approaches exist for the immobilization of enzymes, the
      "science" of enzyme immobilization is still in its infancy. In recent years,
      considerable interest has developed regarding the use of xerogels for enzyme
      immobilization. There are several advantages to xerogels for enzyme
      immobilization, including the opportunity to produce them in defined shapes or
      thin films and the ability to manipulate their physical characteristics (e.g.,
      porosity, hydrophobicity, and optical properties). In this study we examined the
      effect of xerogel hydrophobicity on the activity of lipase (EC 3.2.2.3) from
      Rhizomucor miehei. The hydrophobicity of the xerogels was manipulated by
      generating xerogels with various molar ratios of propyltrimethoxysilane (PTMS) to
      tetramethoxysilane (TMOS), from 1:1 to 10:1. The belief was that, by increasing
      the proportion of propyl groups, the hydrophobicity of the resulting xerogel
      would be increased. Differences in the hydrophobicity of the resulting xerogels
      were confirmed using water-affinity studies. Two approaches were taken for water
      affinity determinations by examining the ability of the xerogels to remove water
      from air (controlled humidity) and from water-saturated isopropyl ether. Xerogels
      with higher propyl content showed a reduced affinity for water. A crude lipase
      preparation from Rhizomucor miehei was then contacted with sized xerogel
      particulates and the effect of the xerogel on lipase activity was determined. The
      presence of the xerogel resulted in hyperactivation of the lipase. Analysis of
      the protein adsorption revealed changes in the profile of proteins adsorbed to
      the xerogel based on the hydrophobicity of the xerogel. Based on estimations of
      the specific activity of the hyperactivated lipase, a minimum hyperactivation of
      207% was observed. Part of the hyperactivation may be attributable to xerogel
      lipase interactions, but also to the adsorption of a component from the crude
      lipase preparation that may complex with the lipase and the xerogel producing a
      stabilizing effect. Further improvements in hyperactivation and selectivity of
      the xerogels is likely possible by working at lower PTMS:TMOS ratios than those
      investigated in this study.

PMID- 14966807
TI  - Hollow fiber bioreactor: new development for the study of contrast agent
      transport into hepatocytes by magnetic resonance imaging.
AB  - The aim of our study was to develop a magnetic resonance (MR)-compatible in vitro
      model containing freshly isolated rat hepatocytes to study the transport of
      hepatobiliary contrast agents (CA) by MR imaging (MRI). We set up a perfusion
      system including a perfusion circuit, a heating device, an oxygenator, and a
      hollow fiber bioreactor (HFB). The role of the porosity and surface of the hollow
      fiber (HF) as well as the perfusate flow rate applied on the diffusion of CAs and
      O2 was determined. Hepatocytes were isolated and injected in the extracapillary
      space of the HFB (4 x 10(7) cells/mL). The hepatocyte HFB was perfused with an
      extracellular CA, gadopentetate dimeglumine (Gd-DTPA), and gadobenate dimeglumine
      (Gd-BOPTA), which also enters into hepatocytes. The HFB was imaged in the MR room
      using a dynamic T1-weighed sequence. No adsorption of CAs was detected in the
      perfusion system without hepatocytes. The use of a membrane with a high porosity
      (0.5 microm) and surface (420 cm2), and a high flow rate perfusion (100 mL/min)
      resulted in a rapid filling of the HFB with CAs. The cellular viability of
      hepatocytes in the HFB was greater than 85% and the O2 consumption was maintained
      over the experimental period. The kinetics of MR signal intensity (SI) clearly
      showed the different behavior of Gd-BOPTA that enters into hepatocytes and Gd
      DTPA that remains extracellular. Thus, these results show that our newly
      developed in vitro model is an interesting tool to investigate the transport
      kinetics of hepatobiliary CAs by measuring the MR SI over time.

PMID- 14966808
TI  - Application of Plackett-Burman design and response surface methodology to achieve
      exponential growth for aggregated shipworm bacterium.
AB  - Here we report the successful implementation of the Plackett-Burman
      multifactorial design to screen the limiting components for growth and subsequent
      use of the response surface methodology (RSM) to design a medium that supported
      exponential growth of the aggregated morphology of the shipworm bacterium,
      Teredinobacter turnirae. The results obtained with the help of Plackett-Burman
      design indicated limitations of three components in the growth medium,
      MnCl2.4H2O, Na2CO3, and K2HPO4. The concentrations of these three components were
      further optimized using RSM. By increasing the concentrations of the above
      mentioned components by 4-fold, 12-fold, and 12-fold, respectively, it became
      possible to achieve exponential growth of the culture.

PMID- 14966809
TI  - Pediocin production by Pediococcus acidilactici in solid state culture on a waste
      medium: process simulation and experimental results.
AB  - The production of pediocin by Pediococcus acidilactici was comparatively studied
      in submerged and solid-state culture, using polyurethane foam particles soaked in
      commercial (MRS) and waste media with various supplements, where product
      concentrations were 15 times higher in MRS medium. For the solid state analysis,
      cultures were treated by successive compression and refilling of tubular
      minireactors equipped with a piston, without the need for reinoculation. This
      method was found to be simple, reproducible, and easily controllable, allowing
      culture productivity to be maintained for long periods of time without
      alterations in the basic properties of the system. In addition, yields were found
      to be superior compared to those from submerged culture. The system kinetics were
      modeled on the basis of widely accepted assumptions with a good fit to the
      experimental results and observed biomass fluctuations less evident than those
      predicted by the kinetic model.

PMID- 14966810
TI  - Chemical inhibition of nitrification in activated sludge.
AB  - Conventional aerobic nitrification was adversely affected by single pulse inputs
      of six different classes of industrially relevant chemical toxins: an
      electrophilic solvent (1-chloro-2,4-dinitrobenzene, CDNB), a heavy metal
      (cadmium), a hydrophobic chemical (1-octanol), an uncoupling agent (2,4
      dinitrophenol, DNP), alkaline pH, and cyanide in its weak metal complexed form.
      The concentrations of each chemical source that caused 1 5, 25, and 50%
      respiratory inhibition of a nitrifying mixed liquor during a short-term assay
      were used to shock sequencing batch reactors containing nitrifying conventional
      activated sludge. The reactors were monitored for recovery over a period of 30
      days or less. All shock conditions inhibited nitrification, but to different
      degrees. The nitrate generation rate (NGR) of the shocked reactors recovered
      overtime to control reactor levels and showed that it was a more sensitive
      indicator of nitrification inhibition than both initial respirometric tests
      conducted on unexposed biomass and effluent nitrogen species analyses. CDNB had
      the most severe impact on nitrification, followed by alkaline pH 11, cadmium,
      cyanide, octanol, and DNP. Based on effluent data, cadmium and octanol primarily
      inhibited ammonia-oxidizing bacteria (AOB) while CDNB, pH 11,and cyanide
      inhibited both AOB and nitrite-oxidizing bacteria (NOB). DNP initially inhibited
      nitrification but quickly increased the NGR relative to the control and
      stimulated nitrification after several days in a manner reflective of oxidative
      uncoupling. The shocked mixed liquor showed trends toward recovery from
      inhibition for all chemicals tested, but in some cases this reversion was slow.
      These results contribute to our broader effort to identify relationships between
      chemical sources and the process effects they induce in activated sludge
      treatment systems.

PMID- 14966811
TI  - Effect of PM10 pollution in Bangkok on children with and without asthma.
AB  - This study aimed to investigate the effects of PM10 concentrations exceeding the
      Thai national standard (24-hr average, >120 microg/m3) on daily reported
      respiratory symptoms and peak expiratory flow rate (PEFR) of schoolchildren with
      and without asthma in Bangkok. The 93 asthmatic and 40 nonasthmatic
      schoolchildren were randomly recruited from a school located in a highly
      congested traffic area. Daily respiratory symptoms and PEFR of each child were
      evaluated and recorded in the diary for 31 successive school days. During the
      study period, 24-hr average PM10 levels ranged between 46-201 microg/m3. PM10
      levels exceeded 120 microg/m3 for 14 days. We found that when PM10 levels were
      >120 microg/m3, the daily reported nasal irritation of asthmatic children was
      significantly higher than when PM10 levels were < or =120 microg/m3. In addition,
      when PM10 levels were >120 microg/m3, nonasthmatic children had a significantly
      higher daily reported combination of any respiratory symptoms. PEFR did not
      change with different ambient PM10 levels in both groups. This study suggests
      that elevated levels of PM10 concentrations in Bangkok affect respiratory
      symptoms of schoolchildren with and without asthma.

PMID- 14966812
TI  - Is clinical wheezing reliable as the endpoint for bronchial challenges in
      preschool children?
AB  - The present study was designed to compare the clinical finding of wheeze by
      auscultation with an objective evaluation by acoustic means at the endpoint of a
      bronchial challenge in preschool children. Challenges were undertaken using a
      tidal breathing method in 51 preschool children as part of the investigation of
      possible asthma. An electronic stethoscope was used for auscultation of each lung
      and for the simultaneous recording of the acoustic sonogram for analysis. In 24
      children, the pediatrician determined that the challenge was positive, and in 22
      of these, he heard wheezing at the endpoint of the challenge. In 2 children the
      challenge was considered positive, based on a modest fall in saturation. The
      acoustic record was scanned manually for presence of wheeze defined in terms of
      duration, and power spectrum without reference to auscultatory findings. In
      positive challenges, the mean wheeze rate was 28.1% (95% CI, 19.5-36.8%), while
      no wheeze was detected acoustically in negative challenges. Using a cutoff wheeze
      rate (duration of wheeze/duration of breath phase x100) of 10% for the whole
      group, clinical wheezing detected by the pediatrician had a sensitivity of 100%
      (no false negatives) and a specificity of 91%. In conclusion, the clinical
      observation of wheeze agrees very well with its detection by acoustic measurement
      at the endpoint of a bronchial challenge in preschool children.

PMID- 14966813
TI  - Risk factors for an intensive care unit admission in children with asthma.
AB  - An admission to an intensive care unit (ICU) with asthma is a marker of asthma
      severity and may be a precursor of asthma death. The aim of this study was to
      investigate risk factors for acute severe asthma needing an ICU admission. We
      hypothesized that children admitted to the ICU represent a severe phenotype with
      identifiable premorbid clinical features. The study was case-control in design.
      One hundred and forty-one children were studied. Seventy children admitted to the
      ICU and 71 children admitted to the general medical ward served as cases and
      controls, respectively. Children were aged between 1-16 years. They underwent
      skin prick allergy testing, and had a nasopharyngeal aspirate and serology
      performed to screen for respiratory pathogens. Their parents completed an asthma
      and allergy symptom questionnaire and the Newcastle Asthma Knowledge
      Questionnaire (NAKQ). On univariate analysis, an admission to the ICU was more
      likely in children with 1) "frequent episodic" or "persistent" background asthma;
      2) three or more previous admissions for asthma; 3) one or more asthma admissions
      in the previous 12 months; 4) three or more presentations to the Emergency
      Department (ED) in the preceding 12 months; 5) three or more positive responses
      on skin prick allergy testing; 6) an elevated IgE level; 7) oxygen saturation on
      presentation < or =91%; 8) longer duration of asthma; 9) lower level of maternal
      education; 10) an admission during autumn; 11) three or more siblings; and 12)
      being prescribed antibiotics. Risk factors that remained significant on
      multivariate analysis were three or more presentations to the ED in the preceding
      12 months (P=0.003), an elevated IgE level (P=0.01), oxygen saturation on
      presentation < or =91% (P=0.003), and longer asthma duration (P=0.02). ICU
      patients took longer to see a doctor and to commence oral steroids. No
      differences were found between cases and controls in the proportion taking
      preventer therapy (58% vs. 52%), provided with a written asthma action plan (32%
      vs. 25%), or in whom spirometry or peak flow was measured (28% vs. 42%). However,
      rates were low in both groups. Parental asthma knowledge was generally poor. This
      study identified risk factors for an ICU admission in children with asthma. A
      potentially preventable risk factor is a history of multiple ED presentations in
      the past year. Specialist referral of children with multiple ED presentations may
      improve asthma control and reduce the risk of an ICU admission. Background asthma
      management remains suboptimal in children needing hospitalization.

PMID- 14966814
TI  - Perceptions of value of routine care among patients with cystic fibrosis and
      their families.
AB  - Routine quarterly visits are an integral part of effective disease management for
      patients with cystic fibrosis (CF), regardless of the patient's age. The
      objective of this study was to explore the relationship between perceptions of
      the value of routine visits and perceived overall quality of care. The population
      in this study consisted of 194 patients at a single CF center. Telephone
      interviews were completed with 162 parents of children or adult patients
      (response rate, 84%) in May-June 2000. Among other satisfaction-related
      questions, respondents were asked to rate: 1) overall quality of care, 2)
      importance of routine clinic visits in providing good preventative care, and 3)
      helpfulness of routine clinic visits in providing knowledge for CF care. They
      were also asked open-ended questions concerning the reasons for their ratings.
      Perceived helpfulness and importance of routine visits were negatively associated
      with patient age and positively associated with perceived overall quality of
      care, especially for parents of teenage patients. The most common reason for low
      importance ratings was that the patient's health is perceived to be good, making
      routine clinic visits unnecessary. The most common reasons for low helpfulness
      ratings were that the visits are too repetitive or routine, and the family learns
      nothing new from them. In conclusion, tailoring routine visits to respond to
      different age-based needs and making routine visits less repetitive may add value
      to routine visits, which could result in increased perceived overall quality of
      care, especially for parents of teenage patients.

PMID- 14966815
TI  - Epidemiologic survey of 196 patients with congenital central hypoventilation
      syndrome.
AB  - This study examined the cross-sectional medical and social characteristics of
      children diagnosed with congenital central hypoventilation syndrome (CCHS). A
      detailed questionnaire was mailed to all families with a child with CCHS who are
      affiliated with a family network or support group. The questionnaire response
      rate was >75% (n=196). Mean age was 10.22 years +/- 6.6 years (SD) (range, 0.4-38
      years), with a 1:1 sex ratio. Multisystem involvement was almost universal among
      the cohort, with Hirschsprung's disease (HD) present in 16.3%; 61.7% of the
      children had a tracheotomy, but 14.3% were never tracheotomized, with 77 subjects
      (39.3%) not having a tracheostomy tube at time of survey. Respiratory support
      approaches varied but clearly reflected the trend towards earlier and more
      widespread transition to noninvasive ventilatory modalities. Significant
      developmental problems were noted, but attendance in regular classes occurred in
      the majority. Significant deficiencies in routine periodic evaluation and
      management were reported. In addition, the presence of CCHS was associated with a
      significant financial and psychosocial burden to the families. In conclusion, a
      comprehensive survey of 196 CCHS children and their families revealed a cross
      sectional picture of substantial medical and psychosocial complexities associated
      with this disorder, and pointed out substantial inadequacies in routine
      preventive care that appear to impose stress on the families. The emerging trend
      of earlier transition to noninvasive ventilatory support warrants future studies.
      Implementation of recommended guidelines for diagnosis and multidisciplinary
      follow-up of CCHS should ultimately ameliorate the long-term outcome of this
      lifelong condition.

PMID- 14966816
TI  - Internal mandibular distraction to relieve airway obstruction in infants and
      young children with micrognathia.
AB  - Micrognathia may cause upper airway obstruction requiring complex medical
      interventions and sometimes tracheostomy. The role of distraction techniques to
      lengthen the mandible is yet to be clarified. The aim of this paper is to present
      a series of five cases in which mandibular lengthening by osteotomy and internal
      distraction was used to relieve airway obstruction. Five patients whose ages
      ranged from 4-39 months (mean, 15 months) were managed at our center with
      internal distraction osteogenesis to relieve airway obstruction. Three patients
      had a tracheostomy, and two patients had refractory airway obstruction prior to
      distraction. Following osteotomy and insertion of internal distraction devices,
      the mandible was distracted a mean of 17 mm (range, 15-25 mm). The distraction
      devices were removed at the end of a consolidation period ranging from 3-10
      weeks. Two of 3 patients with a tracheostomy were decannulated, while the third
      patient with tracheostomy is awaiting choanal atresia repair before being
      decannulated. The two patients who were not managed with a tracheostomy but who
      had persistent upper airway obstruction have not required further airway
      intervention after mandibular distraction. In conclusion, mandibular lengthening
      by distraction osteogenesis can relieve airway obstruction in infants and small
      children. This is a promising new technique that may avoid the need for
      tracheostomy in some infants with micrognathia, and facilitate early
      decannulation in those who have a tracheostomy.

PMID- 14966817
TI  - Pulmonary function in bronchopulmonary dysplasia.
AB  - The purpose of this study was to examine lung function and bronchodilator
      responsiveness in infants with a history of prematurity and bronchopulmonary
      dysplasia (BPD), using the raised volume rapid thoracoabdominal compression
      technique as well as with whole-body plethysmography. Spirometric measurements
      were obtained in 28 infants with a history of BPD, defined as preterm birth with
      O2 requirement at 36 weeks postmenstrual age (gestational age at birth, 26.4 +/-
      2.1 weeks, mean +/- SD; birthweight, 898 +/- 353 g; age at study, 68.0 +/- 35.6
      weeks). Fractional lung volumes were measured in 27 subjects. Values were
      expressed as percentage of predicted normal values. Compared to normal infants,
      those with a history of BPD exhibited decreases in forced expiratory flows
      including forced expiratory volume in 0.5 sec (76.3 +/- 19.6%), forced expiratory
      flow at 75% of expired forced vital capacity (FEF75; 59.5 +/- 30.7%), and FEF(25
      75) (74.0 +/- 26.8%; P<0.01 for all). Functional residual capacity (107.9 +/-
      25.3%), residual volume (RV, 124.5 +/- 42.7%), and RV/total lung capacity
      (RV/TLC, 128.2 +/- 35.3%) were increased in infants with a history of BPD (P<0.05
      for each). There was no difference in TLC between groups. Seventeen infants were
      studied both pre- and postalbuterol, and 6 (35%) demonstrated significant
      bronchodilator responsiveness. Infants with recurrent wheezing showed greater
      expiratory flow limitation, hyperinflation, and airways responsiveness, whereas
      those without wheezing showed only modest airway dysfunction. We conclude that
      infants with a history of BPD have pulmonary function abnormalities characterized
      by mild to moderate airflow obstruction and air trapping.

PMID- 14966818
TI  - Use of a respiratory clinical score among different providers.
AB  - Respiratory assessment of children with asthma or bronchiolitis is problematic
      because both the components of the assessment and their relative importance vary
      among care providers. Use of a systematic standard assessment process and
      clinical score may reduce interobserver variation. Our objective was to determine
      observer agreement among physicians (MD), nurses (RN), and respiratory therapists
      (RT), using a standard respiratory clinical score. A clinical score was developed
      incorporating four physiologic parameters: respiratory rate, retractions,
      dyspnea, and auscultation. One hundred and sixty-five provider pairs (e.g., MD
      MD, RN-RT) independently assessed a total of 55 patients admitted for asthma,
      bronchiolitis, or wheezing at an urban tertiary-care hospital. A weighted kappa
      statistic measured agreement beyond chance. Rater pairs had high observed
      agreement on total score of 82-88% and weighted kappas ranging from 0.52 (MD-RN;
      95% CI, 0.19, 0.79) to 0.65 (RN-RN; 95% CI, 0.46, 0.87). Observed agreement on
      individual components of the score ranged from 58% (auscultation) to 74%
      (dyspnea), with unweighted kappas of 0.36 (respiratory rate; 95% CI, 0.26, 0.46)
      to 0.53 (dyspnea; 95% CI, 0.41, 0.65). In conclusion, this respiratory clinical
      score demonstrates good interobserver agreement between MDs, RNs, and RTs. Future
      research is needed to examine validity and responsiveness in clinical settings.
      By standardizing respiratory assessments, use of a clinical score may facilitate
      care coordination by physicians, nurses, and respiratory therapists and thereby
      improve care of children hospitalized with asthma and bronchiolitis.

PMID- 14966819
TI  - Upregulation of endothelial nitric oxide synthase and endothelin-1 in pulmonary
      hypertension secondary to heart failure in aorta-banded rats.
AB  - This study assessed alterations in expression of pulmonary endothelial nitric
      oxide synthase (eNOS) and endothelin-1 (ET-1) in rats with pulmonary hypertension
      (PH) after the ascending aorta had been banded. Rats were studied 12 weeks after
      banding, which resulted in left heart failure with elevated pulmonary arterial
      pressure (banded: 31.3 +/- 5.9 (mean +/- SD) mmHg; sham: 20.0 +/- 4.7 mmHg,
      P<0.05). Competitive reverse transcription-polymerase chain reaction demonstrated
      significant increases in pulmonary expression of preproET-1 mRNA and eNOS mRNA.
      Western blot analysis indicated increased pulmonary eNOS protein.
      Radioimmunoassays indicated increased plasma ET-1 concentrations in the pulmonary
      artery (banded: 12.4 +/- 1.5 pg/ml; sham: 9.0 +/- 1.3 pg/ml, P<0.01) and
      increased ET-1 content in lungs (banded: 240 +/- 21 ng/g protein; sham: 203 +/-
      20 ng/g protein, P<0.05). There was increased immunohistochemical staining of
      eNOS and ET-1 in the pulmonary vascular endothelium of aorta-banded rats. Even in
      the presence of increased eNOS expression, it was not clear how nitric oxide (NO)
      production (decreased, unchanged, or increased) was involved in the compensatory
      mechanism to offset pulmonary vasoconstriction. Increased ET-1 expression may be
      important in mediating PH secondary to aortic banding, and may offer insights
      into the use of ET-1 antagonists in treating patients with PH secondary to heart
      failure.

PMID- 14966820
TI  - Thoracic wall lesions in children.
AB  - Our objective was to review the clinical features and radiographic manifestations
      of chest wall lesions in a pediatric chest unit. Twenty-five patients (11 males
      and 14 females, aged 14 months to 15 years) were suspected of having a chest wall
      lesion on the basis of clinical examination and chest radiograph. A retrospective
      review of clinical characteristics and radiographic findings was performed in
      order to define the pathology and extent of lesions and outcomes of chest wall
      diseases in children. Thirty-six percent of pediatric patients studied for
      thoracic abnormalities had anatomical variations of the thoracic cage such as
      sternal titling, bifid ribs, and costal cartilage convexities. Tuberculous
      infections of the sternum and ribs were seen in 4 cases. Osteochondromas were
      seen in 4 patients, and were especially noted in patients with a history of
      familial exostosis. Other malignant thoracic wall tumors included in this study
      included chondrosarcoma (n=1), Ewing's sarcoma (n=1), and primitive
      neuroectodermal tumor (n=2). In conclusion, the protruding lesions arising from
      the chest wall demonstrate a wide range of normal, congenital variant, and
      pathologic lesions arising from the soft tissues and bony components. Those with
      life-threatening lesions (less likely located in the parasternal region) are more
      prone to have chest pains and dyspneic respirations; in most cases, plain chest
      radiographs tend to have a high rate of bony or pleural involvement as well as
      thoracic deformities. In an endemic area of tuberculosis, costal tuberculosis
      should be considered in undiagnosed bony lesions; a chest CT scan could be
      diagnostically useful.

PMID- 14966821
TI  - Efficacy and safety of ipratropium bromide plus fenoterol inhaled via Respimat
      Soft Mist Inhaler vs. a conventional metered dose inhaler plus spacer in children
      with asthma.
AB  - The objective of this study was to compare the efficacy and safety of ipratropium
      bromide/fenoterol hydrobromide (IB/FEN; Berodual) delivered from the novel
      propellant-free Respimat Soft Mist Inhaler (SMI) with that from a
      chlorofluorocarbon (CFC) metered-dose inhaler (MDI) plus spacer in children with
      asthma. The study followed a multicenter, randomized, double-blind (within
      Respimat SMI), parallel-group design. During the 2-week run-in period, patients
      received two actuations of CFC-MDI tid (IB 20 microg/FEN 50 microg per actuation)
      via a spacer (Aerochamber) (MDI 40/100). Patients (n=535) were then randomized
      to: Respimat SMI containing IB 10 microg/FEN 25 microg (Respimat SMI 10/25), IB
      20 microg/FEN 50 microg (Respimat SMI 20/50), one actuation tid or CFC-MDI
      containing IB 20 microg/FEN 50 microg per actuation (in total 1B 40 microg/FEN
      100 microg), or two actuations tid via Aerochamber (MDI 40/100), for 4 weeks. The
      primary endpoint was the change in forced expiratory volume in 1 second (FEV1)
      during the first 60 min after dosing (area under the curve from 0-1 h [AUC(0-1
      h)]) on day 29. Analysis of the primary endpoint demonstrated that the efficacy
      of Respimat SMI 10/25 and 20/50 was equivalent to or greater than that of MDI
      40/100. Similar results indicating that Respimat SMI 10/25 and 20/50 were not
      inferior to MDI 40/100 were also found on days 1 and 15. Analyses of other
      secondary endpoints supported these results. The safety profile of Respimat SMI
      was comparable to that of the CFC-MDI plus spacer. In conclusion, IB/FEN
      delivered via Respimat SMI is at least as effective as, and is as safe as, when
      delivered via CFC-MDI plus Aerochamber in children with asthma. Use of Respimat
      SMI thus enables a 2-4-fold reduction in the nominal dose of IB/FEN, and obviates
      the need for a spacer.

PMID- 14966822
TI  - Repeatability of sodium and chloride in exhaled breath condensates.
AB  - Exhaled breath condensate (EBC) has been proposed as a noninvasive tool to study
      airway inflammation. The reproducibility of breath condensates was recently
      questioned. We therefore measured sodium and chloride concentrations in EBC and
      assessed the repeatability of these measurements in healthy adults and children
      with airway disease. We investigated technical repeatability and within-day
      repeatability in five healthy adults, and compared these results with those of 10
      asthmatic children and 9 children with cystic fibrosis (CF). We also assessed
      within-period repeatability in the healthy controls. We report that the
      variability of measurements was similar for within sample, within day, and
      between visits, for both normals and children with asthma and CF, and that the
      major source of variability of sodium and chloride measurements is restricted by
      the reproducibility of the measurement assay method used. The wide use of EBC is
      more likely to depend on the development of highly sensitive and reproducible
      assays, rather than further refinements of the collection technique.

PMID- 14966823
TI  - Late presentation of congenital cystic adenomatoid malformation of lung in ten
      year-old girl.
AB  - Congenital cystic adenomatoid malformation of the lung (CCAML) is uncommon, and
      usually presents in children with respiratory distress. We describe a girl
      presenting with pneumonia at age 10 years. She had been previously healthy and
      active, and with no previous hospitalizations or X-rays. A chest CT scan showed
      right lower lobe cystic lesions suggestive of CCAML.

PMID- 14966824
TI  - Aortic hiatus gastric hernia.
AB  - Congenital diaphragmatic hernias are a relatively common anomaly that can present
      with significant respiratory morbidity and mortality. We report on a case of an
      aortic-hiatal gastric hernia that initially presented with repeated episodes of
      respiratory distress, which was diagnosed as asthma. The diagnosis of a
      diaphragmatic hernia was made at 18 months of age. In the operating room, it was
      noted that it was an aortic hiatal hernia, which was surgically repaired.
      Subsequently, there has been improvement in daily respiratory symptoms.

PMID- 14966825
TI  - Limb sparing surgery for pediatric musculoskeletal tumors.
AB  - There has been an unprecedented improvement in the survival outcome of children
      with extremity sarcoma as well as a corresponding increase in percentage of limb
      sparing surgeries being performed over the past many decades. This has been, in
      part, due to the improved imaging modalities, newer surgical techniques, and
      advences in neoadjuvant chemotherapy. Limb-sparing surgery for primary bone and
      soft-tissue malignancies in children is becoming an acceptable option of surgical
      treatment in most cases today. This article outlines the demographics,
      classification, clinical presentation, imaging, and molecular genetics of
      pediatric mosculoskeletal tumors and discusses the current treatment principles
      with emphasis on the state-of-the-art surgical management and limb-sparing
      techniques for children with extremity sarcoma.

PMID- 14966826
TI  - Outcome of patients with stage III or inoperable WT treated on the second United
      Kingdom WT protocol (UKWT2); a United Kingdom Children's Cancer Study Group
      (UKCCSG) study.
AB  - BACKGROUND: The aims of UKWT2 included consolidating the results for stage III
      patients obtained in UKWT1 and improving the outcome for patients with inoperable
      tumours by giving vincristine, actinomycin-D and doxorubicin in an intensive
      schedule (Intensive AVA). PROCEDURE: The second UK WT trial (UKWT2) ran between
      July 1986 and September 1991 accruing 448 patients. One hundred and six patients
      were diagnosed and treated for stage III disease. Six had clear cell sarcoma of
      the kidney (CCSK) and seven had rhabdoid tumours of the kidney (RTK) and are
      analysed separately. One other patient was excluded from overall analysis. Ninety
      two patients were followed for a median of 115 months. Seventy-five received
      standard chemotherapy and abdominal radiotherapy according to protocol. Seventeen
      had stage III disease at immediate nephrectomy, but radiotherapy was omitted by
      physician choice. Thirty-three patients had inoperable disease at diagnosis and
      received pre-nephrectomy chemotherapy. RESULTS: Overall survival (OS) at 4 years
      for stage III favourable histology (FH) patients receiving abdominal RT was 83%
      (CI: 73-89). For children with stage III disease in whom RT was omitted the OS
      was 82% (CI: 59-97) and for inoperable disease 94% (CI: 78-98). The overall and
      event-free survival (EFS) of children with stage III CCSK was 100% and was
      achieved with the majority of patients not receiving radiotherapy (CI: 48-100).
      Three of seven children with RTK are alive EFS and OS 43% (CI: 10-73). For
      patients treated by abdominal radiotherapy the overall local control rate was
      94.4% (CI: 86.4-98.5*%), 96.7% (CI: 88.5-99.6%) for flank RT and 83.3% (51.6
      98.0%) for whole abdominal radiotherapy (WRT). CONCLUSIONS: The outcome for stage
      III FH disease was similar to that reported for UKWT1 and NWTS-3. The combination
      of abdominal RT together with 3-drug chemotherapy achieves a high abdominal
      tumour control rate. Flank RT is probably sufficient for localised tumour
      rupture. The high cure rates for children in this trial with 'inoperable disease'
      suggests that treatment should be modified according to their post-chemotherapy
      stage in order to avoid over-treatment. The high OS for stage III CCSK on this
      protocol suggests that treatment duration could be curtailed and the role of RT
      reviewed, though the numbers are small. The prognosis for older children with RTK
      seems to be better than for younger children although larger studies are required
      to confirm this.

PMID- 14966827
TI  - Oral etoposide for recurrent/progressive sarcomas of childhood.
AB  - BACKGROUND: Etoposide (VP-16) is a topoisomerase II inhibitor that is effective
      in a broad spectrum of pediatric and adult malignancies. Chronic, low-dose, oral
      VP-16 has also been shown to be active in some recurrent malignancies mostly in
      adults. The aim of this prospective, single institution study is to assess the
      efficacy and toxicity of oral VP-16 in children with progressive or recurrent
      (P/R) sarcomas. PROCEDURE: Twenty-one children (10 girls and 11 boys) with R/P
      sarcomas and a median age of 11 years (range 3-16 years) were enrolled in this
      study. The diagnosis was Ewing sarcoma family tumor (ESFT) in seven, osteosarcoma
      in eight, rhabdomyosarcoma in four, clear cell sarcoma of soft tissue in one,
      fibrosarcoma in one patient. Oral VP-16 was administered at a dose of 50
      mg/m(2)/daily for 20 days. The next course was initiated after a 10 day rest.
      Response to oral VP-16 was assessed after two courses. RESULTS: There was an
      objective response (one complete response [CR], two partial responses [PR]) in
      three patients (14%) by two courses of oral VP-16 alone. One of these patients
      with PR achieved CR by the use of radiotherapy (RT) and further oral VP-16. Two
      more patients (9.5%) achieved CR by RT and oral VP-16. Eight (38%) patients had
      disease stabilization for 2-15 months. Two patients (9.5%) are long-term
      survivors. They are alive with no evidence of disease (NED) 79 and 94 months from
      time of relapse/progressive disease (PD). A patient developed acute myeloid
      leukemia and died. There was no major acute toxicity related to oral VP-16 in a
      total of 126 courses. CONCLUSIONS: Oral VP-16 therapy is simple, relatively
      nontoxic, and does not necessitate hospitalization. The cure rate is small. Given
      the risk of second malignancy, especially in children with previous exposure to
      topoisomerase II inhibitors and alkylating agents, this regimen may be used as a
      palliative treatment or in patients with poor prognosis.

PMID- 14966828
TI  - Factors influencing central line infections in children with acute lymphoblastic
      leukemia: results of a single institutional study.
AB  - BACKGROUND: We compared the rates of infection in external catheters (ECs) and
      totally implantable devices (TIDs) and the effect of timing of insertion in
      children with acute lymphoblastic leukemia (ALL). PROCEDURE: Central line data
      was collected on all children with ALL referred to the National Guard Hospital,
      Jeddah. Data was collected retrospectively from 1996 to September 1999 and
      prospectively thereafter. Only ECs were inserted prior to 1999 subsequently TIDs
      were preferred. RESULTS: One hundred forty eight children with ALL, mean age 5.1
      years had 129 ECs and 70 TIDs inserted for a total of 41,382 catheter days. The
      overall rate of infective episodes (infections/1,000 catheter days) was 3.43. Of
      the initial 148 lines 100 developed complications of which 76 (51%) were
      secondary to an infective episode. Only young age and treatment protocol were
      risk factors for first line infections (P < 0.05). There was weak evidence that
      ECs had an earlier time to infection compared to TIDs (P = 0.056). CONCLUSIONS:
      In this study, population central lines were associated with a high rate of
      infection. Treatment protocol and age were the only significant risk factors when
      only first lines were considered. Delaying catheter insertion for more than 3
      weeks from diagnosis did not reduce the risk of infection.

PMID- 14966829
TI  - Candida infections in children treated with conventional chemotherapy for solid
      tumors (transplant recipients excluded): The Institut Gustave Roussy Pediatrics
      Department experience.
AB  - INTRODUCTION: Advances in medical therapy have greatly improved the survival of
      children suffering from cancer. Although progress has been made in the
      eradication of malignant disease there is growing concern for the development of
      fungal infections in patients treated with chemotherapy. MATERIALS AND METHODS:
      We reviewed all episodes of pediatric candidemia that occurred between January
      1988 and December 2000. We analyzed the general characteristics of this
      population, risk factors, microbiology features, treatment, complications, and
      outcome. RESULTS: Seventeen cases of candidemia were observed during the 12 years
      of the study at an estimated incidence of 0.4%. Neutropenia occurred at the onset
      of infection in 13/17 (76.5%) children. A central venous device was present in
      all cases. Seventy-seven percent of the infections were caused by Candida
      albicans and in 85% of patients, yeasts had colonized the gastrointestinal tract.
      In 9/17 patients visceral dissemination was documented. Overall, in 77% of the
      episodes the outcome was favorable. CONCLUSIONS: Candidemia is a rare but severe
      complication in pediatric oncology. Even if the prognosis is better in children
      than in adults, Candida septicemia remains of great concern since a high
      percentage of these infections result in visceral dissemination and mortality is
      still elevated.

PMID- 14966830
TI  - Epidemiologic profile of symptomatic gastroenteritis in pediatric oncology
      patients receiving chemotherapy.
AB  - BACKGROUND: Patients with cancer who receive intensive chemotherapeutic regimens
      are subject to profound immunosuppression and are susceptible to an extended
      array of pathogens. PROCEDURE: The infectious causes of symptomatic
      gastroenteritis as evidenced by diarrhea +/- fever, vomiting, and abdominal colic
      in children following chemotherapy were prospectively monitored at National
      Cancer Institute, Cairo University. RESULTS: A total of 104 diarrhea episodes
      were recorded in our institution during a 10-month period, of which an infectious
      cause was detected in 74 (71.1%). Bacterial and fungal pathogens were isolated in
      culture from 41 (39.4%) and 24 (23.1%), respectively, while Clostridia difficile
      (C. difficile) and Cryptosporidium parvum (C. parvum) were detected in 15 (14.4%)
      and 10 (9.6%) of 104 diarrhea episodes following chemotherapy, respectively.
      Mixed infections were found in 24 of the patients; whereas, no cause was
      demonstrable in 30. Hospital acquired and mixed infections were the worst as
      regards morbidity (P = 0.004 and 0.02) and mortality (P = 0.007 and <0.001) of
      the infectious episode regardless the cause, respectively. On multivariate
      analysis, C. difficile was associated with the highest mortality rate (OR = 0.04,
      95% CI = 0.01-0.19), followed by fungal pathogens (OR = 0.20, 95% CI = 0.05-0.74)
      and bacterial infections (OR = 0.20, 95% CI = 0.05-0.79). CONCLUSIONS: Infectious
      gastroenteritis is an important cause of morbidity and mortality in hospitalized
      pediatric cancer patients receiving intensified protocols of chemotherapy.

PMID- 14966831
TI  - Acute lymphoblastic leukemia followed by a clonally-unrelated EBV-positive non
      Hodgkin lymphoma and a clonally-related myelomonocytic leukemia cutis.
AB  - BACKGROUND: Complicating malignant hematopoietic proliferations might severely
      hamper the course of acute lymphoblastic leukemia (ALL) in patients with an
      otherwise good prognosis. It is important to distinguish whether such neoplastic
      proliferations represent ALL relapses or secondary treatment-related
      malignancies. PROCEDURE: We present an 11-year-old girl with precursor-B-ALL in
      whom maintenance treatment was complicated by an isolated ALL relapse in the
      brain, nodular lymphoproliferations in the liver, and an isolated myelo-monocytic
      leukemia cutis. All these hemato-oncologic malignancies occurred in the
      background of a secondary immunodeficiency, most likely caused by cytotoxic
      treatment. RESULTS AND CONCLUSIONS: Using a stepwise molecular approach, we were
      able to demonstrate that the liver infiltrates were Epstein-Barr virus (EBV)
      positive, contained monoclonal mature B-cells with immunoglobulin heavy chain
      gene (IGH) gene rearrangements unrelated to the primary ALL, and thus represented
      a true secondary non-Hodgkin lymphoma (NHL). In contrast, the skin infiltrates
      consisted of myelo-monocytic cells with clonal IGH and T-cell receptor gamma gene
      rearrangements, identical to the precursor-B-ALL blasts at diagnosis. Thus, the
      disease course of the precursor-B-ALL patient was complicated by two different
      isolated extramedullary relapses (brain and skin) and a secondary EBV(+) B-NHL.

PMID- 14966832
TI  - Correlation of cerebrospinal fluid beta-glucuronidase activity with plasma
      methotrexate concentrations in leukemic children receiving high-dose
      methotrexate.
AB  - BACKGROUND: The activity of lysosomal enzymes is increased in body fluids during
      inflammation, in which cellular malfunction and cellular death occurs. Because
      chemotherapy also causes cell malfunction and death, for identifying a neurologic
      effect, we studied the activity of beta-glucuronidase in the cerebrospinal fluid
      (CSF) of leukemic children during treatment. PROCEDURE: The beta-glucuronidase
      activity in CSF was determined in 13 patients with B-precursor acute
      lymphoblastic leukemia (ALL) treated with the medium risk arm of ALL Berlin
      Frankfurt-Munster (BFM) 95 protocol. Plasma methotrexate (MTX) levels were
      determined at 24 and 48 hr after the infusion of high-dose (5 g/m(2)/24 hr) MTX
      (MCA phase). RESULTS: The mean (SD) beta-glucuronidase activity prior to the
      onset of chemotherapy was 19.9 (5.6) nmoles/4-methylumbelliferone/ml/hr. No
      significant changes in activity were noted during the phases of the protocol
      except of the MCA3. The activity was 24.4 (6.8) on MCA2, 28.4 (9.3) on MCA3, and
      24.1 (9.5) on MCA4. The beta-glucuronidase activity was positively correlated
      with the plasma MTX levels at both 24 hr (r = 0.483, P = 0.006) and 48 hr (r =
      0.676, P < 0.0001). No progressive changes were noted during the different phases
      of the protocol. The greatest beta-glucuronidase activity was measured in two
      patients with neurotoxicity. CONCLUSIONS: The beta-glucuronidase activity is
      increased in the CSF of leukemic children receiving high-dose MTX and
      particularly in neurotoxicity. It is positively correlated with plasma MTX
      levels. No cumulative effect of the chemotherapy was observed. The increased beta
      glucuronidase activity is most likely due to enzyme leakage through the cell
      membranes caused mainly by a toxic effect of MTX on the cells of the central
      nervous system (CNS).

PMID- 14966833
TI  - Human parvovirus B19 DNA is not detected in Guthrie cards from children who have
      developed acute lymphoblastic leukemia.
AB  - BACKGROUND: There has been much speculation about the cause of childhood acute
      lymphoblastic leukemia (ALL). It has been suggested, on the basis of findings in
      epidemiological studies, that ALL may be initiated by an in utero infection of
      the fetus. The human parvovirus B19 (B19) is etiologically related to human
      diseases, including erythema infectiosum and aplastic crisis, but it has not yet
      been considered to be involved in the development of ALL. Therefore, the aim of
      this study was to investigate, whether prenatal B19 infection could still be
      indirectly correlated with the development of childhood ALL. PROCEDURES: Fifty
      four Guthrie cards, collected at 3-5 days of age, from Swedish children who
      subsequently developed ALL, as well as from 50 healthy controls, were
      investigated by nested PCR for the presence of B19 DNA. RESULTS: B19 DNA was not
      detected in any of the Guthrie cards from ALL patients or from healthy controls,
      although all tested samples had amplifiable cellular DNA as confirmed by an HLA
      DQ specific PCR. CONCLUSION: B19 DNA was not found in any of the Guthrie cards
      from children who later developed ALL or in the healthy controls. These findings
      suggest that it is less likely that childhood ALL is associated with an in utero
      in fection with B19.

PMID- 14966834
TI  - Prevalence of and risk factors for hydrocele in survivors of Wilms tumor.
AB  - BACKGROUND: The purpose of this study is to evaluate the prevalence of hydrocele
      as a complication of Wilms tumor (WT) therapy and nephrectomy and to determine
      whether radiation therapy to the flank increases the risk. We hypothesize that
      radiation increases the risk of hydrocele formation in patients treated for WT.
      METHODS: A retrospective, medical review of the chart was completed on 57 male
      patients with WT diagnosed between 1985 and 2000. RESULTS: There is an increased
      prevalence of hydrocele in males that had a nephrectomy as part of their WT
      therapy. CONCLUSIONS: Male survivors of WT are at risk for development of a
      subsequent hydrocele that appears to be related to their prior surgery.

PMID- 14966835
TI  - Fertility of long-term male survivors of acute lymphoblastic leukemia diagnosed
      during childhood.
AB  - Fertility impairments among men treated during childhood for cancer are known to
      occur after some, but not all, types of anti-cancer therapy. This is the first
      study to evaluate proven fertility among adult male survivors of childhood acute
      lymphoblastic leukemia (ALL). In a retrospective cohort study, proven fertility
      (ever fathered a pregnancy) was evaluated by self-report among 213 men treated
      for ALL before age 18 on protocols of the Children's Cancer Group (CCG). Controls
      (N = 145) were drawn from among male siblings. Overall, with a proportional
      hazards analysis, proven fertility of male survivors was not different from that
      of controls (relative fertility (RF) = 0.95, 95% CI 0.63-1.43). However, married
      men treated before age 10 with high dose (24 cGy) cranial radiotherapy (RT),
      without spinal RT, had only 9% of the fertility of controls (Relative risk, RR =
      0.09, 95% CI 0.01-0.82). High dose cranial RT at older ages was not associated
      with a statistically significant fertility deficit (RR = 0.56, 95% CI 0.25-1.28).
      In this first study of proven fertility among men treated for childhood leukemia,
      the majority of survivors showed no evidence of fertility impairment compared to
      controls. However, men treated at a young age with high dose cranial RT may have
      impaired fertility. These results suggest that further investigation of men with
      these treatments is needed to confirm and extend these findings.

PMID- 14966836
TI  - Late effects surveillance system for sarcoma patients.
AB  - BACKGROUND: In 1998, a prospective multicenter pilot study of the 'Late Effects
      Surveillance System' (LESS) was started to investigate late effects of patients
      with Ewing, osteo- or soft-tissue sarcoma. PROCEDURE: Two hundred thirty patients
      were included in this pilot study. The patients were treated between 1/1/1998 and
      6/30/1999 according to the sarcoma protocols COSS-96, CWS-96, and EICESS-92, the
      median cumulative doses of the focussed drugs were for cisplatin: 360 mg/m(2),
      for doxorubicin: 270 mg/m(2), and for ifosfamide: 24 g/m(2). The patients were
      investigated using an organ related standardized screening methodology. We report
      on toxicities in the first year after cessation of therapy-the beginning of the
      patient follow-up-and the feasibility of LESS. RESULTS: Cardiotoxicity: 16/129
      (12%) patients treated with doxorubicin exhibited a reduced systolic heart
      function (fractional shortening (FS) <29%). Altogether three patients required
      cardiac drug therapy. Ototoxicity: In 5/73 (7%) patients treated with cisplatin a
      hearing deficit <4 kHz (>20 dB) was found. One patient needed a hearing aid.
      Nephrotoxicity: 2 of 214 (1%) patients treated with ifosfamide suffered from a
      tubulopathy, which required supplementation therapy. 10/50 (20%) showed a reduced
      fractional phosphate reabsorption. Incidence of hypomagnesemia was significantly
      increased in patients additionally treated with cisplatin. CONCLUSIONS: Some
      relevant impairments are noted in the first year after antineoplastic therapy. We
      expect to detect more major late sequelae in our prospective study during the
      increasing posttherapeutic interval. Our pilot study shows the feasibility of the
      methodology.

PMID- 14966837
TI  - Primary cardiac Burkitt lymphoma in a child.
AB  - Primary cardiac lymphoma (PCL) is a rare and usually fatal malignancy, seldom
      reported in children. This report describes the case of a 10-year-old boy who
      presented with multiple intracardiac masses which, when biopsied, proved to be
      small non-cleaved cell (Burkitt's) lymphoma. The first two cycles of chemotherapy
      according to the LMB 96 protocol were given under close cardiological
      supervision, with good response. The treatment was then continued with full-dose
      chemotherapy, without any cardiological complication. The patient who was treated
      by chemotherapy alone remains in complete remission 36 months after the end of
      treatment and can presently be considered as cured, without late cardiac effect.

PMID- 14966838
TI  - Intracranial metastasis presenting as isolated pituitary involvement in
      congenital disseminated neuroblastoma.

PMID- 14966839
TI  - Anna Morandi Manzolini (1716-1774) master sculptress of anatomic wax models.

PMID- 14966841
TI  - Re: Lanvers C et al. Pharmacology of all-trans-retinoic acid in children with
      acute promyelocytic leukemia. Med Pediatr Oncol 2003;40:293-301.

PMID- 14966842
TI  - Orthogonal time-of-flight secondary ion mass spectrometric analysis of peptides
      using large gold clusters as primary ions.
AB  - Secondary ion mass spectrometry (SIMS) for biomolecular analysis is greatly
      enhanced by the instrumental combination of orthogonal extraction time-of-flight
      mass spectrometry with massive gold cluster primary ion bombardment. Precursor
      peptide molecular ion yield enhancements of 1000, and signal-to-noise
      improvements of up to 20, were measured by comparing SIMS spectra obtained using
      Au(+) and massive Au(400) (4+) cluster primary ion bombardment of neat films of
      the neuropeptide fragment dynorphin 1-7. Remarkably low damage cross-sections
      were also measured from dynorphin 1-7 and gramicidin S during prolonged
      bombardment with 40 keV Au(400) (4+). For gramicidin S, the molecular ion yield
      increases slightly as a function of Au(400) (4+) beam fluence up to at least 2 x
      10(13) Au(400) (4+)/cm(2). This is in marked contrast to the rapid decrease
      observed when bombarding with ions such as Au(5) (+) and Au(9) (+). When
      gramicidin S is impinged with Au(5) (+), the molecular ion yield decreases by a
      factor of 10 after a fluence of only 8 x 10(12) ions/cm(2). Comparison of these
      damage cross-sections implies that minimal surface damage occurs during prolonged
      Au(400) (4+) bombardment. Several practical analytical implications are drawn
      from these observations.

PMID- 14966843
TI  - Simultaneous analytical method for the determination of TCH346 and its four
      metabolites in human plasma by liquid chromatography/tandem mass spectrometry.
AB  - TCH346 (dibenzo[b,f]oxepin-10-ylmethyl-prop-2-ynylamine) is a novel
      propargylamine compound under investigation as a putative agent in the treatment
      of chronic neurodegenerative illnesses. To support clinical studies an analytical
      method was developed for TCH346 plus its three amine metabolites and a carboxylic
      acid metabolite in human plasma. Using a two-step liquid-liquid extraction, one
      under acidic and one under basic conditions, by pH-switching both the basic and
      acidic analytes were extracted from 0.5 mL of plasma. All these basic and acidic
      compounds could be analyzed simultaneously using gradient high-performance liquid
      chromatographic (HPLC) separation with positive/negative selected reaction
      monitoring mass spectrometry. As a result of the validation study, the analytical
      method was shown to be appropriate for the determination of TCH346 and its
      metabolites CGP70861, GP42120, CGP71090, and GP54840 in plasma for forthcoming
      clinical studies. The LLOQs were set to 2, 200, 20, 20, and 200 pg/mL for TCH346,
      CGP70861, GP42120, CGP71090, and GP54840, respectively, and the ULOQ for all
      analytes was 20 000 pg/mL. All analytes were stable in 50% MeOH at 4 degrees C
      for at least one year, in human plasma stored below -70 degrees C for at least 7
      months, in human plasma below -18 degrees C for at least 6 months, in human
      plasma at room temperature for at least 1 day, and in the final extract solution
      at 4 degrees C for at least 3 days.

PMID- 14966844
TI  - Structural assignment of isomeric 2-aminopyridine-derivatized oligosaccharides
      using MSn spectral matching.
AB  - Two isomeric pairs of 2-aminopyridine (PA)-derivatized fucosylated and non
      fucosylated oligosaccharides (complex-type N-glycans of IgG) were analyzed using
      liquid chromatography/ion trap mass spectrometry (LC/ITMS) with a sonic spray
      ionization source and by varying the collision-induced dissociation voltage.
      Reproducibility of MS(n) (n = 2) spectra obtained by LC/ITMS was tested
      considering both fragment ions (m/z) and intensities. A comparison of their MS(n)
      spectra and evaluation of similarities (or matching), based on correlation
      coefficients between MS(n) spectra, was investigated as a possibility for
      structural assignment of the isomers. It is shown that such MS(n) spectral
      matching is useful and applicable to the structural assignment of relatively
      large fucosylated and sialylated PA-oligosaccharides released from IgG based on
      Bn- and Yn-type fragmentations of the corresponding [M+H+Na](2+) ions.

PMID- 14966845
TI  - New fragmentation mechanisms in matrix-assisted laser desorption/ionization time
      of-flight/time-of-flight tandem mass spectrometry of carbohydrates.
AB  - The spectra recorded by matrix-assisted laser desorption/ionization time-of
      flight/time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS/MS) of complex
      carbohydrates from human milk are presented. Besides ions originating from
      glycosidic cleavages and from sugar ring fragmentations, these spectra show
      intense peaks that may be assigned to ions produced by three new fragmentation
      pathways involving a six-atom rearrangement. These ions, together with the A
      fragments from sugar ring fragmentations, open the possibility of obtaining a
      complete mapping of the linkage positions present in the carbohydrates
      investigated by MALDI-TOF/TOF.

PMID- 14966846
TI  - An isotopic dilution approach for 1,3-butadiene tailpipe emissions and ambient
      air monitoring.
AB  - An isotopic dilution approach for 1,3-butadiene analysis in gaseous samples is
      presented. The methodology is based on active sampling on sorbent tubes and
      subsequent analysis by thermal desorption into a gas chromatography/mass
      spectrometry system. By adding a perdeuterated internal standard onto the sorbent
      tubes before sampling, and using mass spectrometric detection, the methodology
      gives high accuracy for this unstable analyte. The method has been used to
      monitor 1,3-butadiene ambient air concentrations in a residential area in
      proximity to a heavy-traffic roadway over a one-week period, for comparison with
      other traffic-related pollutants analysed by standard procedures. It has also
      been used to determine tailpipe emissions of two vehicles by standard emission
      testing procedures in a dynamometer. These vehicles were chosen as examples of
      low- and high-end emission rate vehicles, i.e., an old no-catalytic converter
      Otto engine and a new direct-injection diesel engine with catalytic converter.
      Exhaust gas emissions were 0.052 and 35.85 mg/km, reflecting differences in fuel,
      engine design, age, and presence (or not) of a catalytic abatement system. The
      ambient air results showed a weekly average concentration of 1,3-butadiene of
      0.53 microg/m(3).

PMID- 14966847
TI  - Determination of Abacavir in maternal plasma, amniotic fluid, fetal and placental
      tissues by a polarity switching liquid chromatography/tandem mass spectrometry
      method.
AB  - A rapid and efficient high-performance liquid chromatography/tandem mass
      spectrometry (HPLC/MS/MS) method for the determination of concentrations of the
      carbocyclic nucleoside antiviral Abacavir in maternal rat plasma, amniotic fluid,
      placental and fetal tissue samples has been developed and validated. All tissue
      samples were homogenized in water prior to analysis and all samples were prepared
      by acetonitrile precipitation followed by dilution with HPLC-grade water.
      Separation of the analyte and internal standard from the matrices was achieved on
      a C(8) analytical column (2.1 x 150 mm, 5 microm particle size). The mobile phase
      consisted of 10 mM ammonium acetate/acetonitrile using a gradient method at a
      flow rate of 0.25 mL/min for all matrices. The method yields retention times of
      approximately 3.4 and 5.1 min for the internal standard (Azidouridine) and
      Abacavir, respectively. For all matrices the limit of detection was approximately
      1 ng/ml. Recoveries from the different matrices ranged from 53-87% for Abacavir
      and from 69-84% for Azidouridine. Within- and between-run precision (%RSD) and
      accuracy (%Error) were under 15% for all matrices.

PMID- 14966848
TI  - Diagnostic ions for the rapid analysis by nano-electrospray ionization quadrupole
      time-of-flight mass spectrometry of O-glycans from human mucins.
AB  - Nano-electrospray ionization quadrupole time-of-flight mass spectrometry (nanoESI
      Q-TOFMS) was used for sensitive mapping and sequencing of underivatized
      oligosaccharide alditols obtained from human mucins. Using subnanomolar amounts
      of oligosaccharides previously analyzed by nuclear magnetic resonance (NMR),
      series of diagnostic ions relevant to the structural characterization of O
      glycans were deduced. Determination of the core type as well as positions and
      partial linkages of fucose residues could be readily obtained from the dominant
      [M+Na](+) ions. Differentiation of isomeric structures and glycosidic linkages
      were defined by the characteristic cross-ring (0,2)A-type cleavages in the
      negative ion mode. Tandem (MS/MS) mass spectra of [M-H](-) ions from sialylated
      or sulfated O-glycans revealed information concerning the position and linkage of
      such residues. These fragmentation rules were further applied in the structural
      determination of glycans from human colonic mucins. All these findings indicated
      the efficiency of ESI-Q-TOFMS for the determination of oligosaccharide
      composition, sequence, partial linkage and substitution, providing a wealth of
      structural information with sensitivity sufficient for the analysis of quantities
      as obtained from natural sources.

PMID- 14966849
TI  - Critical evaluation of a high-throughput analytical method for polychlorinated
      biphenyls in human serum: which detector for the establishment of the reference
      values?
AB  - A rapid screening method, previously developed and validated for the
      determination of 60 PCB congeners in human serum by using high-resolution gas
      chromatography coupled with low-resolution mass spectrometry, was applied to the
      establishment of the reference values in the general population. The reliability
      of this method was further confirmed by analyzing ten serum samples, obtained
      from the same population group involved in the original study, by electron impact
      ionization with either low- or high-resolution mass spectrometry. Analyses in
      electron capture negative ionization mode were also performed for the
      determination of 'dioxin-like' isomers. The data were found to be in good
      accordance with one another, especially for the congeners of highest
      environmental significance. Then, 162 real serum samples were analyzed for the
      presence of PCBs. Comparison with the results from other studies reported in the
      literature showed that a similar profile was observed; the most abundant
      congeners were #153, #180, #138 and #170. A statistical analysis was performed to
      determine whether there were significant correlations between PCB concentrations
      and specific variables such as age, gender, and dietary habits.

PMID- 14966850
TI  - Use of 13C to monitor soil organic matter transformations caused by a simulated
      forest fire.
AB  - Soil organic matter (SOM) transformations caused by heating were analyzed using
      the stable carbon isotope (13)C as a tracer to follow C mineralization dynamics
      and C transfers between different organic compartments. A (13)C-labelled soil,
      obtained by incorporation of (13)C-enriched Lolium perenne phytomass into a pine
      forest soil, was heated for 10 min at 385 degrees C to reproduce conditions
      typical of a forest fire and changes in total C content, potential C
      mineralization activity and C distribution between the different soil organic
      fractions were determined. Changes caused by heating on the potential soil C
      mineralization, determined by laboratory aerobic incubation, reveal alterations
      to the SOM biodegradability; some stabilized SOM showed an increase in
      biodegradability, whereas less stabilized SOM became more resistant to
      microorganisms. Chemical fractionations of SOM allowed us to monitor changes in
      its composition. As a consequence of heating, the less polymerized humic
      fractions were the most strongly affected, with the total disappearance of fulvic
      acids. A significant increase in the quantity and degree of polymerization of the
      humic acids at the expense of other more (13)C-enriched substances was also
      found. Finally, a large decrease in humin was observed, its solubilizable part
      disappearing completely, probably as a consequence of the incorporation of the
      byproducts into the free organic matter fraction.

PMID- 14966851
TI  - Liquid chromatography/time-of-flight mass spectrometric analyses for the
      elucidation of the photodegradation products of triclosan in wastewater samples.
AB  - Liquid chromatography coupled with time-of-flight mass spectrometry (LC/TOFMS)
      was applied for the identification of four new photodegradation products of
      triclosan, a major antimicrobial agent used in personal care products. Wastewater
      samples, spiked at 7 microg/mL with triclosan, were irradiated with natural
      sunlight in order to generate the photodegradation products. Aliquots of the
      spiked water samples were taken at different times of irradiation and compounds
      were isolated from the water samples by solid-phase extraction. Separation and
      detection of the compounds and degradation products were accomplished by
      LC/TOFMS, which provided highly selective information about elemental
      compositions. Accurate mass measurements for the four degradation products
      permitted postulation of proposed empirical formulae in this study. Replacement
      of chlorine atoms by hydroxyl groups and chlorine losses are the major
      degradation pathways proposed. The degradation products were formed also under
      environmental conditions in wastewater matrices, thus suggesting their presence
      in real wastewater treatment processes.

PMID- 14966852
TI  - Mass spectral fingerprints of detergents in gasolines using electrospray
      ionization.
AB  - Mass spectral fingerprints of detergents in Austrian, Hungarian, Uruguayan, and
      Chilean gasolines have been obtained using electrospray ionization mass
      spectrometry. Polymers or copolymers were observed based on ether motifs (inter
      peak spacings of 44, 58 and 72 u) in all samples. Austrian gasoline was found to
      also contain polymers based on isobutene-amine.

PMID- 14966853
TI  - Determination of (R)- and (S)-phenprocoumon in human plasma by enantioselective
      liquid chromatography/electrospray ionisation tandem mass spectrometry.
AB  - Phenprocoumon is a commonly used oral anticoagulant of the coumarin type, and has
      found extensive clinical use in the treatment of thrombophlebitis, pulmonary
      embolism and atrial fibrillation. In the course of a clinical study to
      investigate the influence of genetic polymorphisms of the CYP2C9 enzyme on
      phenprocoumon metabolism, we developed a new enantioselective liquid
      chromatography/electrospray ionisation tandem mass spectrometry (LC/MS/MS) method
      to quantify (R)- and (S)-phenprocoumon in human plasma. HPLC separation of the
      enantiomers was achieved on a Chira-Grom-2 column under isocratic conditions
      using a water/acetonitrile/formic acid eluent. For detection and quantification a
      triple-quadrupole MS system was used in the selected reaction monitoring (SRM)
      mode. As an internal standard the structurally homologous compound warfarin was
      chosen. The detector response was linear with a correlation coefficient of 0.988
      0.999 for (R)-phenprocoumon and 0.989-0.999 for (S)-phenprocoumon in the
      investigated concentration range between 62.5 and 1000 ng/mL (per enantiomer).
      The limit of detection (LOD) was 12.5 ng/mL.

PMID- 14966854
TI  - Analysis of uranium and isotopic ratio measurement in fish and marine
      invertebrates from the North Adriatic Sea by inductively coupled plasma mass
      spectrometry.
AB  - Uranium analysis in fish, echinoderms and shellfish samples collected in the
      north part of the Adriatic Sea is presented. The aim of the work was to evaluate
      uranium concentrations in samples of this kind, and also to investigate possible
      contamination from depleted uranium (DU) in consequence of the war operations
      previously conducted in that area. DU contamination was checked by measuring the
      (235)U/(238)U isotope ratio. The samples were dissolved according to the EPA 3052
      procedure, and the determinations were performed by inductively coupled plasma
      mass spectrometry (ICP-MS), optimized in order to perform isotope ratio
      measurements with good precision. The method was validated by evaluating the
      recovery from spiked samples; results in the range 93-107% were obtained. The
      isotope ratio measurement was evaluated in terms of accuracy and precision by
      analyzing the certified reference materials IAEA 326 and GBW 07305, and good
      agreement with the certified values was obtained here also. The concentration of
      uranium was higher in invertebrate samples than in fish (0.3-2 microg/g of U vs.
      0.05-0.1 microg/g, respectively). The isotope ratio measurements for all the
      samples gave values very similar to the natural ratio, permitting exclusion of
      the presence of DU.

PMID- 14966855
TI  - Sensitivity improvement of amino acids by N-terminal
      diisopropyloxyphosphorylation in electrospray ionization mass spectrometry.
AB  - With the introduction of a diisopropyloxyphosphoryl (DIPP) group at the N
      terminus of amino acids, the signal response in electrospray ionization mass
      spectrometry can be enhanced by 10-100-fold in positive mode and even more in
      negative mode. An enhancement of proton affinity due to the N-terminal DIPP
      derivatization was considered to be responsible for the sensitivity improvement
      in positive mode, which was supported by kinetic method studies. Two possible
      mechanisms, i.e., an increase in gas-phase acidity due to the introduction of the
      electron-withdrawing DIPP group, and the effect of pH on the formation of anions
      of amino acids and their phosphorylated derivatives, were considered for the
      signal response enhancement in negative mode.

PMID- 14966856
TI  - In vitro metabolism of ethoxidine by human CYP1A1 and rat microsomes:
      identification of metabolites by high-performance liquid chromatography combined
      with electrospray tandem mass spectrometry and accurate mass measurements by time
      of-flight mass spectrometry.
AB  - Ethoxidine (N-methyl-12-ethoxy-2,3,8,9-tetramethoxybenzo[c]phenanthridinium
      methylsulfonate salt) is a synthetic 2-methoxy-12-ethoxy derivative of the
      natural alkaloid fagaronine. This new inhibitor of DNA-topoisomerase I is
      considered as a potential antitumor agent with higher in vitro activity than
      fagaronine. In order to further improve the efficiency of ethoxidine, its in
      vitro biotransformation by hepatic monooxygenases and the structures of its
      metabolites were investigated by high-performance liquid chromatography (HPLC)
      combined with electrospray ionization tandem mass spectrometry (ESI-MS/MS) and
      accurate mass measurement by time-of-flight mass spectrometry (TOFMS). When
      ethoxidine was incubated with BNF-treated rat liver microsomes or with cells
      expressing different recombinant human cytochrome P450, the same four ethoxidine
      metabolites (m(1)-m(4)) were detected and were formed exclusively by CYP1A1. The
      structures of these metabolites were assigned from ESI-MS/MS mass spectra and
      compared with those of ethoxidine derivatives. Accurate mass measurements of in
      source ESI-TOFMS fragment ions exhibited successive neutral losses of C(2)H(4)
      and CO for ethoxidine and its metabolites. Whereas a 15 Da loss (methyl radical)
      was observed for the metabolites m(1)-m(4) containing a quaternary ammonium
      group, a 16 Da loss (methane) was observed for ethoxidine and could have resulted
      from the presence of two methoxy groups at adjacent positions (C-2 and C-3). The
      proposed oxidative modifications of ethoxidine were further confirmed by
      determination of the number of exchangeable hydrogen atoms and by the proposed
      elemental compositions of the metabolites based on accurate mass measurements by
      TOFMS. Two major metabolites resulted from O-demethylation of ethoxidine; one was
      tentatively identified as 12-ethoxyfagaronine (m(3)) and the second as an O
      demethylated ethoxidine isomer (m(4)). Two polar metabolites were shown to be O
      demethylated (m(1)) and hydroxylated (m(2)) derivatives of 12-ethoxyfagaronine.
      When 12-ethoxyfagaronine was incubated under the same conditions as ethoxidine,
      m(2) was formed, thus supporting the proposal that 12-ethoxyfagaronine is the
      primary oxidative product of ethoxidine.

PMID- 14966857
TI  - Surface field activated fragmentation of arginine oligomers.
AB  - Protonated arginine oligomers produced by matrix-assisted laser
      desorption/ionization (MALDI) graze at a kinetic energy of 350 eV along a surface
      of fluorinated hydrocarbon or mineral oil. The cation fragments activated by
      excitation processes during the slide on the surface are analyzed by time-of
      flight mass spectrometry. The resulting fragment ion mass spectra are interpreted
      by applying a theoretical concept of excimol accumulation and trap bond
      dissociation, suggested earlier. According to this theory, energy is accumulated
      and fragments are formed independently by each arginine residue of a sliding
      oligomer ion. It is concluded that the observed variation in the fragment ion
      spectra of the oligomers is a consequence of different oligomer velocities and
      not a fingerprint of different ion structures.

PMID- 14966858
TI  - Quantitation of human glutathione S-transferases in complex matrices by liquid
      chromatography/tandem mass spectrometry with signature peptides.
AB  - Direct quantitation of glutathione S-transferase (GST) isoforms [alpha (GST-A)
      and micro (GST-M)] in human liver cytosol was achieved by liquid
      chromatography/tandem mass spectrometry (LC/ESI-MS/MS) analysis of signature
      peptides of GST-A and GST-M and their corresponding stable isotopic peptide
      internal standards via multiple reaction monitoring (MRM). The selection of
      signature peptides was performed via trypsin digestion of commercially available
      cDNA-expressed GST-A1 and GST-M1, followed by LC/ESI-MS/MS with an ion trap mass
      spectrometer and sequencing with the TurboSEQUEST application. Quantitative
      analysis of the selected signature peptides in the multi-reaction monitoring
      (MRM) mode was performed using a triple-quadruple mass spectrometer. A series of
      human cytosol samples was quantitatively analyzed for levels of GST-A and GST-M.
      The total level of GST-A and GST-M obtained from this LC/ESI-MS/MS method was
      well correlated with the total level of GST determined by the 1-chloro-2,4
      dinitrobenzene (CDNB) method.

PMID- 14966859
TI  - Product identification and adenylyl cyclase activity in chloroplasts of Nicotiana
      tabacum.
AB  - In view of the ongoing debate on plant cyclic nucleotide metabolism, especially
      the functional presence of adenylyl cyclase, a novel detection method has been
      worked out to quantify the reaction product. Using uniformly labelled (15)N-ATP
      as a substrate for adenylyl cyclase, a qualitative and quantitative liquid
      chromatography/electrospray ionisation tandem mass spectrometry (LC/ESI-MS/MS)
      method was developed to measure de novo formed (15)N-adenosine 3',5'-cyclic
      monophosphate. Adenylyl cyclase activity was observed in chloroplasts obtained
      from Nicotiana tabacum cv. Petit Havana and the kinetic parameters and influence
      of various metabolic effectors are discussed in their context.

PMID- 14966860
TI  - Comparison of analyses of urinary 8-hydroxy-2'-deoxyguanosine by isotope-dilution
      liquid chromatography with electrospray tandem mass spectrometry and by enzyme
      linked immunosorbent assay.
AB  - A highly sensitive and selective method, using isotope-dilution liquid
      chromatography with tandem mass spectrometry (LC/MS/MS), for quantification of
      urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), an important biomarker of oxidative
      stress, was developed and compared with a method using an enzyme-linked
      immunosorbent assay (ELISA). The synthesis of (15)N(5)-8-OHdG is described. In
      this study, 140 urine samples were collected from workers in a coke oven plant,
      including samples from 49 control workers and 91 workers who had been
      occupationally exposed to polyaromatic hydrocarbons (PAHs). The major urinary
      metabolite of PAHs, 1-hydroxypyrene (1-OHP), was measured for the exposed
      workers. Results from the present study showed a significant correlation between
      these two measurements for determination of 8-OHdG (p < 0.05, r(2) = 0.70).
      However, only the LC/MS/MS measurements of urinary levels of 8-OHdG showed a
      significant difference between the exposed and the control subjects (p < 0.05).
      The ELISA method failed to demonstrate this difference. Furthermore, only by
      using the LC/MS/MS method was a significant correlation observed between the
      urinary levels of 1-OHP and 8-OHdG. These findings suggest that a highly specific
      and sensitive analytical method such as isotope-dilution LC/MS/MS is extremely
      important and necessary for accurate measurement and a comprehensive study of
      oxidative stress in human subjects.

PMID- 14966861
TI  - A fully automated method for accurate mass determination using high-performance
      liquid chromatography with a quadrupole/orthogonal acceleration time-of-flight
      mass spectrometer.
AB  - A generic LC/ESI(+)-oaTOFMS method has been developed for routine automated high
      accuracy mass determinations of different classes of substances. The system makes
      use of micro-high-performance liquid chromatography and a hybrid
      quadrupole/orthogonal acceleration time-of-flight (Q-oaTOF) mass spectrometer.
      Reproducible and accurate mass measurements were obtained using an electrospray
      dual sprayer with reserpine as reference compound, introduced into the mass
      spectrometer alternating with the samples. Experiments were performed to optimize
      analyte/reference response ratio, statistical algorithm correction setting, and
      analyte concentration. In these experiments, a clear dependence of the mass
      measurement error on the analyte/reference response ratio was observed. The
      dependence of average mass error versus different dead time correction algorithm
      settings (Np factors) was also explored. In the final automated procedure,
      verified for a statistically significant set of compounds ( approximately 550)
      obtained from a medicinal chemistry department, about 70% of the analyzed samples
      satisfied the acceptance criteria fixed at a maximum error of +/-5 ppm (mass
      range 150-800 Da).

PMID- 14966862
TI  - Mass Spectrometry of Synthetic-Polymer Mixtures Workshop, Held at the National
      Institute of Standards and Technology, Gaithersburg, Maryland, USA, 13-14
      November 2003.

PMID- 14966863
TI  - Expression of a member of tumor necrosis factor receptor superfamily, TROY, in
      the developing olfactory system.
AB  - TROY is a recently identified member of the tumor necrosis factor (TNF) receptor
      superfamily. We have previously reported that TROY induces the activation of
      nuclear factor kappaB via TNF receptor-associated factor 2, 5, and 6, and is
      strongly expressed in the developing central nervous system, including the
      olfactory bulb. In this study, we investigated the detailed cellular
      characterization of TROY-expressing cells in the developing olfactory system of
      mice using in situ hybridization and immunohistochemistry. Both mRNA and protein
      of TROY were first detected in the olfactory nerve layer (ONL) of the olfactory
      bulb at embryonic day 13.5. During late embryogenesis, TROY expression was most
      intense in the inner ONL (ONL-i). In the postnatal olfactory bulb, TROY
      expressing cells were also detected in the glomerular layer (GL), in addition to
      the ONL-i. The double-immunofluorescence method demonstrated that TROY was
      expressed in olfactory ensheathing cells (OECs) of the ONL-i, which were positive
      for neuropeptide Y (NPY), but neither S-100 nor p75 low-affinity nerve growth
      factor receptor. Some TROY-expressing cells in the ONL-i were observed with the
      astrocyte-like phenotype (GFAP+/NPY-). In addition, TROY was also detected in
      GFAP+ glial cells of the GL. Thus, TROY was expressed in some specific subsets of
      glial cells in the olfactory bulb, including OECs, suggesting that TROY may play
      some roles in the developing and adult olfactory system.

PMID- 14966864
TI  - Focal astrocyte loss is followed by microvascular damage, with subsequent repair
      of the blood-brain barrier in the apparent absence of direct astrocytic contact.
AB  - Blood-brain barrier (BBB) breakdown is a feature of cerebral ischaemia, multiple
      sclerosis, and other neurodegenerative diseases, yet the relationship between
      astrocytes and the BBB integrity remains unclear. We present a simple in vivo
      model in which primary astrocyte loss is followed by microvascular damage, using
      the metabolic toxin 3-chloropropanediol (S-alpha-chlorohydrin). This model is
      uncomplicated by trauma, ischaemia, or primary immune involvement, permitting the
      study of the role of astrocytes in vascular endothelium integrity, maintenance of
      the BBB, and neuronal function. Male Fisher F344 rats given 3-chloropropanediol
      show astrocytic damage and death at 4-24 h in symmetrical brainstem and midbrain
      nuclear lesions, while neurons show morphological changes at 24-48 h. Fluorescent
      10 kDa dextran tracers show the BBB leaking from 24 h, progressing to petechial
      haemorrhage after 48-72 h, with apparent repair after 6 days. BBB breakdown, but
      not the earlier astrocytic death, is accompanied by a delayed increase in blood
      flow in the inferior colliculus. An ED1 inflammatory response develops well after
      astrocyte loss, suggesting that inflammation may not be a factor in starting BBB
      breakdown. This model demonstrates that the BBB can self-repair despite the
      apparent absence of direct astrocytic-endothelial contact. The temporal
      separation of pathological events allows pharmacological intervention, and the
      mild reversible ataxia permits long-term survival studies of repair mechanisms.

PMID- 14966865
TI  - Electrophysiological properties of retinal Muller glial cells from myelin mutant
      rat.
AB  - The structural and functional similarities between Muller cells and
      oligodendrocytes prompted the present study of the electrophysiological
      properties of Muller (glia) cells obtained from the retinae of control and myelin
      mutant taiep rats during the postnatal developmental period (P12-P180). The whole
      cell configuration of the patch-clamp technique was used to characterize the
      general properties and the K+ currents from dissociated Muller cells. During the
      first 3 weeks of life, a decrease of the membrane resistance and an increase of
      the membrane potential were observed in Muller cells from both control and taiep
      rats. However, Muller cells from taiep rats never achieved the very negative
      membrane potential (-50 mV vs -80 mV) and the low membrane resistance
      characteristic for control cells. Furthermore, Muller cells displayed increased
      inward and outward K+ currents during postnatal development up to P30/60 in
      controls; however, in taiep rats, this increase ceased at P20/30, and low
      amplitude currents persisted into adulthood. These results provide first evidence
      of physiological changes in retinal Muller cells as a consequence of a myelin
      mutation causing a progressive deterioration of the central nervous system (CNS)
      due to a disturbance of the microtubule network of oligodendrocytes. We
      hypothesize that the progressive dysmyelination process of the optic nerve,
      accompanied by functional deficits of retinal neurons (e.g., ganglion cells),
      induces physiological alterations of Muller cells.

PMID- 14966866
TI  - Divergent consequences arise from metallothionein overexpression in astrocytes:
      zinc buffering and oxidant-induced zinc release.
AB  - Excessive accumulation of the heavy metal zinc is cytotoxic. As a consequence,
      cellular vulnerability to zinc-induced injury may be regulated by the abundance
      of proteins that maintain intracellular free zinc concentrations ([Zn2+]i). In
      this study, we overexpressed the zinc-binding protein metallothionein-II (MT) in
      astrocytes to assess its impact as (1) an acute zinc buffering mechanism, and (2)
      an oxidant-releasable zinc pool. Overexpression of MT in primary astrocyte
      cultures was accomplished using an adenoviral vector. Using the zinc-sensitive
      fluorescent indicator mag-fura-2, we monitored [Zn2+]i after stimulating zinc
      influx or oxidant treatment. With MT overexpression, we observed an acute
      buffering effect manifested as a dampening of stimulus-induced increases in
      [Zn2+]i. In contrast, we also saw enhanced zinc release with application of the
      sulfhydryl oxidizing agent 2,2'-dithiodipyridine. These results indicate that
      overexpression of a zinc-binding protein can quickly diminish [Zn2+]i following
      zinc influx, but elevate [Zn2+]i under conditions of oxidative stress, providing
      protective yet potentially endangering effects.

PMID- 14966867
TI  - Electrophysiological and molecular evidence of L-(Cav1), N- (Cav2.2), and R-
      (Cav2.3) type Ca2+ channels in rat cortical astrocytes.
AB  - Changes in intracellular Ca2+ levels are an important signal underlying neuron
      glia cross-talk, but little is known about the possible role of voltage-gated
      Ca2+ channels (VGCCs) in controlling glial cell Ca2+ influx. We investigated the
      pharmacological and biophysical features of VGCCs in cultured rat cortical
      astrocytes. In whole-cell patch-clamp experiments, L-channel blockade (5 microM
      nifedipine) reduced Ba2+ current amplitude by 28% of controls, and further
      decrease (32%) was produced by N-channel blockade (3 microM omega-conotoxin
      GVIA). No significant additional changes were observed after P/Q channel blockade
      (3 microM omega-conotoxin-MVIIC). Residual current (36% of controls) amounted to
      roughly the same percentage (34%) that was abolished by R-channel blockade (100
      nM SNX-482). Electrophysiological evidence of L-, N-, and R-channels was
      associated with RT-PCR detection of mRNA transcripts for VGCC subunits alpha1C (L
      type), alpha1B (N-type), and alpha1E (R-type). In cell-attached recordings,
      single-channel properties (L-currents: amplitude, -1.21 +/- 0.02 pA at 10 mV;
      slope conductance, 22.0 +/- 1.1 pS; mean open time, 5.95 +/- 0.24 ms; N-currents:
      amplitude, -1.09 +/- 0.02 pA at 10 mV; slope conductance, 18.0 +/- 1.1 pS; mean
      open time, 1.14 +/- 0.02 ms; R-currents: amplitude, -0.81 +/- 0.01 pA at 20 mV;
      slope conductance, 10.5 +/- 0.3 pS; mean open time, 0.88 +/- 0.02 ms) resembled
      those of corresponding VGCCs in neurons. These novel findings indicate that VGCC
      expression by cortical astrocytes may be more varied than previously thought,
      suggesting that these channels may indeed play substantial roles in the
      regulation of astrocyte Ca2+ influx, which influences neuron-glia cross-talk and
      numerous other calcium-mediated glial-cell functions.

PMID- 14966868
TI  - Responses and signaling pathways in human optic nerve head astrocytes exposed to
      hydrostatic pressure in vitro.
AB  - In this study, we examined the effects of mechanical stress induced by elevated
      hydrostatic pressure (HP) on the migration of human optic nerve head (ONH)
      astrocytes, using an in vitro model that follows repopulation of a cell-free area
      (CFA) created on a monolayer of cultured astrocytes. alpha-Tubulin staining
      detected phenotypic changes in astrocytes exposed to HP. The influence of
      proliferation in closure of the CFA was determined by incorporation of BrdU under
      1.5-cm H2O, control pressure (CP), and 10-cm H2O HP with or without 5
      fluorouracil. Under control and experimental conditions, closure of the CFA
      occurred mostly by migration and less by proliferation. Exposure to 10-cm H2O HP
      induced faster closure of the CFA at 1, 3, and 5 days. The signaling pathways
      involved in responses to HP were determined using genistein, tyrphostin A25,
      AG1478, and AG1295, inhibitors of receptor tyrosine kinases; wortmannin and
      LY294002, inhibitors of phosphatidyl inositol 3-kinase (PI-3K); and SC58236, an
      inhibitor of inducible cyclooxygenase-2 (COX2). Genistein and tyrphostin A25
      blocked HP-induced migration at 1, 3, and 5 days, but did not affect closure of
      the CFA under CP. AG1478 and AG1295 blocked HP-induced migration and partially
      inhibit closure of the CFA under CP. LY294002 blocked HP-induced migration.
      SC58236 markedly inhibited closure of the CFA under CP by inhibiting COX2
      activity. Exposure to HP, a physical stress, induced faster closure of the CFA
      via activation of members of the epidermal growth factor receptor (EGFR) family
      and PI-3K pathways. Under CP, closure of the CFA in response to denudation, a
      form of injury, is due to activation of COX2 in ONH astrocytes.

PMID- 14966869
TI  - The 36K protein of zebrafish CNS myelin is a short-chain dehydrogenase.
AB  - Previous studies identified homologues to mammalian myelin genes expressed in the
      teleost central nervous system (CNS), including myelin basic protein (MBP),
      protein zero (P0), and a member of the proteolipid protein family, DM20. In
      addition, an uncharacterized 36-kDa (36K) protein is a major component of teleost
      myelin, but is not a major component of myelin in other species. In the present
      study, we sought to better understand myelin proteins and myelination in one
      teleost, zebrafish, by molecular characterization of the zebrafish 36K protein.
      Purified zebrafish CNS myelin was isolated and the amino acid sequences of
      peptides present in the 36-kDa band were determined by mass spectrometry. These
      sequences matched a previously uncharacterized EST in The Institute for Genome
      Research (TIGR) zebrafish database that is related to the short-chain
      dehydrogenase/reductase (SDR) protein family. In vitro expression of the
      zebrafish 36K cDNA in Neuro 2a cells resulted in a protein product that was
      recognized by a 36K polyclonal antibody. The zebrafish 36K mRNA and protein
      expression patterns were determined and correlated to other known myelin gene
      expression profiles. In addition, we determined by in situ hybridization that a
      human 36K homologue (FLJ13639) is expressed in oligodendrocytes and neurons in
      the adult human cortex. This study identified a major myelin protein in
      zebrafish, 36K, as a member of the SDR superfamily; an expression pattern similar
      to other myelin genes was demonstrated.

PMID- 14966870
TI  - Regulation of MHC class II expression in glioma cells by class II transactivator
      (CIITA).
AB  - We first classified 12 malignant glioma cell lines into three different groups
      (types 1-3) with respect to major histocompatibility complex (MHC) class II
      expression and analyzed each group based on the different expression status of
      the class II transactivator (CIITA) gene. Glioma type 1 (2 of 12) showed
      constitutive expression of all class II molecules that might be mediated by
      activation of B cell-specific CIITA promoter III. Glioma type 2 represented the
      major phenotype (66.7 %) of malignant glioma cell lines, and MHC class II
      expression was induced by interferon-gamma (IFN-gamma) in this phenotype.
      Analysis of glioma tissue samples revealed that CIITA promoter IV was detected in
      9 of 11 patients (81.8%); however, promoter III was only in two (18.2%).
      Moreover, cultured glioma cells obtained from a fresh tumor sample upregulated
      expression of CIITA and class II molecules in the presence of IFN-gamma, strongly
      suggesting that glioma type 2 might be predominant in glioma tissues. Glioma type
      3 (2 of 12) showed CIITA transcripts but loss of MHC class II expression even in
      the presence of IFN-gamma. In addition, we determined that the constitutive MHC
      class II expression in the glioma cell lines (type 1) was the result of
      transcriptional activation of the CIITA gene. This phenomenon was mediated by
      global histone acetylation over 6 kb upstream from the transcriptional start site
      of CIITA promoter III. Moreover, stable transfection of CIITA promoter IV as well
      as promoter III into MHC class II inducible cell lines restored the constitutive
      expression of all class II molecules. These studies lay the foundation to
      understand the molecular basis for the expression of class II molecules in
      gliomas.

PMID- 14966871
TI  - Different uptake of cobalamin (vitamin B12) by astrocytes and oligodendrocytes
      isolated from rat spinal cord.
AB  - In the present study, we hypothesized that cobalamin (Cbl) deficiency might
      affect astrocytes and oligodendrocytes of rat spinal cord (SC) differently.
      Radiolabeled Cbl ([Cyano-14C]cyano-Cbl) was used to investigate whether the in
      vitro uptake of Cbl is different in primary cultures of oligodendrocytes and
      astrocytes. In culture medium supplemented with serum that naturally contains
      Cbl, the time course of labeled Cbl uptake by neonatal oligodendrocytes had two
      peaks, at 8 h and 24 h. No uptake was observed when the same cells were cultured
      in a serum-free medium and consequently in the absence of Cbl. Oligodendrocytes
      isolated from adult rat SC showed no uptake under any of the tested conditions.
      Astrocytes isolated from adult Cbl-deficient and newborn rat SC, both cultured in
      a medium supplemented with serum, showed peak Cbl uptake at 8 h and 12 h,
      respectively, whereas those isolated from the SC of an adult normal rat cultured
      under the same conditions showed no uptake throughout the experimental period.
      Astrocytes isolated from normal, Cbl-deficient adult rats and newborns cultured
      in a serum-free medium not containing Cbl, showed a similar trend of Cbl uptake
      with a peak at 24 h. Oligodendrocytes isolated from Cbl-deficient rats showed no
      uptake when cultured in medium with or without serum. This study provides
      evidence for a difference in the uptake of labeled Cbl between rat SC astrocytes
      and oligodendrocytes in relation to (1) age of the donor SC, (2) Cbl status of
      the donor SC, and (3) Cbl deficiency in the incubation medium that facilitates
      Cbl uptake in neonatal and adult astrocytes.

PMID- 14966875
TI  - Rational synthesis of covalently bonded organic-inorganic hybrids.
AB  - Hybrid materials based on covalently linked inorganic polyoxometalates (POMs) and
      organic species containing a delocalized pi system have drawn increasing
      attention. These hybrids, traditionally prepared by cluster assembly approaches
      that lack predictability and controllability, can now be synthesized through
      common organic reactions by using organically functionalized POM clusters as
      building blocks. This minireview highlights some of the most recent advances on a
      particular type of hybrids where the organic and inorganic components are
      connected by an imido linkage.

PMID- 14966874
TI  - Layer-by-layer deposition of polyelectrolytes--a versatile tool for the in vivo
      repair of blood vessels.

PMID- 14966876
TI  - The way into the bridge: a new bonding mode of tertiary phosphanes, arsanes, and
      stibanes.
AB  - Until recently, tertiary phosphanes, arsanes, and stibanes were considered to
      bind to transition-metal centers only in a terminal coordination mode.
      Investigations on the reactivity of square-planar trans-[RhCl(=CRR')(L)(2)]
      compounds revealed that compounds in which L=SbiPr(3) can be converted upon
      heating into dinuclear complexes [Rh(2)Cl(2)(micro-CRR')(2)(micro-SbiPr(3))] with
      the carbene and stibane ligands in bridging positions. Although attempts to
      replace the stibane in these complexes with a tertiary arsane or phosphane
      failed, substitution of the chloro ligands for acetylacetonates followed by
      bridge-ligand exchange allowed the preparation of the phosphane- and arsane
      bridged compounds [Rh(2)(acac)(2)(micro-CRR')(2)(micro-PR(3))] and
      [Rh(2)(acac)(2)(micro-CRR')(2)(micro-AsMe(3))]. The acac ligands can be replaced
      by anionic Lewis bases to give either monomeric [Rh(2)X(2)(micro-CRR')(2)(micro
      ER(3))] or dimeric chain-like [XRh(micro-CRR')(2)(micro-ER(3))Rh(micro
      X)(2)Rh(micro-CRR')(2)(micro-ER(3))RhX] molecules.

PMID- 14966877
TI  - A CuIICoII metallacyclophane-based metamagnet with a corrugated brick-wall sheet
      architecture.

PMID- 14966878
TI  - Generation of size-controlled Pd0 nanoclusters inside nanoporous domains of gel
      type resins: diverse and convergent evidence that supports a strategy of template
      controlled synthesis.

PMID- 14966879
TI  - Selective C-H bond activation by a supramolecular host-guest assembly.

PMID- 14966880
TI  - A concept for recyclable cross-linked polymers: topologically networked
      polyrotaxane capable of undergoing reversible assembly and disassembly.

PMID- 14966881
TI  - Self-assembly in gold(I) chemistry: a double-stranded polymer with interstrand
      aurophilic interactions.

PMID- 14966882
TI  - Metal-organic replica of fluorite built with an eight-connecting tetranuclear
      cadmium cluster and a tetrahedral four-connecting ligand.

PMID- 14966883
TI  - Laser-induced formation of metal-peroxide linkages on the surface of lanthanum
      sesquioxide under oxygen.

PMID- 14966885
TI  - An organic-inorganic hybrid electrolyte derived from self-assembly of a
      poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock
      copolymer.

PMID- 14966884
TI  - (C4N2H12)[FeII/(0.86)FeIII(1.14)(HPO3)1.39(HPO4)0.47(PO4)0.14F3]: a fluoro
      phosphite-hydrogenphosphate-phosphate iron(II,III) mixed-valence organically
      templated compound.

PMID- 14966886
TI  - Diorganophosphanylphosphinidenes as complexed ligands: synthesis via an anionic
      terminal phosphide of niobium.

PMID- 14966887
TI  - A 1,3-lithium shift of propargylic/allenylic lithium and the subsequent
      transmetalation coupling reaction with aryl halides.

PMID- 14966888
TI  - A unique 3D alternating ferro- and antiferromagnetic manganese azide system with
      threefold interpenetrating (10,3) nets.

PMID- 14966889
TI  - Chiral molecular recognition by aluminum tris(2,6-diphenylphenoxide) in an
      asymmetric 1,4-addition.

PMID- 14966890
TI  - C74F38: an exohedral derivative of a small-bandgap fullerene with D3 symmetry.

PMID- 14966891
TI  - Reactivity-based one-pot synthesis of oligomannoses: defining antigens recognized
      by 2G12, a broadly neutralizing anti-HIV-1 antibody.

PMID- 14966892
TI  - Denitrogenation of transportation fuels by zeolites at ambient temperature and
      pressure.

PMID- 14966893
TI  - A biomimetic pathway for hydrogen evolution from a model of the iron hydrogenase
      active site.

PMID- 14966894
TI  - Enantiodivergence in the reactions of a highly enantiomerically enriched
      silyllithium compound with benzyl halides: control of inversion and retention by
      selection of halide.

PMID- 14966895
TI  - A modular assembly of chiral oxazolinylcarbene-rhodium complexes: efficient
      phosphane-free catalysts for the asymmetric hydrosilylation of dialkyl ketones.

PMID- 14966896
TI  - Nucleophilic catalysis of the iodine-zinc exchange reaction: preparation of
      highly functionalized diaryl zinc compounds.

PMID- 14966897
TI  - Multistep binding of divalent cations to phospholipid bilayers: a molecular
      dynamics study.

PMID- 14966899
TI  - Roles of main pro- and anti-angiogenic factors in tumor angiogenesis.
AB  - Tumor growth without size restriction depends on vascular supply. The ability of
      tumor to induce new blood-vessel formation has been a major focus of cancer
      research over the past decade. It is now known that members of the vascular
      endothelial growth factor and angiopoietin families, mainly secreted by tumor
      cells, induce tumor angiogenesis, whereas other endogenous angiogenic inhibitors,
      including thrombospondin-1 and angiostatin, keep tumor in dormancy. Experimental
      and clinical evidence has suggested that the process of tumor metastasis depends
      on angiogenesis or lymphangiogenesis. This article summarizes the recent research
      progress for some basic pro- or anti-angiogenic factors in tumor angiogenesis.

PMID- 14966900
TI  - Values of mutations of K-ras oncogene at codon 12 in detection of pancreatic
      cancer: 15-year experience.
AB  - AIM: To summarize progress in the study of K-ras gene studies in pancreatic
      cancer and its potential clinical significance in screening test for early
      detection of pancreatic cancer, and to differentiate pancreatic cancer from
      chronic pancreatitis in recent decade. METHODS: Literature search (MEDLINE 1986
      2003) was performed using the key words K-ras gene, pancreatic cancer, chronic
      pancreatitis, and diagnosis. Two kind of opposite points of view on the
      significance of K-ras gene in detection early pancreatic cancer and
      differentiation pancreatic cancer from chronic pancreatitis were investigated.
      The presence of a K-ras gene mutation at codon 12 has been seen in 75-100% of
      pancreatic cancers, and is not rare in patients with chronic pancreatitis, and
      represents an increased risk of developing pancreatic cancer. However, the
      significance of the detection of this mutation in specimens obtained by needle
      aspiration from pure pancreatic juice and from stools for its utilization for the
      detection of early pancreatic cancer, and differentiation pancreatic cancer from
      chronic pancreatitis remains controversial. CONCLUSION: The value of K-ras gene
      mutation for the detection of early pancreatic cancer and differentiation
      pancreatic cancer from chronic pancreatitis remains uncertain in clinical
      practice. Nevertheless, K-ras mutation screening may increase the sensitivity of
      FNA and ERP cytology and may be useful in identifying pancreatitis patients at
      high risk for developing cancer, and as a adjunct with cytology to differentiate
      pancreatic cancer from chronic pancreatitis.

PMID- 14966901
TI  - Expression of Egr-1, c-fos and cyclin D1 in esophageal cancer and its precursors:
      An immunohistochemical and in situ hybridization study.
AB  - AIM: To examine the expression of Egr-1, c-fos and cyclin D1 at both transcript
      and protein levels in esophageal carcinoma and to correlate the level of their
      expressions with precancerous and paracancerous esophageal lesions and esophageal
      carcinoma. METHODS: In situ hybridization and immunohistochemistry were used
      respectively to detect the expression of mRNA and proteins of Egr-1, c-fos and
      cyclin D1 in 70 cases of esophageal squamous cell carcinoma and their
      corresponding para-cancerous mucosa and upper cut edge mucosa. RESULTS: In situ
      hybridization and immunohistochemistry showed positive staining of all three
      mRNAs in the cytoplasm and those of the proteins in nuclei. Overexpression of Egr
      1, c-fos and cyclin D1 mRNAs and their proteins was found in dysplasia and
      squamous carcinomas. The expression level of Egr-1 and c-fos was high, and cyclin
      D1 was low in dysplasia mucosa, whereas the expression of Egr-1 was decreased, c
      fos was maintained and cyclin D1 was increased in the cancers. The expression of
      both c-fos and cyclinD1 was consistent between the mRNA and protein in their
      corresponding high expression lesions. CONCLUSION: The expression of Egr-1, c-fos
      and cyclin D1 varies in esophageal precancerous lesions and cancer tissues,
      suggesting an involvement of these genes in the development of esophageal
      carcinoma.

PMID- 14966902
TI  - Expression of pituitary tumor transforming gene in human gastric carcinoma.
AB  - AIM: Pituitary tumor transforming gene (PTTG1) is overexpressed in a variety of
      tumors, including carcinomas of the lung, breast, colon, as well as in leukemia,
      lymphoma and pituitary adenomas. However, there is little information on its
      expression in gastric carcinoma. We sought to investigate the expression of PTTG1
      in gastric carcinoma and to explore the relationship between its expression and
      clinicopathological factors. METHODS: We studied 75 primary human gastric
      adenocarcinomas, including 17 mucosal carcinomas, 21 submucosal infiltrative
      carcinomas, 12 carcinomas invading proprial muscle layers, 6 carcinomas reaching
      the subserosa, and 19 carcinomas penetrating the serosal surface.
      Immunohistochemical analysis was performed using paraffin-embedded sections of
      gastric adenocarcinomas. RESULTS: PTTG1 was expressed heterogeneously in
      carcinomas. Positive PTTG1 staining was observed in 65.3% of the carcinomas (49
      of 75). Its expression did not correlate significantly with either the
      histological type or the depth of infiltration of the gastric carcinomas.
      However, a statistical analysis showed significant differences between the
      primary adenocarcinomas and the associated metastatic lymph nodes. CONCLUSION:
      The results of this study demonstrate that PTTG1 expression is enhanced in
      metastatic lymph nodes in comparison to that in primary carcinomas. We suggest
      that PTTG1 may contribute to lymph node metastases in gastric carcinoma.

PMID- 14966903
TI  - Anti-neoplastic efficacy of Haimiding on gastric carcinoma and its mechanisms.
AB  - AIM: To study the anti-neoplastic effect of Haimiding and its mechanisms of
      action. METHODS: Experiments using MTT and colony formation were carried out to
      study the in vitro anti-neoplastic action of Haimiding, its in vivo anti
      neoplastic action was studied by observing its effect on the weight of tumors in
      FC mice and S(180), H(22) tumor bearing mice, as well as their life spans. The
      effect of Haimiding on cell apoptosis and different stages of cell cycles in
      human gastric carcinoma cells were studied by flow cytometry. Its effect on
      [Ca(2+)](i) of human gastric carcinoma cells and the source of Ca(2+) during the
      change of [Ca(2+)](i) were observed by confocal laser scanning technique.
      RESULTS: Haimiding showed a definite cytotoxicity to 8 human tumor cell lines,
      which was most prominent against BGC-823, E(ca-109) and HCT-8 tumor cells. It
      also exhibited an obvious inhibition on colony formation of the above tumor cell
      lines, which was most prominent in E(ca-109) tumor cells. It showed obvious
      inhibition on the growth of tumor in FC mice and S(180) bearing mice as well as
      prolonged the life span of H(22) bearing mice. It was able to induce apoptosis
      and elevate intracellular [Ca(2+)](i) concentration of tumor cells. The source of
      Ca(2+) came from both extracellular Ca(2+) influx and intracellular Ca(2+)
      release. CONCLUSION: Haimiding is composed of a TCM preparation and 5
      flurouracil. Its anti-neoplastic potency is highly enhanced by synergism as
      compared with either one of its components. Its mechanisms of anti-neoplastic
      action can be attributed to its action to initiate apoptosis of tumor cells by
      opening the membrane calcium channel and inducing intracellular Ca(2+) release to
      elevate [Ca(2+)](i) of the tumor cells.

PMID- 14966904
TI  - Expression of nuclear factor-kappa B and target genes in gastric precancerous
      lesions and adenocarcinoma: association with Helicobactor pylori cagA (+)
      infection.
AB  - AIM: To examine the expression of nuclear factor kappaB (NF-kappaB) and its
      target genes in intestinal metaplasia (IM), dysplasia (DYS) and gastric carcinoma
      (GC) infected with Helicobacter pylori (H pylori) and to investigate the
      mechanism underlying H pylori cytotoxin associated gene A (cag A) infection
      leading to gastric adenocarcinoma. METHODS: Expressions of NF-kappaB/p65 and its
      target genes: c-myc, cyclinD1 and bcl-xl were immunohistochemically examined in
      289 cases of gastric biopsy and resection specimens from patients with IM, DYS
      and GC infected with H pylori. H pylori in the above mentioned tissues was
      detected by Warthin-Starry stain and rapid urease tests. IgG antibody to cagA in
      sera of the patients was measured by ELISA. RESULTS: The positive rates of NF
      kappaB/p65 were significantly higher in groups with cagA of IMI-II(28/33), IM
      III(48/52), DYSI(27/31), DYS II-III(28/32), GC(35/40) than in groups without cagA
      of IMI-II(4/17), IMIII(3/20), DYSI(3/20), DYSII-III(6/21), GC(10/23). The
      expressions of c-myc, cyclinD1, and bcl-xl were significantly higher in groups
      with cagA of IM III(47/52, 49/52, 46/52), DYSII-III(29/32, 26/32, 25/32) than in
      groups without cagA of IM III(8/20, 7/20, 5/20), DYSII-III(10/21, 8/21, 3/21),
      which were in conformity with the expression of NF-kappaB in IM III, and DYSII
      III. A significantly higher expression level of NF-kappaB/p65, c-myc, cyclinD1
      and bcl-xl was detected in intestinal type GC(27/28, 18/28, 22/28, 24/28) than in
      diffuse type GC(8/12, 3/12, 3/12, 6/12), respectively. CONCLUSION: There may be
      two different molecular mechanisms in the occurrence of intestinal and diffuse
      type gastric carcinomas. Intestinal type gastric carcinoma is strongly associated
      with high expression of c-myc, cyclinD1 and bcl-xl through NF-kappaB/p65
      activated by H pylori cagA. Inhibiting the activity of NF-kappaB is an effective
      and promising way to prevent intestinal type gastric carcinoma.

PMID- 14966905
TI  - Differential expression of genes during aflatoxin B(1)-induced
      hepatocarcinogenesis in tree shrews.
AB  - AIM: Through exploring the regulation of gene expression during
      hepatocarcinogenesis induced by aflatoxin B(1) (AFB(1)), to find out the
      responsible genes for hepatocellular carcinoma (HCC) and to further understand
      the underlying molecular mechanism. METHODS: Tree shrews (Tupaia belangeri
      chinensis) were treated with or without AFB(1) for about 90 weeks. Liver biopsies
      were performed regularly during the animal experiment. Eight shares of total RNA
      were respectively isolated from 2 HCC tissues, 2 HCC-surrounding non-cancerous
      liver tissues, 2 biopsied tissues at the early stage (30th week) of the
      experiment from the same animals as above, 1 mixed sample of three liver tissues
      biopsied at the beginning (0th week) of the experiment, and another 1 mixed
      sample of two liver tissues from the untreated control animals biopsied at the
      90th week of the experiment. The samples were then tested with the method of
      Atlas(TM) cDNA microarray assay. The levels of gene expression in these tissues
      taken at different time points during hepatocarcinogenesis were compared.
      RESULTS: The profiles of differently expressed genes were quite different in
      different ways of comparison. At the same period of hepatocarcinogenesis, the
      genes in the same function group usually had the same tendency for up- or down
      regulation. Among the checked 588 genes that were known to be related to human
      cancer, 89 genes (15.1%) were recognized as "important genes" because they showed
      frequent changes in different ways of comparison. The differentially expressed
      genes during hepatocarcinogenesis could be classified into four categories: genes
      up-regulated in HCC tissue, genes with similar expressing levels in both HCC and
      HCC-surrounding liver tissues which were higher than that in the tissues prior to
      the development of HCC, genes down-regulated in HCC tissue, and genes up
      regulated prior to the development of HCC but down-regulated after the
      development of HCC. CONCLUSION: A considerable number of genes could change their
      expressing levels both in HCC and in HCC-surrounding non-cancerous liver tissues.
      A few modular genes were up-regulated only in HCC but not in surrounding liver
      tissues, while some apoptosis-related genes were down-regulated in HCC and up
      regulated in surrounding liver tissues. To compare gene-expressing levels among
      the liver tissues taken at different time points during hepatocarcinogenesis may
      be helpful to locate the responsible gene (s) and understand the mechanism for
      AFB(1) induced liver cancer.

PMID- 14966906
TI  - Comparison of transcatheter arterial chemoembolization, laparoscopic
      radiofrequency ablation, and conservative treatment for decompensated cirrhotic
      patients with hepatocellular carcinoma.
AB  - AIM: To compare the therapeutic effect of transcatheter arterial
      chemoembolization (TACE), laparoscopic radiofrequency ablation (LRFA), and
      conservative treatment for the therapy of decompensated liver cirrhosis patients
      with hepatocellular carcinomas (HCC). METHODS: Between October 2000 and July
      2003, one hundred patients with histologically proven primary HCC and clinical
      decompensated liver cirrhosis (Child classification B or C) were included in this
      study. Forty patients received LRFA (LRFA group), twenty received TACE (TACE
      group), and forty received conservative treatment (control group). We compared
      the survival, recurrence, and complication rates in these three groups, making
      adjustment using the tumor metastatic node staging system. RESULTS: The major
      complication rate in the TACE group (9/20) was significantly higher than that in
      the LRFA group (7/40). For patients with TMN stage II HCC, the survival rate of
      the LRFA group was better than that of the TACE and control groups (P=0.003) but
      the recurrence rates between the LRFA and TACE groups did not differ. CONCLUSION:
      The LRFA group of patients had better clinical outcomes in terms of survival and
      complication rates in comparison with the TACE group or conservative treatment in
      patients with decompensated liver cirrhosis, especially in TMN patients with
      stage II HCC. LRFA is thus an appropriate alternative treatment for poor liver
      function among patients with HCC.

PMID- 14966907
TI  - Genes encoding Pir51, Beclin 1, RbAp48 and aldolase b are up or down-regulated in
      human primary hepatocellular carcinoma.
AB  - AIM: To reveal new tumor markers and target genes from differentially expressed
      genes of primary tumor samples using cDNA microarray. METHODS: The (33 )P labeled
      cDNAs were synthesized by reverse transcription of message RNA from the liver
      cancerous tissue and adjacent non-cancerous liver tissue from the same patient
      and used to hybridize to LifeGrid 1.0 cDNA microarray blot containing 8400 known
      and unique human cDNA gene targets, and an expression profile of genes was
      produced in one paired human liver tumor tissue. After a global analysis of gene
      expression of 8400 genes, we selected some genes to confirm the differential
      expression using Northern blot and RT-PCR. RESULTS: Parallel analysis of the
      hybridized signals enabled us to get an expression profile of genes in which
      about 500 genes were differentially expressed in the paired liver tumor tissues.
      We identified 4 genes, the expression of three (Beclin 1, RbAp48 and Pir51) were
      increased and one (aldolase b) was decreased in liver tumor tissues. In addition,
      the expression of these genes in 6 hepatoma cell lines was also showed by RT-PCR
      analysis. CONCLUSION: cDNA microarray permits a high throughput identification of
      changes in gene expression. The genes encoding Beclin 1, RbAp48, Pir51 and
      aldolase b are first reported that may be related with hepatocarcinoma.

PMID- 14966908
TI  - Inhibition of DNA primase and induction of apoptosis by 3,3'-diethyl-9-methylthia
      carbocyanine iodide in hepatocellular carcinoma BEL-7402 cells.
AB  - AIM: To evaluate the effects of 3,3'-diethyl-9-methylthia-carbocyanine iodide
      (DMTCCI) on DNA primase activity and on apoptosis of human hepatocellular
      carcinoma BEL-7402 cells. METHODS: DNA primase assay was used to investigate DNA
      primase activity. MTT assay was applied to determine cell proliferation. Flow
      cytometric analysis, transmission electron microscopy, DNA fragmentation assay
      were performed to detect DMTCCI-induced apoptosis. Expression levels of p53, Bcl
      2, Bcl-xL, Bad, Bax, survivin, Caspase-3 and poly (ADP-ribose) polymerase (PARP)
      were evaluated by immunoblot analysis. Caspase-3 activity was assessed with
      ApoAlert Caspase-3 colorimetric assay kit. RESULTS: DMTCCI had inhibitory effects
      on eukaryotic DNA primase activity with IC(50) value of 162.2 nmol/L. It also
      inhibited proliferation of human hepatocellular carcinoma BEL-7402 cells with
      IC(50) value of 2.09 micromol/L. Furthermore, DMTCCI-induced BEL-7402 cell
      apoptosis was confirmed by DNA fragmentation (DNA ladders and sub-G1 formation)
      and transmission electron microscopy (apoptotic bodies formation). During the
      induction of apoptosis, expression of Bcl-2, Bcl-xL and survivin was decreased,
      and that of p53, Bad and Bax was increased. Caspase-3 was activated and poly (ADP
      ribose) polymerase (PARP) was cleaved in BEL-7402 cells treated with DMTCCI.
      CONCLUSION: The present data suggest that DMTCCI has inhibitory effects on
      eukaryotic DNA primase and can induce apoptosis of BEL-7402 cells. The modulation
      of expression of p53 and Bcl-2 family proteins, and activation of Caspase-3 might
      be involved in the induction of apoptosis.

PMID- 14966909
TI  - Genomic instability of murine hepatocellular carcinomas with low and high
      metastatic capacities.
AB  - AIM: To investigate the frequency of genomic instability in murine hepatocellular
      carcinoma (HCC) cell lines Hca/A2-P(P) and Hca/163-F(F) with low and high
      metastatic capacity, and to explore its association with the occurrence and
      metastasis of hepatocellular carcinomas. METHODS: Forty microsatellite markers
      were randomly selected to examine P and F cells for genomic instability using PCR
      simple sequence length polymorphism (PCR-SSLP) analysis. RESULTS: Allelic genes
      on the chromosomes of P cell line with thirty informative microsatellite loci
      were paralleled to those of inbred strain C(3)H mouse, while those of F cell line
      with 28 loci were paralleled to those of inbred strain C(3)H mice. The frequency
      of microsatellite alterations was 37.5% and 42.5% in P cell line and F cell line,
      respectively. There were different alterations of allelic band 9 at loci between
      P and F cells, among which, the frequency of microsatellite alterations was most
      commonly seen on chromosomes 3, 7, 11 and 16. CONCLUSION: Genomic instability in
      mouse chromosomes 3, 7, 11 and 16 may play a more important role in the
      development and progression of HCC in mice. It is suggested that these two sub
      clones derived from a same hepatic tumor in homozygous mouse present different
      genetic features.

PMID- 14966910
TI  - Expression of HIF-2alpha/EPAS1 in hepatocellular carcinoma.
AB  - AIM: To investigate the expression of hypoxia-inducible factor (HIF)
      2alpha/endothelial PAS domain protein1 (EPAS1) in hepatocellular carcinoma (HCC).
      METHODS: Expression of HIF-2alpha/EPAS1 was investigated immunohistochemically on
      paraffin-embedded sections from 97 patients with HCC. To further confirm that HIF
      2alpha/EPAS1 in HCC tissues also correlated with angiogenesis, a parallel
      immunohistchemistry study of vascular endothelial growth factor (VEGF) was
      performed on these 97 cases. RESULTS: HIF-2alpha/EPAS1 could be detected in 50 of
      97 cases (51.6%), including 19 weakly positive (19.8%), and 31 strongly positive
      (31.1%), the other 47 cases were negative (48.4%). The expression of HIF
      2alpha/EPAS1was significantly correlated with tumor size, capsule infiltration,
      portal vein invasion, and necrosis. A parallel immunohistochemical analysis of
      VEGF demonstrated its positive correlation with capsule infiltration, portal vein
      invasion, and HIF-2alpha/EPAS1 overexpression, which supported the correlation of
      HIF-2alpha/EPAS1up-regulation with tumor angiogenesis. No apparent correlation
      was observed between HIF-2alpha/EPAS1 and capsular formation, presence of
      cirrhosis, and histological grade. CONCLUSION: HIF-2alpha/EPAS1 is expressed in
      most of HCC with capsular infiltration and portal vein invasion, which indicates
      a possible role of HIF-2alpha/EPAS1 in HCC metastasis.

PMID- 14966911
TI  - Transfection efficiency of pORF lacZ plasmid lipopolyplex to hepatocytes and
      hepatoma cells.
AB  - AIM: To develop a novel non-viral gene delivery system, which has a small
      particle size and a high transfection efficiency to hepatocyte and hepatoma
      cells. METHODS: Lipid-polycation-DNA lipopolyplex (LPD) was prepared by mixing
      plasmid DNA and polylysine. The resulted polyplex was incubated for 10 min at
      room temperature, following the addition of preformed cationic liposomes. The
      morphology of LPD was observed by transmission electron microscopy. The diameter
      and surface charge of LPD were measured by photon correlation spectroscopy (PCS).
      The nuclease protection ability of LPD was evaluated by agarose gel
      electrophoresis. Estimation of the transfection efficiency was performed by
      galactosidase assay in Chang cells and SMMC-7721 cells. RESULTS: LPD had a
      regular spherical surface. The average diameter and the zeta potential of LPD
      were 132.1 nm and 26.8 mV respectively. LPD could protect plasmid DNA from
      nuclease degradation after 2 hours incubation at 37 degrees while the naked DNA
      degraded rapidly. The average transfection efficiencies were 86.2+/-8.9% and
      72.4+/-6.5% in Chang cells and SMMC-7721 cells respectively. CONCLUSION: LPD has
      a rather small particle size and a high transfection activity. LPD may be a good
      non-viral vector for application in some gene delivery.

PMID- 14966912
TI  - Inhibitory effect of antisense vascular endothelial growth factor 165 eukaryotic
      expression vector on proliferation of hepatocellular carcinoma cells.
AB  - AIM: To construct antisense VEGF(165) eukaryotic expression vector PCDNA(3)-as
      VEGF(165) and to study its expression and effect on the proliferation of
      hepatocarcinoma SMMC-7721 cells. METHODS: VEGF(165) cDNA was inserted into
      polylinker sites of eukaryotic expression vector PCDNA(3) to construct PCDNA(3)
      as-VEGF(165). Then the vector was transferred into human hepatocarcinoma cell
      strain SMMC-7721 with cation lipofectamine 2000 mediated methods to evaluate the
      expression of VEGF protein and the inhibitory effect on the proliferation of
      hepatocarcinoma SMMC-7721 cells. RESULTS: The detection indicated the presence of
      VEGF cDNA in normally cultured SMMC-7721 cells by PCR. VEGF mRNA expression was
      notably decreased in SMMC-7721 cells by RT-PCR after PCDNA(3)-as-VEGF(165)
      transfection. The expression of VEGF protein was dramatically inhibited (142.01+/
      7.95 vs 1 625.52+/-64.46 pg/ml(-1), P<0.01) 2 days after transfection, which
      correlated with the dose of PCDNA(3)-as-VEGF(165)5 gene. VEGF protein was most
      expressed in PCDNA(3) transferred SMMC-7721 cells but few in PCDNA(3)-as
      VEGF(165) transferred cells by immunohistochemical staining. The apoptotic rate
      of hepatocarcinoma SMMC-7721 cells was significantly promoted (17.98+/-0.86% vs
      4.86+/-0.27%, P<0.01) and the survival rate was notably decreased (80.99+/-3.20%
      vs 93.52+/-3.93%, P<0.05) due to antisense VEGF(165) by flow cytometry (FCM). The
      transfection of antisense VEGF(165) gene resulted in the inhibitory effect on the
      proliferation of hepatocarcinoma cells by 3-(4, 5-dimethylthiazol-2-yl)-2, 5
      diphenyltetrazolium bromide (MTT) and the death of all hepatocarcinoma cells on
      day 6 after transfection. CONCLUSION: It is confirmed that antisense VEGF(165)
      can inhibit the expression of VEGF protein, interfere with the proliferation and
      induce the apoptosis of hepatocarcinoma cells in our study. Antisense VEGF(165)
      gene therapy may play an important role in the treatment of human
      hepatocarcinoma.

PMID- 14966913
TI  - Effects of epidermal growth factor and its signal transduction inhibitors on
      apoptosis in human colorectal cancer cells.
AB  - AIM: The study investigated if EGF signaling inhibitors, EGF antibody and
      tyrphostin 51 (a tyrosine kinase inhibitor), mediated the action of EGF on
      apoptosis and the expression of EGF receptors and p21 (a cyclin-dependent kinase
      inhibitor) of human colorectal cancer cells. METHODS: Human colorectal
      adenocarcinoma cells (SW480) were incubated with 0.6 mL/L dimethyl sulfoxide
      (DMSO, the control group), 225 ng/mL (37.5 nmol/L) EGF in 0.6 mL/L DMSO, 225
      ng/mL EGF+2.5 microg/mL (17 nmol/L) EGF antibody in 0.6 mL/L DMSO, or 225 ng/mL
      EGF+215 ng/mL (0.8 micromol/L) tyrphostin 51 in 0.6 mL/L DMSO. RESULTS: After 48
      h incubation, the levels of EGF in medium significantly increased (P<0.05) in the
      EGF-treated groups. The numbers of apoptotic cells were significantly fewer
      (P<0.05) in the EGF + EGF antibody and EGF + tyrphostin 51 groups than those in
      the control and EGF groups after 12 h treatments. The expression of
      phosphorylated EGF receptors in the EGF, EGF + EGF antibody, and EGF + tyrphostin
      51 groups was 176.8%, 62.4%, and 138.1% of the control group, respectively. The
      expression of p21 protein in the EGF, EGF + EGF antibody, and EGF + tyrphostin 51
      groups was 115.7%, 4.8%, and 61.5% of the control group, respectively.
      CONCLUSION: The data suggest that EGF antibody and tyrphostin 51 can inhibit the
      action of EGF on apoptosis in human colorectal cancer cells through down
      regulation of EGF receptor and p21 expression.

PMID- 14966914
TI  - Expression of thymidine phosphorylase by macrophages in colorectal cancer
      tissues.
AB  - AIM: To detect the thymidine phosphorylase (dThdPase) expression in human
      colorectal cancer tissues and cells. METHODS: Forty specimens resected from
      patients with colorectal cancer were immunohistochemically stained by 654-1, anti
      dThdPase monoclonal antibody, PG-M1, anti-macrophage marker CD68 monoclonal
      antibody. Morphometrical analysis and positive cell counting were performed. In
      27 of 40 specimens, dThdPase activity was also assayed by HPLC. Otherwise, the
      dThdPase level was measured by ELISA in 6 colorectal cancer cell lines, LS174T,
      Clone A, Colo320, CX-1, Lovo, and MIP101, as well as in 2 macrophage-like cell
      lines, THP-1 and U937. RESULTS: dThdPase activity was significantly increased in
      cancer tissues compared with adjacent normal tissue (P<0.01). In
      immunohistochemical analysis, it was confirmed that most cells expressed dThdPase
      were the stromal cells surrounding cancer nests or along the invasive margin of
      cancer. Based on their morphometrical characteristics, we found that most of them
      were tumor-associated macrophages (TAMs). The number of dThdPase-positive stromal
      cells was significantly correlated with the number of CD68-positive macrophages
      (r=0.76, P<0.0001). By ELISA, 18.2 unit/mg and 19.3 unit/mg of dThdPase protein
      were detected in THP-1 and U937, but only little was detected in 6 colorectal
      cancer cell lines. CONCLUSION: The present data suggest that dThdPase expression
      is seldom detected in colorectal carcinoma cells. TAM is the most important
      source of dThdPase in colorectal cancer tissues.

PMID- 14966915
TI  - Correlation of N-myc downstream-regulated gene 1 overexpression with progressive
      growth of colorectal neoplasm.
AB  - AIM: To study the function of N-myc downstream-regulated gene 1 (NDRG1) in
      colorectal carcinogenesis and its correlation with tumor lymph node metastasis.
      METHODS: NDRG1 was detected at its protein level by immunohistochemistry (IHC)
      and image analysis (IA), and NDRG1 mRNA was detected by in situ hybridization
      (ISH) in formalin-fixed and paraffin-embedded sections with a total of 190
      specimens including 38 normal colorectal mucosae, 31 colorectal adenomas, 45 non
      metastatic colorectal carcinomas (CRCs), 38 metastatic primary CRC and
      subsequently regional lymph nodes respectively. At the same time, the
      correlations of NDRG1 with sex, age of patients and histological types of
      colorectal carcinomas were observed. RESULTS: NDRG1 proteins were gradually
      increased in colorectal carcinogenesis (P<0.05 or P<0.01). There was a
      significant difference in the expression of NDRG1 between non-metastatic and
      metastatic CRCs (P<0.05), and the correlation was positive (P<0.01, r(s)=0.329).
      However, there was no obvious difference in the expression of NDRG1 between the
      primary sites of CRCs and that in the metastatic sites of corresponding regional
      lymph nodes, nor was there an apparent difference in sex, age, and histological
      types. The expression of NDRG1 mRNA was generally in concordance with that of
      NDRG1 protein. CONCLUSION: NDRG1 gene may play an important role in colorectal
      carcinogenesis. In addition, NDRG1 may be a putative tumor metastasis promoter
      gene and is regarded as one of the molecular biological markers that can forecast
      early metastasis of CRCs. NDRG1 gene in the metastatic sites of regional lymph
      nodes may preserve its expression characteristics in the primary sites of CRCs to
      some extent. The expression of NDRG1 is not affected by sex, age and histological
      types. The role of NDRG1 in tumor metastatic process can be demonstrated by in
      vivo and in vitro.

PMID- 14966916
TI  - Abdominal aorta transplantation after programmed cryopreservation.
AB  - AIM: To study the morphologic and cellular immunologic changes after homologous
      transplantation of the abdominal aorta in rats after programmed cryopreservation
      (-196 degrees). METHODS: Abdominal aorta was harvested from anesthetized Spraque
      Dawley (SD) rats for cryopreservation (group B) or immediate implantation (group
      A). The survival rates and apoptotic rates of aortic endothelial cells (ECs) were
      examined. The patency rates, histology and cellular immunologic changes of the
      abdominal aorta were examined on days 1, 3, 7, 14, 30, 60 after transplantation
      respectively. RESULTS: The survival rate of ECs after programmed cryopreservation
      was 90.1+/-1.79%, about 3.4% lower than that of uncryopreservation (93.5+/
      1.96%). The apoptotic rates of ECs was increased after cryopreservation (7.15% vs
      4.86%, P<0.05). The patency rate of group B was significantly higher than that of
      group A (91.6+/-12.9% vs 62.5+/-26.2%, P<0.01). CD4/CD8 ratio, TCR alpha beta and
      CD11b/CD18 ratio of group B were significantly lower than those of group A
      (P<0.05). Revivification of the cryopreserved abdominal aorta showed normal
      adventitia and intact smooth muscle cells. CONCLUSION: Cryopreservation can
      reduce homologous abdominal aortic antigenecity. Even if without administration
      of immunosuppressive agents, it is still feasible to implement homologous artery
      grafting in rats.

PMID- 14966917
TI  - Effects of Ginkgo biloba extract on cytoprotective factors in rats with duodenal
      ulcer.
AB  - AIM: To investigate the effects of Ginkgo biloba extract on cytoprotective
      factors in rats with duodenal ulcer. METHODS: Sprague-Dawley rats were randomly
      divided into four groups: sham operation without ginkgo, sham operation with
      ginkgo, duodenal ulcer without ginkgo, and duodenal ulcer with ginkgo. Rats with
      duodenal ulcer were induced by 500 mL/L acetic acid. Rats with ginkgo were
      intravenously injected with Ginkgo biloba extract from the tail at a dose of 0.5
      mg/(kg/d) for 7 and 14 days. RESULTS: Pathological result showed that duodenal
      ulcer rats with ginkgo improved mucosal healing and inflammation compared with
      those without ginkgo after 7 d treatment. After 14 d treatment, duodenal ulcer
      rats with ginkgo significantly increased weight gain (34.0+/-4.5 g versus 24.5+/
      9.5 g, P<0.05) compared with those without ginkgo. Duodenal ulcer rats
      significantly increased cell proliferation (27.4+/-4.0 and 27.8+/-2.3 BrdU
      labeled cells in duodenal ulcer rats with and without ginkgo versus 22.4+/-3.5
      and 20.8+/-0.5 BrdU-labeled cells in sham operation rats with and without ginkgo,
      P<0.05) compared with sham operation rats. Mucosal prostaglandin E(2)
      concentration significantly increased by 129% (P<0.05) in duodenal ulcer rats
      with ginkgo compared with that in those without ginkgo. Duodenal ulcer rats
      without ginkgo significantly decreased superoxide dismutase activity in the
      duodenal mucosa and erythrocytes (19.4+/-6.7 U/mg protein versus 38.1+/-18.9 U/mg
      protein in the duodenal mucosa, and 4.87+/-1.49 U/mg protein versus 7.78+/-2.16
      U/mg protein in erythrocytes, P<0.05) compared with sham operation rats without
      ginkgo. However, duodenal ulcer rats with ginkgo significantly increased
      erythrocyte superoxide dismutase activity (8.22+/-1.92 U/mg protein versus 4.87+/
      1.49 U/mg protein, P<0.05) compared with those without ginkgo. Duodenal ulcer
      rats without ginkgo significantly increased plasma lipid peroxides (4.18+/-1.12
      micromol/mL versus 1.60+/-1.10 micromol/mL and 1.80+/-0.73 micromol/mL, P<0.05)
      compared with sham operation rats without ginkgo and duodenal ulcer rats with
      ginkgo during the experimental period. CONCLUSION: Ginkgo biloba extract can
      improve weight gain and mucosal healing in duodenal ulcer rats by the actions of
      cytoprotection and antioxidation.

PMID- 14966918
TI  - Insulin expression in livers of diabetic mice mediated by hydrodynamics-based
      administration.
AB  - AIM: Transfer and expression of insulin gene in vivo are an alternative strategy
      to improve glycemic control in type 1 diabetes. Hydrodynamics-based procedure has
      been proved to be very efficient to transfer naked DNA to mouse livers. The basal
      hepatic insulin production mediated by this rapid tail vein injection was studied
      to determine its effect on the resumption of glycemic control in type 1 diabetic
      mice. METHODS: Engineered insulin cDNA was inserted into plasmid vectors under a
      CMV promoter, and transferred into STZ induced diabetic mice by hydrodynamic
      procedure. Glucose levels, body weight of treated mice, insulin levels,
      immunohistology of the liver, and quantity of insulin mRNA in the liver were
      assayed to identify the improvement of hyperglycemic complication after plasmid
      administration. Sleeping Beauty, a transposon system, was also used to prolong
      the insulin expression in the liver. RESULTS: After plasmid administration,
      Plasma insulin was significantly increased in the diabetic mice and the livers
      were insulin-positive by immunostaining. At the same time the hyperglycemic
      complication was improved. The blood glucose levels of mice were reduced to
      normal. Glucose tolerance of the treated diabetic mice was improved. Body weight
      loss was also ameliorated. The rapid tail vein injection did not cause any fatal
      result. CONCLUSION: Our results suggested that insulin gene could be efficiently
      transferred into the livers of diabetic mice via rapid tail vein injection and it
      resulted in high level of insulin expression. The basal hepatic insulin
      production mediated by hydrodynamics-based administration improved the glycemic
      control in type 1 diabetes dramatically and ameliorated diabetic syndromes.
      Hydrodynamics-based administration offers a simple and efficient way in the study
      of gene therapy for type 1 diabetes.

PMID- 14966919
TI  - Augmented regeneration of partial liver allograft induced by nuclear factor
      kappaB decoy oligodeoxynucleotides-modified dendritic cells.
AB  - AIM: To investigate the effect of NF-kappaB decoy oligodeoxynuleotides (ODNs) -
      modified dendritic cells (DCs) on regeneration of partial liver allograft.
      METHODS: Bone marrow (BM)- derived DCs from SD rats were propagated in the
      presence of GM-CSF or GM-CSF+IL-4 to obtain immature DCs or mature DCs,
      respectively. GM-CSF-propagated DCs were treated with double-strand NF-kappaB
      decoy ODNs containing two NF-kappaB binding sites or scrambled ODNs. Allogeneic
      (SD rat to LEW rat) 50% partial liver transplantation was performed. Normal
      saline (group A), GM-CSF -propagated DCs (group B), GM-CSF+IL-4 - propagated DCs
      (group C), and GM-CSF+NF-kappaB decoy ODNs (group D) or scrambled ODNs 
      propagated DCs (group E) were injected intravenously into recipient LEW rats 7
      days prior to liver transplantation and immediately after transplantation. DNA
      synthesis (BrdU labeling) and apoptosis of hepatocytes were detected with
      immunostaining and TUNEL staining postoperative 24 h, 48 h, 72 h and 84 h,
      respectively. Liver graft-resident NK cell activity, hepatic IFN-gamma mRNA
      expression and recipient serum IFN-gamma level at the time of the maximal liver
      allograft regeneration were measured with (51)Cr release assay, semiquantitative
      RT-PCR and ELISA, respectively. RESULTS: Regeneration of liver allograft was
      markedly promoted by NF-kappaB decoy ODNs-modified immature DCs but was
      significantly suppressed by mature DCs, the DNA synthesis of hepatocytes peaked
      at postoperative 72 h in group A, group B and group E rats, whereas the DNA
      synthesis of hepatocytes peaked at postoperative 84 h in group C rats and 48 h in
      group D rats, respectively. The maximal BrdU labeling index of hepatocytes in
      group D rats was significantly higher than that in the other groups rats. NF
      kappaB decoy ODNs-modified immature DCs markedly suppressed but mature DCs
      markedly promoted apoptosis of hepatocytes, liver-resident NK cell activity,
      hepatic IFN-gamma mRNA expression and recipient serum IFN-gamma production. At
      the time of the maximal regeneration of liver allograft, the minimal apoptosis of
      hepatocytes, the minimal activity of liver-resident NK cells, the minimal hepatic
      IFN-gamma mRNA expression and serum IFN-gamma production were detected in group D
      rats. The apoptotic index of hepatocytes, the activity of liver- resident NK
      cells, the hepatic IFN-gamma mRNA expression level and the serum IFN-gamma level
      in group D rats were significantly lower than that in the other groups rats at
      the time of the maximal regeneration of liver allograft. CONCLUSION: The data
      suggest that the augmented regeneration of partial liver allograft induced by NF
      kappaB decoy ODNs-modified DCs may be attributable to the reduced apoptotic
      hepatocytes, the suppressed activity of liver-resident NK cells and the reduced
      IFN-gamma production.

PMID- 14966920
TI  - A novel method for preparation of tissue microarray.
AB  - AIM: To improve the technique of tissue microarray (tissue chip). METHODS: A new
      tissue microarraying method was invented with a common microscope installed with
      a special holing needle, a sampling needle, and a special box fixing paraffin
      blocks on the microscope slide carrier. With the movement of microscope tube and
      objective stage on vertical and cross dimensions respectively, the holing
      procedure on the recipient paraffin blocks and sampling procedure of core tissue
      biopsies taken from the donor blocks were performed with the refitted microscope
      on the same platform. The precise observation and localization of representative
      regions in the donor blocks were also performed with the microscope equipped with
      a stereoscope. RESULTS: Highly-qualified tissue chips of colorectal tumors were
      produced by a new method, which simplified the conventional microarraying
      procedure, and was more convenient and accurate than that employing the existing
      tissue microarraying instruments. CONCLUSION: Using the refitted common
      microscope to produce tissue microarray is a simple, reliable, cost-effective and
      well-applicable technique.

PMID- 14966921
TI  - Levels of v5 and v6 CD44 splice variants in serum of patients with colorectal
      cancer are not correlated with pT stage, histopathological grade of malignancy
      and clinical features.
AB  - AIM: This study was designed to compare the levels of v5 and v6 splice variants
      of CD44 evaluated using ELISA test in the serum of patients with colorectal
      cancer in different stages of progression of the disease estimated in pT stage
      according to WHO score, histopathological grade of malignancy and some
      clinicopathological features. METHODS: The serum obtained from 114 persons with
      colorectal adenocarcinomas was examined using ELISA method. pT stage and grade of
      malignancy of the tumour were examined in formalin fixed and paraffin embedded
      materials obtained during operation. RESULTS: Only the level of CD44 v5 in the
      serum of patients before operation with G2 pT4 tumour was lower than that in
      other probes and the difference was statistically significant. We did not find
      any other correlations between the level of v5 and v6 CD44 variants and other
      evaluated parameters. CONCLUSION: The level of CD44 v5 and v6 estimated by ELISA
      test in the serum can not be used as a prognostic factor in colorectal cancer.

PMID- 14966922
TI  - Does recombinant human erythropoietin accelerate correction of post-ulcer
      bleeding anaemia? A pilot study.
AB  - AIM: Anaemia caused by acute upper gastrointestinal bleeding is treated with
      blood transfusion or iron, but patients usually face a two-month recovery period
      from post-haemorrhage anaemia. This prospective, randomised, open, pilot study
      was designed to investigate whether recombinant human erythropoietin (Epoetin)
      therapy accelerate haematocrit increase in the post-bleeding recovery period.
      METHODS: We studied hospitalised patients admitted because of acute ulcer
      bleeding or haemorrhagic gastritis, who had a haematocrit of 27-33% and did not
      receive blood transfusions. One day after the endoscopic confirmation of
      cessation of bleeding, they were randomised either to erythropoietin (20 000 IU
      Epoetin alfa subcutaneously, on days 0, 4 and 6) plus iron (100 mg im, on days 1-
      6, (G(1)) or iron only (G(2)). Haematocrit was measured on days 0, 6, 14, 30, 45,
      and 60, respectively. RESULTS: One patient from G(1) and two from G(2) were lost
      to follow-up. Therefore, 14 and 13 patients from G(1) and G(2) respectively were
      analysed. Demographic characteristics, serum iron, ferritin, total iron binding
      capacity, reticulocytes, and haematocrit were not significantly different at
      entry to the study. Median reticulocyte counts were significantly different
      between groups on day six (G(1): 4.0, 3.0-6.4 vs G(2): 3.5, 2.1-4.4%, P=0.03) and
      median haematocrit on day fourteen [G(1): 35.9, 30.7-41.0 vs G(2): 32.5, 29.5
      37.0% (median, range), P=0.04]. CONCLUSION: Erythropoietin administration
      significantly accelerates correction of anemia after acute ulcer bleeding. The
      haematocrit gain is equivalent to one unit of transfused blood two weeks after
      the bleeding episode.

PMID- 14966923
TI  - Correlation of ATP7B genotype with phenotype in Chinese patients with Wilson
      disease.
AB  - AIM: To determine the mutational characterization of P-type ATP7B gene and to
      explore the correlation of ATP7B genotype to phenotype in Chinese patients with
      Wilson disease (WD). METHODS: Seventy-five patients with WD from 72 no-kinship
      families, 44 males and 31 females, were enrolled in this study. The age of onset
      ranged from 4 to 39 years, <=18 years in 72 patients. Some exons of ATP7B gene
      mutations were analyzed in patients with WD by using biochemical methods,
      polymerase chain reaction-single strand configuration polymorphism (PCR-SSCP) and
      DNA sequence analysis. A total of 778 coding regions were identified with
      restriction enzyme Msp I. The activity of Cu-ATPase was assessed by measuring
      inorganic phosphorus. RESULTS: Sixty-six of 75 patients (88%) had with hepatic
      manifestations, 39 of them had only hepatic manifestations, 27 patients had
      hepatic and neurological manifestations or other symptoms at the same time (16
      patients had associated neurological manifestation, 3 patients had osteopathy, 8
      patients had other symptoms). Eight of the 75 patients (10.7%) had only
      neurological symptoms, one patient (5 years old) had no symptom. Twelve changing
      patterns were detected in ATP7B gene by DNA sequencing, including seven mutations
      (R778L, C656X, G943D, V1140A, V1106I V1216M and 1384del17), six polymorphisms
      (IVS4-5t/c, A2495G, C2310G, IVS18+6c/t and IVS20+5a/g). R778L occurred in 49/66
      patients (74%) with hepatic manifestations, homozygosis of R778L in 16 patients,
      heterozygosity of R778L in 33 patients. V1106I mutation of ATP7B gene occurred in
      2 patients with delaying onset of clinical symptoms. Cu-ATPase activity of three
      patients with known mutations (R778L/V1106I/A2495G, R778L/V1216M and R778L/R778L)
      were determined, and the activity of Cu-ATPase was decreased by 44.55%, 88.23%
      and 69.49% respectively. CONCLUSION: 1384del17bp is a novel mutation found in WD
      patients. R778L is the most common mutation of ATP7B gene. There is a correlation
      between R778L and hepatic manifestations in WD patient.

PMID- 14966924
TI  - Effects of nitric oxide on gastric ulceration induced by nicotine and cold
      restraint stress.
AB  - AIM: Stress induces gastric ulceration in human and experimental animals. People
      tend to smoke more cigarettes when under stress. Nitric oxide (NO) and nicotine
      have opposing effects on gastric integrity. The present study examined the
      possible therapeutic benefit of NO in nicotine-treated rats with stress-induced
      gastric ulceration. METHODS: Rats drank a nicotine solution while control rats
      drank tap water for 20 days. The alkoloid was then replaced by water with or
      without supplementation of isosorbide dinitrate (NO donor) for an additional 10
      days. Isosorbide dinitrate was given twice shortly before experiments (acute) or
      three times daily by oral gavages for 10 days after the rats stopped drinking
      nicotine solution. At the end of experiments, ulcer index, gastric adhesion mucus
      content and MPO activity were measured and analysed. RESULTS: Nicotine treatment
      decreased gastric mucus content and intensified stress-induced gastric ulcer. A
      higher ulcer index persisted even after the rats stopped drinking nicotine
      solution for 10 days. Acute NO donor showed no benefit on both mucus and ulcer
      index in nicotine treatment or/and stress condition. Chronic NO donor treatment
      reversed the worsening action of nicotine in stomach. Stress increased gastric
      mucosal myeloperoxidase (MPO) activity, which was antagonized by chronic NO
      treatment. However, nicotine was unlikely to change mucosal MPO activity.
      CONCLUSION: The intensifying action of nicotine on stress-induced gastric
      ulceration persists for 10 days after cessation. Nicotine treatment significantly
      decreases gastric mucus content that can be restored by chronic NO donor
      treatment. The present study suggests that NO antagonizes the ulcerogenic action
      of nicotine through a cytoprotective way.

PMID- 14966925
TI  - Helicobacter species sequences in liver samples from patients with and without
      hepatocellular carcinoma.
AB  - AIM: Only a minority of patients carrying a defined viral aetiologic agent
      develop cirrhosis and ultimately hepatocellular carcinoma (HCC), the mechanism
      underlying the worsening is still undefined. Experimental infection by
      Helicobacter hepaticus in mice causes chronic hepatitis and HCC and recently,
      more Helicobacter species (Helicobacter spp.) have been detected in the liver of
      patients suffering from cholestatic diseases and HCC arising from non-cirrhotic
      liver. We investigated whether Helicobacter spp. sequences could be detected in
      the liver of patients with cirrhosis and HCC compared to subjects with metastasis
      to liver from colon cancer. METHODS: Twenty-three liver samples from patients
      operated upon for HCC superimposed on hepatitis C virus (HCV)-related cirrhosis
      and 6 from patients with resected metastases from colorectal cancer, were tested
      by polymerase chain reaction for presence of genomic 16S rRNA of Helicobacter
      genus using specific primers. DNA sequencing and cag A gene analysis were also
      performed. RESULTS: Genomic sequences of Helicobacter spp. were found in 17 of 20
      (85%) liver samples from patients with HCC and in 2 of 6 samples from patients
      with liver metastasis. In three samples of the first group the result was
      uncertain. H pylori was revealed in 16 out of 17 positive samples and
      Helicobacter pullorum in the other. CONCLUSION: Helicobacter spp., carcinogenic
      in mice, were found at a higher frequency in the liver of patients with HCV
      related cirrhosis and HCC than those in patients without primary liver disease.

PMID- 14966926
TI  - Genotypes of Helicobacter pylori in patients with peptic ulcer bleeding.
AB  - AIM: Helicobacter pylori causes chronic gastritis, peptic ulcer, gastric cancer
      and MALT-lymphoma. Different genotypes of Helicobacter pylori are confirmed from
      diverse geographic areas. Its association with bleeding peptic ulcer remains
      controversial. The aim of this study was to investigate the Helicobacter pylori
      vacA alleles, cagA and iceA in patients with bleeding peptic ulcer. METHODS: We
      enrolled patients with bleeding, non-bleeding peptic ulcers and chronic
      gastritis. Biopsy specimens were obtained from the antrum of the stomach for
      rapid urease test, bacterial culture and PCR assay. DNA extraction and polymerase
      chain reaction were used to detect the presence or absence of cagA and to assess
      the polymorphism of vacA and iceA. RESULTS: A total of 168 patients (60.4%) (25
      patients with chronic gastritis, 26 patients with bleeding gastric ulcer, 51
      patients with non-bleeding gastric ulcer, 26 patients with bleeding duodenal
      ulcer, and 40 patients with non-bleeding duodenal ulcer) were found to have
      positive PCR results between January 2001 and December 2002. Concerning
      genotypes, we found cagA (139/278, 50%), vacA s1a (127/278, 45.7%), and ice A1
      (125/278, 45%) predominated in all studied patients. In patients with bleeding
      peptic ulcers, vacA s1a and m1T were fewer than those in patients with non
      bleeding peptic ulcers (37/106 vs 69/135, P=0.017, and 4/106 vs 21/135, P
      =0.002). CONCLUSION: In patients with peptic ulcers, H pylori vacA s1a and m1T
      prevent bleeding complication.

PMID- 14966927
TI  - Abnormal function of platelets and role of angelica sinensis in patients with
      ulcerative colitis.
AB  - AIM: To explore the abnormal function of platelets and the role of angelica
      sinensis injection (ASI) in patients with ulcerative colitis (UC). METHODS: In 39
      patients with active UC, 25 patients with remissive UC and 30 healthy people,
      alpha-granule membrane protein (GMP-140) and thromboxane B(2) (TXB(2)) were
      detected by means of ELISA, 6-keto-PGF(1a) was detected by radioimmunoassay,
      platelet count (PC) and 1 min platelet aggregation rate (1 min PAR) were detected
      by blood automatic tester and platelet aggregation tester respectively, and von
      Willebrand factor related antigen (vWF:Ag) was detected by the means of
      monoclonal -ELISA. The 64 patients with UC were divided into two therapy groups.
      After routine treatment and angelica sinensis injection (ASI) + routine treatment
      respectively for 3 weeks, all these parameters were also detected. RESULTS: The
      PC, 1 min PAR and levels of GMP-140, TXB(2), and vWF:Ag in active UC were
      significantly higher than those in remissive UC and normal controls (P<0.05
      0.01).Meanwhile, 1 min PAR and levels of GMP-140, TXB(2), and vWF:Ag in remissive
      UC were still significantly higher than those in normal controls (P<0.05).
      Furthermore, 6-keto-PGF(1a) level in active and remissive UC was remarkably lower
      than that in normal control (P<0.05-0.01). These parameters except 6-keto-PGF(1a)
      were significantly improved after the treatment in ASI therapy group (P<0.05
      0.01), whereas they all were little changed in routine therapy group (P>0.05).
      CONCLUSION: Platelets can be significantly activated in UC, which might be
      related with vascular endothelium injury and imbalance between TXB(2) and 6-keto
      PGF(1a) in blood. ASI can significantly inhibit platelet activation, relieve
      vascular endothelial cell injury, and improve microcirculation in UC.

PMID- 14966928
TI  - Effects of lipopolysaccharides stimulated Kupffer cells on activation of rat
      hepatic stellate cells.
AB  - AIM: To study the effects of Kupffer cell-conditioned medium (KCCM) derived from
      lipopolysaccharide (LPS) treatment on proliferation of rat hepatic stellate cells
      (HSC). METHODS: HSC and Kupffer cells were isolated from the liver of Wistar rats
      by in situ perfusion with pronase and collagenase and density gradient
      centrifugation with Nycodenz and cultured. KCCM was prepared and 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay
      was used to detect HSC proliferation. The content of type IV collagen and laminin
      secreted by HSC in the HSC-conditioned medium was determined by radioimmunoassay.
      TGF-beta(1) production in the KCCM was detected by enzyme-linked immunosorbent
      assay (ELISA). RESULTS: HSC and Kupffer cells isolated had high purity. One
      microgram per mililiter LPS-activated KCCM and unstimulated KCCM could
      significantly promote HSC proliferation [0.132+/-0.005 and 0.123+/-0.008 vs
      control group (0.100+/-0.003), P<0.01], and there was a difference between them
      (P<0.05). Ten microgram per mililiter LPS-activated KCCM (0.106+/-0.010) was
      unable to promote HSC proliferation (P>0.05). Adding anti-TGF-beta(1) antibodies
      could suppress the proliferation promoted by unstimulated KCCM and LPS (1
      microg/ml)-activated KCCM (0.109+/-0.009 vs 0.123+/-0.008, 0.115+/-0.008 vs
      0.132+/-0.005, P<0.01). LPS (1 microg/ml or 10 microg/ml) could not promote HSC
      proliferation immediately (0.096+/-0.003 and 0.101+/-0.004 vs 0.100+/-0.003,
      P>0.05). There was a parallel behavior between HSC proliferation and increased
      ECM level. One microgram per mililiter LPS-activated KCCM contained a larger
      amount of TGF-beta(1) than unstimulated KCCM. CONCLUSION: The technique for
      isolation of HSC and Kupffer cells described here is simple and reliable. KCCM
      stimulated by LPS may promote HSC proliferation and collagen accumulation, which
      are associated with hepatic fibrogenesis.

PMID- 14966929
TI  - Significance of perigastric lymph node involvement in periampullary malignant
      tumor.
AB  - AIM: To determine the perigastric lymph node involvement in periampullar tumors,
      in an attempt to optimize the surgical treatment of pylorus- preserving
      pancreatoduodenectomy. METHODS: We retrospectively investigated the frequence of
      lymph nodes involvement in perigastric regions. Distribution and number of
      involved lymph nodes were examined from 112 patients with carcinoma of pancreas,
      59 patients with distal bile duct carcinoma, and 41 patients with carcinoma of
      the papilla of Vater. RESULTS: The frequency of lymphatic spread of carcinoma in
      pancreas; distal bile duct and papilla of Vater was 18.7%, 1.9%, 2.5%
      respectively. With regard to the mode of lymphatic spread in perigastric region,
      Infrapyloric nodes of carcinoma of the head of pancreas predominated over
      others,in carcinomas of the distal bile duct and the papilla of Vater, the left
      gastric artery, and the greater curvature lymph nodes was the only sole sites,
      respectively. CONCLUSION: Understanding perigastric lymphatic involvement in
      periampullary tumors may be helpful for choosing the appropriate surgical
      approaches to pancreatoduodenectomy with preservation of pylorus.

PMID- 14966930
TI  - [Advances in pharmaceutical analysis].

PMID- 14966931
TI  - [Effects of microsome enzyme induced by phenobarbarbital on the stereoselectivity
      of recemic propranolol glucuronidation metabolism].
AB  - OBJECTIVE: To study the stereoselectivity of R-(+) and S-(-)-propranolol
      glucuronidation and metabolic interaction between R(+)- and S-(-)-propranolol.
      METHODS: A RP-HPLC analytical method was developed for determination of R-(+)-and
      S-(-)-propranolol glucuronide (PG) incubated with rat hepatic microsome induced
      with phenobarbital (PB). The method was applied to investigate the
      stereoselectivity metabolism of racemic propranolol glucuronidation in vitro.
      RESULT: In control and PB group, the concentration of R-(+)-PG produced at
      different substrates was higher than that of S-(-)-PG. Compared with the control,
      the V(max) and Cl(int) for R(+)-and S-(-)-propranolol increased significantly 
      the K(m) for R(+)-propranolol was elevated, while that for S-(-) propranolol was
      decreased. CONCLUSION: There is a stereoselectivity in glucuronidation of
      propranolol in rat hepatic microsome induced with PB and R-(+)-propranolol is
      preferred. Metabolic interaction between R-(+)-and S-(-)-propranolol exists with
      a concentration-dependent mode.

PMID- 14966932
TI  - [Direct resolution of calcium folinate stereoisomers using a bovine serum albumin
      chiral HPLC column].
AB  - OBJECTIVE: To establish a direct and fast method separating calcium levofolinate
      and calcium dextrofolinate in a bovine serum albumin stationary phase chiral
      column. METHODS: Using EC150/4 RESOLVOSIL BSA-7(150 mm x 4 mm) chiral separation
      column, with 0.20 mol/L, pH=5.0 phosphate buffer as mobile phase HPLC method was
      performed to separate calcium folinate enantiomers. RESULT: The capacity factor
      and resolution of the two calcium folinate enantiomers were greatly affected by
      mobile phase buffer concentration,pH and the column temperature. And the
      retention time of calcium levofolinate and calcium dextrofolinate were 18.5 min
      and 22.6 min, respectively. The resolution, R(s)=1.49. CONCLUSION: Calcium
      folinate enantiomers are separated successfully using this method.

PMID- 14966933
TI  - [Glucuronidation and in vitro interaction of Ginkgo flavonoids with other drugs].
AB  - OBJECTIVE: To obtain the information on the glucuronidation of Ginkgo flavonoid
      and the interaction profile of Ginkgo flavones with other drugs in vitro.
      METHODS: Ginkgo flavonoids (quercetin, isorhamnetin and keampferol) and other
      drugs were co-incubated with rat hepatic microsome at 25 degree; the residual
      concentrations of flavonoids were determined by HPLC. The enzymatic parameters of
      quercetin, isorhamnetin and keampferol metabolism were assessed. The interactions
      between flavonoids and these drugs on glucuronidation were observed. RESULT: The
      K(m) values were ( 24+/-0.05), (148+/-0.09) and (110+/-0.03) micromol/L and the
      V(max) values were (60+/-0.21), (48+/-0.02) and (34+/-0.02) micromol x g(-1) x
      min(-1) for quercetin, isorhamnetin and kaempferol, respectively. The IC(50) of
      nifedipine propafenone ipriflavone and diphenytriazol on flavonoids metabolism
      were 54 - 70, 69 - 122, 85 - 98 and 210 - 362 micromol, respectively. The
      inhibition constants (Ki) of diphenytriazol propafenone and ipriflavone on
      quercetin, isorhamnetin and keampferol metabolism were (57.6, 50.5, 33.1) (33.6,
      59.5, 45.2) and(13.7,24.0,15.7) microg/ml respectively. The ratio [I]/[Ki] of the
      plasma concentration and inhibition constant for propafenone was 0.002 - 0.003.
      CONCLUSION: The metabolic level of quercetin is the strongest among three Ginkgo
      flavonoids. Nifedipine propafenone and ipriflavone inhibit the metabolism of
      quercetin, isorhamnetin and keampferol at different levels. Because of the
      interaction between Ginkgo flavonoids with nifedipine, caution must be taken when
      two drugs are used together clinically.

PMID- 14966934
TI  - [Interaction between ipriflavone and other drugs in metabolism in vitro].
AB  - OBJECTIVE: To investigate the metabolism-based interaction between
      ipriflavone(IP) and other drugs in vitro. METHODS: IP and propafenone or
      estradiol, or other drugs were co-incubated with rat liver microsome induced by
      beta-naphthoflavone. The concentrations of residual substrate in microsomal
      incubates were determined by HPLC. RESULT: The metabolism of propafenone (10
      microg/ml) incubated with 2 microg/ml or 50 microg/ml IP was markedly inhibited
      compared with control group(P<0.01). While the metabolism of 10 microg/ml of
      estradiol incubated with 10 microg/ml and 100 microg/ml IP showed no marked
      inhibition. When IP (20 microg/ml) was incubated with 0.5 microg/ml propranolol,
      0.5 microg/ml propafenone or 5.0 microg/ml estradiol respectively the metabolic
      activity of IP was markedly inhibited compared with control group (P<0.05 P<0.05
      P<0.02 respectively). CONCLUSION: The results indicate that there is an
      interaction between ipriflavone and propafenone during in vitro metabolism, and
      there might also be clinical significance.

PMID- 14966935
TI  - [HPLC fingerprint of the tablets of Ginkgo biloba L].
AB  - OBJECTIVE: To establish the method for determination of the fingerprint of
      tablets of Ginkgo biloba L. METHODS: HPLC-DAD was used to determine the
      constituents in tablets. Diamonsil C18(200 mm x 4.6 mm, 5 microm) was used as
      analysis column and acetonitrile/KH(2)PO(4) as mobile phase with gradient
      elution. The column temperature was at 24 degree. The profile of chemical
      constituents in control sample and tablets obtained from the chromatograms were
      analyzed by similarity software. RESULT: The method developed for components
      analysis of the standard extracts was linear within certain concentration
      (r>0.999). There was no difference between the fingerprints of 3 batches of
      products. The fingerprints of tablets and the extract showed a good
      similarity(>0.965). CONCLUSION: This method is accurate simple and can be used
      for the quality control of Ginkgo biloba L. preparations.

PMID- 14966936
TI  - [Determination of luteolin and luteolin-7-beta-D-glucoside in Chrysanthemum
      morfolium Ramat. from different collection time by RP-HPLC].
AB  - OBJECTIVE: To observe the content variation of luteolin and luteolin-7-beta-D
      glucoside in Chrysanthemum morifolium Ramat. (CMR) from different collection
      time. METHODS: RP-HPLC was used to analyze these two components in CMR collected
      in 2001 and 2002. RESULT: The content of luteolin was significantly lower than
      that of luteolin-7-beta-D-glucoside. Furthermore, the former showed no marked
      changes during collection, while the latter did not varied markedly in early
      collection but decreased significantly in later collection. CONCLUSION: The
      content of luteolin-7-beta-D-glucoside reflects the quality of Chrysanthemum
      morifolium Ramat. more viably than that of luteolin.

PMID- 14966937
TI  - [Determination of three formulations of pilocarpine in rabbit ocular aqueous by
      RP-HPLC].
AB  - OBJECTIVE: To develop an RP-HPLC method for assay of pilocarpine in rabbit ocular
      aqueous humor. METHODS: The RP-HPLC method was performed on a column of ODS-C(18)
      with the mobile phase consisting of 0.5% of triethylamine (TEA) of phosphate
      solutions (10 mmol/L, pH 2.5) and acetonitrile (98/2,v/v). The detection
      wavelength was 215 nm and flow rate was 1.0 ml/min. Ninety albino rabbits were
      divided into 3 groups (30 in each):group 1 received 50 microl of eye drops
      containing 1% generic pilocarpine, group 21% mixture pilocarpine solution
      consisting of aqueous sample and liposome and group 31% liposome pilocarpine,
      respectively. The aqueous humor was withdrawn at 5, 10, 30, 40, 60, 90, 120, 180,
      240 and 360 min. Pilocarpine was extracted from aqueous humor with
      dichloromethane. RESULT: The linear calibration curve was obtained in the
      concentration range of 0.1 - 20 microg/ml. The average recovery was (68.1+/-2.7)%
      (n=9). Inter-day and intra-day RSD were 4.33% and 2.87%, respectively. In three
      formations 1% liposome pilocarpine was the best for the areas under curve and
      measurable amounts. CONCLUSION: The RP-HPLC method is simple and reliable for
      pilocarpine measurement in ocular aqueous. Liposome formulation can significantly
      increase the bioavailability of pilocarpine in ocular aqueous.

PMID- 14966938
TI  - [HPLC determination of zolmitriptan and its related substances].
AB  - OBJECTIVE: To develop an analytical method and quality control for determination
      of zolmitriptan and related substances. METHODS: Zolmitriptan and related
      substances were separated and determined on a shimadzu CLC-C(8) column (150 mm x
      6 mm, 10 microm) with a mobile phase of acetonitrile-10 mmol/L phosphate buffer
      (25:75 pH 7.5) and a flow-rate of 1 ml/min; the UV-VIS detector was operated at
      229 nm. RESULT: The limit of detection for the related substances was 0.5 ng on
      the zolmitriptan basis (S/N >3). Linear calibration curve was gene rated from 4 -
      40 microg/ml with a correlation coefficient of 0.9999. The recovery rate of
      zolmitriptan was 99.1% with a standard deviation of 0.2%. The results of HPLC
      method were consistent with those of nonaqueous titration method. CONCLUSION:
      HPLC method is a rapid sensitive and accurate method for the determination of
      zolmitriptan and its related substances.

PMID- 14966939
TI  - [Cloning and expression of Porphyromonas gingivalis pgmA gene encoding outer
      membrane protein associated with fimbria].
AB  - OBJECTIVE: To clone pgmA gene of Porphyromonas gingivalis, to construct the
      expression vector of the gene and to identify immunity of the fusion protein.
      METHODS: The pgmA genes from ATCC 33277 and 47A-1 strains of P.gingivalis were
      amplified by high fidelity PCR. The nucleotide of the target DNA amplification
      fragments were sequenced after T-A cloning. The pET32a expression vectors
      inserted with pgmA gene fragments were constructed. PgmA fusion protein was
      expressed in E.coli strain BL21DE3 induced by IPTG with different dosages.
      Western blot test by using rabbit antiserum against the fusion protein was
      applied to determine immunity of the fusion protein. ELISA was applied to
      determine the immunoreaction of antibody against PgmA fusion protein and 65
      strains of P.gingivalis isolates. RESULT: The nucleotide sequence homology of the
      cloned pgmA gene fragments from ATCC 33277 and 47A-1 strains was 100%. In
      comparison with the reported corresponding sequences, the homologies of the
      nucleotide sequences of the cloned pgmA gene fragments were 98.98%, while the
      homologies of their putative amino acid sequences were 99.18%. The expression
      output of PgmA fusion protein in pET32a-pgmA-BL21DE3 system was approximately 50%
      of the total bacterial proteins. PgmA fusion protein was able to induce rabbit to
      produce specific antibody that could combine with PgmA protein. 92.3% of P.
      gingivalis isolates (60/65) were able to react with the antibody against PgmA
      fusion protein. CONCLUSION: An expression system of P.gingivalis pgmA gene with
      high efficiency was established successfully. The expressed PgmA fusion protein
      possesse satisfied immunogenicity and immunoreactivity,which can be used as a
      candidate antigen in detection of P.gingivalis and possible development of
      corresponding vaccine.

PMID- 14966940
TI  - [Expression of transforming growth factor-beta1 in renal fibrosis of human
      mesengial proliferative glomerulonephritis].
AB  - OBJECTIVE: To explore the possible effect of transforming growth factor-beta(1)
      (TGF -beta(1)) on the development of renal fibrosis in human mesengial
      proliferative glomerulonephritis (MsPGN). METHODS: Immunohistochemistry method,
      sirius red staining polarization microscopy and the computer imaging analysis
      system were used to detect the expression of TGF-beta(1), the distribution of
      collagen I, collagen III and collagen IV. RESULT: In MsPGN with renal fibrosis,
      collagen IV was increased markedly,and collagen I and collagen III appeared in
      the expanded mesengial matrix abnormally. Collagen III and collagen IV were
      increased markedly in tubulointerstitium. TGF-beta(1) expression was positively
      correlated with the expression of collagen I, collagen III and collagen IV in
      tubulointerstitium (r=0.82 0.92,P<0.01), and negatively correlated with I/III,
      I/IV and III/IV (r=-0.83,-0.92, P<0.001). CONCLUSION: Abnormal increase of TGF
      beta(1) may be one of the important factors associated with glomerular sclerosis
      and tubulointerstitial fibrosis through the increment and abnormal distribution
      of collagen I, collagen III and collagen IV.

PMID- 14966941
TI  - [TGF-beta1mRNA levels in renal cortex and peripheral blood mononuclear cells of
      diabetic rats].
AB  - OBJECTIVE: To investigate the effect of hyperglycemia and pioglitazone on TGF
      beta(1) gene expression in peripheral blood mononuclear cells (PBMC) and renal
      cortex, and the correlation of TGF-beta(1)mRNA levels between PBMC and renal
      cortex in STZ induced diabetic rats. METHODS: Fifty-four Sprague-Dawley rats were
      randomly divided into three groups: 18 normal control rats (group C), 18 diabetic
      rats (group D) and 18 diabetic rats treated with pioglitazone (20 mg x kg(-1)x d(
      1), group DP). Six rats from each group were sacrificed at 2, 4, 8 weeks. TGF
      beta(1)mRNA levels of PBMC and renal cortex were examined by RT-PCR+Slit
      hybridization analysis. RESULT: TGF-beta(1)mRNA level of renal cortex in group D
      was significantly higher than that in group C at each time point (P<0. 05); TGF
      beta(1)mRNA level of PMBC in group D was slightly higher than that of group C at
      4 weeks, and significantly higher at 8 weeks (P=0.01). There was positive
      correlation of TGF -beta(1)mRNA level between PBMC and renal cortex before
      (r=0.83, P=0.02) and after pioglitazone treatment at 8 weeks (r=0.82, P=0.03).
      CONCLUSION: TGF-beta(1)mRNA level of PBMC may reflect the change of TGF-beta(1)
      gene expression of renal cortex in diabetic rats.

PMID- 14966942
TI  - [Early expression of TGF-beta1, vimentin and desmin genes in renal cortex of
      diabetic rats].
AB  - OBJECTIVE: To study the expression of TGF-beta(1)vimentin and desmin in the renal
      cortex of diabetic rats induced by STZ. METHODS: Diabetes was induced in 24 male
      SD rats by single intraperitoneal injection of 1.0%STZ (70 mg/kg). Twenty-four
      age, weight and sex matched SD rats were used as controls. The expression of TGF
      beta(1),vimentin and desmin mRNA in the renal cortex were detected by RT-PCR on
      the 3rd, the 7th, the 14th and the 30th day after the DM rat model established.
      RESULT: (1)The expression of TGF-beta(1), vimentin mRNA in the renal cortex of
      diabetic rats gradually increased respectively from the 7th day and the 14th day
      after the model established, and the expressive intensity was significantly
      greater than that in controls (P<0.05 or P<0.01). However,the expression of
      desmin mRNA in the renal cortex of diabetic rats gradually decreased from the
      14th day after the model established, and the expressive intensity was
      significantly less than that in controls (P<0. 05 or P<0.01). (2) The expression
      of TGF-beta(1)mRNA correlated positively to that of vimentin mRNA (r 0.740
      P=0.000), while the expression of desmin mRNA correlated negatively to that of
      TGF-beta(1)mRNA (r 0.695 P=0.000) and to that of vimentin mRNA (r 0.591 P=0.002).
      CONCLUSION: The expression of renal cortical TGF-beta(1) and vimentin mRNA
      gradually increase while the expression of desmin mRNA gradually decrease during
      the first month of the diabetic model established suggest TGF-beta(1) may play a
      role in the transformation of renal tubular epithelial cells into fibroblast
      during the progressive interstitial fibrosis of diabetic nephropathy.

PMID- 14966943
TI  - [Association of serum sex hormone-binding globulin with type 2 diabetes].
AB  - OBJECTIVE: To explore the changes of serum sex hormone-binding globulin (SHBG)
      and sex hormone levels in type 2 diabetes and to explore the correlation of SHBG
      with blood glucose, BMI, insulin sensitivity and the intervention of
      pioglitazone. METHODS: Eighty-five cases with type 2 diabetes (38 women) and 59
      normal controls (27 women) were recruited randomly in the study. Among all
      patients 48 underwent pioglitazone intervention. All women were postmenopausal.
      Fasting serum samples were taken separately. SHBG were measured with IRMA, and
      estrogen (E2), testosterone (T), fasting insulin (FINS ) were detected with RIA.
      Body weight, fasting blood glucose (FBG), blood lipids,BMI, HOMA-IS were measured
      and calculated as well. LN [1/ (FBG x FINS)] was used as insulin sensitivity
      index (ISI). RESULT: Patient groups had lower serum SHBG levels than control
      groups of both sexes (women, P<0.01; men, P<0.05). T/SHBG are higher in women
      patient group compared with control (P<0.01). Spearman analysis showed that in
      women patient group,serum SHBG was correlated with FBG, FINS and ISI (r(s)=-0.372
      P<0.05; 0.332 P<0.05; 0.445 P<0.01). While in men patient group,BMI was
      negatively correlated with serum SHBG and total T (r(s)= 0.329 P<0.05 and-0.424
      P<0.01). Significant improvements of blood glucose and lipids were demonstrated
      in patients after 12-week pioglitazone intervention compared with baseline
      values, while serum SHBG, sex hormones and ISI had not significantly changed.
      CONCLUSION: Reduced serum SHBG of patients with type 2 diabetes might be related
      to insulin resistance to some extent.

PMID- 14966944
TI  - [Experimental study on attachment of bacillus Calmette-Guerin to bladder wall
      with different types of injury].
AB  - OBJECTIVE: To investigate whether different types of injury on bladder wall can
      influence bacillus Calmette-Guerin (BCG) attachment. METHODS: The bladder mucosa
      of 24 rabbits were treated by electrocautery,cryocautery and incision on left
      lateral wall, right lateral wall and posterior wall, respectively. Then
      radiolabeled BCG ((3)H-BCG) was instilled into bladder. Two hours latter, the
      injured bladder wall with different methods and non-injured wall (anterior wall
      of bladder) were surgically removed and digested. The quantity of BCG of each
      specimen was determined by liquid scintillation counter. RESULT: The quantity of
      BCG attachment to bladder wall with different injuries was significantly higher
      than that of non-injured wall (P<0.001), meanwhile there was no statistically
      difference among the BCG levels of different injury types (P>0.05). CONCLUSION:
      BCG attachment is not influenced by different types of injury on the bladder
      wall.

PMID- 14966945
TI  - [Inhibition effect of arsenic trioxide on the growth of human MDS cell line MUTZ
      1 cells].
AB  - OBJECTIVE: To investigate the inhibition effect of arsenic trioxide (AS(2)O(3))
      on the growth of human MDS-RAEB cell line MUTZ-1 cells and to explore the
      possible cellular and molecular mechanisms. METHODS: The apoptosis and
      differentiation of MUTZ-1 cells induced by AS(2)O(3) solution of different
      concentrations were studied with cell morphology, MTT, DNA fragmentation assay,
      RT-PCR, Nitroblue tetrazolium (NBT) reduction method and flow cytometry. RESULT:
      (1) Low concentration ofAS(2)O(3) (0.05 - 0.25 micromol/L) had no marked growth
      inhibition effect on MUTZ-1 cells; after 14 d treatment, it down-regulated the
      expression of positive cell differentiation antigens CD38, CD7, CD10, HLA-DR
      (P<0.05), but did not up-regulate the expression of CD11b (P>0.05). (2) After
      treatment with 1.0 - 20.0 micromol/L of AS(2)O(3), MUTZ-1 cells presented typical
      features of apoptosis with a dose dependent manner (r=-0.999, P<0.05). The
      expression of bcl-2 mRNA and the ration of bcl-2/bax were decreased after
      AS(2)O(3) treatment (P<0.05). CONCLUSION: Low concentration of (2)O(3) may have
      partial differentiation inducement on MUTZ-1 cells. With a certain range of dose
      (1.0 - 20.0 micromol/L), (2)O(3) can induce apoptosis of MUTZ-1 cells. (2)O(3)
      can significantly down-regulate bcl-2 and it might be one of the mechanisms of
      (2)O(3) treatment.

PMID- 14966946
TI  - [Combined surgery for cataract and glaucoma: phacoemulsification, foldable
      intraocular lens implantation and viscocanalostomy].
AB  - OBJECTIVE: To assess the outcome of phacoemulsification-intraocular lens (IOL)
      implantation combined with viscocanalostomy (P-C group), compared with that of
      phacoemulsification-IOL implantation combined with trabeculectomy (P-T group).
      METHODS: Combined phacoemulsification with corneal incision, foldable intraocular
      lens implantation and viscocanalostomy was performed in 21 eyes of 19 cataract
      patients with primary open-angle glaucoma. All patients were followed up for 3 -
      6 months. RESULT: Intraocular pressure (IOP) was significantly lower in both P-C
      group and P-T group (P=0.000). There was no statistically significant difference
      between two groups. Visual outcome was similar in both groups. Complications of P
      C group included Descemet's membrane puncture in 2 eyes, Schlemm's tube puncture
      in 2 eyes and IOP spikes in 3 eyes (at 24 hours postoperatively). The P-C group
      experienced significantly less inflammation than the P-T group. CONCLUSION:
      Phacoemulsification-IOL implantation combined with viscocanalostomy is a safe and
      effective surgery, with lower complicatin rate and easier ambulatory care.

PMID- 14966947
TI  - [An improved novel method of venlafaxine synthesis].
AB  - OBJECTIVE: To synthesize venlafaxine with an improved novel method. METHODS: p
      methoxypheny  lethyl-acid was reacted with SOCl(2) to produce acyl chloride 
      which was reacted with N,N-dimethylamine solution to get amide; then through
      Ivanov reaction and reduction by KBH(4)/BF(3).Et(2)O to yield venlafaxine.
      RESULT: Venlafaxine was successfully synthesized by using this method with an
      yield rate of 50.3%. CONCLUSION: The improved method is suitable for industrial
      production of venlafaxine.

PMID- 14966948
TI  - [Effects of intravitreal irrigation with BSS or Bss Plus solution on the retina
      and corneal].

PMID- 14966949
TI  - [Laparoscopic diagnosis and treatment of cryptorchidism with impalpable testis].

PMID- 14966950
TI  - [Progress of study on the structure and function of omega-conotoxins].

PMID- 14966951
TI  - The theoretical 77Se chemical shift as a probe of selenium state in
      selenoproteins and their mimics.
AB  - Theoretical 77Se chemical shifts of a series of simple organoselenium compounds
      are compared to known NMR data for various derivatives of selenoenzymes and
      selenoamino acids. Since the theoretical data only differs from the biochemical
      data set by an overall approximately 15-30 ppm downfield shift, simple
      theoretical model studies are suggested as an additional tool for the
      interpretation of selenoenzyme spectra. Further studies demonstrate that model
      systems can be extended to incorporate the effects of intramolecular interactions
      (such as Se.N bonds).

PMID- 14966952
TI  - Chiral recognition of amino acids and dipeptides by a water-soluble zinc
      porphyrin.
AB  - A chiral water-soluble zinc porphyrin was optically resolved on a chiral HPLC
      column, and the binding of chiral amino acids and peptides to each of the
      enantiomers was examined spectrophotometrically in basic aqueous solution. The
      binding data apparently indicated that the zinc porphyrin has chiral selectivity
      for amino acids and dipeptides. This was reasonably explained in terms of the
      triple cooperation of coordination, Coulomb, and steric interactions of the
      chiral amino carboxylates with the porphyrin. A compensatory relationship among
      the thermodynamic parameters for chiral recognition was also shown.

PMID- 14966953
TI  - NaRuO2 and NaxRuO2.yH2O: new oxide and oxyhydrate with two dimensional RuO2
      layers.
AB  - The new oxide and oxyhydrate NaRuO2 and NaxRuO2.yH2O (x = 0.22, y = 0.45) have
      been characterized. NaRuO2 is isostructural with alpha-NaFeO2. The symmetry is
      rhombohedral (R3m space group) with lattice parameters of a = 3.018(2) A and c =
      16.493(3) A. The structure has been refined by the Rietveld method. The
      oxyhydrate NaxRuO2.yH2O has been prepared by stirring a sample of NaRuO2 in water
      at ambient temperature. NaxRuO2.yH2O crystallizes in the space group R3m with
      lattice parameters of a = 2.930(2) A and c = 21.913(5) A. The structure is
      related to the CuFeO2 3R polytype structure with the AABBCC sequence of the
      oxygen close packed layers along the c-axis. Analogies with the related cobalt
      phases are discussed. The susceptibilities of NaRuO2 and NaxRuO2.yH2O are small
      and constant in a large temperature range.

PMID- 14966954
TI  - Synthesis and structural characterization of a terminal hydroxide containing
      alumoxane via hydrolysis of aluminum hydrides.
AB  - A novel terminal hydroxide containing dinuclear alumoxane LAl(OH)OAlL(OCH=N-tBu)
      (3; L = HC(CMeNAr)2, Ar = 2,6-iPr2C6H3) was prepared by treatment of aluminum
      dihydride LAlH2 (1) and tert-butyl isocyanate in the presence of trace amounts of
      water and alternatively from 1 and LAlH(OCH=N-tBu) (2) with water. Compound 2 was
      obtained from the reaction of 1 and tert-butyl isocyanate.

PMID- 14966955
TI  - Calix[4]pyrrole Schiff base macrocycles. Novel binucleating ligands for mu-oxo
      iron complexes.
AB  - New bimetallic mu-oxo diferric complexes of several previously reported
      calix[4]pyrrole Schiff base macrocycles are described. The synthesis of a new
      member of this class of macrocycles is also reported; it was prepared via an acid
      catalyzed condensation between 1,9-bisformyl-5,5-dipropyldipyrromethane and o
      phenylenediamine. Reactions of the free base macrocycles or their bis-HCl salts
      with Fe(II) mesitylene, followed by air oxidation, gave the binuclear mu-oxo bis
      Fe(III) compounds 6-10 in moderate yield. X-ray crystallography data reveal two
      different coordination environments for the Fe-O-Fe subunit in 6-10 that it is
      suggested can be controlled by altering the reaction conditions. Structural
      properties of these metalated pyrrolic macrocycles are also compared to those of
      mu-oxo diferric porphyrins and mu-oxo diferric texaphyrin. Complexes 6-10 exhibit
      two distinct types of M-N bonds that are similar in length to the bonds observed
      in metallotexaphyrin complexes. However, the electronics of the present systems
      are very different from those of texaphyrins and porphyrins in that no
      delocalized bonding patterns are observed within the ligands as a whole.

PMID- 14966956
TI  - Determination of the antimony valence state in Eu10Mn6Sb13.
AB  - The antimony-121 Mossbauer spectra of Eu10Mn6Sb13 have been measured between 2
      and 295 K. Although the Zintl formalism indicates that the nine
      crystallographically distinct antimony sites in Eu10Mn6Sb13 should have formal
      valence states of -2, -1, 0, and +1, the Mossbauer spectral isomer shifts reveal
      that the valence states of the different sites are all quite similar and
      correspond to an average electronic configuration for antimony of 5s(1.7)5p(4.0).
      This configuration corresponds to an excess of negative charge on the antimony of
      0.7 or an average valence of -0.7, a valence which is rather consistent with the
      average antimony valence of -0.61 obtained from the Zintl formalism for the nine
      antimony sites in Eu10Mn6Sb13. The spectra obtained between 90 and 295 K are more
      consistent with the absence rather than the presence of any transferred magnetic
      hyperfine field at the antimony. In contrast, the spectra obtained at 2 and 5 K
      reveal the presence of an average transferred magnetic hyperfine field of ca. 8
      T, a field that arises from the ferromagnetic ordering of the near-neighbor
      manganese(II) ions.

PMID- 14966957
TI  - Accurate redetermination of the X-ray structure and electronic bonding in
      adenosylcobalamin.
AB  - The electronic structure of adenosylcobalamin (B12 coenzyme, AdoCbl) has been
      calculated by a density functional method, using the orthogonalized linear
      combination of the atomic orbital method (OLCAO). Since a fixed accurately
      determined geometry was needed in such calculations, the crystal structure of
      adenosylcobalamin has been redone and refined to R = 0.065, using synchrotron
      diffraction data. Comparison with the recently reported electronic structures of
      cyano- (CNCbl) and methylcobalamin (MeCbl) shows that the net charges and bond
      orders vary only on the axial donors. The values in the three cobalamins suggest
      that the Co-C bond in MeCbl has a strength similar to that in AdoCbl, but it is
      significantly weaker that that in CNCbl. Present results are compared with those
      previously reported for the analogous corrin derivatives; i.e., simplified
      cobalamins with the side chains a-f replaced by H atoms. Despite a qualitative
      agreement, a discrepancy in the calculated HOMO-LUMO gap is found.

PMID- 14966958
TI  - Heteroleptic copper dipyrromethene complexes: synthesis, structure, and
      coordination polymers.
AB  - The synthesis of neutral [Cu(dpm)2] and [Cu(dpm)(acac)] (dpm = dipyrromethene,
      acac = acetylacetonato) complexes is presented. The formation of the asymmetric
      metal complexes was monitored by electronic absorption and infrared spectroscopy.
      Two of the complexes investigated, containing pyrdpm ligands (pyrdpm =
      pyridyldipyrromethene), form 1-dimensional coordination polymers. The
      coordination polymers formed by these complexes have been characterized by single
      crystal X-ray diffraction, differential scanning calorimetry, and
      thermogravimetric analysis. The complexes possess square pyramidal coordination
      geometries with the apical position occupied by the meso-pyridyl donor of a
      neighboring complex in the crystal lattice. The features of these coordination
      complexes that facilitate formation of extended solids have been probed.
      Symmetric [Cu(pyrdpm)2] complexes are unable to form coordination solids due to
      steric hindrance at the metal center. Use of cyano donors in complexes such as
      [Cu(cydpm)(acac)] (cydpm = cyanodipyrromethene) in lieu of pyridyl donors also
      fail to form network solids. Through these systematic studies, both the basic
      coordination chemistry of these complexes and the fundamental design requirements
      for synthesizing this novel class of coordination polymers have been defined.

PMID- 14966959
TI  - Syntheses and solid-state and solution structures of [Ba[(C5Me5)2Ti2F7]2(hmpa)]
      and [Ba8Ti6F30I2(C5Me5)6(hmpa)6][I3]2.
AB  - The complexes [Ba[(C5Me5)2Ti2F7]2(hmpa)].(THF), 1.hmpa.(THF), and
      [Ba8Ti6F30I2(C5Me5)6(hmpa)6][I3]2.10(THF), 2[I3]2.10(THF), were prepared from
      [Hdmpy](+)[(C5Me5)2Ti2F7]- (dmpy = 2,6-dimethylpyridine), BaI2, and hmpa (hmpa =
      hexamethylphosphoramide). They were characterized by 1H and 19F NMR and IR
      spectroscopy and examined by single-crystal X-ray crystallography. The
      complexation equilibrium of the barium ion in 1 with hmpa and the dynamics of the
      barium ion moving on the fluorine surfaces of [(C5Me5)2Ti2F7]- in 1.hmpa have
      been studied by variable-temperature 19F NMR spectroscopy. The core of the
      complex 2[I3]2.10(THF) resembles the basic structural unit of the cubic
      perovskite.

PMID- 14966960
TI  - Syntheses and structural, physical, and theoretical studies of the novel
      isostructural Mo9 cluster compounds Ag(2.6)CsMo9Se11, Ag(4.1)ClMo9Se11, and h
      Mo9Se11 with tunnel structures.
AB  - The new isostructural compounds Ag(2.6)CsMo9Se11 (1) and Ag(4.1)ClMo9Se11 (2)
      were prepared by solid-state reaction in evacuated sealed silica tubes at 1200
      degrees C and 860 degrees C, respectively. By topotactic reduction-oxidation
      reaction of Ag(4.1)ClMo9Se11 with I2, we also obtained the metastable compound h
      Mo9Se11 (3). The three compounds crystallize in the hexagonal space group
      P6(3)/m, Z = 2, (1) a = 10.0472(2) A, c = 11.9548(2), (2) a = 10.0321(2) A, c =
      11.8734(2) A, and (3) a = 9.4204(2) A, c = 12.1226(2) A. Their crystal structures
      were determined from single-crystal X-ray diffraction data and consist of
      interconnected Mo9Se11 units forming an original and unprecedented three
      dimensional framework in which large tunnels are occupied randomly by a part of
      the Ag+ and the Cl- ions in 2 and the Cs+ ions in 1, the remaining Ag+ in 1 being
      localized in mirror planes around the 3-fold axis. First-principle calculations
      allow the understanding of the variation of the atomic distances. Electrical
      resistivity measurements carried out on single crystals of Ag(2.6)CsMo9Se11 and
      Ag(4.1)ClMo9Se11 in which the number of electrons per Mo9 cluster is different
      indicate that the former is semiconducting whereas the latter is semimetallic.

PMID- 14966961
TI  - A novel cadmium aminophosphonate: X-ray powder diffraction structure, solid-state
      IR and NMR spectroscopic determination of the fine structure of the organic
      moieties.
AB  - A new divalent cadmium phosphonate, Cd2Cl2(H2O)4(H2L), has been synthesized from
      the ethylenediamine-N,N'-bis(methylenephosphonic acid) (H4L). The obtained
      microcrystalline compound has been characterized by solid-state IR spectra and
      13C, 31P, and 113Cd CP MAS NMR. The static 13P NMR spectra have been also
      recorded to give the delta11, delta22, and delta33 chemical shift parameters for
      both compounds. The spectral data, collected for Cd2Cl2(H2O)4(H2L), are in an
      agreement with its X-ray powder diffraction structure solved with the cell
      dimensions a = 16.6105(10), b = 7.1572(4), and c = 6.8171(4) A and beta =
      98.327(4) degrees. The octahedral coordination sphere of the cadmium atoms
      consists of two phosphonate oxygen atoms, two water oxygen atoms, and the two
      chlorine atoms. Cadmium atoms are bridged by the chlorine atoms forming four
      membered rings. The phosphorus atoms exhibit a tetrahedral coordination with two
      oxygen atoms bonded to the cadmium atoms with P-O distances of 1.503(10) and
      1.504(10) A. The third oxygen atom, showing a longer P-O distance (1.546(9) A),
      is not bonded to the metal center, nor is it bonded to a proton. The combined IR
      and NMR proton-phosphorus cross-polarization kinetic data together with the X-ray
      data confirm that the cadmium phosphonate has the zwitterionic structure
      (NH2(+)CH2P(O2Cd2)O-) similar to the initial aminophosphonic acid H4L.

PMID- 14966962
TI  - Structure, energetics, and bonding of first row transition metal pentazolato
      complexes: a DFT study.
AB  - Quantum chemical calculations with gradient-corrected (B3LYP) density functional
      theory for the mono- and bispentazolato complexes of the first row transition
      metals (V, Cr, Mn, Fe, Co, and Ni), the all-nitrogen counterparts of
      metallocenes, were performed, and their stability was investigated. All possible
      bonding modes (e.g. eta1, eta2, eta3, and eta5) of the pentazolato ligand to the
      transition metals have been examined. The transition metal pentazolato complexes
      are predicted to be strongly bound molecules. The computed total bond
      dissociation enthalpies that yield free transition metal atoms in their ground
      states and the free pentazolato ligands were found in the range of 122.0-201.9
      (3.7-102.3) kcal mol(-1) for the bispentazolato (monopentazolato) complexes,
      while those yielding M2+ and anionic pentazolato ligands were found in the range
      of 473.2-516.7 (273.6-353.5) kcal mol(-1). The electronic ground states of
      azametallocenes along with their spectroscopic properties (IR, NMR, and UV-vis)
      obtained in a consistent manner across the first transition metal series provide
      means for discussion of their electronic and bonding properties, the
      identification of the respective azametallocenes, and future laboratory studies.
      Finally, exploring synthetic routes to azametallocenes it was found that a [2 +
      3] cycloaddition of dinitrogen to a coordinated azide ligand with nickel(II) does
      not seem to provide a promising synthetic route for transition metal pentazolato
      complexes while the oxidative addition of phenylpentazole and fluoropentazole to
      Ni(0) bisphosphane complexes merits attention for the experimentalists.

PMID- 14966963
TI  - Preparation of acentric porous coordination frameworks from an interpenetrated
      diamondoid array through anion-exchange procedures: crystal structures and
      properties.
AB  - The formation, crystal structures, and properties of a series of three
      dimensional (3-D) Cu(II) coordination polymers,
      [[Cu(L)2(H2O)2](PF6)2(H2O)(1.25)]n (1), [[CuL(N3)2](H2O)(1.5)]n (2), and
      [[CuL(H2O)(SO4)](H2O)2]n (3), with an angular bridging ligand 2,5-bis(4-pyridyl)
      1,3,4-oxadiazole (L) are reported. Complex 1 crystallizes in the tetragonal
      I4(1)/a space group (a = b = 13.462(2) A, c = 46.47(1) A, Z = 8), complex 2 in
      the orthorhombic Pna2(1) space group (a = 6.379(2) A, b = 10.060(3) A, c =
      27.232(9) A, Z = 4), and complex 3 in the orthorhombic P2(1)2(1)2(1) space group
      (a = 5.510(2) A, b = 10.576(4) A, c = 28.34(1) A, Z = 4). Different polymeric
      frameworks are obtained by only varying the counterions. These include the 2-fold
      interpenetrated diamondoid structure of 1, the acentric alpha-Po network of 2,
      and the chiral open framework of 3 with (6(3)).(6(9).8) topology. The interesting
      anion-exchange, porous, and magnetic properties of these coordination
      supramolecules have been investigated in detail.

PMID- 14966964
TI  - New lanthanide complexes for sensitized visible and near-IR light emission:
      synthesis, 1H NMR, and X-ray structural investigation and photophysical
      properties.
AB  - We describe the syntheses, the 1H NMR studies in CD3OD and D2O as solvent, the X
      ray characterization, and the luminescence properties in D2O solution of the two
      complexes Eu.1 and Er.1, where 1 is a dipartite ligand that includes (i) a
      1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) unit serving as
      hosting site for the metal center; and (ii) a phenanthroline unit which plays the
      role of light antenna for the sensitization process of the metal centered
      luminescence. In a previous report (Inorg. Chem. 2002, 41, 2777), we have shown
      that for Eu.1 there are no water molecules within the first coordination sphere.
      X-ray and 1H NMR results reported here are consistent with full saturation of the
      nine coordination sites within the Eu.1 and Er.1 complexes. In addition, these
      studies provide important details regarding the conformations, square antiprism
      (SAP) and twisted square antiprism (TSAP), adopted in solution by these
      complexes. The luminescence results are consistent with both an effective
      intersystem crossing (ISC) at the light absorbing phenanthroline unit
      (lambda(exc) = 278 nm) and an effective energy transfer (en) process from the
      phenanthroline donor to the cation acceptor (with unit or close to unit
      efficiency for both steps). In D2O solvent, the overall sensitization efficiency,
      phi(se), is 0.3 and 5 x 10(-6), for Eu.1 (main luminescence peaks at 585, 612,
      699 nm) and Er.1 (luminescence peak at 1530 nm), respectively. The photophysical
      properties of both complexes are discussed with reference to their structural
      features as elucidated by the obtained 1H NMR and X-ray results.

PMID- 14966965
TI  - An expanded set of functional groups in bis(dithiolene)tungsten(IV,VI) complexes
      related to the active sites of tungstoenzymes, Including WIV-SR and WVI-O(SR).
AB  - The active sites of tungstoenzymes have the formulations W(IV,V)L(S(2)pd)(2) and
      W(VI)LL'(S(2)pd)(2), in which two pyranopterindithiolene cofactor ligands
      (S(2)pd) are chelated to a tungsten atom. Ligands L and/or L' are not fully
      defined in any wild-type enzyme. The feasibility of various coordination
      fragments (functional groups) in potential bis(dithiolene)tungsten site analogues
      has been examined in previous work by exploratory synthesis. This investigation
      expands the range of accessible functional groups. The synthetic scheme
      originates with [W(CO)(2)(S(2)C(2)Me(2))(2)], whose carbonyl groups are labile to
      substitution. Complexes [W(IV,VI)LL'(S(2)C(2)Me(2))(2)](1-) are described in
      terms of their functional groups W(IV,VI)LL'. Reaction of the dicarbonyl with
      formate in acetonitrile/THF affords W(IV)(CO)(eta(1)-HCO(2)) (4) and in Me(2)SO
      W(VI)O(eta(1)-HCO(2)) (7) by an oxo transfer reaction. Carboxylates yield six
      coordinate W(IV)(eta(2)-O(2)CR) (1-3, R = Ph, Me, Bu(t)) with C(2)(v) symmetry.
      Reaction of 3 (R = Bu(t)) with Me(3)SiSR (R = C(6)H(2)-2,4,6-Pr(i)(3)) gives
      W(IV)(SR) (5), which undergoes oxo and sulfido atom transfer to form W(VI)O(SR)
      (8) and W(VI)S(SR) (9), respectively. Attempts to prepare corresponding
      selenolate complexes, pertinent to the active site of formate dehydrogenase, were
      unsuccessful, including reactions of W(VI)OCl (10) with RSe(-). Structure proofs
      of 2-10 were obtained by X-ray structure determinations. Some 26 functional group
      types in bis(dithiolene)W(IV,V,VI) molecules have now been achieved by synthesis.
      It remains to be seen which are incorporated in an enzyme site. A number of them
      (e.g., 5) are directly analogous to molybdoenzyme sites, and may possess
      corresponding reactivity with biological substrates, as do W(IV)(OR)/W(VI)O(OR)
      (prepared earlier) in the reduction of N- and S-oxides by atom transfer.

PMID- 14966966
TI  - Metal ion-binding properties of (1H-benzimidazol-2-yl-methyl)phosphonate (Bimp2-)
      in aqueous solution. Isomeric equilibria, extent of chelation, and a new
      quantification method for the chelate effect.
AB  - The acidity constants of the 2-fold protonated (1H-benzimidazol-2-yl
      methyl)phosphonate, H2(Bimp)(+/-), are given, and the stability constants of the
      M(H;Bimp)+ and M(Bimp) complexes with the metal ions M2+ = Mg2+, Ca2+, Ba2+,
      Mn2+, Co2+, Cu2+, Zn2+, or Cd2+ have been determined by potentiometric pH
      titrations in aqueous solution at I = 0.1 M (NaNO3) and 25 degrees C. Application
      of previously determined straight-line plots of log KM(M(Bi-R)) versus pKH(H(Bi
      R)) for benzimidazole-type ligands, Bi-R, where R represents a residue which does
      not affect metal ion binding, proves that the primary binding site in the
      M(H;Bimp)+ complexes is (mostly) N3 and that the proton is located at the
      phosphonate group; outersphere interactions seem to be important, and the degree
      of chelate formation is above 60% for all metal ion complexes studied, except for
      Zn(H;Bimp)+. A similar evaluation based on log KM(M(R-PO3)) versus pKH(H(R-PO3))
      straight-line plots for simple phosph(on)ate ligands, R-, where R represents a
      residue which cannot participate in the coordination process, reveals that the
      primary binding site in the M(Bimp) complexes is (mostly) the phosphonate group
      with all metal ions studied. In this case, the formation degree of the chelates
      varies more widely in dependence on the kind of metal ion involved, i.e., from 17
      +/- 11% to nearly 100% for Ba(Bimp) and Cu(Bimp), respectively. For all the
      M(H;Bimp)+ and M(Bimp) systems, the intramolecular equilibria between the
      isomeric complexes are evaluated in a quantitative manner. The fact that for
      Bimp2- the metal ion affinity of the two binding sites, N3 and PO3(2-), can be
      calculated independently, i.e., the corresponding micro stability constants
      become known, allows us to present for the first time a method for the
      quantification of the chelate effect solely based on comparisons of stability
      constants which carry the same dimensions. This effect is often ill defined in
      textbooks because equilibrium constants of different dimensions are compared,
      which is avoided in the present case. For the M(Bimp) complexes, it is shown that
      the chelate effect is close to zero for Ba(Bimp) whereas for Cu(Bimp) it amounts
      to about four log units. This method is also applicable to other chelating
      systems. Finally, considering that benzimidazole as well as phosphonate
      derivatives are employed as therapeutic agents, the potential biological
      properties of Bimp, especially regarding nucleic acid polymerases, are briefly
      discussed.

PMID- 14966967
TI  - First octameric ellipsoid lanthanide(III) complexes: crystal structure and
      nonlinear optical absorptive and refractive properties.
AB  - The ligand N,N'-bis(1,3,4-thiobiazolyl)-2,6-pyridyldicarboxamide (btapca) has
      been synthesized and its coordination properties toward La(III) and Ce(III) in
      the presence of air have been investigated. The complexes
      [Ln8(tbzcapc)12(H2O)24].6DMF (Ln = La, 1, Ce, 2; tbzcapc = 6-[2-N-(1,3,4
      thiabiazolyl)carboxamido]-2-pyridylcarboxylate) show octameric ellipsoid
      structures. We found the starting ligand btapca had been altered into tbzcapc
      during the formation process of [Ln8(tbzcapc)12(H2O)24].6DMF. The NLO properties
      of complexes 1 and 2 were investigated via Z-scan techniques. It is interesting
      that the two isostructural complexes show completely different NLO properties.
      Complex 1 shows NLO refractive effects without absorption, while complex 2
      possesses NLO absorptive behavior without refraction.

PMID- 14966968
TI  - Preparation and reactivity of mixed-ligand iron(II) hydride complexes with
      phosphites and polypyridyls.
AB  - Hydride complexes [FeH(N-N)P3]BPh4 (1, 2) [N-N = 2,2'-bipyridine (bpy) and 1,10
      phenanthroline (phen); P = P(OEt)4, PPh(OEt)2, and PPh2OEt] were prepared by
      allowing FeCl2(N-N) to react with phosphite in the presence of NaBH4. The
      hydrides [FeH(bpy)2P]BPh4 (3) [P = P(OEt)3 and PPh(OEt)2] were prepared by
      reacting the tris(2,2'-bipyridine) [Fe(bpy)3]Cl2.5H2O complex with the
      appropriate phosphite in the presence of NaBH4. The protonation reaction of 1 and
      2 with acid was studied and led to thermally unstable (above -20 degrees C)
      dihydrogen [Fe(eta2-H2)(N-N)P3]2+ (4, 5) derivatives. The presence of the H2
      ligand is indicated by short T(1 min) values (3.1-3.6 ms) and by J(HD)
      measurements (31.2-32.5 Hz) of the partially deuterated derivatives. Carbonyl
      [Fe(CO)(bpy)[P(OEt)3]3](BPh4)2 (6) and nitrile [Fe(CH3CN)(N-N)P3](BPh4)2 (7, 8)
      [N-N = bpy, phen; P = P(OEt)3 and PPh(OEt)2] complexes were prepared by
      substituting the H2 ligand in the eta2-H2 4, 5 derivatives. Aryldiazene complexes
      [Fe(ArN=NH)(N-N)P3](BPh4)2 (9, 10, 11) (Ar = C6H5, 4-CH3C6H4) were also obtained
      by allowing hydride [FeH(N-N)P3]BPh4 derivatives to react with aryldiazonium
      cations in CH2Cl2 at low temperature.

PMID- 14966969
TI  - Preparation and reactivity of mixed-ligand ruthenium(II) hydride complexes with
      phosphites and polypyridyls.
AB  - Chloro complexes [RuCl(N-N)P3]BPh4 (1-3) [N-N = 2,2'-bipyridine, bpy; 1,10
      phenanthroline, phen; 5,5'-dimethyl-2,2'-bipyridine, 5,5'-Me2bpy; P = P(OEt)3,
      PPh(OEt)2 and PPh2OEt] were prepared by allowing the [RuCl4(N-N)].H2O compounds
      to react with an excess of phosphite in ethanol. The bis(bipyridine)
      [RuCl(bpy)2[P(OEt)3]]BPh4 (7) complex was also prepared by reacting
      RuCl2(bpy)2.2H2O with phosphite and ethanol. Treatment of the chloro complexes 1
      3 and 7 with NaBH4 yielded the hydride [RuH(N-N)P3]BPh4 (4-6) and
      [RuH(bpy)2P]BPh4 (8) derivatives, which were characterized spectroscopically and
      by the X-ray crystal structure determination of [RuH(bpy)[P(OEt)3]3]BPh4 (4a).
      Protonation reaction of the new hydrides with Bronsted acid was studied and led
      to dicationic [Ru(eta2-H2)(N-N)P3]2+ (9, 10) and [Ru(eta(2-H2)(bpy)2P]2+ (11)
      dihydrogen derivatives. The presence of the eta2-H2 ligand was indicated by a
      short T(1 min) value and by the measurements of the J(HD) in the [Ru](eta2-HD)
      isotopomers. From T(1 min) and J(HD) values the H-H distances of the dihydrogen
      complexes were also calculated. A series of ruthenium complexes, [RuL(N
      N)P3](BPh4)2 and [RuL(bpy)2P](BPh4)2 (P = P(OEt)3; L = H2O, CO, 4-CH3C6H4NC,
      CH3CN, 4-CH3C6H4CN, PPh(OEt)2], was prepared by substituting the labile eta2-H2
      ligand in the 9, 10, 11 derivatives. The reactions of the new hydrides 4-6 and 8
      with both mono- and bis(aryldiazonium) cations were studied and led to
      aryldiazene [Ru(C6H5N=NH)(N-N)P3](BPh4)2 (19, 21), [[Ru(N-N)P3]2(mu-4,4'-NH=NC6H4
      C6H4N=NH)](BPh4)4 (20), and [Ru(C6H5N=NH)(bpy)2P](BPh4)2 (22) derivatives. Also
      the heteroallenes CO2 and CS2 reacted with [RuH(bpy)2P]BPh4, yielding the formato
      [Ru[eta1-OC(H)=O](bpy)2P]BPh4 and dithioformato [Ru[eta1-SC(H)=S](bpy)2P]BPh4
      derivatives.

PMID- 14966970
TI  - New complexes of zirconium(IV) and hafnium(IV) with heteroscorpionate ligands and
      the hydrolysis of such complexes to give a zirconium cluster.
AB  - A series of zirconium and hafnium heteroscorpionate complexes have been prepared
      by the reaction of MCl4 (M = Zr, Hf) with the compounds [[Li(bdmpza)(H2O)](4)]
      [bdmpza = bis(3,5-dimethylpyrazol-1-yl)acetate], [[Li(bdmpzdta)(H2O)](4)]
      [bdmpzdta = bis(3,5-dimethylpyrazol-1-yl)dithioacetate], and (Hbdmpze) [bdmpze =
      2,2-bis(3,5-dimethylpyrazol-1-yl)ethoxide] (the latter with the prior addition of
      Bu(n)Li). Under the appropriate experimental conditions, mononuclear complexes,
      namely, [MCl3(kappa3-bdmpzx)] [x = a, M = Zr (1), Hf (2); x = dta, M = Zr (3), Hf
      (4); x = e, M = Zr (5), Hf (6)], and dinuclear complexes, namely, [[MCl2(mu
      OH)(kappa3-bdmpzx)]2] [x = a, M = Zr (7), Hf (8); x = dta, M = Zr (9); x = e, M =
      Zr (10)], were isolated. A family of alkoxide-containing complexes of the general
      formula [ZrCl2(kappa3-bdmpzx)(OR)] [x = a, R = Me (11), Et (12), iPr (13), tBu
      (14); x = dta, R = Me (15), Et (16), iPr (17), tBu (18); x = e, R = Me (19), Et
      (20), (i)Pr (21), (t)Bu (22)] was also prepared. Complexes 11-14 underwent an
      interesting hydrolysis process to give the cluster complex [Zr6(mu3
      OH)8(OH)8(kappa2-bdmpza)8] (23). The structures of these complexes have been
      determined by spectroscopic methods, and the X-ray crystal structures of 7, 8,
      and 23 were also established.

PMID- 14966971
TI  - Structural characterization, magnetic properties, and electrospray mass
      spectrometry of two Jahn-Teller isomers of the single-molecule magnet
      [Mn12O12(CF3COO)16(H2O)4].
AB  - The syntheses and characterization of two new, highly soluble, single-molecule
      magnets [Mn12O12(CF3COO16(H2O)4].2CF3COOH.4H2O (1) and
      Mn12O12(CF3COO16(H2O)4].CF3COOH.7H2O (2) are reported. Compound 1 was isolated
      from the reaction of Mn12O12(CF3COO16(H2O)4] with trifluoroacetic acid in CH2Cl2.
      Compound 1 crystallizes in the tetragonal space group Ifourmacr; (No. 82) with
      unit cell parameters a = b = 18.128(3) A, c = 13.048(3) A, V = 4287.9(19) A3, Z =
      2 and is isostructural to [Mn12O12(CH3COO)16(H2O)4]. Compound 2 was prepared from
      the reaction of Mn12O12(CF3COO16(H2O)4] with neat trifluoroacetic acid, and
      crystallizes in the monoclinic space group P2(1)/n (No. 14) with unit cell
      parameters a = 15.221(8) A, b = 21.870(12) A, c = 27.217(15) A, beta = 90.53(1)
      degrees, V = 9060(9) A3, and Z = 4. The dc magnetic susceptibility measurements
      in the 2-300 K temperature range support a high-spin ground state. The
      magnetization data collected in the 1-7 T field range from 1.8 to 4.0 K were best
      fit to the parameters S = 10, g = 2.15, D = -0.65 cm(-1), and E = 0 cm(-1) for 1
      and S = 10, g = 1.87, D = -0.34 cm(-1), and E = -0.10 cm(-1) for 2. The ac
      susceptibility data for compound 1 reveal out-of-phase (chi(m)") signals in the 4
      7 K temperature range, whereas the chi(m)" signals for compound 2 appear below
      temperatures of 4 K. This variation in blocking temperatures is a consequence of
      the two different crystallographic forms of compounds 1 and 2. Compound 1
      exhibits the same structural geometry and distortions found in
      [Mn12O12(CH3COO)16(H2O)4], while compound 2 is of lower molecular symmetry with
      two Jahn-Teller axes of distortion being oriented along oxide ligands. This
      different structural arrangement facilitates a different tunneling pathway that
      leads to a lower effective barrier for magnetization reorientation for compound
      2. The substitution of the acetate ligands by trifluoroacetic acid was monitored
      by mass spectrometry, which is a convenient tool for judging completion of the
      substitution process.

PMID- 14966972
TI  - CS2N3(-)-containing pseudohalide species: an experimental and theoretical study.
AB  - The first structural reports of anhydrous salts containing the CS2N3 moiety are
      presented. The new M(+)CS2N3- species (M = NH4 (1), (CH3)4N (2), Cs (3), K (4))
      were characterized by vibrational spectroscopy (IR, Raman), as well as
      multinuclear NMR spectroscopy (1H, 13C, 14N NMR). Moreover, the solid-state
      structures of NH4CS2N3 (1) [orthorhombic, Pbca, a = 10.6787(1) A, b = 6.8762(1)
      A, c = 15.2174(2) A, V = 1117.40(2) A3, Z = 8] and (H4C)4NCS2N3 (2) [monoclinic,
      P2(1)/m, a = 5.9011(1) A, b = 7.3565(2) A, c = 10.9474(3) A, beta = 91.428(1)
      degrees, V = 475.09(2) A3, Z = 2] were determined using X-ray diffraction
      techniques. The covalent compound CH3CS2N3 (5) was prepared by the reaction of
      methyl iodide with sodium azidodithiocarbonate and was characterized by
      vibrational spectroscopy (IR, Raman), multinuclear NMR spectroscopy (1H, 13C,
      14N), and X-ray diffraction techniques [monoclinic, P2(1)/m, a = 5.544(1) A, b =
      6.4792(7) A, c = 7.629(1) A, beta = 105.53(2) degrees, V = 264.06(7) A3, Z = 2].
      Furthermore, the gas-phase structure of 5 was calculated (MPW1PW91/cc-pVTZ) and
      found to be in very good agreement with the experimentally determined structure.
      Improved synthetic routes for the recently reported dipseudohalogen (CS2N3)2 and
      interpseudohalogen CS2N3CN (6) are described, and the calculated gas-phase
      structure of 6 was compared with the experimentally determined structure (X-ray).
      The vibrational spectra of 6 and HCS2N3 (7) are also reported. Furthermore,
      several plausible isomers for 7 were calculated in an attempt to rationalize the
      experimentally observed structure which has N-H and not S-H connectivity. The
      lowest energy isomer for 7 is in agreement with the experimentally observed
      structure, and the Bronsted acidity was calculated at the MPW1PW91/cc-pVTZ level
      of theory. The unknown CSe2N3- anion (8) was also investigated both theoretically
      and experimentally, and the structure and vibrational data for the unknown CTe2N3
      anion (9) were investigated by quantum-chemical calculations using a quasi
      relativistic pseudopotential for Te (ECP46MWB) and a cc-pVTZ basis set for C and
      N. The gas-phase structure of 9 is predicted to be that of a five-membered ring
      in analogy to the sulfur and selenium analogues.

PMID- 14966973
TI  - [(NH3)5Ru(1,2,4,5-tetrazine)]2+: synthesis and experimental and theoretical study
      of its solvatochromism in the visible spectral region.
AB  - The title compound has been first synthesized and fully characterized as both
      tetraphenylborate and perchlorate salt. Its 300-900 nm absorption spectrum,
      recorded in nitromethane, water, and dimethyl sulfoxide, reveals the peculiar
      existence of two distinct bands whose intensities depend on the solvent donor
      number. This feature can be attributed to two separate metal-to-ligand charge
      transfer transitions, in agreement with the theoretical predictions obtained by
      extensive configuration interaction calculations, which take into account the
      solvent effects. The calculation of the potential energy curves of the ground and
      excited states along the Ru-tetrazine coordinate allows the interpretation of the
      relative intensities of the observed bands, as well as the interpretation of
      their line-shape profiles.

PMID- 14966974
TI  - Axial Ligand exchange in chiral macrocyclic ytterbium(III) complexes.
AB  - We investigate the role of axial ligands on the near-IR-optical and paramagnetic
      NMR spectra of the complex [YbL](+3) where L is the stereodefined enantiopure
      chiral macrocycle (L =
      hexaazapentacyclo[25.3.1.1(12,24).0(4,9).0(19,24)]dotriaconta
      1(31),2,10,12,14,16(32),17,25,27,29-decaene). The conformation in solution of the
      lanthanide complex is characterized by analyzing the pseudocontact 1H NMR shifts
      and is consistent with X-ray data of single crystal of analogue systems. The
      macrocycle is confined within a thin equatorial disk, leaving the cation open to
      at least two axial sites, on the opposite hemispheres. We recorded, assigned, and
      analyzed the 1H NMR spectra of several species upon changing the anion in
      solution, calculating the magnetic susceptibility anisotropy tensor for each.
      Near-IR circular dichroism is used to investigate the solution equilibria
      involving the competing ligands and to derive a spectroscopic series for Yb.

PMID- 14966975
TI  - Kinetics and mechanism of bromate-bromide reaction catalyzed by acetate.
AB  - The initial rate of the bromate-bromide reaction, BrO3- + 5Br- + 6H+ --> 3Br2 +
      3H2O, has been measured at constant ionic strength, I = 3.0 mol L(-1), and at
      several initial concentrations of acetate, bromate, bromide, and perchloric acid.
      The reaction was followed at the Br2/Br3- isosbestic point (lambda = 446 nm) by
      the stopped-flow technique. A very complex behavior was found such that the
      results could be fitted only by a six term rate law, nu = k1[BrO3-][Br-][H+]2 +
      k2[BrO3-][Br-]2[H+]2 + k3[BrO3-][H+]2[acetate]2 + k4[BrO3-][Br-]2[H+]2[acetate] +
      k5[BrO3-][Br-][H+]3[acetate]2 + k6[BrO3-][Br-][H+]2[acetate], where k1 = 4.12 L3
      mol(-3) s(-1), k2 = 0.810 L4 mol(-4) s(-1), k3 = 2.80 x 10(3) L4 mol(-4) s(-1),
      k4 = 278 L5 mol(-5) s(-1), k5 = 5.45 x 10(7) L6 mol(-6) s(-1), and k6 = 850 L4
      mol(-4) s(-1). A mechanism, based on elementary steps, is proposed to explain
      each term of the rate law. This mechanism considers that when acetate binds to
      bromate it facilitates its second protonation.

PMID- 14966976
TI  - Stabilization of new forms of the intermetallic phases beta-RENiGe2 (RE = Dy, Ho,
      Er, Tm, Yb, Lu) in liquid indium.
AB  - Flux conditions using liquid indium bypass the thermodynamically stable structure
      and yield new forms of the phases RENiGe2 (RE = Dy, Er, Yb, Lu). The compounds
      crystallize in the orthorhombic Immm space group and possess the YIrGe2 structure
      type. Lattice parameters for ErNiGe2, DyNiGe2, YbNiGe2, and LuNiGe2 are a =
      4.114(1) A, b = 8.430(2) A, c = 15.741(5) A; a = 4.1784(9) A, b = 8.865(2) A, c =
      15.745(3) A; a = 4.0935(6) A, b = 8.4277(13) A, c = 15.751(2) A, and a = 4.092(1)
      A, b = 8.418(3) A, c = 15.742(5) A, respectively. These phases represent a new
      structural arrangement (beta) of the compound type RENiGe2 as another set of
      compounds with identical stoichiometry are known to adopt the orthorhombic Cmcm
      CeNiSi2 type structure (alpha). In this paper we report the crystal and
      electronic band structure of four new members of the YIrGe2 structure type, as
      well as an investigation of the relative thermodynamic stabilities of the two
      forms.

PMID- 14966977
TI  - Calculation of the ground and excited states of a mixed valence compound
      [Fe2(OH)3(NH3)6]2+: a class II or class III compound?
AB  - The effective group potentials (EGP) approach has been successfully used for the
      computation of the ground and excited states energies of the mixed valence
      compound [Fe2(OH)3(NH3)6]2+. It is the first time that for a system as big as the
      complex presented above the ground and excited states are computed with their own
      orbitals and studied in such a detailed way. First of all, the NH3 EGP was
      validated by comparing calculations where NH3 was treated explicitly at different
      levels of calculations. Once the validation was obtained, the complete spectrum
      of the compound under interest was calculated and compared with results obtained
      in a previous work by Barone et al. and the spin Hamiltonian of widespread use.
      Some deviations from these predictive approaches were observed. This allowed us
      to emphasize the importance of the dynamic correlation which is not included
      explicitly in the spin Hamiltonian. Then, the influence of vibration has been
      studied by computing the potential energy curves obtained when moving the (OH)3
      plane. This study shows that our calculations lead to a delocalized compound
      (class III) as expected according to former experimental data.

PMID- 14966978
TI  - Platinum ion uptake by dendrimers: an NMR and AFM study.
AB  - The reaction of generation 2 and generation 4 poly(amidoamine) (PAMAM) dendrimers
      with K2PtCl2 was studied by several NMR methods. The time dependency of the
      Pt(II) complexation was followed with 195Pt NMR for both dendrimers and the
      equilibrium product was further characterized with (1)H NMR, and indirectly
      detected 13C NMR, in the case of the generation 2 dendrimer. After 2 days, a
      black precipitate of Pt(0) was observed, half the original 195Pt signal was lost,
      and approximately 20% of the initial Pt(II) was coordinated to the tertiary and
      secondary nitrogens of the generation 2 dendrimer. The uptake of Pt(II) by the
      generation 4 dendrimer was much slower, consistent with the steric crowding of
      the surface groups on the generation 4 dendrimer compared to the more open
      generation 2. After 10 days, 80% of the Pt(II) was deep within the generation 4
      dendrimer; the remaining 20% was unreacted or bound near the surface nitrogens of
      a single dendrimer. The location and time course of the platinum ion uptake by
      the dendrimers provides valuable insight into the formation of Pt(0)
      nanoparticles made in the presence of dendrimers as stabilizers, visualized by
      atomic force microscopy.

PMID- 14966979
TI  - Highly localized charges control electrostriction: reaction volumes for the
      reduction of mononuclear and bridged ruthenium complexes.
AB  - Changes in electrostriction caused by the reduction of metal centers in monomeric
      Ru and bridged Ru/Fe complexes reported in this work are highly localized in a
      polar solvent such as water. In mononuclear complexes, such as [(edta
      H)Ru(III)(H2O)], where the pendant carboxylate is protonated or not depending on
      pH, the charge that determines electrostricted solvent behavior is defined within
      distances encompassed by the first coordination sphere of the redox center
      (DeltaV(complex) = 1.4 +/- 0.6 cm3 mol(-1) (pH 4) or 0.9 +/- 0.6 cm3 mol(-1) (pH
      1.1)). Furthermore, in dinuclear complexes, even differences in the ligand charge
      around the second metal center have insignificant effects on electrostrictive
      interaction with the solvent. Reduction of the Fe center in the systems
      [(NH3)5Ru(III)(mu-NC)Fe(III)(CN)5] and [(edta)Ru(III)(mu-NC)Fe(III)(CN)5]4- is
      virtually unaffected (-21.8 +/- 1.8 cm3 mol(-1) and -21.7 +/- 2.8 cm3 mol(-1),
      respectively) when the Ru center is changed from formally cationic (3+) to
      anionic (1-).

PMID- 14966980
TI  - F2Al(mu-eta2:eta2-O2)AlF2: an unusual, stable aluminum peroxo compound.
AB  - The oxidation processes in the industrial production of aluminum from cryolite
      melts are not fully understood. Oxidation of AlOF2- leads initially to AlOF2
      radicals. The structure of the AlOF2 dimer and several oxidized and reduced forms
      of this compound are investigated by theoretical methods and compared to
      analogous boron and gallium compounds. The thermodynamic stability of these
      compounds is investigated. It is shown that the dimeric compound of AlOF2
      contains a symmetric peroxo bridge and is unexpectedly stable toward
      decomposition.

PMID- 14966981
TI  - Correlation between the magnetic g tensors and the local cysteine geometries for
      a series of reduced [2Fe-2S*] protein clusters. A quantum chemical density
      functional theory and structural analysis.
AB  - We relied on the density functional theory (DFT) to study the electronic
      structure of the [2Fe-2S*](SH)4 model of the active site of 2Fe ferredoxins and
      other proteins containing reduced [2Fe-2S*] clusters. The two (Fe(3+)-Fe(2+)-S-H)
      dihedral angles Omega1 and Omega2 defined for the two ligands on the ferrous side
      were allowed to vary, while the two other (Fe(2+)-Fe(3+)-S-H) angles Omega3 and
      Omega4 on the ferric side were kept constant. The Lande (g), magnetic hyperfine,
      and quadrupole tensors for two geometries, C2 (Omega1 = Omega2) and Cs (Omega1 = 
      Omega2), were calculated. To apply our model to the actual proteins, we listed
      all of the crystallographic structures available for the [2Fe-2S*] systems. A
      classification of these proteins, based on the four dihedral angles
      [Omega(i)](i=1-4), separates them into three main classes. The main structural
      feature of the first class (Omega1 approximately Omega2), with an average
      dihedral angle Omega(av) = (Omega1 + Omega2)/2 comprised between 115 degrees and
      150 degrees, corresponds to a local ferrous C2 geometry (rather than C2nu, as
      previously assumed by Bertrand and Gayda: Biochim. Biophys. Acta 1979, 579, 107).
      We then established a direct correlation between the three principal g values and
      Omega(av). It is the first time that such a link has been made between the
      spectroscopic and structural parameters, a link, moreover, fully rationalized by
      our DFT calculations. We finally point out the basic differences between our C2
      results with those of the C2nu phenomenological model proposed in the late 1970s
      by Bertrand and Gayda.

PMID- 14966982
TI  - New coordination compounds of Cd(AsF6)2 with HF and XeF2.
AB  - Two new coordination compounds of cadmium with HF and XeF2 as ligands have been
      synthesized. Solid white [Cd(HF)](AsF6)2 is obtained from an anhydrous HF (aHF)
      solution of Cd(AsF6)2. It crystallizes in a monoclinic P2(1)/c space group with a
      = 9.4687(14) A, b = 9.2724(11) A, c = 10.5503(18) A, beta = 104.887(7) degrees,
      and Z = 4. The coordination sphere of Cd consists of 7 + 2 fluorine atoms, which
      are in a capped trigonal-prismatic arrangement. The reaction between Cd(AsF6)2
      and XeF(2 in aHF yields a solid white product at room temperature having the
      composition [Cd(XeF2)4](AsF6)2 after the excess XeF2 and solvent have been
      removed under dynamic vacuum. [Cd(XeF2)4](AsF6)2 crystallizes in the orthorhombic
      space group P2(1)2(1)2(1), with a = 8.6482(6) A, b = 13.5555(11) A, c =
      16.6312(14) A, and Z = 4. The coordination sphere of Cd consists of eight
      fluorine atoms, which are at the corners of a trigonal prism with two capped side
      faces.

PMID- 14966983
TI  - 1-ethyl-3-methylimidazolium based ionic liquids containing cyano groups:
      synthesis, characterization, and crystal structure.
AB  - New 1-ethyl-3-methylimidazolium (EMI) salts [EMI][C(CN)3] and [EMI][Ag(CN)2] were
      prepared and characterized. The C(CN)3 salt has a melting point at -11 degrees C
      and shows a low viscosity (18 cP) and a high ionic conductivity (1.8 x 10(-2) S
      cm(-1)) at room temperature. This conductivity is less than that of [EMI][N(CN)2]
      salt (2.7 x 10(-2) S cm(-1)), possibly due to the larger molecular weight of the
      anion. The first EMI salt containing Ag(I) complexes [EMI][Ag(CN)2] has a higher
      melting point of 73 degrees C. In the crystal, the C-H...pi interionic
      interactions between cations construct zigzag chains in the cationic two
      dimensional layer. Close Ag..Ag interionic contacts of 3.226(1) A were observed
      in the one-dimensional anionic chain, and the relatively high melting point among
      the EMI salts with a monoanion appears to be governed essentially by these direct
      Ag...Ag interactions.

PMID- 14966984
TI  - Oxidative self-decomposition of the nickel(III) complex of glycylglycyl-L
      histidylglycine.
AB  - Self-decomposition of the nickel(III) doubly deprotonated peptide complex of
      Gly2HisGly occurs by base-assisted oxidation of the peptide. At < or =p[H+] 7.0,
      the major pathway is a four-electron oxidation (via 4 Ni(III) complexes) at the
      alpha carbon of the N-terminal glycyl residue. The product of this oxidation is
      oxamylglycylhistidylglycine, which hydrolyzes to yield ammonia and
      oxalylglycylhistidylglycine. Both of these peptide products decompose to give
      isocyanatoacetylhistidylglycine. A small amount (2%) of oxidative decarboxylation
      also is observed. In another major pathway above p[H+] 7.0, two Ni(III)-peptide
      complexes coordinate via an oxo bridge in the axial positions to form a reactive
      dimer species. This dimer generates two Ni(II)-peptide radical intermediates that
      cross-link at the alpha carbons of the N-terminal glycyl residues. In 0.13 mM
      Ni(III)-peptide at p[H+] 10.3, this pathway accounts for 60% of the reaction. The
      cross-linked peptide is subject to oxidation via atmospheric O2, where the 2,3
      diaminobutanedioic acid is converted to a 2,3-diaminobutenedioic acid. The
      products observed at <p[H+] 7.0 are observed here as well, although in lower
      yields. The reactivity of Ni(III)(H(-2)Gly2HisGly) is significantly different
      than that of Cu(III)(H(-2)Gly2HisGly), which undergoes a two-electron oxidation
      at the histidyl residue with no peptide-peptide cross-linking in basic solution.

PMID- 14966985
TI  - A geometrically constraining bis(benzimidazole) ligand and its nearly tetrahedral
      complexes with Fe(II) and Mn(II).
AB  - 2,2'-Bis[2-(1-propylbenzimidazol-2-yl)]biphenyl), 4, and its bis complexes with
      Fe(II) and Mn(II) have been prepared and characterized structurally and
      spectroscopically. Ligand 4 adopts an open, "trans" conformation in the solid
      state with the benzimidazole (BzIm) groups on opposite sides of the biphenyl
      unit. In its complexes with metal ions, a "cis" conformation is observed, and 4
      behaves as a geometrically constraining bidentate ligand with four planar groups
      connected by three "hinges". Reaction of 4 with Fe(II) or Mn(II) yielded
      isomorphous crystals (space group Pnn2) of Fe(II)(4)2.(ClO4)2 and
      Mn(II)(4)2.(ClO4)2, in which the M(II)(4)2 cations exhibit distorted-tetrahedral
      coordination geometries (N-M-N angles, 109 +/- 11 degrees ) enforced by rigid,
      chiral nine-membered M(4) rings in the twist-boat-boat conformation.
      Individually, the cations show R,R or S,S stereochemistry, and the crystals are
      racemates. Mn(II)(4)2.(ClO4)2 exhibits a quasi-reversible Mn(II) --> Mn(III)
      oxidation at E(1/2) = 0.64 V; the corresponding Fe(II) --> Fe(III) oxidation
      occurs at E(1/2) = 1.76 V. The electrochemical stability of the Fe(III) oxidation
      state in this system suggests the possibility of isolating an unusual
      pseudotetrahedral Fe(III)N(BzIm)(4) species. Ultraviolet spectra of the iron and
      manganese complexes are dominated by absorptions of the ligand 4 blue-shifted by
      approximately 2000-3000 cm(-1). Ligand-field absorptions were observed for the
      Fe(II) complex; those for the Mn(II) complex were obscured by tailing ultraviolet
      absorptions. Electron paramagnetic resonance and magnetic susceptibility
      measurements are consistent with a high-spin Mn(II) complex, while for the Fe(II)
      complex, the falloff of the magnetic moment with decreasing temperature is
      indicative of zero-field splitting with D approximately 4 cm(-1).

PMID- 14966986
TI  - Syntheses, structures, and redox properties of dimeric triruthenium clusters
      bridged by bis(diphenylphosphino)acetylene and -ethylene.
AB  - Reactions of oxo-centered triruthenium acetate complexes
      [Ru3O(OAc)6(py)2(CH3OH)](PF6) (py = pyridine, OAc = CH3COO-) (1) with nearly
      equimolar amounts of dppa [bis(diphenylphosphino)acetylene] or dppen [trans-1,2
      bis(diphenylphosphino)ethylene] gave [Ru3O(OAc)6(py)2(L)](PF6) (L = dppa, 2;
      dppen, 3). With 2.4 equiv of 1, the reactions provided diphosphine-linked
      triruthenium dimers, [[Ru3O(OAc)6(py)2]2(L)](PF6)2 (L = dppa, 4; L = dppen, 5),
      respectively. Similarly, the reactions of [Ru3O(OAc)6(L')2(MeOH)]+ [L' = dmap (4
      (dimethylamino)pyridine), 1a; L' = abco (1-azabicyclo[2.2.2]octane), 1b] with
      dppen gave dppen-linked dimers, [[Ru3O(OAc)6(dmap)2]2(dppen)](SbF6)2 (6) and
      [[Ru3O(OAc)6(abco)2]2(dppen)](BF4)2 (7), respectively. The chemical reduction of
      2, 4, and 5 by hydrazine afforded one- or two-electron-reduced, neutral products,
      Ru3O(OAc)6(py)2(dppa) (2a), [Ru3O(OAc)6(py)2]2(dppa) (4a), and
      [Ru3O(OAc)6(py)2]2(dppen) (5a), respectively. The complexes were characterized by
      elemental analyses, ES-MS, UV-vis, IR, and 31P NMR spectroscopies, and cyclic and
      differential-pulse voltammetries. The molecular structures of compounds 2, 4, 5,
      5a, 6, and 7 were determined by single-crystal X-ray diffraction. In 0.1 M
      (Bu4N)PF6-acetone, the monomers and dimers of triruthenium clusters show
      reversible and multistep redox responses. The two triruthenium cluster centers in
      dimers undergo stepwise reductions and oxidations due to the identical redox
      processes of the individual Ru3O cluster cores, suggesting the presence of
      electronic communications between them through the conjugated diphosphine spacer.
      The redox wave splitting mediated by dppa containing an ethynyl group (C triple
      bond C) is found to be more extensive than that by dppen containing an ethenyl
      (C=C) one. It appears that the redox wave splitting is enhanced by the
      introduction of electron-donating substituents on the auxiliary pyridine rings.

PMID- 14966987
TI  - Organometallic oligomers based on 1,8-Diisocyano-p-menthane (dmb): syntheses and
      characterization of the [[M(diphos)(dmb)]BF4]n and [[Pd2(diphos)2(dmb)](ClO4)2]n
      materials (M = Cu, Ag; diphos = dppe, dppp).
AB  - A new strategy to synthesize organometallic oligomers is presented and consists
      of using the title diisocyanide and chelated metal fragments with
      bis(diphenylphosphine)alkanes. The title materials are synthesized by reacting
      the [M(dppe)(BF4)] and [M2(dppp)2](BF4)2 complexes (M = Cu, Ag; dppe =
      bis(diphenylphosphino)ethane, dppp = bis(diphenylphosphino)propane) with dmb and
      the Pd2-bonded d9-d9 Pd2(dmb)2Cl2 dimer with dppe or dppp. The model compounds
      [M(diphos)(CN-t-Bu)2]BF4 (M = Cu, Ag) and [Pd2(diphos)2(CN-t-Bu)2](ClO4)2 (diphos
      = dppe, dppp) have been prepared and characterized as well for comparison
      purposes. Three of the model compounds were also characterized by X-ray
      crystallography to establish the diphosphine chelating behavior. The materials
      are amorphous and have been characterized from the measurements of the intrinsic
      viscosity, DSC, TGA, and XRD, as well as their capacity for making stand-alone
      films. The intrinsic viscosity data indicate that the Cu and Pd2 materials are
      oligomeric in solution (approximately 8-9 units), while the Ag materials are
      smaller. For [[Cu(dppe)(dmb)]BF4]n, a glass transition is reproducibly observed
      at about 82 degrees C (DeltaCp = 0.43 J/(g deg)), which suggests that these
      materials are polymeric in the solid state. The Cu and Ag species are luminescent
      in the solid state at room temperature exhibiting lambda(max) and tau(e)
      (emission lifetime) around 480-550 nm and 18-48 micros, respectively, while the
      Pd2 species are not luminescent under these conditions. During the course of this
      study, the unsaturated [M2(dppp)2](BF4)2 starting materials (M = Cu, Ag) were
      prepared, one of which (M = Ag) was characterized by crystallography. The
      bridging behavior of the dppp ligand in this case contrasts with the chelating
      behavior seen for the saturated [Cu(dppp)(CN-t-Bu)2]BF4 complex.

PMID- 14966988
TI  - Paramagnetic 1H NMR spectrum of the cobalt(II) derivative of spinach
      plastocyanin.
AB  - The native type 1 copper ion of spinach plastocyanin has been substituted with
      Co(II). The UV/vis spectrum of this derivative is similar to those for other
      Co(II)-substituted cupredoxins. The paramagnetic 1H NMR spectrum of Co(II)
      plastocyanin has been completely assigned. A number of similar studies on Co(II)
      cupredoxins have been published, but this is the first such analysis of a
      substituted plastocyanin that possesses the archetypal type 1 active site. A
      truly representative comparison of the available paramagnetic 1H NMR data for
      Co(II) cupredoxins is now possible. We demonstrate in this work that there is
      very little difference in the metal-ligand contacts between the Co(II)
      derivatives of cupredoxins possessing a type 1 axial site (plastocyanin) and
      those having perturbed (rhombic) spectroscopic features.

PMID- 14966989
TI  - Steric control of coordination number: A series of Mo(VI) dioxo diaryloxide
      complexes bearing 4-, 5-, and 6-coordinate environments.
AB  - The design, synthesis, and structure determination of a series of Mo(VI) dioxo
      diaryloxide complexes have been reported. By varying the steric bulk of the
      aryloxide ligand, control of the coordination number around the Mo(VI) center was
      achieved. All the complexes are characterized by analytical and spectroscopic
      techniques. Preliminary reactivity tests indicate that the 4-coordinate compound
      is the most stable and the 6-coordinate compound is the least stable.

PMID- 14966990
TI  - The solution structure of rhombic lanthanide complexes analyzed with a Model-free
      and crystal-field independent paramagnetic NMR method: application to nonaxial
      trimetallic complexes [LnxLu(3-x)(TACI-3H)2(H2O)6]3+ (x = 1-3).
AB  - The model-free approach has been extended with the derivation of a novel three
      nuclei crystal-field independent method for investigating isostructurality in
      nonaxial (i.e., rhombic) complexes along the lanthanide series. Application of
      this technique to the heterotrimetallic sandwich complexes [LnLu2(TACI
      3H)2(H2O)6]3+, which possess a single C2v-symmetrical paramagnetic center,
      unambiguously evidences isostructurality for Ln = Pr-Yb, while the variation of
      the second-rank crystal-field parameters and along the series prevents reliable
      structural analyses with the classical one-nucleus equation. Extension toward
      polymetallic magnetically noncoupled rhombic lanthanide complexes in [Ln2Lu(TACI
      3H)2(H2O)6]3+ (two paramagnetic centers with Cs microsymmetry) and [Ln3(TACI
      3H)2(H2O)6]3+ (three paramagnetic centers with C2v microsymmetry) requires only
      minor modifications of the original three-nuclei equation. Isostructurality
      characterizes [Ln2Lu(TACI-3H)2(H2O)6]3+ (Ln = Pr-Yb), while [Ln3(TACI
      3H)2(H2O)6]3+ exhibit a structural change between Eu and Tb which results from
      the concomitant contraction of the three metallic centers. Particular attention
      has been focused on (i) the stepwise increase of contact (i.e., through-bond) and
      pseudocontact (i.e., through-space) contributions when the number of paramagnetic
      centers increases, (ii) the assignment of 13C resonances in the strongly
      paramagnetic complexes [Ln3(TACI-3H)2(H2O)6]3+ (Ln = Tb-Yb) for which reliable T1
      measurements and [1H-13C] correlation spectra are not accessible, and (iii) the
      combination of crystal-field dependent and independent methods for analyzing the
      paramagnetic NMR spectra of axial and nonaxial lanthanide complexes.

PMID- 14966991
TI  - Metal vs ligand reduction in complexes of dipyrido[3,2-a:2',3'-c]phenazine and
      related ligands with [(C5Me5)ClM]+ (M = Rh or Ir): evidence for potential rather
      than orbital control in the reductive cleavage of the metal-chloride bond.
AB  - Complexes between the chlorometal(III) cations [(C5Me5)ClM]+, M = Rh or Ir, and
      the 1,10-phenanthroline-derived alpha-diimine (N--N) ligands dipyrido[3,2-a:2',3'
      c]phenazine (dppz), 1,4,7,10-tetraazaphenanthrene (tap), or 1,10-phenanthroline
      5,6-dione (pdo) were investigated by cyclic voltammetry, EPR, and UV-vis-NIR
      spectroelectrochemistry with respect to either ligand-based or metal-centered
      (and then chloride-dissociative) reduction. Two low-lying unoccupied molecular
      orbitals (MOs) are present in each of these three N wedge N ligands; however,
      their different energies and interface properties are responsible for different
      results. Metal-centered chloride-releasing reduction was observed for complexes
      of the DNA-intercalation ligands dppz and tap to yield compounds [(N--N)(C5Me5)M]
      in a two-electron step. The separation of alpha-diimine centered optical orbitals
      and phenazine-based redox orbitals is apparent from the EPR and UV-vis-NIR
      spectroelectrochemistry of [(dppz)(C5Me5)M](0/*-/2-). In contrast, the pdo
      complexes undergo a reversible one-electron reduction to yield o-semiquinone
      radical complexes [(pdo)(C5Me5)ClM]* before releasing the chloride after the
      second electron uptake. The fact that the dppz complexes undergo a Cl(-)
      dissociative two-electron reduction despite the presence of a lowest lying pi* MO
      (b1(phz)) with very little overlap to the metal suggests that an unoccupied
      metal/chloride-based orbital is lower in energy. This assertion is confirmed both
      by the half-wave reduction potentials of the ligands (tap, -1.95 V; dppz, -1.60
      V; pdo, -0.85 V) and by the typical reduction peak potentials of the complexes
      [(L)(C5Me5)ClM](PF6) (tap, -1.1 V; dppz, -1.3 V; pdo, -0.6 V; all values against
      Fc(+/0)).

PMID- 14966992
TI  - Synthesis, crystal structure, and spectroscopic characterization of trans-bis[(mu
      1,3-bis(4-pyridyl)propane)(mu-(3-thiopheneacetate-O))(3-thiopheneacetate
      O)]dicopper(II), [[Cu2(O2CCH2C4H3S)4mu-(BPP)2]]n: from a dinuclear paddle-wheel
      copper(II) unit to a 2-D coordination polymer involving monatomic carboxylate
      bridges.
AB  - From the reaction between a dinuclear paddle-wheel carboxylate, namely [Cu2mu
      (O2CCH2C4H3S)4] (1), and the flexible ligand 1,3-bis(4-pyridyl)propane (BPP) a
      neutral 2-D coordination polymer [[Cu2(O2CCH2C4H3S)4mu-(BPP)2]]n (2) was
      obtained. Compounds 1 and 2 were characterized by means of elemental analysis,
      thermal analysis (TG/DSC), vibrational spectroscopy, and electron paramagnetic
      resonance (EPR). The crystal structure of 2 reveals that each Cu(II) is
      coordinated by two nitrogen atoms from different BPP ligands and two 3
      thiopheneacetate groups within a distorted square planar geometry in a trans-[N,
      N, O, O] arrangement. The BPP ligand adopts a TG conformation bridging two copper
      centers giving rise to a 1-D sinusoidal polymeric chain along the
      crystallographic c axis. Adjacent 1-D chains are extended into a 2-D coordination
      network through pairs of monatomic carboxylate bridges in direction of the b
      axis. This bridging mode affords centrosymmetric dimeric units Cu2O2, and
      therefore, the copper ions are involved in a CuN2O2O' chromophore displaying a (4
      + 1) square pyramidal coordination in the resultant 2-D polymeric network. The
      polycrystalline X-band EPR spectrum of 2 at room temperature is characteristic of
      a triplet state with nonnegligible zero-field splitting in agreement with the
      crystal structure. Crystal data for 2: monoclinic, space group P2(1)/c, a =
      9.4253(10) A, b = 10.9373(10) A, c = 23.6378(10) A, beta = 98.733(4) degrees, Z =
      2.

PMID- 14966993
TI  - Easy preparation of the tris(2-fluoro-6-pyridylmethyl)amine ligand and
      instantaneous reaction of the corresponding dichloroferrous complex with
      molecular dioxygen: new access to dinuclear species.
AB  - The tris(2-fluoro-6-pyridylmethyl)amine ligand, F3TPA, can easily be prepared by
      reaction of 2-fluoro-6-bromomethylpyridine with NH4Cl in the presence of NaOH.
      Complexation to FeCl2 affords the high-spin F3TPAFe(II)Cl2 complex, the X-ray
      structure of which is reported. The three fluorine substituents provide enough
      steric hindrance to force the tripod to coordinate in the tridentate mode,
      affording a trigonal bipyramidal iron center. This complex is thermally stable,
      and it reacts instantaneously with molecular dioxygen to afford the unsymmetrical
      micro-oxo dimer F3TPAFe(III)ClOFe(III)Cl3 as the major product, together with
      small amounts of the mixed salt [F3TPAFe(II)Cl]2, [Fe(III)2OCl6]. These two
      complexes have been isolated and characterized by X-ray diffraction analysis. A
      mechanism by which they are obtained is suggested and seems to parallel the well
      known process of autoxidation of ferrous porphyrins.

PMID- 14966994
TI  - Contrasting intrastrand photoinduced processes in macromolecules containing
      pendant -Re(CO)3(1,10-phenanthroline)+: electron versus energy transfer.
AB  - The photochemical and photophysical properties of the polymers [(vpy-CH3+)2
      vpyRe(CO)3(phen)+]200 (vpy = vinyl pyridine, phen = 1,10-phenanthroline) have
      been investigated in solution phase and compared to those of a related polymer,
      [(vpy)2-vpyRe(CO)3(phen)+]200, and monomer, pyRe(CO)3(phen)+. Irradiations at 350
      nm induce intrastrand charge separation in the peralkylated polymer, a process
      that stands in contrast with the energy migration observed with [(vpy)(2)
      vpyRe(CO)3(phen)+]200. Electronically excited -vpyRe(CO)3(phen)+ chromophores and
      charge-separated intermediates react with neutral species, e.g., 2,2',2' '
      nitrilotriethanol, and anionic electron donors, e.g., SO3(2-) and I-. The anionic
      electron donors react more efficiently with the metal-to-ligand charge transfer
      excited state of these polyelectrolytes than with the excited state of
      pyRe(CO)3(phen)+.

PMID- 14966995
TI  - Tetranuclear [Rh4(mu-PyS2)2(diolefin)4] complexes as building blocks for new
      inorganic architectures: synthesis of coordination polymers and heteropolynuclear
      complexes with electrophilic d8 and d10 metal fragments.
AB  - The reaction of [Rh4(mu-PyS2)2(cod)4] (PyS2 = 2,6-pyridinedithiolate, cod = 1,5
      cyclooctadiene) with CF3SO3Me gave the cationic complex [Rh(4)(mu
      PyS(2)Me)(2)(cod)4][CF3SO3]2 (1) with two 6-(thiomethyl)pyridine-2-thiolate
      bridging ligands from the attack of Me+ at the terminal sulfur atoms of the
      starting material. Under identical conditions [Rh4(mu-PyS2)2(tfbb)4] (tfbb =
      tetrafluorobenzobarrelene) reacted with CF3SO3Me to give the mixed-ligand complex
      [Rh(4)(mu-PyS2)(mu-PyS2Me)(tfbb)4][CF3SO3] 2. The nucleophilicity of the bridging
      ligands in the complexes [Rh4(mu-PyS2)2(diolefin)4] was exploited to prepare
      heteropolynuclear species. Reactions with [Au(PPh3)(Me2CO)][ClO4] gave the
      hexanuclear complexes [(PPh3)2Au2Rh4(mu-PyS2)2(diolefin)4][ClO4]2 (diolefin = cod
      (3), tfbb (4)). The structure of 4, solved by X-ray diffraction methods, showed
      the coordination of the [Au(PPh3)]+ fragments to the peripheral sulfur atoms in
      [Rh4(mu-PyS2)2(diolefin)4] along with their interaction with the neighbor rhodium
      atoms. Neutral coordination polymers of formula [ClMRh4(mu-PyS2)2(diolefin)4]n (M
      = Cu (5, 6), Au (7)) result from the self-assembly of alternating [Rh4(mu
      PyS2)2(diolefin)4] ([Rh4]) blocks and MCl linkers. The formation of the infinite
      polymetallic chains was found to be chiroselective for M = Cu; one particular
      chain contains exclusively homochiral [Rh4] complexes. Cationic heterometallic
      coordination polymers of formula [MRh4(mu-PyS2)2(diolefin)4]n[BF4]n (M = Ag (8,
      9), Cu (10, 11)) and [Rh5(mu-PyS2)2(diolefin)5]n[BF4]n (12, 13) result from the
      reactions of [Rh4] with [Cu(CH2CN)4]BF4, AgBF4, and [Rh(diolefin)(Me2CO)2]BF4,
      respectively. The heterometallic coordination polymers exhibit a weak electric
      conductivity in the solid state in the range (1.2-2.8) x 10(-7) S cm(-1).

PMID- 14966996
TI  - Synthesis and characterization of neutral cis-hexacoordinate bis(beta-diketonate)
      silicon(IV) complexes.
AB  - Three new neutral cis-hexacoordinate bis(beta-diketonato) silicon(IV) complexes,
      (thd)2SiX2, where X = Me (1), tBuO (2), and tAmO (3), and thd = 2,2,6,6
      tetramethyl-3,5-heptanedionato, were synthesized in high yield. Single crystal X
      ray crystallographic analysis revealed that 1 was monomeric with cis
      hexacoordinate octahedral geometry on the silicon and oxygen atoms. Crystal data:
      empirical formula C24H46O4Si, crystal system monoclinic; space group P2(1)/n;
      unit cell dimensions a = 10.4195(5) A, b = 19.7297(10) A, c = 13.6496(7) A; beta
      = 102.6590(10) degrees; Z = 4. Variable temperature NMR confirmed (thd)2SiX2
      maintained cis-geometry in solution by observing two distinct methyl proton
      resonances (of thd) at room temperature or low temperatures. These compounds show
      potential for use as low temperature silicon oxide CVD precursors for transition
      metal silicate high kappa gate dielectrics.

PMID- 14966997
TI  - New poly-iron(II) complexes of N4O dinucleating Schiff bases and pseudohalides:
      syntheses, structures, and magnetic and Mossbauer properties.
AB  - Six dinuclear ferrous complexes including [Fe2(acpypentO)(O2CMe)(NCS)2] (1),
      [Fe2(acpypentO)(O2CMe)(NCSe)2] (2), [Fe2(acpypentO)(NCO)3] (3),
      ([Fe2(acpybutO)(O2CMe)(NCS)2] (5), [Fe2(acpybutO)(O2CMe)(NCO)2] (6), and
      [Fe2(acpybutO)(O2CMe)(N3)2] (7), one tetranuclear (bis-dinuclear) ferrous
      compound, [Fe4(acpypentO)2(N3)6] (4), and one mononuclear ferrous compound,
      [Fe(acpybutOH)(NCS)2] (8), have been prepared, and their structures and magnetic
      and Mossbauer properties have been studied (acpybutOH = 1,4-bis[[2-pyridyl(1
      ethyl]imino)]butane-2-ol and acpypentOH = 1,5-bis[[2-pyridyl(1
      ethyl]imino)]pentane-3-ol). The X-ray diffraction analyses yielded the following
      results: 1 (C23H26Fe2N6O3S2, monoclinic, P2(1)/n, a = 8.0380(7) A, b = 12.4495(8)
      A, c = 27.358(2) A, beta = 92.180(10) degrees, V = 2735.7(4) A(3), Z = 4) is a
      dinuclear species in which the unequivalent high-spin (HS) Fe(II) sites are
      bridged by the alkoxo oxygen atom of the symmetrical acpypentO- Schiff base and
      one syn-syn acetato anion; 3 (C22H23Fe2N7O4, triclinic, Ponemacr;, a = 8.4152(10)
      A, b = 9.1350(10) A, c = 17.666(2) A, alpha = 97.486(14) degrees, beta =
      100.026(14) degrees, gamma = 113.510(13) degrees, V = 1195.9(2) A3, Z = 2) is a
      dinuclear species in which the unequivalent HS Fe(II) sites are bridged by the
      alkoxo oxygen atom of the symmetrical acpypentO- Schiff base and one end-on NCO
      anion; 4-MeOH (C39H50Fe4N26O3, triclinic, Ponemacr;, a = 9.1246(11) A, b =
      10.2466(11) A, c = 14.928(2) A, alpha = 91.529(15) degrees, beta = 101.078(16)
      degrees, gamma = 106.341(14) degrees, V = 1309.6(3) A3, Z = 1) is a bis-dinuclear
      species in which the unequivalent HS Fe(II) sites are bridged by the alkoxo
      oxygen atom of the symmetrical acpypentO- Schiff base and one end-on N(3)(-)
      anion, and the symmetry related Fe(II) sites are bridged by two end-on N3-
      anions; 8-MeOH (C21H26FeN6O2S2, triclinic, Ponemacr;, a = 8.7674(9) A, b =
      12.0938(13) A, c = 12.2634(14) A, alpha = 106.685(14) degrees, beta = 93.689(14)
      degrees, gamma = 108.508(13) degrees, V = 1163.7(2) A3, Z = 2) is a mononuclear
      species in which the octahedral low-spin (LS) Fe(II) site is in an N6 environment
      provided by the four N atoms of the protonated asymmetrical acpybutOH Schiff base
      and two thiocyanato anions. The Mossbauer spectra of all dinuclear species (1-3
      and 5-7), and of the bis-dinuclear compound 4, evidence two distinct HS Fe(II)
      sites while the Mossbauer spectra of the mononuclear compound 8 evidence a LS
      Fe(II) site over the 80-300 K temperature range. The temperature dependence of
      the magnetic susceptibility was fitted with J = -13.7 cm(-1), D = -1.8 cm(-1),
      and g = 2.096 for 1; J = 3.0 cm(-1), D(1) = 1.6 cm(-1), E(1) = -0.35 cm(-1)
      (lambda(1) = 0.22), D2 = - 12.2 cm(-1), E2 = 1.1 cm(-1) (lambda2 = 0.09), and g =
      2.136 for 3; and J(1) = - 0.09 cm(-1), J(2) = 15.9 cm(-1), D(1) = 5.7 cm(-1),
      D(2) = 12.1 cm(-1), and g = 1.915 for 4. The nature of the ground state in 3 and
      4 was confirmed by simulation of the magnetization curves at 2 and 5 K. The
      intradinuclear interaction through the central O(alkoxo) of the acpypentO- ligand
      and one pseudohalide bridges is ferromagnetic in 3 (end-on cyanato) while it is
      very weakly antiferromagnetic in 4 (end-on azido). The interdinuclear interaction
      through two end-on azido bridges (4) is ferromagnetic as expected. In agreement
      with the symmetry of the two iron sites of complexes 3 and 4, the fits show that
      D2 (tetragonal pyramid) is larger than D1 (distorted trigonal bipyramid (3) or
      distorted octahedron (4)).

PMID- 14966998
TI  - Cumene oxidation by cis-[RuIV(bpy)2(py)(O)]2+, revisited.
AB  - cis-[RuIV(bpy)2(py)(O)]2+ oxidizes cumene (2-phenylpropane) in acetonitrile
      solution primarily to cumyl alcohol (2-phenyl-2-propanol), alpha-methylstyrene,
      and acetophenone. Contrary to a prior report, the rate of the reaction is not
      accelerated by added nucleophiles. There is thus no evidence for the hydride
      transfer mechanism originally proposed. Instead, the results are consistent with
      a mechanism of initial hydrogen atom transfer from cumene to the ruthenium oxo
      group. This is indicated by the correlation of rate with C-H bond strength and by
      the various products observed. The formation of acetophenone, with one carbon
      less than cumene, is suggested to occur via a multistep pathway involving
      decarbonylation of the acyl radical from 2-phenylpropanal. An alternative
      mechanism involving beta-scission of cumyloxyl radical is deemed unlikely because
      of the difficulty of generating alkoxyl radicals under anaerobic conditions and
      the lack of rearranged products in the oxidation of triphenylmethane by cis
      [RuIV(bpy)2(py)(O)]2+.

PMID- 14966999
TI  - Structural characterization of the major DNA-DNA cross-link of 1,2,3,4
      diepoxybutane.
AB  - 1,2,3,4-Diepoxybutane (DEB) is a bifunctional alkylating agent that exhibits both
      cytotoxic and promutagenic properties. DEB is the ultimate carcinogenic species
      of the major industrial chemical 1,3-butadiene (BD), as well as the active form
      of the antitumor prodrug treosulfan. DEB is tumorigenic in laboratory animals and
      is capable of inducing a variety of genotoxic outcomes, including point
      mutations, large deletions, and chromosomal aberrations. These potent biological
      effects are thought to result from the ability of DEB to form DNA-DNA cross-links
      by consecutive alkylation of two nucleobases within a DNA duplex. Earlier studies
      have provided evidence for the formation of interstrand DNA-DEB lesions involving
      guanine nucleobases, but the covalent structure of DEB-induced DNA cross-link has
      not been previously elucidated. In the present work, the major DNA-DNA cross-link
      of DEB has been identified as 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD).
      The DNA-derived N7-N7 guanine DEB cross-link was characterized by comparing its
      mass spectra, UV spectra, and chromatographic properties to an authentic standard
      prepared by an independent synthesis. Calf thymus DNA treated with relatively low
      concentrations of DEB (5-50 microM) contained similar numbers of bis-N7G-BD and
      the corresponding monoadducts (N7-trihydroxybutyl-guanine), while higher DEB
      exposures produced predominantly monoalkylated lesions. Although both lesions
      spontaneously depurinate at physiological conditions giving rise to abasic sites
      in DNA, bis-N7G-BD lesions have a longer half-life in double-stranded DNA than
      the N7-guanine monoadducts. These studies provide the first rigorous
      characterization of the covalent structure and hydrolytic stability of the major
      DEB-induced DNA-DNA cross-link.

PMID- 14967000
TI  - In vitro metabolism of 2-acetylbenzothiophene: relevance to zileuton
      hepatotoxicity.
AB  - Zileuton, an inhibitor of 5-lipooxygenase, the initial enzyme in the leukotriene
      pathway, was marketed as a new treatment for asthma. This drug has been
      associated with liver toxicity, which has limited its clinical usefulness. We
      provide evidence here that the liver toxicity likely involves a sequence of
      biotransformations leading to 2-acetylbenzothiophene (2-ABT), which is
      subsequently metabolized to give a reactive intermediate(s). In vitro experiments
      with the human lymphoblast MCL5 cell line demonstrated that 2-ABT is cytotoxic in
      a P450-dependent manner. Human liver microsome (HLM) incubations with 2-ABT
      revealed the formation of two short-lived oxidized species, "M + 16" and "M +
      32". Both of these metabolites formed adducts in the presence of GSH or NAC.
      Singly oxidized M + 16 adducts, from either GSH or NAC, appeared to be unstable
      in acidic medium and eliminated water readily to form a new compound. Authentic
      synthetic standards demonstrated that 2-ABT-S-oxide M1 corresponded to the M + 16
      metabolite and that the S-oxide underwent nucleophilic addition with GSH and NAC
      to produce the singly oxidized adducts observed in HLM. The S-oxide adducts
      readily eliminated water to form a rearomatized 2-ABT-GSH adduct or 2-ABT-NAC
      adduct. Coelution experiments with the synthetic standard confirmed the structure
      of the eliminated 2-ABT-NAC adduct C1. LC/MS analyses of urine samples collected
      from rats dosed with zileuton indicate that C1 is a metabolite of zileuton formed
      in vivo. The in vitro and in vivo data presented here demonstrate the formation
      of 2-ABT from zileuton and its further bioactivation to a potentially toxic
      metabolite.

PMID- 14967001
TI  - A novel synthesis of malondialdehyde adducts of deoxyguanosine, deoxyadenosine,
      and deoxycytidine.
AB  - Malondialdehyde (MDA) is a mutagenic product of lipid peroxidation and
      prostaglandin biosynthesis. MDA reacts with DNA bases to produce adducts of
      deoxyguanosine (M1G), deoxyadenosine (M1A), and deoxycytidine (M1C). A novel
      synthesis of these MDA nucleoside adducts has been developed, which significantly
      improves their availability. For the deoxyguanosine adduct, M1G, an amine
      equivalent to MDA, 4-amino-3-(phenylselenyl)butane-1,2-diol, was reacted with 2
      fluoro-O6-(2-(trimethylsilyl)ethyl)-2'-deoxyinosine via a nucleophilic aromatic
      substitution reaction followed by acid hydrolysis of the O6-protecting group to
      give an N2-modified deoxyguanosine intermediate. Periodate oxidation of this
      intermediate under slightly acidic conditions gave M1G in good overall yield via
      cleavage of the vicinal diol unit and concomitant oxidation of the phenylselenide
      group to the corresponding selenoxide and syn beta-elimination. M1A and M1C were
      synthesized by the same strategy starting from 6-chloropurine 2'-deoxyriboside
      and 1-(2-deoxy-beta-d-erythro-pentofuranosyl)-4-(1H-1,2,4-triazol-1-yl)-2
      (1H)pyrimidinone, respectively. An advantage of this approach is that similar
      chemistry has been shown to be directly applicable to the synthesis of site
      specifically adducted oligonucleotides containing activated nucleobases such as
      those used in this study. This strategy may offer an improved synthesis to
      oligonucleotides containing M1G and a feasible approach to M1A and M1C containing
      oligonucleotides.

PMID- 14967002
TI  - Mechanism-based inactivation of cytochrome P450 3A4 by 4-ipomeanol.
AB  - Earlier phase I and II clinical studies showed that 4-ipomeanol produced
      selective hepatotoxicity. To investigate the mechanism of bioactivation of 4
      ipomeanol, we thoroughly studied the interaction of 4-ipomeanol with human
      cytochrome P450 3A4 (EC 1.14.14.1). 4-Ipomeanol produced a time- and
      concentration-dependent inactivation of P450 3A4. More than 80% of the P450 3A4
      activity was lost after its incubation with 4-ipomeanol at the concentration of
      75 microM in 12 min. The inactivation was characterized by a rate of inactivation
      (kinact) of 0.15 min(-1) and by an inactivation potency (KI) of 20 microM. In
      addition, the inhibition of P450 3A4 by 4-ipomeanol was NADPH-dependent and
      irreversible. Glutathione, catalase, and superoxide dismutase failed to protect
      P450 3A4 from inactivation by 4-ipomeanol. The presence of testosterone, a
      substrate of P450 3A4, protected the enzyme from inactivation. The estimated
      partition ratio of the inactivation was approximately 257. Covalent binding
      studies demonstrated that reactive metabolites of 4-ipomeanol modified P450 3A4
      but not P450 reductase (EC 1.6.2.4). The stoichiometry of binding between
      reactive metabolites of radiolabeled 4-ipomeanol and P450 3A4 was approximately
      1.5:1. In addition to P450 3A4, reactive metabolites of 4-ipomeanol were found to
      covalently bind to other proteins. 4-Ipomeanol failed to inactivate P450 1A2 in
      human liver microsomes. In conclusion, 4-ipomeanol irreversibly inhibited P450
      3A4, and it was characterized as a mechanism-based inactivator of P450 3A4. This
      finding facilitates the understanding of the mechanism of bioactivation of 4
      ipomeanol by human hepatic enzymes.

PMID- 14967003
TI  - Multidrug resistance-associated protein 2 (MRP2) enhances 4-hydroxynonenal
      induced toxicity in Madin-Darby canine kidney II cells.
AB  - 4-Hydroxy-trans-2,3-nonenal (HNE) is a toxic end product of lipid peroxidation.
      This multifunctional aldehyde reacts with proteins, phospholipids, and nucleic
      acids, consequently activating/inactivating enzymes, affecting signal
      transduction and gene expression. HNE is mainly detoxified by glutathione (GSH)
      conjugation. In our previous report, we showed that GSH conjugates of 4
      hydroxynonenal (HNE-SG) are substrates of multidrug resistance-associated protein
      2 (MRP2). MRP2 has been shown to export HNE-SG conjugates into the extracellular
      space. In the present study, the role of MRP2 in the detoxification of HNE was
      studied using Madin-Darby canine kidney II (MDCK II) cells expressing human MRP2.
      MRP2 reduced the intracellular accumulation of HNE-SG conjugate but unexpectedly
      increased the susceptibility of cells to HNE. The viability of cells was reduced
      to approximately 70% in the presence of 62.5 microM HNE in MDCK II cells
      expressing MRP2, whereas MDCK II cells remained unaffected. MRP2 accelerated the
      elimination of intracellular GSH via a conjugation reaction with HNE (half-life
      of GSH was 30.1 and 12.2 min for MDCK II cells and MDCK II cells expressing MRP2,
      respectively). Moreover, the consumption of GSH was unlimited in MDCK II cells
      expressing MRP2, finally resulting in necrosis. These results indicate that MRP2
      has an adverse effect during the detoxification of HNE in MDCK II cells and
      suggest that expression of MRP2 may enhance the damage caused by oxidative
      stress.

PMID- 14967004
TI  - Use of metabonomics to identify impaired fatty acid metabolism as the mechanism
      of a drug-induced toxicity.
AB  - An increased diversity of therapeutic targets in the pharmaceutical industry in
      recent years has led to a greater diversity of toxicological effects. This, and
      the increased pace of drug discovery, leads to a need for new technologies for
      the rapid elucidation of toxicological mechanisms. As part of an evaluation of
      the utility of metabonomics in drug safety assessment, 1H NMR spectra were
      acquired on urine and liver tissue samples obtained from rats administered
      vehicle or a development compound (MrkA) previously shown to induce
      hepatotoxicity in several animal species. Multivariate statistical analysis of
      the urinary NMR data clearly discriminated drug-treated from control animals, due
      to a depletion in tricarboxylic acid cycle intermediates, and the appearance of
      medium chain dicarboxylic acids. High-resolution magic angle spinning NMR data
      acquired on liver samples exhibited elevated triglyceride levels that were
      correlated with changes in the urinary NMR data. Urinary dicarboxylic aciduria is
      associated with defective metabolism of fatty acids; subsequent in vitro
      experiments confirmed that MrkA impairs fatty acid metabolism. The successful
      application of metabonomics to characterize an otherwise ill-defined mechanism of
      drug-induced toxicity supports the practicality of this approach for resolving
      toxicity issues for drugs in discovery and development.

PMID- 14967005
TI  - Mechanism-based inactivation of cytochrome P450 2D6 by 1-[(2-ethyl-4-methyl-1H
      imidazol-5-yl)methyl]- 4-[4-(trifluoromethyl)-2-pyridinyl]piperazine: kinetic
      characterization and evidence for apoprotein adduction.
AB  - The kinetics for inactivation of cytochrome P450 2D6 by (1-[(2-ethyl-4-methyl-1H
      imidazol-5-yl)methyl]-4-[4-(trifluoromethyl)-2-pyridinyl]piperazine (EMTPP) were
      characterized, and the mechanism was determined in an effort to understand the
      observed time-based inactivation. Loss of dextromethorphan O-demethylase activity
      following coincubation with EMTPP followed pseudo-first-order kinetics and was
      both NADPH- and EMTPP-dependent. Inactivation was characterized by an apparent Ki
      of 5.5 microM with a maximal rate constant for inactivation (kinact) of 0.09 min(
      1), a t1/2 of 7.7 min, and a partition ratio of approximately 99. P450 2D6
      inactivation was unaffected by coincubation with exogenous nucleophiles or
      reactive oxygen scavengers and was protected by the competing inhibitors N-4
      (trifluoromethyl)benzyl quinidinium bromide and quinidine. After a 30 min
      incubation with 100 microM EMTPP, dextromethorphan O-demethylase activity was
      decreased approximately 76%, with a disproportionate loss ( approximately 35%) in
      carbon monoxide binding. Additional mechanistic studies showed no evidence of
      either metabolite inhibitory complex formation or heme adduction. However, a P450
      2D6 apoprotein adduct was characterized that had a mass shift relative to
      unadducted P450 2D6 apoprotein consistent with the molecular mass of EMTPP (353
      Da). In vitro metabolism studies revealed that EMTPP is susceptible to P450 2D6
      mediated hydroxylation and dehydrogenation, postulated to both form via initial
      hydrogen atom abstraction from the alpha-carbon of the imidazole ethyl
      substituent. Additional studies demonstrated that while a dehydrogenated EMTPP
      metabolite was apparently stable and observable, we propose that a thermodynamic
      partitioning may exist, which results in formation of a second dehydrogenated
      imidazo-methide-like metabolite that may serve as the reactive species causing
      mechanism-based inactivation of P450 2D6. Last, trapping studies with EMTPP
      yielded an N-acetyl cysteine conjugate, which upon tandem MS and NMR analysis
      revealed adduction to the alpha-carbon of the imidazole ethyl substituent.
      Overall, evidence suggests that nucleophilic attack of an imidazo-methide-like
      intermediate by a P450 2D6 active site residue leads to apoprotein adduction and
      consequent inactivation.

PMID- 14967006
TI  - Organic nitrites and NO: inhibition of lipid peroxidation and radical reactions.
AB  - Organic nitrites, such as i-amyl nitrite (IAN), are nitrovasodilator drugs used
      both clinically and recreationally. Nitrites are also chemically reasonable
      biological products of NO metabolism, in particular in both inhibition of lipid
      peroxidation by NO and induction of lipid peroxidation by peroxynitrite and NO2.
      Nitrites are also potential products of biomolecule nitrosation and intermediates
      in biotransformation of nitrate vasodilators. Although mechanisms can be drawn
      for both prooxidant and antioxidant activity, IAN has been observed to inhibit
      lipid peroxidation in a variety of systems. To test if the antioxidant activity
      of nitrites results from NO release alone, inhibition of lipid peroxidation was
      studied for four organic nitrites and four NO donor NONOates. Iron-induced lipid
      peroxidation in synaptosomal tissue homogenates and azo compound-initiated lipid
      peroxidation in liposomes and linoleic acid SDS comicelles were examined. Lipid
      peroxidation was quantified by TBARS and oxygen uptake analysis. A good
      correlation of rate of NO release with IC50 for inhibition of lipid peroxidation
      was observed for the NONOates, compatible with lipid radical chain termination by
      NO, for which a chain termination stoichiometry of 0.4-0.5 mol of lipid peroxyl
      radicals per mole of NO was determined. In neutral aqueous solution, nitrites
      also spontaneously released NO as measured by chemiluminescence; however, no
      correlation was observed between the rate constants of NO release for the
      nitrites and their inhibitor potency toward lipid peroxidation. Long chain
      nitrites were seen to be relatively good inhibitors of lipid peroxidation by
      mechanisms that must involve factors in addition to simple homolysis to release
      NO. Evidence for direct alpha-hydrogen atom abstraction from the nitrite by
      peroxyl radicals was obtained by analysis of aldehyde products and supported by
      MO calculations. The data suggest that lipid nitrites formed as NO chain
      termination products have the capacity to further inhibit lipid peroxidation and
      to release NO.

PMID- 14967007
TI  - Half-life and DNA strand scission products of 2-deoxyribonolactone oxidative DNA
      damage lesions.
AB  - Reactive oxygen species lead to oxidative damage of the nucleobase and sugar
      components of nucleotides in double-stranded DNA. The 2-deoxyribonolactone (or
      oxidized abasic site) lesion results from oxidation of the C-1' position of DNA
      nucleotides and has been implicated in DNA strand scission, mutagenesis, and
      covalent cross-linking to DNA binding proteins. We previously described a
      strategy for the synthesis of DNA-containing deoxyribonolactone lesions. We now
      report an improved method for the site specific photochemical generation of
      deoxyribonolactone sites within DNA oligonucleotides and utilize these synthetic
      oligonucleotides to characterize the products and rates of DNA strand scission at
      the lactone lesion under simulated physiological conditions. A C-1' nitroveratryl
      cyanohydrin phosphoramidite analogue was synthesized and used for the preparation
      of DNA containing a photochemically "caged" lactone precursor. Irradiation at 350
      nm quantitatively converted the caged analogue into the deoxyribonolactone
      lesion. The methodology was validated by RP-HPLC and MALDI-TOF mass spectrometry.
      Incubation of deoxyribonolactone-containing DNA under simulated physiological
      conditions gave rise to DNA fragmentation by two consecutive elimination
      reactions. The DNA-containing products resulting from DNA cleavage at the
      deoxyribonolactone site were isolated by PAGE and unambiguously characterized by
      MALDI-TOF MS and chemical fingerprinting assays. The rate of DNA strand scission
      at the deoxyribonolactone site was measured in single- and double-stranded DNA
      under simulated physiological conditions: DNA cleavage occurred with a half-life
      of approximately 20 h in single-stranded DNA and 32-54 h in duplex DNA, dependent
      on the identity of the deoxynucleotide paired opposite the lesion site. The
      initial alpha,beta-elimination reaction was shown to be the rate-determining step
      for the formation of methylene furanone and phosphorylated DNA products. These
      investigations demonstrated that the deoxyribonolactone site represents a labile
      lesion under simulated physiological conditions and forms the basis for further
      studies of the biological effects of this oxidative DNA damage lesion.

PMID- 14967008
TI  - The protective role of intracellular GSH status in the arsenite-induced vascular
      endothelial dysfunction.
AB  - In this study, we used porcine aortic endothelial cells (PAECs) as an in vitro
      system to investigate the role of intracellular GSH status in arsenite-induced
      vascular endothelial damage. Exposure of PAECs to l-buthionine sulfoximine (BSO),
      an inhibitor of gamma-glutamylcysteine synthetase (gamma-GCS), markedly enhanced
      the arsenite-induced cytotoxicity. The data implied that intracellular GSH might
      play an important role in protection of PAECs from arsenite-induced cytotoxicity.
      Low concentrations of arsenite exposure increased intracellular GSH
      concentrations, whereas high concentrations of arsenite exposure decreased
      intracellular GSH concentrations. We further modulated intracellular GSH
      concentration by using GSH modulators. N-Acetyl cysteine (NAC) and l-cystine
      (oxidized l-cysteine), by up-regulating intracellular GSH concentrations, were
      shown to protect PAECs from arsenite-induced cytotoxicity. On the other hand, BSO
      and monosodium glutamate (MSG), which down-regulated the intracellular GSH
      concentrations, further potentiated arsenite-induced cytotoxicity. Moreover,
      exposure of PAECs to NAC alleviated the arsenite-induced JNK/AP-1 activation and
      apoptosis, whereas exposure of PAECs to BSO enhanced the arsenite-induced JNK/AP
      1 activation and apoptosis. These results indicated that an increase in GSH
      content represented one of the detoxification mechanisms responding to arsenite
      exposure and probably played critical roles in the regulation of stress-response
      signaling molecules as well as in protection of PAECs from arsenite attack.

PMID- 14967009
TI  - A sensitive class specific immunoassay for the detection of pyrethroid
      metabolites in human urine.
AB  - The pyrethroids are one of the most heavily used insecticide classes in the
      world. It is important to develop sensitive and rapid analytical techniques for
      environmental monitoring and assessment of human exposure to these compounds.
      Because major pyrethroids contain a phenoxybenzyl group and phenoxybenzoic acid
      (PBA) is a common metabolite form or intermediate, PBA might be used as a
      biomarker of human exposure to pyrethroids. A sensitive and selective immunoassay
      for the common pyrethroid metabolite PBA was developed. Rabbits were immunized
      with 3-[4-(3-carboxyphenoxy)phenoxy] N-thyroglobulin ethylamine. All sera were
      screened against numerous coating antigens. The assay with the least interference
      and the best sensitivity was optimized and characterized. The average IC50 for
      free PBA was 1.65 ng/mL. No cross-reactivity was measured to parent pyrethroids
      and other metabolites. Urine matrix effects can be eliminated by simple dilution.
      Results from urine samples from exposed workers suggest that this PBA immunoassay
      might be suitable as a monitoring tool for human exposure to pyrethroids.

PMID- 14967010
TI  - Fast-flow EPR spectroscopic observation of the isoniazid, iproniazid, and
      phenylhydrazine hydrazyl radicals.
AB  - Hydrazyl radical intermediates have been suggested as important intermediates in
      the biochemistry of hydrazides and hydrazines. Although spin-trapping studies
      have intercepted those species previously, there has been no report of the direct
      observation of the unstable hydrazyl radicals of isoniazid and iproniazid. We
      have employed the fast-flow technique in electron paramagnetic resonance (EPR)
      spectroscopy to measure spectra for the short-lived hydrazyl radicals of a family
      of hydrazides, including the pharmacologically important compounds isoniazid and
      iproniazid, as well as for a series of phenylhydrazines. Our investigations of
      the phenylhydrazine radical and the related chloro-substituted analogues have
      allowed definitive assignments of the hyperfine coupling constants of that
      toxicologically important free radical. Theoretical values of hyperfine coupling
      constants, calculated by density functional formalism, provided a guide to
      assignments for the hydrazyl species and confirmed the experimentally based
      assignments for phenylhydrazyl radical.

PMID- 14967011
TI  - Ochratoxin A: lack of formation of covalent DNA adducts.
AB  - The mycotoxin ochratoxin A (OTA) is a potent nephrotoxin and renal carcinogen in
      rodents. However, the mechanism of OTA-induced tumor formation is unknown and
      conflicting results have been obtained regarding the potential of OTA to bind to
      DNA. OTA is poorly metabolized, and no reactive intermediates capable of
      interacting with DNA have been detected in vitro or in vivo. Recently, a
      hydroquinone/quinone redox couple and a carbon-bonded OTA-deoxyguanosine (OTA-dG)
      adduct formed by electrochemical oxidation and photoreaction of OTA have been
      reported and suggested to be involved in OTA carcinogenicity. This study was
      designed to characterize the role of DNA binding and to determine if formation of
      these derivatives occurs in vivo and in relevant activation systems in vitro
      using specific and sensitive methods. Horseradish peroxidase activation of OTA
      and its dechlorinated analogue ochratoxin B (OTB) yielded ochratoxin A
      hydroquinone (OTHQ), but the postulated OTA-dG adduct was not detectable using LC
      MS/MS. In support of this, no OTA-related DNA adducts were observed by 32P
      postlabeling. In vivo, only traces of OTHQ were found in the urine of male F344
      rats treated with high doses of OTA (2 mg/kg body wt) for 2 weeks, suggesting
      that this metabolite is not formed to a relevant extent. In agreement with the in
      vitro data, OTA-dG was not detected by LC-MS/MS in liver and kidney DNA extracted
      from treated animals. In addition, DNA binding of OTA and OTB was assessed in
      male rats given a single dose of 14C-OTA or 14C-OTB using accelerator mass
      spectrometry, a highly sensitive method for quantifying extremely low
      concentrations of radiocarbon. The 14C content in liver and kidney DNA from
      treated animals was not significantly different from controls, indicating that
      OTA does not form covalent DNA adducts in high yields. In summary, the results
      presented here demonstrate that DNA binding of OTA is not detectable with
      sensitive analytical methods and is unlikely to represent a mechanism for OTA
      induced tumor formation.

PMID- 14967012
TI  - Formation and urinary excretion of arsenic triglutathione and methylarsenic
      diglutathione.
AB  - Taking advantage of mice deficient in gamma-glutamyl transpeptidase that are
      unable to metabolize glutathione (GSH), we have identified two previously
      unrecognized urinary metabolites of arsenite: arsenic triglutathione and
      methylarsenic diglutathione. Following administration of sodium arsenite to these
      mice, approximately 60-70% of urinary arsenic is present as one of these GSH
      conjugates. We did not detect the dimethyl derivative, dimethyl arsenic GSH;
      however, dimethyl arsenic (DMAV) represented approximately 30% of urinary
      arsenic. Administration of buthionine sulfoximine, an inhibitor of GSH synthesis,
      to wild-type mice reduced urinary arsenic excretion by more than 50%, indicating
      the GSH dependence of arsenic metabolism, transport, or both. Rodents deficient
      in three known ABC family transporters (MRP1, MRP2, and MDR1a/1b) exhibited
      urinary arsenic levels similar or greater than those in wild-type rodents;
      however, administration of MK571, an MRP inhibitor, reduced urinary arsenic
      excretion by almost 50%. MK571-treated mice showed approximately 50% reduction of
      AsIII, MMAV, and AsV as compared to untreated wild-type controls, while DMAV
      levels were unchanged. These findings suggest that arsenic excretion is in part
      dependent on GSH and on an MRP transporter other than MRP1 or 2.

PMID- 14967013
TI  - Reactions of nitric oxide, peroxynitrite, and carbonate radicals with nitroxides
      and their corresponding oxoammonium cations.
AB  - Cyclic nitroxides effectively protect biological systems against radical-induced
      damage. However, the mechanism of the reactions of nitroxides with nitrogen
      derived reactive species and carbonate radicals is far from being elucidated. In
      the present study, the reactions of several representative piperidine- and
      pyrrolidine-based nitroxides with *NO, peroxynitrite, and CO3*- were
      investigated, and the results are as follows: (i) There is no evidence for any
      direct reaction between the nitroxides and the *NO. In the presence of oxygen,
      the nitroxides are readily oxidized by *NO2, which is formed as an intermediate
      during autoxidation of *NO. (ii) *NO reacts with the oxoammonium cations to form
      nitrite and the corresponding nitroxides with k1 = (9.8 +/- 0.2) x 10(3) and (3.7
      +/- 0.1) x 10(5) M(-1) s(-1) for the oxoammonium cations derived from 2,2,6,6
      tetramethylpiperidine-1-oxyl (TPO) and 3-carbamoyl-proxyl (3-CP), respectively.
      (iii) CO3*- oxidizes all nitroxides tested to their oxoammonium cations with
      similar rate constants of (4.0 +/- 0.5) x 10(8) M(-1) s(-1), which are about 3-4
      times higher than those determined for H-abstraction from the corresponding
      hydroxylamines TPO-H and 4-OH-TPO-H. (iv) Peroxynitrite ion does not react
      directly with the nitroxides but rather with their oxoammonium cations with k(10)
      = (6.0 +/- 0.9) x 10(6) and (2.7 +/- 0.9) x 10(6) M(-1) s(-1) for TPO+ and 3-CP+,
      respectively. These results provide a better insight into the complex mechanism
      of the reaction of peroxynitrite with nitroxides, which has been a controversial
      subject. The small effect of relatively low concentrations of nitroxides on the
      decomposition rate of peroxynitrite is attributed to their ability to scavenge
      efficiently *NO2 radicals, which are formed during the decomposition of
      peroxynitrite in the absence and in the presence of CO2. The oxoammonium cations,
      thus formed, are readily reduced back to the nitroxides by ONOO-, while forming
      *NO and O2. Hence, nitroxides act as true catalysts in diverting peroxynitrite
      decomposition from forming nitrating species to producing nitrosating ones.

PMID- 14967014
TI  - Characterization of S-(N,N-Dialkylaminocarbonyl)cysteine Adducts and Enzyme
      Inhibition Produced by Thiocarbamate Herbicides in the Rat.
AB  - Thiocarbamates are a major class of herbicides used extensively in the
      agricultural industry. It has been shown that thiocarbamates can form reactive
      sulfoxide and sulfone intermediates, which may be involved in the toxicity of
      thiocarbamates through covalent modification of cysteine and serine active sites
      of enzymes. Molinate has been shown to generate an S-hexahydro-1H-azepine-1
      carbonyl adduct on the Cys-125 residue of the beta2- and beta3-chains of rat
      globin analogous to that reported for disulfiram and to inhibit aldehyde
      dehydrogenase and nonspecific esterase activity. The present study examined
      whether other thiocarbamate herbicides produce similar covalent protein
      modifications and enzyme inhibition to that reported for molinate and whether S
      (N,N-dialkylaminocarbonyl)cysteine adduct levels are correlated to enzyme
      inhibition or the structure of thiocarbamate herbicides. Additionally, the
      potential of molinate to act as a peripheral demyelinating agent similar to
      disulfiram was evaluated. To address these aims, rats were exposed ip to
      molinate, vernolate, ethiolate, EPTC, or butylate for 5 days after which
      hemogloblin was isolated and analyzed for protein adducts using HPLC and matrix
      assisted laser desorption ionization time-of-flight mass spectrometry. In
      addition, brain, liver, and testes mitochondrial and microsomal fractions were
      assayed for nonspecific esterase, low Km ALDH, or total ALDH activities, and S
      (N,N-dialkylaminocarbonyl)cysteine adducts were measured by LC/MS/MS. For the
      neurotoxicity assessments, rats were administered molinate parenterally for
      subchronic periods and morphological evaluations performed on peripheral nerves.
      All of the thiocarbamates except butylate produced S-(N,N
      dialkylaminocarbonyl)cysteine adducts on globin and the quantity of adducts
      detected decreased with increasing size of the nitrogen substituents. In
      contrast, a clear relationship between cysteine modification in mitochondrial and
      microsomal samples to nitrogen substituents was not evident, and although
      molinate produced relatively high levels of adducts and esterase inhibition and
      butylate low levels of adducts and esterase inhibition for most samples, in
      general, the level of S-(N,N-dialkylaminocarbonyl)cysteine adducts did not appear
      to be related to enzyme inhibition. Molinate did not produce segmental
      demyelination in peripheral nerve, suggesting that molinate and possibly other
      thiocarbamates do not share the neurotoxic potential of dithiocarbamates.

PMID- 14967015
TI  - A modified immuno-enriched 32P-postlabeling method for analyzing the
      malondialdehyde-deoxyguanosine adduct, 3-(2-deoxy-beta-D-erythro-pentofuranosyl)-
      pyrimido[1,2-alpha]purin-10(3H)one in human tissue samples.
AB  - The malondialdehyde-modified DNA adduct, 3-(2-deoxy-beta-d-erythro
      pentofuranosyl)pyrimido[1,2-alpha]purin-10(3H)one (M1dG) has been detected in
      human tissues and is considered to be a promising biomarker for estimating lipid
      peroxidation-induced DNA damage. With the aim to analyze the M1dG in small
      amounts of DNA (<10 microg) and to improve the sensitivity, we have developed an
      immuno-enriched 32P-postlabeling HPLC method. The main modifications included the
      following steps: (i) an optimization of the immunoenrichment conditions using a
      monoclonal antibody (MAb D 10A1), (ii) a single labeling step of the purified
      M1dG 3'-monophosphate to its 5'-monophosphate at pH 6.8, (iii) the addition of O4
      ethylthymidine 3'-monophosphate as an internal standard, and (iv) a
      prepurification of the labeled adduct on a polyethyleneimine minicolumn before
      HPLC analysis. With this protocol, the percent recovery of M1dG was found to be
      approximately 70 +/- 20; the detection limit in biological samples was
      approximately 200 amol M1dG from 10 microg of DNA, corresponding to 6
      adducts/10(9) nucleotides. In conclusion, our modified method shows a high
      sensitivity and specificity; when applied to human breast and liver tissue
      samples, background levels of the M1dG could be reproducibly detected. This
      ultrasensitive detection method is thus suitable for applications in human
      biomonitoring and molecular epidemiology studies.

PMID- 14967018
TI  - Chimeragenesis of the fatty acid binding site of cytochrome P450BM3. Replacement
      of residues 73-84 with the homologous residues from the insect cytochrome P450
      CYP4C7.
AB  - A protein fragment of P450BM3 (residues 73-84) which participates in palmitoleate
      binding was subjected to scanning chimeragenesis. Amino acids 73-84, 73-78, 75
      80, and 78-82 were replaced with the homologous fragments of the insect terpenoid
      hydroxylase CYP4C7. The four chimeric proteins, C(73-84), C(73-78), C(75-80), and
      C(78-82), were expressed, purified, and characterized. All the chimeric proteins
      contained all the cofactors and catalyzed monooxygenation of palmitate and of the
      sesquiterpene farnesol. Chimeragenesis altered substrate binding as shown by the
      changes in the amplitude of the palmitate-induced type I spectral shift. C(78-82)
      had monooxygenase activities close to those of P450BM3, while the rest of the
      chimeric proteins had monooxygenase activities that were inhibited relative to
      that of wild-type P450BM3. The extent of inhibition of the chimeric proteins
      varied depending on the substrate, and in the case of C(73-84), farnesol and
      palmitate oxidation was inhibited by 1 and 4 orders of magnitude, respectively.
      (1)H NMR spectroscopy and GC-MS were used to identify products of farnesol and
      palmitate oxidation. Wild-type P450BM3 and all chimeric proteins catalyzed
      oxidation of farnesol with formation of 9-hydroxyfarnesol and farnesol 10,11- and
      2,3-epoxides. Three of the four chimeric proteins also formed a new compound, 5
      hydroxyfarnesol, which was the major product in the case of C(73-78). In addition
      to hydroxylation of the C13-C15 atoms, the chimeric enzymes catalyze significant
      hydroxylation of the C10-C12 atoms of palmitate. In the case of C(78-82), the
      rates of formation of 11- and 12-hydroxypalmitates increased 7-fold compared to
      that of wild-type P450BM3 to 106 and 212 min(-)(1), respectively, while the rate
      of 10-hydroxypalmitate synthesis increased from zero to 106 min(-)(1). Thus,
      chimeragenesis of the region of residues 73-84 of the substrate binding site
      shifted the regiospecificity of substrate oxidation toward the center of the
      farnesol and palmitate molecules.

PMID- 14967017
TI  - Side chains at the membrane-water interface modulate the signaling state of a
      transmembrane receptor.
AB  - Previous model studies of peptides and proteins have shown that protein-lipid
      interactions, primarily involving amino acid side chains near the membrane-water
      interface, modulate the position of transmembrane helices in bilayers. The
      present study examines whether such interfacial side chains stabilize the
      signaling states of a transmembrane signaling helix in a representative receptor,
      the aspartate receptor of bacterial chemotaxis. To examine the functional roles
      of signaling helix side chains at the periplasmic and cytoplasmic membrane-water
      interfaces, arginine and cysteine substitutions were scanned through these two
      interfacial regions. The chemical reactivities of the cysteine residues were
      first measured to determine the positions at which the helix crosses the membrane
      water interface in both the periplasmic and cytoplasmic compartments.
      Subsequently, two antisymmetric in vitro activity measurements were carried out
      to determine the effect of each interfacial arginine or cysteine substitution on
      receptor signaling. Substitutions that stabilize the receptor on-state cause
      upregulation of receptor-coupled kinase activity and inhibition of methylation at
      receptor adaptation sites, while substitutions that stabilize the off-state have
      the opposite effects on these two activities. Notably, four substitutions at
      aromatic tryptophan and phenylalanine positions buried in the membrane near the
      membrane-water interface were found to stabilize the native on- or off-signaling
      state. The striking ability of these substitutions to drive the receptor toward a
      specific signaling state indicates that interfacial side chains are highly
      optimized to correctly position the native signaling helix in the membrane and to
      allow normal switching between the on- and off-signaling states. The analogous
      substitutions in model transmembrane helices are known to drive small piston-type
      displacements of the helix normal to the membrane. Thus, the simplest molecular
      interpretation of the present findings is that the signal-stabilizing
      substitutions drive piston displacements of the signaling helix, providing
      further support for the piston model for transmembrane signaling in bacterial
      chemoreceptors. More generally, the findings indicate that the interfacial
      phenylalanine, tryptophan, and arginine side chains widespread in the
      transmembrane alpha-helices of receptors, channels, and transporters can play
      important roles in modulating transitions between signaling and conformational
      states.

PMID- 14967019
TI  - A high-field EPR study of P700+ in wild-type and mutant photosystem I from
      Chlamydomonas reinhardtii.
AB  - High-frequency, high-field EPR at 330 GHz was used to study the photo-oxidized
      primary donor of photosystem I (P(700)(+)(*)) in wild-type and mutant forms of
      photosystem I in the green alga Chlamydomonas reinhardtii. The main focus was the
      substitution of the axial ligand of the chlorophyll a and chlorophyll a'
      molecules that form the P(700) heterodimer. Specifically, we examined PsaA-H676Q,
      in which the histidine axial ligand of the A-side chlorophyll a' (P(A)) is
      replaced with glutamine, and PsaB-H656Q, with a similar replacement of the axial
      ligand of the B-side chlorophyll a (P(B)), as well as the double mutant (PsaA
      H676Q/PsaB-H656Q), in which both axial ligands were replaced. We also examined
      the PsaA-T739A mutant, which replaces a threonine residue hydrogen-bonded to the
      13(1)-keto group of P(A) with an alanine residue. The principal g-tensor
      components of the P(700)(+)(*) radical determined in these mutants and in wild
      type photosystem I were compared with each other, with the monomeric chlorophyll
      cation radical (Chl(z)(+)(*)) in photosystem II, and with recent theoretical
      calculations for different model structures of the chlorophyll a(+) cation
      radical. In mutants with a modified P(B) axial ligand, the g(zz) component of
      P(700)(+)(*) was shifted down by up to 2 x 10(-4), while mutations near P(A) had
      no significant effect. We discuss the shift of the g(zz) component in terms of a
      model with a highly asymmetric distribution of unpaired electron spin in the
      P(700)(+)(*) radical cation, mostly localized on P(B), and a deviation of the
      P(B) chlorophyll structure from planarity due to the axial ligand.

PMID- 14967020
TI  - A conformational mimic of the MgATP-bound "on state" of the nitrogenase iron
      protein.
AB  - The crystal structure of a nitrogenase Fe protein single site deletion variant
      reveals a distinctly new conformation of the Fe protein and indicates that, upon
      binding of MgATP, the Fe protein undergoes a dramatic conformational change that
      is largely manifested in the rigid-body reorientation of the homodimeric Fe
      protein subunits with respect to one another. The observed conformational state
      allows the rationalization of a model of structurally and chemically
      complementary interactions that occur upon initial complex formation with the
      MoFe protein component that are distinct from the protein-protein interactions
      that have been characterized previously for stabilized nitrogenase complexes. The
      crystallographic results, in combination with complementary UV-visible
      absorption, EPR, and resonance Raman spectroscopic data, indicate that the [4Fe
      4S] cluster of both the Fe protein deletion variant and the native Fe protein in
      the presence of MgATP can reversibly cycle between a regular cubane-type [4Fe-4S]
      cluster in the reduced state and a cleaved form involving two [2Fe-2S] fragments
      in the oxidized state. Resonance Raman studies indicate that this novel cluster
      conversion is induced by glycerol, and the crystallographic data suggest that
      glycerol is bound as a bridging bidentate ligand to both [2Fe-2S] cluster
      fragments in the oxidized state.

PMID- 14967021
TI  - Phe393 mutants of cytochrome P450 BM3 with modified heme redox potentials have
      altered heme vinyl and propionate conformations.
AB  - It has been well established that the heme redox potential is affected by many
      different factors. Among others, it is sensitive to the proximal heme ligand and
      the conformation of the propionate and vinyl groups. In the cytochrome P450 BM3
      heme domain, substitution of the highly conserved phenylalanine 393 results in a
      dramatic change in the heme redox potential [Ost, T. W. B., Miles, C. S., Munro,
      A. W., Murdoch, J., Reid, G. A., and Chapman, S. K. (2001) Biochemistry 40, 13421
      13429]. We have used resonance Raman spectroscopy to characterize heme structural
      changes and modification of heme interactions with the protein matrix that are
      induced by the F393 substitutions and to determine their correlation with the
      heme redox potential. Our results show that the Fe-S stretching frequency of the
      5-coordinated, high-spin ferric heme is not affected by the mutations, suggesting
      that the electron density in the Fe-S bond in this state is not affected by the
      F393 mutation and is not a good indicator of the heme redox potential. Substrate
      binding perturbs the hydrogen bonding between one propionate group and the
      protein matrix and correlates to both the size of residue 393 and the heme redox
      potential. However, heme reduction does not affect the conformation of the
      propionate groups. Although the conformation of the vinyl groups is not affected
      much by substrate binding, their conformation changes from mainly out-of-plane to
      predominantly in-plane upon heme reduction. The extent of these conformational
      changes correlates strongly with the size of the 393 residue and the heme redox
      potential, suggesting that steric interaction between this residue and the vinyl
      groups may be of importance in regulating the heme redox potential in the P450
      BM3 heme domain. Further implications of our findings for the change in redox
      potential upon mutation of F393 will be discussed.

PMID- 14967022
TI  - Rhodobacter capsulatus photoactive yellow protein: genetic context, spectral and
      kinetics characterization, and mutagenesis.
AB  - A gene for photoactive yellow protein (PYP) was previously cloned from
      Rhodobacter capsulatus (Rc), and we have now found it to be associated with genes
      for gas vesicle formation in the recently completed genome sequence. However, the
      PYP had not been characterized as a protein. We have now produced the recombinant
      RcPYP in Escherichia coli as a glutathione-S-transferase (GST) fusion protein,
      along with the biosynthetic enzymes, resulting in the formation of holo-RcPYP
      following cleavage of the GST tag. The absorption spectrum (with characteristic
      peaks at 435 and 375 nm) and the photocycle kinetics, initiated by a laser flash
      at 445 nm, are generally similar to those of Rhodobacter sphaeroides (RsPYP) but
      are significantly different from those of the prototypic PYP from Halorhodospira
      halophila (HhPYP), which has a single peak at 446 nm and has slower recovery.
      RcPYP also is photoactive when excited with near-ultraviolet laser light, but the
      end point is then above the preflash baseline. This suggests that some of the PYP
      chromophore is present in the cis-protonated conformation in the resting state.
      The excess 435 nm form in RcPYP, built up from repetitive 365 nm laser flashes,
      returns to the preflash baseline with an estimated half-life of 2 h, which is
      markedly slower than that for the same reaction in RsPYP. Met100 has been
      reported to facilitate cis-trans isomerization in HhPYP, yet both Rc and RsPYPs
      have Lys and Gly substitutions at positions 99 and 100 (using HhPYP numbering
      throughout) and have 100-fold faster recovery kinetics than does HhPYP. However,
      the G100M and K99Q mutations of RcPYP have virtually no effect on kinetics.
      Apparently, the RcPYP M100 is in a different conformation, as was recently found
      for the PYP domain of Rhodocista centenaria Ppr. The cumulative results show that
      the two Rhodobacter PYPs are clearly distinct from the other species of PYP that
      have been characterized. These properties also suggest a different functional
      role, that we postulate to be in regulation of gas vesicle genes, which are known
      to be light-regulated in other species.

PMID- 14967023
TI  - Crystal structure of the S-adenosylmethionine synthetase ternary complex: a novel
      catalytic mechanism of S-adenosylmethionine synthesis from ATP and Met.
AB  - S-Adenosylmethionine synthetase (MAT) catalyzes formation of S-adenosylmethionine
      (SAM) from ATP and l-methionine (Met) and hydrolysis of tripolyphosphate to PP(i)
      and P(i). Escherichia coli MAT (eMAT) has been crystallized with the ATP analogue
      AMPPNP and Met, and the crystal structure has been determined at 2.5 A
      resolution. eMAT is a dimer of dimers and has a 222 symmetry. Each active site
      contains the products SAM and PPNP. A modeling study indicates that the
      substrates (AMPPNP and Met) can bind at the same sites as the products, and only
      a small conformation change of the ribose ring is needed for conversion of the
      substrates to the products. On the basis of the ternary complex structure and a
      modeling study, a novel catalytic mechanism of SAM formation is proposed. In the
      mechanism, neutral His14 acts as an acid to cleave the C5'-O5' bond of ATP while
      simultaneously a change in the ribose ring conformation from C4'-exo to C3'-endo
      occurs, and the S of Met makes a nucleophilic attack on the C5' to form SAM. All
      essential amino acid residues for substrate binding found in eMAT are conserved
      in the rat liver enzyme, indicating that the bacterial and mammalian enzymes have
      the same catalytic mechanism. However, a catalytic mechanism proposed recently by
      Gonzalez et al. based on the structures of three ternary complexes of rat liver
      MAT [Gonzalez, B., Pajares, M. A., Hermoso, J. A., Guillerm, D., Guillerm, G.,
      and Sanz-Aparicio. J. (2003) J. Mol. Biol. 331, 407] is substantially different
      from our mechanism.

PMID- 14967024
TI  - Structure and assembly of designed beta-hairpin peptides in crystals as models
      for beta-sheet aggregation.
AB  - De novo designed beta-hairpin peptides have generally been recalcitrant to
      crystallization. The crystal structures of four synthetic peptide beta-hairpins,
      Boc-Leu-Val-Val-DPro-Gly-Leu-Phe-Val-OMe (1), Boc-Leu-Phe-Val-DPro-Ala-Leu-Phe
      Val-OMe (2), Boc-Leu-Val-Val-DPro-Aib-Leu-Val-Val-OMe (3), and Boc-Met-Leu-Phe
      Val-DPro-Ala-Leu-Val-Val-Phe-OMe (4), are described. The centrally positioned
      DPro-Xxx segment promotes prime beta-turn formation, thereby nucleating beta
      hairpin structures. In all four peptides well-defined beta-hairpins nucleated by
      central type II' DPro-Xxx beta-turns have been characterized by X-ray
      diffraction, providing a view of eight crystallographically independent hairpins.
      In peptides 1-3 three intramolecular cross-strand hydrogen bonds stabilized the
      observed beta-hairpin, with some fraying of the structures at the termini. In
      peptide 4, four intramolecular cross-strand hydrogen bonds stabilized the
      hairpin. Peptides 1-4 reveal common features of packing of beta-hairpins into
      crystals. Two-dimensional sheet formation mediated by intermolecular hydrogen
      bonds formed between antiparallel strands of adjacent molecule is a recurrent
      theme. The packing of two-dimensional sheets into the crystals is mediated in the
      third dimension by bridging solvents and interactions of projecting side chains,
      which are oriented on either face of the sheet. In all cases, solvation of the
      central DPro-Xxx peptide unit beta-turn is observed. The hairpins formed in the
      octapeptides are significantly buckled as compared to the larger hairpin in
      peptide 4, which is much flatter. The crystal structures provide insights into
      the possible modes of beta-sheet packing in regular crystalline arrays, which may
      provide a starting point for understanding beta-sandwich and cross-beta
      structures in amyloid fibrils.

PMID- 14967025
TI  - Solution structure of the coxsackievirus and adenovirus receptor domain 1.
AB  - The coxsackievirus and adenovirus receptor (CAR) mediates entry of coxsackievirus
      B (CVB) and adenovirus (Ad). The normal cellular function of CAR, which is
      expressed in a wide variety of tissue types, is thought to involve homophilic
      cell adhesion in the developing brain. The extracellular domain of CAR consists
      of two immunoglobulin (Ig) domains termed CAR-D1 and CAR-D2. CAR-D1 is shown by
      sedimentation velocity to be monomeric at pH 3.0. The solution structure and the
      dynamic properties of monomeric CAR-D1 have been determined by NMR spectroscopy
      at pH 3.0. The determinants of the CAR-D1 monomer-dimer equilibrium, as well as
      the binding site of CVB and Ad on CAR, are discussed in light of the monomer
      structure.

PMID- 14967026
TI  - NMR solution structure of a peptide from the mdm-2 binding domain of the p53
      protein that is selectively cytotoxic to cancer cells.
AB  - We have recently found that a peptide from the mdm-2 binding domain of the p53
      protein induced rapid membranolytic necrosis of a variety of different human
      cancer cell lines. To determine the role of solution structure in this peptide's
      selective and rapid tumor membrane disruptive behavior, we have performed two
      dimensional NMR on a 32-residue sequence called PNC-27, in both an aqueous
      cytosolic-like and a mixed organic membrane-mimetic solution environment. In an
      aqueous milieu, PNC-27 contains three alpha-helical domains connected by loop
      structures, forming an S shape, and another similar structure with less helical
      structure. In a solution environment simulating a membrane, the helical domains
      found in water increase in length, forming three classes of structures, all of
      which form a U-shaped helix-coil-helix ensemble. In both solvent systems, this
      peptide forms amphipathic structures such that its hydrophobic residues coalesce
      on one face while the polar residues aggregate on the opposite face. The ability
      to form these unique structures in these two solution environments may allow the
      PNC-27 peptide to selectively and rapidly disrupt cancer cell membranes.

PMID- 14967027
TI  - Mechanism of activation of human heparanase investigated by protein engineering.
AB  - The aim of this study was to investigate the mechanism of activation of human
      heparanase, a key player in heparan sulfate degradation, thought to be involved
      in normal and pathologic cell migration processes. Active heparanase arises as a
      product of a series of proteolytic processing events. Upon removal of the signal
      peptide, the resulting, poorly active 65 kDa species undergoes the excision of an
      intervening 6 kDa fragment generating an 8 kDa polypeptide and a 50 kDa
      polypeptide, forming the fully active heterodimer. By engineering of tobacco etch
      virus protease cleavage sites at the N- and C-terminal junctions of the 6 kDa
      fragment, we were able to reproduce the proteolytic activation of heparanase in
      vitro using purified components, showing that cleavage at both sites leads to
      activation in the absence of additional factors. On the basis of multiple
      sequence alignment of the N-terminal fragment, we conclude that the first
      beta/alpha/beta element of the postulated TIM barrel fold is contributed by the 8
      kDa subunit and that the excised 6 kDa fragment connects the second beta-strand
      and the second alpha-helix of the barrel. Substituting the 6 kDa fragment with
      the topologically equivalent loop from Hirudinaria manillensis hyaluronidase or
      connecting the 8 and 50 kDa fragments with a spacer of three glycine-serine pairs
      resulted in constitutively active, single-chain heparanases which were comparable
      to the processed, heterodimeric enzyme with regard to specific activity,
      chromatographic profile of hydrolysis products, complete inhibition at NaCl
      concentrations above 600 mM, a pH optimum of pH approximately 5, and inhibition
      by heparin with IC(50)s of 0.9-1.5 ng/microL. We conclude that (1) the heparanase
      heterodimer (alpha/beta)(8)-TIM barrel fold is contributed by both 8 and 50 kDa
      subunits with the 6 kDa connecting fragment leading to inhibition of heparanase
      by possibly obstructing access to the active site, (2) proteolytic excision of
      the 6 kDa fragment is necessary and sufficient for heparanase activation, and (3)
      our findings open the way to the production of recombinant, constitutively active
      single-chain heparanase for structural studies and for the identification of
      inhibitors.

PMID- 14967028
TI  - Molecular modeling of CPT-11 metabolism by carboxylesterases (CEs): use of pnb CE
      as a model.
AB  - CPT-11 is a prodrug that is converted in vivo to the topoisomerase I poison SN-38
      by carboxylesterases (CEs). Among the CEs studied thus far, a rabbit liver CE
      (rCE) converts CPT-11 to SN-38 most efficiently. Despite extensive sequence
      homology, however, the human homologues of this protein, hCE1 and hiCE,
      metabolize CPT-11 with significantly lower efficiencies. To understand these
      differences in drug metabolism, we wanted to generate mutations at individual
      amino acid residues to assess the effects of these mutations on CPT-11
      conversion. We identified a Bacillus subtilis protein (pnb CE) that could be used
      as a model for the mammalian CEs. We demonstrated that pnb CE, when expressed in
      Escherichia coli, metabolizes both the small esterase substrate o-NPA and the
      bulky prodrug CPT-11. Furthermore, we found that the pnb CE and rCE crystal
      structures show an only 2.4 A rmsd variation over 400 residues of the alpha
      carbon trace. Using the pnb CE model, we demonstrated that the "side-door"
      residues, S218 and L362, and the corresponding residues in rCE, L252 and L424,
      were important in CPT-11 metabolism. Furthermore, we found that at position 218
      or 252 the size of the residue, and at position 362 or 424 the hydrophobicity and
      charge of the residue, were the predominant factors in influencing drug
      activation. The most significant change in CPT-11 metabolism was observed with
      the L424R variant rCE that converted 10-fold less CPT-11 than the wild-type
      protein. As a result, COS-7 cells expressing this mutant were 3-fold less
      sensitive to CPT-11 than COS-7 cells expressing the wild-type protein.

PMID- 14967029
TI  - Esters of mandelic acid as substrates for (S)-mandelate dehydrogenase from
      Pseudomonas putida: implications for the reaction mechanism.
AB  - (S)-Mandelate dehydrogenase (MDH) from Pseudomonas putida is a flavin
      mononucleotide (FMN)-dependent enzyme that oxidizes (S)-mandelate to
      benzoylformate. In this work, we show that the ethyl and methyl esters of (S)
      mandelic acid are substrates for MDH. Although the binding affinity of the
      neutral esters is 25-50-fold lower relative to the negatively charged (S)
      mandelate, they are oxidized with comparable k(cat)s. Substrate analogues in
      which the carbonyl group on the C-1 carbon is replaced by other electron
      withdrawing groups were not substrates. The requirement of a carbonyl group on
      the C-1 carbon in a substrate suggests that the negative charge developed during
      the reaction is stabilized by delocalization to the carbonyl oxygen. Arg277, a
      residue that is important in both binding and transition state stabilization for
      the activity with (S)-mandelate, is also critical for transition state
      stabilization for the esters, but not for their binding affinity. We previously
      showed that the substrate oxidation half-reaction with (S)-mandelate has two rate
      limiting steps of similar activation energies and proceeds through the formation
      of a charge-transfer complex of an electron-rich donor and oxidized FMN [Dewanti,
      A. R., and Mitra, B. (2003) Biochemistry 42, 12893-12901]. This charge-transfer
      intermediate was observed with the neutral esters as well. The observation of
      this electron-rich intermediate for the oxidation of an uncharged substrate to an
      uncharged product, as well as the critical role of Arg277 in the reaction with
      the esters, provides further evidence that the MDH reaction mechanism is not a
      concerted transfer of a hydride ion from the substrate to the FMN, but involves
      the transient formation of a carbanion/ene(di)olate intermediate.

PMID- 14967030
TI  - Ligand-induced changes in estrogen receptor conformation as measured by site
      directed spin labeling.
AB  - Site-directed spin labeling (SDSL), the site-specific incorporation of nitroxide
      spin-labels into a protein, has allowed us to investigate ligand-induced
      conformational changes in the ligand-binding domain of human estrogen receptor
      alpha (hERalpha-LBD). EPR (electron paramagnetic resonance) spectroscopy of the
      nitroxide probe attached to ER produces different spectra depending upon the
      identity of the bound ligand; these differences are indicative of changes in the
      type and degree of motional character of the spin-label induced by different
      ligand-induced conformations of labeled ER. Visual inspection of EPR spectra,
      construction of B versus C cross-correlation plots, and cross-comparison of
      spectral pairs using a relative squared difference (RSD) calculation allowed
      receptor-ligand complexes to be profiled according to their conformational
      character. Plotting B and C parameters allowed us to evaluate the liganded
      receptor according to the motional characteristics of the attached spin-label,
      and they were particularly illustrative for the receptor labeled at position 530,
      which had motion between the fast and intermediate regimes. RSD analysis allowed
      us to directly compare the similarity or difference between two different
      spectra, and these comparisons produced groupings that paralleled those seen in B
      versus C cross-correlation plots, again relating meaningfully with the
      pharmacological nature of the bound ligand. RSD analysis was also particularly
      useful for qualifying differences seen with the receptor labeled at position 417,
      which had motion between the intermediate and slow motional regimes. This work
      demonstrates that B and C formulas from EPR line shape theory are useful for
      qualitative analysis of spectra with differences subtler than those that are
      often analyzed by EPR spectroscopists. This work also provides evidence that the
      ER can exist in a range of conformations, with specific conformations resulting
      from preferential stabilization of ER by the bound ligand. Furthermore, it
      documents the complexity and uniqueness of the ligand-receptor structure, and
      highlights the fact that structural differences exist between the receptor bound
      with ligands of different pharmacological character that, nevertheless, produce
      similar crystal structures.

PMID- 14967031
TI  - Probing cAMP-dependent protein kinase holoenzyme complexes I alpha and II beta by
      FT-IR and chemical protein footprinting.
AB  - Although individual structures of cAMP-dependent protein kinase (PKA) catalytic
      (C) and regulatory (R) subunits have been determined at the atomic level, our
      understanding of the effects of cAMP activation on protein dynamics and
      intersubunit communication of PKA holoenzymes is very limited. To delineate the
      mechanism of PKA activation and structural differences between type I and II PKA
      holoenzymes, the conformation and structural dynamics of PKA holoenzymes Ialpha
      and IIbeta were probed by amide hydrogen-deuterium exchange coupled with Fourier
      transform infrared spectroscopy (FT-IR) and chemical protein footprinting.
      Binding of cAMP to PKA holoenzymes Ialpha and IIbeta leads to a downshift in the
      wavenumber for both the alpha-helix and beta-strand bands, suggesting that R and
      C subunits become overall more dynamic in the holoenzyme complexes. This is
      consistent with the H-D exchange results showing a small change in the overall
      rate of exchange in response to the binding of cAMP to both PKA holoenzymes
      Ialpha and IIbeta. Despite the overall similarity, significant differences in the
      change of FT-IR spectra in response to the binding of cAMP were observed between
      PKA holoenzymes Ialpha and IIbeta. Activation of PKA holoenzyme Ialpha led to
      more conformational changes in beta-strand structures, while cAMP induced more
      apparent changes in the alpha-helical structures in PKA holoenzyme IIbeta.
      Chemical protein footprinting experiments revealed an extended docking surface
      for the R subunits on the C subunit. Although the overall subunit interfaces
      appeared to be similar for PKA holoenzymes Ialpha and IIbeta, a region around the
      active site cleft of the C subunit was more protected in PKA holoenzyme Ialpha
      than in PKA holoenzyme IIbeta. These results suggest that the C subunit assumes a
      more open conformation in PKA holoenzyme IIbeta. In addition, the chemical
      cleavage patterns around the active site cleft of the C subunit were distinctly
      different in PKA holoenzymes Ialpha and IIbeta even in the presence of cAMP.
      These observations provide direct evidence that the R subunits may be partially
      associated with the C subunit with the pseudosubstrate sequence docked in the
      active site cleft in the presence of cAMP.

PMID- 14967032
TI  - Efficient and isoform-selective inhibition of cellular gene expression by peptide
      nucleic acids.
AB  - Peptide nucleic acids (PNAs) are a potentially powerful approach for the
      recognition of cellular mRNA and the inhibition of gene expression. Despite their
      promise, the rules for using antisense PNAs have remained obscure, and antisense
      PNAs have been used sparingly in research. Here we investigate the ability of
      PNAs to be effective antisense agents inside mammalian cells, to inhibit
      expression of human caveolin-1 (hCav-1), and to discriminate between its alpha
      and beta isoforms. Many human genes are expressed as isoforms. Isoforms may play
      different roles within a cell or within different tissues, and defining these
      roles is a challenge for functional genomics and drug discovery. PNAs targeted to
      the translation start codons for the alpha and beta isoforms inhibit expression
      of hCav-1. Inhibition is dependent on PNA length. The potency and duration of
      inhibition by PNAs are similar to inhibition of gene expression by short
      interferring RNA (siRNA). Expression of the alpha isoform can be blocked
      selectively by a PNA. Cell proliferation is halted by inhibition of expression of
      both hCav-1 isoforms, but not by inhibition of the alpha hCav-1 isoform alone.
      Efficient antisense inhibition and selective modulation of isoform expression
      suggest that PNAs are versatile tools for controlling gene expression and
      dissecting the roles of closely related protein variants. Potent inhibition by
      PNAs may supply a "knock down" technology that can complement and "cross-check"
      siRNA and other approaches to antisense gene inhibition that rely on oligomers
      with phosphate or phosphorothioate backbone linkages.

PMID- 14967033
TI  - Mode of action for linear peptide inhibitors of HIV-1 gp120 interactions.
AB  - The linear peptide 12p1 (RINNIPWSEAMM) was previously isolated from a phage
      display library and was found to inhibit interaction of HIV-1 gp120 with both CD4
      and a CCR5 surrogate, mAb 17b [Ferrer, M., and Harrison, S. (1999) J. Virol. 73,
      5795-5802]. In this work, we investigated the mechanism that leads to this dual
      inhibition of gp120 binding. We found that there is a direct interaction of 12p1
      with gp120, which occurs with a binding stoichiometry of 1:1. The peptide
      inhibits binding of monomeric YU2 gp120 to both sCD4 and 17b at IC(50) values of
      1.1 and 1.6 microM, respectively. The 12p1 peptide also inhibited the binding of
      these ligands to trimeric envelope glycoproteins, blocked the binding of gp120 to
      the native coreceptor CCR5, and specifically inhibited HIV-1 infection of target
      cells in vitro. Analyses of sCD4 saturation of monomeric gp120 in the presence or
      absence of a fixed concentration of peptide suggest that 12p1 suppression of CD4
      binding to gp120 is due to allosteric inhibitory effects rather than competitive
      inhibition of CD4 binding. Using a panel of gp120 mutants that exhibit weakened
      inhibition by 12p1, the putative binding site of the peptide was mapped to a
      region immediately adjacent to, but distinguishable from, the CD4 binding
      footprint. In the case of the peptide, the effects of single-12p1 residue
      substitutions and various peptide truncations indicate that the side chain of
      Trp7 and other structural elements of 12p1 are critical for gp120 binding or
      efficient inhibition of binding of a ligand to gp120. Finally, 12p1 was unable to
      inhibit binding of sCD4 to a gp120 mutant that is believed to resemble the CD4
      induced conformation of gp120. These results suggest that 12p1 preferentially
      binds gp120 prior to engagement of CD4; binding of the peptide to gp120 limits
      the interaction with ligands (CD4 and CCR5) that are generally crucial for viral
      entry. More importantly, these results indicate that 12p1 binds to a unique site
      that may prove to be a prototypic target for novel CD4-gp120 inhibitors.

PMID- 14967034
TI  - A ratiometric expressible FRET sensor for phosphoinositides displays a signal
      change in highly dynamic membrane structures in fibroblasts.
AB  - Phosphoinositides are important signal transduction intermediates in cell growth,
      survival, and motility. We have invented a fluorescence sensor for
      polyphosphorylated phosphoinositides based on a peptide derived from the Listeria
      protein ActA that undergoes a random coil to helix transition upon lipid binding.
      The sensor, termed CAY, is a fusion protein of cyan and yellow fluorescent
      proteins flanking the peptide at its N- and C-termini, respectively. CAY displays
      fluorescence resonance energy transfer in vitro in the absence of phosphorylated
      phosphoinositides, and this energy transfer is lost upon interaction with these
      phospholipids. These results demonstrate that a short peptide undergoing a coil
      to helix transition can be sufficient for the engineering of a FRET-based
      biosensor. CAY is predominantly localized to the cytoplasm in fibroblasts
      expressing the sensor but shows loss of fluorescence resonance energy transfer in
      regions of active actin dynamics such as ruffles that have previously been
      demonstrated to contain high levels of phosphoinositides.

PMID- 14967035
TI  - Biophysical characterization of the complex between double-stranded RNA and the N
      terminal domain of the NS1 protein from influenza A virus: evidence for a novel
      RNA-binding mode.
AB  - The influenza virus nonstructural protein 1 encoded by influenza A virus (NS1A
      protein) is a multifunctional protein involved in both protein-protein and
      protein-RNA interactions. NS1A binds nonspecifically to double-stranded RNA
      (dsRNA) and to specific protein targets, and regulates several post
      transcriptional processes. The N-terminal structural domain corresponding to the
      first 73 amino acids of the NS1 protein from influenza A/Udorn/72 virus [NS1A(1
      73)] possesses all of the dsRNA binding activities of the full-length protein.
      Both NMR and X-ray crystallography of this domain have demonstrated that it is a
      symmetric homodimer which forms a six-helix chain fold, a unique structure that
      differs from that of the predominant class of dsRNA-binding domains, termed
      dsRBDs, that are found in a large number of eukaryotic and prokaryotic proteins.
      Here we describe biophysical experiments on complexes containing NS1A(1-73) and a
      short 16 bp synthetic dsRNA duplex. From sedimentation equilibrium measurements,
      we determined that the dimeric NS1A(1-73) binds to the dsRNA duplex with a 1:1
      stoichiometry, yielding a complex with an apparent dissociation constant (K(d))
      of approximately 1 microM. Circular dichroism and nuclear magnetic resonance
      (NMR) data demonstrate that the conformations of both NS1A(1-73) and dsRNA in the
      complex are similar to their free forms, indicating little or no structural
      change in the protein or RNA upon complex formation. NMR chemical shift
      perturbation experiments show that the dsRNA-binding epitope of NS1A(1-73) is
      associated with helices 2 and 2'. Analytical gel filtration and gel shift studies
      of the interaction between NS1A(1-73) and different double-stranded nucleic acids
      indicate that NS1A(1-73) recognizes canonical A-form dsRNA, but does not bind to
      dsDNA or dsRNA-DNA hybrids, which feature B-type or A/B-type intermediate
      conformations, respectively. On the basis of these results, we propose a three
      dimensional model of the complex in which NS1A(1-73) sits astride the minor
      groove of A-form RNA with a few amino acids in the helix 2-helix 2' face forming
      an electrostatically stabilized interaction with the phosphodiester backbone.
      This mode of dsRNA binding differs from that observed for any other dsRNA-binding
      protein.

PMID- 14967036
TI  - Role of active-site residues Thr81, Ser82, Thr85, Gln157, and Tyr158 in yeast
      cystathionine beta-synthase catalysis and reaction specificity.
AB  - Cystathionine beta-synthase (CBS) effects the condensation of l-serine with l
      homocysteine to form l-cystathionine. A series of active-site mutants, T81A,
      S82A, T85A, Q157A/E/H, and Y158F, was constructed to investigate effects on
      catalysis and reaction specificity in yeast CBS (yCBS). The effects of these
      mutations on the k(cat)/K(m)(L-Ser) for the beta-replacement reaction range from
      a reduction of only 3-fold for Y158F to below detectable levels for the Q157A and
      Q157E mutants. The order of importance of these residues to the beta-replacement
      reaction is Gln157 >or= Thr81 > Ser82 > Thr85 approximately Tyr158. All seven of
      the mutant enzymes catalyze a competing beta-elimination reaction, in which L-Ser
      is hydrolyzed to NH(3) and pyruvate. The ping-pong mechanism of CBS was thus
      expanded to include the latter reaction for these mutants. This activity is not
      detectable for wild-type yCBS, suggesting that the mutations result in a shift in
      the equilibrium between the open and the closed conformations of the active site
      of yCBS-substrate complexes. The Q157H and Y158F mutants additionally suffer
      suicide inhibition via a mechanism in which the released aminoacrylate
      intermediate covalently attacks the internal aldimine of the enzyme.

PMID- 14967037
TI  - Structural determinants for the intracellular degradation of human thymidylate
      synthase.
AB  - Thymidylate synthase (EC 2.1.1.45) (TS) catalyzes the conversion of dUMP to dTMP
      and is therefore indispensable for DNA replication in actively dividing cells.
      The enzyme is a critical target at which chemotherapeutic agents such as
      fluoropyrimidines (e.g., 5-fluorouracil and 5-fluoro-2'-deoxyuridine) and folic
      acid analogues (e.g., raltitrexed, LY231514, ZD9331, and BW1843U89) are directed.
      These agents exert their effects through the generation of metabolites that bind
      the active site of TS and inhibit catalytic activity. The binding of ligands to
      the TS molecule leads to dramatic changes in the conformation of the enzyme,
      particularly within the C-terminal domain. Stabilization of the enzyme and an
      increase in its intracellular level are associated with ligand binding and may be
      important in cellular response to TS-directed drugs. In the present study, we
      have examined molecular features of the TS molecule that control its degradation.
      We find that the C-terminal conformational shift is not required for ligand
      mediated stabilization of the enzyme. In addition, we demonstrate that the N
      terminus of the TS polypeptide, which is extended in the mammalian enzyme and is
      disordered in crystal structures, is a primary determinant of the enzyme's half
      life. Finally, we show that TS turnover is carried out by the 26S proteasome in a
      ubiquitin-independent manner. These findings provide the basis for a mechanistic
      understanding of TS degradation and its regulation by antimetabolites.

PMID- 14967038
TI  - Assignment of downfield proton resonances in purine nucleoside phosphorylase
      immucillin-H complex by saturation-transferred NOEs.
AB  - Purine nucleoside phosphorylase (PNP) catalyzes N-ribosidic bond phosphorolysis
      in 6-oxypurine nucleosides and deoxynucleosides to form purine and alpha-D
      phosphorylated ribosyl products. The transition state has oxacarbenium ion
      character with partial positive charge near C-1', ionic stabilization from the
      nearby phosphate anion, and protonation at N-7 of the purine. Immucillin-H (ImmH)
      has a protonated N-7 and resembles the transition-state charge distribution when
      N-4' is protonated to the cation. It binds tightly to the PNPs with a K(d) value
      56 pM for human PNP. Previous NMR studies of PNP. ImmH.PO(4) have shown that the
      N-4' of bound ImmH is a cation and is postulated to have a significant
      contribution to its tight binding. Several unassigned downfield proton resonances
      (>11 ppm) are specific to the PNP. ImmH.PO(4) complex, suggesting the existence
      of strong hydrogen bonds. In this study, two of the proton resonances in this
      downfield region have been assigned. Using (15)N-7-labeled ImmH, a resonance at
      12.5 ppm has been assigned to N-7H. The N-7H resonance is shifted downfield by
      only approximately 1 ppm from its position for ImmH free in aqueous solution,
      consistent with only a small change in the hydrogen bonding on N-7H upon binding
      of ImmH to PNP. In contrast, the downfield resonance at 14.9 ppm in the PNP.
      ImmH.PO(4) complex is assigned to N-1H of ImmH by using saturation-transferred
      NOE measurements on the PNP. ImmH complex. The approximately 4 ppm downfield
      shift of the N-1H resonance from its position for ImmH free in solution suggests
      that the hydrogen bonding to the N-1H in the complex has a significant
      contribution to the binding of ImmH to PNP. The crystal structure shows Glu201 is
      in a direct hydrogen bond with N-1H and to O-6 through a water bridge. In the
      complex with 6-thio-ImmH, the N-1H resonance is shifted further downfield by an
      additional 1.5 ppm to 16.4 ppm, but the relative shift from the value for 6-thio
      ImmH free in solution is the same as in the ImmH complex. Since the binding
      affinity to hPNP for 6-thio-ImmH is decreased 440-fold relative to that for ImmH,
      the loss in binding energy is primarily due to the hydrogen bond energy loss at
      the 6-thiol.

PMID- 14967039
TI  - Kinetic and thermodynamic characterization of the common polymorphic variants of
      human methionine synthase reductase.
AB  - Human methionine synthase reductase (MSR) is a protein containing both FAD and
      FMN, and it reactivates methionine synthase that has lost activity due to
      oxidation of cob(I)alamin to cob(II)alamin. In this study, anaerobic redox
      titrations were employed to determine the midpoint reduction potentials for the
      flavin cofactors in two highly prevalent polymorphic variants of MSR, I22/L175
      and M22/S175. The latter is a genetic determinant of plasma homocysteine levels
      and has been linked to premature coronary artery disease, Down's syndrome, and
      neural tube defects. The I22/L175 polymorphism has been described in a
      homocystinuric patient. Interestingly, this polymorphism is in the extended
      linker region between the two flavin domains, which may mediate or facilitate
      interaction with methionine synthase. In MSR I22/L175, the FMN potentials are 
      103 mV (oxidized/semiquinone) and -175 mV (semiquinone/hydroquinone) at pH 7.0
      and 25 degrees C, and the corresponding FAD potentials are -252 and -285 mV,
      respectively. For the M22/S175 variants, the values of the four midpoint
      potentials are -114 mV (FMN oxidized/semiquinone), -212 mV (FMN
      semiquinone/hydroquinone), -236 mV (FAD oxidized/semiquinone), and -264 mV (FAD
      semiquinone/hydroquinone). The midpoint potential values in the two variants are
      generally comparable to those originally determined for the MSR I22/S175 variant
      [Wolthers, K. R. (2003) Biochemistry 42, 3911-3920], with relatively minor
      variations in the different redox couples. In each case, blue neutral flavin
      semiquinone species are stabilized on both flavins, and are characterized by a
      broad absorption band in the long wavelength region. In addition, stopped-flow
      absorption and fluorescence spectroscopy were used to study the pre-steady state
      reduction kinetics by NADPH of the two polymorphic variants. The reversible
      kinetic model proposed for wild-type MSR was validated for the I22/L175 and
      M22/S175 variants. Thus, the biochemical penalties associated with these
      polymorphisms, which result in less effective methionine synthase activation, do
      not appear to result from differences in their reduction kinetics. It is likely
      that differences in their relative affinities for the redox partner, methionine
      synthase, underlie the differences in the relative efficiencies of reductive
      activation exhibited by the variants.

PMID- 14967040
TI  - Vibrationally enhanced hydrogen tunneling in the Escherichia coli thymidylate
      synthase catalyzed reaction.
AB  - The enzyme thymidylate synthase (TS) catalyzes a complex reaction that involves
      forming and breaking at least six covalent bonds. The physical nature of the
      hydride transfer step in this complex reaction cascade has been studied by means
      of isotope effects and their temperature dependence. Competitive kinetic isotope
      effects (KIEs) on the second-order rate constant (V/K) were measured over a
      temperature range of 5-45 degrees C. The observed H/T ((T)V/K(H)) and D/T
      ((T)V/K(D)) KIEs were used to calculate the intrinsic KIEs throughout the
      temperature range. The Swain-Schaad relationships between the H/T and D/T V/K
      KIEs revealed that the hydride transfer step is the rate-determining step at the
      physiological temperature of Escherichia coli (20-30 degrees C) but is only
      partly rate-determining at elevated and reduced temperatures. H/D KIE on the
      first-order rate constant k(cat) ((D)k = 3.72) has been previously reported
      [Spencer et al. (1997) Biochemistry 36, 4212-4222]. Additionally, the Swain
      Schaad relationships between that (D)k and the V/K KIEs reported here suggested
      that at 20 degrees C the hydride transfer step is the rate-determining step for
      both rate constants. Intrinsic KIEs were calculated here and were found to be
      virtually temperature independent (DeltaE(a) = 0 within experimental error). The
      isotope effects on the preexponential Arrhenius factors for the intrinsic KIEs
      were A(H)/A(T) = 6.8 +/- 2.8 and A(D)/A(T) = 1.9 +/- 0.25. Both effects are
      significantly above the semiclassical (no-tunneling) predicted values and
      indicate a contribution of quantum mechanical tunneling to this hydride transfer
      reaction. Tunneling correction to transition state theory would predict that
      these isotope effects on activation parameters result from no energy of
      activation for all isotopes. Yet, initial velocity measurements over the same
      temperature range indicate cofactor inhibition and result in significant
      activation energy on k(cat) (4.0 +/- 0.1 kcal/mol). Taken together, the
      temperature-independent KIEs, the large isotope effects on the preexponential
      Arrhenius factors, and a significant energy of activation all suggest
      vibrationally enhanced hydride tunneling in the TS-catalyzed reaction.

PMID- 14967041
TI  - Characterization of the cofactor composition of Escherichia coli biotin synthase.
AB  - The cofactor content of in vivo, as-isolated, and reconstituted forms of
      recombinant Escherichia coli biotin synthase (BioB) has been investigated using
      the combination of UV-visible absorption, resonance Raman, and Mossbauer
      spectroscopies along with parallel analytical and activity assays. In contrast to
      the recent report that E. coli BioB is a pyridoxal phosphate (PLP)-dependent
      enzyme with intrinsic cysteine desulfurase activity (Ollagnier-deChoudens, S.,
      Mulliez, E., Hewitson, K. S., and Fontecave, M. (2002) Biochemistry 41, 9145
      9152), no evidence for PLP binding or for PLP-induced cysteine desulfurase or
      biotin synthase activity was observed with any of the forms of BioB investigated
      in this work. The results confirm that BioB contains two distinct Fe-S cluster
      binding sites. One site accommodates a [2Fe-2S](2+) cluster with partial
      noncysteinyl ligation that can only be reconstituted in vitro in the presence of
      O(2). The other site accommodates a [4Fe-4S](2+,+) cluster that binds S
      adenosylmethionine (SAM) at a unique Fe site of the [4Fe-4S](2+) cluster and
      undergoes O(2)-induced degradation via a distinct type of [2Fe-2S](2+) cluster
      intermediate. In vivo Mossbauer studies show that recombinant BioB in
      anaerobically grown cells is expressed exclusively in an inactive form containing
      only the as-isolated [2Fe-2S](2+) cluster and demonstrate that the [2Fe-2S](2+)
      cluster is not a consequence of overexpressing the recombinant enzyme under
      aerobic growth conditions. Overall the results clarify the confusion in the
      literature concerning the Fe-S cluster composition and the in vitro
      reconstitution and O(2)-induced cluster transformations that are possible for
      recombinant BioB. In addition, they provide a firm foundation for assessing
      cluster transformations that occur during turnover and the catalytic competence
      of the [2Fe-2S](2+) cluster as the immediate S-donor for biotin biosynthesis.

PMID- 14967042
TI  - Role of the [2Fe-2S] cluster in recombinant Escherichia coli biotin synthase.
AB  - Biotin synthase (BioB) converts dethiobiotin into biotin by inserting a sulfur
      atom between C6 and C9 of dethiobiotin in an S-adenosylmethionine (SAM)-dependent
      reaction. The as-purified recombinant BioB from Escherichia coli is a homodimeric
      molecule containing one [2Fe-2S](2+) cluster per monomer. It is inactive in vitro
      without the addition of exogenous Fe. Anaerobic reconstitution of the as-purified
      [2Fe-2S]-containing BioB with Fe(2+) and S(2)(-) produces a form of BioB that
      contains approximately one [2Fe-2S](2+) and one [4Fe-4S](2+) cluster per monomer
      ([2Fe-2S]/[4Fe-4S] BioB). In the absence of added Fe, the [2Fe-2S]/[4Fe-4S] BioB
      is active and can produce up to approximately 0.7 equiv of biotin per monomer. To
      better define the roles of the Fe-S clusters in the BioB reaction, Mossbauer and
      electron paramagnetic resonance (EPR) spectroscopy have been used to monitor the
      states of the Fe-S clusters during the conversion of dethiobiotin to biotin. The
      results show that the [4Fe-4S](2+) cluster is stable during the reaction and
      present in the SAM-bound form, supporting the current consensus that the
      functional role of the [4Fe-4S] cluster is to bind SAM and facilitate the
      reductive cleavage of SAM to generate the catalytically essential 5'
      deoxyadenosyl radical. The results also demonstrate that approximately (2)/(3) of
      the [2Fe-2S] clusters are degraded by the end of the turnover experiment (24 h at
      25 degrees C). A transient species with spectroscopic properties consistent with
      a [2Fe-2S](+) cluster is observed during turnover, suggesting that the
      degradation of the [2Fe-2S](2+) cluster is initiated by reduction of the cluster.
      This observed degradation of the [2Fe-2S] cluster during biotin formation is
      consistent with the proposed sacrificial S-donating function of the [2Fe-2S]
      cluster put forth by Jarrett and co-workers (Ugulava et al. (2001) Biochemistry
      40, 8352-8358). Interestingly, degradation of the [2Fe-2S](2+) cluster was found
      not to parallel biotin formation. The initial decay rate of the [2Fe-2S](2+)
      cluster is about 1 order of magnitude faster than the initial formation rate of
      biotin, indicating that if the [2Fe-2S] cluster is the immediate S donor for
      biotin synthesis, insertion of S into dethiobiotin would not be the rate-limiting
      step. Alternatively, the [2Fe-2S] cluster may not be the immediate S donor.
      Instead, degradation of the [2Fe-2S] cluster may generate a protein-bound
      polysulfide or persulfide that serves as the immediate S donor for biotin
      production.

PMID- 14967043
TI  - The peptidyl prolyl cis/trans-isomerase Pin1 recognizes the phospho-Thr212-Pro213
      site on Tau.
AB  - The interaction between the neuronal Tau protein and the Pin1 prolyl cis/trans
      isomerase is dependent on the phosphorylation state of the former. The
      interaction site was mapped to the unique phospho-Thr231-Pro232 motif, despite
      the presence of many other Thr/Ser-Pro phosphorylation sites in Tau and
      structural evidence that the interaction site does not significantly extend
      beyond those very two residues. We demonstrate here by NMR and fluorescence
      mapping that the Alzheimer's disease specific epitope centered around the phospho
      Thr212-Pro213 motif is also an interaction site, and that the sole phospho-Thr
      Pro motif is already sufficient for interaction. Because a detectable fraction of
      the Pro213 amide bond in the peptide centered around the phospho-Thr212-Pro213
      motif is in the cis conformation, catalysis of the isomerization by the catalytic
      domain of Pin1 could be investigated via NMR spectroscopy.

PMID- 14967044
TI  - Analysis of the antigen binding site of anti-deoxycholate monoclonal antibody
      using a novel affinity labeling reagent, acyl adenylate.
AB  - Large-scale analysis of protein-protein interaction sites is especially needed in
      the postgenomic era. The combination of affinity labeling with mass spectrometry
      is a potentially useful high-throughput screening method for this purpose.
      However, reagents in current use are not ideal as some cause damage to the target
      molecule and others have poor solubility in physiologic aqueous buffers. In this
      paper, we describe a novel affinity labeling reagent, acyl adenylate, which is
      highly soluble in aqueous solutions and reacts in a pH-dependent manner. The
      adenylate of deoxycholic acid reacts with amino groups on the side chain of a
      lysine residue and at the N-terminus of proteins/peptides. The reactivity and
      stability of this reagent were investigated, and it was confirmed that, after
      formation of a reversible ligand-protein complex under weakly acidic conditions,
      derivatization with acyl adenylate occurred at the target site under weakly
      alkaline condition. We further demonstrated the utility of this reagent for
      affinity labeling using a monoclonal antibody with high affinity for deoxycholic
      acid. Competitive ELISA indicated that deoxycholic acid was labeled around the
      antibody ligand binding site, thus enabling the structural elucidation of the
      ligand-protein interaction. In addition, LC/ESI-MS/MS analysis of the labeled
      peptide obtained by enzymatic digestion and affinity extraction allowed the
      identification of the structure surrounding the antigen binding site.

PMID- 14967045
TI  - Homooligomerization of the cytoplasmic domain of the T cell receptor zeta chain
      and of other proteins containing the immunoreceptor tyrosine-based activation
      motif.
AB  - Antigen receptors on T cells, B cells, mast cells, and basophils all have
      cytoplasmic domains containing one or more copies of an immunoreceptor tyrosine
      based activation motif (ITAM), tyrosine residues of which are phosphorylated upon
      receptor engagement in an early and obligatory event in the signaling cascade.
      How clustering of receptor extracellular domains leads to phosphorylation of
      cytoplasmic domain ITAMs is not known, and little structural or biochemical
      information is available for the ITAM-containing cytoplasmic domains. Here we
      investigate the conformation and oligomeric state of several immune receptor
      cytoplasmic domains, using purified recombinant proteins and a variety of
      biophysical and biochemical techniques. We show that all of the cytoplasmic
      domains of ITAM-containing signaling subunits studied are oligomeric in solution,
      namely, T cell antigen receptor zeta, CD3epsilon, CD3delta, and CD3gamma, B cell
      antigen receptor Igalpha and Igbeta, and Fc receptor FcepsilonRIgamma. For
      zeta(cyt), the oligomerization behavior is best described by a two-step monomer
      dimer-tetramer fast dynamic equilibrium with dissociation constants in the order
      of approximately 10 microM (monomer-dimer) and approximately 1 mM (dimer
      tetramer). In contrast to the other ITAM-containing proteins, Igalpha(cyt) forms
      stable dimers and tetramers even below 10 microM. Circular dichroic analysis
      reveals the lack of stable ordered structure of the cytoplasmic domains studied,
      and oligomerization does not change the random-coil-like conformation observed.
      The random-coil nature of zeta(cyt) was also confirmed by heteronuclear NMR.
      Phosphorylation of zeta(cyt) and FcepsilonRIgamma(cyt) does not significantly
      alter their oligomerization behavior. The implications of these results for
      transmembrane signaling and cellular activation by immune receptors are
      discussed.

PMID- 14967046
TI  - Quantitative analysis of the interaction between the fluorescent probe eosin and
      the Na+/K+-ATPase studied through Rb+ occlusion.
AB  - We report a study on the effect of the fluorescent probe eosin on some of the
      reactions involved in the conformational transitions that lead to the occlusion
      of the K(+)-congener Rb(+) in the Na(+)/K(+)-ATPase. Eosin decreases the
      equilibrium levels of occluded Rb(+), this effect being fully attributable to a
      decrease in the apparent affinity of the enzyme for Rb(+) since the capacity for
      occlusion remains independent of eosin concentration. The results can be
      quantitatively described by a model that assumes that two molecules of eosin are
      able to bind to the Na(+)/K(+)-ATPase, both to the Rb(+)-free and to the Rb(+)
      occluded enzyme regardless of the degree of cation occlusion. Concerning the
      effect on the affinity for Rb(+) occlusion, transient state experiments show that
      eosin reduces the initial velocity of occlusion, and that, like ATP, it increases
      the velocity of deocclusion of Rb(+). Interactions between eosin and ATP on Rb(+)
      release experiments seem to indicate that eosin binds to the low-affinity site of
      ATP from which it exerts effects that are similar to those of the nucleotide.

PMID- 14967047
TI  - Bicarbonate is a native cofactor for assembly of the manganese cluster of the
      photosynthetic water oxidizing complex. Kinetics of reconstitution of O2
      evolution by photoactivation.
AB  - Assembly of the inorganic core (Mn(4)O(x)Ca(1)Cl(y)) of the water oxidizing
      enzyme of oxygenic photosynthesis generates O(2) evolution capacity via the
      photodriven binding and photooxidation of the free inorganic cofactors within the
      cofactor-depleted enzyme (apo-WOC-PSII) by a process called photoactivation.
      Using in vitro photoactivation of spinach PSII membranes, we identify a new lower
      affinity site for bicarbonate interaction in the WOC. Bicarbonate addition causes
      a 300% stimulation of the rate and a 50% increase in yield of photoassembled PSII
      centers when using Mn(2+) and Ca(2+) concentrations that are 10-50-fold larger
      range than previously examined. Maintenance of a fixed Mn(2+)/Ca(2+) ratio
      (1:500) produces the fastest rates and highest yields of photoactivation, which
      has implications for intracellular cofactor homeostasis. A two-step
      (biexponential) model is shown to accurately fit the assembly kinetics over a 200
      fold range of Mn(2+) concentrations. The first step, the binding and
      photooxidation of Mn(2+) to Mn(3+), is specifically stimulated via formation of a
      ternary complex between Mn(2+), bicarbonate, and apo-WOC-PSII, having a proposed
      stoichiometry of [Mn(2+)(HCO(3)(-))]. This low-affinity bicarbonate complex is
      thermodynamically easier to oxidize than the aqua precursor, [Mn(2+)(OH(2))]. The
      photooxidized intermediate, [Mn(3+)(HCO(3)(-))], is longer lived and increases
      the photoactivation yield by suppressing irreversible photodamage to the cofactor
      free apo-WOC-PSII (photoinhibition). Bicarbonate does not affect the second (rate
      limiting) dark step of photoactivation, attributed to a protein conformational
      change. Together with the previously characterized high-affinity site, these
      results reveal that bicarbonate is a multifunctional "native" cofactor important
      for photoactivation and photoprotection of the WOC-PSII complex.

PMID- 14967048
TI  - Phosphatidylinositol-specific phospholipase C forms different complexes with
      monodisperse and micellar phosphatidylcholine.
AB  - Phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus cereus forms
      a premicellar complex E(#) with monodisperse diheptanoylphosphatidylcholine
      (DC(7)PC) that is distinguishable from the E complex formed with micelles.
      Results are interpreted with the assumption that in both cases amphiphiles bind
      to the interfacial binding surface (i-face) of PI-PLC but not to the active site.
      Isothermal calorimetry and fluorescence titration results for the binding of
      monodisperse DC(7)PC give an apparent dissociation constant of K(2) = 0.2 mM with
      Hill coefficient of 2. The gel-permeation, spectroscopic, and probe partitioning
      behaviors of E(#) are distinct from those of the E complex. The aggregation and
      partitioning behaviors suggest that the acyl chains in E(#) but not in E remain
      exposed to the aqueous phase. The free (E) and complexed (E(#) and E) forms of PI
      PLC, each with distinct spectroscopic signatures, readily equilibrate with
      changing DC(7)PC concentration. The underlying equilibria are modeled and their
      significance for the states of the PI-PLC under monomer kinetic conditions is
      discussed to suggest that the Michaelis-Menten complex formed with monodisperse
      DC(7)PC is likely to be E(#)S or its aggregate rather than the classical
      monodisperse ES complex.

PMID- 14967049
TI  - Identification of endogenous phosphorylation sites of bovine medium and low
      molecular weight neurofilament proteins by tandem mass spectrometry.
AB  - Neurofilament proteins (NFP) are intermediate filaments found in the neuronal
      cytoskeleton. They are highly phosphorylated, a condition that is believed to be
      responsible for the assembly and stability of the filaments. Matrix-assisted
      laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS)
      shows molecular masses for bovine NFP subunits of 63, 105, and 125 kDa for NFL,
      NFM, and NFH. Mass spectrometric de novo sequencing was used to determine the N
      terminal sequence of bovine NFM (115 amino acids), which was previously unknown.
      Molecular mass information shows that there is one-half equivalent phosphate
      group on NFL and 24 on NFM. For the first time, it is shown that bovine NFL has
      three phosphorylation sites (Ser(55), Ser(66), and Ser(472)) and NFM has 22
      (Ser(512), Ser(546), Ser(554), Ser(560), Thr(627), Ser(629), Ser(634), Ser(639),
      Thr(646), Ser(649), Ser(654), Ser(664), Ser(669), Thr(676), Ser(679), Ser(684),
      Ser(694), Ser(726), Ser(750), Ser(756), Ser(770), and Ser(846)) and two tentative
      sites (Ser(659)/Thr(661) and Thr(840)). Ser(66) was previously not known to be
      phosphorylated in NFL of other species, while two sites (Ser(55) and Ser(472))
      are consistent with the phosphorylations observed in other mammalian NFLs. The
      three sites, Ser(55), Ser(66), Ser(472), are heterogeneously phosphorylated.
      Phosphorylation in bovine NFM occurs mainly in the Lys-Ser-Pro (KSP) region, but
      the Val-Ser-Pro and Ser-Glu-Lys motifs are also phosphorylated. Most of the
      phosphorylation sites are in accordance with those previously identified in other
      mammalian NFMs. In bovine NFM, 16 out of the 22 sites are always phosphorylated
      (Ser(512), Thr(627), Ser(629), Ser(634), Ser(639), Thr(646), Ser(649), Ser(654),
      Ser(664), Ser(669), Thr(676), Ser(679), Ser(684), Ser(694), Ser(726), and
      Ser(750)), all of which are contained in the KSP region, and six are sometimes
      phosphorylated (Ser(546), Ser(554), Ser(560), Ser(756), Ser(770), and Ser(846)).
      The NFPs have other modifications, including deamidation, oxidation, and N
      terminal acetylation. Pyroglutamic acid formation also occurs.

PMID- 14967050
TI  - Pre-steady-state kinetic studies of the fidelity of Sulfolobus solfataricus P2
      DNA polymerase IV.
AB  - Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4) is a thermostable archaeal
      enzyme and a member of the error-prone and lesion-bypass Y-family. In this paper,
      for the first time, the fidelity of a Y-family polymerase, Dpo4, was determined
      using pre-steady-state kinetic analysis of the incorporation of a single
      nucleotide into an undamaged DNA substrate 21/41-mer at 37 degrees C. We assessed
      single-turnover (with Dpo4 in molar excess over DNA) saturation kinetics for all
      16 possible nucleotide incorporations. The fidelity of Dpo4 was estimated to be
      in the range of 10(-3)-10(-4). Interestingly, the ground-state binding affinity
      of correct nucleotides (70-230 microM) is 10-50-fold weaker than those of
      replicative DNA polymerases. Such a low affinity is consistent with the lack of
      interactions between Dpo4 and the bound nucleotides as revealed in the crystal
      structure of Dpo4, DNA, and a matched nucleotide. The affinity of incorrect
      nucleotides for Dpo4 is approximately 2-10-fold weaker than that of correct
      nucleotides. Intriguingly, the mismatched dCTP has an affinity similar to that of
      the matched nucleotides when it is incorporated against a pyrimidine template
      base flanked by a 5'-template guanine. The incoming dCTP likely skips the first
      available template base and base pairs with the 5'-template guanine, as observed
      in the crystal structure of Dpo4, DNA, and a mismatched nucleotide. The mismatch
      incorporation rates, regardless of the 5'-template base, were approximately 2-3
      orders of magnitude slower than the incorporation rates for matched nucleotides,
      which is the predominant contribution to the fidelity of Dpo4.

PMID- 14967051
TI  - Mechanism of DNA polymerization catalyzed by Sulfolobus solfataricus P2 DNA
      polymerase IV.
AB  - The kinetic mechanism of DNA polymerization catalyzed by Sulfolobus solfataricus
      P2 DNA polymerase IV (Dpo4) is resolved by pre-steady-state kinetic analysis of
      single-nucleotide (dTTP) incorporation into a DNA 21/41-mer. Like replicative DNA
      polymerases, Dpo4 utilizes an "induced-fit" mechanism to select correct incoming
      nucleotides. The affinity of DNA and a matched incoming nucleotide for Dpo4 was
      measured to be 10.6 nM and 230 microM, respectively. Dpo4 binds DNA with an
      affinity similar to that of replicative polymerases due to the presence of an
      atypical little finger domain and a highly charged tether that links this novel
      domain to its small thumb domain. On the basis of the elemental effect between
      the incorporations of dTTP and its thio analogue S(p)-dTTPalphaS, the
      incorporation of a correct incoming nucleotide by Dpo4 was shown to be limited by
      the protein conformational change step preceding the chemistry step. In contrast,
      the chemistry step limited the incorporation of an incorrect nucleotide. The
      measured dissociation rates of the enzyme.DNA binary complex (0.02-0.07 s(-1)),
      the enzyme.DNA.dNTP ternary complex (0.41 s(-1)), and the ternary complex after
      the protein conformational change (0.004 s(-1)) are significantly different and
      support the existence of a bona fide protein conformational change step. The rate
      limiting protein conformational change was further substantiated by the
      observation of different reaction amplitudes between pulse-quench and pulse-chase
      experiments. Additionally, the processivity of Dpo4 was calculated to be 16 at 37
      degrees C from analysis of a processive polymerization experiment. The structural
      basis for both the protein conformational change and the low processivity of Dpo4
      was discussed.

PMID- 14967052
TI  - Cross-linking and lipid efflux properties of apoA-I mutants suggest direct
      association between apoA-I helices and ABCA1.
AB  - To explore the functional interactions between apoA-I and ABCA1, we correlated
      the cross-linking properties of several apoA-I mutants with their ability to
      promote cholesterol efflux. In a competitive cross-linking assay, amino-terminal
      deletion and double amino- and carboxy-terminal deletion mutants of apoA-I
      competed effectively the cross-linking of WT (125)I-apoA-I to ABCA1, while the
      carboxy-terminal deletion mutant apoA-I[Delta(220-243)] competed poorly. Direct
      cross-linking of WT apoA-I, amino-terminal, and double deletion mutants of apoA-I
      to ABCA1 showed similar apparent K(d) values (49-74 nM), whereas the apparent
      K(d) values of the carboxy-terminal deletion mutants apoA-I[Delta(185-243)] and
      apoA-I[Delta(220-243)] were increased 3-fold. Analysis of several internal
      deletions and point mutants of apoA-I showed that apoA-I[Delta(61-78)], apoA
      I[Delta(89-99)], apoA-I[Delta(136-143)], apoA-I[Delta(144-165)], apoA
      I[D102A/D103A], apoA-I[E125K/E128K/K133E/E139K], apoA-I[L141R], apoA
      I[R160V/H162A], and WT apoA-I had similar ABCA1-mediated lipid efflux, and all
      competed efficiently the cross-linking of WT (125)I-apoA-I to ABCA1. WT apoA-I
      and ABCA1 could be cross-linked with a 3 A cross-linker. The WT apoA-I, amino,
      carboxy and double deletion mutants of apoA-I showed differences in the cross
      linking to WT ABCA1 and the mutant ABCA1[W590S]. The findings are consistent with
      a direct association of different combinations of apoA-I helices with a
      complementary ABCA1 domain. Mutations that alter ABCA1/apoA-I association affect
      cholesterol efflux and inhibit biogenesis of HDL.

PMID- 14967054
TI  - Copper binding in the prion protein.
AB  - A conformational change of the prion protein is responsible for a class of
      neurodegenerative diseases called the transmissible spongiform encephalopathies
      that include mad cow disease and the human afflictions kuru and Creutzfeldt-Jakob
      disease. Despite the attention given to these diseases, the normal function of
      the prion protein in healthy tissue is unknown. Research over the past few years,
      however, demonstrates that the prion protein is a copper binding protein with
      high selectivity for Cu(2+). The structural features of the Cu(2+) binding sites
      have now been characterized and are providing important clues about the normal
      function of the prion protein and perhaps how metals or loss of protein function
      play a role in disease. The link between prion protein and copper may provide
      insight into the general, and recently appreciated, role of metals in
      neurodegenerative disease.

PMID- 14967055
TI  - New progress in the chemistry of stable metallaaromatic compounds of heavier
      group 14 elements.
AB  - By taking advantage of kinetic stabilization afforded by introduction of an
      efficient steric protection group, several kinds of silaaromatic compounds, such
      as silabenzene, 1- and 2-silanaphthalenes, and 9-silaanthracene, were
      successfully synthesized and isolated as stable compounds. The first stable
      germaaromatics, such as germabenzene and 2-germanaphthalene, were also
      synthesized by the use of a similar synthetic approach. Most of their molecular
      structures were definitively determined by X-ray crystallographic analysis. The
      novel molecular structures and unique reactivities of these metallaaromatic
      species are discussed on the basis of the experimental results together with
      those obtained by theoretical calculations, focusing on their aromaticity.

PMID- 14967056
TI  - Laser-assisted high-pressure chemical reactions.
AB  - The growing need for production methods with a reduced environmental impact
      drives the search for new synthetic approaches in chemistry. Here we report the
      state of the art of a recently developed branch of ultra-high-pressure chemistry,
      employing high pressure to create the necessary reaction conditions to transform
      simple hydrocarbons and monochromatic light to trigger and direct, according to
      selective paths, the chemical reaction. For the available systems studied up to
      now, we will provide an overview of the different effects that can be obtained by
      the combined use of pressure and laser light.

PMID- 14967057
TI  - The direct catalytic asymmetric mannich reaction.
AB  - The direct catalytic asymmetric addition of unmodified carbonyl compounds to
      preformed or in situ-generated imines has emerged as a promising new route to
      optically enriched alpha- and beta-amino acid derivatives, beta-lactams, and 1,2-
      and gamma-amino alcohols. The direct catalytic asymmetric Mannich reactions are
      mediated by small organometallic and organic amine catalysts that can achieve
      levels of selectivity similar to those possible with natural enzymes. The
      different small-molecule catalysts described here are complementary in their
      applications. They also complement each other in syn or anti selectivity of the
      direct asymmetric Mannich reaction. In this Account, we highlight the recent
      developments in and contributions to this research.

PMID- 14967058
TI  - Effective molarities in supramolecular catalysis of two-substrate reactions.
AB  - Reactivity data related to processes in which molecular receptors promote the
      reaction of two simultaneously complexed reactants have been surveyed and
      analyzed in terms of effective molarity (EM). Methods and criteria for the
      calculation of reliable EM's have been highlighted. Extension of a previous
      extrathermodynamic treatment of intramolecular reactions of bifunctional chains
      to the intracomplex reactions of the ternary complexes involved in two-substrate
      catalyzed reactions has provided a sound framework for a comparative analysis of
      reactivity and catalytic efficiency in structurally diverse and apparently
      unrelated systems.

PMID- 14967059
TI  - Loops, linkages, rings, catenanes, cages, and crowders: entropy-based strategies
      for stabilizing proteins.
AB  - A protein molecule exists in either a compact folded state or a variable and open
      unfolded state. Since the unfolded state is favored by chain entropy, restricting
      its entropy is an attractive mechanism for shifting the equilibrium toward the
      folded state. A number of entropy-based strategies have been engineered or used
      by natural proteins to increase the folding stability: (a) shortening of loop
      lengths, (b) covalent linkage of dimeric proteins, (c) backbone cyclization, (d)
      catenation, (e) spatial confinement, and (f) macromolecular crowding. Theoretical
      analyses demonstrate the importance of accounting for consequences on the folded
      as well as the unfolded state and provide guidance for further exploitation of
      these stabilization strategies.

PMID- 14967060
TI  - Tyrosine-derived quinone cofactors.
AB  - Copper amine oxidases (CAOs) and lysyl oxidase (LOX) both contain Cu(2+) and
      quinone cofactors that are derived from a tyrosine residue in the active site. In
      CAOs, the cofactor is 2,4,5-trihydroxyphenylalanine quinone (TPQ), and in LOX it
      is lysine tyrosyl quinone (LTQ). The mechanism of oxidative deamination by CAOs
      is well understood, but there is a controversy surrounding the role of Cu(2+) in
      cofactor reoxidation. The chemistry of LTQ in LOX, by contrast, has not been as
      extensively studied. This Account discusses the strategies that CAOs have evolved
      to control the mobility of TPQ to optimize activity. In addition, some recent
      studies on CAOs whose active-site Cu(2+) has been replaced with Co(2+) or Ni(2+)
      are summarized. Finally, there is a discussion on the properties of a model
      compound of LTQ and their relevance to the chemistry of LOX.

PMID- 14967061
TI  - A perspective on the toxicological mechanisms possibly contributing to the
      failure of oral glycoprotein IIb/IIIa antagonists in the clinic.
AB  - In clinical trials in patients with acute or unstable coronary syndromes and/or
      undergoing percutaneous coronary intervention, oral glycoprotein (GP) IIb/IIIa
      antagonists did not show therapeutic benefit over aspirin during long-term
      administration. Moreover, high-dose oral administration of these agents was
      associated with greater fatality risk compared with that of lower doses. This
      article postulates that continuous exposure of the GP IIb/IIIa receptor (integrin
      alpha(IIb)beta(3)) to these agents may result in some form of resistance or
      activation of other biological systems. These toxicological mechanisms may help
      explain some factors that could potentially contribute to the failure of these
      agents in clinical trials. Several hypotheses are presented: (i) modulation of
      platelet response because of long-term exposure to GP IIb/IIIa antagonists; (ii)
      role of related integrins and associated proteins to compensate for the loss of
      platelet activity because of dysfunctional GP IIb/IIIa receptors occupied by
      inhibitors; (iii) effects of the GP IIb/IIIa antagonists on other cellular
      systems such as the caspase and procaspase enzymes in apoptosis and possibly the
      ryanodine receptor involved in sarcoplasmic reticulum calcium release. These
      toxicological mechanisms could potentially limit the utility of these oral agents
      in long-term administration.

PMID- 14967062
TI  - Is there any future for tumor necrosis factor antagonists in chronic heart
      failure?
AB  - Over the past decade, a large number of studies have demonstrated that tumor
      necrosis factor-alpha (TNFalpha) plays an important role in the development of
      heart failure. Indeed, administration of TNFalpha to experimental animals and
      transgenic over-expression of TNFalpha replicate the heart failure phenotype.
      Furthermore, attenuation of the biologic activity of TNFalpha abrogates the
      development of heart failure in model systems. These pre-clinical studies,
      suggested that anti-cytokine therapy could prove beneficial in the treatment of
      patients with heart failure. While early studies supported this hypothesis, anti
      TNF strategies have not demonstrated salutary benefits in large, multicenter
      randomized and placebo-controlled clinical trials in patients with symptomatic
      heart failure. This finding was disappointing. However, recent studies might
      provide clarification of this conundrum. For example, the failure to elicit
      beneficial effects with anti-cytokine therapy might be explained by novel
      pharmacogenomic or pharmacodynamic effects, the design of the Phase III clinical
      trials, or discordance between animal models and the human condition. Thus,
      appropriately designed clinical trials and newer anticytokine agents may
      demonstrate benefit.

PMID- 14967063
TI  - Calcineurin inhibitor-associated early renal insufficiency in cardiac transplant
      recipients: risk factors and strategies for prevention and treatment.
AB  - Cardiac transplantation is the definitive treatment for eligible patients with
      end-stage cardiac failure. Techniques have evolved to reduce surgical mortality
      to under 5%. Immediate and subsequent long-term survival is more dependent on
      acute and chronic rejection and the complications of immunosuppressive therapy.
      Ten-year survival is greater than 50%.The success of transplantation over the
      last 20 years has been largely due to the advances in immunosuppression. The most
      notable and dramatic milestone was the introduction of cyclosporine in the early
      1980s, which resulted in a significant improvement in allograft and patient
      survival. Cyclosporine is a peptide that inhibits the immune system by
      suppressing T-helper cell activation via inhibition of calcineurin, a critical
      intracellular enzyme. Tacrolimus has a similar (but not identical) mechanism of
      action, and was introduced in the 1990s. Drugs such as cyclosporine and
      tacrolimus, generically referred to as calcineurin inhibitors, have become the
      cornerstones of immunosuppressive protocols. As a group, calcineurin inhibitors
      have adverse effects, including neurotoxicity, hypertension, and nephrotoxicity,
      which complicate their use. Early renal insufficiency manifests as postoperative
      oliguria (<50 mL/h urine output) or rising serum creatinine levels. There are a
      variety of postulated causes for calcineurin inhibitor-associated early renal
      insufficiency including direct calcineurin inhibitor-mediated renal arteriolar
      vasoconstriction, increased levels of endothelin-1 (a potent vasoconstrictor), as
      well as decreased nitric oxide production and alterations in the kidney's ability
      to adjust to changes in serum tonicity. Once early renal insufficiency occurs, no
      single treatment has been shown to be effective. Approaches discussed in this
      paper include reduction in calcineurin inhibitor dosages, as well as various
      drugs to promote increased renal perfusion such as misoprostol and dopamine. In
      addition, the paper emphasizes the importance of ruling out other causes of renal
      insufficiency in the early postoperative period, including volume depletion,
      depressed cardiac output, and mechanical obstruction to urine flow. Given that
      there is no highly efficacious treatment for this syndrome, ways to avoid its
      occurrence are desirable. One paper is referenced that suggests that avoidance of
      rapid changes in tacrolimus level during the first three days of therapy is
      associated with a low occurrence of early renal insufficiency.

PMID- 14967064
TI  - Therapeutic use of intravenous eptifibatide in patients undergoing percutaneous
      coronary intervention: acute coronary syndromes and elective stenting.
AB  - Eptifibatide, a molecule isolated from the venom of the southeastern pygmy
      rattlesnake, selectively inhibits the platelet receptor IIb/IIIa. The safety and
      clinical efficacy of eptifibatide in patients undergoing percutaneous coronary
      intervention (PCI) was first evaluated in the Integrilin to Minimize Platelet
      Aggregation and Coronary Thrombosis (IMPACT) trial. In this study, the primary
      combined endpoint (composite of death, myocardial infarction [MI] or target
      vessel revascularization [TVR] at 30 days) occurred in 9.6% of the patients
      assigned to eptifibatide bolus followed by the 4-hour infusion versus 12.2% in
      the placebo group (p = 0.67). In the IMPACT-II trial, two different eptifibatide
      dosages were studied in 4011 patients undergoing elective PCI. The primary
      endpoint (death, MI, TVR or stent placement for threatened vessel closure at 30
      days) occurred in 11.6% in the placebo group versus 9.1% in the 135/0.5
      eptifibatide group (p = 0.035) and 10% in the 135/0.75 eptifibatide group (p =
      0.18). The Enhanced Suppression of Platelet IIb/IIIa Receptor with Integrilin
      Therapy (ESPRIT) trial studied a dose of eptifibatide 3- to 4-fold higher than
      that used in IMPACT II trial in patients undergoing non-emergent coronary artery
      stenting (two 180 microg/kg bolus doses 10 minutes apart). The 6-month composite
      endpoint (death, MI, TVR and 'bailout' eptifibatide use) occurred in 18.3% of
      patients in the placebo group versus 14.2% in the eptifibatide group (p = 0.008)
      and was maintained at 12 months (22.1% in the placebo group vs 17.5% in the
      eptifibatide group, p = 0.0068). The Platelet Glycoprotein IIb/IIIa in Unstable
      Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) study in 10 948
      patients was designed to study the effect of eptifibatide in the treatment of
      acute coronary syndromes (ACS) using two different dosages (180 microg/kg bolus
      followed by an infusion of either 1.3 microg/kg/min or 2 microg/kg/min. The
      primary endpoint, a composite of death or MI at 30 days, occurred in 15.7% of
      placebo-treated patients and 14.2% of eptifibatide-treated patients (p = 0.042).
      This difference was maintained at 7 days (11.6% in the placebo group vs 10.1% in
      the eptifibatide group, p = 0.016) and at 30 days (15.7% in the placebo group vs
      14.2% in the eptifibatide group). In the eptifibatide studies, the rates of major
      bleeding were 0.7% (0.5% in the control group) in ESPRIT and 2.1% (1.3% in the
      placebo group) in PURSUIT. The incidence of intracranial bleeding was 0.2% in
      ESPRIT (0.1% in the placebo group) and 0.7% in PURSUIT (0.8% in the placebo
      group). Significant thrombocytopenia (platelet count <20 000/microL) was reported
      in 0.2% of the patients receiving eptifibatide in the ESPRIT trial (0% in the
      placebo group) and in <1% in PURSUIT (<1% in the placebo group). In summary,
      several clinical trials have demonstrated a clear-cut reduction in a variety of
      ischemic events in patients receiving eptifibatide as adjunctive pharmacotherapy
      during PCI.

PMID- 14967065
TI  - The use of vitamin K in patients on anticoagulant therapy: a practical guide.
AB  - Anticoagulation with antivitamin K (AVK) is very effective for primary and
      secondary prevention of thromboembolic events. However, questions persist about
      the risks and management of over-anticoagulation. For reversal of excessive
      anticoagulation by warfarin, AVK withdrawal, oral or parenteral vitamin K
      administration, prothrombin complex or fresh frozen plasma may be used, depending
      on the excess of anticoagulation, the existence and site of active bleeding,
      patient characteristics and the indication for AVK. In over-anticoagulated
      patients, vitamin K aims at rapid lowering of the international normalized ratio
      (INR) into a safe range to reduce the risk of major bleeding and therefore
      improving patient outcome without exposing the patient to the risk of
      thromboembolism due to overcorrection, resistance to AVK, or an allergic reaction
      to the medication. The risk of bleeding increases dramatically when the INR
      exceeds 4.0-6.0, although the absolute risk of bleeding remains fairly low, <5.5
      per 1000 per day. Patient characteristics, including advanced age, treated
      hypertension, history of stroke, and concomitant use of various drugs, affect the
      risk of bleeding. The absolute risk of thromboembolism associated with
      overcorrection appears to be in the same range as the risk of bleeding due to
      over-anticoagulation. The use of vitamin K in patients with warfarin over
      anticoagulation lowers excessively elevated INR faster than withholding warfarin
      alone; however, it has not been clearly demonstrated that vitamin K treatment
      does, in fact, lower the risk of major hemorrhage. As vitamin K administration
      via the intravenous route may be complicated by anaphylactoid reactions, and via
      the subcutaneous route by cutaneous reactions, oral administration is preferred.
      A dose of 1-2.5mg of oral phytomenadione (vitamin K(1)), reduces the range of INR
      from 5.0-9.0 to 2.0-5.0 within 24-48 hours, and for an INR >10.0, a dose of 5mg
      may be more appropriate. Overcorrection of the INR or resistance to warfarin is
      unlikely if the above doses of vitamin K are used. Vitamin K is less effective
      for over-anticoagulation after treatment with acenocoumarol or phenprocoumon than
      after treatment with warfarin.

PMID- 14967066
TI  - Failure of aspirin to prevent atherothrombosis: potential mechanisms and
      implications for clinical practice.
AB  - Aspirin (acetylsalicylic acid) reduces the odds of serious atherothrombotic
      vascular events and death in a broad category of high risk patients by about one
      quarter. The mechanism is believed to be inhibition of thromboxane biosynthesis
      by inactivation of platelet cyclo-oxygenase-1 enzyme. However, aspirin is not
      that effective; it still fails to prevent the majority of serious vascular
      events. Mechanisms that may account for the failure of aspirin to prevent
      vascular events include non-atherothrombotic causes of vascular disease, non
      adherence to aspirin therapy, an inadequate dosage, alternative "upstream"
      pathways of platelet activation (e.g. via stimulation of the ADP, collagen or
      thrombin receptors on platelets), aspirin-insensitive thromboxane biosynthesis
      (e.g. via monocyte cyclo-oxygenase-2), or drugs that interfere with the
      antiplatelet effects of aspirin. Genetic or acquired factors may further modify
      the inhibitory effects of aspirin on platelets (e.g. polymorphisms involving
      platelet-associated proteins, increased platelet turnover states). Identification
      and treatment of the potential causes of aspirin failure could prevent at least
      another 20% of serious vascular events (i.e. over and above those that are
      currently prevented by aspirin). There is currently no role for routine
      laboratory testing to measure the antiplatelet effects of aspirin. Clinicians
      should ensure that patients at high risk of atherothrombosis (>3% risk over 5
      years) are compliant with aspirin therapy and are taking the correct dosage (75
      150 mg/day). Patients who cannot tolerate aspirin, are allergic to aspirin, or
      have experienced recurrent serious atherothrombotic events whilst taking aspirin,
      should be treated with clopidogrel, and patients with acute coronary syndromes
      benefit from the combination of clopidogrel plus aspirin. Future research is
      required to standardize and validate laboratory testing of the antiplatelet
      effects of aspirin and to identify treatments that can both improve these
      laboratory measures and reduce the risk of future atherothrombotic events.

PMID- 14967067
TI  - Novel activating and inactivating mutations in the integrin beta1 subunit A
      domain.
AB  - The ligand-binding activity of integrins is regulated by shape changes that
      convert these receptors from a resting (or inactive) state to an active state.
      However, the precise conformational changes that take place in head region of
      integrins (the site of ligand binding) during activation are not well understood.
      The portion of the integrin beta subunit involved in ligand recognition contains
      a von Willebrand factor type A domain, which comprises a central beta-sheet
      surrounded by seven alpha helices (alpha1-alpha7). Using site-directed
      mutagenesis, we show here that point mutation of hydrophobic residues in the
      alpha1 and alpha7 helices (which would be predicted to increase the mobility of
      these helices) markedly increases the ligand-binding activity of both integrins
      alpha5beta1 and alpha4beta1. In contrast, mutation of a hydrophilic residue near
      the base of the alpha1 helix decreases activity and also suppresses exposure of
      activation epitopes on the underlying hybrid domain. Our results provide new
      evidence that shifts of the alpha1 and alpha7 helices are involved in activation
      of the A domain. Although these changes are grossly similar to those defined in
      the A domains found in some integrin alpha subunits, movement of the alpha1 helix
      appears to play a more prominent role in betaA domain activation.

PMID- 14967068
TI  - Tissue-specific loss of fucosylated glycolipids in mice with targeted deletion of
      alpha(1,2)fucosyltransferase genes.
AB  - Glycolipids in epithelial tissues of the gastrointestinal tract act as receptors
      for enteric bacteria and are implicated in the activation of the intestinal
      immune system. To clarify the genes involved in the fucosylation of the major
      glycolipids, substrate glycolipids and fucosylated products were measured in
      tissues of wild-type and mutant mice lacking alpha(1,2)fucosyltransferase genes
      FUT1 or FUT2. Quantitative determination was performed by TLC-immunostaining for
      GA1 (Gg4Cer), FGA1 (fucosyl GA1), GM1 (II3NeuAc-Gg4Cer), FGM1 (fucosyl GM1), and
      Forssman glycolipids. Both FGM1 and FGA1 completely disappeared from the antrum,
      cecum, and colon of FUT2-null mice, but not those of FUT1-null and wild-type
      mice. Precursor glycolipids, GM1 and GA1, accumulated in tissues of FUT2-null
      mice, indicating that the FUT2-encoded enzyme preferentially participates in the
      fucosylation of GA1 and GM1 in these tissues. Female reproductive organs were
      similarly found to utilize FUT2 for the fucosylation of glycolipids FGA1 (uterus
      and cervix), and FGM1 (ovary), due to their absence in FUT2-null mice. In FUT1
      null mice FGA1 was lost from the pancreas, but was present in wild-type and FUT2
      null mice, indicating that FUT1 is essential for fucosylation of GA1 in the
      pancreas. Ulex europaeus agglutinin-I lectin histochemistry for alpha(1,2)fucose
      residues confirmed the absence of alpha(1,2)fucose residues from the apical
      surface of pancreatic acinar glands of FUT1-null mice. Ileum, epididymis, and
      testis retained specific fucosylated glycolipids, irrespective of targeted
      deletion of either gene, indicating either compensation for or redundancy of the
      alpha(1,2)fucosyltransferase genes in these tissues.

PMID- 14967069
TI  - Ca2+ waves in keratinocytes are transmitted to sensory neurons: the involvement
      of extracellular ATP and P2Y2 receptor activation.
AB  - ATP acts as an intercellular messenger in a variety of cells. In the present
      study, we have characterized the propagation of Ca2+ waves mediated by
      extracellular ATP in cultured NHEKs (normal human epidermal keratinocytes) that
      were co-cultured with mouse DRG (dorsal root ganglion) neurons. Pharmacological
      characterization showed that NHEKs express functional metabotropic P2Y2
      receptors. When a cell was gently stimulated with a glass pipette, an increase in
      [Ca2+]i (intracellular Ca2+ concentration) was observed, followed by the
      induction of propagating Ca2+ waves in neighbouring cells in an extracellular ATP
      dependent manner. Using an ATP-imaging technique, the release and diffusion of
      ATP in NHEKs were confirmed. DRG neurons are known to terminate in the basal
      layer of keratinocytes. In a co-culture of NHEKs and DRG neurons, mechanical
      stimulation-evoked Ca2+ waves in NHEKs caused an increase in [Ca2+]i in the
      adjacent DRG neurons, which was also dependent on extracellular ATP and the
      activation of P2Y2 receptors. Taken together, extracellular ATP is a dominant
      messenger that forms intercellular Ca2+ waves in NHEKs. In addition, Ca2+ waves
      in NHEKs could cause an increase in [Ca2+]i in DRG neurons, suggesting a dynamic
      cross-talk between skin and sensory neurons mediated by extracellular ATP.

PMID- 14967070
TI  - Lung cancer: looking ahead in 2004.

PMID- 14967072
TI  - Management of advanced non-small-cell lung cancer in patients with a performance
      status of 2.
AB  - Patients with a poor performance status (PS) constitute a substantial fraction of
      patients with advanced non-small-cell lung cancer (NSCLC), yet these patients
      have been largely excluded from clinical research in the past decade. Despite the
      proven benefits of chemotherapy in patients with a good PS, cooperative group
      trials in the 1980s showed that patients with a PS of 2 did not benefit from
      chemotherapy and, in fact, had high rates of morbidity and mortality, a notion
      that came to dominate clinical practice for the next 2 decades. More recent
      studies demonstrate that these patients indeed have a worse prognosis than those
      with a better PS. However, chemotherapy seems to provide a benefit, at least in
      terms of symptom improvement, and may improve survival as well. A recent
      comparison of single-agent therapy with combination chemotherapy showed an
      advantage for patients with a PS of 2 treated with the combination regimen,
      without a detriment to quality of life. Dedicated studies in patients with a PS
      of 2 are urgently needed. More effective chemotherapy and better supportive care
      may allow extension of benefits of chemotherapy in advanced NSCLC to patients
      with a PS of 2. Ongoing trials are in progress to further test the role of
      molecular-targeted agents alone or in combination with standard chemotherapeutic
      agents in this subset of patients.

PMID- 14967073
TI  - Prognostic significance of micrometastasis in non-small-cell lung cancer.
AB  - Accurate staging of non-small-cell lung cancer (NSCLC) determines prognosis and
      facilitates decisions regarding treatment options. Unfortunately, even after an
      apparently complete resection in patients with stage I disease, the recurrence
      rates range from 25% to 50%, and overall survival is not encouraging. One
      possible reason for this may be that those patients with a poor outcome actually
      have more extensive disease, with occult locoregional and/or distant metastasis
      than originally identified by routine pathologic staging techniques. There is now
      a sizable body of literature on the detection and possible prognostic role of
      occult disease in lung cancer. The majority of these studies are based on
      immunohistochemical analysis of lymph nodes and/or bone marrow, but a handful of
      studies use molecular approaches. The purpose of this review is to summarize and
      critique the current literature on occult tumor cell spread to lymph nodes and
      bone marrow in patients with NSCLC. Based on this literature, we believe that the
      prognostic significance of bone marrow micrometastasis remains unclear. However,
      the majority of studies indicate that occult lymph node disease is associated
      with a poor outcome. Thus, our ability to detect individual tumor cells could
      result in more accurate staging of NSCLC in patients and would potentially lead
      to the development of novel therapies, as well as influence decisions regarding
      the use of appropriate multimodality treatment strategies, the choice of surgical
      technique, and extent of dissection. As data accumulate, the presence or absence
      of occult nodal involvement should probably be considered at the next revision of
      the staging system for NSCLC.

PMID- 14967074
TI  - Future directions: oncolytic viruses.
AB  - Oncolytic viruses offer a promising new modality for cancer treatment. The
      strategy of this therapy is to develop viruses capable of selectively infecting
      and replicating in malignant tumor cells. Oncolytic viruses can spread and
      destroy malignant tumors without deleterious effects in normal tissues. These
      viruses are genetically engineered based on both the biology of replicating
      viruses and the major genetic defects in human cancer cells, so that they can
      replicate in cancer cells but not in normal cells. The key to the development of
      such viruses is the identification of viral genes, the deletion or modification
      of which enables tumor-specific cell destruction. Several clinical trials have
      demonstrated the safety of oncolytic viruses as cancer therapy and have also
      shown some encouraging results. Much evidence suggests that oncolytic viral
      therapy works in synergy with standard cancer therapies. In this review, we will
      focus on the oncolytic viruses that may be beneficial to patients with lung
      cancer in the near future.

PMID- 14967075
TI  - Trastuzumab plus docetaxel in HER2/neu-positive non-small-cell lung cancer: a
      California Cancer Consortium screening and phase II trial.
AB  - HER2 is reported to be overexpressed in 20% of cases of non-small-cell lung
      cancer (NSCLC), principally adenocarcinoma. Trastuzumab is a monoclonal antibody
      against HER2 that, when combined with a taxane, improves survival compared with
      chemotherapy alone in advanced breast cancer. In view of these observations, we
      conducted a phase II HER2 screening and efficacy trial of trastuzumab plus weekly
      docetaxel in cases of advanced NSCLC in which primary platinum-based therapy had
      failed. Patients with advanced or metastatic NSCLC were screened for HER2
      overexpression by immunohistochemistry. Patients with HER2-positive tumors (2+ or
      3+) were initially randomized to either single-agent trastuzumab or docetaxel.
      After completing 2 treatment cycles, all patients went on to receive the
      trastuzumab/docetaxel combination regardless of response to the single agents.
      Treatment consisted of docetaxel 30 mg/m2 weekly for 6 weeks followed by a 2-week
      break and trastuzumab 4 mg/kg intravenously on week 1 followed by 2 mg/kg per
      week thereafter. Cycle length was 8 weeks. Sixty-nine patients with NSCLC (33
      men, 36 women) were screened between August 1999 and March 2001. Only 13 patients
      (19%) had HER2-positive disease; all 13 enrolled in the efficacy trial. Of 9
      patients receiving docetaxel alone, 1 partial response (PR) was seen. None
      responded to trastuzumab alone. The overall outcomes to the sequence of single
      agent therapy followed by combination therapy included a PR rate in 8% of cases,
      stable disease in 23%, progression in 46%, and nonassessable disease in 23%.
      Estimated event-free and overall survival times were 4.3 and 5.7 months,
      respectively. Treatment was well tolerated. The screening component of this trial
      demonstrated that the target population for trastuzumab therapy in NSCLC is
      relatively small. Because of the limited clinical activity of trastuzumab-based
      therapy in this cohort and the similar disappointing reports from other studies
      of trastuzumab in NSCLC, this trial was closed to further accrual. In view of the
      limited target population for HER2 inhibition, future efforts and resources
      should be directed toward molecular targets other than HER2 in NSCLC.

PMID- 14967076
TI  - Non-small-cell lung cancer in elderly patients: influence of age on vinorelbine
      oral pharmacokinetics.
AB  - The majority of cancer-related deaths are attributed to lung carcinoma. Age
      increases this incidence, which is also likely associated with physiologic
      modifications that affect drug pharmacokinetics and metabolism. Therefore,
      knowledge of pharmacokinetics in elderly patients is one of the major factors in
      deciding whether or not to reduce the dose to prevent toxicity. This phase II
      study was aimed at evaluating the influence of age on oral vinorelbine
      pharmacokinetics in elderly patients with non-small-cell lung cancer (NSCLC).
      Inclusion criteria were > 70 years of age; histologically or cytologically proven
      NSCLC; inoperable stage IIIB, IV, or delayed relapse of any stage becoming
      unresectable; Karnofsky performance status > 80%; and normal hematology and
      biochemistry. Blood-limited sampling at intervals of 1.5, 3, and 24 hours after
      dosing was performed during the first administration of oral vinorelbine at 60
      mg/m2. Bayesian pharmacokinetic parameters were calculated through previously
      published nonlinear mixed-effect modeling (NONMEM), and compared with a reference
      population of 52 patients (age, 56 years 12) selected from vinorelbine
      pharmacokinetic database. There were 48 patients evaluable for pharmacokinetics
      out of the 52 elderly patients enrolled (age, 74 years 3). There was no
      difference between pharmacokinetic parameters, including the bioavailability
      factor evaluated by NONMEM, even without intravenous administration, and a
      similar interindividual variability (32%-33%) was observed between the 2 groups.
      Furthermore, no correlation between age (range, 31-82 years) and oral vinorelbine
      total clearance was observed in 100 patients pooled together. Therefore, no
      requirement for oral vinorelbine dose reduction was suggested from a
      pharmacokinetic standpoint.

PMID- 14967077
TI  - The impact of aging on chemotherapy.

PMID- 14967078
TI  - Cyclooxygenase-2 inhibitors in lung cancer.
AB  - Prostanoids produced by the arachidonic acid pathway play an important role in
      multiple stages of carcinogenesis and progression of cancer. Cyclooxygenase
      (COX), which exists in 2 isoforms, is the rate-limiting enzyme in the COX
      pathway. Cyclooxygenase-1 is constitutively expressed in normal tissues and is
      essential for several important physiologic functions. Cyclooxygenase-2 is
      selectively overexpressed in neoplastic and inflammatory tissues. Non-small-cell
      lung cancer (NSCLC), especially adenocarcinomas, overexpress COX-2, which
      contributes to the progression of malignancy by several mechanisms. This
      represents the basis of therapy with COX-2 inhibitors. Cyclooxygenase-2
      inhibitors, which are currently in clinical use for the management of
      inflammatory arthritis, are well tolerated by patients. They exhibit anticancer
      activity by several mechanisms including induction of apoptosis, inhibition of
      angiogenesis, and decreased invasiveness and metastatic potential. These effects
      have been documented in several preclinical studies. Clinical efficacy of COX-2
      inhibitors in the treatment of NSCLC is presently undergoing evaluation.

PMID- 14967079
TI  - Systematic review of intratympanic gentamicin in Meniere's disease.
AB  - OBJECTIVES: To assess and summarize the best available evidence for the use of
      intratympanic gentamicin in patients with Meniere's disease with respect to
      improvement of vertigo, tinnitus, and change in hearing. METHODS: Comprehensive
      electronic searches were conducted on the databases of MEDLINE, EMBASE, and the
      Cochrane Central Register of Controlled Trials. All generated titles were
      reviewed, and potentially relevant articles were assessed for inclusion. Data
      from included articles were extracted and summarized. RESULTS: Overall pooled
      results on vertigo control revealed complete or substantial control in 89% of
      patients (study range 73-100%). Hearing was worsened in 26% (0-90%). Subjective
      improvement in tinnitus was seen in 57% of patients (0-82%). Different treatment
      protocols all resulted in similar rates of vertigo control. CONCLUSIONS:
      Intratympanic gentamicin appears effective in controlling the symptoms of
      Meniere's disease, regardless of the protocol used. Although the literature on
      this treatment is extensive, there is a likelihood of significant bias in many
      currently published reports. There is a clear need for a prospective, randomized,
      blinded, placebo-controlled trial to assess the true effectiveness of this
      treatment.

PMID- 14967080
TI  - Postoperative parathyroid hormone level as a predictor of post-thyroidectomy
      hypocalcemia.
AB  - OBJECTIVES: To evaluate levels of parathyroid hormone following total
      thyroidectomy in order to ascertain its ability to predict postoperative
      hypocalcemia. To establish standardized criteria permitting the safe discharge of
      total thyroidectomy patients within 13 hours of surgery. METHODS: This is a
      prospective study in which parathyroid hormone levels were tested in 54
      consecutive patients who underwent total thyroidectomy. Levels were measured
      postoperatively at 6, 12, and 20 hours. Corrected calcium levels were also
      measured at 6, 12, and 20 hours in accordance with the preexisting protocol.
      RESULTS: Statistical analysis demonstrates that patients with corrected calcium
      levels greater than or equal to 2.14 mmol/L and parathyroid hormone levels
      greater than or equal to 28 ng/L at 12 hours post-thyroidectomy can be discharged
      without further need for calcium monitoring. The analysis also demonstrates that
      patients with 12-hour parathyroid hormone levels less than or equal to 20 ng/L
      are at significant risk of developing hypocalcemia. CONCLUSION: Parathyroid
      hormone levels in conjunction with corrected calcium values are accurate
      predictors of the calcium trends of post-thyroidectomy patients. Implementation
      of this protocol can result in shorter hospital stays for the majority of post
      thyroidectomy patients, which can translate into substantial cost savings for the
      health care system.

PMID- 14967081
TI  - Informed consent in otologic surgery: prospective study of risk recall by
      patients and impact of written summaries of risk.
AB  - OBJECTIVES: To evaluate how much patients remember of the risks discussed with
      them about their otologic surgery and to evaluate whether a simple intervention,
      the addition of an information handout, improves recall. STUDY DESIGN: A
      prospective, randomized trial was undertaken in the setting of an academic
      tertiary care centre. METHODS: Fifty patients undergoing a variety of otologic
      procedures, including mastoidectomy, tympanoplasty, ossiculoplasty, and
      stapedectomy, were verbally consented by the operating surgeon with a standard
      checklist of potential surgical complications and side effects. Two surgeons
      participated in the study (40 patients and 10 patients). Patients were stratified
      into two groups: a higher education group and a lower education group. Within
      each group, patients were randomized to either a control group, consisting of a
      verbal explanation only, or an intervention group, which added a written handout
      to the verbal explanation. A follow-up telephone interview was conducted at an
      average of 20.6 days (range 14-53) to survey for recall of the complications
      discussed. MAIN OUTCOME MEASURES: The main outcome measure is risk recall. This
      is analyzed by education level and written sheet intervention. Other parameters
      examined are patient demographics, time elapsed from when the consent was
      obtained, and surgeon obtaining the consent. RESULTS: All 50 patients were
      interviewed in follow-up. Twenty-two patients received the handout (intervention
      arm), and 28 patients served as the control group. Overall recall, expressed as a
      percentage of risks explained, was 54% for the entire study group. For those who
      received the handout, the recall rate was 51%, whereas the rate was actually
      higher, at 56%, for those who did not receive the handout. This difference was
      not statistically significant. Of the specific risks discussed, patient recall
      was consistently high for the complications of facial nerve paralysis, 88%, and
      for complete hearing loss, at 88%. Other risks, such as dizziness, 31%, and
      change in taste, 36%, were not as commonly recalled. Receiving the handout made
      only a significant difference with one complication, facial nerve paralysis.
      CONCLUSION: The addition of a handout did not significantly alter recall of
      potential complications of otologic surgery with the exception of facial nerve
      paralysis.

PMID- 14967082
TI  - Cricoarytenoiditis in rheumatoid arthritis: radiologic and clinical study.
AB  - The cricoarytenoid (CA) joint involvement in rheumatoid arthritis (RA) is not
      uncommon. In this study, clinical assessment, laryngeal endoscopy, and high
      resolution computed tomography (HRCT) were used in 15 patients with RA to
      evaluate the diagnostic criteria of CA joint involvement. Symptoms owing to CA
      joint involvement were present in 66.6% of the patients. The frequency of
      involvement was 13.3% on laryngeal endoscopy but 80.0% with HRCT assessment. The
      most common HRCT findings were CA prominence (46.6%), density and volume changes
      (46.6%), and CA subluxation (39.9%). In some of the patients, soft tissue
      swelling (20%) near the CA joint and narrowing in the piriform sinus (33.3%) were
      also observed. Radiologic abnormalities related to CA joint involvement generally
      precede clinical symptomatology. Therefore, HRCT evaluation may be a useful
      method in the assessment of CA joint involvement in RA patients to exclude
      possible causes of laryngeal signs and symptoms.

PMID- 14967083
TI  - Cilia ultrastructure in children with Down syndrome.
AB  - Chronic sinusitis, otitis media with effusion, and upper respiratory tract
      infections are commonly found in patients with Down syndrome. These diseases are
      generally felt to be secondary to depressed immune function and altered
      craniofacial dimensions. Recently, a cilia ultrastructure abnormality was found
      in a child with Down syndrome. This study is the first to be carried out to
      determine if cilia ultrastructure abnormalities are prevalent in the population
      with Down syndrome. Four of 10 patients had documented cilia abnormalities, but
      these were present in the background of normal cilia, suggesting that they were
      the result rather than the cause of chronic sinusitis. Similarly, nasal
      epithelium metaplasia was detected in 50% of the patients. Chronic sinusitis,
      otitis media with effusion, and recurrent upper respiratory tract infections in
      children with Down syndrome cannot generally be attributed to primary cilia
      ultrastructure abnormalities.

PMID- 14967084
TI  - Retrospective analysis of our cases with sudden hearing loss.
AB  - OBJECTIVE: To determine the prognostic factors and healing ranges of patients
      treated for sudden hearing loss (SHL). PATIENTS AND METHODS: In our study, 33
      patients treated for SHL were evaluated between March 1995 and October 2001
      retrospectively. After the routine examinations, first audiograms were done. The
      audiograms were classified as hearing loss in low frequencies, high frequencies,
      and flat using the Shey and Rubin classification systems. All patients were
      treated with the same standard regimen. The benefits of treatment were evaluated
      with the Siegel classification. RESULTS: Various amounts of hearing gains were
      obtained in 17 of 21 patients treated in the first 5 days. No gain was obtained
      in 5 of 12 patients, who re-presented after the first 5 days of SHL. There was a
      statistically significant difference between the two groups (p =.005). There was
      hearing gain in all nine patients who had upward-sloping type of audiograms.
      Hearing gain was obtained in 8 of 12 downward-sloping type and 7 of 12 flat-type
      audiograms. There was a significant difference between the raising type group and
      the other groups (p =.04 and p =.014). Also, in 6 of 14 patients with vertigo and
      in 4 of 12 with bilateral sensorineural hearing loss (SNHL), there was no gain.
      CONCLUSION: The prognosis of SHL is found to be better in patients who present
      early and mild SNHL and unilateral cases and worse in vertigo, bilaterally severe
      SNHL, and childhood.

PMID- 14967085
TI  - Role of microbial toxins in the induction of glucocorticoid receptor beta
      expression in an explant model of rhinosinusitis.
AB  - BACKGROUND: Glucocorticoids (GCs) are the most potent agents currently available
      for relieving the symptoms of chronic rhinosinusitis. The pathogenesis and
      molecular basis of GC insensitivity in allergic rhinosinusitis are unknown.
      Studies done on patients with GC-insensitive asthma demonstrated an
      overexpression of GC receptor beta (GRbeta), an abnormal splice variant and an
      endogenous inhibitor of the classic GC receptor alpha. The mechanisms that induce
      the overexpression of GRbeta remain poorly understood. OBJECTIVE: To study the
      role of Staphylococcus-derived enterotoxin in inducing GRbeta in a human explant
      model of rhinosinusitis. METHODS: Nasal tissue was obtained from inferior
      turbinates of nonatopic and ragweed-sensitive patients. Tissue samples from
      nonatopic patients were incubated in the presence and absence of superantigen
      (SAg) of staphylococcal enterotoxin. In addition, tissue samples from ragweed
      sensitive patients were incubated with and without ragweed allergen in the
      presence or absence of SAg. The expression of GRbeta was assessed by
      immunocytochemistry using a specific polyclonal antibody to GRbeta. RESULTS: SAg
      increased the expression of GRbeta in both atopic and nonatopic tissue. The
      highest increase in the expression of GRbeta occurred when atopic nasal tissue
      was incubated with both ragweed and SAg. CONCLUSION: SAg-induced GRbeta is an
      important modulator of steroid sensitivity in chronic rhinosinusitis.

PMID- 14967086
TI  - Cost comparison of auditory brainstem response versus magnetic resonance imaging
      screening of acoustic neuroma.
AB  - The cost-effectiveness of current diagnostic approaches employed in patients with
      suspected acoustic neuroma was evaluated. Currently, patients with signs and
      symptoms suggestive of acoustic neuroma, such as sudden unilateral hearing loss
      and/or tinnitus, undergo auditory brainstem response (ABR) screening tests to
      rule out this condition. If the ABR is normal, acoustic neuroma can be ruled out.
      However, if the ABR is abnormal, magnetic resonance imaging (MRI) or computed
      tomography is necessary to confirm the diagnosis. When one considers the total
      costs of this screening approach, one can ask whether straight MRI screening of
      all of these patients would be a more cost-effective approach to diagnosing this
      condition. A retrospective chart review of patient records obtained from the
      acoustic diagnostics laboratory at Hotel Dieu Hospital, Kingston, Ontario, was
      performed. A database of patients who have undergone ABR testing over the past 2
      years was compiled and analyzed to assess how many of them went on to receive
      MRI. The total costs (based on Ontario Health Insurance Plan [OHIP] fee schedule
      rates) of this approach were compared with the estimated costs of straight MRI
      screening performed on the same patient population. By making such an analysis,
      decisions regarding the most cost-effective approach to screening for acoustic
      neuroma can be objectively assessed.

PMID- 14967087
TI  - Delayed facial palsy after vestibular schwannoma resection: clinical data and
      prognosis.
AB  - PURPOSE: The object of the present study was to review a series of surgically
      removed vestibular schwannoma tumours to establish the incidence of delayed
      facial palsy and to evaluate the course of recovery according to the possible
      etiology (surgical postoperative edema or viral reactivation) with reference to
      the time of onset. MATERIALS AND METHODS: The study group was composed of 98
      patients with vestibular schwannoma. Sex, age, location, and extent of tumour and
      postoperative complications were all taken into consideration in the final
      evaluation. The course of each patient's postoperative facial function was graded
      according to House and Brackmann's six-grade scale. The incidence and the time of
      onset of the delayed facial palsy were also evaluated. RESULTS: The deterioration
      in the facial function was found to be delayed in 25 of the 98 patients (26%); of
      these, it occurred in the first 5 days after surgery in 11 cases, between 6 and
      13 days in 10 cases, and after 15 days in 14 patients. The incidence rate of the
      delayed facial dysfunction was not influenced by age, sex, or the size of the
      tumour. The prognosis of the facial dysfunction was favourable in the majority of
      cases, and, in fact, there were only five grade III to IV cases 1 year later.
      Facial dysfunction was over grade III in the majority of the latter five cases,
      and the period of recovery was long. CONCLUSIONS: Eighty percent of our patients
      with delayed facial palsy following vestibular schwannoma resection were
      classified as having excellent or good function. In the remaining patients who
      had a less favourable recovery, the palsy was more severe, and the onset occurred
      after some time. This seems to agree with those who are of the opinion that the
      complication is due to viral reactivation. In these patients, it is advisable to
      start aggressive medical therapy with antiviral agents such as acyclovir as soon
      as possible.

PMID- 14967088
TI  - Blastomycosis presenting as a locally invasive intranasal mass: case report and
      literature review.

PMID- 14967089
TI  - Peritonsillar abscess in a tonsillectomized patient.

PMID- 14967090
TI  - Tympanostomy preceding tympanoplasty: could it be a new approach for the
      management of adhesive otitis media.

PMID- 14967091
TI  - [Prevalence of anemia and its correlation with clinical parameters in patients
      from a multidisciplinary heart failure unit].
AB  - BACKGROUND AND OBJECTIVE: There is a high prevalence of anemia in patients with
      heart failure which is related to their outcome. The aim of the study was to
      evaluate the prevalence of anemia (haemoglobin < 12 g/dl) in patients attended in
      a Multidisciplinary Heart Failure Unit and to analyze the correlation of
      hemoglobin levels and the presence of anemia with demographic, clinic, biological
      and therapeutic parameters. PATIENTS AND METHOD: Between August 2001 and February
      2003, 330 patients were attended (mean age [SD], 68.0 [9.3] years). Simple lineal
      regression, multiple lineal regression, *2 test, Student t test and Kruskal
      Wallis test were used for statistical analysis. RESULTS: 30% patients had anemia.
      We found a significant correlation between plasmatic hemoglobin levels and age,
      gender, etiology of heart failure, coexistence of diabetes, absence of smoking
      habit, functional class, quality of life, plasmatic levels of urea, creatinine
      and cholesterol, treatment with diuretics and nitrates and the absence of
      treatment with betablockers. Surprisingly, there was no relationship between
      treatment with angiotensin-converting enzyme inhibitors, antiplatelet drugs or
      anticoagulants and the presence of low levels of hemoglobin. CONCLUSIONS: The
      prevalence of anemia in a general population with heart failure is high.
      Plasmatic hemoglobin levels were related to several parameters, mainly age,
      gender, functional class and plasmatic levels of urea and cholesterol.

PMID- 14967092
TI  - [Paraoxonase 1 gene 192 polymorphism, physical activity and lipoprotein in
      women].
AB  - BACKGROUND AND OBJECTIVE: Regular physical activity is associated with an
      increase in high-density lipoprotein cholesterol (HDL-C), whose antioxidant and
      protective effect for coronary artery disease is well known. Paraoxonase-1 (PON1)
      is an enzyme related with the antioxidant activity of HDL. The PON1 gene has
      several genetic polymorphisms; one of them locates in codon 192, whose alleles Q
      and R are associated with low and high PON1-activity, respectively. The objective
      of this study was to determine whether physical activity has different effects on
      the lipid profile in women depending on the PON1-192 genotype. PATIENTS AND
      METHOD: Six hundred and fifty-one women from a cross-sectional risk-factor study
      were included in this retrospective cohort study. We analyzed anthropometrical
      characteristics, serum lipids and lipoproteins, blood pressure, PON1-192
      genotypes and menopause. We used the Minnesota Leisure Time Physical Activity
      Questionnaire to assess the daily physical activity in the previous year.
      RESULTS: Women included in the study were classified into three categories by
      tertiles of daily physical activity. Although no differences in the lipidic
      parameters were found, we observed an increasing trend in HDL-C concentration and
      a decreasing trend in log-triglyceride-to-HDL-cholesterol ratio with increasing
      physical activity in RR homozygous women. In subgroup analyses, we observed that
      the association of high physical activity and increased HDL-C concentration or
      decreased log-triglyceride-to-HDL-cholesterol ratio were exclusive for RR
      homozygous non-menopausal women. CONCLUSIONS: The results of this study suggest
      that PON1-192 polymorphism could modulate the effect of physical activity on HDL
      C concentration and on triglyceride-rich lipoprotein catabolism in non-menopausal
      women.

PMID- 14967093
TI  - [In-patient treatment decisions].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to identify the extent to
      which treatment decisions for medical in-patients in three hospitals in Catalunya
      are supported by published evidence. PATIENTS AND METHOD: In a retrospective,
      cross-sectional study, main diagnosis-treatment pairs (DTPs) were identified for
      980 hospital discharges. The Cochrane library and MEDLINE from 1966 to 1998 were
      searched for systematic reviews or, in their absence, randomized controlled
      clinical trials (RCT) that supported the treatment given for each diagnosis. The
      level of evidence found for each DTP was classified. Descriptive analyses for
      patients and different DTP were performed. RESULTS: A systematic review or RCT
      (level I) was found for 65.4% of the 980 patients. In 32.6% of cases, there was
      only non-experimental or consensus evidence (level II) and in 2% there was no
      good evidence for the treatment given (level III). An analysis of the 598 unique
      pairs reduced the percentage of cases supported by level I evidence (55.7) with a
      proportionate increase in level II (41%). There were some differences in the
      proportion of cases in each evidence level by diagnostic group. CONCLUSIONS: For
      about two thirds of patients and a half therapeutic decisions in these three
      centres, there was a published RCT or a systematic review, with variations
      according to diagnostic groups. More robust and objective instruments are needed
      to assess the degree to which scientific evidence is applied in clinical
      practice.

PMID- 14967094
TI  - [Anti-neutrophil cytoplasmic antibodies in the diagnosis of ulcerative colitis
      and Crohn's disease].
AB  - BACKGROUND AND OBJECTIVE: We assessed the prevalence and diagnostic value of
      antineutrophil cytoplasmic antibodies (ANCA) with a perinuclear pattern (pANCA)
      in patients with Crohn's disease (CD) and ulcerative colitis (UC). PATIENTS AND
      METHOD: pANCA were determined by indirect immunofluorescence and positive results
      were confirmed by ELISA. RESULTS: We included 117 patients with CD, 72 with UC
      and 2 with indeterminate colitis. One CD patient (0.9%) and 6 with UC (8.3%) had
      a positive pANCA result. Sensitivity, specificity, positive and negative
      predictive value, and positive and negative likehood ratio of pANCA for a
      diagnosis of UC (vs CD) were 8%, 99%, 86%, 64%, 8 and 0.9, respectively, thus
      indicating the need to standardize the methodology. No differences were observed
      with regard to age, tobacco consumption, localization and extension of UC and
      need of immunosuppressive agents according to pANCA. CONCLUSIONS: In our setting,
      the prevalence of pANCA is very low (8%) in UC and exceptional (< 1%) in CD. As a
      result, pANCA sensitivity for a diagnosis of UC in patients with inflammatory
      bowel disease is also very low, yet the specificity is very high.

PMID- 14967095
TI  - [What is the relevance of anemia treatment among the novel therapies of heart
      failure?].

PMID- 14967096
TI  - [Serologic disease markers in inflammatory bowel disease].

PMID- 14967097
TI  - [Medical education to insert physicians into the labour market (1994-2002)].

PMID- 14967098
TI  - [Platelet transfusion; concentrates from single or from multiple donors?].

PMID- 14967099
TI  - [Cloning and stem cells].
AB  - Applied cloning technologies have become a great scientific advance. Many of
      their biotechnological applications (stem cells, transplants, tissue therapy) are
      improving medical fields to extents that we could not imagine a few years ago.
      Thus, for example, we are now able to produce cellular and tisular spares via
      differentiating stem cells in vitro. Yet the scientific community maintains a
      vibrant debate over technical aspects and applications of cloning technologies,
      with most scientists positioned against reproductive cloning while agreeing on
      its therapeutic use. This article summarizes the foremost applications and
      problems related to cloning and stem cells technologies, from an academic and
      health professionals' point of view.

PMID- 14967100
TI  - [Nonsteroidal anti-inflammatory drugs use and Helicobacter pylori eradication].

PMID- 14967101
TI  - [Mutation of the prothrombin gene (G20210A) in a patient with cerebral venous
      sinus thrombosis and bilateral deep vein thrombosis].

PMID- 14967102
TI  - [Celiac disease and IgA nephropathy: a double face coin?].

PMID- 14967103
TI  - [Isolation of Leclercia adecarboxylata from wound exudate of a diabetic patient].

PMID- 14967104
TI  - [Is systematic use of drug-eluting stents justified? Arguments in favour].
AB  - The efficacy of drug-eluting stents measured as the late loss, percentage
      neointimal volume, restenosis, target lesion revascularization and major cardiac
      events is significantly better than that of bare metal stents. The incidence of
      thrombosis and aneurysms is similar. Although there is a slight increase in late
      apposition, this is not followed by an increase in cardiac events. Despite the
      arguments against the routine use of drug-eluting stents, their cost is the only
      limiting factor for their widespread use.

PMID- 14967105
TI  - [Is systematic use of drug-eluting stents justified? Arguments against].
AB  - Antiproliferative drug-eluting stents represent a miles tone in advances in
      interventional cardiology. The amount and quality of the scientific evidence now
      show these new stents to be highly effective in reducing neointimal
      proliferation, and hence the process of restenosis. Their clinical impact can be
      expected to become relevant in terms of both increased indications for
      angioplasty and the extent of stent usage. However, at this time the systematic
      use of drug-eluting stents for all patients is not considered justified, because
      of their limited availability, gaps in our knowledge of their safety, and because
      their unquestioned clinical benefits have been magnified by exaggerated reports
      of the clinical problem restenosis represents. Currently, the cost of these
      stents remains high, and the cost/benefit ratio for certain patients is
      unfavorable. For these reasons selective use of these new stents is considered
      more reasonable: they should be used only for those patients who will obtain, in
      absolute terms, the greatest clinical benefit.

PMID- 14967106
TI  - [Sirolimus-eluting stents to treat lesions with a high risk of restenosis. Six
      month clinical follow-up in the first 100 patients].
AB  - INTRODUCTION: Sirolimus-eluting stents have been shown to be effective in de-novo
      coronary lesions, reducing restenosis strikingly in a subset of lesions with a
      low or moderate risk of restenosis. We decided to assess their usefulness in
      lesions with a high risk of restenosis. PATIENTS AND METHOD: We included
      consecutive patients with lesions that met at least one of the following
      criteria: a) in-stent restenosis; b) diffuse lesion (>20 mm); c) small vessel (<
      or =2.5 mm), and d) total occlusion. RESULTS: Between June 2002 to December 2002,
      100 patients were included (61 [11] years, 84% men, 21% with diabetes). In all,
      154 lesions were treated (34% diffuse lesions, 36% in small vessels, 20% in-stent
      restenosis and 20% occlusions). An average of 1.6 (0.7) stents were implanted per
      patient. Mean diameter was 2.74 (0.26) mm, mean length was 21 (8.5) mm and total
      stent length per patient was 33 (16) mm. The acute success rate was 98%. After
      the procedure 2 (2%) non-Q-wave infarctions were diagnosed. No episodes of acute
      or subacute thrombosis occurred. During a follow-up period of 8.5 (2) months
      (range 6-12 months) there were two (2%) late thromboses, one of which caused an
      infarction. Target lesion revascularization was required in 3 patients (3%), two
      of whom were the patients with late thrombosis. CONCLUSIONS: Sirolimus-eluting
      stents can be used in lesions with a high risk of restenosis. The rate of
      thrombosis was low, and the use of these stents was associated with a strikingly
      low rate of target lesion revascularization during follow-up.

PMID- 14967107
TI  - [Use of sirolimus-eluting stents in complex lesions: clinical and angiographic
      follow-up].
AB  - INTRODUCTION AND OBJECTIVES: The RAVEL and SIRIUS studies have demonstrated
      important reductions in clinical and angiographic restenosis in lesions treated
      with sirolimus-eluting stents. However, inclusion criteria in both studies
      excluded complex lesions. We studied immediate and long-term results with this
      stent in these complex lesions. PATIENTS AND METHOD: Prospective, observational
      study with clinical and angiographic follow-up of patients who met the exclusion
      criteria used in the RAVEL and SIRIUS studies. All patients were treated in our
      catheterization laboratory between June 2002 and April 2003 with the Cypher
      stent, and 57 patients (68 lesions) were studied in all. The most frequent lesion
      characteristics were excessive length 26.5%; ostial lesions 25%, bifurcations
      23.5%, and severe calcifications 22.1%. Almost half (47%) of the patients had
      diabetes and 68% had multivessel disease. RESULTS: PTCA was successful in all
      patients. There was one major adverse cardiovascular event (MACE) before
      discharge (1 acute Q-wave myocardial infarction). Two episodes of subacute
      thrombosis occurred during the first week. During long-term clinical follow-up
      (8.7 [3.1] months) of all patients, there were 4 MACE (7%): 1 cardiac death, 1
      acute myocardial infarction and 2 revascularizations of the target vessel.
      Intersegmental restenosis was observed by angiography in 4 lesions (8%).
      CONCLUSIONS: Implantation of the Cypher stent in complex lesions is safe and is
      associated, after 6 months of follow-up, with a low incidence of clinical events
      and a very low percentage of angiographic restenosis.

PMID- 14967108
TI  - [Circadian profiles of heart rate and its instantaneous variability in patients
      with chronic Chagas' disease].
AB  - INTRODUCTION AND OBJECTIVES: Impairment of the autonomous nervous system in early
      stages of Chagas' disease is still a matter of debate, although multiple
      approaches (including heart rate response to orthostatism and the Valsalva
      maneuver, and spontaneous variability) have been used to ascertain its
      occurrence. The circadian profile of heart rate and its variability have not been
      investigated in patients with Chagas' disease. PATIENTS AND METHOD: We analyzed
      the 24-hour heart rate by Holter recordings in 63 patients with and without ECG
      alterations, who had positive serological findings for Chagas' disease. These
      results were compared with those in 22 healthy subjects matched for sex and age.
      Mean 24-hour heart rate and its circadian amplitude were analyzed with Cusum
      analysis and nocturnal dip. In a subgroup of 45 subjects (30 with Chagas' disease
      and 15 healthy controls), heart rate instantaneous variability (24-hour pNN50 and
      r-MSSD) and circadian amplitude were also calculated by Cusum analysis. RESULTS:
      24-hour and diurnal heart rates were lower in patients with Chagas' disease than
      in healthy subjects (P<.05). Circadian amplitude and dip were lower in patients,
      but these differences did not reach statistical significance. In the subgroup of
      45 subjects, the reductions in instantaneous heart rate variability (pNN50 and r
      MSSD) in Chagasic patients were small, and circadian amplitudes were preserved,
      when compared with healthy subjects. CONCLUSIONS: The lower heart rate in
      patients with Chagas' disease occurred only during diurnal activity, and
      instantaneous heart rate variability was preserved. These findings suggest an
      alteration in the sympathetic branch of the autonomous nervous system. The
      circadian heart rate profile, which has not been studied previously in patients
      with Chagas' disease, does not seem appreciably blunted in this stage of the
      disease.

PMID- 14967109
TI  - [Effect of the left ventricular pacing site on echocardiographic parameters of
      ventricular dyssynchrony in patients receiving cardiac resynchronization
      therapy].
AB  - INTRODUCTION AND OBJECTIVES: Cardiac resynchronization therapy has been shown to
      be an option in the treatment of patients with congestive heart failure. The
      current indication for this treatment is based on clinical and
      electrocardiographic criteria, although echocardiography has also been shown to
      be a useful tool for the diagnosis of ventricular dyssynchrony. The aim of this
      study was to assess left ventricular dyssynchrony by echocardiography and to
      evaluate the effect of the stimulation site on the magnitude of
      resynchronization. PATIENTS AND METHOD: We studied 25 patients with biventricular
      stimulation (left ventricular lead located in a lateral position in 13 patients,
      and in an anterior position in 12). A complete echo-Doppler evaluation, including
      left ventricular ejection fraction, ventricular diameters and parameters of inter
      and intraventricular dyssynchrony, was performed before implantation and 3
      months after the procedure, with the device connected and disconnected. RESULTS:
      Left ventricular ejection fraction increased significantly from 23.7 (6.5) to
      27.8 (5.5) (P=.007) at 3 months. In the group as a whole, biventricular pacing
      was associated with a significant decrease in all intraventricular dyssynchrony
      parameters (septal-to-lateral wall motion delay and septal-to-posterior wall
      motion delay). This decrease in septal-to-posterior wall motion delay and septal
      to-lateral wall motion delay was significantly greater in patients with the
      electrode implanted in the lateral position (58.1 ms vs 118 ms; P=.02) than with
      the lead in the anterior position (39.5 ms vs 86.5 ms; P=.04). Three patients,
      all with the electrode in an anterior location, were considered non-responders.
      CONCLUSIONS: Left lateral free wall stimulation provided significantly better
      intraventricular resynchronization compared to stimulation at an anterior site.
      Echocardiography is a useful tool to evaluate changes in intra- and
      interventricular synchrony related to the pacing site.

PMID- 14967110
TI  - [Intervention program to improve secondary prevention of myocardial infarction.
      Results of the PRESENTE (early secondary prevention) study].
AB  - INTRODUCTION AND OBJECTIVES: Secondary prevention measures for myocardial
      infarction are inadequate. In Spain, the earlier PREVESE studies provided
      preliminary data. The aim of this study was to document the results of a simple
      intervention program for secondary prevention, implemented during the hospital
      stay. PATIENTS AND METHODS: We included 4174 patients (mean age 63.7 years, 73%
      men) discharged from 110 hospitals after myocardial infarction. Lipid profile was
      determined during the first 24 h after admission, and before discharge patients
      and relatives were informed about the disease and its prevention, and were given
      printed informative materials. The patients were seen again 6 months later.
      RESULTS: After 6 months, 82.9% of the patients were examined and 10% were lost to
      follow-up. Mean blood pressure, weight and body mass index of the sample were
      lower, and lifestyle variables had improved. At discharge 87% were prescribed
      statins, 59.4% beta blockers, 51.2% ACE inhibitors and angiotensin blockers, and
      94.1% antiplatelet drugs. These prescriptions were still being used 6 months
      later. There were substantial improvements in lipid values. CONCLUSIONS: The
      implementation of a simple intervention program for patients with myocardial
      infarction and their relatives, and the determination of lipid levels within 24
      hours of admission, improved the secondary prevention measures at discharge and
      during the 6-month follow-up period. Acceptance of the program among the patients
      was good.

PMID- 14967111
TI  - [Use of the Minnesota Living With Heart Failure Quality of Life Questionnaire in
      Spain].
AB  - INTRODUCTION AND OBJECTIVES: Quality of life is an important end-point in heart
      failure studies, as well as mortality and hospitalization rates. The Minnesota
      Living With Heart Failure Questionnaire is the instrument used most widely to
      evaluate quality of life in research studies. We used this questionnaire to
      evaluate quality of life in a general population attended by a heart failure unit
      in Spain. PATIENTS AND METHOD: 326 patients seen for the first time at the unit
      were evaluated. We analyzed the relationship between the questionnaire score and
      different clinical and demographic factors. RESULTS: The median global score on
      the Minnesota Living With Heart Failure Questionnaire was relatively low (28). We
      found a strong correlation (P<.001) between the score and functional class, sex
      (women had higher scores), and diabetes. We also found a correlation between the
      score and number of hospital admissions in the previous year (P<.001), anemia
      (P<.001) and etiology (P=.01), and a weak trend toward higher scores with
      increasing age (P=.04). The highest scores were observed in patients with valve
      disease disorders (43), and the lowest were seen in patients with alcoholic
      cardiomyopathy (20) and ischemic heart disease (24). We found no correlation with
      time of evolution of heart failure or with left ventricular ejection fraction.
      CONCLUSIONS: The scores on the Minnesota Living With Heart Failure Questionnaire
      in a general population attended by a heart failure unit in Spain were relatively
      low. However, we found a strong correlation between this score and functional
      class, and also between this score and number of admissions in the previous year.
      These results suggest that the questionnaire adequately reflects the severity of
      the disease.

PMID- 14967112
TI  - [Advances in the diagnosis and therapeutic evaluation of heart failure. From
      tonic-unloading treatment to cell transplantation and myocardial regeneration].

PMID- 14967113
TI  - [Epidemiology of heart failure].
AB  - Of all persons aged over 40 years, approximately 1% have heart failure. The
      prevalence of heart failure doubles with each decade of life, and is around 10%
      in persons over 70 years of age. In Spain, heart failure causes nearly 80,000
      hospital admissions every year. As in other developed countries, heart failure is
      the most frequent cause of hospitalization among persons 65 years of age and
      over, and is responsible for 5% of all hospitalizations. The incidence of heart
      failure increases with age, and reaches 1% per year in those over 65. Heart
      failure is a progressive, lethal disorder, even with adequate treatment. Five
      year survival is around 50%, which is no better than that for many cancers. In
      Spain, heart failure is the third leading cause of cardiovascular mortality,
      after coronary disease and stroke. In 2000, heart failure caused 4% of all deaths
      and 10% of cardiovascular deaths in men; the corresponding figures for women were
      8% and 18%. In recent decades the prevalence and number of hospitalizations due
      to heart failure have increased steadily in developed countries. Heart failure
      will probably continue to increase in coming years: although its incidence has
      not materially decreased, survival is increasing due to better treatment. The
      control of risk factors for hypertension and ischemic heart disease, the main
      causes of heart failure in Spain, is the only method to halt the foreseeable
      increase in heart failure in the near future.

PMID- 14967114
TI  - [Stent pseudo-restenosis. Diagnosis using intracoronary ultrasound].

PMID- 14967115
TI  - [Effects of tilt test and beta-adrenergic stimulation on the QT interval in
      normal children and pediatric patients with unexplained syncope].
AB  - In normal children, any procedure that increases heart rate, such as the tilt
      test, may shorten the QT interval. The effect of the tilt test on QT interval in
      children with syncope remains unknown. We analyzed the response of RR and QT
      intervals during a tilt test in 3 groups of children: 28 healthy children (group
      1), 26 with syncope of unknown etiology and negative tilt test results (group 2),
      and 17 with vasovagal syncope (group 3). During the tilt test, RR and QT
      intervals were significantly shortened in groups 1 and 2. In group 3, RR interval
      was lengthened during syncope whereas the QT interval remained constant. QT
      interval lengthening during the tilt test is not a characteristic finding in
      normal children or in children with vasovagal syncope.

PMID- 14967116
TI  - [ST segment elevation during dipyridamole stress testing in a patient without
      coronary lesions].
AB  - We describe a patient who presented transient ST-segment elevation and typical
      chest pain during an ischemia test with dipyridamole and technetium-tetrofosmin.
      Chest pain and electrical alterations disappeared promptly with sublingual
      nitroglycerin. Coronary angiography showed no epicardial lesions, and coronary
      vasospasm was suspected. We discuss possible explanations for this complication.

PMID- 14967117
TI  - [Rupture and intracoronary entrapment of an angioplasty guidewire with the X
      Sizer thromboatherectomy catheter during rescue angioplasty].
AB  - The X-Sizer thromboatherectomy catheter represents an important advance for
      thrombectomy in thrombus-containing lesions, especially in patients who require
      primary and rescue angioplasty. Although it is safe, some complications have been
      reported as its use becomes more widespread. To our knowledge, the intracoronary
      breakage and retention of the angioplasty guidewire has not been reported. We
      describe a case of this rare complication and analyze the causes, prevention and
      treatment alternatives.

PMID- 14967118
TI  - [The entrance of the emergency department].

PMID- 14967120
TI  - [Rural health in a changing world].

PMID- 14967121
TI  - [Profile and burden of care in caregivers of patients with dementia included in
      the ALOIS program].
AB  - AIM: To study the profile and burden of care in carers of patients with dementia
      who participated in the ALOIS program. A second objective was to evaluate
      caregiver satisfaction with the intervention, and changes in caregiver burden
      after participation in the program. DESIGN: Descriptive study of a specific
      intervention with no control group. SETTING: Primary care centers. PARTICIPANTS:
      Principal caregivers of patients with dementia. INTERVENTIONS: Group education
      sessions led by multidisciplinary teams comprising physicians, nurses and social
      workers. MEASURES: Caregiver profile; mean caregiver burden before and 3 months
      after the intervention (Caregiver Burden Interview, Zarit); caregivers'
      evaluation of the program. RESULTS: Participants N=245. Profile (N=173): women
      (83%), mean age 54.6 years (range, 26-83 years), married (82.5%), no formal
      education or primary school only (70.2%), housewife (54.3%), patient's daughter
      (58.5%). More than 60% of the caregivers received informal help, and fewer than
      5% received formal help. 72.5% of the caregivers were considered overburdened at
      the start of the intervention, and the burden was greater in older caregivers. No
      differences were detected in caregiver relation to the patient, marital status or
      employment status of the caregiver. Participants rated the program very highly,
      emphasizing the opportunity to share their experiences with other caregivers and
      to obtain knowledge and skills that helped them provide better care. Pre- and
      postintervention burden of care was compared in 68 participants (54.76+/-15.16
      points vs 53.02+/-12.55), and no statistically significant difference was found.
      CONCLUSIONS: The burden of care was high among caregivers, and increased as
      caregivers aged. Caregivers considered participation in the program to be highly
      useful. Care for caregivers should form part of care provided for patients with
      dementia.

PMID- 14967122
TI  - [Commentary: how effective are support interventions for caregivers of patients
      with dementia?].

PMID- 14967123
TI  - [Clinical management of consultations: clinical content and predictability (SyN
      PC Study)].
AB  - OBJECTIVES: To describe care activity as a function of the nature of the
      consultation (predictability) and the needs of the patients (clinical content).
      To analyse the relationship of these with the characteristics of the
      consultation, of the patient and of the centre. DESIGN: Multi-centre,
      descriptive, observational study. SETTING: Primary care. Area 17 of the Health
      Department of the Community of Valencia, with 197316 inhabitants and 12 health
      centres. PARTICIPANTS: Information gathering in real time by outside observer.
      Stratified randomised sampling of 2051 patients who gave rise to 3008 reasons for
      medical consultation. MAIN MEASUREMENTS: Predictable consultations (Pr): their
      content can be foreseen (check-ups, picking up results). Unpredictable
      consultations (Unp): we cannot predict their content (acute problems may arise
      unexpectedly). These include urgent consultations. Administrative consultations
      (Ad): bureaucratic tasks (prescriptions, repeat sick-notes, sick certificates).
      Care consultations (Car): prevention, diagnosis and treatment of the illness, or
      monitoring of it. Variables here are the patient, the doctor and the
      consultation. RESULTS: 60% (1809) (95% CI, 58.69%-61.59%) of the reasons were Pr
      and 40% (1199) (95% CI, 36.6%-43.12%) were Unp. 50% (1509) (95% CI, 47.26%
      53.06%) were Car, and 50% Ad (1499) (95% CI, 46.34%-53.39%). 40% (1189) (95% CI,
      37.78%-41.28%) were Pr-Ad and only 21% (620) (95% CI, 19.16%-22.06%) were Pr-Car.
      30% (889) (95% CI 27.92 %-31.18%) were Unp-Car, and 10% (310) (95% CI, 9.22%
      11.4%) Unp-Ad. 48% of patients with a single reason for attendance were Pr-Ad
      (577) (95% CI, 44.25%-52.05). Teaching centres and computerised ones had less Pr
      Ad load. Pr-Ad consultations increased with patient's age and with case-load.
      CONCLUSIONS: Almost 40% of the reasons for consultation are Pr-Ad, which implies
      inadequate clinical management. An intervention is needed to free up medical time
      consumed by bureaucratic questions, so that this time can be devoted fully to
      health-care tasks.

PMID- 14967124
TI  - [Patients over-using a primary care centre: their social, demographic and
      clinical characteristics, and their use of health service facilities].
AB  - OBJECTIVES: To find the social and clinical characteristics of patients over
      using (OUP) our centre. To find how much these patients use the health services.
      DESIGN: Observational, descriptive study. SETTING: Urban primary care centre (36
      408 inhabitants). PARTICIPANTS: Patients over 15 seen at the centre during the
      year 2000, who exceeded in their number of attendances the mean plus two standard
      deviations for their age group. MAIN MEASUREMENTS: The records of OUPS were
      reviewed to analyse their social and demographic characteristics, kinds of
      attendance, reasons for consultation, further tests, medication, referrals, and
      time off work this year. RESULTS: The sample was of 954 OUPs, 50.9% of whom were
      male with an average age of 50.54 (SD, 19.68). 86.3% had some risk factor
      recorded (34% hypertension, 32.4% mental health, 27.7% obesity, 25.7% tobacco
      dependency, 17.7% diabetes mellitus). They generated a mean of 9.6 visits to the
      doctor per year, with 95% CI (8.09-11.19), with the most common reason for
      attendance the monitoring of acute pathology (19.29%), followed by monitoring of
      chronic pathology (14.32%). There was an average of 1 analysis per OUP per year,
      and 0.68 image tests per OUP per year (48.38% were simple x-rays). 46.8% of the
      medication prescribed were analgesics. Average time off work was 0.5 periods off
      per OUP per year, with a mean period of 49.4 days off (SD, 113.69). They
      engendered an average of 4.15 nursing visits per OUP per year, 95% CI (2.60
      5.70), with monitoring of chronic pathology the most common reason for
      consultation. 30.3% of OUP had a visit to hospital casualty recorded, with osteo
      muscular pathology the most common reason for consultation (34.29%). Mean
      referrals were 0.88 OUP per year, with traumatology being the department to which
      most referrals were made (13.92%). CONCLUSIONS: OUP are middle-aged, have
      associated chronic pathology and use programmed appointments a lot. The
      additional tests conducted matched the centre's procedures for monitoring chronic
      pathologies. The most common reason for attendance at casualty was traumatology,
      as was the specialist clinic to which most referrals were made.

PMID- 14967125
TI  - [Citizens opinions, experiences and perceptions about waiting lists for elective
      cataract surgery and hip and knee replacement. ].
AB  - OBJECTIVES: The aim of this study is to describe the views, perceptions and
      personal experience around elective cataract and hip and knee replacement waiting
      lists in Catalonia in order to improve their management. DESIGN: Qualitative
      methodology: four focus groups for each procedure. PLACE: Conducted between
      February-March 2000 at the Catalan Health Services headquarters. PARTICIPANTS:
      Each focus group included consultants (ophtalmologists, orthopedic surgeons,
      rheumatologists, rehabilitators, GPs), other related health professionals
      (nurses, social workers, physiotherapists, opticians/optometrist, GPs), patients
      and relatives and general population. Participants were selected through
      researchers and the clinical scientific committees. All of them followed a pre
      established inclusion criteria. MAIN MEASURES: The analysis of the information
      was performed using the content analysis technique (contents of sessions were
      transcripted and information classified according to themes). RESULTS: Ten themes
      were identified. Waiting lists were argued to be a consequence of lack of
      resources, bad management and conflict of interest among consultants. Overall,
      the health care authority responsibility for the solution was acknowledged,
      although some participants claim more citizen participation. Among proposed
      solutions, prevention and education, more resources and improved management were
      found. Furthermore, a better physician-patient communication was considered
      essential. All the groups disagreed with the implicit current prioritisation
      system, however none wanted to assume the responsibility. CONCLUSIONS: Citizen's
      perceptions and personal experiences point to a multifactorial approach to
      waiting lists management, which would ameliorate the problem and lead to a better
      social acceptance.

PMID- 14967126
TI  - [The communications media and public opinion on health].

PMID- 14967127
TI  - [When to begin breast cancer care?].

PMID- 14967128
TI  - [Illness similar to serum sickness and bupropion].

PMID- 14967129
TI  - [Use of medication for osteoporosis in Spain].

PMID- 14967130
TI  - [Type-2 diabetes mellitus: does insulin therapy in primary care improve metabolic
      control?].

PMID- 14967131
TI  - [Dolichocolon as unwanted effect of treatment with the anti-depressant
      mirtazapine].

PMID- 14967132
TI  - [Has someone checked the data?].

PMID- 14967133
TI  - [GOLD: some considerations on its application in our primary care].

PMID- 14967135
TI  - [The home as the care centre in primary care].

PMID- 14967136
TI  - Teething with IKKalpha to make notches.
AB  - Sharpe and colleagues unveil a crucial role for NF-kappaB activity in tooth
      development, and show that IKKalpha functions both within and independently from
      the NF-kappaB pathway during molar and incisor morphogenesis, respectively (in
      the February issue of Developmental Cell).

PMID- 14967137
TI  - A protein interaction domain contacts RNA in the prespliceosome.
AB  - SR proteins bind to exons and recruit the spliceosome via protein interactions
      mediated by an arginine-serine-rich (RS) domain. In this issue of Molecular Cell,
      demonstrate that the RS domain of SR proteins contacts the pre-mRNA branchpoint,
      indicating that these domains participate in both protein and RNA interactions.

PMID- 14967138
TI  - The RITS complex-A direct link between small RNA and heterochromatin.
AB  - In a recent report, Moazed, Grewal, and colleagues (Verdel et al., 2004)
      characterize the RITS (RNA induced initiation of transcriptional silencing)
      protein complex in fission yeast. They provide a sought-for link between the
      small RNA produced by the RNA interference machinery and heterochromatin
      components, suggesting a mechanism for how heterochromatin formation can be
      targeted in trans to specific chromosomal regions.

PMID- 14967139
TI  - Repair of DNA covalently linked to protein.
AB  - A potentially lethal form of DNA/RNA modification, a cleavage complex, occurs
      when a nucleic acid-processing enzyme that acts via a transient covalent
      intermediate becomes trapped at its site of action. A number of overlapping
      pathways act to repair these lesions and many of the enzymes involved are those
      that catalyze recombinational-repair processes. A protein, Tdp1, has been
      identified that reverses cleavage-complex formation by specifically hydrolyzing a
      tyrosyl-DNA phosphodiester bond. The study of these pathways is both interesting
      and pertinent as they modulate the effectiveness of many antitumor/antibacterial
      drugs that act by stabilizing cleavage-complexes in vivo.

PMID- 14967140
TI  - Allosteric control of ligand selectivity between estrogen receptors alpha and
      beta: implications for other nuclear receptors.
AB  - Allosteric communication between interacting molecules is fundamental to signal
      transduction and many other cellular processes. To better understand the
      relationship between nuclear receptor (NR) ligand positioning and the formation
      of the coactivator binding pocket, we investigated the determinants of ligand
      selectivity between the two estrogen receptor subtypes ERalpha and ERbeta.
      Chimeric receptors and structurally guided amino acid substitutions were used to
      demonstrate that distinct "hot spot" amino acids are required for ligand
      selectivity. Residues within the ligand binding pocket as well as distal
      secondary structural interactions contribute to subtype-specific positioning of
      the ligand and transcriptional output. Examination of other NRs suggests a
      mechanism of communication between the ligand and coactivator binding pockets,
      accounting for partial agonist and dimer-specific activity. These results
      demonstrate the importance of long-range interactions in the transmission of
      information through the ligand binding domain as well as in determining the
      ligand selectivity of closely related NR receptor subtypes.

PMID- 14967141
TI  - JNK suppresses apoptosis via phosphorylation of the proapoptotic Bcl-2 family
      protein BAD.
AB  - JNK has been suggested to be proapoptotic, antiapoptotic, or have no role in
      apoptosis depending on the cell type and stimulus used. The precise mechanism of
      JNK action, under conditions when it promotes cell survival, is not entirely
      clear. Here, we report that JNK is required for IL-3-mediated cell survival
      through phosphorylation and inactivation of the proapoptotic Bcl-2 family protein
      BAD. IL-3 withdrawal-induced apoptosis is promoted by inhibition of JNK but
      suppressed by expression of a constitutively active JNK. JNK phosphorylates BAD
      at threonine 201, thereby inhibiting BAD association with the antiapoptotic
      molecule BCL-X(L). IL-3 induces BAD phosphorylation at threonine 201, and
      replacement of threonine 201 by alanine generates a BAD mutant, which promotes IL
      3 withdrawal-induced apoptosis. Thus, our results provide a molecular mechanism
      by which JNK contributes to cell survival.

PMID- 14967142
TI  - Shp2 regulates SRC family kinase activity and Ras/Erk activation by controlling
      Csk recruitment.
AB  - The protein-tyrosine phosphatase Shp2 plays an essential role in growth factor
      and integrin signaling, and Shp2 mutations cause developmental defects and/or
      malignancy. Previous work has placed Shp2 upstream of Ras. However, the mechanism
      of Shp2 action and its substrate(s) are poorly defined. Additional Shp2 functions
      downstream of, or parallel to, Ras/Erk activation also are proposed. Here, we
      show that Shp2 promotes Src family kinase (SFK) activation by regulating the
      phosphorylation of the Csk regulator PAG/Cbp, thereby controlling Csk access to
      SFKs. In Shp2-deficient cells, SFK inhibitory C-terminal tyrosines are
      hyperphosphorylated, and the tyrosyl phosphorylation of multiple SFK substrates,
      including Plcgamma1, is decreased. Decreased Plcgamma1 phosphorylation leads to
      defective Ras activation on endomembranes, and may help account for impaired Erk
      activation in Shp2-deficient cells. Decreased phosphorylation/activation of other
      SFK substrates may explain additional consequences of Shp2 deficiency, including
      altered cell spreading, stress fibers, focal adhesions, and motility.

PMID- 14967143
TI  - A membrane transport defect leads to a rapid attenuation of translation
      initiation in Saccharomyces cerevisiae.
AB  - Transport of lipids and proteins is a highly regulated process, which is required
      to maintain the integrity of various intracellular organelles in eukaryotic
      cells. Mutations along the yeast secretory pathway repress transcription of rRNA,
      tRNA, and ribosomal protein genes. Here, we show that these mutations also lead
      to a rapid and specific attenuation of translation initiation that occurs prior
      to the transcriptional inhibition of ribosomal components. Using distinct
      vesicular transport mutants and chlorpromazine, we have identified the eIF2alpha
      kinase Gcn2p and the eIF4E binding protein Eap1p as major mediators of the
      translation attenuation response. Finally, in chlorpromazine-treated cells, this
      response does not require Wsc1p or the protein kinase Pkc1p, both of which are
      upstream of the transcriptional repression of ribosomal components. Altogether,
      our results suggest that yeast cells not only evolved a transcriptional but also
      a translational control to assure efficient attenuation of protein synthesis when
      membranes are stressed.

PMID- 14967144
TI  - Arginine-serine-rich domains bound at splicing enhancers contact the branchpoint
      to promote prespliceosome assembly.
AB  - Exonic splicing enhancers (ESEs) are required for splicing of certain pre-mRNAs
      and function by providing binding sites for serine-arginine (SR) proteins, which
      contain an arginine-serine-rich (RS) domain. How an RS domain bound at the ESE
      promotes splicing is poorly understood. We have developed an RNA-protein
      crosslinking procedure to identify the target of the ESE-bound RS domain. Using
      this approach, we show that the ESE-bound RS domain specifically contacts the pre
      mRNA branchpoint. The interaction between the ESE-bound RS domain and the
      branchpoint occurs in the prespliceosome and is dependent upon the same splicing
      signals, biochemical factors, and reaction conditions required to support
      prespliceosome assembly. Analysis of RS domain mutants demonstrates that the
      ability to interact with the branchpoint, to promote prespliceosome assembly, and
      to support splicing are related activities. We conclude that the ESE-bound RS
      domain functions by contacting the branchpoint to promote prespliceosome
      assembly.

PMID- 14967145
TI  - A function of yeast mRNA cap methyltransferase, Abd1, in transcription by RNA
      polymerase II.
AB  - Capping enzymes bind the phosphorylated pol II CTD permitting cotranscriptional
      capping of nascent pre-mRNAs. We asked whether these interactions influence pol
      II function using ChIP in ts mutants of yeast capping enzymes. Pol II occupancy
      at the 5' ends of PGK1, ENO2, GAL1, and GAL10 was reduced by inactivation of the
      methyltransferase, Abd1, but not the guanylyltransferase, Ceg1, suggesting that
      Abd1 contributes to stable promoter binding. At other genes, Abd1 inactivation
      increased the 5':3' ratio of pol II density in the promoter-proximal region and
      caused Ser5 hyperphosphorylation of the pol II CTD. These results suggest an
      additional role for Abd1 in the promoter clearance and/or promoter-proximal
      elongation steps of transcription. The transcriptional functions of Abd1 are
      independent of methyltransferase activity. Manipulation of transcription by Abd1
      may enhance cotranscriptional capping and also act as a checkpoint to ensure that
      a nascent transcript has a cap before it can be completed.

PMID- 14967146
TI  - Association of Mre11p with double-strand break sites during yeast meiosis.
AB  - The repair of DNA double-strand breaks (DSBs) requires the activity of the
      Mre11/Rad50/Xrs2(Nbs1) complex. In Saccharomyces cerevisiae, this complex is
      required for both the initiation of meiotic recombination by Spo11p-catalyzed
      programmed DSBs and for break end resection, which is necessary for repair by
      homologous recombination. We report that Mre11p transiently associates with the
      chromatin of Spo11-dependent DSB regions throughout the genome. Mutant analyses
      show that Mre11p binding requires the function of all genes required for DSB
      formation, with the exception of RAD50. However, Mre11p binding does not require
      DSB formation itself, since Mre11p transiently associates with DSB regions in the
      catalysis-negative mutant spo11-Y135F. Mre11p release from chromatin is blocked
      in mutants that accumulate unresected DSBs. We propose that Mre11p is a component
      of a pre-DSB complex that assembles on the DSB sites, thus ensuring a tight
      coupling between DSB formation by Spo11p and the processing of break ends.

PMID- 14967147
TI  - The nuclease domain of adeno-associated virus rep coordinates replication
      initiation using two distinct DNA recognition interfaces.
AB  - Integration into a particular location in human chromosomes is a unique property
      of the adeno-associated virus (AAV). This reaction requires the viral Rep protein
      and AAV origin sequences. To understand how Rep recognizes DNA, we have
      determined the structures of the Rep endonuclease domain separately complexed
      with two DNA substrates: the Rep binding site within the viral inverted terminal
      repeat and one of the terminal hairpin arms. At the Rep binding site, five Rep
      monomers bind five tetranucleotide direct repeats; each repeat is recognized by
      two Rep monomers from opposing faces of the DNA. Stem-loop binding involves a
      protein interface on the opposite side of the molecule from the active site where
      ssDNA is cleaved. Rep therefore has three distinct binding sites within its
      endonuclease domain for its different DNA substrates. Use of these different
      interfaces generates the structural asymmetry necessary to regulate later events
      in viral replication and integration.

PMID- 14967148
TI  - Propagation of silencing; recruitment and repression of naive chromatin in trans
      by polycomb repressed chromatin.
AB  - The Polycomb group (PcG) proteins maintain stable and heritable repression of
      homeotic genes. Typically, Polycomb response elements (PRE) that direct PcG
      repression are located at great distances (10s of kb) from the promoters of PcG
      repressed genes, and it is not known how these PREs can communicate with
      promoters over such distances. Using Class II mouse PRC core complexes (mPCCs)
      assembled from recombinant subunits, we investigated how PcG complexes might
      bridge distant chromosomal regions. Like native and recombinant Drosophila Class
      II complexes, mPCC represses chromatin remodeling and transcription.
      Interestingly, mPCC bound to one polynucleosome template can recruit a second
      template from solution and renders it refractory to transcription and chromatin
      remodeling. A Drosophila PRC core complex (dPCC) also is able to recruit a second
      template. Posterior sex combs (PSC), a subunit of dPCC, inhibits chromatin
      remodeling and transcription efficiently but requires assembly with dRING1 to
      recruit chromatin. Thus, repression and template bridging require different
      subunits of PcG complexes, suggesting that long-range effects may be
      mechanistically distinct from repression.

PMID- 14967149
TI  - HP1 is essential for DNA methylation in neurospora.
AB  - Methylation of cytosines silences transposable elements and selected cellular
      genes in mammals, plants, and some fungi. Recent findings have revealed
      mechanistic connections between DNA methylation and features of specialized
      condensed chromatin, "heterochromatin." In Neurospora crassa, DNA methylation
      depends on trimethylation of Lys9 in histone H3 by DIM-5. Heterochromatin protein
      HP1 binds methylated Lys9 in vitro. We therefore investigated the possibility
      that a Neurospora HP1 homolog reads the methyl-Lys9 mark to signal DNA
      methylation. We identified an HP1 homolog and showed that it is essential for DNA
      methylation, is localized to heterochromatic foci, and that this localization is
      dependent on the catalytic activity of DIM-5. We conclude that HP1 serves as an
      adaptor between methylated H3 Lys9 and the DNA methylation machinery. Unlike
      mutants that lack DNA methyltransferase, mutants with defects in the HP1 gene hpo
      exhibit severe growth defects, suggesting that HP1 is required for processes
      besides DNA methylation.

PMID- 14967150
TI  - Proteasomal ATPases link ubiquitylation of histone H2B to methylation of histone
      H3.
AB  - In Saccharomyces cerevisiae, methylation of histone H3 at active genes is an
      epigenetic mark that distinguishes active from silent chromatin and functions as
      a short-term "memory" of recent transcription. Methylation of H3 at lysine
      residues K4 and K79 depends on ubiquitylation of histone H2B, but the mechanisms
      linking H2B ubiquitylation to H3 methylation are unknown. Here, we demonstrate
      that proteasomal ATPases Rpt4 and Rpt6 function to connect these two histone
      modifications. We show that recruitment of proteasome subunits to chromatin
      depends on H2B ubiquitylation and that mutations in Rpt4 and Rpt6 disrupt H3
      methylation at K4 and K79 but leave H2B ubiquitylation intact. Consistent with
      their role in H3 methylation, we also find that mutations in Rpt4 and 6-but not
      components of the 20S proteasome-disrupt telomeric gene silencing. These data
      reveal that proteasome subunits function in epigenetic gene regulation by linking
      chromatin modifications that establish the histone code.

PMID- 14967151
TI  - Bivalent tethering of SspB to ClpXP is required for efficient substrate delivery:
      a protein-design study.
AB  - SspB homodimers deliver ssrA-tagged substrates to ClpXP for degradation. SspB
      consists of a substrate binding domain and an unstructured tail with a ClpX
      binding module (XB). Using computational design, we engineered an SspB
      heterodimer whose subunits did not form homodimers. Experiments with the designed
      molecule and variants lacking one or two tails demonstrate that both XB modules
      are required for strong binding and efficient substrate delivery to ClpXP.
      Assembly of stable SspB-substrate-ClpX delivery complexes requires the coupling
      of weak tethering interactions between ClpX and the SspB XB modules as well as
      interactions between ClpX and the substrate degradation tag. The ClpX hexamer
      contains three XB binding sites, one per N domain dimer, and thus binds strongly
      to just one SspB dimer at a time. Because different adaptor proteins use the same
      tethering sites in ClpX, those which employ bivalent tethering, like SspB, will
      compete more effectively for substrate delivery to ClpXP.

PMID- 14967152
TI  - DHEAS as a new diagnostic tool.
AB  - Dehydroepiandrosterone sulfate (DHEAS) is a 19-carbon steroid, situated along the
      steroid metabolic pathway. It is the most abundant circulating steroid hormone in
      the body and can be converted to either androgens or estrogens. Their
      physiological and pathological functions have not yet been fully identified.
      Serum DHEAS concentrations peak at around age 25 years and then decline steadily
      over the following decades. Due to its long half-life and high concentration in
      the blood, the levels of DHEAS remain the same 24 h a day. This makes DHEAS a
      very interesting new diagnostic tool for both scientific research and clinical
      diagnostics. Moreover, circulating concentrations of DHEAS can be changed by many
      factors, such as endogenous production, hormone supplementation, many kinds of
      drugs, and many types of disease states. As research moves forward to better
      understand the relationships of DHEAS with health and disease, it is essential
      that studies should be designed to control for the influence of many factors on
      serum DHEAS concentrations.

PMID- 14967153
TI  - Haptoglobin polymorphism in breast cancer patients form Jordan.
AB  - BACKGROUND: Previous reports regarding the occurrence of breast cancer and its
      association with Hp polymorphism are conflicting. The possible role of family
      history as a factor in determining the degree of association between the disease
      and Hp polymorphism has not been reported before. In this study, the distribution
      of haptoglobin phenotype among patients with familial and nonfamilial breast
      cancer was investigated. METHODS: Haptoglobin phenotypes were determined in serum
      of 128 breast cancer patients (familial, n=42; nonfamilial, n=86) and in controls
      (n=200) by vertical polyacrylamide gel electrophoresis. RESULTS: No significant
      difference of Hp phenotype distribution was observed between patients as a
      combined group when compared with the control group. In the familial group, the
      frequency of Hp1-1 and Hp2-1 phenotype distribution was higher and Hp2-2 was
      lower than that in the nonfamilial and the control groups. Similar but inversed
      Hp distribution pattern was observed in the nonfamilial group when compared with
      that in the other groups. An appreciable finding is the observation that Hp2-2
      phenotype frequency in the nonfamilial group was significantly higher than that
      in the familial group (p=0.0365). CONCLUSIONS: Results of this study demonstrate
      that the pattern of Hp phenotype distribution in breast cancer patients is family
      history-dependent. Hp1 and Hp2 allele frequencies were over-represented in
      patients with familial and nonfamilial breast cancer, respectively. The pattern
      is probably attributed to genetic and oxidative stress mechanisms.

PMID- 14967154
TI  - Urinary alpha-ketoglutarate is elevated in patients with hyperinsulinism
      hyperammonemia syndrome.
AB  - BACKGROUND: Congenital hyperinsulinism (CHI) is the most frequent cause of
      recurrent episodes of hypoglycemia in infancy and results from different
      underlying genetic defects. The hyperinsulinism-hyperammonemia syndrome (HHS) has
      been shown to result from dominant germ line mutations within the glutamate
      dehydrogenase gene (GLUD1, OMIM *138130). Diagnosis of this entity is of clinical
      importance since invasive diagnostic procedures which are performed to identify
      focal pancreatic lesions are not necessary in HHS. Therefore, we investigated
      whether urinary concentration of alpha-ketoglutarate (alpha-KG) is elevated in
      patients with hyperinsulinism. METHODS: Excretion of alpha-KG was measured by gas
      chromatography/mass spectrometry (GC/MS) in eight patients with an activating
      GLUD1 mutation and 90 controls. RESULTS: Urinary alpha-KG was significantly
      elevated in seven of eight patients when compared to controls. Hyperammonemia was
      found in six of the eight patients with HHS. No relation was found between the
      underlying GLUD1 mutation and the level of urinary alpha-KG as well as the
      presence or absence of hyperammonemia. CONCLUSION: Urinary alpha-KG is elevated
      in most patients with HHS and should be included in the work-up of patients with
      hyperinsulinism.

PMID- 14967155
TI  - Fasting homocysteine levels in adults with type 1 diabetes and retinopathy.
AB  - BACKGROUND AND METHODS: Whether hyperhomocysteinemia is associated with diabetic
      retinopathy is still being debated. We measured homocysteine and thrombomodulin,
      a marker of endothelial cell damage, in patients with type 1 diabetes mellitus
      and retinopathy (n=25) and in a well-matched group of diabetic patients without
      retinopathy (n=23). All patients had normal serum creatinine and no
      macroalbuminuria. RESULTS: Fasting homocysteine levels were higher in the group
      with retinopathy than in the group without retinopathy (8.75+/-1.9 vs. 7.69+/-1.6
      micromol/l, P<0.05). Microalbuminuria was more prevalent in the group with
      diabetic retinopathy and it correlated with homocysteine levels in this group
      (p<0.05). Microalbuminuria was the most powerful independent determinant of
      homocysteine levels in multiple regression analysis in the group with retinopathy
      (p<0.01). Thrombomodulin levels were not different in the two groups (36.6+/-9.7
      vs. 34.9+/-11.1, p>0.1) and there was no correlation between homocysteine and
      thrombomodulin levels in either group. CONCLUSIONS: The slight rise in
      homocysteine levels in patients with diabetic retinopathy was possibly caused by
      the early nephropathy as indicted by microalbuminuria. This small rise in
      homocysteine levels was not associated with endothelial dysfunction, as measured
      by serum thrombomodulin levels.

PMID- 14967156
TI  - Validation of capillary glucose measurements to detect glucose intolerance or
      type 2 diabetes mellitus in the general population.
AB  - BACKGROUND: The use of an oral glucose tolerance test (OGTT) has been recommended
      to diagnose type 2 diabetes, but an OGTT with venous blood sampling may not be
      feasible in the screening phase preceding large epidemiological studies. We have
      conducted a population-based screening in 2715 men and women and evaluated the
      diagnostic validity of capillary plasma glucose concentration measurements versus
      venous plasma glucose concentration measurements in a subset of 350 subjects.
      METHODS: During a single OGTT, glucose concentrations were measured in venous
      plasma as well as in capillary plasma. RESULTS: Based on the 1999 WHO criteria
      for venous glucose concentrations, the study population (n=350) yielded 97
      subjects with type 2 diabetes mellitus, 77 subjects with impaired glucose
      tolerance and 176 subjects with normal glucose tolerance. Sensitivity and
      specificity to diagnose type 2 diabetes mellitus by capillary plasma were 84% and
      98%, respectively. Consistent classification by either venous or capillary plasma
      glucose measurements was 78% (kappa=0.65, p<0.001). CONCLUSION: Capillary glucose
      measurements are suitable for use in epidemiological studies to diagnose and
      detect type 2 diabetes and normal glucose tolerance. Use of capillary
      measurements can result in cost-effective inclusion schemes in epidemiological
      studies.

PMID- 14967157
TI  - Head-to-head comparison of the diagnostic utility of BNP and NT-proBNP in
      symptomatic and asymptomatic structural heart disease.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) and the amino-terminal fragment of
      the BNP prohormone (NT-proBNP) are markers for functional cardiac impairment and
      are elevated in heart failure (HF). Aim of the present study was to perform a
      head-to-head comparison of the diagnostic utility of BNP and NT-proBNP in
      symptomatic and asymptomatic structural heart disease. METHODS: We prospectively
      classified 180 consecutive subjects according to ACC/AHA guidelines. Blood
      concentrations of BNP and NT-proBNP were determined by two fully automated
      chemiluminescent assays (Bayer and Roche method). Diagnostic utilities were
      tested by ROC analyses and logistic regression. RESULTS: ROC curves of BNP and NT
      proBNP in patients with symptomatic HF (n=43) and asymptomatic subjects (n=137)
      did not differ significantly (AUC 0.930 vs. 0.918, p=0.650), but comparison of
      patients with asymptomatic structural heart disease (n=56) and subjects without
      structural disorder of the heart (n=81) revealed different AUCs for the
      respective assays (0.735 vs. 0.839, p=0.009). In the population studied, age, sex
      and renal function had no impact on the diagnostic performance of both tests when
      compared by logistic regression models. CONCLUSIONS: Both assays facilitate
      diagnosis of symptomatic and asymptomatic structural heart disease. BNP and NT
      proBNP may be equally useful as an aid in the differential diagnosis of probable
      signs or symptoms of HF. In contrast, NT-proBNP might be a more discerning marker
      of early cardiac dysfunction than BNP.

PMID- 14967158
TI  - A multiplexed allele-specific polymerase chain reaction assay for the detection
      of common thiopurine S-methyltransferase (TPMT) mutations.
AB  - BACKGROUND: Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of
      thiopurine drugs that are commonly used to treat a wide range of conditions. It
      is now well established that interpatient variation in sensitivity to these drugs
      is due to point mutations in the TPMT gene. The mutant alleles TPMT*2 (238G>C),
      TPMT*3A (460G>A, 719A>G), TPMT*3B (460G>A), and TPMT*3C (719A>G) account for 80
      95% of TPMT deficiency observed in Caucasian populations. In this paper, we
      describe a novel, multiplex, allele-specific polymerase chain reaction (PCR)
      method that detects the 238G>C, 460G>A, and 719A>G mutations, allowing for the
      simultaneous identification of TPMT*2 and TPMT*3 alleles. The assay is internally
      controlled, robust, and does not require the use of restriction endonucleases.
      Therefore, the assay is not prone to erroneous readings due to incomplete
      restriction digestion, as documented for existing PCR restriction fragment length
      polymorphism (RFLP) assays of TPMT.

PMID- 14967159
TI  - Supplementation with antioxidants in the treatment of Graves' disease; the effect
      on glutathione peroxidase activity and concentration of selenium.
AB  - BACKGROUND: The effect of supplementation with a fixed combination of
      antioxidants (vitamins C and E, beta-carotene and selenium) was monitored on the
      speed of attaining euthyroidism in a group of patients with Graves' disease,
      treated with methimazole. METHODS: The activity of glutathione peroxidase in
      whole blood and the concentrations of selenium, pituitary and thyroid hormones in
      serum were measured, prior to commencement of therapy and after 30 and 60 days.
      RESULTS Patients who received supplementation with antioxidants in addition to
      therapy with methimazole (Group A, n=29) attained euthyroidism faster than the
      patients treated with only methimazole (Group B, n=28). The concentration of
      selenium in the serum of patients in Group A increased significantly during
      treatment (p<0.001), while there was no statistically significant change in the
      patients in Group B. The concentration of selenium in the serum between the
      groups differed statistically significantly 30 days (p<0.05) and 60 days (p<0.01)
      after the commencement of therapy. Activity of glutathione peroxidase in whole
      blood increased during treatment in both groups of patients. However, a
      statistically more significant increase occurred in Group A compared to Group B,
      30 days after the commencement of therapy (p<0.01). CONCLUSION: The results of
      the study clearly indicate that supplementation with antioxidants in the
      treatment of Graves' disease is justified, particularly those containing
      selenium.

PMID- 14967160
TI  - Standardization of immunoassays for measurement of myoglobin in serum. Phase I:
      evaluation of candidate secondary reference materials.
AB  - BACKGROUND: Myoglobin is a low-molecular weight protein present in the cytosol of
      striated muscles. Its concentrations in serum can be measured by immunoassays and
      are used as an early indicator of myocardial necrosis. Since variability among
      commercial myoglobin assays exists, standardization of myoglobin assays is
      needed. METHODS: An international collaborative study was organized with the
      involvement of seven companies using 12 different automated platforms for
      measuring myoglobin. Five candidate secondary, i.e., matrixed, reference
      materials were assayed in relation to linearity, imprecision, recovery rate and
      commutability to demonstrate a possible identity between the materials and the
      usual routine serum samples. RESULTS: One lyophilized candidate material (human
      heart myoglobin in human serum) was selected as the most suitable secondary
      reference material, based on the criteria examined. Used as a calibrator a
      posteriori, the bias between the various myoglobin assays for a frozen human
      serum pool was reduced from 32% to 13%. CONCLUSION: This study provides the basis
      for the selection of an internationally recognized secondary reference material.

PMID- 14967161
TI  - The uristatin dipstick is useful in distinguishing upper respiratory from urinary
      tract infections.
AB  - BACKGROUND: We determined the diagnostic value of the trypsin inhibitor,
      uristatin, that is commonly found in urine and plasma in patients with infections
      or inflammations of any kind. METHODS: We collected urine specimens from patients
      with infections of the urinary or upper respiratory tract and from healthy
      controls. We also collected blood from patients with a likely upper respiratory
      tract infection and healthy controls. A bacterial count of >10(5) organisms/ml in
      urine was considered to represent infection rather than contamination. RESULTS:
      The uristatin dipstick test in urine showed acceptable negative predictive values
      (NPV of up to 93%) for patients without infection or inflammation. Here, the
      dipsticks could eliminate some urine cultures. For those with infection or
      inflammation, the positive predictive values (PPV) of the dipsticks were lower
      (up to 57%). Including the leukocyte esterase and nitrite values increased the
      PPV of the dipsticks for those with disease. CONCLUSIONS: The uristatin strip was
      more accurate than the leukocyte and nitrite dipsticks for predicting upper
      respiratory infections (URI) and C-reactive protein for those with infection or
      inflammation. The uristatin dipstick was able to detect both the bikunin and
      uristatin inhibitors.

PMID- 14967162
TI  - Nitric oxide-induced apoptosis is mediated by Bax/Bcl-2 gene expression,
      transition of cytochrome c, and activation of caspase-3 in rat vascular smooth
      muscle cells.
AB  - BACKGROUND: In contrast to the anti-apoptotic action of nitric oxide (NO) on
      endothelial cells, NO exerts a pro-apoptotic effect on vascular smooth muscle
      cells (VSMCs). This study was designed to elucidate the mechanism underlying NO
      induced apoptosis in rat VSMCs. METHODS AND RESULTS: (1) Using the terminal
      deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling
      (TUNEL) assay and fluorescence activated cell sorter (FACS) analyses, apoptosis
      of rat VSMCs were confirmed after exposure to sodium nitroprusside (SNP) (0.5 to
      4 mmol/l), an exogenous NO donor. The effects of SNP were blocked by hemoglobin.
      (2) A universal caspase inhibitor, z-VAD-fmk, dose-dependently inhibited NO
      induced apoptosis. VSMCs degraded Ac-DEVD-pNA rather than Ac-WHED-pNA after
      exposure to SNP, which suggested that the activation of caspase 3 rather than
      caspase 1 was involved in the process. Immunoblot analysis confirmed the
      activation of caspase-3. (3) Exposure to SNP induced the release of cytochrome c
      from the mitochondria to the cytosol, which was detected by immunoblot analysis
      of mitochondrial and cytosol fractions. (4) SNP exposure increased the ratio of
      Bax/Bcl-2 protein expression twofold by immunoblot analysis. CONCLUSIONS: The
      mechanism of NO-induced apoptosis in rat VSMCs involves an increase in the ratio
      of Bax/Bcl-2 gene expression, which leads to the release of cytochrome c from the
      mitochondria to the cytosol, finally activating caspase-3 and resultant
      apoptosis.

PMID- 14967163
TI  - Real-time PCR-based genotyping assay for CXCR2 polymorphisms.
AB  - BACKGROUND: The human chemokine receptor CXCR2 (IL8RB) is a high affinity
      receptor for interleukin-8 as well as other CXC chemokines, and is involved in
      the chemotaxis of immune cells. Genetic variants of CXCR2 have potential
      relevance in various inflammatory human disorders. We developed a real-time
      polymerase chain reaction (PCR)-based allelic discrimination assay for the
      detection of the CXCR2 single nucleotide polymorphisms (SNPs) C785T, T1208C and
      G1440A. METHODS: Polymorphisms were delineated using PCR amplification of
      specific alleles (PASA). Allele-specific primers were developed for both wild
      type and mutant alleles. An additional nucleotide mismatch at the third position
      from the 3' end of each primer was used to improve amplification specificity and
      to prevent generation of nonspecific products. Genotypes were assigned based on
      PCR growth curves and melt curve analysis performed on a SmartCycler using SYBR
      Green I chemistry. RESULTS: Genotyping assignments were successfully performed in
      a set of 20 human DNA samples, and were validated by comparison with results from
      direct DNA sequencing and agarose gel electrophoresis of PCR products.
      CONCLUSIONS: Due to its rapid and relatively inexpensive performance and
      accuracy, the presented allelic discrimination assay for CXCR2 polymorphisms has
      wide applicability, especially for high-throughput sample analysis in large
      population genotyping studies.

PMID- 14967164
TI  - Diagnostic value of pleural fluid adenosine deaminase activity in tuberculous
      pleurisy.
AB  - BACKGROUND: Diagnosis of tuberculous pleuritis is difficult because of its
      nonspecific clinical presentation and insufficient efficiency of traditional
      diagnostic methods. We investigated the use of adenosine deaminase (ADA) activity
      in tuberculous pleuritis diagnosis. METHODS: We optimized a kinetic assay and
      retrospectively analysed 210 patients with exudative pleural effusions. Using the
      ROC curve, we determined the optimal cutoff for TB pleurisy. RESULTS: One hundred
      forty-seven exudative samples were nontuberculous (non-TB) and 63 were
      tuberculous (TB). There was statistically significant difference (p<0.0001)
      between the means of pleural fluid ADA levels among the TB and non-TB
      populations. The disease prevalence of TB pleurisy in the studied population was
      30%. The cutoff value for diagnosing TB effusions was >55.8 U/L, with a
      sensitivity of 87.3% (95% CI: 76.5-94.3%) and specificity of 91.8% (95% CI: 86.2
      95.7%). The positive predictive value (PPV) was 82.1% and the negative predictive
      value (NPV) was 94.4%. A pleural fluid ADA value <16.81 IU/L suggests that a
      tuberculous effusion is highly unlikely (100% sensitive with 100% NPV and 0%
      negative likelihood ratio for a pleural fluid ADA level>/=16.81 U/L). In
      addition, the area under the ROC curve was 0.933 (S.E.=0.0230, 95% CI: 0.890
      0.963). CONCLUSION: Pleural fluid total ADA assay is a sensitive and specific
      test suitable for rapid diagnosis of TB pleurisy.

PMID- 14967165
TI  - Noncompetitive enzyme immunoassay for carcinoembryonic antigen by flow injection
      chemiluminescence.
AB  - BACKGROUND: Recently, many automated immunoassay analyzers have been developed
      for carcinoembryonic antigen (CEA) to overcome the shortcomings in traditional
      immunoassay methods that are time-consuming and labor-intensive. Flow injection
      immunoassay (FIIA) has been increasingly applied to laboratory medicine due to
      its ease in automation, rapid speed and reproducible results. It is important to
      develop a FIIA method for CEA determination. METHODS: Based on a noncompetitive
      immunoassay format, a CEA-immobilized immunoaffinity column inserted in the flow
      system was used to trap the unbound horseradish peroxidase (HRP)-labeled antibody
      after an off-line incubation of CEA and HRP-labeled anti-CEA. The trapped enzyme
      conjugate was detected by injecting substrates to produce an enhanced
      chemiluminescence (CL). RESULTS: The linear range for CEA was 1.0-25 ng/ml with a
      correlation coefficient of 0.997 and a detection limit of 0.5 ng/ml. The sampling
      and chemiluminescence detection time for one sample was 5 min after a
      preincubation procedure of 25 min. Twenty five human serum samples detected by
      this method were in good agreement with the results obtained by immunoradiometric
      assay (IRMA). CONCLUSIONS: This method could be used for rapid analysis of CEA
      and potentially other antigens.

PMID- 14967166
TI  - Influences of hypercholesterolemia on red cell indices and erythrocyte
      sedimentation rate in elderly persons.
AB  - BACKGROUND: We investigated whether hypercholesterolemia influenced the values of
      mean corpuscular volume (MCV) and erythrocyte sedimentation rate (ESR). METHODS:
      A total of 463 nonanemic elderly persons were evaluated regarding red cell
      indices, ESR, and ESR-related parameters, such as fibrinogen, albumin, and C
      reactive protein (CRP). RESULTS: There were no significant differences in MCV
      between elderly men with and without hypercholesterolemia (>/=240 mg/dl) nor
      between the subjects with a marked increase of serum cholesterol concentrations
      (>/=260 mg/dl) and with severely lowered cholesterol concentrations (<155 mg/dl).
      ESR in elderly men with hypercholesterolemia averaged 12.3+/-6.8 mm/h, which were
      significantly higher than in those without hypercholesterolemia (6.0+/-4.7 mm/h,
      p<0.01). ESR averaged threefold higher in the elderly men with serum cholesterol
      concentration >/=260 mg/dl versus those with serum cholesterol concentrations
      <155 mg/dl, although no significant differences were observed in fibrinogen,
      albumin, and CRP values between the two groups. Serum cholesterol concentrations
      were higher in elderly men with ESR>/=15.0 mm/h (248.9+/-43.5 mg/dl), compared to
      those with ESR<2.0 mm/h (199.5+/-31.7 mg/dl, p<0.01). Serum cholesterol
      concentrations showed no associations with red cell indices but correlated
      significantly with ESR in elderly men (r=0.24, p<0.01) and postmenopausal women
      (r=0.21, p<0.01). CONCLUSION: Hypercholesterolemia does not appear to influence
      MCV but significantly accelerates ESR, especially in elderly men.

PMID- 14967167
TI  - Determination of plasma prothrombin levels by a novel Ca2+-dependent prothrombin
      activator (CA-1) in patients with chronic liver diseases.

PMID- 14967168
TI  - The association between preeclampsia and angiotensin-converting enzyme
      insertion/deletion polymorphism.
AB  - BACKGROUND: Plasma and tissue angiotensin-converting enzyme (ACE) activities are
      believed to be under genetic control. Increased ACE activity due to the deletion
      polymorphism of the ACE gene is associated with a wide variety of diseases that
      exhibit endothelial disturbances. Available reports suggest that the incidence of
      ACE gene deletion polymorphism associated with preeclampsia varies depending on
      the study population and geographic location. In this study, we examined the
      insertion/deletion genotype distribution and the activity of ACE in preeclamptic
      pregnants. METHODS: Ninety-five preeclamptic and 50 normotensive pregnant
      patients, both in their third trimester, as well as 39 healthy nonpregnant
      individuals were included in the study. Gene polymorphism was studied by the
      polymerase chain reaction followed by the agarose electrophoresis. Pearson's
      chi(2) test was used for the statistical evaluation of the allele frequency, and
      Student's t-test for the ACE activity. RESULTS: The presence of D allele was
      found to be associated with preeclampsia (p<0.05, odds ratio=1.53; df=1; 95%
      CI=1.007-2.338). The influence of allelic distribution on the enzyme activity was
      observed in the preeclamptics bearing II genotype, who exhibited significantly
      lower activity of ACE than that of the patients with the other genotypes
      (p<0.05). CONCLUSION: We found an association between the genotype II and low ACE
      activity in preeclamptic women and an association between D allele frequency and
      preeclampsia. Pregnancy alone did not have an effect on the ACE activity.

PMID- 14967169
TI  - Increased cystatin C serum concentrations in patients with hepatic diseases of
      various severities.
AB  - BACKGROUND: Indicators for long-term monitor of the progress of hepatic diseases
      are of great clinical importance. Since elevated cathepsin was observed in liver
      diseases, the aim of this study is to investigate the involvement of cystatin C,
      a very potent inhibitor of cathepsin and a recently introduced marker for renal
      function, and to see the applicability of serum cystatin C being a convenient
      marker for the progression of liver diseases. METHODS: One hundred eighty
      consecutive patients with chronic liver disease of various severities and 45
      healthy controls were recruited to determine their serum cystatin C
      concentrations by N Latex Cystatin C kit, as well as certain relevant clinical
      values, including alanine transaminase (ALT), aspartate transaminase (AST) and
      AFP. RESULTS: Average serum cystatin C concentration of patients with hepatic
      diseases was significantly higher than that of control (0.0902+/-0.0025 mg/dl vs.
      0.067+/-0.007 mg/dl; p<0.001), and a linear regression analysis has revealed a
      direct relation between cystatin C and the severity of liver diseases
      (Y=1.172+5.492X, R(2)=0.088, p<0.001). CONCLUSION: This study suggested that
      cystatin C may be an applicable monitoring marker for monitoring liver functions
      and progression of liver fibrosis.

PMID- 14967170
TI  - Uric acid and allantoin levels in Down syndrome: antioxidant and oxidative stress
      mechanisms?
AB  - BACKGROUND: Down syndrome (DS) is a chromosomal abnormality (trisomy 21) leading
      to mental retardation, to the characteristic change of individual's phenotype and
      to the pathological features of Alzheimer disease. Patients with DS have elevated
      ratio of superoxide dismutase to (catalase plus glutathione peroxidase) with
      respect to controls in all age categories suggesting that oxidative imbalance
      contributes to the clinical manifestation of accelerated aging. RESULTS: We
      report that persons with DS have elevated uric acid levels compared with
      controls, 348.56+/-22.78 versus 284.00+/-20.86 micromol/l (p=0.018). The levels
      of hypoxanthine and xanthine in DS children (6.35+/-0.31 and 1.02+/-0.23
      micromol/l) were significantly lower than in controls (7.83+/-0.59 and 2.43+/
      0.66 micromol/l). This result suggests increased conversion of hypoxanthine and
      xanthine to uric acid with subsequent free radical-dependent oxidation of uric
      acid to allantoin, mechanisms potentiated by the oxidative stress in DS.
      Allantoin is a nonenzymatic oxidative product of uric acid in human. In DS
      individuals, the levels of allantoin were significantly higher than those in
      healthy controls (18.58+/-2.27 and 14.07+/-1.07 micromol/l, respectively,
      p=0.03). CONCLUSIONS: Our data supported the presumption of increased oxidative
      stress in DS.

PMID- 14967171
TI  - Low-molecular-weight dextran sulfate prevents experimental urolithiasis in rats.
AB  - BACKGROUND: Low-molecular-weight dextran sulfate was tested on an experimental
      model of urolithiasis induced in rats. METHODS: Male Wistar rats weighing 250 g
      had a 15-mg calcium oxalate stone surgically placed into the bladder. A group was
      sham operated, another group was treated by daily intraperitoneal injection of
      low-molecular-weight dextran sulfate and the other by daily intraperitoneal
      saline injection. RESULTS: This treatment prevents the growth of exogenous
      calcium oxalate stone introduced into the bladder and also avoided the formation
      of secondary stones in the animals. In addition, low-molecular-weight dextran
      sulfate prevented the aggregation of other ions, such as ammonium, phosphate and
      magnesium to the calcium oxalate stone placed in the bladder. These effects of
      the low-molecular-weight dextran sulfate are associated with the presence of the
      sulfated polysaccharide in the urine. However, the polysaccharide did not adhere
      to the bladder stone. Possibly, dextran sulfate forms soluble complex with
      calcium ions dissolved in the urine and therefore prevented calcium salt
      crystallization. CONCLUSION: Dextran sulfate, 8000 Da, led to a decrease in
      calculi glycosaminoglycans in animals treated with dextran, and there was an
      inhibition in bladder-implanted stones growth.

PMID- 14967172
TI  - The effect of the steroid-sparing response to low-dose methotrexate on bone
      metabolism in glucocorticoid-dependent asthmatics.
AB  - BACKGROUND: The skeletal effects of low-dose methotrexate (MTX), in
      glucocorticoid-dependent asthmatics (GCDA), are unknown. METHODS: We studied 9
      patients from a total of 26 chronic GCDA who completed 28 weeks of MTX (15 mg
      weekly, intramuscularly). Prednisolone dose was not altered during the first 12
      weeks, and was then reduced between 12 and 28 weeks. Mean (S.E.M.) age of the
      patients was 54 (4.0) years. They had normal bone mineral density (BMD), were not
      taking medication that affected bone metabolism (except prednisolone and inhaled
      corticosteroids) and all achieved at least 50% reduction in prednisolone dose at
      28 weeks. Blood and urine samples were obtained at baseline, 12, 28 and 40 weeks
      for measurement of serum osteocalcin (OC) and bone alkaline phosphatase (Bone
      ALP) as formation markers and urinary deoxypyridinoline (DPD) and N-terminal
      cross-linked telopeptide of type I collagen (NTX-I) as resorption markers.
      RESULTS: Concurrently with the changes in prednisolone dosage serum OC levels
      increased significantly at 28 weeks (p<0.008) (8.1+/-1.0 ng/ml) compared to
      baseline (4.7+/-0.6 ng/ml) and 12 weeks (5.1+/-0.6 ng/ml), but trended back by 40
      weeks (6.6+/-0.6 ng/ml). No significant changes were observed for the other bone
      markers between baseline and the other time points. CONCLUSIONS: The beneficial
      effects of steroid reduction on bone metabolism do not appear to be impaired by
      concomitant MTX treatment at least over 12 weeks.

PMID- 14967173
TI  - Blood lactoferrin release induced by running exercise in normal volunteers:
      antibacterial activity.
AB  - BACKGROUND: The aim of this study was to determine serum lactoferrin
      concentrations and serum antibacterial activity before and after running
      exercise. METHODS: Twenty-four healthy young men were randomly assigned to high,
      middle, or low intensity of exercise groups (5000 steps running at 180, 130, and
      80 steps/min, respectively). Blood samples were collected at baseline and
      immediately, 1 and 4 h after exercise. Concentrations of circulating neutrophils,
      serum lactoferrin, iron in whole blood, and serum iron were measured.
      Antibacterial activity of serum was evaluated using live Micrococcus luteus.
      RESULTS: The numbers of circulating neutrophils were increased by 20.0% and 15.5%
      1 h after exercise in high and middle groups (both P<0.01), respectively. Serum
      lactoferrin concentrations were significantly increased immediately after
      exercise by 48.3% and 33.0% in the high and middle groups (both P<0.01),
      respectively. No significant changes in total iron or serum iron concentrations
      were observed during the study. Antibacterial activities of serum collected
      immediately after exercise in the high and middle groups were significantly
      stronger than those before exercise, by 31.2% and 25.4% (both P<0.05),
      respectively. CONCLUSIONS: Serum lactoferrin concentrations are increased
      immediately after running exercise and may play an antibacterial role in host
      defenses before mobilization of neutrophils into the circulating pool.

PMID- 14967174
TI  - Measurement of reduced and oxidized coenzyme Q9 and coenzyme Q10 levels in mouse
      tissues by HPLC with coulometric detection.
AB  - BACKGROUND: Ubiquinone-responsive multiple respiratory chain dysfunction due to
      coenzyme Q(10) (CoQ(10)) deficiency has been previously identified in muscle
      biopsies. However, previous methods are unreliable for estimating CoQ(10) redox
      status in tissue. We developed an accurate method for measuring tissue
      concentrations of reduced and oxidized coenzyme Q (CoQ). METHODS: Mouse tissues
      were weighed in the frozen state and homogenized with cold 1-propanol on ice.
      After solvent extraction, centrifugation and filtration, the filtrate was
      subsequently analyzed by reversed-phase HPLC with coulometric detection. RESULTS:
      Reference calibration curves were used to determine reduced and oxidized coenzyme
      Q(9) (CoQ(9)) and CoQ(10) concentrations in tissues. The method is sensitive (
      approximately 15 microg/l), reproducible (6% CV) for CoQ(9) and CoQ(10), and
      linear up to 20 mg/l for CoQ(9) and CoQ(10). Analytical recoveries were 90-104%.
      In mouse tissues the amounts of total CoQ (TQ) ranged from 261 to 1737 nmol/g of
      protein. Total CoQ(9) levels are comparable with the values of those previously
      reported. CoQ is found to be mostly in the reduced form in mouse liver (
      approximately 87%), heart ( approximately 60%), and muscle tissues (
      approximately 58%); in the brain, most of the CoQ is in the oxidized state (
      approximately 65%). CONCLUSION: This procedure provides a precise, sensitive, and
      direct assay method for the determination of reduced and oxidized CoQ(9) and
      CoQ(10) in mouse hindleg muscle, heart, brain, and liver tissues.

PMID- 14967175
TI  - Membrane lipids and protein-bound carbohydrates status during the maturation of
      reticulocytes to erythrocytes in type 2 diabetics.
AB  - BACKGROUND: The reticulocyte maturation process is an ideal model for the study
      of biochemical alterations seen during final stage of erythropoiesis under
      disease conditions. In this study, determined whether type 2 diabetes has any
      effect on membrane lipids and protein-bound carbohydrates during the maturation
      of reticulocytes to erythrocytes. SUBJECTS AND METHODS: Lipids (cholesterol and
      phospholipids) and protein-bound carbohydrates (hexose, hexosamine and sialic
      acid) were extracted and estimated in plasma, membrane of reticulocytes and
      erythrocytes from 20 treated but uncontrolled type 2 diabetic volunteers and age
      matched controls. RESULTS: Plasma, membranes of reticulocytes and erythrocytes of
      diabetics showed increase in cholesterol (35.7%, 8.7% and 16.4%); phospholipids
      (43.4%, 18.8% and 8.2%); hexose (34.1%, 19.3% and 8.2%) and decrease in
      hexosamine (11.9%, 7.3% and 14.7%); and sialic acid (34.1%, 19.3% and 32.0%)
      compared to controls. As reticulocytes matured to erythrocytes, cholesterol,
      phospholipids, hexosamine and sialic acid levels were decreased; C/P ratio and
      hexose levels were increased in both controls and diabetics. However, these
      alterations were more intensified in diabetics. CONCLUSION: These alterations in
      diabetic patients may indicate the existence of one or both of the following
      conditions: acceleration of maturation processes and/or decreased red blood cell
      life span.

PMID- 14967176
TI  - The level of antioxidant enzymes, plasma vitamins C and E in cement plant
      workers.
AB  - BACKGROUND: Chronic exposure to cement dust has been reported to lead to several
      health problems. This study was designed to investigate the plasma oxidant and
      antioxidant status in cement plant workers and control subjects. METHODS: Twenty
      eight volunteer male cement plant workers and 30 volunteer office male workers
      (control) aged 29-54 years participated. The concentration of plasma vitamin C (P
      VC), plasma vitamin E (P-VE), plasma malondialdehyde (P-MDA), and the activity of
      erythrocyte superoxide dismutase (E-SOD), plasma glutathione peroxidase (P-GSH
      Px), and some serum biochemical parameters were measured in both groups. RESULTS:
      The levels of MDA (175%), ALT (61%), and AST (39%) were significantly increased,
      while total RBC count (12%), Hb (11%) vitamin E (51%), C (35%), SOD (44%), and
      GSH-Px (51%) activities were markedly decreased, and the levels of urea, protein,
      and albumin triglyceride and cholesterol were almost the same in cement plant
      workers versus the control subjects. CONCLUSION: Cement workers are exposed to
      more oxidative stress compared to control subjects. To overcome these oxidative
      stresses, supplementation of antioxidant vitamins, such as alpha-tocopherol and
      ascorbic acid, may be beneficial. In addition, proper precaution to protect
      workers could prevent serious health problems.

PMID- 14967177
TI  - Charge variants in serum and urine hCG.
AB  - BACKGROUND: All serum and urine pregnancy tests sold in the United States are
      calibrated against the WHO 3rd and 4th International Standards (3rd and 4th I.S.)
      of Human Chorionic Gonadotropin (hCG). These standards have been isolated from
      pregnancy urine; however, they are used to calibrate, and generate antibodies
      used in both urine and serum hCG tests. hCG molecules may vary in sialic acid
      content; this changes the acidity of the molecule. Published studies have shown
      that these carbohydrate elements may alter recognition of hCG in different serum
      and urine hCG tests. We investigated the charge variants of hCG in serum and
      urine samples, and in hCG standards. METHODS: Samples were analyzed by
      preparative isoelectric focusing. Charge variants of hCG were quantitated using
      the DPC Immulite hCG assay. RESULTS: A difference was observed in the proportion
      of charge variants in urine and serum samples. There was a significantly higher
      proportion of more-acidic variants in the urine samples. CONCLUSIONS: Urine
      derived standards may not be representative of serum hCG and therefore may not be
      appropriate for calibrating serum assays. Variation among hCG test results when
      using different immunoassays has been a persistent problem for years. Additional
      studies are needed to focus on the molecular dissimilarity of urine and serum
      hCG, as well as other factors, to determine their significance and contribution
      to the problem of interassay variation when comparing hCG results.

PMID- 14967178
TI  - Composition of urinary glycosaminoglycans in a patient with juvenile hyaline
      fibromatosis.

PMID- 14967179
TI  - Nutritional status of older people in long term care settings: current status and
      future directions.
AB  - Despite being preventable and treatable, in the 21st Century, malnutrition
      remains a problem in the developed world and the nutritional needs of many older
      people in long-term care settings are not met. The UK government has pledged to
      provide high-quality care for this sector of the population, including minimum
      standards to ensure adequate nutrition. However, research is still needed into
      the detection, prevalence, cause and effects of malnutrition and maintenance of
      optimum nutrition; and to address the lack of training and education among those
      caring for older peoples. In the interim, simple measures such as monitoring
      older people's weight regularly need to be implemented as a surveillance measure
      of nutritional status.

PMID- 14967180
TI  - Lived experience of Korean women suffering from rheumatoid arthritis: a
      phenomenological approach.
AB  - Rheumatoid arthritis (RA) sufferers number approximately 200 million people
      around the world. In Korea, there is no accurate statistical information, but 1
      2% of the total population have been estimated to be suffering from RA. Current
      research studies related to RA have been limited to quantitative approaches. In
      qualitative studies, most research has been focused on one aspect of the
      experience of patients with RA, such as pain or fatigue. In order to address the
      problems of patients with chronic disease, like RA, a comprehensive approach
      should be demanded concerning various aspects of the patient's life in terms of
      perspectives of the patients with RA. The purpose of this study was to explore
      and describe the illness experience of women with RA in Korea using a
      phenomenological methodology. Participants were five women who were diagnosed
      with RA. The transcripts were analyzed using Colaizzi's (In: Vails, R.S., King,
      M. (Eds.), Existential Phenomenological Alternatives for Psychology. Oxford
      University Press, New York, 1978) method. The results of this study identified 8
      major theme clusters, which were 'severe pain', 'self-esteem', 'negative
      feelings', 'reflect the past life', 'concentrate on recovery from disease', 'a
      comfortable mind in pain', 'support of family and others', and 'new life'. These
      results may provide important information to establish effective interventions
      for women with RA, their families, and health providers through understanding
      various aspects of the lived experience of women with RA. The implications for
      nursing practice in this area of chronic illness such as RA, should be how
      patients can be empowered to believe they can take control of their disease and
      their lives.

PMID- 14967181
TI  - Five-year follow-up study of stress among nurses in public and private hospitals
      in Thailand.
AB  - A longitudinal perspective on 14 hospitals in Thailand examined sources of
      occupational stress, coping strategies, and job satisfaction. A sample of 200
      nurses was compared to 147 nurses sampled from the same hospital wards after 5
      years and revealed a significant increase in nurses' workload, involvement with
      life and death situations, and pressure from being required to perform tasks
      outside of their competence. Although nurses working in public hospitals
      generally reported more stress than private hospitals, surprisingly nurses'
      satisfaction with their job increased particularly in public hospitals, which may
      be attributable to age, improvements in monetary compensation, and organizational
      support.

PMID- 14967182
TI  - Implications of nursing care in the occurrence and consequences of unplanned
      extubation in adult intensive care units.
AB  - This 18-month study used a structured questionnaire to explore the roles of
      nursing care on the occurrence and consequences of unplanned endotracheal
      extubation (UEE) in intensive care units in Taiwan. Experiencing UEE were
      225/1176 (22.5%) intubated patients: 91.7% were self-extubations and 8.3% were
      accidental. Self-extubations occurred most frequently during night shifts and in
      the care of nurses with less working experience. Accidental extubations occurred
      most frequently in patients undergoing routine nursing procedures, usually
      required immediate re-intubation and were associated with more complications. An
      appropriate nurse-to-patient ratio, better working procedures and continual
      nursing education programs might help reduce occurrence and complications of UEE.

PMID- 14967183
TI  - Nursing care of patients with severe acute respiratory syndrome in the intensive
      care unit: case reports in Hong Kong.
AB  - Severe acute respiratory syndrome (SARS) was diagnosed in more than 8437 patients
      in 25 countries between February and July 2003. During this period the World
      Health Organisation issued a global alert about SARS and together with the Centre
      for Disease Control have coordinated their efforts to investigate its
      pathogenesis and treatment. The outbreak in Hong Kong has been dramatic due to
      its geographical proximity with Guangdong province, China where the first case of
      SARS was reported. SARS has been described as a rapidly progressive, sometimes
      fatal pneumonia with a case fatality rate of 7.6% requiring intensive care. The
      four case reports illustrate a number of important points concerning the
      recognition, treatment, management and prevention of SARS, and highlights the
      importance of considering vigilant assessment and monitoring of patients with
      SARS. The purpose of this paper is to share our experiences in caring for
      critically ill patients with SARS in the intensive care unit to nurses globally
      in order to reduce SARS' morbidity and mortality as well as to protect nurses and
      other healthcare workers from this disease that is so far threatening the
      community at large.

PMID- 14967184
TI  - Protection behaviour: a phenomenon affecting organ and tissue donation in the
      21st century?
AB  - UK statistics show that whilst waiting lists for transplantation surgery continue
      to increase, donor numbers are static. This paper describes the hermeneutic phase
      of a mixed method study and puts forward the concept of protection behaviour as
      one explanation for nurses' reticence to discuss post-mortem donation wishes with
      patients' relatives. The desire to protect appears to influence attitudes,
      confidence levels and perceived ability to become involved in donor
      identification and donation discussion, consequently affecting the availability
      of transplantable organs and tissue. By understanding more fully why protective
      behaviours are employed, it increases the likelihood of a solution being found.

PMID- 14967185
TI  - Be good, sweet maid, and let who can be clever: a counter reformation in English
      nursing education?
AB  - The bulk of nursing education in England moved gradually into higher education in
      the 1990s. There were debates over the wisdom of this move and in late 1998 and
      early 1999, it seemed that nursing education might return to the NHS. There was
      considerable discussion in both the nursing and the general press. In this paper
      I concentrate on the latter, and analyse the media discussion of nursing at that
      time, in particular its emphasis on bodily care and excretion, and relate this
      discussion to the literature on the management of pollution in nursing, the
      gendered nature of caring, and the division of labour in nursing.

PMID- 14967186
TI  - Increased unintended patient harm in nursing practise as a consequence of the
      dominance of economic discourses.
AB  - Caring is characterized by close and fragile relations between nurses and
      patients. At times, even with good intentions, nurses cause unintended harm of
      patients. We argue that the dominance of economic discourses in health care and
      their subsequent influence on service delivery and health care practices has the
      potential to increase unintended patient harm. Similar techniques and practices
      can result in either desired outcomes or harmful outcomes. We explore the notion
      of unintended harm and some of the ways it arises in nursing practice. We argue
      there is a clear link between the dominance of economic discourses and an
      increased risk of unintended harm. As a consequence of the dominance of economic
      rationalist discourses and the subsequent systems of control introduced, the
      practice of nursing has been significantly influenced. The challenge for nurses
      and the nursing profession is to develop strategies to refuse to give in to the
      dominance of economic interests over the need to prevent harm.

PMID- 14967187
TI  - Korean health professionals' attitudes and knowledge toward organ donation and
      transplantation.
AB  - The purpose of this study was to identify and analyse Korean health
      professionals' attitudes and knowledge of organ donation and transplantation. An
      exploratory study using semi-structured interviews with nine key informants from
      three major hospitals which provide transplant services in Seoul was conducted.
      Overall, there was a lack of knowledge by Korean health professionals surrounding
      brain death and the organ procurement process. It was also found that the
      participants' attitudes were mixed and somewhat negative, as they did not regard
      brain death as true death. In addition, a majority demonstrated a contradiction
      when it became a more personal issue.

PMID- 14967189
TI  - The effectiveness of nicotine-patch therapy for smoking cessation in patients
      with schizophrenia.
AB  - The purpose of this study was to determine the effectiveness of nicotine-patch
      therapy for smoking cessation in patients with schizophrenia. This was a
      longitudinal study and sixty-eight schizophrenic patients were assigned to 8
      weeks of a nicotine-patch therapy program or a control group. The generalized
      estimating equation analysis revealed that there were significant reductions in
      the subjects' nicotine dependence (Fagerstrom Tolerance Questionnaire), the
      number of cigarettes per day, and CO levels over an 8-week period of nicotine
      patch therapy and 3-month follow-up. The point-prevalence rates of abstinence
      from smoking were an abstinence of 26.9% at 8 weeks and 26.9% at a 3-month follow
      up. At the 3-month follow-up, the rate of continuous smoking abstinence in the
      nicotine-patch group was 23.1%.

PMID- 14967188
TI  - Quality of life of Chinese patients newly diagnosed with gastrointestinal cancer:
      a longitudinal study.
AB  - Cancer of the gastrointestinal (GIT) tract is a major health problem in China.
      The aims of the study were to investigate quality of life of Chinese patients
      newly diagnosed with gastrointestinal (GIT) cancer, identify factors predicting
      quality of life, and to examine the pattern of stability and change in symptoms,
      psychosocial measures and quality of life over a 6 months period. A convenience
      sample of 146 newly diagnosed GIT cancer patients recruited from three major
      hospitals in Shanghai completed a self-report questionnaire initially and 6
      months later. Results indicated that Chinese patients newly diagnosed with GIT
      cancer experience a range of symptoms associated with cancer and its treatment
      that resulted in varying degrees of symptom distress, anxiety and depression, and
      decreased quality of life. Findings from this research give insights into the
      importance of ongoing quality of life assessment, symptom management, and
      intervention to improve quality of life of Chinese cancer patients. It also
      raised questions about measures of quality of life that are culturally relevant.

PMID- 14967190
TI  - Examining the validity of pressure ulcer risk assessment scales: a replication
      study.
AB  - Risk assessment scales (RASs) intended to identify patients most at risk of
      developing pressure ulcers have been widely used for many years. Numerous studies
      have evaluated their predictive validity but potential bias has been inherent in
      the design of all. To overcome these problems a simulation study was conducted in
      which clinical nurses were asked to identify the degree of risk experienced by
      four patients employing the three RASs discussed most frequently in the
      literature (Norton, Braden and Waterlow Scores). These findings were compared
      with nurses' clinical judgment rated on a visual analogue scale. The simulations
      consisted of high-resolution photographs accompanied by case studies of the
      patients. The nurses' scores were compared to estimates of risk generated by an
      expert panel. Nurses' clinical judgment agreed much more closely with expert
      opinion than any of the RASs. A replication study was undertaken to confirm these
      findings. One hundred and fifteen nurses participated in replication. Again the
      nurses' clinical judgment matched expert opinion much more closely than the
      results of the RASs. Replication also drew attention to a number of
      methodological issues which deserve consideration when using simulation to test
      the effectiveness of clinical tools and the need to establish adequate measures
      of external validity whenever use of this method is contemplated.

PMID- 14967191
TI  - Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline
      drugs.
AB  - Two subclasses of quinoline antimalarial drugs are used clinically. Both act on
      the endolysosomal system of malaria parasites, but in different ways. Treatment
      with 4-aminoquinoline drugs, such as chloroquine, causes morphologic changes and
      hemoglobin accumulation in endocytic vesicles. Treatment with quinoline-4
      methanol drugs, such as quinine and mefloquine, also causes morphologic changes,
      but does not cause hemoglobin accumulation. In addition, chloroquine causes
      undimerized ferriprotoporphyrin IX (ferric heme) to accumulate whereas quinine
      and mefloquine do not. On the contrary, treatment with quinine or mefloquine
      prevents and reverses chloroquine-induced accumulation of hemoglobin and
      undimerized ferriprotoporphyrin IX. This difference is of particular interest
      since there is convincing evidence that undimerized ferriprotoporphyrin IX in
      malaria parasites would interact with and serve as a target for chloroquine.
      According to the ferriprotoporphyrin IX interaction hypothesis, chloroquine would
      bind to undimerized ferriprotoporphyrin IX, delay its detoxification, cause it to
      accumulate, and allow it to exert its intrinsic biological toxicities. The
      ferriprotoporphyrin IX interaction hypothesis appears to explain the antimalarial
      action of chloroquine, but a drug target in addition to ferriprotoporphyrin IX is
      suggested by the antimalarial actions of quinine and mefloquine. This article
      summarizes current knowledge of the role of ferriprotoporphyrin IX in the
      antimalarial actions of quinoline drugs and evaluates the currently available
      evidence in support of phospholipids as a second target for quinine, mefloquine
      and, possibly, the chloroquine-ferriprotoporphyrin IX complex.

PMID- 14967192
TI  - Influence of surgical pain stress on the blood-brain barrier permeability in
      rats.
AB  - Effect of surgical pain stress on the blood-brain barrier permeability was
      investigated in rats. The animals were divided into four groups: Group 1:
      control, Group 2: immobilization stress, Group 3: acute hypertension, Group 4:
      immobilization stress + surgical pain stress. Bilateral hid paw surgical wounds
      for cannulations were applied in animals' inguinal regions under diethyl-ether
      anesthesia, then the animals were awaken from anesthesia to produce surgical pain
      stress. Evans-blue was used as a blood-brain barrier tracer. There is no
      significantly blood-brain barrier breakdown after short-time immobilization
      stress, but after adrenalin hypertension blood-brain barrier permeability was
      increased especially on frontal and occipital cortices in 50% of the animals.
      Surgical pain stress increased blood-brain barrier permeabiliy in comparison to
      acute adrenalin-induced hypertension (p < 0.01). In surgical pain stress-induced
      animals distinct Evans-blue leakage was observed in the occipital, frontal and
      parieto-temporal cortices.

PMID- 14967193
TI  - Hsp90 inhibitors attenuate effect of dexamethasone on activated NF-kappaB and AP
      1.
AB  - Heat shock protein 90 (Hsp90) regulates the functions of glucocorticoid receptor
      (GR). Hsp90 inhibitors geldanamycin (GA) and radicicol (Rad) have been studied as
      anti-inflammatory agents; however, their effects on glucocorticoid-mediated anti
      inflammatory mechanism are not known. In the present study, we examined the
      effects of dexamethasone (Dex) and Hsp90 inhibitors, alone and in combination, on
      the activation of GR and proinflammatory transcription factors such as nuclear
      factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). In cell-based reporter
      assay, Hsp90 inhibitors inhibited Dex-induced nuclear import and transcriptional
      activity of GR. Both tumor necrosis factor-alpha-activated NF-kappaB and phorbol
      ester-activated AP-1 were inhibited by Dex and Hsp90 inhibitors alone. When the
      cells were treated with a combination of these drugs, the inhibitory effect of
      Dex was significantly attenuated by Hsp90 inhibitors. We further examined the
      effects of Dex and Rad on lipopolysaccharide-induced gene expressions of the
      proinflammatory cytokine interleukin (IL)-1beta in macrophages. Dex, but not Rad,
      inhibited IL-1beta expression. Rad concentration-dependently attenuated the
      inhibitory effect of Dex. These results suggest that Hsp90 inhibitor itself
      inhibits the activation of NF-kappaB and AP-1, however, impedes Dex-induced
      inhibition of IL-1beta induction by attenuating Dex-mediated activation of GR and
      inhibition of the proinflammatory transcription factors.

PMID- 14967194
TI  - Single neonatal treatment with beta-endorphin (hormonal imprinting) extremely
      enhances nocistatin level of cerebrospinal fluid in adult rats.
AB  - In earlier experiments endorphin treatment of newborn rats caused the decrease of
      brain serotonin content, increasing aggressivity, enhanced sexual activity of
      females and changes in the binding capacity of uterine estrogen receptors at
      adult age, however nociceptin content of the cerebrospinal fluid was not changed.
      In the present experiment neonatal treatment of male and female rats was done
      with a single dose of 3 microg beta-endorphin and in five months old rats the
      level of nociceptin antagonist nocistatin was determined by radioimmunoassay in
      the cerebrospinal fluid. In both genders the amount of nocistatin was one
      magnitude higher in the endorphin treated groups. There was also a significant
      difference between the male and female nocistatin level in the treated and non
      treated groups alike, with the advantage of females. The results call attention
      to the possibility of influencing pain-tolerance for life, by the pain-provoked
      endorphin levels during delivery.

PMID- 14967195
TI  - The effects of atypical antipsychotics on visceral fat distribution in first
      episode, drug-naive patients with schizophrenia.
AB  - The aim of this study was to determine the location of antipsychotic-induced
      weight gain in drug naive, first episode patients with schizophrenia. Various
      fatness and fat distribution parameters (by Computerized Tomography scanning and
      anthropometry) and 1600 hr plasma cortisol were measured in 19 (15 men and 4
      women) subjects with schizophrenia (mean age = 31.0 years; mean body mass index
      [BMI] = 24.6 kg/m2) and an equal number of age- and sex- matched controls (mean
      age = 32.6 yr; mean BMI = 23.0 kg/m2). Patients were then given either olanzapine
      or risperidone. Sixteen patients were re-tested following a treatment period
      lasting approximately 6 months. Patients with schizophrenia, had significantly
      more intra-abdominal fat [IAF] (116.8 +/- 20.2 cm2 vs. 38.0 +/- 4.8 cm2,
      respectively; t = 3.80, df = 18, p < 0.0001) and had higher levels of plasma
      cortisol (360.2 +/- 49.6 nmol/L vs. 192.7 +/- 19.7 nmol/L, respectively; t =
      3.13, df = 18, p < 0.003) than appropriately matched control subjects. Treatment
      with atypical antipsychotics did not result in a significant increase in IAF
      (116.8 +/- 20.2 cm2 vs. 131.7 +/- 20.9 cm2; p = NS) though visceral fat stores
      still remained significantly higher than those seen in controls (38.0 +/- 4.8
      cm2) (F = 9.34; df = 2, 51; p < 0.0003). However, plasma levels of cortisol did
      significantly decrease (360.2 +/- 49.6 nmol/L +/- vs. 316.2 +/- 48.4 nmol/L; p <
      0.05). Pre-treatment levels of IAF did not differ between those who received
      risperidone and those who were given olanzapine (123.0 +/- 35.9 cm2 vs. 113.1 +/-
      15.7 cm2, respectively; t = 0.20, df = 16, p < 0.84). The increase in IAF did not
      differ between those given risperidone and those who received olanzapine (26.9 +/
      12.1 cm2 vs. 18.24 +/- 11.44 cm2, respectively; t = 0.50, df = 16, p < 0.63).
      Patients with drug naive, first episode, schizophrenia have higher levels of
      visceral fats stores as compared to matched control subjects. Treatment with
      atypical antipsychotics does not result in a significant increase in IAF
      distribution.

PMID- 14967196
TI  - Motor behavior and brain enzymatic changes after acute lead intoxication on
      different strains of mice.
AB  - Lead is a nonphysiological metal that has been implicated in toxic processes that
      affect several organ systems in humans and other animals. Although the brain
      generally has stronger protective mechanisms against toxic substances than other
      organs have, exposure to lead results in several neurophysiological and
      behavioral symptoms. The administration of a single injection (i.p.) of lead
      acetate in mice is a model of acute Pb2 + toxicity. In the present study, this
      model was used to explore the magnitude of the effect of different doses, time
      intervals and mice strains on several biobehavioral parameters. We investigated
      the effects of acute lead acetate administration on body and brain weight, brain
      lead acetate accumulation and specially, spontaneous locomotion and brain
      catalase activity. Lead acetate was injected i.p. in outbred (Swiss or CD1) and
      inbred (BALB/c, C57BL/J6 or DBA/2) mice at doses of 0, 50, 100, 150 or 200 mg/kg.
      At different time intervals following this acute treatment, several biochemical,
      physiological and behavioral responses were recorded. Results indicated that
      acute lead acetate has deleterious dose-dependent effects on brain and body
      weight. The effect on body weight in the present study was transient, although
      lead acetate was detected in neural tissues for several days after
      administration. Spontaneous locomotor activity only was reduced up until 24
      hours. The effect of lead on body weight was strain-dependent, with Swiss mice
      showing greater resistance compared to the other strains. Total brain catalase
      activity in lead-pretreated Swiss mice showed a significant induction. This
      enzymatic upregulation could provide a protective mechanism for oxidative stress
      in these mice.

PMID- 14967197
TI  - Role of histamine and acid back-diffusion in modulation of gastric microvascular
      permeability and hemorrhagic ulcers in Salmonella typhimurium-infected rats.
AB  - Documentation concerning the pathogenesis of gastric hemorrhagic ulcer in
      Salmonella typhimurium (Salmonella typhi)-infective disease is lacking. This
      research first proposed that alterations of mast cell histamine release, gastric
      acid back-diffusion and mucosal microvascular permeability are important in
      modulating gastric ulcer and hemorrhage in Salmonella typhi-infected rats.
      Additionally, effects of several histamine-related drugs on this ulcer model were
      evaluated. Male Wistar rats were deprived food for 36 h. Live cultures of
      Salmonella typhi (OU 5045, 1 x 10(10) CFU in 1.0 mL of sterilized phosphate
      buffer saline) were challenged, intrajejunally to rats just before withdrawal of
      food. Control rats received the same volume of sterilized vehicle only. Rat
      stomachs were irrigated for 3 h with either normal saline or simulated gastric
      juice. Gastric acid back-diffusion, mucosal histamine concentration,
      microvascular permeability as well as luminal hemoglobin content and ulcer areas
      were determined. Severe gastric hemorrhage and mucosal ulcerations, particularly
      in acidic stomachs, were observed in Salmonella typhi-infected rats. A positive
      correlation of histamine to gastric hemorrhage and ulcer was found in those rats
      with Salmonella typhi-infection. This hemorrhagic ulcer in Salmonella typhi
      infected rats was effectively ameliorated by intraperitoneal ketotifen,
      diphenhydramine and ranitidine but was worsen by exogenous histamine or diamine
      oxidase. In conclusion, enhancement of acid back-diffusion, mast cell histamine
      release and microvascular permeability is important in modulating gastric
      hemorrhage and ulcer in Salmonella typhi-infected rats.

PMID- 14967198
TI  - Inhibitory effects on phospholipase A2 and antivenin activity of melanin
      extracted from Thea sinensis Linn.
AB  - Antivenin activity of melanin extracted from black tea (MEBT) was reported for
      the first time. The antagonistic effect of MEBT was evaluated for Agkistrodon
      contortrix laticinctus (broadbanded copperhead), Agkistrodon halys blomhoffii
      (Japanese mamushi), and Crotalus atrox (western diamondback rattlesnake) snake
      venoms administered i.p. to ICR mice. MEBT was injected i.p. immediately after
      the venom administration in dose of 3 mg per mouse in the same place of venom
      injection. MEBT demonstrated neutralization effect against all venoms tested. The
      greatest antivenin effect of MEBT was found against Japanese mamushi snake venom.
      In this case, half the mice died within 2.5 +/- 0.7 h after injection of 0.9
      mg/kg of venom. An immediate injection of MEBT substantially reduced the toxic
      effect of venom and extended time at the 50% level of survival up to 52.3 +/- 2.3
      h. The antivenin activity of MEBT is due to chelating of Ca++ and non-specific
      binding of phospholipase A2. The inhibitory effect of MEBT on phospholipase A2
      assessed for different venoms was similar to that obtained with pure enzyme. Low
      toxicity of MEBT in combination with its antagonistic activity against different
      venoms may allow effective life-saving treatment against snakebites. Such
      application of MEBT is important when identification of the snake is impossible
      or if specific treatment is unavailable.

PMID- 14967199
TI  - Estrogen modulates the action of nitric oxide in the medial preoptic area on
      luteinizing hormone and prolactin secretion.
AB  - Several substances work as neuromediators of the estrogen direct and indirect
      (through glial cells or interneurons) action on luteinizing hormone- releasing
      hormone (LH-RH) neurons in medial basal hypothalamus and medial preoptic area
      (MPOA). Angiotensin II (AII) in the MPOA stimulates the LH and it inhibits PRL
      secretion in some situations. On the other hand, the effect of excitatory amino
      acids on LH and PRL surges during proestrus as well LH surge induced by steroids
      depend on nitric oxide (NO). In the present study we investigated the
      participation of MPOA endogenous NO on gonadotropin and PRL secretion mediated by
      estrogen and AII. Plasma LH, FSH and PRL was determinated in estrogen primed and
      unprimed ovariectomized Wistar rats that received microinjection of AII or saline
      into the MPOA, associated or not with a previous microinjection of an inhibitor
      for NOS. Our results show the following: 1 - there was no change in plasma FSH in
      estrogen- primed or unprimed ovarictomized related with microinjections of AII or
      NO antagonist in the MPOA; 2- the increase in LH secretion after ovariectomy
      depends on, at least in part, NO activity in the MPOA; 3- estrogen may have an
      indirect negative feedback action on LH-RH neurons in the MPOA through NO; 4- the
      stimulatory action of AII in the MPOA on LH secretion in ovariectomized rats
      treated with estrogen depends on NO; 5 - NO in the MPOA stimulates or inhibits
      PRL secretion depending on the absence or presence of estrogen, respectively; 6-
      the inhibitory action of AII into the MPOA on PRL secretion does not seem to
      depend on NO.

PMID- 14967200
TI  - Antihepatoma activity of Physalis angulata and P. peruviana extracts and their
      effects on apoptosis in human Hep G2 cells.
AB  - Physalis angulata and P. peruviana are herbs widely used in folk medicine. In
      this study, the aqueous and ethanol extracts prepared from the whole plant of
      these species were evaluated for their antihepatoma activity. Using XTT assay,
      three human hepatoma cells, namely Hep G2, Hep 3B and PLC/PRF/5 were tested. The
      results showed that ethanol extract of P. peruviana (EEPP) possessed the lowest
      IC50 value against the Hep G2 cells. Interestingly, all extracts showed no
      cytotoxic effect on normal mouse liver cells. Treatment with carbonyl cyanide m
      chlorophenyl hydrazone, a protonophore, caused a reduction of membrane potential
      (Deltapsim) by mitochondrial membrane depolarization. At high concentrations,
      EEPP was shown to induce cell cycle arrest and apoptosis through mitochondrial
      dysfunction as demonstrated by the following observations: (i) EEPP induced the
      collapse of Deltapsim and the depletion of glutathione content in a dose
      dependent manner; (ii) pretreatment with the antioxidant (1.0 microg/ml vitamin
      E) protected cells from EEPP-induced release of ROS; and (iii) at concentrations
      10 to 50 microg/ml, EEPP displayed a dose-dependent accumulation of the Sub-G1
      peak (hypoploid) and caused G0/G1-phase arrest. Apoptosis was elicited when the
      cells were treated with 50 microg/ml EEPP as characterized by the appearance of
      phosphatidylserine on the outer surface of the plasma membrane. The results
      conclude that EEPP possesses potent antihepatoma activity and its effect on
      apoptosis is associated with mitochondrial dysfunction.

PMID- 14967201
TI  - Mercury-induced Ca2+ increase and cytotoxicity in renal tubular cells.
AB  - The effect of mercury (Hg2+), a known nephrotoxicant, on intracellular free Ca2+
      levels ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells was explored. [Ca2+]i
      was measured by using the Ca2+ -sensitive dye fura-2. Hg2+ increased [Ca2+]i in a
      concentration-dependent manner with an EC50 of 6 microM. The Ca2+ signal
      comprised a gradual increase. Removal of extracellular Ca2+ decreased the Hg2+ 
      induced [Ca2+]i increase by 27%, suggesting that the Ca2+ signal was due to both
      extracellular Ca2+ influx and store Ca2+ release. In Ca2+ -free medium, the Hg2+ 
      induced [Ca2+]i increase was nearly abolished by pretreatment with 1 microM
      thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), and conversely,
      pretreatment with Hg2+ abolished thapsigargin-induced Ca2+ increase. Hg2+ 
      induced Ca2+ release was not altered by inhibition of phospholipase C but was
      potentiated by activation of protein kinase C. Overnight treatment with 1 microM
      Hg2+ did not alter cell proliferation rate and mitochondrial activity, but 10
      microM Hg2+ killed all cells. Collectively, this study shows that Hg2+ induced
      protein kinase C-regulated [Ca2+]i increases in renal tubular cells via releasing
      store Ca2+ from the endoplasmic reticulum in a manner independent of
      phospholipase C activity. Hg2+ also caused cytotoxicity at higher concentrations.

PMID- 14967202
TI  - Correlations between fixation stability and visual motion sensitivity.
AB  - To assess influences of fixational drift eye movements on motion detection, lower
      thresholds for motion and drift amplitudes were measured in normal subjects. The
      threshold was higher without visible surrounds than with a surround, and had a
      positive correlation with drift amplitude. The same effect, but more pronounced,
      was found when the surround was visible but flickered synchronously. In contrast,
      the correlation disappeared in the threshold with a static surround. These
      results suggest that, while spurious image motions by eye drift can have a
      detrimental effect, a mechanism tuned for differential motions normally
      counteracts it.

PMID- 14967203
TI  - Event-related potential correlates of judgment categories and detection
      sensitivity in a visual detection task.
AB  - Event-related potentials were recorded from human subjects performing a visual
      detection task to find correlates of detection performance (d' and beta) in
      accordance with the theory of signal detection. Two spatial frequencies of square
      waves shifted horizontally with three shifting-step varieties were presented to
      the subjects who reported whether or not the waves were perceived to shift.
      Although three components of N1, P2, and P3 were observed for all of four
      response categories of hit, miss, false alarm, and correct rejection, only the
      amplitudes of the P3 component at vertex and parietal sites highly correlated to
      the detection sensitivity of d'. It was also found that coefficients of
      correlation between the P3 amplitudes at these sites and observed hit and false
      alarm rates were highly significant and a d'-extrapolation value reproduced by
      the normalized P3 amplitudes and the usual d' indicated a highly linear trend.
      Results suggest that generation of the P3 component is associated with "threshold
      modulating" mechanisms which determine detection sensitivity of a task for each
      perceptual event.

PMID- 14967204
TI  - Higher-contrast is preferred to equal-contrast in stereo-matching.
AB  - Stereoscopic vision is achieved by matching images in the two eyes. It is well
      known that the match is easily established even when the two images significantly
      differ in their contrast. It is shown in this study that, given the choice
      between a global match to a monocular image of the same contrast or a global
      match to an image of a higher-contrast, the higher-contrast match is preferred.
      This counter-intuitive result undermines correlation measures used in various
      stereo-matching algorithms, which minimize the difference between matched images.
      Instead, this preference can be described by a correlation measure maximizing a
      scalar product between matched images defined in multi-dimensional feature space.
      It is shown how such a correlation measure can be easily calculated based on cell
      types abundant in primary visual cortex.

PMID- 14967205
TI  - Apparent 3-D image perceived from luminance-modulated two 2-D images displayed at
      different depths.
AB  - An apparent 3-D image can be perceived from only two 2-D images displayed at
      different depths, when an observer views them from the direction in which they
      are overlapped. The two 2-D images are created from an original 2-D image by
      dividing its luminance according to independently obtained depth information.
      Subjective test results show that (1) an apparent 3-D image is perceived and (2)
      the perceived depth continuously varies according to the change in luminance
      ratio between the two 2-D images.

PMID- 14967206
TI  - Psychophysical receptive fields of edge detection mechanisms.
AB  - Theories of edge detection generally assume a front-end linear stage involving
      some population of neural filters. Here we study these early mechanisms using
      psychophysical techniques, and evaluate a number of models for edge detection. We
      measured psychophysical efficiency for detection of noisy luminance edge stimuli
      over a range of stimulus sizes and shapes. The data suggest a diversity in
      receptive field shape and orientation bandwidth, consistent with physiological
      evidence, but inconsistent with standard multi-channel models of visual
      processing.

PMID- 14967207
TI  - Interpolating sampled contours in 3D: perturbation analyses.
AB  - In four experiments, observers interpolated parabolic sampled contours confined
      to planes in three-dimensional space. Each sampled contour consisted of eight
      visible points, placed irregularly along the otherwise invisible parabolic
      contour. Observers adjusted an additional point until it fell on the contour. We
      sought to determine how each visible point influenced interpolation by measuring
      the effect of slightly perturbing its location. Influence fell rapidly to zero as
      distance from the interpolated point increased, indicating that human visual
      interpolation of parabolic contours is local. We compare the measured influence
      for human observers to that predicted by three standard interpolation algorithms.
      The results were inconsistent with a fit of a quadratic to the points, but were
      reasonably consistent with a cubic spline and most consistent with an algorithm
      that minimizes the variance of angles between neighboring line segments defined
      by the sampled points.

PMID- 14967208
TI  - Diffuse luminance flicker increases blood flow in major retinal arteries and
      veins.
AB  - It has been shown that diffuse luminance flicker increases optic nerve head blood
      flow. The current study has been performed to quantify changes in retinal blood
      flow during flicker stimulation. In a group of 11 healthy volunteers, red blood
      cell velocity and retinal vessel diameters were assessed with bi-directional
      laser Doppler velocimetry and the Zeiss retinal vessel analyzer before, during
      and after stimulation with diffuse luminance flicker. Retinal blood flow was
      calculated for each condition. Flicker stimulation increased retinal blood flow
      by +59 +/- 20% (p<0.01) in arteries and by +53 +/- 25% (p<0.01) in retinal veins.
      These results demonstrate that diffuse luminance flicker increases retinal blood
      flow in the human retina.

PMID- 14967209
TI  - Reducing noise in suspected glaucomatous visual fields by using a new spatial
      filter.
AB  - Visual field testing with automated perimetry is hampered by the amount of noise
      present in the readings. Here, we derive a physiologically accurate spatial
      filter to be applied to the data after patient examination. The filter was tested
      by a Virtual Eye computer simulation. By simulating series of stable fields it
      was shown that specificity of determining visual field changes was improved;
      while simulating progressing fields (based on a map of the optic nerve head) it
      was shown that sensitivity was also improved. The filter appears to reduce the
      noise in glaucomatous visual field data and may be clinically useful.

PMID- 14967210
TI  - The importance of interhemispheric transfer for foveal vision: a factor that has
      been overlooked in theories of visual word recognition and object perception.
AB  - In this special issue of Brain and Language, we examine what implications the
      division between the left and the right brain half has for the recognition of
      words presented in the center of the visual field. The different articles are a
      first indication that taking into account the split between the left and the
      right cerebral hemisphere need not be an inescapable nuisance in models of visual
      word recognition but may in fact form the clue to the solution of a longstanding
      problem within this literature. Also, the fact that interhemispheric transfer has
      implications for foveal word recognition should interest laterality researchers,
      as it makes their findings more central to normal reading. In this introductory
      article, I first present a rough picture of the current (lack of) evidence for a
      bilateral representation of the fovea and the absence of a callosal delay. I then
      briefly discuss the suggestions made by the different authors on how to integrate
      the foveal split within current models of visual word recognition.

PMID- 14967211
TI  - A historical review of the representation of the visual field in primary visual
      cortex with special reference to the neural mechanisms underlying macular
      sparing.
AB  - This article comprises a historical review of the literature pertaining to the
      representation of the visual field in human primary visual cortex. A brief survey
      of the anatomy of the visual system is followed by a critical evaluation of the
      key studies that have informed both the issue of the disproportionate
      representation of central vision within primary visual cortex, and the anatomical
      basis underlying the phenomena of macular sparing and macular splitting
      hemianopia.

PMID- 14967212
TI  - Hemisphere-specific effects in word recognition do not require hemisphere
      specific modes of access.
AB  - Consistent with converging experimental evidence, we assume that foveal
      information is initially split across the two cerebral hemispheres. We have
      previously presented the SERIOL model of letter-position coding, which specifies
      how the resulting two halves of a letter string are integrated into an abstract
      representation of letter order. This representation is based on ordered pairs of
      two letters (bigrams); such a representation is created for input occurring at
      any location in the visual field. Various studies have shown hemisphere-specific
      effects in lexical access by using unilateral presentation of stimuli. While the
      hemisphere-independent means of lexical access in the SERIOL model (via bigrams)
      may seem inconsistent with these findings, we propose that such effects arise
      from the hemisphere-specific transformations necessary to create the bigram
      representation. We provide a theoretical account of the finding that high N
      (lexical neighborhood size) evokes facilitation in the RH, but not the LH
      (Lavidor & Ellis, 2002a, 2002b); an experiment discussed elsewhere (Whitney &
      Lavidor, 2003) has verified key predictions of this account. We also discuss the
      differing effects of word length across visual fields.

PMID- 14967213
TI  - Reading habits, perceptual learning, and recognition of printed words.
AB  - The present work aims at demonstrating that visual training associated with the
      act of reading modifies the way we perceive printed words. As reading does not
      train all parts of the retina in the same way but favors regions on the side in
      the direction of scanning, visual word recognition should be better at retinal
      locations that are frequently used during reading. In two studies that probed
      word and letter discriminations we provided evidence for a correlation between
      eye fixation pattern during reading and performance. We showed that effects of
      reading-related visual training were stimulus-specific in the sense that it
      affected the perception of words but not that of visually unfamiliar non-words.
      This stimulus specificity was also evident in the legibility of individual
      characters of the Roman and the Hebrew scripts-two scripts that are read in
      opposing directions. When displayed within a sequence of homogenous letters
      (e.g., xxexx) the legibility of a target character varied with the location of
      the sequence in the visual field and with the serial position of the target
      within the sequence. This retinal location- and context-dependency differed
      between Roman and Hebrew characters. These results seem to indicate that reading
      modifies the functional structure of early stages in the visual pathway. The
      cortical network that supports reading seems to comprise components of the visual
      cortex of both hemispheres before it lateralizes to the left hemisphere.
      Expanding the reading network to include these visual regions will shed a
      different light on the potential role of the visual word form area (e.g., ) in
      word recognition and on the organization of the reading system in general.

PMID- 14967214
TI  - Evaluating a split processing model of visual word recognition: effects of
      orthographic neighborhood size.
AB  - The split fovea theory proposes that visual word recognition of centrally
      presented words is mediated by the splitting of the foveal image, with letters to
      the left of fixation being projected to the right hemisphere (RH) and letters to
      the right of fixation being projected to the left hemisphere (LH). Two lexical
      decision experiments aimed to elucidate word recognition processes under the
      split fovea theory are described. The first experiment showed that when words
      were presented centrally, such that the initial letters were in the left visual
      field (LVF/RH), there were effects of orthographic neighborhood, i.e., there were
      faster responses to words with high rather than low orthographic neighborhoods
      for the initial letters ('lead neighbors'). This effect was limited to lead
      neighbors but not end-neighbors (orthographic neighbors sharing the same final
      letters). When the same words were fully presented in the LVF/RH or right visual
      field (RVF/LH, Experiment 2), there was no effect of orthographic neighborhood
      size. We argue that the lack of an effect in Experiment 2 was due to exposure to
      all of the letters of the words, the words being matched for overall orthographic
      neighborhood count and the sub-parts no longer having a unique effect. We
      concluded that the orthographic activation found in Experiment 1 occurred because
      the initial letters of centrally presented words were projected to the RH. The
      results support the split fovea theory, where the RH has primacy in representing
      lead neighbors of a written word.

PMID- 14967215
TI  - Orthographic contributions to perceived word center.
AB  - We have a surprising tendency to misperceive the center of visually presented
      words (). To understand the origin of this bias, four experiments assessed the
      impact of letter font, letter size, and grapheme-phoneme convergences on
      perceived stimulus center. Fourteen observers indicated the perceived centers of
      words, pseudowords, consonant strings, and lines with a mouse cursor. Visual
      orthographic factors had no effect on perceived word center but grapheme-phoneme
      convergence did: Observers compensated for strong grapheme-phoneme asymmetries in
      the letter strings. These findings support the idea that the cognitive
      representation of words is spatially distorted as a result of lexical access
      mechanisms.

PMID- 14967216
TI  - Magnetic stimulation studies of foveal representation.
AB  - The right and left visual fields each project to the contralateral cerebral
      hemispheres, but the extent of the functional overlap of the two hemifields along
      the vertical meridian is still under debate. After presenting the spatial,
      temporal, and functional specifications of Transcranial Magnetic Stimulation
      (TMS), we show that TMS is particularly suitable to study the question of foveal
      representation as it allows one to study the effects of selective disruption of
      left or right hemisphere functions on the processing of centrally presented
      stimuli. Future strategies for the use of TMS in further tests of visual word
      recognition are suggested.

PMID- 14967217
TI  - Hemispheric asymmetries in the split-fovea model of semantic processing.
AB  - We report a series of neural network models of semantic processing of single
      English words in the left and the right hemispheres of the brain. We implement
      the foveal splitting of the visual field and assess the influence of this
      splitting on a mapping from orthography to semantic representations in single
      word reading. The models were trained on English four-letter words, presented
      according to their frequency in all positions encountered during normal reading.
      The architecture of the model interacted with the training set to produce
      processing asymmetries comparable to those found in behavioral studies. First,
      the cueing effects of dominant and subordinate meanings of ambiguous words were
      different for words presented to the left or to the right of the input layer.
      Second, priming effects of groups of related words were stronger in the left
      input than the right input of the model. These effects were caused by coarser
      coding in the right half compared with the left half of the model, an emergent
      effect of the split model interacting with informational asymmetries in the left
      and right parts of words in the lexicon of English. Some or all of the behavioral
      data for reading single words in English may have a similar origin.

PMID- 14967218
TI  - Length, formats, neighbours, hemispheres, and the processing of words presented
      laterally or at fixation.
AB  - It has long been known that the number of letters in a word has more of an effect
      on recognition speed and accuracy in the left visual field (LVF) than in the
      right visual field (RVF) provided that the word is presented in a standard,
      horizontal format. After considering the basis of the length by visual field
      interaction two further differences between the visual fields/hemispheres are
      discussed: (a) the greater impact of format distortion (including case
      alternation) in the RVF than in the LVF and (b) the greater facilitation of
      lexical decision by orthographic neighbourhood size (N) in the LVF than in the
      RVF. In the context of split fovea accounts of word recognition, evidence is
      summarised which indicates that the processing of words presented at fixation is
      affected by the number of letters to the left of fixation but not by the number
      of letters to the right and by the number of orthographic neighbours activated by
      letters to the left of fixation but not by the number of orthographic neighbours
      activated by letters to the right of fixation. A model of word recognition is
      presented which incorporates the notion that the left hemisphere has sole access
      to a mode of word recognition that involves parallel access from letter forms to
      the visual input lexicon, is disrupted by format distortion, and does not employ
      top-down support of the letter level by the word level.

PMID- 14967219
TI  - Interleukin-1 inhibits interleukin-15 production by progesterone during in vitro
      decidualization in human.
AB  - Interleukin (IL)-15 is a novel cytokine that plays important roles in uterine
      natural killer cell function and one of the candidate genes that is upregulated
      during the window of implantation for human endometrium. IL-15 expression and
      production by human endometrial stromal cells (ESCs) is elevated during in vitro
      decidualization by progesterone (P). In the present study, we evaluated the
      effects of IL-1beta, a proinflammatory cytokine, on IL-15 production in ESCs. By
      enzyme-linked immunosorbent assay (ELISA), IL-1beta had no effect on IL-15
      production from ESCs in short-term culture (for 24 h), whereas IL-1beta
      stimulated production of IL-8. However, using ELISA and Northern blot analyses we
      found that IL-1beta significantly inhibited P-induced IL-15 production and mRNA
      expression in long-term culture (for 12 days) of ESCs in vitro (P<0.01). This
      inhibition was not due to IL-1beta-mediated cytotoxicity, as ESCs cultured in the
      presence of IL-1beta showed no evidence of significant change in their viability.
      These results suggest that ovarian steroid hormones and IL-1beta regulate IL-15
      mRNA expression and protein production in long-term culture, and that IL-1beta
      plays a role as a negative regulator of IL-15 production during decidualization
      in human endometrium.

PMID- 14967220
TI  - Pre-eclampsia: associated with increased syncytial apoptosis when the infant is
      small-for-gestational-age.
AB  - The present investigation was undertaken to study the association between
      placental apoptosis and pre-eclampsia, discriminating between pre-eclamptic
      pregnancies with appropriate-, and small-for-gestational-age (SGA), infants.
      Twenty pregnancies with pre-eclampsia and SGA (birth weight at or below -2
      standard deviations) infants were selected in a retrospective study.
      Subsequently, corresponding numbers of gestational age-matched pre-eclampsia
      cases with appropriate-gestational-age (AGA) (birth weight at or above the 50%
      centile) infants and AGA controls without pre-eclampsia were selected. Formalin
      fixed placental tissue was obtained from all groups. Apoptosis was assessed by a
      monoclonal antibody (M30), detecting a neoepitope of cytokeratin that is
      generated early in the apoptotic cascade. M30-positive cells were counted in
      villous and decidual/ basal plate tissue fields, and results were given as
      numbers of M30-positive cells per field. The study was performed blinded.
      Increased apoptosis was found in the syncytiotrophoblast layer in pre-eclampsia
      with SGA infants (0.14 apototic incidents per field of villous tissue, with 0.04
      0.23 as the corresponding 25-75% inter quartile range (IQR) (P=0.05)). Syncytial
      apoptosis in the syncytial layer in the pre-eclampsia group with AGA infants was
      lower (0.09, IQR 0.03-0.15) and corresponded to the level detected among controls
      (0.06, IQR 0.03-0.17). Apoptosis in other placental cellular compartments did not
      differ between groups. The increased syncytial apoptosis found in placentas from
      pregnancies with SGA infants may either be due to specific mechanisms associated
      with pre-eclampsia complicated with growth restriction, or may simply reflect the
      presence of syncytiotrophoblast layer damage, regardless of underlying
      pathological condition.

PMID- 14967221
TI  - PCR-DGGE fingerprinting: novel strategies for detection of microbes in food.
AB  - Polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE)
      fingerprinting was recently introduced into food microbiology. This paper
      describes the technique and reports on the state-of-the-art application of this
      technique to food and food-related ecosystems. Applications of PCR-DGGE in
      several fields of food microbiology are reviewed: the identification of
      microorganisms isolated from food, the evaluation of microbial diversity during
      food fermentation, and microbiological and commercial food quality assessment.
      Potentials and limitations of this culture-independent approach in food
      microbiology are indicated and future perspectives are discussed.

PMID- 14967222
TI  - Comparative evaluation of PCR assays for the robust molecular detection of
      Mycobacterium avium subsp. paratuberculosis.
AB  - Mycobacterium avium subsp. paratuberculosis (MAP) can cause a very serious, often
      fatal disease, namely paratuberculosis, in several animal species, especially
      ruminants. Recently, it has also been implicated in the pathogenesis of
      Infectious Bowel Disease of man. The aim of this study was to develop a molecular
      method for the routine detection and identification of MAP, from tissue samples
      of animal origin. The proposed assay would have to combine optimum performance
      and cost, with high reproducibility. To this goal, three laboratories in Greece
      and the Czech Republic undertook different parts of a study that involved
      evaluation of DNA extraction procedures, and PCR assays, for MAP detection. For
      DNA extraction we used one in-house, and one commercial method, and for the PCR
      we assessed a number of different assays, starting with the evaluation of primer
      specificity with an extended GenBank database search. Based on these results, we
      chose to assess a one-tube nested, 2 two-tube nested, and a single PCR assay,
      targeted to different genomic regions of the IS900 element. These four methods
      were applied on positive and negative control samples, consisted of pure
      bacterial cultures and formalin-fixed paraffin-embedded (FFPE) tissue samples
      collected from cattle with paratuberculosis and chickens with M. avium subsp.
      avium infection. Based on the criteria of reliability and cost, the procedure
      that performed better was the one-tube nested PCR assay combined with the in
      house DNA extraction method. The agreement of the results obtained by the three
      collaborating laboratories indicates the reliability of the proposed assay even
      under different laboratory conditions.

PMID- 14967223
TI  - Development of alternate ssu-rRNA probing strategies for characterizing aquatic
      microbial communities.
AB  - Plastids in phytoplankton retain prokaryote-like DNA sequences that may generate
      false-positive signals from eubacterial small subunit (ssu) rRNA oligonucleotide
      probes, resulting in the overestimation of bacterial activity in aquatic
      microbial communities. To assess the extent of possible plastid-associated
      binding to eubacterial signals, we performed an extensive database search, flask
      experiments using algal and cyanobacterial pure cultures, and field trials on
      five common eubacterial probes: S-D-Bact-008-a-A-19, S-D-Bact-338-a-A-18, S-D
      Bact-785-a-A-19, S-D-Bact-927-a-A-17, and S-D-Bact-1088-a-A-20. The database
      search and laboratory tests showed significant potential for binding among most
      bacterial probes and organelle ssu-rRNA. However, we propose two probing
      strategies to overcome this problem. First, one could use Bact-785 and Bact-338
      in tandem, with the plastid component being estimated as the difference between
      the two signals (Bact-338 has approximately 70% overlap with known plastid
      sequences). Alternately, one might use Bact-338 as the primary eubacterial probe,
      but then use Cyan-785-a-A-19 (a probe that binds significantly to plastid rRNA)
      to correct for the plastid-associated false-positive signal. Both strategies
      would use a eukaryotic probe (S-D-Euca-1379-a-A-16) and Cyan-785-b-A-19 (a probe
      for most cyanobacteria) to further segregate rRNA signals. Trials were
      successfully performed using the strategies on samples from a recent field study.

PMID- 14967224
TI  - Rapid estimation of lipids in oleaginous fungi and yeasts using Nile red
      fluorescence.
AB  - A rapid estimation method of the intracellular lipid content in microorganisms
      using a fluorescent probe, Nile red, was established by optimization of the Nile
      red staining and data processing. The protocol was designed to be applicable to a
      wide range of microorganisms and culture conditions. In the optimized procedure,
      cells diluted with buffer were stained with 0.24-0.47 microg/ml of Nile red for 5
      min, and the fluorescent emission spectra in the wavelength region of 400 to 700
      nm excited at 488 nm were acquired before and after the Nile red addition. The
      fluorescence intensity corresponding to the intracellular lipid amount was
      determined at the peak of the corrected spectrum. The value showed a linear
      relation with the lipid content of various oleaginous fungi and yeasts measured
      by the conventional method. The relative intensities against the unit lipid
      amounts were almost similar except for one yeast. For the application to mycelia
      forming various types of pellets, a simple and easy pretreatment of shaking with
      glass beads for 5-10 min was added to the protocol. The established method was
      applicable to estimate the lipid content of a wide range of microorganism
      cultures containing 2-5000 microg-lipid/ml-broth.

PMID- 14967225
TI  - Comparison of methods to detect biosurfactant production by diverse
      microorganisms.
AB  - Three methods to detect biosurfactant production, drop collapse, oil spreading,
      and blood agar lysis, were compared for their ease of use and reliability in
      relation to the ability of the cultures to reduce surface tension. The three
      methods were used to test for biosurfactant production in 205 environmental
      strains with different phylogenetic affiliations. Surface tension of select
      strains that gave conflicting results with the above three methods was also
      measured. Sixteen percent of the strains that lysed blood agar tested negative
      for biosurfactant production with the other two methods and had little reduction
      in surface tension (values above 60 mN/m). Thirty eight percent of the strains
      that did not lyse blood agar tested positive for biosurfactant production with
      the other two methods and had surface tension values as low as 35 mN/m. There was
      a very strong, negative, linear correlation between the diameter of clear zone
      obtained with the oil spreading technique and surface tension (rs = -0.959) and a
      weaker negative correlation between drop collapse method and surface tension (rs
      = -0.82), suggesting that the oil spreading technique better predicted
      biosurfactant production than the drop collapse method. The use of the drop
      collapse method as a primary method to detect biosurfactant producers, followed
      by the determination of the biosurfactant concentration using the oil spreading
      technique, constitutes a quick and easy protocol to screen and quantify
      biosurfactant production. The large number of false negatives and positives
      obtained with the blood agar lysis method and its poor correlation to surface
      tension (rs = -0.15) demonstrated that it is not a reliable method to detect
      biosurfactant production.

PMID- 14967226
TI  - Evaluation of double formalin--Lugol's fixation in assessing number and biomass
      of ciliates: an example of estimations at mesoscale in NE Atlantic.
AB  - Ciliated protozoa are potential grazers of primary and bacterial production and
      act as intermediaries between picoplankton and copepods and other large
      suspension feeders. Accurate determination of ciliate abundance and feeding mode
      is crucial in oceanic carbon budget estimations. However, the impact of different
      fixatives on the abundance and cell volume of ciliates has been investigated in
      only a few studies using either laboratory cultures or natural populations.
      Lugol's solution and formalin are the most commonly used fixatives for the
      preservation of ciliates samples. In the present study, the aim was to compare
      0.4% Lugol's solution and 2% borated-formalin fixation and evaluate the need of
      counting duplicate samples each using a different fixative. For this, a large
      number of samples (n = 110) from the NE Atlantic was analyzed in the frame of
      POMME program (Multidisciplinary Mesoscale Ocean Program). We established a
      statistically significant relationship (p < 0.0001) between Lugol's and formalin
      fixed samples for both abundance (r2 = 0.50) and biomass (r2 = 0.76) of aloricate
      ciliates which showed that counts were higher in Lugol's solution by a factor of
      2 and a non-taxon specific cell-loss in formalin. However, loricate ciliate
      abundance in our samples which were represented primarily by Tintinnus spp. did
      not show any difference between the two treatments. Abundance and biomass of
      mixotrophic ciliates (chloroplast-bearing cells) were for various reasons
      underestimated in both treatments. Our results show that unique fixation by
      formalin may severely underestimate ciliates abundance and biomass although their
      population may not alter. For this reason, Lugol's solution is best for the
      estimation of their abundance and biomass. However, for counts of mixotrophs and
      the evaluation of the ecological role of ciliates in carbon flux, double fixation
      is essential. Compromises regarding the fixatives have lead to severe
      underestimations of mixotrophs in studies conducted by now.

PMID- 14967227
TI  - A novel tri-primer PCR method (TP-PCR) for rapid construction of fpg gene.
AB  - A novel tri-primer polymerase chain reaction method (TP-PCR) was developed for
      the construction of a fused fpg gene, in which no endonuclease and ligase were
      used. Instead, two templates and three specifically designed primers were
      applied. Results showed that pheB and gfp genes, which encodes the catechol 2, 3
      dioxygenase and the green fluorescent protein (GFP), respectively, were
      successfully fused into an fpg gene through the rapid TP-PCR system, indicating
      that TP-PCR method could be a useful tool for DNA fragment fusion in which no
      proper endonuclease sites were available.

PMID- 14967228
TI  - Comparison of RNA- and DNA-based species diversity investigations in rhizoplane
      bacteriology with respect to chloroplast sequence exclusion.
AB  - Comparative sequence analysis of 16S rDNA genes is a popular method of
      investigating microbial communities but problems arise when the subjects are
      rhizoplane consortia. The culture independent direct isolation of DNA from root
      sample results in huge amounts of plant DNA, and the universal primers designed
      for the domain Bacteria will amplify chloroplast ribosomal genes as well. A clone
      library generated from such a PCR product will be dominated by chloroplast, and
      the emulation of numerous chloroplasts and rhizoplane bacterial 16S rDNA for
      primers also distorts the results of different fingerprinting analyses. To
      resolve this problem, a new approach has been developed. The ribosome content is
      correlated with the metabolic activity of cells; therefore, RNA-based methods
      seem to be appropriate to exclude cell organelles (e.g. chloroplast) and dormant
      bacterial cells. A rapid RNA isolation and a reliable reverse transcription (RT)
      PCR method were developed to investigate rhizoplane bacterial community and the
      results were compared with a total DNA isolation-based method of the same sample.
      16S rRNA and DNA PCR products were cloned and screened by restriction analysis.
      The relative abundance of chloroplast amplicons in DNA and RNA clone libraries
      was compared and a significant decrease was detected (from 63% and 71% to 1% and
      7%, respectively).

PMID- 14967229
TI  - Development of a plate technique for screening of polysaccharide-degrading
      microorganisms by using a mixture of insoluble chromogenic substrates.
AB  - A plate assay based on the visible solubilization of small substrate particles
      and the formation of haloes on Petri dishes, containing a mixture of different
      dye-labelled polysaccharides as substrates, provides a specific, reliable and
      rapid simultaneous detection of corresponding polysaccharide-degrading
      microorganisms. It has potential for increasing the efficacy of screening of
      microorganisms, utilizing different polysaccharides, in large numbers of natural
      samples. Diversely colored insoluble forms of amylose, xylan and hydroxyethyl
      cellulose (HE-cellulose) were prepared as chromogenic substrates by using the
      cross-linking reagent 1,4-butanediol diglycidyl ether and the dyes Brilliant Red
      3B-A, Cibacron Blue 3GA and Reactive Orange 14. Using the method, the bacteria
      with amylase or xylanase or cellulase or a combination of these activities were
      screened from soil and sludge samples, selected and identified according to 16S
      rDNA sequencing.

PMID- 14967230
TI  - gyrB as a phylogenetic discriminator for members of the Bacillus anthracis-cereus
      thuringiensis group.
AB  - Bacillus anthracis, the causative agent of the human disease anthrax, Bacillus
      cereus, a food-borne pathogen capable of causing human illness, and Bacillus
      thuringiensis, a well-characterized insecticidal toxin producer, all cluster
      together within a very tight clade (B. cereus group) phylogenetically and are
      indistinguishable from one another via 16S rDNA sequence analysis. As new
      pathogens are continually emerging, it is imperative to devise a system capable
      of rapidly and accurately differentiating closely related, yet phenotypically
      distinct species. Although the gyrB gene has proven useful in discriminating
      closely related species, its sequence analysis has not yet been validated by
      DNA:DNA hybridization, the taxonomically accepted "gold standard". We
      phylogenetically characterized the gyrB sequences of various species and
      serotypes encompassed in the "B. cereus group," including lab strains and
      environmental isolates. Results were compared to those obtained from analyses of
      phenotypic characteristics, 16S rDNA sequence, DNA:DNA hybridization, and
      virulence factors. The gyrB gene proved more highly differential than 16S, while,
      at the same time, as analytical as costly and laborious DNA:DNA hybridization
      techniques in differentiating species within the B. cereus group.

PMID- 14967231
TI  - Detection of PCR amplicons from bacterial pathogens using microsphere
      agglutination.
AB  - For rapid and inexpensive detection of polymerase chain reaction (PCR) amplicons,
      a novel microsphere agglutination assay has been developed. PCR is carried out
      using biotinylated forward and reverse primers, and the amplified DNA fragments
      are able to agglutinate streptavidin-coated microspheres (5.7 microm in
      diameter). Purification of PCR amplicons is unnecessary when initial primer
      concentrations are 250 nM. Agglutination can be identified visually within 2 min
      without any additional equipment or reagents. Using listeriolysin (lisA)-specific
      biotinylated primers, we have successfully detected and identified Listeria
      monocytogenes lisA+ cells among Salmonella typhimurium, Staphylococcus aureus,
      Campylobacter jejuni and Escherichia coli O157:H7 cells. The simplicity of this
      protocol considerably reduces the time and cost of diagnostic PCR experiments.
      This procedure is potentially useful for various studies and field applications.

PMID- 14967232
TI  - Expression of green fluorescent protein and its application in pathogenesis
      studies of serotype 2 Streptococcus suis.
AB  - We investigated the interaction between type 2 Streptococcus suis and swine
      phagocytes during infection of the natural host, by using green fluorescent
      protein (GFP) as a specific marker to observe the challenge organism. We compared
      the strength of the S. suis sly promoter (SP332) and the synthetic promoter
      (CP25) in driving GFP expression. Two GFP alleles, gfpP11 and gfpmut3*, were also
      compared. The two promoters and two alleles were efficiently compared using three
      different promoter-GFP gene combinations on a shuttle vector, which were
      transformed into S. suis strains SX332, SX932 or M2. Plasmid pSL6.81 has SP332
      with gfpP11, pSL5.24 has SP332 with gfpmut3*, and pSL5.28 has CP25 with gfpmut3*.
      The transformants were fluorescent with green light when viewed with an
      epifluorescence microscope or during flow cytometry. The signal was also detected
      using a laser scanning confocal microscope. The GFP expression level varied and
      CP25 with gfpmut3* led to greatest expression. For optimizing GFP detection,
      fluorescence-based cell sorting was applied to SX332(pSL5.28) and the mean
      fluorescence intensity increased 25.9% after optimization. Fluorescence activated
      cell sorting (FACS)-based phagocytosis assay showed that, without opsonization,
      phagocytosis rates of SX332, SX932 and M2 by both neutrophils and monocytes were
      similar and low. After opsonization, the phagocytosis of M2 increased 10-fold
      while phagocytosis of SX332 and SX932 did not change. GFP-labeled S. suis was
      identified in fresh pig tonsil tissue 18 h after infection. The results of this
      study indicated that GFP was expressed in type 2 S. suis and GFP labeled S. suis
      could be used in phagocytosis and pathogenesis studies.

PMID- 14967233
TI  - Identification of microorganisms by PCR amplification and sequencing of a
      universal amplified ribosomal region present in both prokaryotes and eukaryotes.
AB  - The small ribosomal subunit contains 16S rRNA in prokaryotes and 18S rRNA in
      eukaryotes. Even though it has been known that some small ribosomal sequences are
      conserved in 16S rRNA and 18S rRNA molecules, they have been used separately for
      taxonomic and phylogenetic studies. Here, we report the existence of two highly
      conserved ribosomal sequences in all organisms that allow the amplification of a
      zone containing approximately 495 bp in prokaryotes and 508 bp in eukaryotes
      which we have named the "Universal Amplified Ribosomal Region" (UARR).
      Amplification and sequencing of this zone is possible using the same two
      universal primers (U1F and U1R) designed on the basis of two highly conserved
      ribosomal sequences. The UARR encompasses the V6, V7 and V8 domains from SSU rRNA
      in both prokaryotes and eukaryotes. The internal sequence of this zone in
      prokaryotes and eukaryotes is variable and the differences become less marked on
      descent from phyla to species. Nevertheless, UARR sequence allows species from
      the same genus to be differentiated. Thus, by UARR sequence analysis the
      construction of universal phylogenetic trees is possible, including species of
      prokaryotic and eukaryotic microorganisms together. Single isolates of
      prokaryotic and eukaryotic microorganisms from different sources can be
      identified by amplification and sequencing of UARR using the same pair of primers
      and the same PCR and sequencing conditions.

PMID- 14967234
TI  - Purification of Toxoplasma gondii oocysts by cesium chloride gradient.
AB  - We describe the use of a cesium chloride (CsCl) gradient as an improvement for
      the purification of Toxoplasma gondii oocysts from concentrated suspensions.
      After concentration by sucrose flotation, this technique gives a > 96% recovery
      of very pure unsporulated or sporulated oocysts, but requires "fresh" oocysts (<
      or = 10 weeks of age). This material is suitable for biochemical and
      immunological analyses of environmentally resistant T. gondii oocysts.

PMID- 14967235
TI  - A rapid DNA extraction method for PCR identification of fungal indoor air
      contaminants.
AB  - Following air sampling fungal DNA needs to be extracted and purified to a state
      suitable for laboratory use. Our laboratory has developed a simple method of
      extraction and purification of fungal DNA appropriate for enzymatic manipulation
      and Polymerase Chain Reaction (PCR) applications. The methodology described is
      both rapid and cost effective for use with multiple fungal organisms.

PMID- 14967236
TI  - Conformational sampling for the impatient.
AB  - Several new methods for sampling conformations of biomolecules have appeared
      recently. A brief review thereof is presented, with particular emphasis on
      applications that have been published, and suitability for different kinds of
      systems. Four methods (namely: RESPA, replica-exchange molecular dynamics,
      CONCOORD and Gaussian network method) are readily applicable for biomolecular
      systems.

PMID- 14967237
TI  - Ligand trapping in epithelial layers and cell cultures.
AB  - We analyze a stochastic model that describes receptor-mediated ligand trapping in
      epithelial layers and cell culture assays. In both cases, the problem is reduced
      to diffusion of a Brownian particle between the partially absorbing and
      reflective surfaces. We derive an analytical expression for the spatial
      distribution of the trapping points and identify the domains of applicability of
      the two limiting regimes. We conclude that a thin layer approximation is
      applicable for ligand trapping in epithelial layers while a typical cell culture
      experiment is appropriately described within an infinite layer approximation.

PMID- 14967238
TI  - EXAFS studies of structural changes in fragile glasses of zinc nitrate and nickel
      nitrate hydrates.
AB  - The ionic structures of aqueous solutions of two sets of transition metal
      nitrates have been studied in the liquid and glass states by EXAFS spectroscopy.
      Experiments were carried out on Zn(NO3)2.xH2O, with x=2, 6, 12 and NiNO.9HO over
      the temperature range 30<T(K)<250. The glass transition regime was monitored by
      means of an in-situ DSC probe. The EXAFS data were analysed by recently developed
      Monte Carlo procedures, enabling a discussion of the glass structure in terms of
      pairwise and higher order correlations. Results for the zinc nitrate hydrates
      show complex behaviour depending on the concentration. This behaviour is
      explained in terms of first hydration shell stability and NO3- penetration. This
      result contrasts with that for the equivalent correlation in nickel nitrate, and
      is taken as evidence for a more extensive free energy landscape of zinc nitrate
      hydrates. The results are also consistent with the known hydration properties of
      Zn2+ and Ni2+, and help explain why Zn2+ is biologically active in solution.

PMID- 14967239
TI  - Requirements for generating sigmoidal time-course aggregation in nucleation
      dependent polymerization model.
AB  - Requirements for generating remarkable sigmoidal time-course of aggregation are
      found in the nucleation-dependent polymerization model by a numerical calculation
      method; i.e. there are optimum values of the kinetic constants to afford
      prominent sigmoidal character by inducing slightly unfavorable nucleation.
      However, if the nucleus formation is too unfavorable, sigmoidal character is
      again decreased. This result is in contrast to the generally accepted idea that
      sigmoid is induced by thermodynamically unfavorable nucleation phase.

PMID- 14967240
TI  - Line shape analyses for water 17O NMR quintet observed in a bacteriophage Pf1
      solution at different temperatures.
AB  - Partially resolved 17O NMR quintet was observed in a filamentous bacteriophage
      Pf1 solution at 70 degrees C with a quadrupole splitting approximately 100 Hz. As
      the temperature decreased, the resolution was reduced but the line shapes were
      still indicative of residual quadrupole splitting. Line shape analyses were
      performed using the quadrupolar relaxation theory for spin 5/2. The contribution
      to the residual quadrupole splitting from the electric field gradients stemming
      from the phage filaments, which were oriented in the magnet, was taken into
      account. As a result, the observed 17O spectra at different temperatures were
      simulated and the hydration number of the phage DNA was determined.

PMID- 14967241
TI  - Role of non-covalent interactions for determining the folding rate of two-state
      proteins.
AB  - Understanding the factors influencing the folding rate of proteins is a
      challenging problem. In this work, we have analyzed the role of non-covalent
      interactions for the folding rate of two-state proteins by free-energy approach.
      We have computed the free-energy terms, hydrophobic, electrostatic, hydrogen
      bonding and van der Waals free energies. The hydrophobic free energy has been
      divided into the contributions from different atoms, carbon, neutral nitrogen and
      oxygen, charged nitrogen and oxygen, and sulfur. All the free-energy terms have
      been related with the folding rates of 28 two-state proteins with single and
      multiple correlation coefficients. We found that the hydrophobic free energy due
      to carbon atoms and hydrogen-bonding free energy play important roles to
      determine the folding rate in combination with other free energies. The
      normalized energies with total number of residues showed better results than the
      total energy of the protein. The comparison of amino acid properties with free
      energy terms indicates that the energetic terms explain better the folding rate
      than amino acid properties. Further, the combination of free energies with
      topological parameters yielded the correlation of 0.91. The present study
      demonstrates the importance of topology for determining the folding rate of two
      state proteins.

PMID- 14967242
TI  - Studies of interaction between poly(allylamine hydrochloride) and double helix
      DNA by spectral methods.
AB  - DNA interaction with cationic polyelectrolytes promises to be a versatile and
      effective synthetic transfection agent. This paper presents the study on
      interaction between a simple artificial cationic polymer, poly(allylamine
      hydrochloride) (PAA), and herring sperm DNA (hsDNA) using several spectroscopic
      methods, including light scattering, microscopic FTIR-, CD-spectroscopy and so
      on. The results show that PAA interacts with DNA through both the phosphate
      groups and the nitrogenous bases of DNA. The formation of DNA/PAA complex may
      change the micro-environment of double helix of DNA from B- to C-form and the
      great changes in DNA morphology occur when N:P ratio is near to 1.0. At the same
      time, the spectroscopic changes of ethidium bromide (EB) on its binding to DNA
      are utilized to study the interaction between PAA and DNA. Reversion of the
      maximum absorption wavelength (numax), reduction of induced circular dichroism
      and decrease in fluorescence intensity of DNA-EB on addition of PAA indicate that
      the formation of the complex between DNA and PAA is not in favor of the
      interaction between DNA and EB. The binding constant of EB and the number of
      binding sites per nucleotide decrease with increase in the concentrations of PAA,
      indicating noncompetitive inhibition of EB binding to DNA in the presence of PAA.
      It is also proved that the formation of the DNA/PAA complex is influenced by pH
      value and ionic strength.

PMID- 14967243
TI  - Transition from contractile to protractile distortions occurring along an actin
      filament sliding on myosin molecules.
AB  - An ATP-activated actin filament sliding on myosin molecules exhibited mechanical
      distortions or fluctuations both longitudinally and transversally along the
      filament. Although actin filaments exhibited a uniform sliding movement
      longitudinally as the ATP concentration increased, the longitudinal fluctuations
      were found to vary their magnitude with the concentration. The magnitude of
      longitudinal fluctuations reached its maximum at approximately 100 microM of the
      ATP concentration. The local enhancement of the longitudinal fluctuations as
      responding to changes in the ATP concentration is associated with a critical
      phenomenon bridging the two different kinds of mechanical distortions, either
      contractile or protractile ones, occurring within a sliding actin filament.

PMID- 14967244
TI  - Effect of alcohols on aqueous lysozyme-lysozyme interactions from static light
      scattering measurements.
AB  - Alcohols have been widely used as protein denaturants, precipitants and
      crystallization reagents. We have studied the effect of alcohols on aqueous hen
      egg lysozyme self-interactions by measuring the osmotic second virial coefficient
      (B22) using static light scattering. Addition of alcohols increases B22,
      indicating stronger protein-protein repulsion or weaker attraction. For the
      monohydric alcohols used in this study (methanol, ethanol, 1-propanol, n-butanol,
      iso-butanol and trifluoroethanol), B22 for lysozyme reaches a common plateau at
      approximately 5% (v/v) alcohol, while glycerol increases B22 more than monohydric
      alcohols. For a 0.05 M NaCl hen-egg lysozyme solution at pH 7, B22 increases from
      2.4 x 10(-4) to 4.7 x 10(-4) ml mol/g2 upon addition of monohydric alcohols and
      to 5.8 x 10(-4) ml mol/g2 upon addition of glycerol. We describe the alcohol
      effect using a simple model that supplements the DLVO theory with an additional
      alcohol-dependent term representing orientation-averaged hydrophobic
      interactions. In this model, the increased lysozyme repulsive forces in the
      presence of monohydric alcohols are interpreted in terms of adsorption of alcohol
      molecules on hydrophobic sites on the protein surface. This adsorption reduces
      attractive hydrophobic protein-protein interactions. A thicker lysozyme hydration
      layer in aqueous glycerol solution can explain the glycerol-increased lysozyme
      lysozyme repulsion.

PMID- 14967245
TI  - Effects of inert volume-excluding macromolecules on protein fiber formation. II.
      Kinetic models for nucleated fiber growth.
AB  - A sequential model for nucleated protein fiber formation is proposed that is
      similar in broad outline to models proposed previously (Thermodynamics of the
      Polymerization of Protein, Academic Press, New York, (1975); Biophys. J. 50
      (1986) 583) but generalized to allow for thermodynamic nonideality resulting from
      a high degree of volume occupancy by inert macromolecular cosolutes
      (macromolecular crowding). The effect of volume occupancy on the rate of fiber
      formation is studied in the transition-state rate-limited regime through
      systematic variation of rate-limiting step (prenuclear oligomer formation,
      nucleus formation or fiber growth), shape of prenuclear oligomer, size of
      nucleus, extent of reversibility, nature of inert cosolute (hard globular
      particle or random coil polymer) and size of inert cosolute relative to that of
      fiber-forming protein. It is found that crowding can accelerate the rate of fiber
      formation by as much as several orders of magnitude. The extent of acceleration
      for a given degree of volume occupancy depends upon several factors, the most
      conspicuous of which is the stoichiometry of the nucleus. In contrast, the rate
      of redistribution of fiber length, which occurs on a much slower time scale than
      polymer formation, is found to be insensitive to the extent of crowding.

PMID- 14967246
TI  - Reappraisal of disparities between osmolality estimates by freezing point
      depression and vapor pressure deficit methods.
AB  - As a response to recent expression of concern about possible unreliability of
      vapor pressure deficit measurements (K. Kiyosawa, Biophys. Chem. 104 (2003) 171
      188), the results of published studies on the temperature dependence of the
      osmotic pressure of aqueous polyethylene glycol solutions are shown to account
      for the observed discrepancies between osmolality estimates obtained by freezing
      point depression and vapor pressure deficit osmometry--the cause of the concern.

PMID- 14967248
TI  - The problem with pupils.

PMID- 14967249
TI  - Pseudophakic retinal detachment after Nd:YAG capsulotomy.

PMID- 14967250
TI  - New iridectomy technique for phakic IOL implantation.

PMID- 14967251
TI  - Aqueous and vitreous penetration of topically applied ciprofloxacin and
      ofloxacin.

PMID- 14967253
TI  - Secondary anterior chamber intraocular lenses.

PMID- 14967254
TI  - Consultation section: refractive surgical problems.

PMID- 14967263
TI  - Three-step technique for staining the anterior lens capsule with indocyanine
      green or trypan blue.
AB  - A 3-step technique for staining the anterior lens capsule was developed to
      optimize the use of a capsule dye (trypan blue or indocyanine green) during
      capsulorhexis. After the injection of a viscoadaptive ophthalmic viscosurgical
      device (OVD) (sodium hyaluronate 2.3% [Healon 5]), which fills the anterior
      chamber, balanced salt solution (BSS) is gently injected onto the anterior
      capsule, creating a wafer-thin, fluid-filled space beneath the OVD. The dye is
      slowly injected through a 27-gauge cannula (Duckworth & Kent), selectively mixing
      with the BSS and allowing relatively accurate painting of the anterior capsule,
      approximating the size and shape of the intended capsulorhexis. This 3-step
      technique avoids the use of air as well as the uncontrolled dispersion and
      excessive accumulation of dye within the OVD.

PMID- 14967264
TI  - Maximum permissible torsional misalignment in aberration-sensing and wavefront
      guided corneal ablation.
AB  - PURPOSE: To determine the maximum permissible torsional misalignment in wavefront
      guided refractive surgery. SETTING: University of Zurich, Department of
      Ophthalmology, Zurich, Switzerland. METHODS: The effect of torsionally misaligned
      ablations on the optical outcome was simulated using measured wavefront
      aberration patterns (2nd to 6th orders) in 130 normally aberrated eyes. The
      calculations were done for 3.0 mm, 5.0 mm, and 7.0 mm pupils. The optical quality
      of the simulated correction was rated by the root-mean-square residual wavefront
      error. RESULTS: The required accuracy of torsional alignment is higher for the
      correction of higher-order aberrations than for cylindrical treatments only. To
      improve the optical performance to the level of the best 10% of a normal,
      untreated population, ablation would have to occur within a tolerance range of
      4.0 degrees for 7.0 mm pupils. CONCLUSIONS: The tolerance range for torisional
      alignment in wavefront-guided higher-order corrections depends on the amount of
      original optical error in each eye. Rough centration based on the surgeon's
      judgment may not be accurate enough to achieve significantly improved optical
      quality in a high percentage of treated eyes.

PMID- 14967265
TI  - Flap dimensions created with the IntraLase FS laser.
AB  - PURPOSE: To assess the safety and predictability of the IntraLase femtosecond
      laser to create accurate flap thickness and diameter. SETTING: Clinical office
      based practice. METHODS: In the first 103 eyes in which flaps were created with
      the IntraLase laser, the flap thickness was measured by the ultrasonic difference
      between the preoperative and post-flap-creation central corneal thickness and the
      flap diameter was measured with calipers. RESULTS: As the attempted flap
      thickness decreased from 140.0 microm to 110.0 microm in 10.0 microm increments,
      the mean flap thickness decreased from 132.5 microm to 125.0 microm, with
      standard deviations decreasing from +/-18.5 to +/-12.0 microm. The mean flap
      diameter differed from the attempted diameter by less than 0.03 microm in all but
      the 130.0 microm group. Two slipped flaps and 20 cases of interface inflammation
      occurred early in the series. CONCLUSIONS: The IntraLase laser, while adding
      technical complexity to the laser in situ keratomileusis procedure, is able to
      predictably create flap diameters, hinge location, and flap thickness while
      eliminating the risk for cap perforations. The technique of flap elevation
      affects rapidity of visual recovery.

PMID- 14967266
TI  - Phakic intraocular lenses to correct high myopia: Adatomed, Staar, and Artisan.
AB  - PURPOSE: To evaluate the feasibility and safety of using phakic intraocular
      lenses (IOLs) to correct high myopia by comparing 3 IOL models: Adatomed, Staar,
      and Artisan. SETTING: La Fe University Hospital, Department of Ophthalmology, and
      the Fundacion Oftalmologica del Mediterraneo, Valencia, Spain. METHODS: In this
      prospective comparative study, a phakic IOL was implanted in 217 highly myopic
      eyes (118 patients). Fifty-nine eyes received an Adatomed IOL, 21 eyes a Staar
      IOL, and 137 eyes an Artisan IOL. The mean preoperative spherical equivalent was 
      15.39 diopters (D) +/- 2.83 (SD), -16.00 +/- 5.05 D, and -16.17 +/- 2.75 D in the
      Adatomed, Staar, and Artisan groups, respectively. The mean follow-up was 32.4
      months (range 19 to 46 months) in the Adatomed group, 18.3 months (range 11 to 21
      months) in the Staar group, and 121.4 months (range 38.4 to 154.3 months) in the
      Artisan group. At the follow-up examinations, intraocular pressure (IOP), IOL
      pigment deposits, cataract formation, and visual acuity were evaluated. RESULTS:
      The best corrected and uncorrected visual acuities improved in all eyes. No
      significant differences in visual acuity improvement were observed with the 3
      materials, although the improvement was somewhat greater in eyes with the Artisan
      and Staar IOLs. The difference in mean IOP between preoperatively and the last
      follow-up examination was 1.5 mm Hg in the Staar group, 1.3 mm Hg in the Adatomed
      group, and 1.7 mm Hg in the Artisan group (P =.36, P =.26, and P =.32,
      respectively). The incidence of pigment deposits was similar in the Adatomed and
      Staar groups, with deposits in 32 eyes (54.23%) and 8 eyes (38.1%), respectively.
      Anterior cataract formation was higher in the Adatomed group (44.06%) than in the
      Staar group (9.52%); nuclear cataract developed in 2 Adatomed eyes (1.46%) only.
      CONCLUSIONS: There was a higher incidence of anterior subcapsular cataract
      formation in the Adatomed group than in the Staar group. Delayed cataract
      development and the cataract type in patients with Artisan IOLs indicate that age
      and axial length may be prognostic factors. Factors such as IOL design, material,
      and placement probably affect cataract formation in eyes with posterior chamber
      IOLs for high myopia, particularly the Adatomed IOL.

PMID- 14967267
TI  - Effect of haptic design on change in axial lens position after cataract surgery.
AB  - PURPOSE: To compare the postoperative changes in anterior chamber depth (ACD)
      between single-piece and multipiece AcrySof intraocular lenses (IOLs) (Alcon
      Laboratories, Inc.) and their effect on the postoperative refractive shift.
      SETTING: Department of Ophthalmology, University of Vienna, Vienna, Austria.
      METHODS: This prospective randomized bilateral study with intraindividual
      comparison comprised 104 eyes of 52 consecutive patients with age-related
      cataract. All patients had standardized cataract surgery with a temporal self
      sealing incision, phacoemulsification, and IOL implantation in the capsular bag.
      The first 30 patients received a single-piece, 5.5 mm optic IOL (AcrySof SA30) in
      1 eye and a multipiece IOL (AcrySof MA30) in the other eye. Another 22 patients
      received the corresponding 6.0 mm optic models (AcrySof SA60 and AcrySof MA60,
      respectively). Anterior chamber depth measurements and evaluation of the change
      in ACD during the first 6 postoperative months were performed using partial
      coherence laser interferometry. The amount of change in capsulorhexis size during
      the first 6 postoperative months was assessed using standardized
      retroillumination photographs. RESULTS: Single-piece IOLs shifted significantly
      less postoperatively than multipiece IOLs. The multipiece IOLs shifted forward,
      especially from 1 day to 1 month. The change in the capsulorhexis area was
      similar between IOL types. CONCLUSIONS: Single-piece AcrySof IOLs shifted
      minimally after the first postoperative day; therefore, the prescription for
      spectacles in eyes with this IOL can be obtained soon after surgery.

PMID- 14967268
TI  - Effect of optic edge design and haptic angulation on postoperative intraocular
      lens position change.
AB  - PURPOSE: To assess the effect of optic edge design and optic-haptic angulation of
      open-loop intraocular lenses (IOLs) on postoperative axial movement and the final
      position of the optic by measuring the anterior chamber depth (ACD) during the
      first postoperative year using partial coherence interferometry (PCI). SETTING:
      Department of Ophthalmology, Vienna General Hospital, Institute of Medical
      Physics, University of Vienna, Vienna, Austria. METHODS: In study 1, a 3-piece
      silicone IOL with nonangulated modified C-loop haptics (MicroSil, Dr. Schmidt)
      was implanted in 78 eyes of 39 patients; patients were randomized to receive a
      round-edged optic IOL in 1 eye and a sharp-edged optic IOL in the other eye. The
      ACD was measured by PCI 1 day, 1 week, 3 months, and 1 year after surgery. In
      study 2, a foldable, 3-piece acrylic IOL with modified 10-degree angulated J-loop
      haptics (AcrySof MA60BM, Alcon) was implanted in 32 eyes of 32 patients. The ACD
      was measured by PCI 1 day, 1 week, and 3 months after surgery. RESULTS: In eyes
      with a nonangulated silicone IOL, there was a significant postoperative change in
      ACD with both sharp-edged and round-edged designs (P<.01). There was forward
      movement of both IOL designs in the first week, with no significant difference
      between the 2 models. From 1 week to 3 months, there was backward movement of
      IOLs of both designs, with the sharp-edged IOL moving a significantly greater
      amount (P<.001). From 3 months to 1 year, IOLs with both optic edge designs moved
      slightly backward. Sixty-six percent of angulated IOLs showed continuous but
      variable forward movement and 34%, backward movement. CONCLUSIONS: Optic edge
      design influenced postoperative axial optic movement and thus had an impact on
      the development of postoperative refraction (refractive shift, deviation from
      target refraction). The influence of optic-haptic angulation proved to be
      significantly greater and more variable than edge design.

PMID- 14967269
TI  - Retinal breaks and detachment after neodymium: YAG laser posterior capsulotomy:
      five-year incidence in a prospective cohort.
AB  - PURPOSE: To determine the 5-year incidence of retinal breaks and retinal
      detachment (RD) after neodymium:YAG (Nd:YAG) laser posterior capsulotomy and the
      prophylactic treatment of perioperative retinal breaks. SETTING: Department of
      Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. METHODS:
      This study design was stage 2 of a prospective nonrandomized interventional case
      series. Of 341 patients (350 eyes) referred for a first Nd:YAG laser posterior
      capsulotomy between October 1994 and February 1996, 211 (220 eyes) were examined
      for retinal breaks before and after capsulotomy (stage 1 of study). Asymptomatic
      breaks were prophylactically photocoagulated. Of the 211 patients, 106 (113 eyes)
      were examined at stage 2 a median of 4.9 years after Nd:YAG capsulotomy. The
      charts of all 341 patients were reviewed for development of RD and retinal
      breaks. The proportion of patients developing RD was estimated by Kaplan-Meier
      survival analysis, and the risk for RD was modeled by Cox proportional hazard
      regression. RESULTS: By 5 years, the overall cumulative proportion of RD in the
      341 patients was 2.0% (95% confidence interval [CI], 1.0-4.0). Of the 211 eyes
      enrolled in stage 1, 2 (1.2%) developed an RD (95% CI, 0.3-4.7). Of 51 fellow
      eyes that had a capsulotomy and 120 eyes that had a capsulotomy but were not
      enrolled in stage 1 and were not prophylactically treated, RD occurred in 6 eyes
      (5.8%; 95% CI, 2.6-13). By univariate Cox regression, the axial length, whether
      modeled as a continuous variable (hazard ratio [HR] 1.51 for each millimeter
      increase) or categorized using 25.0 mm as a cutoff (HR 11.1), had the strongest
      association with RD after Nd:YAG posterior capsulotomy (P =.0002 and P =.0016,
      respectively). CONCLUSIONS: In addition to the capsulotomy, other known risk
      factors predicted RD after Nd:YAG laser posterior capsulotomy. Close follow-up
      and prophylactic photocoagulation of preexisting retinal breaks are worth
      considering, especially in high-risk eyes.

PMID- 14967270
TI  - Tissue damage at anterior capsule edges after continuous curvilinear
      capsulorhexis, high-frequency capsulotomy, and erbium:YAG laser capsulotomy.
AB  - PURPOSE: To compare the effect of erbium:YAG laser photocapsulotomy (ELC),
      continuous curvilinear capsulorhexis (CCC), and high-frequency capsulotomy (HFC)
      on anterior capsule edges using light microscopy (LM) and transmission electron
      microscopy (TEM). SETTING: Department of Ophthalmology, Department of Histology
      and Embryology II, University of Vienna, Vienna, Austria. METHODS: Five anterior
      capsule membranes were obtained experimentally by ELC, which was performed with
      the Oertli MicroLaser photoemulsification tip in eyes from 5 human cadavers.
      Thirty anterior capsule membranes were obtained during cataract surgery by CCC (n
      = 15) or, in cases with poor or missing red fundus reflexes, by HFC (n = 15).
      Continuous curvilinear capsulorhexis was performed conventionally with a manual,
      bent, 27-gauge cannula, and HFC was performed according to Kloti. Membranes were
      processed and examined by LM and TEM according to standard procedures. RESULTS:
      The edges obtained by ELC showed mild signs of denaturation and mechanical
      disruption, tears, and micro-tears. Lens capsule edges obtained by CCC were
      smooth with no irregularities in any specimen; the edges were beveled anteriorly
      to posteriorly with no evidence of tearing. Edges produced by HFC were
      considerably wider; the surfaces showed distinct denaturation, preformed tears,
      and micro-tears. The edges were surrounded by a nonhomogeneous mass, which
      consisted mainly of denatured lens capsule material. CONCLUSIONS: Of the 3
      techniques, CCC produced the mildest tissue damage. The histological damage at
      ELC edges was relatively mild and intermediate compared with that seen at CCC and
      HFC edges. These observations suggest that ELC is an appropriate option for
      anterior capsulotomy in cataract surgery.

PMID- 14967271
TI  - Laser-assisted subepithelial keratectomy and photorefractive keratectomy versus
      conventional treatment of myopic anisometropic amblyopia in children.
AB  - PURPOSE: To evaluate the visual and refractive results of photorefractive
      keratectomy (PRK) and laser-assisted subepithelial keratectomy (LASEK) for high
      myopic anisometropia with amblyopia and contact lens (CL) intolerance in
      children. SETTING: Department of Ophthalmology, Masaryk University Hospital,
      Brno, Czech Republic. METHODS: This prospective comparative study comprised 27
      children with high myopic anisometropia and amblyopia. The mean age of the
      children was 5.4 years (range 4 to 7 years). Multizonal PRK (13 eyes) or LASEK
      (14 eyes) was performed in the more myopic eye under general anesthesia using the
      Nidek EC-5000 excimer laser. After surgery, the dominant eye was patched. The
      postoperative visual and refractive outcomes were analyzed; all children had a 2
      year follow-up. The 27 children (Group A) were compared with a control group of
      30 children (mean age 5.1 years) (Group B) in whom myopic anisometropia and
      amblyopia were treated conventionally by CLs and patching the dominant eye. The
      visual acuity and binocular vision outcomes in both groups were analyzed and
      compared. RESULTS: In Group A, the mean spherical equivalent refraction was -8.25
      diopters (D) +/- 2.37 (SD) (range -6.00 to -11.25 D) preoperatively and -1.61 +/-
      0.73 D (range +0.50 to -2.25 D) postoperatively. The mean best corrected visual
      acuity (BCVA) was 0.23 +/- 0.21 preoperatively and 0.78 +/- 0.19 at 2 years. In
      Group B, the mean BCVA was 0.16 +/- 0.19 at the start of CL correction and
      amblyopia therapy and improved to 0.42 +/- 0.15 after 2 years. The mean BCVA at
      the final examination was significantly better in Group A (P<.05). Binocular
      vision improvement expressed by the proportion of patients who gained fusion and
      stereopsis was better overall in Group A (78%) than in Group B (33%) (P<.05).
      There were no complications postoperatively. CONCLUSIONS: Photorefractive
      keratectomy and LASEK were effective and safe methods for correcting high myopic
      anisometropia and improving amblyopia in children aged 4 to 7 years who were CL
      intolerant. Visual acuity and binocular vision outcomes were better in children
      who received permanent surgical correction of anisometropia than in those who
      were treated conventionally by CLs.

PMID- 14967272
TI  - Completion rate of continuous curvilinear capsulorhexis in pediatric cataract
      surgery using different viscoelastic materials.
AB  - PURPOSE: To determine whether viscoelastic materials with a higher viscosity
      allow better control of the lens capsule, reducing the rate of incomplete
      continuous curvilinear capsulorhexis (CCC) during pediatric cataract surgery.
      SETTING: Department of Ophthalmology, University of California, San Francisco
      Medical Center, San Francisco, California, USA. METHODS: This retrospective study
      comprised 25 eyes of 18 children who had cataract surgery by 1 surgeon. The type
      of viscoelastic agent used for the CCC portion of the surgery was obtained from
      surgical dictations and nursing charts and information on complications during
      the CCC, from surgical dictations. The patient's age, type of cataract, and
      intraocular lens placement were also obtained. RESULTS: A CCC was successfully
      performed in 7 of 15 eyes (46.7%, mean age 7.6 years) using cohesive Healon
      (sodium hyaluronate 1%) or dispersive Viscoat (sodium hyaluronate 3%-chondroitin
      sulfate 4%) viscoelastic material and in 9 of 10 eyes (90%, mean age 6.4 years)
      using the high-viscosity viscoadaptive agent Healon 5 (sodium hyaluronate 2.3%)
      (chi square = 4.8900; P<.05). The unsuccessful CCCs in the Healon/Viscoat group
      were in 2 eyes with mature cataract, 1 eye with posterior polar cataract, 1 eye
      with posterior subcapsular cataract, and 4 eyes with lamellar cataract. The
      unsuccessful CCC in the Healon5 group was in 1 eye with mature cataract.
      CONCLUSION: The superviscous properties of Healon5 under low turbulence
      conditions appear to lead to a higher CCC completion rate in children.

PMID- 14967273
TI  - Cataract surgery in children with and without retinopathy of prematurity.
AB  - PURPOSE: To report the outcomes of cataract surgery in children born prematurely
      who had or did not have retinopathy of prematurity (ROP). SETTING: Seoul National
      University Hospital, Department of Ophthalmology, Seoul, Korea. METHODS:
      Retrospective studies were conducted by reviewing the charts of 26 eyes of 14
      premature infants with or without ROP that had cataract surgery. The patients'
      preoperative characteristics and postoperative visual outcomes were documented.
      Cataract surgery consisted of lensectomy, posterior capsulectomy, and anterior
      vitrectomy in patients younger than 2 years and primary posterior chamber
      intraocular lens (PC IOL) implantation or secondary PC IOL implantation in those
      2 years or older. Postoperative optical correction in those younger than 2 years
      was by glasses or contact lenses. RESULTS: Eight eyes of 5 patients had acute
      ROP; 4 eyes had stage 3, 2 had stage 2, and 2 had stage 1. Three eyes had
      transconjunctival cryotherapy for treatment of threshold ROP. First-eye cataract
      surgery were performed in children from 0.2 to 5.5 years old (mean 1.5 years) and
      second-eye surgery, in children from 1.8 to 12.1 years old (mean 4.3 years).
      Twenty eyes had implantation of a PC IOL. In 1 patient with stage 3+ ROP, Rush
      (plus) type, both eyes had combined cataract and scleral buckle encircling
      surgery. The mean follow-up after the last surgery was 1.4 years (0.5 to 3.1
      years). At the last examination, the best corrected visual acuity was good
      fixation or better than 20/80 except in 2 eyes, 1 with esotropia and the other
      with a dense pupillary membrane. CONCLUSIONS: This is the first report of an
      encouraging surgical outcome for PC IOL implantation in premature infants with
      cataract regardless of the presence of ROP. However, if retinopathy is present
      and has progressed in the cataractous eye of a premature child, careful
      examination and timely surgical decisions are important.

PMID- 14967274
TI  - Cataract surgery in patients with Vogt-Koyanagi-Harada syndrome.
AB  - PURPOSE: To evaluate the outcomes of cataract surgery in patients with Vogt
      Koyanagi-Harada's (VKH) syndrome. SETTING: Medical Research Foundation, Sankara
      Nethralaya, Chennai, India. METHODS: Fifty-nine eyes of 39 patients with VKH
      syndrome who had cataract surgery between May 1985 and June 2001 were
      retrospectively analyzed. RESULTS: Extracapsular cataract extraction (ECCE) with
      intraocular lens (IOL) implantation was performed in 15 eyes and without IOL
      implantation in 31 eyes. Phacoemulsification with IOL implantation was performed
      in 13 eyes. Twenty-three eyes (38.9%) had mixed cataract (posterior subcapsular
      and posterior polar). Small pupils were managed by synechiolysis with an iris
      spatula (43 eyes) or iris hooks (8 eyes). Nine eyes were lost to follow-up and
      not included in the postoperative analysis. The mean postoperative follow-up was
      39.4 months (range 9 to 120 months). Visual acuity improved by 1 or more lines in
      40 eyes (80.0%). Subretinal gliosis and optic atrophy, sequelae of the syndrome,
      restricted improvement in vision in the remaining eyes. Posterior capsule
      opacification developed in 38 eyes (76.0%), of which 21 (42.0%) required a
      neodymium:YAG laser posterior capsulotomy. There were no significant differences
      in postoperative inflammation or syndrome reactivation between the types of
      surgery. CONCLUSIONS: The results show that cataract extraction in patients with
      VKH syndrome can be safely and successfully performed if there are good
      preoperative and postoperative control of inflammation, careful surgical
      planning, and meticulous surgical technique. The final visual outcome depends on
      the posterior segment complications of the syndrome.

PMID- 14967275
TI  - Binocular vision impairment after refractive surgery.
AB  - PURPOSE: To illustrate the need for an accurate preoperative orthoptic
      examination to prevent postoperative changes in binocular vision. SETTING:
      Department of Ophthalmology, University Hospital Antwerp, Edegem, Belgium.
      METHODS: Five patients presenting major subjective complaints after refractive
      surgery were analyzed. RESULTS: In 1 patient, a latent N IV palsy decompensated
      after laser in situ keratomileusis (LASIK) in the more myopic eye to achieve
      monovision. A second patient, operated on for N IV palsy 10 years earlier,
      presented a recurrence of the palsy after bilateral LASIK for myopia. The third
      patient complained of discomfort in binocular vision caused by aggravation of a
      preexisting intermittent esotropia that worsened after LASIK for hyperopia. The
      fourth patient complained of diplopia after LASIK in the highly anisometropic and
      exotropic eye. The fifth patient experienced a decrease in fusion and stereopsis
      at the time he became anisometropic after bilateral LASIK. CONCLUSIONS: Special
      care should be taken of patients who have a preoperative history of strabismus
      surgery, an overcorrection or undercorrection in 1 or both eyes, or anisometropia
      and of those who are unhappy with contact lenses. An orthoptic examination should
      be done with and without spectacle correction to detect underlying vertical
      phorias. Intended monovision should be examined initially using contact lenses.

PMID- 14967276
TI  - Outcomes of laser in situ keratomileusis in patients with pigment dispersion
      syndrome.
AB  - PURPOSE: To analyze the outcome of laser in situ keratomileusis (LASIK) in
      patients with pigment dispersion syndrome (PDS). SETTING: Outpatient ambulatory
      laser vision correction centers. METHODS: This noncomparative case series
      reviewed the medical records of 12 patients (22 eyes) who had clinical features
      consistent with PDS at the time of the initial preoperative refractive evaluation
      and had LASIK surgery. RESULTS: Twenty eyes (90.9%) of 11 patients had an
      uneventful course after LASIK and a good final uncorrected visual acuity (mean
      follow-up 26 months). One patient (2 eyes) with PDS and suspicion of glaucoma on
      topical beta-blocker therapy had delayed healing, fluctuations in vision, and a
      lengthy visual recovery. CONCLUSIONS: Corneal findings of PDS do not appear to
      affect the intraoperative or postoperative outcomes of LASIK. However, patients
      who have PDS in the context of glaucoma and therapy with an intraocular-pressure
      lowering agent may experience delayed healing and a less predictable visual
      outcome.

PMID- 14967277
TI  - Late postoperative opacification of MemoryLens hydrophilic acrylic intraocular
      lenses: case series and review.
AB  - PURPOSE: To report clinical and spectrographic analyses of 2 explanted
      hydrophilic acrylic intraocular lenses (IOLs). SETTING: John A. Moran Eye Center,
      Salt Lake City, Utah, USA, and Johannes Gutenberg-University, Department of
      Ophthalmology, Mainz, Germany. METHODS: We report 6 cases of opacification of
      MemoryLens IOLs (Ciba Vision) that occurred approximately 2 years after
      implantation. The anterior and posterior surfaces of the IOLs had a white,
      frosted appearance, and the IOLs' interior looked brown, similar to the
      appearance of a brunescent cataract. Two of the IOLs were explanted because of a
      significant decrease in visual acuity. The IOLs were sent for further
      clinicopathologic analysis including scanning electron microscopy and energy
      dispersive x-ray spectroscopy (EDX). RESULTS: Microscopic analysis revealed
      multiple, fine, granular deposits of various sizes on the surface of the lens
      optics. The EDX analysis showed the presence of calcium within the deposits.
      CONCLUSIONS: Our cases show that hydrophilic acrylic IOLs can opacify even years
      after implantation. Analysis of the explanted IOLs revealed calcification.

PMID- 14967278
TI  - Intraindividual comparison of epithelial defects during laser in situ
      keratomileusis using standard and zero-compression Hansatome microkeratome heads.
AB  - PURPOSE: To determine the difference between the standard and a modified (zero
      compression) Hansatome microkeratome head (Bausch & Lomb) in the incidence of
      epithelial defects. SETTING: Department of Ophthalmology, Johann Wolfgang Goethe
      University, Frankfurt am Main, Germany. METHODS: Ninety-three patients (186 eyes)
      with a mean age of 39.1 years +/- 9.5 (SD) having laser in situ keratomileusis
      (LASIK) in both eyes were enrolled in a prospective randomized study using
      intraindividual comparison. In 1 eye, the flaps were created with the Hansatome
      microkeratome using the standard Hansatome head and in the other eye, the flaps
      were created with a microkeratome head with a modified design (zero-compression
      head). Intraoperative evaluation of epithelial defects was done using a
      standardized protocol. Statistical evaluation was performed with McNemar and
      Bowker tests. RESULTS: Epithelial defects occurred in 21 eyes (22.6%) in which
      the standard head was used and in 2 eyes (2.1%) in which the zero-compression
      head was used. In the former group, 15 (16.1%) of the epithelial defects were
      larger than 1.5 mm(2); the remaining 6 (6.4%) were smaller than 1.5 mm(2). In the
      latter group, both epithelial defects were smaller than 1.5 mm(2); both patients
      also had an epithelial defect in the eye in which the standard Hansatome head was
      used. The difference between the 2 Hansatome heads in the incidence (P<.001,
      McNemar) and size (P<.001, Bowker) of the epithelial defects was statistically
      significant. CONCLUSIONS: The Hansatome microkeratome with a zero-compression
      head significantly reduced the occurrence of intraoperative epithelial defects.
      The change in the construction of the Hansatome head is a useful improvement in
      LASIK technology.

PMID- 14967279
TI  - Decreased incidence of capsule complications and vitreous loss during
      phacoemulsification in eyes with pseudoexfoliation syndrome.
AB  - PURPOSE: To report a series of patients with pseudoexfoliation syndrome who had
      phacoemulsification without an increased incidence of intraoperative
      complications or late intraocular lens (IOL) dislocation. SETTING: Department of
      Ophthalmology, Kaiser Permanente, Denver, Colorado, USA. METHODS: Patients were
      prospectively recruited from a consecutive series of all cases of
      phacoemulsification performed by 1 surgeon. There were 67 eyes with
      pseudoexfoliation syndrome and 1670 eyes without pseudoexfoliation. The incidence
      of vitreous loss, capsule tears, and zonular dialysis was compared between the 2
      groups. RESULTS: The incidence of vitreous loss was 1.5% in eyes with
      pseudoexfoliation syndrome and 2.3% in eyes without pseudoexfoliation. The
      difference between the 2 groups was not statistically significant (chi square =
      0.203; P =.33). There were no cases of posterior capsule tears or zonular
      dialysis in pseudoexfoliation eyes without vitreous loss. No IOL dislocated over
      a mean follow-up of 54.1 months. CONCLUSION: Although caution is still advised,
      patients with pseudoexfoliation syndrome who have phacoemulsification can achieve
      results similar to patients without pseudoexfoliation.

PMID- 14967280
TI  - Relative afferent pupillary defect in patients with asymmetric cataracts.
AB  - PURPOSE: To prospectively investigate the incidence, associated factors, and
      prognostic significance of relative afferent pupillary defects (RAPDs) in eyes
      with less severe cataract than in contralateral eyes. SETTING: Department of
      Ophthalmology, Seoul Municipal Boramae Hospital, College of Medicine, Seoul
      National University, Seoul, Korea. METHODS: Forty patients with asymmetric
      cataract and a differences of 3 or more lines of Snellen visual acuity between
      eyes had detailed ophthalmic examinations including visual acuity, slitlamp
      evaluation, a swinging flashlight test before and after cataract surgery, and
      color vision assessment. RESULTS: Twenty-three of 40 patients (58%) had an RAPD
      (mean extent 0.39 log unit +/- 0.17 [SD]) in the eye with less severe cataract.
      The RAPD resolved or switched to the other eye after cataract extraction. All 5
      patients with a unilateral totally opaque lens had a contralateral RAPD,
      confirming the relationship between totally opaque cataracts and RAPDs. The
      difference in visual acuity between the 2 eyes did not differ between patients
      with RAPD and those without RAPD. There was no association between the presence
      of RAPD and postoperative visual acuity. CONCLUSIONS: More than half the patients
      with asymmetric cataract had an RAPD that resolved in the eye with less severe
      cataract after cataract extraction. All patients with a unilateral totally opaque
      lens had an RAPD. The presence of a preoperative RAPD was not related to
      postoperative visual acuity.

PMID- 14967281
TI  - Relationship of immediate intraocular pressure rise to phaco-tip ergonomics and
      energy dissipation.
AB  - PURPOSE: To evaluate the rise in intraocular pressure (IOP) after
      phacoemulsification using a straight microtip or a Kelman microtip and its
      relationship to phaco energy delivered to the eye. SETTING: Iladevi Cataract &
      IOL Research Center, Ahmedabad, India. METHODS: This prospective randomized study
      comprised 48 consecutive age- and sex-matched patients with senile cataract.
      Inclusion criteria included older than 45 years and presence of any type of
      cataract from grade I to III. The patients were divided into 2 groups: straight
      microtip and Kelman microtip. Each group comprised 13 men and 11 women. The mean
      age was 58.29 years +/- 6.46 (SD) in the straight microtip group and 60.05 +/-
      8.45 years in the Kelman microtip group. The IOP was measured preoperatively and
      postoperatively with a pneumotonometer and applanation tonometer. One surgeon
      performed all operations using a standardized surgical technique and topical
      anesthesia. The intraoperative mean phaco power and ultrasound (US) time were
      noted. The effective phaco time (EPT), percentage of IOP rise, and wound-site
      thermal injury (mild, moderate, or severe) were calculated. The correlation
      between the EPT and percentage of rise in IOP was evaluated using correlation
      coefficients and the paired t test. RESULTS: The mean preoperative IOP was 13.73
      +/- 2.89 mm Hg in the straight microtip group and 15.14 +/- 2.60 mm Hg in the
      Kelman microtip group. The mean US time was 239.4 +/- 1.61 seconds and 238.2 +/-
      1.48 seconds, respectively. The mean phaco power was 17.37% +/- 3.28% in the
      straight microtip group and 17.10% +/- 5.26% in the Kelman microtip group and the
      mean EPT, 39.06 +/- 2.28 seconds and 40.08 +/- 0.24 seconds, respectively (P
      =.412). The mean rise in IOP was 111.60% +/- 37.83% in the straight microtip
      group and 91.29% +/- 31.85% in the Kelman microtip group. The difference between
      groups was significant (P<.05). The correlation coefficient between the EPT and
      percentage of IOP rise was significant in both groups: 0.3823, straight microtip
      group (P<.05); 0.514, Kelman microtip group (P<.01). Wound-site thermal injury
      was noted in 3 patients in the straight microtip group and 1 patient in the
      Kelman microtip group. CONCLUSIONS: Although the amount of phaco energy
      dissipated in the eye was the same between the 2 groups, the percentage of IOP
      rise was greater with the straight microtip. The rise in IOP was correlated with
      the dissipated phaco energy.

PMID- 14967282
TI  - Phacoemulsification parameters: series 20000 Legacy Versus Legacy with AdvanTec
      software and NeoSoniX handpiece.
AB  - PURPOSE: To examine the differences in average phaco power and effective phaco
      time (EPT) and evaluate the clinical results with the standard Series 20000
      Legacy system (Alcon) and the Legacy with AdvanTec software and the NeoSoniX
      handpiece (Alcon). SETTING: Department of Ophthalmology, University Hospital,
      Hradec Kralove, Czech Republic. METHODS: The mean phaco power and EPT in 240 eyes
      of 240 consecutive patients having cataract surgery by a single surgeon using the
      standard Legacy 20000 system were retrospectively compared with results in 240
      eyes of 240 consecutive patients operated on by the same surgeon using the Legacy
      with AdvanTec software and the NeoSoniX handpiece. Statistical analysis was
      performed using the Kruskal-Wallis 1-way analysis of variance. All chi-square
      (chi(2)) values are approximations. RESULTS: The EPT and mean phaco power were
      less in the AdvanTec-NeoSoniX group than in the standard Legacy 20000 group in
      all cases. The mean EPT was 56.9 seconds +/- 29.5 (SD) in the standard Legacy
      20000 group and 4.2 +/- 3.8 seconds in the AdvanTec-NeoSoniX group. The mean
      phaco power was 19.2% +/- 6.2% and 5.1% +/- 2.5%, respectively. The difference
      between groups was statistically significant in EPT (age > or =90 years, chi(2) =
      4.5, P =.034; age <90 years, chi(2)>57, P<.00005) and in mean phaco power (chi(2)
      = 4.58 and P =.032 and chi(2)>44 and P<.00005, respectively). No trace of corneal
      striae or edema was observed in 92% eyes on the first postoperative day. The best
      corrected visual acuity was 20/25 or better in 60% of cases. CONCLUSIONS: The
      Legacy system with AdvanTec software and the NeoSoniX handpiece significantly
      reduced the mean EPT and phaco power. This low-power technology minimizes
      intraoperative damage to ocular structures and maximizes the level and rapidity
      of visual rehabilitation.

PMID- 14967283
TI  - Phacoemulsification with topical anesthesia performed by resident surgeons.
AB  - PURPOSE: To evaluate and compare the outcomes in phacoemulsification cases
      performed by resident surgeons using topical anesthesia or retrobulbar
      anesthesia. SETTING: Department of Ophthalmology, Emory University, Atlanta, and
      Department of Veterans Affairs Medical Center, Decatur, Georgia, USA. METHODS:
      This was a retrospective review of phacoemulsification cases performed by
      resident surgeons during 1 academic year. Variables analyzed included patient age
      and sex, preexisting conditions limiting final acuity, and type of anesthesia
      used. Outcomes measured included intraoperative and postoperative complications
      and final visual acuity. RESULTS: Of the 291 cases analyzed, 119 (40.9%) were
      retrobulbar and 172 (59.1%) were topical. Residents began using topical
      anesthesia after a brief introductory period with retrobulbar anesthesia.
      Vitreous loss occurred in 15 cases (5.1%), 8 retrobulbar (6.7%) and 7 topical
      (4.1%) (P =.42). Postoperative complications occurred in 30 cases (10.3%), 17
      topical (9.9%) and 13 retrobulbar (10.9%) (P =.85). Overall, 245 cases (84.2%)
      achieved a final best corrected visual acuity (BCVA) of 20/40 or better. When
      cases with preexisting conditions limiting final acuity were eliminated, 92.1%
      achieved a final BCVA of 20/40 or better. More topical cases (112, 65.1%) than
      retrobulbar cases (64, 53.8%) achieved a final BCVA of 20/25 or better (P =.06),
      and more topical cases (149, 86.6%) than retrobulbar cases (96, 80.7%) achieved a
      final BCVA of 20/40 or better (P =.19). CONCLUSION: Topical anesthesia is safe
      and efficacious for phacoemulsification performed by resident surgeons early in
      training after a brief introduction to phacoemulsification using retrobulbar
      anesthesia.

PMID- 14967284
TI  - Outcomes of sulcus implantation of Array multifocal intraocular lenses in second
      eye cataract surgery complicated by vitreous loss.
AB  - PURPOSE: To evaluate the outcomes of implantation of the Array((R)) multifocal
      intraocular lens (IOL) (model SA-40N, AMO) in the ciliary sulcus in second-eye
      cataract surgery complicated by vitreous loss. SETTING: Department of
      Ophthalmology, Arrowe Park Hospital, Wirral, United Kingdom. METHODS: This
      retrospective study comprised 15 patients who had complicated second-eye cataract
      surgery with loss of posterior capsule support leading to sulcus implantation of
      an Array multifocal IOL. The patients were recalled for assessment. Objective
      evaluation included uncorrected and corrected distance and near visual acuities,
      complications, and IOL centration. Subjective assessment was performed using a
      questionnaire that included the VF-14 index of visual function; the questions
      were related to satisfaction with vision, limitations from halos and glare, and
      the frequency of spectacle wear. RESULTS: Fourteen eyes (93%) had postoperative
      visual improvement. The best corrected distance acuity was 6/12 or better in 11
      eyes (73%). The best corrected near acuity was J2 or better in 12 eyes (80%). The
      IOL was well centered in 11 eyes (73%) and slightly decentered in 4 eyes (27%).
      Subjectively, patients indicated a high level of satisfaction with their distance
      and near vision. The VF-14 indicated high levels of visual function, with 73% of
      patients having a score higher than 90 (out of 100). Seventy-three percent of
      patients were not troubled by glare or halos, and 40% did not wear spectacles.
      CONCLUSION: Implantation of the Array multifocal IOL in the sulcus during
      complicated phacoemulsification led to good visual outcomes based on objective
      and subjective patient measures.

PMID- 14967285
TI  - Unsutured posterior chamber lens implantation in eyes requiring lens extraction
      at the time of pars plana vitrectomy with silicone oil tamponade.
AB  - PURPOSE: To describe a technique for the subsequent placement of an unsutured
      posterior chamber lens intraocular lens (PC IOL) in eyes requiring cataract or
      clear lens extraction at the time of pars plana vitrectomy (PPV) with silicone
      oil tamponade. SETTING: Department of Vitreoretinal Surgery, St. Thomas'
      Hospital, London, United Kingdom. METHODS: This retrospective review comprised 25
      patients who had phacoemulsification to allow an adequate intraoperative retinal
      view or adequate access to anterior retinal pathology. Anterior and posterior
      capsulorhexes were combined with an inferior radial capsulectomy to fashion a
      keyhole-shaped capsule. RESULTS: The mean follow-up was 15.9 months +/- 8.0 (SD)
      (range 3 to 34 months). Silicone oil was removed and IOLs were implanted in 15
      eyes (60.0%). Posterior chamber IOLs were implanted in 10 eyes (66.7% of those
      receiving an IOL), and anterior chamber AC IOLs were implanted in 5 eyes (33.3%).
      Nine of the 10 eyes receiving a PC IOL (60.0% of all IOLs) had uneventful
      surgery. In 1 eye, the PC IOL subluxated inferiorly. Two eyes developed pupil
      block that required further surgery. CONCLUSIONS: This technique allowed PC IOL
      implantation in 60% of eyes that received an IOL, showing that in selected
      patients who require simultaneous lens extraction and silicone oil tamponade, a
      keyhole-shaped capsulectomy provides for subsequent unsutured PC IOL insertion.
      The pupil block rate of 8% compares favorably with published rates. Refining the
      technique may allow it to be used in a greater proportion of eyes that would
      benefit from safe refractive correction.

PMID- 14967286
TI  - Clinical experience with 21-gauge manual microphacoemulsification using Sovereign
      WhiteStar Technology in eyes with dense cataract.
AB  - PURPOSE: To present a series of patients who had 21-gauge
      microphacoemulsification using Sovereign WhiteStar technology. SETTING: John A.
      Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah,
      USA. METHODS: Eighteen consecutive patients with cataracts judged to be 3+ or 4+
      on a 4-point scale were prospectively monitored for complications, energy used
      during phacoemulsification, and results 1 day and 3 months postoperatively.
      RESULTS: No complications occurred during nucleus removal. On a 4-point scale,
      the mean level of inflammation at 1 day was 0.9 +/- 0.5 (SD), with 13 patients
      having no corneal edema. Seven patients had an uncorrected visual acuity of 20/40
      or better on the first postoperative day. At 3 months, all corneas were clear,
      there was no sign of anterior chamber inflammation, and all patients had a best
      corrected visual acuity of 20/25 or better (best-case analysis). CONCLUSION:
      Results show that 21-gauge microphacoemulsification with Sovereign WhiteStar
      technology is safe and effective for removal of hard cataracts.

PMID- 14967287
TI  - Unexpected posterior capsule rupture with unfolding silicone plate-haptic lenses.
AB  - PURPOSE: To evaluate the incidence, management, and long-term outcomes of
      unexpected posterior capsule rupture during injection of a C11UB plate-haptic
      silicone intraocular lens (IOL) with the Passport II system (both Bausch & Lomb
      Surgical). SETTING: Tertiary referral center and teaching hospital. METHODS: This
      retrospective analysis comprised 24 cases of posterior capsule rupture during
      plate-haptic silicone IOL injection. RESULTS: Over 6 months, a C11UB IOL was
      injected after phacoemulsification in 3446 cases, from which 24 patients were
      drawn. Thus, the rate of posterior capsule rupture was 0.70%. The median
      preoperative best corrected visual acuity was 6/48 (range 6/12 to light
      perception). The median best spectacle-corrected acuity at the time of discharge
      or the last visit was 6/9 (range 6/4 to 6/24). Twenty patients had improved
      acuity, 2 lost 1 Snellen line, and 2 had unchanged acuity. There were no
      postoperative complications in 13 patients (54%). Three patients required further
      surgery. Twenty-one patients were discharged after a mean of 32 weeks +/- 22
      (SD); they required a mean of 5 +/- 4 visits. The remaining 3 continue to be
      followed because of their preoperative ocular comorbidity. CONCLUSIONS: Although
      no predisposing factor was identified, we believe the risk for posterior capsule
      rupture during IOL injection can be minimized by careful injection technique. In
      particular, if there is doubt about the integrity of the zonules, anterior
      capsule, or posterior capsule, a plate-haptic silicone IOL should not be
      injected. With the appropriate management, the final visual outcome was good.

PMID- 14967288
TI  - Laser in situ keratomileusis in human corneas: new organ culture model.
AB  - PURPOSE: To establish an in vitro model of laser in situ keratomileusis (LASIK)
      in human donor eyes and to test its validity in comparison with animal models.
      SETTING: Department of Anatomy, Friedrich-Alexander Unviersity, Erlangen,
      Germany. METHODS: Laser in situ keratomileusis was performed on 20 organ-cultured
      human corneal buttons. The excimer laser ablations ranged from 0 to 12.0
      diopters. The corneas were maintained in culture for up to 6 months and then
      evaluated with light microscopy and transmission electron microscopy. In
      addition, corneal sections were immunohistochemically stained for collagen type
      III, laminin, and fibronectin. The main outcome measures were the ultrastructural
      and immunohistochemical features of the stromal incision interface. RESULTS:
      Ultrastructural investigations in the peripheral cornea revealed a disarrangement
      of collagen fibers, indicating scar formation. These findings were not observed
      in the central area. Immunohistochemical staining for fibronectin and collagen
      type III was detected over the entire stromal incision interface, whereas laminin
      staining was related to the ingrowth of epithelial cells. CONCLUSIONS: The
      morphological changes after LASIK in an organ culture model can simulate the in
      vivo situation. Therefore, this model appears appropriate to use in further study
      of corneal wound-healing changes after LASIK.

PMID- 14967289
TI  - Analysis of cytoskeletal proteins in posterior capsule opacification after
      implantation of acrylic and hydrogel intraocular lenses.
AB  - PURPOSE: To analyze selected lens cytoskeletal proteins in posterior capsule
      opacification (PCO) 2 weeks after intraocular lens (IOL) implantation in rabbits.
      SETTING: Department of Ophthalmology, Dokkyo University School of Medicine,
      Tochigi, Japan. METHOD: Eight 10-week-old albino rabbits were prepared and
      anesthetized for phacoemulsification and aspiration of the crystalline lens and
      implantation of an acrylic or a hydrogel IOL. Two weeks postoperatively, the
      rabbits were killed and the IOLs removed for immunohistochemistry. Deparaffinized
      tissue sections were processed with antibodies against alpha-smooth muscle actin
      (alpha-SMA) and beta-crystallin to observe the types of PCO with the 2 IOL types.
      The proteins in the PCO tissue and the normal lens were homogenized, centrifuged,
      and analyzed using SDS-polyacrylamide gel electrophoresis (SDS-PAGE)
      densitometric analysis and Western immunoblotting for actin and vimentin.
      RESULTS: Immunohistochemistry demonstrated a fibroblastic cell type expressing
      alpha-SMA and partial regeneration of epithelial cells, resulting in a lenticular
      structure that stained irregularly for beta-crystallin. The immunoreactivity of
      fibroblast-like cells to beta-crystallin appeared weaker than that of the
      regenerated lenticular structure. SDS-PAGE showed variability in the content of
      cytoskeletal proteins in the insoluble fractions of the PCO. Degradation of the
      cytoskeletal components was greater with the acrylic IOL than with the hydrogel
      IOL. CONCLUSION: Cytoskeletal proteins expressed during the formation of PCO and
      IOL implantation may have potential as therapeutic target proteins to improve the
      biocompatibility of IOLs.

PMID- 14967290
TI  - Evaluation of preoperative and postoperative prophylactic regimens for prevention
      and treatment of diffuse lamellar keratitis.
AB  - PURPOSE: To investigate preoperative and postoperative prophylactic treatment
      with different pharmacological agents before flap cutting and exposure to a
      diffuse lamellar keratitis (DLK) causative agent. SETTING: Magill Research Center
      for Vision Correction, Storm Eye Institute, Medical University of South Carolina,
      Charleston, South Carolina, USA. METHODS: The study comprised 48 eyes of 24 Dutch
      belted rabbits. Three days before a corneal flap was cut and the corneal
      interface was exposed to Pseudomonas aeruginosa lipopolysaccharide endotoxin, a
      DLK causative agent, the eyes were randomly assigned to treatment with a mast
      cell stabilizer, a nonsteroidal antiinflammatory drug (NSAID), or a
      corticosteroid or left without treatment as controls. The treatment was
      maintained throughout the 1-week follow-up. Slitlamp examinations and photographs
      were performed at 1, 3, 5, and 7 days; DLK was graded by a masked observer from 0
      (no DLK) to IV. Corneal interface scrapings were performed in selected eyes on
      day 7. RESULTS: At the end of the follow-up, 36 eyes were available for
      evaluation. At 1 week, 100% of the control eyes and the eyes treated with the
      mast-cell stabilizer developed DLK; in the NSAID-treated and corticosteroid
      treated eyes, the DLK rate was 86% and 70%, respectively. At 1 day, the severity
      of DLK was significantly lower in eyes treated with the mast-cell stabilizer
      (0.44) and at 7 days, it was significantly lower in corticosteroid-treated eyes
      (0.3) than in the control group (1.5 and 1.4, respectively) (P<.05, Wilcoxon
      test). Corneal interface scraping from an eye with grade III DLK showed numerous
      inflammatory cells. CONCLUSIONS: Preoperative and postoperative treatment with
      corticosteroids significantly reduced the severity of DLK compared to the
      untreated control eyes in this animal model. Treatment with a mast-cell
      stabilizer and an NSAID had less effect on the postoperative course of DLK.

PMID- 14967291
TI  - Intraocular lens optic capture.
AB  - A continuous curvilinear capsulorhexis (CCC) provides a tear-resistant opening
      that allows use of a technique of capturing the intraocular lens (IOL) optic
      through the capsulorhexis opening when the opening is at least 1.0 to 2.0 mm
      smaller than the optic diameter. The technique provides stability and long-term
      centration of the IOL and prevents vitreous from extending anterior to the IOL.
      This paper reviews the current variations of optic capture including (1) haptics
      in the sulcus and IOL optic capture through a CCC, (2) haptics in the sulcus and
      IOL optic capture through an anterior capsule opening and a posterior CCC (PCCC),
      (3) haptics in the capsular bag and IOL optic capture through a PCCC, (4) haptics
      in the capsular bag and IOL optic capture through an anterior CCC, (5) haptics in
      the sulcus and IOL capture through a capsular membrane opening, and (6) haptics
      posterior to the capsular bag and IOL capture through a capsular membrane
      opening.

PMID- 14967292
TI  - International Intraocular Lens & Implant Registry 2004.
AB  - This article is the sixth annual printing of the International Intraocular Lens &
      Implant Registry. A total of 1548 intraocular lenses (IOLs) and nonoptical
      implants from 33 manufacturers are availabe to surgeons in 2004.

PMID- 14967293
TI  - Intacs for early pellucid marginal degeneration.
AB  - A 42-year-old man had Intacs (Addition Technology Inc.) implantation for early
      pellucid marginal degeneration (PMD). Two Intacs segments (0.45 mm thickness)
      were inserted uneventfully in the fashion typically used for low myopia
      correction (nasal-temporal). Eleven months after the procedure, the uncorrected
      visual acuity was 20/200, compared with counting fingers preoperatively, while
      the best spectacle-corrected visual acuity improved to 20/25 from 20/50. Corneal
      topographic pattern also improved. Although the results are encouraging, concern
      still exists regarding the long-term effect of this approach for the management
      of patients with PMD.

PMID- 14967294
TI  - Iridoschisis and bilateral lens subluxation associated with periocular eczema.
AB  - We present a 53-year-old man with bilateral lens subluxation, unilateral
      iridoschisis, and a long-standing history of periocular eczema. Although a case
      of unilateral lens subluxation and ipsilateral iridoschisis has been described
      recently, the pathogenesis of this simultaneous occurrence remains unclear. Our
      case raises questions about the relationship among these clinical observations
      and suggests that these findings may exist as part of an unrecognized oculodermal
      syndrome.

PMID- 14967295
TI  - Keratoglobus and posterior subcapsular cataract: surgical considerations and in
      vivo microstructural analysis.
AB  - We report sporadic, bilateral keratoglobus associated with posterior subcapsular
      cataract in a 43-year-old man. Slitlamp biomicroscopy showed symmetric arcus
      senilis-like deposits, a polygonal appearance resembling crocodile shagreen, an
      unusual endothelial appearance, and posterior subcapsular cataract. Orbscan II
      pachymetry maps (Bausch & Lomb) demonstrated bilateral diffuse corneal thinning
      (359.53 microm +/- 21.15 [SD] in the right eye and 379.61 +/- 11.49 microm in the
      left eye). These thickness values were confirmed by ultrasound pachymetry. In
      vivo confocal microscopy showed multiple criss-crossing dark lines and no
      identifiable cellular elements within the stroma. There were mild to moderate,
      guttata-like endothelial changes surrounded by pleomorphic cells.
      Phacoemulsification was performed in the left eye after careful consideration of
      the presenting features and modification of the surgical technique. Minimal
      structural alteration was observed during microstructural analysis 7 months after
      surgery. The endothelial morphology postoperatively was similar to that at
      baseline.

PMID- 14967296
TI  - Management of a posteriorly dislocated endocapsular tension ring and a foldable
      acrylic intraocular lens.
AB  - We report a rare case of late spontaneous extension of a posterior capsule tear
      from lateral traction of an endocapsular ring, resulting in dislocation of the
      capsular tension ring and acrylic intraocular lens (IOL) into the vitreous
      cavity. A 3-port pars plana vitrectomy was performed to explant the prostheses;
      the eye was made pseudophakic by placement of a scleral-fixated posterior chamber
      IOL. The combined triple procedure was safe and effective.

PMID- 14967297
TI  - Intraocular lens exchange assisted by preoperative neodymium:YAG laser haptic
      fracture.
AB  - We present 3 cases of intraocular lens (IOL) exchange in which a neodymium:YAG
      (Nd:YAG) laser was used before surgery to fracture a haptic and make intraocular
      manipulations easier and safer. Strategic placement of the fracture facilitates
      maneuvering to explant the IOL segments. Delaying pupil dilation until after the
      Nd:YAG laser is used and prudent positioning of the patient's head minimize the
      risk that freed IOL segments will damage the cornea or subluxate posteriorly into
      the vitreous cavity. Neodymium:YAG laser IOL fracture before explantation/
      exchange is a viable combined procedure.

PMID- 14967298
TI  - Brown haze in an Allergan SI-40NB silicone intraocular lens.
AB  - We report a case of brown haze in an 83-year-old Japanese man with an Allergan
      silicone intraocular lens (IOL). The day after surgery, the IOL in the capsular
      bag was opaque. The patient subsequently had an IOL exchange. Microscopic
      examination of the extracted IOL showed numerous spheroid structures on the
      optic. Although the exact cause of this complication is unknown, water
      incorporated into the material may have had a role in the development of the
      sphere-like structures.

PMID- 14967299
TI  - Late traumatic dislocation of laser in situ keratomileusis flaps.
AB  - We present 2 patients with late traumatic laser in situ keratomileusis flap
      dislocation 8 months and 17 months after surgery. One patient had a sharp trauma
      that caused a partial laceration and the second patient had a blunt trauma that
      caused a dislocation of the flap. The corneas were examined with slitlamp
      microscopy, computed corneal topography, and confocal microscopy. One flap was
      repositioned surgically; the other was treated conservatively with an eye patch.
      The final visual outcomes were good and illustrate the benefit of immediate
      attention and flap repositioning.

PMID- 14967300
TI  - Recurrent interface infiltration with hypopyon after astigmatic laser in situ
      keratomileusis on a penetrating corneal graft.
AB  - A 56-year-old woman was referred with recurrent interface infiltration and
      hypopyon after astigmatic laser in situ keratomileusis (LASIK) on a corneal
      graft. Pseudomonas aeruginosa was isolated as the causative pathogen. Penetrating
      keratoplasty had been performed 2 years before refractive surgery. After the
      antibiotic medication was tapered, 3 recurrences of interface infiltration with
      hypopyon were observed. Penetrating rekeratoplasty was deemed appropriate.
      Histological examination of the explanted corneal graft revealed anterior stromal
      neutrophil infiltration. This case illustrates that microbial pathogens brought
      underneath the flap by LASIK can persist months later despite antimicrobial
      treatment.

PMID- 14967301
TI  - Phakic toric intraocular lens implantation after flap decentration in laser in
      situ keratomileusis.
AB  - We describe a patient with flap decentration after laser in situ keratomileusis
      (LASIK) and subsequent phakic toric intraocular lens (IOL) implantation. A 19
      year-old man with mixed astigmatism had LASIK in the left eye complicated by flap
      decentration. Laser ablation was abandoned and implantation of a phakic toric IOL
      was done. Ten months after IOL implantation, the uncorrected visual acuity in the
      left eye was 20/25 and best corrected visual acuity was 20/20 with +0.25 -0.50 x
      90. Simulated keratometry values were 44.30@150 and 42.00@60 before LASIK and
      45.00@150 and 41.90@60 after IOL implantation. Phakic toric IOL implantation may
      be adequate treatment for flap decentration after LASIK in cases of mixed
      astigmatism.

PMID- 14967302
TI  - Acremonium fungal infection in 4 patients after laser in situ keratomileusis.
AB  - We present 4 patients who had laser in situ keratomileusis and were referred to
      our clinic with a diagnosis of infectious keratitis. Laser in situ keratomileusis
      was performed in all cases in the same operating room by different surgeons
      between April and May 2002. A partial penetrating keratoplasty was performed in
      all patients to control the process. A study of the corneas demonstrated the
      presence of the fungus Acremonium in all cases. Rigid asepsis during the surgical
      procedure is important to prevent this serious complication.

PMID- 14967303
TI  - Nattrassia mangiferae keratitis after laser in situ keratomileusis.
AB  - A 32-year-old man had photophobia and blurred vision 2 weeks after uneventful
      laser in situ keratomileusis to correct myopia. He was treated with steroids for
      suspected diffuse lamellar keratitis, antiherpetics, and antibiotic eyedrops, but
      the condition worsened and the patient developed further blurred vision, an
      inflamed eye, and pain. When referred to us, the patient had an extensive corneal
      ulcer with hypopyon and mycelia were reported in scrapings of the ulcer bed.
      Nattrassia mangiferae (Hendersonula toruloidea) was cultured from the specimen.
      The patient was treated with antifungal agents and 2 penetrating keratoplasties.
      At the last examination, the uncorrected visual acuity was 20/200.

PMID- 14967304
TI  - Effect of eye patching on postoperative inflammation after cataract surgery.

PMID- 14967305
TI  - Inadvertent staining of the vitreous with trypan blue.

PMID- 14967306
TI  - Relaxing anterior capsulotomy for a decentered intraocular lens.

PMID- 14967307
TI  - Correlation between interleukin-15 and granzyme B expression and acute lung
      allograft rejection.
AB  - The levels of interleukin (IL)-15 and granzyme B mRNA expression have been
      correlated with acute rejection episodes of kidney and heart allografts. Thus,
      the purpose of this study was to determine whether a correlation exists between
      the expression of IL-15 and granzyme B and acute lung allograft rejection. Toward
      this, the levels of IL-15 and granzyme B mRNA expression were determined in
      bronchoalveolar lavage-derived alveolar macrophages and total cells,
      respectively, from lung transplant patients with stable lung allograft function
      and patients undergoing acute rejection episodes. The expression levels of IL-15
      mRNA was significantly higher in the patients undergoing acute rejection as
      compared to patients with stable lung function (P=0.02). The expression levels of
      granzyme B mRNA was also significantly higher in the patients undergoing acute
      rejection as compared to patients with stable lung function (P=0.005). The
      Receiver-Operating-Characteristic curve demonstrated that acute rejection can be
      predicted with a sensitivity of 94% and specificity of 67% with the use of a
      cutoff value of 3.1 fg of granzyme B mRNA per microgram of total RNA (or 71%
      sensitivity and 75% specificity of a cutoff value of 9.1 fg/microg). These data
      indicate that IL-15 secreted by activated alveolar macrophages and granzyme B
      secreted by activated CD8+ cytotoxic T lymphocytes play important roles in the
      process of acute lung allograft rejection.

PMID- 14967308
TI  - Only the light chain is sufficient for the serine protease function of the
      membrane bound form of factor I on a xeno-surface.
AB  - The cell membrane-bound forms of whole factor I (fI-PI), the light chain of the
      serine protease (SP) domain (SP-PI), and the light chain plus the COOH-terminal
      45 amino acid (AA) of the heavy chain (SP+45-PI) were constructed. Chinese
      hamster ovary (CHO) cells, expressing these molecules were established by
      transfection of cDNA and confirmed by flow cytometry. Amelioration of complement
      mediated cell lysis and complement fragment deposition on the cell surface by the
      transfectant molecules was tested in each CHO cell by means of a lactate
      dehydrogenase (LDH) assay and flow cytometry, respectively. A highly expressed fI
      PI blocked human complement-mediated cell lysis by approximately 84% of the
      cells. CHO cell transfectants with SP-PI also showed a clear inhibition in cell
      lysis by human serum, whereas CHO cell transfectants with SP+45-PI showed no
      inhibition. In addition, fI-PI and SP-PI, but not SP+45-PI, suppressed C5b-9
      deposition on CHO cell surface. These data indicate that the last 45 amino acid
      of the heavy chain, including a disulfide bridge area, did not participate in the
      serin protease function of factor I. The results suggest that SP-PI has potential
      for use in clinical xenotransplantation.

PMID- 14967309
TI  - Lympho-myeloid chimerism achieved by spleen graft of green fluorescent protein
      transgenic rat in a combined pancreas transplantation model (TI03-029).
AB  - BACKGROUND: Multilineage chimerism is a promising strategy to induce donor
      specific tolerance. Because the beneficial effect of splenic grafting on
      tolerance induction is well known, we studied long-term hematopoietic chimerism
      and the fate of donor-derived cells after allogenic pancreas/spleen
      transplantation. METHODS: Green fluorescent protein (GFP) transgenic (Tg) Wistar
      rats were donors and combined pancreas/spleen transplantation (PST) or pancreas
      transplantation (PT) alone was performed on recipient LEW rats. Graft survival
      was compared between these two groups and the fate of donor-derived GFP(+) cells
      was analyzed by flow cytometry. In this system, the donor-derived cells were
      clearly defined as having lymphocytic or granulocytic lineage by cell size. T
      cell subsets of GFP(+) and GFP(-) cells in long graft-surviving rats were also
      characterized. RESULTS: The survival period of the grafted pancreas in PST rats
      was significantly longer than that of PT rats (P<0.001). Three of seven PST rats
      survived >250 days. The chimeric level of donor-derived GFP(+) cells in the
      recipient peripheral blood was markedly higher in PST rats. In rats with long
      surviving grafts, overall peripheral blood chimerism was more than 5%, and both
      lymphocytes and granulocytes generated from the grafted spleen were stable. T
      cell subsets in the recipient LEW rats varied according to the type of cells.
      CD4(+)CD8(+) subsets decreased in the GFP(+) cells and CD4(-)CD8(+) subsets
      increased in the GFP(-) (LEW) cells. CONCLUSION: We confirmed the combination
      effect of the grafted spleen on pancreatic graft survival. Donor lymphocytic and
      granulocytic lineages were generated in the recipients with long-surviving graft.
      It suggested that multilineage chimerism was often induced by the spleen graft
      and protected the pancreatic graft against rejection for a long period.

PMID- 14967310
TI  - Long-lasting donor passenger leukocytes after hepatic and intestinal
      transplantation in rats.
AB  - BACKGROUND: Donor passenger leukocytes (DPLs) that migrate after organ
      transplantation stimulate the recipient immune system and normally cause
      rejection and graft vs. host reaction. However, DPLs also contribute to the
      unresponsiveness to the donor organ. The quantity and quality of these migrating
      cells are considered dependent on individual transplanted organs. We compared the
      DPLs of the liver, which might contain somatic stem cells, with those of
      intestinal grafts that have highly immunogenetic cells. To study DPLs over a long
      period, we used green fluorescent protein (GFP) transgenic (Tg) rats developed by
      us as donors. METHODS: We performed orthotopic liver transplantation (OLT) and
      small bowel transplantation (SBT) from GFP Tg rats to wild recipients. A short
      course of tacrolimus (0.64 mg/kg, intramuscularly) was used to prevent
      antigenicity of the GFP. The fate of the DPLs in the peripheral blood and the
      recipient bone marrow was monitored by flow cytometry. Using long-surviving
      recipients, the GFP(+) cells in the graft and various host immunologic organs
      were measured and characterized by immunohistochemical staining. RESULTS: In both
      groups, the numbers of the GFP(+) cells in the peripheral blood increased
      transiently and then gradually decreased to undetectable levels. While no GFP(+)
      cells were identified in the long-surviving-recipient bone marrow, there were a
      few GFP(+) cells in the graft liver, graft mesenteric lymph nodes and the
      recipient spleen. These cells showed major histocompatibility complex (MHC) class
      II antigen. There was no significant difference in the migration patterns of the
      GFP(+) cells in the OLT and SBT rats. CONCLUSIONS: In both the OLT and SBT
      groups, the DPLs migrated transiently in the recipient peripheral blood. A small
      numbers of MHC class II-positive DPLs were present at the graft site and in the
      host spleen, but not in the bone marrow. There were no significant differences in
      the migration patterns of the DPLs between the OLT and SBT rats over the long
      term.

PMID- 14967311
TI  - Peripheral tolerance in transgenic mice expressing class I MHC L(d) only on
      cardiac cells.
AB  - BACKGROUND: The fate of autoreactive T cells exposed to extrathymic self-antigen
      is examined in a double transgenic (DTG) mouse [(L(d+) cardiacx2C)F1], where
      cardiac myocytes alone express L(d) and T cells express an antigen receptor (2C
      TCR) against L(d). METHODS: Naive cardiac L(d+) single transgenic (STG) mice
      (before breeding with 2C) and DTG mice were examined for evidence of
      autoimmunity. The L(d+) STG hearts were then transplanted to syngeneic L(d-) wild
      type C57BL/6 to evaluate the heart's immunogenicity. L(d+) skin grafts were
      transplanted to non-transgenic B6, transgenic 2C, STG, and DTG mice. Phenotype
      analysis of peripheral 1B2+(identifies 2C T cells), CD4+, and CD8+ T cells was
      performed by FACS. In vitro MLC and CTL, with and without the addition of IL-2
      and suppressor cell assays, were evaluated. RESULTS: Neither STG nor DTG hearts
      developed any evidence of autoimmunity by histology. In contrast, B6 mice
      rejected the L(d+) STG heart in 17+/-9.7 days (P<0.01), while a syngeneic B6
      heart transplant was accepted indefinitely. Survival of L(d+) skin grafts was
      prolonged in both STG and DTG mice. FACS quantitation revealed that while there
      was no deletion of peripheral 2C cells in the DTG, these 2C T cells did have a
      significantly reduced proliferative and cytotoxic response to H-2L(d).
      Restoration of the proliferative and cytotoxic response of the DTG cells by the
      addition of IL-2 was consistent with a state of anergy. CONCLUSIONS: These
      findings suggest that the expression of extrathymic class I MHC expression alone
      did not trigger autoimmune reactions but that the T cells can be rendered anergic
      to the specific 'self' antigen.

PMID- 14967312
TI  - Significant changes in the alloantibody after lung transplantation in the
      cyclosporine treated rat model.
AB  - BACKGROUND: The diagnosis of acute rejection after organ transplantation is often
      complicated by other possibilities, such as infection. Despite many attempts to
      identify rejection episodes after transplantation, only the detection of the
      humoral anti-human leukocyte antigen antibody has been effective in measuring
      alloimmunization, especially detected with flow cytometry cross-match (FCXM). As
      an initial step towards gaining a better understanding of the correlation between
      humoral responses and graft rejection in an immunosuppressant recipient, we
      investigated responses of alloantibodies (allo-Abs) after lung transplantation
      (LTx) in a rat model treated with adequate or inadequate cyclosporine A (CsA)
      therapy. METHODS: Orthotopic LTx was performed using a major histocompatibility
      complex fully incompatible combination (Brown Norway to Lewis rat). CsA was given
      subcutaneously to recipients at an optimal or a sub-optimal dosage for 3 days
      after transplantation. A FCXM technique was used to determine the time-course of
      changes in titers of allo-Abs in serum. The allo-Ab deposition in the grafted
      lung was detected with an immunofluorescent staining method. RESULTS: Circulating
      IgM allo-Ab levels were significantly elevated on day 4 in both groups when
      histological findings revealed early stage of acute rejection. IgM levels in the
      sub-optimal dosage group were maximal and significantly higher than those in the
      optimal dosage group on day 4, and levels then decreased after day 8. IgG allo-Ab
      levels increased significantly on day 8 and continued to increase throughout the
      observation period. CONCLUSIONS: Our data suggest that the monitoring IgM allo
      Abs might be effective for identifying acute rejection in recipients with
      inadequate immunosuppression therapy.

PMID- 14967313
TI  - Additional evidence of acute anti-inflammatory effects of cyclosporin A in a
      murine model of pleurisy.
AB  - INTRODUCTION: It is well known that cyclosporin A (CsA) exhibits important anti
      inflammatory effects, besides its immunosuppressive activity. However, the
      mechanisms by which CsA exerts these effects remain unclear. OBJECTIVE: This
      study evaluated whether the acute administration of CsA significantly interfered
      in leukocyte migration, exudation, myeloperoxidase (MPO) and adenosine-deaminase
      activities and nitrate/nitrite levels, in a mouse model of pleurisy. MATERIALS
      AND METHODS: Pleurisy was induced by carrageenan (1%) treatment and the
      parameters were analyzed 4 and 48 h after. Groups of animals were previously
      treated with different doses of CsA and compared with non-treated groups.
      RESULTS: CsA (0.1-5 mg/kg, intraperitoneal, 1 h before pleurisy induction)
      inhibited neutrophil migration (P<0.05), but not the exudation that occurred 4 h
      after pleurisy induction. At this time, CsA (1 mg/kg, 1 h before) also decreased
      nitrate/nitrite levels and MPO activity (P<0.01). CsA (2 mg/kg, 0.5 h before) was
      also effective in decreasing mononuclear influx, exudation and nitrate/nitrite
      levels 48 h after onset of inflammation. CONCLUSIONS: These results indicate that
      the acute administration of CsA is able to reduce the two leukocyte populations
      that occur both at 4 and 48 h after pleurisy induction, late exudation (48 h),
      MPO activity (4 h) and nitrate/nitrite levels (4 and 48 h). Taken together, these
      findings indicate that CsA has acute anti-inflammatory effects in immunocompetent
      animals.

PMID- 14967314
TI  - Immunosuppression, eotaxin and the diagnostic changes in eosinophils that precede
      early acute heart allograft rejection.
AB  - Peripheral blood eosinophil counts (EOS) are undetectable in 40% blood samples
      sent for routine haematology at Papworth Hospital during the first 3 months after
      heart transplantation (HTx). Increases in EOS usually precede the development of
      allograft rejection by a median of 4 days. We compared the effects of cyclosporin
      (dose and total blood concentration), prednisolone (dose and both total and
      unbound plasma concentrations) and azathioprine, as well as plasma concentrations
      of the CCR-3 chemokines, eotaxin and RANTES, on changes in EOS in 47 consecutive
      HTx recipients, with a median follow-up of 90 (IQR 85-95) days. Multivariate
      analysis confirmed the independent association between both prednisolone dose
      (P<0.0001) and eotaxin (P<0.0001) and changes in EOS. The plasma eotaxin
      concentration was, in turn, most closely associated with the cyclosporin dose
      (P<0.001) and plasma prednisolone concentration (P=0.022). The blood cyclosporin
      concentration (P=0.028), EOS (P=0.012) and prednisolone dose (P=0.015) were all
      independently associated with the risk of treated acute rejection. When
      prednisolone pharmacokinetic parameters were substituted for the prednisolone
      dose in this multivariate model, only the pharmacokinetic parameter retained a
      significant association with the risk of rejection. Changes in EOS preceding
      cardiac allograft rejection are directly associated with plasma eotaxin
      concentrations and indirectly with prednisolone dosage. Cyclosporin may also
      indirectly influence these changes by inhibiting eotaxin production. EOS,
      prednisolone dose and blood cyclosporin concentrations were independently
      associated with the risk of acute rejection. The total and unbound fractions of
      prednisolone in plasma appear to be even more closely related to rejection but
      are difficult to measure. Monitoring EOS, as a surrogate measure of prednisolone
      immunosuppression, may be more cost-effective for controlling rejection than
      conventional cyclosporin monitoring in the first 6 weeks after HTx.

PMID- 14967315
TI  - Donor non-specific IFN-gamma production by primed alloreactive cells as a
      potential screening test to predict the alloimmune response.
AB  - In order to devise an in vitro experimental system that predicts the in vivo
      generation of T lymphocytes capable of initiating the rejection process and
      thereby to individualize the immunosuppressive strategy in a rational way, we
      studied the in vitro strength of alloresponses to non-specific donors as a
      surrogate tool to identify patients with heightened alloimmunity. We measured
      interferon gamma (IFN-gamma) produced by primed alloactivated peripheral blood
      lymphocytes (p-allo-PBL) against third party stimulator PBLs in four groups by
      the enzyme linked immunospot (Elispot) assay: 16 with excellent renal transplant
      function (group 1); nine with chronic rejection (group 2); 11 allo-sensitized
      (PRA>60%) by graft loss on dialysis (group 3) and 36 normal controls (group 4).
      The Elispot assay was performed using 10(6) irradiated stimulator PBLs and 10(5)
      responder PBLs for 24 and 48 h. Each responder was challenged by 2-4 independent
      stimulators. RESULTS: At 24 h, mean+/-S.D. and 95% confidence intervals (CI) of
      spots/10(5) responder cells were 12.8+/-8.7 (10-15.5); 57.8+/-116 (11.9-103.7);
      77.5+/-91.3 (39.8-115.2); and 20.7+/-17.9 (17.4-24.1) in groups 1-4,
      respectively. P<0.01 between groups 1 or 4 vs. 2 or 3. An arbitrary spot level of
      >or=30 has positive and negative predictive values of 58% and 95%, respectively,
      sensitivity of 94% and specificity of 65% to identify patients with enhanced
      immunity. CONCLUSION: Chronic allogeneic stimulation is associated with enhanced
      p-allo-PBL. IFN-gamma producing frequencies against third party stimulators.
      Significant variation in IFN-gamma spots produced by p-allo-PBL may be useful to
      choose less allogeneic donors. Diminished p-allo-PBL alloresponse to third party
      stimulators may predict transplant patients with decreased alloresponses who may
      benefit from lesser immunosuppressive drugs.

PMID- 14967316
TI  - Anti-HLA antibodies in heart transplantation.
AB  - We have analyzed the relationship between the development of transplant-related
      coronary artery disease (TRCAD) and the following potential risk factors: (a).
      number of HLA mismatches between recipient and donor; (b). production of anti-HLA
      antibodies; (c). growth of lymphocytes infiltrating the graft; and (d). frequency
      of biopsy proven episodes of acute rejection. The study population consisted of
      285 adult heart allograft recipients who were monitored over a period of two
      years or more. The results demonstrate a significant correlation between TRCAD,
      generation of anti-HLA class II antibodies and potential of lymphocytes
      infiltrating the graft to proliferate ex-vivo in medium containing IL-2. Humoral
      and cellular immune responses to HLA-DR antigens expressed by the graft seem to
      underlie the development of TRCAD.

PMID- 14967318
TI  - Another milestone.

PMID- 14967317
TI  - Panel reactive antibody positivity and associated HLA antibodies in Turkish renal
      transplant candidates.
AB  - Pre- and post-renal transplantation panel reactive antibody (PRA) screening is
      associated with increased incidence of hyperacute or acute graft rejection and
      graft loss. This study was designed to find any relationship PRA sensitization
      and associated human leukocyte antigen (HLA)-specific antibodies in Turkish renal
      transplant candidates. We included 340 patients who were in the renal
      transplantation waiting list in the study. We determined PRA sensitization ratio
      and the associated anti-HLA IgG antibody distribution of the patient group. The
      PRA testing was currently performed and levels above 30% were accepted to be
      positive. The PRA class I positivity was determined in 24 (7%) and class II in 34
      (10%) of the patients. The most frequent HLA antibodies for class I were B56, A2,
      A34, A1, A23, A24 and B61; and for class II were DR11, DR14, DQ7, DR10, DQ5, DR1
      and DR7, respectively. From these, the increase of the numbers of anti-HLA class
      II antibodies was significantly correlated with the increase of PRA sensitization
      ratio. In conclusion, the identification of the associated HLA-specific
      antibodies and correlation with the Turkish population HLA antigen distribution
      will identify the high-risk patients who are candidates for transplantation.

PMID- 14967319
TI  - Restoring the joint line in revision TKA: does it matter?
AB  - The importance of joint line restoration in revision TKA is much debated today.
      This review paper gives an overview of the reasons why joint line elevation
      occurs so frequently in contemporary revision TKAs, what the theoretical and
      clinical consequences are of an elevated joint line and how it can be avoided.

PMID- 14967320
TI  - The 'Delhi active test' for detection of anterior cruciate ligament tears.
AB  - All the described tests for the detection of anterior cruciate ligament (ACL)
      tear are passive tests. For obese or muscular built patients these tests are
      cumbersome and often unsuitable. We describe for the first time a new method, the
      'Delhi active test', by which a torn ACL can be detected irrespective of the size
      or build of the patient. The results of this test are reproducible and the
      diagnostic accuracy is comparable with other tests. We suggest that the 'Delhi
      active test' be used as one of the routine clinical methods to detect the torn
      ACL.

PMID- 14967321
TI  - 10-16 year results of Leeds-Keio anterior cruciate ligament reconstruction.
AB  - Following initial enthusiasm in the late 1980s, the use of artificial ligament
      substitutes for anterior cruciate ligament (ACL) reconstruction has declined.
      However, the disadvantages of donor site morbidity for autologous graft and
      concerns about cross-infection from allogenic material have resulted in a
      maintained interest in prosthetic ligament substitutes. This study presents the
      outcome of ACL substitution using the Leeds-Keio (LK) polyester ligament at a
      mean of 13.3 years (range 10-16 years). Outcome was assessed using the
      International Knee Documentation Committee score, the Lysholm knee score, Tegner
      activity scale and American Knee Society Score and laxity by clinical examination
      and the Stryker Knee Laxity Tester. Standardized radiographs were taken to assess
      for evidence of degenerative change. The objective scoring tests showed that all
      patients experienced some degree of symptoms from their knee but functional
      impairment varied widely. Of the group, 28% were known to have ruptured their LK
      ligament and 56% had increased laxity compared with their opposite knee but no
      correlation could be shown between rupture, increased laxity and poor function.
      Of particular concern, all post-operative knees had radiographic signs of
      degenerative change compared with a rate of 39% in the contralateral knees.

PMID- 14967322
TI  - Comparison of expected vs. actual tunnel position in anterior cruciate ligament
      reconstruction.
AB  - In a prospective blinded non-randomised cohort study, 32 patients were assessed
      following anterior cruciate ligament reconstruction using autograft middle-third
      bone-patellar tendon-bone, over a period of 10 months. Two experienced surgeons
      performed the procedures, one using an arthroscopically assisted technique (16
      patients) and the other by mini-arthrotomy (16 patients). A comparison was made
      between the positions of the tunnels as perceived by the surgeon intra
      operatively with the actual position as shown on the post-operative X-ray. An
      independent blinded observer made the latter assessment. Actual vs. expected
      tunnel placement was analysed using the coefficient of correlation. The
      anteroposterior femoral tunnel position indicated perfect correlation (R(2)=1.00,
      P=0), and on the lateral view showed good correlation (R(2)=0.55, P=0.005).
      However, the tibial tunnel position anteroposteriorly showed poor correlation
      (R(2)=0.14, P=0.22), and on the lateral view no correlation (R(2)=0.07, P=0.36).
      The ideal tibial tunnel position is controversial, and in this study, two tibial
      tunnels were just anterior to the acceptable position and one was posterior.
      Altogether these three, and one other, were in very different positions to that
      expected by the surgeon. Surgeons may consider that before drilling the tibial
      tunnel, intra-operative confirmation of the guide-wire position would be helpful.

PMID- 14967323
TI  - A new method to determine graft angles after knee ligament reconstruction.
AB  - In posterior cruciate ligament (PCL) reconstruction, the acute angle of the graft
      at the tibial tunnel ('the killer curve') has been implicated as a cause of graft
      failure. Similar acute angles also occur at the entrance to the femoral tunnel.
      We describe a method to determine the true graft angle, based on measurements
      taken from two orthogonal radiographs in a cadaveric model, analysed using three
      dimensional geometry. The true angles for the tibial and femoral tunnels are
      presented for a variety of tunnel positions. The effect on these angles of knee
      flexion and extension is analysed. Resultant graft-tunnel forces at a constant
      ligament tension are described. Based on these results, drilling the femoral
      tunnel from outside-in and lateral placement of the tibial tunnel are
      theoretically advantageous.

PMID- 14967324
TI  - Valgus knee injuries: evaluation and documentation using a simple technique of
      stress radiography.
AB  - Clinical assessment of post traumatic ligament laxity is subjective. Stress
      radiographs provide an objective and permanent record of the laxity. We describe
      a simple method of stress radiography to help evaluate and to document valgus
      knee injuries. In this study we have correlated the X-ray findings with those at
      arthroscopy. No specialised equipment is required and radiation exposure to the
      patient and the surgeon is minimal. With the patient under general anaesthesia
      the injured and the normal knee are firmly bound together. A valgus stress is
      applied to both the knees simultaneously and a radiograph is taken. The opening
      of the medial joint space is measured as in the figure 1, i.e. the perpendicular
      distance between the tangent drawn to the subchondral bone of the femoral
      condyles, and the most medial point of the tibial plateau. The opening of the
      medial joint space provides a direct measure of valgus laxity. The ratio of the
      medial joint opening to the normal knee is calculated. A ratio of two or more is
      indicative of an associated anterior or posterior cruciate ligament rupture in
      addition to medial collateral ligament injury.

PMID- 14967325
TI  - Revision anterior cruciate ligament reconstruction: a midterm patient assessment.
AB  - Twenty patients who underwent revision anterior cruciate reconstruction were
      retrospectively reviewed. Before revision surgery all patients reported
      functional instability with daily and or sporting activities. The causes of
      primary graft failure have been identified. Four different types of graft were
      used for the revision reconstruction. A comprehensive knee analysis was used to
      assess the graft performance both subjectively and objectively at an arranged
      follow-up visit. In general our study shows that although there is residual
      antero-posterior laxity on clinical assessment and KT-1000 instrumentation after
      revision surgery, the majority of patients thought the results were subjectively
      good or excellent. The study highlights the well-recognised technical failures of
      primary anterior cruciate ligament reconstruction and confirms good subjective
      results. The poor correlation between the physical examination (objective) and
      the patient's perception (subjective) of the revision surgery is discussed.

PMID- 14967326
TI  - Sciatic nerve injury following hamstring harvest.
AB  - Injury to the sciatic nerve following harvesting of the medial hamstring tendons
      is a complication that has not been described. I report a unique case of sciatic
      nerve injury above the level of its bifurcation into its terminal branches
      following hamstring graft harvest for use in ACL reconstruction. The sciatic
      nerve anatomy and technique of graft harvest is briefly described.

PMID- 14967327
TI  - Conservative treatment of isolated posterior cruciate ligament injury in
      professional baseball players: a report of two cases.
AB  - Conservative treatment is currently recommended for most isolated posterior
      cruciate ligament (PCL) injuries in athletes. However, it is not known whether
      conservative treatment is applicable even in high performance athletes with
      isolated PCL injury. The results in two extremely high performance athletes,
      professional baseball players with isolated acute PCL injury treated
      conservatively are reported. A catcher and an out fielder, who were regular
      players, hurt their knees in baseball games. Magnetic resonance images of the
      knee detected complete PCL rupture. Following a carefully guided physical therapy
      program, a 3-week period of immobilization of the knee in full extension was
      achieved with a knee brace, while performing hard quadriceps muscle strengthening
      exercise, and then running exercise was started. Six to eight weeks after injury,
      they were able to return fully to their original sporting activity despite tibial
      posterior translation on posterior drawer test, and to sustain this activity over
      2 years. Switching of weight-bearing to non-weight-bearing in a deep knee flexion
      is considered to contribute to subjective instability in athletes with PCL
      deficiency. Probably because our cases, even though extremely high performance
      athletes were infrequently subjected to such a situation while playing baseball,
      they were able to return to their pre-injury level of athletic performance
      without severe subjective instability through conservative treatment.

PMID- 14967328
TI  - Clinical outcome and patient satisfaction in aseptic and septic revision total
      knee arthroplasty.
AB  - This study compares clinical outcome and patient satisfaction in 33 aseptic and
      15 septic revision total knee arthroplasties across a 30-130-month follow-up.
      Aseptic revisions included only knees in which the femoral, tibial and patellar
      components had been exchanged, and excluded knees in which only isolated patellar
      components had been revised or only the tibial insert exchanged. Septic revisions
      included only knees in which there had been successful revision for chronic
      infection without recurrence of infection for at least 2 years from the index
      revision. The evaluation included pain scores, knee scores, functional scores, SF
      12 functional surveys and radiographs of the knee. The results for the aseptic
      group were excellent in 26 (78.8%), good in 3 (9.0%), fair in 2 (6.1%) and poor
      in 2 (6.1%); those for the septic group were excellent in 5 (33.3%), good in 7
      (46.7%), fair in 2 (13.3%) and poor in 1 (6.7%). The overall results of septic
      revision were less satisfactory than for aseptic revision. Aseptic revisions
      achieved significantly better knee scores and ranges of motion than septic
      revisions, but their pain and functional scores were similar. Despite the
      difference in knee scores, 85% of the patients from both groups were equally
      satisfied with the results of treatment. There was no discernible radiographic
      difference between the two groups, including radiolucency.

PMID- 14967329
TI  - The use of chondrogide membrane in autologous chondrocyte implantation.
AB  - Autologous chondrocyte implantation is a new technique for the treatment of
      chondral defects in the knee. The exact procedure involved is continuously being
      developed with the ultimate aim of achieving hyaline cartilage regeneration. We
      present the outcome of our series of 31 patients, focussing on the use of the
      chondrogide membrane in the implantation process. Assessment is presented both in
      the form of arthroscopic appearance at approximately 1 year, and in the form of
      clinical outcome measures at 1 year and at 2 years after the second stage of the
      procedure. CONCLUSION: the use of chondrogide membrane in the fixation of cells
      during the implantation process is associated with satisfactory clinical outcome
      and does not appear to show evidence of hypertrophy at one-year arthroscopy, as
      compared to periosteum.

PMID- 14967330
TI  - Arthroscopic operations in joint tuberculosis.
AB  - We assessed the usefulness of arthroscopy in bone and joint tuberculosis (11
      knees, 1 elbow and 1 ankle). In all 11 patients with knee joint involvement the
      arthroscopic operation were successful with a significant improvement in the
      range of motion (P=0.007) and knee score (P=0.003). There were no cases of
      reactivation or recurrence during a follow-up period of 15-42 months. In
      contrast, in the two patients with ankle or elbow joint involvement and bone
      destruction, arthroscopy had to be converted to open operation. Minor trauma, a
      short hospitalization time and a short post-operative rehabilitation period
      combined with good cosmetic and clinical results favor the use of the
      arthroscopic technology in the surgical treatment of tuberculous arthritis of the
      knee.

PMID- 14967331
TI  - Heterotopic ossification in the knee following encephalitis: a case report with a
      10-year follow-up.
AB  - We present a case of heterotopic ossification in the bilateral knees of a 26-year
      old woman following viral encephalitis. After surgical excision, the patient was
      followed up for 10 years. Heterotopic ossification in knee joints associated with
      encephalitis has not been reported previously.

PMID- 14967332
TI  - Isolated rupture of the popliteus tendon in a professional soccer player.
AB  - We report an unusual case of an isolated intra-substance rupture of the popliteus
      tendon in a professional soccer player. The injury, sustained in a soccer tackle,
      was diagnosed on magnetic resonance imaging and subsequently confirmed on
      arthroscopic examination of the knee. The impinging proximal stump was debrided
      and the patient returned to playing competitive soccer within 6 weeks of surgery.

PMID- 14967336
TI  - Knowledge and attitudes of high school students regarding HIV/AIDS in Tunisia:
      does more knowledge lead to more positive attitudes?

PMID- 14967337
TI  - Reliability and validity of a fruit and vegetable screening measure for
      adolescents.
AB  - We developed and evaluated a brief measure of fruit and vegetable consumption for
      adolescents. The measure was reliable and significantly correlated with 3-day
      food record data. Correct classification rate (63%) and specificity (63%) were
      good. Sensitivity (33%) was lower. The measure is recommended, although
      improvements in classification are still needed.

PMID- 14967338
TI  - To screen or not to screen: prevalence of C. trachomatis among sexually active
      asymptomatic male adolescents attending health maintenance pediatric visits.
AB  - This study estimated the prevalence of Chlamydia trachomatis (CT) among sexually
      active, asymptomatic, multiethnic adolescent males attending preventive health
      maintenance visits at pediatric clinics within a large health maintenance
      organization. First-void urines of sexually active 14-18-year-old males were
      screened for CT. The CT infection rate was 4% (27/711), 95% CI = 2.5%, 5.5%.

PMID- 14967339
TI  - Navigating between cultures: the role of culture in youth violence.
AB  - The purpose of this paper is to review three cultural concepts (acculturation,
      ethnic identity, bicultural self-efficacy) and their relationship to the known
      risk and protective factors associated with youth violence. We conducted a review
      of the relevant literature that addresses these three cultural concepts and the
      relationship among culture, violent behavior, and associated cognition. The
      available literature suggests that ethnic identity and bicultural self-efficacy
      can be best thought of as protective factors, whereas acculturation can be a
      potential risk factor for youth violence. We examine the connection between these
      cultural concepts and the risk and protective factors described in the 2001
      Surgeon General's Report on Youth Violence, and present a summary table with
      cultural risk and protective factors for violence prevention. These concepts can
      assist physicians in identifying risk and protective factors for youth violence
      when working with multicultural adolescents and their families. Physicians are
      more effective at providing appropriate referrals if they are aware that
      navigating among different cultures influences adolescent behavior.

PMID- 14967340
TI  - Caught in the Crossfire: the effects of a peer-based intervention program for
      violently injured youth.
AB  - PURPOSE: To assess the effect of a hospital-based peer intervention program
      serving youth who have been hospitalized for violent injuries on participant
      involvement in the criminal justice system and violent reinjury and death after
      hospital discharge. METHODS: A total of 112 violently injured youth (ages 12-20
      years; 80% male; predominantly African-American [60%] and Latino [26%])
      hospitalized in Oakland, California participated in a retrospective case-control
      study. Clients were matched by age and injury severity. Treatment and control
      youth were followed for 6 months after their individual dates of injury. The
      outcome variables of rate of entry/reentry into the criminal justice system, rate
      of rehospitalization for violent injuries and rate of violence-related deaths
      were compared for treatment and control groups using an odds ratio analysis.
      RESULTS: Intervention youth were 70% less likely to be arrested for any offense
      (odds ratio [OR] = 0.257) and 60% less likely to have any criminal involvement
      (OR = 0.356) when compared with controls. No statistically significant
      differences were found for rates of reinjury or death. CONCLUSION: A peer-based
      program that intervenes immediately after, or very soon after, youth are
      violently injured can directly reduce at-risk youth involvement in the criminal
      justice system.

PMID- 14967341
TI  - Relationships of a brief measure of youth assets to health-promoting and risk
      behaviors.
AB  - PURPOSE: To test the utility of a brief measure of developmental assets for
      predicting risk and health-promoting behaviors. METHODS: Six "assets" questions
      were added to an existing school-based survey of health-related behaviors.
      "Asset" questions dealt with students' grades in school, their communication with
      parents about school, students' perceptions of their role in school decision
      making, students' participation in after-school activities and volunteering, and
      students' perceptions that they "matter" in their community. Participants were
      30,916 Vermont students in grades 8-12. The sample included approximately equal
      numbers of girls and boys. It was 92% white. Fifty-nine percent of students'
      mothers had completed at least some postsecondary education (according to student
      report). Data were analyzed by Chi-square techniques and logistic regression.
      RESULTS: Number of assets (0-6) was negatively related to students' engagement in
      each of seven risk behaviors, and positively related to three health-promoting
      behaviors. The effects of number of assets were in most cases independent of
      demographic variables. Among the six assets, academic success (grades in school)
      contributed the greatest effect for most of the outcome measures; however, each
      of the assets contributed significant independent effects to multiple risk- and
      health-behaviors. CONCLUSIONS: Students' assets, even if relatively few, may make
      important contributions to wellness, independent of other well-established
      demographic factors.

PMID- 14967342
TI  - The protective influence of spirituality and "Health-as-a-Value" against monthly
      substance use among adolescents varying in risk.
AB  - PURPOSE: To investigate the influence of two potentially protective factors,
      Health-as-a-Value and spirituality, on monthly alcohol, cigarette, and marijuana
      use in two multiethnic groups of adolescents varying in risk. METHODS: Three
      hundred-eighty-two students from continuation/alternative high school, a
      population considered at risk for drug use, participated in the study. The other
      sample of 260 students was drawn from a medical magnet high school, and is
      considered to be at lower risk. Similar surveys containing measures of
      spirituality, "Health-as-a-Value," and monthly substance use, were distributed.
      Logistic regression analyses were performed. RESULTS: The analyses revealed that
      spirituality was protective against monthly alcohol use and marijuana use in the
      lower risk sample. In the higher risk sample, spirituality was protective against
      all monthly use. "Health-as-a-Value" (HAV) was protective against monthly alcohol
      use in the low risk sample, and protective against all monthly use in the higher
      risk sample. Importantly, when both constructs were entered into the same model,
      spirituality and HAV were independently protective of all monthly use for the
      higher risk sample and of monthly alcohol use in the lower risk sample.
      CONCLUSIONS: These findings extend earlier work on protective factors. "Health-as
      a-Value" and spirituality may be protective against substance use in environments
      with different levels of use. Future studies should explore these findings in
      longitudinal analyses.

PMID- 14967343
TI  - Initiation of sexual intercourse among middle school adolescents: the influence
      of psychosocial factors.
AB  - PURPOSE: To explore potential psychosocial predictors for initiation of sexual
      intercourse among middle-school, inner-city youth, using longitudinal data from
      the Healthy and Alive! project. METHODS: We conducted hierarchical, logistic
      regression with adjustment for intraclass correlation over two sequential
      periods, including seventh and eighth grades (N = 3163), to assess the
      independent influence of psychosocial and demographic factors. Internally
      reliable scales to assess psychosocial influences were created, based on major
      theories of behavior. The sample was 52% female, 51% black, 30% Hispanic, 9%
      white, and 3% Asian. At baseline, 13% of girls and 39% of boys reported already
      having initiated sexual intercourse. RESULTS: Personal and perceived peer norms
      about refraining from sex were a strong and consistent protective factor. Alcohol
      and other drug use, poor academic performance, male gender, and black race were
      consistent risk factors. Self-efficacy showed a mixed effect: protective in the
      seventh grade but increasing risk in the eighth grade. Speaking a language other
      than English was a protective factor in seventh grade. Both psychosocial and
      demographic factors provided independent explanatory power. CONCLUSIONS:
      Psychosocial factors, particularly norms about having sex, influence initiation
      of sexual intercourse. These data suggest that programs to delay initiation of
      sexual intercourse should reinforce norms about refraining from sex.

PMID- 14967344
TI  - Primary and secondary sexual abstinence in high school students.
AB  - PURPOSE: To assess reasons for choosing not to have sexual intercourse among two
      groups: virgins (primary abstainers) and already sexually experienced youth
      (secondary abstainers). METHODS: 73,464 Minnesota ninth- and twelfth-grade
      adolescents completed the 1998 Minnesota Student Survey. Respondents identified
      reasons for abstinence from a checklist from which they could nominate all
      relevant items. Reasons for each group were analyzed using Chi-square with a
      conservative criterion value (p <.001) owing to large sample size. Logistic
      regression was used to examine the associations of gender, grade, and their
      interactions, with reasons for abstinence. RESULTS: Sixty-six percent reported
      never having had intercourse (primary abstainers). Among sexually experienced
      youth, 7.8% reported choosing not to have intercourse (secondary abstainers).
      Fear of pregnancy was the reason endorsed most often, more by girls than by boys
      (OR = 26 for primary abstainers, 6.9 for secondary abstainers). Fear of other
      adverse consequences, such as sexually transmitted infections, parental
      disapproval, or fear of getting caught, were generally selected by more girls
      than boys, and by more primary than secondary abstainers. Similarly, more girls
      and primary abstainers than boys or secondary abstainers generally selected
      statements reflecting normative beliefs on youth or their friends having
      intercourse. CONCLUSIONS: Fear of adverse consequences and normative beliefs
      about the appropriateness of having sexual intercourse were most frequently
      endorsed as important reasons by both groups of abstainers.

PMID- 14967345
TI  - New sex partner acquisition and sexually transmitted disease risk among
      adolescent females.
AB  - PURPOSE: To determine the association between new sex partner acquisition and
      incident STDs, to describe predictors of acquiring a new sex partner, and to
      compare new and established sex partnerships among adolescent females. METHODS:
      Interview data and biological specimens for STD testing were collected from a
      sample of 411 adolescent females (average age 17.3 years, 44% black and 42%
      Hispanic) enrolled in a longitudinal study. The relationship between having a new
      sex partner and incident STD infection was estimated with logistic regression.
      RESULTS: Acquisition of a new sex partner during the 12-month follow-up period
      was common (24%) and significantly associated with an incident STD infection (OR
      = 3.0, 95% CI = 1.6-5.7). Predictors of new partner acquisition were younger age,
      younger age at first intercourse, and alcohol or drug use before sex in past 30
      days. Being in a new partnership was significantly associated with greater
      uncertainty about the partners' STD history and recent sex with others.
      CONCLUSIONS: Being in a new sex partnership is an important predictor of incident
      STD infection. Awareness of this risk can help clinicians identify individuals
      who are more likely to get STDs and therefore target STD testing and appropriate
      prevention messages.

PMID- 14967346
TI  - Body piercing and high-risk behavior in adolescents.
AB  - PURPOSE: To evaluate the association of body piercing with sociodemographic
      factors, peer substance use, and high-risk behaviors. METHODS: Cross-sectional
      analysis using Wave II of the National Longitudinal Study of Adolescent Health
      (Add Health) Public Use Dataset, a nationally representative, school-based sample
      of 4337 adolescents, aged 13-18 years, surveyed in 1996. The major predictor
      variable was body piercing at locations other than the ears. The outcome
      variables were selected from five areas of high-risk behaviors including sexual
      intercourse, substance use (problem drinking, smoking, and marijuana use),
      violent behavior (fighting and inflicting injuries), antisocial behavior
      (truancy, shoplifting, and running away), and mood problems (depression, suicidal
      ideation and suicide attempts). The association between body piercing and peer
      substance use was also examined. RESULTS: Females (7.2% vs. 1.5%) and older
      adolescents were more likely to report piercing (all p's <.01) In linear
      regression analysis, controlling for sociodemographic factors, body piercing was
      significantly associated with higher levels of peer substance use (beta = 1.40
      [99% CI.57-2.23]). In logistic regression analyses, controlling for
      sociodemographic factors, piercing was associated with sexual intercourse (OR =
      4.5 [99% CI 2.1-10.0]), smoking (3.1 [1.6-5.9]), marijuana use (3.0 [1.6-5.9]),
      truancy (2.6 [1.3-5.3]), running away from home (3.0 [1.2-7.2]), suicidal
      ideation (2.5 [1.2-4.9]), and suicide attempts (3.0 [1.2-7.5]). CONCLUSIONS:
      Clinically, body piercing may serve as a marker for higher levels of peer
      substance use and potential problem behavior.

PMID- 14967347
TI  - Hostility among adolescents in Switzerland? multivariate relations between
      excessive media use and forms of violence.
AB  - PURPOSE: To determine what kind of violence-related behavior or opinion is
      directly related to excessive media use among adolescents in Switzerland.
      METHODS: A national representative sample of 4222 schoolchildren (7th- and 8th
      graders; mean age 13.9 years) answered questions on the frequency of television
      viewing, electronic game-playing, feeling unsafe at school, bullying others,
      hitting others, and fighting with others, as part of the Health Behaviour in
      School-Aged Children (HBSC) international collaborative study protocol. The Chi
      square tests and multiple logistic regression analyses were applied to high-risk
      groups of adolescents. RESULTS: For the total sample, all bivariate relationships
      between television-viewing/electronic game-playing and each violence-related
      variable are significant. In the multivariate comparison, physical violence among
      boys ceases to be significant. For girls, only television-viewing is linked to
      indirect violence. Against the hypothesis, females' electronic game-playing only
      had a bearing on hitting others. CONCLUSIONS: Experimental designs are needed
      that take into account gender, different forms of media, and violence to answer
      the question of whether excessive media use leads to violent behavior. With the
      exception of excessive electronic game-playing among girls, this study found that
      electronic media are not thought to lead directly to real-life violence but to
      hostility and indirect violence.

PMID- 14967348
TI  - Suicide, high-risk behaviors, and coping style in homeless adolescent males'
      adjustment.
AB  - PURPOSE: To evaluate the association among suicide behaviors, high-risk
      behaviors, coping style, and psychological adjustment (i.e., depressive
      symptomatology, internalizing and externalizing behavior problems) in homeless
      and non-homeless adolescent males (aged 16 to 19 years). METHODS: Data were
      obtained from 100 homeless youth accessing an emergency shelter (Ottawa, ON). The
      comparison group was comprised of 70 youth accessing local community drop-in
      centers that lived with their parent(s)/guardian(s) and had never stayed in a
      shelter. Data were analyzed using Chi-square, Student's t-tests, and regression
      statistics. RESULTS: Relative to non-homeless youth, homeless youth were more
      likely to report drug, alcohol, and tobacco use, legal problems, academic
      difficulties, and mental health problems. Homeless youth presented with a higher
      prevalence of suicidal ideation, past suicide attempts, depressive
      symptomatology, and internalizing and externalizing behavior problems.
      Disengagement coping was a predictor of suicidal ideation, past attempts,
      depressive symptoms and both internalizing and externalizing behavior problems in
      homeless youth. CONCLUSIONS: Relative to non-homeless youth, findings indicate
      that homeless youth reported greater use of a disengaging coping style and are at
      greater risk for high-risk behaviors, past suicide attempts, and clinically
      elevated levels of depressive symptoms and behavior problems.

PMID- 14967349
TI  - Betel nut chewing: the prevalence and the intergenerational effect of parental
      behavior on adolescent students.
AB  - PURPOSE: To explore the betel nut chewing prevalence among students, analyze the
      probability and the odds ratio of ex-chewers and current chewers, as well as the
      correlation between parental behavior characteristics and those of adolescents
      chewing betel nut. METHODS: A cross-sectional survey was designed and 10,288
      Taiwanese students answered the questionnaires in 2002. A structured
      questionnaire included information about betel nut chewing behavior among the
      adolescent students, sociodemographic data, and the betel nut chewing practice
      among parents or classmates. Samples were randomly chosen from each cluster of
      different types of schools in various areas. Three different grade levels of the
      first, second, and third grade (ages 16-18 years) were selected. Frequency
      distribution was used to analyze the prevalence among adolescent students, and
      Chi-square tests were used to compare the differences of betel nut chewing
      behavior among genders and the effect of parental behavior and socioeconomic
      factors. Logistic regression was used to analyze the odds ratio of the prevalence
      of adolescent students' betel nut chewing in the different types of schools and
      by gender. RESULTS: When the parents' marriage was not successful, or was of a
      lower social status, a higher incidence of adolescent betel nut chewing was
      observed. It was easy to experience betel nut chewing in adolescence if either
      parent chewed betel nut. The prevalence of betel nut chewing among male students
      was higher than female students and among vocational school students than general
      school students. The odds ratio of agricultural school students to general school
      students was highest of all the ex-chewers and current chewers from different
      types of schools. CONCLUSIONS: Betel nut chewing behavior is related to the
      effect of parental behavior on adolescent students. Apparently, it is indicated
      that there is a significant intergenerational effect of the parent's behavior on
      their children's behavior.

PMID- 14967350
TI  - Smoking and suicidality among adolescent psychiatric patients.
AB  - PURPOSE: To investigate the relationship between smoking and suicidality among
      adolescent psychiatric patients in Finland. METHODS: Data from 157 patients (aged
      12-17 years) admitted to inpatient psychiatric hospitalization between April 2001
      and July 2002 were collected. Logistic regression analyses were used to examine
      the association between regular daily smoking and suicidality. The data were
      adjusted for several sociodemographic and clinical characteristics. RESULTS: The
      results showed over four-fold risk for definite and/or life-threatening suicide
      attempts among smoking adolescents in inpatient psychiatric facility compared
      with nonsmoking ones (OR 4.33, 95% CI 1.23-15.20). Also, the smoking adolescents
      had three times greater risk for occasional (OR 3.32, 95% CI 1.09-10.10) or
      frequent (OR 3.00, 95% CI 1.08-10.10) self-mutilation. Suicidality was more
      common among girls than boys and among those adolescents who suffered from
      depression. CONCLUSIONS: Among teens hospitalized for psychiatric illnesses,
      daily smoking was significantly related to suicide attempts and self-mutilation,
      even after controlling for several confounding factors, including psychiatric
      diagnosis.

PMID- 14967351
TI  - Ovarian function preservation in the cancer patient.
AB  - OBJECTIVE: To review the clinical modalities that are available to women
      receiving potentially sterilizing cancer therapy. DESIGN: The MEDLINE database
      was reviewed for all publications on medication, surgery, or assisted
      reproductive technology that could potentially preserve fertility in women who
      are receiving cancer therapy. CONCLUSION(S): There are many options available to
      a patient undergoing a treatment that will negatively impact her fertility. Many
      procedures and medical interventions have been proven successful both in terms of
      ovarian function and pregnancy rates. Other techniques have great potential but
      do not have long-term clinical data. It is important that the patient's primary
      care physician understand the methods available to preserve fertility in cancer
      patients and communicate this information to the patient.

PMID- 14967352
TI  - Why do couples discontinue in vitro fertilization treatment? A cohort study.
AB  - OBJECTIVE: To investigate reasons for discontinuation of IVF treatment. DESIGN:
      Prospective, cohort study. SETTING: Center for reproductive medicine at a large
      university hospital. PATIENT(S): The 450 couples of a cohort of 974 couples who
      started IVF treatment between January 1996 and December 1997 and did not achieve
      childbirth. INTERVENTION(S): The reasons for ceasing treatment were evaluated by
      scrutinizing the medical records for all couples (n = 288) who did not achieve
      live birth and who did not complete three stimulated IVF cycles. A questionnaire
      was sent to all patients for whom the reason for discontinuation was not obvious
      from the medical records (n = 211). MAIN OUTCOME MEASURE(S): Reasons for
      discontinuing IVF. RESULT(S): Of 450 couples not achieving live birth, 208
      completed their subsidized cycles, whereas 242 discontinued IVF. In 192 (79%) of
      the 242 cases, the reasons for ceasing treatment could be identified from records
      or questionnaires. The reason for discontinuation was psychological burden in
      26%, a poor prognosis in 25%, spontaneous pregnancy in 19%, physical burden in
      6%, serious disease in 2%, and other reasons in 7%. CONCLUSION(S): An
      unexpectedly high percentage of couples who performed IVF discontinued the
      treatment before the three cycles that were offered to a majority of the couples.
      A majority of these discontinuations were due to psychological stress. This
      information is of importance when counseling patients during treatment.

PMID- 14967353
TI  - Reasons for dropout in an in vitro fertilization/intracytoplasmic sperm injection
      program.
AB  - OBJECTIVE: To gain more insight into psychological aspects of dropping out from
      IVF-ICSI. DESIGN: Prospective cohort study. SETTING: University hospital-based
      tertiary care fertility clinic. PATIENT(S): Women entering their first treatment
      cycle of IVF or ICSI. INTERVENTION(S): Standardized psychological questionnaires
      were administered before the start of the treatment and after treatment. MAIN
      OUTCOME MEASURE(S): Reasons for dropout, state and trait anxiety, depression, and
      marital and sexual satisfaction. RESULT(S): Baseline psychological factors and
      the probability of dropout after IVF-ICSI treatment were found to be associated
      in the group that stopped treatment for psychological reasons. Those who were
      denied further treatment by the medical team, the "actively censored" group, did
      not show pretreatment differences regarding psychological measures in comparison
      with those who continued treatment. After treatment, the group that was denied
      further treatment showed higher levels of anxiety and depression compared with
      those that continued. CONCLUSION(S): Dropout, being a well-known phenomenon in
      IVF-ICSI, is related to preexisting psychological factors in IVF-ICSI. Actively
      censored patients were psychologically well-adjusted before treatment, but this
      changed after censoring.

PMID- 14967354
TI  - Follow-up of infertile couples who dropped out of a specialist fertility clinic.
AB  - Lack of commitment to infertility investigations and treatment was not the reason
      for patient dropout.

PMID- 14967355
TI  - Impact of psychological factors on dropout rates in insured infertility patients.
AB  - Recent research supports the theory that psychological factors play a significant
      role in insured patients dropping out of IVF treatment before they receive all
      covered cycles.

PMID- 14967356
TI  - When and why does the dream die? Or does it?
AB  - A large percentage of patients discontinues infertility treatment despite a
      reasonable prognosis and benefits that cover the costs. Recognition of this
      problem and appropriate intervention may play a role in helping couples remain in
      treatment.

PMID- 14967357
TI  - Psychological aspects of discontinuation of in vitro fertilization treatment.
AB  - A considerable number of patients discontinue in vitro fertilization treatment
      because of psychological reasons.

PMID- 14967358
TI  - Psychological interference in in vitro fertilization treatment.
AB  - Because several studies indicate that psychological factors play a role in
      dropping out of IVF treatment, the question arises as to whether psychological
      interference is indicated.

PMID- 14967359
TI  - Should we try to understand the high rate of dropout from fertility treatment?
AB  - Failure to adhere to therapy is common in couples with fertility problems.
      Explaining why is difficult and worthy of further investigation without
      stigmatizing assumptions.

PMID- 14967360
TI  - The changing face of peer review at the National Institutes of Health.
AB  - OBJECTIVE: To discuss the new peer review system at the National Institutes of
      Health (NIH) and to present the process undertaken to accomplish these changes,
      with an emphasis on the reproductive sciences. DESIGN: A discussion of the many
      NIH committees and their composition and reports leading to the changes in peer
      review affecting the reproductive sciences. RESULT(S) AND CONCLUSION(S): The
      Center for Scientific Review (CSR), which reviews grants for all NIH Institutes,
      will initiate the Cellular, Molecular, and Integrative Reproduction, the
      Integrative and Clinical Endocrinology and Reproduction, and the Pregnancy and
      Neonatology study sections in February 2004. The National Institute of Child
      Health and Human Development (NICHD)'s Division of Scientific Review has the
      following subcommittees, which started review in July 2003: Pediatrics;
      Developmental Biology; Biobehavior and Behavior Sciences; Population Science;
      Obstetrics and Maternal-Fetal Biology; Reproduction, Andrology, and Gynecology;
      and Function, Integration, and Rehabilitation Science.

PMID- 14967361
TI  - Development of culture media for human assisted reproductive technology.
AB  - Contemporary culture systems in human assisted reproductive technologies meet the
      metabolic needs of preimplantation embryos by addressing energetic and amino acid
      requirements in a stage-specific manner. This approach significantly enhances
      viability compared with the historical use of simple salt solutions or complex
      somatic cell media.

PMID- 14967362
TI  - Treatment of endometriosis and chronic pelvic pain with letrozole and
      norethindrone acetate: a pilot study.
AB  - OBJECTIVE: To determine the role of an aromatase inhibitor, letrozole, in the
      treatment of reproductive-age women with endometriosis and associated chronic
      pelvic pain. DESIGN: Phase 2, open-label, nonrandomized proof-of-concept study.
      SETTING: Outpatient tertiary-care center. PATIENT(S): Ten patients with
      endometriosis, all previously treated both medically and surgically, with
      unsatisfactory results. INTERVENTION(S): Endometriosis was diagnosed by biopsy
      and scored from an initial diagnostic laparoscopy performed within 1 month before
      treatment was begun. Oral administration of letrozole (2.5 mg), the progestin
      norethindrone acetate (2.5 mg), calcium citrate (1,250 mg), and vitamin D (800
      IU) was done daily for 6 months. Within 1-2 months after completion of the
      treatment, a second-look laparoscopy was performed to score and biopsy
      endometriosis. MAIN OUTCOME MEASURE(S): Changes in American Society for
      Reproductive Medicine (ASRM) scores for endometriosis, pelvic pain assessed by
      visual analog scale, serum hormone levels (FSH, LH, E(2), and estrone [E(1)]),
      and bone density (DEXA scan). RESULT(S): No histologically demonstrable
      endometriosis was present in any patient during the second-look laparoscopy. ASRM
      and pelvic pain scores decreased significantly in response to treatment. Overall,
      no significant change in bone density was detected. Gonadotropin levels were not
      significantly altered by treatment, and although circulating E(2) and E(1) levels
      were reduced, the decrease was not statistically significant. CONCLUSION(S): The
      combination of letrozole and norethindrone acetate achieved marked reduction of
      laparoscopically visible and histologically confirmed endometriosis in all 10
      patients and significant pain relief in nine out of 10 patients who had not
      responded previously to currently available treatments. On this basis, letrozole
      should be a candidate for the medical management of endometriosis.

PMID- 14967363
TI  - Equivalence of the 3-month and 28-day formulations of triptorelin with regard to
      achievement and maintenance of medical castration in women with endometriosis.
AB  - OBJECTIVE: The present study aims at demonstrating the equivalence of the 28-day
      and 3-month formulations of triptorelin SR (sustained release) in terms of
      percentage of patients achieving castration levels of estradiol (<==50 pg/mL) 84
      days after treatment initiation. DESIGN: A phase II, prospective, randomized,
      multicenter, open study was conducted in two parallel groups of women with
      endometriosis. SETTING: Academic hospitals. PATIENT(S): Seventy-two women with
      endometriosis. were treated with a single intramuscular injection of 3-month
      triptorelin SR, and 74 patients were treated with one intramuscular injection of
      28-day triptorelin SR every 28 days for 3 months. INTERVENTION(S): As part of two
      parallel treatment groups, 72 women were given a single intramuscular injection
      of 3-month triptorelin SR, and 74 women were given one intramuscular injection of
      28-day triptorelin SR every 28 days for 3 months. MAIN OUTCOME MEASURE(S):
      Percentage of patients achieving castration levels of estradiol at the end of the
      treatment period. RESULT(S): Patients participated in the study until resumption
      of menses. Ninety-seven percent of patients given the 3-month formulation and 94%
      of those given the 28-day formulation were in a state of medical castration on
      day 84. The mean time to achieve castration was shorter for the 3-month
      formulation, and the duration of castration was significantly longer. The FSH and
      LH parameters were comparable, though not always identical. CONCLUSION(S): The
      pharmacodynamic effects of the Decapeptyl SR 3-month formulation are equivalent
      to those of the 28-day formulation. The 3-month formulation provides the added
      advantage of a longer maintenance of medical castration in women who have
      endometriosis.

PMID- 14967364
TI  - Peritoneal fluid concentrations of epithelial neutrophil-activating peptide-78
      correlate with the severity of endometriosis.
AB  - OBJECTIVE: To assess the release of epithelial neutrophil-activating peptide-78
      (ENA-78) into peritoneal fluid in women with and without endometriosis. DESIGN:
      Retrospective study. SETTING: Nagoya City University Hospital. PATIENT(S):
      Surgery was scheduled in the proliferative or secretory phase of the menstrual
      cycle for 59 women with (n = 35) and without (n = 24) endometriosis.
      INTERVENTION(S): Peritoneal fluid samples were obtained at laparotomy or
      laparoscopy. MAIN OUTCOME MEASURE(S): The ENA-78 concentrations in the peritoneal
      fluid were measured using enzyme-linked immunosorbent assay (ELISA). RESULT(S):
      The concentrations of ENA-78 in the peritoneal fluid were markedly elevated in
      the endometriosis patients as compared with the controls, especially in women
      with severe stage disease. CONCLUSION(S): We conclude that ENA-78 is an important
      factor that may contribute to the pathogenesis of endometriosis, possibly
      promoting neovascularization.

PMID- 14967365
TI  - Cumulative first live birth after elective cryopreservation of all embryos due to
      ovarian hyperresponsiveness.
AB  - OBJECTIVE: To estimate cumulative chance for first live birth after elective
      pronuclear stage cryopreservation of all embryos due to ovarian
      hyperresponsiveness. DESIGN: Retrospective analysis with longitudinal follow-up.
      SETTING: Academic hospital. PATIENT(S): Thirty subjects with elective
      cryopreservation of all embryos due to ovarian hyperresponsiveness.
      INTERVENTION(S): Elective cryopreservation of all embryos at the pronuclear stage
      (n = 30) and subsequent cryopreserved-thawed ET (n = 51). MAIN OUTCOME
      MEASURE(S): Cumulative chance for first live birth. RESULT(S): Cumulative chance
      for first live birth was 77% when analyzed by intention to treat and 82% by
      treatment with ET. Nearly 40% of live births were multiple. CONCLUSION(S):
      Cumulative first live birth increased with repetitive ET after elective
      pronuclear stage cryopreservation of all embryos due to ovarian
      hyperresponsiveness. Multiple births, however, were frequent. In the context of
      initial ET attempts in young women, transfer of no more than two cryopreserved
      thawed embryos is advised.

PMID- 14967366
TI  - Risk factors for adverse outcomes in spontaneous versus assisted conception twin
      pregnancies.
AB  - OBJECTIVE: To evaluate risk factors for adverse outcomes in spontaneous vs.
      assisted conception twin pregnancies. DESIGN: Historical cohort study. SETTING:
      Four academic tertiary medical centers. PATIENT(S): Women with twin pregnancies,
      including 2,143 spontaneous and 424 assisted conception; 2,492 nonreduced and 75
      reduced. INTERVENTION(S): None (observational). MAIN OUTCOME MEASURE(S):
      Preeclampsia, preterm premature rupture of membranes, birth <32 weeks and <30
      weeks, low birth weight, very low birth weight, and slowed midgestation fetal
      growth (<10th percentile between 20 and 28 weeks). RESULT(S): Among nonreduced
      pregnancies, assisted conception was not significantly associated with any
      adverse outcomes; among nulliparas, the risk for preeclampsia was increased
      regardless of method of conception; among spontaneous conceptions, the risks for
      preterm premature rupture of membranes, low birth weight, very low birth weight,
      and slowed midgestation fetal growth were increased. Among all pregnancies, fetal
      reduction increased risks for birth <32 weeks and <30 weeks, low birth weight,
      very low birth weight, and slowed midgestation fetal growth. Among nulliparas
      with assisted conceptions, fetal reduction increased the risks for birth <30
      weeks, very low birth weight, and slowed midgestation fetal growth.
      CONCLUSION(S): These findings indicate that in twin pregnancies, assisted
      conception is not a risk factor for adverse outcomes, but rather specific factors
      that are more common among these pregnancies, such as nulliparity and fetal
      reduction, increase risks.

PMID- 14967367
TI  - Transmyometrial oocyte retrieval and pregnancy rates.
AB  - OBJECTIVE: To determine whether transvaginal, ultrasound-guided oocyte retrieval
      performed through the myometrium has a negative impact on IVF pregnancy rates.
      DESIGN: Retrospective cohort study. SETTING: Academic hospital and research
      center. PATIENT(S): A total of 5,115 IVF cycles performed at the Brigham and
      Women's Hospital between 1998 and 2001 were evaluated. In 85 cycles (1.7%), the
      oocyte retrieval needle passed through the myometrium because of ovarian position
      during retrieval. Each of these cases was matched to a control cycle by age,
      attempt number, and date of retrieval. INTERVENTION(S): Transmyometrial oocyte
      retrieval. MAIN OUTCOME MEASURE(S): Pregnancy rates. RESULT(S): There were no
      statistically significant differences in pregnancy rates between cases and
      controls. Cases were more likely than controls to have underlying tubal disease
      and adhesions as the primary cause of infertility. The groups did not differ
      significantly in terms of age, attempt number, estradiol level, follicle number,
      days stimulated, ampules of gonadotropins administered, number of eggs, number of
      embryos, or quality of embryos. CONCLUSION(S): Transmyometrial oocyte retrieval
      is an uncommon event. Clinicians and patients can be reassured that
      transmyometrial oocyte retrieval does not seem to decrease IVF pregnancy rates;
      however, a larger study with greater power might reveal a statistically
      significant difference.

PMID- 14967368
TI  - Dynamic changes in microtubular cytoskeleton of human postmature oocytes revert
      after ooplasm transfer.
AB  - OBJECTIVE: Study of the influence of ooplasm transfer on the microtubule dynamics
      in human postmature oocytes. DESIGN: Prospective experimental study. SETTING:
      Academic hospital-based fertility center. MATERIALS(S): Human in vitro matured
      (IVM) oocytes (n = 65). Experimental groups: In set 1, sibling oocytes were
      processed either within 2-3 hours ("young"; n = 16) or at 12-14 hours after
      maturation ("presumably postmature," or PPM; n = 14). In set 2, young and PPM
      oocytes (n = 6 and 10, respectively) were assigned to be ooplasm donors and
      recipients, respectively. In set 3, PPM oocytes were used as ooplasm donors (n =
      2) and recipients (n = 4). Control groups: Metaphase II oocytes from
      superovulated golden hamsters in set 1; sibling oocytes of ooplasm donor young (n
      = 4) and PPM oocytes (n = 7) in set 2; and sibling PPM oocytes in set 3 (n = 2).
      INTERVENTION(S): Immunocytochemistry for alphatubulin with or without treatment
      with taxol (Paclitaxel, a microtubule-enhancing agent) in set 1; aspiration and
      microinjection of approximately 20 picolitres ooplasm from donor young and PPM
      oocytes into recipient PPM oocytes in sets 2 and 3, respectively. Taxol treatment
      and tubulin immunocytochemistry on ooplasm recipients and control young and PPM
      sibling oocytes. MAIN OUTCOME MEASURE(S): Morphology and pattern of the
      microtubules in the spindle and ooplasm as evaluated by confocal microscopy and
      three-dimensional image reconstructions. RESULT(S): In set 1, taxol-untreated
      young oocytes had normal spindle morphology and orientation to the oolemma with
      no microtubules in the ooplasm. Taxol-treated young oocytes revealed markedly
      broadened spindle poles and minimal or absent ooplasmic microtubules. Taxol
      untreated PPM oocytes had variable spindle morphology and a notable increase in
      cortical ooplasmic microtubules. Taxol treatment of PPM oocytes resulted in a
      marked increase in ooplasmic microtubules in addition to a broadening of spindle
      poles and formation of polar asters. In set 2, control young and PPM oocytes had
      the same findings as the corresponding oocytes in set 1. However, all ooplasm
      recipient PPM oocytes showed a striking diminution in ooplasmic microtubules,
      despite the taxol treatment, compared with their sibling PPM control oocytes in
      set 2 and PPM ooplasm-injected PPM oocytes in set 3. CONCLUSION(S): Postmature
      oocytes exhibit a dynamic increase in ooplasmic microtubules. However, these
      changes revert after transfer of ooplasm from young oocytes.

PMID- 14967369
TI  - Value of the serum estradiol level for preventing ovarian hyperstimulation
      syndrome: a retrospective case control study.
AB  - OBJECTIVE: To assess the value of different serum E(2) cut-off levels for
      predicting women at risk for ovarian hyperstimulation syndrome (OHSS). DESIGN:
      Retrospective case-control study of a cohort of women undergoing assisted
      reproduction treatment (ART) over 12 months. SETTING: Tertiary university
      hospital. PATIENT(S): The study group included women with OHSS who fulfilled the
      endocrine inclusion criteria (n = 40). The control group was a random sample (n =
      40) from the cohort of women undergoing ART. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): To evaluate the sensitivity and specificity of different serum E(2)
      cut-off levels on day 11 of ovarian stimulation in preventing the establishment
      of OHSS. RESULT(S): Three hundred ninety-nine cycles (IVF and intracytoplasmic
      sperm injection) were undertaken between June 2000 and May 2001. The study group
      (n = 40) was compared with the control group (n = 40) undergoing ART during the
      same period of time. On day 8 of ovarian stimulation, the mean (SD) E(2) level in
      the study group was 8,517(5.3) pmol/L (2,320 pg/mL), and in the control group it
      was 2,540 (2.6) pmol/L (691 pg/mL). On day 11 of stimulation the mean (SD) E(2)
      level was 15,662 (4.2) pmol/L (4,266 pg/mL) and 5,804 (4.5) pmol/L (1,581 pg/mL),
      respectively. Twenty-four (60%) women who developed OHSS had E(2)levels >6,000
      pmol/L (1,634 pg/mL) on day 8 and above 11,000 pmol/L (2,996 pg/mL) on day 11.
      Sixteen (40%) had E(2) levels <6,000 pmol/L (1,634 pg/mL) on day 8, but all had
      levels above 11,000 pmol/l (2,996 pg/mL) on day 11. CONCLUSION(S): A serum E(2)
      level of 12,315 pmol/L (3,354 pg/mL) on day 11 of ovarian stimulation gives a
      sensitivity and specificity of 85% for the detection of women at risk for OHSS.

PMID- 14967370
TI  - AZF microdeletions of the Y chromosome and in vitro fertilization outcome.
AB  - OBJECTIVE: To determine whether the presence of a Y microdeletion confers any
      adverse effects on in vitro fertilization or intracytoplasmic sperm injection
      (IVF/ICSI) outcome. DESIGN: Retrospective case-control study. SETTING: Academic
      infertility center. PATIENT(S): A total of 17 patients with Y microdeletions who
      attempted IVF/ICSI cycles at our center between March 1996 and March 2002 were
      studied. Study patients were analyzed in two groups: those who underwent
      testicular sperm extraction (TESE) and those for whom ejaculated sperm was used.
      INTERVENTION(S): The two patient study groups were matched to controls treated at
      the same time who had either nonobstructive severe oligozoospermia or azoospermia
      with normal Y chromosomes. Controls were matched for age of the female partner,
      sperm concentration, and number of embryos transferred. MAIN OUTCOME MEASURE(S):
      Fertilization and clinical pregnancy rates. RESULT(S): Sperm was only obtained
      from patients with azoospermic factor (AZF)c microdeletions (and from one patient
      with a partial AZFb microdeletion). A trend toward lower fertilization rates in
      patients with Y microdeletions was noted, which did not reach statistical
      significance. Clinical pregnancy rates per cycle and per transfer were similar to
      those for controls. CONCLUSION(S): Patients with AZFc microdeletions seem to have
      IVF/ICSI outcomes comparable to those of controls with normal Y chromosomes.

PMID- 14967371
TI  - Fertility after cancer: a prospective review of assisted reproductive outcome
      with banked semen specimens.
AB  - OBJECTIVE: To examine the outcome of assisted reproduction techniques (ART) using
      cryopreserved semen from patients with cancer. DESIGN: Prospective. SETTING:
      Therapeutic semen banking program at a tertiary healthcare center. PATIENT(S):
      Twenty-nine men with cancer who cryopreserved their sperm before treatment at our
      facility from 1982 to 2001 and withdrew their samples for assisted reproduction
      (IUI, IVF, or intracytoplasmic sperm injection [ICSI]). INTERVENTION(S): Sperm
      bank records were used to identify the patients. Information on fertility
      potential indices was obtained from medical records and through interviews. Of
      the 29 patients, 9 had testicular cancer, 12 had Hodgkin's disease, and 8 had
      other types of cancer. MAIN OUTCOME MEASURE(S): Pregnancy and live births.
      RESULT(S): A total of 87 ART cycles (42 IUI, 26 IVF, and 19 ICSI) was performed.
      Of those cycles, 18.3% resulted in pregnancy (7% IUI, 23% IVF, and 37% ICSI), and
      75% of the pregnancies resulted in a live birth (100% IUI, 83% IVF, and 57%
      ICSI). There was no significant difference in the outcomes when the results were
      stratified by type of ART and malignancy. None of the 11 infants who were born
      had congenital anomalies. CONCLUSION(S): Our findings emphasize the need for
      physicians to discuss the issue of semen cryopreservation with all men of
      reproductive age who have cancer before antineoplastic therapy is started.

PMID- 14967372
TI  - Novel association between sperm reactive oxygen species production, sperm
      morphological defects, and the sperm deformity index.
AB  - OBJECTIVE: To examine the relationship between sperm reactive oxygen species
      (ROS) production and sperm morphology in a group of infertile men and healthy
      fertile donors. DESIGN: A prospective clinical study. SETTING: Male infertility
      clinic, Glickman Urological Institute, The Cleveland Clinic Foundation,
      Cleveland, Ohio, and the Reproductive Medicine Unit, Liverpool Women's Hospital,
      United Kingdom PATIENT(S): Thirty-nine infertile men and 13 healthy fertile
      donors (control). INTERVENTION(S): Standard semen analysis, seminal leukocyte
      concentration, assessment of sperm morphology, and measurement of sperm ROS
      production. MAIN OUTCOME MEASURE(S): Levels of sperm ROS production, percentages
      of different sperm morphological abnormalities, and the sperm deformity index
      (SDI) scores. RESULT(S): A significant negative correlation was observed between
      sperm ROS production and the proportion of sperm with normal morphology and
      borderline morphology. Reactive oxygen species production was positively
      correlated with the proportion of sperm with amorphous heads, damaged acrosomes,
      midpiece defects, cytoplasmic droplets, tail defects, and SDI scores. Logistic
      regression analysis identified a two-variable model including SDI and percentage
      sperm motility, which correctly identified 84% of individuals with high seminal
      ROS and 85% of individuals with low seminal ROS. The model had an overall
      accuracy of 85%. CONCLUSION(S): The standard semen analysis to assess sperm
      motility, sperm morphology, and the SDI scores is a useful tool in identifying
      infertile men with high seminal ROS in infertility clinics where facilities for
      measuring levels of seminal ROS are not available.

PMID- 14967373
TI  - Nonobese women with polycystic ovary syndrome respond better than obese women to
      treatment with metformin.
AB  - OBJECTIVE: To determine the clinical, hormonal, and biochemical effects of
      metformin therapy in obese and nonobese patients with polycystic ovary syndrome
      (PCOS). DESIGN: Controlled clinical study. SETTING: Department of Gynecology of
      Federal University of Sao Paulo, Sao Paulo, Brazil. PATIENT(S): Twenty-nine
      patients with PCOS. INTERVENTION(S): Patients were treated with 500 mg of p.o.
      metformin t.i.d. for 6 months. MAIN OUTCOME MEASURE(S): Clinical data as well as
      serum concentrations of sex steroids, sex hormone-binding globulin (SHBG),
      gonadotropins, leptin, GH, lipids, insulin, and glucose levels were assessed
      before and after treatment. RESULT(S): In the metformin group of nonobese
      patients, the mean fasting serum insulin concentration decreased from a
      pretreatment value of 12.1 +/- 2.4 to 6.3 +/- 0.6 microU/mL after treatment, and
      the area under the curve of insulin decreased from 5,189.1 +/- 517.4 to 3,035.6
      +/- 208.9 microU/mL per minute. Also in the metformin group of nonobese patients,
      the mean basal serum total testosterone, free testosterone, and androstenedione
      concentrations decreased by 38%, 58%, and 30%, respectively. In the obese
      patients treated with metformin, only free testosterone showed a statistically
      significant decrease (1.7 +/- 0.2). CONCLUSION(S): Our data suggest that nonobese
      patients respond better than obese patients to a 1.5 g/day metformin regimen.

PMID- 14967374
TI  - Serum resistin levels in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To measure serum resistin levels in women with polycystic ovary
      syndrome (PCOS) and assess possible correlations of resistin to the hormonal and
      metabolic parameters of the syndrome. DESIGN: Clinical study. SETTING: University
      hospital. PATIENT(S): Ninety selected women were classified as follows: group I:
      35 anovulatory women with PCOS (body mass index [BMI] >25 kg/m(2)); group II: 35
      anovulatory women with PCOS (BMI <25 kg/m(2)); group III: 20 ovulating women
      (controls) without hyperandrogenemia (BMI <25 kg/m(2)); women of group III were
      volunteers. INTERVENTION(S): Blood samples were collected between the 3rd and the
      6th day of the menstrual cycle of the ovulating women, and between the 3rd and
      the 6th day of a spontaneous bleeding of the anovulatory women, at 9 a.m., after
      an overnight fast. MAIN OUTCOME MEASURE(S): Serum levels of FSH, LH, PRL, 17alpha
      hydroxyprogesterone, sex hormone-binding globulin, androgens, insulin, resistin,
      and glucose. RESULT(S): Resistin levels were found to be significantly increased
      in group I compared with those of group II and those of group III. No significant
      difference in resistin levels was found between groups II and III, despite
      significant differences in insulin levels and the glucose-to-insulin ratio.
      Multiple regression analysis showed that resistin levels do not correlate with
      any parameter independent of BMI. CONCLUSION(S): Based on the above findings, we
      presume that resistin is unlikely to be a major determining factor of PCOS
      associated insulin resistance and is not actively involved in the pathogenesis of
      the syndrome.

PMID- 14967375
TI  - Poor prognosis of recurrent aborters with either maternal or paternal reciprocal
      translocations.
AB  - OBJECTIVE: To determine whether the miscarriage rate in recurrent miscarriage
      patients with an abnormal karyotype, especially reciprocal translocations, in
      either partner is worse than without an abnormal karyotype. DESIGN:
      Retrospectively analyzed prospectively obtained database. SETTING: Nagoya City
      University Hospital. PATIENT(S): One thousand and two hundred eighty-four couples
      with a history of 2 or more (2 to 12) consecutive first-trimester miscarriages.
      INTERVENTION(S): Patients with antiphospholipid antibodies were treated with low
      dose aspirin and combined therapy. MAIN OUTCOME MEASURE(S): Subsequent
      miscarriages were compared for cases with and without an abnormal karyotype in
      either partner. A karyotype analysis was also conducted for each aborted
      conceptus and offspring of 95 pregnancies of 47 patients with reciprocal
      translocations. RESULT(S): Of the total of 1,284 couples, 58 (4.5%) had
      translocations, 11 being Robertsonian translocations. Eleven of the 18 cases
      (61.1%) where the husband had a reciprocal translocation suffered further
      miscarriage; this also was the case for 21 of the 29 cases (72.4%) where the
      wives had a reciprocal translocation. Those with reciprocal translocations in
      either partner miscarried significantly more frequently than those without an
      abnormal karyotype. Only one infant with an unbalanced translocation was found in
      34 cases of successful pregnancy following habitual abortion. CONCLUSION(S): The
      pregnancy prognosis with either maternal or paternal reciprocal translocations is
      poorer than without them. The presence of a reciprocal translocation is thus a
      risk factor in couples who have recurrent miscarriages.

PMID- 14967376
TI  - Single nucleotide polymorphisms in the promoter region of the interleukin-6 gene
      and the risk of recurrent pregnancy loss in Japanese women.
AB  - OBJECTIVE: To investigate the relationships between recurrent pregnancy loss and
      single nucleotide polymorphisms (-634C-->G and -174G-->C genotypes) in the
      promoter region of the interleukin (IL)-6 gene in the Japanese population.
      DESIGN: A case-control study. SETTING: Obstetrics and gynecology department of a
      university hospital. PATIENT(S): Cases were 76 women with recurrent pregnancy
      loss; controls were 93 fertile women. INTERVENTION(S): Determination of IL-6
      promoter gene polymorphisms performed by polymerase chain reaction and gel
      electrophoresis. MAIN OUTCOME MEASURE(S): Frequency and distribution of the
      promoter region of the IL-6 gene allele. RESULTS: There was a significant
      difference in the -634C-->G genotype frequency (CC vs. CG/GG) between women with
      recurrent pregnancy loss and controls. The risk of recurrent pregnancy loss was
      lower in the carriers of the G allele than in women with the wild type (CC) (odds
      ratio = 0.46; 95% confidence interval = 0.24-0.91). On the other hand, we did not
      detect any carrier of -174C among the 169 subjects. CONCLUSION(S): The results
      suggest that, in the Japanese population, women carrying the -634G allele of the
      IL-6 gene might have a decreased risk of recurrent pregnancy loss.

PMID- 14967377
TI  - Effects of alcohol consumption on female fertility during an 18-year period.
AB  - OBJECTIVE: To investigate the long-term effects of alcohol consumption on female
      fertility. DESIGN: Prospective study of a random sample of 7,393 women, selected
      from the 445,000 inhabitants of Stockholm County, Sweden, in 1969. Self-estimated
      alcohol consumption was obtained from postal questionnaires. Data on
      hospitalizations for pregnancy outcomes including infertility examinations were
      analyzed until 1987. SETTING: Healthy women in Stockholm County, Sweden.
      PATIENT(S): Seven thousand three hundred ninety-three women in the age range 18
      28 years. MAIN OUTCOME MEASURE(S): Rates of hospitalization for deliveries,
      miscarriages, legal abortions, extrauterine pregnancies, pelvic inflammatory
      disease, endometriosis, and infertility examinations were analyzed in relation to
      the intake of alcohol. RESULT(S): Two hundred fifty-two women underwent
      infertility examinations. High consumers had an increased risk for such
      examinations, as compared with moderate consumers: relative risk ratio (RR) =
      1.59 (95% confidence interval [CI]: 1.09-2.31); and low consumers had a decreased
      risk (RR = 0.64; CI: 0.46-0.90). Moreover, for both high and low consumers we
      observed a significantly lower number of first and second partus. Rates of
      miscarriage, extrauterine pregnancy, and pelvic inflammatory disease did not
      differ between high and low consumers of alcohol. CONCLUSION(S): High alcohol
      consumption was associated with increased risk of infertility examinations at
      hospitals and with lower numbers of first and second partus. It may be important
      for the female partner in an infertile couple to limit alcohol intake or to not
      drink at all.

PMID- 14967378
TI  - Negative lifestyle is associated with a significant reduction in fecundity.
AB  - OBJECTIVE: To evaluate the association patterns and quantify the effects of
      lifestyle on time to pregnancy (TTP). DESIGN: Observational study. SETTING:
      Teaching hospitals in Hull, United Kingdom. PATIENT(S): Two thousand and one
      hundred twelve consecutive pregnant women. INTERVENTION(S): A questionnaire
      inquiring about TTP, contraceptive use, pregnancy planning, previous
      subfertility/pregnancies, age, and lifestyle characteristics of either partner.
      MAIN OUTCOME MEASURE(S): We compared TTP, conception rates, and relative risk of
      subfecundity between subgroups with different lifestyle characteristics.
      RESULT(S): We found that TTP was significantly longer if the woman or partner
      smoked >15 cigarettes/day (P<.001 and.04, respectively), the partner consumed >20
      alcohol units/week (P<.001), the woman's body mass index was >25 kg/m(2)
      (P<.001), their coffee and/or tea intake was >6 cups/day (P=.04), or if they were
      socially deprived (P<.001). Each of these effects remained unchanged after
      adjusting for the potential confounders. The relative-risks of subfecundity with
      each of these variables ranged between 1.4 to 1.9 (1.4 to 3.6 after adjustment).
      The effects of coital frequency and recreational drug use were insignificant.
      Couples who had >4 negative lifestyle variables had a sevenfold longer TTP; their
      conception probabilities fell by 60%, and they were 7.3-fold more likely to be
      subfecund than those without negative variables. CONCLUSION(S): Lifestyle has a
      significant and cumulative impact on fecundity. Dose-dependent effects occur with
      smoking, alcohol, and tea/coffee consumption. Appropriate counseling could result
      in substantial reductions in the referrals for fertility investigations and
      treatments.

PMID- 14967379
TI  - Raloxifene therapy in postmenopausal women is associated with a significant
      reduction in the concentration of serum vascular endothelial growth factor.
AB  - OBJECTIVE: To determine whether raloxifene has an effect on serum vascular
      endothelial growth factor (VEGF) concentration in postmenopausal women. DESIGN: A
      randomized, placebo-controlled trial. SETTING: University-based obstetrics and
      gynecology unit. PATIENT(S): Fifty postmenopausal women who did not receive any
      hormone therapy in the 6 months preceding the study. INTERVENTION(S): The
      participants were randomly assigned on a one-to-one basis to receive either
      raloxifene (60 mg daily) or placebo for 36 weeks. MAIN OUTCOME MEASURE(S): Serum
      VEGF concentrations at baseline and at 12 weeks and 36 weeks after the
      commencement of intervention. RESULT(S): The serum VEGF concentrations in the
      raloxifene group were significantly reduced from 247 +/- 16 pg/mL at baseline to
      195 +/- 11 pg/mL at 36 weeks after starting raloxifene. The placebo group showed
      no significant change in the serum VEGF concentrations throughout the
      intervention period. CONCLUSION(S): Raloxifene therapy in postmenopausal women is
      associated with a significant reduction in serum VEGF concentration.

PMID- 14967380
TI  - Serum pattern of circulating free leptin, bound leptin, and soluble leptin
      receptor in the physiological menstrual cycle.
AB  - OBJECTIVE: To investigate the serum pattern of free leptin, bound leptin, and
      soluble leptin receptor throughout the physiological menstrual cycle. DESIGN:
      Prospective observational study. SETTING: Tertiary care center for gynecological
      endocrinology and reproductive medicine and a university research laboratory.
      PATIENT(S): Thirty regularly cycling volunteers (age, 29 +/- 4.2 years).
      INTERVENTION(S): Blood sampling was performed at different phases (early and mid
      follicular phase, preovulatory phase, and early and late luteal phase) of three
      consecutive menstrual cycles; each phase of the menstrual cycle was investigated
      twice. MAIN OUTCOME MEASURE(S): Free leptin, bound leptin, soluble leptin
      receptor, LH, E(2), P, vaginal ultrasound. RESULT(S): A peak of serum free leptin
      levels was found in the late luteal phase followed by a significant drop in the
      early follicular phase and again by a continuous increase up to the next luteal
      peak. There were no significant alterations in serum bound leptin and soluble
      leptin receptor levels. CONCLUSION(S): The present study shows that there are
      significant circacyclic fluctuations of free leptin levels with the highest
      concentrations in the late luteal phase and the lowest levels in the early
      follicular phase, which suggests that circulating free leptin is up-regulated by
      the C(21)-steroid (P). Circulating bound leptin and soluble leptin receptor are
      not altered by the cyclic hormone status. The significant rise of the leptin
      bioequivalent, free leptin, in the late luteal phase might be of importance for
      the luteal-follicular and the luteal-preimplantatory functional shift.

PMID- 14967381
TI  - Lifetime expression of stem cell markers in the uterine endometrium.
AB  - OBJECTIVE: To identify stem cells in uteri from the fetal to the postmenopausal
      period. DESIGN: Descriptive, controlled study. SETTING: Tertiary academic medical
      center. PATIENT(S): Forty archived uterine endometrial samples. INTERVENTION(S):
      Immunohistochemistry with c-kit/CD117, CD34, bcl-2, and Ki67. MAIN OUTCOME
      MEASURE(S): Immunostaining. RESULT(S): C-kit/CD117, CD34, bcl-2, and Ki67 were
      consistently expressed in the stroma of the basalis layer. Bcl-2 was restricted
      to the fetal uterine endometrium. CONCLUSION(S): By studying the
      immunolocalization of stem cell markers (i.e., c-kit, CD34, and bcl-2), we found
      that stem cells are present continuously in the uterine endometrium from the
      fetal period. The cells seem to be located mainly in the stroma of the basalis
      and to be independent of hormonal regulation to avoid cyclic shedding. A small
      number of latent stem cells dormant in the stroma of the basalis were found to
      have the potential for mesenchymal differentiation.

PMID- 14967382
TI  - Fast multicolor primed in situ protocol for chromosome identification in isolated
      cells may be used for human oocytes and polar bodies.
AB  - OBJECTIVE: To present and evaluate the use of a new ultra-fast multicolor primed
      in situ (PRINS) procedure for karyotyping human oocytes and first polar bodies.
      DESIGN: In situ chromosomal identification on isolated cells, using combinations
      of specific primers for chromosomes 1, 7, 9, 16, and 18 and fluorescent
      nucleotides. SETTING: Sixteen unfertilized oocytes were obtained from women
      participating in an IVF program. PATIENT(S): Five patients undergoing an IVF-ET.
      INTERVENTION(S): In vitro unfertilized oocytes were fixed on slides, and
      sequential PRINS reactions were performed on each preparation. MAIN OUTCOME
      MEASURE(S): Ultrarapid in situ identification of three or four chromosomes on
      oocyte and polar body chromosome spreads. RESULT(S): On the basis of the direct
      in situ mixing of the colors of fluorochromes (FITC, TRITC, Cascade Blue) that
      were incorporated in sequential PRINS reactions, this method allows rapid and
      efficient labeling of three or four individual chromosomes. Each PRINS reaction
      consists of a unique 4- to 6-minute step for both in situ annealing and
      elongation. The procedure can be combined with fluorescence in situ hybridization
      (FISH) reactions. CONCLUSION(S): By simplifying the multicolor PRINS procedure,
      this new protocol should facilitate the use and adaptation of PRINS to chromosome
      screening. This approach could be used in parallel or in combination with FISH
      for efficient aneuploidy assessment on isolated cells.

PMID- 14967383
TI  - In vivo regulation of mRNA expression of vascular endothelial growth factor
      receptors (KDR and flt-1) in the human oviduct.
AB  - OBJECTIVE: To examine the localization of vascular endothelial growth factor
      receptors (VEGF-R) and the changes in VEGF-R messenger ribonucleic acid (mRNA)
      expression in various regions of the oviduct from fertile women throughout the
      ovulatory cycle. DESIGN: Prospective observational study. SETTING: University
      based obstetrics and gynecology department. PATIENT(S): Twenty-two women who
      underwent laparoscopic tubal sterilization or hysterectomy for a benign
      gynecological condition. INTERVENTION(S): The mucosal layer was isolated from the
      oviduct tissue. Immunohistochemistry and a semiquantitative reverse-transcriptase
      polymerase chain reaction (RT-PCR) was performed. MAIN OUTCOME MEASURE(S):
      Immunohistochemical localization of VEGF-R proteins in oviduct tissue, and the
      differences of VEGF-R mRNA expression in the various regions of the oviduct and
      in the various stages of the ovulatory cycle. RESULT(S): Immunohistochemical
      study localized VEGF-R, both KDR and flt-1, in the oviduct luminal epithelium,
      smooth muscle cells as well as blood vessels within the oviduct. Messenger RNA
      expression of KDR, but not flt-1, was significantly higher in the ampullary and
      infundibular regions than in the isthmus. Messenger RNA expression of flt-1, but
      not KDR, varied significantly in the oviduct along the course of an ovulatory
      cycle, with the highest level in the periovulatory stage. CONCLUSION(S): These
      results suggest that the two VEGF receptors may have different roles in the
      oviduct. Our data support a role for KDR in oviduct angiogenesis whereas flt-1
      appears to be important in the temporal regulation of oviductal secretion.

PMID- 14967384
TI  - Varicocele: a bilateral disease.
AB  - OBJECTIVE: To evaluate the prevalence of varicocele in the left and right
      spermatic veins in infertile men by several methods of examination. DESIGN:
      Prospective study. SETTING: Andrology unit of a department of obstetrics and
      gynecology, and interventional radiology unit of the radiology department at a
      tertiary care facility. PATIENT(S): Two hundred eighty-six infertile men
      evaluated for varicocele. INTERVENTION(S): Patients underwent evaluation for
      infertility. Physical examination was followed by contact thermography, Doppler
      sonography, and venography of both testes. MAIN OUTCOME MEASURE(S): We measured
      the prevalence of varicocele in the left and right spermatic veins in infertile
      men, and the response of semen parameters after embolization of internal
      spermatic vein. RESULT(S): Varicocele was detected by one of the noninvasive
      methods and confirmed by venography in 255 patients (89.2%): the left site in 45
      (17.6%), the right side in 4 (1.5%), and bilaterally in 206 (80.8%). All patients
      were treated by embolization. Mean sperm concentration increased from 6.12 +/-
      1.02 to 21.3 +/- 1.69 million/mL; mean sperm motility from 16.81 +/- 1.51 to
      35.90 +/- 1.41%; and mean sperm morphology from 9.75 +/- 0.85 to 16.92 +/- 1.17%.
      Pregnancy rate was 43.5%. CONCLUSION(S): The present study finds that what was
      traditionally considered a predominantly unilateral anatomical abnormality
      apparently has a strikingly high bilateral prevalence (80.7%). This may suggest
      that we should consider varicocele a bilateral disease. The second finding is the
      high rate of varicocele detected by venography, thermography, and sonography when
      compared with physical examination results. Our study may have important
      implications for treatment, indicating that patients with clinical evidence of
      unilateral left varicocele should be carefully evaluated for bilateral
      varicocele.

PMID- 14967386
TI  - A detachable porous vaginal mold facilitates reconstruction of a modified McIndoe
      neovagina.
AB  - OBJECTIVE: To release a new design for a detachable porous vaginal mold to
      facilitate reconstruction of a modified McIndoe vaginal mold. DESIGN: We
      constructed a detachable, porous vaginal mold with a plastic laboratory
      centrifuge tube with multiple holes throughout the entire tube. SETTING: Patients
      in a national tertiary medical center. PATIENT(S): Four patients of congenital
      vaginal agenesis received the modified McIndoe procedure. INTERVENTION(S): Two
      full-thickness skin grafts removed from the inguinal region were used to cover
      the detachable porous plastic vaginal mold; the mold was then inserted into the
      neovaginal cavity and kept in place by sutures between the mold and labia majora.
      The vaginal mold was removed on day 12 after the operation. All patients adhered
      to the follow-up instructions. MAIN OUTCOME MEASURE(S): Description of the
      accessibility of a neovaginal mold. RESULT(S): The vaginal mold is helpful in
      taking care of the vaginal wound in that it allows easy removal of wound
      secretion and local cleansing douches. All grafts took completely and recovered
      well. No detachment of the graft occurred. CONCLUSION(S): The advantages of the
      detachable porous vaginal mold made from a plastic centrifuge tube are that it is
      readily available, allows for easy wound care, and, as a fixed point, prevents
      graft detachment or inversion and thus may lead to a promising result for a
      modified McIndoe vaginal reconstruction.

PMID- 14967385
TI  - A new power Doppler ultrasound guiding technique for improved testicular sperm
      extraction.
AB  - OBJECTIVE: To develop a noninvasive procedure that employs image processing of
      power Doppler ultrasound (PDUS) images of several orthogonal cross-sections of
      the testis to construct a three-dimensional (3D) mapping of preferential
      testicular regions in which spermatozoa are most likely to be found in
      nonobstructive azoospermic testes. DESIGN: Clinical study. SETTING: Ultrasound
      and andrology units in a large university-affiliated municipal hospital.
      PATIENT(S): Twenty-four nonobstructive azoospermic men. INTERVENTION(S): Before
      testicular sperm extraction was performed, PDUS images were acquired at seven
      cross-sections to reconstruct a 3D testicular vascularity index (TVI) matrix for
      spatial mapping of testicular regions in which spermatozoa are most likely to be
      found. The predictions based on TVI values of 107 regions were compared with the
      biopsy results. MAIN OUTCOME MEASURE(S): Prediction of presence or absence of
      spermatozoa by TVI values. RESULT(S): The prediction rate of the TVI matrix for
      the presence or absence of spermatozoa was 74.8%. The positive predicted value
      was 72%, negative predicted value was 75.6%, and specificity was 89.8%, but
      sensitivity was 47.3%. CONCLUSION(S): Our technique may obviate the need for
      arbitrary multiple biopsies that inflict some degree of damage upon testicular
      tissue and may increase the success rate of identifying viable spermatozoa in
      testicular tissue.

PMID- 14967387
TI  - Separation of human immunodeficiency virus type 1 from motile sperm by the double
      tube gradient method versus other methods.
AB  - OBJECTIVE: To compare a new sperm-processing device, utilizing a double tube and
      gradient, with other commonly used sperm-processing methods for their abilities
      to exclude human immunodeficiency virus type 1 (HIV-1) from the motile sperm
      fraction while retaining maximum sperm yield. DESIGN: Laboratory experiments.
      SETTING: Academic research environment. PATIENT(S): Healthy HIV-1 seronegative
      men between the ages of 25 and 55. INTERVENTION(S): Semen samples were spiked
      with HIV-1 (MN HIV-1 strain; range of concentrations: 10(-1)-10(6) TCID(50)) and
      subjected to one of the following sperm-processing methods: double sperm tube
      with discontinuous gradient of sperm separation medium formed inside (double tube
      gradient), conventional single tube gradient, swim-up or single tube gradient
      followed by swim-up (gradient/swim-up), which is the method currently used to
      minimize HIV-1 in semen used for assisted reproductive technology (ART)
      procedures. For the gradient techniques, Percoll, ISolate, and PureSperm sperm
      separation media were compared for efficacy of HIV-1 removal. The amount of HIV-1
      remaining in the motile sperm pellet after processing was measured by reverse
      transcription-polymerase chain reaction (RT-PCR), NucliSens assay, or
      quantitative HIV-1 culture. A hemacytometer was used to microscopically assess
      motile sperm count. MAIN OUTCOME MEASURE(S): HIV-1 RNA copy number, decrease in
      HIV-1 TCID(50), motile sperm yield. RESULT(S): The double tube gradient technique
      was significantly better than all other methods in the removal of HIV-1 from the
      motile sperm fraction, and produced significantly higher sperm yields in
      comparison with the gradient/swim-up method. CONCLUSION(S): The double tube
      gradient technique is a relatively simple and effective method that reduces the
      risk of infection by HIV-1 while producing good sperm recovery.

PMID- 14967388
TI  - Fallopian tube sperm perfusion versus intrauterine insemination in unexplained
      infertility: a randomized, prospective, cross-over trial.
AB  - OBJECTIVE: To compare the results of fallopian tube sperm perfusion (FSP) versus
      standard intrauterine insemination (IUI) in patients with unexplained infertility
      undergoing controlled ovarian hyperstimulation (COH). DESIGN: Randomized,
      prospective, cross-over study. SETTING: Reproductive medicine unit of a
      university hospital. PATIENT(S): Fifty-six couples with unexplained infertility.
      INTERVENTION(S): COH was induced by recombinant FSH and monitored by serial
      transvaginal ultrasound. On the day of hCG administration during the first
      treatment cycle, patients were randomized to either IUI or FSP. Thereafter, in
      case no pregnancy was achieved, patients went on being treated with FSP and IUI
      in alternate cycles. A maximum of four treatment cycles per couple was performed.
      FSP was performed using a pediatric Foley's catheter inseminating 4 mL of sperm
      enriched suspension; a Kremer-Delafontaine catheter delivering 0.5 mL of sperm
      suspension was used for IUI. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate per
      cycle. RESULT(S): One hundred twenty-seven cycles (58 FSP, 69 IUI) were
      performed. The clinical pregnancy rate per cycle was 21.7% for IUI and 8.6% for
      FSP, respectively. No major adverse effects were recorded for either technique.
      CONCLUSION(S): After COH, FSP is less effective than IUI in couples with
      unexplained infertility.

PMID- 14967389
TI  - The feasibility of embryo donation.
AB  - Transfer of donated frozen embryos of various quality to recipients resulted in a
      delivered pregnancy rate of 36.8% per transfer. Hopefully these data will
      encourage other in vitro fertilization programs to set up similar programs.

PMID- 14967390
TI  - Comparison of embryo transfer on day 2, day 3, and day 6: a prospective
      randomized study.
AB  - A prospective randomized study of 243 embryo transfers revealed that the use of
      blastocysts in assisted reproductive technology is not more effective than the
      use of day 2 and day 3 embryos.

PMID- 14967391
TI  - Increased serum polychlorobiphenyl levels in Belgian women with adenomyotic
      nodules of the rectovaginal septum.
AB  - The sum of bulk polychlorobiphenyl levels was significantly higher in women with
      rectovaginal adenomyosis than in women with endometriosis and controls.

PMID- 14967392
TI  - Dexamethasone reduces androgen levels in metformin-treated patients with
      polycystic ovary syndrome.
AB  - Women with polycystic ovary syndrome treated with metformin and lifestyle advice
      were studied. Additional treatment with dexamethasone, but not with
      bromocriptine, further reduced circulating androgen levels.

PMID- 14967393
TI  - Patients' opinions regarding preimplantation genetic diagnosis in a Latin
      American fertility clinic.
AB  - Patients' opinions concerning the use of preimplantation genetic diagnosis were
      evaluated in a fertility clinic with a specially designed questionnaire. The
      results of this study suggest that for couples with fertility problems, an embryo
      with severe genetic abnormalities has a different moral status than a healthy
      one.

PMID- 14967394
TI  - Relationship between central obesity and cardiovascular hemodynamic indices in
      postmenopausal women.
AB  - The impact of body fat distribution on cardiovascular hemodynamics in
      postmenopausal women is not clear. In a sample of healthy postmenopausal women,
      greater central body fat distribution was associated with higher peripheral
      resistance, triglycerides, and total cholesterol as well as lower cardiac and
      stroke indexes.

PMID- 14967395
TI  - Maternal serum inhibin A levels may predict pregnancy outcome in women with
      threatened abortion.
AB  - Determination of maternal serum inhibin A in women with threatened abortion may
      be helpful in predicting the failure of pregnancies.

PMID- 14967396
TI  - Assessment of the effects of varicocelectomy on the thermoregulatory control of
      the scrotum.
AB  - Infrared functional imaging was successfully used to assess restoration of the
      normal thermal control of the scrotum after surgical treatment of varicoceles.
      The technique may be used to study the relationship between impaired scrotal
      thermoregulation and spermatogenesis.

PMID- 14967397
TI  - Duration of gonadotropin-releasing hormone antagonist administration does not
      affect the outcome of subsequent frozen-thawed cycles.
AB  - The duration of administration of GnRH antagonist in cycles stimulated with
      recombinant FSH for IVF/intracytoplasmic sperm injection does not affect the
      probability of blastocyst replacement and of achieving an ongoing pregnancy in
      subsequent frozen-thawed cycles.

PMID- 14967398
TI  - Dose reduction and discontinuation of alendronate in postmenopausal osteoporotic
      women who were receiving estrogen therapy.
AB  - Low-dose alendronate is as effective as standard-dose alendronate, and its
      effects continue after drug withdrawal in postmenopausal osteoporotic women who
      are being treated with estrogen.

PMID- 14967399
TI  - In vitro maturation of oocytes.

PMID- 14967401
TI  - Comparison of recombinant hCG and urinary hCG.

PMID- 14967403
TI  - Symbols of fertility?

PMID- 14967405
TI  - Enzymes and adhesion formation.

PMID- 14967407
TI  - Plasminogen activator inhibitor contributes to the coronary wall thickening in
      patients with angiographically normal coronary.
AB  - INTRODUCTION: Angiographically normal coronary arteries have concealed intimal
      thickening that importantly contribute to coronary arterial disease activity.
      Increased plasma levels of plasminogen activator inhibitor (PAI) are associated
      with myocardial infarction and atherosclerosis. However, it remains unclear
      whether the PAI contributes to vascular wall thickening detected by intravascular
      ultrasound (IVUS) in normal coronary angiogram. The aim of this study was to
      evaluate if the PAI activity contributes to the extent of atherosclerotic changes
      in angiographically normal coronary arteries using IVUS technique. MATERIALS AND
      METHODS: We studied 33 consecutive patients with normal coronary angiograms.
      These patients were divided into a high level of plasma PAI activity group (H
      PAI; n=12) and a normal range of PAI activity group (N-PAI; n=21), according to
      the plasma PAI activity levels. RESULTS: The average of "percent intima+media
      area (%I+M area)" and "maximal intima+media (I+M) thickness" were significantly
      greater in the H-PAI group as compared with those in the N-PAI group (p<0.05).
      Minimal lumen diameter and lumen area were comparable between these groups. The
      plasma PAI activity level was the independent predictor of increase in maximal
      I+M thickness, in multiple regression analysis with the traditional risk factors
      as covariates. CONCLUSIONS: Thickened intima+media of angiographically normal
      coronary arteries were associated with high plasma level of PAI activity,
      independently of other traditional risk factors. PAI may contribute to the
      pathogenesis of coronary intimal thickening that might increase coronary arterial
      tone.

PMID- 14967408
TI  - Associated thrombophilic defects in essential thrombocythaemia: their
      relationship with clinical manifestations.

PMID- 14967409
TI  - Serotonin-2A receptor gene polymorphisms are associated with serotonin-induced
      platelet aggregation.

PMID- 14967410
TI  - Genetic assessment of cardiovascular risk factors in the Greek Cypriot
      population.

PMID- 14967411
TI  - Association of C807T, Pl(A), and -5 C/T Kozak genotypes with density of
      glycoprotein receptors on platelet surface.
AB  - This study investigates whether three platelet glycoprotein (GP) polymorphisms,
      C807T in GP Ia, Pl(A1/A2) in GP IIIa, and -5 T/C Kozak in GP Ibalpha gene,
      influence the density of the three important adhesion and activation receptors on
      the platelet surface. Fifty-four healthy donors were genotyped according to the
      three polymorphisms, and densities of the corresponding GPs were measured by flow
      cytometry. Our study confirmed the association between C807T polymorphism and
      platelet surface expression of GP Ia-IIa and GP Ia and demonstrated that the
      density of GP Ibalpha or GP IX is not associated with the Kozak polymorphism.
      Although the Pl(A1/A2) polymorphism did not affect the expression of GP IIb-IIIa
      and GP IIIa on the platelet surface, flow-cytometric analysis employing murine
      monoclonal antibody SZ21 against GP IIIa can be applied to distinguish Pl(A1/A1)
      and Pl(A1/A2) polymorphism.

PMID- 14967412
TI  - The nontoxic mushroom Auricularia auricula contains a polysaccharide with
      anticoagulant activity mediated by antithrombin.
AB  - An acidic polysaccharide with anticoagulant activity was isolated from the edible
      mushroom Auricularia auricula using water, alkali or acid extracts. The alkali
      extract showed the highest anticoagulant activity and was thereby further
      purified using gel filtration chromatography. Specific anticoagulant activity of
      the purified polysaccharide was 2 IU/mg and its average mass was approximately
      160 kDa. The polysaccharide from this species of mushroom contains mainly
      mannose, glucose, glucuronic acid and xylose but no sulfate esters. Its
      anticoagulant activity was due to catalysis of thrombin inhibition by
      antithrombin but not by heparin cofactor II. Inhibition of Factor Xa by
      antithrombin was not catalyzed by the polysaccharide. The glucuronic acid
      residues were essential for the anticoagulant action of the mushroom
      polysaccharide since the activity disappeared after reduction of its carboxyl
      groups. In ex vivo tests using rats orally fed with the polysaccharide, we
      observed an inhibitory effect on platelet aggregation as observed with aspirin, a
      well-known antiplatelet agent. The polysaccharides from these mushrooms may
      constitute a new source of compounds with action on coagulation, platelet
      aggregation and, perhaps, on thrombosis.

PMID- 14967413
TI  - Astrocyte regulation of human brain capillary endothelial fibrinolysis.
AB  - INTRODUCTION: Astrocytes are known to regulate a wide variety of brain
      endothelial cell functions. Prior work, using a mixed species co-culture system,
      has shown astrocyte regulation of brain capillary endothelial expression of key
      hemostasis factors tissue plasminogen activator (tPA) and its inhibitor,
      plasminogen activator inhibitor-1 (PAI-1). The purpose of this study is to define
      the fibrinolytic regulatory role of human astrocytes on human brain capillary
      endothelial cells. MATERIALS AND METHODS: We used a blood-brain barrier model
      consisting of human astrocytes grown on transwell membrane inserts and co
      cultured with human brain capillary endothelial cells. Following 48 h co-culture,
      we analyzed both endothelial mono-cultures and astrocyte-endothelial co-cultures
      for expression of tPA and PAI-1 mRNA, protein, and activity. RESULTS AND
      CONCLUSIONS: There were significant changes for both tPA and PAI-1 mRNA:tPA mRNA
      levels were decreased in co-cultures (55+/-16% of mono-cultures, p<0.0005) and
      PAI-1 mRNA levels were increased 144+/-38%, compared to mono-cultures (p<0.005).
      Co-cultures produced a 54% reduction in tPA protein (12.7+/-3.8 vs. 27.5+/-7.1
      ng/ml, p<0.005) and a 24% increase in PAI-1 protein (117.5+/-3.2 vs. 94.9+/-5.9
      ng/ml, p<0.0005). TGF-beta neutralizing antibody attenuated the observed changes
      in both tPA and PAI-1. These data indicate that human astrocytes regulate human
      brain capillary fibrinolysis in vitro by inhibiting tPA and enhancing PAI-1
      expression. This regulation is mediated, in part, by transforming growth factor
      beta. Our findings provide further evidence for the role of astrocytes in brain
      specific hemostasis regulation.

PMID- 14967414
TI  - Administration of a small molecule tissue factor/factor VIIa inhibitor in a non
      human primate thrombosis model of venous thrombosis: effects on thrombus
      formation and bleeding time.
AB  - INTRODUCTION: Pharmacological treatment of deep vein thrombosis (DVT) in the
      future may target inhibitors of specific procoagulant proteins. This study used a
      non-human primate model to test the effect of PHA-798, a specific inhibitor of
      the tissue factor/Factor VIIa complex (TF/VIIa), on venous thrombus formation.
      MATERIALS AND METHODS: PHA inhibits the TF/VIIa complex with an IC(50) of 13.5 nM
      (K(i) 9 nM) and is more than 2000-fold selective for the TF/VIIa complex with
      respect to IC(50)s for factor Xa and thrombin. In the model, a thrombogenic
      surface was introduced into the vena cava of a primate, and the amount of
      thrombus accumulated after 30 min was determined. RESULTS: PHA-798 reduced
      thrombus formation on the thrombogenic surface in a dose-dependent manner (56+/
      1.9% and 85+/-0.3% inhibition with 100 and 200 microg/kg/min PHA-798,
      respectively) indicating that the model is sensitive to TF/VIIa inhibition.
      Treatment with 1 mg/kg intravenous (IV) acetyl salicylic acid (ASA) resulted in
      only a slight (4-12%), non-significant inhibition of thrombus formation. However,
      the combination of 100 microg/kg/min PHA-798 and 1 mg/kg ASA resulted in an 89%
      inhibition of thrombus formation. Additionally, while ASA alone increased
      bleeding time (BT) from 3.3 min at baseline to 4.6 min following treatment,
      addition of PHA-798 (100 microg/kg/min) to ASA did not significantly increase the
      BT further (4.7 min). CONCLUSIONS: The results of this study indicate that
      inhibition of TF/VIIa may be safe and effective for the prevention of the
      proprogation of venous thrombosis and that the combination of ASA and PHA may
      provide increased efficacy with little change in safety.

PMID- 14967415
TI  - A quantitative real-time PCR method for tissue factor mRNA.
AB  - BACKGROUND: Tissue factor (TF) is primarily known for its function to initiate
      blood coagulation. The range of in vivo expression of TF is wide and requires a
      dynamic assay for monitoring. A general method for TF mRNA quantitation that is
      dynamic, sensitive and applicable to a variety of experimental systems or
      clinical situations is therefore desirable. OBJECTIVES: To develop a method for
      sensitive and dynamic quantitation of TF mRNA in human blood cells. METHODS: TF
      mRNA expression was analysed and evaluated in monocyte isolations, in whole blood
      (healthy volunteers and patients scheduled for percutaneous coronary
      intervention, PCI) and in a panel of human cell lines. RNA was extracted, reverse
      transcribed and subjected to real-time PCR amplification, according to the TaqMan
      technology. A TF plasmid was constructed as calibrator of the assay. Two
      housekeeping genes used as endogenous controls for cDNA quality and integrity
      were evaluated. RESULTS: The assay was linear by seven orders of magnitude and
      detected down to 10(2) copies of the TF plasmid. The coefficient of variation was
      4% intra-assay and 28% between the assays when using beta2MG as endogenous
      control. The beta-actin gene expression was induced by treatment with
      lipopolysaccharide (LPS) in blood leukocytes and could not be used as an
      endogenous control. However, beta2MG showed only minor variations upon treatment
      with LPS. The TF mRNA and antigen expression, measured in a Western blot,
      correlated well (R(2)=0.903) in a panel of 11 human cell lines. CONCLUSIONS: We
      have established a method for sensitive and dynamic quantitation of TF mRNA in
      experimental systems and for clinical situations.

PMID- 14967416
TI  - Secretion of tissue plasminogen activator and plasminogen activator inhibitor 1
      during cardiopulmonary bypass.
AB  - INTRODUCTION: Cardiopulmonary bypass (CPB) is associated with elevated tissue
      plasminogen activator (t-PA) levels during CPB and increased plasminogen
      activator inhibitor 1 (PAI-1) levels post-operatively. The goal of this study was
      to estimate the rate of t-PA and PAI-1 secretion in vivo, before, during and
      after CPB. MATERIALS AND METHODS: Estimated rates of t-PA and PAI-1 secretion
      were based on measured levels of active and total t-PA, and active and total PAI
      1, obtained before, during and after CPB from nine males, combined with a
      computer model of each patient's vascular system that continuously accounted for
      secretion, clearance, hemodilution, blood loss and transfusion. RESULTS AND
      CONCLUSIONS: At baseline, the average t-PA and PAI-1 secretion rates were 0.74+/
      0.33 and 1.28+/-0.74 pmol/s, respectively. Within 5 min of CPB initiation, t-PA
      secretion increased six-fold to 4.41+/-2.58 pmol/s, while PAI-1 secretion was
      unchanged, resulting in a six-fold increase in active t-PA levels. t-PA secretion
      remained elevated throughout CPB and into the early post-operative period.
      Average PAI-1 secretion did not start to increase until the end of CPB. By 2 h
      after surgery, average PAI-1 secretion had increased 15-fold to 19.60+/-17.10
      pmol/s, resulting in reduced levels of active t-PA even though t-PA secretion was
      still elevated. We conclude that CPB induces an immediate sustained increase in t
      PA secretion followed by a delayed progressive increase in PAI-1 production.
      Variations in the level of active t-PA are a function of the relative rates of t
      PA versus PAI-1 secretion at different times during and after surgery.

PMID- 14967417
TI  - Renal toxicity after bone marrow transplantation.

PMID- 14967418
TI  - Preservation of oral health-related quality of life and salivary flow rates after
      inverse-planned intensity- modulated radiotherapy (IMRT) for head-and-neck
      cancer.
AB  - PURPOSE: To assess whether comprehensive bilateral neck intensity-modulated
      radiotherapy (IMRT) for head-and-neck cancer results in preserving of oral health
      related quality of life and sparing of salivary flow in the first year after
      therapy. METHODS AND MATERIALS: Twenty-three patients with head-and-neck cancer
      (primary sites: nasopharynx [5], oral cavity [12], oropharynx [3], and all others
      [3]) were accrued to a Phase I-II trial. Inverse planning was carried out with
      the following treatment goals: at least 1 spared parotid gland (defined as the
      volume of parotid gland outside the planning target volume [PTV]) to receive a
      median dose of less than 20 Gy; spinal cord, maximum 45 Gy; PTV(1) to receive a
      median dose of 50 Gy; PTV(2) to receive a median dose of 60 Gy (postoperative
      setting, n = 15) or 66-70 Gy (definitive radiotherapy setting, n = 8). Treatment
      was delivered with 6 and 15 MV photons using a "step-and-shoot" technique on a
      Varian 2300 EX linac with 120-leaf Millenium MLC. Unstimulated and stimulated
      whole-mouth salivary flow rates were measured, and patients completed the
      University of Washington instrument (UWQOL) and a separate xerostomia
      questionnaire (XQOL) in follow-up. RESULTS: Early functional outcome end point
      data are available at the 1-, 3-, and 12-month follow-up time points for 22, 22,
      and 18 patients, respectively. The combined mean parotid dose was 30.0 Gy (95%
      confidence interval: 26.9-33.1). The differences from baseline in mean overall
      UWQOL scores at 1, 3, and 12 months postradiotherapy were -0.24, 0.32, and 4.28,
      not significantly different from zero (p = 0.89, p = 0.87, p = 0.13). None of the
      UWQOL individual domain scores related to oral health (pain, eating-chewing,
      eating-swallowing, and speech) at 1, 3, or 12 months were significantly different
      from baseline. Both unstimulated and stimulated whole-mouth flow was variably
      preserved. Unstimulated salivary flow at 1 and 12 months was inversely correlated
      with combined mean parotid dose (p = 0.014, p = 0.0007), whereas stimulated
      salivary flow rates at 3 and 12 months were also correlated with combined mean
      parotid dose (p = 0.025, p = 0.0016). Combined maximum parotid dose was
      correlated with unstimulated flow rate at 12 months (p = 0.02, r = -0.56) and
      stimulated flow rate at 1 and 12 months (p = 0.036, r = -0.45; p = 0.0042, r = 
      0.66). The proportion of patients reporting total XQOL scores of 0 or 1 (no or
      mild xerostomia) did not diminish significantly from baseline at 1, 3, or 12
      months (p = 0.72, p = 0.51, p = 1.0). Unstimulated and stimulated flow at 1 month
      was inversely correlated with total XQOL score at 12 months (p = 0.025, p =
      0.029). CONCLUSIONS: Oral health-related quality of life (HRQOL) was highly
      preserved in the initial 12 months after IMRT, as assessed with separate,
      validated instruments for xerostomia-specific quality of life and oral HRQOL. In
      general, patients with better-preserved unstimulated salivary flow rates tended
      to report lower xerostomia scores. Whole-mouth salivary flow rates post IMRT were
      inversely correlated with combined mean parotid doses. Longer follow-up is
      required to assess to what extent HRQOL is favorably maintained.

PMID- 14967419
TI  - A multinational, randomized phase III trial of iseganan HCl oral solution for
      reducing the severity of oral mucositis in patients receiving radiotherapy for
      head-and-neck malignancy.
AB  - PURPOSE: Oral mucositis (OM) causes significant morbidity during the course of
      radiotherapy (RT) treatment of head-and-neck cancer. It is hypothesized that
      infection plays a role in the development of OM. We tested the efficacy of
      iseganan HCl (iseganan), a synthetic peptide with broad-spectrum antimicrobial
      activity, for preventing RT-associated OM. METHODS: A multinational, randomized,
      double-blind, controlled trial was performed on patients receiving primary RT,
      primary chemoradiotherapy or postoperative RT. Patients were randomized to
      receive iseganan oral solution plus standard-of-care oral hygiene (SOC), placebo
      plus SOC, or SOC alone throughout the RT administration period. The severity of
      OM was assessed by NCI-CTC scoring and clinical symptoms by patient
      questionnaire. RESULTS: A total of 545 patients were randomized to the study.
      Nine percent of the patients in both the iseganan and placebo groups did not
      develop ulcerative OM (Grades 2, 3, 4) (p = 0.998) whereas only 2% of the
      patients receiving SOC alone remained free of oral ulceration (p = 0.049). The
      maximum severity of mouth pain and difficulty swallowing did not differ in
      patients treated with iseganan or placebo. However, patients in both intervention
      groups reported less mouth pain and difficulty swallowing than did patients
      receiving SOC alone. Nausea was the only adverse event that occurred with >/=5%
      increased frequency in the iseganan group than in either the placebo or SOC
      groups (51% vs. 42% vs. 46%). Adverse events leading to study drug
      discontinuation and death did not differ significantly between groups.
      CONCLUSION: Iseganan oral solution was safe but did not reduce the risk for
      developing ulcerative OM relative to placebo. Intensified oral hygiene or the
      administration of the vehicle used to deliver study drug in this trial appears to
      have reduced the risk and severity of OM. Our results suggest that antimicrobial
      intervention may not meaningfully affect the pathogenesis of radiation-induced
      OM.

PMID- 14967420
TI  - Initial experience using intensity-modulated radiotherapy for recurrent
      nasopharyngeal carcinoma.
AB  - PURPOSE: To report our initial experience on the feasibility, toxicity, and tumor
      control using intensity-modulated radiotherapy (IMRT) for retreatment of
      recurrent nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: A total of 49
      patients with locoregional recurrent carcinoma in the nasopharynx were treated
      with IMRT between January 2001 and February 2002 at the Sun Yat-Sen University
      Cancer Center, Guangzhou, China. The average time to the nasopharyngeal
      recurrence was 30.2 months after initial conventional RT. The median isocenter
      dose to the nasopharynx was 70 Gy (range 60.9-78.0) for the initial conventional
      RT. All patients were restaged at the time of recurrence according to the 1992
      Fuzhou, China staging system on NPC. The number of patients with Stage I, II, III
      and IV disease was 4, 9, 10, and 26, respectively. T1, T2, T3, and T4 disease was
      found in 4, 9, 11, and 25 patients, respectively. N0, N1, N2, and N3 disease was
      found in 46, 2, 0, and 1 patient, respectively. Invasion of the nasal cavity,
      maxillary sinus, ethmoid sinus, sphenoid sinus, and cavernous sinus and erosion
      of the base of the skull was found in 8, 1, 3, 8, 15, and 20 patients,
      respectively. The gross tumor volume (GTV) was contoured according to the
      International Commission on Radiation Units and Measurements (ICRU) Report 62
      guidelines. The critical structures were contoured, and the doses to critical
      structures were constrained according to ICRU 50 guidelines. The GTV in the
      nasopharynx and positive lymph nodes in the neck received a prescription dose of
      68-70 Gy and 60 Gy, respectively. All patients received full-course IMRT. Three
      patients who had positive lymph nodes were treated with five to six courses of
      chemotherapy (cisplatin + 5-fluorouracil) after IMRT. RESULTS: The treatment
      plans showed that the percentage of GTV receiving 95% of the prescribed dose
      (V(95-GTV)) was 98.5%, and the dose encompassing 95% of GTV (D(95-GTV)) was 68.1
      Gy in the nasopharynx. The mean dose to the GTV was 71.4 Gy. The average doses of
      the surrounding critical structures were much lower than the tolerable
      thresholds. At a median follow-up of 9 months (range 3-13), the locoregional
      control rate was 100%. Three cases (6.1%) of locoregional residual disease were
      seen at the completion of IMRT, but had achieved a complete response at follow
      up. Three patients developed metastases at a distant site: two in the bone and
      one in the liver and lung at 13 months follow-up. Acute toxicity (skin, mucosa,
      and xerostomia) was acceptable according to the Radiation Therapy Oncology Group
      criteria. Tumor necrosis was seen toward the end of IMRT in 14 patients (28.6%).
      CONCLUSION: The improvement in tumor target coverage and significant sparing of
      adjacent critical structures allow the feasibility of IMRT as a retreatment
      option for recurrent NPC after initial conventional RT. This is the first large
      series using IMRT to reirradiate local recurrent NPC after initial RT failed. The
      treatment-related toxicity profile was acceptable. The initial tumor
      response/local control was also very encouraging. In contrast to primary NPC,
      recurrent NPC reirradiated with high-dose IMRT led to the shedding of tumor
      necrotic tissue toward the end of RT. More patients and longer term follow-up are
      warranted to evaluate late toxicity and treatment outcome.

PMID- 14967421
TI  - Tailoring distant metastatic imaging for patients with clinically localized
      undifferentiated nasopharyngeal carcinoma.
AB  - PURPOSE: The 2000 practice guidelines of the National Comprehensive Cancer
      Network recommend World Health Organization Type 2-3 nasopharyngeal carcinoma
      (NPC) be staged for distant disease using chest X-ray and bone scan. Our aim was
      to evaluate these modalities plus liver ultrasonography for American Joint
      Committee on Cancer/International Union Against Cancer 1997 clinical Stage I-IVB
      NPC. METHODS AND MATERIALS: Between February 1999 and May 2002, all patients with
      clinical (examination plus CT/MRI of head and neck) Stage I-IVB undifferentiated
      NPC were prospectively evaluated for distant disease with chest X-ray, liver
      ultrasonography, and bone scan. Suspicious lesions underwent confirmatory
      investigation, and patients were reevaluated at 4 months. RESULTS: In the 139
      patients evaluated, the positive yield was 3.6% and prevalence was 5.8% (0.7%
      lung, 2.2% skeletal, and 2.9% liver metastases). The prevalence increased by N
      stage (p = 0.004) and overall stage (p = 0.05). Compared with N3 disease (odds
      ratio 1.0), the odds of metastases for N0, N1, and N2 disease was 0, 0.12, and
      0.33, respectively. The positive yield was 0%, 1.8%, 4.8%, and 14.3% for N0, N1,
      N2, and N3 disease, respectively. CONCLUSION: This is the first study to evaluate
      the use of distant staging investigations for American Joint Committee on
      Cancer/International Union Against Cancer 1997 staged NPC. We recommend
      alterations to the 2000 National Comprehensive Cancer Network guidelines as
      follows: high-risk (N3) disease should be fully staged with chest X-ray, bone
      scan, and liver ultrasonography; intermediate risk (N1 and N2) disease may be
      staged using all three modalities on an institutional basis. No evidence supports
      distant imaging for low-risk (N0 or Stage I) disease.

PMID- 14967422
TI  - Can post-RT neck dissection be omitted for patients with head-and-neck cancer who
      have a negative PET scan after definitive radiation therapy?
AB  - PURPOSE: A prospective, single institution study was conducted to evaluate the
      role of positron emission tomography with fluoro-deoxyglucose (FDG) before and
      after definitive radiation therapy for patients with head-and-neck cancer.
      Correlation with CT or MRI imaging and pathologic findings at the time of planned
      neck dissection was made. METHODS AND MATERIALS: Twelve patients with AJCC Stages
      III-IV cancer of the head and neck received CT or MRI and PET imaging before
      treatment with definitive radiation therapy. One month after completion of
      treatment, repeat CT or MRI and PET imaging was obtained. All images were
      reviewed independently by radiologists who were blind to the results of the other
      modality. Patients then underwent planned neck dissection. Pathologic correlation
      with posttreatment scans allowed calculation of the sensitivity, specificity,
      negative predictive value, and the positive predictive value for both CT/MRI and
      PET. RESULTS: Comparison of CT/MRI to PET obtained before definitive RT revealed
      both primary tumor and nodal disease were detected by both modalities in all
      cases where primary tumor was known. After RT, comparison of CT/MRI imaging to
      findings of neck dissection revealed a sensitivity of 90%, specificity of 100%,
      positive predictive value of 100%, and negative predictive value of 50%.
      Comparison of PET imaging with pathologic findings demonstrated sensitivity of
      45%, specificity of 100%, positive predictive value of 100%, and a negative
      predictive value of 14%. CONCLUSIONS: In this small series of patients, the
      presence of a positive PET 1 month after RT accurately indicated the presence of
      residual disease in all cases; however, a negative PET indicated absence of
      disease in only 14%. Further investigation is warranted before FDG-PET should be
      used to determine whether post-RT neck dissection should be omitted.

PMID- 14967423
TI  - Toxic cure: Hyperfractionated radiotherapy with concurrent cisplatin and
      fluorouracil for Stage III and IVA head-and-neck cancer in the community.
AB  - PURPOSE: To evaluate efficacy and toxicity of the Duke University
      chemoirradiation regimen for locally advanced head-and-neck cancer in a regional
      community cancer center. METHODS AND MATERIALS: Between June 1998 and June 2002,
      50 patients with Stage III or IVA squamous cell carcinoma of the head and neck
      were treated definitively with concurrent combined modality therapy (CMT).
      Patients received accelerated, hyperfractionated radiotherapy (AFRT), 1.2-1.25 Gy
      b.i.d., to a median prescribed dose of 70 Gy. Chemotherapy consisted of cisplatin
      12 mg and fluorouracil 600 mg/m(2) daily for 5 consecutive days during Weeks 1
      and 6, followed by two cycles after AFRT. Patients with N2-N3 neck disease (n =
      21; 42%) were considered for neck dissection depending on their response to AFRT
      and chemotherapy. Twenty-nine patients with Stage III and IVA disease treated
      between 1991 and 1997 with definitive RT alone served as historical controls.
      RESULTS: Forty-nine patients (98%) in the CMT group completed the prescribed AFRT
      and 38 (76%) completed four cycles of chemotherapy. Three of 8 patients who
      underwent neck dissection had a pathologically complete response. The median
      follow-up for all patients was 23 months. The actuarial progression-free survival
      rate at 2 years was 75% for the CMT group vs. 40% (p <0.01) for the RT group. The
      overall survival rate was 80% and 43% (p <0.01), respectively, for the CMT and RT
      groups. Acute Radiation Therapy Oncology Group Grade 3 toxicities for the CMT
      group were mucosal (n = 50; 100%), skin (n = 9; 18%), and hematologic (n = 3;
      6%). Late Grade 3-4 toxicities consisted of pharyngeal stricture (n = 7; 14%),
      laryngeal chondritis (n = 3; 6%), osteoradionecrosis (n = 2; 4%), and peripheral
      neuropathy (n = 1; 2%). CONCLUSION: This aggressive regimen of AFRT with
      concurrent cisplatin and fluorouracil with or without neck dissection is feasible
      in the community setting for patients with Stage III and IVA head-and-neck
      cancer. Early results indicated excellent survival, albeit with universal acute
      mucosal, and considerable, although acceptable, late toxicity.

PMID- 14967424
TI  - Long-term results of radiotherapy for intracranial germinoma: a multi
      institutional retrospective review of 126 patients.
AB  - PURPOSE: Optimal management of radiotherapy (RT) for intracranial germinoma
      remains controversial. This study was conducted to evaluate the long-term results
      of RT in patients with these tumors. METHODS AND MATERIALS: The study group
      consisted of 126 patients with intracranial germinoma (50 patients with
      pathologically verified germinoma and 76 clinically diagnosed with germinoma by
      clinical and neuroradiologic signs) who were treated by RT alone between 1980 and
      2001. The median age at diagnosis was 17 years (range, 2-47), and various
      radiation doses and treatment fields were used. Serum human chorionic
      gonadotropin (hCG) levels were elevated in 18 patients. The median follow-up of
      the 114 surviving patients was 122 months (range, 13-263). RESULTS: The 10-year
      actuarial overall survival and cause-specific survival rate for all patients was
      90% and 95%, respectively. The 10-year actuarial cause-specific survival rate for
      patients with and without elevated hCG levels was 94%. Relapses were noted in 10
      patients, 7 of whom died of the disease. No in-field relapses at primary sites
      were observed in 72 patients treated with total doses of 40-50 Gy. The incidence
      of spinal relapses was 4% (2 of 56) for patients treated with spinal irradiation
      and 3% (2 of 70) for those without spinal irradiation. After a median 10-year
      follow-up, 54 (92%) of 59 patients with tumors not involving the neurohypophyseal
      region and 42 (76%) of 55 patients with tumors involving the neurohypophyseal
      region had Karnofsky performance status scores of 90-100%. With regard to school
      education and occupation, 54 (92%) of 59 patients with tumors not involving the
      neurohypophyseal region and 39 (71%) of 55 patients with tumors involving the
      neurohypophyseal region were attending school or undertaking occupations.
      Hormonal replacement therapy was required in 50 (44%) of 114 surviving patients
      before RT; only 4 patients (4%), all with neurohypophyseal tumors, required
      hormonal replacement therapy after RT. Clinically evident severe neurocognitive
      dysfunctions were documented in 10 patients before RT, and no patients treated
      with total doses of <55 Gy developed apparent neurocognitive dysfunctions or
      other complications after RT. CONCLUSION: RT was a curative treatment for
      intracranial germinoma, and elevated serum hCG levels did not affect the
      prognosis of patients treated by RT alone. A total dose of 40-50 Gy to adequate
      treatment fields was effective in preventing intracranial relapse, and the
      incidence of spinal relapses was too low to warrant routine spinal irradiation.
      Karnofsky performance status scores, educational achievement, and the ability to
      work were generally good, particularly in patients with tumors that did not
      involve the neurohypophyseal region. Because most complications, such as hormonal
      deficiency and neurocognitive dysfunction, were documented before RT and newly
      diagnosed complications after RT were infrequent, the treatment toxicity faced by
      germinoma patients appears to be less than anticipated.

PMID- 14967425
TI  - Surgery with or without radiation therapy in the management of craniopharyngiomas
      in children and young adults.
AB  - PURPOSE: The optimal management of craniopharyngiomas remains controversial,
      especially in children and young adults. This study reports a single
      institution's experience with such patients. METHODS AND MATERIALS: Between 1974
      and 2001, 76 patients were treated for craniopharyngioma at the Children's
      Hospital of Philadelphia and the Hospital of University of Pennsylvania (HUP). Of
      these, 75 patients (97%) were evaluable with long-term follow-up. Although all
      patients underwent attempted gross total resection, 27 had documentation of less
      than total resection with 18 of these patients receiving immediate postoperative
      radiotherapy (RT). An additional 22 patients received RT at HUP after failing
      surgery alone. RESULTS: Median follow-up for all patients was 7.6 years. The 10
      year actuarial overall survival, relapse-free survival, and local control (LC)
      rates for all patients were 85%, 48%, and 53%, respectively. When comparing the
      57 patients treated with surgery alone to the 18 treated with subtotal resection
      (STR) followed by RT, a significant difference in LC rates at 10 years (42% vs.
      84%, respectively; p = 0.004) was noted. However, no statistically significant
      difference in overall survival was found between the two groups, because RT was
      highly effective as salvage therapy. Twenty-two patients at HUP treated with RT
      after relapse had a 10-year ultimate LC rate comparable to that of patients who
      received RT immediately after STR. CONCLUSION: RT given either immediately after
      STR or at relapse is effective in controlling craniopharyngiomas.

PMID- 14967426
TI  - Hypofractionated intensity-modulated radiotherapy for primary glioblastoma
      multiforme.
AB  - PURPOSE: A pilot study was designed to evaluate the safety and efficacy of a
      novel regimen of hypofractionated intensity-modulated radiotherapy (RT) in the
      adjuvant treatment of primary glioblastoma multiforme (GBM). The rationale of the
      study was to combine the potential radiobiologic advantage of hypofractionation
      to GBM with a highly conformal radiotherapeutic technique. The study was designed
      to measure the acute and chronic morbidity of patients treated with this regimen,
      response of GBM to the treatment, overall survival, and time to disease
      progression after therapy completion. METHODS AND MATERIALS: Twenty eligible
      patients were accrued between February 1999 and May 2000 for the study. All
      patients had Karnofsky performance scores of >/=70. All patients were treated
      with intensity-modulated RT using the NOMOS Peacock system. A dose of 50 Gy was
      delivered in 5-Gy daily fractions within 2 weeks to enhancing primary disease,
      residual tumor, or surgical cavity. Simultaneously, 30 Gy was prescribed in 3-Gy
      daily fractions to surrounding edema. The time to progression was measured with
      serial neurologic examinations and MRI or CT scans after RT completion. Acute and
      late toxicity was graded using Radiation Therapy Oncology Group neurotoxicity
      scores. RESULTS: Of the 20 patients, 18 were evaluated for outcome. The median
      time to disease progression was 6 months after RT completion. The median overall
      survival was 7 months after treatment completion. All recurrences were within 2
      cm of the operative bed. Neurotoxicity during therapy was minimal, with all
      patients experiencing Grade 0 or 1 toxicity. Late toxicity included 10 patients
      with Grade 0, 2 patients with Grade 2, and 3 patients with Grade 4 toxicity,
      manifesting as brain necrosis requiring surgical reexcision. The survival of the
      3 patients with brain necrosis was 23, 20, and 9 months. Mortality in all cases
      was the result of tumor recurrence, with no mortality resulting from brain
      necrosis. CONCLUSION: This regimen of hypofractionated intensity-modulated RT did
      not improve the time to disease progression or overall survival compared with
      historical experience using conventional fractionation. However, the treatment
      duration was reduced from 6 weeks to 2 weeks, which may be of palliative benefit
      in certain subsets of patients. This treatment regimen demonstrated a greater
      incidence of brain necrosis requiring surgical intervention; however, the 3
      patients experiencing this toxicity had longer survival times. Future
      investigation may be useful to determine which fraction size may be optimal for
      GBM when highly conformal RT is used in the adjuvant setting.

PMID- 14967427
TI  - Advantage of protons compared to conventional X-ray or IMRT in the treatment of a
      pediatric patient with medulloblastoma.
AB  - PURPOSE: To compare treatment plans from standard photon therapy to intensity
      modulated X-rays (IMRT) and protons for craniospinal axis irradiation and
      posterior fossa boost in a patient with medulloblastoma. METHODS: Proton planning
      was accomplished using an in-house 3D planning system. IMRT plans were developed
      using the KonRad treatment planning system with 6-MV photons. RESULTS:
      Substantial normal-tissue dose sparing was realized with IMRT and proton
      treatment of the posterior fossa and spinal column. For example, the dose to 90%
      of the cochlea was reduced from 101.2% of the prescribed posterior fossa boost
      dose from conventional X-rays to 33.4% and 2.4% from IMRT and protons,
      respectively. Dose to 50% of the heart volume was reduced from 72.2% for
      conventional X-rays to 29.5% for IMRT and 0.5% for protons. Long-term toxicity
      with emphasis on hearing and endocrine and cardiac function should be
      substantially improved secondary to nontarget tissue sparing achieved with
      protons. CONCLUSION: The present study clearly demonstrates the advantage of
      conformal radiation methods for the treatment of posterior fossa and spinal
      column in children with medulloblastoma, when compared to conventional X-rays. Of
      the two conformal treatment methods evaluated, protons were found to be superior
      to IMRT.

PMID- 14967428
TI  - Toxicity after three-dimensional radiotherapy for prostate cancer with RTOG 9406
      dose level IV.
AB  - PURPOSE: This is the first report of the toxicity outcomes using dose level IV
      (74 Gy) on Radiation Therapy Oncology Group (RTOG) study 9406 for Stage T1-T2
      prostate adenocarcinoma. METHODS AND MATERIALS: A total of 262 patients were
      entered in this cooperative group, Phase I-II, dose-escalation trial of three
      dimensional conformal radiotherapy for localized prostate carcinoma treated to a
      dose of 74 Gy (Level IV); 256 patients were analyzable for toxicity. A minimal
      dose of 2 Gy/fraction was prescribed to the planning target volume (PTV).
      Patients were stratified according to the risk of seminal vesicle invasion on the
      basis of the Gleason score and presenting prostate-specific antigen level. Group
      1 patients had clinical Stage T1-T2 tumors with a seminal vesicle invasion risk
      of <15%. Group 2 patients had clinical Stage T1-T2 tumors with a seminal vesicle
      invasion risk of >/=15%. Patients in Group 1 were prescribed 74 Gy to a prostate
      PTV. Patients in Group 2 were prescribed 54 Gy to the prostate and seminal
      vesicles (PTV1) followed by a boost to the prostate only (PTV2) to 74 Gy. PTV
      margins between 5 and 10 mm were required. Elective pelvic radiotherapy was not
      used. The frequency of late effects of Grade 3 or greater was compared with that
      for a similar group of patients treated in RTOG studies 7506 and 7706, with
      length of follow-up adjustments made for the interval from therapy completion. A
      second comparison was made with 206 patients treated to dose level II (73.8 Gy in
      1.8-Gy fractions) to see whether the fraction size affected toxicity. RESULTS:
      The average months at risk for late Grade 3+ toxicity after therapy completion
      were 28.9 and 23.9 months for Group 1 and 2, respectively. Acute toxicity at dose
      level IV (74 Gy) was remarkably low, with Grade 3 acute effects reported in only
      1% of Group 1 and 3% of Group 2 patients. No Grade 4 or 5 acute toxicities were
      reported. Late toxicity continued to be low compared with RTOG historical
      controls. One patient in Group 1 and 4 patients in Group 2 experienced Grade 3
      bladder toxicity. Two patients in Group 2 experienced Grade 3 bowel toxicity. No
      Grade 4 or 5 late effects were reported. The rate of late Grade 2 toxicity (any
      type) was 23% and 16% in Group 1 and 2, respectively. The observed rate of Grade
      3 or greater late effects for Group 1 (1 case) was significantly lower (p
      <0.0001) than the 18.5 cases that would have been expected from the historical
      control data. The observed rate for Group 2 (6 cases) was also significantly
      lower (p = 0.0009) than the 21.3 cases expected. No statistically significant
      difference was noted in the rate of acute or late toxicity in patients who were
      treated to 73.8 Gy at 1.8 Gy/fraction or 74 Gy at 2.0 Gy/fraction. Patients
      treated with the larger 2.0-Gy fractions tended to have more Grade 3 or greater
      toxicity than patients treated with 1.8-Gy fractions (2% vs. 1%, p = 0.09). The
      results after the longer follow-up with dose level II suggest these differences
      may increase with additional follow-up. CONCLUSION: Tolerance to three
      dimensional conformal radiotherapy with 74 Gy in 2-Gy fractions remains better
      than expected compared with historical controls. The magnitude of any effect from
      fraction size requires additional follow-up.

PMID- 14967429
TI  - Intensity-modulated radiotherapy with MRI simulation to reduce doses received by
      erectile tissue during prostate cancer treatment.
AB  - PURPOSE: The radiation doses received by erectile tissue may contribute to
      erectile dysfunction after treatment of prostate cancer. This is the first
      description of the ability to limit the dose received by the penile bulb (PB) and
      corporal bodies (CB) using intensity-modulated radiotherapy (IMRT). METHODS AND
      MATERIALS: Twenty-three patients with palpation Stage T1c-T2bN0M0 prostate cancer
      received IMRT alone. The dose prescribed to the planning target volume was 74-78
      Gy. All patients underwent CT and MRI simulation to define the target and normal
      structures. Three plans with identical beam arrangements and energy were
      generated for each patient, with varying dose constraints for the PB and CB: no
      dose constraint, intermediate-dose constraint (20 Gy and 15 Gy, respectively) and
      low-dose constraint (15 Gy and 7 Gy, respectively). All plans were normalized,
      such that 95% of the planning target volume received at least 100% of the
      prescribed dose. For each plan, the ability to meet prostate dose homogeneity
      criteria (PHC; prostate maximal dose </=120% prescribed dose) and rectal
      tolerance dose-volume histogram criteria (RTC; </=35% and </=17% of rectal volume
      received 40 Gy and 65 Gy, respectively) was determined. The D(90), V(50), and
      V(75) were determined for both PB and the CB, where D(i) was the dose received by
      i% of the target volume and V(i) was the target volume receiving i% of the
      prescribed dose. RESULTS: The median PB D(90), V(50), and V(75) for the plans
      with no dose, intermediate-dose, and low-dose constraints was 20.8 Gy, 33.8%, and
      9.9%; 8.0 Gy, 1.7%, and 0%; and 7.1 Gy, 0.1%, and 0%, respectively. The median CB
      D(90), V(50), and V(75) for plans with no dose, intermediate-dose, and low-dose
      constraints was 10.2 Gy, 3.8%, and 0%; 6.0 Gy, 0%, and 0%; and 4.9 Gy, 0%, and
      0%, respectively. Overall differences in the D(90), V(50), and V(75) among the
      groups were significant for both the PB and the CB (p <0.0001). All plans with no
      dose constraint met the PHC and RTC. Twenty plans with an intermediate-dose
      constraint met the PHC and 21 met the RTC. Eighteen plans with a low-dose
      constraint met the PHC and 19 met the RTC. No statistically significant
      difference was found in the number of beam segments for the three groups (median
      of 51, 55, and 53; p = 0.8). CONCLUSION: In the vast majority of cases, it is
      possible to limit the dose to erectile tissue with IMRT, usually by >/=50%
      without significantly compromising the PHC, RTC, or treatment duration. A Phase
      III randomized trial has been designed to test the clinical significance of the
      erectile tissue-sparing technique described here.

PMID- 14967430
TI  - Polarographic electrode study of tumor oxygenation in clinically localized
      prostate cancer.
AB  - PURPOSE: To describe the oxygenation of clinically localized prostate cancer.
      METHODS AND MATERIALS: Intraprostatic oxygen tension was measured using the
      Eppendorf electrode in 55 unanesthetized men with localized prostate cancer
      before radiotherapy. Measurements were made along two tracks through regions of
      suspected tumor in the prostate, and core needle biopsies were then obtained from
      the same regions. RESULTS: The median pO(2) ranged from 0.2 to 57.3 mm Hg, and
      the grand median pO(2) was 4.5 mm Hg. The percentage of oxygen readings <5 mm Hg
      (HP(5)) ranged from 0% to 100% (median 60%). The track 1 oxygen readings were
      greater than those from track 2. Statistically significant heterogeneity was
      found in the individual oxygen readings: the between- and within-tumor components
      accounted for 32% and 68% of the total variability, respectively. However, the
      between-tumor variability in HP(5) significantly exceeded the within-tumor
      variability (61% vs. 39%). No association was found between oxygen values and
      clinical factors, including age, T stage, Gleason score, prostate-specific
      antigen level, hemoglobin concentration, or prior hormonal treatment. No
      difference was noted in the oxygenation between regions of tumor and normal
      prostate tissue, as determined from the core biopsies. CONCLUSION: Localized
      prostate cancer is characterized by marked hypoxia and significant heterogeneity
      in oxygenation, similar to other human tumors. The normal prostate may contain
      regions of low oxygen concentration. HP(5), as determined in this study, should
      adequately discriminate among patients with prostate cancer and allow the
      independent prognostic significance of oxygenation to be evaluated once the study
      matures.

PMID- 14967431
TI  - Increased IL-6 and TGF-beta1 concentrations in bronchoalveolar lavage fluid
      associated with thoracic radiotherapy.
AB  - PURPOSE: To assess, in lung cancer patients, the effects of thoracic radiotherapy
      (RT) on the concentrations of transforming growth factor-beta(1) (TGF-beta(1))
      and interleukin-6 (IL-6) in the bronchoalveolar lavage (BAL) fluid. METHODS AND
      MATERIALS: Eleven patients with lung cancer requiring RT as part of their
      treatment were studied. BAL was performed bilaterally before, during, and 1, 3,
      and 6 months after RT. Before each BAL session, the patient's status was assessed
      clinically using pulmonary function tests and an adapted late effects on normal
      tissue-subjective, objective, management, analytic (LENT-SOMA) scale, including
      subjective and objective alterations. The National Cancer Institute Common
      Toxicity Criteria were used to grade pneumonitis. The TGF-beta(1) and IL-6 levels
      in the BAL fluid were determined using the Easia kit. RESULTS: The TGF-beta(1)
      and IL-6 concentrations in the BAL fluid recovered from the irradiated areas were
      significantly increased by thoracic RT. The increase in TGF-beta(1) levels tended
      to be greater in the group of patients who developed severe pneumonitis. In the
      BAL fluid from the nonirradiated areas, the TGF-beta(1) and IL-6 concentrations
      remained unchanged. CONCLUSION: The observed increase in TGF-beta(1) and IL-6
      concentrations in the BAL fluid recovered from the irradiated lung areas
      demonstrated that these cytokines may contribute to the process leading to a
      radiation response in human lung tissue.

PMID- 14967432
TI  - Concurrent chemoradiotherapy with gemcitabine and cisplatin after incomplete (R1)
      resection of locally advanced pancreatic carcinoma.
AB  - PURPOSE: To analyze, in a prospective clinical trial, the efficacy and toxicity
      of concurrent radiotherapy and chemotherapy with gemcitabine and cisplatin in
      patients with incompletely (R1) resected pancreatic cancer. METHODS AND
      MATERIALS: Between 2000 and 2002, a total of 30 pancreatic cancer patients were
      treated. Radiotherapy was performed in 15 patients up to a total dose of 45.0 Gy.
      An additional 15 patients received a total dose of 50.0 Gy according to the
      International Commission on Radiation Units and Measurements (ICRU) Report 50
      reference point (equivalent to 45.0 Gy at the isodose, including 90% covering the
      former tumor area and local lymph nodes). Concurrent with radiotherapy, four
      applications of gemcitabine (300 mg/m(2)) and cisplatin (30 mg/m(2)) were
      administered. After chemoradiotherapy, patients received four additional courses
      of gemcitabine (1000 mg/m(2)) and cisplatin (50 mg/m(2)) on Days 1 and 15 in a 4
      week cycle. RESULTS: The median progression-free survival was 10.6 months, and
      the median overall survival was 22.8 months. The 1-, 2-, and 3-year survival rate
      was 81%, 43%, and 26%, respectively. After completion of chemoradiotherapy,
      distant metastasis was observed in 14 patients during a median follow-up of 15.0
      months (range, 4.6-30.0). One patient developed both local recurrence and distant
      metastases. Hematologic toxicities were the most prominent side effects
      (leukopenia Grade 3 and 4 in 53% and 7% and thrombocytopenia Grade 3 and 4 in 33%
      and 7% of patients, respectively). Grade 3 and 4 GI toxicity was not observed.
      CONCLUSION: Postoperative chemoradiotherapy with gemcitabine and cisplatin after
      incomplete (R1) resection of pancreatic carcinoma is safe and feasible. A
      prolonged progression-free survival suggests high local efficacy, translating
      into a benefit of overall survival. On the basis of the favorable outcome of
      patients receiving gemcitabine/cisplatin-based chemoradiotherapy, testing this
      combined treatment strategy appears warranted in a comparative trial.

PMID- 14967433
TI  - Extracapsular spread of nodal metastasis as a prognostic factor in rectal cancer.
AB  - PURPOSE: To evaluate the prognostic value of lymph node metastasis with
      extracapsular extension (ECE) for local control and metastasis-free survival in
      rectal cancer. METHODS AND MATERIALS: A total of 145 rectal cancer patients were
      treated with surgery and postoperative radiochemotherapy. Patients were grouped
      according to nodal status (node negative, n = 49; node positive without ECE, n =
      64; node positive with ECE, n = 32). In addition, well-known prognostic factors
      such as International Union Against Cancer (UICC) stage, T and N stage, presence
      of lymphangiosis, and grade were assessed. The end points were analyzed by the
      Kaplan-Meier method, and prognostic factors were compared in a Cox regression
      model. RESULTS: Of the entire group, the actuarial 5-year local control and
      distant metastasis-free survival rate was 85% and 66%, respectively, after a
      median follow-up of 47 months (range, 14-104). Patients with ECE of lymph node
      metastasis had an impaired 5-year local control rate (58%) compared with node
      negative (83%) and node-positive without extracapsular involvement patients (87%,
      p = 0.041). Metastasis-free survival also differed for the three groups, with a
      rate of 40% for those with extracapsular involvement, 54% for those without ECE,
      and 78% for node-negative patients (p <0.0001). The impact of ECE on local
      control was confirmed in the regression model (risk ratio [RR] 1.6, 95%
      confidence interval [CI] 1.01-2.7, p = 0.044). T stage was only of borderline
      significance (RR 2.4, 95% CI 1.0-5.7, p = 0.052). However, only UICC stage (RR
      5.1, 95% CI 2.0-13.1, p <0.001) and the presence of lymphangiosis (RR 2.8, 95% CI
      1.4-5.3, p = 0.002) were of independent prognostic value for distant metastasis.
      CONCLUSION: ECE of node metastasis is connected with a substantial decline in
      local control. The frequency of distant metastasis is increased in this patient
      group as well, but stage and lymphangiosis are the independent factors for
      assessment of a patient's risk of systemic spread.

PMID- 14967434
TI  - A Phase I trial of preoperative eniluracil plus 5-fluorouracil and radiation for
      locally advanced or unresectable adenocarcinoma of the rectum and colon.
AB  - PURPOSE: Eniluracil, an effective inactivator of dihydropyrimidine dehydrogenase,
      allows for oral dosing of 5-fluorouracil (5-FU), which avoids the morbidity of
      continuous infusion 5-FU. We addressed the safety of oral eniluracil and 5-FU
      combined with preoperative radiotherapy and determined the recommended Phase II
      dose and dose-limiting toxicity in patients with locally advanced rectal and
      colon cancer. METHODS AND MATERIALS: Patients with TNM Stage II or III rectal
      cancer and residual or recurrent colon cancer received eniluracil (starting at
      6.0 mg/m(2) every 12 h) and 5-FU (starting at 0.6 mg/m(2) every 12 h). Eniluracil
      and 5-FU were given with a 5-week course of preoperative radiotherapy of 4500
      cGy, with a possible 540-cGy boost. Surgery was performed approximately 4 weeks
      after completion of chemoradiotherapy. RESULTS: Twenty-two patients were
      enrolled; 1 patient was withdrawn owing to noncompliance. Chemotherapy was
      completed in all patients; radiotherapy was completed in 20 patients. The
      recommended Phase II dose of eniluracil and 5-FU was 8 mg/m(2) every 12 h and 0.8
      mg/m(2) every 12 h, respectively. Diarrhea was the dose-limiting toxicity. Eleven
      of the 17 patients with primary rectal cancer underwent a sphincter-sparing
      procedure. One patient had a pathologic complete response. CONCLUSION:
      Preoperative chemoradiotherapy with oral eniluracil and 5-FU is feasible and well
      tolerated. Additional investigation is warranted.

PMID- 14967435
TI  - Malignant mixed Mullerian tumors of the uterus: analysis of patterns of failure,
      prognostic factors, and treatment outcome.
AB  - PURPOSE: To determine the survival outcomes, prognostic factors, and patterns of
      failure in patients with malignant mixed Mullerian tumor (MMMT) of the uterus.
      METHODS AND MATERIALS: Between 1954 and 1998, 300 patients with clinical Stage I
      III MMMT of the uterus were treated with curative intent at The University of
      Texas M. D. Anderson Cancer Center. Their hospital records were reviewed to
      obtain patient and tumor characteristics; details of surgery, radiotherapy (RT),
      and chemotherapy; and long-term outcome. Surviving patients were followed for a
      median of 109 months (range 15-138). Survival rates were calculated using the
      Kaplan-Meier method, with differences assessed by log-rank tests. RESULTS: Of the
      300 patients, 113 (38%) were treated with surgery alone, 160 (53%) with surgery
      plus adjuvant EBRT or ICRT, and 27 (9%) with RT alone. Forty-eight patients
      received adjuvant chemotherapy. At 5 years, the overall rates of survival and
      cause-specific survival were 31% and 33%, respectively. Women who were
      postmenopausal or had a history of prior pelvic RT, pain at presentation,
      clinical Stage II-III disease, uterine enlargement (>/=12 weeks), or an abnormal
      Papanicolaou smear finding had a significantly poorer prognosis than the other
      patients in the series. Of the 273 patients who underwent surgery, those who had
      positive abdominal washings, uterine length >10 cm, or extrauterine spread of
      disease to the cervix, adnexa, or peritoneum had a significantly worse prognosis
      than the other patients. Factors found on multivariate analysis to have an
      independent adverse influence on cause-specific survival included postmenopausal
      status (p = 0.0007, relative risk [RR] 3.3), uterine length >10 cm (p = 0.0001,
      RR 2.2), cervical involvement (p = 0.002, RR 1.8), and peritoneal involvement (p
      = 0.0001, RR 4.3). At 5 years, the rates of pelvic and distant disease recurrence
      for the entire group of 300 patients were 38% and 57%, respectively. The most
      common site of distant recurrence was the peritoneal cavity. Patients treated
      with pelvic RT had a lower rate of pelvic recurrence than patients treated with
      surgery alone (28% vs. 48%, p = 0.0002), but the overall survival rates (36% vs.
      27%, p = 0.10) and distant metastasis rates (57% vs. 54%, p = 0.96) were not
      significantly different. However, patients treated with pelvic RT had a longer
      mean time to any distant relapse (17.3 vs. 7.0 months, p = 0.001) than patients
      treated with surgery alone. The use of adjuvant chemotherapy did not correlate
      with the survival rate or rate of distant metastasis. CONCLUSION: Adjuvant pelvic
      RT decreased the risk of pelvic recurrence and may delay the appearance of
      distant metastases after hysterectomy for MMMT. However, the survival rates
      remain poor because of a high rate of distant recurrence. As more effective
      systemic chemotherapy is developed to control microscopic distant disease, the
      role of RT in controlling locoregional disease in the pelvis and abdomen may
      become more important. Future research should consider programs that integrate
      surgery, RT, and chemotherapy to maximize the probability of cure.

PMID- 14967436
TI  - A positive margin is not always an indication for radiotherapy after mastectomy
      in early breast cancer.
AB  - OBJECTIVE: Postoperative radiotherapy is frequently employed among breast cancer
      patients with positive surgical margins after mastectomy but there is little
      evidence to support this practice. This study examined relapse and survival among
      women with node-negative breast cancer and positive surgical margins after
      mastectomy. METHODS: Among 2570 women diagnosed between 1989 and 1998 and
      referred to the British Columbia Cancer Agency with pathologic (p)T1-2, pN0
      invasive breast cancer treated with mastectomy, 94 had positive surgical margins
      and formed the study cohort. Women with more established indications for
      postmastectomy radiotherapy (PMRT) including T3-4 tumors or node-positive disease
      were excluded. Demographic, tumor, and treatment factors; relapse patterns; and
      Kaplan-Meier 8-year locoregional relapse-free, breast cancer-specific, and
      overall survival rates were compared between women who were treated with (n = 41)
      and without (n = 53) PMRT. RESULTS: Median follow-up time was 7.7 years. The
      distributions of age, histologic grade, lymphovascular invasion (LVI), estrogen
      receptor status, and number of axillary nodes removed were similar between the
      two treatment groups. Six local chest wall recurrences (6.4%), 4 regional
      recurrences (4.3%), and 11 distant recurrences (11.7%) were identified. Local
      relapse rates were 2.4% vs. 9.4% (p = 0.23), and regional relapse rates were 2.4%
      vs. 5.7% (p = 0.63), with and without PMRT, respectively. Trends for higher
      cumulative locoregional relapse (LRR) rates without PMRT were identified in the
      presence of age <==50 years (LRR 20% without vs. 0% with PMRT), T2 tumor size
      (19.2% vs. 6.9%), grade III disease (23.1% vs. 6.7%), and LVI (16.7% vs. 9.1%).
      Statistical significance was not demonstrated in these differences (p > 0.10),
      possibly because of the small number of events. In patients with age >50 years,
      T1 tumors, grade I/II disease, and absence of LVI, no locoregional relapse
      occurred even with positive margins. PMRT did not improve distant relapse, 8-year
      breast cancer-specific and overall survival rates. CONCLUSION: This study
      suggests that not all patients with node-negative breast cancer with positive
      margins after mastectomy require radiotherapy. Locoregional failure rates
      approximating 20% were observed in women with positive margins plus at least one
      of the following factors: age <==50 years, T2 tumor size, grade III histology, or
      LVI. The absolute and relative improvements in locoregional control with
      radiotherapy in these situations support the judicious, but not routine, use of
      PMRT for positive margins after mastectomy in patients with node-negative breast
      cancer.

PMID- 14967437
TI  - Initiation of a teleradiotherapeutic network for patients in German lymphoma
      studies.
AB  - PURPOSE: Deviations of radiation treatment portals and dose from prospective
      treatment plans are unfavorable prognostic factors for lymphoma patients.
      Therefore, an extensive radiotherapy quality assurance program is used in the
      ongoing German lymphoma studies. The introduction of teleradiotherapy offered the
      opportunity to optimize and simplify the workflow of these quality assurance
      programs. The purpose of this report was to evaluate the feasibility of
      teleradiotherapy and to describe our experiences with these innovative tools.
      METHODS AND MATERIALS: During this pilot phase, five radiotherapy centers were
      equipped with the hardware and software that guarantees a rapid and high-quality
      transfer of imaging data, as well as real-time teleconferences. The workstation
      consists of standard PCs with Windows NT as the operating system and the
      commercial telemedicine software Hipax. RESULTS: As a first step, imaging
      communication between the radiotherapy reference centers in Cologne and
      Homburg/Saar was established. Subsequently, three additional radiotherapy
      departments (Universities of Berlin, Munster, and Munich) with large numbers of
      lymphoma patients were connected. Other study centers delivered digital imaging
      on mobile data carriers or via an Integrated Services Digital Network point-to
      point connection. Communication units were completed for interactive
      teleconferences. A facility for central online documentation was installed.
      Telemedical functions were integrated into the ongoing radiotherapy quality
      assurance program. Since the introduction of a teleradiotherapeutic workstation
      in the radiotherapy reference center in Cologne in January 2001, the images of
      10% (n = 228 patients) of all reviewed cases of the ongoing Hodgkin's disease 10
      12 trials were delivered digitally. The amount of digitally available imaging is
      continuously increasing. CONCLUSION: The introduction of teleradiotherapy
      improved the dialog between the radiotherapy reference centers and study centers
      and thus contributed toward high radiotherapy quality for lymphoma patients in
      Germany.

PMID- 14967438
TI  - Renal insufficiency in patients with hematologic malignancies undergoing total
      body irradiation and bone marrow transplantation: a prospective assessment.
AB  - PURPOSE: Patients with malignant hematologic disorders undergoing bone marrow
      transplantation (BMT) may develop renal insufficiency. A study was undertaken to
      assess prospectively the subclinical renal function changes with radioisotopic
      methods in patients undergoing BMT for hematologic malignancies. METHODS AND
      MATERIALS: We studied 71 patients with normal renal function undergoing BMT for
      various hematologic malignancies, mostly leukemias. Conditioning included
      chemotherapy and 12 Gy (45 patients) or 13.5 Gy (26 patients) fractionated total
      body irradiation (TBI). In 21 patients receiving 12 Gy TBI, the kidney dose was
      limited to 10 Gy using partial transmission blocks fabricated after renal
      opacification with nonionic, hypo-osmolar contrast medium. The glomerular
      filtration rate (GFR) and effective renal plasmatic flow (ERPF) were determined
      radioisotopically before conditioning and at 4, 12, and 18 months, using (51)Cr
      ethylene-diamine-tetra-acetic acid and (131)I ortho-iodo-hippurate, respectively.
      Renal insufficiency was defined as a decrease of >/=30% in GFR or ERPF compared
      with the baseline values. The potential influence of patient- and treatment
      related variables on renal dysfunction was assessed. RESULTS: At 4 (early) and 12
      18 (late) months, a >/=30% GFR drop was observed in 54% and 49% of patients and a
      >/=30% ERPF drop in 44% and 34% of patients, respectively. After stepwise
      logistic analysis, a GFR reduction at 4 months correlated significantly with age
      (<40 years old, worse), TBI using kidney blocks (partial kidney shielding to 10
      Gy was associated with a higher rate of renal dysfunction at 4 months compared
      with the full TBI dose), and days of aminoglycoside/vancomycin use. An ERPF drop
      at 4 months was independently related with the days of amphotericin use and days
      of prostaglandin E(1) use (prophylaxis against hepatic venoocclusive disease). A
      GFR and ERPF reduction at 12-18 months correlated with days of amphotericin use
      and days of prostaglandin E(1) use, respectively. CONCLUSION: Early post-BMT
      renal dysfunction is associated with the administration of potentially
      nephrotoxic drugs. An inverse correlation with the prescribed TBI dose was
      observed; patients whose kidneys received 10 Gy through the use of partial
      shielding blocks had significantly greater renal dysfunction at 4 months. The
      administration of potentially nephrotoxic contrast agents used in radiotherapy
      treatment planning may be responsible for the latter observation. Prostaglandin
      E(1) use correlated with a significant reduction in ERPF at both 4 and 12-18
      months.

PMID- 14967439
TI  - Successful reduction of in-stent restenosis in long lesions using beta-radiation-
      subanalysis from the RENO registry.
AB  - PURPOSE: Long lesions remain a challenging task in interventional cardiology,
      with a high propensity of restenosis, especially within the stented segment.
      Although intracoronary gamma-radiation has been proved to reduce diffuse in-stent
      restenosis in long lesions, such an effect remains to be determined using beta
      radiation. METHODS AND MATERIALS: Of 1098 consecutive patients at 46 European
      centers treated with localized beta-radiation ((90)Sr, Novoste Beta-Cath System),
      139 patients (mean age 61.5 +/- 10.7 years, 84% male, 22% with diabetes mellitus)
      with lesions treated using a >40-mm source length underwent radiation using a
      single 60-mm source train (34%) or a stepping/pullback procedure with a 30-mm
      (12%) or 40-mm (87%) source length after conventional interventional procedures.
      The mean lesion length was 35.3 +/- 17.9 mm. RESULTS: Technical success was
      achieved in 96% of cases. Geographic miss was noted in 9 patients (6.5%). The
      reference (placebo) group was obtained from the Washington Hospital Center for In
      Stent Restenosis Trial (WRIST) and the WRIST Trial for long lesions (LONG WRIST)
      studies by selecting the cases (94 patients) that required a dummy source length
      >/=13 seeds (or >51 mm in length). Statistically significant improvement was
      noted in late angiographic restenosis (34.7% vs. 76.5%, p <0.0001), target vessel
      revascularization (14.9% vs. 60.6), and major adverse cardiac events (i.e.,
      death, myocardial infarction, or total vessel revascularization) (17.9% vs.
      64.9%, p <0.0001) at 6 months in reference to the nonradiation group. CONCLUSION:
      This subanalysis from the Radiation in Europe with Novoste study confirms the
      safety and efficacy of beta-radiation combined with conventional interventional
      procedures in patients with diffuse, long, in-stent restenosis

PMID- 14967440
TI  - Radiotherapy in painful heel spurs (plantar fasciitis)--results of a national
      patterns of care study.
AB  - PURPOSE: After a general patterns of care study, the German Cooperative Group on
      Radiotherapy for Benign Diseases conducted a multicenter cohort study to analyze
      radiotherapy (RT) in painful heel spur syndrome (HSS). METHODS AND MATERIALS: In
      2001, a patterns of care study was conducted in all German RT institutions using
      a standardized structured questionnaire. Patient accrual, patient number,
      pretreatment, pain record, treatment indications, RT technique, and target volume
      concepts for painful HSS were assessed. In addition, the functional and
      subjective outcomes were evaluated. RESULTS: Of the institutions, 146 (79.3%)
      returned the questionnaire: 10 (6.8%) reported no clinical experience with RT for
      HSS, and 136 (93.2%) treated 3621 patients annually, a median of 23
      cases/institution. The indications for treatment were chronic or therapy
      refractory pain. The total dose ranged between 2.5 and 18.75 Gy (median 6), and
      single fractions ranged between 0.3 and 1. 5 Gy (median 1). Of the responding
      institutions, 44.9% applied two fractions and 37.5% three fractions weekly. RT
      was delivered with orthovoltage units (38.2%), linear accelerators (53.7%),
      (60)Co units (5.1%), or other treatment units (3%). Seventy-six institutions
      presented their retrospective clinical evaluation in a total of 7947 patients.
      Pain reduction for at least 3 months was reported in 70%, and persistent pain
      reduction was reported in 65% of the treated patients. In 19 institutions, a
      second RT series was applied for inadequate pain response or early pain
      recurrence. No radiogenic acute or chronic side effects were observed.
      CONCLUSION: The study comprised the largest number of cases reported of RT for
      painful HSS. Despite variations in the daily RT practice, this national patterns
      of care study represents a very large number of painful and refractory HSS cases
      that were treated effectively with RT.

PMID- 14967441
TI  - Broad spectrum receptor tyrosine kinase inhibitor, SU6668, sensitizes radiation
      via targeting survival pathway of vascular endothelium.
AB  - PURPOSE: Recent studies have demonstrated radiosensitization by inhibiting
      receptor tyrosine kinases (RTKs). Irradiation activates RTKs and their downstream
      prosurvival molecule, Akt. In this study, we investigated the mechanism by which
      SU6668, an inhibitor of RTKs involved in angiogenic pathways, enhances effects of
      irradiation. METHODS AND MATERIALS: Western blots were used to determine Akt
      phosphorylation. Clonogenic assays were performed to determine endothelial
      survival after combination of SU6668 and irradiation. This combination therapy
      was also tested in mouse models with Lewis lung carcinoma or glioblastoma
      multiforme (GL261) for inhibition of tumor growth and tumor vasculature by
      examining tumor volume, tumor vascular window, and blood flow. RESULTS: We found
      that SU6668 inhibited the Akt activation inducible by irradiation. Clonogenic
      survival of endothelial cells was decreased after the combined therapy compared
      with radiotherapy alone. In vivo studies demonstrated reduction of tumor
      vasculature and blood flow. In addition, 21 Gy in 7 fractions given concurrently
      with SU6668 resulted in tumor growth delay compared to either treatment alone.
      CONCLUSION: These data suggest that the combination therapy was more effective in
      destroying tumor vasculature than either treatment alone. SU6668 augments tumor
      suppressive effects of radiotherapy in Lewis lung carcinoma and GL261 xenographs,
      possibly through reducing the survival of tumor endothelium.

PMID- 14967442
TI  - Ascorbate as a "redox sensor" and protector against irradiation-induced oxidative
      stress in 32D CL 3 hematopoietic cells and subclones overexpressing human
      manganese superoxide dismutase.
AB  - PURPOSE: To determine whether increased expression of manganese superoxide
      dismutase (MnSOD) protects cells from irradiation by preventing the production of
      reactive oxygen species (ROS), a new approach to detecting free radical
      intermediates using ascorbate as an endogenous spin trap was used. MATERIALS AND
      METHODS: Cells from the 32D cl 3 hematopoietic cell line or a subclone
      overexpressing MnSOD (2C6) were incubated with dehydroascorbate for 30 min and
      irradiated to doses from 0 to 50 Gy. Radical intermediates reacting with spin
      traps or ascorbate were measured by electron spin resonance spectroscopy. Results
      were compared to irradiation-induced changes in thiol levels, irradiation
      survival curves, and accumulation of 8-OHdG as a measurement of DNA oxidative
      damage. RESULTS: Manganese superoxide dismutase-overexpressing 2C6 cells
      maintained higher levels of ascorbate (5.4 +/- 0.5 and 2.6 +/- 0.5 nmol/10(6)
      cells, respectively) and thiols (14.0 +/- 0.1 and 11.1 +/- 0.2 nmol/10(6) cells)
      compared to 32D cl 3 parent cells. Cells overexpressing MnSOD produced lower
      levels of ROS than did the parental 32D cl 3 cells, as evidenced by lower
      expenditure of ascorbate and GSH after irradiation. Increased ascorbate levels
      protected both 32D cl 3 and 2C6 cells from irradiation killing, as demonstrated
      by an increased shoulder on survival curves and decreased DNA 8-OHdG
      accumulation. CONCLUSIONS: Manganese superoxide dismutase overexpression protects
      2C6 cells from irradiation damage by scavenging ROS that readily interact with
      major endogenous antioxidants--ascorbate and GSH--in nontransfected hematopoietic
      32D cl 3 cells.

PMID- 14967443
TI  - Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is
      immune mediated.
AB  - PURPOSE: Ionizing radiation can reduce tumor growth outside the field of
      radiation, known as the abscopal effect. Although it has been reported in
      multiple malignancies, the abscopal effect remains a rare and poorly understood
      event. Ionizing radiation generates inflammatory signals and, in principle, could
      provide both tumor-specific antigens from dying cells and maturation stimuli that
      are necessary for dendritic cells' activation of tumor-specific T cells. We
      therefore tested the hypothesis that the abscopal effect elicited by radiation is
      immune mediated. This was directly tested by enhancing the number of available
      dendritic cells using the growth factor Flt3-Ligand (Flt3-L). METHODS AND
      MATERIALS: Mice bearing a syngeneic mammary carcinoma, 67NR, in both flanks were
      treated with Flt3-L daily for 10 days after local radiation therapy (RT) to only
      1 of the 2 tumors at a single dose of 2 or 6 Gy. The second nonirradiated tumor
      was used as indicator of the abscopal effect. Data were analyzed using repeated
      measures regression. RESULTS: RT alone led to growth delay exclusively of the
      irradiated 67NR tumor, as expected. Surprisingly, growth of the nonirradiated
      tumor was also impaired by the combination of RT and Flt3-L. As control, Flt3-L
      had no effect without RT. Importantly, the abscopal effect was shown to be tumor
      specific, because growth of a nonirradiated A20 lymphoma in the same mice
      containing a treated 67NR tumor was not affected. Moreover, no growth delay of
      nonirradiated 67NR tumors was observed when T cell deficient (nude) mice were
      treated with RT plus Flt3-L. CONCLUSIONS: These results demonstrate that the
      abscopal effect is in part immune mediated and that T cells are required to
      mediate distant tumor inhibition induced by radiation.

PMID- 14967444
TI  - A simple alpha/beta-independent method to derive fully isoeffective schedules
      following changes in dose per fraction.
AB  - PURPOSE: Dosimetric errors in delivering the prescribed dose per fraction made
      early in a treatment can be corrected by modifying the dose per fraction and
      total dose given subsequently to discovery of the error, using the linear
      quadratic model to calculate the correcting doses which should be completed
      within the same overall time as originally prescribed. This study shows how these
      calculations can be carried out independently of any alpha/beta ratios to bring
      the treatment back exactly to planned tolerance simultaneously for all tissues
      and tumor involved. METHODS: Planned treatment is defined as p Gy per fraction to
      a total dose P Gy; the initial error is e Gy per fraction given to a total of E
      Gy. The linear-quadratic formula is assumed to describe all isoeffect
      relationships between total dose and dose per fraction. RESULTS AND CONCLUSION:
      An exact solution is found that describes a compensating dose of d Gy per
      fraction to a total of D Gy. The formulae are: D = P-E d = Pp-Ee/P-E. Thus the
      total dose for the complete treatment (error plus compensation) remains as
      originally prescribed, with hyperfractionation being used to correct an initial
      hypofractionation error and hypofractionation being used to correct an initial
      hyperfractionation error. Incomplete repair is shown to perturb this exact
      solution. Thus compensating treatments calculated with these formulae should not
      be scheduled in such a manner that would introduce incomplete repair.

PMID- 14967445
TI  - The delivery of IMRT with a single physical modulator for multiple fields: a
      feasibility study for paranasal sinus cancer.
AB  - PURPOSE: This study describes a new intensity-modulated radiation therapy (IMRT)
      delivery method that utilizes a single modulator to deliver multiple fields
      ("multifield modulator"). This technique reduces the treatment time and
      manufacturing costs typically associated with modulator-IMRT. Technical
      feasibility was evaluated for treating paranasal sinus cancers. METHODS AND
      MATERIALS: Technical feasibility was measured by three criteria: The dose
      distributions of the multifield modulator-IMRT plans should offer improvements
      over those produced by 3D conformal plans and be equivalent to those of step-and
      shoot multileaf collimator (MLC) IMRT plans, the manufactured modulators should
      meet quality assurance specifications, and the effort required to use this
      technology should not substantially exceed the effort required for current IMRT
      practice. Seven paranasal cancer cases were examined. The Wilcoxon signed rank
      test was used for statistical analysis. RESULTS: Multifield modulator-IMRT plans
      can improve target coverage while reducing critical structure doses compared to
      3D conformal plans. Multifield modulator-IMRT plans are at least equivalent to
      the corresponding step-and-shoot MLC-IMRT plans. Multifield modulators can be
      constructed to meet design specifications in quality assurance tests. The time
      required for manufacturing, quality assurance, and treatment delivery using
      multifield modulators was measured and found to be only slightly greater than
      that for current IMRT treatment methods. CONCLUSIONS: IMRT treatments using
      multifield modulators for paranasal sinus tumors are feasible. Clinics may find
      it worthwhile to commit the minimal extra time for quality assurance and
      treatment to benefit from the improved dose distribution and lack of interplay
      between MLC leaf motion and internal target motion.

PMID- 14967446
TI  - In vivo detection of an 125I seed located in the intracardiac region after
      prostate permanent brachytherapy.
AB  - PURPOSE: The purpose of this investigation is to determine the mechanism of seed
      migration after prostate implant and to develop procedures to minimize the risk
      of seed migration. METHODS AND MATERIALS: Radioactivity survey of prostate cancer
      patients after permanent brachytherapy with (125)I to detect pulmonary seed
      embolization is routinely performed using a seed migration detector. The seed
      migration detector is made from a low-energy, high-sensitivity scintillation
      survey meter by adding a single-hole collimation cap to the scintillation probe.
      If a seed migration is suspected, a pair of chest radiographs is ordered to
      document the location of the migrated seed. A comprehensive investigation is
      elicited if there are discrepancies between the seed migration detector survey
      and the radiographic examination. RESULTS: One hundred five patients have been
      surveyed, and 20 patients have demonstrated pulmonary seed embolization. In 1
      patient, the seed migration detector sensed radioactivity in the thorax, but
      repeat chest radiographic examinations failed to show a radiopaque foreign body
      in the chest cavity. Owing to the signal variation mimicking heart rate, an
      (125)I seed located in the intracardiac region was suspected. This suspicion was
      confirmed in a high-quality fluoroscopy examination. CONCLUSIONS: Seed
      embolization to the intracardiac region is rarely reported. The true rate may be
      higher, but has not been adequately documented owing to the limitation of
      diagnostic quality of chest radiographs to detect seed migration to the
      intracardiac region. The seed migration detector, on the other hand, demonstrated
      its efficacy in the detection of seed migration, particularly in the detection of
      a seed located in the intracardiac region.

PMID- 14967447
TI  - Dosimetric study of boron neutron capture therapy with borocaptate sodium
      (BSH)/lipiodol emulsion (BSH/lipiodol-BNCT) for treatment of multiple liver
      tumors.
AB  - PURPOSE: We performed a computational study to investigate the feasibility of
      borocaptate sodium (BSH)/lipiodol-boron neutron capture therapy (BSH/lipiodol
      BNCT) for multiple liver tumors using Simulation Environment for Radiotherapy
      Applications (SERA), a currently available BNCT treatment planning system.
      METHODS AND MATERIALS: Three treatment plans for BSH/lipiodol-BNCT using two or
      three epithermal neutron beams in one fraction were generated for 4 patients with
      multiple liver tumors using the SERA system. The (10)B concentrations in the
      tumor and the liver assumed in the study were 197.3 and 15.3 ppm, respectively;
      and were obtained from experimental studies in animals. The therapeutic gain
      factors for the liver tumors, defined as the minimum dose to the tumor/maximum
      dose to the liver, and the inhomogeneity index of the thermal neutron fluence for
      the whole of the liver, defined as the maximum neutron fluence - minimum neutron
      fluence/mean neutron fluence, were evaluated in each plan. RESULTS: Three
      epithermal neutron beams incident on the anterior, posterior, and right side of
      the patient can deliver the most homogeneous distribution of thermal neutron
      fluence to the whole of the liver and provide the greatest therapeutic gain
      factors for tumors in the right lobe and approximately equal therapeutic gain
      factors for tumors in the left lobe, compared with the two opposed (anterior
      posterior) and two orthogonal (anterior-right) beams. CONCLUSIONS: From a
      dosimetric viewpoint, the BSH/lipiodol-BNCT treatment plan using three epithermal
      neutron beams is the most suitable for the treatment of multiple liver tumors.

PMID- 14967448
TI  - Epidermal Growth Factor Receptor (EGFR) Inhibitors and Cancer Therapeutics.
      Proceedings of the Radiation Therapy Oncology Group Symposium. Philadelphia,
      Pennsylvania, USA. June 14, 2002.

PMID- 14967449
TI  - Targeting the EGFR in neoplasia--more questions than answers.

PMID- 14967450
TI  - Signal transduction and oncogenesis by ErbB/HER receptors.
AB  - Growth factors enable cells to escape irradiation-induced death (apoptosis). One
      important family of growth factors share an epidermal growth factor motif, and
      all bind to ErbB transmembrane receptors. In response to growth factor ligands,
      ErbB receptor tyrosine kinases induce a variety of cellular responses, including
      proliferation, differentiation and motility. Signal transduction pathways are
      initiated upon ligand-induced receptor homo- or heterodimerization and activation
      of tyrosine kinase activity. The complement of induced signaling pathways, as
      well as their magnitude and duration, determines the biological outcome of
      signaling, and in turn, is regulated by the identity of the ligand and the
      receptor composition. Recent insights into the structural basis for receptor
      dimerization, as provided by crystallographic analysis, are described, as is the
      differential activation of signaling pathways and downregulatory mechanisms.
      Further, dysregulation of the ErbB network is implicated in a variety of human
      cancers, and the nature of aberrant signaling through ErbB proteins, as well as
      current therapeutic approaches, are discussed, highlighting the role of the
      highly oncogenic ErbB-2 molecule.

PMID- 14967451
TI  - Acquired resistance to EGFR inhibitors: mechanisms and prevention strategies.
AB  - Potent and specific, or relatively specific, inhibitors of epidermal growth
      factor receptor (EGFR) signaling, including monoclonal antibodies and small
      molecular weight compounds, have been successfully developed. Both types of agent
      have been found to have significant antitumor activity, especially when used in
      combination with radio- hormone- and chemotherapy in preclinical studies. Because
      of the potentiation of the conventional drug activity in these combination
      settings, inhibitors of EGFR signaling have often been referred to as sensitizers
      for chemotherapy or radiation, as well as drug resistance reversal agents. Phase
      II clinical trials in head-and-neck as well as lung cancer suggested this concept
      of chemosensitization might translate into the clinic, but this remains to be
      definitively proven in randomized, double-blind Phase III trials. Given the
      extensive preclinical literature on EGFR blocking drugs and the advanced clinical
      development of such agents, it is surprising that the possibility of development
      of acquired resistance to the EGFR inhibitors themselves, a common clinical
      problem with virtually all other currently used anticancer drugs, remains a
      largely unexplored subject of investigation. Here we summarize some of the
      possible mechanisms that can result in acquired resistance to EGFR-targeting
      drugs. Alternative combination therapies to circumvent and delay this problem are
      suggested.

PMID- 14967452
TI  - The contribution of epidermal growth factor receptor (EGFR) signaling pathway to
      radioresistance in human gliomas: a review of preclinical and correlative
      clinical data.
AB  - PURPOSE: The epidermal growth factor receptor (EGFR) pathway is frequently
      upregulated in high-grade gliomas via gene amplification and by specific
      mutations that render EGFR constitutively active (EGFRvIII). METHODS AND
      MATERIALS: This review highlights EGFR's role in mediating radiation resistance
      in gliomas: underlying molecular mechanisms, with discussion of relevant
      preclinical and clinical correlative data. RESULTS: Preclinical and emerging
      clinical data suggest that EGFR signaling plays a potentially important role in
      mediating radiation resistance in human gliomas. CONCLUSIONS: Targeting EGFR
      alone, or in combination with its downstream mediators, represents a promising
      new approach for the management of glioma patients.

PMID- 14967453
TI  - The HER receptor family: a rich target for therapeutic development.
AB  - PURPOSE: The key role of the HER family of receptors in cancer has been widely
      acknowledged. HER receptor activation occurs via ligand binding or nonligand
      dependent receptor dimerization, initiating signals that promote tumorigenesis
      via cell proliferation, survival, migration, adhesion, and differentiation.
      Therapeutic strategies designed to target and inhibit HER activation that are in
      clinical development are reviewed, including examples of both small-molecule
      tyrosine kinase inhibitors and monoclonal antibodies. MATERIALS AND METHODS: A
      literature review. RESULTS: Tarceva is a potent, highly selective, reversible
      inhibitor of HER1/epidermal growth factor receptor tyrosine kinase with
      inhibitory activity against various in vitro and in vivo models of solid human
      tumors. Phase II trials in refractory non-small-cell lung, head-and-neck, and
      ovarian cancer have demonstrated clinical activity, including objective responses
      and prolonged, stable disease. Four Phase III trials are ongoing evaluating
      primarily the effect on survival of Tarceva in combination with chemotherapy. 2C4
      is a humanized anti-HER2 monoclonal antibody that binds to a broad, extracellular
      epitope, resulting in steric inhibition of HER-receptor complex formation that
      involves HER2. 2C4 has shown significant activity in xenograft models of
      prostate, lung, and breast cancer. 2C4's activity, unlike Herceptin's, is not
      dependent on HER2 amplification. This antibody is in early clinical development.
      CONCLUSION: The strategy of targeting the HER system has been further validated
      by early experience with Tarceva and 2C4. The optimal clinical benefit of these
      agents will likely involve combinations of biologic agents, with or without
      traditional chemotherapy, and will be guided by critical predictive diagnostic
      information.

PMID- 14967454
TI  - Rationale and clinical basis for combining gefitinib (IRESSA, ZD1839) with
      radiation therapy for solid tumors.
AB  - PURPOSE: The role of dysregulated epidermal growth factor receptor-tyrosine
      kinase (EGFR-TK) activity in promoting tumor resistance to radiation therapy is
      discussed, and evidence supporting the rationale for the use of gefitinib
      (IRESSA, ZD1839) to enhance tumor radiosensitivity is reviewed. METHODS AND
      MATERIALS: A review of the literature regarding the role of EGFR-TK signaling in
      tumor response to radiation therapy was conducted, and results were summarized
      from preclinical and clinical studies of gefitinib in the treatment of solid
      tumors alone and in combination with radiation therapy. RESULTS: Preclinical
      results indicate that EGFR-TK activity in tumors can block the cytotoxic effects
      of radiation therapy and enhance tumor repopulation, resulting in failure of
      local tumor control. In xenograft tumor models, gefitinib in combination with
      ionizing radiation resulted in additive to synergistic growth inhibition. In
      randomized clinical trials, gefitinib has demonstrated efficacy with favorable
      tolerability as monotherapy for patients with advanced non-small-cell lung cancer
      or head-and-neck carcinomas who had previously received standard therapies.
      CONCLUSIONS: These results indicate that there is potential for improved
      responses by combining gefitinib with radiation therapy in non-small-cell lung
      cancer, head-and-neck cancers, and other solid tumors.

PMID- 14967455
TI  - Adenoviral vector-mediated augmentation of epidermal growth factor receptor
      (EGFr) enhances the radiosensitization properties of anti-EGFr treatment in
      prostate cancer cells.
AB  - PURPOSE: To determine whether an adenoviral vector approach to the augmentation
      of epidermal growth factor receptor (EGFr) expression results in increased
      antiproliferative and radiosensitization properties of anti-EGFr antibody therapy
      in prostate cancer cells. METHODS AND MATERIALS: DU145 and LNCaP human prostate
      cancer cells were used to test the above question in vitro. An adenoviral vector
      was utilized to transduce cells with an EGFr transgene (AdEGFr). Immunoblots were
      performed to measure EGFr expression and EGFr tyrosine phosphorylation.
      Radiolabeled ligand studies were employed to test binding of epidermal growth
      factor to EGFr. Scatchard analyses allowed for quantification of the number of
      EGFrs. Standard immunohistochemistry was performed to assess EGFr expression.
      Cellular proliferation was assessed after various combinations of treatment.
      RESULTS: Studies of prostate carcinoma cells infected with AdEGFr demonstrated an
      increase in EGFr expression. This increase in expression correlated with
      increased function of EGFr. Specifically, increased EGFr expression also resulted
      in increased ligand binding, ligand-induced internalization of EGFr, and ligand
      induced EGFr tyrosine kinase activity that could be blocked with pre-exposure to
      IMC-C225 (an anti-EGFr monoclonal antibody). Transduction of the LNCaP cells with
      AdEGFr did not increase the antiproliferative effects of IMC-C225, but did
      significantly increase IMC-C225-induced radiosensitization as determined by cell
      proliferation. CONCLUSIONS: Augmentation of EGFr expression, through an
      adenoviral vector approach in prostate carcinoma cells, resulted in cells that
      demonstrated greater IMC-C225-induced radiosensitization compared to cells that
      were not treated with AdEGFr.

PMID- 14967456
TI  - Epidermal growth factor receptor and response of head-and-neck carcinoma to
      therapy.
AB  - PURPOSE: To present an overview of the significance of erbB tyrosine kinase
      family members as prognostic-predictive factors and as targets of therapeutic
      intervention in patients with head-and-neck carcinomas (HNCs). METHODS AND
      MATERIALS: The data of clinical studies addressing the correlation between the
      expression of erbB family tyrosine kinases, particularly epidermal growth factor
      receptor (EGFR), and the prognosis and pattern of failure were reviewed, along
      with the response of HNCs to EGFR antagonists such as a chimeric monoclonal
      antibody and a couple of small molecule tyrosine kinase inhibitors. RESULTS:
      Correlative biomarker studies showed that most HNCs express high levels of EGFR
      and/or other members of the erbB family. Several studies have demonstrated that
      patients with EGFR-overexpressing tumors had significantly worse overall
      survival. Compelling evidence has emerged showing that EGFR-overexpressing HNCs
      respond more poorly to radiotherapy (RT), although data of its impact on the
      response to chemotherapy are scarce. Clinical studies have so far showed that
      tyrosine kinase inhibitors have rather limited antitumor activities when given
      alone. Stimulated by promising preclinical data, the value of EGFR antagonists in
      the combined modality setting, particularly with RT, is being addressed in
      clinical trials. CONCLUSION: Members of the erbB receptor tyrosine kinase family,
      particularly EGFR, were found to be a strong biomarker for poor prognosis and HNC
      resistance to RT. The available data showed that EGFR antagonists given as single
      modality therapies yield rather limited antitumor activity. The results of trials
      testing the efficacy of combining EGFR antagonist with RT or chemotherapy will
      emerge within the next few years.

PMID- 14967457
TI  - Epidermal growth factor receptor and tumor response to radiation: in vivo
      preclinical studies.
AB  - PURPOSE: Evidence is rapidly mounting that dysregulated epidermal growth factor
      receptor (EGFR) signaling is one of the underlying mechanisms of more aggressive
      tumor behavior and increased tumor resistance to cytotoxic agents, including
      radiotherapy (RT). This has led to extensive preclinical and clinical studies
      aimed at developing effective treatment strategies that counteract EGFR-mediated
      signaling. In this article, we review preclinical studies, primarily from our
      laboratory, addressing the role of EGFR in tumor radioresponse and the use of
      C225, a human-mouse chimeric anti-EGFR monoclonal antibody, to improve the
      results of RT. METHODS AND MATERIALS: Mouse carcinomas were used to study the
      influence of EGFR on tumor radioresponse. EGFR expression was assessed by Western
      blot analysis, and cDNA transfection experiments were performed to determine a
      causal relationship between EGFR and tumor cell radioresistance. A431 human tumor
      xenografts growing in nude mice were used to test whether blockade of EGFR with
      C225 anti-EGFR antibody enhances tumor radioresponse. RESULTS: Our studies showed
      that high levels of EGFR were associated with decreased tumor radiocurability of
      murine carcinomas. The causal role of EGFR in mediating cellular resistance to RT
      was demonstrated by transfecting the EGFR cDNA into the cells with low levels of
      EGFR. The EGFR-high expression-transfected clones became more resistant to RT. RT
      activated EGFR and its downstream signaling pathways in radioresistant, but not
      in radiosensitive, tumors, which can be regarded as an adaptive response to
      radiation damage. Additional studies investigated whether blockade of EGFR and
      inhibition of EGFR-mediated downstream signaling can be exploited for therapeutic
      purposes. The results described here showed that treatment of human tumor
      xenografts with C225 can markedly enhance the tumor response to RT, as assessed
      by both tumor growth delay and the tumor cure rate. CONCLUSION: The findings from
      our in vivo preclinical studies suggest that overexpression of EGFR could serve
      as a predictor of tumor treatment outcome by RT and as a therapeutic target to
      enhance the efficacy of RT. This therapeutic strategy is currently being explored
      in patients with head-and-neck cancers.

PMID- 14967458
TI  - Radioimmunotherapy as a novel treatment regimen: 125I-labeled monoclonal antibody
      425 in the treatment of high-grade brain gliomas.
AB  - A Phase I/II clinical trial was undertaken between January 29, 1987 and January
      25, 1997 to assess the efficacy of (125)I-labeled monoclonal antibody 425 ((125)I
      MAb 425) in controlling high-grade brain gliomas. A total of 180 patients
      diagnosed with glioblastoma multiforme (GBM) and astrocytoma with anaplastic foci
      (AAF) were administered (125)I-MAb 425 as an adjuvant treatment. All underwent
      initial surgery followed by postoperative external beam radiation therapy and a
      cumulative dose of 140 mCi of (125)I-MAb 425. Biodistribution of radioactivity
      after antibody administration showed increased uptake in brain tumor cells due to
      enhanced expression of epidermal growth factor receptors. A longer half-life of
      (125)I-MAb 425 in brain tumor cells compared to blood was observed. All patients
      were followed up for at least 5 years. Overall actuarial survival range for GBM
      and AAF patients showed 4-150 and 4-270 months, respectively. GBM and AAF
      patients under age 40 years with a Karnofsky performance status >70 had an
      actuarial median survival of 22.5 and 65 months, respectively. This adjuvant
      therapy demonstrates a significant increase in median survival and should be
      considered in the management of high-grade brain gliomas.

PMID- 14967459
TI  - Combining EGFR inhibitors with radiation or chemotherapy: will preclinical
      studies predict clinical results?
AB  - PURPOSE: To highlight some of the preclinical data that examine the interaction
      of epidermal growth factor receptor (EGFR) inhibitors with radiotherapy and
      chemotherapy. METHODS AND MATERIALS: Recognition of the EGFR as an important
      regulator of tumor cell growth in the early 1980s stimulated the development of a
      series of molecules specifically designed to inhibit EGFR signaling as anticancer
      agents. Many of these agents have now matured and are in advanced clinical trial
      investigations, with tumor response rates on the order of 10-20% identified
      across a variety of human malignancies. Initially designed primarily as
      "cytostatic" agents, as opposed to "cytotoxic" agents, it is possible that the
      EGFR inhibitors will realize their optimal clinical impact when delivered in
      concert with conventional cytotoxic modalities such as radiotherapy and/or
      chemotherapy. RESULTS: Despite very strong in vitro and in vivo preclinical
      results, several major gaps remain in our knowledge regarding the EGFR inhibitor
      mechanisms of interaction with radiotherapy and chemotherapy, with considerable
      selection bias in the publication of preclinical data available to date.
      CONCLUSION: By acknowledging the limitations of the available preclinical data
      and by expanding our mechanistic understanding of EGFR inhibitor function in
      representative tumor model systems, we should enhance our capacity to predict the
      most rational and successful methods to combine EGFR inhibitors with cytotoxic
      modalities in future clinical trials.

PMID- 14967460
TI  - Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal
      growth factor receptor antibody.
AB  - The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, with
      an extracellular ligand-binding domain and intracellular tyrosine kinase domain.
      Ligand binding induces EGFR dimerization and autophosphorylation on several
      tyrosine residues in the intracellular domain, leading to mitogenic signal
      transduction. EGFR overexpression correlates with a poor prognosis and is often
      associated with malignant transformation in a variety of epithelial cancers. ABX
      EGF is a high-affinity (dissociation constant K(D) = 5 x 10(-11) M) fully human
      IgG2 monoclonal antibody against human EGFR. ABX-EGF binds EGFR and blocks
      receptor binding of EGF and transforming growth factor-alpha, inhibiting EGFR
      tyrosine phosphorylation and tumor cell activation. ABX-EGF prevents tumor
      formation and eradicates large, established A431 tumors in xenograft models.
      Tumor growth inhibition occurs at relatively low doses, without concomitant
      chemotherapy or radiotherapy. When combined with chemotherapeutic agents, ABX-EGF
      has resulted in additive antitumor activity. A Phase I clinical trial has
      demonstrated activity in several tumor types, and the results from a Phase II
      trial for renal cell cancer also showed modest activity. Therapy was generally
      well tolerated without statistically significant adverse events. Monoclonal
      antibody blockade of EGFR represents a new and exciting direction in cancer
      therapy.

PMID- 14967461
TI  - Emerging role of epidermal growth factor receptor inhibition in therapy for
      advanced malignancy: focus on NSCLC.
AB  - Combination chemotherapy regimens have emerged as the standard approach in
      advanced non-small-cell lung cancer. Meta-analyses have demonstrated a 2-month
      increase in median survival after platinum-based therapy vs. best supportive
      care, and an absolute 10% improvement in the 1-year survival rate. Just as
      importantly, cytotoxic therapy has produced benefits in symptom control and
      quality of life. Newer agents, including the taxanes, vinorelbine, gemcitabine,
      and irinotecan, have expanded our therapeutic options in the treatment of
      advanced non-small-cell lung cancer. Despite their contributions, we have reached
      a therapeutic plateau, with response rates seldom exceeding 30-40% in cooperative
      group studies and 1-year survival rates stable between 30% and 40%. It is
      doubtful that substituting one agent for another in various combinations will
      lead to any further improvement in these rates. The thrust of current research
      has focused on targeted therapy, and epidermal growth factor receptor inhibition
      is one of the most promising clinical strategies. Epidermal growth factor
      receptor inhibitors currently under investigation include the small molecules
      gefitinib (Iressa, ZD1839) and erlotinib (Tarceva, OSI-774), as well as
      monoclonal antibodies such as cetuximab (IMC-225, Erbitux). Agents that have only
      begun to undergo clinical evaluation include CI-1033, an irreversible pan-erbB
      tyrosine kinase inhibitor, and PKI166 and GW572016, both examples of dual kinase
      inhibitors (inhibiting epidermal growth factor receptor and Her2). Preclinical
      models have demonstrated synergy for all these agents in combination with either
      chemotherapy or radiotherapy, leading to great enthusiasm regarding their
      ultimate contribution to lung cancer therapy. However, serious clinical
      challenges persist. These include the identification of the optimal dose(s); the
      proper integration of these agents into popular, established cytotoxic regimens;
      and the selection of the optimal setting(s) in which to test these compounds.
      Both gefitinib and erlotinib have shown clinical activity in pretreated, advanced
      non-small-cell lung cancer, but placebo-controlled randomized Phase III studies
      evaluating gefitinib in combination with standard cytotoxic therapy, to our
      chagrin, have failed to demonstrate a survival advantage compared with
      chemotherapy alone.

PMID- 14967462
TI  - Epidermal growth factor receptor inhibitors in clinical development.
AB  - In cancer cells, aberrant signaling through the epidermal growth factor receptor
      (EGFR) activates pathways that stimulate many of the properties associated with
      neoplasia, including proliferation, migration, stromal invasion, tumor
      angiogenesis, and resistance to cell death-inducing signals. Because of the
      frequency of abnormalities in receptor signaling in human cancers, the EGFR is an
      attractive target for therapeutic development. Monoclonal antibodies and small
      molecule tyrosine kinase inhibitors are the two classes of agents that are the
      furthest advanced in clinical development. Although pharmacologic and mechanistic
      differences exist between the two classes, the results of preclinical studies
      suggest that both inhibit proliferation, have little normal tissue toxicity, and
      are additive/synergistic with standard therapies. The results from early clinical
      trials have indicated that both classes of agents are well tolerated and have
      antitumor activity. However, the first Phase III studies to be completed have not
      shown an improvement in survival with the addition of the monoclonal antibody
      C225 to cisplatin in patients with head-and-neck carcinoma or the addition of the
      kinase inhibitor ZD1839 to chemotherapy in patients with advanced lung cancer.
      Ongoing and future studies must address issues related to the selection of
      patients for study, dose and schedule of administration, monotherapy vs.
      combination treatment, and combinations with standard and investigational agents.

PMID- 14967463
TI  - Long-term changes in pulmonary function tests after definitive irradiation for
      lung cancer.

PMID- 14967465
TI  - In response to Li et al.: Concurrent chemoradiotherapy treatment of locally
      advanced pancreatic cancer: gemcitabine versus 5-fluorouracil, a randomized
      controlled study. IJROBP 2003;57:98-104.

PMID- 14967469
TI  - The modulation of thermal properties of vinblastine by cholesterol in membrane
      bilayers.
AB  - It has been shown that the partitioning of vinblastine in 1,2-dipalmitoyl-sn
      glycero-3-phosphatidylcholine (DPPC) single and multiple bilayer dispersions
      induces partial interdigitation of the lipid alkyl chains. Similar behavior has
      been observed for abietic and ursodeoxycholic acids and may well be generalized
      for the partitioning of bulky amphoteric molecules, which tend to localize in the
      vicinity of the polar heads. For the present study, differential scanning
      calorimetry (DSC) has been employed to investigate the role of lipid molecular
      characteristics such as the alkyl chain length and the polarity of the head
      group, as well as the impact of cholesterol upon vinblastine-induced
      interdigitation. It is found that vinblastine does not induce interdigitation in
      lipids with either shorter or longer alkyl chains than DPPC, or having head
      groups of different polarity. In addition, it is shown that the presence of
      cholesterol in the lipid bilayer tends to modulate the phase behavior of the
      lipid/vinblastine bilayer system. Preliminary studies show that such properties
      directly affect the encapsulation efficiency and the pharmacokinetics of
      liposomes.

PMID- 14967470
TI  - Exploring detergent insolubility in bovine hippocampal membranes: a critical
      assessment of the requirement for cholesterol.
AB  - The phenomenon of detergent insolubility of bovine hippocampal membranes in
      Triton X-100 was monitored by estimating the presence of phospholipids in the
      insoluble pellet. This represents a convenient and unambiguous assay and reports
      the dependence of the extent of phospholipid solubilization on detergent
      concentration. The advantage of this approach is its ability to accurately
      determine the extent of detergent insolubility in natural membranes. Importantly,
      our results show that when suboptimal concentrations of Triton X-100 are used for
      solubilization, interpretations of the mechanism and extent of detergent
      insolubility should be made with adequate caution. At concentrations of Triton X
      100 that leads to no further solubilization, approximately 44% of phospholipids
      are left insoluble at 4 degrees C in bovine hippocampal membranes. Cholesterol
      depletion using methyl-beta-cyclodextrin enhanced phospholipid solubilization at
      low detergent concentrations but produced no significant change in the amount of
      insoluble phospholipids at saturating detergent concentration. Progressive
      solubilization by the detergent resulted in insoluble membranes that contained
      lipids with higher fatty acyl chain order as reported by fluorescence
      polarization studies using 1,6-diphenyl-1,3,5-hexatriene (DPH). These results
      suggest that it is the presence of such lipids rather than their association with
      cholesterol that determines detergent insolubility in membranes.

PMID- 14967471
TI  - Diffusion and dynamics of penetratin in different membrane mimicking media.
AB  - The interaction between the cell-penetrating peptide (CPP) penetratin and
      different membrane mimetic environments has been investigated by two different
      NMR methods: 15N spin relaxation and translational diffusion. Diffusion
      coefficients were measured for penetratin in neutral and in negatively charged
      bicelles of different size, in sodium dodecyl sulfate micelles (SDS), and in
      aqueous solution. The diffusion coefficients were used to estimate the amount of
      free and bicelle/micelle-bound penetratin and the results revealed that
      penetratin binds almost fully to all studied membrane mimetics. 15N relaxation
      data for three sites in penetratin were interpreted with the model-free approach
      to obtain overall and local dynamics. Overall correlation times for penetratin
      were in agreement with findings for other peptides of similar size in the same
      solvents. Large differences in order parameters were observed for penetratin in
      the different membrane mimetics. Negatively charged surfaces were seen to
      restrict motional flexibility, while a more neutral membrane mimetic did not.
      This indicates that although the peptide binds to both bicelles and SDS micelles,
      the interaction between penetratin and the various membrane mimetics is
      different.

PMID- 14967472
TI  - Molecular dynamics study of the KcsA channel at 2.0-A resolution: stability and
      concerted motions within the pore.
AB  - The stability of the KcsA channel accommodating more than one ion in the pore has
      been studied with molecular dynamics. We have used the very last X-ray structure
      of the KcsA channel at 2.0-A resolution determined by Zhou et al. [Nature 414
      (2001) 43]. In this channel, six of the seven experimentally evidenced sites have
      been considered. We show that the protein remains very stable in the presence of
      four K+ ions (three in the selectivity filter and one in the cavity). The
      locations and the respective distances of the different K+ ions and water
      molecules (W), calculated within our KWKWKK sequence, also fits well with the
      experimental observations. The analysis of the K+ ions and water molecules
      displacements shows concerted file motions on the simulated time scale
      (approximately 1 ns), which could act as precursor to the diffusion of K+ ions
      inside the channel. A simple one-dimensional dynamical model is used to interpret
      the concerted motions of the ions and water molecules in the pore leading
      ultimately to ion transfer.

PMID- 14967473
TI  - Polarized distribution of Na+, K(+)-ATPase alpha-subunit isoforms in electrocyte
      membranes.
AB  - We have previously demonstrated that Na+, K(+)-ATPase activity is present in both
      differentiated plasma membranes from Electrophorus electricus (L.) electrocyte.
      Considering that the alpha subunit is responsible for the catalytic properties of
      the enzyme, the aim of this work was to study the presence and localization of
      alpha isoforms (alpha1 and alpha2) in the electrocyte. Dose-response curves
      showed that non-innervated membranes present a Na+, K(+)-ATPase activity 2.6-fold
      more sensitive to ouabain (I50=1.0+/-0.1 microM) than the activity of innervated
      membranes (I50=2.6+/-0.2 microM). As depicted in [3H]ouabain binding experiments,
      when the [3H]ouabain-enzyme complex was incubated in a medium containing
      unlabeled ouabain, reversal of binding occurred differently: the bound inhibitor
      dissociated 32% from Na+, K(+)-ATPase in non-innervated membrane fractions within
      1 h, while about 50% of the ouabain bound to the enzyme in innervated membrane
      fractions was released in the same time. These data are consistent with the
      distribution of alpha1 and alpha2 isoforms, restricted to the innervated and non
      innervated membrane faces, respectively, as demonstrated by Western blotting from
      membrane fractions and immunohistochemical analysis of the main electric organ.
      The results provide direct evidence for a distinct distribution of Na+, K(+)
      ATPase alpha-subunit isoforms in the differentiated membrane faces of the
      electrocyte, a characteristic not yet described for any polarized cell.

PMID- 14967474
TI  - pH gradient loading of anthracyclines into cholesterol-free liposomes: enhancing
      drug loading rates through use of ethanol.
AB  - Application of cholesterol-free liposomes as carriers for anticancer drugs is
      hampered, in part, because of standard pH gradient based loading methods that
      rely on incubation temperatures above the phase transition temperature (Tc) of
      the bulk phospholipid to promote drug loading. In the absence of cholesterol,
      liposome permeability is enhanced at these temperatures which, in turn, can
      result in the collapse of the pH gradient and/or unstable loading. Doxorubicin
      loading studies, for example, indicate that the drug could not be loaded
      efficiently into cholesterol-free DSPC liposomes. We demonstrated that this
      problem could be circumvented by the addition of ethanol as a permeability
      enhancer. Doxorubicin loading rates in cholesterol-free DSPC liposomes were 6.6
      fold higher in the presence of ethanol. In addition, greater than 90% of the
      added doxorubicin was encapsulated within 2 h at 37 degrees C, an efficiency that
      was 2.3-fold greater than that observed in the absence of ethanol. Optimal
      ethanol concentrations ranged from 10% to 15% (v/v) and these concentrations did
      not significantly affect liposome size, retention of an aqueous trap marker
      (lactose) or, most importantly, the stability of the imposed pH gradient. Cryo
      transmission electron micrographs of liposomes exposed to increasing
      concentrations of ethanol indicated that at 30% (v/v) perturbations to the lipid
      bilayer were present as evidenced by the appearance of open liposomes and bilayer
      sheets. Ethanol-induced increased drug loading was temperature-, lipid
      composition- and lipid concentration-dependent. Collectively, these results
      suggest that ethanol addition to preformed liposomes is an effective method to
      achieve efficient pH gradient-dependent loading of cholesterol-free liposomes at
      temperatures below the Tc of the bulk phospholipid.

PMID- 14967475
TI  - Dissociation constants of phenothiazine drugs incorporated in phosphatidylcholine
      bilayer of small unilamellar vesicles as determined by carbon-13 nuclear magnetic
      resonance spectrometric titration.
AB  - The dissociation constants (pKms) of the phenothiazine drugs promazine,
      chlorpromazine, and triflupromazine, incorporated in the phosphatidylcholine (PC)
      bilayer of small unilamellar vesicles (SUV), were investigated by a 13C nuclear
      magnetic resonance (NMR) titration method employing their N-13CH3 (ionizable
      group) labelled derivatives. Use of the labelled drugs enabled direct
      observations of the ionization equilibrium of the N-dimethyl group. A second
      derivative spectrophotometric study proved that 95-98% of the phenothiazine
      species in the sample solutions (200 microM phenothiazine in the presence of 27
      mM PC SUV) were incorporated into the PC bilayer, which simplified the
      calculation of pKm values by allowing that the phenothiazines in the aqueous
      phase could be neglected. The pKm values were calculated from the chemical shift
      dependence of the N-dimethyl 13C NMR signal on the pH value of sample solutions.
      The pKm values obtained were smaller than those measured in aqueous solutions by
      about one unit. The existence of cholesterol (30 mol%) in the PC bilayer showed
      little effect on the pKm values, suggesting that cholesterol in the bilayer does
      not largely affect the interfacial region where the N-dimethyl group of the
      incorporated phenothiazines is located. The results offered clear evidence for
      the pKm decrease and provided their precise values.

PMID- 14967476
TI  - Does VDAC insert into membranes in random orientation?
AB  - It is widely accepted that voltage-dependent anion-selective channel (VDAC)
      inserts into planar lipid bilayers in a random orientation. This is in contrast
      to the well-documented oriented insertion of various channel-forming proteins.
      Because of the potential importance of this issue, we have examined the
      orientation of VDAC inserted in membranes. The time constants of the VDAC-current
      relaxation in response to applied positive and negative voltage pulses were used
      to characterize the channel orientation. We have found that VDAC channels can be
      separated into two groups according to differences in the time constant ratio.
      The difference in time constant ratio between the two main groups of VDAC
      channels was quantitative, and not qualitative as would be expected for opposite
      topologies. This finding allows us to hypothesize that both groups of VDAC
      channels possess a qualitatively similar asymmetry with respect to the
      localization of voltage-gated domains and, consequently, with respect to its
      entire molecular structure. The probability of having each type of VDAC channel
      conformation is predetermined by the protein structure in aqueous solution. A
      striking resemblance between asymmetry in voltage sensitivity at the single
      channel and multi-channel levels was also demonstrated. The first inserted
      channel seems to direct subsequent insertions of channels with a similar
      conformation.

PMID- 14967477
TI  - Reconstitution into liposomes and functional characterization of the carnitine
      transporter from renal cell plasma membrane.
AB  - The carnitine transporter was solubilized from rat renal apical plasma membrane
      (brush-border membrane) with C12E8 and reconstituted into liposomes by removing
      the detergent from mixed micelles by hydrophobic chromatography on Amberlite XAD
      4. The reconstitution was optimised with respect to the protein concentration,
      the detergent/phospholipid ratio and the number of passages through a single
      Amberlite column. The reconstituted carnitine transporter catalysed a first-order
      antiport reaction (carnitine/carnitine or carnitine/substrate) stimulated by
      external, not internal, Na+, with a positive cooperativity. Na+ was co
      transported with carnitine. Optimal activity was found between pH 5.5 and pH 6.0.
      The sulfhydryl reagents MTSES, MTSET and mercurials strongly inhibited the
      transport. Substrate analogues inhibited the transport; the most effective were
      acylcarnitines and betaine, followed by dimethylglicine, tetraethylammonium and
      arginine. Besides carnitine, only acylcarnitines and betaine were efficiently
      translocated. The Km for carnitine on the external and internal side of the
      transporter was 0.08 and 1.2 mM, respectively. The transporter is asymmetrical
      and it is unidirectionally inserted into the proteoliposomal membrane with an
      orientation corresponding to that of the native membrane. The reconstituted
      carnitine transporter corresponds, very probably, to the OCTN2 protein.

PMID- 14967478
TI  - Dynamics of pH-dependent self-association and membrane binding of a dicarboxylic
      porphyrin: a study with small unilamellar vesicles.
AB  - Steady-state and stopped-flow measurements of the absorbance and fluorescence of
      aqueous solutions were performed to characterize the pH-dependent ionization and
      aggregation states of deuteroporphyrin. Porphyrin self-association promoted by
      neutralization of the carboxylic groups takes place within a few milliseconds
      impeding characterization of the monomer ionization states. Extrapolation at
      infinite dilution of the values obtained from steady-state measurements yielded
      the pKs of the carboxylic groups (6.6, 5.3) and inner nitrogens (4.1, 2.3). The
      kinetics of interactions of the porphyrin with unilamellar fluid state
      dioleoylphosphatidylcholine vesicles was examined in a large pH range, with focus
      on the entry step. From alkaline pH to a value of 6.5, the entrance rate is
      maximal (1.69 x 10(6) M(-1) s(-1) versus phospholipid concentration). It
      decreases to 2.07 x 10(5) M(-1) s(-1) at lower pH with an apparent pK of 5.39.
      This effect appears to be related to the formation of porphyrin dimer rather than
      to the protonation of inner nitrogen. In keeping with previous data, these
      results support the concept of a pH-mediated selectivity of carboxylic porphyrins
      for tumor. They also indicate that the propensity of these molecules to self
      associate at low pH could yield to some retention in acidic intracellular
      vesicles of the endosome/lysosome compartment.

PMID- 14967479
TI  - Identification of membrane-active regions of the HIV-1 envelope glycoprotein gp41
      using a 15-mer gp41-peptide scan.
AB  - The identification of membrane-active regions of the ectodomain of the HIV-1
      envelope glycoprotein gp41 has been made by determining the effect on membrane
      integrity of a 15-mer gp41-derived peptide library. By monitoring the effect of
      this peptide library on membrane leakage, we have identified three regions on the
      gp41 ectodomain with membrane-interacting capabilities: Region 1, which would
      roughly correspond to the polar sequence which follows the fusion domain and
      extends to the N-terminal heptad repeat region; Region 2, which would correspond
      to the immunodominant loop; and Region 3, which would correspond to the pre
      transmembrane region of gp41. The identification of these three regions supports
      their direct role in membrane fusion as well as facilitating the future
      development of HIV-1 entry inhibitors.

PMID- 14967480
TI  - Indoleamine 2,3-dioxygenase activity and L-tryptophan transport in human breast
      cancer cells.
AB  - The activity and expression of indoleamine 2,3-dioxygenase together with L
      tryptophan transport has been examined in cultured human breast cancer cells. MDA
      MB-231 but not MCF-7 cells expressed mRNA for indoleamine 2,3-dioxygenase.
      Kynurenine production by MDA-MB-231 cells, which was taken as a measure of enzyme
      activity, was markedly stimulated by interferon-gamma (1000 units/ml).
      Accordingly, L-tryptophan utilization by MDA-MB-231 cells was enhanced by
      interferon-gamma. 1-Methyl-DL-tryptophan (1 mM) inhibited interferon-gamma
      induced kynurenine production by MBA-MB-231 cells. Kynurenine production by MCF-7
      cells remained at basal levels when cultured in the presence of interferon-gamma.
      L-Tryptophan transport into MDA-MB-231 cells was via a Na(+)-independent, BCH
      sensitive pathway. It appears that system L (LAT1/CD98) may be the only pathway
      for l-tryptophan transport into these cells. 1-Methyl-D,L-tryptophan trans
      stimulated l-tryptophan efflux from MDA-MB-231 cells and thus appears to be a
      transported substrate of system L. The results suggest that system L plays an
      important role in providing indoleamine-2,3-dioxygenase with its main substrate,
      L-tryptophan, and suggest a mechanism by which estrogen receptor-negative breast
      cancer cells may evade the attention of the immune system.

PMID- 14967483
TI  - Post-transcription cleavage generates the 3' end of F17R transcripts in vaccinia
      virus.
AB  - Most vaccinia virus intermediate and late mRNAs possess 3' ends that are
      extremely heterogeneous in sequence. However, late mRNAs encoding the cowpox A
      type inclusion protein (ATI), the second largest subunit of the RNA polymerase,
      and the late telomeric transcripts possess homogeneous 3' ends. In the case of
      the ATI mRNA, it has been shown that the homogeneous 3' end is generated by a
      post-transcriptional endoribonucleolytic cleavage event. We have determined that
      the F17R gene also produces homogeneous transcripts generated by a post
      transcriptional cleavage event. Mapping of in vivo mRNA shows that the major 3'
      end of the F17R transcript maps 1262 nt downstream of the F17R translational
      start site. In vitro transcripts spanning the in vivo 3' end are cleaved in an in
      vitro reaction using extracts from virus infected cells, and the site of cleavage
      is the same both in vivo and in vitro. Cleavage is not observed using extract
      from cells infected in the presence of hydroxyurea; therefore, the cleavage
      factor is either virus-coded or virus-induced during the post-replicative phase
      of virus replication. The cis-acting sequence responsible for cleavage is
      orientation specific and the factor responsible for cleavage activity has
      biochemical properties similar to the factor required for cleavage of ATI
      transcripts. Partially purified cleavage factor generates cleavage products of
      expected size when either the ATI or F17R substrates are used in vitro, strongly
      suggesting that cleavage of both transcripts is mediated by the same factor.

PMID- 14967484
TI  - Phylogenetic analysis and reclassification of caprine and ovine lentiviruses
      based on 104 new isolates: evidence for regular sheep-to-goat transmission and
      worldwide propagation through livestock trade.
AB  - We performed a phylogenetic analysis of caprine and ovine lentiviruses using long
      sequences in gag and pol of 104 new Swiss isolates and six available
      corresponding database sequences. Forty-five isolates, forming five sequence
      clusters, were unclassifiable by the present classification. Pairwise DNA
      distance analysis indicated different categories of relatedness, requiring a new
      classification system. We propose four principal sequence groups, A-D, which
      differ by 25-37%. Groups A and B are further divided into subtypes which differ
      by 15-27%. Group D and four of the seven group A subtypes, A3, A4, A5 and A7, are
      formed by new Swiss isolates. Molecular epidemiology revealed that Swiss B1
      strains differed no more from French, Brazilian or US strains than from each
      other, suggesting virus propagation through international livestock trade.
      Furthermore, infection of goats by subtypes A3 or A4 was significantly associated
      with documented contact with sheep, which also harbor these subtypes, thus
      indicating regularly occurring sheep-to-goat transmission.

PMID- 14967485
TI  - Epitopes recognized by CBV4 responding T cells: effect of type 1 diabetes and
      associated HLA-DR-DQ haplotypes.
AB  - The present study aimed at characterizing the epitopes recognized by
      coxsackievirus B4 (CBV4)-specific T-cell lines established from 23 children with
      type 1 diabetes (T1D) and 29 healthy children with T1D risk-associated HLA
      genotypes. Responsiveness to VP1 region was dependent on the specific infection
      history as 55% of the T-cell lines from donors with neutralizing antibodies to
      CBV serotypes responded to VP1 peptides compared to none of the T-cell lines from
      other donors (P = 0.01). The pattern of recognized peptides was dependent of the
      HLA genotype. Forty-two percent of the T-cell lines from donors carrying the HLA
      (DR4)-DQB1*0302 haplotype responded to VP1 peptides 71-80 compared to none of the
      T-cell lines from donors without this haplotype (P = 0.02). No evidence for the
      existence of diabetes-specific epitopes was found. Only few epitopes were
      exclusive recognized by T cells from diabetic children, and in each case only one
      or two T-cell lines were responding.

PMID- 14967486
TI  - HCV E2 glycoprotein: mutagenesis of N-linked glycosylation sites and its effects
      on E2 expression and processing.
AB  - An expression system for analysis of the synthesis and processing of the E2
      glycoprotein of a hepatitis C virus (HCV) genotype 1a strain was developed in
      transiently transfected cells. E2 proteins representing the entire length of the
      protein, including the transmembrane segment (E2) as well as two truncated
      versions (E2(660) and E2(715)), were characterized for acquisition of N-linked
      glycans and transport to the media of transfected cells. To investigate the
      utilization of the 10 potential N-linked glycosylation sites on this E2 protein,
      a series of mutations consisting of single or multiple (two, three, four or
      eight) ablations of asparagine residues in the background of the E2(660)
      construct were analyzed. E2(660) proteins harboring single or multiple site
      mutations were produced at levels similar to that of wild-type protein, but
      secretion of the single mutants was mildly diminished, and elimination of two or
      more sites dramatically reduced delivery of the protein to the media. Similar
      results were obtained in Huh-7 cells with respect to intracellular synthesis and
      secretion of the mutant proteins. Analysis of oligosaccharide composition using
      endoglycosidase digestion revealed that all of the glycan residues on the
      intracellular forms of E2(660), E2(715), and E2 contained N-linked glycans
      modified into high-mannose carbohydrates, in contrast to the secreted forms,
      which were endo H resistant. The parental E2(660) protein could be readily
      detected in Huh-7 cells using anti-polyhistidine or antibody to recombinant E2.
      In contrast, E2(660) lacking the eight N-linked glycans was expressed but not
      detectable with anti-E2 antibody, and proteins lacking four glycans exhibited
      reduced reactivity. These experiments provide direct evidence that the presence
      of multiple N-linked glycans is required for the proper folding of the E2 protein
      in the ER and secretory pathway as well as for formation of its antigenic
      structure.

PMID- 14967487
TI  - Identification and partial characterization of Taastrup virus: a newly identified
      member species of the Mononegavirales.
AB  - We present a 8904-nt sequence of the central part of the RNA genome of a novel
      virus with a filovirus-like, nonidentical morphology named Taastrup virus (TV)
      detected in the leafhopper Psammotettix alienus. Sequence analysis identified
      five potential open reading frames (ORFs) and a complex pattern of homologies to
      various members of the Mononegavirales suggests a genome organization with the
      following order of genes: 3'-N-P-M-G-L-5'. Sequence analyses reveal an unusually
      large glycoprotein (G) containing both potential O-linked (14) and N-linked (9)
      glycosylation sites-a feature shared with the glycoproteins of Filoviridae and
      Pneumovirinae, and a nucleoprotein (N) with homology to the nucleoprotein of
      viral hemorrhagic septicemia virus (VHSV), a member of the Rhabdoviridae. Highly
      conserved domains were identified in the RNA-dependent RNA polymerase (L) between
      TV and other viruses within the order of Mononegavirales, and homology was found
      in particular with members of the Rhabdoviridae. The sequence similarities and
      the unique filovirus-like but nonidentical morphology unambiguously refer this
      newly identified virus to the order of Mononegavirales but to no family more than
      any, to other within the order.

PMID- 14967488
TI  - The small delta antigen of hepatitis delta virus is an acetylated protein and
      acetylation of lysine 72 may influence its cellular localization and viral RNA
      synthesis.
AB  - Hepatitis delta virus (HDV) is a single-stranded RNA virus that encodes two viral
      nucleocapsid proteins named small and large form hepatitis delta antigen (S-HDAg
      and L-HDAg). The S-HDAg is essential for viral RNA replication while the L-HDAg
      is required for viral assembly. In this study, we demonstrated that HDAg are
      acetylated proteins. Metabolic labeling with [(3)H]acetate revealed that both
      forms of HDAg could be acetylated in vivo. The histone acetyltransferase (HAT)
      domain of cellular acetyltransferase p300 could acetylate the full-length and the
      N-terminal 88 amino acids of S-HDAg in vitro. By mass spectrometric analysis of
      the modified protein, Lys-72 of S-HDAg was identified as one of the acetylation
      sites. Substitution of Lys-72 to Arg caused the mutant S-HDAg to redistribute
      from the nucleus to the cytoplasm. The mutant reduced viral RNA accumulation and
      resulted in the earlier appearance of L-HDAg. These results demonstrated that
      HDAg is an acetylated protein and mutation of HDAg at Lys-72 modulates HDAg
      subcellular localization and may participate in viral RNA nucleocytoplasmic
      shuttling and replication.

PMID- 14967489
TI  - Vp130, a chloroviral surface protein that interacts with the host Chlorella cell
      wall.
AB  - A protein, Vp130, that interacts with the host cell wall was isolated from
      Chlorovirus CVK2. From its peptide sequence, the gene for Vp130 was identified on
      the PBCV-1 genomic sequence as an ORF combining A140R and A145R. In Vp130, the N
      terminus was somehow modified and the C-terminus was occupied by 23-26 tandem
      repeats of a PAPK motif. In the internal region, Vp130 contained seven repeats of
      70-73 amino acids, each copy of which was separated by PAPK sequences. This
      protein was well conserved among NC64A viruses. A recombinant rVp130N protein
      formed in Escherichia coli was shown not only to bind directly to the host cell
      wall in vitro but also to specifically bind to the host cells, as demonstrated by
      fluorescence microscopy. Because externally added rVp130N competed with CVK2 to
      bind to host cells, Vp130 is most likely to be a host-recognizing protein on the
      virion.

PMID- 14967490
TI  - Molecular pathways executing the "trophic sentinel" response in HPV-16 E7
      expressing normal human diploid fibroblasts upon growth factor deprivation.
AB  - In response to oncogenic insults, normal human cells execute a defense response
      that culminates in cellular suicide, apoptosis. Normal human diploid fibroblasts
      expressing the human papillomavirus type 16 (HPV-16) E7 oncoprotein are
      predisposed to apoptosis when they are deprived of growth factors. Even though a
      dominant negative p53 mutant abrogates the cell death response, it is not
      accompanied by p53 phosphorylation, the DNA binding capacity of p53 remains
      unaltered, and no activation of common p53-dependent transcriptional targets is
      observed. Expression of two insulin-like growth factor-1 binding proteins, IGFBP
      2 and -5, is increased presumably in response to enhanced NF-kappaB activity in
      HPV-16 E7-expressing serum-starved cells. Phosphorylation of AKT, an important
      modulator of IGF-1 survival signaling, is lower in serum-starved E7-expressing
      cells, and exogenously added IGF-1 can partially inhibit the cell death response.
      This suggests that IGFBP-2 and -5 may limit IGF-1 availability thus decreasing
      survival signaling. Caspase 3 but not caspase 8 is activated in serum-starved HPV
      16 E7-expressing cells. Caspase inhibition affects nuclear DNA fragmentation, but
      cell death is not inhibited. Although mitochondria play important roles in
      caspase-dependent as well as -independent forms of cell death, there is no
      evidence for cytochrome c release and thus for mitochondrial permeabilization in
      growth factor deprived HPV-16 E7-expressing cells.

PMID- 14967491
TI  - Avian reovirus nonstructural protein microNS forms viroplasm-like inclusions and
      recruits protein sigmaNS to these structures.
AB  - The M3 genome segment of avian reovirus 1733, which encodes the nonstructural
      protein microNS, is 1996 nucleotides long and contains a long open reading frame
      that is predicted to encode a polypeptide of 635 amino acid residues. Examination
      of the deduced amino acid sequence of microNS revealed the presence of two
      regions near its carboxyl terminus with a high probability of forming alpha
      helical coiled coils. Expression of the M3 gene in both infected and transfected
      cells revealed that this gene specifies two protein isoforms that are recognized
      by a microNS-specific antiserum. Only the larger microNS isoform, but not the
      smaller one, interacts with the nonstructural protein sigmaNS in infected cells,
      suggesting that the two isoforms play different roles during avian reovirus
      infection. In the second part of this study, we show that microNS and the
      nonstructural protein sigmaNS colocalize throughout the viral life cycle in large
      and small phase-dense globular cytoplasmic inclusions, which are believed to be
      the sites of viral replication and assembly. Individual expression of these
      proteins in transfected cells of avian and mammalian origin revealed that while
      microNS is able to form inclusions in the absence of other viral proteins,
      sigmaNS distributes diffusely throughout the cytoplasm in the absence of microNS.
      These data suggest that microNS is the minimal viral factor required for
      inclusion formation during avian reovirus infection. On the other hand, our
      findings that sigmaNS associates with microNS in infected cells, and that sigmaNS
      colocalizes with microNS in viroplasm-like inclusions when the two proteins are
      coexpressed in transfected cells, suggest that microNS mediates the association
      of sigmaNS to inclusions in avian reovirus-infected cells.

PMID- 14967492
TI  - The two envelope membrane glycoproteins of Tomato spotted wilt virus show
      differences in lectin-binding properties and sensitivities to glycosidases.
AB  - Tomato spotted wilt virus (TSWV, Genus: Tospovirus, Family: Bunyaviridae) is a
      major constraint to the production of several different crops of agronomic and
      horticultural importance worldwide. The amino acid sequence of the two envelope
      membrane glycoproteins, designated as G(N) (N-terminal) and G(C) (C-terminal), of
      TSWV contain several tripeptide sequences, Asn-Xaa-Ser/Thr, suggesting that the
      proteins are N-glycosylated. In this study, the lectin-binding properties of the
      viral glycoproteins and their sensitivities to glycosidases were examined to
      obtain information on the nature of potential oligosaccharide moieties present on
      G(N) and G(C). The viral proteins were separated by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis (SDS-PAGE) and probed by affinoblotting using
      a battery of biotinylated lectins with specificity to different oligosaccharide
      structures. G(C) showed strong binding with five mannose-binding lectins, four N
      acetyllactosamine-binding lectins and one fucose-binding lectin. G(N) was
      resolved into two molecular masses and only the slow migrating form showed
      binding, albeit to a lesser extent than G(C), with three of the five mannose
      binding lectins. The N-acetyllactosamine- and fucose-specific lectins did not
      bind to either molecular mass form of G(N). None of the galactose-, N
      acetylgalactosamine-, or sialic acid-binding lectins tested showed binding
      specificity to G(C) or G(N). Treatment of the denatured virions with
      endoglycosidase H and peptide:N-glycosidase F (PNGase F) resulted in a
      significant decrease in the binding of G(C) to high mannose- and N
      acetyllactosamine-specific lectins. However, no such differences in lectin
      binding were apparent with G(N). These results indicate the presence of N-linked
      oligosaccharides of high mannose- and complex-type on G(C) and possibly high
      mannose-type on G(N). Differences in the extent of binding of the two envelope
      glycoproteins to different lectins suggest that G(C) is likely to be more heavily
      N-glycosylated than G(N). No evidence was observed for the presence of O-linked
      oligosaccharides on G(N) or G(C).

PMID- 14967493
TI  - Optimization of a multi-gene HIV-1 recombinant subtype CRF02_AG DNA vaccine for
      expression of multiple immunogenic forms.
AB  - We developed an AIDS vaccine for Western and West-Central Africa based on a DNA
      plasmid vector expressing HIV-1 recombinant subtype CRF02_AG gag, pol, and env
      genes. To optimize the production of noninfectious HIV-like particles (VLPs) and
      potentially improve the effectiveness of the vaccine, we generated four potential
      vaccine constructs: the parental (IC2) and three modifications (IC25, IC48, and
      IC90) containing mutations within the HIV protease. While the parental construct
      IC2 expressed aggregates of Gag proteins, the IC25 construct resulted in the
      production of immature VLPs (the core comprises unprocessed Pr(55Gag)). The
      remaining two constructs (IC48 and IC90) produced mature VLPs (the core comprises
      processed capsid p24) in addition to immature VLPs and aggregates of Gag
      proteins. VLPs incorporated significant levels of mature gp120 envelope
      glycoprotein. Importantly, the mature VLPs were fusion competent and entered
      coreceptor-specific target cells. The production of multiple antigenic forms,
      including fusion-competent VLPs, by candidate DNA vaccine constructs may provide
      immunologic advantages for induction of protective cellular and humoral responses
      against HIV-1 proteins.

PMID- 14967494
TI  - Reptilian reovirus: a new fusogenic orthoreovirus species.
AB  - The fusogenic subgroup of orthoreoviruses contains most of the few known examples
      of non-enveloped viruses capable of inducing syncytium formation. The only
      unclassified orthoreoviruses at the species level represent several fusogenic
      reptilian isolates. To clarify the relationship of reptilian reoviruses (RRV) to
      the existing fusogenic and nonfusogenic orthoreovirus species, we undertook a
      characterization of a python reovirus isolate. Biochemical, biophysical, and
      biological analyses confirmed the designation of this reptilian reovirus (RRV)
      isolate as an unclassified fusogenic orthoreovirus. Sequence analysis revealed
      that the RRV S1 and S3 genome segments contain a novel conserved 5'-terminal
      sequence not found in other orthoreovirus species. In addition, the gene
      arrangement and the coding potential of the bicistronic RRV S1 genome segment
      differ from that of established orthoreovirus species, encoding a predicted
      homologue of the reovirus cell attachment protein and a unique 125 residue p14
      protein. The RRV S3 genome segment encodes a homologue of the reovirus sigma
      class major outer capsid protein, although it is highly diverged from that of
      other orthoreovirus species (amino acid identities of only 16-25%). Based on
      sequence analysis, biological properties, and phylogenetic analysis, we propose
      this python reovirus be designated as the prototype strain of a fifth species of
      orthoreoviruses, the reptilian reoviruses.

PMID- 14967495
TI  - Characterization of bacteriophage KVP40 and T4 RNA ligase 2.
AB  - Bacteriophage T4 RNA ligase 2 (Rnl2) exemplifies a subfamily of RNA strand
      joining enzymes that includes the trypanosome RNA editing ligases. A homolog of
      T4 Rnl2 is encoded in the 244-kbp DNA genome of vibriophage KVP40. We show that
      the 335-amino acid KVP40 Rnl2 is a monomeric protein that catalyzes RNA end
      joining through ligase-adenylate and RNA-adenylate (AppRNA) intermediates. In the
      absence of ATP, pre-adenylated KVP40 Rnl2 reacts with an 18-mer 5'-PO(4) single
      strand RNA (pRNA) to form an 18-mer RNA circle. In the presence of ATP, Rnl2
      generates predominantly AppRNA. Isolated AppRNA can be circularized by KVP40 Rnl2
      in the absence of ATP. The reactivity of phage Rnl2 and the distribution of the
      products are affected by the length of the pRNA substrate. Whereas 18-mer and 15
      mer pRNAs undergo intramolecular sealing by T4 Rnl2 to form monomer circles, a 12
      mer pRNA is ligated intermolecularly to form dimers, and a 9-mer pRNA is
      unreactive. In the presence of ATP, the 15-mer and 12-mer pRNAs are converted to
      AppRNAs, but the 9-mer pRNA is not. A single 5' deoxynucleotide substitution of
      an 18-mer pRNA substrate has no apparent effect on the 5' adenylation or
      circularization reactions of T4 Rnl2. In contrast, a single deoxyribonucleoside
      at the 3' terminus strongly and selectively suppresses the sealing step, thereby
      resulting in accumulation of high levels of AppRNA in the absence of ATP. The ATP
      dependent "capping" of RNA with AMP by Rnl2 is reminiscent of the capping of
      eukaryotic mRNA with GMP by GTP:RNA guanylyltransferase and suggests an
      evolutionary connection between bacteriophage Rnl2 and eukaryotic RNA capping
      enzymes.

PMID- 14967496
TI  - Kinetics of in vitro adsorption and entry of papillomavirus virions.
AB  - There has been much incongruence in reports addressing the rate at which
      papillomaviruses enter cultured cells. We used a recently developed QRT-PCR assay
      (J. Virol. Methods 111 (2003) 135) to analyze the expression, adsorption, and
      entry kinetics of human papillomavirus type 11 (HPV-11) in multiple cell lines.
      Parallel experiments with HPV-40 and cottontail rabbit papillomavirus (CRPV) were
      also performed with biologically relevant lines. Infection was determined by the
      expression of early transcripts containing the E1 E4 splice junction. Results
      support previous observations that papillomaviruses may enter cultured cells much
      more slowly than rates reported for similarly structured viruses (Virology 207
      (1995) 136; Virology 307 (2003) 1; J. Virol. 75 (2001) 1565). Additionally, our
      data suggest that, following adsorption to the cell surface, capsomeric structure
      remains largely unchanged for many hours as HPV-11 virions remain equally
      susceptible to neutralization by a nonspecific microbicide and by L1-specific
      monoclonal antibodies (MAb) targeting both linear and conformationally sensitive
      epitopes.

PMID- 14967497
TI  - Fuzzy rule-based models for decision support in ecosystem management.
AB  - To facilitate decision support in the ecosystem management, ecological expertise
      and site-specific data need to be integrated. Fuzzy logic can deal with highly
      variable, linguistic, vague and uncertain data or knowledge and, therefore, has
      the ability to allow for a logical, reliable and transparent information stream
      from data collection down to data usage in decision-making. Several environmental
      applications already implicate the use of fuzzy logic. Most of these applications
      have been set up by trial and error and are mainly limited to the domain of
      environmental assessment. In this article, applications of fuzzy logic for
      decision support in ecosystem management are reviewed and assessed, with an
      emphasis on rule-based models. In particular, the identification, optimisation,
      validation, the interpretability and uncertainty aspects of fuzzy rule-based
      models for decision support in ecosystem management are discussed.

PMID- 14967498
TI  - The potential of Lolium perenne for revegetation of contaminated soil from a
      metallurgical site.
AB  - A greenhouse study was carried out to determine the possibility of using Lolium
      perenne for revegetation of soil from a former ferrous metallurgical plant
      (Naples, South Italy) contaminated by Cu, Pb and Zn at levels above current
      Italian regulatory limits. Surface soil samples (0-40 cm) from the facility area
      where raw minerals were disposed (RM1 and RM2), from a nearby unpolluted
      cultivated soil (C) as control and a 1:3 mixture of the control with the polluted
      ones (RM1+C and RM2+C) were utilized for the experiment. Revegetation trials were
      conducted in the greenhouse. At 90 days from seeding, shoot length, chlorophyll
      content, biomass yield, plant metal uptake and changes of organic carbon content
      and metal distribution among soil extractable phases defined by sequential
      extraction were determined. In the mixed substrates (RM1+C and RM2+C)
      concentrations of Cu, Pb and Zn were still two to three times higher than the
      Italian regulatory limits. Plants were healthy with 100% survival in all
      substrates, with no macroscopic symptoms of metal toxicity. The high pH of the
      soil could be one of the most important parameters responsible for the limited
      plant availability of the metals. On RM1, RM2 and mixed media, plants experienced
      retarded growth, reduced shoot length and biomass yield and higher total
      chlorophyll content compared to those cropped on the control soil, without any
      evident phytotoxic symptoms. In RM1 and RM2, the plant contents of Cu (19.3 and
      12.6 mg kg(-1)), Pb (0.98 and 0.67 mg kg(-1)) and Zn (99 and 88 mg kg(-1)) were
      higher than that of plants grown on non-contaminated soil (Cu 10.1, Pb < 0.2, Zn
      79 mg kg(-1)), but still in the range of physiologically acceptable levels. The
      distribution of metals in soil was slightly affected by Lolium growth with
      changes only regarding the organic-bound Cu and Zn pool, with reduction up to
      24%. Results indicated that an acceptable healthy vegetative cover can be
      achieved on the contaminated soil by the proposed revegetation approach and that
      metals will remain stable over the study period with slight variation of the more
      available metal forms.

PMID- 14967499
TI  - Pearl aquaculture-profitable environmental remediation?
AB  - Bivalve molluscs are filter feeders, with pearl oysters able to filter water at
      rates up to 25 lh(-1)g(-1) of dry wt. tissue. Since this process leads to rapid
      bioaccumulation of recalcitrant pollutants such as heavy metals, organochlorine
      pesticides and hydrocarbons from impacted sites, it has prompted the widespread
      use of molluscs as biomonitors to quantify levels of marine pollution. This paper
      proposes pearl oyster deployment as a novel bioremediation technology for
      impacted sites to remove toxic contaminants, reduce nutrient loads and lower
      concentrations of microbial pathogens. Estimates extrapolated from the literature
      suggest that a modest pearl oyster farm of 100 t oyster material per year could
      remove 300 kg heavy metals plus 24 kg of organic contaminants via deposition into
      the tissue and shell. Furthermore, it was estimated that up to 19 kg of nitrogen
      may be removed from the coastal ecosystem per tonne of pearl oyster harvested.
      Pearl oysters are also likely to filter substantial amounts of sewage associated
      microbial pathogens from the water column. Method of cultivation and site
      selection are the key to minimising negative environmental impacts of bivalve
      cultivation. Deployment of oysters at sites with high nutrient and contaminant
      loadings would be advantageous, as these compounds would be removed from the
      ecosystem whilst generating a value-added product. Future potential may exist for
      harvesting bio-concentrated elements for commercial production.

PMID- 14967500
TI  - Element migration from glass compositions containing no added lead.
AB  - Six crystal glass compositions without added lead were used to prepare standard
      beakers having a volume of ca. 240 ml. The experimentally determined
      concentrations of the elements in the glass beakers were in satisfactory
      agreement with the theoretically predicted values. The degree of leaching of
      selected elements from these beakers was determined using 4% acetic acid as
      described in the ISO 7086-1:2000 standard test. In addition, to the degree of
      leaching by 4% acetic acid, migration into cola, red wine, 40% ethanol and 0.3%
      citric acid was also determined. Elements tested included antimony, barium,
      bismuth and zinc as these were considered to be of most interest. The results
      show that it is possible to produce durable glass containing no added lead. The
      overall quality of the glasses was good and the concentrations of the various
      elements migrating (leaching) into the various test solutions used was very small
      and it is clear that they would not present a hazard to consumers in the event
      that they were to use glasses of any of these compositions for consumption of
      either alcoholic or non-alcoholic beverages. The original ISO7086-1:2000 test
      using a 4% acetic acid leaching solution was developed to test for lead migration
      from crystal containing added lead and ceramic ware containing lead glazes or
      colouring. This work also shows that it is an excellent leaching agent for
      assessing the safety of crystal containing no added lead as it gave the highest
      degree of migration for all the glass compositions and all the elements tested.
      In the case of glasses containing ZnO, it was shown that the degree of zinc
      migration was linearly related to the mole-% of ZnO in the glass. With respect to
      the durability of glasses, it was shown that the degree of attack increases when
      the degree of silica depolymerisation increases.

PMID- 14967501
TI  - Atmospheric metal deposition in a moss data correlation study with mortality and
      disease in the Netherlands.
AB  - The present paper addresses the correlations between moss metal concentrations
      and epidemiological data on health and mortality rates in The Netherlands.
      Attention was given to both total and fractionated metal concentrations in the
      moss tissues, the latter by factor-analytical (mathematical) approaches, and to
      both grouped and specific diseases. Better than 95% probability correlations were
      found both for total moss elements and mortality due to specific diseases and for
      fractionated moss elements and mortality rates summed for grouped diseases.
      Overall, the presented data suggest that correlation studies between
      biomonitoring data on metal air pollution and (epidemiological) health data may
      prove valuable in turning attention to specific metal-health issues and in
      directing further study into possible dose-response mechanisms in air-associated
      metal epidemiology.

PMID- 14967502
TI  - Reducing the risks of children living near the site of a former lead smeltery.
AB  - The sources of lead exposure, soil, household dust, diet and ambient air near a
      former lead smeltery were studied. The blood lead level of small children was
      also determined. The aim of the study was to define, based primarily on blood
      lead measurements, whether children living in the contaminated area may be at
      risk. Within 500 m from the site of the smeltery, there were several areas where
      the Finnish limit value for soil Pb, i.e. 300 mg/kg, was exceeded. In the
      recently built areas, the surface soil has been replaced and soil remediation has
      taken place in schoolyards and the playgrounds of children's day-care centres.
      Lead content in household dust was clearly elevated in the contaminated areas. In
      approximately 20 years, after the smeltery was closed in 1984, the lead
      concentrations of the fruits and berries in local gardens have decreased to one
      tenth. In some samples, the limit values are still exceeded. The lead
      concentration in ambient air is now 50 times lower than in the 1970s. The blood
      lead level of the children living in the area is slightly but statistically
      significantly higher than that of the children in the control areas. The critical
      blood lead level, i.e. 10 microg/100 ml, was not exceeded in any of the children
      examined. The average and maximum lead concentrations of 63 analysed blood
      samples were 2.2 and 5 microg/100 ml, respectively. In contrast, the average and
      maximum blood lead levels of school children in 1981 were 6.7 and 13.0 microg/100
      ml, respectively. The risk reduction measures undertaken during the past 20 years
      are described.

PMID- 14967503
TI  - Prioritisation of abstraction boreholes at risk from chlorinated solvent
      contamination on the UK Permo-Triassic Sandstone aquifer using a GIS.
AB  - A 250 km2 area of the Permo-Triassic Sandstone aquifer in the West Midlands of
      England, UK, was selected as a test region for the development of a geographic
      information system (GIS)-based risk assessment methodology that incorporates
      contaminant source, groundwater vulnerability and groundwater abstraction
      catchment elements in order to prioritise areas and boreholes potentially at risk
      from chlorinated solvent pollution on a regional scale. Factors incorporated in
      the vulnerability assessment include the nature of soils, presence or absence of
      superficial or glacial deposits, fault density and depth to water table. ARCVIEW
      GIS was employed with a simple ranking system from which the derived
      vulnerability assessment index was combined with current chlorinated solvent user
      industry data and source protection zone components. Results indicate the
      presence of high-risk areas in urban locations where locally dense distributions
      of chlorinated solvent user industries combine with high vulnerability aquifers
      within the catchment of supply boreholes. Ranking of catchment-specific risk
      reveals the abstraction points under greatest stress. The proposed methodology
      has applications as a regional-scale initial screening tool to guide site
      selection for regulatory inspections and assist in prioritising monitoring
      strategies for existing boreholes. Future developments will provide guidance for
      locating new urban boreholes in areas of lowest risk.

PMID- 14967504
TI  - Radon and 'King Solomon's Miners': Faynan Orefield, Jordanian Desert.
AB  - Concentrations of 222Rn were measured in ancient copper mines which exploited the
      Faynan Orefield in the South-Western Jordanian Desert. The concentrations of
      radon gas detected indicate that the ancient metal workers would have been
      exposed to a significant health risk and indicate that any future attempt to
      exploit the copper ores must deal with the hazard identified. Seasonal variations
      in radon concentrations are noted and these are linked to the ventilation of the
      mines. These modern data are used to explore the differential exposure to radon
      and the health of ancient mining communities.

PMID- 14967505
TI  - Impact of natural organic matter (NOM) on freshwater amphipods.
AB  - Natural organic matter (NOM) isolated from the eutrophic Sanctuary Pond (Point
      Pelee National Park, Canada) has an adverse impact on amphipod species (Gammarus
      tigrinus and Chaetogammarus ischnus from Lake Muggelsee, Germany, and
      Eulimnogammarus cyaneus, from Lake Baikal, Russia). Increases in amphipod
      mortality, changes in peroxidase activity and increases of heat shock protein
      (hsp70) expression were observed upon exposure to NOM. The highest resistance to
      the adverse impact of NOM was observed with the endemic Baikalian amphipod E.
      cyaneus. However, the mechanisms behind this finding remains obscure. If
      differences in the sensitivity of the hsp70 antibody may be excluded, different
      modes of action may be postulated: because the adverse impact of NOM may be
      caused by reactive oxygen species (ROS) and the NOM itself, the observed
      differences may be due to the action of ROS alone (with E. cyaneus) and a
      combination of both adverse modes of action (European species).

PMID- 14967506
TI  - Direct and interacting toxicological effects on the waterflea (Daphnia magna) by
      natural organic matter, synthetic humic substances and cypermethrin.
AB  - Humic substances are the main component of dissolved organic matter in all
      aquatic ecosystems, comprising a variety of molecular structures and functional
      groups. They bind organic pollutants and metals, thereby decreasing the
      bioavailability and consequently the toxicity of these substances in most
      instances. Recent studies also describe direct interactions and effects on
      organisms. Current studies also show that in some cases mitigation effects are
      stronger at lower concentrations of natural organic matter (NOM) and that
      toxicity increases with increased NOM concentrations. We hypothetise that at
      higher concentrations the mitigating effects are overlayed by direct effects of
      NOM themselves, thus these aspects were investigated in combination. So, on the
      one hand, this study demonstrates direct effects on toxicological parameters and
      activities of transformation enzyme systems of Daphnia magna, provoked by two NOM
      and one synthetic humic-like substance, HS1500. On the other hand, capacities of
      NOM and synthetic HS1500 to mitigate effects of the insecticide cypermethrin were
      investigated. Taken together, mitigation effects were overlayed by direct own
      effects of the NOM and HS1500. The NOM used were isolates from Suwannee River
      (XAD, Spring 2000) and from streams of the Svartberget forest (reverse osmosis,
      Spring 2000). The HS1500 was synthetically produced by radicalic autoxidation of
      hydroquinones. Suwannee River NOM at concentrations between 50 and 100 mg/l, and
      HS1500 (10-50 mg/l), but not Svartberget NOM increased immobility and lethality
      of the daphnids. All elevated the activity of the soluble glutathione S
      transferase from 0.5 mg/l (HS1500), 1.0 mg/l (Suwannee River NOM) and 10 mg/l
      (Svartberget NOM) onwards, the microsomal glutathione S-transferase did not
      react. The glutathione peroxidase tended to increase. In the single exposure, the
      insecticide cypermethrin increased all toxicological parameters, elevated soluble
      and tendentially microsomal glutathione S-transferase activity between 0.001 and
      1.0 microg/l and tendentially increased glutathione peroxidase. In contrast to
      that, 50 mg/l of the NOM and HS1500 did not mitigate toxicological effects.
      HS1500 in combination with cypermethrin even increased immobility, compared to
      cypermethrin alone. Increase of the NOM or HS1500 concentrations in combination
      with cypermethrin did not increase mitigation as seen in the activity of soluble
      glutathione S-transferases, activities of microsomal glutathione S-transferase
      and glutathione peroxidase even decreased, relative to control, which can be a
      hint of enzyme disfunction or further damages in the cell. An increase of
      concentration did not increase mitigation. Mitigation was higher at lower NOM or
      HS1500 concentration, probably as a consequence of the direct effects caused by
      themselves. Consequently, direct effects are relevant for analysing the
      mitigation qualities.

PMID- 14967507
TI  - Accumulation and lactational transfer of PCBs and pesticides in harbor seals
      (Phoca vitulina) from Svalbard, Norway.
AB  - The harbor seal population on Svalbard, the northernmost breeding site for this
      species, appears to have a truncated age distribution with older animals being
      largely absent. PCBs and pesticides were measured in harbor seal males, females,
      milk and pups from Svalbard to explore whether contaminant exposure or
      accumulation is a possible cause of premature death for these animals. The levels
      and patterns of these contaminants were assessed. In addition, transfer of these
      compounds from females to their pups during lactation was assessed. Both PCB and
      pesticide levels were low compared to more southern harbor seal populations.
      Animals from Svalbard contained 5-10 times lower contaminant levels, compared to
      seals from the Norwegian mainland, and 30 times lower concentrations than those
      of harbor seals from the Gulf of St. Lawrence in eastern Canada. Ringed seals
      from Svalbard have contaminant levels that are comparable to the harbor seals,
      probably because the diet, as well as the metabolic capacity, of the two species
      is similar at this location. The findings of this study indicate that the early
      mortality observed for harbor seals on Svalbard, is not likely to be due to
      contaminant exposure. Female harbor seals transfer a modified contaminant mixture
      to their pups compared to that found within their own tissues; compounds with
      higher log Kow, such as some penta-chlorinated PCBs, were selectively transferred
      into milk. As a result, the contaminant pattern between males and females
      differed, with penta-chlorinated PCBs more abundant in males than in females. In
      addition, pups receive a relatively high amount of the less lipophylic compounds
      and a low amount of the more lipophylic compounds. The similar contaminant
      pattern in milk and pups suggested that they are probably unable to metabolize
      contaminants and consequently, accumulate all ingested chemicals.

PMID- 14967508
TI  - Geographic variation in polychorinated biphenyl and organochlorine pesticide
      concentrations in the blubber of bottlenose dolphins from the US Atlantic coast.
AB  - Concentrations of polychorinated biphenyls (PCBs) and other organochlorine
      contaminants (OCs) were measured in blubber collected from live bottlenose
      dolphins (Tursiops truncatus) at three sites along the United States Atlantic
      coast. Dolphins were sampled via surgical biopsy during capture-release studies
      near Charleston, South Carolina and Beaufort, North Carolina. Additional animals
      were sampled using remote biopsy techniques in estuarine waters near Charleston
      and from the Indian River Lagoon, Florida. Overall concentrations of major
      contaminant groups were found to vary between sites and mean concentrations of
      most OCs from male dolphins in the Indian River Lagoon were less than half of
      those measured from Charleston and Beaufort males. Geometric mean total PCB
      concentrations were 30, 27 and 14 microg/g lipid for male dolphins sampled in
      Beaufort, Charleston and the Indian River Lagoon, respectively. Significant
      variation related to sex- and age-class, as well as geographic sampling location,
      was seen in the PCB congener profiles. The measured PCB concentrations, although
      lower than those reported for stranded animals from the 1987/1988 epizootic along
      the United States mid-Atlantic coast, are sufficiently high to warrant concern
      for the health of dolphins from the sampled populations, particularly the animals
      near Charleston and Beaufort.

PMID- 14967509
TI  - Tree rings as Pb pollution archives? A comparison of 206Pb/207Pb isotope ratios
      in pine and other environmental media.
AB  - Tree rings, if validated as an environmental archive for pollution, would provide
      a convenient, geographically widespread archive for studying the temporal and
      spatial distribution of atmospheric pollutants. We collected tree-ring records
      from Scots pine (Pinus sylvestris L.), ranging in age from 100 to 300 years and
      from one spruce (Picea abies), from sites in southern and northern Sweden and
      analyzed their stable lead isotopic composition (206Pb/207Pb). These results are
      compared to the Pb isotopic composition in soil profiles from each of the sites
      and temporal changes in the 206Pb/207Pb ratio in peat and lake sediment deposits
      in Sweden. The mineral soils at each site are characterized by high 206Pb/207Pb
      ratios (> 1.35), while the ratios in the mor layer are low (1.14-1.16) and
      characterized by atmospheric lead pollution. The 206Pb/207Pb ratios of the tree
      rings, typically approximately 1.18-1.20, indicate a significant (10-30%)
      contribution of Pb derived from the underlying mineral soil. While peat and lake
      sediment records show that the 206Pb/207Pb ratio of atmospheric deposition has
      varied over time, with a pronounced trough between approximately 1930 and 1990,
      the tree rings show no similar trend. Further comparison of published Pb isotope
      data from other tree-ring records with time series from peat bogs and herbarium
      samples also shows poor agreement, and indicates that tree rings always contain a
      mixture of pollution Pb and Pb from the underlying mineral soil. The majority of
      Pb in the wood is derived from atmospheric pollution either directly, through
      aerial interception, or indirectly, through uptake from the large pool of
      accumulated pollution Pb in the soil. Since the Pb isotope ratios of the wood
      indicate that some natural Pb is taken up into the tree, then it must also be
      concluded that some fraction of the pollution Pb in the wood is likewise taken up
      from the forest soil. Based on the Pb isotope analyses, we can only conclude that
      dendrochemical records are not useful in temporal studies of metal pollution.

PMID- 14967510
TI  - Pb contamination and isotopic composition of urban soils in Hong Kong.
AB  - In the urban environment, intense human activities can lead to degradation of
      environmental quality and have potential long-term effects on human health. In
      the present study, Pb contamination of urban soil cores in Hong Kong was
      investigated using a combination of the 'total' concentration, chemical
      partitioning and isotopic composition of Pb in the soils. The analytical results
      showed that urban soil cores in close vicinity to high traffic volumes (> 40000
      vehicles per day) were usually contaminated with Pb, suggesting atmospheric
      deposition of Pb as a consequence of vehicular emissions arising from the
      combustion of leaded gasoline in the past. Increasing Pb concentrations were
      generally associated with decreasing 206Pb/207Pb ratios of the contaminated soil
      cores, offering strong evidence of accumulation of Pb derived from anthropogenic
      sources. In selected contaminated soil cores, the 206Pb/207Pb ratios tended to
      increase in the order: carbonate < exchangeable < Fe-Mn oxide < organic <
      residual fractions. The distribution of the 206Pb/207Pb ratios in the five
      operationally defined chemical fractions showed that the 206Pb/207Pb ratios
      generally increased with increasing stability, demonstrating preferential
      association of anthropogenic Pb with the carbonate, exchangeable, Fe-Mn oxide and
      organic fractions in the soils.

PMID- 14967511
TI  - Cadmium transport in the Lot-Garonne River system (France) - temporal variability
      and a model for flux estimation.
AB  - Fluvial cadmium (Cd) inputs into the Gironde estuary via the Lot-Garonne River
      system were evaluated using nine years of daily measurements of water discharge
      and total suspended sediment content (TSS) combined with monthly analyses of
      dissolved and particulate Cd concentrations. This study demonstrates that
      dissolved and particulate Cd concentrations in the Lot River have strongly
      decreased in the early 1990s. However, dissolved and particulate Cd
      concentrations in the Lot River are still higher than those in the Garonne River.
      In 1992-1998 mean annual Cd concentrations are more or less constant and thus,
      annual Cd fluxes mainly depend on hydrology. Daily total Cd fluxes range from
      0.26 to 966 kg day(-1) in the Lot River and from 0.31 to 1360 kg day(-1) in the
      Garonne River, downstream their confluence. During dry years, Cd fluxes at La
      Reole are dominated by inputs from the upstream Garonne River, whereas during wet
      years they are controlled by inputs from the polluted Lot River watershed. The
      relation between particulate and dissolved Cd fluxes depends on TSS
      concentrations, which appear to be mainly controlled by the succession of floods
      and low waters reflecting short-term basin-scale climate variability. Cadmium
      concentrations, fluxes and the ratio between the particulate and dissolved Cd
      fluxes depends on the absolute value and instantaneous evolution (strong relative
      increase or decrease) of discharge. An empiric model permits deducing intervals
      of daily dissolved Cd fluxes from discharge, hydrological key situation and
      related intervals of 'typical' dissolved Cd concentrations. In 1992-1998 the Lot
      Garonne River system shows close relations between annual dissolved and
      particulate Cd fluxes. These relations allow deducing annual particulate Cd
      fluxes using annual dissolved Cd fluxes obtained from the model. The validation a
      posteriori shows that our empiric model accurately reproduces the annual Cd
      fluxes estimated from the field data with uncertainty lower than 25% for
      dissolved fluxes and lower than 30% for the particulate fluxes. Consequently, the
      empiric model permits estimating annual dissolved and particulate Cd fluxes in
      the Lot-Garonne River system, from daily discharge data, without Cd analysis.
      Cadmium fluxes obtained from the model may be used as approximate values for
      gross fluvial Cd inputs into the Gironde estuary.

PMID- 14967512
TI  - Progressive changes in water and sediment quality in a wetland system for control
      of highway runoff.
AB  - Innovative wetland based systems were designed and installed on the Newbury
      Bypass, Berkshire, England to provide flow balancing and pollution control for
      road runoff. The systems were monitored over 18 months to evaluate performance,
      pollutant removal processes and offer improved design and operation codes for
      this new application of wetlands. Water quality, sediment accumulation rates, and
      metal concentrations in size-fractionated, settling solids and deposited
      sediments were determined in parts of the system to provide information on
      spatial and temporal variability. The results presented here show that over the
      long term, there were progressive changes in parts of the system for BOD and COD
      and for metal concentrations in the sediment fractions, which occurred with
      linear (or semi log-linear) rates, despite variability in flow rates, retention
      times and in pollutant loading to the system. Future work will continue
      monitoring to increase the data set, examine possible processes contributing to
      the regression constants, and test the potential use of the regressions in system
      modelling. Attempts at modelling road runoff treatment using wetlands must allow
      for progressions, since the systems can only be effective if they retain removed
      metals in the sediment sink.

PMID- 14967513
TI  - Chemical properties of urban waste ash produced by open burning on the Jos
      Plateau: implications for agriculture.
AB  - Urban centres produce most of the world's waste and between a third and a half
      goes uncollected. The answer to the problem of waste disposal lies partly in
      agriculture, as waste can be extremely nutrient-rich. In the last decade there
      has been a tremendous increase in the developing world in total city area under
      informal food production and there are many examples of waste recycling onto the
      urban or peri-urban plots. Farmers on the Jos Plateau, Nigeria, have developed a
      successful soil fertility management strategy based on the combination of
      inorganic fertilisers, manure and urban waste ash. This study sought to provide
      some preliminary data on urban waste ash produced by open burning and used in
      farming in a developing country. Ash samples were collected from different
      locations around Jos and tested for C, N, pH, P, Na, K, Ca, Mg, Fe, Mn, Zn, Cu,
      Ni, Cd and Pb. It was found that ash is an effective liming material (because of
      the high pH, and high Ca, Mg and K contents), and has the potential to contribute
      significant quantities of micro-nutrients such as Mn, Zn and Cu. Ash, however, is
      far from being a homogenous material and its variability means that its
      fertilising potential will vary between batches and that, even if mean and median
      levels are low, there is the risk of the formation of localised areas of soil
      with excessive heavy metal contents (this is particularly the case with Pb).
      Further research is required to determine the plant-availability of these
      elements in the ash and to assess the wider environmental and health implications
      of uncontrolled, open burning of waste as a means of producing ash for
      agricultural purposes.

PMID- 14967514
TI  - Mobility of radiocesium in three distinct forest floors.
AB  - The degree of mixing of organic matter with minerals in organic and hemi-organic
      horizons of forest soils largely differs between humus types. As clay minerals
      might control the mobility of radiocesium in these forest floor horizons, plant
      contamination could greatly vary with the kind of humus. We measured the mobility
      of radiocesium in the upper O, OAh and Ah horizons of three acid forest soils
      with three distinct humus types: eumoder, dysmoder and fibrimor. We used two
      different approaches: a physico-chemical test quantifying the radiocesium
      interception potential (RIP) and a biological assay simulating an experimental
      rhizosphere. The results show that the (137)Cs horizon-to-plant transfer is
      directly governed by RIP, and thus by frayed edge sites born by weathered
      micaceous minerals. The inverse relationship between RIP and organic matter
      content indicates that in the three sites investigated the mixing of organic
      residues with Cs-fixing minerals is a key process in 137Cs mobility. These Cs
      fixing clay minerals indeed decrease in the sequence eumoder > dysmoder >
      fibrimor because they are more diluted in forest floor with less bioturbation.
      Our results suggest that humus type might be an important parameter in
      classifying forest soils with respect to their ability to transfer radiocesium to
      the above standing vegetation.

PMID- 14967515
TI  - Trends of radionuclide sorption by estuarine sediments. Experimental studies
      using 133Ba as a tracer.
AB  - Sediments play an important (but still poorly understood) role in the dispersion
      and final fate of radionuclides and other hazardous materials in aquatic systems.
      Adopting an experimental point of view, the present work deals with the transfer
      of a radioactive tracer from water to sediments. Sediments and waters were
      sampled in the Odiel and Tinto estuaries (South-West Spain) with anthropogenic
      enhanced 226Ra concentrations. 133Ba was used as a tracer since it is a gamma
      emitter and a good analogue of the environmental behaviour of 226Ra. Laboratory
      experiments have been carried out to quantify the uptake kinetics of 133Ba by
      sediments in aqueous suspensions and by sediment cores under a water column at
      rest. Depth distributions of 133Ba in sediments have been studied with different
      contact times and using sediment samples with different grain sizes. The results
      reveal an important and fast uptake by suspended sediments (up to 40% in 10 min
      with a 20 g l(-1) suspension) and sediment cores (up to 70% in a few minutes).
      The kinetics of the uptake by suspended sediments could be reasonably described
      by a model of two parallel and reversible reactions followed by a weakly
      reversible reaction. The total uptake and the rate of reaction decreased with the
      increment of grain size. Furthermore, uptake following diffusion through the
      interstitial water was hardly detectable beyond 1 cm depth. For the case with
      more experimental results, the depth distribution could be reasonably described
      by the analytical solution based on the use of an effective diffusion coefficient
      (4.2 x 10(-12) m2 s(-1)) and the measured intrinsic distribution coefficient (kd
      = 63 +/- 6 l kg(-1)).

PMID- 14967516
TI  - Monitoring of the antioxidant BHT and its metabolite BHT-CHO in German river
      water and ground water.
AB  - The behavior of anthropogenic polar organic compounds in ground water during
      infiltration of river water to ground water was studied at the Oderbruch area on
      the eastern border of Germany. Additionally, waste water sewage treatment works
      (STWs) discharging their treated waste water into the Oder River and rain water
      precipitation from the Oderbruch area were investigated. The study was carried
      out from March 2000 to July 2001 to investigate seasonal variations of the target
      analytes. Samples were collected from four sites along the Oder River, from 24
      ground water monitoring wells located close to the Oder, from one rain water
      collection station, from two roof runoffs, and from four STWs upstream of the
      Oderbruch. Results of the investigations of the antioxidant 3,5-di-tert-butyl-4
      hydroxy-toluene (BHT) and its degradation product 3,5-di-tert-butyl-4-hydroxy
      benzaldehyde (BHT-CHO) are presented. BHT and BHT-CHO were detected in all
      samples of the Oder River with mean concentrations of 178 and 102 ngl(-1),
      respectively. BHT and BHT-CHO were also detected in effluent waste water samples
      from municipal STWs at mean concentrations of 132 and 70 ngl(-1), respectively.
      Both compounds are discharged into river water directly via treated waste water.
      In the rain water sample, 308 ngl(-1) of BHT and 155 ngl(-1) of BHT-CHO were
      measured. Both compounds were detected in roof runoff with mean concentrations of
      92 ngl(-1) for BHT and 138 ngl(-1) for BHT-CHO. The median values of BHT and BHT
      CHO in ground water samples were 132 and 84 ngl(-1), respectively. The chemical
      composition of ground water from parts of the aquifer located less than 4.5 m
      distant from the river are greatly influenced by bank filtration. However, wet
      deposition followed by seepage of rain water into the aquifer is also a source of
      BHT and BHT-CHO in ground water.

PMID- 14967517
TI  - Effects of genotoxic compounds on DNA and development of early and late grass
      shrimp embryo stages.
AB  - Early and late developmental stages of grass shrimp embryos were exposed to
      different concentrations of two genotoxicants, 2-methyl-1,4-naphthoquinone (MNQ)
      and 4-nitroquinoline-N-oxide (NQO). DNA strand breaks were assessed by the comet
      assay while embryo development effects were determined by % of embryos hatching.
      Early embryo stage embryos were significantly more sensitive to genotoxicants
      than late stages. For example, all stage 4 embryos failed to hatch at 1 microM
      NQO while 95% of stage 8 hatched at this concentration. High DNA tail moments,
      which are a measure of the number of DNA strand breaks, were found in late stage
      embryos exposed to genotoxicants. Early stage embryo development was effected by
      low concentrations of genotoxicants but no changes were observed in DNA tail
      moments. We suggest that high DNA moments in late embryo stages reflect high DNA
      repair activity, while early stages may lack a fully developed DNA repair system.

PMID- 14967518
TI  - Effect of biodeposits from mussel culture on macroinvertebrate assemblages at
      sites of different hydrodynamic regime.
AB  - The present study examined for differences in macroinvertebrate assemblage
      composition inside and outside of mussel farm sites experiencing different
      hydrodynamic regimes. Multivariate analysis revealed that there were significant
      differences in macroinvertebrate assemblage composition (averaged across seasons)
      between samples taken inside and outside of the two relatively low energy sites,
      whilst no such difference was observed for the relatively high energy site. Taxa
      that best discriminated between the dissimilarities observed in macroinvertebrate
      assemblage composition inside and outside farms were principally polychaetes
      (more abundant inside) and ophiuroids (more abundant outside). Sediment total
      organic matter and number of mussel shells were the parameters that best
      explained the difference in macroinvertebrate assemblage observed at the two
      relatively sheltered farm study sites. No taxa or environmental variables were
      particularly good at discriminating or explaining differences observed inside and
      outside the relatively high energy farm site. The present study indicates there
      is a relationship between the hydrodynamic regime of a farm site, organic
      enrichment of seabed sediments by mussel biodeposits, and a subsequent
      modification of the macroinverebrate assemblages. This finding has implications
      for the site selection of mussel farms in coastal environments.

PMID- 14967519
TI  - Restoration of oiled mussel beds in Prince William Sound, Alaska.
AB  - Natural loss of hydrocarbons was often low from mussel (Mytilus trossulus) beds
      (which were typically not cleaned after the Exxon Valdez oil spill), thus this
      habitat remained a long-term source of oil. Consequently, experimental
      restoration of nine contaminated beds was attempted in 1994; mussels were
      removed, contaminated surface sediment was replaced (33 metric tons), and
      original mussels were returned. Hydrocarbon concentrations and mussel populations
      were monitored for 5 years thereafter. Post-restoration mussel population
      fluctuations were indistinguishable from regional changes. Increased short-term
      oil loss was apparent, but long-term (5 year) improvement was equivocal and
      difficult to distinguish from natural losses. By 1999, oil concentrations in
      mussels were typically at baseline levels in restored and oiled reference beds;
      concentrations in replaced sediment were elevated in one third of restored beds,
      indicating recontamination from underlying or surrounding sediment. Our results
      suggest mussel relocation is feasible but suggest oil might more effectively be
      removed from sediment mechanically or chemically than manually.

PMID- 14967520
TI  - Differential gene expression in mummichogs (Fundulus heteroclitus) following
      treatment with pyrene: comparison to a creosote contaminated site.
AB  - Mummichogs, Fundulus heteroclitus, an estuarine fish with a relatively small home
      range found along the eastern coast of the United States are well-suited to
      monitoring contaminant effects, including those of polycyclic aromatic
      hydrocarbons (PAHs). One of the common PAHs in estuaries is pyrene. We report
      here on efforts to develop multiple biomarkers of pyrene exposure in this
      species. Adult male mummichogs were exposed in the laboratory to the weak aryl
      hydrocarbon receptor (AhR) agonist pyrene at 0, 30, or 50 microg/L in 7-day
      static renewal exposures. The RNA was extracted from livers and alterations in
      mRNA expression were assessed by subtractive hybridization and differential
      display in order to produce multiple biomarkers of pyrene exposure. Genes
      demonstrating differential expression were confirmed by quantitative-PCR (Q-PCR)
      and include cytochrome P-450 1A (CYP1A), a putative hepatocyte growth factor
      activator, a X-ray inducible retrotransposon, and several expressed sequenced
      tags (ESTs). Some of these genes represent new biomarkers of pyrene exposure and
      potential biomarkers of PAH exposure. Therefore, similar changes were
      investigated at a Superfund site in Charleston, SC. Mummichogs from a creosote
      contaminated site and from a reference site (North Inlet National Estuarine
      Research Reserve near Georgetown, SC) were trapped, RNA extracted from the
      livers, and Q-PCR performed. Many of the genes differentially expressed following
      pyrene exposure were not altered at the creosote contaminated site in comparison
      to the reference site. However, CYP1A and an EST were induced. CYP1A induction at
      Diesel Creek indicates that this population of fish does not demonstrate
      refractory CYP1A phenotypes observed at several sites with high levels of AhR
      agonists. Ultimately, we anticipate that the use of multiple biomarkers of PAH
      exposure will provide useful information on the potential effects of toxicants.

PMID- 14967521
TI  - Butyltin concentrations along the Japanese coast from 1997 to 1999 monitored by
      Caprella spp. (Crustacea: Amphipoda).
AB  - The concentrations of butyltins along the Japanese coastline were investigated
      from 1997 to 1999, 7 to 9 years after implementation of legislation limiting the
      use of tributyltin (TBT) in Japan. Seawater was sampled at 0.5 m depth, and
      Caprella spp. were collected from Sargassum spp. and aquaculture facilities from
      18 areas within four broad areas along the coastline of Japan, i.e., the Pacific
      coast of northern Japan, the coast along the Sea of Japan, Tokyo Bay and adjacent
      areas, and western Japan. Butyltins (MBT, DBT and TBT) were detected in 32 of the
      63 seawater samples with average concentrations of 4.6 ng MBT/l, 4.5 ng DBT/l and
      6.8 ng TBT/l, respectively. Butyltin concentrations in seawater from western
      Japan indicate "hot spots" even in unpopulated areas. Butyltins (MBT, DBT and
      TBT) were detected in all samples of Caprella spp., varying from 2.3 ng BTs /g
      wet wt in C. penantis R-type from Tobishima Island in the Sea of Japan to 464 ng
      BTs /g wet wt in C. decipiens Mayer from Amakusa, western Kyushu. The BT
      concentrations in Caprella spp. form western Japan were significantly higher than
      those from other areas, including Tokyo Bay and adjacent areas, where large scale
      industry and international ports are located. These results indicate that
      butyltin contamination still remains even in unpopulated areas after the
      regulation on TBT usage, and that the regulation governing TBT usage since 1990
      has not been effective enough to concede recovery of shallow water ecosystems
      around Japan.

PMID- 14967522
TI  - Single molecular mechanics of a cholesterol-bearing pullulan nanogel at the
      hydrophobic interfaces.
AB  - The study of nanogel (hydrogel nanoparticle) has intensified in the last decade
      due to the enormous potential applications in biomimetics, biosensors, artificial
      muscles and drug delivery (or release) systems. Cholesterol-bearing pullulan
      (CHP) is composed of hydrophilic pullulan backbone and partly substituted
      hydrophobic cholesterol, and is capable of forming a stable hydrogel nanoparticle
      in aqueous solution due to the self-assembly of hydrophobic cholesterol moieties.
      The conformation of CHP changes dramatically at the hydrophobic interfaces. In
      order to understand the interfacial responses of CHP, the interaction forces of
      CHP nanogels to the hydrophobic HOPG (highly orientated pyrolytic graphite) or
      carbon-coated surfaces were measured using atomic force microscope. The freely
      jointed china model for CHP molecular elasticity was applied to the force
      extension curves and debonding force-pull-off distance in order to estimate the
      contour lengths and the segment lengths of the CHP molecules. The segment length
      of CHP chains in aqueous solution was estimated 0.32+/-0.19 nm showing a very
      flexible chain. From our analysis of the dynamic force measurements, the
      debonding forces were shown to depend on the applied loading forces. The zero
      kinetic off-rate K(off)(0) and the transition state x(b) were estimated to be 1.1
      x 10(-3)s(-1) and 2.9A, respectively.

PMID- 14967523
TI  - Sol-gel derived fluor-hydroxyapatite biocoatings on zirconia substrate.
AB  - Fluor-hydroxyapatite (FHA) film was coated on a zirconia (ZrO(2)) substrate by a
      sol-gel method. An appropriate amount of F ions was incorporated into the
      hydroxyapatite (HA) during the preparation of the sols. The apatite phase began
      to crystallize after heat treatment at 400 degrees C, and increased in intensity
      above 500 degrees C. No decomposition was detected by X-ray diffraction analyses
      up to 800 degrees C, which illustrates the high thermal stability of the FHA
      films. The films showed a uniform and dense morphology with a thickness of
      approximately 1 microm after a precisely controlled heat treatment process. These
      FHA films adhered firmly to the zirconia substrate, representing notable adhesion
      strengths of approximately 70 MPa after heat treatment above 500 degrees C. The
      dissolution rate of the FHA coating layer varied according to the heat treatment
      temperature, which was closely related to the film crystallinity. The dissolution
      rate of the FHA film was lower than that of the HA film, suggesting the
      possibility of a functional gradient coating of HA and FHA. The MG63 cells seeded
      onto the FHA films proliferated in a similar manner to those seeded onto pure HA
      ceramic and a plastic control.

PMID- 14967524
TI  - Interaction of hydroxyapatite-titanium at elevated temperature in vacuum
      environment.
AB  - In this study, the interaction between hydroxyapatite (HA) and titanium (Ti) at
      elevated temperature in vacuum environment was investigated. The 80 wt% HA-20 wt%
      Ti powder mixtures and 90 wt% HA-10 wt% Ti powder mixtures were dry pressed and
      heat-treated at 1100 degrees C in vacuum environment. HA powders and the
      commercially pure Ti powders were used as controls. The heat-treated samples were
      characterized using X-ray diffraction (XRD), Fourier transform infrared
      spectroscopy, scanning electron microscope (SEM) and energy disperse spectra. XRD
      and SEM indicated densification of metallic Ti specimens during the in-vacuum
      heat treatment. Heat treatment of HA specimens in vacuum resulted in the loss of
      hydroxyl groups as well the formation of a secondary beta-tricalcium phosphate
      phase. Metallic Ti was not observed in the in-vacuum heat-treated HA-Ti
      specimens. However, alpha-tricalcium phosphate, tetracalcium phosphate and
      calcium titanium oxide were observed for the in-vacuum heat-treated HA-Ti
      specimens. It was concluded that the in-vacuum heat-treatment process completely
      converted the metal-ceramics composites to ceramic composites.

PMID- 14967525
TI  - Preparation of novel mesoporous carbons for the adsorption of an inflammatory
      cytokine (IL-1 beta).
AB  - Mesoporous carbons derived from two types of sulphonated styrene divinylbenzene
      copolymers (Macronet MN500HS and CT275, Purolite International Ltd) were produced
      and their adsorptive capacity for the proinflammatory cytokine IL-1 beta (MW 14.4
      kDa) determined. The carbons produced had surface areas from 400 to 1200 m(2)g(
      1) and pore volume between 0.2 and 1.4 cm(3)g(-1). The mechanical strength of the
      carbon beads with surface area values up to 800 m(2)g(-1) were robust. The
      highest adsorption value of IL-1 beta was 150 ng g(-1) for a mesoporous carbon
      with surface area around 900 m(2)g(-1) and pore volume around 1.3 cm(3)g(-1).
      However, there was a trade-off between adsorptive capacity and mechanical
      strength. When used in conjunction with existing treatment modalities, the
      materials produced have the potential to enhance the removal of uraemic toxins.

PMID- 14967526
TI  - The effect of ionic products from bioactive glass dissolution on osteoblast
      proliferation and collagen production.
AB  - Bioactive ceramics developed during the past few decades have interesting
      properties from the biological standpoint, but their effects on cellular events
      remain partially unknown. In the current work, we investigated cellular
      viability, proliferation, morphology changes and metabolic activity of rat
      primary culture osteoblasts in contact with the ionic products from the
      dissolution of a bioactive glass with 60% of silica (BG60S) and a biphasic
      calcium phosphate (BCP). We observed that although osteoblasts cultured with
      BG60S showed vacuole formation, cell viability was increased when compared to BCP
      and control. The vacuole formation was not due to the presence of high calcium
      concentration in the ionic products from the dissolution of BG60S and was not
      related to nitric oxide production from the osteoblasts. We did find that high
      silicon concentration could induce cellular vacuole formation. Additionally,
      energy dispersive spectroscopy analysis indicated that vacuole contained 75% more
      silicon than other regions in the cell outside the vacuole. We further found that
      collagen production was higher in osteoblast cultured in the presence of BG60S
      compared to BCP and control, while alkaline phosphatase production was similar
      among cells incubated with BG60S, BCP and control. Together, our results indicate
      that osteoblast vacuole formation was due to high silicon contents in the
      dissolution of BG60S and we can suggest that despite the vacuole formation, there
      is no significant alteration in the bioceramic cell interaction.

PMID- 14967527
TI  - Proliferation and bone-related gene expression of osteoblasts grown on
      hydroxyapatite ceramics sintered at different temperature.
AB  - Human osteoblast-like cells SaOS-2 (ATCC HTB85) were seeded onto three kinds of
      hydroxyapatite (HA) ceramics sintered at different temperature (1200 degrees C,
      1000 degrees C and 800 degrees C). Scanning electron microscopy (SEM) was
      conducted to detect the surface microstructure. Cells were cultured on these
      substrates for 6 and 12 days and cell proliferation rate and mRNA expression for
      osteocalcin, osteonectin, type I collagen and alkaline phosphatase and protein
      production for osteocalcin, bone sialoprotein and osteonectin were detected with
      quantitative in situ hybridization and immunocytochemistry techniques. SEM
      revealed that crystal particle size was affected by sintering temperature. Result
      showed that cell proliferation rate on HA ceramics sintered at 1200 degrees C was
      the highest. Osteonectin and type I collagen mRNA expression was not altered by
      sintering temperature. After 12 days in culture, bone sialoprotein, osteocalcin
      and osteonectin proteins levels were significantly (p<0.05) higher when SaOS-2
      cells were cultured on HA sintered at 1200 degrees C, compared to the other two
      surfaces, suggesting that HA sintered at high temperature may be a better
      candidate for in vivo implantation. This result provides valuable information
      concerning the clinic application of HA ceramics sintered at different
      temperature.

PMID- 14967528
TI  - Osseointegration of a hydroxyapatite-coated multilayered mesh stem.
AB  - A new type of porous coating for hip prostheses called "multilayered mesh" was
      tested under weight-bearing conditions. The surface of the stem is constructed of
      titanium mesh produced by etching. The hip stems of hydroxyapatite (HA)-coated
      multilayered mesh and conventional beads were implanted into canine right hips,
      and animals were killed 3, 6 and 10 weeks and 6 and 12 months after implantation.
      Shear strength between the implant and the bone was evaluated by the push-out
      test. Bone ingrowth was calculated from backscattered electron imaging-scanning
      electron microscopy (BEI-SEM) images of transverse sections. Toluidine blue
      stained sections and the BEI-SEM images were evaluated histologically. The break
      sites of the specimens after the push-out test were evaluated on BEI-SEM images
      of longitudinal sections. The mean push-out strength of the HA-coated
      multilayered mesh samples was greater than that of the beads-coated samples every
      time tested, and the HA-coated multilayered mesh implants had significantly
      stronger push-out strength at 3 and 6 weeks (p<0.05). The strength of the HA
      coated multilayered mesh implants was even greater at 6 and 12 months, whereas
      the strength of the beads-coated samples decreased. The HA-coated multilayered
      mesh implants showed significantly higher percentages of bone ingrowth than the
      beads-coated implants every time tested, except at 6 months (p<0.05). At 6 and 12
      months, the bone ingrowth data for the HA-coated multilayered mesh implants
      increased, whereas it decreased for the beads-coated implants. The new bone
      formation had reached the bottom of the porous area of the HA-coated multilayered
      mesh surface by 3 weeks, but not had reached the bottom of the conventional beads
      surface. At 6 and 12 months, the smaller pores of the bead surface stopped the
      thickening of trabecular bone, and at 12 months, the break sites were at the bone
      implant interface of the bead surface, whereas they were on the bone side of the
      HA-coated multilayered mesh surface. The difference between the break sites was
      significant at 12 months (p<0.05). The HA-coated multilayered mesh stem provided
      faster, stronger, and more durable osseointegration than the conventional bead
      stem.

PMID- 14967529
TI  - Synthesis and characterization of acrylic terpolymers with RGD peptides for
      biomedical applications.
AB  - The goal of this research was to design a biomaterial, using acrylic terpolymers,
      which could support endothelial cells and function in small diameter vascular
      graft applications. Hexyl methacrylate (HMA) and octyl methacrylate (OMA) were
      used as comonomers to produce a material with a low glass transition temperature
      (T(g)). Methacrylic acid (MAA) was used to provide ionic character, and methyl
      methacrylate (MMA) was selected because of its wide usage in biomedical
      applications. Cation neutralization was employed to modify the mechanical
      properties. RGD-based peptide sequences were attached to promote endothelial cell
      adhesion, because vascular grafts seeded with endothelial cells have fewer
      problems with thrombosis. The two methods used to incorporate peptide sequences
      were a chain transfer reaction during polymerization, and a coupling reaction
      attaching the peptides to carboxyl groups on the polymer after polymerization.
      The compositions that produced T(g)s of approximately 0 degrees C were 75 mol%
      OMA and 92 mol% HMA. The Young's modulus of the HMA copolymer was approximately
      0.37 MPa, well below the desired value of 0.9 MPa. Likewise, the Young's modulus
      of approximately 0.50 MPa for the OMA copolymer was also below the desired value.
      After partial neutralization with sodium cations, the Young's moduli increased to
      approximately 0.93 and 0.99 MPa, respectively. The chain transfer reaction
      lowered the molecular weights and mechanical properties of the copolymers, while
      the coupling reaction method had little effect on these properties. The chain
      transfer method appears to be a promising one-step method to produce polymers
      with a wide range of peptide concentrations.

PMID- 14967530
TI  - Smooth muscle-like tissues engineered with bone marrow stromal cells.
AB  - Bone marrow-derived cells have demonstrated the ability to differentiate into
      multiple mesenchymal cell lineages. Here we tested whether smooth muscle (SM)
      like tissues can be created in vivo with bone marrow stromal cells (BMSCs).
      Cultured canine BMSCs, which expressed SM cell-specific markers including SM
      alpha-actin and SM myosin heavy chain, were seeded on three-dimensional,
      biodegradable polymer scaffolds and implanted into peritoneal cavity of athymic
      mice. The cell-scaffold constructs retrieved 4 weeks after implantation formed
      three-dimensional tissues. Immunohistochemical analyses showed that the tissue
      reconstructs expressed SM alpha-actin and SM myosin heavy chain. Masson's
      trichrome staining showed the presence of significant amounts of collagen in the
      tissue reconstructs. Cells labeled with a fluorescent tracer prior to
      implantation were still present in the tissue reconstructs 4 weeks after
      implantation. Non-seeded scaffolds (control groups) retrieved 4 weeks after
      implantation did not exhibit extensive tissue formation. This study demonstrates
      the potential of BMSCs as an alternative cell source for tissue engineering of
      SM.

PMID- 14967531
TI  - The use of PEGT/PBT as a dermal scaffold for skin tissue engineering.
AB  - Human skin equivalents (HSEs) were engineered using biodegradable-segmented
      copolymer PEGT/PBT as a dermal scaffold. As control groups, fibroblast-populated
      de-epidermized dermis, collagen, fibrin and hybrid PEGT/PBT-collagen matrices
      were used. Two different approaches were used to generate full-thickness HSE. In
      the 1-step approach, keratinocytes were seeded onto the fibroblast-populated
      scaffolds and cultured at the air-liquid (A/L) interface. In the 2-step approach,
      fully differentiated epidermal sheets were transferred onto fibroblast-populated
      scaffolds and cultured at the A/L. In a 1-step procedure, keratinocytes migrated
      into the porous PEGT/PBT scaffold. This was prevented by incorporating fibroblast
      populated collagen into the pores of the PEGT/PBT matrix or using the 2-step
      procedure. Under all experimental conditions, fully differentiated stratified
      epidermis and basement membrane was formed. Differences in K6, K16, K17, collagen
      type VII, laminin 5 and nidogen staining were observed. In HSE generated with
      PEGT/PBT, the expression of these keratins was higher, and the deposition of
      collagen type VII, laminin 5 and nidogen at the epidermal/matrix junction was
      retarded compared to control HSEs. Our results illustrate that the copolymer
      PEGT/PBT is a suitable scaffold for the 2-step procedure, whereas the
      incorporation of fibroblast-populated collagen or fibrin into the pores of the
      scaffold is required for the 1-step procedure.

PMID- 14967532
TI  - Enhanced biological stability of collagen porous scaffolds by using amino acids
      as novel cross-linking bridges.
AB  - Collagen porous scaffolds have been widely employed as a dermal equivalent to
      induce fibroblasts infiltration and dermal regeneration. To eliminate the
      disadvantageous drawback of the fast degradation speed, a cross-linking method
      was adopted by using a water-soluble carbodiimide, 1-ethyl-3-(3
      dimethylaminopropyl)-carbodiimide (EDAC) and N-hydroxysuccinimide (NHS) in the
      presence of amino acids (glycin, glutamic acid or lysine), which function as
      cross-linking bridge between collagen molecular chains. In vitro assessment of
      the biological stability of the cross-linked collagen scaffolds found that the
      collagenase biodegradation degree was greatly decreased when lysine was added,
      resulting in a more biological stable scaffold. On the other hand, the
      biodegradation degree was accelerated compared with the purely cross-linked when
      glutamic acid was added, while less influenced by glycin addition. By comparing
      the biodegradation degree of the scaffolds added with amino acids and their model
      compounds, i.e. adipic acid and hexane diamine, the key factor influencing the
      biological stability was further investigated. The results indicated that the
      crucial factor is dependent on the ratio of amino groups to carboxyl groups in
      the cross-linking system. At optimal ratio the lowest biodegradation degree is
      achieved. Scanning electron microscopy measurements prove that the three
      dimensional structure of the scaffolds was largely preserved. Preliminary in
      vitro culture of fibroblasts in the collagen scaffold cross-linked with EDAC/NHS
      in the presence of lysine has shown that the original good cytocompatibility of
      collagen was retained.

PMID- 14967533
TI  - A rapid temperature-responsive sol-gel reversible poly(N-isopropylacrylamide)-g
      methylcellulose copolymer hydrogel.
AB  - Poly(N-isopropylacrylamide) (PNIPAAm) was grafted to methylcellulose (MC) with
      various feeding ratios using ammonium persulfate and N,N,N',N'-tetramethyl
      ethylene diamine as an initiator. FTIR results confirm the formation of PNIPAAm-g
      MC copolymers. The temperature responsiveness of copolymer gels was investigated
      by turbidimetry, dynamic contact angle (DCA), differential scanning calorimetry
      and dynamic mechanical analysis (DMA). The results indicate that PNIPAAm-g-MC
      hydrogels are strongly temperature responsive. At lower contents of MC, the lower
      critical solution temperature (LCST) is decreased, whereas further increasing MC
      contents raises the LCSTs. It is observed that the phase transition of the
      hydrogels occurs reversibly within 1 min, and near body temperature, a rigid gel
      can be generated in a certain range of MC content. What is more, the
      incorporation of MC prevents the syneresis of copolymer hydrogel. DMA measurement
      reveals that the storage moduli (E') of the gels increase upon increasing MC
      contents, and moreover the values of E' go up markedly above LCST. The copolymer
      hydrogels hold a promise as a blood vessel barrier by tuning gelation
      temperature, gelation time and mechanical strength.

PMID- 14967534
TI  - PDLLA/Bioglass composites for soft-tissue and hard-tissue engineering: an in
      vitro cell biology assessment.
AB  - The aim of this study was to examine the effect of increased content of 45S5
      Bioglass (0-40 wt%) in poly(dl-lactic acid) (PDLLA) porous foams on the behaviour
      of MG-63 (human osteosarcoma cell line) and A549 cells (human lung carcinoma cell
      line). The ability of these cell lines to grow on bioactive composites was
      quantitatively investigated in order to assess the potentiality for their use in
      hard and soft-tissue engineering. Two hours after cell seeding, an increase of
      cell adhesion according to the increased content of Bioglass((R)) present in the
      foams for both cell types was observed. Cell proliferation studies performed over
      a period of 4 weeks showed a better aptitude of the A549 cells to proliferate on
      PDLLA foams containing 5 wt% Bioglass when compared to the proliferation on foams
      with 40 wt% Bioglass. A lower proliferation rate was obtained for cells on pure
      PDLLA. Scanning electron microscopy analysis showed for both cell types the
      presence of cells inside the porous structure of the foams. These results
      confirmed the biocompatibility of PDLLA/Bioglass composite foams and the positive
      effect of Bioglass on MG-63 cell behaviour and also showed for the first time the
      possibility for human lung epithelial type II cells to adhere and proliferate on
      these porous scaffolds. In addition, we describe a positive effect of 45S5
      Bioglass on A549 cell behaviour in a dose-dependent manner, indicating the
      potential of using PDLLA/Bioglass composites with an optimal concentration of
      45S5 Bioglass not only in bone tissue engineering but also in lung tissue
      engineering.

PMID- 14967535
TI  - The effect of hydrogel charge density on cell attachment.
AB  - The competitive growth patterns of osteoblasts and fibroblasts can determine if
      healthy bone or pathologic scar tissue is formed at a wound site. Cell
      interactions with various alloplastic biomaterials used for tissue-engineering
      applications is complex. Defined synthetic mediums are valuable for studying
      ionic and cell receptor-specific interactions. The objectives of this study were
      to determine if fibroblasts and osteoblasts differentially attached to HEMA and
      PEG hydrogels copolymerized with positive, negative, or neutral charge densities,
      or when grafted with specific integrin receptor RGD adhesion ligand. Cytoskeletal
      phenotypes were assessed with immunofluorescent microscopy and cell attachment
      assays. Osteoblast cell attachment to both HEMA and PEG hydrogels was
      significantly higher (P<0.01) as compared to fibroblast cells. Positively charged
      HEMA and PEG hydrogels supported the greatest cell attachment, followed by RGD
      grafted, negative, and neutral charge densities, respectively. Each of these
      conditions elicited nearly a two-fold increase in osteoblast cell attachment, as
      compared to fibroblasts. Cell attachment to serum-coated coverslips was used as
      the control. Immunofluorescent analysis showed that both cell types attached and
      spread better on the positively charged hydrogels. However, fibroblasts
      demonstrated less spreading as compared to osteoblasts. In conclusion,
      differences in hydrophilic properties differentially affect osteoblast and
      fibroblast cell attachment and spreading.

PMID- 14967536
TI  - Lactoferrin and ceruloplasmin derivatized superparamagnetic iron oxide
      nanoparticles for targeting cell surface receptors.
AB  - Tissue and cell-specific drug targeting can be achieved by employing nanoparticle
      coatings or carrier-drug conjugates that contain a ligand recognized by a
      receptor on the target cell. Superparamagnetic iron oxide nanoparticles have been
      used for many years in various biomedical applications. In this study,
      superparamagnetic nanoparticles with specific shape and size have been prepared
      and coupled to various proteins. These particles are characterized in vitro and
      their influence on human dermal fibroblasts is assessed in terms of cell
      adhesion, viability, morphology and cytoskeleton organization using various
      techniques to observe cell-nanoparticle interaction, including light,
      fluorescence, scanning and transmission electron microscopy. The results showed
      that each nanoparticle type with different surface characteristics caused a
      distinctly different cell response. The underivatized magnetic particles were
      internalized by the fibroblasts probably due to endocytosis, which resulted in
      disruption of the cell membrane and disorganized cell cytoskeleton. In
      contradiction, lactoferrin or ceruloplasmin coated nanoparticles attached to the
      cell membrane, most likely to the cell expressed receptors and were not
      endocytosed. One major problem with uncoated magnetic nanoparticles has been the
      endocytosis of particles leading to irreversible entry. These experiments provide
      a route to prevent this problem, suggesting that cell response can be directed
      via specifically engineered particle surfaces.

PMID- 14967537
TI  - Pharmacodynamic-pharmacokinetic profiles of metformin hydrochloride from a
      mucoadhesive formulation of a polysaccharide with antidiabetic property in
      streptozotocin-induced diabetic rat models.
AB  - The antidiabetic property of a formulation containing metformin hydrochloride and
      detarium gum has been evaluated in streptozotocin model of experimental rats.
      Both the gum and metformin hydrochloride possess antidiabetic properties to
      varying degrees. The pharmacokinetics of metformin from the mucoadhesive dosage
      forms indicated that for metformin alone, the area under the curve (AUC) values
      were 125.6 and 135.6 mgh/ml at 200 and 400 mg/kg BW, respectively. For the
      mucoadhesive products using the same dose levels, the AUCs were modified to 102.4
      and 150.2 in detarium gum and 59.9 and 80.4 in NaCMC. The results indicate that
      detarium gum is a good excipient for the formulation of metformin mucoadhesive
      delivery systems when compared with NaCMC. The gum also showed promising
      antidiabetic effect and should be cautiously used as it may lead to depressed
      blood-glucose levels beyond the desired levels.

PMID- 14967538
TI  - Conjugation of amino-containing drugs to polysaccharides by tosylation:
      amphotericin B-arabinogalactan conjugates.
AB  - The coupling of amphotericin-B (AmB), a water-insoluble antifungal and
      antileishmanial agent, to arabinogalactan (AG) via tosylate or mesylate
      derivatives was investigated as a method for the conjugation of amino-containing
      drugs to polysaccharides. In the first step, AG was reacted with tosyl- or mesyl
      chloride at different ratios to obtain tosylate or mesylate AG derivatives. AmB
      was conjugated to AG derivatives in either aqueous or organic media via an amine
      bond. AG-AmB conjugates were soluble in water and exhibited improved stability in
      aqueous solutions as compared to the unbound drug. The conjugates showed
      comparable inhibitory concentration values against the pathogenic yeast Candida
      albicans, and against Leishmania major parasites. They were about 60 times less
      hemolytic against sheep erythrocytes than the free drug, and less toxic when
      injected i.v. to BALB/c mice.

PMID- 14967539
TI  - Layered double hydroxide as an efficient drug reservoir for folate derivatives.
AB  - Folic acid derivatives such as folinic acid and methotrexate (MTX) have been
      successfully hybridized with layered double hydroxide (LDH) by ion-exchange
      reaction. The X-ray diffraction patterns and spectroscopic analyses indicate that
      these molecules intercalated into the hydroxide interlayer space are stabilized
      in the tilted longitudinal monolayer mode by electrostatic interaction. No
      significant changes in their structural and functional properties are found in
      the hybrids. The cellular uptake test of MTX-LDH hybrid is carried out in the
      fibroblast (human tendon) and SaOS-2 cell line (Osteosarcoma, human) by in vitro
      MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide) assay. The
      initial proliferation of SaOS-2 cell is more strongly suppressed by treatment
      with MTX-LDH hybrid than with MTX alone. This study clearly shows that LDH not
      only plays a role as a biocompatible-delivery matrix for drugs but also
      facilitates a significant increase in the delivery efficiency.

PMID- 14967540
TI  - Specific role of polysorbate 80 coating on the targeting of nanoparticles to the
      brain.
AB  - It was reported that nanoparticles with polysorbate 80 (Tween 80, T-80) coating
      represented tools used for delivering drugs to brain. Nevertheless, disputations
      were once aroused for some complications. Aimed to have a better understanding of
      the specific role of T-80 coating on nanoparticles and simplify the problem, the
      direct observation of brain targeting combined with in vivo experiments was
      carried out in this work using the model nanoparticles (MNPs). The presence of a
      complex composed by the model loading, T-80 and nanoparticles was found in the
      preparation of MNPs. The result was further supported by some surface properties
      of MNPs. Being bound to nanoparticles that were overcoated by T-80 later, was
      necessary for the loading to be delivered to brain. Partial coverage was enough
      for T-80 coating to play a specific role in brain targeting. It seemed that brain
      targeting of nanoparticles was concerned with the interaction between T-80
      coating and brain micro-vessel endothelial cells. Therefore, the specific role of
      T-80 coating on nanoparticles in brain targeting was confirmed.

PMID- 14967541
TI  - Coupling of therapeutic molecules onto surface modified coralline hydroxyapatite.
AB  - Surface modification and coupling of therapeutic molecules, tetracycline, onto
      coralline hydroxyapatite (CHA) and their in vitro evaluations were described in
      this study. Initially, CHA was graft polymerized with glycidylmethacrylate (GMA)
      using redox initiators and subsequently coupled to tetracycline through epoxy
      groups. The CHA grafted with polyGMA (CHA-g-PGMA) was characterized by Fourier
      transform infrared spectroscopy and powder X-ray diffraction (XRD) for proof of
      grafting. The absorption peaks pertaining to epoxy and ester carbonyl groups were
      observed for the graft polymer due to PGMA grafting. The XRD results signified
      that there was no secondary phase in the apatite lattice and crystallinity was
      also not affected by grafting, which suggested that the PGMA chains were grafted
      only on the surface of CHA. Drug loading and releasing was evaluated and found
      that CHA-g-PGMA exhibited higher loading efficiency than CHA. The in vitro
      release of tetracycline was performed in phosphate buffered saline under
      physiological condition and the release profiles showed that the tetracycline
      containing graft polymer releases the drug for prolonged period as compared to
      CHA. Based on the experimental results, CHA-g-PGMA appears to be a promising
      biomaterial for drug delivery.

PMID- 14967542
TI  - Heparin coated poly(alkylcyanoacrylate) nanoparticles coupled to hemoglobin: a
      new oxygen carrier.
AB  - A new generation of drug delivery systems based on heparin
      poly(isobutylcyanoacrylate) copolymers has been developed to carry hemoglobin.
      These copolymers spontaneously form, in water, nanoparticles with a ciliated
      surface of heparin. These nanoparticles maintain the heparin antithrombotic
      properties and inhibit complement activation. One ml of nanoparticle suspension
      can be loaded with up to 2.1mg of hemoglobin, which preserves its ligand binding
      capacity. This work constitutes the first demonstration of hemoglobin loaded on
      nanoparticle surface, rather than being encapsulated. With a size of 100 nm,
      these drug delivery systems make suitable tools in the treatment of thrombosis
      oxygen deprived pathologies.

PMID- 14967543
TI  - Thermal expansion characteristics of light-cured dental resins and resin
      composites.
AB  - The thermal expansion characteristics of dental resins prepared by light-curing
      of Bis-GMA, TEGDMA, UDMA, Bis-EMA(4) or PCDMA dimethacrylate monomers and of
      commercial light-cured resin composites (Z-100 MP, Filtek Z-250, Sculpt-It and
      Alert), the organic matrix resin of which is based on different combinations of
      the above monomers, were studied by thermomechanical analysis (TMA). This study
      showed the existence of a glass transition temperature at around 35-47 degrees C
      for the resins and 40-45 degrees C for the composites; then the coefficient of
      linear thermal expansion (CLTE) was calculated at the temperature intervals 0-60
      degrees C, 0-T(g) and T(g)-60 degrees C. The CLTE values of Bis-GMA, TEGDMA and
      UDMA resins are similar and lower than those of Bis-EMA (4) and PCDMA resins. The
      CLTE values of the composites indicated that the major factor that affects the
      CLTE of a composite is the filler content, but it also seems to be affected by
      the chemical structure of the matrix resin. TMA on water-saturated samples showed
      that water desorption takes place during the measurement and that the residual
      water acts as a plasticizer decreasing the T(g) and increasing the CLTE values.
      Furthermore, TMA on post-heated samples for 1, 3 or 6h showed, only for the
      resins, an initial decrease of CLTE and increase of the T(g) after 1h that was
      not significantly changed after 6h of heating.

PMID- 14967544
TI  - Synthesis and characterisation of cationically modified phospholipid polymers.
AB  - Phospholipid-like copolymers based on 2-(methacryloyloxyethyl) phosphorylcholine
      were synthesised using monomer-starved free radical polymerisation methods and
      incorporating cationic charge in the form of the choline methacrylate monomer in
      amounts varying from 0 to 30 wt%, together with a 5 wt% silyl cross-linking agent
      in order to render them water-insoluble once thermally cured. Characterisation
      using a variety of techniques including nuclear magnetic resonance spectroscopy,
      high-pressure liquid chromatography and gel permeation chromatography showed the
      cationic monomer did not interfere with the polymerisation and that the desired
      amount of charge had been incorporated. Gravimetric and differential scanning
      calorimetry methods were used to evaluate the water contents of polymer membranes
      cured at 70 degrees C, which was seen to increase with increasing cation content,
      producing materials with water contents ranging from 50% to 98%. Surface plasmon
      resonance indicated that the coatings swelled rapidly in water, the rate and
      extent of swelling increasing with increasing cation level. Dynamic contact angle
      showed that coatings of all the polymers possessed a hydrophobic surface when dry
      in air, characteristic of the alkyl chains expressed at the surface (>100 degrees
      advancing angle). Rearrangement of the hydrophilic groups to the surface occurred
      once wet, to produce highly wettable surfaces with a decrease in advancing angle
      with increasing cation content. Atomic force microscopy showed all polymer films
      to be smooth with no features in topographical or phase imaging. Mechanical
      properties of the dry films were also unaffected by the increase in cation
      content.

PMID- 14967545
TI  - Protection of polynucleotides against nuclease-mediated hydrolysis by
      complexation with schizophyllan.
AB  - Schizophyllan is a beta-(1-->3)-D-glucan existing as a triple helix in water and
      as a single chain in dimethylsulfoxide (DMSO), respectively. As we already
      reported, when some homo-polynucleotide (for example, poly(dA) or poly(C)) is
      added to the schizophyllan/DMSO solution and subsequently DMSO is exchanged for
      water, the single chain of schizophyllan (s-SPG) forms a complex with the
      polynucleotide. The present work demonstrates that the polynucleotide bound in
      the complex is more stable to nuclease-mediated hydrolysis than the
      polynucleotide itself (i.e., naked polynucleotide), using high-performance liquid
      chromatography and ultraviolet absorbance technique. A kinetic study for the
      hydrolysis clarified that the simple Michaelis-Menten relation is held and the
      maximum velocity for the complex is one-sixth as small as that of the naked
      polynucleotide. This low hydrolysis rate for the complex suggests that s-SPG is
      applicable to a carrier for antisense oligonucleotides.

PMID- 14967546
TI  - Antisense oligonucleotides bound in the polysaccharide complex and the enhanced
      antisense effect due to the low hydrolysis.
AB  - Schizophyllan is a beta-(1-->3)-D-glucan and can form a novel complex with some
      single-chains of DNAs. As the preceding paper revealed, the polynucleotide bound
      in the complex is more stable to nuclease-mediated hydrolysis than the
      polynucleotide itself (i.e., naked polynucleotide). This paper examined
      possibility to apply this complex to an antisense DNA carrier, using an in vitro
      (cell-free) transcription/translation assay. In this assay, we used a plasmid DNA
      coding a green fluorescence protein (GFP) and an antisense DNA designed to
      hybridize the ribosome-binding site in the GFP-coded mRNA. When the antisense DNA
      was administered as the complex, a lower GFP expression efficiency (or higher
      antisense effect) is observed over naked DNA. This is because the antisense DNA
      in the complex is protected from the attack of deoxyribonuclease. When
      exonuclease I, which specifically hydrolyzes single DNA chains, was present in
      the GEP assay system, the antisense effect was not changed for the complex while
      being weakened in the naked antisense DNA system. These results imply that the
      exonuclease I cannot hydrolyze the antisense DNA in the complex, while it can
      hydrolyze naked DNA to reduce its antisense effect.

PMID- 14967547
TI  - Durability of cognitive remediation training in schizophrenia: performance on two
      memory tasks at 6-month and 12-month follow-up.
AB  - Patients with schizophrenia have consistently been found to exhibit cognitive
      deficits, particularly in memory, which have been suggested to mediate functional
      outcomes. Several recent reviews of cognitive retraining have concluded that
      these deficits respond to training, although the sustainability of cognitive
      improvement following completion of training has not been adequately evaluated.
      Most studies had small samples and very short follow-up periods. As part of a
      larger study, we examined performance on two memory tasks in two groups of
      participants: those who received computerized cognitive remediation training in
      addition to work therapy (n=45), vs. those who only received work therapy (n=49).
      Computerized cognitive remediation included hierarchical training on a
      computerized digit span task and a computerized words serial position task.
      Assessments using the same computerized tasks were made at three time points:
      baseline, end of active intervention, and 6-month follow-up. Compared to the
      active control condition (work therapy only), the group receiving computerized
      cognitive remediation in addition to work therapy showed significantly greater
      improvements on the trained digit span task following training. These
      improvements were maintained at the 6-month follow-up. There were no significant
      group differences on the word serial position task at any time point. Results
      indicate that computerized training can lead to sustained improvements on some,
      but not all, training tasks.

PMID- 14967548
TI  - Recognition of metaphor and irony in young adults: the impact of schizotypal
      personality traits.
AB  - Patients with schizophrenia demonstrate two dissociable impairments of pragmatic
      language comprehension: (1) an insensitivity to irony, which is associated with
      poor theory-of-mind (i.e. a difficulty with inferring other people's thoughts);
      and (2) poor recognition of metaphors, which may reflect degraded semantics. This
      study investigated whether non-clinical high-schizotypal adults show similar
      impairments of pragmatic language. Thirty-six university students completed the
      Raine Schizotypal Personality Questionnaire, the Wechsler Memory Scale Logical
      Memories subtest, Raven's Progressive Matrices and a story comprehension task
      that tested the ability to discriminate between incongruous statements and
      appropriate uses of ironical, metaphorical or literal speech. Counter to the
      pattern found for patients, high-schizotypal adults were just as capable as low
      schizotypal adults of identifying appropriate metaphors, suggesting a
      discontinuity between schizophrenia and schizotypy for the metaphor-recognition
      problem. This study's finding of intact metaphor recognition in high-schizotypal
      adults contrasts with previous findings of poor proverb comprehension in these
      individuals and is interpreted in terms of different semantic processes required
      for recognizing and interpreting metaphors. Consistent with the pattern found for
      patients, high-schizotypal adults were significantly impaired in their ability to
      appreciate when a literally contradictory utterance could be interpreted as
      ironical, suggesting continuity between schizophrenia and schizotypy for the
      irony-appreciation problem.

PMID- 14967549
TI  - Minor physical anomalies in patients with schizophrenia and their parents:
      prevalence and pattern of craniofacial abnormalities.
AB  - The frequency of minor physical anomalies (MPAs) in patients with schizophrenia
      suggests an early disturbance in the development of the neuroectoderm. To improve
      the phenotypic delimitation of this disorder, we used a comprehensive scale of
      MPAs (41 items) in patients with schizophrenia and their first-degree relatives.
      This scale, adapted from a revised version of the Waldrop Scale (Ismail et al.
      Minor physical anomalies in schizophrenic patients and their siblings, American
      Journal of Psychiatry 155, 1998a, 1695-1702), introduced new items assessing
      facial and limbs asymmetry. The interrater reliability between two examiners was
      good: intraclass correlation coefficient: 0.68 (0.42-0.92). Patients with
      schizophrenia (n=40; mean=5.8, S.D.=4) and their non-psychotic parents (n=45;
      mean=4.7, S.D.=2.8) had significantly more MPAs than healthy comparison subjects
      (n=42; mean=2.2, S.D.=1.2). A logistical regression model showed the ability of
      several items to predict group status, including facial asymmetry, cleft palate,
      hair whorls and abnormal palmar crease. The high prevalence of facial asymmetry
      in patients with schizophrenia and their first-degree relatives provides new
      insights into the underlying dysembryogenic processes. This revised scale thus
      appears to be a useful complementary tool in pathophysiological studies aiming at
      the identification of developmental factors in schizophrenia.

PMID- 14967550
TI  - Effects of hyperventilation on heart rate and QT variability in panic disorder
      pre- and post-treatment.
AB  - Panic disorder is associated with an elevated risk of cardiovascular disease and
      sudden death. Individuals with panic disorder have been shown to have reduced
      variability in heart rate and increased variability in the QT interval on
      electrocardiogram (ECG), patterns predictive of sudden cardiac death in certain
      forms of cardiomyopathy. Given that panic disorder patients often hyperventilate
      during a panic attack, we assessed the effects of voluntary hyperventilation on
      the ECG utilizing linear analyses of heart rate and QT interval variability.
      Sixteen symptomatic, medication-free patients underwent hyperventilation
      challenge. A small subgroup of eight subjects underwent re-challenge after
      treatment. Pre-treatment, hyperventilation resulted in a decrease in a measure of
      heart rate variability and an increase in the QT variability index (QTVI; QT
      variance normalized for mean QT, divided by heart rate variance normalized for
      mean heart rate). In a remitted state, the QTVI was reduced both during rest and
      during hyperventilation compared with the respective pre-treatment levels. These
      findings suggest a possible mechanism explaining increased rates of
      cardiovascular morbidity and mortality in panic disorder. Moreover, the reduction
      in QTVI observed post-treatment raises the question of whether treatment might
      have cardioprotective effects, at least in panic disorder patients who have
      particular types of co-morbid cardiac disease. Yet these results must be
      interpreted cautiously; they are preliminary, exploratory and observed in a very
      small sample without a healthy comparison group.

PMID- 14967551
TI  - Treatment of panic disorder with agoraphobia in an anxiety disorders clinic:
      factors influencing psychiatrists' treatment choices.
AB  - The main objective of this report was to identify patient characteristics that
      led psychiatrists in an academic anxiety disorders clinic to make a decision
      about intensive treatment of patients with panic disorder with agoraphobia (PDA)
      with cognitive-behavioral therapy (CBT) alone, CBT plus a high-potency
      benzodiazepine (CBT+BZ) or CBT combined with BZ and an antidepressant, fluoxetine
      (CBT+BZ+AD). On the basis of their clinical judgment and collaborative
      negotiation with the patient, psychiatrists chose one of the three treatment
      modalities for 102 PDA outpatients. Two stepwise logistic regressions were
      performed to explore pre-treatment patient characteristics the psychiatrists may
      have considered in choosing among these treatments. One regression examined the
      decision to add BZ to CBT, while the other examined the decision to add AD to
      CBT+BZ. Psychiatrists generally used combination treatments in patients with more
      severe PDA. CBT alone was a more likely choice for dominant anxiety-related
      cognitive phenomena. Patients with prominent panic attacks and somatic symptoms
      were more likely to be treated with CBT+BZ, while those who also had significant
      depressive symptoms and higher disability levels were more likely to receive
      CBT+BZ+AD. Patients in all three treatment groups showed significant reduction in
      symptoms during intensive treatment and reached similar end states. In a clinic
      setting where CBT is accepted as the basic treatment for PDA, psychiatrists added
      BZ to control prominent panic symptoms and added AD to elevate depressed mood and
      help cope with marked disability. These choices appear rational and resulted in
      substantial clinical improvement at the end of intensive treatment in the clinic.

PMID- 14967552
TI  - Overvalued ideation as a predictor of fluvoxamine response in patients with
      obsessive-compulsive disorder.
AB  - The presence of overvalued ideation (OVI) in patients with obsessive-compulsive
      disorder (OCD) has been theoretically linked to poorer treatment outcome. OVI has
      recently been shown to predict treatment outcome in OCD. The purpose of the
      present study is to determine whether OVI predicts medication treatment response,
      controlling for initial symptom severity and measurement error. The sample
      consisted of 34 outpatients diagnosed with OCD who completed an open-label
      clinical trial of fluvoxamine of 10 weeks' duration. Clinicians administered the
      Overvalued Ideas Scale (OVIS) at baseline. Symptom severity was rated at baseline
      and at the end of week 10 using the Yale-Brown Obsessive-Compulsive Scale. Of
      those who completed the trial, 68% showed a reliable change in obsessions and 62%
      showed a reliable change in compulsions. Analysis of variance showed that
      baseline OVIS predicted outcome for obsessions, but not compulsions. A key
      limitation was the relatively low number of individuals in the upper quartile on
      the OVIS, thus reducing the predictive power of the measure in relation to
      treatment outcome. Future research should examine medication treatment outcome
      with higher scoring patients.

PMID- 14967553
TI  - Investigating the use of contingency management in the treatment of cocaine abuse
      among individuals with schizophrenia: a feasibility study.
AB  - This small-scale study was conducted to examine the feasibility of using voucher
      based reinforcement therapy (VBRT) as a treatment modality for cocaine abuse
      among individuals with schizophrenia. Cocaine use was reduced in three
      individuals with a diagnosis of schizophrenia during a VBRT intervention.
      Interestingly, all of the abstinence occurred during the first half of the
      intervention. This early period of sobriety may represent a clinically relevant
      window of opportunity during which intensive psychosocial or social work
      interventions might have a greater chance for success.

PMID- 14967554
TI  - Tumor necrosis factor alpha gene-G308A polymorphism associated with bipolar I
      disorder in the Korean population.
AB  - We conducted a case-control association study between the -G308A tumor necrosis
      factor (TNF)-alpha gene polymorphism and 89 patients with bipolar I disorder
      (BID). A polymerase chain reaction method was used. We found significant
      differences in genotype and allele distribution. The -G308A TNF-alpha gene
      polymorphism may confer a risk for BID in the Korean population.

PMID- 14967555
TI  - Recontamination as a source of pathogens in processed foods.
AB  - Food products that have been submitted to an adequate heat-treatment during
      processing are free of vegetative pathogens and, depending on the treatments, of
      sporeformers and are generally regarded as safe. Processed products such as pate,
      ice cream, infant formulae and others have nevertheless been responsible for food
      borne illnesses. Thorough epidemiological investigations of several of these
      outbreaks have demonstrated that the presence of vegetative pathogens such as
      Salmonella spp. or Listeria monocytogenes in the consumed products was frequently
      due to post-process recontamination. The majority of studies on pathogens in
      foods are devoted to investigations on their presence in raw materials or on
      their growth and behaviour in the finished products. Reference to recontamination
      is, however, only made in relatively few publications and very little is
      published on the sources and routes of these pathogens into products after the
      final lethal processing step. The investigation of an outbreak, including
      epidemiological studies and typing of strains, is very useful to trace the origin
      and source of the hazard. Published data demonstrate that the presence of
      pathogens in the vicinity of unprotected product in processing lines represents a
      significant risk of recontamination. Microbiological Risk Assessment studies can
      be conducted as part of governmental activities determining appropriate
      protection levels for populations. Although recontamination has been identified
      as a relevant cause of food incidences, it is often not considered in such
      studies. This paper advocates that an effort should be made to develop our
      knowledge and information on recontamination further and start using it
      systematically in the exposure assessment part of Microbiological Risk Assessment
      studies.

PMID- 14967556
TI  - Effects of chlorine and pH on efficacy of electrolyzed water for inactivating
      Escherichia coli O157:H7 and Listeria monocytogenes.
AB  - The effects of chlorine and pH on the bactericidal activity of electrolyzed (EO)
      water were examined against Escherichia coli O157:H7 and Listeria monocytogenes.
      The residual chlorine concentration of EO water ranged from 0.1 to 5.0 mg/l, and
      the pH effect was examined at pH 3.0, 5.0, and 7.0. The bactericidal activity of
      EO water increased with residual chlorine concentration for both pathogens, and
      complete inactivation was achieved at residual chlorine levels equal to or higher
      than 1.0 mg/l. The results showed that both pathogens are very sensitive to
      chlorine, and residual chlorine level of EO water should be maintained at 1.0
      mg/l or higher for practical applications. For each residual chlorine level,
      bactericidal activity of EO water increased with decreasing pH for both
      pathogens. However, with sufficient residual chlorine (greater than 2 mg/l), EO
      water can be applied in a pH range between 2.6 (original pH of EO water) and 7.0
      while still achieving complete inactivation of E. coli O157:H7 and L.
      monocytogenes.

PMID- 14967557
TI  - Identification of lactic acid bacteria isolated from South African brandy base
      wines.
AB  - In brandy base wines, no sulphur dioxide is used and it therefore is ideal for
      the proliferation of lactic acid bacteria. As part of an extensive taxonomic
      survey within the ecological framework of South African vineyards and wineries,
      and the influence of naturally occurring lactic acid bacteria on the quality of
      wine and brandy, a total of 54 strains were isolated from grape juice and at
      different stages of brandy base wine production. The strains were identified
      using numerical analysis of total soluble cell protein patterns, 16S rRNA
      sequence analyses and polymerase chain reaction (PCR) using species-specific
      primers. The predominant species was Oenococcus oeni (22 strains), but
      Lactobacillus brevis (8 strains), Lactobacillus paracasei (8 strains) and
      Lactobacillus plantarum (6 strains) were also isolated frequently. Many of the O.
      oeni strains were isolated from brandy base wines after completion of spontaneous
      malolactic fermentation (MLF). The Lactobacillus spp. were isolated from all the
      different stages of brandy base wine production. Lb. plantarum was the dominant
      species in the juice, but disappeared during the later stages of production.
      However, Lactobacillus hilgardii, Lb. brevis and Lb. paracasei were also isolated
      from base wine after spontaneous MLF. Strains identified as Lactobacillus
      vermiforme were isolated during the alcoholic fermentation and after MLF have
      been completed. Total soluble cell protein patterns grouped O. oeni strains into
      two phenotypic groups. Two phenotypic clusters have also been identified for the
      Lb. brevis isolates. The Lb. paracasei isolates all grouped in one cluster. This
      is the first report of the presence of Lb. paracasei and Lb. vermiforme in brandy
      base wines. The presence of the Lactobacillus spp. could be correlated to the
      decrease in quality of the base wine and distillate, while O. oeni strains were
      found to have a more favourable influence on the quality of base wine and
      distillates. These results shed some light on the ecology and oenological
      influence of lactic acid bacteria (LAB) on the quality of South African brandy.

PMID- 14967558
TI  - Isolation and characterisation of Arcobacter butzleri from meat.
AB  - A survey was conducted to determine the prevalence of Arcobacter in ground
      chicken, pork, beef and lamb meats. Meat samples were enriched in Arcobacter
      broth (AB) containing cefoperazone, amphotericin and teicoplanin (CAT)
      supplement. Samples were screened for the presence of Arcobacter spp. using a
      multiplex polymerase chain reaction (PCR) followed by isolation on blood and
      selective agar. Arcobacter butzleri was the only species of Arcobacter isolated
      from 35% of 88 samples of ground meats. A. butzleri was more frequently isolated
      from poultry (73%) than pork (29%), beef (22%) or lamb (15%) samples. No
      significant differences were found in the isolation rates and from the different
      regions sampled. Isolates were characterised by pulsed-field gel electrophoresis
      (PFGE) using SacII, EagI and SmaI restriction endonucleases. A number of isolates
      with indistinguishable PFGE fingerprints were found to be epidemiologically
      related, which may indicate cross-contamination of common types of Arcobacter
      from different meat species or between meat species. The public health
      significance of Arcobacter in ground meat needs to be determined.

PMID- 14967559
TI  - Effects of peroxyacetic acid, acidified sodium chlorite or lactic acid solutions
      on the microflora of chilled beef carcasses.
AB  - The effects of solutions of 0.02% peroxyacetic acid, acidified 0.16% sodium
      chlorite, 2% lactic acid and 4% lactic acid on the natural flora of the distal
      surfaces of pieces of brisket, from chilled beef carcass quarters delivered from
      two slaughtering plants to a processing plant, were investigated. Peroxyacetic
      acid and acidified sodium chlorite solutions had little effect on the numbers of
      aerobes, coliforms or Escherichia coli on meat from one plant, and were less
      effective than 4% lactic acid for reducing the numbers of bacteria on meat from
      the other plant. With meat from both plants, treatment of meat with 4% lactic
      acid and holding for 5 or 60 min at 7+/-1 degrees C before sampling resulted in
      reductions of all three groups of bacteria by >/=1.5 log unit. Treatment with 2%
      lactic acid resulted in similar reductions when meat was sampled 5 min after the
      treatment, but reductions were about 1 log unit when meat was sampled 60 min
      after the treatment. Treatment of carcass quarters with 4% lactic acid resulted
      in reductions of bacterial numbers of >/=2 log units at distal surfaces, but </=2
      log units at medial surfaces. The findings indicate that the efficacies of
      antimicrobial solutions may be inconsistent when they are applied to chilled meat
      from different sources and to different types of meat surface, and that bacteria
      injured by application of an antimicrobial solution may recover during processing
      of meat at temperatures about 7 degrees C. However, 4% lactic acid may be
      generally useful as a decontaminant for chilled, raw meat.

PMID- 14967560
TI  - Genetic diversity and virulence gene determinants of antibiotic-resistant
      Salmonella isolated from preharvest turkey production sources.
AB  - This study evaluated the molecular diversity of 29 Salmonella serotypes isolated
      from turkey ceca and the production environment. Isolates were resistant to
      bacitracin (100%), erythromycin (100%), novobiocin (100%), rifampin (100%),
      streptomycin (62%), gentamicin (52%), spectinomycin (48%), tetracycline (31%),
      sulfamethoxazole/trimethoprim (SXT) (3%) and tobramycin (3%). The minimum
      inhibitory concentration (MIC) values ranged from 32 to >/=1024 microg/ml. The
      pulsed-field gel electrophoresis (PFGE) and ribotyping patterns were identical
      within each of the serotypes Heidelberg, Worthington and Muenster. The plasmid
      profiles were identical within each of the Salmonella serotypes. Two different
      clones of Salmonella anatum were differentiated by PFGE typing but not by
      ribotyping. Heidelberg isolates from nine turkey ceca and three drinker samples
      had identical antibiotic resistance, PFGE, ribotype and plasmid patterns,
      suggesting that transmission of this particular clone may have occurred between
      the birds and the drinkers. Identical PFGE, ribotype and plasmid patterns were
      observed in one Salmonella worthington isolate from turkey ceca in one flock and
      two S. worthington isolates from feeder contents and drinkers from a subsequent
      flock, suggesting transmission of this pathogen between flocks. Individual and
      multiple polymerase chain reaction (PCR) analyses revealed the presence of the
      virulence genes invA, aceK and sopB and the absence of the h-1i gene in all
      isolates. A combination of genotypic and phenotypic markers can be useful in
      studying genetic variation among natural salmonellae populations in turkey
      production and delineating possible transmission pathways.

PMID- 14967561
TI  - Influence of the sigB gene on the cold stress survival and subsequent recovery of
      two Listeria monocytogenes serotypes.
AB  - The influence of serotype and the role of the sigB gene of Listeria monocytogenes
      during the survival and recovery on different substrates were determined. Wild
      type and sigB mutants of two serotypes of L. monocytogenes were inoculated into
      buffer and onto beef steaks, and incubated at 4 degrees C for 8 weeks during
      which samples were removed and Listeria numbers determined. Growth kinetics of
      stationary phase wild-type and sigB mutant cells were compared, without
      prechilling and after prechilling at 4 degrees C. The two serotypes had similar
      survival capabilities under the conditions examined, and the sigB gene was
      influential in survival of chill stress, but was dependent upon additional
      nutritional factors. Prechilling cells prior to growth extended the lag phase of
      both strains, and this lag phase extension was compounded by the absence of a
      functional sigB gene. In conclusion, the sigB gene is involved in the survival
      and recovery from chill stress by the two serotypes tested. Additional factors
      such as previous growth conditions, nutritional requirements and serotype
      susceptibility are also contributory. This study adds relevant information
      regarding the influence of the sigB gene, in conjunction with the historical
      growth conditions and serotype differences. Understanding the significance of
      these factors may be useful in creating improved recovery systems for the
      detection of L. monocytogenes from at-risk foods.

PMID- 14967562
TI  - Inhibition of foodborne bacteria by the lactoperoxidase system in a beef cube
      system.
AB  - Biopreservatives are being developed to inhibit the growth of foodborne pathogens
      and thus improve food safety. The lactoperoxidase system (LPS) is a naturally
      occurring system that has potential for use as an antimicrobial agent in foods.
      Growth of single strains of the pathogens Staphylococcus aureus, Listeria
      monocytogenes, Escherichia coli O157:H7, Salmonella enterica subsp. enterica
      serovar Typhimurium, Yersinia enterocolitica, Pseudomonas aeruginosa and beef
      microflora were assessed on LPS-treated meat surfaces in an experimental system.
      Beef cubes inoculated with approximately 10(4) cfu cm(-2) of bacteria were
      treated with the LPS and incubated at 37 degrees C for 24 h, 12 degrees C for 7
      days or in a chilling regime: 12 to -1 degrees C over 1 week and held at -1
      degrees C for 4 weeks. Treatment with LPS was more effective at storage
      temperatures non-permissive for rapid bacterial growth with strong inhibition of
      growth achieved on LPS-treated cubes at 12 degrees C and reduction in pathogen
      viable counts at chilling temperatures. At chilling temperatures, the LPS
      inhibited the growth of native pseudomonads but did not prevent the development
      of native lactic acid bacteria.

PMID- 14967563
TI  - On the origin of the deviation from the first-order kinetics in inactivation of
      microbial cells by pulsed electric fields.
AB  - A computer model was developed for the estimation of the kinetics of microbial
      inactivation by pulsed electric field (PEF). The model is based on the
      electroporation theory of individual membrane damage, where spherical cell
      geometry and distribution of cell sizes are assumed. The variation of microbial
      cell sizes was assumed to follow a statistical probability distribution of the
      Gaussian type. Surviving kinetics was approximated by Weibull equation. The
      dependencies of two Weibull parameters (shape n and time tau, respectively)
      versus electric field intensity E and width of cell diameters distribution were
      studied.

PMID- 14967564
TI  - Viability loss and morphology change of foodborne pathogens following exposure to
      hydrostatic pressures in the presence and absence of bacteriocins.
AB  - Cell suspensions of three pathogens were exposed to hydrostatic pressure (HP),
      bacteriocin mixture (nisin and pediocin) or a combination of HP+bacteriocins and
      changes in colony forming units (cfu) and cell-morphology by scanning electron
      microscopy (SEM) were studied. Cell viability loss, as determined from the
      reduction in cfu before and after a treatment, occurred in Listeria monocytogenes
      by all three treatments and in Salmonella typhimurium and Escherichia coli
      O157:H7 by HP and HP+bacteriocin combination. Cell wall and cell membrane
      collapse and cell lysis was indicated in L. monocytogenes exposed to bacteriocin
      or HP+bacteriocin and in Salmonella and E. coli exposed to HP or HP+bacteriocin.

PMID- 14967565
TI  - Ice as a vehicle for diarrheagenic Escherichia coli.
AB  - In a recent study of the microbiological quality of commercial ice, 50
      Escherichia coli isolates belonging to different serotypes were found. The
      potential hazard from these isolates was examined by testing their adherence
      patterns in HeLa cells and searching for the presence of DNA sequences related to
      E. coli virulence properties. Twelve potentially diarrheagenic isolates were
      found and classified as enteroaggregative E. coli (EAEC) based on their ability
      to produce aggregative adherence to HeLa cells. The remaining isolates were
      devoid of the virulence properties searched for. The EAEC isolates belonged to 10
      different serotypes, among which O128ab:H35 is often found in diarrheic feces.
      None of these isolates reacted with a specific EAEC DNA probe or carried any of
      the known EAEC virulence genes. These data indicate that ice may be an important
      vehicle for transmission of enteropathogens, especially of the EAEC group.

PMID- 14967566
TI  - [Interest of the criteria of Cochin to select patients with significant relief of
      low back pain after corticosteroid facet joint injections: a prospective study].
AB  - The seven Criteria of Cochin (CC), clinical descriptive criteria of low back pain
      (LBP), have been shown to be able to select patients whose LBP would respond well
      to facet joint anesthesia. AIM: To determine if these seven criteria set are able
      to select patients with significant relief of LBP after corticosteroid facet
      joint injections (CFJI). METHODS: Ninety-one patients with chronic LBP were
      included in a positive group (PG) or a negative group (NG) according to the
      number of the positive CC. Patients placed in the PG had five or more of the
      positive CC and those in the NG had less than five of the positive CC. All of
      them received CFJI on day 0 (D0). The severity of LBP and leg pain, disability
      and CFJI effect were evaluated on a self-questionnaire on D0, D2, D8 and D30.
      RESULTS: Two hundred and seventeen CFJI were performed (mean 2.1 per patient).
      Compared to the initial values we observed a significant reduction of the LBP at
      D2, D8 and D30 in both the groups (P < 0.05), a significant augmentation of the
      leg pain at D30 in the GN (P < 0.05) and a significant improvement of the Quebec
      back pain disability scale (QBDS) at D8 and D30 in the PG (P <0.05). Compared to
      the NG values, the PG had a significant higher global estimation of the efficacy
      of the treatment (P < 0.05) and a significant lesser intensive LBP (P <0.05) on
      D2, D8 and D30, a significant lesser intensive leg pain (P < 0.05) on D30, and a
      tendency to a more important reduction of the QBDS on D8 and D30 (P > 0.05).
      CONCLUSION: CC seems to be an effective test to select patients whose LBP would
      respond well to CFJI.

PMID- 14967567
TI  - [A long-term follow up of the shoulder in obstetrical brachial palsy].
AB  - OBJECTIVES: To study shoulder impairment and disability caused by obstetrical
      brachial plexus palsy, their evolution under physical and surgical treatments,
      and the place of complementary explorations in persistent sequels. METHODS: From
      1991 to 2000, 129 patients (66 M, 63 F) were included in a retrospective study.
      Impairment was assessed by muscle recovery (deltoid, biceps, external rotators)
      and shoulder passive motion. Disability was assessed by Mallet functional test.
      RESULTS: Full spontaneous recovery was noted in 20% of patients before the age of
      3 months. Repair of the nerve lesion was undertaken in four children between the
      18th and 24th months. Full recovery of deltoid and biceps was noted in three
      fourth of whole cases before the 12th month, and of the external rotation in only
      45% at this same age. Seventy-seven percent of patients showed stage >or= III of
      Mallet test (VI: 20%, IV: 32%; III: 25%) at a middle age of 3.5 years. A long
      term follow-up showed an external rotation limited less than 20 degrees in 15
      children. Investigation by RMN or Arthroscanner was realized for five patients,
      this reveals a deformation with subluxation of the humeral head in two cases. Ten
      children were operated (liberation of sub-scapula in nine cases associated to a
      tendinous transfer six times; humeral osteotomie in one case). This surgery has
      allowed the improvement of the functional state in all cases. CONCLUSION: After
      effects in shoulder are frequent especially the limitation of external rotation,
      which can lead to a deformation, and subluxation of the humeral head. The authors
      insist on the importance to push investigations in case of limitation of the
      passive external rotation to improve the therapeutic choice.

PMID- 14967568
TI  - [Palatal myoclonus and dysphagia].
AB  - INTRODUCTION: Post brainstem lesion dysphagia is frequently associated with
      palatal myoclonus (PM) but the correlation between these two symptoms is still
      unclear. OBJECTIVE: The aim of this study was to verify the relationship between
      PM and dysphagia, and if PM could itself induce dysphagia. PATIENTS AND METHODS:
      Twelve patients suffering from post brainstem lesion PM and dysphagia; 10 male
      and two female, mean aged of 50.5 years, were assessed using clinical
      examination, radiological and endoscopic examination of deglutition. RESULTS: In
      three cases, PM were associated with pharyngeal area decreasing, laryngeal
      aspiration, and dysphagia. DISCUSSION: This study confirms the hypothesis of
      close relationship between PM and dysphagia. In these cases, specific dysphagia
      therapy should be recommended. CONCLUSION: Post brainstem lesion dysphagia is
      sometimes associated with PM and in some cases, there is probably a relationship
      between PM and swallowing disorders of these patients.

PMID- 14967569
TI  - [Use of isokinetic techniques vs standard physiotherapy in patients with chronic
      low back pain. Preliminary results].
AB  - OBJECTIVE: To determine if the use of an isokinetic device for trunk exercise is
      more effective than standard physiotherapy in promoting motor disinhibition for
      patients with chronic low back pain. POPULATION: chronic low back pain
      outpatients who are treated in a Rheumatology or PM & R unit within an academic
      hospital. METHODOLOGY: This is a prospective, controlled, randomized study, with
      two groups of treatment: one treated with isokinetic techniques and the other
      with standard physiotherapy, six sessions for each treatment during 2 weeks.
      Outcome measures include pain (VSA), trunk mobility (Schober index, distance from
      fingers to floor), muscle extensibility and muscle strength (Biering-Sorensen and
      Shirado-Ito test), and functional capacity (Quebec scale). RESULTS: Seventeen
      subjects were enrolled. The results suggest that both isokinetic exercise and
      physiotherapy result in improved range of motion, extensibility, muscle strength,
      and pain, without any significant superiority of one technique over the other.
      However, each technique has specific advantage. DISCUSSION: Despite methodologic
      limitations, this study shows that isokinetic exercise is not better than
      physiotherapy in reversing motor inhibition in chronic low back pain. Our results
      are consistent with those of other studies in the literature, with regard to the
      absence of established overall superiority of one exercise technique or program
      over the other in this population, and with regard to partial benefits of
      specific exercise techniques. CONCLUSION: The non-specific benefit of one
      technique indicates that further studies are needed to evaluate the benefit of
      combining exercise techniques in chronic low back pain, in order to address the
      multiple factors involved in this pathology.

PMID- 14967570
TI  - [Critical review of the evaluation of the results of upper limb functional
      surgery in tetraplegia since 50 years].
AB  - OBJECTIVE: To study the methods of assessment of upper limb functional surgery in
      the literature. METHODS: The literature review relating to the years 1950-2002
      was carried out with three data bases: Medline, Pascal, Embase. This review also
      involved a thorough study of non-indexed references. RESULTS: Although many
      instruments or tests are used to assess outcome after surgery, their reliability,
      validity and responsiveness have not been adequately proven. Methodology appears
      to be the major failing of the various scales used to assess these patients. The
      conceptual models underlying the evaluation are all too often unspecified. There
      is a lack of pertinence of the selected tasks for tetraplegics. There is limited
      documentation of the guiding framework or conceptualisation. Furthermore, the
      process of item selection is often unknown. Scales or instruments are also deemed
      to be too insensitive to document the small but meaningful functional gains made
      by tetraplegics after functional surgery. CONCLUSION: To answer the need for a
      specific assessment tool for tetraplegics who undergo functional surgery, we have
      developed a national, multicenter, prospective and longitudinal study based on
      two concepts: the first concept is related to Life Habits that are the activities
      of daily living and social roles recognised by the socio-cultural context of a
      person according to age, sex and social and personal identity. They include
      activities that should be accomplished on a daily basis (nutrition, fitness,
      personal care, communication, mobility, etc.). Life Habits presenting a
      significant level of disruption can create handicap situations. The second
      concept is in relation with Motor Capacities that correspond to the abilities of
      a patient to perform basic and functional tasks regardless of contextual factors
      (environmental and personal factors).

PMID- 14967571
TI  - Multi-planar bending properties of lumbar intervertebral joints following cyclic
      bending.
AB  - OBJECTIVE: To assess the changes in the multi-planar bending properties of
      intervertebral joints following cyclic bending along different directions.
      DESIGN: An in vitro biomechanical study using porcine lumbar motion segments.
      BACKGROUND: Repeated bending has been suggested as part of the etiology of
      gradual prolapse of the intervertebral disc, but the multi-planar changes in
      bending properties following cyclic loading have not been examined in detail.
      METHODS: Porcine lumbar motion segments were subject to 1500 cycles of bending
      along directions of 0 degrees (flexion), 30 degrees, 60 degrees, or 90 degrees
      (right lateral bending). The multi-planar bending moments and hysteresis energies
      were recorded before loading and after various cycle numbers. RESULTS: Repeated
      bending at 30 degrees and 60 degrees resulted in greater decreases in mean
      bending moment and hysteresis energy than bending at 0 degrees or 90 degrees. No
      significant differences were seen between loading groups for the change in
      bending moment along the anterior testing directions, but significant differences
      were observed in the posterior and lateral testing directions, with bending at 30
      degrees causing a significantly greater decrease in bending moment in the postero
      lateral directions. CONCLUSIONS: The change in mechanical properties of porcine
      intervertebral joints due to cyclic bending depend on the direction of loading
      and the direction in which the properties are measured. Loading at 30 degrees
      provokes the most marked changes in bending moment and hysteresis energy.

PMID- 14967572
TI  - Multi-axis passive and active stiffnesses of the glenohumeral joint.
AB  - OBJECTIVE: To investigate passive and active glenohumeral stiffness in the
      anterior, posterior, superior, and inferior directions at different lateral
      positions of the humerus. DESIGN: Glenohumeral stiffness along multiple axes was
      determined in fresh-frozen shoulder specimens under both passive (no simulated
      muscle contraction) and active (with simulated muscle contraction) conditions.
      BACKGROUND: Glenohumeral laxity has been evaluated in various studies with focus
      on one of the multiple directions. However, glenohumeral stiffness characterizing
      the force-displacement relationship and stability has not been evaluated in all
      four directions under passive and active conditions. METHODS: The humeral head
      was translated in the posterior, anterior, inferior and superior directions
      relative to the glenoid with different lateral positions, and multi-axis
      glenohumeral stiffness generated by passive and active structures were
      investigated. RESULTS: Without muscle loading, glenohumeral stiffness in the
      superior direction ( Ksup = 5.83 N/mm) was higher than that in the inferior (
      Kinf = 4.32 ), anterior ( Kant = 3.67 ), and posterior ( Kpost = 2.89 )
      directions ( P < 0.008 ), and Kinf was higher than Kpost ( P = 0.011 ). Stiffness
      in the different directions were correlated to each other ( P < 0.001 ), and
      shifting the humerus laterally increased stiffness in all directions ( P < 0.05 )
      except for the superior direction. With moderate muscle loads, the glenohumeral
      joint became significantly stiffer in all four directions ( P < 0.05 ) with less
      difference among different directions. CONCLUSIONS: Glenohumeral stiffnesses are
      different in the different directions but are correlated to each other and
      contribute jointly to glenohumeral stability. Muscle contractions can increase
      glenohumeral stiffness significantly.

PMID- 14967573
TI  - Effectiveness of tendon transfers for massive rotator cuff tears: a simulation
      study.
AB  - OBJECTIVE To determine what the most effective tendon transfer is in the case of
      a dysfunctional rotator cuff. DESIGN: A tendon transfer procedure of latissimus
      dorsi, teres major or a combination of these two to the insertions of either
      teres minor, infraspinatus, supraspinatus, or subscapularis is simulated using a
      biomechanical musculoskeletal model of the upper extremity. BACKGROUND: Massive
      rotator cuff tears are not easily repaired. To compensate for this loss of
      rotator cuff function other techniques like muscle transfers are developed.
      METHODS: Three range of motion tasks and six activities of daily living of 24
      subjects were measured. Kinematics from these tasks were used as input to the
      Delft Shoulder and Elbow Model. The muscle parameters of the Delft Shoulder and
      Elbow Model were modified to simulate a rotator cuff tear and the ability to
      perform the measured tasks with and without simulated transfer procedures was
      checked. RESULTS: The highest improvements (28-30%, P = 0.00 ) in the ability to
      perform tasks were observed after a simulated tendon transfer of either both
      muscles or teres major alone attached to the supraspinatus or infraspinatus
      insertion. Although all transfer procedures produce significant improvements (P =
      0.00 ), there is a significant difference between the procedures (Chi
      square=58.8, P = 0.00 ) dependent on attachment site. CONCLUSIONS: According to
      the simulation procedure used in the current study, a tendon transfer of teres
      major and latissimus dorsi or teres major alone to the supraspinatus insertion
      appears to be the most effective procedure in the case of a dysfunctional rotator
      cuff. Practical factors, like subacromial space, volume of the muscles and
      tendons, tensile properties and the ability to split the muscles, will finally
      determine which is the preferred transfer option.

PMID- 14967574
TI  - Primary stability of a robodoc implanted anatomical stem versus manual
      implantation.
AB  - OBJECTIVE: To assess the initial stability of anatomical stems implanted in
      manually broached femoral cavities compared with that assessed in cavities milled
      with the robodoc system. DESIGN: The bone-prosthesis interface motion was
      measured in matched pairs of cadaveric femora to assess the initial stability of
      anatomical stems implanted with two different implantation techniques.
      BACKGROUND: The high costs of surgical robots and the increased perioperative
      efforts associated with their use can only be justified if measurable benefits
      for patients can be achieved. Increased initial stability of the stem as an early
      indicator for better bone ongrowth would be such a benefit. METHODS: Seven pairs
      of fresh frozen human cadaveric femora were used. One femur of each pair was
      randomly assigned to receive the robotic milling method; the other femur
      underwent manual broaching by an experienced surgeon. Initial micromotions of the
      anatomical stems were measured during simulated gait cycles with loads of < or
      =1500 N, and both groups underwent matched-pair analysis. Results. High motion of
      the prostheses was found for both implantation techniques. CONCLUSIONS: The
      robodoc system did not enhance the primary stability of the anatomical prosthesis
      compared with the manual broaching method.

PMID- 14967575
TI  - Anterior cruciate ligament rupture translates the axes of motion within the knee.
AB  - OBJECTIVE: To quantify the dynamic effects of anterior cruciate ligament
      deficiency on human knee joint motion. DESIGN: Three-dimensional motion was
      assessed by measuring the kinematics of intact and anterior cruciate ligament
      deficient knee joint specimens during simulated flexion-extension cycles.
      BACKGROUND: It is known that the anterior cruciate ligament plays an important
      role in controlling three-dimensional knee joint motion. Nevertheless, dynamic
      effects of deficiency are not fully understood. METHODS: Six cadaveric knees were
      tested in a knee joint motion and loading apparatus prior to and after anterior
      cruciate ligament resection. To determine if the kinematic results depended on
      additional loading, internal and external rotation moments of 3.4 Nm were axially
      applied to the tibia. The kinematics were analysed in terms of finite helical
      axes. RESULTS: Sectioning the anterior cruciate ligament had little effect on the
      orientations of the finite helical axes. However, applying moments did affect the
      axes orientation. In contrast, relative translations of the axes were
      significantly affected by the deficiency for all rotational moments applied.
      Referring to the individual knee anatomy the largest translation of 12.5 mm
      (median) occurred in medial/lateral direction. CONCLUSIONS: Anterior cruciate
      ligament rupture primarily causes a translation of the finite helical axes in
      medial/lateral direction. Consequently, increased anterior excursion of the tibia
      occurs (subluxation) and therefore dynamic instability.

PMID- 14967576
TI  - Bilateral accommodations to anterior cruciate ligament deficiency and surgery.
AB  - OBJECTIVE To determine bilateral lower extremity joint accommodations during gait
      in anterior cruciate ligament deficient subjects and uninjured controls. DESIGN:
      Gait testing of 10 chronic anterior cruciate ligament deficient subjects prior to
      and 3 months following reconstructive surgery, and 10 uninjured controls.
      BACKGROUND: It is possible that bilateral joint accommodations could occur as a
      result of anterior cruciate ligament injury and in response to surgical repair.
      Few studies have investigated bilateral joint accommodations to anterior cruciate
      ligament injury and there is little consistency in the reported results. METHODS:
      Bilateral lower extremity kinematic and kinetic data were collected from 12
      walking trials and inverse dynamics calculations were made to estimate bilateral
      knee and hip joint angle, moment, and power patterns during the stance phase of
      gait. RESULTS: Control subjects exhibited asymmetrical hip but symmetrical knee
      joint moment and power patterns. In contrast, the anterior cruciate ligament
      deficient subjects exhibited symmetrical hip and asymmetrical knee joint moment
      and power patterns prior to and following reconstructive surgery. CONCLUSIONS:
      Gait asymmetry in healthy subjects should not be considered pathological. In
      addition, chronic anterior cruciate ligament injury results in joint specific,
      bilateral lower extremity accommodations in gait mechanics. These accommodations
      persist 3 months following surgical repair.

PMID- 14967577
TI  - Gender differences in three dimensional gait analysis data from 98 healthy Korean
      adults.
AB  - OBJECTIVES: The research hypothesis was that healthy adults would walk
      differently according to their gender when walked barefoot at their comfortable
      speed. The aim of this study was to prove the hypothesis in healthy Korean
      adults. DESIGN: Between-gender statistical comparisons of the gait analysis data
      including spatiotemporal, three-dimensional joint kinematic and kinetic data.
      BACKGROUND: There have been few attempts to identify the significant gender
      differences in gait pattern and to explore their possible causes. METHODS:
      Healthy 98 Korean adults (47 females and 51 males) volunteered. Gait analysis
      data was obtained with opto-electric system and force plates. Normalization was
      used to avoid the body size effect. Gender difference was tested with independent
      t-test, ancova, and two-way repeated anova. RESULTS: Females were shorter, both
      in height and leg length ( P < 0.05 ). The cadence and pelvic width were as great
      as in males. They walked slower than males due to shorter stride length ( P <
      0.05 ). The females had still shorter stride length and narrower step width ( P <
      0.05 ), and they walked as fast as the males. Females walked with their pelvis
      tilted more anteriorly and more up and down oblique motion, hip joints more
      flexed-adducted-internally rotated, knee joint in more valgus angles ( P = 0.05
      ). CONCLUSIONS: The gait analysis data had significant gender differences. We
      assume that the difference is due to gender features of the gait-related anatomy
      and habits. Comparison with other research shows some evidence for racial
      differences.

PMID- 14967578
TI  - Analysis of passive motion characteristics of the ankle joint complex using dual
      Euler angle parameters.
AB  - OBJECTIVE: To apply the dual Euler angles method to investigate the passive
      motion characteristics of the human ankle joint complex. DESIGN: Three
      dimensional kinematic data of the ankle joint complex was collected from 10 knee
      below foot cadaver specimens. BACKGROUND: Besides the Euler angles and screw axis
      methods, the dual Euler angles method has been proposed as an alternative
      approach to quantify general spatial human joint motion. The dual Euler angles
      method provides a way to combine rotational and translational joint motions and
      to interpret motions in Cartesian coordinate systems, which can avoid the
      problems caused by the use of the joint coordinate system due to non
      orthogonality. METHODS: A non-metal experimental setup was fabricated to generate
      motion in foot cadaver specimens. The kinematic data during passive dorsiflexion
      plantarflexion was measured using an electromagnetic tracking device. RESULTS:
      The kinematic coupling characteristics and the respective contribution of the
      ankle joint and the subtalar joint to the gross motion of the foot with respect
      to the shank were analyzed based on dual Euler angle parameters. The results
      obtained in this study are generally in agreement with the observations reported
      previously. CONCLUSIONS: The dual Euler angles method is suitable for analyzing
      the motion characteristics of the ankle joint complex. The motion at the ankle
      joint complex involves rotations about and translations along three axes.

PMID- 14967579
TI  - The effect of posterior tibialis tendon dysfunction on the plantar pressure
      characteristics and the kinematics of the arch and the hindfoot.
AB  - OBJECTIVE: To study posterior tibialis tendon dysfunction using an in vitro model
      of the foot and ankle during the heel-off instant of gait. BACKGROUND: Previous
      studies have concentrated primarily on the effect of posterior tibialis tendon
      dysfunction on the kinematics of the hindfoot and the arch. METHODS: The
      specimens were loaded using a custom designed axial and tendon loading system and
      the location of the center of pressure was used to validate heel-off. Arch
      position, hindfoot position and plantar pressure data were recorded before and
      after the posterior tibialis tendon was unloaded. These data were recorded with
      the ligaments intact and after creating a flatfoot deformity. RESULTS: Unloading
      the posterior tibialis tendon caused significant posterior movement in the center
      of pressure for the intact and flatfoot conditions. This also resulted in a
      medial shift in the force acting on the forefoot. The forefoot loads shifted
      medially after a flatfoot was created even when the posterior tibialis tendon
      remained loaded. The spatial relationships of the bones of the arch and the bones
      of the hindfoot also changed significantly for the intact specimen, and to a
      lesser extent after a flatfoot. CONCLUSIONS: The posterior tibialis tendon plays
      a fundamental role in shifting the center of pressure anteriorly at heel-off.
      Posterior tibialis tendon dysfunction causes posterior shift in the center of
      pressure and abnormal loading of the foot's medial structures. This may be the
      reason that posterior tibialis tendon dysfunction leads to an acquired flatfoot
      deformity. Conversely, flatfoot deformity may be a predisposing factor in the
      onset of posterior tibialis tendon dysfunction. This tendon also acts to lock the
      bones of the arch and the hindfoot in a stable configuration at heel-off, but a
      flatfoot deformity compromises this ability.

PMID- 14967580
TI  - Can the increase of bone mineral density following bisphosphonates treatments be
      explained by biomechanical considerations?
AB  - OBJECTIVE: We hypothesized that bone mineral density increase following
      bisphosphonates treatments may be explained by the influence of the drug on the
      mechanical bone remodeling parameters. BACKGROUND: Patients treated with
      bisphosphonates continuously increase their bone mineral density. This increase
      is explained in the first 12-18 months following the treatment by the filling of
      the transient remodeling deficit. Recently, results of a clinical study of
      alendronate treatment over 7 years still show a continuous increase of bone
      mineral density. These results raised several questions regarding our
      understanding of bisphosphonates mode of action. METHODS: Bone remodeling is
      influenced by different factors including mechanical forces. In the present
      study, we propose then to consider the effect of bisphosphonates also under
      biomechanical considerations. RESULTS: Identification of the model with the
      clinical data showed that daily treatment of 10 and 20 mg alendronate decreased
      the bone turnover rate by 2% and 11%, respectively, in comparison with the 5 mg
      alendronate treatment. Moreover, the alendronate treatments decreases the
      resorption threshold stimulus by 19% (25%, 28%) for the 5 mg (10 and 20 mg,
      respectively) compared to placebo. CONCLUSIONS: The increase of bone mineral
      density following bisphosphonates treatment may then be explained by
      biomechanical considerations. Based on this description, bisphosphonates
      treatment may indeed change the susceptibility of bone to its biomechanical
      environment decreasing the mechanical threshold where bone should undergo
      resorption.

PMID- 14967581
TI  - Radiofrequency probe treatment for subfailure ligament injury: a biomechanical
      study of rabbit ACL.
AB  - OBJECTIVE: Utilizing a rabbit anterior cruciate ligament model of ligamentous
      subfailure injury, biomechanical properties of injured ligament treated with
      radiofrequency energy were evaluated. It was hypothesized that an injured
      ligament treated with radiofrequency probe would demonstrate restoration of
      biomechanical properties lost through injury. BACKGROUND: Radiofrequency probe,
      thermal treatment has been utilized in the clinical setting to address joint
      instability caused by ligamentous laxity from injury or repetitive microtrauma.
      The biomechanical effects of radiofrequency probe thermal treatment on injured
      ligamentous tissues have not been studied in the laboratory. DESIGN: Three groups
      of specimens: Control, Sham, and Treatment, 10 each, were tested under identical
      conditions. METHODS: Viscoelastic behavior was analyzed using a relaxation test
      (6% strain, up to 180 s) performed before injury, after injury, and after injury
      plus sham or injury plus radiofrequency probe treatment. RESULTS: After injury
      the normalized forces in the relaxation test decreased by approximately 50%. The
      post-treatment relaxation test revealed significant ( P < 0.01 ) restoration of
      the average relaxation force in the Treatment group to that of the Control group
      (0.79, SD 0.11 vs. 0.80, SD 0.10). Both of these groups were significantly
      different from the Sham group (0.44, SD 0.11). Additionally, stretch-to-failure
      test showed partial restoration of the toe region of the load-deformation curve
      by the radiofrequency treatment. CONCLUSIONS: The radiofrequency probe treatment
      is shown to be an effective mechanism for restoring initial ligament tensile
      stiffness and viscoelastic characteristics lost by the subfailure injury in
      vitro.

PMID- 14967582
TI  - Comparative effects of monopolar radiofrequency energy and conservative
      management of mechanical properties of elongated lateral collateral ligament in
      rabbits: an experimental study.
AB  - OBJECTIVE: We examined the biomechanical effects of shrinkage in elongated rabbit
      lateral collateral ligament. DESIGN: This study was designed in an attempt to
      evaluate the energy effects of monopolar radiofrequency on strained but not
      ruptured ligaments. BACKGROUND: In treatment of ligament injuries difficulty in
      reducing increased laxity after trauma and recurrence of instability are
      important factors for failure. METHODS: Ligament elongation and laxity were
      achieved in operating room by applying varus stress for multiple times. In Group
      C ( n = 8 ), elongated lateral collateral ligaments were treated only with above
      knee cast, while in Group S ( n = 8 ), they were treated with shrinkage and above
      knee casts. The un-operated sides were labeled as control groups. At the 12th
      week after surgery the animals were sacrificed and hind limbs were
      disarticulated. Removing the other soft tissues around knee, only lateral
      collateral ligaments were left intact. Biomechanical analyses of the effects of
      two different treatment methods were compared by performing a pulling-out test.
      RESULTS: Considering maximum load and stiffness, conservatively treated ligaments
      were stronger and stiffer than shrunken ligaments ( P < 0.05 ). CONCLUSION:
      Biomechanical values were altered by both treatment methods. Reflecting an
      alteration in intra-molecular structure, the main alteration was the decrease of
      strength in shrunken ligaments. In ligament injuries, we concluded shrinkage not
      to be superior to conservative treatment.

PMID- 14967583
TI  - Personalized biomechanical simulations of orthotic treatment in idiopathic
      scoliosis.
AB  - OBJECTIVES: To analyse patient-specific bracing biomechanics in the treatment of
      scoliosis. DESIGN: Two complementary computer tools have been developed to
      quantify the brace action on scoliotic spine from pressure measurements, and to
      simulate its effect on patient-adapted finite element model. BACKGROUND: Brace
      pad forces and brace effect on spine deformities have been reported. However, the
      brace mechanisms still need to be better understood to obtain more effective
      treatments. METHODS: The 3D geometry of the spine and rib cage of three scoliotic
      adolescents treated by the Boston brace was obtained using a multiview
      radiographic reconstruction technique. A personalized biomechanical model was
      constructed for each patient. Pressures generated by the brace on the thorax were
      measured using pressure sensors. For each zone with a threshold pressure higher
      than 30 mmHg, a total equivalent force was calculated and applied to the
      corresponding model nodes. RESULTS: The pressure were generally scattered on the
      overall torso, with the highest pressures measured on five distinct regions:
      right thoracic, left lumbar, abdominal, right and left sides of the pelvis. The
      equivalent forces were of 18-73 N. Differences between simulated deformed shapes
      and real in-brace geometry of the patients were less than 6 and 9.8 mm for the
      vertebral positions in the coronal and sagittal planes, and 7.7 degrees for the
      Cobb angles. CONCLUSION: The results supported the feasibility of such approach
      to analyse patient-specific bracing biomechanics, which may be useful in the
      design of more effective braces.

PMID- 14967584
TI  - Choosing EMG parameters: comparison of different onset determination algorithms
      and EMG integrals in a joint stability study.
AB  - OBJECTIVE: The aim was to test various algorithms for onset determination and
      compare onset repeatability to that from integrals of the EMG signal. The
      information contained in both parameters is discussed. DESIGN: Onset times were
      calculated using six different algorithms. The integral of the EMG signal was
      calculated for seven intervals: from tilt start and from each of the resulting
      onsets to 200 ms after tilt start. BACKGROUND: EMG onset times are often
      utilised, especially regarding co-ordination patterns or joint stability. There
      are almost as many different procedures for onset determination as authors
      dealing with it. Results in the literature are contradictory. The determination
      and usage of onset times remains controversial. METHODS: EMG signals from six
      muscles of the lower leg of 23 subjects were recorded during three consecutive,
      expected and unexpected sudden inversion and eversion trials while standing on a
      tilting platform. RESULTS: In most cases the repeatability of the onset times was
      considerably lower than that of the integrals of the EMG for all studied
      algorithms. In some cases earlier onset times corresponded to lower integral
      values and constant onsets to variable integrals. CONCLUSIONS: In many cases
      onset times alone are not sufficient for describing onset phenomena. The
      additional calculation of the integrated EMG might provide relevant information
      regarding the quality of early activation.

PMID- 14967585
TI  - Prediction of tissue decompression in orbital surgery.
AB  - OBJECTIVE: A method to predict the relationships between decompressed volume of
      orbital soft tissues, backward displacement of globe after osteotomy, and force
      exerted by the surgeon, was proposed to improve surgery planning in exophthalmia
      reduction. DESIGN: A geometric model and a poroelastic finite element model were
      developed, based on computed tomography scan data. BACKGROUND: The exophthalmia
      is characterized by a protrusion of the eyeball. Surgery consists in an osteotomy
      of the orbit walls to decompress the orbital content. A few clinical observations
      ruling on an almost linear relationship between globe backward displacement and
      tissue-decompressed volume are described in the literature. METHODS: Fast
      prediction of decompressed volume is derived from the geometric model: a sphere
      in interaction with a cone. Besides, a poroelastic finite element model involving
      morphology, material properties of orbital components and surgical gesture was
      implemented. RESULTS: The geometric model provided a better decompression volume
      estimation than the finite element model. Besides, the finite element model
      permitted to quantify the backward displacement, the surgical gesture and the
      stiffness of the orbital content. CONCLUSIONS: The preliminary results obtained
      for one patient, in accordance with the clinical literature, were relatively
      satisfying. An efficient aid for location and size of osteotomies was derived and
      seemed to be able to help in the surgery planning.

PMID- 14967586
TI  - Associations between serum markers of collagen metabolism and spinal shrinkage.
AB  - OBJECTIVES: To explore whether serum concentrations of the carboxyterminal
      propeptide of type I collagen and the carboxyterminal telopeptide region of type
      I collagen as biomarkers of the metabolic condition of spinal tissues are
      associated with spinal shrinkage as a measure of tissue response to physical
      loading. DESIGN: Association of biomarker concentrations in blood and spinal
      shrinkage in healthy young nurses. BACKGROUND: Certain biomarkers of type I
      collagen metabolism may be considered potential instruments to assess the
      biochemical condition of spinal tissues and alterations thereof in response to
      physical loading. Correlation of the serum concentrations of the biomarkers with
      spinal shrinkage, as a measure of the response of spinal tissues to physical
      loading, provides information on the validity of the biomarkers. METHODS:
      Concentrations of biomarkers of type I collagen synthesis and degradation have
      been monitored during a period of six months in 25 young nurses. Spinal shrinkage
      was assessed on a representative working day and related to shrinkage on a rest
      day. RESULTS: Larger relative spinal shrinkage was associated with a lower rate
      of collagen turnover and a higher relative synthesis. CONCLUSIONS: These results
      support the assumption that biomarkers of type I collagen metabolism are
      associated with structural and material properties of spinal tissues.

PMID- 14967587
TI  - Quantitative arthroscopic ultrasound evaluation of living human cartilage.
AB  - OBJECTIVE: To investigate whether living human articular cartilage can be
      evaluated quantitatively by means of a new diagnostic technique that introduces
      an ultrasonic probe into the knee joint under arthroscopy and then analyzes the A
      mode echogram by means of wavelet transformation. DESIGN: Intact and injured
      sites of living human articular cartilage were evaluated under arthroscopy. The
      maximum magnitude and the echo duration (defined as the length of time that
      included 95% of echo signal) were selected as the quantitative indices on the
      wavelet map. BACKGROUND: Quantitative evaluation of articular cartilage in situ
      has the potential to contribute to our understanding of cartilage breakdown and
      to the effectiveness of cartilage regeneration. However, a reliable method of
      quantitative cartilage evaluation has yet to be developed for clinical use.
      METHODS: Living human articular cartilage was analyzed using an ultrasonic probe
      under arthroscopy and the cartilage characteristics on the echo duration-maximum
      magnitude graph were examined. RESULTS: Unlike the L-shape distribution of human
      cadaver cartilage data, the distribution of the living human articular cartilage
      data showed a smooth curve with a steep initial gradient that flattens gradually
      at the highest value of echo duration on the echo duration-maximum magnitude
      graph. CONCLUSIONS: The present study suggests a new quantitative evaluation
      system for articular cartilage with clinical potential.

PMID- 14967592
TI  - Ultrastructural examination and technical developments.

PMID- 14967593
TI  - Qualitative and quantitative analysis of the effects of acetaminophen and N
      acetylcysteine on the surface morphology of Hep3B hepatoma cells in vitro.
AB  - Acetaminophen (AAP) is harmful to the liver if consumed in excessive doses. Its
      toxicity can be counteracted by N-acetylcysteine (NAC). The authors studied
      cultures of Hep3B cells exposed to AAP or NAC or both, at 24 and 48 h, using the
      scanning electron microscope. Using morphometric software, they found that
      cultures exposed for 24 h to AAP or AAP + NAC suffered reduction in cell
      confluence. Exposure increased the incidence of rounding cells and of apoptotic
      and autoschizic appearances. Differences between control cultures cultivated
      without serum versus those exposed to xenobiotics were merely quantitative, not
      essential.

PMID- 14967594
TI  - Agarose cell block: innovated technique for the processing of urine cytology for
      electron microscopy examination.
AB  - Easy manipulation and preservation of cells in suspension through the different
      steps of sample processing for electron microscopy examination is essential for
      proper diagnosis. The author used agarose gel as an embedding media for
      processing cells in suspension for electron microscopic examination. The AgarCyto
      cell block procedure of Kerstens et al. (J Histochem Cytochem. 2000; 48: 709-
      718) was used to begin electron microscopic processing of exfoliated urothelial
      cells in voided urine or cells in suspension. Processing of agarose cell block
      simultaneously for light and electron microscopic examination represents a great
      advantage offered by this innovated technique.

PMID- 14967595
TI  - Microbial biofilms in the gut: visualization by electron microscopy and by
      acridine orange staining.
AB  - The expression of colonization factors by gut bacteria, the growth rate of gut
      bacteria, and the rate of plasmid exchange by gut bacteria indicate that biofilms
      are a normal component of bacterial growth in the large bowel. Further, in vitro
      experiments demonstrate that growth of normal enteric bacteria in biofilms can be
      facilitated by secretory IgA (SIgA) and by mucins, 2 major components of the gut
      milieu. However, biofilms have not been previously observed in the normal gut. In
      this study, bacterial colonies characteristic of biofilms were observed by
      electron microscopy in normal rat, baboon, and human gut by electron microscopy.
      Confirming these results, acridine orange staining of flash-frozen tissues
      revealed biofilms in the mucus lining along normal gut epithelium.
      Immunofluorescenct microscopy supported this finding and demonstrated an
      association between IgA and the biofilms. These findings provide direct evidence
      that biofilms are present and may play an important role in the commensal
      relationship between enteric bacteria and their hosts. Hematoxylin and eosin
      staining of formalin-fixed tissues resulted in dissociation of the luminal
      contents from the epithelium, suggesting that the association between biofilms
      and the gut epithelium is sensitive to some conditions used to preserve tissue
      for histologic evaluation.

PMID- 14967596
TI  - A novel method for "Wet" SEM.
AB  - Progress in the processing of wet tissues, without the need of fixation and
      complex preparation procedures, may facilitate the microscopic examination of
      tissues and cells. Microscopic examination of tissues is a central tool in
      clinical diagnosis as well as in diverse areas of research. The authors present
      the application of Wet SEM, a technology for imaging fully hydrated samples at
      atmospheric pressure in a scanning electron microscope (SEM). The technique is
      based on 2 principles. First, samples are imaged in sealed specimen capsules and
      are separated from the evacuated interior of the electron microscope by a thin,
      electron-transparent partition membrane that is strong enough to sustain a 1-atm
      pressure difference. Second, imaging is done in a SEM, based on detection of
      backscattered electrons, which penetrate a few microns into the specimen and thus
      give information on the cellular level.

PMID- 14967597
TI  - Glomerulocystic kidney disease in a Belgian Malinois dog: an ultrastructural,
      immunohistochemical, and lectin-binding study.
AB  - Renal cysts in the cortex of a juvenile Belgian Malinois dog with acute renal
      failure were studied by means of light, scanning and transmission electron
      microscopy, immunohistochemistry for intermediate filaments, and binding for
      wheat germ agglutinin (WGA), peanut agglutinin (PNA), and Maclura pomifera
      agglutinin (MPA) lectins to determine the morphological and histochemical
      features of the epithelial cells of these cysts. The cysts were renal corpuscles
      with expanded urinary space. Glomerular tufts were small with poorly developed
      capillary loops and increased mesangial matrix. Continuity with the proximal
      tubule was evident in some cystic glomeruli. Two cell types lined Bowman's
      capsule. One was squamous with a central cilium and microvilli. The other had
      morphological and histochemical features of immature podocytes (parietal
      podocytes). These cells were round and protruded into the urinary space; they had
      thick cytoplasmic projections that resembled foot processes of podocytes,
      microvilli, and filtration slits. The parietal podocytes expressed vimentin and
      cytokeratins and had affinity for WGA as do normal immature podocytes. These
      features suggest that the parietal podocytes are derived by metaplasia of the
      parietal cells. The basement membrane of Bowman's capsule was irregularly
      thickened and showed multifocal glycosylation changes with lectin histochemistry
      (WGA, PNA, MPA) in areas adjacent to the parietal podocytes. Histologic and
      ultrastructural findings in this dog are consistent with glomerulocystic kidney
      disease. This is the second report of canine glomerulocystic kidney disease.
      Features are similar to those of the human counterpart, but it is unclear whether
      genetic defects cause the disease in the dog. The presence of parietal podocytes
      in all cysts suggests that abnormal differentiation may play an important role in
      the pathogenesis of this type of polycystic kidney disease.

PMID- 14967598
TI  - The problematic issue of Kufs disease diagnosis as performed on rectal biopsies:
      a case report.
AB  - Kufs disease, the late-onset form of a group of neurodegenerative disorders,
      known as the neuronal ceroid-lipofuscinoses, is characterized by
      intraneuronal/extraneuronal accumulation of proteins that are visible as
      fingerprint inclusions and granular osmiophilic deposits (GRODs) at the
      ultrastructural level. A problematic case of Kufs disease in a 53-year-old female
      affected by progressive gait disturbances, myoclonus, epilepsy, and profound
      dementia is presented. Laboratory, biochemical, and molecular genetic tests were
      unremarkable. A magnetic resonance imaging of the brain revealed a moderate
      atrophy over both hemispheres with no white matter changes. Ultrastructural
      examination of rectal mucosa biopsies showed fingerprint inclusions in
      perivascular smooth muscle cells. Pathological examination of autoptic tissues
      showed numerous intraneuronal PAS-positive, diastase-resistant inclusions
      corresponding to GRODs at the ultrastructural examination, but no fingerprint
      inclusions. Cerebellum, skeletal, and cardiac muscles, skin, and liver were
      unaffected. The present case illustrates the diagnostic difficulties encountered
      while examining Kufs disease pathological samples. Main problematic issues
      include (1) specificity and diagnostic value of fingerprint inclusions when found
      exclusively in perivascular smooth muscle cells; (2) safe distinction of GRODs
      from lipofuscin inclusions in cerebral tissue; and (3) reliability in using
      extraneural tissues and, in particular, rectal mucosa biopsies for diagnostic
      purposes.

PMID- 14967599
TI  - Soft-tissue extrarenal rhabdoid tumor with a unique long-term survival.
AB  - Rhabdoid tumors of kidney and extrarenal rhabdoid tumors are identified by a
      round-epithelioid cell morphology and a bland immunophenotype, but a distinctive
      ultrastructure dominated by paranuclear whorls of intermediate filaments, most
      usually of vimentin. These tumors are also known to be highly aggressive
      malignancies, which, typically, bear a poor prognosis, frequently measured in
      months following initial presentation. The authors record the case a soft-tissue
      rhabdoid tumor in a 12-year-old boy with a unique long-term survival in excess of
      16 years. The features of this case are documented, with a brief summary of
      histological, immunohistochemical, ultrastructural, and genetic characteristics
      of this entity.

PMID- 14967600
TI  - Effects of cigarette smoke exposure and cessation on inflammatory cells and
      matrix metalloproteinase activity in mice.
AB  - B6C3F1 female mice were exposed to cigarette smoke (CS) (250 mg/m3 total
      particulate material) or filtered air (FA), 6 hours/day, 5 days/week, for 6, 7,
      or 10 weeks, or to CS for 6 weeks, then FA for 1 or 4 additional weeks. Exposure
      to CS increased macrophages, neutrophils, lymphocytes, and matrix
      metalloproteinase (MMP)-2 and MMP-9 content in bronchoalveolar lavage fluid.
      Partial recovery of most lavage parameters (except lymphocytes) was observed 1
      week after cessation of CS exposure with further reductions after 4 weeks, but
      interstitial inflammation persisted longer. These results support a role for MMPs
      in CS-induced emphysema and indicate that smoking cessation allows restoration
      toward normal homeostasis.

PMID- 14967601
TI  - Interaction between mycobacteria and mucus on a human respiratory tissue organ
      culture model with an air interface.
AB  - Mycobacteria adhere specifically to extracellular matrix (ECM) and mucus with a
      fibrous, but not globular, appearance, in organ cultures of human respiratory
      mucosa examined by scanning electron microscopy. Previously, light microscopy
      sections made of tissue infected for 7 days demonstrated mycobacteria associated
      with mucus on the organ culture surface, and within submucosal glands in areas of
      damaged epithelium. The authors have now investigated the interactions between
      Mycobacterium avium complex (MAC), Mycobacterium tuberculosis (MTB), and
      Mycobacterium smegmatis (MS) and mucus by preincubating bacteria with purified
      mucins MUC5AC and MUC5B prior to inoculation onto the organ culture mucosal
      surface. They have also measured mucin production by the organ culture after
      mycobacterial infection. Mucus did not cause clumping of mycobacteria. There was
      a significant (P=.03) increase in the amount of fibrous mucus, but not globular
      mucus, observed on tissue inoculated with mucins compared to controls. The number
      of bacteria adhering to ECM was markedly reduced after incubation with mucins,
      which could indicate a protective effect. Mycobacterial infection did not
      increase mucin production by the organ culture. Mycobacterial adherence to mucins
      may play a role in the pathogenicity of mycobacteria in diseases such as cystic
      fibrosis, bronchiectasis, and chronic obstructive pulmonary disease (COPD), in
      which there are changes in mucus composition and clearance.

PMID- 14967602
TI  - Acute cardiopulmonary effects of a dual-endothelin receptor antagonist on oleic
      acid-induced pulmonary arterial hypertension in dogs.
AB  - The objective of this study was to evaluate the cardiopulmonary effects of a dual
      endothelin (ET) receptor antagonist, Tezosentan, on oleic acid (OA)-induced acute
      lung injury with pulmonary arterial hypertension in dogs. Twelve pentobarbital
      anesthetized dogs with intravenous OA-induced acute lung injury (ALI) were
      divided into 2 groups. The control group (n=6) received saline treatment, whereas
      the treatment group (n=6) received the ET receptor antagonist, Tezosentan (1
      mg/kg intravenous [i.v.]+1 mg/kg/h i.v. infusion). Cardiopulmonary parameters
      were monitored continuously for 1 hour. OA administration resulted in a
      significant increase in mean pulmonary arterial pressure (MPAP) and pulmonary
      vascular resistance (PVR) and a decrease in mean systemic arterial pressure
      (MSAP), systemic vascular resistance (SVR), and cardiac output (CO) in all dogs.
      Tezosentan treatment markedly attenuated the pulmonary hypertension, with a 32%
      decrease in MPAP (from 23 +/- 2 mm Hg to 15 +/- 2 mm Hg; P<.01) and a 22%
      decrease in PVR (from 860 +/- 105 dyn.s.cm(-5) to 670 +/- 96 dyn.s.cm(-5); P<.01)
      at the end of study. MSAP and SVR were unchanged after Tezosentan treatment, and
      there was an increase in cardiac output and a decline in peak inspiratory
      pressure (PIP) in the Tezosentan group compared with the control group. These
      results indicate that the dual-ET receptor antagonist, Tezosentan, can attenuate
      the pulmonary hypertension induced by OA. Thus, dual-ET receptor antagonists such
      as Tezosentan may be useful in the management of acute pulmonary arterial
      hypertension, complicating the course of OA-induced lung injury.

PMID- 14967603
TI  - The effect of respiratory synctial virus on chemokine release by differentiated
      airway epithelium.
AB  - Respiratory synctial virus (RSV) infection of undifferentiated airway epithelial
      cells has been shown to induce the production of chemokines. The purpose of this
      study was to investigate the vectorial release of interleukin (IL-8) and Released
      on Activation, Normal T-cell Expressed and Secreted (RANTES) by polarized, well
      differentiated respiratory epithelial cells after RSV infection. Human bronchial
      epithelial cultures were differentiated under air-liquid interface conditions and
      infected with RSV by the apical or basolateral route. RSV infection was specific
      to the apical surface. Supernatants were collected at 6 and 48 hours after RSV
      inoculation, and IL-8 and RANTES were measured by enzyme-linked immunosorbent
      assay (ELISA). Both IL-8 and RANTES were significantly released by 48 hours
      following inoculation with RSV. The secretion of each chemokine was greatest
      after apical inoculation, and secretion was polarized to the basolateral
      supernatant. Immunohistochemical staining confirmed that RSV infection was
      specific to ciliated cells, and immunohistochemical staining for chemokines was
      localized to RSV-infected ciliated cells. The authors conclude that, in
      differentiated human airway epithelium in vitro, RSV-induced increases in IL-8
      and RANTES release are predominantly in the basolateral direction. In epithelial
      layers, virus-containing cells are the predominant source of the increased
      chemokine release. The authors speculate that similar processes in vivo influence
      recruitment of leukocytes to sites of RSV infection.

PMID- 14967604
TI  - Mucociliary clearance is enhanced in rat models of cigarette smoke and
      lipopolysaccharide-induced lung disease.
AB  - In this study, the authors describe a new technique enabling the rapid assessment
      of mucociliary clearance (MCC) in rats and characterize this aspect of innate
      host defense in 2 animal models of bronchitis. Following instillation into the
      airways, fluorescent microspheres were rapidly cleared over 24 hours, with 60% to
      80% of clearance occurring within 4 hours. On a background of airway neutrophilia
      and mucus hypersecretion, induced by either lipopolysaccharide or cigarette
      smoke, MCC was significantly enhanced. This reserve capacity in the MCC system
      will need to become overwhelmed in order to model the clinically observed
      impairment of lung mucus clearance in an animal system.

PMID- 14967605
TI  - Lung fixation for the preservation of air spaces.
AB  - The procedures for the fixation of entire lungs of small rodents are presented
      together with various techniques used to verify the structural integrity of the
      lung tissue. To achieve this, the lungs were dissected out from rats and mice
      killed by ether overdose. The specimens were rinsed with isotonic saline and
      fixation solution under low vacuum conditions. After fixation, they were dried
      using alcohol and stored in a noncollapsed state (i.e., state of inhalation).
      Light and scanning electron microscopy as well as magnetic resonance imaging
      using hyperpolarized 3He were employed to verify the intact state on
      interalveolar septa and walls of smaller bronchi as well as accessibility of the
      air spaces.

PMID- 14967606
TI  - Frost tolerance and bud dormancy of container-grown yellow birch, red oak and
      sugar maple seedlings.
AB  - Container-grown seedlings of red oak (Quercus rubra L.), sugar maple (Acer
      saccharum Marsh.) and yellow birch (Betula alleghaniensis Britton) in their first
      year of growth were overwintered outdoors. Tolerance of roots and stems to
      freezing was compared from late summer to the following spring. Mitotic activity
      in the apical bud was related more closely to air temperature than to bud
      dormancy as defined by days to bud break. In all species, stem hardening was
      observed before days to bud break reached a maximum. Dormancy release (days to
      bud break equal to zero) of yellow birch coincided with loss of stem hardening in
      the spring. Roots hardened more slowly, had a lower frost tolerance than stems in
      fall and winter, and dehardened earlier than stems in the spring. There were
      differences in stem and root hardiness among the species, with yellow birch being
      the most tolerant, followed by sugar maple and red oak. Primarily because of root
      sensitivity to frost, winter was a critical period for all three species, but
      particularly for red oak.

PMID- 14967607
TI  - Steady-state nutrition of Pinus resinosa seedlings: response to nutrient loading,
      irrigation and hardening regimes.
AB  - To test effects of fertilization on late-season growth and nutrient content of
      container-grown red pine (Pinus resinosa Ait.), seedlings were subjected to a
      factorial combination of two fertilization regimes (exponentially increasing
      concentrations providing 25 (1N) and 75 (3N) mg N seedling(-1), respectively) and
      two irrigation regimes (well-watered and water-stressed) followed by drought
      hardening or nonhardening. The fertilization treatments gave rise to steady-state
      nutrition in the seedlings during the prehardening phase. The 3N treatment
      increased macronutrient uptake significantly more than dry matter production,
      particularly in the roots, giving rise to what has been called luxury consumption
      of nutrients, or nutrient loading. Nutrient loading was higher in well-watered
      seedlings than in water-stressed seedlings. Among well-watered seedlings,
      relative growth rate of nutrient-loaded seedlings was more sensitive to drought
      during the hardening phase than that of nonloaded seedlings. However, when
      watering was resumed at the end of the hardening treatment, the relative growth
      rate of the nutrient-loaded seedlings (421%) exceeded that of the nonloaded
      seedlings (213%). Nitrogen accumulation was also higher in nutrient-loaded
      seedlings than in nonloaded seedlings during the post-hardening phase.

PMID- 14967608
TI  - Effect of elevated temperatures on carbon dioxide exchange in Picea rubens.
AB  - We examined some of the physiological reasons that may underlie past and expected
      future migrations of red spruce (Picea rubens Sarg.) by evaluating the effects of
      high temperatures on photosynthesis and respiration of trees growing on Whiteface
      Mountain, NY. At temperatures of 35-40 degrees C, the trees exhibited a zero or
      negative carbon balance. Higher temperatures resulted in cellular disorganization
      and death. Temperatures around 30 degrees C resulted in reduced CO(2) uptake, a
      condition that could decrease future reproductive output and competitive stature.
      We conclude that thermal intolerance explains, at least in part, the absence of
      red spruce at low elevations and latitudes where temperatures of >/= 30 degrees C
      occur. We suggest that the thermosensitivity of this species is important with
      respect to global climate trends and migration patterns.

PMID- 14967609
TI  - Seasonal patterns of light-saturated photosynthesis and leaf conductance for
      mature and seedling Quercus rubra L. foliage: differential sensitivity to ozone
      exposure.
AB  - Extrapolation of the effects of ozone on seedlings to large trees and forest
      stands is a common objective of current assessment activities, but few studies
      have examined whether seedlings are useful surrogates for understanding how
      mature trees respond to ozone. This two-year study utilized a replicated open-top
      chamber facility to test the effects of subambient, ambient and twice ambient
      ozone concentrations on light-saturated net photosynthesis (P(max)) and leaf
      conductance (g(l)) of leaves from mature trees and genetically related seedlings
      of northern red oak (Quercus rubra L.). Gas exchange measurements were collected
      four times during the 1992 and 1993 growing seasons. Both P(max) and g(l) of all
      foliage followed normal seasonal patterns of ontogeny, but mature tree foliage
      had greater P(max) and g(l) than seedling foliage at physiological maturity. At
      the end of the growing season, P(max) and g(l) of the mature tree foliage exposed
      to ambient ( approximately 80-100 ppm-h) and twice ambient ( approximately 150
      190 ppm-h) exposures of ozone were reduced 25 and 50%, respectively, compared
      with the values for foliage in the subambient ozone treatment ( approximately 35
      ppm-h). In seedling leaves, P(max) and g(l) were less affected by ozone exposure
      than in mature leaves. Extrapolations of the results of seedling exposure studies
      to foliar responses of mature forests without considering differences in foliar
      anatomy and stomatal response between juvenile and mature foliage may introduce
      large errors into projections of the response of mature trees to ozone.

PMID- 14967610
TI  - Photosynthesis and water relations of savanna tree species differing in leaf
      phenology.
AB  - Godmania macrocarpa Hemsley, a deciduous tree characteristic of fire protected
      areas of the savanna region of central Venezuela, was more drought tolerant,
      allocated more N to leaves and had consistently higher photosynthetic rates than
      Curatella americana L., a ubiquitous species growing successfully within the
      grasslands of tropical American savannas. Godmania macrocarpa maintained higher
      leaf conductance and photosynthesized at higher xylem water tensions than C.
      americana. As the dry season progressed, G. macrocarpa was more affected by water
      stress than C. americana, which may explain why G. macrocarpa shed its leaves
      before forming new leaves. For both species, leaf sap osmolality was strongly
      correlated with, but not completely accounted for by, soluble sugars. Integrated
      water-use efficiency, as measured by delta(13)C, was similar for both species,
      but young leaves were more efficient than old leaves. Water-use efficiency of
      adult leaves was similar in both species as a result of higher photosynthetic
      rates in G. macrocarpa and lower leaf conductances in C. americana. Compared to
      G. macrocarpa, instantaneous photosynthetic N-use efficiency was higher in C.
      americana despite its lower maximum photosynthetic rates. The absence of G.
      macrocarpa trees from open grasslands, despite their high productive capacity, is
      possibly the result of unfavorable conditions for germination, poor survival of
      seedlings, and lack of resistance against fire.

PMID- 14967611
TI  - Axial and radial water flow in the trunks of oak trees: a quantitative and
      qualitative analysis.
AB  - Axial water flow in the trunks of mature oak trees (Quercus petraea (Matt.)
      Liebl. and Q. robur L.) was studied by four independent techniques: water
      absorption from a cut trunk, sap flowmeters, heat pulse velocity (HPV) and
      thermoimaging. Estimation of the total water flow with sap flowmeters, HPV and
      water absorption yielded comparable results. We concluded from dye colorations,
      thermograms and axial profiles of sap flow and heat pulse velocity that, in
      intact trunks, most of the flow occurred in the current-year ring, where early
      wood vessels in the outermost ring were still functional. Nevertheless, there was
      significant flow in the older rings of the xylem. Total water flow through the
      trunk was only slightly reduced when air embolisms were artificially induced in
      early-wood vessels, probably because there was little change in hydraulic
      conductance in the root-leaf sap pathway. Embolization of the current-year
      vessels reactivated transport in the older rings.

PMID- 14967612
TI  - Variation in foliar delta(13)C values within the crowns of Pinus radiata trees.
AB  - Although herbaceous species generally show little within plant variation in
      delta(13)C, trees show large spatial and temporal differences. We found that the
      aspect of exposure and branch length accounted for up to 6 per thousand
      delta(13)C difference within the foliage of individual trees of Pinus radiata D.
      Don. The foliage on branches 0.5 m in length was as much as 4 per thousand more
      depleted in (13)C than foliage on 10-m long branches, and an additional 2 per
      thousand more depleted on the shaded side than on the exposed side. We confirmed
      that on clear days, relative branch hydraulic conductivity, defined as the ratio
      of transpiration to the water potential gradient, was much higher in short
      branches than in long branches. Stomatal conductance remained high in foliage on
      short branches during the day, whereas it declined progressively in long-branch
      foliage under similar conditions. These differences were sufficient to explain
      the observed variation in delta(13)C in foliage on long and short branches.

PMID- 14967613
TI  - Influence of climate and fertilization on net photosynthesis of mature slash
      pine.
AB  - Net photosynthesis was measured under field conditions in 23-year-old slash pine
      (Pinus elliottii Engelm. var. elliottii) trees to determine how it was affected
      by fertilization and climate. There was only a small decrease in rates of net
      photosynthesis from late summer through winter demonstrating that appreciable
      carbon gain occurs throughout the year in slash pine. Although fertilization
      substantially increased leaf area and aboveground biomass, it only slightly
      increased the rate of net photosynthesis. Simultaneous measurements of gas
      exchange in fertilized and unfertilized (control) plots allowed the detection of
      a small, but statistically significant difference in average net photosynthesis
      of 0.14 micro mol m(-2) s(-1). Irradiance, and to a lesser extent air
      temperature, were the environmental factors that exerted the most control on net
      photosynthesis. The highest rates of net photosynthesis occurred between air
      temperatures of 25 and 35 degrees C. Because air temperatures were within this
      range for 46% of all daylight hours during the year, air temperature was not
      often a significant limitation. Soil and atmospheric water deficits had less
      effect on photosynthesis than irradiance or air temperature. Although the depth
      to the water table changed during the year from 10 to 160 cm, predawn and midday
      xylem pressure potentials only changed slightly throughout the year. Predawn
      values ranged from -0.63 to -0.88 MPa in the control plot and from -0.51 to -0.87
      MPa in the fertilized plot and were not correlated with water table depth. There
      was no correlation between xylem pressure potentials and net photosynthesis,
      presumably because water uptake was adequate. Although vapor pressure deficits
      reached 3.5 kPa during the summer, they had little effect on net photosynthesis.
      Over a vapor pressure deficit range from 1.0 to 3.0 kPa, net photosynthesis only
      decreased 21%. No differences in responses to these environmental factors could
      be attributed to fertilization.

PMID- 14967614
TI  - Phosphorus supply affects the photosynthetic capacity of loblolly pine grown in
      elevated carbon dioxide.
AB  - Effects of phosphorus supply and mycorrhizal status on the response of
      photosynthetic capacity to elevated CO(2) were investigated in loblolly pine
      (Pinus taeda L.) seedlings. Seedlings were grown in greenhouses maintained at
      either 35.5 or 71.0 Pa CO(2) in a full factorial experiment with or without
      mycorrhizal inoculum (Pisolithus tinctorius (Pers.) Coker & Couch) and with an
      adequate or a limiting supply of phosphorus. Assimilation versus internal CO(2)
      partial pressure (C(i)) curves were used to estimate maximum Rubisco activity
      (V(c,max)), electron transport mediated ribulose 1,5-bisphosphate regeneration
      capacity (J(max)), phosphate regeneration capacity (PiRC) and daytime respiration
      rates (R(d)). Nonmycorrhizal seedlings grown with limiting phosphorus had
      significantly reduced V(c,max) and PiRC compared to seedlings in other
      treatments. Elevated CO(2) increased photosynthetic capacity in nonmycorrhizal
      seedlings in the low phosphorus treatment by increasing PiRC, whereas it induced
      phosphorus limitation in mycorrhizal seedlings in the low phosphorus treatment
      and did not affect the photosynthetic capacity of seedlings in the high
      phosphorus treatment. Despite the variety of effects on photosynthetic capacity,
      seedlings in the elevated CO(2) treatments had higher net assimilation rates than
      seedlings in the ambient CO(2) treatments. We conclude that phosphorus supply
      affects photosynthetic capacity during long-term exposure to elevated CO(2)
      through effects on Rubisco activity and ribulose 1,5-bisphosphate regeneration
      rates.

PMID- 14967615
TI  - Maturation in Douglas-fir: I. Changes in stem, branch and foliage characteristics
      associated with ontogenetic aging.
AB  - Two experiments were conducted to characterize changes associated with
      ontogenetic aging in coastal Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco)
      and to identify possible maturation "markers" for this species. In the first
      experiment (Experiment 1), scions of ages 1, 4 and 9 years were collected from
      four seed zones in field progeny tests and grafted onto 1-year-old rootstocks. In
      Experiment 2, scions from five full-sib families of ages 1 and 10 years were
      collected from one progeny test and similarly grafted. Grafts for both
      experiments were planted in the field in a completely randomized design. The
      grafts were measured after two and six growing seasons. In Experiment 1, graft
      diameter, number of terminal bud flushes per year, number of branches, and branch
      length decreased with age. Plagiotropic angle and needle weight increased. All
      variables except needle length had a significant age x seed zone interaction.
      After 6 years, internodal stem diameters, numbers of nodal and internodal
      branches, and length and diameter of internodal branches decreased with age, and
      there were age x seed zone interactions with most variables. In Experiment 2,
      graft height and diameter, number of flushes, number and size of lateral
      branches, needle length and weight decreased with age. After 6 years, height and
      diameter, size and number of nodal and internodal branches, and leaf chlorophyll
      concentration (measured in April) decreased, but there were relatively few age x
      family interactions. An analysis based on traits that were significantly affected
      by age, but that did not interact with seed zone or family, indicated that main
      stem diameter, nodal branch length and nodal branch diameter were the most
      consistent and reliable maturation markers.

PMID- 14967616
TI  - Maturation in Douglas-fir: II. Maturation characteristics of genetically matched
      Douglas-fir seedlings, rooted cuttings and tissue culture plantlets during and
      after 5 years of field growth.
AB  - Seedlings, rooted cuttings from juvenile stock plants, and cotyledon-derived
      tissue culture plantlets were propagated from several coastal Douglas-fir
      (Pseudotsuga menziesii (Mirb.) Franco) full-sib families so that the rooted
      cuttings and plantlets were clonally identical. The stock types (seedlings,
      rooted cuttings and plantlets) were planted in the field in spring 1987. In fall
      1991, after five complete growing seasons, the plants were measured and these
      values compared to maturation "markers" identified for Douglas-fir in the
      companion paper (Ritchie and Keeley 1994). Nodal branch lengths and nodal branch
      diameters decreased in the order seedlings > rooted cuttings > plantlets. The
      decreases were about 21% for nodal branch lengths and 24% for nodal branch
      diameters. Seedlings carried significantly more total branches (nodal +
      internodal) than the other two stock types. Height growth was similar for the
      three stock types, but plantlet height increment was beginning to decrease during
      the fourth year. We conclude that vegetative propagules of Douglas-fir exhibited
      traits of mature trees. These were particularly marked in the cotyledon-derived
      plantlets.

PMID- 14967617
TI  - Adaptive significance of intermittent shoot growth in Douglas-fir seedlings.
AB  - We tested the hypothesis that intermittent (lammas) shoot growth in Douglas-fir
      (Pseudotsuga menziesii var menziesii (Mirb.) Franco) seedlings from dry regions
      of southwest Oregon is adaptively significant. Seedlings from open-pollinated
      families (160 total) from two inland (dry) and two coastal (wet) sources were
      grown under either well-watered or intermittent drought conditions (temporary
      drought followed by rewatering) for two growing seasons. In the first growing
      season, the results supported the hypothesis: the frequency of a second flush was
      genetically controlled (although weakly, h(f) (2) </= 0.34); more seedlings, on
      average, from inland families than from coastal families displayed a second
      flush; and seedlings from inland families were more responsive to the
      intermittent drought regime in terms of increased frequency of a second flush
      (relative to the frequency in the well-watered regime). During the second growing
      season, the intermittent drought treatment did not promote intermittent shoot
      growth, although inland and coastal families had different patterns of shoot
      growth that reflected adaptations to soil water availability. We conclude that
      inland families have adapted to dry summers and short growing seasons by relying
      predominantly on predetermined growth for seedling height increment after the
      first growing season. In response to wetter and generally longer growing seasons,
      however, coastal families have developed a less regulated pattern of shoot
      extension and rely more on free growth.

PMID- 14967618
TI  - Photosynthesis of a tropical canopy tree, Ceiba pentandra, in a lowland forest in
      Panama.
AB  - Diel (24 h) courses of CO(2) and water-vapor exchange of Ceiba pentandra (L.)
      Gaertn. (Bombacaceae) were studied under natural tropical conditions in the semi
      evergreen moist forest of Barro Colorado Island, Panama. Measurements were
      conducted from early February 1991 (dry season), shortly after new leaves
      emerged, until mid-October 1991 (wet season), when leaves were shed. Rates of net
      CO(2) uptake were significantly higher in the dry season than in the wet season,
      and showed a linear decrease with leaf age. Leaf nitrogen concentrations and
      contents also decreased with age. Our estimate of annual carbon gain (2640 g
      CO(2) m(-2) year(-1) or 21 g CO(2) g(DW) (-1) year(-1)) is considerably higher
      than estimates available for temperate forest trees.

PMID- 14967619
TI  - Floral induction in Eucalyptus nitens.
AB  - Eucalyptus nitens (Deane & Maiden) Maiden takes at least five years to initiate
      flower buds from seed and is an infrequent and light flowerer. Because this
      behavior constitutes a major impediment to breeding programs, we examined the
      mechanisms controlling floral induction in E. nitens, with the long-term aim of
      reducing generation time and increasing seed yield. Application of paclobutrazol
      reduced the concentration of endogenous gibberellic acid (GA) in apical tissue
      and enhanced the reproductive activity of grafted trees maintained outside over
      winter in Canberra, Australia. Grafts maintained in a warm greenhouse over winter
      did not produce flower buds, despite the paclobutrazol-induced reduction in GA
      concentration of the apical tissue. Exposing untreated grafts, which had been
      maintained over winter in a warm greenhouse, to low temperature the following
      spring reduced growth but did not induce flower bud production. Addition of GA(3)
      to paclobutrazol-treated grafts reduced the effect of paclobutrazol on
      reproductive activity.

PMID- 14967620
TI  - Differentiation of poplar and willow clones using RAPD fingerprints.
AB  - The technique of random amplified polymorphic DNA (RAPD) fingerprinting was used
      to differentiate species and identify clones of 15 poplar and 15 willow clones
      (ramets of three poplar clones were also included to verify the stability of the
      results). Four random DNA primers (Deca-11, Chl-1, Chl-4 and Chl-10) and an M13
      universal primer were used to determine DNA polymorphism among the clones. Based
      on the DNA banding pattern obtained with the four DNA primers by polymerase chain
      reaction (PCR) amplification we conclude that RAPD fingerprinting with properly
      selected primers can be used for clonal and species differentiation of poplar and
      willow. The technique is simple, accurate and inexpensive.

PMID- 14967621
TI  - Fall acclimation patterns of interior spruce seedlings and their relationship to
      changes in vegetative storage proteins.
AB  - Changes in the content of vegetative storage proteins (VSPs) were monitored in 1
      year-old interior spruce (Picea glauca (Moench) Voss x Picea engelmanni Parry
      complex) seedlings from late summer until midwinter. Seedlings were also
      monitored for days to terminal bud break (DBB(t)), dry weight fraction and frost
      hardiness, measured as both index of injury at -18 degrees C (IL(-18 degrees C))
      and as the temperature causing 50% foliage electrolyte leakage (LT(50)). During
      fall acclimation, VSP content, frost hardiness and dry weight fraction increased,
      whereas DBB(t) decreased. In mid-November, IL(-18 degrees C) reached its lowest
      value, coinciding with high VSP content and dry weight fraction, and low DBB(t).
      The LT(50) decreased in a linear manner as dry weight fraction and VSP content
      increased; r(2) values were 0.69 to 0.81, respectively. The fall accumulation of
      VSPs was also highly correlated with increased dry weight fraction. The increase
      in VSP content occurred as seedling photosynthetic capacity declined, but maximum
      contents were obtained before complete inactivation of the photosynthetic
      apparatus. The results indicate that VSP accumulation is an integral part of fall
      acclimation in interior spruce, closely parallels frost hardiness and partially
      accounts for the increase in dry weight fraction.

PMID- 14967622
TI  - Boric acid-phenolic relationships within the Pinus echinata-Pisolithus tinctorius
      ectomycorrhizal association.
AB  - At germination, container-grown shortleaf pine seedlings were inoculated with
      Pisolithus tinctorius (Pers.) Coker & Couch or left uninoculated, and both groups
      were fertilized semiweekly with a modified Hoagland's solution supplemented with
      0 or 0.4 mM boric acid. After 12, 16 and 24 weeks, seedling root tissue was
      analyzed for ectomycorrhizal colonization, phenolic concentration and
      phenoloxidase activity. In addition, phenoloxidase activity was assayed in P.
      tinctorius that had been cultured in a liquid medium containing boric acid.
      Inoculation with P. tinctorius increased the root phenolic concentration of 16-
      and 24-week-old seedlings, and increased root phenoloxidase activity in 12-, 16-
      and 24-week-old seedlings. Fertilization with boric acid reduced the phenolic
      concentration of P. tinctorius ectomycorrhizae after 24 weeks. Although boric
      acid fertilization did not affect the phenoloxidase activity of 12-, 16- and 24
      week-old inoculated roots, or that of 16- and 24-week-old uninoculated roots, it
      increased the phenoloxidase activity of P. tinctorius grown in vitro and 12-week
      old uninoculated roots. We conclude that boric acid fertilization influences the
      phenolic relations of the shortleaf pine-P. tinctorius ectomycorrhizal
      association, possibly through a boric acid-induced increase in phenoloxidase
      activity.

PMID- 14967623
TI  - Diurnal variation in leaf extension of Salix viminalis at two nitrogen supply
      rates.
AB  - To investigate how nitrogen supply might affect the biophysical factors
      controlling diurnal variation in leaf extension, pot-grown Salix viminalis L.
      were supplied with nitrogen at a low relative addition rate of 0.05 g N g(-1) N
      day(-1) (low N) or were given free access to all nutrients (high N). Leaf
      extension, turgor pressure, turgor after stress relaxation and the plastic
      extensibility of leaf tissue were determined for growing leaves every 4 h during
      two days of clear skies in August. Plants in the high-N treatment had a
      significantly higher relative growth rate, dry weight, shoot/root ratio, leaf
      nitrogen concentration, total leaf area, final area of single leaves and
      epidermal cell size than plants in the low-N treatment. The periodicity of leaf
      extension was similar in both treatments with high values during the afternoon
      and early evening, and negligible values during the night and in the early
      morning. The maximum rate of leaf extension was higher in high-N than in low-N
      plants. Leaf water potential and leaf osmotic potential decreased in the morning
      and increased in the afternoon with highest values during the night. Calculated
      values of turgor pressure showed no consistent diurnal trend and did not
      correlate with the rate of leaf extension. There was no consistent difference in
      turgor between treatments. Turgor after stress relaxation varied diurnally. The
      difference between turgors before and after stress relaxation also varied
      diurnally and was largely in phase with the diurnal pattern of leaf extension.
      These data are consistent with either a causal role for growth turgor (difference
      between turgors before and after stress relaxation) in the regulation of cell
      expansion, or a diurnal variation in turgors after relaxation, attributable to
      different capacities for cell wall loosening at different times of day. Plastic
      extensibility of leaf tissue showed no diurnal pattern but consistently higher
      values were found in high-N than in low-N plants. We conclude that the effects of
      nitrogen supply on leaf water relations did not limit leaf extension, but that
      nitrogen supply did affect processes associated with cell wall loosening and
      enlargement. Nitrogen supply did not affect final values of turgor after
      relaxation, but it presumably affected the rate at which relaxation proceeded.

PMID- 14967624
TI  - Structural scaling of light interception efficiency in Picea engelmannii and
      Abies lasiocarpa.
AB  - Sunlight interception efficiency was compared at the leaf, shoot, branch and
      crown levels for Picea engelmannii (Parry) and Abies lasiocarpa ((Hook.) Nutt.),
      dominant tree species of the central Rocky Mountains, USA. The ratio of
      silhouette to total leaf area (STAR) was used to quantify the efficiency of
      direct-beam sunlight interception at each structural scale. Total mean reductions
      in STAR from the leaf to the crown level were 0.39 to 0.06 in P. engelmannii and
      0.46 to 0.02 in A. lasiocarpa. These reductions in STAR occurred for both species
      as structural scale increased due to a more upright leaf inclination, increased
      leaf twisting and curvature, or greater mutual shading among plant structures. A
      steeper leaf inclination between the leaf and shoot level accounted for 26 +/-
      19% (95% C.I.) of the total leaf-to-crown STAR reduction; mutual shading among
      leaves on shoots caused a 14 +/- 7% reduction, whereas leaf curvature and
      twisting accounted for 22 +/- 3% for a total reduction of 62 +/- 8%. The STAR
      varied slightly from the shoot to the branch level (+/- 7%) except for a 26%
      reduction in shade shoots of A. lasiocarpa as a result of increased mutual
      shading among leaves at lateral nodes. Another substantial reduction in STAR
      occurred from the branch to the crown level (35 +/- 3% of total) as a result of
      shading of one branch layer by another within the crown. Thus, light interception
      efficiency decreased as structural scale increased in both species, especially
      from the leaf to the shoot level and from the branch to the crown level.

PMID- 14967625
TI  - Root produced DHZR-, ZR- and IPA-like cytokinins in xylem sap in relation to
      coppice shoot initiation and growth in cloned trees of Betula pubescens.
AB  - Six-year-old cloned Betula pubescens Ehrh. trees, grown outdoors at 65 degrees
      01' N, were cut on six dates during the growing season to study coppice shoot
      development in relation to root-produced cytokinin-like compounds. Bleeding sap
      was collected over timed intervals for two days after cutting, and endogenous
      cytokinin-like compounds were measured by ELISA assay in HPLC-purified fractions
      of xylem sap. Initiation and development of coppice shoots on the clonally
      propagated plants were comparable to those in seedlings. Coppice shoot initiation
      was affected by the time of cutting, diminishing significantly after June. Of the
      cytokinin-like compounds detected in the xylem sap, zeatin riboside-like (ZR)
      compounds were present in the highest concentrations, and the concentrations of
      dihydrozeatin riboside-like (DHZR) and isopentenyladenoside-like (IPA) compounds
      were approximately one third and one eighth of the ZR concentrations,
      respectively. The concentration of cytokinin-like compounds was positively
      correlated with xylem sap flow rate. The export of cytokinin-like compounds,
      especially DHZR- and ZR-types, was positively correlated with the initiation and
      elongation rate of coppice shoots, the number of lateral branches, and the radial
      growth of the more slowly growing coppice shoots. The export of cytokinin-like
      compounds collected immediately after cutting may represent the basal value for
      each tree. This value is probably affected by the size and activity of the root
      system and may be a relevant estimate for predicting the success of coppicing.

PMID- 14967626
TI  - 14C Allocation in tree-soil systems.
AB  - We studied whole-tree C allocation with special emphasis on the quantification of
      C allocation to roots and root respiration. To document seasonal patterns of C
      allocation, 2-year-old hybrid poplar trees greater than 3 m tall were labeled
      with (14)CO(2) in a large Plexiglas chamber in the field, in July and September.
      Climate and CO(2) concentration were controlled to track ambient conditions
      during labeling. Individual tree canopy CO(2) assimilation averaged 3.8 micromol
      CO(2) m(-2) s(-1) (12.9 g C day(-1) tree(-1)) in July and 6.2 micromol CO(2) m(
      2) s(-1) (9.8 g C day(-1) tree(-1)) in September. Aboveground dark respiration
      was 12% of net daytime C fixation in July and 15% in September. Specific activity
      of root-soil respiration peaked 2 days after labeling and stabilized to less than
      5% of maximum 2 weeks later. Low specific activity of root-soil respiration and a
      labeled pool of root C demonstrated that current photosynthate was the primary
      source of C for root growth and maintenance during the growing season. Root
      respiration averaged 20% of total soil respiration in both July and September
      based on the proportion of labeled C respired to labeled C fixed. In July, 80% of
      the recovered (14)C was found above ground and closely resembled the weight
      distribution of the growing shoot. By September, 51% of the recovered (14)C was
      in the root system and closely resembled the weight distribution of different
      size classes of roots. The finding that the distribution of biomass and (14)C
      were similar verified that the C introduced during labeling followed normal
      seasonal translocation pathways. Results are compared to smaller scale labeling
      studies and the suitability of the approach for studying long-term C fluxes is
      discussed.

PMID- 14967627
TI  - Effects of soil water deficit on gas exchange characteristics and water relations
      of orchard lychee (Litchi chinensis Sonn.) trees.
AB  - Eight-year-old lychee (Litchi chinensis Sonn.) trees, cv. 'Bengal,' growing in
      krasnozem soil were subjected to soil water deficit from one month before
      flowering until harvest by covering the ground with polyethylene sheeting and
      withholding irrigation. The ratio of daytime stomatal conductance of unirrigated
      to irrigated trees decreased 20% during the three months of increasing water
      deficit. Predawn leaf water potentials of irrigated trees averaged about -0.3 MPa
      throughout the period, whereas they declined progressively to -0.9 MPa in
      unirrigated trees. Minimum daytime leaf water potential in the unirrigated trees
      decreased from -1.0 to -1.1 MPa at the beginning of the drought period to -2.2 to
      -2.4 MPa after three months, and calculated whole-plant conductance did not
      change with decreasing availability of water. The calculated soil-root water
      potential declined to less than -1.0 MPa in unirrigated trees. Capacitance
      effects on the relationship between leaf water potential and transpiration were
      significant only at low transpiration rates. Although unirrigated trees reduced
      soil water content at 0-30 cm depths to an equivalent water potential of -1.0
      MPa, fruit shedding was significantly less than in irrigated trees. Water deficit
      had no effect on the fresh weight of pericarp, but caused increased seed size and
      decreased fresh weight of flesh, resulting in fruit from unirrigated trees being
      16% lower in total fresh weight per fruit than fruit from irrigated trees.

PMID- 14967628
TI  - Effects of manganese deficiency on soluble apoplastic peroxidase activities and
      lignin content in needles of Norway spruce (Picea abies).
AB  - Apoplastic peroxidase activities were investigated in manganese-deficient and
      manganese-sufficient needles of field-grown Norway spruce trees (Picea abies L.).
      In Mn-sufficient needles, two sets of peroxidases, one with an alkaline pI >/= 9
      and another with an acidic pI </= 3, were identified using guaiacol or
      coniferylalcohol as substrates for activity staining after isoelectric focusing
      in a pH gradient from 3 to 9. The acidic peroxidases were capable of Mn-dependent
      NADH oxidation and H(2)O(2) formation. Syringaldazine peroxidase activity was not
      found in apoplastic extracts, but was present in whole-needle extracts. Manganese
      deficiency did not affect the activity or the isoelectric focusing pattern (pH 3
      to 9) of the apoplastic peroxidases. Soluble peroxidase activities from whole
      needle extracts were significantly higher in Mn-deficient than in Mn-sufficient
      needles with all substrates tested. Mn-deficient needles contained slightly less
      cell wall material than Mn-sufficient needles, but the lignin content was
      similar. Neither apoplastic peroxidase activity nor lignification was affected by
      Mn deficiency, suggesting that apoplastic peroxidases are regulated independently
      from symplastic peroxidases.

PMID- 14967629
TI  - Induction and stability of somaclonal variation in growth, leaf phenotype and gas
      exchange characteristics of poplar regenerated from callus culture.
AB  - Populus trichocarpa Torr. and Grey x P. balsamifera L. TT32 lines were
      regenerated from calli that had been maintained under differing in vitro
      conditions for sixteen months. In the final months, calli were maintained with
      one of six concentrations of 2,4-dichlorophenoxyacetic acid (2,4-D, 0.1, 0.2,
      0.3, 0.4, 0.5 or 0.6 mg l(-1))and regenerated with 0.25, 0.50 or 1.0 mg l(-1)
      benzylaminopurine (BA). Regenerant lines were obtained from 15 of these 18
      treatments. The spectrum of variation in several morphological, physiological and
      leaf gas exchange traits was evaluated in the primary regenerants in 1986, and in
      their secondary vegetative propagules in the two subsequent years, in relation to
      differences in the original culture conditions. The results indicate that
      somoclonal variation was induced largely as a result of prolonged culture in the
      presence of 2,4-D, but that the terminal maintenance and regeneration phases also
      induced changes in the regenerants. Qualitative differences among the regenerant
      lines were detected by the end of 1986. For most traits, these differences were
      statistically confirmed within the 3-year period. The treatment lines ultimately
      diverged sufficiently to produce lines showing general performance that was
      either above or below that of the original TT32 clone. An early visible indicator
      of this divergence was variation in leaf shape (leaf length/width ratio), which
      could be related to 2,4-D-BA interactions in the final stages of culture. Graphic
      illustration of the independent effects of either 2,4-D or BA on stem height and
      gas exchange parameters suggested an inverse relationship with BA concentration
      and a complex interaction with 2,4-D. Significant correlations were detected
      between gas exchange parameters and morphological characteristics representing
      leaf form and stem development. Overall, the results indicate the presence of
      somaclonal lines that offer potential for the selective improvement of growth
      using morphological and gas exchange parameters as screening tools.

PMID- 14967630
TI  - Somaclonal variation in growth, leaf phenotype and gas exchange characteristics
      of poplar: utilization of leaf morphotype analysis as a basis for selection.
AB  - Populus hybrid TT32 lines produced from 15 treatment tissue culture regimes
      exhibited somaclonal variation in morphological and gas exchange parameters.
      Within four years of regeneration, discrete lines showing statistically validated
      superior, or inferior, growth performance relative to the parental reference
      clone were identified. Significant differences in the ratio of leaf length/width
      between treatment lines provided the earliest reliable indicator of the
      divergence in overall growth performance. Despite discernible variation in leaf
      phenotype among primary regenerants and secondary propagules within individual
      lines, the leaf length/width ratio was identified as a potential parameter for
      predicting growth performance. Its subsequent use led to the recognition of four
      distinct leaf morphotypes; cordate, ovate, reniform and oval. Two or more of
      these morphotypes were distributed within each of the original 15 treatment
      lines. Regrouping the data on the basis of leaf morphotype resulted in a clear
      segregation of the morphological traits, and revealed differences that were not
      readily apparent by statistical analysis based on treatment groups. The
      demonstration of similar relative performances by individual morphotypes with
      respect to a range of growth and gas exchange parameters confirmed that variation
      in leaf morphology was indicative of differential photosynthetic performance.
      Somaclonal variants with a leaf morphology was indicative of differential
      photosynthetic performance. Somaclonal variants with a leaf morphotype closest to
      that of the parental line showed the highest overall potential for selection,
      suggesting that the greatest benefits accrue from a minimal disturbance of the
      parental leaf phenotype.

PMID- 14967631
TI  - Enhancement of the endogenous cytokinin concentration in poplar by transformation
      with Agrobacterium T-DNA gene ipt.
AB  - The agrobacterial isopentenyltransferase (ipt) gene, under the control of its
      native promoter, was transferred to poplar (Populus tremula x P. alba) by an
      Agrobacterium co-cultivation method. The ipt-transformed stem explants developed
      calli that regenerated many buds in the absence of exogenous cytokinins.
      Microcuttings of the ipt transformants exhibited frequently branching shoots with
      short internodes that were unable to root. In this material, the concentrations
      of zeatin, zeatin riboside and isopentenyladenosine, determined by an indirect
      enzyme-linked immunosorbent assay (ELISA), were 4.8-. 17.1- and 14.6-fold higher,
      respectively, than in non-transformed shoots. Results are discussed with regard
      to cytokinin metabolism.

PMID- 14967632
TI  - Carbohydrate requirements for dark respiration by peach vegetative organs.
AB  - The specific respiration rate at 20 degrees C (R(20)) of peach leaves and stems
      declined rapidly from a high value in the early spring (22.5 nmol CO(2) g(dw) (
      1) s(-1)) to relatively constant rates by July (3.1 nmol CO(2) g(dw) (-1) s(-1)).
      Leaf R(20) declined more rapidly than current-year stem R(20), but leaf and
      current-year stem R(20)s were similar by July. The R(20) of current-year stems in
      July was approximately 2.5 times greater than that of one-year-old stems (1.3
      nmol CO(2) g(dw) (-1) s(-1)), and about 30 times greater than that of the trunk
      R(20) (0.1 nmol CO(2) g(dw) (-1) s(-1)). The Q(10)s of leaves and stems were
      approximately 2 for a temperature increase between 20 and 30. The Q(10)s above 30
      were 2.03 for leaves but only 1.61 for stems. Leaves and current-year stems
      accounted for 2 and 17% of the aboveground vegetative biomass in April and
      August, respectively, but accounted for 59-80% of total daily (24 h) respiration.
      Although trunk biomass accounted for 91 and 77% of aboveground vegetative
      biomass, in April and August, respectively, trunk respiration accounted for only
      8-15% of daily aboveground respiration. Before harvest, during a period when
      fruit growth was source-limited, daily fruit respiration exceeded respiration by
      all aboveground vegetative organs.

PMID- 14967633
TI  - Shape of tree stems-a re-examination of the uniform stress hypothesis.
AB  - The transfer matrix method of structural analysis was used to examine the
      hypothesis that tree stems grow to a shape that tends to equalize the average
      bending plus axial stresses to which they are subjected along their length. The
      method and computational procedures were checked by comparing computed height
      diameter profiles with those calculated using elementary stress theory for trees
      with simple force distributions in the crown. Measured height-diameter profiles
      for trees were then taken from the literature and shown to be well-fitted by
      profiles calculated to give uniform stress along the stems, using the most
      realistic average forces and force distributions within the crowns. At high wind
      speeds, the height-diameter profile giving uniform stress was more tapered than
      the profile giving uniform stress at low wind speeds. The profile giving uniform
      stress was similar over the normal range of average wind speeds of 2.5 to 10.0 m
      s(-1) (at the top of the canopy). But a tree that had grown to give uniform
      stress along its stem in an average wind of 5 m s(-1) showed markedly decreased
      stress with height at wind speeds of about 15 m s(-1) or more, and increased
      stress with height (to the crown base) at wind speeds of about 1.25 m s(-1) or
      less. The fact that tree stems develop shapes in response to average conditions,
      but show varying stress distribution in extreme conditions, may help to explain
      some of the apparent evidence for non-uniform stress distribution in the
      literature. In general, our analysis supports the above hypothesis for the stem
      region above the butt swell.

PMID- 14967634
TI  - Uptake and distribution of calcium and phosphorus in beech (Fagus sylvatica) as
      influenced by aluminum and nitrogen.
AB  - We studied the effects of excess nitrogen added as nitrate (NO(3) (-)) or
      ammonium (NH(4) (+)), or both, on mineral nutrition and growth of beech (Fagus
      sylvatica L.) plants grown at pH 4.2 in Al-free nutrient solution or in solutions
      containing 0.1 or 1.0 mM AlCl(3). A high external concentration of NH(4) (+)
      increased the concentration of nitrogen in roots, stems and leaves. The
      root/shoot dry weight ratio was less in plants grown in the presence of NH(4) (+)
      than in plants grown in the presence of NO(3) (-). The concentration of
      phosphorus in the roots was increased and the concentration of potassium in all
      parts of the plant was decreased by NH(4) (+). A high external concentration of
      NO(3) (-) caused a decrease in phosphorus concentrations of the root, stem and
      leaf. Uptake of (45)Ca(2+) by roots was reduced in the presence of high
      concentrations of NH(4) (+) or NO(3) (-), and a combination of high
      concentrations of nitrogen and aluminum further reduced the uptake of (45)Ca(2+).
      Uptake of phosphate ((32)P) and concentrations of phosphorus in root and shoot
      were increased when plants were grown in the presence of 0.1 mM Al. Exposure to
      1.0 mM Al, however, reduced the concentration of phosphorus in roots and shoots
      and the reduction was greater when plants were grown in the presence of a high
      external NO(3) (-) concentration. Aluminum binds to roots, and plants grown in
      the presence of 1.0 mM Al had a slightly higher concentration of aluminum in
      roots than plants grown in the presence of 0.1 mM Al, whereas the concentration
      of Al in the shoot was increased 2 to 3 times in plants exposed to 1.0 mm Al.
      Furthermore, the effects of 1.0 mM Al on uptake of other macronutrients were
      quite different from the effects of 0.1 mM Al. We conclude that 0.1 mM Al
      facilitates uptake and transport of phosphorus in beech and that between 0.1 and
      1.0 mM Al there is a dramatic change in the effects of Al on uptake and transport
      of divalent cations and phosphorus.

PMID- 14967635
TI  - Relationships between nutrient supply, nitrogen partitioning and growth in young
      Sitka spruce (Picea sitchensis).
AB  - Budget studies have shown that internal cycling may contribute a large proportion
      of the annual nutrient supply required to support new growth in trees. Use of
      budgets to quantify internal cycling only quantifies the net transfer of
      nutrients within the plant. Differential partitioning of remobilized nutrients
      and current nutrient uptake could lead to errors in the interpretation of results
      from these studies. We have quantified the dynamic relationships among tree
      growth, nutrient uptake and internal cycling by labeling the current uptake of N
      in trees that received contrasting amounts of nutrient. Two-year-old seedlings of
      Sitka spruce (Picea sitchensis (Bong.) Carr.) were grown in sand culture in a
      greenhouse for one year. The trees received nutrients in a balanced solution at
      either a high (high-RAR) or a low (low-RAR) relative addition rate throughout the
      experiment. Current N uptake was labeled with (15)N from April 13 to July 25.
      Thereafter, trees were re-potted in clean sand and unlabeled N applied until
      November 13. Overall growth was sustained for approximately 10 weeks before
      treatment effects were observed. Initially, no differences in the partition of
      growth or remobilized N occurred, although partition of current uptake favored
      the roots of plants in the low-RAR treatment. After 6 weeks, the partition of
      both growth and remobilized N altered in favor of roots of plants in the low-RAR
      treatment. Nutrient supply had no effect on the amount or rate of N
      remobilization. No evidence was found to suggest that N taken up in the current
      season and partitioned to preexisting shoots or roots is remobilized late in the
      season to support growth of new shoots. However, some trees in the high-RAR
      treatment exhibited a second flush of growth later in the season that was
      partially sustained by remobilization of (15)N from current shoots formed earlier
      in the season. Use of (15)N demonstrated differential partitioning of current
      uptake and remobilized N. The results highlight the limitations of simple budget
      studies for quantifying internal cycling.

PMID- 14967636
TI  - Crown architecture of understory and open-grown white pine (Pinus strobus L.)
      saplings.
AB  - Crown architecture and growth allocation were studied in saplings of eastern
      white pine (Pinus strobus L.), a species classified as intermediate in shade
      tolerance. A comparison was made of 15 understory saplings and 15 open-grown
      saplings that were selected to have comparable heights (mean of 211 cm, range of
      180-250 cm). Mean ages of understory and open-grown trees were 25 and 8 years,
      respectively. Understory trees had a lower degree of apical control, shorter
      crown length, and more horizontal branch angle, resulting in a broader crown
      shape than that of open-grown trees. Total leaf area was greater in open-grown
      saplings than in understory saplings, but the ratio of whole-crown silhouette
      (projected) leaf area to total leaf area was significantly greater in understory
      pine (0.154) than in open-grown pine (0.128), indicating that the crown and shoot
      structure of understory trees exposed a greater percentage of leaf area to direct
      overhead light. Current-year production of understory white pine was
      significantly less than that of open-grown white pine, but a higher percentage of
      current-year production was allocated to foliage in shoots of understory
      saplings. These modifications in crown structure and allocation between open
      grown and understory white pine saplings are similar to those reported for more
      shade-tolerant fir (Abies) and spruce (Picea) species, but the modifications were
      generally smaller in white pine. As a result, white pine did not develop the flat
      topped "umbrella" crown structure observed in understory fir and spruce, which
      approaches the idealized monolayer form that maximizes light interception. The
      overall change to a broader crown shape in understory white pine was
      qualitatively similar, but much more limited than the changes that occurred in
      fir and spruce. This may prevent white pine from persisting in understory shade
      as long as fir and spruce saplings.

PMID- 14967637
TI  - Heat-shock response of Pinus and Picea seedlings.
AB  - The effect of a short period of elevated temperature, or heat shock, on protein
      synthesis was investigated in 2-day-old seedlings of jack pine (Pinus banksiana
      Lamb.), loblolly pine (P. taeda L.), lodgepole pine (P. contorta Dougl.), black
      spruce (Picea mariana (Mill.) BSP), and white spruce (P. glauca (Moench) Voss.).
      In all species, heat shock led to increased [(35)S]methionine incorporation into
      heat-shock proteins (hsp's) with molecular masses of 83 and 72 kDA. Heat shock
      also induced synthesis of several low molecular weight proteins that were absent
      from control seedlings. The low molecular weight hsp's produced by pine seedlings
      had molecular masses of 27, 24.6, 20.5 and 17.5 kDa, whereas those produced by
      spruce seedlings had molecular masses of 27.2, 19.8, 18.4, 17.2 and 16.0 kDa. All
      of the low molecular weight hsp's showed isoelectric variants. Heat shock led to
      increased [(35)S]methionine incorporation into a group of low molecular weight
      hsp's that were also present in control seedlings.

PMID- 14967638
TI  - Changes in gas exchange characteristics during the life span of giant sequoia:
      implications for response to current and future concentrations of atmospheric
      ozone.
AB  - Native stands of giant sequoia (Sequoiadendron giganteum Bucholz) are being
      exposed to relatively high concentrations of atmospheric ozone produced in urban
      and agricultural areas upwind. The expected change in environmental conditions
      over the next 100 years is likely to be unprecedented in the life span (about
      2,500 years) of giant sequoia. We determined changes in physiological responses
      of three age classes of giant sequoia (current-year, 12-, and 125-year-old) to
      differing concentrations of ozone, and assessed age-related differences in
      sensitivity to pollutants by examining physiological changes (gas exchange, water
      use efficiency) across the life span of giant sequoia (current-year, 2-, 5-, 20-,
      125-, and > 2,000-year-old trees). The CO(2) exchange rate (CER) was greater in
      current-year (12.1 micro mol CO(2) m(-2) s(-1)) and 2-year-old seedlings (4.8
      micro mol CO(2) m(-2) s(-1)) than in all older trees (3.0 micro mol CO(2) m(-2)
      s(-1), averaged across the four older age classes). Dark respiration was highest
      for current-year seedlings (-6.5 +/- 0.7 micro mol CO(2) m(-2) s(-1)) and was
      increased twofold in symptomatic individuals exposed to elevated ozone
      concentrations. Stomatal conductance (g(s)) was greater in current-year (355 mmol
      H(2)O m(-2) s(-1)) and 2-year-old seedlings (200 mmol H(2)O m(-2) s(-1)) than in
      all older trees (50 mmol H(2)O m(-2) s(-1)), indicating that the ozone
      concentration in substomatal cavities is higher in young seedlings than in trees.
      Significant changes in water use efficiency, as indicated by C(i)/C(a), occurred
      in trees between ages 5 and 20 years. We conclude that giant sequoias seedlings
      are sensitive to atmospheric ozone until they are about 5 years old. Low
      conductance, high water use efficiency, and compact mesophyll all contribute to a
      natural ozone tolerance, or defense, or both, in foliage of older trees.

PMID- 14967639
TI  - Offsetting changes in biomass allocation and photosynthesis in ponderosa pine
      (Pinus ponderosa) in response to climate change.
AB  - We examined the effect of climate on aboveground biomass allocation of ponderosa
      pine (Pinus ponderosa) by measuring trees in disjunct forest stands growing on
      the same substrate at high-elevation montane sites and low-elevation desert
      sites. Climatic differences between the sites were comparable to the difference
      between present and future climates of interior North America that is expected to
      result from a doubling of atmospheric CO(2) concentration. Relative to the
      montane populations, the desert populations allocated a greater proportion of
      biomass to sapwood (functional xylem) at the expense of foliage. The leaf/sapwood
      area ratio and percent of aboveground biomass in sapwood for trees of the same
      height were 0.201 m(2) cm(-2) and 58% for montane trees and 0.104 m(2) cm(-2) and
      71% for desert trees. In a phytotron experiment, increases in net photosynthesis
      and net assimilation rate for seedlings grown under future conditions of high
      CO(2) and temperature were offset by a decrease in leaf area ratio. As was
      observed for large trees at different elevations, increased temperatures caused
      an increase in biomass allocation to stem in the phytotron seedlings. Thus, CO(2)
      and temperature-driven shifts in biomass allocation negated the effect on growth
      of the CO(2)-driven increase in carbon assimilation rate. Our data from the
      controlled growth chamber and field experiments suggest that future climate
      conditions, including elevated atmospheric CO(2), may not stimulate growth and
      productivity of ponderosa pine.

PMID- 14967640
TI  - Interactive effects of elevated CO(2) and mineral nutrition on growth and CO(2)
      exchange of sweet chestnut seedlings (Castanea sativa).
AB  - The effects of elevated atmospheric CO(2) (700 micro mol mol(-1)) and
      fertilization were investigated on 2-year-old sweet chestnut (Castanea sativa
      Mill.) seedlings grown outdoors in pots in constantly ventilated open-sided
      chambers. Plants were divided into four groups: fertilized controls (+F/-CO(2)),
      unfertilized controls (-F/-CO(2)), fertilized + CO(2)-treated plants (+F/+CO(2))
      and unfertilized + CO(2)-treated plants (-F/+CO(2)). Dry matter accumulation and
      allocation were measured after one growing season and CO(2) exchange of whole
      shoots was measured throughout the growing season. Shoot growth and total leaf
      area of unfertilized plants were not affected by elevated CO(2), whereas both
      parameters were enhanced by elevated CO(2) in fertilized plants. Elevated CO(2)
      increased total biomass by about 20% in both fertilized and unfertilized plants;
      however, biomass partitioning differed. In unfertilized plants, elevated CO(2)
      caused an increase in root growth, whereas in fertilized plants, it stimulated
      aboveground growth. At the whole-shoot and leaf levels, photosynthetic activity
      of both fertilized and unfertilized plants increased in response to elevated
      CO(2), but the seasonal pattern of this enhancement varied with nutrient
      treatment. In unfertilized plants, a downward acclimation of photosynthesis was
      observed early in the season (June), and was related to reductions in nitrogen
      and chlorophyll content and to starch accumulation. The decrease in the slope of
      the A/C(i) curve suggested a decrease in Rubisco activity. In both fertilized and
      unfertilized plants, shoot respiration decreased during the night in response to
      elevated CO(2) until mid-July. The decrease was not related to changes in sugar
      concentration.

PMID- 14967641
TI  - Effects of elevated CO(2), nutrition and climatic warming on bud phenology in
      Sitka spruce (Picea sitchensis) and their impact on the risk of frost damage.
AB  - Effects of elevated CO(2), clone and plant nutrition on bud dormancy of Sitka
      spruce (Picea sitchensis (Bong.) Carr.) were examined. Sitka spruce seedlings
      were fumigated with ambient or elevated (ambient + 350 micro mol mol(-1))
      concentrations of CO(2) in open-top chambers for three growing seasons. In 1991
      and 1992, elevated CO(2) delayed bud burst in the spring and advanced bud set in
      the autumn. The effect of the open-top chamber on the thermal requirement for bud
      burst was greater than the effect of elevated CO(2) (50 and 30 day degrees
      (D(d)), respectively). In a second study, four clones of Sitka spruce taken from
      two provenances, at 43 and 54 degrees N, were fumigated with ambient or elevated
      CO(2). There was a large natural variation in the timing of bud burst and bud set
      among the clones. Elevated CO(2) had no effect on bud dormancy of the Skidegate a
      clone, but it reduced the growing season of the North Bend b clone by 20 days. In
      a third study, Sitka spruce seedlings growing in ambient or elevated CO(2), were
      supplied with one of three nutrient regimes, low (0.1 x potential), medium (0.5 x
      potential) or high (2.0 x potential), using a method and solution based on the
      Ingestad technique. Elevated CO(2) did not affect bud dormancy in the high
      nutrient treatment, but it reduced the growing season of plants in the low
      nutrient treatment by 22 days. Increasing plant nutrient supply lengthened the
      growing season, plants flushed earlier in the spring and set bud later in the
      autumn. The effects of elevated CO(2) plus a 0, 2 or 4 degrees C climatic warming
      on the timing of bud burst and the subsequent risk of frost damage were assessed
      using a simulation model and meteorological data from three sites, Edinburgh,
      Braemar and Masset. The model predicted that (i) doubling the CO(2) concentration
      in the absence of climatic warming, will delay the onset of bud burst at all
      three sites, (ii) climatic warming in ambient CO(2) will hasten bud burst and
      (iii) climatic warming in elevated CO(2) will hasten bud burst at Edinburgh and
      Braemar but to a lesser extent than climatic warming alone. At Masset, a 4
      degrees C warming was required to advance the date of bud burst of seedlings in
      the elevated CO(2) treatment. At all three sites, elevated CO(2) and climatic
      warming increased the mean daily temperature on the date of bud burst, thus
      reducing the risk of subsequent frost damage.

PMID- 14967642
TI  - Interactive effects of elevated CO(2) and soil drought on growth and
      transpiration efficiency and its determinants in two European forest tree
      species.
AB  - The responses of growth and transpiration efficiency (W = biomass
      accumulation/water consumption) to ambient and elevated atmospheric CO(2)
      concentrations (350 and 700 micro mol mol(-1), respectively) were investigated
      under optimal nutrient supply in well-watered and in drought conditions in two
      temperate-forest tree species: Quercus petraea Liebl. and Pinus pinaster Ait.
      Under well-watered conditions, doubling the CO(2) concentration for one growing
      season increased biomass growth by 138% in Q. petraea and by 63% in P. pinaster.
      In contrast, under drought conditions, elevated CO(2) increased biomass growth by
      only 47% in Q. petraea and had no significant effect on biomass growth in P.
      pinaster. Transpiration efficiency was higher in Q. petraea than in P. pinaster
      in all treatments. This difference was linked (i) to lower carbon isotope
      discrimination (Delta), and thus lower values of the intercellular/ambient CO(2)
      concentration (c(i)/c(a)) ratio, in Q. petraea, (ii) to lower values of leaf mass
      ratio (LMR, leaf mass/whole plant mass), which we suggest was positively related
      to the proportion of daytime carbon fixation lost by respiration (Phi), in Q.
      petraea, and (iii) to slightly lower C concentrations in Q. petraea than in P.
      pinaster. The CO(2)-promoted increase in W was higher in Q. petraea (+80%) than
      in P. pinaster (+50%), and the difference was associated with a more pronounced
      decrease in Phi in response to elevated CO(2) in Q. petraea than in P. pinaster,
      which could be linked with the N dilution effect observed in Q. petraea. Because
      Phi also directly affects growth, the CO(2)-induced enhancement of Phi in Q.
      petraea is a crucial determinant of the growth stimulation observed in this
      species. Leaf gas exchange regulation was not the only factor involved in the
      responses of growth and W to elevated CO(2) and drought, other physiological
      processes that have crucial roles include carbon and N allocation and
      respiration.

PMID- 14967643
TI  - Relationship between CO(2)-dependent O(2) evolution and photosystem II activity
      in oak (Quercus petraea) trees grown in the field and in seedlings grown in
      ambient or elevated CO(2).
AB  - The light-response of the apparent quantum yield of photosynthetic O(2) evolution
      (Phi(O(2) )) under non-photorespiratory conditions was measured together with the
      photochemical efficiency of PS II (DeltaF/F(m)'), the photochemical efficiency of
      open PS II reaction centers (F(v)'/F(m)') and the photochemical fluorescence
      quenching (q(p)) of leaf disks punched from oak leaves of seedlings grown in
      ambient (350 micro mol mol(-1)) or elevated (700 micro mol mol(-1)) CO(2) in a
      greenhouse, and from sunlit leaves of mature oak trees (Quercus petraea (Matt.)
      Liebl.). There were marked differences between seedlings and trees. In seedlings,
      CO(2) concentration during growth did not modify the light response of
      photosynthesis or PS II activity. There was a single linear relationship between
      Phi(O(2) ) and DeltaF/F(m)' in seedling leaves that was independent of the CO(2)
      concentration imposed during growth. In contrast, this relationship was
      curvilinear in sunlit leaves of adult trees. In seedling leaves, the decrease in
      q(p) (i.e., the proportion of open PS II reaction centers) largely accounted for
      the decrease in DeltaF/F(m)', whereas the decrease in DeltaF/F(m)' in sunlit
      leaves of mature oak trees was dependent on both q(p) and F(v)'/F(m)'.

PMID- 14967644
TI  - Shade, leaf growth and crown development of Quercus rubra, Quercus velutina,
      Prunus serotina and Acer rubrum seedlings.
AB  - The study was conducted in an open field to determine the optimum irradiance for
      establishment and growth of two oak species and two major associated woody
      species. Half-sib seedlings of black cherry (Prunus serotina Ehrh.), red maple
      (Acer rubrum L.), northern red oak (Quercus rubra L.) and black oak (Q. velutina
      Lam.) were grown for two years under shade-cloth tents. Eight shade treatments
      (94, 70, 57, 45, 37, 27, 20 and 8% of full sunlight) with three replications each
      were used. Measurements were made on seedlings harvested at the end of the first
      and second growing seasons. In the second year, shading significantly decreased
      the number of leaves for all species except black cherry, but only significantly
      decreased leaf area in northern red oak. Shading significantly decreased average
      leaf size of red maple. Average leaf size of black cherry was largest in the
      intermediate shade treatments and decreased significantly with increased and
      decreased shade. Leaf weight/leaf area (mg cm(-2)) increased significantly in a
      quadratic pattern with decreasing shade for all four species. Leaf area ratio
      (cm(2) g(-1)) decreased significantly with decreasing shade for all species
      except red maple in the first year and black oak in the second year. Total branch
      development increased significantly with decreasing shade in red maple and
      northern red oak, whereas indeterminate branches increased significantly with
      decreasing shade only in black cherry, and short branches increased significantly
      with decreasing shade only in red maple.

PMID- 14967645
TI  - Response to light of shade-grown beech seedlings subjected to different watering
      regimes.
AB  - The morphological and physiological responses (net photosynthesis, stomatal
      conductance, leaf chlorophyll concentration and leaf orientation) of shade-grown
      beech seedlings after transfer to a high-light regime were studied in well
      watered plants and in plants subjected to water stress. Immediately after
      exposure to high irradiance, shade-grown seedlings displayed a lower
      photosynthetic rate, a higher leaf chlorophyll concentration and a more
      horizontal leaf orientation than light-acclimated plants (control plants). The
      chlorophyll concentration of shade-grown plants gradually declined throughout the
      period of exposure to high irradiance reaching the amount observed in control
      plants. Rates of photosynthesis of shade-grown plants began to recover after 8
      days of exposure to high irradiance and recovery was nearly complete after 30
      days. Leaf orientation of shade-grown plants also changed rapidly during the
      first 8 days of exposure to high irradiance and by the end of the experiment,
      there were no significant differences between shade-grown and control plants.
      Water stress caused significant declines in net photosynthesis and leaf
      conductance in both shade-grown and control plants. Net photosynthesis did not
      recover completely in the shade-grown water-stressed plants during the 30-day
      exposure to high irradiance. Reversible leaf paraheliotropism and chlorophyll
      bleaching were observed in response to soil drying followed by rewatering.

PMID- 14967646
TI  - A whole-plant cuvette system to measure short-term responses of conifer seedlings
      to environmental change.
AB  - A computer-controlled whole-plant cuvette system is described that allows precise
      and independent control of temperature (+/- 0.05 degrees C), vapor pressure (+/-
      0.02 kPa), CO(2) concentration (+/- 2 micro mol mol(-1)) and photosynthetic
      photon flux density (+/- 5 micro mol m(-2) s(-1)), and allows the continuous
      measurement of net photosynthesis and transpiration rates. Vapor pressure is
      controlled by circulating chamber air through a CaSO(4) desiccant column
      supported on a digital balance. Transpiration rate is calculated from the change
      in desiccant mass with time. Photosynthesis rate is measured by integrating the
      output of a mass flow controller used to inject CO(2) into the chamber to
      compensate for that assimilated by the plant. The control system can be driven by
      set points that can be varied, for example, as a function of time, or held
      constant. We were able to simulate weather data obtained from climate stations
      and accurately follow, in real time, the output of sensors measuring outside
      conditions. Experiments on well-watered one- and two-year-old nursery-raised
      western red cedar (Thuja plicata Donn.) and white spruce (Picea glauca (Moench)
      Voss) seedlings showed that if the mean daily temperature was increased from 20
      to 22 degrees C with vapor pressure remaining constant at 1 kPa, CO(2)
      concentrations must almost double to compensate for the decrease in net
      photosynthesis rate.

PMID- 14967647
TI  - Effects of elevated CO(2) on growth and chloroplast proteins in Prunus avium.
AB  - To predict the future carbon sequestering capacity of trees, we need information
      about the possible acclimatory mechanisms of plant growth and photosynthesis in
      rising atmospheric CO(2) under a variety of environmental conditions. We have,
      therefore, studied the growth response of a tree species (Prunus avium L. Stella
      (wild cherry)) to elevated CO(2) and characterized the associated changes in
      photosynthetic machinery of the leaf tissue. Self-pollinated seedlings and mature
      cuttings (clones) from the same parent plant of P. avium were grown for two
      consecutive growing seasons (about 60 days each) in ambient CO(2) (350 micro mol
      mol(-1) CO(2)) or elevated CO(2) (700 micro mol mol(-1) CO(2)) with a high or low
      nutrient supply. The degree of acclimation of leaf biochemistry and growth
      response to elevated CO(2) was dependent on the plant material (seedling or
      mature cutting) and nutrient supply. There was little or no growth response to
      elevated CO(2) in seedlings or cuttings in the low nutrient supply treatments,
      whereas, in both seasons, there was a strongly positive growth response to
      elevated CO(2) in seedlings and cuttings in the high nutrient supply regimes,
      resulting in increases in the root/shoot ratio and in carbon allocation to the
      roots. In contrast, the protein content and activity of ribulose-1,5-bisphosphate
      carboxylase-oxygenase (Rubisco, EC 4.1.1.39) were down regulated in elevated
      CO(2). The loss of Rubisco on an area basis in plants in the elevated CO(2)
      treatments was compensated for at the canopy level by increased leaf area. The
      loss of Rubisco protein was accompanied by decreases in the contents of
      chlorophyll and the thylakoid membrane proteins D(1), D(2) and cytochrome f,
      which are involved in light harvesting and photo-electron transport. We conclude
      that, in the medium- to long-term, the initial stimulation of biomass production
      by elevated CO(2) may be increasingly offset by a lower photosynthetic capacity
      per unit leaf area in perennial plants.

PMID- 14967648
TI  - The choice of genetic material for mechanistic studies of adaptation in forest
      trees.
AB  - There is considerable urgency to study the mechanisms by which forest trees track
      environmental change, given the prospect of possible rapid climatic changes.
      Environmental tracking is achieved through three basic processes: (1) expression
      of phenotypic plasticity at the level of the individual; and (2) evolutionary
      change and (3) migration, both expressed at the level of the population over
      generations. The current distribution and genetic architecture of a species
      reflect how these processes interacted in response to past climatic changes
      during and after the last glaciation. Part of that record is encoded in the DNA
      of the current generation of trees and, as a result of existing field tests, is
      accessible for study. These field tests include, in ascending order of genetic
      resolution, (1) provenance tests, (2) progeny tests, and (3) three-generation
      clonal tests; as well as (4) clone tests, with or without genetic structure. The
      suitability and limitations of these tests for mechanistic studies of
      environmental tracking are described, both as field installations and as sources
      of material for parallel in-depth studies. We conclude that they represent an
      important information resource, which deserves to be more effectively used by the
      scientific community.

PMID- 14967649
TI  - Modeling climate change effects with provenance test data.
AB  - Provenance tests of forest trees, which were originally intended to identify
      suitable seed sources for planting at different locations, provide valuable data
      for assessing the response of populations to environmental change. Environmental
      differences between the location of origin and the planting (test) site have been
      calculated by principal component analysis and termed ecological distance. Based
      on ecological distance values, the growth response of tree populations can be
      modeled as a function of the test site macroclimate. These models can then be
      used to predict the effects of climatic change on growth and survival. The growth
      response model predicts that increasing annual mean temperatures will result in
      accelerated growth if precipitation is sufficient, but only within the limits
      characteristic of the species. At the southern limits of distribution, growth and
      competitive ability of the species will decline, leading to successional changes.

PMID- 14967650
TI  - Use of provenance tests to predict response to climate change: loblolly pine and
      Norway spruce.
AB  - Provenance tests are often used to determine genetic responses of seed sources to
      transfer to different climates. This study was undertaken to determine whether
      provenance tests can be used to predict tree response to rapid climate changes in
      situ. Data from provenance tests of loblolly pines (Pinus taeda L.), Norway
      spruce (Picea abies L. Karst) and other southern pines (subsect. AUSTRALES Loud.)
      were interpreted using regression models to relate growth to temperature
      variables. Results of different plantings were combined by expressing growth as a
      percent deviation from the "local" source, and expressing temperature at the
      source as a deviation from that of the planting site. The results of the loblolly
      pine and Norway spruce models predicted a loss of about 5 to 10% in height growth
      below that expected for a genetically adapted seed source, if the average yearly
      temperature increases by 4 degrees C.

PMID- 14967651
TI  - Ecotypic differentiation of gas exchange responses and leaf anatomy in a tropical
      forest understory shrub from areas of contrasting rainfall regimes.
AB  - Many studies have documented genetic differentiation of physiological ecotypes
      along environmental gradients in the temperate zone, but this topic has received
      little attention in tropical plants. We collected cuttings of Psychotria
      horizontalis (Rubiaceae) from Atlantic and Pacific coastal areas in central
      Panama, which differed twofold in annual rainfall, and grew them under common
      conditions in a screened, open-air growing house for 14 months. Plants from the
      wetter (Atlantic) region showed significantly higher stomatal conductance, but
      photosynthetic rates were similar in both groups, leading to higher water use
      efficiency in plants from the drier (Pacific) region. Responses of stomatal
      conductance to atmospheric humidity were similar in both groups. Anatomical
      studies show that plants from the wetter region had a higher mesophyll surface
      area per unit leaf area (A(mes)/A(leaf)) than plants from the drier region (17.2
      versus 13.9), and also had a higher stomatal density (161.5 versus 98.0 mm(-2))
      and fewer trichomes (2.0 versus 18.7 mm(-2)). The proportion of palisade cell
      surface area that was exposed to intercellular airspaces is higher in plants from
      the Pacific coast than from the Atlantic coast, such that the total palisade cell
      surface area exposed to the intercellular airspaces is similar in plants from the
      two regions (A(mes)/A(leaf) = 1.7). Paired plants transplanted into natural
      forest understory conditions showed considerable variability among sites, but
      plants from the drier region consistently had lower stomatal conductance than
      plants from the wetter region. After 20 months in the field, plant growth was
      similar regardless of plant origin, but plants of Pacific coast origin had longer
      roots and more (but smaller) leaves than plants of Atlantic coast origin.
      Stomatal density in field-grown plants was higher in plants of Atlantic (135.9
      mm(-2)) than Pacific (90.1 mm(-2)) origin. An understanding of genetically based
      adaptations to local environmental conditions is important for predicting the
      consequences of climatic change and forest fragmentation.

PMID- 14967652
TI  - Genotypic and phenotypic variation as stress adaptations in temperate tree
      species: a review of several case studies.
AB  - Species that occupy large geographic ranges or a variety of habitats within a
      limited area deal with contrasting environmental conditions by genotypic and
      phenotypic variation. My students and I have studied these forms of
      ecophysiological variation in temperate tree species in eastern North America by
      means of a series of field and greenhouse experiments, including controlled
      studies with Cercis canadensis L., Fraxinus pennsylvanica Marsh., Acer rubrum L.,
      Prunus serotina Ehrh. and Quercus rubra L., in relation to drought stress. These
      studies have included measurements of gas exchange, tissue water relations and
      leaf morphology, and have identified genotypic variation at the biome and
      individual community levels. Xeric genotypes generally had higher net
      photosynthesis and leaf conductance and lower osmotic and water potentials at
      incipient wilting than mesic genotypes during drought. Xeric genotypes also
      produced leaves with greater thickness, leaf mass per area and stomatal density
      and smaller area than the mesic genotypes, suggesting general coordination among
      leaf morphology, gas exchange and tissue water relations. Leaf phenotypic
      plasticity to different light environments occurred in virtually every study
      species, which represented a wide array of ecological tolerances. In a study of
      interactions of genotypes with environment, shade plants, but not sun plants,
      exhibited osmotic adjustment during drought and shade plants had smaller
      reductions in photosynthesis with decreasing leaf water potential. In that study,
      sun, but not shade, plants had significant genotypic differences in leaf
      structure, but with certain variables phenotypic variation exceeded genotype
      variation. Thus, genotypic variation was not expressed in all phenotypes, and
      phenotypes responded differentially to stress. Overall, these studies indicate
      the importance of genotypic and phenotypic variation as stress adaptations in
      temperate tree species among both distant and nearby sites of contrasting
      environmental conditions.

PMID- 14967653
TI  - Prospects for increasing the salt tolerance of forest trees: a review.
AB  - Three major themes related to the improvement of salt tolerance in forest tree
      species are examined. First, evidence demonstrating that substantial
      intraspecific variation in salt tolerance exists in many species is presented.
      This evidence is important because it suggests that efforts to improve salt
      tolerance through conventional plant breeding techniques are justified. Second,
      the physiological and genetic mechanisms controlling salt tolerance are discussed
      briefly. Although salt tolerance involves the integration of numerous
      physiological processes, there is considerable evidence that differences in the
      ability to exclude Na(+) and Cl(-) from leaves are the most important factors
      underlying intraspecific differences in tolerance. It is also becoming apparent
      that, although salt tolerance is a multigenic trait, major genes play an
      important role. Third, progress to date in improving salt tolerance of forest
      tree species is assessed. Compared with agricultural crops, relatively little
      progress has been made with either conventional or biotechnological methods, but
      field trials designed to test clones identified as salt tolerant in screening
      trials are underway now in several countries. We conclude that there is
      justification for cautious optimism about the prospects for improving salt
      tolerance in forest tree species.

PMID- 14967654
TI  - Frost injury prediction model for Douglas-fir seedlings in the Pacific Northwest.
AB  - Because simple seed- or breeding-zone guidelines are inadequate for controlling
      the risk of maladaptation to environmental stresses, we are developing
      operational procedures to assess the risk of frost kill to genetically improved
      families of Douglas-fir (Pseudotsuga menziesii Mirb. Franco). We have (1)
      determined the time course of cold hardening and dehardening of nursery-grown
      Douglas-fir seedlings over four winters, by means of controlled freezing tests,
      (2) fitted curves to relationships between temperature sum and both fall cold
      hardening and spring dehardening, (3) applied the temperature sum models to daily
      temperature records of 80 weather stations to estimate frequency of years with
      significant frost kill at those stations, (4) interpolated frost kill
      probabilities for tree farms, using a thin plate spline procedure with elevation,
      latitude and longitude as variables, and (5) prepared a coarse-scale frost risk
      map from the resulting grid point estimates. With the exception of a few high
      elevation stations, the most damaging frost at any station in any year occurred
      in either the fall (October and November) or late spring (mid-April to mid-May).
      In general, damaging spring frosts were two to three times more frequent than
      fall frosts, and areas in Oregon were at greater risk than areas at similar
      elevations and longitudes further north. The spline surface was less precise for
      predicting spring frost risk than fall frost risk.

PMID- 14967655
TI  - Genotypic differences in water use efficiency and (13)C discrimination in
      Eucalyptus globulus.
AB  - Cuttings of three Eucalyptus globulus Labill. clones (called SM, VC, DG
      henceforward) were grown for 56 days in 10-l pots in a greenhouse. Every other
      day, eight pots of each clone were watered to field capacity (HW treatment),
      whereas the other eight pots of each clone received only 25% of the water needed
      to maintain the soil at field capacity (LW treatment). Transpirational water
      loss, biomass production, leaf gas exchange and water potential (at predawn and
      midday) were determined at different times during the experiment. Leaf tissue
      formed by the LW plants after the onset of the treatment was analyzed for
      (13)C/(12)C ratio against the PeeDee Belemnite standard (delta(13)C). The three
      clones differed significantly in growth capacity (SM > DG > VC) and in their
      response to water stress. Even though leaf water potentials were not
      significantly modified by withholding water, total biomass and plant leaf area
      were affected significantly by soil water deficits by the end of the experiment.
      The fastest growing clone (SM) was the most affected by water deficit. Long-term
      water use efficiency (i.e., biomass per unit of water transpired, WUE) was
      significantly increased by water deficit and was positively correlated with
      delta(13)C. Long-term WUE was well correlated with the quotient of the daily
      integrals of carbon assimilation rate and stomatal conductance. The value of
      delta(13)C was negatively correlated with the variables normally positively
      related with growth, such as specific leaf area (SLA) and the biomass/intercepted
      light quotient (epsilon), and it was positively related to the amount of carbon
      per unit leaf area, which is usually negatively correlated with relative growth
      rate.

PMID- 14967656
TI  - Carbon allocation, gas exchange, and needle morphology of Pinus ponderosa
      genotypes known to differ in growth and survival under imposed drought.
AB  - Seedlings from 27 open-pollinated families of ponderosa pine representing nine
      geographically diverse origins were screened for drought tolerance based on
      survival and growth under imposed drought. Seedlings that had been preconditioned
      to drought survived 14 days longer than seedlings that had been well watered
      before being subjected to drought. Seed sources varied in their ability to
      survive drought and this variation was accentuated by drought preconditioning.
      Seedlings from a South Dakota source and a Nebraska source generally survived the
      longest under drought. Seedlings from a Montana source and a New Mexico source
      succumbed the fastest after water was withheld. Significant family within source
      variation in drought survival was observed for some sources. In general, drought
      survival was poorly correlated to climate indices of the seed sources. Allocation
      of biomass to roots, stems, and needles varied significantly among the seed
      sources with the most drought-sensitive sources (Montana and New Mexico) showing
      the most divergent allocation patterns. The relation between drought survival and
      shoot/root ratio suggested that there is an optimum pattern of allocation for
      drought survival. A comparison of the most and least drought-tolerant sources
      indicated that needle gas exchange (net photosynthesis and needle conductance to
      water vapor) and predawn needle water potential were similar among the sources
      regardless of their relative ability to survive drought. Needle morphology traits
      often associated with variation in drought tolerance, such as stomatal density
      and specific leaf area, did not differ among the seed sources. However, seedlings
      from the drought-tolerant sources had shorter needles, less surface area per
      needle, and fewer stomata per needle than seedlings from the drought-sensitive
      sources. The results suggest that drought tolerance of ponderosa pine may be
      improved through seed source selection and, within certain sources, family
      selection. Allocation patterns and needle morphology appear to play a larger role
      than needle gas exchange patterns in determining drought tolerance in this
      species.

PMID- 14967657
TI  - Use of the crown competition factor concept to select clones and spacings for
      short-rotation woody crops.
AB  - Plantation spacing and rotation age are interrelated critical factors in
      optimizing production of short-rotation woody crops (SRWC). Different genotypes
      have different spacing and rotation-age optima. I have developed a method for
      estimating the optimum for new Populus clones based on a modification of the
      crown competition factor (CCF) concept, which was originally developed for
      conventional forestry practices with older trees. Measurements of as few as 100
      trees of a new clone over a relatively short time period could be used to predict
      the optimum spacing and rotation age combinations for that clone. The technique
      could also be used to quantify basic differences in crown architecture and yield
      physiology among genotypes. One set of at least 20 trees is planted at an open
      grown spacing and measured annually for crown and basal stem diameters. The
      regression of crown diameter on stem diameter is used to calculate the land area
      that would be occupied per open-grown tree at various stem diameters. This allows
      prediction of the spacing needed to reach the minimum density for maximum stand
      growth at a given age or stem size. A second set of 80 measurement trees is
      planted in a closely spaced set of Nelder arcs to force overstocking within the
      first few years of growth. Productivity measurements on these trees establish the
      upper limit on CCF for maximum stand growth. The data are then used to calculate
      the best spacing and rotation age combination for a new clone. Application of
      this model may lead to a better understanding of the productive advantages of the
      sylleptic branch habit, different branch angles and seasonal growth rates,
      different carbon allocation strategies, and responses to competition.

PMID- 14967658
TI  - First-order root development from cuttings of Populus trichocarpa x P. deltoides
      hybrids.
AB  - We studied first-order root development of field-grown plants of 44 F(1) Populus
      trichocarpa x P. deltoides hybrids as well as 15 clones of P. trichocarpa (T) and
      20 clones of P. deltoides (D) during their first growing season. The cuttings
      were planted in the field on May 11-12, 1988 and destructively sampled in July,
      August and September. By September 12, hybrids had an average of 50 first-order
      roots per cutting (range = 32 to 85) with an average of 25% dead roots (range =
      10 to 51%). The longest roots of hybrids averaged 107 cm (range = 58 to 182 cm)
      and originated at the base of the cutting. Roots originating at the side of the
      cutting averaged 54 cm in length (range = 12 to 96 cm). For most aboveground and
      root parameters measured, the values for hybrids exceeded those for both parent
      species clones. For all clones, aboveground weights were positively correlated
      with weights of collected roots (R(2) = 0.66 to 0.86). In contrast, aboveground
      weights were negatively (but poorly) correlated with root/shoot ratios (R(2) =
      0.08 to 0.21). Roots differed allometrically depending on their location on the
      cutting. Total weight of roots originating along the sides of the cutting was not
      correlated with aboveground weight (R(2) = 0.001 to 0.27), whereas total weight
      of roots originating at the base of the cutting was correlated with aboveground
      weight (R(2) = 0.52 to 0.80). Basal roots dominated the first-order root systems
      of most clones in terms of maximum length and total mass, but not in total
      numbers of roots.

PMID- 14967659
TI  - Cold acclimation in eucalypt hybrids.
AB  - We evaluated cold resistance and the capacity for cold acclimation of different
      Eucalyptus genotypes. Seedlings of half-sib families of E. globulus and hybrids
      E. gunnii x globulus, E. viminalis x globulus and E. cypellocarpa x globulus were
      exposed daily for 56 days to a 9-h photoperiod at 14.7 degrees C, followed by 15
      h in a dark cold room maintained at 2.5 degrees C with the root system maintained
      at 8 degrees C to cold harden the seedlings. Unhardened seedlings were maintained
      at about 16 degrees C during the dark period. Cold acclimation occurred in all
      families with decreases in the temperature causing 50% mortality (LT(50)) of
      between 1.5 and 3 degrees C. Both hardened and unhardened plants of hybrid
      families were more cold tolerant than E. globulus. A significant correlation
      between LT(50) and leaf osmotic pressure was observed; the increase in osmotic
      pressure in hardened plants was predominantly a result of an increase in the
      concentration of soluble sugars. Exotherm peaks were similar in hardened and
      unhardened plants. These results indicate that cold hardening increased the
      ability of eucalypts to endure extracellular ice formation. The maintenance of
      photosynthetic capacity in cold-hardened plants may also play a role in their
      response to freezing.

PMID- 14967660
TI  - An interregional validation of ECOPHYS, a growth process model of juvenile poplar
      clones.
AB  - Field data from poplar plantations in Michigan, Washington, and Wisconsin were
      used to validate ECOPHYS, a whole-tree growth process model for juvenile poplar.
      Five clones representing a range of morphological, phenological, and
      physiological characteristics were planted on the same date at the three sites.
      Height and diameter measurements were made monthly on 20 trees per clone, and
      intensive morphological measurements were made every two weeks on two trees per
      clone. Hourly solar radiation and temperature data were recorded at each site
      over the growing season. The model was run for each clone x site combination with
      the weather data and clonal parameters as inputs. A repeated measures ANOVA
      indicated that there were significant differences in height growth patterns among
      both clones and sites, as well as significant clone x site interactions. The
      model generally predicted height growth within a standard deviation of the field
      plantation means; three of the 15 clone x site simulations were significantly
      different from the plantation means. The median error between predicted and
      observed values was 5%. Evaluation of the clonal parameters showed that
      differences in photosynthetic rates, morphological attributes such as specific
      leaf area, and timing of budset are primary factors leading to differences in
      growth.

PMID- 14967661
TI  - Effects of leaf nutrient status on photosynthetic capacity in loblolly pine
      (Pinus taeda L.) seedlings grown in elevated atmospheric CO(2).
AB  - We measured needle photosynthesis of loblolly pine seedlings grown in a factorial
      experiment with two CO(2) partial pressures (35 and 65 Pa) and three nutrient
      treatments (7 mM NH(4)NO(3) + 1 mM PO(4); 7 mM NH(4)NO(3) + 0.2 mM PO(4); 1 mM
      NH(4)NO(3) + 1 mM PO(4)). The data were used to parameterize a physiologically
      based photosynthetic model that included limitations imposed by ribulose-1,5
      bisphosphate carboxylase/oxygenase activity, electron transport capacity and
      inorganic phosphate availability. With nonlimiting nutrients, seedlings grown at
      65 Pa CO(2) had significantly higher net photosynthesis and lower stomatal
      conductance than seedlings grown at 35 Pa CO(2). Nutrient limitations by either N
      or P significantly reduced photosynthetic capacity. When either N or P was
      limiting, there was no effect of growth CO(2) partial pressure on photosynthesis,
      but stomatal conductance was significantly lower for seedlings grown at 65 Pa
      CO(2). Modeled biochemical parameters suggest that, in all cases, photosynthesis
      was co-limited by carboxylation, electron transport and phosphate regeneration.
      Acclimation to growth in elevated CO(2) involved a reduction in leaf N content.
      In the low-N and low-P treatments, modeled parameters indicated that the
      biochemical processes of photosynthesis were down regulated to the point that
      there was no effect of increasing CO(2) partial pressure. The capacity to
      regenerate phosphate was reduced in both low nutrient treatments, but was only
      reduced by elevated CO(2) when seedlings were grown under low soil P conditions.
      Increased photosynthetic water use efficiency and nutrient use efficiency in
      response to CO(2) enrichment occurred in all three nutrient treatments and have
      important implications for whole-plant water and nutrient balance. These data
      support the contention that soil nutrient status in forest ecosystems will be a
      critical influence on tree seedling response to increasing atmospheric CO(2)
      partial pressures.

PMID- 14967662
TI  - Adaptation to climatic changes of the timing of bud burst in populations of Pinus
      sylvestris L. and Picea abies (L.) Karst.
AB  - To assess the long-term effects of the projected climatic change on Scots pine
      and Norway spruce in Finland, observations were made on the timing of bud burst
      in provenance experiments established in 1931-1932 and in 1978. Significant
      differences in the timing of bud burst were found between seed origins. The
      northernmost origins flushed earlier than origins from southern regions. However,
      no correlation was found between the effective temperature sum at which bud burst
      took place and the annual mean temperature sum at the original location, probably
      because the experiments included origins from southerly high-altitude sites. When
      the degree days before bud burst in the 1931 and 1978 Norway spruce experiments
      at Punkaharju were compared, it appeared that, in the older experiment, the
      populations had adapted to the environment at the new site as a result of
      selective thinning.

PMID- 14967663
TI  - Dependence of light interception efficiency of Scots pine shoots on structural
      parameters.
AB  - The ratio of shoot silhouette area to total needle area (STAR) is one means of
      quantifying the light interception efficiency of a coniferous shoot. The
      silhouette area (or STAR) of a shoot depends on various structural
      characteristics of the shoot, and also varies with the direction of the shoot
      relative to the direction of radiation (sun angle). The mean STAR taken over all
      directions in space is the mean ratio of shoot silhouette area to total needle
      area in an isotropic radiation field. It also represents a mean STAR with respect
      to a spherical shoot orientation. In this study, equations for the relationship
      between mean STAR and easily measurable shoot characteristics were developed. The
      STAR values in different directions were determined from photographically
      measured shoot silhouette areas. Mean STAR varied between 0.079 and 0.308, and
      averaged 0.146. A clear increase in mean STAR with age was found. The material
      consisted of 305 Scots pine (Pinus sylvestris L.) shoots from Sweden and Finland,
      representing shoots of different age and a wide variation in site fertility. The
      needle area density in the shoot cylinder, together with the diameters of the
      shoot cylinder and the twig explained 87% of the variation in mean STAR.

PMID- 14967664
TI  - Performance of the LAI-2000 plant canopy analyzer in estimating leaf area index
      of some Scots pine stands.
AB  - The LAI-2000 plant canopy analyzer (Li-Cor, Inc., Lincoln, NE) was tested at six
      experimental plots of Scots pine (Pinus sylvestris L.) in central Sweden at peak
      leaf area in August and after litterfall in October 1990. An independent estimate
      of leaf area index for August 1990 was obtained based on an empirically derived
      regression of needle area on stem sapwood area, and the decrease in leaf area
      between the two measurements was estimated from measurements of litterfall. A
      strong linear relationship was found between estimates by the LAI-2000 (L(Li
      Cor)) and the indirect estimates of leaf area index (taken as half of total
      surface area) (L). The finding that L(Li-Cor) was considerably smaller than L was
      explained theoretically. It was shown that if shoots, instead of individual
      needles, are randomly distributed in the canopy, L(Li-Cor) corresponds to L
      multiplied by a factor (beta) characterizing the mutual shading of needles on the
      shoot. The shading factor, beta, was equal to the ratio of spherically projected
      shoot area to spherically projected needle area, where the spherically projected
      area is defined as the average projection (silhouette) area taken over all
      directions in space. The quantity betaL was defined as the shoot silhouette area
      index (SSAI), and an equation for the relationship between SSAI and the mean
      silhouette to total area ratio (mean STAR) of shoots was derived. Measured values
      of mean STAR for Scots pine indicated that L(Li-Cor) corresponds to SSAI rather
      than L. However, the decrease in leaf area index due to litterfall occurring
      between August and October was only partly detected by the LAI-2000, possibly
      because SSAI did not change to the same degree as L, i.e., there was an increase
      in the factor beta. This hypothesis is supported by data showing a large increase
      in mean STAR with shoot age.

PMID- 14967665
TI  - Evapotranspiration of beech stands and transpiration of beech leaves subject to
      atmospheric CO(2) enrichment.
AB  - Beech trees (Fagus sylvatica L.) show reduced stomatal conductance and increased
      leaf area index in response to increased atmospheric CO(2) concentration. To
      determine whether the reduction in stomatal conductance results in lower stand
      evapotranspiration, we compared transpiration on a leaf-area basis and stand
      evapotranspiration on a ground-area basis in young European beech trees growing
      in greenhouses at ambient (360 +/- 34 micro mol mol(-1)) and elevated (698 +/- 10
      micro mol mol(-1)) CO(2) concentrations. Trees were grown in homogenized natural
      soil at constant soil water supply for two growing seasons. At light saturation,
      leaf transpiration rates were, on average, 18% lower in the elevated CO(2)
      treatment than in the ambient CO(2) treatment. Mean transpiration coefficients
      (transpiration/net CO(2) uptake) of leaves were 179 and 110 in the ambient and
      elevated CO(2) treatments, respectively, indicating improved water use efficiency
      in trees in the elevated CO(2) treatment. Total leaf conductance was decreased by
      32% at light saturation. The elevated CO(2) treatment resulted in a 14% reduction
      in stand evapotranspiration. In both CO(2) treatments, evapotranspiration
      increased linearly at a rate of 0.2 kg H(2)O m(-2) day(-1) for each 1 degrees C
      rise in air temperature between 14 and 25 degrees C. We conclude that, under
      Central European conditions, water losses from deciduous forest stands will be
      reduced by a doubling of tropospheric CO(2) concentration.

PMID- 14967666
TI  - Water flux in a hybrid poplar stand.
AB  - We studied water flux in a four-year-old stand of hybrid Populus during midsummer
      1992. Study trees ranged in height from 11.0 to 15.1 m and in diameter from 8.3
      to 15.1 cm. The large-leafed Populus hybrid was relatively poorly coupled to the
      atmosphere. The average value of the stomatal decoupling coefficient, Omega, was
      0.66, indicating that, on average, a 10% change in stomatal conductance would
      result in only a 3 to 4% change in transpiration. During the middle of the
      summer, the smallest study tree used between 20 and 26 kg of water per day,
      whereas the largest tree used between 39 and 51 kg day(-1). The maximum observed
      rate of stand water loss was 4.8 mm day(-1) in this Populus clone. Maximum rates
      of sap velocity within the xylem were as high as 12.5 m h(-1); measured rates for
      exposed sunlit branches approached 90% of this maximum. Within-canopy patterns of
      stomatal conductance generally reflected patterns of incident radiation. Stomatal
      conductance of foliage grown in shade, even when exposed to non-limiting light
      and water source conditions, did not increase appreciably. Patterns of stomatal
      conductance under limiting and non-limiting conditions suggested that both
      stomatal conductance and leaf specific hydraulic conductivity (LSHC) were linked
      with the ability to exploit the light resource.

PMID- 14967667
TI  - Seasonal development of leaf area in a young, widely spaced Pinus radiata D. Don
      stand.
AB  - Measurements of needle elongation and needle death were made at two-week
      intervals during a year on 250 branch units spread throughout the crowns of six
      trees (three high-pruned, three low-pruned) in a widely spaced, 6- to 7-year-old
      Pinus radiata D. Don plantation in New Zealand. The trees were well supplied with
      nutrients and water. During the year, mean tree height increased by 1.2 m and the
      cross-sectional area of stem below the green crown (used to predict leaf area)
      for the average tree increased from 8.7 x 10(3) to 13.9 x 10(3) mm(2). The
      increase in stem cross-sectional area occurred throughout the year except for two
      months in early winter (May and June). Elongation of Age 0 needles began in
      Spring (October), continued through summer, and the mean date for 95% completion
      of elongation was in autumn (early May), approximately 200 days after elongation
      began. Mean maximum needle length in the canopy decreased with increasing branch
      order and was 136 and 94 mm for Order 1 and Order 3 units, respectively. Needle
      elongation was related to thermal time, using growing degree days with a base
      temperature of 6 degrees C. The mean maximum rate of needle elongation in the
      canopy was 0.11 m ( degrees C day)(-1) and this occurred in early summer (mid
      December), 47 days after elogation started. Maximum needle length and the rate of
      elongation increased, and the time taken to reach 95% elongation decreased with
      increasing height in the canopy. A smaller autumn flush of needles started in
      summer (January) and the needles elongated linearly at a mean rate of 0.07 mm (
      degrees C day)(-1) until the end of the growing season when temperatures fell
      below the base value. At the end of the year, the mean length of needles from the
      autumn flush was 66 mm. The density of needles did not change with height in the
      canopy and there were no significant changes seasonally. The mean density values
      for Age 1 and Age 0 needles were 336 and 286 kg m(-3), respectively. Dry weight
      per unit length did not change seasonally for Age 1 needles, but the mean values
      for Order 1 and Order 2 needles were 0.32 and 0.23 mg mm(-1), respectively. Dry
      weight per unit length for Age 0 needles increased during the growing season
      (October to February). This was particularly apparent for Order 1 needles where
      the mean value increased from 0.12 to 0.25 mg mm(-1). Death of Age 1 needles
      started in midsummer (mean date was January 24) which coincided with the time of
      maximum elongation of Age 0 needles, but there were differences in timing among
      individual trees. The mean rate of death was 1.7% day(-1) and the mean duration
      was 59 days. Leaf area index for the stand increased from 3.2 to 5.3 (all
      surfaces basis) during the year. At the end, 92% of the leaf area had grown
      during the year and 60% of it was on Order 2 branch units. The models for needle
      elongation and needle death were used to scale up to seasonal changes in canopy
      leaf area index. Leaf area index peaked with increasing Age 0 leaf area to 6.1 in
      summer (January), fell to 4.7 in March as Age 1 needles died, then increased
      slightly again. The seasonal dynamics are consistent with the hypothesis of
      Cannell (1989) that the timing of maximum leaf area index within a year is
      optimal for maximizing biomass production.

PMID- 14967668
TI  - Leaf water potential and stomatal conductance in Quercus pyrenaica Willd.
      forests: vertical gradients and response to environmental factors.
AB  - Two permanent sampling sites were selected at the two extremes of a rainfall
      gradient in natural forests of Quercus pyrenaica Willd. located in the Sierra de
      Gata (Salamanca Province, Spain). During 1991 and 1992, diurnal courses of
      transpiration rate (E), stomatal conductance (g(s)) and leaf water potential
      (Psi(l)) were studied at different levels in the tree canopy. Leaf water
      potential fell from a high value in the early morning to a minimum at midday and
      then increased again in the afternoon. Values of Psi(l) in the early morning and
      at midday were lower at Fuenteguinaldo (dry site) than at Navasfrias (wet site)
      and were related to soil water availability. Stomatal conductance increased
      during the morning and maximum g(s) occurred about 3 h before Psi(l) was at its
      lowest value. The highest values of g(s) were found at Navasfrias during July.
      The lowest Psi(l) values were found in the upper parts of the canopy and
      differences among canopy levels were greatest when soil water availability was
      low. In August, minimum values of Psi(l) differed among canopy levels by 1.0 MPa
      at Navasfrias and by 0.8 MPa at Fuenteguinaldo. The maximum difference in g(s)
      among canopy levels was about 150 mmol m(-2) s(-1) at Navasfrias and about 300
      mmol m(-2) s(-1) at Fuenteguinaldo. The results indicate a nonconservative
      pattern of water use in Quercus pyrenaica.

PMID- 14967669
TI  - Measurement of the remobilization of nitrogen for spring leaf growth of trees
      under field conditions.
AB  - Remobilization of N for leaf growth in the spring was studied in adjacent plots
      of Picea sitchensis and Acer pseudoplatanas. Before the onset of bud burst in
      April 1992, a solution of (15)NH(4) (15)NO(3) (enriched to 7.5 atom %) was
      applied to the soil, to supply 20 g N m(-2) over the total area of each plot. It
      was assumed that (15)N would remain in the soil nitrate- and ammonium-N pools,
      and so the appearance of (15)N in the leaves would indicate when soil N uptake
      started to contribute to leaf growth. Leaf N present before the appearance of
      (15)N from the fertilizer was assumed to be remobilized N. Growth of P.
      sitchensis needles continued for 45-50 days after bud burst, but their N content
      showed no consistent pattern throughout the spring and early sumer. The majority
      of needle N was already present at the initial samplings, immediately after bud
      burst, and any increases in needle N content occurred concomitantly with uptake
      of fertilizer (15)N. Acer pseudoplatanus leaves also grew for the duration of the
      experiment and their N content increased for the first 35 days after bud burst,
      reaching approximately 15 mg N leaf(-1). Acer pseudoplatanus leaves had
      approximately 5 mg N leaf(-1) before any (15)N was recovered, indicating that
      remobilization of N accounted for approximately one third of leaf N.

PMID- 14967670
TI  - Influence of tree size on shoot structure and physiology of Pinus contorta and
      Pinus aristata.
AB  - This study examined the morphological and physiological characteristics of shoots
      of large and small mature trees of two pine species with different growth
      patterns and tree longevities: Rocky Mountain bristlecone pine (Pinus aristata
      Bailey) and lodgepole pine (Pinus contorta Dougl. ssp. latifolia Bailey). Large
      trees of P. aristata had 21% less annual shoot growth but retained more total
      foliar biomass per shoot than small trees because of a 95% longer leaf life span.
      Large trees of P. contorta had 69% less annual shoot growth and less foliage
      production per shoot, and even with a 23% longer leaf life span, they retained
      leass total foliar biomass per shoot than small trees. Needles of both species
      and sizes did not begin to abscise until they reached approximately 40-45% of
      their expected maximum life span. Foliar nitrogen and phosphorus concentrations,
      N(mass) and P(mass), of 1-year-old P. aristata leaves were significantly lower
      and higher, respectively, in the large than in the small trees. In P. contorta,
      N(mass) and P(mass) of 1-year-old leaves were similar in large and small trees.
      Pinus aristata also had a more consistent N(mass) with leaf age than P. contorta,
      and the pattern differed for small and large trees. Photosynthetic capacity and
      stomatal conductance of 1-year-old leaves of P. aristata were less in large trees
      than in small trees. The increased plasticity in leaf life span with tree size in
      P. aristata compared with P. contorta enabled an increase in foliar biomass per
      shoot in P. aristata that may offset the decrease in photosynthetic performance
      and contribute to the smaller reduction in shoot growth with tree size in P.
      aristata compared with P. contorta. Similarities in needle biomass distribution
      between species and tree sizes suggest that relative needle age may be of greater
      importance to the retention of the leaves than their chronological age. The
      magnitude of the changes in shoot characteristics with increasing tree size
      differed between the species and may reflect alternative strategies of resource
      allocation and use.

PMID- 14967671
TI  - An analytical solution for coupled leaf photosynthesis and stomatal conductance
      models.
AB  - Iterative solutions of coupled leaf photosynthesis and stomatal conductance
      equations sometimes yield bifurcated or chaotic solutions. An analytical solution
      for coupled leaf photosynthesis-stomatal conductance equations is preferred
      because an analytical model has specific and known roots, and partial derivatives
      can be taken to perform sensitivity analyses. I present an analytical solution
      for coupled leaf photosynthesis and stomatal conductance equations that are based
      on established biochemical and physiological theory.

PMID- 14967672
TI  - A model for simulating the effects of changing climate on the functioning and
      structure of the boreal forest ecosystem: an approach based on object-oriented
      design.
AB  - We have developed a forest ecosystem model to assess the effects of climate
      change on the functioning and structure of boreal coniferous forests assuming
      that temperature and precipitation are the major variables of the niche occupied
      by a tree species. We specified weather patterns to a level representing the time
      constant of different physiological and ecological processes relevant to the
      survival, growth and death of trees. We thereby coupled the long-term dynamics of
      the forest ecosystem with climate through physiological mechanisms such as
      photosynthesis and respiration in terms of energy flow through the ecosystem. The
      hydrological and nutrient cycles couple the dynamics of the forest ecosystem with
      climate change through soil processes, which represent the thermal and hydraulic
      properties of the soil, and the decomposition of litter and humus with
      mineralization of nutrients. Simulations for southern Finland (62 degrees N)
      indicated that an increase in temperature of 5 degrees C over one hundred years
      could reduce soil water in Scots pine-dominated forest ecosystems. At the same
      time, the temperature increase could enhance photosynthesis up to 6-8% under
      current CO(2) concentrations (330 ppm) and up to 8-10% under elevated CO(2)
      concentrations (660 ppm). Because the elevated temperature and CO(2)
      concentration caused an increase in respiration (12-14% more than under the
      current climate), total stem production increased only up to 4% with a 5 degrees
      C increase in temperature and up to 6% when temperature and atmospheric CO(2)
      concentration were increased simultaneously. Because transpiration only increased
      up to 5% in response to elevated temperature and CO(2) concentration, the water
      use efficiency of Scots-pine dominated forest ecosystems increased up to 3%,
      particularly during the late rotation.

PMID- 14967673
TI  - Seasonal changes in bud dormancy in relation to bud morphology, water and starch
      content, and abscisic acid concentration in adult trees of Betula pubescens.
AB  - Annual cycles of change in bud morphology, bud burst ability, abscisic acid (ABA)
      concentration, and starch and water content were studied in mid-crown terminal
      buds of short shoots and underground basal buds of Betula pubescens Ehrh. In
      particular, we investigated the roles of ABA and bud water content in the
      regulation of bud growth. Basal buds differed morphologically from terminal buds
      of short shoots in that their leaf initials did not develop into embryonic
      foliage leaves and their total size did not increase significantly during summer.
      Bud burst ability, measured by forcing detached short shoots and stumps under
      controlled conditions, was maintained in the basal buds throughout the year,
      whereas the terminal buds of short shoots remained dormant until October,
      thereafter their bud burst ability increased gradually and reached a maximum in
      March-April. The ABA concentration of the basal buds was relatively constant
      throughout the sampling period (1-3 micro g g(DW) (-1)), whereas that of the
      terminal buds of short shoots, which was much higher (5-10 micro g g(DW) (-1)),
      showed a distinct seasonal cycle with a maximum from August to November. Bud ABA
      concentration decreased during the first 10 days of forcing, especially in basal
      buds. In both bud types, the amount of starch increased toward the autumn,
      declined in November, and was negligible in the terminal buds of short shoots
      between January and March, but in April, the amount was high again in both bud
      types. Water content varied characteristically in both bud types, although more
      distinctly in the terminal buds of short shoots, with an increase in spring
      before bud burst and a decrease during the summer until September. The
      significant morphological and physiological differences between the mid-crown
      terminal buds of short shoots and the underground basal buds may partly explain
      the characteristic growth habit of the basal buds and their development into
      coppice shoots after cutting the tree. The results also indicate a role for ABA
      in maintaining dormancy of the terminal buds of short shoots and emphasize the
      relationship between tissue water status and ABA concentration.

PMID- 14967674
TI  - Seasonal biochemical changes in coniferous forest canopies and their response to
      fertilization.
AB  - Seasonal changes in concentrations of total nitrogen, free amino acids,
      chlorophyll, starch and sugar were measured in foliage from fertilized and
      unfertilized conifer forests in New Mexico and Oregon. In the New Mexico Douglas
      fir (Pseudotsuga menziesii var glauca (Beissn.) Franco) forest, fertilization
      resulted in elevated foliar nitrogen concentrations on all dates, from an average
      of 9 mg g(-1) in unfertilized trees to 14 mg g(-1) in fertilized trees. In the
      Oregon western hemlock (Tsuga heterophylla (Raf.) Sarg.) forest, fertilization
      increased total N by only 15%, from 13 mg g(-1) in unfertilized trees to 15 mg g(
      1) in fertilized trees. Foliar nitrogen concentrations on a weight basis were
      lowest in winter and spring, but did not vary seasonally when expressed on a leaf
      area basis. Chlorophyll concentrations increased with fertilization and had
      greater seasonal variation than did total nitrogen concentrations. Chlorophyll
      concentrations were significantly higher during the growing season than in the
      winter and spring months. Fertilization did not result in major changes in the
      proportion of total nitrogen in chlorophyll at either the Oregon or the New
      Mexico site. Concentrations of free amino acids varied with date and
      fertilization treatment; in New Mexico, amino acids were highest in the winter
      sample, whereas in Oregon, they were lowest in winter and spring. At both sites,
      amino acid concentrations were significantly higher in fertilized trees than in
      control trees on most dates and the ratios of amino acid-N to total N were also
      significantly higher in fertilized trees. For both sites, starch concentrations
      were nearly zero for most of the year, but increased sharply just before bud
      break and initiation of new growth in the spring. Although fertilization resulted
      in increased nitrogen concentrations in foliage at both sites, the response in
      New Mexico was much greater than in Oregon. These results are in agreement with
      forest productivity data that suggest that growth in the New Mexico site is
      limited by nitrogen, whereas in the Oregon site it is not.

PMID- 14967675
TI  - Organic solute accumulation and dehydration tolerance in three water-stressed
      Populus deltoides clones.
AB  - The relationship between osmotic potential, water-soluble organic solutes and
      electrolyte leakage was investigated in three greenhouse-grown eastern cottonwood
      (Populus deltoides Bartr.) clones. The Ohio Red (from southern Ohio) and Platte
      (from eastern Nebraska) clones were selected because they differ in dehydration
      tolerance, gas exchange and osmotic potential. A third clone, Wildcat (from
      western Nebraska) was included because of its origin in a very dry area. Plants
      were either watered daily (control) or watered every 4-6 days (preconditioned). A
      third group of plants was watered daily until it was water-stressed at the end of
      the experiment (nonconditioned). Leaves for osmotic potential and water-soluble
      solute determinations were sampled at predawn after plants were rewatered. All
      clones showed osmotic adjustment ranging from 0.23 to 0.48 MPa. Organic solutes
      contributed up to 48% of the total osmotic adjustment. The solutes that
      contributed at least -0.05 MPa each to leaf osmotic potential in any clone were
      sucrose, malic acid, glucose, fructose, myoinositol and salicin. Fructose and
      glucose concentrations were unchanged or declined in preconditioned Ohio Red and
      Platte but increased in Wildcat. The Ohio Red clone had the highest sucrose
      concentration in both well-watered and preconditioned plants, and a lower injury
      index (more membrane stability) than Wildcat in the preconditioned plants,
      whereas nonconditioned Platte displayed the greatest electrolyte leakage of all
      clones and treatments. Cell membrane stability was correlated to osmotic
      potential and sucrose concentration only in Ohio Red.

PMID- 14967676
TI  - Effects of elevated nitrate and aluminum on the growth and nutrition of red
      spruce (Picea rubens) seedlings.
AB  - Acidic deposition in high-elevation forests in the Appalachian Mountains of the
      eastern United States has been implicated in the decline of red spruce (Picea
      rubens Sarg.). Elevated soil acidity may increase soil Al availability and
      toxicity to roots. Enhanced soil solution NO(3) (-) concentrations, resulting
      from precipitation inputs and enhanced soil organic matter mineralization, may
      exacerbate Al toxicity by increasing root Al uptake. We exposed red spruce
      seedlings to 350, 500, 800 or 1400 micro M NO(3) (-) and 0 or 200 micro M Al in a
      factorial design in sand-nutrient solution culture to test if increased NO(3) (-)
      concentrations enhance Al uptake and toxicity. In addition to significant
      reductions in seedling growth parameters resulting from Al exposure, we found
      significant interactions between NO(3) (-) and Al for seedling height growth
      rate, needle weight, shoot weight and root weight. Differences in these
      parameters between Al treatments became more pronounced as solution NO(3) (-)
      concentration increased and reflected an Al-mediated inhibition of seedling
      response to increasing NO(3) (-) concentration. Solution NO(3) (-) concentrations
      above 500 micro M induced root nitrate reductase (NR) activity, whereas shoot NR
      activity increased in response to NO(3) (-) up to 500 micro M and declined above
      that concentration. In contrast, exposure to Al depressed NR activity of roots
      but tended to stimulate needle NR activity. Foliar N concentrations increased in
      seedlings grown in cultures containing between 350 and 500 micro M NO(3) (-),
      with no change above 500 micro M. Increasing concentrations of NO(3) (-)
      depressed foliar P concentrations, with reductions being greatest in seedlings
      exposed to 1400 micro M NO(3) (-). Exposure to Al increased foliar Ca, K and Al
      concentrations, decreased foliar P concentrations, and inhibited increases in
      foliar Mg concentration in response to increasing NO(3) (-). The consistent
      interactions between NO(3) (-) and Al for growth, root NR activity and foliar Mg
      concentration were the result of an inhibition of seedling response to NO(3) (-)
      mediated by Al in solution, rather than enhanced Al toxicity resulting from
      growth in the presence of elevated NO(3) (-) concentrations.

PMID- 14967677
TI  - Site-specific water relations and stomatal response of Quercus ilex in a
      Mediterranean watershed.
AB  - Intraspecific variations in the water relations and stomatal response of Quercus
      ilex L. were analyzed under field conditions by comparing trees at two locations
      within a Mediterranean watershed (l'Avic, Catalonia, NE Spain). Distinct
      environmental gradients exist between the two sites (referred to as ridge top at
      975 m and valley bottom at 700 m) with greater soil depth for water storage,
      reduced radiation, reduced wind and higher water vapor pressure deficits at the
      valley bottom than at the ridge top. Osmotic adjustment and changes in tissue
      elasticiity did not significantly increase drought resistance in the trees
      studied. The leaf-to-air vapor pressure difference (Deltaw) threshold for
      inducing stomatal closure was higher at the ridge top (15.6 kPa MPa(-1) +/- 0.5
      SE) than at the valley bottom (9.8 kPa MPa(-1) +/- 1.0 SE). However, increases in
      Deltaw beyond the threshold were followed by greater reductions in leaf
      conductance of trees at the ridge top than at the valley bottom. At both sites,
      maximum leaf conductance was related to predawn shoot water potential which, in
      turn, was related to watershed stream flow. The effects of water deficits during
      the dry summer of 1989 were more severe in trees at the valley bottom than at the
      ridge top. During periods of high evaporative demand, site-specific differences
      in the control of water loss led to more conservative water use by trees at the
      ridge top and, thus, to even greater drought avoidance (higher predawn water
      potentials) in late summer.

PMID- 14967678
TI  - Photosynthesis and water-use efficiency of sugar maple (Acer saccharum) in
      relation to pear thrips defoliation.
AB  - An experimental introduction of pear thrips (Taeniothrips inconsequens Uzel), a
      major defoliator in sugar maple (Acer saccharum Marsh.) forests in northeastern
      North America, was conducted in a field plantation to determine if compensatory
      gas exchange occurs in response to feeding damage by this piercing-sucking
      insect. Sugar maple trees were enclosed in netting (167 micro m mesh) and pear
      thrips adults were introduced before leaf expansion in the spring. Pear thrips
      reduced whole-tree leaf area by approximately 23% and reduced leaf size (both
      mass and area) by 20% in the upper crown. Measurements of net CO(2) assimilation
      rate (A(net)) and stomatal conductance (g(s)) were made on tagged foliage that
      was later analyzed for stable carbon isotope composition (delta(13)C) to provide
      estimates of short- and long-term leaf water use efficiency (WUE). Pear thrips
      feeding reduced A(net) for fully expanded leaves by approximately 20%, although
      leaf chlorophyll content and leaf mass per unit area were apparently not
      affected. Comparison of A(net), g(s), instantaneous WUE and leaf delta(13)C
      between damaged and control trees as well as visibly undamaged versus moderately
      damaged foliage on pear thrips-infested trees indicated that there were no
      effects of pear thrips feeding damage on WUE or leaf delta(13)C. Long-term WUE
      among sugar maple trees in the field plantation, indicated by leaf delta(13)C
      analysis, was related to shorter-term estimates of leaf gas exchange behavior
      such as g(s) and calculated leaf intercellular CO(2) concentration (C(i)). We
      conclude that pear thrips feeding has no effect on leaf WUE, but at the
      defoliation levels in our experiment, it may reduce leaf A(net), as a result of
      direct tissue damage or through reduced g(s). Therefore, even small reductions in
      leaf A(net) by pear thrips feeding damage may have an important effect on the
      seasonal carbon balance of sugar maple when integrated over the entire growing
      season.

PMID- 14967679
TI  - Leaf growth, photosynthesis and tissue water relations of greenhouse-grown
      Eucalyptus marginata seedlings in response to water deficits.
AB  - Leaf growth, rate of leaf photosynthesis and tissue water relations of shoots of
      Eucalyptus marginata Donn ex Sm. (jarrah) seedlings were studied during a soil
      drying and rewatering cycle in a greenhouse experiment. Rates of leaf growth and
      photosynthesis were sensitive to water deficits. The rate of leaf growth
      decreased linearly with predawn leaf water potential to reach zero at -1.5 MPa.
      Rate of leaf growth did not recover completely within the first three days after
      rewatering. Midday photosynthetic rates declined to 40% of those of well-watered
      seedlings at a predawn leaf water potential of -1.0 MPa and reached zero at -2.2
      MPa. Photosynthetic rate recovered rapidly following rewatering and almost fully
      recovered by the second day after rewatering. All tissue water relations
      parameters, except the bulk modulus of elasticity, changed significantly as the
      soil dried and recovered completely by the third day after rewatering. Changes in
      osmotic pressure at full turgor of 0.4 MPa indicated considerable capacity for
      osmotic adjustment. However, because there was little osmotic adjustment until
      predawn leaf water potential fell below -1.5 MPa, this capacity would not have
      enhanced seedling growth, although it may have increased seedling survival. The
      sensitivity of photosynthesis and relative water content to water deficits
      suggests that greenhouse-grown E. marginata seedlings behave like mesophytic
      plants, even though E. marginata seedlings naturally grow in a drought-prone
      environment.

PMID- 14967680
TI  - Effects of short-term ozone exposure and soil water availability on the carbon
      economy of juvenile Douglas-fir.
AB  - Effects of ozone and soil water availability on partitioning and translocation of
      assimilates were studied in three-year-old Douglas-fir (Pseudotsuga menziesii
      [Mirb.] Franco) seedlings exposed, in separate experiments, to 0 and 106 or 0 and
      514 micro g m(-3) ozone for 8 h day(-1) for 9 days. The dynamics of carbon from
      assimilated (14)CO(2) were followed. No interactions between ozone and soil water
      content were observed. Total net uptake of carbon was reduced by low soil water
      content, but was unaffected by ozone. Both ozone and low soil water content
      increased the amount of (14)C-photosynthates retained in the current-year
      needles. Total starch content in old and current-year needles was unaffected by
      ozone, but was reduced by low water availability. Translocation of carbon to the
      root-soil compartment was additively affected by ozone and low soil water
      content. The results suggest that dry periods in summer combined with high ozone
      concentrations cause the greatest reduction in the supply of carbon compounds to
      the root-soil compartment.

PMID- 14967681
TI  - Photosynthesis, water relations, and growth of planted Pinus strobus L. on burned
      sites in the southern Appalachians.
AB  - We measured net photosynthesis, leaf conductance, xylem water potential, and
      growth of Pinus strobus L. seedlings two years after planting on two clear-cut
      and burned sites in the southern Appalachians. Multiple regression analysis was
      used to relate seedling net photosynthesis to vapor pressure deficit, seedling
      crown temperature, photosynthetically active radiation (PAR), needle N, xylem
      water potential, and soil water, and to relate seedling size and growth to
      physiological measurements (average net photosynthesis, leaf conductance, and
      cumulative xylem water potential), soil water, needle N, seedling temperature,
      and PAR. Seedling net photosynthesis was significantly related to vapor pressure
      deficit, midday water potential, crown temperature, and PAR (r(2) = 0.70) early
      in the growing season (May 1992) with vapor pressure deficit alone explaining 42%
      of the variation. As neighboring vegetation developed, light became more limiting
      and significantly reduced seedling net photosynthesis later in the growing season
      (July, August, and September). Final seedling diameter was significantly related
      to competitor biomass, average photosynthetic rate, and needle N (r(2) = 0.68).

PMID- 14967682
TI  - Vulnerability to drought-induced cavitation of riparian cottonwoods in Alberta: a
      possible factor in the decline of the ecosystem?
AB  - Vulnerability of xylem to loss of hydraulic conductivity caused by drought
      induced cavitation was determined for three riparian cottonwood species in
      Lethbridge, Alberta: Populus deltoides Bartr., P. balsamifera L., and P.
      angustifolia James. These species suffered 50% loss of hydraulic conductivity in
      one-year-old stem segments when xylem pressure potential fell to -0.7 MPa for P.
      deltoides and -1.7 MPa for P. balsamifera and P. angustifolia, making them the
      three most vulnerable tree species reported so far in North America. The possible
      contribution of drought-induced xylem dysfunction to the decline of riparian
      ecosystems in dammed rivers is discussed.

PMID- 14967683
TI  - Dependence of the aboveground respiration of hinoki cypress (Chamaecyparis
      obtusa) on tree size.
AB  - Nighttime respiration was measured at monthly intervals over one year on the
      aboveground parts of five sample trees in an 8-year-old hinoki cypress
      (Chamaecyparis obtusa (Sieb. et Zucc.) Endl.) stand, by an enclosed standing-tree
      method. The respiration rate rose rapidly from early spring to a maximum in June,
      and decreased abruptly in July and then gradually toward autumn and winter. The
      seasonal change in the respiration rate was synchronized with stem volume
      increment rather than with monthly mean air temperature. The respiration rate, r,
      of individual trees increased with increasing tree dimensions, such as stem
      volume, v(S), and stem girth at the base of the live crown, G(B). The dependence
      of respiration rate on tree size was successfully represented by a power
      function. The r - v(S) dependence was rather stronger than the r - G(B) (2)
      dependence, especially toward the end of the growing season (from July to
      September). The observed respiration rate was almost the same as the respiration
      rate corrected for the monthly mean air temperature. The annual respiration of
      individual trees was directly proportional to their phytomass or to its
      increment. Although the annual respiration of individual trees decreased
      proportionally to the square root of the leaf mass, it decreased abruptly in the
      range close to the smallest sample tree. Combining the monthly relationship
      between respiration rate and stem volume with the tree size distribution in the
      stand, the stand aboveground annual respiration was estimated to be 20.4 Mg CO(2)
      ha(-1) year(-1) (= 12.5 Mg dry mass ha(-1) year(-1)) for an aboveground biomass
      of 17.4 Mg ha(-1) with an annual increment of 6.51 Mg ha(-1) year(-1), i.e., the
      stand aboveground annual respiration amounted to the equivalent of 72% of the
      biomass or to almost twice the biomass increment.

PMID- 14967684
TI  - Movement of respiratory CO(2) in stems of loblolly pine (Pinus taeda L.)
      seedlings.
AB  - Temperature-independent fluctuations in stem CO(2) efflux were measured in Pinus
      taeda L. seedlings. Stem CO(2) efflux was measured during high and low
      transpiration rates, high and low net photosynthesis rates, and normal and
      interrupted substrate supply conditions. Stem CO(2) efflux rates were an average
      of 6.7% lower during periods of high transpiration compared to periods of low
      transpiration. This difference in stem CO(2) efflux rates was not due to water
      stress. The most likely cause was movement of respiratory CO(2) in the
      transpiration stream. Interruption of substrate supply to the stem by phloem
      girdling reduced stem CO(2) efflux rates. Increasing net photosynthesis rates
      from low to high had no effect on stem CO(2) efflux, but decreasing net
      photosynthesis from high to low caused relatively small reductions in stem CO(2)
      efflux. These results indicate that diurnal changes in net photosynthesis rate
      may play a small role in temperature-independent afternoon depressions of stem
      CO(2) efflux. The transport of respiratory CO(2) by the transpiration stream
      compromises measurements of woody tissue respiration obtained by commonly
      accepted gas exchange techniques. This phenomenon could also affect measurement
      of leaf net photosynthesis and branch woody tissue respiration.

PMID- 14967685
TI  - Partial shoot removal increases net CO(2) assimilation and alters water relations
      of Citrus seedlings.
AB  - Effects of defoliation on partial shoot removal by decapitation on seedling
      growth, water use and net gas exchange of remaining basal leaves, were examined
      in Citrus spp. Shoot and root growth rates were manipulated to test for effects
      of growth demands on net gas exchange. Partially defoliated plants had higher
      leaf pressure potentials, root conductivities and rates of water use than intact
      control plants. Shoot regrowth occurred at the expense of root loss. Basal leaves
      on defoliated plants consistently had higher rates of CO(2) assimilation (A) than
      leaves on intact plants. Stomatal conductance (g(s)) changed little after
      defoliation so the higher A of leaves on defoliated plants lowered the ratio of
      intercellular to ambient CO(2) concentration (C(i)/C(a)) in the mesophyll. In
      some cases, g(s) increased with A in defoliated plants but C(i)/C(a) was not
      affected. Stomatal conductance only limited A when intact seedlings were stressed
      by root confinement in small pots or when leaves were exposed to high vapor
      pressure deficits during gas exchange measurements. Increased carbon demand for
      shoot regrowth increased photosynthetic capacity and was more important than
      stomatal responses in determining A after partial shoot loss.

PMID- 14967686
TI  - Changes in protein synthesis during drought conditioning in roots of jack pine
      seedlings (Pinus banksiana Lamb.).
AB  - The impact of drought conditioning on the ability of eight-week-old jack pine
      (Pinus banksiana Lamb.) seedlings to withstand drought was assessed. Two
      progressive cycles of drought conditioning significantly increased the survival
      of seedlings subjected to a subsequent prolonged drought. The in vivo
      accumulation of several root membrane proteins during drought conditioning was
      correlated with an increase in seedling survival. A group of root proteins,
      ranging in molecular mass from 43 to 47 kDa, increased accumulation during one
      cycle of drought conditioning and to a lesser extent during two cycles of drought
      conditioning. The accumulation of several low molecular mass membrane and soluble
      proteins also increased during drought conditioning, suggesting that these
      proteins may play an important role in the enhancement of drought tolerance. In
      vitro translation studies showed a general increase in the abundance of protein
      products encoded by mRNAs from drought-conditioned seedlings. Although the
      majority of the in vitro translation products appeared in both control and
      drought-conditioned seedlings, one mRNA encoding a 15 kDA translated protein was
      more prominent during the second cycle of drought conditioning.

PMID- 14967687
TI  - ELISA Quantitation and GC-MS identification of abscisic acid in stigma, ovary and
      pedicel of pollinated poplar flowers (Populus nigra L.).
AB  - A method of fractionation, quantitation and identification of abscisic acid (ABA)
      in poplar flowers is presented in the context of intra- and interspecific
      pollination studies in Populus nigra x P. nigra and P. nigra x P. deltoides,
      respectively. Poplar flowers were dissected into stigma, ovary and pedicel.
      Abscisic acid concentrations were measured at receptivity and 5 days after
      pollination in each part of the flower. Abscisic acid was fractionated by reverse
      phase HPLC followed by an enzyme-linked immunosorbent assay (ELISA) with anti-ABA
      polyclonal antibody and GC-MS identification of the immunoreactive ABA fractions.
      Samples were fractionated and ABA was identified by the presence of a cross
      reactive metabolite of ABA in the extracts. The interspecific cross (P. nigra x
      P. deltoides) had a high concentration of ABA in the pedicel, where abscission
      occurred, whereas in the intraspecific cross, ABA concentration in the pedicel
      was low. The results are discussed with reference to the control ABA exerts on
      the abscission of poplar flowers after interspecific incompatible pollinations.

PMID- 14967688
TI  - Stable carbon isotope discrimination, photosynthetic gas exchange, and growth
      differences among western larch families.
AB  - Photosynthetic gas exchange, stable carbon isotope discrimination (Delta), height
      and diameter were compared among five open-pollinated families of 12-year-old
      western larch trees growing in a common garden in Moscow, Idaho, USA.
      Statistically significant variation was detected among the families in the two
      growth traits, Delta and stomatal conductance to water vapor (g) (P </= 0.013),
      but differences among families in photosynthetic rate (A) and water-use
      efficiency (W) were not significant (P >/= 0.203). Water-use efficiency was
      strongly correlated with Delta (r = -0.95, P < 0.01). Neither growth trait was
      correlated with A (r </= 0.05, P > 0.93) and height was not significantly
      correlated with Delta (r = -0.75, P = 0.15). Tree diameter and Delta were
      significantly correlated (r = -0.92, P = 0.03). These results were strongly
      influenced by a single family. Both the variation in Delta and correlation trends
      between Delta and the growth traits height and diameter suggest the possibility
      of selecting for high water-use efficiency with the potential for simultaneous
      gains in height and diameter growth.

PMID- 14967689
TI  - Xylem sap composition of beech (Fagus sylvatica L.) trees: seasonal changes in
      the axial distribution of sulfur compounds.
AB  - During different phases of the annual growth cycle, xylem sap was collected from
      trunk segments of adult beech (Fagus sylvatica L.) trees by the water
      displacement technique. Irrespective of the height of the trunk, both sulfate and
      reduced sulfur compounds were detected in the xylem sap throughout the year.
      Sulfate was the predominant sulfur compound in all samples analyzed. Its
      concentration in the xylem sap varied between 10 and 350 micro mol l(-1), with
      highest concentrations in April, shortly before bud break. In contrast to other
      tree species, cysteine and not glutathione was the predominant thiol transported
      in the xylem sap of beech trees. The cysteine concentration ranged between 0.1
      and 1 micro mol l(-1). As observed for sulfate, maximum cysteine concentrations
      were found in April. Apparently, both sulfate and cysteine transport contribute
      to the sulfur supply of the developing leaves. Seasonal changes in the axial
      distribution of cysteine and sulfate differed, indicating differences in the
      source-sink relations of these sulfur compounds. High, but uniform, xylem sap
      sulfate concentrations in April may originate from balanced sulfate uptake by the
      roots, whereas high cysteine concentrations in April, increasing with increasing
      height of the trunk, may originate in part from protein breakdown in the trunk.
      Reversal of the axial distribution of xylem sap cysteine in late summer-early
      fall to higher concentrations in the lower part of the trunk than in the upper
      part of the trunk suggests that the upper part of the trunk becomes a sink for
      cysteine as a result of the synthesis of storage proteins at this time of the
      year.

PMID- 14967690
TI  - PEACH: A simulation model of reproductive and vegetative growth in peach trees.
AB  - The hypothesis that carbohydrate partitioning is driven by competition among
      individual plant organs, based on each organ's growth potential, was used to
      develop a simulation model of the carbon supply and demand for reproductive and
      vegetative growth in peach trees. In the model, photosynthetic carbon
      assimilation is simulated using daily minimum and maximum temperature and solar
      radiation as inputs. Carbohydrate is first partitioned to maintenance
      respiration, then to leaves, fruits, stems and branches, then to the trunk. Root
      activity is supported by residual carbohydrate after aboveground growth.
      Verification of the model was carried out with field data from trees that were
      thinned at different times. In general, the model predictions corresponded to
      field data for fruit and vegetative growth. The model predicted that resource
      availability limited fruit and stem growth during two periods of fruit growth,
      periods that had been identified in earlier experimental studies as resource
      limited growth periods. The model also predicted that there were two periods of
      high carbohydrate availability for root activity. The fit between model
      predictions and field data supports the initial hypothesis that plants function
      as collections of semiautonomous, interacting organs that compete for resources
      based on their growth potentials.

PMID- 14967691
TI  - Diurnal patterns of leaf photosynthesis, conductance and water potential at the
      top of a lowland rain forest canopy in Cameroon: measurements from the Radeau des
      Cimes.
AB  - Diurnal patterns of leaf conductance, net photosynthesis and water potential of
      five tree species were measured at the top of the canopy in a tropical lowland
      rain forest in southwestern Cameroon. Access to the 40 m canopy was by a large
      canopy-supported raft, the Radeau des Cimes. The measurements were made under
      ambient conditions, but the raft altered the local energy balance at times,
      resulting in elevated leaf temperatures. Leaf water potential was equal to or
      greater than the gravitational potential at 40 m in the early morning, falling to
      values as low as -3.0 MPa near midday. Net photosynthesis and conductance were
      typically highest during midmorning, with values of about 10-12 micro mol CO(2)
      m(-2) s(-1) and 0.2-0.3 mol H(2)O m(-2) s(-1), respectively. Leaf conductance and
      net photosynthesis commonly declined through midday with occasional recovery late
      in the day. Photosynthesis was negatively related to leaf temperature above
      midday air temperature maxima. These patterns were similar to those observed in
      other seasonally droughted evergreen communities, such as Mediterranean-climate
      shrubs, and indicate that environmental factors may cause stomatal closure and
      limit photosynthesis in tropical rain forests during the midday period.

PMID- 14967692
TI  - Leaf-level and whole-plant gas exchange characteristics of shortleaf pine exposed
      to ozone and simulated acid rain.
AB  - Field-grown shortleaf pine (Pinus echinata Mill.) seedlings were exposed to ozone
      (O(3)) and simulated acid rain (SAR) in open-top chambers over three growing
      seasons. Ranges of O(3) and SAR spanned ambient levels found in the southern USA.
      Effects of O(3) on leaf-level and whole-plant gas exchange were characterized for
      a single measurement period immediately before the third summer of exposure.
      Decreased photosynthesis rates were attributed to O(3), but not SAR. Stomatal
      conductance decreased in response to O(3) exposure, and either increased or was
      unaffected by SAR. Increased internal CO(2) concentration (c(i)) in response to
      O(3) treatment indicated a greater effect of O(3) on photosynthetic capacity than
      stomatal conductance. Whole-seedling gas exchange characteristics indicated that
      whole-seedling carbon assimilation was more severely affected by O(3) than was
      evident from leaf-level gas exchange characteristics. Seedlings exposed to O(3)
      retained fewer flushes than seedlings grown in charcoal-filtered air.

PMID- 14967693
TI  - Growth and nutrition of small Betula pendula plants at different relative
      addition rates of manganese.
AB  - In a series of experiments, growth of small birch plants (Betula pendula Roth)
      was controlled by the relative addition rate of manganese, R(Mn) (day(-1)). The
      R(Mn) treatments were 0.05, 0.10, 0.15 and 0.20 day(-1) with free access to all
      other nutrients. In an additional treatment, FA, there was free access to all
      nutrients including Mn. The pH of the nutrient solution ranged between 3.9 and
      4.1, and the conductivity was between 100 and 200 micro S cm(-1). After an
      adjustment phase to steady-state growth, there was a one-to-one relationship
      between the relative growth rate, R(G) (day(-1)), and the supply of manganese,
      R(Mn) (day(-1)). The Mn concentration of the plants ranged from 6 to 13 micro g
      g(DW) (-1) in all treatments with limiting R(Mn) and was approximately 200 micro
      g g(DW) (-1) in the FA treatment. At steady-state growth, the plants showed
      specific Mn deficiency symptoms, including leaf mortality, that were more
      pronounced at severe Mn limitation. Total nonstructural carbohydrate
      concentrations were low, less than 7.5% of dry weight at Mn limitation, and the
      fraction of plant dry matter partitioned to roots was much less at Mn limitation
      than has previously been reported for equivalent rates of N or P supply.
      Manganese uptake rate per unit root growth rate, dMn/dW(r) ( micro mol g(DW) (
      1)) was unaffected by the supply of Mn. At Mn limitation, low rates of plant
      growth were associated with high values of specific leaf area (37 versus 36 m(2)
      kg(DW) (-1)), and lower values of leaf weight ratio (40 versus 61%) and net
      assimilation rate (3 versus 10 kg(DW) (-1) m(-2) day(-1)) than were found at
      higher R(Mn).

PMID- 14967694
TI  - Distribution and retranslocation of (15)N lodgepole pine over eight growing
      seasons.
AB  - We studied the distribution and retranslocation of N in 11-year-old Pinus
      contorta Dougl. trees following a winter application of N at 100 kg ha(-1) as
      (15)N-urea, (15)NH(4)NO(3) or NH(4) (15)NO(3). In all treatments, there was
      little uptake of (15)N after the first growing season although labeled N was
      still present in the soil. In subsequent years, (15)N in the trees was partly
      retranslocated, and, at the same time, it was diluted by uptake of unlabeled N
      from the soil. Between Years 1 and 8 after N fertilization, net retranslocation
      of (15)N from the lower crown (branches formed before fertilization) was 14%, and
      18-25% of the (15)N in the trees was translocated to the upper and mid-crown.
      Overall, uptake of (15)N from nitrate was less than from urea or ammonium.
      However, when compared with the urea- and ammonium-N sources, (15)N from the
      nitrate source initially moved as rapidly into the foliage, but a greater
      proportion of it was retranslocated from the foliage during the second growing
      season. Nitrogen in foliage and wood formed in the growing season following
      fertilization was more highly labeled (measured as % N derived from the
      fertilizer) than in recently formed tissues. Labeling was substantially higher in
      foliage formed before fertilization than in wood of a similar age. In contrast, N
      in foliage formed after fertilization had only slightly higher labeling than wood
      of a similar age, indicating a relatively stable labeling throughout the trees
      once (15)N uptake had ceased. The concentrations of total and labeled N were
      substantially higher in foliage than in either wood or bark. There was evidence
      of N movement into wood tissues formed before fertilization, presumably along
      rays, and also of N retranslocation out of xylem cells as they matured. This
      study of internal N cycles was facilitated by the use of (15)N labeling because
      there was little uptake of labeled N after the first growing season, whereas
      interpretation based on total N was obscured by substantial uptake of N from the
      soil. We conclude that retranslocation studies based on measurements of total N
      content should be avoided.

PMID- 14967695
TI  - Accumulation of flavanols in yellowing beech leaves from forest decline sites.
AB  - Beech leaves were sampled during two consecutive years from three sites
      characterized by forest decline. Both monomeric and oligomeric flavanols from
      green and yellowing leaves were determined quantitatively by reversed-phase, high
      performance liquid chromatography (HPLC) combined with a chemical reaction
      detection technique (CRD). Yellowing leaves generally contained more than twice
      the quantity of flavanols than normal green leaves. The monomeric flavanols,
      epicatechin and (+)-catechin, comprised up to 80% of the total flavanol fraction.
      Histochemical staining with p-dimethylaminocinnamaldehyde was used to determine
      local deposition of flavanols, including insoluble oligomeric flavanols, in leaf
      tissues. The yellowing leaves stained intensely, whereas the green leaves stained
      lightly. Flavanol staining was strongest in the spongy parenchyma followed by the
      palisade cells. The upper epidermis stained more intensely than the lower
      epidermis. A 4-day treatment of small leaf pieces (5 x 5 mm) with 0.04 mM
      paraquat resulted in browning of the leaf pieces. The browning reaction was
      prevented when the paraquat treatment was carried out in the presence of 0.16 mM
      (+)-catechin, indicating an antioxidative property for this flavanol.

PMID- 14967696
TI  - Effects of soil freezing and drought stress on abscisic acid content of sugar
      maple sap and leaves.
AB  - In 1991 and 1992, mature maple trees (Acer saccharum Marsh.) were freeze-stressed
      or drought-stressed by preventing precipitation (snow or rain) from reaching the
      forest floor under selected trees. Lack of snow cover caused a decrease in soil
      temperature to well below 0 degrees C from December to April and a lowering of
      the soil water content to 10%. The abscisic acid (ABA) concentration in the
      spring sap of deep-soil frost-stressed trees was significantly higher than in
      control or drought-stressed trees. The increase in ABA concentration in the xylem
      sap in the spring of 1991 and 1992 preceded symptoms of canopy decline and a
      decrease in leaf area that were observed during the summers of 1991 and 1992.
      These results suggest a role for ABA in root-to-shoot communication in response
      to environmental stress. The largest differences in ABA concentration induced by
      the treatments was found in sap collected at the end of sap flow. The increase in
      ABA concentration in spring sap at the end of the sap flow could be used as an
      early indicator of stress suffered by trees during the winter. Not only did the
      increase in ABA concentration occur before any visible symptoms of tree decline
      appeared, but the trees that showed the most evident decline had the highest ABA
      concentrations in the spring sap. Leaf ABA concentration was not a good indicator
      of induced stress.

PMID- 14967697
TI  - Growth and branching habit of rooted cuttings collected from epicormic shoots of
      Betula pendula Roth.
AB  - Patterns of shoot growth and branching were studied over two growing seasons in
      rooted cuttings collected from both epicormic shoots and seedlings of Betula
      pendula Roth. Epicormic shoots were induced to sprout on stumps and small logs of
      5-, 10- and 30-year-old trees. The use of epicormic shoots enhanced the rooting
      capacity of stem cuttings collected from these shoots but did not appear to
      reverse the process of maturation. In this study, maturation was based on
      characteristics typical of mature trees but not necessarily those of the mother
      plant, because it was not possible to root cuttings, for comparison, from 5-, 10-
      and 30-year-old ortets, other than from epicormic shoots. There was evidence of
      the persistence of mature characteristics through an increase in shoot
      plagiotropism with increasing ortet age. Rooted cuttings from both seedlings and
      epicormic shoots, however, assumed an increasingly orthotropic habit with a
      smaller shoot angle at the end of the first growing season than at the beginning
      and this continued into the second growing season. Other indications of
      maturation, such as delayed bud flushing and the incidence of flowering with
      increasing ortet age, were also evident in rooted cuttings from epicormic shoots.
      There was a clear difference in branching habit depending on cutting source.
      Rooted cuttings derived from epicormic shoots produced nearly twice as many
      lateral branches compared with rooted cuttings collected from seedlings, but this
      was not an effect of maturation. There was some evidence that rooted cuttings
      derived from seedlings grew taller than rooted cuttings from epicormic shoots.

PMID- 14967698
TI  - Patterns of hydraulic architecture and water relations of two tropical canopy
      trees with contrasting leaf phenologies: Ochroma pyramidale and Pseudobombax
      septenatum.
AB  - Many authors have attempted to explain the adaptive response of tropical plants
      to drought based on studies of water relations at the leaf level. Little
      attention has been given to the role of the xylem system in the control of plant
      water requirements. To evaluate this role, we studied the hydraulic architecture
      and water relations parameters of two tropical canopy trees with contrasting leaf
      phenologies: deciduous Pseudobombax septenatum (Jacq.) Dug and evergreen Ochroma
      pyramidale (Cav. ex lamb) Urban, both in the family Bombacaceae. The hydraulic
      architecture parameters studied include hydraulic conductivity, specific
      conductivity, leaf specific conductivity, and Huber value. Water relations
      parameters include leaf water potential, stem and leaf water storage capacitance,
      transpiration, stomatal conductance, and vulnerability of stems to cavitation and
      loss of hydraulic conductivity by embolisms. Compared to temperate trees, both
      species showed a pattern of highly vulnerable stems (50% loss of conductivity due
      to embolism at water potentials less than 1 MPa) with high leaf specific
      conductivities. The vulnerability of xylem to water-stress-induced embolism was
      remarkably similar for the two species but the leaf specific conductivity of
      petioles and leaf-bearing stems of the evergreen species, Ochroma (e.g., 9.08 and
      11.4 x 10(-4) kg s(-1) m(-1) MPa(-1), respectively), were 3.4 and 2.3 times
      higher, respectively, than those of the deciduous species, Pseudobombax (e.g.,
      2.64 and 5.15 x 10(-4) kg s(-1) m(-1) MPa(-1), respectively). A runaway embolism
      model was used to test the ability of Ochroma and Pseudobombax stems to maintain
      elevated transpiration rates during the higher evaporative demand of the dry
      season. The percent loss of leaf area predicted by the runaway embolism model for
      stems of Pseudobombax ranged from 5 to 30%, not enough to explain the deciduous
      phenology of this tree species without analysis of root resistance or leaf and
      petiole vulnerability to embolism.

PMID- 14967699
TI  - Formation and seasonal occurrence of xylem embolism in Alnus cordata.
AB  - We investigated the vulnerability of xylem to embolism and the seasonal
      occurrence of xylem embolism in Italian alder (Alnus cordata Loisel.) by acoustic
      and hydraulic methods. Wood anatomy was also studied. More than eighty percent of
      the vessels were less than 50 mm long and no vessels were longer than 120 mm.
      Mean vessel diameter was 48 micro m. Ultrasound acoustic emissions from root and
      branch segments dehydrating in air followed a similar pattern: in both tissues,
      emission peaks were recorded when the relative water content of the xylem was
      around 0.2. In branches dehydrating in air, xylem embolism increased linearly as
      water potential decreased. In trees in the field, more than 80 percent of
      hydraulic conductivity was lost in the tree crowns during winter. Recovery from
      winter embolism occurred mostly before bud burst. In summer, xylem embolism was
      low (< 30%) and acoustic emissions from roots, stem and branches of trees in the
      field were also low.

PMID- 14967700
TI  - Effects of flooding on leaf dynamics and other seedling responses in flood
      tolerant Alnus japonica and flood-intolerant Betula platyphylla var. japonica.
AB  - Two-year-old seedlings of Alnus japonica Steud. and Betula platyphylla var.
      japonica Hara were flooded from mid-June to early November, to study the effects
      of flooding on seedling survival and growth, morphological changes in stems and
      roots, leaf emergence, leaf fall, and leaf longevity. In A. japonica, growth was
      not affected by flooding, except for a slight decrease in height growth, but some
      morphological changes of stems and roots were observed, i.e., stem base
      hypertrophy, hypertrophied lenticels, formation of adventitious roots and
      development of new roots. In B. platyphylla var. japonica, growth was severely
      reduced by flooding and all seedlings died by the 20th week of flooding, without
      showing any adaptive morphological changes in stems or roots. Flooding induced
      rapid depression of leaf emergence, promoted leaf abscission, and reduced leaf
      longevity in B. platyphylla var. japonica. In contrast, in A. japonica, basal
      leaf senescence was delayed in flooded seedlings, thereby extending leaf
      longevity compared with unflooded seedlings.

PMID- 14967701
TI  - Influence of irradiance on photosynthesis, morphology and growth of mangosteen
      (Garcinia mangostana L.) seedlings.
AB  - The influence of shading intensity on growth, morphology and leaf gas exchange of
      mangosteen (Garcinia mangostana L.) seedlings was investigated over a 2-year
      period. Diurnal gas exchange studies revealed significantly higher carbon gain
      for leaves grown in 20 or 50% shade compared to leaves grown in 80% shade.
      Seedlings grown in 20 or 50% shade accumulated significantly more dry weight than
      seedlings grown in 80% shade during the 2-year study period. Seedlings grown in
      decreased shade showed decreased leaf size, increased leaf thickness, lower
      specific leaf area (SLA) and higher stomatal frequency. Less shaded seedlings
      also allocated relatively more dry matter to roots than shaded seedlings and
      exhibited a significant reduction in leaf area relative to total plant dry weight
      (leaf area ratio). Increased leaf number, enhanced branching and shorter
      internodes resulted in a more compact appearance of less shaded seedlings.
      Irrespective of light conditions, mangosteen seedlings exhibited inherently slow
      growth because of low photosynthetic rates per unit leaf area, low SLA, low leaf
      area ratios and inefficient root systems.

PMID- 14967702
TI  - Regulation of early flowering in Pinus banksiana.
AB  - Seedlings of three families of jack pine (Pinus banksiana Lamb.) were subjected
      to 16 combinations of photoperiod, growth environment (outdoors, greenhouse and
      biotron) and gibberellin (GA(4/7)) treatment. After 14 months, which included two
      dormancy induction periods, ovulate flowering was observed. There was a strong
      positive correlation between flowering and seedling height; female flower
      production was stimulated by both a declining photoperiod during bud development
      and GA(4/7) treatment; and there was an interaction between GA(4/7) treatment and
      family, such that the difference in flowering intensity between a late-flowering
      and an early-flowering family was eliminated by GA(4/7) treatment. The results
      suggest that the genetic control over the time of onset of flowering, and GA(4/7)
      induction of flowering depend on a common mechanism.

PMID- 14967703
TI  - Fluxes of Ca(2+), K(+) and Cl(-) across the surfaces of detached needles from
      Sitka spruce trees: pathways and compartmentation.
AB  - Uptake and efflux of (36)Cl(-), (45)Ca(2+) and (42)K(+) were measured in water
      infiltrated detached needles from Sitka spruce (Picea sitchensis (Bong.) Carr.)
      trees incubated in 1 mol m(-3) KCl or CaCl(2) or 2 mol m(-3) NaCl solutions or in
      artificial rain water containing mmol m(-3) amounts of these ions. Surface efflux
      was measured separately from leakage from the cut ends of the needles. Needles
      loaded with (36)Cl(-) and killed in liquid N(2) before elution displayed a rapid
      and extensive loss of radioisotope, indicating that mesophyll cell membranes were
      the limiting factor for (36)Cl(-) exchange. Data for live needles revealed a
      novel phase of (36)Cl(-) efflux, with an exchange halftime of about 20 min, which
      was faster than that for either the vacuole or the cytoplasm, but much slower
      than that for the free space. The novel phase was interpreted as representing
      diffusion of Cl(-) through the predominantly negatively charged cuticle. Killing
      needles loaded with (45)Ca(2+) or (42)K(+) also increased efflux relative to that
      from live needles, but only to a limited degree, indicating that the main factor
      limiting cation efflux was the cuticle. During the first hours of (45)Ca(2+)
      uptake, the isotherms displayed a shoulder, indicating that there was a
      significant Donnan free space phase in the cuticle for Ca(2+). A shoulder was
      absent from (42)K(+) uptake isotherms because of the preferential adsorption of
      divalent cations on the exchange sites.

PMID- 14967704
TI  - Electric resistance as a measure of tree water status during seasonal drought in
      a tropical dry forest in Costa Rica.
AB  - Variation in electric resistance of stem tissues was used to measure differences
      and changes in water status among trees in a tropical dry forest in Costa Rica
      during the dry season. For more than 30 tree species, stem water content (SWC),
      measured as electric resistance between nails driven 20 mm deep into tree trunks,
      correlated well with wood density, saturation water content, dehydration,
      measured with the pressure chamber, and tree development during drought. At dry
      sites, SWC was lowest in hardwood trees (characterized by high wood density) and
      highest in stem-succulent lightwood trees (characterized by low wood density).
      Among hardwood trees, SWC varied with soil water availability. During the dry
      season, SWC declined before leaf shedding and increased during rehydration
      preceding bud break. The time course of seasonal changes in SWC apparently
      constitutes an indirect measure of variation in the relative water content of
      outer stem tissues, which determines development of dry-forest trees during the
      dry season.

PMID- 14967705
TI  - Aftereffects of maternal environment on autumn frost hardiness in Pinus
      sylvestris seedlings in relation to cultivation techniques.
AB  - Full-sib families of Pinus sylvestris (L.) from genetically identical parent
      clones, grown at three geographic locations (64, 59.5, and 56 degrees N), were
      tested for autumn frost hardiness. At one of the locations (64 degrees N),
      maternal clones were grown in plots subjected to different site treatments.
      Progenies raised in a heated greenhouse with additional artificial light were
      induced to undergo two shoot elongation periods, separated by a period with long
      nights and non-hardening temperatures, followed by a hardening period. Frost
      hardiness was tested by exposing seedlings to -17, -19, or -21 degrees C during
      the hardening period. Progenies produced at the northernmost locality (64 degrees
      N) were the most hardy. The hardiness ranking among localities and the magnitude
      of differences in hardiness were in accordance with earlier results obtained from
      the same crosses that had undergone only one shoot elongation period. Effects of
      maternal site treatments were significant but small compared with family
      differences. The growth regimes used in the present study did not eliminate
      maternal effects induced by geographic location, but maternal effects related to
      site treatment decreased substantially in relation to family variation when
      compared with seedlings that had undergone only a single shoot elongation period.
      The results are discussed in relation to other studies of the same crosses raised
      under different growth conditions.

PMID- 14967706
TI  - Effects of maternal environment on mortality and growth in young Pinus sylvestris
      in field trials.
AB  - The same full-sib families of Scots pine (Pinus sylvestris L.) were created by
      artificial pollination of genetically identical grafts at three localities in
      Sweden at approximately 56, 59 and 64 degrees N. Two field trials were
      established with one-year-old plants in different years at latitude 64 degrees N.
      Height and survival were monitored for 4-5 years following planting. Maternal
      environment had significant aftereffects on the height of progeny. In both field
      trials, plants with the maternal parent at 59 degrees N were tallest and plants
      with the maternal parent at 64 degrees N were shortest. The aftereffects of
      maternal environment were as large in six-year-old plants as in one-year-old
      plants. In one field trial, maternal environment had a significant effect on
      mortality six years after germination but not after three years. Mortality
      increased with decreasing latitude of the maternal location. We conclude that the
      aftereffects of maternal environment are too large and too permanent to be
      regarded as unimportant.

PMID- 14967707
TI  - Element concentrations in the xylem sap of Picea abies (L.) Karst. seedlings
      extracted by various methods under different environmental conditions.
AB  - We used a Scholander pressure chamber to assess the effects of various extraction
      methods under different environmental conditions on element concentrations in
      xylem sap of 3-year-old Picea abies (L.) Karst. seedlings. Sap from excised
      shoots contained higher element concentrations when extracted at low than at high
      over-pressures. When comparing plants differing in water status, we found that a
      high extraction over-pressure introduced a systematic error into the data. For
      example, in well-watered non-transpiring plants relative to unwatered transpiring
      plants, potassium concentrations were 70% higher in sap extracted at 0.1 MPa over
      pressure, but only 10% higher in sap extracted at 1.0 MPa over-pressure.
      Moreover, treatment effects depended on the time of day when the sap was
      extracted. Increased water flux in transpiring plants relative to non-transpiring
      plants resulted in reduced xylem sap element concentrations when samples were
      collected after 9 h of transpiration, but not after 4 to 6 h of transpiration.
      Drought had little effect on xylem sap element concentrations, indicating that
      rates of element release into xylem conduits, element depletion by growing
      tissues, and water flow maintained a balance that may prevent nutrient stress
      during short-term drought.

PMID- 14967708
TI  - Influence of water relations on Quercus cerris-Hypoxylon mediterraneum
      interaction: a model of drought-induced susceptibility to a weakness parasite.
AB  - The association between water stress and susceptibility of Quercus cerris to the
      fungal parasite Hypoxylon mediterraneum was studied in field-grown trees and
      greenhouse-grown seedlings. Susceptibility of Q. cerris to the fungus, expressed
      as extension of wood discolorations, increased in field-grown trees during
      drought and increased in greenhouse-grown seedlings in response to limited water
      supply. In both seedlings and trees, spread of the fungus in the vascular system
      was higher when leaf water potentials were low than when leaf water potentials
      were high, and was significantly correlated to loss of hydraulic conductivity of
      xylem. The presence of the fungus in the xylem suggests that H. mediterraneum
      could use embolized vessels to spread in the host.

PMID- 14967709
TI  - Carbohydrate mobilization following shoot defoliation and decapitation in hybrid
      poplar.
AB  - The effects of shoot defoliation, decapitation, and disbudding on carbon
      mobilization were investigated in rooted cuttings of Populus maximowiczii x nigra
      L. 'MN9'. Ten days after complete shoot defoliation or decapitation, the stem
      starch concentration of treated plants declined to one-half that of intact
      plants, and there were similar or greater reductions in the concentrations of
      glucose, fructose, sucrose, galactose, and shikimic acid. Partial shoot
      defoliation (50%) and complete disbudding had no effect on stem starch
      concentration, but stem sucrose concentration was reduced in all treatments.
      Sucrose depletion preceded and may have induced other changes in the carbon
      status of plants subjected to leaf or shoot removal. Four days after shoot
      decapitation, the sucrose concentration of roots of treated plants was reduced to
      25% of that of intact plants. However, the concentrations of fructose and glucose
      increased in the roots of treated plants and was followed by the accumulation of
      shikimic acid, salicyl alcohol, unknown compound A and salicin. The possible role
      of increased concentrations of root organic solutes in the water relations and
      regrowth process of decapitated plants is discussed.

PMID- 14967710
TI  - Partitioning of photoassimilates in avocado (Persea americana Mill.) during
      flowering and fruit set.
AB  - To assess competition for photoassimilates among developing inflorescences,
      fruitlets and vegetative shoots in avocado (Persea americana Mill.), the
      distribution of recent photoassimilates was examined before and during flowering,
      fruit set, and the transition from sink to source of developing vegetative
      shoots. Mature leaves, located proximal to developing reproductive organs, and
      developing leaves, located distal to those organs, were exposed to a one-hour
      pulse of (14)CO(2). Translocation of radiolabeled assimilates was monitored over
      time and among organs. Overall distribution of assimilates was dependent on dry
      mass of tissues regardless of organ type. Flowers and fruitlets did not
      demonstrate greater sink strength than non-autotrophic leaves. Organs receiving
      assimilates were in phyllotactic alignment with source leaves. Photoassimilates
      were never limiting, although flower and fruitlet abscission occurred during and
      long after this competitive period. Carbohydrate availability was sufficient to
      support the growth of both developing fruitlets and leaves during early stages of
      reproductive development, and it did not limit fruitlet growth or stimulate
      fruitlet abscission.

PMID- 14967711
TI  - Rubisco and PEP carboxylase responses to changing irradiance in a Brazilian
      Cerrado tree species, Qualea grandiflora Mart. (Vochysiaceae).
AB  - The activities of ribulose-1,5-bisphosphate carboxylase-oxygenase, Rubisco (E.C.
      4.1.1.39) and phosphoenolpyruvate carboxylase, PEPc (E.C. 4.1.1.31), and
      concentrations of protein and chlorophyll were measured in extracts from
      cotyledons and first leaves of Qualea grandiflora Mart. (Vochysiaceae) seedlings
      after transfer from high-light (20 days at 320 micro mol m(-2) s(-1), PAR) to low
      light (35 days at 120 micro mol m(-2) s(-1), PAR) conditions. When Tween 20 and
      glycerol were added to the extraction medium, Rubisco activities obtained for
      Qualea grandiflora were comparable to published values for several coniferous
      species and the broad-leaved species, Prunus avium L. Stella, grown in a similar
      light environment. Rubisco activity in cotyledons of Q. grandiflora grown in high
      light for 20 days and then transferred to low light for a further 35 days was
      similar to the activity in cotyledons of plants grown continuously in high light.
      However, the first leaf above the cotyledons showed a greater response to the
      change in irradiance; in high light, Rubisco activity of the first leaf was 1.8
      times higher on a fresh weight basis and 2.7 times higher on an area basis than
      that of leaves transferred from high to low light. Fresh weight and chlorophyll
      concentration expressed on a unit leaf area basis were also higher in the high
      light treatment. These responses to irradiance are indicative of a species
      adapted to growth in an unshaded habitat. The PEPc activity in leaves was 15% of
      Rubisco activity, which is typical of species with a C(3) photosynthetic pathway.
      The relatively slow growth rate of Q. grandiflora observed in these experiments
      could not be attributed to a low carboxylation capacity per unit leaf area.

PMID- 14967712
TI  - The effect of environmentally induced stem temperature gradients on transpiration
      estimates from the heat balance method in two tropical woody species.
AB  - Commercially available sap flow gauges were used to evaluate the performance of
      the stem heat balance (SHB) technique for measuring sap flow in coffee (Coffea
      arabica L. cv. Yellow Catuai) and koa (Acacia koa Gray) plants under greenhouse
      and field conditions. Transpiration rates measured gravimetrically and with the
      SHB technique were similar in greenhouse tests, provided that insulation in
      addition to that supplied by the gauge manufacturer was applied to reduce radiant
      heating in the vicinity of the sap flow gauges. Unrealistic estimates of
      transpiration rates were sometimes obtained under both field and greenhouse
      conditions as a result of negative stem temperature differentials from below to
      above the gauge heater, even in the absence of power applied to the heaters. It
      was possible to correct this environmentally induced bias by means of additional
      stem insulation that minimized the rate of change in stem temperature, or by
      applying simple corrections using the DeltaT values for unheated gauges operated
      as blanks. In the field, where dense canopies reduced the radiant energy load on
      stems, temperature corrections were unnecessary, because DeltaT values in
      unheated gauges were near zero.

PMID- 14967713
TI  - Endogenous polyamine concentrations in juvenile, adult and in vitro reinvigorated
      hazel.
AB  - We investigated endogenous polyamine concentrations in leaves from juvenile and
      mature hazel (Corylus avellana L.) shoots, as well as leaves from shoots obtained
      by both forced outgrowth and micropropagation of adult tissues. To determine if
      the observed in vitro reinvigoration was associated with polyamine metabolism, we
      tested the effect of serial subcultures on polyamine concentrations. Polyamines,
      mostly free putrescine, were higher in juvenile tissues. Adult tissues
      micropropagated for 14 subcultures had polyamine concentrations characteristic of
      juvenile tissues. However, with additional subcultures, total polyamine
      concentrations decreased. The putrescine to spermidine plus spermine ratio was
      higher in juvenile and micropropagated tissues than in adult tissues, but
      decreased in micropropagated tissues after 20 subcultures. This ratio may reflect
      a balance between vegetative growth and reproductive processes. Thus, an analysis
      of polyamine concentrations may provide a simple assay for determining the
      juvenility of plant tissues and, hence, their suitability for micropropagation.

PMID- 14967714
TI  - Response of clones of Eucalyptus microtheca to NaCl in vitro.
AB  - We studied the response of nodal segments of Eucalyptus microtheca F.J. Muell. to
      salt stress in a tissue culture system. Three clones of Eucalyptus microtheca
      (37, 42 and 43) were grown in vitro under saline conditions (0-140 mM NaCl) for
      three months. The survival of all three clones decreased with increasing
      concentrations of NaCl in the medium, but the presence of up to 70 mM NaCl
      stimulated rooting in Clones 37 and 42. Shoot elongation of Clone 43 was less
      affected by salt than that of Clones 37 and 42. Leaf growth, expressed as leaf
      length, was stimulated 40% in Clone 42 and 33% in Clone 43, but was progressively
      inhibited up to 27% by 70 mM NaCl in Clone 37. Massive accumulation of Na(+) and
      Cl(-) occurred, especially in Clones 42 and 43 (4000 and 3000 mmol Na(+) kg(DW) (
      1), respectively), as the salinity of the culture solution increased, and this
      was correlated with inhibition of growth. Because of a reduction in the
      accumulation of K(+) with increasing salinity, the K(+)/Na(+) ratio decreased
      from a control value of 4.5 to 0.14 in shoots grown in the presence of 140 mM
      NaCl. The development of techniques for selecting seedlings by monitoring the
      physiology of shoots in vitro instead of testing whole plants in vivo will
      provide a relatively simple method of selection for woody trees.

PMID- 14967715
TI  - 2S Arginine-rich proteins from Pinus pinaster seeds.
AB  - Low molecular weight globulins, which are abundant proteins in the Pinus pinaster
      Ait. megagametophyte, were purified and characterized. They showed a dimeric
      structure formed of one large and one small subunit linked by disulfide bridges.
      They were characterized by a high Arg and Glx content and by a relatively high
      Cys content. A comparison of their characteristics with those of angiosperm 2S
      proteins suggests that there is homology between them.

PMID- 14967716
TI  - Safety and efficacy of enoxaparin compared with unfractionated heparin and oral
      anticoagulants for prevention of thromboembolic complications in cardioversion of
      nonvalvular atrial fibrillation: the Anticoagulation in Cardioversion using
      Enoxaparin (ACE) trial.
AB  - BACKGROUND: Anticoagulation in cardioversion of atrial fibrillation is currently
      performed with unfractionated heparin (UFH) and oral anticoagulants, with or
      without guidance by transesophageal echocardiography (TEE). Low-molecular-weight
      heparins may reduce the risk of bleeding, may obviate the need for intravenous
      access, and do not require frequent anticoagulation monitoring. METHODS AND
      RESULTS: In a randomized, prospective multicenter trial, we compared the safety
      and efficacy of enoxaparin administered subcutaneously with intravenous UFH
      followed by the oral anticoagulant phenprocoumon in 496 patients scheduled for
      cardioversion of atrial fibrillation of >48 hours' and < or =1 year's duration.
      Patients were stratified to cardioversion with (n=431) and without (n=65)
      guidance by TEE. The study aimed to demonstrate noninferiority of enoxaparin
      compared with UFH+phenprocoumon with regard to the incidence of embolic events,
      all-cause death, and major bleeding complications. Secondary end points included
      successful cardioversion, maintenance of sinus rhythm until study end, and minor
      bleeding complications. Of 496 randomized patients, 428 were analyzed per
      protocol. Enoxaparin was noninferior to UFH+phenprocoumon with regard to the
      incidence of the composite primary end point in a per-protocol analysis (7 of 216
      patients versus 12 of 212 patients, respectively; P=0.016) and in an intention-to
      treat analysis (7 of 248 patients versus 12 of 248 patients, respectively;
      P=0.013). There was no significant difference between the 2 groups in the number
      of patients reverted to sinus rhythm. CONCLUSIONS: Enoxaparin is noninferior to
      UFH+phenprocoumon for prevention of ischemic and embolic events, bleeding
      complications, and death in TEE-guided cardioversion of atrial fibrillation. Its
      easier application and more stable anticoagulation may make it the preferred drug
      for initiation of anticoagulation in this setting.

PMID- 14967717
TI  - Asymptotic dental score and prevalent coronary heart disease.
AB  - BACKGROUND: Oral infections have been postulated to produce cytokines that may
      contribute to the pathogenesis of coronary heart disease (CHD). We hypothesized
      that by estimating the combined production of inflammatory mediators attributable
      to several oral pathologies, we might be able to explain CHD with better
      precision. METHODS AND RESULTS: A total of 256 consecutive Finnish cardiac
      patients from Kuopio University Hospital with angiographically confirmed CHD and
      250 age-, gender-, and residence-matched noncardiac patients (controls) were
      recruited. All dental factors expected to generate inflammatory mediators,
      including pericoronitis, dental caries, dentate status, root remnants, and
      gingivitis, were examined, and an asymptotic dental score (ADS) was developed by
      logistic regression analyses with an appropriate weighting scheme according to
      the likelihood ratio. We validated the explanatory ability of ADS by comparing it
      to that of the Total Dental Index and examining whether the ADS was associated
      with known predictors of CHD. A model that included ADS, C-reactive protein, HDL,
      and fibrinogen offered an explanatory ability that equaled or exceeded that of
      the Framingham heart score (C statistic=0.82 versus 0.80). When ADS was removed
      from this model, the C-statistic decreased to 0.77, which indicates that the ADS
      was a significant contributor to the explanatory ability of a logistic model.
      CONCLUSIONS: ADS may be useful as a prescreening tool to promote proactive
      cardiac evaluation among individuals without overt symptoms of CHD. However,
      additional prospective study is needed to validate the use of an oral health
      score as a predictor of incident CHD.

PMID- 14967718
TI  - Impact of microvascular dysfunction on left ventricular remodeling and long-term
      clinical outcome after primary coronary angioplasty for acute myocardial
      infarction.
AB  - BACKGROUND: We hypothesized that preserved microvascular integrity in the area at
      risk would favorably influence left ventricular (LV) remodeling and long-term
      outcome after acute myocardial infarction. METHODS AND RESULTS: Before and after
      successful primary angioplasty (percutaneous transluminal coronary angioplasty
      [PTCA]), 124 patients with acute myocardial infarction underwent intracoronary
      myocardial contrast echo (MCE). An MCE score index (MCESI) was derived by
      averaging the single-segment score (0=not visible, 1=patchy, 2=homogeneous
      contrast effect) within the area at risk. An MCESI > or =1 was considered
      adequate reperfusion. Mean follow-up was 46+/-32 months. After PTCA, 100 patients
      showed adequate reperfusion (no microvascular dysfunction, NoMD), whereas 24 did
      not (MD). MD patients had a higher mean creatine kinase (4153+/-2422 versus
      2743+/-1774 U/L; P=0.002) and baseline wall-motion score index (2.61+/-0.31
      versus 2.25+/-0.42; P<0.001) and a lower baseline ejection fraction (33+/-8%
      versus 40+/-7%; P<0.001). From day 1 on, LV volumes progressively increased in
      the MD patients (n=19) and were larger than those of NoMD patients (n=85) at 6
      months (end-diastolic volume 170+/-55 versus 115+/-29 mL; P<0.001). MCESI was the
      most important independent predictor of LV dilation (OR 0.61, 95% CI 0.52 to
      0.71, P<0.000001). By Cox analysis, MD represented the only predictor of cardiac
      death (OR 0.26, 95% CI 0.09 to 0.72, P=0.010) and combined events (cardiac death,
      reinfarction, and heart failure; OR 0.44, 95% CI 0.23 to 0.85, P=0.014). MD
      patients showed worse survival in terms of cardiac death (P<0.0001) and combined
      events (P<0.0001). CONCLUSIONS: In reperfused acute myocardial infarction, MD
      within the risk area is an important predictor of both LV remodeling and
      unfavorable long-term outcome.

PMID- 14967719
TI  - Simultaneous evaluation of infarct size and cardiac function in intact mice by
      contrast-enhanced cardiac magnetic resonance imaging reveals contractile
      dysfunction in noninfarcted regions early after myocardial infarction.
AB  - BACKGROUND: The objective of this study was to noninvasively determine the
      effects of reperfused myocardial infarction (MI) on regional and global left
      ventricular (LV) function 24 hours after MI in intact mice with contrast-enhanced
      cardiac MRI and a single, gradient-echo pulse sequence. METHODS AND RESULTS:
      Twenty-three mice received baseline MRI scans followed by either 60 minutes of
      coronary occlusion (MI group, n=15) or thoracotomy without occlusion (sham group,
      n=8). Gadolinium-DTPA-enhanced magnetic resonance (MR) images were acquired 24
      hours after surgery. Hearts were then excised for conventional infarct size
      determination via 2,3,5-triphenyl tetrazolium chloride (TTC) staining. In
      addition to infarct size, analysis of the MR images yielded left ventricular (LV)
      mass, LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), LV
      ejection fraction (LVEF), cardiac output, and percent LV wall thickening (%WTh).
      Twenty-four hours after surgery, infarct size was 28.1+/-1.8% of LV mass by MRI
      and 27.5+/-1.7% by TTC (P=NS). Bland-Altman analysis revealed close agreement
      between the results obtained by the 2 methods. MI had little effect on LVEDV but
      caused a 98% increase in LVESV (from 11.3 to 22.4 microL, P<0.05), which resulted
      in a significant reduction in LVEF (from 70% to 37%, P<0.05). Compared with LV
      regional function at baseline, %WTh 24 hours after MI was significantly
      depressed, not only in infarcted myocardium but also in regions remote from the
      infarct zone. In contrast, sham-operated mice showed a small but significant
      increase in %WTh 24 hours after surgery (P<0.05). CONCLUSIONS: MRI can accurately
      assess both infarct size and cardiac function in intact mice early after large,
      reperfused MI, revealing the existence of contractile dysfunction in noninfarcted
      regions of the heart.

PMID- 14967720
TI  - Protective effects of endogenous adrenomedullin on cardiac hypertrophy, fibrosis,
      and renal damage.
AB  - BACKGROUND: Adrenomedullin (AM) is a novel vasodilating peptide thought to have
      important effects on cardiovascular function. The aim of this study was to assess
      the activity of endogenous AM in the cardiovascular system using AM knockout
      mice. METHODS AND RESULTS: Mice heterozygous for an AM-null mutation (AM+/-) and
      their wild-type littermates were subjected to aortic constriction or angiotensin
      II (Ang II) infusion. The resultant cardiovascular stress led to increases in
      heart weight/body weight ratios, left ventricular wall thickness, and
      perivascular fibrosis, as well as expression of genes encoding angiotensinogen,
      ACE, transforming growth factor-beta, collagen type I, brain natriuretic peptide,
      and c-fos. In addition, renal damage characterized by decreased creatinine
      clearance with glomerular sclerosis was noted. In all cases, the effects were
      significantly more pronounced in AM+/- mice. Hearts from adult mice subjected to
      aortic constriction showed enhanced extracellular signal-regulated kinase (ERK)
      activation, as did cardiac myocytes from neonates treated acutely with Ang II.
      Again the effect was more pronounced in AM+/- mice, which showed increases in
      cardiac myocyte size, protein synthesis, and fibroblast proliferation. ERK
      activation was suppressed by protein kinase C inhibition to a greater degree in
      AM+/- myocytes. In addition, treatment of cardiac myocytes with recombinant AM
      suppressed Ang II-induced ERK activation via a protein kinase A-dependent
      pathway. CONCLUSIONS: Endogenous AM exerts a protective effect against stress
      induced cardiac hypertrophy via protein kinase C- and protein kinase A-dependent
      regulation of ERK activation. AM may thus represent a useful new tool for the
      treatment of cardiovascular disease.

PMID- 14967721
TI  - Mechanisms of myocardial capture and temporal excitable gap during spiral wave
      reentry in a bidomain model.
AB  - BACKGROUND: Recent studies have demonstrated that regional capture during cardiac
      fibrillation is associated with an elevated capture threshold. It is typically
      assumed that the temporal excitable gap (capture window) during fibrillation
      reflects the size of the spatial excitable gap (excitable tissue between
      fibrillation waves). Because capture threshold is high, virtual electrode
      polarization is expected to be involved in the process. However, little is known
      about the underlying mechanisms of myocardial capture during fibrillation.
      METHODS AND RESULTS: To clarify these issues, we conducted altogether 3168
      simulations of single spiral wave capture in a bidomain sheet. Unipolar stimuli
      of strengths 4, 8, 16, and 24 mA and 2-ms duration were delivered at 99 locations
      in the sheet. We found that cathode-break rather than cathode-make excitation was
      the dominant mechanism of myocardial capture. When the stimulation site was
      located diagonally with respect to the core (upper left or lower right if the
      spiral wave rotates counterclockwise), the cathode-break excitation easily
      invaded the spatial excitable gap and resulted in a successful capture as a
      result of the formation of virtual anodes in the direction of the myocardial
      fibers. Thus, the spatial distribution of the temporal excitable gap did not
      reflect the spatial excitable gap. CONCLUSIONS: The areas exhibiting wide
      temporal excitable gaps were areas in which the cathode-break excitation wave
      fronts easily invaded the spatial excitable gap via the virtual anodes. This
      study provides mechanistic insight into myocardial capture.

PMID- 14967722
TI  - Mechanisms of exercise intolerance: insights from tissue Doppler imaging.
AB  - BACKGROUND: A decreased ratio of early to late diastolic mitral inflow velocities
      (E/A <1.0) reflects slowing of left ventricular (LV) relaxation. This finding is
      widely believed to indicate significant diastolic dysfunction. However, E/A <1.0
      is common during normal aging and often is not associated with symptoms of heart
      failure. We asked (1) whether slowed LV relaxation is associated with exercise
      intolerance and (2) whether tissue Doppler imaging of the early diastolic mitral
      annular velocity (Ea) is helpful in understanding mechanisms of exercise
      intolerance. METHODS AND RESULTS: Patients (n=121) underwent echocardiography
      before maximal exercise testing. Fifty-nine subjects had E/A <1.0, and 36
      subjects had E/Ea > or =10. Exercise capacity was similar in the population with
      a normal mitral inflow pattern and those with a slow relaxation pattern when E/Ea
      was <10. In contrast, the subjects with slow relaxation and E/Ea > or =10 had
      reduced exercise tolerance. Of all the echo and clinical parameters assessed,
      E/Ea had the best correlation with exercise capacity (r=-0.684, P<0.001) and was
      the strongest independent predictor of exercise capacity < or =7 METs by
      multivariate analysis (prevalence-corrected odds ratio=12.6, P<0.001). E/Ea
      continued to be strongly associated with exercise capacity in all age groups and
      in those with preserved or reduced systolic function. CONCLUSIONS: Of the
      subjects with slow LV relaxation, only those with E/Ea > or =10 have objective
      evidence of reduced exercise tolerance. These data suggest that elevated LV
      filling pressures rather than slow relaxation per se reduce exercise capacity.

PMID- 14967723
TI  - Reoxygenation of hypoxic coronary smooth muscle cells amplifies growth-retarding
      effects of ionizing irradiation.
AB  - BACKGROUND: Hypoxic human coronary smooth muscle cells (HCSMCs) are possible
      targets for brachytherapy to prevent restenosis after percutaneous transluminal
      coronary angiography. It is unclear whether growth kinetics and gene expression
      of these cells undergoing gamma-irradiation are changed by reoxygenation. METHODS
      AND RESULTS: Hypoxic (H) and hypoxia-reoxygenated (H-R) HCSMCs were irradiated
      with gamma-radiation at single doses of 4, 8, and 16 Gy using a 60Co-source.
      Vascular endothelial growth factor gene expression of HCSMCs was dramatically
      suppressed in H-R versus H cells independent of the radiation dose (15+/-7%
      versus 2183+/-2023%, P<0.01, H-R versus H cells). An oxygen enhancement ratio of
      1.8 was calculated after irradiation from the retarded growth of H-R versus
      hypoxic HCSMCs. Production of reactive oxygen species by HCSMCs after irradiation
      increased by 15+/-2% in H-R cells versus 7+/-1% in H cells (P<0.05). CONCLUSIONS:
      Reoxygenation of hypoxic HCSMCs markedly amplifies growth-retarding effects of
      ionizing irradiation. On the basis of these findings, oxygenating
      radiosensitizers should be analyzed with regard to suitability for coronary
      brachytherapy to prevent restenosis.

PMID- 14967724
TI  - Remnant lipoprotein particles induce apoptosis in endothelial cells by NAD(P)H
      oxidase-mediated production of superoxide and cytokines via lectin-like oxidized
      low-density lipoprotein receptor-1 activation: prevention by cilostazol.
AB  - BACKGROUND: Remnant lipoprotein particles (RLPs), products of lipolytic
      degradation of triglyceride-rich lipoprotein derived from VLDL, exert
      atherogenesis. In this study, we observed how RLPs induced cytotoxicity in human
      umbilical vein endothelial cells (HUVECs) and cilostazol prevented cell death.
      METHODS AND RESULTS: RLPs were isolated from the plasma of hyperlipidemic
      patients by use of an immunoaffinity gel mixture of anti-apolipoprotein A-1 and
      anti-apolipoprotein B-100 monoclonal antibodies. RLPs (50 microg/mL)
      significantly increased superoxide formation in HUVECs associated with elevated
      gp91phox mRNA and protein expression and Rac1 translocation, accompanied by
      increased production of tumor necrosis factor (TNF)-alpha and interleukin-1beta,
      DNA fragmentation, and cell death. Cilostazol (1 to 100 micromol/L) significantly
      suppressed not only NAD(P)H oxidase-dependent superoxide production but also TNF
      alpha and interleukin-1beta release and restored viability. RLPs activated a
      lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), which was not
      inhibited by cilostazol. Treatment of HUVECs with monoclonal antibody for LOX-1
      attenuated RLP-mediated production of superoxide, TNF-alpha, and interleukin
      1beta and DNA fragmentation. CONCLUSIONS: RLPs stimulated NAD(P)H oxidase
      dependent superoxide formation and induction of cytokines in HUVECs via
      activation of LOX-1, consequently leading to reduction in cell viability with DNA
      fragmentation, and cilostazol exerts a cell-protective effect by suppressing
      these variables.

PMID- 14967725
TI  - Slow conduction and enhanced anisotropy increase the propensity for ventricular
      tachyarrhythmias in adult mice with induced deletion of connexin43.
AB  - BACKGROUND: Connexin 43 (Cx43) is a major determinant of conduction in the
      ventricular working myocardium of mammals. We investigated the effect of
      decreased Cx43 expression on conduction velocity and arrhythmogenesis using adult
      mice with inducible deletion of Cx43. METHODS AND RESULTS: Cx43Cre-ER(T)/+ mice,
      in which 1 coding region of the Cx43 gene was replaced by Cre-ER(T), were mated
      to Cx43fl/fl mice, generating Cx43Cre-ER(T)/fl mice. Application of 4
      hydroxytamoxifen (4-OHT) induced Cre-ER(T)-mediated deletion of the floxed Cx43
      allele. Epicardial ventricular mapping using a 13x19 multiterminal electrode grid
      (300-microm spacing) was performed on Langendorff-perfused hearts from Cx43fl/fl
      plus carrier (n=10), Cx43fl/fl plus 4-OHT (n=10), Cx43 Cre-ER(T)/fl plus carrier
      (n=9), and Cx43Cre-ER(T)/fl plus 4-OHT (n=10). Cx43 protein amount in group 3
      hearts was decreased by 50% compared with group 1. 4-OHT did not affect cardiac
      protein amounts in group 2 but decreased Cx43 expression up to 95% in group 4
      compared with group 3. Epicardial activation of both left ventricle (LV) and
      right ventricle (RV) during sinus rhythm was similar in all groups. Conduction
      velocity (CV) changed only in group 4 animals. For RV (LV), longitudinal CV
      decreased from 38 (35) to 31.6 (33.6) and transverse CV from 24.4 (16.8) to 10.1
      (11.3) cm/s. Dispersion of conduction in RV (LV) was increased by 91% (38%).
      Programmed stimulation resulted in ventricular arrhythmias in group 4 (7 of 10
      mice) but never in groups 1 through 3. CONCLUSIONS: Heterozygous expression of
      Cx43 did not affect ventricular conduction velocity. Up to 95% decrease of Cx43
      protein in 4-OHT-treated Cx43(Cre-ER(T)/fl) mice reduced conduction velocity and
      increased dispersion of conduction and propensity for ventricular arrhythmias.

PMID- 14967726
TI  - Altered calcium handling is critically involved in the cardiotoxic effects of
      chronic beta-adrenergic stimulation.
AB  - BACKGROUND: Chronic adrenergic stimulation leads to cardiac hypertrophy and heart
      failure in experimental models and contributes to the progression of heart
      failure in humans. The pathways mediating the detrimental effects of chronic beta
      adrenergic stimulation are only partly understood. We investigated whether
      genetic modification of calcium handling through deletion of phospholamban in
      mice would affect the development of heart failure in mice with transgenic
      overexpression of the beta1-adrenergic receptor. METHODS AND RESULTS: We crossed
      beta1-adrenergic receptor transgenic (beta1TG) mice with mice homozygous for a
      targeted deletion of the phospholamban gene (PLB-/-). Phospholamban ablation
      dramatically enhanced survival of beta1TG mice. The decrease of left ventricular
      contractility typically observed in beta1TG mice was reverted back to normal by
      phospholamban ablation. Cardiac hypertrophy and fibrosis were significantly
      inhibited in beta1TG/PLB-/- mice compared with beta1TG mice, and the heart
      failure-specific gene expression pattern was normalized. Analysis of
      intracellular calcium transients revealed increased diastolic calcium levels and
      decreased rate constants of diastolic calcium decline in beta1TG mice. In
      beta1TG/PLB-/- mice, diastolic calcium concentration was normal and rate
      constants of diastolic calcium decline were greater than in wild-type mice.
      CONCLUSIONS: We conclude that modification of abnormal calcium handling in
      beta1TG mice through ablation of phospholamban resulted in a rescue of
      functional, morphological, and molecular characteristics of heart failure in
      beta1-adrenergic receptor-transgenic mice. These results imply altered calcium
      handling as critical for the detrimental effects of beta1-adrenergic signaling.

PMID- 14967727
TI  - Usefulness of B-type natriuretic peptide assay in the assessment of symptomatic
      state in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) has a diverse clinical spectrum
      that often includes progressive heart failure symptoms and disability. Assessment
      of symptom severity may be highly subjective, encumbered by the heterogeneous
      clinical presentation. Plasma B-type natriuretic peptide (BNP) has been used
      widely as an objective marker for heart failure severity and outcome,
      predominantly in coronary heart disease with ventricular dilatation and systolic
      dysfunction. METHODS AND RESULTS: We prospectively assessed plasma BNP as a
      quantitative clinical marker of heart failure severity in 107 consecutive HCM
      patients. BNP showed a statistically significant relationship to magnitude of
      functional limitation, assessed by New York Heart Association (NYHA) functional
      class: I, 136+/-159 pg/mL; II, 338+/-439 pg/mL; and III/IV, 481+/-334 pg/mL
      (P<0.001). Multivariable analysis showed that BNP was independently related to
      NYHA class as well as age and left ventricular wall thickness (each with a value
      of P=0.0001). BNP > or =200 pg/mL was the most reliable predictor of heart
      failure symptoms, with positive and negative predictive values of 63% and 79%,
      respectively. BNP power in distinguishing patients with or without heart failure
      symptoms was less than that for differentiating between no (or only mild) and
      severe symptoms (area under receiver operating characteristic curve=0.75 and
      0.83, respectively). CONCLUSIONS: Plasma BNP is independently related to the
      presence and magnitude of heart failure symptoms in patients with HCM. As a
      clinical marker for heart failure, BNP is limited by considerable overlap in
      values between categories of heart failure severity as well as confounding
      variables of left ventricular wall thickness and age.

PMID- 14967728
TI  - Mortality in patients after a recent myocardial infarction: a randomized, placebo
      controlled trial of azimilide using heart rate variability for risk
      stratification.
AB  - BACKGROUND: Depressed left ventricular function (LVF) and low heart rate
      variability (HRV) identify patients at risk of increased mortality after
      myocardial infarction (MI). Azimilide, a novel class III antiarrhythmic drug, was
      investigated for its effects on mortality in patients with depressed LVF after
      recent MI and in a subpopulation of patients with low HRV. METHODS AND RESULTS: A
      total of 3717 post-MI patients with depressed LVF were enrolled in this
      randomized, placebo-controlled, double-blind study of azimilide 100 mg on all
      cause mortality. Placebo patients with low HRV had a significantly higher 1-year
      mortality than those with high HRV (>20 U; 15% versus 9.5%, P<0.0005) despite
      nearly identical ejection fractions. No significant differences were observed
      between the 100-mg azimilide and placebo groups for all-cause mortality in either
      the "at-risk" patients identified by depressed LVF (12% versus 12%) or the
      subpopulation of "high-risk" patients identified by low HRV (14% versus 15%) or
      for total cardiac or arrhythmic mortality. Significantly fewer patients receiving
      azimilide developed atrial fibrillation than did patients receiving placebo (0.5%
      versus 1.2%, P<0.04). The incidences of torsade de pointes and severe neutropenia
      (absolute neutrophil count < or =500 cells/microL) were slightly higher in the
      azimilide group than in the placebo group (0.3% versus 0.1% for torsade de
      pointes and 0.9% versus 0.2% for severe neutropenia). CONCLUSIONS: Azimilide did
      not improve or worsen the mortality of patients after MI. Low HRV independently
      identified a subpopulation at high risk of mortality.

PMID- 14967729
TI  - Predictors of outcome after alcohol septal ablation therapy in patients with
      hypertrophic obstructive cardiomyopathy.
AB  - BACKGROUND: Alcohol septal ablation (ASA) therapy results in clinical and
      hemodynamic improvement in patients with hypertrophic obstructive cardiomyopathy.
      However, a subset remains symptomatic afterward, requiring additional procedures.
      We sought to examine the determinants of an unsatisfactory outcome, defined as
      unchanged symptoms with <50% reduction of baseline left ventricular outflow tract
      (LVOT) gradient. METHODS AND RESULTS: Of 173 consecutive hypertrophic obstructive
      cardiomyopathy patients who underwent ASA, 39 had an unsatisfactory outcome after
      the first procedure. Patients with an unsatisfactory outcome had a higher
      baseline LVOT gradient, fewer septal arteries injected with ethanol, lower peak
      creatine kinase (CK), smaller septal area opacified by contrast echocardiography,
      and higher residual gradient in the catheterization laboratory after ASA (all
      P<0.05). Symptoms, septal thickness, mitral regurgitation severity, and
      ventricular function were not determinants of outcome. On multiple logistic
      regression, LVOT gradient reduction after ASA in the catheterization laboratory
      to > or =25 mm Hg (OR, 5.5; P=0.01) and peak CK <1300 U/L (OR, 2.5; P=0.04) were
      the independent predictors of an unsatisfactory outcome. CONCLUSIONS: The
      residual LVOT gradient in the catheterization laboratory and peak CK leak after
      ASA are the independent predictors of ASA outcome.

PMID- 14967730
TI  - C-reactive protein upregulates complement-inhibitory factors in endothelial
      cells.
AB  - BACKGROUND: Because complement-mediated vascular injury participates in
      atherosclerosis and C-reactive protein (CRP) can activate the complement cascade,
      we sought to determine whether CRP affects the expression of the protective
      complement-inhibitory factors on the cell surface of endothelial cells (ECs).
      METHODS AND RESULTS: Human coronary artery or human saphenous vein ECs were
      incubated with CRP (0 to 100 microg/mL, 0 to 72 hours), and the expression of the
      complement-inhibitory proteins decay-accelerating factor (DAF), membrane cofactor
      protein (CD46), and CD59 were measured by flow cytometry. Incubation with CRP
      resulted in a significant increase in the expression of all 3 proteins. CRP
      induced upregulation of DAF required increased steady-state mRNA and de novo
      protein synthesis. The increased expression of complement-inhibitory proteins was
      functionally effective, resulting in significant reduction of complement-mediated
      lysis of antibody-coated human saphenous vein ECs. CONCLUSIONS: These
      observations provide evidence for a possible protective role for CRP in
      atherogenesis.

PMID- 14967731
TI  - Magnetic resonance imaging identifies the fibrous cap in atherosclerotic
      abdominal aortic aneurysm.
AB  - BACKGROUND: MRI can distinguish components of atherosclerotic plaque. We
      hypothesized that contrast enhancement with gadolinium-DTPA (Gd-DTPA) could aid
      in the differentiation of plaque components in abdominal aortic aneurysm (AAA).
      METHODS AND RESULTS: Twenty-three patients (19 males, age 70+/-8 years) with AAA
      underwent MRI on a 1.5-T clinical scanner 3+/-3 days before surgical grafting. T1
      and T2-weighted (W) black blood spin echo imaging was performed in 1 axial
      slice, and the T1-W imaging was repeated after a Gd-DTPA-enhanced 3D magnetic
      resonance angiogram. A section of the aorta at the site of imaging was resected
      at surgery for histopathologic examination of tissue components and inflammatory
      cells. Signal-to-noise and contrast-to-noise ratios (CNR) were measured in
      visualized plaque components from multispectral MRI, and percent enhancement
      after contrast on T1-W imaging was calculated. The kappa value for agreement
      between pathology and MRI for the number of tissue components was 0.785. T2-W
      imaging identified thrombus as regions of high signal and lipid core as low
      signal, with a CNR of 6.43+/-3.41. Nine patients had a fibrous cap
      pathologically, which was visualized as a discrete area of uniform increased
      signal on T2-W imaging with a CNR of 4.52+/-1.93 compared with lipid core. Within
      the cap, the percent enhancement after Gd-DTPA on T1-W imaging was 91+/-63%.
      CONCLUSIONS: Higher signal on T2-W MRI identifies the fibrous cap and thrombus
      within AAA. Contrast enhancement improves delineation of the fibrous cap. The
      addition of contrast to MRI plaque imaging may enhance identification of
      vulnerable plaque.

PMID- 14967732
TI  - Incidence, mechanism, predictors, and long-term prognosis of late stent
      malapposition after bare-metal stent implantation.
AB  - BACKGROUND: Predictors and long-term prognosis of late stent malapposition (LSM)
      after bare-metal stent (BMS) implantation are unknown. METHODS AND RESULTS: We
      evaluated the incidence, mechanisms, predictors, and long-term prognosis of LSM
      after BMS implantation in 881 patients (992 native lesions) in whom intravascular
      ultrasound was performed at index and 6-month follow-up. LSM was defined as a
      separation of stent struts from the intimal surface of the arterial wall that was
      not presented at stent implantation. LSM occurred in 54 patients with 54 lesions
      (5.4% overall); the incidence was 10.3% (9 of 87) after directional coronary
      atherectomy (DCA) before stenting and 11.5% (11 of 96) after primary stenting in
      acute myocardial infarction (P=0.031 and P=0.007, respectively, versus elective
      stenting with conventional balloon pre-dilation, 4.3% [30 of 692]). There was an
      increase of external elastic membrane area (18.9+/-3.9 to 24.5+/-5.1 mm2,
      P<0.001) that was greater than the increase in plaque area (9.6+/-3.0 to 11.4+/
      2.9 mm2, P<0.001). Independent predictors of LSM were primary stenting in acute
      myocardial infarction (P=0.023, OR=2.55, 95% CI=1.14 to 5.69) and DCA before
      stenting (P=0.025, OR=3.02, 95% CI=1.15 to 7.96). There were no significant
      differences in major adverse cardiac events between LSM and non-LSM groups during
      mean 3-year follow-up (1.9% versus 1.8%, respectively, P=NS). CONCLUSIONS: LSM
      occurs in approximately 5% after BMS implantation. The predictors of LSM are
      primary stenting in acute myocardial infarction and DCA before stenting. Compared
      with complete stent apposition at follow-up, LSM after BMS implantation is not
      associated with any major adverse cardiac events during a mean 3-year follow-up
      after detection of LSM.

PMID- 14967733
TI  - Leukocyte-targeted myocardial contrast echocardiography can assess the degree of
      acute allograft rejection in a rat cardiac transplantation model.
AB  - BACKGROUND: Repetitive endomyocardial biopsies are necessary to monitor the
      effects of immunosuppressants after cardiac transplantation. Contrast ultrasound
      with microbubble targeting of leukocytes detects acute leukocyte infiltration. We
      examined whether leukocyte-targeted myocardial contrast echocardiography (MCE)
      could provide for the quantitative assessment of acute cardiac rejection. METHODS
      AND RESULTS: Hearts from Brown Norway rats or Lewis rats were transplanted into
      other Brown Norway rats. Isografts and groups of allografts either untreated or
      treated with cyclosporin A (CsA) at a low dose (3 mg x kg(-1) x d(-1)) or high
      dose (10 mg x kg(-1) x d(-1)) from 3 days before transplantation were compared at
      posttransplantation day 3. Echocardiography-derived left ventricular wall
      thickening was comparable among the 4 groups. Myocardial blood flow assessed with
      MCE, relating pulsing intervals with signal intensity (SI), was slightly
      decreased only in untreated allografts. However, myocardial SI (in gray levels)
      obtained after a 10-minute period allowing microbubble-leukocyte interactions
      after contrast injection exhibited a clear gradient in these groups (12+/-2 in
      untreated allografts, 9+/-5 in allografts treated with low-dose CsA, 6+/-3 in
      allografts treated with high-dose CsA, and 2+/-1 in isografts, P<0.001). The
      pattern of difference in SI among the groups agreed well with that in ED-1
      positive cell (macrophage) count (25+/-7, 12+/-4, 5+/-3, and 1+/-0 cells per high
      power field, respectively, P<0.001), which correlated with CD3-positive cell (T
      lymphocyte) count (33+/-5, 22+/-5, 9+/-4, and 1+/-0 cells per high-power field,
      respectively, P<0.001). CONCLUSIONS: Leukocyte-targeted MCE can noninvasively
      assess the degree of rejection in transplanted hearts by directly revealing the
      magnitude of intramyocardial infiltration of macrophages and T lymphocytes.

PMID- 14967734
TI  - Pressure-induced matrix metalloproteinase-9 contributes to early hypertensive
      remodeling.
AB  - BACKGROUND: High blood pressure causes a change in vascular wall structure
      involving altered extracellular matrix composition, but how this process occurs
      is not fully understood. METHODS AND RESULTS: Using mouse carotid arteries
      maintained in organ culture for 3 days, we detected increased gelatin zymographic
      activity of matrix metalloproteinase (MMP)-2 (168+/-13%, P<0.05) in vessels kept
      at low intraluminal pressure (10 mm Hg) compared with vessels at 80 mm Hg (100%),
      whereas in vessels maintained at high pressure (150 mm Hg), both MMP-2 and MMP-9
      activity was induced (182+/-32%, P<0.05, and 194+/-21%, P<0.01, respectively).
      MMPs were detected in endothelial and smooth muscle cells by immunohistochemistry
      and in situ gelatin zymography. In vessels at 150 mm Hg, MMP activation was
      associated with a shift in the pressure-diameter curve toward greater
      distensibility (P<0.01) compared with vessels at 80 mm Hg. However,
      distensibility was not altered in vessels at 10 mm Hg, in which only activated
      MMP-2 was detected. The role of MMPs in high pressure-induced vessel
      distensibility was confirmed by use of the MMP inhibitor FN-439, which prevented
      the shift in the pressure-diameter relationship. Furthermore, in carotid arteries
      from MMP-9-deficient mice, the pressure-dependent increase in MMP-2 and in situ
      gelatinolytic activity were maintained, but the upward shift in the pressure
      diameter curve was abolished. CONCLUSIONS: MMP-9 seems to play a key role in the
      early stages of hypertensive vascular remodeling.

PMID- 14967735
TI  - Adenoviral catheter-mediated intramyocardial gene transfer using the mature form
      of vascular endothelial growth factor-D induces transmural angiogenesis in
      porcine heart.
AB  - BACKGROUND: It is unclear what is the most efficient vector and growth factor for
      induction of therapeutic vascular growth in the heart. Furthermore, the
      histological nature of angiogenesis and potential side effects caused by
      different vascular endothelial growth factors (VEGFs) in myocardium have not been
      documented. METHODS AND RESULTS: Adenoviruses (Ad) at 2 doses (2x10(11) and
      2x10(12) viral particles) or naked plasmids (1 mg) encoding LacZ control, VEGF
      A165, or the mature, soluble form of VEGF-D (VEGF-D(DeltaNDeltaC)) were injected
      intramyocardially with the NOGA catheter system into domestic pigs. AdVEGF
      D(DeltaNDeltaC) gene transfer (GT) induced a dose-dependent myocardial protein
      production, as measured by ELISA, resulting in an efficient angiogenic effect 6
      days after the injections. Also, AdVEGF-A165 produced high gene transfer
      efficacy, as demonstrated with immunohistochemistry, leading to prominent
      angiogenesis effects. Despite the catheter-mediated approach, angiogenesis
      induced by both AdVEGFs was transmural, with maximal effects in the epicardium.
      Histologically, strongly enlarged alpha-smooth muscle actin-positive microvessels
      involving abundant cell proliferation were found in the transduced regions,
      whereas microvessel density did not change. Myocardial contrast echocardiography
      and microspheres showed marked increases in perfusion in the transduced areas.
      VEGF-D(DeltaNDeltaC) but not matrix-bound VEGF-A165 was detected in plasma after
      adenoviral GT. A modified Miles assay demonstrated myocardial edema resulting in
      pericardial effusion with the higher AdVEGF doses. All effects returned to
      baseline by 3 weeks. Naked plasmid-mediated GT did not induce detectable protein
      production or vascular effects. CONCLUSIONS: Like AdVEGF-A165, AdVEGF
      D(DeltaNDeltaC) GT using the NOGA system produces efficient transmural
      angiogenesis and increases myocardial perfusion. AdVEGF-D(DeltaNDeltaC) could be
      useful for the induction of therapeutic vascular growth in the heart.

PMID- 14967736
TI  - Endothelin-1-induced cardiac hypertrophy is inhibited by activation of peroxisome
      proliferator-activated receptor-alpha partly via blockade of c-Jun NH2-terminal
      kinase pathway.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a
      lipid-activated nuclear receptor that negatively regulates the vascular
      inflammatory gene response by interacting with transcription factors, nuclear
      factor-kappaB, and AP-1. However, the roles of PPAR-alpha activators in
      endothelin (ET)-1-induced cardiac hypertrophy are not yet known. METHODS AND
      RESULTS: First, in cultured neonatal rat cardiomyocytes, a PPAR-alpha activator,
      fenofibrate (10 micromol/L), and PPAR-alpha overexpression markedly inhibited the
      ET-1-induced increase in protein synthesis. Second, fenofibrate markedly
      inhibited ET-1-induced increase in c-Jun gene expression and phosphorylation of c
      Jun and JNK. These results suggest that this PPAR-alpha activator interferes with
      the formation and activation of AP-1 protein induced by ET-1 in cardiomyocytes.
      Third, fenofibrate significantly inhibited the increase of ET-1 mRNA level by ET
      1, which was also confirmed by luciferase assay. Electrophoretic mobility shift
      assay revealed that fenofibrate significantly decreased the ET-1-stimulated or
      phorbol 12-myristate 13-acetate-stimulated AP-1 DNA binding activity, and the
      nuclear extract probe complex was supershifted by anti-c-Jun antibody. Fourth, 24
      hours after aortic banding (AB) operation, fenofibrate treatment significantly
      inhibited left ventricular hypertrophy and hypertrophy-related gene expression
      pattern (ET-1, brain natriuretic peptide, and beta-myosin heavy chain mRNA) in AB
      rats. CONCLUSIONS: These results suggest that PPAR-alpha activation interferes
      with the signaling pathway of ET-1-induced cardiac hypertrophy through negative
      regulation of AP-1 binding activity, partly via inhibition of the JNK pathway in
      cultured cardiomyocytes. We also revealed that fenofibrate treatment inhibited
      left ventricle hypertrophy and phenotypic changes in cardiac gene expression in
      AB rats in vivo.

PMID- 14967737
TI  - Contribution of vanilloid receptors to the overt nociception induced by B2 kinin
      receptor activation in mice.
AB  - 1. The vanilloid receptor (TRPV1) is viewed as a molecular integrator of several
      nociceptive stimuli. In the present study, we have investigated the role played
      by TRPV1 in the nociceptive response induced by the peripheral activation of
      kinin B(2) receptor in mice. 2. The intraplantar (i.pl.) administration of
      bradykinin (BK) and the selective B(2) agonist Tyr(8)-BK, or the vanilloid
      agonists resiniferatoxin and capsaicin, into the mouse paw induced a dose-related
      overt nociception of short duration. The B(2) receptor antagonist Hoe 140
      inhibited BK-induced, but not capsaicin-induced, nociceptive response. On the
      other hand, the TRPV1 antagonist capsazepine inhibited both capsaicin- and BK
      mediated nociception. 3. Repeated injections of BK or capsaicin produced
      desensitization to their nociceptive response. Capsaicin desensitization greatly
      reduced BK-induced nociception, but in contrast, the desensitization to BK
      increased the capsaicin response. 4. Administration of low doses of capsaicin or
      acidified saline did not produce nociception when administered alone, but caused
      a pronounced effect when administered in association with a subthreshold dose of
      BK. Moreover, the degeneration of the subset of primary afferent fibers,
      sensitive to capsaicin, abolished both capsaicin- and BK-induced nociception. 5.
      The inhibition of phospholipase C (PLC), protein kinase C or phospholipase A(2)
      markedly decreased the nociception caused by BK, but not that of capsaicin. BK
      administration increased leukotriene B(4) levels in the injected paw. Likewise,
      BK-induced overt nociception was decreased by lipoxygenase (LOX) inhibition. 6.
      These results demonstrate that BK produces overt nociception mediated by TRPV1
      receptor stimulation, via PLC pathway activation and LOX product formation.

PMID- 14967738
TI  - General anesthetic octanol and related compounds activate wild-type and delF508
      cystic fibrosis chloride channels.
AB  - 1. Cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is
      defective during cystic fibrosis (CF). Activators of the CFTR Cl(-) channel may
      be useful for therapy of CF. Here, we demonstrate that a range of general
      anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate
      the Cl(-) channel activity of wild-type CFTR and delF508-CFTR mutant. 2. The
      effects of n-alkanols like octanol on CFTR activity were measured by iodide
      ((125)I) efflux and patch-clamp techniques on three distinct cellular models:
      (1). CFTR-expressing Chinese hamster ovary cells, (2). human airway Calu-3
      epithelial cells and (3). human airway JME/CF15 epithelial cells which express
      the delF508-CFTR mutant. 3. Our data show for the first time that n-alkanols
      activate both wild-type CFTR and delF508-CFTR mutant. Octanol stimulated (125)I
      efflux in a dose-dependent manner in CFTR-expressing cells (wild-type and
      delF508) but not in cell lines lacking CFTR. (125)I efflux and Cl(-) currents
      induced by octanol were blocked by glibenclamide but insensitive to 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid, as expected for a CFTR Cl(-)
      current. 4. CFTR activation by octanol was neither due to cell-to-cell uncoupling
      properties of octanol nor to an intracellular cAMP increase. CFTR activation by
      octanol requires phosphorylation by protein kinase-A (PKA) since it was prevented
      by H-89, a PKA inhibitor. 5. n-Alkanols chain length was an important determinant
      for channel activation, with rank order of potencies: 1-heptanol<1-octanol<2
      octanol<1-decanol. Our findings may be of valuable interest for developing novel
      therapeutic strategies for CF.

PMID- 14967739
TI  - NPY presynaptic actions are reduced in the hypothalamic mpPVN of obese (fa/fa),
      but not lean, Zucker rats in vitro.
AB  - 1. Neuropeptide Y (NPY) profoundly enhances feeding when injected
      intracerebroventricularly, or directly into hypothalamic nuclei, such as the
      paraventricular nucleus (PVN). Paradoxically, NPY has a reduced action on feeding
      in obese Zucker rats relative to lean Zucker rats, although the obese rats have
      much higher levels of hypothalamic NPY expression. GABAergic inputs to a
      subpopulation of medial parvocellular PVN (mpPVN) neurons are sensitive to NPY.
      Here, we tested the hypothesis that the blunted eating response to NPY observed
      in obese Zucker rats will be reflected in a reduced NPY action at mpPVN GABAergic
      synapses. 2. 'Blind' whole-cell patch-clamp recordings made from mpPVN neurons in
      acute brain slices of lean and obese Zucker rats revealed GABAergic inhibitory
      postsynaptic currents (IPSC) responses which were inhibited by NPY. While the
      maximum response in the obese Zucker rats was significantly less than in lean
      Zucker or Sprague-Dawley rats, there was no difference in the EC(50). 3.
      Experiments using blocking concentrations of Y(1)- or Y(5)-receptor antagonists
      revealed no differences between lean and obese Zucker rats in the contributions
      of either of these receptors to the total NPY response in mpPVN. 4. NPY is less
      effective at the mpPVN GABA synapse in obese than in lean Zucker rats. This is
      not associated with a change in the proportion of Y(1) or Y(5) receptors
      mediating the NPY response, and is consistent with the downregulation of NPY
      receptors or a reduction in receptor-effector coupling, and with the reduced
      sensitivity of obese rats to NPY.

PMID- 14967740
TI  - Truth and consequences of the new duty requirements: a resident's perspective.

PMID- 14967741
TI  - Quality of life and sun-protective behavior in patients with skin cancer.
AB  - OBJECTIVES: To determine whether change occurred in the general quality of life
      (QOL) of nonmelanoma skin cancer (NMSC) patients following surgery, to identify
      variables associated with patients' change in QOL, and to assess the impact of
      the disease and treatment on sun-protective behaviors and cigarette smoking.
      DESIGN: Longitudinal prospective study of 121 consecutive patients referred to a
      dermatologic Mohs surgery clinic with NMSC of the head and neck. INTERVENTIONS:
      Quality-of-life, smoking habit, and sun-protective behavior assessments were
      performed before treatment (N=121) and after surgical treatment at 1 (n=105) and
      4 (n=101) months. Quality-of-life measures included the Medical Outcomes Study 36
      Item Short-Form Health Survey and the Functional Assessment of Cancer Therapy
      General. RESULTS: Overall, general QOL measures demonstrated little change over
      time. Only the mental (Medical Outcomes Study 36-Item Short-Form Health Survey)
      and emotional (Functional Assessment of Cancer Therapy-General) domains of QOL
      showed statistically significant change over time. A 2-way interaction showing
      effects for age and time on emotional well-being was modified by a 3-way
      interaction that depended on employment status. Emotional well-being scores for
      younger employed NMSC patients increased over time compared with scores among
      younger unemployed patients. In addition, many patients adopted greater use of
      sun-protective behaviors at 4 months following surgery. No change in cigarette
      smoking status was evidenced. CONCLUSIONS: Use of sun-protective behaviors
      increases after treatment. General QOL instruments demonstrate little change
      following treatment of NMSC. Although the associations are modest, improvements
      in emotional and mental health well-being following treatment of NMSC were
      demonstrated, especially for those younger than 65 years and employed. A disease
      specific instrument may be necessary to further study this disease process.

PMID- 14967742
TI  - The impact of neck dissection on health-related quality of life.
AB  - OBJECTIVE: To compare health-related quality of life in patients having no neck
      dissection and those having a selective dissection, with particular reference to
      shoulder dysfunction. DESIGN: Prospective study. SETTING: Regional Maxillofacial
      Unit, University Hospital Aintree, Liverpool, England. PATIENTS: Two hundred
      seventy-eight consecutive patients undergoing primary surgery for previously
      untreated oral and oropharyngeal squamous cell carcinoma between January 1, 1995,
      and December 31, 1999. MAIN OUTCOME MEASURE: The University of Washington Quality
      of Life questionnaire, administered on the day before surgery and at 6 months, at
      12 months, and more than 18 months after surgery. RESULTS: No neck dissection was
      performed in 58 patients (21%), a unilateral dissection in 181 (65%), and a
      bilateral dissection in 39 (14%). Patients with no neck dissection and those with
      unilateral level III or IV dissections had similar mean scores for shoulder
      dysfunction, whereas patients with unilateral level V and bilateral level III and
      IV dissections recorded much worse scores on average. CONCLUSIONS: There is
      little subjective morbidity associated with shoulder dysfunction after a
      unilateral level III or IV neck dissection compared with patients undergoing
      primary surgery without a neck dissection. More extensive surgery in the neck,
      whether bilaterally removing levels I to III or IV or extending posteriorly to
      include level V, is associated with statistically significantly worse shoulder
      dysfunction.

PMID- 14967743
TI  - Soft tissue deposits in neck dissections of patients with head and neck squamous
      cell carcinoma: prospective analysis of prevalence, survival, and its
      implications.
AB  - BACKGROUND: Soft tissue deposits of squamous cell carcinoma in the necks of
      patients with squamous cell carcinoma of the upper aerodigestive tract may
      represent either total effacement of a lymph node by carcinoma or extralymphatic
      deposits of carcinoma. There are few reports of their clinical or prognostic
      significance. METHODS: Data from 215 neck dissections from 155 patients with
      squamous cell carcinoma of the upper aerodigestive tract were studied
      prospectively to assess the prevalence of soft tissue deposits within the neck.
      The case notes of these patients were subsequently reviewed to analyze the effect
      on both the overall survival and recurrence-free survival. RESULTS: The
      prevalence rate for soft tissue deposits occurring alone was 10.3%; the
      prevalence rate for soft tissue deposits occurring with extracapsular spread was
      13.5%. The overall prevalence rate for soft tissue deposits was 23.9%. There was
      a statistically significant reduction in actuarial and recurrence-free survival
      in patients with soft tissue deposits compared with patients with pathologically
      node-negative necks (P=.001), and in patients with soft tissue deposits compared
      with those with pathologically node-positive necks without extracapsular spread
      (P=.001). No statistically significant differences were found between patients
      with soft tissue deposits and patients with pathologically node-positive necks
      with extracapsular spread, for actuarial survival or recurrence-free survival.
      CONCLUSIONS: In this series, soft tissue deposits were associated with an
      aggressive clinical course and poor survival. It is therefore important that
      histopathologists agree on a uniform terminology when reporting soft tissue
      deposits and actively look for their presence when examining neck dissection
      specimens.

PMID- 14967744
TI  - Postoperative adjuvant chemoradiotherapy in older patients with head and neck
      cancer.
AB  - BACKGROUND: In head and neck cancer, the locoregional failure of patients with
      positive margins, vascular or perineural invasion, and extracapsular spread is
      high and results in poor survival. OBJECTIVE: To assess the effect of adjuvant
      chemoradiotherapy in improving treatment outcomes among older patients with head
      and neck cancer. METHODS: Forty patients undergoing radical surgery (median age,
      73.5 years [range, 70-78 years]) were enrolled (35 men and 5 women; Eastern
      Cooperative Oncology Group performance status, grade 0-2). Disease sites included
      the oral cavity (10 patients), oropharynx (12 patients), hypopharynx (8
      patients), and larynx (10 patients); pathological TNM classifications included T1
      N2 (8 patients), T2 N1-2 (12 patients), T3 N0-2 (8 patients), and T4 N0-2 (12
      patients), with the following poor prognostic factors: positive margins (6
      patients), vascular invasion (14 patients), neural invasion (16 patients), and
      extracapsular spread (26 patients). All patients were treated with carboplatin
      (30 mg/m2 on days 1-5 of weeks 1, 3, and 5) concomitant with radiotherapy (54.0
      Gy to all risk volumes plus 10.0 Gy to high-risk volumes; 5 daily fractions of
      1.8 Gy each per week). RESULTS: No grade 4 toxicity was observed. Grade 3
      toxicity included mucositis (10 patients), neutropenia (6 patients), dermatitis
      (2 patients), and thrombocytopenia (1 patient). The radiotherapy dose
      administered was 52.0 Gy to all risk volumes plus 10.0 Gy to high-risk volumes.
      Thirty-two patients (80%) received 3 cycles, 6 (15%) received 2 cycles, and 2
      (5%) received 1 cycle. Three-year survival was as follows: disease-free survival,
      58%; overall survival, 64%; and local control, 79%. CONCLUSIONS: Adjuvant
      chemoradiotherapy may be successful in fit older patients. The results of
      adjuvant chemoradiotherapy were better than those observed in a comparable group
      treated with radiotherapy alone and were similar to those observed in a younger
      group with the same poor prognostic factors treated with adjuvant carboplatin
      plus radiotherapy.

PMID- 14967745
TI  - Impact of retropharyngeal lymph node metastasis in head and neck squamous cell
      carcinoma.
AB  - BACKGROUND: The impact of metastasis to the retropharyngeal lymph node (RPLN)
      group is poorly understood because of the difficult access of the retropharyngeal
      space. Previous studies concluding to the negative impact of RPLN metastasis rely
      heavily on radiographic assessment, which introduces the possibility of
      diagnostic error. OBJECTIVE: To better define the prognostic significance of
      metastatic retropharyngeal adenopathy in patients with non-nasopharyngeal
      squamous cell carcinoma of the head and neck. STUDY DESIGN: A retrospective
      cohort study of patients with non-nasopharyngeal squamous cell carcinoma of the
      head and neck who underwent resection of the RPLN group and were followed up for
      an average of 24 months. SETTING: Tertiary care academic medical center.
      PATIENTS: The 51 patients included in the study had been treated for advanced
      stage squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and/or
      supraglottic larynx via a surgical approach to the primary tumor that afforded
      access to the RPLN group. All patients underwent dissection and pathologic
      interpretation of the RPLNs, most patients received postoperative radiotherapy,
      and 43 patients met survival analysis criteria. MAIN OUTCOME MEASURES: Local and
      regional recurrence rates, the development of distant metastasis, and disease
      free and overall survival. RESULTS: Metastasis to the RPLN group was confirmed
      pathologically in 14 (27.5%) patients. There was no statistically significant
      difference between patients with and without RPLN metastasis in rates of local
      recurrence (24.8% vs 28.4%), regional recurrence (17.5% vs 19.6%), distant
      metastasis (17.0% vs 11.2%), disease-free survival (40.5% vs 30.5%), and overall
      survival (40.6% vs 38.5%). CONCLUSION: Metastasis to the RPLN group does not
      impact disease control or survival in patients with advanced non-nasopharyngeal
      squamous cell carcinoma of the head and neck treated with multimodality therapy.

PMID- 14967746
TI  - Prognostic factors in head and neck mucoepidermoid carcinoma.
AB  - OBJECTIVE: To analyze clinical, histological, and immunohistochemical prognostic
      factors in a large series of patients with mucoepidermoid carcinoma (MEC) treated
      in a single institution, using univariate and multivariate survival analyses.
      DESIGN: Inception cohort. SETTING: Referral center. PATIENTS: All patients
      diagnosed with head and neck MEC from a single cancer referral center from
      January 19, 1957, to July 12, 1997. MAIN OUTCOME MEASURES: Rates of local
      recurrence, regional and distant metastasis, and overall actuarial survival.
      RESULTS: Men represented 53.8% of the cohort, and the parotid gland and palate
      were affected by MEC in 35.2% and 23.7%, respectively. TNM stage I or II lesions
      comprised 50.3% of the tumors, and low-grade tumors comprised 45.2%, and the 5
      year overall survival was 70.2%. Univariate survival analysis revealed that age
      older than 40 years (P<.001), male sex (P=.005), fixed tumors (P=.002), invasion
      of adjacent structures (P=.004), T stage (P<.001), N stage (P<.001), clinical
      stage (P<.001), histological grade (P<.001), and expression of proliferating cell
      nuclear antigen (P<.001), Ki-67 (P<.001), and p53 (P<.001) correlated with a poor
      prognosis. Expression of carcinoembryonic antigen (P=.01) and bcl-2 (P<.001)
      correlated with a better prognosis. CONCLUSION: Age older than 40 years, fixed
      tumors, T and N stage, and histological grade are independent significant
      prognostic factors in patients with MEC.

PMID- 14967747
TI  - Pectoralis major myocutaneous flap vs revascularized free tissue transfer:
      complications, gastrostomy tube dependence, and hospitalization.
AB  - OBJECTIVE: To evaluate the factors related to surgical complications, rate of
      gastrostomy tube (G-tube) dependence, and hospitalization in patients undergoing
      reconstruction with a pectoralis myocutaneous flap vs a soft-tissue
      revascularized flap. DESIGN: Quasi-experimental case series with a historic
      control group. POPULATION: A total of 179 patients (138 men and 41 women) with a
      mean (SD) age of 58 (14) years treated between January 1, 1986, and December 31,
      1995, with a pectoralis flap (108 patients) or a revascularized free flap (71
      patients). METHODS: Inclusion criteria were first or second extirpation,
      reconstruction with soft-tissue flap, or defect including the upper aerodigestive
      tract. Exclusion criteria were secondary reconstruction, or reconstruction for
      salvage of a complication. RESULTS: Although the major complication rate was not
      significantly different according to reconstructive approach, hypopharyngeal
      defects had a significantly higher major complication rate of 30% (6/20) compared
      with 8% (13/159) for other defect sites (P<.003). The minor complication rate was
      higher in the pectoralis group, at 57% (62/108), than in the revascularized flap
      group, at 21% (15/71) (P<.001). G-tube dependence was higher in the pectoralis
      group at 42% (40/96), in contrast to the revascularized flap group at 16% (10/63)
      (P<.001). G-tube dependence was 25% higher in patients who underwent salvage
      surgery after radiation (42% [30/72]) than in patients treated with postoperative
      radiation (17% [12/69]) (P<.004). Revascularized flaps helped ameliorate the
      effects of radiation before surgery; 56% (23/41) of the patients who received
      pectoralis flaps were G-tube dependent, while the rate of G-tube dependence in
      the revascularized flap group was 23% (7/31) (P<.004). Hospitalization was longer
      in the pectoralis group (14 days) than the revascularized flap group (12 days)
      (P<.006). CONCLUSION: Patients who undergo reconstruction with a pectoralis flap
      have significantly higher minor complication rates, a higher rate of G-tube
      dependence, and longer hospitalization than patients who undergo reconstruction
      with a soft-tissue revascularized flap.

PMID- 14967748
TI  - The use of diathermy scissors in parotid gland surgery.
AB  - OBJECTIVE: To evaluate the benefits, as well as the possible complications, of
      the use of diathermy scissors in parotid gland surgery. DESIGN: Prospective study
      of the surgical procedures of the diathermy scissors and a retrospective
      comparison with a conventionally treated control group concerning cut-closure
      time. SETTING: Tertiary care referral academic center. PATIENTS: Prospective
      examination of 30 unselected patients undergoing superficial (n=23) or
      subtotal/total (n=10) parotidectomies performed with diathermy scissors.
      Indications were benign tumors (n=18), malignant tumors (n=12), and cystic
      lesions (n=3). In a control group (n=50), 36 superficial and 21 subtotal/total
      parotidectomies were performed. RESULTS: The use of diathermy scissors reduces
      the need to frequently change dissecting and coagulating surgical instruments.
      The scissors reduce intraoperative bleeding and therefore improve visualization
      and orientation in the surgical field. Postoperative bleeding or seroma and Frey
      syndrome were not observed. In 1 case, a salivary fistula was present for 3
      weeks. Three cases of transient facial weakness occurred, all of which completely
      resolved by 6 months after surgery. In the control group, the cut-closure time
      ranged from 50 to 120 minutes (average, 87.6 minutes) during superficial
      parotidectomy; it ranged from 80 to 160 minutes (average, 130.0 minutes) during
      subtotal and total parotidectomy. In comparison, in the study group, the average
      time gain was 16 minutes during superficial parotidectomy when diathermy scissors
      were used, a statistically significant difference (P=.03). During subtotal and
      total parotidectomy with diathermy scissors, the average time gain was 19.3
      minutes and was statistically not significant (P=.23). CONCLUSIONS: The results
      of the present study show that diathermy scissors are very well suited for most
      of the surgical steps in parotid gland surgery. They provide an elegant, safe,
      and fast surgical procedure, especially in the hands of an experienced surgeon.

PMID- 14967749
TI  - Quality of life after adenotonsillectomy for obstructive sleep apnea in children.
AB  - OBJECTIVE: To study changes in quality of life in children after
      adenotonsillectomy for obstructive sleep apnea (OSA) documented by full-night
      polysomnography. DESIGN AND SETTING: Prospective study of children with OSA at
      the University of New Mexico Children's Hospital, Albuquerque. METHODS:
      Caregivers for children were asked to complete the OSA-18 quality of life survey
      prior to polysomnography. Children who met inclusion criteria and had a
      respiratory distress index higher than 1 were enrolled in the study and underwent
      adenotonsillectomy. Caregivers completed a second OSA-18 survey within 6 months
      of surgery. Scores from the preoperative and postoperative surveys were compared
      using the paired t test. RESULTS: The study population included 60 children (mean
      age, 7.1 [range, 3-12] years), of whom 43 (72%) were male and 30 (50%) were
      younger than 6 years. Forty-seven children (78%) had a respiratory distress index
      of 10 or higher. The mean interval between the 2 surveys was 126 days. The mean
      total OSA-18 score was 71.4 before surgery and 35.8 after surgery. The domain
      with the greatest change in mean score was sleep disturbance, which improved by
      11.5. The changes in total score, in the scores for each domain, and for each
      item of the OSA-18 survey were highly significant (P<.002). CONCLUSIONS: Children
      without significant comorbidities show a marked improvement in the domains of
      sleep disturbance, physical symptoms, emotional symptoms, and daytime functioning
      as reported by their caregivers after adenotonsillectomy for OSA.

PMID- 14967750
TI  - Changes in quality of life and respiratory disturbance after extended
      uvulopalatal flap surgery in patients with obstructive sleep apnea.
AB  - OBJECTIVE: To evaluate the subjective and objective outcomes of extended
      uvulopalatal flap (EUPF) surgery in patients with obstructive sleep apnea.
      DESIGN: Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), Snore
      Outcomes Survey (SOS), Epworth Sleepiness Scale (ESS), and polysomnography were
      performed preoperatively and then 6 months postoperatively. SETTING: Tertiary
      care, sleep disorders referral center. PATIENTS: Fifty-five consecutive patients
      (52 men and 3 women; mean age, 45 years) with obstructive sleep apnea.
      INTERVENTION: EUPF surgery. MAIN OUTCOME MEASURES: Overnight polysomnography
      variables included respiratory distress index (RDI), snore index, minimum oxygen
      saturation, sleep stages 1 and 2, sleep stages 3 and 4, rapid eye movement, and
      sleep efficiency. Questionnaire variables included SF-36, SOS, and ESS scores.
      Success of the operation was defined as a more than 50% reduction of the RDI from
      the initial value and a postoperative RDI of less than 20. RESULTS: The overall
      success rate of the EUPF surgery was 82%; the RDI, snore index, and minimum
      oxygen saturation improved significantly after surgery (P<.001). Sleep
      architecture in overnight polysomnography remained unchanged (P=.48 and P=.74).
      Patients demonstrated significant improvement in both their SOS and ESS scores
      (P<.001) and significant increases in 7 of 8 SF-36 subscales (P<.05 for all).
      However, there was poor correlation between the improvement in quality of life
      and the reduction in sleep-related respiratory events. CONCLUSIONS: Extended
      uvulopalatal flap surgery can greatly reduce sleep-related adverse events and
      proves to be an effective therapy to enhance the quality of life of patients with
      obstructive sleep apnea. This study also suggests that subjective and objective
      outcomes are equally important when reporting the results of EUPF surgery.

PMID- 14967751
TI  - Age-, site-, and time-specific differences in pediatric deep neck abscesses.
AB  - OBJECTIVE: To clarify presentations, organisms, and locations of deep neck
      abscesses in children. DESIGN: Retrospective review. SETTING: Tertiary children's
      hospital. The study population comprised 169 patients younger than 19 years who
      were surgically treated for deep neck abscesses between 1989 and 1999. MAIN
      OUTCOME MEASURE: Resolution of abscess. RESULTS: Neck mass (91%), fever (86%),
      cervical adenopathy (83%), poor oral intake (66%), and neck stiffness (59%) were
      common in all ages. Patients younger than 4 years, compared with patients 4 years
      or older, presented with agitation (50% vs 14%), cough (35% vs 14%), drooling
      (27% vs 12%), lethargy (46% vs 33%), oropharyngeal abnormalities (45% vs 60%),
      respiratory distress (5% vs 2%), retractions (5% vs 2%), rhinorrhea (53% vs 15%),
      stridor (4% vs 2%), and trismus (14% vs 53%). Children younger than 1 year were
      infected with Staphylococcus aureus (79%) vs group A streptococcus (6%). Children
      1 year or older were infected with group A streptococcus (29%) vs S aureus (16%).
      Retropharyngeal or parapharyngeal regions were involved in children 1 year or
      older (49%) vs younger than 1 year (21%). Anterior or posterior triangles and
      submandibular or submental regions were involved in 39% and 36%, respectively, of
      children younger than 1 year vs 30% and 23%, respectively, of children 1 year or
      older. Retropharyngeal and parapharyngeal abscesses yielded group A streptococcus
      (34%) vs S aureus (11%). Anterior and posterior triangle abscesses yielded S
      aureus (35%) vs group A streptococcus (19%), as did submandibular and submental
      abscesses (42% vs 19%). CONCLUSIONS: Abscesses in children younger than 1 year
      affected anterior or posterior triangles and submandibular or submental regions,
      yielding S aureus. Abscesses in children 1 year or older affected retropharyngeal
      or parapharyngeal regions, yielding group A streptococcus.

PMID- 14967752
TI  - The effects of breath-holding on vocal fold adduction: implications for safe
      swallowing.
AB  - OBJECTIVE: To determine the effects, if any, of 3 different breath-holding
      techniques on a person's ability to attain vocal fold closure (VFC) to
      successfully complete swallowing maneuvers. DESIGN: Prospective, randomized
      study. SETTING: Private practice. PATIENTS: A total of 150 healthy volunteers
      recruited from private practice patients and community volunteers. Intervention
      Group 1 received the easy breath-hold instruction; group 2 received the
      inhale/easy breath-hold instruction; and group 3 received the hard breath-hold
      instruction. MAIN OUTCOME MEASURE: Closure of true and false vocal folds
      following the breath-hold instruction. RESULTS: In the easy breath-hold group,
      true VFC occurred in 82% of the subjects, and closure of both the true and false
      vocal folds occurred in 30%. In the inhale/easy breath-hold group, true VFC
      occurred in 62%, and closure of both folds occurred in 46%. In the hard breath
      hold group, true VFC occurred in 86%, and closure of both folds occurred in 64%.
      The differences among the 3 groups were significant for true VFC (chi2=9.242;
      P=.01) and for closure of both folds (chi2=11.625; P=.003). CONCLUSIONS: The hard
      breath-hold instruction was the most effective method to attain full laryngeal
      closure, and the inhale/easy breath-hold instruction was the least effective
      method to attain true VFC for safe swallowing.

PMID- 14967753
TI  - Expression of annexin A1 in normal and chronically inflamed nasal mucosa.
AB  - OBJECTIVE: To examine the expression pattern of annexin A1 in normal and
      chronically inflamed nasal mucosa to investigate its possible role in nasal
      inflammation. DESIGN: Immunohistochemical analysis. SUBJECTS: Samples of middle
      turbinates from 5 healthy subjects and 5 patients with perennial rhinitis, and
      samples of nasal polyps from 7 patients. INTERVENTIONS: Annexin A1 expression was
      examined with a standard immunohistochemical protocol on paraffin-embedded
      sections. RESULTS: Annexin A1 was highly expressed by ciliated cells, where it
      was concentrated on the apical surface and within the cilia. Goblet cells and
      nondifferentiated basal epithelial cells did not stain. In the glands of the
      lamina propria, intense staining was found in the cytoplasm and in the nuclei of
      the cells in the duct epithelium, whereas acinar cells did not stain. Intense
      cytoplasmic staining was observed in infiltrating polymorphonuclear cells and
      macrophages. No differences in the pattern or the level of expression of annexin
      A1 were found in the epithelial cells and glands of normal and chronically
      inflamed (perennial rhinitis or polyps) nasal mucosa. CONCLUSION: These results
      suggest that the expression of annexin A1 in respiratory epithelium of nasal
      mucosa is related to cell type and differentiation status of the cells and is not
      significantly altered by inflammatory diseases.

PMID- 14967754
TI  - What is the real incidence of vestibular schwannoma?
AB  - OBJECTIVES: To present the incidence of vestibular schwannoma (VS) in Denmark,
      compare the incidence with that of previous periods, and discuss the real
      incidence of VS. DESIGN, SETTING, AND PATIENTS: Prospective registration of all
      diagnosed VS in Denmark, with a population of 5.1 to 5.2 million, during the 6
      years from January 1996 through December 2001. Incidence in this period was
      compared with that of 3 previous periods (July 1976 through June 1983 [first
      period], July 1983 through June 1990 [second period], and July 1990 through
      December 1995 [third period]). RESULTS: In the 1996-2001 period, 542 cases of VS
      were diagnosed, representing a mean incidence of 17.4 VS/1 million inhabitants
      per year. Of these, 227 tumors underwent operation, 14 underwent irradiation, and
      301 were allocated to observation (wait-and-scan policy). One hundred sixty-six
      tumors were intrameatal. Size of extrameatal tumors was small in 104; medium in
      194; large in 68; and giant (>40 mm) in 10. Compared with incidences of 7.8 VS/1
      million inhabitants per year in the first, 9.4 VS/1 million inhabitants in the
      second, and 12.4 VS/1 million inhabitants in the third periods, the incidence for
      the 1996-2001 period represents an increase to 17.4 VS/1 million inhabitants per
      year. The mean incidence for the entire 25.5-year period was 11.5 VS/1 million
      inhabitants per year. CONCLUSIONS: An estimate of a realistic mean incidence of
      VS depends on the observation period. Our 25.5-year registration of an entire
      population showed a mean incidence of 11.5 VS/1 million inhabitants per year.
      However, the latest period registered represents an incidence of 17.4 VS/1
      million inhabitants per year, which, combined with a probable further increase of
      diagnosed tumors in forthcoming years, suggests a realistic incidence of
      approximately 13 VS/1 million inhabitants per year.

PMID- 14967755
TI  - Hearing threshold in sport divers: is diving really a hazard for inner ear
      function?
AB  - OBJECTIVE: To investigate the effect of scuba diving on the hearing threshold of
      sport divers who have no history of excessive noise exposure or of diving-related
      inner ear damage. DESIGN: Cross-sectional controlled comparison study. SETTING:
      General sports diving community. PARTICIPANTS: Sixty sport divers with an average
      of 650 dives each and at least 4 years of diving experience (mean, 10 years) were
      compared with a control group of 63 nondivers from our hospital staff or patients
      referred for rhinologic problems or benign tumors of the salivary gland. MAIN
      OUTCOME MEASURE: After microscopic otoscopy and tympanometry, we used pure-tone
      audiometry to measure the hearing threshold for air and bone conduction. The
      participants were divided into 3 age groups, and the hearing test results for
      both ears combined were statistically compared. RESULTS: There were no
      statistically significant differences in the hearing thresholds between sport
      divers and nondivers. CONCLUSIONS: The reduced hearing levels of professional
      divers found in other studies are probably due to the high noise levels that they
      have to deal with or may be a result of inner ear accidents.

PMID- 14967756
TI  - Prevalence of thyroid dysfunction in patients with Meniere's disease.
AB  - OBJECTIVE: To estimate the prevalence of hypothyroidism in a population of
      patients with Meniere's disease (MD). DESIGN: Retrospective case-control study
      comparing the use of thyroid hormone supplements between patients with MD and
      controls. SETTING: Outpatient neurology clinic specializing in the management of
      patients experiencing dizziness. PATIENTS: Fifty patients who met the 1995
      American Academy of Otolaryngology criteria for MD and 50 controls matched for
      age and sex also experiencing dizziness. RESULTS: The 50 patients who met the
      criteria for MD were identified from a database of more than 2000 patients with
      dizziness seen over a 5-year period. Of these, 16 (32%) were taking thyroid
      hormone supplements in contrast to 2 (4%) of the 50 matched controls (P<.001).
      The median age of the patients with MD was 60 years, and 5 (19%) of the 26
      patients younger than 60 years were taking thyroid hormone supplements, compared
      with 11 (46%) of 24 patients 60 years or older (P<.05). There were no
      statistically significant differences in the severity of hearing loss, pattern of
      hearing loss, or prevalence of bilateral hearing loss between patients with MD
      who were taking thyroid hormone supplements and patients with MD who were not.
      CONCLUSION: Meniere's disease is associated with corrected hypothyroidism.

PMID- 14967757
TI  - Acute vestibular neuritis visualized by 3-T magnetic resonance imaging with high
      dose gadolinium.
AB  - Sudden idiopathic unilateral loss of vestibular function without other signs or
      symptoms is called acute vestibular neuritis. It has been suggested that
      reactivation of human herpes simplex virus 1 could cause vestibular neuritis,
      Bell palsy, and sudden unilateral hearing loss. Enhancement of the facial nerve
      on gadolinium-enhanced magnetic resonance imaging (MRI) is a common finding in
      Bell palsy, but enhancement of the vestibular nerve has never been reported in
      acute vestibular neuritis. We present 2 consecutive cases of acute vestibular
      neuritis where high-field-strength MRI (3.0 T) with high-dose (0.3 mmol/kg of
      body weight) gadolinium-pentetic acid showed isolated enhancement of the
      vestibular nerve on the affected side only. These findings support the hypothesis
      of a viral and inflammatory cause of acute vestibular neuritis and might have
      implications for its treatment.

PMID- 14967758
TI  - Airway management in mucopolysaccharide storage disorders.
AB  - Mucopolysaccharidoses (MPS), a group of disorders caused by a genetic disruption,
      create a special challenge for the otolaryngologist. With the rare types of MPS
      IV and MPS 1 S, a skilled practitioner is required to abate airway management
      complications. The erratic deposits of mucopolysaccharides throughout the trachea
      should be taken into account when decisions to stent the airway are made. Proper
      management requires to provide an airway that is custom-made to meet the
      patient's needs. This is a case-by-case presentation of 3 patients with MPS who
      presented to the Children's Hospital of Michigan with progressive respiratory
      embarrassment. Discussed are the various issues revolving around our ability to
      provide proper airway management, from intubation to tracheostomy tube placement.

PMID- 14967759
TI  - Pathology quiz case 1. Atypical fibroxanthoma of the auricle.

PMID- 14967760
TI  - Pathology quiz case 2. Primary intestinal-type sinonasal adenocarcinoma.

PMID- 14967761
TI  - Radiology quiz case 1. Meningioma of the internal auditory canal.

PMID- 14967762
TI  - Radiology quiz case 2. Retained foreign bodies mimicking a first branchial cleft
      cyst.

PMID- 14967763
TI  - Fatigue in multiple sclerosis: is the picture getting simpler or more complex?

PMID- 14967764
TI  - Spinocerebellar ataxia type 17: latest member of polyglutamine disease group
      highlights unanswered questions.

PMID- 14967765
TI  - The congenital and limb-girdle muscular dystrophies: sharpening the focus,
      blurring the boundaries.
AB  - During the past decade, outstanding progress in the areas of congenital and limb
      girdle muscular dystrophies has led to staggering clinical and genetic
      complexity. With the identification of an increasing number of genetic defects,
      individual entities have come into sharper focus and new pathogenic mechanisms
      for muscular dystrophies, like defects of posttranslational O-linked
      glycosylation, have been discovered. At the same time, this progress blurs the
      traditional boundaries between the categories of congenital and limb-girdle
      muscular dystrophies, as well as between limb-girdle muscular dystrophies and
      other clinical entities, as mutations in genes such as fukutin-related protein,
      dysferlin, caveolin-3 and lamin A/C can cause a striking variety of phenotypes.
      We reviewed the different groups of proteins currently recognized as being
      involved in congenital and limb-girdle muscular dystrophies, associated them with
      the clinical phenotypes, and determined some clinical and molecular clues that
      are helpful in the diagnostic approach to these patients.

PMID- 14967766
TI  - The relationship between diffuse axonal damage and fatigue in multiple sclerosis.
AB  - BACKGROUND: Fatigue is a common and distressing symptom for patients with
      multiple sclerosis (MS). There is growing evidence that fatigue in MS has a
      central nervous system component. We hypothesized that diffuse cerebral axonal
      damage could be associated with fatigue and used proton magnetic resonance
      spectroscopy to noninvasively measure axonal damage or loss in the brains of
      patients with MS. OBJECTIVE: To assess the strength of the relationship between
      central brain N-acetylaspartate and fatigue. DESIGN: Data from 73 patients who
      had undergone proton magnetic resonance spectroscopy imaging and completed the
      Fatigue Severity Scale questionnaire were analyzed. RESULTS: The N
      acetylaspartate-creatine ratio (NAA/Cr) was significantly lower in the high
      fatigue group than the low-fatigue group (mean +/- SD, 2.69 +/- 0.29 and 2.99 +/-
      0.33, respectively. P =.003). Independent of the Kurtzke Expanded Disability
      Status Scale, T2 lesion volume, age, and disease duration, NAA/Cr was
      significantly lower in the high-fatigue group as compared with the low-fatigue
      group. There was a statistically significant linear correlation between the
      Fatigue Severity Scale scores and NAA/Cr (Spearman rank rho = -0.361, P =.02).
      CONCLUSIONS: The results of this study, combined with those of others, suggest
      that widespread axonal dysfunction is associated with fatigue in MS. Increased
      recruitment of cortical areas and pathways in response to brain injury may be
      responsible for the patient's sense that the effort required to perform actions
      is disproportionately high.

PMID- 14967767
TI  - Possible reduced penetrance of expansion of 44 to 47 CAG/CAA repeats in the TATA
      binding protein gene in spinocerebellar ataxia type 17.
AB  - BACKGROUND: Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant
      cerebellar ataxia caused by expansion of CAG/CAA trinucleotide repeats in the
      TATA-binding protein (TBP) gene. Because the number of triplets in patients with
      SCA17 in previous studies ranged from 43 to 63, the normal number of
      trinucleotide units has been considered to be 42 or less. However, some healthy
      subjects in SCA17 pedigrees carry alleles with the same number of expanded
      repeats as patients with SCA17. OBJECTIVE: To investigate the minimum number of
      CAG/CAA repeats in the TBP gene that causes SCA17. DESIGN: We amplified the
      region of the TBP gene containing the CAG/CAA repeat by means of polymerase chain
      reaction and performed fragment and sequence analyses. PATIENTS: The subjects
      included 734 patients with SCA (480 patients with sporadic SCA and 254 patients
      with familial SCA) without CAG repeat expansions at the SCA1, SCA2, Machado
      Joseph disease, SCA6, SCA7, or dentatorubral-pallidolluysian atrophy loci, with
      162 healthy subjects, 216 patients with Parkinson disease, and 195 with Alzheimer
      disease as control subjects. RESULTS: Eight patients with SCA possessed an allele
      with more than 43 CAG/CAA repeats. Among the non-SCA groups, alleles with 43 to
      45 repeats were seen in 3 healthy subjects and 2 with Parkinson disease. In 1 SCA
      pedigree, a patient with possible SCA17 and her healthy sister had alleles with
      45 repeats. A 34-year-old man carrying alleles with 47 and 44 repeats (47/44) had
      developed progressive cerebellar ataxia and myoclonus at 25 years of age, and he
      exhibited dementia and pyramidal signs. He was the only affected person in his
      pedigree, although his father and mother carried alleles with mildly expanded
      repeats (44/36 and 47/36, respectively). In another pedigree, 1 patient carried a
      43-repeat allele, whereas another patient had 2 normal alleles, indicating that
      the 43-repeat allele may not be pathologic in this family. CONCLUSIONS: We
      estimate that 44 CAG/CAA repeats is the minimum number required to cause SCA17.
      However, the existence of unaffected subjects with mildly expanded triplets
      suggests that the TBP gene mutation may not penetrate fully. Homozygosity of
      alleles with mildly expanded triplet repeats in the TBP gene might contribute to
      the pathologic phenotype.

PMID- 14967768
TI  - When sporadic disease is not sporadic: the potential for genetic etiology.
AB  - BACKGROUND: Approximately 2% of Alzheimer disease cases and 10% to 15% of prion
      disease cases are due to mutations in autosomal dominant genes. Mutations have
      been found in patients without family histories of neurological disease.
      OBJECTIVES: To emphasize the need for consideration of a genetic etiology of
      prion disease and early-onset Alzheimer disease, regardless of the absence of a
      significant family history, as well as the need for pretest genetic counseling of
      all patients or their families. DESIGN: Three case reports. PATIENTS AND RESULTS:
      Patient 1, a 53-year-old man with possible Creutzfeldt-Jakob disease, was
      enrolled in a research study that included sequencing of the prion protein gene.
      Although there was no family history of neurological disease, an E200K mutation
      was found. This unexpected result caused the family significant distress. Patient
      2, a 55-year-old woman with biopsy-proven Creutzfeldt-Jakob disease, participated
      in a prion disease research study. Her family was counseled about the possibility
      of hereditary Creutzfeldt-Jakob disease, despite the lack of family history.
      After assessing the ramifications, the family decided not to learn about the
      patient's genetic test results. Patient 3 was a 54-year-old man with a 6-year
      history of memory loss. A diagnosis of probable Alzheimer disease was given, and
      the patient and his family were counseled on the availability of presenilin 1
      testing, although there was no known family history of dementia. The family
      agreed to testing, and a presenilin 1 mutation was identified. CONCLUSIONS:
      Certain neurodegenerative diseases may have a genetic etiology, despite the lack
      of a positive family history. Revealing a newly discovered hereditary cause of
      Creutzfeldt-Jakob disease or Alzheimer disease can have a profound effect on
      families. Pretest counseling on genetic issues is essential to better prepare
      families and to allow them to make an informed choice about learning genetic test
      results.

PMID- 14967769
TI  - Infratentorial lesions predict long-term disability in patients with initial
      findings suggestive of multiple sclerosis.
AB  - BACKGROUND: The number and volume of abnormalities on baseline brain magnetic
      resonance images in patients with initial findings suggestive of multiple
      sclerosis are known to predict outcome in terms of disability. However, no long
      term data exist on specific locations or types of lesions. OBJECTIVE: To assess
      the long-term predictive value of baseline magnetic resonance imaging parameters,
      including location of lesions and gadolinium-enhancing and hypointense lesions in
      patients with initial findings suggestive of multiple sclerosis for the
      occurrence of clinically relevant disability as defined by an Expanded Disability
      Status Scale score of 3. PATIENTS: After a median follow-up period of 8.7 years,
      the medical records of 42 patients were reviewed and assessed for time until
      patients received an Expanded Disability Status Scale score of 3. Magnetic
      resonance imaging parameters were dichotomized according to maximum accuracy and
      then used to calculate hazard ratios using the Cox model for proportional hazard
      ratios. RESULTS: Conversion to clinically definite multiple sclerosis was
      observed in 26 patients (62%), of whom 14 (54%) progressed to an Expanded
      Disability Status Scale score of 3. Two or more infratentorial lesions best
      predicted long-term disability (hazard ratio, 6.3). Gadolinium-enhancing and
      hypointense T1-weighted lesions did not show prognostic value. CONCLUSION:
      Infratentorial lesions are related to long-term prognosis for patients with
      initial findings suggestive of multiple sclerosis and thus may help to identify
      patients at high risk for earlier occurrence of clinically relevant disability.

PMID- 14967770
TI  - Specificity of Barkhof criteria in predicting conversion to multiple sclerosis
      when applied to clinically isolated brainstem syndromes.
AB  - BACKGROUND: Barkhof criteria have been adopted to demonstrate dissemination in
      space in the new multiple sclerosis diagnostic criteria because of their high
      specificity for predicting conversion to multiple sclerosis. One of the 4 Barkhof
      criteria is the presence of an infratentorial lesion. In clinically isolated
      syndromes (CIS) of the brainstem (CISB), the infratentorial criterion does not
      demonstrate dissemination in space, raising the possibility that the criteria may
      be less specific in CISB, as compared with specificity in other CIS, in which all
      4 criteria demonstrate dissemination in space. OBJECTIVE: To compare the validity
      indices of Barkhof criteria in CISB with those in other CIS. DESIGN: Inception
      cohort with median follow-up of 34 months for CISB and 40 months for other CIS.
      SETTING: Institutional ambulatory referral center. PATIENTS: A sample of 51
      patients with CISB and 102 patients with other CIS (46 with myelitis and 56 with
      optic neuritis) was analyzed. Barkhof criteria, with a cutoff of 3 of 4, were
      applied to magnetic resonance imaging performed at baseline. Four combinations
      each containing 3 parameters were also applied, with a cutoff of 2 of 3. MAIN
      OUTCOME MEASURE: Specificity of unmodified Barkhof criteria and of the 4
      combinations to predict conversion to clinically definite multiple sclerosis.
      RESULTS: The specificity of the criteria in CISB was 61% against 73% in other
      CIS. The combinations that retained the infratentorial lesion parameter had lower
      specificities in the CISB group; in analysis of the group with other CIS, no such
      differences were found. CONCLUSION: The infratentorial lesion criterion is
      responsible for the lower specificity of Barkhof criteria in CISB.

PMID- 14967771
TI  - Prediction of neuropsychological impairment in multiple sclerosis: comparison of
      conventional magnetic resonance imaging measures of atrophy and lesion burden.
AB  - BACKGROUND: Cognition and magnetic resonance imaging correlations are well
      established in patients with multiple sclerosis (MS), but it is unclear whether
      lesion burden or atrophy accounts for most of the predictive variance. These
      indices have been directly compared in only a few studies. No such study included
      measurement of the third ventricle, which was strongly predictive of
      neuropsychological competence in the early literature. Furthermore, few studies
      accounted for the influence of age, premorbid intelligence, or depression.
      OBJECTIVE: To determine if conventional measures of lesion burden or atrophy
      predict cognitive dysfunction in MS while accounting for age, premorbid
      intelligence, and depression. METHODS: We studied 37 patients with MS and 27
      controls matched according to demographic variables. Correlations between
      neuropsychological tests and the following magnetic resonance imaging indices
      were considered: T1 hypointense lesion volume, fluid-attenuated inversion
      recovery hyperintense lesion volume, third ventricle width, bicaudate ratio, and
      brain parenchymal fraction. Regression models predicting neuropsychological
      performance controlled for the effects of age, premorbid intelligence, and
      depression. We included only those tests discriminating patients with MS from
      controls. RESULTS: In each regression model, third ventricle width was the sole
      magnetic resonance imaging measure retained. When this variable was removed from
      consideration, brain parenchymal fraction was retained in all analyses.
      CONCLUSIONS: Brain atrophy accounts for more variance than lesion burden in
      predicting cognitive impairment in MS, and central atrophy in particular is
      strongly associated with neuropsychological morbidity. This finding may be
      explained in part by atrophy of the thalamus, a deep gray matter structure that
      mediates cognitive function via cortical and subcortical pathways. Enthusiasm for
      the clinical utility of third ventricle width is tempered by modest intraobserver
      and interobserver reliability.

PMID- 14967772
TI  - Auditory processing in severely brain injured patients: differences between the
      minimally conscious state and the persistent vegetative state.
AB  - BACKGROUND: The minimally conscious state (MCS) is a recently defined clinical
      condition; it differs from the persistent vegetative state (PVS) by the presence
      of inconsistent, but clearly discernible, behavioral evidence of consciousness.
      OBJECTIVE: To study auditory processing among patients who are in an MCS,
      patients who are in a PVS, and healthy control subjects. METHODS: By means of
      (15)O-radiolabeled water-positron emission tomography, we measured changes in
      regional cerebral blood flow induced by auditory click stimuli in 5 patients in
      an MCS, 15 patients in a PVS, and 18 healthy controls. RESULTS: In both patients
      in an MCS and the healthy controls, auditory stimulation activated bilateral
      superior temporal gyri (Brodmann areas 41, 42, and 22). In patients in a PVS, the
      activation was restricted to Brodmann areas 41 and 42 bilaterally. We also showed
      that, compared with patients in a PVS, patients in an MCS demonstrated a stronger
      functional connectivity between the secondary auditory cortex and temporal and
      prefrontal association cortices. CONCLUSIONS: Although assumptions about the
      level of consciousness in severely brain injured patients are difficult to make,
      our findings suggest that the cerebral activity observed in patients in an MCS is
      more likely to lead to higher-order integrative processes, thought to be
      necessary for the gain of conscious auditory perception.

PMID- 14967773
TI  - Minimal hepatic encephalopathy: longitudinal effects of liver transplantation.
AB  - BACKGROUND: The long-term effects of liver transplantation (LT) on minimal
      hepatic encephalopathy are poorly documented. OBJECTIVE: To assess the cognitive
      performance of patients with cirrhosis and without overt encephalopathy, before
      and after LT. DESIGN: Longitudinal study comparing cognitive performance of
      patients with cirrhosis before LT and 6 to 18 months after LT, with matched
      control patients. SETTING: University medical center. RESULTS: Six months after
      LT, patients had improved their performance in visuospatial and selective
      attention, visuospatial short-term and long-term memory, and language tasks.
      After 18 months, a further improvement was found for selective attention and
      verbal short-term memory, while no other cognitive functions varied over time.
      CONCLUSIONS: The present findings confirm preliminary studies showing that LT
      improves cognitive functions in patients with cirrhosis. The cognitive
      improvement is not generalized, but appears prominent in attention and memory
      and, once achieved, remains stable. Rates of recovery differ, being early for
      some functions and later for others.

PMID- 14967774
TI  - The cognitive benefits of galantamine are sustained for at least 36 months: a
      long-term extension trial.
AB  - BACKGROUND: Alzheimer disease (AD) causes progressive cognitive and functional
      decline over years. Although cholinesterase inhibitors have demonstrated efficacy
      in studies lasting 3 to 6 months, little is known about long-term therapy.
      OBJECTIVE: To report the long-term cognitive effects of galantamine hydrobromide
      given continuously for 36 months in AD patients. PARTICIPANTS: Subjects were 194
      US patients with mild to moderate AD who had been randomized to continuous
      galantamine therapy in either of 2 double-blind placebo-controlled trials.
      Subjects subsequently received open-label continuous galantamine therapy for up
      to 36 months. MAIN OUTCOME MEASURES: Effects on cognition were analyzed as change
      from study enrollment baseline in scores on the Alzheimer's Disease Assessment
      Scale-11-item cognitive subscale. Cognitive decline in galantamine-treated
      subjects was compared with that in a clinically similar historical control sample
      of AD patients who had received placebo for 12 months and with the mathematically
      predicted decline of untreated patients over 36 months. The rate of cognitive
      decline of patients who completed the entire 36-month trial (n = 119) was
      compared with that of patients who withdrew for any reason during the long-term
      open-label extension (n = 75). An inverted responder analysis was also performed
      in 36-month completers. RESULTS: Patients treated continuously with galantamine
      for 36 months increased a mean +/- SE of 10.2 +/- 0.9 points on the Alzheimer's
      Disease Assessment Scale-11-item cognitive subscale-a substantially smaller
      cognitive decline (approximately 50%) than that predicted for untreated patients.
      Patients discontinuing galantamine therapy before 36 months had declined at a
      similar rate before discontinuation as those completing 36 months of treatment.
      Almost 80% of patients who received galantamine continuously for up to 36 months
      seemed to demonstrate cognitive benefits compared with those predicted for
      untreated patients. CONCLUSIONS: Cognitive decline over 36 months of continuous
      galantamine treatment was substantially less than the predicted cognitive decline
      of untreated patients with mild to moderate dementia. Thus, the cognitive
      benefits of galantamine seemed to be sustained for at least 36 months. These
      findings suggest that galantamine slows the clinical progression of AD.

PMID- 14967775
TI  - Peripheral nerve involvement in spinocerebellar ataxias.
AB  - BACKGROUND: In autosomal dominant cerebellar ataxias (ADCAs), it is unclear
      whether the associated peripheral nerve involvement is always a typical length
      dependent axonopathy rather than primary neuronopathy due to neuronal
      degeneration in the spinal anterior horns and/or dorsal root ganglia. OBJECTIVE:
      To study the nature and extent of peripheral nerve involvement in patients with
      ADCA. PATIENTS AND METHODS: Standardized clinical and electrophysiologic studies
      of 27 genotyped patients with ADCA were conducted prospectively, with special
      emphasis on the distinction between primary neuronopathy and dying-back
      axonopathy. RESULTS: Electrophysiologic evidence of involvement of the peripheral
      nervous system was present in 70% of patients. Findings were compatible with
      dying-back axonopathy in 30%, while in 40% of patients, neuronopathy was
      diagnosed. Patients with spinocerebellar ataxia (SCA) 1 and SCA2 mostly displayed
      features of neuronopathy, while patients with SCA3 and SCA7 displayed both
      neuronopathy and axonopathy. In SCA6, no significant peripheral nerve involvement
      was demonstrated. We did not observe an influence of age, disease duration, or
      ataxia severity on the presence or type of peripheral nerve involvement.
      CONCLUSIONS: Peripheral nerve involvement in ADCA manifests not only as distal
      axonal neuropathy, but also as primary neuronopathy. Electrodiagnostic studies in
      this group of patients should be conducted in such a way that primary
      neuronopathy is detected.

PMID- 14967776
TI  - Left hemicranial hypoplasia in 2 patients with primary progressive aphasia.
AB  - BACKGROUND: Primary progressive aphasia (PPA) leads to a gradual and relatively
      isolated dissolution of language function. The factors that determine the
      selectivity of the disease process remain unknown. We had speculated that PPA may
      occasionally arise as a tardive manifestation of genetic or acquired
      vulnerabilities involving the language network of the brain. OBJECTIVE: To
      explore predisposing factors for PPA. RESULTS: In 2 patients, PPA developed with
      a background of mild left hemicranial hypoplasia. CONCLUSION: In keeping with
      other observations of PPA in patients with dyslexia and childhood injury to the
      left temporal lobe, these 2 patients support the contention that some cases of
      PPA may arise in settings where the language network has become a locus of least
      resistance.

PMID- 14967777
TI  - Revelation of a new mitochondrial DNA mutation (G12147A) in a MELAS/MERFF
      phenotype.
AB  - BACKGROUND: A 26-year-old man presented at onset with the syndrome of
      mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS)
      and later with a phenotype for MELAS and myoclonic epilepsy and ragged red fiber
      disease (MELAS/MERRF). OBJECTIVE: To identify the possible defects in the
      mitochondrial genome in blood and muscle samples of the patient. DESIGN: Case
      study of a patient clinically exhibiting strokelike episodes and then epilepsy
      with myoclonic features, ataxia, and dementia. SETTING: Research unit of a
      university hospital. MAIN OUTCOME MEASURES: Electromyographic, morphologic, and
      biochemical studies of muscle and molecular analysis of blood and muscle to
      investigate mitochondrial DNA (mtDNA) size and quantity. RESULTS:
      Morphologically, we found abnormal mitochondrial proliferation with several
      cytochrome-c oxidase (COX)-negative fibers in muscle biopsy specimens; the
      analysis of serial sections showed a decreased immunoreactivity for the mtDNA
      encoded subunits COXII and, partially, COXI. Biochemically, we found a partial
      and isolated COX deficiency. The complete mtDNA sequence analysis identified 3
      sequence changes, 2 of which were reported polymorphisms. The remaining change, a
      G12147A transition in the transfer RNA(His) gene, appeared to be the likely
      pathogenic mutation. CONCLUSIONS: Our data propose that the G12147A change, the
      first mutation in the transfer RNA(His) gene associated with an overlapped
      MELAS/MERFF phenotype, is the cause of the encephalomyopathy in this patient
      interfering with the overall mitochondrial protein synthesis.

PMID- 14967778
TI  - Impaired volitional closure of the left eyelid after right anterior cerebral
      artery infarction: apraxia due to interhemispheric disconnection?
AB  - BACKGROUND: The inability of volitional unilateral eyelid closure is an uncommon
      symptom of a central nervous system disorder. When it occurs as the result of a
      localized brain lesion, it is debated to be a form of supranuclear facial palsy
      or an apraxic phenomenon. OBJECTIVES: To report and discuss a unilateral (left
      sided) higher-order movement disorder of the facial periocular musculature
      bearing apraxic features. SETTING: University neurology department. PATIENT: A 78
      year-old right-handed man was admitted to the hospital with a left-sided
      brachiofacial hemiparesis of sudden onset. After thrombolysis with intravenous
      recombinant tissue-type plasminogen activator, the hemiparesis, including the
      left-sided facial weakness, disappeared. Serial computed tomographic scans showed
      that the patient was left with a stroke in the right anterior cerebral artery
      territory, affecting the frontal commissural fibers of the corpus callosum. There
      were no signs of upper motor neuron facial paresis on the left side when
      gesturing in a natural context. Eyelid closure was complete during sleep.
      However, left eyelid closure and elevation of the left eyebrow were not possible
      on verbal command. In contrast, voluntary innervation of the perioral facial
      musculature was performed properly. CONCLUSIONS: The voluntary-automatic
      dissociation of our patient's eyelid closure was suggestive of an apraxic
      disorder. Disconnection from a praxis center caused by callosal damage may be
      assumed to be the underlying cause. The unilaterality of the symptom might imply
      that in a bilaterally organized corticonuclear system such as upper face
      innervation, it is the crossing fibers that are primarily involved in praxis
      tasks.

PMID- 14967779
TI  - Tectal fourth nerve palsy due to infarction.

PMID- 14967780
TI  - Extensive intracranial bilateral symmetrical calcification secondary to
      hypoparathyroidism.

PMID- 14967781
TI  - The Monakow concept of diaschisis: origins and perspectives.
AB  - The idea that damage to one part of the nervous system can have effects at a
      distance was popular during the 19th century. Constantin von Monakow, MD,
      accepted this idea and blended it with the newly formulated neuron doctrine early
      in the 20th century to account for ipsilateral paralyses and recovery of
      function. He called his theory of neural depression caused by loss of inputs to
      structures tied to the damaged area diaschisis. In this article, we examine the
      origins of diaschisis and the goals of Monakow. Credit is given to Monakow for
      drawing needed attention to the dynamics of the nervous system, remote lesion
      effects, and recovery of function, even though the fine details or specifics of
      his theory have had a mixed reception.

PMID- 14967782
TI  - Alien hand syndrome.
AB  - In Stanley Kubrick's movie Dr Strangelove, the main character is described as
      "erratic" and displays a bizarre movement disorder. His right hand seems to be
      driven by a will of its own, at times clutching his own throat and at other times
      raising into a Nazi salute. Dr Strangelove must try to restrain this wayward limb
      with his left hand. Bizarre as this fictional character is, a similar movement
      disorder can occur in neurologic disease. The complex phenomenon associated with
      this disorder falls under the rubric of alien hand syndrome. This syndrome is
      characterized by a limb that seems to perform meaningful acts without being
      guided by the intention of the patient. Patients find themselves unable to stop
      the alien limb from reaching and grabbing objects, and they may be unable to
      release these grasped objects without using their other hand to pry open their
      fingers. These patients frequently express astonishment and frustration at the
      errant limb. They experience it as being controlled by an external agent and
      often refer to it in the third person. This article outlines the origins of the
      terminology used in describing this syndrome, early observations, and studies
      regarding its functional neuroanatomy.

PMID- 14967783
TI  - Carotid endarterectomy: turning up the volume?

PMID- 14967784
TI  - Reduced N-acetylaspartate levels and cognitive decline.

PMID- 14967785
TI  - Comments on neurological aspects of taste disorders.

PMID- 14967786
TI  - A semisynthetic bilaminar skin substitute used to treat pediatric full-body toxic
      epidermal necrolysis: wraparound technique in a 17-month-old girl.

PMID- 14967787
TI  - Group B streptococcal toxic shock-like syndrome.

PMID- 14967788
TI  - Number of satellite nevi as a correlate for neurocutaneous melanocytosis in
      patients with large congenital melanocytic nevi.
AB  - BACKGROUND: Patients with large congenital melanocytic nevi (LCMN) are at risk
      for neurocutaneous melanocytosis (NCM). Patients with LCMN on the posterior axis
      or in conjunction with many satellite melanocytic nevi seem to represent
      subgroups at greatest risk. OBJECTIVE: To determine the relationship between LCMN
      location, number of satellite nevi, and risk of NCM. DESIGN: Descriptive survey
      study. SETTING: An Internet Web-based registry of patients with LCMN, maintained
      by a nevus support group (Nevus Outreach Inc). PARTICIPANTS: Individuals with
      LCMN or their guardians visiting the Nevus Outreach Web site were provided the
      opportunity to complete the questionnaire. OUTCOME MEASURES: Location of LCMN,
      number of satellite nevi, and NCM as assessed by patient self-report. RESULTS: A
      total of 379 patients with LCMN were evaluated, 26 of whom had NCM. A
      significantly higher percentage of patients with NCM had their LCMN on the
      posterior axis compared with patients without NCM (96% and 70%, respectively).
      Patients with NCM had significantly more satellite melanocytic nevi compared with
      non-NCM patients (median, 68.5 and 18, respectively). Furthermore, patients with
      LCMN and more than 20 satellites had a 5.1-fold (95% confidence interval, 1.9
      14.0) increased risk for NCM compared with LCMN patients with 20 or fewer
      satellites. Logistic regression analysis, controlling for age, sex, number of
      satellite nevi, and LCMN location, identified number of satellite nevi as the
      only significant risk factor for NCM. CONCLUSIONS: The presence of large numbers
      of satellite nevi is the most important risk factor for NCM in patients with
      LCMN. Although location of the LCMN on the posterior axis was a moderate risk
      factor for NCM in univariate analysis, the strength of the relationship was
      attenuated in the multivariate analysis.

PMID- 14967789
TI  - Elliptical excisions: variations and the eccentric parallelogram.
AB  - BACKGROUND: The elliptical (fusiform) excision is a basic tool of cutaneous
      surgery. OBJECTIVE: To assess the design, functionality, ease of construction,
      and aesthetic outcomes of the ellipse. DESIGN: A systematic review of elliptical
      designs and their site-specific benefits and limitations. In particular, we
      consider the (1). context of prevailing relaxed skin tension lines and tissue
      laxity; and (2). removal of the smallest possible amount of tissue around the
      lesion and in the "dog-ears." Attention is focused on intuitive methods that can
      be reproducibly planned and executed. RESULTS: Elliptical variations are easily
      designed and can be adapted to many situations. The eccentric parallelogram
      excision is offered as a new technique that minimizes notching and focal tension
      in the center of an elliptical closure. Conclusion The elliptical (fusiform)
      excision is an efficient, elegant, and versatile technique that will remain a
      mainstay of the cutaneous surgical armamentarium.

PMID- 14967790
TI  - Association between anticonvulsant hypersensitivity syndrome and human
      herpesvirus 6 reactivation and hypogammaglobulinemia.
AB  - BACKGROUND: Anticonvulsant hypersensitivity syndrome (AHS) is a life-threatening,
      drug-induced, multiorgan system reaction. The identification of predisposing
      factors is clearly needed to predict the incidence and outcome of AHS; attention
      has recently been focused on reactivation of human herpesvirus 6 (HHV-6).
      OBJECTIVE: To determine whether immunosuppressive conditions that can allow HHV-6
      reactivation could be specifically detected in association with the onset of AHS.
      DESIGN: We analyzed patients with AHS who were treated during 1997-2002. Two
      groups of patients receiving anticonvulsants served as controls. SETTING:
      Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan.
      Patients Ten patients with AHS. MAIN OUTCOME MEASURES: The results of serologic
      tests for antibody titers for various viruses, including HHV-6, HHV-6 DNA
      detection by real-time polymerase chain reaction, immunoglobulin levels by
      turbidimetric immunoassay, IgG subclass levels by nephelometry, and CD19(+) B
      cell counts by flow cytometric analysis, were sequentially assessed. RESULTS:
      Serum IgG levels (mean, 745 mg/dL) and circulating B-cell counts (mean, 88/ micro
      L) in patients with AHS were significantly decreased at onset compared with
      control groups (P<.001 and P =.007, respectively). These alterations returned to
      normal on full recovery. Reactivation of HHV-6 as judged by a greater than 4-fold
      increase in HHV-6 IgG titers was exclusively detected in most patients with AHS
      associated with decreased IgG levels and B-cell counts. CONCLUSIONS: A decrease
      in immunoglobulin levels and B-cell counts can be associated with HHV-6
      reactivation and the subsequent onset of AHS. These immunological alterations
      might be a useful predictor of the development of AHS.

PMID- 14967791
TI  - Gender and parenting significantly affect work hours of recent dermatology
      program graduates.
AB  - BACKGROUND: The increased proportion of female physicians over the last 30 years
      may have important implications for future physician workforce needs. OBJECTIVE:
      To assess the roles of gender, marital status, and parenting in employment
      choices. DESIGN, SETTING, AND PARTICIPANTS: Anonymous surveys were distributed to
      recent dermatology residency graduates taking a board examination review course
      from 1999 through 2002. MAIN OUTCOME MEASURES: The number of hours respondents
      saw patients per week and the number of hours they spent in each field of
      dermatology per week. RESULTS: There were 191 respondents to the survey in 2002,
      which represented 54% of the 2002 residency graduates. For clarity, this article
      focuses on the 2002 results except where trends over time become apparent. Of the
      respondents, 57% were women and 43% were men. Women saw patients a mean of 26
      hours per week while men saw patients a mean of 31 hours (P =.01), although women
      spent more time practicing medical dermatology. Marital status did not
      significantly affect the number of work hours. Men and women who were not parents
      worked almost the same number of hours per week, but male parents saw patients a
      greater number of hours than female parents (34 vs 24; P<.01). Men who were
      parents spent more hours per week seeing patients than men who were not. In
      contrast, women who were parents spent fewer hours seeing patients than women who
      were not.Conclusion Parenting, in combination with gender, greatly influences
      workforce choices for professionals with young families while gender alone has
      little impact on those choices.

PMID- 14967793
TI  - UV radiation exposure related to age, sex, occupation, and sun behavior based on
      time-stamped personal dosimeter readings.
AB  - OBJECTIVE: To assess individual time-related (time-stamped) UV radiation (UVR)
      dose pattern and sun exposure behavior. DESIGN: Open prospective observational
      study. SETTING: University hospital. Study Subjects Two hundred eighty-five
      Danish volunteers with apparently healthy skin: children, adolescents, indoor
      workers, sun worshippers, golfers, and gardeners (age range, 4-68 years).
      Measurements We developed a personal electronic UVR dosimeter in a wristwatch
      (SunSaver) and measured continuously time-related UVR doses in standard erythema
      dose (SED) and corresponding sun exposure behavior from diaries, resulting in 346
      sun-years (median, 119 days). The estimated yearly UVR doses were calculated
      based on personal and ambient measured doses. RESULTS: The median estimated
      yearly UVR dose was 173 SEDs (range, 132 SEDs [indoor workers]-224 SEDs
      [gardeners]), with no significant difference by age (P =.25) or sex (P =.75). The
      SED of girls (175 SEDs) was significantly (P =.04) higher than that of boys (116
      SEDs). Subjects younger than 20 years had an increase of 5 SEDs per year (P
      =.03). Sunbathing or exposing shoulders (risk behavior) outside the beach
      resulted in a median of 2.5 SEDs per day in northern Europe and 3.2 SEDs per day
      in southern Europe; however, at the beach, corresponding values were 4.6 and 6.9
      SEDs per day. Children and adolescents received more than half their total UVR
      dose at the beach. Sunburning doses above 10 SEDs per day were connected with
      sunbathing or exposing shoulders. Of the UVR dose, 50% was received between noon
      and 3 PM. Only the gardeners received most of their UVR dose (55%) on working
      days. CONCLUSIONS: High UVR doses are connected with risk behavior, except for
      outdoor workers. There is no need to change sun exposure habits on days without
      risk behavior.

PMID- 14967794
TI  - Histological and ultrastructural evaluation of the effects of a radiofrequency
      based nonablative dermal remodeling device: a pilot study.
AB  - BACKGROUND: Many light- and laser-based systems are used to reduce cutaneous
      wrinkles, and some have been shown to stimulate dermal collagen production. Using
      the ThermaCool TC radiofrequency device to treat bovine tendon and human
      abdominal skin, we documented the cutaneous effects of a radiofrequency-based
      system for nonablative treatment. OBSERVATIONS: Electron microscopy of bovine
      tendon treated at varied heat and cooling settings revealed collagen fibrils with
      increased diameter and loss of distinct borders as deep as 6 mm. Human skin
      treated at varied heat and cooling settings and examined by means of routine
      light microscopy demonstrated no significant changes in the epidermis or dermal
      ground substance immediately after treatment; there was scattered mild
      perivascular and periadnexal inflammation. Three and 8 weeks after treatment, no
      observable changes were noted. Ultrastructural analysis, however, disclosed
      isolated, scattered areas of collagen fibrils with increased diameter and loss of
      distinct borders. In addition, Northern blot analysis demonstrated an increase in
      collagen type I messenger RNA steady-state expression. CONCLUSIONS: Our findings
      suggest that collagen fibril contraction occurs immediately after treatment and
      gives rise to tissue contraction and thermally mediated wounding, which induces
      new collagen production.

PMID- 14967796
TI  - Propionibacterium acnes and the pathogenesis of progressive macular
      hypomelanosis.
AB  - BACKGROUND: Progressive macular hypomelanosis is a common hypopigmentation mainly
      on the central parts of the trunk, predominantly in young adults, especially
      women. It is often mistaken for pityriasis versicolor and pityriasis alba. It
      occurs in all races and has been described in many parts of the world. We
      discovered follicular red fluorescence restricted to lesional skin. We suspected
      a relation with a porphyrin-producing bacteria residing in sebum of the
      pilosebaceous duct, and we therefore performed a study in 8 patients. Observation
      In all biopsy specimens taken from lesional skin of 8 women, we could demonstrate
      gram-positive bacteria in the pilosebaceous duct, and a mild perifollicular
      lymphocytic infiltrate was seen. In all but 1 patient, Propionibacterium acnes
      was yielded from cultured biopsy specimens taken from follicular lesional skin.
      Healthy follicular skin did not show bacteria in histological sections, and
      cultures did not yield anaerobic bacteria. CONCLUSIONS: There seems to be a
      relation between the presence of P acnes and the hypopigmented macules. We
      propose that a factor is produced by these strains of P acnes, which interfere
      with melanogenesis. Based on these observations, we are undertaking a clinical
      trial to find a treatment for this troubling, intractable disease.

PMID- 14967798
TI  - Severe, generalized nummular eczema secondary to interferon alfa-2b plus
      ribavirin combination therapy in a patient with chronic hepatitis C virus
      infection.
AB  - BACKGROUND: With increasing rates of hepatitis C virus infection and diagnosis,
      more patients are being treated with interferon alfa-2b plus ribavirin therapy.
      Cutaneous side effects to combination therapy are common and may limit treatment.
      There are few previous case reports of generalized eczematous dermatoses
      occurring after combination therapy for hepatitis C virus, none in a North
      American patient, and none of this severity or recalcitrance. OBSERVATIONS: A man
      with chronic hepatitis C virus infection and no history of atopy developed
      severe, recalcitrant nummular eczema secondary to interferon alfa-2b plus
      ribavirin combination therapy. The cutaneous side effect was more severe than in
      previously reported cases and did not remit on discontinuation of therapy.
      CONCLUSIONS: Greater awareness of the range of dermatologic responses to
      interferon alfa-2b plus ribavirin therapy may lead to improved surveillance for
      and treatment of these side effects. Investigating the underlying pathologic
      mechanisms may ultimately allow for a greater understanding of the
      immunomodulatory effects of this therapy in the setting of chronic hepatitis C
      virus infection.

PMID- 14967799
TI  - Potential of tumor necrosis factor inhibitors in psoriasis and psoriatic
      arthritis.
AB  - OBJECTIVES: To summarize the role of tumor necrosis factor (TNF) in the
      pathogenesis of psoriasis and psoriatic arthritis (PsA) and to present the latest
      data on the efficacy of TNF inhibitors in these diseases. DATA SOURCES: PubMed
      was used with the following indexing terms: TNF, TNF inhibitor, psoriasis,
      psoriatic arthritis, etanercept, infliximab, and/or T cell. Abstract booklets and
      manufacturer's package inserts were also used. When possible, only sources
      published after the year 2000 were incorporated. STUDY SELECTION: Sources that
      described a role for TNF in the pathogenesis of psoriasis and PsA were selected
      based on relevance. Clinical trials that examined the efficacy of the TNF
      inhibitors etanercept and infliximab in psoriasis and PsA were selected. DATA
      EXTRACTION: Data were extracted if they represented safety information, the
      American College of Rheumatology criteria for improvement, the Health Assessment
      Questionnaire, or the PsA response criteria. These data were abstracted
      independently by the authors. DATA SYNTHESIS: Aberrant regulation of TNF is
      involved in the development of psoriasis and PsA. Therefore, recent intervention
      strategies for psoriasis and PsA have incorporated biologic agents that
      specifically target TNF. Etanercept and infliximab are effective at reducing
      disease activity and are generally well tolerated in the treatment of psoriasis
      and PsA. CONCLUSION: Tumor necrosis factor plays a major role in the pathogenesis
      of psoriasis and PsA, and TNF antagonists provide clinicians with a worthy
      alternative to traditional therapies, which are associated with toxic effects and
      poor compliance.

PMID- 14967800
TI  - Is a drug alone sufficient to cause the drug hypersensitivity syndrome?

PMID- 14967801
TI  - A 10-week-old boy with a telangiectatic nodule on the knee--quiz case.

PMID- 14967802
TI  - Vesicular eruption on the trunk and in intertriginous folds--quiz case.

PMID- 14967803
TI  - Upper extremity nodules--quiz case.

PMID- 14967804
TI  - Multiple eyelid cysts with palmoplantar hyperkeratosis--quiz case.

PMID- 14967805
TI  - Sentinel lymph node biopsy in patients with thin melanoma.

PMID- 14967806
TI  - Sentinel lymph node biopsy: the issue of probability and statistics.

PMID- 14967807
TI  - Granulomatous rosacea affecting the lacrimal and salivary glands.

PMID- 14967808
TI  - Kinetics and specificity of fas ligand induction in toxic epidermal necrolysis.

PMID- 14967809
TI  - Dermoscopy of keratinocytic neoplasms: subpatterns of seborrheic keratoses.

PMID- 14967810
TI  - Integrating the genotype and phenotype in hominid paleontology.
AB  - Competing interpretations of human origins and evolution have recently
      proliferated despite the accelerated pace of fossil discovery. These
      controversies parallel those involving other vertebrate families and result from
      the difficulty of studying evolution among closely related species. Recent
      advances in developmental and quantitative genetics show that some conventions
      routinely used by hominid and other mammalian paleontologists are unwarranted.
      These same advances provide ways to integrate knowledge of the genotype into the
      study of the phenotype. The result is an approach that promises to yield a fuller
      understanding of evolution below the family level.

PMID- 14967811
TI  - The Barrett's antigen anterior gradient-2 silences the p53 transcriptional
      response to DNA damage.
AB  - The esophageal epithelium is subject to damage from bile acid reflux that
      promotes normal tissue injury resulting in the development of Barrett's
      epithelium. There is a selection pressure for mutating p53 in this preneoplastic
      epithelium, thus identifying a physiologically relevant model for discovering
      novel regulators of the p53 pathway. Proteomic technologies were used to identify
      such p53 regulatory factors by identifying proteins that were overexpressed in
      Barrett's epithelium. A very abundant polypeptide selectively expressed in
      Barrett's epithelium was identified as anterior gradient-2. Immunochemical
      methods confirmed that anterior gradient-2 is universally up-regulated in
      Barrett's epithelium, relative to normal squamous tissue derived from the same
      patient. Transfection of the anterior gradient-2 gene into cells enhances colony
      formation, similar to mutant oncogenic p53 encoded by the HIS175 allele,
      suggesting that anterior gradient-2 can function as a survival factor. Deletion
      of the C-terminal 10 amino acids of anterior gradient-2 neutralizes the colony
      enhancing activity of the gene, suggesting a key role for this domain in
      enhancing cell survival. Constitutive overexpression of anterior gradient-2 does
      not alter cell-cycle parameters in unstressed cells, suggesting that this gene is
      not directly modifying the cell cycle. However, cells overexpressing anterior
      gradient-2 attenuate p53 phosphorylation at both Ser(15) and Ser(392) and silence
      p53 transactivation function in ultraviolet (UV)-damaged cells. Deletion of the C
      terminal 10 amino acids of anterior gradient-2 permits phosphorylation at Ser(15)
      in UV-damaged cells, suggesting that the C-terminal motif promoting colony
      survival also contributes to suppression of the Ser(15) kinase pathway. These
      data identify anterior gradient-2 as a novel survival factor whose study may shed
      light on cellular pathways that attenuate the tumor suppressor p53.

PMID- 14967812
TI  - Apolipoprotein A-II regulates HDL stability and affects hepatic lipase
      association and activity.
AB  - The effect of apolipoprotein A-II (apoA-II) on the structure and stability of HDL
      has been investigated in reconstituted HDL particles. Purified human apoA-II was
      incorporated into sonicated, spherical LpA-I particles containing apoA-I,
      phospholipids, and various amounts of triacylglycerol (TG), diacylglycerol (DG),
      and/or free cholesterol. Although the addition of PC to apoA-I reduces the
      thermodynamic stability (free energy of denaturation) of its alpha-helices, PC
      has the opposite effect on apoA-II and significantly increases its helical
      stability. Similarly, substitution of apoA-I with various amounts of apoA-II
      significantly increases the thermodynamic stability of the particle alpha-helical
      structure. ApoA-II also increases the size and net negative charge of the
      lipoprotein particles. ApoA-II directly affects apoA-I conformation and increases
      the immunoreactivity of epitopes in the N and C termini of apoA-I but decreases
      the exposure of central domains in the molecule (residues 98-186). ApoA-II
      appears to increase HL association with HDL and inhibits lipid hydrolysis. ApoA
      II mildly inhibits PC hydrolysis in TG-enriched particles but significantly
      inhibits DG hydrolysis in DG-rich LpA-I. In addition, apoA-II enhances the
      ability of reconstituted LpA-I particles to inhibit VLDL-TG hydrolysis by HL.
      Therefore, apoA-II affects both the structure and the dynamic behavior of HDL
      particles and selectively modifies lipid metabolism.

PMID- 14967813
TI  - Alteration in lipoprotein lipase activity bound to triglyceride-rich lipoproteins
      in the postprandial state in type 2 diabetes.
AB  - Postprandial lipid metabolism is largely dependent upon lipoprotein lipase (LPL),
      which hydrolyses triglycerides (TGs). The time course of LPL activity in the
      postprandial state following a single meal has never been studied, because its
      determination required heparin injection. Recently, we have shown that LPL
      activity could be accurately measured in nonheparinized VLDL using a new assay
      aiming to determine the LPL-dependent VLDL-TG hydrolysis. Based on the same
      principle, we used in this study TG-rich lipoprotein (TRL)-bound LPL-dependent
      TRL-TG hydrolysis (LTTH) to compare the time course of LPL activity of 10 type 2
      diabetics to that of 10 controls, following the ingestion of a lipid-rich meal.
      The peak TG concentration, reached after 4 h, was 67% higher in diabetics than in
      controls (P < 0.005). Fasting LTTHs were 91.3 +/- 15.6 in controls versus 70.1 +/
      4.8 nmol NEFA/ml/h in diabetics (P < 0.001). LTTH was increased 2 h
      postprandially by 190% in controls and by only 89% in diabetics, resulting in a
      35% lowering of the LTTH area under the curve in diabetics. Postprandial LTTH was
      inversely correlated with TG or remnant concentrations in controls but not in
      diabetics, and with insulin resistance in both groups. These data show that TRL
      bound LPL activity increases in the postprandial state and is strongly reduced in
      type 2 diabetes, contributing to postprandial hypertriglyceridemia.

PMID- 14967814
TI  - Increased production of VLDL apoB-100 in subjects with familial
      hypercholesterolemia carrying the same null LDL receptor gene mutation.
AB  - Early radiokinetic studies revealed that the classical metabolic defect in
      patients with familial hypercholesterolemia (FH) is hypocatabolism of LDL due to
      decreased LDL receptor activity. However, recent studies have suggested that
      hepatic oversecretion of apolipoprotein B-100 (apoB-100)-containing lipoproteins
      could also contribute to the markedly elevated plasma concentrations of LDL
      cholesterol found in FH. The aim of this study was to examine the kinetics of
      apoB-100 labeled with a stable isotope (l-[5,5,5-D(3)] leucine) in five
      normolipidemic controls and in seven well-characterized FH subjects that included
      six FH heterozygotes and one FH homozygote carrying the same null LDL receptor
      gene mutation. As compared with controls, the VLDL apoB-100 production rate was
      increased by 50% in the FH heterozygotes and by 109% in the FH homozygote.
      Furthermore, FH subjects had significantly higher LDL apoB-100 pool size and
      lower LDL apoB-100 fractional catabolic rate than controls. These results
      indicate that the elevation of plasma LDL-cholesterol found in FH is attributable
      to both decreased clearance of LDL and increased hepatic production of apoB-100
      containing lipoproteins.

PMID- 14967815
TI  - Oxidized LDL further enhances expression of adhesion molecules in Chlamydophila
      pneumoniae-infected endothelial cells.
AB  - Chlamydophila pneumoniae is a common respiratory pathogen that has been shown to
      be associated with coronary artery disease. Recent studies have shown that one of
      the possible mechanisms of the atherogenicity of C. pneumoniae is overexpression
      of cell adhesion molecules (CAMs) in infected endothelial cells. We investigated
      whether exposure of C. pneumoniae-infected endothelial cells to oxidized LDL
      (oxLDL) leads to further upregulation of CAMs. Flow cytometry and immunoblot
      analysis of human aortic endothelial cells (HAECs) was performed for
      intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
      (VCAM-1), and E-selectin. ICAM-1 was expressed in 78.7% of C. pneumoniae-infected
      HAECs. The addition of oxLDL (100 microg/ml) to infected HAECs increased the
      proportion of ICAM-1-positive cells to 92%. VCAM-1 was only observed in 9.3% of
      infected HAECs, and the addition of oxLDL had no further effect on the surface
      expression of VCAM-1. C. pneumoniae also upregulated the surface expression of E
      selectin on 52.2% of the cells, and incubation with oxLDL further increased the
      proportion of positive cells to 63.64%. In conclusion, C. pneumoniae upregulated
      the expression of the adhesion molecules ICAM-1, VCAM-1, and E-selectin on HAECs.
      The addition of oxLDL to the infected cells further enhanced the surface
      expression of ICAM-1 and E-selectin.

PMID- 14967816
TI  - Sterol regulation of scavenger receptor class B type I in macrophages.
AB  - Scavenger receptor class B type I (SR-BI) is expressed in macrophages, but its
      role in sterol trafficking in these cells remains controversial. We examined the
      effect of sterol loading on SR-BI expression in human monocytes/macrophages,
      mouse peritoneal macrophages, and a cultured mouse macrophage cell line (J774
      cells). Sterol loading using either acetylated LDL or 25-hydroxycholesterol
      resulted in a time- and concentration-dependent decrease in SR-BI protein and
      mRNA levels. Treatment of lipid-loaded J774 cells with cyclodextrin or HDL to
      promote cellular sterol efflux was associated with an increase in SR-BI
      expression. Studies were performed to determine if the sterol-associated
      downregulation of SR-BI in macrophages was mediated by either sterol regulatory
      element binding proteins (SREBPs) or the liver X receptor (LXR). Expression of
      constitutively active SREBPs failed to alter the expression of a luciferase
      reporter placed downstream of a 2556 bp 5' flanking sequence from the mouse SR-BI
      gene. Reduction in SR-BI expression was also seen in sterol-loaded peritoneal
      macrophages from mice expressing no LXRalpha and LXRbeta. We conclude that SR-BI
      levels in macrophages are responsive to changes in intracellular sterol content
      and that these sterol-associated changes are not mediated by LXR and are unlikely
      to be mediated by an SREBP pathway.

PMID- 14967817
TI  - Triglyceride levels are ethnic-specifically associated with an index of stearoyl
      CoA desaturase activity and n-3 PUFA levels in Asians.
AB  - Accumulated evidence suggests that hypertriglyceridemia (HTG) is independently
      associated with an increased incidence of cardiovascular disease. The
      hypotriglyceridemic effects of n-3 PUFAs have been confirmed in Caucasians, but
      the effect in Asians is less clear. Recent evidence indicates that stearoyl-CoA
      desaturase (SCD) activity induced with high-carbohydrate diets increases plasma
      triglyceride levels. We investigated the relationship between triglyceride levels
      and the ratio of plasma oleic acid to stearic acid (the 18:1/18:0 ratio), a
      plasma marker of SCD activity, and n-3 PUFAs in 411 Japanese, 418 Korean, and 251
      Mongolian adults. The Japanese and Koreans had higher values for triglyceride
      than their Mongolian counterparts, despite lower body mass index values for the
      Japanese and Koreans. The Japanese and Koreans ate fish more frequently and had
      remarkably higher values for n-3 PUFAs than did the Mongolians. Multiple
      regression analysis showed that triglyceride levels had a great magnitude of
      correlation with the increases in 18:1/18:0 ratio for the Japanese and
      Mongolians, and n-3 PUFAs remained significant for the Mongolians. HTG is
      ethnicity-specifically associated with an increase in the 18:1/18:0 ratio and a
      decrease in n-3 PUFA in plasma for Japanese, Koreans, and Mongolians.

PMID- 14967818
TI  - Novel lipid mixtures based on synthetic ceramides reproduce the unique stratum
      corneum lipid organization.
AB  - Lipid lamellae present in the outermost layer of the skin protect the body from
      uncontrolled water loss. In human stratum corneum (SC), two crystalline lamellar
      phases are present, which contain mostly cholesterol, free fatty acids, and nine
      types of free ceramides. Previous studies have demonstrated that the SC lipid
      organization can be mimicked with model mixtures based on isolated SC lipids.
      However, those studies are hampered by low availability and high interindividual
      variability of the native tissue. To elucidate the role of each lipid class in
      the formation of a competent skin barrier, the use of synthetic lipids would
      offer an alternative. The small- and wide-angle X-ray diffraction results of the
      present study show for the first time that synthetic lipid mixtures, containing
      only three synthetic ceramides, reflect to a high extent the SC lipid
      organization. Both an appropriately chosen preparation method and lipid
      composition promote the formation of two characteristic lamellar phases with
      repeat distances similar to those found in native SC. From all synthetic lipid
      mixtures examined, equimolar mixtures of cholesterol, ceramides, and free fatty
      acids equilibrated at 80 degrees C resemble to the highest extent the lamellar
      and lateral SC lipid organization, both at room and increased temperatures.

PMID- 14967819
TI  - Oligonucleotides blocking glucosylceramide synthase expression selectively
      reverse drug resistance in cancer cells.
AB  - High glucosylceramide synthase (GCS) activity is one factor contributing to
      multidrug resistance (MDR) in breast cancer. Enforced GCS overexpression has been
      shown to disrupt ceramide-induced apoptosis and to confer resistance to
      doxorubicin. To examine whether GCS is a target for cancer therapy, we have
      designed and tested the effects of antisense oligodeoxyribonucleotides (ODNs) to
      GCS on gene expression and chemosensitivity in multidrug-resistant cancer cells.
      Here, we demonstrate that antisense GCS (asGCS) ODN-7 blocked cellular GCS
      expression and selectively increased the cytotoxicity of anticancer agents.
      Pretreatment with asGCS ODN-7 increased doxorubicin sensitivity by 17-fold in MCF
      7-AdrR (doxorubicin-resistant) breast cancer cells and by 10-fold in A2780-AD
      (doxorubicin-resistant) ovarian cancer cells. In MCF-7 drug-sensitive breast
      cancer cells, asGCS ODN-7 only increased doxorubicin sensitivity by 3-fold, and
      it did not influence doxorubicin cytotoxicity in normal human mammary epithelial
      cells. asGCS ODN-7 was shown to be more efficient in reversing drug resistance
      than either the GCS chemical inhibitor d-threo-1-phenyl-2-decanoylamino-3
      morpholino-1-propanol or the P-glycoprotein blocking agents verapamil and
      cyclosporin A. Experiments defining drug transport and lipid metabolism
      parameters showed that asGCS ODN-7 overcomes drug resistance mainly by enhancing
      drug uptake and ceramide-induced apoptosis. This study demonstrates that a 20-mer
      asGCS oligonucleotide effectively reverses MDR in human cancer cells.

PMID- 14967820
TI  - Fatty liver in familial hypobetalipoproteinemia: roles of the APOB defects, intra
      abdominal adipose tissue, and insulin sensitivity.
AB  - Fatty liver is frequent in the apolipoprotein B (apoB)-defective genetic form of
      familial hypobetalipoproteinemia (FHBL), but interindividual variability in liver
      fat is large. To explain this, we assessed the roles of metabolic factors in 32
      affected family members with apoB-defective FHBL and 33 related and unrelated
      normolipidemic controls matched for age, sex, and indices of adiposity. Two hour,
      75 g oral glucose tests, with measurements of plasma glucose and insulin levels,
      body mass index, and waist-hip ratios were obtained. Abdominal subcutaneous,
      intraperitoneal (IPAT), and retroperitoneal adipose tissue masses were quantified
      by MR imaging, and hepatic fat was quantified by MR spectroscopy. Mean +/- SD
      liver fat percentage values of FHBL and controls were 14.8 +/- 12.0 and 5.2 +/-
      5.9, respectively (P = 0.001). Means for these measures of obesity and insulin
      action were similar in the two groups. Important determinants of liver fat
      percentage were FHBL-affected status, IPAT, and area under the curve (AUC)
      insulin in both groups, but the strongest predictors were IPAT in FHBL (partial
      R(2) = 0.55, P < 0.0002) and AUC insulin in controls (partial R(2) = 0.59, P =
      0.0001). Regression of liver fat percentage on IPAT fat was significantly greater
      for FHBL than for controls (P < 0.001). In summary, because apoB-defective FHBL
      imparts heightened susceptibility to liver triglyceride accumulation, increasing
      IPAT and insulin resistance exert greater liver fat-increasing effects in FHBL.

PMID- 14967821
TI  - A prospective study of HDL-C and cholesteryl ester transfer protein gene
      mutations and the risk of coronary heart disease in the elderly.
AB  - High density lipoprotein cholesterol (HDL-C) levels are inversely associated with
      the incidence of coronary heart disease (CHD) in middle-aged individuals; in the
      elderly, the association is less clear. Genetic factors, including variations in
      the cholesteryl ester transfer protein (CETP) gene, play a role in determining
      HDL-C levels. Controversy remains about whether CETP deficiency and the resultant
      rise in HDL-C are antiatherogenic, or whether CETP has the opposite effect due to
      its role in reverse cholesterol transport. In a seven-year follow-up of 2340 men
      aged 71-93 in the Honolulu Heart Program, the age-adjusted CHD incidence rates
      were significantly lower in men with high versus low HDL-C levels. After
      adjustment for age, hypertension, smoking, and total cholesterol, the relative
      risk of CHD for those with HDL-C levels >or=60 mg/dl, compared with those with
      HDL-C levels <40 mg/dl, was 0.6. Men with a CETP mutation had the lowest rates of
      CHD, although this was not statistically significant. These data indicate that
      HDL-C remains an important risk factor for CHD in the elderly. Whether a CETP
      mutation offers additional protection against CHD warrants further investigation.

PMID- 14967822
TI  - Combined data from LDL composition and size measurement are compatible with a
      discoid particle shape.
AB  - The size of LDL is usually reported as particle diameter, with the implicit
      assumption that it is a spherical particle. On the other hand, data obtained by
      cryoelectron microscopy and crystallographic analysis suggest that LDL shape may
      be discoid. We have investigated LDL particle geometry by combining data on LDL
      lipid composition with size measurement. The mean LDL diameter of 160 samples was
      measured by high-performance gel-filtration chromatography (HPGC), and particle
      volume was calculated from its lipid composition. Assuming a spherical shape,
      diameters calculated from volume correlated poorly with values obtained by HPGC
      (R(2) = 0.36). Assuming a discoid shape, particle height was calculated from
      volume and HPGC diameter. Diameter (20.9 +/- 0.5 nm) and height (12.1 +/- 0.8 nm)
      were not significantly related to each other (r = 0.14, P = 0.09) and accounted
      for 23% and 77%, respectively, of the variation in particle volume. In
      multivariate regression models, LDL core lipids were the main determinants of
      height (R(2) = 0.83), whereas free cholesterol in the shell, which contributes
      only 5-9% to LDL mass, was the main determinant of diameter (R(2) = 0.54). We
      conclude that combined data from composition and size measurements are compatible
      with a discoid particle shape and propose a structural model for LDL in which
      free cholesterol plays a major role in determining particle shape and diameter.

PMID- 14967823
TI  - LXR-mediated activation of macrophage stearoyl-CoA desaturase generates
      unsaturated fatty acids that destabilize ABCA1.
AB  - Abnormal HDL metabolism among patients with diabetes and insulin resistance may
      contribute to their increased risk of atherosclerosis. ATP binding cassette
      transporter A1 (ABCA1) mediates the transport of cholesterol and phospholipids
      from cells to HDL apolipoproteins and thus modulates HDL levels and
      atherogenesis. Because fatty acids are increased in diabetes, we examined their
      effects on ABCA1 activity in cultured macrophages. cAMP analogs and ligands for
      the liver X receptor/retinoid X receptor (LXR/RXR) system can induce Abca1
      transcription in murine macrophages. When induced by cAMP, unsaturated but not
      saturated long-chain fatty acids inhibit apolipoprotein-mediated lipid efflux by
      destabilizing ABCA1 protein. Here, we show that the saturated fatty acids
      palmitate and stearate also destabilize ABCA1 when Abca1 is induced by LXR/RXR
      ligands instead of cAMP. This was associated with increased palmitate and
      stearate desaturation by stearoyl-CoA desaturase (SCD), another gene product
      induced by LXR/RXR ligands. The SCD inhibitors conjugated linoleic acid and
      troglitazone nearly abolished ABCA1 destabilization by palmitate and stearate but
      not by linoleate. These results suggest that LXR/RXR ligands generate ABCA1
      destabilizing monounsaturated fatty acids from their saturated precursors by
      activating SCD. Thus, with cholesterol-loaded macrophages exposed to saturated
      fatty acids, activated LXR/RXR may counteract the enhanced ABCA1 transcription by
      reducing the ABCA1 protein content.

PMID- 14967824
TI  - Sterol and fatty acid regulatory pathways in a Giardia lamblia-derived promoter:
      evidence for SREBP as an ancient transcription factor.
AB  - The sterol regulatory element binding-proteins (SREBPs) are transcription factors
      that regulate the genes of lipid metabolism. Cholesterol and unsaturated fatty
      acids regulate SREBPs. Giardia lamblia (GL) is an intestinal parasite and one of
      the earliest derived members within the eukaryotic lineage. GLs exist as
      trophozoites and cysts. Growth in cholesterol depletion induces transcription of
      cyst-wall protein (CWP) genes that are upregulated during encystation. The
      hypothesis was investigated that SREBP-like pathways have a role in cwp gene
      transcription. Chinese hamster ovary cells were transfected with a cwp-2 promoter
      reporter construct. Incubation with cholesterol or oleate reduced cwp-2 mediated
      gene transcription to about half of the control. Incubation in sterol-depleted
      media, or in the presence of either an inhibitor of intracellular cholesterol
      movement or inhibitor of cholesterol synthesis, increased gene expression up to 3
      fold. Overexpression of SREBPs increased reporter gene activity 2.5-fold. In the
      absence of functional SREBPs, cwp-2 was not regulated by cholesterol. Footprint
      analysis of cwp-2 reveals three novel binding sites for mammalian SREBPs with no
      homologies in other species or humans. The data show that SREBP binds to and can
      modulate transcription of a regulatory element from an ancient eukaryote and
      suggest the existence of an SREBP homolog in GL.

PMID- 14967825
TI  - Human S100B protein interacts with the Escherichia coli division protein FtsZ in
      a calcium-sensitive manner.
AB  - S100B is a small, dimeric EF-hand calcium-binding protein abundant in
      vertebrates. Upon calcium binding, S100B undergoes a conformational change
      allowing it to interact with a variety of target proteins, including the
      cytoskeletal proteins tubulin and glial fibrillary acidic protein. In both cases,
      S100B promotes the in vitro disassembly of these proteins in a calcium-sensitive
      manner. Despite this, there is little in vivo evidence for the interaction of
      proteins such as tubulin with S100B. To probe these interactions, we studied the
      expression of human S100B in Escherichia coli and its interaction with the
      prokaryotic ancestor of tubulin, FtsZ, the major protein involved in bacterial
      division. Expression of S100B protein in E. coli results in little change in FtsZ
      protein levels, causes a filamenting bacterial phenotype characteristic of FtsZ
      inhibition, and leads to missed rounds of cell division. Further, S100B localizes
      to positions similar to those of FtsZ in bacterial filaments: the small foci at
      the poles, the mid-cell positions, and between the nucleoids at regular
      intervals. Calcium-dependent physical interaction between S100B and FtsZ was
      demonstrated in vitro by affinity chromatography, and this interaction was
      severely inhibited by the competitor peptide TRTK-12. Together these results
      indicate that S100B interacts with the tubulin homologue FtsZ in vivo, modulating
      its activity in bacterial cell division. This approach will present an important
      step for the study of S100 protein interactions in vivo.

PMID- 14967826
TI  - Effect of caffeine on blood pressure beyond the laboratory.

PMID- 14967827
TI  - Blood pressure response to caffeine shows incomplete tolerance after short-term
      regular consumption.
AB  - Caffeine acutely raises blood pressure (BP). The clinical significance of this
      effect depends on whether BP responses persist in persons who consume caffeine on
      a daily basis. Accordingly, the ability of caffeine to raise BP after 5 days of
      regular daily intake was tested in a randomized controlled trial. Individual
      differences in tolerance formation were then examined. Men (n=49) and women
      (n=48) completed a double-blind, crossover trial conducted over 4 weeks. During
      each week, subjects abstained for 5 days from dietary caffeine and instead used
      capsules totaling 0 mg, 300 mg, and 600 mg of caffeine per day in 3 divided
      doses. On day 6, in the laboratory, they used capsules with either 0 mg or 250 mg
      of caffeine at 9:00 am and 1:00 pm. Systolic/diastolic BP increases as a result
      of 250 mg of caffeine remained significant (P<0.006/0.001) at all levels of
      previous daily consumption. Individual difference comparisons found that although
      half the subjects had complete loss of systolic and diastolic BP responses to the
      challenge doses, the other half showed no loss in BP response, even after using
      600 mg of caffeine per day for the previous 5 days (F >7.90, P <0.001). The sexes
      did not differ in degree of tolerance formation. Daily caffeine consumption
      failed to eliminate the BP response to repeated challenge doses of caffeine in
      half of the healthy adults who were tested. Caffeine may therefore cause
      persistent BP effects in persons who are regular consumers, even when daily
      intake is at moderately high levels.

PMID- 14967828
TI  - How does angiotensin II cause renal injury?

PMID- 14967829
TI  - Angiotensin II and cell cycle regulation.
AB  - Angiotensin II has emerged as an important growth factor for vascular, cardiac,
      and renal cells. Depending on the specific cell type and presence of other growth
      factors, angiotensin II induces proliferation (replication of DNA with subsequent
      successful division of cells), hypertrophy (increase in cell size, cell protein,
      and mRNA content without DNA replication), apoptosis (programmed cell death), or
      differentiation. Such angiotensin II-mediated modulation of growth process may
      underlie various pathophysiological processes such as atherosclerosis, vascular
      and cardiac remodeling, and progression of chronic renal disease. Clearly,
      angiotensin II-induced proliferation requires complete cell progression through
      the various steps of the cell cycle. In contrast, cells undergoing angiotensin II
      mediated hypertrophy are arrested in the G1-phase. Upregulation of cell cycle
      dependent kinase inhibitors (eg, p27Kip1) plays an important role in this
      process. Although accumulating evidence suggests that apoptosis is cell cycle
      dependent, only few data are currently available concerning the interaction of
      angiotensin II with the cell cycle machinery in apoptosis. We review the various
      angiotensin II-mediated growth processes and their relationship to events
      governing cell cycle regulation.

PMID- 14967832
TI  - Aspirin, chance, and results in relation to blood pressure.

PMID- 14967833
TI  - Stress imaging in renal transplant candidates.

PMID- 14967834
TI  - Urinary potassium excretion and sodium sensitivity in blacks.
AB  - Based on racial differences in urinary potassium excretion and responses to
      diuretics, we present a model suggesting that a major cause of sodium sensitivity
      in blacks is an augmented activity of the Na-K-2Cl cotransport in the thick
      ascending limb of Henle's loop. This would result in an increased ability to
      conserve not only sodium but also water, and an upward and rightward shift in the
      operating point of tubuloglomerular feedback, which may cause an increase in the
      glomerular capillary hydraulic pressure and predilection to glomerular injury
      with and without hypertension. In this sense, the biological implication of
      sodium sensitivity in blacks and in humans in general has ramifications above and
      beyond salt-evoked increase in blood pressure.

PMID- 14967835
TI  - Smart gene therapy for the heart.

PMID- 14967836
TI  - Modulation of learning and memory in Dahl rats by dietary salt restriction.
AB  - The Dahl rat represents a robust animal model of salt-sensitive hypertension,
      with Dahl S rats being salt sensitive and Dahl R rats (the Dahl S counterparts)
      being salt resistant for the development of hypertension. Here we evaluate the
      effect of reduced dietary salt intake on learning and memory in the Dahl rat
      model. Salt restriction produced a significant impairment in social transmission
      of food preference and social recognition memory in Dahl S rats without affecting
      spatial learning. In contrast, social transmission of food preference and social
      recognition memory remained unaffected in Dahl R rats, whereas navigation
      performance was significantly improved. This effect on learning and memory was
      not generalized because sodium restriction did not influence object recognition
      memory in either Dahl S or Dahl R rats. The significant decrement in select
      cognitive functions in Dahl S rats produced by salt restriction are in sharp
      contrast to the well known positive effect of dietary salt restriction in
      alleviating high blood pressure and associated target organ complications,
      suggesting that caution must be exercised when weighing the benefits of salt
      restriction in improving cardiovascular health in salt-sensitive hypertension
      against the potential undesirable effects of reduced cognitive function.

PMID- 14967837
TI  - C-reactive protein modifies the relationship between blood pressure and
      microalbuminuria.
AB  - C-reactive protein (CRP) and microalbuminuria reflect intimately related
      components of the atherosclerotic disease process. Epidemiological studies found
      only modest associations between CRP and microalbuminuria. Blood pressure, one of
      the components of the metabolic syndrome in the general population, is the main
      determinant of microalbuminuria in diabetes and hypertension. We questioned
      whether CRP modifies the relationship of blood pressure and other cardiovascular
      risk factors with microalbuminuria in a cross-sectional study in 8592 inhabitants
      from Groningen, The Netherlands. The crude data showed an increase in the
      prevalence of microalbuminuria with increasing CRP quartiles (4.8, 9.6, 14.5, and
      18.6%, P<0.0001). On stratification for cardiovascular risk factors, the data
      revealed a significant and positive interaction between mean arterial pressure
      (MAP) and quartiles of CRP with respect to the risk of microalbuminuria (Wald
      statistic 9.2, P=0.03). In subjects with a MAP <90 mm Hg, a nonsignificant trend
      in the association between CRP quartiles and microalbuminuria was found
      (prevalence: 3.9%, 5.8%, 6.6%, 8.7%; P=0.11). This trend was much steeper and
      significant in subjects with an MAP >90 mm Hg (prevalence: 6.7%, 13.6%, 20.4%,
      25.1%; P<0.0001). Controlling for other risk factors in multivariate analyses,
      the positive interaction persisted (P=0.0004). No significant interactions
      between other risk factors and CRP with respect to the risk of microalbuminuria
      were encountered. Thus, CRP modifies the relation between blood pressure and
      microalbuminuria.

PMID- 14967838
TI  - Fas signaling induces Akt activation and upregulation of endothelial nitric oxide
      synthase expression.
AB  - A growing body of evidence has shown that Fas, a death receptor, mediates
      apoptosis-unrelated biological effects. Here, we report that Fas engagement with
      Fas ligand induced activation of Akt and upregulation of endothelial nitric oxide
      synthase expression without induction of apoptosis. In the presence of the
      phosphatidylinositol 3-kinase inhibitor wortmannin, Fas ligand, however, induced
      apoptosis instead of upregulation of endothelial nitric oxide synthase
      expression. In vivo, systolic blood pressure was slightly higher in mutant mice
      with decreased cell surface Fas expression (lpr mice) compared with wild-type
      mice. In addition, chronic inhibition of nitric oxide synthesis by N(G)-nitro-l
      arginine induced a progressive increase in the levels of blood pressure in wild
      type mice, whereas no further increase in the levels of blood pressure was
      observed in lpr mice. Furthermore, acetylcholine caused a lesser endothelium
      dependent relaxation of the strips from lpr mice compared with wild-type mice,
      although the vasoconstrictor potency of phenylephrine was not different between
      the two groups. These findings indicate that Fas signaling may have a role in the
      regulation of endothelial function and blood pressure through modulating
      endothelial nitric oxide synthase expression in the Akt signal-dependent manner.

PMID- 14967839
TI  - Elevated BSC-1 and ROMK expression in Dahl salt-sensitive rat kidneys.
AB  - This study compared the expression of enzymes and transport and channel proteins
      involved in the regulation of sodium reabsorption in the kidney of Dahl salt
      sensitive (DS) and salt-resistant Brown-Norway (BN) and consomic rats (SS.BN13),
      in which chromosome 13 from the BN rat has been introgressed into the DS genetic
      background. The expression of the Na+/K+/2Cl- (BSC-1) cotransporter, Na+/H+
      exchanger (NHE3), and Na+-K+-ATPase proteins were similar in the renal cortex of
      DS, BN, and SS.BN13 rats fed either a low-salt (0.1% NaCl) or a high-salt (8%
      NaCl) diet. The expression of the BSC-1 and the renal outer medullary K+ channel
      (ROMK) were higher, whereas the expression of the cytochrome P4504A proteins
      responsible for the formation of 20-hydroxyeicosatetraenoic (20-HETE) was lower
      in the outer medulla of the kidney of DS than in BN or SS.BN13 rats fed either a
      low-salt or a high-salt diet. In addition, the renal formation and excretion of
      20-HETE was lower in DS than in BN and SS.BN13 rats. These results suggest that
      overexpression of ROMK and BSC-1 in the thick ascending limb combined with a
      deficiency in renal formation of 20-HETE may predispose Dahl S rats fed a high
      salt diet to Na+ retention and hypertension.

PMID- 14967840
TI  - WNK4 intron 10 polymorphism is not associated with hypertension.
AB  - A polymorphism in intron 10 of the serine-threonine kinase with no lysine (K) 4
      gene WNK4 (G-->A, base 1156666 on chromosome 17) has recently been associated
      with essential hypertension in a white American population. We have attempted to
      replicate this finding in a well characterized cohort of 184 unrelated
      hypertensive Australians of British extraction in which biological power was
      enhanced by them each having 2 hypertensive parents. Controls were 219
      normotensive ethnically matched subjects whose parents were both normotensive.
      Genotyping was performed using the homogeneous MassEXTEND Assay. This showed a
      frequency of 0.10 for the minor allele in each group (P=0.88). Moreover, blood
      pressure, body mass index, sex, and plasma lipid levels were similar across
      genotypes. In conclusion, our study provides no support for an association of the
      intron 10 variant of WNK4 with essential hypertension in the Anglo-Australian
      population studied.

PMID- 14967841
TI  - Isolation and culture of arterial smooth muscle cells from human placenta.
AB  - A simple and economical technique was developed to isolate and culture human
      arterial smooth muscle cells from chorionic plate vessels. Placentas from healthy
      women were collected at the time of term delivery. Chorionic plate arteries were
      identified, excised, and cut into small pieces. An explant technique was used to
      grow cultures of placental arterial smooth muscle (PASM) cells. Small pieces of
      vessel with lumens down were placed in 100-mm culture plates and grown in
      Dulbecco modified eagle medium and 10% fetal bovine serum. Cells appeared from
      explants within 1 week and grew to confluence in approximately 4 weeks. At
      confluence, PASM cell cultures had a uniform cell morphology that was
      characterized by elongated cells in parallel rows, typical of smooth muscle
      cells. Smooth muscle cell phenotype was evaluated by morphology and by
      immunoblotting and immunofluorescence of smooth muscle myofilament proteins. All
      PASM cell cultures expressed alpha-smooth muscle actin, beta-tropomyosin, and h
      caldesmon. Expression was similar to that of human aortic smooth muscle cells,
      but not to endothelial cells or fibroblasts. PASM cells stained uniformly for
      alpha-smooth muscle actin and lacked staining for a fibroblast-specific antigen.
      PASM cells were evaluated for their response to inflammatory mediators, tumor
      necrosis factor-alpha, and interleukin-1beta by measurement of interleukin-8
      production. Cells cultured for 18 hours showed a progressive increase in
      interleukin-8 production with time. Treatment with inflammatory mediators
      increased interleukin-8 production by 3-fold as compared with media control. This
      technique provides a simple method to obtain normal human arterial smooth muscle
      cells for in vitro studies of physiology and pathophysiology.

PMID- 14967842
TI  - Focal adhesion protein zyxin is a mechanosensitive modulator of gene expression
      in vascular smooth muscle cells.
AB  - Excessive deformation of vascular smooth muscle cells (SMCs) caused by a
      prolonged increase in blood pressure (eg, in hypertension) results in an adaptive
      remodeling of the vessel wall that is characterized by SMC hypertrophy or
      hyperplasia and contributes to fixation of the increase in blood pressure. The
      onset of this process is characterized by a unique change in gene expression in
      the SMC. However, thus far, no transcription factor has been identified that
      specifically mediates mechanosensitive gene expression in these cells. Therefore,
      the role of a putative mechanotransducer, the cytoskeletal protein zyxin, was
      investigated in rat aortic cultured SMCs. Immunofluorescence and Western blot
      analysis revealed that on exposure to cyclic stretch, but not to osmotic stress
      or treatment with proinflammatory cytokines, zyxin dissociates from focal
      adhesions and accumulates in the nucleus. Unlike zyxin, vinculin, another focal
      adhesion-associated protein, did not translocate. Moreover, antisense
      oligonucleotide downregulation of zyxin protein abundance suggested that zyxin
      accumulation in the nucleus is a prerequisite for mechanosensitive gene
      expression in these cells. Thus, stretch-induced endothelin B receptor
      expression, for example, was attenuated, whereas that of tenascin-C was augmented
      after zyxin suppression. The data are consistent with a role for zyxin in
      transducing mechanical stimuli from the cell membrane to the nucleus in vascular
      SMCs and in controlling the expression of mechanosensitive genes that have been
      implicated in hypertension-induced arterial remodeling.

PMID- 14967843
TI  - Evidence for a gene on chromosome 13 influencing postural systolic blood pressure
      change and body mass index.
AB  - Previous analysis in the Hypertension Genetic Epidemiology Network (HyperGEN) of
      the National Heart Lung and Blood Institute (NHLBI) Family Blood Pressure
      Program, a multicenter study of genetic and environmental factors related to
      hypertension, indicated regions of linkage for blood pressure traits together
      with several coincident regions for phenotypically correlated traits, including
      systolic blood pressure (SBP) response to a postural challenge and body mass
      index (BMI). Motivated by these findings and by our desire to better understand
      the physiology of these traits, we conducted bivariate linkage analysis of
      postural SBP change and BMI. Sibships in HyperGEN were recruited from 5 field
      centers in Massachusetts, North Carolina, Minnesota, Utah, and Alabama. All
      available affected siblings, their parents, and selected nonmedicated offspring
      were recruited. Among 1636 whites and 1747 blacks, we performed a maximum
      likelihood bivariate genome scan for quantitative trait loci influencing postural
      SBP change and BMI, similarly adjusted for race, study center, sex, age, and age
      by-sex interactions. Genome scans were performed using SOLAR (version 2.0) and
      race-specific marker allele frequencies derived from founders. The maximum genome
      wide logarithm of odds (LOD) score of 3.2 was detected on chromosome 13 at 24 cM.
      This marker (D13S493) lies within 20 cM of a marker previously linked to BMI in
      the Family Heart Study and is substantially higher than the univariate linkage
      for each trait (LOD scores for BMI and postural SBP change were 2.4 and 0.9,
      respectively). These findings suggest that a gene(s) on chromosome 13q jointly
      regulates the SBP response to postural change and BMI.

PMID- 14967844
TI  - From inflammation to fibrosis: a stiff stretch of highway.

PMID- 14967845
TI  - Hypertensive myocardial fibrosis and diastolic dysfunction: another model of
      inflammation?
AB  - Excessive myocardial fibrosis deteriorates diastolic function in hypertensive
      hearts. Involvement of macrophages is suggested in fibrotic process in various
      diseased situations. We sought to examine the role of macrophages in myocardial
      remodeling and cardiac dysfunction in pressure-overloaded hearts. In Wistar rats
      with suprarenal aortic constriction, pressure overload induced perivascular
      macrophage accumulation and fibroblast proliferation with a peak at day 3,
      decreasing to lower levels by day 28. Myocyte chemoattractant protein (MCP)-1
      mRNA was upregulated after day 1, peaking at day 3 and returning to insignificant
      levels by day 28, whereas transforming growth factor (TGF)-beta induction was
      observed after day 3, with a peak at day 7, and remained relatively elevated at
      day 28. After day 7, concentric left ventricular (LV) hypertrophy developed,
      associated with reactive fibrosis and myocyte hypertrophy. At day 28,
      echocardiography showed normal LV fractional shortening but decreased ratio of
      early to late filling wave of transmitral Doppler velocity, and hemodynamic
      studies revealed elevated LV end-diastolic pressure, suggesting normal systolic
      but impaired diastolic function. Chronic treatment with an anti-MCP-1 monoclonal
      neutralizing antibody inhibited not only macrophage accumulation but also
      fibroblast proliferation and TGF-beta induction. Furthermore, the neutralizing
      antibody attenuated myocardial fibrosis, but not myocyte hypertrophy, and
      ameliorated diastolic dysfunction without affecting blood pressure and systolic
      function. In conclusion, roles of MCP-1-mediated macrophage accumulation are
      suggested in myocardial fibrosis in pressure-overloaded hearts through TGF-beta
      mediated process. Inhibition of inflammation may be a new strategy to prevent
      myocardial fibrosis and resultant diastolic dysfunction in hypertensive hearts.

PMID- 14967846
TI  - The cardiorenal connection.

PMID- 14967848
TI  - Universal neonatal hearing screening: to screen or not to screen.

PMID- 14967847
TI  - Combination of renin-angiotensin system polymorphisms is associated with altered
      renal sodium handling and hypertension.
AB  - Genes of the renin-angiotensin-aldosterone system (RAAS) are natural candidates
      for sodium homeostasis and blood pressure regulation. To investigate the effect
      of a combination of polymorphisms of RAAS genes on renal sodium handling and
      blood pressure, 918 participants to the Olivetti Heart Study were genotyped for
      the following polymorphisms: I/D of angiotensin converting enzyme (ACE), M235T of
      angiotensinogen (AGT), A1166C of angiotensin II type-1 receptor (AT1R), and C
      344T of aldosterone synthase (CYP11B2). The segmental renal sodium handling was
      evaluated by the fractional excretions of exogenous lithium (FE-Li), uric acid
      (FE-UA), and sodium (FE-Na). Twenty-eight carriers of triple homozygosity for M
      (AGT), A (AT1R), and C (CYP11B2) in the presence of the D allele of ACE (DD/ID)
      showed lower FE-Li (20.0%+/-5.9% versus 25.0%+/-7.5%; P=0.004; mean+/-sD), FE-UA
      (6.3%+/-2.0% versus 8.2%+/-2.7%; P=0.001), and FE-Na (0.96%+/-0.41% versus
      1.22%+/-0.61%; P=0.004) as compared with all other allelic combinations (n=890),
      independently from age and body mass, suggesting an enhanced rate of proximal
      tubular sodium reabsorption. The carriers of the MM, AA, CC, DD/ID combination
      showed a substantially higher probability of being hypertensive (OR: 3.4 [(99%
      CI: 1.1 to 10.1]), independently of age and body mass. This relatively rare
      combination of allelic variants of candidate genes of the RAAS is associated with
      a significant alteration in proximal renal sodium handling and with higher risk
      of hypertension, suggesting that a combination of polymorphic variants at
      different candidate loci may affect phenotypic expression even in the absence of
      detectable effects of each variant at any single locus.

PMID- 14967849
TI  - Feasibility of implementing a universal neonatal hearing screening programme
      using distortion product otoacoustic emission detection at a university hospital
      in Hong Kong.
AB  - OBJECTIVE: To assess the feasibility of implementing a universal neonatal hearing
      screening programme using distortion product otoacoustic emission detection at a
      major teaching hospital in Hong Kong. DESIGN: Descriptive study and
      questionnaire. SETTING. Teaching hospital, Hong Kong. METHODS: A total of 1064
      infants, together with their mothers, were successfully recruited for the study.
      The participation rate was 99.3%. A three-stage hearing screening protocol using
      distortion product otoacoustic emission detection was adopted. Each of the
      participating infants was screened on three separate occasions (day 1-4, day 5
      14, and day 21-30 after birth), irrespective of the test results. A questionnaire
      was administered to 364 randomly selected mothers to determine whether as
      consumers of the hearing screening service, mothers would find screening
      desirable. RESULTS: Results of the screening demonstrated an incidence of
      permanent bilateral hearing loss (>or=40 dB in the better ear) of 0.28%. The
      results also showed that 3.5% of the screened infants were referred for
      subsequent diagnostic audiological assessment, including those suspected with
      unilateral as well as bilateral hearing loss. Data obtained were comparable to
      other reported results obtained using multi-stage screening protocols. Taking
      both the false positive rate and the default rate into consideration, the most
      appropriate time for screening in this hospital setting appeared to be around day
      5 to 14 when infants returned to the hospital's day centre as out-patients for
      routine medical follow-up. Since this day centre service is not generally
      provided by all maternity hospitals in Hong Kong, an alternative time for
      screening would be around day 21 to 30 when infants could return as out-patients
      solely for the hearing test. The results of the questionnaire suggested that most
      mothers thought a neonatal hearing screening would be desirable (91.35%). The
      majority (81.70%) indicated a preference for screening either within a few days
      of birth at the maternity ward prior to discharge from the hospital, or between 5
      and 30 days when returning to the hospital as an out-patient. CONCLUSION: It was
      concluded that a universal neonatal hearing screening programme could be readily
      implemented in a maternity hospital setting in Hong Kong.

PMID- 14967850
TI  - The effects of acute sleep deprivation on performance of medical residents in a
      regional hospital: prospective study.
AB  - OBJECTIVE: To evaluate the effects of acute sleep deprivation on the level of
      perceived occupational stress and cognitive functioning in a group of medical
      residents. DESIGN: Prospective study. SETTING: Regional hospital, Hong Kong.
      PARTICIPANTS: Twenty-one residents who had regular in-hospital on-call duties.
      MAIN OUTCOME MEASURES: From January to April 2002, participants were asked to
      complete the Raven Advanced Progressive Matrices (sets I and II) and Occupational
      Stress Inventory-Revised tests at the beginning of an on-call day. They then
      repeated the tests towards the end of their on-call duties on their next on-call
      day, at a mean (standard deviation) interval of 8.9 (2.3) days. Occupational
      Stress Inventory-Revised test scores were transformed into T-scores to provide
      information about an individual's scores relative to the scores of participants
      in a normative sample. RESULTS: The group slept for a mean (standard deviation)
      of 2.9 (1.0) hours during 29.3 (3.8) hours of on-call duties. Before the on-call
      duties, participants' mean T-scores for the Occupational Stress Inventory-Revised
      test ranged from 50.6 to 54.5 for the Occupational Role Questionnaire, 52.0 to
      57.0 for the Personal Strain Questionnaire, and 37.3 to 52.3 for the Personal
      Resources Questionnaire. After on-call duties, apart from a slight increase in
      Role Insufficiency T-scores (50.6 [5.9] versus 52.1 [6.0]; P=0.044), there was no
      significant change in all other scales of the Occupational Stress Inventory
      Revised test. The scores of the Raven Advanced Progressive Matrices test remained
      stable after the on-call duties (11.3 [1.2] versus 11.5 [0.8], P=0.129 for set I;
      29.9 [5.5] versus 30.2 [6.3], P=0.2 for set II). CONCLUSION: Acute sleep
      deprivation among medical residents was not associated with any significant
      changes in both cognitive functioning and level of stress perceived.

PMID- 14967851
TI  - Williams-Beuren syndrome in the Hong Kong Chinese population: retrospective
      study.
AB  - OBJECTIVE: To estimate the incidence and document the clinical characteristics of
      Williams-Beuren syndrome in the Hong Kong Chinese population. DESIGN: Cytogenetic
      analysis and retrospective study. SETTING: Clinical Genetic Service, Department
      of Health, Hong Kong. PATIENTS: Forty-one Chinese patients with Williams-Beuren
      syndrome. MAIN OUTCOME MEASURES: From 1 January 1995 to 30 June 2002,
      fluorescence in situ hybridisation was used to confirm diagnoses in 41 cases of
      Williams-Beuren syndrome by detecting chromosome 7q microdeletion. Case records
      were reviewed, the incidence of the condition in the local population was
      estimated, and the main clinical characteristics were determined. RESULTS: The
      minimal incidence of Williams-Beuren syndrome in this locality was estimated to
      be approximately 1 per 23500 live births. Common dysmorphic facial features
      included periorbital fullness (83%), full lips (80%), a long philtrum (51%), a
      flat nasal bridge (41%), and abnormal teeth (37%). No patients had a stellate
      iris. The majority (82%) had at least one documented cardiac anomaly; among these
      patients, peripheral pulmonary stenosis was diagnosed in 61% and supravalvular
      aortic stenosis in 45%. Nearly all (93%) of the study group exhibited
      developmental delay. CONCLUSION: As in the West, patients with Williams-Beuren
      syndrome in the Hong Kong Chinese population display craniofacial dysmorphism,
      cardiovascular anomalies, and mental deficiency. Supravalvular aortic stenosis
      the cardiac defect most commonly associated with Williams-Beuren syndrome in
      western countries-is less common than peripheral pulmonary stenosis in this
      region. Studies involving periodic cardiovascular evaluation are needed to
      confirm if this difference is significant.

PMID- 14967852
TI  - Minimally invasive parathyroidectomy by unilateral neck dissection--experience in
      a regional hospital in Hong Kong.
AB  - OBJECTIVE: To compare the efficacy and safety of minimally invasive open
      parathyroidectomy with localised unilateral neck dissection to the conventional
      method of bilateral neck exploration and parathyroidectomy as a surgical
      treatment for primary hyperparathyroidism. PATIENTS AND METHODS: Eleven patients
      diagnosed with primary hyperparathyroidism at Queen Elizabeth Hospital from 1
      January 2002 to 31 December 2002 were treated surgically with minimally invasive
      open parathyroidectomy. Their results were compared to a retrospective series of
      15 patients treated by conventional bilateral neck exploration and
      parathyroidectomy between 1 January 2001 and 31 December 2001. Demographic data;
      cure, recurrence, and complication rates; operating time; and hospital stay were
      analysed. RESULTS: The cure rate was 100% in both groups. There was no recurrence
      in either group. Minor complication rates were 9% and 20% in the minimally
      invasive open parathyroidectomy and the control groups, respectively. Mean
      operating time was 63 minutes in the minimally invasive open parathyroidectomy
      group, and 92 minutes in the control group. The mean postoperative hospital stay
      for the minimally invasive open parathyroidectomy group was 1.36 days. Three of
      these procedures were performed as day surgery. The mean hospital stay for the
      control group was 2.93 days. The operating time and hospital stay were
      significantly shorter in the minimally invasive open parathyroidectomy group.
      CONCLUSION: Minimally invasive open parathyroidectomy is a viable alternative
      treatment method for primary hyperparathyroidism. It has comparable cure and
      recurrence rates to the conventional approach. It is safe, with a lower
      complication rate, and has the benefits of being a shorter procedure and allowing
      a shorter hospital stay. It can be performed as day surgery, further reducing
      hospital costs.

PMID- 14967853
TI  - Clinical profile and genetic basis of Brugada syndrome in the Chinese population.
AB  - OBJECTIVE: To study the clinical profile and genetic basis of Brugada syndrome in
      Chinese patients. DESIGN: Prospective observational study. SETTING: Seven
      regional public hospitals, Hong Kong. MAIN OUTCOME MEASURES: The clinical and
      follow-up data of 50 patients (47 men, 3 women; mean age, 53 years) were
      collected, and genetic data of 36 probands and eight family members of three
      genotyped probands were analysed. RESULTS: Eight patients survived sudden cardiac
      death (group A), 12 had syncope of unknown origin but no sudden death (group B),
      and 30 were asymptomatic before recognition of Brugada syndrome (group C).
      Programmed electrical stimulation induced sustained ventricular arrhythmias in
      88% (7/8), 82% (9/11), and 27% (3/11) of patients in group A, group B, and group
      C, respectively. New arrhythmic events occurred in 50% (4/8) of patients in group
      A and 17% (2/12) of patients in group B after a mean follow-up period of 30
      (standard deviation, 13) months and 25 (7) months, respectively. All group C
      patients remained asymptomatic during a mean follow-up period of 25 (standard
      deviation, 11) months. Five of 36 probands and three of eight family members who
      underwent genetic testing were found to have a mutation in their SCN5A gene.
      CONCLUSIONS: Chinese patients with Brugada syndrome who are symptomatic have a
      high likelihood of arrhythmia recurrence, whereas asymptomatic patients enjoy a
      good short-term prognosis. The prevalence of SCN5A mutation among probands is
      14%. Thus, Chinese patients with Brugada syndrome share with their western
      counterparts similar clinical and genetic heterogeneity.

PMID- 14967854
TI  - Screening for vestibular schwannoma by magnetic resonance imaging: analysis of
      1821 patients.
AB  - OBJECTIVES: To study the spectrum of diseases that can be detected by magnetic
      resonance imaging in patients suspected to have vestibular schwannoma (acoustic
      neuroma) presenting with sensorineural or mixed hearing loss, and to assess the
      extent of the problem of hearing loss in a screened population. DESIGN:
      Retrospective study. SETTING: Diagnostic radiology and imaging department of a
      regional hospital, Hong Kong. PATIENTS: A total of 1821 consecutive patients from
      September 1999 to February 2001 with sensorineural or mixed hearing loss were
      referred by otolaryngologists for magnetic resonance imaging of the internal
      auditory canal. MAIN OUTCOME MEASURES: Vestibular schwannoma; other
      cerebellopontine angle masses and other diseases that could account for the
      patients' hearing loss. RESULTS: In all, 132 (7%) patients had positive findings
      that could explain their hearing loss. Fifty-four (41%) of the 132 patients had
      vestibular schwannoma; 39 (30%) had inflammation of the middle ear and mastoids;
      17 (13%) had ischaemic foci in the brainstem; 10 (8%) had other cerebellopontine
      angle masses or tumours; four (3%) had inner ear dysplasia; seven (5%) had
      vascular loop compression; and one (1%) had chronic cryptococcal meningitis. The
      overall incidence of vestibular schwannoma detected in this screened population
      was about 3%. CONCLUSIONS: This study indicates that magnetic resonance imaging
      is an effective tool to screen for vestibular schwannoma in patients with
      sensorineural or mixed hearing loss. It can also be used to assess a considerable
      number of different pathological conditions in patients with audiovestibular
      disorders.

PMID- 14967855
TI  - Obstructive sleep apnoea syndrome and obesity in children.
AB  - OBJECTIVE: To review data on children who have both obesity and obstructive sleep
      apnoea syndrome. DATA SOURCE: Pubmed and MEDLINE (Ovid) literature search using
      the following key words: obstructive sleep apnea syndrome, obesity, and children.
      STUDY SELECTION: Literature and data on obesity-associated obstructive sleep
      apnoea syndrome in children. DATA EXTRACTION: Review of relevant information and
      data. DATA SYNTHESIS: Different definitions of obesity and obstructive sleep
      apnoea syndrome in children were used in different studies, which made it
      difficult to compare results from different studies conducted in different
      countries. Nonetheless, obstructive sleep apnoea syndrome was found to be
      moderately prevalent among obese children-namely, 13% to 36%. The severity of
      obstructive sleep apnoea syndrome was positively related to the degree of
      obesity. Blood pressure was found to be elevated in obese children with
      obstructive sleep apnoea syndrome. Weight reduction is an effective treatment.
      CONCLUSION: Children with obesity and obstructive sleep apnoea syndrome face a
      double challenge. A holistic approach to management requires a clear
      understanding of how both problems interact.

PMID- 14967856
TI  - A case of Langerhans' cell histiocytosis of the lung presenting with haemoptysis.
AB  - Langerhans' cell histiocytosis of the lung can be part of a multisystem disorder
      or an isolated disorder. Ninety percent of adult patients with Langerhans' cell
      histiocytosis of the lung are smokers. This article reports a case of Langerhans'
      cell histiocytosis presenting with haemoptysis. The diagnostic signs on chest X
      ray, high-resolution computed tomography, and histology are highlighted, followed
      by a short review of the literature.

PMID- 14967857
TI  - Dentatorubral-pallidoluysian atrophy in two Chinese families in Hong Kong.
AB  - We report on two Hong Kong Chinese families with dentatorubral-pallidoluysian
      atrophy. Two children in one family presented with progressive myoclonic epilepsy
      syndrome, and two children in the other family presented with ataxochoreo
      athetoid symptoms. Early-onset childhood dentatorubral-pallidoluysian atrophy
      involved mental retardation, whereas myoclonic epilepsy was the predominant
      complaint in later-onset childhood version of the disease. Aspiration pneumonia
      was common in the late stage of disease. Dentatorubral-pallidoluysian atrophy is
      an autosomal dominant condition attributed to CAG trinucleotide repeats in the
      dentatorubral-pallidoluysian atrophy gene. The four children in this series had
      63 to 79 CAG repeats. The expanded allele was inherited from the father in both
      families. One father had 54 CAG repeats and was asymptomatic; the other had 66
      repeats and had an unsteady gait. Because the radiological,
      electroencephalographic, and electrophysiological findings were non-specific, we
      suggest that DRPLA gene testing should be performed in any child presenting with
      a variable combination of myoclonic epilepsy, mental retardation or developmental
      regression, and ataxochoreo-athetosis.

PMID- 14967858
TI  - Two case reports of obturator nerve block for transurethral resection of bladder
      tumour.
AB  - This report describes two cases of severe adductor muscle spasm during
      transurethral resection of bladder tumours and subsequent successful management
      with the help of obturator nerve block. Obturator nerve blocks are useful during
      surgery to remove large, advanced tumours in the distal lateral wall of the
      bladder.

PMID- 14967859
TI  - Hepatotoxicity and persistent renal insufficiency after repeated supratherapeutic
      paracetamol ingestion in a Chinese boy.
AB  - Paracetamol has always been regarded as a useful and safe drug. The risk of
      toxicity with repeated supratherapeutic paracetamol is an underrecognised
      condition. We report on a 12-month-old boy who presented with hepatotoxicity,
      disseminated intravascular coagulation and persistent renal insufficiency 4 days
      after repeated ingestion of a supratherapeutic dosage of paracetamol. To the best
      of our knowledge, this is the first reported case of paediatric chronic
      paracetamol poisoning among the Chinese population. In addition, persistent renal
      insufficiency has not been a previously reported feature of chronic paracetamol
      poisoning. We propose that renal damage is the result of the synergistic effect
      of hypoperfusion and paracetamol overdose.

PMID- 14967860
TI  - What abnormality is evident on the chest X-ray after placement of the central
      venous catheter?

PMID- 14967861
TI  - Learning from other people's mistakes.

PMID- 14967862
TI  - Prevalence of epilepsy in Hong Kong.

PMID- 14967864
TI  - Severe acute respiratory syndrome and respiratory protection.

PMID- 14967865
TI  - Wrong emphasis in case report on cholestatic jaundice.

PMID- 14967866
TI  - Substrate utilization during exercise performed with and without glucose
      ingestion in female and male endurance trained athletes.
AB  - Compared to males, females oxidize proportionately more fat and less carbohydrate
      during endurance exercise performed in the fasted state. This study was designed
      to test the hypothesis that there may also be gender differences in exogenous
      carbohydrate (CHOexo) oxidation during exercise. Healthy, young males (n = 7) and
      females (n = 7) each completed 2 exercise trials (90 min cycle ergometry at 60%
      VO2peak), 1 week apart. Females were eumenorrheic and were tested in the
      midfollicular phase of their menstrual cycle. Subjects drank intermittently
      either 8% CHOexo (1 g glucose x kg x h(-1)) enriched with U-13C glucose or an
      artificially sweetened placebo during the trial. Whole-body substrate oxidation
      was determined from RER, urinary urea excretion, and the ratio of 13C:12C in
      expired gas during the final 60 min of exercise. During the placebo trial, fat
      oxidation was higher in females then in males (0.42 +/- 0.07 vs 0.32 +/- 0.09
      g.min(-1).kg LBM(-1) x 10(2)) at 30 min of exercise (p < .05). When averaged over
      the final 60 min of exercise, the relative proportions of fat, total
      carbohydrate, and protein were all similar between groups. During CHOexo
      ingestion, both the ratio of 13C:12C in expired gas (p < .05) and the proportion
      of energy derived from CHOexo relative to LBM (p < .05) were higher in females
      compared to males at 75- and 90-min exercise. When averaged over the final 60 min
      of exercise, the percentage of CHOexo to the total energy contribution tended to
      be higher in females (14.3 +/- 1.2%) than in males (11.2 +/- 1.2%; p = .05).
      Compared to males, females may oxidize a greater relative proportion of CHOexo
      during endurance exercise which, in turn, may spare more endogenous fuel. Based
      on these observations, ingested carbohydrate may be a particularly beneficial
      source of fuel during endurance exercise for females.

PMID- 14967867
TI  - Effect of variable carbohydrate intake on exercise performance in female
      endurance cyclists.
AB  - This study measured the effect of variable carbohydrate intake on time to
      exhaustion, variations in heart rate (HR), respiratory exchange ratio (RER), and
      rating of perceived exertion (RPE) in female endurance cyclists during an
      exercise trial. Subjects were 11 eumenorrheic women with maximal oxygen
      consumption (VO2max) 60.1 +/- 5.1 ml/kg who habitually cycled at least 100 miles
      per week. In a crossover design, each woman was randomly assigned to a eucaloric
      diet providing 8, 5, or 3 g of CHO/kg of body weight. Subjects cycled at least
      100 miles while adhering to the diet for 6 days. The exercise trial was performed
      on the 7th day, consisting of a 60 min cycle at 70% VO2max, followed by an
      increase in intensity to 90% VO2max until the intensity could no longer be
      maintained. Results indicated no difference in mean time to exhaustion, heart
      rate, or RPE. RER increased over time-elapsed (F = 40.4, p < .001) and across
      diets (F = 6.1, p = .015). CONCLUSIONS: Female endurance cyclists did not
      experience a difference in time to exhaustion, HR, or RPE with different levels
      of CHO intake during an endurance trial. RER varied with diet at submaximal
      intensities. Further research is needed to determine the optimal level of CHO
      intake for this population.

PMID- 14967868
TI  - Effect of pre-exercise carbohydrate ingestion on plasma cytokine, stress hormone,
      and neutrophil degranulation responses to continuous, high-intensity exercise.
AB  - The purpose of the present study was to examine the effect of pre-exercise
      carbohydrate (CHO) ingestion on circulating leukocyte numbers, plasma interleukin
      (IL)-6, plasma cortisol, and lipopolysaccharide (LPS)-stimulated neutrophil
      degranulation responses in moderately trained male cyclists who completed
      approximately 1-h of high-intensity cycling. The influence of the timing of pre
      exercise CHO ingestion was investigated in 8 subjects who consumed 75 g CHO as a
      glucose solution at either 15 (-15 trial), or 75 (-75 trial) min before the onset
      of exercise. The influence of the amount of pre-exercise CHO ingestion was
      investigated in a further 10 subjects who consumed either 25 g or 200 g CHO as a
      glucose solution or a placebo 45 min before the onset of exercise. At the onset
      of exercise in the timing experiment, the plasma glucose concentration was
      significantly (p < .05) lower on the -75 trial compared with pre-drink values,
      and the plasma cortisol concentration and neutrophil to lymphocyte (N/L) ratio
      were significantly (p < .05) elevated in the post-exercise period. In the -15
      trial, plasma glucose level was well maintained, and the plasma cortisol
      concentration and N/L ratio were not significantly elevated above resting levels.
      However, LPS-stimulated neutrophil degranulation was similar in the -15 and -75
      trials. The amount of CHO ingested had no effect on the magnitude of the rise in
      the N/L ratio compared with placebo when consumed 45 min pre-exercise. Finally,
      although an exercise-induced increase in the plasma IL-6 concentration was
      observed, this effect was independent of pre-exercise CHO ingestion.

PMID- 14967869
TI  - Influence of carbohydrate ingestion on cytokine responses following acute
      resistance exercise.
AB  - The effect of carbohydrate supplementation (CHO) on interleukin 2 (IL-2) and
      interleukin 5 (IL-5) secretion following acute resistance exercise was examined
      in 9 resistance-trained males. Subjects completed a randomized, double-blind
      protocol with exercise separated by 14 days. The exercise consisted of a high
      intensity, short rest interval squat workout. Subjects consumed 1.0 g x kg body
      mass(-1) CHO or an equal volume of placebo (PLC) 10 min prior to and 10 min
      following exercise. Blood was collected at rest (REST), immediately post exercise
      (POST), and at 1.5 h of recovery (1.5 h POST). Isolated peripheral blood
      mononuclear cells were stimulated with PHA and assayed for IL-2 and IL-5
      secretion. IL-2 secretion was significantly decreased at POST for both the PLC
      and CHO groups. However, the degree of decrease was less in the CHO group (16%)
      than in the PLC group (48%), and this difference was statistically significant.
      These responses were transient, and the values returned to normal by 1.5 h POST.
      A mild and transient but significant decrease in IL-5 secretion by the PLC group
      was observed at POST (26%) compared to REST. No significant decrease was observed
      in IL-5 secretion for CHO from REST to POST (12%). These data support a possible
      effect of carbohydrate supplementation on IL-2 and IL-5 secretion following high
      intensity resistance exercise.

PMID- 14967870
TI  - Endurance capacity and high-intensity exercise performance responses to a high
      fat diet.
AB  - The effects of adaptation to a high-fat diet on endurance performance are
      equivocal, and there is little data regarding the effects on high-intensity
      exercise performance. This study examined the effects of a high-fat/moderate
      protein diet on submaximal, maximal, and supramaximal performance. Twenty non
      highly trained men were assigned to either a high-fat/moderate protein (HFMP; 61%
      fat diet) (n = 12) or a control (C; 25% fat) group (n = 8). A maximal oxygen
      consumption test, two 30-s Wingate anaerobic tests, and a 45-min timed ride were
      performed before and after 6 weeks of diet and training. Body mass decreased
      significantly (-2.2 kg; p < or = .05) in HFMP subjects. Maximal oxygen
      consumption significantly decreased in the HFMP group (3.5 +/- 0.14 to 3.27 +/-
      0.09 L x min(-1)) but was unaffected when corrected for body mass. Perceived
      exertion was significantly higher during this test in the HFMP group. Main time
      effects indicated that peak and mean power decreased significantly during bout 1
      of the Wingate sprints in the HFMP (-10 and -20%, respectively) group but not the
      C (-8 and -16%, respectively) group. Only peak power was lower during bout 1 in
      the HFMP group when corrected for body mass. Despite significantly reduced RER
      values in the HFMP group during the 45-min cycling bout, work output was
      significantly decreased (-18%). Adaptation to a 6-week HFMP diet in non-highly
      trained men resulted in increased fat oxidation during exercise and small
      decrements in peak power output and endurance performance. These deleterious
      effects on exercise performance may be accounted for in part by a reduction in
      body mass and/or increased ratings of perceived exertion.

PMID- 14967871
TI  - Comparison of 24 hour whole body versus patch tests for estimating body surface
      electrolyte losses.
AB  - PURPOSE: To compare dermal electrolyte loss between whole body and regional patch
      methods in women during 24-h. METHODS: Dermal loss was collected in 6 healthy
      women mean age 27 +/- 4 years, while consuming 936 mg/d sodium, 1764 mg/d
      potassium, 696 mg/d calcium, and 152 mg/d magnesium. Twenty-four hour whole body
      dermal loss was collected using cotton suits by a washdown procedure. Twenty-four
      hour patch loss was collected from 8 patches placed on the legs, arms, and back.
      RESULTS: Dermal loss from whole body was 108 +/- 110 mg/d sodium, 133 +/- 87 mg/d
      potassium, 103 +/- 22 mg/d calcium, and 35 +/- 13 mg/d magnesium. Electrolyte
      content from the 8 patches was similar among sites and ranged from 1.01-1.41 mg/d
      sodium, 0.35-0.83 mg/d potassium, 1.0-1.45 mg/d calcium, and 0.43-0.49 mg/d
      magnesium. Projections from patches to whole body by the ratio of body surface
      area appear to overestimate actual whole body losses by 3.2X for sodium and
      calcium, 3.6X for magnesium, and 1.3X for potassium. CONCLUSIONS: Regional patch
      methods are more appropriate for relative comparisons than for accurately
      determining total daily dermal electrolyte losses.

PMID- 14967872
TI  - No effect of pre-exercise meal on substrate metabolism and time trial performance
      during intense endurance exercise.
AB  - To determine the effect of macronutrient composition of pre-exercise meals on
      exercise metabolism and performance, 8 trained men exercised for 30 min above
      lactate threshold (30LT), followed by a 20-km time trial (TT). Approximately 3.5
      h before exercise, subjects consumed a carbohydrate meal (C; 3 g
      carbohydrate/kg), an isoenergetic fat meal (F; 1.3 g fat/kg) or a placebo meal
      (P; no energy content) on 3 separate occasions in randomized order. Treatments
      had no effect on carbohydrate oxidation during exercise, but C decreased whole
      body fat oxidation during the last 5 min of 30LT and TT, respectively (3.2 +/-
      1.6 and 4.8 +/- 2.1 micromol/kg(-1) x min(-1), p < .05) when compared to F (13.3
      +/- 1.6 and 16.5 +/- 2.7 micromol x kg(-1) x min(-1)) and P (15.9 +/- 2.7 and
      17.0 +/- 3.2 micromol x kg(-1) x min(-1)). Glucose rate of appearance (Ra) and
      disappearance (Rd), and muscle glycogen utilization were not significantly
      different among treatments during exercise. TT performances were similar for C,
      F, and P (32.7 +/- 0.5 vs. 33.1 +/- 1.1 and 33.0 +/- 0.8 min, p > 0.5). We
      conclude that the consumption of a pre-exercise meal has minor effects on fat
      oxidation during high-intensity exercise, and no effect on carbohydrate oxidation
      or TT performance.

PMID- 14967873
TI  - Effects of creatine on body composition and strength gains after 4 weeks of
      resistance training in previously nonresistance-trained humans.
AB  - This study examined the effects of Cr supplementation on muscle strength in
      conjunction with resistance training in nonresistance-trained males utilizing
      strategies previously reported in the literature to help optimize muscle CR
      uptake. Nineteen nonresistance-trained males underwent 4 weeks of resistance
      training (3 days x week(-1)) while assigned to Cr (20 g x d(-1) Cr + 140 g x d(
      1) glucose) for 7 days (loading), followed by 5 g x d(-1) Cr + 35 g x d(-1)
      glucose for 21 days (maintenance; n = 9) or placebo (160 g x d(-1) glucose
      [loading] followed by 40 g x d(-1) [maintenance; n = 10]). In subjects classified
      as "responders" to Cr on the basis of body mass changes (n = 7), the magnitude of
      change in 180 degrees x s(-1) isokinetic (p = .029) and isometric (p = .036)
      force was greater compared to the placebo group. A positive correlation was found
      between changes in body mass and 180 degrees x s(-1) isokinetic (loading: r =
      0.68, p = .04; maintenance: r = 0.70, p = .037) and isometric (loading: r = 0.82,
      p < .01) force. Estimated Cr uptake was also positively correlated with changes
      in isometric force (r = 0.71, p = .033). These results indicate that Cr
      supplementation can increase muscle strength (allied with 4 weeks of strength
      training) but only in subjects whose estimated Cr uptake and body mass are
      significantly increased; the greater the Cr uptake and associated body mass
      changes, the greater the performance gains.

PMID- 14967874
TI  - Eating patterns and meal frequency of elite Australian athletes.
AB  - We undertook a dietary survey of 167 Australian Olympic team athletes (80 females
      and 87 males) competing in endurance sports (n = 41), team sports (n = 31),
      sprint- or skill-based sports (n = 67), and sports in which athletes are weight
      conscious (n = 28). Analysis of their 7-day food diaries provided mean energy
      intakes, nutrient intakes, and eating patterns. Higher energy intakes relative to
      body mass were reported by male athletes compared with females, and by endurance
      athletes compared with other athletes. Endurance athletes reported substantially
      higher intakes of carbohydrate (CHO) than other athletes, and were among the
      athletes most likely to consume CHO during and after training sessions. Athletes
      undertaking weight-conscious sports reported relatively low energy intakes and
      were least likely to consume CHO during a training session or in the first hour
      of recovery. On average, athletes reported eating on approximately 5 separate
      occasions each day, with a moderate relationship between the number of daily
      eating occasions and total energy intake. Snacks, defined as food or drink
      consumed between main meals, provided 23% of daily energy intake and were chosen
      from sources higher in CHO and lower in fat and protein than foods chosen at
      meals. The dietary behaviors of these elite athletes were generally consistent
      with guidelines for sports nutrition, but intakes during and after training
      sessions were often sub-optimal. Although it is of interest to study the
      periodicity of fluid and food intake by athletes, it is difficult to compare
      across studies due to a lack of standardized terminology.

PMID- 14967875
TI  - The nutritional and anthropometric status of Gaelic football players.
AB  - The aim of this study was to investigate the dietary intakes and anthropometric
      profiles of county and club Gaelic football players and compare them to soccer
      players and control subjects. Seven-day dietary records were analyzed and
      anthropometric measurements were taken midway through the Gaelic football
      competitive season. The county group with a mean height of 1.82 +/- 0.04 m were
      significantly taller (p < .05) and had less body fat that any other group. The
      county and club teams consumed 151 +/- 11 and 150 +/- 16 kJ x kg(-1) x day(-1),
      respectively, with 52.2 +/- 5% and 49.5 +/- 9% of their energy intakes as
      carbohydrate. This compares to 173 +/- 11 kJ x kg(-1) x day(-1) for the soccer
      players and 159 +/- 8 kJ x kg(-1) x day(-1) for the controls, with 57 +/- 4% and
      44.9 +/- 5% of their energy from carbohydrate. The nature of Gaelic football
      demands a balanced diet, rich in energy and carbohydrate and with adequate
      calcium is consumed; the subjects needed to increase these dietary components in
      order to meet the energetic demands of competition and training. Additional
      nutritional counseling was provided on an individual basis.

PMID- 14967876
TI  - The IOC consensus on sports nutrition 2003: new guidelines for nutrition for
      athletes.

PMID- 14967877
TI  - Nutrition as a determinant of blood rheology and fibrinogen in athletes.
AB  - Blood rheology is influenced by metabolism and nutrition. We investigated this
      issue in 41 elite athletes exercising 13+/-0.9 hr/wk (mean age: 23.9+/-0.67 yr;
      mean VO2max: 52.6+/-2.3 ml/min/kg body weight) with a standardised nutritional
      questionnaire suitable for sports medicine. Calorie intake (% of recommended
      intake) was negatively correlated with the RBC disaggregability threshold (r=
      0.505, p=0.01). There were negative correlations between fibrinogen and protein
      intake (% of the total caloric intake r=-0.787, p=0.0008; amount in g/kg/day r=
      0.597, p=0.03). Accordingly, the RBC disaggregability threshold was also
      correlated negatively with protein intake (r=-0.508, p=0.05). Lipid intake
      (g/kg/day) was negatively correlated with the RBC disaggregability threshold (r=
      0.564, p=0.03) and positively to the hematocrit/viscosity ratio (r=0.531,
      p=0.03). Carbohydrate intake (g/kg/day) was positively correlated with whole
      blood viscosity (r=0.517, p=0.04) and negatively to the hematocrit/viscosity
      ratio (r=-0.4863, p=0.05). In addition fibrinogen was negatively correlated with
      hematocrit (r=-0.4129, p=0.036) and positively with a host of aggregation
      parameters (p<0.001). Therefore fibrinogen levels and red cell rheology exhibit
      correlations with the nutritional status in athletes. Low protein intake appears
      to be associated with (mildly) raised fibrinogen and aggregability, and low
      calorie intake is associated with lower RBC disaggregability.

PMID- 14967878
TI  - Haemorheological variables as a rheumatoid arthritis activity indicator.
AB  - OBJECTIVE: To investigate if blood hyperviscosity in RA patients is due to a
      reduced erythrocyte deformability and, therefore, turning it into a reliable
      activity indicator, as well as a therapy follow-up marker for this pathology.
      METHODS: (1) The haemorheological profile consisting of erythrocyte
      deformability, blood and plasma viscosity, and erythrocyte membrane fluidity was
      determined in 24 AR patients and 17 healthy controls. (2) A 4 year follow-up was
      carried on in 16 patients monitoring blood viscosity, erythrocyte deformability
      and biochemical variables in relation to clinical assessment of disease activity
      (Disease Activity Score "DAS 28-4"). RESULTS: Erythrocyte deformability and
      membrane fluidity were impaired in RA patients compared to controls (p<0.001).
      Blood viscosity was significantly increased and correlated with the cell rigidity
      index (r=0.85, p<0.0000) in RA patients. The follow-up showed a good correlation
      between haemorheological parameters and DAS 28-4 during disease evolution.
      CONCLUSION: our results support the hypothesis that in RA, blood hyperviscosity
      is determined by deformability loss, which in turn is due to a membrane
      rigidization. This could evidenced that a widespread cell membrane damage is
      expressed through an impaired erythrocyte deformability, turning haemorheological
      parameters into reliable tools to study disease evolution. The follow-up study
      enabled us to confirm that erythrocyte deformability is an efficient indicator of
      rheumatoid arthritis activity.

PMID- 14967879
TI  - Association between capillaroscopy, haemorheological variables and plasma
      proteins in patients bearing Raynaud's phenomenon.
AB  - Raynaud's phenomenon is a paroxysmal and reversible vasospasm affecting generally
      the acral circulatory regions. The relevance of the haemorheological alterations
      in these patients, as a source of ischemic events has been neglected. The
      objective of the present work was to evaluate and correlate the rheological blood
      properties, some biochemical parameters, e.g., plasma fibrinogen and
      immunoglobulin levels, and periungual capillaroscopy. The explicative variables
      considered were: blood viscosity, plasma viscosity, erythrocyte rigidity index,
      plasma fibrinogen, erythrocyte sedimentation rate, erythrocyte aggregate size,
      erythrocyte aggregation rate and serum immunoglobulin (IgG and IgM). The response
      variable was the nailfold capillary pattern categorised as either normal or
      pathological. Fibrinogen, erythrocyte aggregation rate and IgM are significantly
      higher in patients with a pathological pattern in comparison with patients
      bearing a normal one. The statistical analysis enabled us the modelling of the
      pathological pattern occurrence probability in function of plasma fibrinogen.
      Consequently, 100 mg/dl plasma fibrinogen increase, increases twice the
      probability of presenting a pathological pattern. Therefore, we can conclude that
      high levels of fibrinogen in Raynaud's phenomenon patients are associated with
      impaired skin microcirculation assessed by periungual capillaroscopy.

PMID- 14967880
TI  - The influence of cryoglobulins on the temperature-dependent erythrocyte
      aggregation in vitro by backscattering nephelometry.
AB  - Nephelometry technique was used to register the alterations of the scattering
      signal from a whole blood sample due to erythrocyte aggregates in stasis and
      under controlled shear stress. The measured parameters were: the characteristic
      times of linear and three-dimensional aggregates formation, and the strength of
      aggregates of different types. These parameters depend on the sample temperature
      in the range of 2/50 degrees C. Temporal parameters of the aggregation process
      strongly increase (by 3 times) at temperature 45 degrees C. For samples of normal
      blood the aggregates strength parameters do not significantly depend on the
      sample temperature, whereas for blood samples from patients with cryoglobulinemia
      high increase of the strength of both three-dimensional and linear aggregates and
      decrease of time of linear aggregates formation at low temperature of the sample
      (4 degrees C) was observed. The difference of these parameters of the
      pathological blood from that of the normal at room temperature was quite
      opposite. Possible reasons of such behavior of aggregation state of blood and
      explanation of the observed effects are suggested.

PMID- 14967881
TI  - Effects of localized cutaneous vascular alteration on reactive hyperemia.
AB  - BACKGROUND: Cutaneous microcirculation shows a distinctive spatiotemporal
      inhomogeneity. Therefore provocation tests are necessary to receive significant
      and reproducible data. The present study investigated the effect of localized
      cutaneous vascular alteration, like in psoriasis vulgaris, on different
      parameters of reactive hyperemia (peak capillary blood cell velocity [pCBV],
      postocclusive reactive hyperemia [PRH%], and time to peak capillary blood cell
      velocity [tpCBV]). MATERIAL AND METHODS: Psoriatic plaques and normal skin on the
      contralateral side of 20 patients with psoriasis vulgaris were examined by Laser
      Doppler Anemometry. Capillary blood cell velocity was measured before
      suprasystolic occlusion and during postocclusive hyperemia. RESULTS: Compared to
      normal skin psoriatic plaques showed a significant increase of peak capillary
      blood cell velocity (pCBV, normal skin: 0.89+/-0.23 mm/s, psoriatic plaque:
      2.03+/-0.94 mm/s), resting capillary blood cell velocity (rCBV, normal skin:
      0.43+/-0.12 mm/s psoriatic plaque: 0.72+/-0.20 mm/s) and postocclusive reactive
      hyperemia (PRH%, normal skin: 107%, psoriatic plaque: 180%). The time to peak
      capillary blood cell velocity (tpCBV) during reactive hyperemia did not change
      significantly. CONCLUSION: In reactive hyperemia, changing of pCBV and PRH%
      combined with unaltered tCBV indicate a dysfunction of cutaneous
      microcirculation. In contrast acute closure of upper and lower arterial extremity
      show a changed tCBV with stable pCBV and PRH%.

PMID- 14967882
TI  - Formation and relaxation of erythrocyte membrane tethers in micropipettes.
AB  - The red blood cell (RBC) membrane forms tethers in response to shear forces
      acting on tiny membrane points. Tether formation depends on viscous and elastic
      membrane properties and has been used as indicator of membrane fragility. A
      micropipette technique was used to study time dependent tether formation and
      tether relaxation of individual RBC. Point attached RBC were aspirated at a
      negative pressure of -5 mm H2O into a micropipette with an internal diameter of
      7.8 microm. If tether formation occurred and the tether reached a length of
      approximately 16 microm, the pipette was carefully pulled back. The RBC left the
      orifice of the micropipette and the tether relaxed and pulled the main body of
      the RBC back to the attachment point. The relaxation of the tethers was
      exponential. The time constant for tether relaxation was 0.144 s which is similar
      to the time constant for recovery of entire RBC from extensional elastic
      deformation. Repeated tether formation and relaxation of the same RBC led to an
      earlier begin of tether formation and changed the behavior of tether growth,
      although the relaxation time did not change. We conclude that repeated tether
      formation decreases the resistance of the RBC membrane to form tethers upon given
      shear forces. Weakening of the membrane due to repeated plastic deformation may
      play a role in the membrane loss of circulating RBC during aging.

PMID- 14967883
TI  - Hemorheology, melatonin and pinealectomy. What's the relationship? An
      experimental study.
AB  - The circadian rhythm of stroke and myocardial infarction (MI) may be related to
      the circadian rhythm of melatonin, and erythrocyte deformability may be the key
      mechanism in this relationship. Therefore, this study has been performed to
      determine if there is a relationship between the pineal gland and melatonin and
      red cell deformability. Twenty-eight rats underwent pinealectomy, pinealectomy
      plus melatonin administration (200 mg/kg), or no treatment (n=7 in each group).
      Erythrocyte deformability was determined using the filtration technique. The
      results are reported in mean (+/-SD) seconds: control: 1.45+/-0.44; pinealectomy
      (A): 1.55+/-0.16; pinealectomy (B): 1.34+/-0.26 and pinealectomy and melatonin:
      2.56+/-0.69. Pinealectomy by itself did not cause any statistically significant
      change in erythrocyte deformability but the addition of melatonin significantly
      decreased it. These results suggest a relationship between melatonin and
      erythrocyte deformability. Further investigations may uncover the causes of the
      circadian rhythm of stroke and MI, which may help improve chronobiological
      therapies.

PMID- 14967884
TI  - Polymorphonuclear leukocyte integrin profile in vascular atherosclerotic disease.
AB  - Leukocyte-endothelial interactions could have a pathogenic role in atherogenesis.
      Adhesion molecules expressed by endothelial cells, such as intercellular adhesion
      molecule 1 (ICAM-1), interact with leukocyte integrins mediating the firm
      adhesion of leukocytes to endothelium which is followed by their transendothelial
      migration. The aim of our research was to evaluate polymorphonuclear leukocyte
      (PMN) integrin expression, at baseline and after activation, in a group of
      subjects with chronic vascular atherosclerotic disease (VAD). In 27 subjects with
      VAD we examined, at baseline and after in vitro activation with 4-phorbol 12
      myristate 13-acetate (PMA), the PMN integrin pattern (CD11a, CD11b, CD11c, CD18)
      using indirect immunofluorescence and a flow cytometer. At baseline VAD subjects
      showed an increase of CD11a and CD18 and a decrease of Cd11b and Cd11c as
      compared to normal subjects. After activation, in normal subjects, we found an
      increase in the expression of all integrins, while in VAD subjects we observed an
      increase of CD11b and Cd11c and a decrease of Cd11a and CD18. In VAD subjects, at
      baseline, the upregulation of Cd11a and CD18 may reflect PMN in vivo activation;
      after in vitro activation, the decrease of CD11a may be related to the lack of
      cytoplasmic deposits of this molecule, while CD18 might be internalized. The
      integrin behaviour pattern in chronic VAD deserves further investigation,
      considering that integrins are potential targets of therapeutical strategies,
      with the aim of preventing the atherosclerotic plaque progression and acute
      ischaemic events.

PMID- 14967885
TI  - Effects of erythrocytapheresis transfusion on the viscoelasticity of sickle cell
      blood.
AB  - Red blood cells containing hemoglobin S are less deformable than normal
      erythrocytes and have a major effect on the viscoelasticity of blood. This
      alteration in rheology increases the impedance to flow, leading to an increase in
      RBC aggregation and reduction in oxygen saturation, which induces further
      sickling and occlusions in the microcirculation. Patients with sickle cell
      disease (SCD) can experience severe complications, such as acute pain and stroke.
      Automated red blood cell exchange transfusion, or erythrocytapheresis, is used in
      homozygous SCD (Hb SS) to replace sickled cells with normal cells, thereby
      decreasing the percentage of sickle hemoglobin (%Hb S) and maintaining a net
      balance in iron accumulation. These patients received monthly erythrocytapheresis
      with a goal to maintain a pre-pheresis %Hb S at less than 30%. In this study,
      viscoelastic parameters were used to quantify the effectiveness of this therapy
      for six patients undergoing chronic erythrocytapheresis. Whole blood viscosity,
      elasticity and relaxation time at oscillatory strains of 0.2, 1 and 5, and
      hematocrit and %Hb S were measured prior to erythrocytapheresis and 15 minutes
      after completion and compared with normal reference values at the patient's
      hematocrit. This study confirms the beneficial effects on viscosity, elasticity,
      and relaxation time of erythrocytapheresis.

PMID- 14967886
TI  - Growth-related changes in the mechanical properties of collagen fascicles from
      rabbit patellar tendons.
AB  - Growth-related changes in the mechanical properties of collagen fascicles
      (approximately 300 microm in diameter) were studied using patellar tendons
      obtained from skeletally immature 1 and 2 months old and matured 6 months old
      rabbits. Tensile properties were determined using a specially designed micro
      tensile tester. In each age group, there were no significant differences in the
      properties among cross-sectional locations in the tendon. Tangent modulus and
      tensile strength significantly increased with age; the rates of their increases
      between 1 and 2 months were higher than those between 2 and 6 months. The tangent
      modulus and tensile strength were positively correlated with the body weight of
      animals. However, growth-related changes in the mechanical properties were
      different between collagen fascicles and bulk patellar tendons, which may be
      attributable to such non-collagenous components as ground substances and also to
      mechanical interactions between collagen fascicles.

PMID- 14967887
TI  - Conductometric study of shear-dependent processes in red cell suspensions. I.
      Effect of red blood cell aggregate morphology on blood conductance.
AB  - The conductance and capacitance of flowing and quiescent red blood cell (RBC)
      suspensions were measured at a frequency of 0.2 MHz. The results demonstrate that
      the time-dependent changes in the conductance recorded during the aggregation
      process differ in nature for suspensions of short linear rouleaux, branched
      aggregates and RBC networks. It is shown that the conductance of RBC suspensions
      measured during the aggregation and disaggregation processes follows the
      morphological transformations of the RBC aggregates. Thus, this method enables
      characterization of the morphology of RBC aggregates formed in whole blood and in
      suspensions with physiological hematocrits both under flow conditions and in
      stasis. These results in combination with previous ones suggest that this
      technique can be used for studies of dynamic RBC aggregation and probably for
      diagnostic use.

PMID- 14967888
TI  - Conductometric study of shear-dependent processes in red cell suspensions. II.
      Transient cross-stream hematocrit distribution.
AB  - A novel experimental approach based on electrical properties of red blood cell
      (RBC) suspensions was applied to study the effects of the size and morphology of
      RBC aggregates on the transient cross-stream hematocrit distribution in
      suspensions flowing through a square cross-section flow channel. The information
      about the effective size of RBC aggregates and their morphology is extracted from
      the capacitance (C) and conductance (G) recorded during RBC aggregation, whereas
      a slower process of particle migration is manifested by delayed long-term changes
      in the conductance. Migration-induced changes in the conductance measured at low
      shear rates (< or =3.1 s(-1)) for suspensions of RBCs in a strongly aggregating
      medium reveal an increase to a maximum followed by a decrease to the stationary
      level. The ascending branch of G(t) curves reflects the aggregate migration in
      the direction of decreasing shear rate. A further RBC aggregation in the region
      of lower shear stresses leads to the formation of RBC networks and results in the
      transformation of the rheological behavior of suspensions from the thinning to
      the thickening. It is suggested that the descending branches of the G(t) curves
      recorded at low shear rates reflect an adjustment of the Hct distribution to a
      new state caused by a partial dispersion of RBC networks. For suspensions of non
      aggregating RBCs it is found that depending on whether the shear rate is higher
      or lower compared with the prior value, individual RBCs migrate either toward the
      centerline of the flow or in the opposite direction.

PMID- 14967889
TI  - Velocity pulse advances pressure pulse by close to 45 degrees in the rat pial
      arterioles.
AB  - In order to clarify the phase relationship between velocity pulse and pressure
      pulse propagating along microvessels, the red cell velocity and intravascular
      pressure were simultaneously measured in the rat pial arterioles of 41-53 microm
      in diameter with a high temporal resolution by a laser-Doppler anemometer and a
      servo-null micropressure system. It was found that the velocity pulse preceded
      the pressure pulse in all the measured arterioles by 18.7-35.6 ms. The
      corresponding phase difference was 43.6+/-6.9 degrees (mean +/- SD), which is not
      statistically different from 45 degrees. The value is consistent with the phase
      difference predicted for the blood flow in microvessels with a small reflection
      coefficient at frequencies as low as the heart rate of the rats. The present
      results suggest that the upstream changes in blood flow are transmitted by the
      velocity pulse faster than by the pressure pulse in the microvasculature.

PMID- 14967890
TI  - Blood soluble drag-reducing polymers prevent lethality from hemorrhagic shock in
      acute animal experiments.
AB  - Over the past several decades, blood-soluble drag reducing polymers (DRPs) have
      been shown to significantly enhance hemodynamics in various animal models when
      added to blood at nanomolar concentrations. In the present study, the effects of
      the DRPs on blood circulation were tested in anesthetized rats exposed to acute
      hemorrhagic shock. The animals were acutely resuscitated either with a 2.5%
      dextran solution (Control) or using the same solution containing 0.0005% or 5
      parts per million (ppm) concentration of one of two blood soluble DRPs: high
      molecular weight (MW=3500 kDa) polyethylene glycol (PEG-3500) or a DRP extracted
      from Aloe vera (AVP). An additional group of animals was resuscitated with
      0.0075% (75 ppm) polyethylene glycol of molecular weight of 200 kDa (PEG-200),
      which possesses no drag-reducing ability. All of the animals were observed for
      two hours following the initiation of fluid resuscitation or until they expired.
      We found that infusion of the DRP solutions significantly improved tissue
      perfusion, tissue oxygenation, and two-hour survival rate, the latter from 19%
      (Control) and 14% (PEG-200) to 100% (AVP) and 100% (PEG-3500). Furthermore, the
      Control and PEG-200 animals that survived required three times more fluid to
      maintain their blood pressure than the AVP and PEG-3500 animals. Several
      hypotheses regarding the mechanisms underlying these observed beneficial
      hemodynamic effects of DRPs are discussed. Our findings suggest that the drag
      reducing polymers warrant further investigation as a potential clinical treatment
      for hemorrhagic shock and possibly other microcirculatory disorders.

PMID- 14967891
TI  - Time-lapse videomicrographic analyses of contractions in mouse blastocysts.
AB  - Contraction has been observed in cultured blastocysts of many mammals, but little
      is known about the features of the contraction and its physiological role in
      blastocysts. The author analyzed contractions of a large number of cultured mouse
      blastocysts by time-lapse videomicrography. The results revealed that blastocysts
      repeated contractions of different degrees during the expanded stage from 10 h
      after blastocoel formation, and that the number of contractions was greater
      during the hatching period than in the periods pre- and post-hatching. The
      results also showed that the time needed for both contraction and re-expansion to
      the size before contraction tended to lengthen in blastocysts severely
      contracted. It was inferred that contractions of blastocysts occur
      physiologically in relation to myosin light chain kinase, but not due to an
      increase in permeability between trophectoderm cells in association with their
      division, or the influence of culture. Furthermore, it was inferred that re
      expansion of contracted blastocysts occurs due to active transport and
      accumulation of Na(+) from the trophectoderm cells into blastocoelic fluid as a
      result of the action of Na(+)/K(+)-ATPase activated in the membrane of
      trophectoderm cells. Our results suggested that contractions are also present in
      blastocysts developed in vivo, and that weak contractions (less than 20% volume
      reduction) play an important role in hatching, whereas strong contractions (20%
      or more volume reduction) have the effect of inhibiting hatching. From our
      results on contractions of various blastocysts, it seems possible to evaluate the
      developmental ability of embryos, i.e. embryo quality, based on contractions of
      blastocysts.

PMID- 14967892
TI  - Progesterone receptor mRNA levels during pregnancy, labor, lactation and the
      estrous cycle in rat uterus.
AB  - Progesterone plays important roles in the regulation of female reproduction. In
      this study, progesterone receptor (PR) mRNA levels in rat uterus during
      pregnancy, labor, lactation and the estrous cycle were examined by competitive RT
      PCR. During pregnancy and lactation, PR mRNA levels had decreased on day 20 of
      pregnancy (P20) and P21 compared with P15 but increased during labor. After a
      decline on day 1 of lactation (L1), PR mRNA levels had increased again on L3 and
      L14 compared with P15, P18, P20, P21 and P21pm (at 2200-2300 h on P21). There was
      no significant change in the PR mRNA level during the estrous cycle. The PR mRNA
      level did not change during 1 week of progesterone treatment or afterwards.
      Injection of 17beta-estradiol did not affect PR mRNA levels in rats treated with
      progesterone or those without any injections. In rats on P18, 17beta-estradiol
      injection did not change PR mRNA levels after sham-operation but induced an
      increase in PR mRNA levels of rats ovariectomized 6 h before the treatment. These
      results suggest that uterine PR mRNA levels are differently regulated during late
      pregnancy, labor and lactation, and during labor estrogen is one of the essential
      factors for the increase in PR mRNA levels.

PMID- 14967893
TI  - Biological activity of recombinant bovine interferon tau using an Autographa
      californica nuclear polyhedrosis virus expression system.
AB  - Bovine interferon (bIFN) tau, which plays a key role in maternal-fetal
      recognition of pregnancy, was expressed by an Autographa californica nuclear
      polyhedrosis virus expression system. cDNA coding bIFNtau was derived from
      cultured trophoblast cells. The recombinant (r) bIFNtau had high antiviral
      activity (1 x 10 (8) IU/mg) and the molecular weight of rbIFNtau was estimated to
      be 23 kDa by Western blotting analysis. We investigated the biological effect of
      rbIFNtau on prostaglandin (PG) F(2alpha) synthesis in cultured bovine endometrial
      epithelial cells in the presence or absence of oxytocin (OT, 100 nM). rbIFNtau
      suppressed basal and OT-induced PGF(2alpha) production in a dose-dependent manner
      (1-1,000 ng/ml). These results showed that biologically active rbIFNtau was
      produced in the baculovirus expression system, and that rbIFNtau had the ability
      to suppress the synthesis of PGF(2alpha) from bovine endometrial epithelial
      cells.

PMID- 14967894
TI  - Tumor necrosis factor-alpha (TNF alpha) inhibits progesterone and estradiol
      17beta production from cultured granulosa cells: presence of TNFalpha receptors
      in bovine granulosa and theca cells.
AB  - The aim of this study was to investigate whether functional tumor necrosis factor
      alpha (TNFalpha) receptors are present in the granulosa cells and the cells of
      theca interna (theca cells), obtained from bovine follicles classified into one
      of three groups. Each group was defined as either small vesicular ovarian
      follicles (small follicles; 3-5 mm in diameter), preovulatory mature ovarian
      follicles (preovulatory follicles) or atretic follicles (12-18 mm) according to
      gross examination of the corpus luteum in the epsilateral or contralateral ovary
      and the uterus (size, color, consistency and mucus), and the ratio of
      progesterone (P(4)) and estradiol-17beta (E(2)) concentrations in follicular
      fluid. A Scatchard analysis showed the presence of a high-affinity binding site
      on both granulosa and theca cells from all follicles examined (dissociation
      constant: 4.7 +/- 0.15 to 6.9 +/- 1.40 nM). Moreover, TNFalpha receptor
      concentrations in granulosa and theca cells obtained from atretic follicles were
      significantly higher than those in the cells from preovulatory follicles
      (P<0.05). Exposure of cultured granulosa cells from small antral follicles to
      recombinant human TNFalpha (rhTNFalpha; 0.06-6 nM) inhibited E(2) secretion in a
      dose-dependent fashion (P<0.01), but did not affect P(4) secretion. In addition,
      rhTNFalpha inhibited follicle stimulating hormone-, forskolin- or dibutylyl
      cyclic AMP-induced P(4) and E(2) secretion by the cells (P<0.01). These results
      indicate the presence of functional TNFalpha receptors in bovine granulosa and
      theca cells in small, preovulatory and atretic follicles, and suggest that
      TNFalpha plays a role in regulating their secretory function.

PMID- 14967895
TI  - Changes in the activities of hydroxysteroid dehydrogenases in mouse oocytes
      during meiotic maturation.
AB  - The activities of hydroxysteroid dehydrogenases (HSDs) were histochemically
      demonstrated in mouse oocytes in the process of maturation in vivo and in vitro,
      and the changes in steroid metabolism during meiotic maturation and also the
      relationship between nuclear maturation and changes in steroid metabolism in the
      cytoplasm were examined. In mouse oocytes 0 h after human chorionic gonadotrophin
      (hCG) injection, the activities of Delta(5)-3beta-HSD (with DHA, pregnenolone and
      17alpha-hydroxypregnenolone as the substrates), 17beta-HSD (estradiol-17beta and
      testosterone) and 20beta-HSD (17alpha-hydroxyprogesterone and 20beta
      hydroxyprogesterone) were observed in 87 to 97% of those, but that of 20alpha-HSD
      (20alpha-hydroxyprogesterone) was not. The percentages of oocytes showing the
      activities of Delta(5)-3beta-HSD, 17beta-HSD and 20beta-HSD did not change during
      maturation in vivo or in vitro. Oocytes with 20alpha-HSD activity appeared 4 h
      after the hCG injection or after culture for 4 h and the rates of those reached
      92 and 100%, respectively, 14 h after the hCG injection or after culture for 14
      h. In oocytes cultured for 8 h with olomoucine or 3-isobutyl-1-methylxanthine,
      nuclei were almost all in the germinal vesicle stage, and activity of 20alpha-HSD
      was observed in 84 and 89% of the treated oocytes, respectively. On the other
      hand, 81% of control oocytes showed 20alpha-HSD activity, with no significant
      difference from the rate for the olomoucine- or 3-isobutyl-1-methylxanthine
      treated oocytes. The present findings suggested that the metabolic abilities of
      progesterone, 17alpha-hydroxyprogesterone, 17alpha,20beta-dihydroxyprogesterone,
      20beta-hydroxyprogesterone, androgen and estradiol-17beta in the cytoplasm are
      constantly present in mouse oocytes in the process of maturation in vivo and in
      vitro. The results also suggested that the metabolic ability of 20alpha
      hydroxyprogesterone in mouse oocytes increases during maturation, but the change
      in the metabolic ability of such a steroid is not related to nuclear maturation.

PMID- 14967896
TI  - Abnormal structural luteolysis in ovaries of the senescence accelerated mouse
      (SAM): expression of Fas ligand/Fas-mediated apoptosis signaling molecules in
      luteal cells.
AB  - Senescence accelerated mouse-prone (SAMP) mice with a shortened life span show
      accelerated changes in many of the signs of aging and a shorter reproductive life
      span than SAM-resistant (SAMR) controls. We previously showed that functional
      regression (progesterone dissimilation) occurs in abnormally accumulated luteal
      bodies (aaLBs) of SAMP mice, but structural regression of luteal cells in aaLB is
      inhibited. A deficiency of luteal cell apoptosis causes the abnormal accumulation
      of LBs in SAMP ovaries. In the present study, to show the abnormality of Fas
      ligand (FasL)/Fas-mediated apoptosis signal transducing factors in the aaLBs of
      the SAMP ovaries, we assessed the changes in the expression of FasL, Fas, caspase
      8 and caspase-3 mRNAs by reverse transcription-polymerase chain reaction, and in
      the expression and localization of FasL, Fas and activated caspase-3 proteins by
      Western blotting and immunohistochemistry, respectively, during the estrus
      cycle/luteolysis. These mRNAs and proteins were expressed in normal LBs of both
      SAMP and SAMR ovaries, but not at all or only in trace amounts in aaLBs of SAMP,
      indicating that structural regression is inhibited by blockage of the expression
      of these transducing factors in luteal cells of aaLBs in SAMP mice.

PMID- 14967897
TI  - Prolactin gene expression in the mouse nipple.
AB  - In this study, we attempted to examine the presence of prolactin (PRL) messenger
      ribonucleic acid (mRNA) and protein in the mouse nipple and mammary gland in
      pregnancy and lactation. PRL-like substances were found by immunohistochemistry
      using an antibody against the mouse PRL (mPRL) in the sebaceous gland cells of
      the nipple during late pregnancy and lactation, and the cistern of alveoli in
      mammary glands during lactation. Western blot analysis of proteins extracted from
      the nipple and the mammary gland showed immunoreactive bands corresponding to
      molecular weights of approximate 16 kDa and 32 kDa, respectively. The expression
      of mRNA for mPRL in the nipple and mammary gland during late pregnancy and
      lactation was demonstrated by reverse transcription-polymerase chain reaction (RT
      PCR), Southern blotting, and nucleotide sequence analyses. These results suggest
      that mPRL mRNA and its translation product are synthesized in the mouse nipple.

PMID- 14967898
TI  - Use of DNA array to screen blastocyst genes potentially involved in the process
      of murine implantation.
AB  - Conceptus implantation to the mother's uterus is a complex series of events
      involving coordinated expression of numerous genes at both the embryonic and the
      uterine sides. Since there are no suitable in vivo or in vitro experimental
      models, sequential changes occurring during the peri-implantation periods have
      not been well characterized. Using GeneChip technology and a recently introduced
      murine in vitro model of implantation, the expression of embryonic genes was
      examined before and after attachment to the uterine stromal cells. Instead of RNA
      or mRNA, amplified cRNA was subjected to the GeneChip analysis because amounts of
      mRNA in each blastocyst were minimal. Among 6,500 gene transcripts examined,
      changes in mRNA levels for 802 genes were identified. Of these detections,
      transcripts previously unsuspected were changes in a group of tumor suppressor
      and stress-induced genes, whose transcripts increased as embryos attached to the
      membrane. Validity of the data was evaluated using reverse transcription
      polymerase chain reaction and in situ hybridization analyses, both of which
      confirmed developmental changes in selected gene expressions during pre- and post
      attachment periods. The present data suggest that GeneChip technology would be
      very useful for finding genes previously unsuspected, and this method should be
      used as an initial step, particularly as a screening tool, toward the dissection
      of complex mechanisms such as the processes of implantation.

PMID- 14967899
TI  - Risk factors for postpartum endometritis and the effect of endometritis on
      reproductive performance in dairy cows in Korea.
AB  - The objectives of this study were to determine the risk factors for postpartum
      endometritis by evaluating several reproductive factors in individual cows, and
      to determine the effect of endometritis on the subsequent reproductive
      performance in dairy herds in Korea. The data, including health status, parity
      and body condition score (BCS) of cows, and calving date, were collected from 320
      cows in eight dairy herds calving from January 2001 to October 2002. We used
      logistic regression to evaluate the effects of these factors on endometritis. A
      stepwise procedure, used to obtain the appropriate model with alpha=0.05,
      revealed that retained placenta, metabolic disorders and parity are the important
      risk factors for endometritis. The mean intervals from calving to first service
      and conception were prolonged (P<0.01) by 23 and 36 days, respectively, in the
      endometritis group compared to the non-endometritis group. The first service
      conception rate was lower (P<0.05) in the endometritis group (47.6%) than in the
      non-endometritis group (62.6%). The number of services per conception was higher
      (P<0.05) in the endometritis group (1.9) than in the non-endometritis group
      (1.6). We conclude that retained placenta, metabolic disorders and cow parity are
      strongly correlated with the development of postpartum endometritis, which
      decreases reproductive performance in dairy herds in Korea.

PMID- 14967900
TI  - Stage-specific effect of growth hormone on developmental competence of bovine
      embryos produced in-vitro.
AB  - Many efforts have been made to develop effective culture conditions for the
      production of bovine blastocysts. Growth hormone (GH) and glucose are known to
      affect in vitro embryo development. To improve in vitro culture conditions, the
      culture medium containing fetal calf serum (FCS) or bovine serum albumin (BSA)
      was supplemented with GH at various periods of development, and the effects of GH
      on the rate of development and the quality of the blastocysts were studied. Then,
      starting at the morula stage, the effect of glucose and GH on the rate of
      development was studied. In all experimental periods, FCS was more effective than
      BSA at improving the development rate and increasing the cell number of
      blastocysts. Adding GH to the culture medium between 18 and 48 h after
      fertilization (1-8 cell stage embryo) did not affect either the rate of
      blastulation or the cell number regardless of the serum protein (FCS or BSA).
      From 48 to 120 h after fertilization (5-cell to morula stage) GH increased the
      cell number of the blastocysts in the presence of BSA, but not in the presence of
      FCS. From 120 to 192 h after fertilization (morula to blastocyst stage), GH
      improved the developmental rate and cell number in the presence of FCS, although
      there was no significant difference when BSA was used instead of FCS as the serum
      protein. When cows were implanted with blastocysts developed in the presence of
      GH from the morula stage, their pregnancy rate did not differ from that of the
      control. Increasing the glucose concentration in the medium from 1.5 mM to 3 mM
      starting at the morula stage (120 h after fertilization) slightly decreased the
      rate of development, but on the other hand, decreasing the glucose concentration
      to 0 mM did not affect either the rate of development or the cell number. Also,
      then GH had no effect on the developmental rate or the cell number in the absence
      of glucose. In conclusion, when the medium was supplemented with serum, GH
      improved embryo development from the morula stage, but an increased concentration
      of glucose decreased embryo development. Furthermore, GH did not improve the
      pregnancy rate of blastocysts developed in vitro.

PMID- 14967901
TI  - Successful production of blastocysts following ultrarapid vitrification with step
      wise equilibriation of germinal vesicle-stage mouse oocytes.
AB  - The purpose of this study was to evaluate the viability and subsequent
      developmental ability of murine germinal vesicle (GV) oocytes ultrarapidly
      vitrified after step-wise exposure to cryoprotectants (CPAs). Oocytes were
      transferred to a vitrification solution composed of 15% ethylene glycol, 15%
      dimethyl sulfoxide and 0.5 M sucrose in a direct manner (non-preequilibrium) or
      in a step-wise manner (single-, two-, or ten-step preequilibrium). After
      ultrarapid vitrification and storage in liquid nitrogen, the oocytes were thawed,
      washed by diluting the CPAs in five steps, and then subjected to in vitro
      maturation, fertilization and culture. In the non-preequilibrium group, the rates
      of post-thawed oocytes surviving, maturing to metaphase-II, developing to
      blastocysts and to hatching/hatched blastocysts were 91.8, 87.1, 15.9 and 2.3%,
      respectively. In the single- and two-step groups, the corresponding rates were
      97.0-98.2%, 92.2-95.0%, 22.0-29.4% and 8.8-15.6%, whereas in the ten-step group
      they were 98.2, 91.8, 38.6 and 22.8%, respectively. In the non-vitrified control
      group, the rates of oocytes maturing to metaphase-II, developing to blastocysts
      and to hatching/hatched blastocysts were 90.2, 75.2 and 51.5%, respectively. The
      present study shows that the ultrarapid vitrification of murine GV oocytes by a
      step-wise manner involving 10 steps preequilibrium may have an advantage in
      maintaining the viability and subsequent production of blastocysts.

PMID- 14967902
TI  - Caffeine in fertilization medium is not essential for bovine IVF by fully
      capacitated spermatozoa.
AB  - The purpose of this study was to examine: 1) whether caffeine in the
      fertilization medium under mineral oil is essential for bovine in vitro
      fertilization by fully capacitated spermatozoa, 2) the minimum concentration of
      caffeine that shows an adverse effect on the motility of preincubated
      spermatozoa. Cumulus-oocyte complexes with heterogeneous-appearing ooplasm were
      matured in in vitro culture for 24 h and used for insemination. The fertilization
      rates of the preincubated spermatozoa introduced into the fertilization medium
      containing 0 mM or 5 mM caffeine were examined. The fertilization rate of the
      spermatozoa introduced into the medium without caffeine (final concentration of
      caffeine at fertilization was 0.27-0.35 mM) was significantly higher than that in
      the medium with 5 mM caffeine (82.4% vs 55.2%, P<0.05). When the final
      concentration of caffeine at fertilization was reduced ten-fold (0.02-0.03 mM),
      the fertilization rate was not significantly improved (86.0%). The motility of
      the preincubated spermatozoa introduced into the fertilization medium containing
      0-5 mM caffeine was examined. The sperm motility in the fertilization medium
      without caffeine was significantly higher than that in the fertilization medium
      with more than 2 mM caffeine. These results indicate that caffeine in the
      fertilization medium is not essential for bovine in vitro fertilization by fully
      capacitated spermatozoa, and that more than 2 mM caffeine has an adverse effect
      on preincubated (capacitated) sperm motility.

PMID- 14967903
TI  - Comparison of the effectiveness of ovulation synchronization protocol in
      anestrous and cycling beef cows.
AB  - Applicability of ovulation synchronization protocol using GnRH and PGF(2alpha)
      (PGF) injection to anestrous beef cows remains controversial. We compared the
      effectiveness of the protocol in the anestrous stage of the beef cow with that in
      the cycling stage using the same animals. Ovaries of five Japanese Black and
      three Japanese Shorthorn cows were ultrasonographically examined, and blood
      samples were collected daily for hormonal analyses. Each animal received the
      protocol twice (Day -6 to -8: GnRH, Day 0: PGF, Day 2: GnRH). Additional blood
      samples were taken before and after GnRH injection for LH and FSH measurements to
      evaluate the pituitary function. For the ovarian status at the onset of the
      protocol cows were divided into anestrous (n=8) and cycling (n=8) stages. There
      was no significant difference in size of the dominant follicle at the first and
      second GnRH injections, and in the magnitude of the pituitary response to GnRH
      between the two stages. However, the size of the corpus luteum and progesterone
      concentrations at the PGF injection in the anestrous stage were significantly
      smaller and lower (P<0.01), respectively, and ovulation synchronization rate in
      the anestrous stage was significantly lower (P<0.05) than in the cycling stage.
      In conclusion, ovulation synchronization protocol in anestrous beef cows has
      limited effectiveness.

PMID- 14967904
TI  - Generation of transgenic rats expressing enhanced green fluorescent protein in
      gonadotropin-releasing hormone neurons.
AB  - Hypothalamic gonadotropin-releasing hormone (GnRH) neurons govern reproductive
      function by controlling the release of gonadotropins from the pituitary. To
      facilitate identification of living GnRH neurons, here we attempted to generate
      transgenic rats that express enhanced green fluorescent protein (EGFP) in GnRH
      neurons. About 3 kb of rat GnRH promoter region was inserted into the EGFP
      reporter cassette, and the expression of EGFP fluorescence was confirmed in
      several cell lines following transient transfection. Then we successfully
      generated a transgenic rat by injecting linearized GnRH-EGFP transgene into the
      pronuclei of fertilized oocytes. The GnRH-EGFP transgenic rats expressed EGFP in
      the brain, but not in the ovary, testis or thymus. Immunohistochemical
      examination revealed that detectable EGFP fluorescence was confined to the cell
      body of GnRH-immunoreactive neurons in the septum and preoptic area, while no
      EGFP signal was discernible in the median eminence where abundant GnRH
      immunoreactive fibers were observed. The mean percentage of EGFP-positive cells
      in the GnRH-positive cells was 76.3%. The GnRH-EGFP transgenic rats generated in
      the present study will enable characterization of properties of individual GnRH
      neurons.

PMID- 14967905
TI  - A passage and storage system for isolated bovine endometrial epithelial and
      stromal cells.
AB  - To establish a storage system for isolated endometrial cells, we investigated the
      basal, oxytocin (OT)- and tumor necrosis factor (TNF) alpha-stimulated production
      of prostaglandin (PG) F(2alpha) in bovine-passaged and frozen-thawed endometrial
      cells. Stromal and epithelial cells obtained from cows in the early stage of the
      estrous cycle (Days 2-5) were frozen at -80 C or further cultured and/or passaged
      until passage 4 in DMEM/Ham's F-12 supplemented with 10% calf serum. A fresh
      unfrozen primary culture and one-time passaged fresh-unfrozen cells were used as
      the control. When both unfrozen and frozen cells reached confluence, the culture
      medium was replaced with fresh medium with 0.1% BSA and the cells were stimulated
      with OT (100 ng/ml) or TNFalpha (1 ng/ml) for 4 h. The passage and freezing of
      the endometrial cells did not affect their morphology. In primary culture of
      frozen and unfrozen endometrial cells, OT strongly stimulated PGF(2alpha)
      production in epithelial cells, and TNFalpha strongly stimulated PGF(2alpha)
      production in stromal cells (P<0.05). The basal output of PGF(2alpha) in frozen
      stromal cells was similar to that in unfrozen stromal cells. However, the basal
      output of PGF(2alpha) in frozen epithelial cells was significantly lower than
      that unfrozen cells (P<0.05). On the other hand, in passaged cells, the basal
      level of PGF(2alpha) production was retained until passage 1 in epithelial cells,
      whereas it was retained until passage 4 in stromal cells. Although epithelial
      cells responded to OT in PGF(2alpha) production until passage 2 (P<0.05), the
      stromal cells showed a significant response to TNFalpha until passage 4 (P<0.05).
      These results suggest that stored cells could be used for studying the physiology
      of bovine endometrium in vitro until passage 1 in endometrial epithelial cells,
      and until passage 4 in stromal cells.

PMID- 14967906
TI  - Effects of in utero exposure to bisphenol A on expression of RARalpha and
      RXRalpha mRNAs in murine embryos.
AB  - Retinoic acid receptor (RAR) alpha and retinoid X receptor (RXR) alpha are key
      factors in a nuclear receptor-dependent signal. To evaluate the effects of
      bisphenol A (BPA), a candidate endocrine disruptor (ED), on embryonic
      development, we examined the mRNA levels of RARalpha and RXRalpha in murine
      embryos, exposed in utero to BPA (2 microg/kg/day) at 6.5-17.5 days post-coitum
      (dpc), by the real-time reverse transcription-polymerase chain reaction (RT-PCR)
      method. Higher levels of RARalpha mRNA in cerebra of male and female embryos of
      control groups were detected at 14.5 dpc. In utero BPA reduced the RARalpha mRNA
      expression. Higher levels of RXRalpha mRNA in cerebra of male and female embryos
      were seen at 12.5 dpc. The exposure decreased RXRalpha mRNA expression in male
      but not female embryos. No remarkable change in the RARalpha mRNA expression
      level was noted in cerebella of male or female embryos of the control group
      during embryonic development. Exposure to BPA increased expression levels of
      RARalpha mRNA in cerebella of male and female embryos at 12.5 dpc. Higher levels
      of RXRalpha mRNA in cerebella of male and female embryos were seen, but no
      remarkable changes were noted during embryonic development. BPA significantly
      decreased the expression levels of RXRalpha mRNA in cerebella of female embryos
      at 12.5, 14.5 and 18.5 dpc. RARalpha and RXRalpha mRNAs were expressed in gonads
      (testes and ovaries) of murine embryos from 12.5 to 18.5 dpc. In utero exposure
      to BPA decreased levels of RARalpha mRNA in testes of 14.5- and 18.5-dpc-embryos,
      levels of RXRalpha mRNA in testes of 14.5-dpc-embryos, and levels of RXRalpha
      mRNA in ovaries of 14.5-dpc-embryos. The present findings indicate that RARalpha
      and RXRalpha play crucial roles in organogenesis, and the growth and development
      of murine embryos, and will contribute to the assessment of the toxic effects of
      BPA on retinoid signals in embryogenesis.

PMID- 14967907
TI  - Expression analyses of sex steroid-regulated genes in neonatal rat hypothalamus.
AB  - Estrogen plays an important role in sexual differentiation of the brain in rats
      during the perinatal period. To elucidate molecular mechanisms underlying sexual
      differentiation of the brain, in this study we investigated genes differentially
      expressed between sexes or induced to express by estrogen in neonatal rat
      hypothalamus using DNA microarray analysis in combination with real-time RT-PCR.
      It was found that the levels of expression of the genes encoding glutamic acid
      decarboxylase 65 and coronin 1b were higher in male than female hypothalamus on
      postnatal day (PN) 5 and those of collagen type 3 alpha1 and thioredoxin
      reductase 2 genes in female hypothalamus on PN5 were decreased and increased,
      respectively, by treatment with estradiol on PN2. Then the developmental changes
      in the expression of these 4 genes were examined from 1 day before the
      parturition to PN9, and they all showed sexual dimorphic patterns. In addition,
      dependence of the expression of these genes on either estradiol, testosterone or
      dihydrotestosterone during the neonatal period was confirmed. These results
      suggest that these four genes are involved in sexual differentiation of the rat
      brain, and that androgen per se as well as estrogen may take part in the
      processes.

PMID- 14967908
TI  - Proliferative potential of endometrial stromal cells, and endometrial and
      placental expression of cyclin in the bovine.
AB  - The objective of the present investigation was to study proliferative activity of
      fibroblast-like endometrial stromal cells in bovine endometrial caruncular (CAR)
      and intercaruncular (ICAR) areas that have distinct functions during
      implantation. Endometrial stromal cells were derived from CAR and ICAR of
      nonpregnant cows, and their proliferative potential was analyzed in an in vitro
      cell culture system. In addition, expression of four types of cell cycle
      regulatory molecules was analyzed by RT-PCR in samples of CAR, ICAR, cotyledon
      (COT) and fetal membrane of both artificially inseminated (AI) and somatic
      nuclear transferred (NT) cows on days 30 and 60 of gestation. The proliferation
      growth curve showed that the cells derived from CAR had higher proliferative
      activity than that of ICAR-derived cells. No morphological differences were found
      between the cells derived from CAR and ICAR at population-doubling levels (PDL)
      of the two. Most of the cells derived from ICAR of nonpregnant cows exhibited
      expanded shape with no further proliferation at PDL 6 with a lack of cyclin E
      expression. Of the regulatory molecules, cyclin D1, CDK2 and CDK4 were expressed
      in both CAR and ICAR cells derived from both nonpregnant, and AI cows on days 30
      and 60 of gestation. The expression of cyclin E in both AI and NT cows was
      confined to COT and fetal membrane on day 30 of gestation. Cyclin E expression on
      day 60 of gestation in AI cows was observed in all but ICAR areas. In marked
      contrast, however, cyclin E expression on day 60 of gestation in NT cows was
      confined to COT, suggesting that poor placentation in these cows is possibly
      associated with a lack of cyclin E expression. These results suggest that CAR
      derived stromal cells have higher proliferative potential, which may be related
      to cyclin E expression during implantation.

PMID- 14967909
TI  - The biomarker and endocrine disruptors in mammals.
AB  - The compounds that bind steroid hormone receptors including estrogen receptors
      (ERs), progesterone receptor (PR) or androgen receptor (AR), and induce or
      modulate a steroid hormone receptor-mediated response could be defined as
      endocrine disruptors (EDs). Currently, there are no standard methods to determine
      whether a chemical is an endocrine disruptor or not. Most results of in vitro and
      in vivo data are derived from assays that measure estrogenic activity, thus fewer
      data are available from assays that measure androgenic and progestogenic
      activities. In this review, we introduce a novel in vivo model to detect EDs
      using immature rats in the induction of Calbindin-D(9k) (CaBP-9k) mRNA and
      protein by estrogenic compounds. In addition, we summarize other biomarkers and
      screening methods for EDs in mammals to describe the usefulness of indicated
      biomarkers, although mammalian models are very few based on experimental
      findings.

PMID- 14967910
TI  - Molecular mechanisms underlying pig oocyte maturation and fertilization.
AB  - Since the pig is not only an important farm animal, but also a model animal for
      biomedical applications, the development of reproductive technologies in this
      species has been very important. In vitro oocyte maturation and fertilization
      (IVM-IVF) are basic techniques for a number of oocyte- or embryo-related
      technologies. The practical aspects for pig oocyte IVM-IVF have been reviewed,
      while the molecular mechanisms underlying oocyte meiotic maturation and
      fertilization have not been well summarized, although accumulating data have been
      obtained in recent one decade. This review will focus on what is known about the
      molecular mechanisms of porcine oocyte maturation and fertilization such as first
      meiosis resumption, meiotic spindle assembly, second meiosis metaphase (MII)
      arrest during oocyte maturation, sperm-egg recognition and fusion, sperm acrosome
      reaction, second meiosis resumption, sperm chromatin decondensation, and
      pronucleus formation during fertilization, as well as the establishment of
      polyspermy block.

PMID- 14967911
TI  - Allometric study on the relation between the growth of preantral and antral
      follicles and that of oocytes in bovine ovaries.
AB  - We examined the relation between the growth of preantral and antral follicles and
      that of their oocytes in the ovaries of Holstein cows. We recovered follicles and
      oocytes (419 pairs) from the ovaries of 61 cows, and examined the relative growth
      relating the follicle diameter to the oocyte diameter by using six regression
      models for only healthy oocytes and all the oocytes including degenerated ones
      with and/or without zona pellucida. The best fitting model was found to be a
      hyperbolic regression (R(2): 0.999). The differentiated equation for the
      hyperbolic curve in normal oocytes with zona pellucida and the follicles was
      found to be y'=41.0/(x+0.253) (2): y and x are diameters of oocytes (microm) and
      follicles (mm), respectively. When follicles grew more than 4.0 mm in diameter,
      the growth rate of the oocytes calculated by the differentiation equation was
      found to be an asymptotic depression around zero. Thus, it is suggested that when
      the follicles grow more than 4.0 mm in diameter, the oocytes reach full size and
      cease to grow. Furthermore, it is considered that the equation can be applied to
      the assessment of normal growth in oocytes and follicles cultured in vitro.

PMID- 14967912
TI  - Plasma concentration of estrone sulfate during pregnancy in different breeds of
      Japanese beef cattle.
AB  - Plasma concentrations of estrone sulfate in different breeds of Japanese beef
      cattle and the relationship between those concentrations and feto-placental
      growth were examined in order to assess the possibility of monitoring abnormal
      growth of the fetus. Blood samples were obtained from cows from day 90 of
      gestation to parturition. The plasma concentration of estrone sulfate was
      measured by direct enzyme immunoassay. From day 180 of gestation, the mean
      concentration of estrone sulfate increased gradually and it was drastically
      elevated after day 240 of gestation with the maximum at day 285. Plasma
      concentrations of estrone sulfate on day 240 of gestation was significantly
      increased in F(1) cows (Holstein Friesian and Japanese Black) compared with those
      in other breeds of cow. From day 270 to 278 of gestation, estrone sulfate
      concentrations of Holstein Friesian cows inseminated by Holstein Friesian
      differed from those inseminated by Japanese Black. In the cow with retained
      placenta, the plasma concentration of estrone sulfate reached plateau at day 240
      of gestation and did not increase thereafter. There was no significant
      relationship between estrone sulfate concentration and duration of gestation,
      calf birth weight, weight of placenta or viability of newborn calves. These
      results indicate that changes of plasma estrone sulfate concentration in Japanese
      beef cattle are very similar to those in Holstein dairy cattle. They also suggest
      that the plasma concentration of estrone sulfate is associated with the breed of
      pregnant cow and that its concentration is also affected by calf birth weight
      depending on the breed of bull. It seems possible to predict the incidence of
      retained placenta but not the calf birth weight and viability of newborn calves
      in Japanese beef cattle.

PMID- 14967913
TI  - Immunocytochemical identification of Pit-1 containing cells in the anterior
      pituitary of hens.
AB  - Our goal was to identify the cells expressing Pit-1 protein in chicken anterior
      pituitary. The anterior pituitaries were collected from laying hens after
      perfusion with formalin-PBS, and fixed with Bouin's fixative followed by paraffin
      embedding. Sections of the anterior pituitaries were immunostained for Pit-1 in
      the first staining sequence followed by staining for 6 types of pituitary
      hormones in the second sequence. Pit-1 positive nuclei were observed in the
      glandular cells in both the cephalic and caudal lobes. Pit-1 immunoreaction
      products were colocalized in the glandular cells immunopositive for growth
      hormone, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing
      hormone, adrenocorticotropic hormone or prolactin. These results indicate that
      Pit-1 protein induction occurs in 6 types of glandular cells, suggesting that Pit
      1 may regulate hormone synthesis in each glandular cell in the chicken pituitary.

PMID- 14967914
TI  - Effects of body condition score in cows peripartum on the onset of postpartum
      ovarian cyclicity and conception rates after ovulation synchronization/fixed-time
      artificial insemination.
AB  - The aim of this study was to examine whether the nutritional state of cows
      peripartum was associated with the recovery of ovarian function and conception
      rates after synchronization of ovulation and fixed-time artificial insemination
      (OVSYNCH/TAI). The effect of the interval in days from calving to the first
      ovulation on conception rates after OVSYNCH/TAI was also investigated. Conception
      rates of cows after OVSYNCH/TAI (n=39) were 43.6%. The conception rates of cows
      with a body condition score (BCS) of 2.75-3.25 at 30 d postpartum and on the day
      of OVSYNCH treatment were significantly higher than in cows with a BCS < or =2.5
      (P<0.05). The percentage of cows establishing ovarian cyclicity before 55 d
      postpartum in cows with a BCS of 2.75-3.25 at 30 d postpartum and on the day of
      OVSYNCH treatment were significantly higher than in cows with a BCS < or =2.5
      (P<0.05). The conception rates after OVSYNCH/TAI in cows which recovered ovarian
      cyclicity within 34 d postpartum were significantly higher than in cows with
      first ovulation > or =56 d (P<0.05). These results indicated that the nutritional
      state in cows peripartum influenced the conception rates after OVSYNCH/TAI and
      the postpartum ovarian cyclicity and also suggested that the conception rates
      after OVSYNCH/TAI decreased in cows with delayed recovery of ovarian cyclicity.

PMID- 14967915
TI  - Effects of 17beta-estradiol and tamoxifen on the selenoprotein phospholipid
      hydroperoxide glutathione peroxidase (PHGPx) mRNA expression in male reproductive
      organs of rats.
AB  - The selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) is
      highly expressed in testes under gonadotropin control. The expression patterns of
      PHGPx mRNA by 17beta-estradiol (E2) as an estrogen and tamoxifen (Tam) as an
      estrogen antagonist were investigated in the reproductive organs of male rats.
      Twelve-week-old male Sprague-Dawley rats were subcutaneously injected with E2
      (7.5 microg/kg/day) or Tam (5 mg/kg/day) for 1 week. The E2 treatment
      significantly increased the levels of PHGPx mRNA in both testes and prostates,
      whereas the Tam treatment significantly decreased the levels of PHGPx mRNA,
      compared to the vehicle control (p<0.01). The treatment with E2 or Tam slightly
      decreased the levels of PHGPx mRNA in epididymides. In histopathological
      examination, severe vacuolization and depletion of germ cells in the seminiferous
      tubules, cell debris in the tubular lumen, and mild proliferative changes in
      interstitial tissues were observed in the testes of Tam-treated rats, whereas
      only mild spermatogonial proliferation was observed in the seminiferous tubules
      of E2-treated rats. There were no typical histopathological changes in the
      epididymides of any of the laboratory rats but mild epithelial proliferation in
      the prostates of E2- and Tam-treated rats. These results suggest that PHGPx mRNA
      expression may be influenced by estrogen in the male reproductive organs.

PMID- 14967916
TI  - Identification of GABABR2 in rat testis and sperm.
AB  - GABA is capable of mimicking and potentiating the action of progesterone in
      initiating the acrosome reaction (AR) of mammalian sperm. The GABA-initiated AR
      is mediated by GABA(A)R; whereas GABA(B)R1 protein found in rat testis and sperm
      tends to modify this process. Moreover, the occurrence of GABA(B)R2, a subunit
      essential for the formation of a functionally active GABA (B)R, in rat testis and
      sperm has not been established. In the present study, rat testis and sperm were
      analyzed for the presence of GABA(B)R2 transcript and protein by RT-PCR, Northern
      blot, Western blot and an indirect immunofluorescence technique. Northern blot
      shows that the transcript of testis GABA(B)R2 is shorter (~3.0 Kb) than that of
      the brain (~5.6 Kb). The full length testis GABA(B)R2 cDNA was prepared by RACE
      PCR and found to be shorter by 2.2 Kb in the segment at the extreme terminus of
      3'UTR of rat brain GABA(B)R2 but, the sequences corresponding to the open reading
      frame and 5'-UTR of rat testis GABA(B)R2 were found to be identical to those of
      rat brain. GABA(B)R2 protein isolated from rat epididymal sperm was slighter
      larger than those of rat testis and brain. It was principally localized in the
      acrosome region of the head of rat sperm by an indirect immunofluorescence
      technique. The present results establish that GABA(B)R2 protein is produced in
      rat testis and sperm and may play a role in GABA triggering of AR.

PMID- 14967917
TI  - Effects of vinclozolin administration on sperm production and testosterone
      biosynthetic pathway in adult male rat.
AB  - The effect of vinclozolin (VCZ), used as a fungicide and known to have anti
      androgenic effects on spermatogenesis and gene expression in the male rat testis
      was investigated. In Experiment 1, VCZ (100 mg/kg/day) or flutamide (FM, 25
      mg/kg/day) was orally administered to male Holzman rats for six days. 8 days
      after the last administration (D8), a drastic increase in intratesticular
      testosterone was detected in FM (4.2-fold over control) but not in VCZ treated
      animals, whereas on D36 post-administration, both groups showed similar levels.
      Significant decreases in daily sperm production were seen in both VCZ and FM
      treated rats on D36. Semiquantitative RT-PCR analysis with testicular and
      pituitary mRNAs on D8 revealed that LHbeta and FSHbeta mRNAs were increased in
      the pituitary by VCZ, as well as by FM. Among the four testicular steroidogenic
      enzyme genes, cytochrome P450 side chain cleavage (P450scc) and cytochrome P450
      17alpha/C(17-20) lyase (P450c17) mRNAs were significantly increased, whereas
      17beta-hydroxysteroid dehydrogenase type III (17betaHSD) mRNA was not changed. A
      significant increase in 3beta-hydroxysteroid dehydrogenase type I (3betaHSD) and
      a decrease in androgen receptor (AR) mRNA were observed only in FM treated rats.
      Immunohistochemistry demonstrated intense staining of P450scc in the interstitial
      cells of VCZ-treated testis on D8. In Experiment 2, hormone levels were measured
      at 1, 3, 6, 12 and 24 hours after VCZ (100 mg/kg) administration to Sprague
      Dawley rats. Serum LH level remained constant for the first 3 hours and started
      to increase at 6 hrs. In contrast, serum and intratesticular testosterone levels
      increased 2-fold at 1 hr and maintained the level until 24 hrs. P450c17 mRNA
      level was 2-fold increased at all periods, whereas no obvious changes were
      detected in the other steroidogenic enzyme genes. Although not statistically
      significant, AR mRNA level increased 2-fold, 3 hrs after VCZ administration.
      These results indicate that VCZ affects the pituitary in a similar manner as FM,
      but functions differently on testicular gene expression.

PMID- 14967918
TI  - Interactions between the oocyte and surrounding somatic cells in follicular
      development: lessons from in vitro culture.
AB  - Mammalian oogenesis occurs concomitantly with folliculogenesis in a coordinated
      manner in the ovaries. In vitro growth (IVG) culture systems of the oocytes have
      been developed as a new technology for utilizing incompetent oocytes in the ovary
      as a source of mature oocytes as well as for studying oogenesis,
      folliculogenesis, and oocyte-somatic cell interactions. The results of IVG
      experiments have suggested that direct association of oocytes and surrounding
      granulosa cells supports oocyte viability and growth through the gap junctions,
      which are efficient conduits for low molecular weight substances. It has been
      revealed that granulosa cells metabolize some molecules which are in turn
      transported into the oocytes. IVG systems have also provided evidence that FSH
      promotes the development of follicles at secondary or later stages by its
      stimulation of proliferation and differentiation of granulosa cells, and perhaps
      by its anti-apoptotic effects. In addition, interactions between granulosa cell
      derived KIT ligands and oocyte KIT receptors have been suggested as initiating
      oocyte growth and follicular development. Furthermore, recent findings suggest
      there are growth factors derived from oocytes such as GDF-9 and BMP-15. With such
      factors, oocytes participate in follicular development by regulating the
      differentiation of surrounding somatic cells. These bidirectional communications
      between oocytes and somatic cells are important for oocyte growth and follicular
      development. IVG systems should provide further information regarding oogenesis
      and folliculogenesis in the ovary.

PMID- 14967919
TI  - Intracytoplasmic sperm injection in the pig: where is the problem?

PMID- 14967920
TI  - Alterations of gene expression in adult male rat testis and pituitary shortly
      after subacute administration of the antiandrogen flutamide.
AB  - In the course of profiling alterations of gene expression in the male
      reproductive system induced by anti-androgenic agents, 28 genes expressed in the
      testis or pituitary of adult rats were examined shortly after subacute
      administration of the well-known anti-androgen, flutamide (FM). FM (25 mg/kg/day)
      was orally administered to male rats for six days. On day 8 (D8) after the first
      dose of FM, intratesticular testosterone (T) levels had dramatically increased,
      but daily sperm production on D36 was significantly decreased. The mRNA levels of
      testicular and pituitary genes on D8 were measured by semiquantitative RT-PCR.
      Among the six testicular steroidogenic enzyme genes, the mRNAs of the P450 side
      chain cleavage, P450 17 alpha/C(17-20) lyase, and 3beta-hydroxysteroid
      dehydrogenase type I (3betaHSD) genes significantly increased, whereas 17beta
      hydroxysteroid dehydrogenase type III slightly decreased. Among the three steroid
      receptors examined, androgen receptor (AR) and glucocorticoid receptor (GR) mRNAs
      were significantly down-regulated (29% and 35%, respectively) in the testis, but
      there was no change in estrogen receptor alpha. There were no clear changes in
      expression of the gonadotropin receptors and Sertoli cell specific genes, but a
      slight increase was observed in expression of the lactose dehydrogenase-c mRNA, a
      germ cell specific gene. Among the three immediate early genes, c-myc mRNA was
      increased approximately 1.4-fold. In the pituitary, on the other hand, mRNAs for
      LHbeta and FSHbeta subunits and gonadotropin releasing hormone receptor had
      increased significantly. These results show that subacute FM administration first
      affected hypothalamus/pituitary hormone gene expression, then altered
      gonadotropin secretion, and subsequently induced over-expression of testicular
      steroidogenic enzyme genes. However, the significant up-regulation of 3betaHSD
      and down-regulation of AR mRNAs, despite the higher level of intratesticular T,
      might be explained by an antagonistic action of hydroxyflutamide retained in the
      testis. The profiles of alterations in gene expression observed will provide
      important information for the screening of adult male animals for anti-androgenic
      chemicals.

PMID- 14967921
TI  - Comparison of luteinizing hormone and steroid hormone secretion during the peri-
      and post-ovulatory periods in Mangalica and Landrace gilts.
AB  - The objective of this study was to determine plasma concentrations of luteinizing
      hormone (LH), progesterone (P4) and estradiol-17beta (E2) in Mangalica gilts (M),
      a Hungarian native breed, and compare them with Landrace gilts (L) during the
      peri- and post-ovulatory periods. The estrous cycle of gilts was synchronised by
      Regumate feeding, and ovulation was induced with a gonadotropin-releasing hormone
      (GnRH) agonist. Blood sampling was carried out via indwelling jugular catheters
      three times a day and in 2-h intervals during a 16-h period after the GnRH
      application. The concentrations of LH, E2 and P4 were determined by immunoassays.
      Gilts of both breeds showed a typical gonadotropin and gonadal hormone secretion
      pattern. Preovulatory E2 peaks were observed on day 2 (M) and day 4 (L) after the
      last Regumate feeding. Highest E2 concentration was different between M and L
      breeds (46.5 +/- 5.7 vs. 26.0 +/- 6.8 pg/ml, P < 0.05). Maximum LH levels
      measured up to 6 h after GnRH were not different between M and L breeds (11.5 +/-
      4.1 vs. 6.6 +/- 2.3 ng/ml). Both LH amounts during surge (41.1 +/- 15.9 vs. 27.5
      +/- 6.1 ng/ml) and total over LH release (73.4 +/- 22.2 vs. 50.0 +/- 8.7 ng/ml)
      did not differ significantly between M and L breeds. P4 concentrations started to
      rise on day 6 after Regumate feeding and increased significantly from 0.6 +/- 0.3
      and 0.7 +/- 0.4 ng/ml to maximal 14.0 +/- 2.4 and 11.3 +/- 2.1 ng/ml in M and L
      breeds, respectively. Mean P4 secretion was higher in M on days 10-15 (12.9 +/-
      2.6 vs. 9.3 +/- 2.2 ng/ml; P<0.05). At the same time the number of corpora lutea
      was lower in M compared to L (10.3 +/-1.5 vs. 17.8 +/- 5.0, P<0.05). In our
      experiment, there was no evidence that differences in the secretion of analysed
      hormones during the peri- and post-ovulatory periods are a possible cause of
      usually lower fecundity in Mangalica gilts.

PMID- 14967922
TI  - Possible role of interferon-tau on in vitro development of bovine embryos.
AB  - The effect of interferon-tau on in vitro development of bovine embryos was
      investigated. After in vitro fertilization, embryos developed to the morula stage
      were cultured for 3 days in TCM-199 or CR1 medium containing BSA or FCS
      supplemented with or without recombinant IFN-tau produced by a baculovirus
      expression system. Addition of baculovirus-expressed IFN-tau (100 ng/ml)
      significantly promoted development to the blastocyst stage in both culture media.
      Addition of E. coli expressed IFN-tau (2 microg/ml) also significantly promoted
      the embryonic development. Supplementation of BSA or FCS did not affect the
      growth-promoting effect of IFN-tau. To determine whether the growth-promoting
      effect of IFN-tau is related to the interferon type I receptors that bind to type
      I interferon such as IFN-alpha, embryos were cultured with IFN-alpha. Although
      IFN-alpha significantly promoted the development, a much higher concentration (25
      microg/ml) was required than IFN-tau. A reverse transcription polymerase chain
      reaction analysis revealed the expression of mRNA encoded type-I IFN receptor
      subunit from morula to blastocyst stage embryos. The overall results suggest a
      novel function for IFNs in promoting embryonic development and the effect may be
      related to type-I IFN receptor expressed in the early stages of preimplantation
      embryos.

PMID- 14967923
TI  - A PCR-based sex determination method for possible application in caprine gender
      selection by simultaneous amplification of the Sry and Aml-X genes.
AB  - Sex determination of livestock is performed to achieve the objectives of
      livestock breeding programmes. Techniques for sex determination have evolved from
      karyotyping to detecting Y-specific antigens and recently to the polymerase chain
      reaction (PCR), which appears to be the most sensitive, accurate, rapid and
      reliable method to date. In this study, a PCR-based sex determination method for
      potential application in goat breeding programmes was developed. Primers were
      designed to amplify a portion of the X amelogenin gene (Aml-X) on the X
      chromosome to give a 300 bp product and Sry gene on the Y chromosome to give a
      116 bp product. PCR optimization was performed using DNA template extracted from
      a whole blood sample of Jermasia goats (German Fawn x Katjang) of both sexes. It
      was possible to identify the sex chromosomes by amplifying both male- and female
      specific genes simultaneously in a duplex reaction with males yielding two bands
      and females yielding one band. The Aml-X primer set, which served as an internal
      control primer, did not interfere with amplification of the Y-specific sequence
      even when a low amount of DNA (1 ng) was used. The duplex reaction subjected to a
      blind test showed 100% (14/14) concordance, proving its accuracy and reliability.
      The primer sets used were found to be highly specific and were suitable for
      gender selection of goats.

PMID- 14967924
TI  - Roles of tumor necrosis factor-related apoptosis-inducing ligand signaling
      pathway in granulosa cell apoptosis during atresia in pig ovaries.
AB  - To reveal the molecular mechanism of selective follicular atresia in porcine
      ovaries, we investigated the changes in the expression of tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) and its receptor (DR4) proteins and
      TRAIL mRNA in granulosa cells during follicular atresia. Immunohistochemical,
      Western immunoblotting and reverse transcription-polymerase chain reaction
      analyses (RT-PCR) revealed that significant increases in TRAIL protein and mRNA
      levels but not DR4 protein were changed during atresia. The RT-PCR product was
      confirmed to be porcine TRAIL by the cDNA sequence determination. An in vitro
      apoptosis inducing assay using cultured granulosa cells prepared from healthy
      follicles showed that TRAIL could activate caspase-3 and induce apoptotic cell
      death in the cells. The present findings confirm that TRAIL induces apoptosis in
      granulosa cells during atresia in porcine ovaries.

PMID- 14967925
TI  - Dynamic changes in the expression of protein tyrosine phosphatases during
      preimplantation mouse development: semi-quantification by real-time PCR.
AB  - Protein tyrosine phosphatase (PTP) expression was examined in preimplantation
      mouse embryos. We previously reported that SHP-2, LAR, PTPT9, SHP-1, and mRPTPB
      were expressed in preimplantation mouse embryos. Here, we examined changes in the
      expression levels of these PTPs during preimplantation development. cDNA was
      obtained by reverse transcription of embryo mRNA, amplified with 10 PCR cycles,
      and then subjected to real-time fluorescence-monitored PCR. Experiments with an
      mRNA dilution series revealed that the data obtained matched the quantities of
      mRNA used. The measurements obtained with real-time fluorescence-monitored PCR
      showed that the expression of each PTP mRNA changed dynamically, and that each
      had a different expression pattern. This suggests that PTPs are involved in the
      regulation of growth and differentiation during preimplantation development.

PMID- 14967926
TI  - Effects of oral exposure of bisphenol A on mRNA expression of nuclear receptors
      in murine placentae assessed by DNA microarray.
AB  - Bisphenol A (BPA), a candidate endocrine disruptor (ED), is considered to bind to
      estrogen receptors and to regulate expressions of estrogen responsive genes. It
      has also shown evidence of affecting the reproductive, immunological and nervous
      systems of mammalian embryos. However, the effects of BPA on placentae, a central
      organ of feto-maternal interlocution, are still unclear. To reveal the mechanisms
      of BPA effects on placentae in mammals, we compared the mRNA expression of 20
      nuclear receptors between placentae of vehicle controls and those of orally BPA
      exposed pregnant mice by a DNA microarray technique. In murine placentae, mRNAs
      of 11 nuclear receptors were not detected. However, greater than 1.5 fold changes
      in mRNA expression of nine nuclear receptors between vehicle control and BPA
      treated mice were noted. Moreover, remarkable changes in mRNA expression of six
      non-nuclear receptor proteins were induced by BPA exposure. There were various
      differences in the effects of BPA on the expression of these mRNAs between the
      placentae with male embryos and those with female embryos. Such embryo-sex
      dependent differences are interesting and important pointers to understanding of
      the endocrine disrupting effect of BPA. The present data indicate that BPA
      affects the expression of nuclear receptor mRNAs in placentae and may disrupt the
      physiological functions of placentae.

PMID- 14967927
TI  - Follicular microvasculature and angiogenic factors in the ovaries of domestic
      animals.
AB  - The genetic and molecular mechanisms that control the development of capillary
      blood vessels during follicular development are beginning to be elucidated.
      Ovarian follicles contain and produce angiogenic factors that may act alone or in
      concert to regulate the process of thecal angiogenesis. These factors are
      ultimately controlled by endocrine, paracrine and autocrine regulation. A recent
      study indicated that vascular endothelial growth factor (VEGF) plays an important
      role in the process of thecal angiogenesis during follicular development. We are
      developing a novel technology for the induction of follicular development using
      the technique of in vivo gene administration. Here, we summarize the recent
      progress of our research.

PMID- 14967928
TI  - Evaluation of bovine embryos produced in high performance serum-free media.
AB  - This review evaluates the quality of bovine embryos developed from in vitro
      matured (IVM) and -fertilized (IVF) oocytes cultured in either serum-free or
      serum-containing media. Bovine embryos cultured in serum-supplemented medium
      contain numerous cytoplasmic lipid droplets and immature mitochondria compared to
      those cultured in serum-free medium. The accumulation of cytoplasmic lipids in
      embryos developed in serum-containing medium may be a result of incorporation of
      lipoproteins from the serum and may result in impaired function of mitochondria.
      The improved serum-free media (IVMD101 and IVD101) offer several advantages over
      culture in serum-containing medium, including increased rates of blastocyst
      formation and higher cell numbers. Additionally, the survival and hatching rates
      of embryos produced in serum-free media after post-thaw culture were superior to
      those of embryos produced in the serum-containing medium, suggesting that the
      abnormal accumulation of cytoplasmic lipids in embryos may have a negative effect
      on the sensitivity of embryos to chilling and freezing. These serum-free culture
      systems have proven to be beneficial for the production of good quality embryos
      from IVM-IVF bovine oocytes. Furthermore, recent studies have shown a correlation
      between mitochondrial function (oxygen consumption) and embryo quality. A new
      method using scanning electrochemical microscopy may be capable of assessing the
      viability and developmental potential of bovine embryos.

PMID- 14967929
TI  - Messenger ribonucleic acid expressions of hepatocyte growth factor, angiopoietins
      and their receptors during follicular development in gilts.
AB  - Angiogenic factors are associated with angiogenesis during follicular development
      in the mammalian ovary. The aim of the present study was to determine the
      relationships between the vascular network and mRNA expressions of angiopoietins
      (Ang)-1, Ang-2 and hepatocyte growth factor (HGF), and their receptors in
      follicles at different developmental stages during follicular development.
      Ovaries in gilts were collected 72 h after equine chorionic gonadotropin (eCG,
      1250 IU) treatment for histological observation of the capillary network.
      Granulosa cells and thecal tissues in small (<4 mm), medium (4-5 mm) or large (>5
      mm) individual follicles were collected for detection of mRNA expression of HGF,
      Ang-1 and Ang-2 in granulosa cells, and HGF receptor (HGF-R) and Tie-2 in the
      theca cells by semi-quantitative RT-PCR. The number of capillaries in the thecal
      cell layer increased significantly in healthy follicles at all developmental
      stages in the eCG group compared with those in controls. The expression of Ang-1
      mRNA declined in granulosa cells of medium and large follicles and the level of
      Ang-2 mRNA increased in granulosa cells of small follicles after eCG treatment.
      The ratio of Ang-2/Ang-1 increased in small, medium and large follicles from
      ovaries after eCG treatment, but Tie-2 mRNA expression in the theca cells did not
      change. The level of HGF mRNA increased in granulosa cells of small follicles
      after eCG treatment but HGF-R in theca cells was not increased by eCG. These data
      suggested that the angiopoietins might be associated with thecal angiogenesis
      during follicular development in eCG-treated gilts.

PMID- 14967930
TI  - Establishment of feather follicle stem cells as potential vehicles for delivering
      exogenous genes in birds.
AB  - The present study was performed to develop a culture system for feather
      keratinocyte stem cells to enable the genetic manipulation of endangered avian
      species. The feather follicle cells were isolated from growing feathers of adult
      White Leghorn chicken. Leukemia inhibitory factor (LIF) was used to maintain the
      characterization of the keratinocyte colony-forming cells (KCFCs). The EGFPN1
      plasmid DNA retroviral vector was used to deliver Green Fluorescent Protein (GFP)
      gene, which was introduced to the KCFCs by lipofection. After removal of the
      fibroblast-like cells, the feather KCFCs attached to the substrate within 24 h of
      seeding. The cells continued to proliferate for at least 30 days in the presence
      of LIF. The cell-adhesion molecules such as integrin beta1 and CD49c were
      immunocytochemically positive in the cells. The KCFCs differentiated into
      barbular cells and pennaceous feather vane in the LIF-free medium. The GFP gene
      transfected KCFCs stably expressed GFP. The present results indicate that the
      KCFCs derived from feather follicles are closely related to multipotent stem
      cells. In addition, gene manipulation of such stem cells may be useful for the
      production of chimera in avian species.

PMID- 14967931
TI  - Histological study of the hypertrophic placentas and open eyelids observed in
      cloned fetuses.
AB  - Mice cloned from somatic or ES cells showed signs of phenotypically various
      abnormalities. These abnormalities are now considered to result from aberrant
      gene expressions by epigenetic reprogramming errors but it is still unclear when
      these abnormalities occur and what histological changes occur during the
      gestation period. To address these issues, we histologically examined the
      hypertrophic placentas and open eyelids at 12.5, 17.5 and 19.5 days of the
      gestation period in ES-derived cloned mice that we have previously reported. In
      the placentas, the histology revealed that the hypertrophy had already occurred
      at 12.5 dpc and that the main change was the proliferation of trophoblast cells
      in the labyrinth layer. In the fetuses and placentas at 17.5 and 19.5 dpc,
      extensive proliferation of spongiotrophoblast and glycogen cells in the
      spongiotrophoblast layer and enlarged trophoblast giant cells were observed. Open
      eyelids in cloned mice were observed from 17.5 dpc, whereas the eyelids of the
      control mice had already been closed. The histology showed the malformation of
      eyelids where the formation of the stratum corneum and stratum granulosum in the
      epidermis was insufficient. Based on the histology described here, further
      comparative studies of the gene expression and histology of abnormalities seen in
      cloned mice and in gene-targeted and spontaneously mutated mice with similar
      phenotypic abnormalities could help illuminate these abnormalities and could
      contribute to the development of somatic cloning technology.

PMID- 14967932
TI  - Immunohistochemical localization of 3beta-hydroxysteroid dehydrogenase in the
      granulosa and theca interna layers of bovine cystic follicles.
AB  - The aim of the present study was to determine whether the alteration of
      population of cells containing 3beta-hydroxysteroid dehydrogenase (3beta-HSD) is
      responsible for the formation of cystic follicles. Paraffin sections of healthy
      (2 to 5 mm in diameter), atretic (2 to 5 mm) and cystic follicles (more than 25
      mm) were immunohistochemically stained with rabbit polyclonal antibody to bovine
      3beta-HSD. The 3beta-HSD-positive cells were counted in 4 different regions of
      the follicles from the apical to the basal side. The frequencies of 3beta-HSD
      positive granulosa cells in cystic follicles were significantly higher than those
      in the healthy follicles (P<0.05), although the number of 3beta-HSD-positive
      granulosa cells in the cystic follicle were fewer than half the cells (30 to 40%)
      and was much smaller than that in preovulatory follicles (Conley et al., 1995).
      The frequencies of 3beta-HSD-positive cells were higher in the granulosa layer
      and lower in the theca interna layer of the cystic follicles than the atretic
      follicles. These results suggest that the differentiation of granulosa cells to
      express 3beta-HSD might be insufficient in cystic follicles and accordingly they
      fail to ovulate. The differences of frequencies of 3beta-HSD-positive cells in
      the granulosa and theca interna layers between cystic and atretic follicles may
      be one of the reasons why regression is delayed in cystic follicles.

PMID- 14967933
TI  - Effects of BSA and fetal bovine serum in culture medium on development of rat
      embryos.
AB  - Rat 1-cell embryos, recovered from naturally mated females, were cultured in a
      chemically defined medium (mR1ECM) or in mR1ECM supplemented with BSA (4 mg/ml;
      mR1ECM-BSA) or fetal bovine serum (FBS; 10%, v:v; mR1ECM-FBS) instead of
      polyvinylalcohol. There was no difference in percentages of embryos that
      developed to the 2-cell to blastocyst stages between mR1ECM and mR1ECM-BSA, but
      in mR1ECM-FBS, no development beyond the 2-cell stage was observed. When embryos
      were transferred to mR1ECM-FBS from mR1ECM after 24 to 64 h of culture,
      development of embryos to and beyond the 4-cell stage was inhibited. However,
      when transferred after 80 h of culture, more embryos developed to blastocysts and
      hatching or hatched blastocysts than in embryos cultured in mR1ECM. When 8-cell
      embryos and early morulae obtained after 72 and 80 h of culture in mR1ECM,
      respectively, were cultured in mR1ECM-FBS, a higher proportion of early morulae
      developed to the blastocyst stage than did 8-cell embryos. When morulae obtained
      after culture in mR1ECM or mR1ECM-BSA were transferred to recipient females,
      there was no difference in proportions of fetuses obtained. However, a higher
      proportion of blastocysts cultured in mR1ECM-FBS developed to fetuses compared
      with those obtained in mR1ECM. These results indicate that BSA has neither
      deleterious nor beneficial effects on development of rat 1-cell embryos. In
      contrast, FBS has deleterious effects on early cleavage of embryos but it
      promotes more rapid development of morulae to blastocysts, resulting in better
      quality blastocysts.

PMID- 14967934
TI  - Dynamics of betaig-h3 mRNA expression during pregnancy in the uterus and the
      placenta of the mouse: a possible regulatory factor for trophoblastic invasion.
AB  - Changes in the betaig-h3 gene expression levels in the uterus during different
      reproductive stages and those in the placenta on different days of gestation in
      the mouse were examined by Northern blot analysis. The levels of betaig-h3
      expression rose steeply from the baseline level at proestrus to the maximum at
      estrus and then declined rapidly from 1st day of diestrus onward. During
      pregnancy, high levels of betaig-h3 mRNA were detected in the uterus on Day 4 of
      gestation, when the trophoblastic invasion of the implanted blastocysts was very
      active. In the pseudopregnant uterus, the betaig-h3 expression levels exhibited
      the same patterns as those in the pregnant uterus, although the levels were much
      lower at all stages than those in the pregnant uterus. In the placenta, the
      betaig-h3 expression levels gradually increased from Day 7 onward and peaked on
      Day 18 of gestation. In situ hybridization analysis of the pregnant uterine
      tissues revealed that the luminal as well as the glandular epithelium expressed
      betaig-h3 mRNA at high levels. In the placenta, high levels of betaig-h3
      transcripts were detected in the decidual cells and the giant trophoblast cells.
      These findings suggest that betaig-h3 might play a role in regulating the
      invasiveness of trophoblast cells during implantation and placentation of
      hemochorial type when extensive trophoblastic invasion of the endometrium takes
      place.

PMID- 14967935
TI  - Origin of plasma insulin-like growth factor-I (IGF-I) during estrus in goats.
AB  - The objective of this study was to clarify the origin of the increase in plasma
      insulin-like growth factor-I (IGF-I) during estrus in goats. Focusing on the
      uterus, the effect of estradiol-17 beta (E2) on the secretion of IGF-I was
      examined using ovariectomized and hysterectomized animals. A single 5 microg/kg
      BW of E2 was injected intramuscularly into ovariectomized and hysterectomized
      goats for 3 consecutive days, and plasma IGF-I concentrations in the two groups
      were compared. The concentrations of IGF-I rose after the treatments in both
      groups. The concentrations were significantly higher from 3 to 8 days after the
      treatment than before the treatment in ovariectomized goats (P<0.05), and from 1
      to 3 days after the treatment than before in hysterectomized goats (P<0.05). Thus
      higher concentrations of plasma IGF-I tended to last longer in ovariectomized
      than hysterectomized goats. The area under the IGF-I response curve for the 8-day
      period after the first injection of E2 tended to be greater in ovariectomized
      than in hysterectomized goats. The results show that E2 increases plasma IGF-I
      concentrations in goats, and suggest that E2-stimulated IGF-I in plasma may
      originate mainly from the uterus.

PMID- 14967936
TI  - Factors affecting premature chromosome condensation of cumulus cell nuclei
      injected into rat oocytes.
AB  - To date, production of cloned rats by somatic cell nuclear transfer (NT) has not
      yet been successful. Inducing premature chromosome condensation (PCC) of injected
      cell nuclei in recipient cytoplasm is considered essential for successful mouse
      cloning by the Honolulu method. In the present study, some factors affecting PCC
      of rat cumulus cell nuclei injected into rat oocytes were examined. Wistar female
      rats (young: 4 to 5-week-old, mature: > or =10-week-old) were superovulated by
      injections of eCG and hCG, and oocytes recovered 14 or 17 h after hCG injection
      were received with cumulus cell nuclei using piezo-driven micromanipulator. When
      the oocytes were recovered 14 h post-hCG injection from young rats and the
      nuclear injection into oocytes was completed within 45 min, PCC was observed in
      44-49% of NT oocytes. In the case of oocytes from mature rats, PCC occurred in 11
      19% of the NT oocytes. Oocytes recovered 17 h post-hCG injection did not support
      PCC of the injected nuclei (0-7%) regardless of the donor age. Treatment of
      oocytes with a neutral cysteine protease inhibitor, N
      acetylleucylleucylnorleucinal, slightly increased the incidence of PCC (48 vs
      37%). Comparison of rat strains for oocyte donors indicated that proportions of
      NT oocytes undergoing PCC in Wistar and LEW oocytes (41-46%) were higher than
      those in Donryu and F344 oocytes (17-25%). Thus, ability of rat oocytes to
      promote PCC of the injected nuclei is dependent on the characteristics of
      oocytes, such as age or strain of donor rats, and timing of oocyte recovery.

PMID- 14967937
TI  - Trophinin is expressed in the porcine endometrium during the estrous cycle.
AB  - We investigated endometrial expression of trophinin mRNA and protein, homophilic
      cell adhesion molecules, during the estrous cycle of gilts. An immunopositive
      reaction for trophinin was observed in the luminal and glandular epithelia of the
      endometrium at all stages of the estrous cycle, but not in endometrial stromal
      cells or the myometrium. A partial coding sequence of porcine trophinin was
      similar to sequences in humans and mice, with homologies of 75% and 70%,
      respectively. As in humans and mice, the trophinin gene is expressed in the
      endometrium. Trophinin, however, is expressed in the endometrium of the pig
      throughout the estrous cycle, higher expression levels were observed at some
      points of the luteal phase, as in humans. These findings suggest that regulation
      of trophinin gene expression in the pig is different from that in mice, but
      similar to that in humans. Furthermore, the present results suggest that the pig
      might be a suitable model for studying the physiological importance of trophinin
      in early pregnancy in humans.

PMID- 14967938
TI  - Expression of nitric oxide synthase-3 in porcine oocytes obtained at different
      follicular development.
AB  - The present study was designed to determine the localization of nitric oxide
      synthase-3 (NOS-3) in porcine follicles during follicular development. A 130-kDa
      NOS-3 protein was found with greater frequency much in the oocytes than in the
      cumulus cells, as revealed by Western blotting analysis. The content of NOS-3 in
      the oocyte was higher in large follicles (> 7-mm diameter) than in small
      follicles (< 2-mm). The data by Western blotting showed the same pattern as the
      observations obtained from the immunohistochemical studies, in which the
      periphery of the oocyte stained strong positive. The inner surface cell layer of
      granulosa cells and cumulus cells were positive staining, especially in large
      antral follicles. In the primordial follicles, NOS-3 was restricted to the
      cytoplasm of oocytes, and no stained product was observed in the nucleus of
      oocytes or granulosa cells. A significant synthesis of NO by oocytes was observed
      in the presence of ionomycin, but not in the absence of ionomycin, indicating
      that oocyte NOS-3 functions in response to transient elevations in the
      intracellular calcium level. We concluded that NOS-3 is expressed in the oocyte
      from the primordial follicular stage to antral follicular stage, and that it is
      functional at least in the antral follicles.

PMID- 14967939
TI  - Oxytocin mediates some effects of insulin-like growth factor-I on porcine ovarian
      follicles.
AB  - The aims of the present study were (1) to investigate the influence of insulin
      like growth factor-I (IGF-I) on follicular size, on the secretion of oxytocin
      (OT), progesterone (P), estradiol (E), IGF binding protein-3 (IGFBP-3), inhibin
      A, inhibin B and cAMP and on the expression of proliferation-associated peptide
      PCNA, ERK-related mitogen activated protein kinase (MAPK/ERK1, 2) and protein
      kinase A (PKA) in cultured porcine ovarian follicles; (2) to examine the effects
      of OT on IGF-I and on these functions; and (3) to determine whether the effects
      of IGF-I can be mediated by OT. To define the involvement of OT in mediating IGF
      I action, we compared responses of porcine ovarian follicles to IGF-I and OT and
      examined whether blockade of endogenous OT by specific antiserum can affect IGF-I
      action. It was observed that IGF-I (1, 10 or 100 ng/ml) was able to prevent a
      decrease in the size of ovarian follicles during culture and caused an increase
      in the diameter of some follicles. It also stimulated the secretion of OT, P,
      IGFBP-3, inhibin A and cAMP, decreased the secretion of E and inhibin B
      (RIA/EIA/ELISA), and induced the expression of PCNA, PKA, MAPK/ERK1, but not
      MAPK/ERK2 (Western blotting). Like IGF-1, OT (100 ng/ml) prevented decrease in
      follicular size and increased the diameter of some follicles. It also stimulated
      the secretion of P and IGF-I, but not E. Antiserum against OT (1%), when given
      alone, did not affect the reduction of follicular size but slightly increased the
      percentage of follicles increasing their diameter during culture. The antiserum
      also inhibited secretion of OT and cAMP but not the secretion of P, E, IGFBP-3 or
      the expression of PKA, MAPK/ERK1 or 2. When given together with IGF-I, the
      antiserum prevented the stimulatory action of IGF-I on the proportion of enlarged
      follicles and on OT, IGFBP-3 and MAPK/ERK1. It augmented the effect of IGF-I on
      P, but not the effect on E, cAMP, PKA or MAPK/ERK2. These observations
      demonstrate the involvement of IGF-I and OT in the control of ovarian follicular
      size and follicular cell proliferation, progestagen, estrogen, IGFBP-3, inhibin A
      and B secretion and in cAMP/PKA- and MAPK/ERK1-dependent intracellular
      mechanisms. Furthermore, the reciprocal stimulation of IGF-I and OT and the
      similarity of some their effects, together with the prevention or augmentation of
      some IGF-I effects after OT blockade, suggest that IGF-I action can be mediated
      by OT.

PMID- 14967940
TI  - Glucoprivation-induced Fos expression in the hypothalamus and medulla oblongata
      in female rats.
AB  - Glucoprivation induced by 2-deoxy-D-glucose (2DG) suppresses pulsatile
      luteinizing hormone (LH) secretion in female rats. The suppression is enhanced in
      the presence of estrogen. In the present study, 2DG-induced Fos expression was
      examined in the solitary tract nucleus (NTS), hypothalamic paraventricular
      nucleus (PVN), raphe obscurus nucleus (ROb) and raphe pallidus nucleus (RPa),
      which have been previously suggested to be involved in glucoprivation-induced
      suppression of LH secretion in female rats. Ovariectomized (OVX) or estrogen
      primed ovariectomized (OVX+E(2)) rats were injected intravenously with 2DG (400
      mg/kg BW). The brain was removed 1 h after the injection. The number of Fos-like
      immunoreactive (Fos-li) cells in the PVN and NTS was significantly increased in
      OVX+E(2) rats compared with control groups, but did not show a significant
      increase in the OVX group. Few Fos-li cells were observed in the ROb and RPa in
      all groups. All of the Fos-li cells in the PVN and NTS were neurons because they
      had immunoreactivities to microtubule-associated protein 2. Some Fos-li cells
      (8.3%) had tyrosine hydroxylase-like immunoreactivities in the NTS in 2DG-treated
      OVX+E(2) rats. These results suggest that neurons in the PVN and NTS are involved
      in the estrogen-dependent neural cascade mediating glucoprivic suppression of LH
      secretion in female rats.

PMID- 14967941
TI  - Parthenogenetic activation and subsequent development of porcine oocytes
      activated by a combined electric pulse and butyrolactone I treatment.
AB  - This study was designed to evaluate the parthenogenetic activation of porcine
      oocytes matured in vitro for a varied period after combined electric pulse (EP;
      1500 V/cm, 100 microsec) and Butyrolactone I (BL I). After 36 h of maturation
      culture, the rates of activated oocytes and oocytes with two pronuclei were
      significantly lower than those of oocytes cultured for 42 and 48 h after EP.
      However, when treated by a combined EP and BL I (150 microM), these rates
      increased to the same level as 42 and 48 h oocytes. When oocytes cultured for 48
      h and activated by a combined EP and BL I treatment were subsequently cultured in
      mNCSU37 medium, the rates of embryos cleaved and developed to the blastocyst
      stage were significantly higher than those in Whitten's medium. In contrast, when
      activated oocytes were cultured in mNCSU37 medium under two oxygen environments
      (5% vs 20% O(2)), there was no difference in the rates of cleavage, blastocyst
      formation and nuclear numbers per blastocyst. Our results demonstrated that the
      combined EP and BL I treatment of porcine oocytes matured in vitro is capable of
      producing high rates of good quality blastocysts when cultured in a suitable in
      vitro condition.

PMID- 14967942
TI  - Predictive value of the area of expanded cumulus mass on development of porcine
      oocytes matured and fertilized in vitro.
AB  - The objective of the present study was to investigate the correlation between the
      degree of cumulus expansion and in vitro development of porcine cumulus-oocytes
      complexes (COCs) matured and fertilized in vitro. The COCs were matured in the
      maturation medium (IVMM) supplemented with 15% or 5% of porcine follicular fluid
      (PFF) from small, medium and large follicles (<2 mm, 2-5 mm and >5 mm,
      respectively). COCs cultured in IVMM with PFF for 48 h displayed less expansion
      than those cultured in IVMM alone (P<0.05), irrespective of follicle size. After
      culture for 24 h in IVMM with PFF and for another 24 h in IVMM alone, the degree
      of cumulus expansion was more prominent than culture in the presence of PFF for
      the entire 48 h period (P<0.05), but the percentages of oocytes with PB I showed
      no significant difference between the control and experimental groups (P>0.05).
      After in vitro fertilization, the oocytes failed to develop to the
      morula/blastocyst stages except for those matured in IVMM supplemented with 15%
      or 5% PFF obtained from >5 mm follicles for the first 24 h and followed by in
      IVMM alone for the second 24 h (12.5% and 11.1% of the embryos developed to
      morulae and blastocysts, respectively). The expanded cumulus areas of COCs were
      significantly positively correlated with their in vitro development (p=0.0058,
      0.0001 and 0.0348 for the percentages of embryos developed to 2-4 cell, beyond 4
      cell and morula and blastocyst stages, respectively). In conclusion, PFF had an
      inhibiting effect on cumulus expansion, and the inhibitory effect decreased
      progressively with the increase in size of follicles from which PFF was obtained,
      and the action of PFF on cumulus expansion was affected by the PFF culture time.
      The areas of the expanded cumulus mass may be used as a parameter to predict
      development of porcine oocytes matured and fertilized in vitro.

PMID- 14967943
TI  - Pfaffia paniculata-induced changes in plasma estradiol-17beta, progesterone and
      testosterone levels in mice.
AB  - The present study undertook chemical analysis of components of Pfaffia paniculata
      roots. In addition, an animal experiment was conducted in which mice had ad
      libitum access to water enriched with powdered P. paniculata root for 30 days.
      Changes in plasma concentrations of estradiol-17beta and progesterone in female
      mice and of testosterone in male mice were ascertained. The results revealed that
      P. paniculata roots contain two types of phytosteroids, beta-sitosterol and
      stigmasterol, in addition to other compounds such as pfaffic acid, allantoin,
      saponins, beta-sitosteryl-beta-D-glucoside, and stigmasteryl-beta-D-glucoside.
      Regarding changes in plasma concentrations of hormones, levels of the sex
      hormones estradiol-17beta, progesterone and testosterone were clearly higher for
      mice that drank P. paniculata root-enriched water than for mice that drank plain
      water. Powdered P. paniculata root is easily dissolved in feed or water, and as
      no adverse reactions were seen in mice within 30 days of oral intake, consumption
      of P. paniculata for long periods of time appears safe.

PMID- 14967944
TI  - Japanese Society for Animal Reproduction: award for outstanding research 2002.
      Mechanisms controlling neurohypophysial hormone release in the rat.
AB  - To explore mechanisms of osmotic control of neurohypophysial hormone release,
      electrical activity of magnocellular neurons (MCNs) in the hypothalamus, related
      neurons and efferent renal sympathetic nerve activity (RSNA) were recorded from
      urethane-anesthetized rats. Local osmotic stimulation applied to organum
      vasculosum of the lamina terminalis (OVLT) or median preoptic nucleus (MnPO)
      excited MCNs. Although OVLT neurons projected to MCNs were unresponsive to
      hyperosmotic stimulation, those projected to MnPO and also receiving excitatory
      inputs from MCNs, were excited by it. MnPO neurons, which were driven by OVLT
      stimulation and projected to MCNs, were also osmosensitive. Excitatory
      connections thus exist from MCNs to OVLT, from OVLT to MnPO and from MnPO to
      MCNs. Neurons in each of these connections were osmosensitive. This circuit thus
      appears to constitute an osmoreceptor complex essential for the osmoreception of
      MCNs. MnPO neurons constituting a part of the osmosensitive circuit were also
      sensitive to hemodynamic change. Thus this circuit may integrate hemodynamic and
      osmotic information. Local anesthesia of MnPO diminished activation of RSNA and
      pressor response induced by third cerebroventricular injection of hypertonic
      saline. The results suggest that the osmosensitive circuit is involved in body
      fluid regulation not only by controlling vasopressin secretion but also by
      modulating sympathetic outflow.

PMID- 14967945
TI  - Japanese Society for Animal Reproduction: award for outstanding research 2002.
      Cryopreservation of follicular oocytes and preimplantation embryos in cattle and
      horses.
AB  - Factors affecting sensitivity of preimplantation embryos and follicular oocytes
      to cryopreservation were analyzed in the equine and bovine species. (1) Survival
      of equine blastocysts after two-step freezing in the presence of glycerol as the
      cryoprotective agent (CPA) was influenced by development of the embryonic
      capsule. The use of ethylene glycol (EG) with sucrose as CPAs improved the post
      thaw survival of blastocysts and made it possible to transfer the embryos into
      recipient mares without removing the CPAs. In addition, early blastocysts
      cryopreserved by vitrification could develop both in vitro and in vivo when the
      embryos were exposed to vitrification solution in a stepwise manner. The
      vitrification procedure was also applied to the relatively large expanded
      blastocysts. (2) Bovine embryos produced in vitro have been considered to be
      highly sensitive to the process of cryopreservation. To solve this problem, Day-7
      blastocysts produced in a serum-free system were cooled at 0.3 C/min rather than
      0.6 C/min before being plunged into liquid nitrogen, resulting in no loss of the
      post-thaw viability. The supplementation of LAA in IVM/IVF media or IVC medium
      was effective in producing pronuclear-stage zygotes or morula-stage embryos
      relatively tolerable to freezing, respectively. (3) Transmission electron
      microscopic observation of immature equine oocytes showed that cellular injury
      occurred near the sites of gap-junctions between cumulus cells and the oocyte. In
      cattle, higher fertilization rates of oocytes were obtained when the oocytes were
      subjected to cryopreservation at an intermediate stage during IVM (GVBD for
      freezing, Met-I for vitrification). Vitrification of bovine Met-II oocytes in
      open-pulled glass capillaries, characterized by an ultra-rapid cooling rate
      (3,000-5,000 C/min), was found to avoid any harmful influence of vitrification
      and warming.

PMID- 14967946
TI  - Japanese Society for Animal Reproduction: award for outstanding research 2002.
      The development and prevalence of the transfer technique for frozen-thawed
      embryos of Japanese black beef cattle in Tochigi Prefecture.
AB  - The conditions of embryo transfer by the stepwise method, in which frozen-thawed
      embryos are transferred on day 7 (day 0=onset of estrus), were investigated with
      the aim of increasing pregnancy rates in frozen-thawed embryo transfer. The use
      of a vaginal speculum to prevent bacterial infection when passing an embryo
      transfer gun through the vagina yielded a pregnancy rate equal to or higher than
      that with application of a sheath cover to the transfer gun. Administration of a
      sedative, xylazine, to recipient cattle for preventing movement at the time of
      embryo transfer improved the pregnancy rate. The influence of the time from
      thawing of frozen embryos to transfer and of the transportation of the recipient
      by truck upon pregnancy rate was investigated. Embryo transfer within 60 minutes
      after aspiration into a straw or transportation of the bovine recipient, 1.5
      hours each way before and after transfer, had no influence on pregnancy rate.
      Relations of the embryonic developmental stage and morphological quality after
      thawing of frozen embryos to pregnancy rate were investigated in recipients of
      nulliparous Holstein heifers. The pregnancy rate increased as the embryonic
      developmental stage advanced from compacted morula, early blastocyst, and
      blastocyst in that order. The pregnancy rate obtained with blastocyst stage
      embryos was significantly (P<0.05) higher than that with compacted morula stage
      embryos, and there was no significant difference in pregnancy rates between
      excellent morphological quality and good morphological quality for compacted
      morula stage embryos. When correlation of luteal function and pregnancy rate was
      investigated in bovine recipients, pregnancy rate showed a tendency to increase
      with increasing blood progesterone (P) concentration on the day before (on day 6
      after estrus) and the day of embryo transfer. The pregnancy rate in bovine
      recipients, which showed a blood P concentration of > or =2.5 ng/ml on the day
      before embryo transfer, was significantly (P<0.05) higher than that in those with
      a blood P concentration of <2.5 ng/ml. Pregnancy rate showed a tendency to
      increase with decreasing blood estradiol-17beta (E2) concentration on the day of
      embryo transfer. Activation of luteal function by administration of human
      chorionic gonadotropin (hCG) in cycling cattle was investigated for its effect on
      increasing pregnancy rate in bovine recipients. A follicle coexisting with cyclic
      CL ovulated and induced CL formed after injection of hCG 1,500 IU 5 days after
      ovulation. The blood P concentration was significantly (P<0.05) higher in the
      administration group than in the control group, and the blood E2 concentration
      rapidly decreased, showing a lower concentration than in the control group. These
      results suggest the possibility that the pregnancy rate could be improved by
      administration of hCG. Pregnancy rate following intramuscular injection hCG 1,500
      IU was comparatively investigated in parous Japanese Black beef cattle receiving
      frozen-thawed embryos 7 days after estrus. Pregnancy rate was 67.5% in the group
      in which hCG was administered on day 6 after estrus, and was significantly
      (P<0.05) higher than that in the control group (45.0%) and the group in which hCG
      was administered on day 1 after estrus (42.5%), revealing that hCG administration
      facilitated pregnancy. Transfer of frozen-thawed embryos in the blastocyst stage
      within 60 minutes after the aspiration into a straw, with a vaginal speculum
      after administration of xylazine is suggested as a way of improving pregnancy
      rate in bovine recipients with favorable luteal function and in those with luteal
      function activated by administration of hCG on the day before embryo transfer.

PMID- 14967947
TI  - Effect of activation methods for bovine oocytes after intracytoplasmic injection.
AB  - A principal nuclear transfer procedure is to inject a donor cell into the
      perivitelline space in an enucleated oocyte and then electric fusion is performed
      (cell fusion method). The effects of activation methods in reconstructed oocytes
      for the serum-starved somatic cell cloning procedure were investigated in this
      study by means of intracytoplasmic injection (i.c.i.). Bovine oocytes were
      enucleated at 18-22 h for in vitro maturation, and subsequently the nucleus of
      cumulus cell collected from Japanese Black Bulls (JBCC) after 5-7 days of starved
      culture was injected into the recipient cytoplast with a piezo-micromanipulator.
      At 1 h after i.c.i., reconstructed oocytes were stimulated with ethanol (ET) or
      calcium ionophore (CaI) as the first activation treatment, followed by
      cycloheximide (CHX) or 6-dimethylaminopurin (DMAP) treatment as the second
      activation. In the experiment on the first activation method, the proportion of
      reconstructed oocytes developing to the blastocyst stage was significantly
      (p<0.01) higher in the ET activation method than that with CaI (10.5% and 4.7%,
      respectively). And the experiment on the second activation method after ET
      treatment showed similar proportions of blastocyst development in both CHX and
      DMAP treatments (5.9% and 2.8%, respectively). The present results indicated that
      combined activation treatment with ET and CHX was efficient for reconstructed
      bovine oocytes by i.c.i.

PMID- 14967948
TI  - Matrix-metalloproteinases-2 and -9 production in bovine endometrial cell culture.
AB  - In vitro cell culture is a convenient tool for studying cellular mechanisms. In
      the present study, production of matrix-metalloproteinases (MMPs) in bovine
      endometrial (containing both epithelial and stromal cells) monolayer cells was
      examined. Blastocysts attached to the endometrial cells in a monolayer culture
      were examined for their effects on MMP-2 production. Initial attachment of
      blastocysts to the monolayer inhibited MMP-2 production by endometrial cells. But
      once trophoblast cells began to migrate into the endometrial cell layer, MMP-2
      production increased, and at the same time MMP-9 production also became evident
      in the medium. In order to understand how blastocysts affected MMP-2 production,
      we examined the effect of progesterone, estradiol, insulin-like growth factors
      (IGFs), tumor necrosis factors (TNFs), and interferon-tau (IFN-tau)
      supplementation. It was IFN-tau that inhibited the production of MMP-2. In
      addition, progesterone at a lower dose appeared to inhibit MMP-2 production. Both
      TNF-alpha and TNF-beta strongly stimulated the production of MMP-2 and MMP-9,
      whereas IGFs had no effect. Based on these findings, it appears that conceptus
      has the capacity to inhibit MMP activity.

PMID- 14967949
TI  - Estrogen receptor alpha expression in the medial preoptic area and the medial
      basal hypothalamus under different physiological conditions in cattle.
AB  - The distribution and morphology of immunoreactive estrogen receptor alpha
      (ERalpha)- containing cells were examined in the cattle brain. The brains were
      collected from two cows and a male calf. One of the cows was sacrificed one week
      after parturition. ERalpha expressions in the preoptic area of the rostral
      forebrain and the medial basal hypothalamic area were evaluated
      immunohistochemically using a mouse monoclonal antibody. In all animals, the
      signals that indicate ERalpha were detected in the medial preoptic area, the
      level of the organum vasculosum of the lamina terminalis and the bed nucleus of
      the stria terminalis. In the caudal hypothalamic region, they were detected in
      the arcuate nucleus, the periventricular and ventromedial hypothalamic nuclei.
      ERalpha-containing cells were characterized by a dense nuclear reaction product.
      In all the subjects examined, ERalpha signals were clearly detected in the
      cytoplasm as well. The density of ERalpha expression was different among the
      three cattle; the number of ERalpha containing cells in the postpartum cow was
      much lower than that in the other cow and the male calf. The present findings
      suggest that ERalpha expression in the forebrain is influenced by the
      reproductive status in the cattle.

PMID- 14967950
TI  - Oocyte transport: Developmental competence of bovine oocytes arrested at germinal
      vesicle stage by cycloheximide under air.
AB  - The effects of the medium (TCM 199 or SOFaa) and temperature (20 or 39 C) during
      meiotic arrest by cycloheximide (CHX) under air on the developmental competence
      of bovine oocytes after in vitro maturation (IVM) and fertilization (IVF) were
      investigated. Oocytes were maintained in meiotic arrest by 10 microg/ml CHX in a
      50-microl droplet of 25-mM HEPES-buffered TCM 199 (H199) at 39 C or synthetic
      oviduct fluid (HSOFaa) at 20 or 39 C in air for 24 h. After release from the
      arrest, the oocytes was matured and fertilized in vitro and their developmental
      competence was examined. The developmental rate of oocytes arrested in HSOFaa at
      20 C to the blastocyst stage was similar to that of non-arrested oocytes but was
      significantly higher (P<0.05) than that of oocytes arrested at 39 C in H199 or in
      HSOFaa. In consideration of oocyte transport conditions, we also investigated the
      meiotic arrest of oocytes maintained in a 0.25-ml straw by CHX individually with
      10 microl HSOFaa or as a group (40-50 oocytes) with 170-200 microl HSOFaa at 20 C
      in air for 24 h. After release from meiotic arrest, the developmental competence
      of these oocytes was assessed similarly. The developmental rate of oocytes
      treated with CHX individually was similar to that of those treated with CHX in 50
      microl droplet of HSOFaa at 20 C. However, the developmental rate of oocytes
      treated with CHX as a group was lower than that of oocytes treated with CHX in a
      50-microl droplet. Five blastocysts developed from oocytes maintained in meiotic
      arrest in a plastic straw were transferred to five recipient heifers.
      Consequently, three recipients became pregnant and 2 calves were delivered. The
      results of the present study indicate that bovine oocytes treated with CHX in
      HSOFaa at 20 C under air retain the same developmental competence as non-arrested
      oocytes.

PMID- 14967951
TI  - Distribution of glutamic acid decarboxylase, neurotensin, enkephalin,
      neuropeptide Y, and cholecystokinin neurons in the septo-preoptic region of male
      rats.
AB  - Neurons in the lateral septum (LS) and preoptic area (POA) are known to play an
      inhibitory role in feminine sexual behavior regulation in male rats. In this
      study, the distribution of neurons containing glutamic acid decarboxylase (GAD)
      and of the peptidergic neurotransmitters neurotensin (NT), enkephalin (ENK),
      neuropeptide Y (NPY), and cholecystokinin (CCK), was examined
      immunohistochemically in the LS and POA of castrated male rats subcutaneously
      implanted with estrogen-containing Silastic tubes. Colchicine was injected into
      the lateral ventricle of the animals. The forebrain sections were immunostained
      for each substance. A large number of GAD-immunoreactive (ir) cells were found in
      the LS. Many NT-ir cells were seen in the intermediate and ventral parts of the
      LS at the rostral and middle levels. A considerable number of ENK-ir cells were
      scattered over the LS at the rostral and middle levels and were observed in the
      ventral part of the caudal LS. There were only a few NPY-ir cells in the LS. No
      CCK-ir cells were observed in the LS. In the POA, GAD-ir cells were observed in
      abundance. Many NT-ir cells were seen, especially in the medial preoptic nucleus.
      Some ENK-ir cells and a few NPY-ir cells were found in the medial POA. CCK-ir
      cells of the POA were restricted to the periventricular and paraventricular
      hypothalamic nuclei.

PMID- 14967952
TI  - Cloning and chromosomal localization of mouse 20alpha-hydroxysteroid
      dehydrogenase gene.
AB  - 20alpha-hydroxysteroid dehydrogenase (20alpha-HSD), a member of the aldo-keto
      reductase (AKR) superfamily, metabolizes progesterone to its inactive form,
      20alpha-dihydroprogesterone (20alpha-OHP). 20alpha-HSD is associated with
      functional luteolysis and plays a significant role in the reproductive system of
      rodents. Here we report cloning and determination of the chromosomal location of
      the mouse 20alpha-HSD gene. The mouse 20alpha-HSD gene cloned using 129 SvJ mouse
      genomic library spanned approximately 18 kb from exon 1 to exon 9. A single
      transcription start site was identified by 5'-rapid amplification of cDNA ends
      (RACE) at the site of 50 nucleotides upstream from the ATG translation initiation
      codon. The exon-intron organization of mouse and human 20alpha-HSD genes were
      similar. Using 17.5 kb of genomic clone as a probe, we determined the chromosomal
      location by fluorescence in situ hybridization (FISH). The chromosome in which
      the mouse 20alpha-HSD gene was detected was identified as chromosome (Chr) 13
      according to simultaneous G- and R-banding. Because type 5 17beta-HSD gene, a
      member of the AKR superfamily, is also located on Chr 13, the present result
      supports the syntenic relationship between mouse Chr 13 and human Chr 10, which
      was previously suggested at the chromosomal loci of a gene cluster of the AKR
      superfamily.

PMID- 14967953
TI  - Inhibin secretion in the golden hamster (Mesocricetus auratus) testis during
      active and inactive states of spermatogenesis induced by the restriction of
      photoperiod.
AB  - Gonadal function in the male golden hamster (Mesocricetus auratus) was
      investigated during exposure to a short photoperiod condition. Within 3 weeks of
      exposure to the short photoperiod condition, FSH and testosterone in the plasma
      significantly decreased, and subsequently immunoreactive (ir)-inhibin
      significantly decreased. Testicular contents of ir-inhibin and testosterone, and
      pituitary contents of LH and FSH also significantly decreased by 3 weeks with
      regression of weight of testes, epididymis and seminal vesicles and sperm head
      count. Circulating LH varied but not significantly. Thereafter, all reproductive
      parameters and secretion of LH, FSH, ir-inhibin and testosterone gradually
      recovered after 17 weeks of exposure even though animals continued to be
      subjected to the short photoperiod condition. Plasma concentrations of inhibin B
      and inhibin pro-alphaC were detectable and were significantly decreased after 15
      weeks of exposure to the short photoperiod, but their levels were still
      detectable. Immunopositive reaction of inhibin alpha and betaB subunits was found
      in Sertoli cells and Leydig cells in the regressed testes of animals subjected to
      short photoperiod as was also seen in animals before exposure to the short
      photoperiod. Although the spermatogenic cycle was suppressed like prepubertal
      animals, the present study showed that the testicular recovery, so-called
      refractoriness, is functionally different from the developing stage of immature
      animals, especially with regard to inhibin secretion. The present results showed
      that changes in FSH preceded changes in inhibin during the regression and
      recovery phases, indicating that FSH is a major regulatory factor of inhibin
      secretion in male golden hamsters. The present study also demonstrated that
      regressed testes still secrete a small amount of bioactive inhibin during
      exposure to a short-photoperiod condition.

PMID- 14967954
TI  - Role of tyrosine kinase- and MAP kinase-dependent intracellular mechanisms in
      control of ovarian functions in the domestic fowl (Gallus domesticus) and in
      mediating effects of IGF-II.
AB  - The aim of our study was to examine the involvement of IGF-II, tyrosine kinases
      (TK)- and MAP kinases (MAPK)-dependent intracellular mechanisms in the control of
      ovarian functions in the domestic fowl, as well as the role of these kinases in
      mediating the IGF-II effect on this process. For this purpose, we studied the
      influence of IGF-II (0,1,10 or 100 ng/ml), inhibitors of TK (AG1024, 1
      microg/ml), MAPK (PD98059, 5 microg/ml), and their combinations, on proliferation
      (expression of proliferation-related substances PCNA), apoptosis (apoptosis
      associated protein bax), TK (phosphotyrosine), MAPK (ERK1,2), cyclin-dependent
      protein kinase 2 (p34/cdc2) and transcription factor CREB-1, as well as on the
      release of progesterone (P), testosterone (T), estradiol (E) and arginine
      vasotocin (AVT) in cultured fragments of ovarian follicles. The presence of
      substances within ovarian cells was evaluated by SDS PAGE-Western immunoblotting,
      and release of the substances was measured by using RIA/EIA of ovarian fragments
      conditioned medium. It was found, that the addition of IGF-II to the culture
      medium (1-100 ng/ml) substantially increased expression of PCNA, MAPK and CREB,
      and decreased the level of p34/cdc2 and bax, but not TK. Furthermore, exogenous
      IGF-II inhibited P (at a concentration of 100 ng IGF-II/ml medium), and
      stimulated T (1,10,100 ng/ml), E (10,100 ng/ml) and AVT (1 ng/ml) release by
      cultured ovarian cells. Inhibitor of TK, when given alone, increased MAPK and E,
      inhibited p34/cdc2 and AVT, and did not affect accumulation of TK, P or T.
      Furthermore, TK blocker prevented effects of IGF-II on T, E and AVT, but not on
      TK, MAPK, p34/cdc2 and P. MAPK blocker augmented PCNA, MAPK, T and AVT
      expression, but not P or E, and suppressed expression of p34/cdc2 and bax.
      Furthermore, MAPK inhibitor, given together with IGF-II, prevented or even
      reversed the action of IGF-II on PCNA, P, T and AVT, but not on MAPK, p34/cdc2,
      CREB, bax or E. These observations suggest the involvement of IGF-II, TK and MAPK
      in the control of proliferation, apoptosis, steroid and peptide hormones by avian
      ovarian cells, as well as of the involvement of these kinases in mediation of
      some IGF-II effects on ovarian cells.

PMID- 14967955
TI  - Expression of a testis-specific form of TBP-related factor 2 (TRF2) mRNA during
      mouse spermatogenesis.
AB  - The gene encoding TATA-binding protein-related factor 2 (TRF2/TLF/TLP/TRP),
      essential for the progress of spermiogenesis, is abundantly expressed in
      mammalian testis. A sequence database search revealed that mouse TRF2 is encoded
      by two mRNAs containing the same protein-coding region and different 5'
      untranslated regions. Northern blot analysis using DNA probes specific for the 5'
      untranslated regions demonstrated that these two mRNAs are distinguished from
      each other by the expression patterns: ubiquitous and testis-specific expression.
      The ubiquitously expressed form of TRF2 mRNA was present at a very low level
      throughout testicular development, whereas expression of the testis-specific form
      was first detectable in the 14-day-old testis, and the mRNA level abundantly
      increased at the later stages of testicular development. Western blot analysis
      indicated that the TRF2 level increases during testicular development, which is
      consistent with the expression pattern of the testicular form of TRF2 mRNA. Thus,
      the presence of the testis-specific form of TRF2 mRNA may account for
      overexpression of the TRF2 gene in the testis.

PMID- 14967956
TI  - Nutritionally induced body weight loss and ovarian quiescence in Shiba goats.
AB  - Four female Shiba goats were used to determine the influence of body weight loss
      by dietary restriction on estrous cyclicity. The dietary restriction was started
      on the day following ovulation. The goats were fed hay cube and straw at an
      amount of 30% of energy requirement based on weekly body weight measurement. The
      ovaries were monitored daily by transrectal ultrasonography and blood samples
      were collected daily by jugular venipuncture for ovarian steroids analysis. After
      the start of food restriction, all animals lost body weight and entered ovarian
      quiescence. Intervals to the onset of ovarian quiescence tended to depend on the
      body weight of each animal at the start of food restriction. The mean
      concentration of progesterone during the mid-luteal phase (from 7 to 13 days
      after ovulation) in the last estrous cycle before ovarian quiescence was
      significantly lower than that in normal estrous cycle of the control period (19.7
      +/- 2.8 vs 12.3 +/- 2.2 ng/ml, P<0.05), whereas there was no significant
      difference in the length of the luteal phase, determined as the period when
      corpora lutea existed and concentrations of progesterone were equal to or greater
      than 1 ng/ml (15.8 +/- 1.5 vs 15.0 +/- 2.8 days, P>0.1). A rise of estradiol
      concentration and follicular growth in the follicular phase following a decline
      of progesterone level after luteal regression tended to be suppressed at the
      onset of ovarian quiescence. It seems that the present results are consistent
      with previous findings that nutritionally induced body weight loss influences the
      secretion of ovarian steroids and eventually induces ovarian quiescence.

PMID- 14967957
TI  - Metastatic gastrointestinal stromal tumor with an exon 11 c-kit mutation
      responding to the tyrosine kinase inhibitor imatinib.

PMID- 14967958
TI  - Downstaging of an advanced gastrointestinal stromal tumor by neoadjuvant
      imatinib.

PMID- 14967959
TI  - Brugada syndrome--an under-recognized electrical disease in patients with sudden
      cardiac death.
AB  - In 1992, Brugada and Brugada described 8 patients with a history of aborted
      sudden death and a distinct ECG pattern of right bundle-branch block with ST
      segment elevation in leads V1-V3 and normal QT interval in the absence of any
      structural heart disease. It is called Brugada syndrome now and is believed to be
      responsible for 4-12% of all sudden deaths and around 20% of deaths in patients
      with structurally normal hearts. Although this syndrome is observed worldwide and
      the exact prevalence is unknown, it is more common in the Southeast Asian
      countries. Repeated syncope, ventricular fibrillation, and sudden cardiac death
      have been reported in patients with Brugada syndrome. The clinical presentation
      of Brugada syndrome is distinguished by a male predominance and the appearance of
      arrhythmic events at an average age of 40 years. The Brugada syndrome is
      inherited in an autosomal dominant manner with incomplete penetrance and an
      incidence ranging between 5 and 66 per 10,000. The surface ECG manifestations of
      the syndrome can transiently disappear, but can be unmasked by potent sodium
      channel blockers in some cases. Mutations of the cardiac sodium channel SCN5A
      have been detectable in <20% of patients with Brugada syndrome. Recent genetic
      studies have confirmed the genetic heterogeneity of the disorder. Antiarrhythmic
      drugs appear to be of little use in prolonging survival and in preventing
      recurrences of ventricular arrhythmias. To date, implantable cardioverter
      defibrillator remains the best therapy to prevent sudden death in these patients.

PMID- 14967960
TI  - Application of tissue Doppler imaging in cardiology.
AB  - Tissue Doppler imaging (TDI) is a new echocardiographic technique employing the
      Doppler principle to measure the velocity of myocardial segments and other
      cardiac structures. It is well suited for the measurement of long-axis
      ventricular function. Impairment of longitudinal myocardial fiber motion is a
      sensitive marker of early myocardial dysfunction and ischaemia, and TDI might
      therefore become an important tool in routine echocardiography. The technique
      allows truly quantitative measurement of regional myocardial function both at
      rest and during stress echocardiography. TDI has great potential in the diagnosis
      of diastolic left ventricular dysfunction, overcoming the load-dependence of
      conventional Doppler techniques. Right ventricular function, intracardiac and
      pulmonary artery pressures, transplant rejection and intraventricular
      dyssynchrony can also be assessed. This article reviews the current and evolving
      applications of TDI in cardiology.

PMID- 14967961
TI  - Which features of the metabolic syndrome predict the prevalence and clinical
      outcomes of angiographic coronary artery disease?
AB  - BACKGROUND: The prevalence of the metabolic syndrome (MS) is growing. The Adult
      Treatment Panel (ATP) III provided a uniform definition of MS but no information
      on its predictive ability. METHODS: We tested the ability of MS and its
      components to predict angiographic coronary artery disease (CAD) and incident
      death/myocardial infarction (D/MI) over 2.8 +/- 2.3 years in a large cohort of
      patients undergoing angiography. ATP-III criteria were used for fasting glucose
      (FG), triglyceride (TG), high-density lipoprotein cholesterol (HDL), and blood
      pressure (BP); body mass index (BMI) >27 kg/m(2) was used as a surrogate for
      waist circumference. RESULTS: 3,128 subjects were studied; 65% had advanced CAD
      (>/=70% stenosis), and 35%, no CAD. MS was present in 64% (high FG 40%; high TG
      52%; low HDL 71%; high BP 76%; high BMI 58%). Presence of CAD was predicted by MS
      [adjusted odds ratio (OR) = 1.30, 95% CI 1.10-1.55, p = 0.003] and, individually,
      by high FG (OR = 1.90, CI 1.63-2.23) and low HDL (OR = 1.38, CI 1.18-1.62). In
      multivariable modeling, CAD was predicted by high FG (OR = 1.80, CI 1.51-2.16)
      and low HDL (OR = 1.57, CI 1.31-1.89) as well as by age, gender, family history,
      smoking, and LDL cholesterol (all p < 0.001). For secondary risk of incident
      D/MI, only high FG of MS features was predictive (adjusted hazard ratio 1.46, CI
      1.17-1.82, p = 0.001), and this risk was carried by diabetes (adjusted hazard
      ratio 1.71, p < 0.001); other predictors were age, heart failure,
      revascularization strategy, renal insufficiency, prior MI, and number of diseased
      vessels. CONCLUSION: MS has primary predictive ability for CAD, carried primarily
      by high FG and low HDL. Secondary predictive ability of MS features for clinical
      outcomes, in the setting of established CAD, is carried by diabetes alone.
      Dysglycemia deserves specific attention as a target for prevention and treatment.

PMID- 14967962
TI  - Off-pump coronary artery bypass grafting for patients with left main disease.
AB  - BACKGROUND: Multivessel off-pump coronary artery bypass grafting (CABG) has been
      performed with favorable results in our institute. In this study, we analyzed the
      outcomes in patients who underwent off-pump CABG for left main disease, since the
      surgical outcomes for such patients have not been clarified. METHODS: Between
      March 1, 1999 and July 30, 2002, a total of 147 patients with left main disease
      (112 males and 35 females, mean age 66.9 +/- 9.8 years) underwent off-pump CABG.
      Perioperative and follow-up data were entered into a structured database and the
      results were analyzed. RESULTS: Urgent or emergent surgery was performed in 25
      patients (17.0%), and a preoperative intra-aortic balloon pump was used in 12
      patients (8.2%). The mean number of bypass grafts was 3.2 +/- 1.0, and complete
      revascularization was performed in 127 patients (86.4%). There were 4 incidences
      of intraoperative conversion from off-pump to on-pump surgery. The mean
      intubation period, intensive care unit stay and postoperative hospital stay were
      9.4 +/- 13.0 h, 2.3 +/- 1.4 days and 13.4 +/- 7.3 days, respectively. There was 1
      hospital death (0.7%). Postoperative myocardial infarction was observed in 2
      patients (1.4%), postoperative stroke in 1 (0.7%), prolonged ventilator support
      in 5 (3.4%) and mediastinitis in 3 (2.0%). During the follow-up period of 2.1 +/-
      1.0 years, there were 4 deaths and 7 cardiac events. The actuarial 3-year
      survival rate was 97.0%, and the event-free rate was 94.3%. CONCLUSION: Our
      observations support off-pump CABG as a surgical option with a favorable outcome
      for patients with left main disease.

PMID- 14967963
TI  - The electrical T-axis and the spatial QRS-T angle are independent predictors of
      long-term mortality in patients admitted with acute ischemic chest pain.
AB  - OBJECTIVE: To investigate whether the orientation of the electrical T-axis and
      the spatial QRS-T angle provide independent diagnostic and prognostic information
      in patients presenting with acute chest pain. METHODS: Patients with symptoms
      suggestive of acute cardiac pathology, who were seen by a general practitioner
      and for whom a prehospital electrocardiogram (ECG) was recorded by the ambulance
      service between 1992 and 1994 were investigated. The ECGs (n = 2,261) for our
      study population were stored for off-line analysis by the Modular ECG Analysis
      System. QRS- and T-axes were computed from the reconstructed vectorcardiographic
      X, Y and Z leads. During the year 2000, a follow-up of the entire cohort was
      performed, and the vital status of the patients was determined via the civil
      registrar's office. Cox multivariable regression analyses were performed to
      evaluate the relation between the orientation of the T-axis, the spatial QRS-T
      angle and long-term mortality. RESULTS: An abnormal orientation of the T-axis and
      the spatial QRS-T angle were associated with an increased likelihood of cardiac
      diseases and an increased risk of all-cause mortality during short- and long-term
      follow-up. CONCLUSIONS: We conclude that the frontal T-axis and the spatial QRS-T
      angle are important determinants of diagnosis and prognosis in patients
      presenting with acute chest pain. The reintroduction of vectorcardiography in
      routine clinical practice might therefore be reconsidered.

PMID- 14967964
TI  - Formation of two aneurysms from a coronary artery-pulmonary artery fistula.

PMID- 14967966
TI  - [Toxoplasmosis in pregnancy: recent acquisitions and new prospects].
AB  - Congenital toxoplasmosis may develop after maternal primary infection during
      pregnancy. The infection is usually asymptomatic in pregnant women but poses a
      risk of severe effects on the fetus. In Italy the incidence is about 6 per
      thousand. The infection is transmitted to the fetus in approximately 50 percent
      of such cases. The risk of transmission rises with growing gestational age at the
      time of primary infection; on the contrary, the seriousness of the effect on the
      fetuses becomes less active with more advanced pregnancies. Infants with
      congenital toxoplasmosis are mostly asymptomatic at birth but long-term studies
      have indicated that up to 85% of them will develop serious sequelae as severe
      impairment of vision, mental retardation and deafness during the months or the
      years after the birth. Preventing congenital toxoplasmosis is fundamental. All
      seronegative women should be encouraged to observe good dietary and general
      health regulations until delivery. Today the diagnosis in the mother is more
      reliable because of the improvements in serological techniques. Moreover, it is
      possible to identify infected fetuses by prenatal procedures such as
      ultrasonography, amniocentesis and cordocentesis, of which the last two consent
      to detect the parasite and/or specific antibodies. Recently a polymerase chain
      reaction (PCR) assay has been developed for the detection of Toxoplasma in the
      amniotic fluid. Adequate serological screening of pregnant and prenatal diagnosis
      can be helpful in reducing the incidence of congenital toxoplasmosis; furthermore
      abortion should be reserved only to cases with severe toxoplasmosis revealed by
      ultrasonography. Early recognition of pregnant infection and a specific treatment
      could reduce the parasitic colonization in the placenta by more than 60% and
      prevent infection in the fetus. If the fetal infection has already occurred,
      maternal treatment may modify the fetal disease. Spiramycin as immediate
      treatment of maternal primary infection is essential in preventing Toxoplasma
      transmission to the fetus. If the fetus results non-infected, spiramycin should
      be prolonged until delivery. If the fetus is infected, pyrimethamine
      sulphadiazine combination should be given in repeated courses alternated with
      courses of spiramycin. However, there is an urgent need for more active and safer
      compounds; it would be useful to evaluate in the pregnant woman other potential
      therapeutic agents as atovaquone and azithromycin.

PMID- 14967965
TI  - Different type and localization of CD44 on surface membrane of regenerative renal
      tubular epithelial cells in vivo.
AB  - BACKGROUND: CD44 is a transmembrane glycoprotein comprising an extracellular
      domain, a transmembrane domain, and a cytoplasmic tail. Previous studies
      demonstrated that CD44 was generally restricted to lateral-basal plasma membrane
      (PM) of epithelial cells, whether it localized on apical PM in vivo has not been
      clarified. METHODS: In this study, we used a gentamicin-induced acute tubular
      necrosis (ATN) and spontaneous recovery model in rats and two distinct
      antibodies, an anti-rat distal extracellular domain (OX49) of standard CD44 (CD44
      OX49) and an anti-rat CD44 cytoplasmic tail (CD44CPT), to survey the localization
      of CD44-OX49 and CD44CPT on the PM in renal tubular epithelial cells in different
      recovery stages after ATN with immunohistochemistry and immunoelectron
      microscopic examinations. RESULTS: CD44-OX49 was localized not only on the
      lateral-basal PM in tubular epithelial cells, but also on the apical surface
      membrane in PCNA-positive newly regenerative tubular epithelial cells in early
      recovery stages after ATN. However, CD44CPT was only localized on the lateral
      basal PM. The immunoelectron-microscopic results showed that CD44-OX49
      localization was changed from the apical to lateral to basal surface membrane in
      renal tubular epithelial cells during the recovery process after ATN, finally
      disappearing from basal PM when normal polarized epithelial cells formed.
      CONCLUSIONS: These results suggest that there were two types of CD44 including
      CD44 without a cytoplasmic tail localizing on the apical surface membrane related
      to newly regenerative epithelial cells, and CD44 with a cytoplasmic tail
      localizing on the lateral-basal PM related to establishment of tubular epithelial
      cell polarity after ATN in vivo.

PMID- 14967967
TI  - [Gram positive microorganisms in urinary tract infections: epidemiology and
      therapy].
AB  - Urinary tract infections are the most frequent hospital acquired infections and
      represent one of the major problem in general practice. The predominant causative
      agents are enteric gram-negative bacteria. Nevertheless, the importance of gram
      positive bacteria, particularly Staphylococcus aureus and Enterococcus, has
      progressively increased especially in nosocomial urinary tract infections. Such
      an increase is probably related to the indiscriminate use of beta-lactam
      antibiotics or to the growing number of susceptible patients (surgical
      procedures, immunodeficiency, ecc.) The therapeutic approach of community and
      hospital infections is different: while in the first case treatment is usually
      not difficult, the therapy for nosocomial urinary tract infections should be
      based on the results of antibiotic susceptibility tests since a multiantibiotic
      resistant microorganism is often involved.

PMID- 14967968
TI  - [Analysis of operating costs during a year in an infectious diseases department
      (April '94-March '95)].
AB  - The Authors have analytically worked out the operating costs on the different
      pathologies for all the patients admitted at the Infectious Diseases department
      (USL Bologna City) from April 1994 to March 1995. The economic costs for one-year
      treatment of AIDS patients were very expensive for the community. In fact, for
      each patient, the average hospital admissions were 2.2 for year, and the average
      duration of hospitalization was 24 days each time. The Day Hospital had an
      important role for the majority of the patients with pathologies correlated with
      HIV infection (AIDS and ARC). The 75% of hospitalization days were spent by
      patients with HIV correlated pathologies. This group of patients caused 71% of
      diagnostic-therapeutic procedures. The number of admissions to hospital for
      patients with a pathology not correlated with HIV was lower than statistical
      expectations, probably because these patients preferred other medical services to
      avoid contacts with AIDS patients. The Authors have got the conviction that the
      existence of other kind of territorial assistance services such as House Care and
      Domiciliary Therapy Care would determine a great decrease of the operating costs.

PMID- 14967969
TI  - [Acute and chronic viral hepatitis in HIV positive patients].
AB  - In this study we evaluated the spreading of HBV, HCV, HDV and HIV among drug user
      patients. Spreading of hepatotropic viruses resulted high (HBV 84%, HCV 87%, HDV
      7%), while spreading of HIV resulted relatively low (18%). During the period
      considered we did not observe any favourable effect of hepatotropic viruses on
      the progression of HIV infection, while the chronic evolution of acute viral
      hepatitis HBV related was high (90%) in HIV+ patients. HIV infection did not
      determine different histological findings in respect to HIV- patients with
      chronic hepatitis, HBV or HCV related

PMID- 14967970
TI  - [Giardia duodenalis infections in pediatrics: our series].
AB  - 5000 pediatric patients presenting gastrointestinal disturbance (diarrhoea,
      vomiting, abdominal pain or stypsis) coming from different urban and rural area
      of Naples (Italy) were evaluated for possible intestinal Giardiasis at the
      Department of Pediatrician, University of Naples, Italy. The mean age of the
      patients was 6.4 years and range 0.5-15 years. Giardia duodenalis was searched in
      3 different specimens of stools collected every other day, by a microscopic
      examination by Stoll method. The presence of Giardia duodenalis was correlated
      with different parameters: life-style, social environment, social level, season,
      geographic area and subjective symptoms. Statistical differences in the different
      groups of patients were evaluated by the chi square test. Giardia duodenalis was
      found in 237/5000 patients (4.7%) of the patients. In nine of them the protozoa
      was associated with E. vermicularis and in 8 with T. thichiuria e the highest
      monthly prevalence was observed in November an December. The most frequent
      symptom was diarrhoea (61.1%). According to these data the Authors can conclude
      that Giardiasis is a frequent gastrointestinal infection even in children living
      in temperate areas. This infection is frequently asymptomatic, but can lead to
      malabsorption and/or to malnutrition, and can be cause of orticaria.

PMID- 14967971
TI  - [Tuberculous meningo-encephalitis in pediatrics. Considerations on 71 cases (1968
      1993)].
AB  - The tuberculous meningitis is an uncommon but severe complication of the
      tuberculosis mainly in childhood. Neurological sequelae are frequent and high
      mortality rate, till now, occurs. We reviewed the medical records of 71 cases and
      we evaluated the most frequent symptoms before the admission and signs and
      symptoms on the admission according to prognosis. An early diagnosis and specific
      anti-tuberculous treatment are essential in order to prevent permanent
      neurological sequelae and fatal outcome

PMID- 14967972
TI  - [Port malaria caused by Plasmodium falciparum a case report].
AB  - A case of unusual transmission by Plasmodium falciparum malaria is reported. The
      patient, had not been travelling outside North-West of Italy for the previous 6
      months, he was not drug abuser. He had spent the last two months prior his
      admission, partly in his home town, an urban area in the region of Piemonte, and
      partly in a resort area on the Ligurian sea. Neither place has ever been
      associated with unusual malaria transmission. The possible transmission way is
      through a live vector imported from endemic area in a port terminal near a resort
      area.

PMID- 14967973
TI  - [Health and prevention in developing countries: the original approach of the
      popular Chinese Republic in the fifties].

PMID- 14967974
TI  - [Tuberculosis and literature at the beginning of the 20th century].

PMID- 14967975
TI  - Ensuring quality preventive care: the Texas Department of Health's Put Prevention
      into Practice initiative.
AB  - In the current public health arena, assurance of quality clinical preventive
      services to all populations will be possible only if collaborations are nurtured
      between public health and the private sector health care delivery systems. This
      article explores key preventive health programs that serve as the historical
      context for the evolution of the Texas Department of Health-Put Prevention Into
      Practice (TDH-PPIP) initiative, outlines documented barriers to implementation of
      preventive services in primary care, and reviews national public health programs
      launched to reduce these barriers. Lastly, a discussion regarding the joint
      responsibilities of the public health and the private sector professionals in
      assuring quality preventive services to all populations is initiated.
      Collaborative efforts, such as the TDH-PPIP, initiative improve the availability
      and quality of clinical preventive services and, thus, result in significant
      advances in the public health goal of ensuring conditions in which people can be
      healthy.

PMID- 14967976
TI  - Utilizing "PPIP Texas style!" in a medically underserved population.
AB  - Implementation models, such as the national Put Prevention Into Practice program,
      have produced small to moderate changes in the delivery of preventive services in
      primary care. More recently, researchers concluded that guides and tools, such as
      the PPIP toolkit, are helpful, but are not sufficient to facilitate substantive
      change in clinical preventive practice. Successful implementation of clinical
      preventive services, according to the Texas Department of Health-PPIP (TDH-PPIP)
      initiative, involves creating or altering systems to produce change in service
      delivery for a specific setting. This article describes the ways in which the
      guidelines and instruments that were developed and refined through the
      collaborative efforts among public and private health systems were used to
      implement systems change and improve clinical preventive services at one
      community primary health care clinic in Texas. The process and empirical results
      of using the TDH-PPIP Implementation Model in the field are also presented, as
      well as a discussion of one-year evaluation data.

PMID- 14967977
TI  - Put Prevention into Practice implementation model: translating practice into
      theory.
AB  - Put Prevention into Practice (PPIP), a national initiative promoting evidence
      based clinical preventive services, was atheoretical in its approach to change.
      In 1994, the Texas Department of Health began demonstration projects to implement
      PPIP in grantee primary care sites across the state. They funded implementation
      and evaluation projects that resulted in eight years of experience with the
      process. Gathering both qualitative and quantitative data, the Texas Department
      of Health and the University of Texas researchers found action research essential
      to learning how to successfully support clinical sites in the implementation of
      PPIP. The researchers also found the need for on-site consultative assistance and
      a participatory problem-solving approach in order to produce desired systems
      change. A complex adaptive systems' perspective gave theoretical justification
      for action research, the composition of the PPIP Implementation Model, and the
      importance of specific adaptation by clinics. Thus, the eight-year action
      research project found that a state health department desiring to implement and
      institutionalize quality health care should focus on: (1) context-specific
      consultation, (2) recognition of complexity and system-level constructs, and (3)
      the requirement for participatory change.

PMID- 14967978
TI  - Leading by example: a local health department-community collaboration to
      incorporate physical activity into organizational practice.
AB  - A multisectoral model promoting sociocultural environmental change to increase
      physical activity levels among African Americans in Los Angeles County,
      California, was developed and implemented. This model represents a true
      collaboration between a local health department and a community lead agency.
      Community organizations serving targeted areas of the county participated in one
      or more interventions incorporating physical activity into routine organizational
      practice, which centered around modeling the behaviors promoted ("walking the
      talk"). In the current study, level of organizational support for physical
      activity integration was assessed, as reflected in the extent of organizational
      commitment associated with each intervention. Individual-level data,
      characterizing the sociodemography, health status, and health behaviors of
      organization staff, members, and clients, are presented to document the average
      risk burden in the targeted population. Nearly half of the more than 200
      participating organizations actively embraced incorporating physical activity
      into their regular work routines, with more than 25 percent committed at the
      highest level of involvement. Broad capacity and support for organizational
      integration of physical activity was demonstrated, with the observed level of
      commitment varying by organization type. Similar to the successful evolution of
      tobacco control, some of the responsibility ("cost") for physical activity
      adoption and maintenance can and should be shifted from the individual to
      organizational entities, such as workplaces.

PMID- 14967979
TI  - Unsafe neighborhoods, social group activity, and self-rated health.
AB  - The purpose of this project was to assess the importance of stressors and social
      supports in influencing self-rated health in a community sample so that public
      health programs could be designed to address the root causes of poor health. The
      municipal health department in Amarillo, Texas, contracted for a Behavioral Risk
      Factor Surveillance survey in 2002. The dependant variable for the study was self
      rated health. Results suggest that programs targeted at improving neighborhood
      safety and increasing involvement in organized social groups are needed. Public
      health agencies may need to collaborate with other governmental agencies in order
      to craft effective policies.

PMID- 14967980
TI  - Disseminating effective behavioral interventions for HIV prevention: a cost
      analysis of a risk-reduction intervention for drug users.
AB  - Economic evaluations of researched HIV-prevention interventions assist service
      providers in decision making and can help disseminate effective interventions
      into practice. The study described in this article presents a cost analysis of an
      intervention that was effective in a research setting. This article also provides
      threshold analyses that set performance standards to determine if an intervention
      is cost-effective or cost-saving. From a service provider's perspective, the cost
      for this intervention is estimated at 50306.40 US dollars for one year (for 150
      clients). The base-case, cost per client of this intervention is estimated at
      335.38 US dollars. Threshold analyses revealed that in order for Safety Point to
      be considered cost-saving, it should avert at least 0.411 HIV infections per 150
      clients.

PMID- 14967981
TI  - Aligning budget with U.S. National HIV prevention priorities.
AB  - Reducing new HIV infections in the United States requires allocating public
      resources to interventions that will have the greatest impact on reducing the
      number of new infections. We report on the organizational experience of a federal
      agency's efforts to align its HIV prevention resources to reflect the specific
      priorities of a five-year strategic plan that has as its goal a fifty percent
      reduction in the number of annual HIV infections nationwide. Structural and other
      impediments encountered during the alignment process, and the steps taken to
      minimize their impact are described, adding to the empirical data base of
      strategic planning experiences in the public sector.

PMID- 14967982
TI  - Same-day scheduling in a public health clinic: a pilot study.
AB  - Same-day scheduling, is built on the premise that today's work should be done
      today. Ensuring patients access to providers on the same day that they call their
      providers challenges a cherished assumption of medical practice management.
      Increasing dissatisfaction on the part of both patients and providers has made
      same-day scheduling increasingly popular for medical practices in both the for
      profit and not-for-profit sectors. The study described in this article reports
      the results of an experimental introduction of same-day scheduling in a public
      health clinic. Same-day scheduling resulted in shorter waiting times, lower no
      show rates (or alternatively higher show rates), more new patients, and increased
      provider productivity. The results of this pilot study were sufficient to
      convince the local health department to expand same-day scheduling to all its
      clinics and illustrate the gains that can be achieved in doing today's work
      today.

PMID- 14967983
TI  - Continuing-education needs of public health educators: their perspectives.
AB  - The objective of the study described in this article was to determine the
      perceived continuing-education needs of employed public health educators. A three
      wave mailing of a questionnaire was sent to a national sample of 500 public
      health educators who were asked to rate their preparation on 41 subcompetencies.
      Of 299 returned surveys (63%), 149 indicated that they were not currently
      practicing public health educators. Thus, analysis was based on 150 respondents.
      Six subcompetencies were perceived by 25% or more of the respondents as topics in
      which they needed more training. Health educators reported a need for continuing
      education, focused primarily on administration and evaluation of programs and
      applying appropriate research principles. Furthermore, the public health
      educators overwhelmingly preferred to attend a conference or workshop (85%) as
      their method of obtaining further continuing education. Health education programs
      and professional organizations need to take note of the identified continuing
      education needs when developing future educational programs to adequately update
      health educators.

PMID- 14967984
TI  - Organizational capacity's effects on the delivery and outcomes of health
      education programs.
AB  - Community-based public health efforts to change health behaviors and health
      outcomes generally involve the implementation of complex, multipronged programs,
      which utilize many resources, both inside and outside a single community-based
      organization or agency. It is becoming more apparent that the organizational
      capacities of these agencies influence the implementation and success of health
      promotion programs. However, research is limited on the specific organizational
      capacities (e.g., resources, training, workload, trust, communication) that
      influence program implementation and, thus, the ultimate impact of these
      programs. This article seeks to address this gap in the literature by identifying
      organizational capacity variables that may have influenced the delivery of a
      dietary change program.

PMID- 14967985
TI  - Extending the REACH of health coverage: a program for the uninsured in Anne
      Arundel County, Maryland.
AB  - The Anne Arundel County Department of Health, in Maryland, is expanding access to
      care for the uninsured through the development of the Residents Access to a
      Coalition of Health (REACH) program. The goals of REACH, developed in
      collaboration with the county medical society, are to improve the quality of
      health care, decrease unnecessary hospitalizations, and reduce usage of emergency
      room services among county residents who are ages 19 to 64. This is accomplished
      through a voluntary network of partners who have formally agreed to accept
      discounted fees for services. Over 3,200 county residents with a network of 400
      providers and three hospitals have received over 4.8 million US dollars of
      uncompensated care since the program's inception in 1999.

PMID- 14967986
TI  - Using strategy to overcome tragedy.

PMID- 14967987
TI  - Share what works: model practices in local public health agencies.

PMID- 14967988
TI  - [Promoting and supporting interdisciplinary research: the Inserm/CNRS-SHS Health
      Seminary].

PMID- 14967989
TI  - [Recovery from disability in an older population. Results of long-term follow-up
      in Upper-Normandy (France)].
AB  - BACKGROUND: The recovery of people initially disabled was addressed using the
      National Institute of Health and Medical Research Upper-Normandy survey,
      conducted on a representative sample of the older population from 1978 to 1999.
      METHODS: The survey was based on 1082 older people aged 65 and over. A follow-up
      was organized to register mortality and disability at point 3, 6, 10 and 20
      years. Among the persons initially disabled were taken into account those who
      were able to go outside their home without help during the 20-year follow-up.
      Each case of recovery was validated. RESULTS: Among the 1046 subjects for whom
      data could be analyzed, 218 presented mobility disability necessitating help to
      go outside their home. Recovery from disability was observed in 23 subjects
      (10.5%; CI: 6.5-14.5). Among the 195 subjects (89.5%) without any recovery, 107
      (49%) had died before 4 years, 44 (20%) had died between 4 and 6 years, and 44
      (20%) survived with disability more than 6 years. The rate of recovery was 18.6%
      before age 80, and 4.1% for people aged 80 and over. It was 1.3% for home
      confined or bed- or chair-confined people and 15.4% for the others. Before age 80
      the recovery rate was significantly higher in women. No recovery was observed for
      people with mental deterioration. Cerebrovascular diseases were significantly
      associated with a low rate of recovery (5%). CONCLUSIONS: Recovery from
      disability should be taken into account for the health prospects of the elderly
      population. It concerns about one person out of five before the age of 80.
      Increased rate of recovery after the age of 80 should be one of the objectives
      for the health system in the future.

PMID- 14967990
TI  - [Recovery from disability in an older population. Long-term follow-up of disabled
      elderly persons].

PMID- 14967991
TI  - [The access to care of underserved populations: a research among free clinics
      patients in the Paris area].
AB  - BACKGROUND: Over the last decade, the increasing number of people experiencing
      difficult social conditions--especially in urban areas--has led to the
      implementation of free (health and social care) clinics for uninsured and/or poor
      people. METHODS: In this paper, we give some results of multidisciplinary
      (sociological and epidemiological) research conducted among patients attending
      five of these free clinics in the Paris area. RESULTS: The statistical and
      qualitative analyses revealed the diversity of the studied population, as well as
      the conditions in which these consultants attended such clinics, what kind of
      services and help they used and, furthermore, what kind of social ties were
      strengthened. CONCLUSION: These results lead us to discuss our present knowledge
      of the determinants of the utilization of the healthcare system, not only among
      vulnerable people, but perhaps also amongst the general population.

PMID- 14967992
TI  - [Questioning employees on their professional past: the meaning of
      inconsistencies].
AB  - BACKGROUND: Reflecting on professional careers is essential to understand aging
      at work. In most cases, the only way to gain knowledge on the occupational
      history of workers is to question them directly. The purpose of this study is to
      reflect on the quality and meaning of the answers employees give when asked about
      the "course" of their work. METHOD: The present analysis pertains to the ESTEV
      survey on health, work and aging. For occupational health purposes 21,400
      employees of both sexes, representing four different age years were asked to
      respond to a questionnaire in 1990; five years later, more than 87% of them were
      seen again. The longitudinal analysis shows that an individual's responses on
      past and present working conditions may be inconsistent. The methodology applied
      aims to "find a meaning" for such inconsistencies, both by confronting them with
      other data from the ESTEV survey and by clarifying the process leading to the
      construction of such inconsistencies through further inquiries among the
      respondents concerned. RESULTS: By not considering these inconsistent responses
      to be "errors" one gathers a clearer understanding of how the perception
      employees have of their own working conditions may change over time. CONCLUSION:
      The present study stresses the importance of confronting qualitative and
      quantitative approaches to gain useful knowledge on the phenomena at hand.

PMID- 14967993
TI  - Job stress and occupational status in a French cohort.
AB  - BACKGROUND: The goal of this study was to examine a large, varied occupational
      French cohort for possible relationships between various dimensions of
      occupational stress, on the one hand, and the occupational status and socio
      demographic characteristics of workers on the other. METHODS: Data was taken from
      the first, cross-sectional phase of the VISAT study (aging, health, and work),
      which took place in 1996. Participants were randomly drawn from the patient lists
      of about one hundred occupational physicians in three regions of southern France.
      The current study concerned 2,768 wage earners born in 1944, 1954, or 1964. The
      material consisted of 59 questions aimed at assessing a broad set of working
      conditions, some of which were proxy measures of the dimensions described in the
      Karasek and Siegrist models. RESULTS: From a principal component analysis, three
      main factors were extracted that accounted for 40% of the total variance. The
      first factor (a=0.79) included items that referred to the decision latitude in
      the Karasek model and items that referred to the reward dimension in the Siegrist
      model. The second factor (a=0.77) was made up of items tapping physical
      stressors, while the third factor (a=0.71) pooled items that corresponded fairly
      well to psychological demands in the Karasek model. Highly significant
      relationships (p<10(-4)) were found between the mean factor scores and both
      occupational status and educational level, with a lower occupational status and
      educational level being associated with greater lack of job control and rewards,
      higher physical stress, but lower psychological demands. Less job control and
      fewer rewards were also found to be greater in older workers (p<10(-3)) and
      females (p<10(-4)). CONCLUSION: Our results thus confirm the existence of a
      strong association, in a French cohort, between occupational status and
      dimensions of job stress known to be associated with adverse health outcomes.

PMID- 14967995
TI  - [The use of prenatal diagnosis testing: what can be learnt from economic analysis
      of individual decision-making?].

PMID- 14967994
TI  - Socioeconomic and state-level differences in prenatal diagnosis and live birth
      prevalence of Down's syndrome in the United States.
AB  - BACKGROUND: Previous studies have shown socioeconomic disparities in the use of
      prenatal diagnosis in several countries, including France and the United States.
      Few studies however, have examined the impact of socioeconomic differences in
      prenatal testing on disparities in the live birth prevalence of congenital
      anomalies. In this article, we first review and further discuss some of the
      results of our previously published work that assesses: i) socioeconomic
      differences in the use of amniocentesis in the United States using data from
      national birth cohorts; and ii) impact of socioeconomic differences in prenatal
      diagnosis on the live birth prevalence of Down's syndrome (trisomy 21). We then
      present the results of a study that explores the potential effects of public
      policies regarding abortion on state-level differences in the live birth
      prevalence of Down's syndrome. MATERIALS AND METHODS: We used birth data from the
      National Center for Health Statistics for the years 1989 to 1991 as well as data
      from the National Abortion and Reproductive Rights Action League (NARAL) state-by
      state review of abortion rights. The main individual-level socioeconomic
      variables in the analyses were maternal ethnicity and education; the analyses of
      the interaction effects between maternal age and ethnicity are presented here.
      Interaction effects were assessed using logistic regression models with
      likelihood ratio tests. We used hierarchical logistic regression models for
      analyses of state-level effects while controlling for individual-level
      socioeconomic factors. RESULTS: We found substantial age-specific socioeconomic
      differences in the use of amniocentesis and in the rates of age-related increase
      in the live birth prevalence of Down's syndrome. In particular, African Americans
      and Mexican Americans were found to have lower odds of amniocentesis use and
      higher odds of Down's syndrome at birth. In addition, after controlling for
      maternal age, socioeconomic factors and prenatal care, we found that states which
      allowed public financing of abortion services for all or most circumstances had
      lower odds of Down's syndrome at birth. CONCLUSION: Unless socioeconomic
      differences in prenatal testing are addressed, the increasing use of prenatal
      testing might result in widening socioeconomic disparities in the live birth
      prevalence of Down's syndrome and other major congenital anomalies in future
      years.

PMID- 14967996
TI  - [Access to health care for an induced abortion: qualitative and quantitative
      approaches].
AB  - BACKGROUND: Despite recent studies showing evidence that the organisation of the
      French health care system raises some problems concerning access to abortion, far
      little is known on the reality of access conditions and the views of women on the
      difficulties they experience when they attend an abortion clinic. In this
      article, we discuss the complementarity of materials from two surveys one
      qualitative, the other quantitative in the study of patterns of care for an
      abortion. METHODS: The qualitative survey included 51 women who reported a
      history of induced abortion, selected from a qualitative study on unintended
      pregnancy in France. The quantitative survey included 480 women, who had an
      abortion in the past 10 years. These women were selected from a representative
      sample of 2863 women aged 18 to 44, who participated in a study on contraception
      and abortion. RESULTS: The variety of patterns of care for an abortion, the
      rareness of dysfunctions in the health care system and the importance of the
      first professional women contacted, demonstrated in the qualitative survey, were
      confirmed in the quantitative survey. The quantitative survey enabled quantifying
      the distribution of the different patterns of care. It also permitted to identify
      factors associated with the choice of first professional contacted and with the
      type of subsequent patterns of care. The qualitative survey permitted to explore
      these patterns of care and to highlight the interaction between the women's
      request and the representation of the legitimacy of their request. Difficulties
      of access seemed to be linked to the lack of support women experienced in the
      process of finding an abortion clinic. Results suggest that general practitioners
      are less well informed of the procedures required for an abortion than other
      professionals. However, the qualitative survey also shows that problems of access
      cannot be reduced to the lack of information of professionals, as their practice
      was also linked to their own representation of abortion, and their perception of
      the legitimacy of the women's request. CONCLUSION: Our results underline the need
      for the definition of a clear health policy that should include two priorities:
      the improvement of the visibility of health care supply for an abortion and the
      promotion of information delivered to health care professionals.

PMID- 14967997
TI  - [Developing home-care hospitalization: cost evaluation and assessment criteria.
      The case of anticancer chemotherapy].

PMID- 14967998
TI  - [Intraoperative and early postoperative complications of lumbar and lumbosacral
      fusion: prospective analysis of 872 patients].
AB  - PURPOSE OF THE STUDY: Incidence of complications following lumbar or lumbosacral
      fusion is still an imprecise notion. The aim of this prospective observational
      study was to determine the frequency of intraoperative and early postoperative
      complications after this procedure and to analyze favoring factors. MATERIAL AND
      METHODS: Twenty-one orthopedic units participated in this study which included
      872 patients who underwent lumbar or lumbosacral fusion procedures involving the
      sector limited by L1 and S1. A minimum of 6 months follow-up was required for
      inclusion. Four types of complications were studied: general complications,
      infection, neurological and meningeal complications, mechanical problems. The
      following preoperative and intraoperative parameters were recorded:
      epidemiological and morphological data, history of lumbar spine surgery, comorbid
      conditions, indication for surgery, and technical aspects of the fusion. Two
      types of analysis were performed. The first was a descriptive analysis designed
      to determined the overall incidence of complications and the incidence of each
      type of complication. A multivariate analysis was then performed in order to
      determine factors influencing occurrence of complications. RESULTS: Mean follow
      up was 13 months, mean age of the cohort was 51 +/- 15.5 years. Prior lumbar
      surgery was noted in 12% of the patients. A decompression procedure was
      associated in 40% of the patients due to lumbar stenosis. Posterolateral
      arthrodesis was used in 71% of the patients and 91% were instrumented. Most of
      the fusions were short, involving one or two levels. One or more intraoperative
      or early postoperative complications were observed in 200 patients (23%). The
      incidences of the four types of complications expressed in percent of the total
      cohort were 9.7%, 5.6%, 8.6%, and 3.6% for general, infectious, neurological and
      meningeal, and mechanical complications respectively. Three factors exhibited a
      significant correlation with occurrence of complications, irrespective of the
      type: excess weight, presence of several comorbid conditions, and extent of the
      zone of fusion. CONCLUSION: This study enabled a precise assessment of the
      incidence of complications subsequent to lumbar or lumbosacral fusion: 23%. The
      incidence of serious complications requiring a reoperation was 14.7%. This
      finding, together with the factors found to influence occurrence of these
      complications should be kept in mind when determining indications for lumbar or
      lumbosacral fusion.

PMID- 14967999
TI  - [A new implant for proximal humeral fracture: experimental study of the basket
      plate].
AB  - PURPOSE OF THE STUDY: We conducted a comparative study of three ostheosynthesis
      systems for proximal humeral fractures. The conclusions led to the elaboration of
      a rigid extramedullary osteosynthesis implant. This novel implant allows specific
      fixation of the tuberosities via six adjustable and removable hooks organized
      like a basket. There are two versions, with and without a central cephalic
      locking screw. We report two static biomechanical studies conducted to analyze
      this material. MATERIAL AND METHODS: The two studies were performed on fresh
      frozen cadaver specimens with known bone density and with an experimental model
      of a four-fragment fracture of the proximal humerus. The first tests were
      designed to measure axial pressure reproducing the physiological movement
      applying the most stress on the head of the humerus. This allowed a global
      analysis of the mechanical behavior of the implant and an assessment of the
      contribution of the central cephalic locking screw. The second series of tests
      were traction tests used to analyze the behavior of the tuberosities fixed with
      the hooks. We assess the assemblies by measuring the mechanical resistance:
      rigidity of the fixation was recorded in mm/100N. Pre- and post-procedure x-rays
      and photographs were obtained to allow a subjective assessment of fragment
      displacement. RESULTS: The first series of tests demonstrated that the implant,
      with the central cephalic locking screw, presented good overall mechanical
      properties. The notion of better stability of the tuberosities obtained with the
      hooks, as seen during the first tests, was reinforced by the data from the second
      tests, although no statistically significant difference was demonstrated. We also
      noted that there was no statistically significant correlation between bone
      density and the slopes of the force-resistance curves. DISCUSSION: This prototype
      implant has an overall mechanical resistance equivalent to the reference implant,
      with at least equivalent performance. Proof of the usefulness of the central
      locking screw was not established, even though improved tolerance to loading by
      better force distribution seemed apparent. The contribution of the hook basket
      was not demonstrated. Data from the observations do however suggest the
      expectations of the implant will be fulfilled. Tests conducted on a larger scale
      would probably demonstrate a difference. It is clear that the small number of
      implants used here limited the study. Comparison with data in the literature show
      that this new prototype is adapted to the mechanics of the proximal humerus.
      Resistant to physiological stress, the implant allows pendular movement and
      passive physical therapy during the early post-operative period.

PMID- 14968000
TI  - [High incidence of total hip arthroplasty aseptic loosening with ion-coated
      titanium femoral heads].
AB  - PURPOSE OF THE STUDY: The purpose of this study was to determine the frequency of
      aseptic loosening among a series of total hip arthroplasties evaluated at 84
      months and to search for the cause. Two types of acetabular cups had been
      implanted. It was hypothesized that the ion coating of the titanium head could be
      involved in the deterioration of titanium/polyethylene implants. MATERIAL AND
      METHODS: Two non-cemented acetabular cups differing only by the presence or not
      of a hypoxyapatite coating were studied. Different types of femoral heads
      (stainless steal, chromium-cobalt, alumina, zincrona, nitrurated titanium, ion
      coated titanium) and femoral stems (with or without cement) were implanted. Sixty
      two ion-coated titanium heads were implanted and 47 patients with 52 heads were
      reviewed. Clinical outcome was assessed with the Postel-Merle-d'Aubigne score and
      the Livermoore method was used for radiological assessment of the bone-implant
      interface and polyethylene wear. The physico-chemical properties of one titanium
      head explanted after aseptic loosening were also studied. RESULTS: At 84 months
      follow-up, the mean clinical score was 15.8/18 points. Mean polyethylene wear was
      0.18 mm/year. There were 13 revisions for aseptic loosening: two bipolar, nine
      acetabular and two femoral. Mean wear for the explanted implants was 0.34
      mm/year. Metallosis was observed in eight cases. Arthroplasties with the same
      types of femoral stem and acetabular implants but with other types of heads
      (stainless steal, chromium-cobalt, alumina, zincrona, nitrurated titanium) led to
      only one case of aseptic loosening among 118 implantations. Electron microscopy
      demonstrated the presence of scratch lines, disappearance of the nitrogen ion
      layer, decreased hardness, and increased roughness of the titanium head.
      DISCUSSION: The poor friction properties of titanium are well known. To improve
      performance, ion coating has been proposed. This technique consists in projecting
      nitrogen ions onto the surface of the head to form a surface coating measuring
      about one micron. The high incidence of aseptic loosening, polyethylene wear,
      metallosis, and modifications of the head surface (disappearance of the nitrogen
      ion layer, scratch marks, etc.) suggest ion-coated titanium heads could be the
      cause of these aseptic loosenings. CONCLUSION: Ion-coating has not provided good
      protection of the titanium head. Patients with this type of head should be
      followed carefully in order to detect aseptic loosening or metallosis early.

PMID- 14968001
TI  - [Isokinetic evaluation of the knee flexor muscles after anterior cruciate
      ligament reconstruction using gracilis and semitendinous tendon grafts].
AB  - PURPOSE OF THE STUDY: The purpose of this study was to evaluate recovery of
      hamstring force after anterior cruciate ligament reconstruction using gracilis
      and semitendinous tendon grafts. MATERIAL AND METHODS: Isokinetic evaluation of
      the knee flexor muscles was performed with the system 3 Biodex isokinetic
      dynameter in twelve patients (mean age 26 years) 12 to 24 months after
      ligamentoplasty. Concentric (60 degrees /s, 180 degrees /s, 300 degrees /s) and
      excentric forces were measured. We retained for analysis: 1) moment of maximal
      force, 2) moment of force at 75 degrees knee flexion, and 3) work. RESULTS: The
      knee flexor muscles of the operated limb exhibited greater deficit when
      considering force at 75 degrees knee flexion (24%, 15%, and 18% concentric
      deficit at 60 degrees /s, 180 degrees /s, and 300 degrees /s respectively, and
      20% excentric deficit) than when considering maximal force (14%, 7%, 5%
      concentric deficit at 60 degrees /s, 180 degrees /s, and 300 degrees /s
      respectively and 9% excentric deficit). DISCUSSION: This study demonstrates
      persistent deficit of knee flexor muscle force 12 to 24 months after anterior
      cruciate ligament repair with hamstring muscle tendons. The deficit reaches 15%
      to 24% at 75 degrees of knee flexion. The protective role of the hamstring
      muscles for the cruciate graft submitted to important stress may be compromised
      by the lack of recovery of knee flexor force more than one year after
      ligamentoplasty.

PMID- 14968002
TI  - [Trauma-induced tears of the quadriceps tendon: 47 cases].
AB  - PURPOSE OF THE STUDY: A torn quadriceps tendon is an exceptional finding
      generally observed after high-energy knee trauma in patients over 40 who present
      a sprain-like syndrome or after low-energy trauma in elderly subjects who
      experience knee instability. We reviewed a series of 47 cases of traumatic
      quadriceps tendon tears treated between 1976 and 1996 in order to evaluate
      outcome after surgical repair. MATERIAL AND METHODS: Clinical diagnosis was the
      rule. Forty-two patients, mean age 55 years (range 17-92) were treated for tears
      of one or both quadriceps tendons subsequent to low-energy trauma (40 tears) or
      high-energy trauma in younger subjects. The diagnosis was established early in
      all cases except eight (diagnosis at three weeks to one year). Surgical repair
      was performed in all cases except one. After surgery, the knee was either
      immobilized with a plaster cast or held in a removable splint to allow early
      mobilization. RESULTS: Average time to recovery compatible with daily life or
      occupational activities was four months. Recovery was not complete at this time.
      Long-term follow-up revealed that complete recovery with very good or good
      subjective results was achieved in 90% of the cases. Complete joint motion and
      normal quadriceps force was achieved in 80% of the cases. Patients who started
      rehabilitation exercises early generally achieved less satisfactory results
      although no significant correlation was identified with objective clinical
      variables. DISCUSSION: Quadriceps tendon tear is a clinical diagnosis which does
      not require complementary exploration for confirmation. Plain x-rays may be
      useful to identify associated bony lesions and specific signs of tendon tears.
      Early surgical repair followed by complete immobilization appears to be
      preferable for functional recovery allowing better recovery of muscle force
      without compromising flexion.

PMID- 14968003
TI  - [Revision total knee arthroplasty after unicompartmental femorotibial prosthesis:
      54 cases].
AB  - PURPOSE OF THE STUDY: We analyzed technical difficulties encountered when
      performing revision total knee arthroplasty in patients with unicompartmental
      femorotibial prostheses. MATERIAL AND METHODS: This multicentric retrospective
      study included 54 revisions of unicompartmental femorotibial prosthesis with
      implantation of a total knee prosthesis. The series included 45 medial and nine
      lateral compartment prostheses. A gliding total knee prosthesis was implanted in
      53 cases (98%) (39 standard, 14 revision). Mean time to failure of the
      unicompartmental prosthesis was four years. IKS scores were established at
      review. The radiological work-up included AP and lateral views in single leg
      stance and goniometry for 22 medial compartment revisions. Twenty-seven patients
      were seen for physical examination and x-rays and eight were lost to follow-up;
      data were recorded from medical files for 19 patients. RESULTS: The revision
      procedure was considered easy in 82% of the cases. Mean follow-up after revision
      was four years (range 2 - 12 years). Subjective outcome was very satisfactory for
      56% of the patients, satisfactory for 36% and unsatisfactory for 8%. The mean
      function score was 62 points, the mean knee score 85 points, and the mean flexion
      was 113 degrees. No laxity was found for 90% of the knees. The femorotibial angle
      was 180 +/- 2 degrees in 46% of the patients. The mechanical femoral angle was 90
      degrees in 54% of the patients with 2-4 degrees varus in 42%. The mechanical
      tibial angle was 90 degrees in 46% of the patients with 2-8 degrees valgus in
      37%. Complications included pulmonary embolism (n=2), mobilization under general
      anesthesia (n=3), arthrolysis (n=1), lateral vertical patellectomy (n=1), and
      secondary infection (n=1). There were five failures requiring changing the total
      knee prosthesis. DISCUSSION: Loss of bone stock raises specific problems during
      revision of unicompartmental knee prostheses. Loss of tibial bone is more
      frequent but it is more difficult to correct for loss of femoral bone. A gliding
      knee prosthesis is generally preferred for first intention revision. We recommend
      a long stem when the bone defect is important or involves loss of cortical bone.
      We have had good mid-term results with revision total knee prostheses after
      unicompartmental prostheses. Longer follow-up is needed. Poor results were
      obtained when revision was performed for persistent pain without a clearly
      defined cause. The presence or not of significant bone loss did not appear to
      affect outcome. The observation of medial laxity in case of failed lateral
      unicompartmental prostheses suggests a more constrained total knee prosthesis
      might be indicated. Compared with earlier series, our results with total knee
      prostheses after unicompartmental prostheses appear to be better than after
      tibial valgus osteotomy and also better than after total knee arthroplasty.
      Conversely, they would be less satisfactory than for primary total knee
      arthroplasty. The surgical procedure for revision total knee arthroplasty after
      unicompartmental prosthesis requires precision and skill but is not technically
      difficult.

PMID- 14968004
TI  - [Knee arthrodesis using a customized intramedullary nail: 14 cases].
AB  - We report our experience with knee arthrodesis using a customized intramedullary
      nail implanted in 14 patients. Indications for knee arthrodesis were: recurrent
      prosthesis infection (n=11), post-traumatic septic arthritis (n=1), aseptic
      loosening of a hinge prosthesis (n=1), and nonunion (n=1). A two-stage procedure
      was used for the 12 patients with infected joints. Mean follow-up was 19 months.
      Weight bearing began during the first week after arthrodesis in 13 patients.
      First intention bone healing was achieved in 13 patients. Mean time to healing
      was three months. All patients rapidly recovered full independence. Complications
      were: one misinsertion of the tibial stem, one nonunion which fused after
      repeated grafting, and two recurrent infections (controlled chronic fistulae)
      which required skin flaps for cover. We have found that this customized nail is a
      useful method for achieving bone fusion in patients with difficult indications
      for arthrodesis, particularly recurrent prosthesis infection.

PMID- 14968005
TI  - [Arthroscopic knee arthrodesis: 4 cases].
AB  - PURPOSE OF THE STUDY: Arthroscopic arthrodesis of the knee joint is an
      alternative to classical surgery, which retains a few exceptional indications. We
      report the first four cases of our experience, describing the technical
      modalities and indications. MATERIAL AND METHODS: The four patients had undergone
      multiple operations for severe trauma. All four had persistent severe pain with a
      very limited walking distance. Before the procedure, the IKS score ranged from 11
      to 44 and the mean function score was 20 to 45 points. Arthroscopic arthrodesis
      was proposed after several consultations and took into account the young age of
      the patient and a positive brace test. The successive arthroscopic times were:
      exploration and adherence release, complete extramural meniscectomy, joint
      surface avivement. Traction was not necessary. Careful avivement spared the
      anatomic curvatures of the condyles and slightly scraped out the plateaus.
      Finally, the arthrodesis was fixed in correct position under fluoroscopy using a
      single tube external fixator. The fixation was maintained until fusion
      (satisfactory x-ray and no pain). RESULTS: A drain was inserted only for the
      first patient. There were no cutaneous complications. Patients were discharged
      after 3 days on the average with immediate simulated weight bearing using two
      crutches. The external fixator was dynamized at two months (mean) and removed at
      five months. The functional gain was considerable in four patients, assessed at
      two years, with a mean IKS score of 75 and a mean function score of 80. The four
      patients walked without crutches and without pain. Single leg stance was stable.
      Final leg shortening was 1 to 2 cm. CONCLUSION: The arthroscopic approach
      provides several benefits: uneventful postoperative period, little bleeding, no
      cutaneous complications, shorter hospital stay. The time to fusion appears to be
      shorter than with classical techniques, but cannot be demonstrated clearly
      because of the diversity of the series reported in the literature. Arthroscopic
      arthrodesis does not require any special instruments, but does require surgical
      skill and a lengthy procedure. When arthrodesis is required the arthroscopic
      procedure is indicated for minimally deformed knees without major loss of bone
      stock.

PMID- 14968006
TI  - [Para-articular osteochondroma: a case report].
AB  - Para-articular osteochondroma, a benign osteoarticular tumor which develops near
      joints, is, unlike classical osteochondroma, extremely rare. We present the case
      of a 59-year-old woman who developed a calcified mass in the infrapatellar
      region. The differential diagnosis between chondrosarcoma, synovial
      chondromatosis, and para-aticular osteochondroma was only possible after
      resection and pathology examination of the surgical specimen.

PMID- 14968007
TI  - [Muscular tuberculosis: an unusual focus of Koch bacillus].
AB  - We report an exceptional case of tuberculosis in an 8-year-old girl. The focus of
      infection was situated in the anterior muscle compartment of the left thigh.
      Diagnosis was established on the basis of histological findings. A 12-month
      antituberculosis regimen was given. Outcome was good with no general or
      functional sequelae. Based on this case and data reported in the literature, we
      discuss the routes of dissemination of the Koch bacillus explaining this unusual
      sporadic localization.

PMID- 14968008
TI  - [Progressive intra-acetabular dislocation of bipolar hip prostheses: four cases].
AB  - Certain complications, such as acetabular erosion or cup dissociation, are
      specific to bipolar prostheses. Progressive intra-acetabular dislocation has not
      been reported to date. We report 4 cases. Four elderly women developed
      progressive intra-acetabular dislocation after implantation of a bipolar
      prosthesis for femoral neck fractures. The metal-backed cup verticalized
      progressively and the ball gradually dislocated into the acetabulum, eroding it.
      Revision was undertaken with a hemispheric bone ingrowth cup and partial
      grafting. Follow-up was then uneventful. This phenomenon is different from the
      acute intra-acetabular dislocation that may occur after rupture of the anti
      dissociation mechanism (polyethylene ring) incorporated in the design of new
      implant models, or after dissociation between the ball and the cup during closed
      reduction of a dislocation, the cup catching on the acetabular rim. It is not due
      to a variation in the neck-head angles (we observed varus, valgus, and neutral
      angles) nor to a problem between the modular head and the neck (at the morse cone
      taper). For us, the cause of this progressive intra-acetabular dislocation is
      poor cup design associated with a weak retention system. If the centers of the
      inner and outer spheres are superimposed, the cup has a natural tendency to drop
      into varus because of its weight. This becomes even worse if the center of the
      outer sphere is medial to the ball center. The cup should be designed so that the
      center of the outer sphere (bipolar cup) lies lateral to the center of the inner
      sphere (ball) creating a valgus torque for the cup. Designing a bipolar cup is
      not as a simple matter as it may seem. We emphasize the importance of the
      position of the rotation centers.

PMID- 14968009
TI  - [Severe angular deformity of the humerus: unilateral external fixation for
      correction and bone lengthening].
AB  - We report the case of a 10-year-old child who presented a severely deformed upper
      limb due to post-traumatic partial proximal epiphysiodesis of the humerus. The
      goal of treatment was to correct the severe angular deformity, prevent
      recurrence, and lengthen the humerus 6 cm. We used the De Bastiani callotasis
      method with osteotomy of the humeral shaft and unilateral external fixation
      (Orthofix LRS). The bony deformations were corrected progressively. Angular
      correction induced a geometric lengthening sufficient to match the length of the
      healthy limb. Lengthening index was 22.7 days/cm. The functional and esthetic
      results were remarkable. Complementary epiphysiodesis of the proximal physis
      successfully prevented recurrent deformation.

PMID- 14968010
TI  - [Proximal 4-part humerus fractures treated by antegrade nailing with self
      stabilizing screws: 31 cases].

PMID- 14968011
TI  - [Transcultural approach in perinatality].
AB  - Over the last years, our approach to the perinatal period has become more complex
      with the integration of new tools designed for better comprehension and cultural
      awareness. In this area of medical practice, perhaps more than in others, the
      complementary contribution of different approaches, ways of thinking, and
      practical interventions is essential. Pregnancy, delivery, early mother-infant
      interactions, and construction of the parent-child relationship involve not only
      profoundly intimate, intrapsychic and intersubjective events but also medical,
      social, and cultural events which all become a part of the process of
      transmitting life in an open group. The junction between somatic, intrapsychic,
      intersubjective and cultural elements was analyzed in the everyday clinical
      setting of a multicultural suburban area near Paris. The therapeutic impact of
      this perspective was noted. Two therapeutic processes specific to the perinatal
      period were studied: the need to assist vulnerable migrant mothers in
      reconstructing their defense systems (possible because of the psychic
      transparency and the primary maternal priority of this special period of life)
      and direct work with the baby. Working directly with the baby and not only the
      mother creates an open triad around the baby. This baby/mother/therapist group
      relationship develops progressively and is initially perceived as a virtual group
      before developing into a more concrete transferential relationship based on
      familial and social resources. The perinatal clinic is by definition a very
      pluridisciplinary and very context-related unit.

PMID- 14968012
TI  - [Sickle cell disease in the neonatal period].
AB  - The prognosis of pregnancy in women with major sickle cell syndromes has improved
      greatly in recent years. Correction of maternal anemia with programmed
      transfusion has been a major advance. Rates of preterm birth and intra-uterine
      growth retardation nevertheless remain high in this population. A newborn
      affected with sickle cell disease does not develop complications of the disease,
      because the predominant fetal hemoglobin cannot co-polymerize with sickle
      hemoglobin. The rate of complications increases as the infant's hemoglobin
      synthesis switches from fetal to sickle hemoglobin. Neonatal screening of sickle
      cell disease patients enables early implementation of a comprehensive prevention
      program (daily antibiotic prophylaxy, immunization, parental education.). A
      neonatal screening program, targeted with regard to the parents' ethnic
      background, has been implemented throughout metropolitan France since 1999. In
      2002, this program enabled early diagnosis of sickle cell disease in 313
      newborns.

PMID- 14968013
TI  - [Cancer and pregnancy: obstetrical aspects].
AB  - The diagnosis of cancer in a pregnant woman raises serious problems for the
      obstetrician and the oncologist. Many diagnostic and therapeutic procedures
      cannot be implemented during gestation due to the risk of fetal complications. At
      the same time postponing radiotherapy or chemotherapy until after delivery would
      expose the patient to excessive risk. Optimal management practices remain to be
      fully described and few randomized studies have addressed the problem. There is
      the additional question of how best to preserve fertility.

PMID- 14968014
TI  - [Cancer and pregnancy: the medical oncologist's point of view].
AB  - Having to start chemotherapy during pregnancy remains a rare event. The decision
      to proceed with this treatment depends on the drugs used, the time of exposure
      for the fetus and the gestational age at the time of exposure. The mutagenic
      potential of the chosen drug has to be known. The risk for the child can then be
      established without compromising the mother's chances of survival or well-being.
      This type of situation generally arises in women with breast cancer, leukemia or
      lymphoma. The first trimester of pregnancy, which corresponds to organogenesis is
      the most critical period for the fetus. The greatest risk of malformation occurs
      with anti-metabolite drugs. Chemotherapy can also expose the child to direct in
      utero toxicity. Myelosuppression is the most common toxic effect, sometimes
      giving rise to infections and/or fetal hemorrhage. The long-term risks of cancer
      on the mother's subsequent fertility or the child's intellectual development are
      not well-known. Such factors must be examined in prospective studies and
      registered in a specific database.

PMID- 14968015
TI  - [Cancer and pregnancy: risks of exposure to cancer chemotherapy during
      pregnancy].
AB  - Animal studies reveal that almost all antineoplastic agents are teratogenic. But
      extrapolation to human beings is not simple because of species differences. Few
      human data are available, most are sporadic case reports. Other toxic effects for
      the fetus and neonate (intrauterine exposure during second and third trimester)
      must be taken in consideration when prescribing chemotherapy for pregnant women.
      Adverse effects observed in adult and children are helpful if data during fetal
      life are lacking. Long-term studies are needed to evaluate the transplacental
      effects of chemotherapy during pregnancy; these studies should assess the child's
      mental and physical development, infertility and the occurrence of second
      malignancies.

PMID- 14968016
TI  - [The use of supplements in pregnancy].
AB  - It is common practice to prescribe supplementation for pregnant women, but is it
      useful? We detail here the main deficiencies and their risks. We conclude that
      low-dose iron and folic acid, vitamin D and iodine supplementation is indicated
      for women living in France. Other systematic supplementations are not necessary
      outside pathological situations.

PMID- 14968017
TI  - [Mode of delivery and term breech presentation in the PREMODA cohort].
AB  - OBJECTIVES: The purpose of this work was to report labor and birth management
      practices for term breech presentation in France and Belgium in 2001-2002 and to
      describe indications for cesarean sections (before labor, emergency situations)
      in breech presentations. MATERIAL AND METHODS: The PREMODA cohort is a survey
      population which included 19408 deliveries, 8108 of which were term breech
      presentations. RESULTS: Infants were delivered by cesarean section before labor
      (59.1%), emergency cesarean section during labor (18.4%) or vaginally (22.5%).
      The decision for cesarean section before labor was empirical (breech
      presentation) in 44.3% of the cases. Half of the cesarean sections performed
      during labor (n=704, 49.3%) were planned C-sections. Overall, 67.8% of the breech
      presentations were delivered during planned cesarean sections (before or during
      labor). When vaginal delivery was attempted, the rate of vaginal birth was 70%.
      CONCLUSION: These early results reveal a high rate of cesarean section as well as
      differences in inter-regional practices. Considering all cesarean sections
      performed before labor, the most frequent indication was an empirical decision
      because of the breech presentation. An increased rate of planned cesarean section
      does not reduce the rate of vaginal delivery when attempted.

PMID- 14968018
TI  - [The therapeutic role of tocolysis].
AB  - In twin pregnancies, the use of beta-adrenergics is associated with a
      significantly higher incidence of cardiovascular complications, and calcium
      channel blockers as well as oxytocin antagonists currently appear as first line
      agents. After extreme preterm delivery of the first twin and in selected
      patients, the birth of second twin may be delayed with a mean gain of 10-50 days.
      In cases of symptomatic placenta previa with mild-to-moderate bleeding, tocolytic
      agents may be associated with a prolongation of pregnancy and increased birth
      weight without significant impact on frequency or severity of bleeding. Calcium
      channel blockers are the drugs of choice in the event of diabetes. Indomethacin
      is a potent tocolytic, in particular in patients with polyhydramnios. However, it
      may cause oligohydramnios, premature closure of the ductus arteriosus and
      intrauterine fetal death when high doses are administered for a duration
      exceeding 48 to 72 hours, particularly beyond 32 weeks' gestation. The neonatal
      complications of indomethacin occur frequently. Tocolysis appears to reduce the
      failure rate of external cephalic version at term.

PMID- 14968019
TI  - [One more step in network development: a community-based perinatal program].
AB  - In France, a wide range of healthcare workers provide care for pregnant women and
      their infants including general practitioners and specialists working in a
      private or public setting and midwives (again in a private or public hospital
      practice). The respective competencies of each category of healthcare workers is
      not currently evaluated and their individual actions are rarely coordinated. This
      raises the question of equal opportunity for future mothers. In light of this
      situation, we developed an innovating concept aimed at improving pregnancy follow
      up in a coordinated effort implicating all the different categories of healthcare
      workers involved in perinatal care: the pregnancy follow-up perinatal community.

PMID- 14968020
TI  - [Follow-up network for newborns with a handicap risk: experience of the Pays-de
      la-Loire network].
AB  - Newborns are given attentive perinatal care but the organization of further
      follow-up can be haphazard. The main consequences are the difficulties parents
      have in finding appropriate medical assistance for caring for high-risk infants
      and the absence of appropriate surveillance or efficient care. An inpatient
      outpatient healthcare network enables early care of these infants and can reduce
      the consequences of neurosensorial sequelae. The overall impact of the regional
      perinatal care can also be evaluated. Such a network has been implemented in the
      Pays de Loire region in France since early 2003. In six months, among 1000
      initially included infants, 500 were followed by pediatricians working in an
      outpatient (40%) or inpatient (60%) setting. This organization enables correction
      of over-centralization of neonatal care and the absence of coordination for
      follow up.

PMID- 14968021
TI  - [First trimester Down syndrome screening program using nuchal translucency and
      maternal serum markers: the Echo PAPP-A.78 study].
AB  - Successive development of different methods to screen down syndrome (DS) have had
      unexpected effects, leading to an inflation in the number of karyotypes ordered
      and the number of induced abortions. In our district (Yvelines, France), DS
      screening leads to perform 16% karyotypes rate. Rapid progress in biology and
      ultrasonography has enabled us to correct this overprescription by conducting an
      early screening program using a combination of ultrasound graphic and new
      biochemical markers (Pregnancy-associated plasma protein A and the free fraction
      of ss-hCG) which allow an overall evaluation of risk. This method has high
      sensitivity (85%) and leads to a false positive rate karyotypes in about 5% of
      pregnancies. The purpose of the study conducted between January 1, 2001 and
      December 31, 2002 in the Yvelines was to confirm the validity of this method and
      determine its reproducibility in routine practice. Five partners contributed to
      the study: the Regional delegation for clinical research of the Paris-public
      assistance hospitals (AP-HP), the district health insurance fund (CPAM 78), the
      Yvelines maternity network which includes all ten maternity wards in the
      district, and the Echo 78 association which includes all ultrasoundgraphists
      working in the district who accepted to participate as investigators, as well as
      five biology laboratories where DS screening was performed.

PMID- 14968022
TI  - [Perinatal drug abuse. Collaborative perinatal care for drug abusers and their
      infants].
AB  - Pregnant drug abusers are a group with very high risk of perinatal morbidity.
      Intensive prenatal care, with substitution maintenance programs, by a medico
      psycho-social team working in concert with ambulatory health and social workers,
      may prevent perinatal complications and mother-infant separation. The results of
      such a perinatal program, in a suburban low-socioeconomic population, are
      described. In comparison with reports in the literature, this approach appears to
      provide significant perinatal medical and social prognosis for pregnant abusers
      and their neonates.

PMID- 14968023
TI  - [Mid and long-term neurological prognosis of preterm infants less than 28 weeks
      gestational age].
AB  - The study of the long-term outcome of extremely premature babies is specially
      difficult because data in the literature is very heterogeneous. Recruitment
      (inborn, outborn), type of obstetrical management, and criteria and means used
      for interrupting curative treatment have varied greatly. We present the outcome
      of 204 infants born before 28 weeks of gestation between 1992 and 1997. The
      minimal follow up is 6 years. 82 infants (40.2%) died during the neonatal period.
      Significantly associated with neonatal death were absence of prenatal steroid
      course, male gender, elevated lactic acid at birth, and occurrence of pulmonary
      complications. When major neurological lesions (ventricular hemorrage stage III
      or IV and kryptic leucomalacia) developed, most infants died following a decision
      to stop active treatment. Out of the 114 survivors, 17 (14.9%) developed cerebral
      palsy (CP) or a low IQ. 31 (27.2%) had minor disorders, 66 (57.9%) were
      completely normal. The predictive factors of CP were major brain lesions,
      elevated lactic acid at the time of birth and multiple pregnancy. We also detail
      the minor neurological sequelae, cognitive behavioral, and psychological
      disorders observed in this population of extremely premature children and discuss
      the need for early and continuous care for these high risk babies.

PMID- 14968024
TI  - [Prenatal risk evaluation, parent information and mode of delivery].
AB  - Perinatal networks, antenatal administration of glucosteroids, postnatal
      administration of surfactant, and new techniques for mechanical ventilation, have
      considerably improved the prognosis of extremely preterm infants. Such recent
      progress in perinatology had enabled neonatologists to provide intensive care for
      infants born after 24 and 28 weeks of gestation. This practice raises serious
      medical and ethical issues. The optimal mode of delivery of such newborns is not
      well established mainly because available studies are retrospective and subjected
      to biases. Moreover, perinatologists are implicated in the continuing discussion
      on ethical issues that modify clinical practices.

PMID- 14968025
TI  - [Extremely preterm infants: resuscitation criteria in the delivery room and
      dialogue with parents before birth].
AB  - The resuscitation of extremely preterm infants presents complex medical, social
      and ethical issues for the families and the health professionals. The principle
      of a systematic resuscitation "temporary intensive care" does not prohibit the
      question of a limit in terms of gestational age and birth weight. In France, a do
      not resuscitate order (comfort care alone) is appropriate for newborns weighing
      less than 500g and/or with a gestational age of less than 24 weeks' since the
      mortality is nearly 100%. The survival of infants born at 24 weeks' gestational
      age remains low with significant risks of chronic medical problems and
      neurodevelopmental disabilities. The decisions regarding the extent of
      resuscitative efforts depend on antenatal factors, condition of the neonate at
      birth and the parental opinion. Before the delivery, parents should receive
      appropriate information about survival and risks of adverse long-term outcome.
      The physician should follow the parents' desires whenever the parents' decision
      would not obviously violate the infants' best interests. However, they must be
      informed that decisions about neonatal management made before the delivery can
      have to be changed in the delivery room, depending on the condition of the
      neonate at birth. At 25 weeks of gestational age, the prognosis is better and the
      resuscitation should be more intensive.

PMID- 14968026
TI  - [Risk of very preterm delivery: can we refrain from in utero transfer and manage
      these patients in level I and II maternity wards?].
AB  - The frequency of premature delivery is estimated at 0.5% of births (approximately
      2000 per year in France). The rate of in utero transfers before 28 weeks,
      although difficult to evaluate, is well above this percentage, raising the risk
      of overloading level III maternity wards. Who should or should not be
      transferred? What tests are most pertinent? What are the criteria for diagnosing
      premature labor? Which treatment should be offered? How should the decision to
      transfer be established? What information should be furnished to the parents? How
      should an unexpected delivery be managed? How should the transfer network be
      optimally organized?

PMID- 14968027
TI  - [Ethical dilemmas of extreme prematurity].
AB  - Caring for extremely premature babies is difficult and costly. Mortality has been
      reduced with recent medical progress, but at the price of an increased number of
      surviving infants with handicaps. Should we then fix firm limits (gestational age
      and/or birthweight) for deciding on whether or not to take medical action? There
      is however the question of whether it is ethically acceptable to define human
      life solely on the basis of the length of gestation or birthweight. Moreover,
      what risk level for death or handicap is legitimate for treating or not a
      premature baby? The issue thus comes to the worthiness of trying first to save
      life, then accepting an interruption of curative treatments later on if severe
      cerebral injuries become evident. Who should make the decisions? Guidelines have
      been published by medical associations to help professionals to answer these
      important and puzzling questions.

PMID- 14968028
TI  - [Evaluation of neonatal care discharge practices: three years experience].
AB  - OBJECTIVES: This study purpose was to identify the advantages and limitations of
      our practice in planning newborns' discharge from the neonatal unit. We searched
      for appropriate actions to promote good family conditions and environment for
      infants being discharged from the neonatal unit. MATERIALS AND METHODS: During a
      six-month period in 1999, we interviewed 110 families whose infants were
      discharged from our units. All interviews were conducted by the same person using
      a semi-directive protocol to collect the parents' perceptions of their child's
      hospitalisation and discharge and their recall of the first days at home. Data
      were collected after a sufficient period of adaptation at home. Analysis of the
      interviews showed that different difficulties could be prevented. Based on these
      findings, we instituted different pluridisciplinary discharge group to review
      practices in September 2000. In 2002, the same type of survey was conducted to
      evaluate improvement. RESULTS: Discharge from the neonatal unit was affected by
      the parents' perceptions of hospitalization, their ability to anticipate, before
      announcement of the "medical" discharge, home life with their child and to
      imagine their own professional and familial network. CONCLUSION: The parents'
      abilities to elaborate a discharge plan all along their child's hospitalisation
      helps improve the newborn's arrival in the family.

PMID- 14968029
TI  - [Role of pediatric medical home care].
AB  - According to the decree of 1992, the Paris hospitals (AP-HP) pediatric medical
      home care network offers care for all children irrespective of their pathology
      within the framework of a medico-psycho-social therapeutic project provided as an
      in alternative to traditional hospitalization. 30% of the admissions occur during
      the neonatal period. We studied the files of 249 newborn or preterm infants given
      in medical home care between January and September 2003. 71% were preterm
      infants. 46.4% of the children had been admitted at least once in an intensive
      care unit. At their admission in the pediatric medical home care unit, the median
      corrected gestational age was 39 weeks 6 days; 43% weighed less than 2500g, 9%
      less than 2000g, 22.5% of the preterm infants had a corrected gestational age
      less than 37 weeks, 65% of the infants presented gastrointestinal and/or feeding
      disorders. The average duration of stay in the pediatric medical home care unit
      was 20.5 days. The competence of pediatric nurses working in an integrated
      multidisciplinary team including psychologists and social workers is the key to
      success of pediatric medical home care.

PMID- 14968030
TI  - [Discharge of very preterm infants from neonatology: check list].
AB  - Key elements of the check list for neonatal discharge include: discharge
      discussion with parents, relation with maternal and child welfare assistants and
      family practitioner, scheduling of follow-up visits, request for insurance
      coverage, parental presence allowance, special education allowance, debriefing
      with nurses and nurses providers, clinical and biological appraisal, discharge
      prescription. For a former extremely premature baby, going home - often after a
      long hospitalization and a variety of pathologic problems - must be prepared and
      should not be decided in haste, not only for the baby and his/her parents, but
      also. for the neonatal staff!

PMID- 14968031
TI  - [Preventing dehydration with oral rehydration therapy (ORT) in less than 15-day
      old newborns: safety, efficiency and limits].
AB  - OBJECTIVES: We conducted a retrospective evaluation of enteral infusion with a
      marketed hypoosmolar oral rehydration solution (HORS), as an alternative to
      intravenous infusion. POPULATION AND METHODS: Premature infants, with difficult
      venous condition, 30 weeks or more during HORS infusion. Enteral ORS started
      after well-tolerated milk gastric gavage. Gradual increase of enteral feeding.
      RESULTS: January 1999 to April 2001, 105 neonates 28 weeks to 36 weeks, birth
      weight 1050 to 2700g, including 71.5% eutrophic newborns 30 to 34 weeks; 13.3%
      hypotrophic<10th P. More than 90% had a physiological weight curve: weight loss
      vs birth<15%, back to birth weight at day 15. No significant pathology during
      ORS. Failure of ORS for 7/105 children. Relative risk increased 8 fold if term
      was less than 30 weeks, 7 folds in the event of enteropathy before ORS. In 26.7%
      of the infants, gastric enteral residuals exceeded 1/3 of intake, vomiting and/or
      abdominal ballooning lasted less than 48 hours. There were 4 deaths during follow
      up (periventricular leucomalacia, myocardial infarctus) and 1 necrotizing
      enterocolitis. At theoretical birth date, 25% of the neonates were
      hypotrophic<10th P. At one and 2 years of age, less than 5% were still
      hypotrophic: relative risk increased 18 fold when birth weight was<5th P.
      CONCLUSION: HORS is an efficient, well-tolerated, low-cost and less invasive
      alternative to intravenous infusion. It must be reserved for eutrophic neonates
      born>30 weeks gestation due to risk of failure and insufficient growth.
      Validation with a multicentric clinical trial is in progress.

PMID- 14968032
TI  - [Enteral nutrition for the preterm infant: which maternal milk supplement?].
AB  - Different types of human milks are given to preterm newborns (mother and bank
      milk). Their effect on neonatal growth is recalled. The usefulness and
      justification of dietetic supplements as well as appropriate quantities and
      practical aspects are discussed.

PMID- 14968033
TI  - [Enteral nutrition: bolus versus continuous feeding].
AB  - Published evidence has not yielded clear guidelines about the best method of how
      to feed the preterm baby. Enteral feeding involves many potentially confounding
      interventions. Variations in nutritional practices are in part explained by
      difficulties in measuring outcome. Development and implementation of evidence
      based nutrition practices led to improved nutrition outcomes.

PMID- 14968034
TI  - [Trophic feeding and maturation of the gastrointestinal tract of the preterm
      infant].
AB  - Maturation of gastrointestinal function in neonates is stimulated by enteral
      nutrition whereas parenteral nutrition induces gastrointestinal atrophy and
      malfunction. Trophic feeding is the practice of feeding minute volumes of milk in
      order to stimulate the development of the immature gastrointestinal tract of the
      preterm infant. The provision of trophic feeding to the metabolically stable
      premature infant appears to result in multiple nutritional benefits and in
      minimum risk of complications. Further studies are, however, needed before
      recommending this practice routinely.

PMID- 14968036
TI  - [Implantation: the first maternal-embryo crosstalk].
AB  - Despite progress in assisted reproduction technologies, the lack of control of
      implantation remains a major obstacle to obtain successful pregnancies. It is of
      prime importance to determine the characteristic features of a receptive
      endometrium. Embryo implantation is a complex event involving apposition followed
      by the adhesion of the blastocyst to the maternal endometrium, and finally the
      invasion of this endometrium. Though implantation could occur in any human
      tissue, the endometrium is the only tissue where embryo implantation cannot occur
      except during a restricted period called the "implantation window". During this
      window, the endometrium is highly receptive to the embryo. Maternal-embryo
      crosstalk is favored by the implantation window. The molecular basis of the
      implantation window remains to be defined In the present study, we investigated
      the role of hCG, TGFbeta1, IGF1 and IGF2 in the secretion of leukemia inhibitory
      factor (LIF) and interleukin-6 (IL-6) by human epithelial endometrial cells in
      culture. Epithelial endometrial cells were obtained from endometrial biopsy in 28
      fertile women. HCG and TGFbeta1 added to primary cultures of human epithelial
      endometrial cells showed a stimulatory effect on LIF secretion and a reducing
      effect on IL-6 secretion. All these findings suggest a role for hCG and TGFbeta1
      in human embryo implantation.

PMID- 14968037
TI  - [The role of HLA-G expression in the embryo during implantation].
AB  - HLA-G is a non-classical major histocompatibility complex class I molecule, whose
      tissue distribution is mainly restricted to the placenta. HLA-G expression in the
      placenta is found mainly in extravillous cytotrophoblast that invades decidual
      tissue and maternal spiral arteries as well as villous cytotrophoblast (soluble
      form). Its function contributes to modulate local placental immunity during
      pregnancy: it is an immunosuppressive molecule inducing apoptosis of activated
      CD8(+) T cells and down-modulating CD4(+) T cell proliferation. HLA-G also
      modulates cytokine secretion of NK cells upon interaction with specific
      receptors. Soluble HLA-G1 may also contribute to the control of implantation.

PMID- 14968038
TI  - [Endometrial biopsy in the evaluation of endometrial receptivity].
AB  - The histological changes underwent by endometrium during a natural menstrual
      cycle were described more than 50 years ago. Dating yields several methodological
      flaws, with intra- and inter-observer variability and shows questionable
      relationship to endometrial receptivity. The best studied endometrial factors
      involved in implantation include the formation of luminal epithelial "pinopodes",
      expression of adhesion molecules and of cytokines. Ovarian stimulation for IVF is
      known to affect luteal phase function. Factors influencing the endometrial
      receptivity in such cycles are poorly understood. Studies comparing the
      endometrium in IVF cycles with natural cycle controls have shown premature
      secretory changes in the postovulatory and early luteal phase of IVF cycles.
      These findings suggest a profound modification of luteal endometrial development
      in stimulated cycles. Studies exploring the endometrium within the cycle of
      embryo transfer have shown a deleterious effect of severe periovulatory
      maturation advancement exceeding 3 days, as no clinical pregnancies were observed
      in this condition.

PMID- 14968039
TI  - [Three-dimensional ultrasonographic uterine vascularization and embryo
      implantation].
AB  - During the last decade transvaginal color Doppler has played an important role in
      increasing the understanding of early human development. Although our knowledge
      of early pregnancy development has recently improved, little is known about the
      most critical period of human development: implantation. Recent advances in three
      dimensional ultrasound have made studies of follicular development, ovulation and
      uterine receptivity more accurate. Three-dimensional ultrasound facilitates
      determination of the antral follicle number, ovarian volume calculation and
      analysis of the intensity of ovarian stromal blood flow in a short time without
      increasing the patient's discomfort. It is also possible to determine predictors
      of IVF outcome by three-dimensional ultrasound. Favorable ovarian stromal
      vascularity is associated with higher number of retrieved oocytes and increased
      pregnancy rates. The high degree of endometrial perfusion shown by color Doppler
      ultrasonography and on three-dimensional power Doppler histograms on the day of
      embryo transfer can indicate a more favorable endometrial milieu for successful
      in vitro fertilization. Uterine septum is the most common uterine abnormality
      occurring in infertile women. Three-dimensional ultrasound can be used as a
      screening method for detection of uterine abnormalities in patients suffering
      from infertility.

PMID- 14968040
TI  - [Prognostic factors of implantation].
AB  - One of the negative aspects of in vitro fertilization (IVF) and intracytoplasmic
      sperm injection (ICSI) is the increased risk of multiple pregnancies. There is an
      epidemic of twin pregnancies with a higher risk of obstetric, perinatal and
      neonatal complications than singleton pregnancies and with an important
      psychosocial, economic and financial impact for the parents to be. A reduction in
      the number of twins can only be obtained by the transfer of one embryo. Single
      embryo transfer with an acceptable pregnancy rate might be considered if a top
      quality embryo is available. The need to characterize embryos with optimal
      implantation potential is obvious. A top quality embryo is characterized by the
      presence of 4 or 5 blastomeres at day 2 and at least 7 blastomeres on day 3 after
      insemination, the absence of multinucleated blastomeres and<20% cellular
      fragments on day 2 and day 3 after fertilization. Others prognostic factors of
      implantation are discussed in this review. Judicious application of eSET can
      halve the twinning rate while maintaining the overall pregnancy rate.

PMID- 14968041
TI  - [Assisted hatching: procedure and effectiveness].
AB  - Assisted hatching (AH) has been proposed to improve the implantation rate in
      patients with poor prognosis for pregnancy. This systematic review of randomized
      controlled trials addresses primary outcomes of clinical pregnancy and embryo
      implantation. Several different methods for AH have been introduced over the
      years but comparative studies are lacking. AH using laser technology is probably
      the best technique. Assisted hatching increases the pregnancy and implantation
      rates significantly in patients with a poor prognosis undergoing IVF or ICSI,
      particularly in older women. More randomized trials are required to confirm any
      positive effects on the  take-home-baby rate  and to compare the different
      techniques.

PMID- 14968042
TI  - [Secreted cytokines in the uterine lumina are predictive of subsequent
      implantation. Presence of IL18 in the uterine flushing].
AB  - The materno-foetal relationship is not simply maternal tolerance of a foreign
      tissue, but a series of intricate mutual cytokine interactions governing
      selective immune regulation and also control of the adhesion and vascularisation
      processes during this dialogue. There is strong evidence that locally secreted
      cytokines, such as interleukine 18 (IL18) control the implantation process and
      can cause implantation failure in case of absence or overactivation. Uterine
      flushing fluids may be analysed to determine the level of several cytokines. At
      the time of egg retrieval, the flushing procedure does not adversely affect
      pregnancy rates. We report a strong positive correlation between the presence of
      IL18 in the uterine flushing and bad implantation rates. The presence of IL18 in
      the lumina is the traduction of an overactivation of endometrial IL18 that should
      be diagnosed and treated. Moreover, endometrial biopsy could define which type of
      cytokinic dysregulation is implicated in repeated implantation failure and define
      which type of treatment need to be introduced.

PMID- 14968043
TI  - [Natural cycle IVF (nIVF) in women with implantation failure].
AB  - Since the introduction of IVF treatments, natural cycle IVF (nIVF) has been
      largely replaced by IVF with ovarian stimulation to obtain multiple oocytes.
      Failure to anticipate the retrieval of more than two oocytes often results in
      cancellation of the cycle. However, nIVF has several advantages. It is associated
      with a close to zero multiple pregnancy rate, and a zero risk of ovarian
      hyperstimulation syndrome. Per cycle, nIVF is less time consuming, physically and
      emotionally less demanding for patients, and cheaper than stimulated IVF, but
      also less effective. GnRH antagonists have improved the outcome of nIVF cycles.
      They avoid unexpected ovulation and frequent cancellations. In selected cases,
      especially in women with implantation failure or with poor ovarian response,
      favorable results can be obtained from nIVF cycles, despite the replacement of a
      single embryo. Poor results are obtained in women over 38 years.

PMID- 14968044
TI  - [Impact of embryo transfer techniques on implantation rates].
AB  - Embryo transfer is an important step in the success of IVF treatment. All efforts
      should be made to avoid difficult embryo transfers provoking bleeding or uterine
      contractions. Evaluation before IVF treatment, including a trial transfer and a
      uterine ultrasonography, should allow one to evaluate the transfer step,
      anticipate problems, and thus improve treatment. An hysteroscopy can be useful
      for uterine cavity exploration. It is also important to remove cervical mucus
      before introduce the transfer catheter. It is essential to deposit embryos as
      gently as possible during IVF, avoiding manoeuvres that might trigger uterine
      contractions which could adversely affect the results of this treatment. Soft
      catheters perform better, and ultrasound-guidance facilitates embryo transfer.
      Progesterone administration starting on the day of oocyte retrieval induces a
      decrease in uterine contraction frequency on the day of ET (embryo transfer).
      Both Wallace and CDD catheters perform similarly. Trial catheterization on the
      day of ET could prevent most of the unanticipated procedural difficulties during
      the transfer.

PMID- 14968045
TI  - [Stress and embryo implantation].
AB  - Spontaneous abortion is the most common adverse pregnancy outcome, and stress has
      been suggested to be abortogenic in mice and humans. Stress-and/or pregnancy
      related hormones (corticotropin releasing hormone, adrenocorticotropin, and
      progesterone) might interact with peripheral and local immunocompetent cells,
      such as certain T cell, mast cells or NK cells, and result in changes of cytokine
      production. In an established murine model, abortions can be triggered by
      exposing the mice to stress during early gestation. Recent data from this model
      indicated that increased levels of abortogenic Th1 cytokines, a decrease of
      progesterone and thus, PIBP were incongruous with successful pregnancy
      maintenance. Supplementation of progesterone exerts a pregnancy protective effect
      by induction of a pregnancy-protective Th2 biased immune response. Interestingly,
      data from a prospective study on human pregnancy revealed that women with a
      clinically normally progressing pregnancy but low levels of progesterone during
      the first trimester eventually suffered from a miscarriage. These data indicate
      that stress may lead to increase abortions by altering the endocrine system,
      which triggers an immune bias towards an abortogenic cytokine profile.
      Progesterone may be a good marker to identify a putative thread of a miscarriage
      in human and progesterone replacement therapy may abrogate this thread by
      inducing a Th2 biased immune response from the decidua.

PMID- 14968046
TI  - [Psychological management of women with implantation failure].
AB  - Women who have been proposed to assess endometrial receptivity seem to be very
      interested in participating to this research. This biological re-start, when
      repeated failures contributes to self devalorization. Recent progresses in
      medical understanding of the physiology of implantation (endometrium cytokines)
      give a possible answer to the question of repeated implantation failures: men and
      women are able again to do something instead of being victims. Psychological
      management of the couples at this moment of medical investigation allows them to
      turn the repeated failures into a positive dynamic. This process is facilitated
      by the given possibility of a last attempt through a natural cycle.

PMID- 14968049
TI  - [Postoperative pain relief after gynecologic surgery].
AB  - Early administration of analgesics, generally before awakening from general
      anesthesia is useful to improve the patient's comfort in the post-anesthesia care
      unit (PACU). Multimodal analgesia includes administration of several analgesics
      from different pharmacological classes but in almost every combination, morphine
      or one of its derivatives is included. In the PACU, morphine is titrated using
      the intravenous route to obtain adequate and rapid pain relief. Analgesics are
      administered orally as soon as possible and in the vast majority of cases,
      immediate postoperative administration can be performed orally. After minor
      surgery (for example: diagnostic or operative laparoscopy) often performed in out
      patients, a combination of acetaminophen and of a non-steroidal anti-inflammatory
      drug with or without an oral preparation of morphine is efficient and safe.
      Intraperitoneal administration of a local anesthetic can be a useful addition.
      When the postoperative surgical stress is expected to be of moderate intensity
      (for example: hysterectomy), the same combinations can be used but are initially
      administered intravenously. Nefopam, which is available only by intravenous
      administration in France, can be safely added. Morphine is often applied using a
      patient-controlled analgesia device (PCA). After major surgery (especially after
      radical surgery for malignant disease), intrathecal or epidural analgesia, using
      a local anesthetic and an opioid is extremely efficient and is combined with
      other analgesics. Finally, because the affective dimension is extremely important
      after gynecologic surgery (especially in mutilating interventions), psychologic
      preparation, patient information and communication are essential components of
      care.

PMID- 14968050
TI  - [HTLV1 infection and pregnancy].
AB  - OBJECTIVE: We report an epidemiological study with an analysis of the risk
      factors of the HTLV-1 seroprevalence in pregnant women and their children in the
      town of St Laurent du Maroni, French Guyana. MATERIAL AND METHOD: HTLV-1
      seroprevalence and risk associated factors were first studied in all the pregnant
      women having delivered at St. Laurent between July 1991 and June 1993. Then, a
      retrospective analysis was performed in the children, aged between 18 months and
      12 years old, born from HTLV-1 infected mothers, focusing especially on the
      duration of breast feeding and the level of HTLV-1 anti body titers and proviral
      load. RESULTS: The global HTLV-1 seroprevalence was 4.4% (75/1727) but it was
      more prevalent among ethnic groups of African origin such as the Noir Marron
      population (5.5%) and Haitians (6.3%). In the Noir-Marron population, which
      represents 70% of the studied population, HTLV-1 seropositivity was associated
      with a maternal age of>35 years, prior miscarriage, prior cesarean section,
      parity>4, gravidity>6 and negative rhesus factor. After logistic regression, HTLV
      1 seropositivity remained associated with gravidity>6 and negative rhesus factor.
      Out of the 216 children born from 81 HTLV-1 infected mothers, only 21 were found
      to be HTLV-1 seropositive, giving a crude HTLV-1 transmission rate of 9.7% while
      among the 180 breast-fed children 10.6% were HTLV-1 seropositive. HTLV-1
      seropositivity in children was associated with elevated maternal anti HTLV-1
      antibody titer, high maternal HTLV-1 proviral load and child's gender, girls
      being more frequently HTLV-1 infected than boys. CONCLUSION: HTLV-1 infection,
      which can be responsible for severe pathologies in adults (adult T cell leukemia
      and tropical spastic paraparesis/HTLV-1 associated myelopathy) should be screened
      during pregnancy in women originating from high HTLV-1 endemic areas, as for
      France, mainly the French West Indies, French Guyana and Intertropical Africa. In
      case of HTLV-1 seropositivity, mothers should be informed on the risk of
      transmission and promotion of bottle feeding of their children should be strongly
      proposed.

PMID- 14968051
TI  - [Smoking and pregnancy: survey among women enrolled in an independent worker
      insurance program].
AB  - OBJECTIVES: In order to further improve its prevention program entitled
      "Maternity childhood follow-up", the Paris region health insurance program for
      independent workers carried out a survey among female participants. The survey
      was designed to assess women's smoking behavior and evaluate reception of
      information concerning smoking-related risks and support available to stop
      smoking. The women's suggestions were also collected. MATERIALS AND METHODS: A
      questionnaire was sent by the physicians in charge of the Ile de France region to
      the 3525 women who had reported a pregnancy. RESULTS: 1099 answers were received
      (31%) The mean age of responders was 34.3 4.7 years. Their educational level was
      high (76% had a university degree). Before pregnancy, 37% were smokers. At the
      first trimester of pregnancy, 17% were smokers, 15% at the second trimester and
      14% at the third trimester. Two years after childbirth, 20.5% were smokers. The
      proportion of women who stopped smoking was higher for those with a low
      Fagerstrom score. 29% of women said they did not receive any information about
      the harmful consequences of smoking. To cease smoking during pregnancy, 70% are
      helped by family and friends, 20% by health professionals; 3.5% took nicotine
      substitutes. CONCLUSION: This survey emphasises the need for improving
      information to pregnant women for alerting them to the dangers of smoking and for
      training the relevant health professionals.

PMID- 14968052
TI  - [Management of labor and delivery in low risk nulliparous women: comparison
      between level 1 and level 3 maternities].
AB  - OBJECTIVES: To compare obstetrical practices between level 1 ( community
      hospital) and level 3 (university hospital) maternities in a low risk nulliparous
      population. MATERIALS AND METHODS: 1532 low risk nulliparas were included in a
      retrospective study conducted in the setting of two maternities in the Ile-de
      France area. Cesarean delivery and forceps rates, management of labor, analgesia,
      maternal and neonatal outcomes were compared. RESULTS: Cesarean delivery rates
      were not significantly different (11.5% in level 3 vs 10.2% in level 1). Level 1
      maternity performed induction of labor more often (14.7% vs 8.7%, p<0.01).
      Peridural analgesia rates were higher in the level 3 maternity (95.1% vs 75.5%.
      p<0.01) but general anesthesia was two-fold more frequent in level 1 maternity.
      Level 3 maternity performed more instrumental deliveries (27.5% vs 17.4%, p<0.01)
      and more episiotomies (72.7% vs 39.3%). But we noted more first and second degree
      perineal tears in the level 1 maternity (29.9% vs 17.4%, p<0.01). Neonatal
      hospitalizations were more frequently in level 3 maternity. CONCLUSION: Some
      "interventionist" practices, but not all, were less frequent amongst physicians
      managing mainly low-risk women than amongst physicians managing mainly high-risk
      women but without difference for the cesarean delivery rates. The main
      differences were observed for epidural, instrumental delivery, and episiotomy
      rates but perineal tears and induction of labor were more frequent in the level I
      maternity. These differences could be explained by obstetrical politics in the
      two maternities rather than the type of level.

PMID- 14968053
TI  - [Teenage pregnancy and delivery: 276 cases observed at the Brazzaville University
      Hospital, Congo].
AB  - OBJECTIVE: To study sexuality, pregnancy and delivery in female teenagers.
      MATERIALS AND METHODS: Cross-sectional prospective study from January 1(st), 1997
      to May 31(st), 1998 concerning 276 female teenagers. The studied features were
      compared with a control group of 300 women aged more than 18 years chosen at
      random. RESULTS: Among 5204 women who delivered during the study period, 5.30%
      were teenagers. Their mean age was 14 years five months; 84.06% were single;
      2.90% were married and 13.04% were concubines. Analysis of social background
      showed that 41.66% had attended school, 51.10% had dropped out, and 7.24% were
      illiterate. Mean age at first sexual intercourse was 13 years 9 months. Only
      14.13% practised contraception, none used a condom. Mean term of the first
      prenatal consultation was 26 weeks gestation. Predominant pathological conditions
      observed during pregnancy were infections, anemia and complications of high blood
      pressure. Mean term at delivery (generally vaginal) was 38 weeks gestation. The
      rates of perinatal mortality and referral to the department of neonatology were
      higher than in the control population. CONCLUSION: Risk remains high for teenage
      pregnancy. Reduction of complication requires combined medical, psychological and
      social management.

PMID- 14968054
TI  - [Primary genital herpes with sacral meningoradiculitis].
AB  - Herpetic genital infection is a common sexually transmitted disease, caused in
      most cases by type 2 Herpes simplex virus (HSV2). This virus is characterized by
      its neurotropic properties and its ability to establish latency in sacral sensory
      ganglions. Some cases of genital primo-infection are complicated by viral
      replication dissemination to neigbhoring nerve structures like meninges and
      radicular terminations. In such cases muco-cutaneous manifestations are
      associated with peripheral neurological impairment in the form of meningo
      radiculitis. Physicians should be familiar with these neurological symptoms
      knowing that they always regress completely. The present report illustrates these
      complications and reviews the potential neurological implications described in
      the literature.

PMID- 14968055
TI  - [Lymphoepithelioma-like carcinoma of the uterine cervix: case report].
AB  - We report a case of a 79-year-old Tunisian woman who presented with post-coital
      bleeding. A polypoid mass of the cervix was discovered. Histopathological
      examination of the specimen biopsy showed a squamous-cell carcinoma. The patient
      underwent radical resection. The definitive diagnosis of lymphoepithelioma-like
      carcinoma of the cervix was retained after histopathological and
      immunohistochemical examination. There was no local involvement and no
      metastasis. The lymphoepitheloma-like carcinoma of the uterine cervix is a rare
      entity with distinct morphological features and a usually good prognosis.

PMID- 14968056
TI  - [Factors predictive of uterine rupture after operative hysteroscopy].
AB  - OBJECTIVES: To identify factors predictive of uterine rupture after operative
      hysteroscopy. When these factors are present, to search for means to prevent a
      later uterine rupture. Lastly to specify criteria allowing extraction of the
      fetus before rupture. PATIENTS AND METHODS: Dramatic description of a case of
      uterine rupture, in a patient who presented a history of uterine perforation
      secondary to operative hysteroscopy and retrospective analysis of 12 similar
      observations reported in the literature. RESULTS: Two types of situations must be
      differentiated: uncomplicated hysteroscopic resection of a polyp or sub-mucous
      fibroid does not seem to modify the obstetrical outcome; metroplasty for uterine
      malformation, complex synechia resections, and uterine perforations using
      monopolar current section are high-risk situations predictive of uterine rupture
      during pregnancy. CONCLUSION: Uterine ruptures secondary to operative
      hysteroscopy are rare but serious. They can occur before onset of labor, and
      compromise vital maternofetal outcome. Risk factors can be identified, but
      nothing can prevent natural history towards uterine rupture during pregnancy. The
      obstetrician's vigilance in this context must be extreme searching for the least
      clinical sign in favor of a pre-rupture of the uterus. Furthermore, systematic
      caesarean is not justified.

PMID- 14968059
TI  - [Proceedings of the 2nd Scientific Meeting on Infertility and Endometriosis. 13
      June 2003].

PMID- 14968061
TI  - [Physiopathology and therapeutic management of stage I and II endometriosis].
AB  - Stage I and II endometriosis is defined by a r-AFS score respectively ranging
      from 1 to 5 and from 6 to 15. This mild, superficial endometriosis is a very
      common pathology occurring in infertile women. Nevertheless, these women with
      stage I/II endometriosis have usually few pelvic pain. This review summarizes the
      recent literature concerning new data on the pathogenesis of peritoneal
      endometriosis and its clinical management. Retrograde menstruation, peritoneal
      adhesion of shed endometrial tissue, and outgrowth of endometrial cells, glands
      and stroma, are essential elements in the pathogenesis of endometriosis according
      to Sampson's classic implantation theory. Nevertheless, exact pathophysiology of
      endometriosis remains unknown. Superficial endometriotic lesions observed by
      laparoscopy have to be treated. Surgical procedure is not difficult for stage I
      and II of endometriosis. Surgical procedure remains controversial. Carbon dioxide
      (CO2) Laser can be used for laparoscopic destruction of endometriosis. Newer
      procedures, such as SurgiTouch (Lumenis), are more effective in vaporization and
      decrease the risk thermal damage of contiguous structures. The monopolar scissors
      can also be used in order to excise the peritoneal endometriotic lesions. Medical
      treatment may be usefull if surgical treatment is not complete or if the pelvic
      cavity is hypervascularized. In these cases, Gonadotropin-Releasing Hormone
      agonists (Gn-RHa) are the most common and effective treatment.;

PMID- 14968060
TI  - [Imaging features of endometriosis].
AB  - Deep pelvic endometriosis is responsible of a painful syndrome dominated by deep
      dyspareunia and pelvic pain that recur according to the menstrual cycle. The
      semiology is directly correlated with the location of the lesions but is not
      specific. It is essential to investigate (clinically and with magnetic resonance
      imaging (MRI)) these deep endometriosis lesions and to draw up a precise map,
      which is the only way to be sure that surgical excisions will be complete. For
      the diagnosis of deep endometriosis, MRI is more sensitive and specific than
      endovaginal ultrasonography. Bowel and utero-sacral ligament lesions are often
      underestimated by clinical examination and ultrasonography. The MR diagnosis of
      these deep lesions is also difficult and require adapted sequences but may vary
      following experience of the radiologist. Preoperative endorectal ultrasonography
      or MRI are reliable techniques to visualize perirectal endometriomas and to
      assess rectal wall involvement. Surgical management can be based on preoperative
      imaging diagnosis, the Bladder and ureteral lesions are also underestimated.
      Renal ultrasonography must be performed in women affected by severe deeply
      infiltrating endometriosis. MRI does not improve sensitivity nor specificity of
      the radiologic diagnosis of ovarian endometriomas. Nevertheless, MRI is a
      reliable technique to visualize deeply infiltrating endometriosis lesions
      associated with ovarian endometriomas.

PMID- 14968062
TI  - [Physiopathology, diagnosis and therapeutic management of stage III and IV
      endometriosis].
AB  - Stage III endometriosis is defined by a r-AFS score respectively ranging from 16
      to 40 and stage IV over 40. Deep pelvic endometriosis presents essentially in the
      form of a painful syndrome dominated by chronic pelvic painful, dysmenorrhea and
      deep dyspareunia. Pathophysiology of pelvic pain associated with endometriosis
      remains unknown. In the literature, correlation between extension of the
      endometriosis and severity of the painful remains controversies. Contraception by
      levonorgestrel-releasing intra-uterine systems appears to decrease pain related
      to deeply infiltrating endometriosis. Surgery by laparoscopy remains the first
      intention treatment when infertility is associated with endometriosis, whereas
      medical treatment is only palliative in the majority of cases. Success of
      treatment depends on how radical surgical exeresis is. Spontaneous pregnancy
      rates are significantly increased after surgical treatment. Recurrent ovarian
      surgery is not recommended in women with infertility, as it might be deleterious
      for ovarian reserve. Medical treatment using Gn-RH agonists is indicated when
      recurrence occurs after surgery.

PMID- 14968063
TI  - [Surgical treatment for endometriomas].
AB  - Endovaginal ultrasonography is relevant for the diagnosis of ovarian
      endometriomas with a good predictive value. Magnetic resonance imaging (MRI) may
      be recommended if deep endometriosis is suspected. Operative laparoscopic
      management is the 'gold standard' for surgical treatment, and medical treatment
      should not be given before surgery. Peritoneal lavage cytology must be performed
      before cystectomy. First, the cyst is opened and the endometriosic fluid is
      aspirated. The stripping technique is performed and after hemostasis, the ovarian
      cortex is reattached with microsurgical sutures. Coagulation or laser
      vaporization of endometriomas without excision of the pseudocapsule seems to be
      associated with a significant increase in risk of cyst recurrence. Recurrent
      ovarian surgery is not recommended in women with infertility, as it might be
      deleterious for ovarian reserve.

PMID- 14968064
TI  - [New concepts on pathophysiology, diagnosis and treatment of adenomyosis].
AB  - Adenomyosis is a relatively frequent disease, difficult to diagnose and which
      pathophysiology remains unknown. The treatment for the women which want to
      conserve or improve their fertility remains not well defined. Endovaginal
      ultrasonography seems to be as effective as MRI for the diagnosis of adenomyosis.
      Gn-RH agonist decreases symptoms and uterine volume; however, the symptoms
      reappear after discontinuation of agonist therapy, and side effects limit their
      prolonged use. Progesterone receptor modulators, anti-progestative and danazol or
      levonorgestrel-releasing intra-uterine system have been used as therapeutic
      modalities for adenomyosis, but the lack of controlled studies make their
      efficacy difficult to quantify. Some women with superficial adenomyosis may
      theoretically benefit from hysteroscopic myometrial or endometrial resection, but
      these procedures would be limited to women not wishing to conceive. Laparoscopic
      myometrial electrocoagulation or excision has proven to be effective but
      pregnancy following these techniques poses special problems, particularly the
      increased risk of uterine rupture. Transvaginal ultrasonography can successfully
      diagnose adenomyosis. Medical and conservative surgical treatments are already
      available.

PMID- 14968065
TI  - [Perspectives on endometriosis: new physiopathologic approaches and treatments].
AB  - Pathophysiology of deeply infiltrating endometriosis remains controversial
      whereas physiopathologic mechanism of superficial endometriosis is nearly
      demonstrated. Superficial peritoneal implants derive from adhesion and
      proliferation of endometrial cells regurgitated in peritoneum with retrograde
      menstruation. Peritoneal inflammation involving cytokines as TNFalpha and
      aromatase over-expression might be involved in the endometriosis invasion
      processus. Specific molecular defects of both eutopic and ectopic endometrium
      have been identified for each of the processes involved in the disease
      development. Aromatase inhibitors decrease endometriosis lesions in a mouse model
      of endometriosis which was induced surgically. Few studies report efficacy of
      aromatase inhibitors in human endometriosis. Theoretically, aromatase inhibitors
      should not be used alone in premenopausal women because of the resultant increase
      in gonadotropin levels. Nevertheless, in premenopausal women, aromatase
      inhibitors may be used in association with Gn-RH agonists. TNFalpha is a
      secretory factor of macrophages that is known to be increased in the peritoneal
      fluid of women with endometriosis. Granulosa cells from these women produce
      higher levels of TNFalpha. This cytokine can stimulate adhesion and proliferation
      of endometrial cells and enhances metalloproteasis expression, making thus
      endometrial cell invasion easier. It also stimulates angiogenesis by regulating
      expression of IL-8. TNFalpha is also cytotoxic to gametes. In mice and baboon
      models with induced endometriosis, anti-TNFalpha (TNF binding protein-1)
      decreases AFS score stage and reduces in size the endometriotic foci. No clinical
      assay has studied TNFalpha efficacy on human endometriosis.

PMID- 14968066
TI  - [Chronic pelvic pain and endometriosis].
AB  - Chronic pelvic pain and endometriosis remain two of the most perplexing problems
      in gynaecology. In some women, the problem is to determine whether or not
      endometriosis causes the pain they are consulting for. Deep pelvic endometriosis
      presents essentially in the form of a painful syndrome dominated by deep
      dyspareunia and painful functional symptoms that recur according to the menstrual
      cycle. The semiology is directly correlated with the location of the lesions
      (bladder, rectum). Lesions of the utero-sacral ligaments are the most frequent
      deeply infiltrating endometriosis lesions. The following variables are related to
      the severity of dysmenorrhoea: number of previous surgical procedures for
      endometriosis, score in the revised American Fertility Society classification,
      extensiveness of adnexal adhesion, Douglas obliteration, size of the posterior
      deeply infiltrating endometriosis implant, extent of the sub-peritoneal
      infiltration by the posterior deeply infiltrating endometriosis. It is essential
      to investigate (clinically and with magnetic resonance imaging) these deep
      endometriosis lesions and to draw up a precise map, which is the only way to be
      sure that exeresis will be complete. Surgery remains the first intention
      treatment, whereas medical treatment is only palliative in the majority of cases.
      Success of treatment depends on how radical surgical exeresis is. Operative
      laparoscopy is efficient for bladder, utero-sacral ligaments and vaginal deeply
      infiltrating endometriosis. However, indications for laparotomy still exist,
      notably for bowel lesions. Based on analysis of the anatomical distribution of
      deep pelvic endometriosis lesions, a "surgical classification" is proposed with
      the aim of establishing standard modes for surgical treatment. Further studies
      are required to clarify the place and modes for pre- and postoperative medical
      treatment.

PMID- 14968067
TI  - [Endometriomas and in vitro fertilization outcomes].
AB  - This paper reports the effects of endometrioma and their treatments on
      infertility out-come mainly in cases of in vitro fertilisation. This paper
      summarise a literature review and the experience of the Clermont-Ferrand
      infertility centre experience. The main conclusions are: the absence of any
      deleterious effects on IVF results in cases of endometriomas, the conservation of
      the oocytes stock in the ovary after any type of ovarian surgery for endometrioma
      (cystectomy or drainage plus laser vaporisation), the poor out-come of iterative
      surgical approach of endometrioma, the risk of ovarian abscess after puncture
      during an IVF procedure. From all these data the authors provides answers to the
      most frequent questions that arise in the cases of the presence of endometrioma
      in an infertile patient.

PMID- 14968068
TI  - [Ovarian stimulation regimens in women with endometriosis].
AB  - Controversies concerning the optimal treatment of endometriosis and its related
      infertility still exist, and few comparative studies are available. The number of
      oocytes retrieved and pregnancy rates seem to be higher after in vitro
      fertilization that follows long-term down-regulation with Gn-RH agonists, but the
      available studies are retrospective and do not allow definitive conclusion. No
      comparative studies are available between extra long and short Gn-RH agonist in
      women affected by endometriosis. No benefit of the use of danazol has been
      demonstrated in this indication. There are no data available on Gn-RH antagonist
      pretreatment before ovarian stimulation in patients with endometriosis undergoing
      assisted reproduction techniques. Endometrioma resection prior to IVF may
      compromise or destroy adjacent normal ovarian cortex and thus might reduce the
      ovarian reserve. Aspiration of endometrioma is associated with an increased risk
      of infection.

PMID- 14968069
TI  - [Results of IVF in women with endometriosis].
AB  - When associated with infertility, endometriosis often requires in vitro
      fertilization (IVF). The need of IVF instead of other Assisted Reproductive
      Technologies is correlated with the severity of the lesions and associated tubal
      pathology. Results of IVF (in terms of pregnancy rates), are influenced by the
      existence of endometriosis, but this influence remains controversial, and focused
      on three possible points: poor ovarian reserve (and ovarian response), poor
      quality of oocytes and embryos, poor implantation. It seems that mild and
      moderate endometriosis (I-II American Fertility Society score) has few
      deleterious effect on ovarian reserve, ovarian response, and pregnancy rates. All
      these parameters are decreased by the existence of severe endometriosis (III-IV
      AFS). Its surgical treatment appears to improve the results of IVF, notably in
      women under 35. But iterative surgery of endometriomas might be deleterious for
      ovarian function. Previous treatment by Gn-RH agonists also improves the outcome
      of IVF, whereas ICSI does not modify either the biological parameters, nor the
      pregnancy rates. Ovarian hyperstimulation in women with endometriosis might
      increase the severity of the lesions and the risk of complications: the use of
      unstimulated cycle (n-IVF) in young patients with normal ovarian reserve might be
      interesting.

PMID- 14968070
TI  - [Biological aspects of endometriosis in vitro fertilization].
AB  - Rinsing cumulus oophorus after oocyte retrieval is routinely performed in our
      department in Lyon for in vitro fertilization procedures when ovarian
      endometriosis is suspected. The aim of this procedure is to remove factors which
      might alter oocyte and embryo quality and fertilization and pregnancy rates.
      These factors, such as Tumor Necrosis Factor alpha (TNFalpha) and reactive oxygen
      species are known to be surexpressed in endometriosis. Their effect is not
      exclusively on the development of the oocyte and embryo but also on fertilization
      and implantation. It has been demonstrated that peritoneal and follicular fluid
      contains some factors that interfere with effective gamete interaction, as it has
      been determined by an in vitro animal assay. Peritoneal fluid from patients with
      mild endometriosis has an increased activity of TNFalpha, interleukin-1 (IL-1),
      antibodies and reactive oxygen species. This observation might be of importance
      in explaining subfertility associated with early stages of endometriosis. Cumulus
      oophorus rinsing after oocyte retrieval might help to remove these deleterious
      factors. IVF outcomes in women affecting by endometriosis seem to be similar
      after cumulus-oophorus rinsing, as compared to those of patients undergoing IVF
      for tubal-factor infertility. This rinsing procedure could also be usefull in
      women affected by unexplained infertility: peritoneal and follicular fluid of
      these women contains increased levels of TNFalpha and reactive oxygen species,
      like women affected by endometriosis.

PMID- 14968071
TI  - [Acute retinal necrosis: clinical presentation, treatment, and prognosis in a
      series of 22 patients].
AB  - PURPOSE: To evaluate the clinical outcome and medical management in a series of
      patients diagnosed with acute retinal necrosis. MATERIAL AND METHODS: Between
      1993 and 2000, 22 patients suffering from acute retinal necrosis were referred to
      our department. We retrospectively reviewed the clinical course, delay between
      diagnosis and first clinical manifestation, biological profiles, treatment and
      complications. RESULTS: All patients had vitreous inflammation; retinitis was
      seen upon examination in 82% of the cases. Nevertheless, for six patients (27% of
      the cases), failure to recognize the diagnosis led to delay (mean, 5.5 days)
      between the first ophthalmological examination and antiviral therapy. Nineteen
      patients underwent laboratory evaluation, and virological diagnosis was made in
      16 of them: varicella zoster virus was found in 11 cases, herpes simplex type 1
      in three cases, and herpes simplex type 2 and cytomegalovirus in one case each.
      Nine patients were treated with a combination of aciclovir and foscarnet and 13
      with aciclovir alone. Among the 16 patients who received aciclovir, one did not
      respond to therapy after 2 days and was cured only after foscarnet was added.
      Recurrence occurred at the end of treatment in only one patient. Retinal
      detachment complicated the course for 11 patients and was always associated with
      proliferative vitreoretinopathy. Among those, seven of the ten patients who
      accepted surgery were successfully treated. Eleven out of 22 patients had a final
      visual acuity up to 20/200 and two up to 20/40. CONCLUSION: In our series,
      acyclovir alone was sufficient to cure the majority of cases. Even with antiviral
      therapy, the prognosis of acute retinal necrosis remains poor. Retinal detachment
      is the main complication.

PMID- 14968072
TI  - [Simultaneous bilateral rhegmatogenous retinal detachment. 7 case studies].
AB  - PURPOSE: Simultaneous bilateral rhegmatogenous retinal detachments are rare. The
      purpose of our study was to examine the incidence, predictive factors, surgical
      results and prognosis of these retinal detachments. PATIENTS AND METHODS: A
      retrospective analysis of the medical records of 468 consecutive patients, 7-89
      years of age (mean, 45.7 years), undergoing surgery for rhegmatogenous retinal
      detachment between 1993 and 2000. RESULTS: During this period, a total of 497
      operations for rhegmatogenous retinal detachment were done. Thirty-two patients
      had bilateral rhegmatogenous retinal detachment. Simultaneous detachments were
      observed in seven patients (1.5%). In four cases, the diagnosis of retinal
      detachment was fortuitous. In fact, most patients presented with unilateral
      symptoms. The mean age (35 years) of patients suffering from simultaneous
      bilateral rhegmatogenous retinal detachment was younger than that of patients
      with unilateral or consecutive bilateral retinal detachments. Five patients were
      myopic. Multiple round retinal holes were the most frequent lesions responsible
      for retinal detachment. A preoperative proliferative vitreoretinopathy was found
      in 57% of cases. The retina was reattached in nine cases (81%). CONCLUSION:
      Simultaneous bilateral rhegmatogenous retinal detachment is usually found in
      relatively young myopic patients with atrophic retinal holes. They are rare but
      severe because of their frequent association with preoperative proliferative
      vitreoretinopathy.

PMID- 14968073
TI  - [A screening questionnaire for determining risk of Creuzfeldt-Jacob disease
      transmission during ophthalmic examination].
AB  - INTRODUCTION: The risk of prion transmission during an ophthalmic examination
      concerns all ophthalmologists screening patients at risk, a procedure normally
      based on collecting past history and clinical data. PATIENTS AND METHODS: The
      authors proposed a shortened version of a questionnaire where the patient
      provides only the past history by answering three questions, which are then
      validated by the ophthalmologist. RESULTS: This procedure was proposed to 500
      patients. Only five patients answered one of the questions positively, and the
      ophthalmologist did not use any contact device during their examination. Of these
      five patients, none was confirmed to be at risk for prion transmission.
      CONCLUSION: This questionnaire seems to be a suitable way to compensate the lack
      of time and reduced staff in ophthalmology, whatever the ophthalmic practice may
      be.

PMID- 14968074
TI  - [Early optic disc changes in open-angle glaucoma].
AB  - INTRODUCTION: Early diagnosis of chronic open-angle glaucoma is difficult: early
      changes in the optic disc often precede troubles in the field of vision, which
      occur gradually with no typical initial aspect. We report here the results of
      optic disc observations in normal subjects who became glaucomatous. OBSERVATIONS
      AND METHODS: A study was conducted on 64 eyes of 51 subjects followed on average
      over 12 years. At the start these eyes were normal or at risk for glaucoma for
      various reasons. Doubtful, difficult cases (severe myopia, dysversion or with
      associated pathology) were eliminated. Eventually, all the eyes presented open
      angle glaucoma. All patients underwent clinical and paraclinical examinations by
      the same examiner. The optic discs of 78 dilated eyes were examined with a slit
      lamp and a 78-dioptre lens and the results systematically tabulated. Of the 78
      optic discs, 40% had initial morphological characteristics (including cup/disc
      ratios) that were difficult to identify precisely. Preference was given to
      certain criteria that were easy to evaluate and likely to change. RESULTS: The
      classic aspects of glaucomatous papillary excavation appearance were observed.
      Forty-four discs showed notable changes (19 typical changes, 25 atypical), which
      were observed before visual field abnormalities. The size of the disc influences
      how the disease develops. Also noted were the frequency of changes in the slope
      of the papillary profile curve (third moment) and the frequency of changes in the
      quality of the papillary tissue, which takes on a translucent character locally.
      CONCLUSION: Documented and comparative observation of the optic disc remains a
      good and simple means for supervising subjects at risk for and in early diagnosis
      of chronic open-angle glaucoma. The evaluation of changes in the optic disc is
      greatly aided by the collection and the systematic recording of observations.

PMID- 14968075
TI  - [Phase 2 clinical study of 123I-N-(2-diethylaminoethyl)-2-iodobenzamide in the
      diagnostic of primary and metastatic ocular melanoma].
AB  - PURPOSE: Iodobenzamides are reported to possess an affinity for melanoma. A first
      selected compound, BZA, was studied in a phase 2 clinical trial on 159 patients
      as an imaging agent for the detection of primary melanoma and metastases with
      good results. We report the results of a second phase 2 clinical trial on 40
      patients with a new radiopharmaceutical BZA2 (an orthoiodinated BZA analog),
      which was expected to provide quality images sooner after injection and with
      better imaging contrast. PATIENTS AND METHODS: Performance was evaluated in 40
      patients classified with primary ocular lesions (12), suspicion of metastases of
      ocular or cutaneous origin (15), or with no known secondary lesion (13), and
      results were compared with conventional investigation techniques (ophthalmoscopy,
      ultrasonography, and angiography for ocular melanoma, whole-body CT scan and
      ultrasonography for metastases). RESULTS: No adverse events were recorded. The
      overall results on a per patient basis showed a sensitivity of 78% and a
      specificity of 95%. The four false negatives observed were ocular lesions (three
      with a thickness<3mm and one achromic), but all the proven secondary lesions were
      imaged. Moreover, negative BZA2 scintigraphy in cases of suspicious lesions led
      to the correction of two diagnoses: the prostatic origin of bone metastases and
      the endocrine tumor origin (APUD system) of an ocular lesion. DISCUSSION: BZA2
      scintigraphy is an easy test with good tolerance. In the diagnosis of ocular
      primary melanoma, the sensitivity of the test is 64%, although limited by the
      thickness (3mm) and the pigmentation of the lesion. However, the BZA2
      scintigraphy is a very useful test for the detection of melanoma metastases, with
      a sensitivity of 100% and a specificity of 95%. CONCLUSION: BZA2 scintigraphy
      showed good tolerance in patients and it appears promising for differential
      diagnosis, staging, and restaging of melanoma.

PMID- 14968076
TI  - [Ciliary body melanomas. Survival and prognostic aspects after brachytherapy or
      proton therapy].
AB  - INTRODUCTION: Our main goals were to study the survival of patients with uveal
      melanomas involving the ciliary body 5 and 10 years after treatment and to review
      prognosis. MATERIAL AND METHODS: This study investigated 106 tumors (27 ciliary
      body melanomas and 79 choroidal-ciliary melanomas) of patients treated between
      June 1983 and April 1998. Seventy-two patients were treated with 106-ruthenium
      applicators and 34 were treated with proton therapy. Some large tumors or
      recurrences required a second treatment. The mean follow-up period was 91 months.
      RESULTS: The mean tumor sizes before treatment were 6,6mm for melanoma thickness
      and 10.3mm for mean largest basal melanoma diameters (LTD). Of the patients
      studied, 71% were still alive at 5 years, 35% had metastasis and 27.7% developed
      recurrences. Multivariate analysis showed that the risk factors for melanoma
      related death were LTD greater than 13mm, presence of exudative retinal
      detachment, macroscopic iris root involvement at the time of diagnosis, and
      choroidal-ciliary location. DISCUSSION AND CONCLUSION: With 71% of patients still
      alive at 5 years, this review shows that melanomas involving the ciliary body do
      not seem less severe than more posterior uveal tumors. Because of size
      differences between ciliary body melanomas and choroidal-ciliary melanomas, we
      cannot come to the conclusion that choroidal-ciliary melanomas have a poorer
      prognosis than ciliary body melanomas. Largest tumor diameter over 13mm, presence
      of exudative retinal detachment, and macroscopic iris root involvement at the
      time of diagnosis are important risk factors for melanoma-related death, as shown
      by the multivariate analysis.

PMID- 14968077
TI  - [Combined hamartoma of the retina and retinal pigment epithelium].
AB  - We report the case of a 31-year-old man who developed a combined hamartoma of the
      retina and retinal pigment epithelium in the left eye. The diagnosis was
      determined based on alterations discovered on fundus examination: hyperplasia of
      the retinal pigment epithelium cells and tortuosity of the vessels and glial
      epiretinal membrane. These modifications made it possible to differentiate the
      hamartoma from choroidal melanoma. The patient underwent photocoagulation
      therapy. His death due to stroke 4 years after therapy made it possible to
      analyze the eyeball. Histopathological examination revealed alterations due to
      retinal photocoagulation as well as alterations particular to the primary tumor:
      hypertrophy of the retinal pigment epithelium and glial and vascular overgrowth.

PMID- 14968078
TI  - [Leber's optic neuropathy presenting as an alcohol- and tobacco-related optic
      neuropathy].
AB  - The authors report a case of a 70-year-old man presenting a recent unilateral
      decrease in visual acuity, appearing in a context of alcohol and tobacco
      intoxication. Diagnosis of Leber's optic neuropathy was evoked after elimination
      of other causes of a visual acuity decrease such as giant cell arteritis and
      compressive or inflammatory optic neuropathy. The authors emphasize that Leber's
      optic neuropathy must be evoked in a recent decrease in visual acuity, even if it
      appears in an unusual context.

PMID- 14968079
TI  - [An atypical case of malignant hypertensive retinopathy in a young child].
AB  - Stage IV hypertensive retinopathies in children have been described, but their
      incidence appears to be rare. Most etiologies are nephropathies. The authors
      present a clinical case of malignant high blood pressure in a young girl whose
      ophthalmological tests detected an unusual nephropathy, the Ask-Upmark kidney,
      illustrating the importance of determining high blood pressure chronicity and
      using Kirkendall's classification. Systematic fluorescein angiography and NMR on
      atypical subjects prevents the diagnosis of Leber neuroretinis, the main
      differential diagnosis. Early treatment of high blood pressure can avoid
      complications such as macular exudes.

PMID- 14968080
TI  - [Retinal hemorrhages after ivermectin treatment for onchocerciasis in a patient
      with Loa loa microfilaremia].
AB  - A case of retinal hemorrhages with special features and degradation of the
      general condition is reported in a 27-year-old female patient, following the
      ingestion of ivermectin for the treatment of onchocerciasis. The patient was
      infested by both Onchocerca volvulus and Loa loa. A bilateral peripheral temporal
      location of the retinal lesions was observed. The role of L. loa microfilarial
      load in the occurrence of the retinal lesions as well as the transient character
      of the lesions are discussed, based on the clinical observation and with
      reference to the literature. The authors call for setting up a rapid therapeutic
      system to take care of serious adverse reactions following treatment with
      ivermectin in areas with a high prevalence of L. loa infestation.

PMID- 14968081
TI  - [Orbital extension of sinus plasmacytoma secondarily transforming into multiple
      myeloma: a case study].
AB  - We report the case of a 39-year-old man who consulted for severe exophthalmia
      with diplopia associated with chronic sinusitis evolving over 6 months. A
      cervicofacial CT scan showed a tumoral mass invading the maxillary and ethmoidal
      left sinus and orbital cavity. A biopsy of the mass and general evaluation
      confirmed the diagnosis of extramedullary plasmocytoma. Secondarily it
      transformed into multiple myeloma. In light of this case of extramedullary
      plasmocytoma in a young subject, we discuss the clinical characteristics,
      ophthalmologic manifestations, and the various therapeutic modalities according
      to the stage of the disease and the ocular repercussions.

PMID- 14968082
TI  - [Photodynamic therapy. Foreword ].

PMID- 14968083
TI  - On the selectivity of photodynamic therapy of choroidal neovascularization
      associated with age-related macular degeneration.
AB  - PURPOSE: This paper discusses the lack of complete selectivity in the
      photodynamic closure of choroidal neovasculature (CNV) associated with age
      related macular degeneration. The arguments presented are supported by examples
      of clinical observations and may be useful for the design of the next generation
      of photosensitizers. RESULTS AND CONCLUSION: Based on worldwide patient follow
      up, it can be concluded that a substantial number of the more than 200000
      treatments that have been dispensed so far could have resulted in stabilization
      of the disease for at least a number of years. Clinical observations also
      indicate that, in addition to the effective closure of the CNV observed 1 week
      after PDT, a significant closure (or at least reduced leakage) of normal
      choriocapillaries is observed in the treated area. Some of the concepts
      associated with the selectivity of Visudyne photodynamic therapy of choroidal
      neovascularization in age-related macular degeneration are also discussed.
      DISCUSSION: Novel approaches to improving selectivity could include attaching a
      photosensitizer to a targeting moiety such as a monoclonal antibody or a peptide.
      The undesirable closure of normal choriocapillaries in the treated area is one
      area of possible improvement to be sought for the next generation of drugs.

PMID- 14968084
TI  - [Indications for photodynamic therapy in age-related macular degeneration].
AB  - Exudative age-related macular degeneration (ARMD) is now benefitting from new
      therapeutic approaches. Three international randomized clinical trials have
      demonstrated the efficacy of photodynamic therapy (PDT) in stabilizing visual
      acuity at 2 years. PDT is based on the activation of a photosensitizer with an
      adapted wavelength. In age-related macular degeneration, the photosensitizer used
      is verteporfin (Visudyne), which accumulates preferentially in choroidal new
      vessels. Functional results are obtained on the basis of a strict classification
      based on fluorescein angiography examining the type of the new vessels
      responsible for exudative ARMD. Thus, subfoveal lesions, either predominantly
      classic (>50%) or occult only, are the indication for PDT. Classic CNVs where
      laser photocoagulation thermal burns extend into the foveola may be an
      extrapolation of the indication for PDT. In addition, fluorescein angiography is
      essential for considering retreatment, usually necessary. Demonstrated growth and
      the persistence of leakage from the CNV is an absolute indication for a new
      session of PDT. A number of features still require assessment in order to define
      the responder group more accurately and to refine and possibly simplify the
      indications for retreatment.

PMID- 14968085
TI  - [Monitoring the patient after treatment: angiographic aspects of recurrence and
      indications for retreatment].
AB  - OBJECTIVES: Dynamic phototherapy with intravenous injection of Verteporfin
      (Visudyne) is a relatively recent therapeutic concept based on a photochemical
      reaction. Its statistically significant efficacy has been demonstrated in
      treating choroidal newvessels and age-related macular degeneration. This
      occlusion is often temporary, thus requiring repeated treatments in persistent
      cases and/or recurrences. Angiographic monitoring of the patient, over the short
      or medium term and then later over the long term, will identify these cases.
      METHODS: The indications for retreatment are based on very close follow-up with
      fluorescein angiographic results, and the persistence or reappearance of leakage
      should be analyzed and clearly distinguished from staining phenomena. Leakage is
      an essential element and the main diagnostic criterion of recurrence. Associated
      criteria could be envisaged based on follow-up angiographic examinations at
      different stages of progression: early, at 4 or 6 weeks (often a good indicator
      of progression), or at 3 months, currently indispensable. RESULTS: With a
      relatively stable lesion with no progression or extension, the angiographic
      examination will make it possible to decide whether a treatment is needed: either
      retreatment if there is leakage or no treatment if the lesion is fibrous. To
      assist in therapeutic decisions, a number of arguments must be gathered based on
      fluorescein angiography but also on indocyanine green angiography (ICG), which
      will analyze neovascularization, and optical coherence tomography (OCT)
      examination, which will bring out the presence or absence of fluid at the lesion,
      as well as functional signs of visual acuity. In difficult cases, the
      angiographic examination will determine the source of the major decreases in
      acuity that can be caused by hemorrhages, breaks (which are not necessarily
      absolute contraindications for retreatment), or acute choroidal ischemia.
      CONCLUSIONS: Fluorescein and IGC angiographic follow-up and OCT examinations will
      screen and analyze persistence or reperfusion of choroidal neovessels as well as
      the extension or reappearance of lesions and, on the other hand, the presence or
      absence of fibrotic staining phenomena and scarring. The changes in central
      visual acuity and different functional signs are indicators of patient management
      and therapeutic indications.

PMID- 14968086
TI  - [Visudyne photodynamic therapy and feeder vessel occlusion: rationale of a
      synergistic association and clinical options].
AB  - PURPOSE: Visudyne photodynamic therapy (PDT) has provided considerable
      improvement in patient care of subfoveal choroidal neovascularization (CNV).
      Patients tend to loose vision for a few months after the initial treatment, but
      the 4-year proven stability in vision most often provides an acceptable quality
      of life, sometimes with additional low vision rehabilitation. The initial visual
      acuity loss, borderline cost-effectiveness, and subgroups of patients not
      responding to PDT warrant improving the symptomatic treatment of subfoveal CNV.
      Today, the most tempting solution would be to combine PDT with an occlusion of
      the feeder vessel (FV). METHODS: Two patients are described in whom the feeder
      vessel was occluded using modifications of the classic PDT treatment method. The
      FV was identified in both patients using fluorescein and indocyanine green
      angiographies at a recorded video rate using a modified scanning laser
      ophthalmoscope (Rodenstock SLO). The feeder vessel of the first patient was
      occluded by minimal photocoagulation immediately after a Visudyne PDT treatment
      in order to take advantage of the reduced blood flow within the feeder vessel.
      The second patient presenting a subfoveal FV was treated using a modified PDT
      treatment called feeder-vessel PDT. The photosensitizing agent was activated by a
      first classic spot covering the lesion, followed immediately by a small spot
      focused on the feeder vessel. RESULTS: Both subfoveal CNVs were successfully and
      selectively occluded and some visual acuity was gained following the treatment.
      CONCLUSION: Occlusion of the feeder vessel is an appealing clinical option that
      is complementary to Visudyne PDT. Both treatment methods presented here could
      provide additional options to close subfoveal CNV with an optimal efficacy-risk
      ratio.

PMID- 14968088
TI  - [Ultrabiomicroscopy and glaucoma].

PMID- 14968089
TI  - [Palpebral edema secondary to treatment by a specific inhibitor of tyrosine
      kinase: Glivec. A case report].
AB  - Iatrogenic causes for palpebral edema are rarely suspected and must be
      specifically sought. The authors report a case of palpebral edema in a patient
      treated with a specific inhibitor of the BCR-ABL tyrosine kinase (Glivec) for
      chronic myeloid leukemia. Histopathological analysis of specimens of the excised
      upper eyelid tissue revealed the absence of leukemic infiltration, suggesting the
      toxic effect of the treatment. This side effect should be noted so that patients
      are informed and biopsy is proposed to eliminate tumoral infiltration.

PMID- 14968092
TI  - [Mission odontology].

PMID- 14968093
TI  - [Our point!].

PMID- 14968094
TI  - [Total osteotomy for maxillary setback. Indications, technique, results].
AB  - PURPOSE: Maxillary skeletal protrusion used to be treated by orthodontic
      treatment or combined surgical and orthodontic treatment consisting in extraction
      of two maxillary premolars associated with anterior maxillary osteotomy. Although
      the anterior occlusal result is quite often good, the esthetic impact is often
      unsatisfactory. Furthermore, these methods do not correct for the generally
      associated vertical maxillary excess nor for the first molar class II relation.
      MATERIAL AND METHODS: This retrospective study included 11 patients who underwent
      posterior repositioning of the maxilla between 1986 and 2001. The indication for
      surgery was based on clinical and cephalometric criteria as exposed. Patient
      evaluation was based on bony stability and relation between hard and soft tissue
      changes, and changes in hard and soft tissues cephalometric landmarks assessed
      prior to surgery, post operatively and six months post operatively. RESULTS:
      Results were considered quite good with restoration of a first molar Class I
      relation, restitution of facial harmony and an esthetic soft tissue profile.
      Cutaneous movements after surgery, the relation between hard and soft tissue
      changes and rate of relapse are reported. DISCUSSION: We compared our series with
      those reported in the literature emphasizing diagnostic and technical
      difficulties. This method, which provides good healing as well as the good
      stability can be recommended for surgical treatment of patients with maxillary
      protrusion associated with vertical maxillary excess.

PMID- 14968095
TI  - [Results of an evaluation of clinical practice in orthognathic surgery in France
      in 2002].
AB  - BACKGROUND: Over the years, orthognathic surgery has become a mainstay of
      maxillofacial surgery and is the object of many publications and oral
      communications. However, in spite of well-established methodology, disparities
      still exist in France basically concerning the way orthognathic surgery is
      performed. MATERIALS AND METHODS: In relation with the XXXIXth congress of
      Stomatology and Maxillofacial surgery, a questionnaire was mailed to 100 French
      maxillofacial surgeons. Questions dealing with some practical points of
      orthognathic surgery (condylar positioning, osteosynthesis technique, rate of
      condylar resorption.) were asked. RESULTS: Overall reply rate was 37%. Condylar
      positioning was performed empirically in 73% of the cases. Mandibular
      osteosynthesis was achieved by titanium miniplates alone in 70%. Post-operative
      condylar resorption rate was about 2%. This survey produced numerous astute
      comments. DISCUSSION: This survey highlighted the interest of maxillofacial
      surgeons for practical aspects of orthognathic surgery including the questions of
      condylar positioning or osteosynthesis technique. These points are instrumental
      in achieving high-quality surgical result.

PMID- 14968096
TI  - [Anatomic facial and behavioral features of Australopithecus africanus. Apropos
      of the Taung child].
AB  - INTRODUCTION: Taung's skull was first Australopithecus described. The initial
      description did not mentioned premaxillary bone (os incisivum). MATERIALS AND
      METHODS: Photographs of Taung's skull were studied to investigate the presence of
      a suture between a maxillary bone and a premaxillary bone. These photographs were
      compared to a dissected macaca's head and earlier publications. RESULTS: A suture
      is clearly visible on the anterior aspect of the face of Taung's skull as it is
      on the non-human primate face. DISCUSSION: Among the anatomic features of
      Australopithecus africanus, some are humanoid (the cranium is over the face),
      others are anthropoid (presence of a separate premaxilla, presence of a supra
      orbital torus, absence of a mental prominence). Unlike homo individuals, there is
      no proof Australopithecus africanus made tools. The definition of Man is not an
      anatomic definition but rather a socio-cultural definition.

PMID- 14968097
TI  - [Superficial vascular anomalies of the face: apropos of six cases].
AB  - The classification of superficial vascular anomalies of the face recognizes two
      major categories: hemangiomas and vascular malformations. A multidisciplinary
      approach to these malformations is necessary. MRI of venous vascular
      malformations, pulsed Doppler and arteriography of arteriovenous malformations
      are key examinations in the exploration strategy for superficial vascular
      malformations. Hemangiomas always regress. Surgery is generally needed only for
      late sequelae although in some cases early surgery is beneficial. Percutaneous
      sclerotherapy and surgery are indicated for venous malformations in order to
      minimize or improve skin, muscle and bone distorsions. Arteriovenous
      malformations are the most dangerous vascular anomalies of the face.
      Superselective arterial embolization prepares the surgical excision of the nidus,
      complete resection is essential. We review 6 cases of superficial vascular
      malformations of the face treated surgically and discuss the diagnosis features
      and the treatment modalities of these vascular anomalies.

PMID- 14968098
TI  - [Coronal approach. Surgical technique].
AB  - Many indications in maxillo-facial surgery require a coronal approach. We recall
      the main anatomic features and describe the surgical technique.

PMID- 14968099
TI  - [Non-Hodgkin lymphoma of the infratemporalis fossa: a case report].
AB  - Extranodal non-Hodgkin lymphoma of the head and neck is usually seen in the
      Waldeyer's ring. Localizations in the infratemporalis fossa are rare and to date,
      only seven cases have been reported. The clinical and radiographic features of
      non-Hodgkin lymphoma is non-specific. Positive diagnosis requires a pathologic
      examination, generally guided by immunohistochemistry results. We report a case
      and discuss the epidemiological, diagnostic, therapeutic and prognostic features
      of these tumors.

PMID- 14968100
TI  - [Ectopic tooth in the nasal cavity].
AB  - The eruption of a canine tooth into the nasal cavity constitutes one topographic
      form of dental ectopy. We report a case and discuss the diagnostic aspects and
      diverse pathogenic theories proposed. This unusual situation should be suspected
      in patients with nasal obstruction and unilateral fetid purulent rhinorrhea.

PMID- 14968101
TI  - ["http://stomatonantes.free.fr", the Internet web site of th Stomatology and
      Maxillofacial Surgery Service of Nantes, after one year].

PMID- 14968102
TI  - Microvascular instability in tetraplegic patients: preliminary observations.
AB  - STUDY DESIGN: Case control. OBJECTIVES: To describe the effect of spinal cord
      injury on microvascular stability. SETTING: Veterans Administration Medical
      Center, West Roxbury, MA, USA. METHODS: A total of 19 tetraplegic patients, aged
      63+/-12 years, were surveyed for microvascular instability. Photoelectric pulse
      sensors were applied to the skin surface of the neck on both sides and to the
      distal pads of the left and right fourth fingers of subjects in the sitting
      position. All pulses during the survey periods were recorded by a polygraph
      system. The unstable fraction of pulsatile cutaneous blood flow (UFCF) was
      calculated by the sum of the periods during which pulses at any site were either
      half or twice the baseline amplitude divided by the survey time. Simultaneous
      UFCF, which was pulsatile flow change in the same direction at the same time in
      two leads, was also measured. Flow changes in patients with motor and sensory
      complete lesions were compared with incomplete lesions. RESULTS: Survey times
      were 7017+/-670 s. Tetraplegic complete UFCF and simultaneous UFCF were 0.25+/
      0.12 and 0.07+/-0.07, respectively. Tetraplegic incomplete UFCF and simultaneous
      UFCF were 0.0.13+/-0.9 and 0.02+/-0.04, respectively. The differences between the
      groups were significant for UFCF (P=0.04), but not for simultaneous UFCF
      (P=0.14). CONCLUSIONS: Tetraplegic subjects demonstrate an instability of
      cutaneous microvascular blood flow that is related to the severity of paralysis.

PMID- 14968103
TI  - Temporal differences in relative phasing of gait initiation and first step length
      in patients with cervical and lumbosacral spinal cord injuries.
AB  - STUDY DESIGN: Comparison group design. OBJECTIVE: To compare the temporal
      distance factors during gait initiation between patients with incomplete cervical
      spinal cord injury, incomplete lumbosacral spinal lesion, and unimpaired control
      adults. SETTING: Human performance and movement analysis laboratory, Taiwan.
      PARTICIPANTS: Five patients with an incomplete cervical spinal cord injury (Group
      1), five patients with an incomplete lumbosacral spinal lesion (Group 2) and nine
      unimpaired control adults (Group 3). METHODS: Subjects underwent a three
      dimensional gait analysis. The total gait initiation period, reaction time, each
      relative phasing of gait initiation and the length of the first step were
      identified by using the kinematic measurement system. MAIN OUTCOME MEASURES: The
      total gait initiation period (start of the auditory cue for gait initiation to
      heel-strike of the first swing leg); each relative phasing of gait initiation
      indicated that the duration of the preparatory phase (start of auditory cue for
      gait initiation to heel-off of the first swing leg), the duration of the push-up
      phase (heel-off to toe-off of the first swing leg), and the duration of the
      single-stance phase (toe-off to heel-strike of the first swing leg) established
      by the total gait initiation period; and the length of the first step. RESULTS:
      The gait initiation period was greater in Groups 1 and 2 than that of Group 3
      (P<0.05). Each relative phasing including the duration of the preparatory phase,
      the push-up phase, and the swing phase relative to the total gait initiation
      period, did not differ among Groups 1-3 (P>0.05). The length of the first step,
      measured while the nonpreferred leg stepped first in Groups 1 and 2, was shorter
      than that of Group 3 (P<0.05). CONCLUSIONS: Patients with incomplete cervical
      spinal cord injuries or lumbosacral spinal lesions took more time in gait
      initiation than unimpaired control adults. The first step length also reduced in
      these patients while the nonpreferred leg stepped first, as compared to
      unimpaired control adults. The data indicated that centrally programmed gait
      initiation might be preserved in ASIA-D spinal patients who, in this study,
      executed gait initiation with varying temporal distance strategies to compensate
      for peripheral impairments, as compared to unimpaired control adults.

PMID- 14968104
TI  - Length of stay in hospital following spinal cord lesions in Israel.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To monitor length of stay
      (LOS) in a specialist spinal cord lesion (SCL) department in Israel, evaluate
      factors that affect it, and assess its association with other outcome measures.
      SETTING: Loewenstein Rehabilitation Hospital, Raanana, Israel. METHODS: In all,
      1367 SCL patients treated between 1962 and 2000, and a group of 44 patients
      admitted between 1996 and 2002 were recruited. LOS, factors that affect it, and
      Spinal Cord Independence Measure second version (SCIM-II) gain and efficiency
      were measured. Data were collected from hospital charts and from the Population
      Registry of the Israel Ministry of Internal Affairs. LOS associations were
      analyzed with ANOVA, ANCOVA, Pearson's chi(2) test, Pearson's correlation, and
      Cox proportional hazard model. RESULTS: The mean LOS was 239 days for traumatic
      SCL (SD=168) and 106 days for non-traumatic SCL (SD=137). SCL etiology, SCL
      severity, and decade of admission to rehabilitation, were associated with the LOS
      (P<0.001). SCIM II gain correlated with LOS in the first 70 days after admission
      (r=0.81-0.82; P<0.001). In some patients, longer LOS was associated with a
      considerable increase in ability, through 5-8 months from admission. CONCLUSIONS:
      LOS of patients with SCL in Israel is within the customary LOS range in Europe.
      Longer LOS in a specialist SCL department may be positively associated with
      improved rehabilitation outcome. Further study is required to determine the LOS
      that allows optimal achievements.

PMID- 14968105
TI  - Spinal subdural haematoma: how relevant is the INR?
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report a rare cause of spinal cord
      compression. SETTING: University Hospital, Wales, UK. CASE REPORT: A 67-year-old
      gentleman on oral anticoagulation for atrial fibrillation presented with a 4-h
      history of progressive loss of sensation and weakness in both legs; there was no
      history of trauma. On examination, he had a flaccid paraplegia with altered
      sensation in the L1,2,3 dermatomes and complete anaesthesia in the L4,5
      distribution. Knee and ankle jerk reflexes were absent, plantars were equivocal
      and anal sphincter tone was reduced. The patient's international normalized ratio
      (INR) was 4.1. An MR scan showed an extensive intradural haematoma compressing
      the cauda equina. The anticoagulation was reversed and an urgent T12-L2
      laminectomy was performed; findings were a circumferential haematoma at L1
      extending in the anterior canal between T10 and L3. The patient had an uneventful
      postoperative course generally, but at 1 week there was no neurological recovery.
      CONCLUSION: This case highlights that anticoagulation even when well controlled
      is not without risk. This is particularly of concern as the number of patients
      receiving long-term anticoagulation therapy has doubled between 1993 and 1998.

PMID- 14968106
TI  - Neurological improvement and rehabilitation potential following toxic myelopathy
      due to intrathecal injection of doxorubicin.
AB  - STUDY DESIGN: Case report of a 31-year-old woman who presented with toxic
      myelopathy due to intrathecal administration of doxorubicin. OBJECTIVE: To
      describe the pathology and the rehabilitation of an uncommon complication of
      intrathecal drug administration during the oncologic treatment of acute lymphoma.
      SETTING: Spinal cord rehabilitation center, University Hospital. METHOD: Clinical
      and radiological observations during a rehabilitation program. RESULTS: Evidence
      of neurological improvement and rehabilitation potential after severe myelopathy
      due to intrathecal injection of doxorubicin. CONCLUSION: This is, to our
      knowledge, the first report of severe myelopathy following accidental intrathecal
      administration of doxorubicin. Despite early complete paraplegia, some
      neurological and functional recovery was observed.

PMID- 14968107
TI  - Towards improved clinical and physiological assessments of recovery in spinal
      cord injury: a clinical initiative.
AB  - Clinical practice and scientific research may soon lead to treatments designed to
      repair spinal cord injury. Repair is likely to be partial in the first trials,
      extending only one or two segments below the original injury. Furthermore,
      treatments that are becoming available are likely to be applied to the thoracic
      spinal cord to minimise loss of function resulting from damage to surviving
      connections. These provisos have prompted research into the improvement of
      clinical and physiological tests designed (1) to determine the level and density
      of a spinal cord injury, (2) to provide reliable monitoring of recovery over one
      or two spinal cord segments, and (3) to provide indices of function provided by
      thoracic spinal root innervation, presently largely ignored in assessment of
      spinal cord injury. This article reviews progress of the Clinical Initiative,
      sponsored by the International Spinal Research Trust, to advance the clinical and
      physiological tests of sensory, motor and autonomic function needed to achieve
      these aims.

PMID- 14968108
TI  - International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP): another
      step forward for spinal cord injury research.
AB  - For over 20 years, charitable organizations have worked to promote research that
      will cure the paralysis associated with spinal cord injury (SCI). When they began
      this quest, the consequences of SCI were thought to be permanent; that once
      damaged, the spinal cord could not be repaired. Today, the same organizations are
      credited with funding research that has realized many significant advances,
      brought new optimism and changed the outlook of researchers, clinicians and
      injured individuals alike. Progress in understanding the basic biology of spinal
      cord repair means that it is now a case of how soon useful treatments will be
      available, rather than if there will ever be anything to offer. With this in
      mind, many of the organizations that promote spinal cord research have formed an
      alliance to determine the ways in which their collaboration can hasten progress.
      The mission and objectives of this alliance, termed the International Campaign
      for Cures of Spinal Cord Injury Paralysis (ICCP), are described here.

PMID- 14968109
TI  - High-resolution analysis of genomic copy number alterations in bladder cancer by
      microarray-based comparative genomic hybridization.
AB  - We have screened 22 bladder tumour-derived cell lines and one normal urothelium
      derived cell line for genome-wide copy number changes using array comparative
      genomic hybridization (CGH). Comparison of array CGH with existing multiplex
      fluorescence in situ hybridization (M-FISH) results revealed excellent
      concordance. Regions of gain and loss were defined more accurately by array CGH,
      and several small regions of deletion were detected that were not identified by M
      FISH. Numerous genetic changes were identified, many of which were compatible
      with previous results from conventional CGH and loss of heterozygosity analyses
      on bladder tumours. The most frequent changes involved complete or partial loss
      of 4q (83%) and gain of 20q (78%). Other frequent losses were of 18q (65%), 8p
      (65%), 2q (61%), 6q (61%), 3p (56%), 13q (56%), 4p (52%), 6p (52%), 10p (52%),
      10q (52%) and 5p (43%). We have refined the localization of a region of deletion
      at 8p21.2-p21.3 to an interval of approximately 1 Mb. Five homozygous deletions
      of tumour suppressor genes were confirmed, and several potentially novel
      homozygous deletions were identified. In all, 15 high-level amplifications were
      detected, with a previously reported amplification at 6p22.3 being the most
      frequent. Real-time PCR analysis revealed a novel candidate gene with consistent
      overexpression in all cell lines with the 6p22.3 amplicon.

PMID- 14968110
TI  - Deacetylase recruitment by the C/H3 domain of the acetyltransferase p300.
AB  - The balance between acetylation and deacetylation of histone and nonhistone
      proteins controls gene expression in a variety of cellular processes, with
      transcription being activated by acetyltransferases and silenced by deacetylases.
      We report here the formation and enzymatic characterization of a complex between
      the acetyltransferase p300 and histone deacetylases. The C/H3 region of p300 was
      found to co-purify deacetylase activity from nuclear cell extracts. A prototype
      of class I histone deacetylases, HDAC1, interacts with p300 C/H3 domain in vitro
      and in vivo. The p300-binding protein E1A competes with HDAC1 for C/H3 binding;
      and, like E1A, HDAC1 overexpression interferes with either activation of Gal4p300
      fusion protein or p300-dependent co-activation of two C/H3-binding proteins, MyoD
      and p53. The exposure to deacetylase inhibitors could reverse the dominant
      negative effect of a C/H3 fragment insulated from the rest of the molecule, on
      MyoD- and p53-dependent transcription, whereas inhibition by E1A was resistant to
      trichostatin A. These data support the hypothesis that association between
      acetyltransferases and deacetylases can control the expression of genes
      implicated in cellular growth and differentiation, and suggest that the dominant
      negative effect of the p300 C/H3 fragment relies on deacetylase recruitment.

PMID- 14968111
TI  - Modulation of p53 transcription regulatory activity and post-translational
      modification by hepatitis C virus core protein.
AB  - Oncogenic virus proteins often target to tumor suppressor p53 during virus life
      cycle. In the case of hepatitis C virus (HCV) core protein, it has been shown to
      affect p53-dependent transcription. Here, we further characterized the in vitro
      and in vivo interactions between HCV core protein and p53 and showed that these
      two proteins colocalized in subnuclear granular structures and the perinuclear
      area. By use of a reporter assay, we observed that while low level of HCV core
      protein enhanced the transactivational activity of p53, high level of HCV core
      protein inhibited this activity. In both cases, however, HCV core protein
      increased the p53 DNA-binding affinity in gel retardation analyses, likely due to
      the hyperacetylation of p53 Lys(373) and Lys(382) residues. Additionally, HCV
      core protein, depending on its expression level, had differential effects on the
      Ser(15) phosphorylation of p53. Moreover, HCV core protein could rescue p53
      mediated suppressive effects on both RNA polymerase I and III transcriptions.
      Collectively, our results indicate that HCV core protein targets to p53 pathway
      via at least three means: physical interaction, modulation of p53 gene regulatory
      activity and post-translational modification. This feature of HCV core protein,
      may potentially contribute to the HCV-associated pathogenesis.

PMID- 14968112
TI  - Identification of NPM-ALK interacting proteins by tandem mass spectrometry.
AB  - Constitutive overexpression of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)
      is a key oncogenic event in anaplastic large-cell lymphomas with the
      characteristic chromosomal aberration t(2;5)(p23;q35). Proteins that interact
      with ALK tyrosine kinase play important roles in mediating downstream cellular
      signals, and are potential targets for novel therapies. Using a functional
      proteomic approach, we determined the identity of proteins that interact with the
      ALK tyrosine kinase by co-immunoprecipitation with anti-ALK antibody, followed by
      electrospray ionization and tandem mass spectrometry (MS/MS). A total of 46
      proteins were identified as unique to the ALK immunocomplex using monoclonal and
      polyclonal antibodies, while 11 proteins were identified in the NPM
      immunocomplex. Previously reported proteins in the ALK signal pathway were
      identified including PI3-K, Jak2, Jak3, Stat3, Grb2, IRS, and PLCgamma1. More
      importantly, many proteins previously not recognized to be associated with NPM
      ALK, but with potential NPM-ALK interacting protein domains, were identified.
      These include adaptor molecules (SOCS, Rho-GTPase activating protein, RAB35),
      kinases (MEK kinase 1 and 4, PKC, MLCK, cyclin G-associated kinase, EphA1, JNK
      kinase, MAP kinase 1), phosphatases (meprin, PTPK, protein phosphatase 2
      subunit), and heat shock proteins (Hsp60 precursor). Proteins identified by MS
      were confirmed by Western blotting and reciprocal immunoprecipitation. This study
      demonstrates the utility of antibody immunoprecipitation and subsequent peptide
      identification by tandem mass spectrometry for the elucidation of ALK-binding
      proteins, and its potential signal transduction pathways.

PMID- 14968113
TI  - Cdc25C phosphorylation on serine 191 by Plk3 promotes its nuclear translocation.
AB  - Mitosis in human cells is initiated at the end of G2 by activation of the
      Cdc2/cyclin B complex. Activation occurs by dephosphorylation of the inhibitory
      residues, threonine 14 (T14) and tyrosine 15 (Y15), on Cdc2 by the Cdc25C
      phosphatase. Entry into mitosis is regulated by the subcellular relocalization of
      Cdc2/cyclin B, which is rapidly imported into the nucleus at the end of G2. Here,
      we show that polo-like kinase 3 (Plk3) is able to phosphorylate Cdc25C primarily
      on S191, and to a lesser extent on S198 in vitro, both of which are within a
      nuclear exclusion motif. Following transfection, the S191D Cdc25C mutant leads to
      an enhanced accumulation of Cdc25C in the nucleus, while the S191A mutant
      facilitated the Cdc25C nuclear exclusion. Furthermore, translocation of Cdc25C to
      the nucleus was accompanied by a decrease in Cdc2 phosphorylation on Y15. Plk3-WT
      overexpression led to a sharp increase in Cdc25C nuclear accumulation, while Plk3
      KD overexpression failed to do so. The effect of Plk3 overexpression on Cdc25C
      was reversed by coexpression of a Plk3 siRNA. These results support a role for
      the polo kinases in coordinating the translocation and perhaps the timing of both
      Cdc25C and its target Cdc2/cyclin B to the nucleus upon entry into mitosis.

PMID- 14968114
TI  - A revised and complete map of the chicken c-mil/raf-1 locus.
AB  - The chicken c-mil/raf-1 gene (formerly also known as c-mht) was originally
      identified in the search for the cellular counterpart to the v-mil oncogene of
      the Mill Hill 2 retrovirus and was among the first cellular proto-oncogenes
      discovered. Although the c-mil/raf-1 promotor, as well as the exons transduced
      into v-mil, were characterized in detail, an entire map of this locus has never
      been published. Here, we now report the location of five previously unmapped
      exons. In addition, we have noticed inconsistent numbering of the c-mil/raf-1
      exons in the literature and the GenBank database. Thus, we provide here a
      complete map of the c-mil/raf-1 gene and a revision of the exon numbers.
      Comparison of the chicken c-mil/raf-1 gene with those of other vertebrates
      suggests that the numbers and lengths of the translated exons of the raf-1 locus
      were established early in the vertebrate lineage and have been conserved during
      the divergent evolution of teleosts and tetrapods.

PMID- 14968115
TI  - Expression of human papillomavirus type 16 E6 and E7 oncoproteins in primary
      foreskin keratinocytes is sufficient to alter the expression of angiogenic
      factors.
AB  - Human papillomavirus (HPV) 16 is involved in causing cervical cancer. The E6 and
      E7 proteins of HPV 16 immortalize human keratinocytes and this is due, at least
      in part, to inactivation of the tumor suppressor proteins p53 and pRB. These
      tumor suppressor proteins also regulate the expression of pro- and antiangiogenic
      factors by cells. For this reason, experiments were conducted to determine
      whether the expression of E6 and E7 in primary keratinocytes alters the phenotype
      of these cells such that they express diminished levels of antiangiogenic factors
      and/or increased levels of proangiogenic factors. To avoid variances in
      experimental observations, pools of human foreskin keratinocytes from multiple
      sources were infected with recombinant retrovirus expressing HPV 16 E6 and E7 or
      control retrovirus. Gene array analysis, RT-PCR, ELISAs and Western blotting
      showed that in cells expressing HPV 16 E6 and E7, expression levels of two potent
      angiogenesis inhibitors, thrombospondin-1 and maspin, were lower compared to
      controls. Additionally, major angiogenesis inducers, interleukin-8 and vascular
      endothelial growth factor (VEGF), were increased relative to controls. VEGF can
      be produced as multiple splice variants, all of which are required for the
      formation of patent blood vessels. The expression of HPV 16 E6 and E7 in
      keratinocytes augmented expression of VEGF 121, 145, 165 and 189. These
      observations show that HPV 16 E6 and E7 alter the phenotype of primary
      keratinocytes, diminishing expression of inhibitors and increasing expression of
      inducers of angiogenesis. This altered phenotype may permit keratinocytes
      infected by HPV 16 to play a role in the progression of cancer by permitting
      tumors to acquire a blood supply permissive of growth and spread.

PMID- 14968116
TI  - Androgens target prohibitin to regulate proliferation of prostate cancer cells.
AB  - Proteins involved in the growth response of prostate cancer cells to androgen
      were investigated by comparing the proteomes of LNCaP cells treated with vehicle
      or androgen. Whole-cell lysates were separated by two-dimensional PAGE, and HPLC
      MS/MS was used to identify androgen-regulated proteins. Prohibitin, a protein
      with cell-cycle regulatory activity, was shown to be downregulated by 50%
      following androgen stimulation. Western blot and reverse transcription-PCR
      experiments confirmed the result and showed that regulation occurs at the level
      of transcription. To determine the importance of prohibitin in androgen
      stimulated growth, we used transient transfection to overexpress the protein and
      RNA interference to knock down the protein. Subsequent FACS analysis showed that
      cells with reduced levels of prohibitin showed a slight but reproducible increase
      in the percentage of population in cell cycle, while cells with increased
      prohibitin levels showed a clear reduction in the percentage entering cell cycle,
      following dihydrotestosterone stimulation, when compared to untransfected
      controls. Confocal microscopy showed localization of prohibitin in the nucleus as
      well as the mitochondria of LNCaP cells. It therefore seems that the regulation
      of prohibitin is a vital part of the cellular growth response to androgen
      stimulation in LNCaPs and prohibitin may have a nuclear regulatory role in cell
      cycle progression.

PMID- 14968117
TI  - Modeling formalin fixation and antigen retrieval with bovine pancreatic
      ribonuclease A: I-structural and functional alterations.
AB  - Understanding the chemistry of protein modification by formaldehyde is central to
      developing improved methods to recover proteins from formalin-fixed paraffin
      embedded tissues for proteomic analysis and to improve protein immunoreactivity
      for immunohistochemical studies. We used biophysical techniques to investigate
      the effects of formaldehyde treatment on bovine pancreatic ribonuclease A (RNase
      A). Treatment of RNase A with formaldehyde was shown by gel electrophoresis to
      lead to the rapid formation of intra- and intermolecular protein cross-links.
      Thermal studies revealed that these protein cross-links significantly increased
      the thermal denaturation temperature of RNase A preparations. Analysis of
      formaldehyde-treated RNase A oligomers isolated by gel chromatography revealed
      that intramolecular protein cross-links are primarily responsible for the
      increase in protein thermostability. Formaldehyde treatment also lowered the
      isoelectric point of the enzyme from 9.45 to the 6.0-7.4 range. Optical
      spectroscopic studies demonstrated that the formaldehyde-induced modifications
      did not significantly alter the secondary or tertiary structure of RNase A.
      Heating formaldehyde-treated RNase A at 65 degrees C resulted in a significant
      reversal of the protein intra- and intermolecular cross-links and led to a
      partial restoration of enzymatic activity.

PMID- 14968118
TI  - Vascular endothelial growth factor VEGF189 induces human neutrophil chemotaxis in
      extravascular tissue via an autocrine amplification mechanism.
AB  - Vascular endothelial growth factor (VEGF) is a potent and specific endothelial
      cell mitogen involved in normal and pathological angiogenesis. Our group recently
      reported that, among the several VEGF isoforms, VEGF189 (V189) is selectively
      induced in decidual endometrial cells during the mid-late phase of the menstrual
      cycle, together with polymorphonuclear neutrophil (PMN) influx. We thus compared
      the effects of various VEGF isoforms on PMN migration in vitro, and the
      mechanisms involved. In transmigration and under-agarose assays, V189 was both
      chemotactic and chemokinetic for PMN, while VEGF165 (V165) was only chemokinetic.
      The chemokinetic effect of V189 for PMN was blocked by neutralizing anti-VEGF
      antibodies, but not by neutralizing anti-KDR antibodies, suggesting that the Flt
      1 VEGF receptor that is expressed in PMN mediates these effects. Flow cytometric
      analysis of several adhesion molecules at the PMN surface showed that all VEGF
      isoforms slightly upregulated beta1- and beta2-integrins and PECAM, and
      downregulated L-selectin; all these molecules are activation markers. The
      involvement of beta1-integrins was further supported by the ability of blocking
      antibodies to reduce VEGF-induced PMN migration. As human PMN can secrete several
      cytokines and growth factors, the selective secretion of VEGF isoforms was also
      further examined. RT-PCR analysis showed that V165 mRNA was more strongly
      expressed than V189 mRNA. Conversely, the major protein isoform secreted after
      optimal PMN degranulation was V189, which was located in both azurophilic and
      specific granules. PMN-derived VEGF can thus modulate PMN migration. This
      autocrine amplification mechanism would allow sustained VEGF release to occur at
      inflammatory sites, and may contribute to both normal and pathological
      angiogenesis.

PMID- 14968119
TI  - Immune system and prognosis in colorectal cancer: a detailed immunohistochemical
      analysis.
AB  - The efficacy of tumor cell-immune cell interactions depends on a number of
      factors, for example, the expression of HLA-I on tumor cells, the type of immune
      cell, the accessibility of tumor cells for immune cells and the expression of
      immunogenic epitopes. We assessed infiltration of CD4+, CD8+, CD56+ and CD57+
      cells in the tumor epithelium, tumor stroma and advancing tumor margin of 93
      colorectal carcinomas and correlated this to clinicopathological parameters, the
      expression of HLA-A and HLA-B/C on tumor cells, the presence of a basal membrane
      (BM)-like structure surrounding tumor nodules and the presence of microsatellite
      instability/mutator phenotype (absent MLH-1 expression). The median
      intraepithelial CD4+, CD8+, CD56+ and CD57+ cell infiltrations were 3, 23, 0 and
      0 cells/mm(2) tumor, respectively. HLA-A/BC expression by tumor cells was normal
      in 28/43%, heterogeneous in 59/48% and absent in 13/9% of the cases. A BM-like
      structure surrounding the tumor nodules was absent, present and thick in 47, 38
      and 15% of the cases. Six cases lost MLH1 expression. There was a positive
      correlation between leukocyte infiltration in the three compartments for CD4+,
      CD8+, CD56+ (partly) and CD57+ (all P<0.05) cell infiltration. Intraepithelial
      CD8+ cell infiltration inversely correlated with HLA-A (P=0.04) and HLA-B/C
      expression (P=0.04). Intraepithelial CD57+ cell infiltration inversely correlated
      with HLA-B/C expression (P=0.04). Moreover, intraepithelial infiltration of CD8+
      and CD57+ cells was inversely correlated to the presence of a BM-like structure
      (P=0.003 and 0.04, respectively). Uni- and multivariate analyses showed that a
      lower tumor stage (P=0.004) and marked infiltration of CD8+ (P=0.04) and CD57+
      cells (P=0.05) at the advancing tumor margin were independent prognostic factors
      for a longer disease-free survival. Loss of MLH1 expression was correlated with a
      significantly higher intraepithelial CD8+ and CD57+ cell infiltration. We
      conclude that infiltration of CD8+ and CD57+ cells are important prognostic
      factors in colorectal cancer. However, their interaction with tumor cells is
      inversely correlated to the presence of HLA-I on tumor cells and a thick BM-like
      structure around tumor islets. Our data indicate that NK cells might play an
      important role in the immune surveillance in colorectal cancer patients.

PMID- 14968120
TI  - Immunogenetic analysis of gastric MALT lymphoma-like lesions induced by
      Helicobacter pylori infection in neonatally thymectomized mice.
AB  - Most gastric mucosa-associated lymphoid tissue (MALT) lymphomas are caused by
      Helicobacter pylori (H. pylori) infection. We previously reported that acquired
      lymphoid follicles with germinal centers were induced by H. pylori infection in
      neonatally thymectomized (nTx) mice. In the present study, we developed gastric
      MALT lymphoma-like lesions in nTx mice by long-term H. pylori infection, and
      performed immunogenetic analyses. BALB/c mice were thymectomized on the 3rd day
      after birth. At 6 weeks of age, mice were orally infected with 10(8) H. pylori
      and serially killed 2, 4, 6, and 12 months later. Normal BALB/c and noninfected
      nTx mice served as controls. Follicle formation occurred after 2 months of H.
      pylori infection in the nTx mice. Follicle formation and infiltration of
      intraepithelial lymphocytes progressed in a time-dependent manner.
      Lymphoepithelial lesions, a characteristic feature of MALT lymphoma, also
      occurred in a time-dependent manner (100% at 12 months). Serum
      immunoelectrophoresis revealed a monoclonal band (M-protein) in 30% (3/10) of
      mice 6 months after infection. M-protein-positive mice had amplification of one
      or two IgM and/or IgG heavy-chain genes in the gastric B lymphocytes, as
      determined with polymerase chain reaction, suggesting mono- or oligoclonality.
      Overexpression of Bcl-X(L) protein was immunohistologically observed in the
      infiltrating B lymphocytes and in some follicular B lymphocytes in 80% (8/10) of
      the cases at 12 months. Thus, H. pylori infection is involved in the development
      of gastric MALT lymphoma-like lesions in nTx mice. Our mouse model is useful for
      clarifying the pathogenetic mechanism of gastric MALT lymphoma by H. pylori
      infection.

PMID- 14968121
TI  - Overexpression of autocrine motility factor in metastatic tumor cells: possible
      association with augmented expression of KIF3A and GDI-beta.
AB  - Autocrine motility factor (AMF), which is identical to phosphohexose isomerase
      (PHI)/glucose-6-phosphate isomerase (GPI), a ubiquitous enzyme essential for
      glycolysis, neuroleukin (NLK), a neurotrophic growth factor, and maturation
      factor (MF) mediating the differentiation of human myeloid cells, enhances the
      motility and metastatic ability of tumor cells. AMF/PHI activity is elevated in
      the serum or urine in patients with malignant tumors. Here, we constructed an
      amf/phi/nlk/mf gene using adenovirus vector and transfected into two tumor cell
      lines. Overexpression of AMF/PHI/NLK/MF enhanced AMF secretion into the culture
      media in both tumor cell lines. However, upregulation of motility and metastatic
      ability was found only in metastatic fibrosarcoma cells expressing an AMF
      receptor, gp78, and was not found in gp78-undetectable osteosarcoma cells. Thus,
      not only serum AMF activity but also gp78-expression in tumor cells may be
      required for metastasis-related motility induction. With the use of microarray
      analyses, we detected two augmented genes, rho GDP dissociation inhibitor beta
      and kinesin motor 3A, as well as AMF itself. The RNA message and protein
      expression of these two molecules was confirmed to be upregulated, suggesting a
      possible association with AMF-induced signaling for cell motility and metastasis.

PMID- 14968122
TI  - Native state stabilization by NSAIDs inhibits transthyretin amyloidogenesis from
      the most common familial disease variants.
AB  - Transthyretin (TTR) tetramer dissociation and misfolding affords a monomeric
      amyloidogenic intermediate that misassembles into aggregates including amyloid
      fibrils. Amyloidogenesis of wild-type (WT) TTR causes senile systemic amyloidosis
      (SSA), whereas fibril formation from one of the more than 80 TTR variants leads
      to familial amyloidosis, typically with earlier onset than SSA. Several
      nonsteroidal anti-inflammatory drugs (NSAIDs) stabilize the native tetramer,
      strongly inhibiting TTR amyloid fibril formation in vitro. Structure-based
      designed NSAID analogs are even more potent amyloid inhibitors. The effectiveness
      of several NSAIDs, including diclofenac, diflunisal, and flufenamic acid, as well
      as the diclofenac analog, 2-[(3,5-dichlorophenyl) amino] benzoic acid (inhibitor
      1), has been demonstrated against WT TTR amyloidogenesis. Herein, the efficacy of
      these compounds at preventing acid-induced fibril formation and urea-induced
      tetramer dissociation of the most common disease-associated TTR variants (V30M,
      V122I, T60A, L58H, and I84S) was evaluated. Homotetramers of these variants were
      employed for the studies within, realizing that the tetramers in compound
      heterozygote patients are normally composed of a mixture of WT and variant
      subunits. The most common familial TTR variants were stabilized substantially by
      flufenamic acid and inhibitor 1, and to a lesser extent by diflunisal, against
      acid-mediated fibril formation and chaotrope denaturation, suggesting that this
      chemotherapeutic option is viable for patients with familial transthyretin
      amyloidosis.

PMID- 14968123
TI  - Methylation of RUNX3 in various types of human cancers and premalignant stages of
      gastric carcinoma.
AB  - Accumulating evidence has identified a mechanism potentially responsible for the
      inactivation of tumor suppressor genes, namely transcriptional silencing by
      aberrant methylation of CpG islands. A previous study has shown the loss of RUNX3
      expression, due to aberrant methylation of its CpG island, in gastric cancer cell
      lines, suggesting that RUNX3 is a target for epigenetic gene silencing in gastric
      carcinogenesis. However, there are limited data on the methylation status of
      RUNX3 in the neoplastic and non-neoplastic tissues in various types of human
      cancers, including gastric cancer. Here, we report that 60% of gastric cancer
      cell lines and 64% of primary gastric carcinomas (n=75) were methylated at the
      RUNX3 CpG island. RUNX3 methylation was also detected in hepatocellular
      carcinomas (73%, n=48), larynx cancers (62%, n=37), lung cancers (46%, n=24),
      breast cancers (25%, n=25), prostate cancers (23%, n=44), endometrial cancers
      (12.5%, n=24), colon cancers (4.9%, n=61) and uterine cervical cancers (2.5%,
      n=40), showing that RUNX3 methylation is not restricted to gastric cancer.
      Interestingly, the RUNX3 methylation was especially frequent in tumors from
      tissues of a foregut derivative, that is, the stomach, liver, larynx and lung.
      Next, the methylation status of RUNX3 in various non-neoplastic tissues was
      examined, including the premalignant lesions of gastric carcinomas. The RUNX3
      methylation was found in 8.1% of chronic gastritis (n=99), 28.1% of intestinal
      metaplasia (n=32), 27.3% of gastric adenomas (n=77) and 64% of gastric carcinomas
      (n=75), but not in chronic hepatitis B, normal prostate and colon mucosa, even
      though in cases of chronic hepatitis, the methylation frequency of its neoplastic
      tissues was very high. In conclusion, RUNX3 methylation is frequently found in
      human cancers, including gastric cancer, and is mostly cancer specific, with the
      exception of the stomach, and thus, might be useful as a potential diagnostic
      biomarker of cancer.

PMID- 14968124
TI  - Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases mRNA
      transcripts in the bronchial secretions of asthmatics.
AB  - Asthma is a chronic inflammatory disease characterized by profound extracellular
      matrix changes referred to as bronchial remodelling. In this study, we evaluated
      matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) mRNA
      expression in bronchial secretions of asthmatics and correlated MMPs modulations
      with the lung function as a reflection of the bronchial extracellular matrix
      remodelling. Quantitative RT-PCR was performed on cell pellets obtained from
      induced sputum in order to detect the mRNAs for MMP-1, -2, -3, -8, -9, -12, -13
      TIMP-1, -2, while semiquantitative RT-PCR was performed to assess the expression
      of MMP-7, monocyte chemoattractant protein-1 (MCP-1) and transforming growth
      factor-beta(1) (TGF-beta(1)). The mRNA transcripts for MMP-1, TIMP-1 and monocyte
      chemoattractant protein-1 (MCP-1) were increased in cell pellets of induced
      sputum from asthmatics when compared to controls (P<0.05), and the intensity of
      MMP-1 mRNA expression inversely correlated with the FEV(1) in asthmatics (r=
      0.49, P<0.05). The MMP-1 mRNA/TIMP-1 mRNA ratio correlated with the levels of MCP
      1 mRNA in asthmatics (r=0.47, P<0.05). There were no differences between the
      groups with respect to mRNA coding for MMP-2, -3, -7, -8, -9, -12, -13, -14, TIMP
      2 and TGF-beta(1). We conclude that cells contained in the bronchial secretions
      from asthmatics express higher amounts of mRNA for MMP-1 and TIMP-1, perhaps
      related to an increased expression of MCP-1, which might contribute to the
      extracellular matrix changes observed during airway remodelling.

PMID- 14968125
TI  - Recurrent perivascular inflammation induced by lipopolysaccharide (endotoxin)
      results in the formation of atheromatous lesions in vivo.
AB  - Bacteria and viruses are suspected to induce arteriosclerosis; however, most
      investigators have focused on coincidences rather than causal relationships. The
      aim of this work was to establish a rabbit model in which the vessel reaction to
      local perivascular injection of defined bacterial products can be analyzed. A
      total of 23 rabbits were randomized to four groups. Groups A and B were fed a
      normal diet, groups C and D were fed a cholesterol-enriched diet. Groups A and C
      were treated with a single perivascular injection of bacterial lipopolysaccharide
      (LPS, endotoxin) placed next to auricular, carotid and femoral arteries, and
      sodium chloride placed next to the contralateral arteries (control). Group B and
      D animals were treated with repeated perivascular injections over 90 days.
      Vascular tissues (n=116 treated segments of 23 rabbits) were analyzed using
      morphometry at histology, and using immunohistochemistry to detect macrophages,
      lymphocytes and vascular smooth muscle cells. LPS treatment resulted in transient
      focal intima thickening. After single LPS application, no increase in
      atheromatous lesion formation was observed in comparison with controls (group C,
      lesion area index 0.031+/-0.012 vs 0.015+/-0.006, P=1.0). Repeated LPS
      application resulted in significant atheromatous lesion formation compared with
      saline control (group D, lesion area index 0.148+/-0.049 vs 0.008+/-0.006,
      P=0.003) in hypercholesterolemic rabbits. Repeated LPS inflammation in
      normocholesterolemic did not lead to atheromatous lesion formation (intima media
      ratio 0.04+/-0.01 vs 0.04+/-0.007, P=1.0). Single perivascular administration of
      low-dose bacterial LPS resulted in transient focal intimal thickening, while
      significant increase in lesion formation occurred after repeated LPS application
      in cholesterol-fed animals. In conclusion, this animal model will allow the
      assessment of the impact of defined dosages of different bacterial pathogens onto
      the vascular wall in the context of atherogenesis. The atheromatous lesion
      promoting effect of repeated perivascular administration of LPS supports the
      hypothesis that bacterial pathogens may be involved in atherogenesis.

PMID- 14968126
TI  - Deletions of chromosome 8p and loss of sFRP1 expression are progression markers
      of papillary bladder cancer.
AB  - Many molecular alterations are known to occur in urothelial carcinoma of the
      bladder, but their significance for tumor progression is poorly understood.
      Deletions of chromosome 8p are frequently found in several tumor types and are
      often associated with progressive disease. In all, 99 bladder tumors were
      screened for deletions at 8p using loss of heterozygosity (LOH) and multicolor
      fluorescence in situ hybridization FISH analyses. Allelic loss on chromosome 8p
      in at least one marker was found in 25/99 (25%) tumors. There was a significant
      correlation of 8p deletions with invasive tumor growth and a highly significant
      association with papillary growth pattern in patients with invasive disease. cDNA
      array analyses revealed that secreted Frizzled-related protein 1 (sFRP1), an
      antagonist of Frizzled receptors and Wnt pathway activation on chromosome 8p12
      11.1, is frequently downregulated in bladder cancer. To investigate sFRP1 as a
      candidate for a putative progression-related gene on 8p, urothelial cell lines
      and primary urothelial carcinomas were screened for sFRP1 expression using
      quantitative real-time PCR, Northern blot, immunofluorescence and
      immunohistochemistry (IHC). Of the investigated bladder cancers, 38% showed loss
      of sFRP1 expression by quantitative RT-PCR. Evaluation of the protein expression
      by IHC using tissue microarrays containing 776 bladder cancers revealed loss or
      strong reduction of sFRP1 expression in 66% of cases. SFRP1 loss was associated
      with higher tumor stage and grade and shorter overall survival. In addition, loss
      of sFRP1 was an independent indicator of poor survival in patients with papillary
      but not with muscle invasive bladder cancer. There were neither mutations in the
      coding region of sFRP1 nor homozygous deletions at 8p12-11.21. However, promoter
      methylation was detected using methylation-specific PCR in 29% of cases. In
      conclusion, we could show a close correlation of chromosome 8p deletions and
      progression of papillary bladder tumors. The sFRP1 gene on chromosome 8p12-11.1
      could be a candidate gene for the predicted, progression-related tumor suppressor
      gene in bladder cancer and could contribute to urothelial carcinogenesis.

PMID- 14968127
TI  - Negative mood-induced overeating in obese binge eaters: an experimental study.
AB  - OBJECTIVES: To test the hypotheses that induction of negative mood in obese binge
      eaters would increase food intake, and that this would be greatest in those who
      were highly restrained. DESIGN: Experimental manipulation of mood (neutral vs sad
      film) prior to the presentation of food in a taste test. PARTICIPANTS: A total of
      40 obese female binge eaters (41.7 y, mean BMI=40.2 kg/m(2)). MEASURES: Visual
      analogue assessment of mood and hunger motivation, dietary restraint (Dutch
      Eating Behaviour Questionnaire), and food intake. RESULTS: Exposure to the sad
      film resulted in a significant decrease in mood for both restrained and
      unrestrained participants. Those in the negative mood condition ate significantly
      more food, and the restrained eaters consumed the most. However, the expected
      restraint by mood interaction just failed to reach significance (P=0.06)
      CONCLUSIONS: The salience of negative mood in promoting overeating was confirmed.
      Conversely, dietary restraint had no significant impact on food intake. Further
      experimental work on binge eating in this group would be of value in clarifying
      the role of dieting and informing treatment approaches.

PMID- 14968128
TI  - A prospective study of body size and colon cancer mortality in Japan: The JACC
      Study.
AB  - OBJECTIVE: To determine whether body size measurements are risk factors for colon
      cancer death among the Japanese. DESIGN AND SUBJECTS: A nationwide prospective
      study, the Japan Collaborative Cohort (JACC) Study from 1988 to 1999. The present
      analysis included 43 171 men and 58 775 women aged 40-79 y who respond to a
      questionnaire on current weight and height, weight around 20 y of age, and other
      lifestyle factors. Body mass index (BMI) at baseline and 20 y of age (B-BMI and
      20-BMI, respectively) were calculated. RESULTS: We identified 127 deaths from
      colon cancer during the follow-up of 424 698 person-years among men and 122
      deaths during the follow-up of 591 787 person-years among women. After
      adjustments for the lifestyle factors known to modify the risk of colon cancer,
      weight at baseline showed a significant positive association in women, while no
      such association was seen in men. There was also a significant trend of
      increasing risk with the increase in B-BMI among women. Women with B-BMI >/=28
      kg/m(2) had a relative risk (RR) of 3.41 (95% confidence interval (CI): 1.44
      8.06) compared with those with BMI of 20-<22 kg/m(2). 20-BMI also presented the
      same trend of increasing risk as B-BMI. Women with 20-BMI of <22 and B-BMI of >26
      kg/m(2), that is, excessive BMI gain, had a high RR of 3.41 (95% CI 1.29-9.02)
      compared with those with 20-BMI of <22 and B-BMI of <22 kg/m(2). There were no
      corresponding trends of colon cancer risk for B-BMI, 20-BMI, or BMI change among
      men. CONCLUSIONS: These study data suggest that obesity and excessive weight gain
      are associated with the risk of colon cancer death in Japanese women but no such
      relationship was found in Japanese men.

PMID- 14968129
TI  - Massive obesity in adolescents: dietary interventions and behaviours associated
      with weight regain at 2 y follow-up.
AB  - OBJECTIVE: To compare the influence of weight-reducing diets containing different
      amounts of protein and CHO on body composition in obese adolescents and to
      examine dietary and physical activity behaviours during follow-up. METHODOLOGY: 
      DESIGN: Prospective randomised study comparing two weight-reducing diets with the
      same energy (1750 kcal) and fat (31%) content, but different protein and
      carbohydrate contents: PROT- (15% protein, 54% CHO) vs PROT+ (19% protein, 50%
      CHO). PATIENTS: Massively obese 11- to 16-year-old children (32 boys and 89
      girls). SETTING: A 9-month treatment in a medical centre (boarding school) plus a
      2-y follow-up in free-living patients examined at home 1 and 2 y after treatment.
      MEASUREMENTS: Anthropometry, bioelectrical impedance, nutritional intakes and
      physical activity. RESULTS: Of the 121 eligible children (61 in PROT- and 60 in
      PROT+), 82% completed the trial until the end of weight loss treatment and 60%
      were followed 2 y after treatment. Body mass index (BMI) value at inclusion was
      36.3 kg/m(2) or 4.3 z-scores (2.9-5.9). BMI z-score decreased to 1.7 at the end
      of treatment and went back to 2.8 (0.8-6.1) 2 y after treatment. This
      corresponded to a weight loss of 30.3 kg and weight regain of 21.3 kg. After
      treatment, energy intake increased and physical activity decreased. The
      contribution of energy ingested at breakfast decreased while snacking increased.
      For all measurements, no dietary group differences existed at baseline or at any
      time during the intervention and follow-up. CONCLUSION: A higher protein content
      of the diet did not confer any benefit in the treatment of childhood obesity.
      Substantial weight loss was obtained with a moderately energy-restricted diet and
      normal fat content. After weight loss, mean weight increased in spite of moderate
      energy intake, together with a drift towards obesity-associated behavioural
      patterns. The causes of the inability to adopt normal weight subjects' behaviour
      permanently deserve to be investigated further.

PMID- 14968130
TI  - eIF4E isoform 2 in Schizosaccharomyces pombe is a novel stress-response factor.
AB  - Cap-binding proteins of the elF4E family are generally involved in mediating
      ribosome recruitment to capped mRNA via an interaction with the initiation factor
      elF4G. However, Schizosaccharomyces pombe has two elF4E isoforms, one of which
      (elF4E2, encoded by tif452) has a relatively low affinity for elF4G. We show that
      tif452 is required for specific stress responses. An S. pombe, tif452delta mutant
      manifests slow growth under conditions of nutrient, temperature and salt stress.
      elF4E2 shows a distinct subcellular distribution to elF4E1, the cap-binding
      factor that is required for mainstream translation. In response to salt stress,
      the cellular level of elF4E2 increases, whereas the amount of intact elF4G
      decreases, leaving elF4E2 as the predominant elF4E isoform in a cell deficient in
      ElF4G. The presence of elF4E2 modifies the competence of S. pombe ribosomes to
      translate mRNAs with structured leaders in vivo. The tif452 promoter has putative
      stress-response (T-rich) motifs, whereas elF4E2 seems to be a new type of stress
      response factor.

PMID- 14968131
TI  - The yeast coexpression network has a small-world, scale-free architecture and can
      be explained by a simple model.
AB  - We investigated the gene coexpression network in Saccharomyces cerevisiae, in
      which genes are linked when they are coregulated. This network is shown to have a
      scale-free, small-world architecture. Such architecture is typical of biological
      networks in which the nodes are connected when they are involved in the same
      biological process. Current models for the evolution of intracellular networks do
      not adequately reproduce the features that we observe in the network. We
      therefore derive a new model for its evolution based on the observation that
      there is a positive correlation between the sequence similarity of paralogues and
      their probability of coexpression or sharing of transcription factor binding
      sites (TFBSs). The simple, neutralist's model consists of (1) coduplication of
      genes with their TFBSs, (2) deletion and duplication of individual TFBSs and (3)
      gene loss. A network is constructed by connecting genes that share multiple
      TFBSs. Our model reproduces the scale-free, small-world architecture of the
      coregulation network and the homology relations between coregulated genes without
      the need for selection either at the level of the network structure or at the
      level of gene regulation.

PMID- 14968132
TI  - Molecular insights into the interaction of PYM with the Mago-Y14 core of the exon
      junction complex.
AB  - The exon junction complex (EJC) is deposited on mRNAs as a consequence of
      splicing and influences postsplicing mRNA metabolism. The Mago-Y14 heterodimer is
      a core component of the EJC. Recently, the protein PYM has been identified as an
      interacting partner of Mago-Y14. Here we show that PYM is a cytoplasmic RNA
      binding protein that is excluded from the nucleus by Crm1. PYM interacts directly
      with Mago-Y14 by means of its N-terminal domain. The crystal structure of the
      Drosophila ternary complex at 1.9 A resolution reveals that PYM binds Mago and
      Y14 simultaneously, capping their heterodimerization interface at conserved
      surface residues. Formation of this ternary complex is also observed with the
      human proteins. Mago residues involved in the interaction with PYM have been
      implicated in nonsense-mediated mRNA decay (NMD). Consistently, human PYM is
      active in NMD tethering assays. Together, these data suggest a role for PYM in
      NMD.

PMID- 14968134
TI  - Temporal dissection of Bax-induced events leading to fission of the single
      mitochondrion in Trypanosoma brucei.
AB  - The protozoan Trypanosoma brucei has a single mitochondrion and lacks an
      apoptotic machinery. Here we show that expression of the proapoptotic protein Bax
      in T. brucei causes the release of cytochrome c, the depolarization of the
      mitochondrial membrane potential and mitochondrial fission. However, in contrast
      to mammalian cells, the three events are temporally well separated. The release
      of cytochrome c from the intermembrane space precedes mitochondrial fission,
      showing that it does not depend on mitochondrial fragmentation. Furthermore,
      halting Bax expression allows some cells to recover even after mitochondrial
      fission, the last recorded event, went to completion, indicating that all three
      Bax-induced events are, in principle, reversible.

PMID- 14968135
TI  - Convergent evolution of gene networks by single-gene duplications in higher
      eukaryotes.
AB  - By combining phylogenetic, proteomic and structural information, we have
      elucidated the evolutionary driving forces for the gene-regulatory interaction
      networks of basic helix-loop-helix transcription factors. We infer that recurrent
      events of single-gene duplication and domain rearrangement repeatedly gave rise
      to distinct networks with almost identical hub-based topologies, and multiple
      activators and repressors. We thus provide the first empirical evidence for scale
      free protein networks emerging through single-gene duplications, the dominant
      importance of molecular modularity in the bottom-up construction of complex
      biological entities, and the convergent evolution of networks.

PMID- 14968136
TI  - Implications of early airflow decline after myeloablative allogeneic stem cell
      transplantation.
AB  - The clinical significance of early airflow decline after myeloablative allogeneic
      hematopoietic SCT is uncertain. We performed a retrospective cohort analysis to
      determine if airflow decline by day 100 is associated with later development of
      transplant-related airflow obstruction (AFO) and increased mortality risk.
      Overall, 750 (40%) patients had airflow decline by day 100. Development of
      airflow decline by day 100 was associated with an increased risk for AFO at 1
      year (relative risk 2.6, 95% confidence interval 2.1-3.1) but not with an
      increase in mortality risk (hazard ratio (HR) 0.86, P=0.05). However, patients
      with the fastest rate of decline between day 100 and 1 year (12.5% per year +/
      24) had the highest mortality risk (HR 3.2, P<0.001). In conclusion, airflow
      measurements made on day 100 do not predict the rate of airflow decline between
      day 100 and 1 year, and therefore are not useful as a single measurement for
      determining mortality risk associated with development of AFO. Closer monitoring
      of the rate of airflow decline during the first year may facilitate the timely
      detection and treatment of early airflow decline and prevent the development of
      fixed AFO and increased mortality risk after hematopoietic stem cell transplant.

PMID- 14968137
TI  - Allogeneic stem cell transplantation for patients with congenital amegakaryocytic
      thrombocytopenia (CAT).
AB  - Five patients with confirmed congenital amegakaryocytic thrombocytopenia (CAT)
      underwent stem cell transplantation (SCT) from HLA-matched related donors at King
      Faisal Specialist Hospital and Research Center (KFSHRC). The median age at SCT
      was 3.2 years (range, 0.4-5 years). Conditioning regimen consisted of busulfan
      (BU) 4 mg/kg p.o. for 4 days (total dose of 16 mg/kg), and cyclophosphamide (CY)
      50 mg/kg once daily i.v. for 4 days (total dose of 200 mg/kg). Antithymocyte
      globulin (ATG) was given i.v. at a dose of 30 mg/kg for 4 days pre-SCT (total of
      120 mg/kg); graft-versus-host disease (GVHD) prophylaxis was with cyclosporine
      and methotrexate. Four patients engrafted and are alive and transfusion
      independent with a median follow up time of 30 months (range, 16-45 months). One
      patient failed to engraft and underwent a second SCT 4 months later but died of
      respiratory failure. We conclude that the use of allogeneic SCT may be curative
      for such patients.

PMID- 14968138
TI  - Will regulation be the death of cell therapy in the United States?
AB  - Advanced cell-based therapies are rapidly evolving and there is apparent
      increasing tension between regulation and introduction of new scientific
      advances. The model and concept of product development has introduced new
      challenges for laboratories developing cell-based therapies. The scale-up of
      experimental processes to production processes is an expensive but poorly
      compensated activity. The regulatory issues including personnel and facility
      requirements for manufacturing creates significant economic barriers to academic
      centers entering the field. As yet the model of product development envisioned by
      regulatory agencies is a patented commercial product to be manufactured by a
      company or its licensed manufacturers. The alternative model of advanced blood
      banks producing products may provide wider dissemination of products to patients.
      Although regulations have sometimes been perceived to be delaying advances, the
      regulatory agencies are evolving into a cooperative, supportive position that
      will ultimately speed the introduction of safe and effective cell-based therapies
      to broad clinical use. The vision for cell-based therapies needs scientific
      breadth and regulatory understanding to benefit the greatest number of patients.

PMID- 14968140
TI  - On governance.

PMID- 14968141
TI  - The 2004 Canadian Hypertension Education Program recommendations for the
      management of hypertension: Part I--Blood pressure measurement, diagnosis and
      assessment of risk.
AB  - OBJECTIVE: To provide updated, evidence-based recommendations for the assessment
      of the diagnosis, cardiovascular risk and identifiable causes for adults with
      high blood pressure. OPTIONS: For persons in whom a high blood pressure value is
      recorded, the assignment of a diagnosis of hypertension is dependent on the
      appropriate measurement of blood pressure, the level of the blood pressure
      elevation and the duration of follow-up. In addition, the presence of concomitant
      vascular risk factors, target organ damage and established atherosclerotic
      diseases should be assessed to determine the urgency, intensity and type of
      treatment. For persons diagnosed as having hypertension, defining overall risk of
      adverse cardiovascular outcomes requires an assessment of concomitant vascular
      risk factors, including laboratory testing, a search for target organ damage and
      an assessment for modifiable causes of hypertension. Home and ambulatory blood
      pressure assessment and echocardiography are options for selected patients.
      OUTCOMES: The identification of persons at increased risk of adverse
      cardiovascular outcomes; the quantification of overall cardiovascular risk; and
      the identification of persons with potentially modifiable causes of hypertension.
      EVIDENCE: Medline searches were conducted from November 2001, one year before the
      period of the last revision of the Canadian recommendations for the management of
      hypertension, to October 2003. Reference lists were scanned, experts were polled,
      and the personal files of subgroup members and authors were used to identify
      other studies. Identified articles were reviewed and appraised using prespecified
      levels of evidence by content experts and methodological experts. VALUES: A high
      value was placed on the identification of persons at increased risk of
      cardiovascular morbidity and mortality, and persons with identifiable and
      potentially modifiable causes of hypertension. BENEFITS, HARMS AND COSTS: The
      identification of persons at higher risk of cardiovascular disease will permit
      counselling for lifestyle maneuvers and introduction of antihypertensive drugs to
      reduce blood pressure for patients with sustained hypertension. The
      identification of specific causes of hypertension may permit the use of cause
      specific interventions. For certain subgroups of patients and specific classes of
      drugs, blood pressure lowering has been associated with reduced cardiovascular
      morbidity and/or mortality. RECOMMENDATIONS: The document contains
      recommendations for blood pressure measurement, diagnosis of hypertension and
      assessment of cardiovascular risk for adults with high blood pressure. These
      include the accurate measurement of blood pressure, criteria for diagnosis of
      hypertension, and recommendations for follow-up, assessment of overall
      cardiovascular risk, routine and optional laboratory testing, assessment for
      renovascular and endocrine causes, home and ambulatory blood pressure monitoring,
      and the role of echocardiography for those with hypertension. VALIDATION: All
      recommendations were graded according to strength of evidence and voted on by the
      Canadian Hypertension Education Program Evidence-Based Recommendations Task
      Force. Only the recommendations that achieved high levels of consensus are
      reported. These guidelines will be updated annually.

PMID- 14968142
TI  - The 2004 Canadian recommendations for the management of hypertension: Part II-
      Therapy.
AB  - OBJECTIVE: To provide updated, evidence-based recommendations for the management
      of hypertension in adults. OPTIONS AND OUTCOMES: For patients who require
      pharmacological therapy for hypertension, a number of antihypertensive agents may
      be used. Randomized trials evaluating first-line therapy with diuretics, beta
      blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium channel
      blockers (CCBs), alpha-blockers, centrally acting agents or angiotensin receptor
      antagonists were reviewed. Also, randomized trials evaluating other agents, such
      as statins or acetylsalicylic acid, in patients with hypertension were reviewed.
      Changes in cardiovascular morbidity and mortality were the primary outcomes of
      interest. In addition, other relevant outcomes such as development of end-stage
      renal disease or changes in blood pressure were examined where appropriate.
      EVIDENCE: MEDLINE searches were conducted from November 2001 to October 2003 to
      update the 2001 Recommendations for the management of hypertension. Reference
      lists were scanned, experts were contacted, and the personal files of the
      subgroup members and authors were used to identify additional published studies.
      All relevant articles were reviewed and appraised independently, using
      prespecified levels of evidence by content and methodology experts.
      RECOMMENDATIONS: This document contains detailed recommendations and supporting
      evidence on treatment thresholds, target blood pressures and choice of agents for
      hypertensive patients with or without comorbidities. Lifestyle modifications are
      a key component of any antiatherosclerotic management strategy and detailed
      recommendations are contained in a separate document. Key recommendations for
      pharmacotherapy include the following: treatment thresholds and targets should
      take into account each individual's global atherosclerotic risk, target organ
      damage and comorbidities, with particular attention to systolic blood pressure;
      blood pressure should be lowered to 140/90 mmHg or less in all patients, and
      130/80 mmHg or less in those with diabetes mellitus or renal disease (125/75 mmHg
      or less in those with nondiabetic renal disease and more than 1 g of proteinuria
      per day); most adults with hypertension require more than one agent to achieve
      target blood pressures; for adults without compelling indications for other
      agents, initial therapy should include thiazide diuretics; other agents
      appropriate for first-line therapy for diastolic hypertension with or without
      systolic hypertension include beta-blockers (in those younger than 60 years), ACE
      inhibitors (in non-Blacks), long-acting dihydropyridine CCBs or angiotensin
      receptor antagonists; other agents appropriate for first-line therapy for
      isolated systolic hypertension include long-acting dihydropyridine CCBs or
      angiotensin receptor antagonists; certain comorbidities provide compelling
      indications for first-line use of other agents: in patients with angina, recent
      myocardial infarction or heart failure, beta-blockers and ACE inhibitors are
      recommended as first-line therapy; in patients with diabetes mellitus, ACE
      inhibitors or angiotensin receptor antagonists (or thiazides in patients with
      diabetes mellitus without albuminuria) are appropriate first-line therapies; and
      in patients with mild to moderate nondiabetic renal disease, ACE inhibitors are
      recommended; all hypertensive patients should have their fasting lipids screened
      and those with dyslipidemia should be treated using the thresholds, targets and
      agents as per the Recommendations for the management of dyslipidemia and the
      prevention of cardiovascular disease; and selected patients with hypertension
      should also receive statin and/or acetylsalicylic acid therapy. VALIDATION: All
      recommendations were graded according to the strength of the evidence and voted
      on by the Canadian Hypertension Education Program Evidence-Based Recommendations
      Task Force. Individuals with irreconcilable competing interests (declared by all
      members, compiled and circulated before the meeting) relative to any specific
      recommendation were excluded from voting on that recommendation. Only
      recommendations achieving at least 70% consensus are reported here. These
      guidelines will continue to be updated annually.

PMID- 14968143
TI  - The 2004 Canadian recommendations for the management of hypertension: Part III-
      Lifestyle modifications to prevent and control hypertension.
AB  - OBJECTIVE: To provide updated, evidence-based recommendations regarding the role
      of lifestyle modification in the treatment and prevention of hypertension.
      OUTCOMES: Lifestyle modification interventions including exercise, weight
      reduction, alcohol consumption, dietary modification, intake of dietary cations
      and stress management are reviewed. Antioxidants and fish oil supplements are
      also reviewed, although specific recommendations cannot be made at present.
      EVIDENCE: MEDLINE searches were conducted from January 2002 to September 2003 to
      update the 2001 recommendations for the management of hypertension. Supplemental
      searches in the Cochrane Collaboration databases were also performed. Reference
      lists were scanned, experts were contacted, and the personal files of the
      subgroup members and authors were used to identify additional published studies.
      All relevant articles were reviewed and appraised independently using
      prespecified levels of evidence by content and methodology experts.
      RECOMMENDATIONS: Key recommendations include the following: lifestyle
      modification should be extended to nonhypertensive individuals who are at risk
      for developing high blood pressure; 30 min to 45 min of aerobic exercise should
      be performed on most days (four to five days) of the week; an ideal body weight
      (body mass index 18.5 kg/m2 to 24.9 kg/m2) should be maintained and weight loss
      strategies should use a multidisciplinary approach; alcohol consumption should be
      limited to two drinks or fewer per day, and weekly intake should not exceed 14
      standard drinks for men and nine standard drinks for women; a reduced fat, low
      cholesterol diet that emphasizes fruits, vegetables and low fat dairy products,
      and maintains an adequate intake of potassium, magnesium and calcium, should be
      followed; salt intake should be restricted to 65 mmol/day to 100 mmol/day in
      hypertensive individuals and less than 100 mmol/day in normotensive individuals
      at high risk for developing hypertension; and stress management should be
      considered as an intervention in selected individuals. VALIDATION: All
      recommendations were graded according to the strength of the evidence and voted
      on by the Canadian Hypertension Education Program Evidence-Based Recommendations
      Task Force. Individuals with irreconcilable competing interests (declared by all
      members, compiled and circulated before the meeting) relative to any specific
      recommendation were excluded from voting on that recommendation. Only those
      recommendations achieving at least 70% consensus are reported here. These
      guidelines will continue to be updated annually.

PMID- 14968145
TI  - Economic evaluation of the use of irbesartan and amlodipine in the treatment of
      diabetic nephropathy in patients with hypertension in Canada.
AB  - BACKGROUND: Irbesartan has been shown to reduce the doubling of serum creatinine
      (a strong predictor of progression to end-stage renal disease), the onset of end
      stage renal disease and all-cause mortality in patients with type 2 diabetes when
      compared with standard care and amlodipine. OBJECTIVE: The present study assessed
      the cost effectiveness of irbesartan, an angiotensin II receptor antagonist, and
      amlodipine, a calcium channel blocker, in the treatment of Canadian patients with
      diabetic nephropathy and hypertension. METHODS: The analysis was conducted based
      on a Markov model using Monte Carlo simulation analysis to estimate the expected
      values for outcomes of interest. Transition probabilities were obtained from a
      comparative trial of amlodipine, irbesartan and standard care (antihypertensive
      treatment excluding other angiotensin II receptor antagonists or calcium channel
      blockers) in patients with overt diabetic nephropathy and hypertension. Canadian
      costs for the health states studied were obtained from published data. RESULTS:
      Based on the results of the Monte Carlo simulation, irbesartan was dominant over
      standard care and amlodipine because it both reduces costs and leads to greater
      life expectancy. The incremental cost-effectiveness ratio for amlodipine in
      comparison with standard care was 102,000 dollars. Estimates of net benefit were
      correlated with transition probabilities relating to progression from the initial
      health state. The results were insensitive to univariate sensitivity analysis.
      CONCLUSIONS: Irbesartan use would lead to a reduction in medical costs and an
      increase in life expectancy when compared with amlodipine or standard care.

PMID- 14968144
TI  - Secondary prevention after acute myocardial infarction in four Canadian
      provinces, 1997-2000.
AB  - BACKGROUND: Publication of population-based analyses of medication use after
      acute myocardial infarction (AMI) could encourage the use of effective secondary
      prevention medications. OBJECTIVE: To describe outpatient use of beta-blockers,
      angiotensin-converting enzyme (ACE) inhibitors, statins, calcium channel blockers
      and nitrates in elderly survivors of AMI over the fiscal years from 1997/98 to
      1999/2000 in Nova Scotia, Quebec, Ontario and British Columbia. METHODS: Linked
      administrative databases were used to identify all AMI patients 65 years of age
      or older admitted in Quebec (n=14,880), Ontario (n=28,647) and British Columbia
      (n=7549) over the study period, and to measure 90-day postdischarge utilization
      rates of cardiac medications for these patients. A population-based clinical
      registry was used to measure rates of prescription at discharge for elderly
      patients in Nova Scotia admitted to an acute care hospital from 1997 to 2000
      (n=1997). RESULTS: Utilization rates for beta-blockers, ACE inhibitors and
      statins increased over time, while rates for calcium channel blockers and
      nitrates decreased only slightly. The largest increases were for statins (Nova
      Scotia: 26% to 42%, Quebec: 27% to 43%; Ontario: 28% to 40%; British Columbia:
      30% to 42%) and for ACE inhibitors in Ontario (55% to 65%) and Nova Scotia (46%
      to 68%). Of the three drugs recommended for secondary prevention, overall
      utilization rates for beta-blockers were highest in Nova Scotia, lowest in
      British Columbia, and similar in Quebec and Ontario. Rates for ACE inhibitors
      were highest in Ontario and similar in Quebec, Nova Scotia and British Columbia.
      Rates for statins were slightly higher in Quebec and British Columbia than in
      Ontario and Nova Scotia. The proportion of patients without a prescription for
      any of the recommended drugs was highest in British Columbia (20%), lowest in
      Nova Scotia (8%), and similar in Quebec and Ontario (Ontario: 12%; Quebec: 13%).
      There was marked regional variation in utilization rates within the four
      provinces. CONCLUSIONS: Although utilization rates for recommended cardiac
      medications are increasing over time, there remains room for improvement. Overall
      utilization rates and temporal trends are generally similar in all four
      provinces, but there are wide regional variations within provinces.

PMID- 14968146
TI  - Volume and outcome of coronary artery bypass graft surgery: are more and less the
      same?
AB  - BACKGROUND: Despite the relatively high degree of regionalization of coronary
      artery bypass graft surgery in Canada, support is expressed for even further
      centralization of this procedure. The finding that the risk-adjusted mortality
      rate is lower at high volume hospitals is the basis for the decision to
      centralize. The goal of this study was to determine if current evidence supports
      the extension of such a policy. METHODS: A systematic review of the literature
      (1980 to 2002) provided mortality and surgical volume studies on 21 patient
      cohorts. For 16 of these, the published information permitted division of each
      cohort into those who had surgery at high or low volume hospitals. The target
      level for division was 200 cases per year; the level achieved was 200+/-44
      (mean+/-SD). The odds ratio (OR) was calculated from the observed and expected
      mortality ratios. In seven studies, volume had been treated as a continuous
      variable; the effect of volume was expressed as OR per 100 patients in four of
      these studies. RESULTS: A plot of OR against year of surgery showed a progressive
      increase from 0.55 (favouring high volume) in 1972 to 0.95+/-0.07 for the past
      few years. All estimates of OR per 100 patients were very close to 1.0, also
      indicating little or no effect of volume on mortality. INTERPRETATION: These
      results are compatible with the concept that with time the lower mortality
      associated with high volume has been virtually eliminated. It is hypothesized
      that this development is explained by a multifaceted learning curve, improved
      surgical training and technical advances. Therefore, the current evidence does
      not provide a basis for further regionalization of cardiac bypass surgery.

PMID- 14968147
TI  - Sarcoid heart disease.
AB  - BACKGROUND: Sarcoidosis is a multisystem inflammatory disease of unknown cause.
      Due to its protean and nonspecific clinical manifestations, the optimal
      diagnostic and therapeutic strategies, as well as prognosis, are not well
      defined. OBJECTIVE: To review the literature on sarcoid heart disease and present
      an approach to its diagnosis, prognosis and therapy. METHODS: MEDLINE and
      PreMEDLINE searches of all available English-language articles and case reports
      from 1966 to 2002 were performed. Search terms included 'sarcoidosis' and 'heart
      diseases', with a variety of medical subject subheadings. RESULTS: Clinical
      disease often includes heart block, dilated cardiomyopathy and ventricular
      arrhythmias. Patients with sarcoidosis are at increased risk of sudden death.
      Because the yield of endomyocardial biopsy for definitive diagnosis is low, the
      diagnosis is often made with a combination of electrocardiography, Holter
      monitoring, echocardiography, myocardial perfusion imaging and, most recently,
      magnetic resonance imaging. For symptomatic patients, medical therapy may include
      a trial of steroids and immunosuppressive therapy. Monoclonal antibodies against
      tumour necrosis factor may be employed in refractory cases. Heart block warrants
      a permanent pacemaker, while ventricular tachyarrhythmias are typically
      amiodarone-unresponsive, requiring implantation of an implantable cardioverter
      defibrillator. CONCLUSIONS: Although there are no large, randomized trial data on
      cardiac sarcoidosis, the literature suggests that making the diagnosis is
      clinically important. Unlike the situation in isolated pulmonary disease, cardiac
      involvement implies a poor prognosis. The diagnosis often requires high clinical
      suspicion with a combination of radiological and nuclear imaging. Therapy with
      steroids may halt progression of left ventricular dysfunction, while arrhythmias
      warrant device therapy.

PMID- 14968148
TI  - Le Reseau Quebecois de Cardiologie Tertiaire/Quebec Tertiary Cardiac Network.
AB  - The Tertiary Cardiac Network of Quebec (RQCT) was created in 2000. Its mission is
      to advise the Minister of Health on measures necessary to ensure that all
      patients have access to safe and quality services within recommended time frames.
      In 2002-2003, the cohort of patients needing a diagnostic catheterization totaled
      34,500. There were 14,000 angioplasties performed, a 54% increase over four
      years, and 7633 cardiac operations on adults, an 8% increase over the same four
      year period. The waiting lists, both for diagnostic catheterizations and surgery,
      are gradually decreasing. The RQCT is now a recognized partner to the other
      organizations to assure that the population has the proper access to care within
      the recommended time frame.

PMID- 14968150
TI  - Psychoneurophysiological assessment of recovery of cognitive function in patients
      with asthenia during rehabilitation.
AB  - Forty patients with severe asthenia were subjected to clinical, neurological,
      psychometric, and neurophysiologic examination before and after Enerion therapy.
      Psychoneurophysiological assessment with cognitive evoked potentials P300 and
      psychometric tests revealed serious impairment of cognitive functions in patients
      before therapy (compared to healthy individuals). Enerion therapy decreased the
      degree of psychoautonomic syndrome and asthenia and improved cognitive functions.

PMID- 14968151
TI  - Role of endothelium-dependent mechanism in formation of systemic hemodynamic
      responses to hypervolemia.
AB  - Blockade of NO synthesis in anesthetized rats significantly potentiated pressor
      responses to Polyglucin (by 70%) and considerably increased total peripheral
      resistance. It was concluded that vasodilatation induced by increased systemic
      blood flow (cardiac output) modulates pressor responses under conditions of
      increased blood volume.

PMID- 14968152
TI  - Effect of adrenalectomy on healing of indomethacin-induced gastric erosions in
      rats.
AB  - We studied the effects of adrenalectomy and replacement therapy on healing of
      gastric erosions in adult Sprague-Dawley rats developed 4 h after subcutaneous
      injection of indomethacin in a dose of 25 or 35 mg/kg. Adrenalectomy was
      performed 1 week before or 4 h after indomethacin administration. Healing was
      evaluated by changes in the area of erosions over 24 h after indomethacin
      administration at fixed time intervals. Plasma corticosterone was measured.
      Adrenalectomy (irrespective of the time of intervention) decelerated healing of
      gastric injuries. Injection of corticosterone in a physiological dose of 4 mg/kg
      at the initial stage of healing (4 h after indomethacin administration) improved
      healing of erosions.

PMID- 14968153
TI  - Parameters of neurocytes in vagal caudal ganglia innervating various organs of
      the gastrointestinal tract in rats.
AB  - We studied projections of various organs on afferent neurons of vagal caudal
      ganglia in mature albino rats. The morphometric parameters of labeled neurocytes
      were determined using computer-assisted image analysis system. It is established
      that somato- and viscerosensory neurocytes of vagal caudal ganglia in albino rats
      are characterized by specific shape and morphometric parameters.

PMID- 14968154
TI  - Glyprolines and semax prevent stress-induced microcirculatory disturbances in the
      mesentery.
AB  - One-hour immobilization stress considerably disturbed microcirculation in the
      mesentery: blood flow in small mesenteric vessels decreased or stopped and
      numerous hemorrhages appeared. Lymphatic vessels lost spontaneous activity and
      did not respond to norepinephrine. Administration of Semax and glyprolines 1 h
      before stress decreased the severity of stress-induced microcirculatory
      disturbances. PGP and GP were most effective in this respect.

PMID- 14968155
TI  - Pathophysiological aspects of experimental myocardial infarction during arterial
      hypertension.
AB  - We compared the results of clinical and experimental studies of endocrine
      parameters in patients with myocardial infarction and arterial hypertension and
      NISAG rats with hereditary stress-induced arterial hypertension during
      experimental myocardial infarction. Changes in the content of corticosterone,
      aldosterone, insulin, triiodothyronine, and thyroxin were similar in animals and
      patients with myocardial infarction and arterial hypertension. The disadaptive
      course of myocardial infarction against the background of arterial hypertension
      can be explained by reduced compensatory capacity of the myocardium.

PMID- 14968156
TI  - Immune system in vasopressin-deficient rats during ontogeny.
AB  - Morphofunctional immune disorders were revealed in vasopressin-deficient
      Brattleboro rats with diabetes insipidus during ontogeny. We observed a permanent
      decrease in the number of blood lymphocytes, increase in neutrophil count,
      reduced activity of macrophages, early involution of the thymus and spleen, and
      suppression of antibody production. These changes reflect impaired general
      resistance of these animals.

PMID- 14968157
TI  - Mouse lymphosarcomas sensitive and resistant to cyclophosphamide therapy:
      activity of cathepsins B, L, and D during various schemes of treatment with
      cyclophosphamide and SE-glycan.
AB  - We measured activities of cysteine (cathepsins B and L) and aspartyl proteinases
      (cathepsin D) in tumor tissue of mice with sensitive and resistant
      lymphosarcomas. In cyclophosphamide-resistant lymphosarcoma tissue activities of
      cathepsins B, L, and D were lower than in cyclophosphamide-sensitive
      lymphosarcoma. After treatment with cyclophosphamide in high doses enzyme
      activities in mice with cyclophosphamide-resistant lymphosarcoma increased more
      significantly than in animals with cyclophosphamide-sensitive lymphosarcoma.
      Sulfoethylated beta-1,3-D-glycan potentiated the effect of cyclophosphamide in
      mice with both forms of lymphosarcoma. This drug in the lowest dose (10 mg/kg)
      was most effective.

PMID- 14968158
TI  - Low-density lipoprotein subfractions during abdominal and gluteofemoral obesity.
AB  - Subfractional spectrum of plasma low-density lipoproteins in people with normal
      body weight and patient with obesity was studied by gradient electrophoresis (3
      12%) in polyacrylamide gel. Low-density lipoprotein subfractions in fasting
      patients with abdominal and gluteofemoral obesity were primarily presented by
      small particles (compared to people with normal body weight). The composition of
      low-density lipoprotein subfractions underwent most pronounced changes in
      patients with abdominal obesity after single fat load.

PMID- 14968159
TI  - Shielding effect of mineral schungite during electromagnetic irradiation of rats.
AB  - We studied the effect of nonthermal 37-GHz radiation on hemopoiesis in schungite
      shielded Wistar rats. Radiation with right-handed or left-handed rotation of the
      polarization plane of electromagnetic wave was used. Shielding with schungite
      decreased the severity of damage produced by high-frequency electromagnetic
      radiation.

PMID- 14968160
TI  - Combined action of doxorubicin and gestagens on doxorubicin-sensitive and
      doxorubicin-resistant MCF-7 cells.
AB  - The combined cytostatic effect of doxorubicin and gestagens progesterone,
      medroxyprogesterone acetate, mecigestone, and butagest on doxorubicin-resistant
      and doxorubicin-sensitive human breast cancer MCF-7 cells was studied by the MTT
      assay. On the 6th day of incubation progesterone, medroxyprogesterone acetate,
      mecigestone, and butagest in high concentrations (10(-5) M) potentiated the
      cytostatic action of doxorubicin in sensitive and resistant cells by 30-50%.
      Potentiation of the cytostatic effect produced by doxorubicin in sensitive cells
      is related to intrinsic cytotoxic activity of gestagens. In resistant cells these
      changes are associated with potentiation of the effect of doxorubicin.

PMID- 14968161
TI  - Comenic acid prevents post-stress enhancement of long-term potentiation in rat
      hippocampus.
AB  - In experiments on hippocampal slices from young rats subjected to immobilization
      cold stress we observed a pronounced increase in the amplitude of long-term
      potentiation of focal responses in CA1 area. Daily injections of comenic acid
      during stress exposure normalized parameters of long-term potentiation in the
      hippocampus.

PMID- 14968162
TI  - Neuromodulatory mechanism underlying the effect of the atypical dipeptide
      neuroleptic dilept.
AB  - We studied the effects of a new dipeptide neuroleptic Dilept (N-caproyl-L-prolyl
      L-tyrosine methyl ester) on activity of neurotransmitter systems in the brain.
      Dilept possessed antidopamine, glutamate modulatory, and cholinomimetic
      properties. These data indicate that Dilept is of potential efficacy in relieving
      positive and negative symptoms of schizophrenia.

PMID- 14968163
TI  - Anticoagulant activity of fucoidan from brown algae Fucus evanescens of the
      Okhotsk Sea.
AB  - In vitro and in vivo experiments showed that anticoagulant activity of sulfated
      polysaccharide from Fucus evanescens (brown algae of the Okhotsk Sea) was similar
      to that of heparin. Anticoagulant properties of fucoidan are determined by
      thrombin inhibition mediated via plasma antithrombin III.

PMID- 14968164
TI  - Comparative study of action mechanisms of dimebon and memantine on AMPA- and NMDA
      subtypes glutamate receptors in rat cerebral neurons.
AB  - Dimebon in low concentrations potentiated activity of AMPA-receptors in rat
      cerebellar Purkinje neurons, while memantine produced only an insignificant
      potentiation in a small group of these cells. In cortical neurons of rat brain
      memantine efficiently blocked NMDA-induced currents in dimebon-insensitive
      neurons. By contrast, its effect was far weaker in neurons, where the blocking
      action of dimebon on NMDA-receptors was most pronounced. It was hypothesized that
      the differences in the effects of memantine and dimebon are determined by their
      interaction with different sites of NMDA-receptors.

PMID- 14968165
TI  - Comparative ultrastructural study of the effect of imidazo-benzimidazole
      derivatives RU-185 and RU-254 on the development of microcirculatory disturbances
      in the skin under conditions of reduced blood flow.
AB  - In rats with experimental partial ischemia of the skin fold the state of
      microvessels and surrounding skin was studied by electron microscopy under
      control conditions and after treatment with imidazo-benzimidazole derivatives RU
      185 and RU-254. RU-185 was more potent than RU-254 in preventing the development
      of microcirculatory disturbances and altered permeability of capillary walls.

PMID- 14968166
TI  - Restriction fragments length polymorphism in the NAT1 gene of Europeans in West
      Siberia.
AB  - Restriction fragment length polymorphism in the NAT1 gene was assayed to reveal 7
      mutations (97C>T; 190C>T; 350,351G>C; 402T>C; 752A>T; D(1105); D(1025)) in 74
      Europeans from West Siberia. New methods for detecting mutations 350,351G>C,
      402T>C, 752A>T, D(1105), and D(1025) were proposed.

PMID- 14968167
TI  - Functional activity of P-glycoprotein in lymphocytes of patients with
      lymphoproliferative diseases.
AB  - Functional activity of P-glycoprotein in lymphocytes of patients with
      lymphoproliferative diseases was studied using rhodamine 123. Functional activity
      of P-glycoprotein in patients receiving a course of chemotherapy was lower than
      in controls. P-glycoprotein activity was higher in patients receiving more
      aggressive therapy. Initially activity of P-glycoprotein was higher in patients
      who did not respond to chemotherapy in comparison with those whose clinical
      status improved after a course of chemotherapy.

PMID- 14968168
TI  - Expression of estrogen receptors-beta and aromatase activity in primary mammary
      gland tumors.
AB  - Expression of estrogen receptors alpha and beta was studied by the PCR method in
      22 primary receptor-positive or receptor-negative breast carcinomas obtained
      during surgical intervention from patients aged 41-77 years and activity of
      aromatase in the same specimens was evaluated by the formation of tritiated water
      from labeled androgen precursor. Expression of estrogen receptors alpha and beta
      was more often detected in receptor-positive tumors characterized by lower
      aromatase activity. The authors conclude that the intensity of local production
      of estrogens can be one of the regulators of their expression, limiting this
      expression in case of more active production of estrogen in the tumor. On the
      other hand, there were no differences in the expression of estrogen beta-receptor
      gene or in detection of this receptor by immunocytochemical method in primary
      tumors lacking one of these receptors, and hence, this form of estrogen receptors
      is less involved in induction of progesterone receptors than alpha-receptors.

PMID- 14968169
TI  - Structure and properties of lipid bilayer of erythrocyte membranes in patients
      with malignant tumors.
AB  - The study of erythrocyte membranes in untreated patients with malignant tumors of
      different location (lung cancer, tumors of the head and neck, stomach and
      colorectal cancer) revealed changes in the fatty-acid spectrum of phospholipid
      fraction paralleled by an increase in the viscosity of the lipid bilayer,
      including the area of protein-lipid contacts. The degree of changes depended on
      tumor location.

PMID- 14968170
TI  - Role of matrix metalloproteinases 2 and 9 in determination of invasive potential
      of pancreatic tumors.
AB  - Our findings indicate that expression of matrix metalloproteinase-2 is an
      important prognostic marker of invasive potential of pancreatic tumors.
      Expression of this marker in neuroendocrine tumors (particularly in gastrinomas)
      can be used as a differential diagnostic criterion characterizing more malignant
      phenotype of tumors with the presence of ductal component. On the contrary, weak
      expression matrix metalloproteinase-9 is characteristic of less invasive
      phenotype of tumor cells (neuroendocrine and solid pseudopapillary tumors,
      mucinous cystadenomas). Co-expression of matrix metalloproteinases 2 and 9 is an
      unfavorable prognostic sign.

PMID- 14968171
TI  - Spatiotemporal characteristics of glycogen content in rat liver lobule.
AB  - We evaluated spatiotemporal characteristics of glycogen content in cells of rat
      liver lobule. Glycogen content in the liver lobule and its circulatory subzones
      underwent diurnal fluctuations with acrophase at 5.00. Spatial changes were
      characterized by a dependence of gradients in the lobule on the phase of diurnal
      rhythmic fluctuations. Total glycogen content in the peripheral subzone of the
      lobule 5.2-fold surpassed that in the central subzone. Our results illustrate
      spatiotemporal organization of glycogen content in the liver lobule.

PMID- 14968172
TI  - Two populations of miniature excitatory synaptic ionic currents in somatic muscle
      cells of Lumbricus terrestris earthworm body wall.
AB  - Three types of miniature excitatory synaptic currents were recorded in the same
      synaptic region of earthworm muscle cells: monoexponential (tau=1.2 msec) and
      biexponential (tau(1)=1.2 and tau(2)=8.0 msec). It was hypothesized that
      earthworm muscle cells contain at least two populations of acetylcholine
      sensitive ionic channels, which do not belong to classical nicotinic and
      muscarinic acetylcholine receptors.

PMID- 14968173
TI  - Effect of transplantation of fetal liver tissue on regenerative activity of
      hepatocytes in normal rats.
AB  - Regenerative activity of hepatocytes was studied in rats after transplantation of
      fetal liver tissue preexposed to low-intensity laser. Stimulation of the mitotic
      activity of hepatocytes by fetal liver tissue exposed to low-intensity laser is
      proven.

PMID- 14968174
TI  - Ultrastructural analysis of reorganization of the periodontium in simulated
      torsion abnormality and its correction with succinic acid.
AB  - Morphological study confirmed the positive effect of succinic acid on tissue
      ultrastructure, energy metabolism in cells of fibroblastic differon,
      reorganization and neogenesis of intercellular substance of the periodontal
      connective tissue during the retention period after correction of simulated
      dental torsion abnormality in dogs.

PMID- 14968175
TI  - Pathomorphological manifestations of antiocclusive factor in atherosclerotic
      obstruction of coronary arteries.
AB  - A total of 112 hearts with limited local dilatation zones in coronary arteries
      (antiocclusion factor) selected from 500 patients dead from chronic forms of
      coronary heart disease were studied by postmortem contrast polypositional
      coronarography and cardiometry. A relationship between antiocclusion factor, on
      the one hand, and coronary artery stenosis and degree of vascularization of the
      left ventricular wall, on the other, was shown. The adaptation role of
      antiocclusion factor in coronary blood flow disorders caused by atherosclerotic
      obstruction (stenosis, occlusion, thrombosis) of the major coronary arteries was
      demonstrated. The incidence of antiocclusion factor in individual segments of
      coronary arteries depending on the type of atherosclerotic involvement and index
      of myocardial blood supply was determined.

PMID- 14968176
TI  - New diagnostic potentialities of cardiorespiratory synchronization in children.
AB  - The study demonstrated that the method of cardiorespiratory synchronization
      provides valuable information on the nature of arrhythmia and helps to evaluate
      the regulatory adaptive potentialities of a child. The width of synchronization
      range and the latency of synchronization at the lower boundary are the indicators
      of regulatory adaptive potentialities.

PMID- 14968177
TI  - Evaluation of nonspecific brain systems in patients with panic disorders by the
      method of P300 cognitive evoked potentials.
AB  - Measuring of the amplitude of auditory cognitive evoked potentials P300 showed
      its changes (decrease and increase) in patients with panic disorders compared to
      healthy individuals. The authors hypothesize that the decrease in P300 amplitude
      reflects increased activity of the cerebral reticulothalamic structures, while
      its increase is associated with activation of the septohippocampal limbic system
      in patients with panic disorders. P300 recording can serve as a valuable
      diagnostic method.

PMID- 14968178
TI  - A method for modeling obturation of extrahepatic bile ducts.
AB  - A model of extrahepatic bile duct obturation was developed in experiment on rats.

PMID- 14968179
TI  - A method for introducing human blood leukocytes in cold anabiosis at -50 degrees
      Celsius.
AB  - We propose a simple, effective, and economic method for introducing human blood
      leukocytes in cold anabiosis at moderately low temperature (-50 degrees Celsius).

PMID- 14968180
TI  - Photocompression study of tissue blood flow.
AB  - Non-pulsed optical density of the small intestine was studied in 32 dogs and the
      results were compared with the data of angiotensometry and pulsomotorography. New
      regularities of blood circulation in the small intestine were detected: more than
      half of the total volume specific blood flow in the intestinal tissue is normally
      realized in vessels at a pressure below 40 mm Hg. An additional criterion of
      viability of the small intestine during ischemia is developed.

PMID- 14968182
TI  - Research in the WHO Eastern Mediterranean region. Where do we stand.

PMID- 14968183
TI  - How can developing countries succeed in biomedical journalism?

PMID- 14968184
TI  - Experience of King Abdul-Aziz City for science and technology in funding medical
      research in Saudi Arabia.
AB  - Funding scientific research is important for accelerating the progress of science
      and technology, to fulfill the development objectives of the country. King Abdul
      Aziz City for Science and Technology (KACST) was established in 1977 to support
      and promote applied scientific research and coordinate the activities of the
      scientific research institutions and centers in line with requirements of
      development plans of the Kingdom. King Abdul-Aziz City for Science and Technology
      also cooperates with other concerned institutions in formulating strategies and
      national policies for the development of science and technology. King Abdul-Aziz
      City for Science and Technology has started several research grants programs,
      which include; Annual General Grants Program, National Grants Program, Limited
      Grants Program, Humanities Grants Program, Graduate Students Grants Program and
      Production Sectors Grants Program for the promotion of science and technology in
      the Kingdom. The process of funding follows a systematic scientific mechanism
      based on predetermined research priorities. Selection of the research proposals
      is accomplished on the basis of strict scientific criteria. The funding of
      medical research projects is considered most important among all scientific
      fields, as these are related to human health. The medical field is classified
      into specific sub fields constituting the major branches of medicine. Since 1979,
      KACST has funded 430 medical research projects at an estimated cost of 185.9
      million Saudi Riyals representing approximately 31.2% of the grants total
      funding. King Abdul-Aziz City for Science and Technology puts much emphasis on
      publishing results obtained from the research projects through different
      channels. Seven hundred and thirty-eight scientific papers have been published in
      all fields whereas 243 research papers out of them are in the medical field. This
      paper highlights the establishment, aims and tasks associated with KACST. Also,
      the paper reviews research funding by KACST grants programs with a focus on
      funded medical research projects and publications of research papers originating
      from different funded projects.

PMID- 14968185
TI  - Editing and publishing of a medical journal. Success of an unconventional
      workflow.
AB  - Regional journals often face constraints that threaten their growth, calling for
      novel coping strategies. This paper outlines the problems and challenges in
      editing and publishing the SQU Journal for Scientific Research: Medical Sciences,
      the only peer-reviewed medical journal in the Sultanate of Oman. These included
      the absence of secretarial support and the consequent need to reduce paperwork,
      the fact that most papers required substantial editing even after peer review,
      and the lack of a single workflow for creating documents for the press and the
      Internet. These challenges were successfully met by creating an unconventional
      all-electronic workflow that catered to both the print and the online versions.
      The paper describes this workflow and offers suggestions for journals wishing to
      streamline theirs.

PMID- 14968186
TI  - Quality of medical journals with special reference to the Eastern Mediterranean
      Health Journal.
AB  - Medical journals will continue as a main vehicle of scientific information for
      years to come, particularly where access to more efficient instruments is
      relatively limited. The quality of medical journals depends on several factors
      involving 3 groups of people; namely: the authors, the reviewers and the editors.
      The Eastern Mediterranean Health Journal (EMHJ) formulated its essential
      requirements for the manuscripts submitted for possible publication. These are
      published in every issue of the Journal, and potential authors are strongly
      advised to adhere to them, to avoid first-hand rejection of their progress. The
      reviewers' role is a keystone in maintaining the quality of a medical journal. A
      reviewer is required to address several important aspects of the paper under
      review and to resend his opinion thereon with his recommendation concerning the
      acceptability of the paper or otherwise. The editorial management is a crucial
      part of the publishing process. The editors begin action with the receipt of the
      manuscript, direct the various steps of evaluation, correction and re-submission,
      until an editorial decision is taken to accept the paper as is, accept it after
      modification or rejection. Editors will then make necessary text and layout
      editing. Due consideration is given to the statistical, multilingual and ethical
      aspects as well as to the overall uniformity of the terminology, nomenclatures
      and style throughout the volume as a whole. In February 1999, the EMHJ was
      accepted by the National Library of Medicine, USA, to be indexed and included in
      Index Medicus and MEDLINE. Such selection usually depends on several critical
      criteria; namely: scope and coverage, quality of content, quality of editorial
      work, production quality, audience and types of content. Evidently, the EMHJ has
      satisfactorily met all the above criteria.

PMID- 14968187
TI  - Problems faced by editors of peer reviewed medical journals.
AB  - Forty-six medical and dental journals are published from Pakistan of which only
      29 are currently recognized by the Pakistan Medical and Dental Council. Only a
      few are peer reviewed. Six are indexed in Medline while EMBASE Excerpta Medica
      and World Health Organization Index Medicus for Eastern Mediterranean Region
      cover others. Editors of the peer reviewed medical journals are faced with
      numerous problems, which relate to the authors. Some of these are: shortage of
      quality of manuscripts, poor quality of reviewers, problems with indexation in
      international indexing services particularly Medline, duplicate submission and
      authorship and lastly, financial problems. Patronage from the Pharma industry is
      the major source of revenue which itself has serious implications. Editing a
      medical journal is a very stressful job and the editors have to work under too
      many pressures. A lot of useful data is presented at medical conferences, but a
      vast majority of it remains unpublished for various reasons, which adversely
      affects the citation rate from scientists from the developing third world
      countries in the world of medical literature. A few lectures on medical writing
      and research methodology to final year medical students will expose them to the
      art of medical writing. Specialty organizations can be persuaded to have a
      session on medical writing at their conferences, which will be extremely helpful
      not only to the potential new authors but also others, thereby improving the
      quality of their manuscripts. In addition to regular seminars, workshops for
      authors, reviewers and training courses for editors, subscribing to local medical
      journals by healthcare professionals and libraries are some of the measures that
      will help improve the situation to a great extent.

PMID- 14968188
TI  - Translating medical journals into Arabic. JAMA Middle East as an example.
AB  - JAMA Middle East has distributed monthly 25,000 issues into 14 Arab countries
      since 1991. Translating the original articles into Arabic was considered as the
      license permits translation. The number of Arab physicians exceeds 250,000, but
      those who studied medicine in Arabic are very few. Adequate translators and other
      publishing staff are lacking. Advertisers will not invest in journals without
      readership. The other 13 international editions of JAMA publish in their national
      languages, so do their medical schools. Teaching medicine in a foreign language
      did not bring leadership to Arab medicine. It is just another indicator of Arab
      underdevelopment. There is growing support to shift the language of medical
      teaching into Arabic, but the only practical step has been the Unified Medical
      Dictionary.

PMID- 14968189
TI  - Views of Iranian medical journal editors on medical research publication.
AB  - OBJECTIVE: Medical journal editors play an important role in optimizing research
      publication. This study evaluates the views of Iranian medical journal editors,
      and their knowledge of medical publication standards. METHODS: In May 2001, 51
      editors from all journals approved by the Ministry of Health were invited to
      participate, 27 of whom completed the study. A self-administered questionnaire,
      based on the Uniform Requirements for Manuscripts Submitted to Biomedical
      Journals (URMS) was used which consisted of 28 questions in 9 subject fields.
      These fields included: peer review, conflicts of interest, authorship criteria,
      publication ethics, duplicate publication, mass media, advertising, competing
      manuscripts, and the Internet. The knowledge of the editors was assessed by a
      scoring system, with a range of -46 to +44 points. RESULTS: Twenty-three of the
      participants were editors-in-chief and 4 were managing editors. Their average age
      was 47.3 +/- 8.7 years and 25 were male. All journals were peer-reviewed, most
      having 2 or 3 reviewers for each manuscript. Of the journals, 92.6% accepted or
      rejected an article on the basis of the views of most reviewers and 52%,
      sometimes or always, used a statistician as a reviewer. Most of the editors
      believed that writing the first draft and designing the study are authorship
      criteria, and most of them believed that these 2 are stated in URMS. Seven
      journals (25.9%) never published advertisements. Among journals that sold
      advertisements, the most popular policy (85%) was the rejection of advertisements
      because they advertised harmful products. Out of 27 journals, 12 were accessible
      on the Internet, and 7 had independent websites. Of the editors, 81.5% thought
      that a website is useful for their journal. The average knowledge score of the
      editors was 6.5 +/- 7.5. None had a negative score, 33% scored zero, 45% obtained
      average scores and 22% obtained good scores. CONCLUSION: The results show that
      peer review is favored by all the editors studied, though it seems that journals
      do not follow clear-cut policies in this regard. Most of the editors, agreed with
      the statements of URMS to some extent and generally most have average to high
      knowledge of URMS.

PMID- 14968205
TI  - The cytokine TNF-alpha. Genetics and suitability for prenatal risks assessment.
AB  - The tumor necrosis factor (TNF-alpha) is a cytokine known as a mediator of
      inflammation and immunity. The genes coding the tumor necrosis factors alpha and
      beta are considered part of class III major histocompatability complex. The 2
      involved genes have been mapped to chromosome 6. Certain mutations in the TNF
      alpha gene are believed to be causative for increased production of the cytokine.
      In this respect, the most common variant is the TNF2 allele, a single nucleotide
      substitution of guanine by adenine at position -308 relative to the promoter
      transcription site of the gene. Elevated production of TNF-alpha has been found
      to be associated with several infectious diseases including malaria. Elevated
      levels of TNF-alpha have also been observed to associate with increased risk of
      preterm delivery, chorioamnionitis and fetal morbidity including encephalopathy.
      The present article reviews the genetics of the cytokine TNF-alpha and discusses
      its suitability as a candidate marker for assessment of increased risk of preterm
      delivery and fetal morbidity.

PMID- 14968206
TI  - Fertility preservation in children and young adults undergoing treatment for
      malignancy.
AB  - Advances in cancer therapy have improved the long-term survival of young patients
      suffering from malignancies. However, the adverse effects of the treatment are
      sterility and loss of gonadal function especially in females. Preservation of
      fertility in males by sperm freezing is more practical and already established.
      For young women undergoing cancer treatment, the availability of preserving the
      gonadal function and fertility has just begun. Today, we can cryopreserve the
      oocytes, the embryos or the ovarian tissue and in those undergoing pelvic
      irradiation, laparoscopic lateral ovarian suspension can be considered. Because
      women with non-gynecological malignancies seek advice from a general surgeon or a
      medical oncologist, increasing the awareness of the physicians and general public
      is recommended.

PMID- 14968207
TI  - Evaluation of disability of occupational illness claims for workers'
      compensation.
AB  - Occupational physicians are faced with the challenge of estimating the
      contribution of occupational and non-occupational risk factors to a particular
      work-related illness for workers' compensation. This paper proposes guidelines
      for occupational physicians to evaluate claims for presentation to a compensation
      board. Occupational bladder cancer was taken as an example. Relevant literature
      was obtained and reviewed. A worksheet was designed to record pertinent
      information on occupational illness. The procedure for handling a claim is
      described. Failure to follow such an approach may lead to gross inequities.

PMID- 14968208
TI  - Knowledge, attitudes and intention of high school students towards the nursing
      profession in Riyadh city, Saudi Arabia.
AB  - OBJECTIVE: To determine the knowledge, attitudes, and intention among the Saudi
      high school students towards the nursing profession. In addition, the study aims
      to identify students' perception of causes preventing them to become nurses. It
      also aims to determine the factors influencing the Saudi high school students'
      choice of nursing profession. METHODS: We used the descriptive analytical
      research design. Stratified random sampling procedures were employed to represent
      the Saudi high school students, 3 male and 3 female schools scattered in all
      areas of Riyadh city were selected. A total of 600 questionnaires were
      distributed and 503 questionnaires were returned, of which, 479 questionnaires
      were valid for analysis (79.8% response rate). The data collection started from
      November 2002 to January 2003. Descriptive and inferential statistics were used
      to analyze the collected data. RESULTS: High school students scored a reasonable
      level on the knowledge dimension, but did not achieve high scores on the attitude
      dimension, however, they achieved very low scores on the intention of being a
      nurse in the future (5.2% of them indicated nursing as their preferred future
      job). Inferential data analysis showed that attitude, having or not having a
      nurse friend and knowledge was found to have significant positive influence on
      high school students' intention, while long working hours and high work load
      compared to other jobs were found to have a significant negative influence.
      CONCLUSION: Results indicated that the more knowledge and positive attitude on
      nursing, the more likely the student would be attracted to the nursing
      profession. Accordingly, it could be concluded that Saudi health decision-makers
      need to increase the positive attitude on the nature and encouraging
      characteristics of modern nursing and its increasing respect as a skillful career
      for high school students. Reconsideration of salaries and benefits were
      recommended in order to attract more students to the nursing profession.

PMID- 14968209
TI  - Cytotoxic effects of some animal and vegetable extracts and some chemicals on
      liver and colon carcinoma and myosarcoma.
AB  - OBJECTIVE: To study, the cytotoxic effects of some biological and chemical agents
      on G1, S, G2, M and G0 phases of liver and colon carcinomas and myosarcoma cells
      obtained with chemical carcinogens dimethylbenzanthracene (DMBA) and cadmium
      chloride. METHODS: Eight rabbit livers, colon carcinoma and myosarcoma cell lines
      were obtained by injection of DMBA in the Biology Laboratory, of the University
      of Dumlupinar, Kutahya, Turkey between January 2001 and June 2003. All lines were
      grown at 37 degrees celsius and 5% carbon dioxide in sterile RPMI-1640 medium
      with 10% fetal bovine serum after addition of glutamate, penicillin (50 units/ml)
      and streptomycin (50 ug/ml) (complete medium). Cells were grown on standard
      tissue culture plastic flasks to 80% confluence and passed by trypsinization.
      RESULTS: Tortoise (Testudo graeca) shell, sponge (Geodia cydonium), medusa
      (Aurelia aurita), meat flies (Calliphora erythrocephala) larva, frog (Rana
      ridibunda) larva and juniper (Juniperus communis) berry extracts killed a large
      amount of the liver and colon carcinomas and the myosarcoma cells in G2, M and G0
      phases (p<0.01). The mistletoe (Viscum album) extract had more effect in only the
      G0 phase (p<0.05). Genistein, genistin, glycitein, glycitin, daitzein and daitzin
      have significantly decreased in the cancer cells tests, particularly, genistein
      and daitzein caused the apoptotic effect in G2, M and G0 phases (p<0.01). Cesium
      chloride, a mixture of cesium chloride with magnesium chloride had the most
      effect on tumor cells (p<0.01). AzhexSi, Azhex-AzhepSi, Et-Azhex-AzhepSi,
      AzhepSi, Hexamine and DL 54 have been inhibited in various levels of the cancer
      cells (p<0.05, p<0.01). CONCLUSION: This data suggest that some biological
      extracts and chemicals tested may be useful chemotherapeutic agents to inhibit
      the growth of cancer cells. This study sheds some light for new anti cancerogenic
      experiments preventing various cancers on humans.

PMID- 14968210
TI  - Spectrum of malignant lymphomas in Bahrain. Leitmotif of a regional pattern.
AB  - OBJECTIVE: To determine the clinicopathologic features of malignant lymphomas in
      Bahraini patients. METHODS: A retrospective hospital-based study was conducted.
      All new cases of malignant lymphoma diagnosed during the period January 1996 to
      December 2001 at the Salmaniya Medical Complex in Bahrain were included in the
      study. RESULTS: Seventy-two cases met the inclusion criteria. This included 24
      (33.3%) cases of Hodgkin's disease (HD) and 48 (66.7%) cases of Non-Hodgkin
      lymphomas (NHL). A young age at presentation (median 20 years) mixed cellularity
      histology, lack of extra nodal involvement and rare marrow involvement
      characterized HD. The majority of NHL showed diffuse high or intermediate grade
      lesions. A high number of primary extra nodal neoplasms (41.7% of NHL) and
      frequent involvement of the gastrointestinal tract with Helicobacter pylori
      associated gastric lymphomas were notable features among NHL cases.
      Immunohistochemical staining in 30 cases showed 26 cases (86.7%) of B cell and 4
      cases of T cell origin. CONCLUSION: The study highlights common features that
      distinguish malignant lymphoma reported from countries of the Arabian Gulf
      region. This pattern distinguishes them from the disease encountered in the
      Western world.

PMID- 14968211
TI  - Comparison of some risk factors between non-familial and familial breast cancer
      females in Jordan.
AB  - OBJECTIVE: To compare the risk factors such as age, menopause, menarche, age at
      the first pregnancy, number of pregnancies and breast feeding period between the
      familial and non-familial breast cancer females in Jordan. METHODS: This study
      was carried out in Al-Basheer Hospital, Amman, Jordan during the period 2000 and
      2002. A questionnaire was used to collect information from 99 females who were
      histologically and pathologically diagnosed with breast cancer. Data of the
      questionnaire were entered and analyzed using statistical package for social
      sciences. RESULTS: The highest percentage of non-familial and familial breast
      cancer occurrence was among age group 51-60 years. The age of the first pregnancy
      is another risk factor of which the highest percentage of breast cancer was
      reported for both familial (57.1%) and non-familial (65.4) breast cancer females
      who have their first pregnancy while they were 20-years-old and above. More than
      4 pregnancies also represents a risk factor for both non-familial (67.9%) and
      familial (68.6%) breast cancer patients. In this study, there are no statistical
      differences between menopause and menarche age among the breast cancer females.
      Finally, an inverse relationship was shown between breast feeding period (equal
      or more than 24 months) and the occurrence of breast cancer in both non-familial
      (2%) and familial (0%) breast cancer. CONCLUSION: This study found that age 51-60
      years and the increase number of pregnancies (more than 4) in the age of 20 years
      or more are risk factors for both types of breast cancer. On the other hand,
      longer period of breast feeding (more than 24 months) decreases the risk of
      breast cancer in both types.

PMID- 14968212
TI  - Saphenofemoral ligation as a safe and effective alternative for the treatment of
      chronic venous leg ulcer.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of isolated saphenofemoral
      junction ligation for the treatment of chronic venous leg ulcer in comparison to
      traditional stripping procedure. METHODS: Thirty six patients (28 men and 8
      women) with mean age of 42.3 +/- 8.7, presented with a venous leg ulcer. After
      taking a full history, they underwent examination for presence of edema,
      cellulitis or local ulcer infection. The site and size of ulceration were
      recorded and ankle-brachial pressure index (ABPI) was measured. Venous color
      Doppler ultrasonography was performed and venous valvular incompetence was
      assessed using Valsalva test and calf compression. Patients were divided into 2
      groups. Group I, (n=10) assigned for long saphenous stripping, while group II,
      (n=26) assigned for saphenofemoral ligation and divided combined with ligation of
      major tributaries under local infiltration anesthesia. Mean operative time,
      postoperative complications and hospital stay were recorded. The study was
      carried out in Benha University Hospital, Egypt and Armed Forces Hospital, Khamis
      Mushayt, Southern Region, Kingdom of Saudi Arabia, between January 2000 and
      December 2001. RESULTS: The mean operative time and the hospital stay were
      significantly (p<0.05) reduced in group II compared to group I. The postoperative
      complications were significantly (x2=7.5, p<0.05) reduced in group II. Ulcer
      healing started after 3 months in group II and 6 months in group I, but, by 12
      months, group II had a significant (x2=6.7, p<0.05) number of healed ulcers
      (n=22, 84.6%), compared to group I (n=7, 70%). CONCLUSION: The isolated ligation
      of saphenofemoral junction is a minimally invasive, safe and effective modality
      for treatment of chronic leg ulcer, and being easily performed under local
      anesthesia and considered to be a satisfactory procedure for treatment of leg
      ulcer in patients who are unfit for general anesthesia.

PMID- 14968213
TI  - Branching pattern of the left coronary artery and an important branch. The median
      artery.
AB  - OBJECTIVE: This study was performed to assess the variations in the branching
      pattern and diameters of the terminal branches of the left coronary artery and
      discuss various names given to the third branch. METHODS: Hearts of 21 autopsies
      and 19 cadavers were fixed with 10% formalin and their coronary arteries were
      examined by dissecting the epicardium. The dissections were performed at the
      Anatomy Departments of Faculties of Medicine, Ankara and Hacettepe Universities,
      Ankara, and Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul,
      Turkey, between April 2001 and June 2003. RESULTS: There were 2 branches in 19
      hearts, 3 branches in 19 hearts, 4 branches in one heart and 5 branches in
      another. Diameter and length of these vessels are noted. CONCLUSION: Upon
      examination of the diameters and important variations of the branches of the left
      coronary artery, the importance of the median artery has been noted. Various
      names given to this artery in the literature should be replaced with the name
      "median artery".

PMID- 14968214
TI  - Endocarditis prophylaxis in children with congenital heart disease. A parent's
      awareness.
AB  - OBJECTIVE: The aim of this study is to determine the parental knowledge of
      bacterial endocarditis prophylaxis (BEP). METHODS: Parents of 205 patients
      attending the Pediatric Cardiology Clinics at King Khalid University Hospital,
      Riyadh, King Fahad University Hospital, Al-Khobar and Prince Sultan Cardiac
      Center, Riyadh, Kingdom of Saudi Arabia from July 1999 to June 2000, were
      interviewed by a standard questionnaire pertaining to their knowledge of their
      child's cardiac disease, medications, and BEP. The patients' cardiac lesions and
      current medications were verified by a review of medical records. Each patient's
      need for BEP was determined according to American Heart Association
      recommendations. RESULTS: All parents answered the interview questions. The
      patients' mean age was 5 years and 8 months with a range of one month to 15
      years. One hundred and two (50%) parents were high school graduates. Fifty-two
      (25%) parents correctly defined endocarditis. Two hundred and one (98%) parents
      knew the correct name of their child's cardiac condition, and 46/50 (92%) of
      those on medication knew the names of their child's current medications. Only
      113/176 (64%) parents with at risk children were aware of measures to prevent
      endocarditis. CONCLUSION: While most parents know the name of their child's heart
      lesion and current medications, parental knowledge of endocarditis and BEP was
      limited. Intensified education and awareness programs are needed in order to
      prevent potential major morbidity and mortality for pediatric patients with
      congenital heart disease.

PMID- 14968215
TI  - Alpha-1 antitrypsin phenotypes in patients with lung, prostate and breast cancer.
AB  - OBJECTIVE: Determination of Alpha1-antitrypsin (alpha1-AT) phenotypes in
      Jordanian patients with lung, prostate and breast cancer to find a prevalent
      phenotype that could be recommended for the early diagnosis of cancer. METHODS:
      This study was conducted at Jordan University of Science and Technology, Irbid,
      Jordan, during the period May 2001 to May 2002. Alpha1-AT phenotypes for 83
      Jordanian cancer patients distributed as follows, 25 lung cancer, 25 prostate
      cancer and 33 with breast cancer, were tested using isoelectric focusing gel
      electrophoresis and immunofixation techniques. RESULTS: Isoelectric focusing
      results demonstrated that 96% of lung cancer patients were of PiMM phenotype and
      4% of PiFM phenotype. All prostate cancer patients (100%) were found to be of
      PiMM phenotype. Phenotypes of breast cancer patients were 94% PiMM, 3% PiFM and
      3% PiMS. CONCLUSION: These findings demonstrated that there were no significant
      differences in the distribution of alpha1-AT phenotypes among Jordanian patients
      with lung, prostate and breast cancer and they matched those reported for healthy
      individuals. Thus, we cannot recommend a given alpha1-AT phenotype for early
      diagnosis of the above mentioned types of cancer.

PMID- 14968216
TI  - Non-invasive positive pressure ventilation in acute respiratory failure. An
      alternative modality to invasive ventilation at a general hospital.
AB  - OBJECTIVE: Non-invasive positive pressure ventilation (NPPV) is a relatively new
      modality of managing acute respiratory failure (ARF). It has not been applied
      before in our area. The aim of this study is to verify the use of NPPV on
      patients with ARF at a general hospital level. METHODS: All patients admitted at
      the Al-Amiri Hospital, Kuwait (a secondary medical center) between 1999 and 2001
      with ARF and met the inclusion criteria were included in the study. The non
      invasive mode of nasal ventilation was used as the respiratory support. RESULTS:
      A total of 21 patients were included in the final analysis. The major cause of
      ARF type 2 was chronic obstructive pulmonary disease (COPD) in 71%. The overall
      success rate of NPPV trials was 71.4%. In the successful trials of ARF type 2,
      the arterial blood gas parameters of PaCo2 (p<0.005), pH (p=0.023), and PaO2
      (p<0.001) showed improvement from the first hour of intervention. Analysis of
      variance with repeated measurement for the arterial blood gas variables showed
      statistical significance of changes in favor of NPPV during initial close
      monitoring with p<0.001. The percentage of successful trials at the general wards
      was 82% versus 67% for the intensive care unit cases (ICU). Surprisingly, failure
      of trials related mainly to the clinical status of the patients. CONCLUSION: Non
      invasive positive pressure ventilation is an effective ventilatory support in ARF
      in a proper clinical setting. It may be used safely in the general hospital
      outside the ICU.

PMID- 14968217
TI  - Clinical measurement of proprioceptive function after anterior cruciate ligament
      reconstruction.
AB  - OBJECTIVE: Proprioception is very important for the integrity and stability of
      the knee joint. Patients with anterior cruciate ligament (ACL) tear have a
      decline in proprioceptive functions of the injured knee. However, improvement of
      proprioceptive functions of the knee after ACL reconstruction is a subject of
      considerable debate. This study was conducted to evaluate the results of a simple
      clinical proprioception test developed by the author in patients with ACL
      reconstructed knees. METHODS: This study was conducted in King Fahd Hospital of
      the University, Al-Khobar, Kingdom of Saudi Arabia, from January 1996 to June
      2002. The proprioceptive function of the knee joint was studied in a group of ACL
      reconstructed patients (n=22) and compared them with a group of ACL deficient
      patients (n=32) and a group of healthy controls (n=30). Proprioception was
      evaluated based on the performance in a simple clinical test. RESULTS: There was
      a significant difference in proprioceptive functions between the ACL deficient
      knees and the ACL reconstructed group (p<0.05), but there was no significant
      difference between the ACL reconstructed and the normal control group (p>0.05).
      CONCLUSION: These findings indicate that proprioceptive deficits in ACL deficient
      knees, as measured clinically using the described test, might improve after ACL
      reconstruction.

PMID- 14968219
TI  - Prevalence of hepatitis C virus among bilharziasis patients.
AB  - OBJECTIVE: Hepatitis C virus (HCV) infection with concurrent Schistosoma mansoni
      infestation has emerged as a major cause of chronic liver disease and liver
      cirrhosis. The aim of this study was to investigate the prevalence of HCV among
      bilharzia patients. METHODS: The study was conducted at the Viral Diagnostic and
      Parasitology Departments, Regional Laboratory and Blood Bank, Dammam, Kingdom of
      Saudi Arabia from August 1999 to July 2000. Sera from a total of 405 patients,
      including 356 Saudi nationals and 49 non-Saudis, who had a clinical suspicion of
      bilharziasis were tested, using enzyme linked immunosorbent assay for HCV
      infection and indirect hemagglutination tests for Schistosoma infestation.
      Diagnosis of schistosomiasis was made when serum anti-schistosoma antibody titer
      was either equal to or more than 1:256. RESULTS: A total of 39 cases out of 405
      tested positive for bilharzia antibodies comprising of 22 (44.9%) non-Saudi and
      17 (4.8%) Saudi individuals. Among these patients 7(17.9%) were found to have
      evidence of HCV infection. Of the 7 patients tested positive for HCV antibodies,
      there were 4 (26.7%) Egyptians, 2 (11.8%) Saudis and one (14.3%) Middle-Eastern.
      CONCLUSION: Our data shows that a good proportion (17.9%) of patients with
      bilharziasis had HCV infection. The percentage positive for HCV antibody were
      26.7% in Egyptians, which is higher when compared to other nationals and Saudis.

PMID- 14968218
TI  - Effect of diclofenac alone or in combination with alpha-tocopherol on the
      oxidative activity of polymorphonuclear leukocytes in healthy and osteoarthritic
      individuals.
AB  - OBJECTIVE: To investigate the effects of diclofenac alone or when combined with
      alpha-tocopherol on the oxidative activity of polymorphonuclear leukocytes (PMNs)
      in healthy and osteoarthritic (OA) patients. METHODS: The study was carried out
      at the College of Medicine, King Saud University, Riyadh, Kingdom of Saudi
      Arabia, over the period 1999 to 2000. Twelve healthy controls and 12
      osteoarthritic patients were recruited to the study. Twelve healthy controls and
      osteoarthritic patients were given diclofenac 50 mg thrice daily orally,
      initially for 5 days then alpha-tocopherol at 200 mg thrice daily orally, was
      added for another 5 days. Blood samples were drawn before the start of the study
      (pre-treatment) and at 5 days following treatment with diclofenac alone and 10
      days following treatment with diclofenac and alpha-tocopherol. Chemiluminescence
      (CL) response was measured for whole blood and isolated polymorphonuclear
      leukocytes (PMNs) on all samples. RESULTS: Diclofenac enhanced CL response of
      whole blood and of PMNs of healthy controls when stimulated with phorbol
      myristate acetate (PMA) and opsonized zymosan (OPZ). Co-treatment with alpha
      tocopherol resulted in no appreciable change in the CL response of whole blood
      when stimulated with PMA or OPZ but a further significant enhancement of CL
      response of isolated PMNs when these cells were stimulated by either PMA or OPZ.
      In osteoarthritic patients, diclofenac alone and when combined with alpha
      tocopherol showed no significant change in CL response of whole blood. The CL
      response of PMNs from OA patients was decreased by diclofenac alone. However,
      this inhibitory effect was not observed when alpha-tocopherol was used together
      with diclofenac. CONCLUSION: The effect of diclofenac alone or in combination
      with alpha-tocopherol did not produce a consistent effect on the CL response of
      whole blood or isolated PMNs of healthy or osteoarthritic patients.

PMID- 14968220
TI  - The effect of glycemic control in type 2 diabetic patients with diabetes-related
      dyslipidemia.
AB  - OBJECTIVE: The study was planned to investigate whether the serum lipid profile
      in type 2 diabetes mellitus was different between groups of patients classified
      as having good, satisfactory or poor glycemic controls, depending on their serum
      fructosamine levels. METHODS: The study was carried out in the Department of
      Laboratory, Dammam College for Health Sciences, Dammam, Kingdom of Saudi Arabia
      between February 2003 to June 2003. Clinical laboratory data from diagnosed type
      2 diabetic patients were used in the study. One hundred and nineteen patient's
      data were randomly selected, and according to their serum fructosamine levels,
      the patients were divided into 3 groups: 29 patients classified as patients with
      good glycemic control (GGC) with serum fructosamine level <250 micromol/L, 44
      patients classified as satisfactory glycemic control (SGC) with serum
      fructosamine level ranging between 250-355 micromol/L and 46 patients classified
      as poor glycemic control (PGC) with serum fructosamine >355 micromol/L. The
      fasting serum glucose and various lipids and lipoprotein concentrations of each
      group were analyzed by one way analysis of variance and regression analysis.
      RESULTS: In the PGC group, the serum total cholesterol (6.11+/- 1.56 mmol/l),
      triglyceride (2.13 +/- 0.71 mmol/L) and very low density lipoprotein-cholesterol
      (1.09 +/- 0.40 mmol/L) concentrations were significantly higher than that of the
      SGC (5.59 +/- 0.89, 1.59 +/- 0.38 and 0.86 +/- 0.28 mmol/L,), and the GGC (5.11
      +/- 1.06, 1.25 +/- 0.32 and 0.78 +/- 0.29 mmol/L), whereas, those of the SGC were
      slightly raised, but not statistically significant, compared to the GGC. The high
      density lipoprotein cholesterol was significantly lower, and the low density
      lipoprotein cholesterol was elevated in both satisfactory and poorly controlled
      groups compared to good control group. Significant correlations were evident
      between the serum fructosamine and glucose concentrations (r=0.79, p<0.0001), and
      between them as independent parameters and the serum lipid concentrations.
      CONCLUSION: The glycemic control in type 2 diabetes significantly improves
      diabetic related dyslipidemia, and would be expected to reduce the risk of
      atherosclerosis. It is also worth mentioning that the serum fructosamine measure
      gives a good index for the glycemic control, and its value can reflect the
      profile of serum lipids.

PMID- 14968221
TI  - Leptin level in pregnant mothers at term and cord blood and the effect of
      newborns gender.
AB  - OBJECTIVE: To evaluate the leptin level in healthy pregnant mothers at term and
      in their newborns and its relationship to their body mass index (BMI) and gender
      of the newborn. METHODS: The leptin level was measured in serum of 187 pregnant
      women at term delivering at the King Khalid University Hospital, Riyadh, Kingdom
      of Saudi Arabia in July 2001 and their newborns. Correlation studies were made
      between leptin level and their growth parameters, and gender of the newborns.
      RESULTS: Leptin level of the mothers was significantly higher compared to their
      newborns. There was a significant correlation between leptin level in the
      pregnant women and their weight, BMI, and the newborns leptin level and weight,
      but not their height or BMI. A statistically significant difference was found
      between male and female newborns plasma leptin level. A significant correlation
      was found between male newborns leptin level and all their growth parameters,
      while in the female newborns there was no correlation between their leptin level
      and BMI. CONCLUSION: Leptin plays an important role in providing a growth
      promoting signal during pregnancy, but the fat mass does not seem to be the most
      important predictor of cord leptin level.

PMID- 14968222
TI  - Cigarette smoking behavior among male secondary school students in the Central
      region of Saudi Arabia.
AB  - OBJECTIVE: This study was conducted to examine the smoking habits among male
      secondary school students in Al-Qassim, Kingdom of Saudi Arabia (KSA) and to
      assess their knowledge and attitudes towards smoking. METHODS: This cross
      sectional study was conducted in Al-Qassim region, KSA during March 2003.
      Randomly selected was 14 out of 110 government male secondary schools. In the
      sample section, care was taken to represent urban and rural communities. In urban
      areas, 8 schools with the largest number of students were selected. This is in
      addition to 3 schools, which were the only schools with special education on
      Islamic, Commercial and Technical programs. In the rural areas the 3 most distant
      schools were included in the sample. Data were obtained through self-administered
      questionnaires that contained questions on personal background, smoking behavior,
      knowledge and attitude towards cigarette smoking. A total of 2203 students
      responded to the questionnaires with 83% response rate. RESULTS: Of the studied
      group, 606 (29.8%) were current smokers and among these 83.7% started smoking at
      the age of 15 years or less. Technical and commercial secondary school students
      had higher prevalence of the habit of smoking than those in general and Islamic
      secondary schools. It was found that the more pocket money received by the
      students, the higher was the prevalence of smoking. The most common reason given
      for cigarette smoking behavior (CSB) was the influence of friends (63.5%). Family
      factor, especially the brother's smoking habit (24.8%) was also important. Most
      of the students knew that smoking is harmful to their own health (89.3%), and to
      others (73.9%). The association between smoking and lung cancer was 84.3%, 80.9%
      for chest disease and 78.2% for heart disease, while the relation to other
      diseases was less known. CONCLUSION: We conclude that onset of smoking in the
      young is alarming. This is of immense importance in formulating health education
      strategies, which should be directed towards pupils, teachers and parents. The
      religious aspect should also be an integral part of such programs.

PMID- 14968223
TI  - Spontaneous bladder rupture in a non-augmented neuropathic bladder.
AB  - A spontaneous bladder rupture in an intact bladder without history of trauma has
      been reported before with different postulation for the pathogenesis. All these
      cases were reported in the adult age group. Patients with a neuropathic bladder
      associated with such a complication were post augmentation cystoplasty or
      catheter induced injury. We present our experience in a boy with a neuropathic
      bladder secondary to spina bifida who had a spontaneous bladder rupture with no
      surgical intervention carried out before, and discuss the possible pathogenesis.

PMID- 14968224
TI  - Susacs syndrome.
AB  - We describe a 25-year-old woman that presented with frequent rotational
      dizziness, visual loss of the right eye one month later, and unilateral deafness
      one year after. After 2 years, she presented with a right hemiparesis and
      deafness greater for low frequency tones. Magnetic resonance imaging with
      angiography of the brain showed constriction in the first segment of the cerebral
      anterior artery diagnosed as Susac's syndrome.

PMID- 14968225
TI  - Portal vein thrombosis after splenectomy for beta-thalassemia major.
AB  - Portal vein thrombosis is a recognized complication after splenectomy in beta
      thalassemia major due to the chronic hypercoagulable state which has been
      recognized to exist in childhood thalassemia and contribute to thromboembolic
      events. We are reporting one patient with beta-thalassemia major developed portal
      vein thrombosis following splenectomy.

PMID- 14968226
TI  - Primary actinomycosis of the abdominal wall.
AB  - Primary actinomycosis of the abdominal wall is a rare clinical entity. Only 7
      adequately described cases have been reported in the English literature. We
      report a case of isolated abdominal wall actinomycosis involving the left lower
      quadrant of the abdominal wall in a 32-year-old diabetic male. The diagnosis was
      confirmed by histopathological examination. Surgical drainage of the abscess
      followed by long-term administration of penicillin resulted in cure. The
      clinicopathological spectrum of actinomycosis is reviewed and isolated
      involvement of the abdominal wall is characterized in light of the knowledge
      acquired from the available literature on this rare clinical presentation. The
      significance of obtaining tissues for culture and histopathology in all
      inflammatory lesions is emphasized.

PMID- 14968227
TI  - Katayama syndrome.
AB  - Two schoolboys from a non-endemic region visited an endemic area of
      Schistosomiasis in Yemen. They developed cutaneous itching after swimming in
      infected ponds. Five weeks later both brothers were admitted to the hospital with
      high fever, abdominal pain, vomiting and diarrhea. The blood results exhibited
      marked eosinophilia and schistosomal serological test showed an evidence of
      exposure. Initially, stool examinations were negative, but the sigmoidoscopy was
      suggestive for acute bilharzial colitis and the biopsy showed schistosoma ova; a
      finding consistent with Katayama syndrome. Both patients treated with
      Praziquantel, and they became asymptomatic, and the eosinophilia normalized. This
      report shows the importance of endoscopic and histological examination in
      suspected acute colonic schistosomiasis, which allows early treatment and avoids
      possible complications.

PMID- 14968228
TI  - Laparoscopic cholecystectomy in a pregnant lady with systemic lupus
      erythematosus.

PMID- 14968229
TI  - Aggressive malignant abdominal mesothelioma.

PMID- 14968230
TI  - Complications of femoral venous catheterization in critically ill patients.

PMID- 14968231
TI  - Perinatal mortality rate in a teaching hospital in Sudan. Review of 15 years.

PMID- 14968232
TI  - Age at menarche in Jordanian girls.

PMID- 14968233
TI  - Barbexaclone use in pregnancy.

PMID- 14968234
TI  - No evidence of persistent helicobacter pylori infection in peripheral blood of
      patients with coronary heart disease.

PMID- 14968235
TI  - Suicide after treatment of chloroquine-resistant falciparum malaria with quinine.

PMID- 14968236
TI  - Cyclopia.

PMID- 14968237
TI  - Physical assault on a medical resident.

PMID- 14968256
TI  - Resistance to disuse atrophy in a turtle hindlimb muscle.
AB  - The purpose of this study was to characterize the changes in a turtle hindlimb
      muscle (external gastrocnemius) after exposure to three conditions of disuse:
      immobilization, tenotomy, and spinalization. Histochemical analysis and
      measurement of muscle fiber cross-sectional area and weighted cross-sectional
      area were used to assess the potential conversion of muscle fiber types and
      changes in fiber size. It was found that unlike its counterpart in mammalian
      endotherms, the external gastrocnemius muscle of the adult turtle, Trachemys
      scripta elegans, was remarkably resistant to each model of reduced muscle
      function. It is suggested that such resistance to disuse is due to intrinsic
      mechanisms that enable heterothermic mammals and ectothermic vertebrates to
      tolerate an unfavorable climate and food and water shortages by using
      hypometabolic states.

PMID- 14968257
TI  - Pulmonary embolism findings on chest radiographs and multislice spiral CT.
AB  - Multislice spiral CT is becoming an increasingly important tool for diagnosing
      pulmonary embolism. However, in many instances, a chest radiograph is usually
      performed as a first-line examination. Many parenchymal, vascular, and other
      ancillary findings may be observed on both imaging modalities with a highly
      detailed depiction of abnormalities on multislice CT. A comprehensive review of
      chest radiograph findings is presented with side-by-side correlations of CT
      images reformatted mainly in the frontal plane.

PMID- 14968258
TI  - Lateral torticollis on plain radiographs and MRI: Grisel syndrome.

PMID- 14968259
TI  - Caveats when interpreting intravenous urograms following ileal orthotopic bladder
      substitution.
AB  - The aim of this study was to evaluate the appearance of the upper urinary tract
      following cystectomy and ileal orthotopic bladder substitution. Intravenous
      urograms (IVUs) performed preoperatively and at regular intervals postoperatively
      on 87 long-term survivors (minimum survival, 5 years) following ileal orthotopic
      bladder substitution were reviewed. Distention of the collecting system with
      blunted or rounded fornices was defined as dilatation. If in addition contrast
      medium excretion was delayed on the 5-min film, this was defined as obstruction.
      Collecting system dilatation was present on all IVU films obtained from most
      patients (80%) within 6 months of surgery, even in the absence of urinary tract
      obstruction. In contrast, dilatation was commonly seen only on the 20-min
      postinjection films (79%) on urograms performed more than 1 year following
      surgery, but not encountered on the other two postinjection radiographs (at 5 and
      60 min). Five years after surgery, permanent obstruction was observed in only
      five (3%) renoureteral units. Dilatation of the upper urinary tract after ileal
      orthotopic bladder substitution is a frequent finding on the 5-min, 20-min, and
      60-min films during the early postoperative period but is found only on the 20
      min film 1 year and later after surgery. These findings should not be
      overinterpreted as obstruction.

PMID- 14968260
TI  - Dose reduction in skeletal and chest radiography using a large-area flat-panel
      detector based on amorphous silicon and thallium-doped cesium iodide: technical
      background, basic image quality parameters, and review of the literature.
AB  - The two most frequently performed diagnostic X-ray examinations are those of the
      extremities and of the chest. Thus, dose reduction in the field of conventional
      skeletal and chest radiography is an important issue and there is a need to
      reduce man-made ionizing radiation. The large-area flat-panel detector based on
      amorphous silicon and thallium-doped cesium iodide provides a significant
      reduction of radiation dose in skeletal and chest radiography compared with
      traditional imaging systems. This article describes the technical background and
      basic image quality parameters of this 43 x 43-cm digital system, and summarizes
      the available literature (years 2000-2003) concerning dose reduction in
      experimental and clinical studies. Due to its high detective quantum efficiency
      and dynamic range compared with traditional screen-film systems, a dose reduction
      of up to 50% is possible without loss of image quality.

PMID- 14968261
TI  - MRI findings in acute cerebellitis.
AB  - Acute cerebellitis is an inflammatory process involving the cerebellum. We report
      the clinical, CT and MRI features of four cases and a review of the literature.
      Bilateral diffuse hemispheric abnormalities represent the most common imaging
      presentations. Our observations demonstrate the various imaging appearances of
      acute cerebellitis. Simultaneous involvement of both hemispheres and the vermis
      has not been reported previously. The development of cerebellar atrophy following
      an initial normal MR imaging examination is also a new finding. In atypical
      clinical presentation, MR imaging can lead to the diagnosis. MR imaging findings
      have, however, no prognostic value.

PMID- 14968262
TI  - MR-based full-body preventative cardiovascular and tumor imaging: technique and
      preliminary experience.
AB  - Recent improvements in hardware and software, lack of side effects, as well as
      diagnostic accuracy make magnetic resonance imaging a natural candidate for
      preventative imaging. Thus, the purpose of the study was to evaluate the
      feasibility of a comprehensive 60-min MR-based screening examination in healthy
      volunteers and a limited number of patients with known target disease. In ten
      healthy volunteers (7 men, 3 women; mean age, 32.4 years) and five patients (4
      men, 1 woman; mean age, 56.2 years) with proven target disease we evaluated the
      performance of a comprehensive MR screening strategy by combining well
      established organ-based MR examination components encompassing the brain, the
      arterial system, the heart, the lungs, and the colon. All ten volunteers and five
      patients tolerated the comprehensive MR examination well. The mean in-room time
      was 63 min. In one volunteer, insufficient colonic cleansing on the part of the
      volunteer diminished the diagnostic reliability of MR colonography. All remaining
      components of the comprehensive MR examination were considered diagnostic in all
      volunteers and patients. In the five patients, the examination revealed the known
      pathologies [aneurysm of the anterior communicating artery ( n=1), renal artery
      stenosis ( n=1), myocardial infarct ( n=1), and colonic polyp ( n=2)]. The
      outlined MR screening strategy encompassing the brain, the arterial system, the
      heart, the lung, and the colon is feasible. Further studies have to show that MR
      based screening programs are cost-effective in terms of the life-years saved.

PMID- 14968264
TI  - Left gluteal focal myositis in a patient with signet ring adenocarcinoma of the
      stomach: not a paraneoplastic phenomenon.
AB  - Focal myositis, the much rarer clinical and pathological variant of polymyositis,
      is generally a benign inflammatory pseudotumor of skeletal muscle Thus far, only
      three cases have been reported in association with a neoplasm. We now describe a
      fourth case of localized gluteal myositis seen in a case of signet ring
      adenocarcinoma of the stomach occurring not as a paraneoplastic syndrome, as in
      the previously reported three cases, but as an immunoinflammatory response around
      metastatic cell foci in both the involved muscles and local lymphatics.

PMID- 14968265
TI  - Anatomic variations of the hepatic arteries in 604 selective celiac and superior
      mesenteric angiographies.
AB  - In modern surgical and transplantation procedures the recognition of anatomic
      vascular abnormalities of the hepatic arteries is of greater importance than
      ever. The purpose of this study was to evaluate and classify these variations
      with respect to their impact on visceral surgery. A total of 604 selective celiac
      and superior mesenteric angiographies performed on patients with known or
      suspected liver cirrhosis or hepatic or pancreatic malignancies and on donors of
      partial liver grafts were analyzed retrospectively. The vascular anatomy of the
      liver was classified according to different established systems and with
      particular attention to rare variations. Hepatic arterial anatomy as considered
      normal in textbook descriptions was found in 79.1%, an aberrant or accessory left
      hepatic artery (LHA) arising from the left gastric artery in 3.0% and an aberrant
      or accessory right hepatic artery (RHA) branching off the superior mesenteric
      artery in 11.9% of the cases. In 1.4% of the cases there was a combination of
      anomalies of both the LHA and RHA. Variants of the celiac trunk, double hepatic
      arteries branching at the celiac trunk or hepatic arteries arising directly from
      the aorta, occurred in 4.1% of the cases. Further atypical branches of the LHA
      and RHA were found in 0.5% of the cases. Since the incidence and pattern of
      different types of hepatic arterial anatomy can require specialized preoperative
      diagnostic as well as intraoperative strategies, knowledge of these abnormalities
      and their frequency is of major importance for the surgeon as well as the
      radiologist.

PMID- 14968266
TI  - Percutaneous plating of distal tibial fractures.
AB  - We studied 20 patients (mean age 47.9+/-3.9, range 25-85 years) undergoing
      percutaneous plating of the distal tibia for 43A or 43C fractures in the period
      1999-2002. Bony and functional results were classified into four categories
      ranging from excellent to poor. Union was achieved in all but one patient. Seven
      patients had angular deformities between 7 and 10 degrees, but none of these
      patients required further operations. No patient had a leg-length discrepancy
      greater than 1 cm. Thirteen patients had excellent and good bone results, and
      none used walking aids. Seven patients reported stiffness of the operated ankle.
      This reported use of percutaneous techniques in the management of fractures of
      the distal tibial metaphysis is preliminary. However, the functional results and
      the lack of soft tissue complications are encouraging.

PMID- 14968267
TI  - A single major chromosomal region controls natural killer cell-like activity in
      rainbow trout.
AB  - We report the identification of a single major chromosomal region controlling
      natural killer (NK) cell-like activity in rainbow trout (Oncorhynchus mykiss). A
      genetic map based on 484 AFLP and 39 microsatellite genotypes from 106 doubled
      haploid fish was constructed. These fish were produced by androgenesis from a
      hybrid of two clonal lines divergent in NK-like activity. NK-like activities for
      75 of the doubled haploids were quantified by an in vitro chromium release assay
      utilizing (51)Cr-labeled YAC-1 target cells. Composite interval mapping revealed
      a single major quantitative trait locus (QTL) associated with NK-like activity in
      this rainbow trout model. Genetic mapping revealed this QTL to also be unlinked
      to: fragmented MHC class I and MHC class II regions, the leukocyte receptor
      cluster, the natural killer cell enhancement factor ( NKEF) gene, the RAG-1 gene,
      and two QTL associated with resistance to infectious pancreatic necrosis virus in
      rainbow trout. Collectively, these results extend the utility of rainbow trout as
      an immunological model and are consistent with the idea that a single chromosomal
      region homologous to the natural killer cell complex (NKC) located on syntenic
      portions of mouse chromosome (Chr) 6, human Chr 12, and rat Chr 4 may exist in a
      lower vertebrate model.

PMID- 14968263
TI  - Comparative analysis of 5,211 leaf ESTs of wild rice (Oryza minuta).
AB  - The expressed sequence tags (ESTs) presented in this report are the first
      transcriptomes of wild rice. A cDNA library was constructed from 4-week-old leaf
      samples of greenhouse-grown Oryza minuta. The 5,211 cDNA clones of O. minuta
      represent 3,401 unique sequences, consisting of 2,787 singletons and 614
      assembled sequences. Database comparisons of the cDNAs in GenBank's non-redundant
      databases using BLAST revealed that 4,957 of the 5,211 cDNAs (95.1%) showed a
      high degree of sequence homology to genes from other organisms. Most of the
      transcripts identified were genes related to metabolism, energy, protein
      biosynthesis and subcellular localization. The metabolism and energy categories
      of the O. minuta ESTs showed a considerably higher gene expression level than
      those of O. sativa ESTs. These data and genes can be utilized in rice breeding.

PMID- 14968268
TI  - Characterization of novel ascidian beta integrins as primitive complement
      receptor subunits.
AB  - Integrin-type complement receptors play pivotal roles in the effector mechanisms
      of the complement system. Previously, we identified an integrin alpha subunit,
      alpha(Hr1), from the solitary ascidian, Halocynthia roretzi, which is involved in
      the complement-dependent phagocytic activities of ascidian hemocytes. To identify
      integrin beta subunits that pair with alpha(Hr1) to compose ascidian complement
      receptors, genes encoding beta subunits were cloned and characterized for their
      binding property to alpha(Hr1). Using degenerate primers and RT-PCR, two integrin
      beta transcripts (beta(Hr1) and beta(Hr2)) were isolated from H. roretzi hemocyte
      total RNA and the entire coding sequences of both cDNA species were determined.
      The putative primary structure of each ascidian gene product retained domains
      characteristic for integrin beta subunits. Phylogenetic analysis revealed that
      beta(Hr1) and beta(Hr2) are located outside of vertebrate integrin beta groups,
      comprising an independent cluster specific for the ascidian lineage. The
      alpha(Hr1), beta(Hr1) and beta(Hr2) subunits all showed hemocyte-specific
      expression on Northern blot analysis, and recombinant proteins of both beta
      subunits could bind to alpha(Hr1) on insect cells. The beta(Hr1) subunit was
      expressed especially on the surface of ascidian phagocytic hemocytes, such as
      phago-amoebocytes. In the immunoprecipitation analysis of ascidian hemocytes
      using anti-beta(Hr1) antiserum, alpha(Hr1) was coprecipitated with beta(Hr1).
      These observations showed that beta(Hr1), and possibly beta(Hr2) too, binds to
      alpha(Hr1) to comprise integrin molecules on ascidian hemocytes, which act as
      ancestral forms of complement receptors in the primitive complement system of
      ascidians.

PMID- 14968269
TI  - Radiation dose in vertebroplasty.
AB  - We wished to measure the absorbed radiation dose during fluoroscopically
      controlled vertebroplasty and to assess the possibility of deterministic
      radiation effects to the operator. The dose was measured in 11 consecutive
      procedures using thermoluminescent ring dosimeters on the hand of the operator
      and electronic dosimeters inside and outside of the operator's lead apron. We
      found doses of 0.022-3.256 mGy outside and 0.01-0.47 mGy inside the lead apron.
      Doses on the hand were higher, 0.5-8.5 mGy. This preliminary study indicates
      greater exposure to the operator's hands than expected from traditional apron
      measurements.

PMID- 14968270
TI  - Socio-economic inequalities in first-time use of antidepressants: a population
      based study.
AB  - OBJECTIVE: To analyse whether first-time use of antidepressants (incidence) and
      selection of TCAs (tricyclic antidepressants) versus new-generation drugs are
      associated with socio-economic status and psychiatric history. METHOD: We
      conducted a population-based cohort study using registry data covering Funen
      County, Denmark. A total of 305,953 adult residents without antidepressant
      prescriptions 5 years prior to the study period (1998) were included. RESULTS:
      The 1-year incidence rate of antidepressant prescription (1.7%) increased with
      age. It was higher in people who were female, less educated, unemployed, those
      receiving old-age or disability pension, low-income groups, and singles. The
      proportion prescribed new-generation antidepressants (82%) showed no difference
      according to socio-economic variables (education, annual income and socio
      economic group), but was higher among the young and single. Admission to
      psychiatric hospital within 4 years prior to the study period was associated with
      high-incidence rate of antidepressant prescription and overall a preference for
      the new-generation antidepressants. CONCLUSION: Socio-economic status did not
      seem to influence the selection of TCAs versus new-generation antidepressants.
      Compatible with the general epidemiology of depression, low socio-economic status
      was associated with a high number of first-time users of antidepressants in the
      population, and the incidence rate increased with age.

PMID- 14968271
TI  - Cortical activation following a balance disturbance.
AB  - Although recent work suggests that cortical processing can be involved in the
      control of balance responses, the central mechanisms involved in these reactions
      remain unclear. We presently investigated the characteristics of scalp-recorded
      perturbation-evoked responses (PERs) following a balance disturbance. Eight young
      adults stabilized an inverted pendulum using their ankle musculature while
      seated. When perturbations were applied to the pendulum, subjects were instructed
      to return (active condition) or not return (passive condition) the pendulum to
      its original stable position. Primary measures included peak latency and
      amplitude of early PERs (the first negative peak between 100 and 150 ms, N1),
      amplitude of late PERs (between 200 and 400 ms) and onset and initial amplitude
      of ankle muscle responses. Based on the timing of PERs, we hypothesized that N1
      would represent sensory processing of the balance disturbance and that late PERs
      would be linked to the sensorimotor processing of balance corrections. Our
      results revealed that N1 was maximal over frontal-central electrode sites (FCz
      and Cz). Average N1 measures at FCz, Cz, and CPz were comparable between active
      and passive tasks ( p>0.05). In contrast, the amplitude of late PERs at Cz was
      less positive for the active condition than for the passive ( p<0.05). The
      similarity in N1 between tasks suggests a sensory representation of early PERs.
      Differences in late PERs may represent sensorimotor processing related to the
      execution of balance responses.

PMID- 14968272
TI  - Differential effects of blinks on horizontal saccade and smooth pursuit
      initiation in humans.
AB  - Blinks executed during eye movements affect kinetic eye movement parameters,
      e.g., peak velocity of saccades is decreased, their duration is increased, but
      their amplitude is not altered. This effect is mainly explained by the decreased
      activity of premotor neurons in the brainstem: omni-pause neurons (OPN) in the
      nucleus raphe interpositus. Previous studies examined the immediate effect of
      blinks directly on eye movements but not their effect when they are elicited
      several hundred milliseconds before the eye movements. In order to address this
      question we tested blinks elicited before the target onset of saccades and
      pursuit and compared the results to the gap effect: if a fixation light is
      extinguished for several hundred milliseconds, the reaction time (latency) for
      subsequent saccades or smooth pursuit eye movements is decreased. Monocular eye
      and lid movements were recorded in nine healthy subjects using the scleral search
      coil system. Laser stimuli were front-projected onto a tangent screen in front of
      the subjects. Horizontal step-ramp smooth pursuit of 20 deg/s was elicited in one
      session, or 5 deg horizontal visually guided saccades in another experimental
      session. In one-third of the trials (smooth pursuit or saccades) the fixation
      light was extinguished for 200 ms before stimulus onset (gap condition), and in
      another third of the trials reflexive blinks were elicited by a short airpuff
      before the stimulus onset (blink condition). The last third of the trials served
      as controls (control condition). Stimulus direction and the three conditions were
      randomized for saccades and smooth pursuit separately. The latency of the step
      ramp smooth pursuit in the blink condition was found to be decreased by 10 ms,
      which was less than in the gap condition (38 ms). However, the initial
      acceleration and steady-state velocity of smooth pursuit did not differ in the
      three conditions. In contrast, the latency of the saccades in the gap condition
      was decreased by 39 ms, but not in the blink condition. Saccade amplitude, peak
      velocity, and duration were not different in the three conditions. There was also
      no difference in blink amplitude and duration of pupil occlusion in the blink
      condition, neither in saccades nor in smooth pursuit. The latency reduction of
      smooth pursuit, but not of saccades, may neither be explained by the brief pupil
      occlusion nor by visual suppression, warning signals, or the startle response.
      Whether the effects are caused by the influence of blinks on OPNs or other
      premotor structures remains to be tested.

PMID- 14968273
TI  - Quickly tapping targets that are flashed during smooth pursuit reveals perceptual
      mislocalisations.
AB  - In various studies subjects have been shown to misperceive the positions of
      targets that are flashed during pursuit eye movements. They mislocalise them in
      the direction of pursuit. Nevertheless, Hansen (1979) found that subjects
      accurately hit targets that are flashed during pursuit with a quick hammer blow.
      We examined whether this is because there is a fundamental difference between the
      information that determines our perceptual judgements of a target's position and
      the information that is used to guide our hand to a similar target. Subjects were
      asked to quickly tap targets that were flashed during pursuit with their index
      finger. They systematically tapped ahead of the position of the flash, in
      accordance with the above-mentioned perceptual mislocalisations. Thus the lack of
      systematic errors in Hansen's study is not a general property of fast motor
      responses.

PMID- 14968274
TI  - The role of plantar cutaneous sensation in unperturbed stance.
AB  - Considerable evidence shows that sensation from the feet and ankles is important
      for standing balance control. It remains unclear, however, to what extent
      specific foot and ankle sensory systems are involved. This study focused on the
      role of plantar cutaneous sensation in quasi-static balance control.
      Iontophoretic delivery of anesthesia was used to reduce the sensitivity of the
      forefoot soles. In a follow-up experiment, subjects received intradermal
      injections of local anesthetic into the entire weight-bearing surface of the foot
      soles. Properties of the center-of-foot-pressure (COP) trajectories and ground
      reaction shear forces were analyzed using stabilogram-diffusion analysis and
      summary statistics. Effects of foot-sole anesthesia were generally small and
      mostly manifested as increases in COP velocity. Magnitude of COP displacement was
      unaffected by foot-sole anesthesia. Forefoot anesthesia mainly influenced
      mediolateral posture control, whereas complete foot-sole anesthesia had an impact
      on anteroposterior control. During bipedal stance, statistically significant
      effects of foot-sole anesthesia on COP were present only under eyes-closed
      conditions and included increases in COP velocity (11-12%) and shear force root
      mean-square (13%), the latter indicating increases in body center-of-mass
      accelerations due to the foot-sole anesthesia. Similar effects were seen for
      unipedal stance in addition to an increase in anteroposterior COP median
      frequency (36%). Changes in stabilogram-diffusion parameters were confined to the
      short-term region suggesting that sensory information from the foot soles is
      mainly used to set a relevant background muscle activity for a given posture and
      support surface characteristic, and consequently is of little importance for
      feedback control during unperturbed stance. In general, this study demonstrates
      that plantar sensation is of moderate importance for the maintenance of normal
      standing balance when the postural control system is challenged by unipedal
      stance or by closing of the eyes. The impact of reduced plantar sensitivity on
      postural control is expected to increase with the loss of additional sensory
      modalities such as the concomitant proprioceptive deficits commonly associated
      with peripheral neuropathies.

PMID- 14968275
TI  - Task goal and grip force dynamics.
AB  - This study examined the effect of task goal on the structure of isometric force
      variability during precision grasping. In general, variability of isometric force
      production decreases when participants are asked to maintain a particular force
      output and are provided with visual feedback, although the irregularity of force
      output tends to increase under these conditions. In the current study we compared
      the tasks of holding an object using a precision grip and holding an object using
      a precision grip while matching a force target. Adults held an object between the
      index finger and thumb and force output was measured using load cells. The mass
      (92, 276, 460 g) and the grip aperture (5.5 and 8.5 cm) of the object were varied
      producing six different object conditions. The goal of the task was to either:
      (a) hold the object comfortably in a stable position (holding task) or (b) hold
      the object comfortably in a stable position while maintaining a constant target
      force level that matched the grip force of the holding condition (target task).
      The results showed that the amount of force variability in the target condition
      was lower than during the holding condition, while the force output was more
      regular in the holding condition. Increments in object mass increased force
      regularity in the holding condition whereas increments of force level decreased
      regularity in the target condition. The level of coherence between the two digits
      was very high (approximately 0.98) and maximum coherence occurred at a higher
      frequency during the target (0.94 Hz) as opposed to the holding (0.70 Hz)
      condition. The findings reveal that the goal of the task can qualitatively change
      the dynamical organization of the force output in prehension, even when the
      average force level produced is the same. This effect on the control strategy was
      mediated by visual information processes that interact with level of force output
      in determining the structure of variability. Theorizing about the organization of
      isometric force output should include the effects of task goals as well as the
      level of force per se.

PMID- 14968276
TI  - Target-dependent differences between free and constrained arm movements in
      chronic hemiparesis.
AB  - This study compares the kinematic and kinetic characteristics of constrained and
      free upper limb movements in eight subjects with chronic hemiparesis. Movements
      of the dominant and nondominant limbs were also examined in five control
      subjects. Rapid movements were performed in the horizontal plane from a central
      starting point to five targets located to require various combinations of
      flexion/extension rotations at the elbow and shoulder. Support of the upper limb
      against gravity loading was provided either by a low-friction air-bearing
      apparatus (constrained condition) or by voluntary generation of abduction and
      external rotation torques at the shoulder (free condition). Data analysis focused
      on the peak joint torques generated during the acceleratory phase of movement,
      and on the net change in joint angles at the elbow and shoulder. We found that
      movement parameters were broadly invariant with support condition for either limb
      of control subjects, as well as for the nonparetic limb of hemiparetic subjects.
      In contrast, support condition had a target-dependent effect on movements of the
      paretic limb. Relative to the constrained condition, peak torques for free arm
      movements were significantly reduced for distal targets requiring elbow extension
      and/or shoulder flexion torques. However, peak elbow flexion and shoulder
      extension joint torques for proximal targets were relatively unaffected by
      support condition. Of perhaps more functional importance, free movements were
      characterized by a target-dependent restriction in the hand's work area that
      reflected a reduced range of active elbow extension, relative to constrained
      movements. The target-dependent effects of support condition on movements of the
      paretic limb are consistent with the existence of abnormal constraints on muscle
      activation patterns in subjects with chronic hemiparesis, namely an abnormal
      linkage between activation of the elbow flexors and shoulder extensors,
      abductors, and external rotators.

PMID- 14968277
TI  - Is perception of upper body orientation based on the inertia tensor? Normogravity
      versus microgravity conditions.
AB  - During lateral leg raising, a synergistic inclination of the supporting leg and
      trunk in the opposite direction to the leg movement is performed in order to
      preserve equilibrium. As first hypothesized by Pagano and Turvey (J Exp Psychol
      Hum Percept Perform, 1995, 21:1070-1087), the perception of limb orientation
      could be based on the orientation of the limb's inertia tensor. The purpose of
      this study was thus to explore whether the final upper body orientation (trunk
      inclination relative to vertical) depends on changes in the trunk inertia tensor.
      We imposed a loading condition, with total mass of 4 kg added to the subject's
      trunk in either a symmetrical or asymmetrical configuration. This changed the
      orientation of the trunk inertia tensor while keeping the total trunk mass
      constant. In order to separate any effects of the inertia tensor from the effects
      of gravitational torque, the experiment was carried out in normo- and
      microgravity. The results indicated that in normogravity the same final upper
      body orientation was maintained irrespective of the loading condition. In
      microgravity, regardless of loading conditions the same (but different from the
      normogravity) orientation of the upper body was achieved through different joint
      organizations: two joints (the hip and ankle joints of the supporting leg) in the
      asymmetrical loading condition, and one (hip) in the symmetrical loading
      condition. In order to determine whether the different orientations of the
      inertia tensor were perceived during the movement, the interjoint coordination
      was quantified by performing a principal components analysis (PCA) on the
      supporting and moving hips and on the supporting ankle joints. It was expected
      that different loading conditions would modify the principal component of the
      PCA. In normogravity, asymmetrical loading decreased the coupling between joints,
      while in microgravity a strong coupling was preserved whatever the loading
      condition. It was concluded that the trunk inertia tensor did not play a role
      during the lateral leg raising task because in spite of the absence of
      gravitational torque the final upper body orientation and the interjoint coupling
      were not influenced.

PMID- 14968278
TI  - Effects of combined cortical and acoustic stimuli on muscle activity.
AB  - Hitherto, it has proven difficult to investigate interactions between cerebral
      and brainstem motor systems in the human. We hypothesised that transcranial
      magnetic stimulation (TMS) centred over the dorsal premotor and primary motor
      cortices might elicit net facilitatory cortico-reticular effects that could
      interact at the level of the brainstem with a habituated startle to give a
      reticulospinal discharge and electromyographic (EMG) response with a longer
      latency than the direct corticospinal response. Conversely, any reticulo-cortical
      activity evoked by a habituated startle should influence the size of the direct
      response to cortical TMS. EMG was recorded from active left deltoid muscle in
      nine healthy volunteers. Acoustic stimulation was delivered binaurally through
      headphones and repeated until the startle response was habituated. When TMS was
      centred over the right dorsal premotor or primary motor cortices and delivered 50
      ms after the habituated acoustic stimulus, the contralateral direct motor evoked
      potential was inhibited, compared with the response elicited by TMS alone. The
      contralateral silent period was shortened and associated with less of a decrease
      in EMG levels relative to TMS alone. Indeed, an actual increase in EMG over
      baseline levels occurred in the later half of the silent period in all subjects.
      We conclude that both cortico-reticular and reticular-cortical effects could be
      elicited in deltoid through the combination of acoustic stimulation and TMS at
      short interstimulus intervals. Effects were similar with TMS over premotor and
      primary motor cortex.

PMID- 14968279
TI  - Cortico-cortical coupling patterns during dual task performance.
AB  - We investigated the neural correlates of dual task performance using EEG
      coherence as a measure of the functional coupling between cortical regions. Nine
      healthy participants performed a rhythmical movement with the right hand and an
      isometric contraction with the left hand, either initiated simultaneously or
      successively. EEG data revealed that dual task performance was associated with
      stronger coherence in left hemispheric and mesial areas than the sum of the tasks
      performed separately in the beta (>12-30 Hz), but not alpha (8-12 Hz), band. This
      effect was more pronounced when the two assignments were initiated
      simultaneously, as opposed to successively. The data demonstrate that the pattern
      of cortico-cortical coupling during bimanual actions is not just the sum of that
      associated with its component parts, but is increased according to coordinative
      demands and processing load.

PMID- 14968280
TI  - Sensory and response contributions to visual awareness in extinction.
AB  - Brain-damaged patients may extinguish contralesional stimuli when ipsilesional
      stimuli are presented simultaneously. Most theories of extinction postulate that
      stimuli compete for pathologically limited attentional resources with a bias to
      process ipsilesional over contralesional stimuli. Implicit in this view is the
      idea that responses follow the outcome of an earlier competition between inputs.
      In the current study of two patients, we used signal detection analyses to test
      the hypothesis that response criteria and response modalities also contribute to
      visual awareness. We found that identification was more sensitive than detection
      in uncovering deficits of contralesional awareness. Extinction was worse with
      bilateral stimuli when the ipsilesional stimulus was identical or similar to the
      target than when it was dissimilar. This diminished awareness was more likely to
      reflect a shift towards more conservative responses rather than diminished
      discrimination of contralesional stimuli. By contrast, one patient was better
      able to discriminate contralesional stimuli when using his contralesional limb to
      indicate awareness of targets than when using his ipsilesional limb. These data
      indicate that the nature of stimuli can modulate response criteria and the motor
      response can affect the sensory discriminability. Sensory discrimination and
      response output are not organized in a simple serial manner. Rather, input and
      output parameters interact in complicated ways to produce visual awareness.
      Visual awareness itself appears to be the outcome of two bottlenecks in
      processing, one having to do with sensory processing that may be covert and the
      other having to do with decision making, which by definition is overt. Finally,
      we advocate the use of signal detection analyses in studies of extinction, a
      method that has been surprisingly neglected in this line of research.

PMID- 14968281
TI  - Induction of locomotor-like EMG activity in paraplegic persons by orthotic gait
      training.
AB  - This is, to our knowledge, the first report demonstrating the effects of orthotic
      gait training on the activity of the spinal locomotor neural networks. Three
      subjects with complete spinal cord injury (SCI) performed 1-h training with
      reciprocating gait orthosis 5 days/week for 12 weeks. The results showed that
      after 3 (n=1) or 6 weeks (n=2) of training, EMG activities synchronized with
      locomotor rhythm appeared in the soleus muscle (SOL) in all subjects, although
      very little EMG activity accompanied the orthotic gait at the early training
      stage. Our results suggest that the induced modulation in the SOL EMG waveforms
      might be attributable to changes in the orthotic gait movement pattern, and/or
      changes in the interneuronal activities of the spinal locomotor neural networks,
      as a result of orthotic gait training.

PMID- 14968282
TI  - Figure copying in Williams syndrome and normal subjects.
AB  - We evaluated the copying abilities of ten subjects with Williams syndrome (WS;
      age 6-14 years) and ten normally developing children (age 3-6 years) matched for
      mental age using the matrices component of the Kaufman Brief Intelligence Test
      (mKBIT). Each subject copied six figures, including line drawings of closed and
      open geometrical shapes (alone and in combination), crossed lines, and
      geometrical shapes made of distinct small, filled circles. Qualitatively,
      subjects of both groups made comparable copies, although several subjects with WS
      drew a continuous line when copying figures composed of distinct circles.
      Quantitatively, the goodness of the copies was assessed by three human observers
      who rated on an analog scale the similarity of each copy to its visual template.
      Ratings were converted to a scale from zero (completely different) to 100 (the
      same) for statistical analyses. We found the following. First, the overall
      goodness of copies of the templates was very similar between the WS and control
      groups (WS: mean=46.7, range=0.89-95.4; control: mean=54.5, range=0.89-98.2).
      Second, there were systematic differences in the goodness of copies between the
      two groups, depending on the features of the figures. Specifically, the goodness
      of copies of control subjects was almost the same as that of WS subjects for
      simple line figures, but was consistently better for composite line figures, and
      even better for figures in which the shape was made of small, filled circles.
      Third, there was a significant relation between the goodness of copies (dependent
      variable) and mental age (mKBIT, independent variable) in both groups, although
      it was stronger and more highly statistically significant in the control than the
      WS group. These findings indicate that the principles guiding copying are similar
      in the two groups and suggest that WS is a case of developmental rather than
      deviance disorder.

PMID- 14968283
TI  - Glutamate, but not aspartate, is enriched in trigeminothalamic tract terminals
      and associated with their synaptic vesicles in the rat nucleus submedius.
AB  - To examine the possible roles of glutamate and aspartate as neurotransmitters in
      the nucleus submedius (Sm) of rats, the distributions of these amino acids were
      examined by electron microscopic immunogold labeling. High levels of glutamate
      were detected in trigeminothalamic tract terminals anterogradely labeled with
      horseradish peroxidase conjugates. These terminals also displayed a positive
      correlation between the densities of synaptic vesicles and gold particles
      signaling glutamate. In contrast, aspartate levels in such terminals were low and
      displayed no correlation with the density of synaptic vesicles. Terminals of
      presumed cortical origin contained the highest estimated levels of glutamate, but
      the positive correlation between glutamate signal and synaptic vesicle density
      did not reach statistical significance, presumably due to technical factors. The
      latter terminals also contained relatively high levels of aspartate, though
      without any correlation to synaptic vesicle density. The present findings provide
      strong support for glutamate, but not aspartate, as a trigeminothalamic tract
      neurotransmitter responsible for the fast synaptic transmission of nociceptive
      signals to neurons in the rat nucleus submedius. Aspartate presumably serves
      metabolic roles in these terminals. With respect to terminals of presumed
      cortical origin, our data are not at odds with the notion that also these
      terminals use glutamate as their neurotransmitter. Our findings do not support a
      neurotransmitter role for aspartate in the latter terminals, although such a role
      cannot be entirely refuted.

PMID- 14968284
TI  - Determination of oil and water content in olive pomace using near infrared and
      Raman spectrometry. A comparative study.
AB  - Near infrared (NIR) reflectance and Raman spectrometry were compared for
      determination of the oil and water content of olive pomace, a by-product in olive
      oil production. To enable comparison of the spectral techniques the same sample
      sets were used for calibration (1.74-3.93% oil, 48.3-67.0% water) and for
      validation (1.77-3.74% oil, 50.0-64.5% water). Several partial least squares
      (PLS) regression models were optimized by cross-validation with cancellation
      groups, including different spectral pretreatments for each technique. Best
      models were achieved with first-derivative spectra for both oil and water
      content. Prediction results for an independent validation set were similar for
      both techniques. The values of root mean square error of prediction (RMSEP) were
      0.19 and 0.20-0.21 for oil content and 2.0 and 1.8 for water content, using Raman
      and NIR, respectively. The possibility of improving these results by combining
      the information of both techniques was also tested. The best models constructed
      using the appended spectra resulted in slightly better performance for oil
      content (RMSEP 0.17) but no improvement for water content.

PMID- 14968285
TI  - Voltammetry of lead cations on a new type of silver composite electrode in the
      presence of other cations.
AB  - A new type of silver composite electrode was examined, prepared from silver,
      graphite powder, and methacrylate resin. The effects of the presence of various
      cations (cadmium, copper, bismuth, thallium), anions (chlorides), surface-active
      substances (Triton X-100), and oxygen on the anodic-stripping voltammetric
      determination of lead were studied. It was found that the effect of
      underpotential deposition at the composite electrode differs from that produced
      at a metallic silver electrode, mainly at low concentrations of the deposited
      metal. The use of this type of silver composite electrode in differential pulse
      anodic-stripping voltammetry enables direct determination of lead in natural
      water samples without elimination of surface-active substances (LOD about 3
      microg L(-1)).

PMID- 14968286
TI  - Flow injection analysis of gallic acid with inhibited electrochemiluminescence
      detection.
AB  - A flow injection (FI)-electrochemiluminescent (ECL) method has been developed for
      the determination of gallic acid, based on an inhibition effect on the
      Ru(bpy)(3)(2+)/tri- n-propylamine (TPrA) ECL system in pH 8.0 phosphate buffer
      solution. The method is simple and convenient with a determination limit of
      9.0x10(-9) mol/L and a dynamic concentration range of 2x10(-8)-2x10(-5) mol/L.
      The relative standard deviation (RSD) was 1.0% for 1.0x10(-6) mol/L gallic acid (
      n=11). It was successfully applied to the determination of gallic acid in Chinese
      proprietary medicine-Jianming Yanhou Pian. The inhibition mechanism proposed for
      the quenching effect of the gallic acid on the Ru(bpy)(3)(2+)/TPrA ECL system was
      the interaction of electrogenerated Ru(bpy)(3)(2+*) and o-benzoquinone derivative
      at the electrode surface. The ECL emission spectra and UV-visible absorption
      spectra were applied to confirm the mechanism.

PMID- 14968287
TI  - In-situ FTIR investigations on the reduction of vinylene electrolyte additives
      suitable for use in lithium-ion batteries.
AB  - Lithium-ion batteries operate beyond the thermodynamic stability of the aprotic
      organic electrolyte used and electrolyte decomposition occurs at both electrodes.
      The electrolyte must therefore be composed in a way that its decomposition
      products form a film on the electrodes which stops the decomposition reactions
      but is still permeable to the Li(+) cations which are the charge carriers. At the
      graphite anode, this film is commonly referred to as a solid electrolyte
      interphase (SEI). Aprotic organic compounds containing vinylene groups can form
      an effective SEI on a graphitic anode. As examples, vinyl acetate (VA) and
      acrylonitrile (AN) have been investigated by in-situ Fourier transform infrared
      (FTIR) spectroscopy in a specially developed IR cell. The measurements focus on
      electrolyte decomposition and the mechanism of SEI formation in the presence of
      VA and AN. We conclude that cathodic reduction of the vinylene groups (i.e., via
      reduction of the double bond) in the electrolyte additives is the initiating and
      thus a most important step of the SEI-formation process, even in an electrolyte
      which contains only a few percent (i.e. electrolyte additive amounts) of the
      compound. The possibility of electropolymerization of the vinylene monomers in
      the battery electrolytes used is critically discussed on the basis of the IR data
      obtained.

PMID- 14968288
TI  - Hardness and phase analysis of IN 718 deformed at high strain rate.
AB  - Specimens of the nickel base alloy IN 718 deformed at high strain rate
      (approximately 10 s(-1)), as realized in a screw press, have higher strength than
      parts forged conventionally in a hydraulic press. Microstructure analyses in
      light and transmission electron microscopes reveal the precipitation of very
      small Ni(3)Nb particles (gamma"-phase) to be the reason for the increased
      hardness. Several processing routes are discussed and analyzed in relation to the
      TTT-diagram of IN 718.

PMID- 14968289
TI  - Elemental contents in Napoleon's hair cut before and after his death: did
      Napoleon die of arsenic poisoning?
AB  - Whether or not Napoleon died of arsenic poisoning is an open question on which
      debate has been active since 1960. This work examined several of his hairs, cut
      at different times and in different places: two pieces cut the day after his
      death on the island of St. Helena (1821) and two pieces cut seven years earlier
      (1814) during his first exile on the island of Elba. INAA results show that all
      of the samples of Napoleon's hair have an elevated arsenic concentration. These
      results disfavor the arsenic poisoning theory. Aside from arsenic, 18 other
      elements are reported, providing additional information for examining the arsenic
      poisoning theory.

PMID- 14968291
TI  - Quantitative ultrasound measurements of bone: measurement error, discordance, and
      their effects on longitudinal studies.
AB  - The performance of quantitative ultrasound (QUS) for the assessment of
      osteoporotic fracture must be fully defined if it is to be used in the clinical
      setting. We have examined the precision and reproducibility of two ultrasound
      instruments in 1,267 institutionalized elderly men and women (mean age 82.1 and
      85.9 years, respectively). Measurement of BUA and VOS was reliable, least
      significant change for BUA being 2.4% and for VOS 0.3% using the CUBA McCue
      instrument and 2.7% for BUA using the Metra QUS-2. Importantly, age was not found
      to influence the precision of either parameter. Comparison of the instruments
      showed the QUS-2 measures BUA higher than the CUBA by 1.9 dB/MHz (+/-9.55
      dB/MHz). Moreover classification of individuals as osteoporotic by machine
      derived T-score was different between instruments (kappa = 0.44 in men and kappa
      = 0.62 in women). Fifty-six residents were remeasured by CUBA after 2.2 years;
      BUA was observed to decrease by 5.2% (+/-16.5%, p = 0.02) without significant
      change in VOS, suggesting BUA is more useful in longitudinal studies. In
      conclusion, ultrasound measurements were highly reliable and sensitive to
      longitudinal change even in the very elderly. However, diagnosis by T-score
      criteria was instrument specific, and such criteria should be interpreted with
      caution in the assessment of fracture risk.

PMID- 14968292
TI  - Redox state-dependent and sorbitol accumulation-independent diabetic albuminuria
      in mice with transgene-derived human aldose reductase and sorbitol dehydrogenase
      deficiency.
AB  - AIMS/HYPOTHESIS: We investigated the role played by sorbitol accumulation in the
      kidney in the development of diabetic albuminuria. METHODS: We created mice ( hAR
      Tg:SDH null) with transgene-derived human aldose reductase and sorbitol
      dehydrogenase (SDH) deficiency, and analysed (i). the contribution of accumulated
      sorbitol to urinary albumin excretion rate, and (ii). the effect of the aldose
      reductase inhibitor, epalrestat, on the diabetic redox state, including decreased
      renal reduced glutathione concentrations or increased lactate to pyruvate ratios
      in the diabetic kidney. RESULTS: Compared to littermates, non-diabetic transgenic
      mice had a 2.6-fold increase in aldose reductase mRNA. In a diabetic group,
      aldose reductase mRNA in hAR-Tg mice was 2.7-fold higher than in littermates. In
      the diabetic and non-diabetic groups, hAR-Tg:SDH null mice had the highest
      sorbitol content among all four genetic types including hAR-Tg:SDH null, SDH
      null, hAR-Tg and littermates. The urinary albumin excretion rate in non-diabetic
      groups was similar in the four genetic types of mouse. In diabetic groups it was
      greater than in non-diabetic groups, but did not correlate with the sorbitol
      content among the four genetic types of mouse. When aldose reductase inhibitor
      and streptozotocin were given simultaneously at 6 weeks of age, epalrestat
      prevented diabetic increases in urinary albumin excretion rate and completely
      prevented diabetic decreases in reduced glutathione concentrations and diabetic
      increases in lactate to pyruvate ratios, even in the presence of transgenic
      aldose reductase. CONCLUSIONS/INTERPRETATION: The degree of diabetic albuminuria
      in genetically modified mice is dependent on the redox state and independent of
      polyol accumulation; aldose reductase inhibitor can prevent diabetic albuminuria
      by normalising diabetic redox changes.

PMID- 14968293
TI  - Stable and functional regeneration of pancreatic beta-cell population in nSTZ
      rats treated with tungstate.
AB  - AIMS/HYPOTHESIS: Sodium tungstate has recently emerged as an effective oral
      treatment for diabetes. We examined the effects of tungstate administration in
      the beta-cell mass of the pancreas as well as its therapeutic potential. METHODS:
      Sodium tungstate was administered via drinking water to healthy and neonatal
      streptozotocin (nSTZ)-diabetic rats for one month. The pancreas from each rat was
      removed and morphometric and immunocytochemical studies were carried out. The
      molecular mechanism of tungstate's action was also studied. RESULTS: In nSTZ rats
      administration of this compound normalised glycaemia, and increased insulinaemia
      and islet insulin content. Blood glucose concentrations were normalised as early
      as on day 4 of treatment, and tungstate treatment produced a partial recovery of
      beta-cell mass. The rats remained normoglycaemic after tungstate withdrawal.
      Morphometric studies showed that the increase in beta-cell mass was not due to
      beta-cell hypertrophy but to hyperplasia, with an increase in islet density in
      treated diabetic rats. Tungstate treatment increased extra-islet beta-cell
      replication without modifying intra-islet beta-cell replication rates. Moreover,
      the treatment induced increases in insulin-positive cells located close to ducts;
      and in PDX-1 positive cells scattered in the exocrine tissue, suggesting active
      neogenesis. In islets from treated diabetic rats, tungstate is able to increase
      the phosphorylation state of PDX-1 through the activation of p38.
      CONCLUSION/INTERPRETATION: These observations indicate that tungstate treatment
      is able to regenerate a stable, functional pancreatic beta-cell population which
      leads to and maintains normoglycaemia.

PMID- 14968294
TI  - The EGIR-RISC STUDY (The European group for the study of insulin resistance:
      relationship between insulin sensitivity and cardiovascular disease risk): I.
      Methodology and objectives.
AB  - AIMS/HYPOTHESES: Insulin resistance is thought to be a key predictor for the
      development of Type 2 diabetes mellitus and cardiovascular disease (CVD), a
      leading cause of morbidity and premature mortality in Europe. Insulin resistance
      is influenced by both genetic and lifestyle factors (e.g. obesity and physical
      inactivity). The RISC (Relationship between Insulin Sensitivity and
      Cardiovascular disease) Study is using the infrastructure of an extended European
      collaborative research group to study insulin resistance and CVD risk in 1500
      healthy people aged 30 to 60 years from 20 centres in 13 countries. METHODS:
      Baseline measurements of glucose tolerance and insulin sensitivity are made by
      the oral glucose tolerance test and the euglycaemic insulin clamp, respectively;
      carotid artery intima-medial thickness (by ultrasound), ankle/brachial pressure
      index and electrocardiography will enable evaluation of subclinical CVD at
      baseline and at follow-up. Classic CVD risk factors, as well as socioeconomic and
      lifestyle factors will be recorded at baseline; samples for measurement of
      biochemical and genetic markers will be collected and stored for future analyses.
      Investigations will be repeated after 3 and 10 years to evaluate the relationship
      between insulin resistance and the development of atherosclerosis as measured by
      carotid artery intima-media thickness. Development of Type 2 diabetes,
      dyslipidaemia, obesity, hypertension and cardiovascular events are additional
      endpoints. CONCLUSIONS: This study will evaluate the importance of insulin
      resistance in the development of CVD and diabetes, and has implications for the
      development of prevention and treatment strategies.

PMID- 14968296
TI  - Incretins, insulin secretion and Type 2 diabetes mellitus.
AB  - When glucose is taken orally, insulin secretion is stimulated much more than it
      is when glucose is infused intravenously so as to result in similar glucose
      concentrations. This effect, which is called the incretin effect and is estimated
      to be responsible for 50 to 70% of the insulin response to glucose, is caused
      mainly by the two intestinal insulin-stimulating hormones, glucagon-like peptide
      1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Their
      contributions have been confirmed in mimicry experiments, in experiments with
      antagonists of their actions, and in experiments where the genes encoding their
      receptors have been deleted. In patients with Type 2 diabetes, the incretin
      effect is either greatly impaired or absent, and it is assumed that this could
      contribute to the inability of these patients to adjust their insulin secretion
      to their needs. In studies of the mechanism of the impaired incretin effect in
      Type 2 diabetic patients, it has been found that the secretion of GIP is
      generally normal, whereas the secretion of GLP-1 is reduced, presumably as a
      consequence of the diabetic state. It might be of even greater importance that
      the effect of GLP-1 is preserved whereas the effect of GIP is severely impaired.
      The impaired GIP effect seems to have a genetic background, but could be
      aggravated by the diabetic state. The preserved effect of GLP-1 has inspired
      attempts to treat Type 2 diabetes with GLP-1 or analogues thereof, and
      intravenous GLP-1 administration has been shown to be able to near-normalize both
      fasting and postprandial glycaemic concentrations in the patients, perhaps
      because the treatment compensates for both the impaired secretion of GLP-1 and
      the impaired action of GIP. Several GLP-1 analogues are currently in clinical
      development and the reported results are, so far, encouraging.

PMID- 14968297
TI  - Adipocytes release a soluble form of VAP-1/SSAO by a metalloprotease-dependent
      process and in a regulated manner.
AB  - AIMS/HYPOTHESIS: Vascular adhesion protein-1 (VAP-1), which is identical to
      semicarbazide-sensitive amine oxidase (SSAO), is a dual-function membrane protein
      with adhesion properties and amine oxidase activity. A soluble form of VAP-1 is
      found in serum, where concentrations are enhanced in diabetes and obesity. In
      vitro, soluble VAP-1 enhances lymphocyte adhesion to endothelial cells, thus
      possibly participating in the enhanced lymphocyte adhesion capacity that is
      implicated in the cardiovascular complications associated with diabetes or
      obesity. In both, the tissue origin of the soluble VAP-1/SSAO is unknown. We
      examined whether adipose tissue, which has abundant expression of VAP-1/SSAO, is
      a source of soluble VAP-1. METHODS: We detected VAP-1/SSAO in plasma of diabetic
      animals, with or without VAP-1 immunoprecipitation, and in culture medium from
      3T3-L1 adipocytes and human adipose tissue explants. VAP-1 protein glycosylation
      was measured. RESULTS: Diabetic and obese animals have increased plasma SSAO
      activity associated with VAP-1 protein. We also found that 3T3-L1 adipocytes and
      human adipose tissue explants release a soluble form of VAP-1/SSAO, which derives
      from the membrane. The release of soluble VAP-1 was enhanced by exposure of
      murine and human adipocytes to TNF-alpha and blocked by batimastat, a
      metalloprotease inhibitor. Partial ablation of adipose tissue reduced plasma SSAO
      activity in normal and diabetic rats. CONCLUSIONS/INTERPRETATION: Adipose cells
      are a source of soluble VAP-1/SSAO released by shedding of the membrane form. The
      release of SSAO is regulated by TNF-alpha and insulin. By releasing VAP-1/SSAO,
      adipose cells could contribute to the atherogenesis and vascular dysfunction
      associated with diabetes and obesity.

PMID- 14968298
TI  - Non-esterified fatty acids are deleterious for human pancreatic islet function at
      physiological glucose concentration.
AB  - AIMS/HYPOTHESIS: Whether excess glucose (glucotoxicity) and excess non-esterified
      fatty acids (lipotoxicity) act synergistically or separately to alter beta-cell
      function on Type 2 diabetes remains controversial. We examined the influence of
      non-esterified fatty acids, with or without concomitant increased glucose
      concentrations, on human islet function and on the expression of genes involved
      in lipid metabolism. METHODS: Human islets isolated from non-diabetic and non
      obese donors were cultured with 5.5, 16 or 30 mmol/l glucose, and when
      appropriate with 1 or 2 mmol/l non-esterified fatty acids. After 48 h, glucose
      stimulated insulin secretion, insulin content, triglyceride content and
      expression of different genes were evaluated. RESULTS: Non-esterified fatty acids
      decreased glucose-stimulated insulin secretion, insulin content and increased
      triglyceride content of human isolated islets, independently from the deleterious
      effect of glucose. Increased glucose concentrations also decreased glucose
      stimulated insulin secretion and insulin content, but had no influence on
      triglyceride content. Glucose-stimulated insulin secretion of islets appeared to
      be significantly correlated with their triglyceride content. Glucose and non
      esterified fatty acids modified the gene expression of carnitine
      palmitoyltransferase-I, acetyl-CoA carboxylase, acyl-CoA oxidase and uncoupling
      protein 2. CONCLUSION/INTERPRETATION: In our model of isolated human islets,
      increased glucose and non-esterified fatty acids separately reproduced the two
      major beta-cell alterations observed in vivo, i.e. loss of glucose-stimulated
      insulin secretion and reduction in islet insulin content. Our results also
      suggest that this deleterious effect was, at least in part, mediated by
      modifications in lipid metabolism gene expression.

PMID- 14968299
TI  - Insulin expressing cells from differentiated embryonic stem cells are not beta
      cells.
AB  - AIM/HYPOTHESIS: Embryonic stem (ES) cells have been proposed as a potential
      source of tissue for transplantation for the treatment of Type 1 diabetes.
      However, studies showing differentiation of beta cells from ES cells are
      controversial. The aim of this study was to characterise the insulin-expressing
      cells differentiated in vitro from ES cells and to assess their suitability for
      the treatment of diabetes. METHODS: ES cell-derived insulin-expressing cells were
      characterised by means of immunocytochemistry, RT-PCR and functional analyses.
      Activation of the Insulin I promoter during ES-cell differentiation was assessed
      in ES-cell lines transfected with a reporter gene. ES cell-derived cultures were
      transplanted into STZ-treated SCID-beige mice and blood glucose concentrations of
      diabetic mice were monitored for 3 weeks. RESULTS: Insulin-stained cells
      differentiated from ES cells were devoid of typical beta-cell granules, rarely
      showed immunoreactivity for C-peptide and were mostly apoptotic. The main
      producers of proinsulin/insulin in these cultures were neurons and neuronal
      precursors and a reporter gene under the control of the insulin I promoter was
      activated in cells with a neuronal phenotype. Insulin was released into the
      incubation medium but the secretion was not glucose-dependent. When the cultures
      were transplanted in diabetic mice they formed teratomas and did not reverse the
      hyperglycaemic state. CONCLUSIONS/INTERPRETATION: Our studies show that insulin
      positive cells in vitro-differentiated from ES cells are not beta cells and
      suggest that alternative protocols, based on enrichment of ES cell-derived
      cultures with cells of the endodermal lineage, should be developed to generate
      true beta cells for the treatment of diabetes.

PMID- 14968300
TI  - Mapping of quantitative trait loci for partial resistance to Mycosphaerella
      pinodes in pea (Pisum sativum L.), at the seedling and adult plant stages.
AB  - The inheritance of resistance to Ascochyta blight, an economically important
      foliar disease of field pea ( Pisum sativum L.) worldwide, was investigated.
      Breeding resistant pea varieties to this disease, caused by Mycosphaerella
      pinodes, is difficult due to the availability of only partial resistance. We
      mapped and characterized quantitative trait loci (QTLs) for resistance to M.
      pinodes in pea. A population of 135 recombinant inbred lines (RILs), derived from
      the cross between DP (partially resistant) and JI296 (susceptible), was genotyped
      with morphological, RAPD, SSR and STS markers. A genetic map was elaborated,
      comprising 206 markers distributed over eight linkage groups and covering 1,061
      cM. The RILs were assessed under growth chamber and field conditions at the
      seedling and adult plant stages, respectively. Six QTLs were detected at the
      seedling stage, which together explained up to 74% of the variance. Ten QTLs were
      identified at the adult plant stage in the field, and together these explained
      56.6-67.1% of the variance, depending on the resistance criteria and the organ
      considered. Four QTLs were detected under both growth chamber and field
      conditions, suggesting they were not plant-stage dependent. Three QTLs for
      flowering date and three QTLs for plant height were also identified in the RIL
      population, some of which co-located with QTLs for resistance. The relationship
      between QTLs for resistance to M. pinodes, plant height and flowering date is
      discussed.

PMID- 14968301
TI  - One hundred and one new microsatellite loci derived from ESTs (EST-SSRs) in bread
      wheat.
AB  - Four hundred and seventy-eight microsatellite markers derived from expressed
      sequence tags (EST-SSRs) were screened among three mapping populations (W
      7984xOpata 85, WOpop; LumaixHanxuan, LHpop; WenmaixShanhongmai, WSpop). The
      number of polymorphic EST-SSR primer pairs found in WOpop, LHpop and WSpop was
      92, 58 and 29 respectively. A total of 101 EST-SSR loci amplified from 88 primer
      sets were distributed over the 20 chromosomes of the reference maps (no markers
      were located on chromosome 4B). These 101 mapped EST-SSR markers add to the
      existing 450 microsatellite loci previously mapped in bread wheat. Seventy-four
      of the 101 loci showed significant similarities to known genes, including 24
      genes involved in metabolism, 4 in cellular structures, 9 in stress resistance,
      12 in transcription, 2 in development, 2 transporters and 21 storage proteins.
      Besides gliadin and glutenin, most of the 53 genes with putative functions were
      mapped for the first time by EST-SSR markers in bread wheat. Sequence alignment
      of the mapped wheat EST-SSR loci allowed tentative assignment of functionality to
      the other members of grasses family. Colinearity combined with homology
      information offers an attractive approach to comparative genomics.

PMID- 14968302
TI  - Inheritance of the Md-ACS1 gene and its relationship to fruit softening in apple
      ( Malus x domestica Borkh.).
AB  - The 1-aminocyclopropane-1-carboxylic acid synthase (ACS) gene is a member of the
      ACS gene family that is involved in apple ( Malus x domestica Borkh.) fruit
      ripening. Presence of an allele ( Md-ACS1-2) of this gene is associated with low
      internal ethylene concentration in some apple cultivars. In this study,
      inheritance of Md-ACS1 was determined for 50 apple cultivars/advanced selections
      and 101 F(1) seedlings from five populations. Following this, the softening
      pattern of apples stored at 20 degrees C for up to 40 days was examined using 35
      fruiting cultivars/selections of defined Md-ACS1 status. Md-ACS1 is inherited in
      a Mendelian fashion and was found to be linked to fruit softening. Maturity
      season of genotypes also significantly affected fruit softening. Late-season
      genotypes in the Md- ACS1-2/2 class had the slowest rate of softening, while
      early-season Md- ACS1-1/1 genotypes had the most rapid softening rate. The
      implications of these results are discussed in relation to parental selection and
      breeding for storage ability in apple.

PMID- 14968303
TI  - Amplified fragment length polymorphism for genetic diversity assessment in globe
      artichoke.
AB  - Globe artichoke ( Cynara cardunculus L. var. scolymus L.) is a diploid (2 n=2
      x=34), predominantly cross-pollinated plant native to the Mediterranean basin,
      and Italy contains the richest primary cultivated 'gene pool'. Commercial
      production is mainly based on perennial cultivation of vegetatively propagated
      clones that are highly heterozygous and segregate widely when progeny-tested.
      Analysis of the artichoke genome by means of molecular markers has been limited
      to a few studies; here we report on the genetic relatedness among 118 artichoke
      accessions, including clones belonging to the same varietal type, two accessions
      of cultivated cardoon ( C. cardunculus L. var. altilis DC.) and four accessions
      of wild cardoon [ C. cardunculus L. var. sylvestris (Lamk) Fiori] as measured by
      amplified fragment length polymorphism (AFLP). Eight primer combinations yielded
      a total of 667 bands, of which 519 were polymorphic. Genetic similarities among
      accessions were calculated according to Jaccard's Similarity Index and used to
      construct a dendrogram based on the unweighted pair group method using arithmetic
      averages. Our results demonstrate that AFLP markers can be useful in evaluating
      Cynara cardunculus genetic diversity and in classifying accessions to
      phylogenetic groups based on their genetic similarity values. Genetic variation
      among artichoke clones belonging to the same varietal type was in some cases
      higher than that found among accessions differently named and coming from
      different areas. The lowest Jaccard's Similarity Index found within a varietal
      type can be considered as a threshold for the identification of accessions which
      share an analogous genetic background. This will enable the selection of
      representatives in order to develop and manage a germplasm 'core collection' as
      well as the identification of suitable material for future artichoke breeding
      efforts.

PMID- 14968304
TI  - Duplicate marker loci can result in incorrect locus orders on linkage maps.
AB  - Genetic linkage maps, constructed from multi-locus recombination data, are the
      basis for many applications of molecular markers. For the successful employment
      of a linkage map, it is essential that the linear order of loci on a chromosome
      is correct. The objectives of this theoretical study were to (1) investigate the
      occurrence of incorrect locus orders caused by duplicate marker loci, (2) develop
      a statistical test for the detection of duplicate markers, and (3) discuss the
      implications for practical applications of linkage maps. We derived conditions,
      under which incorrect locus orders do or do not occur with duplicate marker loci
      for the general case of n markers on a chromosome in a BC(1) mapping population.
      We further illustrated these conditions numerically for the special case of four
      markers. On the basis of the extent of segregation distortion, an exact test for
      the presence of duplicate marker loci was suggested and its power was
      investigated numerically. Incorrect locus orders caused by duplicate marker loci
      can (1) negatively affect the assignment of target genes to chromosome regions in
      a map-based cloning experiment, (2) hinder indirect selection for a favorable
      allele at a quantitative trait locus, and (3) decrease the efficiency of reducing
      the length of the chromosome segment attached to a target gene in marker-assisted
      backcrossing.

PMID- 14968305
TI  - The tomato homolog of the gene encoding UV-damaged DNA binding protein 1 (DDB1)
      underlined as the gene that causes the high pigment-1 mutant phenotype.
AB  - A tomato EST sequence, highly homologous to the human and Arabidopsis thaliana UV
      damaged DNA binding protein 1 (DDB1), was mapped to the centromeric region of the
      tomato chromosome 2. This region was previously shown to harbor the HP-1 gene,
      encoding the high pigment-1 ( hp-1) and the high pigment-1(w) ( hp-1(w)) mutant
      phenotypes. Recent results also show that the A. thaliana DDB1 protein interacts
      both genetically and biochemically with the protein encoded by DEETIOLATED1, a
      gene carrying three tomato mutations that are in many respects isophenotypic to
      hp-1: high pigment-2 ( hp-2), high pigment-2(j) ( hp-2(j)) and dark green ( dg).
      The entire coding region of the DDB1 gene was sequenced in an hp-1 mutant and its
      near-isogenic normal plant in the cv. Ailsa Craig background, and also in an hp
      1(w) mutant and its isogenic normal plant in the GT breeding line background.
      Sequence analysis revealed a single A(931)-to-T(931) base transversion in the
      coding sequence of the DDB1 gene in the hp-1 mutant plants. This transversion
      results in the substitution of the conserved asparagine at position 311 to a
      tyrosine residue. In the hp-1(w) mutant, on the other hand, a single G(2392)-to
      A(2392) transition was observed, resulting in the substitution of the conserved
      glutamic acid at position 798 to a lysine residue. The single nucleotide
      polymorphism that differentiates hp-1 mutant and normal plants in the cv. Ailsa
      Craig background was used to design a pyrosequencing genotyping system. Analysis
      of a resource F(2) population segregating for the hp-1 mutation revealed a very
      strong linkage association between the DDB1 locus and the photomorphogenic
      response of the seedlings, measured as hypocotyl length (25<LOD score<26,
      R(2)=62.8%). These results strongly support the hypothesis that DDB1 is the gene
      encoding the hp-1 and hp-1(w) mutant phenotypes.

PMID- 14968306
TI  - Comparative AB-QTL analysis in barley using a single exotic donor of Hordeum
      vulgare ssp. spontaneum.
AB  - This paper reports on the first comparative advanced backcross quantitative trait
      locus (AB-QTL) study in barley. The BC(2)F(2) population Hx101 was generated from
      crossing var. Harry [H; Hordeum vulgare ssp. vulgare ( Hv)] with ISR101-23 [101;
      H. v. ssp. spontaneum ( Hsp)]. The results of the AB-QTL analysis for 13
      quantitative traits are presented and, subsequently, compared with the AB-QTL
      study of the barley cross Apex x ISR101-23 (Ax101; Pillen et al., Theor Appl
      Genet 107:340-352). Both AB populations share the exotic Hsp donor accession
      ISR101-23. In Hx101, 108 putative QTLs (17%) were identified among the 650
      markerxtrait combinations tested. Altogether 52 (48 %) favorable effects were
      identified from the exotic parent. At these marker loci, the homozygous Hsp
      genotype was associated with an improvement in the trait compared to the
      homozygous Hv genotype. The percentage of QTLs detected in Hx101 was comparable
      to that in Ax101 (17% vs. 15%), however more favorable exotic QTL alleles were
      located in Hx101 than in Ax101 (48% vs. 34%). In Hx101, the Hsp QTL allele at
      EBmac0679([4H]) was associated with a yield increase of 5.9% averaged across the
      six environments tested. A comparison of putative QTLs between Hx101 and Ax101
      was based on 26 shared SSR markers. In total, 26% of the putative QTLs could be
      detected simultaneously in both AB populations. This finding indicates that only
      a portion of the QTL effects of the donor allele can be transferred from one
      elite recipient to the next.

PMID- 14968307
TI  - High-oleate peanut mutants result from a MITE insertion into the FAD2 gene.
AB  - A high-oleate trait in the cultivated peanut ( Arachis hypogaea L.) was reported
      to rely on the allelic composition of the two homeologous, microsomal oleoyl-PC
      desaturase genes ( ahFAD2A or ahFAD2B). The enzyme activity of either ahFAD2A or
      ahFAD2B is sufficient for a normal oleate phenotype, and a significant reduction
      in the levels of ahFAD2B and a mutation in ahFAD2A were reported to be
      responsible for the high-oleate phenotype in one chemically induced mutant (M2
      225) and one derived from a naturally occurring (8-2122) mutant. Here, we report
      an insertion of the same miniature inverted-repeat transposable element (MITE) in
      the ahFAD2B gene in another chemically induced mutant (Mycogen-Flavo) and the
      previously characterized M2-225 mutant. In both cases, this MITE insertion in
      ahFAD2B causes a frameshift, resulting in a putatively truncated protein sequence
      in both mutants. The insertion of this MITE in ahFAD2B, in addition to the point
      mutation in ahFAD2A, appears to be the cause of the high-oleate phenotype in
      Mycogen-Flavo and M2-225 mutants. Utilizing sequences of the MITE, we developed a
      DNA marker strategy to differentiate the two insertion-containing mutants from
      the normal oleate peanut variety (AT-108) and the naturally occurring, high
      oleate mutant 8-2122. Reverse transcript-PCR/differential digestion results
      reveal the expression of both ahFAD2A and ahFAD2B genes in Mycogen-Flavo mutant.
      This result is in contrast to the observation that ahFAD2B transcripts are
      greatly reduced in the M2-225 mutant having the MITE insertion further 3' in
      ahFAD2B gene.

PMID- 14968308
TI  - Positional cloning of the rice Rf-1 gene, a restorer of BT-type cytoplasmic male
      sterility that encodes a mitochondria-targeting PPR protein.
AB  - The combination of cytoplasmic male sterility (CMS) in one parent and a restorer
      gene ( Rf) to restore fertility in another are indispensable for the development
      of hybrid varieties. We have found a rice Rf-1 gene that restores BT-type CMS by
      applying a positional cloning strategy. Using linkage analysis in combination
      with 6,104 BC(1)F(3) progeny derived from a cross between two near-isogenic lines
      (NILs) differing only at the Rf-1 locus, we delimited the Rf-1 gene to a 22.4-kb
      region in the rice genome. Duplicate open reading frames ( Rf-1A and Rf-1B) with
      a pentatricopeptide (PPR) motif were found in this region. Since several
      insertions and/or deletions were found in the regions corresponding to both the
      Rf-1A and Rf-1B genes in the maintainer's allele, they may have lost their
      function. Rf-1A protein had a mitochondria-targeting signal, whereas Rf-1B did
      not. The Rf-1B gene encoded a shorter polypeptide that was determined by a
      premature stop codon. Based on the function of the Rf-1 gene, its product is
      expected to target mitochondria and may process the transcript from an atp6/orf79
      region in the mitochondrial genome. Since the Rf-1A gene encodes a 791-amino acid
      protein with a signal targeting mitochondria and has 16 repeats of the PPR motif,
      we concluded that Rf-1A is the Rf-1 gene. Nine duplications of Rf-1A homologs
      were found around the Rf-1 locus in the Nipponbare genome. However, while some of
      them encoded proteins with the PPR motif, they do not restore BT-type CMS based
      on the lack of co-segregation with the restoration phenotype. These duplicates
      may have played diversified roles in RNA processing and/or recombination in
      mitochondria during the co-evolution of these genes and the mitochondrial genome.

PMID- 14968309
TI  - Quantitative trait loci for broomrape (Orobanche cumana Wallr.) resistance in
      sunflower.
AB  - Broomrape (Orobanche cumana Wallr.) is a root parasite of sunflower that is
      regarded as one of the most important constraints of sunflower production in the
      Mediterranean region. Breeding for resistance is the most effective method of
      control. P-96 is a sunflower line which shows dominant resistance to broomrape
      race E and recessive resistance to the very new race F. The objective of this
      study was to map and characterize quantitative trait loci (QTL) for resistance to
      race E and to race F of broomrape in P-96. A population from a cross between P-96
      and the susceptible line P-21 was phenotyped for broomrape resistance in four
      experiments, two for race E and two for race F, by measuring different resistance
      parameters (resistance or susceptibility, number of broomrape per plant, and
      proportion of resistant plants per F(3) family). This population was also
      genotyped with microsatellite and RFLP markers. A linkage map comprising 103
      marker loci distributed on 17 linkage groups was developed, and composite
      interval mapping analyses were performed. In total, five QTL ( or1.1, or3.1,
      or7.1 or13.1 and or13.2) for resistance to race E and six QTL ( or1.1, or4.1,
      or5.1, or13.1, or13.2 and or16.1) for resistance to race F of broomrape were
      detected on 7 of the 17 linkage groups. Phenotypic variance for race E resistance
      was mainly explained by the major QTL or3.1 associated to the resistance or
      susceptibility character ( R(2)=59%), while race F resistance was explained by
      QTL with a small to moderate effect ( R(2) from 15.0% to 38.7%), mainly
      associated with the number of broomrape per plant. Or3.1 was race E-specific,
      while or1.1, or13.1 and or13.2 of were non-race specific. Or13.1, and or13.2 were
      stable across the four experiments. Or3.1, and or7.1 were stable over the two
      race E experiments and or1.1 and or5.1 over the two race F experiments. The
      results from this study suggest that resistance to broomrape in sunflower is
      controlled by a combination of qualitative, race-specific resistance affecting
      the presence or absence of broomrape and a quantitative non-race specific
      resistance affecting their number.

PMID- 14968310
TI  - [Vocal cord dysfunction--a "solely pneumatologic" illness?].

PMID- 14968311
TI  - [The ring-pin system in reconstructive head and neck surgery].

PMID- 14968312
TI  - [Olfactory dysfunctions. Epidemiology and therapy in Germany, Austria and
      Switzerland].
AB  - INTRODUCTION: Olfactory dysfunction has been reported to affect more than 200,000
      patients a year in the USA. The aim of this survey was to obtain comparable
      epidemiological data and treatment information on olfactory dysfunction in German
      speaking countries. METHODS: Questionnaires were sent to all otorhinolaryngology
      departments in Germany, Austria and Switzerland; 52% of hospitals completed the
      survey. RESULTS: An average of 46 patients with olfactory dysfunction were
      treated per hospital every month. Hyp- and anosmia were most commonly caused by
      inflammatory diseases of the nose/paranasal sinuses (53%), respiratory
      dysfunction (19%), or postviral conditions (11%). Steroids were used most
      frequently for pharmacological treatment (topically 82%; orally 65%).
      Approximately one third of the clinics used B vitamins, or zinc; 80% of the
      hospitals performed surgery to treat underlying diseases. Acupuncture and smell
      training was used by approximately 20%. CONCLUSION: A total of 79,000 patients
      per year are treated for olfactory dysfunction in German hospitals. The vast
      majority of these disorders (72%) is caused by sinunasal diseases. The quality
      control of therapeutic strategies is urgently needed.

PMID- 14968313
TI  - [The ring-pin anastomosis technique. Long-term clinical experiences with the
      mechanical ring-pin system for microvascular anastomoses in reconstructive head
      and neck surgery ].
AB  - BACKGROUND: Microvascular anastomosis remains one of the most critical aspects of
      free tissue transfer. Since microsurgical suture techniques are complicated and
      time-consuming, other techniques of anastomosis have been created. One of these
      is the ring-pin system. METHODS: Between January 1996 and October 2001, 48
      patients underwent reconstruction with a free radial forearm flap. In 20 patients
      the venous anastomosis was carried out using a ring-pin system with end-to-end
      technique. The clinical results were compared to the other 28 patients in whom
      the anastomosis was sutured with 9-0 prolene. RESULTS: In the group using ring
      pin anastomosis ( n=20), two flaps showed venous congestion within 24 h
      postoperatively. After revision the flaps were well perfused. In the other group
      with sutured vessels ( n=28), a transplant became ischemic in one patient due to
      venous thrombosis and had to be partly removed. The time of anastomosis was
      considerably shortened by the use of the ring-pin system. CONCLUSIONS: The venous
      end-to-end-anastomosis using the ring-pin system can be carried out relatively
      easily and rapidly after a comparatively short period of training. Long-term
      results have shown good tissue tolerance of the material and sufficient blood
      circulation of the grafts.

PMID- 14968314
TI  - [Psychological stress and impaired quality of life in patients with tinnitus].
AB  - OBJECTIVES: The majority of patients with chronic decompensated forms of tinnitus
      have comorbid psychological disorders, possibly accompanied by restricted quality
      of life and participation in everyday activities. There is no standardized tool
      to measure these clinically relevant dimensions. SAMPLE AND METHOD: Both the
      Hospital Anxiety and Depression Scale (HADS) and the Short Form 36 (SF-36) were
      administered to a consecutive sample of patients ( n=110) who were recruited from
      the tinnitus outpatient service in the department of psychiatry and
      psychotherapy. Using the Tinnitus Questionnaire (TF), associations of the HADS
      and SF-36 scales with tinnitus grading were determined and the classification of
      patients (mild-medium-severe-very severe) was evaluated. RESULTS: A severe
      tinnitus grading is correlated to a high extent of anxiety and depression and a
      low quality of life. With the exception of the SF-36 subscale on physical
      functioning, all scales discriminated between the extreme groups (mild vs
      severe/very severe), but less between the two medium groups. CONCLUSIONS:
      Patients with severe decompensated tinnitus (grades III and IV) should be seen
      for diagnosis of psychiatric comorbidity and supportive
      psychotherapy/psychopharmacotherapy used when necessary.

PMID- 14968315
TI  - [Phenotypic characterization of a DFNA6 family with low-frequency hearing loss].
AB  - BACKGROUND: Hereditary hearing impairment is a heterogeneous sensory defect with
      approximately two-thirds of all cases being nonsyndromic. Only two loci (DFNA1
      and DFNA6/14/38) are associated with low frequency sensorineural nonsyndromic
      hearing impairment. DFNA6 was mapped to chromosome 4p16. Recessive mutations in
      the WFS1 gene are responsible for Wolfram syndrome; missense mutations inherited
      as an autosomal dominant result in low frequency sensorineural hearing impairment
      (LFSNHI). PATIENTS AND METHODS: In this study we analyzed the phenotype of a
      large Hungarian family with LFSNHI and linkage to DFNA6. The family contains 14
      affected persons. RESULTS AND CONCLUSION: In general, these patients show a
      postlingual, sensorineural, bilateral, symmetric, nonsyndromic low frequency
      hearing impairment with a slow progression. This impairment is accompanied by
      normal vision and normal vestibular responses.

PMID- 14968316
TI  - [Emergency free microvascular flap transfer for repair of a pharyngeal defect
      manifesting as carotid artery erosion hemorrhage].
AB  - We report on a case of an emergency free flap cover of a pharyngeal defect which
      was made necessary by aggressive digestive salivatory and radiation effects 3
      weeks after neck-dissection and laser ablation of an epidermoid left tonsil
      carcinoma. Life threatening intraoral bleeding resulted from the erosion of
      branches of the external carotid artery. After management of the bleeding,
      massive blood transfusions and restoration of the patient's general condition, a
      sandwich patch cover of the transmural pharyngeal defect was achieved using a
      microvascular lateral arm flap. This aimed at preventing further digestive
      effects and bacterial colonisation of the neurovascular structures at the carotid
      triangle. Unfortunately, due to external mechanical forces, the flap became
      avascular and thus necrotic at the eighth postoperative day; however, until the
      successful replacement by a myocutaneous latissimus dorsi flap it remained water
      tight and fulfilled its sealing task.

PMID- 14968317
TI  - [Benign fibro-osseous tumors of the frontal skull base with intracranial
      extension. Report of 2 cases].
AB  - We report on two patients with ossifying fibroma of the anterior skull base with
      intracranial extension. A psammomatoid ossifying fibroma was removed from a 29
      year old female patient, and in a 37 year old female patient a cemento ossifying
      fibroma was removed. The main clinical symptom in both cases was headache.
      Surgery took place after diagnosis and therapy in an interdisciplinary operation
      with ENT colleagues. The ossifying fibroma is a benign neoplasm mainly affecting
      the maxilla and mandible. Complete removal is better than a curettage of the
      tumor.

PMID- 14968318
TI  - [Alveolar soft tissue sarcoma].
AB  - Alveolar soft part sarcoma is a malignant soft part tumor the etiology of which
      has not yet been clarified. Histopathological examinations show an alveolar or
      pseudoglandular pattern. PAS-positive, diastase resistant intraplasmic inclusion
      bodies are characteristic for this tumor which occurs in the head and neck
      region; mainly the tongue and the orbita. Primary therapy includes total
      resection which can later be combined with radiotherapy or chemotherapy. The
      present study involves a 17 year old patient. We totally removed the tumor and
      then used radiotherapy. The postoperative examinations over 3 years showed
      neither local recurrence nor distant metastases.

PMID- 14968319
TI  - [Child language development delay in craniofacial dysplasia].

PMID- 14968320
TI  - [Inpatient treatment of tonsillectomy from the patient's point of view].
AB  - BACKGROUND: Hospitalization after tonsillectomy for more than 24 h is still
      controversial. In order to obtain the patient's point of view, we designed a
      questionnaire for all patients undergoing tonsillectomy. METHODS AND RESULTS:
      From January 2002, we asked all patients admitted for elective tonsillectomy to
      fill out an anonymous questionnaire on their preferences for the duration of
      hospitalization after surgery. The majority of patients (79.6%) returning the
      questionnaire supported a hospital stay of at least 4 days after surgery. Options
      for a shorter stay of only 24 h or tonsillectomy in day-surgery without overnight
      stay were declined by all patients. CONCLUSION: We found that most patients
      preferred to remain in hospital for about 4 days postoperatively because they
      felt that they would have better access to effective analgesia. Another reason
      involved the increased risk for haemorrhage during the first few days after
      tonsillectomy.

PMID- 14968321
TI  - [Audiologic diagnosis in children. Applicability of different speech material].
AB  - The aim of our study was to establish bench-mark values for speech
      intelligibility in noise for children. We also considered which of the two
      dichotic discrimination tests, Feldmann's or Uttenweiler's, would be most
      suitable for use within this age group. We examined 102 children aged between 7
      and 10 years (second year, primary school), with an average age of 8 years. After
      confirming normal hearing acuity (examination of the ear, tympanometry and
      audiogram), speech perception was tested. This was performed with and without
      noise using the Gottingen Audiometric Speech Test for Children II and the
      monosyllables of the Freiburger Speech Intelligibility Test. The percentage of
      word intelligibility was recorded. Furthermore, dichotic hearing was tested using
      a combination of Feldmann and Uttenweiler dichotic discrimination tests. We rated
      the percentage of correct word pair repetitions with the correct article. The
      results showed that the best method for testing speech perception in noise for
      this age group was the Gottingen Test II for Children. Speech perception below
      70% for word intelligibility should be considered as pathologic. For testing
      dichotic hearing, Uttenweiler's dichotic discrimination test for children was
      most suitable. In this test values below 80% should be considered as pathologic.

PMID- 14968322
TI  - [News in medical law. May 2003 to October 2003].

PMID- 14968323
TI  - [Standard and recently developed methods for the differentiation of
      dermatophytes].
AB  - Although dermatophytoses can often be diagnosed clinically, the identification of
      the dermatophyte species causing the disease gives additional relevant
      information. Species identification is necessary to survey the current
      epidemiologic situation, and it is also needed in each individual case to trace
      back the path of infection, thereby to avoid reinfection, and to optimize the
      therapy. Classical methods to differentiate dermatophytes are based on the
      assessment of their macroscopic and microscopic morphology and on the observation
      of physiologic properties. For scientific taxonomic purposes mating experiments
      are indispensable. In recent years, DNA analysis has been refined to make a
      genetic-based differentiation of dermatophyte species possible, although such
      methods are not available for routine practice. No elaborate technical equipment
      is needed to differentiate dermatophytes in the office. The investigator's
      mycological expertise, however, is of crucial importance. Mycological courses and
      dermato-mycological quality control are appropriate means to ensure that
      dermatologists retain their competence in treating patients with dermatophytoses.

PMID- 14968324
TI  - [Onychomycosis].
AB  - Onychomycosis is an infection of the finger-and/or toenails by fungal
      microorganisms. If untreated, the process advances and destroys the nail plate.
      It may spread to involve the skin and does not heal spontaneously. There are
      different clinical presentations of onychomycosis which vary with the nature of
      the fungus and how it invades the nail unit. These different clinical forms
      require different therapeutic approaches. The successful treatment of
      onychomycosis requires special knowledge of the various clinical presentations,
      of the differential diagnosis and of recent advances in medical mycology.
      Therefore onychomycosis is best treated by dermatologists.

PMID- 14968325
TI  - [Modern antimycotics. What the treating physician needs to know].
AB  - The treatment of dermatophytoses is a complex process influenced by the
      properties of the antimycotic and the causative agent as well as by patient
      related factors. Both the minimal inhibition concentration and the drug
      concentration in the infected tissue influence treatment success. Dermatophytes
      can be present as arthrospores in the skin, nails or hair. Non-proliferating
      dermatophytes (arthrospores) are less susceptible to antimycotics than
      proliferating ones, particularly to antibiotics which act through the inhibition
      of fungal ergosterol synthesis. Non-proliferating dermatophytes do not synthesize
      ergosterol, a essential component of fugal cell membranes. Also, dermatophytes
      accumulating in hollow spaces mostly in the nail plate, cannot be reached by
      antimycotics. The concentration of terbinafine and itraconazole is very high in
      sebum. This is of importance in the treatment of dermatophytoses localized to in
      the stratum corneum and in or around the hair. Preadolescent children do not have
      functioning sebaceous glands; this explains the difficulties in the treatment of
      pediatric tinea capitis.

PMID- 14968326
TI  - [Vulvar lichen sclerosus. The importance of early clinical and histological
      diagnosis].
AB  - Vulvar lichen sclerosus (LS) is a chronic progressive skin disease of unclear
      etiology. It is often overlooked in early stages, but progresses to destructive
      atrophy and is associated with an increased risk of vulvar squamous cell
      carcinoma. The classical symptoms are pruritus and pain, but they are often not
      distinctive, so that unclear vulvar problems often lead to a biopsy. The
      histological picture of early LS is quite different from that of late LS with an
      atrophic epidermis, markedly sclerotic dermis and stiff dilated vessels. The
      epidermis in early LS is usually normal with only minor irregularities in the
      rete pattern. The basement membrane is normal or focally widened, while the
      edematous dermis has only scattered ectatic vessels. The often dense lichenoid
      and intraepidermal infiltrate explains the spongiosis and vacuolization of the
      basal layer keratinocytes. Very early cases may only have a sparse lymphocytic
      infiltrate and hyper-/parakeratosis of the follicular ostia. Early topical
      therapy can dampen the progression to atrophic, irreversible LS.

PMID- 14968327
TI  - [Treatment of scalp psoriasis. An effective and safe tacalcitol emulsion].
AB  - BACKGROUND: The scalp is a problematic area in psoriasis where treatment is often
      difficult. The lesions often extend beyond the hairline to involve the forehead,
      neck and sensitive facial skin. Topical corticosteroids and potentially irritant
      topical preparations have only limited utility in these sensitive areas. Most of
      the patients additionally suffer from psychosocial problems due to the visibility
      of lesions. OBJECTIVE: The aim of this multicenter, prospective, randomized,
      double-blind study, was to assess efficacy, safety and tolerability of once daily
      tacalcitol emulsion (4 micro g/g) compared to placebo in the treatment of scalp
      psoriasis. METHODS: To determine efficacy, safety and tolerability, 273 patients
      with mild to moderate scalp psoriasis were treated over a 8-week period. Response
      to treatment was evaluated using the sum score of erythema, infiltration and
      scaling. Global improvement of psoriasis was rated by the investigators and the
      patients using a 5-point scale. In addition the single scores of erythema,
      infiltration and scaling were assessed by the investigators, and the patients
      were asked to evaluate the intensity of itching and scaling over the treatment
      period. RESULTS: Tacalcitol was significantly superior to placebo in reducing the
      severity of scalp psoriasis. At the end of the study, the median sum score
      decreased by 53% in the tacalcitol group and was significantly better than
      placebo with 30% (p<0.0001). Global assessment of improvement was significantly
      greater in the tacalcitol group in both investigator and patient evaluation. 80%
      of patients on tacalcitol showed improvement to clearance and was statistically
      significant better than placebo (p <0.0001) in the investigator rating after 8
      weeks. Tacalcitol was significantly superior to placebo in reducing erythema,
      scaling and infiltration, and in the patient assessment in reducing scalp scaling
      and itching. Treatment was very well tolerated. Local reactions were transient
      and uncommon. Their incidence was similar in both treatment groups. No serious
      side effects were reported, including those relating to calcium homeostasis or
      vitamin D(3) metabolism. No changes in mean levels of serum calcium, parathyroid
      hormone (PTH), calcitriol and in 24h-urinary excretion were observed. CONCLUSION:
      The results of this study indicate that topical application of tacalcitol (4
      micro g/g) emulsion once daily is an effective, safe and very well- tolerated
      treatment for scalp psoriasis.

PMID- 14968328
TI  - [Complete remission of cutaneous satellite and in-transit metastases. After
      intralesional therapy with interleukin-2 in 2 patients with malignant melanoma].
AB  - Multiple cutaneous satellite and in-transit metastases of melanoma without
      involvement of lymph nodes or other organs are a challenge especially when they
      occur in elderly inoperable patients with multiple internal diseases. In this
      particular situation, intralesional application of interleukin-2 may represent an
      effective alternative to systemic chemo- or immunotherapy as it can be performed
      on an out-patient basis and has few side effects. We treated two elderly female
      patients with multiple cutaneous metastases of malignant melanoma with intra- and
      perilesional application of interleukin-2 (3 x 6-12 Mio IE) over 12 weeks and
      achieved a complete remission of these metastases. In follow-up biopsies, no
      viable tumor cells were found. Despite a slight burning at the injection side and
      a transient local inflammatory reaction, the therapy was well tolerated in both
      cases after premedication with paracetamol 500 mg orally and pretreatment of the
      injection site with a cream containing lidocaine and prilocaine. No systemic side
      effects were observed.

PMID- 14968329
TI  - [Imiquimod, pegylated interferon-alpha-2b and interleukin-2 in the treatment of
      cutaneous melanoma metastases].
AB  - The immune system plays an important role in the defense against malignant
      melanoma. Interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) are
      therapeutically used for unspecific stimulation of the immune system. After
      intralesional injections of these cytokines into cutaneous melanoma metastases,
      regression has been observed. In view of its immunomodulating effects, imiquimod
      appears as an additional promising therapeutic option for treatment of malignant
      tumors. In a case report, we present combined therapy with intralesional IL-2,
      pegylated IFN-alpha-2b and topical imiquimod 5% cream for disseminated cutaneous
      metastatic malignant melanoma stage IIIa. This therapy achieved an almost
      complete remission. In a treatment period of eight months, side effects remained
      tolerable. Histologically, both fibrosis and inflammation were found in the
      regressing lesions. After the end of therapy, no disease progression occurred
      during 11 months follow-up.

PMID- 14968331
TI  - [The umbilical metastasis. Sister Mary Joseph and her time].
AB  - Although Baluff in 1854 and Nelaton in 1860 had already described umbilical
      metastases, the best known description of the metastasis of carcinomas to this
      site as "trouser button navel" was published in 1928 by William James Mayo (1861
      1939), son of William Worrall Mayo (1815-1911), the founder of the Mayo Clinic in
      Rochester, Minnesota, This phenomenon is supposed to have been pointed out to
      Mayo by his long-serving head surgical nurse Sister Mary Joseph (1856-1939). The
      English surgeon Hamilton Bailey, in his famous textbook "Physical Signs in
      Clinical Surgery" in 1949, coined the term "Sister Joseph's nodule" for an
      umbilical metastasis. The expression has become widely accepted and used. Sister
      Mary Joseph, daughter of Irish immigrants, belonged to the 3rd order of the Holy
      Francis, was distinguished for her skills, intelligence and devotion to nursing
      which was also her calling. She worked for many decades at the world-famous Mayo
      Clinic and taught generations of young nurses. In recent years, the original
      surgical building at Saint Mary's Hospital has been named "Joseph Building" in
      her memory. Among the numerous eponyms occurring in the dermatology and the
      medicine, the association with the name of a nurse represents beyond doubt a
      special feature.

PMID- 14968330
TI  - [Anaplastic large cell lymphoma and keratoacanthoma].
AB  - In CD30 positive lymphoproliferative disorders, e.g. anaplastic large cell
      lymphoma (ALCL) and lymphomatoid papulosis (LyP), pseudoepitheliomatous
      hyperplasia may occur in up to 50 percent of the cases. Epithelial tumors are
      rarely associated with ALCL or LyP, but the presence of single CD30 positive
      cells among the infiltrate accompanying epithelial tumors such as basal cell
      carcinomas and keratoacanthomas is well known. A 66-year-old man developed within
      a plaque of ALCL a rapidly growing epithelial tumor which we classified according
      to the clinical and histological features as keratoacanthoma. This case
      underlines the intimate interaction between CD30 positive lymphocytes and
      epithelial cells.

PMID- 14968332
TI  - [Painful symmetrical ankle ulcerations. A 73-year old patient with chronic
      myeloid leukemia].

PMID- 14968333
TI  - [Therapy of syphilis].

PMID- 14968335
TI  - [Similar, but not the same: peripheral and coronary vascular disease].

PMID- 14968336
TI  - [Atherosclerosis and arteriitis: implications for therapy of cardiovascular
      disease].
AB  - Cardiovascular disease, the most common cause of death in the Western world,
      results mainly from atherosclerotic remodeling of the arterial system.
      Atherosclerosis defines a disease in which the arterial wall becomes thickened
      and loses elasticity. This is clearly not a static condition. Instead,
      atherogenesis reflects a continuous development over time, ranging from
      macroscopically intact arteries to ruptured sclerotic plaques. Different stages
      at different sites can be present simultaneously within one individual. The
      pathophysiology of atherogenesis comprises various important steps, including
      enhanced endothelial permeability, expression of adhesion molecules, monocyte
      adhesion and immigration, foam cell formation, fatty streaks, smooth muscle cell
      migration and plaque formation, and, finally, plaque rupture and thrombus
      formation. In recent years, atherosclerosis is more and more being recognized as
      a chronic inflammatory process. The hypothesis of a chronic inflammation in
      atherosclerosis is supported by the following findings: atherosclerosis is
      associated with enhanced serum levels of inflammation parameters, including in
      particular C-reactive protein (CRP, Table 1); the atherosclerotic artery produces
      different hydrolytic enzymes, adhesion molecules, cytokines, and growth factors
      as seen in chronic inflammation; cells found in early atherosclerotic lesions are
      typically inflammatory cells (monocytes/ macrophages and T-lymphocytes); and,
      there is convincing clinical and experimental evidence that formation of reactive
      oxygen species (ROS) is augmented during this chronic inflammatory process due to
      an imbalance between synthesis of ROS and neutralizing antioxidative defense
      mechanisms. Studies in the general population could clearly show that markers of
      inflammation, in particular CRP, predict the cardiovascular risk. It is the aim
      of this review to discuss the role of inflammatory processes for the development
      of atherosclerosis and cardiovascular disease. Pro-inflammatory substances
      contributing to oxidative stress are listed in Table 2, and particular emphasis
      is placed on pathophysiologic effects induced by oxidized LDL and angiotensin II.
      Figure 1 summarizes important reaction steps of oxidative stress reactions, based
      on formation of superoxide anion (O(2)(-)). Finally, therapeutic options are
      presented, although it has to be emphasized that treatment with antibiotics
      proved to be essentially ineffective, and treatment options with antioxidants are
      not sufficiently evaluated to allow a final statement. Meanwhile, however, there
      is accumulating evidence that established treatment regimens with statins or
      renin-angiotensin system inhibitors possess profound anti-inflammatory and
      antioxidative properties which may support their beneficial effects on
      cardiovascular disease.

PMID- 14968337
TI  - [Role of lipid lowering therapy in patients with peripheral arterial occlusive
      disease].
AB  - BACKGROUND: Peripheral arterial occlusive disease (PAOD) is common in older age.
      PAOD is associated with an increased risk of vascular events (e. g. myocardial
      infarction or stroke). Therefore, the prevention and treatment of PAOD is
      important, especially at a time when the elderly population is increasing. There
      is an association between lipid abnormalities and the risk of developing PAOD.
      However, it is not yet definitively established if early intervention with lipid
      lowering drugs prevents the development of PAOD and improves outcome. RESULTS OF
      STUDIES: In a 5-year follow-up study, in which hypercholesterolemia was treated
      by partial ileal bypass (POSCH study), the incidence of claudication was reduced
      to 19% (n = 126) in the surgical treatment group vs. 33.6% (n = 119) in the
      control group (p < 0.01). Direct imaging of peripheral atherosclerosis was not
      performed and a partial ileal bypass operation is followed by considerable
      changes in nutrition. A 2-year follow-up study of 153 patients with femoral
      atherosclerosis treated with colestipol-niacin demonstrated a decreased
      progression of angiographically assessed femoral atherosclerosis (p < 0.02). A
      subgroup analysis of the Scandinavian Simvastatin Survival Study (n = 4,444)
      reported worsening symptoms in 3.6% in the placebo group as compared to 2.3% in
      the simvastatin group (p = 0.008). In an open trial lipid-lowering therapy with
      statins did not improve functional outcomes including 6 minutes walking distance
      and 4 minutes walking velocity in 392 men and women with an ankle-brachial-index
      (ABI) < 0.90. A summary performance score combined performance in walking speed,
      standing balance, and time for five repeated chair rises into an ordinal score
      ranging from 0 to 12 (12 = best) was improved (p < 0.001). A randomized placebo
      controlled prospective study with simvastatin including 43 patients in each group
      demonstrated an improved painfree and total walking distance as well as an
      increased ABI after 6 months. A second placebo controlled study investigated the
      effect of 10 mg and 80 mg atorvastatin in 354 patients after 12 months. Painfree
      walking time was only improved by 80 mg atorvastatin, maximum walking time and
      ABI remained unchanged. A questionnaire regarding physical activity showed
      improved results already for 10 mg atorvastatin, whereas quality of life did not
      change. Pathomechanistic explanations, such as regression of peripheral
      atherosclerosis, were not described. CONCLUSION: All in all the association
      between the progression of PAOD and lipid abnormalities is surprisingly
      inconclusive and the effects of lipid-lowering are not defined. Well designed
      long-term studies assessing primary and secondary prevention of PAOD with defined
      endpoints, such as amputation rate or number of vascular interventions are
      missing. The mechanisms improving physical activity whithout affecting PAOD
      outcome have to be investigated.

PMID- 14968338
TI  - [Noninvasive methods in the diagnosis of macro- and microangiopathy of
      peripherial and carotid arteries].
AB  - PURPOSE: Indications and diagnostic value of the most important noninvasive
      procedures for the diagnosis of peripheral arterial disease and diseases of the
      supraaortic arteries are reviewed in this article with particular emphasis on
      cardiologic questions. PERIPHERAL ARTERIAL DISEASE: As compared to coronary
      artery disease, peripheral arterial disease has long been addressed as being
      negligible in number and importance, a view that had to be reassessed in recent
      years. The prevalence of claudication and critical leg ischemia has increased.
      Earlier diagnosis and specific therapeutic regimens will be able to prevent or at
      least slow progression of the disease and, thereby, major amputation. The
      patient's history and physical examination in addition to measurement of the
      ankle-brachial index (ABI; determined by dividing the systolic pressure measured
      by Doppler ultrasonography of the A. dorsalis pedis or A. tibialis posterior by
      that of the A. brachialis) usually allows for the diagnosis of peripheral
      arterial disease (ABI < 0.9). If in doubt (ABI > 0.9, but presence of typical
      claudication), a treadmill test or additional tests such as pressure-pulse
      recording (mechanical oscillography), toe pressure measurements, or duplex
      ultrasonography should be performed. When peripheral arterial disease has been
      diagnosed, duplex ultrasonography or treadmill testing aids in planning
      additional diagnostic procedures and the adequate therapeutic regimen.
      Transcutaneous oxymetry is of prognostic value in assessing the tendency of wound
      healing in distal limb ulceration and can distinguish between critical limb
      ischemia and complicated claudication. Thermography is used to document
      functional and organic peripheral arterial occlusions and capillaroscopy to
      directly view nail fold capillaries in order to distinguish between primary and
      secondary Raynaud's phenomenon. Noninvasive radiologic techniques in the
      diagnosis of peripheral arterial disease are also discussed in this journal.
      SUPRAAORTIC ARTERIES: Noninvasive diagnostic procedures in assessing disease of
      the supraaortic arteries include history-taking, physical examination, continuous
      wave-(cw-)Doppler and color-coded ultrasonography. Cw-Doppler ultrasonography is
      still widely used and sufficient in diagnosing moderate to severe stenosis or
      occlusion of the carotid artery. B-mode and color-coded ultrasonography has
      several advantages over cw-Doppler ultrasonography through direct visualization
      of the vascular membrane, perivascular structures, and intravascular blood flow.
      Carotid stenosis < 50% and plaque morphology can be assessed, inflammatory
      processes, aneurysms, and dissections diagnosed. Increase in intima-media
      thickness and echolucent plaques are associated with cerebral ischemic events and
      can be diagnosed via duplex sonography. These findings have great implications in
      the consultation of patients with atherogenic risk factors.

PMID- 14968339
TI  - [Autoantibodies and peripheral arterial occlusive disease].
AB  - BACKGROUND: In patients with early manifestation of peripheral arterial occlusive
      disease (PAOD) and a less classical atherosclerotic risk profile, vasculitis is
      presumed to be the underlying disease. We performed a prospective study of the
      importance of determination of autoantibodies used for the diagnosis of
      vasculitis and collagen diseases in patients with symptomatic PAOD. PATIENTS AND
      METHOD: 698 consecutive patients (mean age +/- SD: 68 +/- 10 years) were included
      who were referred from 1998 to 1999 for interventional treatment of PAOD. In 121
      PAOD-patients (61 +/- 12 years) with a less pronounced atherosclerotic risk
      profile, or rarefied distal arteries without sclerosis of the media, or elevated
      erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) independent from
      the stage IV of PAOD, the following autoantibodies were investigated: antinuclear
      antibodies (ANA), antibodies against extractable nuclear antigens (ENA): SCL 70,
      RNP, SS-A, SS-B, Jo-1, SM), double-stranded DNA antibodies (ds-DNA),
      antineutrophil cytoplasmatic antibodies (c- and p-ANCA), antiphospholipid
      antibodies [phosphatidylserine (APSA) and beta(2)-glycoprotein], smooth (SMA) and
      striated muscle (StrMA). ANA, SMA and StrMA were estimated by indirect
      immunofluorescence technique, ENA by Western-blot and the others by enzyme linked
      immunoassay. RESULTS: 38 PAOD-patients (35%) had increased autoantibody
      concentrations. The rate of different PAOD stages and localization did not differ
      between the group of patients with increased autoantibody concentrations and the
      group of patients without. But the group of patients with increased autoantibody
      concentrations had higher rates of elevated ESR [p-value of 0.0043, odds ratio of
      7.1 (95% CI: 1.49-33.81)]. ANA were the most frequent autoantibodies detected in
      17 (14%) of the 121 patients followed by APSA and autoantibodies directed against
      beta(2)-glycoprotein. During follow-up of 24 +/- 6 months no vasculitis or
      collagen diseases associated with the elevated autoantibody concentrations became
      clinically manifest in the 38 patients. Two patients died due to coronary heart
      disease. Four patients had a worsening of their PAOD but no amputation was
      performed. Out of the 83 patients without elevated concentrations of
      autoantibodies, eight patients died and three amputations were carried out.
      CONCLUSION: All in all, increased autoantibody concentrations in patients
      suffering from peripheral atherosclerosis are not a rare finding. A systematic
      determination of autoantibodies, especially in patients with a low
      atherosclerotic risk profile, does not increase the number of manifest or
      developing vasculitis of collagen disease.

PMID- 14968340
TI  - [MR-Imaging of lower leg muscle perfusion].
AB  - PURPOSE: This article describes the potential of dynamic contrast- enhanced
      magnetic resonance tomography (DCE-MRT) for the visualization and quantification
      of blood flow of lower leg muscles at rest and after individually adjusted
      muscular exercise. PATIENTS AND METHODS: Five cases were chosen to exemplify the
      qualitative and semi-quantitative blood flow evaluation in the lower leg muscles.
      The crural muscle state was determined with an isometric maximal strength
      measurement from a female patient with peripheral arterial occlusive disease
      (pAVK), a male patient with coronary heart disease (KHK) without clinical signs
      of a pAVK, a volunteer with sufficient physical activity in accordance with the
      Freiburg Questionnaire of Physical Activity and two professional athletes. After
      calibration of the plantarflexion ergometer MR-PEDALO (Figures 2a and 2b) for the
      execution of auxotonic muscle work a 1- minute alternating foot extension and
      flexion exercise on MRPEDALO was performed in the MR machine. Instead of the
      lower leg splint shown in Figures 2a and 2b the MR coil fits exactly in MR-PEDALO
      used for DCE-MRT. Mechanical work performed during the 1-minute exercise ranged
      from 52 watt seconds (Ws) to 244 Ws (0.65 W to 4.07 W), indicating similar
      interindividual work loads in relation to the individual maximum isometric
      strength. DCE-MRT was performed at rest and immediately after auxotonic exercise
      test (T1w 2DFLASH- GE sequence with TR/TE/alpha: 100 ms/6 ms/70 degrees; field of
      view: 400; matrix: 81 x 256; slice thickness: 10 mm; acquisitions: 73 at 8.3 s
      each; total examination time: 9.24 min; bolus application of Magnevist, Schering,
      0.02 ml/kg kg, 20 ml bolus NaCl, flow 2 ml/s, 22G cannula in a cubital vein).
      Signal intensity (SI) curves were analyzed with DynaVision (MeVis gGmbH, Bremen,
      Germany). RESULTS: Measuring peripheral blood flow needs appropriate muscular
      stress tests. The SI-curves of the region of interest (ROI) representing the
      peroneus, tibialis anterior and gastrocnemius muscle run almost parallel at rest.
      Workloads between 52 Ws and 244 Ws (0.65 W and 4.07 W), similar in relation to
      the individual maximum isometric strength, induce distinctive changes of the
      upslope, wash-in, peak and washout of SI-curves preferably for the peroneus
      muscle and less predominant also for the tibialis anterior muscle and
      gastrocnemius muscle respectively. The first case, a 55-year-old female patient
      with peripheral arterial occlusive disease (pAVK) stage Fontaine IIb before
      (Figure 3a) and after (Figure 3b) percutaneous transluminal angioplasty (PTA) of
      a right femoral artery stenosis shows after interventional treatment a rapid post
      exercise SI-increase in the peroneus muscle. The steeper SI-curve indicates a
      better contrast medium inflow due to an improved perfusion. The second case, a 65
      year-old man suffering from coronary heart disease without clinical signs of pAVK
      (Figure 4) exercised with a workload of 92 Ws. After stress test the ROI for the
      peroneus muscle shows a clear intensity increase. After exercise the SI-curve for
      the tibialis anterior muscle shows a similar, but less predominant change while
      the shape of the SI-curve of the gastrocnemius muscle remains mainly identical. A
      23-year-old male person with average physical activity (Figure 5) performed DCE
      MRT of the left lower leg after stress test with 172 Ws demonstrating a rapid
      signal increase in the peroneus muscle while the synergistic tibialis anterior
      muscle and antagonistic gastrocnemius muscle show a comparatively slow contrast
      medium wash-in. A 26-year-old male athlete (Figure 6) exercised with 196 Ws
      showing a rapid contrast medium inflow in the peroneus muscle and initially also
      in the synergistic tibialis anterior muscle. A contrast-medium wash-out appears
      in both muscles, while the shape of the gastrocnemius muscle SI-curve remains
      substantially unchanged. A 26-year-old female athlete (Figure 7) exercised with
      244 Ws. Post exercise SI-curves show a distinctive and rapid increase of contrast
      medium wash-in with a sharp peak particularly in the peroneus muscle and
      similarly in the tibialis anterior and gastrocnemius muscle. After exercise all
      SI-curves show a wash-out phase. CONCLUSION: SI-curves show relative increase in
      correlation with Time-to-Peak (TTP) decrease and Mean-Intensity to Time Ratio
      (MITR) increase indicating blood flow reserve mobilization after exercise.
      Individual muscle state seems to be linked to muscle recruitment and muscle
      coordination reflected by post-exercise SI-curves. The gastrocnemius muscle shows
      comparatively low SI-curve changes after muscular load test. Further
      methodological standardization and optimization of the stress test is mandatory
      to assure intra- and interindividual comparisons. Due to direct visualization and
      quantitative evaluation of the peripheral microcirculation DCE-MRT has a
      diagnostic potential for monitoring therapeutic response in peripheral
      circulation disorders and sports medicine.

PMID- 14968341
TI  - Wegener's granulomatosis.
AB  - Wegener's granulomatosis is an organ- and/or life-threatening autoimmune disease
      of as yet unknown etiology. The classic clinical triad consists of necrotizing
      granulomatous inflammation of the upper and/or lower respiratory tract,
      necrotizing glomerulonephritis, and an autoimmune necrotizing systemic vasculitis
      affecting predominantly small vessels. The detection of antineutrophil
      cytoplasmic antibodies directed against proteinase 3 (PR3-ANCA) is highly
      specific for Wegener's granulomatosis. ANCA positivity is found only in about 50%
      of the patients with localized Wegener's granulomatosis (which is restricted to
      the respiratory tract and affects < or = 5% of the patients), whereas PR3-ANCA
      positivity is seen in 95% of the patients with generalized Wegener's
      granulomatosis. Studies showing an expansion of circulating tumor necrosis factor
      (TNF-)alpha-producing Th1-type CD4(+)CD28(-) T-cell effector memory T-cells and
      their presence as Th1-type cytokine profile- driving cell population within
      granulomatous lesions provide the rationale for using TNF-alpha-blocking agents
      in Wegener's granulomatosis refractory to standard induction therapy with
      cyclophosphamide and corticosteroids ("Fauci's scheme"). Vasculitis is an
      independent risk factor for diffuse endothelial dysfunction and may be a
      consequence of TNF-alpha action on endothelial cells. Recently, another study has
      shown intima-media thickening of the wall of the common carotid artery and bulb,
      as well as a significantly increased incidence of stroke, myocardial infarction
      and occlusive artery disease in Wegener's granulomatosis. This study suggests
      that systemic inflammation and vasculitis contribute to accelerated
      arteriosclerosis in Wegener's granulomatosis.

PMID- 14968342
TI  - [Interventional therapy of peripheral arterial disease-potentials and
      limitations].
AB  - The technical success rate of endovascular interventions in order to improve
      perfusion in peripheral arterial disease in the lower extremities has been
      markedly improved in the last decade due to clinical application of new
      recanalization techniques like application of hydrophil-coated guide wires,
      implantation of stents or stent grafts. If the-even long-segment-obstruction can
      be recanalized, the interventional radiologist is able to open the arterial
      vessel sufficiently. The excellent immediate results are limited in the long term
      by recurrent stenoses, which appear in different rates according to the vascular
      region. Whereas recurrent stenoses have nearly no clinical significance in the
      aortoiliac vascular segment due to the size of the treated vessels and the
      excellent flow, there is a significant amount of restenoses in the
      femoropopliteal segment and, even more, in the tibial arteries. This leads to a
      different indication of endovascular therapy according to the segment treated.
      However, in an interdisciplinary consensus we offer primary endovascular therapy
      for treatment of aortoiliac obstruction to all patients, whereas lesions at the
      femoral bifurcation are a clear primary indication for open surgical treatment.
      In the femoropopliteal segment, we choose a primary endovascular procedure with
      respect to the length of the occlusion, patient's risk factors and comorbidities.
      Yet, longer obstructions are a clear indication for primary surgical treatment.
      In cases of infrapopliteal disease, we recommend an endovascular treatment as the
      initial option due to the reduced invasiveness of the predominantly old and
      multimorbid patient cohort. Further clinical research for the evaluation of
      endovascular therapeutic measures in peripheral arterial disease urgently
      requires outcome studies, which include clinically relevant endpoints to better
      define the clinical value of endovascular therapy compared to traditional
      surgical bypass procedures. Until new clinical trials will be published, the
      Transatlantic Consensus document (TASC) of a variety of vascularly specialized
      scientific societies seems to be a helpful guideline.

PMID- 14968343
TI  - Treating renal artery stenosis. A statement pro endovascular therapy.
AB  - Renal artery stenosis (RAS) leading to hypertension or ischemic nephropathy can
      be treated by endovascular revascularization using balloon angioplasty or stent
      implantation. Although high technical success rates > 95%, relatively low
      frequencies of complications and good long-term patency can be achieved, the
      indications for interventional treatment are a matter of ongoing debate. Curing
      hypertension by means of angioplasty rarely occurs, although the number of
      antihypertensive medication usually can be reduced after successful treatment.
      Targeting ischemic nephropathy, revascularization can stabilize or at least slow
      the decline of renal function. Nevertheless, angioplasty also bears the risk of
      inducing renal deterioration. Careful patient selection remains the most crucial
      point in renal interventions, however, current data are insufficient to give
      final recommendations on this issue. The present review focuses on the potential
      beneficial effects of renal artery PTA and stenting in patients with RAS.

PMID- 14968344
TI  - [Management of patients with renal artery stenosis. Reappraisal of operative
      treatment].
AB  - Arterial hypertension is most often the first symptom of renal artery stenosis
      (RAS). Appropriate screening methods for the diagnostic workup of hypertension
      are colour-coded duplex ultrasound and captopril scintigraphy. Angiography
      (intraarterial digital subtraction angiography) represents the diagnostic "gold
      standard", which is the prerequisite for the selection of the most suitable
      therapeutic method. Atherosclerosis is the most common disease in elderly
      patients presenting with RAS. In younger patients, fibromuscular dysplasia is
      more frequent. Five main types with different prognosis and therapeutic
      indications can be classified. Rare causes of RAS are dissection, renal artery
      aneurysm with combined stenosis, and especially in children and adolescents
      middle aortic syndrome with hypoplasia of the visceral arteries. Every patient
      with RAS of hemodynamic relevance in the presence of hypertension should be
      treated, whereas therapeutic risk and benefit must be weighed up individually.
      Aims are the improvement of hypertension and the maintenance of renal function.
      Surgical techniques, which are described subsequently, are indicated in all
      patients who need further simultaneous treatment of the abdominal vessels
      (abdominal aortic aneurysm, aortoiliac or visceral artery stenosis or aneurysm,
      respectively). In atherosclerotic ostial stenoses, angioplasty (PTA) and open
      surgery (normally transaortic endarterectomy) are concurrent methods. In our
      experience, the long-term results of surgical reconstruction seem to be superior.
      Both procedures are subject to an ongoing randomized study in our department. The
      outcome of surgical treatment for RAS is satisfying, the operative risk
      especially in isolated renal artery lesions is negligible.

PMID- 14968345
TI  - [Treatment of carotid stenosis: carotid surgery or stent? In favor of operation].
AB  - BACKGROUND: According to international studies (ACAS, NASCET, ECST, ACST) the
      discussion concerning the indication for an operative treatment of carotid artery
      stenosis which lasted over years, may be regarded as completed. The impressive
      results showed that the operative treatment is of less risk for the patient than
      the natural history. But is this conclusion also true for carotid artery
      stenting? Comparative studies are running, but are not completed yet. The
      treatment of carotid stenosis by operative or interventional means is
      controversial, since conflicting conclusions have been drawn from the correlation
      between plaque morphology and the patients' embolic risk. We clearly recommend
      treatment by carotid endarterectomy and discourage angioplasty and stenting
      except in controlled and randomized studies. METHODS AND RESULTS: In a
      prospective study of patients with carotid artery stenoses, we compared plaque
      morphology, as examined by ultrasound, with the histological diagnosis. We found
      that plaque morphology (soft vs. hard plaques) cannot adequately predicted, since
      in only 80% of cases the noninvasively suspected plaque morphology could be
      confirmed. In contrast, the accuracy for the estimation of the degree of stenosis
      was excellent with 98%. In the case of stroke in progression and completed
      stroke, histological examination found ulcerations in 72% of patients, whereas
      ultrasound had detected these ulcerations in only 53%. A significantly higher
      number of transient ischemic attacks and strokes occurred in patients with soft
      plaques as compared to asymptomatic patients, who tend to present with hard
      plaques. Patients with soft plaques seem to have a higher risk of postoperative
      permanent neurological deficit. Dangerous plaque formation with thrombotic or
      ulcerous material was not accurately detected by ultrasound. Therefore the risk
      of embolisation cannot be predicted efficiently by means of duplex scanning,
      which, however, is especially important for carotid stenting. High intensity
      transient signals (HITS) were detected by transcranial Doppler during carotid
      endarterectomy and carotid stenting. A significant higher number of HITS was
      found in dangerous plaque formations like ulcerations or thrombotic formations.
      The number of HITS during carotid angioplasty and stenting was eight to ten times
      higher than in the worst group during operation. CONCLUSION: Due to the
      insufficient knowledge about the benefit of carotid stenting, these observations
      are indicating that surgery on the carotid artery is not comparable to
      interventional treatment and remains the gold standard, until the results of
      prospective randomized trials will demonstrate an equivalent outcome.

PMID- 14968346
TI  - [Diabetic foot syndrome].
AB  - PATHOGENETIC FACTORS: The decisive factors for the etiology of the diabetic foot
      syndrome (DFS) are diabetic neuropathy, macroangiopathy and the combination of
      neuropathy with macroangiopathy. If ischemia prevails, macroangiopathy decisively
      deteriorates the prognosis and leads, together with local infection, to
      amputation in almost all cases of DFS. Triggering factors are exogenous trauma by
      tight shoes, foreign bodies and insufficient foot care combined with a foot
      deformity, which develops in the context of osteoarthropathy. Pathogenetic
      factors include the increased collagen deposition and network by advanced
      glycosylation endproducts, the loss of adipose tissue and the occurrence of
      edema, which destroy the compensating balance between preventive and damaging
      factors. THERAPY: Regular routine inspections by the physician and the patient
      for hyperkeratosis, fungal infection, skin lesions, control of footwear and foot
      deformities are as indispensable as the examination of the neurologic and
      angiologic status. Treatment requires the know-how of a specialized center in
      collaboration of different medical disciplines, e. g., the diabetologist, the
      angiologist, the orthopedic and vascular surgeon, the interventional radiologist
      and assistance by the podiatrist, the orthopedic technician and expert diabetic
      counseling. Whereas the neuropathic lesion almost always heals under local
      therapy and pressure release, ischemic lesions demand revascularization. A
      superimposed infection calls for microbial and resistance testing, since up to
      six different agents including anaerobic bacteria can be found. This situation
      needs systemic antibiotic therapy and local treatment. PROPHYLAXIS: The
      amputation rate can be considerably reduced by these measures. Even more
      important is structured teaching of the patient, which can reduce amputation by
      60-70%, which underlines the importance of prophylaxis in DFS. Teaching to the
      patient must comprise daily inspection of the feet, correct hygiene of the feet
      and adequate footwear.

PMID- 14968347
TI  - [Therapy with NO donors-antiatherogenic and antioxidant actions].
AB  - Nitric acid esters such as glyceryl trinitrate were introduced into therapy more
      than a century ago and are still widely used for the treatment of myocardial
      ischemia and its main symptom angina pectoris. The basic mechanisms responsible
      for the vasodilatory and anti-ischemic action of organic nitrates involve
      bioactivation of, and nitric oxide (NO) release from, these compounds which have
      therefore been termed NO donors. The organic nitrate pentaerythritol tetranitrate
      (PETN) is known to possess antioxidant properties that are thought to be the
      underlying cause for its specific pharmacological profile. In contrast to other
      long-acting nitrates, PETN induces tolerance- free vasodilation in humans and was
      reported to prevent endothelial dysfunction as well as atherogenesis in
      cholesterol- fed rabbits. However, the exact nature of the vasoprotective
      signaling pathways triggered by PETN has remained obscure. The present study
      demonstrates that the active PETN metabolite PETriN stimulates protein expression
      of the antioxidant defense protein heme oxygenase-1 (HO-1; Figures 1 and 2).
      Additionally, PETriN enhanced the enzymatic activity of HO-1 measured as
      formation of the HO-1 metabolites bilirubin (Figure 3) and carbon monoxide
      (Figure 4) in lysates from endothelial cells. HO-1 induction subsequently led to
      a marked increase in protein expression of a second antioxidant protein,
      ferritin, via the HO-1-dependent release of free iron from endogenous heme
      sources (Figures 1 and 5). Pretreatment of endothelial cells with PETriN was
      followed by increased cellular resistance to oxidant injury mediated by hydrogen
      peroxide (Figure 6). Endothelial protection by PETriN was mimicked by exogenous
      bilirubin which led to an almost complete reversal of hydrogen peroxide-induced
      toxicity (Figure 8). Increased HO-1 and ferritin expression as well as
      endothelial protection occurred at micromolar concentrations of PETriN which are
      well within the range of plasma or tissue levels that can be expected during oral
      therapy. The capacity to protect the endothelium in vitro may translate into and
      explain the previously observed antiatherogenic actions of PETN in vivo. In this
      study, another long-acting nitrate, isosorbide dinitrate (ISDN), did not protect
      endothelial cells from oxidant damage (Figure 6). The absence of significant
      cytoprotection in the presence of ISDN was paralleled by a lack of HO-1 and
      ferritin stimulatory capacity (Figures 2 and 5). ISDN had no significant effect
      on carbon monoxide release or bilirubin formation (Figures 3 and 4). These
      observations are in agreement with results demonstrating small or nondetectable
      amounts of NO released from ISDN and its active metabolite isosorbide mononitrate
      (ISMN) measured as cyclic GMP formation in RFL-6 reporter cells (Figure 7).
      Interestingly and in contrast to PETN, isosorbide nitrates are known to induce
      tolerance to their cardiovascular effects, presumably via oxidant stress.
      Moreover, in earlier investigations aimed at assessing the antiatherogenic
      potential of nitrates, PETN but not isosorbide nitrates prevented plaque
      formation and endothelial dysfunction in animal models of atherosclerosis. Thus,
      the ability to activate HO-1 induction and associated antioxidant pathways
      apparently distinguishes PETN from other long-acting nitrates and may explain
      their different patterns of action in vivo (Figure 9).

PMID- 14968348
TI  - Ruptured abdominal aortic aneurysm. Predictors of survival in 229 consecutive
      surgical patients.
AB  - BACKGROUND AND PURPOSE: A ruptured abdominal aortic aneurysm is one of the most
      urgent surgical conditions with high mortality. The aim of the present study was
      to define relevant prognostic predictors for the outcome of surgical treatment.
      PATIENTS AND METHODS: This study included 229 subsequent patients (83% males, 17%
      females, age 67.0 +/- 7.5 years) with a ruptured abdominal aortic aneurysm.
      Before surgery, all patients underwent clinical examination, ultrasonography was
      performed in 78.6% (mean aneurysm diameter 73 mm, range 40-100 mm), computed
      tomography (CT) scan in 16.2%, magnetic resonance imaging (MRI) in 0.9%, and
      angiography in 12.6% of patients. The aneurysm was infrarenal in 74%, juxtarenal
      in 12.3%, suprarenal in 6.8%, and thoracoabdominal in 6.8% of patients. Types of
      rupture were retroperitoneal (65%), intraperitoneal (26.8%), chronic (3.8%),
      rupture into vena cava inferior (3.2%), and into duodenum (0.6%). Reconstruction
      included interposition of Dacron graft (53%), aortobiiliac bypass (32.8%), and
      aortobifemoral bypass (14.2%). RESULTS: Findings on admission that significantly
      correlated with both intraoperative (13.5%) and total intrahospital mortality
      (53.7%) were: systolic blood pressure < 95 mmHg, low diuresis, unconsciousness,
      cardiac arrest, leukocytes > 14 x 10(9)/l, hematocrit < 0.29%, hemoglobin < 100
      g/l, urea > 11 mmol/l, and creatinine > 180 micro mol/l. Intraoperative
      determinants of increased mortality were: aortic cross-clamping time > 47 min,
      duration of surgery > 200 min, intraoperative blood loss > 3,500 ml, diuresis <
      400 ml, arterial systolic pressure < 97.5 mmHg, and the need for aortobifemoral
      bypass. Respiratory complications and multisystem organ failure were associated
      with a lethal outcome in the postoperative period. CONCLUSION: Surgical treatment
      of ruptured abdominal aortic aneurysm was life-saving in 46.3% of patients.
      Hypotension, low diuresis, high urea and creatinine levels, signs of blood loss,
      unconsciousness, cardiac arrest, and the need for aortobifemoral reconstruction
      predicted poor outcome. Short aortic cross-clamping and total operation time, low
      intraoperative blood loss, and well-controlled diuresis and arterial pressure
      during surgery have improved survival.

PMID- 14968349
TI  - Echocardiographic diagnosis of ischemic ventricular septal defect in a patient
      with acute myocardial infarction.

PMID- 14968351
TI  - [Lifestyle modification - is it worth it?].
AB  - BACKGROUND: The Western lifestyle contributes significantly to the high
      prevalence of coronary artery disease in Western nations. Smoking, a fat-loaded
      diet, low physical activity, obesity, diabetes, increased alcohol consumption
      contribute in a variable combination to the incidence and progression of coronary
      artery disease. The conventional risk factors are responsible for > 80% of
      cardiovascular events. Coronary artery disease is therefore a highly preventable
      disease. Randomized studies evaluating changes and lifestyle are difficult to
      conduct. Lifestyle is in many respects not governed by the intellect but the
      result of education, life long habits and possibly also genetically determined.
      Nevertheless, there is increasing evidence that modification of life style has a
      significant influence on the incidence and the course of coronary artery disease.
      SMOKING: Smoking is responsible for 50% of all avoidable death. There is a
      significant relation between the number of smoked cigarettes and the increase of
      cardiovascular risk. Despite the lack of randomized end point studies there is
      universal agreement that the advise for smoking cessation is a class-1
      recommendation. NUTRITION: Prospective studies on different components and
      principles of nutrition (Western vs. Mediterranean diet) demonstrate a
      significant influence of the diet on the development of coronary artery disease
      and sudden death. Several randomized studies show evidence that consumption of
      fish or a Mediterranean diet have a significant influence on the improvement of
      prognosis. WEIGHT: There is a correlation between weight and cardiovascular
      disease and cardiovascular death. A body mass index of > 30 doubles the incidence
      of sudden death. A moderate increase of body mass index quadruples the risk for
      diabetes in males, in females the risk is 8-fold increased. Weight reduction
      improves endothelial function and decreases systemic inflammatory reaction.
      PHYSICAL ACTIVITY: There is a significant inverse relation between physical
      fitness or habitual physical activity on the one hand, and the incidence of
      coronary artery disease on the other hand. Physical activity improves exercise
      capacity, decreases angina pectoris and decreases cardiac events and hospital
      admissions after PTCA. Physical activity also decreases insulin resistance and
      delays the occurrence of diabetes. ALCOHOL CONSUMPTION: Moderate alcohol
      consumption was associated with a decrease of cardiovascular events in patients
      with increased cardiovascular risk. Nevertheless, alcohol consumption in the
      population is a significant source for avoidable premature death. CONCLUSION: The
      knowledge resulting from observational studies on the importance of lifestyle for
      the development of coronary artery disease is increasingly validated by
      prospective randomized studies. Despite the fact that much more research needs to
      be done the recommendation for improvement of lifestyle in terms of increasing
      physical activity decreasing overweight, using a Mediterranean diet and smoking
      cessation are class-1-recommendations. A nationwide improvement in lifestyle
      could result in a significant decrease in health care expenditures and could also
      have an important role in preventing or delaying coronary artery disease.

PMID- 14968352
TI  - Phenotypic alterations in Arabidopsis thaliana plants caused by Rhodococcus
      fascians infection.
AB  - Arabidopsis thaliana (L.) Heynh. plants were challenged with Rhodococcus fascians
      at several developmental stages and using different inoculation procedures. A
      variety of morphological alterations was scored on the infected plants; some of
      them resembled phenotypes of A. thaliana mutants in their shoot apical meristem
      (SAM) organization. Infection with R. fascians did not affect SAM organization in
      wild type nor in SAM mutants. Anatomical studies on the new organs formed after
      infection with R. fascians demonstrated extensive bacterial colonization.
      Colonization and concomitant production of specific signals are the likely cause
      of malformations.

PMID- 14968353
TI  - Retention of lepirudin at the tip of a silicone catheter: a better catheter flush
      solution?
AB  - Because central venous catheters often become blocked by clot at their tip
      despite heparin flushes, a more effective anticoagulant is needed. We hypothesize
      that lepirudin, a recently introduced protein anticoagulant, might be more
      effective than heparin because of its tendency to adsorb to silicone, a commonly
      used catheter material. We preliminarily tested this hypothesis in vitro by
      measuring residual lepirudin and heparin activity at the tip of a catheter that
      had been submerged in a flowing stream of water for various periods of time. We
      observed that lepirudin is less readily removed than heparin from the catheter by
      fluid washing over it. This "slow-release" property of lepirudin might provide
      prolonged protection against clot formation at the catheter tip. A clinical trial
      will be necessary, however, to determine whether this property translates into
      significant improvement in catheter function.

PMID- 14968354
TI  - Environmental variables for modeling wheat yields in the southwest pampa region
      of Argentina.
AB  - Two types of time scales--10-day intervals (D) and phenological phases (P)--were
      applied to environmental variables for the development of statistical regression
      models relating to the southwest pampa region of Argentina, with the aim of
      detecting the effects of weather on wheat yields for the period 1977-1999. The
      parameters were grouped as meteorological and processed variables and indices.
      The processed variables used were total soil water availability (SWA) and the
      ratio of actual evapotranspiration to potential evapotranspiration (alpha),
      obtained from a water-balance model in which the moisture anomaly index (Z) and
      the Palmer drought severity index (PDSI) were calculated according to Palmer's
      model. For these parameters it was possible to establish the times of year and
      the phenological phases with the best correlation to grain yield. The regression
      equation for meteorological variables on a 10-day scale provides one of the best
      fits. Using mixed parameters, the two models, D and P, give rise to a standard
      error of estimate of approximately 200 kg ha(-1). Truncated models perform better
      on a P scale than on a D scale. The use of phenological stages improved yield
      assessment, particularly for those years with extreme meteorological conditions.
      The optimum models were tested and root-mean-square errors (RMSE) of 440 kg ha(
      1) and 470 kg ha(-1) were obtained for P and D scales respectively.

PMID- 14968355
TI  - Herbivore effects on developmental instability and fecundity of holm oaks.
AB  - Plants are able to compensate for loss of tissue due to herbivores at a variety
      of spatial and temporal scales, masking detrimental effects of herbivory on plant
      fitness at these scales. The stressing effect of herbivory could also produce
      instability in the development of plant modules, and measures of such instability
      may reflect the fitness consequences of herbivory if instability is related to
      components of plant fitness. We analyse the relationships between herbivory,
      developmental instability and production of female flowers and fruits of holm oak
      Quercus ilex trees by means of herbivore removal experiments. Removal of leaf
      herbivores reduced herbivory rates at the tree level, but had no effect on mean
      production of female flowers or mature fruits, whereas herbivory tended to
      enhance flower production and had no effect on fruit abortion at the shoot level.
      Differences in herbivory levels between shoots of the same branch did not affect
      the size and fluctuating asymmetry of intact leaves. These results indicate
      compensation for herbivory at the tree level and over-compensation at the shoot
      level in terms of allocation of resources to female flower production. Removal of
      insect herbivores produced an increase in the mean developmental instability of
      leaves at the tree level in the year following the insecticide treatment, and
      there was a direct relationship between herbivory rates in the current year and
      leaf fluctuating asymmetry the following year irrespective of herbivore removal
      treatment. Finally, the production of pistillate flowers and fruits by trees was
      inversely related to the mean fluctuating asymmetry of leaves growing the same
      year. Leaf fluctuating asymmetry was thus an estimator of the stressing effects
      of herbivory on adult trees, an effect that was delayed to the following year. As
      leaf fluctuating asymmetry was also related to tree fecundity, asymmetry levels
      provided a sensitive measure of plant performance under conditions of
      compensatory responses to herbivory.

PMID- 14968356
TI  - Density-dependent effects of multiple predators sharing a common prey in an
      endophytic habitat.
AB  - Multiple predator species feeding on a common prey can lead to higher or lower
      predation than would be expected by simply combining their individual effects.
      Such emergent multiple predator effects may be especially prevalent if predators
      share feeding habitat. Despite the prevalence of endophagous insects, no studies
      have examined how multiple predators sharing an endophytic habitat affect prey or
      predator reproduction. We investigated density-dependent predation of Thanasimus
      dubius (Coleoptera: Cleridae) and Platysoma cylindrica (Coleoptera: Histeridae)
      on a bark beetle prey, Ips pini (Coleoptera: Scolytidae), in a laboratory assay.
      I. pini utilize aggregation pheromones to group-colonize and reproduce within the
      stems of conifers. T. dubius and P. cylindrica exploit these aggregation
      pheromones to arrive simultaneously with the herbivore. Adult T. dubius prey
      exophytically, while P. cylindrica adults enter and prey within the bark beetle
      galleries. Larvae of both predators prey endophytically. We used a multiple
      regression analysis, which avoids confounding predator composition with density,
      to examine the effects of varying predator densities alone and in combination on
      herbivore establishment, herbivore reproduction, and predator reproduction.
      Predators reduced colonization success by both sexes, and decreased I. pini
      reproduction on a per male and per female basis. The combined effects of these
      predators did not enhance or reduce prey establishment or reproduction in
      unexpected manners, and these predators were entirely substitutable. The
      herbivore's net replacement rate was never reduced significantly below one at
      prey and predator densities emulating field conditions. Similar numbers of each
      predator species emerged from the logs, but predator reproduction suffered from
      high intraspecific interference. The net replacement rate of P. cylindrica was
      not affected by conspecifics or T. dubius. In contrast, the net replacement rate
      of T. dubius decreased with the presence of conspecifics or P. cylindrica.
      Combinations of both predators led to an emergent effect, a slightly increased
      net replacement rate of T. dubius. This may have been due to predation by larval
      T. dubius on pupal P. cylindrica, as P. cylindrica develops more rapidly than T.
      dubius within this shared habitat.

PMID- 14968357
TI  - Connexin expression and gap-junction-mediated cell interactions in an in vitro
      model of haemopoietic stroma.
AB  - In addition to the steady-state production of all blood cells, bone marrow can
      respond to an increased requirement for one or several cell lineages. The
      hormonal controls involved may act directly on blood cell progenitors or
      indirectly through modification of the haemopoietic environment. Intercellular
      gap junctions formed by connexins (Cx) provide direct communication among
      adjacent cells and the functional integration of multicellular systems. Since
      haemopoietic stroma is determinant for blood cell production, we have questioned
      whether gap-junction-dependent controls of haemopoiesis are sensitive to hormones
      and vitamins. We have analysed the expression, synthesis, cell distribution and
      formation of functional gap junctions in the murine bone-marrow stroma cell line
      S-17, and between stromal cells and blood cell progenitors. Nine Cxs were
      identified by reverse transcription/polymerase chain reaction, and only Cx43 by
      Western blot and immunofluorescence. All of the studied parameters were sensitive
      to intrinsic controls dependent upon the pattern of cell growth and modulated by
      exogenous controls mediated by retinol and steroids. Positive or negative
      modulation was specific for different Cxs. FACS analysis showed communication
      among the stromal cells and between stromal cells and myeloid (Mac1+) but not
      lymphoid (B220+) progenitors. Calcein transfer modulation did not correspond to
      the modulation of Cx43 expression and formation of connexons, suggesting the
      participation of other Cxs. Thus, functional gap junctions among haemopoietic
      stroma cells and between stroma and haematopoietic cells in the bone marrow may
      be modulated in response to hormonal stimuli, potentially controlling overall
      blood cell production.

PMID- 14968358
TI  - Neuroanatomical evidence for indirect connections between the medial preoptic
      nucleus and the song control system: possible neural substrates for sexually
      motivated song.
AB  - In European starlings ( Sturnus vulgaris) as in other seasonally breeding
      songbirds, a major function of song during the breeding season is mate
      attraction, and song in this context is highly sexually motivated. Song learning,
      perception, and production are regulated by nuclei of the song control system,
      but there is no evidence that these nuclei participate in the motivation to sing.
      Evidence suggests that the medial preoptic nucleus (POM), a diencephalic nucleus
      outside of the song control system, might regulate the motivation to sing, at
      least in a sexual context. If the POM is involved in the regulation of sexually
      motivated song, then this structure must interact with the song control system.
      To examine possible neuroanatomical connections between the POM and song control
      nuclei a tract-tracing study was performed in male starlings using the antero-
      and retrograde tract tracer, biotinylated dextran amine (BDA). No direct
      connections were identified between the POM and song control nuclei; however,
      labeled fibers were found to terminate in a region bordering dorsal-medial
      portions of the robust nucleus of the archistriatum (RA). Additionally, several
      indirect routes via which the POM might communicate with the song control system
      were identified. Specifically, POM projected to dorsomedial nucleus
      intercollicularis (DM), mesencephalic central gray (GCt), area ventralis of Tsai
      (AVT), and locus ceruleus (LoC), structures projecting directly to nuclei
      involved in song production (DM --> vocal-patterning and respiratory nuclei; GCt,
      AVT, LoC --> RA and HVC, and the context in which song is sung (AVT --> area X).
      These results are consistent with the possibility that the POM regulates sexually
      motivated song through interactions with brain regions involved in vocal
      production.

PMID- 14968359
TI  - A gradient of TFF3 (trefoil factor family 3) peptide synthesis within the normal
      human gastric mucosa.
AB  - TFF3 is a member of the trefoil factor family (TFF) peptides, which enhance the
      surface integrity of mucous epithelia, and is typically secreted by intestinal
      goblet cells together with the mucin MUC2. Reports of the expression of TFF3
      within the normal human stomach are contradictory and the precise localisation of
      TFF3 is unknown. We have mapped the human gastric mucosa by reverse
      transcription/polymerase chain reaction and Western blot analysis and by
      immunohistochemistry. Small amounts of TFF3 were detectable in the oxyntic mucosa
      of the corpus, whereas TFF3 synthesis increased sharply distal to the corpus
      antrum transitional zone. TFF3 secretion was demonstrated in the antrum, the
      pyloric region and the proximal duodenum. High TFF1 levels were present in all
      regions of the gastric mucosa including the corpus, whereas the proximal duodenum
      was nearly devoid of TFF1. Immunohistochemistry localised TFF3 to antral and
      pyloric surface mucous cells. In the antrum, an increasing concentration gradient
      was found towards cells deeper in the isthmus. TFF1 was confined to superficial
      pit cells in the antrum. TFF3 was also present in specific layers of the
      laminated mucous gel of the antral and pyloric regions and variable
      concentrations of TFF3 (2-62 nmol/l) were measured in gastric juice. Here, a
      probably N-terminally shortened variant is present that forms disulphide-linked
      dimers. Thus, TFF3 is a typical secretory peptide of the normal human antral and
      pyloric gastric mucosa and has a gastric expression pattern different from that
      of TFF1 and TFF2. TFF3 might therefore have important physiological functions in
      the stomach, e.g. as a luminal surveillance peptide maintaining particularly the
      integrity of the antral and pyloric mucosa.

PMID- 14968360
TI  - New genomic region for Wegener's granulomatosis as revealed by an extended
      association screen with 202 apoptosis-related genes.
AB  - Wegener's granulomatosis (WG) is a systemic disease with complex genetic
      background. It is characterized by necrotizing granulomatous inflammation of the
      upper and lower respiratory tract, glomerulonephritis, vasculitis and the
      presence of antineutrophil cytoplasmatic autoantibodies (C-ANCAs) in sera of
      patients. Here, we report on an extended association screen (EAS) with 202
      microsatellite markers, representing apoptosis-related genes and further genes
      down-regulated in apoptotic neutrophils, using pooled DNA of 150 Northern German
      patients suffering from WG and 100 healthy Northern German controls. Six
      microsatellite allele patterns were found significantly associated with WG, three
      of which could be confirmed by individual genotyping. One marker remained
      significantly associated after multiple corrections. This marker representing the
      retinoid X receptor beta gene (RXRB, P=7.60x10(-6), distance to gene:
      approximately 5.3 kb) is localised in the major histocompatibility complex (MHC)
      region between the HLA-DPB1 and DAXX genes. HLA-DPB1 typing and fine mapping of
      the region with additional microsatellites and single-nucleotide polymorphisms
      (SNPs) revealed a strong association of WG with the significantly over
      represented DPB1*0401 ( P=1.51x10(-10), OR=3.91) allele compared with the control
      cohort. In addition, an extended haplotype DPB1*0401/RXRB03 was identified
      showing an even stronger association with WG ( P=7.13x10(-17), OR=6.41). These
      results represent the strongest association of a genomic region with WG,
      suggesting a major genetic contribution in the aetiology of the disease. Thus,
      our data demonstrate that EAS may be a valuable alternative approach for
      determining genetic predisposition factors in multifactorial diseases.

PMID- 14968361
TI  - Maternal administration of high dose vitamin D3 for cerebral palsy in her child.

PMID- 14968362
TI  - Expression of thymosin beta4 during chick development.
AB  - We cloned the chick homologue of Homo sapiens thymosin beta4, encoding a G-actin
      sequestering factor which plays an important role in angiogenesis, cell motility
      and tumorigenesis. The thymosin beta4 gene is highly conserved between chick and
      human. Its expression was analyzed during different stages of development. At
      early stages thymosin beta4 is expressed in the mesoderm and endoderm and in
      Hensen's node. Later, thymosin beta4 transcripts are found in the head
      mesenchyme, somites, dorsal root ganglia, neural tube, brain, blood vessels and
      feather buds. The pattern of thymosin beta4 expression in blood vessels indicates
      a function mainly in development of the blood circulatory system which closely
      parallels findings in vitro. The observed expression pattern shows a high
      similarity to expression data published for mice, mainly in the heart and in the
      nervous system. Important new aspects are the early onset of expression, the
      expression in the mesoderm preceding heart formation and the involvement in
      feather development.

PMID- 14968363
TI  - Cell cycle and no end.
AB  - Our knowledge about the molecular circuits regulating the duplication of the
      genetic material and the subsequent division of a cell into two daughter cells
      has exploded over the last decade. Aberrations in the regulation of the cell
      cycle belong to the hallmarks of malignant transformation, leading, in turn, to
      the development of tumours. After introducing the basics of eukaryotic cell-cycle
      regulation and describing the four phases of the cell cycle (namely, G1, S, G2
      and M) in more detail, alterations of key components of the cell-cycle machinery
      in human malignancies and their functional consequences are presented.
      Principally, deregulation of the cell cycle can be caused by unrestricted
      activity of cell-cycle promoting factors (many oncogenes fall into this class) or
      by inactivation of inhibitory factors (many tumour suppressor genes belong to
      this class). Both types of deregulation have been described in human tumours and
      are discussed in detail. Perspectives concerning the translation of this
      knowledge into daily routine practice and future applications are discussed at
      the end. The molecular mechanisms of actual cell division (sister chromatid
      segregation and cytokinesis) are mentioned only briefly.

PMID- 14968364
TI  - Accessory spleens: preoperative diagnostics limitations and operational strategy
      in laparoscopic approach to splenectomy in idiopathic thrombocytopenic purpura
      patients.
AB  - AIM: The preoperative detection of accessory spleen (AS) is still a very
      important and serious problem. The aim of the study was to assess the reasons for
      failure and the long-term results of laparoscopic splenectomy (LS) in patients
      with idiopathic thrombocytopenic purpura (ITP). METHOD: Fifty-eight ITP patients
      underwent LS between June 1998 and December 2002. There were 42 women and 16 men.
      Preoperatively, we performed computed tomography (CT) and sonography to evaluate
      the size of the spleen and possibly to recognize the presence of the accessory
      spleens, which were found preoperatively in three cases. RESULTS:
      Intraoperatively, ASs were found in the course of laparoscopy in six cases
      overall, three preoperatively false negative. During follow-up (median time 31
      months), in three patients the low platelet count was recognized, respectively
      after 5 months and 1.5 and 1.8 years. In all those cases scintigraphy was
      performed and in one case the residual accessory spleen, missed both in
      preoperative examination and during laparoscopy, was revealed. In two other
      patients, in spite of thrombocytopenia, no residual spleens were found.
      CONCLUSION: We conclude that the problem of accessory spleens can be managed by
      careful videoscopic examination of the abdominal cavity during splenectomy, while
      the use of preoperative imaging techniques in detection of accessory spleens is
      still limited by the insufficient sensitivity of the examination.

PMID- 14968365
TI  - Morphological changes in the optic disc after vitrectomy and fluid-air exchange.
AB  - BACKGROUND: Although many investigators have previously reported various ocular
      complications induced by vitrectomy, little is known about post-operative
      morphological changes in the optic disc. The purpose of this study is to evaluate
      the effect of vitrectomy and fluid-air (F-A) exchange on the post-operative
      morphology of the optic disc. METHODS: We examined 31 eyes that had undergone
      vitrectomy for macular holes (22 eyes) or epiretinal membranes (9 eyes). Only the
      patients with macular holes were treated by fluid-air exchange. Morphological
      changes in the optic disc were evaluated using the Heidelberg Retina Tomograph.
      RESULTS: C/D area ratios significantly decreased for 6 months post-operatively.
      The rim volumes significantly increased for 1 month following surgery. Cup
      volumes significantly decreased at 3 months after surgery. No significant change
      of mean cup depth was observed post-operatively. The eyes that had not been
      subjected to F-A exchange showed no significant morphological change following
      surgery. In contrast, the eyes that had undergone F-A exchange showed significant
      decrease in C/D area ratio and cup volume and an increase in rim volume and mean
      cup depth for considerable periods following surgery. Any of the patients showed
      no post-operative visual field loss. CONCLUSION: Whereas no visual field loss is
      observed, vitrectomy with F-A exchange induces morphological changes in the optic
      disc for significant periods following surgery.

PMID- 14968367
TI  - Spinal mobility: sagittal range of motion measured with the SpinalMouse, a new
      non-invasive device.
AB  - INTRODUCTION: In this paper the SpinalMouse, a new computerised external device
      for measuring sagittal spinal range of motion (ROM), was tested for inter-rater
      reliability and use in clinical practice. MATERIALS AND METHODS: To assess inter
      rater reliability, two investigators each measured 111 subjects. RESULTS:
      Correlation coefficients were found to be r=0.90 for flexion, r=0.85 for
      extension and r=0.90 for total inclination. Intra-class coefficients were 0.95
      for flexion, 0.92 for extension and 0.95 for total inclination. A poor agreement
      (kappa=0.22) was found for the presence of outliers from normal values for
      intersegmental ROM. CONCLUSION: We conclude the device is a useful, reliable tool
      for measuring sagittal spinal ROM in clinical practice, considering the small
      load it confers on patients and the short amount of time the measurement
      involves. The SpinalMouse might be more accurate after following the
      recommendations we make.

PMID- 14968366
TI  - Alefacept therapy reduces the effector T-cell population in lesional psoriatic
      epidermis.
AB  - Alefacept, a LFA-3/IgG1 fusion protein, interferes with the activation and
      proliferation of T cells by binding to the CD2 receptor on their surfaces. The
      clinical efficacy of this drug has been demonstrated in chronic plaque psoriasis.
      We performed a single-center, open-label study to investigate the
      immunohistochemical effects in psoriatic lesional skin. A group of 11 patients
      with plaque psoriasis all received 12 weekly doses of 7.5 mg alefacept
      intravenously. Skin biopsies were obtained at baseline and on days 8, 43 and 92,
      and were evaluated by digital image analysis after immunohistochemical staining.
      After completion of treatment, 8 out of the 11 patients experienced a reduction
      in PASI of 50% or more compared to baseline. Immunohistochemical analysis
      displayed a gradual decrease in the number of cutaneous T cells during therapy,
      with a significant reduction in epidermal CD8+ cells and dermal CD4+ cells on day
      92. Patients with a reduction in PASI of 50% or more after therapy had a
      clearance of effector/memory T cells from the epidermis, in contrast to patients
      with a reduction in PASI of less than 50%. These findings support the hypothesis
      that effector/memory T cells play a prominent role in the pathogenesis of
      psoriasis, and that alefacept is capable of reducing these cells in lesional
      psoriatic skin.

PMID- 14968368
TI  - Neonatal spinal muscular atrophy with multiple contractures, bone fractures,
      respiratory insufficiency and 5q13 deletion.
AB  - We present the case of a floppy neonate with marked and generalized weakness,
      respiratory insufficiency and fetal akinesia deformation sequence. The infant
      showed multiple joint contractures, two bone fractures and needed mechanical
      ventilation from birth to death at 16 days of age. Electrophysiological
      assessment showed electrically unexcitable motor and sensory nerves. Muscle
      biopsy showed diffuse atrophy of type I and type II fibers. Necropsy confirmed
      the diagnosis of infantile spinal muscular atrophy (SMA) with severe loss of
      motor neurons in anterior horns and motor nuclei of brainstem. There were also
      neuronal loss, gliosis, chromatolysis, ballooned cells, empty cell beds and
      neuronophagia figures in other brainstem and brain nuclei. Genetic analysis of
      the patient revealed homozygous deletions of survival motor neuron gene 1 (SMN1)
      and a single copy of SMN2 in region 5q13. This case confirms that the loss of
      spinal motor neurons underlies the muscular atrophy in severe cases of 5q SMA.
      This case also shows that the presence of multiple joint contractures, bone
      fractures and respiratory insufficiency in SMA in the neonatal period does not
      necessarily exclude the occurrence of classical deletions in the SMA 5q13 region.
      Rather, these atypical clinical findings show the extreme severity and prenatal
      onset of the disease in these SMA cases, which may be related with the occurrence
      of a single copy of SMN2 gene. More reports of clinically, pathologically and
      genetically well-documented cases are essential to define the different types of
      this disease.

PMID- 14968372
TI  - Frontobasilar fractures in children.
AB  - OBJECT: Forehead, anterior cranial base and orbito-naso-ethmoidal fractures,
      combined with brain injuries and dural tears, constitute a frequent pattern of
      injury in infants and children less than 5 years of age when major anterior
      craniofacial trauma occurs. Fractures of the orbital roof, despite the common
      blow-out floor fractures, are considered uncommon events. In children younger
      than 7 years this pattern of fracture may be a consequence of nonpneumatized
      frontal sinuses. METHODS: Complete assessment using CT scans combined with
      neurosurgical, ophthalmological, anesthesiological and craniofacial
      reconstructive evaluations are necessary to repair the injured dura and
      craniofacial skeleton. The coronal approach provides the best exposure of the
      fractured regions to the surrounding regular structures. CT scans are useful in
      defining the extent and the pattern of the fractures. Once the brain and dura
      injuries have been managed by the neurosurgeon, the anterior cranial base must be
      reconstructed by applying the basic craniofacial principles, reduction and
      stabilization of fractures, sealing off the anterior cranial base. We present
      four cases of frontobasilar fractures in children, two of which involved the
      orbital roof. CONCLUSIONS: The treatment of pediatric maxillofacial traumas,
      therefore, requires consideration of different factors from those in adults, and
      a different therapeutic approach: respect of the functional matrix (growth
      principle) and employment of the least invasive surgical approach. Fixation that
      adequately stabilizes the facial skeleton is also required. The need to provide
      rigid bony fixation in the surgical treatment of craniofacial disorders in
      children without impacting the growth has inspired the evolution of operative
      techniques and fixation devices, with the development of reabsorbable bone
      fixation. When bony defects are present or reconstruction of the complete orbital
      roof and anterior cranial base is required, autogenous cranial bone is used.

PMID- 14968373
TI  - Can CT predict the level of CSF block in tuberculous hydrocephalus?
AB  - INTRODUCTION: Treatment of obstructive hydrocephalus in children with tuberculous
      meningitis (TBM) depends on the level of the cerebrospinal fluid (CSF) block. Air
      encephalography is regarded as the gold standard for differentiating
      communicating and non-communicating hydrocephalus. Since air-encephalography
      involves a lumbar puncture, it carries the risk of cerebral herniation. AIM. The
      aim of this study was to determine whether communicating and non-communicating
      hydrocephalus in TBM can be differentiated by means of cranial computerised
      tomography (CT). METHODS: A number of CT indices were measured in 50 children
      with communicating and 34 children with non-communicating hydrocephalus according
      to air-encephalographic findings. RESULTS: The only CT finding that correlated
      with the type of hydrocephalus was the shape of the third ventricle.
      Significantly more children with non-communicating hydrocephalus had a rounded
      third ventricle than those with communicating hydrocephalus. CONCLUSION: CT is
      therefore not useful in determining the level of CSF block in TBM. Air
      encephalography remains the most reliable way of determining the level of CSF
      obstruction.

PMID- 14968374
TI  - Lymphokine activated killer cells from umbilical cord blood show higher antitumor
      effect against anaplastic astrocytoma cell line (U87) and medulloblastoma cell
      line (TE671) than lymphokine activated killer cells from peripheral blood.
AB  - OBJECTS: The aims of this study were to assess the cytotoxic capability of
      lymphokine-activated killer (LAK) cells from umbilical cord blood (UCB), to
      compare them with those of peripheral blood (PB)-derived cells against anaplastic
      astrocytoma cell line (U87) and medulloblastoma cell line (TE671), and to
      identify which mechanism and genes were involved in cytotoxicity. METHODS: The
      effector cells were generated by interleukin-2 from UCB and PB. The antitumor
      property of effector cells against the target cells (U87, TE671) were estimated
      using a visual survival cell assay. The mixed target and effector (UCB) cells
      were analyzed for whether DNA fragmentation was present or not. Reverse
      transcription polymerase chain reaction analysis was then performed to estimate
      the statement of the perforin and FasL genes in activated and inactivated cells
      from UCB. RESULTS: The higher in vitro antitumor properties of the LAK cells from
      UCB were observed in comparison to the LAK cells from PB against the U87 and the
      TE671 ( p<0.05). Apoptosis may be one of the lysis mechanisms of target cells by
      the LAK cells from UCB. The contributing genes could be FasL and perforin.
      CONCLUSIONS: This study suggests that UCB may be used as a source of LAK cells in
      adults and children suffering from anaplastic astrocytoma or medulloblastoma.

PMID- 14968380
TI  - [Radiological analysis of the thrust plate prosthesis (TPP)].
AB  - AIM: The various radiological changes after implantation of the thrust plate
      prosthesis (TPP) are demonstrated and, with the help of a standardized
      radiological classification, divided in pathological and non-pathological
      findings. METHOD: The radiological follow-ups of 167 TPP implanted between 1993
      and 1998 was analyzed in this study. The follow-up examination was carried out
      postoperatively, after 6 months and subsequently every year. The radiological
      assessment was carried out in an exact a.p. view. We subdivided the images into
      four sectors: A corresponds to the femoral neck stump, B to the bony stock
      cranial (=1) and caudal (=2) to the mandrel of the prosthesis, C is the region
      above and under the bolt and D the cortical area around the lateral plate.
      RESULTS: Radiolucencies were especially seen in sector A (A 1 = 34.7 %; A 2 =
      18%) and sector C (44 %). As a pathological finding, we saw progressive
      radiolucencies of sector B (6 %), which were interpreted to be a sign of
      loosening, when they showed a thickness of = 2 mm. Furthermore, in some cases we
      observed extended atrophy under the lateral plate, which was also judged to be a
      sign of loosening. CONCLUSION: The radiological changes of the bony stock of the
      TPP can be divided into physiological adaptation processes because of changed
      biomechanics and signs of loosening. As a stress-shielding phenomenon we see a
      progressive atrophy under the thrust plate and simultaneously a sclerosis of the
      spongious bone above the calcar femoris. An indication for a loosening of the
      prosthesis is a progressive radiolucency of sector B.

PMID- 14968381
TI  - [Midterm results and revisions of the thrust plate prosthesis (TPP)].
AB  - AIM: Although already in use for 20 years, the concept of the metaphyseal
      anchored thrust plate prosthesis has not yet gained general acceptance. Clinical
      and radiological follow-up examinations were carried out 5 to 8 years after
      implantation of a TPP. We tried to answer the question if the metaphyseal
      anchorage of the cement-less TPP is equal to a diaphyseal anchorage of a cement
      less stem prosthesis and to define the advantages of the TPP. METHODS: We
      included 170 of the patients from our clinic with an implanted TPP in this study.
      Furthermore we reviewed the results of 30 revision hip arthroplasties of the TPP.
      The clinical examination were carried out using the Harris hip score while the
      radiological examinations were performed on the basis of predefined criteria.
      RESULTS: We found good clinical results. The preoperative Harris score of 48.7
      increased to 93.7 at 24 months postoperatively. Radiolucencies were detected and
      were of varying relevance in dependence on their localization. The Kaplan-Meier
      survival analysis at 8 years was 90.5 %. The clinical results after changing the
      TPP were also good to excellent. The mean Harris hip score was 87.3. CONCLUSION:
      Our study suggests that in spite of a slightly higher aseptic loosening rate in
      comparison to the cement-less stem prosthesis, the thrust plate prosthesis proved
      to be worthwhile. On the basis of previous experience we assume that the TPP is a
      good alternative implant especially for young patients.

PMID- 14968382
TI  - [Analysis of validity and reliability of three radiographic classification
      systems for preoperative assessment of bone stock loss in revision total hip
      arthroplasty].
AB  - AIM: It was the purpose of this prospective study to analyze validity and
      reliability of three different radiographic classification systems, which are
      used to assess bone stock loss prior to revision total hip arthroplasty. METHOD:
      Investigation was performed using the classification systems according to 1)
      Paprosky et al., 2) Hungerford et al., and 3) the German Society of Orthopaedics
      and Traumatology (DGOT). Twenty-eight consecutive patients with diagnosis of
      aseptic failure of total hip arthroplasty were enrolled in the study. Interrater
      agreement was analyzed by evaluating the classifications preoperatively by three
      investigators with different level of clinical experience using a blinded
      observer technique. Validity was analyzed by comparison of preoperative
      radiographic findings (n = 3) and an intraoperative control by visualization and
      palpation (n = 1). Spearman coefficient of correlation (r(s)) was used to
      establish levels of agreement among multiple ordinal variables. RESULTS:
      Interrater reliability testing using paired comparison between the three
      investigators revealed non-homogeneous coefficients of correlation (r(s):
      Paprosky femur: 0.45 - 0.67, acetabulum: 0.38 - 0.63; Hungerford: 0.46 - 0.66;
      DGOT femur: 0.38 - 0.59, acetabulum: 0.42 - 0.76). Paired analysis of correlation
      between preoperative and intraoperative findings again showed non-homogeneous
      coefficients of correlation (r(s): Paprosky femur: 0.59 - 0.68, acetabulum: 0.39 
      0.70; Hungerford: 0.39 - 0.74; DGOT femur: 0.44 - 0.60, acetabulum: 0.36 -
      0.76). In general, defects were grossly underestimated preoperatively. The level
      of experience did not influence the validity of measurements. CONCLUSION: Our
      results indicate that these classifications do not provide valid and reliable
      assessment of femoral and acetabular bone stock loss prior to revision total hip
      arthroplasty.

PMID- 14968383
TI  - [Early postoperative functional differences between total knee arthroplasties
      supplied with mobile-bearing platform or fixed-bearing system--an analysis of
      gait pattern].
AB  - AIM: The goal of this study was to analyze differences of gait patterns among
      patients with total knee arthroplasty supplied with mobile-bearing platform in
      contrast to patients supplied with fixed-bearing knee systems. METHOD: For that
      reason 17 patients with mobile-bearing knee systems and two groups of 15 patients
      each with fixed-bearing knee systems have been examined clinically,
      radiologically, and by means of gait analysis up to 6 months postoperatively.
      Additionally 20 knee-healthy control subjects have been gait-analyzed for
      comparison. RESULTS: There existed no different developments of gait
      characteristics between the groups of patients in the preoperative status. After
      the operation an increase of the ground reaction force of the operated leg was
      observed in all groups. The functional range of motion in the operated knee joint
      improved among patients postoperatively. Besides, in the group with the mobile
      bearing knee a significantly stronger flection of the operated leg during the
      stance phase under load could be proven. Between the groups of patients the
      average values of the respective radiological alignments did not exhibit
      statistically significant differences. No severe complications have been
      observed. CONCLUSION: For the group of patients with fixed-bearing knee course
      samples have been registered, which approximate the reference values of healthy
      control subjects more strongly. The entire course sample is characterized by an
      increased range of motion of the opposite side and the adjacent joints. The
      parameters measurable in the gait analysis point to a better biomechanical
      situation after implantation of the mobile-bearing system.

PMID- 14968384
TI  - [Relevance of wound drainage in total knee arthroplasty--a prospective
      comparative study].
AB  - AIM: The benefits of postoperative wound drainage in patients with total knee
      arthroplasty (TKA) with regards to mobilisation and wound healing were studied.
      We wanted to determine the efficacy of an autologous blood retransfusion system.
      METHOD: 150 patients with TKA were divided into three groups of 50 patients: A)
      three wound drainages with an autotransfusion system and suction; B) no wound
      drainage; C) one intraarticular wound drainage without suction. Hemoglobin
      values, blood transfusion requirements, blood loss, postoperative range of
      motion, Insall knee score and rate of complications were observed and recorded.
      All patients were operated without tourniquets for lower blood loss. RESULTS: In
      the group of patients with wound drainage and a retransfusion system the
      requirement of postoperative additional blood transfusion was not significantly
      less than in the group without wound drainage. Group A had the highest blood loss
      of all. The group without wound drainage had more hematomas and wound healing
      complications. Best results were observed within the group with one
      intraarticular drainage without suction. The rate of complications was not
      increased and the blood transfusion requirements were the lowest. CONCLUSION:
      This study shows that total knee replacement involving one intraarticular wound
      drainage without suction attains the best results.

PMID- 14968385
TI  - [Computer-assisted periacetabular triple osteotomy for treatment of dysplasia of
      the hip].
AB  - AIM: Besides general risks, reorienting periacetabular osteotomies include the
      risks of over- or under-correction. Therefore, intraoperative computer-assisted
      control of the pelvic fragment may allow for precise reorientation of the
      acetabulum in all planes. METHODS: The advantages and problems of a computer
      assisted periacetabular osteotomy are demonstrated in a 19 year old female with
      spastic paresis and severe secondary dysplasia of the hip over a postoperative
      follow up period of 2 years. Because of progressive subluxation of the left
      femoral head with initial degenerative changes of the hip joint a pelvic triple
      osteotomy as described by Tonnis and an intertrochanteric derotation-varus
      osteotomy were performed. The intraoperative control of the acetabular position
      was optimized by CT based navigation. To compare and evaluate the pre- and
      postoperative clinical and functional outcome, X-rays, CT scans and a gait
      analysis were applied. RESULTS: The computer assisted orthopedic surgery (CAOS)
      technique allows for precise intraoperative control following reorientation of
      the acetabular fragment in all three planes. The pre- and postoperative clinical
      and radiological findings were compared and the result was classified as good.
      CONCLUSION: Although the costs and logistics for pelvic osteotomies are increased
      by CAOS technology, the authors favor this technique for corrective surgery of
      complex acetabular deformities, although individual parameters need to be
      considered in each patient.

PMID- 14968386
TI  - [Arthroscopic joint debridement for gonarthrosis: influence of degree of chondral
      damage and muscle weakness on results].
AB  - AIM: Purpose of this study was to investigate the correlation between subjective
      patient discomfort, chondral damage and muscular weakness in cases of
      gonarthrosis (OA). METHODS: In 22 patients suffering from OA who underwent
      arthroscopy, the complaints were scored by the Lysholm score. Chondral damage was
      determined by a special "chondral score". The maximum peak torque was measured
      pre- and postoperatively (isokinetic test, Cybex 6000 dynamometer). RESULTS:
      Joint debridement and subsequent postoperative aggressive rehabilitation produced
      a significant increase in the Lysholm score (from 45.7 to 77.5 points).
      Subjective complaints correlated significantly with the degree of chondral
      damage. After treatment, the strength of the extensor muscles increased
      significantly. The strength of the flexor muscles strength also increased
      tendentially. However, there was a deficit in muscular strength in comparison to
      the contralateral leg in all cases. The subjective complaints correlated with the
      loss of muscle strength at slow angular velocities. CONCLUSIONS: The patients"
      evaluation with the Lysholm score in combination with an arthroscopic chondral
      score and the measurement of the isokinetic muscle strength is a suitable method
      to obtain information about the chances of success for arthroscopic joint
      debridement in patients suffering from OA. Arthroscopic treatment is an
      appropriate measure for a short-term reduction of subjective complaints in OA.
      But it is also useful to reduce muscular deficits.

PMID- 14968387
TI  - [Preliminary results after multiple knee injuries with operative reconstruction
      of chronic posterior-lateral instabilities].
AB  - AIM: The operative treatment of posterior knee instability is a difficult problem
      and the literature does not offer methods as good as ACL reconstruction. METHODS:
      With a new operative approach the authors have attempted to improve the surgical
      procedure and the final outcome in terms of stability and function. To illustrate
      our clinical findings, 20 cases of chronic posterior-lateral knee instability
      were retrospectively reviewed following PCL reconstruction. We examined 5 women
      and 15 men. The average follow-up period was 14 months (6 - 24 months) and the
      average age was 30 (17 - 59) years. RESULTS: Subjectively all patients were
      satisfied with the surgical outcome and there were no intraoperative technical
      difficulties and no patient had a postoperative problem. The p.-a. instability
      measured at 20 degrees of knee flexion was preoperatively 11.7 mm,
      postoperatively 7.2 mm and 6.7 mm on the uninjured side. The Lysholm score was
      preoperatively 59 (35 - 71) points and postoperatively 85 (65 - 100) points. 19
      patients returned to work and 14 patients were able to participate in sports.
      CONCLUSION: The results demonstrate that the knee still does not have a normal
      stability postoperatively, but the results were reproducible and the method
      appears to be reliable.

PMID- 14968388
TI  - [First results of anterior versus posterior instrumentation-fusion in the
      treatment of spondylodiscitis].
AB  - AIM: The present study on spondylodiscitis patients was carried out to compare
      prospectively and randomized the results of clinical and radiological outcomes of
      anterior versus posterior instrumentation after debridement and grafting. We
      aimed to make a recommendation concerning the optimum treatment of
      spondylodiscitis. METHOD: A total of 22 patients with spondylodiscitis were
      enrolled in the randomized trial to undergo an operation with anterior or
      posterior instrumentation after debridement and fusion with autologous bone
      transplant. 12 patients (group 1) were assigned to posterior Universal Spine
      System stabilization. 10 patients (group 2) were treated with anterior VentroFix
      instrumentation. In a prospective clinical investigation we have examined both
      operative therapies with regard to clinical and radiological outcome. The follow
      up was one year. RESULTS: In patients with ventral Spondylodesis (group 2), prior
      recreation of patients was achieved in clinical examination and blood tests.
      Radiological results are even equivalent in both groups. Therefore we recommend
      ventral instrumentation as the superior surgical procedure. But the individual
      local situation has to enable ventral stabilization. CONCLUSION: We found
      advantages with anterior instrumentation in comparison to posterior stabilization
      in patients with spondylodiscitis. Advantages of ventral stabilization cause
      early mobilization postoperatively without any increase in complication rates.
      Except for operation time and intraoperative blood loss, no statistical
      difference were was seen. Important is the individual indication for each method
      depending on anatomical and clinical signs. Ventral instrumentation should be
      restricted to cases with sufficient bone stock.

PMID- 14968389
TI  - [Extensive spinal epidural hematoma--an uncommon entity following cervical
      chiropractic manipulation].
AB  - INTRODUCTION: Spinal epidural hematoma is a rare complication after chiropractic
      manipulation. In the literature, only three cases have been reported, which all
      necessitated surgical treatment. CASE: A 27-year-old woman was treated with
      cervical chiropractic manipulation (C5/6) and facet joint infiltration. 10
      minutes later the patient presented signs of intracranial pressure with nausea,
      vertigo, headache and vomiting. The magnetic resonance imaging of the spine
      demonstrated an epidural hematoma extending from the cervical to the sacral
      spine. As the patient had no sensible or motor deficits and recovered quickly,
      surgical treatment was not necessary. A few days later the patient had a complete
      persisting remission of symptoms. CONCLUSION: If neurological deficits occur
      after chiropractic manipulation, a spinal epidural hematoma should be considered
      to provide adequate therapy without delay. The current case report shows an
      unusual expansion of the hematoma which has not described so far after
      chiropractic manipulation. But, in contrast to the three cases reported before, a
      surgical intervention was not necessary.

PMID- 14968390
TI  - [Occurrence of a segmental kyphosis after laminectomy of C2 for an aneurysmatic
      bone cysts--course and treatment strategy].
AB  - HISTORY: A 9-year-old girl suffered from an enlarging tumor in the lamina of the
      axis. After resection of the aneurysmatic bone cyst via laminectomy of C2 an
      anterior plate-fusion of C2/3 was done. Instead of a correctly placed ventral
      cervical plate, an adjacent instability of the level C3/4 with kyphosis and
      subluxation of the facet joints was seen at follow-up. COURSE OF TREATMENT: After
      reposition over a hypomochlion retention was achieved with a halo body-jacket.
      Two weeks later the level C3/4 was stabilized by posterior instrumentation. After
      almost two years the patient has no complaints and the radiological controls show
      correctly placed instrumentation and increasing bony fusion at the levels C2/3
      and C3/4. CONCLUSION: Especially in children and adolescents laminectomy of a
      cervical vertebra often leads to kyphotic deformities. When using a posterior
      approach for surgery of intraspinal lesions or in case of tumors of the dorsal
      elements of the spine, the laminae and posterior structures should be preserved
      or, respectively, reconstructed for restoration of traction and tension
      mechanisms. This is of essential relevance for biomechanical stability and
      maintenance of the sagittal profile of the spine.

PMID- 14968391
TI  - [Biomechanical testing of different ventral fixation devices on the bovine lumbar
      spine].
AB  - AIM: The primary stability of ventral fixation systems has been improved over the
      past years and special implants supporting minimally invasive procedures have
      been developed. The aim of this study was to analyze the primary stability of
      several of these implants. METHODS: Thirty (30) lumbar segments from 5 to 7-month
      old calves were harvested and tested on a pure moment apparatus (PMA) as well as
      a modified materials testing machine (MTS) according to the European standard
      recommendations of Wilke et al. Three different implant systems (MACS, Centaur
      and Z-plate) were included. ROM, neutral zone and stiffness were tested on the
      PMA up to 10 Nm, stiffness at an eccentric axial load of up to 1500 N was tested
      on the MTS. Bone density was investigated for all specimens. Statistical analysis
      was performed by ANOVA and LSD tests. RESULTS: Primary stability was improved by
      all fixation devices compared to the physiological specimen. The MACS implant was
      more stable than the Centaur and Z-plate with the exception of in lateral bending
      [where the Z-plate was stiffer]. Bone density was comparable in the three
      different experimental groups. CONCLUSION: Minimal invasive ventral fixation
      devices are becoming popular. The primary stability of the minimal invasive MACS
      was comparable to those of other well-known ventral fixation devices of the
      lumbar spine.

PMID- 14968392
TI  - [Posteromedial bowing of the lower leg and neuroblastoma with possible
      neurofibromatosis type I: a case report and literature review].
AB  - BACKGROUND: The posteromedial bowing of the tibia is a rare condition that is not
      yet known to be related to neurofibromatosis. The case of a three month-old boy
      with the tentative diagnosis of neurofibromatosis is described. He developed
      paraplegia due to an abdominal neuroblastoma at the age of 9 months. This led us
      to a review of the literature. METHOD: 122 cases of posteromedial bowing of the
      tibia in 20 publications of the years 1949 - 2000 were analysed under special
      respect to gender, side of affection, shortening of the lower leg, treatment and
      possible cause. RESULTS: The posteromedial bowing of the lower leg seems to
      affect more boys as well as the left side. As far as described in all but one
      case it was the first delivery. Regularly, a limb shortening and pes
      calcaneovalgus is to be found. 99 children were treated conservatively, 21 got an
      operation of the affected side. In 19 performed osteotomies no pseudarthrosis
      occurred. One case of a fracture due to an adequate trauma without healing
      problems is described.

PMID- 14968393
TI  - [Resorbable pin refixation of an osteochondral fracture of the lateral femoral
      condyle due to traumatic patellar dislocation: case management, follow-up and
      strategy in adolescents].
AB  - AIM: Intraarticular osteochondral fractures resulting from traumatic patellar
      dislocation in children are reported most frequently between 13 and 15 years of
      age. Fracture localization concerns, apart from loose intraarticular bodies, the
      inferiomedial patellar facet and the lateral femoral condyle. Osteochondral
      fractures of the lateral femoral condyle with more than 50 % of its surface are
      extremely rare and reported infrequently. METHOD: We report a traumatic patellar
      dislocation in a 14 year old patient that let to an osteochondral fracture of the
      lateral femoral condyle. MRI-scan demonstrated an extensive fracture size
      concerning more than 50 % of the condylar surface with intraarticular
      dislocation. Initially arthroscopic surgery followed an open reduction and
      internal refixation of the osteochondral fragment with resorbable, poly-p
      dioxanon pins. RESULTS: Follow-up MRI-scan revealed 7 weeks after surgery an
      adequate repositioning of the fragment with correct pin placement. Second-look
      arthroscopy demonstrated an osteochondral reintegration of the fragment within a
      period of 7 months after prior surgery. CONCLUSION: Resorbable poly-p-dioxanon
      pins as a mean for refixation of an osteochondral, intraarticular fracture in an
      adolescent, with an arthroscopic confirmed acceptable result, seem to be a
      considerable therapy option.

PMID- 14968394
TI  - [Rational use of blood cell products in orthopedics and traumatology].
AB  - STUDY DESIGN: The risk of transmission of human immunodeficiency virus (HIV),
      hepatitis B and C viruses as well as the development of costs has changed the use
      of homologous blood cell products. METHODS: The present investigation shows the
      state of the art of blood salvage in orthopedic and elective trauma surgery.
      RESULTS: In this investigation the established methods such as controlled
      hypotension (spine surgery), arrest of blood supply (extremity surgery) and the
      following methods of autotransfusion have been examined: acute normovolemic
      hemodilution (ANH), intra- (Cell-Saver, Haemonetics Corp.) and postoperative
      autotransfusion, autologous donor plasmapheresis and autologous predeposit.
      CONCLUSIONS: Using this method it is possible to reduce homologous blood
      transfusions particularly in elective procedures such as orthopedic surgery and
      elective trauma surgery to a minimum.

PMID- 14968395
TI  - Intraoperative imaging using a mobile computed tomography scanner.
AB  - OBJECTIVE: The radicality of tumour removal in patients suffering from glioma is
      discussed to be an important factor for longer survival times. Therefore
      intraoperative imaging modalities like magnetic resonance imaging (MRI), computed
      tomography (CT) and ultrasound (US) are tested in many neurosurgical facilities
      for clinical use. In our department a mobile CT for intraoperative applications
      is used for this purpose since 1999. The handling and useful application of the
      mobile CT scanner as well as results without intraoperative imaging are
      discussed. MATERIAL AND METHODS: 470 CT scans with the mobile CT were
      accomplished, including 270 cases of neuronavigation planning, 76 cases of
      intraoperative scans, 48 cases of postoperative scans, 69 CT scans for
      stereotactic biopsy planning and control as well as 3 cases of emergency scanning
      in trauma patients and 4 spine applications. The results of the intraoperative CT
      scans are compared with those of the postoperative MRI scans. Additionally 87
      patients with glioma were evaluated. These patients underwent surgery without
      intraoperative imaging. RESULTS: In 27 out of 43 patients with glioma residual
      tumour was detected with intraoperative CT. In 13 cases the surgery was resumed
      to complete resection, in 14 cases the operation was not continued due to close
      vicinity to eloquent areas or difficulties in image interpretation. In 44 cases
      the results of intraoperative CT and postoperative MRI were compared. In 6 cases
      the MRI demonstrated residual tumour in contrast to the results of the CT scans.
      In 3 cases the tumour removal could have been more complete (6.8 %). In 87 cases
      glioma surgery was performed without intraoperative CT. In 6 cases a more
      complete tumour removal could have been performed (6.9 %) according to the
      results of postoperative MRI. CONCLUSION: Intraoperative imaging with a mobile CT
      scanner is a good method for detection of residual tumour. The CT scanner can be
      integrated in an operative setting without problems. Although intraoperative
      imaging can be helpful in some selected cases, most of the neurosurgical
      procedures can be well performed with proper neuronavigation planning.

PMID- 14968396
TI  - Intraoperative three-dimensional reconstruction of power Doppler vascular images.
AB  - We have developed a simple method for reconstructing a three-dimensional (3D)
      image in the operating room from sequentially scanned intraoperative two
      dimensional (2D) power Doppler images using a personal computer and commercially
      available software. During three operations, 2 for cerebral aneurysm and 1 for
      cerebral tumor, intracranial vessel images were digitally transferred to a
      personal computer by freehand scanning over the dura mater or surface of the
      brain with a 7.5-MHz linear probe. A series of 2D images were converted to a
      smaller file, and 3D image was reconstructed with volume-rendering software. It
      took about 15 minutes to reconstruct of the initial 3D image. In the cases of
      cerebral aneurysm, the vessels connected to the lesion or running nearby were
      easily identified on the image. In the tumor case, the anatomical relation
      between the vascular structures and the tumor was clear. This simple 3D
      reconstruction method provides spatial information about intracranial vascular
      structures that is useful in intraoperative surgical planning.

PMID- 14968397
TI  - LINAC radiosurgery in recurrent Cushing's disease after transsphenoidal surgery:
      a series of 5 cases.
AB  - INTRODUCTION: Oversecretion of ACTH from pituitary adenomas is associated with
      morbidity and reduced life expectancies. We hypothesized that radiosurgical
      treatment may provide effective tumour and hormonal control associated with
      minimal pituitary insufficiency. METHOD: Data of five patients who underwent
      LINAC radiosurgery for recurrent or residual Cushing's disease between 1999 and
      2002 were prospectively collected. RESULT: Follow-up period ranged from 27 to 49
      months (mean 38 months). All patients attained remission in 6-18 months (mean 8.4
      months). One patient (20 %) developed biochemical recurrence 12 months after
      remission. One patient (20 %) developed hydrocortisone deficiency 24 months after
      radiosurgery. None of the patients had new visual field defect detected on follow
      up. CONCLUSION: In this small case series, LINAC radiosurgery was shown to be an
      effective and safe treatment of persistent or recurrent Cushing's disease
      following transsphenoidal surgery. Long-term follow-up and larger patient series
      is recommended for further clarification.

PMID- 14968398
TI  - Endoscopic management of supratentorial ventricular neurocysticercosis: case
      series and review of the literature.
AB  - OBJECTIVE: Despite the increasing popularity of neuroendoscopy, scarce
      documentation exists in the literature regarding successes and failures of this
      treatment modality for ventricular cysticercosis. Since July 2000, we instituted
      a specific endoscopic strategy for select patients with supratentorial
      ventricular disease. The goals of the strategy were to 1) remove ventricular
      cysts; 2) employ internal CSF diversion procedures for hydrocephalus to avoid
      shunting, and; 3) elude open surgical procedures. METHODS: A retrospective
      analysis of the charts of 7 patients managed with an endoscope for symptomatic
      hydrocephalus and supratentorial ventricular cysts was performed. A description
      of our management plan is given. RESULTS: From July 2000 through July 2002, we
      successfully resected all supratentorial ventricular cysts in 7 patients with an
      endoscope and employed three septostomies and four third ventriculostomies in the
      same sitting. None of the seven patients required shunting or further surgery to
      date. No case of postoperative ventriculitis occurred despite an 86 % cyst
      rupture rate. One cyst adjacent to the left foramen of Monro, which was
      successfully resected, produced significant intraventricular bleeding during
      surgical dissection. This patient developed akinetic mutism postoperatively,
      which improved with bromocriptine. The follow-up period was 16 months (range, 10 
      24 months). CONCLUSIONS: The ease of performing septostomies and third
      ventriculostomies in conjunction with cyst removal makes these procedures
      appealing and practical for most cases of ventricular cysticercosis.

PMID- 14968399
TI  - Endoscopic endonasal management of invasive skull base mucocele: report of two
      cases.
AB  - Two cases of massive erosive skull base sphenoid mucocele are reported. Even if
      intra-sphenoid mucoceles are an ENT pathology, when extensive they become of
      neurosurgical interest. An endoscopic minimally invasive procedure was performed
      in both cases with an excellent outcome. Patient 1 presented with several years
      of retro-orbital bilateral pain and several months of purulent pharyngeal leak.
      CT scan and MRI imaging showed an extensive erosive intra-sphenoid mass, with
      peripheral contrast enhancement. Patient 2 was referred because of several months
      of frontal headache and decreased left visual acuity. A wide intra-sphenoid mass
      was evident at CT scan and MRI. This mass included an anterior compartment,
      hyperintense on both T (1)- and T (2)-weighted images, and a posterior part,
      hypointense on T (1)- and hyperintense on T (2)-weighted images. A pure
      endoscopic endonasal one nostril pure procedure was performed in both cases.
      Endoscopic technique has been shown to be an easy and minimally invasive
      procedure. It should be the treatment of choice in case of invasive skull base
      mucocele in order to avoid blind damage of vasculo-nervous structures which are
      not protected by the bone, extensively eroded by the lesion.

PMID- 14968400
TI  - Surgical strategies for treatment of giant or large intracranial aneurysms: our
      experience with 139 cases.
AB  - Giant or large intracranial aneurysms are the vascular neurosurgeon's greatest
      challenge. At our department, we have treated one hundred and thirty nine
      patients with giant or large intracranial aneurysms between 1975 and 2001. These
      included 37 partially thrombosed giant aneurysms. 75 aneurysms were giant (> 2.5
      cm) and 64 were large aneurysms (2-2.5 cm). Three-dimensional computed tomography
      angiograms were performed in patients besides MRI angiography and digital
      subtraction angiography. These were found to be very valuable in the preoperative
      assessment of surgical anatomy of the aneurysm with respect to the branch
      arteries and perforators origin besides knowing the relations to the skull base.
      With our experience in surgical treatment of these 139 cases, we find that the
      basic technique is trapping and evacuation and not just clipping of the aneurysm
      neck but also reconstruction of the artery bearing the aneurysm, especially with
      wide-necked aneurysms. Use of multiple clipping, tandem clipping or dome clipping
      as per the intraoperative situation, is very helpful in dealing with giant
      aneurysms as also is the use of different types of clips like fenestrated clip
      with straight clip (combination clipping), booster clip, dome clips etc. While
      selecting surgical strategy for partially thrombosed giant aneurysm, securing the
      neck is most important. If the neck is too narrow to reconstruct, aneurysmectomy
      with anastomosis is one of the surgical strategies. An extracranial intracranial
      bypass should be considered in cases where clipping or parent artery ligation is
      expected to be associated with compromise of cerebral circulation.

PMID- 14968401
TI  - Factors leading to hydrocephalus after aneurysmal subarachnoid hemorrhage.
AB  - Hydrocephalus is not a rare complication following aneurysmal subarachnoid
      hemorrhage. Hydrocephalus following subarachnoid hemorrhage can progress acutely
      (0-3 days), subacutely (4-13 days) or chronically (after 13 days). The
      predisposing factors leading to hydrocephalus after subarachnoid hemorrhage are
      not known exactly. This study assessed the predictive factors for the development
      of this condition. All patients presenting with subarachnoid hemorrhage between
      1992-2001 were evaluated. All of them had initial computed tomography (CT) and
      hydrocephalus was diagnosed on CT scans. Age, gender, preexisting diabetes
      mellitus and hypertension, neurological state according to the Hunt and Hess
      scale at admission, Fischer grade on CT, the presence of intraventricular
      hemorrhage and localization of aneurysm were analyzed to see if there was any
      meaningful relationship between hydrocephalus and these factors. One hundred and
      fourteen patients with aneurysmal subarachnoid hemorrhage were evaluated. The
      incidence of hydrocephalus was 28.1 %. The incidence for acute hydrocephalus was
      18.4 %, for subacute 5.2 % and for chronic 4.3 %. Sixty-nine percent of patients
      with hydrocephalus were graded as 3, 4 or 5 according to the Hunt and Hess scale
      on admission. Fifty-five percent of patients with hydrocephalus were graded as 3
      and 4 according to Fisher grade on initial CT scan. Preexisting diabetes, higher
      Fisher grade and intraventricular hemorrhage were statistically significant
      predictors for the development of hydrocephalus. But only preexisting diabetes
      and higher Fisher grade were independent predictors according to multivariate
      analyses.

PMID- 14968402
TI  - Microsurgical therapy of symptomatic lumbar juxta facet cysts.
AB  - OBJECTIVE: Symptomatic lumbar juxta facet cysts (ganglion and synovial cysts)
      (JFC) are uncommon lesions of the spine, causing radiculopathy and low back pain.
      The authors present their experiences with microsurgically treated JFC. This rare
      pathology is discussed with special focus on therapeutic concepts and long-term
      outcome. METHOD: The records of 27 patients with symptomatic lumbar JFC were
      retrospectively reviewed. The clinical data and diagnostic procedures were
      evaluated. The patient age ranged from 38 to 83 years (mean 61 years). Treatment
      consisted exclusively of microsurgical excision of the cysts after partial
      hemilaminectomy. The early surgical results were evaluated 6 weeks after surgery.
      For assessment of late surgical results (mean follow-up period 70 months), the
      Finneson and Cooper outcome scale was used. RESULTS: After 6 weeks, the
      preoperative symptoms were improved in 25 patients (93 %). Long-time follow-up
      was available in 23 patients. Good (pain improved and able to function well) to
      excellent (pain free and able to function well) results were still found in 83 %
      of the patients. With exception of 2 small asymptomatic dural tears and a slight
      temporary increase of the preoperative paresis, no surgical complications were
      encountered. One JFC recurred after 4 months and required re-operation with
      finally good outcome. CONCLUSION: Adequate and definitive treatment in
      symptomatic JFC consists in microsurgical resection. A partial hemilaminectomy is
      sufficient for surgical exposure. Excellent long-term outcome can be achieved.
      Recurrences and surgical complications are rare.

PMID- 14968403
TI  - Overdrainage after endoscopic third ventriculostomy: an unusual case of chronic
      subdural hematoma--case report and review of the literature.
AB  - Endoscopic third ventriculostomy is considered a safe technique for the treatment
      of obstructive hydrocephalus. However, the literature contains several reports of
      complications related to this procedure. We describe a case of chronic subdural
      hematoma (CSDH) after ETV, which required surgical evacuation, in a 69-year-old
      male patient completely asymptomatic up to the control MRI four weeks after the
      operation. We believe this unusual complication could result from the ICP changes
      caused by ETV. In our opinion, successful ETV gives a boost to CSF absorption,
      and overdrainage may evolve also in endoscopic treatment of obstructive
      hydrocephalus. This situation could be the starting point of the subdural
      collection. We review the literature and discuss the causes that may lead to CSDH
      after ETV procedure.

PMID- 14968404
TI  - Spontaneous dissecting aneurysm of middle cerebral artery: a case report with
      review of the literature.
AB  - We report a case of a dissecting aneurysm of the middle cerebral artery (MCA) and
      its treatment strategies. A 50-year-old male patient presented with occipital and
      neck pain for 2 days. CT scan revealed subarachnoid hemorrhage (SAH) in the
      region of the right sylvian fissure. A left carotid angiogram showed a dissecting
      aneurysm of the left MCA (M1). He was treated surgically by a pterional trans
      sylvian approach. Clipping was done along with additional reinforcement by
      wrapping to completely obliterate the neck of the aneurysm. On reviewing the
      literature, we think that dissecting aneurysms seem to be one of the important
      causes of SAH and cerebral infarction of unverified origin. If an MCA dissecting
      aneurysm is identified, especially located in the proximal portion, surgical
      treatment must be considered. These patients merit a close follow-up.

PMID- 14968405
TI  - Cerebral aneurysms in Behcet's disease: a case report.
AB  - A 42-year-old male patient was surgically treated for two cerebral aneurysms, 18
      months later he developed manifestations of Behcet's disease. Lack of clinical
      manifestations as well as angiographic evidence of vasculitis at the time of the
      cerebral aneurysmal disease argue against the possibility that the aneurysms were
      complications of the neural involvement of Behcet's disease.

PMID- 14968406
TI  - Epipteric bones in the pterion may be a surgical pitfall.
AB  - BACKGROUND: The pterion, the most commonly used neurosurgical landmark, is
      defined as the junction of frontal, parietal, and greater wing of the sphenoid
      and the squamous part of temporal bones. Our aim was to identify the variations
      of the pterion which may be a potential surgical pitfall. METHODS: Both sides of
      300 adult skulls were examined but 110 sides were eliminated since their pterion
      could not be identified owing to a damage. The shortest distance between the
      lateral orbital rim and the most anterior junction of the four bones forming the
      pterion was measured on all sides. RESULTS: Out of 490 sides the pterion was
      found to contain epipteric bones in 44 (9 %), and in these skulls the most
      anterior junction of the bones may be as close as 16 mm to the lateral orbital
      rim. CONCLUSION: In skulls with an epipteric bone variation, particularly the
      anterius and proprium types; the pterion can mistakenly be assessed to be at the
      most anterior junction of bones and a burr hole placed over there may cause
      inadvertent penetration into the orbit.

PMID- 14968407
TI  - Contralateral inferior petrosal sinus approach for transvenous embolization of a
      dural arteriovenous fistula at isolated jugular bulb. Technical case report.
AB  - A contralateral inferior petrosal sinus approach is described for the successful
      treatment of a case of a dural arteriovenous fistula at an isolated right jugular
      bulb presenting with chemosis. A microcatheter could be inserted into the right
      jugular bulb from the left jugular bulb through the left inferior petrosal sinus,
      basilar sinus on the dorsum sellae, and the right inferior petrosal sinus. This
      unusual approach represents an alternative route to the jugular bulb.

PMID- 14968408
TI  - Endoscopic removal of thalamic hematoma: a technical note.
AB  - OBJECT: To minimize invasiveness, an endoscopic surgical technique under
      stereotactic guidance is described for removal of thalamic hematoma. SURGICAL
      TECHNIQUE: A burr hole is placed at a point 3 cm above the glabella and 3 cm
      lateral from the midline. A transcortical transventricular puncture is performed
      with a stainless steel tube under stereotactic guidance. The tube is mounted to a
      metal holder. Through this tube, a rod-lens working channel endoscope and
      surgical instruments are inserted for visualization of the thalamus and
      evacuation of the hematoma. Compared with the endoscopic approach through the
      shortest distance of viable brain tissue, this technique allows removal of the
      hematoma in the ventricular space and thalamus simultaneously. The case of one
      patient with thalamic hemorrhage and obstructive hydrocephalus, caused by an
      intraventricular blood clot, is reported for surgical demonstration. CONCLUSION:
      An endoscopic technique for removal of thalamic hematoma with the aid of
      stereotactic guidance, which allows precise targeting of the lesion, is reported.

PMID- 14968409
TI  - Reconstruction of burr hole by using autologous button-shaped graft harvested
      from inner table of craniotomy flap: technique and clinical result.
AB  - Patients who underwent craniotomy occasionally complain about the postoperative
      cosmetic appearance at the site of burr holes on the scalp. This problem occurs
      as a result of depletion of the skin into the unreconstructed burr holes. Some
      materials have been developed for reconstruction of craniotomy burr holes. To
      prevent the postoperative cosmetic deformity, the authors developed a button
      shaped autologous bone graft harvested from the inner table of craniotomy flap.
      Clinical application of this method is described.

PMID- 14968410
TI  - Chronic subdural haematoma treatment with a rigid endoscope.
AB  - Surgical treatment is the method of choice in cases of chronic subdural haematoma
      -as a rule: trephination, drainage with lavage, or repeated drainage (drain
      reinsertion where the haematoma has been evacuated insufficiently). A poorly
      manageable but non-negligible group is made up of patients (about 5-12 % of all
      cases) where the less invasive methods of choice keep failing. The equally mini
      invasive endoscopic technique appears to be one of the suitable therapeutical
      approaches before resorting to open-surgery revision. The adapted technique of
      rigid endoscope insertion permitting sufficient revision and treatment of the
      subdural space concerned is presented. The method is demonstrated on three case
      reports where routine trephination with lavage, drainage and repeated drain
      insertion failed. A very good improvement in clinical condition and graphic
      findings was achieved in two patients. In the remaining one, the neurological
      lesion improved ad integrum despite a tiny residual haematoma as visualized by
      CT. Two weeks later, a clinical relapse had developed and the patient was treated
      with new trephination and drain reinsertion. The technical aspects of the
      modification of the endoscopic technique are discussed: stressing the advantages
      or low-degree invasiveness, scope for keeping intact the inner membrane of the
      haematoma and avoiding direct invasion of the cerebral tissue. The limits of the
      method are discussed as well. The authors regard this method as a useful addition
      to the surgical armamentarium, especially in cases of chronic subdural haematomas
      resisting conventional approaches.

PMID- 14968411
TI  - Age-related macular degeneration: a high-resolution genome scan for
      susceptibility loci in a population enriched for late-stage disease.
AB  - Age-related macular degeneration (AMD) is a complex multifactorial disease that
      affects the central region of the retina. AMD is clinically heterogeneous,
      leading to geographic atrophy (GA) and/or choroidal neovascularization (CNV) at
      advanced stages. Considerable data exists in support of a genetic predisposition
      for AMD. Recent linkage studies have provided evidence in favor of several AMD
      susceptibility loci. We have performed a high-resolution (5-cM) genome scan of
      412 affected relative pairs that were enriched for late-stage disease (GA and/or
      CNV). Nonparametric linkage analysis was performed using two different diagnostic
      criteria and also by dividing the affected individuals according to GA or CNV
      phenotype. Our results demonstrate evidence of linkage in regions that were
      suggested in at least one previous study at chromosomes 1q (236-240 cM in the
      Marshfield genetic map), 5p (40-50 cM), and 9q (111 cM). Multipoint analysis of
      affected relatives with CNV provided evidence of additional susceptibility loci
      on chromosomes 2p (10 cM) and 22q (25 cM). A recently identified Gln5345Arg
      change in HEMICENTIN-1 on chromosome 1q25 was not detected in 274 affected
      members in the restricted group with AMD, 346 additional patients with AMD, and
      237 unaffected controls. Our results consolidate the chromosomal locations of
      several AMD susceptibility loci and, together with previous reports, should
      facilitate the search for disease-associated sequence variants.

PMID- 14968412
TI  - Cytology of human ovarian surface epithelial brushings.
AB  - BACKGROUND: The human ovarian surface epithelium (HOSE) is the putative source of
      ovarian epithelial cancer, the most lethal gynecologic malignancy that affects
      women in the United States. The current study was designed to provide a database
      of normal HOSE cell features for diagnostic and research applications. METHODS:
      HOSE was harvested from 42 women undergoing laparoscopy or laparotomy for benign
      gynecologic disorders, infertility problems, or pregnancy. Of the 42 women, 12
      were postovulatory and 20 were receiving hormonal regimens. Cells were harvested
      with a sterile brush inserted through a laparoscopic port or with a sterile cell
      scraper at laparotomy. RESULTS: Two HOSE populations were identified, ranging in
      size from 8 to 10 microm and from 15 to 20 microm, respectively. The cells
      measuring 15-20 microm exhibited slight anisonucleosis, more prominent nucleoli,
      fine cytoplasmic metachromasia, and an overall reparative or squamoid morphology.
      Cells were single or arranged in small clusters, sheets, or papillae. They
      coexpressed cytokeratin and vimentin but did not overexpress p53. Cellularity and
      proliferation (up to 3.2% +/- 0.8) were higher and papillae more frequent in
      postovulatory and cyst-bearing ovaries, including polycystic ovaries, suggesting
      underlying ovarian or hormonal influences. Representative HOSE brushings yielded
      a mean of 23,133 cells per patient (range, 4250-64,500 cells), equivalent to an
      estimated 0.58, 0.46, and 0.14 microg of nuclear protein, cell RNA, and nuclear
      DNA, respectively. Within 7-10 days of explantation, HOSE cells formed confluent
      monolayers with immunohistochemical and ultrastructural epithelial features.
      CONCLUSIONS: The current study defined baseline features of HOSE cells important
      to pathologists and clinicians evaluating women at risk for ovarian epithelial
      cancer and to researchers investigating the pathobiology of this aggressive
      gynecologic malignancy.

PMID- 14968413
TI  - Comparison of hybrid capture 2 with in situ hybridization for the detection of
      high-risk human papillomavirus in liquid-based cervical samples.
AB  - BACKGROUND: The performance of two commercially available detection systems for
      high-risk HPV (hrHPV), Hybrid Capture 2 (HC2) and in situ hybridization (ISH),
      were compared on cervical scrapings. METHODS: Using general primer (GP)-mediated
      GP5+/6+-polymerase chain reaction (PCR)-enzyme immunoassay and reverse line blot
      genotyping, 76 liquid-based cervical samples were identified with > or = 1 of the
      12 hrHPV types present in the probes of the HC2 and ISH assays. The positivity
      rate of the assays and the HC2 viral load were determined and related to
      cytologic findings (n = 76 samples) and histologic findings (n = 43 samples).
      RESULTS: Overall, HC2 scored significantly more samples positive compared with
      ISH (P < 0.01). Seventy-four of 76 samples (97%) were positive according to HC2.
      Forty-six of 76 samples (61%) were positive according to ISH, including 80% and
      70% of samples that were classified cytologically as moderate dysplasia and
      severe dysplasia, respectively. All women with underlying cervical
      intraepithelial neoplasia (CIN) lesions and 67% of women without CIN had positive
      HC2 samples. ISH scored 33%, 66%, 88%, and 73% of samples positive of women with
      no CIN, Grade 1 CIN (CIN 1), CIN 2, and CIN 3, respectively. The HC2 viral load
      was significantly higher in women who had a cytologic diagnosis of dysplasia (P <
      0.01) and in women who had an underlying diagnosis of CIN (P < 0.01) compared
      with women who had neither. In addition, the viral load was significantly higher
      in ISH positive samples compared with ISH negative samples (P < 0.01).
      CONCLUSIONS: An increased HC2 viral load was associated with an increased chance
      of underlying high-grade CIN disease in women who tested hrHPV GP5+/6+-PCR
      positive. Moreover, although positive ISH results were associated with an
      increased overall viral load in the sample, the analytic sensitivity of ISH was
      too low to detect all women with prevalent high-grade CIN.

PMID- 14968414
TI  - Anorectal cytology as a screening tool for anal squamous lesions: cytologic,
      anoscopic, and histologic correlation.
AB  - BACKGROUND: Anorectal cytology has been increasingly used as a screening method
      for anal squamous lesions, particularly in high-risk, homosexual, patients with
      human immunodeficiency virus infection. The diagnostic cytologic, anoscopic, and
      histologic criteria bear some resemblance to the criteria used in cervicovaginal
      samples with few differences. It is important to recognize these differences
      because they can lead to an erroneous diagnosis of dysplasia and unnecessary
      procedures. METHODS: Seventy-eight anorectal cytology specimens from 51 patients
      were reviewed blindly. Of the 51 patients, 33 were HIV positive. The cytology
      specimens consisted of 75 ThinPrep (Cytyc, Boxborough, MA) and 3 conventional
      Papanicolaou-stained smear specimens. The revised diagnosis was compared with the
      original diagnosis, corresponding histology specimens, and anoscopic results,
      when available. RESULTS: Six specimens were unsatisfactory for review. The
      revised diagnosis was negative in 15 patients, atypical squamous cells of
      undetermined significance in 3 patients, low-grade squamous intraepithelial
      lesions in 24 patients, high-grade squamous intraepithelial lesions in 28
      patients, and squamous cell carcinoma (SQC) in 2 patients. Five patients with an
      original diagnosis of SQC had the diagnosis revised upon review of their
      specimens. It is noteworthy that these five specimens showed the presence of
      atypical parakeratotic cells. Thirty-two patients had anoscopic evaluation and 30
      patients had histologic correlation. Twenty-seven patients with abnormal
      anoscopic findings had confirmed abnormal histologic findings. Twenty- five of
      the 32 (78%) patients had abnormal cytology that correlated with abnormal
      anoscopic findings. CONCLUSIONS: Anorectal cytology is an accurate method for
      screening patients for anal squamous lesions. Atypical parakeratotic cells
      represent a potential pitfall. Anoscopy is important in confirming the presence
      of a lesion, but only a biopsy can accurately determine the grade of a lesion.

PMID- 14968415
TI  - Cytologic features and histologic correlations of microacinar and microtrabecular
      types of well-differentiated hepatocellular carcinoma in fine-needle aspiration
      biopsy.
AB  - BACKGROUND: Well-differentiated hepatocellular carcinoma (HCC) in fine-needle
      aspiration (FNA) biopsy is characterized by trabeculae three or more cells thick
      wrapped by peripheral endothelium. The authors encountered another pattern that
      did not fulfill these classic criteria for malignancy yet was proven to be HCC in
      clinical follow-up. The objective of this study was to characterize the cytologic
      features of this pattern with histologic correlations. METHODS: Over a period of
      6.5 years, 14 of 123 cases (11.4%) of HCC from 428 liver aspirates showed the
      unusual pattern. Their cytologic features were compared with 14 cases of
      nonneoplastic liver on FNA smears that were processed with Ultrafast Papanicolaou
      stain, and their histologic features were compared on cell blocks with
      hematoxylin and eosin stain and reticulin stain. RESULTS: The unusual type of
      well differentiated HCC in FNA smears was characterized by numerous, small
      hepatocytes with minimal nuclear atypia but reduced cytoplasm, grouped together
      in microacini of five or more cells and microtrabeculae one or more cells thick
      of irregular thickness with no apparent peripheral endothelium. Transgressing
      capillaries were found when the smears were inspected carefully. In histology
      nine cases that were the compact type of HCC, two cases that were the microacinar
      type of HCC, and three cases that were the microtrabecular type of HCC. All FNAs
      showed deficient reticulin framework. All 14 cases of nonneoplastic liver
      aspirate were characterized by the presence of large tissue fragments that were
      resistant to smearing. CONCLUSIONS: Well differentiated HCC may present as
      microtrabeculae of irregular thickness one or more cells thick with inapparent
      peripheral endothelium or as microacini mimicking neuroendocrine carcinoma.

PMID- 14968416
TI  - Optimal fixation conditions for immunocytochemical analysis of estrogen receptor
      in cytologic specimens of breast carcinoma.
AB  - BACKGROUND: The techniques for immunostaining estrogen receptor (ER) in cytologic
      specimens have varied, as have the detection rates. The authors compared various
      fixation methods for their effect on ER detection in cytologic smears of breast
      carcinoma. METHODS: Smears were prepared by gently scraping the cut surfaces of
      47 resected breast carcinoma specimens and placing immediately in 1 of the
      following conditions: 1) a sequence of 10% formalin-methanol-acetone fixatives at
      -20 degrees C (Abbott method); 2) 10% formalin at room temperature; and 3)
      Carnoy's fixative at room temperature and then Papanicolaou stained (Carnoy's
      Pap). Destaining of Carnoy's-Pap smears (Carnoy's-dPap) was initially attempted
      before ER staining. One set of smears was also air-dried for 3 minutes before
      using the Abbott method. Smears and corresponding tissue sections were
      immunostained with anti-ER antibody 6F11 using a similar protocol except for
      antigen retrieval, which was not initially applied on cytologic slides. All the
      ER-negative smears that had been fixed with 10% formalin or Carnoy's-Pap were
      restained after antigen retrieval. Agreement between cytologic and histologic
      findings was expressed by both concordance and the kappa coefficient. RESULTS: ER
      detection in smears processed with the Abbott method correlated best with
      findings from tissue samples, with an overall correlation of 91.5% (kappa =
      0.80). Findings from air-dried smears were less optimal (concordance, 84.4%;
      kappa = 0.65), followed by Carnoy's-Pap (concordance, 71.4%; kappa = 0.45),
      formalin (concordance, 31%; kappa = 0.05), and Carnoy's-dPap (concordance, 29.4%;
      kappa = 0.04). Antigen retrieval converted most of the ER-negative smears to
      positive (18 of 20 smears in formalin and 6 of 8 smears in Carnoy's-Pap), leading
      to a final concordance of 93% and kappa = 0.83 for both conditions. Antigen
      retrieval also led to stronger staining intensity without causing false
      positivity. CONCLUSIONS: Antigen retrieval was found to greatly improve ER
      immunodetectability and staining intensity in formalin-fixed and Carnoy's-Pap
      smears. The former may offer an alternative to the Abbott method because of its
      easiness and the latter can be reliably used in archival Pap-stained smears for
      retrospective analysis of ER. Air-drying, destaining Pap smear, and fixation in
      formalin or Carnoy's-Pap without antigen retrieval are not recommended.

PMID- 14968417
TI  - Diagnostic and prognostic use of DNA image cytometry in cervical squamous
      intraepithelial lesions and invasive carcinoma.
AB  - In the fight against cervical malignancy and its precursors, several adjuvant
      diagnostic methods have been proposed to increase the accuracy of cytologic and
      histologic diagnoses. Because chromosomal aneuploidy has been accepted as an
      early key event in tumorigenesis caused by genetic instability, the cytometric
      equivalent of chromosomal aneuploidy detected by DNA image cytometry (DNA-ICM)
      may serve as a marker of neoplasia. During the last decade, the appearance of a
      new generation of hardware with high processing and storage capacities, together
      with the development of appropriate software, has facilitated the development of
      high-performance DNA-ICM systems. International consensus on the clinical
      application of DNA-ICM has been reached. According to the statements of Task
      Force 8 of the International Consensus Conference on the Fight Against Cervical
      Cancer, indications for DNA-ICM include the identification of prospectively
      malignant cells in squamous intraepithelial lesions (SILs) and atypical squamous
      cells of undetermined significance (ASCUS). The European Society of Analytical
      Cellular Pathology consensus reports on DNA-ICM have provided standardized
      technical details on performance, terms, and algorithms for diagnostic data
      interpretation and quality-assurance procedures. Increasing biologic evidence and
      clinical data have confirmed the utility of DNA-ICM as an adjuvant method
      suitable for determining the diagnosis and prognosis of cervical intraepithelial
      lesions and invasive carcinoma. Patients with ASCUS and low-grade SIL diagnoses
      that reveal DNA euploidy may return for normal screening intervals, whereas the
      detection of DNA aneuploidy indicates that these lesions should be removed.
      Formerly a research tool, today, standardized DNA-ICM has become a useful and low
      cost laboratory method to establish objectively and reproducibly an early
      diagnosis of prospectively progressive cervical intraepithelial lesions at a high
      quality level. DNA-ICM may further contribute to the monitoring of treatment in
      patients with invasive cervical malignancies.

PMID- 14968418
TI  - Fine-needle cytology and flow cytometry immunophenotyping and subclassification
      of non-Hodgkin lymphoma: a critical review of 307 cases with technical
      suggestions.
AB  - BACKGROUND: Flow cytometry (FC) is a useful adjunct to fine-needle aspiration
      cytology (FNC) in evaluating lymphoproliferative disorders. The authors present a
      critical review of 307 lymph nodal and extra lymph nodal lymphoproliferative
      disorders that were diagnosed with FNC and FC. METHODS: FC was performed over a 4
      year period on 185 palpable and 122 impalpable lymph nodal and extra lymph nodal
      lymphoproliferative processes under ultrasound or computed tomography guidance.
      FC was performed using the following fluoresceinated antibodies: CD3, CD4/CD8,
      CD2/CD7/CD3, CD5/CD10/CD19, CD19/kappa/lambda, FMC7/CD23/CD19, CD38/CD56/CD19,
      and bcl-2. The series included 15 inadequate, 10 suspicious, and 135 benign
      reactive hyperplasias (BRHs); 70 primary non-Hodgkin lymphomas (NHLs), and 77
      recurrent NHLs (rNHLs). FC/FNC diagnoses of suspicious, NHL, and rNHL were
      controlled either histologically or clinically or by the interphase fluorescence
      in situ hybridization demonstration of t(11;14)(q13;q32) in two cases of mantle
      cell lymphoma. BRHs were controlled by follow-up. Sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) of the
      FC/FNC diagnoses of NHL, rNHL, and BRH were calculated as well as the
      identification of specific subtypes among the small- and medium-sized cells.
      RESULTS: Statistical analysis showed 93% sensitivity, 100% specificity, 100% PPV,
      and 91% NPV in NHL, rNHL, and BRH discrimination. The subclassification of small
      cell and medium-sized NHLs showed 63% sensitivity, 88% specificity, 95% PPV, and
      37% NPV. CONCLUSIONS: FC applied to FNC enhanced the precision of cytologic
      diagnosis in lymph nodal and extra lymph nodal lymphoproliferative disorders and
      allowed further subclassification in more than half of the cases, thus avoiding
      invasive surgical biopsies in many patients.

PMID- 14968419
TI  - Analysis and significance of linear enamel hypoplasia in Plio-Pleistocene
      hominins.
AB  - This study of linear enamel hypoplasia (LEH) in Plio-Pleistocene hominins builds
      on a previous study (Guatelli-Steinberg [2003] Am. J. Phys. Anthropol. 120:309
      322) that focused on LEH in early South African hominins. The present study is
      more comprehensive, encompassing dental specimens of hominins from East Africa as
      well, including early Homo. As a developmental defect of enamel, LEH is used in
      anthropological contexts to reveal information about physiological stress.
      However, intrinsic aspects of enamel development and morphology can affect the
      expression of LEH, complicating efforts to understand the significance of these
      defects. In this study, the analysis of LEH is conducted with respect to enamel
      development and morphology. It is predicted that Paranthropus should have fewer
      defects on its canine teeth than Australopithecus and Homo, owing to its
      abbreviated period of enamel formation. This prediction is supported:
      Paranthropus has statistically significantly fewer defects per canine than
      Australopithecus and Homo. The previous study demonstrated that despite the wider
      spacing of perikymata on the teeth of South African Paranthropus, defects on the
      canine teeth of this genus were not wider than those of Australopithecus. A
      multiple linear regression analysis in that study, as well as a separate analysis
      in the present study, indicate that the number of perikymata within defects is a
      better predictor of defect width than perikymata spacing. In this study, it was
      additionally found that the average number of perikymata within Australopithecus
      defects is statistically significantly greater than it is in Paranthropus, thus
      explaining why Paranthropus defects are not wider than those of Australopithecus.
      The biological significance of this difference in the number of perikymata within
      the defects of Australopithecus and Paranthropus is considered in light of
      several factors, including: 1) the possibility that other intrinsic attributes of
      enamel morphology may be involved (specifically the faster extension rates of
      Paranthropus that result in shallower defects), 2) generic differences in the
      canalization of enamel development, and 3) generic differences in the duration of
      disruptions to enamel growth.

PMID- 14968420
TI  - Hypothesis for the causes and periodicity of repetitive linear enamel hypoplasia
      in large, wild African (Pan troglodytes and Gorilla gorilla) and Asian (Pongo
      pygmaeus) apes.
AB  - Repetitive linear enamel hypoplasia (rLEH) is often observed in recent large
      bodied apes from Africa and Asia as well as Mid- to Late Miocene sites from Spain
      to China. The ubiquity and periodicity of rLEH are not understood. Its potential
      as an ontogenetic marker of developmental stress in threatened species (as well
      as their ancient relatives) makes rLEH an important if enigmatic problem. We
      report research designed to show the periodicity of rLEH among West African Pan
      troglodytes (12 male, 32 female), Gorilla gorilla (10 male, 10 female), and
      Bornean and Sumatran Pongo pygmaeus (11 male, 9 female, 9 unknown) from
      collections in Europe. Two methods were employed. In the common chimpanzees and
      gorillas, the space between adjacent, macroscopically visible LEH grooves on
      teeth with two or more episodes was expressed as an absolute measure and as a
      ratio of complete unworn crown height. In the orangutans, the number of
      perikymata between episode onsets, as well as duration of rLEH, was determined
      from scanning electron micrographs of casts of incisors and canines. We conclude
      that stress in the form of LEH commences as early as 2.5 years of age in all taxa
      and lasts for several years, and even longer in orangutans; the stress is not
      chronic but episodic; the stressor has a strong tendency to occur in pulses of
      two occurrences each; and large apes from both land masses exhibit rLEH with an
      average periodicity of 6 months (or multiples thereof; Sumatran orangutans seem
      to show only annual stress), but this needs further research. This is supported
      by evidence of spacing between rLEH as well as perikymata counts. Duration of
      stress in orangutans averages about 6 weeks. Finally, the semiannual stressor
      transcends geographic and temporal boundaries, and is attributed to regular
      moisture cycles associated with the intertropical convergence zone modified by
      the monsoon. While seasonal cycles can influence both disease and nutritional
      stress, it is likely the combination of seasonal variation in fruiting cycles
      with specific stressors (malaria and/or intestinal parasites, especially
      hookworm) that results in this widespread phenomenon. This seasonal stress is
      sufficiently common and of long duration (6 weeks on average in orangutans) that
      we think rLEH may reflect significant stress in recent and, inferentially, fossil
      apes. Increasing seasonality may have impinged negatively on later Miocene apes,
      especially if they lacked a clear birth peak or seasonality in their reproductive
      cycles.

PMID- 14968421
TI  - Sagittal clefting of the body and other vertebral developmental errors in
      Canadian Inuit skeletons.
AB  - The objective of this study was to determine the expression, distribution in the
      column, and overall frequency of sagittal clefting of the vertebral body in the
      skeletons of two Canadian Inuit groups. One group, referred to as Thule-Historic,
      lived along the coast northwest of Hudson Bay, while the other, known as the
      Sadlermiut, were limited to Southampton Island and Coats Island north of Hudson
      Bay. The Thule-Historic people are thought to be the ancestors of the present-day
      Inuit of this region, whereas the much smaller, relatively isolated Sadlermiut
      became extinct during the winter of 1902-1903. The sagittal clefting results were
      also compared with those obtained for two other vertebral developmental problems,
      segmentation error and spina bifida. Sagittal clefting was found to occur with
      high frequency in the two Inuit series, especially in the region T6-T10.
      Segmentation errors were found to occur in approximately the same region of the
      column, while spina bifida produced a completely different pattern, occurring
      primarily at T11 and S1. The T11 involvement is limited to females, while S1
      involvement occurs primarily in males. Sagittal clefting and spina bifida occur
      in the same individual more frequently than sagittal clefting and segmentation
      error. Possibly reflecting the smaller population size and isolated location of
      the Sadlermiut, sagittal clefting was found with greater frequency and intensity
      in the skeletons of this group than in those of the Thule-Historic Inuit. Am J
      Phys Anthropol, 2003.

PMID- 14968422
TI  - Ontogenetic correlates of diet in Malagasy lemurs.
AB  - There is a well-documented relationship between development and other life
      history parameters among anthropoid primates. Smaller-bodied anthropoids tend to
      mature more rapidly than do larger-bodied species. Among anthropoids of similar
      body sizes, folivorous species tend to grow and mature more quickly than do
      frugivorous species, thus attaining adult body size at an earlier age. This
      pattern conforms to the expectations of Janson and van Schaik's "ecological risk
      aversion hypothesis," which predicts that rates of growth and maturation should
      vary in inverse relation to the intensity of intraspecific feeding competition.
      According to the ecological risk aversion hypothesis (RAH), species experiencing
      high intraspecific feeding competition will grow and mature slowly to reduce the
      risk of mortality due to food shortages. Species experiencing low levels of
      intraspecific feeding competition will shorten the juvenile period to reduce the
      overall duration of this high-risk portion of the life cycle. This paper focuses
      on development and maturation in lemurs. We show that folivorous lemurs (such as
      indriids) grow and mature more slowly than like-sized frugivorous lemurs (e.g.,
      most lemurids), but tend to exhibit faster dental development. Their dental
      developmental schedules are accelerated on an absolute scale, relative to
      craniofacial growth, and relative to particular life-history landmarks, such as
      weaning. Dental development has a strong phylogenetic component: even those
      lemurids that consume substantial amounts of foliage have slower dental
      development than those indriids that consume substantial amounts of fruit.
      Implications of these results for the RAH are discussed, and an explanation for
      this hypothesis' failure to predict lemur growth schedules is offered. We propose
      that the differing developmental schedules of folivorous and frugivorous lemurs
      may reflect different solutions to the ecological problem of environmental
      instability: some rely on a strategy of low maternal input and slow returns,
      while others rely on a strategy of high maternal input and fast returns.

PMID- 14968423
TI  - Sedentism, seasonality, and economic status: A multivariate analysis of maternal
      dietary and health statuses between pastoral and agricultural Ariaal and Rendille
      communities in northern Kenya.
AB  - This paper examines longitudinal data to assess the effects of the recent
      transition from pastoralism to sedentary agriculture for Ariaal and Rendille
      mothers in northern Kenya. Dietary, morbidity, and anthropometric data resulting
      from bimonthly repeated surveys of the pastoral community of Lewogoso and the
      sedentary agricultural community of Songa, covering the period from September
      1994-July 1995, were used to test two hypotheses: 1) that sedentism is associated
      with changes in diet, seasonality, morbidity, and socioeconomic differentiation,
      and 2) that these changes affect maternal body composition. The first hypothesis
      is partly supported, with starch replacing milk in the sedentary diet. Repeated
      measures multivariate analysis of variance revealed no seasonal effects for diet
      in the agricultural sample, while starch consumption was significantly affected
      by seasonality for the pastoral sample. The agricultural community also featured
      economic dietary disparities favoring wealthier mothers, while no such effect was
      found in the pastoral community. However, no seasonal or economic effects were
      found for morbidity patterns in either sample. The second hypothesis is also
      partially supported, as a generalized estimating equations analysis revealed
      differences in the way diet and economic strata influence maternal anthropometric
      values. Economic status was significantly associated with maternal arm-fat area
      in Lewogoso. Milk was a significant factor associated with maternal weight and
      arm-muscle area in Songa. These findings are discussed in light of development
      policy implications.

PMID- 14968425
TI  - Four permeases import proline and the toxic proline analogue azetidine-2
      carboxylate into yeast.
AB  - We have found that proline and the toxic proline analogue azetidine-2-carboxylate
      (AzC) are efficiently imported into Saccharomyces cerevisiae cells by four amino
      acid permeases, including two nitrogen-regulated permeases (PUT4 and GAP1) and
      two permeases that are regulated by the SPS sensor of extracellular amino acids
      (AGP1 and GNP1). In contrast to Agp1p, Gnp1p is not functionally expressed when
      cells are grown on media containing proline as sole nitrogen source. These
      findings have implications for the interpretation of studies using AzC to
      characterize nitrogen source-dependent regulation of amino acid uptake and of
      post-Golgi targeting and localization of amino acid permeases in yeast.

PMID- 14968426
TI  - Ady2p is essential for the acetate permease activity in the yeast Saccharomyces
      cerevisiae.
AB  - To identify new genes involved in acetate uptake in Saccharomyces cerevisiae, an
      analysis of the gene expression profiles of cells shifted from glucose to acetic
      acid was performed. The gene expression reprogramming of yeast adapting to a poor
      non-fermentable carbon source was observed, including dramatic metabolic changes,
      global activation of translation machinery, mitochondria biogenesis and the
      induction of known or putative transporters. Among them, the gene ADY2/YCR010c
      was identified as a new key element for acetate transport, being homologous to
      the Yarrowia lipolytica GPR1 gene, which has a role in acetic acid sensitivity.
      Disruption of ADY2 in S. cerevisiae abolished the active transport of acetate.
      Microarray analyses of ady2Delta strains showed that this gene is not a critical
      regulator of acetate response and that its role is directly connected to acetate
      transport. Ady2p is predicted to be a membrane protein and is a valuable acetate
      transporter candidate.

PMID- 14968427
TI  - Cloning and expression analysis of the ornithine decarboxylase gene (PbrODC) of
      the pathogenic fungus Paracoccidioides brasiliensis.
AB  - We describe the isolation and sequencing of PbrODC, the gene encoding ornithine
      decarboxylase (ODC) in Paracoccidioides brasiliensis. The gene contains a single
      open reading frame made of 1413 bp with a single intron (72 bp), and encodes a
      447 amino acid polypeptide with a predicted molecular weight of 50.0 kDa, an
      isoelectric point of 4.9 and a high similarity to other fungal ornithine
      decarboxylases. Functionality of the gene was demonstrated by transformation into
      a Saccharomyces cerevisiae odc null mutant. A phylogenetic tree generated with
      several fungal ODCs provided additional evidence to favour a taxonomic position
      for P. brasiliensis as an ascomycetous fungus, belonging to the order Onygenales.
      Expression of the PbrODC gene was determined by Northern analyses during growth
      of the mycelial and yeast forms, and through the temperature-regulated dimorphic
      transition between these two extreme phases. Expression of PbrODC remained
      constant at all stages of the fungal growth, and did not correlate with a
      previously observed increase in the activity of ornithine decarboxylase at the
      onset of the budding process in both yeast growth and mycelium-to-yeast
      transition. Accordingly, post-transcriptional regulation for the product of
      PbrODC is suggested.

PMID- 14968428
TI  - SRE1 and SRE2 are two specific steroid-responsive modules of Candida drug
      resistance gene 1 (CDR1) promoter.
AB  - CDR1 gene encoding an ATP-driven drug extrusion pump has been implicated in the
      development of azole-resistance in Candida albicans. Although the upregulation of
      CDR1 expression by various environmental factors has been documented, the
      molecular mechanism underlying such process is poorly understood. We have
      demonstrated earlier that the CDR1 promoter encompasses a large number of cis
      regulatory elements, presumably mediating its response to various drugs. In this
      study we have identified a novel steroid responsive region (SRR) conferring beta
      oestradiol and progesterone inducibility on the CDR1 promoter. The SRR is located
      -696 to -521 bp upstream of the transcription start site; it is modular in nature
      and can confer steroid responsiveness to a heterologous promoter (ADH1) linked to
      a GFP reporter gene. In vitro DNase I protection analyses of SRR revealed two
      progesterone responsive sequences (-628 to -594 and -683 to -648) and one beta
      oestradiol responsive sequence (-628 to -577), which was further corroborated by
      the gel mobility shift assay. Deletion analyses within the SRR further delimited
      these steroid responsive sequences into two distinct elements, viz. SRE1 and
      SRE2. While SRE1 (-677 to -648) responds only to progesterone, SRE2 (-628 to 
      598) responded to both progesterone and beta-oestradiol. Both SRE1 and SRE2 were
      specific for steroids, as they did not respond to other drugs, such as
      cycloheximide, miconazole and terbinafine. In silico comparison of the SRE1/2
      with the promoter sequences of other MDR (CDR2 and PDR5) and non-MDR (HSP90)
      steroid-responsive genes revealed a similarity with respect to conservation of
      three 5 bp stretches (AAGAA, CCGAA and ATTGG). Taken together, we have identified
      a novel steroid responsive cis-regulatory sequence in the CDR1 promoter, which
      presumably can be instrumental in understanding the steroid response cascade in
      Candida albicans.

PMID- 14968429
TI  - Large-scale screening of yeast mutants for sensitivity to the IMP dehydrogenase
      inhibitor 6-azauracil.
AB  - Mutations in several genes encoding components of the RNA polymerase II
      elongation machinery render S. cerevisiae cells sensitive to the drug 6-azauracil
      (6AU), an inhibitor of IMP dehydrogenase and orotidylate decarboxylase. It is
      thought that a reduction in nucleotide levels following drug treatment causes
      transcriptional elongation to be more dependent on a fully functional RNA
      polymerase. To gain insight into the basis of the 6AU-sensitive phenotype and
      discern its specificity, we screened almost 3000 deletion mutants for growth in
      the presence of drug; 42 (1.5%) were reproducibly sensitive to the drug. The
      sensitive mutants included several missing known transcription elongation
      factors, but the majority were in genes involved in other cellular processes. Not
      all of the 6AU-sensitive strains displayed cross-sensitivity to mycophenolic acid
      (MPA), another drug that inhibits IMP dehydrogenase and has been employed as a
      screening agent for elongation mutants, showing that these two drugs are
      mechanistically distinct. Several of the mutants were tested for the ability to
      induce transcription of IMP dehydrogenase-encoding genes, in response to 6-AU and
      MPA treatment. As expected, mutants defective in transcriptional elongation
      factors were unable to fully induce IMPDH expression. However, most of the 6AU
      sensitive strains had normal levels of IMPDH expression. Thus, although 6AU
      sensitivity often results from defects in the elongation machinery, mutations
      that compromise processes other than transcription and induction of IMPDH also
      lead to sensitivity to this drug.

PMID- 14968430
TI  - Overexpression of ovine leptin in Pichia pastoris: physiological yeast response
      to leptin production and characterization of the recombinant hormone.
AB  - Ovine leptin was cloned in the methylotrophic yeast Pichia pastoris using a
      pPIC9K vector. Leptin was produced and secreted into the culture medium using the
      Saccharomyces cerevisiae alpha-mating factor prepro signal by five clones.
      Expression levels of leptin varied from clone to clone, depending on the copy
      number of the ob gene. Highest expression was observed with the single-copy clone
      S27 (250 mg/l). The modifications of culture conditions in batch and fed-batch
      culture increase the yield of protein. The use of higher cell concentration (63
      g/l) before induction of oLept associate with a regulation of pH at 3.2, which
      decreases the effects of proteolysis, increases the expression level of the oLept
      to 402 mg/l. Moreover, compared with the non-producer clone, we observed a
      drastic decrease in growth rate and biomass yield in the leptin-producing clones.
      At the end of the fed-batch phase at pH 3.2 with clone S27, mortality rate
      reached 17.3%. Results showed that recombinant leptin production induced
      metabolic stress, and a negative impact on biomass yield and growth rate. We
      characterized the recombinant leptin produced by clone S27. It exhibited a
      molecular mass of 16 kDa, an N-terminal amino acid sequence identical to that of
      ovine leptin but with an additional tyrosine introduced by the cloning site.
      Moreover, it was found to be biologically active in vitro. The available
      production of a large quantity of oLept will strengthen the functional study for
      theoretical and practical purposes.

PMID- 14968431
TI  - The role of Ynt1 in nitrate and nitrite transport in the yeast Hansenula
      polymorpha.
AB  - Ynt1 is the only high-affinity nitrate uptake system in Hansenula polymorpha.
      Nitrate uptake was directly correlated with the Ynt1 levels and shown to be
      independent of nitrate reductase (NR) activity levels. Ynt1 failed to transport
      chlorate and, as a result, strains lacking YNT1 were sensitive to chlorate, as is
      the wild-type. Nitrite uptake in a wild-type strain was partially inhibited by
      nitrate to levels shown by a YNT1-disrupted strain in which, in turn, nitrite
      transport was not inhibited by nitrate. It is concluded that nitrite uptake takes
      place by two different transport systems: Ynt1 and a nitrite-specific
      transporter(s). The nitrite-specific transport system was induced by nitrate;
      consistently, no induction was observed in strains lacking the transcription
      factor YNA1, which is involved in nitrate and nitrite induction of the nitrate
      assimilatory structural genes. Ynt1 presents its optimal rate for nitrite uptake
      at pH 6, while pH 4 was optimal for the specific nitrite uptake system(s). At pH
      5.5, the contribution of Ynt1 to high-affinity nitrate and nitrite uptake was
      around 95% and 60%, respectively. The apparent Km of Ynt1 for nitrate and nitrite
      is in the microM range, as is the specific nitrite uptake system for nitrite. The
      analysis of the effect of the reduced nitrogen sources on nitrate assimilation
      revealed that glutamine inactivates nitrate and nitrite transport, dependent on
      Ynt1, but not the nitrite-specific system.

PMID- 14968432
TI  - Molecular characterization of the commonly used human androgen receptor
      expression vector, pSG5-AR.
AB  - BACKGROUND: pSG5-AR is a commonly used androgen receptor (AR) expression vector.
      However, a detailed molecular characterization of this construct has not been
      published. In this study, we describe the molecular organization of the above
      plasmid and analyze the AR transcript coded by the above construct. METHODS: pSG5
      AR was sequenced by the standard dideoxy sequencing method. The obtained sequence
      was analyzed by the DS Gene software. RESULTS: A molecular map of the pSG5-AR
      plasmid as well as a map of the AR insert is provided. The AR transcript from
      pSG5-AR is lacking significant portions of the 5'- and 3'-untranslated region
      (UTR) and contains shorter than average CAG and GGC repeats. CONCLUSIONS: The
      above characteristics of the pSG5-AR are significant and may result in different
      regulation pattern of expression of the expressed AR in comparison to the
      endogenous gene. Such a conclusion is based on the knowledge that post
      transcriptional regulation plays an important role in controlling the levels of
      AR in a cell. Such regulation is controlled by the regulatory elements within the
      5'- and 3'-UTRs of the AR transcript. In addition, this vector might be coding
      for an AR with a different transactivational capacity than the endogenous AR
      gene. The transactivational activity of AR was shown to be affected by the size
      of the trinucleotide-repeat-regions (CAG and GGC) within the gene.

PMID- 14968433
TI  - The novel Ras antagonist, farnesylthiosalicylate, suppresses growth of prostate
      cancer in vitro.
AB  - BACKGROUND: The majority of men with advanced prostate cancer (PCa) respond to
      androgen deprivation therapy (ADT) with objective evidence of tumor regression.
      However, these tumors will regrow in the presence of low-androgen levels after 12
      18 months. Regrowth after ADT is associated with upregulation of growth factor
      (GF) mediated pathways. The compound farnesylthiosalicylate (FTS), a specific
      antagonist of the 21 kDa Ras protein, suppresses GF signaling and it might be a
      useful therapy against advanced PCa. METHODS: We measured androgen and GF
      dependent growth of androgen dependent LNCaP and androgen hypersensitive CWR-R1
      PCa cells in response to specific inhibitors of GF pathways, including FTS.
      Inhibition of GF mediated signaling and cell-cycle pathways was confirmed by
      Western blotting of extracts from treated cells. RESULTS: Both LNCaP and CWR-R1
      cells were dependent on GF signaling pathways for cell growth. FTS, as well as
      suppressing cell growth, inhibited GF signaling pathway activity and reduced the
      levels of E2F1, p-Rb, and p-cdc2, all GF dependent mediators of cell-cycle
      progression. CONCLUSIONS: These data suggest that FTS might be a useful agent
      against PCa that has relapsed after ADT.

PMID- 14968434
TI  - Differential expression of cell cycle regulatory molecules and evidence for a
      "cyclin switch" during progression of prostate cancer.
AB  - BACKGROUND: Deregulation of the cell cycle can be viewed as both cause and
      consequence of cancer. Cyclin expression regulates progression through the cell
      cycle and although some cyclins have been examined in prostate cancer, the
      spatial and temporal changes in expression of these molecules during progression
      of autochthonous disease has not been fully explored. METHODS: Expression
      patterns of cyclins and cyclin dependent kinases during the different stages of
      progression in the spontaneous autochthonous TRAMP model were examined by RNAse
      protection assay, Western blot analysis, and immunohistochemistry. RESULTS:
      Differential expression of cell cycle regulatory molecules was observed during
      prostate cancer progression. Levels of the D-type cyclins decreased during
      progression while expression of cyclin E increased both at the mRNA and protein
      levels. The level of cyclin A and cyclin B expression increased beginning in
      early stage tumors and continued to increase throughout progression. The levels
      of cyclin dependent kinases did not change substantially during progression of
      the TRAMP model. CONCLUSIONS: The spatial and temporal pattern of mitotic cyclin
      expression during prostate cancer progression suggests that these molecules
      represent potential therapeutic targets. The differential expression of D-type
      cyclins may have implications with respect to androgen receptor mediated gene
      expression.

PMID- 14968435
TI  - Separation of enzymatically active and inactive prostate-specific antigen (PSA)
      by peptide affinity chromatography.
AB  - BACKGROUND: Prostate-specific antigen (PSA) is a serine protease with highly
      prostate-specific expression and an important marker for prostate cancer. We have
      previously identified novel PSA-binding peptides that enhance the enzymatic
      activity of PSA when produced as fusion proteins. METHOD: PSA-binding peptides
      and derivatives with a spacer were chemically synthesized and used to prepare an
      affinity column, which was used to fractionate PSA in seminal plasma, serum, and
      LNCap cell culture medium. RESULTS: Approximately 67% of seminal plasma PSA bound
      to the peptide affinity column and was eluted under mild conditions. Eluted PSA
      was intact and enzymatically active while the unbound fraction mainly contained
      various nicked forms. ProPSA from LNCap cells bound to the peptide column only
      after activation by trypsin. CONCLUSIONS: PSA-binding peptides can be used to
      separate enzymatically active and inactive forms of PSA. Thus the peptides are
      potentially useful as ligands for development of methods for specific detection
      of active free PSA.

PMID- 14968436
TI  - A prospective longitudinal study comparing the impact of external radiation
      therapy with radical prostatectomy on health related quality of life (HRQOL) in
      prostate cancer patients.
AB  - BACKGROUND: The objective of the present study is to compare the impact on the
      general and disease-specific health related quality of life (HRQOL) of external
      radiation therapy (ERT) with radical prostatectomy (RP) in patients with
      localized prostate cancer, and to explore which factors, and to what extent,
      contribute to the assessed changes in HRQOL. METHODS: One hundred and thirty
      eight patients participated in this prospective longitudinal study. They
      completed before treatment (T0) and after 12 months (T1) a questionnaire
      constructed of validated instruments, measuring HRQOL and several psychosocial
      factors (PF). Among other things, multiple regression analyses including all
      baseline characteristics, HRQOL and PF were executed in order to meet the
      objectives. RESULTS: RP patients showed significantly more improvement in their
      emotional function, while they reported more incontinence and a worse sexual
      function. There was significantly more improvement in the overall HRQOL of ERT
      patients, while the changes in the gastrointestinal function of these patients
      were significantly worse. Only the differences with respect to incontinence can
      be attributed to the treatment itself. Almost all HRQOL change scores are
      primarily influenced by their own baseline score. The influence of other factors,
      like age, socioeconomic status, and several PF, is limited. CONCLUSIONS: The
      impact on HRQOL of ERT is similar to that of RP, except for incontinence. RP
      patients suffer more from incontinence than ERT patients. Changes in the assessed
      HRQOL are mainly influenced by the pre-treatment HRQOL scores.

PMID- 14968437
TI  - Effects of transforming growth factor-beta1 on parathyroid hormone-related
      protein mRNA expression and protein secretion in canine prostate epithelial,
      stromal, and carcinoma cells.
AB  - BACKGROUND: Bone metastases of prostate carcinoma are associated with
      osteoblastic metastases. Tumor-derived factors, such as parathyroid hormone
      related protein (PTHrP), may promote the development of osteoblastic metastases.
      We examined the effect of transforming growth factor-beta1 (TGF beta 1) on PTHrP
      mRNA expression and PTHrP secretion in normal canine prostate epithelial cells
      (PEC) and stromal cells (PSC), and in canine prostate carcinoma cells (PCC).
      METHODS: Primary cultures of PEC, PSC, and PCC were produced. The effect of TGF
      beta 1 on PTHrP mRNA expression was measured by Northern blot, and secretion of
      PTHrP into culture medium was measured by immunoradiometric assay (IRMA).
      Degradation of recombinant-human PTHrP (rhPTHrP) (1-84) inoculated in prostate
      cell cultures was measured over 24 hr. Arginine esterase (AE) activity in tissue
      and conditioned medium was also measured. RESULTS: TGF beta 1 increased PTHrP
      mRNA expression in a time- and dose-dependent manner in PEC and in PCC. TGF beta
      1 decreased PTHrP mRNA in PSC. TGF beta 1 significantly increased PTHrP secretion
      (P < or = 0.05) into PEC but not PSC conditioned medium. rhPTHrP was
      significantly (P < or = 0.05) degraded in PEC conditioned medium as compared to
      PSC conditioned medium. AE activity was present in prostate and prostate
      carcinoma tissue, but not in conditioned medium from PEC or PSC. CONCLUSIONS: TGF
      beta 1 increased PTHrP mRNA expression in canine PEC and PCC, and decreased
      expression in PSC. This regulatory pathway may be important in the pathogenesis
      of osteoblastic metastases.

PMID- 14968438
TI  - Differential expression of hZnT-4 in human prostate tissues.
AB  - BACKGROUND: Altered zinc levels in prostate benign prostatic hyperplasia (BPH)
      and carcinoma is well documented. It is not known whether loss of zinc, necessary
      to restrain aggressive growth, results from loss of a single specific or multiple
      zinc transporters. METHODS: Human prostate tissues from patients who underwent
      radical prostatectomy were screened by RT-PCR analysis for five zinc
      transporters. Relative cDNA expression was determined in normal, BPH, and tumor
      specimens and four prostate epithelial cell lines. RESULTS: Surgical specimens
      were obtained from patients with assigned Gleason scores ranging from 5 to 9.
      Relative expression of hZIP-1 and hZnT-1 were prominent in most samples with
      relatively lesser degree of expression of hZIP-2 and no detectable expression of
      hZnT-3. Expression of hZnT-4 was decreased in BPH and tumor samples compared to
      normal tissue. CONCLUSIONS: These data suggest that zinc homeostasis in normal
      prostate tissues results from an interplay of multiple transporters and decreased
      hZnT-4 expression is associated with prostate tissue abnormalities independent of
      total cellular zinc content.

PMID- 14968439
TI  - The ceramide analog, B13, induces apoptosis in prostate cancer cell lines and
      inhibits tumor growth in prostate cancer xenografts.
AB  - BACKGROUND: Apoptosis is a therapeutic target for the elimination of cancer
      cells. As elevations in ceramide levels induce apoptosis, there is much
      excitement about the use of agents that elevate ceramide levels as novel
      chemotherapeutic agents. Ceramidases are enzymes involved in degradation of
      ceramide and inhibition of ceramidase has been proposed as a mechanism to
      increase ceramide levels. This study provides the first insight into the effect
      of B13, an inhibitor of acid ceramidase, on human prostate cancer cell lines and
      xenografts. METHODS: Cell death was evaluated by the trypan blue assay; apoptosis
      by the Apo2.7 apoptosis assay; and glutathione levels by HPLC. Tumors were
      irradiated with a dose of 5 Gy of X-rays (250 kVp, 15 mA, 2 Gy/min) and tumor
      volume was measured during the course of the experiment. At the conclusion of the
      experiment, tumor weight was determined and the tumors were evaluated
      histologically. RESULTS: B13 is an inducer of cell death, by apoptosis, in
      cultured prostate cancer cells. LNCaP and PC3 cells have different responsiveness
      to the enantiomers of B13. In LNCaP cells, the R enantiomer of B13 (10 microM)
      was significantly more effective than the S enantiomer at inducing cell death as
      determined by the trypan blue assay, culminating in approximately 90% cell death
      at 48 hr. In contrast, the same concentration of B13S induced <20% cell death at
      48 hr. In PC3 cells, the S enantiomer was a more effective inducer of cell death,
      culminating in approximately 30% cell death, relative to 14% for B13R in this
      model. Evaluation of induction of apoptosis by the Apo2.7 mitochondrial assay
      confirmed that this induction of cell death was by apoptosis. Concurrent with
      induction of apoptosis, glutathione levels drop in response to B13. Specifically,
      B13R caused a significant drop in glutathione levels in LNCaP cells, culminating
      in a reduction to 40% control values at 48 hr. In PC3 cells, in contrast, the
      drop in glutathione levels was more dramatic, culminating in a drop to 12%
      control values in response to B13S at 48 hr. The effects of B13R, however, were
      not significantly different from control values. In in vivo studies using a model
      of xenografted androgen-insensitive prostate cancer, B13 sensitized the tumors to
      the effects of radiation, resulting in a significant reduction in tumor volume
      and weight after treatment with the combination of B13 and radiation. Microscopic
      evaluation of the tumors indicated that apoptosis was the primary mechanism of
      this effect. CONCLUSIONS: Targeting ceramide pathways may be a novel treatment
      strategy for hormone refractory prostate cancer.

PMID- 14968440
TI  - Cell specific expression of CD10/neutral endopeptidase 24.11 gene in human
      prostatic tissue and cells.
AB  - BACKGROUND: Neutral endopeptidase (NEP/CD10) is a cell surface zinc
      metalloproteinase that functions as part of a regulatory loop controlling local
      concentrations of peptide substrates and associated peptide-mediated signal
      transduction processes. In contrast to the encouraging data dealing with NEP
      activity and regulation in prostate epithelial cells, only a few studies are
      available on the cellular expression and localization of neutral endopeptidase in
      the prostatic stromal and cancer cells. Here, we describe the cellular
      localization of NEP in human prostatic tissue and cells using in situ RT-PCR as a
      novel molecular biological approach. METHODS: Immunofluorescence and Western blot
      experiments were performed to control the expression and distribution of the NEP
      in normal and malignant human prostatic tissues and cell lines. NEP gene
      expression was monitored by RT-PCR, NEP mRNA was detected in paraffin tissue
      sections and cultured cells of human prostate by the highly sensitive method of
      one step-in situ reverse transcriptase-polymerase chain reaction (RT-PCR).
      RESULTS: NEP mRNA was detected in human prostatic tissue and in cultured cells by
      means of in situ RT-PCR. Prostatic tissue showed strong signals in the glandular
      epithelium and weak signals in the stroma, cultured cells displayed strong
      signals in prostate cancer cells (LNCaP) and weak signals in stromal cells
      (hPCPs). Western blot experiments were performed using whole cell extracts to
      proof the presence of NEP protein in LNCaP and hPCPs. The experiments confirm the
      expression of NEP by both cell types, however, the experiment with hPCPs cells
      showed two bands. NEP-immunofluorescence was strong in normal prostatic
      epithelium and confined to the apical plasma membrane. In dedifferentiated
      prostate cancer specimens, immunofluorescence of apical plasma membranes was
      lost, and both the cytoplasm and portions of the plasma membrane were
      immunoreactive for NEP. Prostate cancer cells (LNCaP) showed a strong
      immunoreaction of the plasma membrane and the cytoplasm. In comparison with LNCaP
      cells, only a weak cytoplasmic immunofluorescence was found in some stromal cells
      (hPCPs). CONCLUSIONS: In normal prostatic tissue and specimens derived from human
      prostate cancer, NEP mRNA and protein are expressed mainly by the epithelial
      cells and to a minor extent by the stromal cells of human prostate glands. In
      situ RT-PCR is a powerful and straightforward approach for the routine and rapid
      detection of cellular specific expression of low copy genes.

PMID- 14968441
TI  - Intraosseous growth of human prostate cancer in implanted adult human bone:
      relationship of prostate cancer cells to osteoclasts in osteoblastic metastatic
      lesions.
AB  - BACKGROUND: More than 80% of patients with advanced prostate cancer have skeletal
      involvement, but the biology of bone metastasis is poorly understood. This study
      investigated the in vivo formation and progression of bone metastases under
      conditions that resembled the human bone environment as closely as possible.
      METHODS: Adult human bone fragments were implanted subcutaneously into 120 male
      NOD/SCID mice. Four weeks later, 1 x 10(7) LNCaP prostate cancer cells or
      phosphate-buffered saline were injected intravenously into 80 or 40 mice,
      respectively. The implanted bone fragments were removed from 20 to 10 mice in
      each group at 2, 4, 6, and 8 weeks after injection. RESULTS: LNCaP colonized the
      bone marrow blood vessels within 2 weeks, and then gradually expanded into the
      entire medullary cavity. An osteoblastic response often occurred at the edges of
      metastatic foci (intertrabecular bone metaplasia). In addition, new bone
      formation was observed adjacent to mature lamellar bone (appositional bone
      formation). These two processes appeared to occur through different mechanisms,
      but might similarly cause osteosclerosis. Osteoclasts showed a marked increase in
      numbers at sites of early tumor invasion, whereas few osteoclasts were observed
      at sites where tumor invasion was complete. CONCLUSIONS: The predominance of
      osteoblastic change with resorption may lead to bone remodeling in metastatic
      lesions, and osteoclasts may play an important role in bone metastasis from
      prostate cancer.

PMID- 14968442
TI  - Metabolic susceptibility genes and prostate cancer risk in a southern European
      population: the role of glutathione S-transferases GSTM1, GSTM3, and GSTT1
      genetic polymorphisms.
AB  - BACKGROUND: Glutathione S-transferase (GST) metabolic enzymes may be involved in
      the development of human cancer. Genetic polymorphisms have been reported in
      GSTM1, GSTM3, and GSTT1 with functional alterations and influencing cancer risk.
      METHODS: We analyzed DNA samples from 335 (670 alleles) unrelated individuals,
      185 community control subjects, and 150 prostate cancer (PC) patients, for GSTM1,
      GSTM3, and GSTT1 genotypes using polymerase chain reaction (PCR). RESULTS: The
      analysis of the frequencies from the 670 alleles indicates that men carrying two
      B-alleles (GSTM3) have increased risk for PC (OR = 5.50, 95% confidence interval
      (CI) 1.2-25.8; P = 0.016). Multivariate logistic regression analysis confirmed
      this association (OR = 5.2, 95% CI 1.1-25.0; P = 0.036). No increased PC risk was
      observed for men carrying any of the GSTM1 or GSTT1 genotypes (OR = 1.20, 95% CI
      0.75-1.90; P = 0.420 for GSTM1 null and OR = 0.87, 95% CI 0.50-1.51; P = 0.550
      for GSTM1 null). However, GSTT1 null was overrepresented in men with advanced PC
      disease (P = 0.038). CONCLUSIONS: Our results indicate that polymorphism in the
      GSTM3 may be an important biomarker for PC risk, especially in the definition of
      the genetic risk profile of populations of southern Europe.

PMID- 14968443
TI  - Clinical understaging in patients with prostate adenocarcinoma submitted to
      radical prostatectomy: predictive value of serum chromogranin A.
AB  - PURPOSE: To evaluate whether the pretreatment determination of serum chromogranin
      A (CgA) can provide information beyond that obtained with serum prostate specific
      antigen (PSA) and Gleason score at biopsy as a predictive factor of clinical
      understaging (T2-pT3) of prostate adenocarcinoma. MATERIALS: In this prospective
      study, we analyzed 83 consecutive patients with clinical T2N0M0 prostate
      adenocarcinoma submitted to radical prostatectomy (RRP). On the same day of RRP,
      before surgery, a blood sample for the determination of serum total PSA and CgA
      levels (RIA) was obtained. RESULTS: After RRP, 27 of the 83 cases (32.5%) showed
      extracapsular disease extension (pT3) at the final pathological examination and
      were considered clinically understaged. A significant association between serum
      CgA and pathological stage (r = 0.3830; P = 0.0004) was found. At the
      multivariate analysis, serum CgA and PSA, but not biopsy Gleason score, were
      found to be significant pretreatment independent predictors of pT3 at RRP (P =
      0.00004 and P = 0.0018, respectively). The relative risk of clinical understaging
      significantly varied according to serum CgA levels. Using a CgA cut-off value of
      60 ng/ml, PPV and NPV for clinical understaging were 0.5161 and 0.7885,
      respectively (P = 0.0072). CONCLUSIONS: Serum CgA could be incorporated into risk
      assessment models of newly diagnosed prostate cancer.

PMID- 14968444
TI  - Mostar University Medical School, Bosnia and Herzegovina: first graduates.

PMID- 14968445
TI  - Educatione ad excelentiam: role of scientific journals in galvanizing mental
      health research in low- and middle-income countries.

PMID- 14968446
TI  - What can be learned from impact factor of Croatian Medical Journal, 1994-2003?
AB  - We calculated the impact factor (IF) of the Croatian Medical Journal (CMJ) for
      the 1994-2003 period, ie, including the years before its inclusion into the
      Institute of Scientific Information (ISI) database in 1999. There was a latency
      period of several years from the inclusion of the Journal in indexing databases
      to the IF increase. According to the ISI Journal of Citation Report, IF of the
      CMJ in 2001 and 2002, was 0.43 and 0.71 and journal was ranked 70 and 56,
      respectively, out of 107 journals under the category "Medicine, general and
      internal". The analysis of distribution and type of citations that contributed to
      the IF of the CMJ revealed that its increase mainly resulted from the increase in
      the number of fully independent citations and author auto-citations in journals
      other than CMJ. The factors that probably accounted for the IF increase were
      better international visibility, full-text free-of-charge online availability,
      and large number of international contributions, especially in some thematic
      issues.

PMID- 14968447
TI  - Importance of object relations theories for development of capacity for mature
      love.
AB  - We discuss Klein's, Winnicott's, and Mahler's object relational theories relevant
      for creating and maintaining the mature love relationship. The concept of love
      refers to the basic human relationship. The capacity for adult love involves the
      attainment of the relation towards the object as whole, satisfying the emotional
      needs of the self, including simultaneous tolerance of the specific needs of the
      object. It also involves the optimum resolution of anxiety related to schizo
      paranoid and depressive positions and phases of separation and individuation.
      Primitive defense mechanisms, such as splitting, are replaced by more mature
      defense mechanisms, and primitive idealization is replaced by more mature
      idealization. The fusion with the object is reversible and helps in creating the
      experience of closeness with the partner, while the possibility of separation
      provides the possibility of recognizing and respecting the differences. Obstacles
      in the development of object relationships from pre-object to object phase, from
      symbiotic to separation and individuation phase can impair the capacity to love.

PMID- 14968448
TI  - Views on sexuality in croatian medieval sources.
AB  - We analyzed attitudes towards sexuality during the medieval period in Croatia.
      For that purpose we investigated numerous medical and literary texts, statutes,
      and specific natural philosophical work entitled "Lucidar". Contrary to medical
      books, which had a low impact on the broader community, literary texts were
      important in spreading messages on sexuality, as well as in shaping medieval
      mentality and creating sexual taboos. Consequently, a specific perspective and
      culture influenced rules and practices for community protection, as well as
      various levels of social systems. Within the three large groups of sources, we
      selected those typical both in their content (ideas) and forms, and
      representative in shaping attitudes toward sexuality on our territory. The first
      group of sources (examples from literary genres) were identified as an important
      vehicle in transferring messages of morality, moral obligation and sexuality in
      general. Deeply rooted in Christianity they became a pattern according to which
      the way of life and value were measured, a specific view toward sexuality was
      shaped, and notions of stigma and taboo articulated.

PMID- 14968449
TI  - Reform of medical education in Bosnia-Herzegovina: luxury or necessity?
AB  - We present the current status of medical education in Bosnia-Herzegovina to set
      the stage for the curriculum reform. Two principal questions are asked: is the
      reform necessary, and is it possible? In spite of the differences in size and
      tradition of medical schools in Bosnia and Herzegovina (BH), they have more
      features in common than not: all of them are under internal and external
      pressures for change and reform, which will eventually be inevitable. The history
      and strategy of reform in Heidelberg, Germany, and Vienna, Austria, are described
      and recommendations are made on the basis of their experience. The consensus on
      the need for reforms has to be reached by all parties involved, ie, faculty,
      administration, students, and the medical community. After that, the reform
      process must proceed according to the agreed timetable. The job should be
      delegated to a dedicated task force and work coordinated through the ongoing
      "Dictum" project, directed exclusively at reform of medical curricula in BH. The
      project is funded by a European Union TEMPUS program.

PMID- 14968450
TI  - Breastfeeding practices in Mostar, Bosnia and Herzegovina: cross-sectional self
      report study.
AB  - AIM: To investigate breastfeeding practices among mothers of infants in the city
      of Mostar, Bosnia and Herzegovina. METHODS: The cross-sectional self-report study
      was conducted among 326 mothers of infants visiting the Advisory Center for
      Infants at the Medical Center in Mostar and at the Children's Department of
      Mostar University Hospital between January and May 2003. The data were collected
      from mothers by trained interviewers using a structured interview. In addition to
      demographic data, mothers were inquired about the frequency of breastfeeding, use
      of commercial infant food products, and the reasons for the termination of
      breastfeeding. RESULTS: According to mothers' statements, 85%, 70%, 44%, and 8%
      infants were breastfed at the age of 1, 3, 6, and 12 months, respectively.
      Significantly more infants aged < or =3 months were breast feed than not. Infant
      formula was given to 31%, 43%, 85%, and 62% of infants aged 1, 3, 6, and 12
      months, respectively. Cow milk was given to 19% of 6-month-old infants, and the
      proportion of infants fed with cow milk increased with age. Tea and water were
      often added to the infant diet. The most frequently stated reason for the
      termination of breastfeeding was the lack of breast milk. Decision whether to
      breast feed or not was made by the mothers themselves, in 85% of cases before the
      delivery. Only 27% of mothers received advice on breastfeeding from the medical
      personnel. CONCLUSION: The number of breastfed infants decreased with their age,
      especially after 3 months of age. Infant formulas and cow milk were introduced
      into infant diet very early. The reasons stated for the termination of
      breastfeeding reflected unawareness of the indications for ablactation and
      advantages of breastfeeding. Young mothers should be better educated on
      breastfeeding.

PMID- 14968451
TI  - What do young people from Mostar, Bosnia and Herzegovina know about contraception
      and sexual health?
AB  - AIM: To determine the knowledge of adolescents living in Mostar, Bosnia and
      Herzegovina, about contraception and sexual health. METHODS: We used an anonymous
      questionnaire to survey a random sample of 120 high school students, 60 from two
      general high schools and 60 from a vocational school. There were 30 male and 30
      female students aged 15-17 years from each type of school. The questionnaire
      consisted of 24 questions: 17 tested the students' knowledge on the menstrual
      cycle, contraception, emergency contraception, and sexually transmitted diseases
      (STDs), and six inquired how they obtained the information on these issues.
      Student t-test was used to test for score differences between male and female
      students, and between general high school and vocational school students in their
      general and specific knowledge. Pearson's r coefficient was used to test the
      correlation between average grades and knowledge. RESULTS: Female students had
      greater general knowledge (t=3.69, df=118, p<0.001), knowledge on contraception
      (t=3.66, df=118, p<0.001), and knowledge on STDs (t=2.71, df=118, p=0.008) than
      their male peers. General high school students also had greater general knowledge
      (t=2.44, df=118, p=0.016), and knowledge on contraception (t=2.18, df=118,
      p=0.031) or STDs (t=2.36, df=118, p=0.020) than their vocational school peers.
      Major sources of information were magazines (69%), TV/radio (50%), school (37%),
      and friends (36%). The most common reason that kept our examinees from obtaining
      information on these issues was shame (52%). The two most common contraception
      methods known to them were a condom (82%) and contraception pill (77%), whereas
      17% of all students were unfamiliar with any contraception method. When asked
      what could be done to improve their knowledge on sexuality, contraception, and
      STDs, most students opted for the inclusion of sexual education into the school
      curricula. CONCLUSION: Female students knew more about contraception and sexual
      health than their male peers. Young people should be provided with more
      information on sexual health.

PMID- 14968452
TI  - Characteristics of venomous snakebites in Herzegovina.
AB  - AIM: To investigate the degree to which primary and secondary care physicians in
      the Herzegovina region follow the protocols recommended in the literature for
      treatment of patients bitten by a venomous snake. METHOD: We retrospectively
      examined hospital records of all patients treated at the Department of Infectious
      Diseases, Mostar University Hospital, for intoxication following a venomous
      snakebite in the 1997-2002 period. The data on demographic characteristics,
      clinical presentation, therapy protocols, and final outcome were collected for
      each patient. RESULTS: From 1997 to 2002, 43 men (60.5%) and 28 women (33.4%)
      were treated at our Department for a venomous snakebite. The greatest number of
      snakebites occurred in persons older than 60 (chi-square=12.44, df=3, p=0.006)
      and during the summer months (chi-square=8.12, df=1, p=0.004). More than half of
      the patients (38, or 53.5%) were bitten on the hand. The commonest symptoms and
      signs of the local envenomation were pain (97.1%) and swelling (87.3%), whereas
      general symptoms were tachycardia (39.4%), nausea (33.8%), and vomiting (28.1%).
      Also, 56 patients (78.8%) experienced anxiety and fear. The primary care protocol
      recommended in the literature (antibiotics, tetanus antitoxin, snakebite
      antiserum, and immobilization) was given to only 2 patients (2%). However, there
      were no lethal outcomes. CONCLUSION: Development of a precise evidence-based
      protocol for prehospital management of venomous snakebite is needed in the
      Herzegovina region, followed by educational efforts targeted at primary care
      physicians.

PMID- 14968453
TI  - Were today's professors good students? Case study of the Zagreb University School
      of Medicine.
AB  - AIM: To determine whether the medical school grades of today's professors at the
      Zagreb University School of Medicine could serve as the predictors of their
      subsequent academic success. METHODS: We performed a retrospective descriptive
      study of medical school grades of professors and/or assistant professors at the
      Zagreb University School of Medicine from 1990 to 2003. The professors were
      divided into four groups according to the course they taught: Basic Science,
      Clinical Non-Surgery, Clinical Surgery, and Public Health. In total, data for 297
      professors were analyzed. RESULTS: Today's professors were above-average
      students. The analysis of grades of professors teaching different disciplines
      revealed that Basic Science professors were the best students, followed by Non
      Surgery and Surgery professors, whereas Public Health professors were the worst.
      Grades that professors earned in Public Health courses were the highest, followed
      by grades in Non-Surgical and Surgical courses. The grades in Basic Science
      courses were the lowest. CONCLUSION: Professors at the Zagreb University School
      of Medicine were above-average students and their grades seem to be important
      predictors of future success in academic career. Among today's professors, Basic
      Science professors were the best students.

PMID- 14968454
TI  - Academic profile of students who transferred to Zagreb School of Medicine from
      other medical schools in Croatia.
AB  - AIM: To assess the academic performance of students who transferred to the Zagreb
      School of Medicine from other three medical schools in Croatia. METHODS: Academic
      performance of medical students who moved from Rijeka, Osijek, or Split
      University Medical Schools to the Zagreb University School of Medicine at the
      second or third year was compared with academic performance of students enrolled
      at the Zagreb University School of Medicine. Using the Zagreb Medical School's
      registry, we made a list of 57 transfer students to Zagreb Medical School in the
      1985-1994 period. Control group was formed of students enrolled at the Zagreb
      School of Medicine in the same period, whose names followed in alphabetical order
      after the names of transfer students. Students' performance was analyzed
      according to their grade average before transfer, grade average in the first year
      after transfer, total grade average after transfer, overall grade average, and
      duration of studies. We also analyzed the proportion of students in each group
      who did not pass the admission test at the Zagreb School of Medicine in the year
      before the enrollment in Zagreb, Osijek, Rijeka, and Split Medical Schools.
      Nineteen transfer students, transferred between 1985 and 1988, and their controls
      were excluded from the analysis because of incomplete data. RESULTS: Transfer
      students had significantly lower grade average before transfer (3.2-/+0.6 vs 3.5
      /+0.7, p=0.03, Student t-test), lower grade average in the first year after
      transfer (3.2-/+0.6 vs 3.5-/+0.7, p=0.03), lower total grade average after
      transfer (3.6-/+0.5 vs 4.0-/+0.6, p<0.001), and lower overall grade average (3.5
      /+0.5 vs 3.9-/+0.6, p<0.001) than control students. Median time to graduate for
      transfer students was 7 years (range, 5-9) and 6 years (range, 5-9) for control
      students (p=0.375, Mann-Whitney test). There were significantly more students
      among transfer students who did not pass the admission test at the Zagreb School
      of Medicine in the year before the final enrollment than their controls (15/38 vs
      4/38, p=0.009, chi-square test). CONCLUSION: Transfer students had poorer
      academic performance than students who passed the admission test and were
      enrolled at the Zagreb School of Medicine from the first year of studies.

PMID- 14968455
TI  - Medical students' opinions on physicians' strike: cross sectional questionnaire
      study.
AB  - AIM: To investigate what Zagreb Medical School students think about general
      physicians' strike in Croatia, which began in February 2003. METHODS: We surveyed
      771 students using a specially designed anonymous self-report questionnaire. In
      addition to questions on demographic data (student's sex, year of studies,
      average grade, and whether at least one parent was a physician), the
      questionnaire contained 19 items divided in three subscales, each assessing
      different aspects of student opinion on the strike. The first subscale,
      "Support", assessed students' opinion on situations where strike was an
      acceptable solution (8 items, alpha=0.82). The second one was "Consequences",
      assessing students' opinion on possible negative consequences of physician's
      strike (8 items, alpha=0.77). The third subscale, "Croatia", assessed students'
      opinions about the social and economic status of physicians in Croatia (3 items,
      alpha=0.73). Items were graded on a 5-point Likert-type scale. Data were analyzed
      with nonparametric statistics (Mann-Whitney test, Sperman's r), and the
      significance level was set at p<0.05. RESULTS: Students scored high on the
      "Support" subscale (median=34, range=8-40, interquartile range=6;) and were
      undecided on the "Consequences" subscale (median=23, range=8-40, interquartile
      range=8), whereas on the "Croatia" subscale, their scores were low, reflecting
      their poor opinion on the physicians status in Croatia (median=6, range=3-15,
      interquartile range=4). Students in the clinical years, as well as students whose
      one or both parents were physicians, scored higher on the "Support" subscale and
      lower on the "Consequences" and "Croatia" subscales than their colleagues from
      preclinical years or students whose neither parent was a physician (p<0.001 for
      all, Mann-Whitney test). No differences were found according to the students'
      sex, and there was no correlation between average grades and subscale scores.
      CONCLUSION: Zagreb Medical School students supported the physicians' strike and
      were undecided on its negative consequences. They thought that physicians' status
      in Croatia was poor. This trend was more obvious among students in clinical years
      whose one or both parents were physicians.

PMID- 14968456
TI  - What do grades in clinical subjects depend on? Case study of the Zagreb
      University School of Medicine.
AB  - AIM: To investigate the influence of clinical site, student's and preceptor's
      sex, and preceptor's academic rank on grading in eight clinical subjects at the
      Zagreb University School of Medicine between 1999 and 2002. METHODS: We analyzed
      oral exam grades from five fourth-year clinical courses (radiology, oncology,
      nuclear medicine, internal medicine, and psychiatry) and three fifth-year
      clinical courses (surgery; ear, nose and throat diseases (ENT); and pediatrics).
      Internal medicine course also had a written test, common for all students. We
      recorded the clinical site where the exams were taken, clinical subjects, grades,
      number of attempts at passing the exams, student and preceptor gender, and
      preceptor academic rank. Chi-square test was used for data analysis. RESULTS:
      Grades from all clinical subjects but internal medicine course significantly
      differed, depending on clinical site where the exam was taken. There was a
      significant difference in grades from the internal medicine written exam among
      teaching sites. Preceptors with higher academic ranks awarded better grades. Male
      and female students performed equally well. Female preceptors gave significantly
      lower grades, regardless of the student gender and created a higher failure rate.
      CONCLUSION: Oral exams are a subjective method of evaluating students' knowledge
      of clinical subjects and depend on the site of teaching and examination. Written
      exams and structured clinical skills examinations should be implemented for
      objective student assessment.

PMID- 14968457
TI  - Daily caffeine intake among Osijek High School students: questionnaire study.
AB  - AIM: To assess caffeine intake habits of Osijek high school students and identify
      the most important sources of caffeine intake. METHODS: Adjusted Wisconsin
      University Caffeine Consumption Questionnaire was administered to 571 high school
      students (371 boys and 200 girls in the ninth grade) from Osijek, the largest
      town in eastern Croatia. The level of caffeine in soft drinks was determined by
      the high pressure liquid chromatography method, and in chocolate and coffee from
      the literature data. RESULTS: Only 10% of our participants did not use foodstuffs
      containing caffeine. The intake of caffeine originated from soft drinks (50%),
      coffee (37%), and chocolate (13%). The mean caffeine concentration in soft drinks
      was 100-/+26.9 mg/L. The mean estimated caffeine intake was 62.8-/+59.8 mg/day.
      There was no statistically significant difference between boys and girls in
      caffeine consumption (1.0-/+0.9 mg/kg bw for boys vs 1.1-/+1.4 mg/kg bw for
      girls). Daily caffeine intake of 50-100 mg was recorded in 32% of girls and 29%
      of boys, whereas intake greater than 100 mg/day was recorded in 18% of girls and
      25% of boys. CONCLUSION: Soft drinks containing caffeine were the major source of
      caffeine intake in high school students. Large-scale public health measures are
      needed to inform the public on health issues related to excessive intake of
      caffeine-containing foodstuffs by children and adolescents.

PMID- 14968458
TI  - Predictors of smoking behavior of first year university students: questionnaire
      survey.
AB  - AIM: To assess the prevalence of smoking and sociodemographic factors related to
      smoking behavior of first year university students in Adana, Turkey. METHODS: The
      sample was selected from two faculties (Faculty of Engineering and Architecture
      and Faculty of Agriculture) using the method of simple cluster sampling,
      representing the university student population. The students filled out an
      anonymous questionnaire comprising 17 questions related to their sociodemographic
      characteristics and smoking behavior. The response rate was 73.5% (471 out of 640
      students). RESULTS: The prevalence of daily smoking among the first year students
      was 21.4%, with the predominance of men (25.0%) over women (12.9%). Most students
      (89.1%) had positive expectations about quitting smoking in the next 5 years ("I
      will quit smoking", "I will decrease the number of cigarettes I smoke", and "I
      will continue to be a non-smoker"). The smoking behavior was significantly
      related to student's sex (p=0.026, Pearson's chi-square test), mother's education
      (p=0.029, Pearson's chi-square test), number of failed grades (p=0.011, ANOVA),
      student's monthly income (p<0.001, Pearson's chi-square test), and having friends
      who smoke (p<0.0001, Pearson's chi-square test). CONCLUSION: The main
      determinants of regular smoking behavior for university students in Turkey were
      male sex, low academic performance, having smoking friends, high level of income,
      and a mother with high education level. These findings call for making anti
      smoking policies more specific in regard to the targeted population.

PMID- 14968459
TI  - Tobacco use among high shool students in Kampala, Uganda: questionnaire study.
AB  - AIM: To determine the prevalence of tobacco-use and describe tobacco-related
      knowledge, perceptions, and behavior of high school students aged 13-15 years in
      Kampala, Uganda. METHODS: A cross-sectional questionnaire study was carried out
      among 2,789 students in 19 high schools in Kampala District, Uganda, in 2002. In
      each school, three classes from Senior One to Senior Three (average student age,
      13 to 15 years, respectively) were randomly selected. All students who consented
      to participate in the study filled out a questionnaire consisting of 58
      questions, with core items selected from the Global Youth Tobacco Survey. The
      questions were grouped into categories relating to tobacco use, knowledge and
      attitudes toward smoking, exposure to second hand smoke, attitude toward
      cessation of smoking, exposure to tobacco-related advertisements in the media,
      and education on tobacco and smoking in school. RESULTS: Out of 2,789 students,
      488 (17.5%) reported to have smoked tobacco, with 185 (37.9%) of them trying or
      starting smoking before the age of 10. There were 148 (5.3%) current smokers.
      More than two-thirds (77.9%) of current smokers expressed a desire to stop
      smoking, 76.9% had tried to stop, and 84.1% had received help or advice to stop
      smoking. At least two-thirds of the students reported seeing both anti-tobacco
      and pro-tobacco advertisements in the preceding month. About 15.7 % of the
      students had an item with a cigarette brand logo, whereas 11.1% had been offered
      free cigarettes by a tobacco company representative. Current smokers usually
      smoked at home (30.2%), at a friend's place (29.3%), in public places (12.1%), at
      social events (10.4%), and at workplace (1.5%). Current smokers were also more
      likely than non-smokers to be exposed to passive smoking at home (56.4% vs at
      15.9%, respectively; p<0.001). CONCLUSION: Many high school students in Kampala
      are exposed to tobacco advertising, especially through the media. Efforts to
      control smoking in this age-group should also target their parents and other
      family members, by means of the media.

PMID- 14968460
TI  - Attitudes towards premarital testing on human immunodeficiency virus infection
      among Malawians.
AB  - AIM: To determine factors influencing voluntary counseling and premarital testing
      on human immunodeficiency virus (HIV) in Malawi. METHOD: We analyzed the data
      collected by the Malawi Demographic and Health Survey (MDHS) 2000 to determine
      the likelihood of Malawi population to accept HIV testing. The MDHS was a
      nationwide cross-sectional study where cluster sampling technique and an
      interviewer-administered questionnaire were used. We applied the Logit model of
      analysis to determine the HIV testing likelihood according to the following
      parameters: age, place of residence (urban vs. rural), belief that sexual
      abstinence protects from HIV infection, knowledge of a location of HIV testing,
      belief that diagnosis of HIV should be kept secret, and knowledge of anyone with
      AIDS. RESULTS: Out of 3,092 participants, 23.3% lived in urban and 76.7% in rural
      areas. Willingness to have premarital HIV counseling and testing was positively
      associated with increased age, urban residence, and wish to keep one's own HIV
      testing result confidential. However, knowledge of a person with HIV/AIDS, HIV
      testing location, and other sexually transmitted infections/diseases, as well as
      belief that abstinence protects against HIV were inversely related to desire to
      take an HIV test. CONCLUSION: Not all population groups have an equal likelihood
      of accepting voluntary HIV counseling and testing. Public health intervention on
      HIV counseling and testing should be tailored specifically for each population
      group.

PMID- 14968461
TI  - Prevalence and risk factors of substance use among urban adolescents:
      questionnaire study.
AB  - AIM: To examine the prevalence and possible interconnections among the
      frequencies of consuming various psychoactive substances in Zagreb adolescents.
      Also, to assess risk factors associated with the use of tobacco, alcohol, and
      marijuana. METHOD: We applied an anonymous, multi-dimensional, self-reporting
      questionnaire on a representative sample of 2,404 elementary and high school
      students (total age range, 13-23 years) from Zagreb, Croatia. The questionnaire
      was designed to explore the extent to which examinees consumed various
      psychoactive substances, as well as to assess their attitudes and knowledge about
      the substances. The socio-demographic data were collected on all examinees, their
      hierarchy of values, family relations, adjustment to school, relationships with
      peers, and high-risk and delinquent behavior. We analyzed the interconnections
      among the frequencies of consuming various psychoactive substances, and assessed
      the factors possibly predictive of substance use. RESULTS: Almost 90% of all
      examinees experimented with alcohol at least once, 80% with tobacco, 39% with
      marijuana, and 9% with Ecstasy. Thirty-six percent consumed alcohol and 11%
      marijuana several times a month, whereas 28% smoked tobacco daily. Although there
      was no statistically significant difference according to sex in experimenting
      with psychoactive substances, day-to-day abuse was significantly more frequent
      among young men than women. About 43% of our examinees believed consuming
      marijuana should become legally permitted, 37% were against this policy, and 21%
      were undecided on this issue. Our results showed a high degree of interconnection
      among the frequencies of consuming tobacco, alcohol, and marijuana. We also found
      that the best predictive factors for consumption of these three substances were a
      history of high-risk and delinquent behavior, troubled adjustment to school,
      domination of hedonistic values, and poor family relations. Regression analysis
      and pondering for ratios of particular predictors of psychoactive substances use
      gave values for coefficients of multiple regression as follows: R=0.548
      (R(2)=0.300; p<0.001) for tobacco, R=0.575 (R(2)=0.330; p<0.001) for alcohol, and
      R=0.608 (R(2)=0.370; p<0.001) for marijuana. Knowledge about the consequences of
      consuming psychoactive substances positively correlated with the frequency of
      consuming tobacco (r=0.213, p<0.001), alcohol (r=0.226, p<0.001), and marijuana
      (r=0.320, p<0.001). CONCLUSION: Most adolescents had personal experience with
      psychoactive substance abuse, mostly alcohol, tobacco, and marijuana, but only a
      smaller proportion became regular consumers. The frequency of substance
      consumption implied a generalized tendency towards substance abuse among Zagreb
      adolescents. Our findings could serve as empirical basis for the re-evaluation of
      the current drug prevention programs and programs aimed at preventing other forms
      of risk behavior among children and adolescents.

PMID- 14968462
TI  - Teaching disability and rehabilitation medicine at the Medical School in Split,
      Croatia.
AB  - We describe the unsatisfactory situation of teaching disability and
      rehabilitation to medical students, focusing on countries of Central/Eastern
      Europe (CEE), sourcing a selection of relevant literature and reports of
      competent colleagues from these countries. Further, we present a model of
      teaching disability and rehabilitation medicine as it is now taught at the
      Medical School in Split, after the program for teaching Physical Medicine and
      Rehabilitation to the 5th year medical undergraduates was reformed in the
      academic year 2001/2002 to make it a satisfying educational experience that
      focuses on rehabilitation medicine, allowing acquisition of the competence
      necessary for managing persons with disability in the community. In an anonymous
      evaluation questionnaire, 96% of students thought that the new program was very
      good, that it contributed significantly to their general medical education, and
      was useful for their future work as general practitioners. We believe that the
      new program, which is broad in scope and content, well received by students, and
      attains its objectives, deserves to be introduced to a wider medical community.

PMID- 14968463
TI  - An item of good news for medicine in 2004.

PMID- 14968464
TI  - Medicine as a bridge to peace.

PMID- 14968465
TI  - Tragic consequences of inadequate health technology assessment.

PMID- 14968466
TI  - [Neoadjuvant treatment of prostatic cancer].

PMID- 14968467
TI  - [Conn's syndrome: surgical experience].
AB  - BACKGROUND: Primary aldosteronism is a syndrome clinically characterized by
      systemic arterial hypertension and hypokalemia that occurs most frequently as a
      consequence of the excessive production of aldosterone by adrenal cortical
      hyperplasia or a functioning tumor. Surgical resection of the tumor leads to cure
      of the disease in most patients. The aim of this study was to analyze a series of
      patients with an adrenal aldosterone-producing tumor. PATIENTS AND METHODS:
      Clinical records of 13 patients with Conn syndrome were reviewed analyzing the
      clinical presentation, diagnosis, localizing techniques, treatment and follow-up
      with emphasis in the postoperative outcome of hypertension and serum potassium.
      RESULTS: From a total of 105 patients who underwent adrenalectomy in a 12-year
      period (August 1991-February 2003), 13 patients were operated on to remove an
      adrenal aldosterone-producing tumor. Mean age was of 43 +/- 11 years, 8 were
      women and 5 men. All presented with arterial hypertension and 11 also had
      hypokalemia. Diagnosis of Conn syndrome was established by laboratory tests and
      an adrenal tumor was found by image studies in all patients. Open adrenalectomy
      was performed in 2 patients and 11 underwent a laparoscopic procedure. There was
      neither surgical morbidity nor mortality. The histological analysis established
      the diagnosis of adenoma in 12 patients and carcinoma in 1. Mean postoperative
      hospital stay was 3.1 days. A total of 12 patients became normotensive after
      surgery and potassium levels returned to normal in all cases. CONCLUSIONS: Conn
      syndrome was present in 12% of patients undergoing adrenal surgery. Arterial
      hypertension, low plasma renin activity levels, and hypokalemia were present in
      all patients. Image studies were able to localize the tumor in all cases and
      surgical resection of the tumor lead to normal arterial blood pressure in 92% of
      the patients and eukalemia in 100%.

PMID- 14968468
TI  - [Early referral to the nephrologist: impact on initial hospitalization and the
      first 6 months of continuous ambulatory peritoneal dialysis].
AB  - BACKGROUND: The prognosis and outcome in patients with end stage renal disease is
      significantly related to the predialysis care and early or late nephrological
      referral. Late nephrological referral has been associated with more hospital
      admissions and mortality at six months after the dialysis was initiated. We lack
      information about the role of early nephrological referral and its impact in
      biochemical variables and first hospitalization in our country. METHODS: The
      charts of all patients that were admitted to peritoneal dialysis in the period
      01/1999-06/2001 were reviewed. We divided the population in group A with patients
      referred to nephrologist more than 3 months before the start of dialysis (early
      referral) and group B with those patients referred for a period shorter than
      three months or no referred before the start of dialysis (late referral or no
      referral). The patient's characteristics, laboratory values, characteristics of
      the first hospitalization and drugs were analyzed when dialysis was initiated and
      after six months of follow-up. RESULTS: Patients in group A were older and the
      percentage of patients with diabetes and hypertension was higher. The patients
      with early referral started dialysis with higher levels of hemoglobin (9.2 vs.
      8.3 g/dL, p = 0.01) and with lower serum levels of BUN (91 vs. 122.5 mg/dL, p =
      0.0001), creatinine (8.4 vs. 12.8 mg/dL, p = 0.0002) and phosphorus (6.4 vs. 7.7
      mg/dL, p = 0.01). The length of the first hospitalization was shorter in patients
      of Group A (5.7 vs. 10.5 days, p = 0.004) and the emergency department was less
      used to peritoneal catheter placement in this group (46.3 vs. 86.9%, p = 0.01).
      There were not differences in hospitalization between the two groups after six
      months. CONCLUSION: Patients with early referral to a nephrologist show better
      biochemical variables, shorter first hospitalization length and higher percentage
      of elective placement of catheter.

PMID- 14968469
TI  - [Survival, clinical and laboratory characteristics of de novo and secondary
      megakaryoblastic leukemia].
AB  - OBJECTIVE: To describe the frequency and compare the clinical characteristics,
      treatment response, survival and hematologic, immunophenotypic, cytogenetic, and
      histologic findings in adult patients with acute megakaryoblastic leukemia
      (AMegL) and megakaryocytic blast crisis of chronic myeloid leukemia (MegBC-CML).
      MATERIAL AND METHODS: The records of patients with AMegL and MegBC-CML attended
      in our institution between July 1993 and December 2000 were revised.
      Megakaryocytic lineage was established by the presence of one or more
      megakaryocyte/platelet associated antigens (CD41, CD42b, and CD61) in > 20% blast
      cells. RESULTS: In 90 months, 277 patients with acute leukemia were admitted and
      25 with chronic myeloid leukemia (CML) in blast crisis (BC) were identified.
      Twelve of 125 patients (9.6%) with acute myeloid leukemia were AMegL and 32% of
      cases with CML-BC were MegBC-CML. Leukemic cells of patients with AMegL expressed
      more frequently CD15 antigen than blast cells of those with MegBC-CML (83% and
      37.5%; p < 0.05). In contrast, blast cells expressing myeloperoxidase were
      present in 50% and 10% of cases with MegBC-CML and AMegL, respectively (p <
      0.05). Only one patient in each group obtained remission. Although median
      survival in patients with AMegL was lower (70 days) than in those with MegBC-CML
      (175 days) the difference did not reach statistical significance. CONCLUSION:
      AMegL and MegBC-CML differ in some clinical and laboratory characteristics and
      are diseases with poor treatment response and short survival.

PMID- 14968470
TI  - Primary lymphoma of bone.
AB  - Primary lymphoma of bone (PLB) is a rare clinical-pathological entity
      representing less than 1% of all lymphomas. This work was aimed to review the
      presentation characteristics of PLB at the Instituto Nacional de Cancerologia
      including its management and evolution. MATERIAL AND METHODS: Thirty cases of
      lymphoma of bone were diagnosed between 1972 and 1999 from a database including
      577 patients with lymphoma. Among them, only 8 patients (1.36% of the total
      lymphomas) met the criteria set out to be diagnosed as primary lymphoma of bone,
      stage IE. In all patients, diagnosis was histopathologically made through open
      biopsy, and they were classified in accordance with the former criteria of the
      Working Formulation (WF). This review applied the current criteria of the World
      Health Organization (WHO). RESULTS: Three women and five men with a mean age of
      40 years (range 20-65) were identified. Mean physical performance (Karnofsky) was
      80%. Six patients presented clinically evident disease of the affected region.
      The most frequent symptom was pain at the site of the lesion in 3 patients, being
      the cardinal symptom in 1 patient. Histological diagnosis was diffuse large cell
      lymphoma, and B immunophenotype was confirmed in 5 patients. Five patients
      received sequential chemotherapy and radiotherapy; 1 patient received
      chemotherapy; and 2 patients received exclusive radiotherapy. The chemotherapy
      regimes were based on anthracyclines. Five patients presented complete response
      and 3 patients showed progressive disease. One patient showing complete response
      relapse 16 years after the treatment. The mean follow-up in this series was 60
      months (range 3-190 months). Tumor localization and functional condition of the
      patient were the best prognostic factors. Surgery was not therapeutic in any
      case. CONCLUSIONS: PLB still remains a rare clinical-pathological entity, and
      represented 1.3% of total lymphomas in this series. Sequential anthracycline
      based chemotherapy and radiotherapy are the most important therapeutic choices.
      Functional condition of patients at diagnosis and tumor localization were the
      most accurate prognostic factors.

PMID- 14968471
TI  - [Impact of the new criteria for the diagnosis of gestational diabetes on the
      estimate of its prevalence].
AB  - OBJECTIVE: This study was aimed to identify the prevalence of gestational
      diabetes (GD) defined as any glucose intolerance detected in a pregnant women
      using the oral glucose tolerance test (OGTT) protocol, proposed by the World
      Health Organization (WHO) and to explore the effect of late pregnancy on the
      glucose tolerance test. Two groups of pregnant women > 20 years of age were
      evaluated with an OGTT, one group at the beginning, and the other one at the end
      of the third trimester, newborns weight and gestational age were recorded at the
      end of pregnancy. PATIENTS AND METHODS: Group A (n = 152), was studied at 24-28
      weeks and group B (n = 214) was studied at 32-36 weeks, after an overnight
      fasting a 75 g glucose load was provided and a blood sample was taken after 2 h.
      Glucose levels > 140 mg/dL were diagnostic of GD, women with glucose levels in
      the range of 140-199 mg/dL were prescribed dietary recommendations, but women
      with glucose levels > 200 mg/dL were treated with insulin. Newborns were
      considered macrosomic if weighted > 4,000 g and large for gestational age if
      exceeded the 97th percentile or the Lubchenko scale, both conditions are
      described as macrosomia in the text. Comparisons were done using the Chi-square
      and Fisher exact tests. RESULTS: In group A GD was diagnosed in 27 women
      (17.76%), but only three of them (1.97%) had glucose levels > 200 mg/dL and in
      group B-GD was diagnosed in 62 women (28.97%), but only eight of them (3.73%) had
      glucose levels > 200 mg/dL. The difference in rates between groups A and B was
      significant (p < 0.01). In group A, normal women had 19 (15.2%) macrosomic
      newborns and women with GD had nine (33.33%) macrosomic newborns, this difference
      was significant (p < 0.05); however, in group B women with GD vs. normal, had 10
      (16.12%) and 19 (12.5%) macrosomic newborns, respectively (p = ns). CONCLUSIONS:
      The new criteria for GD diagnosis increases notoriously its prevalence in our
      population to 17.76% at the beginning of the third trimester, comparing with
      1.97% of women with glucose levels > 200 mg/dL applying the WHO criteria for
      diabetes in nonpregnant adults, however, comparing the newborns weight of normal
      women vs. GD women the prevalence of macrosomia was almost the double, reflecting
      the importance of this diagnosis in perinatal health. Women screened at the end
      of pregnancy had a significant increase in GD prevalence, but macrosomia was not
      different of the normal women of this group suggesting that GD at this stage of
      pregnancy may help to detect women with a higher risk to develop diabetes, but
      have no impact on perinatal health.

PMID- 14968472
TI  - Reliability and accuracy of a cardiovascular risk questionnaire and body shape
      figures for body size in Mexican obese subjects.
AB  - There is little information about the validity of questionnaires used by research
      related to obesity. The aim of this study was to demonstrate the reliability and
      accuracy of a cardiovascular risk questionnaire and perception of body size
      pictorials (BSP) measured in Mexican obese subjects. This was a cross-sectional
      study designed as two independent phases. The aims were: a) To calculate a
      concordance index between questionnaires and clinical records. b) To measure the
      reliability of the questionnaire and BSP by test-retest. Phase one: Eighty-four
      subjects were invited to answer the questionnaire (the average age was 46.1 +/-
      14.9 years, BMI 36.4 +/- 7.2). The concordance obtained for heart attack, type 2
      diabetes mellitus and high blood pressure was greater than kappa 0.6. High uric
      acid, hypercholesterolemia and hypertriglyceridemia showed low concordance. Phase
      two: One hundred and two subjects were invited (the average age was 50.8 +/- 14.4
      years, IMC 35.6 +/- 6.8). A high concordance in test-retest (ri = 0.71, p <
      0.001) and for correlation coefficients between BSP and BMI (r = 0.72, p < 0.01)
      was found. CONCLUSION: These data suggest that this questionnaire is reliable and
      data regarding diagnosis of type 2 diabetes mellitus, heart attack and high blood
      pressure are accurate in people who have been treated in hospital. Obese subjects
      are able to classify with accuracy their own BSP and that of other individuals.
      This kind of perception was not altered.

PMID- 14968473
TI  - [Effect of zinc supplements on the nutritional status of patients undergoing
      continuous ambulatory peritoneal dialysis].
AB  - OBJECTIVE: To test the effect of zinc supplementation on the nutritional status
      of patients on continuous ambulatory peritoneal dialysis (CAPD). MATERIAL AND
      METHODS: Double-blinded randomized controlled clinical trial. Twenty-five
      patients with end stage renal disease (ESRD) on CAPD program, from 16 to 60 years
      old were studied. Two weeks before the beginning of the study all the drugs with
      a known effect on zinc absorption were withdrawn. Patients were randomly
      allocated into one of two groups. The control group consisted of 12 patients
      receiving placebo, and the intervention group of 13 patients receiving 100 mg/day
      of elemental zinc for 3 months. The diet was individually adjusted to 35
      kcal/kg/day, and 1.5 g/day of proteins. Subjective global assessment (SGA),
      anthropometric measurements, electric bioimpedanciometry, measurements of
      albumin, prealbumin, and transferrin, and evaluation of energy, proteins,
      carbohydrates, and lipids consumption were done to classify the nutritional
      status at the beginning and at the end of the study. Therapeutic compliance was
      assessed by measuring plasma zinc levels and by capsule counting. RESULTS: There
      were no statistically significant differences between groups regarding age,
      gender, time on CAPD, and ESRD causes. The proportion of patients classified as
      well nourished, or with mild or moderate malnutrition by SGA did not show
      significant differences between the group receiving Zn supplementation and the
      group receiving placebo. Anthropometric measurements and body composition
      assessed by bioelectric impedance were similar in the two groups. In the control
      group, serum levels of albumin (3,621 +/- 838 vs. 3,068 +/- 842 mg/dL),
      prealbumin (49 +/- 14 vs. 44 +/- 12 mg/dL), and transferrin (238 +/- 94 vs. 195
      +/- 79 mg/dL) decreased significantly at the end of the follow-up period respect
      to the baseline values (p < 0.05). In the intervention group albumin (3,320 +/-
      910 vs. 2,696 +/- 964 mg/dL), prealbumin (43 +/- 9 vs. 38 +/- 8 mg/dL), and
      transferrin (236 +/- 99 vs. 193 +/- 66 mg/dL) also decreased significantly (p <
      0.05). In the control group baseline zinc level was low (60 +/- 5 micrograms/dL)
      and remained stable along the follow-up period, while in the intervention group
      it increased from 52 +/- 5 (baseline) to 92 +/- 9 micrograms/dL (end of the
      follow-up, p < 0.05). CONCLUSIONS: Zinc supplementation did not improve the
      nutritional status in patients on CAPD.

PMID- 14968474
TI  - [Changes of physical and functional characteristics in soccer players].
AB  - The purpose of this study was to examine the trends in selected physical
      cardiovascular and metabolic variables in 248 first division professional soccer
      players within a period of 27 years (1973-2000). METHOD: In a cross sectional
      study (panel) 198 Mexican players and 50 mainly from Brazil and Argentina were
      evaluated for physical examination, body composition, blood samples, EKG and
      maximal oxygen uptake on a treadmill. Data were categorized by decade (70's n =
      66, 80's n = 84 and 90's n = 98) and analyzed for significant differences by
      ANOVAS (p < 0.05). RESULTS: Value are presented in mean +/- standard deviation in
      chronological order. Age (years) 24 +/- 2, 26 +/- 2 and 27 +/- 3*. Weight (kg) 74
      +/- 4, 73 +/- 4 and 74 +/- 5. Height (cm) 173 +/- 4, 175 +/- 4 and 176 +/- 5*.
      Body fat (%) 15 +/- 4, 12 +/- 4& and 10 +/- 4#*. Total cholesterol (mg/dL) 246 +/
      26, 220 +/- 24 and 198 +/- 20*. Triglycerides (mg/dL) 172 +/- 24, 190 +/- 26 and
      147 +/- 24*#. Resting heart rate (bpm) 66 +/- 6, 60 +/- 4& and 54 +/- 5*#. VO2
      max (mL.kg-1.min-1) 52 +/- 3, 54 +/- 2 and 57 +/- 2*. (& = p < 0.05 70's vs.
      80's, * = p < 0.05 70's vs. 90's, # = p < 0.05 80's vs. 90's). CONCLUSION: Our
      findings indicated that soccer players performing in the 90's are older and
      taller, lower body fat, lower blood in lipids profile, and higher cardiovascular
      fitness than those performing in the decade 70's and 80's. In particular these
      findings might be related to the improvement at international setting of the
      South American and Mexican soccer level. Despite the favorable changes and the
      personal claim of great skill in these players more physiological gains must be
      aimed and acquired in order to compete in similar circumstances with national
      teams of superior international levels.

PMID- 14968475
TI  - [Comorbidity of obesity and eating behavior disorders].
AB  - In the few years various factors that influence obesity have been studied,
      including genetic, sociocultural, metabolic and endocrine factors. Research
      advances in this area will help enhance our knowledge, prevention and treatment
      of this syndrome. OBJECTIVE: Our first aim is to establish comorbidity between
      obesity and eating disorders (i.e., binge eating disorder, compulsive overeating
      disorder and bulimia). Our second aim is to establish the relation between
      psychiatric diagnoses and sociodemographic, anthropometric, endocrine and
      psychological variables. METHOD: We interviewed 97 outpatients that attended a
      specialized clinic for obesity control in Mexico City, 67 females and 30 males.
      These patients were interviewed by a nutrition specialist, an endocrinologist and
      a psychiatrist, all working in the obesity clinic. For the psychiatric diagnoses,
      DSM-IV criteria were applied to analyze the clinical information on the charts.
      RESULTS: Of all patients in the group 13.4% presented no psychiatric disorder,
      53.6% met criteria for binge eating disorder, 12.4% for type six NOS-ED (Not
      Otherwise Specified Eating Disorder) (compulsive overeating) and 20.6% for
      bulimia. Endocrine disorders were found as follows: 80.4% presented no endocrine
      disorder, 11.3% diabetes mellitus, and 8.2% other diagnoses. Obesity degree: 8.2%
      normal weight, 28.9% overweight, 37.1% type 1 obesity, 18.6% type II obesity and
      7.2% extreme obesity; binge eating disorder was related to all obesity types.
      Bulimic patients had a greater energetic expenditure. Patients with psychiatric
      disorders generally did not present endocrine comorbidity, only 13.4%
      comorbidity. The number of treatments to reduce weight was in direct relationship
      to patients with psychiatric disorders. Patients with a largest calorie intake
      presented binge eating disorder with more eating periods per hay. In sum, by
      measuring anthropometric variables and some nutritional variables, such as the
      way of eating and calorie intake, it was easier to predict eating disorders in
      obese patients. The medical variables themselves were not associated to the
      mental health of obese patients. CONCLUSIONS: We found there is an important
      relation between obesity and psychiatric disorders and we consider it necessary
      to undertake further multidisciplinary, longitudinal and prospective studies in
      other groups of patients or non patients.

PMID- 14968476
TI  - [New molecular features of cholestatic diseases of the liver].
AB  - Hepatic uptake and biliary excretion of bile salts and non-bile salt organic
      anions is mediated by specific transport proteins located at the basolateral and
      canalicular membranes of hepatocytes. Several hepatobiliary transport systems
      have been identified and cloned over the past years. This development has
      facilitated molecular biological and genetic analyses of these transporters in
      experimental cholestasis and human cholestatic liver diseases. Evidence now
      exists that decreased or even absent expression of hepatobiliary transport
      systems may explain impaired transport function resulting in hyperbilirubinemia
      and cholestasis. This review summarizes the molecular defects in hepatocellular
      membrane transporters associated with hereditary and acquired forms of
      cholestatic liver diseases. The increasing information on the molecular
      regulation of hepatobiliary transport systems should bring new insights into the
      pathophysiology and treatment of human cholestatic liver diseases.

PMID- 14968477
TI  - [Up-date on the surgical management of breast cancer].

PMID- 14968478
TI  - [Current concepts on celiac disease physiopathology].
AB  - Celiac sprue (CS) is defined as a chronic small bowel malabsorption disorder
      caused by ingestion of gluten, affecting those genetically predisposed
      individuals. It is characterized by intestinal villi atrophy, increased number of
      intraepithelial lymphocytes and extense inflammatory infiltrate in the intestinal
      lamina propria. The role of gluten as responsible for the intestinal damage seen
      in CS patients is clear, however, the physiopathological mechanisms involved are
      still unknown. Several factors and theories have been proposed: 1) Genetic
      predisposition, based on the association to mendelian factors as well to the
      presence of particular major histocompatibility complex (MHC) haplotypes in CS
      patients; 2) Immunological factors, that consider the derangements that occur in
      the immune response of CS patients, and 3) Gliadin partial deamination by the
      tissular transglutaminase (tTG). In an effort to explain all these complex
      mechanisms, recently, all these theories have been unified, yielding one complex
      physiopathogenic mechanism that we tray to explain in the present review.

PMID- 14968479
TI  - [Antibodies and physiopathogeny of autoimmune hepatitis].
AB  - Autoimmune hepatitis (AIH) is an inflammatory disease of unknown cause
      characterized by periportal hepatitis, increased serum globulins and the presence
      of certain antibodies. The disorder can be classified in three types. Type 1 AIH
      is characterized by the presence of antinuclear antibodies (ANA) and smooth
      muscle autoantibodies (SMA) in up to 70-80% of patients. ANA and SMA can be the
      only antibodies present in 13 and 33% of cases respectively. Type 2 AIH is
      defined by the presence of liver and kidney antimicrosomal antibodies (LKM1).
      Type 2 AIH is the only form of the disease in which the autoantigen has been
      identified: cytochrome mono-oxygenase (P-450 IID6) CYP2D6. In type 3 AIH the
      presence of anti-SLA/LP (soluble liver antigen/liver pancreas) targets a
      cytosolic protein involved in the incorporation of selenocysteine into peptidic
      chains. The pathophysiology of AIH is complex and involves genetic
      predisposition, previous exposure to antigens (autoantigens), presence of
      triggering factors and defects in immunoregulation. In spite of the advances in
      the understanding of AIH, the role of autoantibodies in the pathophysiology of
      this disease has not been fully established and their presence does not clearly
      distinguish any prognostic groups. Further investigations will help in the
      diagnosis of this disorder, the comprehension of its origins and the
      establishment of new forms of treatment.

PMID- 14968480
TI  - Attitudes, values and beliefs of mental health workers.

PMID- 14968481
TI  - Expressed emotion of professionals towards mental health patients.

PMID- 14968482
TI  - Professional attitudes to psychiatric patients: a time for change and an end to
      medical paternalism.

PMID- 14968483
TI  - Is there a continuum of psychotic experiences in the general population?
AB  - AIMS: Schizophrenia is a severe mental illness that affects 1% of the population.
      The diagnosis is made according to current diagnostic systems of DSM-IV (American
      Psychiatric Association, 1994) and ICD-10 (World Health Organisation, 1992), on
      the basis of characteristic 'positive' and 'negative' symptoms. The traditional
      model assumes a categorical view of the schizophrenia syndrome and its core
      symptoms, in which differences between psychotic symptoms and their normal
      counterparts are considered to be qualitative. An alternative, dimensional
      approach assumes that schizophrenia is not a discrete illness entity, but that
      psychotic symptoms differ in quantitative ways from normal experiences and
      behaviours. This paper reviews evidence for the continuity of psychotic symptoms
      with normal experiences, focusing on the symptoms of hallucinations and
      delusions. METHODS: A qualitative review of the relevant literature. RESULTS: The
      literature suggests that although current epidemiological approaches yield
      substantial evidence for a continuum view, it is rarely interpreted as such.
      CONCLUSIONS: The traditional concept of schizophrenia as a homogeneous disease
      entity has become outdated and is in dire need of a more valid and clinically
      useful successor.

PMID- 14968484
TI  - [Socioeconomic inequalities and mental health. II. Methodological aspects and
      literature review].
AB  - OBJECTIVE: This study provides a framework for mental health inequalities
      beginners. It describes the methods used to measure socio economic inequalities
      and the inter-relations with different aspects of mental health: residence,
      mental health services organisation and main diagnostic categories. METHOD:
      Literature electronic-search on Medline, Psyclit, Econlit, Social Science Index
      and SocioSearch using and relating the key-words inequalities, deprivation,
      poverty, socio-economic status, social class, occupational class, mental health
      for the period 1965-2002 (June). The articles selected were integrated with
      manual search (publications of the same authors, cross-references, working
      documents and reports of international and regional organisations). RESULTS:
      Inequality is not an absolute concept and, mainly, it has been changing during
      the last years. For example, the integration and re-definition of variables that
      capture, in simple indices, a complex reality; the accent on social more than on
      economic aspects; the geo-validity and time-reference of the inequality's
      indices. Moreover, the inequalities could be the result of individual
      preferences, in this case, the social selection and social causation issues will
      raise the suitability for a public intervention. CONCLUSIONS: Up to now, research
      has been mainly concentrated in describing and measuring health inequalities. For
      designing effective interventions, policy makers need to ground decisions on
      health-socioeconomic inequalities explanatory models.

PMID- 14968485
TI  - [Systemic review of clinical interventions for reducing treatment non-adherence
      in psychosis].
AB  - AIMS: Studies investigating the efficacy of clinical interventions for reducing
      treatment non-adherence have generated contrasting findings, and treatment non
      adherence remains very common in clinical practice. This systematic review was
      carried out to investigate the efficacy of clinical interventions that community
      psychiatric services can implement to reduce non-adherence in patients with
      psychosis. METHOD: Systematic review of randomised clinical trials, controlled
      clinical trials and observational studies assessing the efficacy of adherence
      enhancing interventions. RESULTS: Forty-seven studies met the inclusion criteria
      and were included in this systematic review. Data suitable for re-analysis were
      reported in 24 studies; from the remaining 23 studies, with no data suitable for
      re-analysis, outcome data were extracted according to what study authors
      reported. In the group of studies included in the meta-analysis educational and
      psychotherapeutic interventions were more effective than usual care in reducing
      patient non-adherence. The remaining 23 studies reported contrasting findings
      regarding the efficacy of educational strategies. Case management models improved
      the adherence in half of studies, while other interventions were effective in the
      majority of studies reported. CONCLUSIONS: Community psychiatric services can
      arrange effective clinical interventions, backed by scientific evidence, for
      reducing patient non-adherence.

PMID- 14968486
TI  - [Psychotropic drug use in a sample of general population in the Sardinia region].
AB  - AIMS: To present the results of an epidemiologic research about psychotropic drug
      use in Sardinia. METHODS: Cross-sectional study on a sample of 1040 subjects
      randomly selected from registers. SETTING: Community survey on three areas of
      Sardinia region. EVALUATION: Interviews carried out by physicians by means of
      Italian version of the Composite International Diagnostic Interview Simplified.
      Drug consumption was evaluated concerning last week before the interview. MAIN
      OUTCOME MEASURES: Point prevalence. RESULTS: The rate of adults of the general
      population that consumed benzodiazepines was 10.1%, antidepressants 4.2%, 14.7%
      of the sample was using psychotropic drugs. 60% of subjects with diagnosis of ICD
      10 Depressive Episod did not have the right pharmacologic treatment. A relevant
      proportion of subjects without lifetime psychiatric diagnosis (anxiety and/or
      depression) used antidepressants (0.8%). The pharmacologic therapies were managed
      by psychiatrics in 44.2% of cases, antidepressants were managed by general
      practitioners in 31.8% of subjects. CONCLUSIONS: The research underlines an
      increase of meet needs in subjects affected by depressive episodes against a
      previous Sardinian survey carried out over ten years ago. This change is parallel
      to a more frequent management of therapies by general practitioners. Their role
      seems to become more relevant in treating depressive illness.

PMID- 14968487
TI  - [Eating psychopathology and personality in eating disorders].
AB  - OBJECTIVE: The question of how many psychopathologic factors are involved in
      Anorexia Nervosa (AN) and Bulimia Nervosa (BN) has no definite answer. The
      combination of psychopathology and personality research may shed a light upon the
      determinants of eating pathology. METHODS: The study consists in the
      administration of the Temperament and Character Inventory (TCI) and the Eating
      Disorder Inventory 2 (EDI-2) to 95 outpatient anorectic women (50 restrictive and
      45 binge-purging) and to 92 bulimic outpatient women (78 with and 14 without
      purging behaviours). The respective scores of each DCA subgroup are compared.
      RESULTS: Restricter anorectics are characterised by lower novelty seeking on
      respect to all the other groups and by a higher self-directedness on respect to
      bingeing-purging anorectics and purging bulimics. Also psychopathologic
      differences between restricter anorectics and the other groups are extensive.
      Bingeing-purging anorexia shares many traits with bulimia. CONCLUSIONS: In their
      complex, data suggest and in-deep study aimed to a possible re-classification of
      EDs which would take impulsiveness in greater consideration. The differences in
      temperament and character traits may partially be responsible of the repression
      or discontrol of impulsive eating behaviours in different ED subtypes.

PMID- 14968488
TI  - Does training in hospice care affect referrals?

PMID- 14968489
TI  - Ars moriendi: the art of dying.

PMID- 14968490
TI  - The test-and-treat strategy for Helicobacter pylori in uninvestigated dyspepsia.

PMID- 14968491
TI  - Dealing with the incompetent supervising physician: an ethical dilemma.

PMID- 14968492
TI  - Polycystic ovary syndrome--a complex disorder among women.

PMID- 14968493
TI  - Performing a fluorescein examination of the eye.

PMID- 14968494
TI  - Disease: why I'm against it.

PMID- 14968495
TI  - On the brink, and over.
AB  - All in all, this has been a most successful and rewarding period of time for the
      Academy. Most rewarding of all, perhaps, is the increased recognition being given
      to the AAPA as a leader among membership organizations in the United States. This
      recognition underscores our continued commitment and growing capability to help
      our members and advance the PA profession in the interest of all patients.

PMID- 14968496
TI  - Beignets, inspiration, mudbugs, and CME. Voices from the 31st annual conference.

PMID- 14968497
TI  - Using insulin pump therapy to achieve normoglycemia.

PMID- 14968498
TI  - A guide to swift recognition of dangerous arthropod bites and stings.

PMID- 14968499
TI  - Diagnosing a patellar fracture.

PMID- 14968501
TI  - Melding high-tech medicine with high-touch patient care.

PMID- 14968500
TI  - Current treatments for allergic rhinitis and asthma.

PMID- 14968502
TI  - Assessing and managing ophthalmic emergencies.

PMID- 14968503
TI  - B-natriuretic peptide in the management of heart failure.

PMID- 14968504
TI  - Recognizing problem gambling in primary care.

PMID- 14968505
TI  - Weighing the risks and benefits of hormone therapy.

PMID- 14968506
TI  - Contemporary concepts of physician supervision.

PMID- 14968507
TI  - The nursing shortage is everyone's problem.

PMID- 14968508
TI  - When to suspect--and how to manage--pelvic inflammatory disease.

PMID- 14968509
TI  - Understanding the array of presentations: reflex sympathetic dystrophy.

PMID- 14968510
TI  - Assessing facial fractures in the emergency department.

PMID- 14968511
TI  - Current approaches to the management of epistaxis.

PMID- 14968512
TI  - Improving trauma outcomes: control is still key.

PMID- 14968513
TI  - Revising anticoagulation guidelines for the prevention of recurrent VTE.

PMID- 14968514
TI  - Cervical spine clearance in adult trauma patients.

PMID- 14968515
TI  - Managing dog, cat, and human bite wounds.
AB  - All bite wounds require the same general approach regarding history and physical
      exam, selective ancillary testing, wound cleaning, and immobilization. Primary
      closure should be considered only for bites in which the concerns about cosmetic
      outcome outweigh the risk of infection. Antibiotic prophylaxis should be
      initiated for patients with high-risk bite wounds and for those who are at risk
      for serious wound infection complications. The chosen antibiotic should cover
      beta-lactamase-producing aerobic and anaerobic organisms, including Pasteurella
      species in animal bites and E corrodens in human bites.

PMID- 14968516
TI  - Pain management in the emergency department.

PMID- 14968517
TI  - Closed head injury in elderly and nonelderly patients.
AB  - AIM: To investigate differences in clinical presentation between elderly and
      nonelderly patients with traumatic closed head injury (CHI). METHODS: A
      retrospective chart review was used to compare the initial presentation of
      elderly versus nonelderly adult patients evaluated at two trauma centers with a
      final diagnosis of CHI confirmed by computed tomography (CT). RESULTS: Of 171
      patients who met inclusion criteria, 114 (67%) were placed in the nonelderly
      group and 57 (33%) in the elderly group. Loss of consciousness was reported in 28
      patients (49%) in the elderly group compared to 76 patients (67%) in the
      nonelderly group (diff = 0.18, 95% confidence interval [CI] 0.02-0.34).
      CONCLUSION: Elderly patients with traumatic CHI appear to experience loss of
      consciousness less frequently than nonelderly patients. Loss of consciousness
      should not be the sole determinant of the need for CT in elderly patients with
      head trauma.

PMID- 14968518
TI  - Evaluating thoracoabdominal trauma with ED ultrasonography.

PMID- 14968519
TI  - Increasing hip pain after a fall.

PMID- 14968520
TI  - Removing a fishhook.

PMID- 14968521
TI  - POEMs for PAs.

PMID- 14968522
TI  - National Kidney Foundation develops practice guidelines for chronic kidney
      disease.

PMID- 14968523
TI  - Recognition and management of gout and hyperuricemia.

PMID- 14968524
TI  - Pharmacotherapeutic approaches to treatment-resistant depression.

PMID- 14968525
TI  - Medical abortion with mifepristone: an update.

PMID- 14968526
TI  - Clubbing and hip pain in a long-term smoker.

PMID- 14968527
TI  - Expanding our concept of the medical literature: the value of the humanities in
      medicine.

PMID- 14968528
TI  - [Sexual differentiation and its abnormalities].

PMID- 14968529
TI  - [Sex differentiation and sex chromosomes].
AB  - The mechanisms for sex differentiation and the genes on the sex chromosomes are
      varied among different species. For human, SRY is the only testis-determining
      factor on the Y chromosome and triggers the cascade for male sex-determination.
      However, even if normal SRY exists, the haploinsufficienty of SOX9 or KTS+
      splicing form of WT-1 can cause male-to-female sex reversal. Furthermore, the
      duplication of the partial region on the X chromosome including DAX-1 gene can
      also cause male-to-female sex reversal. The sex-determining system seems to be
      sensitive for the gene dosage or the gene expression level.

PMID- 14968530
TI  - [Sex differentiation of the gonads and regulation of gene expression].
AB  - Loss-of-function and gain-of-function studies have revealed that several
      transcription factors and growth factors are implicated in gonad differentiation.
      In fact, the mice in which certain genes encoding transcription factors or growth
      factors are disrupted or overexpressed showed a variable defects in gonad
      differentiation and gonad sex determination. These phenotypes together with the
      symptoms of the corresponding human diseases indicated the functional
      significance of the genes. Although these studies largely contributed to identify
      the components essential for the gonad differentiation and gonad sex
      determination, functional relation among the components remained to be
      elucidated. Elucidation of the genetic cascade will help us to understand the
      molecular mechanisms underlying gonad differentiation and gonad sex
      differentiation.

PMID- 14968531
TI  - [Differentiation and development of internal sexual organs, and mullerian
      inhibiting substance].
AB  - Internal sexual organs are differentiated and developed by androgens and
      regressed by mullerian inhibiting substance(anti-mullerian hormone). The role of
      5 alpha-dihydrotestosterone, reduced form of testosterone by 5 alpha-reductase,
      in terms of development of Wolffian duct is discussed with soluble mesenchymal
      factor responsible for the epithelial branching morphogenesis of mouse seminal
      vesicle on the basis of experimental results using organ culture assay of mouse
      new-born seminal vesicle. An update of mullerian inhibiting substance, a fetal
      regressor of female internal organs such as uterus, fallopian tubes and upper
      third vagina, is also discussed.

PMID- 14968532
TI  - [Differentiation of external genitalia and 5 alpha-reductase].
AB  - Sexual differentiation of the external genitalia depends on many factors such as
      genetic sex, gonadal sex or androgen action. Among them, 5 alpha-reductase plays
      an important role in androgen action: dihydrotestosterone(DHT) is produce from
      testosterone by 5 alpha-reductase and DHT binds the androgen receptor to induce
      the differentiation of the external genitalia. In this paper we reviewed on the
      mechanism of the differentiation of the external genitalia, especially on the
      relation with androgen action and 5 alpha-reductase.

PMID- 14968533
TI  - [Sex differentiation of central nervous system--brain of man and woman].
AB  - Sex differentiation of human brain is mostly dependent on the prenatal exposure
      to androgen(testosterone). Congenital aromatase deficiency does not disturb male
      brain development in men. This is quite different from experimental evidence from
      rodents whose brains need intraneuronal aromatization from androgen to estrogen
      to induce sex differentiation. There is evidence for male-female differences in
      brain structures. Some of them(INHA-3) appear to be related with sexual
      orientation. The other(BNST) might participate in forming gender-identity. In
      addition, sexually dimorphic features are recognized in some cognitive
      activities. The possible involvement of genetic factors in human brain sex
      differentiation is also discussed.

PMID- 14968534
TI  - [Grouping of abnormal sexual development--guide to diagnosis].
AB  - Sexual differentiation and development is a process from the moment of
      fertilization of a ovum by a spermatozoon to achievement of reproductive ability
      as a male or female. The process includes three steps; establishment of sex
      chromosome composition, gonadal differentiation and development, and acquirement
      of phenotypic expression by gonadal hormones. Therefore, abnormal sexual
      development is divided into three categories according to the above three steps.
      In humans, however, gender is assigned at birth. Then, individuals grow under
      social environment provided according to the gender assigned and acquire gender
      role during childhood and gender identity during puberty. As observed in those
      with trans-sexualism, it appears likely that gender identity plays a major role
      on sexual behavior of humans.

PMID- 14968535
TI  - [True hermaphroditism].
AB  - True hermaphroditism in humans is defined as the simultaneous presence of both
      testicular and ovarian tissue in a single individual. I reviewed clinical
      findings, karyotype, findings of recent molecular analysis, diagnostic tools and
      treatment of true hermaphroditism. Recent molecular analysis in true
      hermaphroditism revealed that duplication of 22q was recognized in a 46,XX SRY
      negative case. A 46,XX true hermaphrodite in which SRY was negative in blood
      leukocytes and epithelial oral cells but present and partially deleted in DNA
      obtained from the testicular portion of the ovotestes was reported. And also, the
      study using PCR and FISH analyses revealed the presence of hidden mosaicism for
      SRY or other Y sequences in some patients with XX true hermaphroditism and
      mosaicism for SRY limited to the gonads is an alternative mechanism for
      testicular development in 46,XX true hermaphrodites.

PMID- 14968536
TI  - [XX 'pure' gonadal dysgenesis and XYY syndrome].
AB  - XX 'pure' gonadal dysgenesis is a disease related to Turner's syndrome. Patients
      of this disease are characterized by normal female external genitalia, bilateral
      streak gonads, amenorrhea and sexual infantilism. Recently, it has been reported
      that point mutations of the FSH receptor gene may be one of cause of this
      disease. The relationship between criminal behavior and XYY syndrome is still
      controversial. Increased incidence of disomic sperm in 47,XYY males has been
      reported by fluorescent in situ hybridization(FISH). Genetic counseling should be
      done when they undergo intracytoplasmic sperm injection.

PMID- 14968537
TI  - [XY type gonadal dysgenesis, trisomy X and variants].
AB  - Sex determination and differentiation depend on differentiation of the
      indifferent gonad to the testis or ovary, which leads to masculine or feminine
      differentiation of internal and external genitalia. Recently, genes involved in
      this cascade have been identified with the advance of molecular genetical
      analysis. XY gonadal dysgenesis, this is a condition that has XY chromosome but
      is characterized by the indifferent testis. There are complete and incomplete
      types. Complete type has bilateral gonads of cordee, does not show physical
      characteristics of Turner's syndrome, has the uterus and ovaries, and has the
      vagina in female type, though the external genitalia are immature. Incomplete
      type is characterized by bilateral testicular hypoplasia(male
      pseudohermaphroditism) or unilateral testicular hypoplasia and bilateral
      restiform gonads(mixed gonadal dyspenesis), and the sexuality of the external
      genitalia is unclear. XX gonadal dysgenesis, complete type is characterized by
      bilateral restiform gonads, female type internal and external genitalia and
      sexual immaturity, though it does not show any characteristics of Turner's
      syndrome. It presents hypergonadotropic hypogonadism endocrinologically. It shows
      a familial incidence with autosomal recessive inheritance, and sensorineural
      deafness is accompanied in some cases. Incomplete type has rudimentary ovaries
      and show a varying degree of secondary sexual characteristics. Mixed dysgenesis,
      many cases have XO/XY mosaic and this dysgenesis is characterized by unilateral
      hypoplastic testis and contralateral restiform gonad. It may occur in cases of
      incomplete type XY gonadal dysgenesis. Trisomy X, cases of trisomy X have three X
      chromosomes as this term indicates. There are some cases of polisomy with four or
      more X chromosomes. The frequency of trisomy X has been reported to be one in
      1,000 births of female, which means that it is a relatively common chromosomal
      aberration. It has been reported that about 20% of cases of trisomy X have sexual
      dysfunction, predominantly with primary amenorrha.

PMID- 14968538
TI  - [Mixed gonadal dysgenesis].
AB  - Testicular dysgenesis derives from abnormal gonadal differentiation caused by sex
      chromosome abnormality. Individuals with sex chromosomal mosaicism manifest
      diverse phenotypes from phenotypic females and individuals with mixed gonadal
      dysgenesis (MGD) to males. Gonadal asymmetry in MGD is cytogenetically due to
      local prevalence of cell lines carrying different karyotypes; XO in the streak
      gonad and XY in the dysgenetic testis while sex chromosome abnormalities in blood
      do not always reflect the genital abnormalities. Gender assignment should be
      based on the potential for normal function of the external genitalia under the
      parents agreement. Laparoscopic and microscopic surgery facilitates the diagnosis
      and treatment in infants with MGD and its variants. Close follow-up is mandatory
      for detecting the highly prevalent gonadal tumor in male subjects.

PMID- 14968539
TI  - [Gonadal dysgenesis in Turner syndrome].
AB  - This review article summarizes the current knowledge on the development of
      gonadal dysgenesis in Turner syndrome. The degree of gonadal dysfunction is well
      correlated with the size of unpaired region of the sex chromosomes and is
      independent of the dosage of gene(s) on the sex chromosomes. Thus, it is deduced
      that sex chromosome aberrations result in meiotic pairing failure of homologous
      chromosomes, leading to accelerated oocyte loss and resultant gonadal dysgenesis.
      Although the underlying factor responsible for the oocyte loss remains to be
      determined, it is likely that activation of apoptotic mechanism to prevent the
      generation of abnormal gametes plays an essential role in the rapid oocyte
      degeneration.

PMID- 14968540
TI  - [Klinefelter syndrome].
AB  - Klinefelter's syndrome is defined by males with at least one Y chromosome and at
      least two X chromosomes. It represents the most common major abnormality of
      sexual differentiation. The original description was characterized by
      eunuchoidism, gynecomastia, azoospermia, and small, firm testes. Patients tend to
      be taller than average, mainly because of the disproportionate length of their
      legs. Serum testosterone is low to normal and gonadotropins are elevated.
      Histologically, seminiferous tubules degenerate and are replaced with hyaline.
      Some complications are occasionally found such as neoplasm, osteoporosis,
      autoimmune diseases, and diabetes mellitus. Treatment options include
      testosterone replacement for correction of the androgen deficiency. Recently,
      intracytoplasmic sperm injection(ICSI) of testicular spermatozoa resulted in
      several deliveries.

PMID- 14968541
TI  - [Impaired spermatogenesis and genes].
AB  - The crucial genes for spermatogenesis have not yet been identified, but the AZF
      regions in the Y chromosome are now thought to show a major correlation with
      spermatogenesis. Recently, a complex of palindromes exists in the Yq, and is
      conserved in a highly repetitive sequence. Therefore, the PCR based sequence
      tagged site (STS) could not be accurately decided their unique position. This
      review demonstrated that there was not a high frequency of deletion of AZF
      specific genes than expected using usual STS-PCR. However, the frequency of
      expression in AZF genes is relatively low. This discrepancy is probably due to
      repetitive sequence of complex palindromes in the Yq.

PMID- 14968542
TI  - [Disorder of androgen biosynthesis].
AB  - Disorders of androgen biosynthesis are a relatively rare cause of sexual
      ambiguity in 46XY genetic males. The biosynthesis of androgen requires the
      steroidogenic acute regulatory protein (StAR) and the steroidogenic enzymes
      P450scc, 3 beta HSDII, P450c17, 17 beta HSDIII, and 5 alpha-reductase.
      Deficiencies have been reported in these enzymes, leading to male
      pseudohermaphroditism. Here we describe three enzymes 3 beta HSDII, P450c17, and
      17 beta HSDIII, their roles and mechanisms of action special reference to
      diagnosis and treatment for the patients with deficiencies of these enzymes.

PMID- 14968543
TI  - [Androgen insensitivity syndrome and co-activator disease].
AB  - Androgen insensitivity syndrome(AIS) is a clinical continuum of virilization
      disorders in XY males. Almost AIS is due to mutations in androgen receptor(AR)
      gene. Over 300 mutations in the AR gene have been reported. In addition, we have
      reported the case of complete AIS who has no mutations in AR gene, caused by co
      activator abnormality. The recent advances in live-cell imaging techniques have
      developed a novel concept in AIS.

PMID- 14968544
TI  - [Congenital lipoid adrenal hyperplasia].
AB  - Congenital lipoid adrenal hyperplasia(CLAH) is known as the severest form of
      congenital adrenal hyperplasia, which is characterized by the lack of
      biosynthesis of all steroid hormones and its metabolites due to the failure in
      converting cholesterol to pregnenolone, the first and rate-limiting step of
      steroid synthesis. The genetic etiology has been identified; trafficking defect
      of cholesterol to mitochondria due to defect of StAR gene, and conversion defect
      of cholesterol to pregnenolone at mitochondrial membrane due to the defect of
      CYP11A, cholesterol side chain cleavage enzyme. The advancement of genetical
      analysis has revealed that the clinical feature is not only defined as severe
      salt-loosing and complete failure of musculinization, but also as relatively mild
      or late-onset form. Spontaneous puberty may exhibit to 46,XX patients while 46,XY
      subjects will never show pubertal signs. It suggested that 1) it may take more
      time to deposit lipid particles to cause irreversible damage to ovary than to
      testis, 2) there exists the other ways in cholesterol trafficking which rescue
      the StAR deficiency.

PMID- 14968545
TI  - [Leydig cell hypoplasia(agenesis)].
AB  - Leydig cell hypoplasia(LCH) or agenesis, which has an autosomal recessive
      inheritance pattern, is a well defined form of male pseudohermaphroditism
      resulting from inadequate fetal testicular Leydig cell differentiation. These
      patients exhibit a wide clinical spectrum that ranges from phenotypic females to
      males with micropenis, and have low levels of serum testosterone and elevated
      levels of LH. Recently, it has become clear that defective male sex
      differentiation in patients with LCH is caused by deficient LH receptor signal
      transduction. The fetal Leydig cells of LCH patients fail to respond to adequate
      levels of placental hCG, resulting in inappropriate fetal androgen production. At
      puberty, adult-type Leydig cells do not mature and do not produce sufficient
      androgen for normal secondary sex differentiation.

PMID- 14968546
TI  - [Congenital adrenal hyperplasia due to 21-hydroxylase deficiency].
AB  - 21-hydroxylase deficiency occurring in one of 15,000 live births represents the
      most frequent disorder in female pseudohermaphroditism. Molecular genetic
      analysis is useful for ascertaining disease condition. Newborn mass-screening has
      been conducted in Japan. Prenatal diagnosis and treatment is feasible.

PMID- 14968547
TI  - [Aromatase deficiency].
AB  - Aromatase, a key enzyme in estrogen synthesis, is tissue-specifically regulated
      in various tissues and plays an important role through endocrine and intracrine
      estrogen production in various physiological functions. Therefore, aromatase
      deficiency caused crucial impairments of physiological functions in the gonadal
      tissues as well as extra-gonadal tissues. Because aromatase is protective for
      androgenic exposure by catabolizing, virilization of a pregnant mother and
      pseudohermaphroditism of a baby girl consequently result from the deficiency.
      Similarly, because aromatase is productive for a multifunctional physiological
      factor, estrogens, impaired metabolisms of bone, carbohydrate, and fat etc.
      result from the deficiency. We discuss the etiology, clinical symptoms, and
      therapeusis by classifying it into two types of complete and incomplete aromatase
      deficiencies.

PMID- 14968548
TI  - [Congenital anomalies of the genitourinary tract].
AB  - Genitourinary tract anomalies found at birth arise from a variety of sex
      differentiation disorders occurred during fetal development. It is important to
      know and identify common congenital anomalies of genitalia for disclosing
      underlying genetic and/or endocrine disorders of newborn at very early stage of
      life as well as for determining proper sex of neonate. This article presents
      several genital anomalies from an obstetric point of view and simply describes
      their handlings.

PMID- 14968549
TI  - [Disorders of sex differentiation caused by exogenous hormones].
AB  - Transplacental and lactogenic exposure of fetus and neonate to exogenous hormones
      and endocrine disrupters can cause a range of abnormalities of the reproductive
      system including sex differentiation and sex maturation. Sex differentiation is
      critically dependent on the normal action of androgens and can be disturbed by
      unbalanced androgen/estrogen ratios. Androgenic substances masculinize female
      fetus. Progestogens act both as androgen antagonists, demasculinizing males, and
      as androgen agonists, masculinizing females. Transplacental exposure of male
      fetus to synthetic estrogen diethylstilbestrol is recognized to have led to
      increases in the incidence of cryptorchidism, hypospadia and decreased sperm
      counts. A growing number of endocrine disrupters have been found to possess
      either weak estrogenic, anti-androgenic or other hormonal activities. Increased
      exposure to environmental endocrine disrupters can cause male
      pseudohermaphroditism.

PMID- 14968550
TI  - [Diagnosis and treatment of gender identity disorder].
AB  - According to DSM-IV criteria, gender identity disorder(GID) is characterized as
      follows: 1) Strong, persistent cross-gender identification. 2) Persistent
      discomfort with one's assigned sex or the Sense of inappropriateness in that
      gender role. 3) Not due to an intersex condition. In this chapter, symptoms,
      diagnosis and treatment of GID are briefly described. Possible pathogenesis of
      GID is also discussed.

PMID- 14968551
TI  - [Decision-making process about sex assignment in the neonate with ambiguous
      genitalia].
AB  - Although diagnoses and etiologies of underlying disorders of sexual
      differentiation can be carefully delineated through biochemical, imagine, and
      chromosomal analyses, the decision-making process about sex assignment in the
      newborn with ambiguous genitalia is in a state of controversy. The conventional
      way for the approach to these neonates consists of 4 principles; 1) Urgency of
      diagnosis and sex assignment, so that early surgical reconstruction could obviate
      the fear of the parents with each diaper change. 2) Adequacy of the phallus as a
      male. 3) Fertility, especially 46XX female are sex assigned female because of
      potential fertility. 4) Cosmetic appearance of the reconstructed genitalia based
      on the recognition that external female genitalia are generally easier to
      construct than male. Contrary to these conventional methods, some researchers
      insist on flexibility in the clinical approach to provide the best possible
      outcome. It is getting apparent that the quantity, timing, and duration of
      androgen exposure will play a role in determining the degree of masculinization
      of the brain, which may potentially decide gender identity before 18 months of
      age or even in utero, and may influence the psychosexual development of the
      child. Flexibility in decision-making will allow for options not to remove any
      tissues including gonads and internal sex organs, or to reconstruct the genitalia
      until he or she is sure of the gender. This new approach must be proved in the
      future.

PMID- 14968552
TI  - [The abnormalities of pubertal development: a review of treatment for them].
AB  - Precocious puberty has been defined as the development of secondary sex
      characteristics before 8 years of age in girls. In the past, therapy with
      progestational agents, such as medroxyprogesterone acetate or cyproterone acetate
      had been used. The gonadotropine releasing hormone agonist has been used widely.
      The ethiologies of delayed sexual development are numerous. A series of 191
      patients with delayed pubertal development is reported in this study. Gonadal
      dysgenesis is 39/119(32.8%), physiologic delay is 27/119(22.7%), Rokitansky
      syndrome is 17/119(14.3%), hyperprolactinemia is 11/119(9.2%). The girls with
      physiological delay, hyperprolactinemia or poly cystic ovary syndrome, have
      subsequent normal reproductive potential. In the treatment of abnormal pubertal
      development, the individual treatment is important.

PMID- 14968553
TI  - [Immunophilin FKBP38, an inherent inhibitor of calcineurin, targets Bcl-2 to
      mitochondria and inhibits apoptosis].
AB  - Various apoptotic stimuli induce mitochondrial dysfunction. Bcl-2 and Bcl-xL
      antagonize apoptosis by blocking the release of caspase activators such as
      cytochrome c from mitochondria. We demonstrated that FKBP38, a member of the
      immunophilin family, interacts and targets these anti-apoptotic proteins Bcl-2
      and Bcl-xL, thereby assisting them in their pro-survival role. FKBP38 is
      specifically localized on mitochondria, at which FKBP38 is colocalized with Bcl-2
      and Bcl-xL. Expression of exogenous FKBP38 promotes mitochondrial targeting of
      Bcl-2 and Bcl-xL, while dominant-negative FKBP38 or siRNA of FKBP38 disturbs
      their localization. On the other hand, unlike FKBP12, FKBP38 inhibits
      serine/threonine phosphatase calcineurin in an FK506-independent manner.
      Overexpression of FKBP38 inhibits apoptosis, while expression of dominant
      negative FKBP38 or depletion of endogenous FKBP38 increases the sensitivity for
      apoptosis. Thus, FKBP38 has unique features among members of the immunophilin
      family.

PMID- 14968554
TI  - Urinary excretion of beta-aminoisobutyric acid in hematological diseases.
AB  - The level of beta-aminoisobutyric acid (beta-AIB), a thymine catabolite, has been
      measured in urine samples of 160 healthy individuals, 28 patients with renal, 27
      patients with cardiovascular and 27 patients with hematological diseases and of
      36 tumor patients. No significant difference in the prevalence of high excretors
      of beta-AIB between patients with cancer, renal and cardiovascular diseases and
      the healthy group was found, whereas all but two patients with hematological
      diseases were high excretors. Urinary beta-AIB shows a reverse correlation with
      the hemoglobin level and erythrocyte count in the cases of anemia, and appears to
      be directly correlated with the leukocyte count and blast cell content in the
      cases of leukemia, with its amount decreasing two to five-fold with the return of
      the hematological markers to normal levels after medicinal treatment. Therefore
      the beta-AIB concentration in urine may be used in combination with hematological
      indicators in assessing the disease status and in monitoring of the treatment
      response.

PMID- 14968555
TI  - [Genetic risk factors for ischemic cerebrovascular disease--analysis on fifteen
      candidate prothrombotic gene polymorphisms in the Japanese population].
AB  - Accumulating evidence suggests that several polymorphisms in factors regulating
      blood coagulation, platelet function, and lipid metabolism are relevant for
      susceptibility to ischemic cerebrovascular diseases (CVD). The present study
      analyzed 15 genetic polymorphisms possibly associated with atherosclerosis and
      thrombosis in a case-control study involving a total of 200 genetically unrelated
      Japanese patients with ischemic CVD (mean age 58.3 +/- 7.6 y) and 281 age- and
      gender-matched control subjects (59.0 +/- 4.1 y). Control subjects were randomly
      selected from unrelated donors with no history of documented CVD or any type of
      cardiovascular disease with normal resting electrocardiograms. Among the factors
      genotyped, two factors, platelet glycoprotein (GP) Ib alpha (Thr145Met) and NADPH
      oxidase p22phox (His72Tyr), were significantly associated with CVD after
      adjustment for acquired risk factors including hypertension, diabetes mellitus,
      hyperlipidemia, and smoking. For those with age < 60 y, 10.6% of the CVD patients
      and 2.9% of the control subjects had both of the two risk genotypes (GPIb alpha
      145Met and p22phox 72Tyr, p < 0.05). The mean onset-age of CVD was 58.6 +/- 7.7 y
      for those having no or only one risk genotype, while 53.3 +/- 5.5 y for those
      having both of the risk genotypes (p < 0.05). Thus, GPIb alpha 145Met and p22phox
      72 Tyr are the genetic factors associated with the risk of ischemic CVD in the
      Japanese. Carrying both of the two mutations might be associated with developing
      CVD at a younger age.

PMID- 14968556
TI  - [Two cases of parasitic granuloma found incidentally in surgical specimens].
AB  - Occasionally, parasitosis demonstrates no clinical symptoms, and is found
      incidentally. We report 2 cases of parasitic granuloma found incidentally in
      surgical specimens in rare sites for parasitosis. Case 1 was a 40-year-old
      female. She was diagnosed with inguinal hernia, and operation was performed. A
      white nodule, measured 1.5 x 1 x 1 cm in size, was found in the hernia sac. The
      nodule was elastic hard and solid. Histologically, eosinophilic granuloma was
      demonstrated, and the parasite was characterized by renette cell and Y-shaped
      lateral cord, and suggesting extra-gastrointestinal anisakiasis. Case 2 was a 71
      year-old female. She was diagnosed with colonic adenocarcinoma, and colectomy was
      performed. A white nodule, measured 1 x 1 x 0.8 cm in size was found in the
      omentum, at first identified as peritoneal dissemination of colonic carcinoma.
      However, histological findings of the nodule showed eosinophilic granuloma, and
      parasite was observed in the granuloma. The parasite was characterized by thick
      cuticle and muscular cells, and suggestive of dilofilariasis. In each case, no
      clinical symptoms of parasitosis were recognized, and each lesion presented in a
      rare site as anisakiasis or dirofilariasis. When any lesions as in the present
      cases is found in a surgical specimen, it is important to make differential
      diagnosis with consideration for parasitic granuloma.

PMID- 14968557
TI  - Self-assembly of HDL network on mica.
AB  - The structure of high-density lipoprotein (HDL) is a subject that continues to
      attract interest. The goal of this study is to observe the self-assembly
      construction of HDL on mica using atomic force microscopy (AFM). On mica, HDL was
      observed to form a honeycomb-like network formation. The narrowest part of the
      HDL wire was approximately 5.6 nm. HDL can be used in the microcircuitry of
      electronic devices and is of great interest in the field of nanotechnology.

PMID- 14968558
TI  - ["Process of the research and development received Nobel Prize in Chemistry
      2002"].
AB  - Mr. K. Tanaka engaged in Shimadzu Corporation received the Nobel Prize in
      Chemistry 2002 for the development of soft laser desorption ionization method for
      mass spectrometric analyses of biological macromolecules. In this paper, the
      process of the research and development of desorption ionization method and the
      produced laser desorption ionization time of flight mass spectrometer (LDI-TOFMS)
      are described.

PMID- 14968559
TI  - [Differential diagnosis of hepatitis: development of new laboratory tests for
      autoimmune hepatitis and progress in pathophysiology].
AB  - Liver dysfunction has been found in 8.1% of postpartum women in the general
      population. This dysfunction was speculated to be developed by postpartum
      aggravation of subclinical autoimmune hepatitis. Therefore, we developed two
      methods for detection of autoantibodies to liver-specific antigens: an ELISA for
      anti-liver-specific arginase antibodies, and a highly sensitive radioligand assay
      for anti-CYP2D6 antibodies. Basic examinations of dilution curve, inhibition
      study and reproducibility were satisfactory for clinical application in both
      assays. Anti-arginase antibodies and anti-CYP2D6 antibodies were found in 28.6%
      and 42.6% of patients with autoimmune hepatitis, respectively. There was no
      correlation between the two autoantibodies and thus, combined use of these
      antibodies detects 55.3% of autoimmune hepatitis. Autoimmune hepatitis exists
      frequently when we include mild cases.

PMID- 14968560
TI  - [Establishment of assay system for fibroblast growth factor (FGF)-23 and
      pathophysiological roles of FGF-23 in the development of hypophosphatemic
      diseases].
AB  - Rickets/osteomalacia is characterized by impaired mineralization of bone matrix.
      X-linked hypophosphatemic rickets/osteomalacia(XLH), autosomal dominant
      hypophosphatemic rickets/osteomalacia(ADHR) and tumor-induced
      rickets/osteomalacia(TIO) share common clinical features including impaired
      proximal tubular phosphate reabsorption. Fibroblast growth factor(FGF)-23 was
      positionally cloned as a responsible gene for ADHR. We have also cloned FGF-23 as
      a causative factor for TIO. FGF-23 is a polypeptide with 251 amino acids. FGF-23
      is proteolytically cleaved between Arg179 and Ser180 and only full-length FGF-23
      showed biological activity to induce hypophosphatemia. Using two monoclonal
      antibodies that recognize N-terminal and C-terminal portion of the processing
      site of FGF-23, sandwich enzyme-linked immunosorbent assay for FGF-23 was
      established. This assay detects only full-length FGF-23. Circulatory level of FGF
      23 in healthy controls distributed between 10 to 50 pg/ml suggesting that FGF-23
      is a physiological humoral factor. FGF-23 levels in patients with TIO were
      elevated and rapidly decreased after removal of responsible tumors for TIO. These
      results confirm that FGF-23 is a causative factor of TIO and indicate that
      measurement of FGF-23 is useful for diagnosis and management of TIO. Moreover,
      FGF-23 levels were elevated in most patients with XLH suggesting FGF-23 is also
      involved in the pathogenesis of XLH. Further analysis is required to clarify more
      detailed actions of FGF-23 and its roles in the development of other diseases
      with disordered phosphate metabolism.

PMID- 14968561
TI  - [Development of the cookie test for the early detection and analyses of metabolic
      risk factors of the life style related diseases and its significance].
AB  - While with toleranG 30% of the healthy subjects showed reactive hypoglycemia(2 h
      BS below 80 mg/dl) with symptoms, with cookie tests none showed hypoglycemia nor
      adverse effect. In National Cardiovascular Center, the rate of reactive
      hypoglycemia was 4.1% and in those with 2 h BS below 50 mg was 0.5%. The
      incidence seemed to be various according to the insulin reserve of pancreatic
      beta-cells. In subjects with life style related disorder, additional
      abnormalities other than basal were revealed together with insulin
      resistance(AUCInsulin, AUCInsulin x AUCGlucose). In subjects with exercise habit,
      who exhibited lower energy expenditure at rest but higher VO2max, shwoed smaller
      increase of blood glucose and insulin above basal on cookie test, indicating
      increased insulin sensitivity. A new snack test in subjects without exocrine
      pancreatic disorder serves natural carbohydrate(75 g) and fat source(24 g). The
      test has less adverse effects, like reactive hypoglycemia. The test revealed
      glucose intolerance, diabetes, hyperinsulinemia, postprandial dyslipidemia and
      insulin resistance more efficiently than in the routinely performed OGTT (liquid
      glucose) or fat loading test.

PMID- 14968562
TI  - [Molecular-based diagnosis of thyroid carcinoma: germ-cell carcinogenesis and
      aspiration biopsy nucleic acid diagnosis(ABND)].
AB  - Recent data have shown the existence of specific changes in mRNAs in thyroid
      carcinomas. It has not been clarified, however, why these changes clearly
      distinguish benign tissues from carcinomas, while genomic alternation such as
      mutations in the RAS or P53 genes do not. Further, the widely believed
      hypothesis, multi-step carcinogenesis, does not explain some clinical and
      experimental evidence of thyroid carcinomas. Considering these facts, we propose
      a new idea for thyroid carcinogenesis called "germ-cell carcinogenesis", in which
      cancer cells are derived from the remnant of fetal thyroid germ
      cells(thyroblasts) instead of normal thyroid follicular cells. Utilizing such
      mRNAs, we have established a new method for preoperative molecular-based
      diagnosis of thyroid carcinomas, Aspiration Biopsy Nucleic Acid Diagnosis(ABND).
      ABND allows us to perform preoperative nucleic acid analyses of the tumors by
      extracting RNAs or DNAs from tumor cells obtained by fine needle aspiration
      biopsies(FNABs). Pathological diagnosis of thyroid follicular carcinoma is quite
      difficult, and the establishment of preoperative molecular-based diagnosis of
      follicular carcinoma has been long expected. We found that quantification of the
      trefoil factor 3(TFF3)/galectin-3 mRNA ratio in thyroid tumor cells is a useful
      tool for distinction between follicular adenomas and carcinomas. Because ABND can
      be performed without any severe invasion to the patients, in the near future,
      when more reliable systems of quantitative RNA analysis have been developed, ABND
      will probably become one of the standard tests for preoperative diagnosis of
      thyroid carcinoma.

PMID- 14968563
TI  - [Development of blood examination method of serum amyloid A and LDL complex, and
      clinical application to prediction of cardiovascular event].
AB  - In recent years, it has been reported that the acute-phase proteins C-reactive
      protein(CRP) and serum amyloid A(SAA), the sera levels of which are elevated in
      inflammation, are also elevated in coronary artery disease such as acute
      myocardial infarction. Also, high-sensitivity CRP assay is thought to be useful
      in predicting the prognosis of coronary heart disease. While investigating
      complexes of acute-phase proteins and low-density lipoprotein(LDL), we found a
      complex of LDL and SAA(SAA/LDL complex). The SAA/LDL complex in blood are formed
      from LDL and HDL by an oxidation reaction. Therefore, we developed an ELISA using
      anti-human SAA antibody and anti-human apoB, and determined a new method for
      measuring SAA/LDL complex in sera. We evaluated SAA/LDL complex as a new marker
      for prediction of prognosis in addition to the ordinary markers in consecutive
      140 patients with stable coronary heart disease who had at least 1 coronary
      artery stenosis more than 50% in diameter at the diagnostic coronary angiography.
      Of these 140 patients, 2 developed fatal myocardial infarction, 2 cerebral
      infarction, and 17 angina pectoris requiring coronary revascularization therapy
      during 1 year and 6 months after blood examinations. The SAA/LDL complex value in
      this EVENT group of 21 patients was significantly higher than that in the control
      group of 119 individuals. High-sensitivity CRP (hs-CRP) assay and SAA measurement
      showed no significant difference between the 2 groups. The SAA/LDL complex
      reflects intravascular inflammation directly and can be a new marker more
      sensitive than hs-CRP or SAA for prediction of prognosis in patients with stable
      coronary artery disease.

PMID- 14968565
TI  - [Diagnostic tests approved by Ministry of Health and Welfare (December 2003)].

PMID- 14968564
TI  - [Somatosensory evoked potentials/fields--exploration of brain function].
AB  - We have summarized the history of electroencephalography(EEG) since 1875, when a
      paper by Richard Caton was published describing the first EEG recordings in
      animals. Somatosensory evoked potentials (SEPs) were recorded by George Dawson in
      1951. Thereafter, SEPs were developed for clinical use with other evoked
      potentials such as auditory evoked potentials(VEPs). To understand evoked
      potentials, related mechanism of induction of far-fields-potentials(FFP)
      following stimulation of the median nerve has been discussed. SEPs consisted of
      P9, N9, N10, P11, N11, N13, P13, P14, N18, N20 and P20/P22. Scalp recorded P9 FFP
      arises from the distal portion of the branchial plexus as reflected by N9
      stationary negative potential recorded over the stimulated arm. Cervical N11 and
      N13 arise from the root entry zone and dorsal horn, respectively. Scalp recorded
      P13, P14 and N18 FFP originate from the brainstem. In this communication,
      magnetoencephalography(MEG) and results of one of our recent studies on
      somatosensory evoked fields(SEFs) are also discussed. One of the important
      features of MEG is that magnetic signals detected outside the head arise mainly
      from cortical currents tangential to the skull. Since the net postsynaptic
      current follows the orientation of cortical pyramidal cells, the MEG signals
      mainly reflect activity of the fissural cortex, whereas radial current may remain
      undetected. In our study, we demonstrated SEFs elicited by compression and
      decompression of a subject's glabrous skin by a human operator. Their dipoles
      were tangentially oriented from the frontal lobe to parietal lobe.

PMID- 14968566
TI  - [Present status of pancreatic diseases in Japan].

PMID- 14968567
TI  - [Evidence-based clinical guidelines for acute pancreatitis in Japan].

PMID- 14968568
TI  - [Evidence-based clinical guidelines for acute pancreatitis--diagnosis of the
      severity].

PMID- 14968569
TI  - [Evidence-based therapeutic guidelines for acute pancreatitis].

PMID- 14968570
TI  - [Evidence-based therapeutic guidelines for severe acute pancreatitis].

PMID- 14968571
TI  - [Clinical symptoms and diagnostic standards in chronic pancreatitis].

PMID- 14968572
TI  - [Etiology and physiopathology of chronic pancreatitis].

PMID- 14968573
TI  - [Therapy for chronic pancreatitis and the prognosis].

PMID- 14968574
TI  - [Therapeutic management for complications in chronic pancreatitis].

PMID- 14968575
TI  - [Diagnosis of pancreatic neoplasms].

PMID- 14968576
TI  - [Conservative therapy for pancreatic cancer].

PMID- 14968577
TI  - [Surgical therapy for pancreatic neoplasms].

PMID- 14968578
TI  - [Diagnosis of and therapy for endocrine tumors of the pancreas].

PMID- 14968579
TI  - [Hereditary pancreatitis].

PMID- 14968580
TI  - [Autoimmune pancreatitis].

PMID- 14968581
TI  - [Mucinous cystic tumor and intraductal papillary-mucinous tumor of the pancreas].

PMID- 14968582
TI  - [Progress in endoscopic therapy for pancreatic diseases].

PMID- 14968583
TI  - [Present status and progress in diagnosis of and therapy for pancreatic disease
      (discussion)].

PMID- 14968584
TI  - [Malignant rheumatoid arthritis in the young with polyneuritis as an initial
      symptom].

PMID- 14968585
TI  - [Right oculomotor nerve palsy due to juvenile neurosyphilis].

PMID- 14968586
TI  - [Primary plasma cell leukemia (IgD-lambda) with hyperammonemia].

PMID- 14968587
TI  - [Intravenous leiomyomatosis extending into the right atrium from a myoma of the
      uterus].

PMID- 14968588
TI  - [Obesity hypoventilation syndrome (OHS) successfully treated with non-invasive
      positive pressure ventilation (NIPPV)].

PMID- 14968589
TI  - [Multiple jejunal cancer diagnosed as a consequence of severe anemia].

PMID- 14968590
TI  - [Amebic liver abscess with panperitonitis treated successfully with intravenous
      injection of metronidazole].

PMID- 14968591
TI  - [Therapeutic efficacy and the adverse effects of newly developed biological
      agents for rheumatoid arthritis].

PMID- 14968592
TI  - [Progress in neurogastroenterology].

PMID- 14968593
TI  - [New therapeutic agents for chronic hepatitis C].

PMID- 14968594
TI  - [Evidence-based medicine and treatment outcome].

PMID- 14968595
TI  - [Intraoperative coronary spasm in non-cardiac surgery].
AB  - BACKGROUND: Cardiovascular events are one of the most critical perioperative
      complications. The purpose of this study is to investigate the clinical
      characteristics, effective treatments, and clinical outcome of intraoperative
      coronary spasm through a review of the published literature. METHODS: Reports of
      intraoperative coronary spasm were identified using the Medline database (1977
      2000) or by manually searching the Journal of Anesthesia (1987-2000). The
      clinical characteristics of intraoperative coronary spasm were analyzed in the 56
      patients who had developed coronary spasm during non-cardiac surgery. RESULTS:
      The mean patient's age was 58 +/- 13 years. The majority of patients were men
      (75%), Japanese (78%), and had no history of chest pain (75%). Regional
      anesthesia, vasopressors, alkalosis, hypotension, inadequate depth of anesthesia,
      and vagal stimulation were noted as major contributing factors. More than half of
      the patients showed severe hypotension and 30% developed cardiovascular collapse.
      However, coronary dilators, and nitrates in particular, were very effective for
      the treatment, and the clinical outcome was relatively good (one death and three
      cases of myocardial infarction). CONCLUSIONS: Intraoperative coronary spasm may
      develop in patients with no history of chest pain. Some of the intraoperative
      conditions themselves are potent vasoconstricting factors. Once coronary spasm
      occurs, immediate administration of a full dose of coronary dilators is
      recommended.

PMID- 14968596
TI  - [Intravenous fluid administration and management of body temperature].
AB  - Hypothermia occurs due to body heat redistribution between core and peripheral
      tissues as well as imbalance between heat loss and production. Perioperative
      hypothermia not only induces offensive shivering and prolongation of anesthetic
      recovery but also increases blood loss and incidence of surgical wound infection,
      increasing postoperative morbidity. It has been shown that intraoperative
      intravenous fluid administration and blood product transfusion have considerable
      effects on body temperature. Thus, it is important to monitor and control the
      temperature of fluids. Anesthesiologists should have knowledge of the
      characteristics of the various kinds of fluid warmer currently available and use
      them appropriately according to surgical procedures and the patient's position.
      It was reported recently that administration of amino acid can prevent
      intraoperative hypothermia, possibly by increasing the heat production in the
      body.

PMID- 14968597
TI  - [Inducible nitric oxide synthase gene expression induced by moderate hypoxia in
      the rat left ventricular myocardium].
AB  - BACKGROUND: Moderate hypoxia might influence the induction of nitric oxide
      synthase (iNOS) messenger RNA (mRNA) expression in the rat left ventricular
      myocardium. METHODS: Seventy-two Sprague-Dawley rats were divided into two groups
      as follows: 1) those with controlled ventilation with air (n = 36), and 2) those
      with controlled ventilation with 10% oxygen as a hypoxic group (n = 36). Heart
      rate (HR) and mean arterial pressure (MAP) were measured during the study.
      Before, and 2, 4, 6, 8, or 10 hr after, inhalation of air or 10% oxygen (6 rats
      for each time), thoracotomy was performed and the left ventricular myocardium was
      removed. Total RNA was assayed by the reverse transcription-polymerase chain
      reaction (RT-PCR) with gene-specific primers for iNOS and glyceraldehyde-3
      phosphate dehydrogenase. RESULTS: In the air group, there were no significant
      differences in HR, MAP, and the level of iNOS mRNA throughout the study. In the
      hypoxic group, however, HR and MAP decreased significantly from 4 and 6 hr after
      inducing hypoxia, respectively. The level of iNOS mRNA increased significantly
      from 2 through 10 hr after inducing hypoxia. CONCLUSIONS: This study demonstrated
      that in the rat left ventricular myocardium, iNOS mRNA expression increased from
      2 hr after inducing hypoxia, and seemed to increase concomitantly with longer
      duration of hypoxia.

PMID- 14968598
TI  - [The effects of patient-controlled epidural analgesia with background infusion
      after abdominal surgery].
AB  - BACKGROUND: Although patient-controlled epidural analgesia (PCEA) is widely known
      to provide good pain control after abdominal surgery, it has not been popular in
      Japan. We evaluated the effects of PCEA with background infusion after major
      abdominal surgery. METHODS: Ninety patients scheduled for abdominal surgery were
      randomly allocated to two groups by treatment with postoperative epidural
      analgesia: infuser group (n = 48); continuous infusion 5 ml.hr-1 or PCEA group (n
      = 42); background infusion 5 ml.hr-1, PCEA 3 ml and lock out 30 min. Microject
      (Sorenson Medical Co, U.S.A.) was used for PCEA machine. 0.2% ropivacaine 100 ml
      with fentanyl 500 micrograms was administered into the epidural space in both
      groups. RESULTS: Postoperative visual analogue scale (VAS) at rest and coughing
      were about 10 mm and 40 mm in both group, respectively, and there were no
      significant differences between the groups. NSAIDs were effective for rescue
      analgesia in infuser group to improve postoperative pain as PCEA. Vomiting and
      sedation were more frequent in infuser group than in PCEA group. Empty battery
      and machine troubles of unknown origin were observed in 2 and 4 patients,
      respectively in PCEA group. CONCLUSIONS: PCEA with background infusion could
      improve the management of postoperative pain, and adequate program of PCEA is
      important to reduce postoperative pain and its side effects.

PMID- 14968599
TI  - [The effect of inhalation induction with sevoflurane on left ventricular systolic
      and diastolic function. A transthoracic echocardiographic study].
AB  - BACKGROUND: The effect of inhalation induction with sevoflurane on left
      ventricular(LV) function has not been evaluated in adults. We assessed the effect
      of inhalation induction with sevoflurane on left ventricular systolic and
      diastolic function in adult patients using transthoracic echocardiography.
      METHODS: Twenty-five patients (ASA 1-2 and age < 70 years) received inhalation
      induction with 5% of sevoflurane. LV systolic function was evaluated by
      fractional shortening (FS), ejection fraction (EF), rate-corrected mean velocity
      of circumferential fiber shortening (Vcfc) and a contractile index, LV end
      systolic wall stress (ESWS) versus Vcfc relation (ESWS-Vcfc relation). LV
      diastolic function was assessed by analysis of transmitral flow velocity, peak
      early diastolic and late diastolic filling velocities (E wave and A wave), E/A
      ratio and E wave deceleration time (DT). RESULTS: After induction, sevoflurane
      caused significant decreases in FS, EF, Vcfc, ESWS-Vcfc relation, E wave, and A
      wave, and a significant increase in E/A and maintained DT. CONCLUSIONS: During
      inhalation induction with sevoflurane in adult patients, sevoflurane caused
      negative inotropic effects, but preserved LV diastolic function.

PMID- 14968600
TI  - [Two cases of pulmonary hypertension crisis in patients with primary pulmonary
      hypertension].
AB  - Primary pulmonary hypertension (PPH) is an uncommon disease. We describe two
      cases of pulmonary hypertension crisis in patients with PPH during general
      anesthesia. Any factor that worsens primary pulmonary hypertension (strain,
      hypoxia, pain, hypercapnia, intubation, or hyperinflation) should be avoided.

PMID- 14968601
TI  - [Does electromagnetic interference not occur to a bipolar pacemaker during TUR
      P?].
AB  - It has been reported that a unipolar pacemaker is more sensitive to
      electromagnetic interference (EMI) than a bipolar pacemaker. However, we
      experienced cases in which electrosurgery device interfered with a bipolar
      pacemaker, but not with a unipolar pacemaker during TUR-P. It has been suggested
      that EMI occurs to a bipolar pacemaker depending on sensitivity and electric
      resistance of a patient.

PMID- 14968602
TI  - [Intraoperative coronary spasm in patients without a history of anginal chest
      pain].
AB  - We report three cases of intraoperative coronary spasm that developed during non
      cardiac surgical procedures. None of the patients had a history of anginal chest
      pain. The presumed contributing factors were: 1) suction of the trachea during
      general anesthesia, 2) hyperventilation and hypotension during induction of
      general anesthesia, and 3) hyperventilation during neuroanesthesia. Coronary
      vasodilators were administered and all cases recovered promptly without any
      clinical sequelae. A review of the literature reveals that the majority of
      patients who developed intraoperative coronary spasm had no history of anginal
      chest pain. Some of common intraoperative conditions such as hyperventilation,
      hypotension, and inadequate depth of anesthesia, were reported to be potent
      precipitating factors for coronary spasm. In recent years, a larger proportion of
      surgical patients have coronary risk factors. Careful anesthetic management is
      required to prevent intraoperative coronary spasm even in patients without a
      history of coronary artery disease.

PMID- 14968603
TI  - [Anesthetic management of a patient with olivopontocerebellar atrophy using heart
      rate variability (HRV)].
AB  - A 65-year-old woman with olivopontocerebellar atrophy (OPCA), manifested with
      cerebellar ataxia mainly, with coexisting impairment of the autonomic nervous
      system function, and extrapyramidal symptoms, was scheduled for cholecystectomy.
      With no premedication, anesthesia was induced with sevoflurane and maintained
      with 1-1.5% of sevoflurane and 66% of nitrous oxide mixed with oxygen. Heart rate
      variability (HRV) calculated from ECG was used for a monitor of the autonomic
      nervous system activity. Before the induction of anesthesia, severe reduction of
      the HRV parameters suggested that both her sympathetic and parasympathetic
      nervous activities might have been severely reduced. We considered that the
      patient might have postganglionic sympathetic nerve hypersensitivity against
      inotropic agents. When her blood pressure decreased temporarily after the
      induction of anesthesia, a bolus dose of ephedrine 1 mg wa given intravenously,
      which stimulated the sympathetic nervous system indirectly, and could increase
      her blood pressure. Hypotension during anesthesia in a patient with OPCA with
      severe autonomic nervous failure was successfully treated by a minimal dose of
      ephedrine.

PMID- 14968604
TI  - [Coronary artery spasm during cholecystectomy with pneumoperitoneum--a case
      report].
AB  - A 59-year-old man without a history of ischemic heart disease underwent elective
      laparoscopic cholecystectomy under general anesthesia with epidural anesthesia.
      About 15 min after pneumoperitoneum had been achieved, the patient developed ST
      elevation and hypotension. Vagal stimulation resulting from stretching
      peritoneum, the procedure and epidural anesthesia are thought to have induced
      vasospasm. The ST segment became normal after interruption of CO2 insufflation. A
      postoperative coronary artery angiogram showed normal coronary arteries, but
      diffuse coronary artery spasm was seen after intracoronary injection of
      acetylcholine. The patient was discharged on nitrates. Patients with gall bladder
      stones sometimes have coronary risk factors of obesity, hyperlipidemia and
      hyperglycemia. Careful attention should also be given to patients who do not have
      a history of coronary disease.

PMID- 14968605
TI  - [Anesthetic management of a patient with single atrium and single ventricle].
AB  - A 41-year-old woman with single atrium and single ventricle at 6 weeks of
      gestation was scheduled for dilation and evacuation of the fetus. The PaO2 was 39
      mmHg, while she was breathing room air. Dilatation of the uterine cervical canal
      was performed under spinal anesthesia using 2.0 ml of 0.5% hyperbaric bupivacaine
      one day before dilatation and evacuation of the fetus. A sensory anesthesia level
      of T 10-S 5 was achieved. The systolic blood pressure decreased to around 70
      mmHg. On the next day, dilation and evacuation of the fetus was performed under
      spinal anesthesia using 1.5 ml of 0.5% isobaric bupivacaine. Sensory anesthesia
      level was L 1-S 5. There was no precipitous decrease in blood pressure. However,
      intravenous fentanyl was needed during the procedure. There was no cardiovascular
      or respiratory complication after anesthesia and surgery. The patient was
      discharged on the next day.

PMID- 14968606
TI  - [Regional anesthesia for a patient with stiff-person syndrome].
AB  - We report a case of stiff-person syndrome (SPS). A 65-year-old male underwent an
      emergency pacemaker implantation for syncope. With lidocaine infiltration under
      fentanyl and propofol sedation, the operation was completed without
      complications. Muscle rigidity and spasms are exacerbated by sensory and
      emotional stimuli in SPS. However, the present case suggests that regional
      anesthesia is also acceptable under adequate sedation.

PMID- 14968607
TI  - [Single lung ventilation in a pediatric patient using a Fogarty catheter with a
      hollow center].
AB  - A six-year-old boy with left pulmonary segmentation was scheduled for video
      assisted thoracoscopic left lower lobectomy. Because he had had repeated
      pneumonia, and the operation needed good surgical visualization, we used a 4 Fr
      Fogarty catheter with a hollow center (Fogarty Thru-Lumen Embolectomy: Baxter) as
      a bronchial blocker for one-lung ventilation. The Fogarty catheter was advanced
      to the left mainstem bronchus through the 5.5 mmID standard tube under direct
      view with a fiberscope. The one lung anesthesia was successfully performed. We
      could easily deflate the lung and drain the blood and sputum from the blocked
      lung. Postoperatively, there was no evidence of atelectasis of the lungs. The
      post-operative course was uneventful. The Fogarty catheter with a hollow center
      is useful for one lung anesthesia for pediatric patients. It is easy to insert
      and fix. And, we can easily deflate and drain the blocked lung.

PMID- 14968608
TI  - [Postintubation granuloma of the larynx].
AB  - A 50-year-old woman underwent tonsillectomy under general anesthesia. She
      developed progressive hoarseness two month after the tonsillectomy, and a large
      granuloma of the larynx was found. Surgical removal of the granuloma was
      performed by laryngo-microsurgery. We should keep in mind that postintubation
      granuloma of the larynx might develop after tracheal intubation, and careful
      airway manipulation is needed to avoid this potential complication.

PMID- 14968609
TI  - [Transient increase of bispectral index in a patient with bronchoconstriction
      after endotracheal intubation].
AB  - A 62-year-old woman (148 cm, 48.5 kg) with a history of bronchial asthma
      underwent an emergency appendectomy. Ten days before the operation she developed
      symptoms of wheezing while under asthma medication. An endotracheal tube (7 mm)
      was inserted after the induction of general anesthesia with intravenous injection
      of fentanyl 100 micrograms, propofol 100 mg and vecuronium 10 mg under Sellick's
      maneuver. Anesthesia was maintained with 1% sevoflurane with oxygen 6l-min-1 just
      after intubation, but bilateral lung sound soon became weaker and ventilation
      difficult. Based on a diagnosis of bronchoconstriction, we started
      hyperventilation with 3% sevoflurane. Ventilation returned to normal after about
      5 minutes. Percutaneous O2 saturation was maintained at 100% during this episode,
      but the BIS transiently rose to 82. Anesthesia was maintained with 2% sevoflurane
      and 50% nitrous oxide balanced with oxygen, and 250 mg aminophylline was
      administered. Upon completion of the operation, the endotracheal tube was removed
      without any events. The patient gave no sign of awareness during the operation.
      When severe bronchoconstriction prevents the absorption of anesthetics from the
      lung alveoli, additional intravenous anesthetics should be administered to
      maintain stable amnesia.

PMID- 14968610
TI  - [Tracheal intubation using a guide wire for a 5-month-old baby with epiglottic
      cyst].
AB  - We report anesthetic management for a 5-month-old baby with an epiglottic cyst
      causing stenosis of the upper airway and growth failure. A flexible guide wire
      was first inserted into the trachea through the forceps port of the fiberoptic
      bronchoscope (O.D. 3.5 mm) nasally. After removal of the bronchoscope, the
      trachea was then successfully intubated with a trachea tube (I.D. 3.5 mm) passed
      over it. Her symptom improved after removal of the cyst. A flexible guide wire
      combined with fiberoptic bronchoscope is useful in tracheal intubation for a baby
      with a difficult airway.

PMID- 14968611
TI  - [Anesthetic management of a hemodialysis-dependent patient for the brain tumor
      resection with CHDF].
AB  - A 64-year-old man was scheduled for resection of brain tumor in the prone
      position. He had been on hemodialysis for three years. Anesthesia was induced
      using propofol, fentanyl, and vecuronium, and maintained with isoflurane and
      nitrous oxide in oxygen. Transesophagial echocardiography (TEE) was useful for
      maintaining fluid balance. To prevent bleeding tendency and to maintain
      electrolyte balance, continuous hemodiafiltration (CHDF) without anti-coagulant
      drugs was utilized for fluid management. Surgery was performed in the lateral
      position since the application of CHDF was impossible in the prone position.
      Approximately 3500 ml of blood was lost and 18 units of packed blood cells and 18
      units of flesh frozen plasma were administered. We occasionally checked activated
      clotting time and platelet count during surgery, but they were kept in normal
      ranges. In this case, we were able to achieve proper intraoperative fluid
      management using TEE and CHDF.

PMID- 14968612
TI  - [Lever type push-pull device for ACD-CPR].
AB  - Prolonged use of the CardioPump can cause fatigue and may impair performing the
      ACD-CPR maneuver accurately. We applied a lever mechanism to lessen the fatigue.
      The fixed part of the lever consists of a 40 cm metal pipe, 2 cm in diameter,
      mounted vertically to a rectangular metal base plate (45 cm x 20 cm) placed under
      the patient when the device is used. The fulcrum of the lever is positioned at
      any height on the vertical tube. One end of the 65 cm lever was connected to a
      pin-joint hub at the fulcrum. The height of the fulcrum is adjusted for each
      patient according to the anterior-posterior dimension of the thorax. The Cardio
      Pump is mounted in a frame which is movable along the shaft of the lever between
      the fulcrum and the handle at the operator end of the lever. ACD-CPR is performed
      by lowering and raising the handle. The range of motion is controlled for safety
      by observing the movement of the chest wall of the patient from the side. We were
      able to maintain ACD-CPR with this device for more than 30 minutes without
      significant fatigue.

PMID- 14968613
TI  - From smallpox to SARS: is the past prologue?

PMID- 14968614
TI  - From public health to population health: how law can redefine the playing field.

PMID- 14968615
TI  - Public health law: the values of global collaboration.

PMID- 14968616
TI  - Are we prepared for tomorrow's health challenges?

PMID- 14968617
TI  - Workshop on smallpox legal preparedness: what have we learned from smallpox legal
      preparedness?

PMID- 14968618
TI  - Symposium on public health law surveillance: the nexus of information technology
      and public health law.

PMID- 14968619
TI  - Legal preparedness for public health emergencies: TOPOFF 2 and other lessons.

PMID- 14968620
TI  - Public health preparedness and the law in communities of color.

PMID- 14968621
TI  - Approaches to implementing the Olmstead ADA (Americans with Disabilities Act)
      ruling.

PMID- 14968622
TI  - The challenge of for-profit health care conversions.

PMID- 14968623
TI  - The role of law in health services delivery: diabetes and state-mandated
      benefits.

PMID- 14968624
TI  - New pressures/new partnerships: public health and law enforcement.

PMID- 14968625
TI  - When public health meets the judiciary.

PMID- 14968626
TI  - Health care and public health lawyers: reclaiming the historical role.

PMID- 14968627
TI  - Should your state have a public health law center?

PMID- 14968628
TI  - New directions in health insurance design: implications for public policy and
      practice.

PMID- 14968629
TI  - Quarantine in severe acute respiratory syndrome (SARS) and other emerging
      infectious diseases.

PMID- 14968630
TI  - Using science-based guidelines to shape public health law.

PMID- 14968631
TI  - Applying the regulatory powers of public health.

PMID- 14968632
TI  - The HIPAA Privacy Rule: reviewing the post-compliance impact on public health
      practice and research.

PMID- 14968633
TI  - School-based policies: nutrition and physical activity.

PMID- 14968634
TI  - The role of non-governmental organizations (NGOs) in public health law.

PMID- 14968635
TI  - Land use and zoning for the public's health.

PMID- 14968636
TI  - Who will keep the public healthy? Assuring a legally prepared workforce.

PMID- 14968637
TI  - Preemption in public health: the dynamics of clean indoor air laws.

PMID- 14968638
TI  - New developments in public health case law.

PMID- 14968639
TI  - Using the turning point model state public health law.

PMID- 14968640
TI  - Workshop on public health law and ethics I & II: The challenge of public/private
      partnerships (PPPs).

PMID- 14968641
TI  - New directions for health insurance design: implications for public health policy
      and practice.
AB  - National attention on issues of public health preparedness necessarily brings
      into sharp focus the question of how to assure adequate, community-wide health
      care financing for preventive, acute care, and long-term medical care responses
      to public health threats. In the U.S., public and private health insurance
      represents the principal means by which medical care is financed. Beyond the
      threshold challenge of the many persons without any, or a stable form of,
      coverage lie challenges related to the structure and characteristics of health
      insurance itself, particularly the commercial industry and its newly emerging
      market of consumer-driven health plans. States vary significantly in how they
      approach the regulation of insurance and in their willingness to support various
      types of insurance markets. This variation is attributable to the size and
      robustness of the insurance market, the political environment, and regulatory
      tradition and custom. Reconciling health insurance markets with public health
      related health care financing needs arising from public health threats should be
      viewed as a major dimension of national health reform.

PMID- 14968642
TI  - Public health ethics: the voices of practitioners.
AB  - Public health ethics is emerging as a new field of inquiry, distinct not only
      from public health law, but also from traditional medical ethics and research
      ethics. Public health professional and scholarly attention is focusing on ways
      that ethical analysis and a new public health code of ethics can be a resource
      for health professionals working in the field. This article provides a
      preliminary exploration of the ethical issues faced by public health
      professionals in day-to-day practice and of the type of ethics education and
      support they believe may be helpful.

PMID- 14968643
TI  - Making food safety an issue: internationalized food politics and French public
      health from the 1870s to the present.

PMID- 14968644
TI  - To stamp out "so terrible a malady": bovine tuberculosis and tuberculin testing
      in Britain, 1890-1939.

PMID- 14968645
TI  - Diocesan licensing and medical practitioners in south-west England, 1660-1780.

PMID- 14968646
TI  - A pauper dead-house: the expansion of the Cambridge anatomical teaching school
      under the late-Victorian poor law, 1870-1914.

PMID- 14968647
TI  - Wellcome home to the Wellcome Foundation Archive.

PMID- 14968648
TI  - Frederic Lawrence Holmes 1932-2003.

PMID- 14968650
TI  - Emerging issues in population health: national and global perspectives. A tribute
      to Gene W. Matthews.

PMID- 14968651
TI  - Foreword. Public health law, 2002-2003: year of achievement.

PMID- 14968652
TI  - SARS: political pathology of the first post-Westphalian pathogen.

PMID- 14968653
TI  - Partners: discernment and humanitarian efforts in settings of violence.

PMID- 14968654
TI  - War, terrorism, and public health.

PMID- 14968655
TI  - When terrorism threatens health: how far are limitations on human rights
      justified.

PMID- 14968656
TI  - Health policy and the WTO.

PMID- 14968657
TI  - International trade, law, and public health advocacy.

PMID- 14968658
TI  - Public health and the built environment: historical, empirical, and theoretical
      foundations for an expanded role.

PMID- 14968659
TI  - Technologies to detect concealed weapons: fourth amendment limits on a new public
      health and law enforcement tool.

PMID- 14968660
TI  - "The king of terrors" revisited: the smallpox vaccination campaign and its
      lessons for future biopreparedness.

PMID- 14968661
TI  - Finding a way through the hospital door: the role of EMTALA in public health
      emergencies.

PMID- 14968662
TI  - New hope for victims of prison sexual assault.

PMID- 14968663
TI  - Populations and the law: the changing scope of health policy.

PMID- 14968664
TI  - Dealing with Humpty Dumpty: research, practice, and the ethics of public health
      surveillance.

PMID- 14968665
TI  - The myth of exceptionalism: the history of venereal disease reporting in the
      twentieth century.

PMID- 14968666
TI  - Applying the common rule to public health agencies: questions and tentative
      answers about a separate regulatory regime.

PMID- 14968667
TI  - The role of state law in protecting human subjects of public health research and
      practice.

PMID- 14968668
TI  - Health information privacy and public health.

PMID- 14968670
TI  - Forensic epidemiology: law at the intersection of public health and criminal
      investigations.

PMID- 14968669
TI  - What is public health legal preparedness?
AB  - Legal preparedness has gained recognition as a critical component of
      comprehensive public health preparedness for public health emergencies triggered
      by infectious disease outbreaks, natural disasters, chemical and radiologic
      disasters, terrorism and other causes. Public health practitioners and their
      colleagues in other disciplines can prepare for and respond to such an event
      effectively only if law is used along with other tools. The same is true for more
      conventional health threats. At first glance, public health legal preparedness
      may appear to be only a matter of having the right laws on the books. On closer
      examination, however, it is as complex as the field of public health practice
      itself. Public health legal preparedness has at least four core elements: laws
      (statutes, ordinances, regulations, and implementing measures); the competencies
      of those who make, implement, and interpret the laws; information critical to
      those multidisciplinary practitioners; and coordination across sectors and
      jurisdictions. The process of improving public health legal preparedness has
      begun in earnest with respect to potentially massive public health emergencies.
      Elected officials, public health, legal, and law enforcement practitioners, and
      national security organizations have contributed to initial benchmarks for the
      core elements. A few gaps in legal preparedness have been identified in the
      context of exercises, actual public health emergencies, and through more general
      assessments of public health preparedness conducted by CDC and the Department of
      Justice. While a strong beginning has been made, this work is incomplete.
      Redoubled effort is needed to define practical, measurable benchmarks or
      standards of legal preparedness, to identify and correct shortcomings, and to
      review findings from regular exercises and actual public health emergencies.
      There is great value in having this work move forward on two converging tracks,
      one defined by states and localities acting on their own initiative and the other
      shaped by the federal government as informed by state and local experience. The
      TOPOFF and Dark Winter exercises exemplify the grounded, case-based approach that
      teaches practical lessons about benchmarks, gaps, and steps to improve public
      health's legal preparedness. It goes without saying that action on both tracks
      should be taken by collaboratives whose membership includes representatives of
      the many different communities integral to the design and application of laws
      that affect the health of the public and the effectiveness of the public health
      system itself. Consistent with the concept of a public health or population
      health system with which we began this paper, participants in both tracks should
      include representatives of non-governmental bodies--community-based
      organizations, non-profit organizations active in disaster preparedness and
      response, and others. This paper presents a conceptual and analytic framework
      those groups may apply, one that is sufficiently broad to serve as an integrating
      schema across sectors and jurisdictions but also sufficiently flexible to
      accommodate the unique features of the many community and state public health
      systems which, together with federal partners, comprise the U.S. public health
      system, in sum, a framework responsive to the exigencies of our times, faithful
      to the guiding principles of American federalism, and conductive to a new
      standard of health protection for all our citizens.

PMID- 14968671
TI  - Public health literacy for lawyers.

PMID- 14968672
TI  - The Public Health Law Association: a new partnership in public health practice.

PMID- 14968673
TI  - The Turning Point Model State Public Health Act.

PMID- 14968674
TI  - New reproductive technologies and the inheritance rights of unborn children.

PMID- 14968675
TI  - Fast food fighters fall flat: plaintiffs fail to establish that McDonalds should
      be liable for obesity-related illnesses.

PMID- 14968676
TI  - Kentucky Association of Health Plans, Inc. v. Miller.

PMID- 14968677
TI  - Healthcare reimbursement: HMO arbitration clause enforced.

PMID- 14968678
TI  - Second Circuit permits state malpractice suit against HMO.

PMID- 14968679
TI  - Supreme Court limits permissible scope of government's ability to force
      medication of mentally ill defendants.

PMID- 14968680
TI  - Insurance recoupments.

PMID- 14968681
TI  - TMA on Capitol Hill: beyond the quick fix in 2004.

PMID- 14968682
TI  - Loss prevention case of the month. Monitoring remains critical.

PMID- 14968683
TI  - Here to help.

PMID- 14968684
TI  - Collagenous colitis treated successfully with budesonide.

PMID- 14968685
TI  - Hepatitis C and dilated cardiomyopathy.
AB  - In North America, viral infection is the most common cause of myocarditis. A
      number of common viral infections have been implicated. With the increased
      identification of patients with hepatitis C, there is recent evidence derived
      from myocardial molecular biology studies suggesting an association between HCV
      infection and the development of myocarditis. This may be followed by dilated
      cardiomyopathy. Primarily researchers overseas have supported the recognition of
      this association. We recently cared for a patient who appears to fulfill the
      clinical criteria of hepatitis C-induced cardiomyopathy.

PMID- 14968686
TI  - Right-sided heart thromboembolism and pulmonary embolism.
AB  - We report a patient with an evidence of bilateral calf deep vein thrombosis,
      hemodynamically significant pulmonary embolism, and echocardiographic evidence of
      right heart thromboemboli with "popcorn" appearance. She responded well to
      thrombolytics and low molecular weight heparin with resolution of symptoms and
      improvement of echocardiographic abnormalities.

PMID- 14968687
TI  - Neonatal adrenal failure due to congenital lipoid hyperplasia of cortex.

PMID- 14968688
TI  - Medicolegal aspects of sex reassignment surgery in Tennessee.

PMID- 14968689
TI  - Children's special services--providing services to families and children with
      special healthcare needs.

PMID- 14968690
TI  - The neural basis of predicate-argument structure.
AB  - Neural correlates exist for a basic component of logical formulae, PREDICATE(x).
      Vision and audition research in primates and humans shows two independent neural
      pathways; one locates objects in body-centered space, the other attributes
      properties, such as colour, to objects. In vision these are the dorsal and
      ventral pathways. In audition, similarly separable "where" and "what" pathways
      exist. PREDICATE(x) is a schematic representation of the brain's integration of
      the two processes of delivery by the senses of the location of an arbitrary
      referent object, mapped in parietal cortex, and analysis of the properties of the
      referent by perceptual subsystems. The brain computes actions using a few
      "deictic" variables pointing to objects. Parallels exist between such
      nonlinguistic variables and linguistic deictic devices. Indexicality and
      reference have linguistic and nonlinguistic (e.g., visual) versions, sharing the
      concept of attention. The individual variables of logical formulae are
      interpreted as corresponding to these mental variables. In computing action, the
      deictic variables are linked with "semantic" information about the objects,
      corresponding to logical predicates. Mental scene descriptions are necessary for
      practical tasks of primates, and preexist language phylogenetically. The type of
      scene descriptions used by nonhuman primates would be reused for more complex
      cognitive, ultimately linguistic, purposes. The provision by the brain's
      sensory/perceptual systems of about four variables for temporary assignment to
      objects, and the separate processes of perceptual categorization of the objects
      so identified, constitute a pre-adaptive platform on which an early system for
      the linguistic description of scenes developed.

PMID- 14968692
TI  - An examination of the impact of participation in a conversation group for
      individuals with a closed head injury.
AB  - This study describes the impact of participation in a conversational group for
      individuals with chronic closed head injury in the Department of Communication
      Pathology at the University of Pretoria over the period 1995-2000. The
      information was obtained through a combination of clinical observations by the
      writers; the examination of data from Pragmatic measures; and a Quality of Life
      Scale that was compiled and administered (to both the subjects and their
      significant others) examining the perceived effects of group therapy over time.
      The results showed that despite the plateauing of pragmatic competence over time,
      the impact of group therapy appeared to reveal itself in perceived improvements
      in social-communicative competence and quality of life by the subjects.
      Recommendation and suggestions were made for the refinement of the QOL Scale to
      more reliably measure the subjective perceptions of group members regarding the
      perceived value of group therapy. In addition to addressing future implications
      to move the conversation group forward, the results of the current study lead the
      authors to advocate the establishment of conversation groups for individuals with
      CHI who are suitable candidates.

PMID- 14968691
TI  - The comparative psychology of uncertainty monitoring and metacognition.
AB  - Researchers have begun to explore animals' capacities for uncertainty monitoring
      and metacognition. This exploration could extend the study of animal self
      awareness and establish the relationship of self-awareness to other-awareness. It
      could sharpen descriptions of metacognition in the human literature and suggest
      the earliest roots of metacognition in human development. We summarize research
      on uncertainty monitoring by humans, monkeys, and a dolphin within perceptual and
      metamemory tasks. We extend phylogenetically the search for metacognitive
      capacities by considering studies that have tested less cognitively sophisticated
      species. By using the same uncertainty-monitoring paradigms across species, it
      should be possible to map the phylogenetic distribution of metacognition and
      illuminate the emergence of mind. We provide a unifying formal description of
      animals performances and examine the optimality of their decisional strategies.
      Finally, we interpret animals' and humans' nearly identical performances
      psychologically. Low-level, stimulus-based accounts cannot explain the phenomena.
      The results suggest granting animals a higher-level decision-making process that
      involves criterion setting using controlled cognitive processes. This conclusion
      raises the difficult question of animal consciousness. The results show that
      animals have functional features of or parallels to human conscious cognition.
      Remaining questions are whether animals also have the phenomenal features that
      are the feeling/knowing states of human conscious cognition, and whether the
      present paradigms can be extended to demonstrate that they do. Thus, the
      comparative study of metacognition potentially grounds the systematic study of
      animal consciousness.

PMID- 14968693
TI  - The swallowing and voicing characteristics of pharyngeal dystonia: a single case
      report.
AB  - This paper describes the swallowing difficulty and abnormal voicing
      characteristics of a subject with pharyngeal dystonia. This rare form of
      dystonia, considered to be a neurological condition resulting in involuntary
      spasm of the muscles of the pharynx, has not been documented in terms of its
      effects on the acoustic properties of the voice. This study revealed that during
      pharyngeal spasm, there are significant delays in voice onset time, a reduction
      in fundamental frequency, an increased percentage of sub-harmonics and
      variability in the amplitude perturbation quotient as well as shimmer. There was
      also evidence of these characteristics during periods of 'spasm-free' voice
      production, suggesting that the condition might be more consistent than what the
      subject described. Resonance disturbances were observed in spasm, which might
      explain the 'hollow' and affected voice quality. The subject also reported severe
      swallowing difficulties during the periods of spasm, characterised by a tight
      constriction at the level of the subject's throat. It is clear that an
      abnormality at the level of the cricopharyngeal muscle has a dual effect on the
      acoustic properties of the voice and on swallowing.

PMID- 14968694
TI  - A transdisciplinary conceptual framework for the early identification of risks
      for communication disorders in young children.
AB  - The early identification of infants with communication disorders or at risk for
      communication delays is still one of the biggest challenges of early
      communication intervention (ECI) and threatens to compromise its efficacy.
      Current approaches to the early identification of young children at risk for
      communication disorders involve strategies aimed at the identification of general
      developmental delays and may not be sufficiently sensitive and specific enough to
      detect the early stages of communication disorders. The risks for mortality and
      health are often identified early in life, but the concomitant risks for
      communication disorders in the same young children are frequently not identified
      at that opportune time. The current study involved a descriptive survey,
      describing the identification of communication disorders in 153 subjects, whose
      data was stored in and retrieved from a customized ECI database system. The
      findings revealed that the subjects were assessed at the average age of 18
      months, but that identifications of risk conditions occurred prenatally, at
      birth, after the perinatal period and later in life. The time of identification
      related to the different communication disorders identified in the subjects and
      caregivers played a major role in detecting the first signs of communication
      disorders in their children. In order to provide a guideline for clinical
      practice, a transdisciplinary conceptual framework towards a coordinated effort
      for the early identification of risks for communication disorders in young
      children is proposed.

PMID- 14968695
TI  - Attitudes of children towards augmentative and alternative communication systems.
AB  - The purpose of this study was to determine the impact of voice output, as a
      characteristic of a child's AAC system, on the attitude of unfamiliar peers. The
      need to develop a suitable tool to measure the attitudes of peers led to the
      development of the Communication Aid/Device Attitudinal Questionnaire (CADAQ). A
      descriptive survey design was used and the suitability of the CADAQ was tested in
      a pilot study. One hundred and fifteen participants, aged 11-13 years, viewed a
      videotape of a 13-year-old boy with cerebral palsy, communicating with the use of
      an AAC device. Attitudes were measured according to three dimensions:
      affective/behavioural, cognitive/belief and communication competence. Data were
      analysed with a 2 (group) x 2 (gender) x 3 (dimension) analysis of variance
      (ANOVA) with infinity = .05. An item analysis, Cronbach Alpha's and scale
      intercorrelations between the 3 dimensions of the CADAQ were computed to
      determine the internal consistency of the CADAQ. Results reflected more
      favourable attitudes to the presence of voice output in comparison to the no
      voice option. Girls held more positive attitudes to the peer with disabilities
      and little or no functional speech (LNFS). Good internal consistency of the CADAQ
      was demonstrated.

PMID- 14968696
TI  - [Educational audiology: joint consultation in special eduation].
AB  - The aim of this study was to determine the value of educational audiology in the
      in-service training of teachers of children with hearing loss, in the South
      African context. Two questionnaires were developed which teachers and headmasters
      of schools for the deaf/hard of hearing in the Gauteng and Northwest provinces
      completed. The aim of the first questionnaire was to obtain background
      information regarding the 10 schools included in this study. The purpose of the
      second questionnaire was to determine the knowledge of 211 teachers regarding the
      child with a hearing loss. The background information obtained from the first
      questionnaire made it possible for the researchers to compare the knowledge of
      two different groups of teachers on the basis of in-service training. The results
      indicated definite limitations in the knowledge of the teachers, which must be
      viewed in light of the specific audiological needs of the child with a hearing
      loss, who may thus not fulfill his/her potential in the school setting. In spite
      of in-service training there was no significant difference between the two groups
      of teachers, which questions the value of existing training.

PMID- 14968697
TI  - The psychological effects of traumatic brain injury on the quality of life of a
      group of spouses/partners.
AB  - This study explored the psychosocial impact of traumatic brain injury on the
      perceived quality of life of a purposefully selected group of 14 spouses/partners
      of head injured persons by means of a self-administered questionnaire. Analysis
      of responses revealed that spouses/partners' altered communication patterns were
      perceived to have affected interpersonal relationships and quality of life
      extensively, indicating the need for speech-language therapy. Decreased income
      was noted due to the low incidence of return to work. Participants reported
      changes in family relationships, particularly between the injured person and
      their children as well as deterioration in marital relationships, suggesting the
      necessity for family therapy and marital counselling. Various emotional reactions
      were documented in response to injury. Yet most respondents expressed acceptance
      of their new roles and responsibilities despite the difficulties entailed. Since
      injured persons were dependent on their spouses/partners to a large extent, most
      of the latter reported feeling tied down. Loneliness predominated as a social
      consequence despite the support of pre-injury friendships. In terms of coping
      resources, friends, family, religion and support groups were perceived to be most
      effective. Results are discussed in terms of their clinical implications for
      psychosocial rehabilitation and spouse/partner counselling.

PMID- 14968698
TI  - Training, current practices and resources of a group of South African hospital
      based speech-language therapists and audiologists working with patients living
      with HIV/AIDS.
AB  - The present study employed a cross-sectional survey research design to
      investigate the training, current practices, and resources of a sample of South
      African hospital-based speech-language therapists and audiologists (SLTs & As)
      working with persons living with HIV/AIDS. Questionnaires were mailed to 50 SLTs
      & As working in the major provincial hospitals in Gauteng, Kwa Zulu Natal, Free
      State and Western Cape, and responses were obtained from 40 therapists. Data from
      the questionnaire were analyzed using descriptive statistics. The findings
      indicated that persons with HIV/AIDS were becoming an increasing part of the
      caseloads of the SLTs & As who were surveyed. Investigation of participants'
      training, knowledge, skills and confidence in the area of HIV/AIDS suggested that
      the group of SLTs & As surveyed did not perceive themselves to be adequately
      equipped to manage persons with HIV/AIDS. These findings highlight the need for
      improved undergraduate training of SLT & A students in the area of HIV/AIDS; more
      continuing professional development workshops on HIV/AIDS for qualified
      practitioners; better access to resources for SLTs & As working in the area; the
      formulation of a position statement on HIV/AIDS by SASLHA; and further research
      in this area.

PMID- 14968699
TI  - Auditory function in a group of adults infected with HIV/AIDS in Gauteng, South
      Africa.
AB  - Numerous international studies have demonstrated a relationship between HIV/AIDS
      and auditory function. The aim of this study was to explore this relationship in
      a group of adults infected with HIV/AIDS attending an outpatient clinic in a
      hospital located in Gauteng, South Africa. The prevalence of hearing loss; the
      type, degree and configuration of the hearing loss; the relationship between the
      hearing symptoms and the progressive stages of the disease, and the type of onset
      of hearing problems were examined. The results of the study indicated a
      prevalence rate of hearing loss which was as high as 23% in the sample surveyed.
      The types of hearing loss included conductive and sensorineural, while the degree
      of severity ranged from slight to profound in nature. The configuration of the
      hearing loss was not frequency-range-specific, and the degree of severity did not
      seem to worsen with the progression of the HIV/AIDS disease. However, there did
      seem to be an increase in the occurrence of sensorineural hearing loss with the
      deterioration of patients' immunological status. Analysis of patients'
      audiological results along with their case history data suggested that their
      hearing loss may have been caused by opportunistic infections and/or their
      treatments. These results are discussed in terms of their implications for the
      clinical management of patients with HIV/AIDS; education of team members; and
      policy formulation.

PMID- 14968700
TI  - Predicting hearing loss from otoacoustic emissions using an artificial neural
      network.
AB  - Normal and impaired pure tone thresholds (PTTs) were predicted from distortion
      product otoacoustic emissions (DPOAEs) using a feed-forward artificial neural
      network (ANN) with a back-propagation training algorithm. The ANN used a map of
      present and absent DPOAEs from eight DPgrams, (2f1-f2 = 406-4031 Hz) to predict
      PTTs at 0.5, 1, 2 and 4 kHz. With normal hearing as < 25 dB HL, prediction
      accuracy of normal hearing was 94% at 500, 88% at 1000, 88% at 2000 and 93% at
      4000 Hz. Prediction of hearing-impaired categories was less accurate, due to
      insufficient data for the ANN to train on. This research indicates the
      possibility of accurately predicting hearing ability within 10 dB in normal
      hearing individuals and in hearing-impaired listeners with DPOAEs and ANNs from
      500-4000 Hz.

PMID- 14968701
TI  - The iconicity of picture communication symbols for rural Zulu children.
AB  - The purpose of this study was to investigate the iconicity of selected Picture
      Communication Symbols (PCS) for rural Zulu ten-year-olds. Participants were
      presented with copies of a commercially available communication overlay without
      glosses. They were required to match a symbol with each of 36 spoken Zulu labels.
      With both strict and lenient scoring criteria applied, 2.8% and 11.1%
      (respectively) of the symbols on the communication overlay emerged as iconic for
      participants. It was further established that the position of symbols on the
      overlay, the total frequency of selection of symbols, and gender did not
      influence results. An analysis of errors revealed that for some symbols many of
      the participants agreed on a single specific label, be it the target label or a
      non-target label; while for other symbols there were either many possible labels,
      or none. The term distinctiveness was coined to describe how well defined or
      specific were the evoked meanings triggered by a symbol in the viewers' minds.
      Results suggest that participants did not make maximum use of the information
      provided by arrows in the symbols. This finding could be ascribed to the
      opaqueness of arrows and participants' lack of previous experience with these
      conventional cues in pictures, as well as the traditional oral nature of the Zulu
      culture.

PMID- 14968702
TI  - [Fluoride content of Swiss drinking water].
AB  - Fluoride contained in oral hygiene products plays a key role in the prevention of
      dental caries. Its efficacy is mainly due to a topical effect. Other possible
      sources of fluoride, with a systemic effect, are found in drinking water, table
      salt as well as food and drinks. It is important to consider all these various
      sources, including drinking water, in order to determine the total exposure to
      fluorides within a population. Water consumption may vary but its role cannot be
      neglected. The aim of this study was to collect data on the fluoride
      concentrations in drinking water in the different regions of Switzerland.
      Information was collected from the health authorities of each canton during a
      survey conducted between 1998 and 1999. The data showed that fluoride content in
      drinking water was low (< or = 0.3 mg/l) in the majority of the cantons. In
      nearly sixty localities, fluoride content was equal or above 0.5 mg/l: for 24
      wells, the fluoride concentration was between 0.5 mg/l and 0.7 mg/l; for another
      35 wells, fluoride content was > or = 0.7 mg/l.

PMID- 14968703
TI  - [Oral condition of abstaining alcoholics. A case-control study].
AB  - The aim of this study was to investigate the oral situation of long-term severely
      alcohol-addicted persons in a case-control-study. 28 controlled abstinent
      alcoholics and 30 control persons without any drinking history but who were
      smokers participated in the study. The mean age of the patients was 46 years, the
      alcohol addiction had existed for 17 years on average; the majority were heavy
      smokers with an average of two packs of cigarettes per day. The mean age of the
      control persons was 43 years, each of them smoked about one pack of cigarettes
      per day. The oral examination included the DMF-T and the different components,
      the QHI, the PBI and the CPI. Significant differences between the two groups were
      found for the following parameters: M-T (p < 0.0002), DMF-T and D-T (p < 0.002),
      PBI (p = 0.05). F-T and QHI revealed no differences. The periodontal examination
      showed that in 69% of the alcoholics and in 40% of the controls severe pocketing
      could be found (CPI 4). 4% of the patients and 20% of the controls had no
      periodontal pockets (CPI 0, 1 or 2). These results indicate that long-term
      severely alcohol-addicted persons have a high risk of periodontal breakdown and
      tooth loss. They also support the assumption that excessive consumption of
      alcohol may promote the progression of chronic periodontal disease.

PMID- 14968704
TI  - [Tissue engineering of autologous bone transplants. Possible indications and
      clinical use in implantology].

PMID- 14968705
TI  - [Medical emergencies in the dental office: contributions of continuing education.
      Enquiries among university centers of dentistry, sections of the SSO and private
      sources of continuing education in Switzerland].
AB  - Some dentists feel insecure in the management of medical emergencies as it has
      been pointed out in the SMfZ already. The focus on a national investigation by
      means of questionnaire was the training supply in emergencies as well as the
      course attendance by dentists. The results of this investigation proved, that
      about half of the dentists, practicing in Switzerland keep themselves more or
      less up-to-date. They know about the right measures in case of an accident that
      may put vital functions at risk. However, this investigation also showed that we
      know little or nothing about the other half of practicing dentists in our
      country. In the last part of the paper a project of an e-learning course on
      medical emergencies in the dental office is disclosed.

PMID- 14968706
TI  - [New treatments against AIDS: fusion inhibitors].

PMID- 14968707
TI  - [A new basis for treatment of chronic inflammatory diseases].

PMID- 14968708
TI  - [What's new in ketolides and oxazolidinones? Actions and resistance mechanisms].

PMID- 14968709
TI  - [How effective are linezolid and telithromycin? The resistance situation of
      pathogenic gram positive infections in Germany].

PMID- 14968710
TI  - [Two new antibiotics with special qualities: the pharmacokinetics of linezolid
      and telithromycin].

PMID- 14968711
TI  - [Action in nosocomial pneumonia and severe skin and soft tissue infections.
      Linezolid in treatment].

PMID- 14968712
TI  - [Importance in respiratory tract infections. Ketolides: clinical aspects].

PMID- 14968713
TI  - [Adverse effects of anti-infectives. Undesirable effects and interactions of
      ketolides and oxazolidonones].

PMID- 14968714
TI  - [And the path grows wider...ketolides and oxazolidinones in the pipeline].

PMID- 14968715
TI  - SARS in Singapore: looking back, looking forward.

PMID- 14968716
TI  - RUNX and cancer.

PMID- 14968717
TI  - Intrauterine stem cell therapy.

PMID- 14968718
TI  - Myogenic potential of fetal mesenchymal stem cells.

PMID- 14968719
TI  - Subjective versus observer-rated insight in first-episode psychosis in Singapore.

PMID- 14968720
TI  - Usefulness of serum soluble CD38 and CD157 levels in differentiating SLE, RA and
      healthy adults and their relationship with disease activity.

PMID- 14968721
TI  - Real-time quantitative polymerase chain reaction (RO-PCR) using the LightCycler:
      a rapid, high-throughput method for detecting and quantifying fusion transcripts
      in childhood leukaemias for disease stratification and prognostication.

PMID- 14968722
TI  - Angiomyogenesis using human myoblast carrying human VEGF165 for injured heart.

PMID- 14968723
TI  - Use of traditional medicine in an acute upper respiratory tract infection in
      Singapore.

PMID- 14968724
TI  - Fever phobia in a primary healthcare setting: a Singapore perspective.

PMID- 14968725
TI  - Revisiting upper respiratory tract infection (URTI) in adults in the light of the
      current severe acute respiratory syndrome (SARS) situation in Singapore.

PMID- 14968726
TI  - NF-kappa B plays a protective role in nitric oxide-induced neuronal apoptosis.

PMID- 14968727
TI  - Molecular monitoring of minimal residual disease in childhood acute lymphoblastic
      leukaemia using antigen receptor gene rearrangements is highly feasible for
      disease stratification and prognostication.

PMID- 14968728
TI  - Clinical features and predictors for mortality in a designated national SARS ICU
      in Singapore.

PMID- 14968729
TI  - Both gram positive and gram negative organisms complicate neutropaenic sepsis in
      children with leukemia. A unit audit study and recommendation.

PMID- 14968730
TI  - Ambulatory care of central venous Hickman's catheters can be successfully and
      safely carried out by parents at home: results of a patient education programme.

PMID- 14968731
TI  - Pain management at the emergency department--can we do better?

PMID- 14968732
TI  - Identification of factors influencing caregiving experience in caregivers of
      patients with schizophrenia.

PMID- 14968733
TI  - A prediction model to identify risk of developing Stevens-Johnson syndrome or
      toxic epidermal necrolysis in patients with erythema multiforme.

PMID- 14968734
TI  - Chinese version of patient rated wrist evaluation (PRWE): cross-cultural
      adaptation and reliability evaluation.

PMID- 14968735
TI  - Osteogenic role of vascular endothelial growth factor in bone regeneration.

PMID- 14968736
TI  - Evaluation of hemispheric language dominance in adult craniopagus twins with
      functional magnetic resonance imaging (fMRI).

PMID- 14968737
TI  - BRCA1 c.2845insA is a founder mutation in Singaporean Malay women with early
      onset breast/ovarian cancer.

PMID- 14968738
TI  - The effect of Mulligan Traction Straight Leg Raise in participants with short
      hamstrings.

PMID- 14968739
TI  - Prevalence, awareness and control of hypertension in community-dwelling elderly
      in Singapore.

PMID- 14968740
TI  - Allogenic stem cells transplantation in rabbit myocardial infarction.

PMID- 14968741
TI  - The effect of sialidase inhibitors on hyaluronan-mediated escape from apoptosis
      induced by anti-cancer drugs in gastric cancer.

PMID- 14968742
TI  - Blood-brain barrier disruption following traumatic brain injury: roles of tight
      junction proteins.

PMID- 14968743
TI  - Predictors of success in smoking cessation among hospitalised patients.

PMID- 14968744
TI  - Caregiver stress in activities of daily living-dependent elderly aged more than
      65 years.

PMID- 14968745
TI  - Interleukin-4 receptor alpha subunit (IL-4RA) gene polymorphisms and Singapore
      childhood minimal change disease.

PMID- 14968746
TI  - Comparative study of a two-year disease management programme for patients with
      diabetes in a primary healthcare setting.

PMID- 14968747
TI  - Tissue microarray study for classification of breast tumours.

PMID- 14968748
TI  - Clinical laboratory billing: superfluous requirements without justification?
AB  - Congress occasionally passes new laws that affect how clinical laboratories
      handle test orders from physicians and, subsequently, process the billing for
      tests. Once a bill is signed into law, it is forwarded to administrative
      agencies, which draft regulations and administrative procedures, under which the
      intentions of Congress are carried out. In the case of laboratory test ordering
      and billing, the Centers for Medicare and Medicaid Services (CMS) has the
      greatest influence over how these regulations and procedures are defined.
      Unfortunately, in many cases, billing rules have been promulgated in ways that
      create the need for hospitals and commercial laboratories to expend huge sums of
      money to bill within the confines of the administrative rules; cause clinical
      laboratories to suffer from omissions and mistakes of other parties who are part
      of the patient care process but are not accountable for the billing information
      they provide to laboratories; and, frankly, in some respects, simply defy common
      sense.

PMID- 14968749
TI  - Providing information at the point of care: educational diagnostic reports from a
      genetic testing service provider.
AB  - Strategies to facilitate the provisioning of genetic health-care services by
      primary care physicians will improve access to these services for the average
      patient while making the most efficient use of limited human and financial
      resources within the health-care system. Genetic laboratories have become a major
      source of information and consultation for clinicians ordering genetic tests.
      This article describes the development and evaluation of a program to provide
      physician-directed information from a molecular testing facility to assist
      physicians in selecting and counseling patients and interpreting genetic test
      results. Semi-structured telephone interviews were used to gather physicians'
      opinions about the utility of the program and the way in which the information
      was used in their practice. Forty-three percent of those interviewed were
      unfamiliar with some of the information provided, with test methodology and
      sensitivity/specificity most often identified as novel information. Fifty-two
      percent of pediatric specialists were unfamiliar with some aspect of the
      information Sheet, despite being the highest consumers of testing services in
      this sample. Pediatricians and pediatric specialists also rated the initiative
      highest in terms of its usefulness in their practice, followed by genetic
      specialists. Overall, physicians confirmed the utility of the program as an
      educational tool for themselves, and for other non-patient educational activities
      in which they are involved.

PMID- 14968750
TI  - Establishment of a central laboratory serum tumor marker service on a
      consolidated immunodiagnostic platform: development of practice standards,
      service improvements, and operational efficiency.
AB  - BACKGROUND: Laboratory testing for serum tumor markers traditionally has been
      performed in low volume in most hospitals. Many markers are sent out to reference
      laboratories. Over the past decade, serum tumor marker testing in patient
      management has become more defined, resulting in increasing test volume and wider
      availability of assays on automated immunodiagnostic platforms. METHODS: A
      retrospective review of laboratory operations, test volumes, and budgets over a
      10-year period. Results of utilization initiatives as part of a clinical practice
      management team also were reviewed. RESULTS: The volume of serum tumor marker
      requests in our institution increased 2.25-fold over an 8-year period. In
      contrast, total laboratory test volume increased only 1.3-fold. Implementation of
      an on-site tumor marker laboratory using a consolidated platform (Elecsys 2010)
      decreased the average unit cost per test from $12.36/test to $6.79/test. This was
      accomplished by a combination of insourcing and by consolidation of multiple semi
      automated instruments. Total savings were $219,972 per year, including direct
      budget reductions and cost avoidance due to volume increases. Various
      institutional practice standards were implemented, and turnaround time was
      markedly reduced for selected tests. CONCLUSIONS: Testing for serum tumor markers
      is becoming more established in large hospital laboratories. Increasing test
      volumes and the availability of consolidated instrument platforms with a broad
      menu of tumor marker tests (such as the Elecsys 2010) facilitates consolidation
      and insourcing of many tumor marker assays. This permits the laboratory to reduce
      unit and overall cost, to leverage excess capacity on existing instrumentation,
      and to create an opportunity to add value to the service by reducing turnaround
      time and implementing practice standards.

PMID- 14968751
TI  - To err is human: improving patient safety through failure mode and effect
      analysis.
AB  - Patient care errors occur in the laboratory. Traditionally, most errors have been
      thought to occur because of individual human failure. The assumption is that with
      adequate training, education; and orientation, technologists will perform
      flawlessly. Laboratory processes are designed on the premise that nothing will go
      wrong. Health-care professionals are looking at new methods of error prevention
      including Failure Mode and Effect Analysis (FMEA). Based on long experience in
      the engineering field, FMEA assumes everything will fail, humans err frequently,
      and the cause of an error often is beyond the individual's control. FMEA is a
      proactive, systematic, multidisciplinary team-based approach to error prevention.
      Patient safety is now a high priority with the Joint Commission on Accreditation
      of Healthcare Organizations, and this article introduces FMEA, a new method for
      improving our processes to enhance patient safety.

PMID- 14968752
TI  - A FMEA clinical laboratory case study: how to make problems and improvements
      measurable.
AB  - The authors have experimented the application of the Failure Mode and Effect
      Analysis (FMEA) technique in a clinical laboratory. FMEA technique allows: a) to
      evaluate and measure the hazards of a process malfunction, b) to decide where to
      execute improvement actions, and c) to measure the outcome of those actions. A
      small sample of analytes has been studied: there have been determined the causes
      of the possible malfunctions of the analytical process, calculating the risk
      probability index (RPI), with a value between 1 and 1,000. Only for the cases of
      RPI > 400, improvement actions have been implemented that allowed a reduction of
      RPI values between 25% to 70% with a costs increment of < 1%. FMEA technique can
      be applied to the processes of a clinical laboratory, even if of small
      dimensions, and offers a high potential of improvement. Nevertheless, such
      activity needs a thorough planning because it is complex, even if the laboratory
      already operates an ISO 9000 Quality Management System.

PMID- 14968753
TI  - Where are you going? The science of setting goals.
AB  - Picture this. You are at a workshop. Like most workshops, this one has
      interrupted your day and has taken you from more important tasks. Still, you are
      there. The presenter begins like this, "Good morning ladies and gentlemen Today,
      we will talk about setting goals!" You smirk and roll your eyes. "Been there,
      done that," you want to say. "I'm out of here!" You want to say. But you don't
      say; and you don't leave. So the presenter continues. "Here is a bow and arrow,"
      he says. "Who wants to make a million dollars with it?" You are glad you stayed.
      You can use a bow and arrow and you can use a million dollars. You stand up, take
      the bow and arrow from the presenter's hand and say "I'm in! What do I have to
      do?" "It's easy," says the presenter. "Just draw the bow and hit the bull's eye
      with your arrow. If you do, I'll give you one million dollars!" Your heart pounds
      and your eyes scan the room. This should be easy, but it's not because you can't
      find the bull's eye. "Hurry up," says the presenter "You've only got 10 seconds.
      Hit the bull's eye." You look again. Everywhere. Still no luck. Still no bull's
      eye. Still no million dollars. "Three seconds!" says the presenter. You are
      tense. You scream, "There is no bull's eye! How can I hit what isn't there?" "You
      can't!" says the presenter triumphantly. You can't hit what isn't there. That is
      what setting goals is all about!" You don't want to leave anymore.

PMID- 14968754
TI  - The learning department, Part two.
AB  - Whether you want to move deliberately toward becoming a learning department or
      not, the kind of organization that is described here is probably appealing and a
      little frightening. The staff is more self-reliant, there is a higher level of
      motivation, communication is more open, there is a dedication to continuous
      improvement, and there is more intentional, "smart" risk-taking. At the beginning
      of our last column ("The Learning Department, Part One"), we listed the five
      trends that we believe will shape the clinical laboratory of the future: 1.
      increased automation and the attendant reduction and shift in the technical
      skills required 2. chronic shortages of qualified staff 3. changes in the
      legislation that affects credentialing and regulation 4. expanded uses of
      molecular diagnostics 5. emergence of the lab as a major contributor to the
      hospital's bottom line. It is hard to imagine surviving these turbulent trends
      without instilling many of the characteristics of a learning department in your
      organization. What are the most important steps to take? Open communications,
      schedule debriefs to learn from your experiences, and stay curious!

PMID- 14968755
TI  - Advertising genetic testing for breast cancer.

PMID- 14968756
TI  - Common cent$ 16: risk!

PMID- 14968757
TI  - Learning a new language, Part two.

PMID- 14968758
TI  - Power to the people.

PMID- 14968759
TI  - Keeping waived tests simple.
AB  - Laboratories performing waived testing must follow the manufacturer's
      instructions as well as good laboratory practices to ensure that test results are
      reliable. Four things to concentrate on to maximize the performance and
      reliability of waived tests are to: 1. Read and follow the information found in
      the package inserts. 2. Follow the manufacturer's recommendations for running
      quality control. 3. Train staff members to perform tests correctly. 4. Follow
      established policies and procedures for patient testing in the practice.

PMID- 14968760
TI  - Saline infusion sonohysterography.
AB  - Saline infusion sonohysterography consists of ultrasonographic imaging of the
      uterus and uterocervical cavity, using real-time ultrasonography during injection
      of sterile saline into the uterus. When properly performed, saline infusion
      sonohysterography can provide information about the uterus and endometrium. The
      most common indication for sonohysterography is abnormal uterine bleeding.
      sonohysterography should not be performed in a woman who is pregnant or could be
      pregnant or in a woman with a pelvic infection or unexplained pelvic tenderness.
      Physicians who perform or supervise diagnostic saline infusion sonohysterograpy
      should have training, experience, and demonstrated competence in gynecologic
      ultrasonography and saline infusion sonohysterography. Portions of this document
      were developed jointly with the American College of Radiology and the American
      Institute of Ultrasound in Medicine.

PMID- 14968761
TI  - HIV-- tailored to fit.

PMID- 14968766
TI  - American society of hematology-45th annual meeting and exposition: hematological
      malignancies.

PMID- 14968768
TI  - American society of hematology-45th annual meeting and exposition symposia.

PMID- 14968778
TI  - Employment, starting salaries, and educational indebtedness of year-2003
      graduates of US veterinary medical colleges.

PMID- 14968779
TI  - [Advances in biochemical study of active anthraquinone constituents in Chinese
      traditional herb semen Cassiae].

PMID- 14968780
TI  - [Advances in the study on chemical constituents of Angelica dahurica].

PMID- 14968781
TI  - [Study on hypoglycemic action and active constituents of Momordica charantia L].

PMID- 14968782
TI  - [Primary hyperaldosteronism].

PMID- 14968783
TI  - Effect of beta-particles on the retinal chromophore in bacteriorhodopsin of
      Halobacterium salinarium.
AB  - Bacteriorhodopsin (bR) is an attractive intelligent material. Understanding the
      mechanism of its light-driven proton pumping outward the cell implicates it in
      many technical applications, particularly, in what is called optical computers,
      and the biotechnology is waiting for this promised biological molecule. An
      ionizing radiation source handling could be computerized in radiation fields. The
      computer containing such biological material will not be out of reach of the
      fields of ionizing radiation. So it is interesting to report on the working of
      such biological computer if it is subjected to ionizing radiation. The functional
      unit in this molecule is retinal chromophore. In the present work, it is
      interested to assess the functionality of bR through determining the electronic
      transition dipole moment of its chromophore. Significant changes in the values of
      the absorption transition dipole moment were noticed at different doses of beta
      particles in the range of 0.1-0.3 kGy. Ionizing radiation-induced changes in bR
      were followed by intrinsic fluorescence spectroscopy. An analysis of the
      fluorescence data bears on the tertiary structure of bR. The emission spectrum
      is, however, red shifted with an increase in intensity with the different doses;
      in the meanwhile, gradual decrease in the visible absorbance has occurred till
      almost complete loss is attained. This bleaching due to ionizing radiation may
      offer an alternative way of data processing in such optical devices based on bR.
      Nevertheless, bR has proofed to be used as a biological indicator of ionizing
      radiation. However, the potential of bR for use as a biosensor to detect ionizing
      radiation should be considered.

PMID- 14968784
TI  - The key to success in space.

PMID- 14968785
TI  - Space, security in the forefront.

PMID- 14968786
TI  - Conversations with Patricia Grace Smith. Interview by Frank Sietzen Jr.

PMID- 14968787
TI  - Levitation yields purer glass.

PMID- 14968788
TI  - Fire the CEO?

PMID- 14968789
TI  - Tobacco money well used, not abused.
AB  - States have spent billion of dollars on health-related services. Even so, they
      are being criticized for using some of the tobacco money to fill budget gaps.

PMID- 14968790
TI  - Nurses identify barriers to educating patients about meds.

PMID- 14968791
TI  - Ethnic disparities lower in states with high penetration of health centers.

PMID- 14968792
TI  - Study confirms strong link between patient and employee satisfaction.

PMID- 14968793
TI  - Biological products; bacterial vaccines and toxoids; implementation of efficacy
      review. Final rule and final order.
AB  - The Food and Drug Administration (FDA) is amending the biologics regulations in
      response to the report and recommendations of the Panel on Review of Bacterial
      Vaccines and Toxoids with Standards of Potency (the Panel). The Panel reviewed
      the safety, efficacy, and labeling of bacterial vaccines and toxoids that have
      standards of potency, bacterial antitoxins, and immune globulins. On the basis of
      the Panel's findings and recommendations, FDA is classifying these products as
      Category I (safe, effective, and not misbranded), Category II (unsafe,
      ineffective, or misbranded), or Category IIIB (off the market pending completion
      of studies permitting a determination of effectiveness).

PMID- 14968794
TI  - Lecture: patents, product exclusivity, and information dissemination: how law
      directs biopharmaceutical research and development.

PMID- 14968795
TI  - Medicaid program; time limitation on record keeping requirements under the drug
      rebate program. Interim final rule with comment period.
AB  - On August 29, 2003, we published a final rule with comment period in the Federal
      Register that finalized two specific provisions: it established new 3-year
      recordkeeping requirements for drug manufacturers under the Medicaid drug rebate
      program and set a 3-year time limitation during which manufacturers must report
      changes to average manufacturer price and best price for purposes of reporting
      data to us. In addition, it announced the pressing need for codification of
      fundamental recordkeeping requirements. On September 26, 2003, we issued a
      correction notice to change the effective date of the August 29, 2003 rule from
      October 1, 2003 to January 1, 2004. In this interim final rule with comment
      period, we are removing the 3-year recordkeeping requirements, replacing them
      with 10-year recordkeeping requirements on a temporary basis, and soliciting
      comments on the 10-year requirements. Manufacturers must retain records beyond
      the 10-year period if the records are the subject of an audit or a government
      investigation of which the manufacturer is aware. These provisions contain a
      sunset date with respect to the record retention requirements to ensure that we
      reexamine whether the retention rule remain necessary and effective. This interim
      final rule with comment period also responds to public comments on the August 29,
      2003 final rule with comment period that pertain to the 3-year recordkeeping
      requirement at Sec. 447.534(h).

PMID- 14968796
TI  - Medicare program; hospital outpatient prospective payment system; payment reform
      for calendar year 2004. Interim final rule with comment period.
AB  - This interim final rule with comment period implements provisions of the Medicare
      Prescription Drug, Improvement, and Modernization Act (DIMA) of 2003 that affect
      the Medicare outpatient prospective payment system (OPPS) that become effective
      January 1, 2004. Sections 303 and 621 of the DIMA include provisions that alter
      the methods for drug payment in hospital outpatient departments, some of which
      become effective January 1, 2004. These provisions affect the methodology for
      paying for pass-through and non-pass-through drugs under the OPPS. Further, the
      new law includes a requirement that all brachytherapy sources be paid separately.
      Section 411 of the DIMA reinstates the hold-harmless protection for small rural
      hospitals with fewer than 100 beds and extends that protection to sole community
      hospitals in rural areas.

PMID- 14968797
TI  - Medicare program; changes to Medicare payment for drugs and physician fee
      schedule payments for calendar year 2004. Interim final rule with comment period.
AB  - This interim final rule implements the provisions of the Medicare Prescription
      Drug, Improvement, and Modernization Act (MPDIMA) of 2003, Pub. L. 108-173, which
      are applicable in 2004 to Medicare payment for covered drugs and physician fee
      schedule services. These provisions revise the current payment methodology for
      Part B covered drugs and biologicals that are not paid on a cost or prospective
      payment basis; make changes to Medicare payment for furnishing or administering
      drugs and biologicals; revise the geographic practice cost indices and change the
      physician fee schedule conversion factor. The 2004 physician fee schedule
      conversion factor will be $37.3374. The 2004 national anesthesia conversion
      factor (prior to making adjustment for the geographic practice cost indices) will
      be $17.4969. The information contained in this final rule related to payment
      under the physician fee schedule supercedes the information contained in the
      November 7, 2003, final rule to the extent that the two are inconsistent. All
      other provisions of the November 7, 2003, final rule are unchanged unless
      otherwise noted. This rule also extends the "opt-out" provisions of 1802(b)(5)(3)
      of the Social Security Act to dentists, podiatrists, and optometrists.

PMID- 14968798
TI  - Providers issue brief: health facilities: year end report-2003.

PMID- 14968799
TI  - [Etiological mechanism and airway remodeling in chronic obstructive lung
      disease].

PMID- 14968800
TI  - HIPAA administrative simplification: standard unique health identifier for health
      care providers. Final rule.
AB  - This final rule establishes the standard for a unique health identifier for
      health care providers for use in the health care system and announces the
      adoption of the National Provider Identifier (NPI) as that standard. It also
      establishes the implementation specifications for obtaining and using the
      standard unique health identifier for health care providers. The implementation
      specifications set the requirements that must be met by "covered entities":
      Health plans, health care clearinghouses, and those health care providers who
      transmit any health information in electronic form in connection with a
      transaction for which the Secretary has adopted a standard (known as "covered
      health care providers"). Covered entities must use the identifier in connection
      with standard transactions. The use of the NPI will improve the Medicare and
      Medicaid programs, and other Federal health programs and private health programs,
      and the effectiveness and efficiency of the health care industry in general, by
      simplifying the administration of the health care system and enabling the
      efficient electronic transmission of certain health information. This final rule
      implements some of the requirements of the Administrative Simplification subtitle
      F of the Health Insurance Portability and Accountability Act of 1996 (HIPAA).

PMID- 14968801
TI  - Human cells, tissues, and cellular and tissue-based products; establishment
      registration and listing. Interim final rule; opportunity for public comment.
AB  - The Food and Drug Administration (FDA) is issuing an interim final rule to except
      human dura mater and human heart valve allografts, currently subject to
      application or notification requirements under the Federal Food, Drug, and
      Cosmetic Act (the act), from the scope of the definition of "human cells,
      tissues, or cellular or tissue-based products (HCT/P's)" subject to the
      registration and listing requirements contained in 21 CFR part 1271. That
      definition became effective on January 21, 2004. FDA is taking this action to
      assure that these products, which are currently subject to the act and therefore
      regulated under the current good manufacturing practice regulations set out in
      the quality system regulations in 21 CFR part 820 are not released from the scope
      of those regulations before a more comprehensive regulatory framework applicable
      to HCT/P's, including donor suitability requirements, good tissue practice
      regulations, and appropriate enforcement provisions, is fully in place. When that
      comprehensive framework is in place, FDA intends that human dura mater and human
      heart valves will be subject to it. FDA intends to revoke this interim final rule
      at that time.

PMID- 14968802
TI  - International Conference on Harmonisation; guidance on Addendum to E2C Clinical
      Safety Data Management: Periodic Safety Update Reports for Marketed Drugs;
      availability. Notice.
AB  - The Food and Drug Administration (FDA) is announcing the availability of a
      guidance entitled "Addendum to E2C Clinical Safety Data Management: Periodic
      Safety Update Reports for Marketed Drugs" (the ICH E2C guidance). The guidance
      was prepared under the auspices of the International Conference on Harmonisation
      of Technical Requirements for Registration of Pharmaceuticals for Human Use
      (ICH). In the Federal Register of May 19, 1997 (62 FR 27470), FDA published the
      ICH E2C guidance, which recommends a unified standard for the format, content,
      and reporting frequency for postmarketing periodic safety update reports (PSURs)
      for drug and biological products. This guidance, an addendum to the ICH E2C
      guidance, provides additional information on the content and format of PSURs,
      including clarification of the objectives, general principles, and model for
      PSURs. This guidance is intended to help harmonize collection and submission of
      postmarketing clinical safety data.

PMID- 14968803
TI  - Final rule declaring dietary supplements containing ephedrine alkaloids
      adulterated because they present an unreasonable risk. Final rule.
AB  - The Food and Drug Administration (FDA, we, our) is issuing a final regulation
      declaring dietary supplements containing ephedrine alkaloids adulterated under
      the Federal Food, Drug, and Cosmetic Act (the act) because they present an
      unreasonable risk of illness or injury under the conditions of use recommended or
      suggested in labeling, or if no conditions of use are suggested or recommended in
      labeling, under ordinary conditions of use. We are taking this action based upon
      the well-known pharmacology of ephedrine alkaloids, the peer-reviewed scientific
      literature on the effects of ephedrine alkaloids, and the adverse events reported
      to have occurred in individuals following consumption of dietary supplements
      containing ephedrine alkaloids.

PMID- 14968805
TI  - Chest X-ray quiz: bronchiectasis.

PMID- 14968806
TI  - Society for neuroscience-33rd annual meeting.

PMID- 14968807
TI  - Society of neuroscience-33rd annual meeting: metabotropic glutamate receptors.

PMID- 14968808
TI  - Society of neuroscience-33rd annual meeting: neurological disorders.

PMID- 14968809
TI  - AACR-NCI-EORTC-15th symposium molecular targets and cancer therapeutics: enzyme
      inhibitors and anti-angiogenics.

PMID- 14968810
TI  - AACR-NCI-EORTC-15th symposium molecular targets and cancer therapeutics: emerging
      targets and pharmacodynamics.

PMID- 14968812
TI  - American society of nephrology-36th annual meeting and renal week 2003.

PMID- 14968813
TI  - Future opportunities & innovative therapies for cardiovascular disease-SMi
      conference.

PMID- 14968814
TI  - Future antivirals-SMi conference: latest developments in HIV, hepatitis, herpes,
      influenza, RSV and SARS.

PMID- 14968815
TI  - Preclinical studies and clinical trials for diabetes-second annual forum:
      identifying emerging therapies and improve trial efficiency.

PMID- 14968816
TI  - European Society of gene therapy-11th annual conference.

PMID- 14968818
TI  - British society for immunology-annual conference 2003.

PMID- 14968835
TI  - Genetic Analysis Workshop II: sib pair screening tests for linkage.
AB  - For each marker locus and for every pair of sibs with data available in the 1983
      workshop data, the proportion of genes identical by descent was estimated. The
      mean proportions were compared between concordant and discordant sib pairs, and
      the mean proportion for concordantly affected pairs was compared with one half.
      Together with standard tests of association, these found to be sensitive
      screening tests for linkage.

PMID- 14968836
TI  - Injuries in hospitals pose threat to patients.

PMID- 14968837
TI  - Asbestos problems in Montana and California.

PMID- 14968838
TI  - Asbestos problems in Montana and California.

PMID- 14968839
TI  - The case against mercury.

PMID- 14968840
TI  - Looking beyond Kyoto.

PMID- 14968841
TI  - Subways grind out a dose of fine metals.

PMID- 14968842
TI  - Deca PBDE flame retardant gets around.

PMID- 14968843
TI  - Streamlining radioactive waste disposal.

PMID- 14968844
TI  - Australasian soil contamination gets attention.

PMID- 14968845
TI  - NOx regulations under way after 24-year delay.

PMID- 14968846
TI  - Creating electricity with undammed hydropower.

PMID- 14968847
TI  - Challenges in ecotoxicology.

PMID- 14968848
TI  - System boundary selection in life-cycle inventories using hybrid approaches.
AB  - Life-cycle assessment (LCA) is a method for evaluating the environmental impacts
      of products holistically, including direct and supply chain impacts. The current
      LCA methodologies and the standards by the International Organization for
      Standardization (ISO) impose practical difficulties for drawing system
      boundaries; decisions on inclusion or exclusion of processes in an analysis (the
      cutoff criteria) are typically not made on a scientific basis. In particular, the
      requirement of deciding which processes could be excluded from the inventory can
      be rather difficult to meet because many excluded processes have often never been
      assessed by the practitioner, and therefore, their negligibility cannot be
      guaranteed. LCA studies utilizing economic input-output analysis have shown that,
      in practice, excluded processes can contribute as much to the product system
      under study as included processes; thus, the subjective determination of the
      system boundary may lead to invalid results. System boundaries in LCA are
      discussed herein with particular attention to outlining hybrid approaches as
      methods for resolving the boundary selection problem in LCA. An input-output
      model can be used to describe at least a part of a product system, and an ISO
      compatible system boundary selection procedure can be designed by applying hybrid
      input-output-assisted approaches. There are several hybrid input-output analysis
      based LCA methods that can be implemented in practice for broadening system
      boundary and also for ISO compliance.

PMID- 14968849
TI  - History and environmental impact of mining activity in Celtic Aeduan territory
      recorded in a peat bog (Morvan, France).
AB  - The present study aims to document historical mining and smelting activities by
      means of geochemical and pollen analyses performed in a peat bog core collected
      around the Bibracte oppidum (Morvan, France), the largest settlement of the great
      Aeduan Celtic tribe (ca. 180 B.C. to 25 A.D.). The anthropogenic Pb profile
      indicates local mining operations starting from the Late Bronze Age, ca. cal.
      1300 B.C. Lead inputs peaked at the height of Aeduan civilization and then
      decreased after the Roman conquest of Gaul, when the site was abandoned. Other
      phases of mining are recognized from the 11th century to modern times. They have
      all led to modifications in plant cover, probably related in part to forest
      clearances necessary to supply energy for mining and smelting. Zn, Sb, Cd, and Cu
      distributions may result from diffusional and biological processes or from the
      influence of groundwater and underlying mineral soil, precluding their
      interpretation for historical reconstruction. The abundance of mineral resources,
      in addition to the strategic location, might explain why early settlers founded
      the city of Bibracte at that particular place. About 20% of the anthropogenic
      lead record was accumulated before our era and about 50% before the 18th century,
      which constitutes a troublesome heritage. Any attempts to develop control
      strategies in accumulating environments should take into account past human
      activities in order to not overestimate the impact of contemporary pollution.

PMID- 14968850
TI  - Direct speciation of phosphorus in alum-amended poultry litter: solid-state 31P
      NMR investigation.
AB  - Amending poultry litter (PL) with aluminum sulfate (alum) has proven to be
      effective in reducing water-soluble phosphorus (P) in the litter and in runoff
      from fields that have received PL applications; it has therefore been suggested
      as a best management practice. Although its effectiveness has been demonstrated
      on a macroscopic scale in the field, little is known about P speciation in either
      alum-amended or unamended litter. This knowledge is important forthe evaluation
      of the long-term stability and bioavailability of P, which is a necessary
      prerequisite forthe assessment of the sustainability of intensive poultry
      operations. Both solid-state MAS and CP-MAS 31P NMR as well as 31P[27Al]-TRAPDOR
      were used to investigate P speciation in alum-amended and unamended PL. The
      results indicate the presence of a complex mixture of organic and inorganic
      orthophosphate phases. A calcium phosphate phase, probably a surface precipitate
      on calcium carbonate, could be identified in both unamended and alum-amended PL,
      as well as physically bound HPO4(2-). Phosphate associated with Al was found in
      the alum-amended PL, most probably a mixture of a poorly ordered wavellite and
      phosphate surface complexes on aluminum hydroxide that had been formed by the
      hydrolysis of alum. However, a complex mixture of organic and inorganic phosphate
      species could not be resolved. Phosphate associated with Al comprised on average
      40 +/- 14% of the total P in alum-amended PL, whereas calcium phosphate phases
      comprised on average 7 +/- 4% in the alum-amended PL and 14 +/- 5% in the
      unamended PL.

PMID- 14968851
TI  - Human-cell mutagens in respirable airborne particles in the northeastern United
      States. 1. Mutagenicity of fractionated samples.
AB  - Few studies have characterized the regional scale (300-500 km) variability of the
      mutagenicity of respirable airborne particles (PM2.5). We previously collected 24
      h PM2.5 samples for 1 year from background, suburban, and urban sites in
      Massachusetts (MA) and rural and urban sites in upstate New York (NY) (n = 53-60
      samples per site). Bimonthly composites of these samples were mutagenic to human
      cells. The present report describes our effort to identify chemical classes
      responsible for the mutagenicity of the samples, to quantify spatial differences
      in mutagenicity, and to compare the mutagenicity of samples composited in
      different ways. Organic extracts and HPLC fractions (two nonpolar, one semipolar,
      and one polar) of annual composites were tested for mutagenicity in the h1A1v2
      cells, a line of human B-lymphoblastoid cells that express cytochrome P450 CYP1A1
      cDNA. The mutagenic potency (induced mutant fraction per microg organic carbon)
      of the semipolarfractions was the highest at all five sites, accounting for 35
      82% of total mutagenic potency of the samples, vs the nonpolar (4-38%) and polar
      (14-32%) fractions. These results are consistent with previous studies. While
      unfractionated extracts exhibited no spatial variations, the mutagenicity of
      semipolar fractions at the NY sites was approximately 2-fold higher than at the
      MA sites. This suggests there may be significant regional differences in the
      sources and/ or transport and transformation of mutagenic compounds in PM2.5. In
      addition, mutagenic potency was sensitive to whether samples were fractionated
      and how they were composited: unfractionated annual composite samples at the NY
      sites were significantly less mutagenic than their semipolar fractions and the
      annual average of bimonthly composites; spatial differences in the mutagenic
      potency of bimonthly composites and the semipolar fractions were not apparent in
      the annual composites.

PMID- 14968852
TI  - Influence of altitude and age in the accumulation of organochlorine compounds in
      fish from high mountain lakes.
AB  - The analysis of hexachlorobenzene, hexachlorocyclohexanes, polychlorobiphenyls,
      and DDTs in muscle of fish from high mountain lakes shows that a proportion of
      their concentration variance depends on fish age and lake altitude.
      Interestingly, the magnitude of this share corresponds linearly with the log
      transformed vapor pressure (Vp) of the organochlorine compounds (OC). Thus, the
      distributions of OC with Vp < 10(-2.5) Pa are mostly determined by these two
      variables. Altitude gradients mainly respond to temperature differences,
      involving concentration increases of 25-150 times between 8.7 and -2.3 degrees C.
      The age effect encompasses concentration increments of 2.4-7.8 for average lake
      differences between 2 and 13 yr. However, both effects are independent since no
      correlation between fish age and lake altitude is observed. Fish liver
      concentrations exhibit the same pattern, but the correlations are only
      significantfor age, suggesting thatthe temperature trend is more related to long
      term accumulation than episodic intake. The temperature effect is independent
      from compound origin. In addition, the sites situated at highest altitude, those
      most distant from possible ground pollution sources, are the most polluted. The
      results can be explained by condensation effects such as those described for the
      latitudinal trends that support the global distillation theory. However, in the
      high altitude lakes a temperature-dependent amplification mechanism, probably
      related to low metabolism and respiration at lowtemperatures, enhances OC
      accumulation in fish beyond the increases predicted from theoretical condensation
      and solubilization enthalpies. The observed temperature dependence suggests that
      a general remobilization of OC accumulated in high mountain areas could take
      place as a consequence of the general warming of these areas anticipated in the
      climatic change studies.

PMID- 14968853
TI  - PBDEs in the atmosphere of three locations in western Europe.
AB  - Atmospheric concentrations of PBDEs (108 samples in total) were measured at 2
      rural/semirural sites in England and 1 remote site on the west coast of Ireland
      in the years 2001 and 2000, respectively. Detailed analysis of the factors
      affecting concentrations is performed. The United Kingdom (UK) has been a major
      producer and user of PBDEs. Concentrations of sigmaPBDEs at Mace Head (MH),
      Ireland ranged between 0.22 and 5.0 pg m(-3) with a mean of 2.6 pg m(-3) and were
      controlled primarily by advection. sigmaPBDEs concentrations at Hazelrigg (HR),
      northwest England, ranged between 2.8 and 37 pg m(-3) with a mean of 12 pg m(-3)
      and at Chilton (CH), southwest England between 3.4 and 33 pg m(-3) with a mean of
      11 pg m(-3). The average mixture of PBDEs in air was similar to that of
      commercial penta-BDE products. Movement of air over local/regional sources
      influenced concentrations of PBDEs at all sites, particularly at MH. At the two
      English sites during the summer, concentrations of PBDEs were strongly influenced
      bytemperature, indicating that air-surface exchange processes play an important
      role. Advection became more influential during winter, particularly at CH, where
      a different congener profile was observed in some samples as ambient air
      temperatures decreased and PBDE concentrations increased. It is hypothesized that
      this was due to increased emissions from diffuse combustion sources.

PMID- 14968854
TI  - Reconstruction of a century of airborne asbestos concentrations.
AB  - Airborne asbestos concentrations have been reconstructed for the entire 20th
      century for the first time through a combination of paleolimnological methods,
      particle-separation techniques, and analytical transmission electron microscopy.
      Pb concentrations and respirable aerosol mass concentrations in air and sediments
      yielded collection efficiencies of approximately 3000 m3 of air per gram of lake
      sediment. Airborne concentrations of chrysotile, the most common type of
      asbestos, reconstructed from control lake sediments echoed chrysotile's usage
      during the 20th century, with the highest concentrations mid-century
      (approximately 0.1 fibers/cm3) and then decreasing in the last quarter century.
      Reconstructed airborne concentrations of anthophyllite asbestos, a byproduct of
      local talc mining and milling, increased from <0.004 to 0.022 fibers/cm3 from
      1846 to 1967. These anthophyllite concentrations during the approximately 100
      year period of talc mining correlated well (r2 = 0.80, p < 0.01) with annual
      production of local talc and were much higher (p = 0.004) than concurrent
      concentrations in a control lake located upwind of the mines and mills. All of
      the chrysotile and more than 70% of the anthophyllite asbestos fibers were too
      narrow to be detected by phase-contrast light microscopy, the method used to
      measure airborne fiber concentrations before approximately 1980.

PMID- 14968855
TI  - Observations on historical, contemporary, and natural PCDD/Fs.
AB  - PCDD/Fs were determined in samples of archived surface soils collected from
      different locations around the world in the early 1880s, in contemporary surface
      soils from around the world, in archived subsurface soils collected at Rothamsted
      Experimental Station in the 1870/1880s, and in sections of peat core deposited
      between 5000 BP and the present. PCDD/Fs were detected in most of the samples.
      The potential sources and implications of the levels and mixtures of PCDD/Fs
      present in the samples are discussed. The homologue and isomer patterns observed
      in most of the contemporary European surface soils are commonly observed for
      European air samples and soil samples. The homologue pattern in the Rothamsted
      surface soils collected in the 1800s was similar, suggesting that similar sources
      of atmospheric emissions of PCDD/ Fs were operating in the UK in the 1800s as
      currently. Very different patterns, dominated by OCDD and with contributions of
      HpCDD and HxCDD, were found in some other samples. It is proposed that the
      PCDD/Fs present in the subsurface Rothamsted soils, archived (1880s) surface
      soils from Illinois and the Congo, clay beneath the peat bog (deposited
      approximately 5000 BP), and possibly surface soil samples from Thailand and
      Australia are of a natural origin. The most abundant TeCDD/F congeners measured
      in the peat samples here were also those observed by previous workers who studied
      a Canadian peat bog and are consistent with the microbially mediated oxidative
      coupling of chlorophenols. The study provides evidence for the widespread
      occurrence of PCDD/Fs in the environment prior to 1900 and for a complex array of
      sources (including natural) and environmental transformation processes.

PMID- 14968856
TI  - Spatial distribution of polybrominated diphenyl ethers in southern Ontario as
      measured in indoor and outdoor window organic films.
AB  - Organic films were collected from indoor and outdoor window surfaces, along an
      urban-rural transect extending northward from Toronto, Ontario, Canada, and
      analyzed for 41 polybrominated diphenyl ether congeners (PBDE). For exterior
      films, urban sigmaPBDE concentrations were approximately 10x greater than rural
      concentrations, indicating an urban-rural gradient and greater PBDE sources in
      urban areas. Urban films ranged from 2.5 to 14.5 ng/m2 (mean = 9.0 ng/ m2),
      excluding the regional "hotspot" Electronics Recycling Facility, compared to 1.1
      and 0.56 ng/m2 at the Suburban and Rural sites. Interior urban films (mean = 34.4
      ng/m2) were 3 times greater than rural films (10.3 ng/m2) and were representative
      of variations in building characteristics. Indoor films were 1.5-20 times greater
      than outdoor films, consistent with indoor sources of PBDEs and enhanced
      degradation in outdoor films. Congener profiles were dominated by BDE-209
      (51.1%), consistent with deca-BDE as the main source mixture, followed by
      congeners from the penta-BDE mixture (BDE-99:13.6% and -47:9.4%) and some octa
      BDE (BDE-183:1.5%). Congener patterns suggest a degradative loss of lower
      brominated compounds in outdoor films versus indoor films. Gas-phase air
      concentrations were back-calculated from film concentrations using the film-air
      partition coefficient (K(FA)). Mean calculated air concentrations were 4.8 pg/m3
      for outdoor and 42.1 pg/m3 for indoor urban sites, indicating that urban indoor
      air is a source of PBDEs to urban outdoor air and the outdoor regional
      environment.

PMID- 14968857
TI  - Elevated airborne exposures of teenagers to manganese, chromium, and iron from
      steel dust and New York City's subway system.
AB  - There is increasing interest in potential health effects of airborne exposures to
      hazardous air pollutants at relatively low levels. This study focuses on sources,
      levels, and exposure pathways of manganese, chromium, and iron among inner-city
      high school students in New York City (NYC) and the contribution of subways.
      Samples of fine particulate matter (PM2.5) were collected during winter and
      summer over 48 h periods in a variety of settings including inside homes,
      outdoors, and personal samples (i.e., sampling packs carried by subjects). PM2.5
      samples were also collected in the NYC subway system. For NYC, personal samples
      had significantly higher concentrations of iron, manganese, and chromium than did
      home indoor and ambient samples. The ratios and strong correlations between pairs
      of elements suggested steel dust as the source of these metals for a large subset
      of the personal samples. Time-activity data suggested NYC subways as a likely
      source of these elevated personal metals. In duplicate PM2.5 samples that
      integrated 8 h of underground subway exposure, iron, manganese, and chromium
      levels (>2 orders of magnitude above ambient levels) and their ratios were
      consistent with the elevated personal exposures. Steel dust in the NYC subway
      system was the dominant source of airborne exposures to iron, manganese, and
      chromium for many young people enrolled in this study, with the same results
      expected for other NYC subway riders who do not have occupational exposures to
      these metals. However, there are currently no known health effects at the
      exposure levels observed in this study.

PMID- 14968858
TI  - PBDEs in European background soils: levels and factors controlling their
      distribution.
AB  - Surface soils (0-5 cm) from remote/rural woodland (coniferous and deciduous) and
      grassland locations on a latitudinal transectthrough the United Kingdom and
      Norway were analyzed for polybrominated diphenyl ethers (PBDEs). Concentrations
      ranged between 65 and 12 000 sigma(ALL)PBDE ng kg(-1) dry weight. PBDE-47, -99, 
      100, -153, and -154-the major constituents of the penta-BDE technical product
      dominated the average congener pattern of the soils. Indeed, the average congener
      composition and distribution measured in these European background soils closely
      matched that reported in the technical penta-BDE product. This is interpreted as
      evidence that transfer of the congeners present in penta-BDE-treated products
      from source-air-soil occurs with broadly similar efficiency, perhaps because
      there has been little weathering/degradation/alteration of the congener source
      pattern by processes operating during atmospheric transport or within the soil
      itself. BDE-183, a marker for the octa-BDE mix, was detected at concentrations
      ranging from <9 to 7000 (median approximately 50 ng kg(-1)). In most soils, it
      made a minor contribution to the sigma(ALL)PBDE concentration, but it was a major
      component in some samples from northern England. Forest soils tended to have
      higher concentrations than grasslands. Underlying the average soil composition,
      some differences in the congener pattern were observed. Notably, there was
      evidence of latitudinal fractionation, with the relative contribution of PBDE-47
      and lighter congeners to the sigmaPBDE increasing northwards (with increasing
      distance from source areas), while the proportion of PBDE-99 and heavier
      congeners decreased. Plots of concentration against percentage soil organic
      matter had different slopes for different congeners. Higher slopes were generally
      seen for the lighter PBDEs (e.g., PBDE-47), indicating that they have undergone
      some air-surface exchange (hopping), while the slopes of heavier congeners (e.g.,
      PBDE-153) were close to zero, indicating that they are retained more effectively
      by soils after deposition.

PMID- 14968859
TI  - Modeling the oxidative capacity of the atmosphere of the south coast air basin of
      California. 1. Ozone formation metrics.
AB  - Metrics associated with ozone (O3) formation are investigated using the
      California Institute of Technology (CIT) three-dimensional air-quality model.
      Variables investigated include the O3 production rate (P(O3)), O3 production
      efficiency (OPE), and total reactivity (the sum of the reactivity of carbon
      monoxide (CO) and all organic gases that react with the hydroxyl radical).
      Calculations are spatially and temporally resolved; surface-level and vertically
      averaged results are shown for September 9, 1993 for three Southern California
      locations: Central Los Angeles, Azusa, and Riverside. Predictions indicate
      increasing surface-level O3 concentrations with distance downwind, in line with
      observations. Surface-level and vertically averaged P(O3) values peak during
      midday and are highest downwind; surface P(O3) values are greater than vertically
      averaged values. Surface OPEs generally are highest downwind and peak during
      midday in downwind locations. In contrast, peaks occur in early morning and late
      afternoon in the vertically averaged case. Vertically averaged OPEs tend to be
      greater than those for the surface. Total reactivities are highest in upwind
      surface locations and peak during rush hours; vertically averaged reactivities
      are smaller and tend to be more uniform temporally and spatially. Total
      reactivity has large contributions from CO, alkanes, alkenes, aldehydes,
      unsubstituted monoaromatics, and secondary organics. Calculations using estimated
      emissions for 2010 result in decreases in P(O3) values and reactivities but
      increases in OPEs.

PMID- 14968860
TI  - Modeling the oxidative capacity of the atmosphere of the south coast air basin of
      California. 2. HOx radical production.
AB  - The production of HOx radicals in the South Coast Air Basin of California is
      investigated during the smog episode of September 9, 1993 using the California
      Institute of Technology (CIT) air-quality model. Sources of HOx(hydroxyl,
      hydroperoxy, and organic peroxy radicals) incorporated into the associated gas
      phase chemical mechanism include the combination of excited-state singlet oxygen
      (formed from ozone (O3) photolysis (hv)) with water, the photolysis of nitrous
      acid, hydrogen peroxide (H2O2), and carbonyl compounds (formaldehyde (HCHO) or
      higher aldehydes and ketones), the consumption of aldehydes and alkenes (ALK) by
      the nitrate radical, and the consumption of alkenes by O3 and the oxygen atom
      (O). At a given time or location for surface cells and vertical averages, each
      route of HOx formation may be the greatest contributor to overall formation
      except HCHO-hv, H2O2-hv, and ALK-O, the latter two of which are insignificant
      pathways in general. The contribution of the ALK-O3 pathway is dependent on the
      stoichiometric yield of OH, but this pathway, at least for the studied smog
      episode, may not be as generally significant as previous research suggests.
      Future emissions scenarios yield lower total HOx production rates and a shift in
      the relative importance of individual pathways.

PMID- 14968861
TI  - Biotransformation of N-ethyl perfluorooctanesulfonamide by rainbow trout
      (Onchorhynchus mykiss) liver microsomes.
AB  - Rainbow trout (Onchorhynchus mykiss) liver microsomes were incubated with N-ethyl
      perfluorooctanesulfonamide [N-EtPFOSA, C8F17SO2NH(C2H5)], to examine the
      possibility of in vitro biotransformation to perfluorooctane sulfonate (PFOS,
      C8F17SO3-) and perfluorooctanoate (PFOA, C7F15COO-). Incubations were performed
      by exposing trout liver microsomes to N-EtPFOSA at 8 degrees C in the dark.
      Reaction mixtures were analyzed after incubation periods of 0, 2, 4, 8, 16, and
      30 h for N-EtPFOSA, PFOS, PFOA, and perfluorooctanesulfonamide (PFOSA,
      C8F17SO2NH2), a suspected intermediate. Amounts of PFOS and PFOSA were found to
      increase with incubation time, but only background levels of PFOA were detected.
      Three possible reaction pathways are proposed for the conversion of N-EtPFOSA to
      PFOS: (i) direct conversion of N-EtPFOSA to PFOS by deethylamination accompanied
      by conversion of the sulfone group to sulfonate, (ii) deethylation of N-EtPFOSA
      to PFOSA, followed by deamination to form PFOS, and (iii) direct hydrolysis of N
      EtPFOSA. These findings represent the first report indicating a possible
      biotransformation of a perfluorosulfonamide to PFOS in fish and may help to
      explain the detection of PFOS, which is relatively involatile, and thus not
      likely to undergo atmospheric transport, in biota from remote regions.

PMID- 14968862
TI  - Adsorption and transport of gas-phase naphthalene on micron-size fog droplets in
      air.
AB  - Aromatic hydrocarbon vapors adsorb to the air/water interface and are transported
      by wet deposition processes via fog, mist, and rain. A falling droplet apparatus
      was used to study the adsorption and uptake of naphthalene vapor on water
      droplets with diameters ranging from 14 to 200 microm. Uptake of naphthalene
      vapor greater than that predicted by bulk (air-water) phase equilibrium was noted
      for diameters less than 50 microm and was attributed to surface adsorption. The
      experimental values of the droplet-vapor partition constants were used to obtain
      the mass accommodation coefficient for naphthalene at the interface. The effect
      of temperature on the mass accommodation coefficientwas measured. The effects of
      a synthetic surfactant and a natural organic carbon surrogate (Suwanee Fulvic
      acid) on the uptake of naphthalene vapors on water droplets were also examined.
      Small droplet diameter, decreased temperature, and the presence of dissolved
      surface-active material in water enhanced the uptake of naphthalene into fog
      droplets.

PMID- 14968863
TI  - Role of Leptothrix discophora in mediating metal uptake in the filter-feeding
      bivalve Mytilus trossulus (edulis).
AB  - The potential for filter-feeding bivalves to accumulate metals from a wide range
      of food sources is an important consideration when examining trophic transfer of
      metals up the food chain. The objective of this study was to determine the role
      of Leptothrix discophora in mediating metal uptake in the filter-feeding bivalve
      Mytilus trossulus. The bacterium L. discophora SP-6 was cultured in the absence
      or presence of Mn, allowing for a naturally formed Mn oxide sheath to develop.
      Secondary metals (Cd and Pb) were then added to the cultures, allowing for
      potential Cd and Pb adsorption to the Mn oxide sheath. Resulting bacterial
      aggregates of known diameter were then fed to the bivalve M. trossulus using a
      flow-through system. Initial concentrations of both Pb and Cd on the bacterium
      did not differ significantly in the presence or absence of the Mn oxide;
      conversely both Pb (F = 7.39, p < 0.0001) and Cd (F= 33.65, p < 0.0001) were
      found at lower concentrations in the mussel tissue when the Mn oxide was present.
      To determine whether these differences in metal uptake could be attributed to
      sorting by the mussel based on food quality, nutritional analysis was performed.
      Bacterial food matrixes containing Mn oxides were found to have significantly
      lower levels of carbon (F = 256, p < 0.0001). Particle clearance rates for the
      various food matrixes were positively correlated with organic content (R2 =
      0.852, p > 0.008). The results of our study suggest that metal uptake in M.
      trossulus was significantly decreased for Cd with a similar trend for Pb when the
      SP-6 sheath contained Mn oxides. The mechanism mediating this differential uptake
      is best explained by food quality, in that a higher quality food source enhanced
      metal uptake due to an increased clearance rate of organic-rich particles by M.
      trossulus.

PMID- 14968864
TI  - Characterization of metal-cyanobacteria sorption reactions: a combined
      macroscopic and infrared spectroscopic investigation.
AB  - In this study, we conducted synchrotron radiation Fourier transform infrared (IR)
      spectroscopy, potentiometric titration, and metal sorption experiments to
      characterize metal-cyanobacteria sorption reactions. Infrared spectra were
      collected with samples in solution for intact cyanobacterial filaments and
      separated exopolymeric sheath material to examine the deprotonation reactions of
      cell surface functional groups. The infrared spectra of intact cells sequentially
      titrated from pH 3.2 to 6.5 display an increase in peak intensity and area at
      1400 cm(-1) corresponding to vibrational COO- frequencies from the formation of
      deprotonated carboxyl surface sites. Similarly, bulk acid-base titration of
      cyanobacterial filaments and sheath material indicates that the concentration of
      proton-active surface sites is higher on the cell wall compared to the overlying
      sheath. A three-site model provides an excellent fit to the titration curves of
      both intact cells and sheath material with corresponding pKa values of 4.7 +/-
      0.4, 6.6 +/- 0.2, 9.2 +/- 0.3 and 4.8 +/- 0.3, 6.5 +/- 0.1, 8.7 +/- 0.2,
      respectively. Finally, Cu2+, Cd2+, and Pb2+ sorption experiments were conducted
      as a function of pH, and a site-specific surface complexation model was used to
      describe the metal sorption data. The modeling indicates that metal ions are
      partitioned between the exopolymer sheath and cell wall and that the carboxyl
      groups on the cyanobacterial cell wall are the dominant sink for metals at near
      neutral pH. These results demonstrate that the cyanobacterial surfaces are
      complex structures which contain distinct surface layers, each with unique
      molecular functional groups and metal binding properties.

PMID- 14968865
TI  - Cl K-edge X-ray spectroscopic investigation of enzymatic formation of
      organochlorines in weathering plant material.
AB  - The contribution of halocarbons from plant weathering to the total organohalogen
      budget of terrestrial systems is gaining recognition. To evaluate the formation
      of such halocarbons, speciation of chlorine in Sequoia sempervirens (redwood)
      needles was examined in the presence of an external chloroperoxidase (CPO) enzyme
      using Cl K-edge X-ray absorption spectroscopy. The Cl forms in fresh and
      naturally weathered needles and in model laboratory reactions were compared. To
      provide a straightforward analogue to the enzymatic chlorination in plants,
      chlorination reactions were conducted for phenol, a common moiety of plant
      macromolecules. Plant material chlorination was also examined in the presence of
      hypochlorite in an ancillary mechanistic investigation. The dominant form of Cl
      in fresh, unreacted plant material was found to be inorganic Cl-, which was
      partially converted to organochlorine in the presence of CPO. Chlorination is
      affected by the nature of reactant (CPO, H2O2) addition, reaction time, and
      temperature. The organochlorines produced in these laboratory investigations
      closely resemble those produced during the natural weathering of redwood needles.
      A striking consistency in chlorine speciation observed among the various sample
      types suggests that (i) CPO produced by terrestrial organisms could play a vital
      role in the generation of organochlorines associated with the degradation of
      plant material and (ii) initial targets of enzymatic chlorination might include
      lignin-like macromolecules rich in aromatic character and hydroxyl groups. These
      findings lend further credibility to a significant biogenic contribution to the
      global organohalogen burden by elucidating a probable route of enzymatic
      chlorination of natural organic matter in terrestrial systems.

PMID- 14968866
TI  - Fate and transport of testosterone in agricultural soils.
AB  - Hormones excreted in animal waste have been measured in surface and groundwater
      associated with manure that is applied to the land surface. Limited studies have
      been done on the fate and transport of androgenic hormones in soils. In this
      study, batch and column experiments were used to identify the fate and transport
      of radiolabeled [14C] testosterone in agricultural soils. The batch results
      indicated that aqueous-phase concentrations decreased for the first 5 h and then
      appeared to increase through time. The first-order sorption kinetics ranged from
      0.08 to 0.640 h(-1) for the first 5 h. Beyond 5 h the increase in aqueous 14C
      could have been caused by desorption of testosterone back into the aqueous phase.
      However, metabolites were also produced beyond 5 h and would have likely resulted
      in the increase in aqueous 14C by sorption site competition and/or by lower
      sorption affinity. There were weak correlations of sorption with soil particle
      size, organic matter, and specific surface area. Testosterone was the dominant
      compound present in the soil column effluents, and a fully kinetic-sorption,
      chemical nonequilibrium model was used to describe the data. Column experiment
      sorption estimates were lower than the batch, which resulted from rate-limiting
      sorption due to the advective transport. The column degradation coefficients
      (0.404-0.600 h(-1)) were generally higher than values reported in the literature
      for 17beta-estradiol. Although it was found that testosterone degraded more
      readily than 17beta-estradiol, it appeared to have a greater potential to migrate
      in the soil because it was not as strongly sorbed. This study underlined the
      importance of the simultaneous transformation and sorption processes in the
      transport of hormones through soils.

PMID- 14968867
TI  - Reactivity of Fe(II)-bearing minerals toward reductive transformation of organic
      contaminants.
AB  - Fe(II) present at surfaces of iron-containing minerals can play a significant
      role in the overall attenuation of reducible contaminants in the subsurface. As
      the chemical environment, i.e., the type and arrangement of ligands, strongly
      affects the redox potential of Fe(II), the presence of various mineral sorbents
      is expected to modulate the reactivity of surficial Fe(II)-species in aqueous
      systems. In a comparative study we evaluated the reactivity of ferrous iron in
      aqueous suspensions of siderite (FeCO3), nontronite (ferruginous smectite SWa-1),
      hematite (alpha-Fe2O3), lepidocrocite (gamma-FeOOH), goethite (alpha-FeOOH),
      magnetite (Fe3O4), sulfate green rust (Fe(II)4Fe(III)2(OH)12SO4 x 4H2O), pyrite
      (FeS2), and mackinawite (FeS) under similar conditions (pH 7.2, 25 m2 mineral/L,
      1 mM Fe(II)aq, O2 (aq) < 0.1 g/L). Surface-area-normalized pseudo first-order
      rate constants are reported for the reduction of hexachloroethane and 4
      chloronitrobenzene representing two classes of environmentally relevant
      transformation reactions of pollutants, i.e., dehalogenation and nitroaryl
      reduction. The reactivities of the different Fe(II) mineral systems varied
      greatly and systematically both within and between the two data sets obtained
      with the two probe compounds. As a general trend, surface-area-normalized
      reaction rates increased in the order Fe(II) + siderite < Fe(II) + iron oxides <
      Fe(II) + iron sulfides. 4-Chloronitrobenzene was transformed by mineral-bound
      Fe(II) much more rapidly than hexachloroethane, except for suspensions of
      hematite, pyrite, and nontronite. The results demonstrate that abiotic reactions
      with surface-bound Fe(II) may affect or even dominate the long-term behavior of
      reducible pollutants in the subsurface, particularly in the presence of Fe(III)
      bearing minerals. As such reactions can be dominated by specific interactions of
      the oxidant with the surface, care must be taken in extrapolating reactivity data
      of surface-bound Fe(II) between different compound classes.

PMID- 14968868
TI  - Uptake and elimination routes of inorganic mercury and methylmercury in Daphnia
      magna.
AB  - Mercury (Hg) is an important environmental pollutant due to its highly toxic
      nature and widespread occurrence in aquatic systems. The biokinetics of Hg in
      zooplankton have been largely ignored in previous studies. This study examines
      the assimilation, dissolved uptake, and efflux of inorganic mercury [Hg(II)] and
      methylmercury (MeHg) in a freshwater cladoceran, Daphnia magna, and models the
      exposure pathways of Hg(II) and MeHg in the daphnids. The assimilation
      efficiencies (AEs) of both Hg species decreased significantly with increasing
      algal carbon concentrations. The dissolved uptake of Hg(II) and MeHg was
      proportional to the ambient concentration (ranging from environmentally realistic
      to high concentration over a 3-4 orders of magnitude variation), whereas MeHg had
      a slightly higher uptake rate constant (0.46 L g(-1) h(-1)) than Hg(II) (0.35 L
      g(-1) h(-1)). Surprisingly, the efflux rate constants of Hg(ll) and MeHg were
      rather comparable (0.041 -0.063 day(-1)). The release of both Hg(II) and MeHg via
      different routes (excretion, egestion, molting, and neonate production) was
      further examined at different food concentrations. It was found that regeneration
      into the dissolved phase was important for D. magna to eliminate both Hg species,
      but maternal transfer of Hg(II) (11-15%) and MeHg (32-41%) to neonates
      represented another important pathway for the elimination of Hg(II) and MeHg from
      the mothers. Modeling results suggest that food is an important source for MeHg
      exposure (47-98%), but water exposure represents 31-96% of Hg(II) accumulation in
      D. magna, depending on the variation of Hg bioconcentration factor in ingested
      food. Furthermore, MeHg predominates the bioaccumulation of Hg in D. magna even
      though MeHg constitutes only a small percentage of the total Hg in the water. The
      results strongly indicate that maternal transfer of Hg(II) and MeHg in freshwater
      zooplankton should be considered in manytoxicity testings and risk assessment in
      aquatic food chains.

PMID- 14968869
TI  - Effects of dissolved carbonate on arsenate adsorption and surface speciation at
      the hematite--water interface.
AB  - Effects of dissolved carbonate on arsenate [As(V)] reactivity and surface
      speciation at the hematite-water interface were studied as a function of pH and
      two different partial pressures of carbon dioxide gas [P(CO2) = 10(-3.5) atm and
      approximately 0; CO2-free argon (Ar)] using adsorption kinetics, pseudo
      equilibrium adsorption/titration experiments, extended X-ray absorption fine
      structure spectroscopic (EXAFS) analyses, and surface complexation modeling.
      Different adsorbed carbonate concentrations, due to the two different atmospheric
      systems, resulted in an enhanced and/or suppressed extent of As(V) adsorption.
      As(V) adsorption kinetics [4 g L(-1), [As(V)]0 = 1.5 mM and I = 0.01 M NaCl]
      showed carbonate-enhanced As(V) uptake in the air-equilibrated systems at pH 4
      and 6 and at pH 8 after 3 h of reaction. Suppressed As(V) adsorption was observed
      in the air-equilibrated system in the early stages of the reaction at pH 8. In
      the pseudo-equilibrium adsorption experiments [1 g L(-1), [As(V)]0 = 0.5 mM and I
      = 0.01 M NaCI], in which each pH value was held constant by a pH-stat apparatus,
      effects of dissolved carbonate on As(V) uptake were almost negligible at
      equilibrium, but titrant (0.1 M HCl) consumption was greater in the air
      equilibrated systems (P(CO2) = 10(-3.5) atm) than in the CO2-free argon system at
      pH 4-7.75. The EXAFS analyses indicated that As(V) tetrahedral molecules were
      coordinated on iron octahedral via bidentate mononuclear ( 2.8 A) and bidentate
      binuclear (approximately equal to 3.3 A) bonding at pH 4.5-8 and loading levels
      of 0.46-3.10 microM m(-2). Using the results of the pseudo-equilibrium adsorption
      data and the XAS analyses, the pH-dependent As(V) adsorption under the P(CO2) =
      10(-3.5) atm and the CO2-free argon system was modeled using surface complexation
      modeling, and the results are consistent with the formation of nonprotonated
      bidentate surface species at the hematite surfaces. The results also suggest that
      the acid titrant consumption was strongly affected by changes to electrical
      double-layer potentials caused by the adsorption of carbonate in the air
      equilibrated system. Overall results suggest that the effects of dissolved
      carbonate on As(V) adsorption were influenced by the reaction conditions [e.g.,
      available surface sites, initial As(V) concentrations, and reaction times].
      Quantifying the effects of adsorbed carbonate may be important in predicting
      As(V) transport processes in groundwater, where iron oxide-coated aquifer
      materials are exposed to seasonally fluctuating partial pressures of CO2(g).

PMID- 14968870
TI  - Formation of PBCDD and PBCDF during flue gas cooling.
AB  - The presence of bromine and chlorine in combustion, particularly in waste
      combustion, results in the formation of PBCDD and PBCDF. Formation pathways of
      PCDD/F are not fully understood, although much is known about them, and they are
      currently being further investigated. PBCDD/F is likely to be formed in reactions
      similar to those leading to PCDD/F, but the processes involved have been less
      intensively studied. In this study a fuel with bromine and chlorine in equal
      molar amounts was combusted in a pilot-scale fluid bed reactor and the cooling
      flue gas was sampled at 800, 350, and 250 degrees C. Analysis revealed that
      levels of PBCDD and PBCDF increased between all sampling ports. The
      chlorine/bromine ratio also increased with reductions in temperature and
      increases in residence time for both PBCDD and PBCDF. However, the formation of
      PBCDD and PBCDF seems to follow different routes with respect to the level and
      pattern of halogenation.

PMID- 14968871
TI  - Photolysis of chloral under atmospheric conditions.
AB  - The photolysis of chloral under atmospheric conditions was studied at the large
      outdoor European Photoreactor (EUPHORE) in Valencia, Spain. The photodissociation
      rate coefficient, J(chloral), was measured directly under different sunlight
      conditions during April 1999. Values in the range of J(chloral) = (4.61-6.11) x
      10(-5) s(-1) were obtained, yielding an average value of J(chloral)/J(NO2) =
      (6.15 +/- 0.62) x 10(-3). This corresponds to a photolysis lifetime of 4.5-6 h
      under conditions appropriate to the solar flux during summer months and confirms
      that atmospheric photolysis is the major degradation pathway for chloral. The
      overall quantum efficiency of photolysis under atmospheric conditions was
      determined to be 1.00 +/- 0.05. The atmospheric photolysis of chloral produced
      phosgene, CO, and Cl atoms with molar yields of 0.83 +/- 0.04, 1.01 +/- 0.05, and
      1.18 +/- 0.06, respectively. The product yield data are consistent with a
      mechanism in which the primary photolysis channel produces a Cl atom and a
      CCl2CHO radical. The latter species is converted to the oxy radical
      OCCl2CHO,which decomposes by both C-C and C-Cl bond fission. A chemical mechanism
      for the photolysis of chloral by sunlight is proposed, and the atmospheric
      implications are discussed.

PMID- 14968872
TI  - Screening analysis of human pharmaceutical compounds in U.S. surface waters.
AB  - The PhATE (Pharmaceutical Assessment and Transport Evaluation) model presented in
      this paper was developed as a tool to estimate concentrations of active
      pharmaceutical ingredients (APIs) in U.S. surface waters that result from patient
      use (or consumption) of medicines. PhATE uses a mass balance approach to model
      predicted environmental concentrations (PECs) in 11 watersheds selected to be
      representative of most hydrologic regions of the United States. The model divides
      rivers into discrete segments. It estimates the mass of API that enters a segment
      from upstream or from publicly owned treatment works (POTW) and is subsequently
      lost from the segment via in-stream loss mechanisms or flow diversions (i.e., man
      made withdrawals). POTW discharge loads are estimated based on the population
      served, the API use per capita, the potential loss of the compound associated
      with human use (e.g., metabolism), and the portion of the API mass removed in the
      POTW. Simulations using three surrogate compounds showthat PECs generated by
      PhATE are generally within an order of magnitude of measured concentrations and
      that the cumulative probability distribution of PECs for all watersheds included
      in PhATE is consistent with the nationwide distribution of measured
      concentrations of the surrogate compounds. Model simulations for 11 APIs yielded
      four categories of results. (1) PECs fit measured data for two compounds. (2)
      PECs are below analytical method detection limits and thus are consistent with
      measured data for three compounds. (3) PECs are higher than (i.e., not consistent
      with) measured data for three compounds. However, this may be the consequence of
      as yet unidentified depletion mechanisms. (4) PECs are several orders of
      magnitude below some measured data but consistentwith most measured data forthree
      compounds. For the fourth category, closer examination of sampling locations
      suggests that the field-measured concentrations for these compounds do not
      accurately reflect human use. Overall, these results demonstrate that PhATE may
      be used to predict screening-level concentrations of APIs and related compounds
      in the environment as well as to evaluate the suitability of existing fate
      information for an API.

PMID- 14968874
TI  - Method development for the determination of diacetyl and acetoin at a microwave
      popcorn plant.
AB  - Separate sampling and analytical methods for the determination of diacetyl and
      acetoin have been developed to assess workplace exposures at a popcorn processing
      facility have been described. Diacetyl (NMAM 2557) is efficiently recovered from
      an Anasorb CMS sampler tube when the composition of methanol in the desorption
      solvent is 1%, and acetoin (NMAM 2558) is efficiently recovered when the
      concentration of methanol is increased to 5%. Desorption efficiencies for
      diacetyl and acetoin were acceptable, 89.9% (RSD = 0.018) and 94.9% (RSD =
      0.019), respectively. Recoveries for nonanone, methyl ethyl ketone, and ethyl
      acetate were not optimized because they were present in very low concentrations
      in the popcorn processing facility and not considered to be major occupational
      health hazards. Samples were collected on Anasorb CMS solid sorbent tubes. All
      analytes were separated using a 30-m Stabilwax-DA fused silica capillary column,
      followed by analysis using gas chromatography with flame ionization detection.
      These methods were acceptable for monitoring and identifying exposures to
      diacetyl and acetoin present in the butter flavoring mixture used at popcorn
      processing facilities. For example, in the initial site visit the method was used
      to determine that maximum workers exposures to diacetyl (462.6 mg/m3), acetoin
      (59.1 mg/m3), and nonanone (0.45 mg/m3) occurred as the butter flavoring was
      added to the mixing kettle. When protective measures were recommended by NIOSH
      personnel and implemented bythe popcorn processing facility, the methods were
      then used to determine the effectiveness of these changes, which showed that
      diacetyl and acetoin concentrations had been reduced significantly to 0.97 and
      2.3 mg/m3, respectively, while the concentration of nonanone fell to levels below
      the detection limit (LOD).

PMID- 14968873
TI  - Global analysis of the riverine transport of 90Sr and 37Cs.
AB  - Atmospheric nuclear weapons explosions and large-scale nuclear accidents may
      contaminate large areas of land with the long-lived radionuclides 137Cs and 90Sr.
      The mobility and bioavailability of these radionuclides in the environment is
      dependent primarily on soil characteristics and changes significantly over time
      after fallout (1-4). Radioisotope concentrations in different rivers and at
      different times after fallout vary over 2-3 orders of magnitude. Many previous
      studies have concentrated on the interactions of radiocesium and radiostrontium
      with various environmental components, but there are currently no operative
      models fortheirtransport over large spatial areas. We collected time-series
      measurements of 90Sr and 137Cs in 25 major European and Asian rivers and (using
      digital data sets with global coverage) determined characteristics of each of the
      rivers' catchments. This work has established, for the first time, a quantitative
      link between riverine transport of these radioisotopes and catchment and soil
      characteristics at a global scale. A generalized predictive model accounting for
      time changes in river concentrations and variation in catchment characteristics
      is developed. This can be used to predict the long-term riverine transport of
      these radiologically important radionuclides following any large-scale nuclear
      incident in North America, Europe, or (European and Asian) Russia.

PMID- 14968875
TI  - Determination of airborne carbonyls: comparison of a thermal desorption/GC method
      with the standard DNPH/HPLC method.
AB  - The standard method for the determination of gaseous carbonyls is to collect
      carbonyls onto 2,4-dinitrophenyl hydrazine (DNPH) coated solid sorbent followed
      by solvent extraction of the solid sorbent and analysis of the derivatives using
      high-pressure liquid chromatography (HPLC). This paper describes a newly
      developed approach that involves collection of the carbonyls onto
      pentafluorophenyl hydrazine (PFPH) coated solid sorbents followed by thermal
      desorption and gas chromatographic (GC) analysis of the PFPH derivatives with
      mass spectrometric (MS) detection. Sampling tubes loaded with 510 nmol of PFPH on
      Tenax sorbent effectively collect gaseous carbonyls, including formaldehyde,
      acetaldehyde, propanal, butanal, heptanal, octanal, acrolein, 2-furfural,
      benzaldehyde, p-tolualdehyde, glyoxal, and methylglyoxal, at a flow rate of at
      least up to 100 mL/min. All of the tested carbonyls are shown to have method
      detection limits (MDLs) of subnanomoles per sampling tube, corresponding to air
      concentrations of <0.3 ppbv for a sampled volume of 24 L. These limits are 2-12
      times lower than those that can be obtained using the DNPH/HPLC method. The
      improvement of MDLs is especially pronounced for carbonyls larger than
      formaldehyde and acetaldehyde. The PFPH/GC method also offers better peak
      separation and more sensitive and specific detection through the use of MS
      detection. Comparison studies on ambient samples and kitchen exhaust samples have
      demonstrated that the two methods do not yield systematic differences in
      concentrations of the carbonyls that are above their respective MDLs in both
      methods, including formaldehyde, acetaldehyde, acrolein, and butanal. The lower
      MDLs afforded by the PFPH/ GC method also enable the determination of a few more
      carbonyls in both applications.

PMID- 14968876
TI  - Natural leathers from natural materials: progressing toward a new arena in
      leather processing.
AB  - Globally, the leather industry is currently undergoing radical transformation due
      to pollution and discharge legislations. Thus, the leather industry is
      pressurized to look for cleaner options for processing the raw hides and skins.
      Conventional methods of pre-tanning, tanning and post-tanning processes are known
      to contribute more than 98% of the total pollution load from the leather
      processing. The conventional method of the tanning process involves the "do-undo"
      principle. Furthermore, the conventional methods employed in leather processing
      subject the skin/ hide to a wide variation in pH (2.8-13.0). This results in the
      emission of huge amounts of pollution loads such as BOD, COD, TDS, TS, sulfates,
      chlorides and chromium. In the approach illustrated here, the hair and flesh
      removal as well as fiber opening have been achieved using biocatalysts at pH 8.0,
      pickle-free natural tanning employing vegetable tannins, and post-tanning using
      environmentally friendly chemicals. Hence, this process involves dehairing, fiber
      opening, and pickle-free natural tanning followed by ecofriendly post-tanning. It
      has been found that the extent of hair removal and opening up of fiber bundles is
      comparable to that of conventionally processed leathers. This has been
      substantiated through scanning electron microscopic analysis and softness
      measurements. Performance of the leathers is shown to be on par with
      conventionally chrome-tanned leathers through physical and hand evaluation. The
      process also exhibits zero metal (chromium) discharge and significant reduction
      in BOD, COD, TDS, and TS loads by 83, 69, 96, and 96%, respectively. Furthermore,
      the developed process seems to be economically viable.

PMID- 14968877
TI  - Direct investigation of the fate of NAPL contaminations in a hydrating cement
      matrix by means of magnetic resonance techniques.
AB  - The behavior of nonwatery solvent phases in hydrating cement pastes is of great
      interest in the context of solidification of wastes containing such phases. In a
      recent study, the influence of various solvents on the hydration kinetics of
      cement was studied. In this paper, we present results on the changes in the
      behavior of the solvent phases themselves during setting of the cement pastes.
      The methods used in the studies were NMR relaxometry and pulsed field gradient
      (PFG) NMR diffusometry. To study selectively the behavior of the non-aqueous
      phase liquid (NAPL) phases, heavy water was used in the preparation of the cement
      pastes. The experimental results are in good agreement with the observations from
      earlier studies concerning the behavior of toluene in hydrating cement. For
      aliphatic solvents (cyclooctane, n-hexanol), indications for surprisingly large
      networks of connected droplets in the cement matrices are found.

PMID- 14968878
TI  - Arsenic(V) removal with polymer inclusion membranes from sulfuric acid media
      using DBBP as carrier.
AB  - Polymer inclusion membranes (PIMs) based on cellulose triacetate (CTA) and
      dibutyl butyl phosphonate (DBBP) were tested for arsenic(V) separation from H2SO4
      for its recovery from copper electrolytes. Solvent extraction experiments allowed
      the determination of the As(V)-DBBP and H2SO4-DBBP complexes formed in the
      organic phase. Application of a transient model to membrane transport experiments
      in solutions containing only arsenic or H2SO4 indicated that it occurred under a
      kinetically controlled regime by formation of H3AsO4[DBBP]2 and H2SO4[DBBP]
      species, respectively. When arsenic and H2SO4 are simultaneously present, the
      existence of a third species, H3AsO4[DBBP][H2SO4], explains well the fact that
      As(V) flux decreases and that H2SO4 flux increases. In both cases, a limiting 50%
      recovery value was obtained. However, active arsenic transport (>50%) is achieved
      if the H2SO4 concentration gradient is assured (e.g., using a triple-cell
      configuration). In this way, high arsenic recovery factors (90% in 800 min) were
      obtained with initial concentrations of 5000 mg/L As(V) and 220 g/L H2SO4. In all
      membrane systems tested, good As(V) selectivity over copper (up to 30000 mg/L)
      was attained.

PMID- 14968879
TI  - Dissolved phosphorus retention of light-weight expanded shale and masonry sand
      used in subsurface flow treatment wetlands.
AB  - Using surface flow constructed wetlands for long-term phosphorus (P) retention
      presents a challenge due to the fact that P is stored primarily in the sediments.
      Subsurface flow wetlands have the potential to greatly increase P retention;
      however, the substrate needs to have both high hydraulic conductivity and high P
      sorption capacity. The objective of our study was to assess the P retention
      capacity of two substrates, masonry sand and lightweight expanded shale. We used
      sorption/desorption isotherms, flow-through column experiments, and pilot-scale
      wetlands to quantify P retained from treated municipal wastewater. Langmuir
      sorption isotherms predicted that the expanded shale has a maximum sorption
      capacity of 971 mg/kg and the masonry sand 58.8 mg/kg. In column desorption and
      column flow-through experiments, the masonry sand desorbed P when exposed to
      dilute P solutions. The expanded shale, however, had very little desorption and
      phosphorus did not break through the columns during our experiment. In pilot
      cells, masonry sand retained (mean +/- standard deviation) 45 +/- 62 g P/m2/yr
      and expanded shale retained 164 +/- 110 g P/m2/yr. We conclude that only the
      expanded shale would be a suitable substrate for retaining P in a subsurface flow
      wetland.

PMID- 14968880
TI  - Retention of arsenic and selenium compounds using limestone in a coal
      gasification flue gas.
AB  - Volatile arsenic and selenium compounds present in coals may cause environmental
      problems during coal combustion and gasification. A possible way to avoid such
      problems may be the use of solid sorbents capable of retaining these elements
      from flue gases in gas cleaning systems. Lime and limestone are materials that
      are extensively employed for the capture of sulfur during coal processing.
      Moreover, they have also proven to have good retention characteristics for
      arsenic and selenium during combustion. The aim of this work was to ascertain
      whether this sorbent is also useful for retaining arsenic and selenium species in
      gases produced in coal gasification. The study was carried out in a laboratory
      scale reactor in which the sorbent was employed as a fixed bed, using synthetic
      gas mixtures. In these conditions, retention capacities for arsenic may reach 17
      mg g(-1) in a gasification atmosphere free of H2S, whereas the presence of H2S
      implies a significant decrease in arsenic retention. In the case of selenium, H2S
      does not influence retention which may reach 65 mg g(-1). Post-retention sorbent
      characterization, thermal stability, and water solubility tests have shown that
      chemical reaction is one of the mechanisms responsible for the capture of arsenic
      and selenium, with Ca(AsO2)2 and CaSe being the main compounds formed.

PMID- 14968881
TI  - Solution chemistry effects on orthophosphate adsorption by cationized solid wood
      residues.
AB  - Adsorption of orthophosphate anions in aqueous solution by cationized milled
      solid wood residues was characterized as a function of sorbate-to-sorbent ratio
      (approximately equal to 0.001-2.58 mmol of P/g substrate), pH (3-9), ionic
      strength, I (no I control; 0.001 and 0.01 M NaCl), reaction time (4 min to 24 h),
      and in the presence of other competing anions (0.08-50 mM SO4(2-); 0.08-250 mM
      NO3-). Sorption isotherms revealed the presence of two kinds of adsorption sites
      corresponding to high and low binding affinities for orthophosphate anions.
      Consequently, a two-site Langmuir equation was needed to adequately describe the
      data over a range of solution conditions. In addition to higher sorption
      capacity, cationized bark possessed a higher binding energy for orthophosphate
      anions compared to cationized wood. The sorption capacity and binding energy for
      bark were 0.47 mmol of P g(-1) and 295.7 L mmol(-1), respectively, and for wood,
      the corresponding values were 0.27 mmol g(-1) and 61.4 L mmol(-1). Both the
      sorption capacity and binding energy decreased with increasing I, due to
      competition from Cl- ions for the available anion-exchange sites. The surface
      charge characteristics of cationized bark (pHzpc = 7.9) acted in concert with
      orthophosphate speciation to create a pH-dependent sorption behavior.
      Orthophosphate uptake was quite rapid and attained equilibrium levels after 3 h.
      Both SO4(2-) and NO3- influenced percent removal but required high relative
      competing anion to H2PO4- molar ratios, i.e., 2.5-3 for SO4(2-) and 25 for NO3-,
      to cause appreciable reduction. These results support our hypothesis that
      adsorption of orthophosphate anions on cationized bark involves ion exchange and
      other specific Lewis acid-base interactions.

PMID- 14968882
TI  - Phosphate adsorption on aluminum-impregnated mesoporous silicates: surface
      structure and behavior of adsorbents.
AB  - Phosphorus from excess fertilizers and detergents ends up washing into lakes,
      creeks, and rivers. This overabundance of phosphorus causes excessive aquatic
      plant and algae growth and depletes the dissolved oxygen supply in the water. In
      this study, aluminum-impregnated mesoporous adsorbents were tested for their
      ability to remove phosphate from water. The surface structure of the materials
      was investigated with X-ray diffraction (XRD), a N2 adsorption-desorption
      technique, Fourier transform-infrared (FT-IR), and X-ray photoelectron
      spectroscopy (XPS) to understand the effect of surface properties on the
      adsorption behavior of phosphate. The mesoporous materials were loaded with Al
      components by reaction with surface silanol groups. In the adsorption test, the
      Al-impregnated mesoporous materials showed fast adsorption kinetics as well as
      high adsorption capacities, compared with activated alumina. The uniform
      mesopores of the Al-impregnated mesoporous materials caused the diffusion rate in
      the adsorption process to increase, which in turn caused the fast adsorption
      kinetics. High phosphate adsorption capacities of the Al-impregnated mesoporous
      materials were attributed to not only the increase of surface hydroxyl density on
      Al oxide due to well-dispersed impregnation of Al components but also the
      decrease in stoichiometry of surface hydroxyl ions to phosphate by the formation
      of monodentate surface complexes.

PMID- 14968883
TI  - Hydrogen sulfide oxidation by a microbial consortium in a recirculation reactor
      system: sulfur formation under oxygen limitation and removal of phenols.
AB  - Wastewater from petroleum refining may contain a number of undesirable
      contaminants including sulfides, phenolic compounds, and ammonia. The
      concentrations of these compounds must be reduced to acceptable levels before
      discharge. Sulfur formation and the effect of selected phenolic compounds on the
      sulfide oxidation were studied in autotrophic aerobic cultures. A recirculation
      reactor system was implemented to improve the elemental sulfur recovery. The
      relation between oxygen and sulfide was determined calculating the O2/S2- loading
      rates (Q(O2)/Q(S)2- = Rmt), which adequately defined the operation conditions to
      control the sulfide oxidation. Sulfur-producing steady states were achieved at
      Rmt ranging from 0.5 to 1.5. The maximum sulfur formation occurred at Rmt of 0.5
      where 85% of the total sulfur added to the reactor as sulfide was transformed to
      elemental sulfur and 90% of it was recovered from the bottom of the reactor.
      Sulfide was completely oxidized to sulfate (Rmt of 2) in a stirred tank reactor,
      even when a mixture of phenolic compounds was present in the medium. Microcosm
      experiments showed that carbon dioxide production increased in the presence of
      the phenols, suggesting that these compounds were oxidized and that they may have
      been used as carbon and energy source by heterotrophic microorganisms present in
      the consortium.

PMID- 14968884
TI  - Arsenic removal using mesoporous alumina prepared via a templating method.
AB  - The health threat of arsenic is well-known, and the U.S. EPA recommends the
      maximum contaminant level to be 0.01 ppm or less for arsenic in drinking water.
      Therefore, advanced treatment processes are needed for finished water to meet the
      required regulations. Adsorption is considered to be a less expensive procedure
      that is safer to handle than precipitation, ion exchange, and membrane
      filtration. Activated alumina (AA) is the most commonly used adsorbent for the
      removal of arsenic from aqueous solutions. However, conventional porous solids
      including AA have ill-defined pore structures and, typically, low adsorption
      capacities and act in a kinetically slow manner. An ideal adsorbent should have
      uniformly accessible pores, an interlinked pore system, a high surface area, and
      physical and/or chemical stability. To meet this requirement, mesoprous alumina
      (MA) with a wide surface area (307 m2/g) and uniform pore size (3.5 nm) was
      prepared, and a spongelike interlinked pore system was developed through a post
      hydrolysis method. The resulting MA was insoluble and stable within the range of
      pH 3-7. The maximum uptake of As(V) by MA was found to be 7 times higher [121 mg
      of As(V)/g and 47 mg of As(III)/ g] than that of conventional AA, and the
      kinetics of adsorption were also rapid with complete adsorption in less than 5 h
      as compared to the conventional AA (about 2 d to reach half of the equilibrium
      value). A desorption study using sodium hydroxide solutions (0.01-1 M) was
      conducted, and 0.05 M NaOH was found to be the most suitable desorption agent.
      More than 85% of the arsenic adsorbed to the MA was desorbed in less than 1 h.
      Several other activated aluminas with different pore properties were also tested.
      The results show that the surface area of the adsorbents does not greatly
      influence on the adsorption capacity. In fact, the key factor is a uniform pore
      size and an interlinked pore system. These studies show that MA with a wide
      surface area, uniform pore size, and interlinked pore system can be used as an
      efficient adsorbent for the removal of arsenic.

PMID- 14968885
TI  - In situ observation of CO2 sequestration reactions using a novel microreaction
      system.
AB  - A novel, externally controlled microreaction system has been developed to provide
      the first in situ observations of the reaction processes that control CO2
      sequestration via mineral carbonation. The system offers pressure (to 20 MPa),
      temperature (to 250 degrees C), and activity control suitable for investigating a
      variety of fluid-fluid and fluid-solid interactions of environmental interest.
      Mineral sequestration efforts to date have effectively accelerated carbonation, a
      natural mineral weathering process, to an industrial timescale. However, the
      associated reaction mechanisms are poorly understood, limiting further process
      development. Synchrotron X-ray diffraction and Raman spectroscopy have been used
      to provide the first in situ insight into the associated supercritical mineral
      carbonation process. Magnesite was found to form directly under the reaction
      conditions observed (e.g., 150 degrees C and 15 MPa CO2),facilitating
      geologically stable sequestration. Thermodynamic analysis of fluid-phase species
      concentrations in the Na+ buffered H2O-CO2 reaction system found the primary
      aqueous reactant species to be CO2(aq) and HCO3-, with CO2(aq) more prevalent
      under the reaction conditions observed. The microreactor provides a powerful new
      tool for in situ investigation of a broad range of environmentally,
      fundamentally, and commercially important processes, including the reactions
      associated with geological carbon dioxide sequestration.

PMID- 14968886
TI  - Extraction of heavy metals from soils using biodegradable chelating agents.
AB  - Metal pollution of soils is widespread across the globe, and the clean up of
      these soils is a difficulttask. One possible remediation technique is ex-situ
      soil washing using chelating agents. Ethylenediaminetetraacetic acid (EDTA) is a
      very effective chelating agent for this purpose but has the disadvantage that it
      is quite persistent in the environment due to its low biodegradability. The aim
      of our work was to investigate the biodegradable chelating agents [S,S]
      ethylenediaminedisuccinic acid (EDDS), iminodisuccinic acid (IDSA), methylglycine
      diacetic acid (MGDA), and nitrilotriacetic acid (NTA) as potential alternatives
      and compare them with EDTA for effectiveness. Kinetic experiments showed for all
      metals and soils that 24 h was the optimum extraction time. Longer times only
      gave minor additional benefits for heavy metal extraction but an unwanted
      increase in iron mobilization. For Cu at pH 7, the order of the extraction
      efficiency for equimolar ratios of chelating agent to metal was EDDS > NTA> IDSA
      > MGDA > EDTA and for Zn it was NTA > EDDS > EDTA >MGDA > IDSA. The comparatively
      low efficiency of EDTA resulted from competition between the heavy metals and co
      extracted Ca. For Pb the order of extraction was EDTA > NTA >EDDS due to the much
      stronger complexation of Pb by EDTA compared to EDDS. At higher concentration of
      complexing agent, less difference between the agents was found and less pH
      dependence. There was an increase in heavy metal extraction with decreasing pH,
      but this was offset by an increase in Ca and Fe extraction. In sequential
      extractions EDDS extracted metals almost exclusively from the exchangeable,
      mobile, and Mn-oxide fractions. We conclude that the extraction with EDDS at pH 7
      showed the best compromise between extraction efficiency for Cu, Zn, and Pb and
      loss of Ca and Fe from the soil.

PMID- 14968887
TI  - Issues in diagnosis of attention-deficit/hyperactivity disorder in adolescents.

PMID- 14968888
TI  - Practice guidelines for the management of febrile infants less than 90 days of
      age at the ambulatory network of a large pediatric health care system in the
      United States: summary of new evidence.

PMID- 14968889
TI  - Autonomic syncope in pediatrics: a practice-oriented approach to classification,
      pathophysiology, diagnosis, and management.
AB  - This paper presents a practice-oriented approach to the problem of syncope in
      pediatrics. Autonomic syncope is the major etiologic category in pediatrics and
      consists of 2 types: reflex and dysautonomic. The latter type is rare in
      pediatrics. Reflex syncope has 4 subtypes: neurocardiogenic, central,
      situational, and cerebral. Neurocardiogenic syncope, the most common subtype, is
      easily diagnosed by taking a careful, detailed history; identifying diagnostic
      red flags; performing a complete physical examination; and ordering a minimum of
      laboratory tests. Patient and parent education is essential, and usually, without
      medication, outcomes are good.

PMID- 14968890
TI  - Lymphadenopathy in children: when and how to evaluate.

PMID- 14968891
TI  - Every nose counts: a new influenza vaccine for all healthy schoolchildren?
AB  - Influenza is a vaccine-preventable disease. However, influenza virus spreads
      among children in schools and daycare centers, then to families and communities,
      causing uncontrolled epidemics every winter. The United States Food and Drug
      Administration evaluated and approved an investigational live-attenuated, cold
      adapted, trivalent influenza vaccine for licensure, for prevention of influenza
      in healthy children and healthy adults, 5 through 49 years of age. Could
      protection of healthy schoolchildren against influenza limit its spread and
      benefit society?

PMID- 14968892
TI  - 22q13 deletion syndrome: an update and review for the primary pediatrician.
AB  - Recent advances in genetic testing can help to provide a specific diagnosis to
      children born with syndromes that result in congenital anomalies and
      developmental delay. One such emerging condition is the 22q13 deletion syndrome.
      With the introduction of subtelomeric fluorescence-in-situ hybridization (FISH)
      analysis, the 22q13 deletion has become recognized as a relatively widespread and
      underdiagnosed cause of mental retardation. Primary-care physicians play an
      important role in the care of children with 22q13 deletion syndrome, from
      suspecting the diagnosis in a developmentally delayed child through the medical,
      developmental, and behavioral aspects of their care. Furthermore, they serve as a
      valuable source of support and advocacy for the family and a resource for other
      care providers. The remainder of this article addresses the current state of
      knowledge regarding 22q13 deletion syndrome and offers the primary-care physician
      a framework in which to provide care and information.

PMID- 14968893
TI  - Are pediatric practice settings adolescent friendly? An exploration of attitudes
      and preferences.
AB  - This study describes adolescent preferences about offices and waiting. Fifty-four
      adolescents participated in 12 discussion groups, which were audiotaped and
      transcribed. The transcripts were analyzed qualitatively. Two themes emerged
      about the health care environment: (1) making the interior design less childish,
      more teen-oriented, and more home-like; and (2) decreasing waiting time and
      enhancing waiting experience by providing teen diversions (e.g., magazines, tv,
      games). Teens preferred that artwork portray realistic images, that medical
      paraphernalia be hidden, and that colors be neutral. Modifying interior decor,
      constructing smaller subwaiting areas, and incorporating diversions that are teen
      oriented may help promote positive health care experiences and utilization by
      adolescents.

PMID- 14968894
TI  - Readmission for newborn jaundice: the value of the Coombs' test in predicting the
      need for phototherapy.
AB  - Current practice at our hospital is to perform a direct antiglobulin test (DAT)
      on cord blood samples of all infants born to blood type O or Rh-negative mothers.
      Measurement of serum total bilirubin (STB) level and follow-up after discharge
      are at the discretion of the individual physician. The purposes of the present
      study were, first, to determine the clinical utility of performing a routine DAT
      and, second, to define the clinical characteristics of infants readmitted to the
      hospital for phototherapy. The study was done over a 1-year period extending from
      January 1 to December 31, 2000. A retrospective review of the DAT results of all
      infants born to type O or Rh-negative mothers was conducted. The 2 groups of
      infants included those who had a positive cord blood DAT and were treated with
      phototherapy and those who needed readmission to the hospital for phototherapy.
      We found that routine DAT testing of cord blood from term nonjaundiced infants
      born to O positive mothers is not necessary. Infants with 2 or more risk factors
      for jaundice irrespective of the results of the DAT are at an increased risk for
      needing readmission for phototherapy.

PMID- 14968895
TI  - Accuracy and precision of low-dose insulin administration using syringes, pen
      injectors, and a pump.
AB  - We compared the accuracy and precision of low-dose insulin administration using
      various devices including, for the first time, an insulin pump. We dispensed 1,
      2, and 5 unit(s) of soluble insulin (100 units/mL) 15 times each from a NovoPen
      (3.0 mL), a BD-Mini Pen (1.5 mL), a Humalog Pen (100 units/mL), 30G Precision
      Sure-Dose Insulin Syringes, 30G BD Ultra-Fine II Short Needle Syringes, and a H
      TRON-plus V100 insulin pump. Each dose was weighed on an analytical scale, and
      the delivered and target doses were compared. Accuracy was defined by the
      absolute percent difference from the target dose. Precision was defined as the
      absolute percent difference from the group sample mean. Overall, we found that
      the pen and pump devices were more accurate, and the pump more precise, than the
      syringes at the 1- and 2-unit doses. Syringes were dangerously inaccurate,
      clinically, at the 1-unit dose. The use of pens and syringes with very fine
      increment markings (1/2 unit) did not improve accuracy or precision. Earlier
      researchers used multiple individuals to draw and weigh the samples. In an effort
      to eliminate the potential introduction of significant error; our study used only
      2 investigators: 1 to draw up the doses and another to weigh them. The
      conclusions in our study were similar to prior studies.

PMID- 14968896
TI  - Management of febrile children in the conjugate pneumococcal vaccine era.
AB  - The objective of this study was to evaluate physician attitudes toward the
      management of young febrile children since the introduction of the conjugate
      heptavalent pneumococcal vaccine (PCV 7). Seven thousand five hundred
      pediatricians and 7,500 emergency department (ED) physicians were surveyed with
      regard to their management of a febrile 7-month-old child and 20-month-old child
      without an apparent fever focus. Specifically, physicians were asked how they
      would manage a febrile child who had and who had not been vaccinated with PCV 7.
      When evaluating a febrile 7-month-old child, pediatricians would order 5% fewer
      complete blood cell (CBC) counts and 6% fewer blood cultures (p<0.0001) if a
      child was vaccinated. ED physicians would order 13% fewer CBC's and 15% fewer
      blood cultures (p<0.0001). ED physicians and pediatricians ordered fewer chest
      radiographs, an 8% and 3% decrease, respectively (p<0.0001). For the PCV 7
      immunized 20-month-old child, pediatricians ordered 6% fewer CBC counts and 8%
      fewer blood cultures (p<0.0001). ED physicians would perform 12% fewer CBC counts
      and cultures (p<0.0001). Four percent fewer pediatricians and 10% fewer ED
      physicians would order chest radiographs (p<0.0001). When treating the vaccinated
      7-month-old child, pediatricians would use 11% less ceftriaxone and ED physicians
      20% less (p<0.0001). Twelve percent fewer pediatricians and 19% fewer ED
      physicians would administer ceftriaxone (p<0.0001) for the 20-month-old
      vaccinated child. Our survey suggests that pediatricians and ED physicians would
      order fewer CBC counts and blood cultures and administer less empiric ceftriaxone
      if a child was vaccinated with PCV 7.

PMID- 14968897
TI  - Accuracy of parental reporting of immunization.
AB  - This study was undertaken to evaluate the reliability of parental reporting of
      their children's immunization status. One hundred eight consecutively admitted
      children to Brookdale University Hospital and Medical Center were sampled during
      October and November 2001. Review of the immunization record, recording the
      immunizations documented, and matching it with the parents' report was done for
      children in whom the parents brought the cards. The primary care physician was
      contacted to verify the immunization status for children for whom the parents did
      not bring the card during hospitalization or for whom there was a mismatch
      between the card and the parents' report. The study included 100 patients (8 were
      excluded). Forty-nine patients had their immunization cards on admission; 18
      brought the cards later during the hospital stay. Of the 100 parents questioned,
      98 stated that their children are up to date and 2 stated that their children are
      missing vaccinations. Of the 98 parents who stated that their children are up to
      date, 2 were found not to be up to date. Ninety-eight percent of parents were
      aware of their children's immunization status and were accurate with their
      reporting. Parents are knowledgable of their children's immunization status (98%
      parental accuracy) and their statements can be relied on during history-taking.
      It is important for each child to have a primary care physician.

PMID- 14968898
TI  - Clinician satisfaction with vaccination visits and the role of multiple
      injections, results from the COVISE Study (Combination Vaccines Impact on
      Satisfaction and Epidemiology).
AB  - Because little is known about clinician satisfaction with infant vaccination
      visits, we measured satistaction and the effects of the number of injections on
      satisfaction. Clinicians from 35 pediatric centers self-administered a
      questionnaire using visual analog scales augmented by a Likert scale. All 95
      pediatricians and 137 nonphysician vaccinators responded. In both populations,
      increased injections predicted decreased overall satisfaction, and decreased
      satisfaction with obtaining consent, time to prepare/administer, getting upset
      during administration, and time to update records (each p<0.01). Satisfaction
      decreased markedly, on each measure, at 4-injection visits, 5-injection visits,
      or both.

PMID- 14968899
TI  - Probiotic prophylaxis in pediatric recurrent urinary tract infections.

PMID- 14968900
TI  - Systemic side effects of ophthalmic drops.
AB  - Topical application of ocular drugs may cause serious adverse ocular or systemic
      side effects. Children are at greater risk for systemic side effects because
      ocular dosing is not weight-adjusted, and infants are especially vulnerable as a
      consequence of the inability to efficiently metabolize the drug, and/or an
      immature blood-brain barrier. Four pediatric patients are reported in whom
      treatment with topical brimonidine, a selective alpha-2 adrenoceptor agonist,
      indicated for the treatment of glaucoma, produced somnolence. Anti-glaucoma
      eyedrops that are not approved for use in children are still used frequently in
      pediatrics. Therefore, physicians should be aware of possible systemic side
      effects of ophthalmic drops.

PMID- 14968901
TI  - A comparison of domestic violence screening methods in a pediatric office.

PMID- 14968902
TI  - Vegan diet and vitamin A deficiency.

PMID- 14968903
TI  - Cocoa powder aspiration.

PMID- 14968904
TI  - A swollen knee and tremor.

PMID- 14968905
TI  - [Focusing on the subsidized health regime in Colombia].
AB  - Based on the results of the project "Evaluation of the Processes of the
      Subsidized health regime" in Colombia, a reflection is presented about the
      beneficiary selection system--Sisben as a tool to affiliate people to the
      subsidized health regime. The multiple interpretations which have been given to
      the Sisben as an instrument to focalize the health services in the poorest
      populations, are documented and analyzed. This has been interpreted, amongst
      others, as a measure of the magnitude of poverty, as an approximate indicator of
      resources or income, or as an evaluation of fulfillment of needs. It was found
      that amongst the 19 million of poor people living in Colombia in 1997, less than
      half of them, 8.9 million, have been included in levels 1 and 2 of Sisben, which
      represents an exclusion error of 53.1%. Of the 10.6 million persons classified in
      these levels, 1.6% are not poor, giving an inclusion error of 14.9%. The
      exclusion errors are much more serious than the inclusion ones, because they mean
      a denial of equal rights and services for all those who are in similar
      conditions, according to the criteria for assignation of subsidies.

PMID- 14968906
TI  - [Use of health services and epidemiological profiles as parameters for adjusting
      the Compulsory Health Plan in Colombia].
AB  - OBJECTIVE: To evaluate the use of health services and the epidemiological
      profiles as parameters for adjusting the contents of the Compulsory Health Plan-
      POS. METHODS: An evaluative study of the contents of the Compulsory Health Plan-
      POS was performed regarding the use of health services and the regional
      epidemiological profiles, within the framework of the current problems of the
      General System of Health Social Security. The 1994 Survey on Equity of the Fiscal
      Expenditure, the 1997 National Survey on Quality of Life, and the 2000 National
      Household Survey estimated the use of services. The epidemiological profiles were
      obtained from the 2000 mortality data of the National Administrative Statistics
      Department--DANE. RESULTS: Affiliation to the health system has only reached 56%
      of the total population. However, health expenditure has increased constantly
      between 1993 and 2000, from 7.2% to nearly 10% of the GNP. Greater use of health
      services was found among the elderly population, and people with greater levels
      of spending. Women, particularly those residing in urban areas and on the higher
      quintile of spending, are the people who most use the health services. The people
      who use health services the least are men in urban areas in the lower quintile of
      spending. CONCLUSIONS: Organizing the Compulsory Health Plan with a modular
      structure makes it possible to adjust it according to the parameters of the use
      of health services and epidemiological profiles, in such a way that it
      contributes to the opportunity and pertinence of services, as well as to increase
      the affiliation to the system.

PMID- 14968907
TI  - [Estimate of the incidence of occupational diseases in Colombia, 1985-2000].
AB  - OBJECTIVES: The occurrence of labor related diseases in Colombia is unknown. The
      objective of this study was to estimate the incidence of occupational disease in
      Colombia in the period 1985-2000. METHODS: The annual incidence was estimated
      with the methodology recommended by Leigh et al. based upon the population
      estimates of the National Administrative Statistics Department (DANE). RESULTS:
      The results showed an increase in the incidence of occupational diseases from
      68,063 cases in 1985 to 101,645 in 2000. DISCUSSION: The economic losses caused
      to the social security health system by underreporting of occupational diseases
      are estimated.

PMID- 14968908
TI  - [Evaluation of results and impact of the first phase of a community based mental
      health model in localities in Bogota, D.C].
AB  - OBJECTIVES: The results and impact of the first phase of a Community Based Mental
      Health Model, developed in the South network by the Bogota Health authority and
      the Tunjuelito hospital during 2002 were evaluated. The first phase of the
      program included the formation of health community agents, communitary screening
      of mental health done through home visits, referrals to the services network and
      an increase in the nodes of the network of good treatment. METHODS: The
      indicators of before (year 2001) and after (year 2002) the application of the
      model were compared, as well as the variations between the study groups (South
      network) and the control group (Central-Eastern network). RESULTS: The mental
      health model increased the notification of cases of family violence (23.8% in the
      study group vs. 15.3% in the control group), the followup of cases of family
      violence (80% vs. 25%) and the conectivity of the networks of good treatment. In
      the localities in which the mental health component of the Basic Attention Plan
      is strengthened, the mental health model showed a better performance.
      CONCLUSIONS: The results suggest that the implementation of a community based
      mental health model favors the notification of cases of family violence, their
      followup and a greater community composition in the social networks of good
      treatment.

PMID- 14968909
TI  - [A model of health promotion with emphasis on physical activity for university
      students].
AB  - OBJECTIVE: The project was designed towards a model of health promotion based
      upon physical activity and directed to the students of the National University of
      Colombia. METHODS: A three phase multilevel analysis method was employed. Both
      the disease and the population problems presented by the students were examined
      and documented, and the information on both of these problems was integrated. In
      second place, the previous experiences were identified and finally the axes and
      strategies of the model were established. RESULTS: A model was defined whose main
      components are the networks of participation and support to the promotion of
      health and physical activity, the political and regulatory support and
      transformation, and the academic reorientation towards an integral formation and
      its strategies. CONCLUSIONS: The project reassured a methodology for designing
      health models, as well as it favored the integration, from a practical
      perspective, of the strategies and approaches of health promotion applied to
      physical activity.

PMID- 14968910
TI  - Evaluation of insulin sensitivity in clinical practice and in research settings.
AB  - Insulin resistance is the core metabolic abnormality in type 2 diabetes. Its high
      prevalence and its association with dyslipidemia, hypertension, hyperinsulinemia,
      and high coronary and cerebrovascular mortality put it in the forefront as the
      plausible target for aggressive intervention. Measurements of insulin sensitivity
      provide clinicians and clinical researchers with invaluable instruments to
      objectively evaluate the efficiency of both current and potentially useful
      interventional tools. Although several methods had been developed and validated
      to evaluate insulin sensitivity, none of these methods can be universally used in
      all patients. Nonetheless, a method suitable for use in clinical or basic
      research may not necessarily be a practical method for use in clinical practice
      or for epidemiologic research. We reviewed the currently used methods for
      assessment of insulin sensitivity. For each method, we summarized its procedure,
      normal value, cut-off value for defining insulin resistance, advantages and
      limitations, validity, accuracy for each patient population, and suitability for
      use in clinical practice and in research settings. The methods reviewed include
      fasting plasma insulin, homeostatic model assessment, quantitative insulin
      sensitivity check index, glucose-to-insulin ratio, continuous infusion of glucose
      with model assessment, indices based on oral glucose tolerance test, insulin
      tolerance test, and the so called "gold standard" methods, the hyperinsulinemic
      euglycemic clamp and the frequently sampled-intravenous glucose tolerance test.

PMID- 14968911
TI  - The assessment of cognitive performance in children: considerations for detecting
      nutritional influences.
AB  - The accurate assessment of cognitive performance in children is critical for
      detecting the effects of micronutrient deficiency or supplementation on the
      developing brain and its functions. Relatively little attention has been paid to
      the selection of culturally appropriate measures that are sensitive enough to
      detect the subtle cognitive changes that could be expected following nutritional
      intervention. Normal brain development and the emergence of cognitive abilities
      throughout infancy and childhood is discussed in this paper, followed by a
      description of the more pertinent and sensitive neuropsychological tests that can
      be used to assess cognitive performance and investigate the effects of
      micronutrient deficiency and supplementation on cognitive development among
      children in a variety of cultures.

PMID- 14968912
TI  - Ciliary neurotrophic factor: a role in obesity?
AB  - Ciliary neurotrophic factor (CNTF) is a neurocytokine expressed by glial cells in
      peripheral nerves and the central nervous system. CNTF is generally recognized
      for its function in support and survival of non-neuronal and neuronal cell types.
      Following a serendipitous finding, CNTF was recently acknowledged for its
      potential role in the control of obesity.

PMID- 14968913
TI  - New paradigms for nutrient control of genome translation.
AB  - Organisms respond adaptively to changing environmental conditions by altering
      genome expression. Translational control of gene expression by nutrients and
      metabolites is one of the most robust biologic mechanisms that enable rapid
      alterations in the cellular proteome in response to changes in the local
      environment. Recently, investigators have identified new mechanisms for nutrient
      control of translation in mammals; evidence supports the conservation of
      translational control mechanisms in eukaryotes that heretofore had only been
      demonstrated in prokaryotes.

PMID- 14968914
TI  - Lower body mass index cut-off values for obesity in China.

PMID- 14968915
TI  - [Generalized adenopathy as a manifestation of type 2 reactional leprosy].
AB  - Generalized adenopathy as a manifestation of type 2 reactional leprosy Leprosy
      patient's reactions are severe clinical manifestations of acute inflammation of
      chronic lesions, capable of producing irreversible and invalidating damage. We
      studied a 46 year-old man with a type 2 leprosy reaction, who presented fever,
      cutaneous nodules, nasal obstruction and generalized adenopathy. The hemogram
      showed leucocytosis with neutrophilia. None of the initial diagnoses included
      leprosy. A lymph node biopsy revealed extensive necrotic areas infiltrated with
      polymorphonuclear lymphocytes, and foamy macrophages. Eosinophylic necrosis and
      thrombosis of venules with lymphoid nodule depletion was also in evidence. Ziehl
      Neelsen stain was not done, but the Gomori stain clearly showed Hansen's bacilli.
      These were were not detected by the pathologist and therefore a final diagnosis
      was not provided. Twenty months later, the patient presented similar symptoms,
      but with more generalized lymphadenopathy and presence of cutaneous nodules.
      Nodule biopsy showed lepromatous leprosy with erythema nodusum leprosum or type 2
      reaction. Polychemotherapy treatment and anti-reaction treatment with thalidomide
      cured the patient. No sequelae were noted in 3 years following the treatment. A
      literature review of the type 2 reaction in leprosy is provided, including
      discussion of risk factors, histopathology, differential diagnosis for leprosy
      adenopathy, pathogenesis, prognosis, and treatment. Type 2 leprosy must be
      treated immediately upon diagnosis as it can cause serious and permanent tissue
      damage. As had occurred in the above patient, the disease can proceed with
      generalized and symptomatic lymphadenopathy.

PMID- 14968916
TI  - [Egg morphology as an indirect method to identify Anopheles benarrochi, Anopheles
      oswaldoi and Anopheles rangeli (Diptera: Culicidae)].
AB  - In the Department of Putumayo in southern Colombia, malaria transmission has
      continued in the absence of the 4 traditional Latin American vector species-
      Anopheles darlingi, Anopheles nuneztovari, Anopheles albimanus or Anopheles
      trinkae. Human bait collections yielded Anopheles mosquitoes and a morphological
      variant of Anopheles benarrochi, the adult females of which can easily be
      misidentified as Anopheles oswaldoi. Species identification of females of
      Anopheles in the subgenus Nyssorhynchus is generally difficult due to overlapping
      morphological characters; therefore, progeny of field collected females were link
      reared to assess species identity. Herein a robust method is presented to
      identify the species Anopheles benarrochi, Anopheles oswaldoi and Anopheles
      rangeli from southern Colombia, using the morphology of the eggs induced from
      wild-caught females. Eggs of A. rangeli and A. benarrochi were differentiated on
      the basis of the anterior crown. In A. rangeli, this feature is positioned
      apically with high walls. In A. benarrochi, anterior crown is positioned more
      ventrally with comparatively shorter walls. No crown is present in A. oswaldoi.
      These differences are clear with the aid of a dissecting microscope and make
      accurate species determination possible even in field conditions. Egg morphology
      is shown to be an accurate, albeit indirect, method for the taxonomic
      determination for the three southern Colombian species and may also be useful in
      other regions of Latin America where the morphological variant of A. benarrochi
      is sympatric with A. oswaldoi.

PMID- 14968917
TI  - Feeding success of Lutzomyia evansi (Diptera: Psychodidae) experimentally exposed
      to small mammal hosts in an endemic focus of Leishmania chagasi in northern
      Colombia.
AB  - Lutzomyia evansi is the vector of Leishmania chagasi in northern Colombia.
      Differences in feeding success were revealed, when this phlebotomine sand fly was
      fed on five species of small mammal hosts from an endemic focus of visceral
      leishmaniasis. In each trial, 50 female sand flies were provided access to
      similar-sized depilated areas of the hind foot of each of 44 individual mammals
      and allowed to feed for 30 minutes. The number of engorged sand flies was counted
      at the end of each trial and compared among host species by analysis of variance
      and Tukey's multiple comparisons test. Sand flies fed least successfully on
      Sciurus granatensis, a common squirrel in the endemic area. It has not been found
      infected with L. chagasi. Intermediate numbers of sand flies engorged on
      Heteromys anomalus and Zygodontomys brevicauda, but these two mammals have not
      been found infected with L. chagasi and are not expected to be important in
      transmission. Sand flies fed most successfully on Didelphis marsupialis and
      Proechimys canicollis. These are the two most abundant mammals in the endemic
      area and frequently are infected. Results provided further evidence that these
      two species are the wild mammals with the greatest impact on transmission of L.
      chagasi in northern Colombia.

PMID- 14968918
TI  - [Evaluation of medication side-effects from an economic perspective].
AB  - Pharmacovigilance is a health sciences discipline devoted to the data collection,
      data analysis and decision-making related to adverse drug reactions (ADR). It has
      played an expanded theoretical and practical role since the 1960's. However, few
      studies have made a careful analysis of the decision-making costs in evaluating
      ADRs. Herein, the relevant literature is reviewed concerning the costs generated
      due to the attention of the drug adverse events in medical practice. Examples are
      taken from international literature which offer by extrapolation of the potential
      future costs of ADR in Colombia. The objective is to sensitize and generate
      insights about the need for implementation and development of a national
      pharmacovigilance system.

PMID- 14968919
TI  - Expression of transforming growth factor-beta and platelet-derived growth factor
      in linear scleroderma.
AB  - Linear scleroderma (LS) is a localized form of scleroderma characterized by
      mononuclear cell infiltration and fibroblast proliferation. In the later stages
      of the disease, excessive collagen is deposited with concomitant skin and
      appendage atrophy. These symptoms suggest a breakdown of fibroblast cell
      function, and consequently, growth factors have been thought to play a role in
      the pathogenesis of LS. The present study examined the expression of TGF-beta and
      PDGF in skin biopsies obtained from patients with LS and from normal subjects.
      Samples were prepared for immunohistochemistry. To identify TGF-beta, two
      polyclonal antibodies were used: TGF-beta1 (RaB4) and TGF-beta2 (CL-B1/29) and,
      to identify PDGF, two monoclonal antibodies were used: PDGF-AA (3E-205) and PDGF
      BB (1F-133). Staining for TGF-beta1 and TGF-beta2 was observed around blood
      vessels (endothelial cells), and sweat glands in both LS and normal skin.
      Staining for PDGF-AA and PDGF-BB was intense in endothelial cells and sweat
      glands in LS and normal skin. Mononuclear cell infiltrates and abnormal collagen
      bundles did not stain for TGF-beta or PDGF. The strength and extent of staining
      was evaluated in tissues using a scale from zero (no staining) to four (strong
      staining). The amount of TGF-beta1, TGF-beta2, PDGF-AA and PDGF-BB was found
      similar in LS and normal skin. These results do not support the hypothesis that
      the excessive fibroblast cell activity and abnormal collagen deposition observed
      in LS are associated with downregulation of TGF-beta or PDGF.

PMID- 14968920
TI  - [Prenatal and postnatal effects of dengue infection during pregnancy].
AB  - The risk of dengue virus infection during pregnancy has increased due to the
      current rash of frequent and severe dengue epidemics. The effects of dengue virus
      in the fetus and newborn children have been studied only superficially and with
      contradictory results. Therefore, a retrospective cohort study was conducted in
      Medellin, Colombia, to describe the fetal and postnatal effects of dengue virus
      infection acquired during pregnancy. Twenty-two babies born from mothers who
      suffered dengue during the epidemics of 1998 were compared with babies from non
      infected mothers. In the exposed cohort, three premature births occurred, three
      children suffered from fetal anomalies and four children were born with low
      weight. In the non-exposed children, none of these problems were found.
      Psychomotor development was normal in both groups. Only the low weight subgroup
      was statistically significant (Fisher test, p = 0.045). These results suggested
      that the children from women with dengue during pregnancy present low weight,
      greater frequency of premature birth and increased fetal distress. A larger
      sample is necessary to confirm these results.

PMID- 14968921
TI  - Molecular cloning and characterization of two hsp 70 homologous genes from the
      dimorphic fungus Paracoccidioides brasiliensis.
AB  - Paracoccidioides brasiliensis, a dimorphic fungus, is the etiologic agent of
      Paracoccidioidomycosis (PCM), one of the most important systemic mycosis in Latin
      America. Two genes (2.2 and 1DB5) were cloned, characterized and sequenced; they
      showed homology with members of hsp70 gene family. By using several probe
      fragments derived from these genes, levels of expression for each gene were
      determined by Northern blot during transition to the yeast phase. The highest
      level of hsp70 transcript occurred between 30 min to 6 hours after temperature
      shift, with significant reduction after 36-48 hours. However, after 72 hours, the
      level of the transcription increased until yeast phase was reached. As a response
      to temperature increase, hsp 70 genes are expressed during the transition phase
      and possibly play a role in the differentiation process.

PMID- 14968922
TI  - [Levels of plasma cholinesterase in Colombian working-class populations].
AB  - Levels of plasma cholinesterase in Colombian working-class populations Reference
      values for plasma cholinesterase (EC 3.1.1.8) are not available for Colombian
      populations. A representative sample of a working-class population was used to
      establish these values to provide reference data for use by the social security
      system. Two working-class populations were sampled from the Aburra Valley
      (Aburra) and eastern Antioquia (Oriente). Cholinesterase activity was measured in
      827 workers, with ages spanning 18-49 years, 415 from Aburra and 412 people from
      Oriente. Three methods were used to measure cholinesterase: Michel, EQM and
      Monotest The average values by Michel and EQM were not statistically different
      between regions (Michel: Aburra, 1.11, and East, 1.13 deltas pH/hora; EQM:
      Aburra, 2.55, and Oriente, 2.48 U/ml). By the Monotest, the enzyme average was
      statistically higher in Aburra than in Oriente (5,743 and 5,459 U/L respectively;
      p = 0 .012). By region and technique, men had significantly higher enzymatic
      levels than women. Within both regions and sexes, no statistically significant
      difference among the three aged groups was noted. Our obtained Colombian values
      differed significantly from foreign reference values: Michel and Monotest levels
      were higher and EQM levels were lower. For making clinical and epidemiologic
      decisions in Colombia related to these data, the values obtained for the
      Colombian populations are preferred over values derived from external sources.

PMID- 14968923
TI  - [Effectiveness of the antibiotics chloramphenicol and rifampin in the treatment
      of Streptococcus pneumoniae-induced meningitis and systemic infections].
AB  - Streptococcus pneumoniae, a common pathogen in pediatric infections, has become
      resistant to penicillin and make these infections difficult to treat. Rifampin
      and chloramphenicol have been recommended as alternative therapies, since they
      are less costly and more accessible to communities with limited resources.
      However, their use may be restricted by the differing levels of resistance found
      in target populations. The objective was to determine minimal inhibitory
      concentration (MIC) and minimal bactericidal concentration (MBC) for
      chloramphenicol and rifampin in strains of S. pneumoniae. These strains were
      newly isolated from children under age 5 that had demonstrated systemic
      infections and meningitis. A subgroup of 107 isolates of S. pneumoniae was
      selected from 324 strains isolated during a period of 2 years (1994-1996). Among
      these isolates, 60 were penicillin-resistant and 47 were susceptible; 53 isolates
      were from children with meningitis. MIC and MBC for chloramphenicol and
      rifampicin were obtained by standard methods recommended by the National
      Committee for Clinical Laboratory Standards (NCCLS). S. pneumoniae ATCC strain
      49619 served as the control. An isolate was considered susceptible to
      chloramphenicol when MIC = 4 microg/ml and resistant when MIC = 8 microg/ml. A
      strain was considered susceptible to rifampin when MIC = 1 microg/ml and
      resistant when MIC = 4 microg/ml. MBC was determined by recording the lower
      concentration of the antibiotic that inhibited 99.9% of the initial inoculum.
      Chloramphenicol resistance was found in 21% of the 107 isolates. In the group
      susceptible to penicillin, 11% were resistant to chloramphenicol and in the group
      resistant to penicillin 28% was resistant to chloramphenicol as well. MBC was
      found > 4 microg/ml in 28% of the isolates susceptible to penicillin and in 60%
      of the resistant isolates. No isolates were found resistant to rifampin. However,
      2 penicillin resistant isolates showed CBM > 1 microg/ml to rifampin, and one
      with CIM = 1 microg/ml had a MBC to rifampicin of 16 microg/ml. Meningitis
      isolates showed higher CIM and CBM than the group of total isolates. These data
      suggest that chloramphenicol is not recommended for invasive infections caused by
      S. pneumoniae in Colombia. Rifampin is a more effective therapy in combination
      with other antibiotics for treatment of this kind of infections. Further studies
      are necessary to clarify the significance of low levels of MBC to rifampin found
      in some strains, since this may affect the efficacy of therapies that include
      this antibiotic.

PMID- 14968924
TI  - [Neurological effects of American trypanosomyiasis: clinical aspects].
AB  - Trypanosoma cruzi, causative agent of Chagas disease, affects not only cardiac
      and intestinal structures but also neurological structures. A high prevalence of
      T. cruzi infection occurs in Colombia, prompting the present study. First, a
      qualitative metaanalysis was undertaken using the PubMed database, the electronic
      internet engine Altavista, Colombian journals indexed by Colciencias, and three
      relevant textbooks. The following key words were used: Trypanosoma, Chagas
      disease, nervous system, spinal cord, central nervous system, peripheral nervous
      system, neuromuscular junction, autonomic nervous system, muscle, muscle
      disorders, neuromuscular disease, neuromuscular disorders, synapticopathies and
      dysautonomia. The documents analyzed numbered 116 and included original papers,
      reviews, case reports, editorials, brief communications, conferences and book
      chapters. At minimum, each document included data involving ELISA testing,
      indirect immunofluorescense, or parasitemia levels in the clinical, serological
      or histopathological studies. Polymerase chain reaction (PCR) studies were not
      included because of the recent introduction of PCR as a confirmatory technique
      for Chagas disease in Colombia. Chagas disease affects the central, the
      peripheral and the autonomic nervous system in humans, although its effects on
      the antonomic system is most commonly investigated in Colombia. Neurological
      lesions must be evaluated carefully, because patients may be misdiagnosed and
      treated as carriers of 'idiopathic' diseases. Neurological pathologies poses a
      serious threat in Colombia due to the prevalence of Chagas disease.

PMID- 14968925
TI  - [Isolation and characterization of macrophages-foam cells from aorta of
      hypercholesterolemic rabbit].
AB  - Evidence has accumulatd to support the hypothesis that atherosclerosis involves
      lipid imbalance as well as inflammatory responses mediated by macrophage and foam
      cells. These findings have been based on animal models. To rationalize animal use
      and to propose an alternative biological model, a technique was standardized for
      macrophage-foam cell isolation and culture. The cultures were characterized by
      non-denaturing polyacrylamide gel electrophoresis (PAGE) of nonspecific esterases
      and histochemical staining. This method has not been applied previously for the
      characterization of the non specific esterases from leucocytes. The biological
      model presented here can be used to study macrophage-foam cell responses related
      to atherosclerosis.

PMID- 14968926
TI  - Determination of trace cobalt concentrations in human serum by adsorptive
      stripping voltammetry.
AB  - The goal of our study was to develop an accurate and reliable method for
      determining trace cobalt concentrations in human serum. The method was used to
      determine cobalt in the sera of healthy persons and patients with orthopaedic
      implants containing cobalt - a possible source of systemic release of cobalt into
      the human body. This goal is of vital interest since cobalt and its compounds are
      classified by IARC as potentially carcinogenic to humans. We used an
      electrochemical method, adsorptive stripping voltammetry (AdSV), which made
      possible the low detection limit and high sensitivity needed for measurements in
      human serum. The serum was acid digested by a combination of H2SO4, HNO3 and H2O2
      in a 10 mL Kjeldhal flask. The digested sample was then dissolved in 0.1 mol/L
      ammonia buffer, pH 9.0 +/- 0.2. The determination is based on the adsorptive
      collection of the complex of cobalt (II) with dimethylglyoxime on a hanging
      mercury drop electrode (HMDE). The optimum values of adsorption potential and
      time were determined to be -0.8 V and 60 s. The optimisation of the sample
      digestion protocol and measurement procedures ensured the reliable assessment of
      low cobalt concentrations, down to 0.03 microg/L. The mean concentration of serum
      cobalt in four healthy persons was 0.11 +/- 0.06 microg/L, and in four patients
      with total hip replacements 0.34 +/- 0.07 microg/L. This method will be used
      routinely for measuring serum cobalt levels in patients with total hip
      replacements.

PMID- 14968927
TI  - Iron bioavailability and weight gains to iron-deficient rats fed a commonly
      consumed Tunisian meal 'bean seeds ragout' with or without beef and with green or
      black tea decoction.
AB  - The Fe bioavailability and the weight gains were evaluated in rats fed a commonly
      consumed Tunisian meal 'bean seeds ragout' (BSR), with or without beef and with
      black or green tea decoction. The Fe bioavailability was evaluated in Fe
      deficient rats by the hemoglobin repletion method and the Fe stored in the liver.
      The addition of beef to the BSR significantly increased the Fe bioavailability
      from this meal by 147% and the reserve of Fe stored in the liver by 77% (P <
      0.001). In contrast, both black and green tea decoctions caused a significant
      decrease of the Fe bioavailability from BSR meal (-19.6 +/- 4.9% and -14.9 +/-
      4.1%, respectively). The reserve of Fe stored in the liver was significantly
      lower in the BSR, the black and the green tea groups than in the positive control
      group (FeSO4). The weight gains were significantly lower in the black and the
      green tea groups (3.9 +/- 5.7 g, 13 +/- 1.9 g, respectively) than in the BSR
      group (24.9 +/- 6 g). The addition of beef to BSR meal counteracted the
      inhibitory effect of the kidney bean and considerably improved the Fe
      bioavailability and the Fe stored in the liver of rats. The green tea decoction,
      which constitutes an important source of antioxidant factors, had the same
      inhibitory effect as the black tea decoction on the Fe bioavailability from BSR
      meal. In addition, both black and green teas significantly reduced the weight
      gains, where the black tea decoction has the most effect.

PMID- 14968928
TI  - Mercury and selenium in whole blood and serum in relation to fish consumption and
      amalgam fillings in adolescents.
AB  - Mercury and selenium in whole blood and serum of 245 17-year old Swedish
      adolescents were analysed. The relationships between these elements'
      concentrations and the consumption of fish as well as the number of dental
      amalgam fillings were studied. The geometric means (GM) of the mercury
      concentrations were 1.1 microg/L in blood and 0.43 microg/L in serum. The mean
      selenium concentration in blood was 110 microg/L and the GM of the serum selenium
      concentration 110 microg/L. Fish species with dietary restrictions due to
      elevated mercury Levels (i.e. pike, perch, pikeperch, burbot, eel and halibut)
      were consumed on average 0.7 times/month and fish species without such
      restrictions 4.1 times/month. Despite this comparatively low fish consumption,
      the adolescents' blood mercury concentrations were positively correlated with
      fish consumption. Of the adolescents, 39% had amalgam fillings (mean 2 +/- 1.5).
      Serum mercury was influenced by the number of amalgam fillings, by fish
      consumption, blood and serum levels of selenium and the residential area. Blood
      and serum selenium concentrations were not influenced by fish consumption, but
      were positively associated with the serum mercury concentration.

PMID- 14968929
TI  - Plasma iron is associated with lipid peroxidation in an elderly population.
AB  - Epidemiological evidence has raised concern that a moderate elevation in body
      iron stores may increase oxidative stress and risk of heart disease. We examined
      the cross-sectional association between plasma iron and factors that could affect
      its levels (antioxidant enzymes, diet), with the concentration of plasma
      malondialdehyde (MDA) as a marker of lipid peroxidation. Participants were 162
      non-smoking institutionalised elderly. Our results show that those in the highest
      tertile of plasma iron were at least twice as likely to have higher plasma MDA
      levels. Among the factors affecting plasma iron levels, we found that the upper
      tertile of erythrocyte-superoxide dismutase (E-SOD) was inversely associated with
      higher plasma iron, and potato intake explained a sizeable proportion of the
      variation in plasma iron levels. In addition to potatoes, eggs, wine, fruit in
      men and green vegetables in women showed a positive association with plasma iron
      levels. Only potatoes in both sexes, wine in men and eggs in women had an
      independent effect on plasma MDA. Potatoes, wine, plasma lycopene and plasma iron
      accounted for 43% of the variability in plasma MDA for males, and E-SOD,
      potatoes, eggs, plasma lycopene and plasma iron explained 45% for women. A
      longitudinal study should confirm, whether these MDA levels are related to
      morbidity and mortality.

PMID- 14968930
TI  - Liver copper content of rats hypo- or hyperresponsive to dietary cholesterol.
AB  - The question addressed is whether cholesterol intake reduces the hepatic copper
      content in rats. For this purpose we have compared the hepatic copper content of
      two selected rat inbred strains after feeding the animals a control or a high
      fat, high cholesterol diet. One strain was dietary cholesterol resistant
      (SHR/OlaIpcv), whereas the other strain was susceptible to dietary cholesterol
      (BN-Lx/Cub). Dietary cholesterol-susceptible rats have a lower baseline hepatic
      copper content when compared with their resistant counterparts. The consumption
      of a hypercholesterolemic diet decreased the liver copper concentration
      (expressed in microg/g dry weight) to about the same extent in both strains.
      However, dietary cholesterol did not reduce the absolute (expressed as
      microg/whole liver) and relative (expressed as microg/whole liver/100 g body
      weight) copper store of rats. The decrease of liver copper concentration after
      the high fat, high cholesterol diet is probably not caused by a decrease in whole
      hepatic copper content, but rather due to dietary-induced hepatomegaly.

PMID- 14968931
TI  - Effect of increasing selenite concentrations, vitamin E supplementation and
      different fetal calf serum content on GPx1 activity in primary cultured rabbit
      hepatocytes.
AB  - Primary rabbit hepatocytes from 6 week old female New Zealand White rabbits (3.0
      x 10(6) viable hepatocytes per treatment) were incubated for 24 h or 48 h with
      two basic variants of the selenium and vitamin E free DMEM/F12-HAM nutrition
      medium containing 2.5% or 10% fetal calf serum (FCS). Selenium and vitamin E
      concentrations of the media were varied by the addition of 0, 10, 50 and 100 ng
      Se/mL medium as sodium selenite and 100 microg alpha-tocopheryl acetate/mL.
      Lactic dehydrogenase (LDH) leakage of the hepatocytes was not influenced by the
      various selenium concentrations of the media, whereas vitamin E addition
      significantly inhibited LDH release. The activity of cellular glutathione
      peroxidase (GPx1) was markedly induced by increasing the selenium supplementation
      of the culture media. Vitamin E supply further enhanced GPx1 induction. In
      hepatocytes cultivated at the lower serum concentration (2.5% FCS), increasing
      the selenite concentration of the media raised GPx1 and reduced the intracellular
      levels of the reduced tripeptide glutathione (GSH). No vectored relation between
      the selenium concentration of the media and the activity of superoxide dismutase
      (SOD) could be observed. After both incubation periods (24 h and 48 h) SOD
      activity was significantly higher in the cytosol of hepatocytes grown in media
      containing 10% FCS as compared to cells incubated at the 2.5% FCS level.
      Furthermore, SOD activity was reduced by the addition of vitamin E to the media.
      In conclusion the results indicate an effective metabolism of rabbit hepatocytes
      for selenite even in amounts as low as nanograms. A general cytoprotective role
      for vitamin E can be shown by its ability to decrease LDH leakage and by the
      reduction of SOD activity.

PMID- 14968932
TI  - The effect of zinc on endothelium-dependent relaxation of blood-vessels and on
      the ultrastructure of endothelial cells under immobilization stress.
AB  - We investigated the effects of zinc on the function and ultrastructure of
      endothelial cells in the case of a 48-day immobilization stress provoked in
      Chinchilla male rabbits (n=18) by placing them in metal hutches. Half of those
      rabbits (n=9) received an daily oral supplement of zinc at a dose of 0.3 mg/kg
      body weight (in the form of zinc acetate). The control rabbits had no
      intervention and received no supplement of zinc. The relaxation of smooth muscles
      from thoracic aorta as mediated by acetylcholine at concentrations from 10(-8)
      mol/L to 10(-4) mol/L was determined in isometric regime. Responses were
      expressed as the percentage of relaxation to prostaglandin F2alpha (2.10(-5)
      mol/L)-induced precontraction. The ultrastructure of endothelial cells was
      evaluated by electron microscopy. The level of total cholesterol and zinc in the
      blood serum was determined by an enzymatic method and by atomic absorption
      spectrometry, respectively. In rabbits receiving no zinc supplement, the
      relaxation of smooth muscles under the influence of acetylcholine concentrations
      from 10(-8) mol/L to 10(-4) mol/L was significantly (P < 0.05-0.01) lower than in
      rabbits receiving a supplement of zinc and lower than in control rabbits. Also,
      in the rabbits not receiving the zinc supplement, the level of total blood serum
      cholesterol was increased, but the concentration of zinc decreased. In rabbits
      receiving the zinc supplement, the contractility of the smooth muscles effected
      by acetylcholine did not change as compared with control rabbits, and we found a
      normal structure of endothelial cells and a normal level of total cholesterol and
      zinc in their blood serum. Thus, zinc played an important role in the maintenance
      of the normal ultrastructure and function of the endothelial cells in the rabbits
      receiving zinc under immobilization stress.

PMID- 14968933
TI  - Serum calcium, zinc, and copper in relation to biomarkers of lead and cadmium in
      men.
AB  - The influence of exposure to lead and cadmium on serum concentrations of calcium,
      zinc, and copper was examined in 299 healthy Croatian men 20-55 years of age,
      including 143 workers in a lead battery factory and 156 control subjects. The
      interrelationship of blood lead, activity of delta-aminolevulinic acid
      dehydratase, erythrocyte protoporphyrin, blood cadmium, age, smoking habits, and
      alcohol consumption with respect to serum calcium, zinc, and copper levels was
      calculated by forward stepwise multiple regression. The results showed that
      chronic moderate exposure to lead decreased serum zinc, calcium and, to a lesser
      extent, copper levels. Exposure to cadmium occurred mostly through smoking and
      seemed to contribute to a decrease of serum zinc. All changes in serum
      concentrations of these essential elements were significant but remained within
      the normal range. The results suggest possible mechanisms of lead- and/or cadmium
      induced adverse health effects in humans.

PMID- 14968934
TI  - Zinc, copper and iron concentrations in cerebral cortex of male rats exposed to
      formaldehyde inhalation.
AB  - Retrospective cohort studies and clinical findings have suggested effects of
      formaldehyde exposure on the central nervous system in anatomists, embalmers and
      pathologists. On the other hand, harmful effects of formaldehyde inhalation on
      the nervous system are not well documented. The concentrations of elements such
      as zinc, copper and iron within the cerebral cortex indicate whether
      physiological conditions are maintained. In this study, adult male albino Wistar
      rats were exposed to formaldehyde at different concentrations (0; 6.1; 12.2 mg x
      m(-3)) and during different periods of time (subacute-subchronic), and body
      weights were recorded weekly. Zinc, copper and iron concentrations were measured
      in the parietal cortex using atomic absorption spectrometry after wet ashing. We
      conclude that subacute or subchronic exposure to formaldehyde may cause growth
      retardation and alter zinc, copper and iron levels in the cerebral cortex.

PMID- 14968935
TI  - Mechanisms of hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) is the major causative agent of chronic non-A, non-B
      hepatitis. The life cycle of HCV is largely unknown because a reliable culture
      system has not yet been established. HCV presumably binds to specific receptor(s)
      and enters cells through endocytosis, as do other members of Flaviviridae. The
      viral genome is translated into a precursor polyprotein after uncoating, and
      viral RNA is synthesized by a virus-encoded polymerase complex. Progeny viral
      particles are released into the luminal side of the endoplasmic reticulum and
      secreted from the cell after passage through the Golgi apparatus. Understanding
      the mechanisms of HCV infection is essential to the development of effective new
      therapies for chronic HCV infection. Several host membrane proteins have been
      identified as receptor candidates for HCV. Recent advances using pseudotype virus
      systems have provided information surrounding the initial steps of HCV infection.
      An HCV RNA replicon system has been useful for elucidating the replication
      mechanism of HCV. In this review, we summarize our current understanding of the
      mechanisms of HCV infection and discuss potential antiviral strategies against
      HCV infection.

PMID- 14968936
TI  - Development of new antivirals for herpesviruses.
AB  - The long-term treatment of herpesvirus infections with current antivirals in
      immunocompromised hosts leads to the development of drug-resistant viruses.
      Because nearly all currently available antivirals finally target viral DNA
      polymerase, virus resistant to one drug often shows cross-resistance to other
      drugs. In addition, nearly all the antivirals show various kinds of side effects
      or poor bioavailability. This evidence highlights the need for developing new
      antivirals for herpesviruses that have the different viral targets. Recently,
      high-throughput screening of large compound collections for inhibiting specific
      viral enzymes, or in vitro cell culture assay, has identified several new
      antivirals that target different viral proteins. These include the inhibitors of
      helicase/primase complex, terminase complex, portal protein and UL97 protein
      kinase. In addition, non-nucleoside inhibitors for viral DNA polymerase have been
      also developed. This review will focus on these new compounds that directly
      inhibit viral replication.

PMID- 14968937
TI  - Mechanism of antiviral activities of 3'-substituted L-nucleosides against 3TC
      resistant HBV polymerase: a molecular modelling approach.
AB  - Comparison of the active sites of the human HIV-1 reverse transcriptase (RT) and
      the homology-modelled hepatitis B virus (HBV) polymerase shows that the active
      sites of both enzymes are open to L-nucleosides, but the position where the 3'
      substituent of the L-ribose projects in HBV polymerase is wider and deeper than
      HIV-1 RT, which enables the HBV polymerase to accommodate various 3'-substituted
      L-nucleosides. However, the space is not sufficient to accommodate a bulky 3'
      substituent such as the 3'-azido group of L-3'-azido-3'-deoxythymidine. Analysis
      of the minimized structure of rtM204V HBV polymerase/3TCTP complex shows that,
      instead of the steric stress produced by rtV204, a loss of the van der Waals
      contact around the oxathiolane sugar moiety of 3TCTP caused by the mutation
      results in the disruption of the active site. Therefore, nucleosides, which are
      stabilized by additional specific interaction with the enzyme residues, can have
      more opportunities to circumvent the destabilization by the loss of hydrophobic
      interaction conferred by mutation. Specifically, the substitution at the 3'
      position would be beneficial as the HBV polymerase has wide open space composed
      of the highly conserved motif (YMDD) where the 3'-substituents of the L
      nucleosides project. As an example, our study shows that the 3'-fluorine atom
      contributes to the antiviral activity of L-3'-Fd4CTP against rtM204V HBV
      polymerase by readily compensating for the loss of the van der Waals interaction
      around the 2',3'-double bond through a formation of a hydrogen bond to the amide
      backbone of rtD205.

PMID- 14968938
TI  - Potent and selective inhibition of HIV and SIV by prostratin interacting with
      viral entry.
AB  - Prostratin, a non-tumour promoting phorbol ester, exhibit a potent anti-HIV
      activity against human immunodeficiency virus type 1 (HIV-1). However, the
      antiviral mechanism of prostratin is not well defined. In the present study, we
      report that prostratin exhibits potent antiviral activity against different
      strains of HIV-1 (subtypes B and D), a clinical HIV isolate (L1), HIV-2 (ROD and
      EHO) and SIV (MAC251) with EC50-values ranging from 0.02-0.09 microg/ml.
      Prostratin was equally active against HIV strains resistant to the polyanionic
      binding inhibitor dextran sulphate, the fusion inhibitor T-20 (enfuvirtide),
      nucleoside reverse transcriptase inhibitors (NRTIs) or protease inhibitors (PIs).
      In contrast, prostratin lost 4.4- and 6.8-fold of its effect against the HIV
      strains resistant to AMD3100 and the quaternary ammonium salt QAS10+,
      respectively. As shown by time-of-addition experiments, prostratin needs to be
      present at the time of viral adsorption to exert its antiviral activity. We
      selected an HIV strain (NL4.3/PROS) resistant to prostratin in MT-4 cells. The
      sensitivity of NL4.3/PROS towards prostratin, dextran sulphate and QAS10+ was
      reduced by 3.2, 4.1 and >50-fold, respectively. However, NL4.3/ PROS was still
      sensitive to AMD3100, T-20, NRTIs (zidovudine and nevirapine) and a PI
      (ritonavir). Recombination of the gp160-gene of the NL4.3/PROS strain in a NL4.3
      wild-type molecular clone fully rescued its phenotypic resistance. DNA sequencing
      of the NL4.3/PROS strain revealed mutations throughout the gp120 gene previously
      associated with resistance towards other HIV entry inhibitors. We concluded that
      prostratin inhibits the entry step of the replication cycle of HIV by interacting
      with a cellular target necessary for viral entry.

PMID- 14968940
TI  - Proton beams to replace photon beams in radical dose treatments.
AB  - With proton beam radiation therapy a smaller volume of normal tissues is
      irradiated at high dose levels for most anatomic sites than is feasible with any
      photon technique. This is due to the Laws of Physics, which determine the
      absorption of energy from photons and protons. In other words, the dose from a
      photon beam decreases exponentially with depth in the irradiated material. In
      contrast, protons have a finite range and that range is energy dependent.
      Accordingly, by appropriate distribution of proton energies, the dose can be
      uniform across the target and essentially zero deep to the target and the atomic
      composition of the irradiated material. The dose proximal to the target is lower
      compared with that in photon techniques, for all except superficial targets This
      resultant closer approximation of the planning treatment volume (PTV) to the
      CTV/GTV (grossly evident tumor volume/subclinical tumor extensions) constitutes a
      clinical gain by definition; i.e. a smaller treatment volume that covers the
      target three dimensionally for the entirety of each treatment session provides a
      clinical advantage. Several illustrative clinical dose distributions are
      presented and the clinical outcome results are reviewed briefly. An important
      technical advance will be the use of intensity modulated proton radiation
      therapy, which achieves contouring of the proximal edge of the SOBP (spread out
      Bragg peak) as well as the distal edge. This technique uses pencil beam scanning.
      To permit further progressive reductions of the PTV, 4-D treatment planning and
      delivery is required. The fourth dimension is time, as the position and contours
      of the tumor and the adjacent critical normal tissues are not constant. A
      potentially valuable new method for assessing the clinical merits of each of a
      large number of treatment plans is the evaluation of multidimensional plots of
      the complication probabilities for each of 'n' critical normal tissues/
      structures for a specified tumor control probability. The cost of proton therapy
      compared with that of very high technology photon therapy is estimated and
      evaluated. The differential is estimated to be approximately 1.5 provided there
      were to be no charge for the original facility and that there were sufficient
      patients for operating on an extended schedule (6-7 days of 14-16 h) with > or =
      two gantries and one fixed horizontal beam.

PMID- 14968941
TI  - Primary and secondary prevention in colorectal cancer.
AB  - Colorectal cancer is an important public health problem: there are nearly one
      million cases of colorectal cancer diagnosed worldwide each year and half a
      million deaths. The geographic distribution of colorectal cancer follows the
      division between westernized versus developing countries, The highest rates are
      in North America, Australia and Europe. Rates in Africa and Asia are low, but are
      increasing in countries adopting western-style dietary habits. Given that the
      majority of cancers occur in older people, and with the ageing of the population
      in mind, this observation adds impetus to investigating prevention strategies to
      avoid some of this increase. High vegetable and fruit consumption has been
      associated with decreased risk of colorectal cancer in numerous observational
      studies, while high fibre intake seems to have a similar effect. Promising data
      have been obtained for aspirin and other non-steroidal anti-inflammatory drugs,
      and dietary calcium. A physically active lifestyle and maintenance of normal body
      weight are behavioural tools for prevention of colorectal cancer. Faecal occult
      blood testing has been shown to be effective in the prevention of about 20% of
      deaths from colorectal cancer, but few population-based screening programs have
      been initiated. Sigmoidoscopy and colonoscopy are potentially effective screening
      modalities; however, no randomized trial data have yet been reported. Overall,
      primary and secondary prevention, chemoprevention and screening research and
      implementation of these prevention strategies are priorities for reduction of
      colorectal cancer incidence and mortality.

PMID- 14968942
TI  - Follow-up after colorectal cancer surgery.
AB  - Although most institutions offer some kind of follow-up to patients operated on
      for colorectal cancer, its value with respect to prolonged survival has been
      challenged. However, improved results of liver surgery and chemotherapy make it
      reasonable to assume that a follow-up programme leading to detection of more
      asymptomatic recurrences would result in improved survival. Liver metastases and
      extramural local recurrences are the most common secondary lesions and 5-year
      survival rates of about 30% are reported after radical resection. From these
      observations a survival benefit could be expected when follow-up is directed to
      these forms of recurrence. From six randomized studies, six comparative cohort
      studies and four meta-analyses it can be concluded that an intensive follow-up
      programme results in more recurrences being resected for cure and about a 10%
      higher 5-year survival rate compared with less intensive or no follow-up.
      However, the differences in the follow-up protocols make it difficult to conclude
      how a follow-up programme should be designed. Liver imaging and carcinoembryonic
      antigen assay should probably be included, while the yield of frequent
      colonoscopies is small. A follow-up regimen based on these principles is
      suggested. Future studies should focus on which tests are the most cost-effective
      for follow-up after colorectal cancer resection.

PMID- 14968943
TI  - Nordic 5-fluorouracil/leucovorin bolus schedule combined with oxaliplatin (Nordic
      FLOX) as first-line treatment of metastatic colorectal cancer.
AB  - This study combined oxaliplatin with the Nordic bolus schedule of 5-fluorouracil
      (5-FU) and folinic acid (FA) as first-line treatment in metastatic colorectal
      cancer. Twenty-seven patients were treated every second week with oxaliplatin 85
      mg/m2 as a 2-h infusion on day 1, followed by a 3-min bolus injection with 5-FU
      500 mg/m2 and 30 min later a bolus injection with FA 60 mg/m2 given on days 1 and
      2. Seventeen patients achieved a complete (n = 2) or partial (n = 15) response,
      leading to a confirmed response rate of 63% (95% CI 45-81%). The estimated median
      times to progression and survival were 8.9 and 18.7 months, respectively.
      Neutropenia grade 3-4 toxicity was seen in 63% of patients, neuropathy grade 3 in
      one patient and grade 2 in 12 patients. Oxaliplatin combined with the bolus
      Nordic schedule of 5-FU/ FA (Nordic FLOX) appears to be well tolerated, effective
      and feasible as first-line treatment of metastatic colorectal cancer yielding
      results comparable with those obtained by more complex schedules.

PMID- 14968944
TI  - Short-time infusion of oxaliplatin (Eloxatin) in combination with capecitabine
      (Xeloda) in patients with advanced colorectal cancer.
AB  - Neuropathy exacerbated by exposure to cold is a dose-limiting toxicity of
      oxaliplatin. The incidence of this side effect is claimed to dependent on
      infusion rate and therefore a 2-h infusion is often recommended. For practical
      reasons and for the convenience of the patient, we used XELOX (Xeloda 2000 mg/m2
      orally on days 1-14 and oxaliplatin 130 mg/m2 as a 30-min infusion on day 1) in
      patients with advanced colorectal cancer resistant to irinotecan and 5
      fluorouracil. Thirty-four consecutive patients received a median of 5 courses of
      XELOX. Nine patients obtained partial response (PR) (response rate (RR) 26%), 11
      patients no change (NC), 7 patients disease progression (PD) and 7 patients were
      not evaluable. Median time to progression was 4.7 (2.6-7.6) months and median
      survival was 7.4 (6.0-11.3) months. Sixteen patients had neuropathy grade 1, four
      patients grade 2 and two patients grade 3. Short-time infusion of oxaliplatin and
      capecitabine is an active and convenient second-line regimen with a safety
      profile similar to that of other oxaliplatin schedules.

PMID- 14968945
TI  - Circulating vascular endothelial growth factor six months after primary surgery
      as a prognostic marker in patients with colorectal cancer.
AB  - High preoperative circulating vascular endothelial growth factor (VEGF) is
      predictive of poor prognosis in patients with colorectal cancer (CRC). However,
      postoperative circulating VEGF has not yet been evaluated as a prognostic marker
      in CRC patients. In 318 consecutive patients who had undergone curative resection
      of primary CRC, the prognostic value of VEGF concentrations in plasma and serum
      obtained 6 months postoperatively was analysed and the results compared with the
      prognostic value of postoperative carcinoembryonic antigen (CEA) concentrations
      in matched serum samples. In univariate analyses, high serum and plasma VEGF ( >
      533 pg/ml and > 112 pg/ml, respectively) had no significant (p = 0.17 and p =
      0.13, respectively) impact on overall survival. On the contrary, high serum CEA (
      > 5 ng/ ml) was significantly (p < 0.0001) correlated to a poor prognosis.
      Finally, in multivariate analyses, the combination of high serum CEA and high
      serum VEGF was significantly (hazard ratio 3.0, p = 0.02) associated with poor
      survival compared to high serum CEA and low serum VEGF. It is concluded that 6
      months postoperatively serum CEA is a better prognostic marker than corresponding
      serum and plasma VEGF. However, high serum VEGF within high serum CEA was an even
      better predictor of overall survival than high serum CEA alone.

PMID- 14968946
TI  - Phagocytic activity and nitric oxide production of circulating polymorphonuclear
      leukocytes from patients with peritoneal carcinomatosis.
AB  - Many studies have demonstrated an increase of neutrophils in patients with
      advanced cancer. However, the possible role of increased neutrophils in various
      neoplasms studied to date varies considerably. The authors examined the changes
      in white blood cell counts in patients with peritoneal carcinomatosis.
      Malonildialdehyde and nitric oxide (NO) plasma and ascitic fluid levels,
      phagocitic activity and the ability of the polymorphonuclear cells (PMNCs) to
      produce nitric oxide were also measured. An increase in PMNCs and decrease in
      lymphocytes was found in cancer patients. Compared with healthy controls, cancer
      PMNCs showed significant enhancement of phagocytosis Similarly, pretreatment of
      healthy PMNCs with crude supernatants from short-term cultures of the peritoneal
      cells from ascitic fluid of patients with peritoneal carcinomatosis caused marked
      stimulation of PMNC phagocytosis. In addition, plasma and ascitic fluid nitric
      oxide levels in cancer patients were significantly higher than those found in
      control one. Most importantly, it was found that PMNCs from cancer patients
      release significantly more nitric oxide than corresponding normal controls.
      Therefore, considering the fact that neutrophils make up more than 50% of total
      leukocytes, these cells can play one of the most important roles in tumor
      biology.

PMID- 14968947
TI  - The clinical value of non-coplanar photon beams in biologically optimized
      intensity modulated dose delivery on deep-seated tumours.
AB  - The aim of the present study is to compare the merits of different
      radiobiologically optimized treatment techniques using few-field planar and non
      coplanar dose delivery on an advanced cancer of the cervix, with rectum and
      bladder as principal organs at risk. Classically, the rational for using non
      coplanar beams is to minimize the overlap of beam entrance and exit regions and
      to find new beam directions avoiding organs at risk, in order to reduce damage to
      sensitive normal tissues. Two four-beam configurations have been extensively
      studied. The first consists of three evenly spaced coplanar beams and a fourth
      non-coplanar beam. A second tetrahedral-like configuration, with two symmetric
      non-coplanar beams at the same gantry angle and two coplanar beams, with
      optimized beam directions, was also tested. The present study shows that when
      radiobiologically optimized intensity modulated beams are applied to such a
      geometry, only a marginal increase in the treatment outcome can be achieved by
      non-coplanar beams compared to the optimal coplanar treatment. The main reason
      for this result is that the high dose in the beam-overlap regions is already
      optimally reduced by biologically optimized intensity modulation in the plane.
      The large number of degrees of freedom already incorporated in the treatment by
      the use of intensity modulation and radiobiological optimization, leads to the
      saturation of the benefit acquired by a further increase in the degrees of
      freedom with non-coplanar beams. In conclusion, the use of coplanar
      radiobiologically optimized intensity modulation simplifies the dose delivery,
      reducing the need for non-coplanar beam portals.

PMID- 14968948
TI  - Determination and clinical verification of dose-response parameters for
      esophageal stricture from head and neck radiotherapy.
AB  - The purpose of this work is to determine the parameters and evaluate the
      predictive strength of the relative seriality model. This is accomplished by
      associating the calculated complication rates with the clinical follow-up
      records. The study is based on 82 patients who received radiation treatment for
      head and neck cancer. For each patient the 3D dose distribution delivered to the
      esophagus and the clinical treatment outcome were available. Clinical symptoms
      and radiological findings were used to assess the manifestation of radiation
      induced esophageal strictures. These data were introduced into a maximum
      likelihood fitting to calculate the best estimates of the parameters used by the
      relative seriality model (D50 = 68.4 Gy, gamma = 6.55, s = 0.22). The
      uncertainties of these parameters were also calculated and their individual
      influence on the dose-response curve was demonstrated. The best estimate of the
      parameters was applied to 58 patients of the study material and their esophageal
      stricture induction probabilities were calculated to illustrate the clinical
      utilization of the calculated parameters. The calculation of the biological
      effective dose (BED) appeared to be significantly sensitive to the applied
      fractionation correction for complex treatment plans. The relative seriality
      model was proved suitable in reproducing the treatment outcome pattern of the
      patient material studied (probability of finding a worse fit = 61.0%, the area
      under the ROC curve = 0.84 and chi2 test = 0.95). The analysis was carried out
      for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures
      are formed. Radiation-induced strictures were found to have a strong volume
      dependence (low relative seriality). The uncertainties of the parameters appear
      to have a significant supporting role on the estimated dose-response curve.

PMID- 14968949
TI  - Extracranial stereotactic radioablation: physical principles.
AB  - Extracranial stereotactic radioablation (ESR) involves treating well-demarcated
      targeted tissues (e.g. tumor with minimal margin for set-up uncertainties) with
      very large doses of radiation in single or a few fractions with the intent of
      causing profound late tissue damage within the targeted volume. In such
      circumstances, considerable effort must be taken to reduce non-target tissue
      exposure to the high dose levels in order to prevent late complications to
      involved organs. Consequently, the following conditions for effective delivery of
      the ESR techniques have to be satisfied: 1) delivery of a high dose per fraction,
      i.e. 10-24 Gy; 2) delivery of only a few fractions per course of treatment (e.g.
      1-4); 3) shaping of the prescription isodose surface conformally to the target
      surface; 4) delivery of a non-uniform dose distribution within the target with
      the highest dose in centrally located regions of hypoxia; 5) rapid fall-off of
      dose from the target volume to healthy tissue in all directions. In this paper it
      is shown that high doses per fraction in few fractions can be delivered to a
      variety of locations with both efficacy and acceptable toxicity (conditions 1 and
      2). Conformal shaping of the high isodose surfaces is best accomplished by
      employing many beams (5-10) each with carefully milled apertures precisely
      coincident with the target projection (condition 3). Beam intensity modulation
      creating parabolic beam entrance fluence profiles both concentrates the highest
      dose in central regions of tumor hypoxia and increases fall-off gradients outside
      of the target (conditions 4 and 5). It is also shown that isotropic, highly non
      coplanar beam arrangements avoiding oppositional fields allow more optimal fall
      off gradients to normal tissue as opposed to coplanar treatments (condition 5).

PMID- 14968950
TI  - New chemotherapy treatments in advanced cancer patients: an easily applicable
      evaluation of clinical efficacy and cost-effectiveness.
AB  - Novel cytostatic drugs have recently been introduced to treat advanced cancer
      patients. Although of only modest efficacy, their use is widespread, considerably
      increasing treatment costs. An easily applicable method to assess their efficacy
      and cost-effectiveness is needed. We have documented new cytostatic drugs whose
      consumption increased by over 60% from January 1998 to December 2000 in patients
      with advanced or metastatic cancer of the colorectum, lung (non-small cell),
      breast, ovary or brain. A review of the literature yielded 17 treatments that
      included these agents. For each regimen, we recorded six efficacy variables
      [median survival time (MS), survival rate at 1 year, absolute risk reduction,
      time to progression, quality of life (QoL), and patients needed to treat (NNT)].
      A four-point (A-D) efficacy (E) scale and a five-point (1-5) strength of evidence
      (SE) scale were applied. We obtained the cost differential of each regimen for a
      4-week treatment, cost per extra month of MS. and cost per NNT. One combination
      was rated with A efficacy (MS > 9 months+improved QoL) and nine with D (no MS or
      QoL improvement); 12 studies presented good quality (grade 1-2) evidence. The QoL
      of patients was significantly improved in only two regimens. The average cost
      differential was 1 311 Euro (all new regimens except one showed higher cost); the
      average cost per extra month of MS was 6 415 Euro; and treatment cost per NNT was
      87 767 Euro. Our method proved to be easy to apply, enabled comparisons with
      other treatments to be made and revealed that these very costly changes in
      clinical practice are not justified by available studies.

PMID- 14968951
TI  - Characterization of Campylobacter isolates recovered from clinically healthy pigs
      and from sporadic cases of campylobacteriosis in humans.
AB  - Campylobacter spp. were recovered from 660 (77.6%) of 850 swine cecal contents at
      the abattoir and from 24 (8.6%) of 278 specimens from sporadic cases of human
      diarrhea during the same period in the same geographical area. Campylobacter coli
      represented 95.7% of Campylobacter isolates recovered from pigs and 8.3% of those
      isolated from humans. Genetic profiles were determined by pulsed-field gel
      electrophoresis (PFGE) using KpnI enzyme to characterize the isolates in
      combination with phenotypic assays to detect production of cytotoxins,
      enterotoxins, and hemolysins. Among a subset of isolates (n = 10), up to five
      colonies from the same animal were characterized by PFGE. In 5 (50%) of 10 of the
      isolates, more than one genetic profile was observed per pig. Among the 100
      isolates from pigs selected for further analysis, 81 different genetic profiles
      were observed, whereas 20 different genetic profiles were found among the 24
      isolates of human origin. Cytotoxicity on Chinese hamster ovary cells was
      observed in 11 (11%) of 98 isolates from pigs and in 5 (21%) of 24 Campylobacter
      isolates from humans. No enterotoxin production was detected in Campylobacter
      isolates in this study, but 17 (71%) of 24 human and 61 (63%) of 97 pig isolates
      showed hemolytic activity. The study of genotypic and phenotypic profiles of
      swine and human isolates revealed no epidemiological relationship between
      isolates. The low genomic relatedness observed between groups of isolates and the
      weak toxicity level of swine isolates suggest that the hazard of contamination of
      humans by Campylobacter associated with swine production is low.

PMID- 14968952
TI  - Effect of intestinal content contamination on broiler carcass Campylobacter
      counts.
AB  - Intestinal contents may contaminate broiler carcasses during processing. The
      objective of this study was to determine what effect various levels of intestinal
      contents had on the numbers of Campylobacter detected in broiler carcass rinse
      samples. Eviscerated broiler carcasses were collected from the shackle line in a
      commercial processing plant immediately after passing through an inside/outside
      washer. Broiler carcasses were cut longitudinally into contralateral halves using
      a sanitized saw. Cecal contents from the same flock were collected, pooled,
      homogenized, and used to contaminate carcass halves. Paired carcass halves were
      divided into groups of eight each, and then cecal contents (2, 5, 10, 50, or 100
      mg) were placed onto one randomly selected half of each carcass, while the
      corresponding half of the same broiler carcass received no cecal contents.
      Campylobacter counts from carcass halves with cecal contamination were compared
      to the uncontaminated halves of the same carcasses using a paired t test. Carcass
      halves with 5 mg or more of surface cecal contamination had significantly higher
      numbers of Campylobacter than those without (P < 0.01). Carcass halves
      contaminated with only 5 mg of cecal contents had an average of 3.3 log CFU
      Campylobacter per ml of rinse, while corresponding uncontaminated carcass halves
      had 2.6 log CFU Campylobacter per ml of rinse. These data indicate that even
      small (5 mg) amounts of cecal contents can cause a significant increase in the
      numbers of Campylobacter on eviscerated broiler carcasses. Therefore, it is
      important to keep such contamination to a minimum during processing.

PMID- 14968953
TI  - Distribution and characterization of Campylobacter spp. from Russian poultry.
AB  - The distribution of Campylobacter spp. on 13 poultry farms (broiler chicken,
      quail, pheasant, peacock, and turkey) from eight regions (Vladimir, Vologda,
      Voronezh, Kaluga, Liptsk, Moscow, Orenburg, and Orel) in Russia was surveyed.
      Intestinal materials were plated onto Campylobacter-selective medium and plates
      were incubated microaerobically at 42 degrees C for 24 or 48 h. Identification
      was based on colonial morphology, microscopic examination, and biochemical tests;
      latex agglutination assays were used for confirmation. In total, 116 isolates
      were derived from 370 samples. Isolation rates were similar, regardless of
      whether the birds were from small or large broiler production farms.
      Susceptibility of 48 representative (from these production sources) strains of
      Campylobacter spp. to 38 antimicrobial compounds was determined by disk diffusion
      assays. All strains tested were sensitive to amikacin, gentamycin, sisomycin,
      chloramphenicol, imipenem, oleandomycin, erythromycin, azitromycin, and
      ampicillin. The strains were also sensitive to 100 microg/disk of carbenicillin,
      fluoroquinolones, and to nitrofurans. Fluoroquinolone sensitivity was most
      notable and may be related to its limited application in poultry production
      within Russia. Hippurate and ribosomal RNA gene primers were developed and used
      to distinguish Campylobacter jejuni and Campylobacter coli and to provide a
      measure of strain discrimination. The combination of PCR analysis and randomly
      amplified polymorphic DNA (RAPD) typing were conducted for selected isolates. The
      various poultry species and the different locations yielded Campylobacter
      isolates with discrete randomly amplified polymorphic DNA patterns. The
      distribution and substantial diversity of Campylobacter spp. isolates appears
      similar to that previously reported in other countries.

PMID- 14968954
TI  - Distribution of Escherichia coli O157:H7 in beef processed in a table-top bowl
      cutter.
AB  - Beef-processing equipment can be contaminated with pathogens such as Escherichia
      coli O157:H7 and Salmonella spp. The bowl cutter has wide application in particle
      size reduction and blending of meat products. This study was undertaken to
      determine (i) the distribution patterns of E. coli O157:H7 in equipment
      components and ground beef produced with a table-top bowl cutter under different
      operational conditions and (ii) the likelihood that pathogen contamination can be
      transferred to subsequent batches after a batch of beef contaminated with E. coli
      O157:H7 has been processed in the same bowl cutter. A beef trim (44.6 +/- 29.5 g)
      inoculated with 2 log CFU of an E. coli O157:H7 mutant strain resistant to
      rifampicin (E. coli O157:H7rif) was fed by hand into an uncontaminated beef-trim
      batch under two different batch sizes (2 and 4 kg), three processing times (60,
      120, and 240 s), and two feeding modes (running and stoppage fed). There were no
      significant differences (P > or = 0.05) among all the treatments for the averages
      of the counts of E. coli O157:H7rif distributed in the ground beef. Regardless of
      the processing time and the method used to feed the beef trims into the bowl
      cutter, the whole batch and the following subsequent batch became contaminated
      when previously contaminated beef was processed. Areas of the bowl cutter most
      likely to be contaminated with E. coli O157:H7 were (i) the material left on the
      top of the comb/knife guard and (ii) the knife. Material that overflowed the bowl
      cutter, when processing the batch with E. coli O157:H7rif, contaminated the
      equipment surroundings. A Pearson V probability distribution function was
      determined to describe the distribution of pathogenic organisms in the ground
      beef, a distribution that can also be applied when conducting process risk
      analyses on mixing-particle reduction operations for beef trims.

PMID- 14968955
TI  - Survival of Escherichia coli O157:H7 in set yogurt as influenced by the
      production of an exopolysaccharide, colanic acid.
AB  - Previous studies conducted in our laboratory revealed that Escherichia coli
      O157:H7 cells capable of producing colanic acid (CA), the acidic polysaccharide
      of mucoid slime, had increased tolerance to sublethal heat and the extreme pH of
      microbiological culture media. This study was undertaken to determine the effect
      of CA on the fate of E. coli O157:H7 during the processing and storage of an acid
      food: yogurt. Pasteurized and homogenized whole milk was inoculated with a wild
      type E. coli O157:H7, its CA-deficient mutant, or a mixture (1:1) of the two
      strains. Set yogurt was processed from the contaminated milk and stored at 4
      degrees and 15 degrees C for 3 weeks. Samples of milk and yogurt were withdrawn
      during processing and storage and analyzed for total plate counts and populations
      of E. coli O157:H7 and starter cultures. The results showed that E. coli O157:H7
      survived longer in yogurt stored at 15 degrees C than at 4 degrees C. Cells of E.
      coli O157:H7 deficient in CA production died off more rapidly than those of the
      parent strain. This suggests that CA plays a role in protecting cells of E. coli
      O157:H7 from stress during the processing and storage of set yogurt.

PMID- 14968956
TI  - Detection of Salmonella Senftenberg associated with high saline environments in
      mussel processing facilities.
AB  - A contamination by Salmonella Senftenberg in frozen mussels was detected in 1998
      during a routine analytical surveillance. From June 1998 to December 2001, a
      total of 3,410 samples of steamed frozen mussels and items related to their
      manufacture were analyzed for the presence of Salmonella. Salmonella Senftenberg
      was isolated in 573 (16.8%) samples, and no other serovar was detected. The
      contamination episodes extended for several months. Salmonella Senftenberg
      colonies from the first contamination events showed a rugose morphology on agar
      with a shiny crystalline layer and limited colony formation on microbiological
      media. These contaminations were mainly associated with brine (300 g of NaCl per
      liter), while the live molluscs that were being processed were free of
      Salmonella. When the brine contaminations were nearly controlled, new episodes
      were detected that were associated with live mussels. In the new episodes,
      colonies showed the typical characteristics of Salmonella and normal growth on
      agar. Salmonella Senftenberg presented a high resistance to unfavorable
      environments and showed a preference for clean environments. While Salmonella
      Senftenberg could be isolated from mussels after steam treatment, it could not
      survive after immersion in water at 80 degrees C for 1 min. This fact was used to
      develop a process to remove contamination from products, minimizing the health
      risk associated with frozen mussel consumption. The general incidence of
      Salmonella Senftenberg in facilities and mussels was reduced from 31.2% in 1998
      to 2.5% in 2001. During this study, no cases of illness from consumption of
      frozen mussels were reported, indicating a possible lack of virulence of
      Salmonella Senftenberg in these contamination events.

PMID- 14968957
TI  - Antimicrobial susceptibilities and epidemiological analysis of Salmonella
      enteritidis isolates in Korea by phage typing and pulsed-field gel
      electrophoresis.
AB  - A total of 81 isolates of Salmonella Enteritidis were analyzed by antibiotic
      susceptibility, phage typing, and pulsed-field gel electrophoresis (PFGE). Thirty
      two isolates came from broiler carcasses and pig feces, and 49 isolates were from
      humans in Seoul and suburbs of Seoul, Korea. Antibiotic resistance was most
      prevalent among human isolates. Of human isolates, 89.8% were resistant to more
      than two antibiotics, while 64.7% of poultry isolates and 13.3% of pig isolates
      showed multiple resistance to more than two antibiotics. The most common phage
      type (PT) was PT1, followed by PT30 or 33, PT21 and PT20a. The isolates showed
      six PFGE patterns with XbaI or SpeI digestion, and five PFGE patterns with NotI
      digestion. But a single pattern, PFGE X1, S1, or N1, was predominant and the rest
      of the PFGE patterns differed by only one or two bands. Results indicated the
      spread of a genetically related clone of Salmonella Enteritidis in foods and
      humans in Korea and that phage typing as well as PFGE may offer an improved level
      of discrimination for the epidemiological investigation of Salmonella
      Enteritidis.

PMID- 14968958
TI  - Evaluation of a 5'-nuclease (TaqMan) assay with the thin agar layer oxyrase
      method for the detection of Yersinia enterocolitica in ground pork samples.
AB  - A 5'-nuclease (TaqMan) assay was evaluated for its capability to recover and
      detect stressed Yersinia enterocolitica. Sensitivity studies of a 5'-nuclease
      assay for detecting Y. enterocolitica 0:8 in a pure culture system and spiked
      ground pork samples demonstrated that the assay has reliable sensitivity with a
      detection limit of 3 to 4 log CFU/ml or CFU/g. The PCR 5'-nuclease (TaqMan) assay
      was evaluated with the Thin Agar Layer Oxyrase method (TALO, overlaying 14 ml of
      Trypticase soy agar with a 1:30 dilution of "Oxyrase for Agar" onto a prepoured
      pathogen-specific, selective medium), and it was compared against the selective
      medium cefsulodin-irgasan-novobiocin (CIN) for recovering and detecting Y.
      enterocolitica from inoculated nonfrozen and frozen (-15 degrees C, 2 days)
      ground pork samples. The TALO method showed more sensitivity (detection limit, 2
      log CFU/ml), and it has greater recovery capability (0.5 to 1 log CFU/ml) than
      CIN (P < 0.05). The 5'-nuclease assay provided rapid detection processing (5
      versus 24 h after an 18-h enrichment). The sensitivity per PCR was calculated to
      as low as 0 to 1 log CFU per PCR reaction; however, in the method's current
      developmental stage, target pathogens should be enriched to 3 to 4 log CFU/ml or
      CFU/g to show consistent results. In a survey of 100 ground pork samples using
      TALO, CIN, and PCR methods, no Y. enterocolitica was recovered. A combined
      cultivation and an automated PCR TaqMan could be used as a presumptive screening
      test for detecting Y. enterocolitica in food samples.

PMID- 14968959
TI  - Hemolytic and proteolytic activities of Aeromonas hydrophila and Aeromonas
      veronii biovar sobria in broth and salmon extract at different temperatures.
AB  - Expression of hemolytic and proteolytic activities throughout the growth cycle
      was investigated with two enterotoxic aeromonad strains assigned to the species
      Aeromonas hydrophila and Aeromonas veronii biovar sobria. Although growth kinetic
      data were dependent on strain, temperature, and substrate, maximum populations
      attained were higher than 9 log CFU/ml in aerated tryptone soya broth plus yeast
      extract (TSBYE) and salmon extract within the range 4 to 28 degrees C. For both
      strains in TSBYE, variable amounts of hemolytic activity were first detected at
      any temperature when aeromonad counts were over 9 log CFU/ml. Afterwards, this
      activity increased up to similar levels (109 to 112 hemolytic units per ml)
      without a significant increase in populations. Salmon extract supported hemolysin
      synthesis at 28 but not 4 degrees C. Proteolytic activity of the A. hydrophila
      strain was only expressed in salmon extract at 28 degrees C, whereas A. veronii
      biovar sobria did at 28 degrees C in both substrates and at 10 degrees C in
      TSBYE.

PMID- 14968960
TI  - Cations reduce antimicrobial efficacy of lysozyme-chelator combinations.
AB  - Reduction of the antimicrobial efficacy of lysozyme-chelator combinations against
      two Escherichia coli O157:H7 strains on addition of mineral salts was studied.
      The objective of the study was to determine the effect of type and concentration
      of mono-, di-, and trivalent mineral salts on the antimicrobial effectiveness of
      lysozyme and various chelators against E. coli O157:H7. Seven salts (Al3+, Ca2+,
      Fe2+, Fe3+, K+, Mg2+, and Na+) at 1 to 10 mM were added to aqueous solutions of
      lysozyme and disodium ethylenediamine tetraacetic acid (EDTA), disodium
      pyrophosphate (DSPP), or pentasodium tripolyphosphate (PSTPP) at pH 6, 7, or 8
      and applied to cultures of E. coli O157:H7 strains 932 and H1730. Inhibitory
      activity of lysozyme chelator combinations against both strains was completely
      lost after addition of > or = 1 mM Ca2+ and Mg2+ at pH 7 and 8. At pH 6,
      antimicrobial activity of lysozyme-EDTA against both strains was retained in the
      presence of calcium or magnesium cations. DSPP-lysozyme inhibited strain H1730 at
      pH 6 despite the presence of Mg2+. Concentrations above 4 mM Fe2+ neutralized
      activity of all lysozyme-chelator combinations. Reversal of inhibition by
      lysozyme-chelator complexes by the monovalent Na+ and K+ ions depended on E. coli
      O157:H7 strain type. Neither monovalent cation reversed inhibition of strain 932.
      However, Na+ and K+ reversed lysozyme-chelator inhibition of strain H1730. The
      addition of > or = 1 mM Fe3+ or Al3+ was effective in reversing inhibition of
      both strains by lysozyme and EDTA at pH 6, 7, and 8. Isothermal titration
      calorimetry was used to determine the amount of ion-specific competitive binding
      of free cations by EDTA-lysozyme combinations. A mechanistic model for the
      antimicrobial functionality of chelator-lysozyme combinations is proposed.

PMID- 14968961
TI  - Prevalence of Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella in
      two geographically distant commercial beef processing plants in the United
      States.
AB  - For two large beef processing plants, one located in the southern United States
      (plant A) and one located in the northern United States (plant B), prevalence of
      Escherichia coli O157:H7, Listeria spp., Listeria monocytogenes, and Salmonella
      was determined for hide, carcass, and facility environmental samples over the
      course of 5 months. The prevalence of E. coli O157:H7 (68.1 versus 55.9%) and
      Salmonella (91.8 versus 50.3%) was higher (P < 0.05), and the prevalence of
      Listeria spp. (37.7 versus 75.5%) and L. monocytogenes (0.8 versus 18.7%) was
      lower (P < 0.05) for the hides of cattle slaughtered at plant A versus plant B.
      Similarly, the prevalence of Salmonella (52.0 versus 25.3%) was higher (P < 0.05)
      and the prevalence of Listeria spp. (12.0 versus 40.0%) and L. monocytogenes (1.3
      versus 14.7%) was lower (P < 0.05) for the fence panels of the holding pens of
      plant A versus plant B. The prevalence of E. coli O157:H7 (3.1 versus 10.9%),
      Listeria spp. (4.5 versus 14.6%), and L. monocytogenes (0.0 versus 1.1%) was
      lower (P < 0.05) for preevisceration carcasses sampled at plant A versus plant B.
      Salmonella (both plants), Listeria spp. (plant B), and L. monocytogenes (plant B)
      were detected on fabrication floor conveyor belts (product contact surfaces) late
      during the production day. For plant B, 21 of 148 (14.2%) late-operational
      fabrication floor conveyor belt samples were L. monocytogenes positive. For plant
      B, E. coli O157:H7 and L. monocytogenes were detected in preoperational
      fabrication floor conveyor belt samples. Overall results suggest that there are
      regional differences in the prevalence of pathogens on the hides of cattle
      presented for harvest at commercial beef processing plants. While hide data may
      reflect the regional prevalence, the carcass data is indicative of differences in
      harvest practices and procedures in these plants.

PMID- 14968962
TI  - Protocol for evaluating the efficacy of cetylpyridinium chloride as a beef hide
      intervention.
AB  - The objective of this study was to establish the necessary protocols and assess
      the efficacy of cetylpyridinium chloride (CPC) as an antimicrobial intervention
      on beef cattle hides. Experiments using CPC were conducted to determine (i) the
      methods of neutralization needed to obtain valid efficacy measurements, (ii) the
      effect of concentration and dwell time after treatment, (iii) the effect of CPC
      on hide and carcass microbial populations when cattle were treated at a feedlot
      and then transported to a processing facility for harvest, and (iv) the
      effectiveness of spray pressure and two-spray combinations of CPC and water to
      reduce hide microbial populations. Residual CPC in hide sponge samples prevented
      bacterial growth. Dey-Engley neutralization media at 7.8% and a centrifugation
      step were necessary to overcome this problem. All dwell times, ranging from 30 s
      to 4 h, after 1% CPC application to cattle hides resulted in aerobic plate counts
      and Enterobacteriaceae counts 1.5 log CFU/100 cm2 lower than controls. The most
      effective dose of CPC was 1%, which reduced aerobic plate counts and
      Enterobacteriaceae counts 2 and 1 log CFU/100 cm2, respectively. Low-pressure
      application of 1% CPC at the feedlot, transport to the processing facility, and
      harvest within 5 h of application resulted in no effect on Escherichia coli O157
      prevalence on hides or preevisceration carcasses. Two high-pressure CPC washes
      lowered aerobic plate counts and Enterobacteriaceae counts by 4 log CFU/100 cm2,
      and two medium-pressure CPC washes were only slightly less effective. These
      results indicate that under the proper conditions, CPC may still be effective for
      reducing microbial populations on cattle hides. Further study is warranted to
      determine if this effect will result in reduction of hide-to-carcass
      contamination during processing.

PMID- 14968963
TI  - Effects of cetylpyridinium chloride, acidified sodium chlorite, and potassium
      sorbate on populations of Escherichia coli O157:H7, Listeria monocytogenes, and
      Staphylococcus aureus on fresh beef.
AB  - The effects of selected food-grade antimicrobial agents at decreasing the number
      of pathogenic bacteria on fresh beef were determined. Beef cubes inoculated with
      Escherichia coli O157:H7, Listeria monocytogenes, or Staphylococcus aureus were
      sprayed with 0.5% cetylpyridinium chloride (CPC), 0.12% acidified sodium chlorite
      (ASC), 0.1% potassium sorbate (PS), or an equal mix of any two solutions. The
      beef samples were placed on absorbent tray pads sprayed with each single or mixed
      solution, wrapped with polyvinyl chloride film, heat sealed, and stored at 4
      degrees C for 2 weeks. Surface sanitization using CPC, ASC, or an equal mix of
      these two agents effectively reduced microbial numbers on the beef during
      storage. At day 0, ASC and the CPC-ASC mix reduced the number of E. coli O157:H7
      by 2.50 and 1.58 log CFU/cm2, respectively. CPC demonstrated a 3.25-log reduction
      of L. monocytogenes and a 4.70-log reduction of S. aureus at 14 days. The CPC-PS
      mix reduced E. coli O157:H7 numbers by 1.46, L. monocytogenes by 2.95, and S.
      aureus by 4.41 log CFU/cm2 at 14 days. PS alone and the mixed solutions, CPC-ASC,
      CPC-PS, or ASC-PS, were not as effective as ASC or CPC alone. To effectively
      reduce E. coli O157:H7, L. monocytogenes, or S. aureus numbers, higher (> 0.1%)
      concentrations of PS were necessary. Loss of redness and light color of beef
      surfaces consistently coincided with decreases in pH for ASC-treated beef
      samples.

PMID- 14968964
TI  - Changes in heat resistance resulting from pH and nutritional shifts of acid
      adapted and non-acid-adapted Listeria monocytogenes Scott A.
AB  - Stationary-phase Listeria monocytogenes cells that were either pH dependent acid
      adapted or not acid adapted were heat challenged at 60 degrees C in a two-level
      full factorial design for three variables. The three variables and the levels
      consisted of tryptic soy broth (TSB) and sterile cell-free culture supernatant
      (sterile TSB), the presence and absence of 1% added glucose, and pH 4.8 and pH 7.
      Non-acid-adapted cells were most heat resistant when challenged in TSB (mean
      decimal reduction times at 60 degrees C: D60 = 1.16 min). In the absence of added
      glucose, non-acid-adapted cells had similar D60-values for inactivations at pH
      4.8 and pH 7; however, the presence of glucose caused non-acid-adapted cells
      challenged at pH 4.8 to be more heat sensitive (D60 = 0.65 min) than those
      inactivated at pH 7 (D60 = 1.03 min), indicating an interaction between glucose
      and pH. Overall, the significantly decreased heat resistance of the acid-adapted
      cells was due to the presence of glucose (D60 = 0.78 min without glucose, D60 =
      0.59 min with glucose). Acid-adapted cells heat challenged in TSB had similar D60
      values for inactivations at pH 4.8 and pH 7; however, acid-adapted cells in
      sterile TSB challenged at pH 4.8 (D60 = 0.52 min) had significantly lower heat
      resistance than did cells challenged at pH 7 (D60 = 0.76 min), indicating an
      interaction between the medium and pH. The L. monocytogenes survivor data were
      modeled to extract information on the frequency distribution of heat resistance
      within heat-challenged populations, and the frequency distribution
      characteristics of mean, mode, and variance were compared among treatment
      conditions. Significant differences in the frequency distribution data were
      compared with the D60-values. These data indicated that the presence and level of
      cross-protection is highly dependent on the physiological state of the cells and
      nutrient availability at the time of heat challenge. Such conditions should be
      considered to ensure that stressed pathogens in foods are destroyed or
      inactivated.

PMID- 14968965
TI  - Behavior of Listeria monocytogenes in a Pseudomonas putida biofilm on a
      condensate-forming surface.
AB  - Listeria monocytogenes has been isolated from condensate-forming surfaces in food
      processing plants. The objective of this research was to observe the behavior of
      L. monocytogenes on condensate-covered stainless steel with a Pseudomonas putida
      biofilm. L. monocytogenes-containing biofilms, either with or without added
      chicken protein, were incubated in a high humidity chamber at 12 degrees C to
      allow formation of condensate. Samples were analyzed for attached and unattached
      L. monocytogenes and total plate count periodically for 35 days. Samples were
      also taken for microscopic observation of Listeria and bacterial extracellular
      polymeric substances (EPS). L. monocytogenes attached in significantly greater
      numbers (> 3-log difference) to surfaces with preexisting P. putida biofilms than
      to Pseudomonas-free surfaces. L. monocytogenes survived in the presence or
      absence of P. putida with no added nutrients for 35 days, with numbers of
      survivors in the range of 3 to 4 log CFU/cm2 in the presence of P. putida and
      less than 2.9 log CFU/cm2 in pure culture. Attached and unattached L.
      monocytogenes were at similar levels throughout the incubation under all
      conditions studied. The addition of protein to the biofilms allowed growth of L.
      monocytogenes in pure culture during the first 7 days of incubation. Numbers of
      L. monocytogenes were not affected by the presence of P. putida when protein was
      present. Unattached L. monocytogenes were at levels of 3.6 to 6.7 log CFU/cm2 on
      the protein-containing surfaces. Microscopic observation of the condensate
      covered biofilms indicated that L. monocytogenes formed microcolonies embedded
      within an EPS matrix over a 28-day period. This research demonstrates that L.
      monocytogenes can survive on condensate-forming stainless steel in low and high
      nutrient conditions, with or without the presence of Pseudomonas biofilm. The
      Listeria can detach and, therefore, have the potential to contaminate product.

PMID- 14968966
TI  - Tracking of Listeria monocytogenes in smoked fish processing plants.
AB  - Four smoked fish processing plants were used as a model system to characterize
      Listeria monocytogenes contamination patterns in ready-to-eat food production
      environments. Each of the four plants was sampled monthly for approximately 1
      year. At each sampling, four to six raw fish and four to six finished product
      samples were collected from corresponding lots. In addition, 12 to 14
      environmental sponge samples were collected several hours after the start of
      production at sites selected as being likely contamination sources. A total of
      234 raw fish, 233 finished products, and 553 environmental samples were tested.
      Presumptive Listeria spp. were isolated from 16.7% of the raw fish samples, 9.0%
      of the finished product samples, and 27.3% of the environmental samples. L.
      monocytogenes was isolated from 3.8% of the raw fish samples (0 to 10%, depending
      on the plant), 1.3% of the finished product samples (0 to 3.3%), and 12.8% of the
      environmental samples (0 to 29.8%). Among the environmental samples, L.
      monocytogenes was found in 23.7% of the samples taken from drains, 4.8% of the
      samples taken from food contact surfaces, 10.4% of the samples taken from
      employee contact surfaces (aprons, hands, and door handles), and 12.3% of the
      samples taken from other nonfood contact surfaces. Listeria spp. were isolated
      from environmental samples in each of the four plants, whereas L. monocytogenes
      was not found in any of the environmental samples from one plant. Overall, the L.
      monocytogenes prevalence in the plant environment showed a statistically
      significant (P < 0.0001) positive relationship with the prevalence of this
      organism in finished product samples. Automated EcoRI ribotyping differentiated
      15 ribotypes among the 83 L. monocytogenes isolates. For each of the three plants
      with L. monocytogenes-positive environmental samples, one or two ribotypes seemed
      to persist in the plant environment during the study period. In one plant, a
      specific L. monocytogenes ribotype represented 44% of the L. monocytogenes
      positive environmental samples and was also responsible for one of the two
      finished product positives found in this plant. In another plant, a specific L.
      monocytogenes ribotype persisted in the raw fish handling area. However, this
      ribotype was never isolated from the finished product area in this plant,
      indicating that this operation has achieved effective separation of raw and
      finished product areas. Molecular subtyping methods can help identify plant
      specific L. monocytogenes contamination routes and thus provide the knowledge
      needed to implement improved L. monocytogenes control strategies.

PMID- 14968967
TI  - Increased inactivation of ozone-treated Clostridium perfringens vegetative cells
      and spores on fabricated beef surfaces using mild heat.
AB  - Ozone treatment of beef surfaces enhanced the effectiveness of cooking
      temperatures ranging from 45 to 75 degrees C against enterotoxin-producing
      strains of Clostridium perfringens. Vegetative cells on beef surfaces at an
      initial concentration of 5.59 +/- 0.17 log CFU/g were reduced significantly (P <
      0.05) to 4.09 +/- 0.72 log CFU/g and 3.50 +/- 0.90 log CFU/g after combined
      treatments with aqueous ozone (5 ppm) and subsequent heating at 45 and 55 degrees
      C, respectively. Spores on the beef surface were likewise significantly reduced
      from an initial concentration of 2.94 +/- 0.37 log spores per g to 2.07 +/- 0.38
      log spores per g and 1.70 +/- 0.37 log spores per g after the combined treatment
      with aqueous ozone (5 ppm) and subsequent heating at 55 and 75 degrees C,
      respectively. Fluorescent nucleic acid stains were used with confocal
      fluorescence microscopy to show that spores remaining attached to the meat were
      protected from treatment-specific injury. This study provides evidence for the
      decreased resistance of both vegetative cells and spores of C. perfringens with
      ozone treatment that is followed by heat treatment at temperatures that would not
      otherwise be as effective, thus lowering the requirements for cooking beef while
      maintaining a margin of safety.

PMID- 14968968
TI  - Control of bacterial pathogens during processing of cold-smoked and dried salmon
      strips.
AB  - Microbiological and chemical changes were determined during the smoking and
      drying of salmon strips processed at 29 to 31 degrees C for 4 days at a facility
      in Alaska in 1993. During the process, Staphylococcus aureus populations
      increased to more than 10(5) CFU/g after 2 to 3 days of processing. Subsequent
      laboratory studies showed that a pellicle (dried skinlike surface) formed rapidly
      on the strips when there was rapid air circulation in the smokehouse and that
      bacteria embedded in or under the pellicle were able to grow even when heavy
      smoke deposition occurred. Under these conditions, an inoculum of 26 CFU/g of S.
      aureus increased to 10(5) CFU/g after 3 days of processing. Elimination of
      preprocess drying and reduction in air flow during smoking resulted in smoke
      deposition before pellicle formation and enabled the product to reach levels of
      water-phase salt and water activity that inhibit the growth of S. aureus and
      Listeria monocytogenes. In 1994, these modifications were then applied during
      processing at an Alaskan facility, and S. aureus could not be detected in the
      finished product. L. monocytogenes was detected in the raw product area, on the
      processing tables, and on the raw salmon strips, but it was not detected in the
      finished product when the smoke was applied before pellicle formation.

PMID- 14968969
TI  - Effect of cooling on Clostridium perfringens in pea soup.
AB  - Foods associated with Clostridium perfringens outbreaks are usually abused after
      cooking. Because of their short generation times, C. perfringens spores and cells
      can grow out to high levels during improper cooling. Therefore, the potential of
      C. perfringens to multiply in Dutch pea soup during different cooling times was
      investigated. Tubes of preheated pea soup (50 degrees C) were inoculated with
      cocktails of cells or heat-activated spores of this pathogen. The tubes were
      linearly cooled to 15 degrees C in time spans of 3, 5, 7.5, and 10 h and were
      subsequently stored in a refrigerator at 3 or 7 degrees C for up to 84 h. Cell
      numbers increased by 1-log cycle during the 3-h cooling period and reached their
      maximum after 10 h of cooling. Subsequent refrigeration hardly reduced cell
      numbers. Cooling of 3.75 liters of pea soup in an open pan showed that this
      amount of pea soup cooled from 50 to 15 degrees C in 5 h, which will allow a more
      than 10-fold increase in cell numbers. These findings emphasize the need of good
      hygienic practices and quick cooling of heated foods after preparation.

PMID- 14968970
TI  - Enumeration of yeasts in dairy products: a comparison of immunological and
      genetic techniques.
AB  - Enzyme-linked immunosorbent assay (ELISA) and PCR techniques have been developed
      for the detection of spoilage yeast species in dairy products. Polyclonal
      antibodies against live yeast cells (AY) were raised in rabbits by inoculation of
      a mixture of 10 yeast species frequently associated with dairy products spoilage.
      AY antibodies were used for the development of two ELISA formats (indirect and
      double-antibody sandwich ELISA) for the detection of yeast species in milk and
      yogurt. A PCR assay was also developed for yeast detection in dairy products,
      using primers designed to amplify a conserved 250-base pair fragment of the 18S
      rRNA of the yeast species. The results obtained in this work show that ELISA
      techniques using polyclonal antibodies against viable yeast cells are of limited
      value for the detection and enumeration of spoilage yeast species in dairy
      products. On the contrary, PCR amplification of a conserved region of the 18S
      rRNA of the yeast species allows the homogeneous detection of all the yeast
      species tested and, combined with an overnight enrichment of samples, could be
      used for the detection of low levels of viable spoilage yeast species in dairy
      products.

PMID- 14968971
TI  - Fate of maize intrinsic and recombinant genes in calves fed genetically modified
      maize Bt11.
AB  - The presence of maize intrinsic and recombinant cry1Ab genes in the
      gastrointestinal (GI) contents, peripheral blood mononuclear cells (PBMC), and
      visceral organs of calves fed genetically modified Bt11 maize was examined by PCR
      in a subchronic 90-day performance study. Samples were collected from six
      Japanese Black/Holstein calves fed Bt11 maize and from six calves fed non-Bt
      maize. Fragments of maize zein (Ze1), invertase, chloroplast, and cry1Ab were
      detected inconsistently in the rumen fluid and rectal contents 5 and 18 h after
      feeding. The chloroplast DNA fragments of ribulose-1,5-bisphosphate
      carboxylase/oxygenase and tRNA were detected inconsistently in the PBMC, the
      visceral organs, and the longissimus muscle, while the cry1Ab gene was never
      detected in PBMC or in the visceral organs. These results suggest that feed
      derived maize DNA was mostly degraded in the GI tract but that fragmented DNA was
      detectable in the GI contents as a possible source of transfer to calf tissues.
      These results also suggest that the recombinant cry1Ab genes were not transferred
      to the PBMC and tissues of calves fed Bt11 maize.

PMID- 14968972
TI  - Inactivation of Salmonella typhimurium and Escherichia coli O157:H7 in apple
      juice by a combination of nisin and cinnamon.
AB  - Pasteurized apple juice with nisin (0, 25, 50, 100, and 200 ppm, wt/vol) and
      cinnamon (0 and 0.3%, wt/vol) was inoculated with Salmonella Typhimurium and
      Escherichia coli O157:H7 at 10(4) CFU/ml and stored at 5 and 20 degrees C. Counts
      on tryptic soy agar (TSA), selective medium (xylose Lysine desoxycholate agar for
      Salmonella Typhimurium, and MacConkey sorbitol agar for E. coli O157:H7), and
      thin agar layer (TAL) were determined at 1 h and 1, 3, 7, and 14 days. The TAL
      method (selective medium overlaid with TSA) was used for recovery of sublethally
      injured cells. The pathogens were gradually inactivated by the acidic pH of apple
      juice. Nisin and cinnamon greatly contributed to the inactivation. The killing
      effect was more marked at 20 degrees C, with counts in all treated samples being
      undetectable by direct plating in 3 days for Salmonella Typhimurium and 7 days
      for E. coli O157:H7. Thus, several factors influenced the decrease in counts: low
      pH, addition of nisin and cinnamon, and storage temperature. The TAL method was
      as effective as TSA in recovering injured cells of the pathogens. The combination
      of nisin and cinnamon accelerates death of Salmonella Typhimurium and E. coli
      O157:H7 in apple juice and so enhances the safety of the product.

PMID- 14968973
TI  - Survival of Listeria monocytogenes in vanilla-flavored soy and dairy products
      stored at 8 degrees C.
AB  - The survival of Listeria monocytogenes V37 in vanilla-flavored yogurt (low-fat
      and nonfat) and soy milk (low-fat and Plus) stored at 8 degrees C for 31 days was
      investigated. Commercial samples of yogurt and soy milk were used. These samples
      were inoculated with either 10(4) or 10(7) CFU of L. monocytogenes per ml.
      Sampling was carried out every 3 to 4 days initially and was then carried out
      weekly, for a total storage time of 31 days. Each time a sample was collected,
      the pH of the sample was measured. After 31 days, low-fat plain, low-fat vanilla,
      and nonfat plain yogurt samples inoculated with 10(4) CFU/ml showed 2.5-log
      reductions in viable cell populations, and nonfat vanilla yogurt showed a 3.5-log
      reduction. For yogurt inoculated with 10(7) CFU/ml, reductions of 2.5 log CFU/ml
      were observed for plain low-fat and nonfat yogurts, and reductions of 5 log
      CFU/ml were observed for vanilla-flavored low-fat and nonfat yogurts. In vanilla
      flavored and plain low-fat and Plus soy milk samples, cell counts increased from
      10(4) and 10(7) CFU/ml to 10(9) CFU/ml at 7 and 3 days of storage, respectively,
      at 8 degrees C. Coagulation in soy milk samples was observed when the cell
      population reached 10(9) CFU/ml. In soy milk, the L. monocytogenes population did
      not change for up to 31 days. Vanillin had an inhibitory effect on L.
      monocytogenes in yogurt but not in soy milk.

PMID- 14968974
TI  - Thermal inactivation of Listeria innocua in salmon (Oncorhynchus keta) caviar
      using conventional glass and novel aluminum thermal-death-time tubes.
AB  - Differences in the come-up times and thermal inactivation parameters of Listeria
      innocua in salmon (Oncorhynchus keta) caviar containing 2.5% salt using
      conventional thermal-death-time (TDT) glass tubes and a novel aluminum tube were
      tested and compared. Generally, the come-up times and decimal reduction times (D
      values) were shorter and the change in temperature required to change the D-value
      (z-value) was longer in the aluminum than in the glass tubes. The D-values at 60,
      63, and 65 degrees C for the aluminum TDT tubes were 2.97, 0.77, and 0.40 min,
      respectively, and for the glass TDT tubes, these values were 3.55, 0.84, and 0.41
      min. The z-values were 5.7 degrees C in the aluminum and 5.3 degrees C in the
      glass. Because of the shorter come-up time, the aluminum TDT tubes may provide a
      more precise measurement of microbial thermal inactivation than the glass TDT
      tubes, particularly for viscous materials, solid foods, and foods containing
      particulate matter.

PMID- 14968975
TI  - A colony blot immunoassay for the rapid identification of Bacillus cereus.
AB  - A colony blot immunoassay was developed for the rapid identification of Bacillus
      cereus using antibodies against the 28.5-kDa cell-surface antigen of B. cereus.
      Suspect colonies from plates were blotted onto a Whatman #541 membrane, dried,
      and fixed by UV irradiation. The membrane was then immersed in an anti-B. cereus
      antibody-horseradish peroxidase conjugate for 60 min. After washing and reacting
      with 4-chloro-1-naphthol and H2O2, the appearance of purple spots indicated the
      presence of B. cereus. This assay effectively identified 61 of 62 B. cereus
      strains tested. Among 38 non-B. cereus strains, which were other Bacillus spp.
      (19 genera), 36 gave true-negative results, and 2 showed false-positive results.
      The sensitivity and specificity for B. cereus were 98.4 and 94.7%, respectively.
      The present assay is easy to use, and the rapid identification of B. cereus can
      be completed in 2.5 h.

PMID- 14968976
TI  - The potential application of vanillin in preventing yeast spoilage of soft drinks
      and fruit juices.
AB  - The preservative effect of vanillin, the major constituent of vanilla beans, was
      studied in an apple juice and peach-flavored soft drink. Vanillin activity was
      tested against Saccharomyces cerevisiae and Candida parapsilosis at 8 and 25
      degrees C over an 8-week storage period. Initial results in laboratory media
      indicated minimum inhibitory concentration values of 17 and 9 mM vanillin for the
      two yeast strains. Concentrations of 20 and 10 mM vanillin, respectively, were
      required to achieve complete inhibition of both yeast strains inoculated at a
      level of approximately 10(4) CFU/ml in the apple juice and peach-flavored soft
      drink over the 8-week storage at 25 degrees C. These effective levels were
      reduced to 5 and 1 mM, when the storage temperature was reduced to 8 degrees C. A
      biocidal effect against both yeasts was observed within 96 h to 8 weeks, with
      vanillin concentrations of 5 to 40 mM depending on the beverage and the storage
      temperatures used. The increased activity of vanillin in the peach-flavored soft
      drink (pH 3.1) in comparison to the apple juice (pH 3.5) is probably a result of
      the lower intrinsic pH of the former; however, variation in vitamin and mineral
      levels or the presence of other phenolic compounds between the two drinks might
      also have contributed to the observed differences. Furthermore, the increased
      activity at the lower temperature could be linked to the combination of the
      increased membrane fluidity and the membrane-perturbing action of vanillin. We
      conclude that vanillin has the potential to preserve fruit juices and soft drinks
      that are low in both lipid and protein content against S. cerevisiae and C.
      parapsilosis.

PMID- 14968977
TI  - Antimicrobial activity of a low-molecular-weight chitosan obtained from cellulase
      digestion of chitosan.
AB  - A water-soluble chitosan hydrolysate with high activity against Escherichia coli
      was obtained during cellulase digestion of chitosan for 18 h. This 18-h
      hydrolysate is composed of low-molecular-weight chitosan (LMWC), with a molecular
      weight of 12.0 kDa, and chitooligosaccharides, which are composed of sugars with
      a degree of polymerization of 1 to 8. LMWC has a strong activity at 100 ppm
      against many pathogens and yeast species, including Bacillus cereus, E. coli,
      Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella enterica serovar Typhi,
      and Saccharomyces cerevisiae, while the chitooligosaccharides have much weaker
      antimicrobial activity than does LMWC. Accordingly, the antimicrobial activity
      against E. coli in the 18-h hydrolysate proved to come mainly from the presence
      of LMWC.

PMID- 14968978
TI  - Factors contributing to the occurrence of antimicrobial drug residues in Kenyan
      milk.
AB  - The study investigated factors contributing to the occurrence of antimicrobial
      drug residues in milk within four major milk production districts in Kenya. The
      frequency of contamination was studied among small- and large-scale dairy
      producers to determine if there were differences between the two types of
      producers. Field samples (n = 1,600) were analyzed with the improved Dutch tube
      diffusion test, a microbial inhibitor test (Bacillus stearothermophilus). In
      total, 144 and 64 samples from small- and large-scale producers, respectively,
      were found to contain beta-lactam antibiotics at levels exceeding the established
      Codex maximum residue level for penicillin G (4 microg/kg). The difference in
      results between the two categories of producers was found to be significant (P <
      0.001). To explain the higher frequency of antibiotic contamination of milk from
      small-scale producers, a questionnaire was constructed and used with 220 randomly
      selected smallholders in the selected districts. The results suggested (i) lack
      of understanding of risks related to antibiotic contamination of food, (ii) poor
      or no treatment records, and (iii) lack of a monitoring system as major risks for
      contamination. It was concluded that intensification of the education among small
      scale dairy producers would greatly reduce the occurrence of antimicrobial
      residues in milk.

PMID- 14968979
TI  - Changes in galactose and lactic acid content of sweet whey during storage.
AB  - Whey is often stored or transported for a period of time prior to processing.
      During this time period, galactose and lactic acid concentrations may accumulate,
      reducing the quality of spray-dried whey powders in regard to stickiness and
      agglomeration. This study surveyed industry samples of Cheddar and mozzarella
      cheese whey streams to determine how galactose and lactic acid concentrations
      changed with storage at appropriate (4 degrees C) and abuse (37.8 degrees C)
      temperatures. Samples stored at 4 degrees C did not exhibit significant increases
      in levels of lactic acid or galactose. Mozzarella whey accumulated the greatest
      amount of galactose and lactic acid with storage at 37.8 degrees C. Whey samples
      derived from cheese made from single strains of starter culture were also
      evaluated to determine each culture's contribution to galactose and lactic acid
      production. Starter cultures evaluated included Streptococcus salivarius ssp.
      thermophilus. Lactobacillus helveticus, Lactobacillus delbrueckii ssp.
      bulgaricus, Lactococcus lactis ssp. cremoris, and Lactococcus lactis ssp. lactis.
      Whey derived from L. helveticus accumulated a significantly greater amount of
      lactic acid upon storage at 37.8 degrees C as compared with the other cultures.
      Galactose accumulation was significantly decreased in whey from L. lactis ssp.
      lactis stored at 37.8 degrees C in comparison with the other cultures. Results
      from this study indicate that proper storage conditions (4 degrees C) for whey
      prevent accumulation of galactose and lactic acid while the extent of
      accumulation during storage at 37.8 degrees C varies depending on the culture(s)
      used in cheese production.

PMID- 14968980
TI  - Histamine-related hygienic qualities and bacteria found in popular commercial
      scombroid fish fillets in Taiwan.
AB  - To determine the histamine-related hygienic qualities and bacteria of scombroid
      fish fillets sold in traditional retail markets, 61 samples were collected from
      northern and southern Taiwan. It was found that the content of volatile base
      nitrogen in most samples was below 25 mg/100 g, which is the regulatory level in
      Taiwan. The ratio of unacceptable samples/total samples for aerobic plate count
      and Escherichia coli was 100% and 15% in northern samples and 100% and 20% in
      southern samples, respectively, compared with the requirements of hygienic
      standards. The average content of various biogenic amines in all samples were
      lower than 3 mg/100 g, except for histamine average content (4.6 mg/100 g) in
      southern samples. Among southern samples, four samples contained 12.8 to 28.8
      mg/100 g histamine, which is more than 5 mg/100 g that is the allowable limit
      suggested by the U.S. Food and Drug Administration. Furthermore, 14 bacterial
      strains were isolated from sailfish fillets on a selective medium for histamine
      forming bacteria. These presumptive histamine-forming strains, such as Proteus,
      Enterobacter, Klebsiella, Rahnella, and Acinetobacter, have been identified and
      found to produce 20 to 2,000 ppm histamine after incubating at 37 degrees C for
      24 h.

PMID- 14968981
TI  - Visible contamination on animals and carcasses and the microbiological condition
      of meat.
AB  - It is generally assumed that preventing visible contamination of or removing
      visible contamination from carcasses will enhance the microbiological safety of
      meat. Visible contamination of carcasses can be reduced by washing or otherwise
      cleaning animals before slaughter, by dehairing hides before carcasses are
      skinned or dressed with the skin on, or by performing skinning and eviscerating
      operations in manners that avoid the transfer of filth from the hide to the meat
      or the spillage of gut contents. Visible contamination can be removed by washing,
      trimming, or vacuuming carcasses. The available data appear to indicate that, of
      the various actions that can be taken to obtain carcasses that are free of
      visible contamination, only minimizing the visible contamination of meat during
      skinning and eviscerating operations may also ensure a degree of control over the
      microbiological contamination of meat. It might be preferable for visible
      contamination to be controlled largely by superior skinning and eviscerating
      practices rather than by animal or carcass cleaning treatments, which may not
      prevent the depositing of bacteria on or the removal of substantial numbers of
      bacteria from carcasses.

PMID- 14968982
TI  - Perspectives. IOM panel demands universal coverage by 2010.

PMID- 14968983
TI  - [Clinical approach versus technology in medicine and allergy].

PMID- 14968984
TI  - [Increase in frequency of asthma in school children from Villahermosa, Tabasca,
      Mexico].
AB  - BACKGROUND: There is evidence that the worldwide prevalence of asthma is
      increasing, particularly in children. OBJECTIVE: To compare the cumulative
      prevalence of medical diagnosis of asthma among Mexican schoolchildren in two
      surveys 12 years apart. MATERIAL AND METHODS: The study populations of the two
      comparable cross sectional surveys comprise six to twelve years old public and
      private schoolchildren in Villahermosa, Tabasco, Mexico. Sample sizes in 1986 and
      1998 were 6,465 and 6,073 children and response rates were 72 and 85%,
      respectively. The sampling frame and sampling method were identical in both
      surveys. The prevalence of medical diagnosis was expressed by sex and age
      comparing 1986 to 1998. An analysis of contingency tables was used to asses the
      differences in the prevalence rates. RESULTS: Cumulative prevalence of medical
      diagnosis of asthma in 1986 and 1998 were 8.74 and 12.63%, respectively, 45% of
      increase. We found a significant increase in lifetime of asthma (p = 0.001). The
      observed increases were independent of sex and age. CONCLUSION: As it has come to
      pass all over, our results support a significant increase in the cumulative
      prevalence in the last 12 years among schoolchildren in Villahemosa, Tabasco,
      Mexico.

PMID- 14968985
TI  - [The asthmatic patient and his/her family dynamics].
AB  - BACKGROUND: Asthma is a chronic disorder of the airways that modify behavior
      response of persons and affect family function. OBJECTIVE: To determine if there
      is a disorder of the familial dynamics in asthmatic patients of Tamaulipas.
      MATERIAL AND METHODS: An observational, comparative, open and cross-sectional
      study was performed to determine: family categorization, family function and
      evaluation of conjugal subsystem. We included 300 persons who were 30 to 50 years
      old, male and female: 100 subjects with asthma diagnosis, 100 with diabetes type
      2 and 100 healthy people. RESULTS: The asthmatic subjects' age average was of
      45.67 years, complete nuclear family was documented in 15% of sick persons, women
      were the family head in 50% of the cases, we appreciated great family dysfunction
      in relation to: adaptability function (50%), participation (63%), family grow-up
      (61%) and feeling manifestations (64%). In 53% of the conjugal couple cases of
      the patients, do not carry out her family functions like: communication 59%,
      share out functions 59%, sexual satisfaction 60%, and making decision 59%.
      CONCLUSION: It is only feasible to treat these patients when there is an active
      participation of the family members.

PMID- 14968986
TI  - Sublingual immunotherapy.
AB  - Allergen-specific immunotherapy, together with drug therapy and allergen
      avoidance, is a cornerstone in the management of respiratory allergy in both
      adults and children. Since the introduction of sublingual administration of
      immunotherapy (SLIT), it was regarded as the most promising approach, especially
      because of its optimal safety profile. After 15 years of clinical trials, the WHO
      officially accepted SLIT as a routine clinical option in both adults and
      children. This paper reviews the up-to-date aspects about clinical efficacy,
      safety and pharmacokinetics of sublingual immunotherapy.

PMID- 14968987
TI  - [Non-surgical treatment in case of obstructive sleep apnea syndrome in children.
      Report of a case].
AB  - Consequences of obstructive sleep apnea syndrome in children include reduced
      performance during day, behaviour problems, diurmal hypersomnia, psychomotor
      development delay, severe forms of cor pulmonale, systemic hypertension, growing
      delay and death. This paper describes the clinical case of a 3-year-old girl with
      perennial symptoms of nasal obstruction characterized by nocturnal snoring, oral
      breathing, nasal voice, sleep apnea, nasal pruritus and rhinorrhea. Her treatment
      is also described.

PMID- 14968988
TI  - [Demodicidosis in a female patient treated as allergic blepharoconjunctivitis. A
      case report].
AB  - A 65-year old woman suffered from therapy resistant chronic
      blepharoconjunctivitis and rosacea, without improvement under therapy of systemic
      and topic antibiotics and topic steroids and antihistamines. Demodex folliculorum
      was found adhered to the hair bulb on microscopic examination. She received oral
      ivermectin with good response. Two months later demodicidosis recurred. Then she
      was treated with a combination of ivermectin and transfer factor with total
      remission. Demodex folliculorum considered as saprophytic mite may play a
      pathogenic role in ocular diseases.

PMID- 14968989
TI  - [Chronic granulomatous disease. Report of a case and review of the literature].
AB  - Chronic granulomatous disease is a little common primary immunodeficiency
      affecting innate immune system. This article presents the case of an 8-year-old
      female patient whose disease started at three months of age with respiratory
      ways' infections. When she was two years old, she suffered another presentation
      of right basal pneumonia and right cervical mass, whose biopsy reported childhood
      chronic granulomatous disease. At eight years old, patient suffered bacteraemia
      due to Salmonella group D, thus patient started prophylaxis with trimethoprim
      sulfamethoxazole and, to date, she has continued stable.

PMID- 14968990
TI  - Response to Uyanik's TMD series.

PMID- 14968991
TI  - Change in testing procedures leads to increase in new CDTs.

PMID- 14968992
TI  - Spleen cell research could yield potential cure for type 1 diabetes.

PMID- 14968993
TI  - Thumbs-up for sugarless chewing gum.

PMID- 14968994
TI  - Diabetes and the future.

PMID- 14968995
TI  - The benefits of resealing composite restorations.

PMID- 14968996
TI  - Ulcer management. "I just want it to be gone!".

PMID- 14968997
TI  - Aesthetics and function in anterior restorations. A practical approach.

PMID- 14968998
TI  - Noninvasive "face-lifts" for your dentate patients. A new technique.

PMID- 14968999
TI  - The indirect composite resin restoration. An underutilized restorative choice?

PMID- 14969000
TI  - Combating the adverse effects of bruxism in one visit.

PMID- 14969001
TI  - The suction cup denture. A century-old technology reborn.

PMID- 14969002
TI  - Endodontics from access to success, Part 1. Access, the important first step.

PMID- 14969003
TI  - Cosmetic rehabilitation of the young patient.

PMID- 14969004
TI  - Predictable restoration of Class 2 preparations with composite resin.

PMID- 14969005
TI  - Immunity and immunizations.

PMID- 14969006
TI  - Fabrication of a surgical implant template with guide tubes.

PMID- 14969007
TI  - How to build your dream practice, Part 3. Some remaining steps.

PMID- 14969008
TI  - Viruses, trojans, and worms ... oh my!

PMID- 14969010
TI  - Managing risk with patient restraints.

PMID- 14969011
TI  - Environmental health and nursing.

PMID- 14969012
TI  - Haven of hope.

PMID- 14969013
TI  - Staff perceptions of e-learning.

PMID- 14969014
TI  - A voice for the future. Interview by Barbara Sibbald.

PMID- 14969015
TI  - Nursing education as a respected area of research.

PMID- 14969016
TI  - Predictors of success in nursing education.
AB  - This correlational study was designed to determine if successful completion of
      the associate degree nursing program and success on the NCLEX-RN were correlated
      to scores on the Educational Resources, Inc. NET and Pre-RN Examinations. Data
      were collected from the educational records of the sixty-eight successful
      graduates from the fall 2001 class. This study found composite scores on the NET
      and Pre-RN were statistically significant, and were useful in predicting success
      on the NCLEX-RN. Consistent with the literature, this study found standardized
      measures and educational records may be useful screening tools for admission to
      nursing school, to predict success in the nursing program, and the NCLEX-RN.
      Faculty may utilize these findings in advising students, for developing support
      services and to assist students in developing an action plan to prepare for the
      NCLEX-RN. As suggested by sample size and correlations, a replication study was
      designed.

PMID- 14969017
TI  - Encouraging alternative forms of self expression in the generation Y student: a
      strategy for effective learning in the classroom.
AB  - A majority of students in the classrooms of colleges and universities today, are
      a product of a generation of latch key kids in which daycare, babysitters,
      television, and computers serve as surrogate parents. With the proliferation of
      technology, the internet, beepers and cell phones have become social lifelines
      for this generation. They are technology savvy, independent and resourceful.
      Conditioned to expect immediate gratification, these youth have shorter attention
      spans and also a low threshold for boredom. It can be quite a challenge for
      educators to keep these young people engaged in the classroom. This paper
      presents an innovative teaching/learning strategy used in a nursing school in
      Florida that accommodates the unique characteristics of these learners.

PMID- 14969018
TI  - A survey of how a region's A&E units manage pretibial lacerations.

PMID- 14969019
TI  - JWC/MoInlycke Scholarship: the winner's achievements one year on.

PMID- 14969020
TI  - Open surgical wounds: how does Aquacel compare with wet-to-dry gauze?
AB  - OBJECTIVE: To compare the healing rates of a hydrofibre dressing (Aquacel) and
      normal wet-to-dry gauze in the treatment of open surgical wounds. METHOD: Fifty
      patients with open surgical wounds were randomized to receive either saline
      moistened gauze or Aquacel. The rate of wound healing was measured as ml/day
      (deep wounds) or cm2/day (superficial wounds) at each dressing change until an
      investigator blinded to the patient group diagnosed the wounds as having healed
      or the patient was withdrawn from the study. RESULTS: Of the 50 patients, seven
      were withdrawn from the study after the first evaluation. Of the remaining 43
      patients, 21 had been randomly allocated to the gauze group and 22 to the Aquacel
      group. For deep wounds, a mean change in the wound healing rate of 1.9 +/- 1.3
      cm3/day was reported for the gauze group and 2.9 +/- 2.3 cm3/day for the Aquacel
      group. These results approach statistical significance (p = 0.082). For
      superficial wounds, the mean change in the healing rate was 1.6 +/- 1.5 cm2/day
      for the gauze group and 1.9 +/- 2.2 cm2/day for the Aquacel group, but this was
      not statistically significant. CONCLUSION: Aquacel appears to be at least as
      effective as wet-to-dry gauze in the healing of open surgical wounds.

PMID- 14969021
TI  - Reliability and validity of DESIGN, a tool that classifies pressure ulcer
      severity and monitors healing.
AB  - OBJECTIVE: This study reviews the validity and reliability of DESIGN, a tool for
      classifying pressure ulcer severity and monitoring progression towards healing.
      Only the tool's healing progression component was evaluated. METHOD: Inter-rater
      reliability was evaluated by calculating the agreement rate of scores, based on
      eight photos of pressure ulcers and six actual ulcers, made by a panel of seven
      nurses. Validity was assessed, using the same eight photos, by comparing DESIGN
      scores with those made using the validated Pressure Sore Status Tool (PSST).
      RESULTS: The DESIGN inter-rater reliability results showed a high correlation of
      r = 0.98 for the photos and r = 0.91 for the real-life patients with pressure
      ulcers, respectively, for all seven raters based on total scores. For validity, a
      correlation greater than 0.91 was found between the DESIGN and PSST scores.
      CONCLUSION: Based on our results, DESIGN was found to have both high inter-rater
      reliability and high validity among the seven nurses who quantitatively evaluated
      the wound-healing progress of the pressure ulcers in this study.

PMID- 14969022
TI  - Pregnancy and leg ulceration.

PMID- 14969023
TI  - A randomised controlled study of four-layer compression versus Unna's Boot for
      venous ulcers.
AB  - OBJECTIVE: This study set out to compare healing rates, handling properties and
      patient comfort of a four-layer bandage system (Profore) and Unna's Boot in the
      treatment of venous leg ulcers. METHOD: This was a prospective randomised
      parallel-group trial. Patients with venous leg ulcers from four centres in Italy
      were randomised to receive treatment with either Unna's Boot or Profore. Time to
      healing was recorded for a maximum of 24 weeks. Pain was assessed using a visual
      analogue scale. Staff assessed ease of application, while patients rated comfort.
      RESULTS: Data were available for 68 patients with 68 wounds. At 24 weeks complete
      healing was seen in 74% of the Profore group compared with 66% of the Unna's Boot
      group. The median time spent in the study was 50 days (range: 7-175 days),
      corresponding to 51 days (range: 7-175 days) for Profore patients and 49 days
      (range: 7-168 days) for Unna's Boot patients. There was no difference (p = 0.13)
      between the groups in time to closure. Overall, more Profore than Unna's Boot
      applications were rated as excellent. There was a significant difference, in
      favour of Profore, in ease of application at the final application (p = 0.013).
      At the initial application, there was a significant difference in bandage
      appearance (p = 0.04), again favouring Profore, but this was not sustained at the
      final application (p = 0.18). CONCLUSION: Profore is as effective as Unna's Boot
      in the treatment of venous leg ulcers.

PMID- 14969024
TI  - Patients' perceptions and experiences of larval therapy.
AB  - OBJECTIVE: To gain an insight into patients' perceptions and experiences of
      larval therapy. METHOD: A phenomenological approach was adopted in which six
      patients who recently had had larval therapy were interviewed using an open,
      unstructured approach in two hospital settings. Data analysis was loosely based
      on Colaizzi's structured analysis technique. RESULTS: Five themes emerged: past
      experiences of wounds leads to expectations of recurrence and a reduced quality
      of life; living with a chronic wound led to feelings of hopelessness; the skills
      and expertise of the nurse made patients feel hopeful; being informed helped
      patients to choose whether or not to have the therapy; the experience of larval
      therapy was not as scary as imagined. CONCLUSION: The findings suggest that,
      although initially repellent, larval therapy is acceptable once treatment starts.
      The nurse-patient relationship was a significant factor in acceptance, along with
      autonomy and informed choice.

PMID- 14969025
TI  - Are honey and sugar paste alternatives to topical antiseptics?

PMID- 14969026
TI  - Can debridement and the 'Belfast sandwich' avoid Ray amputation?

PMID- 14969027
TI  - Can laboratory investigations help us to decide when to discontinue larval
      therapy?
AB  - OBJECTIVE: This study investigated retrospectively whether three laboratory
      investigations--testing for leucocyte levels, C-reactive protein (CRP) and
      erythrocyte sedimentation rate (ESR)--can be used to guide the decision of when
      to discontinue larval therapy. METHOD: Between 1999 and 2002 we administered
      larval therapy to 16 inpatients. In all cases the decision to discontinue therapy
      was a clinical one made by the surgeon who headed the trauma department. We
      retrospectively analysed laboratory investigations, testing for leucocyte levels,
      CRP and ESR, on the first and last days of therapy to ascertain if the results
      could have guided this decision. RESULTS: The median leucocyte count on the first
      day of larval therapy was 10.5 (x 10e9/L) compared with 8.4 (x 10e9/L) on the
      last day (Friedman test: p < 0.05). CRP and ESR showed a non-significant tendency
      towards lower values. CONCLUSION: Although the methodological limitations of this
      open-label non-comparative cohort study preclude a definite conclusion, we
      believe that laboratory investigations, particularly leucocyte count, can guide
      the decision of when to discontinue larval therapy. However, this objective
      parameter cannot replace clinical judgement.

PMID- 14969028
TI  - Use of Promogran to treat venous leg ulcers.

PMID- 14969029
TI  - Normal birth: a public health issue.

PMID- 14969030
TI  - Midwives hurt by hygiene accusation.

PMID- 14969031
TI  - Poverty, pregnancy and childbirth.

PMID- 14969032
TI  - Sure start: what next?

PMID- 14969033
TI  - Perceptions of the Breastfeeding Best Start project.

PMID- 14969034
TI  - Body wisdom: detecting birth by smell.

PMID- 14969035
TI  - Midwifery basics: care during labour. The first stage of labour.

PMID- 14969036
TI  - Time for an independent voice.

PMID- 14969037
TI  - Assess the quality of your core measure data: what you find may be surprising.

PMID- 14969038
TI  - Program helps patients who take anticoagulants.

PMID- 14969039
TI  - Applying the principles of process variation.

PMID- 14969040
TI  - Involve key players to address infection control.

PMID- 14969041
TI  - Identifying protective alternatives for sharps-safety and needlestick-prevention
      devices.

PMID- 14969042
TI  - Designing healthcare facilities for patient safety.

PMID- 14969043
TI  - Early arthritis. Introduction.

PMID- 14969044
TI  - A historical perspective concerning population-based and clinical studies of
      early arthritis and early rheumatoid arthritis.
AB  - Research concerning early arthritis and early rheumatoid arthritis (RA) may be
      considered to have begun with population-based studies in the United Kingdom, the
      United States and Scandinavia, from the late 1950s to the late 1960s. These
      studies indicated that the majority of people with clinical findings of RA had no
      evidence of disease 3-5 years later, and that only about 25% to 30% of people in
      a population who met the criteria for RA had rheumatoid factor. These findings
      may have contributed to an underestimation of RA until the severity of long-term
      outcomes of clinical RA were recognized in the 1980s on the basis of clinical
      cohorts. The first major early RA clinical cohort was established in 1957-1963 in
      Bath, England. Although results at 3 and even 11 years were not overly
      unfavorable, by 15 and 20 years most patients had severe outcomes of functional
      declines and premature mortality. The Middle-sex (UK) early RA cohort established
      in 1966-1971 indicated that radiographic abnormalities were observed in about 70%
      of patients by 2 years of disease, and were seen in most patients initially in
      the feet. The Memphis (Tennessee, USA) early RA cohort established in 1967-1971
      suggested that a progressive course of RA is predicted by a higher number of
      involved joints at baseline. The Lund (Sweden) early RA cohort established in
      1985-1989 indicated rather severe long-term outcomes in patients treated
      according to traditional conservative approaches to use of disease modifying anti
      rheumatic drugs (DMARDs). The early RA study (ERAS) involving nine National
      Health Service trusts in the UK was established in 1987-93, and showed
      associations of education level and socioeconomic status with clinical status.
      The movement towards early arthritis clinics was given great impetus following
      the work by Emery in the early 1990s. These studies and others described
      elsewhere in this supplement have contributed to the foundations for the clinical
      approach to early arthritis in the 21st century.

PMID- 14969045
TI  - Diagnosing early rheumatoid arthritis (RA). What are the problems and
      opportunities?
AB  - Early diagnosis is being appropriately emphasized in RA, as early DMARD treatment
      can be very effective. ACR criteria are useful but may not perform as well in
      early disease. These criteria depend on clinical examination, which is subject to
      over- and under-interpretation. Ultrasound and MRI may offer advantages.
      Laboratory tests and synovial fluid analyses may contribute, but are often not
      definitive. All of these data, synovial biopsies and a variety of other features
      can guide prognosis as well as diagnosis. Consideration of the whole patient,
      including education levels and coping strategies, can help. Aggressive management
      is proposed for most patients once the diagnosis is firm. Strategies are needed
      to arrange that patients are seen at a very early stage by rheumatologists
      knowledgeable in the treatment of early arthritis. Early diagnosis is receiving
      increasing emphasis in RA, with the recognition that erosive irreversible disease
      can occur in the first months and that a variety of treatments can clearly
      prevent or slow disease progression (1, 2). Most studies addressing early RA use
      the American Rheumatism Association (ARA), now the American College of
      Rheumatology (ACR), criteria (3) for purposes of uniformity although these
      criteria have been shown to be less valid in early disease (4). Early DMARD
      treatment can make a difference, but there are a number of unanswered or
      partially answered questions about diagnosis that remain to be addressed. We
      review this area, focusing on work from our own research and how this has guided
      our thinking.

PMID- 14969046
TI  - Joint damage and disability in rheumatoid arthritis: an updated systematic
      review.
AB  - Joint damage and disability in rheumatoid arthritis (RA) both increase with
      disease duration but the nature of their relationship is uncertain. This review
      updates knowledge of the progression and inter-relationship of joint damage and
      disability in treated RA and provides a synopsis of the main predictive factors
      for damage and disability. In early RA 39-73% of patients develop one or more
      erosions in their hands and wrists by 5 years. In established RA the average
      annual increase in radiological damage scores is 1.9% maximal damage. After 20
      years RA patients have on average 43% of maximum possible damage. These data
      suggests that joint damage progresses constantly over the first 20 years of RA.
      The average annual increase in HAQ scores is 0.033 per year (1% of possible
      maximum disability). In the first years of disease there is a "J-shaped" curve
      with an initial fall in HAQ scores followed by an increase over the next four
      years. In cross-sectional studies there is either no correlation or a weak
      correlation between damage and disability in early RA; this absence of
      correlation is explained by the "J-shaped" curve of disability with disease
      duration in early RA. As disease duration increases the correlation between
      damage and disability becomes more obvious; 9 studies show correlation
      coefficients between 0.31 and 0.75. The most predictive factors of damage and
      disability are rheumatoid factor status and disease activity. The validity of our
      conclusions are limited by the potential indirect link between small joint damage
      and disability, with large joint damage being a more important predictor, and the
      presence of ceiling effects on X-rays. In conclusion, joint damage accounts for a
      substantial proportion of the disability associated with the disease.

PMID- 14969047
TI  - The histopathology of early synovitis.
AB  - Early diagnosis and therapeutic intervention are needed to prevent the morbidity
      related to erosive arthropathies such as rheumatoid arthritis (RA), yet it is
      difficult to distinguish various forms of synovitis early in the disease course.
      The availability of synovial tissue biopsy techniques has facilitated the
      analysis of synovial tissue from patients with early disease. Comparison of the
      histopathologic features of synovial tissue in early RA, established RA, and in
      non-RA synovitis has shown subtle, but potentially important differences in
      histologic features, cytokine and protease expression patterns, and apoptosis.
      Ultimately, it remains to be shown definitively that analysis of the
      histopathological features of synovial tissue early in disease is of independent
      value in identifying patients destined to have persistent synovitis or erosive
      disease, and in turn, in allocating patients to specific therapeutic strategies.

PMID- 14969048
TI  - Is radiographic progression a realistic outcome measure in clinical trials with
      early inflammatory arthritis?
AB  - Radiographic progression is one of the most important outcome measures in
      rheumatoid arthritis (RA) clinical trials, because it reflects historic disease
      activity, is associated with loss of function over time, and can be reliably
      assessed. Trials involving patients with early inflammatory arthritis (EIA) will
      differ from those focusing on RA patients in many respects. They include a
      heterogeneous spectrum of patients, and some of them will have self-limiting
      arthritis, or arthritis with a low likelihood of ever becoming erosive.
      Furthermore, because of the early presentation a high proportion of patients with
      a high likelihood of erosions will still be non-erosive at presentation; and
      since EIA trials will aim at permanent clinical remission induced by therapy, the
      signs of progression will be very subtle. Current radiographic scoring methods
      may not be sensitive to the small changes that are expected to occur in EIA
      trials. This makes radiographic progression a rather unlikely single primary
      outcome in such trials. However, "permanent clinical remission" (with or without
      therapy) appears to be a most realistic outcome in such trials, and radiographic
      stability (the demonstration of "no progression") may serve as a key criterion in
      establishing whether the endpoint of permanent clinical remission is actually
      met. The moment at which the first erosion develops is also important in making
      the correct diagnosis and has implications for the prognosis. We propose here a
      number of recommendations for the use of radiographic progression as one of the
      obligatory outcome measures in clinical trials with EIA.

PMID- 14969049
TI  - The role of ultrasonography and magnetic resonance imaging in early rheumatoid
      arthritis.
AB  - Advances in ultrasound (US) and magnetic resonance imaging (MRI) techniques have
      provided new methods for evaluating early rheumatoid arthritis (RA). Their
      diagnostic properties in terms of detecting primary pathology of RA (i.e.,
      erosions, bone changes, synovitis, tenosynovitis, and effusion) are reviewed.
      High-resolution US plays a significant role in therapeutic and diagnostic
      procedures. MRI also assists in the understanding of RA pathogenesis and joint
      mechanics.

PMID- 14969050
TI  - The evaluation of bone damage in rheumatoid arthritis with magnetic resonance
      imaging.
AB  - Magnetic resonance imaging (MRA) greatly improves the early detection and
      visualization of osseous and non-osseous joint changes over conventional x-rays
      of involved joints in patients with rheumatoid arthritis (RA). However, the
      "pathophysiological correlate" of these MR imaging changes remains poorly
      defined. Careful validation of MRI findings and the evaluation of MRI as a tool
      to follow the effect of therapy remain to be performed before MRI may be used as
      a clinical tool to follow therapy or as a surrogate for evaluating osseous
      changes over time.

PMID- 14969051
TI  - Biochemical markers of joint tissue turnover in early rheumatoid arthritis.
AB  - The progression of rheumatoid arthritis (RA), a disease characterized by
      synovitis, cartilage degradation and bone erosion, is highly variable from
      patient to patient. New specific biological markers reflecting quantitative and
      dynamic changes in joint tissue turnover have been recently developed and include
      assays for type II collagen synthesis and degradation and synovitis. Increasing
      evidence from prospective studies in early RA indicate that some of these markers
      may be useful to predict the progression and identify patients at risk for rapid
      joint damage, before any damage is detected by radiography. Although studies on
      their value in assessing the efficacy of treatments are still limited,
      preliminary data in early RA suggest that biological markers will play an
      important role in the development and the early monitoring of disease modifying
      antirheumatic drugs with respect to future radiographic progression.

PMID- 14969052
TI  - Autoantibodies in early arthritis: advances in diagnosis and prognostication.
AB  - Several excellent reviews have recently been published on the significance of
      autoantibodies in rheumatoid arthritis (RA) (1-4). Here we: (i) review selected
      longitudinal studies examining the predictive utility of autoantibodies in early
      arthritis and early RA cohorts; (ii) assess the relevance of autoantibodies as an
      independent parameter for prediction and prognostication of RA; and (iii)
      describe the potential of multiplex autoantibody assays, including miniaturized,
      high-throughput microarray technology, to improve diagnosis and prognostication
      in recent-onset synovitis/early arthritis patients.

PMID- 14969053
TI  - Number of active joints, not diagnosis, is the primary determinant of function
      and performance in early synovitis.
AB  - OBJECTIVE: A substudy within a larger study of patients with inflammatory
      arthritis of less than one year, to analyze baseline measures or joint counts,
      laboratory values, patient questionnaires and ARA diagnostic criteria for
      rheumatoid arthritis, as predictors of one year performance and functional
      status. METHODS: 229 patients with synovitis of less than one year were enrolled
      and evaluated at baseline and one year. Measures included the number of swollen
      or tender joints [active joint counts]; biological indices of inflammation
      [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)]; and patient
      questionnaire measures of pain [Wisconsin Brief Pain Inventory], fatigue [multi
      dimensional assessment of fatigue], depression [Center for Epidemiologic Studies-
      Depression Scale], sleep [Sleep Quality Index], performance [Human Activity
      Profile], and function [Sickness Impact Profile ambulation subscale and Health
      Assessment Questionnaire]. Correlations between these measures were evaluated
      using the Spearman rank order correlation. Patients were classified according to
      whether they met ARA criteria for RA, had high (> 7) or low (< or = 7) numbers of
      affected joints; and high, intermediate, or low levels of performance; and were
      compared using the Kruskal-Wallis test. RESULTS: At baseline, an active joint
      count of > 7 versus < or = 7 was associated significantly with higher age,
      rheumatoid factor positivity, a diagnosis of rheumatoid arthritis versus
      spondyloarthropathy or undifferentiated arthritis, and receiving a disease
      modifying antirheumatic drug (DMARD), but not with sex, race, erythrocyte
      sedimentation rate (ESR) or C-reactive protein (CRP), or receiving prednisone.
      Furthermore, high baseline active joint counts were associated significantly with
      patient questionnaire scores for maximum activity, fatigue and depression, but
      differences were not significant for sleep, ambulation and pain scores. A
      comparison of patients who met or did not meet criteria for RA indicated
      significant differences only according to the fatigue scores, but none of the
      other questionnaire measures. Correlations of baseline measures with one-year
      performance were highest for the baseline active joint count compared to
      laboratory and questionnaire variables. The maximum activity score at one year
      was predicted significantly by the baseline maximum activity score, active joint
      count, and age, but not by laboratory tests or whether the patient met criteria
      for RA. CONCLUSION: The active joint count predicts subsequent performance and
      function for patients with recent onset, inflammatory synovitis more effectively
      than whether patients met ARA criteria for RA.

PMID- 14969054
TI  - Work disability in early rheumatoid arthritis.
AB  - Patients with rheumatoid arthritis (RA) are at risk of work disability from the
      very start of their symptoms. Prospective cohorts including patients with early
      RA show that 20-30% become permanently work disabled during the first 2-3 years
      of the disease. Risk factors for early work disability include a physically
      demanding job, older age, and lower educational level, as well as the level of
      functional disability in daily activities. Work disability accounts for a major
      fraction of the costs of RA both to the patient and to society. Improved work
      disability outcomes in RA may require attention to social, economic, and
      political issues, and broader physician and public education concerning RA, in
      addition to improved medical management of the disease.

PMID- 14969055
TI  - Early arthritis clinic: a USA perspective.
AB  - An early arthritis clinic (EAC) was established to identify early rheumatoid
      arthritis (RA) patients for clinical trials and to create a facile method of
      early patient referral from the practitioner to the rheumatologist. With minimal
      advertising and promotion, patients with less than 12 months of symptoms were
      easily referred if the primary care physician suspected a rheumatic condition. Of
      those patients who were appropriately referred one-third had synovitis, 20% had
      diagnostic cutaneous findings, 20% were diagnosed with lupus (or lupus-like
      disease), 12.5% had RA, and 10% were diagnosed with a spondyloarthropathy. An EAC
      was easily established, implemented and staffed and resulted in the prompt
      diagnosis and early treatment of many patients who may have otherwise waited
      months for appropriate rheumatologic diagnosis and treatment.

PMID- 14969056
TI  - Uniform databases in early arthritis: specific measures to complement
      classification criteria and indices of clinical change.
AB  - Rheumatoid arthritis (RA) is not characterized by a single pathognomonic measure
      such as blood pressure in hypertension or cholesterol in hyperlipidemia, which
      can be used in the diagnosis, prognosis, and monitoring of patient status.
      Measures such as swollen joints and an elevated erythrocyte sedimentation rate
      are certainly valuable, but many individuals with abnormal values have conditions
      other than RA, and many people with RA may have favorable values for one or more
      of these measures. Therefore, the rheumatology community has developed indices of
      several measures, such as classification criteria, the disease activity score
      (DAS), and the ACR Core Data Set with 20%, 50% and 70% improvement (ACR 20, ACR
      50, ACR 70) to classify and monitor patients with RA. While these indices have
      greatly advanced clinical research, databases for long-term observations,
      including those in early RA described in this Supplement, differ in 20-50% of
      included data, and the software platforms for these databases differ sufficiently
      to render it difficult to merge the data to compare one data set to another. It
      has been proposed that a uniform database for early arthritis clinical research
      could help advance clinical research in early arthritis. One example of such a
      database, termed a "standard protocol to evaluate rheumatoid arthritis" (SPERA),
      has been in use for almost two decades in one clinical site, and has proven
      valuable in a number of ways, including the demonstration of early radiographic
      damage, development of a 28-joint count, and documentation that patient
      questionnaire data are correlated significantly with laboratory, joint count and
      radiographic data, although questionnaire data are the strongest predictors of
      severe outcomes including work disability and premature mortality. The use of a
      uniform database in no way precludes the collection of additional data at
      particular centers including immunogenetic, serologic, or structural magnetic
      resonance imaging (MRI) data. However, the availability of an infrastructure of
      standard data in all RA databases would enhance clinical research in early RA.

PMID- 14969057
TI  - Early predictors of outcome in juvenile idiopathic arthritis.
AB  - The definition and management of "early arthritis" in children differ from those
      in adults because juvenile idiopathic arthritis (JIA) is markedly different from
      adult rheumatoid arthritis. Since a significant proportion of patients with JIA
      develop articular damage and enter adult life with persistently active disease,
      it is important to predict early in the disease course the long-term outcome in
      order to tailor treatment to the risk of disability. Over the past 3 decades a
      number of studies have evaluated the long-term outcome of cohorts of patients
      with JIA and some of them have also attempted to identify early prognostic
      factors. In summary, greater severity/extension of arthritis at onset, symmetric
      disease, precocious hip/wrist involvement, the presence of rheumatoid factor, and
      prolonged active disease were the best predictors of a poor outcome. Specific
      correlates for systemic JIA were persistent systemic features and thrombocytosis
      at 6 months following presentation, whereas joint symmetry and a higher
      erythrocyte sedimentation rate at onset were associated with a more severe course
      in oligoarticular JIA. However, although data is accumulating on prognostic
      factors in JIA, prediction of long-term outcome in the first few months remains
      difficult. To better define prognostic factors in future analyses, a considerable
      effort should be made to increase standardization among studies. Furthermore, a
      radiographic scoring system and a set of remission criteria specific for JIA
      should be developed.

PMID- 14969058
TI  - The Norfolk Arthritis Register (NOAR).
AB  - The Norfolk Arthritis Register (NOAR) has been recruiting and following patients
      with early inflammatory polyarthritis (IP) since 1989. Approximately three
      quarters of the patients followed satisfy classification criteria for rheumatoid
      arthritis (RA) by 5 years from symptom onset. This paper summarises the
      publications which have been based on the NOAR cohort with respect to the
      incidence and prevalence of IP and RA, genetic and environmental risk factors for
      the development of IP, outcome following the development of IP and predictors of
      outcome. It also discusses methodological issues in examining the treatment
      effect in observational cohorts and the costs to the healthcare system of
      patients with early IP.

PMID- 14969059
TI  - The Leiden Early Arthritis Clinic.
AB  - In 1993 a special Early Arthritis Clinic (EAC) was established at the Department
      of Rheumatology of the Leiden University Medical Center in order to detect and
      treat inflammatory disorders early in the disease state, especially early
      rheumatoid arthritis. Patients with confirmed arthritis of recent onset (less
      than 2 years) were included by rheumatologists and trained research nurses.
      Parameters of first and follow-up visits (3, 6 and 9 months and yearly) that were
      entered in the EAC-database include the medical history, physical-diagnostic
      examination, laboratory tests, questionnaires, radiographic joint scores and
      diagnosis. This database enables us to conduct research on arthritis, with an
      emphasis on rheumatoid arthritis, in many ways. Physicians and basic scientists
      have studied cellular immunology and genetic, environmental and clinical risk
      factors in order to determine the pathophysiologic mechanisms of inflammatory
      arthritis. The present article is a review on reports published from the EAC.
      Over the past ten years, these reports have been highly relevant for both daily
      clinical practice and research. Present and planned future studies, as described
      in this article, reconfirm the importance of an EAC framework to ensure that
      research continues on this disease in the Leiden EAC area.

PMID- 14969060
TI  - Early arthritis and rheumatoid arthritis in Germany.
AB  - Early arthritis is challenging because the clinical picture often does not allow
      a distinction between rheumatoid arthritis (RA), self-limiting disease, and other
      forms of inflammatory arthritis. In Germany the first early synovitis clinic and
      several inception cohorts of patients with early RA were initiated and evaluated
      during the 1980s and 1990s to learn more about diagnostic classification, psycho
      social problems and socio-economical status including sick-leave, work loss, and
      indirect costs of patients with early arthritis and early RA. Unclassified
      arthritis was described as the most frequent diagnosis and the term
      "undifferentiated arthritis" was chosen to underline the heterogeneity of theses
      arthritides and the preliminary state of this classification as a working
      diagnosis. A large National Databank of the German Regional Collaborative
      Arthritis Centres has been established over the last 10 years. In total, there
      are some 170,000 cases in the database. Moreover, a prospective multicentre
      inception cohort of early RA of less than 1 year's disease duration has been
      started recently to evaluate parameters of potential relevance for the
      pathogenesis of RA and eventually for the prediction of erosive disease. Studies
      are in progress to test the diagnostic performance of specific antibodies and
      antibody patterns for RA. Another topic of research addresses the identification
      of bacterial DNA in synovial fluid and synovial tissues to improve the
      differentiation of patients with reactive arthritis from those with early RA and
      to narrow the working diagnosis of undifferentiated arthritis.

PMID- 14969061
TI  - The Austrian Early Arthritis Registry.
AB  - The Austrian Early Arthritis Registry (Austrian Early Arthritis Action, EAA)
      enrols and follows patients with inflammatory arthritis of very short (< 12
      weeks) duration. Currently, data on 375 patients (almost 2000 individual follow
      up examinations) have been entered into the EA database. Evaluations of data from
      182 patients with a follow-up of at least one year are available. 65% of these
      patients have RA, as diagnosed using the ACR classification criteria in a
      cumulative fashion. Approximately 15% of these patients still have no established
      diagnosis and are being carried forward and observed as cases of
      "undifferentiated arthritis". In RA patients, the mean DAS 28 decreased
      significantly from an initial mean score of 5.5 (high disease activity) into the
      range of low disease activity. At the end of one year a DAS 28 of < 3.2 was
      observed in 52% of the RA patients. Radiological progression in these RA
      patients, who also received treatment very early, appears to be less severe than
      in other cohorts, although direct comparisons are impossible due to different
      methods of patient selection. In addition, the serological data from our cohort
      in cooperation with other study groups will allow development and validation of
      possible prediction algorithms for early arthritis patients which could improve
      the diagnostic and therapeutic approach to this patient group.

PMID- 14969062
TI  - The Oslo experience with arthritis registries.
AB  - The Oslo experience with early rheumatoid arthritis (RA) is based on studies
      performed within the setting of a register of RA patients and of the longitudinal
      follow-up of patients with early RA. This article discusses some relevant issues
      for research on early arthritis: whether the current RA classification criteria
      are appropriate, the shift in incidence toward elderly patients, and the
      heterogeneity of the disease. Our data clearly show that 3 of the items of the
      classification criteria are infrequently fulfilled early in the disease and that
      RA most frequently starts after the age of 60. Our data also suggest that disease
      onset may be defined either as symptom onset or as when the classification
      criteria are fulfilled. The choice between these 2 options does not seem to
      influence the longitudinal results.

PMID- 14969063
TI  - The French early arthritis registry.
AB  - This report is focused on two French multicenter cohorts of patients with early
      rheumatoid arthritis (RA). The first one is a community-based study which was
      started in 1993. It was mainly designed to identify prognostic factors of joint
      destruction, disability and remission in patients with early RA. The 3-year and 5
      year results have been recently reported. Briefly, progression of joint damage
      was best predicted at baseline by radiographic scores, ESR, CRP, rheumatoid
      factor and DRB1*04 genes, and disability by disease activity including the HAQ
      score. Recently, the French Society of Rheumatology initiated a large national
      multicenter registry (800 patients), the "ESPOIR cohort study", that could serve
      as a database to allow investigations not only on diagnostic and prognostic
      markers, but also on etiologic, pathogenic and medico-economic factors among
      patients with early inflammatory arthritis who could later develop RA. The
      objectives, design and organization of this early arthritis registry are
      described.

PMID- 14969064
TI  - Aggressive rheumatoid arthritis registry in Italy. Characteristics of the early
      rheumatoid arthritis subtype among patients classified according to the ACR
      criteria.
AB  - The Italian Society of Rheumatology in the year 2000 decided to sponsor the
      creation of a data base (Registry) of consecutive patients who fulfilled the
      diagnosis of rheumatoid arthritis (RA) according to the American College of
      Rheumatology (ACR) criteria. The registry is designed to collect data on the
      "aggressive" type of RA all over the country in order to determine the percentage
      of patients who satisfy the established criteria among incident cases of RA and
      to define the therapeutic approach according to the characteristics of the
      enrolled patients. Predefined criteria set up by eight recognized opinion leaders
      on the disease were used by all the centers to create the database. The GIARA
      registry (Gruppo Italiano Artrite Reumatoide Aggressiva) has now enrolled 706
      patients who will be followed up for 24 months. They have been divided into two
      major subsets--patients with early (< 4 months' disease duration) and late (> 4
      months) RA--with the aim of establishing whether differences in clinical,
      serological, radiographic and therapeutic (DMARDs: disease modifying
      antirheumatic drugs) parameters may distinguish the two subsets. The major
      conclusion of this preliminary analysis is that an overall tendency to
      undertreatment is discernable.

PMID- 14969065
TI  - Early rheumatoid arthritis in Finland.
AB  - The first Finnish early rheumatoid arthritis (RA) cohort was established in 1973
      75 at the Rheumatism Foundation Hospital in Heinola, a hospital for rheumatic
      diseases only. Since then early RA cohorts for the purposes of longitudinal
      observation have been established at the Jyvaskyla Central Hospital and Helsinki
      University Hospital. Furthermore, 199 patients with early RA were enrolled in a
      multicenter randomized controlled study in 1993-95. The primary observations from
      these cohorts are summarized in this essay.

PMID- 14969066
TI  - Early rheumatoid arthritis in African-Americans: the CLEAR Registry.
AB  - African-Americans have been under-represented in genetic studies of rheumatoid
      arthritis (RA) susceptibility and severity. Genetic and non-genetic factors
      influencing the radiographic severity of RA and its response to treatment are
      poorly understood, particularly in African-Americans. The Consortium for the
      Longitudinal Evaluation of African-Americans with early RA (CLEAR) Registry, a
      collaborative effort among four institutions in the southeast USA, will hopefully
      provide a useful resource to study these issues.

PMID- 14969067
TI  - Databases of patients with early rheumatoid arthritis in the USA.
AB  - Several databases of patients with early rheumatoid arthritis (RA) have been
      established in the USA. The University of Tennessee at Memphis Cohort was
      organized in 1967-1971 to enroll 50 young adults (16-44 years) with symptom onset
      of < or = 6 months who met the 1958 American Rheumatism Association (ARA)
      criteria for at least probable RA. Two important observations from this database
      were that many patients seen within the first 6 months of meeting the criteria
      for probable RA have a self-limited rather than progressive disease, and that
      progressive disease is predicted by a high number of baseline swollen and tender
      joints. The National Institutes of Health (NIH) cohort of patients with
      peripheral synovitis for > or = 6 weeks but < 12 months in at least one
      peripheral joint was established in 1994. At the one-year follow-up, 45% of the
      patients met the RA criteria, 9% had reactive arthritis, 6% had psoriatic
      arthritis, 5% had other rheumatic diseases, and 35% had undifferentiated
      arthritis. The number of active joints, rather than meeting the criteria for RA,
      was the primary determinant of function and performance after one year. The
      Western Consortium of Practicing Rheumatologists (CPR) was established in 1993 to
      enroll patients with an RA duration < 1 year, positive rheumatoid factor, > or =
      6 swollen and > or = 9 tender joints, and no previous treatment with disease
      modifying anti-rheumatic drugs (DMARDs). Data from this cohort indicated the
      validity of self-report joint counts. American College of Rheumatology 20%
      improvement (ACR20) responses were seen in 50% of patients at 6 months and in 57%
      of patients at 24 months, while antinuclear antibodies (ANA) were seen in 69% of
      patients prior to the availability of biologic agents. The North American Cohort
      of Patients with Early RA (SONORA), which included patients with symptoms for > 3
      but < 12 months, indicated that methotrexate (MTX) was the most frequently
      prescribed DMARD, being taken by more than half the patients. The Consortium for
      the Longitudinal Evaluation of African-Americans with RA (CLEAR) registry and DNA
      repository has enrolled 123 African-American patients with early RA of less than
      2 years' duration to analyze genetic and non-genetic factors associated with
      disease severity. The Early RA Treatment Evaluation Registry (ERATER) of patients
      with early RA (< 3 years) was established in 2001. In this registry, MTX was the
      first DMARD used in 83% of patients, and most patients would not meet the
      criteria for inclusion in recent clinical trials of biological agents. Further
      observation of recent cohorts of patients with early RA over the next decade
      should be informative regarding whether aggressive intervention strategies and
      new DMARDs and biologic agents lead to improved long-term outcomes.

PMID- 14969068
TI  - Window of opportunity in early rheumatoid arthritis: possibility of altering the
      disease process with early intervention.
AB  - Therapeutic strategies for the treatment of rheumatoid arthritis (RA) have
      changed significantly in the last decade. The emphasis is now on early
      intervention with the aim of preventing disability and irreversible damage.
      Advocates of early intervention would suggest an alteration in the disease
      process, not just debulking of inflammatory disease. The data would at least
      support attenuation of the disease process with aggressive early therapy. Further
      research is required to elucidate the scientific mechanisms involved and their
      impact on the pathological progress of RA.

PMID- 14969069
TI  - Disease-modifying anti-rheumatic drug therapy and structural damage in early
      rheumatoid arthritis.
AB  - The appearance of measurable structural damage in rheumatoid arthritis (RA) is an
      indicator of disease severity and future disability. Disease-modifying anti
      rheumatic drugs (DMARDs) used in combination appear to be more effective than
      monotherapies at reducing the rate of progressive joint damage during randomized
      controlled trials. In clinical practice, however, combination DMARD therapy is
      still largely reserved for patients who have failed to respond to monotherapy.
      High dose corticosteroid, when given in early disease with combination DMARD
      therapy, may continue to ameliorate disease severity and progression for years
      after discontinuation of the high dose. To date, no DMARD combination has totally
      arrested joint damage in all patients with early RA. Future randomised controlled
      trials should always include prospective radiographic data as a primary outcome
      measure.

PMID- 14969070
TI  - The Utrecht experience with different treatment strategies in early rheumatoid
      arthritis.
AB  - Since 1990 the Utrecht Rheumatoid Arthritis Cohort study group has performed
      several clinical trials on different treatment strategies in early rheumatoid
      arthritis (RA) patients. From 1990 till 1994, patients were randomly assigned to
      the pyramid strategy group or the early DMARD group. Patients in the early DMARD
      group were allocated to one of the three following treatment strategies: strategy
      I, starting with hydroxychloroquine (HCQ); strategy II, starting with
      intramuscular gold (iAU); or strategy III, starting with oral methotrexate (MTX).
      After one year, statistically significant advantages for the early DMARD group
      compared with the pyramid group were found for disability, pain, joint score, and
      ESR. The increase in radiological damage did not differ significantly between the
      two strategy groups. These first year results proved that early introduction of
      DMARDs is more beneficial than a delayed introduction. After 5 years, however, no
      prolongation of the clinical advantages in favor of the early DMARD group, as
      observed after one year, was found. It was found that patients assigned to the
      pyramid group received more intra-articular injections during the first two
      years; at the end of this period 75% of them used DMARDs, especially the more
      aggressive DMARDs. Based on the first year results, all patients were randomly
      assigned to one of the three treatment strategies in the early DMARD group
      between 1994 and 1998. Patients who started with MTX or iAU as the first DMARD
      demonstrated better results regarding clinical efficacy and radiological damage
      after 2 years. However, more patients who received iAU therapy had to discontinue
      their therapy compared with patients who took MTX. We therefore conclude that MTX
      is the DMARD of first choice and that treatment should be tailored to the
      individual patient.

PMID- 14969071
TI  - DMARD use in early rheumatoid arthritis. Lessons from observations in patients
      with established disease.
AB  - The concept of early and aggressive therapy of rheumatoid arthritis (RA) has been
      well documented in the past years. It includes immediate DMARD institution after
      diagnosis, the use of the most effective DMARDs, and rapid switching of regimens
      if a level of disease activity close to remission is not achieved. In this review
      we briefly explore to what degree this new concept has been implemented in
      routine clinical care. Based on an observational dataset comprising 3342 DMARD
      courses, we present evidence of a change in DMARD patterns in newly diagnosed RA
      patients towards a higher prescription rate of more aggressive drugs like
      methotrexate (MTX), as well as a decreasing lag time until MTX was instituted in
      RA patients over the years. One consequence of recent changes in therapeutic
      strategies is that comparative analyses of formerly versus recently employed
      DMARDs will be considerably biased in observational studies. By contrast to
      changes in DMARD usage, survey data show neither a shortening of referral time
      nor a change in the approach to diagnose early RA. These data indicate a need for
      more dissemination of the early arthritis concept.

PMID- 14969072
TI  - Combination therapy in early rheumatoid arthritis.
AB  - The course of rheumatoid arthritis (RA) is determined early and the goals in
      early RA are to prevent radiologic joint degradation and to achieve optimal
      clinical and biological remission. Achieving these goals means that many RA
      patients may be candidates for combination disease-modifying therapy. We review
      data from randomized clinical trials regarding the impact of these treatment
      strategies as the initial therapy in early RA. It appears likely that the place
      of combination therapy will increase in the coming decades, even in very early RA
      patients, where the ultimate goal is persistent remission.

PMID- 14969073
TI  - Methotrexate as the "anchor drug" for the treatment of early rheumatoid
      arthritis.
AB  - The two major advances over the 1990s in the treatment of rheumatoid arthritis
      (RA) were a shift in strategy from a "pyramid", in which disease modifying anti
      rheumatic drugs (DMARDs) were deferred for several years, to the early aggressive
      use of DMARDs and widespread acceptance of methotrexate as the DMARD with the
      most long-term effectiveness and safety. Methotrexate courses are continued far
      longer than those of any other DMARD, an excellent indicator of greater
      effectiveness and safety. In one recent series, methotrexate was the first DMARD
      used in more than 80% of patients with RA. Studies which document the superiority
      of combinations of methotrexate with biological agents to methotrexate
      monotherapy select for only a minority of contemporary patients with RA who have
      severe disease activity and incomplete responses to methotrexate. In one locale,
      only 5% of patients met criteria for the Anti-Tumor Necrosis Factor Trial in RA
      with Concomitant Therapy (ATTRACT) trial and only 30% met the criteria for the
      Early Rheumatoid Arthritis (ERA) trial. In studies comparing methotrexate
      directly with biological agents, the biological agents have greater efficacy in
      patients with very severe disease, but the best results are seen in patients who
      take a combination of methotrexate and biologic agents. These data establish that
      methotrexate is the anchor drug and probably should be the first DMARD used in
      the majority of patients with RA at this time.

PMID- 14969074
TI  - Low dose glucocorticoids in early rheumatoid arthritis.
AB  - The use of glucocorticoid therapy in the treatment of rheumatoid arthritis [RA]
      remains controversial. There has been much data accumulated over the years
      describing both the risks and benefits of acute and chronic glucocorticoid
      therapy. Initially there was significant enthusiasm for this type of therapy
      given the extent of the anti-inflammatory effects. However, use was then modified
      as chronic therapy with higher doses was associated with frequent reports of
      important safety concerns. More recently low dose glucocorticoid therapy (e.g. <
      or = 5 mg prednisone per day) is being reconsidered in particular for patients
      with early disease. This paper will review the historical experience with higher
      dose therapy along with the evolving evidence of an improved benefit to risk
      ratio with the advent of concomitant therapies to minimize some of the more
      problematic adverse events associated with chronic use of even low dose
      glucocorticoid therapy. It is suggested that with appropriate monitoring and
      careful concomitant prophylactic therapy to prevent osteoporosis, adjunctive
      therapy using low dose glucocorticoids along with the appropriate disease
      modifying anti-rheumatic drug may be a reasonable treatment plan for select
      patients.

PMID- 14969075
TI  - Role of biologics in early arthritis.
AB  - Recent advances in the management and treatment of rheumatoid arthritis (RA) have
      provided evidence for the importance of early diagnosis and treatment of the
      disease. Biological therapy with monoclonal antibodies, including anti-tumor
      necrosis factor (TNF) agents have shown major efficacy in terms of disease
      activity and outcome of inflammatory arthritis in trials. Interest has focused on
      the treatment of early rheumatoid arthritis with anti-TNF agents to induce long
      term impact on outcome. A major study of etanercept versus methotrexate (MTX)
      showed some benefit at one year for the etanercept group, but long-term data have
      shown greater benefit. Two double-blind placebo-controlled studies of infliximab
      in patients with early RA yielded promising data, showing the possibility of a
      true 'window of opportunity' with long-term benefit from a short term treatment
      period. Aggressive treatment by anti-TNF agents as well as combination therapies
      of disease modifying anti-rheumatic drugs (DMARDs) in patients with very early
      disease would be a logical approach to be investigated in the future.

PMID- 14969076
TI  - The Early Rheumatoid Arthritis (ERA) trial comparing the efficacy and safety of
      etanercept and methotrexate.
AB  - The Early Rheumatoid Arthritis (ERA) trial compared monotherapy with etanercept
      or methotrexate in patients with early erosive rheumatoid arthritis. Over the
      initial period of 12, and subsequently 24, months both treatments were associated
      with a profound reduction in radiographic progression of joint damage, as well as
      a reduction in signs and symptoms of disease. Etanercept showed slight
      superiority to methotrexate in reducing subsequent radiographic erosions and in
      the rapidity of the clinical response. Both therapies proved to be safe and well
      tolerated and, importantly, the relative safety and tolerance of a rapidly
      escalated dosing regimen for methotrexate was demonstrated. In summary, early
      aggressive treatment of RA is associated with clinical and radiographic benefit
      that can be demonstrated after a relatively short period of treatment.

PMID- 14969077
TI  - Role of adalimumab in the treatment of early rheumatoid arthritis.
AB  - Adalimumab, a recent addition to the therapeutic armamentarium in rheumatoid
      arthritis (RA), has been evaluated in patients with early RA. The DE019 study, a
      double blind randomized placebo controlled trial of adalimumab given 20 mg once a
      week or 40 mg every other week demonstrated both clinical and radiographic
      efficacy. A subset analysis of patients with early disease revealed that early
      treatment with adalimumab may be more efficacious than therapy later in the
      course of disease, particularly with regard to radiographic progression. The
      findings support early aggressive intervention in RA.

PMID- 14969078
TI  - Role of infliximab in the treatment of early rheumatoid arthritis.
AB  - Data has been generated that infliximab may be more effective when initiated
      earlier in the course of disease. A subset analysis of the Attract trial has
      demonstrated better efficacy of infliximab in reducing joint damage in an early
      rheumatoid arthritis (RA) population. Recently a randomized double-blind
      controlled trial revealed that infliximab in combination with methotrexate (MTX)
      in an early RA population improved signs and symptoms as well as inhibition in
      radiographic progression compared with patients receiving infliximab or MTX
      alone. The possibility of withdrawing infliximab after induction of remission
      with a combination of infliximab and MTX has been shown in a small pilot trial.
      Taken together, the results support the early use of infliximab in the treatment
      of patients with moderate to severe disease.

PMID- 14969079
TI  - The safety of biologic agents in early rheumatoid arthritis.
AB  - Accompanying the excitement surrounding the prominent efficacy of biologic agents
      in rheumatoid arthritis (RA) has been concern regarding potential adverse
      effects. Data from clinical trials and pharmacovigilance has provided an
      assessment of their safety in patients with established RA. As biologic agents
      are utilized in patients with earlier disease, optimal determination of the
      risk/benefit will depend on continued careful monitoring, collection, reporting
      and analysis of safety information.

PMID- 14969080
TI  - A proposed treatment algorithm for rheumatoid arthritis: aggressive therapy,
      methotrexate, and quantitative measures.

PMID- 14969081
TI  - [Clinical analysis of pulmonary tuberculosis detected during follow-up of other
      underlying diseases].
AB  - OBJECTIVE: The objects of this study were to analyze clinically the outpatients
      and inpatients who were diagnosed as pulmonary tuberculosis during the follow-up
      of other underlying diseases at our affiliated hospitals and to review the past
      problems and to discuss how to improve the situation. METHODS: Sixty five
      outpatients or inpatients diagnosed as pulmonary tuberculosis during the follow
      up of other underlying diseases were collected from 508 patients with pulmonary
      tuberculosis at our affiliated hospitals over the past 10 years. RESULTS: The
      proportion of elderly patients over 65 years old among 65 index cases was
      significantly higher as compared to the control group. Forty three of these index
      patients were outpatients and 22 were inpatients. The most frequent underlying
      diseases excluding respiratory diseases were malignant diseases followed by
      diabetes mellitus, gastrointestinal diseases and psychosomatic diseases in order.
      Pulmonary tuberculosis without clinical symptoms was detected by periodic chest X
      ray in 21 cases (32%). There were some severe TB cases caused by the doctor's
      delay who were followed for malignant or psychosomatic diseases. CONCLUSION:
      Although many doctors except for respiratory specialists tended to pay attention
      to pulmonary tuberculosis as a possible complication during periodic health
      examination, further intensive education regarding pulmonary tuberculosis is
      required for doctors who treat malignant or psychosomatic diseases at special
      hospitals because TB patients who were smear positive when they were detected may
      cause outbreak of tuberculosis in the hospital.

PMID- 14969082
TI  - [The usefulness of lymphocyte stimulation test (LST) in side effects of
      antituberculosis drugs].
AB  - PURPOSE: The usefulness of the lymphocyte stimulation test (LST) was examined in
      patients who arose side effects to antituberculosis drugs. METHODS: The
      usefulness of LST was examined in 36 patients from January, 1999 to July, 2002.
      RESULTS: There were 11 LST positive patients, and the LST positive rate was
      30.6%. The causing agents determined by the LST positive patients were INH in 7,
      RFP in 3 and EB in one. The sensitivity of LST was 46.2% and the specificity of
      LST was 76.6%. CONCLUSION: LST positive rate of antituberculosis drugs was low
      and it was difficult to determine the causing drugs by LST.

PMID- 14969083
TI  - [A case of pulmonary tuberculosis complicated with tuberculosis of bilateral
      cervical lymph nodes and exacerbated pericostal abscess].
AB  - A 23-year-old man was admitted to our hospital because of cough and sputum in
      April 2001. A chest roentgenogram revealed infiltrative shadow with cavity
      formation in the bilateral lung fields. He was treated with sensitive
      antituberculous drugs. After starting the antituberculous therapy with INH, RFP,
      EB and PZA, bilateral cervical lymphadenopathy developed. Three months later,
      pericostal abscess appeared in the left anterior chest wall. Microscopic
      examination of the specimen obtained by needle aspiration biopsy disclosed
      positive for acid-fast bacilli. Smears of the pus showed acidfast bacilli
      identified as Mycobacterium tuberculosis by DNA-DNA PCR method. He developed
      tuberculous bilateral cervical lymphadenopathy and pericostal abscess during the
      course of antituberculosis chemotherapy. Drug sensitivity test revealed that
      tubercle bacilli in this case were sensitive. One year after the administration
      of chemotherapy, cervical lymphadenopathy and pericostal abscess were improved.
      Both masses were discontinuous with pulmonary tuberculosis and the possibility of
      lymphogenous spread of organism was speculated as its etiology. We assumed that
      both masses were due to paradoxical response to the antituberculosis
      chemotherapy.

PMID- 14969084
TI  - [Tuberculosis control in Kawasaki City--promoting the DOT program].
AB  - Kawasaki City initiated the DOT (Directly Observed Therapy) program in 2000 to
      improve tuberculosis (TB) control in the homeless persons and individuals living
      in temporary subsidized housing. The program was implemented as an additional
      program to the city's control policy of mass TB screenings for these groups. The
      DOT program was implemented through participation of numerous agencies sharing
      common goals. Through coordination and cooperation, a strategy suitable for the
      regional level was developed. Sectors involved were not only the TB control staff
      within the public health centers but also the entire public health centers, the
      welfare administrative division, the city's TB task force and homeless task
      force, and regional medical institutions. With the implementation of the DOT
      program, proper medical treatment, improved patient care, and various other
      measures were performed, and this led to the strengthening of TB control not only
      in designated DOT-implemented areas but also in the entire city. As a result, the
      treatment outcomes improved, and incidence rate of TB began to decrease.

PMID- 14969086
TI  - [Refractive errors and accommodation].

PMID- 14969085
TI  - [Diabetes and tuberculosis--bad companions].
AB  - Diabetes and tuberculosis are bad companions each other. In this clinical review
      article on diabetes, the pathophysiology of diabetes is documented from the
      viewpoint of both insulin secretory dynamics and insulin action on various target
      organs. The mechanisms why atherosclerosis is accelerated in diabetes is also
      mentioned. Nowadays, there are many modalities to correct the deranged glucose
      fluxes, thus it is not difficult to maintain near-normal glycemic excursions in
      diabetic patients. Strict glycemic regulation is obligatory if the patient with
      tuberculosis has diabetes.

PMID- 14969087
TI  - [The accommodative characteristics of gazing at stereoscopic images on a 3-D
      display].
AB  - PURPOSE: We measured the accommodative response in order to investigate the
      influence of a visual function when gazing at stereoscopic images presented on a
      three dimensional display. METHODS: Accommodative step responses were measured
      using an infrared optometer, setting the far target at the distance of 1 m and
      the near target at the distance of 50 cm. The step response of the right eye was
      examined 6 times at 10-second intervals. The far target was a starburst as a real
      image and the near target was a white circle on a random dot background on a
      parallax barrier system three-dimensional display as a stereoscopic image
      generated with a 90-min arc binocular crossed disparity(+1.5 degrees) and a 90
      min arc binocular uncrossed disparity (-1.5 degrees), and a 0-min disparity (0
      degree). The near target was presented in 4 ways: 1. -1.5 degrees disparity
      alone, 2. 0-min disparity alone, 3. +1.5 degrees disparity alone, and 4. +1.5
      degrees and -1.5 degrees disparity alternately. RESULTS: In conditions 1 to 3,
      the mean +/- standard deviation values of the accommodative response were 0.59 +/
      0.16 D, 0.72 +/- 0.11 D, and 1.03 +/- 0.21 D, respectively. The accommodative
      response was very large at the disparity of +1.5 degrees compared with the
      disparity of 0 degree (p = 0.0300). It was not significant although there was a
      tendency to become small at the disparity of -1.5 degrees (p = 0.0707). In
      condition 4, the mean +/- standard deviation values of the accommodative response
      were 0.62 +/- 0.12 D in the condition of -1.5 degrees and 1.03 +/- 0.26 D in
      condition +1.5 degrees with significant difference (p = 0.0122). CONCLUSIONS: The
      over accommodation response is induced when gazing at a stereoscopic image under
      the condition of binocular crossed disparity. This indicates that gazing at
      stereoscopic images has ill effects on the accommodative system.

PMID- 14969088
TI  - [The posterior portion of the eyeball and the muscle cone in cases of high
      myopia].
AB  - PURPOSE: To study the displacement of the eyeball of high myopia in the muscle
      cone. METHODS: Three patients with esotropia with high myopia(myopic esotropia
      group), seven patients with high myopia without esotropia (high myopia group),
      and eight controls(control group) were examined. Using magnetic resonance
      imaging, the outer axial length and the displacement of the posterior portion of
      the eyeball in the muscle cone were measured. In order to neglect individual
      differences, the coronal scanning was perpendicular to the orbital axis. The
      displacement was measured in the plane 2 mm and 4 mm anterior from the globeoptic
      nerve junction. The distance of the displacement was represented by the distance
      from the center of the globe to the center of the muscle cone. RESULTS: The
      displacement in the plane 4 mm anterior (mean +/- standard deviation) was greater
      in the order of the myopic esotropia group(1.6 +/- 0.64 mm), the high myopia
      group(1.2 +/- 0.51 mm), and the control group(0.059 +/- 0.35 mm). The
      displacement of the eyeball was largest in the myopic esotropia group(p < 0.001).
      The outer axial length and the distance of the displacement in all cases was
      correlated significantly(r = 0.93, p < 0.01). Moreover, the eyeballs of the
      myopic esotropia group and the high myopia group were displaced upwards in the
      temporal area. CONCLUSIONS: The posterior portion of high myopia was displaced
      upwards in the temporal area in the muscle cone regardless of the presence or
      absence of esotropia. The eyeball originally elongates upwards in the temporal
      area, not towards the weakest part of the muscle cone.

PMID- 14969089
TI  - [The surgical outcome of vitrectomy for idiopathic epiretinal membranes and
      foveal thickness before and after surgery].
AB  - PURPOSE: To evaluate the surgical outcome of vitrectomy and foveal thickness
      before and after vitrectomy for idiopathic epiretinal membranes. SUBJECTS AND
      METHODS: Twenty-three eyes of 21 patients with idiopathic epiretinal membranes
      were analyzed. The mean follow-up period was 17.8 months. In 16 eyes of 14
      patients, foveal thickness was measured by optical coherence tomography (OCT).
      RESULTS: Preoperative visual acuity ranged from 0.1 to 0.7. Postoperatively, 17
      eyes achieved a final visual acuity of 1.0 or better, and 21 eyes achieved 0.5 or
      better. Preoperative foveal thickness ranged from 205 to 575 microns (mean +/-
      standard deviation, 409.9 +/- 103.3 microns). Postoperatively, mean foveal
      thickness was 347.7 +/- 106.0 microns (1 week follow up), 338.6 +/- 103.7 microns
      (2 months), 304.6 +/- 97.0 microns (6 months), and 274.3 +/- 78.7 microns (1
      year). There was a weak negative correlation between visual acuity and foveal
      thickness. CONCLUSION: Visual acuity improves significantly after surgery. OCT is
      useful for idiopathic epiretinal membrane surgery.

PMID- 14969090
TI  - [Long-term efficacy and safety of combined topical antiglaucoma therapy--timolol
      & unoprostone vs. betaxolol & unoprostone].
AB  - PURPOSE: To evaluate long-term efficacy and safety of treatment combining topical
      beta-blockers and isopropyl unoprostone in primary open-angle glaucoma and normal
      tension glaucoma patients. METHODS: A prospective, open-label, parallel-group
      clinical comparison trial was performed to evaluate efficacy and safety of
      treatment combining 0.5% betaxolol and 0.12% isopropyl unoprostone (B&U) or 0.5%
      timolol and 0.12% isopropyl unoprostone (T&U). Forty eyes of 40 patients, which
      were matched in the aging and the stage of glaucomatous visual field defect, were
      studied. Twenty patients were treated with B&U and the other twenty patients with
      T&U twice daily for 24 months. Goldmann intraocular pressure(IOP), Humphrey
      automated perimetry, blood pressure, heart rate, and peak flow were done every
      six months in each group. RESULTS: In the B&U treatment group, mean IOP was 21.2
      mmHg at baseline and 18.3 mmHg(p < 0.005) after 2 years, and in the T&U treatment
      group it was 21.1 mmHg at baseline and 17.9 mmHg (p < 0.001) after 2 years. The
      cases in which MD value decreased over 2 dB were one in the B&U treatment group
      and three in the T&U treatment group. The average MD value was significantly
      improved from -7.40 dB to -5.90 dB after 2 years with B&U treatment(p < 0.05),
      but there was no difference with the T&U treatment. None of the patients stopped
      combined therapy because of side effects, though heart rate was significantly
      reduced only in T&U treatment group. CONCLUSION: Both combined treatments were
      effective for IOP reduction in glaucoma patients, and the data from the B&U
      treatment group suggested that B&U was more effective in maintaining visual field
      than T&U.

PMID- 14969091
TI  - [Two cases of Senior-Loken syndrome].
AB  - BACKGROUND: We report two rare cases of Senior-Loken syndrome, one with fundus
      lesions simulating Coats disease. CASE 1: A 14-year-old boy had juvenile
      nephronophthisis and bilateral retinitis pigmentosa with retionochoroidal atrophy
      and salt and pepper fundus. Electroretinogram (ERG) showed non-recordable changes
      and the Goldmann perimeter showed ring scotomas. CASE 2: A 14-year-old boy had
      bilateral retinitis pigmentosa and juvenile nephronophthisis with continuous
      ambulatory peritoneal dialysis. Additionally, both eyes showed massive exudates
      seen in Coats disease in the entire periphery, exudative retinal detachment,
      proliferative changes in the inferior periphery, yellow opacitas corporis vitrei,
      keratoconus, and cataract. The left eye had vitreous hemorrhages. Both eyes
      received vitreous surgery and endophotocoagulation. After the surgery the left
      eye showed neovascular glaucoma and a cyclophotcoagulation was performed. The
      massive edema in the superior retina of both eyes disappeared and intra-ocular
      pressure in the left eye was normalized. However, despite these treatments, both
      eyes finally had no light perception. CONCLUSION: Case 1 was a typical SLS, and
      case 2 was a rare one with fundus lesions simulating Coats disease, keratoconus,
      and cataract. We suspect the exudative changes resulted from various vessel
      changes and choroidal circulatory disturbance of renal retinopathy, retinal
      vascular damage, and destruction of blood-retinal barrier with retinitis
      pigmentosa, the inflammatory changes of vessels, and other things.

PMID- 14969092
TI  - [Ciliochoroidal effusion after remission of lens-induced glaucoma detected by
      ultrasound biomicroscopy].
AB  - PURPOSE: To report the results of ultrasound biomicroscopy(UBM) cases of
      ciliochoroidal effusion after a lens-induced glaucoma attack. CASES: Case 1 was
      an 83-year-old female. She had shallow anterior chamber with expanded cataract
      with exfoliation in her right eye. Intraocular pressure(IOP) of the right eye was
      64 mmHg. On the next day, IOP was reduced to 16 mmHg by conservative therapy. UBM
      showed circumference ciliochoroidal effusion in the right eye. On the 5th day,
      IOP increased to 38 mmHg. UBM was repeated and showed the disappearance of
      ciliochoroidal effusion. On the 9th day, phacoemulsification was done to treat
      the lens induced glaucoma attack. Two weeks after operation, IOP of the right eye
      was 6 mmHg and UBM showed ciliochoroidal effusion. Case 2 was an 85-year-old
      female. She had been diagnosed by an ophthalmologist as having an attack of lens
      induced glaucoma in her left eye. IOP was 46 mmHg. When she was referred to us,
      IOP was decreased to 24 mmHg and ciliochoroidal effusion was observed in her left
      eye by UBM. CONCLUSION: We report two cases of ciliochoroidal effusion associated
      with lens-induced glaucoma attack. UBM is useful to observe changes in the
      ciliary body after lens-induced glaucoma attack.

PMID- 14969093
TI  - [A good course of retinopathy of prematurity in an infant weighting 398 g at
      birth].
AB  - BACKGROUND: Recently neonatal mortality of ELBW infants has improved remarkably,
      but the difficulty in preventing severe retinopathy of prematurity(ROP) or
      blindness implies that fundamental causes are still not resolved. CASE: We
      encountered a case of ROP with a very good natural course in a very low birth
      weight(398 g) infant. CONCLUSION: This case suggests the possibility of
      predicting the course of ROP in extremely low birth weight(ELBW) infants weighing
      less than 500 g, and of improving their management.

PMID- 14969094
TI  - [Program for Continuing Professional Education in Ophthalmology. A review 17
      viral eye diseases].

PMID- 14969095
TI  - [Videofluorography of the pharynx in patients suffering from aspiration
      pneumonia].
AB  - We evaluated videofluorographic recordings of the pharynx (VF) in patients
      suffering from aspiration pneumonia. The patients consisted of 55 men and 6 women
      who consulted the ENT Department at Kumamoto University Hospital between May 1994
      and February 2002. Surgery for an upper alimentary tract malignancy (16 patients)
      was the most frequent background feature. The number of patients with
      cerebrovasucular disease and neuronal/neuromuscular diseases were 11 and 12,
      respectively. VF enabled the misswallowing of barium into the trachea to be
      visualized in 38 patients. Of these 38 patients, 20 exhibited misswallowing
      during or after the pharyngeal stage of swallowing. Among the 23 patients in whom
      misswallowing was not detected, 13 had upper alimentary tract diseases. The VF
      findings suggested the presence of gastroesophageal clearance after swallowing.
      Gastro-esophageal regurgitation may be a significant factor, in addition to the
      silent aspiration of oral and pharyngeal secretions during the night as a trigger
      of recurrent aspiration pneumonia.

PMID- 14969096
TI  - [Tympanoplasty on only hearing ears].
AB  - The management of only hearing ears remains controversial because of the risk of
      postoperative hearing deterioration. We reviewed 12 cases of hearing ears alone
      operated on at the Hyogo College of Medicine Department of Otolaryngology from
      1999 to 2002. All ears were dry at the final examination. Postoperative hearing
      results were evaluated based on the guideline of the Japan Otological Society
      (2000). An air bone gap within 15 dB was found in 9 cases (75%), hearing gain
      exceeding 15 dB was found in 6 cases (50%), the hearing level was within 30 dB in
      4 cases (33.3%), and total successful cases numbered 10 (83.3%). Eight patients
      wore hearing aids before surgery, and 4 patients (50%) did not need them after
      the surgery. We suggest that tympanoplasty by skillful surgeons should be done to
      obtain a dry ear, to avoid a progressive hearing loss, to preserve or improve
      hearing, and to improve the quality of life. We also suggest that handling of
      ossicles should minimized in chronic otitis media and cholesteatoma.

PMID- 14969097
TI  - [A statistical analysis of epistaxis between outpatients and inpatients].
AB  - Although we found several statistical studies on epistaxis, we found no reports
      discussing clinical differences in nasal bleeding between outpatients and
      inpatients. We therefore examined 103 inpatients (1998-2001) and 337 outpatients
      (2001) with epistaxis for gender, age, season, bleeding points, and blood
      pressure. We then compared these parameters statistically in both groups using
      Mann-Whitney's U test. The incidence of epistaxis in inpatients was statistically
      higher in winter than in any other season, and most had uncontrolled borderline
      hypertension. We concluded that borderline hypertension worsens in winter and
      that patients with borderline hypertension should be medicated to prevent severe
      epistaxis.

PMID- 14969098
TI  - [Histological study on the effects of ethanol injection on mouth mucosa
      contraction loss].
AB  - We previously reported that a loss of contraction in the mucosal tissue of the
      palate arch is effectively induced by ethanol injections of moderate
      concentration and dosage. The present study was performed to obtain more
      information on how such ethanol injections induce contraction loss in mucosa
      tissue. Guinea pigs of both sexes were used in this study. The left arch of the
      palate mucosa was injected with 2 microliters of 70% ethanol and used as the
      experimental group. The right arch of the palate mucosa of the same animal was
      injected with saline and used as a control. One, three, five, eight, 10, 30, 50,
      and 90 days after injection, the mucosal tissues that received the injection were
      resected under anesthesia and processed for light microscopy using standard
      procedures. One day after the ethanol injection, severe coagulative degeneration
      of the mucosal tissue of the palate was seen. However, the damaged area was
      strictly restricted to the arch of the palate. Coagulative degeneration of the
      tissue peaked three days after the injection. Thereafter, the mucosal epithelial
      and mucosal connective tissues regenerated, and the damaged mucosal tissue
      quickly began to repair. An apparent cicatricial contraction loss was observed 10
      days after the ethanol injection, along with the progression of fibrotic changes
      in the submucosal connective tissue of the arch of the palate. The regenerative
      action of the mucosal arch of the palate abated 30 days after the ethanol
      injection, and the reduced mucosal tissue appeared to have become denser as a
      result of an increase in dense fibrous connective tissue in the submucosal layer.
      No cell malignancies were seen throughout the entire 90-day observation period.
      In conclusion, cicatricial contraction loss of the mucosal arch of the palate
      resulting from the injection of an appropriate concentration and dosage of
      ethanol leads to the regeneration of the mucosal epithelium and fibrotic changes
      in the submucosa. The ethanol injection described here seems to be extremely
      safe, since it exerted no malignant effects on the cells and tissues either
      morphologically or functionally.

PMID- 14969099
TI  - [Overview: molecular mechanisms of sex determination and differentiation in
      animals--generality and diversity].

PMID- 14969100
TI  - [Switching mechanism from asexual to sexual reproduction in planarians].

PMID- 14969101
TI  - [Sex determination mechanism in the silkworm, Bombyx mori, compared with that in
      Drosophila].

PMID- 14969102
TI  - [Sex determination, gonadal sex differentiation and sex change in fish].

PMID- 14969103
TI  - [Sex determination in reptiles and amphibians: with special reference to the
      mechanism of temperature-dependent sex determination].

PMID- 14969104
TI  - [Sex differentiation of the mammalian gonad].

PMID- 14969105
TI  - [In situ observation on the protein folding dynamics by small angle X-ray
      scattering].

PMID- 14969106
TI  - [Chondroitin sugars in embryonic cell division of the nematode C. elegans].

PMID- 14969107
TI  - [Roles and regulations of an Arabidopsis homeobox gene, GL2 in epidermal cell
      development].

PMID- 14969108
TI  - [Significance of a study on potassium channels by Dr. Roderick MacKinnon, a
      winner of the 2003 Nobel Prize in Chemistry].

PMID- 14969109
TI  - [World trends of the bioinformatics and the systems biology: rapid change towards
      the integration of the analyses of genome, protein and biological systems].

PMID- 14969110
TI  - [Bioinformatics for breeding].

PMID- 14969111
TI  - [What can and cannot be patented: useful invention].

PMID- 14969112
TI  - Homicide--still too high.

PMID- 14969113
TI  - Comparing sex offender risk assessment measures on a UK sample.
AB  - The purpose of this study on 139 sex offenders was to consider the application of
      six measures of risk: Static-99, SACJ-Min (Structured Anchored Clinical Judgment
      Scale-Minimum), RRASOR (Rapid Risk Assessment for Sexual Offence Recidivism),
      Risk Matrix 2000-Sexual/Violent, and SVR-20 (Sexual Violence Risk-20) and to
      compare risk assessments conducted by a Regional Secure Unit (RSU) and the
      Probation Service. Levels of risk for the RSU sample ranged from 1% to 42% low
      risk to 1% to 66% high risk compared with the Probation sample of 8% to 43% low
      risk to 4% to 70% high risk. Offenders with adult victims obtained significantly
      higher scores using the RM2000/S and SACJ-Min than did those with child victims
      who obtained significantly higher scores on the RRASOR. Sex offenders referred to
      a RSU scored significantly higher on RRASOR and RM2000/S than did sex offenders
      supervised by the Probation Service. Forensic practitioners may be better served
      if risk measures assess specific subcategories of sexual offenders.

PMID- 14969114
TI  - Nonsex offenses committed by child molesters: findings from a longitudinal study.
AB  - This study, which used a prospective as well as a retrospective methodology,
      examined the criminal records of 30 child molesters prior to, and up to 10 years
      after an index event of sexual abuse for which they were convicted: 73% had
      convictions for other offenses, 60% had convictions for offenses other than sex
      offenses, 50% had convictions for property offenses, 27% had convictions for
      offenses involving violence, and 23% had convictions for drug offenses. Offending
      levels for nonsex offenses were significantly higher than the general adult male
      population. Any theory concerning the dynamics of sex offending against children
      needs to account for the level of nonsex offenses committed by child molesters.

PMID- 14969115
TI  - Pervasive developmental disorders, psychiatric comorbidities, and the law.
AB  - Scattered reports propose that pervasive developmental disorders (PDDs) are risk
      factors for criminal behavior, yet the association between PDD and delinquent
      behavior is untrue for the majority of patients. However, individuals with PDDs
      may be at risk for legal trouble in the presence of comorbid psychopathology, and
      not solely on the basis of their developmental disability. This article analyzes
      theoretically the relationship between complex developmental disorders and
      delinquency with the hypothesis that the delinquent behaviors reported in it
      resulted from comorbid psychopathology and not as a direct consequence of a
      developmental disorder. A small series of patients diagnosed with a PDD and
      comorbid psychiatric illnesses whose admission to the hospital was precipitated
      by delinquent behavior is presented.

PMID- 14969116
TI  - The Risk Assessment Program and the Court of Penal Execution in the Province of
      Buenos Aires, Argentina.
AB  - This study describes the working of a new system that supervises the execution of
      the punishment phase in the Province of Buenos Aires, Argentina; namely, the
      Court of Penal Execution, as well as the risk assessment program. It also reports
      the results of the violent recidivism baseline risk assessment carried out in
      candidates for conditional release. The cohort studied was recruited during 18
      months in the Judicial Department of La Plata, taking into consideration
      psychopathological and criminological variables. The Psychopathy Checklist
      Revised (PCL-R), the Historical, Clinical, and Risk Management--20 (HCR-20), and
      the Violence Risk Appraisal Guide (VRAG), among others, were used as measures.
      During the study period, 65 candidates for conditional release were part of the
      baseline assessment, and they constitute the population of this study. The
      measures' mean scores were PCL-R, 20.57; HCR-20, 18.58; VRAG, 12.17.

PMID- 14969117
TI  - Ritual homicide during dissociative trance disorder.
AB  - A case report is described of a man who developed a single period of recurrent
      episodes of dissociative trance disorder (DTD) during a family stress. The
      cultural environment was permeated by thoughts and beliefs in magic. During one
      trance state, the man performed an exorcism on the 6-month-old baby of his
      brother-in-law, and the baby died from cerebral hemorrhage. In the 5-year follow
      up, no other episodes of DTD developed, and the man is serving an 18-year
      sentence.

PMID- 14969118
TI  - The effects of criminal justice contact on employment stability for white-collar
      and street-level offenders.
AB  - Criminologists increasingly have studied the effects of criminal justice contact
      on a broad range of offenders' adult outcomes. However, virtually all of this
      research focuses exclusively on street-level offenders. With the use of a unique
      data set that includes street-level and white-collar offenders, we investigated
      the odds of regaining steady employment following criminal justice contact by
      offender type. Specifically, we investigated the effects of age of onset, number
      of prior arrests, total time sentenced, timing of first arrest, and timing of
      first incarceration on employment stability for both types of offenders, while
      controlling for family background factors, race, educational attainment, and age.
      Overall, we found that white-collar offenders are better able to rebound
      following contact with the criminal justice system. However, when the accrue
      multiple arrests and are arrested or incarcerated before the age of 24, white
      collar offenders face the same obstacles to employment stability as their street
      level counterparts.

PMID- 14969119
TI  - Concurrent cross-validation of the Self-Appraisal Questionnaire: a tool for
      assessing violent and nonviolent recidivism and institutional adjustment on a
      sample of North Carolina offenders.
AB  - The aim of this study was to determine whether the Self-Appraisal Questionnaire
      (SAQ), a tool that was found to be reliable and valid for assessing violent and
      nonviolent recidivism and institutional adjustment for Canadian offenders, would
      also be valid for the same purposes with a demographically different population
      of North Carolina offenders. The internal consistency alphas and SAQ total and
      subscale scores' correlations were high. Offenders with high SAQ total scores had
      significantly more violent offenses, had more total number of past offenses, had
      higher numbers of past arrests, and had more institutional infractions than those
      with low SAQ scores. There were no significant differences between the responses
      of the African American and Caucasian offenders on the SAQ scales. These results
      support previous findings regarding the reliability and validity of the SAQ for
      assessing recidivism and institutional adjustment and suggest that the SAQ could
      be used with diverse populations.

PMID- 14969120
TI  - Personality typologies of male juvenile offenders using a cluster analysis of the
      Millon Adolescent Clinical Inventory introduction.
AB  - The Millon Adolescent Clinical Inventory (MACI) is a unique adolescent instrument
      that attempts to delineate between personality and acute symptoms. This study
      sought to explore typologies based on the Personality Pattern scales of the MACI
      in a sample of detained male juvenile offenders (N = 103). A Ward's method
      cluster analysis yielded a four-cluster solution, and each cluster was provided a
      clinically relevant label: (a) disruptive, antisocials; (b) agreeable,
      antisocials; (c) anxious, prosocials; and (d) reactive, depressives. The largest
      group consisted of the reactive depressives (n = 41). This suggests the
      importance of considering the role of internalizing problems as a conduit to
      delinquency in addition to antisocial personality. No interaction between cluster
      membership and offense history or race was found.

PMID- 14969121
TI  - Euthanasia: another face of murder.
AB  - Debate over euthanasia is not a recent phenomenon. Over the years, public
      opinion, decisions of courts, and legal and medical approaches to the issue of
      euthanasia has been conflicting. The connection between murder and euthanasia has
      been attempted in a few debates. Although it is widely accepted that murder is a
      crime, a clearly defined stand has not been taken on euthanasia. This article
      considers euthanasia from the medical, legal, and global perspectives and
      discusses the crime of murder in relation to euthanasia, taking into
      consideration the issue of consent in the law of crime. This article concludes
      that in the midst of this debate on euthanasia and murder, the important thing is
      that different countries need to find their own solution to the issue of
      euthanasia rather than trying to import solutions from other countries.

PMID- 14969123
TI  - Disinfection protocol.

PMID- 14969124
TI  - Presidential perspectives: change: a key to opportunity.

PMID- 14969125
TI  - Impact of tracheostomy or laryngectomy on spousal and caregiver relationships.
AB  - Caregiving is an important component in the management of patients with a
      tracheostomy or laryngectomy. The purpose of this integrative research literature
      review was to gain a better understanding of the impact of caregiving for adults
      and children with laryngectomy or tracheostomy on the patient, the family, and
      the caregiver. Patients who had undergone laryngectomy or tracheostomy included
      those with and without cancer. This integrated review of the literature on
      caregiving in this population demonstrates the dearth of studies on this subject.
      Despite the significance of the caregiving role, few studies have addressed
      caregiving, and those that have are primarily descriptive. Studies are needed
      that develop and test interventions to assist caregivers in adaptation to their
      role, identification of methods of decreasing caregiver burden and strain, and
      coordination of resources to support patients and caregivers of patients with
      tracheostomies and laryngectomies.

PMID- 14969126
TI  - Follow-up quality of life assessment in patients after head and neck surgery as
      evaluated by lay caregivers.
AB  - OBJECTIVE/HYPOTHESIS: As rehabilitation after head and neck surgery is
      increasingly dependent upon caregivers with no formal training (lay caregivers),
      the lay caregiver's assessment of the patient's quality of life (QOL) status may
      be critical to successful rehabilitative efforts. This study evaluates lay
      caregiver QOL assessment at six and 12 months post-operatively and compares the
      findings to pre-operative assessments. MATERIALS AND METHODS: Twenty-five
      patients undergoing head and neck surgery and their primary lay caregivers
      completed the Medical Outcomes Survey Short Form 36 (SF-36) pre-operatively and
      were followed. Six and 12-month post-operative forms were completed and compared
      for available patient/lay caregiver pairs. Pair assessment was considered
      congruent if the lay caregiver's assessment of each domain of the SF-36 fell
      within the 90th % confidence interval of the patient's score. High congruence was
      defined as congruence between the pairs for six or more of the eight domains.
      Results were also related to previously published preoperative data. RESULTS:
      Fourteen and six patient/lay caregiver pairs completed the six and 12-month
      follow-up forms, respectively. Overall congruence was 55% and 45% at six and 12
      months, respectively, down from 70% found pre-operatively. Forty-two percent and
      17% of the patient/lay caregiver pairs were highly congruent at six and 12
      months, respectively. Both values were below the 60% high congruence value noted
      pre-operatively. The trend toward lay caregivers underrating general health was
      maintained, while overrating of bodily pain leveled at six months and returned at
      12 months. Same generation pairs demonstrated a steady decrease in high
      congruence levels at six and 12 months. Recurrent disease status no longer
      predicted high congruence at six or 12 months. CONCLUSION: Trends predicting high
      congruence in patient/lay caregiver QOL assessment identified preoperatively were
      not maintained in the post-operative evaluations, except the underrating of
      patients' general health status. Lay caregiver ability to accurately assess
      patient QOL status did not improve and, in fact, appeared to worsen. Further
      study into lay caregiver assessment of patients' quality of life status following
      head and neck surgery is warranted. Efforts should be directed toward the use of
      standardized assessment tools and anticipation of subject dropout with greater
      subject recruitment.

PMID- 14969128
TI  - Notice of proposed bylaw revisions for the College and Association of Registered
      Nurses of Alberta (CARNA).

PMID- 14969127
TI  - Taber RNs playing a key role in changing health-care delivery.

PMID- 14969129
TI  - [Selected issues of gene therapy in cardiology].
AB  - Gene therapy is one of the challenges in the medicine. The advance, which had
      been achieved in a molecular biology through last ten years, brought to the first
      clinical trials of gene therapy. This treatment method may find a big application
      in cardiology, for example: cardiomyopathy, restenosis and ischaemic heart
      disease. The main problem in the gene therapy is to supply a therapeutic gene to
      target cell of the patient and to express it. Clinical effectiveness of the gene
      therapy has not been proved yet so, therefore it is necessary to carry out more
      new designed researches, which would enable to accept the gene therapy as an
      effective treatment. Using the gene therapy beside social and ethic problems
      gives a lot of law's doubts.

PMID- 14969130
TI  - [Early and mid-term evaluation of the pulmonary autograft function in adolescents
      and adults].
AB  - The aim of this study was to establish the indications to use of pulmonary
      autograft in the treatment of aortic valve disease in the adolescents and adults;
      early and mid-term an evaluation of autograft's function and function of left
      ventricle after Ross operation. In this procedure the patient's own pulmonary
      valve is removed together with the main trunk of the pulmonary artery and used to
      replace the aortic valve. Pulmonary homograft is used to reconstruction of right
      ventricular outflow tract. Between February 1994 and march 2001 in 1st Cardiac
      Surgery Department in 43 patients over 14 years of age Ross operation have
      performed. Mean age was 24.9 years. Indications for operation were predominant
      aortic stenosis in 29 patients, aortic incompetence in 7 patients, and complex
      aortic valve disease in 7 patients. Hospital mortality was 4.6%. In mid-term
      observation 41 patients left. All survivors remained in New York Heart
      Association functional class I and were free of complications and medications. In
      the all patients autograft's valve have functioned excellent (without or small
      regurgitation). Echocardiographic parameters of left ventricular function
      improved in the all patients. The indications to pulmonary autograft insertion in
      the adolescents and adults are small aortic ring, infective endocarditis and
      contraindications to anticoagulants using. The early and mid-term results confirm
      a high efficacy Ross operation in this age's group with low mortality. It
      completely relieves the abnormal loading conditions of the left ventricle,
      resulting in a complete recovery of left ventricular function.

PMID- 14969131
TI  - [Diagnostic and prognostic significance of homocysteine determined in acute phase
      of myocardial infarction].
AB  - THE AIM: Of this study was to assess the serum homocysteine concentration in
      subjects with acute myocardial infarction and its correlation with the course of
      infarction and further prognosis considering particularly left ventricle
      dysfunction, heart rate and conduction disorders as well as to assess the
      usefulness of metionin load test as a prognostic test in patients with myocardial
      infarction. MATERIAL AND METHODS: 66 patients were studied: 36 with recent
      myocardial infarction and 30 healthy individuals as a control group. Fasting
      serum homocysteine and its concentration two hours after metionin load were
      determined in all patients. They all underwent echocardiographic examination,
      stress test and 24-hour Holter monitoring. The study revealed a significant
      positive correlation between increased serum homocysteine concentration in
      patients with myocardial infarction and worsening of contractility parameters,
      extent of infarction area, and negative correlation between homocysteine
      concentration and ejection fraction. CONCLUSIONS: On the basis of the study
      outcome we can make a statement that increased homocysteine concentration in
      patients with acute phase of myocardial infarction indicates its more severe
      course, more extensive disorders of myocardium kinetics, more significant left
      ventricle diastolic and systolic dysfunction. Increased serum homocysteine in
      metionin load test indicates higher death risk in patients with myocardial
      infarction.

PMID- 14969132
TI  - [Mental stress test in patients with stable coronary artery disease].
AB  - Myocardial ischemia may be triggered by exercise and non-exercise stimuli. THE
      PURPOSE: Of this study was to determine the usefulness of laboratory mental
      stress (MS) in inducing myocardial ischemia and/or cardiac arrhythmia in patients
      (pts) post myocardial infarction, with stable coronary artery disease. Sixty four
      men, mean age 45 +/- 6 years underwent: 15 min mental stress test during 24 h
      Holter monitoring and exercise stress testing. RESULTS: Only 8 pts (13%) had
      positive mental stress test (MS+). Five of them had ST segment depression > 1.0
      mm (STD), and the remaining 3 pts had cardiac arrhythmias. All episodes were
      silent. MS+ pts had higher heart rate (HR) during the mental test than those with
      negative stress test (MS-) (120/min vs 105/min, p < 0.05). In contrast, at least
      one episode of daily life ischemia (DLI) was recorded in 23 pts (36%) on Holter
      monitoring. In MS+ pts average duration of DLI (17 min) and mean HR during
      ischemia (124/min) were greater than in MS-pts (respectively 10.5 min and 94/min,
      p < 0.05). Exercise induced ischemia (STD > 1.0 mm) was observed in 29 of 64 pts
      (45%). However, in MS+ pts exercise duration (708 +/- 132 s), time to 1 mm STD
      (432 +/- 108 s) were significantly shorter and double product at 1 mm STD (13,400
      +/- 2913 mm Hg/min) was lower than in MS- pts (respectively 924 +/- 174 s, p <
      0.01; 624 +/- 162 s, p < 0.01; 14,800 +/- 3321 mmHg/min, p < 0.05). CONCLUSIONS:
      Mental stress test is a weak inducer of ischemia and arrhythmia in patients with
      stable coronary artery disease. Patients with mental stress-induced ischemia are
      more likely to display ischemia during daily life and exercise stress testing.

PMID- 14969133
TI  - [Selected hematopoietic cytokines in patients with colorectal cancer].
AB  - We have investigated the serum level of selected hematopoietic cytokines, such as
      interleukin 3, granulocyte-macrophage--colony stimulating factor (GM-CSF),
      granulocyte--colony stimulating factor (G-CSF) and macrophage--colony stimulating
      factor (M-CSF) in colorectal cancer patients. Also correlations between their
      concentrations and stages were made. The study was done on group consisted of 30
      diagnosed colorectal cancer patients. The used classification of stage of the
      tumor was described by Dukes. The results were compared with control group
      consisted of 20 healthy persons. The examined factors were assayed by ELISA
      method. In colorectal cancer patients the serum levels of IL-3, GM-CSF and M-CSF
      were increased in comparison with the control group. The differences between
      cytokines concentrations in control group and colorectal cancer patients were
      statistically significant for GM-CSF and M-CSF. The serum levels of cytokines
      were higher in more advanced tumor stage. This results permit for further study
      on usefulness of these cytokines as a markers for colorectal cancer.

PMID- 14969134
TI  - [Analysis of cloning rearrangement of T-cell receptor gamma gene in primary
      cutaneous lymphoma].
AB  - The aim of the study was to evaluate the usefulness of the T-cell receptor (TCR)
      gamma gene rearrangement analysis in the diagnosis of mycosis fungoides (MF) and
      Sezary syndrome (SS). The analysis of TCR gamma gene rearrangements was performed
      in patients with MF/SS in different stages and in subjects with inflammatory
      dermatoses as the control group, using the method of polymerase chain reaction
      with subsequent separation of products by temperature gradient gel
      electrophoresis. Dominant clones with TCR-gamma rearrangement were detected in
      86.5% of MF/SS skin biopsies and in 67.5% of MF/SS peripheral blood cells whereas
      in control group in 12% and 15% respectively. Statistically significant
      differences were found in the occurrence of clonal T-cells in skin infiltrates
      between patients with MF/SS and control group. Statistical analysis of TCR-gamma
      rearrangement in peripheral blood cells did not revealed any differences only in
      patients with early stage (IA) of MF when compared with inflammatory dermatoses.
      Detection of T-cell receptor gamma gene rearrangement is a valid supplement to
      histopathological and immunohistochemical examination in cases suspected of MF/SS
      however the diagnosis should always be based on the analysis of examinations and
      clinical stage of patients.

PMID- 14969135
TI  - [Alcohol dependence in schizophrenia and legal issues].
AB  - The study was undertaken to investigate, reported in earlier studies significant
      link, between schizophrenia, alcohol dependence and penalty. A representative
      sample was selected from schizophrenic patients with diagnosis of alcohol
      dependence hospitalized in psychiatric hospital in Choroszcz in the period of
      1998-2000. They were compared with non-alcohol-abusing control patients with
      schizophrenia. All subjects were assessed for life-time legal problems using
      detailed questionnaires, family interviews and case histories. Patients with
      schizophrenia and alcohol dependence engaged more often in criminal activity.
      Personality disorders and history of head traumas might have contributed to an
      increase of antisocial behavior.

PMID- 14969136
TI  - [Helicobacter pylori infection and its influence on Parkinson disease].
AB  - The aim of this study was to determine the frequency of Helicobacter pylori (H.
      pylori) infection and its influence on the symptoms of Parkinson's disease. The
      study group consisted of 58 people with Parkinson's disease aged 49 to 83 years
      old, and 26 of their spouses. Percentage of people infected by H. pylori was
      similar between people with Parkinson's disease and their spouses. In the same
      time in this study percentage of people infected by this bacterium was lower than
      in other studies of polish population. There was no relation between Parkinson's
      disease and H. pylori infection in the investigated group of patients suffering
      from Parkinson's disease.

PMID- 14969137
TI  - [Evaluation of the immune system following splenectomy in childhood: preliminary
      study].
AB  - The authors would like to point out a possibility of immune system disturbances
      (especially lymphocyte T), severe infection occurring in patients following
      splenectomy. Five children following splenectomy due to severe spherocytosis were
      studied. In all children serum level of IgA, IgG, IgM immunoglobulins, phagocytic
      index, Hamburger count and lymphocyte antigen surface expression CD3, CD4 CD10,
      CD19, CD20, CD29, CD45RA, CD56 were evaluated. In comparison to control group,
      median numbers of lymphocyte T CD3 (p < 0.05), lymphocyte CD4 (p < 0.05),
      lymphocyte T CD4CD29 (p < 0.001) and percentage of cells reacting with z
      CD4CD45RA (p < 0.001) were significantly lower in splenectomized children,
      whereas number of NK cells occurred to be noticeable higher (p < 0.001).
      Immunoglobulins' levels, Hamburger count, phagocytic index and percentage of
      lymphocyte CD8, CD19 and CD20 did not differ between groups. On the basis of the
      results, the authors recommend the necessity of routine vaccination in this group
      of patients against most common pathogens.

PMID- 14969138
TI  - [Usefulness of Doppler ultrasound imaging in monitoring of hypoxic-ischemic
      encephalopathy in preterm infants].
AB  - Cerebral blood flow disregulation could be one of the main causes of hypoxic
      ischaemic encephalopathy (HIE). It is difficult to differentiate between
      sonographic appearance of immature periventricular white matter of premature
      neonate and changes of HIE type. Therefore the diagnostic and prognostic value of
      doppler ultrasound resistance index (RI) examination in anterior cerebral
      arteries of premature infants with early sonographic signs of periventricular
      white matter hyperechogenicity was the aim of the study. The study group
      consisted of 23 premature infants: birth weight 1550 +/- 570 g, gestational age
      24-32 weeks, Apgar score 2-7 points, of which 19 were ventilated. Doppler
      ultrasound imaging was performed twice: during the first 24 hours of life and 3
      weeks later. As not all infants survived to the time of control examination, the
      final study group consisted of 17 subjects. Doppler examination of premature
      infants having finally sonographic signs of HIE (n = 12) revealed that RI value
      in this group of infants was increased during initial as well as the next
      examination. In the group of premature infants having finally normal sonographic
      scan (n = 5), doppler examinations showed that RI value stayed in normal limits
      or was slightly decreased all the time. We conclude that doppler imaging of
      premature infants could be important diagnostic and prognostic tool in
      differentiating between the ultrasonographic view of immature periventricular
      white matter and real HIE. Doppler imaging is useful in identification of
      patients having increased risk of HIE and supplements routine transfontanellar
      ultrasound in estimation of HIE progression.

PMID- 14969139
TI  - [Flavonoids: antioxidative compounds and their role in prevention of ischemic
      heart disease].
AB  - Research on the biological activity of flavonoids shows that they are powerful
      antioxidants. The paper discusses the physical and biological factors which are
      fundamental to the antioxidant properties of these compounds. Experimental,
      clinical and epidemiological studies have shown that consumption of large amounts
      of food rich in polyphenolic compounds (such as vegetables, fruit, juices, tea,
      spices) may prevent or support the treatment of the cardiovascular disease.

PMID- 14969140
TI  - [Molecular basis of oral hypoglycemic sulfonylurea action].
AB  - Sulfonylureas are commonly used antidiabetic oral agents. They act through a
      receptor in the beta cell membrane, which is called the sulfonylurea receptor 1
      (SUR1). SUR1 together with Kir 6.2 protein assembles into a potassium channel,
      playing a key role in the regulation of insulin secretion. The work discusses up
      to date views on the structure and function of sulfonylurea receptors and
      potassium channels as well as clinical implications of their disturbances.

PMID- 14969141
TI  - [Folic acid: new indications for an old well-known drug].
AB  - This review deals with the well known drug--folic acid, for which new indications
      have been discovered in recent years. The drug was used for 50 years in anemia
      megaloblastia, other anemias with bone marrow hypofunction, in leucopenia and
      granulocytopenia, in celiac disease and sprue and folic acid deficit during oral
      anticonceptive drug use. From recent investigations follows that there are strong
      indications for the use of folic acid in a periconceptual period and during
      pregnancy (at least 600 micrograms per day) and during lactation--to prevent
      neural tube defects. To prevent orofacial cleft defects a dose 5 mg a day mast be
      used. Another important new indication is hyperhomocysteinemia. Folic acid, B12
      and B6 vitamins are involved in the metabolic removal of homocysteine, but folic
      acid deficit occurs the most often. The results of hyperhomocysteinemia are
      increased risk of arteriosclerosis coronary heart diseases and stroke. RESULTS:
      Folic acid is an important factor in preventing congenital defects (especially of
      the neural tube) and for lowering the risk of coronary heart disease and stroke
      due to hyperhomocysteinemia (together with vitamins B6 and B12).

PMID- 14969142
TI  - [Rare forms of hypertension].
AB  - In recent years there has been a growing interest in rare forms of secondary
      hypertension. Data from these studies enlarge our knowledge of hypertension
      pathophysiology and make possible establishing new possibilities of hypertension
      treatment. Primary reninism, Liddle's syndrome and neurovascular contact has been
      presented in the article. The pathogenesis, clinical symptoms and treatment of
      these rare forms of hypertension is discussed in this article.

PMID- 14969143
TI  - [The influence of simultaneous pancreas and kidney transplantation on long-term
      diabetic complications in patients with insulin dependent diabetes mellitus].
AB  - Diabetic nephropathy affects 20-35% patients with diabetes mellitus. After 25-30
      years of nephropathy, chronic renal failure (CRF) develops in these patients. The
      aim of the study is to present the influence of simultaneous pancreas and kidney
      transplantation (SPK) on long-term diabetic complications in patients with CRF in
      course of insulin dependent diabetes mellitus and the length and quality of life
      of these patients. SPK has positive influence on nerves function of peripheral
      and autonomic nerve system, as well as heart ventricle function, but brings only
      limited benefits as regards progression of diabetic retinopathy and nephropathy.
      The life time of the patients in which SPK was performed is significantly longer
      that in dialysed patients treated with insulin and patients, in which only
      cadaveric kidney transplantation was performed. In patients after SPK an
      improvement of quality of life is also observed. SPK should be considered at the
      moment of appearance of renal failure symptoms in patients with long lasting
      insulin dependent diabetes mellitus. Proceeding like this may significantly
      improve prognosis in this patients, outstandingly disadvantageous if only
      intermittent dialysis is applied.

PMID- 14969144
TI  - [Epidemiology and therapy of infections caused by Neisseria meningitidis].
AB  - In spite of the progress in antibiotic therapy and immunoprophylaxis Neisseria
      meningitidis remains one of the major causes of meningitis and sepsis burdened by
      high mortality. In this paper characteristics of N. meningitidis and in
      particular its epidemiology, virulence factors, antibiotic therapy and resistance
      mechanisms, immuno- and chemoprophylaxis, are discussed. Data from the National
      Reference Centre for Bacterial Meningitis are also presented. These data indicate
      that this pathogen is the most common laboratory confirmed bacterial etiologic
      agent of community-acquired meningitis in Poland.

PMID- 14969145
TI  - [The biological role and properties of some water soluble vitamins].
AB  - Vitamins are a group of compounds indispensable for the development, normal
      growth and functioning of the human body. Lack of vitamins causes serious
      diseases for human, even though small amounts of them are required to maintain
      good health. Therefore there is growing interest concerning the role of vitamins
      in physiological conditions. This article reviews the role of vitamins (water
      soluble): PP, B6 and C in metabolic processes, discuss criteria used for
      recommended ingestion of the vitamins, and presents recommendations for these
      vitamins intake. In this paper we discussed vitamins in detail including their
      chemical structure, chemical activity and biological properties.

PMID- 14969146
TI  - [Chemokines and their participation in leukemic cells migration].
AB  - Impaired migration of leukocytes is characteristic feature of leukaemias.
      Knowledge of the mechanisms of leukaemia cells migration has expanded greatly in
      recent years. Leukocytes infiltrates are formed in surrounding tissues due to
      changes in chemokines and adhesion molecules concentrations. The adhesive
      interactions of cells with other cells and between cells and with the
      extracellular matrix are started by activation leukaemic leukocytes by specific
      chemokines. There are four groups of chemokines receptors: CXC, CC, C and CX3C.
      Unfortunately pathological processes of cells activation in the curse of
      leukaemias have not been fully explained yet. The paper presents current opinions
      about structure and role of some chemokines and their receptors in leukaemic
      cells migration.

PMID- 14969147
TI  - [The influence of prostaglandins on metastases development].
AB  - Arachidonic acid metabolites including prostaglandins (PG) participate in many
      biological processes and play regulatory functions. The significant role of PG in
      physiological and pathological process is well known and described by many
      authors. Prostaglandins were demonstrated to have local hormone properties and
      often exert an antagonist effect. Despite years of research the role of PG in
      cancer diseases development is still poorly understood. The article is focused on
      the influence of arachidonic acid metabolites and its analogs on tumor growth and
      metastases formation.

PMID- 14969148
TI  - [Diabetic cardiomyopathy].
AB  - In the last decades, due to the growing number of new cases of diabetes and its
      cardiovascular complications, much attention has been paid to diabetic
      cardiomyopathy. The studies on the etiology of this condition have confirmed the
      role of advanced glycation end products, lipoprotein a Lp(a), apolipoprotein B
      (apo B) and the changes in the intracellular calcium levels. An insight in the
      natural history of left ventricular diastolic and systolic dysfunction in
      diabetes has been made possible thanks to the widespread availability of
      echocardiography. Diastolic dysfunction, characteristic of diabetes, precedes the
      onset of systolic dysfunction, which reveals at a later stage, first as exercise
      induced abnormalities. The influence of diabetes on morphology of the heart
      manifests as hypertrophy of the left ventricle, especially in non-insulin
      dependent diabetes and enlargement of the left atrial chamber. The results of the
      studies are not decisive as to the possible correlation between the severity of
      the diastolic dysfunction and the duration of diabetes or the quality of
      metabolic control. The presence of significant coexisting conditions, including
      hypertension and the complications of diabetes such as autonomic neuropathy is
      associated with more pronounced symptoms of diastolic dysfunction and higher
      values of corrected QT interval and dispersion which are considered to be the
      most important predictors of mortality in diabetic patients.

PMID- 14969149
TI  - [Current opinions on the pathogenesis of demyelinating diseases. Part II].
AB  - Demyelinating diseases include a group of disorders in which destruction or
      degeneration of normal myelin occurs. In most cases these processes go on without
      primary lesion of axons. Demyelinization appears as a consequence of different
      pathogenetic factors like ischemia, injury, toxins and radiation. In this review
      a current view on the pathogenesis of demyelinating diseases is discussed,
      considering the achievements of molecular biology.

PMID- 14969150
TI  - [Dapsone in skin diseases].
AB  - This article reviews mechanism of action, adverse effects, drug interactions of
      dapsone and its application in dermatology. Dapsone belongs to sulfones group and
      is mainly recommended in skin diseases where gathering of neutrophiles or
      eosinophiles are found.

PMID- 14969151
TI  - [Alcohol and risk for the cancer].
AB  - Chronic alcohol consumption is associated with an increased risk for cancer
      especially of the upper aerodigestive tract and also liver, colorectum and
      breast. The role of ethanol alone and acetaldehyde in the etiology of many
      cancers is evident. The concentrations of ethanol and acetaldehyde after alcohol
      drinking depend on the activity of two main enzymes. The one is the alcohol
      dehydrogenase (ADH) and the next aldehyde dehydrogenase (ALDH). The different
      isoenzymes of ADH and ALDH genetically encoded have different catalytic
      properties. Therefore, the polymorphism of these enzymes might be an risk factor
      for cancer in the case of chronic alcohol consumption.

PMID- 14969152
TI  - [Ultrasonography of the hand in rheumatoid arthritis].
AB  - Authors present the ability of ultrasonography and Color and power Doppler
      sonography in evaluation of the hand structures in patients with rheumatoid
      arthritis. Imaging of bony contours allows to identify bone erosions. Thickness,
      oedema and presence of increased blood flow (hyperaemia) in the synovium in
      joints and tendon sheaths are characteristic features of an active inflammation.
      Changes of the tendon structure indicate its damage. US allows to image the
      carpal tunnel structures, to visualise changes of the median nerve in the carpal
      tunnel syndrome and gives possibilities to find the cause of its compression.

PMID- 14969153
TI  - [The methods of hyperhidrosis treatment].
AB  - Physiological sweating from cutaneous eccrine glands maintains normothermia and
      skin hydratation. Hyperhidrosis, a pathological condition caused by excessive
      secretion of the eccrine sweat glands, is divided into physiologic, symptomatic
      and idiopathic type. Contemporary methods of hyperhidrosis treatment, in
      particular botulinum toxin injections are discussed.

PMID- 14969154
TI  - [Antibodies against TSH receptors (TRAb) as indicators in prognosing the
      effectiveness of Tiamazol therapy for Grave's Disease].
AB  - The aim of the study was to evaluate the usefulness of TRAb determinations in
      prognosing and monitoring the efficacy of conservative treatment in Graves'
      disease. The examinations were performed in 54 patients. During the 18-month
      observation all the patients were treated with Tiamazol. The control group
      consisted of 20 healthy volunteers. The TRAb levels were determined before as
      well as 12 and 18 months after thyrostatic treatment. Simultaneously, the levels
      of TSH and FT4 were analysed. Moreover, all the patients underwent ultrasound
      examinations to assess the size of the thyroid gland. The findings of the 18
      month follow up showed that in 31 patients (57%) the thyroid function became
      normal (group I--euthyreosis), in 23 patients (43%) hyperactivity persisted
      (group II--hyperthyreosis). The TRAb levels were analysed in both groups of
      patients. An increased initial level of TRAb was found in the hyperactivity group
      mean -54.39 + 31.21 U/l which was statistically significantly different from the
      TRAb levels in the euthyreosis group mean -29.13 +/- 19.14 U/l and in controls
      mean -2.75 +/- 2.06 U/l (p < 0.001 for both parameters). After 12-month treatment
      increased values of antibodies were still observed in this group of patients
      (mean -39.96 +/- 33.40 U/l) in comparison with the euthyreosis group (mean -9.87
      +/- 8.33 U/l) and controls (mean -2.75 +/- 2.06 U/l) (p < 0.001 for both
      parameters). After 18-month treatment the TRAb levels in group II remained
      increased (mean -40.17 +/- 33.06) while in group I normal levels were achieved.
      The sizes of the thyroid gland were compared between the individual groups. In
      the hyperactivity group after 18-month treatment, the thyroid size was the
      biggest (mean -41.09 +/- 13.94 ml) and was statistically significantly different
      when compared to the average size in the euthyreosis group mean -31.65 +/- 11.74
      ml (p < 0.01) and in controls mean -14.45 +/- 2.37 ml (p < 0.001). The levels of
      antibodies against TSH receptors are useful parameters in prognosis and
      monitoring the treatment effectiveness in Graves' disease. High initial levels of
      antibodies are the poor prognostic factors. The TRAb determinations are of some
      prognostic value not only before but also 12 months since the onset of therapy.
      The lack of antibody level normalization during treatment is connected with
      persisting hyperactivity. The TRAb concentration correlates with the thyroid
      size.

PMID- 14969155
TI  - [Cancer cachexia syndrome in patients with lung cancer].
AB  - Cancer cachexia syndrome is a common and important complication of cancer. It
      occurs in 30% to 80% cancer patients. It includes anorexia, loss weight, weakness
      and impaired immune function. The cause of the syndrome stays still unclear. Many
      endocrinological and metabolic abnormalities are observed, like hypermetabolism,
      glucose intolerance, increased proteolysis and lipolysis. Main role in the
      development of cancer cachexia is played by cytokines: TNF, interleukin 1 and 6,
      interferon alfa and gamma. The aim of the study was to collect information about
      cachexia in lung cancer patients, treated in Department of Pulmonology, Wroclaw
      Medical University. We observed 76 patients with recent diagnosis of lung cancer
      (43 male, 33 female), 50 patients with non-small lung cancer and 26 with small
      lung cancer. Average age 61 +/- 9.76. We divided all patients in four groups,
      depending on percent of weight loss and compared these groups. We estimated
      extent of disease, anthropological and biochemical parameters. Among all patients
      we found cachexia in 23 (32%). There were only some differences between patients
      with and without cachexia. Bigger loss weight was observed in older men.
      CONCLUSIONS: Cachexia syndrome is not an important problem in lung cancer
      patients at the time of diagnosis.

PMID- 14969156
TI  - [Clinical usefulness of high-dose oral nitroglycerin in patients with stable
      angina pectoris].
AB  - The aim of this study was to evaluate clinical efficacy and adverse effects of
      nitroglycerin 15 mg in slow-release form (N-15) after single ingestion. In
      randomized, double-blind and placebo (P) controlled with cross-over design study
      15 male patients with stable angina received N-15 or P. Antianginal efficacy of
      the drug was evaluated by analysing the parameters of tolerance of effort and
      coronary reserve taken from serial exercise stress tests on treadmill performed
      preceding single oral ingestion, 2 hours and 6 hours after. Simple hemodynamic
      parameters were also evaluated in the rest and during exercise. N-15
      significantly improved in comparison to P: total walking time both after 2 hours
      by 34.3% (p < 0.01) and 6 hours by 23.1% (p < 0.01); walking time to angina after
      2 hours by 34.8% (p < 0.01) and 6 hours by 21.7% (p < 0.05), and walking time to
      ischemia after 2 hours by 66.1% (p < 0.01) and 6 hours by 39.0% (p < 0.05). N-15
      significantly increased the rest heart rate in standing position 2 hours after
      ingestion by 12.3% (p < 0.01) and decreased rest systolic blood pressure in both
      positions 2 hours after ingestion: in supine by 12.9% (p < 0.01) and standing by
      16.3% (p < 0.01) and after 6 hours: in supine by 9.1% (p < 0.05) and standing by
      10.0% (p < 0.05). No postural hypotension in any patient occurred. Diastolic
      blood pressure was significantly decreased only in standing position 2 hours
      after N-15 ingestion by 12.3% (p < 0.01) and after 6 hours by 9.1% (p < 0.05).
      During maximal exercise significant reduction of systolic blood pressure occurred
      2 hours after ingestion and significant reduction of diastolic blood pressure
      occurred both 2 hours and 6 hours after ingestion. Adverse effects after single
      ingestion of N-15 were the few: the headaches were presented only in 4 patients
      (27%), and in 53% patients any adverse effect occurred. Nitroglycerin 15 mg in
      slow-release form is an active coronary drug, effective not less than 6 hours
      after ingestion, and its adverse effects are the few.

PMID- 14969157
TI  - [Increased cerebrovascular reactivity and risk factors for ischaemic stroke in
      patients with inadequate circulation in the posterior circle of Willis].
AB  - Since ischaemic stroke (IS) is very widespread, a rapid development of ultrasound
      diagnostic techniques searching the relationship between cerebral circulation
      efficiency and pathophysiology of ischemic lesions is observed. The aim of our
      study was to evaluate blood flow velocity (BFV) and cerebrovascular reactivity
      (CVR) of some anterior circulation arteries (MCA) and posterior circulation
      arteries (PCA, VA) in relation of IS risk factors in patients with posterior
      circulation insufficiency. MATERIAL AND METHODS: The study group consisted of 40
      patients (13 female, 27 male) of mean age 56.9 +/- 12.9 yr. Neurological
      examination, brain CT and TCD were performed in each patient. All patients
      underwent TCD examination including evaluation BFV of both MCA's, PCA's and VA's
      using TC 2020 Pioneer (EME). Control group consisted of 22 healthy volunteers of
      mean age 59.6 +/- 6.3 yr. RESULTS AND CONCLUSIONS: BFV and CVR of MCA, PCA, VA in
      examined patients were similar compared to controls. CVR of MCA's were not
      significant different compared to CVR of PCA's and VA's. Impaired CVR may be
      connected with ischaemic heart disease and TIA, while coexisting arterial
      hypertension may cause increased CVR.

PMID- 14969158
TI  - [Discrepancy of results in estimation of serum specific IgE levels against
      inhalant allergens by two dipstick methods].
AB  - Two dipsticks methods of semiquantitative estimation of serum specific IgE
      Allergodip (Allergopharma) and Allergoset (Intex AG) have been compared. 494
      estimations of specific IgE (sIgE) have been performed in the serums of 26 atopic
      patients. In 62% of cases both methods gave the results in the same class, in 21%
      the difference was 1 class only, but in 16% the great discrepancy of results was
      observed (difference of 2 or more classes). However in 115 cases (230 results)
      sIgE levels appeared to be within normal limits. The remained results proved that
      Allergoset test regarding different allergens gave 32-56% lower results of sIgE
      than Allergodip test. The differences concerning 8 inhalant allergens are
      presented graphically.

PMID- 14969159
TI  - [Burning mouth syndrome].
AB  - Burning mouth syndrome (BMS) is currently described as a burning pain in the
      tongue or other parts of mucous cavi oris without pathological signs of mucous
      cavi oris and changes in laboratory blood tests. On the basis of the current
      literature and our patients' examinations we described the incidence, etiology,
      symptoms and offered model of treatment of BMS.

PMID- 14969160
TI  - [Usefulness of examining the vaginal ecosystem and its importance in threatening
      premature labor].
AB  - The aim of the study was to examine whether, and in what extend bacterial
      vaginosis (BV) might be the cause of threatening premature labor. Vaginal
      ecosystem was examined in the group of 225 pregnant women with the symptoms of
      threatening premature labor. The control group consisted of women with
      physiologically proceeding pregnancies. Bacterial vaginosis was confirmed in
      14.2% of pregnant women with the symptoms of premature labor, whereas BV was
      found in 10.2% of women in the control group. The examination of BV seems to be
      useful in all pregnant women, especially in those with threatening premature
      labor.

PMID- 14969161
TI  - Antioxidant status in newborns and infants suffering from congenital heart
      defects.
AB  - There is a common view that free radicals may play an important role in tissue
      damage resulting from circulatory insufficiency, cardiosurgery etc. There are
      very few data concerning the involvement of free radical reactions in the
      newborns and infants suffering from congenital heart defects (CHD). Antioxidant
      status was evaluated in 41 newborns and infants under 1 year of age, among them
      23 suffering from CHD (14 with left-to-right shunt and 9 with cyanotic heart
      defect) and 18 healthy controls. The study based on the assessment of activities
      of antioxidant enzymes in blood (superoxide dismutase, catalase and glutathione
      peroxidase), levels of low molecular weight antioxidants (vitamin E, uric acid
      and selenium) and the concentration of malondialdehyde (MDA) as a marker of lipid
      peroxidation. All subjects had low blood selenium concentration as compared to
      the level considered as being adequate. Infants suffering from CHD had lower, as
      compared to healthy controls, plasma vitamin E concentration. The difference was
      significant in the case of acyanotic ones. The activities of superoxide dismutase
      and catalase in infants with CHD were not significantly different from the
      respective values recorded in healthy controls. The activity of glutathione
      peroxidase in whole blood was the lowest in infants with cyanotic heart defect in
      whom lipid peroxidation, as evaluated by MDA level, was the most enhanced.
      Significantly higher plasma concentration of uric acid which may be interpreted
      as a positive mechanism enabling better protection of red blood cells from
      peroxidative damage was found in this group of infants. It is concluded that
      enhanced oxidative stress due to imbalance between prooxidant and antioxidant
      reactions appears to be associated with congenital heart defect pathology in
      infants.

PMID- 14969162
TI  - [Selected risk factors of thrombotic complications in patients with ulcerative
      colitis].
AB  - We have analyzed the prothrombotic risk factors in 124 patients with ulcerative
      colitis (UC) as compared with control subjects with other gastrointestinal
      disorders. The patients were hospitalized from 1991 to 2000 in the Department of
      Internal Medicine. Platelets level was significantly higher (p < 0.001) in UC
      patients as compared with control group, and aPTT was significantly (p < 0.05)
      prolonged respectively in UC patients as compared with control group. In the
      prospective pilot study we observed the decrease of plasma antithrombin level
      and/or decrease of protein S in approximately 22% of UC patients. The plasma
      protein C activity was normal in all UC patients, whereas the mean level of
      protein S was significantly lower (p < 0.02) in UC patients as compared with
      controls. Thus our data indicate that coagulation abnormalities are potential
      risk factors of thromboembolic complications in UC. Plasma cholesterol and
      triglyceride levels were above upper limit of normal values in 38% and 18% UC
      patients respectively, but mean values of both parameters were not significantly
      different between UC and control group. Our results suggest that plasma lipid
      changes are not independent risk factor of vascular complication in UC. In UC
      patients smokers were observed 4 times less than no-smokers. However, positive
      correlation between smoking and rise of hematocrit (F = 4.48; p < 0.05) in UC
      suggests that smoking may be a risk factor of vascular complications in the
      disease. Thromboembolic events were found in 1.6% of UC patients. In addition,
      chronic coronary heart disease was accompanied approximately 6% of UC patients.
      Evaluation of prothrombotic risk factors and associated ischaemic heart diseases
      may have prognostic value in the management of UC.

PMID- 14969163
TI  - [Early and subsequent results of operation of trivalvular diseases].
AB  - The aim of the thesis is the evaluation of efficacy of surgical treatment for
      complex valvular heart diseases. An inclusion criterion to this analysis was the
      performance of a mitral valve replacement (MVR) and aortic valve replacement
      (AVR) for an artificial valve and a tricuspid valve replacement or plastic
      operation (TVR or pl. TV). Such operative procedures were carried out
      simultaneously. Twenty five operations were performed from 1995 to 1999. TVR was
      carried out in 2 patients, pl. TV in 21 patients and the Revuelt method was
      adopted for this purpose, whereas in two cases a tricuspid valve plastic
      operation was performed sewing in the annulus. In the two cases the
      revascularization of the right coronary artery was carried out simultaneously. In
      another case a myxoma removal from the left atrium was additionally carried out.
      One patient died due to renal failure during hospitalization on the 9th day after
      the operation. Three patients died subsequently in the first, second and third
      year after operation. The causes of subsequent deaths among the patients examined
      in the period of five years after the operation were thrombotic-embolic
      complications. CONCLUSIONS: Early and subsequent results of simultaneous tri
      valvular operations are good. The most frequent and difficult postoperative
      complication in this group of patients is a low output syndrome. Subsequent
      complications and deaths are most often due to thromboembolic complications,
      therefore a particular attention should be paid to the anticoagulant treatment in
      this group of patients.

PMID- 14969164
TI  - [Epidemiology of rheumatic fever].
AB  - Rheumatic fever is a systemic inflammatory sequel of the upper respiratory tract
      infection with beta-hemolytic group A streptococci. The disease is characterized
      by joint, heart and subcutaneous tissue inflammation and the nervous system
      involvement. The incidence of rheumatic fever decreased in the 20th century but
      periodical resurgences and local epidemics were reported. The disease is still a
      significant health problem in developing countries.

PMID- 14969165
TI  - [Umbilical cord blood--invaluable source of stem cells].
AB  - The aim of the study was to discuss the role of stem cells in the organism. The
      paper presents the significance of stem cells in the treatment of many diseases,
      such as hematopoietic system disorders, muscular dystrophies, Parkinson disease,
      and congenital immunodeficiency syndromes. The results of investigations on stem
      cells carried out in recent years allow to presume, that the usage of stem cells
      will turn out to be a breakthrough in the history of medicine. Umbilical cord
      blood can be the source of stem cells, which is now underestimated and very often
      removed.

PMID- 14969166
TI  - [Depot medroxyprogesterone acetate (DMPA) injectable contraception--safe,
      effective but neglected method of family planning in Poland].
AB  - As it is known from demographical prognosis for Poland, in the nearest years
      significant increase of the number of women in the childbearing age is expected
      (reflecting high, postwar, demographical wave). In spite of that, the prognosis
      of the number of live births is low, and does not exceed 450 thousands. The
      reason for this phenomenon is the change of life style among young people. They
      postpone delivery of the first baby, and use modern contraceptives. It is also
      expected that the number of women using modern contraceptives (especially
      combined oral contraceptives: estrogen + progestin) should significantly rise. It
      is well known, that with the age of a woman, there is an increasing number of
      contraindications for the estrogen use. It is the sufficient reason to think
      about alternate methods of contraception. DMPA (DEPO-PROVERA-150) is the very
      effective and safe method of family planning. It is used in many countries all
      over the world, since the sixties, but it is almost unknown in Poland. The use of
      DMPA is not reserved only for special cases. After many years of experience, it
      is possible to select the best candidates for this injectable contraception
      (patients with contraindications for estrogens, lactating women, smokers-
      especially over 35 years of age etc). DMPA appears to be acceptable method of
      fertility regulation. Clinical evidence after more than 30 years of use shows no
      additional adverse effects and possibly fewer than in the case of other hormonal
      methods of contraception. The particular advantages of DMPA, as a highly
      effective, long-lasting and reversible contraceptive, make it important option
      for Polish women, desiring a modern method of fertility regulation.

PMID- 14969167
TI  - [Drugs ototoxicity. Part II. Loop diuretics, nonsteroidal anti-inflammatory
      drugs, antineoplastic and antimalarial drugs ].
AB  - Ototoxicity has been recognized since the 1800, when it was learned that quinine
      and acetylsalicylic acid provoked dizziness, tinnitus and hearing loss. Beside
      above mentioned other drugs also have joined the list of ototoxic substances:
      aminoglycoside antibiotics, loop diuretics or antineoplastic drugs. In this
      review pharmacological and toxicological properties of potentially ototoxic
      drugs, such as loop diuretics, nonsteroidal anti-inflammatory drugs
      (salicylates), antineoplastic and antimalarial drugs are presented.
      Pathophysiology and postulated mechanisms causing drug-induced ototoxicity are
      also discussed.

PMID- 14969168
TI  - [Ramsay Hunt syndrome--a case study].
AB  - In this work we present a patient, aged 40 with Ramsay Hunt syndrome, who was
      treated at the Department of Infectious Disease, Medical Academy in Lublin
      (Poland). The diagnosis of the disease was based on the anamnesis concerning
      epidemiology of the disease, the course and three major symptoms: facial
      paralysis, neuralgia, herpetic eruption in the mouth and on the ear. The combined
      treatment with antiviral drugs and corticosteroids was partially successful and
      did not resolve the seventh nerve palsy.

PMID- 14969169
TI  - [X-linked agammaglobulinemia (XLA) associated with agranulocytosis--case report].
AB  - In this case study authors presented the clinical characteristics of X-linked
      agammaglobulinemia (XLA) associated with agranulocytosis diagnosed in a 2-year
      old boy. Affected child lacked circulating mature B cells, presented low levels
      of serum immunoglobulins, but did not suffer from recurrent bacterial infections.
      XLA is a primary immunodeficiency caused by a defective tyrosine kinase (Btk) in
      B cells. Our patient and his mother have a mutation in the BTK gene, described as
      W281X. During therapy with intravenous gammaglobulin, the boy has not experienced
      agranulocytosis. It is important to consider a primary immunodeficiency diagnosis
      when a child presents agranulocytosis or neutropenia and a recurrent infectious
      disease.

PMID- 14969170
TI  - [Nasopharyngeal angiofibroma images with intracranial extension].
AB  - Nasopharyngeal angiofibroma is a benign, highly vascular, nasopharyngeal tumour.
      It causes the erosion of bony structures of the skull base and extends into nose,
      paranasal sinuses, pterygo-pallatine fossa and infratemporal fossa. In some
      patients intracranial invasion is present. Authors presented three cases of
      nasopharyngeal angiofibroma with intracranial extension treated in their centre.
      The clinical details of these cases and discuss the problems related to the
      diagnosis and management of this pathology were described.

PMID- 14969171
TI  - [Glaucoma Service Database].
AB  - We present the common problems related to clinical databases. The Glaucoma
      Service Database created in our clinic is an attempt of developing the optimal
      medical database. The system organizes our repository of clinical data. It
      consist of 3 modules: 1) the users list with predefined privileges and rights, 2)
      lists of coded data for further use, that facilitate filling in the fields, 3)
      clinical details of all patients. The user interface of our database is very
      simply, thus it is very easy to use it even by unskilled staff. The accuracy of
      data is protected by system's internal algorithms. It could be used to
      investigate clinical epidemiology, risk assessment, post-marketing surveillance
      of drugs, practice variation and decision analysis. Data from Glaucoma Service
      Database can also help in the management of health service.

PMID- 14969172
TI  - Pilocytic astrocytoma.

PMID- 14969173
TI  - Cytologic features of pilocytic astrocytoma in cerebrospinal fluid specimens.
AB  - OBJECTIVE: To illustrate the cytomorphologic features of pilocytic astrocytoma
      (PA) in cerebrospinal fluid (CSF) samples. STUDY DESIGN: A search of records from
      1965 to 2001 was performed to identify all patients with a diagnosis of PA in
      whom CSF samples were examined. Slides from CSF samples originally reported as
      atypical, suspicious or positive were reviewed and the cytomorphologic features
      assessed. RESULTS: Two hundred ninety-three patients with a diagnosis of PA were
      identified. Of these, 44 had a total of 65 cytologic preparations of CSF. In 34
      patients (77.2%) the CSF cytology was negative, in 5 (11.4%) either atypical or
      suspicious, and in 5 (11.4%) positive for neoplastic cells. The tumors in the 5
      positive cases arose in the cerebellar hemispheres (2), cerebellar vermis (1),
      thalamus (1) and tectum with extension into the fourth ventricle (1). All
      positive samples were hypercellular, with an average of 5 cell clusters per case
      (range, 3-11). The clusters were composed of cohesive epithelioid cells with a
      mean of 8 cells per cluster. In addition, some cases had scattered, isolated,
      single cells. These single neoplastic cells had prominent, hairlike cytoplasmic
      processes. The cells in clusters appeared epithelioid, with oval nuclei, mild
      nuclear pleomorphism, finely or slightly coarsely granular chromatin and
      cobweblike cytoplasm. CONCLUSION: The cytomorphologic features of PAs
      recapitulate their histologic characteristics. The tumor cells are recognizable
      in CSF samples and readily distinguishable from histiocytes and ependymal cells.

PMID- 14969174
TI  - Role of biliary brush cytology in primary sclerosing cholangitis.
AB  - OBJECTIVE: To assess the role of brush cytology in the routine evaluation of
      patients with primary sclerosing cholangitis (PSC). STUDY DESIGN: From January
      1995 to June 2000, 64 brush cytology specimens were obtained from 21 patients who
      had at least one cytologic sample obtained during endoscopic retrograde
      cholangiography. All patients had a diagnosis of primary sclerosing cholangitis.
      Cases were classified as benign, atypical or malignant according to major
      cytologic criteria (nuclear contour and chromatin irregularities) and minor
      cytologic criteria (polarity, cellularity, nuclear enlargement, mitosis,
      increased nuclear/cytoplasmic ratio) used by us to diagnose biliary brush
      cytology. Follow-up was available in all cases. RESULTS: Diagnoses were benign
      (13), atypical (5) and malignant (3) on cytology. Follow-up of the 13 benign
      cases showed bile duct stones (2), gallbladder adenocarcinoma at cholecystectomy
      (1), ascending cholangitis (1) and clinically/cytologically by benign follow-up
      (9). Five of 13 benign cases had subsequent liver transplantation for liver
      failure, with explants showing changes of primary sclerosing cholangitis. Of the
      3 malignant cases, 1 had carcinoma in situ on biopsy, with the explanted liver
      showing high grade dysplasia; the second patient had cholangiocarcinoma on
      explant; and the third had hepatocellular carcinoma on liver five needle
      aspiration. The 5 patients with atypical cytology were reclassified on review as
      reactive (3) and atypical not otherwise specified (2). Follow-up showed benign
      disease in 3 of 3 atypical cases reclassified as reactive; 2 of 2 reclassified as
      atypical not otherwise specified showed low grade dysplasia in the explant.
      CONCLUSION: The overall incidence of malignancy was low (3 of 21) in patients
      with PSC. Bile duct brushing is a sensitive method of detecting neoplasia in the
      setting of PSC when well-defined cytologic criteria are applied.

PMID- 14969175
TI  - Dedicating specific sessions of cytopathology courses to medical students. A
      survey/consensus study.
AB  - OBJECTIVE: To establish a consensus among medical schools in North America on
      whether to dedicate specific sessions to teaching cytopathology to medical
      students. STUDY DESIGN: A list of all the medical schools in the United States,
      Canada and Puerto Rico was retrieved from the American Association of Medical
      Colleges Web site in conjunction with the information provided by the 33rd
      edition of the Directory of Pathology Training Programs, published by the
      Intersociety Committee on Pathology Information. A total of 147 schools were
      found. A questionnaire was designed to include 7 questions addressing this issue
      and was sent to each medical student pathology course director. RESULTS: Of the
      147 questionnaires, 65 (44%) responses were received. Fifty-four (83%) indicated
      the total number of pathology lectures given to medical students in each course.
      The number of lectures ranged between 19 and 201, with a mean of 85. Seven (11%)
      stated that their systems used problem based learning and that therefore a
      specific number of pathology lectures could not be given accurately. Sixteen
      (25%) have cytology sessions incorporated in their pathology courses. Thirteen
      (20%) prefer to include cytopathology sessions in the course and are committed to
      doing so. Therefore, 29 (45%) institutions either have or prefer to have specific
      sessions dedicated to cytopathology education. CONCLUSION: Incorporating specific
      sessions dedicated to cytopathology education in the medical student curriculum
      is highly recommended. Using new educational techniques, including computer-based
      methods with real case studies, would add more educational value.

PMID- 14969176
TI  - Use of a liquid-based, thin-layer Pap test in a community hospital. Impact on
      cytology performance and productivity.
AB  - OBJECTIVE: To evaluate the direct-to-vial efficacy of the SurePath Pap test
      (TriPath Imaging, Burlington, North Carolina, U.S.A.) in a community hospital
      laboratory and to assess its impact on productivity, as measured by Pap test
      turnaround times (TATs). STUDY DESIGN: A total of 8,771 SurePath Pap tests were
      compared to 5,055 conventional Pap smears collected and processed over the same
      12-month period. SurePath histologic correlation rates were compared to
      historical correlation rates for conventional Pap smears. Pap test TATs for 3
      months prior to implementing SurePath were compared to TATs for the last 3 months
      of the study, which included an approximate 70:30 ratio of SurePath to
      conventional Pap tests. Laboratory staffing was unchanged, and mean monthly
      accessions were relatively constant. RESULTS: SurePath showed statistically
      significant improvements in the detection of low grade (LSIL) (196%) and high
      grade (HSIL) (243%) squamous intraepithelial lesions (SILs) relative to
      conventional Pap smears. The atypical cells of undetermined significance (ASCUS)
      rate remained nearly constant with SurePath, while the ASCUS/SIL ratio decreased
      by 68%. Unsatisfactory rates declined 81%. Histologic correlation rates with
      SurePath increased over those of conventional Pap smears. Pap test mean TATs
      improved 73% with SurePath. CONCLUSION: Sure-Path detected significantly more
      cases of LSIL and HSIL than conventional smears without compromising specificity.
      The ASCUS/SIL ratio and unsatisfactory rate declined dramatically. Pap test TATs
      also improved markedly with SurePath.

PMID- 14969177
TI  - External quality assurance for cervical cytology in developing countries.
      Experience in Peru and Nicaragua.
AB  - Given interest from the professionals concerned, an external quality assurance
      scheme for cervical cytology can successfully be introduced in developing
      countries. This is a very important precondition if screening programs are to be
      expanded and decreases in mortality from cervical cancer are to occur in
      developing countries. Nicaragua and Peru have been experimenting with an external
      quality assurance system adapted from the Scottish and Northern Ireland scheme.
      It has been received with enthusiasm and acceptance and has helped cytology
      laboratories in these countries focusing on quality issues. Nevertheless, a
      successful quality control scheme that is to result in improvements in the
      quality of professionals' diagnostic skills needs to be accompanied by a remedial
      program for subperformers.

PMID- 14969178
TI  - Malignant melanoma metastatic to the liver. A cytomorphologic comparative study
      to identify reproducible diagnostic criteria.
AB  - OBJECTIVE: To establish cytomorphologic criteria that might facilitate the
      identification of malignant melanoma (MM) cells with epithelioid (nevoid)
      morphology, in fine needle aspiration biopsy material from the liver. STUDY
      DESIGN: Aspirated material from 18 cases of MM with epithelioid features and 24
      cases of benign liver lesions (BLL) were examined. The cases were selected based
      on the availability of corresponding tissue biopsies, adequate cell block
      material or sufficient number of direct smears to perform immunocytochemical
      staining. The presence or absence of 7 cytologic criteria were reviewed, and the
      results were evaluated by multivariate regression analysis. RESULTS: All
      evaluated criteria were significant for identifying MM cells and differentiating
      them from reactive hepatocytes (P < .001). Uniform atypia, cell dyscohesion,
      eccentric nuclei and irregular nuclear membranes supported MM, whereas,
      monolayered sheets or cordlike arrangement; coarse, granular cytoplasm; and
      occasional transgressing endothelium in true tissue fragments were evidence of
      BLL. CONCLUSION: A systematic evaluation of the cytomorphologic features
      described in this study, in conjunction with the clinical and radiologic
      findings, can be used to render an immediate, confident and accurate diagnosis of
      MM metastatic to the liver.

PMID- 14969179
TI  - Fine needle aspiration biopsy of vertebral lesions.
AB  - OBJECTIVE: To evaluate the accuracy of fine needle aspiration biopsy (FNAB) in
      the diagnosis of vertebral lesions. STUDY DESIGN: Eighty-nine FNAB cases of
      vertebral lesions from January 1996 to December 2001 were retrieved from the
      Allegheny General Hospital laboratory information system. The cases were reviewed
      and correlated with clinical findings, including previous clinical history,
      primary site of malignancy and final pathologic diagnosis. RESULTS: ENAB
      diagnoses were malignant in 43 cases, benign in 35, suspicious in 1,
      unsatisfactory in 7 and false negative in 3. Previous clinical history included
      malignancy (37 patients), osteomyelitis and systemic disease (11), and
      nonspecific or no history (41). In 34 cases (38.2%) both aspirates and core
      biopsies were available, and the diagnoses correlated in 29/34 cases (85%).
      Surgical or core biopsies in the unsatisfactory/suspicious group showed
      malignancy in 4 cases (50%). The sensitivity of FNAB of vertebral lesions was
      96%, specificity 100%, positive predictive value 100% and negative predictive
      value 92%, with no false positive cases. CONCLUSION: FNAB of vertebral lesions is
      an effective, sensitive and specific procedure in the diagnostic workup of a
      patient with or without a prior history of malignancy. Surgical pathology
      examination, including core biopsies of unsatisfactory or suspicious lesions, can
      further improve the diagnostic yield.

PMID- 14969180
TI  - Cytologic features of clear cell carcinoma of the female genital tract.
      Diagnostic value of the "raspberry body" in nonexfoliative cytologic specimens.
AB  - OBJECTIVE: To evaluate the presence of basement membrane stromal material in fine
      needle aspiration (FNA) and scrape cytologic specimens from patients with clear
      cell carcinoma (CCC) of the female genital tract. STUDY DESIGN: The study group
      consisted of 6 patients with CCC (5 ovarian and 1 cervical). Four samples
      corresponded to FNA specimens and 3 to scrape material obtained during
      intraoperative consultation for ovarian tumors. FNA was performed on a pelvic
      recurrence and on liver, pulmonary and lymph node metastases. The 6 cases had a
      complete histopathologic study. RESULTS: In addition to large, clear cells, all
      cases showed basement membrane stromal material that assumed several forms. The
      most common was globular, hyaline structures, either naked or surrounded by
      neoplastic epithelial cells ("raspberry bodies"). Other fragments were larger,
      with several spherules and elongated prolongations. Scrape material showed
      stromal material resembling reduplicated basement membrane material. In Diff-Quik
      stained smears (QCA, Tarragana, Spain) it showed metachromatic staining with a
      pink to purple color. Its recognition on Papanicolaou-stained smears was more
      difficult since it did not stain or was gray. CONCLUSION: Basement membrane
      stromal material and, more precisely, "raspberry bodies," are a characteristic
      cytologic feature of CCC of the female genital tract. The combination of clear,
      atypical cells and basement membrane stroma is highly specific to this neoplasm
      and can be observed not only in exfoliative specimens but also in FNA and scrape
      samples.

PMID- 14969181
TI  - Polymorphous low grade adenocarcinoma of the salivary gland. Diagnosis by fine
      needle aspiration cytology.
AB  - OBJECTIVE: To describe the fine needle aspiration cytology findings of
      polymorphous low grade adenocarcinoma of the salivary gland. STUDY DESIGN: The
      authors reviewed the cytologic findings of 5 cases of polymorphous low grade
      adenocarcinoma. All cases were confirmed by histologic examination. RESULTS: All
      cases showed similar cytologic findings. The smears had high cellularity with a
      population of mixed epithelial and myoepithelial cells. These cells formed
      branching papillae, sheets and clusters. The epithelial cells were uniform, with
      round to ovoid nuclei; absent or inconspicuous nucleoli; and a moderate amount of
      dense cytoplasm. Occasionally the cells formed spherical structures containing
      hyaline globules. Myxoid matrix, either dispersed in the background or
      interspersed with the cellular elements, was also seen often. CONCLUSION:
      Polymorphous low grade adenocarcinoma should be cytologically differentiated from
      adenoid cystic carcinoma, monomorphic adenoma and pleomorphic adenoma.
      Recognition of subtle cytologic features. may be useful in the differential
      diagnosis.

PMID- 14969182
TI  - Thyroid cell proliferation in Graves' disease. Use of MIB-1 monoclonal antibody.
AB  - OBJECTIVE: To measure thyroid cell proliferation in patients with Graves' disease
      (GD) before and during treatment with antithyroid drugs. STUDY DESIGN: Patients
      were assessed by fine needle aspiration biopsy before (n = 20) and after 4 (n =
      19) and 12 months of treatment (n = 15) with propylthiouracil or methimazole.
      Cell proliferation index (CPI) was estimated by immunocytochemistry using MIB-1.
      CPI was studied in relation to the cytologic parameters of the smears; clinical
      parameters, such as Wayne's Clinical Index (WCI) and time without treatment;
      laboratory parameters, such as 131I uptake and dosage of serum free thyroxin and
      thyroid-stimulating hormone; and thyroid ultrasound. RESULTS: CPI varied from
      0.00% to 25.00% before treatment, 0.00% to 23.00% at 4 months and 0.00% to 14.84%
      at 12 months. CPI median values were 6.50%, 4.30% and 3.30%, respectively (before
      and after 4 months and 12 months of treatment). CPI had a positive correlation
      with WCI and FT4 at 12 months of treatment. CONCLUSION: Thyroid CPI in GD varies
      from case to case. However, due to its decreasing pattern during follow-up and
      its positive correlation with thyrotoxicosis severity, CPI may indicate the
      functional status of the gland and contribute to a better understanding of GD.

PMID- 14969183
TI  - Renal cell carcinoma metastatic to follicular adenoma of the thyroid gland. A
      case report.
AB  - BACKGROUND: Renal cell carcinoma is an unpredictable tumor that can recur many
      years after the original diagnosis and metastasize to uncommon sites, including
      the thyroid gland. Differential diagnosis from primary thyroid tumor is often
      difficult both clinically and pathologically. We report a case of metastatic
      renal cell carcinoma in follicular adenoma of the thyroid gland. CASE: A 48-year
      old woman presented with a 3-cm-diameter, palpable mass in the left lobe of the
      thyroid gland. The patient's history included removal of a left renal mass, which
      was conventional renal cell carcinoma. Fine needle aspiration cytology smears
      contained a few small clusters of polygonal cells with abundant, clear cytoplasm
      and irregular, hyperchromatic nuclei as well as bland-looking thyroid follicle
      cells and stromal cells. A papillary or follicular growth pattern was not
      detected. A cell block made from the aspirated sample was composed mainly of
      clear cells. By immunohistochemical stains, the clear cells were completely
      negative for TTF-1, thyroglobulin, calcitonin and inhibin while equivocally
      staining for cytokeratin, CD10 and galectin-3. The histologic diagnosis was renal
      cell carcinoma metastatic to follicular adenoma of the thyroid gland. CONCLUSION:
      Renal cell carcinoma metastatic to the thyroid may masquerade as a primary
      thyroid neoplasm. A history of prior nephrectomy, the presence of unremarkable
      thyroid follicle cells, the absence of a papillary or follicular growth pattern
      and immunohistochemical study can help differentiating metastatic renal cell
      carcinoma from a primary thyroid lesion with clear cell change.

PMID- 14969184
TI  - Fine needle aspiration cytology of low grade fibromyxoid sarcoma. Report of a
      case with histologic correlation.
AB  - BACKGROUND: Low grade fibromyxoid sarcoma, first described in 1987, is a rare
      sarcoma characterized by a bland and deceptively benign histologic appearance but
      with aggressive behavior. CASE: A 51-year-old female presented with a history of
      a recurrent and slowly growing mass in the left foot. Fine needle aspiration
      biopsy showed an abundant myxoid background with occasional thick bands of
      collagen. Tumor cells present in the myxoid background were spindle shaped, with
      focally mild or a light degree of nuclear enlargement, hyperchromasia and
      pleomorphism CONCLUSION: Low grade fibromyxoid sarcoma has particular cytologic
      features. Besides a careful cytologic evaluation of all the components, clinical
      and radiographic correlation is necessary to make the correct diagnosis.

PMID- 14969185
TI  - Columnar cell variant of papillary thyroid carcinoma. Report of a case with
      cytologic findings.
AB  - BACKGROUND: The columnar and tall cell variants of papillary thyroid carcinoma
      (PTC) are uncommon variants and have generally been regarded as more aggressive
      forms in comparison to the more common classic papillary and follicular subtypes.
      Cytologic diagnosis of these rare variants is elusive since the characteristic
      nuclear features of the usual papillary thyroid carcinoma are very often absent
      or inconspicuous. We present a case of the columnar cell variant of PTC in a
      young woman that demonstrates the diagnostic challenge. CASE: A 24-year-old woman
      presented with a solitary, 3-cm mass in the left aspect of the thyroid. The
      aspirate consisted of a moderately cellular sampling of sheets, papillary
      clusters and microfollicles of cells with oval nuclei and uniform, finely
      granular chromatin. These cells were arranged in a peudostratified manner around
      well-defined fibrovascular cores. There were no intranuclear inclusions or well
      defined nuclear grooves in the cells of the aspirate. There was also absence of
      colloid despite the presence of well-formed follicles. The resected thyroid
      revealed a columnar cell variant of PTC. CONCLUSION: The cytologic features of
      columnar cell-type PTC are at variance with those of classic PTC and are elusive
      in fine needle aspiration cytology. It is the lack of classic cytologic features
      of PTC that is distinctly apparent, yet it is the monomorphism of cells in the
      aspirate, their papillary configuration and their pseudostratification in well
      formed fibrovascular cores that are the keys to the diagnosis.
      Immunohistochemical staining to rule out other thyroid neoplasms can be performed
      to aid in the diagnosis.

PMID- 14969186
TI  - Dermal analogue tumor of the salivary gland diagnosed by fine needle aspiration
      cytology. A case report.
AB  - BACKGROUND: Dermal analogue tumor of the salivary gland is a rare form of
      salivary gland adenoma. Cytologic and histologic findings of 1 case are
      presented. CASE: A 74-year-old-female had a dermal analogue tumor in the parotid
      gland diagnosed by fine needle aspiration cytology (FNAC). Aspiration smears were
      characterized by aggregates of uniform epithelial cells, and cell groups bordered
      on thick, basement membrane-like material. The tumor was excised, and the
      histologic sections confirmed the cytologic diagnosis. CONCLUSION: Dermal
      analogue tumor of the salivary gland has a distinctive cytomorphologic
      appearance, and diagnosis of this neoplasm by FNAC is possible. Preoperative FNAC
      of salivary gland lesions is important in planning the most appropriate type of
      treatment.

PMID- 14969187
TI  - Cytologic features of functioning stromal cells in a yolk sac tumor of the ovary.
      A case report.
AB  - BACKGROUND: Functioning stromal cells are sometimes seen in primary and
      metastatic ovarian neoplasms. However, the cytologic features of functioning
      stromal cells have been described only rarely. CASE: A 19-year-old woman had an
      alpha-fetoprotein-producing ovarian yolk sac tumor with functioning stroma. Her
      preoperative serum testosterone level was elevated. Imprint cytology showed that
      the functioning stromal cells had centrally located nuclei with low
      nuclear/cytoplasmic ratios. Occasionally these cells had vacuolated cytoplasm,
      suggesting the presence of lipids. In sharp contrast, the yolk sac tumor cells
      had more pleomorphic and hyperchromatic nuclei. We were able to distinguish
      between neoplastic and functioning stromal cells on the basis of these findings.
      In addition, immunostaining for inhibin on imprint cytologic slides was of great
      help in identifying functioning stromal cells. CONCLUSION: Because functioning
      stromal cells may unexpectedly induce hormonal effects in a variety of ovarian
      tumors, it is important to identify such cells in cytologic specimens.

PMID- 14969188
TI  - Signet-ring follicular adenoma of the thyroid diagnosed by fine needle
      aspiration. Report of a case with cytologic description.
AB  - BACKGROUND: Follicular cells of the thyroid may undergo squamous, oncocytic or
      clear cell metaplastic changes. Of these, the clear cell change with signet-ring
      formation is the most unusual, and follicular adenoma of the thyroid with signet
      ring formation is extremely rare. We describe for the first time the cytologic
      features of a clear cell adenoma of the thyroid obtained by fine needle
      aspiration (FNA). CASE: A 48-year-old woman in a euthyroid state presented with a
      2-cm, right-sided thyroid nodule. Smears obtained by FNA of the nodule revealed
      clusters of large signet-ring cells in a bloody background. The signet-ring cells
      were round to oval, with large cytoplasmic vacuoles and hyperchromatic, eccentric
      nuclei. Colloid in the background was very scanty. Histologic examination of the
      right hemithyroidectomy specimen revealed a signet-ring follicular adenoma.
      CONCLUSION: Lack of familiarity with signet-ring cell adenoma of the thyroid
      could lead to an erroneous diagnosis of metastatic signet-ring cell carcinoma.

PMID- 14969189
TI  - Fine needle aspiration cytology of metastatic choriocarcinoma presenting as a
      breast lump. A case report.
AB  - BACKGROUND: While choriocarcinoma is a rapidly invasive, widely metastasizing
      malignancy, it responds well to chemotherapy, so it is important to obtain an
      early diagnosis. We report the fine needle aspiration cytology (FNAC) of a case
      of choriocarcinoma metastatic to the breast. CASE: A 48-year-old female presented
      with a cough, hemoptysis and epistaxis. Chest computed tomography revealed
      multiple nodules in both lung fields. Also, a firm, slightly tender mass in the
      lower outer quadrant of the left breast was palpated. The breast mass was
      clinically suspected to be a metastatic lung cancer. FNAC of the breast showed a
      malignant tumor that had been misdiagnosed as a metastatic non-small cell
      carcinoma of the lung. Histologic examination of a nasal biopsy revealed
      metastatic choriocarcinoma. CONCLUSION: The cytologic features of choriocarcinoma
      are quite characteristic, with side-by-side, malignant, mononucleated cells and
      multinucleated giant cells corresponding to cytotrophoblasts and
      syncytiotrophoblasts, respectively. The disease is possible to diagnose by a
      careful examination of FNAC samples.

PMID- 14969190
TI  - Fine needle aspiration diagnosis of extramedullary hematopoiesis resembling
      mediastinal and paravesical tumors. A report of 2 cases.
AB  - BACKGROUND: Extramedullary hematopoiesis is a compensatory phenomenon that occurs
      when normal function of the bone marrow is disturbed. It is most often seen in
      patients with hematologic disorders. Although the sites most frequently involved
      are the spleen, liver and lymph nodes, other organs may be involved. We report on
      2 cases of extra-medullary hematopoiesis mimicking posterior mediastinum and
      paravesical tumors and diagnosed by fine needle aspiration cytology. CASES: Two
      men, aged 72 and 82 years, with hemolytic anemia (thalassemia intermedia and
      idiopathic) presented with solid masses involving the posterior mediastinum and
      paravesical region. The patients underwent computed tomography-guided fine needle
      aspiration. The smears were composed of normal bone marrow elements. Both cases
      were diagnosed as extramedullary hematopoiesis. CONCLUSION: Fine needle
      aspiration cytology is an useful method of diagnosing extramedullary
      hematopoiesis and aids in planning treatment.

PMID- 14969191
TI  - Liquid-based cytology findings of glassy cell carcinoma of the cervix. Report of
      a case with histologic correlation and molecular analysis.
AB  - BACKGROUND: Glassy cell carcinoma is a rare form of poorly differentiated
      carcinoma of the cervix with no obvious squamous or glandular differentiation.
      Its liquid-based cytology findings have not been described before. CASE: A 46
      year-old Filipina presented with vaginal bleeding due to a bulky cervical tumor.
      The liquid-based cytology preparation was of moderate cellularity and contained
      small clusters of polygonal to elongated tumor cells admixed with amphophilic,
      granular, necrotic debris. The malignant cells possessed round to oval nuclei; a
      thin nuclear membrane; finely dispersed chromatin; prominent, solitary nucleoli;
      abundant, cyanophilic cytoplasm; and discrete cell borders. Occasional tumor
      cells showed phagocytosis of polymorphs. The background contained a mixed
      population of inflammatory cells. Eosinophils, though present, were not readily
      identified in the cytologic specimen. There was no evidence of dyskeratosis,
      cytoplasmic vacuolation or koilocytosis. Histologic and ultrastructural
      examination of the tumor biopsy showed classic features of glassy cell carcinoma.
      Molecular analysis using polymerase chain reaction and restriction fragment
      length polymorphism revealed the presence of human papillomavirus (HPV) DNA in
      the liquid-based cytology sample. The HPV genotype, however, did not belong to
      any of the commonly encountered prototypes. CONCLUSION: Glassy cell carcinoma of
      the cervix may show distinct, though subtle, cytomorphologic features in liquid
      based preparations. The findings, however, are slightly different from those in
      conventional cervical smears. Awareness of this rare entity is important, as
      glassy cell carcinoma is often associated with more aggressive clinical behavior.

PMID- 14969192
TI  - Insular carcinoma of the thyroid with a predominant microfollicular pattern: a
      diagnostic pitfall on cytology.

PMID- 14969193
TI  - Significance of spindle-shaped and stellate cells in filter preparations of
      vitreous aspirates.

PMID- 14969194
TI  - Pleural effusion as the first manifestation of pulmonary toxoplasmosis in a bone
      marrow transplant recipient.

PMID- 14969195
TI  - Another step in the right direction! Minister Couillard announces funding for
      training 75 nurse practitioners.

PMID- 14969197
TI  - [Role of herbal teas in the treatment of minor syndromes].
AB  - Tisanes, which include all the home remedies made from medicinal herbs, whether
      these are infusions, teas, decoctions or macerations, continue being of great
      importance and usefulness, both as a sole treatment for minor syndromes or as an
      additional aid to treat acute or chronic illnesses. In tisanes or infusion
      remedies, the principle active ingredients are found in lower concentrations
      which leads to a milder pharmaceutical action, but also provides a lesser degree
      of possible undesirable side effects. In upcoming articles, the author shall
      review the herbs most frequently used for treatment of minor pathology which one
      can easily handle, as an infusion, maceration or decoction, in order to provide
      beneficial effects in our patients and for ourselves. The author shall classify
      these according to their recommended use and pharmaceutical action.

PMID- 14969198
TI  - [Death experience. Antidote against fear to death].
AB  - Fortunately, anthropology has brought to our modern society a higher interest for
      mankind's cultural dimension and the values which each people employ in order to
      make sense out of the changes which occur during our lives. It is this cultural
      dimension which permits men to develop our innate capacities and to become
      humans. However, in order to achieve this, we need experiences which are codified
      and interpreted by a values system which each individual has made his/her own.
      Some of these experiences take place inside cultural mores constructed expressly
      so that they are useful for one's lifestyle; these are known as rites. A rite,
      therefore, is an experience which leaves an impression, which implies social and
      biographical changes, which provides meaning to human beings' universal
      interests. Nonetheless, since rites usually are organized by diverse religions,
      it is convenient, as we enter the 21st Century, to speak about Experiences which
      Activate Structures as means to approach, to come to grasp with, some of the
      great causes of anxiety in humans: death and insanity. These Experiences which
      Activate Structures allow us to subjectively experiment, to conquer our fears and
      to be more conscious of our here and our now. Workshops on the Living Integration
      of One's Own Death are included in this context as an appropriate forum through
      which to approach death with knowledge and serenity, inducing changes in our own
      lifestyle as well and helping us to overcome situations of existential blockage.

PMID- 14969199
TI  - [How to decide in a dilemma. Bioethical?].
AB  - Teaching and research in bioethics help one to understand the keys to modern
      culture, with a large plurality of guidelines, so that one is able to choose the
      most appropriate professional method. With this objective in mind, the author
      suggests one take as a reference a decision making model by which one can acquire
      rigor, depth and perspective, and which provides us a significant level of
      knowledge about science, the natural world, society, and especially, the human
      person. The author reported on this topic at the XXI International Conference on
      Philosophy, celebrated in Istanbul.

PMID- 14969200
TI  - [The traditional and the technological way to die].
AB  - The process of dying is that which takes a living organism from a state of life
      to one of death. This process can be adequately described as part of the process
      and transformation of organic material. But the act of dying for a human being,
      just as a human being's process of life, is not something merely biological; it
      also has an element essential in humans: a social aspect. When a human being
      meets death, various people are involved: the person who dies who is said to
      leave, who goes somewhere, and those who remain, who perhaps have to help this
      first person at a moment when that person might require collaboration. Both the
      person who dies and those who remain must come to terms, must assimilate, the act
      of dying. All participants in the process of death have to come to grasp with the
      reality that by this event one of them abandons his/her place in their social
      relation network. Associated with this radical abandonment, one comes face to
      face with a tradition which relates this parting with the ideas of a soul, God
      and immortality. One also faces how to socially organize the process of death,
      the direct meeting of man with death, which we call the way of dying, as part of
      this final event in one's life.

PMID- 14969201
TI  - [Death].
AB  - Intercultural factors are essential for reflection. In this article, the authors
      deals with a more direct vision on the special edition about Grief and Mourning,
      about the topic which lies in the depths of all of our consciences: death and the
      question what lies beyond death? The author provides us elements to reflect about
      concepts, some accepted in various cases, rejected in others, but always
      polemical, which help us to penetrate farther into the real mystery of life:
      death and what follows death.

PMID- 14969202
TI  - [Support psychotherapy in traumatic situations].
AB  - It seems that a certain consensus exists to speak about a traumatic situation as
      an experience which is made up of a threat on the physical or psychological
      integrity of a person and against which one responds with fear, desperation and
      intensive horror. Different psychological phenomena are involved with the manner
      through which a human being confronts his/her past. In particular, the response
      to traumatic situations, mourning, and blame share their characteristic of being
      an irreversible living reality related to facts, loss or past impacts and it is
      necessary to integrate these in one's life in order to advance; these comprise a
      triangle frequently coexisting and interconnected. Aid for these three situations
      has, therefore, as common elements, two premises: an active task is required by
      the person who suffers this situation; this person must, in some form, desire to
      move ahead. One can not toil in mourning, in a traumatic experience, or in a life
      of blame if these have a positive symbolic value for this person; for example,
      mourning as a manner not to treason the dead person by forgetting that person,
      the reliving a trauma as an attempt to provide some sense to the actions which
      occurred, or blame as a desire to not forget an error or as a final punishment of
      this active task; the final objective of this active task is not usually to
      forget but to integrate in order to live. If a person does not perceive this
      clearly, this person may not become actively involved in the task to overcome a
      traumatic situation and to move ahead, nor will that person accept that a person
      who tries to help questions this person's realities or experiences.

PMID- 14969203
TI  - [Bereavement related to the death of a close relative. Nursing care].
AB  - The authors publish a consensus document designed to assist nursing professionals
      to recognize and work with bereavement related to the death of an intimate family
      member or friend, inside the conceptual framework for nursing treatment and care.
      This project exposes bereavement in a fashion similar to that used by "NANDA" for
      its distinct diagnostic categories: title, definition and distinguishing
      characteristics. Furthermore, the authors include an evaluation guide which may
      facilitate making a diagnosis between normal and dysfunctional bereavement; the
      authors propose objectives and activities which a nurse can perform to help to
      complete the bereavement process in a healthy and adaptive manner. In order to
      deal with these situations, a consensus document may be useful; at the same time
      this can become a professional development aide which includes theoretical
      knowledge about bereavement, adroitness in relation to helpful measures and which
      facilitates a conscious awareness by health professionals regarding their own
      personal attitudes and difficulties in the face of death and bereavement.
      Adequate nursing care during the first phases of this process, which helps the
      individual or family to mobilize all their resources, may lead to a better
      evolution of this process and to a recuperation of the affective loss.

PMID- 14969204
TI  - [Nurse-woman communication. Choosing a permanent contraceptive method].
AB  - The article deals with the needs thirty women; residents in two favelas in the
      northeastern region of Brazil, manifested when they spoke about their lives and
      their feelings derived from their condition of being women as well as their
      relationship with the world; all of this is related to tying up their Fallopian
      tubes. This article describes the actions which nurses carried out based on the
      needs each of these patients manifested. Data were compiled by means of directly
      observing these patients, using interpersonal relationship techniques. This shows
      the importance of a humanistic attitude on behalf of nurses when dealing with a
      person who needs help.

PMID- 14969205
TI  - [Opiates. Analyzing the effects of opiates on the body and the nursing approach
      for opiate poisoning].

PMID- 14969206
TI  - [Guide for planning improvement areas].

PMID- 14969207
TI  - [A planet and a destiny].

PMID- 14969208
TI  - Biologically driven implant treatment.

PMID- 14969209
TI  - Realities and limitations in the management of the interdental papilla between
      implants: three case reports.
AB  - A predictable, aesthetic result is sometimes difficult to achieve when two or
      more adjacent implants are placed in the anterior maxilla. Maintenance of the
      distance from the interproximal crest of bone to the contact point influences the
      presence or absence of the interdental papilla. The design of the coronal portion
      of implants currently in the market and the contour of the implant-abutment
      junction may further affect the biology and reformation of the papilla between
      two adjacent implants. Through a series of case reports, parameters influencing
      implant placement are presented.

PMID- 14969210
TI  - Screening for hypertension: what role does the dental team play?

PMID- 14969211
TI  - The two-implant mandibular overdenture as first-choice treatment objective.

PMID- 14969212
TI  - Factors influencing marginal tissue remodeling around implants.

PMID- 14969213
TI  - Use of stereolithographic models as diagnostic and restorative aids for
      predictable immediate loading of implants.
AB  - Implant dentistry has evolved into one of the most predictable treatment
      alternatives in all of medical science. Advances in the surgical and prosthetic
      components, implant designs and surface technologies, and imaging techniques have
      allowed for significant modifications to occur with respect to one- and two-stage
      surgical protocols, accelerating treatment times to the benefit of patient and
      clinician. This article presents a technique to improve surgical and restorative
      accuracy, allowing for predictable placement and immediate loading of implants
      through use of CT imaging, stereolithographic models, and CT-derived surgical
      templates.

PMID- 14969214
TI  - Achieving case acceptance in older adult patients.

PMID- 14969215
TI  - Update to procedural hemostasis and sulcular fluid control.

PMID- 14969216
TI  - Immediate non-occlusal loading vs. early loading in partially edentulous
      patients.
AB  - Immediate loading of dental implants can reduce treatment time and management
      concerns, thus increasing patient acceptance. This paper reports the authors'
      preliminary experience with partially edentulous patients having received non
      occlusally loaded provisional restorations within 24 hours of surgery, compared
      to patients treated according to an early loading protocol. The present data
      suggest that implant supported fixed partial prostheses can be immediately non
      occlusally loaded and restored with a predictability similar to early loaded
      implants.

PMID- 14969217
TI  - Lasers in dentistry: soft tissue capabilities.

PMID- 14969218
TI  - Prototype provisional restorations for implant-supported, full-mouth, metal
      ceramic reconstructions: the hybrid technique.
AB  - The restoration of fully edentulous patients using fixed, metal-ceramic
      prostheses is one of the most challenging tasks in aesthetic dentistry.
      Provisional restorations provide the treatment team with a valuable means of
      addressing criteria that are required throughout the surgical, prosthetic, and
      technical stages. They also enable the clinician to place and evaluate a
      prototype of the definitive restoration in the patient's intraoral environment.
      This presentation describes a technique for the fabrication of provisional
      restorations for patients receiving fixed implant prostheses.

PMID- 14969219
TI  - Summary report of Kentucky Board of Nursing Advisory opinions on nursing practice
      issues.

PMID- 14969221
TI  - The effectiveness of alcohol based hand rubs and compliance with hand hygiene.
AB  - Pittet et al.'s (2000) study observed that an increase in compliance with hand
      hygiene, especially alcohol based hand rubs, was related to a decrease in the
      rate of nosocomial infections. The results of this study can be used in a group
      utilization project of providing information on efficacy and compliance issues
      related to hand hygiene. All HCWs, but most importantly nurses, can recommend
      hand hygiene programs on specific units to ensure client health and reduce
      unwanted health care cost. Feasibility issues would include teaching correct hand
      hygiene technique and compliance for new hospital employees and costs of
      educational materials. Considerations would be the length of program, location,
      and implementation strategies. Future research might focus on the use of a
      smaller sample size, where more control can be obtained, and the use of different
      hand hygiene techniques in the prevention of nosocomial infections.

PMID- 14969222
TI  - Sweet pain management in newborns.
AB  - Gradin et al.'s (2002) study supported the use of oral glucose to help relieve
      pain in neonates. The results of this study could be used to support a research
      utilization project to promote the use of oral glucose in nursing practice.
      Feasibility issues would include the need to educate nurses on how to incorporate
      this research in practice. Future research could be done to determine if glucose
      loses its effectiveness with increasing age or at what age would a different form
      of analgesic be more effective.

PMID- 14969223
TI  - Prescription drugs: recent trends in utilization, expenditures, and coverage.

PMID- 14969224
TI  - [Galen " On the anatomy of nerves": Translation from the Greek text and
      discussion].
AB  - Galen's treatise "On the Anatomy of Nerves" was translated literally from the
      Greek text (Kuhn's edition, vol. 2, pp. 831-856) into Japanese, utilizing the
      knowledge of anatomy. The previous Latin and English translations, as well as the
      descriptions of the nervous system in the other Galenic texts such as "Anatomical
      Procedures" and "On the Usefulness of the Parts of the Body," were utilized as
      references for the present translation, but it became evident from the present
      study that the previous translations contained an abundance of immature and
      erroneous understandings of the Galenic text. The present study has made it clear
      that the third cranial nerve referred to by Galen contains the most branches of
      the trigeminal nerve, and that the fourth cranial nerve represents the
      sympathetic trunk and the palatine nerves. The Galenic texts which were
      translated into Latin mainly in the 16th century before development of anatomical
      knowledge contain misunderstandings peculiar to the age. Thus the modern
      translations inherit some misunderstandings found in those Latin translations.
      Descriptions in the Galenic "On the Anatomy of Nerves" appear vague at first
      sight, but the described structures can be identified in most cases without doubt
      on the basic of anatomical knowledge. Furthermore we can estimate how Galen
      developed the preceding understanding of the nervous system made by Marinus on
      the basis of his own observations.

PMID- 14969225
TI  - [The surgical license of Otaguro Gentan and its background].
AB  - After the birth of Caspar-style surgery (kasuparu-ryu geka) during the 1650s, for
      about three decades, certificates issued by surgeons of the Dutch East India
      Company proved useful to those pursuing a career as a 'Western-style physician'.
      Five of these 'diploma' have survived the ravages of time. Four of the five
      beneficiaries are well known. An investigation in Northern Kyushu and Shikoku
      brought to light historical records that clarify the hitherto unknown background
      of the fifth one, Otaguro Gentan. Gentan was the second son of Otaguro Shozaemon,
      a village headman in the province of Chikugo. With no prospects of succeeding his
      father, he went to serve in the residence of Kuze Hiroyuki in Edo. This powerful
      imperial councillor suggested an education in Western surgery at the Dutch
      trading post in Nagasaki. The instruction given by Arnold Dircksz ceased in
      October 1668 when he issued a certificate. After his 'graduation', Otaguro went
      to Edo again where he was employed by Hachisuga Tsunamichi, the young ruler of
      Awa. He changed his name to Mizogami, and for generations the sons of his family
      served as physicians to the Hachisuga family. Gentan was treaed with great
      generosity by Tsunamichi and his successor Tsunanori. In 1694, he was even
      granted use of Tsunamori's personal ship to travel to Nagasaki for further
      medical studies. But Gentan soon fell ill and after a brief visit to the village
      of his ancestors, he died at the end of the same year.

PMID- 14969226
TI  - [The Tuberculosis outbreak due to whooping cough inoculation at Iwagasaki-machi
      in 1949].
AB  - Due to pertussis inoculation, 65 infants were accidentally infected by
      tuberculosis in Iwagasaki-machi, Miyagi Prefecture in 1949. The GHQ/SCAP record
      on Tuberculosis in Iwagasaki documented the details of this affair and the
      clinical reports about the victims, and they were the first to be treated by
      Streptomycine in Japan. The following three causes of mycobacterium tuberculosis
      contamination due to pertussis vaccine were considered, but no conclusive
      solution was decided. 1) Adulteration by manufacturer. 2) Carelessness of doctor.
      3) Adulteration by a third person for unknown reason. The Japanese official
      records do not provide extensive information about it, except for the medical
      articles of Kosankinkenkyuzasshi (Sendai). The parents of the 65 victims,
      including 2 dead infants, had accused the governmental official administrator of
      the responsibility for reparation of the accidental inoculation, but they dropped
      the case against the government 5 years later. There is no detailed record about
      the judicial aspects of this incident.

PMID- 14969227
TI  - [Pedro Lain Entralgo, medico-historian and thinker].

PMID- 14969228
TI  - Care of the mentally disabled in and around Edinburgh c.1680 - c.1820.

PMID- 14969229
TI  - David livingstone and southern africa's first recorded cases of sickle-cell
      anaemia?

PMID- 14969230
TI  - Dr William Bruce (1835-1920), the scottish highland spa at strathpeffer; and a
      possible description of polymyalgia rheumatica.

PMID- 14969231
TI  - Medieval hospitals in Scotland: A cure for body or soul?

PMID- 14969232
TI  - Robert Knox and Joseph Lister: pioneers of vascular physiology.

PMID- 14969233
TI  - The case of madeleine smith: a victorian discourse of desire and death.

PMID- 14969234
TI  - The Royal Medical Society's library.

PMID- 14969235
TI  - Torphichen and the knights hospitaller.

PMID- 14969236
TI  - [Philipp Phoebus (1804-1880): his life and scientific work].

PMID- 14969237
TI  - [The indivisibility of the ownership and the running of pharmacy].
AB  - The indivisibility of the ownership and the running of a pharmacy is one of the
      basic principles of the pharmaceutical profession and find its origin in two
      ancient texts: The Royal Declaration of April 25th, 1777 and some twenty-six
      years later, the well-know law of 21st Germinal, year XI. The spirit of the law
      should have done with the competitors, but it did not. The principle was
      stretched many times until a Court Decision in June 23rd, 1859. Since then the
      rule was progressively confirmed and many conventions relative to the ownership
      and the running have been forbidden. Yet certain derogations do exist.
      Nevertheless, the publication of a law in December 11th, 2001, called " law
      MURCEF" overthrows deeply the principle because it could allow for
      reconsideration.

PMID- 14969238
TI  - [The history of polio in Brazil and its control through immunization].
AB  - The article analyzes the scientific and political discussions and activities
      surrounding the problem of polio in Brazil during the twentieth century. It
      examines the issues that shaped disease control policy and led to the 1980
      introduction of National Vaccination Days.

PMID- 14969239
TI  - Gates Foundation gives 27 million US dollars to fight Japanese encephalitis.

PMID- 14969240
TI  - New Indian centre to boost brain research and training.

PMID- 14969241
TI  - [What physicians see and don't see--moral perception of the physician-patient
      relations].

PMID- 14969242
TI  - [From a sick physician to a difficult patient].

PMID- 14969243
TI  - [Discussion of article: Detection of chlamydial particles using direct
      immunofluorescence in ambulatory ophthalmologic practice].

PMID- 14969244
TI  - Finance issue brief: mandated benefits: prostate cancer screening coverage
      requirements: year end report-2003.

PMID- 14969245
TI  - Finance issue brief: mandated benefits: cervical cancer screening coverage
      requirements: year end report-2003.

PMID- 14969246
TI  - Consumer-driven health care:  implications for providers, payers, and policy
      makers.

PMID- 14969247
TI  - RCN launch guidance for nurses on the integration of complementary therapies into
      clinical practice at annual conference.

PMID- 14969248
TI  - Finance issue brief: high-risk pools: coverage for the uninsurable: year end
      report-2003.

PMID- 14969249
TI  - Chemist opticians.

PMID- 14969251
TI  - The first state-run pharmacy in 19th-century Serbia.

PMID- 14969250
TI  - [Vitamins and trace elements. Franco-Moroccan Congress. Rabat, 28-31 October
      2002. Abstracts].

PMID- 14969252
TI  - Elephants' milk.

PMID- 14969253
TI  - [On the artful, yet pernicious body. A cultural-historical interpretation of
      Bidloo's anatomical atlas].
AB  - Among historians of science and medicine it is well known that early modern
      anatomical representations, in addition to illustrating ideas on the body, also
      teach a moral lesson. The anatomical cabinets of Frederik Ruysch (1638-1731) are
      exemplary. His exhibits show 1) the divine design of the body and 2) the
      fragility of life and man's dependence on God for his existence. Govard Bidloo
      (1649-1713), in his anatomical atlas, the Anatomia humani corporis (1685), does
      not seem to answer this standard view on the 'moral teaching' of anatomy. It has
      been argued that his depictions of dead and mutilated (parts of) bodies indicate
      a more realistic way of representation, devoid of metaphor and morality. Yet,
      taking the fierce controversy between Bidloo and Ruysch as my starting point, I
      show that in fact there is a moral lesson in Bidloo's anatomy. It reflects two
      important aspects of Bidloo's Mennonite faith, i.e. the aversion against
      beautiful decoration and the fascination with suffering and death found in martyr
      stories.

PMID- 14969254
TI  - Medicaid and indigent care issue brief: Medicaid: benefits and services: year end
      report-2003.
AB  - Medicaid provides health care insurance for low-income children, some parents who
      meet income thresholds, pregnant women, the elderly and the disabled. In order to
      receive federal funds for Medicaid, each state must offer coverage for the
      following health care services: inpatient and outpatient hospital services;
      physician services; medical and surgical dental services; nursing facility
      services; home health care services; family planning services; rural health
      clinic services; laboratory and x-ray services; pediatric and family nurse
      practitioner services; federally qualified health center services; nurse-midwife
      services; and early and periodic screening, diagnosis and treatment (EPSDT)
      services for individuals under age 21. States can also choose to cover certain
      additional services under their Medicaid plans, and these often include
      prescription drugs, dental services (nonmedical or surgical), clinic services,
      and vision and hearing services. It is up to each state to decide what optional
      services to include with the mandated services to create their Medicaid benefit
      package.

PMID- 14969255
TI  - Providers issue brief: physical education: year end report-2003.

PMID- 14969256
TI  - Medicaid and indigent care issue brief: Medicaid: provider reimbursement: year
      end report-2003.
AB  - Medicaid provider reimbursement rates have been a hot topic for the last several
      years. Thirty states, including California, Hawaii, Indiana, Maryland,
      Mississippi, New York and Wisconsin, addressed the issue in the 2001 legislative
      session while 33 states enacted legislation dealing with provider reimbursement
      in 2002.

PMID- 14969257
TI  - Medicaid and indigent care issue brief: Medicaid: eligibility: year end report
      2003.
AB  - Medicaid provides health insurance coverage to low-income children, parents
      meeting specific income thresholds, pregnant women, the elderly and people with
      disabilities. In 1999, Medicaid provided health care insurance to approximately
      32 million low-income Americans. However, in that same year, 42 million Americans
      had no health insurance at all. In order to reduce the number of people without
      health insurance, states have expanded or clarified their eligibility standards
      to allow more people to enroll in Medicaid and other medical assistance programs.

PMID- 14969258
TI  - Providers issue brief: scope of practice and prescriptive authority: year end
      report-2003.
AB  - Nonphysician providers continue to achieve enhanced stature, in part by gaining
      more autonomy in prescribing drugs. There is growing support for the concept that
      the public health is best served by the broadest access to primary care along
      with the safe use of pharmaceuticals. The states continue in their efforts to
      find ways to promote the use of less specialized and less costly providers to
      help serve the ever-growing population who have access to health care services.

PMID- 14969259
TI  - Pharmaceuticals issue brief: managed care drug formularies: year end report-2003.
AB  - A number of states regulate the use of drug formularies by requiring MCOs and
      HMOs to disclose drugs listed on the plan formulary or to disclose procedures to
      obtain drugs that are not listed on the formulary.

PMID- 14969260
TI  - Providers issue brief: nursing home staffing standards: year end report-2003.
AB  - For more than a decade, lawmakers have focused on improving care in the nation's
      nursing homes by mandating tighter regulations for the industry. With a growing
      elderly population and findings that suggest a majority of nursing facilities are
      understaffed to the point of endangering the health of patients, states and the
      federal government are strengthening their resolve to crack down on delinquent
      facilities and introduce minimum requirements for staffing levels to improve
      quality of care. A common way states have chosen to impose these requirements is
      through minimum staff-to-patient ratios, but states also must address how to fund
      mandated staff increases.

PMID- 14969261
TI  - Providers issue brief: Medical malpractice: tort reform: year end report-2003.
AB  - Many questions exist surrounding the origins of the escalating cost of medical
      malpractice coverage. Insurers and health providers claim excessive litigation
      and overly generous jury awards have hardened the market. The American Trial
      Lawyers Association and consumer advocacy groups claim insurance premium rates
      have not tracked medical inflation or the payouts of jury awards over the last 30
      years. State efforts have been hampered by the lack of conclusive data as to the
      cause . However, the potential impact is very clear, limited health care access
      as result of a loss in the health care workforce.

PMID- 14969262
TI  - Finance issue brief: any willing provider: year end report-2003.
AB  - Today, almost half the states have laws obligating managed care organizations
      (MCOs) such as health maintenance organizations (HMOs) and preferred provider
      organizations (PPOs) to contract with any willing health care provider. Although
      most provisions are limited to pharmacies or pharmacists, several states have
      adopted broad provisions applying to hospitals, physicians, chiropractors,
      pharmacists, podiatrists, therapists and nurses.

PMID- 14969263
TI  - Finance issue brief: direct access: year end report-2003.
AB  - Consumer demand for a less restrictive referral system has urged legislators, as
      well as the managed care industry and those in the medical field, to seek the
      best solution to the problem. The point of service (POS) plan was an early
      attempt by managed care plans to provide more freedom for enrollees. But POS
      plans are not always available or cost effective. Several of the larger managed
      care organizations, in an effort to improve enrollee and provider satisfaction,
      have eliminated or streamlined their referral processes. The American Medical
      Association has recommended that primary care and other medical specialty
      organizations collaborate in developing guidelines for specialty referrals,
      urging health plans to allow direct access in network without financial penalty
      as long as the access conforms with the established guidelines. In the meantime,
      legislators have responded to constituents by enacting measures that mandate
      direct access for specific types of care or standing referrals for ongoing
      treatment.

PMID- 14969264
TI  - [Current thought on hereditary transmission and human genetics].
AB  - On the basis of a review of the historiography on thought about hereditary
      transmission and human genetics in the 20th century in Britain, the United
      States, Germany, Russia, Sweden, and the Netherlands, a new research perspective
      is formulated. Concepts of heredity and their use in society have been various
      and diverse. Definitions of heredity and of the influence of 'nature' and
      'nurture' in shaping genetic material have significantly changed. In the new
      research perspective the focus is directed to the role of a broad range of
      concepts of heredity in framing debates and practices around health, disease, and
      behaviour, including but not exclusively the concepts of Mendelian genetics, neo
      Lamarckism', and concepts prevalent in eugenic movements. A research programme is
      outlined that is directed at specific problem fields in health care (e.g.
      alcoholism), and uses various sources to examine the historical dynamics in
      medical and public spheres.

PMID- 14969265
TI  - Providers issue brief: automated external defibrillators: year end report-2003.

PMID- 14969266
TI  - Special issue: Papers from the NATO Advanced Research Workshop on Thiol
      Metabolism and Redox Regulation. April 10-13, 2002, Pisa, Italy.

PMID- 14969267
TI  - Finance issue brief: comprehensive consumer rights bill: year end report-2003.
AB  - The health care industry has historically used established formats for patient
      rights in order to maintain the integrity and quality of care in all settings of
      care provision. By establishing rights and responsibilities for patients, it
      increased patient involvement and created boundaries for acceptable practice for
      health care providers. As the provision of health care is evolving and including
      the health payor as never before, legislators are faced with the task of bridging
      the gap for consumers by creating protective measures that are referred to as a
      "Patient's Bill of Rights".

PMID- 14969268
TI  - Finance issue brief: Consumer grievance procedures: internal and independent
      appeals: year end report-2003.

PMID- 14969269
TI  - Finance issue brief: bans on financial incentives: year end report-2003.

PMID- 14969270
TI  - Providers issue brief: family caregiving: year end report-2003.
AB  - In response to the national Family Caregiver Support Program, created in the
      Older Americans Act of 2000, states have implemented or expanded programs to
      assist family and informal caregivers in providing care to frail and disabled
      individuals. As long-term care costs continue to rise, states are looking to help
      people who care for elderly individuals by keeping them off Medicaid and out of
      costly nursing homes.

PMID- 14969271
TI  - Providers issue brief: tobacco: public place smoking: year end report-2003.

PMID- 14969272
TI  - [The motion machine of Samuel Theodor Quellmalz].
AB  - In 1735 the physician Samuel Theodor Quellmalz invented a machine which imitated
      the movements of a horse and was designed for medical treatment as well as
      general fitness. The invention paradigmaticlly characterizes the dominant medical
      discourse of that time and demonstrates a new confidence in technical innovations

PMID- 14969273
TI  - [Is the detection of microdeletions of the Y chromosome necessary before ICSI?
      Against the systematic testing of microdeletions of the Y chromosome in infertile
      men before assisted reproduction procedures].

PMID- 14969274
TI  - Medicare program; establishment of the Medicare Coverage Advisory Committee and
      request for nominations for members. Notice.
AB  - This notice announces the establishment of the Medicare Coverage Advisory
      Committee that will advise the Secretary of Health and Human Services and the
      Administrator of the Health Care Financing Administration, as requested by the
      Secretary, whether medical items and services are reasonable and necessary under
      title XVIII of the Social Security Act. This notice requests nominations for
      members for the Committee. This notice also announces the signing by the
      Secretary on November 24, 1998 of the charter establishing the Committee. This
      charter ends at close of business on November 23, 2000 unless renewed by the
      Secretary.

PMID- 14969275
TI  - Death anxiety as a predictor of posttraumatic stress levels among individuals
      with spinal cord injuries.
AB  - Because the onset of a spinal cord injury may involve a brush with death and
      because serious injury and disability can act as a reminder of death, death
      anxiety was examined as a predictor of posttraumatic stress levels among
      individuals with disabilities. This cross-sectional study used multiple
      regression and multivariate multiple regression to examine whether death denial
      and death awareness predicted posttraumatic stress disorder (PTSD) among veterans
      and civilians with spinal cord injuries (N = 313). The results indicated that
      death anxiety (after controlling for demographic and disability-related
      variables) predicted a significant amount of the total levels of posttraumatic
      stress reactions among individuals with spinal cord injuries. Further, death
      awareness, pain level, and spiritual/religious coping significantly predicted the
      posttraumatic stress clusters of reexperiencing, avoidance, and hyperarousal.
      Death denial significantly predicted only hyperarousal. Because death anxiety
      predicts various aspects of PTSD reactions, one possible therapeutic implication
      is that addressing death-related topics may help to reduce PTSD reactions.
      Further research is needed to better ascertain the possible causality among these
      variables.

PMID- 14969276
TI  - Comparative study of suicide potential among Pakistani and American psychiatric
      patients.
AB  - This study compared suicide potential and suicide attempts in 50 Pakistani and 50
      American psychiatric patients all of whom reported a positive history of suicide
      attempts during the past 1-5 years. It further explored the role of nationality,
      gender, diagnosis, and marital status in respondents' potential for suicide and
      suicide attempts. The American sample reported a higher degree of suicide
      potential on the Firestone Assessment of Self-Destructive Thoughts (FAST), more
      suicide attempts, and a larger number of suicide precipitants (family conflicts,
      work pressure, wish for death, loneliness, financial problems, and mental
      disorders/drug withdrawal) than did the Pakistani sample. For suicide attempts,
      effects of 3-way interaction for gender, marital status and nationality were
      found significant. However, these effects were non-significant for respondent's
      potential for suicide. In addition, the FAST was found to have a significantly
      high correlation with suicide attempts. Thus, it may be inferred that the FAST
      can be used as a valuable screening instrument for the identification of patients
      at risk for suicide in diverse cultural settings. However, more prospective
      validity studies are needed to enhance our cross-cultural understanding of
      suicide; identification of psychiatric patients at risk for suicide by the FAST;
      and for effective treatment and prevention programs for Eastern and Western
      societies.

PMID- 14969277
TI  - Response to Leask and McIntyre's attack on myself as a public opponent of
      vaccination.

PMID- 14969278
TI  - The use of death metaphors to understand personal meaning of death among Hong
      Kong Chinese undergraduates.
AB  - Many Chinese words are pictographic in nature and Chinese people often tend to
      use metaphorical expressions to communicate emotional feelings. The assessment of
      death images and metaphors provides a meaningful way of understanding personal
      perceptions of death among the Chinese. The purpose of this study was to
      establish an instrument to assess the death metaphors of Hong Kong Chinese for
      assessment and empirical research. Thirty death metaphor statements in Chinese
      were created from items of the Revised Death Fantasy Scale (RDFS; J. McLennan &
      C. A. Stewart, 1997) and a previous pilot study in Hong Kong (S. M. Y. Ho, 2001).
      The item pool was administered to 100 undergraduates together with the Templer's
      Death Anxiety Scale. Seven out of the 10 highest scored death metaphor statements
      were from the items that had been created for this study. Descriptive statistics
      of individual items suggested an interpersonal dimension of death perception that
      is not emphasized in Western literature. Factor analysis generated a 18-item
      Death Metaphors Scale (DMS) with 2 9-item subscales: the Positive Metaphors (f =
      .85) and the Negative Metaphors (f = .81). The scores of DMS subscales are
      significantly correlated with the Templer's Death Anxiety Scale but not with
      corresponding scores of the RDFS. The DMS was considered a potentially useful
      instrument to study death metaphors among Chinese.

PMID- 14969279
TI  - Finding boundaries inside prison walls: case study of a terminally ill inmate.
AB  - The number of terminally ill prison inmates rises each year. Mental health
      professionals are uniquely prepared to provide therapy during the end-of-life
      process with their assessment, training, empathy, and communication skills. This
      case study examines the six-month therapy of one terminally ill inmate, using a
      client-centered approach. Drawing from existential therapy, the review of
      meaningful life events in the client's life clarifies current goals and the value
      of the current final stage of life. Ethical issues that arose are discussed,
      including pain management and compassionate release. Creative solutions to these
      ethical dilemmas were implemented through consideration of the overt and
      underlying goals of the inmate, the necessary rules and protocols of the prison,
      and in conjunction with professional codes of ethics.

PMID- 14969280
TI  - Part I. Chromatography using ultra-stable metal oxide-based stationary phases for
      HPLC.
AB  - The first part of the review contrasts the main drawbacks of silica-based
      packings such as their relative thermal and chemical instability with excellent
      stability of metal oxides. The paper concerns mainly ZrO2, TiO2 and Al2O3.
      Methods of preparation of spherical particles for HPLC are described. Surface
      chemistry of the oxides is, however, very different from that of silica. Ability
      of the oxides to ion- and ligand exchange is discussed from a chromatographic
      point of view.

PMID- 14969281
TI  - Part II. Chromatography using ultra-stable metal oxide-based stationary phases
      for HPLC.
AB  - In this part of the review authors discuss methods used for modification of metal
      oxide surfaces. On the basis of literature data it is shown, that silanization of
      the surfaces do not form stable supports for chromatography. On the other hand,
      the success of polymer modified surfaces such as polybutadiene (PBD) and
      polystyrene (PS) is emphasized. Permanent modification of metal oxide surfaces
      with Lewis bases is also widely discussed. Chromatographic properties of polymer
      modified surfaces of zirconia are discussed in details. The perspectives of
      carbon-coated metal oxide surfaces in HPLC and high temperature separations are
      described.

PMID- 14969282
TI  - Applicability of headspace solid-phase microextraction to the determination of
      multi-class pesticides in waters.
AB  - The applicability of headspace solid-phase microextraction (HS-SPME) to pesticide
      determination in water samples was demonstrated by evaluating the effects of
      temperature on the extraction of the pesticides. The evaluations were performed
      using an automated system with a heating module. The 174 pesticides that are
      detectable with gas chromatograph were selected objectively and impartially based
      on their physical properties: vapor pressure and partition coefficient between
      octanol and water. Of the 174 pesticides, 158 (90% of tested) were extracted with
      a polyacrylate-coated fiber between 30 and 100 degrees C and were determined with
      gas chromatograph-mass spectrometry. The extraction-temperature profiles of the
      158 extracted pesticides were obtained to evaluate the effects of temperature on
      the extraction of pesticides. The pesticides were classified into four groups
      according to the shape of their extraction-temperature profiles. The line of
      demarcation between extractable pesticides and non-extractable pesticides could
      be drawn in the physical property diagram (a double logarithmic plot of their
      vapor pressure and partition coefficient between octanol and water). The plot
      also revealed relationships between classified extraction features and their
      physical properties. The new method for multi residue screening in which the
      analytes were categorized into sub-groups based on extraction temperature was
      developed. In order to evaluate the quantitivity of the developed method, the 45
      pesticides were chosen among the pesticides that are typically monitored in
      waters. Linear response data for 40 of the 45 was obtained in the concentration
      range below 5 microg/l with correlation coefficients ranging between 0.979 and
      0.999. The other five pesticides had poor responses. Relative standard deviations
      at the concentration of the lowest standard solution for each calibration curve
      of the pesticides ranged from 3.6 to 18%. The value of 0.01 microg/l in the
      limits of detection for 17 pesticides was achieved only under the approximate
      conditions for screening, not under the individually optimized conditions for
      each pesticide. Recoveries of tested pesticides in actual matrices were
      essentially in agreement with those obtained by solid-phase extraction.

PMID- 14969283
TI  - Physical origin of peak tailing on C18-bonded silica in reversed-phase liquid
      chromatography.
AB  - Single component isotherm data of caffeine and phenol were acquired on two
      different stationary phases for RPLC, using a methanol/water solution (25%, v/v,
      methanol) as the mobile phase. The columns were the non-endcapped Waters Resolve
      C18, and the Waters XTerra MS C18. Both columns exhibit similar C18 -chain
      densities (2.45 and 2.50 micromol/m2) and differ essentially by the nature of the
      underivatized solid support (a conventional, highly polar silica made from water
      glass, hence containing metal impurities, versus a silica-methylsilane hybrid
      surface with a lower density of less acidic free silanols). Thirty-two adsorption
      data points were acquired by FA, for caffeine, between 10(-3) and 24 g/l, a
      dynamic range of 24,000. Twenty-eigth adsorption data points were acquired for
      phenol, from 0.025 to 75 g/l, a dynamic range of 3000. The expectation
      maximization procedure was used to derive the affinity energy distribution (AED)
      from the raw FA data points, assuming a local Langmuir isotherm. For caffeine,
      the AEDs converge to a bimodal and a quadrimodal distribution on XTerra MS-C18
      and Resolve-C18, respectively. The values of the saturation capacity (q(s,1)
      approximately equal to 0.80 mol/l and q(s,2) approximately equal to 0.10 mol/l)
      and the adsorption constant (b1 approximately equal to 3.11/mol and b2
      approximately equal to 29.1 l/mol) measured on the two columns for the lowest two
      energy modes 1 and 2, are comparable. These data are consistent with those
      previously measured on an endcapped Kromasil-C18 in a 30/70 (v/v), methanol/water
      solution (q(s,1) = 0.9 mol/l and q(s,2) = 0.10 mol/l, b1 = 2.4 l/mol and b2 =
      16.1 l/mol). The presence of two higher energy modes on the Waters Resolve-C18
      column (q(s,3) approximately equal to 0.013 mol/l and q(s,4) approximately equal
      to 2.6 10(-4) mol/l, b3 approximately equal to 252 l/mol and b4 = 13,200 l/mol)
      and the strong peak tailing of caffeine are explained by the existence of
      adsorption sites buried inside the C18-bonded layer. It is demonstrated that
      strong interactions between caffeine and the water protected bare silica surface
      cannot explain these high-energy sites because the retention of caffeine on an
      underivatized Resolve silica column is almost zero. Possible hydrogen-bond
      interactions between caffeine and the non-protected isolated silanol groups
      remaining after synthesis amidst the C18-chain network cannot explain these high
      energy interactions because, then, the smaller phenol molecule should exhibit
      similarly strong interactions with these isolated silanols on the same Resolve
      C18 column and, yet, the consequences of such interactions are not observed.
      These sites are more consistent with the heterogeneity of the local structure of
      the C18-bonded layer. Regarding the adsorption of phenol, no matter whether the
      column is endcapped or not, its molecular interactions with the bare silica were
      negligible. For both columns, the best adsorption isotherm was the Bilangmuir
      model (with q(s,1) approximately equal to 2 and q(s,2) approximately equal to
      0.67 mol/l, b1 0.61 and b2 approximately equal to 10.3 l/mol). These parameters
      are consistent with those measured previously on an endcapped Kromasil-C18 column
      under the same conditions (q(s,1) = 1.5 and q(s,2) = 0.71 mol/l, b1 = 1.4 l/mol
      and b2 = 11.3 l/mol). As for caffeine, the high-energy sites are definitely
      located within the C18-bonded layer, not on the bare surface of the adsorbent.

PMID- 14969284
TI  - Temporally convoluted Gaussian equations for chromatographic peaks.
AB  - Both spatial and temporal peaks that are produced by the discrete parcel model
      can be mathematically approximated by Gaussian functions, but the transformation
      from a spatial pattern to a temporal image requires a convolution treatment. A
      first-order convolution is given for temporal peaks under a linear isotherm,
      whereas a second-order convolution is proposed for those under non-linear
      isotherms. Numerical tests show that the peak shapes generated by the proposed
      temporally convoluted Gaussian equations (TCG) match perfectly with those
      obtained by the discrete parcel model. Although the full TCG equation may be
      quite complicated, it can be made easier by a recursion calculation technique,
      and a group of peak curves can be plotted simultaneously on computer worksheet.
      The results also suggest that the temporal distortion effect should be
      predominately considered, in addition to those known-to-exist spatial effects,
      for explaining the peak asymmetry.

PMID- 14969285
TI  - Heterogeneity of the surface energy on unused C18-chromolith adsorbents in
      reversed-phase liquid chromatography.
AB  - Single-component adsorption isotherm data were acquired by frontal analysis (FA)
      for phenol and caffeine on a new C18-Chromolith column (Merck, Darmstadt,
      Germany), using a water-rich mobile phase (methanol/water, 15/85, v/v). These
      data were modeled for best agreement between the experimental data points and the
      adsorption isotherm model. The adsorption-energy distributions, based on the
      expectation-maximization (EM) procedure, were also derived and used for the
      selection of the best isotherm model. The adsorption energy distributions (AEDs)
      for phenol and caffeine converged toward a trimodal and a quadrimodal
      distribution, respectively. Energy distributions with more than two modes had not
      been reported before for the adsorption of these compounds on packed columns. The
      third high energy mode observed for both phenol and caffeine seems to be specific
      of the surface of the monolithic column while the first and second low energy
      modes have the same physical origin as the two modes detected on packed columns.
      These results suggest significant differences between the structures of the
      porous silica in these different materials.

PMID- 14969286
TI  - Band splitting in overloaded isocratic elution chromatography III. Modeling of
      adsorbate-adsorbate interactions by a two-component extension of a BET kinetic
      isotherm model.
AB  - A new two-component competitive adsorption model was derived to account for the
      competitive adsorption data of mixtures of ethylbenzoate and 4-tert-butylphenol,
      on a C18-Kromasil column under RPLC conditions (mobile phase, methanol/water,
      62/38, v/v). The derivation is based on kinetic arguments and is an extension to
      multicomponent systems of the single-component BET isotherm. The model assumes
      that the molecules of the first compound (A) can adsorb on layers made of
      molecules of either A or B, while molecules of B can only adsorb on layers made
      of molecules of A. This makes the competitive isotherm consistent with the single
      component isotherms of ethylbenzoate and 4-tert-butylphenol, the multilayer BET
      and the monolayer Langmuir isotherm models, respectively. The competitive
      adsorption data were acquired by frontal analysis (FA) with equimolar mixtures of
      eight different concentrations. For the seven lowest concentrations, these data
      were derived from the retention times of the shocks of the two compounds and the
      concentration of the intermediate plateau of the less retained compound. At the
      highest concentration (25 g/l), the individual band profiles were measured by
      collecting and analyzing twenty fractions. The low concentration data (C < or =
      10 g/l) are well accounted for by the two competitive isotherm models derived
      previously but these models fail to describe the experimental data of 4-tert
      butylphenol at high concentrations. By contrast, the new model predicts very well
      the experimental adsorption data for mixtures of ethylbenzoate and 4-tert
      butylphenol in the whole range of concentration studied. Our results suggest that
      the adsorption constant of 4-tert-butylphenol onto layers made of ethylbenzoate
      (b(B,A) = 0.0120 l/g) is intermediate between those of ethylbenzoate on layers
      made of 4-tert-butylphenol (b(A,B) = 0.0105 l/g) and of ethylbenzoate on itself
      (b(A,A) = 0.0145 l/g). This new model should give an improved description of the
      band splitting observed for 4-tert-butylphenol in the presence of ethylbenzoate.

PMID- 14969287
TI  - Hydrophobic and cation exchange mechanisms in the retention of basic compounds in
      a polymeric column.
AB  - A cation exchange retention mechanism concomitant with the well-known hydrophobic
      partition mechanism in a polymeric column has been observed and investigated.
      This exchange process is attributed to ionization of some acidic sites present in
      the polymer column at basic mobile phase pH values. Several drugs of different
      basicity have been chromatographed on a polymeric PLRP-S column with methanol
      water and acetonitrile-water mobile phases. The cation exchange between the
      protonated basic drug and the buffer cations (Na+, K+ and BuNH4+) is observed at
      the pH range where the protonated drug and the ionized sites of the column
      coexist. This process produces a shift of the retention versus pH plot of the
      base to pH values lower than those expected from the pKa of the base as well as a
      maximum in the plot at basic pH values. These effects are more pronounced for
      acetonitrile-water mobile phases.

PMID- 14969288
TI  - Protein separation with surfactant-coated polystyrene involving Cibacron Blue 3GA
      conjugated triton X-100.
AB  - Through mixing of porous polystyrene particles (Amberlite XAD-4), non-ionic
      surfactants, and surfactant-conjugated substrates (affinity ligand) in an aqueous
      solution led to the formation of a novel medium (affinity admicelle) for protein
      separation. The ligand (CB-Triton) was synthesized by mixing a triazine dye
      (Cibacron Blue 3GA (CB)) and a polyoxyethylene-type non-ionic surfactant (Triton
      X-100) in weakly alkaline solutions. Triton X-100 and CB-Triton were
      competitively sorbed onto XAD-4. Albumin (bovine serum), alcohol dehydrogenase
      (yeast), and lysozyme (chicken egg) having specific interaction to CB were
      collected onto the affinity admicelle. On the other hand, the collection of
      ovalubmin (chicken egg white), having no binding ability to CB, was negligibly
      small. Lysozyme in 100 microl of chicken egg white, diluted with 900 microl of 10
      mM Tris-HCl (pH 7.4), was successfully collected on 18 mg of CB-Triton admicelles
      and, then, it was eluted with 1 ml of aqueous solution of 100 mM phosphate (pH
      7.4). The recovery based on the activity for the lysis of micrococcus and the
      concentration factor were 60% and 40 (n = 3), respectively.

PMID- 14969289
TI  - Analysis of cyanobacterial toxins by hydrophilic interaction liquid
      chromatography-mass spectrometry.
AB  - The combination of hydrophilic interaction liquid chromatography with
      electrospray mass spectrometry (HILIC-MS) has been investigated as a tool for the
      analysis of assorted toxins produced by cyanobacteria. Toxins examined included
      saxitoxin and its various analogues (1-18), anatoxin-a (ATX-a, 19),
      cylindrospermopsin (CYN, 20), deoxycylindrospermopsin (doCYN, 21), and
      microcystins-LR (22) and -RR (23). The saxitoxins could be unequivocally detected
      in one isocratic analysis using a TSK gel Amide-80 column eluted with 65% B,
      where eluent A is water and B is a 95% acetonitrile/water solution, both
      containing 2.0 mM ammonium formate and 3.6 mM formic acid. The analysis of ATX-a,
      CYN and doCYN required 75% B isocratic. Simultaneous determination of 1-21 was
      also possible by using gradient elution. HILIC proved to be suitable for the
      analysis of microcystins, but peak shape was not symmetric and it was concluded
      that these compounds are best analysed using existing reversed-phase methods. The
      HILIC-MS method was applied to the analysis of field and cultured samples of
      Anabaena circinalis and Cylindrospermopsis raciborskii. In general, the method
      proved quite robust with similar results obtained in two different laboratories
      using different instrumentation.

PMID- 14969290
TI  - Nonaqueous capillary electrophoresis using a titania-coated capillary.
AB  - In this work, an ordered mesoporous titania film was introduced to coat a
      capillary by means of the sol-gel technique. Its electroosmotic flow (EOF)
      property was investigated in a variety of nonaqueous media (methanol, formamide
      and N,N'-dimethylformamide and mixtures of methanol and acetonitrile). The
      titania-coated capillary exhibited a distinctive EOF behavior, the direction and
      magnitude of which were strongly dependent on various parameters such as the
      solvent composition, apparent pH (pH*) and the electrolytes. The nonaqueous
      capillary electrophoresis separation of several alkaloids was investigated in the
      positively charged titania-coated capillary. Comparison of separation between
      coated and uncoated capillaries under optimal nonaqueous conditions was also
      carried out.

PMID- 14969291
TI  - Preparative isolation and purification of celastrol from Celastrus orbiculatus
      Thunb. by a new counter-current chromatography method with an upright coil planet
      centrifuge.
AB  - A new counter-current chromatography (CCC) method with an upright coil planet
      centrifuge, which holds four identical multilayer coil columns in the symmetrical
      positions around the centrifuge axis, was applied to the isolation and
      purification of celastrol from the roots of Celastrus orbiculatus Thunb. The
      crude celastrol was obtained by elution with light petroleum from ethanol
      extracts using 15 cm x 5 cm i.d. silica gel flash chromatography. Preparative CCC
      with a two-phase system composed of light petroleum (bp 60-90 degrees C)-ethyl
      acetate-tetrachloromethane-methanol-water (1:1:8:6:1, v/v) was successfully
      performed, yielding 798 mg celastrol at 99.5% purity from 1020 mg of the crude
      sample in one step separation.

PMID- 14969292
TI  - Application of shielded column liquid chromatography for determination of
      sulfamonomethoxine, sulfadimethoxine, and their N4-acetyl metabolites in milk.
AB  - A hazardous-chemical free method for simultaneous determination of
      sulfamonomethoxine (SMM), sulfadimethoxine (SDM), and their N4-acetyl metabolites
      in raw milk using shielded column liquid chromatography is developed. The target
      analytes are extracted by mixing with ethanol-acetic acid (97:3, v/v) followed by
      centrifugation. The procedure uses a Hisep shielded hydrophobic phase (SHP)
      column, isocratic elution with 0.1% acetic acid solution (pH 3.1, in water)
      ethanol (75:25, v/v), and a photo-diode array detector. Average recoveries from
      samples spiked at 25-500 ng/ml for each drug were >81% with relative standard
      deviations within 5%. The limits of quantitation were <25 ng/ml.

PMID- 14969293
TI  - [Within the foundation of the Rome Institute of Experimental Hygiene in the year
      1885: the climate of Rome].
AB  - To celebrate Prof.rs Vittorio Del Vecchio and Salvatore Ugo D'Arca, respectively
      the sixth and the seventh director of the Institute of Hygiene of the University
      of Rome, the Authors present and discuss the conferences on The climate of Rome
      given by Prof. Corrado Tommasi-Crudeli, founder and first director of such an
      Institute back in 1885. Particularly, the Authors illustrate the six tables shown
      by the speaker, which represent the scientific basis for the reclamation of Roman
      "Agro", affected by malaria at that time.

PMID- 14969294
TI  - [The District: the place of management of community health services or the place
      of governance of primary health care? The epidemiologic context].
AB  - This is a review of epidemiologic requirements for the governance of District
      health services. The governance concern both the health system (organization,
      management and assessment of health services) and the population's health (health
      needs, health services needs, determinants of health).

PMID- 14969295
TI  - [Is the patient's charter a tool for the implementation of health policies
      promoting health care quality? Results of a survey on Italian local health units
      over the period 1995-98].
AB  - Patient's Charter was introduced in Italy in the last decade with the aim of
      increasing community participation to the quality of health care. The Charter
      with reference to primary care services, should include information about the
      admission and standards of service that people can expect to receive. The purpose
      of the study was to assess, on the basis of a series of indicators, the presence
      of differences among different organisational model of Local Health Unit
      Districts. As regards Prevention Department, the association between quality
      indicators and geographic location was studied. We evaluated 112 Charters, 49.3%
      on the total amount of Italian Local Health Unit (LHU) that were issued during
      the period 1996-1998, using a data form with multiple choice questions. 104 out
      of 112 Charters showed quality items for Districts and Prevention Departments.
      Significant differences among the different groups of district organization model
      were shown for three indicators (waiting time, administrative details and chief
      in charge) respectively in General Practitioner area and in Psychiatric one. As
      regards Prevention Departments, no association was shown between geographic area
      and frequency of quality indicators, although a trend of higher frequence was
      found in Northern Area versus Central Area and Southern one. This study
      emphasizes the fact that data drawn from Patient's Charter can show the impact of
      different organisational and geographic conditions on quality of healthcare.

PMID- 14969296
TI  - [The quality of medical records: a retrospective study in Lazio Region, Italy].
AB  - INTRODUCTION: Medical records have an important role in the communication among
      different care providers and in forensic medicine. In Italy, information on
      completeness and correctness of medical records is scanty, whereas future
      hospital accreditation could take into account their quality as a proxy of good
      medical practice. PURPOSE: We performed a retrospective study in order to assess
      the quality of medical records in the Lazio region. METHODS: From all 37009
      hospital discharges for five different diseases in 123 hospitals (acute
      myocardial infarction (AMI), coronary artery bypass surgery, pneumonia,
      cerebrovascular disorders, breast surgery), registered in the Regional Hospital
      Information System, we selected a random sample of 2022 (5.5% of the total). Ten
      physicians, previously trained, reviewed the relative medical charts and filled
      in "ad hoc" questionnaires. RESULTS: A total of 1960 (97% of the target) charts
      were reviewed. Organization and structure of data recording strongly varied.
      Important differences were found across the diseases for various items: presence
      of anamnesis 98.1% (range: from 95.6% for breast surgery to 100% for AMI);
      presence of physical examination 92.7% (range: from 88.1% for breast surgery to
      98.5% for AMI), completeness of the daily medical records was good in 70.8%
      (range: from 34.2% for pneumonia to 93.9% for cerebrovascular disorders).
      Variability among different type of hospitals was also observed, being teaching
      hospitals and some private hospitals more accurate. CONCLUSIONS: Quality of
      medical records tended to vary across different type of hospitals and different
      diseases. Actions for improving the quality should be undertaken as a priority.
      Efforts have to be done in restructuring charts, creating guidelines and training
      caregivers. The development and application of computer based health information
      systems should help solving these problems.

PMID- 14969297
TI  - [Health care provider payment systems].
AB  - Health care provider payment systems regulate the relationship between patients,
      providers, and third payers in order to maximise benefits and minimise costs of
      the whole health care system. Health care providers could be paid by a price or a
      fee for service, by capitation systems, or by reimbursement of production costs.
      It would be interesting to develop innovative payment systems aimed to the
      payment of the entire health care pattern of patients. This would be particularly
      desirable for certain health conditions where it is impossible to divide the
      health care delivery pattern into single health services e.g. psychiatric care,
      long term and rehabilitation care.

PMID- 14969298
TI  - [Considerations about health risk management].
AB  - From the birth of doctrines of Risk Management to today a lot of time is passed.
      From the initial application in the field of the insurances and the management of
      the enterprises, theories inspired to the identification, evaluation and
      correction of connected risks to the activity and the industrial trial has been
      figurative to the health, field in which the application of these principles
      results to be how much never profit and productive of benefits above all for the
      patients that suffer consequences of errors but also for the physicians and the
      personnel that, perfectly inserted in an organization aware of the trials to put
      into effect, can bring their contribution to underline the weak points of the
      relief trial. The economic cost and consequences of errors can decrease if a new
      culture is established inspired to the learning and the communication of the
      adverse events, to minimize the possibility that they again occurs.

PMID- 14969299
TI  - [The medical specialty in Community Medicine].
AB  - The A. describes synthetically the evolution of the job profiles of the GP in
      Italy as a consequence of the introduction of the NHS in 1978 and of the
      development of a new Primary Health Care (PHC) in the Health Districts of the
      Local Health Units. According to the national and regional Health Regulations the
      GP should adopt the holistic approach in the treatment of the patients with the
      involvement of the community for the PHC and with the integration of the formal
      and informal, private and public, social services. The efforts to change the
      traditional profile of the GP both for the global, holistic, approach to the
      patients and for the community approach to the health needs and for the health
      promotion of the individuals and of the community raised several continuing and
      basic educational problems. They showed the opportunity to introduce in Italy the
      accademic discipline Community Medicine and the post-graduated School of
      Community Medicine as a clinical specialization. The role and the functions of
      the specialist in Community Medicine are specifically connected with the
      development of the PHC.

PMID- 14969300
TI  - [Health-related behaviour and HCV prevalence among elderly and younger adults in
      an isolated community close to Rome (Italy)].
AB  - The aim of this study has been to investigate the differences in the health
      related behaviour by means of a questionnaire in a sample of elderly (>54 years,
      1st generation) and younger adults (<54 years, 2nd generation, all of them
      sons/daughters of HCV positive subjects), given the high difference in HCV
      positive prevalence among the two groups (19.4% vs. 2.1%). Most (53.4% vs. 0.0%)
      of the 1st generation subjects used glass syringes while all the 2nd generation
      subjects used disposable syringes. Among the elderly, the frequency of
      hospitalisation (70% vs. 50%), transfusions (11.8% vs. 2.9%) and dental therapy
      by false dentists (52% vs. 0%) were higher. These results show that the use of
      non recyclable syringes is the main responsible for the drastic reduction of HCV
      circulation in the present community, and the consequent decrease in the risk for
      infection in younger subjects. Moreover, dental therapy was not related to an
      increased risk for infection, providing that the treatment has been made by a
      "true" dentist. Finally, the intrafamiliar transmission was not supported by the
      present data.

PMID- 14969301
TI  - [Typhoid fever and environmental contamination in Apulia Region, Italy].
AB  - The decrease of typhoid fever in Italy is described. In our country, the
      morbidity rate is now very close to 1/100,000, reached since the sixtie's in many
      european countries. It is highlighted the role of regions as Apulia and Campania
      which are contributing for more than 50% to the national morbidity. More
      specifically is analysed the endemic situation in the 12 AUSL of Apulia region
      allowing to evidentiate that the highest morbidity rates are found in the areas
      along the sea. Finally, based on the data collected from the investigations after
      the cholera outbreak in 1994, it is proved that the faecal contamination is
      responsible for the morbidity rate in Apulia 6.6/100,000 in 1999.

PMID- 14969302
TI  - [Environmental diffusion of Legionella spp and legionellosis frequency among
      patients with pneumonia: preliminary results of a multicentric Italian survey].
AB  - A multicentric Italian investigation on legionnaires' disease is in course to
      clarify host factors as well as pathogen associated characteristics involved in
      the infection/disease. The main goal of the research plan is to account for some
      critical aspects concerning identification and prevention of legionellosis. To
      improve knowledge on factors associated with Legionella spp colonisation in hot
      waters, to detect cases and to characterize risk factors in subjects which
      develop pneumonia are specific objectives of the research programme. Preliminary
      results show that hot waters of houses and hotels are frequently contaminated
      (22.6% and 54.6%, respectively), mainly by L. pneumophila. Microbial
      concentrations were low in domestic waters (<1.000 ufc/l), but higher in samples
      from the hotels (geom. mean 1.85 x 10(3) ufc/l). Warming system, age of the
      plant, type of building were risk factors significantly associated with
      Legionella spp positivity. The active surveillance on patients affected by
      pneumonia with search for Legionella urinary antigen allowed the identification
      of 34 cases, 3 of which of nosocomial origin, corresponding to 4.2% of the
      screened pneumonia. After informed consent, 26 subjects were recruited for a case
      control-study to clarify risk factors for the disease.

PMID- 14969303
TI  - [Cost analysis of toxoplasma infection control in pregnancy].
AB  - In Italy, the management of Toxoplasma infection screening in pregnant women is
      often unproductive and inefficient and generates a wide variability of costs.
      This study evaluated performance parameters in the screening management of a
      population of pregnant women, estimated its costs and compared them with the
      costs of a full application of Ministerial Documents of 1995 and 1998. We
      controlled until delivery 830 pregnant women who had done the first blood test
      between September 1st and December 31st 1997. The costs of direct and indirect
      testing were analysed using the Excel database and statistical software package.
      Of the 573 pregnant women defined 'susceptible' at the first test, only 240 (42%)
      did further blood tests during the II and III trimesters, 30% did no more tests
      and the remaining women adopted a heterogeneous behaviour. The mean cost of each
      screening was found to be euro 54.47/pregnancy and euro 60.05/pregnancy with a
      full application of the Ministerial Document of 1995. A full application of
      Ministerial Document of 1998, instead, would have involved a cost of euro
      94.28/pregnancy for 5 tests, euro 111.40/pregnancy for 6 tests and euro 128.51
      for 7 tests. The study shows that the management of toxoplasmosis screening
      during pregnancy needs greater attention to the prescription of tests, so that
      useless testing can be reduced and the efficacy of the screening improved, two
      important goals the Ministerial Documents were designed to achieve.

PMID- 14969304
TI  - [Prevalence of glycopeptide resistant enterococci in hospitalized patients and in
      the community in Calabria (Italy)].
AB  - The study evaluated prevalence of glycopeptide (vancomycin and teicoplanin)
      resistant enterococci (VRE) in hospitalized patients and in the community in
      Calabria (Italy). Rectal swabs were collected from hospitalized and community
      subjects. Information was gathered on demographics, ward and duration of hospital
      stay and antibiotics administered; in community subjects information on previous
      hospitalizations and antibiotics use in the previous year were also collected.
      Rectal swabs were plated on Enterococcosel agar alone and with addition of
      vancomycin (6 mg/l) and incubated aerobically at 37 degrees for 24-48 hours.
      Typical colonies were tested for Gram stain and catalase production. Enterococci
      were identified to the species level by biochemical tests. Antimicrobial
      susceptibility test and E-test were performed by the disk diffusion method to
      evaluate vancomycin and teicoplanin susceptibility. t-test and chi square test
      were performed to evaluate difference in means and proportions, respectively.
      Samples were collected from 211 subjects; 132 (62.6%) from community and 79
      (37.4%) from hospitals. Enterococci were isolated from 145 subjects (68.7%),
      72.7% and 62% in community and in hospital, respectively. The most frequent
      isolates were E. faecium (30.4%), followed by E. faecalis and E. durans (25.5%),
      and, finally, by Leuconostoc (18.6%). Only one E. faecium strain was resistant to
      both vancomycin and teicoplanin, isolated from a non-hospitalized 45 years old
      woman (1.3%). The results did not show emergence of VRE in our area, although
      surveillance to confirm these findings is needed, considering the substantial
      spread of antibiotics in hospitals and in the community.

PMID- 14969305
TI  - [Epidemiology of unintentional drowning in children younger than 5 years in
      Italy].
AB  - The objective of the study was to describe the epidemiology of unintentional
      drowning in Italy in the period 1983-1997, in the age-group 0-4 years. We used
      mortality data from the Italian National Statistical Institute (ISTAT), and
      calculated the potential years of life lost (PYLL), for the single age-group and
      for all the children aged 0-4 years, following the CDC method (age limit 65
      years). Only in 1983 the rate of mortality due to accidental drowning in the age
      group 0-4 years was over 1.00 per 100,000 inhabitants (1.27). In the male sex the
      rate was over 1/100,000 in 1983 (1.93), 1984 (1.18) and 1989 (1.03). In the
      females the higher rate reached was 0.66/100,000 (1984). Considering both
      genders, the lower rate was reached in 1997 (0.33/100,000), and it was 0.42 for
      males (1992) and 0.07 for females (1988). Considering all ages, statistically
      significant differences in the mean death rates were found by sex (0.8/100,000
      for males and 0.31/100,000 for females; t = 4.504; p < 0.0001). Considering the
      single age-groups, statistically significant differences in the mean death rates
      were found by sex only for 2, 3 and 4 years (respectively, p = 0.005; p = 0.001 e
      p < 0.0001). Considering all children, we estimated a PYLL of 15,750 years (PYLL
      for males representing 72.2%). The mean death rate for unintentional drowning in
      the age-group 0-4 years in Italy is lower than the mean vaues in other countries,
      but there is a clear need to lower this kind of death, that accounted for almost
      16,000 PYLL in the period 1983-1997.

PMID- 14969306
TI  - [Child sexual abuse primary prevention: outcome evaluation of a health education
      project implemented in Milan's elementary schools].
AB  - The study we present is aimed at evaluating the efficacy of a child sexual abuse
      prevention program that involved children attending 4th and 5th grade in Milan's
      (Italy) elementary schools. The project involved 53 classes (10 of 4th, 43 of 5th
      grade) during school year 2000-2001. Children filled a questionnaire before the
      beginning of the project and two months after the end; the questionnaire
      evaluates children's perception of risk and their self-efficacy skills in
      adopting protective strategies when involved in at risk situations. Final
      analysis has involved 674 children, 51.8% girls, 48.2% boys; 19.6% of children
      attended 4th grade, 80.4% 5th grade. Percentage of children that recognize the
      potential danger in the suggested at-risk situation is higher in post-test then
      in pre-test (87.9% vs 73.2%) and the number of them that does not adopt any self
      defence strategy decreases (from 35.3% to 21.0%). The project increased the
      number of children that know body puberal changes (from 16.0% to 32.8%).
      According to these results it is evident that the program increased children's
      capacity to recognize and use self defence strategies in at risk situations.
      These results call for a potential extention and replication of this health
      education program.

PMID- 14969307
TI  - [Health promotion and education in secondary schools: knowledge on drugs abuse].
AB  - To prevent behaviours at risk for the use of substances that induce dependence,
      some meetings have been planned with children primary school, age in which it's
      still possible to prevent the contact with drugs and children are more receptive.
      Two questionnaires have been given to the students, a pre-test before the
      interview, to value their knowledge about drugs, and a re-test after the
      interview, to value if the knowledge objectives suggested had been reached. After
      meeting the students seemed to be more informed because there were statistically
      significative differences between the percentages of the correct answers of the
      pre-test and the re-test.

PMID- 14969308
TI  - [Tobacco smoking among nursing students: behaviour and knowledge of the
      correlated risks].
AB  - This study was designed to assess knowledge and consumption of tobacco, during
      the three years of the university course for nurses in Bologna. A questionnaire
      consisting of items about personal details, smoking habits, and one open question
      about knowledge of health risks linked to tobacco consumption 505 students. 43%
      of males and 33% of females were current smokers. The males were mostly medium
      and heavy smokers (>11 cigarettes/day) and the females light smokers (<10/day).
      As regards knowledge an increase in both number and accuracy of the answers given
      by the third year students was seen. Suggestions for educational programs are
      given considering that the population in question is part of an "example group"
      who are supposed to play a role in influencing the behavior of the general
      population.

PMID- 14969309
TI  - [From the introduction to the possibility of moving beyond immunization
      obligation: considerations on the need for a guided procedure].
AB  - In Italy until sec. XIX, the beginning of vaccination duty allows to obtain some
      weighty aims in Public Health, like small pox eradication, polio and diphtheria
      elimination, or like the great reduction of tetanus and hepatitis B incidence. At
      the some, however, the vaccination duty doesn't allow to develop a "vaccination
      conscience" to do to accept the vaccines like the most important instrument, for
      effectiveness and utility, in the infectious diseases prevention. So, if from a
      side it's necessary to leave the vaccination duty from the another side it's
      necessary to make e leaded way of health education in the people and it's
      necessary to make a share of resources and aims in the sanitary world.

PMID- 14969310
TI  - [Mandatory or voluntary vaccinations? Juridical and medico-legal aspects].
AB  - The Italian juridical and legislative aspects of vaccination based on a
      compulsory system are presented considering the medico-legal questions. The
      prospective of a voluntary system, as anticipated by many normatives and other
      official documents, is examined. The experience of some local health authorities
      on cases of in observance of the vaccinal obligation are detailed Finally
      professional risks for vaccinal operators are examined and the need of specific
      guidelines for parents' consent to compulsory vaccination during infancy is
      prospected.

PMID- 14969311
TI  - [Risks and benefits of influenza and pneumococcal immunization in HIV-1 infected
      individuals].
AB  - Influenza and Streptococcus pneumoniae diseases can cause severe complications in
      HIV-1 infected individuals leading to increases in hospital admission and even
      death. Both vaccinations are recommended for such individuals, but some studies
      reported that such immunizations may stimulate an increase of HIV-1 viral load
      and decrease of CD4+ cells count. A review of published studies, including our
      studies carried out in HIV-1 infected former drugs addicts, indicates that
      influenza and pneumococcal vaccinations are well tolerated in individuals with
      HIV-1, and do not induce deterioration of the course of HIV-1 infection, even
      though the immune response to vaccination is lower than that one observed in
      immunocompetent individuals. Therefore the lack of significant changes of
      virological and immunological parameters indicates that such immunizations can be
      safely administrated to HIV-1 infected individuals.

PMID- 14969312
TI  - [Lysteria monocytogenes in samples of swines sent to the human alimentary chain].
AB  - Animal food-stuffs are known to be potential vehicles of Listeria monocytogenes.
      The contamination can be caused from processing or enviromental sources and from
      infected animals. This hypothesis has been checked in the present work. The
      authors found that 13.2% of 189 swines were carriers of Listeria monocytogenes,
      the microrganism was isolated from salivary glands, mesenterial gangles and
      tonsils. The authors suggest some preventive intervention to reduce both the
      environmental circulation of Listeria monocytogenes and the human risk of
      infection.

PMID- 14969313
TI  - [The quality of a restaurant service at a geriatric rehabilitation facility].
AB  - The aim of our study was to measure the quality of a restaurant service of a
      geriatric rehabilitation and long-term setting as it is perceived from patients
      compared with an objective measure of the quality. We have also verified the
      weight of the restaurant service on the whole quality of the hospital. Our data
      showed some problems in the organisation of the service, a substantially negative
      judgment from patients, the necessity to integrate subjective judgments with
      objective evaluations. The data confirmed also the importance that patients give
      to taste and variability of food and to the way in which it is presented. The
      results we obtained suggested an audit of the organisation of the restaurant
      service. The outcome of the proposed changes will be followed up and bring,
      eventually, to further arrangements.

PMID- 14969314
TI  - [Adolescent Body Mass Index data: what differences result using different
      reference standard curves?].
AB  - Childhood and adolescent obesity prevalence rates have steadily increased both in
      industrialised and developing countries in the last years. Data from literature
      show that BMI is an acceptable indicator to assess overweight and obesity also in
      children and adolescents. Different reference standard curves for BMI exist: the
      percentiles of Rolland-Chachera, Luciano, the National Center for Health
      Statistics, Cole and Cacciari. Nevertheless, different cut off points are used by
      the authors to identify underweight, overweight and obesity. The aim of the
      present study was to investigate what differences can emerge when comparing
      adolescent BMI using different references standard curves. Five hundreds and
      thirty-five adolescent subjects, aged 15.4 +/- 0.7 years, were recruited in Aosta
      Valley (Northen Italy). BMI was calculated according to the following equation:
      BMI = weight/height2 (kg/m2). The data obtained were distributed according to BMI
      percentiles and than compared with references standard curves. The comparison
      shows different results especially when underweight, overweight and obesity are
      identified. In conclusion, it can be asserted that BMI is an useful indicator to
      assess adiposity (overweight and obesity) in adolescent, but one should be
      cautious when comparing results based on different references.

PMID- 14969315
TI  - [TV, overweight and nutritional surveillance. Ads content, food intake and
      physical activity].
AB  - The relationship between television viewing and obesity in children and adults
      was examined in a large number of cross-sectional epidemiological studies. Some
      randomised, controlled trials confirmed the evidence that television viewing is a
      cause of increased body fatness. It seems of utility in nutritional surveillance
      to esteem time spent by children and adults in television watching and to
      evaluate ads contents and food preferences suggested by them. This editorial
      shows a two-years long analysis of food commercials broadcasted by the main
      Italian TV networks; food ads targeted on children, housewives and sport fans
      were evaluated; the relationship between television viewing, commercials and food
      intake or global lifestyle was investigated in a Piedmont's population (from
      Northern Italy). School projects aimed to reduce television viewing represent a
      promising strategy for preventing childhood obesity.

PMID- 14969316
TI  - [The new management regulation for hospital wastes].
AB  - The paper characterizes the main goals of the new regulations on the management
      of the hospital wastes. The motivations for which the previous regulations have
      been repealed are shown. The new possibilities of management and disposal are
      explained. The instruments are described by means of which the new regulations,
      maintaining the maximum protection of the health and the environment, aimed at
      the rationalization and the control of the costs, and to the attainment of it
      objectives, in agreement with the European directives of prevention of the
      production of wastes and recovery of matter and energy, through the attainment
      and the upgrade of the differentiated collection.

PMID- 14969317
TI  - [Microbiological characterization of solid wastes and aerosol in a municipal
      solid waste landfill site].
AB  - Authors report data about microbiological characterization of solid wastes and
      aerosol in the municipal solid waste landfill site in Poiatica (RE). In solid
      waste samples high values of total coliform and fecal coliform were observed
      (10(5)-10(6) CFU/g): total bacterial counts at 22 degrees, at 36 degrees and at
      44 degrees ranged from 10(7) to 10(9) CFU/g. Aerosol samples collected during
      waste movement in the landfill site showed values of total and fecal bacterial
      ranging from 10(3)-10(4) CFU/m3. Staphylococci and fungi reported the same values
      while streptococci, total and fecal coliform and spore evidenced lower values.
      Municipal solid wastes and aerosol have to be considered as an infective
      substrate: it is necessary to adopt protective barriers in occupationally exposed
      subjects.

PMID- 14969318
TI  - [Chemical-physical and microbiological survey in groundwater of Salento].
AB  - In order to know better the groundwater quality of Salento, chemical-physical and
      microbiological investigations were carried out on waters collected from 31 wells
      chosen after a preliminary study about the hydrogeologic features of the region.
      The analysis, conducted once in a month within the span of a year, pointed out a
      widespread contamination of faecal origin, which limits the employment
      (drinkable, irriguous) of groundwater because of possible health implications.
      The results of the chemical-physical analyses show how the groundwater of Salento
      is "contaminated" by sea water getting into the continent and which in some
      areas, also owing to excessive drawings, deteriorates its quality and compromises
      its irriguous use.

PMID- 14969319
TI  - [Exposure to water disinfection by-products and adverse pregnancy outcomes:
      results of a case-control study carried out in Modena (Italy)].
AB  - Chlorination By Products (CBPs) in drinking water have been associated with an
      increased risk of adverse pregnancy outcomes, such as small term birth (STB) and
      preterm delivery. Up to date epidemiological evidence is weakened by a generally
      inaccurate exposure assessment, often at an ecological level: in this study the
      exposure is evaluated at the individual level. A case control study with incident
      cases was performed in Modena between October 1999-September 2000. 332 subjects
      were enrolled: 93 preterm births (26th-37th week of pregnancy), 73 STB (from 38th
      week, and weight less than the lowest 10th percentile) and 166 controls. Exposure
      was assessed both by applying a questionnaire on personal habits and by personal
      water sampling directly at subjects' home. THMs were analysed in all samples,
      chlorite and chlorate in water samples treated with chlorine dioxide. Subjects
      usually drinking tap water were few (5.2%): most of them were living in areas
      supplied by water treated with chlorine dioxide (87%). Levels of THMs were low
      (mean: 0.73 microgram/l), while chlorite and chlorate concentrations were
      relatively high (mean: 217.8 microgram/l for chlorites and 95.2 microgram/l for
      chlorates). Preterm birth did not show any significant association with CBPs,
      while STB appeared significantly associated, after adjusting for many potential
      confounders, with CBPs induced by chlorine dioxide treatment, especially with
      levels of chlorate higher than 200 microgram/l (OR: 4.7; 95%CI: 1.15-19.72). The
      association between STB and chlorate must be investigated further as the number
      of water utilities applying chlorine dioxide as disinfection treatment is
      increasing.

PMID- 14969320
TI  - [Presence of disinfection by-products (DBPs) and other halogenated compounds in
      drinking water samples collected in the areas of Modena and Parma].
AB  - The Authors report data about the presence of Disinfection By-Products (DBPs) and
      other halogenated compounds in drinking water samples collected in the areas of
      Modena and Parma (20 water supplies). Trihalomethanes, chlorite and chlorate
      (only in water samples treated with chlorine dioxide), and halogenated compounds
      were investigated. On the whole, trihalomethanes were evidenced in the 85% of the
      samples (n. 285) at low levels, while chlorite and chlorate were present in the
      67% and 63% of the treated samples with chlorine dioxide (257 samples). Chlorite
      mean and median values were 225.70 microg/l and 136.75 microg/l respectively,
      ranging from 20 to 2000 microg/l. Chlorate concentrations were lower than
      chlorite: the mean value was 102.93 mg/l, while median level was 50 microg/l
      (range: 20-1500 microg/l). The high concentrations of chlorite and the wide range
      of values within each municipality plant in Modena and Parma suggest to
      investigate further in order to evaluate the human exposure in drinking water
      thoroughly.

PMID- 14969321
TI  - [Preliminary surveys about the use of "Mytilus galloprovincialis" as an
      accumulation matrix of bacteria in coastal waters].
AB  - A biomonitoring study using "Mytilus galloprovincialis" mussels was carried out,
      to estimate their possible employment as "natural indicators" of coastal
      bacterial pollution. The research was conducted from September 2001 to May 2002,
      twice in a month, near two coastal zones of Salento. We analysed both natural and
      cultivated mussels. The latter were placed in cages, after checking their
      starting level of microbiological pollution. The bacteriological analyses
      conducted simultaneously on mussels and their ambient water, were directed to the
      search of: total and faecal coliforms, faecal streptococci, Escherichia coli,
      Salmonella spp., Staphylococcus aureus and yeasts. In this preliminary study the
      mussels proved to be "sensitive indicators of faecal pollution", since they had
      an accumulation of the faecal indicators even if the water was not contaminated.
      Nevertheless a lower frequency in finding yeasts in the mussels (53.8%) in
      comparison with water (74.3%), the irregular presence of Salmonella spp. in water
      (3.75%) and its absence in bivalves, show the need of further studies, also
      through "in vitro" tests, in order to verify absorption/elimination kinetics of
      microorganisms.

PMID- 14969322
TI  - An outbreak of hepatitis C virus in a haemodialysis unit: molecular evidence of
      patient-to-patient transmission.
AB  - Hepatitis C virus (HCV) infection remains a major problem in haemodialysis units
      despite the risk decrease provided by anti-HCV screening of blood. The exact mode
      of transmission of HCV in the dialysis units remains unclear. To identify the
      route of the virus and the mechanisms of transmission an investigation into the
      outbreak of HCV infection in a haemodialysis unit on a molecular level was held:
      12 newly infected patients and 14 already infected were investigated by
      sequencing the 5' untranslated region of the viral genome. The results showed
      that 3 strains infected new cases and these strains matched those sequenced in
      already infected patients. Transmission occurred between patients treated on the
      same shift and also between different rooms. Console and blood or blood product
      contamination was excluded. Our study gave molecular evidence of patient-to
      patient transmission of HCV in a haemodialysis unit. Our data underline the
      importance of the strict enforcement of standard precautions to prevent HCV
      transmission and failure of the isolation of anti-HCV positive patients as
      preventive measure.

PMID- 14969323
TI  - [Guidelines for a prevalence survey of nosocomial infections in the University
      Hospital "Madre Teresa" in Tirana, Albania].
AB  - The authors present guidelines for the first prevalence survey of nosocomial
      infections in the University Hospital "Madre Teresa" in Tirana (almost 1,600
      beds), the only tertiary health-care centre in Albania. The survey is a joint
      project involving Italy and Albania, to be coordinated by the Italian National
      Health Institute. The paper describes goals, methodology and organization of the
      prevalence survey. The improvement of local expertise in epidemiology and
      microbiology is one of the most important goals. Therefore, Albanian personnel
      training and improvement of the infection microbiological diagnosis are
      fundamental aspects of the project.

PMID- 14969324
TI  - [Environmental concentrations of nitrous oxide and isoflurane in the operating
      theatre].
AB  - An environmental survey was carried out in the operating theatres of an Emilian
      hospital (North Italy) to ascertain: if concentrations of nitrous oxide (N2O) and
      isoflurane were within prescribed limits; if anesthetic pollution decreases when
      it is periodically controlled; if the degree of pollution from isoflurane can be
      predicted from N2O measurements. Three controls of anesthetic pollution were
      carried out at six month intervals using a photoacoustic spectrometry analyser.
      Mean concentrations of N2O were lower than the limits prescribed for renovated
      (50 ppm) or not refurbished (100 ppm) operating theatres in 58% of the surgical
      sessions examined. Mean concentrations of isoflurane were lower than the values
      proposed for halogenated anesthetics, used together with N2O (0.5 ppm) or alone
      (2 ppm) in 39% of the cases. Anesthetic pollution decreased only after the second
      control. Mean concentrations of isoflurane and N2O were correlated with a very
      good degree of association (r = 0.77). The survey highlights that pollution needs
      to be controlled in operating room because anesthetic levels often exceed the
      prescribed limits. Awareness of the problem is important to improve environmental
      conditions. N2O measurement is indicative of pollution from isoflurane but
      halogenated anesthetic must also be determined for a thorough evaluation of
      anesthetic pollution.

PMID- 14969325
TI  - [Satisfaction and critical aspects of inpatients care among patients with
      psoriasis].
AB  - OBJECTIVES: To evaluate satisfaction with care for psoriatic inpatients. Identify
      areas in need of interventions and actions to improve the satisfaction with care.
      METHODS: We analyzed 133 patients with psoriasis and 335 patients affected by
      other dermatological diseases in their first access at the hospital. Six
      determinants of satisfaction with care were investigated with a self administered
      questionnaire. Moreover the overall satisfaction was documented. Descriptive
      analysis and a multiple logistic regression analysis correcting for confounding
      factors were performed. Focus groups were conducted with patients to further
      investigate about specific aspects of relationships between patients and
      personnel. RESULTS: Psoriatic inpatients were less satisfied than other
      dermatological inpatients regarding Coordination of care, Information and
      education, Emotional support. Emotional support was the determinant with the
      smallest percentage of satisfied patients. Focus groups confirmed what was
      identified with the questionnaire and suggested necessary interventions.
      CONCLUSIONS: It is necessary to improve the communication skills of health
      personnel. Information for patients need to be enhanced and the management of
      psoriatic patients has to be improved.

PMID- 14969326
TI  - [Multicentric survey on hygienic aspects in private dental practice].
AB  - The aim of this research was to evaluate the knowledge of cross-infection hazards
      in private dental practices, and their control procedures. The survey, carried
      out by questionnaire in 11 Italian cities, showed that dental personnel do not
      completely follow the main procedures for infection control. The interviewed
      subjects usually wear gloves (95.5%), masks (90.1%) and glasses (91.2%), less
      frequently caps (23.9%) and coats (54.9%). They use steam sterilizers (92.9%) and
      periodically check the effectiveness (80.6%). Regarding individuals protection,
      20.5% is not vaccinated against HBV and only 55.2% of those previously vaccinated
      has checked their immunity. Moreover, the majority of subjects underestimate the
      infection hazards especially for air-transmitted diseases.

PMID- 14969327
TI  - [Comparison between different methods to monitor the microbial level of indoor
      air contamination in the dental office].
AB  - There is no unanimous consensus on the best methodology to monitor the microbial
      contamination level of the air in the dental offices. Therefore, we compared a
      precise but expensive and complex active air sampler (Surface Air System--SAS)
      with a passive method (Air Microbiological Index--AMI) and a microbial parameter
      of salivary microrganisms, (oral streptococci--OS), with other, more simply
      detectable, yet more generic, parameters (staphilococci--ST total viable flora-
      TVF). We tested the various combinations of systems and parameters in three multi
      chair dental departments, for two different weekdays, before (T0) and during (T1)
      the working period. Using non-parametric statistical tests we analysed, (i) the
      difference between T0 and T1 contamination levels assessed by various methods, in
      order to confirm their efficacy; (ii) the association between parameters, in
      order to assess whether generic parameters were as reliable as the specific
      parameter; (iii) the association between sampling systems, in order to test
      whether AMI could efficaciously substitute the active samplers. The microbial
      levels were significantly higher at T1 than at T0, excluding ST assessed by SAS.
      The parameters were highly inter-correlated. However, for low SO levels, the
      level of the association of this parameter with the others decreased. The results
      provided by SAS and AMI were also significantly correlated. However, for low
      contamination levels this association was not significant. In conclusion, the
      complex and expensive method (SO level assessed by SAS) seems more reliable for
      low aerial contamination levels, whereas for high levels, more simple and cheap
      methods could also be used.

PMID- 14969328
TI  - [Epidemiology of work related injuries in young people: results of a survey
      carried out in Modena (Italy) between January and June 2000].
AB  - Work related injuries, above all those involving young people, are an important
      health and social issue, even though up to now small attention has been deserved
      in spite of the presence of about 68 workers per 1000 young people and the
      occurrence of 27400 injures in young people in 2000 in Italy. This study was
      aimed at improving the knowledge on work related injures occurring in Modena in
      14-17 year old subjects in the period January-June 2000. A descriptive
      epidemiological study was carried out. Information was collected at the two
      emergency departments operating in Modena by checking hospital and INAIL records.
      Injures were defined as events caused by a violent external cause producing one
      or more lesions. Injuries were defined as work related when occurring during
      working activities or "in itinere". Work related injures and other injures were
      compared using the different statistical methods. Work related injuries occurring
      in young people during January-June 2000 in Modena were 76 (6-month incidence:
      1.5 per 100 subjects of the same age) and represent 8.5% of all injuries. The
      most involved subjects were 17 year old males working in the industrial field,
      and in most cases prognoses were lasting less than 8 days. A Cluster Analysis
      identified two types of injures: the "in itinere" ones which resulted similar to
      the road accidents, both for body sites involved and for the way of occurrence
      and the injuries occurring at the working place characterised by a high frequency
      of lesions concerning hand, head, above all eyes. The study showed a remarkable
      incidence of work related injuries among 14-17 year old subjects in Modena in the
      first 6 months of 2000. Nevertheless many difficulties in finding information
      raised during the survey: a higher accuracy and completeness in collecting and
      recording of the data is needed to better define the epidemiological aspects of
      this issue.

PMID- 14969329
TI  - [On a new species of sand flea from Ecuador and tungiasis, a problem of Public
      Health in many developing countries].
AB  - The authors recently described a new species of sand flea (genus Tunga) occurred
      in goat, sheep, cow, pig and man, in the Andean village of S.ta Isabel (Ecuador)
      and named Tunga trimamillata. Its most important morphological characteristics
      are: slightly larger dimensions than T. penetrans, both in male and female;
      presence on the anterior extremity of gravid female of three rounded humps
      surrounding head and thorax; length of the first segment of maxillary palpi which
      is longer than each of the other three. The importance of this parasite is due to
      the fact that it can cause the same damages as T. penetrans both in humans and
      domestic animals, with conseguent walking difficulties and local or generalized
      infections. For breeders, economic losses can be remarkable. Tungiasis is a
      serious problem of Public Health in many countries of Latin America and
      Subsaharian Africa, and it can be considered in these localities as an indicator
      of underdevelopment and poor hygiene conditions.

PMID- 14969330
TI  - Control of encapsulation efficiency and initial burst in polymeric microparticle
      systems.
AB  - Initial burst is one of the major challenges in protein-encapsulated
      microparticle systems. Since protein release during the initial stage depends
      mostly on the diffusional escape of the protein, major approaches to prevent the
      initial burst have focused on efficient encapsulation of the protein within the
      microparticles. For this reason, control of encapsulation efficiency and the
      extent of initial burst are based on common formulation parameters. The present
      article provides a literature review of the formulation parameters that are known
      to influence the two properties in the emulsion-solvent evaporation/extraction
      method. Physical and chemical properties of encapsulating polymers, solvent
      systems, polymer-drug interactions, and properties of the continuous phase are
      some of the influential variables. Most parameters affect encapsulation
      efficiency and initial burst by modifying solidification rate of the dispersed
      phase. In order to prevent many unfavorable events such as pore formation, drug
      loss, and drug migration that occur while the dispersed phase is in the semi
      solid state, it is important to understand and optimize these variables.

PMID- 14969331
TI  - Some pyridazinone and phthalazinone derivatives and their vasodilator activities.
AB  - In this study, 6-[(4-arylidene-2-phenyl-5-oxoimidazolin-1-yl)phenyl]-4,5-dihydro
      3(2H)-pyridazinone and 4-[(4-arylidene-2-phenyl-5-oxoimidazolin-1-yl)phenyl]
      1(2H)-phthalazinone derivatives were synthesized by reacting 6-(4-aminophenyl)
      4,5-dihydro-3(2H)-pyridazinone or 4-(4-aminophenyl)-1(2H)-phthalazinone compound
      with different 4-arylidene-2-phenyl-5(4H)-oxazolone derivatives. The vasodilator
      activities of the compounds were examined both in vitro and in vivo. Some
      pyridazinone derivatives showed appreciable activity.

PMID- 14969332
TI  - Synthesis of 2-(4-hydroxyphenyl)benzofurans and their application to beta-amyloid
      aggregation inhibitor.
AB  - The facile synthesis of a series of 2-(4-hydroxyphenyl)benzofurans (4a-e) is
      described. The one-pot reaction of 4-substituted phenols with the chloride 1 in
      the presence of zinc chloride afforded 3-methylthio-2-(4
      acetoxyphenyl)benzofurans (2a-e). The compounds 4a-e were obtained from the
      hydrolysis of 2a-e followed by the desulfurization of the resulting 3-methylthio
      2-(4-hydroxyphenyl)benzofurans (3a-e). 5-Methyl-3-p-toluoyl-2-[4-(3
      diethylaminopropoxy)phenyl]benzofuran (7), a beta-amyloid aggregation inhibitor,
      was synthesized by three steps starting from 4a.

PMID- 14969333
TI  - Identification of homoserine lactone derivatives using the methionine
      functionalized solid phase synthesis by gas chromatography/mass spectrometry.
AB  - Combinatorial homoserine lactone mixtures and individual products were obtained
      from the methionine-functionalized resin in solid-phase synthesis. The four-step
      process consisting of a coupling step of an N-Fmoc-L-methionine, deprotection of
      N-Fmoc group, N-coupling with a carboxylic acid, and cleavage reaction through a
      polymer supported strategy is described. Gas chromatography-mass selective
      detector (GC-MSD) techniques provide the most powerful methods for identifying
      both the combinatorial mixtures and individual products.

PMID- 14969334
TI  - Electrochemical behavior and square wave voltammetric determination of
      doxorubicin hydrochloride.
AB  - The electrochemical behavior of doxorubicin hydrochloride was investigated by
      cyclic voltammetry (CV) and square wave voltammetry (SWV). From CV and SWV
      studies of doxorubicin hydrochloride in the acetate buffers of various pH values,
      it was found that protons were involved in the reduction of the antibiotic at the
      H+/e- ratio at one (deltaEp/pH = -53 approximately -61 mV at 23 degrees C),
      proposing the electrochemical reduction of the quinone moiety in its
      anthraquinone aglycone. Its electrochemical behavior was pseudo-reversible in the
      acetate buffer of pH 3.5 by exhibiting the well-defined single cathodic and
      anodic waves and the ratio of Ip(a)/Ip(c) at approximately one over the scan
      rates of 10 approximately 100 mV/s. Fast and sensitive SWV showing a single peak
      of doxorubicin has been applied for its quantitative analysis using an acetate
      buffer of pH 3.5. A linearity was obtained when the peak currents (Ip) were
      plotted against concentrations of doxorubicin in the range of 5.0 x 10(-7) M
      approximately 1.0 x 10(-5) M with a detection limit of 1.0 x 10(-7) M.

PMID- 14969335
TI  - Distribution of (-)-yatein in Cupressaceae family analysed by high performance
      liquid chromatography.
AB  - The method for the chiral analysis of (-)-yatein was developed and the
      distribution of this component in the plants of three genera like Juniperus,
      Thuja and Chamaecyparis belonging to Cupressaceae family was examined. The chiral
      analysis of (-)-yatein from the plants was carried out by high performance liquid
      chromatography on (R,R)-Whelk-O1 column using 81 v/v% methanol as mobile phase.
      The yatein content in the leaves of Juniperus was the highest in compare with
      that of the other two genera, providing the possibility of the chemical
      discrimination of the plants in Juniperus from the other plants in the
      Cupressaceae family. In general, the yatein content in the leaves was much higher
      than that in the twigs. This method could be applied for the quality control of (
      )-yatein in the plants belonging to Cupressaceae family.

PMID- 14969336
TI  - Phytochemical constituents from Diodia teres.
AB  - All ten compounds were isolated from the methanolic extract of the whole plants
      of Diodia teres through repeated silica gel and Sephadex LH-20 column
      chromatography. Their chemical structures were elucidated as three iridoid
      glycosides, asperuloside, geniposidic acid and asperulosidic acid, a coumarin
      glycoside, scopolin, and six flavonoids, rutin, kaempferol-3-O-rutinoside,
      quercitrin, astragalin, isoquercitrin and quercetin by spectroscopic analysis.

PMID- 14969337
TI  - Isolation of flavonol rhamnosides from Loranthus tanakae and cytotoxic effect of
      them on human tumor cell lines.
AB  - Loranthus tanakae Fr. et Sav. (Loranthaceae) is a species of mistletoe, a
      semiparasitic plant growing on the branches of Quercus and Betula species as host
      trees. In our ongoing search for bioactive compounds from endemic species in
      Korea, we have investigated to isolate the chemical constituents responsible for
      the antitumor effect of the MeOH extract of L. tanakae. The ethylacetate soluble
      part of the MeOH extract demonstrated a marginal inhibition on the proliferation
      of the tumor cell lines such as A549 (non small cell lung), SK-OV-3 (ovary), SK
      MEL-2 (melanoma), XF498 (central nerve system), and HCT-15 (colon) in vitro.
      Thus, the activity-guided isolation procedure upon the ethylacetate soluble part
      of the extract has been carried out and finally four flavonoid rhamnopyranosides
      (1-4) were isolated as active principle. The structures of 1-4 were elucidated by
      the physicochemical and spectral data as rhamnetin 3-O-alpha-L-rhamnoside (1),
      quercetin 3-O-alpha-L-rhamnoside (2), rhamnocitrin 3-O-alpha-L-rhamnoside (3),
      and kaempferol 3-O-alpha-L-rhamnoside (4).

PMID- 14969338
TI  - Anti-diabetic effects of DA-11004, a synthetic IDPc inhibitor in high fat high
      sucrose diet-fed C57BL/6J mice.
AB  - DA-11004 is a synthetic, potent NADP-dependent isocitrate dehydrogenase (IDPc)
      inhibitor where IC50 for IDPc is 1.49 microM. The purpose of this study was to
      evaluate the effects of DA-11004 on the high fat high sucrose (HF)-induced
      obesity in male C57BL/6J mice. After completing a 8-week period of
      experimentation, the mice were sacrificed 1 hr after the last DA-11004 treatment
      and their blood, liver, and adipose tissues (epididymal and retroperitoneal fat)
      were collected. There was a significant difference in the pattern of increasing
      body weight between the HF control and the DA-11004 group. In the DA-11004 (100
      mg/kg) treated group the increase in body weight significantly declined and a
      content of epididymal fat and retroperitoneal fat was also significantly
      decreased as opposed to the HF control. DA-11004 (100 mg/ kg) inhibited the IDPc
      activity, and thus, NADPH levels in plasma and the levels of free fatty acid
      (FFA) or glucose in plasma were less than the levels of the HF control group. In
      conclusion, DA-11004 inhibited the fatty acid synthesis in adipose tissues via
      IDPc inhibition, and it decreased the plasma glucose levels and FFA in HF diet
      induced obesity of C57BL/6J mice.

PMID- 14969339
TI  - Acetylcholinesterase inhibitors from the twigs of Vaccinium oldhami Miquel.
AB  - In the course of finding Korean natural products with acetylcholinesterase (AChE)
      inhibitory activity, we found that a methanolic extract of the twigs of Vaccinium
      oldhami significantly inhibited AChE. Bioassay-guided fractionation of the
      methanolic extract resulted in the isolation of two compounds, taraxerol (1) and
      scopoletin (2), as active constituents. These compounds inhibited AChE activity
      in a dose-dependent manner, and the IC50 values of compounds 1 and 2 were 33.6
      (79 microM) and 10.0 (52 microM) microg/mL, respectively.

PMID- 14969340
TI  - Anti-allergic activity of 18beta-glycyrrhetinic acid-3-O-beta-D-glucuronide.
AB  - Glycyrrhizin (18beta-glycyrrhetinic acid-3-O-beta-D-glucuronopyranosyl-(1 --> 2)
      beta-D-glucuronide, GL) was transformed to 18beta-glycyrrhetinic acid-3-O-beta-D
      glucuronide (GAMG) by Streptococcus LJ-22. The antiallergic activities of GL and
      GAMG was measured using a RBL cell assay system and contact hypersensitivity
      model mice. GAMG exhibited anti-allergic activity with IC50 values of 0.28 mM.
      GAMG, which is sweeter than GL, and 18beta-glycyrrhetinic acid, which is a GAMG
      metabolite by human intestinal bacteria, also inhibited the passive cutaneous
      anaphylaxis and skin contact inflammation. In conclusion, GAMG may be useful as a
      new sweet food additive and an anti-allergic agent.

PMID- 14969341
TI  - Transformation of ginseng saponins to ginsenoside Rh2 by acids and human
      intestinal bacteria and biological activities of their transformants.
AB  - When ginseng water extract was incubated at 60 degrees C in acidic conditions,
      its protopanaxadiol ginsenosides were transformed to ginsenoside Rg3 and delta20
      ginsenoside Rg3. However, protopanaxadiol glycoside ginsenosides Rb1, Rb2 and Rc
      isolated from ginseng were mostly not transformed to ginsenoside Rg3 by the
      incubation in neutral condition. The transformation of these ginsenosides to
      ginsenoside Rg3 and delta20-ginsenoside Rg3 was increased by increasing
      incubation temperature and time in acidic condition: the optimal incubation time
      and temperature for this transformation was 5 h and 60 degrees C resepectively.
      The transformed ginsenoside Rg3 and delta20-ginsenoside Rg3 were metabolized to
      ginsenoside Rh2 and delta20-ginsenoside Rh2, respectively, by human fecal
      microflora. Among the bacteria isolated from human fecal microflora, Bacteroides
      sp., Bifidobacterium sp. and Fusobacterium sp. potently transformed ginsenoside
      Rg3 to ginsenoside Rh2. Acid-treated ginseng (AG) extract, fermented AG extract,
      ginsenoside Rh2 and protopanaxadiol showed potent cytotoxicity against tumor cell
      lines. AG extract, fermented AG extract and protopanaxadiol potently inhibited
      the growth of Helicobacter pylori.

PMID- 14969342
TI  - Mistletoe lectin induces apoptosis and telomerase inhibition in human A253 cancer
      cells through dephosphorylation of Akt.
AB  - Mistletoe lectin has been reported to induce apoptosis in different cancer cell
      lines in vitro and to show antitumor activity against a variety of tumors in
      animal models. We previously demonstrated the Korean mistletoe lectin (Viscum
      album var. coloratum, VCA)-induced apoptosis by down-regulation of Bcl-2 and
      telomerase activity and by up-regulation of Bax through p53- and p21-independent
      pathway in hepatoma cells. In the present study, we observed the induction of
      apoptotic cell death through activation of caspase-3 and the inhibition of
      telomerase activity through transcriptional down-regulation of hTERT in the VCA
      treated A253 cells. We also observed the inhibition of telomerase activity and
      induction of apoptosis resulted from dephosphorylation of Akt in the survival
      signaling pathways. In addition, combining VCA with the inhibitors of
      phosphatidylinositol 3-kinase (PI3-kinase) upstream of Akt, wortmannin and
      LY294002 showed an additive inhibitory effect of telomerase activity. In
      contrast, the inhibitor of protein phosphatase 2A (PP2A), okadaic acid inhibited
      VCA-induced dephosphorylation of Akt and inhibition of telomerase activity. Taken
      together, VCA induces apoptotic cell death through Akt signaling pathway in
      correlated with the inhibition of telomerase activity and the activation of
      caspase-3. From these results, together with our previous studies, we suggest
      that VCA triggers molecular changes that resulting in the inhibition of cell
      growth and the induction of apoptotic cell death of cancer cells, which suggest
      that VCA may be useful as chemotherapeutic agent for cancer cells.

PMID- 14969343
TI  - DA-125, a new antitumor agent, inhibits topoisomerase II as topoisomerase poison
      and DNA intercalator simultaneously.
AB  - DA-125, a novel derivative of adriamycin, is known for its anti-cancer activity.
      In this study, the inhibitory mechanism of DA-125 on topoisomerase was
      investigated in the simian virus 40 (SV40) replicating CV-1 cell by studying the
      SV40 DNA replication intermediates and DNA-topoisomerase complexes. DNA-protein
      complexes that were formed in the drug-treated cells were quantitated by using a
      glass filter assay. SV40 DNA replication intermediates that were accumulated in
      the drug-treated CV-1 cell were analyzed in a high resolution gel. DA-125 did not
      accumulate B-dimers of SV40 DNA replication intermediates which were found in the
      adriamycin-treated CV-1 cells. DA-125 induced a dose-dependent formation of the
      DNA-protein complexes, while adriamycin did not. When adriamycin and etoposide
      (VP16) were added to the SV40-infected cells at the same time, adriamycin blocked
      the formation of the DNA-protein complexes induced by VP16 in a dose-dependent
      manner. However, DA-125 blocked the formation of the DNA-protein complexes
      induced by VP16 up to the maximum level of the DNA-protein complexes that were
      induced by DA-125 alone. Adriamycin and DA-125 did not inhibit the formation of
      the DNA-protein complexes that were caused by camptothecin, a known topoisomerase
      I poison. DA-125 is bifunctional in inhibiting topoisomerase II because it
      simultaneously has the properties of the topoisomerase II poison and the DNA
      intercalator. As a topoisomerase II poison, DA-125 alone induced dose-dependent
      formation of the DNA-protein complexes. However, as a DNA intercalator, it
      quantitatively inhibited the formation of the DNA-protein complexes induced by a
      strong topoisomerase II poison VP16. Furthermore considering that the levels of
      the DNA-protein complex induced by VP16 were decreased by DA-125 in terms of the
      topoisomerase II poison, we suggest that DA-125 has a higher affinity to the drug
      binding sites of DNA than VP16 has.

PMID- 14969344
TI  - The inhibitory principle of lipopolysaccharide-induced nitric oxide production
      from Inula britannica var. chinensis.
AB  - A sesquiterpene lactone, 1-O-acetyl-4R,6S-britannilactone (1) isolated from the
      flowers of Inula britannica L. var. chinensis (Rupr.) Reg. (Compositae), was
      found as an iNOS inhibitory constituent for the first time with an IC50 value of
      22.1 microM which is more potent than the positive control, L-N6-(1
      iminoethyl)lysine (IC50 = 33.7 microM). Structure of compound 1 was identified by
      1D and 2D NMR experiments and by comparison with the reference standard.

PMID- 14969345
TI  - Involvement of nitric oxide during in vitro fertilization and early embryonic
      development in mice.
AB  - Nitric oxide (NO) has emerged as an important intracellular and intercellular
      messenger, controlling many physiological processes and participating in the
      fertilization process via the autocrine and paracrine mechanisms. This study
      investigated whether nitric oxide synthase (NOS) inhibitior (L-NAME) and L
      arginine could regulate in vitro fertilization and early embryonic development in
      mice. Mouse epididymal spermatozoa, oocytes, and embryos were incubated in
      mediums of variable conditions with and without L-NAME or L-arginine (0.5, 1, 5
      and 10 mM). Fertilization rate and early embryonic development were significantly
      inhibited by treating sperms or oocytes with L-NAME (93. 8% vs 66.3%, 92.1% vs
      60.3%), but not with L-arginine. In contrast, fertilization rate and early
      embryonic development were conspicuously reduced when L-NAME or L-arginine was
      added to the culture media for embryos. Early embryonic development was inhibited
      by microinjection of L-NAME into the fertilized embryos in a dose-dependent
      manner, but only by high concentrations of L-arginine. These results suggest that
      a moderate amount of NO production is essential for fertilization and early
      embryo development in mice.

PMID- 14969346
TI  - Effects of dopaminergic drugs on the mast cell degranulation and nitric oxide
      generation in RAW 264.7 cells.
AB  - Effects of dopaminergic drugs on the degranulation of mast cells (RBL-2H3 cells)
      and the nitric oxide production from macrophage cells (RAW 264.7) were studied.
      Among the dopaminergic agonists and antagonists tested, bromocriptine, 7-OH-DPAT,
      haloperidol, and clozapine showed potent inhibitions of mast cell degranualtion
      (IC50 value, 5 microM). However, these dopaminergic agents did not affect the
      tyrosine phosphorylations of the signaling components of the high affinity IgE
      receptor (FcepsilonRI), such as Syk, PLCgamma1, and PLCgamma2.; This suggested
      that these signaling components were not involved in the inhibition of the mast
      cell degranulation by these compounds. On the other hand, dopamine,
      bromocriptine, 7-OH-DAPT, and haloperidol markedly inhibited the nitric oxide
      production from RAW 264.7 cells (IC50 values, 10-20 microM). Bromocriptine, a
      dopamine agonist that is routinely used for the treatment of Parkinsons disease,
      inhibited the expression of the inducible nitric oxide synthase at an early stage
      of the LPS-induced protein expression in a dose-dependent manner. The results
      suggested that these dopaminergic agents, when used for the treatment of dopamine
      receptors-related diseases, such as Schizophrenia or Parkinsons disease, might
      have additional beneficial effects.

PMID- 14969347
TI  - Isoflavones extracted from Sophorae fructus upregulate IGF-I and TGF-beta and
      inhibit osteoclastogenesis in rat bone marrow cells.
AB  - Isoflavones have been a central subject in research on the natural phytoestrogens
      found in Leguminosae. Their effects on bone formation and remodeling are
      important in that they can act like estrogen by binding on estrogen receptors on
      the target cell surface. We, therefore, believed that isoflavones may help in the
      treatment of patients with estrogen deficiency disease such as estrogen
      replacement therapy (ERT) for osteoporosis. As commonly known, osteoporosis is
      one of the hormonal deficiency diseases, especially in menopausal women. When
      estrogen is no longer produced in the body a remarkable bone remodeling process
      occurs, and the associated events are regulated by growth factors in the
      osteoblast lineage. In the present study, we investigated whether isoflavones
      (Isocal) extracted from Sophorae fructus affect the growth factors IGF-I and TGF
      beta that have been known to be related with bone formation. In the study, we
      found that the active control (PIII) effectively enhanced the level of nitric
      oxide (NO) and growth factors, and thereby inhibited osteoclastogenesis. The most
      efficient concentration was 10(-8)% within five days, whereas the comparative
      control (soybean isoflavone) was not as effective even at a lower concentration.
      In conclusion, the products which contain enriched glucosidic isoflavone and
      nutrient supplements such as shark cartilage and calcium can be used for
      osteoporosis therapy by enhancing the production of IGF-I and TGF-beta.
      Furthermore, the NO produced through endothelial constitutive NO synthase (ecNOS)
      may play a role in inhibiting bone reabsorption.

PMID- 14969348
TI  - Anti-oxidant activities of Acanthopanax senticosus stems and their lignan
      components.
AB  - The antioxidant activities of Acanthopanax senticosus stems were evaluated in
      CCl4-intoxicated rats. The n-butanol fraction from the water extract of the
      stems, when pretreated orally at 200 mg/kg/day for 7 consecutive days in rats,
      was demonstrated to exhibit significant increases in antioxidant enzyme
      activities such as hepatic cytosolic superoxide dismutase, catalase and
      glutathione peroxidase by 30.31, 19.82 and 155%, respectively. The n-butanol
      fraction whereas showed a significant inhibition of serum GPT activity (65.79%
      inhibition) elevated with hepatic damage induced by CCl4-intoxication.
      Eleutheroside B, a lignan component, isolated from the n-butanol fraction was
      found to cause a moderate free radical scavenging effect on DPPH, its scavenging
      potency as indicated in IC50 value, being 58.5 microM. These results suggested
      that the stems of A. senticosus possess not only antioxidant but also
      hepatoprotective activities.

PMID- 14969349
TI  - Role of Kupffer cells in the vasoregulatory gene expression during hepatic
      ischemia/reperfusion.
AB  - Hepatic microcirculatory failure is a major component of reperfusion injury in
      the liver. Recent data provided some evidence that endothelium-derived
      vasoconstrictors and vasodilators may be functionally important to the control of
      the total hepatic blood flow under these conditions of circulatory failure. Since
      Kupffer cells provide signals that regulate the hepatic response in
      ischemia/reperfusion (I/R), the aim of this study was to investigate the role of
      Kupffer cells in the I/R-induced imbalance of vasoregulatory gene expression.
      Rats were subjected to 60 min hepatic ischemia, followed by 5 h of reperfusion.
      The Kupffer cells were inactivated by gadolinium chloride (GdCl3, 7.5 mg/kg body
      weight, intravenously) 1 day prior to ischemia. Liver samples were obtained 5 hrs
      after reperfusion for RT-PCR analysis of the mRNA for genes of interest:
      endothelin-1 (ET-1), its receptors ETA and ETB, endothelial nitric oxide synthase
      (eNOS), inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1). ET-1
      mRNA expression was increased by I/R. mRNA levels for ETA receptors showed no
      change, whereas ETB receptor transcripts increased in the I/R group. The
      increases in ET-1 and ETB mRNA were not prevented by the GdCl3 pretreatment. The
      mRNA levels for iNOS and eNOS significantly increased within the I/R group with
      no significant difference between the I/R group and the GdCl3-treated I/R group.
      HO-1 mRNA expression significantly increased in the I/R group and this increase
      was attenuated by GdCl3. In conclusion, we have demonstrated that an imbalance in
      hepatic vasoregulatory gene expression occurs during I/R. Our findings suggest
      that the activation of Kupffer cells is not required for I/R-induced hepatic
      microvascular dysfunction.

PMID- 14969350
TI  - Preparation of alginate/chitosan microcapsules and enteric coated granules of
      mistletoe lectin.
AB  - The aqueous extract of European mistletoe (Viscum album, L.) has been used in
      cancer therapy. The purified mistletoe lectins, main components of mistletoe,
      have demonstrated cytotoxic and immune-system-stimulating activities. Korean
      mistletoe (Viscum album L. coloratum), a subspecies of European mistletoe, has
      also been reported to possess anticancer and immunological activities. A
      galactose- and N-acetyl-D-galactosamine-specific lectin (Viscum album L.
      coloratum agglutinin, VCA) with Mr 60 kDa was isolated from Korean mistletoe.
      Mistletoe preparations have been given subcutaneously due to the low stability of
      lectin in the gastrointestinal (GI) tract. In the present study, we investigated
      the possibility of alginate/chitosan microcapsules as a tool for oral delivery of
      mistletoe lectin. In addition, our strategy has been to develop a system composed
      of stabilizing cores (granules), which contain mistletoe lectin, extract or
      powder, coated by a biodegradable polymer wall. Our results indicated that
      successful incorporation of VCA into alginate/chitosan microcapsules has been
      achieved and that the alginate/chitosan microcapsule protected the VCA from
      degradation at acidic pH values. And coating the VCA with polyacrylic polymers,
      Eudragit, produced outstanding results with ideal release profiles and only
      minimal losses of cytotoxicity after manufacturing step. The granules prepared
      with extract or whole plant produced the best results due to the stability in the
      extract or whole plant during manufacturing process.

PMID- 14969351
TI  - Kangaroos avoid eating seedlings with or near others with volatile essential
      oils.
AB  - Preliminary studies indicate that western grey kangaroos browse seedlings of non
      Myrtaceae species rather than Myrtaceae. Seven morphologically-matched species
      pairs of Myrtaceae/non-Myrtaceae placed at three field sites showed that
      kangaroos avoided the essential-oil-containing Myrtaceae, but readily consumed
      the matched essential-oil-lacking non-Myrtaceae. The one exception
      (Pittosporaceae) had limited herbivory and was later found to possess two
      essential oils in its leaves. Gas chromatography and mass-spectra showed the
      seven Myrtaceae plants contain between 2 and 9 essential oils in their leaves,
      particularly the highly volatile monoterpene, 2,5-dimethyl-3-methylene-1,5
      heptadine. Three of the above species pairs were used to gauge their
      effectiveness as nurse plants for a highly palatable legume. Plants placed beside
      Myrtaceae nurse plants were less browsed than those placed beside non-Myrtaceae
      nurse plants. We conclude that western grey kangaroos use olfactory cues to avoid
      foliage containing potentially toxic essential oils, and that this also has
      implications for seedling recruitment patterns in regenerating communities.

PMID- 14969352
TI  - Sour-taste tolerance in four species of nonhuman primates.
AB  - The taste of most fruits is characterized by a mixture of sensations termed sweet
      and sour by humans, and the food selection behavior of primates suggests that
      they may use the relative salience of sweetness and sourness to assess
      palatability of potential food items. Therefore, taste responses of six squirrel
      monkeys, five pigtail macaques, four olive baboons, and four spider monkeys to
      sweet-sour taste mixtures were assessed in two-bottle preference tests of brief
      duration (2 min). Monkeys were given the choice between a reference solution of
      50 mM sucrose and mixtures containing 10, 30, or 50 mM citric acid plus 10, 20,
      50, 100, 200, 400, 800, or 1000 mM sucrose. We found that the four species
      differed markedly in their acceptance of physiological concentrations of sour
      tasting citric acid. Whereas olive baboons showed the highest degree of sour
      taste tolerance and actually preferred most of the sweet-sour taste mixtures over
      sweet-tasting reference solutions, squirrel monkeys showed the lowest degree of
      sour-taste tolerance and rejected most of the sweet-sour taste mixtures even when
      they contained considerably more sucrose than the reference solutions. Additional
      tests demonstrated that the preference for sweet-sour taste mixtures was not
      based on masking effects. Rather, the animals perceived both the sweetness and
      the sourness of the taste mixtures and made a trade-off between the attractive
      and aversive properties of the two taste qualities. The results of this study
      suggest that the proximate reason for the marked differences in acceptance of
      sweet-sour taste mixtures are differences among species in the hedonic evaluation
      of the sour taste of citric acid. Possible ultimate reasons, which do not
      necessarily exclude, but may complement each other, include evolutionary
      adaptation to dietary specialization, avoidance of competition pressure, and
      phylogenetic relatedness.

PMID- 14969353
TI  - Induction of direct and indirect plant responses by jasmonic acid, low spider
      mite densities, or a combination of jasmonic acid treatment and spider mite
      infestation.
AB  - Jasmonic acid (JA) and the octadecanoid pathway are involved in both induced
      direct and induced indirect plant responses. In this study, the herbivorous mite,
      Tetranychus urticae, and its predator, Phytoseiulus persimilis, were given a
      choice between Lima bean plants induced by JA or spider mites and uninduced
      control plants. Infestation densities resulting in the induction of predator
      attractants were much lower than thus far assumed, i.e., predatory mites were
      significantly attracted to plants that were infested for 2 days with only one or
      four spider mites per plant. Phytoseiulus persimilis showed a density-dependent
      response to volatiles from plants that were infested with different numbers of
      spider mites. Similarly, treating plants with increasing concentrations of JA
      also led to increased attraction of P. persimilis. Moreover, the duration of
      spider mite infestation was positively correlated with the proportion of
      predators that were attracted to mite-infested plants. A pretreatment of the
      plants with JA followed by a spider mite infestation enhanced the attraction of
      P. persimilis to plant volatiles compared to attraction to volatiles from plants
      that were only infested with spider mites and did not receive a pretreatment with
      JA. The herbivore, T. urticae preferred leaf tissue that previously had been
      infested with conspecifics to uninfested leaf tissue. In the case of choice tests
      with JA-induced and control leaf tissue, spider mites slightly preferred control
      leaf tissue. When spider mites were given a choice between leaf discs induced by
      JA and leaf discs damaged by spider mite feeding, they preferred the latter. The
      presence of herbivore induced chemicals and/or spider mite products enhanced
      settlement of the mites, whereas treatment with JA seemed to impede settlement.

PMID- 14969354
TI  - Induction of hypericins and hyperforins in Hypericum perforatum in response to
      damage by herbivores.
AB  - Plants respond to herbivore and pathogen attack by a variety of direct and
      indirect mechanisms that include the induction of secondary metabolites. The
      phytomedicinal plant Hypericum perforatum L. produces two different classes of
      secondary metabolites: hyperforins, a family of antimicrobial
      acylphloroglucinols; and hypericins, a family of phototoxic anthraquinones
      exhibiting antimicrobial, antiviral, and antiherbivore properties in vitro. To
      determine whether these compounds are part of the herbivore-specific inducible
      plant defense system, we used an in vitro detached assay to assess the effects of
      specialist and generalist herbivore damage on the levels of hypericins and
      hyperforin. Greenhouse-grown H. perforatum plant sections were challenged with
      the specialist, Chrysolina quadrigemina, or with one of the following generalist
      feeders: Spilosoma virginica, Spilosoma congrua, or Spodoptera exigua. Feeding by
      the specialist beetle or mechanical wounding caused little change in
      phytochemical levels in plant tissue, whereas the small amount of feeding by the
      generalists caused 30-100% increases in hypericins and hyperforin as compared to
      control levels. Although the leaf damage index of the specialist feeding was 2.7
      times greater, C. quadrigemina had little effect on H. perforatum chemical
      defenses in response to feeding damage in comparison to generalist feeding.

PMID- 14969355
TI  - Analysis of a chemical defense in sawfly larvae: easy bleeding targets predatory
      wasps in late summer.
AB  - Contact of certain sawfly larvae with predators frequently elicits an easy
      bleeding behavior involving local disruption of the integument and release of
      hemolymph droplets. The efficacy of this putative antipredator defense was
      investigated in the turnip sawfly, Athalia rosae, by using common garden
      experiments in which particular guilds of predators were excluded, and through
      manipulations of the chemical defense of larval prey. After 3 d of exposure to
      walking and/or flying arthropod predators, the proportion of surviving sawfly
      larvae remained quite high at 71.3% in midsummer, but dropped to 37.5% in late
      summer. However, Pieris rapae caterpillars without the bleeding defense were
      killed within hours by predatory wasps (Vespula vulgaris). Topical treatment of
      P. rapae caterpillars with sawfly hemolymph or sinalbin, a glucosinolate
      sequestered by the sawflies, revealed that the easy bleeding of A. rosae is an
      efficient defense against wasps, partially due to this compound. These
      experiments are the first to demonstrate the efficacy of this chemical defense
      mechanism in a natural setting.

PMID- 14969356
TI  - Structure-activity of valencenoid derivatives and their repellence to the
      Formosan subterranean termite.
AB  - Eight valencenoid derivatives were evaluated for their repelling activity against
      Formosan subterranean termites, Coptotermes formosanus Shiraki. Among them, 1,10
      dihydronootkatone was the strongest repellent, and valencene was the weakest.
      Results of the structure-repellency relationships indicated (1) reduction of the
      ketone group to the alcohol on position 2 of nootkatone curtailed the activity;
      (2) because of the low activity of valencene relative to nootkatone that the
      ketone group was essential for repellent activity; (3) reduction of the 1,10
      double bond (1,10-dihydronootkatone and tetrahydronootkatone) produced compounds
      more repellent than nootkatone; (4) the isopropenyl group probably does not
      participate in binding as evidenced by no significant difference in the repellent
      activity among nootkatone (double bond between position 11 and 12), isonootkatone
      (double bond between position 7 and 11), and 11,12-dihydronootkatone.

PMID- 14969357
TI  - Enhanced invertase activities in the galls of Hormaphis hamamelidis.
AB  - Invertases are sucrose hydrolyzing enzymes often associated with plant tissues
      acting as physiological sinks, and plant galls are physiological sinks. We
      investigated several types of invertase and their potential benefits in galls of
      the aphid Hormaphis hamamelidis. Invertase activities in galls differed from
      those in leaves throughout the growing season. Vacuolar invertase activities (per
      g FW) were always greater in galls than leaves. In contrast, cell wall invertase
      activities per g FW started low in galls, but increased with time and were
      greater than those in leaves after 1 month. Gall growth was most closely related
      to vacuolar invertase activity, whereas leaf growth was correlated with both
      vacuolar and cell wall invertase activities. In separate correlational studies of
      aphid fecundity and invertase activities, cell wall invertase activity per gall
      accounted for 15-21% of the variation in offspring per gall. Gall dry weight
      explained more of the variation in offspring per gall (34.2%) than did gall
      volume (17.8%), a likely indication of the importance of sink strength over the
      life of the gall. Increased invertase activity probably underlies the enhanced
      sink strength commonly observed in galls. Hormaphis hamamelidis fundatrices
      appear to maximize reproductive output by eliciting multiple beneficial responses
      from their hosts. Initial gall growth correlated positively with high vacuolar
      invertase activity, while later in the season aphid fecundity correlated
      positively with cell wall invertase activity.

PMID- 14969358
TI  - The venom alkaloids from some African Monomorium species.
AB  - A comparative analysis of the venom alkaloids of 13 species of ants in the genus
      Monomorium collected in Africa was undertaken. Ants were collected in Kenya and
      South Africa. Most species produced 2,5-dialkylpyrrolidines and some of their
      analogous 1-pyrrolines. No alkaloids were detected in two species. M. robustior
      and M. macrops. Additionally, a novel 2-alkyl-1-pyrroline, whose structure was
      established by synthesis, was detected in M. notulum. This compound and others
      like it may serve as biosynthetic precursors for the formation of the 2,5
      dialkylpyrrolidines found in many Myrmicine ant species.

PMID- 14969359
TI  - Volatile components in metatarsal glands of sika deer, Cervus nippon.
AB  - GC-MS analysis of the metatarsal gland secretion from a female sika deer, Cervus
      nippon, showed 35 major volatile compounds that included 13 straight-chain
      carboxylic acids, a single branched-chain carboxylic acid, 9 straight-chain
      aldehydes, 3 monounsaturated aldehydes, 5 long-chain alcohols, a ketone, and
      cholesterol. The four most abundant compounds were heptanal, nonanal, octanoic
      acid, and 6-methyl-2-heptanone. Many of the compounds have previously been found
      in cervid secretions, but the unsaturated aldehydes, (E)-2-octenal, (E)-2
      nonenal, and (E)-2-decenal, have not previously been reported in the glands of
      any cervid. The compounds in this gland may be pheromones, since metatarsal gland
      odor has been implicated in chemical communication among conspecifics of other
      cervids.

PMID- 14969360
TI  - Field evaluation of plant odor and pheromonal combinations for attracting plum
      curculios.
AB  - The attractiveness of different synthetic host odors and a synthetic aggregation
      pheromone (grandisoic acid [GA]) to overwintered adult plum curculios (PCs),
      Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae), was examined using
      two types of traps (sticky panels and black pyramids) placed in border areas
      surrounding an unsprayed section of an apple orchard in Massachusetts. In 2001,
      we evaluated the response of PCs to three synthetic fruit volatiles (benzaldehyde
      [BEN], ethyl isovalerate [EIV], and limonene [LIM]) assessed alone and in
      combination with GA, as well as the response to GA alone and a no-odor (control)
      treatment. BEN was the only host volatile that synergized the response of PCs to
      GA for both trap types. For both trap types, GA was as attractive to PCs as a
      single component as when in combination with either EIV or LIM. In 2002, four
      release rates of BEN (0, 2.5, 10, and 40 mg/day) and two release rates of GA (1
      and 2 mg/day) were evaluated for attractiveness to PCs using panel and pyramid
      traps. For panel traps, an increase in amount of GA released (from 1 to 2 mg/day)
      was associated with a 35% increase in captures. However, PC captures by pyramid
      traps were similar regardless of the amount of GA released. For panel traps, 10
      and 40 mg/day of BEN were the most attractive release rates regardless of the
      amount of GA released. For pyramid traps baited with GA. PC captures were
      enhanced by the presence of BEN, regardless of release rate. In 2003, GA at 1
      mg/day + BEN at 80 mg/day of release did not enhance PC captures by panel traps
      relative to lower release rates of BEN. Pyramid traps releasing GA at 1 mg/day
      performed best when baited with BEN at 10 mg/day of release; a release rate of 80
      mg/day of BEN decreased the attractiveness of the binary combination of BEN + GA.
      Combined results suggest that BEN at 10 mg/day + GA at 1 mg/day of release
      constitutes an attractive lure that may improve the effectiveness of monitoring
      traps for PCs.

PMID- 14969361
TI  - Pheromone analysis of wild female moths with a PBAN C-terminal peptide injection
      for an estimation of assortative mating in adzuki bean borer, Ostrinia
      scapulalis.
AB  - The adzuki bean borer, Ostrinia scapulalis, has distinct genetic variation in the
      blend of two sex pheromone components, (E)- and (Z)-11-tetradecenyl acetates.
      This variation is largely controlled by a single autosomal locus with two
      alleles, E and Z. E-type (EE) females produce a pheromone with a mean E:Z ratio
      at 99:1 whereas Z-type (ZZ) and I-type (ZE) produce pheromones with mean of 3:97
      and 64:36, respectively. Interestingly, in many natural populations of O.
      scapulalis in Japan, this pheromone polymorphism appears to be stably maintained.
      We tried to predict the changes in relative abundance of each pheromone type by
      estimating the pheromone production genotype of wild females and their male
      mates. The pheromone titer in the wild, mated females was increased without
      changing the blend ratio by an injection of a peptide with pheromone biosynthesis
      activating activity (TKYFSPRL-NH2). The frequencies of E-, I-, and Z-types at
      Matsudo were 15, 52, and 33%, respectively, and did not deviate from the Hardy
      Weinberg expectations. The estimated mating patterns were concordant with the
      assumption that no assortative mating was occurring in this population, and this
      is suggested as a cause of sustained polymorphism at Matsudo.

PMID- 14969362
TI  - Allelochemical potential of Callicarpa acuminata.
AB  - The allelochemical potential of Callicarpa acuminata (Verbenaceae) was
      investigated by using a biodirected fractionation study as part of a long-term
      project to search for bioactive compounds among the rich biodiversity of plant
      communities in the Ecological Reserve El Eden, Quintana Roo, Mexico. Aqueous
      leachate, chloroform-methanol extract, and chromatographic fractions of the
      leaves of C. acuminata inhibited the root growth of test plants (23-70%). Some of
      these treatments caused a moderate inhibition of the radial growth of two
      phytopathogenic fungi, Helminthosporium longirostratum and Alternaria solani (18
      31%). The chloroform-methanol (1:1) extract prepared from the leaves rendered
      five compounds: isopimaric acid (1), a mixture of two diterpenols
      [sandaracopimaradien-19-ol (3) and akhdarenol (4)], alpha-amyrin (5), and the
      flavone salvigenin (6)]. The phytotoxicity exhibited by several fractions and the
      full extract almost disappeared when pure compounds were evaluated on the test
      plants, suggesting a synergistic or additive effect. Compounds (4), (5), and the
      semisynthetic derivative isopimaric acid methyl ether (2) had antifeedant effects
      on Leptinotarsa decemlineata. Compound 5 was most toxic to this insect, followed
      by (2), (4), and (6) with moderate to low toxicity. No correlation was found
      between antifeedant and toxic effects on this insect, suggesting that different
      modes of action were involved. All the test compounds were cytotoxic to insect
      Sf9 cells while (6), (4), and (1) also affected mammalian Chinese Hamster Ovary
      (CHO) cells. Compound 5 showed the strongest selectivity against insect cells.
      This study contributes to the knowledge of the defensive chemistry and added
      value of C. acuminata.

PMID- 14969363
TI  - A siphonotid millipede (Rhinotus) as the source of spiropyrrolizidine oximes of
      dendrobatid frogs.
AB  - Poison frogs of the neotropical family Dendrobatidae contain a wide variety of
      lipophilic alkaloids, which are accumulated from alkaloid-containing arthropods.
      A small millipede, Rhinotus purpureus (Siphonotidae), occurs microsympatrically
      with the dendrobatid frog Dendrobates pumilio on Isla Bastimentos, Bocas del Toro
      Province, Panama. Methanol extracts of this millipede contain the
      spiropyrrolizidine O-methyloxime 236, an alkaloid previously known only from skin
      extracts of poison frogs, including populations of D. pumilio. Thus, R. purpureus
      represents a likely dietary source of such alkaloids in dendrobatid frogs.

PMID- 14969364
TI  - Mandibular pendex spring appliance for use in mixed dentition.
AB  - Loss of space in the mandibular arch is a common occurrence due to several
      different causes such as caries, trauma or iatrogenic damage. This paper
      describes a new TMA spring used in mixed dentition for space regaining in the
      mandibular arch. A clinical report is presented and the advantages of the method
      are discussed.

PMID- 14969365
TI  - Laser pediatric Class II composites utilizing no anesthesia.
AB  - Interproximal lesions can now be restored without local anesthesia and removing
      unnecessary healthy tooth structure. This paper will focus on a new ultra
      conservative technique in Class II composites utilizing the laser, a new
      technique in cavity preparation.

PMID- 14969366
TI  - Alternative rehabilitation treatment for a patient with ectodermal dysplasia.
AB  - The ectodermal dysplasia constitutes a group of hereditary disorders whose
      clinical manifestations can be defects in ectodermal structures. The hypohidrotic
      and anihidrotic are commonly types of ectodermal dysplasia. The main
      characteristics are dental anomalies, hypotrichosis and hypohidrosis. The oral
      rehabilitation of this patients is important for better social living, self
      esteem and oral function. This paper had as objective to relate and discuss a
      case of anihidrotic ectodermal dysplasia, describing the positive influence of an
      alternative rehabilitation treatment.

PMID- 14969367
TI  - Dental implications of Tooth-Nail dysplasia (Witkop syndrome): a report of an
      affected family and an approach to dental management.
AB  - Tooth-Nail dysplasia is a rare genetic disorder, which is classified as an
      ectodermal dysplasia. Diagnostic differentiation from other conditions in this
      category is necessary for effective dental management and genetic counseling. The
      oro-dental and clinical manifestations of Tooth-Nail dysplasia in an affected
      male infant and his father are documented. Other family members have the
      condition and pedigree data are in keeping with autosomal dominant inheritance. A
      comprehensive approach to the dental management of an affected child is proposed.

PMID- 14969368
TI  - Occlusal guidance of two Kabuki make-up syndrome patients: case reports.
AB  - Kabuki make-up syndrome (KMS) has been reported since 1981 by Niikawa et al.
      Complications of KMS were moderate mental retardation, skeletal and
      dermatoglyphic abnormalities. A 7 year-old boy, who had severe permanent tooth
      deficiency, anterior open bite, tongue thrust and mild mental retardation, was
      referred to our clinic. Oral characters of another patient were an anterior open
      bite, transposition of maxillary central and lateral incisor. Orthodontic
      treatment in two patients is reported and suggested future treatment plans in
      these patients is given.

PMID- 14969369
TI  - Biological factors in dental caries enamel structure and the caries process in
      the dynamic process of demineralization and remineralization (part 2).
AB  - Dental caries is a complex disease process that afflicts a large proportion of
      the world's population, regardless of gender, age and ethnicity, although it does
      tend to affect more indivduals with a low socioeconomic status to a greater
      extent. The physicochemical properties of the mineral comprising the tooth
      surface and subsurface modulate the development, arrestment and remineralization
      of dental caries. Post-eruption maturation of enamel surfaces and exposed root
      surfaces is important in order for more susceptible mineral phases to be modified
      by incorporation of soluble fluoride from the plaque into dental hydroxyapatite.
      The chemical reactions that occur during acidic conditions when tooth mineral
      dissolves (critical pH) are determined by the supersaturation of calcium and
      phosphate within plaque and saliva, as well as if fluoride is present.

PMID- 14969370
TI  - Comparative clinical evaluation of slot versus dovetail Class III composite
      restorations in primary anterior teeth.
AB  - This study compares the clinical characteristic evaluations of slot against
      dovetail class III composite restorations. Focusing on the primary anterior teeth
      of children aged 2 years 6 months to 5 years 3 months with the mean age of 4
      years, thirty-six matched pairs of class III of slot and dovetail preparations
      were made by one investigator These preparations were evaluated for marginal
      adaptation, anatomic form, secondary caries and marginal discoloration after 6,
      12, and 24 months by another investigator with the intra-examiner reliability of
      0.95 - 1 (Kappa Statistic). The results revealed no statistical significance in
      the difference of clinical characteristics between the two designs (p > 0.05).

PMID- 14969371
TI  - The relationship between tongue-base position and craniofacial morphology in
      preschool children.
AB  - The association between tongue-base position and craniofacial morphology was
      investigated in 35 preschool children (17 girls and 18 boys), 3 to 6 years of
      age, by the lateral cephalometric radiographs. There was no statistical
      difference in the measurements of those between girls and boys. Posterior facial
      height, nasal floor length, mandibular corpus length and tongue-base position
      were positively correlated with age, and tongue-base position was correlated with
      maxillary position, vertical mandibular rotation and the nasopharyngeal airway
      space. The results of this study showed that tongue-base position influenced
      maxillo-mandibular growth even in young preschool children.

PMID- 14969372
TI  - Relationship between mandibular deviation and ocular convergence.
AB  - Recent studies have confirmed the relationship between head posture, mandibular
      position and visual focusing. A case-controlled study was conducted to assess the
      occurrence of ocular convergence defects between subjects with functional
      mandibular latero-deviation and healthy subjects in pediatric age. Sixty subjects
      (the study group) presented mandibular latero-deviation classified as functional
      according to the use of a clinical examination and frontal and basal tele
      radiography. Sixty subjects without functional mandibular laterodeviation
      (control group) were selected randomly from all subjects seeking pediatric dental
      care and matched by gender and age to study group. All one hundred and twenty
      subjects were submitted to orthoptic tests performed by the same operator. These
      results seemed to confirm that in mandibular latero-deviation subjects ocular
      convergence defects occurred in greater frequency than in controls underlining
      the importance of role of pediatric dentistry among interdisciplinary
      cooperation.

PMID- 14969373
TI  - Maximum bite force and related dental status in children with deciduous
      dentition.
AB  - Six hundred seventy-six Taiwanese children with deciduous dentition were sampled
      for maximum bite force and related dental status. Sixty-seven percent of children
      had at least one decayed tooth. The mean number of decayed teeth of all children
      was 2.97+/-3.58, and the mean plaque index of the right maxillary central incisor
      was 2.00+/-0.75. Twenty-seven percent of children had occlusal anomalies. Boys
      had a statistically significantly larger maximum bite force than did girls.
      Children with normal occlusion had statistically significantly larger maximum
      bite forces than did children with malocclusion. A statistically positive
      correlation was found between the number of decayed teeth and the plaque index.
      However, a statistically negative correlation was found between the number of
      decayed teeth and the maximum bite force and between the plaque index and the
      maximum bite force.

PMID- 14969374
TI  - Esthetic alternative for fluorosis blemishes with the usage of a dual bleaching
      system based on hydrogen peroxide at 35%.
AB  - Esthetic dental procedures in pediatric dentistry represent sources of
      satisfaction and realization, as much for the patient as for the professional.
      Lack of dental esthetics may develop psychological problems in infant as well as
      in adolescent patients. Blemishes produced by fluorosis appear as a challenge to
      the pediatric dentist and alternatives for treatment are desired. The scope of
      this present paper is to relate a clinical case with esthetic solution for
      blemishes in teeth enamel due to fluorosis. A dual system of bleaching was used
      (photo/chemically activated) based on hydrogen peroxide at 35% (Hi-Lite-Shofu) in
      a male eight-year-old patient with white fluorosis blemishes on teeth 11 and 21.
      The bleaching system used was efficient in bleaching teeth with white blemishes
      due to fluorosis, thus masking the blemishes and providing a more uniform
      appearance.

PMID- 14969375
TI  - Behavior of partially formed roots of teeth submitted to orthodontic movement.
AB  - The occurrence of root resorption in orthodontically treated permanent incisors
      with partially formed roots was investigated using periapical radiographs taken
      before and after the orthodontic leveling in the mixed dentition. The mean age at
      the beginning of treatment was 9 years and the mean treatment time was 7.1
      months. The findings showed that the orthodontic movement during root formation
      causes no root resorption. The longitudinal follow-up showed that incompletely
      formed roots developed normally.

PMID- 14969376
TI  - Factors influencing the use of behavioral management techniques during child
      management by dentists.
AB  - Dental anxiety develops from a vicious cycle of bodily arousal from dental
      stimuli, cognitive interpretation and ineffective coping all working in a runaway
      feedback loop. Behavioral management strategies (BMT) aim at cognitive
      reorientation, which results in better compliance with instruction. This paper
      therefore tried to find out possible factors that influence the effective use of
      BMT during child dental management during treatment by dental operators in
      Nigeria. The levels of anxiety pre and post treatment were assessed using the
      short form of the dental version of the Child Fear Survey Schedule. Also, the
      type of treatment given to the child, the types and number of behavioral
      strategies employed during dental management as well as the gender and age of the
      child were noted. The professional status of the attending dental operator was
      also noted. Prior to the commencement of the study, the five students in the
      final year, who were to attend to the children in this study received one week
      training on the psychological management of dental anxiety in children. Results
      obtained from the dental operators were compared. The type of treatment received
      by the child did not significantly affect the dental anxiety score. The number of
      techniques combined by house officers and senior registrars were significantly
      higher than would be expected by chance (chi2=16.030, P=0.0001 and chi2=9.000,
      P=0.0001 respectively). Combination of techniques was also more frequent during
      invasive procedures and when dental anxiety levels were high. Combining
      techniques also tended to decrease dental anxiety more significantly than
      otherwise. Training has a role to play in the basic and efficient use in the
      management of the child dental patient. The training of dentists should thus
      entail the full spectrum (content and instructional effectiveness) of all
      psychological techniques.

PMID- 14969377
TI  - Tongue scraping as a means of reducing oral mutans streptococci.
AB  - Mutans streptococci (MS) are one of the most virulent cariogenic pathogens in the
      oral cavity. The effects of three oral hygiene techniques on salivary mutans
      streptococci levels were evaluated to see which mechanism would be most efficient
      in reducing salivary MS levels. Sixty patients, all in the permanent dentition,
      were selected and randomly distributed into three groups. Group I was asked to
      use a tongue scraper to brush the tongue once daily in the morning after normal
      tooth brushing routine. Group II was asked to place and let dissolve a Listerine
      Oral Care Strip on the tongue once daily after normal oral hygiene routine. Group
      III was asked to rinse once every morning, for thirty seconds, with a saturated
      saline solution after routine tooth brushing. The instructions were done for a
      period of seven days. Baseline, one hour, three day, and seven day saliva samples
      were obtained and plated on CRT" by Vivadent MS-sensitive agar. All treatments
      groups show a significant reduction in colony counts from baseline and one or
      more post treatment periods and at one or more time periods between treatment
      groups. The most effective treatment in reducing colony counts was seen within
      Group I "Tongue Scraping" which demonstrated the greatest change from baseline to
      each of the post treatment periods. The least effective was Group II "Listerine
      Strip" which showed a statistically insignificant increase in colony count from
      baseline to 1-Hour and a significant decrease from baseline at the 7-day period
      only.

PMID- 14969378
TI  - Primitive neuroectodermal tumor in the jaw: report of a case.
AB  - The neuroectodermal tumor is a malignant neoplasm of round cells originated from
      the neural crest. The occurrence of this tumor in head and neck is rare. A 5
      month old Mexican patient with a primitive neuroectodermic tumor stage IV, in the
      jaw is reported.

PMID- 14969379
TI  - Crouzonodermoskeletal syndrome.
AB  - Crouzon craniostenosis [MIM 123500], is identified on the basis of the additional
      phenotypical manifestations of acanthosis nigricans, vertebral changes and
      cementomas of the jaws. Choanal atresia and hydrocephalus are other features. The
      molecular defect in CDSS is a point mutation in the FGFR3 gene on chromosome 4p,
      whereas, the mutation in the Crouzon syndrome is in the FGFR2 gene at 10q25.3-26.
      An affected girl aged 2 years presented at the UWC dental genetics unit with a
      prior diagnosis of Crouzon syndrome. Choanal atresia had necessitated a permanent
      tracheostomy, and hydrocephalus was managed by a shunt operation. Clinical
      examination revealed acanthosis nigricans in the axilliary regions, a diagnosis
      confirmed by a biopsy of the lesion. Eruption of the primary dentition was
      delayed with only six out of twenty teeth present. Radiographic examination
      conducted shortly after birth revealed the presence of several tooth buds in both
      the maxillae and the mandible. The delayed eruption of the teeth will be of
      significance in future orthodontic and maxillofacial measures for the improvement
      of the patient's facial Crouzonodermoskeletal syndrome (CDSS) was separated from
      the classical appearance. Molecular investigations in the girl and her parents
      are underway. If the specific mutation in FGFR3 is observed, a positive diagnosis
      of CDSS will be confirmed and the status of her parents and other family members
      will be determined. On this basis, appropriate genetic management can be offered
      to the kindred.

PMID- 14969380
TI  - Bilateral dentigerous cyst associated with polymorphism in chromosome 1qh+.
AB  - Non-syndromal bilateral dentigerous cysts are rare. It is conceivable that they
      are either under-recognized or under-reported. In this article we report the
      unusual occurrence of non-syndromic bilateral dentigerous cysts associated with
      mandibular third molars with polymorphism in chromosome 1qh+. It is suggested
      that in non syndromal cases of bilateral dentigerous cysts karyotyping should be
      done to confirm the association with chromosomal 1 anomaly.

PMID- 14969381
TI  - Eruption cysts: a clinical report of 24 new cases.
AB  - The eruption cyst (EC) occurs within the mucosa overlying a tooth that is about
      to erupt. In the past EC was considered a type of dentigerous cyst (DC) occuring
      in the soft tissues. Twenty four patients (mean age 4.44 years, range 1.0 month
      12 years) with EC were diagnosed and treated. EC was associated with natal teeth
      in two (8.3%) cases, with primary teeth in 10 (41.6%) cases and with permanent
      teeth in 12 (50%) cases. There was a gender predilection, the male to female
      ratio was 2:1. The primary mandibular central incisors and the permanent first
      molars were the most common site affected. The clinical appearance was a raised,
      bluish gingival mass on the alveolar ridge. The size was variable and dependent
      on the size and number of the associated teeth. The type of treatment provided
      was one of the following: no treatment (10 cases, 42%), extraction (2 cases, 8%)
      and marsupialization (12 cases, 50%). All surgical specimens underwent
      histopathologic examination. EC should be recognized as a separate entity from DC
      and a conservative treatment approach is recommended.

PMID- 14969382
TI  - Extinction and permanence of a two-prey one-predator system with impulsive
      effect.
AB  - In this paper, we investigate a two-prey one-predator system with impulsive
      effect on the predator of fixed moment. By using Floquet's theorem and small
      amplitude perturbation skills, we show that there exists a globally
      asymptotically stable two-pest eradication periodic solution when the impulsive
      period is less than some critical value. Further, we prove that the system is
      permanent if the impulsive period is larger than some critical value, and
      meanwhile the conditions for the extinction of one of the two prey and permanence
      of the remaining two species are given. Finally, numerical simulation shows that
      there exists a stable positive periodic solution with a maximum value no larger
      than a given level. Therefore, we can use the stability of the positive periodic
      solution and its period to control insect pests at acceptably low levels.

PMID- 14969383
TI  - Exact test of Hardy-Weinberg equilibrium by Markov chain Monte Carlo.
AB  - The assumption of Hardy-Weinberg equilibrium (HWE) among alleles is of
      fundamental importance in genetic studies. There are numerous testing methods for
      it using genotype counts data. The exact test is used when the sample size is not
      large enough for asymptotic approximations. There are several numerical methods
      to carry out this test, such as complete enumeration, Monte Carlo and Markov
      chain Monte Carlo simulations. Complete enumeration is impractical in many
      applications, especially when the table counts are large. The Monte Carlo method
      is simple to use but still difficult when the table counts become large. The
      Markov chain Monte Carlo method, by sampling a sub-table each time, is suitable
      for this latter situation. Based on switches among a few (no more than four)
      cells, the existing Markov chain samplers are highly dependent and inefficient
      for large tables. Here we consider a new Markov chain sampling, in which a sub
      table of user-specified size is updated at each iteration. The resulting chain is
      less dependent, and the sampling is flexible and efficient. The conventional test
      for HWE is based on a few test statistics, such as the likelihood and the chi
      squared statistic. To expand the family of test statistics, we consider a class
      of divergence measures for the departure of HWE. Examples are given as
      illustrations.

PMID- 14969384
TI  - Modelling solid tumour growth using the theory of mixtures.
AB  - In this paper the theory of mixtures is used to develop a two-phase model of an
      avascular tumour, which comprises a solid, cellular, phase and a liquid phase.
      Mass and momentum balances which are used to derive the governing equations are
      supplemented by constitutive laws that distinguish the two phases and enable the
      stresses within the tumour to be calculated. Novel features of the model include
      the dependence of the cell proliferation rate on the cellular stress and the
      incorporation of mass exchange between the two phases. A combination of numerical
      and analytical techniques is used to investigate the sensitivity of equilibrium
      tumour configurations to changes in the model parameters. Variation of parameters
      such as the maximum cell proliferation rate and the rate of natural cell death
      yield results which are consistent with analyses performed on simpler tumour
      growth models and indicate that the two-phase formulation is a natural extension
      of the earlier models. New predictions relate to the impact of mechanical effects
      on the tumour's equilibrium size which decreases under increasing stress and/or
      external loading. In particular, as a parameter which measures the reduction in
      cell proliferation due to cell stress is increased a critical value is reached,
      above which the tumour is eliminated.

PMID- 14969385
TI  - Improved leaf area index based biomass estimations for Zostera marina L.
AB  - The application of special scanning technologies in plant population studies
      makes it now possible to offer reliable indirect estimations of Leaf Area Index
      (LAI). This has stimulated the adaptation of related biomass assessment methods
      and has provided a way to simplify tedious laboratory procedures whilst avoiding
      destructive sampling. Particularly, above-ground biomass for Zostera marina L.
      has been expressed depending linearly on Leaf Area Index. Nevertheless, we
      demonstrate that this approach produces biased estimations. It is also shown that
      expressing leaf dry weight by means of an allometric function of length and width
      can eliminate bias. Furthermore, the dominant term of the associated power series
      expansion becomes the aforementioned linear representation in terms of Leaf Area
      Index. The consistency of the estimation methods derived from the allometric
      model was tested using data from a Z. marina meadow. Consequently, the improved
      method is expected to become a valuable tool for the reduction of the uncertainty
      associated with the estimation of above-ground biomass through the use of Leaf
      Area Index.

PMID- 14969386
TI  - PTH/PTHrP activity and the programming of skeletal development in utero.
AB  - There is increasing evidence that nutritional deficiency in utero adversely
      affects bone development and the risk of developing osteoporosis in later life.
      Although the mechanisms involved are unknown, circumstantial evidence points to
      an important role of PTH/PTHrP activity. It is recognized that PTH and PTHrP are
      critically involved in regulating fetal calcium homeostasis, actions that are
      mediated at least in part by PPR. As well as playing a central role in the
      maintenance of calcium homeostasis in the fetus, studies in transgenic mice show
      that PTH, PTHrP, and PPR exert similar effects on skeletal development in utero,
      acting to increase the size of the trabecular envelope and decrease that of the
      cortical envelopes. Taken together, these observations raise the possibility that
      stimulation of PTH/PTHrP activity in the fetus in response to calcium deficiency
      acts to increase the size of the trabecular envelope but to reduce that of the
      cortical envelope. Although any increase in trabecular bone at birth is likely to
      be relatively transient, a decrease in size of the cortical envelope may have a
      persistent effect on the trajectory of bone growth in subsequent childhood.
      Consistent with this proposal, preliminary findings from birth cohort studies
      suggest that maternal calcium intake and cord blood calcium levels are positively
      related to bone mass of the offspring as assessed later in childhood. Further
      studies are justified to determine whether alterations in fetal PTH/ PTHrP
      activity caused by calcium stress lead to a reduction in size of the cortical
      envelope at birth that persists into childhood and later adult life and to
      identify modifiable maternal factors that are responsible for these changes.

PMID- 14969387
TI  - Localization of the gene causing the osteopetrotic phenotype in the incisors
      absent (ia) rat on chromosome 10q32.1.
AB  - The incisors absent rat is an osteopetrotic animal model. Segregation analysis in
      37 affected animals from an outcross enabled us to assign the disease causing
      gene to a 4.7-cM interval on rat chromosome 10q32.1. Further analysis of the
      genes mapped in this region will provide more insight into the underlying
      pathogenesis. INTRODUCTION: Many of the insights into the factors that regulate
      the differentiation and activation of osteoclasts are gained from different
      spontaneous and genetically induced osteopetrotic animal models. The
      osteopetrotic incisors absent (ia) rat exhibits a generalized skeletal sclerosis
      and a delay of tooth eruption. Although the ia rat has well been studied
      phenotypically, the genetic defect still remains unknown. MATERIAL AND METHODS:
      To map the ia locus, we outcrossed the inbred ia strain with the inbred strain
      Brown Norway. Intercrossing F1 animals produced the F2 generation. Thirty-one
      mutant F2 animals and six mutant F4 animals were available for segregation
      analysis. RESULTS: Segregation analysis enabled us to assign the disease causing
      gene to rat chromosome 10q32.1. Homozygosity for the ia allele was obtained for
      two of the markers analyzed (D10Rat18 and D10Rat84). Key recombinations delineate
      a candidate region of 4.7 cM flanked by the markers D10Rat99 and D10Rat17.
      CONCLUSION: We have delineated a 4.7-cM region on rat chromosome 10q32.1 in which
      the gene responsible for the osteopetrotic phenotype of the ia rat is located.
      Although the sequence of this chromosomal region is not complete, over 140 known
      or putative genes have already been assigned to this region. Among these, several
      candidate genes with a putative role in osteoclast functioning can be identified.
      However, at this point, it cannot be excluded that one of the genes with a
      currently unknown function is involved in the pathogenesis of the ia rat. Further
      analysis of the genes mapped in this region will provide us more insight into the
      pathogenesis of this osteopetrotic animal model.

PMID- 14969388
TI  - Osteoclastic potential of human CFU-GM: biphasic effect of GM-CSF.
AB  - Human osteoclasts can be efficiently generated in vitro from cord blood
      mononuclear cells and derived CFU-GM colonies. However, CFU-M colonies are poorly
      osteoclastogenic. Short-term (2-48 h) treatment with GM-CSF stimulates osteoclast
      formation by proliferating precursors, whereas longer exposure favors dendritic
      cell formation. INTRODUCTION: Osteoclasts (OC) differentiate from cells of the
      myelomonocytic lineage under the influence of macrophage-colony stimulating
      factor (M-CSF) and RANKL. However, cells of this lineage can also differentiate
      to macrophages and dendritic cells (DC) depending on the cytokine environment.
      The aims of this study were to develop an efficient human osteoclastogenesis
      model and to investigate the roles of granulocyte macrophage-colony stimulating
      factor (GM-CSF) and M-CSF in human OC differentiation. MATERIALS AND METHODS: A
      human osteoclastogenesis model, using as precursors colony forming unit
      granulocyte macrophage (CFU-GM) colonies generated from umbilical cord
      mononuclear cells cultured in methylcellulose with GM-CSF, interleukin (IL)-3 and
      stem cell factor (SCF), has been developed. CFU-GM, colony forming unit
      macrophage (CFU-M), or mixed colonies were cultured on dentine with soluble RANKL
      (sRANKL) and human M-CSF with and without GM-CSF. Major endpoints were OC number,
      dentine resorption, and CD1a+ DC clusters. RESULTS: Osteoclast generation from
      CFU-GM and mixed colonies treated with M-CSF and sRANKL for 7-14 days was highly
      efficient, but CFU-M colonies were poorly osteoclastogenic under these
      conditions. Pretreatment of precursors with M-CSF for 7 or 14 days maintained the
      precursor pool, but OCs were smaller and resorption was reduced. The effect of GM
      CSF treatment was biphasic, depending on the timing and duration of exposure.
      Short-term treatment (2-48 h) at the beginning of the culture stimulated cell
      proliferation and enhanced OC formation up to 100%, independent of sRANKL. Longer
      term GM-CSF treatment in the presence of sRANKL, however, inhibited OC generation
      with the formation of extensive CD1a+ DC clusters, accompanied by downregulation
      of c-Fos mRNA. Delaying the addition of GM-CSF resulted in progressively less
      inhibition of osteoclastogenesis. CONCLUSIONS: Human CFU-GM, but not CFU-M,
      progenitors have high osteoclastogenic potential. GM-CSF plays an important role
      in osteoclastogenesis and has a biphasic effect: Short-term treatment potentiates
      OC differentiation by proliferating precursors, but persistent exposure favors DC
      formation.

PMID- 14969389
TI  - Estrogen regulates the production of VEGF for osteoclast formation and activity
      in op/op mice.
AB  - Op/op mice have a severe deficiency of osteoclasts because of lacking functional
      M-CSF that is an essential factor of osteoclast differentiation and function. We
      now report that OVX induces osteoclast formation and cures osteopetrosis by
      increasing the VEGF that regulates osteoclast formation in these mice.
      INTRODUCTION: We have found that estrogen deficiency induced by ovariectomy (OVX)
      upregulated osteoclast formation in op/op mice. We have recently demonstrated
      that vascular endothelial growth factor (VEGF) could substitute for macrophage
      colony-stimulating factor (M-CSF) in the support of osteoclastic bone resorption
      in these mice. Therefore, in this study, we wished to assess the effects of VEGF
      on bone loss induced by OVX in these mice. MATERIALS AND METHODS: Eight-week-old
      op/op mice were bilateral OVX or sham-operated. Mice were killed at 8, 10, and 12
      weeks of age, and femurs were removed for preparations. Some OVX mice were
      treated with three consecutive injections of 120 microl/body of VEGF-neutralizing
      antibody at 12-h intervals starting from 36 h before death at 4 weeks after OVX.
      VEGFR-1/Fc chimeric protein (600 microg/kg/day) or 17beta-estradiol (0.16
      microg/day) was administered in a dorsal subcutaneous pocket of the mice at the
      time of OVX. These mice were killed 2 weeks after surgery. Changes of serum
      levels of VEGF were measured by ELISA. Changes of mRNA levels of VEGF, Flt-1,
      interleukin-6, and osteoclast differentiation factor (ODF/TRANCE/RANKL) in bone
      tissue were measured by reverse transcriptase-polymerase chain reaction. RESULTS:
      In OVX op/op mice, trabecular bone volume of the femur was decreased, and the
      number of osteoclasts was significantly increased. Serum levels of VEGF were
      demonstrated to be higher in OVX mice than in sham-operated mice. VEGF mRNA, Flt
      1 mRNA, interleukin-6 mRNA, and RANKL mRNA levels in bone tissue were elevated in
      OVX mice over that in sham-operated mice. The increase in osteoclast number was
      inhibited by VEGF antagonist treatment in OVX mice. CONCLUSIONS: In this study,
      we have demonstrated that the production of VEGF and RANKL stimulated by OVX
      results in increased osteoclast formation in op/op mice.

PMID- 14969390
TI  - RANK signaling is not required for TNFalpha-mediated increase in CD11(hi)
      osteoclast precursors but is essential for mature osteoclast formation in
      TNFalpha-mediated inflammatory arthritis.
AB  - To address the controversy of whether TNFalpha can compensate for RANKL in
      osteoclastogenesis in vivo, we used a TNFalpha-induced animal model of
      inflammatory arthritis and blocked RANKL/RANK signaling. TNFalpha increased
      osteoclast precursors available for RANK-dependent osteoclastogenesis. RANK
      signaling is not required for the TNFalpha-stimulated increase in CD11b(hi)
      osteoclast precursors but is essential for mature osteoclast formation.
      INTRODUCTION: Although critical roles of TNFalpha in inflammatory arthritis and
      RANKL in bone resorption have been firmly established, a central controversy
      remains about the extent to which TNFalpha can compensate for RANKL during
      osteoclastogenesis and the stage at which RANK signaling is required for
      osteoclastogenesis. Here, we used the human TNFalpha transgenic mouse model (TNF
      Tg) of erosive arthritis to determine if there are both RANK-dependent and 
      independent stages of osteoclastogenesis in TNFalpha-induced erosive arthritis.
      MATERIALS AND METHODS: Osteoclastogenesis and osteoclast precursor (OCP)
      frequency were analyzed using histology, fluorescence-activated cell sorting
      (FACS), and cell culture from (1) TNF-Tg mice treated with the RANKL antagonist,
      RANK:Fc, or (2) TNF-Tg X RANK -/- mice generated by crossing TNF-Tg mice with
      RANK-/- mice. RESULTS: Treatment of TNF-Tg mice, which have increased OCPs in
      their spleens, with RANK:Fc dramatically reduced osteoclast numbers on the
      surface of their arthritic joints and within their bones, but did not decrease
      CD11b(hi) OCP numbers in their spleens. Long-term RANK:Fc administration
      alleviated joint erosion. Furthermore, TNF-Tg x RANK -/- mice had severe
      osteopetrosis, no osteoclasts, and no joint erosion, but increased CD11b(hi)
      precursor numbers that failed to form mature osteoclasts in vitro. CONCLUSION:
      RANK signaling is essential for mature osteoclast formation in TNFalpha-mediated
      inflammatory arthritis but not for the TNFalpha-induced increase in CD11b(hi) OCP
      that subsequently can differentiate into osteoclasts in inflamed joints.

PMID- 14969391
TI  - Deficiency of insulin receptor substrate-1 impairs skeletal growth through early
      closure of epiphyseal cartilage.
AB  - Morphological analyses in and around the epiphyseal cartilage of mice deficient
      in insulin receptor substrate-1 (IRS-1) showed IRS-1 signaling to be important
      for skeletal growth by preventing early closure of the epiphyseal cartilage and
      maintaining the subsequent bone turnover at the primary spongiosa. INTRODUCTION:
      IRS-1 is an essential molecule for intracellular signaling by IGF-I and insulin,
      both of which are potent anabolic regulators of cartilage and bone metabolism. To
      clarify the role of IRS-1 signaling in the skeletal growth, morphological
      analyses were performed in and around the epiphyseal cartilage of mice deficient
      in IRS-1 (IRS-1(-/-)), whose limbs and trunk were 20-30% shorter than wildtype
      (WT) mice. MATERIALS AND METHODS: The epiphyseal cartilage and the primary
      spongiosa at proximal tibias of homozygous IRS-1(-/-) and WT male littermates
      were compared using histological, immunohistochemical, enzyme cytohistochemical,
      ultrastructural, and bone histomorphometrical analyses. RESULTS: In and around
      the WT epiphyseal cartilage, IRS-1 and insulin-like growth factor (IGF)-1
      receptors were widely expressed, whereas IRS-2 was weakly localized in bone
      cells. Chronological observation revealed that height of the proliferative zone
      and the size of hypertrophic chondrocytes were decreased in WT mice as a function
      of age, and these decreases were accelerated in the IRS-1 (-/-) cartilage, whose
      findings at 12 weeks were similar to those of WT at 24 weeks. In the IRS-1(-/-)
      cartilage, proliferating chondrocytes with positive proliferating cell nuclear
      antigen (PCNA) or parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor
      immunostaining had almost disappeared by 12 weeks. Contrarily, TUNEL+ apoptotic
      cells were increased in the hypertrophic zone, at the bottom of which most of the
      chondrocytes were surrounded by the calcified matrix, suggesting the closure of
      the cartilage. In the primary spongiosa, bone volume, alkaline phosphatase (ALP)+
      osteoblasts, TRACP+ osteoclasts, and the osteopontin-positive cement line were
      markedly decreased. Bone histomorphometrical parameters for both bone formation
      and resorption were significantly lower in IRS-1(-/-) mice, indicating the
      suppression of bone turnover. CONCLUSION: The IRS-1(-/-) epiphyseal cartilage
      exhibited insufficient proliferation of chondrocytes, calcification of
      hypertrophic chondrocytes, acceleration of apoptosis, and early closure of the
      growth plate. Thus, the data strongly suggest that IRS-1 signaling is important
      for the skeletal growth by preventing early closure of the epiphyseal cartilage
      and by maintaining the subsequent bone turnover at the primary spongiosa.

PMID- 14969392
TI  - The signaling adapter protein DAP12 regulates multinucleation during osteoclast
      development.
AB  - Deficiency of the signaling adapter protein DAP12 is associated with bony
      abnormalities in both mice and humans. We identify specific DAP12-associated
      receptors expressed by osteoclasts and examine function of DAP12 in murine
      osteoclasts in vivo and in vitro. These data show a new role for DAP12 signaling
      in regulating formation of multinucleated osteoclasts. INTRODUCTION: Osteoclasts
      are bone-resorbing cells derived from hematopoietic precursors in the myeloid
      lineage. In other myeloid cell types, the signaling adapter protein DAP12
      transmits activating signals on ligation of a DAP12-associated receptor (DAR).
      The aim of this study was to clarify the role of DAP12 signaling during
      osteoclast development. MATERIALS AND METHODS: Osteoclasts from DAP12 -/- or
      control mice were analyzed in vitro for morphology, function, and for osteoclast
      markers. DARs were identified in osteoclast cultures through reverse
      transcriptase-polymerase chain reaction (RT-PCR). Bone density of DAP12 -/- and
      control mice were analyzed by microcomputed tomography. DAP12 -/- osteoclasts
      were retrovirally reconstituted with DAP12. RAW264.7 cells were transfected with
      FLAG-tagged DAP12 or TREM2 and stimulated by anti-FLAG antibody during in vitro
      osteoclastogenesis. RESULTS: C57BL/6 DAP12-deficient mice have higher bone mass
      than C57BL/6 wildtype controls. We verified the presence of DAP12 in pre
      osteoclasts and osteoclasts derived from C57BL/6 or the pre-osteoclast line RAW
      264.7 and identified the DARs expressed. DAP12 -/- osteoclasts developed in vitro
      with macrophage colony-stimulating factor (M-CSF) and RANKL formed only intensely
      TRACP+ mononuclear cells and failed to generate multinuclear osteoclasts. These
      mononuclear cells are functional osteoclast-like cells because, by RT-PCR, they
      express other osteoclast markers and generate resorption pits on dentine slices,
      although quantitative assessment of bone resorption shows decreased resorption by
      DAP12 -/- osteoclasts compared with C57BL/6 osteoclasts. Restoration of DAP12
      expression by retroviral transduction of DAP12 -/- osteoclast precursors rescued
      in vitro osteoclast multinucleation. Direct stimulation of DAP12 expressed in
      RAW264.7 during in vitro osteoclastogenesis led to a marked increase in the
      number of TRACP+ multinucleated osteoclast-like cells formed. CONCLUSION: Our
      studies indicate that stimulation of the DAP12 adapter protein plays a
      significant role in formation of multinuclear osteoclasts and that DAP12 and DARs
      likely participate in the regulation of bony remodeling.

PMID- 14969393
TI  - PTH differentially regulates expression of RANKL and OPG.
AB  - RANKL and OPG gene expressions were measured with and without PTH at different
      stages of osteoblast development. Mouse stromal cells were cultured in osteoblast
      differentiating conditions, and RANKL, OPG, COLI, ALP, OC, and PTHRec genes were
      measured using qRT-PCR. OPG:RANKL ratios indicate that PTH may induce a possible
      switch in the regulatory mechanism of osteoclastogenesis where OPG is inhibited
      early and RANKL is increased at late stages of osteoblast differentiation.
      INTRODUCTION: RANKL is essential for osteoclastogenesis, and its decoy receptor
      osteoprotegerin (OPG) negatively regulates this process. Both genes are expressed
      in cells of the osteoblast lineage, but the precise relationship between the
      state of osteoblast differentiation and RANKL and OPG expression is not clearly
      defined. The goal of this project was to quantify changes in RANKL and OPG gene
      expression in response to parathyroid hormone (PTH) at different stages of
      osteoblast differentiation. In this study, mouse primary bone marrow stromal
      cells (BMSCs) were cultured for up to 28 days. At specific time-points of cell
      culture, cells were stimulated with bovine PTH peptide [bPTH (1-34)] for 2 h.
      Levels of RANKL, OPG, alpha-1 (type I) collagen (COL1), alkaline phosphatase
      (ALP), osteocalcin (OC), and PTH receptor (PTHRec) mRNA were assayed using
      quantitative real-time reverse-transcriptase-polymerase chain reaction (qRT-PCR).
      MATERIALS AND METHODS: In control cells, there was a gradual increase of RANKL
      gene expression with murine osteoblastic stromal cell maturation to a 3-fold
      level at day 28. In contrast, OPG mRNA levels were maximal at day 14 of cell
      culture and decreased through the latter stages of osteoblast differentiation.
      Exposing the cells to 100 ng/ml of bPTH (1-34) induced minimal increases in RANKL
      mRNA levels from days 7 to 14 but elevated expression significantly at days 21 (2
      fold) and 28 (3-fold). PTH inhibited OPG gene expression maximally at day 14, but
      continued to have inhibitory effects on cultured cells at days 21 and 28.
      Alterations of RANKL and OPG mRNA levels by PTH in day 14 osteoblasts were
      sufficient to sustain a 5.6-fold increase in the number of TRACP+ cells when
      cocultured with osteoclast precursor cells. Cells in culture after 28 days showed
      a 1.9-fold increase in TRACP+ cells after PTH treatment. RESULTS AND CONCLUSIONS:
      We conclude that (1) PTH significantly upregulates RANKL mRNA in primary bone
      marrow stromal osteoblasts with maximal sensitivity occurring late in osteoblast
      differentiation; (2) PTH inhibits OPG gene expression at all stages of osteoblast
      differentiation; and (3) changes in RANKL and OPG mRNA levels after exposure to
      PTH are associated with increased osteoclastogenesis as demonstrated by increased
      numbers of TRACP+ cells in cocultures. The results further suggest that the
      osteoclastogenic activity of PTH occurs primarily by suppression of OPG gene
      expression in early osteoblasts and elevation of RANKL gene expression in mature
      osteoblasts.

PMID- 14969394
TI  - Negative regulation of chondrocyte differentiation by transcription factor AP
      2alpha.
AB  - This study investigated the role of transcription factor AP-2alpha in chondrocyte
      differentiation in vitro. AP-2alpha mRNA declined during differentiation, and
      overexpression of AP-2alpha inhibited differentiation. The results demonstrated
      that AP-2alpha plays a negative role in chondrocyte differentiation.
      INTRODUCTION: Transcription factor AP-2alpha has been detected in growth plate
      and articular chondrocytes and has been shown to regulate cartilage matrix gene
      expression in vitro. However, the precise functional role of AP-2alpha in
      chondrocyte differentiation is not known. In this study, we assessed the
      expression and the function of AP-2alpha in chondrocyte differentiation of ATDC5
      cells. MATERIALS AND METHODS: Chondrocyte differentiation of ATDC5 cells was
      induced with insulin or transforming growth factor beta (TGF-beta). Proteoglycan
      production was assessed by alcian blue staining, and expression levels of
      chondrocyte marker genes and AP-2 gene family were determined by quantitative
      real time reverse transcriptase-polymerase chain reaction (RT-PCR).
      Overexpression of AP-2alpha in ATDC5 cells was accomplished by retroviral
      infection. Infected cells were selected for G418 resistance and pooled for
      further analysis. RESULTS AND CONCLUSIONS: Quantitative real time RT-PCR analysis
      showed that among the four members of the AP-2 gene family, AP-2alpha mRNA was
      the most abundant. AP-2alpha mRNA levels progressively declined during the
      differentiation induced by either insulin or TGF-beta treatment. Retroviral
      expression of AP-2alpha in ATDC5 cells prevented the formation of cartilage
      nodules, suppressed the proteoglycan production, and inhibited the expression of
      type II collagen, aggrecan, and type X collagen. Expression profile analysis of
      key transcription factors involved in chondrogenesis showed that overexpression
      of AP-2alpha maintained the expression of Sox9 but suppressed the expression of
      SoxS and Sox6. Taken together, we provide, for the first time, molecular and
      cellular evidence suggesting that AP-2alpha is a negative regulator of
      chondrocyte differentiation.

PMID- 14969395
TI  - Adipogenic differentiation of human adult stem cells from bone marrow stroma
      (MSCs).
AB  - We assayed gene expressions during adipogenesis of human MSCs. Microarray assays
      demonstrated time-dependent increases in expression of 67 genes, including 2
      genes for transcription factors that were not previously shown to be expressed
      during adipogenesis. INTRODUCTION Increased numbers of bone marrow adipocytes
      have been observed in patients with osteoporosis and aplastic anemia, but the
      pathological mechanisms remain unknown. Recently, microarray assays for mRNAs
      were used to follow adipogenic differentiation of the preadipocytic cell line,
      3T3-L1, but adipogenic differentiation has not been examined in primary cells
      from bone marrow. Here we defined the sequence of gene expression during the
      adipogenesis ex vivo of human cells from bone marrow referred to as either
      mesenchymal stem cells or marrow stromal cells (MSCs). MATERIALS AND METHODS:
      MSCs were plated at extremely low densities to generate single-cell derived
      colonies, and adipogenic differentiation of the colonies assayed by accumulation
      of fat vacuoles, time-lapse photomicroscopy, microarrays, and reverse
      transcriptase-polymerase chain reaction (RT-PCR) assays. RESULTS AND CONCLUSIONS
      About 30% of the colonies differentiated to adipocytes in 14 days and about 60%
      in 21 days. Cell proliferation was inhibited by approximately 50% in adipogenic
      medium. The differentiation occurred primarily at the center of the colonies, and
      a few adipocytes that formed near the periphery migrated toward the centers. RT
      PCR assays demonstrated that the differentiation was accompanied by increases in
      a series of genes previously shown to increase with adipogenic differentiation:
      peroxisome proliferator activated receptor gamma, CCAAT enhancer-binding protein
      alpha, acylCoA synthetase, lipoprotein lipase, and fatty acid binding protein 4.
      We also followed differentiation with microarray assays. Sixty-seven genes
      increased more than 10-fold at day 1 and 20-fold at day 7, 14, or 21. Many of the
      genes identified were previously shown to be expressed during adipocytic
      differentiation. However, others, such as zinc finger E-box binding protein and
      zinc finger protein 145, were not. This study should serve as a basis for future
      study to clarify the mechanisms of adipocyte differentiation of MSCs.

PMID- 14969396
TI  - Vitamin D receptor expression in human muscle tissue decreases with age.
AB  - Intracellular 1,25-dihydroxyvitamin D receptor (VDR) is expressed in human
      skeletal muscle tissue. However, it is unknown whether VDR expression in vivo is
      related to age or vitamin D status, or whether VDR expression differs between
      skeletal muscle groups. INTRODUCTION: We investigated these factors and their
      relation to 1,25-dihydroxyvitamin D receptor (VDR) expression in freshly removed
      human muscle tissue. MATERIALS AND METHODS: We investigated biopsy specimens of
      the gluteus medius taken at surgery from 20 female patients undergoing total hip
      arthroplasty (mean age, 71.6 +/- 14.5; 72% > 65 years) and biopsy specimens of
      the transversospinalis muscle taken at surgery from 12 female patients with
      spinal operations (mean age, 55.2 +/- 19.6; 28% > 65 years). The specimens were
      obtained by immunohistological staining of the VDR using a monoclonal rat
      antibody to the VDR (Clone no. 9A7). Quantitative VDR expression (number of VDR
      positive nuclei) was assessed by counting 500 nuclei per specimen and person.
      Serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were
      assessed at day of admission to surgery. RESULTS: All muscle biopsy specimens
      stained positive for VDR. In the univariate analyses, increased age was
      associated with decreased VDR expression (r = 0.5: p = 0.004), whereas there were
      no significant correlations between VDR expression and 25-hydroxyvitamin D or
      1,25-dihydroxyvitamin D levels. VDR expression did not differ between patients
      with hip and spinal surgery. In the multivariate analysis, older age was a
      significant predictor of decreased VDR expression after controlling biopsy
      location (gluteus medius or the transversospinalis muscle), and 25-hydroxyvitamin
      D levels (linear regression analysis: beta-estimate = -2.56; p = 0.047).
      CONCLUSIONS: Intranuclear immunostaining of the VDR was present in muscle biopsy
      specimens of all orthopedic patients. Older age was significantly associated with
      decreased VDR expression, independent of biopsy location and serum 25
      hydroxyvitamin D levels.

PMID- 14969397
TI  - A genome-screen of a large twin cohort reveals linkage for quantitative
      ultrasound of the calcaneus to 2q33-37 and 4q12-21.
AB  - A genome-wide screen was performed on a large cohort of dizygous twin pairs to
      identify regions of the genome that contain QTL for QUS of bone. Suggestive
      linkage of QUS parameters to 2q33-37 and 4q12-21 highlighted these regions as
      potentially important for studies of genes that regulate bone. INTRODUCTION: The
      genetics of osteoporotic fracture is only partly explained by bone mineral
      density (BMD). Quantitative ultrasound (QUS) of the calcaneus can also be used
      for independent clinical assessment of osteoporotic fracture risk. Two specific
      indices are derived from this assessment: broadband ultrasound attenuation (BUA)
      and velocity of sound (VOS). Both parameters provide information on fracture
      risk; however, BUA has been studied more extensively and may be favored because
      it is thought to have a stronger predictive value for osteoporotic fracture and
      incorporates aspects of trabecular structure and bone quality as well as BMD.
      Studies of QUS in twins have shown that both derived parameters are under
      substantial genetic control, independent of BMD. MATERIALS AND METHODS: To
      identify regions of the genome that contain quantitative trait loci (QTL) for QUS
      of bone, we performed a genome-wide screen on a large cohort of dizygous twin
      pairs. Unselected female dizygous twins from 1067 pedigrees from the St Thomas'
      UK Adult Twin Registry were genome scanned (737 highly polymorphic microsatellite
      markers). Multipoint linkage analyses provided maximum evidence of linkage for
      BUA (LOD 2.1-5.1) to 2q33-37. Linkage for VOS (LOD 2.2-3.4) was maximal at 4q12
      21. Potential evidence of linkage in the cohort indicated five other possible
      locations of QTL (LOD > 2.0) relevant to bone density or structure on chromosomes
      1, 2, 13, 14, and X. RESULTS AND CONCLUSIONS: This study has identified eight
      genomic locations with linkage of LOD > 2.0. This data should be of value in
      assisting researchers to localize genes that regulate bone mass and
      microstructure. These results should complement genome screens of BMD and bone
      structure and serve to enable further targeted positional candidate and
      positional cloning studies to advance our understanding of genetic control of
      bone quality and risk of fracture.

PMID- 14969398
TI  - Statins prevent bisphosphonate-induced gamma,delta-T-cell proliferation and
      activation in vitro.
AB  - The acute phase response is the major adverse effect of intravenously
      administered N-BPs. In this study we show that N-BPs cause gamma,delta-T-cell
      activation and proliferation in vitro by an indirect mechanism through inhibition
      of FPP synthase, an effect that can be overcome by inhibiting HMG-CoA reductase
      with a statin. These studies clarify the probable initial cause of the acute
      phase response to N-BP drugs and suggest a possible way of preventing this
      phenomenon. INTRODUCTION: The acute phase response is the major adverse effect of
      intravenously administered nitrogen-containing bisphosphonate drugs (N-BPs), used
      in the treatment of metabolic bone diseases. This effect has recently been
      attributed to their action as non-peptide antigens and direct stimulation of
      gamma,delta-T-cells. However, because N-BPs are potent inhibitors of farnesyl
      diphosphate (FPP) synthase, they could cause indirect activation of gamma,delta-T
      cells owing to the accumulation of intermediates upstream of FPP synthase in the
      mevalonate pathway, such as isopentenyl diphosphate/dimethylallyl diphosphate,
      which are known gamma,delta-T-cell agonists. MATERIALS AND METHODS: Peripheral
      blood mononuclear cells (PBMCs) were isolated from healthy volunteers and treated
      with N-BP, statin, or intermediates/inhibitors of the mevalonate pathway for 7
      days in the presence of interleukin (IL)-2. Flow cytometric analysis of the T
      cell-gated population was used to quantify the proportion of gamma,delta-T-cells
      in the CD3+ population. RESULTS AND CONCLUSIONS: The ability of N-BPs to
      stimulate proliferation of CD3+ gamma,delta-T-cells in human PBMC cultures
      matched the ability to inhibit FPP synthase. Gamma,delta-T-cell proliferation and
      activation (interferon gamma [IFNgamma] and TNFalpha release) was prevented by
      mevastatin or lovastatin, which inhibit HMG-CoA reductase upstream of FPP
      synthase and prevent the synthesis of isopentenyl diphosphate/dimethylallyl
      diphosphate. Desoxolovastatin, an analog of lovastatin incapable of inhibiting
      HMG-CoA reductase, did not overcome the stimulatory effect of N-BP. Furthermore,
      statins did not prevent the activation of gamma,delta-T-cells by a synthetic
      gamma,delta-T-cell agonist or by anti-CD3 antibody. Together, these observations
      show that N-BPs indirectly stimulate the proliferation and activation of
      gamma,delta-T-cells caused by inhibition of FPP synthase and intracellular
      accumulation of isopentenyl diphosphate/ dimethylallyl diphosphate in PBMCs.
      Because activation of gamma,delta-T-cells could be the initiating event in the
      acute phase response to bisphosphonate therapy, co-administration of a statin
      could be an effective approach to prevent this adverse effect.

PMID- 14969399
TI  - Water content measured by proton-deuteron exchange NMR predicts bone mineral
      density and mechanical properties.
AB  - NMR was used to measure matrix water content in normal and hypomineralized
      cortical bone. Water content showed an inverse relationship with mineral content,
      suggesting it could serve as a surrogate measure for the bone's degree of
      mineralization. INTRODUCTION: So far, true bone mineral density (DMB; degree of
      mineralization of bone) can not be measured nondestructively. MATERIALS AND
      METHODS: Here, a new technique combining 1H nuclear magnetic resonance (NMR)
      spectroscopy and deuterium isotope exchange was used to measure water content in
      cortical bone from two groups of rabbits: a control group and a group fed a low
      phosphorus (P) diet to induce hypomineralization of the bone matrix. RESULTS: NMR
      derived water content was higher in the P-depleted group and showed an inverse
      relationship with mineral content (measured gravimetrically and by 31p NMR).
      Hypomineralized bone was found to be weaker than normal bone as demonstrated by
      mechanical testing. More importantly, the data showed a strong inverse
      correlation between water content and bone mechanical properties, which indicates
      that water content could be predictive of the bone's mechanical competence.
      CONCLUSIONS: Water content could potentially serve as a surrogate measure for the
      bone's degree of mineralization, and this technique could be used to study other
      disorders of mineral homeostasis known to alter the mineralization state of the
      matrix. Although the method presented here is not suitable for in vivo
      measurements of bone water content, the authors have previously shown that 1H NMR
      images of bone can be acquired; thus, noninvasive quantification of bone water
      may be feasible.

PMID- 14969400
TI  - Dietary silicon intake is positively associated with bone mineral density in men
      and premenopausal women of the Framingham Offspring cohort.
AB  - The role of dietary silicon in bone health in humans is not known. In a cross
      sectional, population-based study (2847 participants), associations between
      dietary silicon intake and BMD were investigated. Dietary silicon correlated
      positively and significantly with BMD at all hip sites in men and premenopausal
      women, but not in postmenopausal women, suggesting that increased silicon intake
      is associated with increased cortical BMD in these populations. INTRODUCTION:
      Osteoporosis is a burgeoning health and economic issue. Agents that promote bone
      formation are widely sought. Animal and cellular data suggest that the
      orthosilicate anion (i.e., dietary silicon) is involved in bone formation. The
      intake of silicon (Si, approximately 30 mg/day) is among the highest for trace
      elements in humans, but its contribution to bone health is not known. MATERIALS
      AND METHODS: In a cross-sectional, population-based study, we examined the
      association between silicon intake and bone mineral density (BMD) in 1251 men and
      1596 pre- and postmenopausal women in the Framingham Offspring cohort (age, 30-87
      years) at four hip sites and lumbar spine, adjusting for all potential
      confounding factors known to influence BMD and nutrient intake. RESULTS: Silicon
      intake correlated positively with adjusted BMD at four hip sites in men and
      premenopausal women, but not in postmenopausal women. No significant association
      was observed at the lumbar spine in any group. Categorical analysis by Si intake,
      or energy-adjusted Si intake, supported these findings, and showed large
      differences in BMD (up to 10%) between the highest (> 40 mg Si/day) and lowest (<
      14 mg Si/day) quintiles of silicon intake. A significant association at the
      lumbar spine in men was also observed. Further analyses indicated that some of
      the effects seen for moderate consumption of alcoholic beverages on BMD might be
      attributed to Si intake. CONCLUSIONS: These findings suggest that higher dietary
      silicon intake in men and younger women may have salutary effects on skeletal
      health, especially cortical bone health, that has not been previously recognized.
      Confirmation of these results is being sought in a longitudinal study and by
      assessment of the influence of silicon intake on bone markers in this cohort.

PMID- 14969401
TI  - Reduced incidence of hip fracture in the Old Order Amish.
AB  - The incidence of hip fracture was estimated in a community of Old Order Amish and
      compared with available data from non-Amish whites. Hip fracture rates were 40%
      lower in the Amish, and the Amish also experienced higher BMD. INTRODUCTION:
      Understanding the patterns of fracture risk across populations could reveal
      insights about bone health and lead to the earlier detection and prevention of
      osteoporosis. Toward this aim, we compared hip fracture incidence and bone
      mineral density (BMD) between an Old Order Amish (OOA) community, characterized
      by a rural and relatively active lifestyle, and non-Amish U.S. whites. MATERIALS
      AND METHODS: All hospital admissions for hip fracture among OOA individuals in
      Lancaster County, PA, were identified between 1995 and 1998 from four area
      hospitals. Hip fracture incidence was calculated by cross-referencing an
      available Anabaptist genealogy database with communities located within these
      hospital service areas and compared with non-Amish whites obtained from National
      Hospital Discharge data. Additionally, BMD at the hip was compared between 287
      Amish subjects and non-Amish whites from the National Health and Nutrition
      Examination Survey III survey. RESULTS AND CONCLUSIONS: OOA experienced 42% fewer
      hip fractures than would be expected had they experienced the same rate of hip
      fracture as observed in non-Amish whites (p < 0.01) and a higher mean BMD that
      was significant in women (p < 0.05) but not men. Further evaluation of lifestyle
      and/or genetic differences between Amish and non-Amish populations may shed
      insights into etiologic factors influencing hip fracture risk.

PMID- 14969402
TI  - Evidence of sustained skeletal benefits from impact-loading exercise in young
      females: a 3-year longitudinal study.
AB  - The skeletal effects from intensive exercise throughout puberty are undefined.
      Forty-five female gymnasts and 52 controls were studied over 3 years, including a
      heredity aspect. The effects of size, maturity, exercise, and diet were
      identified using a multilevel regression model. Results demonstrated sustained
      skeletal benefits resulting from exercise throughout all stages of pubertal
      development. INTRODUCTION: Weight-bearing exercise is beneficial for peak bone
      mass development. However, whether skeletal benefits achieved with exercise are
      maintained if training remains intensive throughout the pubertal years is not
      entirely clear. The influence of familial resemblance for bone mass remains
      undefined in physically active versus inactive children. The aim of this study
      was to investigate the long-term influences of impact-loading exercise on bone
      quantity and quality in young females after controlling for growth, maturation,
      and hereditary factors. MATERIALS AND METHODS: At baseline, 45 gymnasts (G) and
      52 normally active controls (C) 8-17 years of age were recruited. Anthropometry,
      diet, physical activity, and quantitative ultrasound (QUS) were measured annually
      for 3 consecutive years. DXA scans of total body (TB) and lumbar spine (LS) bone
      mineral content (BMC) and density (BMD) were taken three times at 1-year
      intervals. A multilevel regression model was fitted, and the independent effects
      of body size, maturity, physical activity, and diet were identified over time. To
      assess heredity influences, 27 G mothers and 26 C mothers volunteered for cross
      sectional measurements of anthropometry, QUS, and BMC/BMD. RESULTS AND
      CONCLUSIONS: Gymnasts were smaller and lighter (as were their mothers) than
      controls, but they had significantly higher QUS and axial and appendicular BMC
      and BMD, with > 170 g more bone mineral in TB across puberty (after adjustment
      for maturity [years from peak height velocity], height, weight, energy, and
      protein intake). Gymnasts had up to 24-51% higher BMC and 13-28% higher BMD,
      depending on skeletal site. These results provide evidence of sustained skeletal
      benefits from impact-loading exercise, which are unlikely to result entirely from
      heredity, throughout pubertal years.

PMID- 14969403
TI  - Relationship between pretreatment bone resorption and vertebral fracture
      incidence in postmenopausal osteoporotic women treated with risedronate.
AB  - It is unclear whether the antifracture efficacy of bisphosphonates depends on
      pretreatment bone turnover. We analyzed the risedronate phase III clinical
      programs using the urinary excretion of deoxypyridinoline (uDPD) as an index of
      pretreatment bone resorption rates. Risedronate reduced incident vertebral
      fractures in women with postmenopausal osteoporosis independent from pretreatment
      bone resorption. INTRODUCTION: Earlier studies on postmenopausal osteoporosis
      have suggested that the therapeutic efficacy of antiresorptive therapies might be
      influenced by pretreatment bone turnover. Because all of these studies have used
      bone mineral density (BMD) as the primary endpoint, it remains unclear whether
      this association holds true for incident fractures. MATERIALS AND METHODS: This
      study aims to answer this question in a post hoc analysis of a subset of the
      risedronate phase III clinical programs, using the urinary excretion of
      deoxypyridinoline (uDPD) as an index of pretreatment bone resorption (PBR). A
      total of 1593 women with postmenopausal osteoporosis that had baseline uDPD
      values and paired spinal radiographs available were pooled, in similar
      proportions, from the risedronate multinational and North American VERT, and from
      the risedronate HIP trials. Patients from treatment and placebo groups were
      stratified by the uDPD premenopausal normative median. The four resulting groups
      were balanced for age, years since menopause, body mass index, baseline femoral
      neck BMD, and number of prevalent fractures, but baseline lumbar spine BMD was
      significantly higher in patients with low PBR rates. RESULTS: In all groups, the
      proportion of patients with new vertebral fractures was higher in patients with
      baseline uDPD levels above the normative median. The incidence of vertebral
      fracture was significantly lower in groups assigned to risedronate compared with
      placebo. This effect was independent of PBR: in patients with high PBR, the
      relative risk (RR) of vertebral fracture after 1 year of risedronate was 0.28 (p
      = 0.03 compared with controls, absolute risk reduction 7.1%). In patients with
      low PBR, the RR of fracture after 1 year was 0.33 (p < 0.001, absolute risk
      reduction 4%). After 3 years, the RR of fracture was 0.52 (p = 0.042, absolute
      risk reduction 8.3%) in patients with high PBR, and 0.54 (p = 0.002, absolute
      risk reduction 7.1%) in patients with low PBR. Results were similar after
      adjusting for age, baseline lumbar spine BMD, and prevalent fractures. The number
      needed to treat to avoid one vertebral fracture at 12 months was 15 in the group
      of patients with high PBR and 25 in patients with low PBR. Risedronate
      significantly increased lumbar spine BMD. During the first year of treatment,
      women with high PBR gained lumbar spine BMD at a faster rate than patients with
      low PBR. Treatment-by-PBR status interactions were not significantly different
      over time. CONCLUSION: The efficacy of risedronate to reduce incident vertebral
      fractures in women with postmenopausal osteoporosis is largely independent of
      pretreatment bone resorption rates.

PMID- 14969404
TI  - Relationship between changes in bone mineral density and fracture risk reduction
      with antiresorptive drugs: some issues with meta-analyses.
AB  - Published meta-analyses have investigated the relationship between changes in BMD
      and fracture risk reduction observed with antiresorptive agents, with
      inconsistent results. Many factors may affect the outcome of such analyses. Our
      work explores some of these factors and illustrates the need for caution in
      interpreting the results of meta-analyses. INTRODUCTION: The role of the increase
      in bone mineral density (BMD) in fracture risk reduction observed in osteoporotic
      patients treated with antiresorptive drugs is unclear. We examined the effects of
      study selection, the use of summary statistics or individual patient data (IPD)
      as the basis for the analyses, and the choice of BMD values used on the outcome
      of meta-analyses. MATERIALS AND METHODS: To evaluate the effects of study
      selection, we performed Poisson regression analyses using the results from a
      number of published studies. To evaluate the effects of using individual patient
      data instead of summary statistics, we simulated the IPD for vertebral fracture
      to match the summary statistics for published trials and compared these results
      with those based on meta-regression using summary statistics. We also evaluated
      the effect of varying the BMD increase with treatment (3-8%) used in predicting
      the fracture risk reductions in these simulations. RESULTS: The Poisson
      regression, which found a statistically significant relationship between
      nonvertebral fracture risk and spinal BMD when 18 trials of varying designs,
      duration, and sample size were included in the analysis (p = 0.02), was no longer
      significant when the analysis was based on the 7 large studies that were placebo
      controlled, at least 3 years in duration (at least 1000 patient-years). Meta
      analyses of simulated IPD from 12 trials of six antiresorptive agents gave
      accurate results regardless of the proportion of vertebral risk reduction assumed
      to be related to BMD change, whereas meta-regression based on summary statistics
      always produced an estimate around 50%. When the actual data from two risedronate
      studies were analyzed, the meta-regression based on summary statistics
      demonstrated a stronger correlation between BMD change and fracture risk
      reduction than the results based on the IPD analysis. In predicting the fracture
      risk reduction, the use of the average BMD gain (3%) observed in all studies in
      the calculations produced an overall fracture risk reduction very similar to the
      one observed clinically. In contrast, the use of a large BMD gain (8%) produced a
      substantially higher estimated fracture risk reduction and resulted in a high
      proportion of fracture risk reduction being attributed to BMD change.
      CONCLUSIONS: Many factors may influence the outcome of meta-analyses, and caution
      should be used in interpreting the results of such analyses when exploring the
      relationship between BMD changes and fracture risk reduction with antiresorptive
      therapy of osteoporosis.

PMID- 14969405
TI  - Nulliparity and osteoporotic fracture risk.

PMID- 14969406
TI  - An approach for cloning biosynthetic genes of 2-deoxystreptamine-containing
      aminocyclitol antibiotics: isolation of a biosynthetic gene cluster of tobramycin
      from Streptomyces tenebrarius.
AB  - Genes homologous to 2-deoxystreptamine (DOS) biosynthetic genes were isolated
      from aminoglycoside producers, Micromonospora and Streptomyces spp., using PCR
      primers based on the core sequences of 2-deoxy-scyllo-inosose (DOI) synthase and
      L-glutamine: scyllo-inosose aminotransferase (GIA). Identities of 40-45% were
      observed for DOI synthases, and 65-75% were observed for GIAs. The gene cluster
      of tobramycin biosynthesis was isolated from the genomic library of Streptomyces
      tenebrarius using DOI synthase as a probe. Sequencing of 33.9 kb revealed 24
      putative open reading frames including the tobramycin biosynthetic gene cluster
      (13.8 kb) and a transport protein. This cluster encodes proteins homologous to 2
      deoxystreptamine biosynthetic enzymes, glycosyltransferase and other
      aminocyclitols biosynthetic enzymes. Sequence analysis revealed the evolution of
      DOI synthases from 3-dehydroquinate (DHQ) synthases in actinomycetes. DOI
      synthases and GIA are therefore useful for cloning biosynthetic genes of DOS
      containing aminocyclitol antibiotics or for screening such metabolites producers.

PMID- 14969407
TI  - Identification of auto-antibodies in the sera of patients with rheumatoid
      arthritis.
AB  - Serological analysis of a recombinant cDNA expression library was carried out and
      a number of auto-antibodies were found that were highly prevalent in the sera of
      such patients.

PMID- 14969408
TI  - Cellulose production by Gluconacetobacter hansenii in a medium containing
      ethanol.
AB  - The addition of 1% (v/v) ethanol to the basal medium inhibited growth of
      Gluconacetobacter hansenii but decreased the numbers of non-cellulose producing
      cells. Cellulose production increased 1.7 times to approx. 2.5 g l(-1) and showed
      a pattern of mixed growth-associated production. Microbial cells produced rigid
      pellicle-type bacterial cellulose as the shell of a large lump of bacterial
      cellulose like a static culture. The inoculum cultivated for 3 d maintained
      cellulose production by the fifth batch.

PMID- 14969409
TI  - Monitoring the polysaccharide quality of Agaricus blazei in submerged culture by
      examining molecular weight distribution and TNF-alpha release capability of
      macrophage cell line RAW 264.7.
AB  - A method for monitoring the biological activity of broth polysaccharides of
      Agaricus blazei (AB-BP) in a submerged culture is described. The TNF-alpha
      releasing capability of AB-BP on the macrophage cell line, RAW 264.7, correlated
      with the molecular weight of AB-BP. The quality of polysaccharide in a submerged
      culture of Agaricus blazei was indirectly monitored by analyzing the distribution
      of its molecular weight within 1 h. The harvest time of the maximum
      polysaccharide production did not coincide with that of the maximum biological
      characteristics in the batch culture.

PMID- 14969410
TI  - Production of xylitol from Candida tropicalis by using an oxidation-reduction
      potential-stat controlled fermentation.
AB  - An on-line device, ORP (oxidation-reduction potential)-stat, was used to control
      glucose-feeding for enhancing xylitol conversion from D-xylose during an oxygen
      limited fermentation by Candida tropicalis. The fermentation was carried out in a
      5 l jar fermenter. After glucose in the medium was depleted, a switching to a
      limited aeration and feeding glucose controlled by ORP-stat was performed. The
      maximum xylitol yield was obtained under a condition at an ORP of -180 mV and at
      an aeration rate of 0.2 l min(-1).

PMID- 14969411
TI  - Analysis of spinal cord proteome in the rats with mechanical allodynia after the
      spinal nerve injury.
AB  - Proteome analysis was carried out to identify the proteins associated with
      neuropathic pain after peripheral nerve injury. Five proteins displayed different
      expression levels among three groups of rats. Among these proteins, creatine
      kinase B expression level was lower in the pain-positive rats compared to the
      sham or pain-negative rats. Therefore, a lower creatine kinase B expression level
      may be important in the development and maintenance of neuropathic pain.

PMID- 14969412
TI  - Methodology for using a universal primer to label amplified DNA segments for
      molecular analysis.
AB  - Detection of human DNA polymorphisms using high throughput methods often relies
      on generating a labeled DNA fraament which is generated by PCR using sequence
      specific primers with an end labeled tag to detect a variant. The disadvantage of
      the synthesis of an end-labeled, sequence-specific primer to assay each DNA
      variant lies in the costs and time consume. In this report, we have demonstrated
      a methodology that can generate labeled DNA fragments using a labeled universal
      primer instead of requiring sequence-specific primers for each DNA variant.

PMID- 14969413
TI  - Xylitol production by Candida tropicalis in a chemically defined medium.
AB  - A chemically defined medium that included urea (5 g l(-1)) as a nitrogen source
      and various vitamins was substituted for a complex medium containing yeast
      extract (10 g l(-1)) in the production of xylitol by Candida tropicalis. In a fed
      batch culture with the chemically defined medium, 237 g xylitol l(-1) was
      produced from 270 g xylose l(-1) after 120 h. The volumetric rate of xylitol
      production and the xylitol yield from xylose were 2 g l(-1) h(-1) and 89%,
      respectively. These values were about 5% lower and 4% higher, respectively, than
      those obtained using the complex medium. These results indicate that xylitol can
      be produced effectively in a chemically defined medium.

PMID- 14969414
TI  - Epifluorescence microscope methods for bacterial enumeration in a 4-chlorophenol
      degrading consortium.
AB  - Epifluorescence microscope methods, namely BacLight, direct epifluorescence
      filter technique and Rhodamine 123, consistently underestimated plate bacterial
      counts in a 4-chlorophenol degrading consortium. Cells capable of passing through
      0.2 microm filters, referred as 'ultramicrocells', were found. Although cell
      counts were higher when traditional methods were used, BacLight and direct
      epifluorescence filter technique were convenient techniques for the systematic
      monitoring of bacteria involved in biodegradation processes, as results were
      consistent and available within a short time.

PMID- 14969415
TI  - Extracts of Phellinus linteus grown on germinated brown rice suppress liver
      damage induced by carbon tetrachloride in rats.
AB  - Extracts of Phellinus linteus (EPB), grown on germinated brown rice, protected
      rats from liver injury induced by carbon tetrachloride (CCl4). Peroxidation
      products in the liver were decreased to 10% by EPB. Catalase and superoxide
      dismutase activities were significantly decreased to 55% and 39% by CCl4
      administration, but EPB blocked this effect, resulting in enzyme activities at
      control levels. Expression of cytochromeP450 2E1 (CYP2E1) protein was
      significantly decreased to 88% in CCl4-treated rats but remained at control
      levels when EPB was also administered. EPB did not affect the altered fatty acid
      composition induced by CCl4. The hepatoprotective effect of EPB may be mediated
      by EPB's prevention of CCl4-induced CYP2E1 degradation.

PMID- 14969416
TI  - Refolding and purification of Apo2l/TRAIL produced as inclusion bodies in high
      cell-density cultures of recombinant Escherichia coli.
AB  - As a new member of tumor necrosis factor (TNF) superfamily, TNF-related apoptosis
      inducing ligand (Apo2L/TRAIL) was produced mainly as inclusion bodies by
      recombinant Escherichia coli with a temperature-inducible expression system. High
      concentrations of both biomass (65 g dry cells l(-1)) and inactive TRAIL (4.8 g
      l(-1)) were obtained by applying a high-cell-density cultivation procedure. After
      the inclusion bodies were washed and solubilized. TRAIL refolded when at 1 mg ml(
      1) by a simple pulse dilution method with a 35% yield. Renatured TRAIL was
      purified to electrophoretic homogeneity by one-step immobilized metal affinity
      chromatography. The purified TRAIL showed strong cytotoxicity activity against
      human pancreatic 1990 tumor cells, with ED50 about 1.6 microg ml(-1).

PMID- 14969417
TI  - Scale-up of erythritol production by an osmophilic mutant of Candida magnoliae.
AB  - Erythritol production by an osmophilic mutant of Candida magnoliae was performed
      in fermentations of up 50 l to develop an optimized commercial process. By
      simultaneous feeding glucose and yeast extract, erythritol productivity of 1.2 g
      l(-1) h(-1) was reached giving 200 g erythritol l(-1) with a yield of 0.43 g g(
      1).

PMID- 14969418
TI  - Purification and biochemical properties of a galactooligosaccharide producing
      beta-galactosidase from Bullera singularis.
AB  - A beta-galactosidase, catalyzing lactose hydrolysis and galactooligosaccharide
      (GalOS) synthesis from lactose, was extracted from the yeast, Bullera singularis
      KCTC 7534. The crude enzyme had a high transgalactosylation activity resulting in
      the oligosaccharide conversion of over 34% using pure lactose and cheese whey
      permeate as substrates. The enzyme was purified by two chromatographic steps
      giving 96-fold purification with a yield of 16%. The molecular weight of the
      purified enzyme (specific activity of 56 U mg(-1)) was approx. 53 000 Da. The
      hydrolytic activity was the highest at pH 5 and 50 degrees C, and was stable to
      45 degrees C for 2 h. Enzyme activity was inhibited by 10 mM Ag3+ and 10 mM SDS.
      The Km for lactose hydrolysis was 0.58 M and the maximum reaction velocity
      (V(max)) was 4 mM min(-1). GalOS, including tri- and tetra-saccharides were
      produced with a conversion yield of 50%, corresponding to 90 g GalOS l(-1) from
      180 g lactose l(-1) by the purified enzyme.

PMID- 14969419
TI  - Epoxide hydrolase-catalyzed resolution of ethyl 3-phenylglycidate using whole
      cells of Pseudomonas sp.
AB  - A Pseudomonas sp. was isolated with enantioselective epoxide hydrolase activity
      to ethyl 3-phenylglycidate. Cells grown on sucrose and suspended in 10% (v/v)
      dimethyl formamide as co-solvent produced (2R,3S) ethyl 3-phenylglycidate with
      95% ee and 26% yield in 12 h from 0.2% (w/v) of the racemate.

PMID- 14969420
TI  - Prevention of osteoporosis in ovariectomized mice by electroporational gene
      transfer of parathyroid hormone.
AB  - Non-viral vector, pCMV-Pth, with full-length human parathyroid hormone (prepro
      hPTH) cDNA was constructed and delivered into the ovariectomized mouse quadriceps
      to explore the effects of electroporational gene transfer of PTH on the bone. The
      expression of hPTH in the transfected mice was detected by RT-PCR and
      radioimmunoassay. Mechanical testing and the analysis of bone mineral content
      demonstrated the improvement of bone properties. These results suggest that the
      electroporational gene taransfer of parathyroid hormone might be a promising
      method to prevent the bone loss in the postmenopausal women.

PMID- 14969421
TI  - The effects of activation and blockade of central P2X receptors on body
      temperature.
AB  - The aim of the present work was to identify the role of ATP acting on specific
      P2X receptors in the central mechanisms of thermoregulation. Immunohistochemical
      studies demonstrated that brainstem structures involved in controlling body
      temperature contained large number of nerve cells bearing P2X ATP receptors.
      Experiments on conscious rats involving intracerebroventricular administration of
      an ATP analog and P2X antagonists showed that both activation and blockade of
      central P2X receptors produced marked changes in body temperature. Analysis of
      the effects of these substances provided grounds for suggesting that ATP acting
      on P2X receptors fulfils an important function in the mechanisms of transmitting
      afferent information from peripheral thermal receptors to thermoregulatory
      centers in the brainstem with responsibility for heat loss, while in pyrogen
      induced fever ATP acting on these receptors may be involved in the activity of
      the endogenous antipyretic system.

PMID- 14969422
TI  - Selank and short peptides of the tuftsin family in the regulation of adaptive
      behavior in stress.
AB  - White laboratory male rats, inbred male C57BL/6 and Balb/c mice, and male Wistar
      rats, all previously divided on the basis of the type of emotional reactivity,
      were used to compare the effects of ten peptide compounds of the tuftsin family
      and Selank on the behavioral manifestations of emotional stress created by a
      conflict situation. Peptides were shown to have positive emotional effects and
      antistress actions. Individual physiologically significant effects were seen, due
      to the molecular structures of the study peptides and/or their degradation
      fragments. The results demonstrate the potential for the synthesis of peptide
      compounds with predictable directions of pharmacological actions and safe for
      wide use.

PMID- 14969423
TI  - Responses of the hypophyseal-adrenal system to stress and immune stimuli in gray
      rats selected for behavior.
AB  - The characteristics of the responses of the hypothalamo-hypophyseal-adrenal
      system to restriction stress and administration of lipopolysaccharide and
      interleukin-2 were studied in gray rats selected for the maintenance and absence
      of aggressive behavior in relation to humans. These experiments demonstrated
      decreased levels of corticosterone and ACTH in the plasma of tame rats in
      restriction stress and after administration of lipopolysaccharide as compared
      with non-tame rats. After administration of interleukin-2, the corticosterone
      level was identical in both groups of animals, though it reached the basal level
      in tame rats more quickly than in rats selected for maintaining aggressive
      behavior. Thus, selection of gray rats for tame behavior induces not only
      decreases in the responses of the hypophyseal-adrenal system to restriction
      stress, but also changes its response to immune stimuli and also, perhaps, its
      interaction with the immune system.

PMID- 14969424
TI  - Mechanisms of generation of mismatch negativity and their role in the recognition
      of brief auditory stimuli.
AB  - The endogenous components of auditory evoked potentials were studied in the human
      brain, arising in conditions of voluntary and involuntary attention. Variation of
      the duration of acoustic stimuli led to a situation in which the generation of
      mismatch negativity was blocked. The recognition of acoustic stimuli was compared
      in conditions in which passive perception of the deviant signal in some cases
      evoked mismatch negativity and in others did not. This demonstrated the
      following: 1) stimuli not evoking mismatch negativity in the classical "oddball"
      paradigm can be recognized efficiently; 2) recognition of stimuli evoking
      mismatch negativity (in conditions of passive perception) occurs with a
      significantly shorter response time. The difference in the present experiments
      was 49-51 msec. There was also an increase in the proportion of correct responses
      to the deviant stimulus (to 92%). Thus, if the experimental conditions allow the
      mechanism generating mismatch negativity to trigger, then the response time to
      the actively perceived stimulus decreases. These results are evidence that the
      mechanisms of involuntary attention contribute to the active perception of
      acoustic stimuli.

PMID- 14969425
TI  - Involvement of GABA(B) receptors in presynaptic inhibition of fibers of the
      descending projections of the spinal cord in the frog Rana ridibunda.
AB  - Isolated spinal cord preparations from Rana ridibunda frogs were used for studies
      of the effects of the GABA(B) receptor agonists (-)-baclofen (50 and 100 microM)
      and GABA (4-8 mM) and the specific GABA(B) receptor antagonist 2-hydroxysaclofen
      (100 microM) on the transmission of signals from fibers of the ventral columns
      monosynaptically connected with motoneurons in segments 9 and 10. These
      experiments showed that (-)-baclofen (50 and 100 microM) produced significant and
      dose-dependent suppression of excitatory postsynaptic potentials (EPSP) in
      motoneurons and ventral root potentials evoked by stimulation of fibers of the
      ipsi- and contralateral ventral columns. The inhibitory effect of (-)-baclofen
      (100 microM) on descending EPSP was 35-50% blocked by the GABA(B) receptor
      antagonist 2-hydroxysaclofen (0.2 mM). The inhibitory effect of GABA (4-8 mM) on
      descending EPSP was 60% blocked by the GABA(A) receptor antagonist picrotoxin
      (0.05 mM). (-)-Baclofen (50 microM) and GABA (4 and 6 mM) were found to have
      inhibitory effects on ventral root potentials evoked by stimulation of the ipsi-
      and contralateral ventral columns. The data obtained here, as well as data
      obtained by pharmacological analysis and conditioning by stimulation of the ipsi-
      and contralateral ventral columns, are regarded as a significant argument
      supporting the existence of GABA(B) receptor-mediated presynaptic inhibition of
      descending fibers connected monosynaptically to spinal cord motoneurons in the
      frog Rana ridibunda.

PMID- 14969426
TI  - Brain blood flow modulates the neurotoxic action of hyperbaric oxygen via
      neuronal and endothelial nitric oxide.
AB  - Studies on conscious rats with inhibition of NO synthase were used to assess the
      dynamics of brain blood flow and EEG traces during hyperbaric oxygenation at 4 or
      5 atm. Oxygen at a pressure of 4 atm induced cerebral vasoconstriction in intact
      animals and decreased blood flow by 11-18% (p < 0.05) during 60-min exposure to
      hyperbaric oxygenation. Paroxysmal EEG activity and oxygen convulsions did not
      occur in rats at 4 atm of O2. At 5 atm, convulsive activity appeared on the EEG
      at 41 +/- 1.9 min, and blood flow decreased significantly during the first 20
      min; blood flow increased by 23 +/- 9%, as compared with controls, (p < 0.01)
      before the appearance of convulsions on the EEG. Prior inhibition of NO synthase
      I (NOS I) and NO synthase III (NOS III) with N(omega)-nitro-L-arginine methyl
      ester (L-NAME, 30 mg/kg) or inhibition only of NOS I with 7-nitroindazole (7-NI,
      50 mg/kg) prevented the development of hyperoxic hyperemia and paroxysmal spikes
      on the EEG during hyperbaric oxygenation at 5 atm. These results show that
      hyperbaric oxygen induces changes in cerebral blood flow which modulate its
      neurotoxic action via nitric oxide synthesized both in neurons and in cerebral
      vessels.

PMID- 14969427
TI  - Lipid peroxidation in the striatum of rats during stress after administration of
      cortisol.
AB  - Lipid peroxidation processes were studied in the striatum during stress in
      conditions of prior administration of cortisol. Three doses of cortisol (25
      mg/kg, daily) had no significant effect on the levels of lipid peroxidation
      products six days after injections ended. However, lipid peroxidation responses
      to stress during this period in animals given cortisol were significantly
      stronger than in controls (there were decreases in the intermediate products of
      lipid peroxidation and increases in the quantities of Schiff bases). Thus,
      administration of hormone leads to long-term changes in one of the most important
      regulatory systems of the body--lipid peroxidation--and has sensitizing effects
      on changes in the levels of stress-induced lipid peroxidation products.

PMID- 14969428
TI  - The effects of epiphyseal peptides on the release of immunoglobulins in Peyer's
      patches in rats in vitro.
AB  - The effects of epiphyseal peptides (1 microg/ml) on the release of
      immunoglobulins into the incubation medium by isolated Peyer's patches from non
      immunized mice and mice immunized orally against ovalbumin were studied during 40
      min incubations. The possibility that epiphyseal peptides act on adrenoreceptors
      of cells in secondary lymphoid organs in the small intestine was assessed using
      alpha- and beta-adrenoreceptor blockers, i.e., phentolamine HCl (0.02 mg/ml) and
      anaprilin (0.06 mg/ml) respectively. Basal levels of secretory activity in
      control Peyer's patches from immunized rats were 2.4 times (p < 0.01) greater
      than for the lymphoid organs of non-immunized animals. The effects of epiphyseal
      peptides on the secretory activity of antibody-forming cells depended on the
      functional state of Peyer's patches. Application of epiphyseal peptides led to a
      35% increase (p < 0.05) in the release of immunoglobulins from Peyer's patches in
      non-immunized rats and a 25% decrease (p < 0.05) in the release of antibody into
      the incubation medium from the lymphoid organs of immunized animals. These data
      lead to the suggestion that the activatory effect of epiphyseal peptides on
      antibody-forming cells in Peyer's patches from non-immunized animals is
      associated with alpha-adrenoceptors, while their inhibitory action on
      immunoglobulin release by the small intestine lymphoid organs from immunized
      animals is not mediated via adrenoceptors.

PMID- 14969429
TI  - Anxiety levels and neurosteroid synthesis in the brains of prenatally stressed
      male rats.
AB  - This report presents studies of the effects of immobilization stress applied to
      pregnant female rats during the last third of pregnancy on anxiety levels and
      neurosteroid synthesis in brain structures of adult offspring. Neurosteroid
      synthesis was assessed in terms of changes in the activity of 5alpha-reductase,
      the enzyme which converts progesterone into active metabolites. Prenatal stress
      results in a significant decrease in the level of anxiety and an increase in
      movement activity among adult males. Stressed rats showed increases in
      progesterone-5alpha-reductase activity in the hypothalamus, hippocampus, and
      frontal cortex. These results provide evidence that changes in the behavior of
      adult male rats due to stress in the prenatal period of development may be due to
      the formation of active progesterone metabolites in the brain.

PMID- 14969430
TI  - Mechanisms of the influences of the central administration of substance P on
      ethanol consumption in chronically alcoholic rats.
AB  - The effects of central administration of substance P (SP) on alcohol consumption
      and dopamine metabolism in the projections of the mesocorticolimbic and
      nigrostriatal systems of the brain were studied in chronically alcoholic rats.
      Rats received 15% ethanol solution for 6 months without choice. Intraventricular
      administration of SP (1 microg/rat) decreased consumption of 10% ethanol solution
      by 41% compared with controls in an alcohol free choice test lasting one day.
      After chronic alcoholism, there was a decrease in the ratio of
      dihydroxyphenylacetic acid (DOPA) and homovanillic acid (HVA) to dopamine in the
      nucleus accumbens and striatum in rats subjected to alcoholism, as compared with
      intact controls. Chronically alcoholic rats treated with SP showed increases in
      DOPA, HVA, and the DOPA:dopamine and HVA:dopamine ratios in the nucleus accumbens
      as compared with animals given physiological saline, by 17%, 23%, 9% and 19%
      respectively. The only increases in the striatum were in the absolute levels of
      DOPA and HVA, by 28% and 29%, while the ratios of these metabolites to dopamine
      remained unchanged. Thus, central administration of SP decreased the voluntary
      consumption of ethanol in the ethanol free choice test and enhanced dopamine
      metabolism in structures of the mesolimbic and nigrostriatal systems in
      chronically alcoholic rats.

PMID- 14969431
TI  - Comparative characteristics of respiratory pattern responses to microinjection of
      kainic acid into different parts of the nucleus ambiguus.
AB  - Experiments on anesthetized rats were performed using local chemical exclusion of
      neurons with kainic acid to study the relative roles of the rostral,
      intermediate, and caudal parts of the nucleus ambiguus in the mechanisms
      controlling respiration. The characteristics of the respiratory rhythm and
      pattern responses to chemical exclusion of different parts of this nucleus were
      observed. In particular, sequential exclusion of the left and right rostral parts
      of the nucleus ambiguus reproducibly induced significant decreases in the
      respiration rate and respiratory volume in the first minutes; in 83% of
      experiments, there was also irreversible respiratory arrest. Exclusion of
      symmetrical intermediate parts of the nucleus ambiguus was followed by bradypnea
      and decreases in pulmonary ventilation, the greatest respiratory effects being
      noted only after injection of kainic acid into the second symmetrical area,
      irreversible respiratory arrest being seen in 50% of cases. Exclusion of
      symmetrical caudal areas of the nucleus ambiguus resulted only in small decreases
      in respiratory frequency without significant changes in respiratory volume and
      gave rise to the smallest incidence of respiratory arrest, i.e., 33%.

PMID- 14969432
TI  - Activity of neurons in the pedunculopontine nucleus during a food-related operant
      conditioned reflex.
AB  - The activity of 91 neurons in the compact and diffuse zones of the
      pedunculopontine nucleus of freely mobile rabbits was studied during performance
      of a food-related operant conditioned reflex. A total of 37.4% of the neurons
      recorded showed reactivity to the conditioned stimulus, which is evidence that
      the pedunculopontine nucleus is involved in operant learning. A significant
      predominance of excitatory responses to the conditioned stimulus and to food
      reinforcement was demonstrated. The main patterns of cell responses were
      identified, these reflecting the nature of the effect of the conditioned stimulus
      on neuron activity, the structure of the behavioral act, and the properties of
      the reinforcement, and demonstrating a relationship between the pedunculopontine
      nucleus and the processes of attention, motor learning, and reinforcement.
      Differences were seen in the associative reactive properties of the compact and
      diffuse zones of the pedunculopontine nucleus to the conditioned stimulus and
      reinforcement, which is evidence for the functional diversity of this formation
      and suggests a leading role for the cholinergic compact zone in food-related
      operant learning and reinforcement, the diffuse zone having a leading role in
      food-related classical conditioned-reflex learning.

PMID- 14969433
TI  - Regulation of post-tetanic increases in the cholinosensitivity of neurons in the
      common snail by the Na,K pump: the role of Na/Ca exchange and calcium
      mobilization.

PMID- 14969434
TI  - Impairments in premorbid knowledge recall in patients with hemispheric and
      intraventricular brain damage.
AB  - A total of 104 patients with hemispheric arteriovenous malformations (AVM; in the
      frontal, parietal, and temporal lobes), along with 21 patients with
      craniopharyngiomas and 21 patients with aresorptive hydrocephalus, were studied.
      Impairments of the recall of knowledge acquired before disease onset were found
      in 12 patients with hemispheric AVM. All had suffered severe intraventricular
      hemorrhage. Similar memory defects were noted in three patients with
      craniopharyngiomas and 12 with hydrocephalus. These patients had lesions of the
      mediobasal (periventricular) parts of the brain (frontal and parietal lobes),
      predominantly of the right hemisphere, as well as the diencephalic regions. The
      syndrome of selective retrograde amnesia in lesions of these structures was
      characterized by impairment of the recall of dates and, less frequently, details
      of event content and autobiography. It is emphasized that processes of recall of
      the sequence and selectivity of traces during actualization of "old" knowledge
      played the greater role in the mechanism of development of these impairments. The
      possible roles of the right and left hemispheres, as well as the diencephalic
      area, in the information encoding and decoding are discussed.

PMID- 14969435
TI  - Application of a sediment quality index to the lower Laurentian Great Lakes.
AB  - A sediment quality index (SQI) was developed using an equation incorporating
      three elements; scope--the % of variables that did not meet guidelines; area
      frequency--the % of failed tests divided by the total number of tests in a group
      of sites; and amplitude - the magnitude by which failed variables exceeded
      guidelines. The SQI calculation produces a numerical score with a maximum value
      of 100 representing the highest sediment quality. A modified SQI was also
      developed using only the scope and amplitude elements, which computed a score per
      site with no grouping. The SQI was applied to assessment of sediment quality in
      Lakes Erie and Ontario using Canadian Federal and Ontario Provincial guidelines
      for 34 compounds, Spatial trends in sediment quality in both lakes reflected
      overall trends for most individual contaminant classes, including mercury and
      polychlorinated biphenyls. In Lake Erie, there was a trend toward lower SQI
      values from the eastern basin to the western basin, and from the northern area to
      the southern area of the central basin. Sediment quality in the eastern basin and
      the northern area of the central basin was classified as excellent (>95);
      sediments in other areas of Lake Erie ranged from fair to good. In Lake Ontario,
      the poorest sediment quality was associated with the three major depositional
      basins; sediment quality among the three basins was quite consistent. The SQI
      values based on all three elements (scope, frequency and amplitude) for the
      Niagara basin. Mississauga Basin and Rochester Basin were 67 (fair), 65 (fair)
      and 70 (fair), respectively. Comparison of SQI values for all lower lake basins
      showed generally poorer sediment quality in Lake Ontario, compared to Lake Erie.

PMID- 14969436
TI  - Auditing the accuracy of a volunteer-based surveillance program for an aquatic
      invader Bythotrephes.
AB  - We tested the sampling methods of a volunteer-based monitoring program designed
      to detect the non-indigenous spiny water flea, Bythotrephes longimanus, and found
      that the program could detect the majority of Bythotrephes invasions. Volunteers
      take two vertical hauls with a 30 cm diameter net at each of three pelagic
      stations. To determine if the volunteers were using a large enough net at their
      three stations, we performed a 17-lake comparison of the volunteer's net with a
      75 cm diameter, research-grade net. We found no difference in the number of
      stations at which Bythotrephes was detected (paired t-test, p = 0.155) with the
      two nets, because Bythotrephes densities were above the detection limits for both
      nets. To determine if three stations were sufficient to detect the invader with
      the volunteer's net, we deployed it at 30 stations in two lakes with average
      (Harp Lake, 4.17 Bythotrephes m(-3)) vs. low Bythotrephes densities (Sugar Lake,
      0.92 m(-3)). In Harp Lake, repeated randomized sampling of the 30 sets of data
      indicated that only three stations were needed for 100% capture success. In Sugar
      Lake, seven stations were needed for 100% capture success, but three stations,
      the current program design, failed to detect the invasion only 14% of the time.

PMID- 14969437
TI  - A provisional fish index of biotic integrity for assessing Ouachita Mountains
      streams in Arkansas, U.S.A.
AB  - Multimetric indices are often used to monitor aquatic-resource conditions. We
      used existing fish-collection data from streams to develop an Index of Biotic
      Integrity (IBI), which is a multimetric index, for the Ouachita Mountains
      ecoregion in Arkansas, U.S.A. Each fish-collection site was categorized as
      reference or non-reference. We examined 62 candidate IBI metrics, and selected 12
      non-redundant metrics that differentiated best between reference and non
      reference sites. The selected metrics were: Percent (of individuals) as Black
      Bass; Percent as Benthic Feeders; Percent as Centrarchids; Percent as Cyprinids;
      Percent as Ictalurids; Percent as Mineral, Site-Prep Spawners; Percent as
      Mineral, Site-Prep, Parental-Care Spawners; Percent as Simple, Mineral Substrate
      Spawners; Percent as Miscellaneous, Site-Prep, Parental-Care Spawners; Total
      Number of Centrarchid Species; Total Number of Arkansas Department of
      Environmental Quality (ADEQ) Ouachita Mountains Indicator Species; and Total
      Number of ADEQ Ouachita Mountains Key Species. We standardized each metric to
      score from 0 to 10 by using linear equations and threshold limits. Some selected
      IBI metrics had their scoring criteria adjusted to account for watershed size
      (i.e., stream size). We standardized the IBI to score from 0 to 100. In addition,
      we determined that our Percent as Black Bass and Percent as Benthic Feeders
      metrics contributed most to IBI scores in reference conditions, but their
      contributions decreased with decreasing stream conditions. Reproductive metrics
      contributed most in degraded stream conditions. Furthermore, we identified
      relations between IBI metrics and water-quality and land-use variables; some
      relations were counterintuitive. Unexpected relations may be random observations
      explained by limited ranges of land-use and water-quality variables. When select
      water-quality and land-use variables were included in a principal component
      analysis, a composite Land Use Intensity variable explained most of the model
      variance. Although the IBI has not been independently validated, the PCA, as well
      as other superficial analyses, indicated that the IBI should be able to
      differentiate stream conditions.

PMID- 14969438
TI  - Integrative evaluation of the ecological quality of metalliferous streams
      (Chalkidiki, Macedonia, Hellas).
AB  - The present study reports on a year-long (November 1997-November 1998) study of
      water quality in streams of the Olympias and Skouries areas of Chalkidiki
      (Hellas), subject to past and present mining activities. Benthic
      macroinvertebrates were collected from 18 sampling sites at five sampling
      intervals, while several physicochemical parameters of the water (D.O., pH,
      temperature, nutrients etc.) were also measured. Five European biotic indices and
      scores and two multivariate statistical methods (CANOCO, FUZZY) were applied to
      the macroinvertebrate data. The concentration of various trace metals in the
      water, sediment, fish and crustaceans were also measured. Most sampling stations
      exhibited a highly diverse macroinvertebrate fauna during the whole year.
      However, a slight amelioration of water quality was observed during the high-flow
      period (winter and early spring), regarding diversity of several invertebrate
      groups, especially pollution-sensitive families, which decreased. The European
      biotic indices and scores proved to be relatively ineffective in describing water
      quality and it is suggested that an Hellenic biotic indice or score should be
      created. The bioaccumulation studies indicated variable effects of trace metals
      and organic load on macroinvertebrates according to the degree of load.

PMID- 14969439
TI  - Emissions of N2O and CH4 during the composting of liquid swine manure.
AB  - Composted organic wastes have been shown to reduce emissions of N2O and CH4, but
      little is known about the release of these gases during the composting process.
      This research examined the emissions of N2O and CH4 during the composting of
      liquid swine manure and wheat straw at two operations, one with forced aeration
      and the other without. The lack of aeration increased CH4 emissions to 24 times
      that of composting with aeration, but had no significant effect on N2O
      production. When total N2O and CH4 emissions from composting were compared with
      liquid swine manure emissions, aerated composting was found to reduce emissions
      to as low as 30% of those from liquid manure storage, while non-aerated
      composting elevated emissions up to an estimated 330% of liquid manure storage.

PMID- 14969440
TI  - Sediment contamination, by habitat, in the Tampa Bay estuarine system (1993
      1999): PAHs, pesticides and PCBs.
AB  - More than 760 Tampa Bay (Florida, U.S.A.) sediment samples have been analyzed for
      organic contaminants (PAHs, organochlorine pesticides, and PCBs) since 1993. Data
      were analyzed to assess status by habitat (defined by overlapping salinity zones
      and sediment type). The habitats most degraded by PAHs and pesticides were
      generally located in lower salinity, fine-grained sediment habitats, which are
      typically confined to the Hillsborough River. PCB contamination was more common
      in mesohaline waters of the Palm and Hillsborough rivers. Higher salinity
      portions of the bay, where medium to coarse sand-sized sediments predominate,
      showed little evidence of contamination by PAHs, PCBs and pesticides other than
      lindane.

PMID- 14969441
TI  - Optimal expansion of water quality monitoring network by fuzzy optimization
      approach.
AB  - River reaches are frequently classified with respect to various mode of water
      utilization depending on the quantity and quality of water resources available at
      different location. Monitoring of water quality in a river system must collect
      both temporal and spatial information for comparison with respect to the
      preferred situation of a water body based on different scenarios. Designing a
      technically sound monitoring network, however, needs to identify a suite of
      significant planning objectives and consider a series of inherent limitations
      simultaneously. It would rely on applying an advanced systems analysis technique
      via an integrated simulation-optimization approach to meet the ultimate goal.
      This article presents an optimal expansion strategy of water quality monitoring
      stations for fulfilling a long-term monitoring mission under an uncertain
      environment. The planning objectives considered in this analysis are to increase
      the protection degree in the proximity of the river system with higher population
      density, to enhance the detection capability for lower compliance areas, to
      promote the detection sensitivity by better deployment and installation of
      monitoring stations, to reflect the levels of utilization potential of water body
      at different locations, and to monitor the essential water quality in the upper
      stream areas of all water intakes. The constraint set contains the limitations of
      budget, equity implication, and the detection sensitivity in the water
      environment. A fuzzy multi-objective evaluation framework that reflects the
      uncertainty embedded in decision making is designed for postulating and analyzing
      the underlying principles of optimal expansion strategy of monitoring network.
      The case study being organized in South Taiwan demonstrates a set of more robust
      and flexible expansion alternatives in terms of spatial priority. Such an
      approach uniquely indicates the preference order of each candidate site to be
      expanded step-wise whenever the budget limitation is sensitive in the government
      agencies.

PMID- 14969442
TI  - Leaching characteristics of fly ash from thermal power plants of Soma and
      Tuncbilek, Turkey.
AB  - Use of lignite in power generation has led to increasing environmental problems
      associated not only with gaseous emissions but also with the disposal of ash
      residues. In particular, use of low quality coal with high ash content results in
      huge quantities of fly ash to be disposed of. The main problem related to fly ash
      disposal is the heavy metal content of the residue. In this regard, experimental
      results of numerous studies indicate that toxic trace metals may leach when fly
      ash contacts water. In this study, fly ash samples obtained from thermal power
      plants, namely Soma and Tuncbilek, located at the west part of Turkey, were
      subjected to toxicity tests such as European Committee for standardization (CEN)
      and toxicity characteristic leaching (TCLP) procedures of the U.S. Environmental
      Protection Agency (U.S. EPA). The geochemical composition of the tested ash
      samples from the power plant show variations depending on the coal burned in the
      plants. Furthermore, the CEN and TCLP extraction results showed variations such
      that the ash samples were classified as 'toxic waste' based on TCLP result
      whereas they were classified as 'non-toxic' wastes based on CEN results,
      indicating test results are pH dependent.

PMID- 14969443
TI  - Drainage effects on stream nitrate-N and hydrology in south-central Minnesota
      (USA).
AB  - Excessive nitrate-N in south-central Minnesota ditches and streams is related to
      land-use change, and may be contributing to the development of the zone of
      hypoxia in the Gulf of Mexico. Intensive land-use (agricultural management) has
      progressively increased as subsurface drainage has improved crop productivity
      over the past 25 years. We have examined water at varying scales for delta18O
      and, nitrate-N concentrations. Additionally, analysis of annual peak flows, and
      channel geomorphic features provided a measure of hydrologic change. Laboratory
      and field results indicate that agricultural drainage has influenced riverine
      source waters, concentrations of nitrate-N, channel dimensions and hydrology in
      the Blue Earth River (BER) Basin. At the mouth of the BER shallow ground water
      comprises the largest source water component. The highest nitrate-N
      concentrations in the BER and tributaries typically occurred in May and June and
      ranged from 7-34 mg L(-1). Peak flows for the 1.01-2-yr recurrence intervals
      increased by 20-to-206% over the past 25 years. Geomorphic data suggest that
      small channels (ditches) were entrenched by design, whereas, natural that are
      disconnected from an accessible riparian corridor. Frequent access to a
      functioning riparian zone is important for denitrification.

PMID- 14969444
TI  - Tobacco plants detect a decrease of environmental genotoxicity in Toulouse
      (France).
AB  - Tobacco plants, heterozygous for two independent loci involved in the chlorophyll
      parenchyma differentiation, allow the genotoxic effects of the atmosphere of the
      industrial estate South of Toulouse to be estimated. Somatic spots of green
      cellular colonies on yellow-green background, were counted to calculate the
      cellular rates of reversion. Two experiments were carried out in 1981, and in
      1997. A general decrease of genotoxic effects was observed. These observations
      were interpreted as being due to a general decrease of the air pollution
      evaluated by the development of the concentrations of three toxic gases before
      and after the implementation of cleanup devices. The results obtained demonstrate
      the efficiency of this bio-indicator, which is easy to use and capable of
      integrating, in situ, genotoxic variations throughout the duration of plants'
      growth.

PMID- 14969445
TI  - Sub-surface investigations on deep saline groundwater of Charnockite rock
      formation, Kalpakkam, India.
AB  - Investigations on geohydrological aspects of coastal aquifer are important in
      order to understand the mechanism of ground water salinisation. The present study
      describes the salinity variations of ground water in deep boreholes drilled in
      Charnockite rock formation of Kalpakkam, on the eastern coast of India. Water
      samples collected up to 600m depth were analyzed for salinity variation. It is
      noticed that in one of the boreholes, (borehole K1), the salinity level is found
      to be 74 parts per thousand (ppt) at 400 m depth. Influence of surface saline
      water bodies viz., sea (26-28.5 ppt), backwaters (27-30 pt) and Buckingham canal
      (27-32 ppt) as the possible sources of recharge of fresh waters through joint and
      fracture system of the rock are discussed in this paper. Studies would assist in
      understanding the geohydrological characteristics of deep geological formation.

PMID- 14969446
TI  - Ethnobotanical study of fuelwood and timber wood consumption and replenishment in
      Ogbomoso, Oyo State, Nigeria.
AB  - A survey of both urban and rural communities in five Local Government Areas (LGA)
      of Oyo State in Nigeria showed that 76% of households depend on fuelwood for
      cooking. The total annual wood consumption for fuelling by bread bakers, food
      sellers and in domestic cooking was 5984 metric tons for the region. The sawmills
      in the study area also convert 79 889 metric tons of wood yearly into boards of
      different grades. Total wood consumption outstrips the quantity of wood extracted
      from the forests. The balance of over 60 000 metric tons of wood is sourced from
      neighbouring forest locations. The quantity of wood harvested for various
      purposes did not show a significant difference (p < 0.05) among the five LGAs.
      However, a significant difference at p > 0.05 existed in the quantity of wood
      actually consumed in the various LGAs. Moreover. the number of trees cut down
      outstrips the number of trees planted with a significant difference (p > 0.05)
      between the mean quantity of wood removed from the forests and the mean quantity
      replaced by reforestation. The practice in the study area was that of 'cut-eight
      plant-one' which is at variance to the much publicized operation 'cut-one-plant
      one'. The study concludes that residents of Ogbomoso in Nigeria have not shown
      positive disposition to tree planting. It therefore suggests scientific tree
      conservation strategies aimed at improved burning of fuel wood and maximized use
      of timber products as complementary efforts to enforced tree planting for
      conservation of our forests.

PMID- 14969447
TI  - TPH-contaminated Mexican refinery soil: health risk assessment and the first year
      of changes.
AB  - The soil of a coastal Mexican refinery is quite contaminated, especially by
      hydrocarbons, with detected concentrations up to 130000 mg kg(-1) as TPHs (total
      petroleum hydrocarbons). The main sources of contamination are pipelines, valves,
      and old storage tanks, besides the land disposal of untreated hydrocarbon
      sediments derived from the cleaning of storage tanks. A health risk assessment
      (HRA) was carried out in order to measure the risk hazard indexes and clean-up
      standards for the refinery soil. HRA suggested the following actions to be taken:
      benzene concentrations must be reduced in eight of the 16 studied refinery zones
      to 0.0074-0.0078 mg kg(-1). Also, vanadium concentration must be reduced in two
      zones up to a concentration of 100 mg kg(-1). In only one of all of the studied
      zones, benzo(a)pyrene concentration must be reduced to 0.1 mg kg(-1). After 1 yr,
      TPHs showed a diminution of about 52%. Even though TPHs concentrations were
      variable, during 1999 the average concentrations were as much as 15.5 times the
      goal concentration. For year 2000, TPHs concentrations were only 7.4-fold the
      proposed value. For the 1999-2000 period, PAHs (polycyclic aromatic hydrocarbons)
      concentrations decreased by 82%. Some PAHs with 2, 3, 4, and 5 aromatic rings
      were removed up to 100% values.

PMID- 14969448
TI  - A preliminary assessment of Montreal process indicators of forest fragmentation
      for the United States.
AB  - As part of the U.S. 2003 National Report on Sustainable Forests, four metrics of
      forest fragmentation--patch size, edge amount, inter-patch distance, and patch
      contrast--were measured within 137744 non-overlapping 5625 ha analysis units on
      land-cover maps derived from satellite imagery for the 48 conterminous States.
      The perimeter of a typical forest patch is about 100 m from the perimeter of its
      nearest neighbor, except when there is not much forest, in which case that
      distance is 200 to 300 m. A typical analysis unit has from 10 to 40% as much
      forest edge as it could possibly have, given the amount of forest present. Most
      analysis units contain a large number of patches that are less than one hectare
      in size, and about 10% contain one or more 2000 to 5000 ha patches. Forest often
      defines the background landscape, and patch contrast is generally either very
      high or very low in eastern regions and intermediate in western regions. Many
      research needs were identified by this experimental analysis of available data
      and metrics.

PMID- 14969449
TI  - Experimental methodology to assess contaminant diffusion in rock mass.
AB  - Monitoring changes in electrical conductivity (EC) of aqueous phase, due to
      contaminant diffusion through porous media, is one of the techniques followed by
      researchers to understand the migration mechanism. However, the contaminant
      diffusion in the rock mass is a slow process and hence detecting small changes in
      conductivity with the help of conventional laboratory conductivity meters is
      quite difficult. With this in view, an experimental methodology to monitor
      diffusion of contaminant(s) through the intact and fractured rock mass, with the
      help of a USDTS (Ultra-Sensitive Devices and Technical Services) conductivity
      meter, has been developed. Results have been validated with those obtained from
      the ion chromatograph (IC) technique and a good agreement has been noted. The
      study demonstrates usefulness of the proposed methodology for online monitoring
      of contaminant migration through the porous media.

PMID- 14969450
TI  - A comparative study on the archives of xanthine oxidase and aldehyde oxidase in
      different fish species from two rivers in the Western Niger-Delta.
AB  - Glycaemia, a classical indicator of stress, xanthine oxidase and aldehyde oxidase
      which are involved in phase I detoxication were investigated in two different
      fish species from two rivers with different pollution levels in the Western Niger
      Delta. Four sampling zones covering the entire lengths of Warri and Ethiope
      Rivers respectively were used in this study. For each species of fish five were
      obtained from a sampling zone in a river. Blood glucose was significantly higher
      (P < 0.001) in M. electricus from Warri River (82.13 +/- 5.50 mg cm(-3)) compared
      to the same species from Ethiope River (36.47 +/- 1.49 mg cm(-3)). With the same
      parameter a similar profile was observed for C. gariepinus; Warri River (56.92 +/
      10.31 mg cm(-3)); Ethiope River (37.65 +/- 0.90 mg cm(-3)) which was also
      significant (P < 0.01). The activity of xanthine oxidase in M. electricus from
      Warri River (255.80 +/- 41 it mol cm(-3)) was significantly higher (P < 0.001)
      compared to the value obtained for the same species (108 +/- 22.36 micro mol cm(
      3)) from Ethiope River. Also the activity of xanthine oxidase in C. gariepinus
      from Warri River (197 +/- 34.65 micro mol cm(-3)) was significantly higher (P <
      0.001) when matched with the value obtained for the same species (78.40 +/- 26.84
      micro mol cm(-3)) from Ethiope River. That blood glucose level was related to
      xanthine oxidase activity in the two fish species from Warri River was supported
      by the high positive correlation between these two parameters (M. electricus. r =
      1: C. gariepinus, r = 0.71). The activity of aldehyde oxidase in C. gariepinus
      from Warri River (143.80 +/- 28.45 micro mol cm(-3)) was significantly higher (P
      < 0.001) compared to the value obtained for the same species (61.20 +/- 15.21
      micro mol cm(-3)) from Ethiope River. A similar profile in aldehyde oxidase
      activity observed for M. electricus; Warri River (130 +/- 28.39 micro mol cm(
      3)); Ethiope River (89 +/- 19.70 micro mol cm(-3)) but an inferior statistical
      variation (P < 0.05) was obtained. The results obtained in this study indicate
      that the level of xanthine oxidase in M. electricus is a more specific marker and
      to a lesser extent its activity in C. gariepinus in monitoring environmental
      stress due to pollution.

PMID- 14969451
TI  - Diagnostics for joint longitudinal and dropout time modeling.
AB  - We present a variety of informal graphical procedures for diagnostic assessment
      of joint models for longitudinal and dropout time data. A random effects approach
      for Gaussian responses and proportional hazards dropout time is assumed. We
      consider preliminary assessment of dropout classification categories based on
      residuals following a standard longitudinal data analysis with no allowance for
      informative dropout. Residual properties conditional upon dropout information are
      discussed and case influence is considered. The proposed methods do not require
      computationally intensive methods over and above those used to fit the proposed
      model. A longitudinal trial into the treatment of schizophrenia is used to
      illustrate the suggestions.

PMID- 14969452
TI  - Testing for spatial correlation in nonstationary binary data, with application to
      aberrant crypt foci in colon carcinogenesis.
AB  - In an experiment to understand colon carcinogenesis, all animals were exposed to
      a carcinogen, with half the animals also being exposed to radiation. Spatially,
      we measured the existence of what are referred to as aberrant crypt foci (ACF),
      namely, morphologically changed colonic crypts that are known to be precursors of
      colon cancer development. The biological question of interest is whether the
      locations of these ACFs are spatially correlated: if so, this indicates that
      damage to the colon due to carcinogens and radiation is localized. Statistically,
      the data take the form of binary outcomes (corresponding to the existence of an
      ACF) on a regular grid. We develop score-type methods based upon the Matern and
      conditionally autoregressive (CAR) correlation models to test for the spatial
      correlation in such data, while allowing for nonstationarity. Because of a
      technical peculiarity of the score-type test, we also develop robust versions of
      the method. The methods are compared to a generalization of Moran's test for
      continuous outcomes, and are shown via simulation to have the potential for
      increased power. When applied to our data, the methods indicate the existence of
      spatial correlation, and hence indicate localization of damage.

PMID- 14969453
TI  - Random effects selection in linear mixed models.
AB  - We address the important practical problem of how to select the random effects
      component in a linear mixed model. A hierarchical Bayesian model is used to
      identify any random effect with zero variance. The proposed approach
      reparameterizes the mixed model so that functions of the covariance parameters of
      the random effects distribution are incorporated as regression coefficients on
      standard normal latent variables. We allow random effects to effectively drop out
      of the model by choosing mixture priors with point mass at zero for the random
      effects variances. Due to the reparameterization, the model enjoys a
      conditionally linear structure that facilitates the use of normal conjugate
      priors. We demonstrate that posterior computation can proceed via a simple and
      efficient Markov chain Monte Carlo algorithm. The methods are illustrated using
      simulated data and real data from a study relating prenatal exposure to
      polychlorinated biphenyls and psychomotor development of children.

PMID- 14969454
TI  - Flexible implementations of group sequential stopping rules using constrained
      boundaries.
AB  - Group sequential stopping rules are often used during the conduct of clinical
      trials in order to attain more ethical treatment of patients and to better
      address efficiency concerns. Because the use of such stopping rules materially
      affects the frequentist operating characteristics of the hypothesis test, it is
      necessary to choose an appropriate stopping rule during the planning of the
      study. It is often the case, however, that the number and timing of interim
      analyses are not precisely known at the time of trial design, and thus the
      implementation of a particular stopping rule must allow for flexible
      determination of the schedule of interim analyses. In this article, we consider
      the use of constrained stopping boundaries in the implementation of stopping
      rules. We compare this approach when used on various scales for the test
      statistic. When implemented on the scale of boundary crossing probabilities, this
      approach is identical to the error spending function approach of Lan and DeMets
      (1983).

PMID- 14969455
TI  - Demographic analysis from summaries of an age-structured population.
AB  - Demographic analyses of age-structured populations typically rely on life history
      data for individuals, or when individual animals are not identified, on
      information about the numbers of individuals in each age class through time.
      While it is usually difficult to determine the age class of a randomly
      encountered individual, it is often the case that the individual can be readily
      and reliably assigned to one of a set of age classes. For example, it is often
      possible to distinguish first-year from older birds. In such cases, the
      population age structure can be regarded as a latent variable governed by a
      process prior, and the data as summaries of this latent structure. In this
      article, we consider the problem of uncovering the latent structure and
      estimating process parameters from summaries of age class information. We present
      a demographic analysis for the critically endangered migratory population of
      whooping cranes (Grus americana), based only on counts of first-year birds and of
      older birds. We estimate age and year-specific survival rates. We address the
      controversial issue of whether management action on the breeding grounds has
      influenced recruitment, relating recruitment rates to the number of seventh-year
      and older birds, and examining the pattern of variation through time in this
      rate.

PMID- 14969456
TI  - Open capture-recapture models with heterogeneity: I. Cormack-Jolly-Seber model.
AB  - In open population capture-recapture studies, it is usually assumed that similar
      animals (e.g., of the same sex and age group) have similar survival rates and
      capture probabilities. These assumptions are generally perceived to be an
      oversimplification, and they can lead to incorrect model selection and biased
      parameter estimates. Allowing for individual variability in survival and capture
      probabilities among apparently similar animals is now becoming possible, due to
      advances in closed population models and improved computing power. This article
      presents a flexible framework of likelihood-based models which allow for
      individual heterogeneity in survival and capture rates. Heterogeneity is modeled
      using finite mixtures, which have enough flexibility of distribution shape to
      accommodate a wide variety of different patterns of individual variation. The
      models condition on the first capture of each animal, and include as a special
      case the Cormack-Jolly-Seber model. Model selection is done either using Akaike's
      information criterion or by likelihood ratio tests, making available checks of
      different influences on survival rates. Bias in parameter estimates is reduced by
      including individual heterogeneity. Model selection and bias reduction are
      important in population studies and for making informed management decisions.

PMID- 14969457
TI  - Joint regression and association modeling of longitudinal ordinal data.
AB  - We propose models for longitudinal, or otherwise clustered, ordinal data. The
      association between subunit responses is characterized by dependence ratios
      (Ekholm, Smith, and McDonald, 1995, Biometrika 82, 847-854), which are extended
      from the binary to the multicategory case. The joint probabilities of the subunit
      responses are expressed as explicit functions of the marginal means and the
      dependence ratios of all orders, obtaining a computational advantage for
      likelihood-based inference. Equal emphasis is put on finding regression models
      for the univariate cumulative probabilities, and on deriving the dependence
      ratios from meaningful association-generating mechanisms. A data set on the
      effects of treatment with Fluvoxamine, which has been analyzed in parts before
      (Molenberghs, Kenward, and Lesaffre, 1997, Biometrika 84, 33-44), is analyzed in
      its entirety. Selection models are used for studying the sensitivity of the
      results to drop-out.

PMID- 14969458
TI  - Shape-invariant modeling of circadian rhythms with random effects and smoothing
      spline ANOVA decompositions.
AB  - Medical studies often collect physiological and/or psychological measurements
      over time from multiple subjects, to study dynamics such as circadian rhythms.
      Under the assumption that the expected response functions of all subjects are the
      same after shift and scale transformations, shape-invariant models have been
      applied to analyze this kind of data. The shift and scale parameters provide
      efficient and interpretable data summaries, while the common shape function is
      usually modeled nonparametrically, to provide flexibility. However, due to the
      deterministic nature of the shift and scale parameters, potential correlations
      within a subject are ignored. Furthermore, the shape of the common function may
      depend on other factors, such as disease. In this article, we propose shape
      invariant mixed effects models. A second-stage model with fixed and random
      effects is used to model individual shift and scale parameters. A second-stage
      smoothing spline ANOVA model is used to study potential covariate effects on the
      common shape function. We apply our methods to a real data set to investigate
      disease effects on circadian rhythms of cortisol, a hormone that is affected by
      stress. We find that patients with Cushing's syndrome lost circadian rhythms and
      their 24-hour means were elevated to very high levels. Patients with major
      depression had the same circadian shape and phases as normal subjects. However,
      their 24-hour mean levels were elevated and amplitudes were dampened for some
      patients.

PMID- 14969459
TI  - Smoothing for spatiotemporal models and its application to modeling muskrat-mink
      interaction.
AB  - For a set of spatially dependent dynamical models, we propose a method for
      estimating parameters that control temporal dynamics by spatial smoothing. The
      new approach is particularly relevant for analyzing spatially distributed panels
      of short time series. The asymptotic results show that spatial smoothing will
      improve the estimation in the presence of nugget effect, even when the sample
      size in each location is large. The proposed methodology is used to analyze the
      annual mink and muskrat data collected in a period of 25 years in 81 Canadian
      locations. Based on the proposed method, we are able to model the temporal
      dynamics which reflects the food chain interaction of the two species.

PMID- 14969460
TI  - Design considerations for efficient and effective microarray studies.
AB  - This article describes the theoretical and practical issues in experimental
      design for gene expression microarrays. Specifically, this article 1) discusses
      the basic principles of design (randomization, replication, and blocking) as they
      pertain to microarrays, and 2) provides some general guidelines for statisticians
      designing microarray studies.

PMID- 14969461
TI  - Modeling longitudinal data with nonignorable dropouts using a latent dropout
      class model.
AB  - In longitudinal studies with dropout, pattern-mixture models form an attractive
      modeling framework to account for nonignorable missing data. However, pattern
      mixture models assume that the components of the mixture distribution are
      entirely determined by the dropout times. That is, two subjects with the same
      dropout time have the same distribution for their response with probability one.
      As that is unlikely to be the case, this assumption made lead to classification
      error. In addition, if there are certain dropout patterns with very few subjects,
      which often occurs when the number of observation times is relatively large,
      pattern-specific parameters may be weakly identified or require identifying
      restrictions. We propose an alternative approach, which is a latent-class model.
      The dropout time is assumed to be related to the unobserved (latent) class
      membership, where the number of classes is less than the number of observed
      patterns; a regression model for the response is specified conditional on the
      latent variable. This is a type of shared-parameter model, where the shared
      "parameter" is discrete. Parameter estimates are obtained using the method of
      maximum likelihood. Averaging the estimates of the conditional parameters over
      the distribution of the latent variable yields estimates of the marginal
      regression parameters. The methodology is illustrated using longitudinal data on
      depression from a study of HIV in women.

PMID- 14969462
TI  - Flexible maximum likelihood methods for bivariate proportional hazards models.
AB  - This article presents methodology for multivariate proportional hazards (PH)
      regression models. The methods employ flexible piecewise constant or spline
      specifications for baseline hazard functions in either marginal or conditional PH
      models, along with assumptions about the association among lifetimes. Because the
      models are parametric, ordinary maximum likelihood can be applied; it is able to
      deal easily with such data features as interval censoring or sequentially
      observed lifetimes, unlike existing semiparametric methods. A bivariate Clayton
      model (1978, Biometrika 65, 141-151) is used to illustrate the approach taken.
      Because a parametric assumption about association is made, efficiency and
      robustness comparisons are made between estimation based on the bivariate Clayton
      model and "working independence" methods that specify only marginal distributions
      for each lifetime variable.

PMID- 14969463
TI  - Estimating the generalized concordance correlation coefficient through variance
      components.
AB  - The intraclass correlation coefficient (ICC) and the concordance correlation
      coefficient (CCC) are two of the most popular measures of agreement for variables
      measured on a continuous scale. Here, we demonstrate that ICC and CCC are the
      same measure of agreement estimated in two ways: by the variance components
      procedure and by the moment method. We propose estimating the CCC using variance
      components of a mixed effects model, instead of the common method of moments.
      With the variance components approach, the CCC can easily be extended to more
      than two observers, and adjusted using confounding covariates, by incorporating
      them in the mixed model. A simulation study is carried out to compare the
      variance components approach with the moment method. The importance of adjusting
      by confounding covariates is illustrated with a case example.

PMID- 14969464
TI  - Inference in spline-based models for multiple time-to-event data, with
      applications to a breast cancer prevention trial.
AB  - As part of the National Surgical Adjuvant Breast and Bowel Project, a controlled
      clinical trial known as the Breast Cancer Prevention Trial (BCPT) was conducted
      to assess the effectiveness of tamoxifen as a preventive agent for breast cancer.
      In addition to the incidence of breast cancer, data were collected on several
      other, possibly adverse, outcomes, such as invasive endometrial cancer, ischemic
      heart disease, transient ischemic attack, deep vein thrombosis and/or pulmonary
      embolism. In this article, we present results from an illustrative analysis of
      the BCPT data, based on a new modeling technique, to assess the effectiveness of
      the drug tamoxifen as a preventive agent for breast cancer. We extended the
      flexible model of Gray (1994, Spline-based test in survival analysis, Biometrics
      50, 640-652) to allow inference on multiple time-to-event outcomes in the style
      of the marginal modeling setup of Wei, Lin, and Weissfeld (1989, Regression
      analysis of multivariate incomplete failure time data by modeling marginal
      distributions, Journal of the American Statistical Association 84, 1065-1073).
      This proposed model makes inference possible for multiple time-to-event data
      while allowing for greater flexibility in modeling the effects of prognostic
      factors with nonlinear exposure-response relationships. Results from simulation
      studies on the small-sample properties of the asymptotic tests will also be
      presented.

PMID- 14969465
TI  - Semiparametric estimation of tag loss and reporting rates for tag-recovery
      experiments using exact time-at-liberty data.
AB  - We present a semiparametric likelihood approach to estimating reporting rates and
      tag-loss rates from the tags returned from capture-recapture studies. Such
      studies are commonly used to estimate critical population parameters. Tag loss
      rates are estimated using double-tagged animals, while reporting rates are
      estimated using information from high-reward tags. A likelihood function is
      constructed based on the conditional distribution of the type of tag returned
      (low or high reward, single or double tag), given that a tag has been returned.
      This involves many sparse 5 x 1 tag-return contingency tables, and choosing a
      good functional form for the tag loss rate is difficult with such data. We model
      tag-loss rates using monotone-smoothing splines, and use these nonparametric
      estimates to diagnose the parametric form of the tag-loss rate. The nonparametric
      methods can also be used directly to model tag-loss rates.

PMID- 14969466
TI  - Semiparametric analysis of recurrent events data in the presence of dependent
      censoring.
AB  - Dependent censoring occurs in longitudinal studies of recurrent events when the
      censoring time depends on the potentially unobserved recurrent event times. To
      perform regression analysis in this setting, we propose a semiparametric joint
      model that formulates the marginal distributions of the recurrent event process
      and dependent censoring time through scale-change models, while leaving the
      distributional form and dependence structure unspecified. We derive consistent
      and asymptotically normal estimators for the regression parameters. We also
      develop graphical and numerical methods for assessing the adequacy of the
      proposed model. The finite-sample behavior of the new inference procedures is
      evaluated through simulation studies. An application to recurrent hospitalization
      data taken from a study of intravenous drug users is provided.

PMID- 14969467
TI  - A Bayesian hierarchical model for categorical data with nonignorable nonresponse.
AB  - Log-linear models have been shown to be useful for smoothing contingency tables
      when categorical outcomes are subject to nonignorable nonresponse. A log-linear
      model can be fit to an augmented data table that includes an indicator variable
      designating whether subjects are respondents or nonrespondents. Maximum
      likelihood estimates calculated from the augmented data table are known to suffer
      from instability due to boundary solutions. Park and Brown (1994, Journal of the
      American Statistical Association 89, 44-52) and Park (1998, Biometrics 54, 1579
      1590) developed empirical Bayes models that tend to smooth estimates away from
      the boundary. In those approaches, estimates for nonrespondents were calculated
      using an EM algorithm by maximizing a posterior distribution. As an extension of
      their earlier work, we develop a Bayesian hierarchical model that incorporates a
      log-linear model in the prior specification. In addition, due to uncertainty in
      the variable selection process associated with just one log-linear model, we
      simultaneously consider a finite number of models using a stochastic search
      variable selection (SSVS) procedure due to George and McCulloch (1997, Statistica
      Sinica 7, 339-373). The integration of the SSVS procedure into a Markov chain
      Monte Carlo (MCMC) sampler is straightforward, and leads to estimates of cell
      frequencies for the nonrespondents that are averages resulting from several log
      linear models. The methods are demonstrated with a data example involving serum
      creatinine levels of patients who survived renal transplants. A simulation study
      is conducted to investigate properties of the model.

PMID- 14969468
TI  - Modeling tumor growth with random onset.
AB  - The longitudinal assessment of tumor volume is commonly used as an endpoint in
      small animal studies in cancer research. Groups of genetically identical mice are
      injected with mutant cells from clones developed with different mutations. The
      interest is on comparing tumor onset (i.e., the time of tumor detection) and
      tumor growth after onset, between mutation groups. This article proposes a class
      of linear and nonlinear growth models for jointly modeling tumor onset and growth
      in this situation. Our approach allows for interval-censored time of onset and
      missing-at-random dropout due to early sacrifice, which are common situations in
      animal research. We show that our approach has good small-sample properties for
      testing and is robust to some key unverifiable modeling assumptions. We
      illustrate this methodology with an application examining the effect of different
      mutations on tumorigenesis.

PMID- 14969469
TI  - Profile analysis of 24-hours measurements of blood pressure.
AB  - A method is proposed for classifying subjects according to their convex, flat, or
      concave change patterns of 24-hours blood pressure measurements. To obtain such a
      classification is useful for detecting subjects who show abnormal change patterns
      and giving them appropriate medical treatments. Therefore, an appropriate
      statistic is proposed for detecting a systematic change along the time axis, as
      well as a statistic with its inverse characteristic appropriate for evaluating
      the noise variation. The method is based on the ratio of those two types of
      statistics; it is verified to work well on real data, giving a classification of
      subjects into four types of subgroups: extreme dipper, dipper, nondipper, and
      inverted dipper. It also suggests that there might be an ultra-extreme dipper
      subgroup.

PMID- 14969470
TI  - Bayesian inferences in the Cox model for order-restricted hypotheses.
AB  - In studying the relationship between an ordered categorical predictor and an
      event time, it is standard practice to include dichotomous indicators of the
      different levels of the predictor in a Cox model. One can then use a multiple
      degree-of-freedom score or partial likelihood ratio test for hypothesis testing.
      Often, interest focuses on comparing the null hypothesis of no difference to an
      order-restricted alternative, such as a monotone increase across levels of a
      predictor. This article proposes a Bayesian approach for addressing hypotheses of
      this type. We reparameterize the Cox model in terms of a cumulative product of
      parameters having conjugate prior densities, consisting of mixtures of point
      masses at one, and truncated gamma densities. Due to the structure of the model,
      posterior computation can proceed via a simple and efficient Gibbs sampling
      algorithm. Posterior probabilities for the global null hypothesis and
      subhypotheses, comparing the hazards for specific groups, can be calculated
      directly from the output of a single Gibbs chain. The approach allows for level
      sets across which a predictor has no effect. Generalizations to multiple
      predictors are described, and the method is applied to a study of emergency
      medical treatment for stroke.

PMID- 14969471
TI  - Incorporating covariates into standard line transect analyses.
AB  - An implicit assumption of standard line transect methodology is that detection
      probabilities depend solely on the perpendicular distance of detected objects to
      the transect line. Heterogeneity in detection probabilities is commonly minimized
      using stratification, but this may be precluded by small sample sizes. We develop
      a general methodology which allows the effects of multiple covariates to be
      directly incorporated into the estimation procedure using a conditional
      likelihood approach. Small sample size properties of estimators are examined via
      simulations. As an example the method is applied to eastern tropical Pacific
      dolphin sightings data.

PMID- 14969472
TI  - Meta-analysis of diagnostic test accuracy assessment studies with varying number
      of thresholds.
AB  - Current meta-analytic methods for diagnostic test accuracy are generally
      applicable to a selection of studies reporting only estimates of sensitivity and
      specificity, or at most, to studies whose results are reported using an equal
      number of ordered categories. In this article, we propose a new meta-analytic
      method to evaluate test accuracy and arrive at a summary receiver operating
      characteristic (ROC) curve for a collection of studies evaluating diagnostic
      tests, even when test results are reported in an unequal number of nonnested
      ordered categories. We discuss both non-Bayesian and Bayesian formulations of the
      approach. In the Bayesian setting, we propose several ways to construct summary
      ROC curves and their credible bands. We illustrate our approach with data from a
      recently published meta-analysis evaluating a single serum progesterone test for
      diagnosing pregnancy failure.

PMID- 14969473
TI  - Discrete proportional hazards models for mismeasured outcomes.
AB  - Outcome mismeasurement can lead to biased estimation in several contexts. Magder
      and Hughes (1997, American Journal of Epidemiology 146, 195-203) showed that
      failure to adjust for imperfect outcome measures in logistic regression analysis
      can conservatively bias estimation of covariate effects, even when the
      mismeasurement rate is the same across levels of the covariate. Other authors
      have addressed the need to account for mismeasurement in survival analysis in
      selected cases (Snapinn, 1998, Biometrics 54, 209-218; Gelfand and Wang, 2000,
      Statistics in Medicine 19, 1865-1879; Balasubramanian and Lagakos, 2001,
      Biometrics 57, 1048-1058, 2003, Biometrika 90, 171-182). We provide a general,
      more widely applicable, adjusted proportional hazards (APH) method for estimation
      of cumulative survival and hazard ratios in discrete time when the outcome is
      measured with error. We show that mismeasured failure status in a standard
      proportional hazards (PH) model can conservatively bias estimation of hazard
      ratios and that inference, in most practical situations, is more severely
      affected by poor specificity than by poor sensitivity. However, in simulations
      over a wide range of conditions, the APH method with correctly specified
      mismeasurement rates performs very well.

PMID- 14969474
TI  - Modeling the dependence between number of trials and success probability in beta
      binomial-Poisson mixture distributions.
AB  - Beta-binomial models are widely used for overdispersed binomial data, with the
      binomial success probability modeled as following a beta distribution. The number
      of binary trials in each binomial is assumed to be nonrandom and unrelated to the
      success probability. In many behavioral studies, however, binomial observations
      demonstrate more complex structures. In this article, a general beta-binomial
      Poisson mixture model is developed, to allow for a relation between the number of
      trials and the success probability for overdispersed binomial data. An EM
      algorithm is implemented to compute both the maximum likelihood estimates of the
      model parameters and the corresponding standard errors. For illustration, the
      methodology is applied to study the feeding behavior of green-backed herons in
      two southeastern Missouri streams.

PMID- 14969475
TI  - Bayesian modeling of age-specific survival in bird nesting studies under
      irregular visits.
AB  - In this article, a Bayesian model for age-specific nest survival rates is
      presented to handle the irregular visit case. Both informative priors and
      noninformative priors are investigated. The reference prior under this model is
      derived, and, therefore, the hyperparameter specification problem is solved to
      some extent. The Bayesian method provides a more accurate estimate of the total
      survival rate than the standard Mayfield method, if the age-specific hazard rates
      are not constant. The Bayesian method also lets the biologist look for high- and
      low-survival rates during the whole nesting period. In practice, it is common for
      data of several types to be collected in a single study. That is, some nests may
      be aged, others are not. Some nests are visited regularly; others are visited
      irregularly. The Bayesian method accommodates any mix of these sampling
      techniques by assuming that the aging and visiting activities have no effect on
      the survival rate. The methods are illustrated by an analysis of the Missouri
      northern bobwhite data set.

PMID- 14969476
TI  - Abundance estimation from multiple photo surveys: confidence distributions and
      reduced likelihoods for bowhead whales off Alaska.
AB  - Maximum likelihood estimates of abundance are obtained from repeated photographic
      surveys of a closed stratified population with naturally marked and unmarked
      individuals. Capture intensities are assumed log-linear in stratum, year, and
      season. In the chosen model, an approximate confidence distribution for total
      abundance of bowhead whales, with an accompanying likelihood reduced of nuisance
      parameters, is found from a parametric bootstrap experiment. The confidence
      distribution depends on the assumed study protocol. A confidence distribution
      that is exact (except for the effect of discreteness) is found by conditioning in
      the unstratified case without unmarked individuals.

PMID- 14969477
TI  - Using local correlation in kernel-based smoothers for dependent data.
AB  - We consider the general problem of smoothing correlated data to estimate the
      nonparametric mean function when a random, but bounded, number of measurements is
      available for each independent subject. We propose a simple extension to the
      local polynomial regression smoother that retains the asymptotic properties of
      the working independence estimator, while typically reducing both the conditional
      bias and variance for practical sample sizes, as demonstrated by exact
      calculations for some particular models. We illustrate our method by smoothing
      longitudinal functional decline data for 100 patients with Huntington's disease.
      The class of local polynomial kernel-based estimating equations previously
      considered in the literature is shown to use the global correlation structure in
      an apparently detrimental way, which explains why some previous attempts to
      incorporate correlation were found to be asymptotically inferior to the working
      independence estimator.

PMID- 14969478
TI  - Penalized discriminant methods for the classification of tumors from gene
      expression data.
AB  - Due to the advent of high-throughput microarray technology, it has become
      possible to develop molecular classification systems for various types of cancer.
      In this article, we propose a methodology using regularized regression models for
      the classification of tumors in microarray experiments. The performances of
      principal components, partial least squares, and ridge regression models are
      studied; these regression procedures are adapted to the classification setting
      using the optimal scoring algorithm. We also develop a procedure for ranking
      genes based on the fitted regression models. The proposed methodologies are
      applied to two microarray studies in cancer.

PMID- 14969479
TI  - A new dose-finding design for bivariate outcomes.
AB  - For some drugs, toxicity events lead to early termination of treatment before a
      therapeutic response is observed. That is, there are three possible outcomes:
      toxicity (therapeutic response unknown), therapeutic response without toxicity,
      and no response with no toxicity. The optimal dose is the dose that maximizes the
      probability of the joint event, response, and no toxicity. The optimal safe dose
      is the dose, from among the doses with toxicity rate less than the maximum
      tolerable level, that maximizes the probability of response and no toxicity. We
      present a new sequential design to maximize the number of subjects assigned in
      the neighborhood of the optimal safe dose in a dose-finding trial with two
      outcomes.

PMID- 14969480
TI  - Estimating predictors for long- or short-term survivors.
AB  - Suppose that the response variable in a well-executed clinical or observational
      study to evaluate a treatment is the time to a certain event, and a set of
      baseline covariates or predictors was collected for each study patient.
      Furthermore, suppose that a significant number of study patients had nontrivial,
      long-term adverse effects from the treatment. A commonly posed question is how to
      use these covariates from the study to identify future patients who would (or
      would not) benefit from the treatment. In this article, we present "point" and
      "interval" estimates for the set of covariate or predictor vectors associated
      with a specific patient survival status, e.g., long- (or short-) term survival,
      in the presence of censoring. These estimates can be easily displayed on a two
      dimensional plane, even for the case with high-dimensional covariate vectors.
      These simple numerical and graphical procedures provide useful information for
      patient management and/or the design of future studies, which are key issues in
      pharmacogenomics with genetic markers. The new proposal is illustrated with a
      data set from a cancer study for treating multiple myeloma.

PMID- 14969481
TI  - Minimum Hellinger distance estimation for finite mixtures of Poisson regression
      models and its applications.
AB  - Minimum Hellinger distance estimation (MHDE) has been shown to discount anomalous
      data points in a smooth manner with first-order efficiency for a correctly
      specified model. An estimation approach is proposed for finite mixtures of
      Poisson regression models based on MHDE. Evidence from Monte Carlo simulations
      suggests that MHDE is a viable alternative to the maximum likelihood estimator
      when the mixture components are not well separated or the model parameters are
      near zero. Biometrical applications also illustrate the practical usefulness of
      the MHDE method.

PMID- 14969482
TI  - Homogeneity score test for the intraclass version of the kappa statistics and
      sample-size determination in multiple or stratified studies.
AB  - When the intraclass correlation coefficient or the equivalent version of the
      kappa agreement coefficient have been estimated from several independent studies
      or from a stratified study, we have the problem of comparing the kappa statistics
      and combining the information regarding the kappa statistics in a common kappa
      when the assumption of homogeneity of kappa coefficients holds. In this article,
      using the likelihood score theory extended to nuisance parameters (Tarone, 1988,
      Communications in Statistics-Theory and Methods 17(5), 1549-1556) we present an
      efficient homogeneity test for comparing several independent kappa statistics
      and, also, give a modified homogeneity score method using a noniterative and
      consistent estimator as an alternative. We provide the sample size using the
      modified homogeneity score method and compare it with that using the goodness-of
      fit method (GOF) (Donner, Eliasziw, and Klar, 1996, Biometrics 52, 176-183). A
      simulation study for small and moderate sample sizes showed that the actual level
      of the homogeneity score test using the maximum likelihood estimators (MLEs) of
      parameters is satisfactorily close to the nominal and it is smaller than those of
      the modified homogeneity score and the goodness-of-fit tests. We investigated
      statistical properties of several noniterative estimators of a common kappa. The
      estimator (Donner et al., 1996) is essentially efficient and can be used as an
      alternative to the iterative MLE. An efficient interval estimation of a common
      kappa using the likelihood score method is presented.

PMID- 14969483
TI  - Extensions and applications of the Cox-Aalen survival model.
AB  - Cox's regression model is the standard regression tool for survival analysis in
      most applications. Often, however, the model only provides a rough summary of the
      effect of some covariates. Therefore, if the aim is to give a detailed
      description of covariate effects and to consequently calculate predicted
      probabilities, more flexible models are needed. In another article, Scheike and
      Zhang (2002, Scandinavian Journal of Statistics 29, 75-88), we suggested a
      flexible extension of Cox's regression model, which aimed at extending the Cox
      model only for those covariates where additional flexibility are needed. One
      important advantage of the suggested approach is that even though covariates are
      allowed a nonparametric effect, the hassle and difficulty of finding smoothing
      parameters are not needed. We show how the extended model also leads to simple
      formulae for predicted probabilities and their standard errors, for example, in
      the competing risk framework.

PMID- 14969484
TI  - Semiparametric estimation of treatment effect in a pretest-posttest study.
AB  - Inference on treatment effects in a pretest-posttest study is a routine objective
      in medicine, public health, and other fields. A number of approaches have been
      advocated. We take a semiparametric perspective, making no assumptions about the
      distributions of baseline and posttest responses. By representing the situation
      in terms of counterfactual random variables, we exploit recent developments in
      the literature on missing data and causal inference, to derive the class of all
      consistent treatment effect estimators, identify the most efficient such
      estimator, and outline strategies for implementation of estimators that may
      improve on popular methods. We demonstrate the methods and their properties via
      simulation and by application to a data set from an HIV clinical trial.

PMID- 14969485
TI  - Confidence bands for low-dose risk estimation with quantal response data.
AB  - We study the use of simultaneous confidence bands for low-dose risk estimation
      with quantal response data, and derive methods for estimating simultaneous upper
      confidence limits on predicted extra risk under a multistage model. By inverting
      the upper bands on extra risk, we obtain simultaneous lower bounds on the
      benchmark dose (BMD). Monte Carlo evaluations explore characteristics of the
      simultaneous limits under this setting, and a suite of actual data sets are used
      to compare existing methods for placing lower limits on the BMD.

PMID- 14969486
TI  - Estimation of competing risks with general missing pattern in failure types.
AB  - In competing risks data, missing failure types (causes) is a very common
      phenomenon. In this work, we consider a general missing pattern in which, if a
      failure type is not observed, one observes a set of possible types containing the
      true type, along with the failure time. We first consider maximum likelihood
      estimation with missing-at-random assumption via the expectation maximization
      (EM) algorithm. We then propose a Nelson-Aalen type estimator for situations when
      certain information on the conditional probability of the true type given a set
      of possible failure types is available from the experimentalists. This is based
      on a least-squares type method using the relationships between hazards for
      different types and hazards for different combinations of missing types. We
      conduct a simulation study to investigate the performance of this method, which
      indicates that bias may be small, even for high proportion of missing data, for
      sufficiently large number of observations. The estimates are somewhat sensitive
      to misspecification of the conditional probabilities of the true types when the
      missing proportion is high. We also consider an example from an animal experiment
      to illustrate our methodology.

PMID- 14969487
TI  - Estimation of false discovery rates in multiple testing: application to gene
      microarray data.
AB  - Testing for significance with gene expression data from DNA microarray
      experiments involves simultaneous comparisons of hundreds or thousands of genes.
      If R denotes the number of rejections (declared significant genes) and V denotes
      the number of false rejections, then V/R, if R > 0, is the proportion of false
      rejected hypotheses. This paper proposes a model for the distribution of the
      number of rejections and the conditional distribution of V given R, V / R. Under
      the independence assumption, the distribution of R is a convolution of two
      binomials and the distribution of V / R has a noncentral hypergeometric
      distribution. Under an equicorrelated model, the distributions are more complex
      and are also derived. Five false discovery rate probability error measures are
      considered: FDR = E(V/R), pFDR = E(V/R / R > 0) (positive FDR), cFDR = E(V/R / R
      = r) (conditional FDR), mFDR = E(V)/E(R) (marginal FDR), and eFDR = E(V)/r
      (empirical FDR). The pFDR, cFDR, and mFDR are shown to be equivalent under the
      Bayesian framework, in which the number of true null hypotheses is modeled as a
      random variable. We present a parametric and a bootstrap procedure to estimate
      the FDRs. Monte Carlo simulations were conducted to evaluate the performance of
      these two methods. The bootstrap procedure appears to perform reasonably well,
      even when the alternative hypotheses are correlated (rho = .25). An example from
      a toxicogenomic microarray experiment is presented for illustration.

PMID- 14969488
TI  - A Bayesian A-optimal and model robust design criterion.
AB  - Suppose that the true model underlying a set of data is one of a finite set of
      candidate models, and that parameter estimation for this model is of primary
      interest. With this goal, optimal design must depend on a loss function across
      all possible models. A common method that accounts for model uncertainty is to
      average the loss over all models; this is the basis of what is known as Lauter's
      criterion. We generalize Lauter's criterion and show that it can be placed in a
      Bayesian decision theoretic framework, by extending the definition of Bayesian A
      optimality. We use this generalized A-optimality to find optimal design points in
      an environmental safety setting. In estimating the smallest detectable trace
      limit in a water contamination problem, we obtain optimal designs that are quite
      different from those suggested by standard A-optimality.

PMID- 14969489
TI  - Incorporation of clustering effects for the Wilcoxon rank sum test: a large
      sample approach.
AB  - The Wilcoxon rank sum test is frequently used in statistical practice for the
      comparison of measures of location when the underlying distributions are far from
      normal or not known in advance. An assumption of the ordinary rank sum test is
      that individual sampling units are independent. In many ophthalmologic clinical
      trials, the Early Treatment for Diabetic Retinopathy Scale (ETDRS) is a principal
      endpoint used for measuring the level of diabetic retinopathy. This is an ordinal
      scale, and it is natural to consider the Wilcoxon rank sum test for the
      comparison of the level of diabetic retinopathy between treatment groups.
      However, under this design, unlike the usual Wilcoxon rank sum test, the subject
      is the unit of randomization, but the eye is the unit of analysis. Furthermore, a
      person will tend to have different, but correlated, ETDRS scores for fellow eyes.
      Thus, we propose a correction to the variance of the Wilcoxon rank sum statistic
      that accounts for clustering effects and that can be used for both balanced (same
      number of subunits per cluster) or unbalanced (different number of subunits per
      cluster) data, both in the presence or absence of ties, with p-value adjusted
      accordingly. In this article, we present large-sample theory and simulation
      results for this test procedure and apply it to diabetic retinopathy data from
      type I diabetics in the Sorbinil Retinopathy Trial.

PMID- 14969490
TI  - The gamma-frailty Poisson model for the nonparametric estimation of panel count
      data.
AB  - In this article, we study nonparametric estimation of the mean function of a
      counting process with panel observations. We introduce the gamma frailty variable
      to account for the intracorrelation between the panel counts of the counting
      process and construct a maximum pseudo-likelihood estimate with the frailty
      variable. Three simulated examples are given to show that this estimation
      procedure, while preserving the robustness and simplicity of the computation,
      improves the efficiency of the nonparametric maximum pseudo-likelihood estimate
      studied in Wellner and Zhang (2000, Annals of Statistics 28, 779-814). A real
      example from a bladder tumor study is used to illustrate the method.

PMID- 14969491
TI  - Issues of cost and efficiency in the design of reliability studies.
AB  - Reliability of continuous and dichotomous responses is usually assessed by means
      of the intraclass correlation coefficient (ICC). We derive the optimal allocation
      of the number of subjects k and the number of repeated measurements n that
      minimize the variance of the estimated ICC. Cost constraints are discussed for
      the case of normally distributed responses. Tables showing optimal choices of k
      and n are given, along with guidelines for the design of reliability studies in
      light of our results and those reported by others.

PMID- 14969492
TI  - Estimation in capture-recapture models when covariates are subject to measurement
      errors.
AB  - We consider estimation problems in capture-recapture models when the covariates
      or the auxiliary variables are measured with errors. The naive approach, which
      ignores measurement errors, is found to be unacceptable in the estimation of both
      regression parameters and population size: it yields estimators with biases
      increasing with the magnitude of errors, and flawed confidence intervals. To
      account for measurement errors, we derive a regression parameter estimator using
      a regression calibration method. We develop modified estimators of the population
      size accordingly. A simulation study shows that the resulting estimators are more
      satisfactory than those from either the naive approach or the simulation
      extrapolation (SIMEX) method. Data from a bird species Prinia flaviventris in
      Hong Kong are analyzed with and without the assumption of measurement errors, to
      demonstrate the effects of errors on estimations.

PMID- 14969493
TI  - Nonidentifiability of population size from capture-recapture data with
      heterogeneous detection probabilities.
AB  - Heterogeneity in detection probabilities has long been recognized as problematic
      in mark-recapture studies, and numerous models developed to accommodate its
      effects. Individual heterogeneity is especially problematic, in that reasonable
      alternative models may predict essentially identical observations from
      populations of substantially different sizes. Thus even with very large samples,
      the analyst will not be able to distinguish among reasonable models of
      heterogeneity, even though these yield quite distinct inferences about population
      size. The problem is illustrated with models for closed and open populations.

PMID- 14969494
TI  - Graphical exploration of gene expression data: a comparative study of three
      multivariate methods.
AB  - This article describes three multivariate projection methods and compares them
      for their ability to identify clusters of biological samples and genes using real
      life data on gene expression levels of leukemia patients. It is shown that
      principal component analysis (PCA) has the disadvantage that the resulting
      principal factors are not very informative, while correspondence factor analysis
      (CFA) has difficulties interpreting distances between objects. Spectral map
      analysis (SMA) is introduced as an alternative approach to the analysis of
      microarray data. Weighted SMA outperforms PCA, and is at least as powerful as
      CFA, in finding clusters in the samples, as well as identifying genes related to
      these clusters. SMA addresses the problem of data analysis in microarray
      experiments in a more appropriate manner than CFA, and allows more flexible
      weighting to the genes and samples. Proper weighting is important, since it
      enables less reliable data to be down-weighted and more reliable information to
      be emphasized.

PMID- 14969495
TI  - Maximum likelihood methods for nonignorable missing responses and covariates in
      random effects models.
AB  - This article analyzes quality of life (QOL) data from an Eastern Cooperative
      Oncology Group (ECOG) melanoma trial that compared treatment with ganglioside
      vaccination to treatment with high-dose interferon. The analysis of this data set
      is challenging due to several difficulties, namely, nonignorable missing
      longitudinal responses and baseline covariates. Hence, we propose a selection
      model for estimating parameters in the normal random effects model with
      nonignorable missing responses and covariates. Parameters are estimated via
      maximum likelihood using the Gibbs sampler and a Monte Carlo expectation
      maximization (EM) algorithm. Standard errors are calculated using the bootstrap.
      The method allows for nonmonotone patterns of missing data in both the response
      variable and the covariates. We model the missing data mechanism and the missing
      covariate distribution via a sequence of one-dimensional conditional
      distributions, allowing the missing covariates to be either categorical or
      continuous, as well as time-varying. We apply the proposed approach to the ECOG
      quality-of-life data and conduct a small simulation study evaluating the
      performance of the maximum likelihood estimates. Our results indicate that a
      patient treated with the vaccine has a higher QOL score on average at a given
      time point than a patient treated with high-dose interferon.

PMID- 14969496
TI  - Exact log-rank tests for unequal follow-up.
AB  - The asymptotic log-rank and generalized Wilcoxon tests are the standard
      procedures for comparing samples of possibly censored survival times. For
      comparison of samples of very different sizes, an exact test is available that is
      based on a complete permutation of log-rank or Wilcoxon scores. While the
      asymptotic tests do not keep their nominal sizes if sample sizes differ
      substantially, the exact complete permutation test requires equal follow-up of
      the samples. Therefore, we have developed and present two new exact tests also
      suitable for unequal follow-up. The first of these is an exact analogue of the
      asymptotic log-rank test and conditions on observed risk sets, whereas the second
      approach permutes survival times while conditioning on the realized follow-up in
      each group. In an empirical study, we compare the new procedures with the
      asymptotic log-rank test, the exact complete permutation test, and an earlier
      proposed approach that equalizes the follow-up distributions using artificial
      censoring. Results confirm highly satisfactory performance of the exact procedure
      conditioning on realized follow-up, particularly in case of unequal follow-up.
      The advantage of this test over other options of analysis is finally exemplified
      in the analysis of a breast cancer study.

PMID- 14969497
TI  - Semiparametric regression splines in matched case-control studies.
AB  - We develop semiparametric methods for matched case-control studies using
      regression splines. Three methods are developed: 1) an approximate cross
      validation scheme to estimate the smoothing parameter inherent in regression
      splines, as well as 2) Monte Carlo expectation maximization (MCEM) and 3)
      Bayesian methods to fit the regression spline model. We compare the approximate
      cross-validation approach, MCEM, and Bayesian approaches using simulation,
      showing that they appear approximately equally efficient; the approximate cross
      validation method is computationally the most convenient. An example from equine
      epidemiology that motivated the work is used to demonstrate our approaches.

PMID- 14969498
TI  - Statistical analysis of noninferiority trials with a rate ratio in small-sample
      matched-pair designs.
AB  - Testing of noninferiority has become increasingly important in modern medicine as
      a means of comparing a new test procedure to a currently available test
      procedure. Asymptotic methods have recently been developed for analyzing
      noninferiority trials using rate ratios under the matched-pair design. In small
      samples, however, the performance of these asymptotic methods may not be
      reliable, and they are not recommended. In this article, we investigate
      alternative methods that are desirable for assessing noninferiority trials, using
      the rate ratio measure under small-sample matched-pair designs. In particular, we
      propose an exact and an approximate exact unconditional test, along with the
      corresponding confidence intervals based on the score statistic. The exact
      unconditional method guarantees the type I error rate will not exceed the nominal
      level. It is recommended for when strict control of type I error (protection
      against any inflated risk of accepting inferior treatments) is required. However,
      the exact method tends to be overly conservative (thus, less powerful) and
      computationally demanding. Via empirical studies, we demonstrate that the
      approximate exact score method, which is computationally simple to implement,
      controls the type I error rate reasonably well and has high power for hypothesis
      testing. On balance, the approximate exact method offers a very good alternative
      for analyzing correlated binary data from matched-pair designs with small sample
      sizes. We illustrate these methods using two real examples taken from a crossover
      study of soft lenses and a Pneumocystis carinii pneumonia study. We contrast the
      methods with a hypothetical example.

PMID- 14969499
TI  - A bivariate frailty model with a cure fraction for modeling familial correlations
      in diseases.
AB  - We suggest a cure-mixture model to analyze bivariate time-to-event data, as
      motivated by the article of Chatterjee and Shih (2001, Biometrics 57, 779-786),
      but with a simpler estimation procedure and the correlated gamma-frailty model
      instead of the shared gamma-frailty model. This approach allows us to deal with
      left-truncated and right-censored lifetime data, and accounts for heterogeneity,
      as well as for an insusceptible (cure) fraction in the study population. We
      perform a simulation study to evaluate the properties of the estimates in the
      proposed model and apply it to breast cancer incidence data for 5857 Swedish
      female monozygotic and dizygotic twin pairs from the so-called old cohort of the
      Swedish Twin Registry. This model is used to estimate the size of the susceptible
      fraction and the correlation between the frailties of the twin partners. Possible
      extensions, advantages, and limitations of the proposed method are discussed.

PMID- 14969500
TI  - Biological and statistical issues in fitting growth curves to capture-recapture
      data.

PMID- 14969501
TI  - The Quebec Overfeeding Study: a catalyst for new hypothesis generation.

PMID- 14969502
TI  - Role of candidate genes in the responses to long-term overfeeding: review of
      findings.
AB  - An overfeeding experiment conducted with 12 pairs of young male identical twins
      revealed that genetic factors were likely to play an important role in the
      response to caloric affluence. Significant intrapair resemblance was observed for
      the overfeeding-induced changes in body weight, fat mass, abdominal fat, fasting
      insulin, fasting cholesterol and triglycerides. In an attempt to define the
      molecular basis of these genotype-energy balance interaction effects, a panel of
      candidate genes has been investigated. Among the most significant findings, an
      adipsin polymorphism was associated with increases in body weight, total fat mass
      and subcutaneous fat in response to overfeeding. In addition, the beta2
      adrenergic receptor gene Gln27Glu polymorphism showed a strong association with
      the gains in body weight and subcutaneous fat. Only a few markers were related to
      abdominal fat changes and, among them, the adipsin Hinc II polymorphism was
      associated with both computed tomography (CT)-measured abdominal visceral and
      total fat. The changes in insulin parameters brought about by long-term
      overfeeding were influenced most consistently by leptin receptor (LEPR) Gln223Arg
      and insulin-like growth factor-II Apa I polymorphisms. The LEPR Gln223Arg variant
      was also associated with the changes in plasma total triglycerides and high
      density lipoprotein cholesterol concentrations. Further research with larger
      sample sizes should make it possible to identify the specific contributions of
      DNA sequence variations at multiple candidate gene loci in the complex response
      to chronic positive energy balance.

PMID- 14969503
TI  - Caloric restriction, body fat and ageing in experimental models.
AB  - Caloric restriction in animal models delays many age-related pathological
      conditions. Ageing rats have characteristically increased body weight, fat mass
      and a specific body fat distribution. This report will focus on the potential
      cause-effect relationship between increased fat mass and accelerated ageing. In
      humans, increased fat mass (obesity), and in particular increases in abdominal
      obesity as a result of deposition of visceral fat, are associated with the
      metabolic syndrome of ageing. This syndrome is associated with hyperinsulinaemia,
      dyslipidaemia, type 2 diabetes mellitus, atherosclerosis, hypercoagulability and
      hypertension. Fat tissue, however, plays a major role by secreting multiple
      metabolically active factors, which are potentially responsible for the
      development of insulin resistance. This article will review various experimental
      models (in animals) used to prevent insulin resistance of ageing by decreasing
      fat mass, and in particular, decreasing visceral fat. We suggest that this
      decrease in fat mass and its beneficial repercussions observed in ageing animal
      models may apply also to human ageing and its related pathology.

PMID- 14969504
TI  - Fatty acid composition of fats is an early determinant of childhood obesity: a
      short review and an opinion.
AB  - The importance of dietary fat in human obesity remains a controversial issue as
      the prevalence of overweight and obesity has increased despite no dramatic change
      in the amount of ingested fats over the past few decades. However, qualitative
      changes (i.e. the fatty acid composition of fats) have been largely disregarded.
      In this review, we summarize experimental evidence which supports polyunsaturated
      fatty acids of the omega6 series as being potent promoters of both adipogenesis
      in vitro and adipose tissue development in vivo during the gestation/lactation
      period. This conclusion is also supported by epidemiological data from infant
      studies as well as by the assessment of the fatty acid composition of mature
      breast milk and formula milk. It is proposed that unnoticed changes in fatty acid
      composition of ingested fats over the last decades have been important
      determinants in the increasing prevalence of childhood overweight and obesity.

PMID- 14969505
TI  - Hepatic steatosis in obese patients: clinical aspects and prognostic
      significance.
AB  - Non-alcoholic fatty liver disease is a new clinicopathological condition of
      emerging importance, now recognized as the most common cause of abnormal liver
      tests. It is characterized by a wide spectrum of liver damage: simple steatosis
      may progress to advanced fibrosis and to cryptogenic cirrhosis through
      steatohepatitis, and ultimately to hepatocellular carcinoma. Obesity is the most
      significant single risk factor for the development of fatty liver, both in
      children and in adults; obesity is also predictive of the presence of fibrosis,
      potentially progressing to advanced liver disease. From a pathogenic point of
      view, insulin resistance plays a central role in the accumulation of
      triglycerides within the hepatocytes and in the initiation of the inflammatory
      cascade. Chronic hepatocellular injury, necroinflammation, stellate cell
      activation, progressive fibrosis and ultimately, cirrhosis may be initiated by
      peroxidation of hepatic lipids and injury-related cytokine release. In the last
      few years, several pilot studies have shown that treatment with insulin
      sensitizing agents, anti-oxidants or cytoprotective drugs may be useful, but
      there is no evidence-based support from randomized clinical trials. Modifications
      in lifestyle (e.g. diet and exercise) to reduce obesity remain the mainstay of
      prevention and treatment of a disease, which puts a large number of individuals
      at risk of advanced liver disease in the near future.

PMID- 14969506
TI  - Effects of weight loss in overweight/obese individuals and long-term lipid
      outcomes--a systematic review.
AB  - This paper aims to review the evidence for long-term effectiveness of weight loss
      on cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and
      triglycerides in overweight/obese people. Current evidence is mostly based on
      short-term studies. A systematic review of long-term lipid outcomes of weight
      loss in studies published between 1966 and 2001, was conducted. Inclusion
      criteria included all cohort studies and trials carried out on participants with
      body mass index of greater than or equal to 28 kg m(-2). Studies had at least two
      weight change measurements and follow-up of more than 2 years. Thirteen long-term
      studies with a follow-up of more than 2 years were included. Cholesterol has a
      significant positive linear relationship with weight change (r = 0.89) where
      change in weight explains about 80% of the cholesterol difference variation (Adj
      R2 = 0.80). For every 10 kg weight loss a drop of 0.23 mmol L(-1) in cholesterol
      may be expected for a person suffering from obesity or are grossly overweight.
      Weight loss has long-term beneficial effects especially on LDL and cholesterol.
      Weight loss in obese patients should be encouraged and sustained.

PMID- 14969507
TI  - A systematic review of the clinical effectiveness of orlistat used for the
      management of obesity.
AB  - The aim of this paper is to assess the clinical effectiveness of orlistat used
      for the management of obesity. Nineteen electronic databases were searched for
      randomized controlled trials evaluating the effectiveness of orlistat for weight
      loss or maintenance of weight loss in overweight or obese patients. Each included
      trial was assessed for methodological quality. Statistical pooling was performed
      when trials were considered to be sufficiently similar. Twenty-three trials were
      eligible for inclusion. Placebo-controlled trials recruiting patients with
      uncomplicated obesity reported statistically significant differences in favour of
      orlistat for weight loss and changes in obesity-related risk factors at all time
      points. Trials in obese patients with defined risk factors at baseline showed
      similar results, however, smaller effect sizes were observed in patients with
      type 2 diabetes. The effectiveness of orlistat relative to other anti-obesity
      drugs is currently unclear. When orlistat was added to simvastatin, this proved
      to be more effective for weight loss than either drug used individually. Orlistat
      use is associated with a higher incidence of gastrointestinal adverse events
      compared with placebo. In conclusion, orlistat is more effective than placebo in
      promoting weight loss, maintenance of weight loss, and improving cardiovascular
      risk factor profiles. Baseline parameters of patients seen in clinical practice
      should be taken into account when considering treatment.

PMID- 14969508
TI  - Current status of bariatric surgery in the treatment of type 2 diabetes.
AB  - Bariatric surgery (from the Greek words baros meaning 'weight' and iatrikos 'the
      art of healing') is a rapidly evolving branch of surgical science. The aim is to
      induce major weight loss in those whose obesity places them at high risk of
      serious health problems. In an attempt to balance the risks of surgery against
      the benefits of weight loss, bariatric operations are currently performed only in
      the morbidly obese, or those with a body mass index (BMI) > 35 kgm(-2) who
      already have developed comorbidity such as type 2 diabetes. Although weight loss
      is beneficial for obese patients with diabetes, current medical treatment for
      obesity is difficult. In contrast, observational studies show a major impact of
      bariatric surgery on diabetes, raising the question whether this approach should
      be used more widely to treat diabetes in obese patients? If bariatric surgery
      were shown to be the best way to treat diabetes in obese subjects the
      implications for health services would be wide-ranging. Bariatric surgery leads
      to withdrawal of diabetic treatment in about 60% or more of patients, and
      reductions of therapy for many others. Although data on bariatric surgery in
      subjects with diabetes are provocative, most studies have been uncontrolled or
      flawed in other ways. Most importantly, bariatric surgery has not yet been
      compared against standard medical treatment for diabetes in randomized controlled
      trials with diabetes-specific endpoints in all relevant patient groups. Potential
      indications for bariatric surgery are discussed, and the unanswered questions
      that need to be addressed by clinical trials are summarized. Although small
      numbers of patients may be interested in bariatric surgery for type 2 diabetes,
      current data are insufficient to endorse its wide scale use for this indication.
      Until essential studies are undertaken the role and economics of bariatric
      surgery in the diabetic clinic will remain uncertain.

PMID- 14969509
TI  - Increasing the impact of European obesity research in preparation for the
      European research area: a report on the 2003 European Commission Obesity
      Workshop.
AB  - Leading obesity researchers from across Europe assembled in Aberdeen, Scotland,
      in January 2003 to consider how to increase the impact of European obesity
      research. The workshop was funded by the European Commission and hosted by the
      Rowett Research Institute, Aberdeen. The delegates identified the need to (i)
      develop a portfolio of studies that integrate genetics and mechanisms through
      parallel study of humans and animal models and (ii) establish major intervention
      studies in weight management and early life nutrition. It was recommended that
      these goals would be best achieved under the umbrella of a virtual European
      Obesity Research Institute, or Network of Excellence in Obesity Research under
      Framework Programme 6, that would facilitate harmonization of methodology, manage
      centralized standardized resources, coordinate training initiatives, workshops
      and working groups, and increase focus.

PMID- 14969510
TI  - Immunochemical detection of formylated gamma(2)-casein in cheese.
AB  - An immunochemical approach has been developed to detect the use of formaldehyde
      as a bacteriostatic agent in dairy products. A synthetic peptide, reproducing the
      first five amino acid residues of the gamma(2)-casein sequence, was formylated to
      generate the novel haptenic structure, already well-recognized in formaldehyde
      treated milk and arising out of molecular rearrangement after the addition of
      formaldehyde to the alpha-amino group of the histidine residue at the N terminus
      of gamma(2)-casein. A polyclonal antibodies preparation produced against the
      formylated peptide adduct proved to be a highly specific analytical tool for
      detecting the formylated adduct of gamma(2)-casein in formaldehyde-treated milk.
      Polyclonal antibodies obtained against the unmodified peptide were able to detect
      selectively residual native gamma(2)-casein in ripened cheese.

PMID- 14969511
TI  - Fast determination of Sudan I by HPLC/APCI-MS in hot chilli, spices, and oven
      baked foods.
AB  - The Commission Decision of EC dated 20 June 2003, on emergency measures
      concerning hot chilli and hot chilli products coming into any EC member state,
      required that the consignments of such products should be accompanied by an
      analytical report showing that they are free of artificial dye Sudan I. The
      opportunity to set a confirmatory method is evident, and the paper proposes a
      HPLC/APCI-MS method useful for identification and quantitation of Sudan I, also
      at very low levels in hot chilli, other spices, and oven-baked foods. Validation
      data are reported.

PMID- 14969512
TI  - Quantification of beta casein in milk and cheese using an optical immunosensor.
AB  - beta-Casein was quantified in milk and cheese, using an optical immunosensor,
      based on surface plasmon resonance (SPR) measurement. The assay consists of a two
      step sandwich strategy, with two anti-beta-casein antibodies directed against
      each extremity of the casein. This strategy permits only native beta-casein to be
      quantified and not its degradation products. The calibration curve was obtained
      with a reference milk powder of known beta-casein concentration. The analysis
      time per sample was less than 10 minutes. The antibody-coated surface could be
      used for more than 250 determinations. The detection limit was established at 85
      ng x mL(-)(1) and the intra- and inter-assay variation coefficients were 2.6 and
      6.2% respectively. The method was applied to raw milk to quantify intact beta
      casein, with no pretreatment of the sample. A second application was realized
      with cheese, to follow the proteolysis of beta-casein during ripening.

PMID- 14969513
TI  - A simple and rapid assay for analyzing residues of carbamate insecticides in
      vegetables and fruits: hot water extraction followed by liquid chromatography
      mass spectrometry.
AB  - A simple, specific, and rapid analytical method for determining seven largely
      used carbamate insecticides in tomato, spinach, lettuce, zucchini, pear, and
      apple is here presented. This method is based on the matrix solid-phase
      dispersion technique, with heated water as extractant followed by liquid
      chromatography (LC)-mass spectrometry (MS) equipped with a single quadrupole and
      an electrospray ion source. Target compounds were extracted from the vegetal
      matrixes by water heated at 50 degrees C. After acidification and filtration,
      0.25 mL of any aqueous extract was injected in the LC column. MS data acquisition
      was performed in the selected ion monitoring mode, selecting three ions for each
      target compound. Heated water appeared to be an excellent extractant because
      recovery data ranged between 76 (carbaryl in spinach) and 99% (pirimicarb in
      spinach), with RSDs not larger than 10%. Using trimethacarb (an obsolete
      carbamate insecticide) as a surrogate internal standard, the accuracy of the
      analysis varied between 84 and 110%, with RSDs not larger than 9%. On the basis
      of a signal-to-noise ratio of 10, limits of quantification were estimated to
      range between 2 (pirimicarb) and 10 ppb (oxamyl) and were not influenced by the
      type of matrix. When trying to fractionate analytes by using a short
      chromatographic run time, marked weakening of the ion signals for oxamyl,
      methomyl, and aldicarb were observed. This effect was traced to polar endogenous
      co-extractives eluted in the first part of the chromatographic run that
      interfered with gas-phase ion formation for carbamates. Adopting more selective
      chromatographic conditions eliminated this effect.

PMID- 14969514
TI  - Analysis of methoxyfenozide residues in fruits, vegetables, and mint by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS).
AB  - Methoxyfenozide [3-methoxy-2-methylbenzoic acid 2-(3,5-dimethylbenzoyl)-2-(1,1
      dimethylethyl) hydrazide; RH-2485], in the formulation of INTREPID, was applied
      to various crops. Analysis of methoxyfenozide was accomplished by utilizing
      liquid-liquid extraction and partitioning, followed by liquid chromatography
      tandem mass spectrometry (LC-MS/MS). Method validations for fruits, vegetables,
      and mint are reported. Methoxyfenozide mean recoveries ranged from 72 to 129%
      over three levels of fortification. The overall average of mean recoveries is 97
      +/- 10%. The limit of quantitation for fruits, artichoke, cucumber, squash, and
      refined sugar was 0.010 ppm, with a detection limit of 0.005 ppm. For all other
      crops, the limit of quantitation was 0.050 ppm, with a detection limit of 0.025
      ppm. No residues were found greater than the limit of quantitation in control
      samples. Residues above the limit of quantitation were found in all matrices
      except refined sugar. Foliage (bean, beet, pea, and radish) had greater residue
      levels of methoxyfenozide residue than their corresponding roots or pods. Other
      crop matrices contained <1.0 ppm of methoxyfenozide except artichoke, which had a
      mean of 1.10 ppm.

PMID- 14969515
TI  - Determination of the heat treatment undergone by milk by following the
      denaturation of alpha-lactalbumin with a biosensor.
AB  - Dairy industries are interested in knowing the heat treatment undergone by milk
      so as to control the quality of drinking milks or to control their heating
      systems. Among the different techniques available to characterize the heat
      treatment of milk, estimation of the denaturation of proteins has been widely
      used. However, because the concentration of the proteins in raw milk can
      fluctuate significantly, determining only the concentration of a native protein
      without knowing its concentration in the raw milk before undergoing heat
      treatment can lead to significant imprecision. The objective of this study was to
      develop, on Biacore 3000, a biosensor assay for determining the denaturation
      index of alpha-lactalbumin by quantifying separately the native and "heat
      denatured" forms of alpha-lactalbumin with specific monoclonal antibodies. alpha
      Lactalbumin denaturation index is independent of the concentration of alpha
      lactalbumin in the original raw milk. The technique developed is discriminating,
      fast, repeatable, fully automated, and requires no pretreatment of the milk
      sample.

PMID- 14969516
TI  - Quantitative determination of allicin in garlic: supercritical fluid extraction
      and standard addition of alliin.
AB  - A quantitative method is described for the determination of allicin (2-propene-1
      sulfinothioic acid S-2-propenyl ester) in garlic, using standard additions of
      alliin (l-(+)-S-allylcysteine sulfoxide) in conjunction with supercritical fluid
      extraction (SFE) and high performance liquid chromatography analysis with UV-vis
      absorbance detection. Optimum CO(2)-SFE conditions provided 96% recovery for
      allicin with precision of 3% (RSD) for repeat samples. The incorporation of an
      internal standard (allyl phenyl sulfone) in the SFE step resulted in a modest
      improvement in recovery (99%) and precision (2% RSD). Standard additions of
      alliin were converted to allicin in situ by endogenous alliinase (l-(+)-S
      alk(en)ylcysteine sulfoxide lyase, EC 4.4.1.4). Complete conversion of the spiked
      alliin to allicin was achieved by making additions after homogenization-induced
      conversion of the naturally occurring cysteine sulfoxides to thiosulfinates had
      taken place, thus eliminating the likelihood of competing reactions.
      Concentration values for allicin determined in samples of fresh garlic (Allium
      sativum L. and Allium ampeloprasum) and commercially available garlic powders
      (Allium sativum L.) by standard addition of alliin were found in all cases to be
      in statistical agreement (95% confidence interval) with values determined using a
      secondary allicin standard (concentration determined using published extinction
      coefficients). This method provides a convenient alternative for assessing the
      amount of allicin present in fresh and powdered garlic, as alliin is a far more
      stable and commercially prevalent compound than allicin and is thus more amenable
      for use as a standard for routine analysis.

PMID- 14969517
TI  - Comparison of HPLC methods for determination of anthocyanins and anthocyanidins
      in bilberry extracts.
AB  - An HPLC method and an acid hydrolysis HPLC method for the analysis of
      anthocyanins and anthocyanidins in bilberry extracts have been developed. The
      HPLC method coupled with a mass detector has identified 11 anthocyanins in
      bilberry extracts. The method provides anthocyanin profiles that are very useful
      in verifying the identity of botanical raw materials, monitoring the consistency
      of the raw material source, and quantitating the total anthocyanins. The acid
      hydrolysis HPLC method greatly simplifies the anthocyanin profile in bilberry
      samples and converts anthocyanins to five major anthocyanidin aglycones:
      delphinidin, cyanidin, petunidin, peonidin, and malvidin. Each of these aglycones
      can be separated completely and quantitated accurately with external standards.
      Various extraction and hydrolysis conditions were investigated, and the
      advantages and disadvantages of the HPLC and acid hydrolysis methods are
      discussed.

PMID- 14969518
TI  - Metabolite profiling using (1)H NMR spectroscopy for quality assessment of green
      tea, Camellia sinensis (L.).
AB  - A set of 191 green teas from different countries was collected and analyzed by
      (1)H NMR. It was proposed to establish if the teas could be discriminated
      according to the country of origin or with respect to quality. Both principal
      component analysis (PCA) and cluster analysis were applied to the data. Some
      separation of Chinese and non-Chinese teas was observed. The present results did
      not allow allocation of samples to individual countries, but cluster analysis
      suggested that it might be possible with an augmented sample set. The PCA did
      show a separation between the Longjing type (highest quality Chinese tea) and
      most other Chinese teas and indicated some metabolites that could be responsible
      for the difference. Longjing teas showed higher levels of theanine, gallic acid,
      caffeine, epigallocatechin gallate, and epicatechin gallate and lower levels of
      epigallocatechin when compared with other teas. These compounds have been
      mentioned previously in connection with quality, but it was also shown that
      higher levels of theogallin (5-galloyl quinic acid), theobromine, 2-O-(beta-l
      arabinopyranosyl)-myo-inositol and some minor sugar-containing compounds were
      found in Longjing teas while higher levels of fatty acids and sucrose were found
      in the other teas. These new markers could prove to be useful for the
      authentication of bulk tea.

PMID- 14969519
TI  - Amino Acid contents in raw materials can be precisely analyzed in a global
      network of near-infrared spectrometers: collaborative trials prove the positive
      effects of instrument standardization and repeatability files.
AB  - Four international ring trials for NIRS amino acid analysis of feed raw materials
      have demonstrated for the first time that the calibrations developed by Degussa
      allow reliable and precise predictions of essential amino acids in up to 44 NIR
      spectrometers. Different standardization techniques were compared, and the
      effectiveness of using spectra of the host instruments as repeatability files was
      studied. The ultimately achieved reproducibility of 2-3% CV for almost all
      analyses in the network is considerably better than ring trial results for wet
      chemical amino acid analysis.

PMID- 14969520
TI  - Monoclonal antibodies for the analysis of gossypol in cottonseed products.
AB  - Immunogens, prepared by conjugating either (+)-gossypol or (-)-gossypol to
      Limulus polyphemushemolymph protein, were used for immunization in the production
      of monoclonal antibodies. Hybridoma were evaluated for their relative affinity to
      racemic gossypol, (+)-gossypol, (-)-gossypol, gossypol analogues, and their
      lysine derivatives. The monoclonal antibody obtained showed higher affinity to
      gossypol and gossypol analogues as compared to their lysine derivative
      counterparts. An indirect competitive enzyme-linked immunosorbent assay (ELISA)
      with this antibody was used to measure gossypol in 15 cottonseed meal products;
      the results showed good correlation with results obtained using the AOCS (free
      gossypol) official method (R(2) = 0.89). The direct recognition of both free
      gossypol and bound gossypol using this antibody will be useful for rapid
      screening and quality control.

PMID- 14969521
TI  - Fractionation of grape anthocyanin classes using multilayer coil countercurrent
      chromatography with step gradient elution.
AB  - Grape anthocyanins from rose wine pomace and grape skins were fractionated by
      multilayer coil countercurrent chromatography (MLCCC). Tert-butyl methyl ether/n
      butanol/acetonitrile/water acidified with trifluoroacetic acid (2/2/x/5) was
      chosen as the solvent system because of its demonstrated efficiency in separating
      anthocyanins. A method combining MLCCC and step gradient elution has been
      developed. This method enabled the fractionation of anthocyanins as series of
      glucosides, and the corresponding acetylated, coumaroylated, and caffeoylated
      derivatives. The different anthocyanins were identified on the basis of their UV
      spectra, their elution time on reversed-phase HPLC as well as by mass
      spectrometry. A polar-colored fraction free of anthocyanin monomers and
      corresponding to the material remaining in the stationary phase after the
      completion of the gradient was recovered.

PMID- 14969522
TI  - Solution-state nuclear magnetic resonance study of the similarities between
      milled wood lignin and cellulolytic enzyme lignin.
AB  - The structures of milled wood lignin (MWL) and cellulolytic enzyme lignin (CEL)
      have been analyzed using traditional chemical methods and solution-state NMR
      techniques. Comparisons of the results obtained reveal that subtle differences
      exist between the two lignin preparations. Thioacidolysis produced higher monomer
      yields from CEL than MWL, suggesting MWL has a more condensed structure.
      Quantitative (13)C NMR determined the degree of condensation in MWL to be 0.43
      unit per aromatic moiety as compared to 0.36 in CEL. The MWL also contained a
      lower amount of beta-O-4' substructures per aromatic ring than CEL, 0.41 versus
      0.47, respectively. Carbohydrate analysis revealed that the MWL may contain a
      higher proportion of middle lamella material as compared to the CEL. Because the
      middle lamella is considered to have a more condensed lignin structure, on the
      basis of the bulk polymerization theory, these results could explain the
      differences in beta-O-4' and degree of condensation.

PMID- 14969523
TI  - Determination of carbamate pesticide residues in vegetables and fruits by liquid
      chromatography-atmospheric pressure photoionization-mass spectrometry and
      atmospheric pressure chemical ionization-mass spectrometry.
AB  - A liquid chromatography-atmospheric pressure photoionization (APPI)-mass
      spectrometry method was developed for the determination of 22 carbamates
      including their metabolites in vegetables and fruits. For the optimization of
      APPI, several APPI ion source parameters were examined. As a result, many
      carbamates with APPI using the optimized parameter gave simple mass spectra, and
      a strong signal corresponding to [M + H](+) was observed except for aldicarb.
      However, some carbamate metabolites gave ammonium adduct ions [M + NH(4)](+) as
      base peak ions. The mean recovery of each carbamate from grape and onion samples
      spiked at 5 ng/g was 81.7-105.7%, with relative standard deviations of 3.3-5.9%.
      Furthermore, matrix constituents did not significantly influence the ionization
      efficiency. The limit of detection (S/N = 3) in grape and onion was in the range
      of 0.33-3.33 ng/g. For the robustness of this method, this system has been used
      to analyze 50 samples, and the intensities for all carbamates were found to be
      unaffected by the contamination of the APPI source by sample matrix constituents.
      This result indicates that the method is reliable.

PMID- 14969524
TI  - Determination of enantiomers of synthetic pyrethroids in water by solid phase
      microextraction - enantioselective gas chromatography.
AB  - Solid phase microextraction (SPME) is an ideal sample preparation technique
      because of its speed and solvent-free features. Sampling by SPME is selective and
      only the dissolved concentration is measured, which allows measurement of the
      bioavailable fraction of a contaminant in aqueous media. One potential
      application of SPME is for analysis of enantiomers of chiral contaminants in
      environmental samples. In this study, a method was developed for determining
      enantiomers of (Z)-cis-bifenthrin and cis-permethrin in water using coupled SPME
      and enantioselective gas chromatography (GC). Following SPME sampling,
      enantiomers of (Z)-cis-bifenthrin and cis-permethrin were separated at the
      baseline on a beta-cyclodextrin-based enantioselective column, and analyte
      enrichment onto the SPME fiber was not enantioselective. The GC response
      increased as sampling time was increased from 0 to 240 min, and as sampling
      temperature was increased from 20 to 40 degrees C. Organic solvents such as
      methanol, acetone, and acetonitrile enhanced, while soil extracts slightly
      decreased, the GC response. The integrated SPME-enantioselective GC method was
      used to analyze surface runoff samples. The analysis showed preferential
      degradation of the 1S-3S enantiomer over the 1R-3R enantiomer for both (Z)-cis
      bifenthrin and cis-permethrin. The concentrations detected by SPME-GC were
      substantially smaller than those determined following solvent extraction,
      suggesting that SPME-enantioselective GC analysis selectively measured the
      dissolved fraction.

PMID- 14969525
TI  - New method for evaluating astringency in red wine.
AB  - Astringency is an important sensory attribute of red wine. It is usually
      estimated by tasting and is subject to a certain subjectivity. It can also be
      estimated by using the gelatin index. This procedure is not very reproducible
      because there are many gelatins on the market with a heterogeneous composition.
      Furthermore, the gelatin index determines procyanidin concentration by acid
      hydrolysis that gives only an approximate result. This paper proposes a new and
      reproducible method that determines astringency by using ovalbumin as the
      precipitation agent and tannic acid solutions as standards. Statistical analysis
      of the results indicates that this method is more reproducible (RSD = 5%) than
      the gelatin index (RSD = 12%) and correlates better with sensorial analysis.

PMID- 14969526
TI  - Assessing N,N'-Dibutylurea (DBU) formation in soils after application of n
      butylisocyanate and benlate fungicides.
AB  - N,N'-Dibutylurea (DBU) is a breakdown product of benomyl [methyl 1
      (butylcarbamoyl)-2-benzimidazole carbamate], the active ingredient in Benlate
      fungicides, and has been proposed as one cause for crop damage that growers claim
      to have occurred from the use of Benlate 50 DF fungicide. This study assessed DBU
      formation upon (1). application of n-butyl-1-[(14)C]butylisocyanate (BIC), the
      immediate precursor to DBU formation, in four soils at two water potentials (0.03
      and 0.1 MPa) and (2). application of benomyl butyl-1-(14)C-benomyl enriched
      Benlate DF and SP fungicides to two soils at various combinations of negative
      water potential (0.03 or 0.1 MPa) and temperature (23 or 33 degrees C). Parent
      compounds, metabolites, and (14)CO(2) were tracked using chromatographic analysis
      with radioassay and UV detection, liquid scintillation counting, and
      postextraction oxidation of the soil. At 0.03 MPa in all four BIC-treated soils,
      DBU formation was never detected. At 0.1 MPa, DBU was detected in two soils, but
      at concentrations <3.6 microg kg(-)(1) (0.3 wt % of applied BIC). In both soils
      treated with benomyl formulations, DBU formation was observed with only Benlate
      50 DF application at 0.03 MPa and 23 degrees C, which was followed by rapid
      dissipation of DBU. The maximum concentration observed was 0.41 microg g(-)(1)
      (0.65 wt % of applied benomyl at 62.8 microg g(-)(1)), which is well below levels
      currently reported to cause adverse effects to plants. Combined benomyl and
      carbendazim half-lives in soils across treatments were 2-3 months. This study
      demonstrated that further production and accumulation of DBU in soils after
      Benlate application or from residual benomyl remaining in the soil are highly
      unlikely and that persistence of any DBU in soils is likely to be short-lived.

PMID- 14969527
TI  - Separation and analysis of diastereomers and enantiomers of cypermethrin and
      cyfluthrin by gas chromatography.
AB  - Synthetic pyrethroid (SP) insecticides are of environmental significance because
      of their high aquatic toxicity. Due to their chirality, SP compounds contain
      multiple diastereomers and enantiomers. However, due to great structural
      similarities and lack of isomer standards, gas chromatographic (GC) analysis of
      SP diastereomers or enantiomers is poorly developed. In this study, we used a HP
      5 column to separate the diastereomers and a beta-cyclodextrin-based
      enantioselective column (BGB-172) to separate the enantiomers of cypermethrin
      (CP) and cyfluthrin (CF). Resolved peaks were identified by comparing
      chromatograms of isomer-enriched CP products. Diastereomers of both CP and CF
      were separated on the HP-5 column. On the BGB-172 column, enantiomers of all cis
      diastereomers were separated, while those of trans diastereomers were not
      separated. The elution order appears to be regulated by configuration, a finding
      which may allow peak identification in the absence of isomer standards. When
      coupled with electron capture detection, the developed methods had low detection
      limits and may be used for analysis of SP diastereomers and enantiomers in
      environmental samples.

PMID- 14969528
TI  - Antioxidant properties of aqueous extracts from selected lamiaceae species grown
      in Turkey.
AB  - Water-soluble extracts from black thyme (Thymbra spicata L.), savory (Satureja
      cuneifolia Ten.), Spanish oregano (Coridothymus capitatus (L.) Reichb. f.), sweet
      marjoram (Majorana hortensis Moench), Syrian oregano (Origanum syriacum L.), Toka
      oregano (Origanum minutiflorum O. Schwarz et P. H. Davis), and Turkish oregano
      (Origanum onites L.) were screened for antioxidant properties in a battery of six
      in vitro assays. Total phenol content and qualitative-quantitative compositional
      analyses were also carried out. The extracts demonstrated varying degrees of
      efficacy in each screen. The savory extract was the most effective at reducing
      iron(III), scavenging 1,1-diphenyl-2-picrylhydrazyl radicals, inhibiting
      ascorbate-iron(III)-catalyzed hydroxyl radical-mediated brain phospholipid
      peroxidation, and site-specific hydroxyl radical-mediated 2-deoxy-d-ribose
      degradation. The Syrian oregano extract was the most effective chelator of
      iron(II), while Spanish and Turkish oregano extracts were the most effective
      inhibitors of nonsite-specific hydroxyl radical-mediated 2-deoxy-d-ribose
      degradation. All the extracts contained Folin-Ciocalteu reagent-reactive
      substances, which was confirmed by the presence of polar phenolic analytes (i.e.,
      hydroxybenzoates, hydroxycinnamates, and flavonoids).

PMID- 14969529
TI  - Inhibitory profile of nonapeptide derived from porcine troponin C against
      angiotensin I-converting enzyme.
AB  - A novel angiotensin I-converting enzyme (ACE) inhibitory peptide (RMLGQTPTK;
      9mer) from porcine skeletal troponin C was investigated for its inhibitory
      profile. This peptide was noncompetitive and as hydrophobic as the known ACE
      inhibitory peptides. Aminopeptidase M quickly hydrolyzed 9mer, resulting in
      production of MLGQTPTK and LGQTPTK with inhibitory activities similar to those of
      9mer. The main hydrolysis product of 9mer with carboxypeptidase A and B was
      RMLGQTPT showing very weak activity. Most products derived from 9mer hydrolysis
      by ACE, aminopeptidase, or carboxypeptidase showed weak but definite ACE
      inhibitory activities. Thus, 9mer was estimated to be a wholly efficient
      inhibitor with these fragment peptides.

PMID- 14969530
TI  - Antifungal activity of beta-asarone from rhizomes of Acorus gramineus.
AB  - An antifungal substance was isolated from the extract of Acorus gramineus using
      various chromatographic procedures. The antibiotic was identified as beta
      asarone, cis-2,4,5-trimethoxy-1-propenylbenzene, on the basis of the high
      resolution EI-mass, NMR, and UV spectral data. Beta-asarone completely inhibited
      mycelial growth of some plant pathogenic fungi, Cladosporium
      cucumerinum,Colletotrichum orbiculare, Magnaporthe grisea, and Pythium ultimum,
      in a range of 0.5-30 microg/mL. The growth of Bacillus subtilis, Erwinia
      carotovora subsp. carotovora, Ralstonia solanacearum, and Xanthomonas campestris
      pv. vesicatoria was slightly suppressed by beta-asarone. As the concentration of
      beta-asarone increased, M. grisea infection was drastically inhibited on rice
      leaves. Treatment with 500 microg/mL of beta-asarone also greatly suppressed
      lesion formation of Co. orbiculare on cucumber leaves. This is the first study to
      demonstrate in vitro and in vivo antifungal activity of beta-asarone against
      plant fungal pathogens M. grisea and C. orbiculare.

PMID- 14969531
TI  - Volatile constituents from the leaves of Callicarpa japonica Thunb. and their
      antibacterial activities.
AB  - Volatile substances of Callicarpa japonica Thunb. were examined for their
      antibacterial activities against six foodborne microorganisms using the optical
      densitometer Bioscreen C. Extracts of C. japonica were obtained by simultaneous
      steam distillation and solvent extraction (SDE), and those extracted for 1.5 and
      2.0 h at pH 6.0 strongly inhibited the growth of Bacillus cereus and Salmonella
      typhimurium; the content of the volatile substances of leaves at these pH levels
      were 543.1 and 706.7 mg/kg, respectively. All foodborne microorganisms tested
      were strongly inhibited by the addition of >8% (v/v) of the SDE extracts to broth
      medium. The major volatile components of the SDE extracts obtained at 1.5 h and
      pH 6.0 were gamma-caryophyllene, 1-octen-3-ol, 2-hexenal, germacrene B, and
      aromadendrene II, with corresponding peak areas of 44.14, 15.6, 9.86, 5.24, and
      4.01%, respectively, and major antibacterial components were 1-octen-3-ol and 2
      hexenal. Among the 32 materials identified as volatile flavor components, 2
      hexenal, 2,4-hexadienal, 1-octen-3-ol, 2,4-heptadienal, and epiglobulol strongly
      inhibited microorganism growth. In particular, 2-hexenal (107.52 mg/L) and 1
      octen-3-ol (678.64 mg/L) inhibited the growth of most microorganisms tested by
      >90%.

PMID- 14969532
TI  - Enzymatic grafting of peptides from casein hydrolysate to chitosan. Potential for
      value-added byproducts from food-processing wastes.
AB  - Tyrosinase was used to initiate the grafting of peptides onto the amine
      containing polysaccharide chitosan. Chemical evidence for covalent grafting was
      obtained from electrospray mass spectrometry for products formed from reactions
      with glucosamine (the monomeric unit of chitosan) and the model dipeptide Tyr
      Ala. When this model dipeptide was incubated with tyrosinase and chitosan, there
      was a marked increase in the viscosity of the solution. This viscosity increase
      provides physical evidence that tyrosinase can initiate peptide grafting onto the
      chitosan backbone. A peptide-modified chitosan derivative was generated by
      reacting chitosan (0.32 w/v%) with acid-hydrolyzed casein (0.5 w/v %) using
      tyrosinase. After reaction, the peptide-modified chitosan was partially purified
      and dissolved in an aqueous acetic acid solution. Low concentrations of this
      peptide-modified chitosan were observed to confer viscoelastic properties to the
      solutions. Specifically they conferred high viscosities and shear thinning
      properties to the solutions, and solutions containing only 1 w/w % of the peptide
      modified chitosan behaved as weak gels. Thus, tyrosinase provides a simple and
      safe way to convert food-processing byproducts into environmentally friendly
      products that offer useful functional properties. The selectivity of tyrosinase
      and the relatively high reactivity of chitosan's amines allow grafting to be
      performed with uncharacterized peptide mixtures present in crude hydrolysates.

PMID- 14969533
TI  - Identification of a genomic clone to ACC oxidase from papaya (Carica papaya L.)
      and expression studies.
AB  - In this paper are presented structural analysis and expression studies of one
      genomic clone encoding a 1-aminocyclopropane-1-carboxylate oxidase (ACC oxidase)
      from papaya. Using RT-PCR amplification of ACC oxidase cDNAs from ripe papaya, a
      product of 800 bp was obtained, which after sequence analysis was found to code
      for a protein highly homologous to ACC oxidase proteins. This PCR product was
      used as a probe for screening a genomic library, and two different groups of
      clones were obtained as indicated by restriction mapping. One clone (CPACCO-1)
      was selected for further study and fully sequenced. Comparison of this sequence
      with the PCR product and other cloned ACC oxidase genes revealed that CPACCO-1
      encoded the transcript in four exons interrupted by three introns. Southern blot
      analysis showed one or two major bands hybridized to the PCR probe, suggesting
      that the ACC oxidase gene is present in one or two copies in the papaya genome.
      By northern blot analysis it was found that the ACC oxidase transcripts appear in
      the pulp earlier than in the peel, suggesting a developmental regulation. A
      wounding experiment revealed the highest expression of this gene by 2 h.
      Transcriptional regulation by ethylene could be due to the presence of a putative
      GCC box in the promoter region.

PMID- 14969534
TI  - Formulation of low-cost fermentative media for lactic acid production with
      Lactobacillus rhamnosus using vinification lees as nutrients.
AB  - Lees coming from different steps in white wine and red wine vinification were
      characterized under physicochemical analyses to determine the content in carbon,
      nitrogen, ashes, solids in suspension, organic compounds, and minerals. Due to
      the hydrolytic activity of Lactobacillus strains, lees without autolysis
      treatments were used directly as the unique nutrient or in combination with corn
      steep liquor to carry out the glucose to lactic acid fermentation with
      Lactobacillus rhamnosus CECT-288. Time courses of glucose and lactic acid were
      modeled according to reported models. Using 20 g/L of lees coming from the white
      wine technology and re-collected after the second decanting step before
      distillation, as the only nutrient, the values achieved (P = 105.5 g/L, Q(P) =
      2.470 g/L.h) were even higher than those obtained with the costly MRS broth (P =
      104.3 g/L, Q(P) = 2.251 g/L.h).

PMID- 14969535
TI  - Method for the detection of synthetic cry3A in transgenic potatoes.
AB  - All transgenic cultivars of potatoes registered in Canada and the United States
      have been modified to express a synthetic cry3A gene as a means of conferring
      resistance against the Colorado potato beetle, an important economic pest of
      potatoes. A PCR method was developed to amplify a 499 bp region of the synthetic
      cry3A gene. Using this method, synthetic cry3A could be detected in six different
      transgenic cultivars. Positive results could be confirmed with PvuII restriction
      digestion of the PCR-generated amplicon, which resulted in two fragments that
      were 283 and 216 bp in size. Of the 52 tuber extracts tested with this method, no
      false positive or false negative results were obtained, suggesting the method
      could be used with a high degree of accuracy. The absolute limit of detection was
      the number of cry3A copies present in one or perhaps two haploid copies of the
      potato genome. The practical limit of detection in tubers on a fresh weight basis
      was 0.02% for the NL 10-SUP and 0.01% for the remaining cultivars. Synthetic
      cry3A could also be detected in processed food products such as potato chips,
      shoestring potatoes, and frozen French fries. The method was suitable for
      screening potato tuber lots and some processed foods for the presence of
      synthetic cry3A.

PMID- 14969536
TI  - Abiotic degradation of lignified cell walls by carbonate and copper salt.
AB  - This study reports on the destructuration of Wheat straw and Spruce wood cell
      walls after maceration in potassium carbonate or sodium hydroxide at pH = 10 in
      the presence of copper acetate. The alkaline treatments had a predominant impact
      on the wheat straw cell wall components over copper acetate. Either K-carbonate
      or Na-hydroxide extracted from wheat straw a particular lignin fraction rich in
      condensed C-C linkages, leading to the unmasking of new ether-linked sub
      structures in the cell wall. This unmasking was increased in the presence of
      copper salt but only in the nonextracted Wheat straw sample incubated in
      carbonate and not in the corresponding extractive-free sample. This difference
      was related to the leaching of compounds from the nonextracted cell wall, which
      could sustain oxidative activity of copper by hindering its precipitation into
      inactive hydroxide and/or carbonate species. In Spruce wood samples, copper salt
      was the principal factor impacting on the lignin structure over alkali alone. Its
      effect was, however, only detected at the level of C-C linked dimers. These
      results confirmed that unmasking of lignin sub-structures also occurred in Spruce
      wood, but probably through mechanisms different from that evidenced in Wheat
      straw.

PMID- 14969537
TI  - Wheat flour enzymatic amylolysis monitored by in situ (1)H NMR spectroscopy.
AB  - Starch enzymatic degradation caused by endogenous hydrolases is studied by in
      situ NMR spectroscopy on a set of hard and soft wheat flours. The results
      obtained by two different techniques (HR-MAS and (1)H NMR in solution) are
      analyzed in terms of a Michaelis-Menten kinetic phenomenological model taking
      into account the presence of endogenous enzymes and their eventual inactivation.
      The parameters resulting from the best fit of all experimental data to the
      kinetic model equations are submitted to a multivariate statistical analysis to
      assess the role of the oligosaccharides release in distinguishing between hard
      and soft wheats.

PMID- 14969538
TI  - Establishment of selenium uptake and species distribution in lupine, Indian
      mustard, and sunflower plants.
AB  - Selenium has been recognized as essential for all mammals; therefore, its
      concentration level and speciation are of great concern. Plants are one of the
      main sources of selenium in the diet. Thus, inorganic selenium uptake and its
      transformation in different species were evaluated in Indian mustard (Brassica
      juncea), sunflower (Helianthus annus), and white lupine (Lupinus albus). More
      than 1.2 g x kg(-)(1) (dry matter) of Se was found in the aerial part of Indian
      mustard when growing on 1 mg x L(-)(1) of Se as Na(2)SeO(4), and approximately
      half this amount was determined in the leaves of the lupine, which is still quite
      high. Selenomethionine was the main selenium-containing amino acid identified in
      most of the extracts by HPLC-ICP-MS. The higher values were 6.8 and 14.5 mg x kg(
      )(1) (expressed as Se in dry matter) in the leaves of lupine and sunflower,
      respectively. This is of great importance because some authors have considered
      the combination of this enriched material with non-enriched food as a source of
      selenium supplementation.

PMID- 14969539
TI  - Comparative study of crude and purified cellulose from wheat straw.
AB  - A sequential totally chlorine-free procedure for isolation of cellulose from
      wheat straw was proposed in this study. The dewaxed straw was pretreated with 0.5
      M NaOH in 60% methanol at 60 degrees C for 2.5 h under ultrasonic irradiation for
      0-35 min and sequentially posttreated with 2% H(2)O(2)-0.2% TAED at pH 11.8 for
      12 h at 48 degrees C, which together solubilized 85.3-86.1% of the original
      hemicelluloses and 91.7-93.2% of the original lignin, respectively. The yield of
      crude cellulose ranged between 46.2 and 49.2% on a dry weight basis related to
      wheat straw, which contained 11.2-12.2% residual hemicelluloses and 2.5-2.9%
      remaining lignin. Further treatment of the corresponding crude cellulosic
      preparations with 80% acetic acid-70% nitric acid under the condition given
      yielded 36.8-37.7% of the purified cellulose, which contained minor amounts of
      bound hemicelluloses (2.5-2.8%) and was relatively free of associated lignin (0.1
      0.2%). The isolated crude and purified cellulose samples were comparatively
      studied by FT-IR and CP/MAS (13)C NMR spectroscopy, and the relative
      crystallinity was also estimated. The final stage treatment with 80% acetic acid
      70% nitric acid decreased the hemicelluloses and lignin associated in the crude
      cellulose but led to 3.1-5.4% degradation of the original cellulose; in addition,
      the purity of the obtained cellulose was high. However, it was found that the
      final stage treatment is not severe enough to cause decrystallization of
      cellulose. The thermal stability of the purified cellulose is higher than that of
      the corresponding crude cellulose.

PMID- 14969540
TI  - Characterization and quantification of anthocyanins and polyphenolics in
      bluehHoneysuckle (Lonicera caerulea L.).
AB  - Anthocyanins and phenolics of 10 blue honeysuckle (Lonicera caerulea L.)
      genotypes were characterized and quantified by HPLC-DAD. Peak assignments were
      confirmed by low-resolution electrospray mass spectrometry. Six anthocyanins were
      detected with the major peak identified as cyanidin 3-glucoside. Five additional
      anthocyanins were characterized as cyanidin 3,5-diglucoside, cyanidin 3
      rutinoside, pelargonidin 3-glucoside, peonidin 3-glucoside, and peonidin 3
      rutinoside. Four polyphenolics were identified as chlorogenic acid,
      neochlorogenic acid, quercetin 3-rutinoside, and quercetin 3-glucoside. Two
      additional unidentified phenolics were characterized as flavonol and
      hydroxycinnamic derivatives based on UV-vis spectra. Hydroxycinnamate levels
      ranged from 30.4 to 156.2 mg/100 g, whereas the flavonol content ranged from 12.6
      to 32.8 mg/100 g. The L. caerulea subspecies boczkarnikovae contained the highest
      amounts of hydroxycinnamic derivatives and flavonols.

PMID- 14969541
TI  - Carbohydrate composition of selected plum/prune preparations.
AB  - Eighteen plum/prune preparations and byproducts were analyzed for proximate
      constituents and carbohydrate profiles. Plum puree and prune juice contained the
      highest concentrations of ash (13.0 and 13.8%, respectively). Crude protein (CP),
      acid-hydrolyzed fat (AHF), and total dietary fiber (TDF) concentrations were
      higher in byproducts (waste cake and dried plum pits) compared with the other
      fractions. Several classes of oligosaccharides were found in low concentrations
      in many of the substrates and were associated with the fruit rather than the pit.
      Maltooligosaccharides were found in very high concentrations in three of the
      preparations as a result of the addition of maltodextrin during processing.
      Monosaccharides, sugar alcohols, and oligosaccharides were found in higher
      concentrations in the fruit than in the pit and accounted for 2.9-84.7% of
      substrate organic matter. These results indicate that carbohydrates of various
      types constitute a significant proportion of plum/prune preparations and
      byproducts.

PMID- 14969542
TI  - Field-incurred fenitrothion residues in kakis: comparison of individual fruits,
      composite samples, and peeled and cooked fruits.
AB  - Field trials have been carried out to determine the variability of residue levels
      of fenitrothion and its main metabolites fenitrothion-oxon and 3-methyl-4
      nitrophenol in individual kaki fruits versus composite samples, in peel versus
      flesh, and in whole uncooked versus whole cooked fruits. Residue levels have been
      determined by gas chromatography with thermionic specific detection after
      extraction with ethyl acetate and without further cleanup. At harvest, residue
      levels of fenitrothion were below maximum residue levels (MRLs) and the two
      metabolites 3-methyl-4-nitrophenol and fenitrothion-oxon could be quantified with
      average amounts of 0.080 and 0.012 mg/kg, respectively. Levels of fenitrothion
      decreased 88% after peeling, whereas temperature did not result in a high
      variation. The ratios of the highest residue level in the individual fruits to
      the corresponding mean of residue levels in the composite samples for
      fenitrothion were <3. This value is lower than that recommended by the World
      Health Organization as default value for consumer risk assessment.

PMID- 14969543
TI  - Preparation and characterization of inclusion complex of norflurazon and beta
      cyclodextrin to improve herbicide formulations.
AB  - The formulation of inclusion complexes of the herbicide norflurazon as guest and
      beta-cyclodextrin (beta-CD) as host has been studied as a first step in the use
      of cyclodextrins to obtain improved formulations of this herbicide. The
      interaction of norflurazon with beta-CD produced the formation of an inclusion
      complex in solution and in solid state. The inclusion of norflurazon in beta-CD
      in solution was studied by phase solubility, and an apparent stability constant
      of 360 M(-)(1), a 1:1 stoichiometric ratio for the complex, and up to 5-fold
      increase in norflurazon solubility were determined. Three processing methods
      (kneading, spray drying and vacuum evaporation) were used to prepare norflurazon
      beta-CD solid inclusion complexes. X-ray diffraction, infrared spectroscopy,
      differential scanning calorimetry, and scanning electron microscopy techniques
      were used to study the solid complexes. From the different solid systems, an
      increase of norflurazon aqueous dissolution rate was obtained in comparison to
      the uncomplexed herbicide. This finding is a first step to obtain controlled
      release and/or protective formulations of norflurazon, which allow a more
      rational application of norflurazon, diminishing the use of organic solvents and
      increasing its efficacy.

PMID- 14969544
TI  - Aqueous photolysis of niclosamide.
AB  - The photodegradation of [(14)C]niclosamide was studied in sterile, pH 5, 7, and 9
      buffered aqueous solutions under artificial sunlight at 25.0 +/- 1.0 degrees C.
      Photolysis in pH 5 buffer is 4.3 times faster than in pH 9 buffer and 1.5 times
      faster than in pH 7 buffer. In the dark controls, niclosamide degraded only in
      the pH 5 buffer. After 360 h of continuous irradiation in pH 9 buffer, the
      chromatographic pattern of the degradates was the same regardless of which ring
      contained the radiolabel. An HPLC method was developed that confirmed these
      degradates to be carbon dioxide and two- and four-carbon aliphatic acids formed
      by cleavage of both aromatic rings. Carbon dioxide was the major degradate,
      comprising approximately 40% of the initial radioactivity in the 360 h samples
      from both labels. The other degradates formed were oxalic acid, maleic acid,
      glyoxylic acid, and glyoxal. In addition, in the chloronitroaniline-labeled
      irradiated test solution, 2-chloro-4-nitroaniline was observed and identified
      after 48 h of irradiation but was not detected thereafter. No other aromatic
      compounds were isolated or observed in either labeled test system.

PMID- 14969545
TI  - Response of selected horseweed (Conyza canadensis (L.) Cronq.) populations to
      glyphosate.
AB  - Horseweed (Conyza canadensis (L.) Cronq.) seed was collected in Illinois,
      Indiana, Kentucky, Mississippi, Missouri, and Ohio to determine susceptibility of
      different horseweed biotypes to glyphosate. Horseweed resistant to glyphosate was
      found in Mississippi, Ohio, and western Tennessee. In a separate experiment
      examining Tennessee biotypes, a dose response curve demonstrated that four times
      as much glyphosate was needed to achieve a 50% fresh weight reduction (GR(50)) in
      resistant biotypes when compared to a susceptible biotype. Resistant biotypes
      from Tennessee displayed a GR(50) of 1.6 kg/ha as compared to a GR(50) of 0.4
      kg/ha in a susceptible horseweed population. Although growth was reduced, the
      resistant plants did not completely die and could potentially produce seed.
      Variation in glyphosate resistance was found among the populations tested.

PMID- 14969546
TI  - Effect of soil type on adsorption-desorption, mobility, and activity of the
      herbicide norflurazon.
AB  - Adsorption-desorption studies of norflurazon on 17 soils of very different
      characteristics have been performed using a batch equilibration method and
      correlated to its mobility, activity, and persistence in soils. The influence of
      different soil properties and components on norflurazon adsorption was
      determined. The significant variables were organic matter (OM) content and iron
      and aluminum oxides, which accounted for 85 and 11% of the variability,
      respectively. Norflurazon desorption from soils was hysteretic in all cases,
      being more irreversible at the lowest herbicide concentrations adsorbed. The
      percentage of norflurazon eluted from columns of selected soils reached almost
      100% in soils with sand content >80% and OM <1%, but in the soil which gave the
      highest sorption, herbicide residues were not detected at depths >16 cm. The
      herbicidal activity of norflurazon was followed by measuring its bleaching effect
      on soybean plants, and the herbicide concentration required to give 50%
      chlorophyll inhibition (CI(50)) was calculated. CI(50) was achieved on a sandy
      soil with 0.08 mg x kg(-)(1), whereas 1.98 mg x kg(-)(1) was necessary for the
      soil that presented maximum norflurazon adsorption.

PMID- 14969547
TI  - Effect of antioxidant protection of must on volatile compounds and aroma shelf
      life of Falanghina (Vitis vinifera L.) wine.
AB  - Two vinification methods involving different degrees of antioxidant protection of
      Falanghina must during prefermentative steps, and referred as HAMP (high
      antioxidant must protection) and LAMP (low antioxidant must protection), were
      compared in terms of fermentation performances of four different yeast strains,
      composition of the volatile fraction of wines at the end of alcoholic
      fermentation, and shelf life of wines during storage. The use of HAMP technology
      resulted in wines with lower volatile acidity and higher concentrations of medium
      chain fatty acid ethyl esters, acetates, and volatile fatty acids. For two of the
      four strains a lower concentration of isoamyl alcohol was also observed. HAMP
      wines also revealed increased shelf life because of the higher concentration of
      odor active esters at the end of storage and better preservation of varietal
      aromas.

PMID- 14969548
TI  - Metabolites of lesser grain borer in grains.
AB  - Many volatile alcohol and ester metabolites of the lesser grain borer (LGB,
      Rhyzopertha dominica) cultured on wheat grain were identified. Volatiles from
      infested samples at 80 degrees C were collected on Tenax absorbent, thermally
      desorbed, and analyzed by gas chromatography (GC) using infrared (IR) and mass
      (MS) detectors for component identification. A solid-phase microextraction (SPME)
      technique was used to analyze selected samples with a GC-MS system set up for
      obtaining chemical ionization mass spectra. SPME was also used in a synthesis
      process required to identify ester metabolites. Predominant compounds in LGB
      infested grains were 2-pentanol and its esters of 2-methyl-2-pentenoic (A) and
      2,4-dimethyl-2-pentenoic (B) acids, which are known aggregation pheromones,
      dominicalures 1 and 2. 2-Pentanol esters of saturated A, beta-keto- and beta
      hydroxy derivatives of A and B, homologues of A and B, and acid moieties lacking
      the 2-methyl substitution were found. Other straight- and branched-chain
      secondary alcohols and their esters were also observed. Reexamination of GC-MS-IR
      data acquired in previous investigations of LGB cultured on sorghum grain and
      commercial samples in a grain odor study showed the presence of many LGB
      metabolites in addition to the known dominicalures.

PMID- 14969549
TI  - Characterization of corrinoid compounds from a Japanese black tea (Batabata-cha)
      fermented by bacteria.
AB  - A Japanese fermented black tea (Batabata-cha) contained a considerable amount of
      vitamin B(12) (456 +/- 39 ng per 100 g dry tea leaves and 2.0 +/- 0.3 ng per 100
      mL of tea drink). A corrinoid compound was partially purified and characterized
      from the tea leaves. The patterns of the purified compound by the silica gel 60
      thin-layer chromatography and C18 reversed phased high-performance liquid
      chromatography were identical to those of authentic vitamin B(12). When 20 week
      old vitamin B(12) deficient rats, which excreted substantial amounts (about 250
      mg/day) of methylmalonic acid in urine as an index of vitamin B(12) deficiency,
      were fed the tea drink (50 mL/day, 1 ng of vitamin B(12)) for 6 weeks, urinary
      methylmalonic acid excretion (169 +/- 29 mg/day) of the tea drink-supplemented 26
      week old rats decreased significantly relative to that (250 +/- 32 mg/day) of the
      deficient rats. The results indicate that the vitamin B(12) found in the
      fermented black tea is bioavailable in mammals.

PMID- 14969550
TI  - Free radical scavenging behavior of antioxidant compounds of sesame (sesamum
      indicum L.) in DPPH(*) system.
AB  - The free radical scavenging capacity (RSC) of antioxidants from sesame cake
      extract was studied using the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(*)())
      on a kinetic model. Pure lignans and lignan glycosides isolated from methanolic
      extract by preparative HPLC were used in the study. To understand the kinetic
      behavior better and to determine the RSC of sesame antioxidants, the second-order
      rate constant (k(2)) was calculated for the quenching reaction with [DPPH(*)]
      radical. The k(2) values of the sesame antioxidants were compared with those of
      butylated hydroxytoluene and alpha-tocopherol. The k(2) values for sesamol,
      sesamol dimer, sesamin, sesamolin, sesaminol triglucoside, and sesaminol
      diglucoside were 4.00 x 10(-)(5), 0.50 x 10(-)(5), 0.36 x 10(-)(5), 0.13 x 10(
      )(5), 0.33 x 10(-)(5), and 0.08 x 10(-)(5) microM(-)(1) s(-)(1), respectively.

PMID- 14969551
TI  - Glucoraphanin and 4-hydroxyglucobrassicin contents in seeds of 59 cultivars of
      broccoli, raab, kohlrabi, radish, cauliflower, brussels sprouts, kale, and
      cabbage.
AB  - The importance of dietary sulforaphane in helping maintain good health continues
      to gain support within the health-care community and awareness among U.S.
      consumers. In addition to the traditional avenue for obtaining sulforaphane,
      namely, the consumption of appropriate cruciferous vegetables, other consumer
      products containing added glucoraphanin, the natural precursor to sulforaphane,
      are now appearing in the United States. Crucifer seeds are a likely source for
      obtaining glucoraphanin, owing to a higher concentration of glucoraphanin and the
      relative ease of processing seeds as compared to vegetative parts. Seeds of
      several commonly consumed crucifers were analyzed not only for glucoraphanin but
      also for components that might have negative health implications, such as certain
      indole-containing glucosinolates and erucic acid-containing lipids.
      Glucoraphanin, 4-hydroxyglucobrassicin, other glucosinolates, and lipid erucic
      acid were quantified in seeds of 33 commercially available cultivars of broccoli,
      4 cultivars each of kohlrabi, radish, cauliflower, Brussels sprouts, kale, and
      cabbage, and 2 cultivars of raab.

PMID- 14969552
TI  - Pattern similarity analysis of amino acid sequences for peptide emulsification.
AB  - A new computer program for homology similarity search (HSS) was introduced.
      Application of the HSS to peptide sequences of short peptides with fewer 32 amino
      acid residues has explained the underlying mechanism of their emulsifying
      ability. It was found that certain regularity in the frequency of alternate
      polar/apolar cycle with high hydrophobic similarity density was required to
      obtain good emulsion. To supplement this required regularity, charge
      distribution, molecular flexibility, and a structural torsion caused by a proline
      residue might also play roles.

PMID- 14969553
TI  - Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats
      after ingestion of pure compounds and grape juice.
AB  - The present study investigates the bioavailability of resveratrol and quercetin
      in humans, mice, and rats after oral ingestion of grape juice preparations or
      pure aglycones. Oral administration of resveratrol and quercetin to humans
      yielded detectable levels of resveratrol, quercetin, and their derivatives in the
      plasma and urine. Urinary levels of resveratrol, quercetin, and their metabolites
      were observed in human subjects receiving 600 and 1200 mL of grape juice, whereas
      quercetin metabolites were identified in urine samples even after receiving 200
      mL of grape juice. The cumulative amounts of resveratrol and quercetin excreted
      in the urine of mice receiving concentrated grape juice for 4 days were 2.3 and
      0.7% of the ingested doses, respectively. After i.g. administration of
      resveratrol to rats (2 mg/kg), up to 1.2 microM resveratrol was observed in the
      plasma. The study demonstrates that the glycoside forms of resveratrol and
      quercetin in grape juice are absorbed to a lesser extent than the aglycones.

PMID- 14969554
TI  - Antioxidant activity of extracts of black sesame seed (Sesamum indicum L.) by
      supercritical carbon dioxide extraction.
AB  - Antioxidant activities of extracts derived from sesame seed by supercritical
      carbon dioxide (SC-CO(2)) extraction and by n-hexane were determined using
      alpha,alpha-diphenyl-beta-picylhydrazyl (DPPH) radical scavenging and linoleic
      acid system methods. The highest extracted yield was given at 35 degrees C, 40
      MPa, and a CO(2) flow rate of 2.5 mL min(-1) by an orthogonal experiment. The
      yields of extracts increased with increasing pressure, and yields at 40 and 30
      MPa were higher than that by solvent extraction at 46.50%. Results from the
      linoleic acid system showed that the antioxidant activity follows the order:
      extract at 35 degrees C, 20 MPa > BHT > extract at 55 degrees C, 40 MPa > extract
      at 55 degrees C, 30 MPa > Trolox > solvent extraction > alpha-tocopherol. The SC
      CO(2) extracts exhibited significantly higher antioxidant activities comparable
      to that by n-hexane extraction. The extracts at 30 MPa presented the highest
      antioxidant activities assessed in the DPPH method. At 20 MPa, the EC(50)
      increased with temperature, which indicated that the antioxidant activity was
      decreased in a temperature-dependent manner. The significant differences of
      antioxidant activities were found between the extracts by SC-CO(2) extraction and
      n-hexane. However, no significant differences were exhibited among the extracts
      by SC-CO(2) extraction. The vitamin E concentrations were also significantly
      higher in SC-CO(2) extracts than in n-hexane extracts, and its concentrations in
      extracts corresponded with the antioxidant activity of extracts.

PMID- 14969555
TI  - Fatty acid content and juice characteristics in black currant (Ribes nigrum L.)
      genotypes.
AB  - The fatty acid compositions of seeds from 29 black currant genotypes were
      determined using a rapid small-scale procedure. There was interest in alpha
      linolenic, stearidonic, and, especially, gamma-linolenic acid (GLA) contents, and
      most samples showed values between 11.1 and 18.7%, between 2.5 and 4.5%, and
      between 11.6 and 17.4%, respectively. However, six genotypes exhibited gamma
      linolenic contents >18%, and values >20% were recorded in four of these
      genotypes. The fatty acid contents of the six genotypes were also analyzed by
      using a conventional procedure, and only slight differences in fatty acid
      composition were found between the two methods. Although GLA content was not
      strongly correlated with juice parameters, some genotypes had both high GLA
      contents and desirable juice characteristics. The results obtained provide
      evidence that it is possible to select for GLA contents without negatively
      affecting juice quality, and both aspects can be combined in a single cultivar,
      thereby increasing the added value of the whole fruit.

PMID- 14969556
TI  - Role of phosphate and carboxylate ions in maillard browning.
AB  - The Maillard reaction of carbohydrates and amino acids is the underlying chemical
      basis for flavor and color formation in many processed foods. Phosphate and other
      polyatomic anions will accelerate the rate of Maillard browning, and this effect
      has been explained by invoking enhanced proton abstraction from intermediate
      Amadori compounds. In this work, the effect of phosphate and carboxylate ions on
      browning was measured for a series of reducing sugars with and without the
      presence of beta-alanine. Significant browning was observed for sugars alone
      suggesting that polyatomic anions contribute to Maillard browning by providing
      reactive intermediates directly from sugars. A mechanism is proposed for
      decomposition of sugars by polyatomic anions and efforts to trap reactive species
      using o-phenylenediamine (OPD) are described. The results of this study suggest
      how complications may arise from the popular usage of phosphate buffers in the
      study of Maillard reaction kinetics. In addition, the results imply how
      phosphates may be useful for enhancing browning during food processing.

PMID- 14969557
TI  - Alpha-mercaptoketone formation during the maillard reaction of cysteine and [1
      (13)C]ribose.
AB  - The volatiles formed from [1-(13)C]-ribose and cysteine during 4 h at 95 degrees
      C in aqueous phosphate buffer (pH 5) were analyzed by headspace SPME in
      combination with GC-MS. The extent and position of the labeling were determined
      using MS data. The identified volatiles comprised sulfur compounds such as 2
      [(13)C]methyl-3-furanthiol, 2-[(13)CH(2)]furfurylthiol, [1-(13)C]-3
      mercaptopentan-2-one, [1-(13)C]-3-mercaptobutan-2-one, [4-(13)C]-3-mercaptobutan
      2-one, and 3-mercaptobutan-2-one. The results confirm furan-2-carbaldehyde as an
      intermediate of 2-furfurylthiol, as well as 1,4-dideoxypento-2,3-diulose as an
      intermediate of 2-methyl-3-furanthiol and 3-mercaptopentan-2-one. Loss of the C-1
      and C-5 carbon moieties during the formation of 3-mercaptobutan-2-one suggests
      two different mechanisms leading to the key intermediate butane-2,3-dione.

PMID- 14969558
TI  - LC-MS investigation of oxidation products of phenolic antioxidants.
AB  - Two oxidation systems were examined for the oxidation of three groups of phenolic
      antioxidants; five cinnamic acids, two benzoic acids, and two phenols
      characteristic of olive fruits. Periodate oxidation, which is reported to produce
      products similar to polyphenol oxidase, was contrasted with the reactivity of the
      Fenton system, an inorganic source of hydroxyl radicals. Reaction products were
      identified as various quinones, dimers, and aldehydes, but the nature of the
      products differed between the two oxidation systems. Structure-activity effects
      were also observed for the different phenols. All cinnamic acids in this study
      reacted with the Fenton reagent to produce benzaldehydes as the main products,
      with the exception of 5-caffeoylquinic acid. In contrast, periodate oxidation
      gave no reaction with some of the cinnamic acids. Quinone formation was observed
      for the two compounds, caffeic acid and 5-caffeoylquinic acid, possessing o
      hydroxy groups. Caffeic acid was unusual in that dimer formation was the main
      initial product of reaction. Benzoic acids were readily oxidized by both systems,
      but no identifiable products were isolated. Oleuropein was oxidized by both
      oxidants used in this study, resulting in quinones in each system, whereas little
      or no oxidation of tyrosol was observed. This highlights the importance of
      conjugation between the alkene double bond and the hydroxy group. The results
      question the validity of many existing methods of testing antioxidant activity.

PMID- 14969559
TI  - Specific synthesis of 5,5'-dicapsaicin by cell suspension cultures of capsicum
      annuum var. annuum (chili Jalapeno chigol) and their soluble and NaCl-extracted
      cell wall protein fractions.
AB  - HPLC-UV, (1)H NMR, (13)C NMR, and (1)H-(1)H COSY analyses revealed that exogenous
      capsaicin was specifically converted into 5,5'-dicapsaicin by both cell
      suspension cultures of Capsicum annuum var. annuum (chili Jalapeno chigol) and
      their soluble and NaCl-extracted cell wall protein fractions under oxidative
      conditions. In cell suspension cultures 5,5'-dicapsaicin was found only in
      biomass of capsaicin-fed cultures. This compound has not been detected before
      either in fresh fruits or in in vitro cultures of Capsicum. The transformation of
      capsaicin by different protein fractions revealed that most of the enzymatic
      activity was located in the NaCl-extracted, or ionic cell wall bound, protein,
      and that it was strictly dependent on H(2)O(2). These results might in part
      explain some previously described features of capsaicin production by in vitro
      cultures of Capsicum. The implications of the results regarding the catabolism of
      capsaicinoids are discussed.

PMID- 14969560
TI  - Novel fibrinolytic enzyme in fermented shrimp paste, a traditional asian
      fermented seasoning.
AB  - A novel fibrinolytic enzyme was purified from fermented shrimp paste, a popular
      seasoning used in Asian countries. The enzyme is a monomer with an apparent
      molecular weight of 18 kDa, and it is composed primarily of beta-sheet and random
      coils. The N-terminal amino acid sequence was determined to be DPYEEPGPCENLQVA.
      It is a neutral protease with an optimal activity from pH 3 to 7. No inhibition
      was observed with PMSF, Pepstatin A, E64, and 1,10-phenanthroline, but the enzyme
      was slightly inhibited by EDTA and Cu(2+). It was relatively specific to fibrin
      or fibrinogen as a protein substrate, yet it hydrolyzed none of the plasma
      proteins in the studies. In vitro, the enzyme was resistant to pepsin and trypsin
      digestion. It also had an anticoagulant activity measured with activated partial
      thrombin time and prothrombin time tests. The novel fibrinolytic enzyme derived
      from traditional Asian foods is useful for thrombolytic therapy. In addition,
      this enzyme has a significant potential for food fortification and nutraceutical
      applications, such that its use could effectively prevent cardiovascular
      diseases.

PMID- 14969561
TI  - Characterization of interactions between chitosan and an anionic surfactant.
AB  - Chitosan is a cationic biopolymer that has many potential applications in the
      food industry because of its unique nutritional and physiochemical properties.
      Many of these properties depend on its ability to interact with anionic surface
      active molecules, such as phospholipids, surfactants, and bile acids. The purpose
      of this study was to characterize the interaction between chitosan and a model
      anionic surfactant (sodium dodecyl sulfate, SDS) using isothermal titration
      calorimetry (ITC), surfactant-selective electrode (SSE), and turbidity
      measurements. ITC and SSE indicated that SDS bound strongly to chitosan via a
      highly exothermic interaction. The turbidity measurements indicated that chitosan
      formed insoluble complexes with SDS that strongly scattered light. The chitosan
      bound approximately 4 mM of SDS per 0.1 wt % chitosan before becoming saturated
      with surfactant. The SDS-chitosan interaction was weakened appreciably by the
      presence of 100 mM NaCl, which suggested that it was electrostatic in origin.
      This study provides information about the origin and characteristics of molecular
      interactions between chitosan and anionic surface-active lipids that may be
      useful for the rational design of chitosan-based food ingredients with specific
      nutritional and functional characteristics, e.g., cholesterol lowering or fat
      replacement.

PMID- 14969562
TI  - Survey of persistent organochlorine contaminants (PCBs, PCDD/Fs, and PAHs), heavy
      metals (Cu, Cd, Zn, Pb, and Hg), and arsenic in food samples from Huelva (Spain):
      levels and health implications.
AB  - Concentrations of PCBs, PCDDs, and PCDFs, heavy metals (Cu, Cd, Zn, Pb, and Hg),
      and arsenic have been determined in a great variety of food samples purchased in
      different markets across the city of Huelva, located in southwestern Spain and
      under strong industrial activity. All samples analyzed presented concentrations
      below the maximum allowed by the European Community regarding PCDD/Fs, with the
      exception of samples within the meat group. An estimation of the daily intake
      resulted in 1.15 pg of WHO(PCDD/Fs)-TEQ/kg of body weight/day for a 70 kg person
      and 2.63 pg of WHO-TEQ/kg of body weight/day when PCBs were included, therefore
      accounting for a similar or even higher percentage than PCDD/Fs and showing the
      importance of their inclusion in monitoring studies. Meat and meat products,
      together with vegetable oils and dairy products, were the major food groups
      contributing to the estimated daily intake. For heavy metals and arsenic, the
      concentrations found were under the value proposed by European regulations, and
      estimated daily intakes were well below those proposed by the WHO for all metals
      investigated. PAHs have been analyzed in food samples from marine origin, values
      ranging from 8.22 to 71.4 ng/g of fresh weight. Pyrene was the most abundant
      compound, accounting for >80% in the samples investigated. The most carcinogenic
      PAHs, such as benzo[a]pyrene and dibenz[a,h]anthracene, were in all cases below
      the limits of detection. Therefore, the samples analyzed in this survey can be
      considered as safe with regard to the levels obtained and the in-force
      legislation.

PMID- 14969563
TI  - Inhibitory effects of viburnum dilatatum Thunb. (gamazumi) on oxidation and
      hyperglycemia in rats with streptozotocin-induced diabetes.
AB  - The fruit of Viburnum dilatatum Thunb. (gamazumi) was found in a previous study
      to have strong radical scavenging activity. The present study investigated the
      antioxidative functions of gamazumi crude extract (GCE) in rats having diabetes
      induced by the administration of streptozotocin. In rats given water (H(2)O
      group), plasma levels of glucose, total cholesterol, and lipid peroxide (TBARS)
      and erythrocyte levels of TBARS increased with time over the experimental period
      of 10 weeks. These increases were inhibited in rats given GCE (GCE group). After
      10 weeks, hepatic, renal, and pancreatic TBARS in the GCE group were
      significantly lower than those in the H(2)O group. GCE contains a high
      concentration of polyphenols, and it is expected that they are the active
      components. These results demonstrate that GCE has an inhibitory effect on the
      oxidative stress induced by diabetes and suggest that GCE may be useful for the
      prevention of diabetic complications. Furthermore, as the increase of plasma
      glucose and total cholesterol was inhibited in the GCE group, GCE may also have
      anti-hyperglycemic activity in diabetes.

PMID- 14969564
TI  - Antidiabetic activity of red wine polyphenolic extract, ethanol, or both in
      streptozotocin-treated rats.
AB  - A polyphenol extract from a Corbieres (France) red wine (P, 200 mg/kg), ethanol
      (E, 1 mL/kg), or a combination of both (PE) was administered by daily gavage for
      6 weeks to healthy control or streptozotocin (60 mg/kg i.v.)-induced diabetic
      rats (180-200 g). Treatment groups included C or D (untreated control or
      diabetic) and CP, CE, or CPE (treated control) or DP, DE, or DPE (treated
      diabetic). P treatment induced a reduction in body growth, food intake, and
      glycemia in both CP and DP groups. In DP, hyperglycemia was reduced when measured
      1 h after daily treatment but not at sacrifice (no treatment on that day). The
      hyperglycemic response to the oral glucose tolerance test (OGTT) and plasma
      insulin at sacrifice were impaired similarly in DP and D groups. In contrast, in
      DE or DPE, body growth was partially restored while hyperglycemia was reduced
      both during treatment and at sacrifice. In addition, hyperglycemia response to
      OGTT was reduced and plasma insulin was higher in DE or DPE than in D animals,
      indicating a long-term correction of diabetes in ethanol-treated animals.
      Morphometric studies showed that ethanol partially reversed the enlarging effect
      of diabetes on the mesenteric arterial system while the polyphenolic treatment
      enhanced it in the absence of ethanol. In summary, our study shows that (i). a
      polyphenol extract from red wine ("used at a pharmacological" dose) reduces
      glycemia and decreases food intake and body growth in diabetic and nondiabetic
      animals and (ii). ethanol ("nutritional" dose) administered alone or in
      combination with polyphenols is able to correct the diabetic state. Some of the
      effects of polyphenols were masked by the effects of ethanol, notably in diabetic
      animals. Further studies will determine the effect of "nutritional" doses of
      polyphenols as well as their mechanism of action.

PMID- 14969565
TI  - Decrease of heat shock protein levels and cell populations by wine phenolic
      extracts.
AB  - The effect of red and white wine total extracts and phenolic fractions on heat
      shock protein (Hsp) levels in tumor cells and on tumor and endothelial cell
      populations in vitro has been investigated. Total extracts of red wines decreased
      Hsp70 and Hsp27 levels and the numbers of tumor and endothelial cells. Several
      red and white wine fractions significantly decreased Hsp27 levels, and some of
      them had also an effect on Hsp70 levels. A red wine fraction rich in polymeric
      flavanols and a white wine one rich in phenolic acids, flavonols, and tyrosol
      strongly lowered Hsp27 levels. Some red and white wine fractions strongly reduced
      tumor cell numbers, whereas most of them decreased endothelial cell numbers to
      variable extents. The present results indicate that wine phenolics decrease Hsp
      levels in tumor cells and tumor and endothelial cell populations. These
      properties may be important in the potent anticarcinogenic action of wine
      phenolics.

PMID- 14969566
TI  - Presentation, diagnosis, and management of enterovirus infections in neonates.
AB  - The nonpoliovirus enteroviruses commonly infect newborns, with consequences
      ranging from asymptomatic infection and benign illness, to severe, life
      threatening disease. Frequently occurring symptoms include fever, irritability,
      lethargy, anorexia, and rash. Although most illnesses are mild, severe disease
      develops in a subset of newborns infected in the first 2 weeks of life. Severe
      disease may consist of sepsis, meningoencephalitis, myocarditis, pneumonia,
      hepatitis, and/or coagulopathy. Substantial mortality rates have been reported,
      and long-term sequelae may occur among survivors. Risk factors and clinical
      features associated with severe disease include absence of neutralizing antibody
      to the infecting serotype, maternal illness prior to or at delivery, prematurity,
      illness onset within the first few days of life, multiorgan disease, severe
      hepatitis, positive serum viral culture, and specific infecting serotype (e.g.
      group B coxsackieviruses and echovirus 11). Whereas the mainstay of diagnosis has
      traditionally been viral isolation in tissue culture, the polymerase chain
      reaction has been demonstrated to be more sensitive than culture, highly
      specific, and rapid. Immunoglobulin has been used as a therapeutic agent for
      neonates with enterovirus disease; however, clinical efficacy has not been
      proven. Specific antiviral therapy for enteroviruses is in development.
      Pleconaril is an investigational agent that inhibits viral attachment to host
      cell receptors and uncoating of viral nucleic acid. It has broad and potent anti
      enterovirus activity, excellent oral bioavailability, and is well tolerated. Some
      clinical trials have demonstrated benefit in children and adults with enterovirus
      meningitis, and in adults with upper respiratory tract infections caused by
      picornaviruses (rhinoviruses or enteroviruses). Data summarizing compassionate
      use for severe enterovirus diseases (including neonatal sepsis) also suggest
      possible benefit. Limited pharmacokinetic data are available in infants and
      neonates. A multicenter, placebo-controlled, randomized trial of pleconaril in
      neonates with severe hepatitis, coagulopathy, and/or myocarditis is currently
      being conducted.

PMID- 14969567
TI  - Emergency department management of pain and anxiety related to orthopedic
      fracture care: a guide to analgesic techniques and procedural sedation in
      children.
AB  - Orthopedic fractures and joint dislocations are among the most painful pediatric
      emergencies. Safe and effective management of fracture-related pain and anxiety
      in the emergency department reduces patient distress during initial evaluation
      and often allows definitive management of the fracture. No consensus exists on
      which pharmacologic regimens for procedural sedation/analgesia are safest and
      most effective. For some children, control of fracture pain is the primary goal,
      whereas for others, relief from anxiety is an additionally important objective.
      Furthermore, strategies for the management of fracture pain may vary by fracture
      location and patient characteristics; thus, no single regimen is likely to
      provide the best means of analgesia and anxiolysis for all patients. Effective
      analgesia can be provided by local or regional anesthesia, such as hematoma,
      Bier, or nerve blocks. Alternatively, induction of deep sedation with analgesic
      agents such as ketamine or fentanyl, often combined with sedative-anxiolytic
      agents such as midazolam, may be used to manage distress associated with fracture
      reduction. A combination of local anesthesia with moderate sedation, for example
      nitrous oxide, is another attractive option.

PMID- 14969568
TI  - Weight gain associated with atypical antipsychotic use in children and
      adolescents: prevalence, clinical relevance, and management.
AB  - Atypical antipsychotics are increasingly prescribed to children and adolescents
      with neuropsychiatric disorders. Although their profile of potent antagonism at
      specific serotonin and dopamine receptors offers certain advantages compared with
      typical antipsychotics, their use has been associated with various adverse
      effects, including significant weight gain. This adverse effect is of particular
      concern in children and adolescents, secondary to the immediate and long-term
      health risks associated with weight gain, including obesity, diabetes mellitus,
      and hyperlipidemia. Indeed, from 1963 to 1991, the prevalence of obesity has
      approximately doubled in youth. Prior to selecting an atypical antipsychotic, a
      detailed review of the predictors of weight gain is necessary for every child and
      adolescent. Published data suggest that clozapine and olanzapine are associated
      with considerable weight gain, whereas risperidone and quetiapine have a moderate
      risk. Alternatively, ziprasidone and aripiprazole may exhibit a low risk for this
      adverse effect. Whereas behavioral and pharmacologic measures are available to
      manage weight gain associated with atypical antipsychotics, research is needed to
      establish more effective and safe interventions for this adverse effect in
      children and adolescents.

PMID- 14969570
TI  - Giving medicines to children : understanding the parents' views.

PMID- 14969569
TI  - Drug dosing during intermittent hemodialysis and continuous renal replacement
      therapy : special considerations in pediatric patients.
AB  - Chronic renal failure is, fortunately, an unusual occurrence in children;
      however, many children with various underlying illnesses develop acute renal
      failure, and transiently require renal replacement therapy - peritoneal dialysis,
      intermittent hemodialysis (IHD), or continuous renal replacement therapy (CRRT).
      As children with acute and chronic renal failure often have multiple comorbid
      conditions requiring drug therapy, generalists, intensivists, nephrologists, and
      pharmacists need to be aware of the issues surrounding the management of drug
      therapy in pediatric patients undergoing renal replacement therapy. This article
      summarizes the pharmacokinetics and dosing of many drugs commonly prescribed for
      pediatric patients, and focuses on the management of drug therapy in pediatric
      patients undergoing IHD and CRRT in the intensive care unit setting. Peritoneal
      dialysis is not considered in this review. Finally, a summary table with
      recommended initial dosages for drugs commonly encountered in pediatric patients
      requiring IHD or CRRT is presented.

PMID- 14969571
TI  - Progress with novel pharmacological strategies for gastro-oesophageal reflux
      disease.
AB  - Gastro-oesophageal reflux disease (GORD) is a chronic disorder characterised by
      an increased exposure of the oesophagus to intragastric contents. Currently, GORD
      symptoms are maintained under control with antisecretory agents, mainly gastric
      proton pump inhibitors (PPIs). Although impaired oesophageal motility may partly
      underlie the pathophysiology of GORD, the use of prokinetic agents has been found
      to be unsatisfactory. To date, novel pharmacological approaches for GORD are
      mainly related to the control of transient lower oesophageal sphincter (LOS)
      relaxations (TLOSRs). The majority of patients with GORD have reflux episodes
      during TLOSRs, which are evoked by gastric distension, mainly occurring after
      ingestion of a meal. Patients with reflux disease with normal peristalsis and
      without or with mild erosive disease could potentially benefit from anti-TLOSR
      therapy. This therapy might also be of value to treat some severe forms of
      esophagitis in combination with PPIs. GABA-B-receptor agonists are the most
      promising class of agents identified so far for TLOSR control. The GABA-B
      receptor agonist, baclofen, is the most effective compound in inhibiting TLOSRs
      in humans. Since baclofen has several CNS adverse effects, novel orally available
      GABA-B agonists are needed for effective and well tolerated treatment of GORD.
      Endogenous or exogenous cholecystokinin (CCK) causes a reduction in LOS pressure,
      an increase in TLOSR frequency and a reduction in gastric emptying. In healthy
      volunteers and patients with GORD, loxiglumide, a selective CCK1-receptor
      antagonist, was found to reduce the rate of TLOSRs, although its effect on
      postprandial acid reflux may be modest. Orally effective CCK antagonists are not
      marketed to date. The anticholinergic agent atropine, given to healthy volunteers
      and patients with GORD, markedly reduced the rate of TLOSRs. Because of severe
      gastrointestinal (and other) adverse effects of anticholinergics, including
      worsening of supine acid clearance and constipation, it is unlikely that this
      class of drugs will have a future as anti-TLOSR agents on a routine basis. In
      spite of their effectiveness in reducing TLOSR rate, untoward adverse effects,
      such as addiction and severe constipation, currently limit the use of morphine
      and other opioid mu-receptor agonists. The same applies to nitric oxide synthase
      inhibitors, which are associated with marked gastrointestinal, cardiovascular,
      urinary and respiratory adverse effects. Animal studies provide promising
      evidence for the use of cannabinoid receptor 1 agonists, by showing potent
      inhibition of TLOSRs in the dog, thus opening a new route for clinical
      investigation in humans. A better understanding of TLOSR pathophysiology is a
      necessary step for the further development of novel drugs effective for anti
      reflux therapy.

PMID- 14969572
TI  - Allergic fungal sinusitis: pathogenesis and management strategies.
AB  - Allergic fungal sinusitis (AFS) is a noninvasive form of highly recurrent chronic
      allergic hypertrophic rhinosinusitis that can be distinguished clinically,
      histopathologically and prognostically from the other forms of chronic fungal
      rhinosinusitis. There are three invasive (acute necrotising, chronic invasive and
      granulomatous invasive) and two noninvasive (fungal ball and allergic fungal)
      forms of fungal rhinosinusitis currently recognised. Confusion in differentiating
      between the various forms of fungal rhinosinusitis and between other forms of
      chronic hypertrophic sinus disease (HSD) can be eliminated by adhering to strict
      diagnostic criteria. Although there are characteristic presenting clinical
      history and physical examination findings, laboratory test results, including
      elevated total serum IgE and positive inhalant allergy skin tests, and sinus
      computed tomography scans showing chronic rhinosinusitis (often with the presence
      of hyperattenuating sinus contents) diagnosis of AFS is essentially based on
      histopathology obtained from sinus surgery. Histopathology shows the presence of
      eosinophilic-lymphocytic sinus mucosal inflammation, extramucosal allergic mucin
      (that is also seen grossly at surgery as a characteristic 'peanut-buttery'
      material), and scattered silver stain positive fungal hyphae within the allergic
      mucin but not in the mucosa. Treatment and follow up of AFS has been based on its
      immunopathological analogy to allergic bronchopulmonary aspergillosis, a similar
      noninvasive fungal hypersensitivity disorder of the lung, and its clinical and
      pathophysiological relationship to other forms of HSD and asthma. Treatment
      involves aggressive sinus surgery followed by medical management that includes
      allergen immunotherapy, topical and systemic corticosteroids, antihistamines and
      antileukotrienes. Total serum IgE levels should be followed postoperatively as
      they can be prognostic for recurrent disease. Close follow up and coordination of
      treatment by both medical and surgical physicians as a team leads to the best
      clinical outcomes. Ongoing studies are being directed at furthering our
      understanding of the pathophysiological relationships and treatment options for
      AFS, and other common forms of chronic hypertrophic rhinosinusitis disorders.

PMID- 14969573
TI  - Atosiban for preterm labour.
AB  - Oxytocin antagonists are synthetic analogues that have the nonapeptide structure
      of oxytocin. They act by competing with oxytocin for receptors in the myometrium.
      Animal experiments and pilot clinical studies have examined several agents and,
      of these, atosiban has been the object of extensive clinical trials. In a large
      placebo-controlled trial with >500 patients, atosiban reduced the number of
      premature deliveries over 7 days compared with placebo with no more adverse
      effects than placebo. In large multicentre studies comparing atosiban with beta
      adrenoceptor agonists, the efficacy of the two medications was similar for
      pregnancy prolongation for 48 hours and for 7 days. The adverse effects,
      particularly cardiovascular, were considerably more frequent in the patients
      receiving beta-adrenoceptor agonists, who had to stop treatment significantly
      more often than the atosiban recipients. No fetal adverse effects were seen with
      atosiban and, in particular, no effect on baseline fetal heart rate, unlike with
      the beta-adrenoceptor agonists. Neonatal outcome did not differ significantly
      according to the treatment. The usefulness of maintenance treatment after the
      initial 48 hours has not been confirmed. Thus, the effectiveness of oxytocin
      antagonists appears to be similar to beta-adrenoceptor agonists and the former
      are not accompanied by measurable adverse effects. Oxytocin antagonists were
      designed specifically as tocolytics and have been validated by the European Drug
      Agency. They may be the treatment of choice for preterm labour, particularly in
      patients at risk of cardiovascular complications (e.g. multiple pregnancy, heart
      disease, etc.).

PMID- 14969574
TI  - SSRIs versus non-SSRIs in post-traumatic stress disorder: an update with
      recommendations.
AB  - Post-traumatic stress disorder (PTSD) is a highly prevalent (7.8% lifetime rate)
      anxiety disorder with impairment in daily functioning, frequent suicidal
      behaviour and high rates of co-morbidity. Fortunately, PTSD is responsive to
      pharmacotherapy and psychotherapy. The selective serotonin reuptake inhibitors
      (SSRIs) are the most studied medications for PTSD, with the largest number of
      double-blind, placebo-controlled trials. Of the SSRIs, sertraline, paroxetine and
      fluoxetine have been the most extensively studied, with sertraline and paroxetine
      being US FDA-approved for PTSD. These studies have demonstrated that SSRIs are
      effective in short-term trials (6-12 weeks). Furthermore, continuation and
      maintenance treatment for 6-12 months decrease relapse rates. Besides being the
      most studied and effective drugs for PTSD, SSRIs have a favourable adverse effect
      profile, making them the first-line treatment for PTSD. If SSRIs are not
      tolerated or are ineffective, non-SSRIs should be considered. Serotonin
      potentiating non-SSRIs, such as venlafaxine, nefazodone, trazodone and
      mirtazapine, have been evaluated in PTSD only in open-label and case studies.
      Because of their promising results and relatively good safety profile, they
      should be considered as second-line treatment. Monoamine oxidase inhibitors
      (MAOIs) and tricyclic antidepressants (TCAs) have both been evaluated in a small
      number of double-blind, placebo-controlled studies. The results have been
      inconsistent but promising. In the limited comparative studies, MAOIs appeared
      superior to TCAs but patients continued to have residual symptoms. These drugs
      have significant adverse effects, such as cardiovascular complications, and
      safety issues, such as ease of overdose. Therefore, TCAs and MAOIs should be
      considered as third-line treatment. Anticonvulsants have been evaluated in PTSD
      in open-label studies and results have been positive for carbamazepine, valproic
      acid, topiramate and gabapentin. A small double-blind, placebo-controlled study
      demonstrated efficacy of lamotrigine for PTSD. Anticonvulsants should be
      considered where co-morbidity of bipolar disorder exists, and where impulsivity
      and anger predominate. Bupropion (amfebutamone), a predominantly noradrenergic
      reuptake inhibitor, was ineffective in PTSD in an open-label study.
      Benzodiazepines were ineffective in a double-blind, placebo-controlled study
      despite encouraging case reports. They should be avoided or used only short term
      because of potential depressogenic effects, and the possibility that they may
      promote or worsen PTSD. Buspirone, a non-benzodiazepine anxiolytic, was found to
      be effective in PTSD only in open-label studies. Recently, atypical
      antipsychotics were as effective as monotherapy and as an augmenter to SSRIs in
      open-label/case studies and small double-blind, placebo-controlled trials;
      atypical antipsychotics should be considered in PTSD where paranoia or flashbacks
      are prominent and in potentiating SSRIs in refractory cases.

PMID- 14969576
TI  - Budesonide/formoterol: in chronic obstructive pulmonary disease.
AB  - Budesonide/formoterol is a fixed-dose combination of the corticosteroid
      budesonide and the long-acting beta2-agonist formoterol, and is inhaled via the
      Turbuhaler device. In two large, randomised, double-blind, 12-month studies,
      patients with severe chronic obstructive pulmonary disease (COPD) receiving
      budesonide/formoterol 320/9 microg twice daily had a significantly higher forced
      expiratory volume in 1 second (FEV1) and significantly higher morning and evening
      peak expiratory flow at trial endpoint than recipients of budesonide or placebo;
      FEV1 was significantly higher than with formoterol in the larger study. In both
      studies, the rate of COPD exacerbations and exacerbations requiring oral
      corticosteroids was significantly reduced with budesonide/formoterol versus
      formoterol and placebo. Moreover, the time to first exacerbation was
      significantly prolonged with budesonide/formoterol versus all other treatment
      arms in the larger study. At 12 months, significant improvements in health
      related quality-of-life scores were seen with budesonide/formoterol versus
      placebo in both studies. The reduction in total and individual symptom scores was
      significantly greater with budesonide/formoterol than with budesonide or placebo
      in the smaller study. Budesonide/formoterol was generally well tolerated by
      patients with severe COPD. The tolerability profile of the combination was
      similar to that of the individual components with no increase in the incidence of
      adverse events.

PMID- 14969579
TI  - Daptomycin.
AB  - Daptomycin is a lipopeptide antibacterial with rapid in vitro activity against
      Gram-positive cocci. It is approved for use in patients with complicated skin and
      skin structure infections (cSSSIs) caused by specified Gram-positive cocci. In
      vitro, daptomycin was active against Staphylococcus aureus (including meticillin
      resistant strains), Streptococcus pyogenes, S. agalactiae, group C and G beta
      haemolytic streptococci and vancomycin-susceptible Enterococcus faecalis.
      Bactericidal activity in vitro was rapid and concentration dependent. In two
      randomised, investigator-blinded, multicentre trials in patients with cSSSIs,
      intravenous daptomycin 4 mg/kg once daily was as effective as standard therapy
      (intravenous semi-synthetic penicillin 4-12 g/day or vancomycin 1 g 12-hourly).
      Clinical success rates assessed 6-20 days after treatment end were 82.1% in
      daptomycin recipients and 82.9% in recipients of standard therapy (pooled data).
      In patients with cSSSIs, the adverse event profiles of daptomycin and vancomycin
      were similar. Creatine phosphokinase (CPK) levels increased in 2.8% of daptomycin
      recipients and 1.8% of patients who received standard therapy; only one
      daptomycin recipient (0.2%) experienced increased CPK levels and muscle symptoms
      that were not associated with any comorbid factors.

PMID- 14969575
TI  - Idiopathic pulmonary fibrosis: pathogenesis and therapeutic approaches.
AB  - Idiopathic pulmonary fibrosis (IPF), also termed cryptogenic fibrosing
      alveolitis, is a clinicopathological syndrome characterised by cough, exertional
      dyspneoa, basilar crackles, a restrictive defect on pulmonary function tests,
      honeycombing on high-resolution, thin-section computed tomographic scans and the
      histological diagnosis of usual interstitial pneumonia on lung biopsy. The course
      is usually indolent but inexorable. Most patients die of progressive respiratory
      failure within 3-8 years of the onset of symptoms. Current therapies are of
      unproven benefit. Although the pathogenesis of IPF has not been elucidated, early
      concepts focused on lung injury leading to a cycle of chronic alveolar
      inflammation eventuating in fibrosis and destruction of the lung architecture.
      Anti-inflammatory therapies employing corticosteroids or immunosuppressive or
      cytotoxic agents have been disappointing. More recent hypotheses acknowledge that
      sequential alveolar epithelial cell injury is likely to be a key event in the
      pathogenesis of IPF, but the cardinal event is an aberrant host response to wound
      healing. In this context, abnormal epithelial-mesenchymal interactions, altered
      fibroblast phenotypes, exaggerated fibroblast proliferation, and excessive
      deposition of collagen and extracellular matrix are pivotal to the fibrotic
      process. Several clinical trials are currently underway or in the planning
      stages, and include drugs such as interferon-gamma 1b, pirfenidone,
      acetylcysteine, etanercept (a tumor necrosis factor-alpha antagonist), bosentan
      (an endothelin-1 receptor antagonist) and zileuton (a 5-lypoxygenase inhibitor).
      Future therapeutic strategies should be focused on alveolar epithelial cells
      aimed at enhancing re-epithelialisation and on fibroblastic/myofibroblastic foci,
      which play an essential role in the development of IPF. Stem cell progenitors of
      the alveolar epithelial cells and genetic and epigenetic therapies are attractive
      future approaches for this and other fibrotic lung disorders.

PMID- 14969582
TI  - SRC-dependent outside-in signalling is a key step in the process of
      autoregulation of beta2 integrins in polymorphonuclear cells.
AB  - In human PMN (polymorphonuclear cells), challenged by P-selectin, the beta2
      integrin Mac-1 (macrophage antigen-1) promoted the activation of the SRC
      (cellular homologue of Rous sarcoma virus oncogenic protein) family members HCK
      (haematopoietic cell kinase) and LYN (an SRC family protein tyrosine kinase) and
      phosphorylation of a P-110 (110 kDa protein). SRC kinase activity in turn was
      necessary for macrophage antigen-1-mediated adhesion [Piccardoni, Sideri,
      Manarini, Piccoli, Martelli, de Gaetano, Cerletti and Evangelista (2001) Blood
      98, 108-116]. This suggested that an SRC-dependent outside-in signalling
      strengthens the beta2-integrin interaction with the ligand. To support this
      hypothesis further, in the present study, we used the monoclonal antibody KIM127
      or manganese to lock beta2 integrins in a high-affinity state, and homotypic PMN
      adhesion was analysed to monitor beta2-integrin adhesive function. KIM127 or
      manganese induced PMN homotypic adhesion and P-110 phosphorylation. Both these
      processes were abolished by blocking antibodies against the common beta2 chain,
      by a combination of antibodies against alphaL and alphaM or by inhibitors of SRC
      activity. Confocal microscopy showed that activation epitopes were expressed by
      beta2 integrins co-localized with patches of F-actin at the adhesion sites.
      Blockade of SRC kinases or of actin polymerization prevented clustering of
      activated integrins as well as F-actin accumulation. FACS analysis showed that
      SRC inhibitors modified neither basal nor manganese-induced KIM127 binding. An
      SRC-dependent outside-in signalling initiated by beta2 integrins was also
      required for adhesion triggered by interleukin-8. These results confirm the
      hypothesis that an SRC-dependent outside-in signalling triggered by high affinity
      and ligand binding is necessary to stabilize beta2-integrin-mediated adhesion.
      Allowing clustering of activated integrins, SRC might link the high-affinity with
      the high-avidity state. Proline-rich tyrosine kinase-2 appears to be involved in
      this process.

PMID- 14969583
TI  - A novel 110 kDa form of myosin XVIIIA (MysPDZ) is tyrosine-phosphorylated after
      colony-stimulating factor-1 receptor signalling.
AB  - Macrophage colony-stimulating factor (M-CSF or CSF-1) controls the development of
      macrophage lineage cells via activation of its tyrosine kinase receptor, c-Fms.
      After adding CSF-1 to M1 myeloid cells expressing CSF-1R (CSF-1 receptor),
      tyrosine phosphorylation of many cellular proteins occurs, which might be linked
      to subsequent macrophage differentiation. The biological significance and
      characterization of such proteins were explored by a dual strategy comprising two
      dimensional SDS/PAGE analysis of cell lysates of CSF-1-treated M1 cells
      expressing the wild-type or a mutated receptor, together with an enrichment
      strategy involving a tyrosine-phosphorylated receptor construct. In the present
      study, we report the identification by MS of a novel, low-abundance, 110 kDa form
      of myosin XVIIIA (MysPDZ, myosin containing PDZ domain), which appears to be
      preferentially tyrosine-phosphorylated after CSF-1R activation when compared with
      other known isoforms. Receptor mutation studies indicate that CSF-1R-dependent
      tyrosine phosphorylation of p110myosin XVIIIA requires Tyr-559 in the cytoplasmic
      domain of the receptor and is therefore Src-family kinase-dependent. Gelsolin,
      Erp61 protein disulphide-isomerase and possibly non-muscle myosin IIA were also
      tyrosine-phosphorylated under similar conditions. Similar to the more abundant
      p190 isoform, p110 myosin XVIIIA lacks a PDZ domain and, in addition, it may lack
      motor activity. The phosphorylation of p110 myosin XVIIIA by CSF-1 may alter its
      cellular localization or target its association with other proteins.

PMID- 14969584
TI  - Further evidence for the existence of a specific process for the membrane
      transport of anandamide.
AB  - Indirect evidence for the existence of a specific protein-mediated process for
      the cellular uptake of endocannabinoids has been reported, but recent results
      suggested that such a process, at least for AEA [ N -arachidonoylethanolamine
      (anandamide)], is facilitated uniquely by its intracellular hydrolysis by FAAH
      (fatty acid amide hydrolase) [Glaser, Abumrad, Fatade, Kaczocha, Studholme and
      Deutsch (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 4269-4274]. In the present
      study, we show that FAAH alone cannot account for the facilitated diffusion of
      AEA across the cell membrane. In particular, (i) using a short incubation time
      (90 s) to avoid AEA hydrolysis by FAAH, AEA accumulation into rat basophilic
      leukaemia or C6 cells was saturable at low microM concentrations of substrate and
      non-saturable at higher concentrations; (ii) time-dependent and, at low microM
      concentrations of substrate, saturable AEA accumulation was observed also using
      mouse brain synaptosomes; (iii) using synaptosomes prepared from FAAH-deficient
      mice, saturable AEA accumulation was still observed, although with a lower
      efficacy; (iv) when 36 AEA and N -oleoylethanolamine analogues, most of which
      with phenyl rings in the polar head group region, were tested as inhibitors of
      AEA cellular uptake, strict structural and stereochemical requirements were
      needed to observe significant inhibition, and in no case the inhibition of FAAH
      overlapped with the inhibition of AEA uptake; and (v) AEA biosynthesis by cells
      and sensory neurons was followed by AEA release, and this latter process, which
      cannot be facilitated by FAAH, was still blocked by an inhibitor of AEA uptake.
      We suggest that at least one protein different from FAAH is required to
      facilitate AEA transport across the plasma membrane in a selective and bi
      directional way.

PMID- 14969585
TI  - Copper induces increased beta-sheet content in the scrapie-susceptible ovine
      prion protein PrPVRQ compared with the resistant allelic variant PrPARR.
AB  - Prion diseases are characterized by conformational change in the copper-binding
      protein PrP (prion protein). Polymorphisms in ovine PrP at amino acid residues
      136, 154 and 171 are associated with variation in susceptibility to scrapie.
      PrPVRQ [PrP(Val136/Arg154/Gln171)] or PrPARQ [PrP(Ala136/Arg154/Gln171)] animals
      show susceptibility to scrapie, whereas those that express Ala136/Arg154/Arg171
      (PrPARR) show resistance. Results are presented here that show PrPVRQ and PrPARR
      display different conformational responses to metal-ion interaction. At 37
      degrees C copper induced different levels of b-sheet content in the allelic
      variants of ovine full-length prion protein (amino acid 25-232). PrPVRQ showed a
      significant increase in b-sheet content when exposed to copper at 37 degrees C,
      whereas PrPARR remained relatively unchanged. The conversion of a-helical PrPVRQ
      to b-sheet form was shown by CD spectroscopy and the decreased binding of C
      terminal specific monoclonal anti-PrP antibodies. This conversion to an increased
      b-sheet form did not occur with truncated PrPVRQ (amino acids 89-233), which
      demonstrates that additional metal-binding sites outside of the N-terminus may
      not overtly influence the overall structure of ovine PrP. Despite the difference
      in b-sheet content, both the scrapie-susceptible and -resistant allelic forms of
      ovine PrP acquired resistance to proteinase K digestion following exposure to
      copper at 37 degrees C, suggesting the potential for disease-associated PrPARR to
      accumulate in vivo. Our present study demonstrates that allelic variants of ovine
      PrP differ in their structure and response to the interaction with copper. These
      observations will contribute to a better understanding of the mechanism of
      susceptibility and resistance to prion disease.

PMID- 14969586
TI  - The potential function of steroid sulphatase activity in steroid production and
      steroidogenic acute regulatory protein expression.
AB  - The first step in the biosynthesis of steroid hormones is conversion of
      cholesterol into pregnenolone. StAR (steroidogenic acute regulatory) protein
      plays a crucial role in the intra-mitochondrial movement of cholesterol. STS
      (steroid sulphatase), which is present ubiquitously in mammalian tissues,
      including the placenta, adrenal gland, testis and ovary, desulphates a number of
      3beta-hydroxysteroid sulphates, including cholesterol sulphate. The present study
      was designed to examine the effect of STS on StAR protein synthesis and
      steroidogenesis in cells. Steroidogenic activities of COS-1 cells that had been
      co-transfected with a vector for the cholesterol P450scc (cytochrome P450 side
      chain-cleavage enzyme) system, named F2, a StAR expression vector (pStAR), and an
      STS expression vector (pSTS) were assayed. Whole-cell extracts were subjected to
      SDS/PAGE and then to Western blot analysis. pSTS co-expressed in COS-1 cells with
      F2 and pStAR increased pregnenolone synthesis 2-fold compared with that of co
      expression with F2 and pStAR. Western blot analysis using COS-1 cells that had
      been co-transfected with pSTS, F2 and pStAR revealed that StAR protein levels
      increased, whereas STS and P450scc protein levels did not change. The amount of
      StAR protein translation products increased when pSTS was added to an in vitro
      transcription-translation reaction mixture. Pulse-chase experiments demonstrated
      that the 37 kDa StAR pre-protein disappeared significantly ( P <0.01) more slowly
      in COS-1 cells that had been transfected with pSTS than in COS-1 cells that had
      not been transfected with pSTS. The increase in StAR protein level is not a
      result of an increase in StAR gene expression, but is a result of both an
      increase in translation and a longer half-life of the 37 kDa pre-StAR protein. In
      conclusion, STS increases StAR protein expression level and stimulates steroid
      production.

PMID- 14969587
TI  - Hippocampal volume in early onset depression.
AB  - BACKGROUND: Abnormalities in limbic structures have been implicated in major
      depressive disorder (MDD). Although MDD is as common in adolescence as in
      adulthood, few studies have examined youth near illness onset in order to
      determine the possible influence of atypical development on the pathophysiology
      of this disorder. METHODS: Hippocampal volumes were measured in 17 MDD subjects
      (age = 16.67 +/- 1.83 years [mean +/- SD]; range = 13 - 18 years) and 17 age- and
      sex-matched healthy controls (16.23 +/- 1.61 years [mean +/- SD]; 13 - 18 years)
      using magnetic resonance imaging (MRI). RESULTS: An analysis of covariance
      revealed a significant difference between MDD and control subjects (F = 8.66, df
      = 1, 29, P = 0.006). This was more strongly localized to the left hippocampus (P
      = 0.001) than the right hippocampus (P = 0.047). CONCLUSIONS: Our findings
      provide new evidence of abnormalities in the hippocampus in early onset
      depression. However, our results should be considered preliminary given the small
      sample size studied.

PMID- 14969588
TI  - Multivariate relationships between international normalized ratio and vitamin K
      dependent coagulation-derived parameters in normal healthy donors and oral
      anticoagulant therapy patients.
AB  - BACKGROUND AND OBJECTIVES: International Normalized Ratio (INR) is a world-wide
      routinely used factor in the monitoring of oral anticoagulation treatment (OAT).
      However, it was reported that other factors, e. g. factor II, may even better
      reflect therapeutic efficacy of OAT and, therefore, may be potentialy useful for
      OAT monitoring. The primary purpose of this study was to characterize the
      associations of INR with other vitamin K-dependent plasma proteins in a
      heterogenous group of individuals, including healthy donors, patients on OAT and
      patients not receiving OAT. The study aimed also at establishing the influence of
      co-morbid conditions (incl. accompanying diseases) and co-medications (incl.
      different intensity of OAT) on INR. DESIGN AND METHODS: Two hundred and three
      subjects were involved in the study. Of these, 35 were normal healthy donors
      (group I), 73 were patients on medication different than OAT (group II) and 95
      were patients on stable oral anticoagulant (acenocoumarol) therapy lasting for at
      least half a year prior to the study. The values of INR and activated partial
      thromboplastin time (APTT) ratio, as well as activities of FII, FVII, FX, protein
      C, and concentration of prothrombin F1+2 fragments and fibrinogen were obtained
      for all subjects. In statistical evaluation, the uni- and multivariate analyses
      were employed and the regression equations describing the obtained associations
      were estimated. RESULTS: Of the studied parameters, three (factors II, VII and X)
      appeared as very strong modulators of INR, protein C and prothrombin fragments
      F1+2 had moderate influence, whereas both APTT ratio and fibrinogen had no
      significant impact on INR variability. Due to collinearity and low tolerance of
      independent variables included in the multiple regression models, we routinely
      employed a ridge multiple regression model which compromises the minimal number
      of independent variables with the maximal overall determination coefficient. The
      best-fitted two-component model included FII and FVII activities and explained
      90% of INR variability (compared to 93% in the 5-component model including all
      vitamin K-dependent proteins). Neither the presence of accompanying diseases nor
      the use of OAT nor any other medication (acetylsalicylic acid, statins, steroids,
      thyroxin) biased significantly these associations. CONCLUSION: Among various
      vitamin K-dependent plasma proteins, the coagulation factors II, VII and X showed
      the most significant associations with INR. Of these variables, the two-component
      model, including factors II and VII, deserves special attention, as it largely
      explains the overall variability observed in INR estimates. The statistical power
      of this model is validated on virtue of the estimation that the revealed
      associations are rather universal and remain essentially unbiased by other
      compounding variables, including clinical status and medical treatment. Further,
      much broader population studies are needed to verify clinical usefulness of
      methods alternate or compounding to INR monitoring of OAT.

PMID- 14969589
TI  - Methylenetetrahydrofolate reductase and transcobalamin genetic polymorphisms in
      human spontaneous abortion: biological and clinical implications.
AB  - The pathogenesis of human spontaneous abortion involves a complex interaction of
      several genetic and environmental factors. The firm association between increased
      homocysteine concentration and neural tube defects (NTD) has led to the
      hypothesis that high concentrations of homocysteine might be embryotoxic and lead
      to decreased fetal viability. There are several genetic polymorphisms that are
      associated with defects in folate- and vitamin B12-dependent homocysteine
      metabolism. The methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C
      polymorphisms cause elevated homocysteine concentration and are associated with
      an increased risk of NTD. Additionally, low concentration of vitamin B12
      (cobalamin) or transcobalamin that delivers vitamin B12 to the cells of the body
      leads to hyperhomocysteinemia and is associated with NTD. This effect involves
      the transcobalamin (TC) 776C>G polymorphism. Importantly, the biochemical
      consequences of these polymorphisms can be modified by folate and vitamin B12
      supplementation. In this review, I focus on recent studies on the role of
      hyperhomocysteinemia-associated polymorphisms in the pathogenesis of human
      spontaneous abortion and discuss the possibility that periconceptional
      supplementation with folate and vitamin B12 might lower the incidence of
      miscarriage in women planning a pregnancy.

PMID- 14969590
TI  - A comparison of the Nottingham Health Profile and Short Form 36 Health Survey in
      patients with chronic lower limb ischaemia in a longitudinal perspective.
AB  - BACKGROUND: Different generic quality of life instruments such as the Nottingham
      Health Profile (NHP) and the Short Form 36 Health Survey (SF-36) have revealed
      conflicting results in patients with chronic lower limb ischaemia in psychometric
      attributes in short-term evaluations. The aim of this study was to compare the
      NHP and the SF-36 regarding internal consistency reliability, validity,
      responsiveness and suitability as outcome measures in patients with lower limb
      ischaemia in a longitudinal perspective. METHODS: 48 patients with intermittent
      claudication and 42 with critical ischaemia were included. Assessment was made
      before and one year after revascularization using comparable domains of the NHP
      and the SF-36 questionnaires. RESULTS: The SF-36 was less skewed and more
      homogeneous than the NHP. There was an average convergent validity in three of
      the five comparable domains one year postoperatively. The SF-36 showed a higher
      internal consistency except for social functioning one-year postoperatively and
      was more responsive in detecting changes over time in patients with intermittent
      claudication. The NHP was more sensitive in discriminating among levels of
      ischaemia regarding pain and more able to detect changes in the critical
      ischaemia group. CONCLUSION: Both SF-36 and NHP have acceptable degrees of
      reliability for group-level comparisons, convergent and construct validity one
      year postoperatively. Nevertheless, the SF-36 has superior psychometric
      properties and was more suitable in patients with intermittent claudication. The
      NHP however, discriminated better among severity of ischaemia and was more
      responsive in patients with critical ischaemia.

PMID- 14969591
TI  - Analysis of in vivo and in vitro DNA strand breaks from trihalomethane exposure.
AB  - BACKGROUND: Epidemiological studies have linked the consumption of chlorinated
      surface waters to an increased risk of two major causes of human mortality,
      colorectal and bladder cancer. Trihalomethanes (THMs) are by-products formed when
      chlorine is used to disinfect drinking water. The purpose of this study was to
      examine the ability of the THMs, trichloromethane (TCM), bromodichloromethane
      (BDCM), dibromochloromethane (DBCM), and tribromomethane (TBM), to induce DNA
      strand breaks (SB) in (1) CCRF-CEM human lymphoblastic leukemia cells, (2)
      primary rat hepatocytes (PRH) exposed in vitro, and (3) rats exposed by gavage or
      drinking water. METHODS: DNA SB were measured by the DNA alkaline unwinding assay
      (DAUA). CCRF-CEM cells were exposed to individual THMs for 2 hr. Half of the
      cells were immediately analyzed for DNA SB and half were transferred into fresh
      culture medium and incubated for an additional 22 hr before testing for DNA SB.
      PRH were exposed to individual THMs for 4 hr then assayed for DNA SB. F344/N rats
      were exposed to individual THMs for 4 hr, 2 weeks, and to BDCM for 5 wk then
      tested for DNA SB. RESULTS: CCRF-CEM cells exposed to 5- or 10-mM brominated THMs
      for 2 hr produced DNA SB. The order of activity was TBM>DBCM>BDCM; TCM was
      inactive. Following a 22-hr recovery period, all groups had fewer SB except 10-mM
      DBCM and 1-mM TBM. CCRF-CEM cells were found to be positive for the GSTT1-1 gene,
      however no activity was detected. No DNA SB, unassociated with cytotoxicity, were
      observed in PRH or F344/N rats exposed to individual THMs. CONCLUSION: CCRF-CEM
      cells exposed to the brominated THMs at 5 or 10 mM for 2 hr showed a significant
      increase in DNA SB when compared to control cells. Additionally, CCRF-CEM cells
      exposed to DBCM and TBM appeared to have compromised DNA repair capacity as
      demonstrated by an increased amount of DNA SB at 22 hr following exposure. CCRF
      CEM cells were found to be positive for the GSTT1-1 gene, however no activity was
      detected. No DNA SB were observed in PRH or F344/N rats exposed to individual
      THMs.

PMID- 14969592
TI  - Cholesterol-lowering properties of Ganoderma lucidum in vitro, ex vivo, and in
      hamsters and minipigs.
AB  - INTRODUCTION: There has been renewed interest in mushroom medicinal properties.
      We studied cholesterol lowering properties of Ganoderma lucidum (Gl), a renowned
      medicinal species. RESULTS: Organic fractions containing oxygenated lanosterol
      derivatives inhibited cholesterol synthesis in T9A4 hepatocytes. In hamsters, 5%
      Gl did not effect LDL; but decreased total cholesterol (TC) 9.8%, and HDL 11.2%.
      Gl (2.5 and 5%) had effects on several fecal neutral sterols and bile acids. Both
      Gl doses reduced hepatic microsomal ex-vivo HMG-CoA reductase activity. In
      minipigs, 2.5 Gl decreased TC, LDL- and HDL cholesterol 20, 27, and 18%,
      respectively (P < 0.05); increased fecal cholestanol and coprostanol; and
      decreased cholate. CONCLUSIONS: Overall, Gl has potential to reduce LDL
      cholesterol in vivo through various mechanisms. Next steps are to: fully
      characterize bioactive components in lipid soluble/insoluble fractions; evaluate
      bioactivity of isolated fractions; and examine human cholesterol lowering
      properties. Innovative new cholesterol-lowering foods and medicines containing Gl
      are envisioned.

PMID- 14969593
TI  - Primitive Neuroectodermal Tumor (PNET) of the kidney: a case report.
AB  - BACKGROUND: A case of Primitive Neuroectodermal Tumor (PNET) of the kidney in a
      27-year-old woman is presented. Few cases are reported in the literature with a
      variable, nonspecific presentation and an aggressive behaviour. In our case, a
      radical nephrectomy with lymphadenectomy was performed and there was no residual
      or recurrent tumour at 24-month follow-up. METHODS: The surgical specimens were
      formalin-fixed and paraffin embedded. The sections were stained with routinary
      H&E. Immunohistochemistry was performed. RESULTS: The immunohistochemical
      evaluation revealed a diffuse CD99 positivity in the cytoplasm of the neoplastic
      cells. Pankeratin, cytokeratin AE1/AE3, vimentin, desmin, S100, cromogranin were
      negative. The clinical presentation and the macroscopic aspect, together with the
      histological pattern, the cytological characteristic and the cellular
      immunophenotype addressed the diagnosis towards primary PNET of kidney.
      CONCLUSIONS: Since sometimes it is difficult to discriminate between PNET and
      Ewing's tumour, we reviewed the difficulties in differential diagnosis. These
      tumors have a common precursor but the stage of differentiation in which it is
      blocked is probably different. This could also explain their different biological
      behaviour and prognosis.

PMID- 14969594
TI  - Statins in hypercholesterolaemia: a dose-specific meta-analysis of lipid changes
      in randomised, double blind trials.
AB  - BACKGROUND: Statins alter lipid concentrations. This systematic review determined
      the efficacy of particular statins, in terms of their ability to alter
      cholesterol. REVIEW METHODS: PubMed, the Cochrane Library, references lists of
      reports, and reviews were searched (September 2001) for randomised, double blind
      trials of statins for cholesterol in trials of 12 weeks or longer. Mean change in
      total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides was
      calculated using pooled data for particular statins, and for particular doses of
      a statin. Pre-planned sensitivity analyses were used to determine the effects of
      initial concentration of total cholesterol, study duration, the effects of major
      trials, and effects in placebo versus active controlled trials. Information was
      not collected on adverse events. RESULTS: Different statins at a range of doses
      reduced total cholesterol by 17-35% and LDL-cholesterol by 24-49% from baseline.
      Lower doses of statins generally produced less cholesterol lowering, though for
      most statins in trials of 12 weeks or longer there was at best only a weak
      relationship between dose and cholesterol reduction. Duration of treatment and
      baseline total cholesterol concentration did not alter the amount of the benefit
      attained. CONCLUSIONS: Statins are effective medicines and confer benefit to
      patients in terms of primary and secondary prevention of coronary heart disease.
      Reductions in total cholesterol of 25% or more and LDL cholesterol of more than
      30% were recorded for fixed doses of simvastatin 40 mg, atorvastatin 10 mg, and
      rosuvastatin 5 mg and 10 mg.

PMID- 14969595
TI  - Comparison of PCR and clinical laboratory tests for diagnosing H. pylori
      infection in pediatric patients.
AB  - BACKGROUND: Histology and/or culture are generally considered the gold standard
      for the detection of H. pylori infection. Especially in children, these tests may
      result in a false negative outcome because of patchy distribution of the organism
      in the stomach mucosa. We have developed a PCR assay utilizing nested primer
      pairs directed against a subunit of the H. pylori urease gene (ureA). As part of
      a prospective evaluation of diagnostic tests to aid in detecting H. pylori
      infection in children, the aim of this study was to compare our PCR and Western
      blot assays with results obtained from histologic examination of biopsy
      specimens, rapid urease tests, and an FDA approved serologic assay and published
      PCR results to determine if we could validate the assays for diagnostic use on
      our patient population. RESULTS: Gastric biopsy specimens obtained from 101
      pediatric patients were evaluated for the presence of H. pylori using histologic
      techniques, rapid urease (CLOtest) test and the PCR assay. Serum samples from
      each patient were assayed using both ELISA and Western Blot for antibodies to H.
      pylori. A total of 32 patients tested were positive by at least one of the
      methods evaluated. Thirteen patients had positive histology, 13 had a positive
      CLOtest, and 17 patients had positive H. pylori PCR. Out of the 13 CLO positive
      patients, 12 were positive by histologic analysis and all 13 were positive by
      PCR. Results of serologic tests on the same population did not correlate well
      with other assays. Twenty-eight patients showed serologic evidence of H. pylori
      infection, of which 9 were both CLO and histology positive and 12 were positive
      by PCR. Of the seropositive patients, 26 were ELISA positive, 13 were positive by
      Western blot, and 11 by both serologic methods. CONCLUSIONS: The results obtained
      suggest that our nested PCR assay has the specificity and sensitivity necessary
      for clinical application when compared to standard histologic examination and
      rapid urease test. In addition, we found the current commercially available
      approved ELISA method appears unable to accurately detect H. pylori in this
      population. The Western blot assay yielded better concordance with CLOtest and
      histology, but not as good as the nested PCR assay.

PMID- 14969598
TI  - Immunotherapy in systemic primary (AL) amyloidosis using amyloid-reactive
      monoclonal antibodies.
AB  - Heretofore, treatment of patients with primary or light chain-associated (AL)
      amyloidosis has been directed toward reducing the synthesis of the amyloidogenic
      precursor protein through conventional or high-dose cytotoxic antiplasma cell
      chemotherapy. Although such efforts have extended survival, most often the
      prognosis remains exceedingly poor due to the persistence (or progression) of the
      pathologic deposits. The development of murine amyloid-reactive monoclonal
      antibodies (mAbs) has provided another therapeutic approach; namely, passive
      immunotherapy. These reagents, prepared against human light chain-related
      fibrils, recognize an epitope common to the beta-pleated structure of AL and
      other types of amyloid proteins and can effect rapid amyloidolysis when
      administered to mice injected with human AL amyloid extracts. One such prototypic
      antibody, the IgG1kappa mAb 11-1F4, has now been chimerized and is undergoing GMP
      production for an eventual phase I and II clinical trial in patients with AL
      amyloidosis. Demonstration of the therapeutic efficacy of this amyloid-reactive
      mAb would provide an important proof-of-principle that this form of immunotherapy
      also could benefit individuals with other types of inherited or acquired amyloid
      associated disease.

PMID- 14969599
TI  - Radionuclide therapy with iodine-125 and other auger-electron-emitting
      radionuclides: experimental models and clinical applications.
AB  - Auger-electron emitters represent an attractive alternative to beta-particle
      emitters for cancer therapy if they can be placed intracellularly, especially in
      close proximity to (or within) nuclear DNA. Based on investigations in animal
      tumor models, including those for ovarian cancer, bladder cancer, and brain and
      spinal cord tumors, in which the thymidine analog 5-radioiodo-2'-deoxyuridine
      (*IUdR) has been shown to be therapeutically efficacious, it is hypothesized that
      iodine-125 and other Auger-electron-emitting radionuclides might be valuable in
      the treatment of certain malignant diseases, assuming that uptake of the
      radiopharmaceutical by tumor cells exceeds that by normal dividing cells.
      Preliminary patient studies have shown that this requirement can be met partially
      by the locoregional administration of the radiopharmaceutical and metabolic
      modulation of its uptake by tumor cells. Investigators continue to seek molecules
      that can carry Auger-electron emitters to nuclear DNA, especially those
      radionuclides with higher Auger-electron yields and varying half-lives.

PMID- 14969600
TI  - Serum cytokines in metastatic melanoma patients treated with an autologous tumor
      vaccine.
AB  - Short-term autologous tumor vaccines were established and used to treat
      metastatic melanoma patients. Serum samples obtained prior to (week 0) and after
      three vaccinations (week 4) were assayed for interleukin (IL)-2, interferon (IFN)
      gamma, IL-4, and IL-10. Results (mean +/- SD) for 30 patients who had matching
      serum samples obtained at weeks 0 and 4 were: week 0, IL-2, 122 +/- 320 pg/mL;
      IFN-gamma, 0.1 +/- 0.4 IU/mL; IL-4, 10.0 +/- 19 pg/mL; IL-10, 159 +/- 237 pg/mL;
      week 4: 119 +/- 308 for IL-2; 0.1 +/- 0.4 for IFN-gamma; 16 +/- 29 for IL-4, and
      210 +/- 273 for IL-10. Medium conditioned by tumor cell lines demonstrated
      relatively low levels of secreted IL-10 (3.5 +/- 4.2 pg/106 cells/mL/96 hours),
      which would not account for the observed serum levels. In conclusion, the serum
      cytokine pattern from these patients suggests that the immune system is being
      modulated prior to and subsequent to vaccination.

PMID- 14969601
TI  - Myeloprotective effects of different amifostine regimens in rabbits undergoing
      high-dose treatment with 186rhenium-(tin)1,1- hydroxyethylidene diphosphonate
      (186Re-HEDP).
AB  - The aim of this study is to investigate the myeloprotective effects of different
      amifostine regimens in rabbits undergoing high-dose treatment with 186Rhenium
      (tin)1,1-hydroxyethylidene diphosphonate (186Re-HEDP) and to analyze the impact
      of amifostine on the bone uptake of the radiopharmaceutical. All animals were
      treated with 1000 MBq 186Re-HEDP. Group ReA received 500 mg amifostine prior to
      radionuclide therapy, group ReA3 received 3 x 200 mg amifostine 24 hours and 30
      minutes prior to and 24 hours after radionuclide therapy. Group ReC served as
      control receiving no amifostine. Scintigrams were acquired to quantify the
      skeletal uptake of 186Re-HEDP, and platelet and leucocyte counts were measured.
      The mean decrease in platelets was 36% +/- 2%, 37% +/- 3%, and 61% +/- 5% for
      ReA, ReA3, and ReC, respectively. The decrease in ReC was significantly higher
      than in amifostine-treated animals with no difference between ReA and ReA3. For
      the leucocytes the mean decrease was 75% +/- 12%, 82% +/- 5%, and 73% +/- 4%,
      with no significant differences between the respective groups. Bone uptake of
      186Re-HEDP was significantly reduced by 50% in ReA and ReA3 compared to ReC.
      Thus, the 3-day amifostine regimen had no advantage over the single dose regimen,
      with both regimens reducing bone uptake and yielding a platelet-protective but no
      leucoprotective effect.

PMID- 14969602
TI  - In vivo and in vitro detection of dopamine d2 receptors in uveal melanomas.
AB  - Scintigraphy with radiolabeled benzamides was used in melanoma patients. Studies
      with a newer benzamide called 123I-epidepride, a high-affinity D2 receptor (D2R)
      antagonist, showed high sensitivity in D2R-positive pituitary adenomas. We
      evaluated the presence of D2R in patients with uveal melanomas in vivo with 123I
      epidepride, and in vitro in melanomas, using immunohistochemistry (IHC) and 125I
      epidepride autoradiography. We studied the in vivo tumor-to-background (TB)
      ratios in six patients with posterior uveal melanoma (one previously enucleated).
      IHC was performed in 3 of 6 tumors after enucleation and in another 20 uveal
      melanomas, 7 metastatic lymph nodes from skin melanoma, and 2 normal specimens.
      125I-epidepride autoradiography was performed in 10 uveal melanomas (3 of which
      were studied in vivo), 7 metastases, and 2 normal samples. Radioligand uptake was
      present in the affected eye of 5 patients with uveal melanoma (TB = 3.1-6.1) and
      absent in the operated one (TB = 1). Eight uveal tumors were positive at IHC
      (35%), 14 weakly positive (61%), and 1 negative (4%). Two metastases were
      positive (29%), 2 weakly positive (29%), and 3 negative (42%). Two uveal tumors
      were positive at autoradiography (20%), 7 had nonspecific binding (70%), and 1
      was negative (10%). One metastasis was positive (14%), while 6 were negative
      (86%). 123I-epidepride scintigraphy in uveal melanomas seems promising for
      sensitivity and image quality. D2R was demonstrated in a significant proportion
      of the melanomas, although 123I-epidepride uptake might also be nonspecific and
      unrelated to D2R binding. Although further studies on larger series are needed,
      123I-epidepride could represent a future tool to study the expression of D2R in
      other classes of neuroendocrine tumors.

PMID- 14969603
TI  - Curative potential of foremost mitogen applications.
AB  - This paper is presented as a sequel to the Mitogen Information Summaries article,
      representing a condensation of salient features involved with facilitating the
      curative potential of the more important mitogen applications. Following is a
      resume of the critical attributes of mitogen therapy relative to the management
      of malignant tumors: (1) An inherent capability to recognize and destroy mutated
      or damaged tissues without altering those that are normal; (2) The capacity to
      induce global immunostimulation by the nonspecific activation of CD4+/- and CD8+/
      cells with balanced production of a variety of cytokines able to stimulate B
      cell, NK cell, and macrophage pathways, at the same time augmenting
      myeloproliferation; (3) The ability to afford protection and accelerated recovery
      from the immunosuppressive and myelosuppressive effects of tumors, infections,
      GvH reactions, and autoimmune states along with the surgery, irradiation,
      chemotherapeutic agents, antibiotics, and suppressive factors used in their
      management; (4) Berke's in vitro data from the lectin-dependent cellular
      cytotoxicity (LDCC) system showing that systemic administration of mitogens such
      as PHA-L4 should indeed prove destructive to virtually any type of malignancy,
      leaving normal tissues undamaged; and (5) The potential of these activities to
      reconstitute the immune competence so vital to lasting cures. The potential role
      of L4 immunotherapy for infections may be defined by the following criteria:
      those, including drug-resistant infections, not satisfactorily treatable
      otherwise; those in which a rapid response is essential; those that are
      subclinical, latent, recurrent, chronic, persistent, highly lethal, or
      opportunistic; those in patients with impaired immune responses; and most
      importantly, those that are not likely to be adversely affected by
      immunostimulation. Certain paths of administration such as the intralesional (for
      granulomas), intrapleural (for pleurisy, empyema), and intraperitoneal (for
      peritonitis) routes might be tested as supplements to intravenous administration
      in treating infections using dosages comparable to tumor therapy. Intradermal or
      dermal applications might be used alone for localized viral or fungal skin
      lesions. The comparative advantages of each mitogen are listed as follows: PHA
      L4, longest experience and most complete, including use in humans; Fraction IV
      PHA, nonagglutinating, otherwise comparable to L4; PWM, nonagglutinating in the
      broad mitogenic range, high potency that reduces dosage requirements,
      noncommercial product preferable for experimental studies and for potential
      advancement to human use.

PMID- 14969604
TI  - Treatment with Alstonia scholaris enhances radiosensitivity in vitro and in vivo.
AB  - The radiosensitizing effect of 5 micrograms/mL of alkaloid fraction of Alstonia
      scholaris (ASERS) was evaluated in various neoplastic cell lines, namely: HeLa,
      HePG2, HL60, MCF-7, and KB exposed to 0, 0.5, 1, 2, 3, and 4 Gy of gamma
      radiation. The irradiation of various cells caused a dose-dependent elevation in
      the cytotoxicity, and a maximum cytotoxic effect was observed at 4 Gy (the
      highest dose) in all the cell lines studied. The ASERS pretreatment increased the
      effect of radiation as evidenced by enhanced cell killing when compared with the
      concurrent phosphate-buffered saline (PBS) treated irradiation group. The
      greatest elevation in cell killing was observed for HeLa and KB cells, followed
      by HL60, MCF7, and HePG2 cells. The in vitro observations were confirmed by in
      vivo studies, where the Ehrlich ascites carcinoma (EAC) bearing mice were treated
      with 120 mg/kg body weight of ASERS before exposure to 0, 1, 2, 4, 6, and 8 Gy of
      hemibody (below the rib cage) gamma-radiation. Irradiation of EAC mice caused a
      dose-dependent tumor regression, as evidenced by increased life span of the
      animals. The pretreatment of tumor-bearing animals with 120 mg/kg ASERS resulted
      in a further remission in the tumor when compared with the concurrent nondrug
      treated irradiated controls; as a result there was a radiation dose-dependent
      increase in the life span of tumor-bearing animals receiving 120 mg/kg ASERS,
      except for 8 Gy, where it was less than the concurrent control. The above
      findings corroborate with a time-dependent decrease in the glutathione (GSH)
      contents, accompanied by an increase in lipid peroxidation. Our study
      demonstrates that ASERS treatment enhances the effect of radiation and results in
      disease-free survival of the mice.

PMID- 14969605
TI  - Tumor targeting properties of indium-111 labeled genetically engineered Fab' and
      F(ab')2 constructs of chimeric tumor necrosis treatment (chTNT)-3 antibody.
AB  - Genetic engineering techniques have allowed the construction of Fab' and F(ab')2
      constructs of chimeric tumor necrosis treatment antibody (chTNT-3), a chimeric
      monoclonal antibody (MAb) that targets necrotic regions of solid tumors. The
      purpose of this study is to evaluate the in vitro and in vivo properties of Fab'
      and F(ab')2 constructs radiolabeled with indium-111 (111In) using
      diethylentriamine pentaacetic acid (DTPA) conjugation to develop a clinically
      useful imaging agent for the detection of necrosis in solid tumors. Optimization
      of the MAb-to-DTPA ratio showed that a 1:2 ratio gave the best immunoreactivity
      while providing good radiolabeling efficiency and high specific activity for all
      three DPTA conjugates. In addition, 111In-labeled Fab' and F(ab')2 conjugates
      were found to have faster whole body clearance times and better biodistribution
      profiles compared to parental 111In-labeled chTNT-3 in tumor-bearing mice.
      Although radiolabeled Fab' and F(ab')2 constructs showed lower tumor uptake than
      radiolabeled chTNT-3, biodistribution results showed that these constructs had
      significantly lower uptake in liver, spleen, and other normal organs (except the
      kidney), and therefore had higher tumor-to-organ ratios. In addition, a
      comparison of all derivatives showed that the F(ab')2 reagent gave the best
      results in tumor imaging studies. These results demonstrate that stable, a
      genetically engineered F(ab')2 construct can be successfully radiolabeled with
      111In to produce potential imaging reagents for the imaging and monitoring of
      tumor necrosis.

PMID- 14969606
TI  - Pharmacokinetics in mice of four oligomer-conjugated polymers for amplification
      targeting.
AB  - For use in amplification targeting, an oligomer-conjugated polymer must display
      adaptable chemistry, minimal steric hindrance, low toxicity, and favorable
      pharmacokinetics. In particular, the polymer must remain in circulation
      sufficiently long to permit target localization. OBJECTIVES: To evaluate their
      properties for amplification targeting, the biodistribution in normal mice was
      determined for four polymers conjugated with multiple copies of a
      phosphorodiamidate morpholino (MORF) oligomer. METHODS: An amine-derivatized 25
      mer MORF oligomer was radiolabeled with 99mTc. Three polymers of succinylated
      polylysine (PL) with initial weight average molecular weights (Mw) of 30, 100,
      and 200 KDa, and one poly (methyl vinyl ether-alt-maleic acid) (PA) with initial
      Mw of 45 KDa polymer, were each conjugated with an amine derivatized 25-mer
      complementary MORF (i.e., cMORF). The average number of attached cMORF groups on
      each polymer molecule (i.e., gpm) was estimated by a high performance liquid
      chromatography (HPLC) shift assay after the addition of trace 99mTc-MORF to the
      unpurified polymer, while the average number of accessible cMORF on each polymer
      was determined by adding radiolabeled MORF at increasing concentrations to the
      purified cMORF polymer solution until saturation. After purification, each
      polymer was radiolabeled by incubation with trace 99mTc-MORF. The biodistribution
      was then established in normal CD1 mice at a constant dosage of 2-4 micrograms of
      cMORF. RESULTS: The gpm varied from about 12 on 30 KDa PL to 40 on 45 KDa PA. The
      biodistribution results show that the pharmacokinetics of the radiolabel is a
      function of both the type of polymer as well as its gpm. Of the four polymers,
      the 30 KDa PL showed the most favorable pharmacokinetic profile, with the lowest
      liver accumulation and the highest blood values compared to the remaining three
      polymers. CONCLUSION: The biodistribution of the four polymers showed
      characteristic differences, with one polymer (30 KDa PL) showing the most
      favorable properties for amplification targeting.

PMID- 14969607
TI  - Experimental evidence for the existence of the passive antitumor defense system
      formed by the synergistic action of certain small substances of the circulatory
      system.
AB  - In AIDS, only a few types of tumors (mainly Kaposi's sarcoma and non-Hodgkin's
      lymphoma) increase in incidence despite global abnormalities in the immune
      system. In addition, the reason for the higher incidence of these tumors is not
      immunosuppression but other agents. This shows that the immune system has no
      absolute role in the prevention of tumors. Consequently, the fact that tumors do
      not develop in the majority of the population during their lifetime, indicates
      the existence of other defense system(s). We demonstrated previously that a
      mixture of 16 substances (selected experimentally out of 89 compounds of the
      circulatory system using the synergistic tumor cell-killing effect as criteria)
      had a cytotoxic effect (inducing apoptosis) in vitro and in vivo on tumor cell
      lines, but not on normal cells in vitro or animals. In our hypothesis these
      substances (L-tryptophan, L-tyrosine, L-methionine, L(-)malate, L-ascorbate, L
      arginine, L-phenylalanine, L-histidine, 2-deoxy-D-ribose, d-biotin, pyridoxine,
      adenine, riboflavin, D(+)-mannose, orotate, and hippurate) are the active agents
      of a passive antitumor defense system (PADS). On the basis of the results, a
      tablet and a cream were developed, and an infusion is in preclinical phase. In
      this study we demonstrate that the above-mentioned substances can kill tumor
      cells when the experimental protocols, concentrations, and cell numbers are
      chosen to be comparable to the physiological conditions that exist in the living
      system when these substances fight against arising cancer cells. The results of
      our experiments demonstrate that the PADS really works in the human body.

PMID- 14969608
TI  - Comparison of baseline characteristics and one-year outcomes between African
      Americans and Caucasians undergoing percutaneous coronary intervention.
AB  - The objectives of this study were to determine whether there are race-based
      differences in baseline characteristics and in short- or long-term outcomes after
      percutaneous coronary intervention (PCI). African-Americans have a higher
      incidence of coronary artery disease but are less likely to undergo coronary
      revascularization than Caucasians. Little is known about the profiles and
      outcomes of African-Americans who undergo PCI. Consecutive series of 1,268
      African-Americans and 10,561 Caucasians with symptomatic coronary artery disease
      who underwent PCI between January 1994 and June 2001 were analyzed. Patients
      hospitalized for acute myocardial infarction were excluded. African-Americans
      were older, were more likely to be women, and had more co-morbid baseline
      conditions compared with Caucasians. Preprocedure lesion characteristics were
      similar with regard to vessel size, length, and complexity. The rate of clinical
      success did not differ between the groups. African-Americans experienced more in
      hospital combined events of death and Q-wave myocardial infarction (p = 0.03).
      After propensity score adjustment, African-American race was not an independent
      predictor for in-hospital events. At 1 year, African-Americans had a slightly
      lower rate of target lesion revascularization and a 50% higher rate of death
      (9.8% vs. 6.4%, p <0.001), with a relative risk of 1.52 (95% confidence interval
      1.22 to 1.89). In multivariate analysis, African-American race remained a
      significant predictor of increased 1-year mortality (hazard ratio 1.35, 95%
      confidence interval 1.06 to 1.71, p = 0.01). African-Americans undergoing
      angioplasty have more co-morbid baseline conditions than Caucasians. Despite
      similar clinical success, 1-year outcomes are impaired in African-Americans.

PMID- 14969609
TI  - Comparison of functional recovery of mildly hypokinetic versus severely
      dysfunctional left ventricular segments after revascularization in patients with
      ischemic cardiomyopathy.
AB  - Dysfunctional left ventricular (LV) segments showing contractile reserve during
      dobutamine stress echocardiography (DSE) are considered viable myocardium;
      functional recovery is expected after revascularization. Many segments, however,
      particularly mildly hypokinetic segments, do not recover. The reason for this
      failure is unknown. Two-dimensional echocardiography at rest and low-high-dose
      DSE were performed before revascularization in 114 consecutive patients with
      ischemic cardiomyopathy. Two-dimensional echocardiography at rest was repeated
      after 9 to 12 months. Segmental function was scored by a 5-point grading score.
      Functional recovery after revascularization was assessed in mildly hypokinetic
      (score 2, group I) and severely dysfunctional segments (score 3 to 5, group II).
      For each segment, functional recovery was defined as an improvement in functional
      score of > or =1 grade compared with the baseline score at rest. During low-dose
      DSE (up to 10 microg/kg/min), 183 group I segments (68%) and 438 group II (39%)
      segments had contractile reserve (p <0.0001). However, functional recovery was
      observed less frequently in group I segments (41%) than in group II segments
      (55%) with contractile reserve (p <0.005). During high-dose DSE (up to 40
      microg/kg/min), in the group I segments with contractile reserve at the low dose,
      the sustained improvement pattern (indicating subendocardial scar) was prevalent
      (73%). After revascularization, 73% of segments with sustained improvement did
      not recover. Conversely, the biphasic response (indicating ischemically
      jeopardized myocardium) was observed only in 27% of group I segments. Functional
      recovery occurred in 39 of these segments (78%) (p <0.001 vs sustained
      improvement). Hence, mildly hypokinetic segments probably indicate the presence
      of subendocardial scars, and may explain the failure in functional recovery after
      revascularization.

PMID- 14969610
TI  - Comparison of survival after successful percutaneous coronary intervention of
      patients with diabetes mellitus receiving insulin versus those receiving only
      diet and/or oral hypoglycemic agents.
AB  - The influence of diabetic treatment status on long-term outcome after
      percutaneous coronary intervention (PCI) is unclear. Previous reports have
      suggested that patients who receive insulin treatment have worse long-term
      outcome compared with patients who do not need insulin. To determine the
      influence of diabetes treatment status on outcome after PCI, patients with
      diabetes mellitus who underwent successful PCI from January 1, 1996, to June 30,
      2001, were divided into 2 groups based on whether or not they required insulin;
      patients with shock or recent (< or =7 days) myocardial infarction were excluded.
      Cox proportional hazards models were utilized to estimate the association between
      diabetes treatment status and long-term survival. One thousand one hundred four
      eligible diabetic patients were identified and divided into those treated with
      insulin (418 patients; median follow-up 35.5 months) and those treated with
      either an oral agent or diet alone (686 patients; median follow-up 27.9 months).
      Insulin-treated patients were less likely to be men, and had more previous
      coronary revascularizations, prior myocardial infarctions, and congestive heart
      failure on presentation. Angiographic and procedural characteristics were
      comparable. Unadjusted survival curves were constructed, demonstrating that
      insulin treatment was associated with worse survival than noninsulin treatment (p
      = 0.001). After adjusting for differences in baseline characteristics, insulin
      treatment did not adversely effect survival (odds ratio 1.10, 95% confidence
      intervals 0.77 to 1.58). Thus, among diabetic patients who underwent successful
      PCI, patients treated with insulin had worse survival. After adjusting for
      differences in baseline characteristics, insulin treatment was not independently
      associated with worse survival.

PMID- 14969611
TI  - Relative benefit of coronary artery bypass grafting versus stent-assisted
      percutaneous coronary intervention for angina pectoris and multivessel coronary
      disease in women versus men (one-year results from the Stent or Surgery trial).
AB  - Information on the relative benefit of coronary artery bypass grafting (CABG)
      versus stent-assisted percutaneous coronary intervention (PCI) for improvement of
      cardiac-related health status in women and how it compares with men is limited.
      The Stent or Surgery trial compared randomly assigned CABG and stent-assisted PCI
      in 206 women and 782 men with multivessel disease. We examined longitudinal
      changes at 6 and 12 months from baseline by gender and treatment in 3 subscales
      of the Seattle Angina Questionnaire (SAQ): physical limitation, angina frequency,
      and quality of life. At the time of revascularization, women were older, more
      severely ill, and tended to have lower SAQ scores than men. At 6 months, SAQ
      scores after both procedures improved significantly in both genders, with greater
      improvement achieved with CABG. After adjustment for other factors, in men, CABG
      was associated with a 54.7% greater improvement in physical limitation compared
      with PCI, 31.3% greater improvement in angina frequency, and 18.3% greater
      improvement in quality of life. In women, these relative differences were 11.6%,
      43.2%, and 39.3%, respectively. At 1 year, men continued to show greater
      improvement with CABG in all 3 dimensions (50.6%, 19.7%, and 15.3%,
      respectively), but in women the relative differences decreased substantially
      (1.6%, 11.1%, and 0.6%, respectively) due to a greater later improvement after
      PCI (p = 0.049 for the interaction among treatment, gender, and follow-up for the
      quality of life domain). Although CABG may be superior to PCI in men, in women,
      at 1 year after intervention, both procedures appear equally effective.

PMID- 14969612
TI  - Comparison of coronary artery specific leukocyte-platelet conjugate formation in
      unstable versus stable angina pectoris.
AB  - This study evaluates transcoronary changes in neutrophil and platelet activation
      and conjugate formation in patients with angina pectoris secondary to coronary
      artery disease. We examined parameters of neutrophil and platelet activation as
      well as the neutrophil-platelet conjugate formation in patients who underwent
      diagnostic coronary angiography. Thirty-nine patients with chest pain referred
      for cardiac catheterization were studied (23 patients with unstable angina
      pectoris [UAP] and 16 with stable angina pectoris [SAP]). Before coronary
      angiography, blood samples were obtained simultaneously from the aortic root and
      coronary sinus to assess leukocyte (CD11b) and platelet (CD62P) activation and
      leukocyte-platelet conjugates. There was a 94% increase in CD62-expressing
      platelets from the aorta to the coronary sinus in patients with UAP compared with
      a 49% increase in patients with SAP. The percentage of neutrophil-platelet
      conjugates increased by 22% in patients with UAP compared with a 16% decrease in
      those with SAP (p <0.01). In contrast, monocyte-platelet binding across the
      coronary bed increased to a similar degree in both groups. This study
      demonstrates an increase in neutrophil-platelet conjugates across the coronary
      circulation in UAP, compatible with a higher activation state in both cell types.

PMID- 14969613
TI  - Effect of simvastatin in familial hypercholesterolemia on the affinity of
      electronegative low-density lipoprotein subfractions to the low-density
      lipoprotein receptor.
AB  - The effect of simvastatin therapy on the biologic characteristics of the
      electronegative low-density lipoprotein (LDL) subfraction of patients with
      familial hypercholesterolemia (FH) was studied. Total LDL, isolated from FH
      plasma at 0, 3 and 6 months of simvastatin treatment, was subfractionated into
      electropositive LDL (LDL[+]) and electronegative LDL (LDL[-]) by anion exchange
      chromatography. LDL isolated from healthy normolipemic (NL) subjects was used as
      a control. The LDL(-) proportion was twofold higher in patients with FH than in
      NL subjects (17.6 +/- 1.6% vs 7.8 +/- 1.5%, respectively; p <0.05) and was
      progressively reduced by simvastatin therapy (15.7 +/- 1.6% at 3 months; 13.8 +/-
      2.5% at 6 months; p <0.05). Both LDL subfractions from patients with FH had a
      higher relative cholesterol content and decreased apolipoprotein B and
      triglycerides than NL subfractions. Simvastatin progressively induced changes in
      lipid content of both LDL subfractions in patients with FH, and lipid composition
      was closer to these subfractions in NL subjects after 6 months of therapy.
      Binding displacement experiments in human fibroblasts demonstrated that LDL(-)
      from both groups of subjects had a lower affinity of binding to the LDL receptor
      that LDL(+). In addition, LDL(+) in patients with FH presented an intermediate
      binding affinity between LDL(-) and LDL(+) in NL subjects. Simvastatin-induced
      changes in LDL composition were accompanied by a progressive increase in affinity
      of LDL(+) and LDL(-) in patients with FH. After 6 months of therapy, LDL(+) in FH
      had an affinity similar to that of LDL(+) in NL subjects. The LDL(-)-induced
      release of chemokines interleukin-8 and monocyte chemotactic protein-1 from
      cultured endothelial cells was twofold higher compared with that of LDL(+). No
      difference in chemokine release between patients with FH and NL subjects or the
      effect of simvastatin were observed. We conclude that simvastatin therapy was
      able to modify LDL subfraction composition in subjects with FH and increase their
      affinity to the LDL receptor. This improvement could contribute to the observed
      reduction in LDL(-) proportion induced by simvastatin.

PMID- 14969614
TI  - Association of aortic valve calcium detected by electron beam computed tomography
      with echocardiographic aortic valve disease and with calcium deposits in the
      coronary arteries and thoracic aorta.
AB  - We conducted electron beam computed tomographic (EBCT) testing in a
      representative sample of 327 Framingham Heart Study subjects without clinical
      cardiovascular disease. EBCT was compared with 2-dimensional echocardiography for
      the detection of degenerative aortic valve (AV) disease. We determined the
      association between EBCT measures of AV calcium and calcium deposits in the
      coronary arteries and thoracic aorta. Of 327 subjects (mean age 60 +/- 9 years;
      51% men), 14% had EBCT AV calcium (median Agatston score 0, range 0 to 1,592).
      The prevalence of AV calcium increased predictably across decades of age.
      Compared with echocardiography, the sensitivity and specificity of EBCT for the
      detection of degenerative AV disease were 24% and 94%, respectively. In
      unadjusted logistic regression models, the prevalence of EBCT AV calcium
      increased across tertiles of coronary artery calcium (for trend across tertiles,
      odds ratio [OR] 2.2, 95% confidence interval [CI] 1.4 to 3.5) and thoracic aorta
      calcium (for trend OR 2.8, 95% CI 1.7 to 4.4). After adjustment for age and
      gender, the associations of AV calcium with coronary calcium and thoracic aorta
      calcium were attenuated and no longer statistically significant. Thus, compared
      with echocardiography, EBCT was specific but insensitive for the detection of
      degenerative AV disease. EBCT AV calcium was associated with calcium deposits in
      the coronary arteries and the thoracic aorta, but these associations were
      confounded by age and risk factors.

PMID- 14969615
TI  - Incidence of thrombus formation on the CardioSEAL and the Amplatzer interatrial
      closure devices.
AB  - Transcatheter closure for atrial septal defect (ASD) and patent foramen ovale
      (PFO) is a promising alternative to surgical closure or anticoagulant therapy. A
      potential complication is thrombus formation on the device after implantation.
      From February 2001 to June 2003, 66 patients with atrial communication were
      treated successfully with the Amplatzer device (16 septal and 20 PFO occluders)
      or the CardioSEAL device (30). Patients were discharged on antiplatelet
      medication (aspirin and clopidogrel) and/or anticoagulation. Fifty patients (76%)
      had transesophageal echocardiography (TEE) 1 month after device implantation (28
      +/- 10 days). No patient experienced a thromboembolic episode during follow-up.
      TEE revealed that thrombus formation occurred more frequently on the CardioSEAL
      device (5 of 23 patients; 22%) than on the Amplatzer device (0 of 27 patients;
      0%) (p = 0.02). Although thrombus disappeared or markedly diminished after
      additional anticoagulation therapy in 3 patients, 1 patient had surgical
      explantation of the device due to progressive increase in the size of thrombus
      with hypermobility despite intensive anticoagulation therapy. There was no
      variable associated with the presence of thrombus formation on the occluder other
      than the use of the CardioSEAL device. One month after insertion, the CardioSEAL
      device is more likely to have thrombus present than the Amplatzer device.

PMID- 14969616
TI  - Signal-averaged electrocardiogram in Ebstein's anomaly.
AB  - We sought to establish pathogenetic links between electrophysiology,
      histopathology, and ventricular tachyarrhythmias in patients with Ebstein's
      anomaly. The atrialized right ventricle (ARV) is the site of mechanically
      inducible ventricular tachyarrhythmias, but relations between the arrhythmogenic
      substrate, the type of tachyarrhythmias, and the trigger(s) have not been
      established. This study comprised 23 patients (10 men and 13 women; aged 18 to 58
      years; mean 32 +/- 3) who did not undergo surgery and 6 pre- and postoperative
      patients with Ebstein's anomaly, diagnosed by transthoracic and transesophageal
      echocardiography. Twenty-one patients had classic Ebstein's anomaly and 2 had
      mild forms. Signal-averaged electrocardiograms (SAECGs) identified slow
      conduction by using 3 time-domain variables calculated by an automated algorithm
      and inspected visually. Two variables were required to establish the presence of
      late potentials. SAECGs were repeated in 6 patients after surgical exclusion of
      the ARV. Five surgical specimens of the ARV and the true right atrium were
      examined histologically. Mathematic simulations were used to illustrate anchored
      and unanchored spiral/scroll waves. SAECGs were positive in 21 patients with
      classic Ebstein's anomaly and were negative postoperatively in the 6 so studied.
      The ARV was characterized histologically by clusters of cardiomyocytes isolated
      within a fibrous matrix. We hypothesize that SAECGs identify slow conduction
      residing in the ARV, and that excitation of this arrhythmogenic substrate
      provokes spiral/scroll waves that cannot anchor because clusters of
      cardiomyocytes are isolated within a fibrous matrix. The waves meander
      erratically as polymorphic ventricular tachycardia or break up into ventricular
      fibrillation.

PMID- 14969617
TI  - Comparison of intracardiac echocardiography versus transesophageal
      echocardiography guidance for percutaneous transcatheter closure of atrial septal
      defect.
AB  - Transcatheter closure of interatrial septal defects is guided by transesophageal
      echocardiography (TEE), which requires general anesthesia in most cases. Using a
      new intracardiac echocardiographic (ICE) catheter may avoid endotracheal and
      esophageal intubation while using only local anesthesia. Forty-two patients
      underwent transcatheter interatrial septal defect closure; half of them underwent
      TEE guidance with general anesthesia and the other half underwent ICE guidance
      with local anesthesia. Device deployment success rate, adequate 2-dimensional and
      Doppler visualization of the defect and deployment steps, interatrial
      communication closure at 24 hours, and at 3 and 6 months, procedure time length,
      complications, fluoroscopic time, and length of hospitalization were compared
      between both methods. All interventions were completed successfully with no
      complications, except for 1 patient in the TEE group who had a minor oral trauma.
      Echocardiographic visualization of the septal defect and deployment was adequate
      by both methods. Catheterization laboratory time (92 +/- 18 vs 50 +/- 12 minutes,
      p <0.001) and interventional procedure length (47 +/- 8 vs 35 +/- 6 minutes, p
      <0.001) were shortened using ICE. There was no difference in the rate of closure
      after 6-month follow-up by either method. ICE guidance offers equivalent
      echocardiographic views compared with TEE and similar rates of closure. ICE is
      associated with decreased procedure length while eliminating the risks of
      endotracheal or esophageal intubation and general anesthesia.

PMID- 14969618
TI  - Pilots, hypertrophic cardiomyopathy, and issues of aviation and public safety.

PMID- 14969619
TI  - Importance of the first two minutes of heart rate recovery after exercise
      treadmill testing in predicting mortality and the presence of coronary artery
      disease in men.
AB  - We retrospectively analyzed exercise treadmill and coronary angiographic data of
      2,193 men to compare heart rate (HR) recovery with angiographic and mortality
      data during a follow-up study of 7 +/- 2.7 years. Only the first 2 minutes of HR
      recovery predicted mortality (p <0.001), and the HR decrease during the second
      minute of recovery predicted the presence of coronary artery disease (p <0.05).

PMID- 14969620
TI  - Prediction of all-cause mortality in women with known or suspected coronary
      artery disease by stress technetium-99m tetrofosmin myocardial perfusion imaging.
AB  - We studied the incremental value of stress technetium-99m tetrofosmin imaging for
      predicting all-cause mortality in 503 women (aged 58 +/- 12 years) with known or
      suspected coronary artery disease. The annual mortality rate was 1.4% with normal
      perfusion and 4% with abnormal perfusion (p <0.01) during a follow-up of 3.5 +/-
      1.2 years. In an incremental multivariate analysis model, clinical predictors of
      mortality were age, diabetes mellitus, smoking, and a lower systolic blood
      pressure during stress. An abnormal scan was incremental to clinical data in
      predicting mortality.

PMID- 14969621
TI  - Incidence and time course of thrombocytopenia with abciximab and eptifibatide in
      patients undergoing percutaneous coronary intervention.
AB  - Thrombocytopenia is recognized as a potential adverse effect in patients treated
      with glycoprotein IIb/IIIa inhibitors. We monitored platelet counts at baseline
      and at 10 minutes and at 1, 8, and 24 hours after initiation of therapy with
      either abciximab (n = 74) or eptifibatide (n = 26) in a series of 100 consecutive
      patients who underwent percutaneous coronary intervention. Thrombocytopenia
      (platelet count <100,000 m(3) occurred in 11 patients treated with abciximab
      (15%) and in none of those treated with eptifibatide. The inhibition of platelet
      adhesion to fibrinogen-coated material by abciximab and eptifibatide was similar,
      indicating that the reduction in platelet count with abciximab is unrelated to
      inhibition of platelet function.

PMID- 14969622
TI  - Frequency of nonresponse antiplatelet activity of clopidogrel during pretreatment
      for cardiac catheterization.
AB  - Platelet function was evaluated before and after clopidogrel therapy in 50
      cardiology candidates scheduled for intervention; results were averaged from
      optical platelet aggregation with 2 significantly correlated point-of-care
      instruments, Thrombelastograph and Ichor PlateletWorks. Although this was a
      limited study with few complications, the failure of clopidogrel therapy (30%
      nonresponders with <10% average platelet inhibition) was not correlated with
      clinical pretreatment variables, including atorvastatin therapy, postintervention
      bleeding complications, or major adverse coronary events.

PMID- 14969623
TI  - Risk factors for intracranial hemorrhage and nonhemorrhagic stroke after
      fibrinolytic therapy (from the GUSTO-i trial).
AB  - Of 592 patients in the Global Utilization of Streptokinase and tPA for Occluded
      Arteries-I trial who had a stroke during initial hospitalization, the risk for
      intracranial hemorrhage was significantly greater in those with recent facial or
      head trauma (odds ratio 13.0, 95% confidence interval 3.4 to 85.5); dementia was
      additionally associated with an increased risk for intracranial hemorrhage (odds
      ratio 3.4, 95% confidence interval 1.2 to 10.2). Because facial or head trauma
      may greatly influence treatment decisions, this risk factor should be
      incorporated into models designed to estimate the risks and benefits of
      fibrinolytic therapy.

PMID- 14969624
TI  - Two-year outcomes after enhanced external counterpulsation for stable angina
      pectoris (from the International EECP Patient Registry [IEPR]).
AB  - We assessed the long-term outcomes of enhanced external counterpulsation in
      relieving angina and improving the quality of life in a large cohort of patients
      with chronic angina pectoris. Seventy-three percent had a reduction by > or =1
      angina class at the end of treatment, and 50% reported an improvement in the
      quality-of-life assessment after enhanced external counterpulsation; these
      results were sustained at 2-year follow-up.

PMID- 14969625
TI  - Effect of enhanced external counterpulsation on dobutamine-induced left
      ventricular wall motion abnormalities in severe chronic angina pectoris.
AB  - We studied the effect of enhanced external counterpulsation (EECP) in 23
      consecutive patients with stable angina pectoris who had a positive dobutamine
      stress echocardiogram. After EECP, stress-induced wall motion score (WMS)
      improved by > or =2 grades in 43% of the patients (n = 10); the average
      improvement was 5.3 +/- 3.8 compared with -0.6 +/- 3.0 in the remaining 13
      patients (p = 0.007). The diastolic/systolic augmentation ratio increased by 217%
      in response to the full course of EECP (p = 0.0002) among patients with improved
      WMS, and by 71% (p = 0.004) among the other patients; the increase was greater
      among patients with improved WMS than among patients with no improvement (p =
      0.01). After EECP, Canadian Cardiovascular Society angina class improved from 3.1
      +/- 0.6 to 2.2 +/- 0.7 (p <0.0001) in the entire group and exercise capacity
      increased by 73 seconds (p = 0.0002) in patients who were able to exercise (n =
      18).

PMID- 14969626
TI  - Effectiveness of primary angioplasty for acute myocardial infarction in patients
      on dialysis.
AB  - We sought to characterize the outcome in patients who were on long-term dialysis
      and who underwent primary percutaneous transluminal coronary angioplasty (PTCA)
      for acute myocardial infarction. Of 2,831 consecutive patients who underwent
      primary PTCA for acute myocardial infarction from 1993 to 2001, 15 patients on
      long-term dialysis were identified. This small cohort had a 40% incidence of
      cardiogenic shock on admission. Despite the angiographic success rate for primary
      PTCA of 80%, in-hospital mortality was 53%.

PMID- 14969627
TI  - Intravascular ultrasound study of effects of overlapping sirolimus-eluting
      stents.
AB  - Drug-eluting stents have been investigated as a treatment option for in-stent
      restenosis after bare metal stenting. However, it remains unclear whether
      overlapping drug-eluting stents have a toxic effect on the vessel wall. The aim
      of this study was to analyze the 1-year intravascular ultrasound findings after 2
      overlapping sirolimus-eluting stent implantations in patients with in-stent
      restenosis lesions. Eight patients required 2 sirolimus-eluting stents, 18 mm in
      length, for full lesion coverage; these stents were implanted with >1-mm overlap.
      At 1-year follow-up, there were no significant quantitative changes in
      intravascular ultrasound measurements within the overlapped segment.

PMID- 14969628
TI  - Comparison of diamond-like carbon-coated stents versus uncoated stainless steel
      stents in coronary artery disease.
AB  - Stainless steel (SS) and carbon-coated (CC) stents were randomly compared in 347
      patients (520 lesions). No differences were observed in in-hospital major adverse
      cardiac events: 2.8% in the CC group and 4.5% in the SS group (p = 0.286). The 6
      month follow-up showed similar rates of binary restenosis (31.8% in the CC group
      vs 35.9% in the SS group; p = 0.448) and of cumulative major adverse cardiac
      events (30.5% in the CC group vs 32.7% in the SS group; p = 0.675). In unselected
      patients and lesions, carbon coating does not provide significant improvements
      over SS stents with the same design.

PMID- 14969629
TI  - Impact of strut thickness on late luminal loss after coronary artery stent
      placement.
AB  - To determine the influence of coronary artery stent strut thickness on
      angiographic late luminal loss, 663 patients were included in a single-center
      observational cohort after receiving an ACS Multilink stent in a native coronary
      vessel. At 6- to 10-month follow-up, 287 patients treated with a thin-strut stent
      (50 microm) had significantly less late luminal loss than 376 patients treated
      with a thick-strut stent (> or =90 microm) (mean 0.92 +/- 0.59 vs 1.06 +/- 0.71
      mm, p = 0.011); on multivariate regression analysis, strut thickness was found to
      be an independent predictor for late luminal loss.

PMID- 14969630
TI  - Usefulness of an abnormal ankle-brachial index to predict presence of coronary
      artery disease in African-Americans.
AB  - We sought to determine the role of an abnormal ankle-brachial index (ABI) in an
      African-American population with suspected coronary artery disease (CAD) referred
      for diagnostic coronary angiography. In this population, an ABI < or =0.90
      predicted the presence of > or =3-vessel or left main CAD with a sensitivity of
      85% and specificity of 77%. However, a normal ABI did not predict absence of 1-
      or 2-vessel CAD. These results suggest that in this population, the ABI can be
      used to increase the pretest probability of severe CAD.

PMID- 14969631
TI  - Computerized QT dispersion measurement and cardiovascular mortality in male
      veterans.
AB  - We examined the prognostic value of computerized measurements of QT dispersion in
      37,579 male veterans. The results of our study showed that QT dispersion is a
      poor independent predictor of cardiovascular mortality.

PMID- 14969632
TI  - Comparison of ability to identify left atrial thrombus by three-dimensional
      tomography versus transesophageal echocardiography in patients with atrial
      fibrillation.
AB  - We sought to determine the potential use of recently introduced cardiac 3
      dimensional computed tomography as an alternative to transesophageal
      echocardiography for examination of the left atrial appendage. Our data suggest
      that computed tomography is a potential alternative for assessing the anatomy of
      the left atrial appendage and for detecting thrombi.

PMID- 14969633
TI  - Relation of coronary artery calcium to left ventricular mass in African
      Americans.
AB  - Both coronary artery calcium (CAC) deposits and increased left ventricular (LV)
      mass are important risk factors for coronary heart disease, but the relation
      between these 2 factors has rarely been studied. We examined the correlation of
      CAC and LV mass in 159 young to middle-aged African-Americans, and found that the
      average LV mass indexes were bigger in the CAC-positive groups than in CAC
      negative groups in both genders (p = 0.0004 in men; p = 0.08 in women).

PMID- 14969634
TI  - Usefulness of clinical assessment of the carotid pulse in the diagnosis of aortic
      stenosis.
AB  - In a prospective controlled study, we compared the blinded assessment of the
      carotid pulse (independent of other clinical signs) by 1 of 3 cardiologists with
      applanation tonometry on the radial and carotid pulse (time to dominant peak and
      maximum rate of rise [-dP/dt]). We studied 23 patients with significant isolated
      aortic stenosis (AS) and 23 control patients. The odds ratio of finding a slowly
      rising pulse, representing AS, compared with a finding of a
      "normal"/"indeterminate" pulse was 10.4. Radial dP/dt was significantly lower in
      the group with AS, whereas carotid dP/dt was not significantly different between
      the 2 groups.

PMID- 14969635
TI  - Effects of cardiac resynchronization therapy on myocardial blood flow measured by
      oxygen-15 water positron emission tomography in idiopathic-dilated cardiomyopathy
      and left bundle branch block.
AB  - Regional and global myocardial blood flow and coronary vascular resistance were
      determined in patients with idiopathic-dilated cardiomyopathy and left bundle
      branch block before and during cardiac resynchronization therapy (CRT) using
      oxygen-15 water positron emission tomography. The investigated parameters did not
      exhibit regional heterogeneity and were not influenced by CRT. This implies that
      the beneficial effects of CRT do not require additional oxygen demand or regional
      reallocation of oxidative metabolism.

PMID- 14969636
TI  - Prognostic usefulness of left ventricular thrombus by echocardiography in dilated
      cardiomyopathy in predicting stroke, transient ischemic attack, and death.
AB  - Echocardiograms of 290 patients with dilated cardiomyopathy (ejection fraction <
      or =35%) were reviewed for the presence of left ventricular (LV) apical
      abnormalities; outcomes of stroke and death were then correlated with the
      presence of LV thrombus. During a follow-up of 31 months, 15 patients had a
      stroke or transient ischemic attack after the index echocardiogram (5.2%).
      Patients with LV thrombus on echocardiography had a significantly higher rate of
      stroke (adjusted odds ratio 3.4, p = 0.027) than those without echocardiographic
      evidence of thrombi. There was no difference in mortality between patients with
      and without thrombus (20.9% vs 21.1%, p = 0.726).

PMID- 14969637
TI  - Respiratory symptoms secondary to aortopulmonary collateral vessels in tetralogy
      of Fallot absent pulmonary valve syndrome.
AB  - Hemodynamically significant systemic-to-pulmonary artery collaterals may
      represent an underappreciated cause of cardiorespiratory compromise in tetralogy
      of Fallot with absent pulmonary valve (TOF/APV). We retrospectively reviewed the
      angiographic, magnetic resonance imaging, operative, and autopsy reports of the
      50 patients with TOF/APV managed at our institution in the past 10 years and
      demonstrated that at least 7 of 50 patients (14%) had significant aortopulmonary
      collaterals.

PMID- 14969638
TI  - Late post-repair ventricular function in patients with origin of the left main
      coronary artery from the pulmonary trunk.
AB  - This study investigated ventricular function in postoperative patients with
      abnormal origin of the the left main coronary artery from the pulmonary trunk
      using ultrasound-based deformation imaging. Although radial left ventricular
      deformation parameters were completely normalized, longitudinal deformation
      remained abnormal.

PMID- 14969639
TI  - Cost analysis of "bridging therapy" with low-molecular-weight heparin versus
      unfractionated heparin during temporary interruption of chronic anticoagulation.
AB  - Patients on long-term anticoagulation who require interruption of therapy for
      surgery may receive "bridging therapy" with continuous-infusion unfractionated
      heparin or low-molecular-weight heparin (LMWH). We estimated the costs of
      bridging therapy with: (1) LMWH self-administered at home, (2) LMWH administered
      by a nurse to patients at home, and (3) continuous-infusion unfractionated
      heparin in the hospital. For surgeries requiring an overnight stay, bridging
      costs are estimated to be 672, 933, and 3,816 US dollars, respectively, for each
      of these strategies.

PMID- 14969640
TI  - Analysis of occurrence of venous thromboembolic disease in the four seasons.
AB  - Reports of seasonal variation of the incidence of pulmonary embolism and deep
      venous thrombosis are inconsistent as to when or if it occurs. We used data from
      the National Hospital Discharge Survey and the United States (US) Bureau of the
      Census to test for circannual variation throughout the entire US and in regions
      of the US over a period of 21 years. Pulmonary embolism, deep venous thrombosis,
      or the combination did not show seasonal variation in the US or in any region of
      the US, including the Southern region, where winters are mild, and the
      northeastern and midwestern regions, where seasons are sharply defined.

PMID- 14969641
TI  - Analysis of infective endarteritis in patent ductus arteriosus.
AB  - This study reports on infective endarteritis in 14 children with patent ductus
      arteriosus over a period of 6 years. Infective endarteritis mostly involved the
      small ducts and was previously undiagnosed. These patients were given antibiotic
      treatment for a variable period of 4 to 10 weeks, and all except 1 underwent
      subsequent closure.

PMID- 14969642
TI  - "Read Guyton".
AB  - During my medical school years, I became acquainted with Dr. Guyton's physiology
      textbook. This book was very instrumental in shaping my future career in
      cardiovascular medicine.

PMID- 14969643
TI  - Electrocardiographic changes associated with training and discontinuation of
      training in an athlete with hypertrophic cardiomyopathy.
AB  - The 12-lead electrocardiogram of a 17-year-old African professional soccer player
      had signs of left ventricular (LV) hypertrophy and deeply inverted T waves in the
      inferior and precordial leads. Two-dimensional echocardiography showed mild LV
      hypertrophy with normal cavity size consistent with nonobstructive hypertrophic
      cardiomyopathy. After 5 months of complete discontinuation of training, the
      electrocardiogram normalized; however, the echocardiogram was unchanged.
      Subsequently, and contrary to our advice, the athlete resumed training and
      professional soccer. One year later the electrocardiogram again showed a similar
      and markedly abnormal pattern without cardiac dimensional changes.

PMID- 14969645
TI  - A propensity analysis of the impact of platelet glycoprotein IIb/IIIa inhibitor
      therapy on in-hospital outcomes after percutaneous coronary intervention.

PMID- 14969646
TI  - Congenital bicuspid aortic valve and rate of ascending aortic dilatation.

PMID- 14969647
TI  - Effectiveness of statin titration on low-density lipoprotein cholesterol goal
      attainment in patients at high risk of atherogenic events.

PMID- 14969648
TI  - Routine use of cerebral protection during carotid artery stenting: results of a
      multicenter registry of 753 patients.
AB  - PURPOSE: To evaluate the short-term outcome of patients who underwent carotid
      stenting with the routine use of cerebral protection devices. METHODS: In five
      centers, 808 successful stent procedures (of 815 attempted) were performed in 753
      patients (557 [74%] men; mean [+/- SD] age, 70 +/- 8 years). Cerebral protection
      involved distal filter devices (n=640), occlusive distal balloons (n=144), or
      proximal balloon protection (n=24). RESULTS: The protection device was positioned
      successfully in 793 (98.2%) of the 808 attempted vessels. Neurologic
      complications occurred within 30 days after 46 procedures (5.6%), including seven
      major strokes, 17 minor strokes, and 22 transient ischemic attacks. There were
      four deaths (one following a major stroke). The 30-day incidence of stroke and
      death was 3.3% (27/815). The rate of stroke or death was 3.8% (8/213) for
      symptomatic lesions and 3.2% (19/602) for asymptomatic lesions (P=0.87), and 3.4%
      (25/729) in patients aged <80 years and 2% (2/86) in those aged > or =80 years
      (P=0.81). Protection device-related vascular complications, none of which led to
      neurologic symptoms, occurred after nine procedures (1.1%). CONCLUSION: In this
      uncontrolled study, routine cerebral protection during carotid artery stenting
      was technically feasible and clinically safe. The incidence of major neurologic
      complications in this study was lower than in previous reports of carotid artery
      stenting without cerebral protection.

PMID- 14969649
TI  - Glycemic control with glyburide/metformin tablets in combination with
      rosiglitazone in patients with type 2 diabetes: a randomized, double-blind trial.
AB  - PURPOSE: To assess the efficacy and safety of adding rosiglitazone to an
      established regimen of glyburide/metformin in patients with type 2 diabetes who
      had not achieved adequate glycemic control (glycosylated hemoglobin [HbA1C]
      levels >7.0% and < or =10.0%). METHODS: Following an open-label, lead-in phase to
      optimize the dosing of glyburide/metformin tablets, 365 patients randomly
      received additive therapy comprising rosiglitazone (4 mg once daily) or placebo
      for 24 weeks. Based on glycemic response, rosiglitazone dose was maintained or
      increased to 4 mg twice daily. Glyburide/metformin dose was maintained or reduced
      by 2.5/500 mg for symptomatic hypoglycemia. The primary endpoint was the change
      in HbA1C level from baseline to week 24. The proportions of patients achieving
      HbA1C levels <7% and a fasting plasma glucose level <126 mg/dL were also
      assessed. RESULTS: After 24 weeks, therapy with glyburide/metformin plus
      rosiglitazone resulted in a greater reduction in HbA1C levels (-1.0%, P<0.001)
      compared with combination therapy that included placebo, and in a larger
      proportion of patients (42% vs. 14%) who attained levels <7%. The difference in
      fasting plasma glucose levels between groups was -48 mg/dL (P<0.001), favoring
      glyburide/metformin plus rosiglitazone. The adverse event profile in the
      rosiglitazone-treated group included mild-to-moderate edema (8%), hypoglycemia
      (22%), and weight gain of 3 kg. No patient experienced hypoglycemia requiring
      third-party assistance. CONCLUSION: In patients with inadequate glycemic control
      despite established glyburide/metformin therapy, the addition of rosiglitazone
      improves glycemic control, allowing more patients to achieve an HbA1C level <7%
      and perhaps delaying the need for insulin treatment.

PMID- 14969650
TI  - Addition of pioglitazone or bedtime insulin to maximal doses of sulfonylurea and
      metformin in type 2 diabetes patients with poor glucose control: a prospective,
      randomized trial.
AB  - PURPOSE: To compare the efficacy of adding pioglitazone or bedtime isophane (NPH)
      insulin to maximal doses of metformin and an insulin secretagogue in patients
      with poor glucose control. METHODS: We conducted a nonblinded, open-label,
      randomized controlled trial involving 62 patients with type 2 diabetes and
      glycosylated hemoglobin (HbA1C) levels >8.0%. Patients received either
      pioglitazone or bedtime NPH insulin in addition to their usual diabetes
      medication for 16 weeks. Outcome measurements of glycemic control, hypoglycemia,
      blood pressure, lipid levels, microalbuminuria, and quality of life were assessed
      at baseline and at 16 weeks. RESULTS: HbA1C levels were lowered to a similar
      degree in each treatment arm (pioglitazone: -1.9% +/- 1.5%; insulin: -2.3% +/-
      1.5%; P = 0.32), but hypoglycemia was less common among patients who received
      pioglitazone than those who received insulin (37% [11/30] vs. 68% [19/28],
      P=0.02). Pioglitazone, but not insulin, resulted in an increase in high-density
      lipoprotein (HDL) cholesterol levels. Both treatments had similar effects on
      weight, other lipid values, blood pressure, and urine microalbumin levels.
      CONCLUSION: Adding pioglitazone or bedtime insulin for 16 weeks improved glycemic
      control in type 2 diabetic patients with secondary oral agent failure.
      Pioglitazone was associated with less hypoglycemia and improved HDL cholesterol
      levels.

PMID- 14969651
TI  - Effect of type 2 diabetes and its duration on the risk of peripheral arterial
      disease among men.
AB  - PURPOSE: To assess the relation between the duration of diabetes and the risk of
      peripheral arterial disease among men. METHODS: A total of 48,607 men in the
      Health Professionals Follow-up Study who returned a questionnaire in 1986 were
      followed for 12 years. Peripheral arterial disease (intermittent claudication or
      surgery for peripheral arterial diseases in the lower extremities) was
      ascertained by biennial questionnaire and confirmed by medical record review.
      Diabetes status and other cardiovascular risk factors were also ascertained by
      biennial questionnaire. RESULTS: During follow-up (534,588 person-years), we
      documented 387 cases of peripheral arterial disease. After adjusting for
      cardiovascular risk factors, the relative risk of developing peripheral arterial
      disease among men with diabetes compared with men without diabetes was 2.61 (95%
      confidence interval [CI]: 1.98 to 3.45). Compared with men without diabetes, the
      relative risk of peripheral arterial disease among men with diabetes increased
      with duration of disease, even after adjusting for cardiovascular risk factors:
      1.39 (95% CI: 0.82 to 2.36) for 1 to 5 years of diabetes, 3.63 (95% CI: 2.23 to
      5.88) for 6 to 10 years, 2.55 (95% CI: 1.50 to 4.32) for 11 to 25 years, and 4.53
      (95% CI: 2.39 to 8.58) for >25 years of diabetes (P for trend < or =0.0001).
      CONCLUSION: These results indicate that duration of type 2 diabetes is associated
      strongly with the risk of developing peripheral arterial disease.

PMID- 14969652
TI  - Effects of sustained audit/feedback on self-reported health status of primary
      care patients.
AB  - PURPOSE: Because limited audit/feedback of health status information has yielded
      mixed results, we evaluated the effects of a sustained program of audit/feedback
      on patient health and satisfaction. METHODS: We conducted a group-randomized
      effectiveness trial in which firms within Veterans Administration general
      internal medicine clinics served as units of randomization, intervention, and
      analysis. Respondents to a baseline health inventory were regularly mailed the 36
      Item Short Form (SF-36) and, as relevant, questionnaires about six chronic
      conditions (ischemic heart disease, diabetes, chronic obstructive pulmonary
      disease, depression, alcohol use, and hypertension) and satisfaction with care.
      Data were reported to primary providers at individual patient visits and in
      aggregate during a 2-year period. RESULTS: Baseline forms were mailed to 34,050
      patients; of the 22,413 respondents, 15,346 completed and returned follow-up
      surveys. Over the 2-year study, the difference between intervention and control
      groups (as measured by difference in average slope) was -0.26 (95% confidence
      interval [CI]: -0.79 to 0.27; P=0.28) for the SF-36 Physical Component Summary
      score and -0.53 (95% CI: -1.09 to 0.03; P=0.06) for the SF-36 Mental Component
      Summary score. No significant differences emerged after adjusting for deaths.
      There were no significant differences in condition-specific measures or
      satisfaction between groups after adjustment for provider type, panel size, and
      number of intervention visits, or after analysis of patients who completed all
      forms. CONCLUSION: An elaborate, sustained audit/feedback program of general and
      condition-specific measures of health/satisfaction did not improve outcomes. To
      be effective, such data probably should be incorporated into a comprehensive
      chronic disease management program.

PMID- 14969653
TI  - Interpretations of 'appropriate' minority inclusion in clinical research.
AB  - The range of possible interpretations of the phrase "appropriate representation"
      has left investigators struggling with the practical application of the National
      Institutes of Health guidelines on the inclusion of minorities in research. At
      least three goals might be reached by including minorities in clinical research:
      to test specific hypotheses about differences by race and ethnicity; to generate
      hypotheses about possible differences by race and ethnicity; and to ensure the
      just distribution of the benefits and burdens of participation in research,
      regardless of whether there are expected differences in outcome by race or
      ethnicity. In this paper, we describe possible interpretations of "appropriate
      representation," as well as provide a general approach that investigators might
      use to address this issue. To expand scientific knowledge about the health of
      minority populations, investigators should be expected to state which goal they
      have selected and why that goal is appropriate as compared with other possible
      goals.

PMID- 14969654
TI  - Clinical outcomes of primary stenting versus balloon angioplasty in patients with
      myocardial infarction: a meta-analysis of randomized controlled trials.
AB  - PURPOSE: To examine whether primary stenting as compared with primary balloon
      angioplasty reduces clinical outcomes in patients with myocardial infarction.
      METHODS: Major medical databases from 1979 to March 2002 were searched for
      randomized controlled trials that compared primary stenting with balloon
      angioplasty in patients with myocardial infarction. Two independent reviewers
      selected and extracted data from identified trials. The outcomes were mortality
      at 30 days, 6 months, and 12 months; recurrent events; and bleeding. RESULTS:
      Nine trials with a total of 4433 patients fulfilled the inclusion criteria. The
      odds ratios for mortality after stenting as compared with balloon angioplasty
      were 1.17 (95% confidence interval [CI]: 0.78 to 1.74) at 30 days, 1.07 (95% CI:
      0.76 to 1.52) at 6 months, and 1.09 (95% CI: 0.80 to 1.50) at 12 months (P for
      heterogeneity >0.1 for each comparison). The odds ratios for reinfarction after
      stenting as compared with balloon angioplasty were 0.52 (95% CI: 0.31 to 0.87) at
      30 days, 0.67 (95% CI: 0.45 to 1.00) at 6 months, and 0.67 (95% CI: 0.45 to 0.99)
      at 12 months; for target vessel revascularization, they were 0.46 (95% CI: 0.34
      to 0.61) at 30 days, 0.42 (95% CI: 0.35 to 0.51) at 6 months, and 0.48 (95% CI:
      0.39 to 0.59) at 12 months (P for heterogeneity >0.1 for all estimates with the
      exception of reinfarction at 12 months where P=0.08). The odds ratio for
      postinterventional bleeding complications after stenting as compared with balloon
      angioplasty was 1.34 (95% CI: 0.95 to 1.88; P for heterogeneity >0.1).
      CONCLUSION: Compared with balloon angioplasty, primary stenting is not associated
      with lower mortality, but is associated with a lower risk of reinfarction and
      target vessel revascularization.

PMID- 14969655
TI  - The renin-angiotensin-aldosterone system and the kidney: effects on kidney
      disease.
AB  - The renin-angiotensin-aldosterone system regulates renal vasomotor activity,
      maintains optimal salt and water homeostasis, and controls tissue growth in the
      kidney. However, pathologic consequences can result from overactivity of this
      cascade, involving it in the pathophysiology of kidney disease. An activated
      renin-angiotensin-aldosterone system promotes both systemic and glomerular
      capillary hypertension, which can induce hemodynamic injury to the vascular
      endothelium and glomerulus. In addition, direct profibrotic and proinflammatory
      actions of angiotensin II and aldosterone may also promote kidney damage. The
      majority of the untoward effects associated with angiotensin II appear to be
      mediated through its binding to the angiotensin II type 1 receptor. Aldosterone
      can also induce renal injury by binding to its receptor in the kidney. An
      understanding of this system is important to appreciate that inhibitors of this
      cascade can reduce the progression of chronic kidney disease in proteinuric
      disease states. Pharmacologic agents that can interfere with this cascade include
      angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and
      aldosterone receptor antagonists. This paper will provide an overview of the
      renin-angiotensin system, review its role in kidney disease, examine the renal
      effects of inhibition of this cascade in experimental animal models, and review
      clinical studies utilizing renin-angiotensin-aldosterone inhibitors in patients
      with diabetic and nondiabetic nephropathies.

PMID- 14969656
TI  - Carotid artery stenting--evolution of a technique to rival carotid
      endarterectomy.

PMID- 14969657
TI  - What to do when two oral agents fail to control type 2 diabetes--a matter of
      opinion or a matter of fact?

PMID- 14969658
TI  - How stressful can it be to catch a thief? The influence of stress on calcium
      metabolism.

PMID- 14969659
TI  - Low erythropoietin level can cause anemia in patients without advanced renal
      failure.

PMID- 14969660
TI  - Topiramate-induced renal tubular acidosis.

PMID- 14969661
TI  - Severe acute myopathy induced by minocycline.

PMID- 14969662
TI  - The case for diversity in academic internal medicine.

PMID- 14969663
TI  - Presenting health risks honestly: mifepristone, a case in point.

PMID- 14969664
TI  - A 3-year double-blind, randomized, controlled study on the influence of two oral
      contraceptives containing either 20 microg or 30 microg ethinylestradiol in
      combination with levonorgestrel on bone mineral density.
AB  - In this first prospective, double-blind, randomized, parallel-group study we
      evaluated the influence of two combined oral contraceptives on bone mineral
      density (BMD) and metabolic bone parameters. One dose-reduced preparation
      contained 20 microg ethinylestradiol (EE) in combination with 100 microg
      levonorgestrel (LNG) (20/100) was compared with the reference preparation which
      contained 30 microg EE in combination with 150 microg LNG (30/150). Data from 48
      volunteers aged 20-35 years were obtained over an observation period of 36
      treatment cycles. The direction of the change (increase or decrease) in all
      investigated bone-related variables was similar in both treatment groups. As
      compared to baseline, bone mineral density decreased by 0.4% in the 20/100 group
      and by 0.8% in the 30/150 group after 36 treatment cycles. These changes were not
      significantly different between the two treatment groups (p = 0.902). For bone
      specific alkaline phosphatase, we measured a mean increase of 55.4% (20/100
      group) and of 113.2% (30/150 group) after 36 treatment cycles. The two treatments
      did not differ statistically significantly (p = 0.522). With respect to cross
      linked N-telopeptides (NTx), we detected a decrease of the mean NTx urine
      concentrations of 21.1% (20/100) and of 13.4% (30/150). These changes also did
      not significantly differ between the two treatments (p = 0.613). Both study
      treatments were safe and well-tolerated by all volunteers participating in the
      study. In conclusion, BMD did not change during the 3-year observation period.
      Thus, both trial preparations containing either 20 or 30 microg EE in combination
      with LNG were capable of maintaining BMD in young fertile women. There is no
      reason to assume that the EE dose reduction had any negative impact on BMD.
      Because there were no differences in BMD between the treatment groups, it can be
      assumed that even lower dosages than 20 microg EE might be sufficient for bone
      protection. Biochemical markers provided evidence for a reduced bone resorption.

PMID- 14969665
TI  - The impact of improved compliance with a weekly contraceptive transdermal system
      (Ortho Evra) on contraceptive efficacy.
AB  - OBJECTIVE: The contraceptive efficacy of perfect dosing cycles and imperfect
      dosing cycles has not been described previously. Method compliance determines the
      proportion of perfect and imperfect dosing cycles, and together can form the
      basis for evaluating differences in efficacy based on differences in compliance.
      MATERIALS AND METHODS: The transdermal contraceptive delivery system (Ortho Evra)
      has been studied in a North American randomized trial vs. an oral contraceptive
      (OC) and in total has been evaluated in 3319 women in contraceptive clinical
      trials. This article explores the impact of perfect vs. imperfect compliance with
      the contraceptive method on contraceptive efficacy. Previously published data for
      a transdermal system (Patch, n = 812) and OC (Triphasil, n = 605) users from the
      North American comparative study were reanalyzed to determine the effect of
      imperfect use on the contraceptive efficacy of the different methods. RESULTS:
      Contraceptive efficacy was significantly better (p = 0.007) in cycles with
      perfect dosing (Pearl Index = 0.83) compared to those with imperfect dosing
      (Pearl Index = 6.32) for both methods. This difference is homogeneous (p = 0.62)
      across the Patch and OC groups. Pooled data for all Patch users confirm that
      perfect dosing cycles are associated with significantly better efficacy than
      imperfect dosing cycles (p = 0.047). In addition, compliance did not vary by age
      in the pooled Patch data, which are in agreement with the previously published
      Patch data from the comparative study. In the comparative study, the percentage
      of cycles with perfect dosing was significantly higher with the Patch than with
      the OC (88.7% vs. 79.2%, p < 0.001), and was consistently high in all age groups
      (range, 89.6-91.8%). By contrast, among OC users, the percentage of cycles with
      perfect dosing increased with increasing age (p < 0.001) from 67.7% in users aged
      18-20 years to more than 80% in those aged 30 years and older. CONCLUSION: In
      conclusion, deviations from perfect use (whether corrected or not) of a
      transdermal contraceptive system and of an OC increase contraceptive failures by
      approximately 5-10-fold when compared to perfect use. The weekly change schedule
      of the transdermal contraceptive delivery system is associated with a
      significantly greater proportion of cycles in which there is perfect dosing
      compared to an OC.

PMID- 14969666
TI  - The combined contraceptive vaginal ring, NuvaRing, and tampon co-usage.
AB  - We investigated the effect of tampon co-usage on systemic exposure to
      etonogestrel (ENG) and ethinylestradiol (EE) from the combined contraceptive
      vaginal ring, NuvaRing. One cycle of ring use consists of 3 weeks of ring use
      followed by a 1-week ring-free period. Fourteen healthy women were randomized to
      use both NuvaRing and tampons (Kotex( regular) or NuvaRing alone for one cycle;
      participants then switched to the alternate treatment regimen for a second cycle
      of ring use. The first tampon was self-administered on day 8 of the interaction
      cycle; 4 tampons a day were used for 3 consecutive days. Tampon co-usage did not
      result in any changes in serum ENG or EE concentrations and is thus not expected
      to compromise the ring's contraceptive efficacy.

PMID- 14969667
TI  - The importance of screening and monitoring: the Standard Days Method and cycle
      regularity.
AB  - The Standard Days Method is a simple fertility awareness-based method of family
      planning with a correct-use pregnancy rate of 4.8 at 1 year and a typical-use
      pregnancy rate of 12. The protocol for providing the method includes guidelines
      for screening potential users for cycle regularity. There also are guidelines for
      monitoring users to determine continued method eligibility. This article explores
      the importance of these screening and monitoring procedures. A large existing
      dataset from a World Health Organization study of the Ovulation Method was used
      to estimate the theoretical probability of pregnancy using the Standard Days
      Method, with and without screening and monitoring. We used data from the efficacy
      study of the Standard Days Method to examine the effectiveness of current
      screening and monitoring procedures. Results suggest that current screening and
      monitoring procedures are useful in identifying women for whom the Standard Days
      Method is less effective. Strict adherence to these procedures is ideal, but even
      women who do not meet the cycle-regularity guidelines would have a relatively low
      probability of pregnancy.

PMID- 14969668
TI  - Three-year efficacy and acceptability of the GyneFix 200 intrauterine system.
AB  - OBJECTIVE: This study was conducted to evaluate the efficacy of a "mini" version
      of the frameless intrauterine system (IUS; GyneFix), which has a copper surface
      area of approximately 200 mm(2). The small GyneFix version consists of four
      copper cylinders instead of six and is only 2 cm long. MATERIALS AND METHODS: A
      total of 392 insertions were performed in an open nonrandomized study in parous
      (76%) and nulligravid/nulliparous (24%) women in Belgium and China. This interim
      analysis reports on 13,699 women-months of use. All women were followed-up for a
      minimum of 12 months, up to 3 years and longer. RESULTS: Four pregnancies
      occurred with the GyneFix 200 IUS in this study, of which one occurred after
      unnoticed expulsion of the device, yielding a cumulative failure rate of 0.48 at
      3 years. The cumulative removal rate for medical reasons was 1.65 at 3 years and
      the expulsion rate was 0.39. These low event rates resulted in a high
      continuation of use (93.92 at 3 years). Neither perforations nor pelvic
      inflammatory disease cases were encountered in this study. CONCLUSION: The
      present study suggests that the GyneFix 200 IUS is highly effective and probably
      as effective as the standard GyneFix IUS. This is attributed to the anchoring of
      the device to the fundus of the uterus, promoting its contraceptive action. The
      total surface area of the device, releasing a maximum amount of copper ions, is
      the fundamental difference between it and conventional IUDs and is probably
      essential in obtaining the high contraceptive efficacy seen in this study. The
      small total surface area of the GyneFix 200 IUS also minimizes menstrual bleeding
      and is an improvement over larger types of conventional IUDs, as indicated by the
      low removal rate for abnormal bleeding with the small GyneFix.

PMID- 14969669
TI  - Applying motivational interviewing to contraceptive counseling: ESP for
      clinicians.
AB  - Healthcare providers are in a unique position to address women's risk of
      unintended pregnancy and sexually transmitted infections (STIs), yet evidence for
      effective counseling strategies is limited. One approach to developing effective
      contraceptive counseling methods may be the application of theory-based behavior
      counseling models. One such model, motivational interviewing (MI), is a promising
      approach for addressing risk-taking behaviors of many kinds. We propose
      application of MI to contraceptive counseling. This process, ESP, involves
      Exploring discrepancies between pregnancy intention and contraceptive use and
      between risk of STIs and condom use, Sharing information and Promoting behaviors
      to reduce risk. This model emphasizes the importance of identifying discrepancies
      between goals and behaviors and supporting women's confidence in using
      appropriate contraceptive methods

PMID- 14969670
TI  - Sociocultural and religious influences on the normative contraceptive practices
      of Latino women in the United States.
AB  - Presumably, Latino women engage in little family planning because of religious or
      cultural objections to contraception. The purpose of this study was to examine
      how acculturation, religion and various demographic factors were related to the
      family-planning behaviors of Latino women in the United States. Data were
      collected on 234 pregnant women (aged 18-40 years), on their family size, how
      actively they planned their current pregnancy, and how consistently they used
      contraception in the past. Through path analysis, we found that Spanish-speaking
      women were more consistent contraceptive users than their English-speaking
      counterparts, suggesting that acculturation negatively impacts contraceptive use.
      However, Spanish-speaking women with longer US residency were more likely to be
      consistent contraceptive users than Spanish-speaking women who had lived in the
      United States for briefer periods, suggesting a positive effect of acculturation.
      Religiosity and years of education were associated with family size, but not
      contraceptive use. Women who were married and had fewer children were more likely
      to plan their current pregnancy, indicating that Latino women take family size
      and marital status into consideration when actively deciding to become pregnant.

PMID- 14969671
TI  - The role of misconceptions on Latino women's acceptance of emergency
      contraceptive pills.
AB  - The goal of this study was to assess factors associated with hormonal emergency
      contraception (EC) awareness and acceptability among a sample of low-income
      Latino women receiving care in two university reproductive health clinics. A
      total of 297 Latino women, 18-43 years of age, completed a survey about EC
      awareness during a clinic visit, between January and May 2003. Those women with
      some degree of awareness (n = 73) also completed questions related to their
      acceptance of EC. Factors examined included language preference, demographic
      characteristics, pregnancy history, contraceptive use history and knowledge and
      concerns about EC usage. We found that only 41% of English-speaking and 17% of
      Spanish-speaking women had ever heard of EC [adjusted odds ratio (OR) = 2.9,
      confidence interval (CI): 1.3, 6.4]. Among those aware of EC, unwillingness to
      use this method was associated with low levels of knowledge about the EC
      mechanism of action, but not about the EC regimen (adjusted OR = 0.5; CI: 0.3,
      0.9). Specific misconceptions underlying their objections included the belief
      that women are more likely to get pregnant in the beginning of their cycle
      compared to the middle (unadjusted OR = 6.3; CI: 1.8, 22.6), and a belief that EC
      prevents implantation rather than ovulation (unadjusted OR = 5.7; CI: 1.2, 28.1).
      The extent to which the women considered EC to be morally wrong depended on their
      misconceptions about the EC mechanism, not on their religious background. The
      link between expressed moral concerns and incorrect knowledge coupled with its
      lack of association to religiosity suggests that enhanced education can help to
      alleviate moral objections, thereby increasing potential usage of EC to prevent
      unintended pregnancy.

PMID- 14969672
TI  - Sexual behavior of women taking low-dose oral contraceptive containing 15 microg
      ethinylestradiol/60 microg gestodene.
AB  - The objective of this prospective study was to assess the effects of a low-dose
      oral contraceptive (OC) containing 15 microg ethinylestradiol and 60 microg
      gestodene on sexuality. Forty-eight healthy volunteers (age range, 18-35 years),
      having regular menstrual cycles with ovulation, participated in the study. Sexual
      behavior was assessed using the self-administered Personal Experience
      Questionnaire, at baseline, and at 3, 6 and 9 months of pill use. Women reported
      decreased sexual desire (p < 0.005) and sexual activity (p < 0.05) at the 9th
      month of pill use, and diminished sexual arousal at the 3rd month of pill intake
      (p < 0.05), with respect to baseline. The frequency of orgasm did not change
      during OC use (p = NS). Moreover, sexual enjoyment was worse at the 3rd, 6th and
      9th month with respect to baseline (p < 0.001). The low dose of ethinylestradiol
      could cause decreased vaginal lubrication, and diminished sexual arousal could be
      due to hypoandrogenism. Women may expect increased sexual performance when they
      take the pill, as compared to before starting contraception. Consequently, they
      could have an unexpected effect with pill use, though sexuality may remain the
      same.

PMID- 14969673
TI  - Failure of family-planning referral and high interest in advanced provision
      emergency contraception among women contacted for STD partner notification.
AB  - BACKGROUND: Few data are available on the risk of unintended pregnancy in women
      with STD or how contraceptive services can be integrated into STD control
      activities. OBJECTIVE: To define the risk for unintended pregnancy and assess the
      effectiveness of family-planning (FP) referral and interest in advanced provision
      emergency contraception (APEC) among women with gonorrhea or chlamydial
      infection. METHODS: Female participants in a randomized trial of different
      approaches to partner notification were interviewed, offered referral for FP
      services and asked if they would want APEC. RESULTS: Among participants ages 14
      24, the observed past pregnancy rate and age-adjusted anticipated past pregnancy
      rate were, respectively, 196 and 72 per 1000 women-years. Of 474 nonpregnant
      participants who did not desire pregnancy, 127 (34%) were using no contraception
      or condoms alone, of whom 8 (6%) requested a FP appointment and 81% wanted APEC.
      CONCLUSIONS: Women treated for STD are at high-risk for unintended pregnancy.
      Although referral for FP was ineffective, interest in APEC was very high.

PMID- 14969674
TI  - A pilot study on the acceptability of levonorgestrel-releasing intrauterine
      device by young, single, nulliparous Chinese females following surgical abortion.
AB  - This study investigated the acceptability of the levonorgestrel-releasing
      intrauterine device (LNG-IUS) as contraception among young, single women after
      termination of pregnancy. Twenty subjects, with a median age of 21 years, had LNG
      IUS inserted immediately after suction termination of first-trimester pregnancy.
      The subjects were followed-up at 6 weeks, 3 months, 6 months and 12 months.
      Fifteen subjects (75%) had other pregnancies terminated in the past. There were
      no serious complications or pregnancies. The acceptability of the LNG-IUS was
      generally above 86% during each follow-up visit. A total of seven (35%) subjects
      were lost to follow-up at different periods of the study. Overall, four subjects
      (22%) had the LNG-IUS removed. Nine subjects were seen at the end of the 1-year
      study period and all continued with the LNG-IUS for contraception. Side effects
      were commonly observed and irregular vaginal bleeding was the most common. We
      conclude that the LNG-IUS may be an acceptable method among selective young,
      single, nulliparous clients after termination of pregnancy and could be offered
      as an option of contraception to them. However, the small sample size and the
      high lost-to-follow-up rate are the major limitations of this study.

PMID- 14969675
TI  - Oral contraceptive use and risk of diabetes among Chinese women.
AB  - Oral contraceptive (OC) use has been associated with alterations in carbohydrate
      metabolism. We examined the effect of OC use on the risk of diabetes among
      Chinese women. A nested case-control study was conducted among 57,130 women
      screened for diabetes at enrollment for the Shanghai Women's Health Study, a
      population-based cohort study of Chinese women aged 40-70 years in Shanghai,
      China. Included in this study were 259 women newly diagnosed with diabetes and
      2072 age-matched controls (8 controls per case), randomly selected from women who
      tested negative for urine glucose. Multivariate-adjusted odds ratios (OR) and 95%
      confidence intervals (CI) were used to measure the strength of the association
      between OC use and diabetes risk. Overall, OC use was not associated with the
      risk of diabetes. Stratified analysis by menopausal status revealed a dose
      response relationship between the duration of OC use and the risk of diabetes
      among premenopausal women (p for trend = 0.02), with a 3.2-fold elevated risk
      observed among those who used OC longer than 1 year. Risk of diabetes diminished
      with increasing time since last OC use (p = 0.02). Use of intrauterine devices
      was associated with a reduced risk of diabetes in both pre- and postmenopausal
      women (OR = 0.67, CI: 0.48-0.93). These findings suggest that recent use (within
      5 years) and continued use (>1 year) of OCs may increase the risk of diabetes
      among Chinese women. However, the attributable risk for diabetes among OC users
      in the general population, if confirmed by further studies, appears to be small.

PMID- 14969676
TI  - Problems in the conduct and analysis of "A comparative randomized study of three
      different IUDs in nulliparous Mexican women".

PMID- 14969677
TI  - Cryopreservation of protozoan parasites.
AB  - Conventional methods for the propagation and preservation of parasites in vivo or
      in vitro have some limitations, including the need for labor, initial isolation
      and loss of strains, bacterial, and fungal contamination, and changes in the
      original biological and metabolic characteristics. All these disadvantages are
      considerably reduced by cryopreservation. In this study, we examined the effects
      of various freezing conditions on the survival of several protozoan parasites
      after cryopreservation. The viability of Entamoeba histolytica was improved by
      seeding (p < 0.05, chi2 test), while this was not so effective for Trichomonas
      vaginalis. Of six cryoprotectants examined, dimethyl sulfoxide (Me(2)SO), and
      glycerol showed the strongest cryoprotective effects. The optimum conditions for
      using Me(2)SO were a concentration of 10% with no equilibration, and those for
      glycerol were a concentration of 15% with equilibration for 2h. The optimum
      cooling rate depended on the parasite species. Trypanosoma brucei gambiense and
      Leishmania amazonensis were successfully cryopreserved over a wide range of
      cooling rates, whereas the survival rates of E. histolytica, T. vaginalis,
      Pentatrichomonas hominis, and Blastocystis hominis were remarkably decreased when
      frozen at improper rates. Unlike the cooling rate, exposure of the protozoans to
      a rapid thawing method produced better motility for all parasites.

PMID- 14969678
TI  - Direct cell injury associated with eutectic crystallization during freezing.
AB  - Freezing induced direct cell injury has been explained by a two-factor hypothesis
      intracellular ice formation (IIF) at rapid cooling rates, and solution effects at
      slow cooling rates. Even though IIF is generally believed to be a major injury
      mechanism at rapid cooling rates, injury by solution effects is not fully
      understood and several injury mechanisms have been suggested. Solution effects
      have generally been considered the result of the elevated electrolyte
      concentration within the intracellular and extracellular space during freezing.
      In addition to the injury by this elevated electrolyte concentration, freezing
      injury associated with eutectic crystallization was investigated. To examine the
      injury associated with eutectic crystallization, two different experiments were
      designed and performed. In the first experiment, two groups of AT-1 rat prostate
      tumor cell suspensions were frozen and thawed on a cryomicroscope in the same way
      except that eutectic crystallization was initiated in only one group. During the
      second experiment, AT-1 cells were suspended in several different media, which
      have different eutectic crystallization temperatures, and exposed to a single
      cooling-warming cycle with varying end temperature of the protocol on a
      directional solidification stage. After both experiments, post-thaw viability was
      evaluated and compared. The post-thaw viability drops significantly upon the
      occurrence of the eutectic crystallization regardless of suspending media, which
      suggests direct cell injury associated with eutectic crystallization. Based on
      these observations, two possible injury mechanisms are anticipated: (i)
      mechanical damage to the cell membrane due to eutectic crystallization, and (ii)
      intracellular eutectic formation (IEF). The proposed mechanisms provide a more
      comprehensive physical explanation of freezing induced cell injury and extend the
      understanding on solution effects.

PMID- 14969679
TI  - Improved vitrification solutions based on the predictability of vitrification
      solution toxicity.
AB  - Long-term preservation of complex engineered tissues and organs at cryogenic
      temperatures in the absence of ice has been prevented to date by the difficulty
      of discovering combinations of cryoprotectants that are both sufficiently non
      toxic and sufficiently stable to allow viability to be maintained and ice
      formation to be avoided during slow cooling to the glass transition temperature
      and subsequent slow rewarming. A new theory of the origin of non-specific
      cryoprotectant toxicity was shown to account, in a rabbit renal cortical slice
      model, for the toxicities of 20 vitrification solutions and to permit the design
      of new solutions that are dramatically less toxic than previously known solutions
      for diverse biological systems. Unfertilized mouse ova vitrified with one of the
      new solutions were successfully fertilized and regained 80% of the absolute
      control (untreated) rate of development to blastocysts, whereas ova vitrified in
      VSDP, the best previous solution, developed to blastocysts at a rate only 30% of
      that of controls. Whole rabbit kidneys perfused at -3 degrees C with another new
      solution at a concentration of cryoprotectant (8.4M) that was previously 100%
      lethal at this temperature exhibited no damage after transplantation and
      immediate contralateral nephrectomy. It appears that cryoprotectant solutions
      that are composed to be at the minimum concentrations needed for vitrification at
      moderate cooling rates are toxic in direct proportion to the average strength of
      water hydrogen bonding by the polar groups on the permeating cryoprotectants in
      the solution. Vitrification solutions that are based on minimal perturbation of
      intracellular water appear to be superior and provide new hope that the
      successful vitrification of natural organs as well as tissue engineered or
      clonally produced organ and tissue replacements can be achieved.

PMID- 14969680
TI  - Effect of cholesterol-loaded cyclodextrin on the cryosurvival of bull sperm.
AB  - Bull sperm were treated with several levels of cholesterol-loaded cyclodextrin
      (CLC) and frozen in egg yolk diluents containing either Tris or sodium citrate,
      to determine the CLC concentration that best benefits bull sperm cryosurvival.
      After thawing, higher percentages of motile (60%) and viable (55%) sperm were
      obtained when 1.5mg/ml CLC was added to sperm prior to freezing, than for sperm
      frozen in egg yolk Tris alone (42 and 46%, respectively; P < 0.05). Increasing
      concentration of CLCs, maintained higher percentages of viable sperm up to
      addition of 6.0mg/ml CLC when the percentages of viable sperm began to decline
      (50%; P < 0.05). Addition of 1.5mg/ml CLC to sperm frozen in sodium citrate
      diluent resulted in 53% motile sperm compared to 37% for control, although these
      were not different (P > 0.05). The beneficial effects of CLC addition were
      observed regardless of whether sperm incubated with CLC at 22 or 37 degrees C (P
      > 0.05) and maximum effects were observed when sperm incubated with CLC for
      15min. Longer incubation times, up to 60min, resulted in similar results (P >
      0.05). The amount of cholesterol that incorporated into sperm, increased with
      increasing CLC concentration, in a linear fashion, and each sperm incorporates a
      similar amount of cholesterol (coefficient of variation=12.9+/-0.7%). In
      addition, the cholesterol incorporates into all sperm membranes. Increasing
      membrane cholesterol levels, by adding CLCs to cells, prior to freezing, is a
      simple technology that increases the cryosurvival of bull sperm, and may benefit
      the cryosurvival of many cell types.

PMID- 14969681
TI  - Citrate increases glass transition temperature of vitrified sucrose preparations.
AB  - The aim of this study was to investigate the effect of sodium citrate on the
      properties of dried amorphous sucrose glasses. Addition of sodium citrate to a
      sucrose solution followed by freeze-drying or convective drying resulted in a
      glass transition temperature (Tg) that was higher than the well-studied sucrose
      Tg. This result was obtained either at reduced water content of the analysed
      sample or by removal of water during Modulated DSC analysis. After removal of the
      remaining water ( < 3.5% w/w), a Tg of approximately 105 degrees C was obtained
      at a mass ratio of sodium citrate to sucrose of 0.3. FTIR analysis showed a
      similar increase in Tg as was found with Modulated DSC analysis. The Tg values
      were derived from breaks in the vibrational frequency vs. temperature plots in
      the OH stretching and bending regions. Elevated average strength of hydrogen
      bonding in the sucrose/citrate glass was concluded from the downshift of the OH
      stretching band of 25 cm(-1) and from the reduced wavenumber temperature
      coefficient (WTC). The antisymmetric carboxylate stretch of citrate sensed the
      glass transition of the mixture, from which we conclude that citrate interacts
      with the sucrose OH via its carboxylate groups.

PMID- 14969682
TI  - The application of cryosurgery in the treatment of lung cancer.
AB  - Lung cancer is the commonest cause of cancer death, with a very poor survival
      rate. By the time of diagnosis, most cases are at an advanced stage and about 30%
      present with symptoms caused by central endobronchial obstruction. Endobronchial
      cryosurgery is an effective technique, which can be used to relieve
      tracheobronchial obstruction caused by lung cancer. This report describes the
      technique, using a nitrous oxide cooled cryoprobe, inserted through a
      bronchoscope, to remove the obstruction and reopen the airway. In this study, 476
      consecutive patients (mean age 68.3 years, M:F ratio 1.9:1) with obstructive
      tracheobronchial tumours underwent a mean of 2.4 cryosurgical treatments. Their
      TNM staging was, stage II 6.7%, IIIa 21.0%, IIIb 23.9%, IV 48.4%. Improvement in
      symptom quantification was found with 76.4, 69.0, 59.2, and 42.6% of symptomatic
      patients for haemoptysis, cough, dyspnoea, and chest pain, respectively. Mean
      values for respiratory function improved from 1.38 to 1.41 litres for FEV1 and
      1.91 to 2.04 litres for FVC (p </= 0.0001). Mean performance status improved from
      59.6 to 75.2 for Karnofsky scale and 3.04 to 2.20 for the WHO scale and the
      complication rate was 3.5% of treatments. The Kaplan-Meier median survival was
      8.2 months and 1- and 2-year survival 38.4 and 15.9%, respectively. Survival
      analysis suggested a possible survival advantage over alternative palliative
      techniques. Endobronchial cryosurgery provides a safe and effective method for
      the palliation of otherwise inoperable lung cancer. It has advantages over other
      methods in terms of safety, cost, and a low complication rate. Cryosurgery can be
      repeated as often as required.

PMID- 14969683
TI  - New approach to improving endothelial preservation in cryopreserved arterial
      substitutes.
AB  - The endothelial loss provoked by the methods of vascular cryopreservation used at
      most human vessel banks is one of the main factors leading to the failure of
      grafting procedures performed using cryopreserved vessel substitutes. This study
      evaluates the effects of the storage temperature and thawing protocol on the
      endothelial cell loss suffered by cryopreserved vessels, and optimises the
      thawing temperature and protocol for cryopreserving arterial grafts in terms of
      that producing least endothelial loss. Segments of the common iliac artery of the
      minipig (n = 20) were frozen at a temperature reduction rate of 1 degrees C/min
      in a biological freezer. After storing the arterial fragments for 30 days, study
      groups were established according to the storage temperature (-80, -145 or -196
      degrees C) and subsequent thawing procedure (slow or rapid thawing). Fresh vessel
      segments served as the control group. Once thawed, the specimens were examined by
      light, transmission, and scanning electron microscopy. The covered endothelial
      surface was determined by image analysis. Data for the different groups were
      compared by one way ANOVA. When cryopreservation at each of the storage
      temperatures was followed by slow thawing, the endothelial cells showed improved
      morphological features and viability over those of specimens subjected to rapid
      thawing. Rapidly thawed endothelial cells showed irreversible ultrastructural
      damage such as mitochondrial dilation and rupture, reticular fragmentation, and
      peripheral nuclear condensation. In contrast, slow thawing gave rise to changes
      compatible with reversible damage in a large proportion of the endothelial cells:
      general swelling, reticular dilation, mitochondrial swelling, and nuclear
      chromatin condensation. Gradually thawed cryopreserved arteries showed a lower
      proportion of damaged cells identified by the TUNEL method compared to the
      corresponding rapidly thawed specimens (p < 0.05, for all temperatures). In all
      the groups in which vessels underwent rapid thawing (except at -145 degrees C),
      significant differences (p < 0.05) in endothelial cover values were recorded with
      respect to control groups. Storage of cryopreserved vessels at -80 degrees C
      followed by rapid thawing led to greatest endothelial cell loss (61.36+/-9.06%
      covered endothelial surface), while a temperature of -145 degrees C followed by
      slow thawing was best at preserving the endothelium of the vessel wall (89.38+/
      16.67% surface cover). In conclusion, storage at a temperature of -145 degrees C
      in nitrogen vapour followed by gradual automated thawing seems to be the best way
      of preserving the endothelial surface of the arterial cryograft. This method
      gives rise to best endothelial cell viability and cover values, with obvious
      benefits for subsequent grafting.

PMID- 14969684
TI  - Determination of bull sperm membrane permeability to water and cryoprotectants
      using a concentration-dependent self-quenching fluorophore.
AB  - The objective of this study was to determine the membrane permeability
      characteristics of bovine spermatozoa. These included the hydraulic conductivity
      (Lp), the permeability coefficients (Ps) of four common cryoprotective agents
      (CPAs) and the associated reflection coefficients (sigma). Stopped-flow
      fluorometry was applied in order to capture rapid cell volume changes under
      anisosmotic conditions in the absence or presence of permeant solutes (CPAs).
      This technique utilizes a concentration-dependent self-quenching entrapped
      fluorophore. The resulting cell volume changes were used in three-parameter
      fitting calculations to compute Lp in the absence of permeant solutes and Ps and
      Lp in the presence of permeating solutes (CPAs) at 22 degrees C. The hydraulic
      conductivity in the absence of permeating solutes was estimated to be 0.68+/-0.05
      microm/min/atm (mean+/-SEM). Hydraulic conductivity (Lp) in the presence of CPAs
      was 0.91+/-0.27 (mean+/-SEM), 0.29+/-0.04, 0.42+/-0.05, and 0.39+/-0.03
      microm/min/atm in the presence of dimethylsulfoxide (Me(2)SO), glycerol,
      propylene glycol (PG), and ethylene glycol (EG), respectively. The values for Ps
      were estimated to be 1.72+/-0.36, 1.75+/-0.03, 2.47+/-0.24, and 1.49+/-0.33 x 10(
      3)cm/min for Me(2)SO, glycerol, PG, and EG, respectively. The data were used to
      simulate volume excursions during addition and removal of CPA, to predict the
      different effects of the four CPAs.

PMID- 14969685
TI  - Effect of sugar-phosphate mixtures on the stability of DPPC membranes in
      dehydrated systems.
AB  - The stabilizing role of sugars on dehydrated membranes is well established. The
      formation of a glassy matrix and the direct interaction between the sugars and
      the lipids are some of the mechanisms proposed to be involved in this stabilizing
      effect. Phospholipidic systems have been studied extensively as models for
      biological membranes and also due to the practical applications of liposomes as
      vehicles for drug delivery. In this work, we evaluate the effect of sugar
      phosphate mixtures on the transition temperature of dehydrated 1,2
      dipalmitoylphosphatidylcholine, and also examine some physical characteristics of
      these mixtures, such as the glass transition temperature and water sorption
      properties. The addition of phosphate salts to sugar systems has several
      interesting features that merit its consideration in formulations to protect
      dehydrated labile biomaterials. In particular, sucrose-phosphate mixtures provide
      an interesting alternative to pure saccharide formulations due to their high
      glass transition temperatures and their increased ability to maintain a low
      melting transition temperature in the presence of small amounts of water.

PMID- 14969686
TI  - Cryopreservation of spermatozoa of the terrestrial Puerto Rican frog,
      Eleutherodactylus coqui.
AB  - World-wide reports of amphibian population declines have led to increased
      interest in the reproductive biology of anurans. As a model system, here we
      present evidence for the effective cryoprotection of sperm from the Puerto Rican
      frog, Eleutherodactylus coqui, using mixtures of fetal bovine serum (FBS) and
      dimethylsulfoxide (Me(2)SO), glycerol or sucrose extenders. Using a fluorescent
      dye exclusion assay, we found that 53.9 and 50.4% of all sperm with intact
      membranes prior to freezing maintained membrane integrity after rapid freezing
      and thawing when protected with either a FBS/glycerol or FBS/sucrose solution,
      respectively. The methods reported here may be useful for similar work with many
      of the more than 700 other species in this genus.

PMID- 14969687
TI  - Preserved vascular reactivity of rat renal arteries after cold storage.
AB  - In cultured renal tubular cells hypothermia results in cell damage caused by iron
      dependent formation of reactive oxygen species. It is unknown whether cold
      preservation affects function of renal vessels. Rat renal arcuate arteries were
      stored in a physiological salt solution at 4 degrees C for 24h and compared to
      control arteries (not stored). To some of the stored arteries the iron chelator
      2,2'-dipyridyl was added. Endothelium-independent vasoconstriction was assessed
      by cumulative concentration-response curves for potassium and phenylephrine in a
      small vessel myograph. Endothelium-independent vasodilation was assessed with
      sodium nitroprusside and endothelium-dependent vasodilation with histamine. Cold
      storage for 24h did not affect vascular reactivity of renal small arteries and no
      influence of the iron chelator was seen. Since 24h of cold storage considerable
      damages renal tubular cells both in vitro and after kidney transplantation, these
      results suggest that renal arteries are less sensitive to cold-induced damage
      than tubular cells.

PMID- 14969688
TI  - Tritrichomonas foetus: the role played by iron during parasite interaction with
      epithelial cells.
AB  - The aim of this work was to investigate the role played by iron during
      interaction of Tritrichomonas foetus with cultured epithelial cells. We have
      observed that the growth rate of T. foetus is influenced by the amount of iron
      available into culture medium. When organisms maintained for 24h in iron-depleted
      medium were transferred to an iron-rich one, many protozoan cells exhibited a
      cytokinesis blockage. Parasites maintained in iron-depleted medium exhibited a
      significant increase in cytoadhesion when compared with both controls and
      parasites that had been cultured in medium in which iron was replaced. T. foetus
      collected from iron-depleted medium also exhibited a reduction in its ability to
      destroy epithelial cell monolayers and a reduction in the activity of several
      cysteine proteases. Taken together, the results presented here demonstrate that
      iron may be an extracellular signal, which seems to modulate the ability of T.
      foetus to interact with host epithelial cells.

PMID- 14969689
TI  - Perkinsus marinus, a protozoan parasite of the Eastern oyster (Crassostrea
      virginica): effects of temperature on the uptake and metabolism of fluorescent
      lipid analogs and lipase activities.
AB  - The effects of temperature on the uptake and metabolism of fluorescent labeled
      palmitic acid (FLC16) and phosphatidylcholine (FLPC) and lipase activities in the
      oyster protozoan parasite, Perkinsus marinus, meront stage were tested at 10, 18,
      and 28 degrees C. Temperature significantly affected not only the uptake,
      assimilation, and metabolism of both FLC16 and FLPC in P. marinus, but also its
      triacylglycerol (TAG) lipase activities. The incorporation of both FLC16 and FLPC
      increased with temperature and paralleled the increase in the amount of total
      fatty acids in P. marinus meront cultures. The incorporation of FLC16 was higher
      than FLPC at all temperatures. The percentage of FLC16 metabolized to TAG was
      significantly higher at higher temperatures. Trace amounts of incorporated FLC16
      were detected in monoacylglycerol (MAG) and PC at 18 and 28 degrees C. P. marinus
      meronts metabolized FLPC to TAG, diacylglycerol (DAG), monoacylglycerol (MAG),
      free fatty acids (FFA), phosphatidylethanolamine (PE), and cardiolipin (CL). The
      conversion of FLPC to TAG and PE was highest at 28 degrees C. The relative
      proportions of individual fatty acids and total saturated, monounsaturated and
      polyunsaturated fatty acids changed with temperatures. While total saturated
      fatty acids (SAFAs) increased with temperature, total monounsaturated fatty acids
      (MUFAs) decreased with temperature. Total polyunsaturated fatty acids (PUFAs)
      increased from 28 to 18 degrees C. The findings of increase of total SAFAs and
      decrease of total MUFAs with the increase of temperatures and upward shift of
      total PUFAs from 28 to 18 degrees C suggest that, as in other organisms, P.
      marinus is capable of adapting to changes in environmental temperatures by
      modifying its lipid metabolism. Generally, higher lipase activities were noted at
      higher cultivation temperatures. Both TAG lipase and phospholipase activities
      were detected in P. marinus cells and their extra cellular products (ECP), but
      phospholipase activities in both the cell pellets and ECP were very low. Also,
      lipase activities were much lower in ECP than in the cells. The observations of
      low metabolism, bioconversion of incorporated fluorescent lipid analogs and
      lipase activities at low temperatures are consistent with the low in vitro growth
      rate and low infectivity of P. marinus at low temperatures.

PMID- 14969690
TI  - Impaired clearance of primary but not secondary Brugia infections in IL-5
      deficient mice.
AB  - Eosinophilia in blood and tissues has been strongly associated with helminth
      infections for over a century. In vivo depletion of IL-5, a cytokine crucially
      involved in eosinophilopoiesis with an antibody or through genetic manipulation,
      reproducibly abrogates helminth-induced eosinophilia, but renders mice permissive
      only in some models of parasite infection. In the current study, we compared the
      ability of IL-5(-/-) and B6(+/+) mice to clear intraperitoneal infections with
      Brugia pahangi L3. IL-5(-/-) mice had statistically significantly higher worm
      burdens than B6(+/+). This was true for primary infections, in young as well as
      old mice, suggesting that IL-5 deficient mice are more permissive to Brugian
      infections. This increase in permissiveness seemed to correlate well with the
      drastically reduced eosinophil numbers in the peritoneal cavity, the site of
      infection. In secondary infections, primed IL-5(-/-) mice cleared infections in
      an accelerated manner, comparable with B6(+/+) mice. These observations suggest
      that IL-5 induced eosinophilia is more important in the control of a primary
      infection in naive mice than a secondary infection in primed mice.

PMID- 14969691
TI  - Trypanosoma brucei: functions of RBP16 cold shock and RGG domains in
      macromolecular interactions.
AB  - The RNA binding protein RBP16 regulates mitochondrial RNA editing and stability
      in Trypanosoma brucei. To aid in understanding the biochemical mechanisms of
      RBP16 function, we analyzed the RNA and protein binding capacity of RBP16 and its
      individual cold shock (CSD) and RGG domains. Both recombinantly expressed domains
      possess RNA binding activity. However, the specificity and affinity of RBP16 for
      gRNA is mediated predominantly through the interaction of the CSD with poly(U).
      The RGG domain contributes to the association between full length RBP16 and gRNA,
      as it was required for maximal binding. We further demonstrate that both domains
      contribute to maximal binding of RBP16 to the mitochondrial p22 protein. However,
      p22 can interact with the CSD alone and stimulate its gRNA binding activity.
      Thus, the CSD is primary in RBP16 interactions, while the RGG domain enhances the
      capacity of the CSD to bind both RNA and protein. These results suggest a model
      for RBP16 molecular interactions.

PMID- 14969692
TI  - Trypanosoma cruzi: molecular cloning and characterization of the S
      adenosylhomocysteine hydrolase.
AB  - S-Adenosylhomocysteine (AdoHcy) hydrolase has emerged as an attractive target for
      antiparasitic drug design because of its role in the regulation of all S
      adenosylmethionine-dependent transmethylation reactions, including those
      reactions crucial for parasite replication. From a genomic DNA library of
      Trypanosoma cruzi, we have isolated a gene that encodes a polypeptide containing
      a highly conserved AdoHcy hydrolase consensus sequence. The recombinant T. cruzi
      enzyme was overexpressed in Escherichia coli and purified as a homotetramer. At
      pH 7.2 and 37 degrees C, the purified enzyme hydrolyzes AdoHcy to adenosine and
      homocysteine with a first-order rate constant of 1 s(-1) and synthesizes AdoHcy
      from adenosine and homocysteine with a pseudo-first-order rate constant of 3 s(
      1) in the presence of 1 mM homocysteine. The reversible catalysis depends on the
      binding of NAD(+) to the enzyme. In spite of the significant structural homology
      between the parasitic and human AdoHcy hydrolase, the K(d) of 1.3 microM for
      NAD(+) binding to the T. cruzi enzyme is approximately 11-fold higher than the
      K(d) (0.12 microM) for NAD(+) binding to the human enzyme.

PMID- 14969693
TI  - Plasmodium chabaudi adami: interferon-gamma but not IL-2 is essential for the
      expression of cell-mediated immunity against blood-stage parasites in mice.
AB  - Cell-mediated immunity (CMI) may be important in immunity against blood-stage
      malaria. Accordingly, we examined the role of type 1 cytokines in the resolution
      of Plasmodium chabaudi adami malaria in mice genetically modified to have type 1
      cytokine gene defects. Parasitemia was prolonged in double knockout (IL-2(-/-),
      IFNgamma(-/-)) mice compared to control mice. Despite deficiencies in gammadelta
      T cell and B cell subsets, these mice produced anti-malarial antibodies and
      eventually cured their infections, possibly by antibody-mediated immunity.
      However, because acute P. c. adami parasitemia may also be suppressed by CMI, the
      requirements for IL-2 and IFNgamma were evaluated in mice lacking B cells and
      functional IL-2 or IFNgamma genes. Acute malaria in J(H)(-/-), IL-2(-/-) mice was
      prolonged, but eventually cured. In contrast, J(H)(-/-), IFNgamma(-/-) mice
      developed unremitting parasitemia. These data strongly suggest that IFNgamma, but
      not IL-2, plays an essential role in the expression of CMI against P. c. adami
      infections. This finding may prove useful in developing malarial vaccines aimed
      at inducing CMI.

PMID- 14969694
TI  - Characterization of an ecto-5'-nucleotidase (EC 3.1.3.5) activity in intact cells
      of Trichomonas vaginalis.
AB  - The enzymatic properties of an ecto-5'-nucleotidase were described in Trichomonas
      vaginalis. The enzyme hydrolyzes nucleoside monophosphates in optimum pH values
      of 7.5 and 6.5 for the 30236 strain and for the 30238 strain, respectively.
      Mg(2+) and Ca(2+) were activators of AMP hydrolysis in both strains. The apparent
      K(m) (Michaelis constant) values for Mg(2+)-AMP were 111.4+/-28.1 microM (mean+/
      SD, n=3) for 30236 strain and 420.2+/-35.7 microM (mean+/-SD, n=3) for 30238
      strain. The ecto-5'-nucleotidase activity was insensitive to levamisole and
      tetramisole, inhibitors of alkaline phosphatases, whereas alpha,beta-methylene
      ADP inhibited the enzymatic activity of both strains. Our results showed that the
      AMP hydrolysis presents differences in some kinetic parameters between the two
      strains investigated. An analysis of the enzymatic chain involved in the ATP
      hydrolysis to adenosine will contribute to understanding the biochemical aspects
      of the parasite and the mechanisms related to host-parasite interactions.

PMID- 14969695
TI  - Schistosoma mansoni miracidia transformed by particle bombardment infect
      Biomphalaria glabrata snails and develop into transgenic sporocysts.
AB  - Miracidia (and adults) of Schistosoma mansoni which had been subjected to
      particle bombardment with a plasmid DNA encoding enhanced green fluorescent
      protein (EGFP) under control of the S. mansoni heat shock protein 70 (HSP70)
      promoter and termination elements were shown to express the reporter gene.
      Bombarded miracidia were able to penetrate and establish in Biomphalaria glabrata
      the intermediate host snail. Gold particles could be detected in the germ balls
      of parasites in paraffin-sections of snail tissue. The bombarded miracidia were
      able to develop normally and to transform into mother sporocysts. Reporter gene
      activity could be determined at 10 days post-infection by RT-PCR in snail
      tissues, but not by microscopy or Western blot which probably reflected sub
      optimal expression levels of constructs. Our findings indicated that it is
      feasible to return transgenic miracidia to the life cycle, a crucial step for the
      establishment of a transgenesis system for schistosomes.

PMID- 14969703
TI  - Models of phage growth and their applicability to phage therapy.
AB  - Phage therapy is complicated by the self-replicating nature of phage. It is
      difficult to extrapolate from in vitro phage growth data to in vivo expectations,
      difficult to interpret in vivo data and difficult to generalize from one in vivo
      situation to another. Various generic models of phage growth have been used as
      the theoretical basis for understanding the kinetics of phage therapy. Here, we
      have experimentally tested the efficacy of such simple models to predict,
      qualitatively and quantitatively, the growth of phage and the phage proliferation
      threshold in vitro. Naturally occurring, antibiotic-resistant bacteria were used
      to measure the growth of phage in vivo. In homogenous, in vitro environments, the
      models were predictive of T4 phage growth on Escherichia coli RR1. However, the
      models were not able to predict growth of T4 phage or K1-5 phage in the more
      complex environment of the rat's digestive tract. To explore fully the kinetics
      of phage therapy, more complex models need to be devised. We suggest that it may
      be necessary to consider and model the interactions between phage growth
      parameters and bacterial growth parameters.

PMID- 14969704
TI  - Periodic local disturbance in host-parasitoid metapopulations: host suppression
      and parasitoid persistence.
AB  - Within many agricultural systems, insect pests and their natural enemies are
      forced to persist as a metapopulation, continuously recolonizing patches
      following disturbance through harvesting or spraying with insecticides. Despite
      the need to understand factors influencing biocontrol success, few theoretical
      studies of host-parasitoid interactions have examined the potential impact of
      local disturbance within a metapopulation framework. Here, we add periodic local
      mortality to series of classical host-parasitoid models to examine its effect on
      host suppression and parasitoid persistence. Using a deterministic lattice model,
      we show that despite the wide range of complex dynamics generated at the patch
      level, the region wide pattern of disturbance is the key factor influencing host
      suppression. The level of host suppression achieved can be understood in terms of
      both the strength of density dependent parasitism, and the relative amounts of
      host and parasitoid mixing amongst patches of different ages. Local dispersal
      among patches is sufficient to ensure coexistence of the host and parasitoid,
      though persistence is not necessarily associated with the formation of self
      organized spatial structures reported in previous studies. Finally, a stochastic
      version of the model is developed, in order to highlight how the effects of
      demographic stochasticity may influence biocontrol success in highly disturbed
      agricultural systems.

PMID- 14969705
TI  - Positional entropy during pigeon homing II: navigational interpretation of
      Bayesian latent state models.
AB  - In these two companion papers we introduce a new approach to the analysis of bird
      navigation which brings together several novel mathematical and technical
      applications. Miniaturized GPS logging devices provide track data of sufficiently
      high spatial and temporal resolution that considerable variation in flight
      behaviour can be observed remotely from the form of the track alone. We analyse a
      fundamental measure of bird flight track complexity, spatio-temporal entropy, and
      explore its state-like structure using a probabilistic hidden Markov model. The
      emergence of a robust three-state structure proves that the technique has
      analytical power, since this structure was not obvious in the tracks alone. We
      propose the hypothesis that positional entropy is indicative of underlying
      navigational uncertainty, and that familiar area navigation may break down into
      three states of navigational confidence. By interpreting the relationship between
      these putative states and features on the map, we are able to propose a number of
      hypothetical navigational strategies feeding into these states. The first of
      these two papers details the novel technical developments associated with this
      work and the second paper contains a navigational interpretation of the results
      particularly with respect to visual features of the landscape.

PMID- 14969706
TI  - Positional entropy during pigeon homing I: application of Bayesian latent state
      modelling.
AB  - In these two companion papers, we introduce a new approach to the analysis of
      bird navigation which brings together several novel mathematical and technical
      applications. Miniaturized GPS logging devices provide track data of sufficiently
      high spatial and temporal resolution that considerable variation in flight
      behaviour can be observed remotely from the form of the track alone. We analyse a
      fundamental measure of bird flight track complexity, spatio-temporal entropy, and
      explore its state-like structure using a probabilistic hidden Markov model. The
      emergence of a robust three-state structure proves that the technique has
      analytical power, since this structure was not obvious in the tracks alone. We
      propose the hypothesis that positional entropy is indicative of underlying
      navigational uncertainty, and that familiar area navigation may break down into
      three states of navigational confidence. By interpreting the relationship between
      these putative states and features on the map, we are able to propose a number of
      hypothetical navigational strategies feeding into these states. The first of
      these two papers details the novel technical developments associated with this
      work and the second paper contains a navigational interpretation of the results
      particularly with respect to visual features of the landscape.

PMID- 14969707
TI  - An information-processing analysis of the functional architecture of the primate
      neocortex.
AB  - Working at the systems level of analysis, we will use the term functional
      architecture to concern what processing components exist, how they are
      interconnected, and what information-processing functions each is involved in. In
      this paper, experimental evidence for the primate neocortex is analysed for
      conclusions concerning the existence of neural areas, for corticocortical
      connectivity among neural areas, and for the involvement of each cortical neural
      area in the functioning of the brain. We characterize the information-processing
      function for each neural area in terms of the types of information it is
      associated with, and conceive of its activity as processing, storage and
      transmission of data of the corresponding types for that area. We also adapt
      concepts of goal, plan, sequence, event and context for the description of
      information processing in the neocortex. This analysis shows that the primate
      neocortex consists in the main of a perception hierarchy, an action hierarchy and
      connections between them. In other words, from an information-processing point of
      view, the primate neocortex has a hierarchical perception-action architecture.

PMID- 14969708
TI  - A computational model for the primate neocortex based on its functional
      architecture.
AB  - Experimental evidence has shown that the primate neocortex consists in the main
      of a set of cortical regions which form a perception hierarchy, an action
      hierarchy and connections between them. By using a computer science analysis, we
      develop a computational architecture for the brain in which each cortical region
      is represented by a computational module with processing and storage abilities.
      Modules are interconnected according to the connectivity of the corresponding
      cortical regions. We develop computational principles for designing such a
      hierarchical and parallel computing system. We demonstrate this approach by
      proposing a causal functioning model of the brain. We report on results obtained
      with an implementation of this model. We conclude with a brief discussion of some
      consequences and predictions of our work.

PMID- 14969709
TI  - Critical conditions for pattern formation and in vitro tubulogenesis driven by
      cellular traction fields.
AB  - In vitro angiogenesis assays have shown that tubulogenesis of endothelial cells
      within biogels, like collagen or fibrin gels, only appears for a critical range
      of experimental parameter values. These experiments have enabled us to develop
      and validate a theoretical model in which mechanical interactions of endothelial
      cells with extracellular matrix influence both active cell migration--haptotaxis-
      and cellular traction forces. Depending on the number of cells, cell motility and
      biogel rheological properties, various 2D endothelial patterns can be generated,
      from non-connected stripe patterns to fully connected networks, which mimic the
      spatial organization of capillary structures. The model quantitatively and
      qualitatively reproduces the range of critical values of cell densities and
      fibrin concentrations for which these cell networks are experimentally observed.
      We illustrate how cell motility is associated to the self-enhancement of the
      local traction fields exerted within the biogel in order to produce a pre
      patterning of this matrix and subsequent formation of tubular structures, above
      critical thresholds corresponding to bifurcation points of the mathematical
      model. The dynamics of this morphogenetic process is discussed in the light of
      videomicroscopy time lapse sequences of endothelial cells (EAhy926 line) in
      fibrin gels. Our modeling approach also explains how the progressive appearance
      and morphology of the cellular networks are modified by gradients of
      extracellular matrix thickness.

PMID- 14969710
TI  - Maximization principles and daisyworld.
AB  - We investigate whether the equilibrium time-averaged state of a self-organizing
      system with many internal degrees of freedom, 2D-daisyworld, can be described by
      optimizing a single quantity. Unlike physical systems where a principle of
      maximum energy production has been observed, daisyworld follows evolutionary
      dynamics rather than Hamiltonian dynamics. We find that this is sufficient to
      invalidate the maximum entropy production principle, finding instead a different
      principle, that the system self-organizes to a state which maximizes the amount
      of life.

PMID- 14969711
TI  - Structural cost of shoot modules and its implications on plant potential fitness
      in a Mediterranean perennial shrub, Retama sphaerocarpa (L.) Boiss.
AB  - This paper introduces a methodology to analyse the structural costs on plant
      potential fitness, empirically exemplified in the hierarchical shoot system of a
      Mediterranean perennial plant, Retama sphaerocarpa (L.) Boiss. During growing
      season every year (March-August), the terminal shoot (which is the basic unit of
      growth) develops inflorescences, flowers and fruits, as well as new shoots (first
      , second- and third-order branching shoots) which have the potential to "behave"
      as terminal shoots in the following year. Different morphological and
      demographical aspects of the modules within the terminal shoot were measured in
      100 terminal shoots selected from different plants of a natural population of R.
      sphaerocarpa. Complementary samples of 100 shoots of different branching orders
      were collected to obtain biomass estimations of the terminal shoots. We propose a
      simple procedure to estimate structural cost (biomass investment) on plant
      potential fitness (flowering buds) as a methodology for interpreting and
      comparing the consequences on fitness of different plant growth patterns. The
      results of this study exemplify how differential allocation patterns among plant
      structural modules, depending on their position within the shoot system, can be
      quantified to estimate their influence upon plant potential fitness.

PMID- 14969712
TI  - An allometric model for trees.
AB  - This paper presents a general mathematical model for the morphometric description
      of trees. This model is based on the introduction of fractal theory, and more
      particularly of the concept of self-similarity, into a statistical physics
      rationale. Fractal theory provides the necessary tools to describe the complexity
      of tree structure. Statistics, when applied to physics, makes it possible to
      explain the properties of complex objects starting from their components. The
      combination of both tools allowed us to develop a theoretical model that is the
      probability density function of the morphometric lengths of trees. An example of
      validation of this law is given here: the theoretical model of morphometric
      lengths is compared with experimental data of Cupressocyparis.

PMID- 14969713
TI  - Genetic network models and statistical properties of gene expression data in
      knock-out experiments.
AB  - It is shown here how gene knock-out experiments can be simulated in Random
      Boolean Networks (RBN), which are well-known simplified models of genetic
      networks. The results of the simulations are presented and compared with those of
      actual experiments in S. cerevisiae. RBN with two incoming links per node have
      been considered, and the Boolean functions have been chosen at random among the
      set of so-called canalizing functions. Genes are knocked-out (i.e. silenced) one
      at a time, and the variations in the expression levels of the other genes, with
      respect to the unperturbed case, are considered. Two important variables are
      defined: (i) avalanches, which measure the size of the perturbation generated by
      knocking out a single gene, and (ii) susceptibilities, which measure how often
      the expression of a given gene is modified in these experiments. A remarkable
      observation is that the distributions of avalanches and susceptibilities are very
      robust, i.e. they are very similar in different random networks; this should be
      contrasted with the distribution of other variables that show a high variance in
      RBN. Moreover, the distribution of avalanches and susceptibilities of the RBN
      models are close to those observed in actual experiments performed with S.
      cerevisiae, where the changes in gene expression levels have been recorded with
      DNA microarrays. These findings suggest that these distributions might be
      "generic" properties, common to a wide range of genetic models and real genetic
      networks. The importance of such generic properties is discussed.

PMID- 14969714
TI  - The effect of elevated extracellular glucose on adherens junction proteins in
      cultured rat heart endothelial cells.
AB  - Vascular permeability is a proof of vascular endothelial cell dysfunction induced
      by diabetes. Vascular permeability is directly related to the width of
      intercellular endothelial cells junctions, which may become permeable to
      macromolecules as a result of a change in endothelial cell shape. To determine
      the role of hyperglycemia in endothelial cell shape, the study examined the
      effect of high concentrations of glucose on the shape of cultured rat heart
      endothelial cells. This result indicated that the high-glucose-induced changes in
      the morphology of endothelial cells, via the glucose-mediated reorganization of F
      actin. In endothelial cells, the actin cytoskeleton is tethered to the zonula
      adherens and focal adhesions, which mediate cell-cell and cell-matrix
      interactions respectively. The present study demonstrated that the high-glucose
      induced changes in the actin-binding protein such as filamin, zonula adherens
      proteins such as alpha-, beta-, and gamma-catenin, focal adhesions proteins such
      as focal adhesion kinase, paxillin, and tyrosine phosphorylation of paxillin. It
      appears that differences in expression of adherens junctions molecules on rat
      heart endothelial cells in response to high glucose reflect endothelial glucose
      toxicity, which may also induce endothelial dysfunction in diabetes.

PMID- 14969715
TI  - Up-regulation of mitochondrial transcription factor 1 mRNA levels by GH in VSMC.
AB  - It is well known that growth hormone (GH) is involved in the development of
      arteriosclerosis in which vascular smooth muscle cells (VSMC) play an important
      role. In this study, we attempted to specify the genes up- or down-regulated by
      recombinant human GH (rhGH) in VSMC using a differential display method. We found
      that rhGH increased cytochrome oxidase subunit II/III mRNA in VSMC. Furthermore,
      the mRNA for mitochondrial transcription factor 1 (mtTF1), which stimulates the
      expression of cytochrome oxidase subunit II/III, was found to be up-regulated by
      rhGH in a dose dependent manner using a quantitative PCR method. On the other
      hand, IGF-I alone did not change mtTF1 mRNA levels. In rat L6 myoblasts and rat
      H4-II-E hepatocytes, rhGH did not change mtTF1 mRNA levels. Pretreatment with a
      JAK2 inhibitor AG490 (10 nM) and a MEK inhibitor PD98059 (10 microM) suppressed
      rhGH-induced rise in mtTF1 mRNA levels of VSMC to the control levels.
      Pretreatment with a PI-3kinase inhibitor wortomannin (1 nM) did not suppress rhGH
      induced rise in mtTF1 mRNA levels. These findings suggest that GH up-regulates
      mtTF1 mRNA levels through JAK2 and MEK signaling in VSMC.

PMID- 14969716
TI  - Endogenous ouabain-like factor (OLF) secretion is modulated by nicotinic
      mechanisms in rat adrenocortical cells.
AB  - This study tested the hypothesis that rat adrenocortical secretion of endogenous
      ouabain-like factor (OLF) is regulated by nicotinic mechanisms. OLF secreted by
      dispersed cell suspensions of zona glomerulosa (ZG) and fasciculata/reticularis
      (ZFR) cells was found to co-elute with authentic ouabain by reverse phase HPLC;
      OLF concentrations in cell supernatants were measured by radioimmunoassay.
      Nicotine (10(-6) - 10(-3) M) stimulated significant OLF secretion in rat
      adrenocortical cells. Acetylcholine (10(-7) - 10(-4) M) and eserine (10(-7) - 10(
      3) M) stimulated OLF secretion in ZG cells at lower concentrations and stimulated
      at higher concentrations. Acetylcholine had no effect on ZFR secretion of OLF,
      but eserine stimulated OLF secretion. ACTH (10(-8) M) strongly potentiated the
      OLF stimulatory effect of nicotine in ZG cells; however significant interactions
      between nicotine and ACTH or angiotensin II on OLF secretion in ZFR cells were
      not apparent. The ganglionic blockers hexamethonium and mecamylamine further
      potentiated the effect of nicotine, implicating nicotinic acetylcholine receptors
      (nAChRs) in regulation of OLF secretion. The alpha7-receptor antagonist
      methyllycaconitine (MLA) dose-dependently inhibited the effect of nicotine in the
      ZG cells, and in ZFR cells MLA potentiated nicotine-induced OLF secretion. These
      data suggest that nicotinic regulation may underlie OLF secretion by rat
      adrenocortical cells, and strongly suggest presence of functional nicotinic
      acetylcholine receptors on these cells.

PMID- 14969717
TI  - Anti-lipid deposition effect of HMG-CoA reductase inhibitor, pitavastatin, in a
      rat model of hypertension and hypercholesterolemia.
AB  - Since the rat is an atherosclerosis-resistant species, the study of
      atherosclerosis using rats is limited. The present study was undertaken to
      develop an atherosclerotic model in rats, to investigate the effect of nitric
      oxide (NO) inactivation and hyperlipidemia, and to evaluate the effect of
      pitavastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA
      reductase) inhibitor, on NO inactivation and on hyperlipidemia-induced changes in
      the cardiovascular system. Four-month-old male spontaneously hypertensive
      hyperlipidemic rats (SHHR) and Sprague-Dawley (SD) rats were used to study 1) the
      effect of the period of treatment with N(G)-nitro-L-arginine methyl ester (L
      NAME, 100 mg/L) on high fat diet (HFD)-treated SHHR and SD rats, and 2) the
      effect of pitavastatin (Pit, 0.3 mg/kg/day) on the changes in the aorta of L-NAME
      and HFD-treated SHHR and SD rats. L-NAME administration for 1 month then HFD
      feeding for 2 months markedly increased the deposition of lipids and the
      thickness of the endothelium in SHHR. Continuous L-NAME treatment with HFD
      produced severe injury and stripped of endothelium in both strains. The plasma
      total cholesterol of L-NAME + HFD-treated and L-NAME + HFD + Pit-treated SHHR was
      significantly higher than that of control SHHR. Lipid deposition, however, was
      comparatively less in the aorta of L-NAME + HFD + Pit-treated SHHR. The
      concentration of cholesterol in the aorta of control SHHR was significantly lower
      than that in the aorta of L-NAME + HFD-treated SHHR, whereas that of L-NAME + HFD
      + Pit-treated SHHR was the same as that in control SHHR. These data indicated
      that Pit blocked lipid deposition in the aorta of L-NAME + HFD treated SHHR
      without changing plasma lipid profiles. In conclusion, NO inactivation and HFD
      induce lipid deposition in the endothelium, and the HMG-CoA reductase inhibitor
      blocks the deposition in SHHR.

PMID- 14969718
TI  - Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally
      active opioid analgesic from the Thai medicinal herb Mitragyna speciosa.
AB  - Mitragynine is an indole alkaloid isolated from the Thai medicinal plant
      Mitragyna speciosa. We previously reported the morphine-like action of
      mitragynine and its related compounds in the in vitro assays. In the present
      study, we investigated the opioid effects of 7-hydroxymitragynine, which is
      isolated as its novel constituent, on contraction of isolated ileum, binding of
      the specific ligands to opioid receptors and nociceptive stimuli in mice. In
      guinea-pig ileum, 7-hydroxymitragynine inhibited electrically induced contraction
      through the opioid receptors. Receptor-binding assays revealed that 7
      hydroxymitragynine has a higher affinity for micro-opioid receptors relative to
      the other opioid receptors. Administration of 7-hydroxymitragynine (2.5-10 mg/kg,
      s.c.) induced dose-dependent antinociceptive effects in tail-flick and hot-plate
      tests in mice. Its effect was more potent than that of morphine in both tests.
      When orally administered, 7-hydroxymitragynine (5-10 mg/kg) showed potent
      antinociceptive activities in tail-flick and hot-plate tests. In contrast, only
      weak antinociception was observed in the case of oral administration of morphine
      at a dose of 20 mg/kg. It was found that 7-hydroxymitragynine is a novel opioid
      agonist that is structurally different from the other opioid agonists, and has
      potent analgesic activity when orally administered.

PMID- 14969719
TI  - Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal
      plants associated with anticancer.
AB  - Cancer prevention and treatment using traditional Chinese medicines have
      attracted increasing interest. This study characterizes antioxidant activity and
      phenolic compounds of traditional Chinese medicinal plants associated with
      anticancer, comprising 112 species from 50 plant families. The improved ABTS(*+)
      method was used to systematically assess the total antioxidant capacity (Trolox
      equivalent antioxidant capacity, TEAC) of the medicinal extracts. The TEAC values
      and total phenolic content for methanolic extracts of herbs ranged from 46.7 to
      17,323 micromol Trolox equivalent/100 g dry weight (DW), and from 0.22 to 50.3 g
      of gallic acid equivalent/100 g DW, respectively. A positive, significant linear
      relationship between antioxidant activity and total phenolic content (all R(2)
      values>/=0.95) showed that phenolic compounds were the dominant antioxidant
      components in the tested medicinal herbs. Major types of phenolic compounds from
      most of the tested herbs were preliminarily identified and analyzed, and mainly
      included phenolic acids, flavonoids, tannins, coumarins, lignans, quinones,
      stilbenes, and curcuminoids. These medicinal herbs exhibited far stronger
      antioxidant activity and contained significantly higher levels of phenolics than
      common vegetables and fruits. Traditional Chinese medicinal plants associated
      with anticancer might be potential sources of potent natural antioxidants and
      beneficial chemopreventive agents.

PMID- 14969720
TI  - Photodynamic effect of novel chlorin e6 derivatives on a single nerve cell.
AB  - Chlorin e(6) and its derivatives are promising sensitizers for photodynamic
      therapy (PDT). In order to compare the photodynamic effects of 8 novel
      derivatives of chlorin e(6) and to explore some mechanisms of their effects at
      the cellular level, we studied PDT-induced changes in bioelectric activity of
      crayfish mechanoreceptor neuron that was used as a sensitive experimental model.
      Neurons were insensitive to red laser irradiation (632.8 nm; 0.3 W/cm(2)) or to
      photosensitizers alone, but changed firing rate and died under the photodynamic
      effect of nanomolar concentrations of sensitizers. The dynamics of neuron
      responses depended on photosensitizer type and concentration. The dependence of
      neuron lifetime on photosensitizer concentration allowed comparing efficiencies
      of different photosensitizers. Radachlorin was the most potent photosensitizer
      comparable with mTHPC. High photodynamic efficiency of some chlorin e(6)
      derivatives was related to weak dependence of neuron lifetime on sensitizer
      concentration, indicating to the initiation of 2-3 secondary processes such as
      free radical membrane damage by one absorbed photon. Photodynamic efficiency of
      sensitizers depended on amphiphilicity influencing their intracellular
      localization.

PMID- 14969721
TI  - The alteration of intracellular signaling on the smooth muscle cells contraction
      in cat esophagitis.
AB  - We investigated the alteration of signal transduction after acute esophagitis in
      cat lower esophageal sphincter (LES). Acute esophagitis (AE) was induced by
      perfusion with 0.1N HCl at a rate of 1 ml/min for 45 min over three consecutive
      days. Acetylcholine (ACh)-induced contraction was inhibited by M3>> M1 or M2
      antagonists in normal LES. In AE, inhibition by M2 antagonists increased
      significantly, so that contraction was inhibited by M3> M2> M1 antagonists and
      the expression of M2 and M3 receptors were increased when compared to normal LES.
      In normal cells, ACh-induced contractions were antagonized by antibody against
      G(q/11) and the phosphatidylinositol-specific phospholipase C (PI-PLC)
      antagonist, U73122. The phosphatidylcholine-specific phospholipase C (PC-PLC)
      inhibitor, D609, or the phospholipase D inhibitor, propranolol had no effects on
      contraction in normal LES. However, in AE, G(q/11), and G(i3) antibodies reduced
      ACh-induced contraction and U73122, propranolol and D609 also reduced the
      contraction. In AE, we found that the expressions of G protein subtypes were
      increased but the expression of PLCbeta1, and PLCgamma1 were decreased when
      compared to normal LES. In conclusion, experimental esophagitis may alter the
      signal transduction by ACh in LES. ACh-induced contraction is mediated by M3
      receptor, G(q/11) and PI-PLC in normal LES. However, in AE, the contractions are
      mediated by M2, M3 receptor, G(q/11) and G(i3). PC-PLC and PLD as PI-PLC are also
      involved in ACh-induced cell contraction in AE.

PMID- 14969722
TI  - Structure and function of RNA polymerase II.

PMID- 14969723
TI  - The mediator complex.

PMID- 14969724
TI  - Structure and function of the TFIID complex.

PMID- 14969725
TI  - Tetratricopeptide repeats of Tfc4 and a limiting step in the assembly of the
      initiation factor TFIIIB.

PMID- 14969726
TI  - Mechanism of RNA polymerase I transcription.

PMID- 14969727
TI  - Functional properties of ATP-dependent chromatin remodeling enzymes.

PMID- 14969728
TI  - Histone acetyltransferase proteins contribute to transcriptional processes at
      multiple levels.

PMID- 14969729
TI  - Posttranslational modifications of histones by methylation.

PMID- 14969731
TI  - Profiling of genes associated with transcriptional responses in mouse hippocampus
      after transient forebrain ischemia using high-density oligonucleotide DNA array.
AB  - Several cascades of changes in gene expression have been shown to be involved in
      the neuronal injury after transient cerebral ischemia; however, little is known
      about the profile of genes showing alteration of expression in a mouse model of
      transient forebrain ischemia. We analyzed the gene expression profile in the
      mouse hippocampus during 24 h of reperfusion, after 20 min of transient forebrain
      ischemia, using a high-density oligonucleotide DNA array. Using statistical
      filtration (Welch's ANOVA and Welch's t-test), we identified 25 genes with a more
      than 3.0-fold higher or lower level of expression on average, with statistical
      significance set at p<0.05, in at least one ischemia-reperfusion group than in
      the sham group. Using unsupervised clustering methods (hierarchical clustering
      and k-means clustering algorithms), we identified four types of gene expression
      pattern that may be associated with the response of cell populations in the
      hippocampus to an ischemic insult in this mouse model. Functional classification
      of the 25 genes demonstrated alterations of expression of several kinds of
      biological pathways, regulating transcription (Bhlhb2, Jun, c-fos, Egr1, Egr2,
      Fosb, Junb, Ifrd1, Neurod6), the cell cycle (c-fos, Fosb, Jun, Junb, Dusp1),
      stress response (Dusp1, Dnajb1, Dnaja4), chaperone activity (Dnajb1, Dnaja4) and
      cell death (Ptgs2, Gadd45g, Tdag51), in the mouse hippocampus by 24 h of
      reperfusion. Using hierarchical clustering analysis, we also found that the same
      25 genes clearly discriminated between the sham group and the ischemia
      reperfusion groups. The alteration of expression of 25 genes identified in this
      study suggests the involvement of these genes in the transcriptional response of
      cell populations in the mouse hippocampus after transient forebrain ischemia.

PMID- 14969732
TI  - GABA(B) receptor-mediated regulation of P2X7 receptor expression in the gerbil
      hippocampus.
AB  - In the present study, the P(2)X(7) receptor expression in the gerbil hippocampus
      and GABA-mediated responses of its expression was investigated in order to
      identify the roles of the P(2)X(7) receptor on seizure activity and recovery
      mechanisms. P(2)X(7) receptor immunoreactivity in seizure-resistant (SR) gerbils
      was similar to that in pre-seizure group of seizure-sensitive (SS) gerbils. The
      administration of baclofen, a GABA(B) receptor agonist, P(2)X(7) receptor
      immunoreactivity was decreased in the mossy fiber, compared with that of non
      treated gerbils, whereas treatment with phaclofen, a GABA(B) receptor antagonist,
      elevated P(2)X(7) receptor expression. Neither the treatments with GABA(A)
      receptor agonist nor antagonist affected P(2)X(7) receptor expression in the
      hippocampus. These findings suggest that altered P(2)X(7) receptor expression may
      not be involved in the epileptogenesis or seizure activity in gerbils, and
      presynaptic GABA(B) receptor-mediated actions may be closely related with the
      regulation of P(2)X(7) receptor expression in the gerbil hippocampus.

PMID- 14969733
TI  - Changes in methylation pattern of NMDA receptor NR2B gene in cortical neurons
      after chronic ethanol treatment in mice.
AB  - Chronic ethanol treatment produced an increase in the rate of NR2B gene
      expression in adult cortex and cultured fetal cortical neurons. To determine the
      possible molecular mechanism involved in the upregulation of NR2B gene
      expression, we studied methylation in CpG island in mouse fetal cortical neurons.
      Our results demonstrate that chronic ethanol administration causes demethylation
      of cytosine residues in CpG island in cortical neurons which may be responsible
      for the changes in the expression of NR2B gene.

PMID- 14969734
TI  - Mice with reduced brain-derived neurotrophic factor expression show decreased
      choline acetyltransferase activity, but regular brain monoamine levels and
      unaltered emotional behavior.
AB  - The "neurotrophin hypothesis" of depression predicts that depressive disorders in
      humans coincide with a decreased activity and/or expression of brain-derived
      neurotrophic factor (BDNF) in the brain. Therefore, we investigated whether mice
      with a reduced BDNF expression due to heterozygous gene disruption demonstrate
      depression-like neurochemical changes or behavioral symptoms. BNDF protein levels
      of adult BDNF(+/-) mice were reduced to about 60% in several brain areas
      investigated, including the hippocampus, frontal cortex, striatum, and
      hypothalamus. The content of monoamines (serotonin, norepinephrine, and dopamine)
      as well as of serotonin and dopamine degradation products was unchanged in these
      brain regions. By contrast, choline acetyltransferase activity was significantly
      reduced by 19% in the hippocampus of BDNF(+/-) mice, indicating that the
      cholinergic system of the basal forebrain is critically dependent on sufficient
      endogenous BDNF levels in adulthood. Moreover, BDNF(+/-) mice exhibited normal
      corticosterone and adrenocorticotropic hormone (ACTH) serum levels under baseline
      conditions and following immobilization stress. In a panel of behavioral tests
      investigating locomotor activity, exploration, anxiety, fear-associated learning,
      and behavioral despair, BDNF(+/-) mice were indistinguishable from wild-type
      littermates. Thus, a chronic reduction of BDNF protein content in adult mice is
      not sufficient to induce neurochemical or behavioral alterations that are
      reminiscent of depressive symptoms in humans.

PMID- 14969735
TI  - Increased expression of AMPA receptor subunits in the nucleus of the solitary
      tract in the spontaneously hypertensive rat.
AB  - The expression of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
      receptor subunits GluR1-4 in the nucleus of the solitary tract (NTS) of adult
      Wistar rats was examined by polymerase chain reaction (PCR), and the neuronal
      localisation of these receptor subunits in the NTS were confirmed by
      immunohistochemistry using subunit-specific antibodies. Semi-quantitative PCR was
      used to investigate differences in AMPA receptor subunit expression between
      spontaneously hypertensive rats (SH) and age-matched normotensive Wistar Kyoto
      rats (WKY). All four receptor subunits were expressed in both strains, but
      compared to WKY, total AMPA receptor and the GluR3 mRNA expressions were
      significantly higher in SH. No differences were detected in cDNA form the
      cerebral cortex or cerebellum. Immunolabelling for GluRs 1, 2 and 2/3 in the
      neuropil relative to neuronal somata in the cardioregulatory areas of the NTS
      appeared to be increased in SH, with an overall increase in the density of
      GluR2/3 labelling in the medial and commissural NTS of SH. These results indicate
      a possible role for changes in AMPA receptor subunit expression in NTS neurones,
      involving an increase in GluR3 associated with development of hypertension in SH.

PMID- 14969736
TI  - Neuroprotection by cyclosporin A following transient brain ischemia correlates
      with the inhibition of the early efflux of cytochrome C to cytoplasm.
AB  - The efflux of mitochondrial protein cytochrome C to cytoplasm is one of the key
      events of mitochondrial dysfunction observed in post-ischemic pathology. We
      investigated the effect of intra-carotid infusion of 5-10 mg/kg of cyclosporin A
      (CsA) on the neuronal survival in CA1 sector of hippocampus and on the
      subcellular localization of cytochrome C in the model of 5 min gerbil brain
      ischemia. To discriminate between the immunosuppressive and the mitochondria
      protecting component of CsA action, we compared the effect of CsA with one other
      immunosuppressant FK506. Almost 75% of neurons in ischemia-affected brain area
      were saved after CsA but not after FK506 treatment. This protective effect was
      only observed when the drug was infused immediately upon reperfusion. Early CsA
      treatment was able to block an initial phase of cytochrome C release, occurring
      transiently at 30 min post-ischemia, an effect never observed after FK506
      administration. We assessed the neuroprotective potency of CsA vs. FK506 in rat
      cortical primary culture treated with compounds that mimic destructive signals
      induced by brain ischemia. In all cases, neuronal death and cytochrome C release
      were evidently suppressed by CsA applied not later than 30 min after the initial
      insult. Thus, early treatment with CsA in vitro and after bolus intra-carotid
      injection in vivo can save neurons by inhibition of cytochrome C efflux to
      cytoplasm.

PMID- 14969737
TI  - Expression of the ionotropic glutamate receptor subunits and NMDA receptor
      associated intracellular proteins in the substantia nigra in schizophrenia.
AB  - Multiple neurotransmitter systems have been implicated in the pathophysiology of
      schizophrenia. Dopamine hyperactivity has often been implicated in this illness.
      More recently, the glutamate hypothesis of schizophrenia suggests that NMDA
      receptor (NMDAR) hypofunction may also play a role in this illness. This is based
      primarily on studies showing that phencyclidine, an NMDAR antagonist, can induce
      a schizophreniform psychosis. While NMDAR dysfunction is most often implicated in
      schizophrenia, other components of the glutamate system, such as the AMPA and
      kainate receptors, as well as NMDAR-associated intracellular proteins, may also
      play a role in regulating NMDA receptor activity and glutamate neurotransmission.
      There is growing interest in the hypothesis that the pathophysiology of
      schizophrenia involves alterations in dopamine-glutamate interactions. The
      glutamate system is anatomically and functionally linked to the dopamine system,
      and glutamate can modulate dopaminergic activity and release by stimulating
      various glutamate receptor subtypes expressed by dopaminergic neurons in the
      substantia nigra/ventral tegmental area. In this study, we investigated dopamine
      glutamate interactions by measuring the expression of transcripts encoding the
      subunits for the ionotropic glutamate receptors (NMDA, AMPA and kainate) and five
      NMDAR-associated intracellular proteins, PSD-93, PSD-95, SAP102, NF-L and yotiao
      in the dopaminergic neurons in the substantia nigra pars compacta (SNc) of
      subjects with schizophrenia and a comparison group. Tyrosine hydroxylase (TH, a
      marker of dopamine-synthesizing cells), NR1 (an NMDA receptor subunit) and GluR5
      (a kainate subunit) transcript levels were significantly increased in the SNc in
      schizophrenia. These data support the hypothesis that schizophrenia may involve
      alterations in dopamine-glutamate interactions.

PMID- 14969738
TI  - Cloning and developmental expression of Shaker potassium channels in the cochlea
      of the chicken.
AB  - Signal coding by the receptor and neuronal cells of the auditory system involves
      various ion channels that modulate a sound stimulus. The genes that encode a
      number of these ion channels and their accessory subunits are presently unknown
      for channels found in the sensory epithelium and cochlear nerve. Among these
      genes are those that encode delayed rectifier and transient type potassium
      channels found in both the sensory cells and the ganglion. Here, we report the
      cloning and developmental expression of Shaker family members that include
      cKv1.2, cKv1.3, cKv1.5, and the Shaker-related cGMP-gated potassium channel
      cKCNA10. Clones were obtained by screening a chicken embryonic cochlea cDNA
      library using, as a probe, a mixture of two DNA fragments of cKv1.2 and cKv1.3
      obtained by the reverse transcription polymerase chain reaction (RT-PCR).
      Sequence analysis revealed chicken homologues of Kv1.2, Kv1.3, Kv1.5 and cGMP
      gated potassium channels with a deduced amino acid homology of 96-98%, 82-84%, 67
      71% and 67-79% to correspondent mammalian homologues. During development of
      chicken inner ear, RT-PCR studies show expression of cKv1.2, cKv1.3 and cKv1.5 as
      early as Embryonic Day (ED) 3, while cKCNA10 was detected at low levels beginning
      on ED6 and was highly expressed by ED9. Additionally, analysis of expression in
      different parts of the cochlea showed that these genes were co-expressed in
      different regions of the cochlea, including the cochlear ganglion, sensory
      epithelium, lagena, and tegmentum. This expression pattern suggests the potential
      for the formation of heteromeric channels from the corresponding alpha-subunits
      in these various tissues.

PMID- 14969739
TI  - Latency to onset of status epilepticus determines molecular mechanisms of seizure
      induced cell death.
AB  - The molecular mechanisms mediating degeneration in response to neuronal insults,
      including damage evoked by prolonged seizure activity, show substantial
      variability across laboratories and injury models. Here we investigate the extent
      to which the proportion of cell death occurring by apoptotic vs. necrotic
      mechanisms may be shifted by changing the temporal parameters of the insult. In
      initial studies with continuous seizures (status epilepticus, SE), signs of
      apoptotic degeneration were most clearly observed when SE occurred following a
      long latency (>86 min) after injection of kainic acid as compared with a short
      latency SE (<76 min). Therefore, in this study we directly compared short- with
      long-latency SE for the expression of molecular markers for apoptosis and
      necrosis in an especially vulnerable brain region (rhinal cortex). Molecular
      markers of apoptosis (DNA fragmentation, cleavage of ICAD, an inhibitor of
      "caspase-activated DNase" (CAD), and prevalence of a caspase-generated fragment
      of alpha-spectrin) were detected following long-latency SE. Short-latency SE
      resulted in expression of predominantly necrotic features of cell death, such as
      "non-ladder" pattern of genomic DNA degradation, prevalence of a calpain
      generated alpha-spectrin fragment, and absence of ICAD cleavage. Silver staining
      revealed no significant difference in the extent and spatial distribution of
      degeneration between long- or short-latency SE. These data indicate that the
      latency to onset of SE determines the extent to which apoptotic or necrotic
      mechanisms contribute to the degeneration following SE. The presence of a long
      latency period, during which multiple brief seizure episodes may occur, favors
      the occurrence of apoptotic cell death. It is possible that the absence of such
      "preconditioning" period in short-latency SE favors predominantly necrotic
      profile.

PMID- 14969740
TI  - Differential involvement and heterogeneous phosphorylation of tau isoforms in
      progressive supranuclear palsy.
AB  - We found previously that aggregated insoluble tau protein in progressive
      supranuclear palsy (PSP) brains exhibits a heterogeneous pattern that is not
      segregated by the type of clinical presentation. Here we have investigated tau
      isoform composition from 20 PSP cases and found marked variation between
      different brains. Cases were classified into three groups, each comprising
      essentially of (1) 1N4R; (2) 1N4R and 1N3R; or (3) 1N4R, 1N3R and 0N4R tau
      isoforms. There was also an absence of a simple relationship between isoform
      composition and the pattern of insoluble tau before dephosphorylation. We
      conclude that there is distinct molecular heterogeneity in the involvement of tau
      isoforms in the tau pathology in PSP.

PMID- 14969741
TI  - Application of a customized pathway-focused microarray for gene expression
      profiling of cellular homeostasis upon exposure to nicotine in PC12 cells.
AB  - Maintenance of cellular homeostasis is integral to appropriate regulation of
      cellular signaling and cell growth and division. In this study, we report the
      development and quality assessment of a pathway-focused microarray comprising
      genes involved in cellular homeostasis. Since nicotine is known to have highly
      modulatory effects on the intracellular calcium homeostasis, we therefore tested
      the applicability of the homeostatic pathway-focused microarray on the gene
      expression in PC-12 cells treated with 1 mM nicotine for 48 h relative to the
      untreated control cells. We first provided a detailed description of the focused
      array with respect to its gene and pathway content and then assessed the array
      quality using a robust regression procedure that allows for the exclusion of
      unreliable measurements while decreasing the number of false positives. As a
      result, the mean correlation coefficient between duplicate measurements of the
      arrays used in this study (control vs. nicotine treatment, three samples each)
      has increased from 0.974+/-0.017 to 0.995+/-0.002. Furthermore, we found that
      nicotine affected various structural and signaling components of the AKT/PKB
      signaling pathway and protein synthesis and degradation processes in PC-12 cells.
      Since modulation of intracellular calcium concentrations ([Ca(2+)](i)) and
      phosphatidylinositol signaling are important in various biological processes such
      as neurotransmitter release and tissue pathogenesis including tumor formation, we
      expect that the homeostatic pathway-focused microarray potentially can be used
      for the identification of unique gene expression profiles in comparative studies
      of drugs of abuse and diverse environmental stimuli, such as starvation and
      oxidative stress.

PMID- 14969742
TI  - Decreased immunodensities of micro-opioid receptors, receptor kinases GRK 2/6 and
      beta-arrestin-2 in postmortem brains of opiate addicts.
AB  - The homologous regulation of opioid receptors, through G protein-coupled receptor
      kinases (GRKs) and beta-arrestins, is an initial step in the complex molecular
      mechanisms leading to opiate tolerance and dependence. This study was designed to
      evaluate in parallel the contents of immunolabeled micro-opioid receptors
      (glycosylated proteins), two representative GRKs (GRK 2 and GRK 6) and beta
      arrestin-2 in brains of opiate addicts who had died of an opiate overdose (heroin
      or methadone). The immunodensities of micro-opioid receptors were decreased (66
      kDa protein: 24%, n=24, P<0.0001; 85 kDa protein: 16%, n=24, P<0.05) in the
      prefrontal cortex of opiate addicts compared with sex-, age-, and PMD-matched
      controls. This down-regulation of brain micro-opioid receptors was more
      pronounced in opiate addicts dying of a heroin overdose (27-30%, n=13) than in
      those who died of a methadone overdose (5-16%, n=11). In the same brains,
      significant decreases in the immunodensities of GRK 2 (19%, n=24, P<0.05), GRK 6
      (25%, n=24, P<0.002) and beta-arrestin-2 (22%, n=24, P< 0.0005) were also
      quantitated. In contrast, the content of alpha-internexin (a neuronal marker used
      as a negative control) was not changed in brains of opiate addicts. In these
      subjects, there was a significant correlation between the densities of GRK 6 and
      beta-arrestin-2 (r=0.63, n=24, P=0.001), suggesting that both proteins are
      regulated in a coordinated manner by opiate drugs in the brain. The results
      indicate that opiate addiction in humans (tolerant state) is associated with down
      regulation of brain micro-opioid receptors and regulatory GRK 2/6 and beta
      arrestin-2 proteins. These molecular adaptations may be relevant mechanisms for
      the induction of opiate tolerance in brains of opiate addicts.

PMID- 14969743
TI  - mu-Opioid receptor knockout mice display reduced cocaine conditioned place
      preference but enhanced sensitization of cocaine-induced locomotion.
AB  - The mu-opioid receptor (OPRM1) is expressed in brain regions implicated in reward
      and locomotor processes. Reduced reward, not only from opiates, but also from
      several other abused substances has been observed in mice with lifelong deletions
      of the OPRM1 gene. To further define the roles of mu-opioid receptors in
      psychostimulant actions, cocaine psychomotor stimulant and rewarding effects were
      examined in wild-type (WT), heterozygous and homozygous mu-opioid receptor
      knockout mice. While mu-opioid receptor knockout did not affect basal locomotion,
      locomotor stimulant effects of cocaine were enhanced in a within-subjects dose
      response experiment. However, further study revealed that in mice injected with
      20 mg/kg for the first time, there was no difference in the locomotor-stimulating
      effects of cocaine between knockout and wild-type mice. In a sensitization study
      (modeled after the conditions in the dose-response experiment) although not
      observed in WT mice, OPRM1-/- mice did exhibit cocaine sensitization. By stark
      contrast, and similar to the effects of other rewarding drugs in OPRM1 KO mice,
      cocaine reward, as assessed by conditioned place preference, was reduced in both
      homozygous and heterozygous OPRM1 KO mice. The present results confirm a central
      role of the mu-opioid receptor in drug reward but opposing effects on locomotor
      sensitization. The reduced cocaine reward identified in heterozygous mu-opioid
      receptor knockout mice supports the possibility that humans with fewer available
      mu-opioid receptors might experience less cocaine reward.

PMID- 14969744
TI  - Muscarinic acetylcholine receptor stimulation induces expression of the activity
      regulated cytoskeleton-associated gene (ARC).
AB  - Muscarinic acetylcholine receptors (mAChR) are involved in learning and memory
      but their molecular function in these processes is not fully understood. In this
      study, the signal transduction pathway coupling mAChR activation to induction of
      the activity-regulated cytoskeleton-associated gene (ARC) was examined. ARC was
      first identified as an effector immediate early gene induced by neuronal activity
      and ARC protein is thought to play a role in synaptic plasticity. In rats,
      intraperitoneal injection of pilocarpine, a potent agonist of mAChR, led to
      increased ARC expression in the brain. In human SH-SY5Y neuroblastoma cells mAChR
      stimulation with carbachol caused a rapid and robust induction of ARC expression.
      This effect was inhibited by atropine, a nonselective muscarinic receptor
      antagonist as well as by M1/M3 subtype-specific antagonists. Analysis of mAChR
      downstream effectors revealed that protein kinase C (PKC) and tyrosine kinases of
      the src family are key molecules in the signal cascade leading to ARC expression.
      Our data suggest, for the first time, that a correlation exists among mAChR
      controlled signal cascades, the induction of the effector immediate early gene
      ARC and synaptic plasticity.

PMID- 14969745
TI  - The TP53-ARF tumor suppressor pathway is frequently disrupted in large/cell
      anaplastic medulloblastoma.
AB  - We analyzed the TP53 and INK4A/ARF loci in 29 pediatric medulloblastomas.
      Mutually exclusive mutation in TP53, methylation of P14(ARF) or deletion of
      INK4A/ARF were identified in 21% (6/29) of tumors. Five of these alterations were
      detected in large cell/anaplastic medulloblastomas or tumors with significant
      anaplasia. Our data provide the first evidence that alterations within the TP53
      ARF tumor suppressor pathway contribute to development of aggressive forms of
      medulloblastoma.

PMID- 14969746
TI  - A single-chain Fv intrabody provides functional protection against the effects of
      mutant protein in an organotypic slice culture model of Huntington's disease.
AB  - Huntington's disease (HD) is a progressive, hereditary, neurodegenerative
      disorder caused by an expanded polyglutamine tract in huntingtin protein, leading
      to misfolding and abnormal protein-protein interactions. Reducing the initial
      misfolding should lead to decreased pathogenesis. We show that malonate stress
      increases the number of dead or dying cells when organotypic slice cultures are
      transduced to express pathological-length huntingtin fragments. Co-transfected
      anti-HD single-chain Fv (sFv) intrabodies can reverse this HD-specific increase
      in malonate-induced morbidity.

PMID- 14969747
TI  - Transforming growth factor beta receptor family ligands inhibit hepatocyte growth
      factor synthesis and secretion from astrocytoma cells.
AB  - Transforming growth factor beta (TGFbeta) and hepatocyte growth factor (HGF)
      promote glioma progression. Using U87human astrocytoma cells, which express
      TGFbeta receptors (TbetaRs), we show (1) mRNA expression of Smads (2, 3, 4), bone
      morphogenetic protein (BMP)- and activin-A receptors; (2) TGFbeta1 inhibits and
      HGF induces proliferation; (3) TGFbeta1 and activin-A equipotently inhibit HGF
      secretion more than BMP-2, but none alters c-Met expression. Because interfering
      with TbetaR signaling might nullify the beneficial inhibition of HGF secretion,
      activin-A should instead be considered for combination glioma therapy.

PMID- 14969748
TI  - Controlled secretion of beta-endorphin from human embryonic kidney cells carrying
      a Tet-on-beta-endorphin fusion gene.
AB  - To create a cell line with controlled and specific secretion of beta-endorphin, a
      new fusion gene was constructed by joining human beta-endorphin coding sequence
      to part of NL1 gene. HEK293 cells carrying Tet-on system transfected with this
      fusion gene secreted beta-endorphin in a dose-dependent manner upon doxycycline
      administration. These findings suggest that this system can direct the controlled
      secretion of any peptide hormones such as beta-endorphin.

PMID- 14969749
TI  - Lectins and glycoconjugates in drug delivery and targeting.

PMID- 14969750
TI  - The sugar code in drug delivery.

PMID- 14969751
TI  - Lectin-mediated drug targeting: history and applications.
AB  - The purpose of this paper is to review the history of using lectins to target and
      deliver drugs to their site of action. The hour of birth of "lectinology" may be
      defined as the description of the agglutinating properties of ricin, by Herrmann
      Stillmark in 1888, however, the modern era of lectinology began almost 100 years
      later in 1972 with the purification of different plant lectins by Sharon and Lis.
      The idea to use lectins for drug delivery came in 1988 from Woodley and Naisbett,
      who proposed the use of tomato lectin (TL) to target the luminal surface of the
      small intestine. Besides the targeting to specific cells, the lectin-sugar
      interaction can also been used to trigger vesicular transport into or across
      epithelial cells. The concept of bioadhesion via lectins may be applied not only
      for the GI tract but also for other biological barriers like the nasal mucosa,
      the lung, the buccal cavity, the eye and the blood-brain barrier.

PMID- 14969752
TI  - Computational modeling of the sugar-lectin interaction.
AB  - In the last few years numerous experimental studies have shed light onto the
      details of the lectin-carbohydrate interaction. X-ray crystallography and NMR
      spectroscopy have been used to elucidate the structures of lectins, sugars, and
      their complexes. In addition, an increasing number of experimental methods has
      been employed to determine the thermodynamic and kinetic parameters of the
      binding process. Based on this experimental data, computational methods have been
      developed to model and predict these interactions. A plethora of techniques from
      Molecular Modeling and Computational Chemistry have been applied to the problem
      and current models achieve high-quality predictions. These successes are based on
      both new theoretical approaches and reliable experimental data. The aim of the
      present article is to outline the most relevant computational and experimental
      methods applied in the field of lectin-carbohydrate interaction and to give an
      overview of the current state of the art in the modeling of these interactions
      with a focus on plant lectins.

PMID- 14969753
TI  - The lectin-cell interaction and its implications to intestinal lectin-mediated
      drug delivery.
AB  - Based on the fact that oligosaccharides encode biological information, the
      biorecognition between lectinised drug delivery systems and glycosylated
      structures in the intestine can be exploited for improved peroral therapy. Basic
      research revealed that some lectins can mediate mucoadhesion, cytoadhesion, and
      cytoinvasion of drugs. Entering the vesicular pathway by receptor mediated
      endocytosis, part of the conjugated drug is accumulated within the lysosomes.
      Additionally, part of the drug is supposed to be transported across the
      epithelium. Moreover, factors probably adversely influencing feasibility of the
      concept such as toxicity, immunogenicity, and intestinal stability of plant
      lectins are discussed. As exemplified by lectin-grafted prodrug and carrier
      systems, this strategy is expected to improve absorption and probably
      bioavailability of poorly absorbable drugs, peptides and proteins as well as
      therapeutic DNA.

PMID- 14969754
TI  - Lectin-mediated drug delivery in the oral cavity.
AB  - The delivery of therapeutic agents to, or via, the oral cavity is limited by the
      efficient removal mechanisms that exist in this area. Lectins are proteins or
      glycoproteins that bind to specific sugar residues, and can, therefore, interact
      with the glycoconjugates present on cell surfaces or salivary mucins. Endogenous
      lectins could also be used as points of attachment for carbohydrate-containing
      delivery systems. This review considers the possibility of using lectins as
      targeting agents within the oral cavity and reports on some of the limited number
      of studies completed to date. As lectins are multifunctional molecules, the
      possibility of using them as both targeting and therapeutic agents is considered.
      Lectin-containing delivery systems are a potential innovation for targeted and
      prolonged therapy within the oral cavity, but considerations such as toxicity and
      cost will need to be addressed before their routine use becomes a reality.

PMID- 14969755
TI  - Drug targeting to the colon with lectins and neoglycoconjugates.
AB  - Targeting of drugs to specific sites of action provides several advantages over
      non-targeted drugs. These include the prevention of side effects of drugs on
      healthy tissues and enhancement of drug uptake by targeted cells. This review
      will cover traditional approaches of colon drug targeting as well as the use of
      lectins and neoglycoconjugates for the targeted delivery. Direct and reverse
      targeting strategies, potential molecular targets and targeting moieties for
      colon drug delivery, targeted drug delivery systems (DDS) for colon delivery,
      anticancer DDS targeted to colon cancer are examined. Directions of future
      development are discussed.

PMID- 14969756
TI  - M cell targeting by lectins: a strategy for mucosal vaccination and drug
      delivery.
AB  - Bioadhesins are a recognised method of enhancing the absorption of drugs and
      vaccines at mucosal surfaces. Additionally, bioadhesins allow for cell specific
      targeting. Lectin-mediated targeting and delivery exploits unique surface
      carbohydrates on mucosal epithelial cells. The antigen-sampling M cells offer a
      portal for absorption of colloidal and particulate delivery vehicles, including
      bacteria, viruses and inert microparticles. We review work supporting the use of
      lectins to aid targeting to intestinal M cells. Consideration is also given to
      lectin-mediated targeting in non-intestinal sites and to the potential
      application of other bioadhesins to enhance M cell transport. While substantial
      hurdles must be overcome before mucosal bioadhesins can guarantee consistent,
      safe, effective mucosal delivery, this strategy offers novel opportunities for
      drug and vaccine formulation.

PMID- 14969757
TI  - Selectins-an emerging target for drug delivery.
AB  - Selectins are multifunctional adhesion molecules that mediate the initial
      interactions between circulating leukocytes and cells of 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. Of
      late, selectins were introduced as targets for drug delivery in the development
      of new anti-inflammatory therapeutics and in anti-cancer therapy. This review
      will examine the selectins and their ligands with a focus on recent findings on
      their role in physiology and pathophysiology as well as the emerging role of
      selectins as targets in controlled drug delivery.

PMID- 14969764
TI  - Antigen presentation and immune regulatory capacity of immature and mature
      enriched antigen presenting (dendritic) cells derived from human bone marrow.
AB  - Several reports including those from this laboratory have demonstrated that bone
      marrow cells (BMC) downregulate in vitro both mixed leukocyte reaction and
      cytotoxic T lymphocyte reactions. We consequently hypothesized that a general
      property of immature cells of hematopoietic organs is their ability to suppress
      immune reactivity. As one of these suppressive activities, the lack of
      costimulatory molecules was proposed as a mechanism by which immature antigen
      presenting cells of the bone marrow might be involved. In the present report, we
      used two culture environments, each of which would regulate a different
      maturation pattern of human bone marrow-derived enriched dendritic antigen
      presenting cells (DC or APC) to determine the respective effects on in vitro
      immune regulatory function. Human BMC depleted of CD3+ cells were cultured with
      either: interleukin-4 (IL-4) and granulocyte macrophage-colony stimulating factor
      (GM-CSF), to maintain DC-enriched populations in an immature state (iAPC); or an
      interferon-gamma (IFNgamma), tumor necrosis factor alpha (TNF-alpha), GM-CSF,
      LPS, and IL-6 cocktail to promote the maturation of DC-enriched APC (mAPC). These
      iAPC and mAPC were, respectively, phenotypically characterized and also tested in
      vitro for the following: (1) both direct and indirect-antigen presentation
      functions; (2) immune regulatory functions on the response of autologous and
      allogeneic peripheral blood lymphocytes (PBL); and (3) Western blot analysis
      determining the levels of both major histocompatibility complex (MHC) class I
      related cytoplasmic transporter molecules associated with antigen processing
      (TAP1) and as well as proteasome activator molecules (PA28alpha). The iAPC
      population expressed fewer dendritic cell markers (CD83 and DCsign), and
      costimulator molecules (CD86 and CD40) than the mAPC, such that there was an
      approximate threefold increase in expression of CD83, 2.5-fold increase in
      DCsign, and a threefold increase in CD40 and CD86 on mAPC than on iAPC (p=0.005
      for CD83; p=0.001 for DCsign; p=0.001 for CD86; and p=0.001 for CD40). In
      lymphoproliferative assays, indirect and direct alloantigen presentation by iAPC
      was weaker than by mAPC (p=0.05 and 0.04). In addition, iAPC were able to
      downregulate allogeneic CTL responses. Also, after pulsing with Epstein-Barr
      virus (EBV) protein antigens, the iAPC were less efficient in their presentation
      to autologous EBV-specific T-cell lines, and caused an inhibition of EBV-CTL
      generation. The expression of TAP1 and PA28alpha was reduced in iAPC in
      comparison to mAPC. These findings support the notion that a maturation state of
      BMC-derived APC correlates with their capacity to present antigen. The observed
      in vitro deficiency of this function by immature bone marrow cells may therefore
      contribute to the immune downregulatory capacity seen in the BMC compartment.

PMID- 14969765
TI  - Identification and characterization of intestinal Peyer's patch interferon-alpha
      producing (plasmacytoid) dendritic cells.
AB  - Recently, a subset of murine dendritic cells (DC) has been identified that
      resembles human plasmacytoid (pDC) the principal interferon-alpha (IFN-alpha)
      producing cells in blood. In this study, C57BL/10 (B10;H2b) mice were treated
      with fms-like tyrosine 3 kinase Ligand (Flt3L; 10 microg/d; i.p.; 10 days) that
      expands DC selectively in vivo. Putative pDC (CD11c+B220+) were identified in the
      subepithelial dome and in interfollicular regions of intestinal Peyer's patches
      (PP) from both normal and Flt3L-treated animals. Freshly-isolated, immunobead
      purified CD11c+ DC from PP were flow-sorted to obtain lineage- (CD11b-CD19-)
      CD11c+ B220+ DC (purity>96%). Flow cytometric analysis revealed that these sorted
      PPpDC were negative for surface markers associated with myeloid DC (CD11b) and
      expressed only low levels of the "lymphoid-related" DC marker CD8alphaalpha+.
      They expressed low levels of costimulatory molecules and moderate MHC class II.
      They proved weak stimulators of naive allogeneic (C3H; H2k) T-cell proliferation.
      Cytospin preparations of sorted CD11c+B220+ cells revealed plasmacytoid
      morphology similar to that of human pDC. Immunocytochemistry and enzyme
      immunoassay revealed that, within 24-hour culture with Herpes simplex virus (10
      p.f.u./cell), a subpopulation of stimulated (but not unstimulated) CD11c+B220+ DC
      produced and secreted IFN-alpha. This novel DC subset may play important roles in
      innate and adaptive immune responses of the gut and in the regulation of mucosal
      immune reactions.

PMID- 14969766
TI  - Cell surface expression of MHC class I antigen is suppressed in indoleamine 2,3
      dioxygenase genetically modified keratinocytes: implications in allogeneic skin
      substitute engraftment.
AB  - Indoleamine 2,3-dioxygenase (IDO) has been indicated to prevent the fetus from
      maternal T-cell rejection. A longer survival of IDO genetically modified islets
      transplanted into NOD mouse kidney capsules has also been demonstrated. As IDO
      mediated mechanism of graft protection has not been elucidated, in our study we
      hypothesize that the expression of IDO may prevent immune rejection by
      suppressing the major histocompatibility complex (MHC) class I antigen. To test
      this hypothesis, an IDO adenoviral vector was constructed and the effect of IDO
      on MHC class I expression was evaluated on recombinant adenoviral transfected
      keratinocytes. Following a successful construction of IDO expressing adenoviral
      vector, the catabolic activity of IDO enzyme was evaluated by measuring the
      levels of its product, kynurenine in keratinocyte conditioned medium. The results
      indicated a higher level of kynurenine in IDO expressing cells relative to those
      of control cells. The results of MHC class I experiments revealed a significant
      downregulation of cell membrane associated MHC class I antigen in IDO genetically
      modified keratinocytes relative to that of either nontransfected or empty vector
      transfected cells. Further experiments demonstrated that an addition of
      tryptophan or IDO inhibitor markedly restored the expression of MHC class I on
      IDO transfected keratinocytes. The findings of this study suggest that
      downregulation of MHC class I expression by IDO might be one of the mechanisms
      through which IDO mediates local immunosuppression.

PMID- 14969767
TI  - T-cell autoreactivity to Hsp in human transplantation may involve both
      proinflammatory and regulatory functions.
AB  - Heat shock proteins (Hsp) are moving from the category of basically intracellular
      chaperone molecules to important proteins in both innate and acquired immune
      responses, with great potential for clinical application as immunomodulators.
      Both proinflammatory and regulatory Hsp-reactive T cells have been described in
      animal models of autoimmune diseases. To investigate the role of autoreactivity
      to Hsp60 and Hsp70 in human transplantation, we analyzed, sequentially,
      peripheral blood mononuclear cell proliferation and cytokine production before
      and at different time points after renal transplantation, as well as the
      modulation of proliferation to Hsp in the presence of exogenous cytokines.
      Proliferation to Hsp60 and Hsp70 in the pretransplantation (pre-Tx) period was
      significantly associated with rejection episodes in the first months post-Tx. In
      contrast, IL-4 production was significantly associated with absence of rejection.
      Addition of exogenous IL-4 distinctly modulated the proliferative response to
      Hsp60; inhibiting proliferation in 83% of patients in the early post-Tx period (0
      6 months), in which rejection episodes occurred, and inducing proliferation in
      62.5% of patients in the later period (>12-24 months), when no rejection was
      observed. Characterization of autoreactive anti-Hsp60 regulatory T cells may
      permit new approaches to control the proinflammatory response to the graft, as
      well as aggressive autoimmunity.

PMID- 14969768
TI  - Th2/Th3 cytokine genotypes are associated with pregnancy loss.
AB  - Cytokines are critical immunoregulatory molecules, responsible for determining
      the nature of an immune response. It has been proposed that Th2/Th3 immune
      reactions support normal pregnancy, while Th1 immunity is considered detrimental
      to the fetus. Since cytokine production is partly under genetic control, it is
      possible that women suffering from a high incidence of abortions are genetically
      predisposed to mount a type of immune response inappropriate for pregnancy
      maintenance. This study investigated the frequencies of cytokine gene
      polymorphisms in abortion-prone women and women with successful pregnancies. We
      investigated the role of Th1/Th2/Th3 cytokine gene polymorphisms, such as TGF
      beta1 codon 10 (TGFbetac10; C to T), TGF-beta1 codon 25 (TGFbetac25; G to C),
      TNFalpha promoter-308 (G to A), IL-6 promoter-174 (G to C), IL-10 promoter-1082
      (G to A), IL-10 promoter-819 (C to T), IL-10 promoter-592 (C to A), and IFNgamma
      intron 1 +874 (A to T) in abortion-prone female patients. Our results support the
      importance of Th2/Th3 immune responses in pregnancy loss, and suggest that an
      individual's immunogenetic profile indicative of imbalances in Th2/Th3 cytokines
      is associated with pregnancy loss. Our results suggest that abortive events are
      determined by genetic factors, reflected in the female patient's immunogenetic
      profile.

PMID- 14969769
TI  - Nonantigen specific CD8+ T suppressor lymphocytes originate from CD8+CD28- T
      cells and inhibit both T-cell proliferation and CTL function.
AB  - Nonantigen specific CD8+ suppressor T lymphocytes (CD8+ Ts) inhibit T-cell
      proliferation of antigen-specific T lymphocytes. The impossibility to generate in
      vitro these cells has been correlated with the appearance of relapses in patients
      affected by autoimmune diseases, suggesting the involvement of these cells in
      immune regulation. This study was aimed to identify circulating precursors and to
      characterize the phenotype and mechanism of action of CD8+ Ts. We found that CD8+
      Ts can be generated in vitro from CD8+CD28- T lymphocytes, but not from CD8+CD28+
      T cells. A key role in their generation is played by monocytes that secrete
      interleukin-10 (IL-10) after granulocyte macrophage-colony-stimulating factor (GM
      CSF) stimulation. Cell-to-cell direct interaction between CD8+CD28- T cells and
      monocytes does not play a role in the generation of CD8+ Ts. CD8+ Ts have a
      CD45RA+, CD27-, CCR7-, IL-10Ralpha+ phenotype and a TCR Vbeta chain repertoire
      overlapping that of autologous circulating CD8+ T cells. This phenotype is
      typical of T lymphocytes previously expanded due to antigen stimulation. Their
      suppressive effect on T-cell proliferation targets both antigen presenting cells,
      such as dendritic cells, and antigen-specific T lymphocytes, and is mediated by
      IL-10. CD8+ Ts suppress also the antigen-specific cytotoxic activity of CTL
      decreasing the expression of HLA class I molecules on target cells through IL-10
      secretion. These findings can be helpful for the better understanding of immune
      regulatory circuits and for the definition of new pathogenic aspects in
      autoimmunity and tumor immunology.

PMID- 14969770
TI  - The 4H84 monoclonal antibody detecting beta2m free nonclassical HLA-G molecules
      also binds to free heavy chains of classical HLA class I antigens present on
      activated lymphocytes.
AB  - We have found that 4H84 monoclonal antibody (mAb) used for detection of beta2m
      free HLA-G molecules also binds to free heavy chains of classical HLA class I
      antigens generated on the cell surface by mild acid treatment. Here we
      demonstrate that beta2m free classical HLA class I molecules induced on the
      surface of activated lymphocytes not expressing HLA-G also bind 4H84 mAb. These
      results demonstrate that 4H84 mAb should be used for detection of HLA-G in cells
      and tissues with backing by other HLA-G specific mAbs.

PMID- 14969771
TI  - HLA class II DRB high resolution genotyping by pyrosequencing: comparison of
      group specific PCR and pyrosequencing primers.
AB  - Sequencing of alleles of the highly polymorphic, multiple loci HLA-DRB gene
      family was performed by pyrosequencing using purified DNA from the 11(th)
      International Histocompatibility Workshop human lymphoblastiod cell lines as well
      as genomic DNA isolated from blood samples obtained from healthy adult
      volunteers. Genomic DNA was prepared from donors whose blood had been stored
      either frozen or as dried blood spots. Pyrosequence-based typing was optimized
      for identifying alleles of the HLA-DRB1, -3, -4, and -5 genes. The procedure
      should be applicable to other HLA loci including the class I genes HLA-A and -B
      that, along with HLA-DRB, are crucial for histocompatibility matching of tissue
      antigens during transplantation. Computer simulation of pyrosequencing data
      suggest that alleles of HLA-DRB1, -3, -4, and -5 were readily identifiable by
      pyrosequencing as were their heterozygous allelic combinations. Pyrosequencing
      primers were designed to specifically sequence HLA loci of interest even in a
      background of other amplified, closely related sequences such as alleles of the
      pseudogene HLA-DRB6, -7, -8, and -9. Polymorphic residues of HLA-DRB genes were
      identified within each pyrosequencing reaction, obtained by 50 to 70 nucleotide
      read lengths. Heterozygous allelic combinations of HLA genes were analyzed and
      compared successfully to genotyping of alleles by sequence-specific
      oligonucleotide probe hybridization as well as allele specific polymerase chain
      reaction protocols. Pyrosequence-based typing is compatible with genotyping of
      allelic combinations expected from heterozygous individuals, resulting in
      nucleotide resolution of the highly polymorphic HLA system. Using a single
      pyrosequence instrument, complete typing of HLA-DRB genes can be performed daily
      on hundreds of individuals for high resolution histocompatibility genotyping
      studies.

PMID- 14969772
TI  - HLA-A*2402 and a microsatellite (D6S248) are secondary independent susceptibility
      markers to ankylosing spondylitis in Basque patients.
AB  - Ankylosing spondylitis (AS) is universally associated with human leukocyte
      antigen B27 (HLA-B27), although other genes could determine the development and
      clinical expression of the disease. HLA-A9 (A*2402) allele was previously found
      to be associated in Basque patients. The objective of this study is to perform a
      more precise analysis of microsatellite polymorphisms in HLA-A*2402 and B27
      haplotypes to elucidate the significance of this association. A group of 50
      unrelated AS patients and 113 controls of Basque origin were studied. Eight
      microsatellites in the class I major histocompatibility complex region with
      vicinity to HLA-A and -B were analyzed and the strength of allelic associations
      to AS and linkage disequilibrium (LD) between alleles were evaluated. Allele 15
      at the microsatellite locus D6S248, 1000 Kb telomeric to HLA-A showed a strong
      positive association with the disease (OR:6; pc=4.7x10(-4)) and it could not be
      explained by LD to HLA-B27, HLA-A*2402 or any other loci. We found that D6S248-15
      allele together with HLA-A*2402 could be B27-independent markers of additional
      susceptibility gene/s localised in the region telomeric to HLA-A in Basque AS
      patients.

PMID- 14969773
TI  - HLA-Cw*0409N is associated with HLA-A*2301 and HLA-B*4403-carrying haplotypes.
AB  - The associations of HLA-B*4402 and HLA-B*4403 with alleles of HLA-A and HLA-Cw
      were investigated in panels of HLA-B*4403 and HLA-B*4402 homozygous individuals
      and in selected individuals carrying HLA-Cw*04 and HLA-B*4403. Some of these
      individuals were genotyped and also carried (HLA-DRB1*0701, DQB1*02). Among the
      latter, we studied individuals carrying the conserved extended haplotype (CEH)
      [HLA-Cw*04, B*4403, FC31, DRB1*0701, DQB1*02]. Four different common (HLA-Cw*,
      B*44) haplotypes were identified that extended to the HLA-A locus: HLA-A*0201,
      Cw*0501, B*4402; HLA-A*2902, Cw*1601, B*4403; HLA-A*2301, Cw*0401, B*4403; and
      HLA-A*2301, Cw*0409N, B*4403. We identified eight unrelated examples of the
      allele HLA-Cw*0409N. HLA-A*2301 was associated with both HLA-Cw*0401 and HLA
      Cw*0409N, suggesting that HLA-Cw*0409N may have arisen from a mutation in a CEH.
      We estimate that approximately 2 to 5 in 1000 Caucasian individuals carry the
      allele HLA-Cw*0409N, making it one of the most frequent null HLA alleles known to
      date. Our findings demonstrate the first example of three different HLA-Cw
      determined subtypes of a common or CEH carrying a shared HLA-B allele, in this
      case HLA-B*4403.

PMID- 14969774
TI  - The relation between social behavior and negative affect in psychosis-prone
      individuals: an experience sampling investigation.
AB  - Daily social behavior and negative affect were examined in a sample of
      individuals with a wide spectrum of psychosis-proneness scores. Using the
      experience sampling method, participants were signaled five times per day for a 1
      week period to provide naturalistic reports of location, activity, and social
      behavior. Little evidence was found for a direct association between psychosis
      proneness and specific behavioral profiles, but individuals with higher scores of
      psychosis-proneness reported spending more time doing nothing or waiting.
      However, the levels of anxious and depressed moods experienced in certain social
      and environmental contexts were also predicted by psychosis-proneness scores. The
      present results indicate that psychosis-proneness was associated with an increase
      in anxiety when individuals were with friends and an increase in depressed mood
      in daily task situations such as working or studying. By contrast, psychosis
      proneness predicted a decrease in depressed and anxious moods in other situations
      when the individual was not likely to be confronted by social contact with less
      known individuals, and lower anxious and depressed moods when in secure
      environments (in one's own home, home of family or friends). The implications of
      these findings are discussed in terms of understanding the expression of
      psychosis vulnerability and the potential reinforcement of maladaptive social
      behavior through operant conditioning mechanisms.

PMID- 14969775
TI  - Cross-sectional similarities and differences between schizophrenia,
      schizoaffective disorder and mania or mixed mania with mood-incongruent psychotic
      features.
AB  - BACKGROUND: The cross-sectional clinical differentiation of schizophrenia or
      schizoaffective disorder from mood-incongruent psychotic mania or mixed mania is
      difficult, since pathognomonic symptoms are lacking in these conditions. AIMS OF
      THE STUDY: To compare a series of clinical variables related to mood and
      cognition in patient groups with DSM-III-R diagnosis of schizophrenia,
      schizoaffective disorder, mood-incongruent psychotic mania and mood-incongruent
      psychotic mixed mania. METHODS: One hundred and fifty-one consecutive patients
      were evaluated in the week prior to discharge by using the structured clinical
      interview for DSM-III-R-patient edition (SCID-P). Severity of psychopathology was
      assessed by the 18-item version of the brief psychiatric rating scale (BPRS) and
      negative symptoms by the scale for assessment of negative symptoms (SANS). Level
      of insight was assessed with the scale to assess unawareness of mental disorders
      (SUMD). RESULTS: There were no differences in rates of specific types of
      delusions and hallucinations between subjects with schizophrenia, schizoaffective
      disorder, psychotic mania and psychotic mixed mania. SANS factors scores were
      significantly higher in patients with schizophrenia than in the bipolar groups.
      Patients with mixed state scored significantly higher on depression and
      excitement compared to schizophrenia group and, to a lesser extent, to
      schizoaffective group. Subjects with schizophrenia showed highest scores on the
      SUMD indicating that they were much more compromised on the insight dimension
      than subjects with psychotic mania or mixed mania. CONCLUSION: Negative rather
      than affective symptomatology may be a useful construct to differentiate between
      schizophrenia or schizoaffective disorders from mood-incongruent psychotic mania
      or mixed mania.

PMID- 14969776
TI  - Further evidence of the multi-dimensionality of hallucinatory predisposition:
      factor structure of a modified version of the Launay-Slade Hallucinations Scale
      in a normal sample.
AB  - Recent years has seen an increasing interest in the hallucinatory experience,
      including investigations of its phenomenological prevalence and character both in
      pathological and normal (predisposed) populations. We investigated the multi
      dimensionality of hallucinatory experiences in 265 subjects from the normal
      population, who completed a modified version of the Launay-Slade Hallucinations
      Scale. Principal components analysis was performed on the data. Four factors were
      obtained loading on items reflecting (1) sleep-related hallucinatory experiences
      (2) vivid daydreams (3) intrusive thoughts or realness of thought and (4)
      auditory hallucinations. The results offer further evidence of the multi
      dimensionality of hallucinatory disposition in the normal population. Directions
      for future research in hallucinatory predisposition are discussed.

PMID- 14969777
TI  - The deficit syndrome in schizophrenia: implications for the treatment of negative
      symptoms.
AB  - Schizophrenia psychopathology clusters around several symptom domains. One of
      these domains is negative symptomatology. We have defined the deficit syndrome as
      a disease entity characterized by the presence of primary enduring negative
      symptoms. A focus on primary negative symptoms demonstrates that deficit and
      nondeficit schizophrenia subgroups differ on clinical features, associated
      neuroimaging findings, neuropsychological and neurological measures, pattern of
      risk factors, and pharmacological response profiles. In the present article we
      focus on the importance of the distinction between primary and secondary negative
      symptoms for pathophysiology research. The development and mechanistic
      understanding of anti-negative symptom drugs may be informative regarding
      pathophysiology of primary negative symptoms. Although new antipsychotics are
      effective for secondary negative symptoms they have shown no efficacy for the
      deficit syndrome and new mechanisms of drug action appear to be required to
      address this aspect of the disease syndrome. The loss of precious human
      experiences and the association with poor long-term functional outcome justifies
      a focused and dedicated effort to discover the causes and treatments of this
      distinctive aspect of schizophrenia.

PMID- 14969778
TI  - Generalized anxiety disorder and major depressive disorder comorbidity: an
      example of genetic pleiotropy?
AB  - Generalized anxiety disorder (GAD) and major depressive disorder (MDD) are the
      most common type of anxiety-mood comorbidity. Up to 80% of subjects with lifetime
      GAD also have a comorbid mood disorder during their lifetime. Many hypotheses
      have been raised to explain such high comorbidity. Pleiotropy, i.e. a single
      genetic mutation explains (apparently) different disorders, is one of them and is
      hereby reviewed. Importance and reliability of GAD and MDD comorbidity (1);
      Evidence in favour of co-aggregation of GAD and MDD within families (the risk of
      one disorder in a proband increasing the risk for the other in relatives) (2);
      substantial heredity for both disorders according to twin studies with evidence
      for genetic correlation of unity between the two disorders (3); existence of
      numerous mechanisms (4) potentially linking the two disorders to common
      vulnerability genes, are all in accordance with such a hypothesis. Some examples
      of potentially shared mechanisms (such as CRF dysregulation or abnormal
      transcription factors) and possible common vulnerability genes (for example, the
      serotonin transporter gene) are given to highlight the pleiotropy hypothesis.

PMID- 14969779
TI  - The influence of temperament and character on functioning and aspects of
      psychological health among people with schizophrenia.
AB  - Research findings that link personality factors to functioning and symptoms in
      schizophrenia are inconsistent, and further studies are needed within the area.
      The purpose of this study was to investigate how personality, as measured by the
      Temperament and Character Inventory (TCI), was related to demographic factors,
      subtypes of diagnoses, level of functioning, and aspects of psychological health,
      including sense of coherence, perceived control, and self-esteem, among people
      with schizophrenia. Subjects were 104 individuals, aged 20-55 years, in
      psychiatric outpatient care. The results indicated that personality was not
      related to subtypes of diagnoses or demographic characteristics of the
      respondents, but to level of functioning and all aspects of psychological health.
      Especially self-directedness distinguished three groups of functioning and was
      highly correlated with the different aspects of psychological health. The article
      discusses how knowledge of schizophrenic patients' personality structure might be
      used for tailoring psychiatric treatments.

PMID- 14969780
TI  - Response-related fMRI of veridical and false recognition of words.
AB  - OBJECTIVES: Studies on the relation between local cerebral activation and
      retrieval success usually compared high and low performance conditions, and thus
      showed performance-related activation of different brain areas. Only a few
      studies directly compared signal intensities of different response categories
      during retrieval. During verbal recognition, we recently observed increased
      parieto-occipital activation related to false alarms. The present study intends
      to replicate and extend this observation by investigating common and differential
      activation by veridical and false recognition. METHODS: Fifteen healthy
      volunteers performed a verbal recognition paradigm using 160 learned target and
      160 new distractor words. The subjects had to indicate whether they had learned
      the word before or not. Echo-planar MRI of blood-oxygen-level-dependent signal
      changes was performed during this recognition task. Words were classified post
      hoc according to the subjects' responses, i.e. hits, false alarms, correct
      rejections and misses. Response-related fMRI-analysis was used to compare
      activation associated with the subjects' recognition success, i.e. signal
      intensities related to the presentation of words were compared by the above
      mentioned four response types. RESULTS: During recognition, all word categories
      showed increased bilateral activation of the inferior frontal gyrus, the inferior
      temporal gyrus, the occipital lobe and the brainstem in comparison with the
      control condition. Hits and false alarms activated several areas including the
      left medial and lateral parieto-occipital cortex in comparison with subjectively
      unknown items, i.e. correct rejections and misses. Hits showed more pronounced
      activation in the medial, false alarms in the lateral parts of the left parieto
      occipital cortex. CONCLUSIONS: Veridical and false recognition show common as
      well as different areas of cerebral activation in the left parieto-occipital
      lobe: increased activation of the medial parietal cortex by hits may correspond
      to true recognition, increased activation of the parieto-occipital cortex by
      false alarms may correspond to familiarity decisions. Further studies are needed
      to investigate the reasons for false decisions in healthy subjects and patients
      with memory problems.

PMID- 14969781
TI  - Dissociative disorders among psychiatric patients.
AB  - The aim was to determine the rate of dissociative disorders among psychiatric in-
      (n = 34) and out-patients (n = 37) and to compare the rate to that of nonclinical
      subjects (n = 297). Dissociative disorders (17% of patients) could be grouped
      according to the severity of the symptoms and their relation to affective
      disorders.

PMID- 14969782
TI  - Combination of amisulpride and olanzapine in treatment-resistant schizophrenic
      psychoses.
AB  - Treatment-resistant schizophrenia often leads to combined application of
      antipsychotic drugs. We report first experience with the combination of
      olanzapine and amisulpride. Improvement of psychopathological state and side
      effects could be achieved, and drug doses were lower than under monotherapy. We
      thus conclude that this approach represents a useful therapeutic option.

PMID- 14969783
TI  - Remission of positive symptomatology of a schizophrenic psychosis after
      withdrawing lamotrigine: a case report.

PMID- 14969784
TI  - Olanzapine use in a patient with schizophrenia and the risk of diabetes.

PMID- 14969785
TI  - Pericardial and bilateral pleural effusion associated with clozapine treatment.

PMID- 14969786
TI  - Modafinil as an alternative to light therapy for winter depression.

PMID- 14969790
TI  - Measuring beyond the quality of life.

PMID- 14969791
TI  - n-of-1 trials and their combination: suitable approaches for CAM research?

PMID- 14969792
TI  - HIV infection after Chinese traditional acupuncture treatment.

PMID- 14969793
TI  - Effects of homeopathic Argentum nitricum on test anxiety.

PMID- 14969795
TI  - The expression of vascular endothelial growth factor in transitional cell
      carcinoma of urinary bladder is correlated with cancer progression.
AB  - Vascular epithelial growth factor (VEGF) regulates neovascualrization in
      malignant cells. VEGF as a mitogen is thought to alter cancer cell formation and
      tumor progression. We aimed to investigative the expression of the VEGF gene to
      evaluate their clinical significance in transitional cell carcinoma (TCC) of
      urinary bladder. Tissue samples from 161 patients with TCC were examined with an
      immunohistochemical stain for the expression of the VEGF gene. The expression
      rate was compared to 32 normal bladder mucosal samples obtained from
      transurehtral surgery from noncancer patients. The results revealed significant
      differences between normal urothelium (0%) and cancer tissue (54.7%) for the
      positive staining of VEGF protein (P < 0.001). With the progression of tumor
      grade and clinical staging, the positive rate of VEGF gene expression
      significantly increased. Expression of the VEGF gene in the invasive group was
      greater than that in the noninvasive group (P < 0.001). The results revealed that
      expression of the VEGF gene is proportional to the formation and progression of
      TCC. Therefore, abnormal expression of VEGF genes can be used as a prognostic
      marker in TCC of urinary bladder.

PMID- 14969796
TI  - Impact of prior biopsy scheme on pathologic features of cancers detected on
      repeat biopsies.
AB  - The object of our study was to characterize the biopsy features of cancers
      detected in a repeat biopsy population stratified on the basis of the type of
      prior negative biopsy. We studied 218 patients with a prior negative biopsy who
      underwent a 10-core extended systematic biopsy scheme, and a subset (n = 139)
      underwent additional 6 anteriorly directed biopsies. Clinicopathologic features
      of patients with cancer on the biopsy were compared as a function of type of
      prior negative biopsy. Overall and unique cancer detection rates were calculated
      for each of the biopsy sites. Cancer detection rates tended to be higher in
      patients who had undergone a prior sextant biopsy compared to a prior extended
      biopsy scheme (39% vs. 28%). Trends towards more positive cores and greater total
      core length of cancer involvement were seen in patients who had undergone a prior
      negative sextant biopsy. Apical and laterally directed biopsies had higher
      overall and unique cancer detection rates in patients who had undergone a prior
      negative sextant biopsy. Anteriorly directed biopsies had a low unique cancer
      detection rate in all patients. We conclude that in patients undergoing repeat
      biopsy, the detection rate is affected by the extent of the prior biopsy.
      Clinicopathologic features of cancers detected on repeat biopsy tend to be worse
      in patients who have undergone a prior negative sextant biopsy compared to a
      negative prior extended biopsy.

PMID- 14969797
TI  - Analgesic therapy and the prevention of bladder cancer.
AB  - The aim of this study was to measure the association between analgesic use and
      risk of bladder cancer among patients seen at the James A. Haley Veterans'
      Administration (VA) Hospital in Tampa, FL. A total of 330 cases were obtained
      using a combination of computerized pathology records, and inpatient and
      outpatient diagnoses. Controls were randomly selected from the VA computerized
      administrative database, and 1293 controls were included for analysis.
      Unconditional logistic regression analysis was performed to assess the risk of
      bladder cancer after adjusting for age, gender, and cigarette smoking. Among
      analgesic users, we were able to identify a nearly 20% reduction in risk
      potentially consistent with a protective role (OR = 0.81, 95% CI = 0.63, 1.05).
      Nonsmokers had a 43% decrease in risk (OR = 0.57, 95% CI = 0.33, 0.98). While
      smoking is a strong and recognized cause of bladder cancer, 50% of bladder cancer
      cases are not attributable to tobacco consumption. Given that nonsmokers
      prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) were observed to have a
      43% reduction in risk, it is important to study whether nonsmokers may benefit
      from therapy with NSAIDs.

PMID- 14969798
TI  - The UroVysion fluorescence in situ hybridization assay is an effective tool for
      monitoring recurrence of bladder cancer.
AB  - The newly developed UroVysion fluorescence in situ hybridization (FISH) probe was
      applied to urine specimens from 19 patients being monitored for recurrence of
      bladder cancer. The results for the multi-target DNA FISH assay were compared
      with independent analyses of urine cytology and flexible cystoscopy. Patients
      with tumors identified through the cystoscopy exam were biopsied and/or underwent
      surgery. In 12 patients with normal cytoscopy, cytology and FISH were also
      normal. Therefore, the specificity of these two tests was 100%. In 7 patients, a
      tumor was diagnosed by cystoscopy, and 3 of them had abnormal urine cytology
      while 6 of them had an abnormal result in the FISH assay. Accordingly, the
      sensitivity was 43% for the cytology and 87% for the FISH test. Interestingly, a
      pT1G3 tumor in a bladder diverticulum was not detected by cytology or the FISH
      test. These results agreed with a large series previously published using similar
      FISH probes and support the proposal for a multicenter trial to confirm the
      usefulness of the UroVysion probe as a screening tool to select patients for
      cystoscopy.

PMID- 14969799
TI  - Postprostatectomy cancer-free survival of African Americans is similar to non
      African Americans after adjustment for baseline cancer severity.
AB  - African American men with localized prostate cancer are less likely than White
      men to receive a radical prostatectomy. This disparity may exist because African
      American men have prostate cancers that are more biologically aggressive. We
      investigated if similar stage cancers of African American men and White men show
      differences in cancer control after radical prostatectomy. Men with localized
      prostate cancer who underwent radical prostatectomy during a 6-yr period were
      stratified by race, and time to prostate-specific antigen recurrence was
      measured. We used Chi-square and t-tests to compare baseline clinical and
      pathological factors based on race. Cox proportional hazards model was used to
      determine effects of race on cancer control while controlling for baseline
      measures of cancer severity. There were 1,228 cases evaluated. At baseline,
      African American men were treated at a significantly younger age than White men
      (P = 0.0027) but showed no significant difference in prostate-specific antigen
      PSA, Gleason score, pathology stage, maximum tumor dimension, and surgical margin
      status. Multivariable Cox proportional hazards analysis controlling for cancer
      severity at prostatectomy revealed that cancer-free survival was not worse among
      African Americans compared to other subjects (P = 0.16). The responsiveness of
      prostate cancers among African American men to radical prostatectomy was similar
      to White men of similar stage and grade. Early detection in African American men
      may facilitate diagnosis of cancer amenable to prostatectomy. Studies are needed
      to evaluate the possible interaction of prostate cancer stage and grade shift in
      African American men and the disease free survival in this population.

PMID- 14969800
TI  - LINAC radiosurgery for brain metastasis of renal cell carcinoma.
AB  - The purpose of the study was to evaluate the efficacy and toxicity of
      stereotactic radiotherapy in the treatment of the brain metastasis of renal cell
      carcinoma. From 1994 to 2001, 28 patients presenting with 65 metastases of renal
      cell cancer were treated by radiosurgery. Median age was 55 years (35-75), and
      median Karnofski performance status ranges between 50 and 100. Seven patients had
      received whole brain radiotherapy (WBRT) before radiosurgery. Twelve patients
      were treated by radiosurgery for 1 metastasis, 5 patients for two metastases and
      6 for three, and 5 for more than three metastases. One procedure was performed in
      22 patients and, 2 or 3 procedures for 6 patients. Median metastasis diameter was
      19 mm (5-55 mm). Median metastasis volume was 1.28 cc (0.02-28 cc). Irradiation
      was delivered by linear accelerator. Median minimal dose (on the 70% isodose) was
      14.7 Gy (10.8 Gy, 19.5 Gy), median maximal dose (at the isocenter) 20.5 Gy (14.3
      Gy, 39.6 Gy). Median follow-up was 14 months (1-33). Two metastases progressed
      (3%), 2 and 12 months after radiosurgery. Overall, crude local control rate was
      97% and 3-, 6- and 12-month local control rates were 98% +/- 2%, 98% +/- 2%, and
      93% +/- 5%, respectively. In univariate analysis, no prognostic factor of local
      control was retrieved. Median brain disease-free survival was 25 months after RS.
      the 3-, 6- and 12-month distant brain control rates were 91% +/- 4%, 91% +/- 4%,
      and 70% +/- 12%, respectively. Median survival duration was 11 months. The 3-, 6
      , 12- and 24-month overall survival rates were 82% +/- 7%, 67% +/- 9%, 48% +/-
      10%, and 33% +/- 10%, respectively. According to univariate analysis, only site
      of metastasis was overall survival prognostic factor. Radiosurgery for brain
      metastasis of renal cell carcinoma is an effective and accurate treatment. The
      use of radiosurgery alone is an appropriate management strategy for many patients
      with brain metastasis of renal cell carcinoma. Radiosurgery is efficient even
      after development of new metastasis appearing after WBRT.

PMID- 14969801
TI  - Phase II trial of vinorelbine and estramustine in the treatment of metastatic
      hormone-resistant prostate cancer.
AB  - The purpose of this study was to investigate the efficacy and safety of
      combination chemotherapy using estramustine and vinorelbine in chemotherapy-naive
      patients with hormone-resistant prostate cancer (HRPC). The patients (n = 54)
      received oral estramustine 840 mg/day on Days 1 to 14 and IV vinorelbine 25
      mg/m(2) on Days 1 and 8 of every 3 wk cycle. The median number of cycles per
      patient was 9 (range, 1 to 27). Fifty-three patients were evaluable for toxicity
      and survival and 52 for prostate specific antigen (PSA) response. Median age was
      68 (range, 46-80). PSA sustained decrease >50% was seen in 52% of patients (95%
      CI: 38-66%). A complete response was seen in 3 and a partial response in 12 of 25
      patients with measurable disease, for an overall objective response of 60% (95%
      CI: 41-79%). Improvement in performance status was observed in 30 out of 43
      evaluable for clinical benefit response. The median duration of response was 7 mo
      and median time to progression was 6 mo. The median survival time was 15 mo. The
      most common adverse event was mild gastrointestinal toxicity. In general,
      toxicity G3-4 was low: granulocytopenia Grade 3-4 (8%), thrombocytopenia Grade 3
      (6%), and anemia Grade 3 (13%). Other Grade 3 toxicities included deep vein
      thrombosis (4%), hepatic (2%), cardiac ischemia (2%), fatigue (6%), and sensory
      neuropathy (2%). There were 2 treatment-related deaths (4%). We conclude that
      vinorelbine and estramustine as used in this trial is an efficacious and well
      tolerated therapeutic regimen in the management of HRPC.

PMID- 14969802
TI  - Permanent flank bulge is a consequence of flank incision for radical nephrectomy
      in one half of patients.
AB  - The objective of the study was to determine the incidence and predictors of post
      operative pain and flank bulging in patients undergoing nephrectomy for a renal
      tumor through a flank or thoracoabdominal incision. Only one previous
      retrospective study (1974) has directly addressed this issue in urologic
      patients. This reported a 3% incidence of flank bulging. This was at variance
      with our own experience. To determine the incidence of pain and post-operative
      flank bulge after flank or thoraco-abdominal incision, a cross sectional survey
      among in 70 patients, who had a nephrectomy for a renal tumor between 1996 and
      2000, was assessed by telephone interview. Four surgeons contributed patients to
      the study. Thirty-four of seventy (49%) patients complained of a flank bulge
      persisting more than 1 yr after surgery. Durable flank pain was experienced by
      24%. This was severe in 3% of patients. Median pain magnitude was 5/10. There was
      no difference in bulge incidence between surgeons (P = 0.49). Flank bulging
      occurred more frequently in left sided nephrectomy (P = 0.054) than right. Other
      parameters including gender, age, and tumor size had no correlation with the rate
      of either complication. In all patients who described a flank bulge, the
      deformity was durable; there were no cases of spontaneous resolution. Patients
      described a significant impact on QOL, particularly in those under 60 yrs. The
      overall rate of postoperative flank bulging is considerably higher than has been
      previously reported. This deformity affects quality of life. The observation that
      almost 50% of patients experience a flank bulge following a flank incision
      supports the shift towards laparoscopic nephrectomy, and should be incorporated
      into decision making regarding the optimal surgical approach. This may be
      particularly relevant in the choice between open partial nephrectomy and
      laparoscopic radical nephrectomy in a patient with a normal contralateral kidney.

PMID- 14969803
TI  - Pathologic characterization of prostate cancers with a very low serum prostate
      specific antigen (0-2 ng/mL) incidental to cystoprostatectomy: is PSA a useful
      indicator of clinical significance?
AB  - Cystoprostatectomy specimens removed for bladder malignancy (1988-2000) at two
      referral centers (Mayo Clinic, Rochester, MN, The University Hospital of
      Innsbruck, Innsbruck, Austria) were examined for the coincidental finding of
      prostate cancer (PCA). Centralized examination of the prostate by a single
      uropathologist was performed if at the time of surgery the patient's serum PSA
      was < or =2.0 ng/mL and there were no suspicious lesions by digital prostate
      examination. Pathologic grade, stage, morphometric volume, number of tumor foci
      and association with areas of high grade prostatic intraepithelial neoplasia
      (HGPIN) were assessed by light microscopy. DNA ploidy and cellular proliferative
      index were assessed through digital image analysis. Clinically significant
      cancers were defined as tumors with > or =0.5 cc volume, Gleason 4 or 5
      architecture, pT3, positive surgical margin, multifocality >3, nondiploid DNA
      content or proliferation index >5%. From nearly 1600 cystoprostatectomy
      specimens, 129 met the enrollment criteria. Thirty-patients (23%) within this
      group had PCA identified. Sixty percent of these tumors met the criteria for a
      clinically significant cancer. Nondiploid nuclear content was present in 17%.
      HGPIN was present in 70% and directly abutting carcinoma in 86% of prostates. The
      biologic activity of PCA appears to be independent of serum PSA. Any future
      definition of a clinically significant PCA should not be solely based upon
      histologic criteria, but needs to encompass clinical parameters (age, co
      morbidities) and a noninvasive assessment of tumor volume and biologic doubling
      time.

PMID- 14969804
TI  - The metamorphosis of a postprostatectomy patient: from curable to palliative.

PMID- 14969805
TI  - Salvage radiation for a rising PSA following radical prostatectomy.
AB  - The purpose of this study was to evaluate the efficacy and complications of
      postprostatectomy therapeutic irradiation (RT) in patients with known residual
      disease. Between 1991 and 2003, 170 patients received therapeutic irradiation for
      a rising PSA following radical prostatectomy. No patients had clinical or
      radiological evidence of metastatic disease. The median pre-RT PSA level was 1.2
      ng/mL (range, 0.2-43 ng/mL). During irradiation, the PSA level was checked weekly
      (median PSA determinations: 5, range, 2-7). A patient was considered to have a
      rise/fall of PSA if the level changed by > or = 0.2 ng/mL. There were 149
      patients who received photon irradiation (median dose, 6800 cGy) and 21 patients
      received a combination of photon and neutron irradiation to a median photon dose
      equivalent of 7800 cGy. A patient was considered to have biochemical failure if
      his PSA level postnadir was measured at >0.2 ng/mL. Complications were graded
      according to the RTOG toxicity scale. The median follow-up time was 49 months
      (range, 1-137 months). Sixty-four patients (38%) had evidence of biochemical
      failure. The 7 year overall survival was 84%. At 7 years, the actuarial
      biochemical relapse free survival (bRFS) was 44%. Of the 59 patients with a
      preradiation PSA <1 ng/mL, the 5 year bRFS was 81%. This compares with 45% for
      both the PSA 1-4 and PSA >4 ng/mL group (P = 0.00008). The 3-year bRFS rates for
      patients whose PSA levels increased, decreased, and remained the same during
      radiation were 20%, 65%, and 76%, respectively (P = 0.0005). Overall survival at
      7 years in the decreased PSA group was 88% compared to 67% for those whose PSA
      level increased (P = 0.43). Thirty-three percent and 19% of the patients
      experienced Grade 2 genitourinary (GU) and gastrointestinal (GI) complications,
      respectively. Six percent and 3% of the patients had Grade 3 GU and GI
      complications, respectively. On univariate and multivariate analysis, the factors
      significantly associated with a favorable outcome were a declining PSA during RT
      and a pre-RT PSA <1 ng/mL (P < 0.001). Radiation therapy is an effective
      treatment modality for select patients with a biochemical recurrence following
      radical prostatectomy. Patients with a low preradiation PSA level (<1.0 ng/mL)
      had a significantly better outcome, which supports the early use of therapeutic
      radiation. The observation that patients with a rising PSA level during treatment
      do poorly supports the routine practice of monitoring these levels during
      radiotherapy.

PMID- 14969806
TI  - Radiotherapy for a rising PSA following radical prostatectomy.
AB  - Controversy exists regarding the management of recurrent disease, heralded by a
      rising prostate specific antigen (PSA), in men who have undergone primary
      treatment of prostate cancer by radical prostatectomy. Although retrospective in
      nature, the use of salvage radiation therapy (RT) after prostatectomy has been
      extensively investigated and reported. Salvage RT alone is likely not optimal for
      every man presenting with recurrent disease after RP. Those with palpable
      recurrent disease or unfavorable disease characteristics are less likely to
      benefit from salvage RT alone and may respond better to a combined modality
      approach. However, early referral and proper patient selection maximizes the
      potential for durable biochemical control after salvage RT in men with rising PSA
      alone.

PMID- 14969807
TI  - PSA relapse prostate cancer: the importance of tailored therapy.
AB  - Prostate specific antigen (PSA) is an invaluable tumor marker in the detection of
      early prostate cancer as well as a predictor of recurrence after treatment of
      localized disease. Current practice entails the use of factors such as pretherapy
      grade, stage and PSA, PSA doubling time, nature of previous therapy and patient
      age and functional status for a treatment recommendation. For a PSA relapse post
      radical prostatectomy, radiation therapy to the prostatic fossa is a primary
      therapeutic consideration. With careful patient selection, about 30 to 40% of
      patients are rendered disease free using this approach. For patients with
      radiation therapy as the primary treatment for their prostate cancer, salvage
      prostatectomy can be considered, but is rarely feasible. Systemic therapy with
      hormones is standard if patients are not candidates for the above mentioned
      salvage local therapies or if they relapse after exhaustive local therapies.
      Unfortunately androgen suppressive therapy is unlikely to induce cure, or
      prolonged remissions in PSA relapse prostate cancer. The strategy of addition of
      chemotherapy or biologic therapy to androgen suppressive therapy is under active
      investigation. The goal of this therapy is to make an impact on the time to
      progression to metastatic prostate cancer and correspondingly decrease prostate
      cancer related mortality. Preliminary results of studies incorporating early
      chemotherapy in combination with androgen suppressive therapy are encouraging,
      with improvement in time to progression and overall survival. The evaluation of
      biologic agents and agents with better toxicity profiles is ongoing. This is very
      important to make therapy widely applicable and to enable prolonged
      administration especially in a disease such as prostate cancer with a relatively
      long natural history. Strategies of adjuvant and neoadjuvant therapy in locally
      advanced prostate cancer are exploring the possibility of reducing the chance of
      PSA relapse by treating micrometastatic disease. This review discusses the
      current practices in risk stratification and management of PSA relapse prostate
      cancer. It also highlights the major clinical trials and areas of active
      investigation in this field.

PMID- 14969814
TI  - Can the surgeon consistently differentiate intraoperatively benign from malignant
      lymph nodes?

PMID- 14969815
TI  - Different chromosomal imbalances in metastasized and nonmetastasized tongue
      carcinomas identified by comparative genomic hybridization.
AB  - Tumors of different metastatic behavior possibly differ in genomic constitution.
      We identified molecular cytogenetic differences between a group of metastasized
      and nonmetastasized primary tongue tumors by comparative genomic hybridization.
      Most frequent chromosome copy number changes for metastasized and nonmetastasized
      tumors were +8q (100% and 71%, respectively) and +3q (56% and 43%, respectively).
      Metastasized tumors showed significantly more chromosome copy number changes than
      nonmetastasized tumors. High copy number gains were exclusively found in
      metastasized tumors for 3q23-qter, 5p, 12p and 13q21-q22. Genomic imbalances
      occurring in metastasized tumors but not in nonmetastasized tumours were +7q21
      (44%), +14q (33%), and -15q (33%). The genetic constitution of primary tongue
      tumors that metastasize differs from tongue tumors that do not metastasize. Our
      data, although obtained from a relative small group of tumors, spotlights copy
      number gain of chromosome region 7q21 as a potential marker for metastatic
      behavior.

PMID- 14969816
TI  - The cost-effectiveness of Foscan mediated photodynamic therapy (Foscan-PDT)
      compared with extensive palliative surgery and palliative chemotherapy for
      patients with advanced head and neck cancer in the UK.
AB  - This study aimed to analyse the cost-effectiveness of Foscan mediated
      photodynamic therapy (Foscan-PDT) compared with palliative chemotherapy,
      extensive palliative surgery or 'no treatment' for patients with advanced head
      and neck cancer in the UK. A computerised cost-effectiveness model was
      constructed using published effectiveness data and unit costs for each of the
      treatment arms. Where possible, published resource use data were also used. In
      the absence of such information, expert opinion informed data input. Robust
      sensitivity analyses were performed to negate the effect of potential over or
      underestimation of the costs used for any of the interventions. The primary
      outcome was incremental cost/life year saved (cost/LYS); the secondary outcomes
      were incremental cost/overall tumour response and incremental cost/remission.
      Foscan-PDT was associated with the greatest health gains of all three
      interventions yielding 129 extra days of life compared with no treatment and
      extensive palliative surgery and 48 extra days of life compared with four cycles
      of palliative chemotherapy. The unit cost of Foscan-PDT ( pound 5741) was found
      to be lower than the unit cost for four cycles of palliative chemotherapy ( pound
      9924) and extensive palliative surgery ( pound 16912). Foscan-PDT continued to
      have a lower unit cost than palliative chemotherapy until the number of
      chemotherapy cycles was reduced to two or fewer. Reducing the number of cycles
      would be likely to reduce the health gains associated with chemotherapy. However,
      even with assumed maintenance of chemotherapy efficacy, Foscan-PDT remained cost
      effective versus two or fewer chemotherapy cycles. Compared with three or more
      cycles of palliative chemotherapy and extensive palliative surgery, Foscan-PDT
      dominated with a lower unit cost and greater health gains. Compared with giving
      no treatment, Foscan-PDT was a cost-effective treatment option at pound
      14206/LYS. Sensitivity analysis showed that Foscan-PDT remained cost-effective
      when the costs used for the comparators were decreased and/or the costs used for
      Foscan-PDT were increased. Foscan-PDT is a clinically and cost-effective
      treatment option for patients with advanced head and neck cancer compared to
      palliative chemotherapy, extensive palliative surgery or 'no treatment'.
      Furthermore, Foscan-PDT offers patients, with traditionally very limited
      treatment options, a unique chance of tumour response, remission and increased
      life expectancy.

PMID- 14969817
TI  - Overexpression of cyclooxygenase-2 is associated with radioresistance in oral
      squamous cell carcinoma.
AB  - Cyclooxygenase-2 (COX-2), an inducible isoform of cyclooxygenase, is
      overexpressed in many types of malignant tumors, which in turn may stimulate
      tumor growth and protect against damage by irradiation or cytotoxic agents. The
      purpose of this study is to investigate the relationship between the radiation
      sensitivity and elevated level of COX-2. Radiation sensitivity of the eight oral
      SCC cell lines differed greatly in their response to radiation. Further, the
      level of the COX-2 expression correlated inversely with increased tumor radiation
      sensitivity. The similar significant association between the response to
      preoperative radiation therapy and COX-2 overexpression was observed in the oral
      SCC patients. In addition, treatment with a COX-2 selective inhibitor enhanced
      the radioresponse of HSC-2 cell, which constitutively expressed COX-2. These
      results suggested that COX-2 expression level correlates to radiation tolerance
      and the COX-2 selective inhibitor may be a potent enhancer for tumor
      radioresponse in oral SCC.

PMID- 14969818
TI  - Combined treatment of cisplatin and overexpression of caspase-activated
      deoxyribonuclease (CAD) promotes apoptosis in vitro and in vivo.
AB  - Recent studies have demonstrated that a caspase-activated deoxyribonuclease (CAD)
      causes DNA degradation in nuclei after treatment of cells with caspase-3. In this
      study, we evaluated the effect of CAD overexpression on tumor cells treated with
      a chemotherapeutic agent in vitro and in vivo. In an in vitro study, we
      transfected mouse fibroblast L cells with a vector encoding mouse CAD and
      evaluated the therapeutic potential of CAD gene transfer to L cells treated with
      cisplatin (CDDP). In an in vivo study, percutaneous transfer of the mouse CAD
      gene by particle-mediated (gene gun) delivery caused overexpression of CAD in
      mouse squamous cell carcinoma (SCC). Our results showed that a combined treatment
      of CDDP and exogenous introduction of the CAD gene into tumor cells in vitro and
      in vivo arrested tumor growth and induced apoptosis. These results suggest that
      combined treatment of CDDP and exogenous CAD expression might be a useful
      strategy for cancer therapy.

PMID- 14969819
TI  - Proteomics analysis of differentially expressed metastasis-associated proteins in
      adenoid cystic carcinoma cell lines of human salivary gland.
AB  - Metastasis is the most insidious and life threatening aspect of cancers. However
      little is known about the molecular mechanisms of tumor metastasis. A poorly
      metastatic Acc-2 cell line and highly metastatic Acc-M cell line were selected as
      an experimental model to study on metastatic mechanisms and antimetastatic
      procedures. In the present study, two-dimensional gel electrophoresis and mass
      spectrometry are combined to approach the protein profiles associated with tumor
      metastasis between Acc-2 and Acc-M cell lines. Image analysis of silver stained 2
      dimensional gels revealed that 12 protein spots showed significantly quantitative
      and qualitative variations and mass spectrometry is utilized to further identify
      these spots. Of the identified proteins, transketolase, Dim1p, v-Ha-ras oncogene,
      type I collagen pro alpha, tumor necrosis factor (ligand) superfamily member 4,
      and pirin etc, have shown associations with distinct aspect of tumor metastasis
      to some extent. The dissimilar expression patterns of these 12 spots indicate the
      different roles they may play involved in tumor metastasis.

PMID- 14969820
TI  - Numerical aberrations of chromosomes 8, 9, 11, and 17 in squamous cell carcinoma
      of the pharynx and larynx: a fluorescence in situ hybridization and DNA flow
      cytometric analysis of 50 cases.
AB  - Squamous cell carcinoma of the pharynx and larynx (SCCPL) is a genetically
      complex disease and is frequently associated with nonrandom chromosomal
      alterations. Fifty primary SCC of the pharynx (oropharynx, n=11): see and
      hypopharynx, n=11) and larynx ( n=28) were examined for numerical aberrations of
      chromosomes 8, 9, 11, and 17 with a panel of chromosome-specific repetitive DNA
      probes by fluorescence in situ hybridization (FISH). DNA ploidy analysis was also
      performed by flow cytometry (FCM). Aneusomic copy numbers of chromosomes 8, 9,
      11, and 17 were discovered in 66%, 68%, 68% and 78% of tumors, respectively. FCM
      showed abnormal DNA content in 74% of cases (mean DNA index=1.69). Polysomy was
      the main finding in both DNA-aneuploid and DNA-diploid tumors (64.5% of cases).
      Numerical aberrations of chromosomes 8 and 11 correlated to DNA ploidy by FCM (P<
      0.05). Aneusomy was present in 69.23% of DNA-diploid tumors. Marked intratumoral
      and intertumoral chromosomal heterogeneity was noted between individual tumors,
      suggesting a notable heterogeneity in aneuploid and diploid cell populations.
      Interphase FISH can be used to study important cytogenetic changes which occur
      during the development of SCC of the pharynx and larynx.

PMID- 14969821
TI  - The mRNA profile of genes in betel quid chewing oral cancer patients.
AB  - Oral cancer is one of the most common types of human cancer in the world.
      Although the risk factors for oral cancer are well-recognized in different
      countries, the molecular mechanism responsible for this malignancy remains
      elusive particularly in the countries where betel quid chewing is prevalent. The
      cDNA microarray analysis was used to analyse the mRNA expression patterns of 1177
      genes in ten oral cancer patients with betel quid chewing history. Eighty-four
      genes involving cell adhesion, cell shape, growth, apoptosis, angiogenesis,
      metastasis, and metabolism were deregulated. Although the expression profile of
      these genes was shared by certain clinical patients, there was no significant
      association of the expression profile with clinical staging. Functional
      implication of four validated genes including caspase-1, STAT-1, COX-2 and
      pleiotrophin was discussed. This study provides pilot data for understanding the
      pathogenesis of oral cancer in countries like Taiwan where betel quid chewing is
      prevalent.

PMID- 14969822
TI  - Recurrent carcinoma of the head and neck: treatment strategies and survival
      analysis in a 20-year period.
AB  - Following clinical diagnosis of a recurrent tumor, curative treatment is seldom
      available. Depending on the size of the recurrent tumor and the patient's general
      health condition extensive surgical resections and reconstructions are avoided in
      favor of non-surgical palliative intended treatment modalities. According to the
      literature location of the tumor, tumor size, as well as R-1- and R-2-resection
      rates are the most frequent reasons for the development of recurrent tumors. In a
      retrospective evaluation a population of 1000 patients who were treated for a
      primary head and neck cancer during the period from 1979 to 1996 were analysed
      descriptively. Survival probabilities of patients with recurrent tumors were
      calculated according to the product-limit method by Kaplan-Meier, different
      treatment concepts were compared and analysed with the log-rank test for
      significant differences. The largest proportion of primary tumors involved the
      floor of mouth ( n = 369, 36.9%). A total of 198 patients (19.8%) developed a
      recurrent cancer; 79.8% of patients experienced a recurrent cancer within two
      years following primary treatment. Within the group of T1/T2 tumors the incidence
      of recurrent tumors was 28.9%, whereas the incidence in the T3/T4 group was
      44.6%. Tumor infiltration of the resection margins was detected in 12.9%. In line
      with the literature, tumor infiltration of the resection margins is a relevant
      prognostic factor, therefore intraoperative frozen section must be recommended.
      Treatment with curative intention, in particular extensive surgical resections,
      is seldom possible, and requires always a very intensive discussion with the
      patient.

PMID- 14969823
TI  - Trends in oral cancer mortality in Europe.
AB  - Mortality from oral cancer has been rising appreciably in most European countries
      up to the late 1980s, essentially for men. To update trends in oral cancer, death
      certification data from oral and pharyngeal cancer for 27 European countries were
      abstracted and analysed from the WHO mortality database over the period 1980-99.
      Oral cancer mortality in men has started to decline since the late 1980s in most
      western countries, although some persisting upward trends were registered for
      Belgium, Denmark, Greece, Portugal, or Scotland. Persisting rises were observed
      for most central and eastern Europe up to the mid 1990s, reaching exceedingly
      high rates in Hungary (20.2/100000 at all ages, 51.4 at age 35-64), Slovakia,
      Slovenia, and the Russian Federation. Some levelling of rates in some countries,
      such as Poland or the Czech Republic, was observed over more recent calendar
      years. Oral cancer was low, but moderately upwards in European women, mainly from
      central and eastern Europe. These trends should be essentially interpreted in
      terms of patterns and changes in exposure to alcohol and tobacco, and call for
      urgent control of these factors, as well as for improved diagnosis and management
      of oral cancer in central and eastern Europe.

PMID- 14969824
TI  - Proliferative verrucous leukoplakia: unusual locations of oral squamous cell
      carcinomas, and field cancerization as shown by the appearance of multiple OSCCs.
AB  - Proliferative verrucous leukoplakia (PVL) is an uncommon entity with a high
      tendency to develop oral squamous cell carcinomas (OSCCs). The objective of this
      study was to analyse the presence of various OSCCs in the same patient with PVL.
      We studied 19 patients with PVL who had developed at least one OSCC. We analysed
      how many of these developed more than one OSCC over a period between 24 and a
      maximum of 130 months, indicating the location of their OSCC, clinical type and
      the time lapse between the appearance of each of the different OSCCs in the same
      patient. Of the 19 patients, 10 presented more than one of these cancers, one of
      whom even went on to develop five different cancers. The most frequent location
      of OSCC was the gingiva and the palate; the least common was the tongue/floor of
      mouth. Ninety percent were women and 20% were smokers. The average time elapsed
      between the detection of the first tumour and the appearance of the second was
      19.20 months (SD 13.41). Our patients with PVL developed a high frequency of
      OSCCs, on many occasions manifesting several cancers at different oral locations,
      thus demonstrating the field cancerization of this entity. The OSCC in PVL
      patients were at sites quite uncommonly affected in patients who develop OSCC in
      the absence of PVL.

PMID- 14969825
TI  - Ameloblastic fibrosarcoma or odontogenic carcinosarcoma: a matter of
      classification?
AB  - A biphasic odontogenic tumor with aggressive clinical behaviour is reported. The
      tumor arose posterior to the right mandibular third molar involving the angle of
      the mandible and the ascending ramus. Within a 5 years period the patient
      suffered from two episodes of local progression and final disease generalization
      occurred 6 years after initial surgical therapy. On histopathologic evaluation,
      both recurrences and the distant metastasis preserved the biphasic pattern seen
      in the primary tumor with both epithelial and mesenchymal components exhibiting
      clear cytological features of malignancy. There was no evidence of sarcomatous
      overgrowth within the progression of the tumor. By contrast, the proportion of
      the epithelial component was even enlarged in the second recurrence. Thus, both
      pathologic features and clinical behaviour clearly distinguishes this tumor from
      ameloblastic fibrosarcoma and demonstrates the clear morphological as well as
      clinical characteristics of a true malignant mixed type tumor with a definite
      sarcomatous and carcinomatous component. Thus, even though a very rare lesion,
      our case supports the consideration of the odontogenic carcinosarcoma as an
      individual entity.

PMID- 14969826
TI  - Embryonal rhabdomyosarcoma of the tongue in old age.
AB  - Rhabdomyosarcoma represents the most common soft tissue sarcoma of patients under
      15 years of age, but it is definitely rare in subjects older than 45. A very rare
      case of embryonal type rhabdomyosarcoma of the tongue in a 65-year-old man is
      reported. The adult patient was treated with surgery and post-operative adjuvant
      radiotherapy and is disease-free at 48 months of follow-up. TUNEL analysis showed
      that apoptosis was present in 10% of the cells, thus suggesting that an high
      number of apoptotic cells may represent an indicator of good prognosis for this
      malignancy.

PMID- 14969827
TI  - Comment on "low prevalance of oral leukoplakia in a representative sample of the
      US population" Scheifele et al. [Oral Oncology 39 (2003) 619-625].

PMID- 14969829
TI  - Hyperlipidemia and liver diseases.

PMID- 14969830
TI  - Isolated hepatic perfusion: a regional therapy for liver cancer.
AB  - BACKGROUND: Many treatments have been proposed for non-resectable primary or
      secondary hepatic cancer but the results have been disappointing. Isolated
      hepatic perfusion (IHP) was attempted five decades ago but it has been accepted
      recently after spectacular tumour responses were obtained by several phase I-II
      trials. DATA SOURCES: An English-language literature search using MEDLINE (2003),
      Index Medicus (2003) and bibliographic reviews of books and review articles. IHP
      and its history and recent clinical application. RESULTS: IHP offers unique
      pharmacokinetic advantages for locoregional chemotherapy and biotherapy. Surgical
      isolation of the liver and percutaneous techniques using balloon occlusion
      catheters are reliable and safe. They appear to have significant efficacy even in
      patients with advanced tumor burden or those with tumors refractory to other
      types of therapy. CONCLUSION: IHP which has been developed in recent years is
      becoming a promising strategy for the treatment of unresectable liver cancer.

PMID- 14969831
TI  - Pathogenesis and treatment of hepatitis C virus-related liver diseases.
AB  - BACKGROUND: Few comprehensive reviews on the pathogenesis of hepatitis C virus
      (HCV)-related liver diseases have been presented to the present. This article was
      to review the pathogenesis and treatment of HCV-related liver diseases. DATA
      SOURCES: Data presented here are mostly taken from Japanese studies. RESULTS: HCV
      infection is characterized by persistent inflammation of the liver and frequent
      development of hepatocellular carcinoma (HCC) in most cases. These characteristic
      evidences could be explained by immunological alterations and oxidative stress in
      the hepatocyte caused by HCV infection. Interferon (IFN) treatment is carried
      out, at present, not only for the elimination of infected HCV for the treatment
      of chronic liver diseases, but also for both the prevention of HCC and the
      treatment of advanced HCC with chemotherapy. The treatment for oxidative stress
      is also important for non-responders to IFN. CONCLUSION: It is important to
      understand the pathogenesis of HCV-related liver diseases for a successful
      treatment.

PMID- 14969832
TI  - Prevention and treatment of hepatic artery thrombosis after liver
      transplantation.
AB  - BACKGROUND: Hepatic artery thrombosis (HAT) which is a serious complication after
      orthotopic liver transplantation (OLT) remains a significant cause of graft loss.
      The purpose of this study was to sum up our experiences in the prevention,
      diagnosis and management of HAT after liver transplantation. METHODS: From April
      1993 to September 2003, a total of 198 patients underwent OLT at our hospital.
      The hepatic artery was anastomosed using 7/0 prolane with running continuous
      suture in 96 patients (group 1) and with interrupted suture in 102 (group 2).
      Ultrasonography was performed every day in two weeks after operation and
      selectively afterwards. RESULTS: HAT occurred in 6 patients (6.3%, 6/96) of group
      1, and in 1 (1%, 1/102) of group 2 (X2=4.027, P=0.045). Six patients received
      emergency thrombectomy, and 1 conservative therapy but died from tumor recurrence
      eventually. Biliary complication developed in 3 patients after thrombectomy of
      whom 2 died of liver failure and one waited for retransplantation. In the other 3
      patients after thrombectomy, 1 died of renal failure, and 2 survived. The
      mortality of patients with HAT was 57.1% (4/7). CONCLUSIONS: The technique of
      hepatic arterial anastomosis is the key factor for the prevention of HAT. Routine
      ultrasonography is very important in early detection of HAT after OLT. Biliary
      complication is a severe outcome secondary to HAT.

PMID- 14969833
TI  - Lamivudine prophylaxis of liver allograft HBV reinfection in HBV related
      cirrhotic patients after liver transplantation.
AB  - BACKGROUND: Liver allograft hepatitis B virus (HBV) reinfection and hepatitis B
      (HB) recurrence jeopardize the long-term survival of recipient and liver
      allograft. Lamivudine has been referred as a novel antiviral agent against HBV in
      HBV cirrhotic patients even in liver transplantation setting. We assessed the
      prophylatic effect of lamivudine on liver allograft HBV reinfection and clarified
      the dynamic changes of HBV markers in HBV related decompensated liver cirrhosis
      after liver transplantation. METHODS: Twenty-five recipients were divided into
      three groups: HBV active replication group (15 recipients), HBV inactive
      replication group (7), and control group (3). 100 mg/d lamivudine was
      administered preoperatively except in the control group. The HBV markers of
      serial sera and liver biopsy samples of the 25 recipients were evaluated
      regularly with enzyme-linked radioimmunoassay, HBV DNA fluorescent quantitative
      assay, immunohistochemical staining, labelled streptavidin biotin (LSAB) and
      digoxin labelled HBV DNA hybridization in situ. The dynamic alternation of HBV
      markers under lamivudine prophylaxis was observed. RESULTS: In the HBV active
      replication group who had received lamivudine 2 weeks before liver
      transplantation, serum HBV DNA positive converted to negative by 80%. HBsAg of
      all recipients disappeared after liver transplantation, but corresponding
      antibodies of HBV appeared within one week after the operation. HBsAb 9/15, HBcAb
      13/15 and HBeAb 11/15 appeared and subsided gradually within 24 weeks. HBV DNA in
      sera was kept negative; HBsAg, HBcAg and HBV DNA hybridization in situ of liver
      biopsy samples remained negative after use of lamivudine. Ten of the 15
      recipients showed clearance of HBV, and per se HBV markers were undetectable both
      in serum and liver biopsy samples between 12 to 44 weeks (24 weeks on average).
      The 1-, 2-year survival rates were 83% in this group. Two of the 15 recipients
      developed HBV allograft reinfection or recurrence of hepatitis 2 years after
      lamivudine monoprophylaxis (2/15, 13.3%). In the HBV inactive replication group,
      the outcome was similar to that of the HBV active group. The HBV antibody
      frequency was HBsAb 4/7, HBcAb 6/7, and HBeAb 2/7. Three of 7 recipients showed
      HBV clearance both in sera and liver biopsy samples, whereas in the control group
      all 3 recipients developed HBV allograft reinfection and recurrent hepatitis 8,
      10, 12 months postoperatively; one of them died of fibrosing cholestatic
      hepatitis, and the remaining 2 recovered after additional lamivudine therapy. The
      overall allograft reinfection rate was 9.1% (2/22) and the overall 1-, 2-year
      survival rates were 87% in the lamivudine prophylaxis group. CONCLUSIONS:
      Lamivudine prophylaxis can prevent effectively liver allograft from HBV
      reinfection in patients with HBV-related decompensated liver cirrhosis even in
      HBV active replication recipient after liver transplantation. Its long-term
      outcome remains to be studied.

PMID- 14969834
TI  - Improved two-cuff technique for orthotopic liver transplantation in rat.
AB  - BACKGROUND: The first orthotopic liver transplantation in rat (ROLT) was reported
      by Lee in 1973. Kamada innovatively applied cuff technique to ROLT in 1979.
      However, the operative procedures were highly demanding and the operative
      mortality was relatively high. The purpose of this study was to improve the model
      of ROLT, simplify operative procedures, and enhance the successful rate of
      operation. METHODS: Orthotopic liver transplantation was performed in 160 Wistar
      rats by improved two-cuff technique. The portal vein between donor and recipient
      was anastomosed with the cuff technique. The same method was used to anastomose
      the infrahepatic vena cava. The suprahepatic vena cava and the hepatic artery
      were anastomosed by microvascular suturing and the bile duct was anastomosed end
      to end by a Teflon catheter. RESULTS: The average time for donor operation, graft
      preparation and anhepatic phase was 31 minutes, 14 minutes and 13 minutes,
      respectively. The anastomosis time for the suprahepatic vena cava, portal vein,
      infrahepatic vena cava, hepatic artery and bile duct was 7 minutes, 2 minutes, 2
      minutes, 8 minutes and 1 minute, respectively. The main causes for operative
      mortality were pneumothorax, anesthesia, air embolism and massive bleeding, and
      the successful rate of operation was 92.5%. The causes for death after operation
      were stoma bleeding, infection, biliary obstruction and graft failure.
      CONCLUSION: The improved two-cuff technique can reduce operative mortality,
      enhance survival rate, and serve as an ideal method for the establishment of
      animal model of ROLT.

PMID- 14969835
TI  - Plasma levels of tumor necrotic factor-alpha and interleukin-6, -8 during
      orthotopic liver transplantation and their relations to postoperative pulmonary
      complications.
AB  - BACKGROUND: Pulmonary complications after orthotopic liver transplantation (OLT)
      include high morbidity and mortality. Experimental data have suggested hepatic
      ischemia and reperfusion are induced by pro-inflammatory cytokines. The high
      level of inflammatory cytokines might additionally influence pulmonary capillary
      fluid filtration. The objectives of this study were to measure the concentrations
      of tumor necrotic factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin
      8 (IL-8) during OLT and to investigate the relationship between these cytokines
      and postoperative pulmonary complications. METHODS: Twenty-two patients
      undergoing OLT were divided into two groups according to whether they had
      postoperative pulmonary complications: group A consisting of 8 patients with
      postoperative pulmonary complications, and group B consisting of 14 patients
      without postoperative pulmonary complications. Enzyme-linked immunoassay (ELISA)
      was used to determine serum TNF-alpha, IL-6 and IL-8. Blood samples were taken at
      the beginning of operation (T0), clamping and cross-clamping of the inferior cava
      and portal vein (T1, T2), 90 minutes and 3 hours after reperfusion (T3, T4) and
      24 hours after operation (T5). RESULTS: The level of PaO2/FiO2 in group A was
      lower than that in group B (P<0.05). The concentrations of TNF-alpha, IL-6 and IL
      8 in the two groups increased rapidly at T2, peaked at T3, decreased rapidly
      after T3 until 24 hours after operation. The concentrations of TNF-alpha, IL-6
      and IL-8 in group A were higher than those in group B at T2, T3, and T4 (P<0.05).
      CONCLUSION: After un-clamping of the inferior cava and portal vein, the serum
      concentrations of TNF-alpha, IL-6 and IL-8 increased may be related to pulmonary
      injury after hepatic ischemic reperfusion.

PMID- 14969836
TI  - A randomized trial of a 4- vs 12-week daily interferon dose regimen combined with
      ribavirin in treatment of patients with chronic hepatitis C.
AB  - BACKGROUND: Standard combination-therapy of ribavirin with alternate day
      interferon (IFN) in patients with chronic hepatitis C (CHC) has been reported to
      achieve 30%-55% sustained viral response. Early reduction of viral load by daily
      dosage of IFN could enhance viral clearance. However, the duration of daily
      dosage protocol and the likely side-effects have not been well studied. We
      compared the efficacy and safety of a 4- vs 12-week daily IFN dosage in patients
      with CHC. METHODS: Fifty-nine, histologically proven CHC patients having ALT
      levels >1.5 x ULN were divided randomly into 2 groups, group I was given IFN 3
      MIU daily for 4 weeks, followed by tiw up to 12 months and group II was given IFN
      3 MIU daily for 12 weeks, followed by tiw up to 12 months. Ribavirin was given in
      a dose of 800-1200 mg/d for 12 months. RESULTS: Fifty-two of the 59 patients
      (group I=28; group II=24) completed the study. The pretreatment variables and the
      prevalence of HCV genotype 1 were comparable between the groups. Nine patients
      (29%) in group I and 6 (25%) in group II had stage 3, 4 fibrosis. At the end of
      4, 12, 24 and 52 weeks, HCV RNA negativity was observed in 27%, 54%, 65% and 71%
      in group I and 38%, 54%, 71% and 75% in group II, respectively (P=ns). Four of
      the eight (50%) patients with genotype 1 and 30 (69.8%) of 43 patients with
      genotype non-1 responded to therapy (P=ns). Sustained viral response was achieved
      in 61% and 71% in groups I and II, respectively. None of the variables predicted
      non-response precisely. No serious adverse effects were observed and they were
      comparable between the two groups. CONCLUSION: Daily IFN dosage with ribavirin is
      safe and can achieve response in up to 65% patients. Since the efficacy of a 4
      week daily dosage of IFN is comparable to a 12-week schedule, we recommend the
      former regimen.

PMID- 14969837
TI  - Percutaneous intratumoral injection of traditional Chinese herbal compound
      medicine Star-99 in treatment of hepatocellular carcinoma of mice.
AB  - BACKGROUND: Unresectable hepatocellular carcinoma (HCC) lacks effective therapy
      and entails very poor progress. In 1991, we found that Chinese herbal compound
      Star-99 has potentially effect on HCC. The purpose of this study was to probe the
      anti-cancer effect and the mechanism of focal injection of Chinese herbal
      compound Star-99 into HCC of mice. METHODS: In 32 nude mice transplanted with
      human hepatocellular carcinoma SMMC-7721, 16 received hypodermic implant and the
      other 16 orthotopic liver transplant. They were randomly divided into three
      groups: Star-99 group (Chinese herbal compound, 16 mice), alcohol group (8) and
      saline group (8), respectively. Intratumoral injection of Star-99, alcohol and
      saline was carried out 10 days after transplantation of HCC. Twenty days after
      the first injection, the nude mice were killed after being injected every 5 days
      with a total of 4 injections in each mouse. Tumor tissues were examined
      pathologically or via an electron microscope and flow cytometrical (FCM) DNA
      analysis. The three diameters of the tumor were measured with high-frequency
      ultrasound before and after injection, and the growth index was calculated with
      the following formula: volume of tumor (after treatment-before treatment)/volume
      of tumor (before treatment). Double-blind method was applied in the experiment.
      RESULTS: The growth index of the Star-99 group (0.068+/-0.022) and the alcohol
      group (0.079+/-0.024) was markedly lower than that of the saline group (4.345+/
      1.453, P<0.01), but there was no significant difference between the Star-99 and
      alcohol groups. Coagulation (8/8) was the major pathological change in the
      alcohol group. In the Star-99 group, however, the phenomenon of lymphocytes
      attacking cancer cells could even be seen under the electron microscope. The
      typical apoptosis cells and apoptosis bodies as well as the collagen fibrae lined
      in mass could also be seen in the group (14/16). FCM DNA analysis showed that the
      rate of apoptosis in the Star-99 group (93.8%) was significantly higher than that
      in the alcohol (12.5%) and saline groups (12.5%) (P<0.01). CONCLUSIONS: This
      study shows that Star-99 markedly inhibits and destructs hepatocellular cancer
      cells. Star-99 is effective to directly destroy the membrane, cytoplasm and
      nuclei of tumor cells, causing their crumbling, activate the immune function and
      inflammatory reaction of nude mice, and induce the apoptosis of cancer cells. The
      effect of Star99 is significantly different from that of alcohol that mainly
      causes coagulation of cancer cells. Star-99 is feasible in the treatment of HCC.

PMID- 14969838
TI  - Therapeutic effect of transcatheter arterial chemoembolization and percutaneous
      injection of acetic acids on primary liver cancer.
AB  - BACKGROUND: The resection rate of primary liver tumor in China is only about 20%.
      A lot of patients with moderate and advanced liver tumor may lose the chance of
      operation. The objective of present research was to study the efficacy of
      transcatheter arterial chemoembolization (TACE) combined with percutaneous
      injection of chemical agents and acetic acids in the treatment of patients with
      primary liver cancer (PLC). METHODS: Thirty-three patients with middle and
      advanced stage of PLC were divided into two groups: percutaneous injection of
      chemical agents and acetic acids (15 patients, group A) and TACE (18 patients,
      group B). RESULTS: Tumor diameter and serum AFP level reduced to 86.6% and 83.3%
      in group A, and 55.5% and 40% in group B, respectively. There was significant
      difference between the two groups (P<0.01). The 1, 2, 3, 4-year survival rates of
      group A were 96.7%, 86.6%, 51.3%, 33.3%, respectively and in group B were 66.7%,
      44.4%, 16.7%, 0%, respectively (P<0.01). CONCLUSION: TACE combined with
      percutaneous injection of chemical agents and acetic acids is efficacious to
      increase the survival rate of patients with PLC.

PMID- 14969839
TI  - Changes of plasma D(-)-lactate, diamine oxidase and endotoxin in patients with
      liver cirrhosis.
AB  - BACKGROUND: Plasma D(-)-lactate and diamine oxidase (DAO) can reflect patients'
      intestinal mucosal condition. We evaluated the changes of plasma D(-)-lactate,
      DAO and endotoxin activities and their significance in patients with liver
      cirrhosis. METHODS: Fifty liver cirrhosis patients were enrolled into
      experimental group and 30 healthy people into control group. The plasma levels of
      D(-)-lactate, DAO and endotoxin were detected spectrophotographically. RESULTS:
      The level of D(-)-lactate was significantly higher in the experimental group than
      that in the control group (P<0.01). Significant differences of D(-)-lactate
      levels were observed in Child-Pugh subgroups of the experimental group (P<0.01).
      The level of DAO was significantly higher in the experimental group than that in
      the control group (P<0.01), but the level of DAO in Child-Pugh subgroup C was
      significantly lower than that in Child-Pugh subgroup B (P<0.01). The level of
      endotoxin was significantly increased in the experimental group except Child-Pugh
      subgroup A (P<0.01). The plasma levels of D(-)-lactate, DAO and endotoxin were
      positively correlated with each other (P<0.01). CONCLUSIONS: The data suggest
      that both plasma D(-)-lactate and DAO activity are sensitive markers for early
      diagnosis of gut failure and endotoxemia in patients with liver cirrhosis. The
      impairment of intestinal barrier function may be one of the critical reasons for
      deterioration of liver cirrhosis.

PMID- 14969840
TI  - Dual fluorescence in situ hybridization in detection of HER-2 oncogene
      amplification in primary hepatocellular carcinoma.
AB  - BACKGROUND: Molecular cytogenetics of oncogene HER-2 amplification in primary
      hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to
      investigate the frequency of HER-2 oncogene amplification in primary HCC and its
      relations to clinicopathological parameters and prognosis. METHODS: Forty-two
      surgical samples from patients with primary HCC were detected for their HER-2
      oncogene amplification. The number of chromosome 17 and their ratio were tested
      by dual fluorescence in situ hybridization (FISH) technique, and then the
      correlations between HER-2 amplification, clinicopathological characteristics and
      prognosis were analyzed statistically. RESULTS: HER-2 oncogene amplification was
      detected in 9 (21.4%) of the 42 primary HCCs, including 4 patients with high copy
      (HC) (9.5%) and 5 patients with low copy (LC) (11.9%). HER-2 amplification was
      associated significantly with tumor size and postoperative survival time of HCC
      patients (P<0.05), and the presence of HER-2 gene amplification was correlated
      with postoperative relapse (P=0.257), but not related to sex, age, AFP level, HBV
      infection, histopathological grading and clinical staging of HCC patients
      (P>0.05). The HER-2 oncogene copy was examined in 31 (73.8%) of the 42 primary
      HCCs, consisting of 9 patients with HER-2 amplification (21.4%) and 22 patients
      with aneuploidy (52.4%). No significant relations were observed between the HER-2
      oncogene copy, patient sex, tumor size, histopathological grading, clinical
      staging, postoperative relapse and survival time (P>0.05); but the HER-2 oncogene
      copy was correlated significantly to age, AFP level and HBV infection (P<0.05).
      CONCLUSIONS: There are a lower frequency of HER-2 oncogene amplification and a
      higher frequency of chromosome 17 aneuploidy in primary HCC. HER-2 oncogene
      amplification may be involved in the development and progression of large HCC in
      some patients, and seems to be a valuably independent prognostic factor
      predicting the recurrence and poor survival in patients with large HCC.

PMID- 14969841
TI  - Efficacy of intramuscular matrine in the treatment of chronic hepatitis B.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection, a global public health problem, is
      the leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide.
      There are more than 350 million HBV carriers in the world and up to one million
      die annually due to hepatitis B associated liver disease. So far no optimal
      treatment is available for patients with chronic hepatitis B. In the paper we
      investigated the efficacy of intramuscular matrine in the treatment of chronic
      hepatitis B. METHODS: One hundred and twenty patients with chronic hepatitis B
      were randomly divided into matrine treatment group (n=60) and control group
      (n=60). The patients of the matrine group were given intramuscularly with matrine
      (an alkaloid extracted from a traditional Chinese herb Radix Sophorae
      Flavescentis by Guangzhou Ming Xing Pharmaceutical Factory, Guangzhou, China) of
      100 mg daily for 90 days in addition to conventional liver-protective drugs
      including glucurone, inosine, compound vitamin B and caryophyllin. The control
      group received conventional liver-protective drugs alone. Clinical manifestations
      and laboratory parameters including liver biochemistry and serum hepatitis B
      virus markers were monitored before and after treatment in the two groups.
      RESULTS: Significant differences were seen between the two groups in terms of
      improvement of clinical symptoms and signs, recovery of liver functions, and
      serum conversion from hepatitis Be antigen to HBe antibody and from positive to
      negative serum HBV DNA (P<0.05-0.01). The result of the matrine group was more
      marked than that of the control group. Serious side-effects were not observed
      except mild pain at the site of injection of matrine in a few patients.
      CONCLUSION: These results indicate that intramuscular matrine may be an
      economical, efficacious, safe drug for the treatment of chronic hepatitis B.

PMID- 14969842
TI  - Treatment of membranous Budd-Chiari syndrome: analysis of 480 cases.
AB  - BACKGROUND: Budd-Chiari syndrome (BCS) presents a kind of disease resulted from
      the occlusion of hepatic vein and/or the intrahepatic inferior vena cava. Its
      different pathological types were proposed. According to our experience, the
      membranous type takes a large part of it, and we tried to explore the best
      treatment of membranous BCS through the analysis of 480 cases retrospectively.
      METHOD: The operative results of 480 patients with membranous BCS were analysed
      retrospectively. RESULTS: Patients after Kimura's finger rupture, interventional
      treatment and membrane resection were followed up with rates of 84.62%, 86.55%,
      and 87.37%, respectively. The effective rates of the three methods were 61.4%,
      91.7%, and 90.4%, respectively, and the recurrence rates of the disease after the
      3 procedures were 38.6%, 8.3% and 9.6%, respectively. The long-term effects of
      interventional treatment and resection were significantly better than those of
      Kimura's finger rupture (P<0.05). CONCLUSION: Balloon dilatation is the choice
      for membranous BCS. Patients with extensive lesion, thick membrane or recurrence
      after percutaneous transhepatic angiography should undergo membrane resection.

PMID- 14969843
TI  - Generation of high affinity human single-chain antibody against PreS1 of
      hepatitis B virus from immune phage-display antibody library.
AB  - BACKGROUND: A single-chain antibody (ScFv) phage display library was created by
      cloning antigen-binding regions of V(H) (variable domain) and V(L) gene
      repertoires as fusion proteins with a minor coat protein of filamentous phage,
      from which high affinity completely humanized ScFv against PreS1 of hepatitis B
      virus could be screened and characterized. METHODS: A combinatorial library of
      phage-display human ScFv genes, which were derived from peripheral blood
      lymphocytes immunized by peptide PreS1 in vitro, was constructed. The library
      contained 7 x 10(8) clones. RESULTS: After 3 rounds panning, a high affinity
      (K=10(-7)-10(-8)mol/L) ScFv specific to PreS1 was obtained. Sequence analysis
      showed that the V(H) belonged to the V(H)4 family and V(lambda) to V(lambda)4.
      CONCLUSIONS: The described ScFv may provide a more satisfactory therapy. This
      application further illustrates that the method of in vitro antigen stimulation
      is expeditious for the source of human immune antibody library.

PMID- 14969844
TI  - Hepatic volumetry with PhotoShop in personal computer.
AB  - BACKGROUND: Convenient way to clarify liver volume or tumor volume in the liver
      is eagerly demanded by hepatobiliary surgeons, for so many aspects of clinical
      work need to know the liver volumetry. At present, some methods have been used to
      measure the liver volumetry, such as computed tomography (CT) scans, three
      dimensional ultrasound volumetric system([1]) and 3-dimensional sonography([2,3])
      et al. But enough volumetric information was failed to obtain by surgeons and a
      new way of measuring the liver volumetry that can be operated by themselves is
      exigent. Whereas we devise a new method of using PhotoShop in personal computer
      to measure the liver volumetry. METHODS: A piece of whole CT film was transformed
      to a high quality digitized image by digital camera or scanner and then the
      digitized image was conducted as JPEG file into personal computer. The JPEG image
      file of CT film was opened by PhotoShop. Determining the edge of interested
      areas, and the data of pixel values of the interested areas divided by 1 cm2
      pixel value will produce the actual area with the unit of square centimeter. If
      section thickness of CT scan is 1 cm, the sum of the areas of the liver or tumor
      in all sections naturally is the volume of the liver or tumor. RESULTS:
      Comparison of 10 hepatic volumes gained by this method and those gained by the GE
      Prospeed CT set showed a good relativity between the two groups. The volumes of
      three right lobes were calculated by this method before lobectomy and their real
      volumes were obtained postoperatively by a volumenometer. Their variation was
      limited to 5%. CONCLUSIONS: Hepatic volume obtained by PhotoShop is reliable.
      This method can be used to measure hepatic volume perfectly to meet clinical
      demand, and many parameters such as liver resection rate, graft volume can be
      achieved. The disadvantage of this method is the step of copying the pixel value
      from PhotoShop to Microsoft Excel.

PMID- 14969845
TI  - The relationship between point mutation and abnormal expression of c-fms oncogene
      in hepatocellular carcinoma.
AB  - BACKGROUND: Recent research found abnormal expression of the c-fms oncogene,
      which encodes the macrophage colony-stimulating factor receptor (CSF-1R), in
      several human carcinomas including hepatocellular carcinoma (HCC). But the
      relationship between the point mutation and abnormal expressing of c-fms oncogene
      in HCC was not clear. This study is to investigate the relationship between point
      mutation and abnormal expression of c-fms oncogene in hepatocellular carcinoma
      (HCC) and to clarify the mechanism of HCC. METHODS: The expression of c-fms
      oncogene at different levels of cell, protein and transcription was observed
      using immune histological ABC, Western blot and Northern blot. PCR-single strand
      conformation polymorphism and gene sequencing were used to detect the mutation of
      c-fms in HCC tissues and their surrounding tissues of 30 patients. RESULTS: The
      expression of c-fms was significantly higher in HCC tissues than in their
      surrounding tissues (P<0.01). Point mutation of Leu (TTG)-->Ser (TCG) at codon
      301 of c-fms amino acids was observed in 21.4% (3/14) HCC tissues. No mutation of
      c-fms oncogene was detected in the surrounding cancerous tissues. CONCLUSION:
      Point mutation at codon 301 of c-fms oncogene is one of the mechanisms of
      abnormal over-expression in HCC.

PMID- 14969846
TI  - Fine needle aspiration cytology in the diagnosis of liver lesions.
AB  - BACKGROUND: Fine needle aspiration cytology (FNAC) is a less invasive,
      inexpensive and rapid method for pathologic evaluation of hepatic masses. This
      study was to investigate the role of fine needle aspiration cytology in the early
      diagnosis of liver disease. METHODS: Fourty-six patients received fine needle (1
      mm diameter or 18G) aspiration for the diagnosis of liver disease under
      ultrasonography or computed tomography guidance. The diagnosis was verified by
      using hematoxylin and eosin (HE) staining and immunohistochemistry. RESULTS: Of
      the 46 patients, 19 had hepatocellular carcinoma (HCC), 2 cholangiocarcinoma, 1
      lymphoma, 1 carcinoid tumor, 1 squamous cell carcinoma, 1 tuberculosis, 14 no
      abnormality, and 6 red blood cells. Cytological diagnosis of 3 patients was
      inconsistent with histological diagnosis after surgery: incorrect diagnosis (2),
      and false-negative for failure of aspiration (1). CONCLUSIONS: Cytological
      diagnosis should mostly depend on cellular morphology. In addition,
      immunohistochemistry and special staining are helpful for diagnosis if cytologic
      preparation is available. Fine needle aspiration cytology of the liver is a
      diagnostic method that can be used to identify the vast majority of neoplasms of
      primary or metastatic nature.

PMID- 14969847
TI  - Effect of Maotai liquor on the liver: an experimental study.
AB  - BACKGROUND: Epidemiology investigation showed that no worker drunk Maotai liquor
      for nearly 30 years died of hepatic diseases, and no obvious hepatic fibrosis and
      cirrhosis were found in 99 workers who had drunk Maotai liquor for a long period
      by epidemiology investigation and needle biopsy. The same finding was detected in
      rats that were drunk by Maotai liquor continued for 56 days. This study was to
      investigate the effects of Maotai liquor on the liver and its mechanism of
      preventing hepatic fibrosis. METHODS: After ingestion of Maotai for 56
      consecutive days, male SD rats were killed for detecting the levels of
      metallothionein and malondialdehyde (MDA) in liver tissues. Rat hepatic stellate
      cells (HSCs) and human HSCs were cultured in vitro to observe the effect of
      Maotai on HSCs proliferation and collagen synthesis. After ingestion of Maotai
      for 14 consecutive weeks, the livers of male SD rats were harvested for
      pathohistological examination. RESULTS: The level of metallothionein in the liver
      of Maotai-induced rats increased by 22 folds, whereas the levels of hepatic lipid
      peroxide and MDA was decreased significantly (P<0.05) in Maotai-induced animals
      suffering from CCl4. Maotai demonstrated obvious inhibitory effect on
      proliferation of HSCs and the inhibition was concentration-dependent. Gene
      expression and protein secretion of collagens could also be inhibited by Maotai.
      In alcoholic group, typical liver cirrhosis was observed. In Maotai group,
      however, though fatty degeneration of hepatocytes and mild fibrosis of the
      interstitium were observed, no obvious hepatic fibrosis and cirrhosis were found.
      CONCLUSION: It might be an important mechanism of interfering the progress of
      hepatic fibrosis that Maotai increases the level of metallothionein in the liver
      and inhibits the activation of HSCs and the synthesis of collagen proteins.

PMID- 14969848
TI  - Dynamical influence of Cordyceps sinensis on the activity of hepatic insulinase
      of experimental liver cirrhosis.
AB  - BACKGROUND: Cordeceps sinensis (CS) is a herb which can inhibit the liver
      fibrosis. Hyperinsulinemia is common in liver cirrhosis patients. The activity of
      insulin degrading enzyme could reflect the metabolism of insulin. This study was
      to detect the dynamical effects and mechanisms of CS on the activity of hepatic
      insulinase in CCl4 induced liver cirrhosis in rats. METHODS: Rats were randomly
      allocated into three groups: normal group, model group and CS group. The rats in
      the normal group were sacrificed at the beginning of experiment, and the other
      two groups were sacrificed randomly at the end of the third, sixth and ninth
      weeks. Blood and tissue specimens were taken. Biochemical assays were used to
      determine the changes of alanine transaminase (ALT), albumin levels in serum. And
      radioimmunological assays were used to determine the changes of hyaluronic acid
      (HA), insulin levels in serum and the activity of hepatic insulinase. RESULTS: No
      significant differences were seen in the serum levels of ALT, albumin, HA between
      the CS group and the model group at the third and sixth weeks (P>0.05). The serum
      levels of ALT, HA in the CS group were lower than those in the model group at the
      ninth week (P<0.05), but the serum level of albumin in the CS group was higher
      than that in the model group at the ninth week (P<0.05). No significant
      differences were observed in the serum levels of insulin and the activity of
      hepatic insulinase between the CS and model groups at the third week and the
      normal group (P>0.05). The serum levels of insulin in the CS and model groups at
      the sixth and ninth weeks were higher than those in the normal group (P<0.05).
      But the activity of hepatic insulinase was lower than that in the normal group
      (P<0.05 or P<0.01). No significant differences were found in the serum levels of
      insulin and the activity of hepatic insulinase between the CS and model groups at
      the third, sixth and ninth weeks (P>0.05). CONCLUSIONS: CS may decrease the
      damage to hepatocyte by CCl4, and inhibit hepatic fibrogenesis. Six weeks after
      CCl4 administration, the activity of hepatic insulinase began decreasing. CS
      could not inhibit the decrease of the activity of hepatic insulinase.

PMID- 14969849
TI  - Effect of salvianolic acid B on Smad3 expression in hepatic stellate cells.
AB  - BACKGROUND: Salvianolic acid B (SA-B), one of water soluble compounds derived
      from Radix salviae miltiorrhizae, had good action against liver fibrosis of
      patients with chronic hepatitis. Hepatic stellate cells (HSCs) is the cellular
      resource for liver fibrogenesis, while transforming growth factor-beta1 (TGF
      beta1) is most potent fibrogenic factor. In this study we investigated the
      mechanism of SA-B action against liver fibrosis relating to the interference with
      TGF-beta1 signaling at HSC. METHODS: Hepatic stellate cells (HSCs) were isolated,
      cultured, and incubated with SA-B. The TGF-beta1 content in the supernatant of
      subcultured HSCs was assayed with ELISA. Type I collagen and Smad3 protein in TGF
      beta1-stimulated primarily cultured HSCs for 4 days were detected by Western
      blot. RESULTS: TGF-beta1 secreted in activated HSCs was more than in primary
      HSCs, and SA-B significantly decreased TGF-beta1 secretion in activated HSCs. TGF
      beta1 increased the expression of type I collagen and Smad3 protein in d4 primary
      HSCs, while SA-B inhibited their expression. CONCLUSIONS: SA-B inhibits TGF-beta1
      secretion in activated HSCs and counteracts the expression of TGF-beta1
      stimulated type I collagen and Smad3. These actions are associated with the
      effect of SA-B on liver fibrosis.

PMID- 14969850
TI  - Effects of taurine on proliferation and apoptosis of hepatic stellate cells in
      vitro.
AB  - BACKGROUND: Hepatic fibrosis, a common response to chronic liver injury, is
      characterized by increased production of extracellular matrix components, whose
      major part is produced by hepatic stellate cells (HSCs). Taurine is a sulfur
      containing beta-amino acid rich in human body, and our previous experiments
      showed that it can inhibit the deposition of the extracellular matrix in the
      damaged liver. This work was to investigate the effects of taurine on
      proliferation and apoptosis of HSC and its possible mechanism. METHODS: Cell
      proliferation was detected by the thiazole blue (MTT) colorimetric assay. Cell
      apoptosis and cell cycle were assessed via flow cytometry. The morphology of
      apoptotic cells was observed by phase-contrast fluorescent micrography after
      orange acridine staining, and the cAMP content was measured by radioimmunoassay.
      The expression of c-jun and c-fos was determined by the combination of
      immunocytochemistry and image analysis software. RESULTS: Taurine dose
      dependently inhibited the proliferation of HSCs at the concentration of 5-50
      mmol/L, resulting in more cells in the G0/G1 phase and fewer in the S phase.
      Taurine markedly increased the synthesis of cAMP and suppressed the gene
      expression of c-jun and c-fos (P<0.01) in addition to the inhibition of the
      proliferative effect of platelet-derived growth factor BB on HSC. However,
      taurine had no effect on induction of cell apoptosis. CONCLUSIONS: Taurine can
      significantly inhibit the proliferation of HSC, causing a G0/G1-phase arrest.
      This effect on HSC proliferation is associated with the enhancement of the
      synthesis of cAMP and inhibition of the gene expression of c-jun and c-fos.
      However it can not induce the apoptosis of HSC.

PMID- 14969851
TI  - Aberration of X chromosome in liver neoplasm detected by fluorescence in situ
      hybridization.
AB  - BACKGROUND: A diverse range of cytogenetic alterations of autosomal chromosomes
      has been reported to date. However, few studies have addressed the abnormalities
      of X chromosome in hepatocellular carcinoma (HCC) except sporadic reports on the
      deletion of band F1 in X chromosome, and the clonal analysis of methylation
      pattern of the X chromosome-linked human androgen receptor gene. Identification
      of specific X chromosome alterations during the course of neoplastic development
      would be essential to defining the genetic basis of HCC. Therefore, we studied
      the regularity of aberration of X chromosome in liver cancer. METHODS:
      Hepatocarcinoma cellular lines and tumor tissues were detected respectively
      through DNA probes of X chromosome after fluorescence in situ hybridization
      (FISH). RESULTS: Increased copies of X chromosome were observed in all samples,
      and four signals of hybridization were of the major type. CONCLUSIONS: Increased
      copy number of X chromosome frequently occur in liver cancer. The relationship
      between copy number of X chromosome and liver cancer genesis needs further
      investigation. This study is the first of its kind determining the copy number of
      X chromosome in liver cancer by using FISH.

PMID- 14969852
TI  - Inhibition of hepatitis C virus-transfected cholangiocarcinoma by antisense
      oligodeoxynucleotide in nude mice.
AB  - BACKGROUND: The inhibitory effect of antisense oligodeoxynucleotide (asODN) on
      the replication and expression of hepatitis C virus (HCV) in vitro is not well
      elucidated. This study was to assess the effect of asODN on HCV in
      cholangiocarcinoma. METHODS: The QBC939 cells transfected by a recombinant HCV
      containing HCV core gene cloned in vector of PBK-CMV (PBK-HCVC) were treated by
      14-mers phosphorothioate ODN complementary to the HCV core genomic region. The
      variation of HCVmRNA level was detected by RT-PCR. Moreover, the inhibitory
      effect of asODN was observed in nude mice. RESULTS: HCVmRNA was detected in
      transfected-QBC939 cells. The 14-mers complementary phosphorothioate ODN showed
      effective inhibition on HCVmRNA and unexpression HCVmRNA at 6 micromol/L. The
      tumorigenicity of the transfected-QBC939 cells incubated with asODN in nude mice
      was greatly inhibited. CONCLUSION: The results suggest a potential therapy of
      asODN for HCV infected cholangiocarcinoma.

PMID- 14969853
TI  - Expressions of p53 and inducible nitric oxide synthase in congenital choledochal
      cysts.
AB  - BACKGROUND: Choledochal cyst, an isolated defect unrestricted to the bile duct,
      is more appropriately regarded as the sentinel feature of a constellation of
      anomalies affecting the pancreatobiliary system. This study was to assess the
      relationship between the expression of inducible nitric oxide synthase (iNOS) and
      the p53 gene as well as the pathogenesis of choledochal cysts. METHODS: iNOS and
      p53 were detected by immunohistochemistry staining in 26 patients with congenital
      choledochal cysts. Histopathologically, hyperplasia of the mucosa of the cysts
      and the amylase level in the bile were also investigated. RESULTS: Patients with
      a high level of amylase in the bile had higher expression of iNOS than those with
      a low level of amylase. p53 protein was expressed neither in fusiform type nor in
      cystic type. The incidence of mucosal hyperplasia was significantly higher in the
      fusiform type than that in the cystic type. CONCLUSIONS: Higher expression of
      iNOS may participate in hyperplasia and carcinogenesis of the mucosa of
      choledochal cysts. The regurgitation of pancreatic juice into the biliary system
      might induce mucosal hyperplasia of the biliary tract and inflammatory reaction.
      In preventing regurgitation-caused hyperplasia and malignancy of the bi-liary
      tract, early surgery is important for children with congenital choledochal cysts.

PMID- 14969854
TI  - Inhibitory effect of methylation inhibitor 5-aza-2-deoxycytidine on bile duct
      cancer cell line in vivo and in vitro.
AB  - BACKGROUND: Since the resection rate is low for bile duct cancer and the drugs
      used for chemotherapy are less effective, we studied the inhibitory effects of 5
      aza-2-deoxycytidine (ZdCyd) on bile duct cancer cell line QBC939 in vivo and in
      vitro and its possibility in clinical treatment. METHODS: The survival and
      apoptosis rates of QBC939 after treatment with different dose of ZdCyd were
      detected by methyl thiazoy tetrazolium (MTT) and flow cytometry. The cooperative
      effect of ZdCyd with other chemotherapeutic drugs was also studied with MTT. The
      cancer cells were transplanted into nude mice, which were pre-treated with ZdCyd
      after tumor occurrence. RESULTS: ZdCyd decreased the cell survival rate, blocked
      the cell cycle at G1 phase, and increased the apoptosis rate. These effects were
      dose and time-dependent. ZdCyd also increased the anti-tumor effects of other
      chemotherapeutic drugs when used in combination. The tumor occurrence rate was
      lower in the ZdCyd pre-treated cells than in the untreated cells in nude mice,
      and ZdCyd was found to inhibit tumor growth. CONCLUSION: ZdCyd can inhibit the
      growth of QBC939 in vivo and in vitro through induction of cell apoptosis and has
      the cooperative effect on bile duct cancer cell when it is used with other
      chemotherapeutic drugs.

PMID- 14969855
TI  - Intraductal ultrasonography and endoscopic retrograde cholangiography in
      diagnosis of extrahepatic bile duct stones: a comparative study.
AB  - BACKGROUND: Intraductal ultrasonography (IDUS) is highly accurate in detection of
      extrahepatic bile duct stones. This study was to compare the accuracy of IDUS and
      endoscopic retrograde cholangiography (ERC) in the diagnosis of extrahepatic bile
      duct stones. METHODS: Thirty patients suspected of extrahepatic bile duct stones
      on B ultrasonography, CT, or MRI were enrolled for study. ERC was performed using
      a Fujinon duodenoscope (ED-410XT, ED-410Xu), then IDUS was done by inserting a
      Fujinon microprobe (PL2220-15) through the endoscopic biopsy channel to detect
      the extrahepatic bile duct. Finally stones in the extrahepatic bile duct were
      detected and extracted by endoscopic sphincterotomy (EST). RESULTS: Among the 30
      patients, 26 were diagnosed as having cholelithiasis accurately through ERC. In
      one patient the stone detected by ERC was really floccule. Misdiagnosis happened
      in 2 patients with extrahepatic bile duct stones. So the overall accuracy and
      sensitivity of ERC in the diagnosis of extrahepatic bile duct stones were 86.7%
      (26/30) and 92.9% (26/28) respectively. In contrast, IDUS showed the results of
      diagnosis were in consistent with those of EST stone extraction. Its accuracy and
      sensitivity in the diagnosis of extrahepatic bile duct stones were 100% (30/30)
      and 100% (28/28) respectively. CONCLUSION: IDUS which is superior to ERC in
      diagnosing extrahepatic bile duct stones can avoid the visual error of ERC.

PMID- 14969856
TI  - Expression of the bacterial gene in gallbladder carcinoma tissue and bile.
AB  - BACKGROUND: The major causive factors of gallbladder carcinoma are very complex.
      Cholecystitis with gallstone was reported one of the most important factors. Many
      research revealed that cholecystitis or gallstone can give rise to epithelial
      hyperplasia of gallbladder mucusa or canceration secondarily. In this study, 46
      patients were detected in order to find the relationship between infection of
      different bacteria and formation of gallbladder carcinoma. METHODS: Using the
      common gene primer of bacteria 16S ribosomal RNA (rRNA), we detected bacterial
      gene fragments of gallbladder carcinoma tissues in 46 patients by polymerase
      chain reaction (PCR). Relative bile was also detected by PCR in 18 patients who
      underwent operations, including U-tube drainage (1), right or left biliary tube
      drainage (4), radical cholecystectomy (9), and cholecystorrhaphy (4). The tissue
      fragments of gallbladder carcinoma from the remaining 28 patients were paraffin
      slices. RESULTS: The positive rate of bacterial DNA in gallbladder carcinoma
      tissue was 78.3% (36/46). The sequence of 16S ribosomal RNA gene fragments
      amplified by PCR was approximately 371 base pairs (bp). Multiple kinds of
      standard bacterial gene fragments obtained from 36 patients included
      Colibacillus, B.fragilis, Klebsiella, C.perfringens and Clostridium, with a
      positive rate of 78.3% (36/46). Among the 36 patients, 14 patients with
      gallbladder carcinoma received operation and their relative bile at operation was
      detected bacterial gene fragments with a positive rate of 77.8% (14/18). This
      result was close to that in gallbladder carcinoma tissues. CONCLUSIONS: Our
      results suggested that there might be a relationship between occurrence of
      gallbladder carcinoma and infection of different kinds of bacteria, especially
      anaerobic bacteria C.perfringens. This reminds us that the gallbladder mucosa
      stimulated by anaerobic and aerobic bacteria might be the principal cause for the
      development of carcinoma.

PMID- 14969857
TI  - Anomalous pancreaticobiliary junction: image analysis and treatment principles.
AB  - BACKGROUND: Anomalous pancreaticobiliary junction is often associated with
      biliary tract carcinoma and acute pancreatitis. We assessed the value of image
      analysis in the diagnosis of patients with anomalous pancreaticobiliary junction
      (APBJ) and the principles for the treatment of APBJ. METHODS: Sixty-four patients
      with APBJ were subjected to ultrasound imaging, endoscopic retrograde
      cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography
      (MRCP) before surgery. The diagnostic accuracy of image analysis and their
      surgical outcomes were evaluated retrospectively. RESULTS: On ERCP and MRCP, the
      length of the common channel was calculated to be 15 mm or longer in all
      patients, and the angle of the junction was more than 75 degree in 49 (76.6%) of
      the 64 patients. Of the 64 patients, 28 were defined of pancreatic duct type (P
      C) (28/64, 43.75%), 32 bile duct type (C-P) (32/64, 50%), and 4 common channel
      type (4/64, 6.25%). CONCLUSIONS: Patients with APBJ are often associated with
      biliary tract and pancreatic diseases, and early detection and correct surgical
      treatment could avoid serious complications. ERCP and MRCP are accurate in the
      diagnosis of APBJ.

PMID- 14969858
TI  - One-layer pancreaticojejunostomy for prevention of pancreatic fistulae.
AB  - BACKGROUND: Anastomotic leakage at the pancreaticojejunostomy remains a common
      and dreaded complication after pancreaticoduodenectomy. This study was to
      introduce a method for lowering the mortality, morbidity, and other postoperative
      complications after pancreaticoduodenectomy. METHODS: From January 1991 to
      December 2001, twenty-six patients were treated using one-layer
      pancreaticojejunostomy. The mean age of these patients was 52.3 years. Some of
      these patients were complicated by hypoproteinemia, anemia and jaundice. All
      patients were subjected to pancreaticoduodenectomy, reconstruction of the
      digestive tract by Child's method, and one-layer or Braun's anastomosis after
      pancreaticojejunostomy, choledochojejunostomy, and gastrojejunostomy. RESULT: No
      death and pancreatic fistula were observed after operation. CONCLUSION: One-layer
      pancreaticojejunostomy is simple and safe.

PMID- 14969859
TI  - Effects of human umbilical cord serum on proliferation and insulin content of
      human fetal islet-like cell clusters.
AB  - BACKGROUND: Type 1 diabets is an autoimmune disease caused by the destruction of
      pancreatic beta-cell with an increased incidence worldwide in the closing decades
      of the 20th century. This study was to investigate the effects of human umbilical
      cord serum (UCS) on the proliferation and function of human fetal islet-like cell
      clusters (ICCs) in vitro. METHODS: Eight fresh pancreatic glands obtained after
      induction of labor with water bag were mildly exposed to collagenase V, and the
      digested cells were cultured in a RPMI-1640 medium plus 10% pooled UCS or fetal
      calf serum (FCS) to permit cells attachment and outgrowth of ICCs. RESULTS: In 8
      consecutively explanted glands, development and proliferation of ICCs were
      observed. In the presence of FCS, the outgrowth of ICC took place on the top of a
      fibroblast monocellular layer. UCS affected less growth of fibroblasts and
      increased the formation of ICCs about four-fold compared with explants from the
      same glands maintained in FCS. In both UCS and FCS, the insulin content of the
      medium was variable to a certain extent and progressively declined from day 2 to
      day 6. Dithizone-stained ICCs in UCS suggested that most cell clusters were islet
      cells (beta-cells), and the purity of islets was estimated 80%-90%. The
      ultrastructure of the cultured cells showed a large number of granule-containing
      cells, most of which were identified as beta-cells. CONCLUSION: We conclude that
      in comparison with explants with FCS, the yield of ICCs and purification of islet
      cells are markedly increased by UCS and may facilitate the proliferation of
      pancreatic beta-cells intended for islet transplantation.

PMID- 14969860
TI  - Asymptomatic process of hepatic artery thrombosis in a patient after orthotopic
      liver transplantation.
AB  - BACKGROUND: Hepatic artery thrombosis is one of the serious complications after
      liver transplantation. It will mostly cause a failure of the transplantation.
      This case of hepatic artery thrombosis showed a stable clinical course and
      minimal histological change, and now has been surviving for 4 years with normal
      liver function. We investigated the possible causes for asymptomatic hepatic
      artery thrombosis in one patient after orthotopic liver transplantation (OLT) and
      discussed the diagnosis of ischemia of OLT pathologically and clinically.
      METHODS: Liver function test, color Doppler ultrasonography, and hepatic
      arteriography were performed during the development of hepatic arteriothrombosis.
      Possible factors for the asymptomatic process of the thrombosis were analyzed.
      RESULTS: On the 4th postoperative day, thrombosis formed at the anastomotic stoma
      of the hepatic artery, and on the 11th postoperative day, the artery was
      completely occluded. Serial liver biopsies revealed intrahepatic cholestasis,
      hydropic degeneration of hepatocytes, atrophy of the biliary epithelium, and
      fibrosis in the portal area. Monitoring of liver function showed nothing abnormal
      except elevation of gamma-GT and ALP levels. On the 71st day after OLT,
      arteriography demonstrated that the hepatic artery remained completely occluded
      in addition to the establishment of collateral circulation and compensation of
      the portal vein. The patient didn't show any symptoms of arterial thrombosis.
      CONCLUSION: Collateral circulation and compensation of the portal vein are
      beneficial to allograft survival and avoidance of retransplantation after
      thrombosis of the hepatic artery. Color Doppler ultrasonography within 2 weeks
      after OLT is helpful to the early diagnosis of hepatic arteriothrombosis.

PMID- 14969861
TI  - Molecular adsorbent recirculating system in dealing with maternal Amanita
      poisoning during the second pregnancy trimester: a case report.
AB  - BACKGROUND: A 27-year-old woman in her 20th week of pregnancy was hospitalized
      because of food poisoning caused by Amanita phalloides. METHODS: Previously
      extracorporeal purification treatments with 2 times of hemodialysis plus
      hemoperfusion and a high volume therapeutic plasma exchange (PE) in addition to
      intensive medication during the first 8 days failed to improve hepatic
      encephalopathy (HE) and liver function but developed deep coma with severe blood
      chemistry and signs of threatened abortion. RESULTS: Treatments with intermittent
      molecular adsorbent recirculating system (MARS) for 3 times resulted in an
      immediate improvement of liver function and clinical symptoms including HE and
      threatened abortion until her fully recovery. When the life-threatening maternal
      illness was cured gestation went on until premature birth at the 36th week of
      pregnancy, and the infant underwent an undisturbed development. CONCLUSION: MARS
      method appears to be an optimal therapy for patients with acute liver failure
      secondary to cytoxic mushroom poisoning during pregnancy.

PMID- 14969862
TI  - Lymphoepithelial cyst of the pancreas: a case report.
AB  - BACKGROUND: Lymphoepithelial cyst of the pancreas is a rare lesion of
      undetermined pathogenesis that had been documented almost exclusively in males.
      The literature on this entity is limited to reports of single or a small number
      of cases. METHODS: The case we described herein was compared with a total of 36
      cases reported elsewhere. RESULTS: The 37 cases of lymphoepithelial cyst of the
      pancreas including our case were reviewed. Lymphoepithelial cysts have uniform
      and distinctive clinicopathologic features. Approximately 46% of the reported
      cases were asymptomatic with the lesions found incidentally, and their symptoms
      were non-specific. CONCLUSIONS: Lymphoepithelial cyst is a rare benign lesion of
      the pancreas. Fine-needle aspiration biopsy (FNAB) is a rapid and reliable
      technique that can be used as the first diagnostic step in cases of cystic
      lesions of the pancreas.

PMID- 14969863
TI  - Photosynthesis of a Scots pine shoot: a comparison of two models of shoot
      photosynthesis in direct and diffuse radiation fields.
AB  - Two models of shoot photosynthesis, the needle surface element model (SEM) and
      needle volume element model (VEM), were tested against empirical data obtained
      from measurements of the photosynthetic response of twelve Scots pine (Pinus
      sylvestris L.) shoots in direct and diffuse radiation. The models assume that
      shoot photosynthesis is obtained as the integrated response of either all needle
      surface area elements (SEM) or all needle volume elements (VEM) of the shoot. The
      models differ in that needles are treated as optically black in SEM, whereas in
      VEM radiation penetrates into the needle. The photosynthetic response of a
      surface/volume element was described as a Blackman-type curve and the
      distributions of irradiance on the elements were derived by computer simulation,
      based on a model of shoot geometry. The parameters (initial slope and maximum
      rate) of the Blackman-curve of an element were estimated iteratively by the
      method of least squares, i.e., by minimizing the residual sum of squares of
      simulated and measured rates of shoot photosynthesis. The parameter estimation
      was done separately for direct and diffuse radiation, and the models were
      evaluated based on the notion that, for the "ideal" model, the estimated
      parameter values should be the same in direct and diffuse radiation. Both models
      produced shoot photosynthesis curves that agreed well with measurements, but
      there was a discrepancy in the estimated parameter values, indicating that
      differences in the photosynthetic response of shoots in direct and diffuse
      radiation could not be explained solely on the basis of the simulated irradiance
      distributions. The agreement was, however, much better for the volume element
      model, which accounts for penetration of radiation into the needles.

PMID- 14969864
TI  - Effects of water deficit on flower opening in coffee (Coffea arabica L.).
AB  - The response of coffee (Coffea arabica L.) floral buds to different water
      deficits followed by re-irrigation was investigated. Flower opening was
      stimulated by irrigation after one period of water deficit if predawn leaf water
      potential declined below -0.8 MPa. Similar stimulation of flowering was observed
      when less severe but more prolonged water deficits (ca. -0.3 to -0.5 MPa for two
      weeks) were imposed, even if water deficit was relieved by re-irrigation several
      times during this period. Consistent results were obtained in the field and in
      two greenhouse locations. Stimulation of flower opening by water deficit followed
      by re-irrigation was restricted to buds at the "open white cluster" stage of
      development (Stage 4). Only buds at this stage exhibited development of secondary
      xylem. Split-root experiments indicated that a root signal stimulated flower
      opening, independently of predawn or midday leaf water status. Frequent
      irrigation to prevent flowering, followed by a controlled water deficit and re
      irrigation to stimulate flowering, may represent a practical method to
      synchronize flowering and shorten the harvest period in leeward coffee production
      areas in Hawaii.

PMID- 14969865
TI  - Absolute and relative growth of Douglas-fir seedlings of different sizes.
AB  - Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) seedlings of a single seed
      source were grown in a bare-root nursery for two years to produce five different
      stock types by varying spacing and transplanting treatments. They were then
      planted in the forest together with one-year-old container seedlings of the same
      seed source, which constituted a sixth treatment. Stem volume mean relative
      growth rate (R(v)) was low immediately after planting for all stock types except
      the container seedlings, and increased over the following 7.6 years. An 8-week
      greenhouse test of the six stock types showed that dry weight mean relative
      growth rate (R(w)) generally decreased with seedling dry weight, but this effect
      was less obvious after planting, because only the three smaller stock types
      showed a decrease in R(w) with size. In another experiment, bare-root Douglas-fir
      seedlings were grown at five different spacings in a nursery for two years, and
      seedlings from each spacing treatment were sorted into large or small by height.
      The resulting 10 treatments were planted in the forest and stem volumes
      determined over 6.7 years. The linear effect of nursery spacing on stem volume
      was no longer evident 3.6 years after planting, but large seedlings had greater
      stem volume than the small seedlings throughout the 6.7 years of the study. There
      was no indication that R(v) declined with time, but small seedlings had higher
      R(v) than large seedlings. Relative growth rates of two-year-old Douglas-fir were
      depressed for a year or two after planting, but then remained relatively
      constant, or increased during the ensuing 5 years. Relative growth rates of
      smaller seedlings were greater than those of larger seedlings so that relative
      biomass differences decreased with time, and the time advantage (the time
      necessary for small seedlings to reach the present biomass of large stock) of
      larger stock decreased. Absolute size differences increased with time.

PMID- 14969866
TI  - Growth, nutrition and response to water stress of Pinus pinaster inoculated with
      ten dikaryotic strains of Pisolithus sp.
AB  - Reconstituted dikaryons of Pisolithus sp. (Pers.) Coker & Couch from South Africa
      influenced growth parameters (shoot length, shoot/root ratio and leaf area),
      nutrition and physiological indicators (transpiration rate, stomatal conductance
      and xylem water potential) of maritime pine (Pinus pinaster Ait.) seedlings
      during drought and recovery from drought. Seedlings colonized with certain
      dikaryons were more sensitive to water stress and showed less mycorrhiza
      formation under water stress than seedlings colonized with other dikaryons.
      Control (uninoculated) seedlings were significantly smaller than those inoculated
      with dikaryons. Transpiration rate, stomatal conductance and xylem water
      potential varied among mycorrhizal treatments during the water stress and
      recovery periods. After rewatering, the controls and seedlings inoculated with
      dikaryon 34 x 20 had a weaker recovery in transpiration rate, stomatal
      conductance and xylem water potential than the other treatments and appeared to
      have experienced damage due to the water stress. Concentrations of various
      elements differed in the shoots of Pinus pinaster colonized by the various
      dikaryons. It is suggested that breeding of ectomycorrhizal fungi could
      constitute a new tool for improving reforestation success in arid and semi-arid
      zones.

PMID- 14969867
TI  - Localization and quantitative determination of catechins and proanthocyanidins in
      the phloem of elm and cherry.
AB  - The localization of catechins and proanthocyanidins in the phloem of elm (Ulmus
      minor Mill.) and cherry (Prunus avium L.) was determined histochemically by use
      of 4-dimethylaminocinnamaldehyde (DMACA) reagent. The two tree species showed a
      characteristic distribution of these phenols, which were most abundant in the
      phloem rays of cherry, but were largely confined to upright parenchyma cells of
      elm. Quantitative determination and qualitative separation of catechins and
      proanthocyanidins were performed using HPLC-CRD (chemical reaction detection),
      with 4-dimethylaminocinnamaldehyde as the staining reagent. Up to 14 different
      catechins and proanthocyanidins were found in both species.

PMID- 14969868
TI  - Physiology and morphology of Douglas-fir rooted cuttings compared to seedlings
      and transplants.
AB  - Cuttings of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) from three open
      pollinated families were rooted in two types of tray, and then grown for 1.5
      years in a bareroot nursery. During their second winter they were sampled
      periodically and tested for cold hardiness, dormancy status, root growth
      potential and various morphological characteristics. Two-year-old seedlings and
      transplants were tested concurrently for comparison. Rooted cuttings, seedlings
      and transplants cold hardened at similar rates during early winter, achieving the
      same level of midwinter hardiness (LT(50) = -18 degrees C) in early January.
      However, rooted cuttings remained hardier later into the spring than did
      seedlings or transplants. Rooted cuttings exhibited deeper dormancy in early
      winter than seedlings or transplants but these differences disappeared after
      January. Root growth potentials of all three stock types remained above threshold
      values established for transplants throughout winter. Rooted cuttings had greater
      stem diameter, higher stem diameter to height ratio, and greater root weight than
      either seedlings or transplants. This may reflect lower growing densities for the
      rooted cuttings. Root/shoot ratios of rooted cuttings were greater than for
      seedlings and similar to those of transplants. Rooted cuttings also had deeper
      and coarser root systems, which probably reflects lack of wrenching at the
      nursery.

PMID- 14969869
TI  - Carbon and phosphorus partitioning in Pinus serotina seedlings growing under
      hypoxic and low-phosphorus conditions.
AB  - Ten-week-old pond pine (Pinus serotina Michx.) seedlings were grown in solution
      culture at 5 or 100 microM P and under aerobic or hypoxic solution conditions.
      After 6 and 10 weeks in the treatments, changes in relative growth rate (RGR), P
      acquisition and allocation, and carbohydrate partitioning were determined by
      analyzing tissue for total P, soluble sugars and starch. Six weeks of low-P
      growth conditions decreased seedling dry weight and the ratio of shoot dry weight
      to root dry weight (S/R) by 39 and 51%, respectively, in comparison to seedlings
      from the aerobic, high-P (control) treatment. Mean RGRs of shoots in the low-P
      treatment were reduced by 33%, whereas root growth was unaffected. After 10 weeks
      of low-P growth conditions, however, both shoot and root RGRs were significantly
      reduced, and plants had lower S/R ratios than in any other treatment. Slowed
      shoot growth was accompanied by starch and nonstructural carbohydrate
      accumulation in needles, indicating that needle growth was not limited by
      carbohydrate supply. Six weeks of low-P growth conditions decreased total
      seedling P by 75%, reflecting a 97% reduction in the net uptake rate (NUR). Shoot
      NUR as a fraction of seedling NUR was also greatly reduced in the low-P
      treatment, indicating that low-P growth conditions affected P translocation to
      the shoot more than P accumulation by roots. In contrast, 6 weeks of hypoxic
      growth conditions decreased total dry weight of seedlings in the high-P treatment
      by 41% relative to their aerobic counterparts. Root growth was affected more than
      shoot growth, however, and S/R ratios increased. After 10 weeks, S/R ratios
      doubled, primarily because of the reduction in root RGR. Nevertheless, roots of
      hypoxic seedlings contained a higher percentage of total seedling P than their
      aerobic counterparts. Net P acquisition per seedling decreased by more than 50%
      under hypoxic growth conditions, as a result of reductions in both root RGR and
      seedling NUR. Starch accumulation in shoots of hypoxic seedlings reflected
      reductions both in root growth and in transport of carbohydrates to nonwoody
      roots. Carbohydrate availability did not appear to be limiting growth of hypoxic
      woody roots, which are well-aerated internally, but it may have limited metabolic
      processes in nonwoody roots of seedlings from the high-P treatment.

PMID- 14969870
TI  - Laser microprobe mass analysis (LAMMA) of aluminum and lead in fine roots and
      their ectomycorrhizal mantles of Norway spruce (Picea abies (L.) Karst.).
AB  - Fine roots and ectomycorrhizal root tips were sampled in a Norway spruce (Picea
      abies (L.) Karst.) stand in the eastern part of the Belgian Ardennes. The
      cellular and partly subcellular localizations of aluminum and lead were
      identified by the micro-analytical laser microprobe mass analysis (LAMMA)
      technique. In fine roots with secondary structure, localization of aluminum was
      limited to the peripheral cell layers. Lead was found in the outer layers, and
      also in the primary phloem. Aluminum penetrated the mycorrhizal mantle, but lead
      was seldom detected in ectomycorrhizae.

PMID- 14969871
TI  - Water relations and gas exchange of Acer saccharum seedlings in contrasting
      natural light and water regimes.
AB  - Field measurements were made of leaf photosynthesis (A), stomatal conductance (g)
      and leaf water relations for sugar maple (Acer saccharum Marsh.) seedlings
      growing in a forest understory, small gap or large clearing habitat in
      southwestern Wisconsin, USA. Predawn water status, leaf gas exchange and
      plasticity in field and laboratory water relations characteristics were compared
      among contrasting light environments in a wet year (1987) and a dry year (1988)
      to evaluate possible interactions between light and water availability in these
      habitats. Leaf water potentials (Psi(leaf)) at predawn and midday were lower for
      clearing than gap or understory seedlings. Acclimation of tissue osmotic
      potentials to light environment was observed among habitats but did not occur
      within any of the habitats in response to prolonged drought. During a summer
      drought in 1988, decreases in daily maximum g (g(max)) and maximum A (A(max)) in
      clearing seedlings were correlated with predawn Psi(leaf), which reached a
      seasonal minimum of -2.0 MPa. Under well-watered conditions, diurnal fluctuations
      in Psi(leaf) of up to 2.0 MPa in clearing seedlings occurred along with large
      midday depressions of A and g. In a wet year, strong stomatal responses to leaf
      to-air vapor pressure difference (VPD) in sunny habitats were observed over nine
      diurnal courses of gas exchange measurements on seedlings in a gap and a
      clearing. Increasing stomatal limitations to photosynthesis appeared to be
      responsible for the reduction in A at high VPD for clearing seedlings. In
      understory seedlings, however, low water-use efficiency and development of leaf
      water deficits in sunflecks was related to reduced stomatal limitations to
      photosynthesis relative to seedlings in sunny habitats. Predawn Psi(leaf) and VPD
      appear to be important factors limiting carbon assimilation in sugar maple
      seedlings in light-saturating irradiances, primarily through stomatal closure.
      The overall results are consistent with the idea that sugar maple seedlings
      exhibit "conservative" water use patterns and have low drought tolerance. Leaf
      water relations and patterns of water use should be considered in studies of
      acclimation and species photosynthetic performance in contrasting light
      environments.

PMID- 14969872
TI  - Carbon exchange rates, chlorophyll content, and carbohydrate status of two forest
      tree species exposed to carbon dioxide enrichment.
AB  - Seedlings of yellow-poplar (Liriodendron tulipifera L.) and white oak (Quercus
      alba L.) were exposed continuously to one of three CO(2) concentrations in open
      top chambers under field conditions and evaluated after 24 weeks with respect to
      carbon exchange rates (CER), chlorophyll (Chl) content, and diurnal carbohydrate
      status. Increasing the CO(2) concentration from ambient to +150 or +300 microl l(
      1) stimulated CER of yellow-poplar and white oak seedlings by 60 and over 35%,
      respectively, compared to ambient-grown seedlings. The increases in CER were not
      associated with a significant change in stomatal conductance and occurred despite
      a reduction in the amounts of Chl and accessory pigments in the leaves of plants
      grown in CO(2)-enriched air. Total Chl contents of yellow-poplar and white oak
      seedlings grown at +300 microl l(-1) were reduced by 27 and over 55%,
      respectively, compared with ambient-grown seedlings. Yellow-poplar and white oak
      seedlings grown at +300 microl l(-1) contained 72 and 67% more morning starch,
      respectively, than did ambient-grown plants. In contrast, yellow-poplar and white
      oak seedlings grown at +300 microl l(-1) contained 17 and 27% less evening
      sucrose, respectively, than did plants grown at ambient CO(2) concentration.
      Diurnal starch accumulation and the subsequent depletion of sucrose contributed
      to a pronounced increase in the starch/sucrose ratio of plants grown in CO(2)
      enriched air. All seedlings exhibited a substantial reduction in dark respiration
      as CO(2) concentration increased, but the significance of this increase to the
      carbohydrate status and carbon economy of plants grown in CO(2)-enriched air
      remains unclear.

PMID- 14969873
TI  - Storage and internal cycling of nitrogen in relation to seasonal growth of Sitka
      spruce.
AB  - Three-year-old clonal cuttings of Picea sitchensis (Bong.) Carr. were grown for
      two years (1988-1989) in sand irrigated with a nutrient solution containing
      either 1.0 mol N m(-3) (low N) or 6.0 mol N m(-3) (high N) NH(4)NO(3). In 1988,
      all the N provided was enriched with (15)N to 4.95 atom % (labeled N). In 1989, N
      was supplied with (15)N at natural abundance (unlabeled N). The recovery of
      unlabeled and labeled N in new foliage was used to quantify the internal cycling
      of N. In the high-N treatment, trees had two flushes of shoot growth and a period
      of rapid root growth, which coincided with the second flush of shoot growth in
      August. The timing of root growth and the first flush of shoot growth was similar
      in the low-N treatment, but there was no second flush of shoot growth and a
      greater proportion of biomass was recovered in roots. By November 1989, the
      root/needle dry matter ratio was 1.95 for the low-N trees and 1.36 for the high-N
      trees. Nitrogen was stored overwinter in roots and current-year needles. During
      the first six weeks of growth in the spring of 1989, stored N was remobilized for
      new foliage growth. Subsequent growth depended on root uptake of N.
      Remobilization of stored N was apparently not affected by the current N supply,
      because the amount of unlabeled N recovered in foliage produced in 1988 was the
      same for both N treatments. During 1989, the proportion of (15)N remobilized from
      roots relative to that from leaves produced in 1988 was greater in low-N trees
      than in high-N trees. In the autumn of both years, there was rapid uptake of N
      into roots and current-year needles. The effects of N supply on tree growth and
      nitrogen use efficiency are discussed in terms of the capacity for both N storage
      and internal cycling.

PMID- 14969874
TI  - Nutrient retranslocation within the foliage of Pinus sylvestris.
AB  - During the period 1983-1987, retranslocation of N, P, K, Ca, Mg, Mn, Zn, Fe, B
      and Al within the foliage of Scots pine (Pinus sylvestris L.) was studied in
      sapling, pole-stage and mature stands in eastern Finland. Needle concentrations
      of the mobile nutrients N, P, and K varied seasonally because of retranslocation.
      In unfertilized plots, needle contents of N, P and K decreased 62-92% during
      senescence and needle dry weight decreased 19-51%. In some years, needle contents
      of Ca, Mn, Zn, Fe, B and Al increased during senescence. Retranslocation was more
      efficient from needles with greater dry weight. In the fertilized, pole-stage
      stand, needle dry weight did not decrease at senescence four years after
      fertilization and nutrient content decreased less than in the other years. In the
      mature stand, there were no clear differences in needle dry weight and nutrient
      changes during senescence between years or between unfertilized and fertilized
      plots.

PMID- 14969875
TI  - Nutrient dynamics in singleleaf pinyon (Pinus monophylla Torr & Frem.) needles.
AB  - Nutrient retranslocation from existing foliage of singleleaf pinyon pine (Pinus
      monophylla Torr. & Frem.) did not meet the nutrient demands of new needles on the
      same branch. Singleleaf pinyon pines, with an average age of 177 years, located
      at an elevation of 2300 m on a ridge in The Sweetwater Range in Nevada, USA
      retained needles for 18 or more years and increased needle number per branch by
      17-18% annually. With age, needles gained weight and accumulated Ca, Mg, Fe, Zn,
      P, and Mn. The amount of N per needle showed no consistent trend with needle age.
      Only Cu and K declined in concentrations and amounts with needle age and these
      differences were not statistically significant. Retranslocation of nutrients at
      needle abscission could provide only 2 to 13% of the N, P, K, Fe, Cu, and Mg
      required by new needles. We conclude that nutrient capital in existing foliage
      constitutes a long-term nutrient reserve for the tree rather than a mobile
      nutrient pool.

PMID- 14969876
TI  - Patterns in aboveground carbon allocation and tree architecture that favor stem
      growth in young Scots pine from high latitudes.
AB  - The production and allocation of aboveground biomass and the characteristics of
      tree architecture were examined in eight-year-old Scots pine (Pinus sylvestris
      L.). Considerable among-tree variation existed in tree architecture, total
      aboveground dry mass production, and dry mass partitioning among tree parts. A
      linear relationship existed between needle and branch mass. Stem mass was
      directly proportional to tree height, which in turn was directly proportional to
      the allocation ratio between stem mass and total needle + branch mass production.
      The architectural characteristics that were related to a high proportional
      allocation to stem and high stemwood production were a large mean shoot volume,
      large mean number of branches per whorl, long needle retention and a high crown
      length/crown width ratio. Individual trees were found that combined high stemwood
      production with both high harvest index and high stemwood specific gravity.

PMID- 14969877
TI  - Carbon and nitrogen partitioning in peach/plum grafts.
AB  - Modifications in root-shoot relationships induced by graft incompatibility were
      studied in peach/plum graft combinations by means of carbohydrate and nitrogen
      analyses and isotope labeling. Mobilization of stored carbon, phloem transport of
      carbon, and mobilization, assimilation and distribution of nitrogen were studied
      in one compatible peach/plum graft (Prunus persica L. Batsch cv. springtime
      grafted on Prunus cerasifera L. Ehrh cv. myrobalan P 2032) and one incompatible
      graft (Prunus persica L. Batsch cv. Springtime grafted on Prunus cerasifera L.
      Ehrh cv. myrobalan P 18) for 89 days after grafting. Carbon and nitrogen reserves
      were mobilized in the rootstock in both graft combinations during the first 78
      days following grafting. After that, sorbitol concentration was lower in the
      roots of the incompatible graft than in the roots of the compatible graft,
      whereas soluble sugars and starch accumulated in the peach scion of the
      incompatible graft. In both graft types, carbon was allocated mainly to the
      scion. Labeling with (13)CO(2) from 78 to 81 days after grafting showed that
      carbon partitioning among the different plant organs was only slightly affected
      by graft incompatibility. Carbohydrate concentrations provided indirect evidence
      that carbon transfer to the roots was hindered in the incompatible graft.
      Labeling with (15)NO(3) showed that nitrogen distribution and the rate of
      nitrogen assimilation were similar in the two graft combinations from 57 to 78
      days after grafting. Nitrogen assimilation in the incompatible graft ceased 78
      days after grafting, whereas it continued in the compatible graft.

PMID- 14969878
TI  - Influence of nitrogen fertilization on minerals, carbohydrates, amino acids and
      phenolic compounds in beech (Fagus sylvatica L.) leaves.
AB  - Beginning in 1985, plots in a 120-year-old beech (Fagus sylvatica L.) stand in
      the province of Scania, southern Sweden were fertilized annually with ammonium
      nitrate. In August 1989, leaves from both fertilized and unfertilized trees were
      analyzed for mineral nutrients, soluble carbohydrates, amino acids and phenolic
      compounds. Leaf concentrations of total nitrogen were increased by N
      fertilization. Ammonium was not detected in the leaves, but NO(3) (-) was
      increased by up to 65% as a result of N fertilization. Nitrogen fertilization
      decreased foliar concentrations of P and Cu, leading to a nutrient imbalance
      relative to N. Of the free amino acids, glutamic acid and aspartic acid
      predominated and, together with glutamine and asparagine, were significantly
      increased by N fertilization. The concentrations of amides were 2-4 times higher
      in fertilized trees than in unfertilized trees. Soluble carbohydrates did not
      change in response to N fertilization, but total phenolic compounds decreased
      markedly. The reduced concentration of phenolics may explain the greater
      susceptibility to parasite attacks of trees exposed to N deposition and excess N.

PMID- 14969879
TI  - Long-term respiration in relation to growth and maintenance processes of the
      aboveground parts of a hinoki forest tree.
AB  - Over a three-year period, CO(2) exchange rates were measured continuously on the
      aboveground parts of a 13-year-old hinoki (Chamaecyparis obtusa (Sieb. et Zucc.)
      Endl.) tree in the field, using an open gas-exchange system tracking ambient
      temperature. The relationship between daily aerial respiratory consumption and
      daily gross production, which was analyzed monthly, closely resembled McCree's
      equation. The value of the coefficient of growth respiration ranged between 0.0
      in winter and 0.16 in summer and increased with increasing monthly mean
      temperature. A clockwise loop was observed for monthly change in the relationship
      between the coefficient of growth respiration and temperature. Maintenance
      respiration could be formulated as a power function of aboveground dry weight.
      The exponent of the equation ranged from 0.3 to 1.1. A value of 1.1 in May and
      June, when trees were growing most actively, indicated that maintenance
      respiration was directly proportional to aboveground weight. In March, April,
      July, and August, maintenance respiration was not proportional to aboveground
      weight, but it was closely proportional to surface area. The exponent value
      exhibited seasonal change with a clockwise loop in response to monthly average
      temperature. During the dormant season, respiration was used only for maintenance
      purposes, whereas during the growing season both growth and maintenance
      respiration occurred. Annual growth and maintenance respiration increased with
      increasing tree age. The average annual contribution to total respiratory
      consumption was 21% for growth respiration and 79% for maintenance respiration.

PMID- 14969880
TI  - Water stress, photosynthesis and early growth patterns of cuttings of three
      Populus clones.
AB  - Photosynthetic attributes, leaf area and early root growth patterns were studied
      in three Populus clones to identify traits associated with superior growth
      potential on sites where water could be a limiting factor. It was found that
      early root growth and superior leaf area production were more closely related to
      growth potential than were photosynthetic capacity or carboxylation efficiency. A
      hybrid clone of Populus nigra var. charkowiensis (syn. P. nigra var.
      plantierensis) x P. nigra cv. 'Incrassata' (NE308) had more leaf area production
      and greater root system development in both wet and dry soil than did a P.
      trichocarpa clone (T6) and a P. balsamifera clone (B3). Despite greater above-
      and below-ground productivity, plants of clone NE308 had significantly lower
      photosynthetic capacity and carboxylation efficiency and a slightly higher CO(2)
      compensation point than plants of clones T6 and B3. Rapid early leaf and root
      growth appear to be key attributes associated with productivity in these clones
      regardless of soil water availability.

PMID- 14969881
TI  - Solar irradiance and the development of endomycorrhizal green ash seedlings.
AB  - We investigated the effects and interaction of four irradiances, 37, 53, 70 and
      100% full sunlight, and the endomycorrhizae Glomus macrocarpum and Glomus
      fasciculatum on the development of seedlings of Fraxinus pennsylvanica Marsh. At
      all irradiances, mycorrhizal seedlings were taller and larger in diameter than
      nonmycorrhizal seedlings. Seedlings inoculated with G. macrocarpum showed the
      best height growth at 70% or less of full sunlight, whereas seedlings inoculated
      with G. fasciculatum grew best at 37 and 53% full sunlight. Leaf area was
      greatest in shaded seedlings and was enhanced by mycorrhizal inoculation.
      Shoot/root ratios were greater for mycorrhizal than for nonmycorrhizal seedlings.
      At intermediate light intensities, percent root length colonized was greatest,
      whereas the concentrations of soluble sugar and starch in roots were at
      intermediate levels.

PMID- 14969882
TI  - Growth of Eucalyptus marginata (Jarrah) seedlings in a greenhouse in response to
      shade and soil temperature.
AB  - The effects of shade and soil temperature on growth of Eucalyptus marginata Donn
      ex Sm (jarrah) seedlings were studied in greenhouse experiments. Plant dry weight
      and that of all plant parts declined in response to shade, as did root/shoot
      ratio. Plant leaf area was less in unshaded plants than in plants grown in shade,
      and specific leaf area increased with shade. Unshaded seedlings had a higher
      light-saturated rate of photosynthesis, a higher light compensation point and a
      higher light saturation point than seedlings grown in 70% shade. The relationship
      between plant dry weight and leaf dry weight was independent of shading, whereas
      the relationship between plant dry weight and plant leaf area was dependent on
      shading. Therefore, leaf dry weight may be a better predictor of biomass
      production than leaf area in forest stands where shade is likely to affect growth
      significantly. Soil temperature had a significant effect on the growth of all
      plant parts except cotyledons. Total plant growth and shoot growth were maximal
      at a soil temperature of 30 degrees C, but root growth had a slightly lower
      temperature optimum such that the root/shoot ratio was highest at 20 degrees C.
      Roots grown at 15 degrees C were about 30% shorter per unit of dry weight than
      roots grown at 20 to 35 degrees C. We conclude that increases in irradiance and
      soil temperature as a result of overstory removal in the forest will cause
      significant increases in growth of E. marginata seedlings, but these increases
      represent a relatively small component of the growth response to overstory
      removal.

PMID- 14969883
TI  - Maturation in larch: age-related changes in xylem development in the long-shoot
      foliage and the main stem.
AB  - As the meristems of eastern larch (Larix laricina (Du Roi) K. Koch) mature, they
      produce long-shoot foliage with progressively higher chlorophyll content and net
      photosynthesis and progressively lower specific leaf area (Hutchison et al.
      1990). Despite the apparent increase in foliar vigor, both shoot height and
      diameter growth rates declined during maturation. These changes were associated
      with changes in xylem morphology of the vascular tissue of both the long-shoot
      foliage and the main stem. Although the number of xylem cells remained constant
      in a cross section of the foliage, their diameters increased with age. With
      increasing maturation, the same number of xylem cells were produced per radial
      file in the annual rings of the main stem, but their radial diameters decreased,
      which accounted for the decrease in diameter growth. There was no change in
      tracheid length during maturation. We conclude that the decrease in growth rate
      with increased maturation is not due to a decrease in physiological vigor of the
      foliage, but is a function of reduced sink strength of the growing shoots.

PMID- 14969884
TI  - A growth model of a single sugi (Cryptomeria japonica) tree based on the dry
      matter budget of its aboveground parts.
AB  - Growth of a single sugi (Cryptomeria japonica (L.f.) D. Don.) tree was analyzed
      on the basis of a dry matter budget. The aboveground net production rate and
      death rate were defined as the anabolic rate and catabolic rate, respectively.
      Growth rate of aboveground tree weight, v(w) (kg(dw) year(-1)), was defined as
      follows: v(w) = v(p) - v(d) (1) where v(p) (kg(dw) year(-1)) is the aboveground
      net production rate and v(d) (kg(dw) year(-1)) is the aboveground death rate. The
      value of v(d) is obtained by measuring the monthly clippings of new dead leaves
      and branches attached to a sample tree. The value of v(w) was calculated as the
      annual difference in the estimated aboveground tree weight, w(T) (kg(dw)).
      Finally, the value of v(p) was estimated as the sum of the values of v(d) and
      v(w). The following allometric relationships were found between v(p) and w(T) and
      between v(d) and w(T): v(p) = aw(T) (alpha), v(d) = bw(T) (beta) (2). Combining
      Equations 1 and 2 gives a growth equation, Bertalanffy's equation, of the sample
      tree. dw(T)/dt = v(w) = aw(T) (alpha) - bw(T) (beta) (3). Because the growth
      curve of w(T) was derived from Equation 3, the analysis of the growth of w(T) is
      based on direct measurement of the dry matter budget.

PMID- 14969885
TI  - Influence of photoperiod and temperature on frost hardiness and free amino acid
      concentrations in black spruce seedlings.
AB  - We investigated the effects of a 4-week exposure to an 8-h or 18-h photoperiod at
      5 or 25 degrees C on the development of hardiness to -20 degrees C and the
      accumulation of proline (Pro), arginine (Arg) and tryptophan (Trp) in shoots of
      black spruce (Picea mariana (Mill.) B.S.P.) seedlings. The greatest degree of
      hardening to -20 degrees C occurred in seedlings exposed to an 8-h photoperiod at
      25 degrees C, and some hardening occurred in seedlings exposed to 5 degrees C in
      either an 8-h or 18-h photoperiod. Proline accumulated in shoots in response to 5
      degrees C and either an 8-h or 18-h photoperiod, whereas Trp accumulated in
      response to an 8-h photoperiod at either temperature, and Arg only accumulated in
      shoots in the 5 degrees C + 8-h photoperiod treatment. Only the accumulation of
      Trp was significantly related to the degree of hardiness to -20 degrees C.

PMID- 14969886
TI  - Responses of loblolly pine seedlings to elevated CO(2) and fluctuating water
      supply.
AB  - Osmotic adjustment of loblolly pine (Pinus taeda L.) seedlings to fluctuating
      water supply in elevated CO(2) was investigated. Seedlings were grown in
      controlled-environment chambers in either 350 or 700 micro l l(-1) CO(2) with
      weekly watering for four months, after which they were either watered weekly
      (well-watered treatment) or every two weeks (water-stress treatment) for 59 days.
      Osmotic adjustment was assessed by pressure-volume analysis of shoots and by
      analysis of soluble carbohydrates and free amino acids in roots during the last
      drying cycle. In well-watered seedlings, elevated CO(2) increased the
      concentration of soluble sugars in roots by 68%. Water stress reduced the soluble
      sugar concentration in roots of seedling growing in ambient CO(2) to 26% of that
      in roots of well-watered seedlings. Elevated CO(2) mitigated the water stress
      induced decrease in the concentration of soluble sugars in roots. However, this
      was probably due, in part, to carbohydrate loading during the first four months
      when all seedlings were grown in the presence of a high water supply, rather than
      to osmotic adjustment to water stress. Water stress caused a doubling in the
      concentration of free primary amino acids in roots, whereas elevated CO(2)
      reduced primary amino acid and nitrogen concentrations to 32 and 74%,
      respectively, of those in roots of seedlings grown in ambient CO(2). There was no
      indication of large-scale osmotic adjustment to water stress or that elevated
      CO(2) enhanced osmotic adjustment in loblolly pine.

PMID- 14969887
TI  - Crown architecture of stand-grown sugar maple (Acer saccharum Marsh.) in the
      Adirondack Mountains.
AB  - Leaf and crown morphology of shade-tolerant sugar maple (Acer saccharum Marsh.)
      were examined to test the hypotheses (1) that leaf area exhibits significant
      plasticity both within and between crown classes and individual tree crowns and
      (2) that leaf area is accurately predicted from estimates of crown volume. A
      total of 18 trees, ranging from 3.3 to 43.4 cm dbh, were felled and dissected
      into upper, middle, lower, and below-crown layers, for measurements of leaf,
      bark, and xylem dimensions. For dominant trees only, bark thickness and xylem
      radii were higher within the crown than below the crown. Cumulative leaf area
      index increased with decreasing stratum height at similar rates in all trees,
      except for two trees that were located in the understory. Area leaf weight
      declined with decreasing stratum height within the crown of all except four
      overstory trees. These four trees showed an increase with decreasing stratum
      height, i.e., leaves were heavier per unit area in the lower crown stratum and
      below the crown than they were at mid-crown. Within-tree leaf area density was
      usually higher in the upper crown of overstory trees and in the lower crown of
      understory trees. Total crown volume was the best predictor of whole-tree leaf
      area, but it was only slightly better than dbh.

PMID- 14969888
TI  - Diurnal pattern of leaf extension in Salix viminalis relates to the difference in
      leaf turgor before and after stress relaxation.
AB  - Diurnal variations in leaf extension and turgor relaxation were measured in young
      willow leaves (Salix viminalis L.). Turgor relaxation was calculated from
      measurements of xylem water potential and osmotic potential of whole, detached
      leaves that were incubated, without loss of water, under controlled conditions.
      There were clear diurnal variations in leaf extension and in leaf turgor
      relaxation and the diurnal pattern of the difference in leaf turgor before and
      after relaxation was in phase with that of leaf extension. The extent to which
      leaf turgor after relaxation may be related to threshold turgors for growth and
      the possible importance of leaf turgor during leaf extension are discussed.

PMID- 14969889
TI  - Photosynthesis of oak leaves under water stress: maintenance of high
      photochemical efficiency of photosystem II and occurrence of non-uniform CO(2)
      assimilation.
AB  - Net CO(2) assimilation rates (A), stomatal conductance to water vapor (g(w)),
      photosynthetic O(2) evolution in 5% CO(2) (A(max)) and photochemical efficiency
      of photosystem II were monitored in leaves of young oak saplings (Quercus petraea
      Matt. Liebl.) in response to increasing drought. Both A and g(w) declined rapidly
      as soon as predawn leaf water potential dropped below -1.0 MPa. The calculated
      intercellular concentration of CO(2) first declined and then increased again as
      drought intensity increased, suggesting that both stomatal closure and a
      decreased ability of mesophyll chloroplasts to fix available CO(2) were involved
      in the drought-induced reductions in A and g(w). However, this assumption was not
      supported by the observations that, with increasing drought, the decline in
      A(max) was limited, and the photochemistry of photosystem II and the quantum
      yield of light-driven electron transport remained stable. Autoradiograms of
      (14)CO(2)-fed leaves revealed non-uniform assimilation rates during water stress.
      The consequences of a potential artifact induced by this patchiness on the
      calculation of intercellular CO(2) concentration are discussed.

PMID- 14969890
TI  - Cold tolerance and water content of current-year red spruce foliage over two
      winter seasons.
AB  - Red spruce (Picea rubens Sarg.) in high elevation forests of northeastern North
      America suffers from frequent and severe winter injury, leading to apical
      dieback, decreased growth, and high mortality. To examine the role of winter
      desiccation and freezing injury in winter damage, weekly assessments of cold
      tolerance and water content were made on current-year foliage collected from
      native red spruce trees at a high elevation site over two winter seasons. In both
      years, foliage maintained high water contents and adequate cold tolerance;
      nonetheless, slight to moderate injury was observed each year on some trees.
      Despite brief thaw periods each winter, no mid-winter dehardening sufficient to
      put foliage at risk of freezing injury was evident. These findings suggest that,
      at least in some years, winter injury to current-year red spruce foliage is
      produced by a mechanism other than desiccation or absolute low temperatures.

PMID- 14969891
TI  - Midwinter needle temperature and winter injury of montane red spruce.
AB  - To assess the role of solar warming and associated temperature fluctuations in
      the winter injury of sun-exposed red spruce foliage, we used fine wire
      thermocouples to monitor midwinter needle temperature in the upper canopy of
      mature red spruce trees over two winters. In 1989-1990, 15-min mean temperatures
      were recorded for six needles in a single tree. In 1990-1991, 10-min mean
      temperatures of six needles in one tree, and 1-min mean temperatures of seven
      needles in a second tree were recorded during rapid temperature changes. Warming
      was more frequent and greatest on terminal shoots of branches with a south to
      southwest aspect. The maximum rise above ambient air temperature exceeded 20
      degrees C, and the maximum one minute decrease in temperature was 9 degrees C,
      with maximum rates of 0.8 and 0.6 degrees C min(-1) sustained over 10- and 15-min
      intervals, respectively. These data demonstrate that red spruce is subject to
      rapid temperature fluctuations similar to those known to produce visible injury
      in American aborvitae, a much hardier species. We concluded that solar warming to
      temperatures above the freezing point was unlikely to result in dehardening and
      subsequent freezing injury, because warming was infrequent, of short duration,
      and did not always raise needle temperature above the freezing point. Parts of
      branches and some individual shoots were frequently covered by snow or rime that
      may have prevented injury by reducing the frequency or intensity of needle
      temperature fluctuations. Radiation load on exposed shoots may have been
      increased by reflection of short wave radiation from snow and rime deposits on
      surrounding surfaces, which would exacerbate temperature fluctuations.

PMID- 14969892
TI  - Assimilation and stomatal conductance responses of red spruce to midwinter frosts
      and the constituent ions of acid mist.
AB  - Red spruce (Picea rubens Sarg.) seedlings growing outside in open-top chambers
      were sprayed twice weekly with artificial mists at either pH 2.5 or 5.6, for five
      months during the 1988 growing season. The mists contained one of the following:
      water, pH 5.6 (control); (NH(4))(2)SO(4), pH 5.6; NH(4)NO(3), pH 5.6; HNO(3), pH
      2.5; H(2)SO(4), pH 2.5; or (NH(4))(2)SO(4) + NH(4)NO(3), pH 2.5. During January
      1989, the light responses of assimilation and stomatal conductance were assessed
      in the laboratory following a 4-day equilibration at 12 degrees C. The aerial
      portions of the intact trees were then subjected to a mild (-10 degrees C) frost
      for three hours during the night and the rate of recovery of light-saturated
      assimilation (A(max)) was determined the following day using the same branches as
      were used for the assimilation studies before the frost treatment. The same trees
      were then subjected to a second frost of -18 degrees C for three hours during the
      following night and the recovery of A(max) of the same branches was measured the
      next day. All of the acid mist treatments increased A(max) and apparent quantum
      yield relative to the control treatment when measured before the frost
      treatments. Frosts of -10 and -18 degrees C resulted in a significant decline in
      A(max) of seedlings in all treatments except the control. Stomatal conductance
      increased with increasing irradiance in seedlings in the acid mist treatments
      that did not contain SO(4) (2-) ion. Stomatal conductance of seedlings in acid
      mist treatments containing SO(4) (2-) ion was insensitive to changes in
      irradiance over the range 50-1500 micro mol m(-2) s(-1). It is concluded that
      acid precipitation increased the sensitivity of the assimilation response to
      midwinter frosts that follow a brief warm period. The SO(4) (2-) ion appears to
      be significant in causing increased sensitivity to frost and in causing stomatal
      insensitivity to light flux density.

PMID- 14969893
TI  - Analysis of the relationships among O(3) uptake, conductance, and photosynthesis
      in needles of Pinus ponderosa.
AB  - We studied the effects of O(3) uptake on conductance (g(wv)) and photosynthesis
      (A) in needles of ponderosa pine (Pinus ponderosa Laws.) seedlings exposed for 70
      days to one of three O(3) regimes-Low-O(3) (0.1 micro mol mol(-1) daily peak),
      High-O(3) (0.2 micro mol mol(-1) daily peak), and Low/High-O(3) (alternating 2
      days Low-O(3) and 2 days High-O(3)). Seedlings exposed to charcoal-filtered air
      served as controls. Total O(3) exposures, expressed as ppm-h (the sum of the
      average hourly concentration in ppm ( micro mol mol(-1)) over the exposure
      period), were 77, 135, 105 and 4 for the Low-O(3), High-O(3), Low/High-O(3) and
      control treatments, respectively. Conductance (g(wv)) declined to about 60% of
      the value in control seedlings by Day 6 in seedlings in the High-O(3) treatment
      and by Day 37 in seedlings in the Low/High-O(3) treatment, but g(wv) did not
      decline at all in seedlings in the Low-O(3) treatment. At the end of the 70-day
      experiment, cumulative O(3) uptake, calculated from measured g(wv) values and
      assuming an internal O(3) concentration of zero, was 12.2, 13.5, and 14.7 mmol m(
      2) for seedlings in the Low-O(3), Low/High-O(3), and High-O(3) treatments,
      respectively; however, O(3) uptake was reduced by 0, 24, and 36%, respectively,
      from that expected if there had been no decline in g(wv). With increasing total
      O(3) exposure, A declined, but the reduction was not strictly cumulative, i.e., A
      measured on Days 49 and 70 was similar for a given treatment even though both
      total O(3) exposure and uptake had increased. At the end of the experiment, A at
      near saturating CO(2) (1000 micro mol mol(-1)) and saturating photosynthetic
      photon flux density was reduced by about 25, 40 and 50% in seedlings in the Low
      O(3), Low/High-O(3) and High-O(3) treatments, respectively, compared to the
      control seedlings. The ratio of internal to external CO(2) concentrations, an
      indicator of relative change in stomatal limitation of A, did not change over
      time and did not differ among treatments, suggesting that A and g(wv) decreased
      in parallel. After 40-60 days without O(3), A of seedlings in all O(3) treatments
      was not significantly different. Our data indicate that O(3)-induced stomatal
      closure was a result of reduced A and that decreased g(wv) reduced O(3) uptake to
      a rate that needles of ponderosa pine could tolerate without exhibiting further
      reductions in gas exchange capacity.

PMID- 14969894
TI  - Growth and nutrition of nonmycorrhizal and mycorrhizal pitch pine (Pinus rigida)
      seedlings under phosphorus limitation.
AB  - The association of ectomycorrhizal fungi with tree roots enhances the acquisition
      of phosphorus (P) from the soil. In addition to increasing the uptake of
      H(2)PO(4) (-) (P(i)), mycorrhizal fungi may increase the spectrum of P sources
      utilized by tree roots by mediating the dissolution of insoluble metallophosphate
      salts or the hydrolysis of organic P compounds. To investigate the role of
      ectomycorrhizal fungi in enhancing P acquisition by tree roots, pitch pine (Pinus
      rigida Mill.) seedlings were grown in sand culture with or without the
      ectomycorrhizal symbiont Pisolithus tinctorius Coker and Couch under various
      conditions of P limitation. Compared with nonmycorrhizal seedlings, seedlings
      inoculated with P. tinctorius exhibited a greater capacity to function under P
      limitation as evidenced by superior growth and the maintenance of normal foliar
      ion composition at low P(i) concentrations. Nonmycorrhizal seedlings subjected to
      P-limiting conditions exhibited depressed K and P and elevated Na concentrations
      in foliage. The association of P. tinctorius with pitch pine seedling roots
      maintained foliar K concentrations and prevented the accumulation of Na under P
      limitation. Nonmycorrhizal seedlings were unable to obtain P from either solid
      AlPO(4) or inositol hexaphosphate (IHP), whereas seedlings inoculated with P.
      tinctorius utilized AlPO(4), but not IHP as a P source. Root surface acid
      phosphatase (APase) activity was depressed in roots infected with the mycorrhizal
      symbiont and was negatively correlated with seedling growth on all P sources.
      Root APase activity was negatively correlated with foliar P concentrations in
      seedlings grown on P(i), but was not correlated with foliar P concentrations in
      seedlings cultured with AlPO(4) or IHP.

PMID- 14969895
TI  - Growth and photosynthesis of tropical forest tree seedlings (Bischofia javanica
      Blume) as influenced by a change in light availability.
AB  - Acclimation in seedlings of Bischofia javanica Blume, which are commonly found in
      canopy gaps in the moist forests of tropical Asia, to a change in light
      availability was examined in a controlled environment simulating forest shade and
      daylight. Seedlings were grown in a high (1000 micro mol m(-2) s(-1); red/far
      red, 1.45) or low (40 micro mol m(-2) s(-1); red/far-red, 0.10) light regime and
      then transferred to the contrasting light environment for nine weeks. Control
      seedlings were maintained in the same light regime throughout the study. The
      availability of light influenced relative growth rate through morphological and
      physiological adjustments. Transferred seedlings retained the leaves that had
      been developed before transfer, and no leaf-shedding was observed till the end of
      the experiment. Leaves formed in the new light regime were physiologically and
      morphologically identical to those of the corresponding controls. High-light
      seedlings transferred to low light displayed significantly lower relative growth
      rate than the low-light controls because of a lower leaf area ratio carried over
      from the previous high-light environment. A reverse pattern of response with
      respect to relative growth rate was observed for the low-light seedlings
      transferred to high light compared to the high-light controls. The higher
      relative growth rate in the low-light seedlings transferred to high light was the
      result of higher net assimilation rate and higher leaf area ratio. The higher
      leaf area ratio in the low-light seedlings transferred to high light was the
      consequence of the effects of previous environment, and the relatively lower net
      assimilation rate in the high-light control seedlings was, at least partly, due
      to the effects of self-shading rather than to the photosynthetic capacity of the
      leaves. The results suggest that the species has a wide acclimation potential to
      a change in light availability that might occur in nature following gap creation
      or canopy closure.

PMID- 14969896
TI  - Three dimensional distribution of needle and stem surface area in a Douglas-fir.
AB  - The distribution of needles and branches in the crown of a 14-m tall Douglas-fir
      was investigated for the purpose of developing a three-dimensional structure for
      use with radiation transfer models. We found a linear relationship between the
      basal area of main branches originating at the bole and the total one-sided
      planimetric surface area of the foliage attached to each branch. A similar linear
      relationship was found between the branch basal area and the mass of stem
      material on the branch. Total silhouette area (needles plus branch material) did
      not vary significantly horizontally along the branch length, but stem surface
      area declined linearly from near the bole to the branch tip. Needle surface
      silhouette area and leaf area index increased along the main branch from near the
      bole to the branch tip. Silhouette leaf area (STAR) did not vary along the main
      branch. The needle area density (NAD) (m(2) m(-3)) was calculated for each of the
      lower 11 whorls; the vertical distribution of NAD increased from the base of the
      bole to the top of the crown.

PMID- 14969897
TI  - Seasonal and topographic patterns of forest floor CO(2) efflux from an upland oak
      forest.
AB  - Forest floor CO(2) efflux (FF(cer)) is an important component of global carbon
      budgets, but the spatial variability of forest floor respiration within a forest
      type is not well documented. Measurements of FF(cer) were initiated in mid-March
      of 1991 and continued at biweekly to monthly intervals until mid-November.
      Observations were made at 45 sites along topographic gradients of the Walker
      Branch Watershed, Tennessee including northeast and southwest facing slopes,
      valley-bottoms, and exposed ridge-top locations. The FF(cer) measurements were
      made with a portable gas-exchange system, and all observations were accompanied
      by soil temperature and soil water content measurements. As expected, FF(cer)
      exhibited a distinct seasonal trend following patterns of soil temperature, but
      soil water content and the volume percent of the soil's coarse fraction were also
      correlated with observed rates. Over the entire measurement period, FF(cer)
      ranged from a typical minimum of 0.8 micro mol m(-2) s(-1) to an average maximum
      near 5.7 micro mol m(-2) s(-1). No significant differences in FF(cer) were
      observed among the ridge-top and slope positions, but FF(cer) in the valley
      bottom locations was lower on several occasions. An empirical model of FF(cer)
      based on these observations is suggested for application to whole-stand estimates
      of forest carbon sequestration.

PMID- 14969898
TI  - Changes in photosynthesis and water status of developing leaves of Brachystegia
      spiciformis Benth.
AB  - Changes in net carbon assimilation and water status were studied during leaf
      development in the deciduous, tropical species Brachystegia spiciformis Benth. In
      this upland savanna African tree, bud-burst and leaf development occur
      approximately two months before the rainy season. The newly formed leaves
      synthesize anthocyanin until the fully expanded leaves of the whole canopy are
      red. This foliage is referred to as "spring flush" foliage. Subsequently, the
      anthocyanins are metabolized and the pre-rain leaves become green. Carbon dioxide
      assimilation exhibited a bimodal diurnal pattern and was similar for pre-rain
      green leaves and fully expanded flushing leaves, although pre-rain green leaves
      showed a net uptake of carbon throughout the daylight period, whereas flushing
      leaves exhibited only brief periods of net photosynthesis in the morning and
      early afternoon. Measurements of leaf water potential and relative water content
      showed a diurnal pattern with considerable variation throughout the day. Leaf
      water potential and relative water content values decreased soon after sunrise
      reaching a minimum at a time corresponding to the afternoon peak in CO(2)
      assimilation. Stomatal conductance was closely related to transpiration rate in
      both flushing and pre-rain green leaves, although flushing leaves had lower
      stomatal conductances than pre-rain green leaves. Pre-rain green leaves exhibited
      a compensation irradiance of approximately 180 micro mol m(-2) s(-1), whereas
      flushing leaves had positive net photosynthesis only at PPFDs greater than 300
      micro mol m(-2) s(-1). Rate of photosynthesis (expressed per leaf area or
      chlorophyll unit) increased as anthocyanin concentration decreased, although the
      photosynthetic rate continued to increase long after the leaf anthocyanins had
      been degraded to low, visually undetectable amounts. Post-rain green leaves had
      chlorophyll concentrations, transpiration rates and stomatal conductances similar
      to those of pre-rain green leaves; however, photosynthetic rates in post-rain
      leaves were more than three times higher. Thus, during the early stages of the
      spring flush, carbon asimilation rates of the flushing leaves were inversely
      related to leaf anthocyanin concentrations. In pre-rain green leaves,
      photosynthesis was limited by other non-stomatal factors.

PMID- 14969899
TI  - Simulated influence of leaf geometry on sunlight interception and photosynthesis
      in conifer needles.
AB  - The light interception capabilities of individual conifer needles are governed by
      their cross-sectional geometry and their orientation to sunlight. Leaf cross
      sections typical of conifer tree species were modeled to quantify the
      interception of direct sunlight over a range of incident light angles. The needle
      shapes exhibited by Abies nordmanniana Spach, Picea asperata Master, Pinus cembra
      L., P. monophylla Torr & Frem., and P. sylvestris L. were selected because they
      are representative of the range of geometric shapes found in conifer tree
      species. Calculated light interception values were compared to corresponding
      predictions for a laminar broadleaf. Estimates of carbon gain were derived from
      computed incident light integrated over the leaf cross section and a
      representative curve of conifer photosynthetic response to light. Flat leaf cross
      sections (e.g., Abies nordmanniana) with high surface area to volume ratios (> 6)
      intercepted more light per unit area at high angles of incidence than thick
      leaves. Thick leaves (e.g., Pinus cembra) intercepted more light at low angles of
      incidence than at high angles of incidence. Needles of Pinus monophylla had no
      angular dependence for light interception because of their circular cross
      section. Large differences in estimated CO(2) assimilation occurred among the
      species, especially when CO(2) uptake was expressed on a unit volume basis. A
      maximum uptake of 67.9 mmol CO(2) m(-3) s(-1) was predicted for A. nordmanniana
      compared to a minimum of 39.7 mmol m(-3) s(-1) for P. monophylla. A greater
      angular dependence occurred for estimates of CO(2) uptake than for estimates of
      light interception.

PMID- 14969900
TI  - Shoot dynamics of Pinus pumila in relation to altitudinal and wind exposure
      gradients on the Kiso mountain range, central Japan.
AB  - Seasonal shoot dynamics of Japanese mountain stone pine (Pinus pumila Regel.)
      growing at six sites with different altitudes and slope aspects on the Kiso
      mountain range in central Japan were investigated. The shoots followed a similar
      growth pattern at all sites; current shoots elongated rapidly during June and
      July, and the current needles grew during July and August. Final lengths of the
      current shoots and needles decreased with increasing altitude. Current-shoot
      lengths were also shorter at the windward sites than at the leeward sites. At all
      sites, leaf senescence occurred intensively between mid-August and mid-September.
      Needle longevity, i.e., the age of the oldest living needle attached to a shoot,
      increased with increasing altitude. Fascicle density, i.e., the number of current
      needle fascicles on a unit shoot length, was greater at higher altitudes and
      windward sites than at lower altitudes and leeward sites. Seasonal dynamics of
      the P. pumila shoots were characterized by simultaneous replacement of old
      needles with new needles in the early autumn, thus avoiding any loss of canopy
      photosynthetic production during the growing season. Increases in needle
      longevity and fascicle density were associated with declining air temperature and
      increasing wind exposure. Needle longevity and fascicle density were
      characteristics of adaptive plasticity in P. pumila that prevent a reduction in
      growth potential in the stressful conditions of alpine regions.

PMID- 14969901
TI  - Gas exchange characteristics of mangosteen (Garcinia mangostana L.) leaves.
AB  - Gas exchange responses of mangosteen (Garcinia mangostana L.) leaves to
      photosynthetic photon flux density (PPFD), internal CO(2) concentration (C(i)),
      leaf-air vapor pressure deficit (VPD), leaf temperature (T(l)) and time of day
      were investigated in plants grown in three shade treatments. Maximal
      photosynthetic rate (P(n(max))) per unit leaf area at light saturation did not
      differ significantly among plants grown in the different shade treatments despite
      significant morphological differences. Light compensation point (9-15 micro mol
      m(-2) s(-1)) and quantum yield (0.022-0.023) did not differ significantly among
      treatments, whereas light saturation point was significantly higher for leaves
      grown in 20% shade than for leaves grown in 50 or 80% shade (951, 645 and 555
      micro mol m(-2) s(-1), respectively). Shade treatments significantly affected
      assimilation responses to varying CO(2) concentrations. At CO(2) concentrations
      between 600 and 1000 micro mol mol(-1), leaves from the 20% shade treatment
      recorded higher P(n) (6.44 micro mol m(-2) s(-1)) than leaves from the 80% shade
      treatment (4.57 micro mol m(-2) s(-1)). Stomatal conductance (g(s)) decreased
      with increasing CO(2) concentrations. Vapor pressure deficits higher than 2.5 kPa
      significantly decreased P(n) and g(s), whereas P(n) remained steady over a 24-33
      degrees C temperature range in leaves in 80% shade and over a 27-36 degrees C
      range in leaves in 20 and 50% shade. Highest carbon gain during a 12-hour
      photoperiod was observed for leaves grown in 50% shade. The results imply that
      mangosteen is a shade-tolerant, lower canopy tree adapted to humid tropical
      lowlands. Providing low VPD in the nursery may result in maximal growth. However
      leaves of seedlings grown in 50 or 20% shade tolerated high VPD and temperatures
      better than leaves of seedlings grown in 80% shade, indicating some adaptability
      to the seasonally wet and dry tropics of northern Australia.

PMID- 14969902
TI  - Free amino acids and protein in Scots pine seedlings cultivated at different
      nutrient availabilities.
AB  - Scots pine (Pinus sylvestris L.) seedlings of a provenance from northern Sweden
      were cultivated hydroponically for 7 weeks in a climate chamber. The nutrient
      solution contained either 2.5 (low-N) or 50 (high-N) mg N l(-1) with other
      essential elements added in a fixed optimal proportion to the nitrogen. After 5
      and 7 weeks, the seedlings were analyzed for growth, total nitrogen and other
      essential nutrients, protein and free amino acids. Low-N seedlings grew more
      slowly and had higher root/shoot ratios than high-N seedlings. With respect to
      total nitrogen, the effect of the lower nutrient supply was mainly on the
      nitrogen content of the whole plant and the allocation of nitrogen among tissues,
      not on tissue nitrogen concentration. This was also the case for potassium,
      phosphorus, calcium and magnesium. The proportions by weight among these
      macronutrients in the whole seedlings were similar in both nutrient regimes. The
      proportion and concentration of sulfur were significantly lower in low-N
      seedlings than in high-N seedlings, because of a lower net uptake of sulfur than
      of other macronutrients. The shoot, needles and stem of low-N seedlings had
      higher concentrations of free amino acids and lower concentrations of protein
      than the shoot, needles and stem of high-N seedlings. Arginine dominated the pool
      of free amino acids in the low-N seedlings, whereas glutamine predominated in the
      high-N seedlings. We conclude that Scots pine seedlings accumulated soluble
      nitrogen as arginine when net protein synthesis was limited by factors other than
      nitrogen availability. Nutritional imbalance, as revealed by growth
      characteristics and a suboptimal proportion and concentration of sulfur in the
      seedlings, probably affected synthesis of S-amino acids, resulting in the
      diversion of assimilated nitrogen to arginine instead of protein.

PMID- 14969903
TI  - Needle polyamine concentrations and potassium nutrition in Scots pine.
AB  - The response of free polyamines (putrescine, spermidine and spermine) in needles
      of Scots pine (Pinus sylvestris L.) to varying needle potassium concentrations
      was investigated in two potassium fertilization experiments on drained peatlands.
      A significant negative correlation was observed between putrescine and potassium
      concentrations in needles. Putrescine responded more sensitively to decreasing
      needle K concentrations during the growing season than during the winter.
      Putrescine accumulation started when needle potassium concentrations were above
      5.5 mg g(dw) (-1) in summer and above 5.0 mg g(dw) (-1) in winter. A decrease in
      needle potassium concentrations below 4.3 mg g(dw) (-1) in summer and below 3.5
      mg g(dw) (-1) in winter resulted in an exponential increase in putrescine
      concentrations. Putrescine accumulation was initiated well above the needle
      potassium concentrations generally considered indicative of deficiency. The
      exponential increase in putrescine concentrations in winter occurred within the
      range of needle potassium concentrations that has been identified as indicating
      severe potassium deficiency.

PMID- 14969904
TI  - Cold acclimation of Pinus contorta and Pinus sylvestris assessed by chlorophyll
      fluorescence.
AB  - Needle samples of six provenances each of lodgepole pine (Pinus contorta Dougl.
      var. latifolia) and Scots pine (Pinus sylvestris L.), originating from latitudes
      55 to 68 degrees N in western Canada and northern Sweden, were collected during
      the autumn and subjected to freezing temperatures in the range of -8 to -29
      degrees C on three occasions in September and October. Needle injury was assessed
      by two different methods: visual assessment and chlorophyll a fluorescence.
      Chlorophyll a fluorescence data showed a highly significant correlation with the
      visual assessments of injury, indicating that the technique can be used as a
      simple, non-destructive and objective measure for rapid detection of freezing
      injury and for ranking of needle materials with respect to development of cold
      acclimation. The analyses showed that, during the autumn, lodgepole pine needles
      were more hardy and acclimated to low temperatures earlier than Scots pine
      needles.

PMID- 14969905
TI  - Canopy dynamics and aboveground production of five tree species with different
      leaf longevities.
AB  - Canopy dynamics and aboveground net primary production (ANPP) were studied in
      replicated monospecific and dual-species plantations comprised of species with
      different leaf longevities. In the monospecific plantations, leaf longevity
      averaged 5, 6, 36, 46 and 66 months for Quercus rubra L., Larix decidua Miller,
      Pinus strobus L., Pinus resinosa Ait. and Picea abies (L.) Karst., respectively.
      Specific leaf area, maximum net photosynthesis per unit mass (A/mass), leaf N per
      unit mass (N(leaf)/mass) and maximum net photosynthesis on a leaf N basis
      (A/N(leaf)) were inversely correlated to leaf longevity (r(2) = 0.92-0.97, 0.91,
      0.88 and 0.80, respectively). Maximum net photosynthesis per unit area (A/area)
      was not correlated to leaf longevity, whereas leaf N per unit area (N(leaf)/area)
      was positively correlated to leaf longevity (r(2) = 0.95). For a similar-diameter
      conifer, species with long-lived foliage supported a greater foliage mass than
      species with short-lived foliage; however, Quercus rubra did not follow this
      pattern. At the stand level, total foliage mass ranged from 3.3 to 30.5 Mg ha(-1)
      and was positively correlated (r(2) = 0.97) to leaf longevity. Leaf area index
      (LAI) was also positively correlated (r(2) = 0.82) to leaf longevity. Production
      efficiency (ANPP/LAI) was inversely related to leaf longevity and positively
      related to A/mass. Aboveground biomass and net primary production differed
      significantly (P < 0.05) among the five species but were not correlated to leaf
      longevity, total foliage mass or leaf area. In monospecific plantations, stem NPP
      for Larix decidua was 17% greater than for Pinus strobus and 14% less than for
      Picea abies, but in mixed-species plantations stem NPP for Larix decidua was 62
      and 85% greater than for Pinus strobus and Picea abies, respectively. Similar
      aboveground net primary production rates can be attained by tree species with
      different leaf longevities because of trade-offs resulting from different
      structural and physiological leaf and canopy characteristics that are correlated
      to each other and to leaf longevity.

PMID- 14969906
TI  - The relationship between crown size and ring width in Pinus sylvestris L. stems:
      dependence on indole-3-acetic acid, carbohydrates and nitrogen in the cambial
      region.
AB  - Indole-3-acetic acid (IAA), carbohydrates, total nitrogen and amino acids in the
      cambial region and bark were measured at the top (10-year-old internode) and
      bottom (1.3 m) of the main stem of 50-year-old Pinus sylvestris L. trees, having
      different rates and longitudinal gradients of annual ring width formation. The
      trees were sampled during the most active period of wood production (June 23,
      July 15) and at the end of this period (August 23). Trees with a small crown and
      relatively slow growth rate (S-trees) were compared with trees in the same stand
      that had a large crown and fast growth rate (F-trees) as a result of thinning and
      fertilization. The effect of bottom pruning fast-growing trees (pruned F-trees)
      was also investigated. The F-trees had greater wood production than the S-trees
      at both the stem top and bottom. The difference was larger at the stem bottom,
      thus the relative decrease in ring width down the stem was steeper in the S
      trees. The amount of sucrose and IAA per cm(2) in cambial region tissues was
      higher in F-trees than in S-trees. However, the differences in annual ring width
      between treatments and within trees were not reflected in the concentrations
      (expressed per gram fresh weight) of these substances, measured either in
      differentiating xylem, the cambium plus phloem, or in the cambial region as a
      whole. The concentrations of total nitrogen and amino acids were slightly higher
      in the F-trees than in the S-trees. Pruning the F-trees reduced wood production,
      particularly at the stem bottom, inhibited the springtime increase in starch, and
      decreased the amounts of sucrose and IAA per cm(2) in the cambial region.
      However, it was evident that the concentrations of sucrose, IAA, amino acid and
      nitrogen in the cambial region were not related to ring width. During June and
      July, the concentrations of these substances were generally higher at the stem
      bottom in the pruned F-trees than in the F-trees. The results provide evidence
      that it is the activity of the cambium rather than the availability of
      carbohydrates that determines the allocation of wood production along the tree
      stem. The results also indicate that tracheid production is not directly related
      to the IAA concentration in the cambial region.

PMID- 14969907
TI  - Maturation of maritime pine (Pinus pinaster Ait.) seedlings after exposure to a
      period of continuous light.
AB  - Nine half-sib families of maritime pine (Pinus pinaster Ait.) of known adult
      performance were grown in continuous light at either 25 degrees C or 25/20
      degrees C for 18 weeks. They were then exposed to a dormancy induction period
      followed by a dormancy release period and then grown for a further 9 weeks in a
      16-h photoperiod at a day/night temperature of 25/20 degrees C. Seedlings
      exhibited great diversity in morphology at the end of the first growth period.
      The number of morphogenetic cycles varied between one and three and the form of
      the apical meristem ranged from a typical rosette to an adult-like bud. The type
      of seedling obtained at the end of the first growth period strongly influenced
      later growth, independently of the temperature regime. Maturity was proportional
      to the number of morphogenetic cycles achieved during the first growth period and
      was characterized by short growth duration, small primary needles and a high
      degree of fixed growth. The state of the apical meristem that underwent the
      dormancy period had less influence on the rate of maturation than the number of
      morphogenetic cycles. The time course of maturation was endogenously controlled
      and varied among traits. Conspicuous morphological differences were not
      associated with changes in the relationship between growth components at the
      phenotypic level. However, there seemed to be a shift in the genetic correlations
      between growth components after first budset.

PMID- 14969908
TI  - The effect of Paxillus involutus Fr. on aluminum sensitivity of Norway spruce
      seedlings.
AB  - Non-mycorrhizal Norway spruce seedlings (Picea abies Karst.) and Norway spruce
      seedlings colonized with Paxillus involutus Fr. were grown in an axenic silica
      sand culture system. After successful mycorrhizal colonization, the seedlings
      were exposed to 200 or 800 micro M AlCl(3) for 10 weeks. In both non-mycorrhizal
      and mycorrhizal seedlings, exposure to Al significantly reduced root growth and
      the uptake of Mg and Ca. After 5 weeks of exposure to 800 micro M Al, the
      mycorrhizal seedlings had significantly higher chlorophyll concentrations than
      the non-mycorrhizal seedlings, although no difference in Mg nutrition was
      apparent. After 10 weeks of exposure to Al, both non-mycorrhizal and mycorrhizal
      seedlings exhibited needle chlorosis and reduced photosynthetic activity.
      However, the aluminum-induced reduction in shoot growth was largely ameliorated
      by colonization with P. involutus. We conclude that mycorrhizal colonization
      modifies the phytotoxic effects of Al in Norway spruce seedlings. However,
      differences in physiological responses to Al between mycorrhizal and non
      mycorrhizal seedlings may be largely reduced in the long term as a result of
      impaired mineral nutrient uptake.

PMID- 14969909
TI  - Physiological adjustment of two full-sib families of ponderosa pine to elevated
      CO(2).
AB  - Seeds from two full-sib families of ponderosa pine (Pinus ponderosa) with known
      differences in growth rates were germinated and grown in an ambient (350 micro l
      l(-1)) or elevated (700 micro l l(-1)) CO(2) concentration. Gas exchange at both
      ambient and elevated CO(2) concentrations was measured 1, 6, 39, and 112 days
      after the seed coat was shed. Initial stimulation of CO(2) exchange rate (CER) by
      elevated CO(2) was large (> 100%). On Day 1, CER of seedlings grown in elevated
      CO(2) and measured at ambient CO(2) was significantly lower than the CER of
      seedlings grown and measured at ambient CO(2), indicating physiological
      adjustment of the seedlings exposed to elevated CO(2). Physiological acclimation
      to elevated CO(2) was complete by Day 39 when there was no significant difference
      in CER between seedlings grown and measured at ambient CO(2) and seedlings grown
      and measured at elevated CO(2). After 4 months, the light response of seedlings
      in the two treatments was determined at both ambient and elevated CO(2). Light
      compensation point, CER at light saturation, and apparent quantum efficiency of
      seedlings grown and measured at ambient CO(2) were not significantly different
      from those of seedlings grown and measured at elevated CO(2). With a short-term
      increase in CO(2), CER at light saturation (5.16 +/- 0.52 versus 3.13 +/- 0.30
      micro mol CO(2) m(-2) s(-1)) and apparent quantum efficiency (0.082 +/- 0.011
      versus 0.045 +/- 0.003 micro mol CO(2) micro mol(-1) quanta) were significantly
      increased. Leaf C/N ratio was significantly increased in the elevated CO(2)
      treatment. There were few significant differences between families for any
      response to elevated CO(2). Under the experimental conditions, high growth rate
      was not correlated with a greater response to elevated CO(2).

PMID- 14969910
TI  - Effects of foliar nitrogen concentration on photosynthesis and water use
      efficiency in Douglas-fir.
AB  - Leaf-level physiological processes were studied in Douglas-fir (Pseudotsuga
      menziesii (Mirb.) Franco) to determine whether apparent increases in stand-level
      water use efficiency (WUE) observed in response to nitrogen (N) fertilization
      were attributable to foliar N effects on carbon fixation rates or on stomatal
      control of water loss. Photosynthesis and transpiration were measured at
      different light intensities and ambient CO(2) molar fractions and comparisons
      were made between current-year shoots with average foliar N concentrations of
      1.58% (High-N) and 1.25% (Low-N). Photosynthetic rates and foliar N
      concentrations were positively correlated. In response to light, photosynthesis
      and stomatal conductance were closely coupled and a similar coupling was observed
      in response to different ambient CO(2) concentrations. Partitioning the
      photosynthetic responses into mesophyll and stomatal components indicated that
      foliar N altered mesophyll conductance but not stomatal control of water loss.
      High-N shoots had significantly greater rates of photosynthesis and transpiration
      than Low-N shoots and, as a result, instantaneous WUE did not differ
      significantly between High-N and Low-N shoots.

PMID- 14969911
TI  - Agrobacterium rhizogenes-mediated transformation to improve rooting ability of
      eucalypts.
AB  - In an attempt to improve rooting in in vitro propagated Eucalyptus clones, root
      inducing genes on the Ri plasmids of three Agrobacterium rhizogenes strains were
      inserted into the Eucalyptus genome. Root development was monitored in vitro and
      after the plantlets had hardened off. Only transformed roots grew as root
      cultures in hormone-free liquid medium. The potential use of this procedure for
      improving rooting of clonal material is discussed.

PMID- 14969912
TI  - Restriction map and polymorphisms of nuclear ribosomal genes of Populus
      balsamifera.
AB  - Balsam poplar (Populus balsamifera) clones from five populations, which were
      collected along a transect from northern Wisconsin to the northern tree line,
      were evaluated for polymorphisms in nuclear ribosomal DNA. For this purpose, a
      restriction map was constructed using four six-cutter enzymes in single and
      double digests of genomic DNA. After electrophoretic separation on agarose gels
      and Southern transfer, blots were hybridized to non-radioactively labeled
      heterologous rDNA probes of soybean. Among populations, variation was detected in
      the length of the intergenic spacer between the tandem repeats of the coding
      regions and in the degree of methylation of one restriction enzyme recognition
      site. Based on a comparison of the derived restriction map of balsam poplar and
      other poplars, high homology was evident in the rDNA coding regions among
      species, whereas the intergenic spacer varied slightly in both length and number
      of restriction sites.

PMID- 14969913
TI  - A comparison of red spruce and balsam fir shoot structures.
AB  - I compared the shoot structures of high-elevation red spruce (Picea rubens Sarg.)
      and balsam fir (Abies balsamea (L.) Mill.). Needle widths, thicknesses and
      perimeters were measured to estimate total leaf areas from measured projected
      leaf areas. Measured needle perimeter/needle width ratios differed significantly
      from estimated ratios that assumed needles were either rhomboidal or elliptical
      in cross section. The vertical and horizontal silhouette shoot area to total leaf
      area ratios (STAR(v) and STAR(h)) of the two species were negatively correlated
      with needle packing and canopy height. Red spruce had higher values of STAR(v)
      than balsam fir at each canopy height, but STAR(v) declined with canopy height at
      a similar rate in the two species. The STAR(h) values of the two species did not
      differ significantly at a given canopy height. Needle packing increased with
      canopy height at the same rate in the two species. Needle weight increased in red
      spruce and decreased in balsam fir with increased needle packing, but showed no
      significant dependence on canopy height. Red spruce had higher values of STAR(h)
      than balsam fir at low values of needle packing, but STAR(h) values converged at
      high values of needle packing. The generally comparable values of STAR, along
      with similar needle diameters, may imply that red spruce and balsam fir have
      similar collection efficiencies of wet and dry particles. Measurements of STAR
      may be used to estimate leaf area indices (LAI) more accurately when using
      indirect techniques.

PMID- 14969914
TI  - Hydraulic resistance in Acer saccharum shoots and its influence on leaf water
      potential and transpiration.
AB  - A new method is presented for measuring whole-shoot hydraulic conductance, K(T)
      (kg s(-1) MPa(-1)). The method was also used to determine other conductance
      values in maple (Acer saccharum Marsh.) stem segments of differing diameter
      including: K(h) (absolute conductance or conductance per unit pressure gradient,
      kg s(-1) m MPa(-1)), K(s) (specific conductance or K(h) per unit wood area, kg s(
      1) m(-1) MPa(-1)), and LSC (leaf specific conductance or K(h) per unit leaf area,
      kg s(-1) m(-1) MPa(-1)). A regression of K(T) versus stem basal diameter, D (m),
      gave K(T) = 5.998 x 10(-2) D(1.402) (R(2) = 0.986 for D from 0.001 to 0.1 m) and
      a regression for leaf area, A(L) (m(2)), gave A(L) = 4.667 x 10(3) D(2.007) (R(2)
      = 0.981 for D from 0.001 to 0.3 m). More than 50% of the resistance to water flow
      in large shoots (0.1 m in diameter and 8 to 10 m long) was contained in branches
      less than 0.012 m in diameter, i.e., in the distal 1.5 m of branches. We used the
      regressions to predict the steady state difference in pressure potential, P,
      between the base of a shoot of diameter D and the average pressure potential at
      the apices of the shoot; the relation is given by P = 7.781 x 10(4) E D(0.605),
      where E is the average evaporative flux density (kg s(-1) m(-2)) in the leaves
      attached to the shoot. After comparing the predictions of this equation to field
      observations of E and leaf water potential and stomatal conductance, we concluded
      that the hydraulic conductance of large maple shoots is sufficiently low to
      prevent maximum stomatal conductance in maple leaves.

PMID- 14969915
TI  - Vascular cambial sucrose metabolism and growth in loblolly pine (Pinus taeda L.)
      in relation to transplanting stress.
AB  - Sucrose synthase (SS) was the dominant enzyme of sucrose metabolism in both stem
      and root vascular cambial zone tissues of nursery-grown loblolly pine (Pinus
      taeda L.) seedlings. Acid invertase (AI) and neutral invertase (NT) activities
      were generally less than 10% of the SS activity in both tissues. In both cambial
      tissues, seasonal patterns of enzyme activity were observed for SS but not for AI
      or NI. The seasonal patterns of SS activity in stem and root cambia paralleled
      the periodic growth of stems and roots. Stems had high SS activity and growth
      during summer and early fall. Roots had substantial SS activity and growth during
      summer and fall, but SS activity and growth were even higher in winter. When
      seedlings were transplanted, about eight months elapsed before stem and root
      cambia resumed rates of growth and sucrose metabolism similar to those in control
      nontransplanted seedlings. Two months after transplanting, root SS was at its
      lowest, whereas AI activity in transplants was 50% higher than in control
      nontransplanted seedlings. In stems, SS activity decreased in response to
      transplanting, whereas AI and NI activities did not change appreciably. In
      loblolly pine tissues, SS was specific for uridylates, whereas the nucleotide
      triphosphate-dependent phosphofructokinase (NTP-PFK) had similar activity with
      either UTP or ATP. Except in winter, the NTP-PFK was less active than the
      pyrophosphate-dependent phosphofructokinase (PPi-PFK) during all seasons. The PPi
      dependent PFK activity in nontransplanted seedlings followed similar seasonal and
      spatial patterns to those of SS activity. In actively growing tissues, such as
      stem cambial tissues in summer and root cambial tissues in winter, the measured
      total PFK to SS ratio ranged between 1.5/1 and 3/1. In contrast, in less actively
      growing tissues or transplanted seedlings, a greater decrease occurred in SS than
      in PFK activity, hence the ratio rose to as high as 12/1. It was concluded that:
      (1) SS was the dominant enzyme for sucrose metabolism in root and stem cambial
      tissues of loblolly pine seedlings; (2) both SS and PPi-PFK in the cambial
      tissues can be used as biochemical indicators of growth sink strength in stems
      and roots; and (3) both enzymes can be used as indicators of seedling stress
      caused by events such as transplanting and winter freezing.

PMID- 14969916
TI  - Carbon and nitrogen assimilation in red oaks (Quercus rubra L.) subject to
      defoliation and nitrogen stress.
AB  - To examine how rates of net photosynthesis and N uptake of red oak seedlings
      respond to defoliation under contrasting conditions of N availability, nitrogen
      deficient plants were grown in sand culture and subjected to partial defoliation
      and increased N availability under low light conditions. Both photosynthesis and
      N uptake rates were measured regularly before and after the treatments.
      Defoliation resulted in elevated rates of net photosynthesis in both low-N and
      high-N trees, but the high-N trees were able to maintain the high photosynthetic
      rates for a longer period of time. Nitrogen availability did not affect the
      photosynthetic rate of the undefoliated plants. Nitrogen uptake was not affected
      by the defoliation treatment, but was increased by increasing N availability in
      both the defoliated and undefoliated plants. Nitrogen uptake rates increased less
      than would be expected on the basis of N availability alone, but the uptake rates
      were apparently not limited by carbon supply in the short term. Suboptimal
      concentrations of N in plant tissues resulted in a strong sink for N even in the
      absence of refoliation.

PMID- 14969917
TI  - Ecophysiology of shade needles of Picea glauca saplings in relation to removal of
      competing hardwoods and degree of prior shading.
AB  - We studied shade needles of Picea glauca (Moench) Voss saplings that were growing
      in 15, 45 or 90% shade from competing vegetation at northern boreal forest sites
      in Alberta and Saskatchewan. At each site, in late May or early June 1990, all
      hardwoods were removed within a 2-m radius of each of eight saplings in each
      shade treatment (released saplings), and eight saplings in each shade treatment
      were left as controls. Light-saturated net assimilation (NA), stomatal and
      mesophyll conductance and water use efficiency of one-year-old needles were
      measured four times during the 1990 growing season and in the spring of 1991.
      There was a trend of increased photosynthetic capacity within one week following
      release. By August 1990 and in the following spring, NA was higher in released
      trees than in controls. The increase in NA appeared to be related to increased
      stomatal conductance to water vapor and to increased foliar nitrogen and
      resulting increases in mesophyll conductance to CO(2). There was no measurable
      effect of degree of shading prior to release on NA following release. Foliage of
      the released saplings appeared capable of rapid acclimation to the open
      conditions.

PMID- 14969918
TI  - Rapid response of large, drought-stressed beech trees to irrigation.
AB  - Large, declining beech (Fagus sylvatica L.) trees (diameter at breast height = 50
      cm), growing on heavy clay soils in the highlands near Zurich, Switzerland, were
      amply irrigated in late summer. During irrigation, the xylem sap flow rate,
      Q(wt), was measured by the stem-tissue heat balance method with internal heating
      and sensing. Only a gradual and slight increase in Q(wt) in response to
      irrigation was observed in the control trees, whereas Q(wt) in the declining
      trees, whose transpiration rates were only 2-20% those of the control trees,
      increased 2-5 times within minutes. This suggests, that severe local drought was
      the major factor limiting tree growth at the site. The extent of the response
      permits estimation of the supply-limited (soil water) and demand-limited (tree
      structure) components of stress. Drought caused a decline in Q(wt) in the trees
      with short crowns and limited root systems that had originally been growing in
      dense canopies and had become suddenly exposed to full illumination as a result
      of a severe wind storm and thinning. Trees with deep, narrow, dense crowns,
      growing in more open places and adapted over a long period to high irradiance
      remained healthy during drought. Prolonged, periodic water shortage reduced the
      amount of foliage up to 90% but during drought stimulated the growth of fine
      roots in the surface and upper soil layers. The stem conductive systems of the
      declining trees were still partially functional.

PMID- 14969919
TI  - Growth and mineral nutrition of Gmelina arborea Roxb. seedlings fertilized with
      four sources of nitrogen on a latosolic soil.
AB  - The growth and mineral nutrition of Gmelina arborea Roxb. seedlings were
      investigated in response to four nitrogen-based fertilizers applied at 0, 2.5,
      5.0 or 7.5 g N per plant. Nitrogen sources included NH(4)-N as ammonium sulfate,
      NO(3)-N as potassium nitrate, NH(4)NO(3)-N as calcium ammonium nitrate, and urea
      N as urea. Seedlings fertilized with NH(4)NO(3)-N or urea-N had greater height,
      collar diameter, dry weight, net assimilation rate, and relative growth rate than
      seedlings fertilized with NH(4)-N or NO(3)-N. For all sources of nitrogen,
      increasing the amount of exogenously supplied N per plant promoted shoot growth
      more than root development, hence the root to shoot ratios of all fertilized
      seedlings were smaller than those of the unfertilized controls. Applications of
      NO(3)-N increased the nitrogen, potassium, and phosphorus concentrations of
      fertilized seedlings. Regardless of source, a nitrogen application of 2.5 g N per
      plant was apparently optimal for the growth of Gmelina seedlings on a latosolic
      soil.

PMID- 14969920
TI  - Effects of thermal wounding, shading and exogenous auxin on some sprouting
      responses of coast redwood seedlings.
AB  - The effects of wounding, shading, and indole-3-acetic acid (IAA) on sprouting
      responses were examined in coast redwood (Sequoia sempervirens D. Don (Endl))
      seedlings. In August, two-year-old seedlings were given one of three thermal
      wounding treatments made with a blowtorch at the stem base. After 8 months, the
      heat-wounded seedlings were decapitated above the burl and IAA (0.00% to 1.00% by
      weight in lanolin) was applied to the cut surface every week for 8 weeks.
      Throughout the 8-week hormone treatment, the decapitated seedlings were subjected
      to one of three shading treatments (no shade, 70% shading and complete darkness).
      At the beginning of June, sprouts were harvested from each stump and measurements
      made of the length of the tallest sprout, number of sprouts, dry weight of all
      sprouts, and mean dry weight per sprout. All sprouting parameters showed negative
      responses to IAA. Shading decreased sprout number and sprout dry weight. Wounding
      increased maximum sprout length and dry weight per sprout but decreased the
      number of sprouts. Only the 2-way interaction between IAA and wounding was not
      significant for any of the responses.

PMID- 14969921
TI  - Variations in leaf morphometry and nitrogen concentration in Betula pendula
      Roth., Corylus avellana L. and Lonicera xylosteum L.
AB  - Relations between leaf dry weight to leaf area (LWA), leaf nitrogen concentration
      and irradiance inside a natural canopy were studied in Betula pendula Roth.,
      Corylus avellana L. and Lonicera xylosteum L. In all species, LWA increased with
      increasing irradiance. Relative variability in LWA was smaller in Betula pendula
      than in the other two species. In Corylus avellana, LWA also depended on total
      plant height. Foliar nitrogen concentration (on a dry weight basis) increased
      with increasing irradiance and LWA in Betula pendula, but decreased in the other
      two species. The interspecific variation in response to light availability and in
      nitrogen partitioning may be caused by different light demands or different life
      forms (trees versus shrubs), or both, of the species examined, and must be
      considered in contemporary canopy models.

PMID- 14969922
TI  - In vitro shoot proliferation determined by explant orientation of juvenile and
      mature Quercus rubra L.
AB  - Shoot cultures of Quercus rubra (L.) were established from both juvenile and
      adult plant material. Initial explants from epicormic shoots formed on the basal
      zone of the trunks had a greater capacity for in vitro establishment than
      explants from crown branches. The growth of vigorous axillary shoots was obtained
      by culturing decapitated shoots horizontally on Woody Plant Medium supplemented
      with 0.2 mg l(-1) of 6-benzylaminopurine. After 3 weeks of culture the shoots
      were transferred to fresh medium for two more weeks, giving a 5-week
      multiplication cycle. Efficient shoot production was achieved by combining three
      treatments favoring the growth of lateral buds: excision of the apex, horizontal
      culture and cytokinin treatment. The addition of indoleacetic acid or
      indolebutyric acid to the multiplication medium did not improve shoot
      proliferation rates, and naphthaleneacetic acid was detrimental. Recycling the
      same explant for several successive subcultures improved the efficiency of the
      propagation procedure. Using the optimal multiplication procedures, nine clones
      (six of juvenile origin and three from adult trees) were tested in vitro and it
      was found that genotype and age affected performance.

PMID- 14969923
TI  - A model analysis of the influence of root and foliage allocation on forest
      production and competition between trees.
AB  - A general model was constructed relating forest growth to nitrogen uptake and the
      partitioning of biomass among leaves, fine roots and woody tissues. The model was
      used to assess the influence of the allocation pattern on stand wood production,
      individual tree growth and nutrient cycling for even-aged conifer stands with
      adequate water, but suboptimal nitrogen. Stand wood production was maximized by
      quite low allocation to roots for specified amounts of plant-available nitrogen.
      However, the wood production of the individual was maximized by higher allocation
      to roots, because large root systems enhanced the ability of individuals to
      compete for nutrients. The optimal fine root allocation for a competing
      individual was less than 5% of total production for adequate nitrogen, but rose
      to 30% as nitrogen became more limiting, in general agreement with observed
      allocation patterns for fertilized versus non-fertilized forests. The high
      allocation to roots predicted for competitors may also enhance long-term
      productivity by decreasing nutrient losses from the ecosystem. Although
      collective, short-term stand wood production could be increased by shifting
      growth from roots to stems, this strategy may increase nutrient losses,
      ultimately decreasing productivity.

PMID- 14969924
TI  - Canopy development and solar conversion efficiency in Acacia auriculiformis under
      drought stress.
AB  - A glasshouse experiment was performed with Acacia auriculiformis seedlings to
      investigate the effects of decreased soil water potential on phyllode extension,
      abscission and solar conversion efficiency, e. Six-month-old seedlings were
      subjected for 39 days to one of four treatments: well watered (soil water
      potential maintained above -0.5 MPa), moderately drought stressed (soil water
      potential maintained above -1.5 MPa), severely drought stressed (soil water
      potential maintained above -2.5 MPa) and well watered but pruned to maintain a
      leaf area approximating that of the severely drought-stressed treatment.
      Aboveground biomass accumulation decreased by 21% below that of the well-watered
      controls in the moderately drought-stressed seedlings and by 47% in the severely
      drought-stressed seedlings as a result of both decreased interception of solar
      radiation and lower e. Differences in phyllode extension rate, rather than in
      phyllode abscission, were primarily responsible for the differences in
      interception of solar radiation among treatments. Decreases in phyllode extension
      rate and water use occurred simultaneously in response to decreasing soil water
      potential. Specific leaf area decreased and water use efficiency increased in
      response to drought stress.

PMID- 14969925
TI  - The effects of ultraviolet-B radiation on photosynthesis of different aged
      needles in field-grown loblolly pine.
AB  - We examined the effect of supplemental UV-B radiation (290-320 nm) on
      photosynthetic characteristics of different aged needles of 3-year-old, field
      grown loblolly pine (Pinus taeda L.). Needles in four age classes were examined:
      I, most recently fully expanded, year 3; II, first flush, year 3; III, final
      flush, year 2; and IV, oldest needles still present, year 2. Enhanced UV-B
      radiation caused a statistically significant decrease (6%) in the ratio of
      variable to maximum fluorescence (F(v)/F(m)) following dark adaptation only in
      needles from the youngest age class, suggesting transient damage to
      photosynthesis. However, no effects of enhanced UV-B radiation on other
      instantaneous measures of photosynthesis, including maximum photosynthesis,
      apparent quantum yield and dark respiration, were seen for needles of any age.
      Foliar nitrogen concentration was unaffected by UV-B treatment. However, the
      (13)C/(12)C carbon isotope ratios (delta(13)C-a time integrated measure of
      photosynthetic function) of needles in age classes II and IV were 3% (P < 0.01)
      and 2% (P < 0.05) more negative, respectively, in treated plants than in control
      plants. Exposure to enhanced UV-B radiation caused a 20% decrease in total
      biomass and a 4% (P < 0.05), 25% (P < 0.01), and 9% (P < 0.01) decrease in needle
      length of needles in age classes I, II, and IV, respectively. The observed
      decreases in delta(13)C, and F(v)/F(m) of the needles in the youngest needle age
      class suggest subtle damage to photosynthesis, although overall growth reductions
      were probably a result of decreased total leaf surface rather than decreased
      photosynthetic capacity. Needles of age class IV had lower light- and CO(2)
      saturated maximum photosynthetic rates (39%), lower dark respiration (34%), lower
      light saturation points (37%), lower foliar nitrogen concentration (28%), and
      lower delta(13)C (14%) values than needles of age class I. Apparent quantum yield
      and F(v)/F(m) did not change with needle age. The observed changes in
      photosynthesis and foliage chemical composition with needle age are consistent
      with previous studies of coniferous trees and may represent adaptations of older
      needles to shaded conditions within the canopy.

PMID- 14969926
TI  - The effects of acid rain and ozone on biomass and leaf area parameters of
      shortleaf pine (Pinus echinata Mill.).
AB  - Shortleaf pine (Pinus echinata Mill.) seedlings in 24 open-top chambers were
      exposed to combinations of ozone (carbon-filtered (control), ambient, 1.7 x
      ambient, and 2.5 x ambient) and acidic precipitation (pH 5.3, 4.3 and 3.3) for 16
      months (1989 harvest) or 28 months (1990 harvest). Although the effects of acid
      rain were generally not significant, there was a trend toward increased
      aboveground biomass and leaf area in seedlings subjected to the low pH
      treatments. Because N concentrations in the soils generally increased with
      decreasing pH, we concluded that the effects of acid rain on aboveground biomass
      and leaf area were a consequence of an increasing concentration of soil N. In the
      1989 harvest, seedlings in the 2.5 x ambient ozone treatment had significantly
      less biomass in all aboveground plant components and significantly less total
      leaf area than seedlings in the 1.7 x ambient ozone treatment. In the 1990
      harvest, there were no significant effects of ozone on total aboveground biomass,
      although there was a trend toward reduced biomass in seedlings in the 2.5 x
      ambient ozone treatment. Both total leaf area and leaf biomass were significantly
      less in seedlings exposed to 2.5 x ambient ozone for 28 months than in both
      control seedlings and seedlings in the 1.7 x ambient ozone treatment. The
      greater, but not always significant, aboveground biomass and leaf area of
      seedlings in the 1.7 x ambient ozone treatment compared with control seedlings
      may be associated with the observed increase in soil nitrate concentration as a
      result of increased rates of leaf senescence and litterfall.

PMID- 14969927
TI  - Planting stress, water status and non-structural carbohydrate concentrations in
      Corsican pine seedlings.
AB  - Two-year-old Corsican pine (Pinus nigra ssp. laricio var. Corsicana) seedlings
      were either well watered or subjected to a moderate drought for one month before
      being lifted from the nursery bed on October 9 and transplanted. Well-watered,
      non-transplanted seedlings served as controls. Needle predawn water potential
      (Psi(wp)), non-structural carbohydrate concentrations and plant development
      (survival, bud break, shoot elongation) were assessed before and during the first
      growing season after transplanting. On April 16, just before bud break, Psi(wp)
      was lower for the well-watered + transplanted and drought-conditioned +
      transplanted seedlings (Psi(wp) = -1.45 and -1.83 MPa, respectively) than for the
      controls (Psi(wp) = -0.56). There was a close relationship between the Psi(wp)
      measured on April 16 and bud break, shoot elongation and plant survival during
      the following growing period. Above a Psi(wp) of -1.1 MPa, all plants developed
      normally. Between -1.1 MPa and -1.6 MPa, bud break, and thus shoot elongation,
      did not occur in all plants. Between -1.6 MPa and -2.1 MPa, the plants were
      characterized by the absence of shoot growth, but mortality was zero. Below -2.1
      MPa, there was a large increase in plant mortality. On April 16, starch
      concentrations were markedly lower in the roots of transplanted seedlings than in
      the controls. There was a positive correlation between Psi(wp) and root starch
      concentration. The Psi(wp) (-2.3 MPa) at which complete starch depletion was
      observed in the roots corresponded to the Psi(wp) below which plants did not
      survive. These results suggest that mechanisms specifically linked to altered
      water status and metabolic processes associated with altered carbohydrate status
      are involved in transplanting stress; however, it was not possible to disentangle
      the two effects. Drought conditioning did not lead to a marked increase in
      soluble carbohydrate concentrations, as reported for other species, and did not
      increase plant tolerance to transplanting stress.

PMID- 14969928
TI  - Effect of photon flux density on carbon assimilation and chlorophyll a
      fluorescence of cold-stored white spruce and lodgepole pine seedlings.
AB  - White spruce (Picea glauca (Moench.) Voss) and lodgepole pine (Pinus contorta
      Dougl. var. latifolia Engelm.) seedlings previously held in dark, frozen storage
      (-2 degrees C) for 2.5 or 6 months, and nursery-grown white spruce seedlings
      lifted in summer were exposed to photon flux densities (PFDs) similar to those
      that might be encountered at planting. Photosynthetic gas exchange and
      chlorophyll a (chl a) fluorescence were examined in cold-stored and summer-lifted
      seedlings before and after a 9 h-exposure to artificial illumination of high PFD
      (2000 micro mol m(-2) s(-1)) or low PFD (ca. 500 micro mol m(-2) s(-1)), and
      during exposure to 400 micro mol m(-2) s(-1) for 4-9 days. In the 2.5-month
      stored and summer-lifted seedlings, the high-PFD treatment caused a small
      decrease in carbon fixation and a large decrease in the ratio of variable to
      maximum fluorescence (F(v)/F(m)) relative to the effect of the low-PFD treatment.
      In contrast, in the 6-month-stored seedlings the high-PFD treatment caused a
      significant decrease in rate of light-saturated carbon fixation but little
      decrease in F(v)/F(m) relative to the effect of the low-PFD treatment, indicating
      that the mechanisms for maintaining integrity of the photochemical apparatus had
      changed during the storage interval.

PMID- 14969929
TI  - Salinity and citriculture.
AB  - Soil salinity significantly limits citrus production in many areas worldwide.
      Although data on fruit yields in response to salinity are limited, they indicate
      that grapefruit, lemons, and oranges are among the most sensitive of all
      agricultural crops. Fruit yields decrease about 13% for each 1.0 dS m(-1)
      increase in electrical conductivity of the saturated-soil extract (EC(e)) once
      soil salinity exceeds a threshold EC(e) of 1.4 dS m(-1). Accumulation of excess
      Cl(-) and Na(+) can cause specific ion toxicities, but this problem can be
      minimized by selecting rootstocks that restrict the uptake of these ions. During
      the past two decades, numerous papers describing the agronomic and physiological
      responses of citrus to salinity have been published. This paper reviews these
      research reports and discusses differences in the response of citrus species to
      salt stress, the role of different rootstocks, the causes of salt injury, and the
      interactions of other environmental conditions or stresses with salinity.

PMID- 14969930
TI  - Sulfate concentrations in Norway spruce needles in relation to atmospheric SO(2):
      a comparison of trees from various forests in Germany with trees fumigated with
      SO(2) in growth chambers.
AB  - Concentrations of inorganic sulfur, organic sulfur and water-soluble cations and
      anions were determined in needles of young Norway spruce trees (Picea abies L.
      (Karst.)) that had been fumigated in growth chambers for weeks or months with
      different concentrations of SO(2), SO(2) plus ozone, or SO(2) plus NO(2).
      Measurements were also made on needles from older trees growing in forests in
      various regions of Germany with different mean annual atmospheric SO(2)
      emissions. In the fumigated young trees, sulfate accumulation in the needles was
      a linear function of atmospheric SO(2) concentration. Little or no sulfur was
      incorporated into the organic sulfur fraction. The mean accumulation rate of
      sulfate in needles of fumigated trees was about 0.4 nmol g(dw) (-1) (nl l(-1))(
      1) h(-1), which is very similar to the estimated rate of uptake of atmospheric
      SO(2) calculated from mean stomatal conductances (15 mmol m(-2) s(-1)) and the
      external SO(2) concentration (the calculated rate of uptake was 0.37 nmol g(dw) (
      1) (nl l(-1))(-1) h(-1)). Concentrations of organic acids and other inorganic
      ions did not change much in response to SO(2) fumigation. In needles collected
      from trees in south and southeast Germany, large differences in sulfate
      concentrations were observed that probably reflect SO(2) emissions in the
      different regions. The highest foliar sulfate concentrations, and the highest
      annual increase in sulfate concentration with needle age were observed in
      material collected from the heavily polluted Erzgebirge (up to 12 micro mol g(dw)
      (-1) year(-1)), followed by material from the Fichtelgebirge (up to 6 micro mol
      g(dw) (-1) year(-1)). If it is assumed that this annual increase is the result of
      uptake of SO(2) from the atmosphere, mean annual atmospheric SO(2) concentrations
      can be calculated. The calculated values were somewhat below the measured values
      in the Fichtelgebirge and in the heavily polluted Erzgebirge. Norway spruce trees
      can cope with high concentrations of atmospheric SO(2), provided that they can
      neutralize the sulfuric acid formed from SO(2). It appears that, in the field,
      the acid load is decreased by H(+) translocation to the roots and subsequent
      H(+)/K(+) exchange. However, this may be a very slow process, because it was not
      observed in the short-term fumigation experiments.

PMID- 14969931
TI  - Neutralization and buffering capacity of leaves of sugar maple, largetooth aspen,
      paper birch and balsam fir.
AB  - We compared the acidity, the external acid neutralizing capacity and the
      buffering capacity of leaves of four commercially important tree species,
      largetooth aspen (Populus grandidentata Michx.), sugar maple (Acer saccharum
      Marsh.), paper birch (Betula papyrifera Marsh.) and balsam fir (Abies balsamea
      (L.) Mill), at two sites of contrasting soil fertility in southern Quebec.
      External acid neutralizing capacity (ENC) of leaves was determined by measuring
      the change in pH induced by soaking fresh leaves in an acidic solution (pH 4.0)
      for two hours. The ENC was highest for largetooth aspen (14.3 micro equiv H(+) g(
      1)), and lowest for sugar maple and balsam fir (< 5 micro equiv H(+) g(-1)). The
      buffering capacity index (BCI) was determined by measuring the amount of acid
      necessary to produce a change of 5 micro equiv H(+) in the leaf homogenate. The
      BCI ranged from 883 micro equiv H(+) g(-1) for largetooth aspen to less than 105
      micro equiv H(+) g(-1) for sugar maple and balsam fir. Leaves of sugar maple and
      balsam fir had a lower internal pH and a higher percentage of ENC over BCI than
      paper birch and largetooth aspen. Overall, ENC was correlated with the
      concentration of all leaf nutrients except Ca, and BCI was correlated with Mg, N
      and Ca. The site effect was relatively unimportant for all variables.

PMID- 14969932
TI  - Characterization of nitrogenous solutes in tissues and xylem sap of Leucaena
      leucocephala.
AB  - Amino acid profiles of leaf, stem, and root tissues from nodulated and
      nonnodulated Leucaena leucocephala (Lam.) de Wit plants were determined by gas
      chromatography-mass spectrometry. High concentrations of mimosine and several
      other potentially toxic nonprotein amino acids, including pipecolic acid and two
      isomers of hydroxypipecolic acid, were identified in the tissues. Five
      metabolites remain unidentified. Of the foliar free amino acid nitrogen, 57-66%
      was associated with the potentially toxic amino acids. Major constituents in the
      leaf tissues of nonnodulated plants were mimosine and hydroxypipecolic acid
      (isomer 1). Mimosine was recovered in both the neutral plus basic and acidic
      amino acid fractions. Major differences between amino acid profiles of nodulated
      and nonnodulated roots were the low percentages of asparagine + aspartate (3.6%
      of the total pool compared to 33% in nodulated plants) and pipecolic acid in
      nonnodulated roots (1% of the total compared to 12.5% in nodulated plants). A
      novel plant betaine (dihydroxypipecolic acid betaine) was identified by fast-atom
      bombardment mass spectrometry in leaf tissues, albeit at relatively low
      concentrations (< 1 micro mol per gram fresh weight). Analyses of the xylem sap
      collected from nodulated plants confirmed that Leucaena is an asparagine
      transporter, as suggested by the high concentrations of asparagine and the low
      concentrations of ureides in its root nodules. Amino acid profiles of xylem sap
      from nonnodulated plants showed extremely low concentrations of asparagine +
      aspartate (0.12 micro mol ml(-1)), whereas asparagine + aspartate was the major
      constituent (4.38 micro mol ml(-1)) in the xylem sap of nodulated plants. Two
      nonprotein amino acids, pipecolic acid and hydroxypipecolic acid, were major
      constituents of the xylem sap of nodulated and nonnodulated plants, respectively.
      Three unidentified compounds detected in xylem sap samples from both nodulated
      and nonnodulated plants did not correspond with any of the peaks characterized
      from tissue samples.

PMID- 14969933
TI  - Variation in seedling hydraulic architecture as a function of species and
      environment.
AB  - Northern red oak (Quercus rubra L.) and yellow-poplar (Liriodendron tulipifera
      L.) were grown for two years in full sunlight (unshaded) or 20% of full sunlight
      (shaded) under either well-watered or drought conditions. There was a close
      association between evaporative flux (in situ) and leaf-specific conductivity
      (LSC) in stem segments of both species. Shaded, drought-stressed seedlings of
      both species had significantly reduced leaf area, evaporative flux, volume flow
      rate in xylem, flow velocity, potentially functional xylem area, and LSC than
      unshaded, well-watered seedlings. Reductions in LSC associated with drought or
      shade were similar for both species; and within a treatment, both species had
      similar LSC. Species differed in the manner of LSC adjustment to drought and
      shade. Reductions in leaf area associated with drought or shade were accompanied
      primarily by reductions in potentially functional xylem area for L. tulipifera,
      and by reductions in flow velocity for Q. rubra. These results suggest (1) the
      existence of a homeostatic balance between evaporative flux and LSC, (2) that
      species with widely different growth patterns and xylem anatomies may develop
      similar LSC within the same environment, and (3) a possible hydraulic basis for
      differences in habitat between ring- and diffuse-porous species.

PMID- 14969934
TI  - Leaf area and net photosynthesis during development of Prunus serotina seedlings.
AB  - We used the plastochron index to study the relationship between plant age, leaf
      age and development, and net photosynthesis of black cherry (Prunus serotina
      Ehrh.) seedlings. Leaf area and net photosynthesis were measured on all leaves
      >/= 75 mm of plants ranging in age from 7 to 20 plastochrons. Effects of plant
      developmental stage on leaf area and net photosynthesis were evaluated for leaves
      of differing age (horizontal series), leaves on plants of constant age (vertical
      series), and leaves of constant age (oblique series). Regression techniques were
      used to estimate leaf area from leaf blade dimensions. The best equations for
      predicting leaf area had R(2) values of 0.991-0.992 and used linear or
      logarithmic functions of both leaf length and width. Suitable, but less precise,
      equations with R(2) values of 0.946-0.962 were developed from either leaf length
      or leaf width. Leaf area development in black cherry seedlings was similar to
      that in other indeterminate species. Leaves of young plants reached full
      expansion at a lower leaf plastochron age than leaves of older plants. Maximum
      net photosynthesis per unit leaf area occurred 2-3 plastochrons before full leaf
      expansion. There was strong ontogenetic drift in net photosynthesis with leaf
      age; net photosynthesis decreased as plant age increased in leaves of the same
      plastochron age. Plots of the oblique series were particularly useful in
      providing information about interaction effects.

PMID- 14969935
TI  - Influence of (22S,23S)-homobrassinolide on rooting capacity and survival of adult
      Norway spruce cuttings.
AB  - To determine whether brassinosteroids promote clonal propagation of mature
      coniferous trees, cuttings of adult Norway spruce (Picea abies (L.) Karst.) trees
      were harvested in late March, treated with (22S,23S)-28-homobrassinolide (SSHB),
      and stored at 2 degrees C in darkness until they were planted in May. Treatment
      of the cuttings with SSHB significantly enhanced the formation of adventitious
      roots by increasing percent rooting from 50% in the control cuttings to 92% in
      the 60 ppm SSHB treatment. N(6)-Benzyladenine (BA) stimulated rooting slightly
      although not significantly, but it counteracted the stimulative effect of SSHB
      when cuttings were treated with both compounds together. In a second study, the
      above-ground parts of medium-sized mature clonal Norway spruce trees were
      pretreated from the end of June till August with SSHB or BA or both. Needle
      retention of cuttings taken from the pretreated trees the following spring was
      prolonged until September and the cuttings flushed, but did not root, whereas
      cuttings from untreated stock plants died before September. No interaction
      between BA and SSHB was observed. When these pretreatments were repeated the
      following year on the same mature clonal trees rooting of cuttings was
      significantly improved in the 5 ppm SSHB treatment.

PMID- 14969936
TI  - Early and late root formation in epicotyl cuttings of Pinus sylvestris after
      auxin treatment.
AB  - Auxin stimulated rooting of epicotyl cuttings of Pinus sylvestris irrespective of
      the physiological stage of the plant from which the cuttings were taken. The
      epicotyl cuttings were divided into two groups, those that differentiated roots
      early (within 6 weeks after cutting) and those that differentiated roots late
      (more than 6 weeks after cutting). Auxin treatment significantly stimulated the
      frequency of early rooting of epicotyl cuttings, whereas it had no effect on the
      frequency of late rooting of epicotyl cuttings. The number of roots per rooted
      cutting was significantly higher after auxin treatment both on early and late
      rooted cuttings. Anatomical studies showed that most of the roots on both early
      and late rooted cuttings developed from wound tissue. However some types of
      rooting were found only after auxin treatment of early rooted cuttings, e.g.,
      roots that developed from resin duct wound tissue or from vascular tissue or in
      the pith.

PMID- 14969937
TI  - Effect of ammonium on glutamine synthetase activity in ectomycorrhizal fungi, and
      in mycorrhizal and non-mycorrhizal Scots pine seedlings.
AB  - The influence of ammonium on glutamine synthetase activity (GS, EC 6.3.1.2) was
      studied in three species of ectomycorrhizal fungi, Paxillus involutus (Batsch:Fr)
      Fr, Piloderma croceum Erikss. and Hjortst. and Suillus variegatus (Fr) O Kuntze
      growing in pure culture, as well as in the roots and needles of nursery-grown,
      non-mycorrhizal and mycorrhizal Scots pine (Pinus sylvestris L.) seedlings
      inoculated with Paxillus involutus or Piloderma croceum as the symbiont. In
      response to increasing concentrations of ammonium in the nutrient solution, GS
      activity (expressed on a dry weight basis) increased slightly in Suillus
      variegatus but not in the other fungi. Glutamine synthetase activity increased in
      the roots and decreased in the needles of non-mycorrhizal seedlings as the
      ammonium concentration in the nutrient solution was increased from 0 to 1 mM, but
      no response was noted with further increases from 1 to 12 mM. Interspecies
      differences in GS activity were noted among the fungi growing in pure culture,
      but no significant interspecies differences were observed among the same fungi in
      the mycorrhizal state.

PMID- 14969938
TI  - Analysis of needle proteins and N-terminal amino acid sequences of two
      photosystem II proteins of western white pine (Pinus monticola D. Don).
AB  - A method is described for extracting needle proteins from mature western white
      pine (Pinus monticola D. Don) trees. Extracted proteins were separated into 26
      components by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The
      predominant protein component (32-39%) had a molecular weight of 57 kDa. The
      second most predominant protein component (14-25%) had a molecular weight of 16
      kDa. The amino acid composition of the twenty-six protein components was
      determined and a few selected proteins were subjected to further amino acid
      sequence analysis. Of these, two proteins, designated as Pin m I and Pin m II,
      were identified by sequence homology with other Photosystem II proteins. The Pin
      m I and Pin m II proteins had molecular weights of 22.6 kDa and 23.4 kDa,
      respectively. Pin m I had a much higher proline content than Pin m II.

PMID- 14969939
TI  - Influence of soil water on the physiological and morphological components of
      plant water balance in Populus trichocarpa, Populus deltoides and their F(1)
      hybrids.
AB  - Patterns of leaf growth, transpiration and whole-plant water balance in Populus
      trichocarpa, P. deltoides and their F(1) hybrids were studied during a soil
      drying cycle. Plant responses were analyzed during three distinct stages of
      dehydration. In stage I, the transpiration rate of drought-stressed plants
      remained constant and equal to that of well-watered plants even though soil water
      content declined by more than 40%. Stage II began as soil and plant water
      deficits induced stomatal closure. When soil water was expressed as a fraction of
      transpirable soil water, the transition from stage I to stage II occurred at soil
      water fractions of 0.35, 0.45 and 0.60 for P. trichocarpa, P. deltoides and their
      F(1) hybrids, respectively. Reductions in leaf growth coincided with the shift
      from stage I to stage II. As soil water declined further, decreases in relative
      transpiration and whole-plant leaf area were significantly greater in parental
      species than in F(1) hybrids. Inherent feedbacks controlling stomatal water loss
      and the maintenance and growth of leaf tissue appeared to differ between F(1) and
      parental genotypes in a pattern characteristic of an overdominant mode of
      inheritance.Stage III began once the ability of stomata to compensate for water
      loss had been exhausted. Substantial differences were found in plant survival
      during stage III, with F(1) hybrids surviving longer than parental species.
      Survival was more strongly correlated with the hydraulic conductivity of xylem
      tissues than with the dehydration tolerance of leaf tissues. Collectively, these
      responses suggest that F(1) hybrids were more drought resistant than either
      parental species and highlight the importance of whole-plant studies of
      functional relationships between plant growth, water balance and hydraulic
      conductivity.

PMID- 14969940
TI  - Modeling shoot water contents in high-elevation Picea rubens during winter.
AB  - During the winter of 1990-1991, a meteorological tower was established at an 880
      m elevation site within the spruce-fir zone on Mt. Moosilauke, New Hampshire,
      USA. Hourly means of air, needle and trunk temperatures, wind velocity, relative
      humidity and solar radiation were recorded. On a weekly basis, shoots that had
      elongated during the preceding growing season were collected from four red spruce
      (Picea rubens Sarg.) trees and their relative water contents (RWC) determined.
      Cuticular resistances of needles from these shoots were measured four times
      during the winter.Measured meteorological parameters were used in a previously
      developed model to simulate changes in red spruce shoot RWC during the winter.
      The modeled results were compared to measured shoot RWCs. The predictive power of
      the model was improved when it was modified to include measured values of
      cuticular resistance and needle and trunk temperatures. The new version of the
      model accurately predicted RWC from late December 1990 to the beginning of April
      1991, after which spring recharge appeared to occur. We conclude that water lost
      from foliage was easily replaced by stored reserves and that uptake of water by
      the roots was not required to maintain an adequate foliar water content during
      the winter.

PMID- 14969941
TI  - Production and nutrient dynamics of reproductive components of teak trees in the
      dry tropics.
AB  - Dry matter production and nutrient dynamics were quantified in the reproductive
      components of 14- and 30-year-old teak (Tectona grandis L.) stands growing in a
      dry tropical region. Flower production per tree was positively related to tree
      size. Despite massive flower production (33 x 10(6) and 171 x 10(6) ha(-1) year(
      1) in 14- and 30-year-old trees, respectively), only about 0.5-0.7% flowers
      developed into fruits. Immature fruit abscission totalled 34 and 58% of the total
      number of fruits initiated in the 14- and 30-year-old stands, respectively. The
      production of reproductive components (flowers, peduncles and fruits) was 245 kg
      ha(-1) year(-1) in the 14-year-old stand and 1122 kg ha(-1) year(-1) in the 30
      year-old stand. In both stands, relatively greater amounts of dry matter and
      nutrients were allocated to reproductive parts in September than in other months.
      Toward the end of the fruit maturation period, considerable nutrient resorption
      occurred. More than 90% of the nutrients accumulated in the peduncle were
      resorbed. Smaller amounts, ranging from 21% for K to 58% for N, were resorbed
      from mature, winged indehiscent fruits.

PMID- 14969942
TI  - Comparison of drought resistance among Prunus species from divergent habitats.
AB  - Root and shoot characteristics related to drought resistance were compared among
      cultivated peach (Prunus persica (L.) Batsch.), P. andersonii (Nevada Desert
      almond), P. besseyi (western sand cherry), P. maritima (beach plum), P.
      subcordata (Sierra or Pacific plum), and P. tomentosa (Nanking cherry). In all
      species, shoot characteristics were more closely associated with drought
      adaptation than root characteristics. The most xeric species, P. andersonii, had
      the lowest specific leaf area, smallest leaves, highest stomatal conductance
      (before stress), highest rate of carbon assimilation (A), high root length/leaf
      area and root weight/leaf area ratios, and the highest leaf nitrogen content on
      an area basis. Root hydraulic conductivity was similar for all species,
      indicating a lack of importance of this parameter for drought resistance. During
      a 5-7 day drought, water use efficiency (WUE) increased as shoot water potentials
      (Psi) declined to -3.0 to -4.0 MPa for the xeric P. andersonii and P. subcordata,
      whereas after an initial increase, WUE decreased with declining Psi in the -1.5
      to -3.0 MPa range for the more mesic P. maritima, P. persica and P. tomentosa as
      a result of non-stomatal limitations to A. Carbon assimilation rate decreased
      linearly with Psi during drought in all species, but the Psi at which A reached
      zero was not associated with drought adaptation. We conclude that the variation
      in leaf characteristics among Prunus species could be exploited to improve the
      drought resistance of commercial cultivars.

PMID- 14969943
TI  - Photosynthetic capacity of leaves of Eucalyptus globulus (Labill.) growing in the
      field with different nutrient and water supplies.
AB  - The effects of water and nutrient availability on photosynthetic capacity of
      juvenile and adult leaves of Eucalyptus globulus Labill. seedlings were evaluated
      by measuring oxygen evolution at light and CO(2) saturation. Seedlings supplied
      with near optimal amounts of water and nutrients had higher growth rates than non
      irrigated, unfertilized control seedlings, but photosynthetic capacity was
      similar in both treatments. Differences in foliar nitrogen concentrations between
      the two treatments were minor, which largely explains why the growth response to
      near optimal nutrition was not associated with an increase in photosynthetic
      capacity per unit leaf area. Nevertheless, the photosynthetic capacity of
      juvenile leaves decreased from distal to proximal positions in the mid-crown and
      was positively correlated with leaf nitrogen concentration expressed on a leaf
      surface area basis. During the dry season, non-irrigated, unfertilized seedlings
      fixed carbon at lower rates than irrigated seedlings supplied with near optimal
      nutrition because of stomatal closure even though photosynthetic capacity was
      unaffected by water deficits. In both treatments, there were differences between
      the photosynthetic capacity of adult and juvenile leaves that were largely
      explained by the low specific leaf area of adult leaves.

PMID- 14969944
TI  - Effects of litter from a tropical rainforest on tree seed germination and
      establishment under controlled conditions.
AB  - The effects of litter cover on the germination of seeds of three tropical
      rainforest, pioneer tree species (Cecropia obtusifolia, Heliocarpus
      appendiculatus and Piper auritum) was investigated. Germination of seeds of all
      tree species was partially or totally inhibited when the seeds were covered with
      litter, whereas uncovered seeds or seeds covered with paper instead of litter
      germinated. Seed size was directly correlated with the capacity of the germinated
      seeds to emerge through the litter. In soil experiments in the greenhouse,
      seedling emergence from the soil was inhibited by the presence of litter on the
      soil surface.

PMID- 14969945
TI  - Root growth and water use efficiency of Douglas-fir (Pseudotsuga menziesii
      (Mirb.) Franco) and lodgepole pine (Pinus contorta Dougl.) seedlings.
AB  - One-year-old Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) and lodgepole
      pine (Pinus contorta Dougl.) seedlings were grown for 17 weeks in 100-cm deep,
      7.8-liter containers. Two Douglas-fir provenances, one from a wet and one from a
      dry site in coastal British Columbia, and two lodgepole pine provenances, one
      from a wet and one from a dry site in interior British Columbia, were grown in
      wet (522% water content) or dry (318% water content) peat/vermiculite soil in a
      factorial design. Each container was sealed so that water loss occurred only
      through the seedling. Five harvests were made at three to five week intervals and
      water use, dry matter increment, root length and root weight were determined at
      each harvest. Stomatal conductance and shoot water potentials were measured
      during the last 12 weeks of the experiment. Lodgepole pine seedlings had greater
      dry matter production, water use, stomatal conductance and new root length than
      Douglas-fir seedlings. New root weight of lodgepole pine seedlings exceeded that
      of Douglas-fir seedlings during the last five weeks of the experiment, and
      specific root length (root length per unit root weight) of new roots was higher
      for lodgepole pine seedlings throughout the experiment. Douglas-fir seedlings
      showed higher water use efficiency (WUE) than lodgepole pine seedlings, and both
      species showed higher WUE in the dry soil treatment. Douglas-fir seedlings had
      lower water potentials and higher water uptake rates per unit of new root length
      than lodgepole pine seedlings, although water uptake rates per unit of root dry
      weight showed little difference between species. Soil water treatment influenced
      specific root length of new roots, water uptake per unit of new root length, and
      WUE in Douglas-fir seedlings more than in lodgepole pine seedlings.

PMID- 14969946
TI  - A rapid technique for recording and measuring the leaf area of conifer needle
      samples.
AB  - An optical planimetric technique for measuring projected leaf area of conifer
      needle samples was developed that combines a rapid field recording method with an
      inexpensive hand-held optical scanner. The field recording method utilizes strips
      of diazo paper (blueprint paper), 10 x 28 cm, to make positive images of the
      needle samples. An analysis program calculates leaf area from the output files
      produced by the hand-held scanner. The results from this system were compared
      with results from a Li-Cor 3100 leaf area meter and from a digital camera-based
      image analysis system using both standard samples of known area and needle
      samples from three conifer species. All three systems produced similar results in
      terms of means and variances. The digital camera system typically had the lowest
      variances between successive measurements of the same sample. Most differences
      among the systems were not statistically significant. The system presented in
      this paper is inexpensive, easy to use, and provides a rapid and permanent method
      for recording and measuring the leaf area of conifer samples.

PMID- 14969947
TI  - Mild ozone exposure alters (14)C dynamics in foliage of Pinus taeda L.
AB  - To explore the physiological mechanisms underlying ozone-induced growth
      reductions in loblolly pine (Pinus taeda L.), seedlings were exposed to sub
      ambient (charcoal-filtered), ambient or twice-ambient ozone in open-top chambers
      for three growing seasons. In the final year of exposure, current-year needle
      fascicles were labeled with (14)CO(2) and the incorporation of (14)C into
      biochemical fractions was followed for 48 hours. Irrespective of ozone treatment,
      losses of (14)C-assimilates from foliage to respiration and translocation were
      minimal during the first 3 hours, whereas more than 60% of the label was lost
      during the next 45 hours. Radiolabel in sugar decreased rapidly after a lag
      period, roughly paralleling the pattern of total (14)C loss. The amount of (14)C
      label in starch and lipids plus pigments remained constant throughout the 48-hour
      chase period, whereas the amount of (14)C label in other fractions showed a net
      decrease over the 48-hour chase period. Ozone treatments altered foliar carbon
      dynamics in two ways: (1) ozone exposure increased foliar (14)C retention up to
      21% for the first 5 hours after labeling, but not thereafter, and (2) ozone
      exposure decreased partitioning of (14)C into starch and increased partitioning
      of (14)C into organic acids, residue, and lipids plus pigments, indicating an
      intensified partitioning of carbon to injury and repair processes. Both short
      term carbon retention and diversion of carbon from storage compounds to repair
      processes are foliar mechanisms by which ozone exposure could decrease growth in
      loblolly pine seedlings.

PMID- 14969948
TI  - Relationship between freezing tolerance and shoot water relations of western red
      cedar.
AB  - Freezing tolerance and shoot water relations parameters of western red cedar
      (Thuja plicata Donn) seedlings were measured every 2 weeks from October 1989 to
      April 1990. Freezing tolerance, measured by freeze-induced electrolyte leakage,
      showed seasonal shifts in the temperature causing 50% foliage electrolyte leakage
      (LT(50)). The LT(50) value was -4 degrees C in October, it decreased to -20
      degrees C in February and then increased to -6 degrees C in April. The foliage
      index of injury at -10 degrees C (II(-10)) also showed seasonal shifts from a
      high of 98% in October to a low of 18% in February followed by an increase to 82%
      in April. Osmotic potentials at saturation (Psi(s(sat))) and turgor loss point
      (Psi(s(tlp))) were, respectively, -1.07 and -1.26 MPa in October, -1.57 and -2.43
      MPa in January, and -1.04 and -1.86 MPa in April. Dry weight fraction (DWF)
      increased and symplastic volume at full turgor (V(o)) decreased during the fall
      winter acclimation phase, whereas DWF decreased and V(o) increased during the
      late winter-spring deacclimation phase. Relationships between seasonal patterns
      of freezing tolerance and shoot water relations parameters showed that LT(50) and
      II(-10) decreased linearly as Psi(s(tlp)) and V(o) decreased and DWF increased.
      There was no discernible difference in the relationship during fall acclimation
      or spring deacclimation. The freezing dehydration index at -10 degrees C (FDI(
      10)) declined from 0.69 in November to 0.41 in February and increased to 0.56 in
      April. The value of II(-10) decreased linearly as FDI(-10) decreased, although a
      measurement made on actively growing spring foliage did not fit this
      relationship. The results indicate that seasonal changes in freezing tolerance of
      western red cedar are partially due to changes in tissue water content,
      symplastic volume, passive osmotic adjustment and FDI(-10).

PMID- 14969949
TI  - Seasonal differences in freezing stress resistance of needles of Pinus nigra and
      Pinus resinosa: evaluation of the electrolyte leakage method.
AB  - Seasonal changes in freezing stress resistance of needles of red pine (Pinus
      resinosa Ait.) and Austrian pine (Pinus nigra Arnold) trees were measured by an
      electrolyte leakage method and by visual observation. During most of the year,
      freezing stress resistance determined by the two methods gave similar results.
      The electrolyte leakage method provided a good estimate of seasonal changes in
      freezing stress resistance except for red pine needles in their most winter-hardy
      state. To obtain a reliable estimate of freezing stress resistance in winter
      hardy red pine needles it was necessary to combine the electrolyte leakage method
      with visual observations. When red pine needles survived exposure to -80 degrees
      C or lower, electrolyte leakage was never more than 30% even when the needles
      were exposed to a slow freeze-thaw stress of -196 degrees C. However, rapid
      freezing of red pine needles to -196 degrees C resulted in electrolyte leakage of
      over 80%. Red pine needles attained a much higher freezing stress resistance
      during the winter than Austrian pine. Red pine needles also acclimated and
      deacclimated faster than Austrian pine needles. An index of injury was developed
      based on the electrolyte leakage method ((R(2) + R(1))/2, where R(1) is the
      minimum % electrolyte leakage from noninjured tissue and R(2) is the maximum %
      electrolyte leakage at the highest injury) that reliably predicted freezing
      stress resistance of pine needles for most of the year. Important aspects for
      developing a successful index of injury for pine needles are: use of cut needles,
      vacuum infiltration and shaking during incubation in water.We conclude that: (1)
      during cold acclimation the cell wall properties of the pine needles changed and
      these changes, which appeared to differ in the two species, might explain the
      very low leakage of electrolytes from winter-hardy needles of red pine; (2) pine
      needles survive winter by developing the ability to tolerate extracellular ice
      formation, because after rapid freezing the needles were severely injured; and
      (3) red pine is adapted to a shorter growing season and colder winters than
      Austrian pine.

PMID- 14969950
TI  - Growth and phenology of seedlings of four contrasting slash pine families in ten
      nitrogen regimes.
AB  - Seedlings of two fast- and two slow-growing families of slash pine, Pinus
      elliottii Englm. var. elliottii, were grown in a greenhouse for one growing
      season in one of 10 nitrogen (N) regimes. Increasing the N concentration in the
      nutrient solution resulted in both increased growth rates during the exponential
      growth phase and extended duration of the growing season. The two components of
      total height, free growth (epicotyl length to the first bud) and summer growth
      (height growth after the first bud), both increased significantly with increasing
      N concentrations up to 40-60 mg l(-1) but decreased at N concentrations above 180
      mg l(-1). Compared to seedlings grown in the presence of an optimum N
      concentration, seedlings grown in the presence of trace amounts of N were smaller
      and had less summer growth as a percentage of total growth, earlier cessation of
      height growth, fewer flushes, lower shoot/root ratio, higher root fibrosity, and
      lower N concentrations in all seedling tissues. Compared to slow-growing
      families, fast-growing families had more summer height growth, more flushes and
      later growth cessation, higher shoot/root ratios and higher root fibrosity at all
      N concentrations. In the presence of an optimum or higher concentration of N, the
      fast-growing families also had higher needle and total N concentrations than the
      slow-growing families. Strong family by N-treatment interactions occurred for
      height, phenology and biomass traits because of the extra responsiveness of one
      family to increasing N concentration. Several seedling traits were identified
      that appear promising for predicting field performance in slash pine. The results
      indicated that the nutrient environment greatly influences genetic expression
      (e.g., family patterns of summer growth were most closely related to field
      rankings for seedlings in the trace-N treatment).

PMID- 14969951
TI  - The impact of water and nutrient deficiencies on the growth, gas exchange and
      water relations of red oak and chestnut oak.
AB  - Red oak (Quercus rubra), a mesic species, and chestnut oak (Quercus prinus), a
      xeric species, were grown in a greenhouse with and without fertilizer (F+ and F-,
      respectively) and subjected to a 10-week drydown (W-) or kept well watered (W+).
      In both species, fertilized seedlings exhibited greater reductions in mean net
      photosynthesis (A), leaf conductance (g(wv)), leaf water potential (Psi(leaf))
      and water use efficiency (WUE) during the drydown than unfertilized seedlings. In
      the W- treatments, red oak showed greater reductions in A, g(wv) and Psi(leaf)
      than chestnut oak. Differential fertilization of the seedlings of both species
      had a greater effect on tissue water relations than differential watering. During
      the latter weeks of the drydown, there was no osmotic adjustment in red oak, but
      chestnut oak in the F+/W- treatment had significantly lower osmotic potentials at
      full and zero turgor than seedlings in any of the other treatments. The results
      indicate that high nutrient availability does not improve the drought tolerance
      of these two oak species.

PMID- 14969952
TI  - Leaf water status and root system water flux of shortleaf pine (Pinus echinata
      Mill.) seedlings in relation to new root growth after transplanting.
AB  - Water relations and root growth of shortleaf pine (Pinus echinata Mill.) were
      studied four weeks after seedlings from a half-sib family had been transplanted
      to one of three regimes of soil water availability at a root zone temperature of
      either 15 or 20 degrees C. About one-third of the variation in new root growth
      was explained by the root zone environment. The interaction between root zone
      temperature and soil water availability accounted for 10% of the variation in new
      root growth. In the most favorable root environment, new roots averaged 620 mm(2)
      of projected surface area. Leaf water potential increased exponentially with new
      root projected surface area, becoming constant at about 300 mm(2). Leaf
      conductance and root system water flux increased linearly with new root growth.

PMID- 14969953
TI  - Effects of copper and cadmium on uptake and leakage of K(+) in birch (Betula
      pendula) roots.
AB  - Uptake and leakage experiments were performed to study the effects of copper and
      cadmium on K(+) fluxes in birch (Betula pendula Roth) roots. Labeled rubidium
      ((86)Rb(+)) was used as a tracer for K(+). Plants were pretreated with Cu or Cd
      (0, 2, 5 or 25 microM) for 0-300 min and then transferred to radiolabeled
      nutrient solution (150 microM K(+)) with or without 2,4-dinitrophenol (DNP) to
      separate the effects of heavy metal on active and passive K(+) influxes. Passive
      K(+) influx was decreased by pretreatment with Cu but was only slightly affected
      by pretreatment with Cd. Pretreatment with 2 microM Cu increased active K(+)
      influx, whereas pretreatment with 25 microM Cu decreased active K(+) influx and
      intermediate Cu concentrations (5 microM) did not affect active K(+) influx. The
      pretreatment effects of Cu on active and passive K(+) influxes increased with
      increasing pretreatment time. During the first hour, pretreatment with Cd
      decreased active K(+) influx with increasing pretreatment time, whereafter
      recovery began. To measure K(+) efflux, birch plants were loaded with (86)Rb(+)
      for 7 days before being exposed to Cu or Cd (0, 1, 3, 5 or 10 microM) in
      unlabeled nutrient solutions for 24 h. Net efflux of K(+) was measured as
      (86)Rb(+)-activity in the nutrient solutions 24 h after a heavy metal had been
      introduced. Efflux of K(+) increased with increasing Cu or Cd concentration in
      the unlabeled nutrient solution.The data indicate that Cu and Cd affected K(+)
      influx differently and that recovery mechanism(s), which were induced shortly
      after heavy metal introduction, counteracted the heavy-metal induced inhibition
      of active K(+) influx. Efflux of K(+) from plant roots over a 24-h period
      indicated that Cu and Cd had similar effects on K(+) efflux. There was no
      evidence of a recovery mechanism counteracting the heavy-metal-induced inhibition
      of K(+) efflux.

PMID- 14969954
TI  - A leaf phosphorus assay for seedlings of Acacia mangium.
AB  - Concentrations of extractable and total phosphorus in leaves, stem, root and
      nodules of 12-week-old seedlings of two provenances of Acacia mangium Willd. were
      analyzed to identify the fraction of phosphorus and the plant part most suitable
      for predicting the phosphorus nutritional status of the seedlings.For both
      provenances, concentrations of extractable phosphorus were more sensitive to
      changes in soil phosphorus status and varied less among different plant parts
      than concentrations of total phosphorus. Concentrations of extractable phosphorus
      in the youngest fully expanded leaf (Leaf 3 from the apex) and the next two older
      leaves correlated closely with seedling dry mass and may be used to assess the
      phosphorus nutritional status of Acacia mangium seedlings.

PMID- 14969955
TI  - Abscisic acid accumulation in leaves of two contrasting hybrid poplar clones
      affected by nitrogen fertilization plus cyclic flooding and soil drying.
AB  - Cuttings of hybrid Populus clones Tristis and Eugenei growing in pots in a
      greenhouse were treated with nitrogen fertilizer at two rates and subjected to
      repeated soil flooding or drying. Periodically, gas exchange measurements and
      radioimmunoassays, to determine abscisic acid (ABA) concentrations, were made on
      recently mature leaves.In both clones, photosynthesis and stomatal conductance
      were depressed five days after flooding, but leaf ABA concentrations remained
      relatively constant. In contrast, an initial, 9-day period of soil drying
      resulted in substantial ABA accumulation in leaves, which closely correlated with
      declines in photosynthesis and conductance. A second soil drying cycle of up to 9
      days was less effective in modifying gas exchange and leaf ABA concentrations.
      High-N supply stimulated leaf ABA production as the soil dried. On the resumption
      of watering, gas exchange in Tristis recovered fully and rapidly and leaf ABA
      concentrations quickly returned to control values, whereas gas exchange in
      Eugenei recovered slowly and leaf ABA concentrations remained high for longer.Gas
      exchange in Eugenei was unaffected by soil drying until leaf ABA concentrations
      exceeded 100 ng g(dw) (-1), whereas Tristis showed a reduction in stomatal
      conductance and photosynthesis at leaf ABA concentrations of only 10 ng g(dw) (
      1). A rise in internal CO(2) concentrations was associated with increased leaf
      ABA concentrations in Tristis, but not in Eugenei. Clonal differences in the
      relationship between gas exchange and leaf ABA concentration suggest contrasting
      physiological strategies for survival under prolonged drying conditions.

PMID- 14969956
TI  - Diurnal variation in extension growth of leaves of Salix viminalis.
AB  - Diurnal variation in leaf extension and biophysical parameters of leaf growth
      were measured in young leaves from a stand of Salix viminalis L. in southern
      Sweden over a two-day period of clear skies during late July. Leaf growth rate
      (irreversible extension) was greatest during the late afternoon and early
      evening, falling to negligible values during the night and early morning.Leaf
      water potential and leaf osmotic potential showed declining values in the morning
      with subsequent recovery in the late afternoon. Diurnal variation in osmotic
      potential (-1.3 to -1.7 MPa) was small compared with that of leaf water potential
      (-0.1 to -1.2 MPa). Calculated values of leaf turgor pressure during the night
      (1.2 MPa) were double the midday values. Growth rate correlated poorly with
      turgor, which (except on one occasion) was always above a calculated value of
      yield turgor at 0.53 MPa.Diurnal variation in extension growth rate was large
      compared with that in plastic extensibility of leaf tissue as measured by an
      Instron technique. Values of extensibility were low and showed little diurnal
      variation, which is consistent with a proposed negative feedback of expansive
      growth rate on extensibility. Extension growth rate correlated well with air
      temperature, suggesting that the rate of leaf expansion may have been limited by
      a temperature-dependent rate of cell wall loosening.

PMID- 14969957
TI  - Photosynthesis and water relations of the floodplain tree, boxelder (Acer negundo
      L.).
AB  - During summer, gas exchange and water relations were measured in mature boxelder
      (Acer negundo L.) trees growing on a floodplain in central Indiana, USA. A
      shallow (< 1.25-m deep) water table and repeated flooding kept the soil water
      potential above -0.5 MPa at all times. Net photosynthesis and stomatal
      conductance were influenced primarily by light and, to a lesser extent, by leaf
      temperature, but showed no relationships with leaf-to-air water vapor gradient or
      leaf water potential. Throughout the summer, there was no midday stomatal closure
      on any measurement day, and leaf water potential at dawn and minimum daily leaf
      water potential remained above -0.4 and -1.4 MPa, respectively. Nevertheless,
      there was a seasonal decline in leaf osmotic potentials at saturation and turgor
      loss point. Seasonal changes in maximum daily net photosynthesis and stomatal
      conductance, minimum daily leaf water potential and soil-to-leaf hydraulic
      conductance were not related to seasonal changes in soil water potential, air or
      soil temperature, or water table depth. Seasonal responses of net photosynthesis
      to intercellular CO(2) indicated that net photosynthesis was controlled primarily
      by nonstomatal factors. High soil water and a shallow water table may have kept
      soil-to-leaf hydraulic conductance large (5-9 mmol m(-1) s(-1) MPa(-1))
      throughout the summer, permitting the trees to keep their stomata open, yet
      maintain leaf turgor and high net photosynthesis during the hot, low-humidity
      afternoons. This could also account for the dominance of nonstomatal influences
      on net photosynthesis.

PMID- 14969958
TI  - Characterization of glutathione S-transferase from dwarf pine needles (Pinus mugo
      Turra).
AB  - Glutathione S-transferase activity conjugating xenobiotics with glutathione (GSH)
      was found in extracts from needles of dwarf pine (Pinus mugo Turra). In vivo
      incubation of needle segments with the herbicide fluorodifen at 25 degrees C
      resulted in conversion of the xenobiotic to water-soluble products at initial
      rates of 0.7 nmol h(-1) g(fw) (-1). At 15 degrees C, the initial rate of product
      formation was decreased to 0.1 nmol h(-1) g(fw) (-1). In vitro conjugation
      studies with chloro-2,4-dinitrobenzene (CDNB) and 1,2-dichloro-4-nitrobenzene
      (DCNB) as model substrates gave apparent K(m) values of 0.5 mM GSH and 1.14 mM
      CDNB in the GSH/CDNB system and 0.3 mM GSH and 0.44 mM DCNB in the GSH/DCNB
      system. The pH optimum was between 7.7 and 7.9 for both the GSH/CDNB and the
      GSH/DCNB systems. The temperature optimum for these model substrates was between
      30 and 35 degrees C, and only minute amounts of enzyme activity were detected at
      15 degrees C. The activation energy in the temperature range of 15 to 30 degrees
      C was 46 kJ mol(-1). Dwarf pine glutathione S-transferase exhibited an
      approximate molecular weight of 52 kD.

PMID- 14969959
TI  - Soil water content, soil strength and the growth of elm root suckers.
AB  - The elongation rate of root suckers of Dutch elm (Ulmus x hollandica Mill.)
      increased with increasing age of the sucker, soil water content and net growth
      pressure (the excess of turgor pressure over soil restraining pressure) and it
      decreased with increasing soil strength. The increase in the rate of sucker
      elongation with age was probably the result of a decrease in osmotic potential
      causing an increase in the turgor pressure. Increasing soil strength increased
      the rate of osmotic adjustment. The increase in the rate of sucker elongation
      with increasing soil water content was probably due to an increase in the water
      potential of the sucker and a decrease in soil strength associated with
      increasing soil water content.

PMID- 14969960
TI  - Absorption and assimilation of nitrate and ammonium ions by jack pine seedlings.
AB  - Jack pine (Pinus banksiana Lamb.) seedlings were grown in a shaded or unshaded
      light regime with either NO(3) (-)- or NH(4) (+)-N as the sole N source. After
      three months, seedlings grown with NH(4) (+)-N were larger than seedlings grown
      with NO(3) (-)-N. Irradiance had a greater effect on growth of ammonium-fed
      seedlings than on growth of nitrate-fed seedlings.At all times from 6 to 24 h
      following incorporation of (15)N, soluble, insoluble, and total (15)N contents of
      shoots and roots were higher in ammonium-fed seedlings than in nitrate-fed
      seedlings. The pattern of (15)N accumulation in shoots was similar to that in
      roots. After 6 and 24 h of (15)N incorporation, unshaded, ammonium-fed seedlings
      had 8.8 and 2.8 times greater total (15)N contents, respectively, than unshaded,
      nitrate-fed seedlings. In response to shading, ammonium-fed seedlings increased
      their total uptake of (15)N per unit root weight, whereas nitrate-fed seedlings
      did not. No nitrate or (15)NO(3) (-) was detected in any plant tissue. Nitrate
      fed plants had higher NH(4) (+), Asp, and Gln concentrations in needles and
      higher gamma-aminobutyric acid and Arg concentrations in stems. Accumulation of
      (15)N in roots was not affected by the pH of the (15)N solution or by the N
      source fed to the seedlings before the period of (15)N incorporation. Thus NO(3)
      (-) transport into roots, rather than its reduction or transport within the
      plant, seems to be the factor limiting the growth of jack pine supplied with
      NO(3) (-)-N as the sole N source.

PMID- 14969961
TI  - Integration of sapflow velocity in elliptical stems.
AB  - The estimation of water flux through the stem of a plant by point estimates based
      on the heat pulse technique requires integration of the velocity profile. The
      polynomial integration method and the weighted average technique both assume
      radial symmetry about the bole. A method is introduced that solves the equations
      for the ellipse in the weighted average technique, and includes an optimizing
      algorithm for the placement of sensors. The sensitivity of sapflow estimates
      through stems to increasing eccentricity is examined by means of analytical
      solutions and simulation. The error in sap flux measurement resulting from the
      radial approximation of the sapwood conducting area is expressed analytically and
      shown to be small over the range of eccentricities (e < 0.8) expected in nature.
      Simulations where radial symmetry is assumed for elliptical stems show
      substantial error in mean velocity (and thus flux) with modest eccentricities (e
      > 0.4).

PMID- 14969962
TI  - Gibberellin A(4/7) promotes cone production on potted grafts of eastern white
      pine.
AB  - Potted grafts of eastern white pine (Pinus strobus L.) growing in a heated
      greenhouse were sprayed weekly with 0, 250 or 500 mg l(-1) of gibberellin A(4/7)
      for four different 6-week periods between mid-May and mid-September. At different
      periods, gibberellin A(4/7) concentrations of 250 and 500 mg l(-1) were effective
      in promoting pollen- and seed-cone production. Spraying in May and June, during
      the period of rapid terminal shoot elongation, significantly increased pollen
      cone production, whereas spraying in August and September, about a month after
      terminal shoot elongation, significantly increased seed-cone production.

PMID- 14969963
TI  - Influence of hydroponic culture method on morphology and hydraulic conductivity
      of roots of honey locust.
AB  - The morphology and hydraulic conductivity of root systems of Gleditsia
      triacanthos L. var. inermis Willd. (honey locust) grown hydroponically in sand
      and solution cultures were compared. Total root system length was similar in the
      two cultures. However, root systems grown in solution had longer primary roots,
      fewer lateral roots and root hairs, and a greater distance between the tip of the
      primary root and the junction of the youngest secondary root and the primary root
      than root systems grown in sand. Hydraulic conductivities of root systems grown
      hydroponically for 21 or 35 days in sand or solution culture were similar. These
      findings show that different methods of hydroponic culture can affect root
      morphology without altering root resistance to water transport.

PMID- 14969964
TI  - Effects of radiational heating at low air temperature on water balance, cold
      tolerance, and visible injury of red spruce foliage.
AB  - Recent studies have shown that winter needle mortality in red spruce (Picea
      rubens Sarg.) is increased by exposure to direct solar radiation, possibly as a
      result of photo-oxidative damage, accelerated winter desiccation, or reduced cold
      tolerance due to heating of sun-exposed needles. In an experiment at controlled
      subfreezing air temperatures of -10 to -20 degrees C, visible radiation was less
      effective than infrared radiation in producing needle desiccation and visible
      injury during freeze-thaw cycles. However, visible radiation produced a red-brown
      color in injured needles, similar to natural winter injury, whereas injured
      needles exposed to infrared radiation were yellow and injured needles kept in
      darkness were dark brown. Thus, visible radiation was necessary to produce the
      red-brown color of damaged needles, but not the injury itself. Needle desiccation
      was not strongly correlated with visible injury, but the pattern of variation in
      visible injury among trees and the positive correlation between electrolyte
      leakage and visible injury suggested that freezing damage following freeze-thaw
      cycles might cause the visible injury. This was confirmed by a second experiment
      that showed loss of cold hardiness in needles thawed by radiational heating for
      six consecutive days. Even with a constant nighttime temperature of -10 degrees
      C, six days of radiational heating of needles to above freezing caused a small
      (2.8 degrees C) mean decrease in needle cold tolerance, as measured by
      electrolyte leakage. Continuous darkness at -10 degrees C for six days resulted
      in an estimated 5.6 degrees C mean increase in needle cold tolerance. Freezing
      injury stimulated desiccation: cooling at 4 degrees C h(-1) to -43 or -48 degrees
      C increased the dehydration rate of isolated shoots by a factor of two to three
      during the first day after thawing. Within three days at 15 to 22 degrees C and
      50% relative humidity, the mean water content of these shoots fell to 60% or
      lower, compared to 90% or greater for unfrozen controls or shoots subject to less
      severe freezing stress. In some but not all severely freeze-stressed shoots,
      accelerated needle desiccation and abscission were accompanied by a red-brown
      color typical of red spruce winter needle injury. We conclude that severe winter
      desiccation in red spruce may often be due to prior freezing injury, increased as
      a result of exposure to direct solar radiation. Furthermore, freezing injury in
      red spruce may sometimes cause desiccation and abscission of green needles.

PMID- 14969965
TI  - Effects of varying crop load on photosynthesis, dry matter production and
      partitioning of Crispin/M.27 apple trees.
AB  - Fruit load was altered by flower thinning on three- and four-year-old, field
      grown apple trees. Increasing fruit load led to increases in dry matter
      production per unit leaf area and partitioning to fruit and to decreases in fruit
      size, percentage fruit dry matter, dry matter partitioning to new shoot growth,
      thickening of existing woody tissue and root growth. Flower bud production for
      the following spring was also negatively affected by an increase in fruit load.
      Leaf photosynthesis was increased in cropping trees in July and August at the
      time of maximum fruit dry weight increase. Calculated light interception was
      linearly related to leaf area. The efficiency of conversion of intercepted
      photosynthetic active radiation to dry matter energy equivalents was 3.3% in
      heavily cropping trees and 1.8% in non-cropping trees. Total dry matter
      production was linearly related to both leaf area and light interception, but the
      variance accounted for by the regression was more than doubled if fruit dry
      matter or fruit number was included in the regression.

PMID- 14969966
TI  - Biochemical composition of loblolly pine reflects pollutant exposure.
AB  - Under experimental conditions, the growth of loblolly pine (Pinus taeda L.) is
      often responsive to ozone at near-ambient concentrations. However, little is
      known of the biochemical changes associated with this or other pollutants.
      Loblolly pine seedlings in open-top chambers were exposed to combinations of
      ozone (sub-ambient, ambient, or twice-ambient), acidic precipitation (pH 3.8 or
      pH 5.2) and soil magnesium (0.15 or 0.32 microg g(-1) exchangeable Mg) for three
      growing seasons. The effects of these treatments were greater in foliage than in
      stems or roots. The largest treatment effect was a 50% decrease in the starch
      concentration of current-year foliage from the twice-ambient ozone treatment
      compared with current-year foliage from the sub-ambient ozone treatment.
      Responses to ozone were consistent with the hypothesis that ozone-induced growth
      reductions are associated with depletion of carbohydrate reserves resulting from
      injury compensation and repair processes or reduced carbon fixation or both.
      Addition of acidic precipitation, and to a small extent Mg, decreased sugar
      concentrations of tissues; however, this effect appeared to be mediated by
      nutrient addition rather than by acidity per se. Given the role of carbohydrates
      in plant resistance to environmental stress, the sensitivity of carbohydrates to
      experimental treatments demonstrates the potential for indirect effects of ozone,
      acidic precipitation, and soil properties on stress resistance. Noncarbohydrate
      constituents were largely unresponsive to the experimental treatments. These
      findings imply that tissue carbohydrate analysis may be useful for assessing the
      impacts of pollutants in forest ecosystems.

PMID- 14969967
TI  - Carbon sequestration in the trees, products and soils of forest plantations: an
      analysis using UK examples.
AB  - A carbon-flow model for managed forest plantations was used to estimate carbon
      storage in UK plantations differing in Yield Class (growth rate), thinning regime
      and species characteristics. Time-averaged, total carbon storage (at equilibrium)
      was generally in the range 40-80 Mg C ha(-1) in trees, 15-25 Mg C ha(-1) in above
      and belowground litter, 70-90 Mg C ha(-1) in soil organic matter and 20-40 Mg C
      ha(-1) in wood products (assuming product lifetime equalled rotation length). The
      rate of carbon storage during the first rotation in most plantations was in the
      range 2-5 Mg C ha(-1) year(-1).A sensitivity analysis revealed the following
      processes to be both uncertain and critical: the fraction of total woody biomass
      in branches and roots; litter and soil organic matter decomposition rates; and
      rates of fine root turnover. Other variables, including the time to canopy
      closure and the possibility of accelerated decomposition after harvest, were less
      critical. The lifetime of wood products was not critical to total carbon storage
      because wood products formed only a modest fraction of the total.The average
      increase in total carbon storage in the tree-soil-product system per unit
      increase in Yield Class (m(3) ha(-1) year(-1)) for unthinned Picea sitchensis
      (Bong.) Carr. plantations was 5.6 Mg C ha(-1). Increasing the Yield Class from 6
      to 24 m(3) ha(-1) year(-1) increased the rate of carbon storage in the first
      rotation from 2.5 to 5.6 Mg C ha(-1) year(-1) in unthinned plantations. Thinning
      reduced total carbon storage in P. sitchensis plantations by about 15%, and is
      likely to reduce carbon storage in all plantation types.If the objective is to
      store carbon rapidly in the short term and achieve high carbon storage in the
      long term, Populus plantations growing on fertile land (2.7 m spacing, 26-year
      rotations, Yield Class 12) were the best option examined. If the objective is to
      achieve high carbon storage in the medium term (50 years) without regard to the
      initial rate of storage, then plantations of conifers of any species with above
      average Yield Classes would suffice. In the long term (100 years), broadleaved
      plantations of oak and beech store as much carbon as conifer plantations. Mini
      rotations (10 years) do not achieve a high carbon storage.

PMID- 14969968
TI  - Vulnerability of several conifers to air embolism.
AB  - Hydraulic properties of xylem in seven species of conifer were studied during
      late winter and early spring 1991. Vulnerability to cavitation and air embolism
      was investigated using hydraulic conductivity and acoustic techniques. Embolisms
      were induced in branches excised from mature trees by air-drying them in the
      laboratory. Both techniques gave comparable results indicating that they both
      assess the same phenomenon. Within a tree, vulnerability was related to the
      permeability of the xylem, the largest stems tended to cavitate before the
      smallest ones when water deficits developed in a branch. Interspecific
      comparisons showed large differences in the xylem water potential needed to
      induce significant embolism, values ranged from -2.5 MPa in Pinus sylvestris to 
      4 MPa in Cedrus atlantica, but these differences did not correlate with
      differences in the xylem permeability of the species. The vulnerability of a
      species to air embolism was found to be consistent with its ecophysiological
      behavior in the presence of water stress, drought-tolerant species being less
      vulnerable than drought-avoiding species.

PMID- 14969969
TI  - Carbon dioxide exchange of developing avocado (Persea americana Mill.) fruit.
AB  - Net efflux of CO(2) from attached avocado (Persea americana Mill.) fruit was
      measured periodically from three weeks after anthesis to fruit maturity. Net
      CO(2) exchange was determined in daylight (light respiration, R(l)) at a
      photosynthetic photon flux (PPF) greater than 600 micromol m(-1) s(-1), and in
      the dark (dark respiration, R(d)). Dark respiration and R(l) were highest during
      the early cell division stage of fruit growth (about 25 and 22 nmol CO(2) g(dw) (
      1) s(-1), respectively) and decreased gradually until fruit maturity to about 1
      and 0.5 nmol CO(2) nmol CO(2) g(dw) (-1) s(-1), respectively. Fruit
      photosynthesis, calculated from the difference between R(d) and R(l), ranged from
      0.5 to 3.1 nmol CO(2) g(dw) (-1) s(-1). Net rate of CO(2) assimilation on a fruit
      dry weight basis was highest during the early stages of fruit growth and reached
      the lowest rate at fruit maturity. Net rate of CO(2) assimilation of fruit
      exposed to light was 0.4 to 2.5% of that for fully expanded leaves. Although the
      relative amount of carbon assimilated by the fruit was small compared with the
      total amount of carbon assimilated by the leaves, the data indicate that avocado
      fruit contribute to their own carbon requirement by means of CO(2) assimilated in
      the light.

PMID- 14969970
TI  - Limits of tolerance to high temperatures causing direct and indirect damage to
      black spruce.
AB  - The heat tolerance of actively growing 13-15-week-old black spruce (Picea mariana
      (Mill.) B.S.P.) was determined by exposing seedlings to temperatures of 40 to 60
      degrees C for durations of 5 seconds to 3 hours by direct immersion in a hot
      water bath. Direct and indirect heat damage to needles were differentiated by
      assessing damage 5 minutes (direct) and 3 weeks (indirect) after exposure to high
      temperature. Both direct and indirect damage increased exponentially with the
      duration of exposure to high temperatures. However, indirect damage occurred at
      lower temperatures and with shorter periods of exposure than direct damage.
      Arrhenius plots of length of exposure versus exposure temperature revealed that
      the energy of activation for indirect damage was 384 kJ mol(-1), 36% higher than
      for direct damage. Both direct and indirect damage were less in seedlings
      preconditioned by a heat shock treatment (3 hours of exposure to an air
      temperature of 38 degrees C on each of 6 days prior to immersion in the water
      bath). Preconditioned seedlings withstood higher temperatures and longer
      durations of high temperature exposure than seedlings not preconditioned by heat
      shock.

PMID- 14969971
TI  - Canopy photosynthesis and respiration of kiwifruit (Actinidia deliciosa var.
      deliciosa) vines growing in the field.
AB  - Net CO(2) assimilation (A) for canopies of kiwifruit (Actinidia deliciosa var.
      deliciosa) vines enclosed in a whole-canopy cuvette was measured continuously for
      three periods of 15-20 days during late summer, near Hamilton, New Zealand
      (latitude 38.2 degrees S). Canopy A showed an asymptotic response to incident
      radiation (PAR), saturating at about 1300 micromol m(-2) s(-1) for one vine and
      about 800 micromol m(-2) s(-1) for two other vines. Radiation interception at low
      solar angles and low leaf area apparently limited the response of A to PAR.
      Radiation saturated rates of A were 25-30 micromol CO(2) m(-2) s(-1) for one
      vine, and 12-18 micromol CO(2) m(-2) s(-1) for two other vines. At any PAR,
      canopy A was often lower in the afternoon than in the morning. Canopy respiration
      averaged 8.9 micromol CO(2) m(-2) s(-1) at 12 degrees C, but increased only 24
      34% over the range 7-17 degrees C. Net daily C gains for the whole canopy,
      calculated as the temporal integral of A, ranged from -0.8 g C m(-2) for a cloudy
      day (PAR </= 450 micromol m(-2) s(-1)) to 6.2 g C m(-2) for a day with
      intermittent cloud. Measurements of gas exchange for single leaves in a leaf
      cuvette were used to examine the basis of the whole-canopy responses to
      environmental variables. Partial stomatal closure due to water stress apparently
      contributed to the afternoon depressions in A, although non-stomatal limitations
      may also have been involved.

PMID- 14969972
TI  - Ecophysiological and morphological responses to shade and drought in two
      contrasting ecotypes of Prunus serotina.
AB  - Photosynthesis (A), water relations and stomatal reactivity during drought, and
      leaf morphology were evaluated on 2-year-old, sun- and shade-grown Prunus
      serotina Ehrh. seedlings of a mesic Pennsylvania seed source and a more xeric
      Wisconsin source. Wisconsin plants maintained higher A and leaf conductance
      (g(wv)) than Pennsylvania plants during the entire drought under sun conditions,
      and during the mid stages of drought under shade conditions. Compared to shade
      plants, sun plants of both sources exhibited a more rapid decrease in A or %
      A(max) with decreasing leaf water potential (Psi). Tissue water relations
      parameters were generally not significantly different between seed sources.
      However, osmotic potentials were lower in sun than shade plants under well
      watered conditions. Following drought, shade plants, but not sun plants,
      exhibited significant osmotic adjustment. Sun leaves had greater thickness,
      specific mass, area and stomatal density and lower guard cell length than shade
      leaves in one or both sources. Wisconsin sun leaves were seemingly more
      xerophytic with greater thickness, specific mass, and guard cell length than
      Pennsylvania sun leaves. No source differences in leaf structure were exhibited
      in shade plants. Stomatal reactivity to sun-shade cycles was similar between
      ecotypes. However, well-watered and droughted plants differed in stomatal
      reactivity within and between multiple sun-shade cycles. The observed ecotypic
      and phenotypic variations in ecophysiology and morphology are consistent with the
      ability of Prunus serotina to survive in greatly contrasting environments.

PMID- 14969973
TI  - Effects of acidity and detergent on in vitro pollen germination and tube growth
      in forest tree species.
AB  - The presence of 1 to 3 mg 1(-1) sodium dodecylbenzensulfonate detergent, or a
      growth medium pH of 4.0-5.0, inhibited pollen germination and pollen tube
      elongation more in broad-leaved trees than in conifers. In the broad-leaved
      species, pollen germination and pollen tube elongation showed similar
      sensitivities to detergent and acidity, whereas in the conifers, pollen tube
      elongation was more sensitive than pollen germination to detergent and acidity.
      Although the germination percentage was low, conifer pollen germinated in the
      presence of detergent concentrations up to 15 mg l(-1) and at acidities as low as
      pH 2.5 or 3.0. Pollen germination of most broad-leaved species was completely
      inhibited in the presence of detergent concentrations of more than 3-5 mg l(-1);
      the only exceptions were some entomophilous species (e.g., Salix caprea L.) in
      which the ability of the pollen to germinate in high pollutant concentrations
      could be related to the presence of tryphyne.

PMID- 14969974
TI  - Radial velocity profiles of water flow in trunks of Norway spruce and oak and the
      response of spruce to severing.
AB  - Trunk-tissue heat balance, volumetric and staining methods were used to study
      xylem water flow rates and pathways in mature Norway spruce (Picea abies (L.)
      Karst.) and pedunculate oak (Quercus robur L.) trees. The radial profile of flow
      velocity was confirmed to be symmetrical in spruce, i.e., maximum flow velocity
      was in the center of the conducting xylem and tailed with low amplitude (about 30
      cm h(-1)) in the direction of the cambium and heartwood. Variability around the
      trunk was high. In contrast, in oak, the radial profile of flow velocity was
      highly asymmetrical, reaching a peak of about 45 m h(-1) in the youngest growth
      ring and tailing centripetally for about 10 rings, but variability around the
      trunk was less, under non-limiting soil water conditions, than in spruce. In
      spruce, the flow rate increased abruptly within seconds when the tree was severed
      while immersed in water, and then decreased gradually, showing significant root
      resistance. We conclude that water flow through an absorbing cut surface differs
      from the flow higher in a tree trunk because of the presence of hydraulic
      capacitances in the conductive pathways. The staining technique always yielded
      higher estimates of flow velocity than the non-destructive tree-trunk heat
      balance method.

PMID- 14969975
TI  - Pressure-volume analysis of tissue water relations parameters for individual
      fascicles of loblolly pine (Pinus taeda L.).
AB  - A technique was tested for obtaining water relations parameters from individual
      fascicles of loblolly pine needles by the pressure-volume curve method.
      Comparisons were made between parameters derived from (1) individual fascicles
      that were rehydrated in a pressure chamber after being removed from the shoot and
      (2) fascicles that were rehydrated on the shoot. Estimates of tissue osmotic
      potential for needles rehydrated by the two methods were significantly different
      for needles from terminal shoots, but not significantly different for needles
      from lateral shoots. Similarly, a significant difference in the estimated tissue
      elasticity at zero water potential was noted for needles on terminal shoots, but
      not for those on lateral shoots. It is suggested that differences due to
      rehydration method are related to the duration of the rehydration period and not
      the choice of technique. The use of fascicles of needles, rehydrated after
      detachment, allows repeated estimation of the tissue water relations of a single
      conifer shoot.

PMID- 14969976
TI  - Carbon dioxide efflux from roots of calamodin and apple.
AB  - The specific rate of CO(2) efflux (respiration) from roots of intact fruiting
      calamodin plants (Citrus madurensis Lour.) showed no diel trend, and did not
      respond significantly to short-term (2 day) changes in shoot irradiance. Mean
      root respiration rate was about 8.4 nmol CO(2) g(-1) s(-1) at 20 degrees C, and
      increased with temperature with a Q(10) of about 2. In calamodin plants, the
      proportion of total root length that was white averaged 6.0 mm m(-1). Respiration
      of roots of apple plants (Malus domestica Borkh.), planted in spring as
      rootstocks and grown at high irradiance and N supply, declined from about 5.3 to
      2.8 nmol CO(2) g(-1) s(-1) between 46 and 138 days after bud burst. At 50%
      irradiance, root respiration was reduced more than 25% at 46 and 92 days after
      bud burst, but was not significantly affected later in the season. Reducing shoot
      irradiance reduced the proportion of total root length that was white, e.g., from
      217 to 146 mm m(-1) at 46 days after bud burst. For plants previously grown at
      low irradiance, increasing shoot irradiance for 6 days increased the rate of root
      respiration by 5 to 10%. For plants previously grown at high irradiance, reducing
      shoot irradiance for 6 days reduced root respiration by about 20% early in the
      season, but had no significant effect later in the season. For plants grown with
      low-N supply (5% of the high-N), root respiration was reduced early in the
      season, but was not significantly affected later. Reducing the N supply increased
      slightly the proportion of total root length that was white. For plants
      previously grown with low-N, increasing the N supply for 6 days reduced further
      the rate of root respiration. For plants previously grown with high-N, reducing
      the N supply for 6 days did not significantly affect the rate of root
      respiration. Specific respiration rates of root systems excised from mature trees
      growing outdoors peaked in June, at about 2.4 nmol CO(2) g(-1) s(-1), and then
      declined for the remainder of the growing season.

PMID- 14969977
TI  - Ex vitro photosynthetic activity in plantlets of tissue-cultured Douglas-fir.
AB  - Plantlets of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) had lower rates
      of net CO(2) uptake and higher rates of root respiration than greenhouse-grown
      seedlings. They also had a lower photosynthetic efficiency at high photosynthetic
      photon flux density, and exhibited significant depression of CO(2) uptake under
      water stress. The ability of plantlets to utilize high irradiance and to
      photosynthesize under conditions of water stress was enhanced by the presence of
      many roots. Carbon dioxide uptake rate increased with increasing root number, and
      decreased as the needle surface area/root surface area ratio decreased. High root
      number, low needle surface area/root surface area ratio, and elongated roots were
      associated with low apparent rates of shoot and root respiration.

PMID- 14969978
TI  - Loss of hydraulic conductivity due to water stress in intact juveniles of Quercus
      rubra and Populus deltoides.
AB  - Despite many studies of the percent loss of hydraulic conductivity in excised
      branches, there is doubt as to whether cutting stems in air introduces unnatural
      embolism into the xylem at the cut surface. To address this question, hydraulic
      conductivity was measured in seedlings of northern red oak (Quercus rubra L.) and
      rooted scions of eastern cottonwood (Populus deltoides Bartr. ex Marsh.) that had
      been droughted in pots. Results indicate that in situ dehydration produced a very
      similar vulnerability curve (% loss of conductivity versus water potential) to
      those previously obtained by bench-top dehydration of excised branches of eastern
      cottonwood and red oak. In eastern cottonwood cuttings, conductivity loss
      increased sharply below water potentials of -1.0 MPa, with 100% loss of
      conductivity occurring by -2.0 MPa, whereas conductivity loss in red oak
      seedlings was more gradual, i.e., increasing below -1.5 MPa and sustaining 100%
      loss of conductivity by about -4.0 MPa.

PMID- 14969979
TI  - Comparison of methods for estimating surface area of water-stressed and fully
      hydrated pine needle segments for gas exchange analysis.
AB  - A nondestructive technique for repeatedly estimating total surface area of water
      stressed pine (Pinus taeda L.) fascicle segments was evaluated. Fascicle radius
      was measured with a digital caliper and needle surface area calculated on the
      assumption that the needles were segments of a cylinder. High correlations (r >/=
      0.94) were found between surface area estimated in this way and surface area
      calculated (a) from needle displacement, also on the assumption that needles are
      segments of a cylinder, and (b) from needle dry weight using a regression between
      dry weight and surface area estimated from needle displacement. The caliper
      radius method gave slightly lower estimates of surface area than the other
      methods. However, differences among surface area estimates made with the three
      methods and between estimates made on water-stressed and fully hydrated needles
      were small relative to variances of leaf gas exchange measurements.

PMID- 14969980
TI  - Effects of root temperature on growth and photosynthesis in conifer seedlings
      during shoot elongation.
AB  - Growth and gas exchange characteristics were studied in pine (Pinus sylvestris
      L.) and spruce (Picea abies Karst.) seedlings grown in hydroponic culture in the
      presence of N (50 mg l(-1)) and transferred at the start of their second growing
      season to tap water at 5, 8, 12, 16 or 20 degrees C (air temperature between 18
      20 degrees C) for 3 weeks (pine) or 5 weeks (spruce). Root growth of both species
      was completely inhibited at root temperatures of 5 and 8 degrees C, but increased
      almost exponentially as root temperature increased. Shoot growth was maximal at
      12 degrees C in both pine and spruce and decreased at low root temperatures. In
      both species, CO(2) uptake was decreased at low root temperatures and appeared to
      be influenced by the pattern of nitrogen retranslocation. In pine seedlings, as
      root temperature increased, an increasing proportion of the total nitrogen pool
      was retranslocated to the new shoot, whereas in spruce seedlings nitrogen was
      retranslocated to the roots. Differences in the retranslocation of nitrogen in
      the two species were reflected in the amount of soluble protein in needles, which
      at the end of the experiment increased with increasing root temperature in pine,
      but decreased in spruce. Our data suggest that in spruce, but not pine, CO(2)
      uptake was limited by the amount of Rubisco.

PMID- 14969981
TI  - Hydraulic conductance and soil water potential at the soil-root interface of
      Pinus pinaster seedlings inoculated with different dikaryons of Pisolithus sp.
AB  - Seedlings of maritime pine (Pinus pinaster Ait.) were inoculated with different
      dikaryons of Pisolithus sp. from South Africa to determine the influence of
      extension of the extramatrical phase and diameter of the mycelial strands on
      water relations parameters including xylem water potential (Psi(x)), soil water
      potential at the soil-root interface (Psi(s)) and hydraulic conductance (L(p))
      during and after a period of water stress. Seedlings inoculated with dikaryons
      having an extensive extramatrical phase and large diameter mycelial strands
      showed higher Psi(s) (-2 MPa) during severe water stress than seedlings
      inoculated with dikaryons producing fine hyphae and sparse extramatrical phases (
      3.8 MPa). Seedlings inoculated with strand-forming dikaryons recovered faster
      from water stress than did non-inoculated seedlings or seedlings inoculated with
      non-strand-forming dikaryons. Architectural aspects of the extramatrical phase,
      including the presence of large diameter mycelial strands or fine hyphae,
      influenced the soil-root contact and the water relations of an inoculated host
      plant. When water stress was not limiting, the architecture of the extramatrical
      phase did not have a large effect on Psi(s). It is suggested that the
      architecture of the extramatrical phase influences the resistance to water flow
      through the soil-root interface and that large mycelial strands increase the
      water flow by bridging the gap between the soil and the root. These changes in
      physiology indicate that dikaryons can improve the survival of Pinus pinaster
      under dry conditions.

PMID- 14969982
TI  - Root growth and carbohydrate responses in bearing citrus trees following partial
      canopy removal.
AB  - In August, eight 4-m tall citrus trees were pruned by removing the top third of
      their canopy. Eight unpruned trees served as controls. Root growth, which was
      examined nondestructively with minirhizotrons over a four-month period, tended to
      be less in the pruned than unpruned trees seven days after pruning and this
      difference was significant (P < 0.05) from 14 to 49 days after pruning. Total
      reducing and ketone sugars (includes free fructose, sucrose and fructans) in the
      fine roots were less in pruned than unpruned trees 20 days after pruning, but not
      thereafter. By 30 days after pruning, at least 20% of the roots of the pruned
      trees at a soil depth of 9 to 35 cm apparently died. By 63 days after pruning,
      root length density had recovered to that of the unpruned trees, although starch
      reserves were 18% less in the fine roots of pruned than unpruned trees at this
      time. Nine to eleven months after pruning (May to July), total biomass of leaves
      and fine roots to a depth of 1 m were similar in pruned and unpruned trees.
      However, fruit biomass harvested in April from pruned trees was only 24% of that
      in the unpruned trees. In May, nonstructural carbohydrates in the fine and coarse
      roots of pruned trees were generally greater than in unpruned trees, possibly
      reflecting previous differences in fruit production.

PMID- 14969983
TI  - Influence of a high Mn supply on Norway spruce (Picea abies (L.) Karst.)
      seedlings in relation to the nitrogen source.
AB  - Effects of 3, 25, 100, 200 and 800 microM Mn on biomass and pigment, starch and
      nitrate concentrations were studied in Norway spruce (Picea abies (L.) Karst.)
      seedlings grown with either NO(3) (-) or NH(4) (+) as the sole nitrogen source.
      After 77 days of exposure to 800 microM Mn, shoot growth had ceased in about 50%
      of the seedlings independently of the N source. Despite high Mn concentrations in
      roots and shoots of the Mn-treated seedlings, no visible symptoms of Mn toxicity
      were evident. The rate of root elongation was decreased by treatment with >/= 200
      microM Mn when N was supplied as NO(3) (-), but not when it was supplied as NH(4)
      (+). This difference could be attributed to the higher Mn concentrations in root
      tips of the NO(3) (-)-grown seedlings compared with the NH(4) (+)-grown
      seedlings. In Mn-treated seedlings, the concentration of Mg, and to a lesser
      extent that of Ca, decreased. Depletion of these elements might account for the
      observed growth depression. Potassium concentrations were similar in the control
      and Mn-treated seedlings. Treatment of seedlings with 800 microM Mn for 50 days
      led to several physiological changes: starch accumulated, the concentrations of
      nitrate and phenolic compounds increased, pigment concentrations decreased, and
      in vivo nitrate reductase activity in roots was reduced.

PMID- 14969984
TI  - Effects of severe dehydration on leaf photosynthesis in Quercus petraea (Matt.)
      Liebl.: photosystem II efficiency, photochemical and nonphotochemical
      fluorescence quenching and electrolyte leakage.
AB  - Leaf disks of oak (Quercus petraea (Matt.) Liebl.) trees were subjected to rapid
      dehydration in air in the dark. Optimal photochemical efficiency of PS II
      (F(v)/F(M)), photochemical (q(P)) and nonphotochemical (q(NP)) quenchings of
      chlorophyll a fluorescence, and relative conductivity (C(r)) of leaf disk
      diffusate were measured in leaf disks with different water deficits (D). No
      effect of dehydration was detected before D reached values above 0.30. When D
      increased from 0.30 to 0.50, q(NP) increased without any change in q(P), which
      may indicate that thermal deexcitation of PS II increased, allowing reduced
      photochemical activity and maintenance of a large pool of oxidized primary
      acceptors (QA), although carbon reduction was impaired. Large changes in electron
      transport chain activity, leading to decreases in both q(P) and q(NP), appeared
      only in leaf disks subjected to severe water deficits (D > 0.60) and were
      correlated with a modification of membrane structure. However, stability of
      F(v)/F(M) indicated that the functional integrity of PS II was not altered until
      D reached values above 0.75. We conclude that the photosynthetic apparatus of Q.
      petraea is rather insensitive to leaf dehydration per se during drought under
      natural conditions.

PMID- 14969985
TI  - Root aeration in wetland trees by pressurized gas transport.
AB  - Tracer gas studies and oxygen uptake measurements have shown that pressurized gas
      transport improves oxygen supply to roots in the wetland tree species Taxodium
      distichum L. Rich. (Taxodiaceae), Betula pubescens J.F. Ehrh. (Betulaceae), and
      Populus tremula L. (Salicaceae), but not in Acer pseudoplatanus L. and Ilex
      aquifolium L., which are found in drier habitats. In the deciduous tree species
      Betula pubescens and Populus tremula, pressurized gas transport was most evident
      during the resting period, which is characterized by soil anoxia following
      waterlogging of the natural habitat. Because pressurized gas transport is found
      in species of distantly related families, we hypothesize that it helps wetland
      species survive the initial period of soil flooding before acclimation to
      waterlogging cccurs.

PMID- 14969986
TI  - Effects of compaction and simulated root channels in the subsoil on root
      development, water uptake and growth of radiata pine.
AB  - Effects of subsoil compaction and simulated root channels (perforations) through
      the compacted layer on root growth, water uptake, foliar nutrient concentration
      and growth of radiata pine (Pinus radiata D. Don) were studied in a field
      experiment where a range of treatments were applied in reconstituted soil
      profiles. Subsoil compaction adversely affected root penetration in deeper parts
      of the soil and consequently caused greater water stress in trees. However, the
      effect of compaction was largely overcome when the subsoil was perforated to
      render 0.2% of the soil volume into vertical channels. Roots showed a remarkable
      ability to reach the points of low penetration strength and to travel through
      them to deeper parts of the profile. Perforations through compacted soil layers
      at a relatively low frequency may be a practical solution to allow root
      development into deeper parts of the soil and allow greater soil water
      exploration by roots.

PMID- 14969987
TI  - Micronutrient distribution in 16-year-old maritime pine.
AB  - Concentrations and contents of the micronutrients Fe, Mn, Zn, Cu, and B were
      measured in various tree compartments of a 16-year-old stand of maritime pine
      (Pinus pinaster Soland in Ait.). The micronutrients were actively redistributed
      within the tree. The longer-lived aerial tissues, trunks and branches,
      constituted the major micronutrient reservoirs, with the exception of manganese
      which accumulated in the needles.

PMID- 14969988
TI  - Effect of ABA on freezing resistance of Betula papyrifera and Alnus incana woody
      plant cell suspensions.
AB  - Treatment of birch (Betula papyrifera Marsh) and alder (Alnus incana (L.) Moench)
      cell suspension cultures with ABA increased the freezing resistance of the cells.
      After 7 days of treatment with 10(-5) M ABA, birch cells grown at 23 and 4
      degrees C attained an LT(50) of -16.9 and -14.1 degrees C, respectively, whereas
      control cells had an LT(50) of -9.1 degrees C. In alder cell suspensions,
      treatment with 10(-5) M ABA at 23 degrees C induced a small increase in freezing
      resistance from -7.3 to -10.8 degrees C. Exposure to 4 degrees C alone did not
      induce a significant increase in hardiness in birch cell suspensions. Addition of
      10(-5) M ABA to the medium inhibited fresh weight increase over 10 days of 3-g
      inocula of birch and alder by 70 and 52%, respectively. With the same
      concentration of ABA in the medium we found different intracellular ABA
      concentrations in 3- and 6-g inocula. We conclude that the concentration of ABA
      in the medium does not reflect the intracellular concentration of tissue
      cultures, and that cultural conditions may influence ABA accumulation by cell
      cultures.

PMID- 14969989
TI  - An analysis of sap flow in mountain ash (Eucalyptus regnans) forests of different
      age.
AB  - Diurnal measurements of sap velocity were made in 50-, 90-, 150- and 230-year-old
      mountain ash (Eucalyptus regnans F. Muell.) forests in the North Maroondah
      catchment (southeast Australia) over the periods January 8, 1990 to April 4, 1990
      and October 29, 1990 to April 16, 1991. Over the two periods, daily mean sap
      velocities for the four forests, in order of increasing age, were 11.5, 11.4, 9.9
      and 11.8 cm h(-1) respectively. Daily mean sap velocity did not differ
      significantly among the 50-, 90- and 230-year-old plots. However, in the 150-year
      old trees it was significantly smaller by an average of 14%. Sap velocity varied
      diurnally and also between positions within individual trees and among trees both
      within and between stands. Despite this variability, the sampling intensity and
      duration were sufficient to establish that behavior was highly correlated among
      individuals within plots. There was a significant decline with age in the
      overstory sapwood conducting area of these forests. In order of increasing age,
      the values were 6.7, 6.1, 4.2 and 4.0 m(-2) ha(-1), respectively. When combined
      with daily mean sap velocity, these data allowed the calculation of overstory
      water use. Over the experimental period, water use of the overstory decreased
      with age ranging, on average, from 1.86 mm day(-1) for the 50-year-old plot to
      0.81 mm day(-1) for the 230-year-old plot. Mean daily water use for the two
      intermediate-aged forests was 1.67 and 1.00 mm day(-1), respectively. Annual
      water use decreased with forest age from 679 mm for the 50-year-old stand to 296
      mm for the 230-year-old stand. This difference corresponds to 3.8 x 10(3) m(3)
      ha(-1). The annual water use of the intermediate-aged stands was 610 and 365 mm
      for the 90- and 150-year-old stands, respectively.

PMID- 14969990
TI  - Vascular tissue anatomy of Norway spruce needles and twigs in relation to
      magnesium deficiency.
AB  - Vascular tissues of needles and twigs of Norway spruce with low foliar magnesium
      concentrations were examined by light microscopy. Observations were made on
      samples from (1) apparently healthy trees, (2) trees exhibiting progressive
      symptoms of decline, including the yellowing and fall of needles and the death of
      twigs and branches in the subapical canopy, and (3) trees recovering from
      symptoms of decline after fertilization with magnesium sulfate. Abnormalities in
      cambium and phloem anatomy, which were apparent in 2-year-old needles of
      declining trees, were seen only in needles at least 4 years old in healthy trees,
      suggesting that needles of declining trees are susceptible to precocious aging.
      Abnormalities in xylem anatomy were observed in needles 3 years or more in age in
      declining trees, but were never seen in needles of healthy trees. Over time,
      anatomical abnormalities in declining trees were seen in progressively younger
      twigs, which may explain the acropetal development of decline symptoms. After
      fertilization with magnesium sulfate, normal phloem and xylem were observed in
      the newly formed tissues.

PMID- 14969991
TI  - Carbohydrate reserve accumulation and depletion in Engelmann spruce (Picea
      engelmannii Parry): effects of cold storage and pre-storage CO(2) enrichment.
AB  - The effects of pre-storage CO(2) enrichment on growth, non-structural
      carbohydrates and post-storage root growth potential of Engelmann spruce (Picea
      engelmannii Parry) seedlings were studied. Seedlings were grown from seed for 202
      days in growth chambers with ambient (340 micro l l(-1)) or CO(2) enriched (1000
      micro l l(-1)) air. Some seedlings were transferred between CO(2) treatments at
      60 and 120 days. Photoperiod was reduced at 100 days to induce bud set and
      temperature was reduced at 180 days to promote frost hardiness development for
      storage at -5 degrees C for 2 or 4 months. Stored seedlings were planted in a
      growth chamber after thawing for one week at +5 degrees C. At 80, 120, 140 and
      202 days, and at each planting time after storage, seedlings were harvested for
      growth measurements and analysis of starch and soluble sugar concentrations.
      Planted seedlings were assessed for bud break every two days and new roots > 5 mm
      long were counted after four weeks. Carbon dioxide enrichment increased root
      collar diameter and almost doubled seedling biomass, with the most obvious
      effects occurring after bud set. Stem height was affected only slightly and
      shoot/root ratios were not affected at all. Carbon dioxide enrichment increased
      the rate of reserve carbohydrate accumulation, but did not influence the final
      concentration attained before storage (accounting for 32% of seedling dry
      weight). Needles were the major storage organ for soluble sugars, whereas roots
      were the major storage organ for starch. Soluble sugars were not strongly
      affected by two or four months of storage, but starch was reduced by more than
      50% in all plant parts. None of the CO(2) treatments had an impact on bud break
      or root growth potential.

PMID- 14969992
TI  - Polyamines in embryogenic cultures of Norway spruce (Picea abies) and red spruce
      (Picea rubens).
AB  - Embryogenic cultures of red spruce (Picea rubens Sarg.) and Norway spruce (Picea
      abies (L.) Karst.) were initiated from dissected mature zygotic embryos. The
      tissues were grown on either proliferation medium or maturation medium. On
      proliferation medium, the embryogenic tissue continued to produce early stage
      somatic embryos (organized meristems attached to elongated, suspensor-like
      cells), whereas on maturation medium fully mature embryos developed from the
      embryonic tissue. Analysis of polyamines in tissues grown on these two media
      showed that: (1) both putrescine and spermidine concentrations were always higher
      in cultures grown on proliferation medium than in cultures grown on maturation
      medium; (2) in both species, spermidine concentrations declined with time in the
      tissues grown on maturation medium; and (3) spermine was present in only minute
      quantities and showed only a small change with time. The presence of
      difluoromethylornithine in the culture medium had little effect on polyamine
      concentration, whereas the presence of difluoromethylarginine caused a decrease
      in putrescine concentrations in both red spruce and Norway spruce tissues grown
      on proliferation medium or maturation medium.

PMID- 14969993
TI  - Seasonal variations in soluble sugars and starch within woody stems of Cornus
      sericea L.
AB  - Carbohydrate composition changed seasonally in red osier dogwood (Cornus sericea
      L.) stem tissues. Starch concentration was highest in fall and decreased to a
      minimum in midwinter. Coincident with the breakdown of starch in fall, there was
      an increase in the concentrations of soluble sugars. Soluble sugars were present
      in highest concentrations in midwinter. Glucose, fructose, sucrose, and raffinose
      were the predominant soluble sugars present in both bark and wood tissues. In
      early spring, the soluble sugar concentration decreased and the concentration of
      starch increased. The seasonal interchange between sugars and starch did not
      simply reflect a general quantitative shift in the balance between sugars and
      starch because qualitative changes in soluble sugars were also noted. The most
      striking changes involved the trisaccharide raffinose. Raffinose was barely
      detectable in summer and early fall, but increased to one fifth and one third of
      the total soluble sugars in January samples of bark and wood tissues,
      respectively. The potential physiological role of raffinose in overwintering red
      osier dogwood tissue is discussed.

PMID- 14969994
TI  - Effects of elevated carbon dioxide and drought on the growth and physiology of
      clonal Sitka spruce plants (Picea sitchensis (Bong.) Carr.).
AB  - Two-year-old Sitka spruce (Picea sitchensis (Bong.) Carr.) plants from four
      clones were grown in naturally lit growth chambers for 6 months at either ambient
      (350 ppm) or ambient + 250 ppm (600 ppm) CO(2) concentration. Plants were grown
      in large boxes filled with peat, in a system that allowed the roots of individual
      plants to be harvested easily at the end of the growing season. Half of the boxes
      were kept well watered and half were allowed to dry out slowly over the summer.
      Plants growing in elevated CO(2) showed a 6.9% increase in mean relative growth
      rate compared to controls in the drought treatment and a 9.8% increase compared
      to controls in the well-watered treatment, though there was considerable
      variation in response among the different clones and water treatments. Rates of
      net CO(2) assimilation were higher and stomatal conductances were lower in plants
      grown in elevated CO(2) than in ambient CO(2) in both the well-watered and
      drought treatments. Both of these factors contributed to the doubling of
      instantaneous water use efficiency. The partitioning of biomass to roots was
      unaffected by elevated CO(2), but the ratio of needle mass/stems + branches mass
      decreased. Together with reduced stomatal conductance, this probably caused the
      observed increases in xylem pressure potentials with elevated CO(2).

PMID- 14969995
TI  - Floral biology and breeding behavior in the bamboo Dendrocalamus strictus Nees.
AB  - Floral biology and breeding behavior were studied in the bamboo Dendrocalamus
      strictus Nees. The inflorescence in this species is a large branching panicle.
      Fertile florets are intermixed with smaller sterile ones. There are six stamens.
      The ovary is stipitate and turbinate. The style is long and the stigma is bifid
      and plumose. Dendrocalamus strictus is typically dichogamous and protogynous. The
      gynoecium matures 3-4 days before the androecium, effectively preventing self
      pollination. Flower bloom, which took place over a period of 2 to 3 h, was
      dependent on air temperature and only occurred between 0600 and 1300 h.
      Dendrocalamus strictus is anemophilous. Flowers in the male phase were visited by
      insects. These insects completely neglected the flowers at the female phase. The
      insects fed on the pollen and were not pollen vectors. When wind was excluded by
      enclosing the inflorescences in bags there was no seed set, indicating that cross
      pollination by wind is necessary for fertilization and that parthenocarpy and
      apomixis are not occurring in this species. Pollen fertility was about 98% as
      indicated by staining fresh pollen at the time of anther dehiscence and pollen
      release with Alexander's stain (Alexander 1969). When placed on a modified
      Brewbaker-Kwak medium containing 1% glucose, the pollen grains germinated well,
      and the pollen tubes grew to 15-20 times the diameter of mature pollen grains.
      Although profound protogyny has its disadvantages in times of sporadic flowering,
      it can be useful in breeding programs because it eliminates the need for
      emasculation.

PMID- 14969996
TI  - Seasonal changes in the axial distribution of peroxidase activity in the xylem
      sap of beech (Fagus sylvatica L.) trees.
AB  - Xylem sap was collected from trunk segments of adult beech (Fagus sylvatica L.)
      trees by water displacement. Peroxidase activity was analyzed in xylem saps
      collected in different phases of the yearly growth cycle and from different
      heights up the trunks (up to 14 m). The xylem saps contained two major peroxidase
      isozymes with acidic isoelectric points of 4.1 and 4.6, respectively. Mean
      peroxidase activity was low during the emergence of the new leaves and high in
      summer and in winter. In the cold season, peroxidase activity decreased from the
      stem base to the top, whereas significant gradients were not observed during the
      vegetative period.

PMID- 14969997
TI  - Molecular mechanisms of pulmonary peptidomimetic drug and peptide transport.
AB  - The aerosolic administration of peptidomimetic drugs could play a major role in
      the future treatment of various pulmonary and systemic diseases, because rational
      drug design offers the potential to specifically generate compounds that are
      transported efficiently into the epithelium by distinct carrier proteins such as
      the peptide transporters. From the two presently known peptide transporters,
      PEPT1 and PEPT2, which have been cloned from human tissues, the high-affinity
      transporter PEPT2 is expressed in the respiratory tract epithelium. The
      transporter is an integral membrane protein with 12 membrane-spanning domains and
      mediates electrogenic uphill peptide and peptidomimetic drug transport by
      coupling of substrate translocation to a transmembrane electrochemical proton
      gradient serving as driving force. In human airways, PEPT2 is localized to
      bronchial epithelium and alveolar type II pneumocytes, and transport studies
      revealed that both peptides and peptidomimetic drugs such as antibiotic,
      antiviral, and antineoplastic drugs are carried by the system. PEPT2 is also
      responsible for the transport of delta-aminolevulinic acid, which is used for
      photodynamic therapy and the diagnostics of pulmonary neoplasms. Based on the
      recent progress in understanding the structural requirements for substrate
      binding and transport, PEPT2 becomes a target for a rational drug design that may
      lead to a new generation of respiratory drugs and prodrugs that can be delivered
      to the airways via the peptide transporter.

PMID- 14969998
TI  - Effect of renal denervation on dynamic autoregulation of renal blood flow.
AB  - Vasoconstrictor intensities of renal sympathetic nerve stimulation elevate the
      renal arterial pressure threshold for steady-state stepwise autoregulation of
      renal blood flow. This study examined the tonic effect of basal renal sympathetic
      nerve activity on dynamic autoregulation of renal blood flow in rats with normal
      (Sprague-Dawley and Wistar-Kyoto) and increased levels of renal sympathetic nerve
      activity (congestive heart failure and spontaneously hypertensive rats). Steady
      state values of arterial pressure and renal blood flow before and after acute
      renal denervation were subjected to transfer function analysis. Renal denervation
      increased basal renal blood flow in congestive heart failure (+35 +/- 3%) and
      spontaneously hypertensive rats (+21 +/- 3%) but not in Sprague-Dawley and Wistar
      Kyoto rats. Renal denervation significantly decreased transfer function gain
      (i.e., improved autoregulation of renal blood flow) and increased coherence only
      in spontaneously hypertensive rats. Thus vasoconstrictor intensities of renal
      sympathetic nerve activity impaired the dynamic autoregulatory adjustments of the
      renal vasculature to oscillations in arterial pressure. Renal denervation
      increased renal blood flow variability in spontaneously hypertensive rats and
      congestive heart failure rats. The contribution of vasoconstrictor intensities of
      basal renal sympathetic nerve activity to limiting renal blood flow variability
      may be important in the stabilization of glomerular filtration rate.

PMID- 14969999
TI  - Mutations in the extracellular loop of alpha-rENaC alter sensitivity to amiloride
      and reactive species.
AB  - We studied the effects of two mutations of the extracellular loop of the alpha
      subunit of the (ENaC) on amiloride-sensitive current in Xenopus laevis oocytes
      and the inhibition of this current by 3-morpholinosydnonimine (SIN-1). Injection
      of oocytes with wild-type (wt) alpha-,beta-,gamma-rENaC cRNA (8.3 ng/subunit)
      resulted 48-72 h later in inward Na(+) currents (-5.5 +/- 0.8 microA; means +/-
      SE at -100 mV; n = 21), which were completely inhibited by amiloride. Oocytes
      injected with either alpha(Y279A)- or alpha(Y283A)- and beta-,gamma-rENaC cRNAs
      had significantly lower Na(+) currents. Furthermore, alpha(Y279A)-,beta-,gamma
      rENaC-injected oocytes had a higher K(i) for amiloride (0.54 +/- 0.97 vs. 0.10 +/
      0.04 microM; P < 0.01). Exposure of oocytes to SIN-1 (1 mM) for 5 min decreased
      both total Na(+) and amiloride-sensitive currents across wt and alpha(Y279A)- but
      not alpha(Y283A)-,beta-,gamma-rENaC. Furthermore, exposure to SIN-1 increased the
      K(i) for amiloride across wt but not alpha(Y279A)-,beta-,gamma-rENaC-injected
      oocytes. These data indicate that both tyrosines are important for proper ENaC
      function and their oxidative modifications contribute to altered ENaC function.

PMID- 14970000
TI  - A simplified method for HPLC determination of creatinine in mouse serum.
AB  - Mouse models are frequently used to study renal function. However, mouse serum
      contains chromagens that interfere with standard picric acid-based assays for
      serum creatinine. Several alternative methods exist for serum creatinine
      measurements, including assay by high-performance liquid chromatography (HPLC),
      but only one has been adapted to mouse serum. Creatinine was measured in serum by
      acetonitrile deproteinization, followed by isocratic, cation exchange HPLC. The
      HPLC method was compared with a standard alkaline picrate colorimetric assay,
      using serum from animals with low-to-moderate renal injury. Acidification of
      acetonitrile with HCl in the deproteinization step produced variable results,
      including an extra peak that interfered with integration of the creatinine peak
      or loss of the creatinine peak. Deproteinizing with acetonitrile alone resulted
      in a more reliable measurement of serum creatinine, which was validated by a
      series of known additions of creatinine standard. The HPLC assay was reproducible
      with coefficients of variation from 1.6 to 5.1%. The picric acid assay
      overestimated serum creatinine, when directly compared with the HPLC assay. The
      extent of overestimation, up to sixfold, was greatest at normal (0.1 to 0.2
      mg/dl) to moderately elevated (0.5 mg/dl) serum creatinine levels. Mouse serum
      contains substances that interfere with standard picric acid assays for
      creatinine. Our new HPLC assay can accurately detect creatinine from 5 microl of
      mouse serum. These results support the widespread adoption of HPLC to accurately
      measure serum creatinine in mouse models of renal injury.

PMID- 14970001
TI  - Defective D1-like receptor-mediated inhibition of the Cl-/HCO3- exchanger in
      immortalized SHR proximal tubular epithelial cells.
AB  - The sensitivity of the Cl(-)/HCO(3)(-) exchanger to dopamine D(1)- and D(2)-like
      receptor stimulation in immortalized renal proximal tubular epithelial cells from
      the spontaneous hypertensive rat (SHR) and Wistar-Kyoto rat (WKY) was examined.
      The activity of the Cl(-)/HCO(3)(-) exchanger (in pH U/s) in SHR cells (0.00191)
      was greater than in WKY cells (0.00126). The activity of Cl(-)/HCO(3)(-)
      exchanger was exclusively observed at the apical cell side and probably occurs
      through the SLC26A6 anion transporter that is expressed in both WKY and SHR
      cells. Stimulation of D(1)-like receptors with SKF-38393 markedly attenuated the
      HCO(3)(-)-dependent intracellular pH recovery in WKY cells but not in SHR cells.
      Stimulation of D(2)-like receptors with quinerolane did not alter Cl(-)/HCO(3)(-)
      exchanger activity in both WKY and SHR cells. The selective D(1)-like receptor
      antagonist SKF-83566 prevented the effect of SKF-38393. Both WKY and SHR cells
      responded to dibutyryl-cAMP (DBcAMP) with inhibition of the Cl(-)/HCO(3)(-)
      exchanger, and downregulation of PKA (overnight exposure to DBcAMP) abolished the
      inhibitory effect of both DBcAMP and SKF-38393 in WKY cells. Both SHR and WKY
      cells responded to forskolin with increases in the formation of cAMP. However,
      only WKY responded to SKF-38393 with increases in the formation of cAMP that was
      prevented by SKF-83566. It is concluded that WKY cells respond to D(1)-like
      dopamine receptor stimulation with inhibition of the apical Cl(-)/HCO(3)(-)
      (SLC26A6) exchanger and SHR cells have a defective D(1)-like dopamine response.

PMID- 14970002
TI  - Involvement of guanylyl cyclase and cGMP in the regulation of Mrp2-mediated
      transport in the proximal tubule.
AB  - In killifish renal proximal tubules, endothelin-1 (ET-1), acting through a
      basolateral ET(B) receptor, nitric oxide synthase (NOS), and PKC, decreases cell
      to-lumen organic anion transport mediated by the multidrug resistance protein
      isoform 2 (Mrp2). In the present study, we examined the roles of guanylyl cyclase
      and cGMP in ET signaling to Mrp2. Using confocal microscopy and quantitative
      image analysis to measure Mrp2-mediated transport of the fluorescent drug
      fluorescein methotrexate (FL-MTX), we found that oxadiazole quinoxalin (ODQ), an
      inhibitor of NO-sensitive guanylyl cyclase, blocked ET-1 signaling. ODQ was also
      effective when signaling was initiated by nephrotoxicants (gentamicin, amikacin,
      diatrizoate, HgCl(2), and CdCl(2)), which appear to stimulate ET release from the
      tubules themselves. ODQ blocked the effects of the NO donor sodium nitroprusside
      but not of the phorbol ester that activates PKC. Exposing tubules to 8-bromo-cGMP
      (8-BrcGMP), a cell-permeable cGMP analog, decreased luminal FL-MTX accumulation.
      This effect was abolished by bisindoylmaleimide (BIM), a PKC inhibitor, but not
      by N(G)-methyl-l-arginine, a NOS inhibitor. Together, these data indicate that ET
      regulation of Mrp2 involves activation of guanylyl cyclase and generation of
      cGMP. Signaling by cGMP follows NO release and precedes PKC activation.

PMID- 14970003
TI  - Altered triglyceride-rich lipoprotein production in Zucker diabetic fatty rats.
AB  - Triglyceride-rich lipoprotein (TRL) production was studied in Zucker diabetic
      fatty (ZDF) rats, a model of insulin-resistant type 2 diabetes progression. TRL
      production was measured in vivo by blocking catabolism with Triton WR-1339. Ten
      week ZDF rats are hyperinsulinemic with increased TRL production [both
      triglyceride and apolipoprotein B (apoB)]. Twenty-week ZDF rats are
      insulinopenic, and TRL production is similar to lean controls. Insulin infusion
      suppresses glucose and free fatty acids in 10- and 20-wk ZDF rats. Increased TRL
      production is not reduced by insulin in 10-wk rats; however, at 20 wk, TRL
      production is suppressed by insulin. In vitro studies with hepatocytes derived
      from 10-wk ZDF rats showed minimal insulin dose effects on apoB secretion
      compared with the response and sensitivity of hepatocytes derived from 20-wk ZDF
      and control lean rats. Hepatic sterol regulatory-binding protein (SREBP)-1c mRNA
      levels are increased at 10 wk but return to control levels at 20 wk. ApoB mRNA
      levels are similar to lean controls at 10 and 20 wk. The following two mechanisms
      for hypertriglyceridemia associated with hyperinsulinemia are suggested:
      increased TRL synthesis and loss of TRL suppression. Increased triglyceride
      production in hyperinsulinemic rats likely relates to increased expression of
      SREBP-1c, whereas increased apoB production involves posttranscriptional
      processes.

PMID- 14970004
TI  - Glucose homeostasis in abdominal obesity: hepatic hyperresponsiveness to growth
      hormone action.
AB  - It has been suggested that (abdominally) obese individuals are hypersensitive to
      growth hormone (GH) action. Because GH affects glucose metabolism, this may
      impact glucose homeostasis in abdominal obesity. Therefore, we studied the effect
      of GH on glucose metabolism in abdominally obese (OB) and normal-weight (NW)
      premenopausal women. A 1-h intravenous infusion of GH or placebo was randomly
      administered to six NW [body mass index (BMI) 21.1 +/- 1.9 kg/m(2)] and six OB
      (BMI 35.5 +/- 1.5 kg/m(2)) women in a crossover design. Insulin, glucagon, and GH
      secretion were suppressed by concomitant infusion of somatostatin. Glucose
      kinetics were measured using a 10-h infusion of [6,6-(2)H(2)]glucose. In both
      groups, similar physiological GH peaks were reached by infusion of GH. GH
      strongly stimulated endogenous glucose production (EGP) in both groups. The
      percent increase was significantly greater in OB than in NW women (29.8 +/- 11.3
      vs. 13.3 +/- 7.4%, P = 0.014). Accordingly, GH responsiveness, defined as the
      maximum response of EGP per unit GH, was increased in OB vs. NW subjects (6.0 +/-
      2.1 vs. 2.2 +/- 1.5 micromol.min(-1).mU(-1).l(-1), P = 0.006). These results
      suggest that the liver is hyperresponsive to GH action in abdominally obese
      women. The role of the somatotropic ensemble in the control of glucose
      homeostasis in abdominal obesity is discussed.

PMID- 14970005
TI  - Total branched-chain amino acids requirement in patients with maple syrup urine
      disease by use of indicator amino acid oxidation with L-[1-13C]phenylalanine.
AB  - Maple syrup urine disease (MSUD) is an autosomal recessive disorder caused by
      defects in the mitochondrial multienzyme complex branched-chain alpha-keto acid
      dehydrogenase (BCKD; EC 1.2.4.4), responsible for the oxidative decarboxylation
      of the branched-chain ketoacids (BCKA) derived from the branched-chain amino
      acids (BCAA) leucine, valine, and isoleucine. Deficiency of the enzyme results in
      increased concentrations of the BCAA and BCKA in body cells and fluids. The
      treatment of the disease is aimed at keeping the concentration of BCAA below the
      toxic concentrations, primarily by dietary restriction of BCAA intake. The
      objective of this study was to determine the total BCAA requirements of patients
      with classical MSUD caused by marked deficiency of BCKD by use of the indicator
      amino acid oxidation (IAAO) technique. Five MSUD patients from the MSUD clinic of
      The Hospital for Sick Children participated in the study. Each was randomly
      assigned to different intakes of BCAA mixture (0, 20, 30, 50, 60, 70, 90, 110,
      and 130 mg.kg(-1).day(-1)), in which the relative proportion of BCAA was the same
      as that in egg protein. Total BCAA requirement was determined by measuring the
      oxidation of l-[1-(13)C]phenylalanine to (13)CO(2). The mean total BCAA
      requirement was estimated using a two-phase linear regression crossover analysis,
      which showed that the mean total BCAA requirement was 45 mg.kg(-1).day(-1), with
      the safe level of intake (upper 95% confidence interval) at 62 mg.kg(-1).day(-1).
      This is the first time BCAA requirements in patients with MSUD have been
      determined directly.

PMID- 14970006
TI  - Tissue-specific regulation of cytochrome c oxidase subunit expression by thyroid
      hormone.
AB  - The influence of thyroid hormone (T(3)) on respiration is partly mediated via its
      effect on the cytochrome c oxidase (COX) enzyme, a multi-subunit complex within
      the mitochondrial respiratory chain. We compared the expression of COX subunits
      I, III, Vb, and VIc and thyroid receptors (TR)alpha1 and TRbeta1 with functional
      changes in COX activity in tissues that possess high oxidative capacities. In
      response to 5 days of T(3) treatment, TRbeta1 increased 1.6-fold in liver,
      whereas TRalpha1 remained unchanged. T(3) also induced concomitant increases in
      the protein and mRNA expression of nuclear-encoded subunit COX Vb in liver,
      matched by a 1.3-fold increase in binding to a putative thyroid response element
      (TRE) within the COX Vb promoter in liver, suggesting transcriptional regulation.
      In contrast, T(3) had no effect on COX Vb expression in heart. T(3) produced a
      significant increase in COX III mRNA in liver but decreased COX III mRNA in
      heart. These changes were matched by parallel alterations in mitochondrial
      transcription factor A expression in both tissues. In contrast, COX I protein
      increased in both liver and heart 1.7- and 1.5-fold (P < 0.05), respectively.
      These changes in COX I closely paralleled the T(3)-induced increases in COX
      activity observed in both of these tissues. In liver, T(3) induced a coordinated
      increase in the expression of the nuclear (COX Vb) and mitochondrial (COX I)
      genomes at the protein level. However, in heart, the main effect of T(3) was
      restricted to the expression of mitochondrial DNA subunits. Thus our data suggest
      that T(3) regulates the expression of COX subunits by both transcriptional and
      posttranscriptional mechanisms. The nature of this regulation differs between
      tissues possessing a high mitochondrial content, like liver and heart.

PMID- 14970007
TI  - Hypoglycemia and the sympathoadrenal system: neurogenic symptoms are largely the
      result of sympathetic neural, rather than adrenomedullary, activation.
AB  - The relative contributions of the sympathetic nervous system and the adrenal
      medullae, the two components of the sympathoadrenal system, to the manifestations
      of hypoglycemia are largely unknown. We tested the hypothesis that the neurogenic
      symptoms of hypoglycemia are largely the result of sympathetic neural activation.
      To do so, we quantitated neurogenic symptoms, as well as norepinephrine (NE)
      kinetics and selected hemodynamic changes, during hyperinsulinemic euglycemic and
      stepped hypoglycemic clamps in 15 healthy control subjects (Controls) and four
      bilaterally adrenalectomized patients (ADX). Plasma epinephrine responses to
      hypoglycemia were virtually absent in ADX, as expected. Neurogenic symptom scores
      increased to higher values during the hypoglycemic compared with the euglycemic
      clamps in both Controls (P < 0.0001) (e.g., final scores of 7.8 +/- 1.2 vs. 3.0
      +/- 0.7) and ADX (P < 0.0001) (e.g., final scores of 10.8 +/- 4.1 vs. 2.5 +/-
      1.0). Plasma NE concentrations (P < 0.0001) and systemic NE spillover (P =
      0.0007) increased during the hypoglycemic compared with the euglycemic clamps in
      Controls but not in ADX. Similarly, heart rate increased (P = 0.0104), diastolic
      blood pressure decreased (P = 0.0003), and forearm blood flow increased (P <
      0.0001) during the hypoglycemic compared with the euglycemic clamps in Controls
      but not in ADX. These data indicate that the neurogenic symptoms of hypoglycemia
      are largely the result of sympathetic neural, rather than adrenomedullary,
      activation. They also suggest that the plasma NE and hemodynamic responses to
      hypoglycemia are largely the result of adrenomedullary, rather that sympathetic
      neural, activation.

PMID- 14970008
TI  - Subcutaneous abdominal preadipocyte differentiation in vitro inversely correlates
      with central obesity.
AB  - Expansion of adipose tissue mass results from increased number and size of
      adipocyte cells. We hypothesized that subcutaneous abdominal preadipocytes in
      obese individuals might have an intrinsically higher propensity to differentiate
      into adipocytes. Thus we investigated the relationship between obesity and the
      level of in vitro preadipocyte differentiation in Pima Indians. Subcutaneous
      abdominal stromal vascular fractions containing preadipocytes were cultured from
      58 nondiabetic subjects [31 M/27 F, 30 +/- 6 yr, body fat 34 +/- 8% by dual
      energy X-ray absorptiometry (means +/- SD)]. The average percentage of
      preadipocyte differentiation (PDIFF; cell count by microscopy) was 11 +/- 11%
      (range 0.2-51%). PDIFF correlated negatively with percent body fat (r = -0.35, P
      = 0.006) and waist circumference (r = -0.45, P = 0.0004). Multiple regression
      analysis indicated that waist circumference (P = 0.01), sex (P = 0.01), and
      percent body fat (P = 0.05) were significant determinants of PDIFF. Molecular
      characterization of predifferentiated cultured cells was performed by real-time
      PCR measurements of glucocorticoid receptor-alpha (GRalpha), insulin-like growth
      factor I receptor (IGF-IR), peroxisome proliferator-activated receptor-gamma
      (PPARgamma), enhancer-binding protein GATA-3, CCAAT/enhancer-binding protein
      alpha undifferentiated protein (CUP/AP-2alpha), and endothelial cell-specific
      marker 2 (ECSM2). The mRNA concentrations of GRalpha correlated with PDIFF (r =
      0.29, P = 0.03), but the others did not (IGF-IR, r = 0.003, P = 1.0; PPARgamma, r
      = -0.1, P = 0.5; GATA-3, r = 0.02, P = 0.9; CUP/AP-2alpha, r = -0.2, P = 0.1;
      ECSM2, r = 0.04, P = 0.7). Contrary to our hypothesis, the results may indicate a
      blunted in vitro differentiation potential of preadipocytes in centrally obese
      individuals. The lower differentiation potential of preadipocytes in the obese
      subjects might be due, at least partly, to decreased glucocorticoid receptor
      expression.

PMID- 14970009
TI  - Regulation by glucose and calcium of the carboxylmethylation of the catalytic
      subunit of protein phosphatase 2A in insulin-secreting INS-1 cells.
AB  - Previously, we reported that the catalytic subunit of protein phosphatase 2A
      (PP2Ac) undergoes carboxylmethylation (CML) at its COOH-terminal leucine, and
      that inhibitors of such a posttranslational modification markedly attenuate
      nutrient-induced insulin secretion from isolated beta-cells. More recent studies
      have suggested direct inhibitory effects of glucose metabolites on PP2A activity
      in isolated beta-cells, implying that inhibition of PP2A leads to stimulation of
      insulin secretion. Because the CML of PP2Ac has been shown to facilitate the
      holoenzyme assembly and subsequent functional activation of PP2A, we investigated
      putative regulation by glucose of the CML of PP2Ac in insulin-secreting (INS)-1
      cells. Our data indicated a marked inhibition by specific intermediates of
      glucose metabolism (e.g., citrate and phosphoenolpyruvate) of the CML of PP2Ac in
      INS-1 cell lysates. Such inhibitory effects were also demonstrable in intact
      cells by glucose. Mannoheptulose, an inhibitor of glucose metabolism, completely
      prevented inhibitory effects of glucose on the CML of PP2Ac. Moreover, glucose
      mediated inhibition of the CML of PP2Ac was resistant to diazoxide, suggesting
      that glucose metabolism and the generation of glucose metabolites might control
      inhibition of the CML of PP2Ac. A membrane-depolarizing concentration of KCl also
      induced inhibition of the CML of PP2Ac in intact INS cells. On the basis of these
      data, we propose that glucose metabolism and increase in intracellular calcium
      facilitate inhibition of the CML of PP2Ac, resulting in functional inactivation
      of PP2A. This, in turn, might retain the key signaling proteins of the insulin
      exocytotic cascade in their phosphorylated state, leading to stimulated insulin
      secretion.

PMID- 14970010
TI  - My legs only hurt when I stand up!

PMID- 14970011
TI  - Does filling the crack break more of the back?

PMID- 14970012
TI  - Imaging NeuroAIDS.

PMID- 14970013
TI  - The high-field-strength curmudgeon.

PMID- 14970014
TI  - Axial loading during MR imaging can influence treatment decision for symptomatic
      spinal stenosis.
AB  - BACKGROUND AND PURPOSE: Previous studies have shown that axial loading can narrow
      the spinal canal. However, the clinical significance is unclear. The purpose of
      this study was to determine whether the narrowing of the spinal canal with axial
      loading during MR imaging could influence treatment decision for spinal stenosis.
      METHODS: Two hundred patients with clinical symptoms of spinal stenosis underwent
      routine MR imaging and then immediately underwent axially loaded MR imaging. We
      selected 20 of these patients because they had narrowing of the spinal canal
      shown on the axially loaded images. Three experienced neurosurgeons evaluated
      these 20 patients based on clinical information and routine MR images. The same
      neurosurgeons were then asked for second treatment decisions based on the same
      clinical information but with axially loaded MR images. RESULTS: Axial loading
      during MR imaging of the lumbar spine can influence neurosurgeons in their
      treatment decisions for symptomatic spinal stenosis. For this selected group of
      patients, all three neurosurgeons changed their treatment decision from
      conservative management to decompressive surgery for five patients when shown the
      axially loaded MR images. For two other patients, two neurosurgeons changed their
      treatment decisions, and for three additional patients, one neurosurgeon changed
      his treatment decision, all based on the axially loaded MR images. Treatment was
      not changed from surgical to medical management for any of the patients when
      shown the axially loaded images. CONCLUSION: In selected patients with spinal
      stenosis and apparent narrowing of the spinal canal shown by axially loaded MR
      imaging, the additional information gained from this technique can influence
      experienced neurosurgeons in their treatment decisions.

PMID- 14970015
TI  - Vertebroplasty: cement leakage into the disc increases the risk of new fracture
      of adjacent vertebral body.
AB  - BACKGROUND AND PURPOSE: Patients successfully treated with vertebroplasty often
      return with new pain caused by a new vertebral body fracture. The new fractures
      often are adjacent to the vertebral bodies that were initially treated. In our
      clinical work, we have observed that cement leakage into the disk increases the
      risk of new fracture of the adjacent vertebral body. This study analyzed the risk
      of new fractures of adjacent vertebral bodies in relationship to cement leakage
      into the disk. METHODS: This study was based on 38 patients with painful
      compression fractures treated with vertebroplasty. Patients who returned with new
      pain after initial successful vertebroplasty were evaluated by repeat MR imaging.
      We analyzed the incidence of new fractures of adjacent vertebral bodies in
      relationship to cement leakage into the disk that had occurred during the initial
      vertebroplasty. RESULTS: Fourteen patients developed new fractures during the
      follow-up period. In 10 patients, the new fractures were associated with cement
      leakage into the disk, whereas four patients had new fractures that were not
      associated with cement leakage into the disk. This difference was statistically
      significant (P =.018). A detailed analysis showed that 58% of vertebral bodies
      adjacent to a disk with cement leakage fractured during the follow-up period
      compared with 12% of vertebral bodies adjacent to a disk without cement leakage
      (P <.0005). CONCLUSION: Leakage of cement into the disk during vertebroplasty
      increases the risk of a new fracture of adjacent vertebral bodies.

PMID- 14970016
TI  - The search for neuroprotective strategies in stroke.

PMID- 14970017
TI  - Whole brain diffusion tensor imaging in HIV-associated cognitive impairment.
AB  - BACKGROUND AND PURPOSE: Quantitative MR imaging strategies may have considerable
      potential for in vivo assessment of neuropathologic changes associated with HIV.
      This investigation evaluated the prognostic significance of whole brain histogram
      derived diffusion tensor imaging indices with respect to severity of cognitive
      impairment and measures of clinical status in cases of HIV. METHODS: Quantitative
      indices derived with diffusion tensor imaging, including whole brain fractional
      anisotropy and the apparent diffusion coefficient, were compared for six patients
      with HIV and eight control volunteers. Relationships between whole brain indices
      and specific measures of dementia severity and clinical status were examined.
      RESULTS: Whole brain fractional anisotropy was reduced in patients with HIV and
      was significantly associated with severity of dementia, as indicated by several
      widely used clinical and functional status measures. Summary fractional
      anisotropy measures were more prognostic of dementia status than were apparent
      diffusion coefficient measures. CONCLUSION: Findings from this investigation
      support the use of diffusion tensor imaging for noninvasive MR imaging
      measurement of neuropathologic changes in studies of HIV-associated cognitive
      impairment.

PMID- 14970018
TI  - Diffusion-weighted imaging in the follow-up of treated high-grade gliomas: tumor
      recurrence versus radiation injury.
AB  - BACKGROUND AND PURPOSE: Diffusion-weighted (DW) MR imaging is a means to
      characterize and differentiate morphologic features, including edema, necrosis,
      and tumor tissue, by measuring differences in apparent diffusion coefficient
      (ADC). We hypothesized that DW imaging has the potential to differentiate
      recurrent or progressive tumor growth from treatment-induced damage to brain
      parenchyma in high-grade gliomas after radiation therapy. METHODS: We
      retrospectively reviewed follow-up conventional and DW MR images obtained
      starting 1 month after completion of radiation treatment with or without
      chemotherapy for histologically proved high-grade gliomas. Eighteen patients with
      areas of abnormal enhancing tissue were identified. ADC maps were calculated from
      echo-planar DW images, and mean ADC values and ADC ratios (ADC of enhancing
      lesion to ADC of contralateral white matter) were compared with final diagnosis.
      Recurrence was established by histologic examination or by clinical course and a
      combination of imaging studies. RESULTS: Recurrence and nonrecurrence could be
      differentiated by using mean ADC values and ADC ratios. ADC ratios in the
      recurrence group showed significantly lower values (mean +/- SD, 1.43 +/- 0.11)
      than those of the nonrecurrence group (1.82 +/- 0.07, P <.001). Mean ADCs of the
      recurrent tumors (mean +/- SD, 1.18 +/- 0.13 x 10(-3) mm/s(2)) were significantly
      lower than those of the nonrecurrence group (1.40 +/- 0.17 x 10(-3) mm/s(2), P
      <.006). CONCLUSION: Assessment of ADC ratios of enhancing regions in the follow
      up of treated high-grade gliomas is useful in differentiating radiation effects
      from tumor recurrence or progression.

PMID- 14970019
TI  - Early diagnosis of central pontine myelinolysis with diffusion-weighted imaging.
AB  - Central pontine myelinolysis (CPM) occurs in the setting of rapidly corrected
      hyponatremia, especially in chronically debilitated patients. Conventional CT and
      MR imaging findings lag the clinical manifestations of CPM. We present a case in
      which restricted diffusion was identified within the central pons by using MR
      diffusion-weighted imaging within 24 hours of onset of patient tetraplegia and
      before findings were conspicuous with conventional MR imaging sequences (T1, T2,
      and fluid-attenuated inversion recovery).

PMID- 14970020
TI  - Glial tumor grading and outcome prediction using dynamic spin-echo MR
      susceptibility mapping compared with conventional contrast-enhanced MR:
      confounding effect of elevated rCBV of oligodendrogliomas [corrected].
AB  - BACKGROUND AND PURPOSE: The MR imaging characteristics of oligodendrogliomas and
      astrocytomas on spin-echo (SE), echo-planar relative cerebral blood volume (rCBV)
      maps, to our knowledge, have not previously been emphasized. We compared the
      specificity of SE rCBV mapping with that of conventional, contrast material
      enhanced MR imaging in differentiating high- from low-grade glial tumors and in
      predicting survival of patients with these lesions. METHODS: Thirty consecutive
      adult patients with suspected gliomas underwent conventional and rCBV MR imaging.
      Representative maximal rCBV regions of interest were chosen from each lesion.
      Resultant values were normalized to those of corresponding, contralateral,
      uninvolved regions. These normalized CBV (nCBV) values were correlated with
      degree of contrast enhancement, histopathologic tumor grade, and survival.
      RESULTS: Twenty-two patients had astroctyomas and eight had oligodendrogliomas.
      With an nCBV cutoff ratio of 1.5, 13 of 13 high-grade astrocytomas were correctly
      categorized, three of which did not enhance. Seven of nine low-grade astrocytomas
      were correctly classified by their nCBV values, including one enhancing lesion.
      Of eight oligodendrogliomas, four of four high-grade and two of four low-grade
      tumors had elevated nCBV values; two low-grade oligodendrogliomas enhanced, one
      with nCBV greater than 1.5 and one with nCBV less than 1.5. In 19 patients with
      astrocytoma for whom survival data were available, correlation with survival was
      better for nCBV (mean survival 91 +/- 14 months for nCBV < 1.5 versus 24 +/- 27
      months for nCBV > 1.5, P <.0001) than for enhancement (mean survival 61 +/- 35
      months without enhancement versus 22 +/- 29 months with enhancement, P =.03).
      CONCLUSION: Elevated SE rCBV was a sensitive, but not specific, marker for high
      grade histopathology: all high-grade tumors had nCBV foci values greater than
      1.5. No tumor with nCBV region of interest less than 1.5 was high grade (100%
      predictive value for excluding high grade). Degree of nCBV elevation was a
      stronger predictor of both tumor grade and survival than was degree of
      enhancement. A significant proportion of low-grade glial neoplasms, most notably
      oligodendrogliomas, may display high rCBV foci not reflective of high-grade
      histopathology.

PMID- 14970021
TI  - The insula: anatomic study and MR imaging display at 1.5 T.
AB  - BACKGROUND AND PURPOSE: The insula is important for gustatory sensation, motor
      speech control, vestibular function, and sympathetic control of cardiovascular
      tone. The purpose of this study was to test two hypotheses: 1) gross anatomic
      study of the insula will disclose reproducible patterns of insular structure, and
      2) analysis of MR appearance will enable physicians to recognize these patterns
      on imaging studies. METHODS: Gross insular anatomy was determined in 16 normal
      human cadaveric hemispheres. The 1.5-T MR images of 300 insulae were analyzed to
      determine the gyral and sulcal patterns displayed; their relationship to the
      Heschl gyrus, to the overlying opercula, and to the vertical planes perpendicular
      to the Talairach-Tournoux baseline at the anterior commissure (VAC) and posterior
      commissure (VPC); their continuity into the orbitofrontal cortex; and appropriate
      landmarks for the anterior border, apex, and posterior border of the insula.
      RESULTS: MR images displayed the central sulcus of the insula (97%); the anterior
      (99%), middle (78%), and posterior (98%) short insular gyri that converge to the
      apex (100%) anteriorly; and the anterior (99%) and posterior (58%) long insular
      gyri posteriorly. The middle short gyrus was often hypoplastic (33%). The
      anterior intersections of the internal and external capsules typically delimit
      the anterior insular border (87%). VAC intersects the anterior insula (99%),
      usually at the precentral sulcus. The Heschl gyrus circumscribes the
      posteroinferior insula (100%). VPC demarcates the posterior insular border (94%).
      CONCLUSION: The two hypotheses were proved correct. The insula shows reproducible
      patterns of gross anatomy that are demonstrable on routine clinical MR images
      obtained at 1.5 T.

PMID- 14970022
TI  - CT brain prescriptions in Talairach space: a new clinical standard.
AB  - BACKGROUND AND PURPOSE: Head CT prescriptions are currently plagued by intra- and
      intersubject image variance and do not match standardized MR imaging planes. We
      developed and tested a simple method to improve CT precision and approximate the
      Talairach reference standard advocated for MR imaging. METHODS: We
      retrospectively reviewed midline sagittal T2-weighted brain MR images of 126
      consecutive patients to determine the mean angle subtended by the Talairach
      anterior commissure-posterior commissure (AC-PC) line and the hard palate. On the
      basis of this data set, a new head CT protocol was instituted with pitch
      similarly prescribed relative to the hard palate as identified on the lateral CT
      scout film. We then compared the precision of the new protocol, our former method
      (nominally parallel to the orbito-meatal line) and fixed-gantry angulation. Two
      head CT studies from 50 consecutive patients imaged with our old protocol and 50
      consecutive patients imaged with our new protocol were reviewed for a total of
      200 CT examinations. RESULTS: The Talairach AC-PC line was rotated 12.0 degrees
      +/- 6.1 degrees from the hard palate line and 15.6 degrees +/- 10.1 degrees from
      the axial plane of the magnet. The new CT protocol approximated the Talairach
      referenced MR images obtained at our institution and improved intrapatient CT
      scan precision compared with fixed-gantry selection (P <.004) and compared with
      our previous prescription technique (P <.064; P <.025, controlling for excessive
      head extension). CONCLUSION: By prescribing CT images angled +12 degrees from the
      hard palate, a structure readily identified by technologists, interscan precision
      can be improved and Talairach-referenced MR imaging studies can be approximated.
      Along with AC-PC-referenced MR imaging studies, we advocate this CT protocol as a
      new clinical standard.

PMID- 14970023
TI  - Relationships between angiographic findings and National Institutes of Health
      stroke scale score in cases of hyperacute carotid ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Stroke severity in cases of hyperacute carotid ischemic
      stroke may be related to site of arterial occlusion. We evaluated the
      relationships between National Institutes of Health Stroke Scale (NIHSS) scores
      and findings on intra-arterial digital subtraction angiograms (IA-DSA) of
      patients with ischemic stroke within 6 hr of stroke onset. METHODS: A total of 43
      consecutive patients (38 men and five women; mean age, 69.4 +/- 8.7 years) with
      ischemic stroke in the carotid territory underwent IA-DSA within 6 hr of stroke
      onset. Baseline NIHSS score was assessed immediately before IA-DSA. Patients were
      divided into four groups according to site of arterial occlusion: 1) the internal
      carotid artery (ICA group, n = 10); 2) stem of the middle cerebral artery or stem
      of the anterior cerebral artery (Stem group, n = 14); 3) branches of middle
      cerebral artery or anterior cerebral artery (Branch group, n = 11); and 4) no
      arterial occlusion (Normal group, n = 8). RESULTS: Mean (+/-SD) NIHSS score was
      14.7 +/- 7.4. The interval from stroke onset to IA-DSA study was 205 +/- 76 min.
      NIHSS score was higher in the ICA group (median, 23; range, 6-32) than in the
      Branch (median, 17; range, 11-25; P =.02) or Normal (median, 15; range, 2-17; P
      <.001) groups but was not higher than in the Stem group (median, 6; range, 1-11;
      P =.73). Sensitivity-specificity curve analysis suggested an NIHSS score > or =
      10 as indicative of arterial occlusion of the carotid system. A total of 96.9% of
      patients with NIHSS scores > or = 10 displayed arterial occlusion, and 63.6% of
      patients with NIHSS scores <10 displayed no arterial occlusion. CONCLUSION: NIHSS
      score is related to site of arterial occlusion in cases of hyperacute carotid
      ischemic stroke. An NIHSS score of 10 seems to represent the cut-off for
      discriminating between patients with arterial occlusion and patients without.

PMID- 14970024
TI  - Correlation of angiographic circulation time and cerebrovascular reserve by
      acetazolamide-challenged single photon emission CT.
AB  - BACKGROUND AND PURPOSE: Although cerebral circulation time (CCT) is one of the
      main parameters in cerebral blood flow measurements, its clinical significance is
      controversial. To assess the importance of CCT by using a nondiffusible
      indicator, we studied the relationship between angiographic CCT and
      cerebrovascular reserve. METHODS: Twenty-eight patients, each with a unilateral
      occlusive lesion in the internal carotid artery or middle cerebral artery, were
      examined. To assess the CCT, the regional arteriocapillary circulation time
      (rACCT) was measured by angiography and the ratio of the value on the occlusive
      side to the value on the contralateral side was calculated as the rACCT ratio. To
      estimate the cerebrovascular reserve, acetazolamide-challenged single photon
      emission CT was used. Patients with a decreased cerebrovascular reserve were
      defined as the "poor reserve" group, and those without a decrease were defined as
      the "normal reserve" group. The ratio of the radioactivity count on the occlusive
      side to the count on the contralateral side was calculated as the asymmetry
      index, and the proportion of the acetazolamide-challenged asymmetry index to the
      baseline asymmetry index was defined as the regional reactivity index. RESULTS:
      The rACCT ratio in the poor reserve group (n = 19) was significantly (P <.001)
      larger than that in the normal reserve group (n = 9), and a significant
      correlation (r = -0.83, P <.01) was found between the rACCT ratio and the
      regional reactivity index. CONCLUSION: The angiographic CCT and the cerebral
      vasoreactivity to acetazolamide on single photon emission CT were well
      correlated, suggesting that measurement of the CCT by using a nondiffusible
      indicator could be used as an index of cerebrovascular reserve.

PMID- 14970025
TI  - Distinguishing between anterior cerebral artery and middle cerebral artery
      perfusion by color-coded perfusion direction mapping with arterial spin labeling.
AB  - The purpose of this study was to evaluate collateral circulation by describing
      anterior cerebral artery and middle cerebral artery perfusion areas. Pairs of
      image sets spin labeled on the medial and lateral side were used. A pixel-by
      pixel t test was performed, with blue gradation used to display lateral perfusion
      (ie, middle cerebral artery) and orange gradation for anterior cerebral artery
      perfusion. Extensions of anterior cerebral artery perfusion areas in cases of
      middle cerebral artery stenosis were described. This method may aid in estimation
      of collateral circulation for stroke treatment.

PMID- 14970026
TI  - MR findings of cortical blindness following cerebral angiography: is this entity
      related to posterior reversible leukoencephalopathy?
AB  - We describe MR findings in three patients who experienced transient cortical
      blindness following cerebral angiograms. All angiograms were performed by using
      the same nonionic contrast medium. On the basis of similar clinical and
      radiologic findings, we believe that this entity is closely related to and
      probably has the same pathophysiology as posterior reversible
      leukoencephalopathy.

PMID- 14970027
TI  - CT findings and clinical features as markers for patient outcome in primary
      pontine hemorrhage.
AB  - BACKGROUND AND PURPOSE: The overall mortality rate of primary pontine hemorrhage
      (PPH) in recent studies is 40-50%. The aim of the present study was to analyze
      the predictive value of clinical and neuroradiologic parameters concerning the
      outcome of patients with PPH. METHODS: We reviewed the clinical data of 29
      consecutive patients (mean age, 59 +/- 13.5 years; 12 women, 17 men) with PPH.
      National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS)
      scores were assessed on admission, and NIHSS, GCS, and Glasgow Outcome Scale
      (GOS) scores were assessed on discharge. The hemorrhage volume was calculated by
      using a previously published formula. Clinical manifestations, outcome, and
      volume and location of the bleeding were correlated. RESULTS: The mean GCS score
      on admission was 6.8 +/- 3.9 and increased to 9.0 +/- 3.9 on discharge. The NIHSS
      score improved from 29.1 +/- 12.5 to 12.1 +/- 7.3. Nine patients (31%) died as a
      result of PPH after 5 +/- 3 days. The mean GOS score was 3.0 +/- 1.5 (3.9 +/- 0.8
      for patients who survived). Arterial hypertension was the most common risk factor
      (90%); other causes were anticoagulation therapy (7%) and amyloid angiopathy
      (3%). A high correlation was observed between a poor outcome (GOS score < 4) and
      hematoma volume greater than 4 mL (P =.006), ventral hemorrhage (P <.001), and
      necessity for mechanical ventilation (P <.001). Patients with dorsally located
      hematomas less than 4 mL in volume had a significantly better outcome.
      CONCLUSION: The prognosis of PPH is better than commonly expected. Most patients
      with moderate neurologic deficits on admission and dorsally located small
      hematomas are able to survive PPH with minor neurologic deficits.

PMID- 14970028
TI  - Pretransplantation conditioning influence on the occurrence of cyclosporine or FK
      506 neurotoxicity in allogeneic bone marrow transplantation.
AB  - BACKGROUND AND PURPOSE: Transplantation conditioning regimens have been shown to
      affect the brain imaging appearance in patients with cyclosporine or FK-506
      neurotoxicity. We assessed whether the occurrence of neurotoxicity was affected
      by the choice of conditioning regimen used before allogeneic bone marrow
      transplantation (allo-BMT). METHODS: An allo-BMT was performed in 290 patients
      conditioned before transplantation with myeloablative therapy. Neurotoxicity from
      cyclosporine or FK-506 developed in 21 (7.2%) of these patients, as confirmed
      with CT or MR imaging. Two hundred seventy-four (94%) of these 290 patients were
      conditioned with minor variations of one of five fundamental regimens:
      cyclophosphamide (Cy)/busulfan (n = 97), Cy/total body irradiation (TBI) (n =
      122), Cy/thiotepa/TBI (n = 40),
      bischloroethylnitrosourea/etoposide/cytarabine/melphalan, or BEAM (n = 10), and
      Cy/thiotepa/busulfan (n = 5). The remaining 16 patients were prepared with
      variable regimens. The rates of occurrence of cyclosporine or FK-506
      neurotoxicity relative to these conditioning regimens were compared. RESULTS: The
      lowest rate of cyclosporine or FK-506 neurotoxicity was found in those patients
      conditioned with Cy (2 days)/busulfan (4 days) (5.1%) or Cy (2 days)/TBI (4 days)
      (5.9%). Rate of neurotoxicity increased with lengthier conditioning regimens. A
      high rate of neurotoxicity was present in those patients conditioned with Cy (4
      days)/TBI (4 days) (13.7%), and this was statistically significant (P <.05) when
      compared with Cy (2 days)/busulfan (4 days). CONCLUSION: The rate of occurrence
      of cyclosporine or FK-506 neurotoxicity varies with the conditioning regimen
      used, with lengthier regimens associated with a higher rate of neurotoxicity. As
      the length of the conditioning regimen equates to the total dose of chemotherapy
      administered, it suggests that the intensity of the regimen is correlated to the
      predisposition to neurotoxicity from cyclosporine or FK-506.

PMID- 14970029
TI  - MR imaging in toxoplasmosis encephalitis after bone marrow transplantation:
      paucity of enhancement despite fulminant disease.
AB  - We present a patient who underwent bone marrow transplantation (BMT) after
      developing chronic myelocytic leukemia. Four months after BMT, he became comatose
      and died. MR imaging revealed multifocal brain lesions that were progressive but
      produced no edema. Postcontrast studies revealed that most of the lesions were
      nonenhancing. There was only discrete, irregular leptomeningeal enhancement with
      possible minimal enhancement of the cortex and subcortical white matter. Autopsy
      showed overwhelming toxoplasmosis encephalitis. This case illustrates that
      toxoplasmosis lesions may lack obvious contrast enhancement in the brain of the
      immunocompromised patients, despite severe involvement. Recognition of this
      unusual MR imaging manifestation of toxoplasmosis should lead to earlier
      diagnosis and treatment.

PMID- 14970030
TI  - Paramagnetic effect of supplemental oxygen on CSF hyperintensity on fluid
      attenuated inversion recovery MR images.
AB  - BACKGROUND AND PURPOSE: Oxygen has a known paramagnetic effect and increases CSF
      signal intensity on fluid-attenuated inversion recovery (FLAIR) MR images. The
      purposes of this study were to investigate the effect of supplemental oxygen on
      CSF signal intensity and the arterial partial pressure of oxygen and to determine
      the possible synergistic effect of oxygen and albumin on T1 shortening effect in
      vitro. METHODS: Six healthy volunteers underwent FLAIR MR imaging of the brain
      before and during inhalation of 10 to 15 L/min of 100% oxygen for < or = 30 min.
      The signal intensity was measured in the subarachnoid spaces and various tissues
      and correlated with estimated arterial partial pressure of oxygen and arterial
      carbon dioxide pressure. In vitro measurements were also obtained by using two
      sets of saline-filled tubes with various concentrations of albumin, one of which
      was exposed to increased oxygen levels. In vitro T1 relaxation times were
      calculated to assess the possible synergistic effect of oxygen and albumin.
      RESULTS: FLAIR images of healthy volunteers showed increased CSF signal intensity
      within the basal cisterns and sulci along the cerebral convexities. The CSF
      hyperintensity was observed immediately after the initiation of supplemental
      oxygen and remained stable during the oxygen administration. There was
      approximately a 4- to 5.3-fold increase in signal intensity with supplemental
      oxygen. The phantom experiments showed a T1 shortening effect of oxygen. Albumin
      significantly altered T1 relaxation time only at high concentrations of albumin.
      CONCLUSION: Inhalation of increased levels of oxygen led to readily detectable
      CSF hyperintensity on FLAIR images of healthy volunteers. No significant
      synergetic effect of albumin and oxygen was noted.

PMID- 14970031
TI  - Extracerebral cavernous hemangioma of the cavernous sinus: diagnosis with MR
      imaging and labeled red cell blood pool scintigraphy.
AB  - We present the case of a 64-year-old man with a presumed diagnosis of
      extracerebral cavernous hemangioma involving the cavernous sinus. The diagnosis
      was made on the basis of labeled red cell blood pool scintigraphy findings in
      conjunction with those of MR imaging. This lesion was not altered in appearance
      at 6-year follow-up MR imaging. We also present the labeled red cell blood pool
      scintigraphy findings obtained in three other patients with similar-appearing
      cavernous sinus lesions at MR imaging who underwent subsequent biopsy; histologic
      findings confirmed chondrosarcoma, chordoma, and meningioma, respectively.

PMID- 14970032
TI  - A rare expression of neural crest disorders: an intrasphenoidal development of
      the anterior pituitary gland.
AB  - Congenital abnormalities of the pituitary gland are rare and may be associated
      with midline cranial, orbital, and facial anomalies and with hormonal
      insufficiency. Here we report a case of asymptomatic, abnormal migration of the
      adenohypophysis. The normally developed adenohypophysis was located in the
      sphenoid bone and developed on the intersphenoidal septum, extending from the
      superior pharyngeal wall to the floor of the sella turcica (craniopharyngeal
      canal). The abnormal migration of the pituitary gland was isolated without
      hormonal deficit, brain, or facial developmental anomalies.

PMID- 14970033
TI  - Infarction of the choroid plexus.
AB  - Infarction of the choroid plexus may result from ischemia in the distribution of
      the medial posterior choroidal artery. Diffusion-weighted imaging may depict this
      unusual stroke syndrome. The clinical and radiologic aspects of this rare
      condition are discussed taking into consideration the anatomy and pathophysiology
      of the choroid plexus.

PMID- 14970034
TI  - MR imaging features of a scalp plexiform schwannoma.
AB  - Radiologic findings of a case with scalp plexiform schwannoma-an unusual variant
      of the benign, solitary schwannoma in the skin-are reported. T2-weighted MR
      imaging exhibited the most specific features: a multinodular pattern and
      hypointense capsule that separated the tumor from surrounding soft tissue. A
      surgical specimen was histologically confirmed as schwannoma. The MR imaging
      findings reported herein may aid in the preoperative diagnosis of this relatively
      rare scalp tumor.

PMID- 14970035
TI  - Noninvasive MR cisternography with fluid-attenuated inversion recovery and 100%
      supplemental O(2) in the evaluation of neurocysticercosis.
AB  - SUMMARY: We describe an MR protocol for the noninvasive imaging of the
      subarachnoid space, which we use in patients with suspected neurocysticercosis in
      this space. It consists of a fluid-attenuated inversion recovery sequence
      performed 5 minutes after the continuous inhalation of 100% O(2) with a resultant
      increase in the signal intensity of the CSF that leads to a greater conspicuity
      of cyst walls in relation to the cortex and the extraventricular CSF.

PMID- 14970036
TI  - Endovascular treatment of intracranial wide-necked aneurysms using three
      dimensional coils: predictors of immediate anatomic and clinical results.
AB  - BACKGROUND AND PURPOSE: Aneurysms with a wide neck constitute a persistent
      challenge for endovascular therapy with coils. Our purpose was to evaluate the
      immediate anatomic and clinical results of treating intracranial wide-necked
      aneurysms by using three-dimensional (3D) coils. METHODS: During a 2-year period,
      160 aneurysms (116 with a neck < or = 4 mm, group A; 44 with a neck > 4 mm, group
      B) in 157 patients in eight participating centers were consecutively treated. The
      procedure consisted first of framing the aneurysm with one or more 3D spherical
      coils and then filling it with helical coils. Results were evaluated with
      univariate analysis. Multivariate analysis was used to identify independent
      predictors of these results. RESULTS: Angiographic occlusion was complete in 84
      (72%) and 30 (68%) aneurysms in groups A and B, respectively. Mean percentage of
      volumic occlusion in these groups was 30.9% and 29.2%, respectively.
      Perioperative morbidity and mortality rates were 4%, respectively, in group A and
      2%, respectively, in group B. No significant difference between the two groups
      was observed. However, percentage of volumic occlusion correlated with sac-to
      neck ratio less than 1.5 (P =.061) and with sac size (P =.002) except when three
      or more 3D coils per aneurysm were used (P =.222). The better the percentage of
      volumic occlusion, the better the degree of angiographic occlusion (P =.004).
      Percentage of volumic occlusion was an independent predictor of angiographic
      complete occlusion (P =.001). World Federation of Neurological Surgeons
      subarachnoid hemorrhage scale grade 5 was an independent predictor of
      perioperative mortality (P =.043). CONCLUSION: Three-dimensional coils proved to
      be useful for improving coil packing and angiographic and volumic occlusion of
      aneurysms with a neck greater than 4 mm, at the time of treatment, provided the
      sac-to-neck ratio was 1.5 or greater, and the largest number of 3D coils were
      first positioned.

PMID- 14970037
TI  - Intracranial aneurysms treated with Guglielmi detachable coils: midterm clinical
      and radiological outcome in 97 consecutive Chinese patients in Hong Kong.
AB  - BACKGROUND AND PURPOSE: Use of Guglielmi detachable coils (GDCs) has proved to be
      a promising endovascular treatment for intracranial aneurysms. This study aimed
      to evaluate midterm clinical and radiologic outcomes of this treatment in Hong
      Kong Chinese patients, 68% of whom had small aneurysms (< or =5 mm). METHODS: We
      included 97 consecutive patients in whom GDCs were placed with curative intent.
      The patients presented with subarachnoid hemorrhage (n = 80) or mass effect (n =
      17). The aneurysms measured 5 cm +/- 2.8 mm; 68% were < or =5 mm. All patients
      were followed up clinically for an average of 54.5 +/- 20.9 months and
      radiologically with sequential digital subtraction angiography at 6 and 18
      months. RESULTS: Total occlusion of the aneurysm was successfully achieved in
      71.1% of patients after the initial treatment and in 82.5% after subsequent
      treatments. The retreatment rate was 17.5%. Procedure-related complication and
      mortality rates were 11.3% and 0%, respectively. The overall mortality was 5%,
      including mortality due to treatment failure in 1%. Neurologic outcomes were
      excellent in 77% of patients. Improved neurologic status, unchanged status, and
      deteriorated status was noted in 61.5%, 22%, and 16.5% of patients, respectively,
      at the end of the follow-up period. Intrinsic differences existed between Chinese
      and Western patients regarding the size of the aneurysm at presentation,
      periprocedural complications, and progression patterns of anatomic outcomes.
      CONCLUSION: Endovascular coiling with GDCs is a reasonably effective and safe
      treatment for intracranial aneurysms in this group of Hong Kong Chinese patients,
      with favorable clinical and radiologic outcomes.

PMID- 14970038
TI  - Endovascular treatment of anterior choroidal artery aneurysms.
AB  - BACKGROUND AND PURPOSE: Ischemic stroke is the most common complication after
      surgical clipping of anterior choroidal artery (AChA) aneurysms, and the reported
      morbidity-mortality rates vary from 5% to 50%. We report the findings in a series
      of 18 consecutive patients who underwent endovascular treatment (EVT) for an AChA
      berry aneurysm. METHODS: In this retrospective study, the aneurysms were defined
      according to their size and position, the presence of a concomitant arteriovenous
      malformation (AVM), the mode of presentation. The patients were clinically
      assessed before and after the EVT, as well as at each angiographic follow-up.
      RESULTS: All were small-sized aneurysms, with greater diameters ranging from 2 to
      8 mm (mean, 4 mm), arising from the supraclinoid internal carotid artery close to
      the origin of the AChA. Two were AVM-associated aneurysms. Fourteen patients
      (14/18 [78%]) presented with subarachnoid hemorrhage. All aneurysms were
      selectively embolized with coils. There was one (1/18 [5.5%]) treatment-related
      death due to aneurysm perforation. Another patient (1/18 [5.5%]) developed a
      transient controlateral hemiparesis. Fourteen patients (14/18 [78%]) were
      followed up clinically and angiographically for 3-32 months (mean, 14 months).
      None of them (re)hemorrhaged during this period. CONCLUSION: The EVT of AChA
      berry aneurysms is effective to protect from rebleeding. Our complication rate
      compares favorably with those of the surgical series.

PMID- 14970039
TI  - A novel two-stage technique for construction of experimental aneurysms.
AB  - A two-staged technique for construction of experimental aneurysms in swine is
      described. The jugular vein is initially anastomosed to the carotid artery.
      Spontaneous hypertrophy of the vein is modeled by placing restraining sutures to
      create a fusiform aneurysm. Subsequent endovascular closure of this aneurysm
      leaves a sidewall aneurysm pouch. Staging allows maturation of the anastomosis,
      and the technique provides additional targets for endovascular training. Trial
      has been successful in three animals.

PMID- 14970040
TI  - Reocclusion of recanalized arteries during intra-arterial thrombolysis for acute
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Early reocclusion of recanalized arteries has been
      observed after thrombolysis for acute coronary occlusion and has been attributed
      to platelet activation after exposure to thrombolytic agents. We conducted a
      retrospective study to determine the rate of reocclusion during intra-arterial
      thrombolysis for acute ischemic stroke and the effect of reocclusion on
      functional outcome. METHODS: Patients treated for acute ischemic stroke at our
      center between September 2000 and May 2002 received a maximum total dose of 4 U
      of reteplase intra-arterially in 1-U increments via superselective
      catheterization. Pharmacologic thrombolysis was supplemented by mechanical
      thrombolysis with balloon angioplasty or snare manipulation at the occlusion
      site. Angiography was performed after each unit of reteplase or mechanical
      maneuver, and the images were interpreted by a blinded reviewer. Reocclusion was
      defined as partial or complete initial recanalization with occlusion recurring at
      the same site as documented by angiography during the endovascular treatment.
      Reocclusions were treated by further pharmacologic and/or mechanical thrombolysis
      according to the discretion of the treating physician. Clinical evaluations were
      performed before and 24 hr, 7 to 10 days, and 1 to 3 months after treatment.
      RESULTS: Forty-six consecutive patients underwent intra-arterial thrombolysis.
      Reocclusion was observed in eight (17%). Among these patients, initial sites of
      occlusion were in the following arteries: intracranial internal carotid artery (n
      = 2), M1 segment of the middle cerebral artery (n = 3), M1 and M2 segments of the
      middle cerebral artery (n = 2), and basilar artery (n = 1). The mean initial
      National Institutes of Health Scale score for these eight patients was 23.3 +/-
      6.2; mean time from symptom onset to treatment was 4.4 +/- 1.2 hr. The
      reocclusions were treated by using additional doses of reteplase alone (n = 1),
      reteplase with snare maneuver and/or angioplasty (n = 5), reteplase with
      angioplasty or snare and then stent placement (n = 1), and angioplasty with stent
      placement (n = 1). The reocclusions resolved in six of eight patients after
      further treatment. Six patients died and two survived but were severely disabled
      at 1 month (modified Rankin Scale scores of 4 and 5, respectively). Independent
      functional outcome scores (modified Rankin Scale scores of 0-2) were
      significantly lower among patients with angiographically shown reocclusion than
      in those without (0 of 8 versus 17 of 38, P =.02). CONCLUSION: Reocclusion occurs
      relatively frequently during intra-arterial thrombolysis for ischemic stroke and
      seems to be associated with poor clinical outcomes.

PMID- 14970041
TI  - Site-specific thromboembolism: a novel animal model for stroke.
AB  - BACKGROUND AND PURPOSE: To develop a technique for site-specific placement of a
      thrombus of predetermined volume in an animal model for the purpose of evaluating
      methods of intravascular thrombolysis and clot retrieval. METHODS: Six swine were
      subjected to thrombus injection bilaterally in the ascending pharyngeal artery
      (APA). Each animal underwent transfemoral angiography while under general
      anesthesia. A nondetachable balloon catheter and a 3-French microcatheter were
      then advanced into the common carotid artery through a 7-French guide catheter.
      With the microcatheter in the proximal APA and the balloon inflated proximally, a
      bolus of preformed thrombus composed of 0.9 mL of autologous blood and 0.1 mL of
      bovine thrombin (200 IU/mL) was injected through the microcatheter while local
      flow arrest was maintained for 15 min. The balloon was deflated and removed. The
      occluded arteries were observed by serial angiography for 3 hr and then resected
      for gross examination and hematoxylin and eosin staining. RESULTS: Each APA was
      occluded angiographically and did not recanalize during the 3-hr observation
      period. Persistent, proximal progression of thrombus to the superior thyroid
      artery origin occurred in three animals. Gross inspection revealed that the
      resected arteries contained thrombus in the proximal APA but not in the common
      carotid artery. Histologic examination revealed organized thrombus, without
      evidence of intimal injury. CONCLUSION: Our model provides a simple, reliable
      method for site-specific injection of a thrombus of predetermined volume. Site
      specific placement is important for evaluation of the efficacy of thrombolytic
      agents and techniques. Angiographic evidence of brain revascularization can be
      used to grade revascularization and clot volume. The ability to specifically
      localize and estimate clot volume makes our model well suited for the evaluation
      and comparison of thrombolytic agents and endovascular techniques.

PMID- 14970042
TI  - Stent-coil treatment of a distal internal carotid artery dissecting
      pseudoaneurysm on a redundant loop by use of a flexible, dedicated nitinol
      intracranial stent.
AB  - Treatment of dissecting pseudoaneurysms of the distal cervical internal carotid
      artery with preservation of the parent artery by using stents or coils has become
      routine. Tortuosity remains a significant obstacle to successful endovascular
      treatment in some cases. We report the use of a stent-coil technique to treat a
      nonhealing dissecting pseudoaneurysm and associated stenosis with anatomic
      preservation of a redundant loop involving the stented arterial segment. This was
      accomplished by using a Neuroform dedicated intracranial stent.

PMID- 14970043
TI  - External jugular vein vascular malformation: sonographic and MR imaging
      appearances.
AB  - Vascular malformations arising from the wall of the external jugular vein are
      rare. This case series discusses the sonographic and MR imaging appearances of
      four such cases and reviews the literature. The diagnosis should be suggested
      preoperatively particularly because of the close relationship such malformations
      to the external jugular vein, as this helps surgeons to plan the operative
      procedure. The imaging appearances are similar to those of other vascular
      malformations elsewhere in the head and neck.

PMID- 14970044
TI  - Early prenatal MR imaging diagnosis of polymicrogyria.
AB  - The case of a 24-week-old fetus that showed features suggestive of focal cortical
      developmental anomaly at prenatal MR imaging is presented. The anomaly was
      confirmed to be polymicrogyria by 34-week prenatal and the 3-day postnatal MR
      imaging studies. The report demonstrates that the development of polymicrogyria
      can be assessed throughout different stages by prenatal MR imaging. In the case
      reported, the additional presence of periventricular heterotopia strongly
      suggests that a neuronal migration alteration coexisted with a postmigrational
      disorder.

PMID- 14970045
TI  - Imaging appearance of nontuberculous mycobacterial infection of the neck.

PMID- 14970046
TI  - Diabetes group warns vascular complication is underdiagnosed and undertreated.

PMID- 14970047
TI  - New anti-BSE rules imposed.

PMID- 14970048
TI  - Experts urge early investment in bone health.

PMID- 14970057
TI  - Eight days vs 15 days of antibiotics for ventilator-associated pneumonia.

PMID- 14970058
TI  - Expanded screening of newborns for genetic disorders.

PMID- 14970059
TI  - Optimal recall rates following mammography.

PMID- 14970060
TI  - Plasma concentrations of asymmetric dimethylarginine (ADMA) in Colombian women
      with pre-eclampsia.

PMID- 14970061
TI  - Antibiotic use in relation to the risk of breast cancer.
AB  - CONTEXT: Use of antibiotics may be associated with risk of breast cancer through
      effects on immune function, inflammation, and metabolism of estrogen and
      phytochemicals; however, clinical data on the association between antibiotic use
      and risk of breast cancer are sparse. OBJECTIVE: To examine the association
      between use of antibiotics and risk of breast cancer. DESIGN, SETTING, AND
      PARTICIPANTS: Case-control study among 2266 women older than 19 years with
      primary, invasive breast cancer (cases) enrolled in a large, nonprofit health
      plan for at least 1 year between January 1, 1993, and June 30, 2001, and 7953
      randomly selected female health plan members (controls), frequency-matched to
      cases on age and length of enrollment. Cases were ascertained from the
      Surveillance, Epidemiology, and End Results cancer registry. Antibiotic use was
      ascertained from computerized pharmacy records. MAIN OUTCOME MEASURE: Association
      between extent of antibiotic use and risk of breast cancer. RESULTS: Increasing
      cumulative days of antibiotic use were associated with increased risk of incident
      breast cancer, adjusted for age and length of enrollment. For categories of
      increasing use (0, 1-50, 51-100, 101-500, 501-1000, and > or =1001 days), odds
      ratios (95% confidence intervals) for breast cancer were 1.00 (reference), 1.45
      (1.24-1.69), 1.53 (1.28-1.83), 1.68 (1.42-2.00), 2.14 (1.60-2.88), and 2.07 (1.48
      2.89) (P<.001 for trend). Increased risk was observed in all antibiotic classes
      studied and in a subanalysis having breast cancer fatality as the outcome. Among
      women with the highest levels of tetracycline or macrolide use, risk of breast
      cancer was not elevated in those using these antibiotics exclusively for acne or
      rosacea (indications that could be risk factors for breast cancer due to altered
      hormone levels), compared with those using them exclusively for respiratory tract
      infections, adjusted for age and length of enrollment (odds ratio, 0.91; 95%
      confidence interval, 0.44-1.87). CONCLUSIONS: Use of antibiotics is associated
      with increased risk of incident and fatal breast cancer. It cannot be determined
      from this study whether antibiotic use is causally related to breast cancer, or
      whether indication for use, overall weakened immune function, or other factors
      are pertinent underlying exposures. Although further studies are needed, these
      findings reinforce the need for prudent long-term use of antibiotics.

PMID- 14970062
TI  - NIH peer review of grant applications for clinical research.
AB  - CONTEXT: Support of research to facilitate translation of scientific discoveries
      to the prevention and treatment of human disease is a high priority for the US
      National Institutes of Health (NIH). Nevertheless, a perception exists among
      clinical investigators that the NIH peer review process may discriminate against
      clinical research. OBJECTIVE: To describe recent trends and outcomes of peer
      review of grant applications to NIH requesting support for clinical research.
      DESIGN AND SETTING: Peer review outcomes of grant applications submitted to NIH
      by MDs were compared with those of non-MDs, and outcomes of applications
      involving inclusion of human subjects were compared with those not involving
      human subjects. Analyses were carried out using an inclusive definition of
      clinical research and after stratifying clinical research into specific
      categories. MAIN OUTCOME MEASURES: Median priority scores and funding rates.
      RESULTS: Between 1997 and 2002, on average, 25.2% of total grant applications
      (ranging from 27 607 to 34 422 per year) were submitted by MDs, and 27.5% of
      awards (ranging from 8495 to 10 769 awards per year) were made to MDs. Median
      priority scores (239.0 vs 250.0) and funding rates (31.4% vs 29.1%) reviewed in 2
      grant cycles in 2002 were more favorable for MDs than for non-MDs (P<.001).
      However, median priority scores (254.0 vs 244.0) and funding rates (23.9% vs
      28.1%) were less favorable (P<.001) for R01 applications for clinical research (n
      = 7227 applications) than for nonclinical research (n = 10 209). This trend was
      most convincingly observed for clinical research categorized as mechanisms of
      disease (P =.006) or clinical trials and interventions (P =.001). Similar trends
      were observed for grant mechanisms other than R01. Concerns about safety and
      privacy of human subjects may have contributed to the less favorable outcomes of
      clinical research applications. CONCLUSION: Although physicians compete favorably
      in the peer review process, review outcomes are modestly less favorable for grant
      applications for clinical research than for laboratory research.

PMID- 14970063
TI  - Predictors of new-onset kidney disease in a community-based population.
AB  - CONTEXT: Kidney disease is associated with an increased risk for the development
      of cardiovascular disease and end-stage renal disease; however, risk factors for
      kidney disease have not been well studied. OBJECTIVE: To identify predictors of
      the development of new-onset kidney disease. DESIGN, SETTING, AND PARTICIPANTS: A
      community-based, longitudinal cohort study of 2585 participants who attended both
      a baseline examination in 1978-1982 and a follow-up examination in 1998-2001, and
      who were free of kidney disease at baseline. MAIN OUTCOME MEASURES: Kidney
      disease was assessed by the Modification of Diet in Renal Disease Study equation
      and defined by a glomerular filtration rate (GFR) in the fifth or lower
      percentile (< or =59.25 mL/min per 1.73 m2 in women, < or =64.25 mL/min per 1.73
      m2 in men). Stepwise logistic regression was used to determine the impact of risk
      factors on the occurrence of new-onset kidney disease. Baseline and long-term, 12
      year, averaged risk factor models were explored. RESULTS: At baseline, there were
      1223 men and 1362 women, with a mean age of 43 years, who were free of
      preexisting kidney disease. After a mean follow-up of 18.5 years, 244
      participants (9.4%) had developed kidney disease. In multivariable models,
      baseline age (odds ratio [OR], 2.36 per 10-year increment; 95% confidence
      interval [CI], 2.00-2.78), GFR (<90 mL/min per 1.73 m2: OR, 3.01; 95% CI, 1.98
      4.58; 90-119 mL/min per 1.73 m2: OR, 1.84; 95% CI, 1.16-2.93), body mass index
      (OR, 1.23 per 1 SD; 95% CI, 1.08-1.41), diabetes (OR, 2.60; 95% CI, 1.44-4.70),
      and smoking (OR, 1.42; 95% CI, 1.06-1.91) were related to the development of
      kidney disease. In addition to baseline age and GFR, the long-term, averaged risk
      factors that were predictive of kidney disease included hypertension (OR, 1.57;
      95% CI, 1.17-2.12), high-density lipoprotein cholesterol level (OR, 0.80 per 1
      SD; 95% CI, 0.69-0.92), and diabetes (OR, 2.38; 95% CI, 1.45-3.92). Compared with
      a normal GFR (> or =120 mL/min per 1.73 m2), a mildly reduced GFR (<90 mL/min per
      1.73 m2) predicted a 3-fold odds of progression to kidney disease (OR, 2.95; 95%
      CI, 1.94-4.49). CONCLUSIONS: Established cardiovascular disease risk factors are
      associated with the development of new-onset kidney disease. Patients with a
      mildly reduced GFR should be monitored for progression to kidney disease.

PMID- 14970064
TI  - Effectiveness over time of varicella vaccine.
AB  - CONTEXT: Reports of outbreaks of varicella in highly immunized groups have
      increased concern about the effectiveness of varicella vaccine. OBJECTIVE: To
      assess whether the effectiveness of varicella vaccine is affected either by time
      since vaccination or by age at the time of vaccination. DESIGN: Case-control
      study conducted from March 1997 through June 2003. SETTING: Twenty different
      group practices in southern Connecticut. PARTICIPANTS: Case subjects, identified
      by active surveillance of all practices, consisted of 339 eligible children 13
      months or older who were clinically diagnosed as having chickenpox and who also
      had a polymerase chain reaction (PCR) test result that was positive for varicella
      zoster virus DNA. For each case subject, 2 controls were selected, matched by
      both age and pediatric practice. MAIN OUTCOME MEASURES: The effectiveness of the
      vaccine, especially the effects of time since vaccination and age at the time of
      vaccination, adjusted for possible confounders. RESULTS: Although the adjusted
      overall effectiveness of the vaccine was 87% (95% confidence interval, 81%-91%;
      P<.001), there was a substantial difference in the vaccine's effectiveness in the
      first year after vaccination (97%) and in years 2 to 8 after vaccination (84%, P
      =.003). The vaccine's effectiveness in year 1 was substantially lower if the
      vaccine was administered at younger than 15 months (73%) than if it was
      administered at 15 months or older (99%, P =.01), although the difference in
      effectiveness overall for children immunized at younger than 15 months was not
      statistically significantly different than for those immunized at 15 months or
      older (81% vs 88%, P =.17). Most cases of chickenpox in vaccinees were mild.
      CONCLUSIONS: Although varicella vaccine is effective, its effectiveness decreases
      significantly after 1 year, although most cases of breakthrough disease are mild.
      If administered at younger than 15 months, the vaccine's effectiveness was lower
      in the first year after vaccination, but the difference in effectiveness was not
      statistically significant for subsequent years.

PMID- 14970065
TI  - Content and ratings of teen-rated video games.
AB  - CONTEXT: Children's exposure to violence, blood, sexual themes, profanity,
      substances, and gambling in the media remains a source of public health concern.
      However, content in video games played by older children and adolescents has not
      been quantified or compared with the rating information provided to consumers by
      the Entertainment Software Rating Board (ESRB). OBJECTIVES: To quantify and
      characterize the content in video games rated T (for "Teen") and to measure the
      agreement between the content observed in game play and the ESRB-assigned content
      descriptors displayed on the game box. DESIGN AND SETTING: We created a database
      of all 396 T-rated video game titles released on the major video game consoles in
      the United States by April 1, 2001, to identify the distribution of games by
      genre and to characterize the distribution of ESRB-assigned content descriptors.
      We randomly sampled 80 video game titles (which included 81 games because 1 title
      included 2 separate games), played each game for at least 1 hour, quantitatively
      assessed the content, and compared the content we observed with the content
      descriptors assigned by the ESRB. MAIN OUTCOME MEASURES: Depictions of violence,
      blood, sexual themes, gambling, and alcohol, tobacco, or other drugs; whether
      injuring or killing characters is rewarded or is required to advance in the game;
      characterization of gender associated with sexual themes; and use of profanity in
      dialogue, lyrics, or gestures. RESULTS: Analysis of all content descriptors
      assigned to the 396 T-rated video game titles showed 373 (94%) received content
      descriptors for violence, 102 (26%) for blood, 60 (15%) for sexual themes, 57
      (14%) for profanity, 26 (7%) for comic mischief, 6 (2%) for substances, and none
      for gambling. In the random sample of 81 games we played, we found that 79 (98%)
      involved intentional violence for an average of 36% of game play, 73 (90%)
      rewarded or required the player to injure characters, 56 (69%) rewarded or
      required the player to kill, 34 (42%) depicted blood, 22 (27%) depicted sexual
      themes, 22 (27%) contained profanity, 12 (15%) depicted substances, and 1 (1%)
      involved gambling. Our observations of 81 games match the ESRB content
      descriptors for violence in 77 games (95%), for blood in 22 (27%), for sexual
      themes in 16 (20%), for profanity in 14 (17%), and for substances in 1 (1%).
      Games were significantly more likely to depict females partially nude or engaged
      in sexual behaviors than males. Overall, we identified 51 observations of content
      that could warrant a content descriptor in 39 games (48%) in which the ESRB had
      not assigned a content descriptor. We found that the ESRB assigned 7 content
      descriptors for 7 games (9%) in which we did not observe the content indicated
      within 1 hour of game play. CONCLUSIONS: Content analysis suggests a significant
      amount of content in T-rated video games that might surprise adolescent players
      and their parents given the presence of this content in games without ESRB
      content descriptors. Physicians and parents should be aware that popular T-rated
      video games may be a source of exposure to a wide range of unexpected content.

PMID- 14970066
TI  - Initial misdiagnosis and outcome after subarachnoid hemorrhage.
AB  - CONTEXT: Mortality and morbidity can be reduced if aneurysmal subarachnoid
      hemorrhage (SAH) is treated urgently. OBJECTIVE: To determine the association of
      initial misdiagnosis and outcome after SAH. DESIGN, SETTING, AND PARTICIPANTS:
      Inception cohort of 482 SAH patients admitted to a tertiary care urban hospital
      between August 1996 and August 2001. MAIN OUTCOME MEASURES: Misdiagnosis was
      defined as failure to correctly diagnose SAH at a patient's initial contact with
      a medical professional. Functional outcome was assessed at 3 and 12 months with
      the modified Rankin Scale; quality of life (QOL), with the Sickness Impact
      Profile. RESULTS: Fifty-six patients (12%) were initially misdiagnosed, including
      42 of 221 (19%) of those with normal mental status at first contact. Migraine or
      tension headache (36%) was the most common incorrect diagnosis, and failure to
      obtain a computed tomography (CT) scan was the most common diagnostic error
      (73%). Neurologic complications occurred in 22 patients (39%) before they were
      correctly diagnosed, including 12 patients (21%) who experienced rebleeding.
      Normal mental status, small SAH volume, and right-sided aneurysm location were
      independently associated with misdiagnosis. Among patients with normal mental
      status at first contact, misdiagnosis was associated with worse QOL at 3 months
      and an increased risk of death or severe disability at 12 months. CONCLUSIONS: In
      this study, misdiagnosis of SAH occurred in 12% of patients and was associated
      with a smaller hemorrhage and normal mental status. Among individuals who
      initially present in good condition, misdiagnosis is associated with increased
      mortality and morbidity. A low threshold for CT scanning of patients with mild
      symptoms that are suggestive of SAH may reduce the frequency of misdiagnosis.

PMID- 14970067
TI  - Is this patient dead, vegetative, or severely neurologically impaired? Assessing
      outcome for comatose survivors of cardiac arrest.
AB  - CONTEXT: Most survivors of cardiac arrest are comatose after resuscitation, and
      meaningful neurological recovery occurs in a small proportion of cases. Treatment
      can be lengthy, expensive, and often difficult for families and caregivers.
      Physical examination is potentially useful in this clinical scenario, and the
      information obtained may help physicians and families make accurate decisions
      about treatment and/or withdrawal of care. OBJECTIVE: To determine the precision
      and accuracy of the clinical examination in predicting poor outcome in post
      cardiac arrest coma. DATA SOURCES AND STUDY SELECTION: We searched MEDLINE for
      English-language articles (1966-2003) using the terms coma, cardiac arrest,
      prognosis, physical examination, sensitivity and specificity, and observer
      variation. Other sources came from bibliographies of retrieved articles and
      physical examination textbooks. Studies were included if they assessed the
      precision and accuracy of the clinical examination in prognosis of post-cardiac
      arrest coma in adults. Eleven studies, involving 1914 patients, met our inclusion
      criteria. DATA EXTRACTION: Two authors independently reviewed each study to
      determine eligibility, abstract data, and classify methodological quality using
      predetermined criteria. Disagreement was resolved by consensus. DATA SYNTHESIS:
      Summary likelihood ratios (LRs) were calculated from random effects models. Five
      clinical signs were found to strongly predict death or poor neurological outcome:
      absent corneal reflexes at 24 hours (LR, 12.9; 95% confidence interval [CI], 2.0
      68.7), absent pupillary response at 24 hours (LR, 10.2; 95% CI, 1.8-48.6), absent
      withdrawal response to pain at 24 hours (LR, 4.7; 95% CI, 2.2-9.8), no motor
      response at 24 hours (LR, 4.9; 95% CI, 1.6-13.0), and no motor response at 72
      hours (LR, 9.2; 95% CI, 2.1-49.4). The proportion of individuals' dying or having
      a poor neurological outcome was calculated by pooling the outcome data from the
      11 studies (n = 1914) and used as an estimate of the pretest probability of poor
      outcome. The random effects estimate of poor outcome was 77% (95% CI, 72%-80%).
      The highest LR increases the pretest probability of 77% to a posttest probability
      of 97% (95% CI, 87%-100%). No clinical findings were found to have LRs that
      strongly predicted good neurological outcome. CONCLUSIONS: Simple physical
      examination maneuvers strongly predict death or poor outcome in comatose
      survivors of cardiac arrest. The most useful signs occur at 24 hours after
      cardiac arrest, and earlier prognosis should not be made by clinical examination
      alone. These data provide prognostic information, rather than treatment
      recommendations, which must be made on an individual basis incorporating many
      other variables.

PMID- 14970068
TI  - Antibiotics and breast cancer--what's the meaning of this?

PMID- 14970069
TI  - The clinical researcher--an "emerging" species.

PMID- 14970070
TI  - JAMA patient page. Chickenpox.

PMID- 14970071
TI  - The "file drawer" phenomenon: suppressing clinical evidence.

PMID- 14970074
TI  - Penny wise, pound foolish.

PMID- 14970075
TI  - SARS respiratory protection: update.

PMID- 14970076
TI  - Does experience or delivery volume of family physicians predict maternal and
      newborn outcomes?

PMID- 14970077
TI  - Anticoagulation.

PMID- 14970078
TI  - Anticoagulation.

PMID- 14970079
TI  - Anticoagulation.

PMID- 14970081
TI  - Anticoagulation.

PMID- 14970082
TI  - UK psychiatrists question SSRI warnings for under-18s.

PMID- 14970083
TI  - Martin government to reintroduce patent changes.

PMID- 14970085
TI  - Albertans' health records go online despite concerns.

PMID- 14970086
TI  - Factors contributing to obesity in adolescents.

PMID- 14970088
TI  - US Medicare reform: why drug companies and private insurers are smiling.

PMID- 14970089
TI  - Age-related macular degeneration: armed against ARMD.

PMID- 14970091
TI  - A 47-year-old man with mesothelioma and neck swelling.

PMID- 14970092
TI  - What factors are associated with decisions to withdraw mechanical ventilation in
      the intensive care unit?

PMID- 14970093
TI  - Optimal duration of antibiotic therapy for uncomplicated urinary tract infection
      in older women: a double-blind randomized controlled trial.
AB  - BACKGROUND: The optimal duration of antibiotic therapy in older patients with
      uncomplicated urinary tract infection (UTI) is still a matter of debate. The aim
      of this randomized controlled double-blind noninferiority trial was to compare
      the efficacy and safety of 3-day and 7-day courses of oral ciprofloxacin for
      uncomplicated symptomatic UTI in older women. METHODS: A total of 183 women at
      least 65 years of age with acute uncomplicated UTI were recruited from ambulatory
      clinics and hospital acute care units. Patients with pyelonephritis,
      contraindications to fluoroquinolones, recent use of antibiotics, urinary tract
      abnormalities and diabetes mellitus were excluded. Women were randomly assigned
      to receive either ciprofloxacin 250 mg twice daily orally for 3 days followed by
      placebo for 4 days (the 3-day group, 93 patients) or ciprofloxacin 250 mg twice
      daily orally for 7 days (the 7-day group, 90 patients). Bacterial eradication,
      clinical improvement and occurrence of adverse events were determined 2 days
      after completion of treatment, and occurrence of reinfection or relapse were
      determined 6 weeks after completion of treatment. Bacterial eradication and
      relapse were determined by urine culture. Double-blind procedures were maintained
      throughout data collection. RESULTS: The proportion of patients with bacterial
      eradication at 2 days after treatment was 98% (91/93) in the 3-day group and 93%
      (83/89) in the 7-day group (p = 0.16). The frequency of adverse events, including
      drowsiness, headache, nausea or vomiting, and loss of appetite, was significantly
      lower in the 3-day group. INTERPRETATION: These results suggest that a 3-day
      course of antibiotic therapy is not inferior to a 7-day course for treatment of
      uncomplicated symptomatic UTI in older women, and that the shorter course is
      better tolerated.

PMID- 14970094
TI  - Association between industry funding and statistically significant pro-industry
      findings in medical and surgical randomized trials.
AB  - BACKGROUND: Conflicting reports exist in the medical literature regarding the
      association between industry funding and published research findings. In this
      study, we examine the association between industry funding and the statistical
      significance of results in recently published medical and surgical trials.
      METHODS: We examined a consecutive series of 332 randomized trials published
      between January 1999 and June 2001 in 8 leading surgical journals and 5 medical
      journals. Each eligible study was independently reviewed for methodological
      quality using a 21-point index with 5 domains: randomization, outcomes,
      eligibility criteria, interventions and statistical issues. Our primary analysis
      included studies that explicitly identified the primary outcome and reported it
      as statistically significant. For studies that did not explicitly identify a
      primary outcome, we defined a "positive" study as one with at least 1
      statistically significant outcome measure. We used multivariable regression
      analysis to determine whether there was an association between reported industry
      funding and trial results, while controlling for study quality and sample size.
      RESULTS: Among the 332 randomized trials, there were 158 drug trials, 87 surgical
      trials and 87 trials of other therapies. In 122 (37%) of the trials, authors
      declared industry funding. An unadjusted analysis of this sample of trials
      revealed that industry funding was associated with a statistically significant
      result in favour of the new industry product (odds ratio [OR] 1.9, 95% confidence
      interval [CI] 1.3-3.5). The association remained significant after adjustment for
      study quality and sample size (adjusted OR 1.8, 95% CI 1.1-3.0). There was a
      nonsignificant difference between surgical trials (OR 8.0, 95% CI 1.1-53.2) and
      drug trials (OR 1.6, 95% CI 1.1-2.8), both of which were likely to have a pro
      industry result (relative OR 5.0, 95% CI 0.7-37.5, p = 0.14). INTERPRETATION:
      Industry-funded trials are more likely to be associated with statistically
      significant pro-industry findings, both in medical trials and surgical
      interventions.

PMID- 14970095
TI  - Randomized clinical trials: what gets published, and when?

PMID- 14970096
TI  - Antidepressants and adverse effects in young patients: uncovering the evidence.

PMID- 14970097
TI  - Facing the evidence: antidepressant treatment in children and adolescents.

PMID- 14970098
TI  - Dracunculiasis (guinea worm disease).
AB  - Dracunculiasis (guinea worm disease) is a parasitic disease that is limited to
      remote, rural villages in 13 sub-Saharan African countries that do not have
      access to safe drinking water. It is one the next diseases targeted for
      eradication by the World Health Organization. Guinea worm disease is transmitted
      by drinking water containing copepods (water fleas) that are infected with
      Dracunculiasis medinensis larvae. One year after human ingestion of infected
      water a female adult worm emerges, typically from a lower extremity, producing
      painful ulcers that can impair mobility for up to several weeks. This disease
      occurs annually when agricultural activities are at their peak. Large proportions
      of economically productive individuals of a village are usually affected
      simultaneously, resulting in decreased agricultural productivity and economic
      hardship. Eradication of guinea worm disease depends on prevention, as there is
      no effective treatment or vaccine. Since 1986, there has been a 98% reduction in
      guinea worm disease worldwide, achieved primarily through community-based
      programs. These programs have educated local populations on how to filter
      drinking water to remove the parasite and how to prevent those with ulcers from
      infecting drinking-water sources. Complete eradication will require sustained
      high-level political, financial and community support.

PMID- 14970103
TI  - We must use the knowledge that we have to treat patients with acute coronary
      syndromes.

PMID- 14970104
TI  - Clinical importance of obesity versus the metabolic syndrome in cardiovascular
      risk in women: a report from the Women's Ischemia Syndrome Evaluation (WISE)
      study.
AB  - BACKGROUND: Obesity and the metabolic syndrome frequently coexist. Both are
      associated with cardiovascular disease (CVD). However, the contribution of
      obesity to cardiovascular risk, independent of the presence of the metabolic
      syndrome, remains controversial. METHODS AND RESULTS: From the WISE study, 780
      women referred for coronary angiography to evaluate suspected myocardial ischemia
      were classified by body mass index (BMI; <24.9=normal, n=184; > or =25.0 to < or
      =29.9=overweight, n=269; > or =30.0=obese, n=327) and presence (n=451) or absence
      (n=329) of the metabolic syndrome, further classified by diabetes status.
      Prevalence of significant angiographic coronary artery disease (CAD; > or =50%
      stenosis) and 3-year risk of CVD were compared by BMI and metabolic status. The
      metabolic syndrome and BMI were strongly associated, but only metabolic syndrome
      was associated with significant CAD. Similarly, unit increases in BMI (normal to
      overweight to obese) were not associated with 3-year risk of death (adjusted
      hazard ratio [HR] 0.92, 95% CI 0.59 to 1.51) or major adverse cardiovascular
      event (MACE: death, nonfatal myocardial infarction, stroke, congestive heart
      failure; adjusted HR 0.95, 95% CI 0.71 to 1.27), whereas metabolic status (normal
      to metabolic syndrome to diabetes) conferred an approximate 2-fold adjusted risk
      of death (HR 2.01, 95% CI 1.26 to 3.20) and MACE (HR 1.88, 95% CI 1.38 to 2.57).
      Levels of C-reactive protein (hs-CRP) were more strongly associated with
      metabolic syndrome than BMI but were not independently associated with 3-year
      risk of death or MACE. CONCLUSIONS: The metabolic syndrome but not BMI predicts
      future cardiovascular risk in women. Although it remains prudent to recommend
      weight loss in overweight and obese women, control of all modifiable risk factors
      in both normal and overweight persons to prevent transition to the metabolic
      syndrome should be considered the ultimate goal.

PMID- 14970105
TI  - Metabolic syndrome modifies the cardiovascular risk associated with angiographic
      coronary artery disease in women: a report from the Women's Ischemia Syndrome
      Evaluation.
AB  - BACKGROUND: The metabolic syndrome, which is characterized by a constellation of
      fasting hyperglycemia, hypertriglyceridemia, low HDL cholesterol, hypertension,
      and/or abdominal obesity, is a risk factor for the development of coronary artery
      disease (CAD) and cardiovascular events. The interrelationship between metabolic
      status and CAD on cardiovascular risk in women is not known. METHODS AND RESULTS:
      We evaluated interrelationships between angiographic CAD, the metabolic syndrome,
      and incident cardiovascular events among 755 women from the Women's Ischemia
      Syndrome Evaluation (WISE) study who were referred for coronary angiography to
      evaluate suspected myocardial ischemia; 25% of the cohort had the metabolic
      syndrome at study entry. Compared with women with normal metabolic status, women
      with the metabolic syndrome had a significantly lower 4-year survival rate (94.3%
      versus 97.8%, P=0.03) and event-free survival from major adverse cardiovascular
      events (death, nonfatal myocardial infarction, stroke, or congestive heart
      failure; 87.8% versus 93.5%, P=0.003). When the subjects were stratified by the
      presence or absence of angiographically significant CAD at study entry, in women
      with angiographically significant CAD, the metabolic syndrome resulted in
      significantly higher risk of cardiovascular events than in women with normal
      metabolic status (hazard ratio 4.93, 95% CI 1.02 to 23.76; P=0.05), whereas it
      did not result in increased 4-year cardiovascular risk in women without
      angiographically significant CAD (hazard ratio 1.41, 95% CI 0.32 to 6.32;
      P=0.65). CONCLUSIONS: These data suggest that in women with suspected myocardial
      ischemia, the metabolic syndrome modifies the cardiovascular risk associated with
      angiographic CAD. Specifically, the metabolic syndrome was found to be a
      predictor of 4-year cardiovascular risk only when associated with significant
      angiographic CAD.

PMID- 14970106
TI  - Abnormal coronary vasomotion as a prognostic indicator of cardiovascular events
      in women: results from the National Heart, Lung, and Blood Institute-Sponsored
      Women's Ischemia Syndrome Evaluation (WISE).
AB  - BACKGROUND: Coronary vascular dysfunction has been linked to atherosclerosis and
      adverse cardiovascular outcomes in men, but these relationships have not been
      firmly established in women. METHODS AND RESULTS: As part of the Women's Ischemia
      Syndrome Evaluation (WISE) sponsored by the National Heart, Lung, and Blood
      Institute, 163 women referred for clinically indicated coronary angiography
      underwent coronary reactivity assessment with quantitative coronary angiography
      and intracoronary Doppler flow before and after intracoronary administration of
      acetylcholine, adenosine, and nitroglycerin and were then followed up for
      clinical outcomes. History of hypertension was present in 61%, dyslipidemia in
      54%, diabetes in 26%, and current tobacco use in 21% of women enrolled. Seventy
      five percent had no or only mild epicardial coronary artery disease (CAD). Over a
      median follow-up of 48 months, events occurred in 58 women. On bivariate
      analysis, women with an event had significantly less change in coronary cross
      sectional area (DeltaCSA) in response to acetylcholine (P=0.0006) and
      nitroglycerin (P=0.04). In addition, women with abnormal coronary dilator
      response to acetylcholine had less time free from cardiovascular events
      (P=0.004). In multivariable analysis, after controlling for age, hypertension,
      diabetes, dyslipidemia, tobacco use, and CAD severity, %DeltaCSA with
      acetylcholine (P=0.001) independently predicted events. When the outcome was
      restricted to only death, myocardial infarction, congestive heart failure, and
      stroke, %DeltaCSA with acetylcholine remained a significant predictor (P=0.006).
      CONCLUSIONS: In women in this study, impaired coronary vasomotor response to
      acetylcholine was independently linked to adverse cardiovascular outcomes
      regardless of CAD severity.

PMID- 14970107
TI  - Serum amyloid A as a predictor of coronary artery disease and cardiovascular
      outcome in women: the National Heart, Lung, and Blood Institute-Sponsored Women's
      Ischemia Syndrome Evaluation (WISE).
AB  - BACKGROUND: Serum amyloid-alpha (SAA) is a sensitive marker of an acute
      inflammatory state. Like high-sensitivity C-reactive protein (hs-CRP), SAA has
      been linked to atherosclerosis. However, prior studies have yielded inconsistent
      results, and the independent predictive value of SAA for coronary artery disease
      (CAD) severity and cardiovascular events remains unclear. METHODS AND RESULTS: A
      total of 705 women referred for coronary angiography for suspected myocardial
      ischemia underwent plasma assays for SAA and hs-CRP, quantitative angiographic
      assessment, and follow-up evaluation. Cardiovascular events were death,
      myocardial infarction, congestive heart failure, stroke, and other vascular
      events. The women's mean age was 58 years (range 21 to 86 years), and 18% were
      nonwhite. SAA and hs-CRP were associated with a broad range of CAD risk factors.
      After adjustment for these risk factors, SAA levels were independently but
      moderately associated with angiographic CAD (P=0.004 to 0.04) and highly
      predictive of 3-year cardiovascular events (P<0.0001). By comparison, hs-CRP was
      not associated with angiographic CAD (P=0.08 to 0.35) but, like SAA, was strongly
      and independently predictive of adverse cardiovascular outcome (P<0.0001).
      CONCLUSIONS: Our results show a strong independent relationship between SAA and
      future cardiovascular events, similar to that found for hs-CRP. Although SAA was
      independently but moderately associated with angiographic CAD, this association
      was not found for hs-CRP. These results are consistent with the hypothesis that
      systemic inflammation, manifested by high SAA or hs-CRP levels, may promote
      atherosclerotic plaque destabilization, in addition to exerting a possible direct
      effect on atherogenesis.

PMID- 14970108
TI  - Relationship of high and low ankle brachial index to all-cause and cardiovascular
      disease mortality: the Strong Heart Study.
AB  - BACKGROUND: The associations of low (<0.90) and high (>1.40) ankle brachial index
      (ABI) with risk of all-cause and cardiovascular disease (CVD) mortality have not
      been examined in a population-based setting. METHODS AND RESULTS: We examined all
      cause and CVD mortality in relation to low and high ABI in 4393 American Indians
      in the Strong Heart Study. Participants had bilateral ABI measurements at
      baseline and were followed up for 8.3+/-2.2 years (36 589 person-years). Cox
      regression was used to quantify mortality rates among participants with high and
      low ABI relative to those with normal ABI (0.90 < or =ABI < or =1.40). Death from
      all causes occurred in 1022 participants (23.3%; 27.9 deaths per 1000 person
      years), and of these, 272 (26.6%; 7.4 deaths per 1000 person-years) were
      attributable to CVD. Low ABI was present in 216 participants (4.9%), and high ABI
      occurred in 404 (9.2%). Diabetes, albuminuria, and hypertension occurred with
      greater frequency among persons with low (60.2%, 44.4%, and 50.1%) and high
      (67.8%, 49.9%, and 45.1%) ABI compared with those with normal ABI (44.4%, 26.9%,
      and 36.5%), respectively (P<0.0001). Adjusted risk estimates for all-cause
      mortality were 1.69 (1.34 to 2.14) for low and 1.77 (1.48 to 2.13) for high ABI,
      and estimates for CVD mortality were 2.52 (1.74 to 3.64) for low and 2.09 (1.49
      to 2.94) for high ABI. CONCLUSIONS: The association between high ABI and
      mortality was similar to that of low ABI and mortality, highlighting a U-shaped
      association between this noninvasive measure of peripheral arterial disease and
      mortality risk. Our data suggest that the upper limit of normal ABI should not
      exceed 1.40.

PMID- 14970109
TI  - Patients with type 3 severe von Willebrand disease are not protected against
      atherosclerosis: results from a multicenter study in 47 patients.
AB  - BACKGROUND: The results of a number of studies in pigs and mice suggest that
      absence of von Willebrand factor (vWF) protects against the development of
      atherosclerosis. We studied whether patients with a complete deficiency of vWF
      (type 3 von Willebrand disease [vWD]) develop fewer atherosclerotic vessel wall
      changes than healthy controls. METHODS AND RESULTS: This study included 47
      individuals with type 3 vWD and 84 healthy controls. Early atherosclerotic
      changes were assessed by measuring the thickness of the intima-media in the
      carotid and femoral arteries by B-mode ultrasonography. Advanced atherosclerotic
      changes were quantified by summing the maximal thickness of atherosclerotic
      plaques in the carotid and femoral arteries and were expressed as a plaque score.
      Established risk factors were determined to adjust for possible differences
      between the groups. We found no substantial difference in intima-media thickness
      between vWD patients and controls (adjusted difference for carotid artery 0.007
      mm, 95% CI -0.022 to 0.036 mm; femoral artery 0.069 mm, 95% CI -0.056 to 0.19
      mm). Similar proportions of patients and controls had atherosclerotic plaques
      (19% and 17%, respectively). No difference was found in the plaque score between
      groups (adjusted difference -0.22 mm, 95% CI -0.69 to 0.26). Among vWD patients,
      we found no effect of treatment with vWF concentrates on intima-media thickness
      or plaque score. CONCLUSIONS: The results of this study indicate that vWF does
      not play a substantial role in human atherogenesis.

PMID- 14970110
TI  - Impact of combination evidence-based medical therapy on mortality in patients
      with acute coronary syndromes.
AB  - BACKGROUND: Several individual pharmacological agents, such as antiplatelet
      drugs, beta-blockers, ACE inhibitors, and lipid-lowering agents, have proven
      efficacy in reducing mortality in patients with acute coronary syndromes.
      However, the impact of the combination of these agents on clinical outcomes has
      not been studied before. METHODS AND RESULTS: A total of 1358 consecutive
      patients presenting with acute coronary syndromes between January 1999 and March
      2002 were identified, and data on baseline demographics, comorbidities, and in
      hospital management were collected. On the basis of discharge use of evidence
      based therapies, we created a composite appropriateness score depending on the
      number of the drugs used divided by the number of the drugs potentially indicated
      for each patient. The impact of the composite score on 6-month mortality was
      analyzed using a risk-adjusted logistic regression model. The odds ratio for
      death for all indicated medications used (appropriateness level IV) versus none
      of the indicated medications used (appropriateness level 0) was 0.10 (95% CI,
      0.03 to 0.42; P<0.0001); similarly, odds ratio for appropriateness level III
      versus level 0 was 0.17 (95% CI, 0.04 to 0.75; P=0.0018), odds ratio for
      appropriateness level II versus level 0 was 0.18 (95% CI, 0.04 to 0.77; P=0.01),
      and odds ratio for appropriateness level I versus level 0 was 0.36 (95% CI, 0.08
      to 1.75; P=0.20). CONCLUSIONS: Use of combination evidence-based medical
      therapies was independently and strongly associated with lower 6-month mortality
      in patients with acute coronary syndromes. Such therapies, most of which are
      generic and inexpensive today, seem to offer a marked survival advantage compared
      with patients in whom such therapies are omitted.

PMID- 14970111
TI  - Therapy of ischemic cardiomyopathy with the immunomodulating agent
      pentoxifylline: results of a randomized study.
AB  - BACKGROUND: Inflammatory immune activation commonly occurs in heart failure and
      may perpetuate this syndrome. We sought to determine whether the immunomodulating
      agent pentoxifylline enhances left ventricular function in patients with ischemic
      cardiomyopathy. We also investigated the effect of therapy on levels of brain
      natriuretic peptide (NT-pro BNP), C-reactive protein (CRP), tumor necrosis factor
      alpha (TNF-alpha), and the marker of apoptosis, Fas/Apo-1. METHODS AND RESULTS:
      In a single-center, prospective, randomized, double-blind, placebo-controlled
      study, 38 patients with ischemic cardiomyopathy received pentoxifylline 400 mg
      TID or placebo in addition to standard therapy. Clinical assessment, radionuclide
      ventriculography, echocardiography, and blood analyses were performed at baseline
      and after 6 months. There were no differences in baseline characteristics between
      the groups. Five patients died (4 in the placebo group). Pentoxifylline treatment
      resulted in an improvement in functional class (P<0.005) and an increase in
      systolic blood pressure (P<0.05) and left ventricular radionuclide ejection
      fraction (P<0.05) compared with the placebo-treated group. There were reductions
      in plasma concentrations of CRP, NT-pro BNP, TNF-alpha, and Fas/Apo-1 in the
      pentoxifylline compared with the placebo-treated group. CONCLUSIONS: In patients
      with heart failure due to ischemic left ventricular dysfunction, the addition of
      pentoxifylline to standard therapy results in improvements in clinical status and
      radionuclide ejection fraction, which are accompanied by reductions in plasma
      markers of inflammation, prognosis, and apoptosis.

PMID- 14970112
TI  - Single-wire pressure and flow velocity measurement to quantify coronary stenosis
      hemodynamics and effects of percutaneous interventions.
AB  - BACKGROUND: Lack of high-fidelity simultaneous measurements of pressure and flow
      velocity distal to a coronary artery stenosis has hampered the study of stenosis
      pressure drop-velocity (DeltaP-v) relationships in patients. METHODS AND RESULTS:
      A novel 0.014-inch dual-sensor (pressure and Doppler velocity) guidewire was used
      in 15 coronary lesions to obtain per-beat averages of pressure drop and velocity
      after an intracoronary bolus of adenosine. DeltaP-v relations from resting to
      maximal hyperemic velocity were constructed before and after stepwise executed
      percutaneous coronary intervention (PCI). Before PCI, half of the DeltaP-v
      relations revealed the presence of a compliant stenosis, which was stabilized by
      angioplasty. Fractional flow reserve (FFR), coronary flow reserve (CFVR), and
      velocity-based indices of stenosis resistance (h-SRv) and microvascular
      resistance (h-MRv) at maximal hyperemia were compared. Stepwise PCI significantly
      lowered h-SRv, with an initial marked reduction in hyperemic pressure drop
      followed by further gains in velocity. A concomitant significant reduction of h
      MRv accounted for half of the gain in velocity after PCI. The average magnitude
      of absolute incremental hemodynamic changes was highest for h-SRv (56.8+/-39.2%)
      compared with CFVR (35.3+/-34.5%, P<0.005) or FFR (19.5+/-25.2%, P<0.0001).
      CONCLUSIONS: DeltaP-v relations comprehensively visualize improvements in
      coronary hemodynamics after PCI. h-SRv is a powerful and sensitive descriptor of
      the functional gain achieved by PCI, combining information about both pressure
      gradient and velocity, which are oppositely affected by PCI. Simultaneous
      assessment of stenosis and microvascular resistance may provide a valuable tool
      for guidance of PCI.

PMID- 14970113
TI  - Role of aortic root motion in the pathogenesis of aortic dissection.
AB  - BACKGROUND: The downward movement of the aortic root during the cardiac cycle may
      be responsible for producing the circumferential tear observed in aortic
      dissections. METHODS AND RESULTS: Contrast injections were investigated in 40
      cardiac patients, and a finite element model of the aortic root, arch, and
      branches of the arch was built to assess the influence of aortic root
      displacement and pressure on the aortic wall stress. The axial displacement of
      the aortic root ranged from 0 to 14 mm. It was increased in patients with aortic
      insufficiency (22+/-13% of the sino-tubular junction diameter versus 12+/-9%) and
      reduced in patients with hypokinesis of the left ventricle (10+/-9% of sino
      tubular junction versus 17+/-12%). The largest stress increase due to aortic root
      displacement was found approximately 2 cm above the sino-tubular junction, where
      the longitudinal stress increased by 50% to 0.32 Nmm(-2) when 8.9-mm axial
      displacement was applied in addition to 120-mm Hg luminal pressure. A similar
      result was observed when the pressure load was increased to 180 mm Hg without
      axial displacement. CONCLUSIONS: Both aortic root displacement and hypertension
      significantly increase the longitudinal stress in the ascending aorta. For
      patients with hypertension who are at risk of dissection, aortic root movement
      may be monitored as an important risk factor.

PMID- 14970114
TI  - Endoproteolytic activation of alpha(v) integrin by proprotein convertase PC5 is
      required for vascular smooth muscle cell adhesion to vitronectin and integrin
      dependent signaling.
AB  - BACKGROUND: Integrins play an important role for vascular smooth muscle cell
      (VSMC) migration during the development of atherosclerosis and restenosis.
      Integrin alpha(v)-subunit consists of disulphide-bound 125-kDa heavy and 25-kDa
      light chains, which are generated by endoproteolytic cleavage. This type of
      activation requires the presence of suitable proprotein convertases (PCs). Based
      on ex vivo and in vitro data, the PC5 isozyme has been suggested to be the major
      integrin convertase. We have recently demonstrated that PC5 is upregulated during
      vascular remodeling in rodents, colocalizing with alpha(v) in VSMCs. The aim of
      this study was to investigate the activation of alpha(v) by PCs in VSMCs and its
      consequences for alpha(v)-dependent cell functions. METHODS AND RESULTS:
      Immunoblotting demonstrated that inhibition of PC activity by the specific
      pharmacological inhibitor dec-CMK inhibits alpha(v) cleavage in VSMCs. These
      results were confirmed using PC5-specific antisense oligonucleotides. PC5
      antisense oligonucleotides and dec-CMK inhibited VSMC adhesion to the
      alpha(v)beta3/beta5 ligand vitronectin (both P<0.05). Furthermore, PC5-asODNs
      inhibited VSMC migration on vitronectin-coated wells (P<0.05). Inhibition of PC
      activity and consequently alpha(v) cleavage inhibited the adhesion-dependent
      focal adhesion kinase(Y397)-autophosphorylation and subsequent Akt activation,
      whereas phosphorylation of extracellular signal-regulated kinase 1/2 was not
      affected. In human endarterectomy lesions, PC5 colocalized with alpha(v) integrin
      in VSMCs in the atherosclerotic plaques. CONCLUSIONS: The present study
      demonstrates that alpha(v) endoproteolytic activation is necessary for integrin
      mediated adhesion and migration as well as signaling and requires PC5 in VSMCs.
      The colocalization of PC5 and alpha(v) in human carotid plaques indicates that
      PC5 might play a key role for alpha(v) activation in vivo.

PMID- 14970115
TI  - The neuropeptide secretoneurin acts as a direct angiogenic cytokine in vitro and
      in vivo.
AB  - BACKGROUND: Secretoneurin is an abundant neuropeptide of the central, peripheral,
      and autonomic nervous systems, located in nerve fibers characterized by a close
      interaction with blood vessels and known to stimulate endothelial cell migration.
      METHODS AND RESULTS: We hypothesized that secretoneurin might act as an
      angiogenic cytokine and tested for these effects in vivo using a mouse cornea
      neovascularization model and in vitro by assessing capillary tube formation in a
      matrigel assay. In vivo, secretoneurin-induced neovasculature is characterized by
      a distinct pattern of arterial and venous vessels of large diameter and length.
      Immunohistochemical staining for CD-31 revealed endothelial lining of the inner
      surface of these vessels, and recruitment of alpha-smooth muscle actin-positive
      perivascular cells suggests vessel maturation. In vitro, secretoneurin-induced
      capillary tube formation was dose dependent and specific, confirming that effects
      of secretoneurin occur directly on endothelial cells. Secretoneurin also
      stimulated proliferation and exerted antiapoptotic effects on endothelial cells
      and activated intracellular phosphatidylinositol 3' kinase/Akt and mitogen
      activated protein kinase pathways, as demonstrated by increased phosphorylation
      of Akt and extracellular signal-regulated kinase. CONCLUSIONS: These data show
      that secretoneurin represents a novel direct angiogenic cytokine and reiterate
      the coordinated relationship between nervous and vascular systems.

PMID- 14970116
TI  - Reduced myocardial ischemia-reperfusion injury in toll-like receptor 4-deficient
      mice.
AB  - BACKGROUND: Myocardial ischemia and reperfusion-induced tissue injury involve a
      robust inflammatory response, but the proximal events in reperfusion injury
      remain incompletely defined. Toll-like receptor 4 (TLR4) is a proximal signaling
      receptor in innate immune responses to lipopolysaccharide of Gram-negative
      pathogens. TLR4 is also expressed in the heart and vasculature, but a role for
      TLR4 in the myocardial response to injury separate from microbial pathogens has
      not been examined. This study assessed the role of TLR4 in myocardial infarction
      and inflammation in a murine model of ischemia-reperfusion injury. METHODS AND
      RESULTS: Myocardial ischemia-reperfusion (MIR) was performed on 2 strains of TLR4
      deficient mice (C57/BL10 ScCr and C3H/HeJ) and controls (C57/BL10 ScSn and
      C3H/OuJ). Mice were subjected to 1 hour of coronary ligation, followed by 24
      hours of reperfusion. TLR4-deficient mice sustained significantly smaller
      infarctions compared with control mice given similar areas at risk. Fewer
      neutrophils infiltrated the myocardium of TLR4-deficient Cr mice after MIR,
      indicated by less myeloperoxidase activity and fewer CD45/GR1-positive cells. The
      myocardium of TLR4-deficient Cr mice contained fewer lipid peroxides and less
      complement deposition compared with control mice after MIR. Serum levels of
      interleukin-12, interferon-gamma, and endotoxin were not increased after ischemia
      reperfusion. Neutrophil trafficking in the peritoneum was similar in all strains
      after injection of thioglycollate. CONCLUSIONS: TLR4-deficient mice sustain
      smaller infarctions and exhibit less inflammation after myocardial ischemia
      reperfusion injury. The data suggest that in addition to its role in innate
      immune responses, TLR4 serves a proinflammatory role in murine myocardial
      ischemia-reperfusion injury.

PMID- 14970117
TI  - Pitavastatin downregulates expression of the macrophage type B scavenger
      receptor, CD36.
AB  - BACKGROUND: Pitavastatin (NK-104) is a novel inhibitor of 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for
      cholesterol biosynthesis. In clinical trials, pitavastatin has been shown to
      significantly decrease serum LDL cholesterol and triglyceride levels and increase
      HDL cholesterol. Scavenger receptor-mediated accumulation of oxidized LDL (OxLDL)
      derived cholesteryl ester is considered to be a critical step in the development
      of atherosclerotic foam cell formation. We studied the effect of pitavastatin on
      CD36 (a class B scavenger receptor) expression by murine macrophages. METHODS AND
      RESULTS: Treatment of J774 cells and murine peritoneal macrophages with
      pitavastatin decreased CD36 mRNA expression in a dose-dependent manner. Decreased
      CD36 mRNA was associated with decreased CD36 cell surface protein expression in
      human THP-1 cells and human monocyte-derived macrophages. Pitavastatin also
      reduced the increase in CD36 mRNA, cell surface protein, and binding/uptake of
      OxLDL induced by peroxisome proliferator-activated receptor-gamma (PPARgamma)
      ligands and/or OxLDL. Pitavastatin did not alter the half-life of CD36 mRNA,
      which suggests pitavastatin downregulates CD36 expression by reducing CD36
      transcription. In addition, pitavastatin significantly decreased PPARgamma mRNA
      and protein expression. Finally, pitavastatin increased p44/42 mitogen-activated
      protein kinase activity and PPARgamma phosphorylation and increased the ratio of
      phosphorylated PPARgamma to nonphosphorylated PPARgamma. CONCLUSIONS: The present
      data demonstrate that pitavastatin prevents OxLDL uptake by macrophages through
      PPARgamma-dependent inhibition of CD36 expression and suggest that pitavastatin
      could modulate CD36-mediated atherosclerotic foam cell formation.

PMID- 14970118
TI  - Intramuscular gene transfer of soluble tumor necrosis factor-alpha receptor 1
      activates vascular endothelial growth factor receptor and accelerates
      angiogenesis in a rat model of hindlimb ischemia.
AB  - BACKGROUND: In a pathological setting, tumor necrosis factor (TNF)-alpha inhibits
      the proliferative response of endothelial cells through inactivation of receptors
      for vascular endothelial growth factor (VEGF). Soluble TNF-alpha receptor 1
      (sTNFR1) is an extracellular domain of TNFR1 and an antagonist to TNF-alpha. In
      the present study, we examined the effect of sTNFR1 expression plasmid on
      receptor for VEGF (KDR/flk-1) and angiogenesis in a rat model of hindlimb
      ischemia. METHODS AND RESULTS: The left femoral artery was exposed and excised to
      induce limb ischemia. A total of 400 microg of sTNFR1 or LacZ plasmid was
      injected into 3 different sites of the adductor muscle immediately after the
      induction of ischemia. TNF-alpha bioactivity in ischemic adductors increased in
      rats receiving LacZ plasmid compared with sham-operated rats. However, sTNFR1
      plasmid significantly suppressed the increase in TNF-alpha bioactivity. KDR/flk-1
      mRNA and tyrosine phosphorylation of KDR/flk-1 were significantly increased in
      the muscles injected with sTNFR1 plasmid compared with those injected with LacZ
      plasmid. VEGF increased both in muscles injected with sTNFR1 plasmid and in
      muscles injected with LacZ plasmid but did not differ significantly between them.
      At 21 days after the induction of ischemia, the sTNFR1 plasmid-transfected
      muscles showed significantly increased capillary density compared with LacZ
      plasmid-transfected muscles. CONCLUSIONS: In a rat model of hindlimb ischemia,
      VEGF increased but activation of KDR/flk-1 was suppressed, possibly by TNF-alpha,
      which might impair angiogenesis. Suppression of TNF-alpha with sTNFR1 plasmid
      upregulated KDR/flk-1 and accelerated angiogenesis. Local transfection of the
      sTNFR1 gene can be a new strategy for therapeutic angiogenesis in peripheral
      ischemic diseases.

PMID- 14970119
TI  - Images in cardiovascular medicine. Debris trapped by a distal protection device
      may mimic no-reflow during percutaneous coronary intervention.

PMID- 14970120
TI  - Women's Ischemic Syndrome Evaluation: current status and future research
      directions: report of the National Heart, Lung and Blood Institute workshop:
      October 2-4, 2002: executive summary.

PMID- 14970121
TI  - Cardiology patient page. Mitral valve disease.

PMID- 14970122
TI  - Images in cardiovascular medicine. Pseudoaneurysms of the ascending aorta
      demonstrated with "motion-free" multislice computed tomography.

PMID- 14970123
TI  - Women's Ischemic Syndrome Evaluation: current status and future research
      directions: report of the National Heart, Lung and Blood Institute workshop:
      October 2-4, 2002: Section 1: diagnosis of stable ischemia and ischemic heart
      disease.

PMID- 14970124
TI  - Women's Ischemic Syndrome Evaluation: current status and future research
      directions: report of the National Heart, Lung and Blood Institute workshop:
      October 2-4, 2002: Section 2: stable ischemia: pathophysiology and gender
      differences.

PMID- 14970125
TI  - Women's Ischemic Syndrome Evaluation: current status and future research
      directions: report of the National Heart, Lung and Blood Institute workshop:
      October 2-4, 2002: Section 3: diagnosis and treatment of acute cardiac ischemia:
      gender issues.

PMID- 14970126
TI  - Women's Ischemic Syndrome Evaluation: current status and future research
      directions: report of the National Heart, Lung and Blood Institute workshop:
      October 2-4, 2002 : Section 4: lessons from hormone replacement trials.

PMID- 14970127
TI  - Women's Ischemic Syndrome Evaluation: current status and future research
      directions: report of the National Heart, Lung and Blood Institute workshop:
      October 2-4, 2002: Section 5: gender-related risk factors for ischemic heart
      disease.

PMID- 14970128
TI  - Women's Ischemic Syndrome Evaluation: current status and future research
      directions: report of the National Heart, Lung and Blood Institute workshop:
      October 2-4, 2002: Section 6: key messages about acute ischemic heart disease in
      women and recommendations for practice.

PMID- 14970129
TI  - Women's Ischemic Syndrome Evaluation: current status and future research
      directions: report of the National Heart, Lung and Blood Institute workshop:
      October 2-4, 2002: perspective: new frontiers in detection of ischemic heart
      disease in women.

PMID- 14970131
TI  - 'It ain't what you do; it's the way that you do it.': reducing haemodynamic
      instability during carotid surgery.

PMID- 14970132
TI  - Anaesthesia for off-pump coronary artery surgery.

PMID- 14970133
TI  - Opioids for persistent non-cancer pain: recommendations for clinical practice.

PMID- 14970134
TI  - Remifentanil by bolus injection: a safety, pharmacokinetic, pharmacodynamic, and
      age effect investigation in human volunteers.
AB  - BACKGROUND: Although remifentanil's short-acting pharmacokinetic profile makes it
      well suited for procedures during which a brief period of intense analgesia is
      required, setting up an infusion pump for brief procedures is inconvenient. The
      clinical pharmacology of remifentanil administered by bolus injection, a more
      convenient alternative, has not been explored in detail. The primary aim of this
      study was to examine the safety of single bolus doses of remifentanil in
      conscious, healthy, adult volunteers breathing room air. Secondary aims included
      the evaluation of remifentanil pharmacokinetics and analgesic effects after bolus
      injection and a comparison of these issues in younger vs older adults. METHODS:
      Using a randomized, double-blind, placebo-controlled, dose-escalation, crossover
      study design, 64 subjects (16 over 60 years old) received remifentanil or placebo
      by bolus injection in a fixed unit dose separated by a 1 h washout period.
      Respiratory effects were assessed using a respiratory intervention scale.
      Analgesic effects were assessed using pressure algometry. A population
      pharmacokinetic model was constructed using non-linear, mixed-effects modelling
      techniques based on arterial blood samples. Computer simulations were performed
      to illustrate the clinical application of the pharmacokinetic model. RESULTS:
      Dose-related increases in both respiratory and analgesic effects were observed.
      In general, the respiratory depression observed was mild and easily treated with
      requests to breathe or the administration of oxygen, although the older cohort
      (and some younger subjects) experienced more substantial respiratory depression
      at lower doses. The pharmacokinetics of bolus-dose remifentanil were adequately
      described by a two-compartment model. The pharmacokinetic simulations illustrated
      the potential utility of bolus-dose remifentanil. CONCLUSIONS: Bolus injection
      could potentially be a safe and effective means of administering remifentanil in
      clinical situations requiring a brief period of intense analgesia. Because some
      subjects, both old and young, experienced significant respiratory depression even
      at low doses, careful monitoring of respiratory function is essential.

PMID- 14970135
TI  - Alkalinization of intra-cuff lidocaine and use of gel lubrication protect against
      tracheal tube-induced emergence phenomena.
AB  - BACKGROUND: We sought to determine the benefits of using alkalinized lidocaine 40
      mg to fill the cuff of a tracheal tube (ETT) in combination with water-soluble
      gel lubrication to prevent post-intubation sore throat. METHODS: The work
      included an in vitro study of the diffusion of alkalinized lidocaine solution
      through the low-pressure, high-volume cuff of an ETT. We also performed a
      randomized controlled study (n=20 patients in each group) that included a group
      who received an alkalinized lidocaine-filled ETT cuff with lubrication of the
      tube using water-soluble gel (Group G), and two control groups who received an
      alkalinized lidocaine-filled cuff with ETT lubrication with water (Group W) or an
      air-filled cuff with ETT lubrication with water (Group C). RESULTS: Water-soluble
      gel lubrication (Group G) produced a lower incidence of sore throat during the 24
      h post-extubation period than lubrication with water alone in the cuffs filled
      with alkalinized lidocaine (Group W), and compared with the air control group.
      The ability of lidocaine to pass through the cuff of an ETT when water-soluble
      gel and/or water alone was used as a lubricant was similar, as determined by
      lidocaine plasma concentrations (C(max) 45 ng x ml(-1)). Cough and restlessness
      before tracheal extubation were decreased in patients with the alkalinized
      lidocaine-filled cuffs compared with the air-filled cuffs. After extubation,
      nausea, vomiting, dysphonia and hoarseness were greater for patients with air
      filled cuffs compared with the lidocaine-filled cuffs. No significant difference
      between the groups was recorded in arterial blood pressure and heart rate. In
      vitro data suggest that the lower the NaHCO(3) injection volume, the greater the
      release of lidocaine across a low-pressure, high-volume cuff. CONCLUSIONS: These
      data show benefits of using an alkalinized lidocaine-filled ETT cuff in
      combination with water-soluble gel lubrication in preventing post-intubation sore
      throat.

PMID- 14970136
TI  - Off-pump coronary artery bypass surgery: physiology and anaesthetic management.
AB  - Increasing interest is being shown in beating heart (off-pump) coronary artery
      surgery (OPCAB) because, compared with operations performed with cardiopulmonary
      bypass, OPCAB surgery may be associated with decreased postoperative morbidity
      and reduced total costs. Its appears to produce better results than conventional
      surgery in high-risk patient populations, elderly patients, and those with
      compromised cardiac function or coagulation disorders. Recent improvements in the
      technique have resulted in the possibility of multiple-vessel grafting in all
      coronary territories, with a graft patency comparable with conventional surgery.
      During beating-heart surgery, anaesthetists face two problems: first, the
      maintenance of haemodynamic stability during heart enucleation necessary for
      accessing each coronary artery; and second, the management of intraoperative
      myocardial ischaemia when coronary flow must be interrupted during grafting. The
      anaesthetic technique is less important than adequate management of these two
      major constraints. However, experimental and recent clinical data suggest that
      volatile anaesthetics have a marked cardioprotective effect against ischaemia,
      and might be specifically indicated. OPCAB surgery requires team work between
      anaesthetists and surgeons, who must be aware of each other's constraints. Some
      surgical aspects of the operation are reviewed along with physiological and
      anaesthetic data.

PMID- 14970137
TI  - Puerperal uterine inversion and shock.
AB  - Uterine inversion is an unusual and potentially life-threatening event occurring
      in the third stage of labour. It is associated with significant blood loss, and
      shock, which may be out of proportion to the haemorrhage, although this is
      questionable. When managed promptly and aggressively, uterine inversion can
      result in minimal maternal morbidity and mortality. A recent case is described,
      followed by a short review of the literature.

PMID- 14970138
TI  - Accreditation in transoesophageal echocardiography.

PMID- 14970139
TI  - Dose of intrathecal diamorphine for Caesarean section and position for spinal
      insertion.

PMID- 14970140
TI  - Post-dural puncture headache.

PMID- 14970141
TI  - Topical anaesthesia in neonates, infants and children.

PMID- 14970142
TI  - Anaesthesia and pseudoseizures.

PMID- 14970143
TI  - Desflurane might not be the optimal volatile anaesthetic in morbidly obese
      patients.

PMID- 14970144
TI  - Corticosteroids for supraglottitis.

PMID- 14970145
TI  - How low can we go?

PMID- 14970146
TI  - Cognitive impairment and decline are associated with carotid artery disease in
      patients without clinically evident cerebrovascular disease.
AB  - BACKGROUND: Whether carotid artery disease is a cause of cognitive impairment in
      persons who have not had stroke is unknown. If this is the case, diminished
      performance on the Modified Mini-Mental State Examination should be more common
      in persons with left carotid artery disease than in those with right carotid
      artery disease. OBJECTIVE: To determine whether left carotid artery disease is
      associated with cognitive impairment. DESIGN: Cross-sectional and cohort study.
      SETTING: Four U.S. communities participating in the Cardiovascular Health Study.
      PATIENTS: 4006 right-handed men and women 65 years of age or older without
      history of stroke, transient ischemic attack, or carotid endarterectomy.
      MEASUREMENTS: Internal carotid artery stenosis and intima-media thickness of the
      common carotid artery were assessed by using duplex ultrasonography. Cognitive
      impairment was defined as a score less than 80 on the Modified Mini-Mental State
      Examination, and cognitive decline was defined as an average decrease of more
      than 1 point annually in Modified Mini-Mental State Examination score during up
      to 5 years of follow-up. Multivariate logistic regression models were used to
      estimate the risk for cognitive impairment and decline associated with left
      internal carotid artery stenosis and intima-media thickness, after adjustment for
      measures of right-sided disease and risk factors for vascular disease. RESULTS:
      After adjustment for right-sided stenosis, high-grade (> or =75% narrowing of
      diameter) stenosis of the left internal carotid artery (32 patients) was
      associated with cognitive impairment (odds ratio, 6.7 [95% CI, 2.4 to 18.1]
      compared with no stenosis) and cognitive decline (odds ratio, 2.6 [CI, 1.1 to
      6.3]). Intima-media thickness of the left common carotid artery was associated
      with cognitive impairment and decline in univariate analysis, but this effect did
      not persist after adjustment. CONCLUSIONS: Cognitive impairment and decline are
      associated with asymptomatic high-grade stenosis of the left internal carotid
      artery. The persistence of the association after adjustment for right-sided
      stenosis indicates that the association is not due to underlying vascular risk
      factors or atherosclerosis in general.

PMID- 14970147
TI  - Retinal arteriolar diameter and risk for hypertension.
AB  - BACKGROUND: Narrowing of the small arterioles has been hypothesized to contribute
      to the pathogenesis of hypertension, but prospective clinical data are lacking.
      OBJECTIVE: To examine the relation of retinal arteriolar narrowing to incident
      hypertension in healthy middle-aged persons. DESIGN: Prospective cohort study.
      SETTING: The population-based Atherosclerosis Risk in Communities Study,
      conducted in 4 U.S. communities. PARTICIPANTS: 5628 persons 49 to 73 years of age
      without preexisting hypertension. MEASUREMENTS: Diameters of retinal vessels were
      measured from digitized retinal photographs. A summary arteriole-to-venule ratio
      was computed as an indicator of generalized arteriolar narrowing; a lower ratio
      indicated greater narrowing. Areas of focal arteriolar narrowing were defined
      from photographs by using a standard protocol. Incident hypertension, defined as
      systolic blood pressure of 140 mm Hg or higher, diastolic blood pressure of 90 mm
      Hg or higher, or use of antihypertensive medication, was identified from the
      cohort. RESULTS: After 3 years of follow-up, 811 (14.4%) persons had developed
      hypertension. The incidence of hypertension was higher in persons with lower
      arteriole-to-venule ratios (incidence of 8.9%, 12.3%, 13.7%, 14.3%, and 22.3%,
      comparing decreasing quintiles of the ratio) and in persons with focal arteriolar
      narrowing than in those without focal arteriolar narrowing (25.1% vs. 13.0%).
      After the authors controlled for the average systolic and diastolic blood
      pressures over the preceding 6 years, body mass index, waist-to-hip ratio, and
      other risk factors, the odds of developing hypertension were approximately 60%
      higher in persons with lower arteriole-to-venule ratios (odds ratio, 1.62 [95%
      CI, 1.21 to 2.18] comparing lowest to highest quintile; P = 0.006 for trend) and
      focal arteriolar narrowing (odds ratio, 1.61 [CI, 1.27 to 2.04]; P < 0.001).
      CONCLUSIONS: Smaller retinal arteriolar diameters are independently associated
      with incident hypertension, which suggests that arteriolar narrowing may be
      linked to the occurrence and development of hypertension.

PMID- 14970148
TI  - The prognostic importance of changes in CD4+ cell count and HIV-1 RNA level in
      women after initiating highly active antiretroviral therapy.
AB  - BACKGROUND: The prognostic value of CD4+ cell counts and HIV-1 RNA levels
      attained after the initiation of highly active antiretroviral therapy (HAART)
      compared with before the initiation of HAART has not been well defined.
      OBJECTIVE: To determine the prognostic value for clinical outcomes of CD4+ cell
      counts and HIV-1 RNA levels attained after initiating therapy. DESIGN:
      Prospective cohort study. SETTING: Women's Interagency HIV Study. PATIENTS: 1132
      participants in the Women's Interagency HIV Study. MEASUREMENTS: HIV-1 RNA level,
      CD+ cell counts, AIDS-defining illness, and death. RESULTS: In multivariate
      analyses with a median follow-up of 3.9 years, women with CD4+ cell counts of
      less than 0.200 x 10(9) cells/L compared with women with CD4+ cell counts of
      greater than 0.350 x 10(9) cells/L after HAART initiation had a relative hazard
      of death from all causes of 2.66 (95% CI, 1.42 to 4.99) and a relative hazard of
      death from AIDS of 47.61 (CI, 5.69 to 398.40). The relative hazard of all-cause
      death was 3.44 (CI, 1.67 to 7.09) in women with RNA levels of more than 10 000
      copies/mL compared with women with attained RNA levels of less than 80 copies/mL.
      The relative hazard of AIDS-related or all-cause death did not increase for women
      with post-HAART CD4+ cell counts between 0.200 and 0.350 x 10(9) cells/L compared
      with women with CD4+ cell counts of greater than 0.350 x 10(9) cells/L. Also, the
      relative hazard did not increase in women with post-HAART HIV-1 RNA levels
      between 80 and 10 000 copies/mL compared with women with post-HAART HIV-1 RNA
      levels of less than 80 copies/mL. Of the laboratory markers, only the post-HAART
      CD4+ cell count and HIV-1 RNA level were predictive of new AIDS-defining illness.
      CONCLUSION: Post-HAART laboratory markers predicted death and new AIDS-defining
      illness. Pre-HAART CD4+ cell count and HIV-1 RNA level were not predictive of
      clinical outcomes if adjusted for values attained after HAART initiation,
      suggesting that even advanced immune suppression can be overcome with HAART that
      results in CD4+ cell counts of greater than 0.200 x 10(9) cells/L and RNA levels
      of less than 10 000 copies/mL.

PMID- 14970149
TI  - The natural history of lone atrial flutter.
AB  - BACKGROUND: The natural history of atrial flutter is not well defined. OBJECTIVE:
      To report the risk for stroke, conversion to atrial fibrillation, and
      anticoagulation for lone atrial flutter. DESIGN: Retrospective cohort analysis.
      SETTING: A clinically based longitudinal study of inpatients and outpatients with
      atrial flutter. PATIENTS: The authors compared the stroke rate in 59 patients
      with atrial flutter with rates in a sample in which age- and sex-specific
      ischemic cerebrovascular event rates were determined and in a sample of
      nonhypertensive patients with lone atrial fibrillation. The risk for developing
      atrial fibrillation after presenting with atrial flutter is also reported.
      MEASUREMENTS: Electrocardiograms and clinical data were collected and reviewed
      for each study participant. RESULTS: After adjustment for age and sex, patients
      with atrial flutter had a higher incidence of thromboembolic events than the
      sample control patients and patients with atrial fibrillation. Atrial
      fibrillation developed in 56% of patients with atrial flutter. CONCLUSIONS: Lone
      atrial flutter has a stroke risk at least as high as lone atrial fibrillation and
      carries a higher risk for subsequent development of atrial fibrillation than in
      the general population. Anticoagulation should be considered for all patients
      with atrial flutter who are older than 65 years of age.

PMID- 14970150
TI  - Medicare program expenditures associated with hospice use.
AB  - BACKGROUND: Hospice providers contend that enrollment reduces the cost of the
      Medicare programs, but estimates of effects are dated, methodologically limited,
      and focused on persons with cancer. OBJECTIVE: To estimate the effects of hospice
      care on Medicare program payments during the last year of life from 1996 to 1999
      within cohorts defined by age and diagnosis. DESIGN: Retrospective cohort.
      SETTING: Deceased Medicare enrollees. PARTICIPANTS: Elderly Medicare fee-for
      service beneficiaries who received 36 months of continuous Part A and B coverage
      before death during 1996 to 1999 (n = 245 326). Age- and condition-specific
      (cancer or noncancer and principal condition) cohorts were defined. MEASUREMENTS:
      Medicare expenditures in the last year of life, as a total figure and by service
      type. The cost effects of hospice were estimated by using linear regression
      within the cohorts for hospice enrollees compared with nonenrollees after
      adjustment for propensity to use hospice, gender, race, enrollment in Medicaid,
      urban setting, duration of illness, comorbid conditions, low use of Medicare,
      nursing home residence, and year of death. RESULTS: Adjusted mean expenditures
      were 4.0% higher overall among hospice enrollees than among nonenrollees.
      Adjusted mean expenditures were 1% lower for hospice enrollees with cancer than
      for patients with cancer who did not use hospice. Savings were highest (7% to
      17%) among enrollees with lung cancer and other very aggressive types of cancer
      diagnosed in the last year of life. Expenditures for hospice enrollees without
      cancer were 11% higher than for nonenrollees, ranging from 20% to 44% for
      patients with dementia and 0% to 16% for those with chronic heart failure or
      failure of most other organ systems. Hospice-related savings decreased and
      relative costs increased with age. CONCLUSION: Hospice enrollment correlates with
      reduced Medicare expenditures among younger decedents with cancer but increased
      expenditures among decedents without cancer and those older than 84 years of age.
      Future studies should assess the effects of hospice on quality and on
      expenditures from all payment sources.

PMID- 14970151
TI  - Evidence-based diagnostic strategies for evaluating suspected allergic rhinitis.
AB  - Allergic rhinitis is an increasingly common disease, with a prevalence of at
      least 10% to 25% in the United States. Diagnostic allergy tests, such as skin
      tests and in vitro tests, can assist clinicians in determining whether nasal
      symptoms are allergic in origin. In addition, safe and effective medications are
      available to treat allergic rhinitis. The initial strategy should be to determine
      whether patients should undergo diagnostic testing or receive empirical
      treatment. This paper reviews the test characteristics of the history, skin
      tests, and in vitro tests in diagnosing allergic rhinitis from the perspective of
      decision thresholds. A combination of pertinent medical history features in a
      practice with a high baseline prevalence of allergic rhinitis justifies the
      common practice of empirical treatment since allergy medication has minimal
      toxicity and side effects. The situation is more complex when the patient needs a
      diagnostic test, because reported sensitivities and specificities of skin tests
      and in vitro tests vary widely. As a result, it is difficult to calculate the
      post-test probability of allergic rhinitis with any confidence. The decision to
      initiate diagnostic testing must rely on clinical judgment to select patients who
      would benefit most from determining their allergic status while minimizing
      unnecessary testing and medications. Diagnosing allergy to a specific antigen
      allows patients to avoid the allergen and makes them candidates for allergen
      immunotherapy, which can decrease the need for medications.

PMID- 14970152
TI  - Update in infectious diseases.

PMID- 14970153
TI  - Medical device regulation: an introduction for the practicing physician.
AB  - Patient care for the practicing physician increasingly relies on medical devices.
      The U.S. Food and Drug Administration is responsible for the safety and
      effectiveness of medical devices in the United States. In addition to playing a
      role in the clinical use of devices, physicians may also participate in their
      design, production, use, and safety by expressing their need for certain
      products, by providing practical input and feedback into product design, by
      participating in device-related research, and by reporting device-related adverse
      events. Physicians should understand the rules that govern the approved and
      unapproved use of medical devices as well as device premarket evaluation and
      approval processes and device postmarket surveillance.

PMID- 14970154
TI  - Carotid disease and cognitive dysfunction.

PMID- 14970155
TI  - Starting highly active antiretroviral therapy for HIV infection: is it WIHS to
      wait?

PMID- 14970156
TI  - To be a doctor in Jerusalem: life under threat of terrorism.

PMID- 14970157
TI  - The symbol of modern medicine.

PMID- 14970158
TI  - The symbol of modern medicine.

PMID- 14970159
TI  - The symbol of modern medicine.

PMID- 14970160
TI  - The symbol of modern medicine.

PMID- 14970161
TI  - The symbol of modern medicine.

PMID- 14970162
TI  - The symbol of modern medicine.

PMID- 14970163
TI  - The symbol of modern medicine.

PMID- 14970164
TI  - The symbol of modern medicine.

PMID- 14970165
TI  - The symbol of modern medicine.

PMID- 14970166
TI  - High-dose and low-dose cosyntropin stimulation tests for diagnosis of adrenal
      insufficiency.

PMID- 14970167
TI  - Responsiveness of thrombotic thrombocytopenic purpura to rituximab and
      cyclophosphamide.

PMID- 14970168
TI  - The promise of disease proteomics: faster detection, diagnosis, and drug
      development.

PMID- 14970169
TI  - Summaries for patients. Cognitive function and carotid artery disease.

PMID- 14970170
TI  - Summaries for patients. Do narrowed blood vessels lead to hypertension?

PMID- 14970171
TI  - Summaries for patients. The relationship of pre- and post-treatment laboratory
      tests with outcomes for women starting treatment for HIV infection.

PMID- 14970172
TI  - Summaries for patients. Outcomes of patients with lone atrial flutter.

PMID- 14970173
TI  - Duration of antibiotic therapy for Lyme disease.

PMID- 14970174
TI  - Dark rounds.

PMID- 14970175
TI  - p38-MAPK signals survival by phosphorylation of caspase-8 and caspase-3 in human
      neutrophils.
AB  - Neutrophil apoptosis occurs both in the bloodstream and in the tissue and is
      considered essential for the resolution of an inflammatory process. Here, we show
      that p38-mitogen-activated protein kinase (MAPK) associates to caspase-8 and
      caspase-3 during neutrophil apoptosis and that p38-MAPK activity, previously
      shown to be a survival signal in these primary cells, correlates with the levels
      of caspase-8 and caspase-3 phosphorylation. In in vitro experiments,
      immunoprecipitated active p38-MAPK phosphorylated and inhibited the activity of
      the active p20 subunits of caspase-8 and caspase-3. Phosphopeptide mapping
      revealed that these phosphorylations occurred on serine-364 and serine-150,
      respectively. Introduction of mutated (S150A), but not wild-type, TAT-tagged
      caspase-3 into primary neutrophils made the Fas-induced apoptotic response
      insensitive to p38-MAPK inhibition. Consequently, p38-MAPK can directly
      phosphorylate and inhibit the activities of caspase-8 and caspase-3 and thereby
      hinder neutrophil apoptosis, and, in so doing, regulate the inflammatory
      response.

PMID- 14970176
TI  - Specific regulation of T helper cell 1-mediated murine colitis by CEACAM1.
AB  - Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) is a cell
      surface molecule that has been proposed to negatively regulate T cell function.
      We have shown that CEACAM1 is associated with specific regulation of T helper
      cell (Th)1 pathways, T-bet-mediated Th1 cytokine signaling, and Th1-mediated
      immunopathology in vivo. Mice treated with anti-mouse CEACAM1-specific monoclonal
      antibody (mAb) CC1 during the effector phase exhibited a reduced severity of
      trinitrobenzene sulfonic acid colitis in association with decreased interferon
      (IFN)-gamma production. Although oxazolone colitis has been reported as Th2
      mediated, mice treated with the CC1 mAb or a CEACAM1-Fc chimeric protein
      exhibited a reduced severity of colitis in association with a significant
      reduction of IFN-gamma and T-bet activation, whereas signal transducer and
      activator of antigen 4 activation was unaffected. Both interleukin-4 and IFN
      gamma gene-deficient mice exhibited less severe colitis induction by oxazolone.
      Direct ligation of T cells in vitro with the murine hepatitis virus spike
      protein, a natural ligand for the N-domain of CEACAM1, inhibited the
      differentiation of naive cells into Th1 but not Th2 cells and activation of Th1
      but not Th2 cytokine production. These results indicate that CEACAM1 isoforms are
      a novel class of activation-induced cell surface molecules on T cells that
      function in the specific regulation of Th1-mediated inflammation such as that
      associated with inflammatory bowel disease.

PMID- 14970177
TI  - N-linked glycosylation is required for optimal function of Kaposi's sarcoma
      herpesvirus-encoded, but not cellular, interleukin 6.
AB  - Kaposi's sarcoma-associated herpesvirus interleukin-6 (vIL-6) is a structural and
      functional homologue of the human cytokine IL-6 (hIL-6). hIL-6 and vIL-6 exhibit
      similar biological functions and both act via the gp130 receptor subunit to
      activate the Janus tyrosine kinase (JAK)1 and signal transducer and activator of
      transcription (STAT)1/3 pathway. Here we show that vIL-6 is N-linked glycosylated
      at N78 and N89 and demonstrate that N-linked glycosylation at site N89 of vIL-6
      markedly enhances binding to gp130, signaling through the JAK1-STAT1/3 pathway
      and functions in a cytokine-dependent cell proliferation bioassay. Although hIL-6
      is also N-glycosylated at N73 and multiply O-glycosylated, neither N-linked nor O
      linked glycosylation is necessary for IL-6 receptor alpha-dependent binding to
      gp130 or signaling through JAK1-STAT1/3. As distinct from vIL-6, unglycosylated
      hIL-6 is as potent as glycosylated hIL-6 in stimulating B cell proliferation.
      These findings highlight distinct functional roles of N-linked glycosylation in
      viral and cellular IL-6.

PMID- 14970178
TI  - Exogenous pathogen and plant 15-lipoxygenase initiate endogenous lipoxin A4
      biosynthesis.
AB  - Lipoxin A4 (LXA4) is a potent endogenous lipoxygenase-derived eicosanoid with
      antiinflammatory and proresolving properties. Supraphysiological levels of LXA4
      are generated during infection by Toxoplasma gondii, which in turn reduces
      interleukin (IL) 12 production by dendritic cells, thus dampening Th1-type cell
      mediated immune responses and host immunopathology. In the present work, we
      sought evidence for the structural basis of T. gondii's ability to activate LXA4
      biosynthesis. Proteomic analysis of T. gondii extract (soluble tachyzoite antigen
      [STAg]), which preserves the immunosuppressive and antiinflammatory activity of
      the parasite, yielded several peptide matches to known plant lipoxygenases.
      Hence, we incubated STAg itself with arachidonic acid and found using LC-UV-MS-MS
      based lipidomics that STAg produced both 15-HETE and 5,15-diHETE, indicating that
      T. gondii carries 15-lipoxygenase activity. In addition, T. gondii tachyzoites
      (the rapidly multiplying and invasive stage of the parasite) generated LXA4 when
      provided with arachidonic acid. Local administration of a plant (soybean)
      lipoxygenase itself reduced neutrophilic infiltration in murine peritonitis,
      demonstrating that 15-lipoxygenase possesses antiinflammatory properties.
      Administration of plant 15-lipoxygenase generated endogenous LXA4 and mimicked
      the suppression of IL-12 production by splenic dendritic cells observed after T.
      gondii infection or STAg administration. Together, these results indicate that 15
      lipoxygenase expressed by a pathogen as well as exogenously administered 15
      lipoxygenase can interact with host biosynthetic circuits for endogenous "stop
      signals" that divert the host immune response and limit acute inflammation.

PMID- 14970179
TI  - Activation of natural killer cells and dendritic cells upon recognition of a
      novel CD99-like ligand by paired immunoglobulin-like type 2 receptor.
AB  - Paired receptors that consist of highly related activating and inhibitory
      receptors are widely involved in the regulation of the immune system. Here, we
      report a mouse orthologue of the human activating paired immunoglobulin-like type
      2 receptor (PILR) beta, which was cloned from a cDNA library of natural killer
      (NK) cells based on its ability to associate with the DAP12 signaling adaptor
      protein. The activating PILRbeta was expressed not only on NK cells but also on
      dendritic cells and macrophages. Furthermore, we have identified a novel CD99
      like molecule as a ligand for the activating PILRbeta and inhibitory PILRalpha
      receptors. Transcripts of PILR ligand are present in many tissues, including some
      T cell lines. Cells expressing the PILR ligand specifically activated NK cells
      and dendritic cells that express the activating PILRbeta. Our findings reveal a
      new regulatory mechanism of innate immunity by PILR and its CD99-like ligand.

PMID- 14970180
TI  - Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation
      and hyperresponsiveness in a naive host mouse.
AB  - Interleukin (IL)-18 was originally regarded to induce T helper cell (Th)1-related
      cytokines. In general, factors favoring interferon (IFN)-gamma production are
      believed to abolish allergic diseases. Thus, we tested the role of IL-18 in
      regulation of bronchial asthma. To avoid a background response of host-derived T
      cells, we administered memory type Th1 or Th2 cells into unsensitized mice and
      examined their role in induction of bronchial asthma. Administration of antigen
      (Ag) induced both airway inflammation and airway hyperresponsiveness (AHR) in
      mice receiving memory Th2 cells. In contrast, the same treatment induced only
      airway inflammation but not AHR in mice receiving memory Th1 cells. However,
      these mice developed striking AHR when they were coadministered with IL-18.
      Furthermore, mice having received IFN-gamma-expressing Th1 cells sorted from
      polarized Th1 cells developed severe airway inflammation and AHR after intranasal
      administration of Ag and IL-18. Thus, Th1 cells become harmful when they are
      stimulated with Ag and IL-18. Newly polarized Th1 cells and IFN-gamma-expressing
      Th1 cells, both of which express IL-18 receptor alpha chain strongly, produce IFN
      gamma, IL-9, IL-13, granulocyte/macrophage colony-stimulating factor, tumor
      necrosis factor alpha, regulated on activation, normal T cell expressed and
      secreted, and macrophage inflammatory protein 1alpha upon stimulation with Ag, IL
      2, and IL-18 in vitro. Thus, Ag and IL-18 stimulate memory Th1 cells to induce
      severe airway inflammation and AHR in the naive host.

PMID- 14970181
TI  - Deficiency of the cyclin kinase inhibitor p21(WAF-1/CIP-1) promotes apoptosis of
      activated/memory T cells and inhibits spontaneous systemic autoimmunity.
AB  - A characteristic feature of systemic lupus erythematosus is the accumulation of
      activated/memory T and B cells. These G0/G1-arrested cells express high levels of
      cyclin-dependent kinase inhibitors such as p21, are resistant to proliferation
      and apoptosis, and produce large amounts of proinflammatory cytokines. Herein, we
      show that ablation of p21 in lupus-prone mice allows these cells to reenter the
      cell cycle and undergo apoptosis, leading to autoimmune disease reduction.
      Absence of p21 resulted in enhanced Fas/FasL-mediated activation-induced T cell
      death, increased activation of procaspases 8 and 3, and loss of mitochondrial
      transmembrane potential. Increased apoptosis was also associated with p53 up
      regulation and a modest shift in the ratio of Bax/Bcl-2 toward the proapoptotic
      Bax. Proliferation and apoptosis of B cells were also increased in p21-/- lupus
      mice. Thus, modulation of the cell cycle pathway may be a novel approach to
      reduce apoptosis-resistant pathogenic lymphocytes and to ameliorate systemic
      autoimmunity.

PMID- 14970182
TI  - CpG-matured murine plasmacytoid dendritic cells are capable of in vivo priming of
      functional CD8 T cell responses to endogenous but not exogenous antigens.
AB  - Plasmacytoid dendritic cells (PDCs) are a unique leukocyte population capable of
      secreting high levels of type I interferon (IFN) in response to viruses and
      bacterial stimuli. In vitro experiments have shown that upon maturation, human
      and murine PDCs develop into potent immunostimulatory cells; however, their
      ability to prime an immune response in vivo remains to be addressed. We report
      that CpG-matured murine PDCs are capable of eliciting in naive mice antigen
      specific CTLs against endogenous antigens as well as exogenous peptides, but not
      against an exogenous antigen. Type I IFN is not required for priming, as
      injection of CpG-matured PDCs into type I IFN receptor-deficient mice elicits
      functional CTL responses. Mature PDCs prime CTLs that secrete IFN-gamma and
      protect mice from a tumor challenge. In contrast, immature PDCs are unable to
      prime antigen-specific CTLs. However, mice injected with immature PDCs are fully
      responsive to secondary antigenic challenges, suggesting that PDCs have not
      induced long-lasting tolerance via anergic or regulatory T cells. Our results
      underline the heterogeneity and plasticity of different antigen-presenting cells,
      and reveal an important role of mature PDCs in priming CD8 responses to
      endogenous antigens, in addition to their previously reported ability to modulate
      antiviral responses via type I IFN.

PMID- 14970183
TI  - Identification of a cytokine-induced antiapoptotic molecule anamorsin essential
      for definitive hematopoiesis.
AB  - Many growth factors and cytokines prevent apoptosis. Using an expression cloning
      method, we identified a novel antiapoptotic molecule named Anamorsin, which does
      not show any homology to known apoptosis regulatory molecules such as Bcl-2
      family, caspase family, or signal transduction molecules. The expression of
      Anamorsin was completely dependent on stimulation with growth factors such as
      interleukin 3, stem cell factor, and thrombopoietin in factor-dependent
      hematopoietic cell lines, and forced expression of Anamorsin conferred resistance
      to apoptosis caused by growth factor deprivation in vitro. Furthermore, Anamorsin
      was found to act as an antiapoptotic molecule in vivo because Anamorsin-/- mice
      die in late gestation due to defective definitive hematopoiesis in the fetal
      liver (FL). Although the number of hematopoietic stem/progenitor cells in the FL
      did not decrease in these mice, myeloid, and particularly erythroid colony
      formation in response to cytokines, was severely disrupted. Also, Anamorsin-/-
      erythroid cells initiated apoptosis during terminal maturation. As for the
      mechanism of Anamorsin-mediated cell survival, a microarray analysis revealed
      that the expression of Bcl-xL and Jak2 was severely impaired in the FL of
      Anamorsin-/- mice. Thus, Anamorsin is considered to be a necessary molecule for
      hematopoiesis that mediates antiapoptotic effects of various cytokines.

PMID- 14970184
TI  - Combining gene expression profiles and clinical parameters for risk
      stratification in medulloblastomas.
AB  - PURPOSE: Stratification of risk in patients with medulloblastoma remains a
      challenge. As clinical parameters have been proven insufficient for accurately
      defining disease risk, molecular markers have become the focus of interest.
      Outcome predictions on the basis of microarray gene expression profiles have been
      the most accurate to date. We ask in a multivariate model whether clinical
      parameters enhance survival predictions of gene expression profiles. PATIENTS AND
      METHODS: In a cohort of 55 young patients (whose medulloblastoma samples have
      been analyzed previously for gene expression profile), associations between
      clinical and gene expression variables and survival were assessed using Cox
      proportional hazards models. Available clinical variables included age, stage
      (ie, the presence of disseminated disease at diagnosis), sex, histologic subtype,
      treatment, and status. RESULTS: Univariate analysis demonstrated expression
      profiles to be the only significant clinical prognostic factor (P=.03). In
      multivariate analysis, gene expression profiles predicted outcome independent of
      other criteria. Clinical criteria did not significantly contribute additional
      information for outcome predictions, although an exploratory analysis noted a
      trend for decreased survival of patients with metastases at diagnosis but
      favorable gene expression profile. CONCLUSION: Gene expression profiling predicts
      medulloblastoma outcome independent of clinical variables. These results need to
      be validated in a larger prospective study.

PMID- 14970185
TI  - Clinical, histopathologic, and molecular markers of prognosis: toward a new
      disease risk stratification system for medulloblastoma.
AB  - PURPOSE: To assess the feasibility of performing central molecular analyses of
      fresh medulloblastomas obtained from multiple institutions and using these data
      to identify prognostic markers for contemporaneously treated patients. MATERIALS
      AND METHODS: Ninety-seven samples of medulloblastoma were collected. Tumor
      content in samples was judged by frozen section review. Tumor ERBB2 protein and
      MYCC, MYCN, and TRKC mRNA levels were measured blind to clinical details using
      Western blotting and real-time polymerase chain reaction, respectively.
      Histopathologic and clinical review of each case was also performed. All data
      were subjected to independent statistical analysis. RESULTS: Sample acquisition
      and analysis times ranged from 3 to 6 days. Eighty-six samples contained
      sufficient tumor for analysis, including 38 classic, 30 nodular desmoplastic, and
      18 large-cell anaplastic (LCA) medulloblastomas. Protein and mRNA were extracted
      from 81 and 49 tumors, respectively. ERBB2 was detected in 40% (n=32 of 81) of
      tumors, most frequently in LCA disease (P=.005), and was independently associated
      with a poor prognosis (P=.031). A combination of clinical characteristics and
      ERBB2 expression provided a highly accurate means of discriminating disease risk.
      One hundred percent (n=26) of children with clinical average-risk, ERBB2-negative
      disease were alive at 5 years, with a median follow-up of 5.6 years, compared
      with only 54% for children with average-risk, ERBB2-positive tumors (n=13;
      P=.0001). TRKC, MYCC, and MYCN expression and histopathologic subtype were not
      associated with prognosis in this study. CONCLUSION: Central and rapid molecular
      analysis of frozen medulloblastomas collected from multiple institutions is
      feasible. ERBB2 expression and clinical risk factors together constitute a highly
      accurate disease risk stratification tool.

PMID- 14970186
TI  - Acute monocytic leukemia (French-American-British classification M5) does not
      have a worse prognosis than other subtypes of acute myeloid leukemia: a report
      from the Eastern Cooperative Oncology Group.
AB  - PURPOSE: Acute monocytic leukemia is a distinct subtype of acute myeloid leukemia
      (AML) with characteristic biologic and clinical features. This study was designed
      to compare the outcome of patients with M5 to that of other subtypes of AML, and
      to identify differences in M5a and M5b. PATIENTS AND METHODS: We reviewed all
      patients with AML M5 entered in three clinical trials for newly diagnosed AML
      conducted by the Eastern Cooperative Oncology Group between 1989 and 1998. Eighty
      one patients, 21 with M5a and 60 with M5b, were identified. RESULTS: The complete
      remission rate was 62% for all patients with M5; 52% for patients with M5a and
      65% for patients with M5b (P =.3), and 60% for the 1122 patients with non-M5 AML
      entered on the same clinical trials (P =.8 for M5 v non-M5). The 3-year disease
      free survival was 26% for all M5 patients; 18% for M5a and 28% for M5b (P =.31),
      and 33% for non-M5 patients (P =.13 for M5 v non-M5). The 3-year overall survival
      was 31% for all M5 patients; 33% for M5a and 30% for M5b (P =.65), and 30% for
      non-M5 (P =.74 for M5 v non-M5). The karyotypes of patients with AML M5 were
      heterogeneous. CD11b was the only leukemic cell antigen expressed differently in
      M5a (53%) compared to M5b (77%) to a significant degree (P =.02). CONCLUSION: AML
      M5 represents an immunologically heterogeneous population similar to non-M5 AML
      with a prognosis that is not dependent on morphology. The disease-free survival
      and overall survival of patients with M5a, M5b, and non-M5 appear not to differ
      with currently available therapy.

PMID- 14970187
TI  - Biologic risk stratification of medulloblastoma: the real time is now.

PMID- 14970188
TI  - Greatwall kinase: a nuclear protein required for proper chromosome condensation
      and mitotic progression in Drosophila.
AB  - Mutations in the Drosophila gene greatwall cause improper chromosome condensation
      and delay cell cycle progression in larval neuroblasts. Chromosomes are highly
      undercondensed, particularly in the euchromatin, but nevertheless contain
      phosphorylated histone H3, condensin, and topoisomerase II. Cells take much
      longer to transit the period of chromosome condensation from late G2 through
      nuclear envelope breakdown. Mutant cells are also subsequently delayed at
      metaphase, due to spindle checkpoint activity. These mutant phenotypes are not
      caused by spindle aberrations, by global defects in chromosome replication, or by
      activation of a caffeine-sensitive checkpoint. The Greatwall proteins in insects
      and vertebrates are located in the nucleus and belong to the AGC family of
      serine/threonine protein kinases; the kinase domain of Greatwall is interrupted
      by a long stretch of unrelated amino acids.

PMID- 14970189
TI  - Chronological aging leads to apoptosis in yeast.
AB  - During the past years, yeast has been successfully established as a model to
      study mechanisms of apoptotic regulation. However, the beneficial effects of such
      a cell suicide program for a unicellular organism remained obscure. Here, we
      demonstrate that chronologically aged yeast cultures die exhibiting typical
      markers of apoptosis, accumulate oxygen radicals, and show caspase activation.
      Age-induced cell death is strongly delayed by overexpressing YAP1, a key
      transcriptional regulator in oxygen stress response. Disruption of apoptosis
      through deletion of yeast caspase YCA1 initially results in better survival of
      aged cultures. However, surviving cells lose the ability of regrowth, indicating
      that predamaged cells accumulate in the absence of apoptotic cell removal.
      Moreover, wild-type cells outlast yca1 disruptants in direct competition assays
      during long-term aging. We suggest that apoptosis in yeast confers a selective
      advantage for this unicellular organism, and demonstrate that old yeast cells
      release substances into the medium that stimulate survival of the clone.

PMID- 14970190
TI  - Amylin inhibits bone resorption while the calcitonin receptor controls bone
      formation in vivo.
AB  - Amylin is a member of the calcitonin family of hormones cosecreted with insulin
      by pancreatic beta cells. Cell culture assays suggest that amylin could affect
      bone formation and bone resorption, this latter function after its binding to the
      calcitonin receptor (CALCR). Here we show that Amylin inactivation leads to a low
      bone mass due to an increase in bone resorption, whereas bone formation is
      unaffected. In vitro, amylin inhibits fusion of mononucleated osteoclast
      precursors into multinucleated osteoclasts in an ERK1/2-dependent manner.
      Although Amylin +/- mice like Amylin-deficient mice display a low bone mass
      phenotype and increased bone resorption, Calcr +/- mice display a high bone mass
      due to an increase in bone formation. Moreover, compound heterozygote mice for
      Calcr and Amylin inactivation displayed bone abnormalities observed in both Calcr
      +/- and Amylin +/- mice, thereby ruling out that amylin uses CALCR to inhibit
      osteoclastogenesis in vivo. Thus, amylin is a physiological regulator of bone
      resorption that acts through an unidentified receptor.

PMID- 14970191
TI  - Promyelocytic leukemia nuclear bodies associate with transcriptionally active
      genomic regions.
AB  - The promyelocytic leukemia (PML) protein is aggregated into nuclear bodies that
      are associated with diverse nuclear processes. Here, we report that the distance
      between a locus and its nearest PML body correlates with the transcriptional
      activity and gene density around the locus. Genes on the active X chromosome are
      more significantly associated with PML bodies than their silenced homologues on
      the inactive X chromosome. We also found that a histone-encoding gene cluster,
      which is transcribed only in S-phase, is more strongly associated with PML bodies
      in S-phase than in G0/G1 phase of the cell cycle. However, visualization of
      specific RNA transcripts for several genes showed that PML bodies were not
      themselves sites of transcription for these genes. Furthermore, knock-down of PML
      bodies by RNA interference did not preferentially change the expression of genes
      closely associated with PML bodies. We propose that PML bodies form in nuclear
      compartments of high transcriptional activity, but they do not directly regulate
      transcription of genes in these compartments.

PMID- 14970192
TI  - Mutagenesis of the putative sterol-sensing domain of yeast Niemann Pick C-related
      protein reveals a primordial role in subcellular sphingolipid distribution.
AB  - Lipid movement between organelles is a critical component of eukaryotic membrane
      homeostasis. Niemann Pick type C (NP-C) disease is a fatal neurodegenerative
      disorder typified by lysosomal accumulation of cholesterol and sphingolipids.
      Expression of yeast NP-C-related gene 1 (NCR1), the orthologue of the human NP-C
      gene 1 (NPC1) defective in the disease, in Chinese hamster ovary NPC1 mutant
      cells suppressed lipid accumulation. Deletion of NCR1, encoding a transmembrane
      glycoprotein predominantly residing in the vacuole of normal yeast, gave no
      phenotype. However, a dominant mutation in the putative sterol-sensing domain of
      Ncr1p conferred temperature and polyene antibiotic sensitivity without changes in
      sterol metabolism. Instead, the mutant cells were resistant to inhibitors of
      sphingolipid biosynthesis and super sensitive to sphingosine and C2-ceramide.
      Moreover, plasma membrane sphingolipids accumulated and redistributed to the
      vacuole and other subcellular membranes of the mutant cells. We propose that the
      primordial function of these proteins is to recycle sphingolipids and that
      defects in this process in higher eukaryotes secondarily result in cholesterol
      accumulation.

PMID- 14970193
TI  - Nudel functions in membrane traffic mainly through association with Lis1 and
      cytoplasmic dynein.
AB  - Nudel and Lis1 appear to regulate cytoplasmic dynein in neuronal migration and
      mitosis through direct interactions. However, whether or not they regulate other
      functions of dynein remains elusive. Herein, overexpression of a Nudel mutant
      defective in association with either Lis1 or dynein heavy chain is shown to cause
      dispersions of membranous organelles whose trafficking depends on dynein. In
      contrast, the wild-type Nudel and the double mutant that binds to neither protein
      are much less effective. Time-lapse microscopy for lysosomes reveals significant
      reduction in both frequencies and velocities of their minus end-directed motions
      in cells expressing the dynein-binding defective mutant, whereas neither the
      durations of movement nor the plus end-directed motility is considerably altered.
      Moreover, silencing Nudel expression by RNA interference results in Golgi
      apparatus fragmentation and cell death. Together, it is concluded that Nudel is
      critical for dynein motor activity in membrane transport and possibly other
      cellular activities through interactions with both Lis1 and dynein heavy chain.

PMID- 14970194
TI  - Phosphorylation of paxillin by p38MAPK is involved in the neurite extension of PC
      12 cells.
AB  - Cell adhesions play an important role in neurite extension. Paxillin, a focal
      adhesion adaptor protein involved in focal adhesion dynamics, has been
      demonstrated to be required for neurite outgrowth. However, the molecular
      mechanism by which paxillin regulates neurite outgrowth is unknown. Here, we show
      that paxillin is phosphorylated by p38MAPK in vitro and in nerve growth factor
      (NGF)-induced PC-12 cells. Ser 85 (Ser 83 for endogenous paxillin) is identified
      as one of major phosphorylation sites by phosphopeptide mapping and mass
      spectrometry. Moreover, expression of the Ser 85 --> Ala mutant of paxillin
      (paxS85A) significantly inhibits NGF-induced neurite extension of PC-12 cells,
      whereas expression of wild-type (wt) paxillin does not influence neurite
      outgrowth. Further experiments indicate that cells expressing paxS85A exhibit
      small, clustered focal adhesions which are not normally seen in cells expressing
      wt paxillin. Although wt paxillin and paxS85A have the same ability to bind
      vinculin and focal adhesion kinase, wt paxillin more efficiently associates with
      Pyk2 than paxS85A. Thus, phosphorylation of paxillin is involved in NGF-induced
      neurite extension of PC-12 cells, probably through regulating focal adhesion
      organization.

PMID- 14970195
TI  - A family of acid-sensing ion channels from the zebrafish: widespread expression
      in the central nervous system suggests a conserved role in neuronal
      communication.
AB  - Acid-sensing ion channels (ASICs) are excitatory receptors for extracellular
      H(+). Proposed functions include synaptic transmission, peripheral perception of
      pain, and mechanosensation. Despite the physiological importance of these
      functions, the precise role of ASICs has not yet been established. In order to
      increase our understanding of the physiological role and basic structure-function
      relationships of ASICs, we report here the cloning of six new ASICs from the
      zebrafish (zASICs). zASICs possess the basic functional properties of mammalian
      ASICs: activation by extracellular H(+), Na(+) selectivity, and block by
      micromolar concentrations of amiloride. The zasic genes are broadly expressed in
      the central nervous system, whereas expression in the peripheral nervous system
      is scarce. This pattern suggests a predominant role for zASICs in neuronal
      communication. Our results suggest a conserved function for receptors of
      extracellular H(+) in the central nervous system of vertebrates.

PMID- 14970196
TI  - The early onset dystonia protein torsinA interacts with kinesin light chain 1.
AB  - Early onset dystonia is a movement disorder caused by loss of a glutamic acid
      residue (Glu(302/303)) in the carboxyl-terminal portion of the AAA+ protein,
      torsinA. We identified the light chain subunit (KLC1) of kinesin-I as an
      interacting partner for torsinA, with binding occurring between the
      tetratricopeptide repeat domain of KLC1 and the carboxyl-terminal region of
      torsinA. Coimmunoprecipitation analysis demonstrated that wild-type torsinA and
      kinesin-I form a complex in vivo. In cultured cortical neurons, both proteins co
      localized along processes with enrichment at growth cones. Wild-type torsinA
      expressed in CAD cells co-localized with endogenous KLC1 at the distal end of
      processes, whereas mutant torsinA remained confined to the cell body. Subcellular
      fractionation of adult rat brain revealed torsinA and KLC associated with
      cofractionating membranes, and both proteins were co-immunoprecipitated after
      cross-linking cytoplasmically oriented proteins on isolated rat brain membranes.
      These studies suggest that wild-type torsinA undergoes anterograde transport
      along microtubules mediated by kinesin and may act as a molecular chaperone
      regulating kinesin activity and/or cargo binding.

PMID- 14970197
TI  - Scavenger receptor BI plays a role in facilitating chylomicron metabolism.
AB  - The function of scavenger receptor class B type I (SR-BI) in mediating the
      selective uptake of high density lipoprotein (HDL) cholesterol esters is well
      established. However, the potential role of SR-BI in chylomicron and chylomicron
      remnant metabolism is largely unknown. In the present investigation, we report
      that the cell association of 160 nm-sized triglyceride-rich chylomicron-like
      emulsion particles to freshly isolated hepatocytes from SR-BI-deficient mice is
      greatly reduced (>70%), as compared with wild-type littermate mice. Competition
      experiments show that the association of emulsion particles with isolated
      hepatocytes is efficiently competed for (>70%) by the well established SR-BI
      ligands, HDL and oxidized low density lipoprotein (LDL), whereas LDL is
      ineffective. Upon injection into SR-BI-deficient mice the hepatic association of
      emulsion particles is markedly decreased ( approximately 80%) as compared with
      wild-type mice. The relevance of these findings for in vivo chylomicron (remnant)
      metabolism was further evaluated by studying the effect of SR-BI deficiency on
      the intragastric fat load-induced postprandial triglyceride response. The
      postprandial triglyceride response is 2-fold higher in SR-BI-deficient mice as
      compared with wild-type littermates (area-under-the-curve 39.6 +/- 1.2 versus
      21.1 +/- 3.6; p < 0.005), with a 4-fold increased accumulation of chylomicron
      (remnant)-associated triglycerides in plasma at 6 h after intragastric fat load.
      We conclude that SR-BI is important in facilitating chylomicron (remnant)
      metabolism and might function as an initial recognition site for chylomicron
      remnants whereby the subsequent internalization can be exerted by additional
      receptor systems like the LDL receptor and LDL receptor-related protein.

PMID- 14970198
TI  - Functional and molecular characterization of naturally occurring mutations in the
      oocyte-secreted factors bone morphogenetic protein-15 and growth and
      differentiation factor-9.
AB  - Bone morphogenetic protein-15 (BMP-15) and growth and differentiation factor-9
      (GDF-9) are oocyte-secreted factors that are critical local regulators of ovarian
      physiology. Recent studies have identified a number of mutations in these genes
      that cause increased fertility and infertility in heterozygous or homozygous ewes
      carrying the mutations, respectively. Interestingly, heterozygous ewes with a
      mutation in both BMP-15 and GDF-9 exhibit higher fertility than those having
      mutation in only one of the genes. Here, we have produced recombinant human BMP
      15 and GDF-9 that carry the mutations identified in those sheep, i.e. I31D and
      S99I in BMP-15 and S77F in GDF-9. We found that when individually expressed, both
      BMP-15 mutations had no effect on the processing, secretion, and dimerization of
      the mature proteins or on the biological activity of the molecules. However, when
      mutant BMP-15 was co-expressed with wild-type GDF-9, the secretion of BMP-15 and
      GDF-9 was significantly reduced, suggesting that the mechanisms by which the BMP
      15 mutations affect sheep fertility occurs at the level of protein secretion
      rather than dimerization and biological activity. Moreover, when mutant GDF-9 was
      co-expressed with mutant BMP-15, the secretion levels of both proteins were
      significantly lower than those of cells co-expressing wildtype GDF-9 and mutant
      BMP-15, suggesting a possible mechanism for the extreme fertility observed in the
      compound heterozygous mutant sheep.

PMID- 14970199
TI  - Megakaryoblastic leukemia factor-1 transduces cytoskeletal signals and induces
      smooth muscle cell differentiation from undifferentiated embryonic stem cells.
AB  - The SAP domain transcription factor myocardin plays a critical role in the
      transcriptional program regulating smooth muscle cell differentiation. In this
      report, we describe the capacity of myocardin to physically associate with
      megakaryoblastic leukemia factor-1 (MKL1) and characterize the function of MKL1
      in smooth muscle cells (SMCs). The MKL1 gene is expressed in most human tissues
      and myocardin and MKL are co-expressed in SMCs. MKL1 and myocardin physically
      associate via conserved leucine zipper domains. Overexpression of MKL1
      transactivates serum response factor (SRF)-dependent SMC-restricted
      transcriptional regulatory elements including the SM22alpha promoter, smooth
      muscle myosin heavy chain promoter/enhancer, and SM-alpha-actin promoter/enhancer
      in non-SMCs. Moreover, forced expression of MKL1 and SRF in undifferentiated SRF(
      /-) embryonic stem cells activates multiple endogenous SMC-restricted genes at
      levels equivalent to, or exceeding, myocardin. Forced expression of a dominant
      negative MKL1 mutant reduces myocardin-induced activation of the SMC-specific
      SM22alpha promoter. In NIH3T3 fibroblasts MKL1 localizes to the cytoplasm and
      translocates to the nucleus in response to serum stimulation, actin treadmilling,
      and RhoA signaling. In contrast, in SMCs MKL1 is observed exclusively in the
      nucleus regardless of serum conditions or RhoA signaling. However, when actin
      polymerization is disrupted MKL1 translocates from the nucleus to the cytoplasm
      in SMCs. Together, these data were consistent with a model wherein MKL1
      transduces signals from the cytoskeleton to the nucleus in SMCs and regulates SRF
      dependent SMC differentiation autonomously or in concert with myocardin.

PMID- 14970200
TI  - Regulation of hepatic apolipoprotein B-lipoprotein assembly and secretion by the
      availability of fatty acids. I. Differential response to the delivery of fatty
      acids via albumin or remnant-like emulsion particles.
AB  - The in vivo effects of increased delivery of fatty acids (FA) to the liver are
      poorly defined. Therefore, we compared the effects of infusing either 6 mM oleic
      acid (OA) bound to albumin, 0.5-20% Intralipid, or saline for 3 or 6 h into male
      C57BL/6J mice. Infusions were followed by studies of triglyceride (TG) and apoB
      secretion. Although plasma FA levels increased similarly after either 20%
      Intralipid or 6 mM OA, TG secretion increased only after infusion of 4-20%
      Intralipid; TG secretion was unchanged by 6 mM OA. By contrast, 6-h infusions of
      either 6 mM OA or 4-20% Intralipid increased apoB secretion. 6 mM OA and 20%
      Intralipid each increased secretion of apoB from primary hepatocytes ex vivo.
      Importantly, 0.5-2% Intralipid, which delivered more FA to the liver than 6 mM
      OA, did not stimulate apoB secretion. Hepatic apoB mRNA levels were unaffected by
      either 6 mM OA or 20% Intralipid, but microsomal triglyceride transfer protein
      mRNA was significantly lower after 6-h infusions with 6 mM OA versus either
      saline or 20% Intralipid. Lower microsomal triglyceride transfer protein mRNA
      levels were associated with reduced hepatic TG mass after 6-h infusions of 6 mM
      OA. We conclude that 1) increased FA delivery to the liver in vivo increases
      secretion of apoB-lipoproteins via post-transcriptional mechanisms, 2) OA-induced
      apoB-lipoprotein secretion occurred at least in part via mechanisms other than by
      providing substrate for TG synthesis, and 3) the route of delivery of FA is
      important for its effects on apoB secretion.

PMID- 14970201
TI  - p21-activated kinase 1 phosphorylates and regulates 14-3-3 binding to GEF-H1, a
      microtubule-localized Rho exchange factor.
AB  - GEF-H1 is a guanine nucleotide exchange factor for Rho whose activity is
      regulated through a cycle of microtubule binding and release. Here we identify a
      region in the carboxyl terminus of GEF-H1 that is important for suppression of
      its guanine nucleotide exchange activity by microtubules. This portion of the
      protein includes a coiled-coil motif, a proline-rich motif that may interact with
      Src homology 3 domain-containing proteins, and a potential binding site for 14-3
      3 proteins. We identify GEF-H1 as a binding target and substrate for p21
      activated kinase 1 (PAK1), an effector of Rac and Cdc42 GTPases, using an
      affinity-based screen and localize a PAK1 phosphorylation site to the inhibitory
      carboxyl-terminal region of GEF-H1. We show that phosphorylation of GEF-H1 at
      Ser(885) by PAK1 induces 14-3-3 binding to the exchange factor and relocation of
      14-3-3 to microtubules. Phosphorylation of GEF-H1 by PAK may be involved in
      regulation of GEF-H1 activity and may serve to coordinate Rho-, Rac-, and Cdc42
      mediated signaling pathways.

PMID- 14970202
TI  - Functional coupling of rat myometrial alpha 1-adrenergic receptors to Gh
      alpha/tissue transglutaminase 2 during pregnancy.
AB  - Gh alpha protein, which exhibits both transglutaminase and GTPase activities,
      represents a new class of GTP-binding proteins. In the present study, we
      characterized Gh alpha in rat uterine smooth muscle (myometrium) and followed its
      expression during pregnancy by reverse transcription-PCR and Western blot. We
      also measured transglutaminase and GTP binding functions and used a smooth muscle
      cell line to evaluate the role of Gh alpha in cell proliferation. The results
      show that pregnancy is associated with an up-regulation of Gh alpha expression at
      both the mRNA and protein level. Gh alpha induced during pregnancy is
      preferentially localized to the plasma membrane. This was found associated with
      an increased ability of plasma membrane preparations to catalyze Ca(2+)-dependent
      incorporation of [(3)H]putrescine into casein in vitro. In the cytosol,
      significant changes in the level of immunodetected Gh alpha and transglutaminase
      activity were seen only at term. Activation of alpha1-adrenergic receptors
      (alpha1-AR) enhanced photoaffinity labeling of plasma membrane Gh alpha.
      Moreover, the level of alpha1-AR-coupled Gh alpha increased progressively with
      pregnancy, which parallels the active period of myometrial cell proliferation.
      Overexpression of wild type Gh alpha in smooth muscle cell line DDT1-MF2
      increased alpha1-AR-induced [(3)H]thymidine incorporation. A similar response was
      obtained in cells expressing the transglutaminase inactive mutant (C277S) of Gh
      alpha. Together, these findings underscore the role of Gh alpha as signal
      transducer of alpha1-AR-induced smooth muscle cell proliferation. In this
      context, pregnant rat myometrium provides an interesting physiological model to
      study the mechanisms underlying the regulation of the GTPase function of Gh alpha

PMID- 14970203
TI  - RasGRP1 sensitizes an immature B cell line to antigen receptor-induced apoptosis.
AB  - RasGRP1 is a guanine nucleotide exchange factor that activates Ras GTPases and is
      activated downstream of antigen receptors on both T and B lymphocytes. Ras-GRP1
      provides signals to immature T cells that confer survival and proliferation, but
      RasGRP1 also promotes T cell receptor-mediated deletion of mature T cells. We
      used the WEHI-231 cell line as an experimental system to determine whether
      RasGRP1 can serve as a quantitative modifier of B cell receptor-induced deletion
      of immature B cells. A 2-fold elevation in RasGRP1 expression markedly increased
      apoptosis of WEHI-231 cells following B cell receptor ligation, whereas a
      dominant negative mutant of RasGRP1 suppressed B cell receptor-induced apoptosis.
      Activation of ERK1 or ERK2 kinases was not required for RasGRP1-mediated
      apoptosis. Instead, elevated RasGRP1 expression caused down-regulation of NF
      kappaB and Bcl-x(L), which provide survival signals counter-acting apoptosis
      induction by B cell receptor. Inhibition of NF-kappaB was sufficient to enhance B
      cell receptor-induced apoptosis of WEHI-231 cells, and ligation of co-stimulatory
      receptors that activate NF-kappaB suppressed the ability of RasGRP1 to promote B
      cell receptor-induced apoptosis. These experiments define a novel apoptosis
      promoting pathway leading from B cell receptor to the inhibition of NF-kappaB and
      demonstrate that differential expression of RasGRP1 has the potential to modulate
      the sensitivities of B cells to negative selection following antigen encounter.

PMID- 14970204
TI  - Regulation of the neuron-specific Ras GTPase-activating protein, synGAP, by
      Ca2+/calmodulin-dependent protein kinase II.
AB  - synGAP is a neuron-specific Ras GTPase-activating protein found in high
      concentration in the postsynaptic density fraction from mammalian forebrain.
      Proteins in the postsynaptic density, including synGAP, are part of a signaling
      complex attached to the cytoplasmic tail of the N-methyl-d-aspartate-type
      glutamate receptor. synGAP can be phosphorylated by a second prominent component
      of the complex, Ca(2+)/calmodulin-dependent protein kinase II. Here we show that
      phosphorylation of synGAP by Ca(2+)/calmodulin-dependent protein kinase II
      increases its Ras GTPase-activating activity by 70-95%. We identify four major
      sites of phosphorylation, serines 1123, 1058, 750/751/756, and 764/765. These
      sites together with other minor phosphorylation sites in the carboxyl tail of
      synGAP control stimulation of GTPase-activating activity. When three of these
      sites and four other serines in the carboxyl tail are mutated, stimulation of GAP
      activity after phosphorylation is reduced to 21 +/- 5% compared with 70-95% for
      the wild type protein. We used phosphosite-specific antibodies to show that, as
      predicted, phosphorylation of serines 765 and 1123 is increased in cultured
      cortical neurons after exposure of the neurons to the agonist N-methyl-d
      aspartate.

PMID- 14970205
TI  - Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up
      regulation of beclin 1.
AB  - The sphingolipid ceramide is involved in the cellular stress response. Here we
      demonstrate that ceramide controls macroautophagy, a major lysosomal catabolic
      pathway. Exogenous C(2)-ceramide stimulates macroautophagy (proteolysis and
      accumulation of autophagic vacuoles) in the human colon cancer HT-29 cells by
      increasing the endogenous pool of long chain ceramides as demonstrated by the use
      of the ceramide synthase inhibitor fumonisin B(1). Ceramide reverted the
      interleukin 13-dependent inhibition of macroautophagy by interfering with the
      activation of protein kinase B. In addition, C(2)-ceramide stimulated the
      expression of the autophagy gene product beclin 1. Ceramide is also the mediator
      of the tamoxifen-dependent accumulation of autophagic vacuoles in the human
      breast cancer MCF-7 cells. Monodansylcadaverine staining and electron microscopy
      showed that this accumulation was abrogated by myriocin, an inhibitor of de novo
      synthesis ceramide. The tamoxifen-dependent accumulation of vacuoles was mimicked
      by 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of
      glucosylceramide synthase. 1-Phenyl-2-decanoylamino-3-morpholino-1-propanol,
      tamoxifen, and C(2)-ceramide stimulated the expression of beclin 1, whereas
      myriocin antagonized the tamoxifen-dependent up-regulation. Tamoxifen and C(2)
      ceramide interfere with the activation of protein kinase B, whereas myriocin
      relieved the inhibitory effect of tamoxifen. In conclusion, the control of
      macroautophagy by ceramide provides a novel function for this lipid mediator in a
      cell process with major biological outcomes.

PMID- 14970206
TI  - Specific structural requirements for the inhibitory effect of thapsigargin on the
      Ca2+ ATPase SERCA.
AB  - Mutational analysis of amino acid residues lining the thapsigargin (TG) binding
      cavity at the interface of the membrane surface and cytosolic headpiece was
      performed in the Ca(2+) ATPase (SERCA-1). Specific mutations such as F256V,
      I765A, and Y837A reduce not only the apparent affinity of the ATPase for TG but
      also the maximal inhibitory effect. The effect of mutations is dependent on the
      type and size of the substitute side chain, indicating that hydrophobic
      partitioning of TG and complementary molecular shapes are involved not only in
      binding but also in the inhibitory mechanism. A major factor determining the
      inhibitory effect of bound TG is its interference with conformational changes
      that are required for the progress of the ATPase cycle. Most prominent and
      specific is the TG interference with a wide displacement of the Phe-256 side
      chain that is associated with the E2 to E1.2Ca(2+) transition. The specificity of
      the TG inhibitory mechanism is emphasized by the finding that the F256V mutation
      does not interfere at all with the effect of 2,5-di-(t-butyl)-hydroquinone, which
      is another SERCA inhibitor bound by hydrophobic partitioning. The specificity of
      the inhibitory mechanism is also emphasized by the observation that within the
      concentration range producing total inhibition of wild-type SERCA-1, TG produces
      a 4-fold stimulation of the P-glycoprotein (multidrug transporter) ATPase.

PMID- 14970207
TI  - Solution structure of the pore-forming protein of Entamoeba histolytica.
AB  - Amoebapore A is a 77-residue protein from the protozoan parasite and human
      pathogen Entamoeba histolytica. Amoebapores lyse both bacteria and eukaryotic
      cells by pore formation and play a pivotal role in the destruction of host
      tissues during amoebiasis, one of the most life-threatening parasitic diseases.
      Amoebapore A belongs to the superfamily of saposin-like proteins that are
      characterized by a conserved disulfide bond pattern and a fold consisting of five
      helices. Membrane-permeabilizing effector molecules of mammalian lymphocytes such
      as porcine NK-lysin and the human granulysin share these structural attributes.
      Several mechanisms have been proposed to explain how saposin-like proteins form
      membrane pores. All mechanisms indicate that the surface charge distribution of
      these proteins is the basis of their membrane binding capacity and pore
      formation. Here, we have solved the structure of amoebapore A by NMR
      spectroscopy. We demonstrate that the specific activation step of amoebapore A
      depends on a pH-dependent dimerization event and is modulated by a surface
      exposed histidine residue. Thus, histidine-mediated dimerization is the molecular
      switch for pore formation and reveals a novel activation mechanism of pore
      forming toxins.

PMID- 14970208
TI  - Human fibroblasts with mutations in COL5A1 and COL3A1 genes do not organize
      collagens and fibronectin in the extracellular matrix, down-regulate alpha2beta1
      integrin, and recruit alphavbeta3 Instead of alpha5beta1 integrin.
AB  - Dermal fibroblasts derived from types I and IV Ehlers-Danlos syndrome (EDS)
      patients, carrying mutations in COL5A1 and COL3A1 genes, respectively, synthesize
      aberrant types V and III collagen (COLL) and show defective organization of these
      proteins into the extracellular matrix (ECM) and high reduction of their
      functional receptor, the alpha(2)beta(1) integrin, compared with control
      fibroblasts. EDS cells also show reduced levels of fibronectin (FN) in the
      culture medium and lack an FN fibrillar network. Finally, EDS cells prevalently
      organize alpha(v)beta(3) integrin instead of alpha(5)beta(1) integrin. The
      alpha(v)beta(3) integrin, distributed on the whole EDS cell surface, shows FN
      binding and assembly properties when the cells are treated with purified FN.
      Treatment of EDS cells with purified COLLV or COLLIII, but not with FN, restores
      the control phenotype (COLL(+), FN(+), alpha(v)beta(3)(-), alpha(5)beta(1)(+),
      alpha(2)beta(1)(+)). Function-blocking antibodies to COLLV, COLLIII, or
      alpha(2)beta(1) integrin induce in control fibroblasts an EDS-like phenotype
      (COLL(-), FN(-), alpha(v)beta(3)(+), alpha(5)beta(1)(-), alpha(2)beta(1)(-)).
      These results show that in human fibroblasts alpha(2)beta(1) integrin
      organization and function are controlled by its ligand, and that the
      alpha(2)beta(1)-COLL interaction, in turn, regulates FN integrin receptor
      recruitment: high alpha(2)beta(1) integrin levels induce alpha(5)beta(1) integrin
      organization, while low alpha(2)beta(1) integrin levels lead to alpha(v)beta(3)
      integrin organization.

PMID- 14970209
TI  - TAZ interacts with TTF-1 and regulates expression of surfactant protein-C.
AB  - Thyroid transcription factor-1 (TTF-1/Nkx-2.1) is required for formation of the
      lung and differentiation of peripheral respiratory epithelial cells. TTF-1
      activates transcription of target genes, including the surfactant proteins
      critical for lung function. A recently identified protein TAZ (transcriptional co
      activator with PDZ-binding motif) contains a WW domain and a COOH-terminal PDZ
      binding motif that are proposed to mediate its interactions with various
      transcriptional proteins. To determine the role of TAZ in the regulation of gene
      expression in the lung, the sites of TAZ expression and the role of TAZ in the
      regulation of respiratory epithelial gene expression were assessed. TAZ mRNA was
      detected in immortalized mouse lung epithelial cells, primary isolates of mouse
      alveolar type II epithelial cells, and epithelial cells of fetal lung. Sites of
      TAZ mRNA and protein overlapped with those of TTF-1 and surfactant protein C (SP
      C) in the respiratory epithelial cells of the mouse lung. In the presence of TTF
      1, TAZ synergistically activated the expression of mouse SP-C-luciferase reporter
      constructs. Mammalian two-hybrid assays and pull-down experiments demonstrated
      that the TAZ directly interacted with TTF-1. Further, deletion analysis
      demonstrated that TAZ binds to the NH(2)-terminal domain of TTF-1. TAZ binds to
      TTF-1, increasing the transcriptional activity of TTF-1 on the SP-C promoter.
      Developmental and cell-selective regulation of TAZ provides a mechanism by which
      the activity of TTF-1 on target genes is modulated.

PMID- 14970210
TI  - Cdc42-dependent mediation of UV-induced p38 activation by G protein betagamma
      subunits.
AB  - The beta and gamma subunits of heterotrimeric GTP-binding proteins (Gbetagamma)
      were found to bi-directionally regulate the UV-induced activation of p38 and c
      Jun NH(2)-terminal kinase, and the UV-induced activation of p38 was reported to
      enhance the resistance of normal keratinocytes to apoptosis. However, the
      signaling pathway downstream of Gbetagamma for this UV-induced p38 activation is
      not known. Thus, we examined the role of the Rho GTPase family in the regulation
      of UV-induced p38 activation by Gbetagamma. We found that overexpression of
      Gbetagamma increased the UV-induced activation of Cdc42 and that overexpression
      of constitutively active V12 Cdc42 increased the UV-induced p38 activation.
      Transfection of dominant negative N17 Cdc42 or small interfering RNA for Cdc42
      blocked UV-induced p38 activation mediated by Gbetagamma in COS-1 and HaCaT
      cells. UV-induced p38 activation by Gbetagamma was blocked by overexpression of
      dominant negative p21-activated kinase (PAK)-interacting exchange factor beta
      (betaPix), and wild type betaPix stimulated the UV-induced p38 activation, which
      was blocked by N17 Cdc42. Gbetagamma increased the UV-induced activation of Ras,
      and the overexpression of V12 Ras increased UV-induced p38 activation, which was
      blocked by dominant negative betaPix. UV-induced p38 activation was inhibited by
      N17 Ras and a farnesyltransferase inhibitor, manumycin A. Gbetagamma also
      increased the UV-induced phosphorylation of the epidermal growth factor receptor
      (EGFR), and the UV-induced p38 activation was blocked by an EGFR kinase
      inhibitor, AG1478. From these results, we conclude that Gbetagamma mediates UV
      induced activation of p38 in a Cdc42-dependent way and that EGFR, Ras, and
      betaPix act sequentially upstream of Cdc42 in COS-1 and HaCaT cells.

PMID- 14970211
TI  - Facilitation of stress-induced phosphorylation of beta-amyloid precursor protein
      family members by X11-like/Mint2 protein.
AB  - Beta-amyloid precursor protein (APP) is the precursor of beta-amyloid (Abeta),
      which is implicated in Alzheimer's disease pathogenesis. APP complements amyloid
      precursor-like protein 2 (APLP2), and together they play essential physiological
      roles. Phosphorylation at the Thr(668) residue of APP (with respect to the
      numbering conversion for the APP 695 isoform) and the Thr(736) residue of APLP2
      (with respect to the numbering conversion for the APLP2 763 isoform) in their
      cytoplasmic domains acts as a molecular switch for their protein-protein
      interaction and is implicated in neural function(s) and/or Alzheimer's disease
      pathogenesis. Here we demonstrate that both APP and APLP2 can be phosphorylated
      by JNK at the Thr(668) and Thr(736) residues, respectively, in response to
      cellular stress. X11-like (X11L, also referred to as X11beta and Mint2), which is
      a member of the mammalian LIN-10 protein family and a possible regulator of Abeta
      production, elevated APP and APLP2 phosphorylation probably by facilitating JNK
      mediated phosphorylation, whereas other members of the family, X11 and X11L2, did
      not. These observations revealed an involvement of X11L in the phosphorylation of
      APP family proteins in cellular stress and suggest that X11L protein may be
      important in the physiology of APP family proteins as well as in the regulation
      of Abeta production.

PMID- 14970212
TI  - The proteolytic processing of the amyloid precursor protein gene family members
      APLP-1 and APLP-2 involves alpha-, beta-, gamma-, and epsilon-like cleavages:
      modulation of APLP-1 processing by n-glycosylation.
AB  - Amyloid precursor protein (APP) processing is of major interest in Alzheimer's
      disease research, since sequential cleavages by beta- and gamma-secretase lead to
      the formation of the 4-kDa amyloid Abeta protein peptide that accumulates in
      Alzheimer's disease brain. The processing of APP involves proteolytic conversion
      by different secretases leading to alpha-, beta-, gamma-, delta-, and epsilon
      cleavages. Since modulation of these cleavages represents a rational therapeutic
      approach to control amyloid formation, its interference with the processing of
      the members of the APP gene family is of considerable importance. By using C
      terminally tagged constructs of APLP-1 and APLP-2 and the untagged proteins, we
      have characterized their proteolytic C-terminal fragments produced in stably
      transfected SH-SY5Y cells. Pharmacological manipulation with specific protease
      inhibitors revealed that both homologues are processed by alpha- and gamma
      secretase-like cleavages, and that their intracellular domains can be released by
      cleavage at epsilon-sites. APLP-2 processing appears to be the most elaborate and
      to involve alternative cleavage sites. We show that APLP-1 is the only member of
      the APP gene family for which processing can be influenced by N-glycosylation.
      Additionally, we were able to detect p3-like fragments of APLP-1 and p3-like and
      Abeta-like fragments of APLP-2 in the media of stably transfected SH-SY5Y cells.

PMID- 14970213
TI  - Functional dissection of RNA polymerase III termination using a peptide nucleic
      acid as a transcriptional roadblock.
AB  - We have shown previously that a T(10) peptide nucleic acid (PNA) bound to the
      transcriptional terminator of a Saccharomyces cerevisiae tDNA(Ile)(TAT) gene
      arrests elongating yeast RNA polymerase (pol) III at a position that precedes by
      20 bp the upstream end of the PNA roadblock (Dieci, G., Corradini, R., Sforza,
      S., Marchelli, R., and Ottonello, S. (2001) J. Biol. Chem. 276, 5720-5725). Here,
      a PNA-binding cassette was placed at various distances downstream of a functional
      tDNA(Ile) transcriptional terminator (T(6)) that is not bound by the T(10) PNA,
      and the effect of the PNA roadblock on RNA 3'-end formation, transcript release,
      and transcription reinitiation was examined. With a PNA roadblock placed as close
      as 5 bp downstream of the T(6) terminator, pol III could still reach the
      termination site and complete pre-tRNA synthesis, implying that the catalytic
      site-to-front edge (C-F) distance of the polymerase can shorten by >10 bp upon
      recognition of the terminator element. In addition, transcripts synthesized by a
      PNA-roadblocked terminating pol III were found to be released from transcription
      complexes. Interestingly, however, the same roadblock dramatically reduced the
      rate of transcription reinitiation. Also, when placed 5 bp downstream of a
      mutationally inactivated terminator element (T(3)GT(2)), the PNA roadblock
      restored transcription termination, thus indicating that the inactivated
      terminator is compromised in its ability to cause pol III pausing, but can still
      induce C-F distance shortening and transcript release. The latter two activities
      were found to be further impaired in variants of the inactivated terminator
      bearing fewer than three consecutive T residues (T(2)G(2)T(2) and TG(2)TGT). The
      data indicate that RNA polymerase pausing, C-F distance shortening, and
      transcript release are functionally distinguishable features of the termination
      process and point to the RNA release propensity of pol III as a major determinant
      of its remarkably high termination efficiency.

PMID- 14970214
TI  - The Escherichia coli NADH:ubiquinone oxidoreductase (complex I) is a primary
      proton pump but may be capable of secondary sodium antiport.
AB  - The NADH:ubiquinone oxidoreductase (complex I) couples the transfer of electrons
      from NADH to ubiquinone with the translocation of protons across the membrane.
      Recently, it was demonstrated that complex I from Klebsiella pneumoniae
      translocates sodium ions instead of protons. Experimental evidence suggested that
      complex I from the close relative Escherichia coli works as a primary sodium pump
      as well. However, data obtained with whole cells showed the presence of an NADH
      induced electrochemical proton gradient. In addition, Fourier transform IR
      spectroscopy demonstrated that the redox reaction of the E. coli complex I is
      coupled to a protonation of amino acids. To resolve this contradiction we
      measured the properties of isolated E. coli complex I reconstituted in
      phospholipids. We found that the NADH:ubiquinone oxidoreductase activity did not
      depend on the sodium concentration. The redox reaction of the complex in
      proteoliposomes caused a membrane potential due to an electrochemical proton
      gradient as measured with fluorescent probes. The signals were sensitive to the
      protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP), the inhibitors
      piericidin A, dicyclohexylcarbodi-imide (DCCD), and amiloride derivatives, but
      were insensitive to the sodium ionophore ETH-157. Furthermore, monensin acting as
      a Na(+)/H(+) exchanger prevented the generation of a proton gradient. Thus, our
      data demonstrated that the E. coli complex I is a primary electrogenic proton
      pump. However, the magnitude of the pH gradient depended on the sodium
      concentration. The capability of complex I for secondary Na(+)/H(+) antiport is
      discussed.

PMID- 14970215
TI  - Stimulus-specific differences in protein kinase C delta localization and
      activation mechanisms in cardiomyocytes.
AB  - Protein kinase C (PKC) isoforms play key roles in the regulation of cardiac
      contraction, ischemic preconditioning, and hypertrophy/failure. Models of PKC
      activation generally focus on lipid cofactor-induced PKC translocation to
      membranes. This study identifies tyrosine phosphorylation as an additional
      mechanism that regulates PKC delta actions in cardiomyocytes. Using immunoblot
      analysis with antibodies to total PKC delta and PKC delta-pY(311), we demonstrate
      that PKC delta partitions between soluble and particulate fractions (with little
      Tyr(311) phosphorylation) in resting cardiomyocytes. Phorbol 12-myristate 13
      acetate (PMA) promotes PKC delta translocation to membranes and phosphorylation
      at Tyr(311). H(2)O(2) also increases PKC delta-pY(311) in association with its
      release from membranes. Both PMA- and H(2)O(2)-dependent increases in PKC delta
      pY(311) are mediated by Src family kinases, but they occur via different
      mechanisms. The H(2)O(2)-dependent increase in PKC delta-pY(311) results from Src
      activation and increased Src-PKC delta complex formation. The PMA-dependent
      increase in PKC delta-pY(311) results from a lipid cofactor-induced
      conformational change that renders PKC delta a better substrate for
      phosphorylation by precomplexed Src kinases (without Src activation). PKC delta
      Y(311) phosphorylation does not grossly alter the kinetics of PMA-dependent PKC
      delta down-regulation. Rather, tyrosine phosphorylation regulates PKC delta
      kinase activity. PKC delta is recovered from the soluble fraction of H(2)O(2)
      treated cardiomyocytes as a tyrosine-phosphorylated, lipid-independent enzyme
      with altered substrate specificity. In vitro PKC delta phosphorylation by Src
      also increases lipid-independent kinase activity. The magnitude of this effect
      varies, depending upon the substrate, suggesting that tyrosine phosphorylation
      fine-tunes PKC delta substrate specificity. The stimulus-specific modes for PKC
      delta signaling identified in this study allow for distinct PKC delta-mediated
      phosphorylation events and responses during growth factor stimulation and oxidant
      stress in cardiomyocytes.

PMID- 14970216
TI  - Proteasomal degradation of the nuclear targeting growth factor midkine.
AB  - It is widely held that growth factor signaling is terminated by lysosomal
      degradation of its activated receptor and the endocytosed growth factor is
      transported to lysosomes. Nuclear targeting is another important pathway through
      which signals of growth factors are mediated. However, mechanisms underlying
      desensitization of nuclear targeting growth factors are poorly understood. Here
      we report that the nuclear targeting pathway is down-regulated by the proteasome
      system. Degradation of endocytosed midkine, a heparin-binding growth factor, was
      suppressed by both proteasome and lysosome inhibitors to similar extents. By
      contrast, a proteasome inhibitor, but not lysosome ones, accelerated the nuclear
      accumulation of midkine. An expression vector of signal sequence-less midkine,
      which is produced in the cytosol, was constructed because endocytosed midkine may
      be translocated to the cytosol from cellular compartments before entering the
      nucleus. The cytosol-produced midkine underwent proteasomal degradation and
      accumulated in the nucleus as did the endocytosed midkine. It was
      polyubiquitinated, and its nuclear accumulation was enhanced by a proteasome
      inhibitor. We further dissected the midkine molecule to investigate roles in
      degradation and trafficking. The N-terminal half-domain of midkine was
      significantly more susceptible to proteasomal degradation, whereas the C-terminal
      half-domain was sufficient for nuclear localization. Together, these data
      highlight the desensitization of nuclear targeting by growth factors and indicate
      a critical role of the proteasome system in it.

PMID- 14970217
TI  - Nucleotide binding induces conformational changes in Escherichia coli
      transcription termination factor Rho.
AB  - The Escherichia coli Rho protein uses the energy of ATP binding and hydrolysis to
      translocate along RNA and cause transcription termination. Using fluorescence
      stopped-flow kinetic studies, we have discerned the conformational changes in the
      Rho protein that occur upon nucleotide and nucleic acid binding. We show that the
      2', (3')-O-[N-methylanthraniloyl] derivative of ATP (mant-ATP) is a good
      fluorescent substrate of Rho and is hydrolyzed with a K(m) comparable with that
      for ATP but a k(cat) five to six times slower than that for ATP. The kinetics of
      ATP and mant-ATP binding indicates that, in the absence of RNA, the Rho protein
      is structurally distinct from the Rho hexamer found when bound to RNA or DNA. In
      the absence of RNA, the nucleotide-binding rates are 50- to 70-fold slower, and
      the dissociation rates are 40- to 120-fold slower than the corresponding rates in
      the presence of RNA. We conclude that RNA or DNA binding to the primary nucleic
      acid binding sites causes conformational changes in the Rho hexamer that result
      in the opening of the subunit interfaces. Furthermore, the kinetic studies
      revealed a unique protein conformational change in the Rho.RNA complex upon ATP
      binding that is a result of RNA contacting the secondary nucleic acid binding
      sites in the central channel of the Rho ring. This conformational change seems to
      render the Rho ring competent in ATP hydrolysis and translocation.

PMID- 14970218
TI  - Isoforms of the Ets transcription factor NERF/ELF-2 physically interact with AML1
      and mediate opposing effects on AML1-mediated transcription of the B cell
      specific blk gene.
AB  - We previously isolated different isoforms of a new Ets transcription factor
      family member, NERF/ELF-2, NERF-2, NERF-1a, and NERF-1b. In contrast to the
      inhibitory isoforms NERF-1a and NERF-1b, NERF-2 acts as a transactivator of the B
      cell-specific blk promoter. We now report that NERF-2 and NERF-1 physically
      interact with AML1 (RUNX1), a frequent target for chromosomal translocations in
      leukemia. NERF-2 bound to AML1 via an interaction site located in a basic region
      upstream of the Ets domain. This is in contrast to most other Ets factors such as
      Ets-1 that bind to AML1 via the Ets domain, suggesting that different Ets factors
      utilize different domains for interaction with AML1. The interaction between AML1
      and NERF-2 led to cooperative transactivation of the blk promoter, whereas the
      interaction between AML1 and NERF-1a led to repression of AML1-mediated
      transactivation. To delineate the differences in function of the different NERF
      isoforms, we determined that the transactivation domain of NERF-2 is encoded by
      the N-terminal 100 amino acids, which have been replaced in NERF-1a by a 19-amino
      acid transcriptionally inactive sequence. Furthermore, acidic domains A and B,
      which are conserved in NERF-2 and the related proteins ELF-1 and MEF/ELF-4, but
      not in NERF-1a, are largely responsible for NERF-2-mediated transactivation.
      Because translocation of the Ets factor Tel to AML1 is a frequent event in
      childhood pre-B leukemia, understanding the interaction of Ets factors with AML1
      in the context of a B cell-specific promoter might help to determine the function
      of Ets factors and AML1 in leukemia.

PMID- 14970219
TI  - IQGAP1 binds ERK2 and modulates its activity.
AB  - IQGAP1 binds several proteins including actin, calmodulin, E-cadherin, beta
      catenin, Cdc42, Rac1, and CLIP-170. The interaction with these targets enables
      IQGAP1 to participate in many cellular functions varying from regulation of the
      cytoskeleton to gene transcription. Here we show that extracellular signal
      regulated kinase (ERK) 2 binds to IQGAP1. In vitro analysis with purified
      proteins demonstrated a direct interaction between ERK2 and IQGAP1. Moreover,
      binding occurred in cells as endogenous ERK2 co-immunoprecipitated with IQGAP1
      from human breast epithelial cell lysates. The association between ERK2 and
      IQGAP1 was independent of epidermal growth factor. The in vivo interaction has
      functional significance. Manipulation of intracellular IQGAP1 levels
      significantly reduced growth factor-stimulated ERK1 and ERK2 activity. Similarly,
      stimulation of ERK1 and ERK2 activity by insulin-like growth factor I was reduced
      when IQGAP1 levels were changed. In contrast, overexpression of an IQGAP1
      construct lacking the ERK2 binding region did not interfere with activation of
      ERK1 and ERK2 by epidermal growth factor. Our data disclose a previously
      unidentified communication between IQGAP1 and the ERK pathway and imply that
      IQGAP1 modulates the Ras/mitogen-activated protein kinase signaling cascade.

PMID- 14970220
TI  - Rho is involved in superoxide formation during phagocytosis of opsonized
      zymosans.
AB  - Phagocytosis is accompanied by the production of superoxide by the NADPH oxidase
      complex, for which GTP-bound Rac is essential. We wanted to determine whether Rho
      is also involved in the production of superoxide during phagocytosis. Inhibition
      of Rho by Tat-C3 exoenzyme (Tat-C3) blocked superoxide formation and curtailed
      the phagocytosis of serum- (SOZ), C3bi- (COZ), and IgG-opsonized zymosan (IOZ)
      particles. Tat-C3 did not affect superoxide formation in response to phorbol
      myristate acetate (PMA), formyl Met-Leu-Phe (fMLP), or macrophage colony
      stimulating factor (M-CSF). Superoxide formation was also reduced in J774 cells
      transfected with a cDNA expressing dominant-negative form of RhoA (N19RhoA).
      However, purified prenylated recombinant RhoA did not activate NADPH oxidase in
      vitro, suggesting that Rho does not interact directly with NADPH oxidase. Tat-C3
      inhibited the activity of RhoA, but did not affect that of Rac in vitro or in
      vivo. It also inhibited the phosphorylation of p47(PHOX), one of the cytosolic
      components of NADPH oxidase. Taken together, these results suggest that Rho plays
      an important role in superoxide formation during phagocytosis of SOZ, COZ, and
      IOZ via phosphorylation of p47(PHOX).

PMID- 14970221
TI  - Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site
      regulated by nutrient status.
AB  - The mammalian target of rapamycin (mTOR) is a key regulator of protein
      translation. Signaling via mTOR is increased by growth factors but decreased
      during nutrient deprivation. Previous studies have identified Ser2448 as a
      nutrient-regulated phosphorylation site located in the mTOR catalytic domain,
      insulin stimulates Ser2448 phosphorylation via protein kinase B (PKB), while
      Ser2448 phosphorylation is attenuated with amino acid starvation. Here we have
      identified Thr2446 as a novel nutrient-regulated phosphorylation site on mTOR.
      Thr2446 becomes phosphorylated when CHO-IR cells are nutrient-deprived, but
      phosphorylation is reduced by insulin stimulation. Nutrient deprivation activates
      AMP-activated protein kinase (AMPK). To test whether this could be involved in
      regulating phoshorylation of mTOR, we treated cultured murine myotubes with 5'
      aminoimidazole-4-carboxamide ribonucleoside (AICAR) or dinitrophenol (DNP). Both
      treatments activated AMPK and also caused a concomitant increase in
      phosphorylation of Thr2446 and a parallel decrease in insulin's ability to
      phosphorylate p70 S6 kinase. In vitro kinase assays using peptides based on the
      sequence in amino acids 2440-2551 of mTOR found that PKB and AMPK are capable of
      phosphorylating sites in this region. However, phosphorylation by PKB is
      restricted when Thr2446 is mutated to an acidic residue mimicking
      phosphorylation. Conversely, AMP-kinase-induced phosphorylation is reduced when
      Ser2448 is phosphorylated. These data suggest differential phosphorylation
      Thr2446 and Ser2448 could act as a switch mechanism to integrate signals from
      nutrient status and growth factors to control the regulation of protein
      translation.

PMID- 14970222
TI  - The specificities of four yeast dihydrouridine synthases for cytoplasmic tRNAs.
AB  - Dihydrouridine is a highly abundant modified nucleoside found widely in tRNAs of
      eubacteria, eukaryotes, and some archaea. In cytoplasmic tRNA of Saccharomyces
      cerevisiae, dihydrouridine occurs exclusively at positions 16, 17, 20, 20A, 20B,
      and 47. Here we show that the known dihydrouridine synthases Dus1p and Dus2p and
      two previously uncharacterized homologs, Dus3p (encoded by YLR401c) and Dus4p
      (YLR405w), are required for all of the dihydrouridine modification of cytoplasmic
      tRNAs in S. cerevisiae. We have mapped the in vivo position specificity of the
      four Dus proteins, by three complementary approaches: determination of the molar
      ratio of dihydrouridine in purified tRNAs from different dus mutants; microarray
      analysis of a large number of tRNAs based on differential hybridization of
      uridine and dihydrouridine-containing tRNAs to the complementary
      oligonucleotides; and the development and use of a novel dihydrouridine mapping
      technique, employing primer extension. We show that each of the four Dus proteins
      has a distinct position specificity: Dus1p for U(16) and U(17), Dus2p for U(20),
      Dus3p for U(47), and Dus4p for U(20a) and U(20b).

PMID- 14970223
TI  - Loss of the intermembrane space protein Mgm1/OPA1 induces swelling and localized
      constrictions along the lengths of mitochondria.
AB  - Mgm1 is a member of the dynamin family of GTP-binding proteins. Mgm1 was first
      identified in yeast, where it affects mitochondrial morphology. The human
      homologue of Mgm1 is called OPA1. Mutations in the OPA1 gene are the prevailing
      cause of dominant optic atrophy, a hereditary disease in which progressive
      degeneration of the optic nerve can lead to blindness. Here we investigate the
      properties of the Mgm1/OPA1 protein in mammalian cells. We find that Mgm1/OPA1 is
      localized to the mitochondrial intermembrane space, where it is tightly bound to
      the outer surface of the inner membrane. Overexpression of wild type or mutant
      forms of the Mgm1/OPA1 protein cause mitochondria to fragment and, in some cases,
      cluster near the nucleus, whereas the loss of protein caused by small interfering
      RNA (siRNA) leads to dispersal of mitochondrial fragments throughout the cytosol.
      The cristae of these fragmented mitochondria are disorganized. At early time
      points after transfection with Mgm1/OPA1 siRNA, the mitochondria are not yet
      fragmented. Instead, the mitochondria swell and stretch, after which they form
      localized constrictions similar to the mitochondrial abnormalities observed
      during the early stages of apoptosis. These abnormalities might be the earliest
      effects of losing Mgm1/OPA1 protein.

PMID- 14970224
TI  - The plasma membrane-associated sialidase MmNEU3 modifies the ganglioside pattern
      of adjacent cells supporting its involvement in cell-to-cell interactions.
AB  - We describe herein the enzyme behavior of MmNEU3, the plasma membrane-associated
      sialidase from mouse (Mus musculus). MmNEU3 is localized at the plasma membrane
      as demonstrated directly by confocal microscopy analysis. In addition,
      administration of the radiolabeled ganglioside GD1a to MmNEU3-transfected cells,
      under conditions that prevent lysosomal activity, led to its hydrolysis into
      ganglioside GM1, further indicating the plasma membrane topology of MmNEU3.
      Metabolic labeling with [1-(3)H]sphingosine allowed the characterization of the
      ganglioside patterns of COS-7 cells. MmNEU3 expression in COS-7 cells led to an
      extensive modification of the cell ganglioside pattern, i.e. GM3 and GD1a content
      was decreased to about one-third compared with mock-transfected cells. At the
      same time, a 35% increase in ganglioside GM1 content was observed. Mixed culture
      of MmNEU3-transfected cells with [1-(3)H]sphingosine-labeled cells demonstrates
      that the enzyme present at the cell surface is able to recognize gangliosides
      exposed on the membrane of nearby cells. Under these experimental conditions, the
      extent of ganglioside pattern changes was a function of MmNEU3 transient
      expression. Overall, the variations in GM3, GD1a, and GM1 content were very
      similar to those observed in the case of [1-(3)H]sphingosine-labeled MmNEU3
      transfected cells, indicating that the enzyme mainly exerted its activity toward
      ganglioside substrates present at the surface of neighboring cells. These results
      indicate that the plasma membrane-associated sialidase MmNEU3 is able to
      hydrolyze ganglioside substrates in intact living cells at a neutral pH, mainly
      through cell-to-cell interactions.

PMID- 14970225
TI  - Structure-function analysis of the reactive site in the first Kunitz-type domain
      of human tissue factor pathway inhibitor-2.
AB  - Human tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type proteinase
      inhibitor that regulates a variety of serine proteinases involved in coagulation
      and fibrinolysis through their non-productive interaction with a P(1) residue
      (Arg-24) in its first Kunitz-type domain (KD1). Previous kinetic studies revealed
      that TFPI-2 was a more effective inhibitor of plasmin than several other serine
      proteinases, but the molecular basis for this specificity was unclear. In this
      study, we employed molecular modeling and mutagenesis strategies to produce
      several variants of human TFPI-2 KD1 in an effort to identify interactive site
      residues other than the P(1) Arg that contribute significantly to its inhibitory
      activity and specificity. Molecular modeling of KD1 based on the crystal
      structure of bovine pancreatic trypsin inhibitor revealed that KD1 formed a more
      energetically favorable complex with plasmin versus trypsin and/or the factor
      VIIa-tissue factor complex primarily due to strong ionic interactions between Asp
      19 (P(6)) and Arg residues in plasmin (Arg-644, Arg-719, and Arg-767), Arg-24
      (P(1)) with Asp-735 in plasmin, and Arg-29 (P(5)') with Glu-606 in plasmin. In
      addition, Leu-26 through Leu-28 (P(2)'-P(4)') in KD1 formed strong van der Waals
      contact with a hydrophobic cluster in plasmin (Phe-583, Met-585, and Phe-587).
      Mutagenesis of Asp-19, Tyr-20, Arg-24, Arg-29, and Leu-26 in KD1 resulted in
      substantial reductions in plasmin inhibitory activity relative to wild-type KD1,
      but the Asp-19 and Tyr-20 mutations revealed the importance of these residues in
      the specific inhibition of plasmin. In addition to the reactive site residues in
      the P(6)-P(5)' region of KD1, mutation of a highly conserved Phe at the P(18)'
      position revealed the importance of this residue in the inhibition of serine
      proteinases by KD1. Thus, together with the P(1) residue, the nature of other
      residues flanking the P(1) residue, particularly at P(6) and P(5)', strongly
      influences the inhibitory activity and specificity of human TFPI-2.

PMID- 14970226
TI  - DC-SIGN binds to HIV-1 glycoprotein 120 in a distinct but overlapping fashion
      compared with ICAM-2 and ICAM-3.
AB  - DC-SIGN is a C-type lectin that binds to endogenous adhesion molecules ICAM-2 and
      ICAM-3 as well as the viral envelope glycoprotein human immunodeficiency virus,
      type 1, glycoprotein (gp) 120. We wished to determine whether DC-SIGN binds
      differently to its endogenous ligands ICAM-2 and ICAM-3 versus HIV-1 gp120. We
      found that recombinant soluble DC-SIGN bound to gp120-Fc more than 100- and 50
      fold better than ICAM-2-Fc and ICAM-3-Fc, respectively. This relative difference
      was maintained using DC-SIGN expressed on three different CD4-negative cell
      lines. Although the cell surface affinity for gp120 varied by up to 4-fold on the
      cell lines examined, the affinity for gp120 was not a correlate of the ability of
      the cell line to transfer virus. Monosaccharides with equatorial 4-OH groups
      competed as well as D-mannose for gp120 binding to DC-SIGN, regardless of how the
      other hydroxyl groups were positioned. Disaccharide competitors and glycan chip
      analysis showed that DC-SIGN has a preference for oligosaccharides linked in an
      alpha-anomeric configuration. Alanine-scanning mutagenesis of DC-SIGN revealed
      that highly conserved residues that coordinate calcium (Asp-366) and/or are
      involved in both calcium and specific carbohydrate interactions (Glu-347, Asn
      349, Glu-354, and Asp-355) significantly compromised binding to all three
      ligands. Mutating non-conserved residues (Asn-311, Arg-345, Val-351, Gly-352, Glu
      353, Ser-360, Gly-361, and Asn-362) minimally affected binding except for the Asp
      367 mutant, which enhanced gp120 binding but diminished ICAM-2 and ICAM-3
      binding. Conversely, mutating the moderately conserved residue (Gly-346)
      abrogated gp120 binding but enhanced ICAM-2 and ICAM-3 binding. Thus, DC-SIGN
      appears to bind in a distinct but overlapping manner to gp120 when compared with
      ICAM-2 and ICAM-3.

PMID- 14970227
TI  - Integrin alpha5beta1 and ADAM-17 interact in vitro and co-localize in migrating
      HeLa cells.
AB  - Tumor necrosis factor (TNF) alpha-converting enzyme (TACE/ADAM-17) has diverse
      roles in the proteolytic processing of cell surface molecules and, due to its
      ability to process TNFalpha, is a validated therapeutic target for anti
      inflammatory therapies. Unlike a number of other ADAM proteins, which interact
      with integrin receptors via their disintegrin domains, there is currently no
      evidence for an ADAM-17-integrin association. By analyzing the adhesion of a
      series of cell lines with recombinant fragments of the extracellular domain of
      ADAM-17, we now demonstrate a functional interaction between ADAM-17 and
      alpha(5)beta(1) integrin in a trans orientation. Because ADAM-17-mediated
      adhesion was sensitive to RGD peptides and EDTA, and the integrin-binding site
      within ADAM-17 was narrowed down to the disintegrin/cysteine-rich region, the two
      molecules appear to have a ligand-receptor relationship mediated by the
      alpha(5)beta(1) ligand binding pocket. Intriguingly, ADAM-17 and alpha(5)beta(1)
      were found to co-localize in both membrane ruffles and focal adhesions in HeLa
      cells. When confluent HeLa cell monolayers were wounded, ADAM-17 and
      alpha(5)beta(1) redistributed to the leading edge and co-localized, which is
      suggestive of a cis orientation. We postulate that the interaction of ADAM-17
      with alpha(5)beta(1) may target or modulate its metalloproteolytic activity.

PMID- 14970228
TI  - As(III) and Sb(III) uptake by GlpF and efflux by ArsB in Escherichia coli.
AB  - The toxicity of the metalloids arsenic and antimony is related to uptake, whereas
      detoxification requires efflux. In this report we show that uptake of the
      trivalent inorganic forms of arsenic and antimony into cells of Escherichia coli
      is facilitated by the aquaglyceroporin channel GlpF and that transport of Sb(III)
      is catalyzed by the ArsB carrier protein; everted membrane vesicles accumulated
      Sb(III) with energy supplied by NADH oxidation, reflecting efflux from intact
      cells. Dissipation of either the membrane potential or the pH gradient did not
      prevent Sb(III) uptake, whereas dissipation of both completely uncoupled the
      carrier protein, suggesting that transport is coupled to either the electrical or
      the chemical component of the electrochemical proton gradient. Reciprocally,
      Sb(III) transport via ArsB dissipated both the pH gradient and the membrane
      potential. These results strongly indicate that ArsB is an antiporter that
      catalyzes metalloid-proton exchange. Unexpectedly, As(III) inhibited ArsB
      mediated Sb(III) uptake, whereas Sb(III) stimulated ArsB-mediated As(III)
      transport. We propose that the actual substrate of ArsB is a polymer of (AsO)(n),
      (SbO)(n), or a co-polymer of the two metalloids.

PMID- 14970229
TI  - Release of intact and fragmented osteocalcin molecules from bone matrix during
      bone resorption in vitro.
AB  - Osteocalcin detected from serum samples is considered a specific marker of
      osteoblast activity and bone formation rate. However, osteocalcin embedded in
      bone matrix must also be released during bone resorption. To understand the
      contribution of each type of bone cell in circulating osteocalcin levels, we used
      immunoassays detecting different molecular forms of osteocalcin to monitor bone
      resorption in vitro. Osteoclasts were obtained from rat long bones and cultured
      on bovine bone slices using osteocalcin-depleted fetal bovine serum. In addition,
      human osteoclasts differentiated from peripheral blood mononuclear cells were
      used. Both rat and human osteoclasts released osteocalcin from bovine bone into
      medium. The amount of osteocalcin increased in the presence of parathyroid
      hormone, a stimulator of resorption, and decreased in the presence of bafilomycin
      A1, an inhibitor of resorption. The amount of osteocalcin in the medium
      correlated with a well characterized marker of bone resorption, the C-terminal
      telopeptide of type I collagen (r > 0.9, p < 0.0001). The heterogeneity of
      released osteocalcin was determined using reverse phase high performance liquid
      chromatography, and several molecular forms of osteocalcin, including intact
      molecule, were identified in the culture medium. In conclusion, osteocalcin is
      released from the bone matrix during bone resorption as intact molecules and
      fragments. In addition to the conventional use as a marker of bone formation,
      osteocalcin can be used as a marker of bone resorption in vitro. Furthermore,
      bone matrix-derived osteocalcin may contribute to circulating osteocalcin levels,
      suggesting that serum osteocalcin should be considered as a marker of bone
      turnover rather than bone formation.

PMID- 14970230
TI  - The yeast vacuolar proton-translocating ATPase contains a subunit homologous to
      the Manduca sexta and bovine e subunits that is essential for function.
AB  - The yeast cwh36Delta mutant was identified in a screen for yeast mutants
      exhibiting a Vma(-) phenotype suggestive of loss of vacuolar proton-translocating
      ATPase (V-ATPase) activity. The mutation disrupts two genes, CWH36 and a recently
      identified open reading frame on the opposite strand, YCL005W-A. We demonstrate
      that disruption of YCL005W-A is entirely responsible for the Vma(-) growth
      phenotype of the cwh36Delta mutant. YCL005W-A encodes a homolog of proteins
      associated with the Manduca sexta and bovine chromaffin granule V-ATPase. The
      functional significance of these proteins for V-ATPase activity had not been
      tested, but we show that the protein encoded by YCL005W-A, which we call Vma9p,
      is essential for V-ATPase activity in yeast. Vma9p is localized to the vacuole
      but fails to reach the vacuole in a mutant lacking one of the integral membrane
      subunits of the V-ATPase. Vma9p is associated with the yeast V-ATPase complex in
      vacuolar membranes, as demonstrated by co-immunoprecipitation with known V-ATPase
      subunits and glycerol gradient fractionation of solubilized vacuolar membranes.
      Based on this evidence, we propose that Vma9p is a genuine subunit of the yeast V
      ATPase and that e subunits may be a functionally essential part of all eukaryotic
      V-ATPases.

PMID- 14970231
TI  - Mutations of hydrophobic residues in the N-terminal domain of troponin C affect
      calcium binding and exchange with the troponin C-troponin I96-148 complex and
      muscle force production.
AB  - Interactions between troponin C and troponin I play a critical role in the
      regulation of skeletal muscle contraction and relaxation. We individually
      substituted 27 hydrophobic Phe, Ile, Leu, Val, and Met residues in the regulatory
      domain of the fluorescent troponin C(F29W) with polar Gln to examine the effects
      of these mutations on: (a) the calcium binding and dynamics of troponin C(F29W)
      complexed with the regulatory fragment of troponin I (troponin I(96-148)) and (b)
      the calcium sensitivity of force production. Troponin I(96-148) was an accurate
      mimic of intact troponin I for measuring the calcium dynamics of the troponin
      C(F29W)-troponin I complexes. The calcium affinities of the troponin C(F29W)
      troponin I(96-148) complexes varied approximately 243-fold, whereas the calcium
      association and dissociation rates varied approximately 38- and approximately 33
      fold, respectively. Interestingly, the effect of the mutations on the calcium
      sensitivity of force development could be better predicted from the calcium
      affinities of the troponin C(F29W)-troponin I(96-148) complexes than from that of
      the isolated troponin C(F29W) mutants. Most of the mutations did not dramatically
      affect the affinity of calcium-saturated troponin C(F29W) for troponin I(96-148).
      However, the Phe(26) to Gln and Ile(62) to Gln mutations led to >10-fold lower
      affinity of calcium-saturated troponin C(F29W) for troponin I(96-148), causing a
      drastic reduction in force recovery, even though these troponin C(F29W) mutants
      still bound to the thin filaments. In conclusion, elucidating the determinants of
      calcium binding and exchange with troponin C in the presence of troponin I
      provides a deeper understanding of how troponin C controls signal transduction.

PMID- 14970232
TI  - Development of protein-based inhibitors of the proprotein of convertase SKI
      1/S1P: processing of SREBP-2, ATF6, and a viral glycoprotein.
AB  - Processing of membrane-bound transcription factors such as sterol regulatory
      element-binding proteins (SREBPs) and the ER-stress response factor ATF6, and
      glycoproteins of some hemorrhagic fever viruses are initiated by the proprotein
      convertase SKI-1/S1P. So far, no cellular protein-based inhibitor of the
      hydrophobic-amino acid specific SKI-1 is known. The prosegment of the basic-amino
      acid specific convertases (e.g. furin and PC5) or alpha(1)-PDX, a variant of
      alpha(1)-antitrypsin (alpha(1)-AT) exhibiting an RIPR(358) sequence at the
      reactive site loop, were shown to potently inhibit these secretory proteinases.
      Accordingly, we tested the SKI-1-inhibitory potential of various point mutants of
      either the 198 amino acid preprosegment of SKI-1-(1-198) or alpha(1)-AT.
      Transient transfections data showed that, out of numerous mutants studied, the
      R134E prosegment mutant or the alpha(1)-AT reactive site loop variants RRVL(358),
      RRYL(358) and RRIL(358) are the best specific cellular inhibitors of SKI-1. The
      observed inhibition of the processing of endogenous SREBP-2, exogenous ATF6 and a
      PDGF-A (RRLL(86)) variant were >55% and reach approximately 80% in stable
      transfectants. We also show that SKI-1 forms SDS-stable complexes with these
      alpha(1)-AT variants, but not with wild-type alpha(1)-AT or alpha(1)-PDX.
      Finally, these inhibitors were also shown to affect the processing and stability
      of the Crimean-Congo hemorrhagic fever virus glycoprotein.

PMID- 14970233
TI  - Alsin, the product of ALS2 gene, suppresses SOD1 mutant neurotoxicity through
      RhoGEF domain by interacting with SOD1 mutants.
AB  - Mutation of the ALS2 gene encoding alsin is linked to the onset of autosomal
      recessive motor neuron diseases, including juvenile-onset amyotrophic lateral
      sclerosis (ALS). Alsin long form (LF) belongs to the family of the guanine
      nucleotide exchanging factor (GEF) for small GTPases. Expression of alsin LF, but
      not alsin short form, protected motor neuronal cells from toxicity induced by
      mutants of the Cu/Zn-superoxide dismutase (SOD1) gene, which cause autosomal
      dominant ALS. In contrast, expression of alsin did not suppress neurotoxicity by
      other neurodegenerative insults such as Alzheimer's disease-related genes.
      Deletion analysis of alsin LF demonstrated that the RhoGEF domain is essential
      for alsin-mediated neuroprotection. Furthermore, we found that alsin LF bound to
      SOD1 mutants, but not to wtSOD1, via the RhoGEF domain. Such functional and
      physical interaction between two ALS-related genes will become a promising clue
      to clarify the pathogenesis of ALS and other motor neuron diseases.

PMID- 14970234
TI  - The Brn-3b transcription factor regulates the growth, behavior, and invasiveness
      of human neuroblastoma cells in vitro and in vivo.
AB  - Neuroblastomas are the second most common solid tumor in children but the
      molecular mechanisms underlying the initiation and progression of this disease
      are poorly understood. We previously showed that the Brn-3b transcription factor
      is highly expressed in actively proliferating neuroblastoma cells but is
      significantly decreased when these cells are induced to differentiate. In this
      study, we analyzed the effects of manipulating Brn-3b levels in the human
      neuroblastoma cell line, IMR-32 and showed that constitutive overexpression of
      Brn-3b consistently increased cellular growth and proliferation in monolayer as
      well as in an anchorage-independent manner compared with controls whereas stably
      decreasing Brn-3b can reduce the rate of growth of these cells. Cells with high
      Brn-3b also fail to respond to growth inhibitory retinoic acid, as they continue
      to proliferate. Moreover, Brn-3b levels significantly modified tumor growth in
      vivo with elevated Brn-3b resulting in faster tumor growth in xenograft models
      whereas decreasing Brn-3b resulted in slower growth compared with controls.
      Interestingly, elevated Brn-3b levels also enhances the invasive capacity of
      these neuroblastoma cells with significantly larger numbers of migrating cells
      observed in overexpressing clones compared with controls. Because invasion and
      metastasis influence morbidity and mortality in neuroblastoma and so
      significantly affect the course and outcome of neuroblastomas, this finding is
      very important. Our results therefore suggest that Brn-3b transcription factor
      contributes to proliferation of neuroblastoma cells in vivo and in vitro but may
      also influence progression and/or invasion during tumorigenesis. It is possible
      that decreasing Brn-3b levels may reverse some effects on growth and
      proliferation of these cells.

PMID- 14970235
TI  - Disruption of the mechanism of long range activation within the human alpha
      globin complex.
AB  - The human alpha-globin complex lies at the tip of the short arm of chromosome 16.
      It comprises three functional globin genes (5'-zeta2-alpha2-alpha1-3'), the
      expression of which is strictly dependent on a positive regulatory element
      located 40-kb upstream, HS-40. This DNase I-hypersensitive site is the only known
      regulatory element displaying strong erythroid-specific enhancer activity within
      the human alpha-globin complex. How this enhancer activity is shared among
      different erythroid genes present in the same cluster without affecting the
      ubiquitous genes present within and around the complex is poorly understood. To
      address this issue, we used hybrid murine erythroleukemia cells containing a
      single copy of human chromosome 16 and targeted the insertion of different
      sequences downstream of HS-40 by recombinase-mediated cassette exchange. We thus
      demonstrate that (i). HS-40-mediated erythroid-specific activation of the alpha
      globin genes is impaired solely by the insertion of a promoter sequence and not a
      coding sequence, unless it is methylated, and that (ii). the degree of
      transcriptional repression observed seems to be related directly to the
      transcriptional rate of the inserted promoter. Taken together, these results
      emphasize the importance of promoter sequences as the main targets for the
      activation mechanism of the human alpha-globin genes by HS-40.

PMID- 14970236
TI  - NF-kappaB site interacts with Sp factors and up-regulates the NR1 promoter during
      neuronal differentiation.
AB  - The NR1 gene undergoes induction in neurogenesis mainly via promoter de
      repression, and up-regulation during neuronal differentiation by undefined
      mechanism(s). Here, we show that in the distal region the NR1 promoter has an
      active NF-kappaB site sharing the consensus with the immunoglobulin (Ig)/human
      immunodeficiency virus NF-kappaB site. Mutation of this site significantly
      reduced NR1 promoter up-regulation during neuronal differentiation of P19 cells.
      Electrophoretic mobility shift assays revealed that P19 nuclei constitutively
      contained p50 and that neuronal differentiation not only increased nuclear p50
      but also induced p65 nuclear translocation. Responding to this change was an up
      regulation of NF-kappaB-dependent promoter activity. However, inhibition of NF
      kappaB nuclear translocation by an IkappaBalpha super-repressor or decoy DNA only
      moderately inhibited NR1 promoter up-regulation. Interestingly, the NR1 NF-kappaB
      site strongly interacted with Sp3/Sp1, instead of NF-kappaB factors, in P19
      nuclear extracts. This interaction was reduced for Sp3 following neuronal
      differentiation, accompanied by dynamic expression of Sp factors. Cotransfection
      of Sp factors (Sp1, 3, or 4) upregulated the NR1 NF-kappaB site dramatically in
      differentiated neurons, but only moderately in undifferentiated P19 cells. This
      up-regulation was strong for Sp1 in differentiated cells and for Sp3 in
      undifferentiated cells. Chromatin-immunoprecipitation assays further demonstrated
      that Sp1 and Sp3 interacted with the NR1 NF-kappaB site in situ, and Sp3 lost its
      interaction after neuronal differentiation. We conclude that the NF-kappaB site
      positively regulates the NR1 promoter during neuronal differentiation via
      interacting mainly with Sp factors and neuronal differentiation reduces the
      effect of Sp3 factor on this site.

PMID- 14970237
TI  - Requirement of the SCFPop1/Pop2 Ubiquitin Ligase for Degradation of the Fission
      Yeast S Phase Cyclin Cig2.
AB  - Two multiprotein E3 (ubiquitin-protein ligase) ubiquitin ligases, the SCF (Skp1
      Cullin-1-F-box) and the APC/C (anaphase promoting complex/cyclosome), are vital
      in ensuring the temporal order of the cell cycle. Particularly, timely
      destruction of cyclins via these two E3s is essential for down-regulation of
      cyclin-dependent kinase. In general, G(1) and S phase cyclins are ubiquitylated
      by the SCF, whereas ubiquitylation of mitotic cyclins is catalyzed by the APC/C.
      Here we show that fission yeast S phase cyclin Cig2 is ubiquitylated and degraded
      via both the SCF and the APC/C. Cig2 instability during G(2) and M phase is
      dependent upon the SCF complex, whereas the APC/C is responsible for Cig2
      destruction during anaphase and G(1), thereby ensuring a spike pattern of Cig2
      levels, peaking only at S phase. Two F-box/WD proteins Pop1 and Pop2, homologues
      of budding yeast Cdc4 and human Fbw7, are responsible for Cig2 instability. Pop1
      binds Cig2 in vivo. An in vitro binding assay shows that an internal 93 amino
      acid residues comprising a part of the cyclin box are necessary and sufficient
      for this binding. Cig2 phosphorylation is also required for interaction with
      Pop1. We previously showed that transcriptional oscillation of cig2(+) requires
      Pop1 and Pop2 function. SCF(Pop1/Pop2) therefore regulates Cig2 levels in a dual
      manner, transcriptionally and post-translationally. Our results also highlight a
      collaborative action of the APC/C and the SCF toward the common substrate Cig2.
      This type of composite degradation control may be more general as the regulatory
      mechanism in other complex systems.

PMID- 14970238
TI  - Actin cytoskeleton is required for nuclear accumulation of Gln3 in response to
      nitrogen limitation but not rapamycin treatment in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae selectively utilizes good nitrogen sources in preference
      to poor ones by down-regulating transcription of genes encoding proteins that
      transport and degrade poor nitrogen sources when excess nitrogen is available.
      This regulation is designated nitrogen catabolite repression (NCR). When cells
      are transferred from a good to a poor nitrogen source (glutamine to proline) or
      treated with rapamycin, an inhibitor of the protein kinases Tor1/2, Gln3 (NCR
      sensitive transcription activator) moves from the cytoplasm into the nucleus.
      Gln3 re-accumulates in the cytoplasm when cells are returned to a good nitrogen
      source. However, Gln3 is not uniformly distributed in the cytoplasm. Such non
      uniform distribution could result from a variety of interactions including
      association with a cytoplasmic vesicular system or components of the
      cytoskeleton. We used latrunculin, a drug that disrupts the actin cytoskeleton by
      inhibiting actin polymerization, to determine whether the actin cytoskeleton
      participates in intracellular Gln3 movement. Latrunculin-treatment prevents
      nuclear accumulation of Gln3 and NCR-sensitive transcription in cells transferred
      from ammonia to proline medium but does not prevent its accumulation in the
      cytoplasm of cells transferred from proline to glutamine medium. In contrast,
      rapamycin-induced nuclear accumulation of Gln3 is not demonstrably affected by
      latrunculin treatment. These data indicate the actin cytoskeleton is required for
      nuclear localization of Gln3 in response to limiting nitrogen but not rapamycin
      treatment. Therefore, the actin cytoskeleton either participates in the response
      of Gln3 intracellular localization to nitrogen limitation before Tor1/2, or
      Tor1/2 inhibition only mimics the outcome of nitrogen limitation rather than
      directly regulating it.

PMID- 14970239
TI  - Cardiac overexpression of myotrophin triggers myocardial hypertrophy and heart
      failure in transgenic mice.
AB  - Cardiac hypertrophy and heart failure remain leading causes of death in the
      United States. Many studies have suggested that, under stress, myocardium
      releases factors triggering protein synthesis and stimulating myocyte growth. We
      identified and cloned myotrophin, a 12-kDa protein from hypertrophied human and
      rat hearts. Myotrophin (whose gene is localized on human chromosome 7q33)
      stimulates myocyte growth and participates in cellular interaction that initiates
      cardiac hypertrophy in vitro. In this report, we present data on the
      pathophysiological significance of myotrophin in vivo, showing the effects of
      overexpression of cardio-specific myotrophin in transgenic mice in which cardiac
      hypertrophy occurred by 4 weeks of age and progressed to heart failure by 9-12
      months. This hypertrophy was associated with increased expression of proto
      oncogenes, hypertrophy marker genes, growth factors, and cytokines, with symptoms
      that mimicked those of human cardiomyopathy, functionally and morphologically.
      This model provided a unique opportunity to analyze gene clusters that are
      differentially up-regulated during initiation of hypertrophy versus transition of
      hypertrophy to heart failure. Importantly, changes in gene expression observed
      during initiation of hypertrophy were significantly different from those seen
      during its transition to heart failure. Our data show that overexpression of
      myotrophin results in initiation of cardiac hypertrophy that progresses to heart
      failure, similar to changes in human heart failure. Knowledge of the changes that
      take place as a result of overexpression of myotrophin at both the cellular and
      molecular levels will suggest novel strategies for treatment to prevent
      hypertrophy and its progression to heart failure.

PMID- 14970240
TI  - Argininosuccinate synthase expression is required to maintain nitric oxide
      production and cell viability in aortic endothelial cells.
AB  - Although cellular levels of arginine greatly exceed the apparent K(m) for
      endothelial nitric-oxide synthase, current evidence suggests that the bulk of
      this arginine may not be available for nitric oxide (NO) production. We propose
      that arginine regeneration, that is the recycling of citrulline back to arginine,
      defines the essential source of arginine for NO production. To support this
      proposal, RNA interference analysis was used to selectively reduce the expression
      of argininosuccinate synthase (AS), because the only known metabolic role for AS
      in endothelial cells is in the regeneration of l-arginine from l-citrulline.
      Western blot analysis demonstrated a significant and dose-dependent reduction of
      AS protein as a result of AS small interfering RNA treatment with a corresponding
      diminished capacity to produce basal or stimulated levels of NO, despite
      saturating levels of arginine in the medium. Unanticipated, however, was the
      finding that the viability of AS small interfering RNA-treated endothelial cells
      was significantly decreased when compared with control cells. Trypan blue
      exclusion analysis suggested that the loss of viability was not because of
      necrosis. Two indicators, reduced expression of Bcl-2 and an increase in caspase
      activity, which correlated directly with reduced expression of AS, suggested that
      the loss of viability was because of apoptosis. The exposure of cells to an NO
      donor prevented apoptosis associated with reduced AS expression. Overall, these
      results demonstrate the essential role of AS for endothelial NO production and
      cell viability.

PMID- 14970241
TI  - Production of melanin by Aspergillus fumigatus.
AB  - Melanins, or melanin-like compounds, may play a role in the pathogenesis of a
      number of human fungal infections. This study investigated the production of
      melanin by the important opportunistic pathogen Aspergillus fumigatus. Conidia
      from A. fumigatus were harvested and treated with proteolytic enzymes, denaturant
      and hot, concentrated acid; this yielded dark particles which were similar in
      size and shape to the original propagules. Electron spin resonance spectroscopy
      revealed that the conidial-derived particles were stable free radicals consistent
      with an identification as melanin. Melanin particles were used to immunize BALB/c
      mice in order to produce a total of five anti-melanin monoclonal antibodies
      (mAbs). The latter mAbs were strongly reactive both with intact conidia and with
      extracted melanin particles by ELISA and immunofluorescence reactivity.
      Immunofluorescence labelling with the novel mAbs was used to examine the temporal
      expression of melanin during in vitro culture of A. fumigatus--melanization was
      confined to conidial structures and was absent from hyphae. SDS-PAGE L-3,4
      dihydroxyphenylalanine (L-DOPA) substrate analysis confirmed the presence of a
      laccase-type activity in conidial extracts, but not in hyphae. Melanin-binding
      mAbs were used to detect the presence of melanized conidia in three patients with
      nasal aspergilloma, indicating that in vivo melanization may occur during
      infection.

PMID- 14970242
TI  - Laboratory diagnosis of legionnaires' disease due to Legionella pneumophila
      serogroup 1: comparison of phenotypic and genotypic methods.
AB  - Laboratory results of 67 cases of legionnaires' disease caused by Legionella
      pneumophila serogroup (Sg) 1 spanning a 6-year period were analysed by both
      phenotypic and genotypic methods. The methods compared were urinary antigen
      enzyme immunoassay (EIA), an immunofluorescent antibody (IFA) test, direct
      fluorescent antibody (DFA), culture and a 5S rRNA PCR with Southern blotting
      confirmation. Urine was available in 53 cases, of which 35 (66%) were positive,
      with an antigen peak observed at 5-10 days after onset of disease symptoms. The
      IFA test was positive in 62 (92.5%) cases, with 56 (90.3%) cases producing a
      greater than fourfold rise in titre and 6 (9.7%) giving presumptive high titres
      of > or =1:128. There were two antibody peaks, one at 10-15 days and another at
      >25 days after onset. In 23 cases where samples were available, DFA and culture
      were respectively positive in 5 (22%) and 10 (48%) cases. There was a peak in
      culture-positives 5-10 days after onset of disease. A Legionella-specific 5S rRNA
      PCR on patient serum was positive in 54 (80.5%) cases, with a peak in PCR
      positivity at 6-10 days after disease onset. In 22 of the 67 cases, the full
      panel of diagnostic methods was available for comparison. The relative
      sensitivity and specificity of the urinary antigen EIA and the serum PCR was
      100%. The IFA gave relative sensitivity and specificity values of 93.8 and 95%.
      DFA and culture, although 100% specific, produced only low sensitivities, of 19
      and 42.8%, respectively. This study has shown that urinary antigen and serum PCR
      are valuable tests in the acute phase of disease, with excellent sensitivity and
      specificity values. At present, the Legionella species causing infection requires
      to be verified by IFA serology and/or culture, but this could become unnecessary
      as new antigen and L. pneumophila Sg 1-specific PCR tests become available.

PMID- 14970243
TI  - Autolysin-targeted LightCycler assay including internal process control for
      detection of Streptococcus pneumoniae DNA in clinical samples.
AB  - The development and clinical evaluation of a LightCycler PCR assay, including an
      internal process control (IPC), to detect the Streptococcus pneumoniae autolysin
      gene in clinical samples is reported. The assay was developed to provide a second
      target for use in conjunction with existing pneumolysin PCR assays to increase
      the reliability of non-culture PCR diagnosis of pneumococcal infection. Primers
      amplify a 173 bp fragment of the autolysin gene (lytA), which is detected by
      fluorescence-labelled hybridization probes. An IPC was designed to check for the
      presence of PCR inhibitors and loss of assay sensitivity. The IPC product was
      amplified by the lytA primers and detected by a second set of hybridization
      probes. The analytical specificity of the autolysin PCR assay was 100% against 39
      other bacterial species tested; these included related streptococci and other
      organisms. The assay, which could reliably detect 50 fg purified pneumococcal DNA
      per reaction, was capable of distinguishing between S. pneumoniae and atypical
      Streptococcus mitis and Streptococcus oralis strains known to contain the lytA
      gene. Using DNA extracts from a panel of EDTA bloods from patients with blood
      culture-confirmed pneumococcal infection, the autolysin PCR had a sensitivity of
      42.9%, which was similar to a previously reported TaqMan pneumolysin PCR (43.8%)
      run in parallel. Total agreement was shown between the autolysin assay and the
      pneumolysin TaqMan assay when used to test 23 culture-negative clinical samples,
      of which eight were positive by PCR, adding valuable clinical information. A
      specific autolysin-based LightCycler assay has been developed to complement
      pneumolysin PCR for the detection of S. pneumoniae in clinical samples. This
      should be a particularly useful tool for the rapid and sensitive diagnosis of
      pneumococcal meningitis, even after an antibiotic has been administered. However,
      poor sensitivity on blood samples limits its usefulness in other bacteraemic
      infections.

PMID- 14970244
TI  - Immunological detection and cytotoxic properties of toxins from toxin A-positive,
      toxin B-positive Clostridium difficile variants.
AB  - Clostridium difficile is a major nosocomial pathogen and a causative agent of
      antibiotic-associated diarrhoea and pseudomembranous colitis. PCR analysis of the
      toxin A and B genes of this bacterium has revealed 20 variant types (toxinotypes
      I-XX), many of which can cause human disease. Strains comprising the 15 toxin A
      positive, toxin B-positive toxinotypes are not usually differentiated from non
      variant strains by routine laboratories that do not utilize PCR tests.
      Consequently, the toxins from these variant strains have not been investigated
      thoroughly. The present studies revealed that toxin A-positive (A+B+) strains
      representing 12 variant toxinotypes all express considerably lower levels of
      toxin A and are less cytotoxic in vitro than non-variant strain VPI 10463.
      Truncated forms of toxin A were detected by immunoblotting in toxinotype VI and
      VII strains and these toxins were differentiated from each other and from toxin A
      of the non-variant strain. A further novel finding was the ability of toxin A
      positive (A+B+) strains of toxinotypes IX, XIV and XV to exhibit an alternative
      Clostridium sordellii-like cytopathic effect on Vero cells, characterized by
      marked cell clumping. A rapid and simple method for toxin A removal from culture
      filtrates was developed. This enabled confirmation that the abnormal cytotoxicity
      observed for these strains is due to an altered toxin B, as has been found in
      toxin A-negative (A-B+) strains. These findings indicate the potential for
      differentiation of certain toxin A-positive (A+B+) toxinotypes without the need
      for PCR techniques.

PMID- 14970245
TI  - Characterization of elongated Helicobacter pylori isolated from a patient with
      gastric-mucosa-associated lymphoid-tissue lymphoma.
AB  - To date, two Helicobacter species, Helicobacter pylori and 'Helicobacter
      heilmannii' (formerly named 'Gastrospirillum hominis'), have been identified from
      the human stomach. In this study, we observed non-H. pylori-shaped bacteria in
      gastric tissue sections and successfully isolated them by cultivation. Elongated
      bacteria were isolated from a patient with gastric-mucosa-associated lymphoid
      tissue lymphoma who had been diagnosed as H. pylori-negative by culture, rapid
      urease test and histopathology in another hospital. The bacteria were grown only
      on chocolate agar in a CO2 incubator, appeared more than 10 microm long in
      histological sections, formed small colonies and showed poor growth in a brain
      heart infusion broth; these characteristics apparently differed from common
      clinical isolates of H. pylori. However, the bacteria were identified as H.
      pylori by PCR of the urease gene, 16S rDNA sequencing, protein profile and
      antigenicity examined by anti-H. pylori polyclonal antibody. These observations
      suggest that the H. pylori strain identified in this study may contribute to the
      development of gastroduodenal diseases in cases judged as H. pylori-negative by
      ordinary methods.

PMID- 14970246
TI  - Relationship between penicillin-binding protein patterns and beta-lactamases in
      clinical isolates of Bacteroides fragilis with different susceptibility to beta
      lactam antibiotics.
AB  - This study examines the role of the penicillin-binding proteins (PBPs) of
      Bacteroides fragilis in the mechanism of resistance to different beta-lactam
      antibiotics. Six of the eight strains used were beta-lactamase-positive by the
      nitrocefin assay. These strains displayed reduced susceptibility to imipenem
      (MIC, 2-16 mg l(-1)) and some of them were resistant to the actions of
      ampicillin, cefuroxime, cephalexin, cefoxitin and piperacillin. When studying
      specific enzymic activity, the capacity to degrade cefuroxime was only detected
      in strains AK-4, R212 and 0423 and the capacity to degrade cephalexin was only
      detected in strains R212 and 2013E; no specific activity was detected on
      imipenem. Metallo-beta-lactamase activity was only detected in strains AK-2 and
      119, despite the fact that the cfiA gene was identified in four strains (AK-2,
      2013E, 119 and 7160). The cepA gene was detected in six of the eight strains
      studied. Three high-molecular-mass PBPs were detected in all strains; however, in
      some cases, PBP2Bfr and/or PBP3Bfr appeared as a faint band. PBP4Bfr and PBP5Bfr
      were detected in six strains. PBP6Bfr only was detected in B. fragilis strains AK
      2, 0423, 119 and 7160. By analysis of the sequence of B. fragilis chromosomal DNA
      and comparison with genes that are known to encode PBPs in Escherichia coli, six
      genes that encode PBP-like proteins were detected in the former organism. The
      gene that encodes the PBP2 orthologue of E. coli (pbpABfr, PBP3Bfr) was sequenced
      in six of the eight strains and its implications for resistance were examined.
      Differences in the PBP3Bfr amino acid sequences of strains AK-2 and 119 and their
      production of beta-lactamases indicate that these differences are not involved in
      the mechanism of resistance to imipenem and/or cephalexin.

PMID- 14970247
TI  - Genetic analysis of Staphylococcus aureus from intravenous drug user lesions.
AB  - Multilocus sequence typing (MLST) of 48 methicillin-sensitive Staphylococcus
      aureus isolates from intravenous drug user abscesses/soft-tissue infections
      revealed 12 sequence types (STs) belonging to eight genetically distinct
      lineages. Only two novel STs were recovered (one isolate of each), indicating
      that isolates in this study were similar to those from previous studies of
      disease and carriage. However, ST59, the most common genotype recovered (from six
      individuals), may be adept at causing subcutaneous lesions in this patient
      population, as it is rare in carriage and disease. PCR detection of 22 toxin
      genes revealed a high prevalence of the gene for staphylococcal enterotoxin B
      compared with previous studies, indicating that this toxin may promote infections
      in this patient group.

PMID- 14970248
TI  - Biotypes of group A streptococci isolated from children.
AB  - Thirty-eight isolates of group A streptococci from patients with pharyngitis, 13
      isolates from patients with pyoderma and 28 carrier strains were subjected to
      biotyping by carbohydrate fermentation tests and production of beta
      glucuronidase. Biotype 10 was observed most frequently among clinical isolates
      and biotypes 3 and 4 were most common among carrier isolates.

PMID- 14970249
TI  - cagA genotype and variants in Chinese Helicobacter pylori strains and
      relationship to gastroduodenal diseases.
AB  - Previous studies have implicated CagA [encoded by cytotoxin-associated gene A
      (cagA)] in Helicobacter pylori-associated gastroduodenal pathology and distinct
      subgenotypes of cagA may circulate in different pathological manifestations of
      cagA-positive H. pylori infection. To investigate cagA genotype and variants in
      Chinese H. pylori strains and explore their relationship with gastroduodenal
      diseases, the cagA status of 82 Chinese H. pylori strains was examined and
      variation in size of the 3' region of cagA in 71 of these strains was analysed by
      PCR. cagA was detected in 28 (100%) of 28 strains from peptic ulcer patients, two
      (100%) of two strains from gastric cancer patients, 32 (94.1%) of 34 strains from
      chronic gastritis patients and 17 (94.4%) of 18 strains from healthy volunteers.
      PCR products of the cagA 3' variable region were obtained from 71 (92.2%) of 77
      Chinese H. pylori strains and could be classified into subgenotypes I, II and
      III, which gave PCR products of around 825, 900 and 950 bp, respectively.
      Subgenotype I cagA predominated in Chinese H. pylori strains (67/71), whereas
      subgenotype II cagA presented in two isolates from patients with chronic
      gastritis and subgenotype III presented in two isolates from healthy volunteers.
      Therefore, neither cagA nor its 3' region variants can be used as a sole marker
      for the presence of particular H. pylori-related gastroduodenal diseases in the
      Chinese population.

PMID- 14970250
TI  - Prevalence of childhood diarrhoea-associated Escherichia coli in Thailand.
AB  - Escherichia coli isolates (n=2629) were collected between 1996 and 2000 from 2100
      Thai children less than 12 years of age with acute diarrhoea. Enterotoxigenic
      (ETEC), enteroinvasive (EIEC), Shiga-toxin-producing (STEC), enteropathogenic
      (EPEC) and enteroaggregative (EAEC) E. coli were identified by their virulence
      marker profiles, as determined by multiplex PCR, and HeLa cell-adherence
      patterns. Serogroups of isolates were determined using 43 monovalent O antisera.
      Of 2629 isolates, 16.9% were identified as diarrhoeagenic E. coli, and the mean
      isolation rates per year were 10.2% for EAEC (range 8-12.5%), 3.2% for EPEC (0
      8%), 3.0% for ETEC (2-5.4%), 0.5% for EIEC (0-1%) and 0.04 % for STEC (0-0.1%).
      The isolation rates of pathotypes from four different age groups (0-5 months, 6
      11 months, 1-2 years and 2-12 years) in 905 children whose ages were recorded
      were respectively 19.3, 18.2, 9.1 and 8.1% for EAEC, 3.1, 4.3, 1.7 and 2.2% for
      EPEC and 2.6, 2.3, 1.3 and 5% for ETEC. About 38% of diarrhoeagenic E. coli,
      including 55.1, 66.7, 100, 45.9 and 29%, respectively, of ETEC, EIEC, STEC, EPEC
      and EAEC, and 24% of non-diarrhoeagenic E. coli were O-antigen typable. Only four
      serogroups (9.3%) were restricted to single pathotypes, whereas 27 serogroups
      (62.8%) were not restricted to any pathotype. This study shows that EAEC are the
      most prevalent diarrhoea-associated pathotype in Thai children.

PMID- 14970251
TI  - Capnocytophaga canimorsus endocarditis.
AB  - Capnocytophaga canimorsus is a fastidious, Gram-negative rod that forms part of
      the normal oral flora of dogs and cats. Known for its ability to cause fulminant
      sepsis following dog bites, particularly in asplenic patients or alcoholics, this
      bacterium is also an uncommon cause of endocarditis. This article reviews 12
      cases of endocarditis caused by C. canimorsus. Mean age of patients was 53 years,
      with 78% of cases occurring in males. Overall, a history of dog-bite was
      documented in four cases (33%) and a further four (33%) reported contact with
      dogs. Four (33%) of the endocarditis cases had underlying cardiological risk
      factors and two abused alcohol, but none had had a previous splenectomy. Subacute
      presentation, often involving more than one hospital admission, was common, as
      were initially negative blood cultures. A variety of antibiotics was used, but
      penicillins were the most common therapy. Three (25%) of the 12 endocarditis
      patients died.

PMID- 14970252
TI  - Colonization of the neonatal rat intestinal tract from environmental exposure to
      the anaerobic bacterium Oxalobacter formigenes.
AB  - Oxalobacter formigenes, an anaerobic bacterium that inhabits the mammalian
      gastrointestinal tract, has an important symbiotic relationship with its
      vertebrate hosts by regulating oxalic acid homeostasis. Epidemiological studies
      of O. formigenes colonization in man have shown that colonization occurs in young
      children, that every child can become colonized naturally, that >20% lose
      colonization during adolescence or as adults and that stable colonization can be
      disrupted by antibiotic use or changes in diet, greatly affecting subsequent
      health. As O. formigenes is a fastidious anaerobe that seldom re-colonizes
      adults, the question arises as to how initial colonization occurs. To investigate
      this question, non-colonized female laboratory rats were placed on diets high in
      oxalate and were colonized by oesophageal gavage with O. formigenes either before
      or after being impregnated. Faecal specimens from their offspring were tested for
      the presence of O. formigenes. Although the bacterium was first detected in a few
      neonates as early as 7 days post-partum, colonization of all the offspring did
      not occur until after weaning. In each case, the offspring were colonized with
      the bacterial strain carried by their mothers. To determine whether O. formigenes
      colonization occurs vertically or horizontally, newborn rats were placed with
      foster mothers that were either non-colonized or colonized with an O. formigenes
      strain different from that of their natural mothers. Colonization occurred
      temporally in a manner similar to natural colonization but all offspring became
      colonized only with the O. formigenes strain of the foster mothers. These data
      indicate that intestinal colonization occurs horizontally, but does not answer
      the question of how O. formigenes survives the aerobic environment in order to be
      transmitted.

PMID- 14970253
TI  - Cyclosporiasis associated with diarrhoea in an immunocompetent patient in Turkey.
AB  - Cyclospora cayetanensis, the parasitic agent responsible for human
      cyclosporiasis, is an emerging worldwide cause of diarrhoea in immunocompetent
      people as well as in immunocompromised patients, such as those with AIDS.
      Reported here is the case of a 30-year-old Turkish woman, a lawyer, who was
      admitted to hospital in July 2002 with complaints of watery diarrhoea, anorexia,
      nausea, vomiting, abdominal pain and weight loss over a period of 1 week.
      Cyclospora sp. oocysts were determined by using modified Kinyoun's acid-fast
      stain. The patient was treated with trimethoprim/sulfamethoxazole (160/800 mg)
      b.i.d. for 7 days. This report is the first example of autochthonous
      cyclosporiasis in an immunocompetent patient in Turkey.

PMID- 14970254
TI  - Enterococcus durans endocarditis in a patient with transposition of the great
      vessels.
AB  - A case of native valve endocarditis caused by Enterococcus durans in a patient
      with transposition of the great vessels is reported. The patient was treated
      initially with gentamicin and ceftriaxone; after isolation of enterococci,
      ceftriaxone was switched to ampicillin. The only virulence factors established in
      the strain were haemolytic activity and biofilm formation.

PMID- 14970255
TI  - Preconditioning-induced cytoprotection in hepatocytes requires Ca(2+)-dependent
      exocytosis of lysosomes.
AB  - A short period of hypoxia reduces the cytotoxicity produced by a subsequent
      prolonged hypoxia in isolated hepatocytes. This phenomenon, termed hypoxic
      preconditioning, is mediated by the activation of adenosine A2A-receptor and is
      associated with the attenuation of cellular acidosis and Na+ overload normally
      occurring during hypoxia. Bafilomycin, an inhibitor of the vacuolar H+/ATPase,
      reverts the latter effects and abrogates the preconditioning-induced
      cytoprotection. Here we provide evidence that the acquisition of preconditioning
      induced cytoprotection requires the fusion with plasma membrane and exocytosis of
      endosomal-lysosomal organelles. Poisons of the vesicular traffic, such as
      wortmannin and 3-methyladenine, which inhibit phosphatydilinositol 3-kinase, or
      cytochalasin D, which disassembles the actin cytoskeleton, prevented lysosome
      exocytosis and also abolished the preconditioning-associated protection from
      acidosis and necrosis provoked by hypoxia. Preconditioning was associated with
      the phosphatydilinositol 3-kinase-dependent increase of cytosolic [Ca2+].
      Chelation of free cytosolic Ca2+ in preconditioned cells prevented lysosome
      exocytosis and the acquisition of cytoprotection. We conclude that lysosome
      plasma membrane fusion is the mechanism through which hypoxic preconditioning
      allows hepatocytes to preserve the intracellular pH and survive hypoxic stress.
      This process is under the control of phosphatydilinositol 3-kinase and requires
      the integrity of the cytoskeleton and the rise of intracellular free calcium
      ions.

PMID- 14970256
TI  - Epidermal cells accelerate the restoration of the blood flow in diabetic ischemic
      limbs.
AB  - Epidermal progenitor cells (EpPCs) were long thought to be unipotent, giving rise
      only to other keratinocytes but recent studies question this assumption. Here, we
      investigated whether mouse EpPCs can adopt other antigenic and functional
      phenotypes. To test this, we injected freshly isolated and cultured EpPCs and
      transient amplifying cells into diabetic and non-diabetic mouse ischemic hindlimb
      and followed the cells' fate and the recovery of the ischemic limb blood flow
      over time. Both freshly isolated and cultured EpPCs and transient amplifying
      cells were incorporated into the vasculature of the ischemic limb 2 and 5 weeks
      post-injection, and some expressed endothelial cell but not keratinocyte
      antigens. Additionally, in the non-diabetic animals, first transient amplifying
      cells and then EpPCs accelerated the restoration of the blood flow. By contrast,
      in diabetic animals, only injected EpPCs or unsorted epidermal cells accelerated
      the restoration of the blood flow. These data indicate that epidermal cells can
      adopt non-skin phenotypes and functions, and that this apparent pluripotency is
      not lost by differentiation of EpPCs into transient amplifying cells. They also
      suggest that epidermal cell therapy might be of therapeutic value in the
      treatment of diabetic ischemia. Finally, because epidermal cells are readily
      accessible and expandable, they appear to be ideally suited for use as a non
      viral gene delivery therapy.

PMID- 14970258
TI  - The cytoplasmic domain of CEACAM1-L controls its lateral localization and the
      organization of desmosomes in polarized epithelial cells.
AB  - Two CEACAM1 isoforms with different cytoplasmic domains, CEACAM1-L and CEACAM1-S,
      are unequally distributed in polarized epithelial MDCK cells. CEACAM1-S is
      exclusively apical whereas CEACAM1-L occurs both in apical and lateral cell
      surfaces. Using confocal microscopy and CEACAM1-L mutants, we identified several
      amino acids in the cytoplasmic domain that were instrumental for the lateral
      localization. Tyr515, but not Tyr488, constituted a prominent lateral targeting
      signal. Pervanadate-stimulated Tyr phosphorylation induced rapid
      phosphatidylinositol 3-kinase-dependent disappearance of lateral CEACAM1-L,
      whereas staurosporine, a Ser/Thr kinase inhibitor, resulted in slower
      phosphatidylinositol 3-kinase-independent disappearance. Both drugs caused
      accumulation of CEACAM1-L in a late endosome/lysosome compartment. Colocalization
      studies of occludin, ZO-1, E-cadherin, beta-catenin and desmoplakin indicated
      that laterally localized CEACAM1-L was present in adherens junctions but not in
      tight junctions or desmosomes. Overexpressed CEACAM1-L did not affect the
      organization of tight junction or adherens junction proteins, but perturbed the
      arrangement of desmosomes. The abundance of desmosomes in the lateral cell
      surfaces decreased significantly and the submembraneous cytokeratin filaments
      became disorganized. The signal for desmosomal perturbance resided within amino
      acids 484-518 in the C-terminal part of the cytoplasmic domain, among which an
      intact Tyr515 was indispensable.

PMID- 14970257
TI  - Adenomatous polyposis coli and EB1 localize in close proximity of the mother
      centriole and EB1 is a functional component of centrosomes.
AB  - Adenomatous polyposis coli (APC) and End-binding protein 1 (EB1) localize to
      centrosomes independently of cytoplasmic microtubules (MTs) and purify with
      centrosomes from mammalian cell lines. Localization of EB1 to centrosomes is
      independent of its MT binding domain and is mediated by its C-terminus. Both APC
      and EB1 preferentially localize to the mother centriole and EB1 forms a cap at
      the end of the mother centriole that contains the subdistal appendages as defined
      by epsilon-tubulin localization. Like endogenous APC and EB1, fluorescent protein
      fusions of APC and EB1 localize preferentially to the mother centriole. Depletion
      of EB1 by RNA interference reduces MT minus-end anchoring at centrosomes and
      delays MT regrowth from centrosomes. In summary, our data indicate that APC and
      EB1 are functional components of mammalian centrosomes and that EB1 is important
      for anchoring cytoplasmic MT minus ends to the subdistal appendages of the mother
      centriole.

PMID- 14970259
TI  - Involvement of the cohesin Rad21 and SCP3 in monopolar attachment of sister
      kinetochores during mouse meiosis I.
AB  - SCP3 is a meiosis-specific structural protein appearing at axial elements and
      lateral elements of the synaptonemal complex. We have analysed the behaviour of
      SCP3 and the cohesin subunit Rad21 in mouse spermatocytes by means of a squashing
      technique. Our results demonstrate that both proteins colocalize and are
      partially released from chromosome arms during late prophase I stages, although
      they persist at the interchromatid domain of metaphase I bivalents. Thus, Rad21
      cannot be considered a 'mitotic'-specific variant, but coexists with Rec8. During
      late prophase I SCP3 and Rad21 accumulate at centromeres, and together with the
      chromosomal passenger proteins INCENP and aurora-B kinase, show a complex 'double
      cornet'-like distribution at the inner domain of metaphase I centromeres beneath
      the associated sister kinetochores. We have observed that Rad21 and SCP3 are
      displaced from centromeres during telophase I when sister kinetochores separate,
      and are not present at metaphase II centromeres. Thus, we hypothesise that Rad21,
      and the superimposed SCP3 and SCP2, are involved in the monopolar attachment of
      sister kinetochores during meiosis I, and are not responsible for the maintenance
      of sister-chromatid centromere cohesion during meiosis II as previously
      suggested.

PMID- 14970260
TI  - The 12 kDa FK506-binding protein, FKBP12, modulates the Ca(2+)-flux properties of
      the type-3 ryanodine receptor.
AB  - We have characterised the functional regulation of the type-3 ryanodine receptor
      by the 12 kDa FK506-binding protein. Wild-type type-3 ryanodine receptor and
      mutant type-3 ryanodine receptor in which the critical valine at position 2322 in
      the central 12 kDa FK506-binding protein binding site was substituted by
      aspartate, were stably expressed in human embryonic kidney cells. In contrast to
      the wild-type receptor, the mutant receptor was strongly impaired in binding to
      immobilised glutathione S-transferase 12 kDa FK506-binding protein. Caffeine
      induced 45Ca(2+)-efflux was markedly increased in cells expressing mutant type-3
      ryanodine receptor whereas the maximal-releasable Ca2+ was not affected. Confocal
      Ca2+ imaging provided clear evidence for a much higher sensitivity of the mutant
      receptor, which showed global Ca2+ release at about 20-fold lower caffeine
      concentrations than the wild-type receptor. Spontaneous Ca2+ sparks were observed
      in both wild-type- and mutant-expressing cells but the number of sparking cells
      was about 1.5-fold higher in the mutant group, suggesting that the degree of
      FK506 binding controls the stability of the closed state of ryanodine receptor
      channels. Furthermore, overexpression of 12 kDa FK506-binding protein decreased
      the number of sparking cells in the wild-type-expressing cells whereas it did not
      affect the number of sparking cells in cells expressing the mutant receptor.
      Concerning spark properties, the amplitude and duration of Ca2+ sparks mediated
      by mutant channels were significantly reduced in comparison to wild-type
      channels. This suggests that functional coupling between different mutant type-3
      ryanodine receptor channels in a cluster is impaired. Our findings show for the
      first time that the central binding site for the 12 kDa FK506-binding protein of
      type-3 ryanodine receptor, encompassing the critical valine proline motif, plays
      a crucial role in the modulation of the Ca2+ release properties of the type-3
      ryanodine receptor channel, including the regulation of both global Ca2+
      responses and spontaneous Ca2+ sparks.

PMID- 14970261
TI  - Microtubule motors control membrane dynamics of Salmonella-containing vacuoles.
AB  - Infection of host cells by Salmonella enterica serovar Typhimurium (S.
      typhimurium) leads to the formation of specialised membrane-bound compartments
      called Salmonella-containing vacuoles (SCVs). Bacteria remain enclosed by the
      vacuolar membrane as they divide, and by translocating effector proteins across
      the vacuolar membrane through the SPI-2 type III secretion system, they interfere
      with host cell processes in ways that promote bacterial growth. One such effector
      is SifA, which is required to maintain the integrity of the vacuolar membrane and
      for the formation in epithelial cells of long tubular structures called Sifs that
      are connected to SCVs. Unknown effector(s) mediate the assembly of a meshwork of
      F-actin around SCVs. We report that intracellular bacteria also cause a dramatic
      accumulation of microtubules around S. typhimurium microcolonies in both
      epithelial cells and macrophages. Although this process appears to be independent
      of SPI-2-mediated F-actin assembly, it does require bacterial protein synthesis.
      In epithelial cells, microtubule accumulation is accompanied by the recruitment
      of both kinesin and dynein. Inhibition of the activity of either motor prevented
      both Sif formation and the loss of vacuolar membrane from sifA mutant bacteria.
      It also resulted in morphologically abnormal vacuoles enclosing wild-type
      bacteria, and impaired their replication. Our experiments indicate that
      recruitment of dynein to SCVs is dependent on Rab7 activity. We show that the
      recently described Rab7 effector RILP is also recruited to SCVs in a Rab7
      dependent manner. However, overexpression of RILP did not restore dynein
      recruitment to SCVs in cells expressing dominant negative Rab7, suggesting that
      RILP requires a functional Rab7 to be activated at the SCV membrane, or that
      dynein recruitment is mediated by an effector other than RILP. Together, these
      experiments indicate that microtubule motors play important roles in regulating
      vacuolar membrane dynamics during intracellular replication of S. typhimurium.

PMID- 14970262
TI  - Caspase-mediated cleavage of syntaxin 5 and giantin accompanies inhibition of
      secretory traffic during apoptosis.
AB  - We report the caspase-dependent cleavage of two Golgi-associated transport
      factors during apoptosis. The tethering factor giantin is rapidly cleaved both in
      vitro and in vivo at a conserved site, to generate a stable membrane-anchored
      domain and a soluble domain that is subject to further caspase-dependent
      cleavage. The t-SNARE syntaxin 5 is also cleaved rapidly, resulting in the
      separation of the catalytic membrane-proximal domain from an N-terminal
      regulatory domain. Cleavage of giantin and syntaxin 5 is accompanied by a
      cessation of vesicular transport between the ER and the Golgi complex, which
      first manifests itself as a block in ER exit. The contribution that such an
      inhibition of trafficking may make towards the generation of an apoptotic
      phenotype is discussed.

PMID- 14970263
TI  - Epidermal growth factor regulates ubiquitination, internalization and proteasome
      dependent degradation of connexin43.
AB  - Connexins are membrane-spanning proteins that form gap junction channels between
      adjacent cells. Connexin43 (Cx43), the most widely expressed member of the
      connexin family in tissues and cell lines, has a rapid turnover rate and its
      degradation involves both the lysosomal and ubiquitin-proteasome pathway. It was
      previously shown that the proteasome is involved in regulating the number of
      functional gap junctions at the plasma membrane. However, little is known about
      how proteasome-dependent turnover of Cx43 is controlled. Epidermal growth factor
      (EGF) induces hyperphosphorylation of Cx43 and a rapid, transient decrease in gap
      junctional intercellular communication. In this study, we show that, along with
      inhibition of gap junctional intercellular communication, EGF induces
      disorganization, internalization and degradation of Cx43 gap junction plaques in
      IAR20 rat liver epithelial cells. These EGF-induced modifications of Cx43 were
      counteracted by the MEK1 inhibitor PD98059, indicating that the effects were
      mediated by the mitogen-activated protein kinase pathway. The EGF-induced
      destruction of Cx43 was proteasome-dependent, because the loss of Cx43 protein
      was counteracted by the proteasome inhibitor MG132 but not the lysosomal
      inhibitor leupeptin. Furthermore, EGF induced ubiquitination of Cx43, which was
      associated with the Cx43 hyperphosphorylation. The EGF-induced Cx43
      ubiquitination was counteracted by PD98059. The EGF-induced internalization of
      Cx43 was blocked by hypertonic sucrose treatment, indicating that EGF mediates
      internalization of Cx43 via a clathrin-dependent mechanism. Our results indicate
      that ubiquitination of Cx43 occurs at the plasma membrane before Cx43
      internalization. Taken together, these data provide the first evidence that EGF
      induced phosphorylation of Cx43 induces binding of ubiquitin and targets Cx43 for
      internalization and degradation in a proteasome-dependent manner.

PMID- 14970264
TI  - The bHLH TAL-1/SCL regulates endothelial cell migration and morphogenesis.
AB  - The basic helix-loop-helix tal-1 gene (or scl), known for its fundamental role in
      embryonic and adult hematopoiesis in vertebrates, is also required for embryonic
      vascular remodeling. In adults, TAL-1 protein is undetectable in quiescent
      endothelium but it is present in newly formed vessels including tumoral
      vasculature, indicating its involvement in angiogenesis. Here, we demonstrate
      that TAL-1 expression is tightly regulated during in vitro angiogenesis: it is
      low during the initial step of migration and is upregulated during formation of
      capillary-like structures. We investigated whether ectopic expression of either
      wild-type TAL-1 or a dominant-negative mutant lacking the DNA-binding domain
      (Delta-bas) modulates the activity of human primary endothelial cells in the
      angiogenic processes of migration, proliferation and cell morphogenesis.
      Overexpression of either wild-type or Delta-bas TAL-1 affected chemotactic
      migration of primary endothelial cells without modifying their proliferative
      properties. Ectopic expression of wild-type TAL-1 accelerated the formation of
      capillary-like structures in vitro and, in vivo, enhanced vascularisation in mice
      (Matrigel implants) associated with a general enlargement of capillary lumens.
      Importantly, transduction of the mutant Delta-bas completely impaired in vitro
      angiogenesis and strongly inhibited vascularisation in mice. Taken together, our
      data show that TAL-1 modulates the angiogenic response of endothelial cells by
      stimulating cell morphogenesis and by influencing their behavior in migration.
      This study highlights the importance of TAL-1 regulation in postnatal vascular
      remodeling and provides the first physiological evidence that links TAL-1
      activity to endothelial cell morphogenic processes.

PMID- 14970265
TI  - Tissue microarrays for hypothesis generation.

PMID- 14970266
TI  - Have we resolved how to triage equivocal cervical cytology?

PMID- 14970267
TI  - Aspirin for cancer chemoprevention: still a headache?

PMID- 14970269
TI  - Norwegian law brings alternative medicine to the mainstream.

PMID- 14970270
TI  - Stat bite: Estimated deaths from selected cancers in the United States, 2004.

PMID- 14970271
TI  - Connecting viruses to cancer: how research moves from association to causation.

PMID- 14970272
TI  - Accidental passengers or perpetrators? Current virus-cancer research.

PMID- 14970273
TI  - IOM report targets testosterone therapy.

PMID- 14970275
TI  - Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch
      syndrome) and microsatellite instability.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome,
      is a common autosomal dominant syndrome characterized by early age at onset,
      neoplastic lesions, and microsatellite instability (MSI). Because cancers with
      MSI account for approximately 15% of all colorectal cancers and because of the
      need for a better understanding of the clinical and histologic manifestations of
      HNPCC, the National Cancer Institute hosted an international workshop on HNPCC in
      1996, which led to the development of the Bethesda Guidelines for the
      identification of individuals with HNPCC who should be tested for MSI. To
      consider revision and improvement of the Bethesda Guidelines, another HNPCC
      workshop was held at the National Cancer Institute in Bethesda, MD, in 2002. In
      this commentary, we summarize the Workshop presentations on HNPCC and MSI
      testing; present the issues relating to the performance, sensitivity, and
      specificity of the Bethesda Guidelines; outline the revised Bethesda Guidelines
      for identifying individuals at risk for HNPCC; and recommend criteria for MSI
      testing.

PMID- 14970276
TI  - Loss of the tumor suppressor PML in human cancers of multiple histologic origins.
AB  - BACKGROUND: The PML gene is fused to the RARalpha gene in the vast majority of
      acute promyelocytic leukemias (APL) and has been implicated in the control of key
      tumor-suppressive pathways. However, its role in the pathogenesis of human
      cancers other than APL is still unclear. We therefore assessed the status and
      expression of the PML gene in solid tumors of multiple histologic origins.
      METHODS: We created tumor tissue microarrays (TTMs) with samples from patients
      with colon adenocarcinoma (n = 109), lung carcinoma (n = 19), prostate
      adenocarcinoma (n = 36), breast carcinoma (n = 38), central nervous system (CNS)
      tumors (n = 51), germ cell tumors (n = 60), thyroid carcinoma (n = 32), adrenal
      cortical carcinoma (n = 12), and non-Hodgkin's lymphoma (n = 251) and from normal
      tissue corresponding to each histotype and analyzed PML protein and mRNA
      expression by immunohistochemistry and in situ hybridization, respectively. Tumor
      cell lines (n = 64) of various histologic origins were analyzed for PML protein
      and mRNA expression by immunofluorescence and northern blotting, respectively.
      DNA from microdissected tumor samples and cell lines was analyzed for PML
      mutations and loss of heterozygosity (LOH). For some tumor types, the association
      between PML expression and tumor stage and grade was analyzed. Statistical tests
      were two-sided. RESULTS: All normal tissues expressed PML protein. PML protein
      expression was reduced or abolished in prostate adenocarcinomas (63% [95%
      confidence interval [CI] = 48% to 78%] and 28% [95% CI = 13% to 43%],
      respectively), colon adenocarcinomas (31% [95% CI = 22% to 40%] and 17% [95% CI =
      10% to 24%]), breast carcinomas (21% [95% CI = 8% to 34%] and 31% [95% CI = 16%
      to 46%]), lung carcinomas (36% [95% CI = 15% to 57%] and 21% [95% = 3% to 39%]),
      lymphomas (14% [95% CI = 10% to 18%] and 69% [95% CI = 63% to 75%]), CNS tumors
      (24% [95% CI = 13% to 35%] and 49% [95% CI = 36% to 62%]), and germ cell tumors
      (36% [95% CI = 24% to 48%] and 48% [95% CI = 36% to 60%]) but not in thyroid or
      adrenal carcinomas. Loss of PML protein expression was associated with tumor
      progression in prostate cancer (the progression from prostatic intraepithelial
      neoplasia to invasive carcinoma was associated with complete PML loss; P<.001),
      breast cancer (complete PML loss was associated with lymph node metastasis; P
      =.01), and CNS tumors (complete PML loss was associated with high-grade tumors; P
      =.003). PML mRNA was expressed in all tumor and cell line samples. The PML gene
      was rarely mutated and was not subject to LOH. CONCLUSIONS: PML protein
      expression is frequently lost in human cancers of various histologic origins, and
      its loss associates with tumor grade and progression in some tumor histotypes.

PMID- 14970277
TI  - Virologic versus cytologic triage of women with equivocal Pap smears: a meta
      analysis of the accuracy to detect high-grade intraepithelial neoplasia.
AB  - BACKGROUND: The appropriate management of women with minor cytologic lesions in
      their cervix is unclear. We performed a meta-analysis to assess the accuracy of
      human papillomavirus (HPV) DNA testing as an alternative to repeat cytology in
      women who had equivocal results on a previous Pap smear. METHODS: Data were
      extracted from articles published between 1992 and 2002 that contained results of
      virologic and cytologic testing followed by colposcopically directed biopsy in
      women with an index smear showing atypical cells of undetermined significance
      (ASCUS). Fifteen studies were identified in which HPV triage and the histologic
      outcome (presence or absence of a cervical intraepithelial neoplasia of grade II
      or worse [CIN2+]) was documented. Nine, seven, and two studies also documented
      the accuracy of repeat cytology when the cutoff for abnormal cytology was set at
      a threshold of ASCUS or worse, low-grade squamous intraepithelial lesion (LSIL)
      or worse, or high-grade squamous intraepithelial lesion (HSIL) or worse,
      respectively. Random-effects models were used for pooling of accuracy parameters
      in case of interstudy heterogeneity. Differences in accuracy were assessed by
      pooling the ratio of the sensitivity (or specificity) of HPV testing to that of
      repeat cytology. RESULTS: The sensitivity and specificity were 84.4% (95%
      confidence interval [CI] = 77.6% to 91.1%) and 72.9% (95% CI = 62.5% to 83.3%),
      respectively, for HPV testing overall and 94.8% (95% CI = 92.7% to 96.9%) and
      67.3% (95% CI = 58.2% to 76.4%), respectively, for HPV testing in the eight
      studies that used the Hybrid Capture II assay. Sensitivity and specificity of
      repeat cytology at a threshold for abnormal cytology of ASCUS or worse was 81.8%
      (95% CI = 73.5% to 84.3%) and 57.6% (95% CI = 49.5% to 65.7%), respectively.
      Repeat cytology that used higher cytologic thresholds yielded substantially lower
      sensitivity but higher specificity than triage with the Hybrid Capture II assay.
      The ratio of the sensitivity of the Hybrid Capture II assay to that of repeat
      cytology at a threshold of ASCUS or worse pooled from the four studies that used
      both triage tests was 1.16 (95% CI = 1.04 to 1.29). The specificity ratio was not
      statistically different from unity. CONCLUSION: The published literature
      indicates that the Hybrid Capture II assay has improved accuracy (higher
      sensitivity, similar specificity) than the repeat Pap smear using the threshold
      of ASCUS for an outcome of CIN2+ among women with equivocal cytologic results.
      The sensitivity of triage at higher cytologic cutoffs is poor.

PMID- 14970278
TI  - TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia.
AB  - BACKGROUND: Cervical carcinogenesis is initiated by infection with high-risk
      (i.e., carcinogenic) human papillomavirus (HPV) types. The subsequent progression
      from premalignant cervical intraepithelial neoplasia (CIN) to invasive cancer is
      driven by both genetic and epigenetic processes. We assessed the role of the gene
      encoding the adhesion molecule tumor suppressor in lung cancer 1 (TSLC1) in this
      progression. METHODS: We analyzed TSLC1 gene expression by real-time quantitative
      reverse transcription-polymerase chain reaction, promoter methylation by sodium
      bisulfite genomic DNA sequencing, and allelic loss by microsatellite analysis in
      primary keratinocytes, in four non-tumorigenic HPV-immortalized human
      keratinocyte cell lines, and in 11 human cervical cancer cell lines that were
      positive for a high-risk HPV DNA type and in normal cervical epithelial cells. We
      transfected cervical cancer SiHa cells that did not express TSLC1 mRNA with an
      expression vector containing the TSLC1 complementary DNA (cDNA) or an empty
      vector and analyzed transfectants for anchorage-independent growth and
      tumorigenicity in nude mice. We also examined TSLC1 promoter methylation in
      premalignant cervical lesions and in cervical carcinomas and smears. All
      statistical tests were two-sided. RESULTS: TSLC1 mRNA was strongly reduced,
      relative to levels in primary keratinocytes, or absent in 10 (91%) of 11 cervical
      carcinoma cell lines but in none (0%) of the four HPV-immortalized cell lines
      (difference = 91%, 95% confidence interval [CI] = 74% to 100%; P =.004). The
      TSLC1 promoter was hypermethylated, relative to normal foreskin and cervical
      epithelial cells, in nine (82%) of the 11 cervical carcinoma cell lines but in
      none (0%) of the four HPV-immortalized cell lines (difference = 82%, 95 CI = 59%
      to 100%; P =.01). Seven (88%, 95% CI = 47% to 100%) of the eight SiHa/TSLC1
      transfectants displayed a marked reduction in anchorage-independent growth (i.e.,
      0-100 colonies per 5000 cells) compared with none of the four (0%, 95% CI = 0% to
      60%) SiHa transfectants bearing the empty vector (i.e., SiHa/hygro transfectants;
      difference = 88%, 95% CI = 65% to 100%; P =.01) or untransfected SiHa cells. All
      seven mice (100%, 95% CI = 59% to 100%) injected with untransfected SiHa cells or
      SiHa/hygro transfectants displayed tumors of at least 50 mm(3) by 2-6 weeks after
      injection compared with none of eight mice (0%, 95% CI = 0% to 37%) injected with
      the SiHa/TSLC1 transfectants (difference = 100%, 95% CI = 68% to 100%; P<.001).
      We detected TSLC1 promoter hypermethylation in seven (35%, 95% CI = 15% to 59%)
      of 20 high-grade CIN lesions (i.e., CIN II and III) and in 30 (58%, 95% CI = 43%
      to 71%) of 52 cervical squamous cell carcinomas compared with none (0%, 95% CI =
      0% to 34%) of nine normal cervical epithelial biopsy samples and none (0%, 95% CI
      = 0% to 22%) of 12 CIN I lesions (P<.001 for cervical squamous cell cancer versus
      normal epithelial biopsy samples plus CIN I lesions). CONCLUSIONS: TSLC1 gene
      silencing via promoter hypermethylation is a frequent event in the progression
      from high-risk HPV-containing, high-grade CIN lesions to invasive cervical
      cancer.

PMID- 14970279
TI  - Aspirin and the risk of Hodgkin's lymphoma in a population-based case-control
      study.
AB  - BACKGROUND: Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is
      associated with decreased risk of several malignancies. NSAIDs may prevent cancer
      development by blocking the cyclooxygenase-catalyzed synthesis of proinflammatory
      prostaglandins. Aspirin may also protect against Hodgkin's lymphoma by inhibiting
      transcription factor nuclear factor kappaB (NF-kappaB), which is necessary for
      immune function and the survival of Hodgkin's lymphoma cells. We examined the
      association between regular analgesic use and the risk of Hodgkin's lymphoma.
      METHODS: A population-based case-control study of 565 case patients with
      Hodgkin's lymphoma and 679 control subjects was conducted in the metropolitan
      area of Boston, Massachusetts, and in the state of Connecticut. Participants
      reported their average use of aspirin, non-aspirin NSAIDs, and acetaminophen over
      the previous 5 years. Regular analgesic use was defined as consumption of at
      least two tablets per week on average over the preceding 5 years; non-regular use
      was defined as consumption of fewer than two tablets per week. RESULTS: The risk
      of Hodgkin's lymphoma associated with regular aspirin use was statistically
      significantly lower (odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.42
      to 0.85) than that associated with non-regular aspirin use. The risk was not
      associated with use of other non-aspirin NSAIDs (OR = 0.97, 95% CI = 0.73 to
      1.30). However, the risk associated with regular acetaminophen use was
      statistically significantly higher (OR = 1.72, 95% CI = 1.29 to 2.31) than that
      associated with non-regular use. CONCLUSION: The inverse association between
      aspirin, but not other NSAIDs, and Hodgkin's lymphoma suggests that NF-kappaB
      signaling may play a key role in Hodgkin's lymphoma pathogenesis.

PMID- 14970280
TI  - Cost-effectiveness of aspirin chemoprevention for Barrett's esophagus.
AB  - BACKGROUND: Recent data suggest that nonsteroidal anti-inflammatory drugs,
      including aspirin, may prevent the progression of Barrett's esophagus to
      adenocarcinoma. However, use of aspirin is associated with numerous potential
      complications, including gastrointestinal bleeding and hemorrhagic strokes. We
      used a modeling approach to determine and compare the effectiveness and cost
      effectiveness of aspirin with and without endoscopic surveillance to prevent
      esophageal adenocarcinoma. METHODS: A Markov Monte Carlo decision model was
      constructed to compare four strategies for management of Barrett's esophagus:
      aspirin therapy, endoscopic surveillance with biopsies, both, or neither.
      Patients who took a daily enteric-coated aspirin were modeled to have a 50%
      reduction in the incidence of esophageal adenocarcinoma but could have
      complications related to therapy, at which point the aspirin was discontinued.
      Potential cardiac benefits of aspirin and its role in the chemoprevention of
      other cancers were not included in the analysis. The analysis was from a societal
      perspective from age 55 years until death. Sensitivity analyses were performed to
      investigate the effects of changes in model parameters on estimated costs and
      effectiveness outcomes across a wide range of assumptions. RESULTS: Aspirin
      therapy was more effective and less costly than no therapy, resulting in 0.19
      more quality-adjusted life years (QALYs). The combination of aspirin and
      endoscopic surveillance produced 0.27 more QALYs than no therapy at a cost of
      13,400 U.S. dollars more, for an associated incremental cost-effectiveness ratio
      of 49,600 U.S. dollars/QALY. Aspirin use in combination with endoscopic
      surveillance dominated endoscopic surveillance alone, resulting in 0.06 more
      QALYs and 11,400 U.S. dollars less cost. The model's results were sensitive to
      increasing age and to decreased benefit or delay in aspirin's chemopreventive
      efficacy. CONCLUSION: Using published values of parameters, regardless of whether
      a patient undergoes endoscopic surveillance, aspirin use in the management of
      Barrett's esophagus appears to be a cost-effective strategy to prevent esophageal
      adenocarcinoma.

PMID- 14970281
TI  - Granulocyte-macrophage colony-stimulating factor gene-modified autologous tumor
      vaccines in non-small-cell lung cancer.
AB  - To evaluate the feasibility, safety, and efficacy of vaccination with autologous
      tumor cells genetically modified with an adenoviral vector (Ad-GM) to secrete
      human granulocyte-macrophage colony-stimulating factor (GM-CSF), we conducted a
      phase I/II multicenter trial in patients with early and advanced stage non-small
      cell lung cancer (NSCLC). Vaccines were generated from autologous tumor harvests.
      Intradermal injections were given every 2 weeks for a total of three to six
      vaccinations. Tumors were harvested from 83 patients, 20 with early-stage NSCLC
      and 63 with advanced- stage NSCLC; vaccines were successfully manufactured for 67
      patients, and 43 patients were vaccinated. The most common toxicity was a local
      injection-site reaction (93%). Three of 33 advanced-stage patients, two with
      bronchioloalveolar carcinoma, had durable complete tumor responses (lasting 6,
      18, and >or=22 months). Longer survival was observed in patients receiving
      vaccines secreting GM-CSF at more than 40 ng/24 h per 10(6) cells (median
      survival = 17 months, 95% confidence interval [CI] = 6 to 23 months) than in
      patients receiving vaccines secreting less GM-CSF (median survival = 7 months,
      95% CI = 4 to 10 months) (P =.028), suggesting a vaccine dose-related survival
      advantage.

PMID- 14970282
TI  - Cancer information on the world wide Web: gross characteristics.

PMID- 14970283
TI  - Re: Selenium supplementation and secondary prevention of nonmelanoma skin cancer
      in a randomized trial.

PMID- 14970285
TI  - Re: A prospective study of pigmentation, sun exposure, and risk of cutaneous
      malignant melanoma in women.

PMID- 14970286
TI  - Re: A prospective study of pigmentation, sun exposure, and risk of cutaneous
      malignant melanoma in women.

PMID- 14970289
TI  - Male breast cancer during finasteride therapy.

PMID- 14970290
TI  - Assessing clinical competency in medical senior house officers: how and why
      should we do it?
AB  - Most consultants are involved in the training and assessment of several grades of
      doctors in training especially senior house officers (SHOs) and specialist
      registrars. In the medical and other specialties there is an increasing trend
      towards assessing junior doctors' competency using the record of in-training
      assessment process for specialist registrars and using the Royal College of
      Physicians folder to record competences of medical SHOs. It is necessary to
      consider why there is a need to assess competency, how it may be done
      practically, and the advantages and disadvantages of this system of assessment.
      There are considerable hurdles to the implementation of this system in the
      medical specialties within today's NHS and the organisation may need to undergo
      fairly radical change to facilitate this system.

PMID- 14970291
TI  - Body dysmorphic disorder.
AB  - Body dysmorphic disorder (BDD) is defined as a preoccupation with an "imagined"
      defect in one's appearance. Alternatively, where there is a slight physical
      anomaly, then the person's concern is markedly excessive. The preoccupation is
      associated with many time consuming rituals such as mirror gazing or constant
      comparing. BDD patients have a distorted body image, which may be associated with
      bullying or abuse during childhood or adolescence. Such patients have a poor
      quality of life, are socially isolated, depressed, and at high risk of committing
      suicide. They often have needless dermatological treatment and cosmetic surgery.
      The condition is easily trivialised and stigmatised. There is evidence for the
      benefit of cognitive behaviour therapy and selective serotonin reuptake
      inhibitors in high doses for at least 12 weeks, as in the treatment of obsessive
      compulsive disorder. There is no evidence of any benefit of antipsychotic drugs
      or other forms of psychotherapy.

PMID- 14970292
TI  - History of asbestos related disease.
AB  - The first medical article on the hazards of asbestos dust appeared in the British
      Medical Journal in 1924. Following inquiries by Edward Merewether and Charles
      Price, the British government introduced regulations to control dangerous dust
      emissions in UK asbestos factories. Until the 1960s these appeared to have
      addressed the problem effectively. Only then, with the discoveries that
      mesothelioma was an asbestos related disease and that workers other than those
      employed in the dustiest parts of asbestos factories were at risk, were the
      nature and scale of the hazard reassessed. In Britain, America, and elsewhere new
      and increasingly strict regulations were enacted.

PMID- 14970293
TI  - Spilled gall stones during laparoscopic cholecystectomy: a review of the
      literature.
AB  - Laparoscopic cholecystectomy is associated with spillage of gall stones in 5%-40%
      of procedures, but complications occur very rarely. There are, however, isolated
      case reports describing a range of complications occurring both at a distance
      from and near to the subhepatic area. This review looks into the various modes of
      presentation, ways to minimise spillage, treating the complications, and the
      legal implications.

PMID- 14970294
TI  - Neonatal congenital microvillus atrophy.
AB  - Congenital microvillous atrophy (CMVA) is the leading cause of neonatal secretory
      diarrhoea with onset either in the first 72 hours of life (early onset) or at 6-8
      weeks after birth (late onset). To date over 30 cases have been reported
      worldwide. The prognosis for this life threatening condition continues to be
      poor. Therapeutic agents like somatostatin and epidermal growth factor are either
      ineffective or of marginal benefit. Overall five year survival after small bowel
      transplantation is currently approximately 50%. The following brief review is
      aimed towards helping neonatologists/perinatologists in the early diagnosis, and
      management of CMVA and in counselling the parents appropriately.

PMID- 14970295
TI  - Echocardiography and the general physician.
AB  - Doctors from many medical specialties request echocardiography as part of their
      assessment of patients with a wide range of pathology. Recent advances in the
      technology and techniques of echocardiography are discussed. The role of
      echocardiography in acute medicine is reviewed and its place in general medicine
      is also discussed.

PMID- 14970296
TI  - Poor outcome in primary intracerebral haemorrhage: results of a matched
      comparison.
AB  - BACKGROUND: Primary intracerebral haemorrhage (PICH) is associated with a poorer
      outcome than cerebral infarction. This study aimed to determine whether this is
      explained by the clinical severity of stroke. METHODS: An observational study of
      outcome in consecutive admissions with acute PICH and ischaemic stroke was
      undertaken. A nested case-control analysis, matched on a 1:2 basis for age, pre
      stroke disability, early neurological impairment (Scandinavian Stroke Scale;
      SSS), and Oxfordshire Community Stroke Project classification was then performed.
      Follow up was at 30 days and at hospital discharge. RESULTS: Overall, 679
      subjects were included in the analysis. Of these, 53 (8%) had PICH; this group
      had more severe initial neurological impairment (day 3 SSS 28 v 45 points,
      p<0.001) and a higher prevalence of total anterior circulation strokes (55% v
      21%, p<0.001) than did the group admitted with ischaemic strokes. Outcomes were
      poorer in the PICH group, with 36% inpatient mortality and 68% of survivors
      having a day 30 modified Rankin Scale (MRS) of at least 3 (compared with 13% and
      52%, respectively, in the ischaemic stroke group). Following matching for
      baseline clinical characteristics, the PICH group had a higher mortality, but
      this was not statistically significant; the day 30 MRS and institutionalisation
      rates in survivors were similar in the matched haemorrhage and infarct groups.
      CONCLUSIONS: Compared with ischaemic stroke, PICH is associated with higher
      mortality and increased disability in survivors. The severity of clinical stroke
      is a major contributor to these poor outcomes; baseline characteristics, however,
      do not fully explain outcome differences.

PMID- 14970297
TI  - A questionnaire survey of stress and bullying in doctors undertaking research.
AB  - BACKGROUND: Research is an increasingly important aspect of higher medical
      training for many doctors. Studies investigating sources of stress, isolation,
      and workplace bullying have not previously sought information in this setting.
      METHODS: An internet based questionnaire survey of doctors undertaking research
      (n = 259) was conducted to examine stressors and levels of job satisfaction in
      this potentially vulnerable group. In order to assess overall levels of
      satisfaction, we asked whether doctors would recommend their research post to a
      colleague. RESULTS: There was a statistically significant association between
      those who would not recommend their post to a colleague and those who had
      difficulties in arranging funding and in writing up (p<0.001). Further
      significant correlations were found between dissatisfaction with the post and
      lack of help, support, and advice from supervisors and colleagues, wanting to
      change supervisors, experience of the major categories of workplace bullying, and
      having an inadequate clinical commitment (p<0.001). When the significant
      variables were entered into a multivariate analysis, the results showed that
      dissatisfaction was associated with wanting to change supervisors and with a
      threat to professional status. CONCLUSIONS: Stress and bullying are common in
      doctors undertaking research. These findings have important implications for
      medical training and for doctors choosing research projects. Setting up systems
      of support may have important benefits.

PMID- 14970298
TI  - Clinical and laboratory observations of tuberculosis at a Mumbai (India) clinic.
AB  - OBJECTIVES: To study the positivity of sputum acid fast bacilli (AFB) smears in
      patients with pulmonary tuberculosis using 24 hour sputum collection. To detect
      HIV seropositivity in patients suffering from tuberculosis, and to analyse the
      pattern of tuberculosis disease in this subgroup. To determine the outcome of
      patients treated with directly observed therapy. SETTING: The tuberculosis
      referral unit of a tertiary care hospital. DESIGN: A total of 893 consecutive
      patients with tuberculosis, diagnosed between 1 November 2000 and 30 September
      2002, were included in the study. An HIV test was performed in all patients, with
      adequate counselling and informed consent. Treatment was prescribed as per World
      Health Organisation treatment categories. RESULTS: Out of 893 patients with
      tuberculosis, 695 had pulmonary tuberculosis and 198 had extrapulmonary
      tuberculosis. Out of the 695 pulmonary tuberculosis patients, 673 (96.8%) were
      sputum smear AFB positive. Overall, 71 patients (8.0%) were HIV positive. The
      pattern of tuberculosis was the same in HIV seropositive and seronegative
      patients. Treatment outcome could be analysed in 112 out of 150 patients: 78
      patients (70%) were declared cured or completed treatment. CONCLUSIONS: Sputum
      smear AFB could be a very sensitive test when a large quantity of sputum is used.
      The presence of HIV coinfection does not alter the clinical presentation. Only
      70% of patients treated were cured/completed treatment, in spite of a strict
      directly observed therapy.

PMID- 14970299
TI  - Retired physicians: a survey study by the Turkish Medical Association.
AB  - BACKGROUND: The aim of this study was to assess the quality of life of retired
      Turkish physicians. The focus was on their working conditions, their health
      status, and the impact of their disabilities on activities of daily life.
      METHODS: The survey was conducted using a 35 item questionnaire, which was
      distributed to the local medical chambers allied with the Turkish Medical
      Association and thereafter was mailed to retirees aged 65 years and older.
      RESULTS: Out of 680 physicians, 391 (57.5%) responded, and percentages are
      expressed according to the number of physicians answering each question. The ages
      of the physicians ranged between 65 years and 91 years with a mean of 72.57+/
      5.22 years. Overall, 236 physicians (60.8%) were still actively carrying on their
      profession, and 152 (39.2%) were not. Of the physicians who were working, 0.8%
      classified their working conditions as very bad, 9.7% as unsatisfactory, 37.7% as
      satisfactory, 33.6% as good, and 18.2% as excellent. The number of physicians
      with a disability was 42 (11.8%). The number of days on which physicians were
      hindered in their daily tasks ranged between 0 and 30 days with a mean (SD) of
      1.55 (4.88) days, and the amount of sick leave ranged between 0 and 365 days with
      a mean of 2.25 (21.08) days. CONCLUSION: It is believed that planning for
      retirement in all its aspects should be a legitimate concern of all physicians.
      Recommendations for future retirees or the construction of guidelines for making
      this time of life enriching and a period of intellectual growth are awaited.

PMID- 14970300
TI  - Evaluation of flexible sigmoidoscopy as an investigation for "left sided"
      colorectal symptoms.
AB  - BACKGROUND: Colonoscopy is the best way of imaging the colon with concurrent
      biopsy and treatment. However it is expensive, requires full bowel preparation,
      and carries a risk of complications. Flexible sigmoidoscopy is an alternative way
      to investigate symptoms that raise the suspicion of a lesion of the rectum or
      left colon. AIM OF THE STUDY: To evaluate flexible sigmoidoscopy as the main
      investigation for "left sided" colorectal symptoms. METHODS: The clinical records
      of 317 patients who were assessed at a colorectal specialist clinic and were
      thought to have a suspicion of a lesion of the rectum or left colon were
      retrospectively reviewed. All patients had flexible sigmoidoscopy as the primary
      investigation. Primary outcome was the diagnostic yield of flexible sigmoidoscopy
      and secondary outcomes were any additional colonic investigations required,
      failure rates, and complication rates. RESULTS: Three hundred and sixteen
      patients who had flexible sigmoidoscopy with the above criteria were
      retrospectively analysed. Twenty four procedures (7.6%) had to be abandoned
      because of poor bowel preparation. The examination was considered complete when
      it reached the splenic flexure, which was the case in 205 cases (65%). In 137
      flexible sigmoidoscopies (43.3%) there were no abnormal findings. Of the
      remaining 179 a carcinoma of the rectum or colon was found in 28 cases (8.8%) and
      one or more polyps was found in 57 (18%) cases. On the basis of the findings it
      was calculated that 31% of the patients would require an additional investigation
      for further imaging of the right colon. DISCUSSION: Although flexible
      sigmoidoscopy has a high yield of pathologies when carried out by a specialist
      colorectal clinic, the presence of those pathologies makes the full imaging of
      the whole colon with an additional investigation necessary. Therefore the cost
      efficiency of flexible sigmoidoscopy is questionable. Although flexible
      sigmoidoscopy is indicated for certain patients, it cannot replace colonoscopy as
      the main investigation used by a specialist colorectal clinic.

PMID- 14970301
TI  - Warfarin and celecoxib interaction in the setting of cytochrome P450 (CYP2C9)
      polymorphism with bleeding complication.
AB  - Drug metabolism may be perturbed by genetically determined differences in the
      metabolic activity of cytochrome P450 enzymes. The authors encountered extensive
      bleeding in a patient receiving warfarin for anticoagulation after the
      introduction of celecoxib, an anti-inflammatory drug. As the CYP2C9 enzyme
      metabolises these drugs, it was determined whether variant alleles were
      responsible for altering warfarin handling. Genetic analysis established that the
      patient was a compound heterozygote with CYP2C9*2 and *3 variant alleles, which
      exhibit lower drug metabolising capacity and enhance susceptibility to drug
      toxicity.

PMID- 14970302
TI  - Salmonella osteomyelitis of the thoracic spine: an unusual presentation.
AB  - A case of thoracic vertebral osteomyelitis due to Salmonella enteritidis phage
      type 2 in an immunocompetent patient is reported. The patient initially presented
      with abdominal, urinary and chest symptoms, which were followed by a large
      pleural effusion. The infection was successfully treated with ciprofloxacin. This
      is the only case of salmonella thoracic vertebral osteomyelitis in an
      immunocompetent patient reported in the English literature.

PMID- 14970303
TI  - Resolution of cryptosporidiosis with probiotic treatment.
AB  - Cryptosporidium infection is usually self limited, but can be a life threatening
      illness in immunocompromised patients. Probiotics have been used successfully in
      the treatment of acute diarrhoea and they have also been shown to limit
      Cryptosporidium parvum infection in animal models. The first case of successful
      resolution of prolonged cryptosporidiosis with probiotic treatment is reported.

PMID- 14970304
TI  - Co-occurrence of thyroid binding globulin excess and a pituitary macroadenoma
      containing thyroid stimulating hormone-producing cells.
AB  - A patient is described in whom thyroid binding globulin (TBG) excess was found in
      association with a pituitary macroadenoma containing thyroid stimulating hormone
      (TSH)-producing cells, and the potential for diagnostic confusion arising from
      this unusual combination of endocrine disorders is discussed. The patient
      presented with visual field disturbance, and magnetic resonance imaging led to
      the diagnosis of a pituitary tumour. Raised levels of total thyroxine and
      triiodothyronine along with normal TSH levels suggested the possibility of a TSH
      secreting pituitary adenoma. Immunostaining of the tumour removed at
      transsphenoidal surgery confirmed the presence of TSH-producing cells. When
      raised total thyroxine and triiodothyronine levels persisted postoperatively, the
      diagnosis of TBG excess was confirmed. Use of free, rather than total, thyroid
      hormone assays would almost certainly have prevented the diagnostic confusion
      concerning possible TSH-secreting pituitary adenoma, but may have resulted in the
      TBG excess being overlooked entirely.

PMID- 14970305
TI  - Long uvula: an unusual cause of chronic cough.
AB  - Chronic cough is a distressing symptom for patients and parents in paediatric
      practice. Investigations of the child with persistent cough can be simple or
      complex depending on the underlying cause. There are some unusual reasons for
      chronic cough, which need to be kept in mind when investigating the cause. A case
      of a long, floppy uvula causing chronic cough through mechanical irritation of
      upper airway is reported.

PMID- 14970306
TI  - A patient with recurrent syncope.

PMID- 14970307
TI  - Digital gangrene: an unusual cause.

PMID- 14970308
TI  - Tachycardia in the presence of a pacemaker.

PMID- 14970312
TI  - Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol
      metabolism in brain aging and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is an age-related disorder characterized by deposition
      of amyloid beta-peptide (Abeta) and degeneration of neurons in brain regions such
      as the hippocampus, resulting in progressive cognitive dysfunction. The
      pathogenesis of AD is tightly linked to Abeta deposition and oxidative stress,
      but it remains unclear as to how these factors result in neuronal dysfunction and
      death. We report alterations in sphingolipid and cholesterol metabolism during
      normal brain aging and in the brains of AD patients that result in accumulation
      of long-chain ceramides and cholesterol. Membrane-associated oxidative stress
      occurs in association with the lipid alterations, and exposure of hippocampal
      neurons to Abeta induces membrane oxidative stress and the accumulation of
      ceramide species and cholesterol. Treatment of neurons with alpha-tocopherol or
      an inhibitor of sphingomyelin synthesis prevents accumulation of ceramides and
      cholesterol and protects them against death induced by Abeta. Our findings
      suggest a sequence of events in the pathogenesis of AD in which Abeta induces
      membrane-associated oxidative stress, resulting in perturbed ceramide and
      cholesterol metabolism which, in turn, triggers a neurodegenerative cascade that
      leads to clinical disease.

PMID- 14970313
TI  - Ghrelin cells replace insulin-producing beta cells in two mouse models of
      pancreas development.
AB  - The pancreatic islet is necessary for maintaining glucose homeostasis. Within the
      pancreatic islet, the homeodomain protein Nkx2.2 is essential for the
      differentiation of all insulin-producing beta cells and a subset of glucagon
      producing alpha cells (1). Mice lacking Nkx2.2 have relatively normal sized
      islets, but a large number of cells within the mutant islet fail to produce any
      of the four major islet hormones. In this study we demonstrate that Nkx2.2 mutant
      endocrine cells have been replaced by cells that produce ghrelin, an appetite
      promoting peptide predominantly found in the stomach. Intriguingly, normal mouse
      pancreas also contains a small population of ghrelin-producing cells, defining a
      new islet "epsilon" cell population. The expansion of ghrelin-producing cells at
      the expense of beta cells may be a general phenomenon, because we demonstrate
      that Pax4 mutant mice display a similar phenotype. We propose that insulin and
      ghrelin cells share a common progenitor and that Nkx2.2 and Pax4 are required to
      specify or maintain differentiation of the beta cell fate. This finding also
      suggests that there is a genetic component underlying the balance between insulin
      and ghrelin in regulating glucose metabolism.

PMID- 14970317
TI  - Early protection against pathogenic virus infection at a mucosal challenge site
      after vaccination with attenuated simian immunodeficiency virus.
AB  - Atraumatic application of attenuated SIVmac239 Delta nef vaccine to the tonsils
      of rhesus macaques provided protection against challenge 26 weeks later with
      infectious SIVmac251 applied through this route. Early events at the mucosal
      portal of entry of challenge virus were followed. Wild-type virus was detected in
      nonvaccinated controls by day 4, and then simian immunodeficiency virus (SIV)
      replicated vigorously at days 7 and 14. In contrast, a challenge of 10 of 10
      vaccinees with SIV did not significantly raise RNA levels in the plasma or
      increase infected cells in lymphoid tissues, as assessed by single-cell labeling
      for viral RNA and nef protein. Vaccine virus was found in the tonsils of all
      vaccinees, but challenge virus was only detected at this portal of entry in 4 of
      10 monkeys. In the tonsil, the challenge virus did not induce an expansion of
      perforin(+) killer cells. However, there was a significant increase in gamma
      delta T cells and mature dendritic cells relative to unvaccinated controls.
      Therefore, during tonsillar SIV Delta nef vaccination, infection is blocked early
      at the entry portal, which we propose is due in part to innate functions of gamma
      delta T and dendritic cells.

PMID- 14970324
TI  - Digital karyotyping identifies thymidylate synthase amplification as a mechanism
      of resistance to 5-fluorouracil in metastatic colorectal cancer patients.
AB  - Resistance to chemotherapy is a major cause of mortality in advanced cancer
      patients. In this study, digital karyotyping was used to search for genomic
      alterations in liver metastases that were clinically resistant to 5-fluorouracil
      (5-FU). In two of four patients, we identified amplification of an approximately
      100-kb region on 18p11.32 that was of particular interest because it contained
      the gene encoding thymidylate synthase (TYMS), a molecular target of 5-FU.
      Analysis of TYMS by fluorescence in situ hybridization identified TYMS gene
      amplification in 23% of 31 5-FU-treated cancers, whereas no amplification was
      observed in metastases of patients that had not been treated with 5-FU. Patients
      with metastases containing TYMS amplification had a substantially shorter median
      survival (329 days) than those without amplification (1,021 days, P <0.01). These
      data suggest that genetic amplification of TYMS is a major mechanism of 5-FU
      resistance in vivo and have important implications for the management of
      colorectal cancer patients with recurrent disease.

PMID- 14970327
TI  - Inactivation of a Pseudomonas aeruginosa quorum-sensing signal by human airway
      epithelia.
AB  - Mammalian airways protect themselves from bacterial infection by using multiple
      defense mechanisms including antimicrobial peptides, mucociliary clearance, and
      phagocytic cells. We asked whether airways might also target a key bacterial cell
      cell communication system, quorum-sensing. The opportunistic pathogen Pseudomonas
      aeruginosa uses two quorum-sensing molecules, N-(3-oxododecanoyl)-l-homoserine
      lactone (3OC12-HSL) and N-butanoyl-l-homoserine lactone (C4-HSL), to control
      production of extracellular virulence factors and biofilm formation. We found
      that differentiated human airway epithelia inactivated 3OC12-HSL. Inactivation
      was selective for acyl-HSLs with certain acyl side chains, and C4-HSL was not
      inactivated. In addition, the capacity for inactivation varied widely in
      different cell types. 3OC12-HSL was inactivated by a cell-associated activity
      rather than a secreted factor. These data suggest that the ability of human
      airway epithelia to inactivate quorum-sensing signal molecules could play a role
      in the innate defense against bacterial infection.

PMID- 14970329
TI  - Regulation of expression of Bcl-2 protein family member Bim by T cell receptor
      triggering.
AB  - Bim, a proapoptotic BH3-only member of the Bcl-2 protein family, is required for
      central and peripheral deletion of T lymphocytes. Mechanisms regulating Bim
      activity in T cells remain poorly understood. We show that expression of Bim is
      up-regulated in human T cells after polyclonal or specific T cell receptor
      triggering. Induction of Bim was affected by the agonistic potency of MHC:peptide
      ligands. Peptides that failed to induce Bim expression, failed to induce
      apoptosis in specific T cells, whereas partially agonistic ligands, which trigger
      death receptor-independent activation-induced cell death (AICD), induced Bim, but
      were inefficient in up-regulating Bcl-X(L). Activation of protein kinase C and
      calcineurin appeared to be necessary and sufficient for Bim up-regulation after T
      cell receptor ligation. Immunosuppressive drugs known to prevent T cell deletion
      in vivo, such as cyclosporin A or FK506, blocked Bim up-regulation and rescued T
      cells from death receptor-independent AICD, whereas rapamycin, which allows the
      development of stable immunological tolerance, did not exhibit these activities.
      These results define a new mode of Bim regulation, strongly implicate Bim as a
      mediator of AICD, and suggest that Bim up-regulation can be targeted to influence
      the outcome of specific immune responses.

PMID- 14970331
TI  - Glutamate-183 in the conserved TGES motif of domain A of sarcoplasmic reticulum
      Ca2+-ATPase assists in catalysis of E2/E2P partial reactions.
AB  - The recently determined crystal structures of the sarcoplasmic reticulum Ca(2+)
      ATPase show that in the E(1)Ca(2) form, domain A is almost isolated from the
      other cytoplasmic domains, P and N, whereas in E(2), domain A has approached
      domains P and N, with E183 of the highly conserved P-type ATPase signature
      sequence TGES in domain A now being close to the phosphorylated aspartate in
      domain P, thus raising the question whether E183 acquires a catalytic role in
      E(2) and E(2)P conformations. This study compares the partial reactions of mutant
      E183A and wild-type Ca(2+)-ATPase, using transient and steady-state kinetic
      measurements. It is demonstrated that dephosphorylation of the E(2)P
      phosphoenzyme intermediate, as well as reverse phosphorylation of E(2) with P(i),
      is severely inhibited in the mutant. Furthermore, the apparent affinity of E(2)
      for the phosphoryl transition state analog vanadate is reduced by three orders of
      magnitude, consistent with a destabilization of the transition state complex, and
      the mutant displays reduced apparent affinity for P(i) in the E(2) form. The
      E(1)Ca(2) conformation, on the other hand, shows normal phosphorylation with ATP
      and normal Ca(2+) binding properties, and the rates of the conformational
      transitions E(1)PCa(2) --> E(2)P and E(2) --> E(1)Ca(2) are only 2- to 3-fold
      reduced, relative to wild type. These results, which likely can be generalized to
      other P-type ATPases, indicate that E183 is critical for the phosphatase function
      of E(2) and E(2)P, possibly interacting with the phosphoryl group or attacking
      water in the transition state complex, but is of little functional importance in
      E(1) and E(1)P.

PMID- 14970332
TI  - Structure of the multidrug resistance efflux transporter EmrE from Escherichia
      coli.
AB  - Multidrug resistance efflux transporters threaten to reverse the progress
      treating infectious disease by extruding a wide range of drug and other cytotoxic
      compounds. One such drug transporter, EmrE, from the small multidrug resistance
      family, utilizes proton gradients as an energy source to drive substrate
      translocation. In an effort to understand the molecular structural basis of this
      transport mechanism, we have determined the structure of EmrE from Escherichia
      coli to 3.8 A. EmrE is a tetramer comprised of two conformational heterodimers
      related by a pseudo two-fold symmetry axis perpendicular to the cell membrane.
      Based on the structure and biochemical evidence, we propose a mechanism by which
      EmrE accomplishes multidrug efflux by coupling conformational changes between two
      heterodimers with proton gradient. Because of its simplicity and compact size,
      the structure of EmrE can serve as an ideal model for understanding the general
      structural basis of proton:drug antiport for other drug efflux systems.

PMID- 14970333
TI  - Cysteinyl leukotriene 1 receptor controls the severity of chronic pulmonary
      inflammation and fibrosis.
AB  - The cysteinyl leukotrienes (cys-LTs), leukotriene (LT) C(4), LTD(4), and LTE(4),
      are smooth muscle constrictors that signal via the CysLT(1) receptor. Here we
      report that the cys-LTs play an important role in chronic pulmonary inflammation
      with fibrosis induced by bleomycin in mice. Targeted disruption of LTC(4)
      synthase, the pivotal enzyme for cys-LT biosynthesis, protected significantly
      against alveolar septal thickening by macrophages and fibroblasts and collagen
      deposition. In contrast, targeted disruption of the CysLT(1) receptor
      significantly increased both the concentration of cys-LTs in the bronchoalveolar
      lavage fluid and the magnitude of septal thickening as defined by morphology,
      digital image analysis, and deposition of reticular fibers. These findings change
      our understanding of the pathobiology mediated by the cys-LTs by revealing their
      role in chronic inflammation with fibrosis, likely via the CysLT(2) receptor, and
      by uncovering a dual role for the CysLT(1) receptor, namely proinflammatory acute
      constriction of smooth muscle and antiinflammatory counteraction of chronic
      injury.

PMID- 14970334
TI  - Correspondence of presaccadic activity in the monkey primary visual cortex with
      saccadic eye movements.
AB  - We continuously scan the visual world via rapid or saccadic eye movements. Such
      eye movements are guided by visual information, and thus the oculomotor
      structures that determine when and where to look need visual information to
      control the eye movements. To know whether visual areas contain activity that may
      contribute to the control of eye movements, we recorded neural responses in the
      visual cortex of monkeys engaged in a delayed figure-ground detection task and
      analyzed the activity during the period of oculomotor preparation. We show that
      approximately 100 ms before the onset of visually and memory-guided saccades
      neural activity in V1 becomes stronger where the strongest presaccadic responses
      are found at the location of the saccade target. In addition, in memory-guided
      saccades the strength of presaccadic activity shows a correlation with the onset
      of the saccade. These findings indicate that the primary visual cortex contains
      saccade-related responses and participates in visually guided oculomotor
      behavior.

PMID- 14970339
TI  - Comparisons of pollen coat genes across Brassicaceae species reveal rapid
      evolution by repeat expansion and diversification.
AB  - Reproductive genes and traits evolve rapidly in many organisms, including
      mollusks, algae, and primates. Previously we demonstrated that a family of
      glycine-rich pollen surface proteins (GRPs) from Arabidopsis thaliana and
      Brassica oleracea had diverged substantially, making identification of homologous
      genes impossible despite a separation of only 20 million years. Here we address
      the molecular genetic mechanisms behind these changes, sequencing the eight
      members of the GRP cluster, along with 11 neighboring genes in four related
      species, Arabidopsis arenosa, Olimarabidopsis pumila, Capsella rubella, and
      Sisymbrium irio. We found that GRP genes change more rapidly than their
      neighbors; they are more repetitive and have undergone substantially more
      insertion/deletion events while preserving repeat amino acid composition. Genes
      flanking the GRP cluster had an average K(a)/K(s) approximately 0.2, indicating
      strong purifying selection. This ratio rose to approximately 0.5 in the first GRP
      exon, indicating relaxed selective constraints. The repetitive nature of the
      second GRP exon makes alignment difficult; even so, K(a)/K(s) within the
      Arabidopsis genus demonstrated an increase that correlated with exon length. We
      conclude that rapid GRP evolution is primarily due to duplication, deletion, and
      divergence of repetitive sequences. GRPs may mediate pollen recognition and
      hydration by female cells, and divergence of these genes could correlate with or
      even promote speciation. We tested cross-species interactions, showing that the
      ability of A. arenosa stigmas to hydrate pollen correlated with GRP divergence
      and identifying A. arenosa as a model for future studies of pollen recognition.

PMID- 14970340
TI  - Identification of a second bovine amyloidotic spongiform encephalopathy:
      molecular similarities with sporadic Creutzfeldt-Jakob disease.
AB  - Transmissible spongiform encephalopathies (TSEs), or prion diseases, are
      mammalian neurodegenerative disorders characterized by a posttranslational
      conversion and brain accumulation of an insoluble, protease-resistant isoform
      (PrP(Sc)) of the host-encoded cellular prion protein (PrP(C)). Human and animal
      TSE agents exist as different phenotypes that can be biochemically differentiated
      on the basis of the molecular mass of the protease-resistant PrP(Sc) fragments
      and the degree of glycosylation. Epidemiological, molecular, and transmission
      studies strongly suggest that the single strain of agent responsible for bovine
      spongiform encephalopathy (BSE) has infected humans, causing variant Creutzfeldt
      Jakob disease. The unprecedented biological properties of the BSE agent, which
      circumvents the so-called "species barrier" between cattle and humans and adapts
      to different mammalian species, has raised considerable concern for human health.
      To date, it is unknown whether more than one strain might be responsible for
      cattle TSE or whether the BSE agent undergoes phenotypic variation after natural
      transmission. Here we provide evidence of a second cattle TSE. The disorder was
      pathologically characterized by the presence of PrP-immunopositive amyloid
      plaques, as opposed to the lack of amyloid deposition in typical BSE cases, and
      by a different pattern of regional distribution and topology of brain PrP(Sc)
      accumulation. In addition, Western blot analysis showed a PrP(Sc) type with
      predominance of the low molecular mass glycoform and a protease-resistant
      fragment of lower molecular mass than BSE-PrP(Sc). Strikingly, the molecular
      signature of this previously undescribed bovine PrP(Sc) was similar to that
      encountered in a distinct subtype of sporadic Creutzfeldt-Jakob disease.

PMID- 14970341
TI  - ADP reduces the oxygen-binding affinity of a sensory histidine kinase, FixL: the
      possibility of an enhanced reciprocating kinase reaction.
AB  - The rhizobial FixL/FixJ system, a paradigm of heme-based oxygen sensors, belongs
      to the ubiquitous two-component signal transduction system. Oxygen-free (deoxy)
      FixL is autophosphorylated at an invariant histidine residue by using ATP and
      catalyzes the concomitant phosphoryl transfer to FixJ, but oxygen binding to the
      FixL heme moiety inactivates the kinase activity. Here we demonstrate that ADP
      acts as an allosteric effector, reducing the oxygen-binding affinity of the
      sensor domain in FixL when it is produced from ATP in the kinase reaction. The
      addition of ADP to a solution of purified wild-type FixL resulted in an
      approximately 4- to 5-fold decrease in oxygen-binding affinity in the presence of
      FixJ. In contrast, phosphorylation-deficient mutants, in which the well conserved
      ATP-binding catalytic site of the kinase domain is impaired, showed no such
      allosteric effect. This discovery casts light on the significance of
      homodimerization of two-component histidine kinases; ADP, generated in the
      phosphorylation reaction in one subunit of the homodimer, enhances the histidine
      kinase activity of the other, analogous to a two-cylinder reciprocating engine by
      reducing the ligand-binding affinity.

PMID- 14970342
TI  - Fluorescence correlation spectroscopy with high-order and dual-color correlation
      to probe nonequilibrium steady states.
AB  - In living cells, biochemical reaction networks often function in nonequilibrium
      steady states. Under these conditions, the networks necessarily have cyclic
      reaction kinetics that are maintained by sustained constant input and output,
      i.e., pumping. To differentiate this state from an equilibrium state without
      flux, we propose a microscopic method based on concentration fluctuation
      measurements, via fluorescence correlation spectroscopy, and statistical analyses
      of high-order correlations and cross correlations beyond the standard
      fluorescence correlation spectroscopy autocorrelation. We show that, for
      equilibrium systems with time reversibility, the correlation functions possess
      certain symmetries, the violation of which is a measure of steady-state fluxes in
      reaction cycles. This result demonstrates the theoretical basis for
      experimentally measuring reaction fluxes in a biochemical network in situ and the
      importance of single-molecule measurements in providing fundamental information
      on nonequilibrium steady-states in biochemistry.

PMID- 14970345
TI  - Imprint of evolution on protein structures.
AB  - We attempt to understand the evolutionary origin of protein folds by simulating
      their divergent evolution with a three-dimensional lattice model. Starting from
      an initial seed lattice structure, evolution of model proteins progresses by
      sequence duplication and subsequent point mutations. A new gene's ability to fold
      into a stable and unique structure is tested each time through direct kinetic
      folding simulations. Where possible, the algorithm accepts the new sequence and
      structure and thus a "new protein structure" is born. During the course of each
      run, this model evolutionary algorithm provides several thousand new proteins
      with diverse structures. Analysis of evolved structures shows that later evolved
      structures are more designable than seed structures as judged by recently
      developed structural determinant of protein designability, as well as direct
      estimate of designability for selected structures by thermodynamic sampling of
      their sequence space. We test the significance of this trend predicted on lattice
      models on real proteins and show that protein domains that are found in
      eukaryotic organisms only feature statistically significant higher designability
      than their prokaryotic counterparts. These results present a fundamental view on
      protein evolution highlighting the relative roles of structural selection and
      evolutionary dynamics on genesis of modern proteins.

PMID- 14970346
TI  - Identification of critical residues in GlnB for its activation of NifA activity
      in the photosynthetic bacterium Rhodospirillum rubrum.
AB  - The P(II) regulatory protein family is unusually widely distributed, being found
      in all three domains of life. Three P(II) homologs called GlnB, GlnK, and GlnJ
      have been identified in the photosynthetic bacterium Rhodospirillum rubrum. These
      have roles in at least four distinct functions, one of which is activation of the
      nitrogen fixation-specific regulatory protein NifA. The activation of NifA
      requires only the covalently modified (uridylylated) form of GlnB. GlnK and GlnJ
      are not involved. However, the basis of specificity for different P(II) homologs
      in different processes is poorly understood. We examined this specificity by
      altering GlnJ to support NifA activation. A small number of amino acid
      substitutions in GlnJ were important for this ability. Two (affecting residues 45
      and 54) are in a loop called the T-loop, which contains the site of uridylylation
      and is believed to be very important for contacts with other proteins, but other
      critical residues lie in the C terminus (residues 95-97 and 109-112) and near the
      N terminus (residues 3-5 and 17). Because many of the residues important for
      P(II)-NifA interaction lie far from the T-loop in the known x-ray crystal
      structures of P(II) proteins, our results lead to the hypothesis that the T-loop
      of GlnB is flexible enough to come into proximity with both the C- and N-terminal
      regions of the protein to bind NifA. Finally, the results show that the level of
      P(II) accumulation is also an important factor for NifA activation.

PMID- 14970347
TI  - Outer-surface protein C of the Lyme disease spirochete: a protein induced in
      ticks for infection of mammals.
AB  - Environmentally responsive synthesis of surface proteins represents a hallmark of
      the infectious cycle of the Lyme disease agent, Borrelia burgdorferi. Here we
      created and analyzed a B. burgdorferi mutant lacking outer-surface protein C
      (OspC), an abundant Osp that spirochetes normally synthesize in the tick vector
      during the blood meal and down-regulate after transmission to the mammal. We
      demonstrate that B. burgdorferi strictly requires OspC to infect mice but not to
      localize or migrate appropriately in the tick. The induction of a spirochetal
      virulence factor preceding the time and host in which it is required demonstrates
      a developmental sequence for transmission of this arthropod-borne pathogen.

PMID- 14970352
TI  - The vortex patch problem for the surface quasi-geostrophic equation.
AB  - In this article, the analog of the Euler vortex patch problem for the surface
      quasi-geostrophic equation is considered.

PMID- 14970360
TI  - Three single-nucleotide polymorphisms of the angiotensinogen gene and
      susceptibility to hypertension: single locus genotype vs. haplotype analysis.
AB  - Although some single polymorphism analyses of the angiotensinogen (AGT) gene have
      been found to be associated with hypertension, the results are still
      inconsistent. The objectives of this study are to evaluate the association of the
      genotype and haplotype distributions of three single-nucleotide polymorphisms
      (SNPs) (G-217A, A-6G, and M235T) in the AGT gene with hypertension. In a sample
      of 461 hypertensive and 327 normotensive patients in Taiwan, we found that -217AA
      and -6GG homozygotes conferred independently an increased risk to hypertension (P
      = 0.008 and P = 0.037, respectively), as illustrated by their significant
      associations with hypertension in both single SNP and pair-wise SNPs analyses.
      Meanwhile, a very weak linkage disequilibrium was found between the G-217A and
      the A-6G polymorphisms in terms of r2 (<0.05). On the basis of likelihood ratio
      test, only the set of haplotypes that constituted the A-6G and the M235T
      polymorphisms was associated with hypertension (chi2 = 20.91, P = 0.0008), which
      was mainly due to the increased frequency of the recombinant haplotypes (-6A
      identical with 235M and -6G identical with 235T), and a pathophysiological role
      in the predisposition to hypertension was hence indicated. In functional assays,
      the promoter activities of the haplotypes -217A identical with -6A and -217G
      identical with -6G were significantly higher than the most common haplotype -217G
      identical with -6A. These results highlight the necessity of a thorough analysis
      of all reported variants of a candidate gene in the elucidation of genetic
      susceptibility to a complex disease like hypertension, even when the variants are
      in the same haplotype block.

PMID- 14970361
TI  - Uncoupling protein 2 and 3 in marsupials: identification, phylogeny, and gene
      expression in response to cold and fasting in Antechinus flavipes.
AB  - We searched for the presence of uncoupling protein genes so far unknown in
      marsupials and monotremes and identified uncoupling protein 2 (UCP2) and UCP3
      full-length cDNAs in libraries constructed from the marsupials Antechinus
      flavipes and Sminthopsis macroura. Marsupial UCP2 is 89-90% identical to rodent
      UCP2, whereas UCP3 exhibits 80% identity to mouse UCP3. A phylogenetic tree
      including all known UCPs positions the novel marsupial UCP2 and UCP3 at the base
      of the mammalian orthologs. In the 5'-untranslated region of UCP2 a second open
      reading frame encoding for a 36-amino acid peptide was identified which is highly
      conserved in all vertebrate UCP2 transcripts. Analysis of tissue specificity in
      A. flavipes with homologous cDNA probes revealed ubiquitous presence of UCP2 mRNA
      and striated muscle specificity of UCP3 mRNA resembling the known expression
      pattern in rodents. Neither UCP2 nor UCP3 gene expression was stimulated in
      adipose tissue and skeletal muscle of cold exposed A. flavipes. However, UCP3
      mRNA expression was upregulated 6-fold in heart and 2.5-fold in skeletal muscle
      as reported for rodents in response to fasting. Furthermore, UCP3 mRNA seems to
      be coregulated with PDK4 mRNA, indicating a relation to enhanced lipid
      metabolism. In contrast, UCP2 gene expression was not regulated in response to
      fasting in adipose tissue and skeletal muscle but was diminished in the lung and
      increased in adipose tissue. Taken together, the sequence analysis, tissue
      specificity and physiological regulation suggest a conserved function of UCP2 and
      UCP3 during 130 million years of mammalian evolution.

PMID- 14970362
TI  - Screening anti-inflammatory compounds in injured spinal cord with microarrays: a
      comparison of bioinformatics analysis approaches.
AB  - Inflammatory responses contribute to secondary tissue damage following spinal
      cord injury (SCI). A potent anti-inflammatory glucocorticoid, methylprednisolone
      (MP), is the only currently accepted therapy for acute SCI but its efficacy has
      been questioned. To search for additional anti-inflammatory compounds, we
      combined microarray analysis with an explanted spinal cord slice culture injury
      model. We compared gene expression profiles after treatment with MP,
      acetaminophen, indomethacin, NS398, and combined cytokine inhibitors (IL-1ra and
      soluble TNFR). Multiple gene filtering methods and statistical clustering
      analyses were applied to the multi-dimensional data set and results were
      compared. Our analysis showed a consistent and unique gene expression profile
      associated with NS398, the selective cyclooxygenase-2 (COX-2) inhibitor, in which
      the overall effect of these upregulated genes could be interpreted as
      neuroprotective. In vivo testing demonstrated that NS398 reduced lesion volumes,
      unlike MP or acetaminophen, consistent with a predicted physiological effect in
      spinal cord. Combining explanted spinal cultures, microarrays, and flexible
      clustering algorithms allows us to accelerate selection of compounds for in vivo
      testing.

PMID- 14970363
TI  - Tests of linkage and/or association of the LEPR gene polymorphisms with obesity
      phenotypes in Caucasian nuclear families.
AB  - Genetic variations in the leptin receptor (LEPR) gene have been conceived to
      affect body weight in general populations. In this study, using the tests
      implemented in the statistical package QTDT, we evaluated association and/or
      linkage of the LEPR gene with obesity phenotypes in a large sample comprising
      1,873 subjects from 405 Caucasian nuclear families. Obesity phenotypes tested
      include body mass index (BMI), fat mass, percentage fat mass (PFM), and lean
      mass, with the latter three measured by dual-energy X-ray absorptiometry (DXA).
      Three single nucleotide polymorphisms (SNPs), namely Lys109Arg (A/G), Lys656Asn
      (G/C), Pro1019Pro (G/A), in the LEPR gene were analyzed. Significant linkage
      disequilibrium (0.394 < or = |D'| < or = 0.688, P < 0.001) was observed between
      pairs of the three SNPs. No significant population stratification was found for
      any SNP/phenotype. In single-locus analyses, evidence of association was observed
      for Lys656Asn with lean mass (P = 0.002) and fat mass (P = 0.015). The
      contribution of this polymorphism to the phenotypic variation of lean mass and
      fat mass was 2.63% and 1.15%, respectively. Subjects carrying allele G at the
      Lys656Asn site had, on average, 3.16% higher lean mass and 2.71% higher fat mass
      than those without it. In the analyses for haplotypes defined by the three SNPs,
      significant associations were detected between haplotype GCA (P = 0.005) and lean
      mass. In addition, marginally significant evidence of association was observed
      for this haplotype with fat mass (P = 0.012). No statistically significant
      linkage was found, largely due to the limited power of the linkage approach to
      detect small genetic effects in our data sets. Our results suggest that the LEPR
      gene polymorphisms contribute to variation in obesity phenotypes.

PMID- 14970364
TI  - Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and
      mirtazapine.
AB  - OBJECTIVE: To report a case of serotonin syndrome (SS) resulting from the
      addition of tramadol to a medication regimen of venlafaxine and mirtazapine. CASE
      SUMMARY: A 47-year-old white man receiving combined mirtazapine and venlafaxine
      therapy for major depressive disorder developed agitation, confusion, severe
      shivering, diaphoresis, myoclonus, hyperreflexia, mydriasis, tachycardia, and
      fever on coadministration of tramadol for chronic pain. An objective causality
      assessment revealed that the addition of tramadol was the probable cause of the
      adverse reaction. DISCUSSION: SS is a potentially fatal iatrogenic complication
      of serotonergic polypharmacy. Considered idiopathic in presentation, it typically
      appears after initiation or dose escalation of the offending agent to a regimen
      including other serotonergic agents. All drugs that directly or indirectly
      increase central serotonin neurotransmission at postsynaptic 5-HT(1A) and 5
      HT(2A) receptors can produce SS. Individual vulnerability appears to play a role
      in the development of SS. It is likely that the activation of 5-HT(1A) receptors
      by mirtazapine, the combined serotonin reuptake inhibition by venlafaxine and
      tramadol, as well as possible serotonin release by tramadol, contributed to the
      development of SS in this case. CONCLUSIONS: It is vital that clinicians are
      aware of the potential for SS when psychotropic and nonpsychotropic agents are
      coadministered to certain patients, such as those with both depression and
      chronic pain.

PMID- 14970365
TI  - Hypocalcemia and azotemia associated with zoledronic acid and interferon alfa.
AB  - OBJECTIVE: To describe severe hypocalcemia and acute renal failure associated
      with zoledronic acid and interferon alfa in a patient with metastatic carcinoid
      tumors. CASE SUMMARY: A 39-year-old white man with metastatic carcinoid tumor
      tolerated treatment with subcutaneous long-acting octreotide monthly and
      interferon alfa 6 million units 3 times weekly for 6 months. Due to multiple bony
      metastases, zoledronic acid was prescribed as a monthly 4-mg intravenous infusion
      over 30 minutes to prevent skeletal-related events. Although the first infusion
      went well, the patient developed severe hypocalcemia and acute renal failure
      after the second zoledronic infusion. DISCUSSION: Bisphosphonates may
      infrequently cause symptomatic hypocalcemia, especially among patients who have
      vitamin D deficiency or hypoparathyroidism or receive treatment with an
      aminoglycoside. Our literature review suggests that zoledronic acid and
      interferon alfa may exert additive effects on the inhibition of osteoclasts, thus
      potentially precipitating hypocalcemia. Renal dysfunction may not be a direct
      consequence of interferon alfa. However, altered mental function due to
      hypocalcemia may lead to dehydration and further exacerbate renal dysfunction, a
      known adverse effect of zoledronic acid. Since therapeutic indications of both
      interferon alfa and zoledronic acid continue to expand, clinicians should be
      aware of these serious adverse reactions and potential interaction. Supportive
      treatment with hydration, calcium supplement, and oral calcitriol resulted in
      resolution of hypocalcemia, but only partial improvement of azotemia.
      CONCLUSIONS: In our patient with metastatic carcinoid tumor, treatment with
      zoledronic acid and interferon alfa was associated with symptomatic hypocalcemia
      and acute renal failure.

PMID- 14970366
TI  - Optimal management of methotrexate intoxication in a child with osteosarcoma.
AB  - OBJECTIVE: To describe the time course and management of methotrexate (MTX)
      toxicity in a 14-year-old Hispanic boy with osteosarcoma treated with high-dose
      MTX. CASE SUMMARY: During the sixth cycle of high-dose MTX, severe intoxication
      was observed with high MTX plasma concentrations, acute renal failure, and
      hepatitis, followed by mucositis and moderate myelosuppression. Intensification
      of urine alkalinization and increased leucovorin dosages did not decrease plasma
      concentrations of MTX or prevent systemic toxicities. Carboxypeptidase G2 and
      aminophylline were thus administered as a second-intention rescue strategy.
      Within 2 weeks, a recovery of clinical symptoms and normalization of the
      biological abnormalities were observed. Limb salvage surgery was performed, which
      permitted classifying the patient as an MTX high-responder. Thereafter, MTX was
      successfully resumed, leading to clinical recovery of the patient. Concomitantly,
      homocysteine plasma levels, a marker of the pharmacodynamic effect of MTX, were
      measured. During the intoxication, homocysteine plasma levels were significantly
      increased, parallel to the excessive MTX plasma concentrations observed.
      DISCUSSION: According to the excessive MTX levels measured in this patient, along
      with the observed clinical (mucositis) and biological (hepatitis, renal injury)
      adverse effects, we suggest that MTX may be a cause of these complications. Use
      of the Naranjo probability scale indicated a probable relationship between the
      complications and MTX. CONCLUSIONS: This observation shows that severe
      complications observed during one cycle of high-dose MTX is not predictive of the
      tolerability of further courses. Optimal management of such complications, using
      specific therapeutic intervention, may be considered.

PMID- 14970367
TI  - Single-dose azithromycin for respiratory tract infections.
AB  - OBJECTIVE: To describe the pharmacology, efficacy, and safety data of the use of
      single-dose azithromycin for respiratory tract infections in children and adults.
      DATA SOURCES: A MEDLINE search (1990-September 2003) was performed to identify
      all pertinent studies and review articles. When appropriate information was not
      available in the literature, data were obtained from the product manufacturers or
      abstracts from international conferences. STUDY SELECTION AND DATA EXTRACTION:
      All available studies were reviewed to provide pharmacokinetic, pharmacodynamic,
      efficacy, and safety data on use of single-dose azithromycin for respiratory
      tract infections. DATA SYNTHESIS: Several studies have demonstrated that shorter
      regimens of azithromycin (1500 mg over 3 day vs 5 day or single dose vs 3 day)
      provide higher serum exposures compared with the longer regimens. This makes it
      possible to give the same dose over a shorter period of time and achieve the same
      efficacy with the potential for enhanced adherence. Single-dose azithromycin 30
      mg/kg was approved in 2003 for treatment of acute otitis media (AOM) in children.
      Studies have demonstrated that, when administering azithromycin as a single dose,
      its efficacy and safety are comparable to that of other standard regimens for
      AOM. Single-dose regimens for treatment of respiratory tract infections in adults
      have not been studied widely, with only 2 studies being conducted for treatment
      of community-acquired pneumonia and one study for treatment of tonsillitis; all
      demonstrated at least equal efficacy with the single-dose regimen compared with
      comparators given for longer periods of time. CONCLUSIONS: Available data
      regarding single-dose azithromycin are promising. Although use of this regimen in
      children is warranted based on studies to date, additional large-scale trials are
      needed prior to mainstream use of the regimen in adults.

PMID- 14970368
TI  - Once-daily cefazolin and probenecid for skin and soft tissue infections.
AB  - OBJECTIVE: To review the pharmacokinetic and clinical evidence for the use of
      once-daily cefazolin and probenecid in the treatment of skin and soft tissue
      infections (SSTI). DATA SOURCES: MEDLINE (1966-July 2003), EMBASE (1980-July
      2003), and PubMed (1966-July 2003) databases for English language, human reports
      were searched. Search terms included cefazolin, probenecid, cellulitis, and soft
      tissue infections. STUDY SELECTION AND DATA EXTRACTION: Studies that described
      pharmacokinetic and clinical outcomes that evaluated the use of cefazolin in
      conjunction with probenecid for SSTI were included. All studies were evaluated
      independently by both authors. For pharmacokinetic studies, the effect of
      probenecid on the pharmacokinetics of cefazolin was evaluated. For clinical
      trials, efficacy and safety endpoints were evaluated. For efficacy endpoints,
      definition of cure was used as defined by each trial. DATA SYNTHESIS: In all 3
      pharmacokinetic studies identified, the addition of probenecid to cefazolin
      therapy prolonged the half-life and increased serum concentrations of cefazolin.
      This process allowed serum concentrations to be above the minimal inhibitory
      concentrations (MIC) for the most likely skin pathogens (Staphylococcus aureus,
      beta-hemolytic streptococci) at the end of the dosing interval. In the first of 2
      clinical trials, 7 (7%) of 96 patients receiving intravenous ceftriaxone 2 g and
      oral probenecid 1 g daily were reported to fail therapy compared with 8 (8%) of
      98 patients receiving intravenous cefazolin 2 g and oral probenecid 1 g daily. In
      the second clinical trial, clinical success was reported in 51 (86%) of 59
      patients receiving the same doses of cefazolin and probenecid as above compared
      with 55 (96%) of 57 patients receiving intravenous ceftriaxone 1 g and oral
      placebo daily. CONCLUSIONS: Limited pharmacokinetic and clinical data suggest
      that intravenous cefazolin 2 g and oral probenecid 1 g daily is an effective
      regimen in the treatment of SSTI.

PMID- 14970369
TI  - Role of corticosteroids in septic shock.
AB  - OBJECTIVE: To highlight the role of relative adrenal insufficiency in the outcome
      of critically ill patients with sepsis and systematically review the literature
      regarding the use of corticosteroids for management of severe sepsis/septic
      shock. DATA SOURCES: A computerized search of MEDLINE, EMBASE, and the Cochrane
      Database was undertaken from 1966 to March 2003 using the search terms intensive
      care unit, critical care, corticosteroids, glucocorticoids, adrenal
      insufficiency, sepsis, and septic shock. Bibliographies of all articles retrieved
      were searched for relevant articles not identified by the computerized search.
      DATA EXTRACTION/SYNTHESIS: Six trials were identified after publication of the
      meta-analyses (1995), with a total of 505 patients. The results of these trials
      in septic shock suggest that low-dose corticosteroids can reduce vasopressor
      requirements and hasten reversal of shock. Some of these trials suggested a
      possible mortality benefit from therapy, and no trial demonstrated an increase in
      mortality or significant adverse effects. The benefit of this therapy may depend
      on the presence of relative adrenal insufficiency, as identified by the
      adrenocorticotropic hormone stimulation test. CONCLUSIONS: Low-dose
      corticosteroids should be administered to patients with septic shock empirically,
      but should be discontinued if relative adrenal insufficiency is not confirmed.

PMID- 14970370
TI  - Anticonvulsant and antiretroviral interactions.
AB  - OBJECTIVE: To evaluate the clinical significance of interactions between
      anticonvulsant and antiretroviral agents and provide recommendations regarding
      their concurrent use. DATA SOURCES: A PubMed search (1966 to April 2003) was
      conducted using individual anticonvulsant and antiretroviral drug names and the
      following key search terms: anticonvulsant, antiepileptic, antiretroviral,
      protease inhibitor, and pharmacokinetic. Abstracts from scientific meetings that
      pertained to drug interactions were manually reviewed. STUDY SELECTION AND DATA
      EXTRACTION: All articles identified by the PubMed search were examined. Articles
      and abstracts from scientific meetings with relevant information were included.
      DATA SYNTHESIS: Six case reports were identified that describe interactions
      between anticonvulsant agents and protease inhibitors. In several reports,
      carbamazepine serum concentrations increased by approximately two- to threefold
      with concurrent ritonavir, resulting in carbamazepine-related toxicity.
      Carbamazepine was also associated with loss of viral suppression when combined
      with indinavir. Phenytoin serum concentrations were decreased with nelfinavir in
      a patient who developed recurrent seizures. The effect of ritonavir on phenytoin
      was variable; a 30% reduction in phenytoin serum concentration occurred in one
      patient, while no apparent change was observed in another. Interactions with
      nonnucleoside reverse-transcriptase inhibitors are poorly characterized because
      existing data involve concurrent protease inhibitor therapy. The utility of newer
      anticonvulsant agents is explored. Experience with newer anticonvulsant agents in
      2 patients at our site is also described. CONCLUSIONS: Limited data exist
      regarding interactions between anticonvulsant and antiretroviral agents. Valproic
      acid and newer anticonvulsant agents may provide useful alternatives to first
      generation agents. Clinicians need to be diligent when monitoring for
      anticonvulsant-antiretroviral interactions because of the potential for toxicity,
      loss of seizure control, and incomplete viral suppression.

PMID- 14970371
TI  - Management of asymptomatic bacteriuria in patients with diabetes mellitus.
AB  - OBJECTIVE: To review the literature regarding the management of asymptomatic
      bacteriuria (ASB) in patients with diabetes mellitus. DATA SOURCES: A MEDLINE
      (1967-June 2003) and bibliographic search of the English-language literature was
      conducted using the search terms diabetes mellitus, asymptomatic, bacteriuria,
      and urinary tract infection. DATA SYNTHESIS: ASB occurs in diabetic women more
      commonly than in non-diabetics and is associated with an increased risk of
      symptomatic urinary tract infection (UTI) among patients with type 2 diabetes.
      Symptomatic UTIs tend to follow a more complicated course in diabetics. Despite
      these independent observations, antimicrobial therapy has not been shown to
      reduce symptomatic UTIs, pyelonephritis, or hospitalization for UTI. CONCLUSIONS:
      Available evidence does not support antimicrobial treatment of ASB among patients
      with diabetes mellitus.

PMID- 14970372
TI  - Isotretinoin in the treatment of granuloma annulare.
AB  - OBJECTIVE: To assess the utility and safety of isotretinoin in the treatment of
      granuloma annulare (GA). DATA SOURCES: Searches of MEDLINE (1966-January 2003),
      EMBASE (1989-January 2003), International Pharmaceutical Abstracts (1970-2002),
      and Allied and Complementary Medicine Database (1985-2002) were conducted. Key
      terms included granuloma annulare, isotretinoin, retinoids, and antioxidants.
      DATA SYNTHESIS: Isotretinoin may have proliferative and inhibitory effects on
      collagen synthesis that improve GA symptoms. Cases reporting use of isotretinoin
      in the treatment of GA were reviewed. Several reports detail the successful use
      of isotretinoin 0.5-1 mg/kg/day, primarily in the disseminated form of the
      disease. However, some patients required dosage decreases in response to drug
      related liver function test elevations, and 2 instances of drug failure were
      identified. CONCLUSIONS: Isotretinoin should be reserved for patients with
      disseminated or refractory GA. Potential serious adverse effects associated with
      its use require careful monitoring.

PMID- 14970373
TI  - Coadministration of phenelzine and methylphenidate for treatment-resistant
      depression.

PMID- 14970374
TI  - Acute encephalopathy induced by oxcarbazepine and furosemide.

PMID- 14970375
TI  - Choroidal detachment with topical latanoprost after glaucoma filtration surgery.

PMID- 14970376
TI  - TARGETing "when" and "where".
AB  - In Drosophila, the cyclic adenosine monophosphate (cAMP) pathway has been shown
      to be crucial for learning and memory, but whether this represents a
      developmental or a specific effect has not been resolved. Research with a new
      targeting system that allows both spatial and temporal control of gene expression
      shows that expression of rutabaga-encoded adenylyl cyclase, a component of the
      cAMP signaling pathway, in the mushroom bodies of adult flies is necessary and
      sufficient to rescue the learning defect of rutabaga mutant. This demonstrates an
      acute role for Rutabaga in learning and memory.

PMID- 14970377
TI  - Spatiotemporal gene expression targeting with the TARGET and gene-switch systems
      in Drosophila.
AB  - Targeted gene expression has become a standard technique for the study of
      biological questions in Drosophila. Until recently, transgene expression could be
      targeted in the dimension of either time or space, but not both. Several new
      systems have recently been developed to direct transgene expression
      simultaneously in both time and space. We describe here two such systems that we
      developed in our laboratory. The first system provides a general method for
      temporal and regional gene expression targeting (TARGET) with the conventional
      GAL4-upstream activator sequence (UAS) system and a temperature-sensitive GAL80
      molecule, which represses GAL4 transcriptional activity at permissive
      temperatures. The second system, termed Gene-Switch, is based on a GAL4
      progesterone receptor chimera that is hormone-inducible. We have used both
      systems for simultaneous spatial and temporal rescue of memory dysfunction in the
      rutabaga (rut) memory mutant of Drosophila. In this protocol, we provide
      guidelines for the use of these two novel systems, which should have general
      utility in studying Drosophila biology and in using the fly as a model for human
      disease.

PMID- 14970378
TI  - A guide to ions and RNA structure.
AB  - RNA folding into stable tertiary structures is remarkably sensitive to the
      concentrations and types of cations present; an understanding of the physical
      basis of ion-RNA interactions is therefore a prerequisite for a quantitative
      accounting of RNA stability. This article summarizes the energetic factors that
      must be considered when ions interact with two different RNA environments.
      "Diffuse ions" accumulate near the RNA because of the RNA electrostatic field and
      remain largely hydrated. A "chelated" ion directly contacts a specific location
      on the RNA surface and is held in place by electrostatic forces. Energetic costs
      of ion chelation include displacement of some of the waters of hydration by the
      RNA surface and repulsion of diffuse ions. Methods are discussed for computing
      both the free energy of the set of diffuse ions associated with an RNA and the
      binding free energies of individual chelated ions. Such calculations
      quantitatively account for the effects of Mg(2+) on RNA stability where
      experimental data are available. An important conclusion is that diffuse ions are
      a major factor in the stabilization of RNA tertiary structures.

PMID- 14970379
TI  - The tRNA world.

PMID- 14970380
TI  - The Noc proteins involved in ribosome synthesis and export contain divergent HEAT
      repeats.
AB  - The Noc1-4p proteins were previously reported to be involved in intranuclear and
      nucleocytoplasmic transport of pre-ribosomes. Using fold recognition and
      structural modeling, we show that Noc1-4p are largely comprised of alpha-helical
      repeats similar to HEAT repeats. Because other HEAT-repeat proteins play key
      roles in transport processes, this finding provides a plausible mechanistic
      explanation for the function of the Noc proteins.

PMID- 14970381
TI  - Prediction of RNA-binding proteins from primary sequence by a support vector
      machine approach.
AB  - Elucidation of the interaction of proteins with different molecules is of
      significance in the understanding of cellular processes. Computational methods
      have been developed for the prediction of protein-protein interactions. But
      insufficient attention has been paid to the prediction of protein-RNA
      interactions, which play central roles in regulating gene expression and certain
      RNA-mediated enzymatic processes. This work explored the use of a machine
      learning method, support vector machines (SVM), for the prediction of RNA-binding
      proteins directly from their primary sequence. Based on the knowledge of known
      RNA-binding and non-RNA-binding proteins, an SVM system was trained to recognize
      RNA-binding proteins. A total of 4011 RNA-binding and 9781 non-RNA-binding
      proteins was used to train and test the SVM classification system, and an
      independent set of 447 RNA-binding and 4881 non-RNA-binding proteins was used to
      evaluate the classification accuracy. Testing results using this independent
      evaluation set show a prediction accuracy of 94.1%, 79.3%, and 94.1% for rRNA-,
      mRNA-, and tRNA-binding proteins, and 98.7%, 96.5%, and 99.9% for non-rRNA-, non
      mRNA-, and non-tRNA-binding proteins, respectively. The SVM classification system
      was further tested on a small class of snRNA-binding proteins with only 60
      available sequences. The prediction accuracy is 40.0% and 99.9% for snRNA-binding
      and non-snRNA-binding proteins, indicating a need for a sufficient number of
      proteins to train SVM. The SVM classification systems trained in this work were
      added to our Web-based protein functional classification software SVMProt, at
      http://jing.cz3.nus.edu.sg/cgi-bin/svmprot.cgi. Our study suggests the potential
      of SVM as a useful tool for facilitating the prediction of protein-RNA
      interactions.

PMID- 14970382
TI  - Internal loop mutations in the ribosomal protein L30 binding site of the yeast
      L30 RNA transcript.
AB  - Yeast ribosomal protein L30 binds to an asymmetric, purine-rich internal loop in
      its transcript to repress its own splicing and translation. The protein-bound
      form of the stem-internal loop-stem RNA is an example of a kink-turn RNA
      structural motif. Analysis of kink-turn motifs reveals that in (2 + 5) internal
      loops, the identities of five nucleotides are very important, while the remaining
      two may be varied. Previous SELEX experiments on the L30 binding site showed an
      identical pattern of sequence variation with five nucleotides highly conserved
      and two positions variable. In this work, internal loop residues were mutated and
      tested for protein binding in vitro and in vivo. The two sheared G-A pairs, which
      cannot be mutated without severely weakening L30 binding, make sequence specific
      contacts with other portions of the RNA and L30 protein. In contrast, the lone
      nucleotide that protrudes into the protein and an unpaired adenosine make no
      sequence-specific contacts, and may be mutated without compromising L30 binding.
      The internal loop allows the formation of a very tight bend that brings the two
      stems together with cross-strand stacking of two adenines and an interhelical
      ribose contact. Replacement of a ribonucleotide with a deoxynucleotide adjacent
      to the internal loop weakens protein binding significantly. In the absence of
      L30, some of the internal loop residues involved in the formation of the kink
      turn motif are protected from chemical modification, indicating that some
      elements of kink-turn structure may form in the free L30 RNA.

PMID- 14970383
TI  - Nascent-peptide-mediated ribosome stalling at a stop codon induces mRNA cleavage
      resulting in nonstop mRNA that is recognized by tmRNA.
AB  - Recent studies have established that tmRNA-mediated protein tagging occurs at
      stop codons depending on the C-terminal amino acid sequence of the nascent
      polypeptide immediately adjacent to those codons. We investigate here how the
      trans-translation at a stop codon occurs by using model crp genes encoding
      variants of cAMP receptor protein (CRP). We demonstrate that a truncated crp mRNA
      is efficiently produced along with a normal transcript from the model gene where
      tmRNA-mediated protein tagging occurs. The truncated crp mRNA was not detected in
      the presence of tmRNA, indicating that its degradation was facilitated by tmRNA.
      The major 3'-ends of the truncated crp mRNA in cells unable to express tmRNA were
      mapped at and near the stop codon. When RNA derived from the model crp-crr fusion
      gene was analyzed, crr mRNA was detected as a downstream cleavage product along
      with the upstream crp mRNA. These results are compatible with the hypothesis that
      ribosome stalling caused by the tagging-provoking sequences leads to
      endonucleolytic cleavage of mRNA around the stop codon, resulting in nonstop
      mRNA. In addition, the data are consistent with the view that mRNA cleavage is
      the cause of trans-translation at stop codons. Neither the bacterial toxin RelE
      nor the known major endoribonucleases are required for this cleavage, indicating
      that either other endoribonuclease(s) or the ribosome itself would be responsible
      for the mRNA cleavage in response to ribosome stalling caused by the particular
      nascent peptides.

PMID- 14970384
TI  - miRNP:mRNA association in polyribosomes in a human neuronal cell line.
AB  - MicroRNAs (miRNAs) are small regulatory RNAs that control gene expression by base
      pairing with their mRNA targets. miRNAs assemble into ribonucleoprotein complexes
      termed miRNPs. Animal miRNAs recognize their mRNA targets via partial antisense
      complementarity and repress mRNA translation at a step after translation
      initiation. How animal miRNAs recognize their mRNA targets and how they control
      their translation is unknown. Here we describe that in a human neuronal cell
      line, the miRNP proteins eIF2C2 (a member of the Argonaute family of proteins),
      Gemin3, and Gemin4 along with miRNAs cosediment with polyribosomes. Furthermore,
      we describe a physical association between a let-7b (miRNA)-containing miRNP and
      its putative human mRNA target in polyribosome-containing fractions. These
      findings suggest that miRNP proteins may play important roles in target mRNA
      recognition and translational repression.

PMID- 14970385
TI  - Modifications and deletions of helices within the hairpin ribozyme-substrate
      complex: an active ribozyme lacking helix 1.
AB  - Within the hairpin ribozyme, structural elements required for formation of the
      active tertiary structure are localized in two independently folding domains,
      each consisting of an internal loop flanked by helical elements. Here, we present
      results of a systematic examination of the relationship between the structure of
      the helical elements and the ability of the RNA to form the catalytically active
      tertiary structure. Deletions and mutational analyses indicate that helix 1 (H1)
      in domain A can be entirely eliminated, while segments of helices 2, 3, and 4 can
      also be deleted. From these results, we derive a new active minimal ribozyme that
      contains three helical elements, an internal loop, and a terminal loop. A three
      dimensional model of this truncated ribozyme was generated using MC-SYM, and
      confirms that the catalytic core of the minimized construct can adopt a tertiary
      structure that is very similar to that of the nontruncated version. A new
      strategy is described to study the functional importance of various residues and
      chemical groups and to identify specific interdomain interactions. This approach
      uses two physically separated and truncated domains derived from the minimal
      motif.

PMID- 14970386
TI  - Secondary structure of two regions in expansion segments ES3 and ES6 with the
      potential of forming a tertiary interaction in eukaryotic 40S ribosomal subunits.
AB  - The 18S rRNA of the small eukaryotic ribosomal subunit contains several expansion
      segments. Electron microscopy data indicate that two of the largest expansion
      segments are juxtaposed in intact 40S subunits, and data from phylogenetic
      sequence comparisons indicate that these two expansion segments contain
      complementary sequences that could form a direct tertiary interaction on the
      ribosome. We have investigated the secondary structure of the two expansion
      segments in the region around the putative tertiary interaction. Ribosomes from
      yeast, wheat, and mouse-three organisms representing separate eukaryotic kingdoms
      were isolated, and the structure of ES3 and part of the ES6 region were analyzed
      using the single-strand-specific chemical reagents CMCT and DMS and the double
      strand-specific ribonuclease V1. The modification patterns were analyzed by
      primer extension and gel electrophoresis on an ABI 377 automated DNA sequencer.
      The investigated sequences were relatively exposed to chemical and enzymatic
      modification. This is in line with their indicated location on the surface at the
      solvent side of the subunit. The complementary ES3 and ES6 sequences were clearly
      inaccessible to single-strand modification, but available for cleavage by double
      strand-specific RNase V1. The results are compatible with a direct helical
      interaction between bases in ES3 and ES6. Almost identical results were obtained
      with ribosomes from the three organisms investigated.

PMID- 14970387
TI  - Evidence for a base triple in the free HIV-1 TAR RNA.
AB  - We propose the existence of a novel base triple in the HIV-1 TAR hairpin. This
      triple is supported by covariation of loop residue 31 with residue 22, which is
      part of an unusual base pair with U40 below the 3-nucleotide bulge. A set of
      mutants was constructed to test the involvement of bases A22, U31, and U40 in a
      triple interaction. RNA structure probing, trans-activation assays, and structure
      modeling are consistent with the existence of this base triple in a bent
      conformation of the free TAR element. However, disruption of the base triple does
      not affect binding of a Tat-derived peptide. We therefore compared the structure
      of free and Tat-bound TAR RNA by footprinting and site-specific cross-linking
      analyses. These studies indicate that the Tat arginine-rich motif, in addition to
      its known binding site at the bulge, is in close contact with U31 in the TAR
      loop. Because binding of Tat to TAR is known to coincide with the formation of a
      base triple with residues U23, A27, and U38, we hypothesize that Tat binding and
      the associated straightening of TAR triggers the disruption of the (A22-U40)U31
      triple.

PMID- 14970388
TI  - Secondary structure and function of the 5'-proximal region of the equine
      arteritis virus RNA genome.
AB  - Nidoviruses produce an extensive 3'-coterminal nested set of subgenomic mRNAs,
      which are used to express their structural proteins. In addition, arterivirus and
      coronavirus mRNAs contain a common 5' leader sequence, derived from the genomic
      5' end. The joining of this leader sequence to different segments (mRNA bodies)
      from the genomic 3'-proximal region presumably involves a unique mechanism of
      discontinuous minus-strand RNA synthesis. Key elements in this process are the so
      called transcription-regulating sequences (TRSs), which determine a base-pairing
      interaction between sense and antisense viral RNA that is essential for leader-to
      body joining. To identify RNA structures in the 5'-proximal region of the equine
      arteritis virus genome that may be involved in subgenomic mRNA synthesis, a
      detailed secondary RNA structure model was established using bioinformatics,
      phylogenetic analysis, and RNA structure probing. According to this structure
      model, the leader TRS is located in the loop of a prominent hairpin (leader TRS
      hairpin; LTH). The importance of the LTH was supported by the results of a
      mutagenesis study using an EAV molecular clone. Besides evidence for a direct
      role of the LTH in subgenomic RNA synthesis, indications for a role of the LTH
      region in genome replication and/or translation were obtained. Similar LTH
      structures could be predicted for the 5'-proximal region of all arterivirus
      genomes and, interestingly, also for most coronaviruses. Thus, we postulate that
      the LTH is a key structural element in the discontinuous subgenomic RNA synthesis
      and is likely critical for leader TRS function.

PMID- 14970389
TI  - Intracellular expression of engineered RNase P ribozymes effectively blocks gene
      expression and replication of human cytomegalovirus.
AB  - A ribozyme (M1GS RNA) constructed from the catalytic RNA subunit of RNase P from
      Escherichia coli was used to target the overlapping region of two human
      cytomegalovirus (HCMV) mRNAs, which encode for the viral essential protease (PR)
      and capsid assembly proteins (AP), respectively. The results show a reduction of
      >80% in the expression levels of PR and AP and an inhibition of approximately
      2000-fold of viral growth in cells that stably expressed the ribozyme. In
      comparison, <10% reduction in the expression of the targets and viral growth was
      found in cells that either did not express the ribozyme or produced a "disabled"
      ribozyme carrying mutations that abolished its catalytic activity. Examination of
      replication of the virus in the ribozyme-expressing cells indicates that
      packaging of the viral genomic DNA into capsids is blocked, and suggests that the
      antiviral effects are because the ribozyme specifically inhibits the AP and PR
      expression and, consequently, abolishes viral capsid formation and growth. Our
      results show that RNase P ribozymes are highly effective in blocking HCMV growth
      by targeting the PR and AP mRNAs and demonstrate the feasibility to use these
      ribozymes in gene therapy for antiviral applications.

PMID- 14970390
TI  - Characterization of deadenylation in trypanosome extracts and its inhibition by
      poly(A)-binding protein Pab1p.
AB  - The stability of mRNAs is an important point in the regulation of gene expression
      in eukaryotes. The mRNA turnover pathways have been identified in yeast and
      mammals. However, mRNA turnover pathways in trypanosomes have not been widely
      studied. Deadenylation is the first step in the major mRNA turnover pathways of
      yeast and mammals. To better understand mRNA degradation processes in these
      organisms, we have developed an in vitro mRNA turnover system that is functional
      for deadenylation. In this system, addition of poly(A) homopolymer activates the
      deadenylation of poly(A) tails. The trypanosomal deadenylase activity is a 3'-
      >5' exonuclease specific for adenylate residues, generates 5'-AMP as a product,
      is magnesium dependent, and is inhibited by neomycin B sulfate. These
      characteristics suggest similarity with other eukaryotic deadenylases.
      Furthermore, this activity is cap independent, indicating a potential difference
      between the trypanosomal activity and PARN, but suggesting similarity to
      Ccr4p/Pop2p activities. Extracts immunodepleted of Pab1p required the addition of
      poly(A) competition to activate deadenylation. Trypanosomal Pab1p functions as an
      inhibitor of the activity under in vitro conditions. Pab1p appears to be one of
      several mRNA stability proteins in trypanosomal extracts.

PMID- 14970391
TI  - Inhibition of 5' to 3' mRNA degradation under stress conditions in Saccharomyces
      cerevisiae: from GCN4 to MET16.
AB  - After deadenylation, most cytoplasmic mRNAs are decapped and digested by 5' to 3'
      exonucleases in Saccharomyces cerevisiae. Capped and deadenylated mRNAs are
      degraded to a lesser extent by 3' to 5' exonucleases. We have used a method,
      based on the electroporation of in vitro synthetised mRNAs, to study the relative
      importance of these two exonucleolytic pathways under stress conditions. We show
      that derepression of GCN4 upon amino acid starvation specifically limits the 5'
      to-3'-degradation pathway. Because adenosine 3'-5' biphosphate (pAp), which is
      produced by Met16p, inhibits this degradation pathway to a comparable extent, we
      were prompted to analyse the role of Met16p in this phenomenon. We show that the
      inhibitory effects of amino acid limitation on 5' to 3' mRNA degradation are
      absent in a met16 mutant. We therefore conclude that the GCN4 dependence of MET16
      expression is responsible for the decrease in 5' to 3' digestion under stress
      conditions and that cells use pAp as a signal to limit 5' to 3' RNA degradation
      under stress conditions. Because 3' to 5' mRNA degradation is unaffected, the
      relative importance of this pathway in the decay of certain RNAs may be increased
      under stress conditions.

PMID- 14970392
TI  - Translation of cellular inhibitor of apoptosis protein 1 (c-IAP1) mRNA is IRES
      mediated and regulated during cell stress.
AB  - Cellular inhibitor of apoptosis protein 1 (c-IAP1) can regulate apoptosis through
      its interaction with downstream TNF receptor effectors (TRAF1 and TRAF2), by
      binding to and inhibiting certain caspases, and by controlling the levels of
      specific proapoptotic stimuli (e.g., Smac/DIABLO) within the cell. Studies
      involving the expression of c-IAP1 mRNA and protein in cells and tissues have
      provided evidence suggesting c-IAP1 expression may be posttranscriptionally
      controlled. Because the 5'-UTR of c-IAP1 mRNA is unusually long, contains
      multiple upstream AUG codons, and has the potential to form thermodynamically
      stable secondary structures, we investigated the possibility it contained an
      internal ribosome entry site (IRES) that may regulate its expression. In the
      present study, the c-IAP1 5'-UTR exhibited IRES activity when dicistronic RNA
      constructs were translated in rabbit reticulocyte lysate (RRL) and in transiently
      transfected cells. IRES-mediated translation was similar to that exhibited by the
      hepatitis C virus IRES but varied significantly in RRL and in HeLa, HepG2, and
      293T cells, indicating the c-IAP1 IRES was system and cell type specific. IRES
      mediated translation was maintained in mono- and dicistronic constructs in which
      the UTR was inserted downstream from a stable hairpin that prevented cap
      dependent ribosome scanning. In cells, the presence or absence of a methylated
      cap did not significantly affect the translation of polyadenylated, monocistronic
      RNAs containing the c-IAP1 5'-UTR. IRES-mediated translation was stimulated in
      transfected cells treated with low doses of pro-apoptotic stimuli (i.e.,
      etoposide and sodium arsenite) that inhibited endogenous cellular translation.

PMID- 14970393
TI  - Interaction of the Bacillus subtilis RNase P with the 30S ribosomal subunit.
AB  - Ribonuclease P (RNase P) is a ribozyme required for the 5' maturation of all
      tRNA. RNase P and the ribosome are the only known ribozymes conserved in all
      organisms. We set out to determine whether this ribonucleoprotein enzyme
      interacts with other cellular components, which may imply other functions for
      this conserved ribozyme. Incubation of the Bacillus subtilis RNase P holoenzyme
      with fractionated B. subtilis cellular extracts and purified ribosomal subunits
      results in the formation of a gel-shifted complex with the 30S ribosomal subunit
      at a binding affinity of approximately 40 nM in 0.1 M NH(4)Cl and 10 mM MgCl(2).
      The complex does not form with the RNase P RNA alone and is disrupted by a mRNA
      mimic polyuridine, but is stable in the presence of high concentrations of mature
      tRNA. Endogenous RNase P can also be detected in the 30S ribosomal fraction.
      Cleavage of a pre-tRNA substrate by the RNase P holoenzyme remains the same in
      the presence of the 30S ribosome, but the cleavage of an artificial non-tRNA
      substrate is inhibited eightfold. Hydroxyl radical protection and chemical
      modification identify several protected residues located in a highly conserved
      region in the RNase P RNA. A single mutation within this region significantly
      reduces binding, providing strong support on the specificity of the RNase P-30S
      ribosome complex. Our results also suggest that the dimeric form of the RNase P
      is primarily involved in 30S ribosome binding. We discuss several models on a
      potential function of the RNase P-30S ribosome complex.

PMID- 14970394
TI  - Functional group recognition at the aminoacylation and editing sites of E. coli
      valyl-tRNA synthetase.
AB  - To correct misactivation and misacylation errors, Escherichia coli valyl-tRNA
      synthetase (ValRS) catalyzes a tRNA(Val)-dependent editing reaction at a site
      distinct from its aminoacylation site. Here we examined the effects of replacing
      the conserved 3'-adenosine of tRNA(Val) with nucleoside analogs, to identify
      structural elements of the 3'-terminal nucleoside necessary for tRNA function at
      the aminoacylation and editing sites of ValRS. The results show that the
      exocyclic amino group (N6) is not essential: purine riboside-substituted
      tRNA(Val) is active in aminoacylation and in stimulating editing. Presence of an
      O6 substituent (guanosine, inosine, xanthosine) interferes with aminoacylation as
      well as posttransfer and total editing (pre- plus posttransfer editing). Because
      ValRS does not recognize substituents at the 6-position, these results suggest
      that an unprotonated N1, capable of acting as an H-bond acceptor, is an essential
      determinant for both the aminoacylation and editing reactions. Substituents at
      the 2-position of the purine ring, either a 2-amino group (2-aminopurine, 2,6
      diaminopurine, guanosine, and 7-deazaguanosine) or a 2-keto group (xanthosine,
      isoguanosine), strongly inhibit both aminoacylation and editing. Although
      aminoacylation by ValRS is at the 2'-OH, substitution of the 3'-terminal
      adenosine of tRNA(Val) with 3'-deoxyadenosine reduces the efficiency of valine
      acceptance and of posttransfer editing, demonstrating that the 3'-terminal
      hydroxyl group contributes to tRNA recognition at both the aminoacylation and
      editing sites. Our results show a strong correlation between the amino acid
      accepting activity of tRNA and its ability to stimulate editing, suggesting
      misacylated tRNA is a transient intermediate in the editing reaction, and editing
      by ValRS requires a posttransfer step.

PMID- 14970395
TI  - Characterization of two distinct RNA domains that regulate translation of the
      Drosophila gypsy retroelement.
AB  - The genomic RNA of the gypsy retroelement from Drosophila melanogaster exhibits
      features similar to other retroviral RNAs because its 5' untranslated (5' UTR)
      region is unusually long (846 nucleotides) and potentially highly structured. Our
      initial aim was to search for an internal ribosome entry site (IRES) element in
      the 5' UTR of the gypsy genomic RNA by using various monocistronic and
      bicistronic RNAs in the rabbit reticulocyte lysate (RRL) system and in cultured
      cells. Results reported here show that two functionally distinct and independent
      RNA domains control the production of gypsy encoded proteins. The first domain
      corresponds to the 5' UTR of the env subgenomic RNA and exhibits features of an
      efficient IRES (IRES(E)) both in the reticulocyte lysate and in cells. The second
      RNA domain that encompasses the gypsy insulator can function as an IRES in the
      rabbit reticulocyte lysate but strongly represses translation in cultured cells.
      Taken together, these results suggest that expression of the gypsy encoded
      proteins from the genomic and subgenomic RNAs can be regulated at the level of
      translation.

PMID- 14970396
TI  - Biostable aptamers with antagonistic properties to the neuropeptide
      nociceptin/orphanin FQ.
AB  - The neuropeptide nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the
      opioid receptor-like 1 (ORL1) receptor, has been shown to play a prominent role
      in the regulation of several biological functions such as pain and stress. Here
      we describe the isolation and characterization of N/OFQ binding biostable RNA
      aptamers (Spiegelmers) using a mirror-image in vitro selection approach.
      Spiegelmers are L-enantiomeric oligonucleotide ligands that display high affinity
      and specificity to their targets and high resistance to enzymatic degradation
      compared to D-oligonucleotides. A representative Spiegelmer from the selections
      performed was size-minimized to two distinct sequences capable of high affinity
      binding to N/OFQ. The Spiegelmers were shown to antagonize binding of N/OFQ to
      the ORL1 receptor in a binding-competition assay. The calculated IC(50) values
      for the Spiegelmers NOX 2149 and NOX 2137a/b were 110 nM and 330 nM,
      respectively. The competitive antagonistic properties of these Spiegelmers were
      further demonstrated by their effective and specific inhibition of G-protein
      activation in two additional models. The Spiegelmers antagonized the N/OFQ
      induced GTPgammaS incorporation into cell membranes of a CHO-K1 cell line
      expressing the human ORL1 receptor. In oocytes from Xenopus laevis, NOX 2149
      showed an antagonistic effect to the N/OFQ-ORL 1 receptor system that was
      functionally coupled with G-protein-regulated inwardly rectifying K(+) channels.

PMID- 14970397
TI  - Eukaryotic protein synthesis inhibitors identified by comparison of cytotoxicity
      profiles.
AB  - The National Cancer Institute (NCI) Human Tumor Cell Line Anti-Cancer Drug Screen
      has evaluated the cytotoxicity profiles of a large number of synthetic compounds,
      natural products, and plant extracts on 60 different cell lines. The data for
      each compound/extract can be assessed for similarity of cytotoxicity pattern,
      relative to a given test compound, using an algorithm called COMPARE. In applying
      a chemical biology approach to better understand the mechanism of eukaryotic
      protein synthesis, we used these resources to search for novel inhibitors of
      translation. The cytotoxicity profiles of 31 known protein synthesis inhibitors
      were used to identify compounds from the NCI database with similar activity
      profiles. Using this approach, two natural products, phyllanthoside and
      nagilactone C, were identified and characterized as novel protein synthesis
      inhibitors. Both compounds are specific for the eukaryotic translation apparatus,
      function in vivo and in vitro, and interfere with translation elongation. Our
      results demonstrate the feasibility of utilizing cytotoxicity profiles to
      identify new inhibitors of translation.

PMID- 14970398
TI  - Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing.
AB  - A large number of miRNAs have recently been discovered in plants and animals.
      Development of reverse genetic approaches that act to inhibit microRNA function
      would facilitate the study of this new class of noncoding RNA. Here we show that
      2'-O-methyl oligoribonucleotides, but not 2'-deoxyoligonucleotides specifically
      inactivate the RNAi activity associated with miRNA-protein complexes in human
      cell extracts as well as in cultured human cells.

PMID- 14970399
TI  - Factors influencing the beliefs of patients with rheumatoid arthritis regarding
      disease-modifying medication.
AB  - OBJECTIVE: To investigate factors influencing the beliefs of patients with
      rheumatoid arthritis (RA) regarding disease-modifying medication. METHOD: Twenty
      nine patients with RA either starting a disease-modifying anti-rheumatic drug
      (DMARD) for the first time or changing DMARD were recruited. Semi-structured
      interviews, activity diaries and focus groups were conducted over 9 months. A
      coding framework was developed and data analysed using the constant comparative
      method to identify key themes. RESULTS: DMARDs were perceived as central to the
      management of RA but strong concerns were expressed about potential long-term
      effects. Beliefs about DMARDs were informed by material from a wide range of
      sources. Judgements of efficacy were influenced by symptom relief, occurrence of
      side-effects and perception of alternative treatment options. Perception,
      reporting and tolerance of side-effects differed widely between individuals. The
      emotional impact of starting and being withdrawn from medication appeared
      stronger in people with more experience of DMARD use. CONCLUSIONS: Patients have
      complex and evolving belief systems relating to DMARDs. Understanding these
      systems will facilitate the provision of appropriate information and effective
      support not only in decision-making about treatment but also in relation to
      discontinuing treatment.

PMID- 14970400
TI  - Clinical utility of anti-CCP antibodies in the differential diagnosis of elderly
      onset rheumatoid arthritis and polymyalgia rheumatica.
AB  - BACKGROUND: In a significant number of patients the differential diagnosis
      between elderly-onset rheumatoid arthritis (EORA) and polymyalgia rheumatica
      (PMR) is very difficult because of the lack of specific serum markers. Anti
      cyclic citrullinated peptide antibodies (anti-CCP Abs) have recently been shown
      to be highly specific for rheumatoid arthritis (RA). This is the first study
      addressing the utility of these antibodies in the differential diagnosis between
      EORA and PMR. METHODS: Serum samples from 57 EORA patients and 49 PMR patients
      were studied for the presence of anti-CCP Abs and rheumatoid factor (RF). As
      controls, samples from 41 RA patients (age at onset <60 yr) and 24 aged healthy
      subjects were analysed. RESULTS: Sixty-five per cent of EORA patients had anti
      CCP Abs, whereas none of the PMR patients or the aged healthy subjects was
      positive for those antibodies. Ten of the EORA patients started with polymyalgic
      symptoms and two of them were positive for anti-CCP Abs. Interestingly, there was
      a significant correlation between anti-CCP Abs and RF in EORA but not in young RA
      patients. CONCLUSIONS: The presence of anti-CCP Abs in a patient with clinical
      symptoms of PMR must be interpreted as highly suggestive of EORA.

PMID- 14970402
TI  - From natural to artificial chromosomes: an overview.

PMID- 14970401
TI  - Up-regulation of XCR1 expression in rheumatoid joints.
AB  - OBJECTIVES: Chemokine receptor-positive cells play a crucial role in controlling
      synovitis in rheumatoid arthritis (RA). We studied 16 chemokine receptors of the
      CC, CXC, CX3C and C families by analysing venous blood and synovial fluid samples
      and synovial tissues from RA patients. METHODS: Mononuclear cells (MNCs) in
      paired synovial fluid and venous blood samples from 7 RA patients were studied
      for the expression of CCR1 to 9, CXCR1 to 5, CX3CR1 and XCR1 by quantitative
      reverse transcription polymerase chain reaction (RT-PCR). Expression of chemokine
      receptors on synovial tissues from 9 RA patients were examined by in situ
      hybridization. Levels of chemokines were measured by enzyme-linked immunosorbant
      assay. RESULTS: Higher expression levels of XCR1 and CCR5 in MNCs from synovial
      fluid, as compared with those from venous blood, were consistently demonstrated
      in all RA patients (P<0.01). Through in situ hybridization, XCR1 expression was
      detected in infiltrating MNCs and synoviocytes in synovial tissues. Levels of
      lymphotactin, the ligand of XCR1, were significantly higher in the joint fluid
      than those in the paired serum samples (P<0.01). CONCLUSIONS: We found an up
      regulation of XCR1 expression in MNCs from the rheumatoid joint, and detected
      XCR1 expression in infiltrating MNCs in synovial tissues, as well as increased
      lymphotactin levels in synovial fluid. XCR1-positive cells may play a role in
      rheumatoid joints.

PMID- 14970403
TI  - Methodologies applied to domestic animal chromosomes.

PMID- 14970404
TI  - Mapping of the hotspots of recombination in human DNA cloned as yeast artificial
      chromosomes.

PMID- 14970405
TI  - Genomic imprinting and its effects on genes and chromosomes in mammals.

PMID- 14970406
TI  - Centromeres and neocentromeres.

PMID- 14970407
TI  - Identification of start sites of bi-directional DNA synthesis at eukaryotic DNA
      replication origins.

PMID- 14970408
TI  - Telomere length analysis and in vitro telomerase assay.

PMID- 14970409
TI  - Telomerization of mammalian cells and transplantation of telomerized cells in
      immunodeficient mice.

PMID- 14970410
TI  - Chromosome-based vectors for Mammalian cells: an overview.

PMID- 14970411
TI  - Mammalian artificial chromosome formation in human cells after lipofection of a
      PAC precursor.

PMID- 14970412
TI  - Use of natural and artificial chromosome vectors for animal transgenesis.

PMID- 14970413
TI  - Pronuclear microinjection of purified artificial chromosomes for generation of
      transgenic mice: pick-and-inject technique.

PMID- 14970414
TI  - Modification of human bacterial artificial chromosome clones for functional
      studies and therapeutic applications.

PMID- 14970434
TI  - Processing of resorbable poly-alpha-hydroxy acids for use as tissue-engineering
      scaffolds.

PMID- 14970435
TI  - Fibrin microbeads (FMB) as biodegradable carriers for culturing cells and for
      accelerating wound healing.

PMID- 14970436
TI  - Synthesis and characterization of hyaluronan-based polymers for tissue
      engineering.

PMID- 14970437
TI  - Synthesis and characterization of chitosan scaffolds for cartilage-tissue
      engineering.

PMID- 14970438
TI  - Characterization of a calcium phosphate-based matrix for rhBMP-2.

PMID- 14970439
TI  - Methodologies for processing biodegradable and natural origin scaffolds for bone
      and cartilage tissue-engineering applications.

PMID- 14970440
TI  - Alginates in tissue engineering.

PMID- 14970441
TI  - Production and surface modification of polylactide-based polymeric scaffolds for
      soft-tissue engineering.

PMID- 14970442
TI  - Modification of materials with bioactive peptides.

PMID- 14970443
TI  - Isolation and osteogenic differentiation of bone-marrow progenitor cells for
      application in tissue engineering.

PMID- 14970444
TI  - Cell seeding of polymer scaffolds.

PMID- 14970445
TI  - Chondrocyte isolation, expansion, and culture on polymer scaffolds.

PMID- 14970446
TI  - Bioreactor culture techniques for cartilage-tissue engineering.

PMID- 14970447
TI  - Microscopic methods for the analysis of engineered tissues.

PMID- 14970448
TI  - Transmission electron microscopy of tissue-polymer constructs.

PMID- 14970449
TI  - Application of microscopic methods for the detection of cell attachment to
      polymers.

PMID- 14970450
TI  - Biochemical methods for the analysis of tissue-engineered cartilage.

PMID- 14970451
TI  - Real-time quantitative rt-PCR assays.

PMID- 14970452
TI  - Mechanical testing of cell-material constructs: a review.

PMID- 14970453
TI  - Technical considerations in quantitating gene expression.

PMID- 14970454
TI  - Gene expression quantitation technology summary.
AB  - Scientists routinely talk and write about gene expression and the abundance of
      transcripts, but in reality they extrapolate this information from the various
      measurements that a variety of different technologies provide. Indeed, there are
      many reasons why applying different technologies to the problem of transcript
      abundance may give different results, owing to an incomplete understanding of the
      gene in question or from shortcomings in the applications of the technologies.
      There are nine basic considerations for making a technology choice for
      quantitating gene expression that will impact the overall outcome: architecture,
      specificity, sensitivity, sample requirement, coverage, throughput, cost,
      reproducibility, and data management. These considerations will be discussed in
      the context of available technologies.

PMID- 14970455
TI  - Standardized RT-PCR and the standardized expression measurement center.
AB  - Standardized reverse transcriptase polymerase chain reaction (StaRT-PCR) is a
      modification of the competitive template (CT) RT method described by Gilliland et
      al. StaRT-PCR allows rapid, reproducible, standardized, quantitative measurement
      of data for many genes simultaneously. An internal standard CT is prepared for
      each gene, cloned to generate enough for 10(9) assays and CTs for up to 1,000
      genes are mixed together. Each target gene is normalized to a reference gene to
      control for cDNA loaded in a standardized mixture of internal standards (SMIS)
      into the reaction. Each target gene and reference gene is measured relative to
      its respective internal standard within the SMIS. Because each target gene and
      reference gene is simultaneously measured relative to a known number of internal
      standard molecules in the SMIS, it is possible to report each gene expression
      measurement as a numerical value in units of target gene cDNA molecules/ 10(6)
      reference gene cDNA molecules. Calculation of data in this format allows for
      entry into a common databank, direct interexperimental comparison, and
      combination of values into interactive gene expression indices.

PMID- 14970456
TI  - GeneCalling: transcript profiling coupled to a gene database query.
AB  - We describe the GeneCalling method for the discovery of differentially expressed
      genes, both known and novel, from any species including useful sequence
      information to determine the potential function of novel genes captured. The
      method relies on transcript visualization coupled to a database query to rapidly
      and quantitatively identify differentially expressed transcripts. The method has
      been applied to a wide variety of disease models in a variety of species,
      addressing problems as diverse as identifying novel human cancer gene targets,
      understanding how drugs and diet affect animal models of disease, and
      understanding the basis of trait differences in related strains of corn.

PMID- 14970457
TI  - Invader assay for RNA quantitation.
AB  - The Invader assay is a homogeneous, isothermal, signal amplification system for
      the quantitative detection of nucleic acids. The assay can directly detect either
      DNA or RNA without target amplification or reverse transcription. It is based on
      the ability of Cleavase enzymes to recognize as a substrate and cleave a specific
      nucleic acid structure generated through the hybridization of two
      oligonucleotides to the target sequence. The combination of sequence-specific
      oligonucleotide hybridization and structure-specific enzymatic cleavage results
      in a highly specific assay well suited for discriminating closely related gene
      sequences. This includes detection of single nucleotide polymorphisms directly
      from genomic DNA as well as highly homologous mRNAs in closely related gene
      families. Because Cleavase substrate recognition is structure, and not sequence
      dependent, cleavage and detection can be applied to virtually any DNA or RNA
      sequence.

PMID- 14970458
TI  - Monitoring eukaryotic gene expression using oligonucleotide microarrays.
AB  - An increasing number of biological and medical research questions depend on
      obtaining global views of gene expression. In this chapter, we will describe how
      oligonucleotide microarrays have been used to accomplish this goal. In
      particular, we will focus on the use of GeneChip arrays, which provide high
      levels of reproducibility, sensitivity, and specificity. Target preparation,
      hybridization, washing, signal detection, and data analysis will be described in
      detail. Additionally, we will discuss options for facilitating data sharing,
      including the creation of databases, and the use of internet tools that help
      users place their results in the context of data from public and proprietary
      databases. There is so much interest and innovation in the field of genomics that
      protocols are constantly evolving. This chapter should be used as a genomic
      profiling guide only. We urge readers to consult www.affymetrix.com for the most
      current products and protocols.

PMID- 14970459
TI  - Amplified differential gene expression microarray.
AB  - Amplified Differential Gene Expression (ADGE) and DNA microarray provides a new
      concept that the ratios of differentially expressed genes are magnified prior to
      detecting them. The ratio magnification is achieved with the integration of DNA
      reassociation and polymerase chain reaction (PCR) amplification and ensured with
      the design of the adapters and primers. The ADGE technique can be used either as
      a stand-alone method or in series with DNA microarray. ADGE is used in sample
      preprocessing and DNA microarray is used as a displaying system in the series
      combination. The combination of ADGE and DNA microarray provides a mutual
      complement of their strengths: the magnification of ratios of differential gene
      expression improves the detection sensitivity; the PCR amplification and
      efficient labeling enhance the signal intensity and reduce the requirement for
      large amounts of starting material; and the high throughput for DNA microarray is
      maintained.

PMID- 14970460
TI  - Suppression subtractive hybridization.
AB  - Suppression subtractive hybridization (SSH) is a widely used method for
      separating DNA molecules that distinguish two closely related DNA samples. Two of
      the main SSH applications are cDNA subtraction and genomic DNA subtraction. In
      fact, SSH is one of the most powerful and popular methods for generating
      subtracted cDNA or genomic DNA libraries. The SSH method is based on a
      suppression PCR effect and combines normalization and subtraction in a single
      procedure. The normalization step equalizes the abundance of DNA fragments within
      the target population, and the subtraction step excludes sequences that are
      common to the populations being compared. This dramatically increases the
      probability of obtaining low-abundance differentially expressed cDNA or genomic
      DNA fragments, and simplifies analysis of the subtracted library. In our hands,
      the SSH technique has enriched over 1000-fold for rare sequences in a single
      round of subtractive hybridization.

PMID- 14970461
TI  - Small amplified RNA-SAGE.
AB  - Serial analysis of gene expression (SAGE) is a powerful genome-wide analytic tool
      to determine expression profiles. Since its description in 1995 by Victor
      Velculescu et al., SAGE has been widely used. Recently, the efficiency of the
      method has been emphasized as a means to identify novel transcripts or genes that
      are difficult to identify by conventional methods. SAGE is based on the principle
      that a 10-base pair (bp) cDNA fragment contains sufficient information to
      unambiguously identify a transcript, provided it is isolated from a defined
      position within this transcript. Concatenation of these sequence tags allows
      serial analysis of transcripts by sequencing multiple tags within a single clone.
      Extraction of sequence data by computer programs provides a list of sequence tags
      that reflect both qualitatively and quantitatively the gene expression profile.
      Several modifications to the initial protocol allowed to start from 1 microg
      total RNA (or 10(5) cells). In order to reduce the amount of input RNA, protocols
      including extra polymerase chain reaction (PCR) steps were designed. Linear
      amplification of the mRNA targets might have advantage over PCR by minimizing
      biases introduced by the amplification step; therefore we devised a SAGE protocol
      in which a loop of linear amplification of RNA has been included. Our approach,
      named "small amplified RNA-SAGE" (SAR-SAGE) included a T7 RNA polymerase promoter
      within an adapter derived from the standard SAGE linker. This allowed
      transcription of cDNA segments, extending from the last NlaIII site of
      transcripts to the polyA tail; these small amplified RNAs then serve as template
      in a classical (micro)SAGE procedure. As the cDNAs are immobilized on oligo(dT)
      magnetic beads, several rounds of transcription can be performed in succession
      with the same cDNA preparation, with the potential to increase further the yield
      in a linear way. Except for the transcription step itself, the present procedure
      does not introduce any extra enzymatic reaction in the classical SAGE protocol,
      it is expected to keep the representation biases associated with amplification as
      low as possible.

PMID- 14970462
TI  - Gene expression informatics.
AB  - There are many methodologies for performing gene expression profiling on
      transcripts, and through their use scientists have been generating vast amounts
      of experimental data. Turning the raw experimental data into meaningful
      biological observation requires a number of processing steps; to remove noise, to
      identify the "true" expression value, normalize the data, compare it to reference
      data, and to extract patterns, or obtain insight into the underlying biology of
      the samples being measured. In this chapter we give a brief overview of how the
      raw data is processed, provide details on several data-mining methods, and
      discuss the future direction of expression informatics.

PMID- 14970489
TI  - The Kabat database and a bioinformatics example.

PMID- 14970490
TI  - IMGT, The International ImMunoGeneTics Information System, http://imgt.cines.fr.

PMID- 14970491
TI  - Antibody variable regions: toward a unified modeling method.

PMID- 14970492
TI  - Studying antibody conformations by ultracentrifugation and hydrodynamic modeling.

PMID- 14970493
TI  - PCR cloning of human immunoglobulin genes.

PMID- 14970494
TI  - Antibody humanization by CDR grafting.

PMID- 14970495
TI  - Selection of human antibodies from phage display libraries.

PMID- 14970496
TI  - Production of human single-chain antibodies by ribosome display.

PMID- 14970497
TI  - Production of human antibodies from transgenic mice.

PMID- 14970498
TI  - Selection of internalizing antibodies for drug delivery.

PMID- 14970499
TI  - Engineering multivalent antibody fragments for in vivo targeting.

PMID- 14970500
TI  - Production of recombinant bispecific antibodies.

PMID- 14970501
TI  - Expression and isolation of recombinant antibody fragments in E. coli.

PMID- 14970502
TI  - Expression of recombinant antibodies in mammalian cell lines.

PMID- 14970503
TI  - Human antibody production using insect-cell expression systems.

PMID- 14970504
TI  - Antibody production in transgenic plants.

PMID- 14970505
TI  - Directed mutagenesis of antibody variable domains.

PMID- 14970506
TI  - Antibody affinity maturation by chain shuffling.

PMID- 14970507
TI  - Antibody affinity maturation by random mutagenesis.

PMID- 14970508
TI  - Developing a minimally immunogenic humanized antibody by SDR grafting.

PMID- 14970509
TI  - Antibody purification by column chromatography.

PMID- 14970510
TI  - Affinity measurement using surface plasmon resonance.

PMID- 14970511
TI  - Kinetic exclusion assays to study high-affinity binding interactions in
      homogeneous solutions.

PMID- 14970512
TI  - Characterization of antibody-antigen interactions by fluorescence spectroscopy.

PMID- 14970513
TI  - Antibody epitope mapping using arrays of synthetic peptides.

PMID- 14970514
TI  - Mapping antibody:antigen interactions by mass spectrometry and bioinformatics.

PMID- 14970515
TI  - Radiometal labeling of antibodies and antibody fragments for imaging and therapy.

PMID- 14970516
TI  - Production and characterization of anti-cocaine catalytic antibodies.

PMID- 14970517
TI  - Recombinant immunotoxins in the treatment of cancer.

PMID- 14970518
TI  - Antibodies in proteomics.

PMID- 14970519
TI  - Targeting of antibodies using aptamers.

PMID- 14970537
TI  - General strategies.

PMID- 14970538
TI  - Preparation of extracts from animal tissues.

PMID- 14970539
TI  - Protein extraction from plant tissues.

PMID- 14970540
TI  - Extraction of recombinant protein from bacteria.

PMID- 14970541
TI  - Protein extraction from fungi.

PMID- 14970542
TI  - Subecllular fractionation of animal tissues.

PMID- 14970543
TI  - Subcellular fractionation of plant tissues: isolation of plastids and
      mitochondria.

PMID- 14970544
TI  - The extraction of enzymes from plant tissues rich in phenolic compounds.

PMID- 14970545
TI  - Avoidance of proteolysis in extracts.

PMID- 14970546
TI  - Concentration of extracts.

PMID- 14970547
TI  - Making and changing buffers.

PMID- 14970548
TI  - Purification and concentration by ultrafiltration.

PMID- 14970549
TI  - Bulk purification by fractional precipitation.

PMID- 14970550
TI  - Ion-exchange chromatography.

PMID- 14970551
TI  - Hydrophobic interaction chromatography.

PMID- 14970552
TI  - Affinity chromatography.

PMID- 14970553
TI  - Dye-ligand affinity chromatography.

PMID- 14970554
TI  - Lectin affinity chromatography.

PMID- 14970555
TI  - Immunoaffinity chromatography.

PMID- 14970556
TI  - Immobilized metal-ion affinity chromatography.

PMID- 14970557
TI  - Chromatography on hydroxyapatite.

PMID- 14970558
TI  - Thiophilic affinity chromatography and related methods.

PMID- 14970559
TI  - Affinity precipitation methods.

PMID- 14970560
TI  - Isoelectric focusing.

PMID- 14970561
TI  - Chromatofocusing.

PMID- 14970562
TI  - Size-exclusion chromatography.

PMID- 14970563
TI  - Fast protein liquid chromatography.

PMID- 14970564
TI  - Reversed-phase chromatography of proteins.

PMID- 14970565
TI  - Extraction of membrane proteins.

PMID- 14970566
TI  - Removal of detergent from protein fractions.

PMID- 14970567
TI  - Purification of membrane proteins.

PMID- 14970568
TI  - Lyophilization of proteins.

PMID- 14970569
TI  - Storage of pure proteins.

PMID- 14970570
TI  - Electroelution of proteins from polyacrylamide gels.

PMID- 14970571
TI  - Electroblotting of proteins from polyacrylamide gels.

PMID- 14970572
TI  - Two-dimensional polyacrylamide gel electrophoresis for proteome analyses.

PMID- 14970573
TI  - Microscale solution isoelectrofocusing: a sample prefractionation method for
      comprehensive proteome analysis.

PMID- 14970574
TI  - Practical column chromatography.

PMID- 14970575
TI  - Detection methods.

PMID- 14970576
TI  - Peptide proteomics.

PMID- 14970577
TI  - Multidimensional liquid chromatography of proteins.

PMID- 14970578
TI  - Mass spectrometry.

PMID- 14970579
TI  - Purification of therapeutic proteins.

PMID- 14970580
TI  - Purification process scale-up.

PMID- 14970581
TI  - Adenovirus-mediated gene delivery: an overview.
AB  - Adenoviruses, which were first isolated in the 1950s, have been developed as gene
      delivery vehicles, or vectors, since the early 1980s. The adenoviruses constitute
      the Adenoviridae family, which is divided into two genera: the Aviadenovirus
      genus infects only birds, whereas the Mastadenovirus genus contains viruses that
      infect a range of mammalian species. Human adenoviruses are classified into six
      subgroups based on the percentage of guanine and cytosine in the DNA molecules
      and the ability to agglutinate red blood cells. They are further subdivided into
      more than 50 serotypes, primarily on the basis of neutralization assays.

PMID- 14970582
TI  - DNA delivery to cells in culture: generation of adenoviral libraries for high
      throughput functional screening.
AB  - In functional genomics, the use of expression libraries of DNA variants in
      combination with potent screening techniques is a powerful tool for gene
      discovery. They allow study of gene and protein function, generation of peptide
      variants with novel properties, as well as identification of functional short DNA
      and RNA motifs. In proteomics, generation of large expression libraries of
      protein variants with random substitutions ("directed evolution") and further
      screening for novel or improved functions has been commonly used for isolation of
      proteins with novel characteristics, for improving enzymes, for rapid isolation
      of antibodies, and for functional protein studies. Most commonly, peptide
      libraries are expressed and screened in prokaryotic systems. Such systems have
      the advantage of rapid and simple generation of clones expressing single
      variants, allow high diversity (up to 10(11)), and can be combined with phage- or
      cell-surface display technique (2). The main disadvantage of bacterial systems is
      the absence of posttranslational modifications and native folding of many
      mammalian proteins, leading to limited applications, particularly when enzyme
      substrate-, protein-protein, or protein-RNA interactions are to be studied.

PMID- 14970583
TI  - Adenovirus-mediated gene delivery to skeletal muscle.
AB  - Adenoviral vectors can be employed for gene delivery to skeletal muscle, both ex
      vivo and in vivo. Although the realization of the full potential of adenoviral
      vectors awaits the development of methods to allow safe and efficient targeted
      gene delivery to mature skeletal muscle upon intravenous vector administration
      (1), the current generation of vectors has nonetheless found utility in
      preclinical studies of gene therapy and in gene-transfer experiments designed to
      study muscle biology. Features of adenoviral vectors that have favored their use
      for gene delivery to skeletal muscle include the ability to infect both actively
      dividing and terminally differentiated cells, as well as their large insert
      capacity. Gutted adenoviral vectors are capable of carrying the large dystrophin
      gene together with regulatory sequences, and are therefore appropriate vehicles
      for gene-replacement therapy for Duchenne muscular dystrophy. In addition to
      their suitability for in vivo gene-therapy applications, adenoviral vectors have
      been used ex vivo to transfer genes to myoblasts prior to myoblast
      transplantation into muscle.

PMID- 14970584
TI  - Delivery of adenoviral DNA to mouse liver.
AB  - The liver represents a major target organ for gene delivery owing to its high
      biosynthetic capacity and access to the bloodstream. Adenoviral vectors are
      highly efficient gene-transfer vehicles, making them among the most promising
      systems for in vivo gene transfer to the liver. Following intravenous
      administration of adenoviral vectors to a variety of mammalian models, including
      mice, dogs, and monkeys, hepatocytes are efficiently transduced. Several delivery
      methods to the liver have been described, including portal vein (2-4), hepatic
      artery (3,5), and peripheral vein infusions (6). This chapter describes the
      simple, nonsurgical method of intravenous (iv) administration of adenoviral
      vectors in mice, and an immunohistochemical method to qualitatively evaluate
      liver transduction efficiency following delivery of an adenoviral vector encoding
      a bgalactosidase (beta-gal) marker gene. Additionally, several alternative
      methods to verify efficient liver transduction are introduced.

PMID- 14970585
TI  - Delivery of DNA to lung airway epithelium.
AB  - Delivering exogenous DNA or genes directly to the lung airways offers a unique
      and appealing opportunity for specifically targeting gene expression to airway
      and alveolar epithelium. A large body of literature and experience supports the
      feasibility of this approach. However, airway-directed gene delivery is not as
      simple as was originally anticipated. The lung has evolved both physical and
      immunologic barriers that can hinder effective transduction of epithelial cells
      (1-3). Much current work in lung gene therapy is directed toward overcoming the
      inflammatory and immune responses provoked by gene-transfer vectors while
      simultaneously maximizing vector delivery and subsequent gene expression.

PMID- 14970586
TI  - Delivery of DNA to pulmonary endothelium using adenoviral vectors.
AB  - Delivery of genes to the pulmonary vascular endothelium is a rational approach
      for the investigation and potential therapy of pulmonary vascular diseases.
      Furthermore, in view of the exposure of this vascular bed to the entire cardiac
      output, this technique could be used as an efficient basis to achieve systemic
      delivery of secreted factors. The attraction of direct gene delivery to
      endothelium for the therapy of vascular disease has been especially heightened in
      the last couple of years in view of the new discoveries concerning the genetic
      basis of primary pulmonary hypertension (PPH). In brief, mutations in the bone
      morphogenetic protein receptor type 2 (BMPR2, a member of the transforming growth
      factor-beta [TGF-beta] family of receptors) gene have been found in many patients
      with familial PPH. Subsequent in vitro studies have confirmed an association
      between BMPR2 mutations and abnormal proliferative responses in pulmonary
      endothelial and smooth-muscle cells (2). Other TGF-beta signaling pathways may
      also be involved in this process, and the mechanisms involved may also have
      relevance for the more common cases of pulmonary vascular disease secondarily
      associated with chronic airways obstruction, connective tissue diseases, and
      perhaps HIV infection. Additionally, new evidence is emerging concerning the role
      of the vasculature in the pathogenesis of emphysema.

PMID- 14970587
TI  - Gene transfer to brain and spinal cord using recombinant adenoviral vectors.
AB  - Recombinant adenoviral (Ad) vectors are derived from human adenoviruses:
      nonenveloped, encapsidated linear, double-stranded DNA viruses that commonly
      cause respiratory and gastrointestinal infections. Forty-three different human
      adenovirus serotypes have been characterized. Details about production of
      recombinant Ad vectors are given in Chapter 1. Ad vectors in widespread use are
      derived from human Ad serotypes 2 and 5 (Ad2 and Ad5), Ad5 being more common for
      applications in the central nervous system (CNS). Ad5 replication-impaired
      vectors most often contain deletions in the E1 and E3 regions, with transgenes
      driven by a variety of promoters including viral promoters, and those that are
      neuron-specific (2). Recently fiber-modified and "gutless" Ad vectors, and those
      based on canine adenovirus serotype 2, have been developed for use in brain (3
      9).

PMID- 14970588
TI  - Adenovirus-mediated gene transfer to tumor cells.
AB  - Cell transduction in vitro is only the first step toward proving that a
      genetherapy vector can be useful to treat tumors. However, tumor targeting in
      vivo is now the milestone for gene therapy to succeed against disseminated
      cancer. Therefore, most valuable information is obtained from studies of vector
      biodistribution. Owing to the hepatotropism of adenoviral vectors, a particularly
      important parameter is the tumor/liver ratio. This ratio can be given at the
      level of gene expression if the amount of transgene expression is measured. To
      optimize the targeting, however, the levels of viral particles that reach the
      tumor compared to other organs must be studied. Most of this chapter deals with
      methods to quantify the virus fate in tumor-bearing animals. We present a
      radioactive labeling method that can be used to study biodistribution. After a
      small section dealing with tumor models, we describe methods to quantify
      different parameters related to adenovirus-mediated tumor targeting.

PMID- 14970589
TI  - Adenovirus-mediated gene delivery to dendritic cells.
AB  - Dendritic cells (DCs) are "professional" antigen-presenting cells (APCs) that are
      uniquely capable of activating and instructing a naive immune system to mount a
      specific cellular and humoral response. Recognition of this crucial function
      makes the development of technologies for DC-based immuno-therapies a priority
      for the treatment of a wide variety of diseases. The most immediate impact of
      this emerging technology will be in the treatment of cancer and the development
      of third generation vaccines to protect against viral and intracellular
      pathogens. In addition to elicitation of immune responses, DCs also function to
      maintain tolerance to "self." Once the biological basis for this important
      function is understood, future applications of DC-based immuotherapies may be
      developed to ameliorate autoimmune diseases or enhance acceptance of transplanted
      organs. The feasibility of "engineering" the function of DCs has been realized by
      recent advances in ex vivo methodologies that allow selective DC propagation,
      antigen loading, and genetic modification in vitro for subsequent therapeutic
      transfer into the host. Ultimately, the ability to genetically modify these cells
      will allow us to design DC-mediated interventions that will direct predictable
      control of either immune activation or tolerance in vivo.

PMID- 14970590
TI  - Overview of adeno-associated viral vectors.
AB  - The use of adeno-associated virus (AAV) as a gene transfer vector has been
      steadily increasing over the past several years. AAV vectors have been
      particularly useful for applications where sustained gene expression is required.
      Prolonged in vivo expression following AAV treatment has been seen in the liver
      (1,2), brain (3,4), skeletal muscle (5,6), lung (7,8), and hematopoietic stem
      cells (9,10) of animal models. Therapeutic benefit from AAV treatment has been
      shown in a number of preclinical models of disease, including animal models of
      coagulopathies (11,12), lysosomal storage diseases (13,14), vision defects
      (15,16), and amino acid disorders. Clinical trials using AAV for the treatment of
      hemophilia B have begun, and early reports from these trials have been promising.
      In this introductory chapter to AAV, we will provide a brief overview of the
      molecular biology of this virus, an overview of methods of vector production, and
      a brief summary of the use of alternate AAV serotypes. The following chapters
      will then focus on specific methods and techniques for AAV transduction of the
      organs listed previously.

PMID- 14970591
TI  - AAV vector delivery to cells in culture.
AB  - Adeno-associated virus (AAV) gene delivery vectors are being investigated as
      vehicles for gene therapy for a wide variety of hereditary and acquired human
      diseases. AAV's inability to self-propagate, ability to be maintained as an
      episome in the transduced cell, and relatively innocuous effects on the immune
      system make it the vector of choice for prolonged in vivo gene expression. AAV
      type 2 is the most commonly used serotype for gene delivery. AAV2 vectors will
      deliver DNA to a wide variety of cell types. The development of vectors derived
      from the other five serotypes has expanded the tissue tropism of the AAV vector
      system. Tropism depends on the presence of cell-surface receptor elements on the
      target cell. For AAV2, heparin sulfate proteoglycan (7), alpha2betaV integrin (8)
      and the fibroblast growth factor receptor-1 (FGFR-1) (9) are believed to mediate
      the initial internalization steps in infection. The ubiquity of these cell
      surface components confers a wide tropism on AAV2 vectors.

PMID- 14970592
TI  - AAV-mediated gene transfer to skeletal muscle.
AB  - Adeno-associated viral (AAV) vectors are derived from a nonpathogenic,
      replication-deficient virus with a small (~4.7-kb) single-stranded DNA genome.
      AAV vectors are devoid of viral-coding sequences and may efficiently transfer
      genes to nondividing cells such as muscle fibers or hepatocytes following in vivo
      transduction. Recombinant AAV can be administered to skeletal muscle of
      experimental animals and, as recently documented in a Phase I clinical trial, to
      humans at high vector doses without local or systemic toxicity (8,9). The
      potential of the vector to activate cytotoxic T lymphocytes is greatly reduced
      compared with some other viral vectors, thereby reducing the risk of inflammation
      at the site of gene transfer (7,10,11). Sustained expression of therapeutic
      transgenes such as coagulation factor IX (F.IX), erythropoietin, leptin, insulin
      like growth factor (IGF), sarcoglycans, mini-dystrophin genes, alpha1
      antitrypsin, and others have been demonstrated (2,12-18). Efficient gene transfer
      to myofibers by intramuscular (im) injection has been shown in several species
      including mice, hamsters, dogs, and nonhuman primates (6-8,13,19). These studies
      resulted in various levels of correction of the disease phenoypes in small and
      large animal models of hemophilia B (F.IX deficiency), muscular dystrophy,
      obesity, age-related atrophy, and beta-thalassemia (8,12,13,15,17,18,20-25).

PMID- 14970593
TI  - AAV-mediated gene transfer to the liver.
AB  - The liver is a frequent target of gene-transfer experiments, because of its
      central role in many metabolic and synthetic pathways. For applications where
      prolonged expression of genes in the liver is required, adeno-associated virus
      (AAV) has proven to be an effective tool for in vivo gene transfer. High-level,
      persistent hepatic expression has been achieved in a number of experimental
      systems following a single treatment with AAV in murine and larger animal models.
      This prolonged expression is particularly useful for the treatment of genetic
      diseases such as the inborn errors of metabolism, where lifelong expression of
      the deficient enzyme may be required. Therapeutic benefits using AAV vectors have
      been demonstrated in animal models of amino acid disorders, lysosomal storage
      diseases, and coagulopathies (3-5), and Phase I clinical trials are proposed for
      the treatment of hemophilia B (6). Gene transfer to the murine liver using AAV is
      achieved by intravenous (iv) injection of recombinant virus, either via a
      peripheral or portal vein. The liver is the primary organ transduced following
      intravenous injection of AAV, although other tissues such as heart and lung may
      also take up virus to a lesser extent when peripheral injection sites are used
      (7). Portal-vein injection can reduce the amount of extra-hepatic transduction,
      and allows a larger dose of virus to be delivered to the liver. However, this
      technique requires surgical expertise, and can only be performed on adult mice.

PMID- 14970594
TI  - AAV-mediated gene transfer to mouse lungs.
AB  - The ability of adeno-associated viral (AAV) vectors to promote persistent gene
      expression in nondividing cells in multiple somatic tissues of animals (1-4)
      makes them excellent tools for gene transfer. One tissue of interest for gene
      transfer is the lung epithelium, which is afflicted in cystic fibrosis (CF).
      However, although initial animal studies done with vectors based on AAV type 2
      have demonstrated transduction in multiple cells types in the lung, the rates
      were modest in alveolar cells and much lower rates in airway epitheila and
      required high particle numbers (5-7). In contrast, an AAV6 encapsidated vector
      showed preferential transduction of epithelial cells in large and small airways
      (8) at rates that exceeded the 5% efficiency rate predicted to have a therapeutic
      value for CF gene therapy (9). In fact, recent studies using vectors based on
      other AAV types showed that types 1-6 have different tissue tropisms (10-15), and
      that types 5 and 6 are more efficient than type 2 in lung epithelium (8,14). In
      mouse lung, an AAV2 vector gave modest transduction rates.

PMID- 14970595
TI  - Gene delivery to the mammalian heart using AAV vectors.
AB  - There are a large number of cardiovascular diseases that could be treated by
      myocardial gene transfer. These include congestive heart failure, ischemic heart
      disease, and cardiomyopathy. In addition to its potential for treatment of
      disease, myocardial gene transfer is useful for the analysis of gene expression
      and promoter function and for generating animal models of human disease such as
      pulmonary hypertension. The ideal vector for myocardial gene therapy should give
      efficient and stable transduction of cardiomyocytes in vivo. Recombinant
      adenovirus vectors have been used to transduce cardiomyocytes in rodents,
      rabbits, pigs, and humans by both intramyocardial injection and intracoronary
      infusion (3-5). Although efficient transduction can be obtained with adenovirus
      vectors, immune responses and elimination of transduced cells results in only
      transient expression in immunocompetent hosts. Vectors based on recombinant adeno
      associated virus (rAAV) offer a number of attractive features and are emerging as
      promising gene transfer vehicles for many in vivo applications.

PMID- 14970596
TI  - Gene delivery to the mouse brain with adeno-associated virus.
AB  - The efficient transduction of postmitotic cells by adeno-associated virus (AAV)
      makes it an excellent vector to deliver marker, functional, or therapeutic genes
      to the mammalian brain. An attractive feature of AAV is that all the viral-coding
      sequences are removed when engineering the recombinant genome, thereby limiting
      the extent of cell toxicity and immune response that are often associated with
      viral gene transcription. Of the seven described AAV serotypes, AAV serotype-2
      (AAV2) is the most studied gene-transfer vehicle for in the mammalian brain. A
      feature of AAV2 transduction in the brain is that the vector remains confined to
      the injection site and predominately infects neurons rather than glia (2-8). The
      limited diffusion of AAV2 vectors is beneficial for controlled gene delivery. For
      instance, targeting therapeutic genes only to brain structures showing pathology
      would eliminate complications associated with vector diffusion and subsequent
      expression in healthy structures, and is an important consideration when
      designing treatment strategies for localized neurodegenerative diseases. The same
      is true for other experimental paradigms, such as investigating the function of
      genes in specific brain structures or using marker genes in tract-tracing
      experiments. Although AAV2 vectors were shown to remain predominately at the
      injection site, one study demonstrated that the vector itself may undergo axonal
      transport in inter-regional systems (9).

PMID- 14970597
TI  - Delivery of DNA to tumor cells in vivo using adeno-associated virus.
AB  - The number of published studies on transduction of tumor cells in vivo using
      recombinant adeno-associated virus (rAAV) vectors is very limited compared with
      those that have been published on targeting normal cells. A major reason for this
      can be attributed to the biology of the vector itself. AAV, being a nonpathogenic
      vector capable of providing transgene integration and long-term expression, is
      ideally suited for the correction of metabolic defects either to replace a
      defective protein/enzyme or to elevate their otherwise suboptimal levels in the
      system. However, increased understanding of both the biology of tumor progression
      and potential utility of AAV-based vectors suggests that this vector can also be
      wisely used for cancer gene therapy.

PMID- 14970598
TI  - Gene delivery to human and murine primitive hematopoietic stem and progenitor
      cells by AAV2 vectors.
AB  - The adeno-associated virus 2 (AAV2) is known to possess a broad host-range that
      transcends the species barrier. The broad host-range and nonpathogenic nature of
      AAV, coupled with its site-specificity and stable integration of the proviral
      genome, have led to the development of recombinant AAV vectors (2). Recombinant
      AAV vectors have been shown to transduce certain cell types, such as muscle and
      brain, exceedingly well (3-5). However, controversies exist with regard to the
      efficacy of AAV vectors in transducing human hematopoietic stem cells (6).
      Whereas some investigators have concluded that AAV vectors do not transduce human
      hematopoietic cells at all (7), other reports have documented the need for
      enormously high multiplicities of infection (MOIs) by AAV vectors for successful
      transduction (8-13). Several groups, including my own, have reported successful
      transduction of these cells at relatively low MOIs (14-17). Some of these
      controversies have been addressed in a recent review article (18).

PMID- 14970599
TI  - Delivery using herpes simplex virus: an overview.
AB  - The human herpesviruses represent excellent candidate viruses for several types
      of gene vector applications. As a class, they are large DNA viruses with the
      potential to accommodate large or multiple transgene cassettes, and they have
      evolved to persist in a lifelong nonintegrated latent state without causing
      disease in the immune-competent host. Among the herpesviruses, herpes simplex
      virus type 1 (HSV-1) is an attractive vehicle because in natural infection, the
      virus establishes latency in neurons, a state in which viral genomes may persist
      for the life of the host as intranuclear episomal elements. The natural lifelong
      persistence of latent genomes in trigeminal ganglia (TG) without the development
      of sensory loss or histologic damage to the ganglion attests to the effectiveness
      of these natural latency mechanisms. Although the wild-type virus may be
      reactivated from latency under the influence of a variety of stresses, completely
      replication defective viruses can be constructed that retain the ability to
      establish persistent quiescent genomes in neurons, but that are unable to
      subsequently reactivate in the nervous system. These persistent genomes are
      devoid of lytic gene expression, but retain the ability to express latency
      associated transcripts (LATs).

PMID- 14970600
TI  - Gene transfer to skeletal muscle using herpes simplex virus-based vectors.
AB  - Type 1 herpes simplex virus (HSV-1)-based vectors, which are naturally capable of
      carrying large DNA fragments like the 14 kb dystrophin cDNA, have been studied
      for their ability to transduce muscle cells. These vectors can persist in the
      host cell in a nonintegrated state and can be prepared at adequately high titers
      (10(7)-10(9) PFU/mL). They also infect myoblasts, myotubes, and immature
      myofibers efficiently. The major disadvantage of the first-generation HSV vectors
      is their relatively high cytotoxicity, which hampers long-term transgene
      expression. Second-generation mutants defective for multiple immediate early (IE)
      genes (e.g., ICP4, ICP22, and ICP27) display substantially reduced cytotoxicity
      in vitro, which improves the duration of transgene expression (6-11). In this
      chapter, we describe a new method of gene delivery using second-generation HSV-1
      vectors. This procedure should enable an investigator to transduce normal mouse
      muscle cells, both in vitro and in vivo. We explain the conditions for muscle
      cell isolation, transduction in vitro and in vivo, and the technique for
      evaluating transduction efficiency (beta-galactosidase; beta-gal) using histology
      or the beta-gal assay (ONPG) method.

PMID- 14970601
TI  - Delivery of herpes simplex virus-based vectors to the nervous system.
AB  - Gene transfer to the nervous system is an attractive option to treat a wide
      variety of neurological insults. The expression of trophic factor and/or
      antiapoptotic genes may be beneficial in halting the slow neurodegeneration in
      such conditions as Parkinson's disease (4,5), the rapid neuronal cell death
      following trauma to the brain or spinal cord (6,7), or in treating peripheral
      neuropathies associated with diabetes or use of chemotherapeutic agents (8,9).
      Introduction of dominant-negative mutant genes or antisense RNA to treat diseases
      such as Huntington's disease, or transfer of genes to replace lost or mutated
      endogenous proteins to treat disorders such as lysosomal storage diseases, may
      prove useful. In addition, gene transfer to overexpress endogenous
      antinociceptive proteins has great potential in pain management. The problem
      faced by all of these applications is finding a suitable methodology that will
      facilitate the transfer of exogenous genes to the appropriate nerve cells;
      virusbased vectors have proven quite efficient in transferring genes to many
      different cell types.

PMID- 14970602
TI  - Gene transfer to glial tumors using herpes simplex virus.
AB  - Glial tumors occur as intraaxial masses in the brain and are uniformly fatal due
      to lack of effective therapy. Resection combined with radiation and chemotherapy
      fails to eradicate malignant cells infiltrating into normal brain, and recurrence
      at the original site is ultimately fatal. Gene transfer offers the potential to
      enhance tumor cell killing while sparing surrounding normal brain. Several
      approaches have been developed to deliver genes to tumor cells in order to kill
      these cells. The first strategy involves the use of viral vectors that are
      replication-competent, but depend on attributes unique to the tumor cell to
      support viral growth. Both replication-competent adenovirus and herpes simplex
      virus (HSV) vectors have been employed in pre-clinical studies and most recently
      in human clinical trials. For this purpose, HSV vectors have been engineered that
      replicate in dividing cells, such as tumor cells, but not in normal neurons. The
      use of conditional replication competent viruses could allow for their spread in
      tumor tissue while minimizing damage to normal brain, thus increasing the
      specificity and effectiveness. Such mutants include those lacking the viral
      thymidine kinase (tk) gene (4-7), ribonucleotide reductase gene (8,9), a protein
      kinase gene, or a gene (gamma34.5) required for growth specifically in neurons
      (11-13).

PMID- 14970603
TI  - Delivery of herpes simplex virus-based vectors to stem cells.
AB  - In contrast to traditional drugs that generally act by altering existing gene
      product function, gene therapy aims to target the root cause of the disease by
      altering the genetic makeup of the cell to treat the disease. Researchers have
      adapted several classes of viruses as gene-transfer vectors, taking advantage of
      natural viral mechanisms designed to efficiently and effectively deliver DNA to
      the host-cell nucleus. Among these, the human herpesviruses are excellent
      candidate vectors for a variety of applications. Herpes simplex virus type 1 (HSV
      1) is a particularly attractive gene-transfer vehicle because natural infection
      in humans includes a latent state in which the viral genome persists in a
      nonintegrated form without causing disease in an immune-competent host. HSV-1 is
      a large DNA virus with a broad host range that can be engineered to accommodate
      multiple or large therapeutic transgenes (4). HSV vectors may be generally useful
      for gene transfer to a variety of tissues in which short-term or extended
      transgene expression of therapeutic transgenes achieve a therapeutic effect. We
      have used therapeutic vectors to successfully treat human disease models in
      animals, including cancer, Parkinson's disease, and nerve damage (5-10).

PMID- 14970604
TI  - Baculovirus-mediated gene delivery into mammalian cells.
AB  - A relatively recent advance in the use of recombinant baculoviruses is their use
      for delivery of genes and genetic elements into mammalian cells. Baculovirus
      vectors retrofitted with mammalian gene promoters have been shown to efficiently
      deliver and express genes in a broad assortment of cell types. These baculovirus
      transductions are simple to perform, reproducible, and demonstrate no overt cell
      toxicity. Baculovirus-mediated gene delivery is particularly useful for
      repetitive or moderately high-throughput procedures such as cell-based assays, or
      for situations where transfection procedures are inadequate.

PMID- 14970605
TI  - Gene delivery by lentivirus vectors an overview.
AB  - For more than two decades, retroviral biology has been the most intensely studied
      field in virology. The retroviral genome is encoded by a 7-11 kb positivesense
      single-stranded RNA molecule, two of which homodimerize and package in lipid
      enveloped viral particles. Following attachment and receptor-mediated entry into
      host cells, viral reverse transcriptase and integrase enzymes mediate reverse
      transcription and integration of the virus genome into the host-cell chromatin.
      The ability of a replication competent retrovirus to incorporate a herpes simplex
      virus thymidine kinase (tk) gene into the genome of a mouse cell and to convert
      NIH-3T3 TK- cells into TK+ transformants was first described in 1981 (1,2). These
      studies established the basis of using retroviruses as vehicles for efficient
      therapeutic gene delivery into mammalian cells. Twenty years of extensive
      research of retrovirus-vector biology resulted in major improvements in vector
      design and retrovirus-vector production. High-titer concentrated retrovirus
      vectors (>10(9) infectious units [IU]/mL) can be generated by several
      retrovirusvector stable producer lines. The ability to pseudotype retrovirus
      vectors with a variety of envelope proteins, including the vesicular stomatitis
      virus G glycoprotein (VSV-G), significantly broadens the tropism of replication
      defective retrovirus vectors.

PMID- 14970606
TI  - Lentiviral vectors for the delivery of DNA into mammalian cells.
AB  - Vectors derived from oncoretroviruses, represented by the prototype Moloney
      murine leukemia virus (MMLV), are powerful tools for gene transfer into mammalian
      cells. Vectors derived from such viruses are able to carry an insert of up to 6.5
      kb. Because Retroviridae and derived vectors insert their genome into the host
      chromosome, the transgene delivered by these viruses are stably expressed in the
      infected cells. From a safety standpoint, the vectors are designed to eliminate
      any need to carry viral genes or associated toxicities into the host cell. This
      also substantially reduces their potential immunogenicity. Finally, the titers
      achieved with these vectors can be very high, yielding efficient infection in a
      broad range of cell types.

PMID- 14970607
TI  - Stable gene delivery to CNS cells using lentiviral vectors.
AB  - Recombinant viral vectors have been used to study a variety of fundamental issues
      in developmental neurobiology, as well as pathogenesis and treatments for various
      neurodegenerative diseases. Lentiviral vectors are valuable tools for
      neurobiology research owing to their ability to transduce nondividing cells, such
      as neurons, and to introduce therapeutic or reporter genes into central nervous
      system (CNS) cells in vivo and in vitro.

PMID- 14970608
TI  - Gene delivery to hematopoietic stem cells using lentiviral vectors.
AB  - Hematopoietic stem cells (HSCs) are clonogenic cells capable of both selfrenewal
      and multilineage differentiation. An efficient method for gene transfer into HSCs
      is required for exploring HSC biology as well as for gene therapy of
      hematopoietic disorders. Retroviral vectors have been the most widely used
      vectors for gene transfer to HSCs. However, retroviral vectors require cell
      division for integration, limiting their use for gene transfer into HSCs that are
      exclusively quiescent. Although prestimulation of HSCs with cytokines can enhance
      gene-transfer efficiency, exposure to cytokines also stimulates HSCs to
      differentiate, resulting in the reduction of long-term repopulating capacity (8
      15). In contrast, lentiviral vectors based on the human immunodeficiency virus
      type 1 (HIV-1) can efficiently transduce human CD34+ cells without cytokine
      prestimulation and long-term multilineage expression of the transgene is detected
      in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice after
      transplantation (16-22). Murine HSCs can also be easily transduced with
      lentiviral vectors without cytokine prestimulation (23-26). In this chapter, the
      protocols for transduction of human CD34+ cells that contain HSCs are described.
      The procedures include the isolation of human CD34+ cells, preparation of
      lentiviral vectors, transduction of human CD34+ cells, and in vivo analysis of
      transduced HSCs using NOD/SCID mice.

PMID- 14970609
TI  - Delivery of genes to the eye using lentiviral vectors.
AB  - The primary aim of gene transfer into the retinal cells has been to investigate
      the developmental mechanisms of the retinal cells or to reverse retinal diseases.
      Retroviruses have been used to investigate the differentiation of retinal cells,
      to study the embryonic retina in vivo or explant organ culture, and to trace the
      fate of the cells that were dividing at the time of gene transfer. Using
      adenovirus, Bennett et al. showed the possibility of using gene therapy to
      correct degenerative diseases of the central nervous system (CNS) (6). However,
      owing to the short duration of the gene expression, adenovirus is not suitable
      for correcting chronic diseases. Currently, lentivirus (7-9) and adenoassociated
      virus vectors (10-14) are being used for studying and correcting gene therapy of
      retinal degenerative diseases. Using an HIV vector carrying the green fluorescent
      protein (GFP) gene expressed from the cytomegalovirus (CMV) promoter, we showed
      that efficient and long-lasting gene expression could be obtained in the retina
      (7,8). Moreover, gene expression was restricted to the photoreceptor cells and
      was more efficient with the rhodopsin promoter. Similar results were reported
      using adeno-associated virus (AAV) vector. Using a lentivirus vector carrying the
      phosphodiesterase beta subunit (PDEbeta) gene, the mutation of which causes
      retinal degeneration called retinitis pigmentosa in rd mice, photoreceptor cells
      were rescued from degeneration in rd mice for at least 6 mo by PDEbeta
      transduction using HIV-based lentivirus vector (9).

PMID- 14970610
TI  - Lentiviral transduction of human dendritic cells.
AB  - Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that play a
      pivotal role in stimulating antigen-specific T cells in vivo. The cardinal
      properties of DCs are: the ability to take up, process, and present antigens; (2)
      the ability to migrate through different tissues into lymphoid organs; and (3)
      the ability to interact with and stimulate T cells (3). Because of their unique
      capability of generating primary CD4+ and CD8+ T-cell responses, DCs are of
      particular interest for immunotherapeutic approaches to infectious disease and
      cancer. There are many ways to load DCs with antigen and to subsequently induce
      specific immune responses in vivo and in vitro. One strategy relies on
      genetically modified peripheral blood mononuclear cell (PBMC)-derived DCs to
      establish expression of a gene that encodes a specific antigen. In contrast to
      pulsing DCs with antigenic peptides or proteins, genetic engineering of DCs has
      the advantages of providing multiple epitopes for major histocompatibility class
      (MHC) class I-and MHC class II-restricted immune responses as well as a
      continuous supply of antigen for presentation alone or together with
      immunomodulatory proteins (cytokines, for example).

PMID- 14970611
TI  - Gene transfer by retroviral vectors: an overview.
AB  - Viruses have evolved to deliver their genetic cargo to cells and, due to the
      pathogenicity of some viruses, this process has been the subject of a great deal
      of study. In this respect, retroviruses came to the fore in the early 1900s with
      the demonstration by Ellermann and Bang and by Rous that chicken leukosis was
      caused by a virus, now referred to as avian sarcoma/leukosis virus (ASLV). This
      began a body of work that led to the identification of virus-induced tumors in
      mammalian species and retroviruses (as they are now called) were identified as
      the causative agents for a number of pathologies from tumors to acquired
      immunodefiencey syndrome (AIDS). Retroviruses were characterized as RNA viruses
      that replicate through a DNA intermediate. The study of retroviruses contributed
      and led to the elucidation of a number of diverse biological phenomena as the
      oncogenes carried by these viruses began to be identified as receptors, kinases,
      and transcription factors (3). The idea that these viruses could be used to ferry
      a gene of choice, rather than the viral genome, springs from the study of Rous
      sarcoma virus (RSV).

PMID- 14970612
TI  - Gene delivery to cells in culture using retroviruses.
AB  - Moloney leukemia virus-based vectors can be generated in cells that express the
      products of three retroviral genes, gag, pol, and env. There are a number of cell
      lines such as PG13 and FLYA13 (2), known as packaging cells, that have been
      established that stably express these genes. When these cells are transfected
      with vector DNA, they will generate retroviral transducing particles in the
      supernatant of the cells. The transducing particles can be produced by transient
      transfection of the packaging cells or from cells that have stably integrated the
      vector DNA into the packaging cell line. This is particularly useful if the
      vector will be required in large amounts for an extended period of time. The
      titer that can be achieved from transient transfection of DNA will be
      proportional to the transfection efficiency. In this respect, cells derived from
      the human embryonic kidney cell line 293 (3) are particularly useful because they
      can be transfected very efficiently (typically 90-99%) (4-7). Here I outline a
      method to generate vector transiently. Methods to generate stable packaging cell
      lines can be found elsewhere (8).

PMID- 14970613
TI  - Retrovirus-mediated gene transfer to tumors: utilizing the replicative power of
      viruses to achieve highly efficient tumor transduction in vivo.
AB  - Vectors derived from retroviruses have been widely studied as tools for gene
      transfer into mammalian tissue in vivo. One application for which retroviral
      vectors have received particular attention is gene transfer into tumor cells for
      treatment of cancer. Simple retroviruses, such as murine leukemia virus (MLV),
      and the vectors derived from them, require cell division for infection and thus
      possess a degree of inherent specificity for the rapidly dividing cells of
      neoplastic tissue. This unique property and the ease with which retroviral
      vectors are manipulated and produced have provided much of the impetus for their
      use in experimental and clinical cancer gene-therapy studies.

PMID- 14970614
TI  - Delivery of genes to hematopoietic stem cells.
AB  - Bone marrow hematopoiesis is maintained by hematopoietic stem cells (HSC).
      Because of their unique features to self-renew and differentiate along all
      lineages of hematopoietic cells, even a single HSC can completely reconstitute
      bone marrow hematopoiesis of irradiated recipients (2). Therefore, HSCs are
      considered to be the ideal target cell population in gene-therapy fields for
      genetic disorders that are susceptible to bone marrow transplantation (3).
      However, because most HSCs are quiescent, it is difficult to transduce them using
      retroviral vectors (4). Furthermore, retroviral vectors, especially Moloney
      murine leukemia virus (MMLV)-based retroviral vectors that have been commonly
      used in gene-therapy clinical trials, are very susceptible to de novo methylation
      in immature cells such as embryonic stem (ES) cells, embryonal carcinoma cells
      (EC), and HSCs, resulting in shut off/silencing of the transgene expression in
      vivo (5). This is another obstacle for successful gene delivery into HSCs.

PMID- 14970615
TI  - Delivery and expression of heterologous genes in mammalian cells using self
      replicating alphavirus vectors.
AB  - The RNA genomes of alphaviruses have been exploited to create highly efficient
      vectors for transient expression of foreign genes in mammalian cells and for use
      as vehicles for genetic vaccines. For Semliki Forest virus (SFV), a
      representative alphavirus, three strategies for in vitro and in vivo gene
      delivery have been developed. One method relies on the packaging of recombinant
      vectors into suicidal viral particles and infection of target cells, whereas the
      other two methods are based on direct transfection of target cells, either by
      using naked DNA encoding the SFV replicon placed downstream of an RNA polymerase
      II dependent promoter, or by using in vitro transcribed RNA encoding the SFV
      replicon. All three approaches result in the delivery of a selfreplicating SFV
      vector into target cells, with expression of foreign genes being driven from a
      highly efficient viral subgenomic promoter.

PMID- 14970616
TI  - Chiral separation principles: an introduction.

PMID- 14970617
TI  - Separation of enantiomers by thin-layer chromatography: an overview.

PMID- 14970618
TI  - Cyclodextrin-based chiral stationary phases for liquid chromatography: a twenty
      year overview.

PMID- 14970619
TI  - Enantiomeric separations by HPLC using macrocyclic glycopeptide-based chiral
      stationary phases: an overview.

PMID- 14970620
TI  - Chiral separation by HPLC using polysaccharide-based chiral stationary phases.

PMID- 14970621
TI  - Applications of polysaccharide-based chiral stationary phases for resolution of
      different compound classes.

PMID- 14970622
TI  - Chiral separation by HPLC with pirkle-type chiral stationary phases.

PMID- 14970623
TI  - Chiral separation by HPLC using the ligand-exchange principle.

PMID- 14970624
TI  - Chiral separations by HPLC using molecularly imprinted polymers.

PMID- 14970625
TI  - Indirect enantioseparation by HPLC using chiral benzofurazan-bearing reagents.

PMID- 14970626
TI  - Separation of racemic trans-stilbene oxide by sub-/supercritical fluid
      chromatography.

PMID- 14970627
TI  - Chiral separations using the macrocyclic antibiotics in capillary
      electrophoresis.

PMID- 14970628
TI  - Enantioresolutions by capillary electrophoresis using glycopeptide antibiotics.

PMID- 14970629
TI  - Separation of enantiomers by capillary electrophoresis using cyclodextrins.

PMID- 14970630
TI  - Chiral separations by capillary electrophoresis using proteins as chiral
      selectors.

PMID- 14970631
TI  - Cellulases as chiral selectors in capillary electrophoresis.

PMID- 14970632
TI  - Use of chiral crown ethers in capillary electrophoresis.

PMID- 14970633
TI  - Chiral separations by capillary electrophoresis using cinchona alkaloid
      derivatives as chiral counter-ions.

PMID- 14970634
TI  - Chiral separation by capillary electrophoresis using polysaccharides.

PMID- 14970635
TI  - Chiral micellar electrokinetic chromatography.

PMID- 14970636
TI  - Chiral separation by capillary electrophoresis in nonaqueous medium.

PMID- 14970637
TI  - Chiral ligand-exchange capillary electrophoresis and capillary
      electrochromatography.

PMID- 14970638
TI  - Enantioseparation in capillary chromatography and capillary electrochromatography
      using polysaccharide-type chiral stationary phases.

PMID- 14970639
TI  - Chiral separation by capillary electrochromatography using cyclodextrin phases.

PMID- 14970640
TI  - Chiral separations by capillary electrochromatography using molecularly imprinted
      polymers.

PMID- 14970641
TI  - Methods to induce cell cycle checkpoints.

PMID- 14970642
TI  - Methods for synchronizing mammalian cells.

PMID- 14970643
TI  - Enrichment of cells in different phases of the cell cycle by centrifugal
      elutriation.

PMID- 14970644
TI  - Analysis of the mammalian cell cycle by flow cytometry.

PMID- 14970645
TI  - Methods for detecting cells in S phase.

PMID- 14970646
TI  - Yeast cell synchronization.

PMID- 14970647
TI  - Analysis of the budding yeast Saccharomyces cerevisiae cell cycle by
      morphological criteria and flow cytometry.

PMID- 14970648
TI  - Analysis of the fission yeast Schizosaccharomyces pombe cell cycle.

PMID- 14970649
TI  - Strategies to isolate evolutionarily conserved cell cycle regulatory genes.

PMID- 14970650
TI  - Microarray approaches for analysis of cell cycle regulatory genes.

PMID- 14970651
TI  - Using the yeast genome-wide gene-deletion collection for systematic genetic
      screens.

PMID- 14970652
TI  - Gene targeting in cultured human cells.

PMID- 14970653
TI  - Use of in vivo gap repair for isolation of mutant alleles of a checkpoint gene.

PMID- 14970654
TI  - In vitro mutagenesis to define functional domains.

PMID- 14970655
TI  - Use of gene overexpression to assess function in cell cycle control.

PMID- 14970656
TI  - Histone acetylation/deacetylation as a regulator of cell cycle gene expression.

PMID- 14970657
TI  - Cataloging proteins in cell cycle control.

PMID- 14970658
TI  - Multidimensional proteomic analysis of proteolytic pathways involved in cell
      cycle control.

PMID- 14970659
TI  - Purification and identification of protein complexes that control the cell cycle.

PMID- 14970660
TI  - Xenopus cell-free extracts to study DNA damage checkpoints.

PMID- 14970661
TI  - Protein-protein interactions.

PMID- 14970662
TI  - Detection of kinase and phosphatase activities.

PMID- 14970663
TI  - Monitoring changes in the subcellular location of proteins in S. cerevisiae.

PMID- 14970664
TI  - Chromosomal changes and cell cycle checkpoints in Mammalian cells.

PMID- 14970665
TI  - Detecting the influence of cell cycle regulatory proteins on human telomeres.

PMID- 14970666
TI  - Monitoring spindle assembly and disassembly in yeast by indirect
      immunofluorescence.

PMID- 14970668
TI  - Indices of oxidative stress in eutopic and ectopic endometria of women with
      endometriosis.
AB  - This study was designed to determine the activities of superoxide dismutase and
      glutathione peroxidase and some of the lipid peroxidation indices
      (malondialdehyde and total sulfhydryl groups) in eutopic and ectopic endometria
      of patients with endometriosis. Ectopic endometrial tissues (ovarian cysts; n =
      22) were obtained laparoscopically during the preovulatory period. Statistical
      analyses were made using the Wilcoxon signed-rank test. The levels of
      malondialdehyde and total sulfhydryl groups were similar in the eutopic and
      ectopic endometria, whereas the superoxide dismutase activity was found to be
      significantly higher in the latter (1,893 +/- 780 vs. 3,512 +/- 1,502 U/g
      protein; p = 0.002). Although the glutathione peroxidase activity was slightly
      lower in the ectopic than in the eutopic tissues, the difference was not found to
      be statistically significant. The malondialdehyde levels were positively
      correlated with the plasma 17beta-estradiol concentrations in the ectopic
      endometria (r = 0.683, p = 0.001). No such correlation was seen in the eutopic
      tissue. It is suggested that various factors, such as cytokines released by
      activated macrophages in the peritoneal fluid and 17beta-estradiol itself
      synthesized by the ovaries, may locally affect the oxidant status of ectopic
      endometria.

PMID- 14970669
TI  - Resveratrol, a red wine constituent polyphenol, protects from ischemia
      reperfusion damage of the ovaries.
AB  - OBJECTIVE: The aim of this study is to investigate the effects of resveratrol on
      histopathological changes, antioxidant status and lipid peroxidation, in torsion
      detorsion injury in rat ovaries. METHOD: To determine whether ischemia followed
      by reperfusion can induce ovarian oxidative damage, we created a model of adnexal
      ischemia-reperfusion by using rats. Ischemia was induced by unilateral occlusion
      of the tubo-ovarian vessels for 3 h. Reperfusion was achieved by releasing the
      occlusion and restoring the circulation for 3 h. Thirty-two adult female albino
      rats were divided equally into 4 groups: sham operation, torsion,
      saline/detorsion and resveratrol/detorsion. Rats in the torsion group were killed
      after 360 degrees clockwise adnexal torsion for 3 h. Resveratrol was injected
      intraperitoneally 30 min before detorsion in the resveratrol/detorsion group, and
      saline was administered in the saline/detorsion group. After 3 h of adnexal
      detorsion in both of these groups, the rats were killed and adnexa were removed.
      The tissue levels of malondialdehyde, reduced glutathione and xanthine oxidase
      activity were measured. RESULTS: Malondialdehyde and xanthine oxidase levels in
      the saline/detorsion group were increased significantly when compared to the
      torsion and sham operation groups (p < 0.001). Malondialdehyde levels in the
      resveratrol group were lower than in the saline/detorsion group, and differences
      between the two groups were statistically significant (p < 0.001). Xanthine
      oxidase levels in the resveratrol group were lower than in the saline/detorsion
      and torsion groups, and differences between these groups were statistically
      significant (p < 0.001). Reduced glutathione levels in the saline/detorsion group
      were decreased significantly when compared to the torsion and sham operation
      groups. Reduced glutathione levels in the resveratrol group were significantly
      higher than in the saline/detorsion group (p < 0.006). Histological examination
      showed a significant improvement in ovarian morphology in the resveratrol-treated
      rats compared with the ischemia and ischemia-reperfusion groups. CONCLUSION: Our
      results demonstrated that intraperitoneal resveratrol administration reduced the
      lipid peroxidation products of ischemic rats and ovarian damage was reduced as
      indicated by histological examination.

PMID- 14970670
TI  - Gram-negative bacterial endotoxin- induced infertility: a birds eye view.
AB  - Alleviation of infertility on the one hand and development of improved methods of
      contraception on the other are global concerns to woman's health. The molecular
      signals that regulate implantation are of clinical relevance since understanding
      the nature of these signals may lead to strategies to correct implantation
      failure and to develop novel contraceptive approaches. The other pressing concern
      is the poor pregnancy rate resulting from in vitro fertilization (IVF). The
      pregnancy rate in IVF programs remains about 20-30% in spite of the high rate of
      successful fertilization. This has led to the proposition that additional uterine
      factors, critical for the implantation process, must be limiting. Identification
      of such parameters could help in determining the appropriate physiological state
      of the uterus for embryo transfer. Several factors are known to have a direct or
      indirect impact on the ability of the uterus to develop to a functionally
      receptive state. This would disrupt the normal coordination between embryonic and
      uterine development even though all molecular players may seem otherwise normal.

PMID- 14970671
TI  - From biochemical genetics to DNA sequencing and beyond: the changing face of
      animal genomics.

PMID- 14970672
TI  - The future of cattle genome research: the beef is here.

PMID- 14970673
TI  - Mapping of 195 genes in cattle and updated comparative map with man, mouse, rat
      and pig.
AB  - Our on-going goal is to improve and update the comparative genome organization
      between cattle and man but also among the most detailed mammalian species genomes
      i.e. cattle, mouse, rat and pig. In this work, we localized 195 genes in cattle
      and checked all human/bovine non-concordant localizations found in the
      literature. Next, we compiled all the genes mapped in cattle, goat, sheep and pig
      (2,166) for which the human ortholog with its chromosomal position is known,
      added corresponding data in mouse and rat, and ordered the genes relatively to
      the human genome sequence. We estimate that our compilation provides bovine
      mapping information for about 89% of the human autosomes. Thus, a near complete,
      overall and detailed picture of the number, distribution and extent of bovine
      conserved syntenies (regardless of gene order) on human R-banded autosomes is
      proposed as well as a comparison with mouse, rat and pig genomes.

PMID- 14970674
TI  - Development of a comprehensive comparative radiation hybrid map of bovine
      chromosome 7 (BTA7) versus human chromosomes 1 (HSA1), 5 (HSA5) and 19 (HSA19).
AB  - In this study, we present a comprehensive 3,000-rad radiation hybrid (RH) map of
      bovine chromosome 7 (BTA7) with 108 markers including 54 genes or ESTs. For 52 of
      them, a human ortholog sequence was found either on HSA1 (one gene), HSA5 (31
      genes) or HSA19 (19 genes and one non-annotated sequence) confirming previously
      described syntenies. Moreover, in order to refine boundaries of blocks of
      conserved synteny, nine new genes were mapped to the bovine genome on the basis
      of their localization on the human genome: six on BTA7 and originating from HSA1
      (TRIM17), HSA5 (MAN2A1, LMNB1, SIAT8D and FLJ1159) and HSA19 (VAV1), and the
      three others (AP3B1, APC and CCNG1) on BTA10. The available draft of the human
      genome sequence allowed us to present a detailed picture of the distribution of
      conserved synteny segments between man and cattle. Finally, the INRA bovine BAC
      library was screened for most of the BTA7 markers considered in this study to
      provide anchors for the bovine physical map.

PMID- 14970675
TI  - A comparative map of bovine chromosome 19 based on a combination of mapping on a
      bacterial artificial chromosome scaffold map, a whole genome radiation hybrid
      panel and the human draft sequence.
AB  - We have constructed a medium density physical map of bovine chromosome 19 using a
      combination of mapping loci on both a bovine bacterial artificial chromosome
      (BAC) scaffold map and a whole genome radiation hybrid (WGRH) panel. The
      resulting map contains 70 loci spanning the length of bovine chromosome 19. Three
      contiguous groups of BACs were identified on the basis of multiple loci mapping
      to individual BAC clones. Bovine chromosome 19 was found in this study to be
      comprised almost entirely from regions of human chromosome 17, with a small
      region putatively assigned to human chromosome 10. Fourteen breakpoints between
      the bovine and human chromosomes were detected, with a possibility of five more
      based on ordering of the WGRH map.

PMID- 14970676
TI  - Comparative FISH-mapping of the survival of motor neuron gene (SMN) in domestic
      bovids.
AB  - A comparative fluorescence in situ mapping of the SMN gene was performed on R
      banded chromosome preparations of cattle (Bos taurus, BTA, 2n = 60), river
      buffalo (Bubalus bubalis, BBU, 2n = 50), sheep (Ovis aries, OAR, 2n = 54) and
      goat (Capra hircus, CHI, 2n = 60), as well as on those of a calf from Piedmont
      breed affected by arthrogryposis. SMN was located on BTA20q13.1, OAR16q13.1,
      CHI20q13.1 and BBU19q13. These chromosomes and chromosome bands are believed to
      be homeologous, confirming the high degree of chromosome homeologies among
      bovids. The position of SMN was refined in cattle, compared to the two previous
      localizations, while it is a new gene assignment in the other three bovids. A
      comparative fiber-FISH performed on extended chromatin of both normal cattle and
      calf affected by arthrogryposis revealed more extended FITC signals in the calf,
      compared to the normal cattle (control), suggesting a possible duplication of the
      SMN gene in the calf affected by arthrogryposis. .

PMID- 14970677
TI  - Genomic organization of the DGAT2/MOGAT gene family in cattle (Bos taurus) and
      other mammals.
AB  - We report the cloning and initial characterization of the genes encoding DGAT2
      (diacylglycerol transferase 2), MOGAT1 and MOGAT2 (monoacylglycerol transferases
      1 and 2) in domestic cattle (Bos taurus). The three closely related genes belong
      to a gene family with at least eight members in mammals and are candidate genes
      for quantitative traits related to dietary fat uptake, lipid synthesis and
      storage. MOGAT2 and DGAT2 form a tandem and were mapped to bovine chromosome
      (BTA) 15q25-->q26 by fluorescence in situ hybridization. MOGAT1 was localized to
      BTA 2q43-->q44. The three genes were investigated for polymorphisms that might be
      associated with breeding values for milk fat percentage in the dairy breeds
      German Holstein, German Simmental and German Brown. All the detected
      polymorphisms were located outside exons or, with one exception, were silent. In
      MOGAT1, a missense mutation in exon 4 was found that causes a non-conservative
      substitution of cysteine170 (uncharged, hydrophobic) by lysine (positively
      charged, hydrophilic). However, allele frequency estimates from pooled DNA
      samples revealed no significant association of the observed polymorphisms with
      breeding values for milk fat percentage. A comparative analysis of chromosomal
      locations and exon-intron structure of the known members of the DGAT2/MOGAT gene
      family in humans, rodents and cattle indicates an ancient tandem duplication of
      the ancestor gene combined with an intron gain (or loss) in one copy. Further
      members of the family may have arisen by duplications of this gene tandem via two
      rounds of interchromosomal or genome duplications as well as further local
      (single) gene duplication and loss events.

PMID- 14970678
TI  - Sequence analysis of myostatin promoter in cattle.
AB  - Myostatin (GDF8) acts as a negative regulator of muscle growth. Mutations in the
      gene are responsible for the double muscling phenotype in several European cattle
      breeds. Here we describe the sequence of the upstream 5' region of the myostatin
      gene. The sequence analysis was carried out on three animals of nine European
      cattle breeds, with the aim to search for polymorphisms. A T/A polymorphism at 
      371 and a G/C polymorphism at -805 (relative to ATG) were found. PCR- RFLP was
      used to further screen 353 animals of the nine breeds studied and to assess the
      frequencies of the SNPs. The promoter region of the gene contains several binding
      sites for transcription factors found also in other myogenic genes. This may play
      an important role in the regulation of the protein and consequently on muscular
      development.

PMID- 14970679
TI  - Bovine Y chromosome microsatellite polymorphisms.
AB  - Thirty-eight bovine Y chromosome (BTAY) microsatellites (MS) were assessed for
      polymorphisms in DNA samples obtained from 17 unrelated bulls. Thirty-three of
      these microsatellites are new and were used for the construction of a first
      generation radiation hybrid map for BTAY (Liu et al., 2002). Five MS had been
      previously reported and were used as positive controls. Fourteen out of 38 MS
      were found to be polymorphic; the remaining 24 were uninformative among the
      animals tested. The number of hemizygous loci per MS within individual ranged
      from two to over 20. Seven MS presented smear- or ladder-like bands, a unique
      feature for Y chromosome multi-copy hemizygous MS loci. The locus length
      variance, within individual, ranged from 2 to 42 bp corresponding to the MS with
      the minimum and maximum number of loci observed, respectively. Within the 14
      polymorphic MS, the five pseudoautosomal MS, on average, were more polymorphic
      (35.3%) than the nine Y-specific MS (19.6%). Haplotypes resulting from
      combinations of these polymorphic loci will provide a powerful tool for future
      studies on the origin of domestic cattle and the evolution of bovid species.

PMID- 14970680
TI  - Development of a linkage map and QTL scan for growth traits in North American
      bison.
AB  - PCR protocols incorporating fluorescently labeled multiplexed primer combinations
      were developed to produce a linkage map for bison. Three hundred fifty eight
      microsatellite loci spanning all 29 autosomes were genotyped via 83 PCR
      multiplexes and nine individual amplifications. A total of 292 markers were
      integrated into an autosomal linkage map for bison. The sex averaged bison map
      (2,647 cM) was approximately 9% longer than the corresponding USDA MARC map,
      which covered 2,415 cM. Utilizing weaning, yearling and 17-month weights from two
      private bison herds, a QTL scan was conducted using the developed linkage map.
      LOD peaks suggestive of QTL were identified on chromosomes 2, 7, 15, and 24 for
      weaning weight, chromosomes 4, 14, and 15 for yearling weight and chromosomes 8,
      14, and 25 for 17-month weight. Four of the identified chromosomes have conserved
      synteny with regions harboring growth QTL in cattle.

PMID- 14970681
TI  - The river buffalo (Bubalus bubalis, 2n = 50) cytogenetic map: assignment of 64
      loci by fluorescence in situ hybridization and R-banding.
AB  - Sixty-four genomic BAC-clones mapping five type I (ADCYAP1, HRH1, IL3, RBP3B and
      SRY) and 59 type II loci, previously FISH-mapped to goat (63 loci) and cattle
      (SRY) chromosomes, were fluorescence in situ mapped to river buffalo R-banded
      chromosomes, noticeably extending the physical map of this species. All mapped
      loci from 26 bovine syntenic groups were located on homeologous chromosomes and
      chromosome regions of river buffalo and goat (cattle) chromosomes, confirming the
      high degree of chromosome homeologies among bovids. Furthermore, an improved
      cytogenetic map of the river buffalo with 293 loci from all 31 bovine syntenic
      groups is reported.

PMID- 14970682
TI  - Current status of the ovine genome map.
AB  - Genome maps in livestock species have been under development for the last decade.
      While the sheep map is one of the least advanced for livestock, the amount of
      available information is noteworthy, in light of the paucity of funding and
      personnel devoted to this project. These limited resources have been
      strategically aligned to take advantage of information from the human, mouse and
      bovine mapping and sequencing efforts. The resulting ovine linkage and physical
      maps have greatly enhanced the search for genes controlling important traits in
      sheep. In order to improve the efficiency of these investigations, it is
      imperative that efforts on the sheep comparative map be continued.

PMID- 14970683
TI  - Systematic screening of sheep skin cDNA libraries for microsatellite sequences.
AB  - 65,000 sheep skin cDNA clones were gridded in high density on to nylon membranes
      and screened for (CA)n and (GA)n repeat containing clones. 296 dinucleotide
      repeat-containing clones were identified with approximately 85% non-redundancy.
      Clones were single-pass 5' sequenced and we compared the Expressed Sequence Tag
      (EST) sequences to the Swiss-Prot database to ascertain their identity and/or
      putative function. We then aligned the ESTs against the human genomic sequence to
      determine the locations of human orthologous sequences. Finally, we developed a
      subset of polymorphic microsatellite markers and positioned them on the ovine
      linkage map.

PMID- 14970684
TI  - Identification of a novel ovine PrP polymorphism and scrapie-resistant genotypes
      for St. Croix White and a related composite breed.
AB  - Susceptibility to scrapie is primarily controlled by polymorphisms in the ovine
      prion protein gene (PRNP). Here, we report a novel ovine exon three PRNP
      polymorphism (SNP G346C; P116), its association with the ovine ARQ allele
      (P116A136R154Q171), and two new genotypes (PARQ/ARR; PARQ/ARQ) for the St. Croix
      White (SCW) breed and a related composite (CMP) breed developed for meat
      production. The (P116) polymorphism occurs between the N-terminal cleavage site
      and the hydrophobic region of the ovine prion protein, a region which exhibits
      extreme conservation across mammalian taxa. The relatively high frequency (0.75)
      of resistant ARR alleles and the absence of ARQ alleles for the SCW ewes used as
      breeding stock for CMP resulted in significant genic differentiation (P = 0.0123;
      S.E. = 0.00113). Additionally, the majority of the SCW (66.7%) and CMP (65.4%)
      sampled possessed genotypes considered resistant or nearly resistant to scrapie
      and experimental BSE (bovine spongiform encephalopathy.

PMID- 14970685
TI  - Allelic variants of ovine prion protein gene (PRNP) in Oklahoma sheep.
AB  - 1,144 sheep belonging to 21 breeds and known crosses were sequence analyzed for
      polymorphisms in the ovine PRNP gene. Genotype and allele frequencies of
      polymorphisms in PRNP known to confer resistance to scrapie, a fatal
      neurodegenerative disease of sheep, are reported. Known polymorphisms at codons
      136 (A/V), 154 (H/R) and 171 (Q/R/H/K) were identified. The frequency of the 171R
      allele known to confer resistance to type C scrapie was 53.8% and the frequency
      of the 136A allele known to influence the resistance to type A scrapie was
      96.01%. In addition, we report the identification of five new polymorphisms at
      codons 143 (H/R), 167 (R/S), 180 (H/Y), 195 (T/S) and 196 (T/S). We also report
      the identification of a novel allele (S/R) at codon 138.

PMID- 14970686
TI  - From a sow's ear to a silk purse: real progress in porcine genomics.
AB  - An incredible amount of progress has occurred in the past decade since the pig
      genome map began to develop. The porcine genetic linkage map now has nearly 5,000
      loci including several hundred genes, microsatellites and amplified fragment
      length polymorphism (AFLP) markers being added to the map. Thanks to somatic cell
      hybrid panels and then radiation hybrid panels the physical genetic map is also
      growing rapidly and now has over 4,000 genes and markers. Many quantitative trait
      loci (QTL) scans have been completed and together with candidate gene analyses
      have identified important chromosomal regions and individual genes associated
      with traits of economic interests. Using marker assisted selection (MAS) the
      commercial pig industry is actively using this information and traditional
      performance information to improve pig production. Large scale pig arrays are
      just now beginning to be used and co-expression of thousands of genes is now
      advancing our understanding of gene function. The pig's role in
      xenotransplantation and biomedical research makes the study of its genome
      important for the study of human disease. Sequencing of the pig genome appears on
      the near horizon. This commentary will discuss recent advances in pig genomics,
      directions for future research and the implications to both the pig industry and
      human health.

PMID- 14970687
TI  - A new contribution to the integration of human and porcine genome maps: 623 new
      points of homology.
AB  - In this study we examined homologies between 1,735 porcine microsatellites and
      human sequence. For 1,710 microsatellites we directly used the sequence flanking
      the repeat available in GenBank. For a set of 305 microsatellites, a BAC library
      was screened and end-sequencing provided 461 additional sequences. Altogether
      2,171 porcine sequences were tentatively aligned with the sequence of the human
      genome using the fasta program. Human homologies were observed for 652
      microsatellite loci and porcine chromosome assignments available for 623
      microsatellites provide useful links in the human and pig comparative map.
      Moreover for 92 STS, a significant sequence similarity was detected using at
      least two sequences and in all cases corresponding human locations were
      consistent. The present study allowed the integration of anonymous markers and
      the porcine linkage map into the framework of the comparative data between human
      and porcine genomes (http://w3.toulouse.inra.fr/lgc/pig/msat/). Moreover all
      conserved syntenic segments were defined on human chromosomes.

PMID- 14970688
TI  - Construction of a high-resolution comparative gene map between swine chromosome
      region 6q11-->q21 and human chromosome 19 q-arm by RH mapping of 51 genes.
AB  - A comprehensive and comparative map was constructed for the porcine chromosome
      (SSC) 6q11-->q21 region, where the gene(s) responsible for the maldevelopment of
      embryos are localized using swine populations of the National Institute of Animal
      Industry, Japan (NIAI). Since the chromosomal region corresponds to a region of
      human chromosome (HSA) 19q13.1-->q13.3 based on bi-directional chromosome
      painting, primer pairs were designed from porcine cDNA sequences identified, on a
      sequence comparison basis, as being transcripts from genes orthologous to those
      in the HSA region. Fifty-one genes were successfully assigned to a swine
      radiation hybrid (RH) map with LOD scores greater than 6. ERF and PSMD8 genes
      were assigned to SSC4 and SSC1, respectively. The remaining 49 genes were
      assigned to SSC6, demonstrating that the synteny between the SSC6 and HSA19
      chromosomal regions is essentially conserved, therefore confirming, the results
      of bi-directional chromosome painting. However, when examined precisely,
      rearrangements have apparently occurred within the region of conserved synteny.
      For the ERF and PSMD8 genes assigned to SSCs other than SSC6, additional mapping
      using somatic cell hybrid (SCH) panels was performed to confirm the results of RH
      mapping.

PMID- 14970689
TI  - Generation of a 5.5-Mb BAC/PAC contig of pig chromosome 6q1.2 and its integration
      with existing RH, genetic and comparative maps.
AB  - We generated a sequence-ready BAC/PAC contig spanning approximately 5.5 Mb on
      porcine chromosome 6q1.2, which represents a very gene-rich genome region. STS
      content mapping was used as the main strategy for the assembly of the contig and
      a total of 6 microsatellite markers, 53 gene-related STS and 116 STS
      corresponding to BAC and PAC end sequences were analyzed. The contig comprises
      316 BAC and PAC clones covering the region between the genes GPI and LIPE. The
      correct contig assembly was verified by RH-mapping of STS markers and comparative
      mapping of BAC/PAC end sequences using BLAST searches. The use of microsatellite
      primer pairs allowed the integration of the physical maps with the genetic map of
      this region. Comparative mapping of the porcine BAC/PAC contig with respect to
      the gene-rich region on the human chromosome 19q13.1 map revealed a completely
      conserved gene order of this segment, however, physical distances differ somewhat
      between HSA19q13.1 and SSC6q1.2. Three major differences in DNA content between
      human and pig are found in two large intergenic regions and in one region of a
      clustered gene family, respectively. While there is a complete conservation of
      gene order between pig and human, the comparative analysis with respect to the
      rodent species mouse and rat shows one breakpoint where a genome segment is
      inverted.

PMID- 14970690
TI  - Improving the comparative map of porcine chromosome 10 with respect to human
      chromosomes 1, 9 and 10.
AB  - ZOO-FISH mapping shows human chromosomes 1, 9 and 10 share regions of homology
      with pig chromosome 10 (SSC10). A more refined comparative map of SSC10 has been
      developed to help identify positional candidate genes for QTL on SSC10 from human
      genome sequence. Genes from relevant chromosomal regions of the public human
      genome sequence were used to BLAST porcine EST databases. Primers were designed
      from the matching porcine ESTs to assign them to porcine chromosomes using the
      INRA somatic cell hybrid panel (INRA-SCHP) and the INRA-University of Minnesota
      Radiation Hybrid Panel (IMpRH). Twenty-eight genes from HSA1, 9 and 10 were
      physically mapped: fifteen to SSC10 (ACO1, ATP5C1, BMI1, CYB5R1, DCTN3, DNAJA1,
      EPHX1, GALT, GDI2, HSPC177, OPRS1, NUDT2, PHYH, RGS2, VIM), eleven to SSC1 (ADFP,
      ALDHIB1, CLTA, CMG1, HARC, PLAA, STOML2, RRP40, TESK1, VCP and VLDLR) and two to
      SSC4 (ALDH9A1 and TNRC4). Two anonymous markers were also physically mapped to
      SSC10 (SWR1849 and S0070) to better connect the physical and linkage maps. These
      assignments have further refined the comparative map between SSC1, 4 and 10 and
      HSA1, 9 and 10.

PMID- 14970691
TI  - Improving the comparative map of porcine chromosome 9 with respect to human
      chromosomes 1, 7 and 11.
AB  - Conserved segments have been identified by ZOO-FISH between pig chromosome 9
      (SSC9) and human chromosomes 1, 7 and 11. To assist in the identification of
      positional candidate genes for QTL on SSC9, the comparative map was further
      developed. Primers were designed from porcine EST sequence homologous to genes in
      regions of human chromosomes 1, 7 and 11. Porcine ESTs were then physically
      assigned using the INRA somatic cell hybrid panel (INRASCHP) and the high
      resolution radiation hybrid panel (IMpRH). Seventeen genes (PEPP3, RAB7L1, FNBP2,
      MAPKAPK2, GNAI1, ABCB1, STEAP, AKAP9, CYP51A1, SGCE, ROBO4, SIAT4C, GLUL,
      CACNA1E, PTGS2, C1orf16 and ETS1) were mapped to SSC9, while GUSB, CPSF4 and THG
      1 were assigned to SSC3.

PMID- 14970692
TI  - A refined comparative map between porcine chromosome 13 and human chromosome 3.
AB  - We report here the localisation of BAIAP1 (13q24), HTR1F (13q45), PTPRG (13q23)
      and UBE1C (13q24) by fluorescence in situ hybridisation (FISH), and BAIAP1
      (Swr2114; 21 cR; LOD = 11.03), GATA2 (Sw2448; 37 cR; LOD = 8.26), IL5RA (Swr2114;
      64 cR; LOD = 3.85), LMCD1 (Sw2450; 61 cR; LOD = 4.73), MME (CP; 50 cR; LOD =
      7.75), RYK (Swc22; 12 cR; LOD = 18.62) and SGU003 (Sw1876; 6 cR; LOD = 16.99) by
      radiation hybrid (RH) mapping to porcine chromosome 13 (SSC13). The mapping of
      these 10 different loci (all mapped to human chromosome 3; HSA3) not only
      confirms the extended conservation of synteny between HSA3 and SSC13, but also
      defines more precisely the regions with conserved linkage. The syntenic region of
      the centromeric part of SSC13 was determined by isolating porcine bacterial
      artificial chromosome (BAC) clones (842D4 and 1031H1) using primers amplifying
      porcine microsatellite markers S0219 and S0076 (mapped to this region). Sequence
      comparison of the BAC end sequences with the human genome sequence showed that
      the centromeric part of SSC13 is homologous with HSA3p24.

PMID- 14970693
TI  - Comparative mapping of genes flanking the human chromosome 12 evolutionary
      breakpoint in the pig.
AB  - Genes located on human chromosome 12 (HSA12) are conserved on pig chromosomes 5
      and 14 (SSC5 and SSC14), with HSA12q23.3-->q24.11 harboring the evolutionary
      breakpoint between these chromosomes. For this study, pig sequence-tagged sites
      (STS) were developed for nine HSA12 genes flanking this breakpoint. Radiation
      hybrid (RH) mapping using the IMpRH panel revealed that COL2A1, DUSP6, KITLG, PAH
      and STAB2 map to SSC5, while PXN, PLA2G1B, SART3 and TCF1 map to SSC14.
      Polymorphisms identified in COL2A1, DUSP6, PAH, PLA2G1B and TCF1 were used for
      genetic linkage mapping and confirmed the map locations for these genes. Our
      results indicate that the HSA12 evolutionary breakpoint occurs between STAB2 and
      SART3 in a region spanning less than five million basepairs. These results refine
      the comparative map of the HSA12 evolutionary breakpoint region and help to
      further elucidate the extensive gene order rearrangements between HSA12 and SSC5
      and 14.

PMID- 14970694
TI  - Study of candidate genes for glycolytic potential of porcine skeletal muscle:
      identification and analysis of mutations, linkage and physical mapping and
      association with meat quality traits in pigs.
AB  - Several genes (PRKAA2, PRKAB1, PRKAB2, PRKAG3, GAA, GYS1, PYGM, ALDOA, GPI, LDHA,
      PGAM2 and PKM2), chosen according to their role in the regulation of the energy
      balance and in the glycogen metabolism and glycolysis of the skeletal muscle,
      were studied. Eleven single nucleotide polymorphisms (SNPs) were identified in
      six of these genes (PRKAB1, GAA, PYGM, LDHA, PGAM2 and PKM2). Allele frequencies
      were analyzed in seven different pig breeds for these loci and for a polymorphism
      already described for GPI and for three polymorphic sites already reported at the
      PRKAG3 locus (T30N, G52S and I199V). Linkage mapping assigned PYGM and LDHA to
      porcine chromosome (SSC) 2, PKM2 to SSC7, GAA to SSC12, PRKAB1 to SSC14 and PGAM2
      to SSC18. Physical mapping, obtained by somatic cell hybrid panel analysis,
      confirmed the linkage assignments of PRKAB1 and GAA and localized ALDOA, PRKAB2
      and GYS1 to SSC3, SSC4 and SSC6, respectively. Pigs selected for the association
      study, for which several meat quality traits were measured, were first genotyped
      at the PRKAG3 R200Q polymorphic site (RN locus), in order to exclude carriers of
      the 200Q allele, and then were genotyped for all the mutations considered in this
      work. Significant associations (P < or = 0.001) were observed for the PRKAG3 T30N
      and G52S polymorphic sites with meat colour (L* at 24 h post mortem). PGAM2 and
      PKM2 were significantly associated (P = 0.01) with drip loss percentage and
      glycogen content at one hour post mortem, respectively.

PMID- 14970695
TI  - Mapping, identification of polymorphisms and analysis of allele frequencies in
      the porcine skeletal muscle myopalladin and titin genes.
AB  - Genes coding for sarcomeric proteins may play a key role in muscle mass accretion
      and meat production. Screening a skeletal muscle cDNA library we isolated two
      partial sequences coding for the sarcomeric myopalladin and titin genes. In the
      present work we identified three SNPs in the 3' untranslated region, two at the
      myopalladin locus and one at the titin locus. Myopalladin was mapped on porcine
      chromosome (SSC) 14 using a somatic cell hybrid panel, a radiation hybrid panel
      and by linkage mapping. The linkage mapping of titin confirmed the position on
      SSC15. Then we analysed the allelic distribution of the alleles at both loci in
      six different porcine breeds. The analysis of the allele frequencies for these
      two loci in extremely divergent groups of pigs selected according to lean cuts
      (LC) and average daily gain (ADG) approached the significance level for
      myopalladin and LC trait. Further studies are needed to test the presence of a
      putative effect of myopalladin on lean meat content.

PMID- 14970696
TI  - Linkage and comparative mapping of the locus controlling susceptibility towards
      E. COLI F4ab/ac diarrhoea in pigs.
AB  - In 1995, Edfors-Lilja and coworkers mapped the locus for the E. COLI K88ab (F4ab)
      and K88ac (F4ac) intestinal receptor to pig chromosome 13 (SSC13). Using the same
      family material we have refined the map position to a region between the
      microsatellite markers Sw207 and Sw225. Primers from these markers were used to
      screen a pig BAC library and the positive clones were used for fluorescent in
      situ hybridization (FISH) analysis. The results of the FISH analysis helped to
      propose a candidate gene region in the SSC13q41-->q44 interval. Shotgun
      sequencing of the FISH-mapped BAC clones revealed that the candidate region
      contains an evolutionary breakpoint between human and pig. In order to further
      characterise the rearrangements between SSC13 and human chromosome 3 (HSA3),
      detailed gene mapping of SSC13 was carried out. Based on this mapping data we
      have constructed a detailed comparative map between SSC13 and HSA3. Two candidate
      regions on human chromosome 3 have been identified that are likely to harbour the
      human homologue of the gene responsible for susceptibility towards E. COLI
      F4ab/ac diarrhoea in pigs.

PMID- 14970697
TI  - Comparative sequence analysis of the PRKAG3 region between human and pig:
      evolution of repetitive sequences and potential new exons.
AB  - The PRKAG3 gene encodes the gamma3 chain of AMP-activated protein kinase (AMPK).
      A non-conservative missense mutation in the PRKAG3 gene causes a dominant
      phenotype involving abnormally high glycogen content in pig skeletal muscle. We
      have determined >126 kb (in 13 contigs) of porcine genomic sequence surrounding
      the PRKAG3 gene and the corresponding mouse region covering the gene. A
      comparison of these PRKAG3 sequences and the human sequence was conducted and
      used to predict evolutionarily conserved regions, including regulatory regions. A
      comparison of the human genomic sequence and a porcine BAC sequence containing
      the PRKAG3 gene, revealed a conserved organization and the presence of three
      additional genes, CYP27A1 (cytochrome P450, family 27, subfamily A, polypeptide
      1), STK36 (Serine Threonine Kinase 36), and the homolog of the unidentified human
      mRNA KIAA0173. Interspersed repetitive elements constituted 51.4 and 38.6% of
      this genomic region in human and pig, respectively. We were able to reliably
      align 12.6 kb of orthologous repeats shared between pig and human and these
      showed an average sequence identity of 72.4%. Our analysis revealed that the
      human KIAA0173 gene harbors alternative 5' untranslated exons originating from
      repetitive elements. This provides an obvious example how transposable elements
      may affect gene evolution.

PMID- 14970698
TI  - Chromosome location, genomic organization of the porcine COL10A1 gene and model
      structure of the NC1 domain.
AB  - The porcine COL10A1 gene, encoding the alpha1(X) chain of type X collagen, has
      been sequenced. The gene structure is evolutionarily conserved, consisting of
      three exons and two introns spanning 7100 bp. Linkage mapping localized the gene
      to chromosome 1, which is in agreement with human-pig homology maps. Furthermore,
      protein structure comparison of the functionally important carboxyl domain
      between species revealed that amino acid changes were few and mainly situated in
      loop regions.

PMID- 14970699
TI  - Aneuploidy detection in porcine embryos using fluorescence in situ hybridization.
AB  - In contrast to human embryos, there are very few studies published on the
      frequency of chromosomal aneuploidy in farm animals. The objectives of this study
      were to apply a three-color fluorescent in situ hybridization (FISH) method for
      evaluating aneuploidy in porcine embryos using chromosome-specific DNA probes,
      establish baseline frequencies of aneuploidy in embryos and compare the results
      with our previous findings of aneuploidy in spermatozoa and oocytes. The embryos
      were collected from superovulated gilts, which were slaughtered 48 h after
      insemination. FISH was performed using probes specific for the centromeric
      regions of porcine chromosomes 1, 10 and Y. Altogether 403 blastomeres from 114
      porcine embryos were successfully investigated. Diploidy was observed in 101
      (88.6%) embryos, triploidy in 2 (1.8%) embryos, mosaicism/mixoploidy in 9 (7.9%)
      embryos, and trisomy for chromosomes 1 or 10 in 2 (1.8%) embryos. No blastomere
      showed aneuploidy for chromosome Y. These findings correspond with the
      frequencies of aneuploidy we have found previously in porcine germ cells.

PMID- 14970700
TI  - Equine genomics: galloping to new frontiers.
AB  - Analysis of the horse genome is proceeding at a rapid pace. Within a short span
      of 6-7 years, approximately 1,500 markers have been mapped in horse, of which at
      least half are genes/ESTs. Health, performance and phenotypic characteristic are
      of major concern/interest to horse breeders and owners. Current efforts to
      analyze the equine genome are primarily aimed at developing critical resources
      (including an advanced gene map) that could readily be used in the near future to
      i) identify genes and mutations responsible for inherited equine
      diseases/disorders and to formulate approaches for accurate diagnostics,
      therapeutics and prevention, ii) discover genes associated with various other
      traits of significance, e.g. fertility, disease resistance, coat color and
      athletic performance etc., and iii) use functional genomic approaches to identify
      gene regulatory events involved in the manifestation of various diseases.

PMID- 14970701
TI  - An ordered BAC contig map of the equine major histocompatibility complex.
AB  - A physical map of ordered bacterial artificial chromosome (BAC) clones was
      constructed to determine the genetic organization of the horse major
      histocompatibility complex. Human, cattle, pig, mouse, and rat MHC gene sequences
      were compared to identify highly conserved regions which served as source
      templates for the design of overgo primers. Thirty-five overgo probes were
      designed from 24 genes and used for hybridization screening of the equine USDA
      CHORI 241 BAC library. Two hundred thirty-eight BAC clones were assembled into
      two contigs spanning the horse MHC region. The first contig contains the MHC
      class II region and was reduced to a minimum tiling path of nine BAC clones that
      span approximately 800 kb and contain at least 20 genes. A minimum tiling path of
      a second contig containing the class III/I region is comprised of 14 BAC clones
      that span approximately 1.6 Mb and contain at least 34 genes. Fluorescence in
      situ hybridization (FISH) using representative clones from each of the three
      regions of the MHC localized the contigs onto ECA20q21 and oriented the regions
      relative to one another and the centromere. Dual-colored FISH revealed that the
      class I region is proximal to the centromere, the class II region is distal, and
      the class III region is located between class I and II. These data indicate that
      the equine MHC is a single gene-dense region similar in structure and
      organization to the human MHC and is not disrupted as in ruminants and pigs.

PMID- 14970702
TI  - Comparative sequence analysis of equine and human MHC class II DQB genes.
AB  - The MHC class II DQB gene of horse was isolated and characterized. No obvious
      mutations causing frame shifts, or destruction of putative protein structure and
      splicing machinery were detected. Nucleotide sequence of exon 2 was consistent
      with an allelic sequence of the W23 haplotype. The cytoplasmic region of the
      equine DQB gene comprised two exons and an intron. A novel fragment of the gene
      was identified at the 3' intergenic region proximal to the ELA-DQB gene by
      sequence comparison between the human and horse DQB genes. This sequence showed
      the highest identity to exon 3 region of the DQB gene, however the 5' half of
      this exon was truncated as compared with the intact exon. This gene fragment was
      also identified in the same site of the HLA-DQB gene.

PMID- 14970703
TI  - Genetic mapping of GBE1 and its association with glycogen storage disease IV in
      American Quarter horses.
AB  - Comparative biochemical and histopathological data suggest that a deficiency in
      the glycogen branching enzyme (GBE) is responsible for a fatal neonatal disease
      in Quarter Horse foals that closely resembles human glycogen storage disease type
      IV (GSD IV). Identification of DNA markers closely linked to the equine GBE1 gene
      would assist us in determining whether a mutation in this gene leads to the GSD
      IV-like condition. FISH using BAC clones as probes assigned the equine GBE1 gene
      to a marker deficient region of ECA26q12-->q13. Four other genes, ROBO2, ROBO1,
      POU1F1, and HTR1F, that flank GBE1 within a 10-Mb segment of HSA3p12-->p11, were
      tightly linked to equine GBE1 when analyzed on the Texas A&M University 5000 rad
      equine radiation hybrid panel, while the GLB1, MITF, RYBP, and PROS1 genes that
      flank this 10-Mb interval were not linked with markers in the GBE1 group. A
      polymorphic microsatellite (GBEms1) in a GBE1 BAC clone was then identified and
      genetically mapped to ECA26 on the Animal Health Trust full-sibling equine
      reference family. All Quarter Horse foals affected with GSD IV were homozygous
      for an allele of GBEms1, as well as an allele of the most closely linked
      microsatellite marker, while a control horse population showed significant
      allelic variation with these markers. This data provides strong molecular genetic
      support for the candidacy of the GBE1 locus in equine GSD IV.

PMID- 14970704
TI  - The epitheliogenesis imperfecta locus maps to equine chromosome 8 in American
      Saddlebred horses.
AB  - Epitheliogenesis imperfecta (EI) is a hereditary junctional mechanobullous
      disease that occurs in newborn American Saddlebred foals. The pathological signs
      of epitheliogenesis imperfecta closely match a similar disease in humans known as
      Herlitz junctional epidermolysis bullosa, which is caused by a mutation in one of
      the genes (LAMA3, LAMB3 and LAMC2) coding for the subunits of the laminin 5
      protein (laminin alpha3, laminin beta3 and laminin gamma2). The LAMA3 gene has
      been assigned to equine chromosome 8 and LAMB3 and LAMC2 have been mapped to
      equine chromosome 5. Linkage disequilibrium between microsatellite markers that
      mapped to equine chromosome 5 and equine chromosome 8 and the EI disease locus
      was tested in American Saddlebred horses. The allele frequencies of
      microsatellite alleles at 11 loci were determined for both epitheliogenesis
      imperfecta affected and unaffected populations of American Saddlebred horses by
      genotyping and direct counting of alleles. These were used to determine fit to
      Hardy-Weinberg equilibrium for control and EI populations using Chi square
      analysis. Two microsatellite loci located on equine chromosome 8q, ASB14 and
      AHT3, were not in Hardy-Weinberg equilibrium in affected American Saddlebred
      horses. In comparison, all of the microsatellite markers located on equine
      chromosome 5 were in Hardy-Weinberg equilibrium in affected American Saddlebred
      horses. This suggested that the EI disease locus was located on equine chromosome
      8q, where LAMA3 is also located.

PMID- 14970705
TI  - Molecular characterization and mutational screening of the PRKAG3 gene in the
      horse.
AB  - The PRKAG3 gene encodes a muscle-specific isoform of the regulatory gamma subunit
      of AMP-activated protein kinase (AMPK). A major part of the coding PRKAG3
      sequence was isolated from horse muscle cDNA using reverse-transcriptase (RT)-PCR
      analysis. Horse-specific primers were used to amplify genomic fragments
      containing 12 exons. Comparative sequence analysis of horse, pig, mouse, human,
      Fugu, and zebrafish was performed to establish the exon/intron organization of
      horse PRKAG3 and to study the homology among different isoforms of AMPK gamma
      genes in vertebrates. The results showed conclusively that the three different
      isoforms (gamma1, gamma2, and gamma3) were established already in bony fishes.
      Seven single nucleotide polymorphisms (SNPs), five causing amino acid
      substitutions, were identified in a screening across horse breeds with widely
      different phenotypes as regards muscle development and intended performance. The
      screening of a major part of the PRKAG3 coding sequence in a small case/control
      material of horses affected with polysaccharide storage myopathy did not reveal
      any mutation that was exclusively associated with this muscle storage disease.
      The breed comparison revealed several potentially interesting SNPs. One of these
      (Pro258Leu) occurs at a residue that is highly conserved among AMPK gamma genes.
      In an SNP screening, the variant allele was only found in horse breeds that can
      be classified as heavy (Belgian) or moderately heavy (North Swedish Trotter,
      Fjord, and Swedish Warmblood) but not in light horse breeds selected for speed or
      racing performance (Standardbred, Thoroughbred, and Quarter horse) or in ponies
      (Icelandic horses and Shetland pony). The results will facilitate future studies
      of the possible functional significance of PRKAG3 polymorphisms in horses.

PMID- 14970706
TI  - Homologous fission event(s) implicated for chromosomal polymorphisms among five
      species in the genus Equus.
AB  - The genus Equus is unusual in that five of the ten extant species have documented
      centric fission (Robertsonian translocation) polymorphisms within their
      populations, namely E. hemionus onager, E. hemionus kulan, E. kiang, E. africanus
      somaliensis, and E. quagga burchelli. Here we report evidence that the
      polymorphism involves the same homologous chromosome segments in each species,
      and that these chromosome segments have homology to human chromosome 4 (HSA4).
      Bacterial artificial chromosome clones containing equine genes SMARCA5 (ECA2q21
      homologue to HSA4q31. 21) and UCHL1 (ECA3q22 homologue to HSA4p13) were mapped to
      a single metacentric chromosome and two unpaired acrocentrics by FISH mapping for
      individuals possessing odd numbers of chromosomes. These data suggest that the
      polymorphism is either ancient and conserved within the genus or has occurred
      recently and independently within each species. Since these species are separated
      by 1-3 million years of evolution, this polymorphism is remarkable and worthy of
      further investigations.

PMID- 14970707
TI  - FISH analysis comparing genome organization in the domestic horse (Equus
      caballus) to that of the Mongolian wild horse (E. przewalskii).
AB  - Przewalski's wild horse (E. przewalskii, EPR) has a diploid chromosome number of
      2n = 66 while the domestic horse (E. caballus, ECA) has a diploid chromosome
      number of 2n = 64. Discussions about their phylogenetic relationship and
      taxonomic classification have hinged on comparisons of their skeletal morphology,
      protein and mitochondrial DNA similarities, their ability to produce fertile
      hybrid offspring, and on comparison of their chromosome morphology and banding
      patterns. Previous studies of GTG-banded karyotypes suggested that the
      chromosomes of both equids were homologous and the difference in chromosome
      number was due to a Robertsonian event involving two pairs of acrocentric
      chromosomes in EPR and one pair of metacentric chromosomes in ECA (ECA5). To
      determine which EPR chromosomes were homologous to ECA5 and to confirm the
      predicted chromosome homologies based on GTG banding, we constructed a
      comparative gene map between ECA and EPR by FISH mapping 46 domestic horse
      derived BAC clones containing genes previously mapped to ECA chromosomes. The
      results indicated that all ECA and EPR chromosomes were homologous as predicted
      by GTG banding, but provide new information in that the EPR acrocentric
      chromosomes EPR23 and EPR24 were shown to be homologues of the ECA metacentric
      chromosome ECA5.

PMID- 14970708
TI  - Genetic variation in Przewalski's horses, with special focus on the last wild
      caught mare, 231 Orlitza III.
AB  - In our continuing efforts to document genetic diversity in Przewalski's horses
      and relatedness with domestic horses, we report genetic variation at 22 loci of
      blood group and protein polymorphisms and 29 loci of DNA (microsatellite)
      polymorphisms. The loci have been assigned by linkage or synteny mapping to 20
      autosomes and the X chromosome of the domestic horse (plus four loci unassigned
      to a chromosome). With cumulative data from tests of 568 Przewalski's horses
      using blood, hair or tooth samples, no species-defining markers were identified,
      however a few markers were present in the wild species but not in domestic
      horses. Inheritance patterns and linkage relationships reported in domestic
      horses appeared to be conserved in Przewalski's horses. A derived type for the
      last wild caught mare 231 Orlitza III provided evidence for markers apparently
      not found in (or not currently available by descent from) the other species
      founders that were captured at the end of the nineteenth century. This
      information has been critical to the development of parentage analyses in the
      studbook population of Przewalski's horses at Askania Nova, at one time the
      largest herd of captive animals and the source of stock for reintroduction
      efforts. Some horses in the study showed genetic incompatibilities with their
      sire or dam, contradicting published studbook information. In many cases
      alternative parentage could be assigned from living animals. To assist in
      identification of correct parentage, DNA marker types for deceased horses were
      established from archived materials (teeth) or derived from offspring. Genetic
      markers were present in pedigreed animals whose origin could not be accounted for
      from founders. Genetic distance analysis of erythrocyte protein, electrophoretic
      and microsatellite markers in Przewlaski's horses and ten breeds of domestic
      horse place the Przewalski's horse as an outgroup to domestic horses,
      introgression events from domestic horses not withstanding.

PMID- 14970709
TI  - Karyotypic relationships of horses and zebras: results of cross-species
      chromosome painting.
AB  - Complete sets of chromosome-specific painting probes, derived from flow-sorted
      chromosomes of human (HSA), Equus caballus (ECA) and Equus burchelli (EBU) were
      used to delineate conserved chromosomal segments between human and Equus
      burchelli, and among four equid species, E. przewalskii (EPR), E. caballus, E.
      burchelli and E. zebra hartmannae (EZH) by cross-species chromosome painting.
      Genome-wide comparative maps between these species have been established. Twenty
      two human autosomal probes revealed 48 conserved segments in E. burchelli. The
      adjacent segment combinations HSA3/21, 7/16p, 16q/19q, 14/15, 12/22 and 4/8,
      presumed ancestral syntenies for all eutherian mammals, were also found conserved
      in E. burchelli. The comparative maps of equids allow for the unequivocal
      characterization of chromosomal rearrangements that differentiate the karyotypes
      of these equid species. The karyotypes of E. przewalskii and E. caballus differ
      by one Robertsonian translocation (ECA5 = EPR23 + EPR24); numerous Robertsonian
      translocations and tandem fusions and several inversions account for the
      karyotypic differences between the horses and zebras. Our results shed new light
      on the karyotypic evolution of Equidae.

PMID- 14970710
TI  - Digging up the canine genome--a tale to wag about.
AB  - There is incredible morphological and behavioral diversity among the hundreds of
      breeds of the domestic dog, CANIS FAMILIARIS. Many of these breeds have come into
      existence within the last few hundred years. While there are obvious phenotypic
      differences among breeds, there is marked interbreed genetic homogeneity. Thus,
      study of canine genetics and genomics is of importance to comparative genomics,
      evolutionary biology and study of human hereditary diseases. The most recent
      version of the map of the canine genome is comprised of 3,270 markers mapped to
      3,021 unique positions with an average intermarker distance of approximately 1
      Mb. The markers include approximately 1,600 microsatellite markers, about 1,000
      gene-based markers, and almost 700 bacterial artificial chromosome-end markers.
      Importantly, integration of radiation hybrid and linkage maps has greatly
      enhanced the utility of the map. Additionally, mapping the genome has led
      directly to characterization of microsatellite markers ideal for whole genome
      linkage scans. Thus, workers are now able to exploit the canine genome for a wide
      variety of genetic studies. Finally, the decision to sequence the canine genome
      highlights the dog's evolutionary and physiologic position between the mouse and
      human and its importance as a model for study of mammalian genetics and human
      hereditary diseases.

PMID- 14970711
TI  - Isolation and chromosomal assignment of canine genomic BAC clones representing 25
      cancer-related genes.
AB  - An extensive number of genes have been implicated in the initiation and
      progression of human cancers, aiding our understanding of the genetic aetiology
      of this highly heterogeneous disease. In order to facilitate extrapolation of
      such information between species, we have isolated and physically mapped the
      canine orthologues of 25 well-characterised human cancer-related genes. The
      identity of PCR products representing each canine gene marker was first confirmed
      by DNA sequencing analysis. Each product was then radiolabelled and used to
      screen a genomic BAC library for the domestic dog. The chromosomal location of
      each positive clone in the canine karyotype was determined by fluorescence in
      situ hybridisation (FISH) onto canine metaphase preparations. Of the 25 genes,
      the FISH localisation of 21 correlated fully with that expected on the basis of
      known regions of conserved synteny between the human and canine genomes. Three
      correlated less closely, and the chromosomal location of the remaining marker
      showed no apparent correlation with current comparative mapping data. In addition
      to generating useful comparative mapping information, this panel of markers will
      act as a valuable resource for detailed study of candidate genes likely to be
      involved in tumourigenesis, and also forms the basis of a canine cancer-gene
      genomic microarray currently being developed for the study of unbalanced genomic
      aberrations in canine tumours.

PMID- 14970712
TI  - A canine cancer-gene microarray for CGH analysis of tumors.
AB  - As with many human cancers, canine tumors demonstrate recurrent chromosome
      aberrations. A detailed knowledge of such aberrations may facilitate diagnosis,
      prognosis and the selection of appropriate therapy. Following recent advances
      made in human genomics, we are developing a DNA microarray for the domestic dog,
      to be used in the detection and characterization of copy number changes in canine
      tumors. As a proof of principle, we have developed a small-scale microarray
      comprising 87 canine BAC clones. The array is composed of 26 clones selected from
      a panel of 24 canine cancer genes, representing 18 chromosomes, and an additional
      set of clones representing dog chromosomes 11, 13, 14 and 31. These chromosomes
      were shown previously to be commonly aberrant in canine multicentric malignant
      lymphoma. Clones representing the sex chromosomes were also included. We outline
      the principles of canine microarray development, and present data obtained from
      microarray analysis of three canine lymphoma cases previously characterized using
      conventional cytogenetic techniques.

PMID- 14970713
TI  - Identification of isoforms and RH mapping of canine KIT.
AB  - The proto-oncogene, C-KIT (KIT), encodes a tyrosine kinase receptor, and
      mutations in this gene are causative for several mammalian diseases, including
      cancer and a form of pigmentation-associated hereditary deafness. Our
      laboratories are interested in a form of hereditary deafness that is associated
      with abnormalities in pigmentation and is common in the Dalmatian. Thus, KIT is
      being analyzed as a candidate gene for deafness in this breed. In addition to our
      interest in deafness, we are involved in mapping gene loci in the canine genome.
      Reported here is the identification of two isoforms of canine C-kit and radiation
      hybrid mapping of KIT to CFA13.

PMID- 14970714
TI  - Comparative chromosomal localization of the canine-derived BAC clones containing
      LEP and IGF1 genes in four species of the family Canidae.
AB  - In the present report we show the chromosomal localization of two BAC clones,
      carrying the leptin (LEP) and insuline-like growth factor 1 (IGF1) genes,
      respectively, in four species belonging to the family Canidae: the dog, red fox,
      arctic fox and the Chinese raccoon dog. The assignments are in agreement with
      earlier data obtained from comparative chromosome painting for the dog, red fox
      and arctic fox.

PMID- 14970715
TI  - Development of a cytogenetic map for the Chinese raccoon dog (Nyctereutes
      procyonoides procyonoides) and the arctic fox (Alopex lagopus) genomes, using
      canine-derived microsatellite probes.
AB  - New chromosomal assignments of canine-derived cosmid clones containing
      microsatellites to the Chinese raccoon dog and arctic fox genomes are presented
      in the study. The localizations are in agreement with data obtained from
      comparative chromosome painting experiments between the dog and arctic fox
      genomes. However, paracentric inversions have been detected by comparing the loci
      order in canid karyotypes. The number of physically mapped loci increased to
      thirty-five both in the Chinese raccoon dog and in the arctic fox. Furthermore,
      the present status of the cytogenetic map of the Chinese raccoon dog and arctic
      fox is presented in this study.

PMID- 14970716
TI  - Radiation hybrid mapping of 304 novel microsatellites in the domestic cat genome.
AB  - Effective utilization of the domestic cat as an animal model for hereditary and
      infectious disease requires the development and implementation of high quality
      gene maps incorporating microsatellites and conserved coding gene markers.
      Previous feline linkage and radiation hybrid maps have lacked sufficient
      microsatellite coverage on all chromosomes to make effective use of full genome
      scans. Here we report the isolation and genomic mapping of 304 novel polymorphic
      repeat loci in the feline genome. The new loci were mapped in the domestic cat
      radiation hybrid panel using an automated fluorescent TAQ-Man based assay. The
      addition of these 304 microsatellites brings the total number of microsatellites
      mapped in the feline genome to 580, and the total number of loci placed onto the
      RH map to 1,126. Microsatellites now span every autosome with an average spacing
      of roughly one polymorphic STR every five centimorgans, and full genome coverage
      of one marker every 2.7 megabases. These loci now provide a useful tool for
      undertaking full-genome scans to identify genes associated with phenotypes of
      interest, such as those relating to hereditary disease, coat color, patterning
      and morphology. These resources can also be extended to the remaining 36 species
      of the cat family for population genetic and evolutionary genomic analyses.

PMID- 14970717
TI  - Integration of animal linkage and BAC contig maps using overgo hybridization.
AB  - The alignment of genome linkage maps, defined primarily by segregation of
      sequence-tagged site (STS) markers, with BAC contig physical maps and full genome
      sequences requires high throughput mechanisms to identify BAC clones that contain
      specific STS. A powerful technique for this purpose is multi-dimensional
      hybridization of "overgo" probes. The probes are chosen from available STS
      sequence data by selecting unique probe sequences that have a common melting
      temperature. We have hybridized sets of 216 overgo probes in subset pools of 36
      overgos at a time to filter-spotted chicken BAC clone arrays. A four-dimensional
      pooling strategy, including one degree of redundancy, has been employed. This
      requires 24 hybridizations to completely assign BACs for all 216 probes. Results
      to date are consistent with about a 10% failure rate in overgo probe design and a
      15-20% false negative detection rate within a group of 216 markers. Three
      complete rounds of overgo hybridization, each to sets of about 39,000 BACs
      (either BAMHI or ECORI partial digest inserts) generated a total of 1853 BAC
      alignments for 517 mapped chicken genome STS markers. These data are publicly
      available, and they have been used in the assembly of a first generation BAC
      contig map of the chicken genome.

PMID- 14970718
TI  - Reversal and convergence in marsupial chromosome evolution.
AB  - The karyotypes of marsupial species are characterized by their relatively low
      number of chromosomes, and their conservation. Most species have diploid numbers
      lying between the two modes, 2n = 14 and 2n = 22, but the karyotype of
      Aepyprymnus rufescens is exceptional in containing 2n = 32 chromosomes. Many
      differences in diploid number between marsupial species can be accounted for by
      particular fissions and fusions, which are easy to detect because of the low
      numbers of chromosomes in each karyotype. This should be a system in which it is
      possible to detect reversals and repeated chromosome rearrangements. We have used
      chromosome-specific paints derived from A. RUFESCENS to compare the karyotypes of
      eight marsupial species, representing closely and distantly related taxa, to
      trace chromosome change during evolution, and especially to detect reversals and
      convergence. From these and other painting comparisons, we conclude that there
      have been at least three reversals of fusions by fissions, and at least three
      fusions or fissions that have occurred independently in different lineages.

PMID- 14970719
TI  - Chicken genome sequence: a centennial gift to poultry genetics.
AB  - A draft sequence of the chicken genome will be available by early 2004. This
      event conveniently marks the start of the second century of poultry genetics,
      coming 100 years after the use of the chicken to demonstrate Mendelian
      inheritance in animals by William Bateson. How will the second, post-genomic
      century of poultry genetics differ from the first? A whole genome shotgun (WGS)
      approach is being used to obtain the chicken sequence, with the goal of
      generating approximately six-fold coverage of the genome. Bacterial artificial
      chromosome (BAC) and fosmid clone end sequences, along with a BAC contig map
      integrated with genetic linkage and radiation hybrid maps, will form the platform
      for assembly of the WGS data. Rapid progress in global analysis of chicken gene
      expression patterns is also being made. Comparative genomics will link these new
      discoveries to the knowledge base for all other animal species. It's hoped that
      the genome sequence will also provide common ground on which to unite studies of
      the chicken as a model species with those aimed at agriculturally-relevant
      applications. The current status of chicken genomics will be assessed with
      projections for its near and long term future.

PMID- 14970720
TI  - Integration of chicken genomic resources to enable whole-genome sequencing.
AB  - Different genomic resources in chicken were integrated through the Wageningen
      chicken BAC library. First, a BAC anchor map was created by screening this
      library with two sets of markers: microsatellite markers from the consensus
      linkage map and markers created from BAC end sequencing in chromosome walking
      experiments. Second, HINdIII digestion fingerprints were created for all BACs of
      the Wageningen chicken BAC library. Third, cytogenetic positions of BACs were
      assigned by FISH. These integrated resources will facilitate further chromosome
      walking experiments and whole-genome sequencing.

PMID- 14970721
TI  - Identification of chicken lymphocyte antigen 6 complex, locus E (LY6E, alias
      SCA2) as a putative Marek's disease resistance gene via a virus-host protein
      interaction screen.
AB  - Marek's disease virus (MDV) is a naturally occurring oncogenic avian herpesvirus
      that causes neurological disorders and T cell lymphoma disease in domestic
      chickens. Identification and functional characterization of the individual
      factors involved in Marek's disease (MD) resistance or pathogenesis will enhance
      our understanding of MDV pathogenesis and further genetic improvement of
      chickens. To study the genetic basis for resistance to MD, a strategy that
      combined protein-protein interaction screens followed by linkage analysis was
      performed. The MDV protein US10 was used as the bait in an E. COLI two-hybrid
      screening of a cDNA library derived from activated splenic T cells. The chicken
      LY6E, also known as SCA2 and TSA1, was found to specifically interact with US10.
      This interaction was confirmed by an in vitro protein-binding assay. Furthermore,
      LY6E was found to be significantly associated with MD traits in an MD resource
      population comprised of commercial chickens. Previously, LY6E was implicated in
      two independent DNA microarray experiments evaluating differential gene
      expression following MDV infection. Given that LY6E is involved in T cell
      differentiation and activation, we suggest that LY6E is a candidate gene for MD
      resistance and deserves further investigation on its role in MDV pathogenesis,
      especially with respect to the binding of US10.

PMID- 14970722
TI  - The chicken telomerase RNA gene: conservation of sequence, regulatory elements
      and synteny among viral, avian and mammalian genomes.
AB  - Telomerase RNA (TR) is essential for telomerase activity and the maintenance of
      telomere length in proliferating cell populations. The objective of the present
      research was to define the cytogenetic and molecular genomic organization of
      chicken TR (chTR). The chTR exists as a single copy gene (TERC, alias TR),
      mapping to chromosome 9 (GGA9). The loci on the q arm of GGA9 map to three
      chromosomes in human with five of the nine GGA9q loci mapping to HSA3q.
      Sequencing of the chTERC locus (3,763 bp) from the UCD 001 genome (Red Jungle
      Fowl) included: 604 bp 5', 465 coding, and 2,694 bp 3' (from -604 to +3159).
      Sequence analysis included homology searches conducted on several levels
      including comparisons among different chicken genotypes, Marek's disease virus
      (MDV) sequences, plus human and murine. We provide evidence for distal 5' and 3'
      sequence homology between chTERC and the MDV genome among other known regions of
      homology (promoter and coding), elaborate on 5' transcription factor binding
      motifs among the various genomes as well as show type and number of TERT-related
      motifs 3' of chicken TR (e.g., Sp1, c-Myb, c-Myc, AP2, among others). Surrounding
      the gene are more than 25 Sp1 sites, over 20 oncogene transcription factor
      binding motifs and numerous hormonal and other specialized binding motifs.
      Knowledge of 5' and 3' chTERC regulatory elements will be useful for
      investigating normal control mechanisms during growth and development as well as
      investigating the potential for dysregulation of this important gene during
      oncogenesis, especially among different genotypes.

PMID- 14970723
TI  - Dynamics of telomere erosion in transformed and non-transformed avian cells in
      vitro.
AB  - Although vertebrate telomeres are highly conserved, telomere dynamics and
      telomerase profiles vary among species. The objective of the present study was to
      examine telomerase activity and telomere length profiles of transformed and non
      transformed avian cells in vitro. Non-transformed chicken embryo fibroblasts
      (CEFs) showed little or no telomerase activity from the earliest passages through
      senescence. Unexpectedly, a single culture of particularly long-lived senescent
      CEFs showed telomerase activity after over 250 days in culture. Transformed avian
      lines (six chicken, two quail and one turkey) and tumor samples (two chicken)
      exhibited telomerase activity. Telomere length profiles of non-transformed CEF
      cultures derived from individual embryos of an inbred line (UCD 003) exhibited
      cycles of shortening and lengthening with a substantial net loss of telomeric DNA
      by senescence. The telomere length profiles of several transformed cell lines
      resembled telomere length profiles of senescent CEFs in that they exhibited
      little of the typical smear of terminal restriction fragments (TRFs) suggesting
      that these transformed cells may possess a reduced amount of telomeric DNA. These
      results show that avian telomerase activity profiles are consistent with the
      telomerase activity profiles of human primary and transformed cells. Further,
      monitoring of telomere lengths of primary cells provides evidence for a dynamic
      series of changes over the lifespan of any specific cell culture ultimately
      resulting in net telomeric DNA loss by senescence.

PMID- 14970724
TI  - Chromosome homology between chicken (Gallus gallus domesticus) and the red-legged
      partridge (Alectoris rufa); evidence of the occurrence of a neocentromere during
      evolution.
AB  - Chromosome-specific paints from macrochromosomes 1-9 and Z of the chicken were
      hybridised to metaphases of the red-legged partridge and revealed no inter
      chromosomal rearrangements. The results from chromosome painting are similar to
      previous studies on the Japanese quail but different from findings in guinea fowl
      and several species of pheasant. The difference in centromere position in chicken
      and partridge chromosome 4, previously assumed to be the result of an inversion,
      was confirmed. However, FISH mapping of BAC clones from chicken chromosome 4
      revealed that the order of loci was the same in both species, indicating the
      occurrence of a neocentromere during divergence.

PMID- 14970725
TI  - Allelic variation and genetic linkage of avian microsatellites in a new turkey
      population for genetic mapping.
AB  - Efforts to build a comprehensive genetic linkage map for the turkey (Meleagris
      gallopavo) have focused on development of genetic markers and experimental
      resource families. In this study, PCR amplification was attempted for 772
      microsatellite markers that had been previously developed for three avian species
      (chicken, quail and turkey). Allelic polymorphism at 410 markers (53.1% of total
      examined) was determined by genotyping ten individuals (six F1 parents and four
      grandparents) in a new resource population specifically developed for genetic
      linkage mapping. Of these 410 markers, 109 (26.6%) were polymorphic in the tested
      individuals, with an average of 2.3 alleles per marker. Higher levels of
      polymorphism were found for the turkey-specific markers (61.1%) than for the
      chicken (22.7%) or quail-specific markers (33.3%). To test the fidelity of the
      matings, demonstrate the power of these families for linkage analysis, and
      determine genetic linkage relationships, 86 polymorphic markers were genotyped
      for up to 224 birds including founder grandparents, parents and F2 progeny.
      Linkage relationships for many of the chicken markers elucidated in the turkey
      were comparable to those observed in the chicken. These data demonstrate that the
      new UMN/NTBF resource population will provide a solid foundation for constructing
      a comparative genetic map of the turkey.

PMID- 14970726
TI  - Myosin light chain genes in the turkey (Meleagris gallopavo).
AB  - Myosin light chains associate with the motor protein myosin and are believed to
      play a role in the regulation of its actin-based ATPase activity. Myosin light
      chain cDNA clones from the turkey (Meleagris gallopavo) were isolated and
      sequenced. One sequence corresponded to an alternative transcript, the skeletal
      muscle essential light chain (MYL1 isoform 1) and a second to the smooth muscle
      isoform of myosin light chain (MYL6). The DNA and predicted amino acid sequences
      of both light chain genes were compared to that of the chicken. Based on the cDNA
      sequence, oligonucleotide primers were designed to amplify genomic DNA from six
      of the seven introns of the MYL1 gene. Approximately 5 kb of DNA was sequenced
      (introns and 3' UTR) and evaluated for the presence of single nucleotide
      polymorphisms (SNPs). SNPs were verified by sequencing common intron regions from
      multiple individuals and three polymorphisms were used to genotype pedigreed
      families. MYL1 is assigned to a turkey linkage group that corresponds to a region
      of chicken chromosome 7 (GGA7). The results of this study provide genomic
      reagents for comparative studies of avian muscle components and muscle biology.

PMID- 14970728
TI  - Abstracts of the 13th North American Colloquium on Animal Cytogenetics and Gene
      Mapping. July 13-17, 2003, Louisville, Kentucky, USA.

PMID- 14970729
TI  - Interaction of adolescent anthropometric characteristics and family history on
      breast cancer risk in a Historical Cohort Study of 426 families (USA).
AB  - OBJECTIVE: To determine whether the association of adolescent anthropometric
      characteristics with breast cancer is modified by a family history of the
      disease. METHODS: These interactions were evaluated in a historical cohort of 426
      families of breast cancer probands diagnosed between 1944 and 1952 at the
      University of Minnesota. The occurrence of breast cancer and the measurement of
      risk factors in sisters, daughters, granddaughters, nieces and marry-ins was
      determined through telephone interviews and mailed questionnaires conducted from
      1991-1996. Cox proportional hazards regression, accounting for age, birth cohort,
      adult body mass index (BMI), and clustering within families, was used to estimate
      relative risks (RR) and 95% confidence intervals (CIs) of breast cancer. RESULTS:
      Among 4632 women from 426 families available for analysis, there were 175 breast
      cancers. There was a strong interaction between degree of relationship to proband
      and relative weight at age 12 on breast cancer risk ( p < 0.001). Among sisters
      and daughters of the probands, risk of breast cancer was slightly increased in
      those with below average weight at age 12 (RR = 1.55; 95% CI = 0.66-3.64), and
      strongly increased in those with above average weight (RR = 4.25; 95% CI = 1.71
      10.5), compared to those with average weight. In contrast, among marry-ins, there
      was a weak positive association for those with below average weight at age 12 (RR
      = 1.61; 95% CI = 0.91-2.83), while there was an inverse association for above
      average weight (RR = 0.75; 95% CI = 0.26-2.16), compared to those with average
      weight. There were no significant interactions between degree of relationship to
      proband and height ( p = 0.55), weight at age 18 ( p = 0.22) and BMI at age 18 (
      p = 0.63) on breast cancer risk. CONCLUSIONS: Family history appears to modify
      the effect of obesity in early adolescence on subsequent breast cancer risk, and
      may identify differing etiologic pathways.

PMID- 14970730
TI  - Foods, nutrients and prostate cancer.
AB  - OBJECTIVE: To examine the risk of prostate cancer associated with foods and
      nutrients, including individual fatty acids and carotenoids. METHODS: Population
      based case-control study of 858 men aged <70 years at diagnosis with
      histologically confirmed prostate cancer of Gleason Grade 5 or greater, and 905
      age-frequency-matched men, selected at random from the electoral rolls. Dietary
      intakes were assessed with a 121-item food frequency questionnaire. RESULTS:
      Inverse associations with prostate cancer were observed for (Odds ratio, OR, 95%
      confidence intervals, 95% CI for tertile III compared with tertile I) allium
      vegetables 0.7, 0.5-0.9; p trend 0.01, tomato-based foods 0.8, 0.6-1.0; p trend
      0.03 and total vegetables 0.7, 0.5-1.0; p trend 0.04. Margarine intake was
      positively associated with prostate cancer 1.3, 1.0-1.7; p trend 0.04. The only
      statistically significant associations observed with nutrients were weak inverse
      associations for palmitoleic acid ( p trend 0.04), fatty acid 17:1 ( p trend
      0.04), and 20:5 n-6 ( p trend 0.05); and a non-significant trend for oleic acid (
      p trend 0.09). Neither total, nor beverage-specific, intake of alcohol was
      associated with risk. CONCLUSIONS: Based on these findings, diets rich in olive
      oil (a source of oleic acid), tomatoes and allium vegetables might reduce the
      risk of prostate cancer.

PMID- 14970727
TI  - Sequence analysis of a rainbow trout cDNA library and creation of a gene index.
AB  - Expressed sequence tag (EST) projects have produced extremely valuable resources
      for identifying genes affecting phenotypes of interest. A large-scale EST
      sequencing project for rainbow trout was initiated to identify and functionally
      annotate as many unique transcripts as possible. Over 45,000 5' ESTs were
      obtained by sequencing clones from a single normalized library constructed using
      mRNA from six tissues. The production of this sequence data and creation of a
      rainbow trout Gene Index eliminating redundancy and providing annotation for
      these sequences will facilitate research in this species.

PMID- 14970731
TI  - Subjective and objective risk of colorectal cancer (UK).
AB  - OBJECTIVE: The aim of this study was to see whether individuals who perceive
      their risk for developing colorectal cancer (CRC) as lower than average are found
      to be at lower risk as determined by findings at flexible sigmoidoscopy (FS)
      screening. METHODS: Participants (n = 10,551) were men and women aged 55-64 years
      from a subset of participants in the UK FS Trial. Self-report questionnaires
      assessed perceived comparative risk of developing bowel cancer prior to
      participants being invited to attend FS screening. Objective risk was judged from
      polyp status during the FS test. RESULTS: A very modest relationship was found
      between risk judgments and actual risk with 77% of 'optimists' having negative
      findings compared to 71% of 'pessimists'. More pessimists (14%) had an adenoma
      compared to optimists (11%). Compared to pessimists the odds of optimists
      actually being at lower risk of CRC equaled 0.70 (0.57, 0.86). CONCLUSIONS: The
      results suggest that people may have a limited ability to assess their risk of
      developing CRC. Health professionals should not assume that individuals have an
      accurate perception of their risk for cancer. Increasing people's ability to
      accurately perceive their risk may encourage more appropriate cancer preventive
      behavior.

PMID- 14970732
TI  - Adolescent smoking and trends in lung cancer incidence among young adults in
      Norway 1954-1998.
AB  - OBJECTIVE: To describe the national trends in lung cancer incidence among young
      adults and the relationship to adolescent smoking. METHODS: Between 1954 and
      1998, a total of 1108 non-carcinoid lung cancers were reported to the Cancer
      Registry of Norway in individuals aged 20-44 years. Temporal variations were
      studied in age and sex specific rates, in age-adjusted rates, and by means of age
      period-cohort modelling. The association between cancer incidence and smoking
      prevalence was evaluated. RESULTS: The lung cancer incidence rate among women
      aged 40-44 in Norway continued to increase into the most recent time interval
      (1994-1998) whereas the rate among men aged 40-44 was essentially constant after
      1970. Consequently, lung cancer incidence rates converged among male and female
      young adults. Lung cancer incidence rates at age 40-44 were highly correlated
      with smoking prevalence at age 15-19 in males ( r = 0.88) and females ( r = 0.82)
      within the same birth cohort. CONCLUSIONS: The lung cancer incidence rate in
      young Norwegian women now equals that of men. The risk at age 40-44 was closely
      associated with teenage smoking, indicating that duration and age of onset are
      important.

PMID- 14970733
TI  - Obesity and cancer risk among white and black United States veterans.
AB  - BACKGROUND: Obesity has been linked to excess risk for many cancers, but the
      evidence remains tenuous for some types. Although the prevalence of obesity
      varies by race, few studies of obesity-related cancer risk have included non
      white subjects. METHODS: In a large cohort of male US veterans (3,668,486 whites;
      832,214 blacks) hospitalized with a diagnosis of obesity between 1969 and 1996,
      we examined risk for all major cancer sites and subsites. Person-years accrued
      from the date of first obesity diagnosis until the occurrence of a first cancer,
      death, or the end of the observation period (September 30, 1996). We calculated
      age- and calendar-year adjusted relative risks (RR) and 95% confidence intervals
      (CI) for cancer among white and black veterans, comparing obese men to men
      hospitalized for other reasons, with obesity status as time-dependent. For
      selected cancers, we performed additional analyses stratified by specific medical
      conditions related to both obesity and risk of those cancers. To determine
      whether obesity-related cancer risks differed significantly between white and
      black men, we evaluated heterogeneity of risk for each cancer site. RESULTS:
      Among white veterans, risk was significantly elevated for several cancers,
      including cancers of the lower esophagus, gastric cardia, small intestine, colon,
      rectum, gallbladder and ampulla of vater, male breast, prostate, bladder,
      thyroid, and connective tissue, and for malignant melanoma, multiple myeloma,
      chronic lymphocytic leukemia (CLL), and acute myeloid leukemia (AML). Excess
      risks initially observed for cancers of the liver and pancreas persisted among
      men without a history of diabetes or alcoholism. Among black veterans, risks were
      significantly elevated for cancers of the colon, extrahepatic bile ducts,
      prostate, thyroid, and for malignant melanoma, multiple myeloma, CLL and AML.
      CONCLUSIONS: Obese men are at increased risk for several major cancers as well as
      a number of uncommon malignancies, a pattern generally similar for white and
      black men. Due to the increasing prevalence of obesity and overweight worldwide,
      it is important to clarify the impact of excess body weight on cancer and to
      elucidate the mechanisms involved.

PMID- 14970734
TI  - Serum levels of sex hormones and breast cancer risk in premenopausal women: a
      case-control study (USA).
AB  - High levels of serum estrogens and androgens have been convincingly linked with
      an increased risk of breast cancer among postmenopausal women. By contrast, the
      role of blood levels of these hormones in the etiology of premenopausal breast
      cancer is not well understood. In a case-control study, we sought to examine
      associations between levels of serum estradiol, sex-hormone binding globulin
      (SHBG), dehydroepiandrosterone (DHEA), testosterone, androstenedione and
      progesterone and risk of premenopausal breast cancer. Cases of breast cancer
      under age 45 were identified using rapid ascertainment systems in Seattle/Puget
      Sound, Washington and control subjects were identified from the same area through
      random digit dialing methods. A total of 169 eligible breast cancer cases and 195
      control subjects donated blood (either before or six or more weeks after surgery)
      and were interviewed using a standardized questionnaire. The fully adjusted risk
      ratios and 95% confidence intervals for the highest versus lowest tertiles of
      estradiol, according to menstrual cycle phase, were 3.10 (0.8-12.7) for early
      follicular, 0.54 (0.2-1.7) for late follicular and 0.60 (0.3-1.4) for luteal.
      Risks for highest versus lowest quartiles of SHBG and androgens were 0.81 (0.4
      1.6) for SHBG, 2.42 (1.1-5.2) for DHEA, 1.12 (0.6-2.5) for testosterone, and 1.33
      (0.6-2.8) for androstenedione. For luteal progesterone, the RR for the highest
      versus lowest tertile was 0.55 (0.2-1.4). In summary, we did not find a
      convincing association between serum SHBG, estradiol, testosterone or
      androstenedione and premenopausal breast cancer risk. Observed differences
      between cases and controls subjects in serum levels of DHEA and luteal phase
      progesterone should be investigated further in large prospective studies.

PMID- 14970735
TI  - A cohort study of cancer mortality among Biology Research Laboratory workers in
      The Netherlands.
AB  - OBJECTIVE: To examine cancer mortality among persons employed in biology research
      institutes. METHOD: A historical cohort study was undertaken in the Netherlands.
      The cohort, comprising 7307 laboratory workers employed by the four participating
      institutes between 1960 and 1992, was followed for mortality from 1960 to 1995
      (median follow-up time 16.5 years). Causes of death were obtained for 98% of all
      deaths. Cancer mortality in the cohort was compared with that in the general
      population by computation of the standardized mortality ratio (SMR). The Cox
      proportional hazards model was used to compare cancer mortality among laboratory
      workers with that in an internal reference population consisting of unexposed
      research personnel (n = 2,404). RESULTS: All-cause mortality among laboratory
      workers was significantly lower than that in the general population. Total cancer
      mortality and lung cancer mortality were also significantly decreased (SMR = 0.8;
      95% confidence interval CI = 0.7-0.9 and SMR = 0.7; 95% CI = 0.6-0.9),
      respectively. However, when compared to the internal reference population,
      laboratory workers had a slightly increased cancer mortality (relative risk (RR)
      = 1.3 95% CI = 0.9-1.9). Among men, a 2.5-fold (95% CI = 1.0-6.3) increase of
      lung cancer mortality was observed which could not be explained by differences in
      smoking habits. Lung cancer mortality increased with longer follow-up. Results
      with regard to a priori defined fields of research showed significantly increased
      cancer mortality (in particular from lung cancer) for men working in genetics (RR
      = 3.8), virology (RR = 4.1) and plant physiology (RR = 2.1). CONCLUSION:
      Laboratory workers have a favorable cancer mortality pattern as compared to the
      general population. However, this favorable pattern disappears when a comparison
      is made with a control group of unexposed research personnel. The excess lung
      cancer mortality among male laboratory workers was concentrated in certain fields
      of research, which warrants further research to identify specific exposures
      related to the increased risk.

PMID- 14970736
TI  - Flavonoids, vitamin C and adenocarcinoma of the stomach.
AB  - OBJECTIVE: To examine the role of six flavonoid classes (flavanones, flavan-3
      ols, flavonols, flavones, anthocyanidins and isoflavones) and vitamin C in the
      aetiology of stomach cancer. METHODS: Case-control study undertaken in Greece in
      the 1980s. Dietary information was obtained from 110 patients with incident
      stomach adenocarcinoma and 100 control patients. Flavonoid estimates were based
      on the recently released database of the US Department of Agriculture. RESULTS:
      In models including sociodemographic variables, energy intake, vegetables, fruits
      and, alternatively, vitamin C the six flavonoid classes, only flavanones and
      vegetables remained significantly inversely associated with stomach cancer risk.
      The odds ratio (95% confidence intervals) per one standard deviation increase of
      intake of flavanones was 0.55 (0.31-0.96) whereas for vitamin C it was 1.05 (0.46
      2.41). When fruits and vegetables were not adjusted for, both vitamin C and
      several flavonoid categories were inversely associated with stomach cancer risk,
      but these associations could be attributed to other compounds in these foods.
      CONCLUSIONS: Among the major flavonoid classes studied, only flavanone intake is
      inversely associated with stomach cancer risk and could account for the apparent
      protective effect of fruit intake against this form of cancer. Additional
      factors, however, are likely to be involved in the consistent protection conveyed
      by vegetables.

PMID- 14970737
TI  - Adolescent diet and risk of breast cancer.
AB  - OBJECTIVES: To investigate the components of adolescent diet that may influence
      risk of breast cancer as an adult. METHODS: Retrospective cohort study among
      47,355 participants in the Nurses Health Study II who answered a 131-item food
      frequency questionnaire about diet during high school. Cox proportional hazards
      regression was used to estimate relative risks and 95% confidence intervals among
      incident cases of breast cancer between 1989 (inception of the study) and 1998
      (when high school diet was assessed). RESULTS: Intakes of fat and fiber were not
      significantly related to risk of breast cancer in multivariate analysis, but
      increased intake of vegetable fat ( Q (5) versus Q (1) multivariate RR = 0.58,
      95% CI (0.38-0.86); test for trend p = 0.005) and vitamin E ( Q (5) versus Q (1)
      multivariate RR = 0.61, 95% CI (0.42-0.89); test for trend p = 0.003) were
      associated with a lower risk. A higher dietary glycemic index ( Q (5) versus Q
      (1) multivariate RR = 1.47, 95% CI (1.04-2.08); test for trend p = 0.01) was
      associated with increased risk of breast cancer. CONCLUSIONS: The apparent
      protective effects of vegetable fat and vitamin E and adverse effect of high
      glycemic foods on risk of breast cancer need confirmation in prospective
      analyses.

PMID- 14970738
TI  - Sedentary behaviours and epithelial ovarian cancer risk.
AB  - OBJECTIVE: To investigate the effects of sedentary behaviours on the risk of
      epithelial ovarian cancer. METHODS: A case-control study was conducted in China
      during 1999-2000. Cases were 254 patients with histologically confirmed
      epithelial ovary cancer. The 652 controls comprised 340 hospital visitors, 261
      non-neoplasm hospital outpatients, and 51 women recruited from the community. The
      daily sitting duration in both occupational- and leisure-time was measured using
      a validated questionnaire. The risks of ovarian cancer were assessed using
      multivariate logistic regression analysis accounting for demographic
      characteristics, body mass index, familial factors, hormonal status, family
      ovarian cancer history, physical activity (as weekly metabolic equivalent tasks),
      and total energy intake. RESULTS: Prolonged sitting duration was associated with
      an increase in ovarian cancer risk. The odds ratios were, respectively, 1.96 (95%
      confidence interval (CI): 1.2-3.2) with a significant trend (p = 0.007), 3.39
      (95% CI: 1.0-11.5), and 1.77 (95% CI: 1.0-3.1) for high level versus low level of
      sitting at work, sitting while watching television and total sitting duration.
      CONCLUSION: Sedentary behaviours were associated with an increase in epithelial
      ovarian cancer risk.

PMID- 14970739
TI  - Failure to detect prostate cancer in the PSA era: comments on N Engl J Med 2003;
      349: 215-224 and N Engl J Med 2003; 349: 335-342.

PMID- 14970741
TI  - Bone mineral density and markers of bone turnover in patients with glycogen
      storage disease types I, III and IX.
AB  - Patients with glycogen storage disease (GSD) types I, III and IX show reduced
      bone mineral content, but there is scarce data on new serum and urine markers of
      bone turnover or their relationship to bone densitometry. Six GSD I, four GSD III
      and four GSD IX patients underwent bone mineral density (BMD) measurement by dual
      energy X-ray absorptiometry. Free pyridinoline (fPYD):creatinine and free
      deoxypyridinoline (fDPD):creatinine ratios were analysed on random urines.
      Procollagen type I C-terminal propeptide, procollagen type I N-terminal
      propeptide (PINP), carboxyterminal telopeptide of type I collagen and bone
      specific alkaline phosphatase were analysed in serum. Some GSD I and GSD III
      patients had low or very low BMD. There was no difference in total body BMD z
      score between the GSD types after adjusting for height (p=0.110). Bone marker
      analysis showed no consistent pattern. Urine fPYD:creatinine ratio was raised in
      four GSD I and two GSD III patients, while serum PINP was inappropriately low in
      some of these patients. There was no clear correlation between any markers of
      bone destruction and total body z-score, but the patient with the lowest total
      body z-score showed the highest concentrations of both urinary fPYD:creatinine
      and fDPD:creatinine ratios. We conclude that some GSD I and GSD III patients have
      very low bone mineral density. There is no correlation between mineral density
      and bone markers in GSD patients. The inappropriately low concentration of PINP
      in association with the raised urinary fPYD:creatinine and fDPD:creatinine ratios
      seen in two GSD I patients reflect uncoupling of bone turnover. All these
      findings taken together suggest that some GSD I and GSD III patients may be at an
      increased risk of osteoporosis.

PMID- 14970742
TI  - Differential diagnosis of neonatal mild hypergalactosaemia detected by mass
      screening: clinical significance of portal vein imaging.
AB  - The aetiology of hypergalactosaemia in 100 neonates detected by screening using
      the Paigen method is discussed. Hypergalactosaemia was transient in 94 cases and
      persistent in 6. The aetiology among transient cases was unknown in 55, delayed
      closure of the ductus venosus in 19, heterozygous UDP-galactose 4-epimerase
      (GALE) deficiency in 16, and heterozygous galactose-1-phosphate uridyltransferase
      (GALT) deficiency in 6. The aetiology among persistent cases was hepatic
      haemangioendothelioma with portovenous shunting in 2, and patent ductus venosus
      with hypoplasia of the intrahepatic portal vein, citrin deficiency, homozygous
      GALE deficiency, and heterozygous GALE deficiency in one patient each. The
      abnormalities of the portal system were identified ultrasonographically at the
      initial consultation and measurements of the total bile acid and alpha
      fetoprotein concentrations were helpful in resolving the differential diagnosis.
      The causes of hypergalactosaemia varied, but a major cause was portosystemic
      shunt. Evaluation of patients with hypergalactosaemia should not be limited to
      enzymatic analysis, but should also include hepatic imaging, especially
      ultrasonography. Additionally, determination of total bile acids and alpha
      fetoprotein is helpful in identifying the aetiology of hypergalactosaemia in
      infants.

PMID- 14970743
TI  - Homozygous acute intermittent porphyria in a 7-year-old boy with massive
      excretions of porphyrins and porphyrin precursors.
AB  - A 7-year-old boy demonstrating hepatosplenomegaly, mild anaemia, mild mental
      retardation, yellow-brown teeth and dark red urine had excessively elevated
      levels of urinary delta-aminolevulinic acid, porphobilinogen and uroporphyrin.
      Furthermore hepta-, hexa-, penta- and copro(I)porphyrins were highly increased in
      urine. This pattern of porphyrin precursor and metabolite excretion is
      characteristic of acute intermittent porphyria. The decreased
      copro(III)/copro(I+III) ratio, normally not found in acute intermittent
      porphyria, is discussed. The porphobilinogen deaminase activity in red cells was
      decreased to 2-4%. Mutation analysis revealed a novel homozygous L81P mutation in
      exon 6 of the porphobilinogen deaminase gene. The father and mother, shown to be
      gene carriers of the same mutation, are asymptomatic and have normal urinary
      porphyrin precursor and metabolite excretion.

PMID- 14970744
TI  - A family showing recessively inherited multisystem pathology with aberrant
      splicing of the erythrocyte Band 7.2b ('stomatin') gene.
AB  - The case of a French child, born of consanguineous parents of Tunisian origin, is
      described. He showed a severe multisystem disease with dyserythropoietic,
      sideroblastic anaemia, delayed neurological development with hypotonia and
      convulsions, salt-losing nephropathy, chronic watery diarrhoea, lactic acidosis
      with mitochondrial dysfunction, brittle hair, hypergammaglobulinaemia, fatty
      liver with intermittent transaminasaemia, and terminal pulmonary fibrosis. Two
      siblings, of both sexes, were stillborn; two more lived only a short time. One
      sister is alive and well. SDS gel analysis of the red cell membranes showed a
      deficiency within 'Band 7' at 32 kDa. Analysis of the gene encoding 'stomatin',
      or 'erythrocyte membrane protein 7.2b', the principal protein of 'Band 7',
      revealed a complex series of aberrant spliceforms centred around exon 3, for
      which no explanatory genomic lesion could be found. The true underlying molecular
      cause of this condition remains obscure, but it suggests that the stomatin gene
      should be studied in other cases.

PMID- 14970745
TI  - Pearson syndrome and the role of deletion dimers and duplications in the mtDNA.
AB  - Pearson syndrome is an often fatal multisystem disease associated with
      mitochondrial DNA rearrangements. Here we report a patient with a novel mtDNA
      deletion of 3.4 kb ranging from nucleotides 6097 to 9541 in combination with
      deletion dimers. The mutation percentage in different tissues (blood, muscle and
      liver) varied between 64% and 95%. After a remission period of about a year, the
      patient suddenly died at the age of 3 years owing to a severe lactic acidosis. A
      second patient with a previously reported deletion of 8 kb and a milder phenotype
      was found to have mitochondrial duplications and died at the age of 10 years.
      From these data and data from previous reports, we hypothesize that duplications
      might be beneficial in the clinical course of the disease and in life expectancy.

PMID- 14970746
TI  - Diagnostic difficulties with common SURF1 mutations in patients with cytochrome
      oxidase-deficient Leigh syndrome.
AB  - In three unrelated patients with systemic cytochrome oxidase deficiency resulting
      from mutations in the SURF1 gene, the same mutation in the splice donor site of
      intron 3 was identified. All three patients were compound heterozygotes, two for
      the common insertion/deletion mutation in exon 4. In all three cases, complete
      definition of the causative mutations was only resolved by combined analysis of
      cDNA and genomic DNA. Several factors were identified that contributed to the
      diagnostic difficulties: preferential amplification of deleted cDNA, significant
      formation of heteroduplexes in cDNA PCR amplification and unequal representation
      of heterozygous peaks in genomic DNA sequences. These patients emphasize the need
      to perform mutation analysis on both cDNA and genomic DNA wherever possible.

PMID- 14970747
TI  - Reversion of hypertrophic cardiomyopathy in a patient with deficiency of the
      mitochondrial copper binding protein Sco2: is there a potential effect of copper?
AB  - Mutations in Sco2, a protein involved in copper trafficking to the terminal
      enzyme of the respiratory chain, cytochrome c oxidase, results in infantile
      hypertrophic cardioencephalomyopathy. We have recently shown that copper
      histidine (Cu-his) supplementation of Sco2-deficient myoblasts rescues COX
      activity in vitro. Here, we report a patient with SCO 2 mutations and with
      resolution of severe hypertrophic cardiomyopathy. Weighing up the evidence, the
      most likely explanation for the improved cardiac function in this patient was the
      subcutaneous application of Cu-his.

PMID- 14970748
TI  - Blood acylcarnitine levels in normal newborns and heterozygotes for medium-chain
      acyl-CoA dehydrogenase deficiency: a relationship between genotype and
      biochemical phenotype?
AB  - Patients with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency are unable to
      metabolize medium-chain fatty acids. Affected patients display a characteristic
      acylcarnitine profile when blood spots are collected after birth and analysed by
      tandem mass spectrometry. To determine the potential risk of metabolic
      decompensation in newborns with elevations of diagnostic metabolites
      (octanoylcarnitine>0.3, but <1 micromol/L), we investigated the relationship
      between octanoylcarnitine (C8) concentration in neonatal blood spots and the
      985A>G MCAD genotype. Octanoylcarnitine values from 7140 newborns' blood spots
      were sorted. The highest C8 was approximately 0.7 micromol/L, which is below the
      range in classical MCAD deficiency. Samples with C8 levels above 0.25 micromol/L
      (group C) represented 1.4% of the total. Values between 0.05 and 0.25 micromol/L
      (group B) made up 87.8% of the total; 10.8% of the samples had C8 values less
      than 0.05 micromol/L (group A). One hundred samples from each group were selected
      at random and genomic DNA was amplified by PCR and analysed for the presence of
      the 985A>G mutation. The analysed samples from groups A and B were all homozygous
      normal. The 100 samples from group C contained 26 samples that were heterozygous
      for the 985A>G mutation. These findings indicated that the frequency distribution
      of heterozygotes is not random within this population. Group C was further
      divided into C1, the 26 heterozygotes, and C2, the remaining 74 newborns in group
      C. In group C1 only 2 (8%) were in the 'high-risk' group characterized by either
      low birth weight or requiring admission to the neonatal intensive care unit. In
      contrast, 28 (38%) from C2 had low birth weight or were in the neonatal intensive
      care unit. In our dataset, C8/C2 and C8/C12 ratios were also significantly
      elevated in both groups C1 and C2 compared to controls (group B). In contrast to
      what others have reported, the ratio of C8/C10 did not differentiate the group B
      controls from heterozygotes or other patients in metabolic distress (group C2),
      but were lower than those seen in classic MCAD or mild MCAD deficiency.

PMID- 14970749
TI  - The distribution of white blood cell fat oxidation in health and disease.
AB  - Fat oxidation is important for maintaining health and for supplying energy for
      exercise. We have proposed that the predisposition for individual rates of fat
      oxidation is determined genetically but may be modulated by acute exercise or
      exercise training. The purpose of this study was to examine cellular fat
      oxidation in white blood cells (WBC) using [9,10-3H]palmitic acid. Sedentary
      controls free of symptoms (SED-C, n=32), were compared with known carnitine
      palmitoyltransferase (CPT) II-deficient patients (n =2), patients with fatiguing
      diseases (chronic fatigue syndrome, CFS, n=6; multiple sclerosis, MS, n=31),
      obesity (OB, n=5), eating disorders (ED, n=16), sedentary individuals prior to
      and after exercise (SED-Ex, n=12), exercise-trained sedentary individuals (SED
      Tr, n=12), and elite runners (ER, n=5). Fat oxidation in WBC for all subjects was
      normally distributed (mean=0.270 +/- 0.090 nmol/h per 10(9) WBC) and ranged from
      0.09 nmol/h per 10(9) WBC in CPT II-deficient patients to 0.59 nmol/h per 10(9)
      WBC in ER. There were no significant sex or acute exercise effects on WBC fat
      oxidation. Patients with MS, OB or ED were not different from SED-C; however, in
      CPT II-deficient patients, fat oxidation was low, while that of CFS patients was
      high. Exercise training in SED-C resulted in a 16% increase in fat oxidation but
      in ER it was still 97% higher than in SED-C. We propose that while WBC fat
      oxidation is not significantly affected by sex or acute exercise, and only by 15
      20% with training, genetic factors play a role in determining both high and low
      fat oxidation in certain groups of individuals. The genetic predisposition for
      individual rates of fat oxidation may be easily measured using WBC fat oxidation,
      as has been shown for CPT II-deficient patients and for elite runners. Ranges of
      WBC fat oxidation that are abnormally low (<20 nmol/h per 10(9) WBC, normal 20
      35) or high (>35 nmol/h per 10(9) WBC) are proposed based on genetic factors
      evaluated in this study.

PMID- 14970750
TI  - Radiofrequency incision and lay open technique of pilonidal sinus (clinical
      practice paper on modified technique).
AB  - With the uncertainty as to the etiology and the complexities often encountered in
      its treatment, a pilonidal sinus has been considered as a tricky disease. Wide
      varieties of approaches are employed in dealing with this ailment ranging from a
      conservative treatment to an extensive surgical excision or repair. However, a
      method of simple lying open of pilonidal sinus is still considered as the favored
      one. We describe a modified approach to the procedure of incision and lying open
      the sinus tracts. This retrospective study describes 18 patients of chronic
      pilonidal sinus treated with a technique of radiofrequency surgery under local
      anesthesia. There were 12 males and 6 females within an age group ranging from 16
      to 30. The patients were subjected to a follow-up for a period of 18 months. The
      patients were discharged on the same day of the procedure. Mean period off work
      was 7 days. The average healing time recorded was 67 days. Two wound
      complications in the form of premature closure of the skin edges were noted,
      requiring trimming of the edges. One of these two remained unhealed. At the last
      follow-up, no recurrence was found in the remaining 17 patients. In the era when
      the emphasis is on the criteria like minimum hospital stay, less postoperative
      pain, early resumption to work and a reduced recurrence rate, there is a future
      to the procedure of incision and lying open of the pilonidal sinuses by using the
      radiofrequency wave.

PMID- 14970751
TI  - Selective brain hypothermia protects against hypoxic-ischemic injury in newborn
      rats by reducing hydroxyl radical production.
AB  - We hypothesized that selective brain hypothermia (SBHT) decreases production of
      hydroxyl radicals (*OH) induced by hypoxia-ischemia (H-I) and reperfusion and
      attenuates neuronal damage in neonatal rat brain. Anesthetized 7-day-old rats
      were divided into a normothermia (NT) group (n=6) and a SBHT group (n=7) and
      subjected to 90-min H-I, followed by a 90-min recovery period. Brain temperature
      (BT) was regulated by a water-cooled metallic plate placed under the head. The BT
      of the SBHT group was set at 31.0+/-1.0 degrees C during the H-I and recovery
      period. Microdialysis and the salicylate-trapping method were used to detect *OH
      in the striatum. Neuronal damage was quantified by counting the surviving neurons
      at 120 hr after reperfusion. The NT group had significant increases in 2,3
      dihydroxybenzoic acid (DHBA) (223+/-166%) and 2,5-DHBA (321+/-153%) above
      baseline levels. The increases in 2,3-DHBA (127+/-40%) and 2,5-DHBA (133+/-33%)
      were significantly lower (p < 0.01) in the SBHT group. The number of surviving
      neurons was decreased significantly in the NT group but not in the SBHT group. We
      conclude that SBHT reduces *OH production during H-I and reperfusion and has
      protective effects against neuronal damage.

PMID- 14970752
TI  - Alpha E- and alpha N-catenin expression in dorsal root ganglia and spinal cord.
AB  - The localization of alpha E- and alpha N-catenin in dorsal root ganglia and
      spinal cord was examined immunocytochemically. Alpha E- and alpha N-catenin
      appeared to be co-localized in cell bodies of neurons in dorsal root ganglia, but
      alpha N-catenin was not expressed in cell bodies of neurons in the ventral horn
      that showed alpha E-catenin expression. These findings indicate the possibility
      that the type of alpha catenin expressed in neurons differs with its functional
      property (e.g. sensory or motor).

PMID- 14970754
TI  - Evaluation of photoelastic stress patterns produced by various designs of
      bilateral distal-extension removable partial dentures. 1997.

PMID- 14970755
TI  - Immediate loading of implants in edentulous mandible maintaining vertical
      dimension: A clinical report.
AB  - Clinical treatments that provide immediate prostheses after implant placement
      pose a challenge to prosthodontists. This clinical report describes retaining 1
      tooth for maintaining the vertical dimension of occlusion in the process of
      immediate loading of implants in the edentulous mandible. This process assisted
      in the patient's adaptation to the interim removable partial denture and ensured
      the maintenance of the vertical dimension of occlusion during all aspects of
      therapy.

PMID- 14970756
TI  - Connective tissue graft to correct peri-implant soft tissue margin: A clinical
      report.
AB  - This clinical report describes the use of a subepithelial connective tissue graft
      to recontour a soft tissue margin discrepancy for a single-implant crown in the
      anterior maxilla. This procedure demonstrates that the use of soft tissue grafts
      to correct an esthetic deficiency may be a feasible approach to establish new and
      stable peri-implant soft tissue contours. The patient presented was followed for
      18 months.

PMID- 14970757
TI  - Nasal stent fabrication involved in nasal reconstruction: Clinical report of two
      patient treatments.
AB  - Total or near-total rhinectomy during tumor ablative surgery creates a large
      postsurgical defect. Surgical or prosthetic reconstruction may be considered.
      Surgical reconstruction of such a defect depends on support of the reconstructive
      tissues to prevent collapse. Without support, the esthetic results and airway
      patency are compromised. The purpose of this clinical report is to present the
      use of a nasal stent to support soft and hard tissues for the reconstruction of
      near-total rhinectomy in 2 patients.

PMID- 14970758
TI  - Influence of powder/liquid mixing ratio on porosity and translucency of dental
      porcelains.
AB  - STATEMENT OF PROBLEM: Dental technicians use a variety of techniques when
      condensing dental porcelains. It is unclear whether these techniques affect the
      total porosity and translucency of dental porcelains. PURPOSE: The objective of
      this study was to determine whether varying the powder/liquid ratio during
      condensation affects porosity and translucency of porcelains. Material and
      methods Duceram LFC dentin, Duceram LFC incisal, IPS Eris dentin, and IPS Eris
      incisal porcelains were studied. For each specimen, 1.0 g of porcelain powder was
      mixed with 1 of 3 different volumes of deionized water to form a slurry with a
      thin, medium, or thick consistency. The slurries were condensed in a plastic
      syringe mold, fired, and polished to a 3-microm finish to form 12 groups of 4
      specimens each (14-mm diameter, 1.10-mm thickness). The apparent density (g/mL)
      of each specimen was measured using Archimedes method, and the porosity (%)
      calculated. Each specimen was coupled to standard ceramic tiles using an
      immersion liquid, and the color shade was measured in CIE Yxy coordinates using a
      tristimulus colorimeter. Translucency was assessed by calculating the contrast
      ratio of shade value (Y) in front of black versus white backgrounds. Two-way
      analysis of variance and Tukey's multiple comparison tests (alpha = .05) were
      used to test for significant effects of factors. RESULTS: Porcelain type and
      powder/liquid ratio had a significant interactive effect on the apparent density
      (P < .001) and on total porosity (P = .003); however, there was no consistent
      trend. The powder/liquid ratio did not significantly affect translucency (P =
      .28), but porcelain type had a significant effect on translucency (P < .001).
      CONCLUSION: In this in vitro study, total porosity of specimens prepared using 4
      porcelains was found to be sensitive to powder/liquid ratio; whereas translucency
      was found to be insensitive to powder/liquid ratio.

PMID- 14970759
TI  - Glass/ceramic/refractory techniques, their development and introduction into
      dentistry: A historical literature review.
AB  - This review considered the development of glass, ceramic, refractory materials,
      and techniques over a period of 25,000 years, from the time of stone-age man to
      their introduction into dentistry. Currently a wide variety of all-ceramic dental
      restorations are provided using alumina-reinforced, leucite-forming, and novel
      glass and ceramic materials along with a range of refractory materials and
      associated techniques. However, some of the problems of dimensional and thermal
      change experienced by early craftsmen still persist during current laboratory
      fabrication techniques. Early English archaeological and dental publications were
      obtained through the Archaeology Education Department of the British Museum in
      London and the Archives of the British Dental Association Library. More recent
      peer-reviewed articles published from 1966 to the present were obtained through
      MEDLINE.

PMID- 14970760
TI  - The influence of occlusal loading location on stresses transferred to implant
      supported prostheses and supporting bone: A three-dimensional finite element
      study.
AB  - STATEMENT OF PROBLEM: Information about the influence of occlusal loading by
      location on the stress distribution in an implant-supported fixed partial denture
      and supporting bone tissue is limited. PURPOSE: The purpose of this study was to
      investigate the effect of loading at 1 to 3 different locations on the occlusal
      surface of a tooth on the stress distributions in an implant-supported mandibular
      fixed partial denture (FPD) and surrounding bone, using 3-dimensional finite
      element analysis. MATERIAL AND METHODS: A 3-dimensional finite element model of a
      mandibular section of bone (Type 2) with missing second premolar and its
      superstructures were used in this study. A 1-piece 4.1 x 10-mm screw-shape ITI
      dental implant system (solid implant) was modeled for this study. Cobalt-Chromium
      (Wiron 99) was used as the crown framework material and porcelain was used for
      occlusal surface. The implant and its superstructure were simulated in a
      Pro/Engineer 2000i program. Total loads at 300 N were applied at the following
      locations: 1) tip of buccal cusp (300 N); 2) tip of buccal cusp (150 N) and
      distal fossa (150 N); or 3) tip of buccal cusp (100 N), distal fossa (100 N), and
      mesial fossa (100 N). RESULTS: The results demonstrated that vertical loading at
      1 location resulted in high stress values within the bone and implant. Close
      stress levels were observed within the bone for loading at 2 locations and 3
      locations; the former created the most extreme stresses and the latter the most
      even stresses within the bone. With loading at 2 or 3 locations, stresses were
      concentrated on the framework and occlusal surface of the FPD, and low stresses
      were distributed to the bone. CONCLUSION: For the loading conditions
      investigated, the optimal combination of vertical loading was found to be loading
      at 2 or 3 locations which decreased the stresses within the bone. In this
      situation, von Mises stresses were concentrated on the framework and occlusal
      surface of the FPD.

PMID- 14970761
TI  - The efficiency of different light sources to polymerize composite beneath a
      simulated ceramic restoration.
AB  - STATEMENT OF PROBLEM: Inadequate polymerization diminishes the physical
      properties of composite and compromises material strength. Newly developed light
      polymerizing units (plasma arc and high intensity halogen) operate at relatively
      high intensity and are purported to provide optimum properties to composites in a
      shorter time. PURPOSE: The aim of this in vitro study was to examine the
      polymerization efficacy of 3 different polymerization units through a simulated
      ceramic restoration by determining degree of monomer conversion of a composite
      luting Material. MATERIAL AND METHODS: A conventional halogen light, a plasma arc
      light, and a high-intensity halogen light were used to polymerize a composite
      (Variolink II) with or without catalyst. A pressable ceramic block (5 mm in
      diameter, 2 mm in height) was used as an interface between the polymerizing light
      tip and composite. The composite/veneer combination was exposed to 2 different
      polymerization time protocols for each polymerization unit: (1) 20 or 40 seconds
      for conventional halogen light, (2) 3 or 6 seconds for plasma arc light, and (3)
      10 or 20 seconds (under ramp mode) for the high-intensity halogen light. Using
      different light units, 120 composite specimens were evaluated (n = 5). Fourier
      transformation infrared spectroscopy was used to determine the level of light
      polymerization of the resin through the ceramic material with each of the light
      sources immediately after polymerization or after 24 hours. Degree of conversion
      was calculated as a percentage of experimentally polymerized versus maximally
      polymerized composite. The data were analyzed by 4-factor analysis of variance
      (alpha = .05). Independent t tests (alpha = .05) were used to detect differences
      between groups defined by the specific interacting variables. RESULTS: Degree of
      conversion values varied with the light source (P < .05), polymerization type (P
      < .05), testing time (P < .01), and exposure to each light source (P < .01).
      Significant interactions were present between light source and polymerization
      type (P = .00), light source and testing time (P = .007), and polymerization type
      and testing time (P = .004). The degree of conversion values were significantly
      higher in dual-polymerized specimens after 24 hours (P < .01), but there were no
      significant differences in light-polymerized specimens after 24 hours. The degree
      of conversion values achieved were significantly lower (P < .05) when specimens
      were dual polymerized by conventional halogen light and measured immediately
      (31.59 +/- 7.76). The degree of conversion values achieved were significantly (P
      < .05) higher with dual polymerization by high-intensity halogen measured after
      24 hours (65.06 +/- 8.14). There were no other significant differences among
      groups. CONCLUSION: The highest degree of conversion values of composite were
      achieved with polymerization by high-intensity halogen. The plasma arc light
      achieved similar polymerization of composite through ceramic material in a
      markedly shorter period than conventional halogen light.

PMID- 14970762
TI  - Fatigue resistance and stiffness of glass fiber-reinforced urethane
      dimethacrylate composite.
AB  - STATEMENT OF PROBLEM: Retentive properties of cast metal clasps decrease over
      time because of metal fatigue. Novel fiber-reinforced composite materials are
      purported to have increased fatigue resistance compared with metals and may offer
      a solution to the problem of metal fatigue. PURPOSE: The aim of this study was to
      investigate the fatigue resistance and stiffness of E-glass fiber-reinforced
      composite. MATERIAL AND METHODS: Twelve cylindrical fiber-reinforced composite
      test cylinders (2 mm in diameter and 60 mm in length) were made from light
      polymerized urethane dimethacrylate monomer with unidirectional, single-stranded,
      polymer preimpregnated E-glass fiber reinforcement. Six cylinders were stored in
      dry conditions and 6 in distilled water for 30 days before testing. Fatigue
      resistance was measured by a constant-deflection fatigue test with 1 mm of
      deflection across a specimen span of 11 mm for a maximum of 150,000 loading
      cycles. The resistance of the cylinder against deflection was measured (N) and
      the mean values of the force were compared by 1-way analysis of variance (alpha =
      .05). The flexural modulus (GPa) was calculated for the dry and water-stored
      cylinders for the first loading cycle. Scanning electron microscopy was used to
      assess the distribution of the fibers, and the volume percent of fibers and
      polymer were assessed by combustion analysis. RESULTS: The test cylinders did not
      fracture due to fatigue following 150,000 loading cycles. Flexural modulus at the
      first loading cycle was 18.9 (+/- 2.9) GPa and 17.5 (+/- 1.7) GPa for the dry and
      water-stored cylinders, respectively. The mean force required to cause the first
      1-mm deflection was 33.5 (+/- 5.2) N and 37.7 (+/- 3.6) N for the dry and water
      stored cylinders, respectively; however, the differences were not significant.
      After 150,000 cycles the mean force to cause 1-mm deflection was significantly
      reduced to 23.4 (+/- 8.5) N and 13.1 (+/- 3.5) N, respectively (P < .0001).
      Scanning electron microscopy highlighted fiber- and polymer-rich areas within the
      specimens and indicated that individual fibers were well impregnated with resin.
      The combustion analysis studies identified the fiber content to be 35.9 vol%.
      CONCLUSION: The results of this study suggest that the fatigue resistance of the
      fiber-reinforced material examined was increased; however, the reduction in
      flexural modulus of fiber-reinforced composites may restrict their use where high
      rigidity is required, such as in removable partial denture clasps.

PMID- 14970763
TI  - In vitro evaluation of the influence of repairing condition of denture base resin
      on the bonding of autopolymerizing resins.
AB  - STATEMENT OF PROBLEM: Bonding failures of repair resin to denture base resin
      occurs when denture base resin is wet, however, little is known of how water
      relates to failures. PURPOSE: This study evaluated the influence of water
      absorbed in denture base resin on the bond strength and resistance to cyclic
      thermal stresses of autopolymerizing resins bonded to denture base resin.
      MATERIAL AND METHODS: Denture base resin disks (n = 180; 12 mm diameter and 3 mm
      thick) were fabricated from heat-polymerized acrylic resin (Lucitone 199). The
      disks were divided into groups (n = 60) with 3 conditions of water content: (1)
      complete water saturation (control), (2) superficial desiccation by blowing air
      on the specimen, or (3) complete desiccation. Each denture base specimen received
      1 of 3 surface treatments (n = 20) including: (1) no treatment, (2) airborne
      particle abrasion, or (3) methylene chloride application. An autopolymerizing
      repair resin (Repair Material, n = 10) or reline resin (Tokuso Rebase Normal set,
      n = 10) was applied to the bonding area (5 mm diameter) and polymerized at 37
      degrees C for 10 minutes. The resistance to cyclic thermal stress was determined
      after subjecting the specimens to 50,000 thermal cycles between 4 degrees C and
      60 degrees C water baths with a 1-minute dwell time (n = 5 per group). Bond
      strength (MPa) was measured by shear bond testing at a 1.0 mm/min crosshead speed
      until the applied resin debonded from denture base resin. Data were statistically
      analyzed by 3-way analysis of variance and multiple comparisons among the groups
      were performed with Bonferroni test (alpha = .05). RESULTS: The mean bond
      strengths of repair resin to airborne-particle-abraded denture base specimens
      were not significantly influenced by either thermal cycling or water content. The
      mean bond strengths of reline resin significantly decreased after thermal cycling
      (P < .0001) regardless of the conditions of surface treatment and water content.
      For methylene chloride treated specimens, bond strengths of both repair and
      reline resins to completely water saturated specimens were significantly higher
      than those of completely desiccated specimens (P = .0048 for repair resin, P <
      .0001 for reline resin) after thermal cycling. CONCLUSIONS: Bond strengths of
      autopolymerizing resin to denture base resin were not significantly influenced by
      water content of denture base resin but were significantly influenced by resin
      type, thermal cycling, and surface treatment.

PMID- 14970764
TI  - The effect of clenching on condylar position: A vector analysis model.
AB  - STATEMENT OF THE PROBLEM: Clinicians often disagree about the acceptable position
      of the condyle in the articular fossa. Agreement as to what position the condyle
      disk assembly assumes on the articular eminence while subjected to the forces of
      the elevator muscles of the mandible is important. PURPOSE: This simulation study
      investigated the position of the condyle-disk assembly on the articular eminence
      while subjected to the forces of the elevator muscles of the mandible during
      clenching. MATERIAL AND METHODS: Using the 2 conditions of static equilibrium, a
      vector analysis of a 2-dimensional model of the temporomandibular joint was
      developed. The dynamics of the condyle-disk assembly during muscle loading were
      analyzed. The vector sum of the masticatory muscle forces was determined by
      assuming that the maximum force developed by each contributing muscle was
      proportional with the physiologic cross section of the muscle. The effect of the
      resultant force vector of the combined muscle action applied to the condyle was
      analyzed for the orthogonal and acute angle situations. RESULTS: When the vector
      sum was orthogonal on the eminence, the condyle was in stable equilibrium. The
      stable equilibrium was found in the anterior-superior position in the fossa. When
      the vector sum was at an acute angle to the eminence, the condyle was subject to
      a translation force that displaced it into the anterior-superior equilibrium
      position. CONCLUSION: Within the limitation of this study, vector analysis
      suggested that the anterior-superior position of the condyle-disk assembly on the
      eminence was the most stable equilibrium position. All other tested positions of
      the condyle were less stable and maintained at the expense of other structures.

PMID- 14970765
TI  - A multicenter clinical trial on the use of pulsed electromagnetic fields in the
      treatment of temporomandibular disorders.
AB  - STATEMENT OF THE PROBLEM: Pulsed electromagnetic fields have shown therapeutic
      benefit in the treatment of numerous forms of osteoarthritis but have not been
      evaluated for their effects on the temporomandibular joint (TMJ). PURPOSE: The
      aim of this study was to examine the effects of pulsed electromagnetic fields in
      the treatment of patients with temporomandibular disorders (TMD). MATERIALS AND
      METHODS: A multicenter clinical trial compared active treatment of 36 patients
      using pulsed electromagnetic fields to placebo treatment of 42 patients with TMD
      with pain in 1 or both TMJs and/or limited opening of less than 40 mm. Subjective
      parameters including pain intensity, pain frequency, degree of limitation,
      restriction of daily life, and intensity and frequency of joint noises were
      evaluated using a visual analog scale. Trained, blinded examiners assessed the
      clinical parameters according to Research Diagnostic Criteria for
      temporomandibular disorders before treatment (baseline), directly after nine 1
      hour treatments on consecutive working days, 6 weeks after treatment, and 4
      months after treatment. Statistical evaluation was done using the Friedman test,
      and by paired comparison between baseline and follow-up examinations using the U
      test (P < .05). RESULTS: Seventy-six patients completed the study. For both the
      active and placebo treatment, significant improvements were seen in the
      subjective data (P < .01). Patients with anterior disk displacement without
      reduction also showed significant improvements in active mouth opening (P =
      .015), patients with ostheoarthritis only showed improvements in some of the
      subjective parameters (P < .03), and patients with anterior disk displacement
      with reduction showed no improvement at all. CONCLUSIONS: Pulsed electromagnetic
      fields had no specific treatment effects in patients with temporomandibular
      disorders.

PMID- 14970766
TI  - Minimizing movement of an orbital prosthesis retained by an obturator prosthesis.
AB  - This article describes a procedure in which an obturator with an integrated
      spring-loaded rewinding device retains an orbital prosthesis. This system
      minimizes movement of the orbital prosthesis during mastication and thus prevents
      adhesive failure.

PMID- 14970767
TI  - Fiber-reinforced post and core adapted to a previous metal ceramic crown.
AB  - A technique to create a fiber-reinforced anatomic post and core adapted to an
      existing crown is described. This technique is performed with a quartz post
      adapted to root canal anatomy, using a core composite material. With this
      technique, a well-adapted anatomic post and core may be achieved in a clinical
      session.

PMID- 14970768
TI  - O-ring attachments for transitional implant-retained overdentures.
AB  - The lack of proper stability and retention is frequently found in mandibular
      complete dentures. The stability and retention of existing complete dentures may
      be improved by using transitional implants (TIs) incorporating the O-ring
      retention system. This article describes the procedures used to convert an
      existing conventional complete denture to a TI-retained complete overdenture with
      O-ring.

PMID- 14970769
TI  - A method for seating an implant-supported fixed prosthesis on ITI solid
      abutments.

PMID- 14970770
TI  - A simple method for cleaning zinc oxide-eugenol provisional cement residues from
      the intaglio surface of casting restorations.

PMID- 14970772
TI  - COX-2 selective inhibitors: a literature review of analgesic efficacy and safety
      in oral-maxillofacial surgery.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly
      prescribed analgesic agents in surgical outpatients. Major limitations of NSAIDs
      are their gastrointestinal (GI) adverse events (perforation, ulceration, and
      bleeding), impairment of hemostatic function, and renal failure (with long-term
      therapy). A new class of NSAIDs, the COX-2 selective inhibitors (CSIs or Coxibs),
      have been developed with the aim of reducing the GI adverse events of traditional
      NSAIDs while maintaining their effective anti-inflammatory and analgesic
      properties. OBJECTIVE: This is a narrative review of the literature aimed to
      discuss analgesic efficacy, clinical safety and cost-benefit ratio of CSIs in the
      treatment of post-oral surgery pain. METHODS: Relevant drug and clinical studies
      of analgesic efficacy and safety of CSIs in the management of postoperative
      dental pain were identified through searches of MEDLINE/PubMed, in peer-reviewed
      journals of medicine and dentistry. The Food and Drug Administration Web site was
      searched for data of tolerability. Hand-searching included several dental
      journals and bibliographies of relevant studies. The last electronic search was
      conducted in April 2003. RESULTS: Data from well-designed, randomized, controlled
      trials of CSIs on the management of post-oral surgery pain indicate that these
      drugs are as well-effective analgesic agents as traditional NSAIDs and offer
      clinical advantages in terms of GI safety and unimpaired platelet function. CSIs
      do not offer advantages of renal safety over traditional NSAIDs. CONCLUSION:
      Although CSIs display analgesic efficacy similar to that of traditional NSAIDs in
      the treatment of acute, post-oral surgery pain, there is reasonable evidence that
      these new drugs are preferable in patients who are at an increased risk of
      developing serious upper-GI complications, in patients who take aspirin for
      cardiovascular comorbid conditions, and in those allergic to aspirin.
      Furthermore, CSIs may be given more safely than NSAIDs in perioperative settings,
      because of their lack of impairment of the blood-clotting. However, the high
      costs of CSIs available at present limit their routine use in the short period of
      postoperative dental pain-in most cases 2 to 4 days after surgery-because there
      is not an increased risk of developing serious GI complications with the use of
      cost-saving NSAIDs. The GI safety advantages of CSIs may improve the tolerability
      of long-duration analgesic therapies, such as cases of painful temporomandibular
      joint disorders and chronic orofacial pain. Further studies are needed to
      determine the cost-benefit ratio of using CSIs for the management of acute pain.

PMID- 14970773
TI  - Immediate reconstruction of maxilla with bone grafts supported by pedicled buccal
      fat pad graft.
AB  - PURPOSE: To reconstruct immediately the maxilla with bone grafts after partial
      maxillary resection and solve complications of exposed bone grafts to the
      maxillary sinus leading to a high rate of bone infection and sequestration. STUDY
      DESIGN: Thirty-eight patients were treated by immediate reconstruction of the
      maxilla with bone grafts supported by pedicled buccal fat pad (BFP) graft. The
      facial contour, the bone healing of the bone grafts, and the function of the
      maxillary sinus were evaluated with the Waters radiograph and speech evaluation.
      RESULTS: The postoperative healing was satisfactory with normal mouth opening and
      symmetrical contour of the face. The function of the maxillary sinus was restored
      with satisfactory speech and symmetrical density on radiograph and the healing of
      the bone grafts was good without complications such as bone resorption and
      sequestration. CONCLUSIONS: Immediate reconstruction of the maxilla with bone
      grafts supported by pedicled BFP grafts can restore the facial contour and the
      function of the maxillary sinus for the patients with partial maxillary
      resection. It provides a good method to reconstruct the maxillary defects and
      function in the mouth.

PMID- 14970774
TI  - Evaluation of a poly-l-lactic acid membrane and membrane fixing pin for guided
      tissue regeneration on bone defects in dogs.
AB  - OBJECTIVES: The purpose of the study was to clarify the usefulness of a poly-l
      lactic acid and membrane fixing pin, used in combination with guided bone
      regeneration, on bone defects in dogs. STUDY DESIGN: Osteotomies bone defects
      were created in 8 beagle dogs. Group I: one defect was covered with test membrane
      and held by fixing pins. Group II: the other defect was covered test membrane and
      not held by fixing pins. The control group received no membrane. The dogs were
      killed after 24 or 36 weeks of healing. Sections were stained and evaluated
      microscopically. Data were analyzed statistically. RESULTS: The degradation and
      resorption of test membrane was not observed at 24 weeks but was noted at 36
      weeks. After 24 and 36 weeks, most of Group I defects were completely closed with
      new bone, while in the control defects, only a small amount of new bone was
      observed at the bottom of the bone defects. After 36 weeks, the percentage of new
      bone volume (62.2%) in the space beneath the test membrane and membrane fixing
      pin (Group I) was greater than that without a membrane fixing pin-53.2% (Group
      II), whereas only 43.9% of the defect area in the control group was filled with
      new bone. CONCLUSION: The results of this study show that a poly-l-lactic acid
      membrane and membrane fixing pin permit bone regeneration that can be ensured by
      excluding surrounding soft tissues from the wound area.

PMID- 14970775
TI  - Injection pain and postinjection pain of the palatal-anterior superior alveolar
      injection, administered with the Wand Plus system, comparing 2% lidocaine with
      1:100,000 epinephrine to 3% mepivacaine.
AB  - PURPOSE: The purpose of this prospective, randomized, double-blind study was to
      compare injection pain and postinjection pain of 2% lidocaine with 1:100,000
      epinephrine and 3% mepivacaine using the computer-assisted Wand Plus injection
      system to administer the palatal-anterior superior alveolar (P-ASA) injection.
      Additionally study was done to determine if the use of topical anesthetic
      decreased the pain of needle insertion with the P-ASA injection. STUDY DESIGN:
      Using a crossover design, 40 subjects randomly received, in a double-blind
      manner, P-ASA injections of 1.4 mL of 2% lidocaine with 1:100,000 epinephrine and
      1.4 mL of 3% mepivacaine, at 2 separate appointments. The P-ASA injection was
      administered, utilizing the Wand Plus system, 6 to 10 mm into the incisive canal
      located lingual to the central incisors. The pain of needle insertion, needle
      placement, solution deposition and postinjection pain were recorded on a Heft
      Parker visual analog scale for the 2 P-ASA injections. Eighty injections were
      randomly administered in the study, 40 using topical anesthetic gel and 40 using
      a placebo gel. RESULTS: For needle insertion, 30% of the subjects reported
      moderate/severe pain with the lidocaine solution and 43% reported moderate/severe
      pain with the mepivacaine solution. There was no significant difference (P > .05)
      between the topical and placebo groups. For needle placement into the incisive
      canal, 54% of the subjects reported moderate/severe pain with the lidocaine
      solution and 58% reported moderate/severe pain with the mepivacaine solution. For
      anesthetic solution deposition, 8% of the subjects reported moderate pain with
      the lidocaine solution and 12% reported moderate pain with the mepivacaine
      solution. There were no significant differences (P > .05) between the lidocaine
      and mepivacaine solutions. Regarding postinjection pain, when anesthesia wore off
      on the day of the injection, 20% of the subjects reported moderate/severe pain
      with the lidocaine solution and 14% reported moderate/severe pain with the
      mepivacaine solution. Pain ratings decreased over the next 3 days. There were no
      significant differences (P > .05) between the lidocaine and mepivacaine
      solutions. Postinjection, 12% and 18% of the subjects experienced temporary
      numbness/paresthesia of the incisive papilla with the lidocaine and mepivacaine
      solutions, respectively. Twenty percent and 28% of the subjects had incisive
      papilla swelling or soreness with the lidocaine and mepivacaine solutions,
      respectively. There were no significant differences (P > .05) between the
      lidocaine and mepivacaine solutions. CONCLUSIONS: The P-ASA injection of 1.4 mL
      of 2% lidocaine with 1:100,000 epinephrine or 3% mepivacaine, administered with
      the Wand Plus, has the potential to be a painful injection. The use of topical
      anesthetic did not significantly reduce pain of needle insertion when compared to
      a placebo. The incidence of postinjection pain, temporary numbness/paresthesia,
      and incisive papilla swelling or soreness would indicate that some pain and
      problems occur with the P-ASA technique, regardless of whether 2% lidocaine with
      1:100,000 epinephrine or 3% mepivacaine is used.

PMID- 14970776
TI  - A prospective study of salivary gland function in patients undergoing
      radiotherapy for squamous cell carcinoma of the oropharynx.
AB  - OBJECTIVE: We sought to investigate the impact of head and neck cancer treatment
      on salivary function. STUDY DESIGN: The study was conducted on 54 patients with
      advanced squamous cell carcinoma with confirmed (n = 50) or suspected (n = 4)
      primary oropharyngeal localization who were treated with radiation alone or in
      combination with surgery or chemotherapy, or both. The following groups were
      considered in the evaluation: 1, the entire pool of patients; 2, those undergoing
      surgery and those not undergoing surgery before radiation; 3, those undergoing
      resection and those not undergoing resection of the submandibular gland. The flow
      rates, pH, and buffering capacity were determined before, during, and up to 12
      months after the completion of radiation. RESULTS: Head and neck surgery,
      particularly when submandibular gland resection was performed, had a negative
      impact on salivary flow rates but did not influence pH or buffering capacity.
      Nonetheless, the effect of surgery on salivary flow rates decreased progressively
      and disappeared at 3 to 6 months after radiotherapy. More than two thirds of the
      salivary output was lost during radiation treatment. All patients were
      experiencing salivary dysfunction at 1 year after completion of radiotherapy,
      with average decreases of 93% (P < .0001) and 95% (P < .0001) for whole resting
      salivary flow and whole stimulated salivary flow, respectively, compared with the
      preradiotherapy values. The buffering capacity decreased to 67% of its
      preradiotherapy value, and whole stimulated saliva became acidic. CONCLUSIONS:
      The result of this study confirms that cancer treatment involving full-dose
      radiotherapy (RTH) to all major salivary glands for locally advanced squamous
      cell carcinoma of the oropharynx induces severe hyposalivation with alteration of
      salivary pH and buffering capacity. Head and neck surgery has a negative impact
      on salivary flow rates, especially when the submandibular gland is removed.
      However, surgery before irradiation is not a factor aggravating hyposalivation
      when postoperative radiotherapy includes all the major salivary glands.

PMID- 14970777
TI  - The efficacy of pilocarpine and bethanechol upon saliva production in cancer
      patients with hyposalivation following radiation therapy.
AB  - PURPOSE: Pilocarpine and bethanechol have been reported as potentially effective
      sialogogues for xerostomic patients. The purpose of the present study was to
      compare the efficacy of bethanechol to that of pilocarpine in patients with dry
      mouth following cancer therapy. STUDY DESIGN: Patients with documented
      hyposalivation were provided pilocarpine or bethanechol for 2-3 weeks in an open
      label randomized crossover study. Baseline and weekly whole resting saliva (WRS)
      and whole stimulated saliva (WSS) were obtained for 5 minutes. Subjective
      response and side effects were recorded. RESULTS: Forty-two xerostomic patients
      who had received radiation therapy to the head and neck participated. The
      increase in the WRS and WSS with each medication independently was limited.
      Statistically significant increase in WRS was seen for both medications when all
      patients using either agent were analyzed, but no statistically significant
      increase in WSS was found.Twenty-seven patients completed the crossover protocol.
      No significant difference in the effect was noted between each of the 2 drugs
      whether they were prescribed as the first or second drug in the crossover.
      Statistically significant improvement in subjective report of saliva
      production/mouth wetness was seen for patients on either medication. This study
      suggests that subjective improvement in symptoms of dry mouth may be related to
      resting saliva production, and not to stimulated saliva production. No
      statistically significant differences in adverse side effects were reported
      between the medications prescribed. The most common side effects were minor and
      included frequent urination, dizziness, and increased sweating. CONCLUSIONS: The
      findings indicate that head and neck radiation-treated patients with established
      hyposalivation will respond minimally to systemic sialagogues and while they may
      experience an increase in resting saliva little change in stimulated saliva may
      occur. It is not known whether relatively small increases in saliva are
      beneficial in maintaining oral health; however, subjective improvement suggests
      improved quality of life. While it is not known if prolonged use of a sialagogue
      will have increased effects, the limited increase in saliva seen following the
      second drug of the crossover suggests that prolonged use of a sialagogue may
      further increase saliva production.

PMID- 14970778
TI  - Association of T CD4 lymphocyte levels and subgingival microbiota of chronic
      periodontitis in HIV-infected Brazilians under HAART.
AB  - OBJECTIVE: The aim of this study was to determine the subgingival microbiota of
      HIV-infected patients with chronic periodontitis and different T CD4 lymphocyte
      levels under HAART. STUDY DESIGN: 64 HIV+ patients (mean age 34.5 +/- 7.3; 75%
      males) were distributed into Group I: chronic periodontitis (> or = 3 sites with
      probing pocket depth (PPD) and/or clinical attachment level (CAL) > or = 5 mm);
      and Group II: periodontal health (no sites with PPD > 3 mm and/or CAL > 4 mm).
      All subjects received conventional periodontal therapy. Periodontal clinical
      parameters were evaluated at 6 sites/tooth in all teeth at baseline and 4 months
      after therapy. The levels of T CD4 were obtained from the patient's medical
      record. Subgingival plaque samples were taken from the 6 sites with the largest
      pocket depth in each subject of Group I, and 6 randomly selected sites in
      subjects of Group II. The presence of 22 subgingival species was determined using
      the checkerboard DNA-DNA hybridization method. Significant microbiological
      differences within and among groups were sought using Wilcoxon signed-rank and
      Mann-Whitney tests, respectively. Relationships between T CD4 levels and
      microbiological parameters were determined using Kruskal-Wallis test. RESULTS:
      Sixty-one percent of the HIV-infected patients represented AIDS cases, although
      69% of them were periodontally healthy. The T CD4 lymphocyte mean level was 333
      cells/mm3 and viral load was 12,815 +/- 24,607 copies/mm3. Yet, the prevalence of
      chronic periodontitis was relatively low (36%). Several periodontal pathogens, in
      particular T. forsythensis (P < .05), were more prevalent in HIV-positive
      patients with periodontitis than in HIV-positive subjects with periodontal
      health. Most of the species decreased in frequency after therapy, particularly P.
      gingivalis (P < .05). E. faecalis and F. nucleatum were significantly more
      prevalent in the subgingival microbiota of patients with chronic periodontitis
      and lower levels of T CD4 (P < .05), while beneficial species tended to be more
      frequently detected in individuals with T CD4 counts over 500 cells/mm3.
      CONCLUSION: The subgingival microbiota of HIV-infected patients with chronic
      periodontitis include a high prevalence of classical periodontal pathogens
      observed in non-infected individuals. Furthermore, the severe immunosuppression
      seems to favor the colonization by these species, as well as by species not
      commonly found in the subgingival microbiota.

PMID- 14970779
TI  - Efficacy of chlorhexidine gluconate rinse for treatment and prevention of oral
      candidiasis in HIV-infected children: a pilot study.
AB  - PURPOSE: We evaluated the effect of chlorhexidine (CHX) 0.12% rinses on the
      clinical and microbiologic manifestations of oral candidiasis in HIV-infected
      children. STUDY DESIGN: This was a cross-sectional, clinical intervention study
      of 38 HIV-positive children. Inclusion in the study was based on oral examination
      and positive oral culture for Candida. At baseline, subjects with no clinical
      lesions but who were culture-positive for Candida (N = 9) were placed on
      preventive therapy of CHX q.d. for 90 days. Subjects with clinical oral
      candidiasis (N = 9) were placed on therapeutic CHX b.i.d. All 38 subjects
      received oral exams at monthly intervals. At 90 days oral mucosal samples were
      again taken for Candida. Colony-forming units (CFU) were determined before and
      after CHX treatment. RESULTS: Of 18 culture-positive subjects, 12 were included
      in the CFU analyses. After 3 months of CHX oral rinse therapy, Candida was
      undetectable in 3 children; another 8 showed an average 2-fold reduction in CFU.
      In 1 child the number of CFU increased modestly. Overall, the average pre- and
      posttreatment mean CFU was 6.18 +/- 2.19 and 2.73 +/- 3.15, respectively (P =
      .009). Five patients with clinical oral candidiasis at baseline, including all 3
      who had pseudomembranous candidiasis, were free of signs of disease at the end of
      the study. CONCLUSIONS: This study suggests that the topical disinfectant CHX may
      be a promising agent for treating and preventing oral candidiasis in HIV-infected
      children.

PMID- 14970780
TI  - Parathyroid hormone-related protein (PTHrP) expression in ameloblastoma.
AB  - OBJECTIVE: Parathyroid hormone-related protein (PTHrP) production has been
      demonstrated in a variety of tumor subtypes. Local production of PTHrP by
      metastatic tumor cells in bone has been linked to bone destruction and tumor
      growth. Ameloblastoma (AB) is a relatively common odontogenic epithelial neoplasm
      that manifests local infiltrative intraosseous growth. AB recapitulates the
      developing enamel epithelium, in which PTHrP recently has been demonstrated. Yet
      PTHrP expression in a series of ABs has not been studied to date. The purpose of
      this investigation is to assess the expression of PTHrP in ameloblastoma. STUDY
      DESIGN: Formalin-fixed, paraffin-embedded tissue sections of ameloblastoma (n =
      30; 24 conventional, 4 unicystic, and 2 arising in dentigerous cyst) were
      immunostained with anti-PTHrP antibody using a multistep streptavidin-peroxidase
      technique. Semiquantitative scoring of immunoreactivity was assessed as mild,
      moderate, and intense. RESULTS: All cases (100%) demonstrated positive
      immunoreactivity, with mild reaction in 3 conventional ABs, 1 unicystic and 1 AB
      arising in dentigerous cyst, and with moderate reaction in 12 conventional ABs, 3
      unicystic and 1 AB arising in dentigerous cyst. Intense immunoreactivity was seen
      in 9 cases of conventional AB. This difference in immunostaining was not
      statistically significant (Sigma2 = 4.41, df = 4, P = .358). CONCLUSION: The
      results of this investigation suggest that PTHrP may play a significant role in
      local bone resorption, offering at least partial explanation for the tumor's
      infiltrative growth and destructive behavior. The uniformity of PTHrP expression
      by AB, as detailed in this study, may harbor significant therapeutic
      implications, particularly through PTHrP-blocking treatment modalities.

PMID- 14970781
TI  - Phenotypic diversity and revision of the nomenclature for autosomal recessive
      amelogenesis imperfecta.
AB  - PURPOSE: The purpose of this study was to characterize the phenotype in 9
      families with autosomal recessive amelogenesis imperfecta (ARAI), and to propose
      a classification system allowing inclusion and delineation of diverse ARAI
      phenotypes. STUDY DESIGN: Nine families with ARAI were evaluated clinically and
      radiographically. Exfoliated and extracted teeth were examined via light and
      scanning electron microscopy, with the enamel in one case evaluated by amino acid
      analysis. RESULTS: The 9 families demonstrated diverse ARAI phenotypes including
      localized hypoplastic, generalized thin hypoplastic, hypocalcified and
      hypomaturation AI types. CONCLUSIONS: Some ARAI phenotypes observed in this study
      and reported in the literature cannot be classified using currently accepted ARAI
      nomenclature. Therefore, we propose a revised nomenclature permitting both
      classification of all ARAI clinical forms and inclusion of anticipated molecular
      based nomenclature, such as now exists for some X-linked and autosomal dominant
      AI subtypes.

PMID- 14970782
TI  - A prospective study on transplantation of third molars with complete root
      formation.
AB  - OBJECTIVE: The study objective was to evaluate the prognosis for
      autotransplantation of third molar teeth with fully developed roots followed by
      endodontic treatment on the basis of a time-table analysis. STUDY DESIGN: A total
      of 50 third molars with completely developed roots were autotransplanted to
      replace a lost first or second molar in the same number of admitted patients.
      Root canal treatment was started 3 to 4 weeks later. Clinical and radiographic
      checkup of the transplanted and root-filled third molars was done annually
      according to a predesigned record form. Descriptive statistics including a life
      table and statistical analysis were performed. RESULTS: The cumulative survival
      rate during 4 years' follow-up was 81.4%. In all, 7 transplants were lost during
      the follow-up time, 4 of them due to marginal periodontal pathosis and the other
      3 due to root resorption. None of the root resorptions was observed before the
      second postoperative year. The radiographic periapical status was considered
      normal in 96% of the transplants at the latest follow-up visit. CONCLUSIONS:
      Autotransplantation of mature third molar teeth is a reasonable treatment
      alternative to conventional prosthetic rehabilitation or implant treatment in
      cases of partial edentualism from both a therapeutic and an economic point of
      view.

PMID- 14970783
TI  - Emdogain promotes osteoblast proliferation and differentiation and stimulates
      osteoprotegerin expression.
AB  - PURPOSE: The purpose of this study was to investigate the effects of EMD on the
      growth and differentiation of osteoblastic cells (MC3T3-E1) and on the expression
      of osteoprotegerin (OPG), a key cytokine that inhibits osteoclastogenesis and
      osteoclast function. STUDY DESIGN: MC3T3-E1 cells were treated with 100 microg/mL
      EMD in serum-free medium for 1, 2, 3, 5, and 7 days, or in 2% fetal bovine serum
      (FBS) for 3 weeks. Cells incubated without EMD served as negative control. At the
      end of each incubation period, cell numbers were counted and total cellular mRNA
      was extracted. Northern blot analysis and RT-PCR were performed to determine the
      mRNA levels of core binding factor alpha (Cbfa1), collagen alpha1 (I), bone
      sialoprotein (BSP), osteocalcin (OC), insulin-like growth factor I (IGF-I), and
      OPG. Alkaline phosphatase (ALP) activity was also determined and compared between
      treatment and control groups. RESULTS: A marked increase in cell numbers was
      observed in EMD-treated groups from day 2 to day 7 (P < .01). mRNA expression of
      collagen alpha1 (I), BSP, OC, OPG, and IGF-I were up-regulated in cells treated
      with EMD. ALP activity was significantly increased by EMD treatment after 3-week
      culture under differentiating conditions (P < .05). The expression of Cbfa1 was
      not affected by EMD treatment from day 1 to day 5; the levels were elevated after
      culturing for 3 weeks in EMD-treated cells. CONCLUSIONS: EMD promotes both
      proliferation and differentiation of MC3T3-E1 cells and indirectly inhibits
      osteoclastogenesis and osteoclast function by stimulating the expression of OPG.

PMID- 14970784
TI  - Short-term histomorphological effects of Er:YAG laser irradiation to rat coronal
      dentin-pulp complex.
AB  - OBJECTIVE: The objective of the study was to examine the morphological changes of
      neural elements in dentin-pulp complex ultrastructurally after Er:YAG laser
      irradiation and elucidate the mechanism of pain reduction in cavity ablation.
      STUDY DESIGN: The Er:YAG laser was applied at occlusal surfaces of upper and
      lower first molar cusps of 6 rats, and shallow cavities were ablated. The dentin
      and pulps were examined with light and electron microscopes at 6 hours after the
      irradiation. Teeth, without laser irradiation, from three rats were used as
      controls. RESULTS: Disruption of nerve terminals in the dentinal tubules,
      degeneration of nerve terminals between odontoblasts, and disruption of the
      myelin sheath in the pulp core were demonstrated with electron microscope.
      CONCLUSION: Some Er:YAG laser beams could penetrate to deeper areas than ablated
      area, and damage of nerve fibers and terminals might be a mechanism of pain
      reduction in cavity ablation with Er:YAG laser.

PMID- 14970785
TI  - Cyclic fatigue testing of ProTaper NiTi rotary instruments after clinical use.
AB  - PURPOSE: The purpose of this study was to evaluate the cyclic fatigue of ProTaper
      nickel-titanium (NiTi) rotary instruments (Tulsa Dental, Tulsa, Okla) after
      multiple clinical uses. STUDY DESIGN: Two hundred twenty-five ProTaper
      instruments were divided into 3 groups: A = 75 used as controls, B = 75 used in 2
      molars (6-8 canals), and C = 75 used in 4 molars (12-16 canals). The number of
      rotations to breakage and the fractured tip length were recorded for each file
      and the mean was calculated by ANOVA. RESULTS: No S1-2 or F1-2-3 instrument
      separated during intracanal use, even if they were reused for a number of cases
      (x 4 molar cases). CONCLUSION: It is clear that prolonged reuse of NiTi rotary
      instruments strongly affects instruments' fatigue, but our data suggest the
      hypothesis that other factors (primarily errors and misuse) may be more
      accountable for intracanal instrument separation. Further studies could assess
      the cyclic fatigue of each instrument at different levels of the shaft by
      altering the radius of curvature.

PMID- 14970786
TI  - Fluid transport along gutta-percha backfills with and without sealer.
AB  - OBJECTIVE: The use of heat may influence the sealing ability of sealer. The aim
      of this study was to compare the fluid transport along the gutta-percha backfill
      portion when different sealers were used or no sealer at all. STUDY DESIGN: Four
      groups consisting of the roots of maxillary and mandibular canines were
      instrumented and obturated with vertically compacted warm gutta-percha. Down-pack
      was carried out using Touch 'n Heat (Analytic Technology, Redmond, Wash, USA) and
      prefitted pluggers. Back filling was achieved by injecting warm gutta-percha
      using Obtura II (Obtura Corporation, Fenton, Mo). In the first 3 groups, 1 of 3
      sealers was used: RoekoSeal Automix (RSA), Pulp Canal Sealer EWT (EWT), and AH26.
      In the fourth group no sealer was used. The apical root filling was removed, and
      fluid transport along the backfill portion was measured using a fluid transport
      device. RESULTS: A statistically significant difference in fluid transport was
      found among the 4 groups (P = .038). The no-sealer group recorded the highest
      fluid transport. The AH26 group was the only sealer group that displayed
      significantly less fluid transport than the no-sealer group (P = .006). The AH26
      displayed less fluid transport than the EWT group (P = .017). CONCLUSION: The
      backfills with AH26 as sealer provided a better seal than the backfills of
      injected warm gutta-percha with EWT as sealer or with no sealer at all.

PMID- 14970787
TI  - Detection and significance of the characteristic magnetic resonance signals of
      mandibular condyles in children.
AB  - OBJECTIVE: We sought to determine the magnetic resonance imaging (MRI)
      characteristics of mandibular condyles in still-growing children. In addition, we
      also evaluated the significance of the double-contour-like structure and the
      conversion from red to yellow marrow characteristic of this age. METHODS: The MRI
      characteristics of mandibular condyles were determined by means of fast spin-echo
      intermediate-weighted images in subjects 9 to 14 years old. In 1 subject who
      developed temporomandibular joint-related clinical symptoms 1 year later, MRI was
      re-performed at that time. RESULTS: With the use of MRI, a total of 17 double
      contour-like structures were detected in 42 temporomandibular joints of 9- to 14
      year-olds, but neither 50 healthy joints of youths nor adults. In terms of bone
      marrow signal changes, the turning point was found to be 11 years old. In 1
      subject, the double-contour-like structures were not visible on the MR images
      obtained 1 year after the first examination. CONCLUSION: The double-contour-like
      structure and the periods of conversion from red to yellow marrow may be able to
      be used as part of the criteria for the staging of mandibular condyle development
      in children.

PMID- 14970788
TI  - Benign fibrous histiocytoma in the mandible.
AB  - PURPOSE: Benign fibrous histiocytoma (BFH) is a very rare benign tumor occurring
      in the jaw. The purpose of this article is to describe the clinical,
      radiographic, and microscopic appearance of BFH occurring in the mandible. STUDY
      DESIGN: A 42-year-old man had an asymptomatic swelling of the left mandibular
      posterior area. RESULTS: Conventional radiographs revealed a well-defined
      multilocular radiolucency involving the left mandibular body, ramus, coronoid
      process, and condylar head. The lesion showed the thinning and expansion of the
      cortex. There were many thin, indistinct septa in the lesion. The computed
      tomography (CT) scans showed bone destruction with marginal sclerosis and a
      heterogeneous soft-tissue mass expanding the mandible. Microscopic examination
      revealed a cellular tumor composed of uniform spindle-shaped cells arranged in a
      storiform pattern. CONCLUSIONS: BFH is a very rare benign tumor occurring in the
      jaw, so more cases should be reported to understand the characteristics of the
      lesion.

PMID- 14970789
TI  - Mirror image condylar hyperplasia in two siblings.
AB  - A Hispanic family with an unusual clinical and radiological pattern of condylar
      hyperplasia is presented. Mirror images of condylar hyperplasia, malocclusion of
      teeth, and shift of midline of the mandible were seen in two brothers. The father
      had a similar abnormality of his left mandibular condyle. The condylar
      hyperplasia in this family indicates that mandibular condylar hyperplasias could
      be genetic in origin, possibly Y-linked or autosomal dominant.

PMID- 14970790
TI  - Inflammatory paradental cyst (IPC) in the mandibular premolar region in children.
AB  - OBJECTIVES: We investigated the occurrence of inflammatory paradental cysts (IPC)
      in the mandibular premolar, and demonstrated the points of difference with regard
      to diagnostic features between IPC and dentigerous cysts (DC). MATERIAL AND
      METHODS: We analyzed the radiographs and histology of 60 cases with a cystic
      lesion associated with inflammation in the mandibular premolar region based on
      diagnostic criteria as IPC. RESULTS: In 4 out of 60 cases, we diagnosed the 4
      cysts as IPCs in the mandibular premolar region, and recognized that one form of
      IPC was similar to a mandibular infected buccal cyst. The other 56 non-IPC cases
      were diagnosed as DC. On the IPCs, the permanent tooth normally erupted in all 4
      cases after treatment, but in one case, the IPC recurred. CONCLUSIONS: The
      present investigation suggested that we might have misdiagnosed IPCs in the
      mandibular premolar region as DC to date. It is important to consider the
      differences between IPC and DC with regard to the causes of recurrence during
      treatment of IPC.

PMID- 14970791
TI  - Ocular torsion: rotations around the "WHY" axis.
AB  - BACKGROUND: Traditional teaching holds that there is a partial compensatory
      countertorsion after head tilt because the intorters in the eye on the side of
      the head tilt and the extorters in the contralateral eye are stimulated. This
      teaching is inconsistent with a number of clinical observations. METHODS: Review
      of existing literature, reanalysis of data from the investigator's previous
      experiments, and inductive and deductive reasoning were used to reconcile
      inconsistencies and present a theory on why torsional movements occur. RESULTS:
      The inconsistencies can be reconciled if one considers that during the dynamic
      phase of head tilt, there is an alternating series of intorsional and extorsional
      movements of both eyes. Each eye has slow dynamic compensatory counterrolling
      phases that serve as torsional "doll's-head" movements to stabilize the image
      during head tilt. This counterrolling is partially eliminated by a series of
      anticompensatory torsional saccades in the direction of head tilt, which is in
      contrast to traditional teaching. CONCLUSION: Dynamic compensatory counterrolling
      occurs during head tilt. It is largely eliminated by anticompensatory torsional
      saccades in the opposite direction so that by the end of head tilt only minimal
      static countertorsion remains. The dynamic compensatory counterrolling motion is
      necessary to minimize peripheral visual movement during head tilt. The
      elimination of most of the counterrolling by the end of head tilt is necessary to
      preserve convergence and stereopsis.

PMID- 14970792
TI  - Maintenance of certification and the pediatric ophthalmology knowledge base.

PMID- 14970793
TI  - Ocular motility dysfunction associated with chemotherapeutic agents.

PMID- 14970794
TI  - Pediatric ophthalmology and strabismus in India.

PMID- 14970795
TI  - Traumatic optic neuropathy in children and adolescents.
AB  - PURPOSE: Retrospective review to describe the features and visual outcome of
      traumatic optic neuropathy (TON) in children and adolescents. METHODS:
      Interventional and observational case series of children <18 years with TON.
      RESULTS: Forty children, 24 boys and 16 girls, were identified with 43 affected
      eyes. The mean age was 11.6 years (range, 2 to 18). The most common causes were
      motor vehicle accidents (62%) and sports injuries (22%). The trauma was blunt in
      78% of cases and penetrating in 22%. Visual acuity at presentation for 27
      patients whose visual acuity could be assessed ranged from no light perception to
      20/80. Interventions included corticosteroids (n = 18), decompression of the
      optic canal (n = 3), and optic sheath nerve fenestration (n = 1). Visual outcome
      for 22 children with at least 1 month of follow-up was no light perception in 10
      (45%), < 20/200 in 7(32%), 20/200 to < 20/80 in 1(4%), and > or = 20/80 in 4
      (18%). There was no difference in the rate or degree of improvement between
      treated and untreated patients. CONCLUSION: TON in children is caused by
      mechanisms similar to those that cause TON in adults. The severity of visual loss
      as well as the rate and degree of improvement are also similar. Our data do not
      indicate that treatment improves visual outcome.

PMID- 14970796
TI  - Maximum angle of horizontal strabismus consistent with true stereopsis.
AB  - BACKGROUND: We prospectively evaluated the performance of three stereoacuity
      tests in patients with a wide range of strabismus angles to determine the maximum
      angle of horizontal strabismus consistent with true stereopsis as well as the
      extent of false-positive results. METHODS: Subjects age > or = 5 years old (n =
      186) with constant horizontal strabismus were prospectively studied. Stereoacuity
      was measured using the Titmus Fly, Animals, and Circles tests; the original
      Preschool Randot test; and the Frisby test. We defined a false-positive result as
      any positive response to a stereoacuity test when a patient had > 20 prism
      diopters (PD) of deviation. Based on the results from our previous study of
      monocularly patched adults, we then defined a true-positive result as Titmus
      circles five to nine, at least 400" on the original Preschool Randot test, or a
      pass on the Frisby test. Data were then analyzed to determine a maximum deviation
      consistent with true stereopsis. RESULTS: False-positive results occurred with
      Titmus Fly (6%), Titmus Animals (10%), Titmus Circles (35%), and the 800 seconds
      of arc (") level of the original Preschool Randot test (10%). No false-positive
      results were seen with the Frisby test. Applying the criteria for a true-positive
      result, we found that no patient with > 10 PD of deviation had true stereopsis.
      The two patients with 10 PD and 6 PD deviations could not subsequently pass the
      Frisby test and were therefore deemed not to have true stereopsis. We concluded
      that the threshold for true stereopsis may be as low as 4 PD of horizontal
      deviation. CONCLUSION: In summary, the Titmus Fly, Titmus Animals, and Titmus
      Circles (the first four circles) tests possess monocular clues that limit their
      usefulness for clinical testing. The Frisby test is particularly useful for rapid
      assessment of whether stereopsis is present or absent. The new Preschool Randot
      test is valuable for quantifying stereopsis in both children and adults. True
      stereopsis may be rare when a patient has a horizontal deviation > 4 PD.

PMID- 14970797
TI  - Outcome study of the development of fusion in patients aligned for congenital
      esotropia in relation to duration of misalignment.
AB  - PURPOSE: The results of recent studies have shown that the presence and quality
      of stereopsis in patients with congenital esotropia and subsequent surgically
      alignment are dependent upon the duration of the misalignment during the first 2
      years of life. The purpose of this study was to investigate the presence of
      fusion in patients with different durations of misalignment whose eyes were
      aligned at different ages by age 2 years. METHODS: Data previously obtained in a
      study of 90 patients with congenital esotropia aligned by 2 years of age,
      examined in a masked independent evaluation for binocularity, were analyzed.
      Patient age at alignment and duration of misalignment were correlated with the
      presence of fusion. RESULTS: Fusion was present in 94% of all patients aligned by
      age 2 years and in 94% of patients with < or =21 months of misalignment. There
      was no statistically significant difference between those aligned by 6, 12, or 24
      months (P > 0.05, power = 0.8). No significant difference was found between those
      aligned with duration of misalignment < or = 6, between 7 and 12, or between 13
      and 21 months. CONCLUSION: Unlike the findings of stereopsis studies, there was
      no significant difference in the proportion of patients who achieved fusion in
      congenital esotropes who had up to 21 months of misalignment and whose eyes were
      aligned at different ages within the first 24 months of life.

PMID- 14970798
TI  - Ocular motility disturbances after episcleral plaque brachytherapy for uveal
      melanoma.
AB  - OBJECTIVE: To evaluate contributions of various factors in the development of
      strabismus after iodine-125 brachytherapy for uveal melanoma. METHODS: Twenty
      consecutive patients who underwent episcleral plaque brachytherapy for uveal
      melanoma underwent a full orthoptic examination before and after the surgery.
      Iodine-125 seeds at 5-mCi strengths were used with a mean total dose of 10.400
      cGy toward the tumor apex. RESULTS: Average follow-up time was 25.4 months
      (range, 14 to 40). At 12 months all tumors showed regression, 9 patients had
      visual acuity of 20/200 or better, and 4 patients had ambulatory vision. After
      tumor treatment, 8 patients were orthophoric, 9 patients developed exotropia, 1
      patient became hypertropic, 2 patients developed exotropia and hypertropia. Of 2
      patients who developed significant diplopia, 1 received 10 U botulinum-toxin A
      injection (Botox, Allergan, Irvine, CA) for exotropia, and the other was managed
      with superior rectus advancement and superior oblique tenectomy for surgery
      induced iatrogenic Brown's syndrome and slipped superior rectus muscle.
      CONCLUSION: Extensive mechanical injury, possible ionizing radiation of the
      plaques, and low visual acuity may cause strabismus after episcleral plaque
      brachytherapy. Diplopia and cosmesis could be improved with Botox injection or
      strabismus surgery.

PMID- 14970799
TI  - The effect of Seprafilm on adhesions in strabismus surgery-an experimental study.
AB  - PURPOSE: Seprafilm (Genzyme, Cambridge, MA) is a bioabsorbable membrane composed
      of sodium hyaluronate and carboxymethylcellulose. Adhesions occurring after
      strabismus surgery may affect surgical outcome. The purpose of our study was to
      histopathologically evaluate the influence of Seprafilm on postoperative
      adhesions. METHODS: Seven adult male New Zealand albino rabbits were used. The
      superior rectus muscle was resected 3 mm, and a fornix-based limbal conjunctival
      dissection was made inferonasally in both eyes. In one eye of each rabbit,
      Seprafilm was inserted between the conjunctiva and superior rectus and under the
      dissected inferonasal conjunctiva. The fellow eye of each rabbit, having
      undergone superior rectus resection and inferonasal conjunctival dissection
      without Seprafilm, served as the control group. The rabbits were killed and the
      eyes were enucleated at 6 weeks after surgery. Histopathological sections were
      analyzed for inflammation and fibrosis by staining them with hematoxylin-eosin
      and Masson trichrome, respectively. Inflammation and fibrosis were graded on a
      scale of 0 to 4. RESULTS: Compared with the control eyes, there was no
      significant difference with regard to inflammation either at the area of superior
      rectus resection or the area of conjunctival dissection (P.655 and P.157,
      respectively). Significantly less fibrosis occurred in the surgical areas where
      Seprafilm was used compared with the control group (P.046 and P.015,
      respectively) both at the area of superior rectus resection and the area of
      conjunctival dissection. CONCLUSION: This study shows that Seprafilm
      significantly decreases postoperative adhesions between the conjunctiva, muscle,
      and sclera. Application of Seprafilm may prove useful in strabismus surgery
      especially where adhesion formation may influence the outcome and in cases where
      recurrent conjunctival dissection may be needed.

PMID- 14970800
TI  - Long-term follow-up of eye growth in pediatric patients after unilateral cataract
      surgery with intraocular lens implantation.
AB  - PURPOSE: To evaluate the refractive status, axial length, and refractive power of
      the cornea in pediatric patients after unilateral cataract surgery and
      intraocular lens implantation. METHODS: Refractive state, refractive power of
      cornea, and axial length were measured both in the operated and nonoperated eyes
      in 15 patients (age at surgery = 5 to 15 years; mean, 10.3) before and 4 to 15
      years (mean, 9.7) after unilateral cataract surgery. RESULTS: After surgery,
      visual acuity was 20/40 or better in 79% of operated eyes. Myopic changes,
      representing the difference between postoperative refraction at last follow-up
      and postoperative refraction at 1 year after surgery, were noted in the operated
      eyes at the end of study (mean, -5.02 D), but there were no significant
      differences in axial length (Wilcoxon signed rank test P >.05) or refractive
      power of the cornea between operated and nonoperated eyes (paired Student t test
      P >.05). CONCLUSION: Myopic shift after cataract surgery with intraocular lens
      implantation may occur even in older children.

PMID- 14970801
TI  - Factors influencing the outcome of strabismus surgery in patients with exotropia.
AB  - PURPOSE: To determine the factors associated with favorable and less favorable
      outcomes in strabismus surgery for treatment of exotropia and to show the factors
      influencing the efficacy of the surgical procedure. METHODS: Case files of 225
      patients with a diagnosis of primary exotropia were evaluated. Information about
      patient age at onset of deviation, patient age at surgery, interval between onset
      and surgery, preoperative deviation, refractive errors, degree of anisometropia,
      visual acuity, presence of amblyopia, presence of an A- or a V-pattern, amount of
      surgery performed, type of exotropia (intermittent or constant), and existence of
      binocular single vision before surgery were obtained and evaluated using multiple
      regression analysis. RESULTS: Preoperative deviation and refractive errors were
      proved to be significant factors influencing a favorable outcome in patients with
      surgically treated exotropia (r(2) = 0.12, P <.001, and r(2) = 0.07, P <.001
      respectively). Preoperative deviation, amount of surgery performed, and
      refractive errors shifting toward myopia significantly influenced the efficacy of
      the surgery performed (r(2) = 0.31, 0.06, and 0.025, respectively). CONCLUSION:
      Special care should be paid to refractive errors in patients with exotropia
      before determining the amount of surgical intervention.

PMID- 14970802
TI  - Optic nerve hypoplasia with intracranial arachnoid cyst.
AB  - BACKGROUND: The frequent association between optic nerve hypoplasia (ONH) and
      other central nervous system abnormalities has been widely reported in the
      literature. Occasional reference has been made to arachnoid cyst as one of the
      associated findings. METHOD: The charts and neuroradiologic findings of the 40
      patients with ONH seen in our department as well as the Visually Impaired Program
      during the past 8 years were reviewed. RESULTS: An intracranial arachnoid cyst
      was present in 5 of the 40 patients (12.5%) with ONH and visual impairment. These
      patients' clinical and neuroradiologic findings are reported here. CONCLUSION:
      The presence of an intracranial arachnoid cyst in a patient with hypoplastic
      optic nerves could occur as a coincidental association between these lesions.
      Alternatively, a common mechanism could give rise to both abnormalities. Three
      such possibilities-including damage to the developing visual pathway by the
      arachnoid cyst, absence of an axonal guidance molecule similar to netrin-1
      identified in the mouse, or a common genetic mutation involving the myocillin
      gene causing both abnormalities-are considered.

PMID- 14970803
TI  - Acute sixth-nerve palsy after vincristine therapy.
AB  - The chemotherapeutic effectiveness of vincristine was first reported in 1962, and
      with its increased use the incidence of reported neurologic side effects has also
      increased. We reported a case of acute sixth-nerve palsy occurring soon after
      administration of vincristine for acute lymphoblastic leukemia (ALL), a
      previously unreported side effect.

PMID- 14970804
TI  - Isolated abducens nerve palsy induced by vincristine therapy.
AB  - We report a 28-year-old man with non-Hodgkin's lymphoma who presented with acute
      onset of diplopia 3 weeks after the completion of combination chemotherapy with
      vincristine. He had a left esotropia with marked decrease in abduction. Magnetic
      resonance imaging scan of the brain showed thickening and enhancement of the left
      abducens nerve. Lymphomatous and other intracranial pathologies were excluded,
      and vincristine neurotoxicity was considered as the possible etiology of the
      abducens nerve palsy. His diplopia improved gradually, then completely resolved 4
      weeks after the cessation of vincristine therapy. We concluded that isolated
      ocular muscle paresis can be the presenting sing of a toxic neuropathy associated
      with vincristine use.

PMID- 14970805
TI  - Late-onset progressive strabismus associated with a hydrogel scleral buckle.
AB  - A hydrophilic implant for scleral buckling was developed in 1980. Advantages
      include softness and elasticity, no dead spaces, ability to gradually absorb and
      release antibiotics, and stimulating production of a fibrous capsule around the
      implant. Short-term fellow studies in rabbits showed no clinical or histologic
      complications. Long-term complications of the hydrogel scleral buckle have
      emerged in the las 10 years. These included fragmentation, subconjunctival
      bulging, intraocular erosion, migration, and restriction of extraocular movement.
      We recently encountered a patient with progressive restrictive strabismus
      beginning 8 years after retinal detachment repair with a MIRAgel (hydrogel; MIRA,
      Uxbridge, MA) scleral buckle. Worsening complaints of diplopia and discomfort led
      to strabismus surgery. Untreatable retinal detachment resulted in enucleation.

PMID- 14970806
TI  - Collaborative surgical treatment of breast cancer.

PMID- 14970807
TI  - The impact of non-injury-related factors on disability secondary to whiplash
      associated disorder type II: a retrospective file review.
AB  - BACKGROUND: There is evidence to suggest that Whiplash Associated Disorders
      (WADs) are influenced by physical trauma and psychosocial factors, as well as by
      medicolegal and compensation systems. OBJECTIVE: To investigate the impact of
      noninjury related variables on self-reported disability at initial assessment
      among patients presenting with WAD type II injuries. DESIGN AND SETTING: We
      reviewed a total of 1101 consecutive files of patients presenting to a single
      chiropractor's office in British Columbia, Canada. We included those who met the
      inclusion criteria. We extracted demographic variables and noninjury related
      information from 33 eligible patient files. We calculated correlations between
      variables and created a multivariable linear regression model to evaluate their
      relative associations with Neck Disability Index (NDI) scores on presentation.
      RESULTS: Higher NDI scores on initial assessment correlated with female sex (r =
      0.40, P =.02), a greater number of subsequent treatments (r = 0.44, P =.01), a
      higher number of providers seen before presentation (r = 0.40, P =.02), and most
      strongly with the involvement of a lawyer (r = 0.73, P <.01). A multivariable
      linear regression model found that only female sex (P =.03) and the involvement
      of a lawyer (P =.01) remained significantly associated with higher NDI scores on
      presentation (adjusted R2 = 0.68 for the model). Female sex was associated with a
      10-point increase in NDI scores on presentation (beta coefficient = 10.5; 95%
      confidence interval [CI] 2.8-18.2), and involvement of a lawyer was associated
      with a 15-point increase in NDI scores on presentation (beta coefficient = 14.9;
      95% CI 5.0-24.7). CONCLUSION: Our analysis of WAD type II patients in receipt of
      compensation found that higher self-reported disability on initial assessment was
      associated with female sex and in particular by retaining a lawyer. Large
      prospective studies are needed to establish the validity of these findings.

PMID- 14970808
TI  - The interexaminer reproducibility of physical examination of the cervical spine.
AB  - OBJECTIVE: To assess the interexaminer reproducibility of physical examination of
      the cervical spine. METHODS: Two physiotherapists independently judged the
      general mobility and the intersegmental mobility (segments C0-T2) of the neck and
      the pain that was provoked. Percentage agreement and Cohen's kappa expressed
      agreement of dichotomous variables; limits of agreement expressed agreement of
      continuous variables; and intraclass correlation coefficients (ICCs) expressed
      the reliability of continuous variables. RESULTS: Agreement for general mobility
      showed kappa between 0.05 and 0.61, and for the intersegmental mobility, it
      showed kappa values between -0.09 and 0.63. Agreement for provoked neck pain
      within 1 point of an 11-point numerical rating scale (NRS) varied between 46.9%
      and 65.7% for general mobility and between 40.7% and 75.0% for intersegmental
      mobility. The ICCs varied between 0.36 and 0.71 for general mobility and between
      0.22 and 0.80 for intersegmental mobility. CONCLUSIONS: Despite the use of a
      standardized protocol to assess general mobility and intersegmental mobility of
      the cervical spine, it is difficult to achieve reasonable agreement and
      reliability between 2 examiners. Likewise, the patients are not able to score the
      same level of provoked pain in 2 assessments with an interval of 15 minutes.

PMID- 14970809
TI  - The reliability of quantifying upright standing postures as a baseline diagnostic
      clinical tool.
AB  - OBJECTIVE: To assess the reliability of posture across and within subjects,
      specifically the repeatability of spinal angles determined by digitization of
      images in the anterior, posterior, and sagittal views. DESIGN: A repeated measure
      design was used in which subjects were required to attend 3 sessions, each
      consisting of 3 trials. Photographs of the anterior, posterior, and lateral views
      of normal, relaxed upright standing were taken during each trial. Landmarks were
      digitized and cervical, thoracic, and lumbar angles were calculated with respect
      to a vertical reference line. SUBJECTS: Fourteen healthy and active subjects (7
      male subjects and 7 female subjects) were recruited from a university student
      population. All had been free of low back pain during the previous 6 months.
      RESULTS: When comparing mean angles, no significant differences were detected for
      any angle in any view. However, large variability within subjects was observed,
      likely leading to the lack of significance found with respect to the main factors
      in the analysis of variance (ANOVA). Large coefficients of variance (CVs) reflect
      the substantial intrasubject variability, as well as poor to moderate agreement
      indicated by intraclass correlation coefficients (ICCs). There were no apparent
      trends indicating that gender affected repeatability of posture. CONCLUSIONS: The
      poor repeatability of postures documented using the studied method brings into
      question the validity of this postural analysis approach for either diagnostic
      use or tracking changes in response to treatment. Users of such postural analysis
      tools should interpret postural deviations from a vertical reference with
      caution, as there are many inherent factors that can contribute to the
      variability of these measured postures.

PMID- 14970810
TI  - Reliability of the motor evoked potentials elicited through magnetic stimulation
      at three sites.
AB  - BACKGROUND: Motor evoked potentials (MEPs) obtained from magnetic stimulation
      allow the measurement of the excitability of motor nerve cells. Although this
      technique is becoming widely used, its reliability has yet to be established.
      OBJECTIVE: To determine the reliability of MEPs and evaluate their stability.
      DESIGN: Subjects received magnetic stimulation at 3 different sites: cranial,
      cervical, and peripheral. Three stimulations were given at each site.
      Stimulations were given under 4 conditions: eyes open or closed and with or
      without controlled mental activity. SETTING: The study was performed in a
      research laboratory setting. PARTICIPANTS: Nine healthy subjects (mean age = 21
      years +/- 0.9), asymptomatic of any neural or musculoskeletal dysfunctions. MAIN
      OUTCOME MEASURES: Normalized peak-to-peak amplitude of MEPs at the opponens
      pollicis muscle. RESULTS: Intraclass correlations were high for all conditions (R
      > 0.90). The amplitude of the MEPs elicited from the transcranial site during the
      controlled mental activity condition was increased by 26.6% (P =.017). No other
      significant differences (P >.05) were obtained among the other conditions.
      CONCLUSION: Intraclass correlation results reveal that MEP measurements are
      highly reliable in a controlled environment. The increase of MEPs during the
      controlled mental activity condition could be attributed to an elevation of
      neural activity of different nonmotor areas of the brain increasing corticospinal
      excitability.

PMID- 14970811
TI  - An exploratory study of provocation testing with padded wedges: can prone
      blocking demonstrate a directional preference?
AB  - BACKGROUND: Currently, no traditional chiropractic examination method to
      determine a spinal listing offers demonstrated guidance in treatment decisions
      for low back pain (LBP) patients. Development of an examination that bypasses the
      difficulty of accurately and reliably identifying a listing, yet provides
      guidance on manipulative vectors, could be very valuable to clinicians and
      patients. OBJECTIVE: To explore 2 potential protocols for provocation testing and
      assessment of directional preference using padded wedges. METHODS: Two groups of
      20 subjects were examined while lying prone on various positions of padded
      wedges. In the first group, pain pressure threshold (PPT) was measured at 4
      anatomic points; in the second group, tenderness was measured at 1 anatomic
      point. We investigated whether either method could demonstrate a directional
      preference response. RESULTS: When tenderness was measured at 1 anatomic point,
      70% of subjects demonstrated a directional response, and only 1 subject exhibited
      an increase in baseline tenderness at the end of the procedure. When PPT was
      measured at 4 anatomic points, 40% of subjects demonstrated a directional
      response, but 12 subjects exhibited decreased PPT at the end of the procedure.
      CONCLUSION: Measuring changes in tenderness at 1 anatomic point in response to
      various padded wedge patterns appears promising as an examination procedure to
      determine directional preference.

PMID- 14970812
TI  - Stability of paraspinal thermal patterns during acclimation.
AB  - BACKGROUND: Paraspinal thermography has been used by chiropractors since 1924.
      One method of its interpretation is with the use of "pattern analysis"-a method
      that assesses temperature differentials (patterns). This, in turn, theoretically
      provides information about nervous system function. When a warm back is exposed
      to the cooler air in the examining room, the skin temperature, in general, drops
      but the differentials could remain fairly constant. OBJECTIVE: To determine what
      changes occur in paraspinal heat patterns when the back is exposed to room
      temperature. STUDY DESIGN: Observational; measures repeated at 5-minute intervals
      for 31 minutes. METHODS: Thirty subjects were scanned with digital infrared
      thermographic instrumentation every 5 minutes over a 31-minute period for a total
      of 7 readings. A computerized calculation of percent similarity between
      consecutive comparisons of the readings was then performed to determine if and
      when the pattern stabilized. RESULTS: Cervical spine temperatures remained
      constant while lower back temperatures, in general, decreased for the entire 31
      minute recording period. Although the results varied among subjects, on the
      average, the patterns stabilized after 16 minutes. CONCLUSIONS: Once the
      patient's back is exposed to cooler room temperature, the skin temperature
      decreases constantly for 31 minutes; however, the pattern becomes stable after 16
      minutes. Readings taken for the purpose of pattern analysis during this 16-minute
      period may be unreliable for some patients. Therefore, a 16-minute acclimation
      period is recommended. Further research is needed to not only verify this finding
      with the same equipment in a separate experiment but to verify it as well with
      other types of temperature instrumentation.

PMID- 14970813
TI  - Deforming lipoblastomatosis of the lower extremity.
AB  - OBJECTIVE: Lipoblastomatosis is a rare disorder in infants and children and
      nonexistent in adults. We discuss a case of a newborn child with
      lipoblastomatosis extensively involving the pelvis and lower extremities. The
      clinical and radiological characteristics of the disorder are discussed. CLINICAL
      FEATURES: A 2-month-old male had an enlarging deformity of the pelvis and lower
      extremities with progression of the condition from birth. There was no family
      history related to the disease. No other clinical abnormalities were present.
      INTERVENTION AND OUTCOME: Lipoblastomatosis is initially treated with surgical
      excision of the lipomatous neoplastic tissue. The postsurgical outcome is
      satisfactory; however, the likelihood of recurrence has been reported.
      CONCLUSION: We present the features of lipoblastomatosis, an uncommon disorder
      affecting infants and children. The clinical and radiologic manifestations of the
      disease are assessed with emphasis on magnetic resonance imaging.

PMID- 14970814
TI  - Spontaneous cervical artery dissections and implications for homocysteine.

PMID- 14970815
TI  - Lateral cervical curve changes in patients receiving chiropractic care after a
      motor vehicle collision: a retrospective case series.

PMID- 14970816
TI  - Barriers to expanding primary care roles for chiropractors: The role of
      chiropractic as primary care gatekeeper.

PMID- 14970817
TI  - Does the adjustment cavitate the targeted joint? An investigation into the
      location of cavitation sounds.
AB  - BACKGROUND: The cavitation sounds heard during chiropractic adjustments of the
      spine are common phenomena; yet, their location relative to the technique used is
      relatively untested. OBJECTIVE: The purpose of this study was to locate the
      cavitation sounds during the L5 spinous hook adjustment and a lower sacroiliac
      adjustment. The sounds were analyzed for significant difference in location
      relative to the 2 techniques. METHODS: Thirty asymptomatic volunteers were
      randomly divided into 2 equal groups. Each group represented either the spinous
      hook adjustment or lower sacroiliac adjustment. Subjects had 8 microphones taped
      to their skin, over the relevant facet and sacroiliac joints. Radiographic
      confirmation was used to ensure optimal placement of the microphones. Sound
      signals produced during the adjustments were digitized, recorded, and analyzed
      statistically. RESULTS: The results indicated that no statistically significant
      correlation existed between the anatomical location of cavitation sounds and the
      adjustment technique selected. CONCLUSION: Location of cavitation sounds does not
      appear to have a relationship with type of manipulative technique selected.
      Further studies using other techniques need to be performed.

PMID- 14970818
TI  - Far-lateral disk herniation: case report, review of the literature, and a
      description of nonsurgical management.
AB  - OBJECTIVE: To review the history and examination of a far-lateral lumbar
      intervertebral disk herniation (FLLIDH), as well as the treatment and outcomes of
      a nonsurgical approach. CLINICAL FEATURES: A 60-year-old healthy male subject had
      a 3-week history of right buttock and calf pain. He initially had a left lateral
      list and asymmetrical pelvic landmarks. Range of motion (ROM) of the lumbar spine
      revealed full and pain-free lumbar flexion, right-sided pain with lumbar
      extension and left side bending, and painful and restricted left side bending.
      Neurologic examination was unremarkable. INTERVENTION AND OUTCOME: The patient
      was treated with a lumbar epidural and nerve root injection, as well as
      manipulation. Physical therapy consisted of deweighting treadmill, autotraction,
      and strengthening exercises. Outcomes were measured by using the Modified
      Oswestry Questionnaire, as well as a numerical pain rating scale. His initial
      Oswestry was 73%, pain 9/10 at presentation. Upon discharge, the Oswestry was 0%
      and pain was rated as 0/10. CONCLUSION: A significant decrease was noted in both
      the Oswestry Questionnaire, as well as the pain rate. The patient returned to
      running on alternate days for a minimum of 30 minutes, which was his primary
      goal. This case demonstrated a positive outcome using a multidisciplinary
      approach in a patient diagnosed with a FLLIDH. He obtained his goals and his
      function was fully restored.

PMID- 14970819
TI  - The evolution of genetic regulatory systems in bacteria.

PMID- 14970820
TI  - The art and design of genetic screens: mammalian culture cells.

PMID- 14970821
TI  - Maximizing the potential of functional genomics.

PMID- 14970822
TI  - Domestic-animal genomics: deciphering the genetics of complex traits.

PMID- 14970823
TI  - Ontologies in biology: design, applications and future challenges.

PMID- 14970824
TI  - A new approach to the distribution and storage of genetic resources.

PMID- 14970825
TI  - Expression profiling--best practices for data generation and interpretation in
      clinical trials.

PMID- 14970826
TI  - Patient attitudes towards surgically implantable, long-term delivery of
      psychiatric medicine.
AB  - The introduction of surgically implantable medication delivery systems provides
      psychiatric patients with reversible, uninterrupted access to medication for up
      to 14 months. This study designed and administered a survey to assess patients'
      attitudes and beliefs towards illness, medication, and this potential new
      treatment method. The survey included questions about demographics, insight and
      attitudes towards illness, current and past medication adherence, attitudes
      towards psychiatric and nonpsychiatric medications, and understanding and
      attitudes towards surgical implants. The sample of 206 psychiatric patients was
      almost equally split between favorably and unfavorably considering implants.
      Patients favorable towards implants ascribed forgetting and failure to refill
      medication on time as the reasons for missing doses, recognized the benefits of
      medication in general, and understood that the implant would be inserted under
      the skin. Favorable consideration of implants was positively correlated with the
      desire to avoid adverse consequences of missing medicine, stay well, avoid the
      need for daily oral medications, and decrease family burden. Unfavorable
      consideration of implants was related to a preference to take medication orally,
      concern about feeling controlled, unwillingness to try something new, and not
      understanding that the implant would be placed under the skin. Demographic
      variables, past/current medications, specific diagnosis, and illness severity did
      not influence the decision. This survey elucidates patients' attitudes and
      beliefs towards illness, medication, and surgical implants. The results indicate
      that a significant proportion of patients recognize the difficulties of
      medication adherence and the need for better methods to attain therapeutic
      response. Thus, the study provides impetus for future work in this area.

PMID- 14970827
TI  - Nicotine improves sustained attention in mice: evidence for involvement of the
      alpha7 nicotinic acetylcholine receptor.
AB  - In humans, nicotine has been shown to improve attention in both normal and
      impaired individuals. Observations in rats reflect some, but not all aspects of
      the nicotine-induced improvements in humans. To date these findings have not been
      replicated in mice. To examine the effect of nicotine on sustained attention in
      mice, we have established a version of the 5-choice serial reaction-time (5-CSR)
      task with graded levels of difficulty, based upon spatial displacement and a
      variable intertrial interval. Using this paradigm, microgram doses of nicotine
      produced a consistent reduction in the level of omissions and an improvement in
      proportion correct in normal mice. This improvement in sustained attention was
      made irrespectively of whether mice had previously received nicotine. In an
      attempt to elucidate which nicotinic acetylcholine receptor (nAChR) subtype(s)
      mediate this effect, we examined the performance of alpha7 nAChR knockout (KO)
      mice in the 5-CSR task. alpha7 nAChR KO mice not only acquired the task more
      slowly than their wild-type littermates, but on attaining asymptotic performance,
      they exhibited a higher level of omissions. In conclusion, by increasing the
      level of task difficulty, the performance of mice was maintained at sufficiently
      low levels to allow a demonstrable improvement in performance upon nicotine
      administration. Furthermore, as alpha7 KO mice are clearly impaired in the
      acquisition and asymptotic performance of this task, the alpha7 nAChR may be
      involved in mediating these effects of nicotine.

PMID- 14970828
TI  - Spatial memory deficits induced by perinatal treatment of rats with PCP and
      reversal effect of D-serine.
AB  - It has been suggested that perinatal treatment with the noncompetitive N-methyl-D
      aspartate (NMDA) receptor antagonist phencyclidine (PCP) induces transient
      neurodegeneration in the limbic and cortical structures of rats. Since
      dysfunction of these structures is associated with cognitive deficits in patients
      with schizophrenia, we studied the effects of subchronic treatment with PCP in
      perinatal rats with respect to spatial reference, reversal, and spatial working
      memories using the Morris water maze task in adulthood. In addition, we
      investigated the effect of D-serine, which has clinical relevance for the
      treatment of cognitive deficits in patients with schizophrenia. Our goal was to
      develop a neurodevelopmental model with predictive validity for the cognitive
      dysfunction described in patients with schizophrenia. Male and female Sprague
      Dawley rats were treated with either saline or PCP (8.7 mg/kg s.c.) on days 7, 9,
      and 11, postnatal, and the long-term behavioral effects were investigated in
      adulthood. Male PCP-treated rats were slightly impaired during the spatial
      reference memory task, but strongly impaired during the reversal and spatial
      working memory tasks. Female rats were not significantly affected by this
      treatment. This cognitive deficit was reversed by chronic treatment with D
      serine. We suggest that this model mimics some of the cognitive deficits of
      patients with schizophrenia and might be appropriate for the screening of
      putative antipsychotic agents for the treatment of these cognitive deficits.

PMID- 14970829
TI  - Prepulse inhibition and habituation of acoustic startle response in male MDMA
      ('ecstasy') users, cannabis users, and healthy controls.
AB  - Chronic administration of 3,4-methylenedioxymethamphetamine (MDMA) is associated
      with long-term depletion of serotonin (5-HT) and loss of 5-HT axons in the brains
      of rodents and nonhuman primates. Despite the broad database concerning the
      selective serotonergic neurotoxicity of recreational MDMA consumption by humans,
      controversy still exists with respect to the question of whether the well-known
      functional consequences of these neurotoxic effects, such as memory impairment,
      were caused by chronic 5-HT deficiency. Habituation and prepulse inhibition (PPI)
      of the acoustic startle response (ASR) can be used as a marker of central
      serotonergic functioning in rodents and humans. Thus, we investigated the
      functional status of the central serotonergic system in chronic but abstinent
      MDMA users by measuring PPI and habituation of ASR. PPI and habituation of ASR
      were measured in three groups. The first group (MDMA group) included 20 male drug
      free chronic users of MDMA; the second group (cannabis group) consisted of 20
      male drug-free chronic users of cannabis; and the third group (healthy controls)
      comprised 20 male participants with no history of illicit drug use. Analysis
      revealed significantly increased PPI of MDMA users compared to those of cannabis
      users and healthy controls. Cannabis users and healthy controls showed comparable
      patterns of PPI. There were no differences in habituation among the three groups.
      These results suggest that the functional consequences of chronic MDMA use may be
      explained by 5-HT receptor changes rather than by a chronic 5-HT deficiency
      condition. Use of cannabis does not lead to alterations of amplitude,
      habituation, or PPI of ASR.

PMID- 14970830
TI  - Identification of genes regulated by memantine and MK-801 in adult rat brain by
      cDNA microarray analysis.
AB  - In this study, we monitored gene expression profiles using cDNA microarrays after
      an acute systemic administration of the high affinity N-methyl-D-aspartate (NMDA)
      uncompetitive antagonist MK-801 (1 mg/kg; 4 h), and the clinically used moderate
      affinity antagonist memantine (25 mg/kg; 4 h) in adult rat brains. From a
      microarray containing 1090 known genes, 13 genes were regulated by both
      treatments of which 12 were upregulated and one was downregulated. In addition,
      28 and 34 genes were regulated (> or = 1.5- or < or = 0.67-fold change) by either
      memantine or MK-801, respectively. Genes commonly regulated by both treatments
      and not previously reported were confirmed by in situ hybridization (ISH) and
      include regenerating liver inhibitory factor-1 (RL/IF-1), GDP-dissociation
      inhibitor 1 (GDI-1), neural visinin Ca2+-binding protein 2 (NVP-2), neuromedin B
      receptor, and Na+/K+ transporting ATPase 2beta. ISH with memantine (5-50 mg/kg)
      revealed regulation of these genes in other cortical and hippocampal regions.
      RL/IF-1 induction occurred at 1 h and returned to basal levels by 8 h, consistent
      with the profile of an immediate early gene. Western blot analysis showed
      increases (approximately 30-65%) in GDI-1 protein present in both cytosolic and
      membrane fractions that were significant in the 84-kDa Rab bound form, suggesting
      that memantine influences Ras-like GTPase function. Genes regulated by a 5 mg/kg
      dose of memantine might be important in its therapeutic effects. These findings
      increase the number of known, differentially altered genes after treatment of
      uncompetitive NMDA receptor antagonists and suggest broader actions of these
      agents than previously realized.

PMID- 14970831
TI  - Amygdala volume reductions in pediatric patients with obsessive-compulsive
      disorder treated with paroxetine: preliminary findings.
AB  - The amygdala is believed to be highly relevant to the pathophysiology of
      obsessive-compulsive disorder (OCD) given its prominent role in fear conditioning
      and because it is an important target of the serotonin reuptake inhibitors
      (SRIs), the pharmacotherapy of choice for OCD. In the present study, we measured
      in vivo volumetric changes in the amygdala in pediatric patients with OCD
      following 16 weeks of monotherapy with the selective SRI, paroxetine
      hydrochloride. Amygdala volumes were computed from contiguous 1.5 mm magnetic
      resonance (MR) images in 11 psychotropic drug-naive patients with OCD prior to
      and then following treatment. Eleven healthy pediatric comparison subjects also
      had baseline and follow-up scans, but none of these subjects received medication.
      Patients demonstrated significant asymmetry of the amygdala (L>R) prior to
      pharmacologic intervention in contrast to healthy comparison subjects who showed
      no asymmetry at the time of their baseline scan. Mixed model analyses using age
      and total brain volume as time varying covariates indicated that left amygdala
      volume decreased significantly in patients following treatment. The reduction in
      left amygdala volume in patients correlated significantly with higher paroxetine
      dosage at the time of the follow-up scan and total cumulative paroxetine exposure
      between the scans. No significant changes in either right or left amygdala volume
      were evident among healthy comparison subjects from the baseline to the follow-up
      scan. These preliminary findings suggest that abnormal asymmetry of the amygdala
      may play a role in the pathogenesis of OCD and that paroxetine treatment may be
      associated with a reduction in amygdala volume.

PMID- 14970832
TI  - Chronic lithium treatment attenuates intracellular calcium mobilization.
AB  - Elevated basal intracellular calcium (Ca(2+)) levels ([Ca(2+)](B)) in B
      lymphoblast cell lines (BLCLs) from bipolar I disorder (BD-I) patients implicate
      altered Ca(2+) homeostasis in this illness. Chronic lithium treatment affects key
      proteins modulating intracellular Ca(2+) signaling. Thus, we sought to determine
      if chronic exposure to therapeutic lithium concentrations also modifies
      intracellular Ca(2+) homeostasis in this surrogate cellular model of signal
      transduction disturbances in BD. BLCLs from BD-I (N=26) and healthy subjects
      (N=17) were regrown from frozen stock and incubated with 0.75 mM lithium or
      vehicle for 24 h (acute) or 7 days (chronic). [Ca(2+)](B), lysophosphatidic acid
      (LPA)-stimulated Ca(2+) mobilization ([Ca(2+)](S)), and thapsigargin-induced
      store-operated Ca(2+) entry (SOCE) were determined using ratiometric fluorometry
      with Fura-2. Compared with vehicle, chronic lithium exposure resulted in
      significantly higher [Ca(2+)](B) (F=8.47; p=0.006) in BLCLs from BD-I and healthy
      subjects. However, peak LPA-stimulated [Ca(2+)](S) and SOCE were significantly
      reduced (F=11.1, p=0.002 and F=8.36, p=0.007, respectively). Acute lithium
      exposure did not significantly affect measured parameters. In summary, the effect
      of chronic lithium to elevate [Ca(2+)](B) in BLCLs while attenuating both
      receptor-stimulated and SOCE components of intracellular Ca(2+) mobilization in
      BLCLs suggests that modulation of intracellular Ca(2+) homeostasis may be
      important to the therapeutic action of lithium.

PMID- 14970833
TI  - Prenatal nicotine exposure alters the response to nicotine administration in
      adolescence: effects on cholinergic systems during exposure and withdrawal.
AB  - Maternal smoking during pregnancy increases the likelihood that the offspring
      will become smokers in adolescence. In the current study, we evaluated effects of
      prenatal and adolescent nicotine exposure in rats to assess whether there is a
      biological basis for this relationship. Pregnant rats were given nicotine or
      vehicle throughout pregnancy and the offspring then again received nicotine or
      vehicle during adolescence (postnatal days PN30-47.5), using a regimen (6
      mg/kg/day by subcutaneous infusion) that produces plasma nicotine levels similar
      to those in smokers. Evaluations were made in the cerebral cortex and midbrain
      during adolescent nicotine administration (PN45) and for up to 1 month after the
      end of treatment. We assessed the magnitude and persistence of nicotinic
      acetylcholine receptor (nAChR) upregulation; in addition, we evaluated
      cholinergic synaptic activity by comparing the effects on choline
      acetyltransferase (ChAT), a constitutive marker for cholinergic nerve terminals,
      with those on hemicholinium-3 (HC-3) binding to the presynaptic choline
      transporter, which is regulated by nerve impulse activity. Prenatal nicotine
      exposure had only minor effects on nAChRs but produced persistent cholinergic
      hypoactivity (reduced HC-3 binding relative to ChAT) throughout adolescence and
      into adulthood (PN75). Adolescent nicotine exposure evoked robust nAChR
      upregulation and also suppressed cholinergic activity. Prenatal nicotine exposure
      reduced the upregulation of nAChRs evoked by adolescent nicotine but worsened the
      cholinergic hypoactivity during withdrawal. Our results indicate that prenatal
      nicotine exposure alters the subsequent response to nicotine in adolescence,
      effects that may contribute to the association between maternal smoking during
      pregnancy and subsequent adolescent smoking in the offspring.

PMID- 14970834
TI  - Reduced immobility in the forced swim test in mice with a targeted deletion of
      the leukemia inhibitory factor (LIF) gene.
AB  - Cytokines are a large and diverse group of polypeptides that are rapidly released
      in response to tissue injury, infection, and inflammation. Besides their effects
      in the periphery, cytokines also affect the central nervous system (CNS). There
      has been increasing interest in the potential role of cytokines in the behavioral
      features of depressive disorders. One cytokine that might be a candidate for a
      role in the etiology of depression is leukemia inhibitory factor (LIF). LIF mRNA
      has been detected in the hypothalamus, hippocampus, amygdala, cerebellum,
      cerebral cortex, and basal forebrain nuclei. The role of LIF in the CNS has not
      been fully elucidated. Based upon the hypothesis that cytokines might have a role
      in depression, the present study characterized the behavior of mice with a
      targeted disruption of the LIF gene (LIF knockouts) in the forced swim test, an
      animal model used to measure depressive-like behavior and the response to
      antidepressants. It was found that LIF knockout mice show reduced immobility in
      the forced swim test, suggesting that LIF might have a potential role in the
      etiology of some forms of depression.

PMID- 14970835
TI  - Total sleep deprivation decreases immobility in the forced-swim test.
AB  - Sleep deprivation can exert antidepressant effects in humans in less than 24 h,
      making it the fastest acting antidepressant treatment. However, it is rarely used
      clinically because the effect disappears once the subject goes back to sleep. An
      understanding of the neurobiological mechanisms underlying the antidepressant
      effect of sleep deprivation should help to develop new rapidly acting
      antidepressant strategies. In the present report, an animal model of depression
      (the forced-swim test) was used to determine whether the effects of total sleep
      deprivation parallel those obtained with antidepressant drugs. Using the disk
      over-water method, rats deprived of sleep for 24 h exhibited increased swimming
      behavior when compared to cage control rats, mimicking the effects of
      serotonergic antidepressants. After 48 h, sleep-deprived rats exhibited increased
      swimming when compared to both cage control and stimulus control rats,
      demonstrating that the effect is due to sleep deprivation per se, and not to
      extraneous factors inherent in the sleep deprivation protocol (such as stress and
      movement). We believe that this paradigm can be used to study the neurobiological
      mechanisms of rapid antidepressant effects induced by sleep deprivation.

PMID- 14970836
TI  - Inhibition of insulin signaling and adipogenesis by rapamycin: effect on
      phosphorylation of p70 S6 kinase vs eIF4E-BP1.
AB  - OBJECTIVE: Insulin-responsive adipogenic signaling molecules include insulin
      receptor substrates (IRS)-1 and -2, phosphoinositide 3-kinase (PI3K), and protein
      kinase B (PKB; also known as Akt). Mammalian target of rapamycin (mTOR) is a PKB
      substrate, and regulates p70 S6 kinase (p70 S6K). Since p70 S6K is an insulin
      responsive kinase downstream of PI3K and PKB, its potential role in adipogenic
      insulin signaling was investigated. DESIGN: We measured the effect of rapamycin,
      a specific inhibitor of mTOR, on insulin-induced 3T3-L1 adipogenesis and on
      insulin-stimulated p70 S6K activation. RESULTS: Rapamycin partially reduced
      differentiation, measured by Oil Red O staining, triacylglycerol accumulation (by
      up to 46%), and peroxisome proliferator-activated receptor gamma protein
      expression (by 50%). In contrast, rapamycin completely inhibited insulin
      stimulated p70 S6K activation, assessed by phosphorylation of p70 S6K and its
      substrate, S6. Expression of a constitutively activated form of p70 S6K did not
      promote 3T3-L1 adipogenesis. The considerable residual differentiation in the
      presence of rapamycin, despite the complete blockade of p70 S6K activation,
      prompted us to measure the phosphorylation of another rapamycin-sensitive
      protein, eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1).
      Insulin-stimulated 4E-BP1 phosphorylation in 3T3-L1 preadipocytes was only
      partially affected by rapamycin, consistent with the differentiation data.
      Phosphorylation of eIF4E itself, an expected consequence of 4E-BP1
      phosphorylation, was also only partially inhibited. CONCLUSION: Our data suggest
      that adipogenic mTOR signaling occurs via the 4E-BP1/eIF4E pathway, rather than
      through p70 S6K.

PMID- 14970837
TI  - Added thermogenic and satiety effects of a mixed nutrient vs a sugar-only
      beverage.
AB  - OBJECTIVE: To examine the effects of a sugar-only (SO) beverage vs one containing
      a mixed-nutrient (MN) composition on energy expenditure and feelings of hunger
      and satiety. HYPOTHESIS: A beverage containing a mixed macronutrient composition
      will lead to greater thermic effect of food and feelings of fullness than an
      isocaloric beverage containing only sugar. RESEARCH METHODS AND PROCEDURES:
      Adults were randomly assigned to receive a 2510 kJ (600 kcal) SO liquid formula
      followed by an isovolumic, isoenergetic, MN liquid formula with an energy
      distribution of 17% protein, 67% carbohydrates as sucrose and corn syrup solids,
      and 16% fat, or vice versa, in a crossover design. The carbohydrate source in the
      two beverages was identical: 1:1 ratio of sucrose and corn syrup solids (25
      dextrose equivalents). The thermic response was calculated as the 7 h deviation
      from resting metabolic rate (RMR). Subjects provided hunger/satiety ratings and
      other related information by visual analog scales at regular intervals throughout
      the study period. RESULTS: In all, 20 subjects completed the protocol; one was
      removed from the thermic effect analysis due to discrepant RMRs. Following
      beverage ingestion, SO and MN liquid meals produced 7 h thermic effects of (X+/
      s.e.m.) 274.1+/-27.6 kJ (65.5+/-6.6 kcal) and 372.0+/-33.9 kJ (88.9+/-8.1 kcal),
      respectively, resulting in a significant (P<0.01) difference between meals
      (Delta=97.9+/-35.1 kJ [23.4+/-8.4 kcal]). Analysis of satiety ratings using area
      under the curve analysis showed greater feelings of satiety (P<0.05) with MN
      compared to SO consumption. Also, subjects felt that they could eat less (P<0.05)
      after consumption of the MN vs SO beverage. DISCUSSION: In comparison to MN
      beverages, SO beverages are associated with a relatively high-energy retention
      without accompanying subjective hunger/fullness compensations, suggesting a basis
      for their role in long-term unintentional weight gain in healthy adults.

PMID- 14970838
TI  - Effects of a multidisciplinary weight loss intervention on body composition in
      obese adolescents.
AB  - OBJECTIVE: To investigate if a multidisciplinary weight loss program in
      adolescents suffering severe obesity allows adequate growth and development and
      avoid lean mass loss. DESIGN: A total of 55 adolescents (33 girls and 22 boys)
      suffering severe obesity were enrolled in an interdisciplinary weight reduction
      program lasting 6-12 months. Progressive submaximal physical activity was
      performed and national dietary allowances for adolescents with low levels of
      physical activity energy were provided. MEASUREMENTS: Total and segmental body
      composition was assessed by means of dual-energy X-ray absorptiometry. RESULTS:
      The mean height significantly increased (P<0.001). The mean body mass index (BMI)
      dropped in boys from 34.5+/-3.2 to 25.5+/-2.3 kg/m(2) and in girls from 38.4+/
      4.1 to 28.4+/-4.1 kg/m(2). Height increased according to the expected pattern
      (P<0.001). Total lean mass (LM) did not vary and was positively correlated to
      pubertal development in both sexes before and after weight loss. Steepest drop in
      fat mass (FM) was observed in the trunk (-63.2+/-10.1% in boys and -51.5+/-11.4%
      in girls). Decrease in BMI and FM was tightly correlated in both sexes. However,
      slopes significantly differed (P<0.0005) so that a decrease of 1 kg/m(2) in BMI
      corresponded to a decrease of 3.92 kg in FM in girls and of 5.44 kg in boys. In
      each sex, FM at baseline and duration of the treatment were the main determinants
      of the decrease in FM. CONCLUSION: During adolescence, despite a major weight
      loss, adequate growth and preservation of LM can be achieved. Weight loss
      kinetics markedly differs between boys and girls. Low-calorie diets are
      unnecessary to achieve a marked reduction of severe obesity during puberty.

PMID- 14970839
TI  - Polyphenolics and fat absorption.
AB  - OBJECTIVES: To elucidate whether the acute consumption of red wine polyphenolic
      compounds regulates lipid and lipoprotein metabolism in dyslipidemic
      postmenopausal women. DESIGN: Eight dyslipidemic postmenopausal women each
      consumed a mixed meal accompanied by either water, dealcoholized red wine or
      alcoholic red wine on three separate visits, in a random order, 2 weeks apart.
      One fasting and six hourly postmeal blood samples were taken and analyzed for
      plasma apolipoprotein B48 (apoB48; specific marker of chylomicrons (CM) and their
      remnants (CMR)); total-, LDL- and HDL-cholesterol; triglycerides (TAG); insulin
      and glucose at each time point. RESULTS: There was a decrease in postprandial
      apoB48 levels after alcoholic and nonalcoholic red wine consumption compared to
      water. CONCLUSION: Red wine attenuates postprandial CM and CMR levels in plasma,
      possibly by delaying the absorption of dietary fat, as suggested by a decrease in
      plasma apoB48 levels. The reduction of postprandial lipoproteins in circulation
      after red wine consumption may partly explain the low cardiovascular mortality
      rates among the French.

PMID- 14970841
TI  - Insulin sensitivity is increased and fat oxidation after a high-fat meal is
      reduced in normal-weight healthy men with strong familial predisposition to
      overweight.
AB  - OBJECTIVE: To evaluate whether postprandial abnormalities of energy expenditure
      and/or lipid oxidation are present in healthy, normal-weight subjects with a
      strong family history of obesity and thus at high risk to become obese. DESIGN:
      Case-control study. SUBJECTS: A total of 16 young healthy men participated in the
      study. Eight subjects had both parents overweight (father's and mother's body
      mass index (BMI) >25 kg/m(2)) and eight had both parents with normal body weight
      (father's and mother's BMI<25 kg/m(2), respectively). The group of subjects with
      overweight parents was similar to that with normal-weight parents (control group)
      in terms of BMI (23.7+/-1.7 vs 22.7+/-1.1 kg/m(2)) (M+/-s.d.) and fat-free body
      mass (FFM) (60.5+/-4.9 vs 58.4+/-2.0 kg), but was slightly older than the control
      group (25.4+/-3.3 vs 22.7+/-2.4 y; P<0.05). MEASUREMENTS: Energy expenditure (EE)
      was measured by indirect calorimetry, and blood samples were taken for the
      evaluation of metabolic variables in the fasting state and every hour for 8 h
      after a standard fat-rich meal (protein 15%, carbohydrate 34%, fat 51%, 4090 kJ).
      RESULTS: : Fasting plasma glucose, cholesterol, HDL-cholesterol, triglyceride,
      free fatty acid (FFA) and leptin concentrations were similar in both groups of
      participants, but subjects with overweight parents has significantly lower plasma
      insulin concentrations (5.11+/-0.51 vs 7.07+/-1.56 microU/ml; P<0.007) and HOMA
      index of insulin resistance (1.1+/-0.1 vs 1.6+/-0.4; P<0.01). Postprandial plasma
      glucose, triglyceride, FFA and leptin concentrations were similar in the two
      groups, whereas insulin levels were significantly lower in the group with both
      parents overweight at 3, 5, 6, 7 and 8 h. Fasting and postprandial EE, and
      fasting lipid and carbohydrate oxidation were similar in both groups. On the
      contrary, postprandial carbohydrate oxidation (incremental area under curve) was
      significantly higher (196.25+/-94.75 vs 75.88+/-74.72 mg/kg FFM x 8 h; P<0.007)
      and that of lipid oxidation lower (90.93+/-80.32 vs 163.68+/-108.22 mg/kg FFM x 8
      h; P<0.05) in the group of subjects with overweight parents. CONCLUSION: Normal
      weight subjects with a strong family history of obesity present a reduced lipid
      oxidation in the postprandial period and a metabolic profile characterized by low
      plasma insulin levels and the HOMA index, which is compatible with increased
      insulin sensitivity. These metabolic characteristics may be considered as early
      predictors of weight gain and are probably genetically determined.

PMID- 14970843
TI  - Genetic analysis of 2299delG and C759F mutations (USH2A) in patients with visual
      and/or auditory impairments.
AB  - The most common mutation in the USH2A gene (Usherin), 2299delG, causes both
      typical Usher (USH) syndrome type II and atypical USH syndrome, two autosomal
      recessive disorders, characterised by moderate to severe sensorineural hearing
      loss and retinitis pigmentosa (RP). Furthermore, the C759F mutation in the USH2A
      gene has been described in 4.5% of patients with nonsyndromic recessive RP. We
      have investigated the presence of the 2299delG and/or the C759F mutations in 191
      unrelated Spanish patients with different syndromic and nonsyndromic retinal
      diseases, or with nonsyndromic hearing impairment. The 2299delG mutation was
      observed in patients with clinical signs of USHII or of atypical USH syndrome,
      whereas the C759F mutation, regardless of being associated with the 2299delG
      mutation or not, was identified in cases with nonsyndromic RP, as well as in
      patients with RP associated with a variability of hearing impairment. The
      comparative analysis of both phenotypic and genotypic data supports the
      hypothesis that sensorineural hearing loss in patients with RP may depend on the
      nature and on the association of the USH2A allele variants present.

PMID- 14970844
TI  - Complete germline deletion of the STK11 gene in a family with Peutz-Jeghers
      syndrome.
AB  - Peutz-Jeghers syndrome (PJS, MIM175200) is an autosomal-dominant inherited
      disorder characterised by multiple gastrointestinal hamartomatous polyps, melanin
      spots of the oral mucosa and digits, and an increased risk for various neoplasms.
      The PJS results from germline alterations of the STK11/LKB1 tumour suppressor
      gene, located on 19p13.3, and encoding a serine/threonine kinase. The detection
      of STK11 germline mutations, in only 50-70% of PJS families, has suggested a
      genetic heterogeneity of the disease. We report the case of a family with typical
      features of PJS, including gastrointestinal hamartomatous, breast cancers and
      melanin spots of the oral mucosa. Quantitative multiplex PCR of short fluorescent
      fragments (QMPSF) of the 19p13 region allowed us to identify an approximately 250
      kb heterozygous deletion removing entirely the STK11 locus. This report, which
      constitutes the first description of a complete germline deletion of STK11, shows
      that the presence of such large genomic deletions should be considered in PJS
      families without detectable point mutations of STK11.

PMID- 14970845
TI  - Polymorphisms in the prion protein gene and in the doppel gene increase
      susceptibility for Creutzfeldt-Jakob disease.
AB  - The prion protein gene (PRNP) plays a central role in the origin of Creutzfeldt
      Jakob disease (CJD), but there is growing interest in other polymorphisms that
      may be involved in CJD. Polymorphisms upstream of PRNP that may modulate the
      prion protein production as well as polymorphisms in the prion-like doppel gene
      (PRND) have been studied, with inconsistent findings. We investigated the role of
      a single-nucleotide polymorphism (SNP 1368) located upstream of PRNP and three
      polymorphisms in PRND (T26M, P56L and T174M) in CJD. The study included a
      population-based sample of 52 patients with sporadic CJD and 250 controls. We
      analysed our data as single markers and haplotypes. Further, we conducted a meta
      analysis on PRND T174M comparing the data of the four studies conducted to date.
      For SNP 1368 and PRNP M129V, we found significant evidence for linkage
      disequilibrium. No evidence was found for a relation of SNP 1368 to CJD
      independent of PRNP M129V. We further found a significant increased prevalence of
      M homozygotes at PRND T174M among sporadic CJD patients, when adjusting the
      analyses for the other genotypes. In the haplotype analyses, the association was
      strongest for persons homozygous for PRNP 129M and PRND 174M (odds ratio 4.35,
      95% confidence interval 1.05-8.09; P=0.04). The meta-analysis on the PRND T174M
      polymorphism did not show a consistent effect across studies, raising the
      question as to whether PRND 174M is causally related to CJD, or whether the PRND
      allele is in linkage disequilibrium with another polymorphism related to CJD.

PMID- 14970846
TI  - Angiotensin I-converting enzyme polymorphisms, ACE level and blood pressure among
      Nigerians, Jamaicans and African-Americans.
AB  - The genes in the renin-angiotensin system are important physiologic candidates in
      studies of the genetic susceptibility to hypertension. Limited information has
      been available in most studies on the extent of variation in the candidate loci
      or the modifying effects of different environmental settings. We consequently
      genotyped 13 polymorphisms at the angiotensin I-converting enzyme (ACE) locus at
      an average distance of 2 kb in 2776 family members from Nigeria, Jamaica and an
      African-American community in the US. Allele and haplotype frequencies were
      similar in the three populations, with modest evidence of European admixture in
      the US. Two markers were consistently associated with ACE level in the three
      samples and the proportion of variance accounted for by ACE8 was similar in the
      three groups. No evidence of consistent association of single markers was noted
      with blood pressure across the three population samples, however. Likewise, in a
      haplotype-based analysis, despite significant associations within each
      population, the findings were not replicated consistently across all three
      samples. We did observe, however, that the overtransmitted haplotypes among
      hypertensives were drawn from a single clade, suggesting that susceptibility may
      cluster in patterns not captured directly by our markers.

PMID- 14970847
TI  - SNPs in cancer research and treatment.
AB  - Genetic variation in the human genome is an emerging resource for studying
      cancer, a complex set of diseases characterised by both environmental and genetic
      contributions. The number of common germ-line variants is great, on the order of
      10-15 million per person, and represents a remarkable opportunity to investigate
      the aetiology, interindividual differences in treatment response and outcomes of
      specific cancers. The study of genetic variation can elucidate critical
      determinants in environmental exposure and cancer, which could have future
      implications for preventive and early intervention strategies. However, we are in
      the initial stages of characterising the tools (i.e., the single-nucleotide
      polymorphism, SNP) to rigorously analyse the genetic contributions to complex
      diseases, such as cancer. If the promise of the genomic era is to be realised, we
      must integrate this information into new strategies for implementation in both
      public health measures and, most importantly, provision of individual cancer
      related care.

PMID- 14970848
TI  - Host genetics and tumour metastasis.
AB  - Metastasis, the spread and growth of tumours at secondary sites, is an extremely
      important clinical event, since a majority of cancer mortality is associated with
      the metastatic tumours, rather than the primary tumour. In spite of the
      importance of metastasis in the clinical setting, the actual process is extremely
      inefficient. Millions of tumour cells can be shed into the vasculature daily;
      yet, few secondary tumours are formed. The classical hypothesis explaining the
      inefficiency was a series of secondary events occurring in the tumour, resulting
      in a small subpopulation of cells capable of completing all of the steps required
      to successfully colonise a distant site. However, recent discoveries
      demonstrating the ability to predict metastatic propensity from gene expression
      profiles in bulk tumour tissue are not consistent with only a small subpopulation
      of cells in the primary tumour acquiring metastatic ability, suggesting that
      metastatic ability might be pre-programmed in tumours by the initiating oncogenic
      mutations. Data supporting both of these seemingly incompatible theories exist.
      Therefore, to reconcile the observed results, additional variables need to be
      added to the model of metastatic inefficiency. One possible variable that might
      explain the discrepancies is genetic background effects. Studies have
      demonstrated that the genetic background on which a tumour arises on can have
      significant affects on the ability of the tumour to metastasise and on gene
      expression profiles. Thus, the observations could be reconciled by combining the
      theories, with genetic background influencing both metastatic efficiency and
      predictive gene expression profiles, upon which, subsequently, metastasis
      promoting mutational and epigenetic events occur. If the genetic background is an
      important determinant of metastatic efficiency, it would have significant
      implications for the clinical prediction and treatment of metastatic disease, as
      well as for the design of potential prevention strategies.

PMID- 14970849
TI  - ALL-1/MLL1, a homologue of Drosophila TRITHORAX, modifies chromatin and is
      directly involved in infant acute leukaemia.
AB  - Rearrangements of the ALL-1/MLL1 gene underlie the majority of infant acute
      leukaemias, as well as of therapy-related leukaemias developing in cancer
      patients treated with inhibitors of topoisomerase II, such as VP16 and
      doxorubicin. The rearrangements fuse ALL-1 to any of >50 partner genes or to
      itself. Here, we describe the unique features of ALL-1-associated leukaemias, and
      recent progress in understanding molecular mechanisms involved in the activity of
      the ALL-1 protein and of its Drosophila homologue TRITHORAX.

PMID- 14970850
TI  - Linking the epigenetic 'language' of covalent histone modifications to cancer.
AB  - Covalent modifications of histones, such as acetylation, methylation, and
      phosphorylation, and other epigenetic modulations of the chromatin, such as
      methylation of DNA and ATP-dependent chromatin reorganisation, can play a major
      part in the multistep process of carcinogenesis, with far-reaching implications
      for human biology and human health. This review focuses on how aberrant covalent
      histone modifications may contribute to the development of a variety of human
      cancers, and discusses the recent findings with regard to potential therapies.

PMID- 14970851
TI  - Hormone replacement therapy after surgery for stage 1 or 2 cutaneous melanoma.
AB  - A total of 206 women were followed for a minimum of 5 years after primary
      melanoma surgery to establish if hormone replacement therapy (HRT) adversely
      affected prognosis. In all, 123 had no HRT and 22 have died of melanoma; 83 had
      HRT for varying periods and one has died of melanoma. After controlling for known
      prognostic factors, we conclude that HRT after melanoma does not adversely affect
      prognosis.

PMID- 14970852
TI  - Interleukin-2 improves tumour response to DNP-modified autologous vaccine for the
      treatment of metastatic malignant melanoma.
AB  - This paper is a report of response rate (RR) and survival of 34 metastatic
      melanoma patients who received a dinitrophenyl (DNP)-modified autologous melanoma
      cell vaccine. In all, 27 patients started the vaccine as a primary treatment for
      metastatic melanoma and seven started it as an adjuvant, with no evidence of
      disease at the time, but had developed new metastases. Interleukin-2 (IL-2) was
      administered in 24 out of the 34 patients: 19 who progressed on vaccine alone and
      five who had the combination from start. Interleukin-2 was administered in the
      intravenous, bolus high-dose regimen (seven patients) or as subcutaneous (s.c.)
      low-dose treatment (17). Overall response for the entire group was 35% (12
      patients out of 34), 12% having a complete response (CR) and 23% a partial
      response (PR). However, only two patients had tumour responses while on the
      vaccine alone, whereas the other 10 demonstrated objective tumour regression
      following the combination with IL-2 (two CR, eight PR), lasting for a median
      duration of 6 months (range 3-50 months). Of the 12 responding patients, 11
      attained strong skin reactivity to the s.c. injection of irradiated, unmodified
      autologous melanoma cells. None of the patients with a negative reactivity
      experienced any tumour response. Patients with positive skin reactions survived
      longer (median survival - 54 months). The results suggest enhanced RRs to the
      combination of IL-2 and autologous melanoma vaccine. Skin reactivity to
      unmodified autologous melanoma cells may be a predictor of response and improved
      survival, and therefore a criterion for further pursuing of immunotherapeutic
      strategies.

PMID- 14970853
TI  - Monitoring temozolomide treatment of low-grade glioma with proton magnetic
      resonance spectroscopy.
AB  - Assessment of low-grade glioma treatment response remains as much of a challenge
      as the treatment itself. Proton magnetic resonance spectroscopy ((1)H-MRS) and
      imaging were incorporated into a study of patients receiving temozolomide therapy
      for low-grade glioma in order to evaluate and monitor tumour metabolite and
      volume changes during treatment. Patients (n=12) received oral temozolomide (200
      mg m(-2) day(-1)) over 5 days on a 28-day cycle for 12 cycles. Response
      assessment included baseline and three-monthly magnetic resonance imaging studies
      (pretreatment, 3, 6, 9 and 12 months) assessing the tumour size. Short (TE (echo
      time)=20 ms) and long (TE=135 ms) echo time single voxel spectroscopy was
      performed in parallel to determine metabolite profiles. The mean tumour volume
      change at the end of treatment was -33% (s.d.=20). The dominant metabolite in
      long echo time spectra was choline. At 12 months, a significant reduction in the
      mean choline signal was observed compared with the pretreatment (P=0.035) and 3
      month scan (P=0.021). The reduction in the tumour choline/water signal paralleled
      tumour volume change and may reflect the therapeutic effect of temozolomide.

PMID- 14970854
TI  - Daily omega-3 fatty acid intake and depression in Japanese patients with newly
      diagnosed lung cancer.
AB  - The aim of the present study was to examine the association between daily omega-3
      fatty acid intake and depression in Japanese cancer patients. Omega-3 fatty acid
      intake in 771 patients with newly diagnosed primary lung cancer was evaluated
      using a food-frequency questionnaire, and the prevalence of depression was
      examined using the cutoff values for the depression subscale included in the
      Hospital Anxiety and Depression Scale. After adjustment for potential confounding
      factors, the odds ratio (OR) for depression among patients in the highest
      quartile of the total eicosapentaenoic acid- (C20:5n-3) and docosapentaenoic acid
      (C22:6n-3)-intake group compared with patients in the lowest quartile was not
      significantly different. On the other hand, the OR among the highest quartile of
      alpha-linolenic acid (C18:3n-3) intake (adjusted OR=0.50, 95% CI: 0.31-0.71, P
      for trend=0.004) and the highest quartile of total omega-3 fatty acid intake
      (adjusted OR=0.55, 95% CI: 0.35-0.88, P for trend=0.022) were significantly
      different. These results suggest that total eicosapentaenoic acid and
      docosapentaenoic acid intake might not be associated with depression in Japanese
      patients with newly diagnosed lung cancer, but that alpha-linolenic acid intake
      and total omega-3 fatty acid intake might be.

PMID- 14970855
TI  - Is treatment with interferon-alpha effective in all patients with metastatic
      renal carcinoma? A new approach to the investigation of interactions.
AB  - The first analysis of the MRC RE01 trial in metastatic renal carcinoma identified
      a 28% reduction in the hazard of death for patients treated with interferon-alpha
      compared with medroxyprogesterone acetate (MPA). No subgroup was identified in
      which treatment with interferon-alpha was more or less effective than MPA. We
      used a new approach based on fractional polynomials to investigate the updated
      data from this trial for the possible interaction of treatment with prognostic
      factors. In the spirit of hypothesis generation, we considered 10 possible
      prognostic variables, of which white cell count (WCC) was found to influence the
      effectiveness of interferon treatment. In patients treated with MPA, there was no
      prognostic effect of WCC, whereas, in patients treated with interferon, the risk
      of dying increased significantly with WCC level. We defined subgroups of patients
      based on WCC levels and estimated a hazard ratio of 0.53 in favour of interferon
      in patients with WCC <6.5 x 10(9), whereas for patients with WCC >10 x 10(9) the
      risk appears to be similar between the treatment groups, or even slightly raised
      in the interferon group. Since our results are derived from flexible statistical
      models, they may be interpreted as a new hypothesis and require validation in
      independent data.

PMID- 14970856
TI  - A phase I and pharmacological study of the matrix metalloproteinase inhibitor BB
      3644 in patients with solid tumours.
AB  - BB-3644 is an oral, broad-spectrum matrix metalloproteinase inhibitor (MMPI)
      structurally related to marimastat and BB-94. It is also >10-fold more active
      than marimastat in inhibiting the processing of cell-bound TNF-alpha. Preclinical
      studies suggested a favourable toxicity profile when compared to marimastat, and
      therefore it was selected for clinical evaluation. Patients with advanced solid
      tumours against which established treatments had failed, or for which no
      satisfactory treatment exists and of good performance status, were eligible.
      Treatment consisted of twice daily (bd) oral BB-3644 for 84 days. The initial
      dose was 5 mg bd, and subsequent cohorts were treated with 10, 20 and 30 mg bd.
      In all, 22 patients were enrolled. The dose-limiting toxicity (DLT) was
      musculoskeletal pain. For 28 days of treatment with BB-3644, 20 mg bd was the
      maximum tolerated dose (MTD), as at 30 mg bd, six of nine patients developed
      significant musculoskeletal toxicity by day 28. Following chronic oral dosing
      (>28 days) with BB-3644, three of five patients treated at 10 mg bd developed
      musculoskeletal DLT by day 84, defining the MTD as 5 mg bd. As dose-limiting
      musculoskeletal toxicity was encountered at doses of BB-3644 unlikely to provide
      an advantage over currently available MMPIs, further evaluation is not
      recommended.

PMID- 14970857
TI  - Photodynamic detection of diseased axillary sentinel lymph node after oral
      application of aminolevulinic acid in patients with breast cancer.
AB  - Benign as well as malignant tumour tissues of the breast demonstrate higher
      fluorescence intensity (FI) than normal breast tissue after application of a
      photosensitiser. As a follow-up study, we evaluated the FI of metastatic sentinel
      lymph nodes and metastatic axillary lymph nodes compared to nonmetastatic
      sentinel and axillary lymph nodes in patients with breast cancer. In all, 11
      patients received 30 mg 5-aminolevulinic acid (ALA) kg(-1) bodyweight orally 3 h
      prior to surgery. The sentinel lymph node was marked with Nanocoll preoperatively
      and with a blue dye intraoperatively. Tumour excision, excision of the sentinel
      lymph node and an axillary lymph node dissection were performed during the same
      surgical session. The operation site was illuminated with blue light (400 nm) to
      obtain macroscopic tissue characterisation of fluorescence. Tissue samples were
      stored protected from light, and analysed using a fluorescence microscope.
      Results were correlated with histopathology. In all, 14 sentinel lymph nodes,
      seven axillary lymph nodes and seven primary tumours were analysed. Metastatic
      sentinel lymph nodes demonstrated a statistically significant higher FI than
      nonmetastatic sentinel lymph nodes (2630 vs 526, P<0.0001). The FI of metastatic
      sentinel lymph nodes, of metastatic axillary lymph nodes and of the primary
      tumour were comparably high, and were statistically significantly higher compared
      to the normal mammary tissue. Intraoperatively, only in a few cases, it was
      possible to recognise the metastatic sentinel lymph node macroscopically with
      blue light. Our study indicates that photodynamic diagnosis with ALA has a
      potential in the diagnosis and detection of the sentinel lymph node in patients
      with breast cancer, and is worth to be further investigated and developed for
      intraoperative photodynamic diagnosis and possibly therapy.

PMID- 14970858
TI  - A phase II study of sequential carboplatin, paclitaxel and topotecan in patients
      with previously untreated advanced ovarian cancer.
AB  - We evaluated the sequential use of carboplatin, paclitaxel and topotecan in
      patients with advanced, previously untreated ovarian cancer. In total, 43
      patients with advanced ovarian cancer and >1 cm residual disease were treated
      with sequential carboplatin (area-under-the-curve (AUC) 5 days 1 and 22),
      paclitaxel (175 mg m(-2) days 43 and 64) and topotecan (1.5 mg m(-2) daily for 5
      days from days 85, 106, 127 and 148). Median age of patients was 61 years. Median
      follow-up was 22.2 months (range 0.76-50.6 months). In all, 34 (79%) patients
      received all eight cycles of treatment and nine (21%) withdrew. Of the 29
      evaluable patients, 19 (66%) responded according to WHO and 30 of 36 (83%)
      patients according to CA125. The best overall response (CA125 and/or WHO) was 77%
      (33 of 43 patients). The response rates to sequential drugs based on >50% fall in
      CA125 were as follows: carboplatin, 77% (30 of 39 patients); paclitaxel, 65% (15
      of 23 patients); topotecan, 38% (five of 13 patients). Two patients responded to
      paclitaxel and one to topotecan after failure to respond to preceding
      chemotherapy. Median survival and time to progression was 22.24 and 10.61 months,
      respectively. This study demonstrates that sequential chemotherapy with just two
      initial courses of carboplatin is a reasonable way to introduce new agents into
      first-line therapy for poor prognostic ovarian cancer patients.

PMID- 14970859
TI  - Polo-like kinase isoform expression is a prognostic factor in ovarian carcinoma.
AB  - The Polo-like kinase (PLK) family comprises three serine/threonine kinases,
      functionally involved in signal transduction pathways essential for the
      accomplishment of mitosis in both normal and malignant cells. Moreover, certain
      PLKs have been functionally linked to cytoskeletal reorganisation. In this study,
      the expression of PLK1 and PLK3 was determined immunohistochemically in tissue
      specimen of normal ovaries (n=9), cystadenomas (n=17), borderline tumours (n=13)
      and ovarian carcinomas (n=77). PLK 1 and PLK3 expression was low in normal
      ovarian surface epithelium and borderline tumours, with moderately higher
      expression levels in cystadenomas. In ovarian carcinomas, 26% of cases were PLK1
      positive and 50.6% of cases were PLK3 positive. A positive correlation of both
      PLK1 and PLK3 expression with indicators of mitotic frequency could be
      established. The overexpression of either isoenzyme had an impact on patient
      prognosis with shortened survival time for patients with tumours positive for
      PLK1 (P=0.02) and PLK3 (P=0.02), but only PLK1 expression remained a prognostic
      factor in multivariate survival analysis (P=0.03). The results of this study, if
      interpreted in the context of recently published functional data, suggest that
      inhibition of PLKs might represent an interesting new targeted approach for
      chemotherapy of epithelial ovarian cancer. Furthermore, this study suggests that
      PLK1 is a novel independent prognostic marker in ovarian carcinomas.

PMID- 14970860
TI  - Tumour-derived TGF-beta1 modulates myofibroblast differentiation and promotes
      HGF/SF-dependent invasion of squamous carcinoma cells.
AB  - The development of an altered stromal microenvironment is a common feature of
      many tumours including squamous cell carcinoma (SCC), and there is increasing
      evidence that these changes in the stroma, which include increased expression of
      proteases and cytokines, may actually promote tumour progression. A common
      finding is that stromal fibroblasts become 'activated' myofibroblasts, expressing
      smooth muscle actin and secreting cytokines, proteases and matrix proteins. We
      show that myofibroblasts are commonly found in the stroma of oral SCC and are
      often concentrated at the invasive margin of the tumour. Using oral SCC cells and
      primary oral fibroblasts, we demonstrate that tumour cells directly induce a
      myofibroblastic phenotype, and that this transdifferentiation is dependent on SCC
      derived TGF-beta1. In turn, myofibroblasts secrete significantly higher levels of
      hepatocyte growth factor/scatter factor compared with fibroblast controls, and
      this cytokine promotes SCC invasion through Matrigel, a mixture of basement
      membrane proteins. This is the first time that this double paracrine mechanism
      has been demonstrated between squamous carcinoma cells and fibroblasts, and
      emphasises that cancer invasion can be promoted indirectly by the release of
      tumour-induced host factors from stroma.

PMID- 14970861
TI  - Overexpression of squamous cell carcinoma antigen variants in hepatocellular
      carcinoma.
AB  - Pathogenetic mechanisms of hepatocellular carcinoma (HCC) are still unclear and
      new tools for diagnostic and therapeutic purposes are ongoing. We have assessed
      whether squamous cell carcinoma antigen (SCCA), a serpin overexpressed in
      neoplastic cells of epithelial origin, is also expressed in liver cancer.
      Squamous cell carcinoma antigen was evaluated by immunohistochemistry in 65 HCCs
      of different aetiology and in 20 normal livers. Proliferative activity was
      assessed using MIB-1 antibody. In 18 surgical samples, tumour and nontumour liver
      tissue was available for SCCA cDNA amplification and sequencing. Squamous cell
      carcinoma antigen was detected in 55 out of 65 (85%) tumour specimens, but in
      none of the 20 controls. In the majority of the cases, the positive signal was
      found in the cytoplasm of more than 50% of the hepatocytes. Low or undetectable
      SCCA (score<or=1) was associated to lower MIB-1 labelling index, compared to
      cases with SCCA score >or=2 (mean+/-s.d.: 2%+/-2.4 vs 7.5%+/-10.3, P<0.05).
      Squamous cell carcinoma antigen mRNA could be directly sequenced in 14 out of 18
      liver tumours but in none of the corresponding nontumour samples. From sequence
      alignment, a novel SCCA1 variant (G(351) to A) was identified in five cases,
      while SCCA1 was revealed in six cases and SCCA2 in three cases. In conclusion,
      SCCA variants are overexpressed in HCC, independently of tumour aetiology. A
      novel SCCA1 variant has been identified in one third of liver tumours.

PMID- 14970862
TI  - Demethylation of MAGE promoters during gastric cancer progression.
AB  - Melanoma antigen (MAGE)-encoding genes are expressed in various tumour types via
      demethylation of their promoter CpG islands, which are silent in all non
      neoplastic tissues except for the testis and placenta. The clinicopathological
      significance of demethylation of MAGE genes in gastric carcinoma is not known. We
      investigated the promoter methylation status of MAGE-A1 and -A3 in 10 gastric
      cancer cell lines and in surgical specimens from 84 gastric cancer patients by
      methylation-specific PCR (MSP). Expression of MAGE-A1 and -A3 in the 10 gastric
      cancer cell lines was also investigated by RT-PCR. Any correlation between the
      methylation status of the MAGE promoters and clinicopathological characteristics
      of the gastric cancer patients was then assessed. Eight of the 10 gastric cancer
      cell lines showed demethylation of both MAGE-A1 and -A3, and the remaining two
      cell lines did either of MAGE-A1 or -A3. Expression of MAGE-A1 and -A3 was
      confirmed in seven and nine of the 10 gastric cancer cell lines, respectively.
      The MAGE-A1 and -A3 promoters were demethylated in 29% (25 out of 84) and 66% (56
      out of 84) of the gastric tumour specimens, respectively. Demethylation of both
      MAGE-A1 and -A3 promoters (n=22) was found more frequently in gastric cancer
      patients in advanced clinical stages (P=0.0035), and these patients also
      exhibited a higher incidence of lymph node metastasis (P=0.0007) compared to
      those patients without demethylation (n=25). Furthermore, demethylation patients
      tended to have a worse prognosis, although this difference was not statistically
      significant (P=0.183). Demethylation of MAGE-A1 and -A3 occurs during progressive
      stages of gastric cancer, and may be associated with aggressive biological
      behaviour of gastric cancer.

PMID- 14970863
TI  - Inactivation of class II transactivator by DNA methylation and histone
      deacetylation associated with absence of HLA-DR induction by interferon-gamma in
      haematopoietic tumour cells.
AB  - By presenting immunogenic peptides at the cell surface, major histocompatibility
      complex (MHC) class II molecules play a key role in the control of adaptive
      immune responses. Whether expressed constitutively or induced by interferon
      gamma, expression of MHC class II molecules is regulated via coactivator class II
      transactivator (CIITA); moreover, suppression of their expression is one
      mechanism by which cancer cells escape host immunity. In this study, we surveyed
      the relationship between the expression of one MHC class II antigen, HLA-DR, and
      its coactivators in a group of haematopoietic cell lines, and explored the role
      of the aberrant DNA methylation in silencing HLA-DR expression. Among 26 cell
      lines studied, HLA-DR expression was lost from eight T-cell and two myeloid
      leukaemia cell lines, and this loss was closely associated with suppression of
      CIITA-PIV expression. Notably, nine of the 10 cell lines that lost CIITA-PIV
      expression showed methylation of the gene's 5' CpG island. Thus, DNA methylation
      is believed to inhibit the expression of MHC class II molecules in haematopoietic
      tumour cells by silencing its coactivator, CIITA-PIV. Furthermore, methylation of
      CIITA-PIV was detected in seven of 32 primary acute myeloid leukaemia specimens,
      indicating that epigenetic alteration is not a cell line-specific phenomenon.
      Collectively, these data suggest that, by suppressing expression of MHC class II
      molecules, epigenetic inactivation of CIITA provides a survival advantage to a
      subset of haematopoietic tumours.

PMID- 14970864
TI  - Tumour necrosis factor and PI3-kinase control oestrogen receptor alpha protein
      level and its transrepression function.
AB  - Oestrogen receptor alpha (ERalpha) is an oestrogen-activated transcription
      factor, which regulates proliferation and differentiation of mammary epithelial
      cells by activating or repressing gene expression. ERalpha is a critical
      prognostic indicator and a therapeutic target for breast cancer. Patients with
      tumours that express higher level of ERalpha have better prognosis than patients
      with tumours that are ERalpha negative or express lower level of ERalpha. Better
      prognosis in ERalpha-positive patients is believed to be due to repression of
      proinvasive gene expression by ERalpha. Oestrogen receptor alpha represses gene
      expression by transrepressing the activity of the transcription factors such as
      nuclear factor-kappaB or by inducing the expression of transcriptional
      suppressors such as MTA3. In this report, we show that ERalpha transrepresses the
      expression of the proinvasive gene interleukin 6 (IL-6) in ERalpha-negative MDA
      MB-231 breast cancer cells stably overexpressing ERalpha. Using these cells as
      well as ERalpha-positive MCF-7 and ZR-75-1 cells, we show that tumour necrosis
      factor alpha (TNFalpha) and the phosphatidylinositol-3-kinase (PI3-kinase)
      modulate transrepression function of ERalpha by reducing its stability. From
      these results, we propose that TNFalpha expression or PI3-kinase activation lead
      to reduced levels of ERalpha protein in cancer cells and corresponding loss of
      transrepression function and acquisition of an invasive phenotype.

PMID- 14970865
TI  - Identification and characterisation of constitutional chromosome abnormalities
      using arrays of bacterial artificial chromosomes.
AB  - Constitutional chromosome deletions and duplications frequently predispose to the
      development of a wide variety of cancers. We have developed a microarray of 6000
      bacterial artificial chromosomes for array-based comparative genomic
      hybridisation, which provides an average resolution of 750 kb across the human
      genome. Using these arrays, subtle gains and losses of chromosome regions can be
      detected in constitutional cells, following a single overnight hybridisation. In
      this report, we demonstrate the efficiency of this procedure in identifying
      constitutional deletions and duplications associated with predisposition to
      retinoblastoma, Wilms tumour and Beckwith-Wiedemann syndrome.

PMID- 14970866
TI  - Cellular responses to ionising radiation of AT heterozygotes: differences between
      missense and truncating mutation carriers.
AB  - It has been estimated that approximately 1% of the general population are ataxia
      telangiectasia (AT) mutated (ATM) heterozygotes. The ATM protein plays a central
      role in DNA-damage response pathways; however, the functional consequences of the
      presence of either heterozygous truncating or missense mutations on ATM
      expression and the ionising radiation (IR)-induced cellular phenotype remain to
      be fully determined. To investigate this relationship, the ATM mRNA and protein
      levels and several cellular end points were characterised in 14 AT heterozygote
      (AT het) lymphoblastoid cell lines, compared to normal and AT homozygote lines.
      The AT het cell lines displayed a wide range of IR-induced responses: despite
      lower average levels of ATM mRNA and protein expression compared to normal cells,
      13 out of 14 were capable of phosphorylating the ATM substrates p53-ser15 and
      Chk2, leading to a normal cell cycle progression after irradiation. However, cell
      survival was lower than in the normal cell lines. The presence of a missense
      compared to a truncating mutation was associated with lower cell survival after
      exposure to 2 Gy irradiation (P=0.005), and a higher level of ATM mRNA expression
      (P=0.047). Our results underline the difficulty in establishing a reliable test
      for determining ATM heterozygosity.

PMID- 14970867
TI  - Promoter hypermethylation of MGMT, CDH1, RAR-beta and SYK tumour suppressor genes
      in granulosa cell tumours (GCTs) of ovarian origin.
AB  - Ovarian carcinoma (OC) is a leading cause of death among women throughout the
      world. A number of cancer-associated genes have been shown to be inactivated by
      hypermethylation of CpG islands during tumorigenesis. We tested the hypothesis
      that methylation status of MGMT, CDH1, RAR-beta and SYK could be important in the
      ovarian tumorigenic process and can lead to the gene(s) inactivation. Therefore,
      we assessed the promoter hypermethylation of MGMT, CDH1, RAR-beta and SYK in 43
      ovarian granulosa cell tumours (GCTs) (adult type) using methylation-specific
      PCR. These tumours are relatively rare, accounting for approximately 3% of all
      ovarian cancers. Hypermethylation of MGMT (in 14 tumours), CDH1 (in nine
      tumours), RAR-beta (in eight tumours) and SYK (in seven tumours) have been found.
      Selective loss of RAR-beta and RAR-beta2 mRNA has been found in seven patients,
      while that of MGMT and SYK in three patients who also show aberrant methylation
      in promoter region of RAR-beta in addition to MGMT, SYK and CDH1 genes. Promoter
      CpG hypermethylation may be an alternative to mutation(s) to inactivate tumour
      suppressor genes such as MGMT, CDH1, RAR-beta and SYK, and this can also be an
      early event in the pathogenesis of OCs. Moreover, hypermethylation of the MGMT
      and CDH1, MGMT and RAR-beta and CDH1 and RAR-beta promoters occurred concordantly
      (P< 0.001, 0.0421 and 0.0005 respectively; Fischer's exact test). In addition to
      this, monosomy 22 and trisomy 14 have also been found in 10 tumours. It is clear
      from the results that hypermethylation of the promoter region of these tumour
      suppressor genes, monosomy 22 and trisomy 14, may be critical steps in the
      tumorigenesis, which consequently play a permissive role for tumour
      aggressiveness. All these events might play an important role in the early
      clinical diagnosis of the disease. Our results, therefore, suggest a potential
      role for epigenetic modification of these critical tumour suppressor genes in
      pathways relevant to the transformation and differentiation of rare type of
      ovarian cancer (GCTs).

PMID- 14970868
TI  - Genetic testing among high-risk individuals in families with hereditary
      nonpolyposis colorectal cancer.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is frequently associated with
      constitutional mutations in a class of genes involved in DNA mismatch repair. We
      identified 32 kindreds, with germline mutations in one of three genes hMSH2,
      hMLH1 or hMSH6. In this study, we purposed to evaluate how many high-risk
      individuals in each family underwent genetic testing: moreover, we assessed how
      many mutation-positive unaffected individuals accepted colonoscopic surveillance
      and the main findings of the recommended follow-up. Families were identified
      through a population-based registry, or referred from other centres. Members of
      the families were invited for an education session with two members of the staff.
      When a kindred was consistent with HNPCC, neoplastic tissues were examined for
      microsatellite instability (MSI) and immunohistochemical expression of MSH2, MLH1
      and MSH6 proteins. Moreover, constitutional mutations were searched by SSCP or
      direct sequencing of the whole genomic region. Of the 164 subjects assessed by
      genetic testing, 89 were gene carriers (66 affected - that is, with HNPCC-related
      cancer diagnosis - and 23 unaffected) and 75 tested negative. Among the 23
      unaffected gene carriers, 18 (78.3%) underwent colonoscopy and four declined. On
      a total of 292 first degree at risk of cancer, 194 (66.4%) did not undergo
      genetic testing. The main reasons for this were: (a) difficulty to reach family
      members at risk, (b) lack of collaboration, (c) lack of interest in preventive
      medicine or 'fatalistic' attitude towards cancer occurrence. The number of
      colorectal lesions detected at endoscopy in gene carriers was significantly
      (P<0.01) higher than in controls (noncarriers). We conclude that a large fraction
      of high-risk individuals in mutation-positive HNPCC families does not undergo
      genetic testing, despite the benefits of molecular screening and endoscopic
      surveillance. This clearly indicates that there are still barriers to genetic
      testing in HNPCC, and that we are unable to provide adequate protection against
      cancer development in these families.

PMID- 14970869
TI  - The CHEK2(*)1100delC mutation has no major contribution in oesophageal
      carcinogenesis.
AB  - In response to DNA damage, the cell cycle checkpoint kinase 2 (CHEK2) may
      phosphorylate p53, Cdc25A and Cdc25C, and regulate BRCA1 function, leading to
      cell cycle arrest and DNA repair. The truncating germline mutation
      CHEK2(*)1100delC abrogates kinase activity and confers low-penetrance
      susceptibility to breast cancer. We found CHEK2(*)1100delC in 0.5% of 190
      oesophageal squamous cell carcinomas and in 1.5% of 196 oesophageal
      adenocarcinomas. In addition, we observed the mutation in 3.0% of 99 Barrett's
      metaplasias and 1.5% of 66 dysplastic Barrett's epithelia, both known precursor
      lesions of oesophageal adenocarcinoma. Since CHEK2(*)1100delC mutation
      frequencies did not significantly differ among oesophageal squamous cell
      carcinomas, adenocarcinomas and (dysplastic) Barrett's epithelia, as compared to
      healthy individuals, we conclude that the CHEK2(*)1100delC mutation has no major
      contribution in oesophageal carcinogenesis.

PMID- 14970870
TI  - Frequent loss of the AXIN1 locus but absence of AXIN1 gene mutations in
      adenocarcinomas of the gastro-oesophageal junction with nuclear beta-catenin
      expression.
AB  - Up to 60% of gastro-oesophageal junction (GEJ) adenocarcinomas show nuclear beta
      catenin expression, pointing to activated T-cell factor (TCF)/beta-catenin-driven
      gene transcription. We demonstrate in five human GEJ adenocarcinoma cell lines
      that nuclear beta-catenin expression indeed correlates with enhanced TCF-mediated
      transcription of a reporter gene. In several tumour types, TCF/beta-catenin
      activation is caused by mutations in either adenomatous polyposis coli (APC),
      beta-catenin exon 3, AXIN1, AXIN2 or beta-transducin repeat-containing protein
      (beta-TrCP). In GEJ adenocarcinomas, very few APC and beta-catenin mutations have
      been found. Therefore, the mechanism of Wnt pathway activation remains unclear.
      In the present study, we did not find AXIN1 gene mutations in 17 GEJ tumours with
      nuclear beta-catenin expression (without beta-catenin exon 3 mutations). Six
      intragenic single nucleotide polymorphisms (SNPs) were identified. One of these,
      the AXIN1 gene T1942C SNP, has a frequency of 21% but is only very recently
      described despite numerous AXIN1 gene mutational studies. We provide evidence why
      this SNP was missed in single strand conformation polymorphism analyses. The
      AXIN1 gene G2063A variation was previously described as a gene mutation but we
      demonstrate that this is a polymorphism. With these six SNPs loss of
      heterozygosity (LOH) was found in 11 of 15 (73%) informative tumours. To
      investigate a possible AXIN1 gene dosage effect in GEJ tumours expressing nuclear
      beta-catenin, AXIN1 locus LOH was determined in 20 tumours expressing membranous
      and no nuclear beta-catenin. LOH was found in 10 of 13 (77%) informative cases.
      AXIN1 protein immunohistochemistry revealed cytoplasmic expression in all tumours
      irrespective of the presence of AXIN1 locus LOH. These data indicate that nuclear
      beta-catenin expression is indicative for activated Wnt signalling and that
      neither AXIN1 gene mutations nor AXIN1 locus LOH are involved in Wnt pathway
      activation in GEJ adenocarcinomas.

PMID- 14970871
TI  - Chromosomal analysis of non-small-cell lung cancer by multicolour fluorescent in
      situ hybridisation.
AB  - The cytogenetic abnormalities in non-small-cell lung cancer remain elusive due
      primarily to the difficulty in obtaining metaphase spreads from solid tumours. We
      have used the molecular cytogenetic techniques of multicolour fluorescent in situ
      hybridisation (M-FISH) and comparative genomic hybridisation (CGH) to analyse
      four primary non-small-cell lung cancer samples and two established cell lines
      (COR-L23 and COR-L105) in order to identify common chromosomal aberrations. CGH
      revealed regions on 5p, 3q, 8q, 11q, 2q, 12p and 12q to be commonly over
      represented and regions on 9p, 3p, 6q, 17p, 22q, 8p, 10p, 10q and 19p to be
      commonly under-represented. M-FISH revealed numerous complex chromosomal
      rearrangements. Translocations between chromosomes 5 and 14, 5 and 11 and 1 and 6
      were observed in three of the six samples, with a further 14 translocations being
      observed in two samples each. Loss of the Y chromosome and gains of chromosomes
      20 and 5p were also frequent. Chromosomes 4, 5, 8, 11, 12 and 19 were most
      frequently involved in interchromosomal translocations. Further investigation of
      the recurrent aberrations will be necessary to identify the specific breakpoints
      involved and any role they may have in the aetiology, diagnosis and prognosis of
      non-small-cell lung cancer.

PMID- 14970872
TI  - Relationship between tumour endothelial cell apoptosis and tumour blood flow
      shutdown following treatment with the antivascular agent DMXAA in mice.
AB  - 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) is currently undergoing clinical
      evaluation as an antivascular agent for the treatment of cancer. We have
      previously demonstrated that DMXAA induces apoptosis of vascular endothelial
      cells in murine tumour sections and in a breast carcinoma biopsy from one patient
      in a Phase I trial. We wished to determine the tissue selectivity of this effect
      and its relationship to induced blood flow changes. Mice with Colon 38 tumours
      were treated with DMXAA and tissues were examined for apoptosis by TdT-mediated
      dUTP nick-end labelling (TUNEL). Hoechst 33342 was used to stain functional
      vessels, with the loss of stained vessels used as a measure of tumour vascular
      collapse. Treatment with DMXAA at 25 mg kg(-1), its maximum tolerated dose (MTD),
      showed, after 3 h, a 12-fold increase in TUNEL staining of tumour vascular
      endothelial cells. In contrast, tissue from the heart, brain, liver and spleen
      showed no increase. Induction of apoptosis in tumour tissue was both dose
      dependent, observable at doses as low as 5 mg kg(-1), and time-dependent.
      Apoptosis was significantly lower in Colon 38 tumours of mice, with a targeted
      disruption in the TNF gene (TNF(-/-)), or in the TNF receptor 1 gene (TNFR(-/-)),
      as compared with that in wild-type mice. Increasing the DMXAA dose to 50 mg kg(
      1) in these knockout mice raised tumour apoptosis to a level comparable to that
      induced in wild-type mice given DMXAA at the MTD. For all the data, a significant
      correlation (r=0.94; P<0.001) was found between logarithmic percentage apoptosis
      induction and the logarithmic density of Hoechst-stained vessels. These results
      suggest that blood flow inhibition caused by DMXAA is tumour tissue-specific and
      is a consequence of induction of apoptosis in tumour vascular endothelial cells.

PMID- 14970873
TI  - CYP3A4, CYP2C9 and CYP2B6 expression and ifosfamide turnover in breast cancer
      tissue microsomes.
AB  - Ifosfamide is a prodrug that requires bioactivation by cytochrome P450 for
      antitumour activity. Up to now, little is known, to what extent in addition to
      the liver the ifosfamide metabolism may occur intratumorally. For this purpose,
      we investigated the expression of CYP3A4, CYP2C9 and CYP2B6 in breast cancer
      tissue using Western Blotting. Ifosfamide turnover was determined by detection of
      metabolites of the ifosfamide 4-hydroxylation and N-dechloroethylation in tumour
      microsomal incubations using HPLC/UV and LC/MS. The results demonstrate that all
      mammary tumours (n=11) reveal CYP3A4 expression; contents varied from 0.5 to 63
      pmol mg(protein)(-1). CYP2C9 (n=9) was present in all tested breast tumour
      samples, too, while CYP2B6 (n=10) protein could not be detected. All measured
      breast cancer microsomes (n=4) showed an ifosfamide N-dechloroethylation capacity
      in the range from 0.04 to 0.21 pmol min(-1) mg(protein)(-1), while metabolites of
      the 4-hydroxylation could not be determined. In conclusion, the detected presence
      of CYP3A4 and CYP2C9 in breast tumours offers the possibility of intratumoral
      turnover of ifosfamide. For the first time in the literature, we could
      demonstrate a turnover of ifosfamide by microsomal preparations from human breast
      cancer tissue. A calculated modulation of intratumoral ifosfamide turnover could
      considerably influence its therapeutic efficiency.

PMID- 14970874
TI  - N-hexanoyl-sphingomyelin potentiates in vitro doxorubicin cytotoxicity by
      enhancing its cellular influx.
AB  - Anticancer drugs generally have intracellular targets, implicating transport over
      the plasma membrane. For amphiphilic agents, such as the anthracycline
      doxorubicin, this occurs by passive diffusion. We investigated whether exogenous
      membrane-permeable lipid analogues improve this drug influx. Combinations of
      drugs and lipid analogues were coadministered to cultured endothelial cells and
      various tumour cell lines, and subsequent drug accumulation in cells was
      quantified. We identified N-hexanoyl-sphingomyelin (SM) as a potent enhancer of
      drug uptake. Low micromolar amounts of this short-chain sphingolipid, being not
      toxic itself, enhanced the uptake of doxorubicin up to 300% and decreased its
      EC(50) toxicity values seven- to 14-fold. N-hexanoyl SM acts at the level of the
      plasma membrane, but was found not incorporated in (isolated) lipid rafts, and
      artificial disruption or elimination of raft constituents did not affect its drug
      uptake-enhancing effect. Further, any mechanistic role of the endocytic
      machinery, membrane leakage or ABC-transporter-mediated efflux could be excluded.
      Finally, a correlation was established between the degree of drug lipophilicity,
      as defined by partitioning in a two-phase octanol-water system, and the
      susceptibility of the drug towards the uptake-enhancing effect of the
      sphingolipid. A clear optimum was found for amphiphilic drugs, such as
      doxorubicin, epirubicin and topotecan, indicating that N-hexanoyl-SM might act by
      modulating the average degree of plasma membrane lipophilicity, in turn
      facilitating transbilayer drug diffusion. The concept of short-chain
      sphingolipids as amphiphilic drug potentiators provides novel opportunities for
      improving drug delivery technologies.

PMID- 14970875
TI  - Forced expression of heat-shock protein 70 increases the secretion of Hsp70 and
      provides protection against tumour growth.
AB  - Although heat-shock protein 70 (Hsp70) has been considered an intracellular
      protein, we report that Hsp70 is secreted under normal cell culture conditions by
      human prostate cell lines, LAPC-4, PC-3, CWR-22, RWPE-1 and -2, LNCaP, and TRAMP
      (transgenic adenocarcinoma mouse prostate)-C2. We found that the secretion can be
      enhanced by transfection with cDNA encoding for Hsp70. To verify that the Hsp70
      detected in the supernatant was not secondary to cell leakage, C2 cells were
      cotransfected with cytoplasmic Renilla luciferase as a reporter. High levels of
      activities were noted in the cell extracts, while no enzyme activities were
      detected in the supernatants. To verify that forced oversecretion of Hsp70 could
      protect against tumour growth, mice were injected with C2 cells transfected with
      an Hsp70 DNA construct and challenged with live tumour cells. Mice injected with
      cells transfected with the Hsp70 DNA construct demonstrated a significantly
      decreased rate of tumour growth compared to those injected with empty vector. In
      addition, a difference in survival rate as defined by a surrogate end point was
      noted between the two groups. In a second experiment, we developed a cell line
      that stably overexpressed Hsp70. Mice injected with these cells also demonstrated
      a significant decrease in tumour growth and significantly increased survival.

PMID- 14970877
TI  - Is CD1a involved in antitumour immune responses during carcinogenesis?

PMID- 14970876
TI  - Pharmacokinetics and efficacy of 2-methoxyoestradiol and 2-methoxyoestradiol-bis
      sulphamate in vivo in rodents.
AB  - 2-Methoxyoestradiol (2-MeOE2) is an endogenous oestrogen metabolite that inhibits
      the proliferation of cancer cells in vitro, and it is also antiangiogenic. In
      vivo 2-MeOE2, when administered at relatively high doses, inhibits the growth of
      tumours derived from breast cancer cells, sarcomas and melanomas. Sulphamoylated
      derivatives of 2-MeOE2 are more potent inhibitors of in vitro breast cancer cell
      growth than 2-MeOE2. In the present study, we have compared the pharmacokinetic
      profiles and metabolism of 2-MeOE2 and its sulphamoylated derivative, 2
      methoxyoestradiol-bis-sulphamate (2-MeOE2bisMATE), in adult female rats. Their
      ability to inhibit tumour growth was compared in nude mice bearing xenografts
      derived from MDA-MB-435 (oestrogen receptor negative) melanoma cancer cells.
      After a single oral 10 mg kg(-1) dose of 2-MeOE2bisMATE, significant
      concentrations of this compound were still detectable at 24 h. In contrast, no 2
      MeOE2 or metabolites were detected in plasma at any time after a 10 mg kg(-1)
      oral dose. Thus, the bioavailability of 2-MeOE2 is very low, whereas for 2
      MeOE2bisMATE it was 85%. No significant metabolites of 2-MeOE2bisMATE were
      detected in plasma after oral or intravenous dosing, showing that this drug is
      resistant to metabolism. In the tumour efficacy model, oral administration of 2
      MeOE2bisMATE, at 20 mg kg(-1) day(-1) daily for 28 days, almost completely
      inhibited tumour growth. Inhibition of tumour growth was maintained for a further
      28 days after the cessation of dosing. At this dose level, 2-MeOE2 did not
      inhibit tumour growth. The resistance to metabolism shown by 2-MeOE2bisMATE and
      its ability to inhibit tumour growth in vivo suggest that this compound should
      have considerable potential for development as a novel anticancer drug.

PMID- 14970879
TI  - [Chemical constituents from Chinese marine sponge Cinachyrella australiensis].
AB  - OBJECTIVE: To investigate the secondary metabolites from Chinese marine Sponge
      Cinachyrella australiensis. METHODS: Column chromatography techniques including
      HPLC were used for the separation and purification of the compounds, and
      extensive spectral analyses including various 2D NMR spectra were employed for
      structure elucidation. RESULTS: Nineteen compounds were obtained,including 2
      methyoxy-6,12,15-trien-8-yne-octadecanoic acid (1), 2-benzenedicarboxylic acid
      dibutyl ester(2), 1,2-benzenedicarboxylic acid bis(2-ethylhexyl)ester(3), (-)
      (3S)-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid(4), L-Tryptophan (5), p
      hydroxylbenzaldehyde (6), p-hydroxyl-benzylethanol(7), p-hydroxyl-benzyl
      propanol(8), cholesta-4-en-3-ol(9), 2-methyl-6-amino-9-(2-deoxy-beta-D-
      ribofuranosyl-purine(10), 2'-Deoxyadenosine (11), 6-amino-9-beta-D-ribofuranosyl
      9H-purine (12),uracil(13), thymine(14), thymidine(15), 1-(2-deoxy-beta-D
      Ribofuranosyl) uracil(16), 1-ethyl-alpha-(2-deoxy)-beta-D
      ribofuranos(17),isolumichrome(18),and zarzissine(19). CONCLUSION: Compounds 1 and
      18 are new natural products,and compounds 2 to 17 as well as 19 are isolated from
      this species for the first time.

PMID- 14970880
TI  - [A new triterpenoid saponin julibroside J24 from the stem bark of Albiza
      julibrissin].
AB  - OBJECTIVE: To separate chemical and active constituents from the stem bark of
      Albiza julibrissin. METHODS: Chromatography and spectral methods were used.
      RESULTS: 3-O-beta-D-xylopyranosyl-(1-->2)-alpha-L-arabinopyranosyl-(1-->6)-beta-D
      glucopyranosyl-21-O-[(6S)-2-trans-2-hydroxymethyl-6-methyl-6-O-[3-O-(6S)-2-trans
      2-hydroxymethyl-6-methyl-6-hydroxy-2,7-octadienoyl)-beta-D-xylopyranosyl]-2,7
      octadienoyl]-acacic acid-28-O-beta-D-glucopyranosyl-(1-->3)-[alpha-L
      arabinofuranosyl-(1-->4)]-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl
      ester (1) was separated and identified. CONCLUSION: Compound 1 is a new saponin
      named as Julibroside J(24).

PMID- 14970881
TI  - [Studies on the chemical constituents from Potentilla multifida L].
AB  - OBJECTIVE: To study the chemical constituents of Potentilla multifida L. METHODS:
      Chemical constituents were isolated by the repeated silica gel chromatography and
      Sephadex LH-20, and their structures were identified by the spectral analysis.
      RESULTS: Five compounds were obtained as follows: 3beta,24-dihydroxyl-urs-12-ene
      (1), ursolic acid (2), euscaphic acid (3), tormentic acid (4), and epihedaragenin
      (5). CONCLUSION: Five compounds were isolated from this plant for the first time.
      Compounds 1 and 5 were isolated from this genus for the first time. Compound 1
      was a new natural product.

PMID- 14970882
TI  - [Studies on the chemical structure of polysaccharide CDP-4 isolated from
      Cistanche deserticola].
AB  - OBJECTIVE: To study the chemical structure of polysaccharide CDP-4 isolated from
      Cistanche deserticola Y.C.Ma. METHODS: The chemical properties of CDP-4 were
      determined by using chemical method and spectrocospic method. RESULTS: CDP-4 was
      composed of glucosyl group, with the ratio 1,4-linkage glcp:1,6-linkage
      glcp=3:1,and its mean molecular weight 1.4 x 10(4). By means of methlylation
      analysis, complete acid hydrolysis analysis, NMR spectrum, the linkages and
      sequence information of CDP-4 were obtained. CONCLUSION: CDP-4 is a new linear
      glucan.

PMID- 14970883
TI  - [Caffeic acid (CA) protects cerebellar granule neurons (CGNs) from apoptosis
      induced by neurotoxin 1-methyl-4-phenylpyridnium (MPP+)].
AB  - OBJECTIVE: To assess the effects of caffeic acid (CA) on MPP(+)-induced
      cerebellar granule neurons (CGNs) apoptosis. METHODS: CGNs were pretreated with
      caffeic acid at 55, 110 and 220 micromol/L for 6 h, then treated with 100
      micromol/L MPP(+) for 24 h (concentration-effect relationship). In addition CGNs
      were pretreated with caffeic acid at 110 micromol/L for 0 h, 6 h, 12 h, and 24 h,
      respectively, then treated with 100 micromol/L MPP(+) for 24 h (time-response
      relationship). Besides, after treatment with MPP(+) for 24 h, CGNs were incubated
      with caffeic acid at 55, 110 and 220 micromol/L, respectively. Cell viability was
      determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay and caspase-3 activity was assayed by caspase-3 fluorometric assay kit.
      RESULTS: MTT assay revealed that caffeic acid significantly inhibited cell
      viability decrease induced by MPP(+), and caspase-3 fluorometric assay showed
      that caffeic acid efficiently suppressed caspase-3 activation in CGNs induced by
      MPP(+). CONCLUSION: Caffeic acid (CA) can significantly protect CGNs from
      apoptosis induced by MPP(+) and may provide a useful therapeutic strategy for the
      treatment of Parkinson's disease.

PMID- 14970884
TI  - [Studies on the biotransformation of escin Ia by human intestinal bacteria and
      the anti-tumor activities of desacylescin I].
AB  - OBJECTIVE: To study Biotransformation of escin Ia by the crude enzymes of human
      intestinal bacteria and Lactobacillus brevis, determine the structures of
      biotransformation products and assay the inhibitory effect of desacylescin I on
      the tumor cell growth. METHODS: The escin Ia was incubated with crude enzymes of
      human intestinal bacteria and Lactobacillus brevis in vitro, respectively. The
      biotransformation products were isolated and purified by the chromatographic
      methods and the structures were determined by the spectroscopic techniques.
      RESULTS: Escin Ia was converted into isoescin Ia, desacylescin I, 21beta-O
      tigloylprotoaescigenin and protoaescigenin by crude enzymes of human intestinal
      bacteria and Lactobacillus brevis. Desacylescin I showed potentially inhibitory
      effects on tumor cell growth of mouse sarcoma-180, hepatic carcinoma H(22) and
      lung carcinoma in vivo. CONCLUSION: The results suggest that Escin Ia was a
      prodrug and its structure can be converted by human intestinal bacteria and
      Lactobacillus brevis. Desacylescin I as a biotransformation product showed
      potentially inhibitory effects on mouse tumor, and a potential candidate for anti
      tumor agents.

PMID- 14970885
TI  - [Cellular mechanism of renal proximal tubular epithelial cell injury induced by
      aristolochic acid I and aristololactam I].
AB  - OBJECTIVE: To investigate the cellular mechanism of renal proximal tubular
      epithelial cell(PTEC) injury induced by aristolochic acid I (AA-I) and
      aristololactam I (AL-I). METHODS: Human PTEC cell line HK-2 was used as the
      subject. Cell apoptosis was evaluated by using FACS. Fibronectin (FN) and TGF
      beta1 levels were assayed in the supernatant from cultured HK-2 cells by ELISA.
      In the blocking study, anti-TGF-beta1 neutralizing antibody was used as an
      antagonist. The changes of FN level and apoptosis were compared. RESULTS: After
      stimulation by 2.5 mg/L AA-I, HK-2 cells secreted TGF-beta1 at hour 12 and FN at
      hour 36. HK-2 cell apoptosis was detected at hour 48. Anti-TGF-beta1 neutralizing
      antibody (5 mg/L) could suppress AA-I induced apoptosis by 63.7%(P<0.001), and it
      blocked AA-I induced FN secretion by 50.2%(P<0.001). In contrast, Anti-TGF-beta1
      neutralizing antibody had no effect on AL-I-induced apoptosis and FN secretion,
      even though AL-I (5 mg/L) had similar effect on these events compared to AA-I.
      CONCLUSION: The effects of AA-I on stimulating cell apoptosis and FN secretion
      are mediated by TGF-beta1. As the metabolite of that of AA-I, the cellular injury
      mechanism of AL-I is different from that of AA-I, although it has similar effects
      like AA-I. The effects of AL-I may be mediated by different mechanisms except TGF
      beta1 pathway.

PMID- 14970886
TI  - [Pharmacokinetics of honokiol in rats].
AB  - OBJECTIVE: To investigate the pharmacokinetics of honokiol in rats. METHODS:
      Honokiol injection was delivered by vein injection to SD-rats. The blood samples
      were gathered at a series of time  lags. Honokiol in rat plasma was determined
      with an RP-HPLC method and the data were analyzed with program 3P87. RESULTS:
      After i.v. injection of honokiol, concentration-time curves were fitted to a 3
      compartment model: with halftime of 2.8 min, 11.9 min, and 56.8 min. CONCLUSION:
      Honokiol was quickly distributed in rats after i.v. and the concentration
      decreased rapidly. Our studies provided important referrence to the research on
      the pharmacodynamics and the pharmaceutics of Honokiol.

PMID- 14970887
TI  - [Clinical analysis of 5 cases with acute intravascular hemolysis caused by
      puerarin].
AB  - OBJECTIVE: To explore the clinical characteristics of acute intravascular
      hemolysis caused by puerarin so as to help our prevention, diagnosis and
      treatment. METHODS: Analysis of 5 cases of acute intravascular hemolysis caused
      by puerarin was made and literature review conducted. RESULTS: All patients had
      the history of administering puerarin, with the pre-symptoms of acute hemolysis;
      the clinical characteristics of acute intravascular hemolysis were
      observed:sudden attacks of lumber and abdominal pain, chill, fever dyspnea,
      temporary conciousness loss, dark urine or hematuria, low hemoglobin, high
      reticular red blood cell, positive of Coombs' test. CONCLUSION: When sudden
      attacks of the above symptoms appear, the acute intravascular hemolysis should be
      taken into consideration first and the giving of the puerarin intravenously be
      immediately stopped Active and proper treatment should be made.

PMID- 14970888
TI  - Nociceptive responses of anterior cingulate cortical ensembles in behaving rats.
AB  - OBJECTIVE: To confirm the role of anterior cingulated cortices (ACC) in the
      coding of pain affect by exploring the neural ensemble coding pattern within the
      anterior cingulate cortex in behaving rats with a multichannel recording
      technique. METHODS: In five adult male Sprague-Dawley rats, two arrays of eight
      stainless steel microwires were bilaterally implanted into ACC. Noxious radiant
      heat stimulation was applied to the tail, bilateral fore-paws and hind-paws of
      freely moving rats. Neuroelectric signals were obtained from the microwires and
      sent to a multichannel recording device via cables and connectors. The time
      stamps of neuronal activities were stored on a personal computer for off-line
      analysis. RESULTS: Noxious heat stimuli evoked predominantly excitatory and
      sustained neural activity within ACC, reflecting the processing of pain
      unpleasantness; pain-related anticipatory responses could be seen near the
      stimulation start, indicating the behavioral preparation for escape; ACC neurons
      had broad receptive fields by showing quite similar pain-related responses to
      stimuli on either side of the hind-paw, suggesting that they are not eligible for
      the localization of a stimulus. CONCLUSION: ACC has played a major role in
      processing the affective-motivational aspect of pain.

PMID- 14970889
TI  - [Interaction between endogenous nitric oxide and hydrogen sulfide in pathogenesis
      of hypoxic pulmonary hypertension].
AB  - OBJECTIVE: To investigate the interaction between nitric (NO) / nitric oxygenase
      (NOS) and hydrogen sulfide (H(2)S)/ cystathionine-gamma-lyase (CSE) system in the
      pathogenesis of hypoxic pulmonary hypertension. METHODS: 25 rats were randomly
      divided into four groups: hypoxic group (n=7 ), hypoxic + L-NAME group (n=6 ),
      hypoxic + PPG group (n=6) and control group (n=6 ). After 21 days, pulmonary
      artery mean pressure (mPAP) of each rat was evaluated, and the plasma
      concentration of H(2)S and NO was measured. Meanwhile, the activities of CSE in
      pulmonary tissue in hypoxic, hypoxic + L-NAME and control groups were detected,
      respectively, and expressions of NOS in pulmonary arteries in hypoxic, hypoxic +
      PPG and control groups were also detected by immunohistochemistry technique.
      RESULTS: mPAP was significantly increased in hypoxic rats as compared with normal
      controls. Meanwhile, compared with controls, the production of NO and H(2)S in
      plasma, the activity of CSE in pulmonary tissue and expression of NOS in
      pulmonary arteries were markedly decreased in hypoxic rats. However, mPAP was
      significantly increased in hyopxic + L-NAME group as compared with hypoxic
      groups, and at the same time, the plasma concentration of NO was markedly
      decreased. However, the plasma concentration of H(2)S and the activity of CSE in
      pulmonary tissue in hyopxic+L-NAME group were increased significantly as compared
      with those of hypoxic group. PPG also worsened pulmonary hypertension of hypoxic
      rats, however,it increased endogenous production of NO and the expression of NOS
      of pulmonary arteries obviously. CONCLUSION: There is a negative feed back effect
      between NO/NOS system and H(2)S/CSE system in development of hypoxic pulmonary
      hypertension. They might interact with each other and therefore play an important
      regulating role in hypoxic pulmonary hypertension.

PMID- 14970890
TI  - [Effect of naloxone on remote seizure susceptibility].
AB  - OBJECTIVE: To evaluate the effect of low dose naloxone on remote seizure
      susceptibility after repeated febrile seizures(FS) in developing age. METHODS:
      Warm water induced rat FS model was developed in this study. Forty-nine SD rats
      were randomly divided into two groups: normal control group(n=10) and
      hyperthermic seizure group (n=39). The latter was further divided into FS control
      group (n=13) and naloxone-treated group (n=26). The dose of naloxone was
      different in the two naloxone-treated groups (13/each group). One group dose was
      1 mg/kg, and the other 2 mg/kg. Each rat of hyperthermic seizure groups was
      induced to have 7 febrile seizures at the interval of 1 day. The rats were
      weighed and injected intraperitoneally with naloxone once the FS occurred in
      naloxone-treated group, while the rats of other groups were injected with 0.9%
      sodium chloride. After the seventh stimulation, all rats were left un-stimulated
      for 2 months, then re-stimulated. Re-stimulated seizure incidence rate, seizure
      duration and seizure grade in different groups were observed and compared with
      each other. Hippocampal mossy fiber sprouting was detected by Timm stain.
      RESULTS: In naloxone-treated group, the rats' seizure duration and seizure grade
      [(5.66+/-2.78) min, (2.97+/-1.18)] significantly decreased (t=5.035, P<0.01;
      t=3.343, P<0.01) compared with those in FS control group [(21.18+/-4.06) min,
      (4.54+/-0.78)], although no significant gap was observed on seizure incidence
      rate(57.7%,84.6% respectively) and seizure latency between them. In non-treated
      group, in which two rats developed status epilepsy, the incident rate of the
      fifth grade seizure was 69.3%, much higher than 19.3% of naloxone treated group.
      Timm-stain pattern showed that the straining in the IML (inner molecular layer)
      of treated group rats was much lighter than that of non-treated group [(2.33+/
      1.03), (0.92+/-0.79), P<0.01]. CONCLUSION: Low dose naloxone used on naive rat
      with repeated febrile seizures can efficiently decrease the seizure
      susceptibility in the mature period and lighten the neural damage by twice-hit
      seizure in the mature period as well.

PMID- 14970891
TI  - [Human telomerase P53 estrogen and progesterone receptor expression in
      endometrial carcinoma].
AB  - OBJECTIVE: To study the role of hTERT and c-myc,P53,ER,PR in endometrial
      carcinoma carcinogenesis. METHODS: The expression of hTERT, c-myc mRNA, P53
      protein, ER and PR examined by in situ hybridization and immunohistochemistry in
      14 cases of endometrial simple hyperplasia, 10 of complex hyperplasia, 8 of
      atypical hyperplasia and 52 with endometrial carcinoma. RESULTS: (1) The positive
      rate of hTERT in simple, complex, atypical hyperplasia and carcinoma were 14.3%
      (2/14), 50.0% (4/8), 80.0% (8/10) and 92.3% (48/52), respectively. The prevalence
      and intensity of hTERT signal were greater in the carcinomas and atypical
      hyperplasia than those in simple or complex hyperplasia (P<0.05). The expressions
      of c-myc and P53 were similar to that of hTERT. (2) The expressions of hTERT, c
      myc, P53 and PR were significantly correlated with tumor differentiation. The
      expressions of c-myc and P53 in type I were significantly different from those in
      type II. The expression of c-myc with lymph node metastasis was significantly
      higher than that without metastasis. (3) The positive correlation between hTERT
      and c-myc was found in endometrial carcinoma (r=0.398 8, P<0.05); It was also
      found between hTERT and P53 in type II endometrial carcinoma (r=1.000, P<0.05).
      CONCLUSION: The expressions of hTERT, c-myc and P53 may be involved in the
      progression from the endometrial atypical hyperplasia to cancer. They may also be
      associated with the prognosis of endometrial carcinoma. c-myc and P53 may play a
      role in the transcriptive activation of hTERT gene in endometrial carcinoma.

PMID- 14970892
TI  - [Colorectal cancer patients have oligoclonal proliferation of T cells in blood].
AB  - OBJECTIVE: To study the clonal characteristics of peripheral T cells and anti
      tumor immunology in the patients with colorectal cancer by analyzing T cell
      receptor beta (TCRbeta) gene repertoire and complementarity determining regions 3
      (CDR3) amino acid sequence of the peripheral blood cells (PBL). METHODS: The 24
      TCRbetaV genes from PBL in pre-operation and post-operation and colorectal cancer
      tissues, were amplified by the method of combined reverse transcriptase
      polymerase chain reaction (RT-PCR) with denaturation polyacrylamide sequencing
      gel electrophoresis, which is called TCRbeta gene repertoire. In order to analyze
      the clonality of the over-expressing bands and the CDR3 sequence, the PCR
      production was sequenced directly. RESULTS: TCRbeta gene repertoire of PBL in the
      tumor-bearing patients was clonally expressed, which indicated that there were
      monoclonal or oligoclonal expansion of T lymphocytes. Some of the clonal T cells
      in PBL had the same CDR3 amino acid sequence motifs with the clonal T cells in
      the tumor infiltrating lymphocyte(TIL). The patients with clonal expansion of T
      cells in PBL had lymph node metastases, but there was no recurrence within 10
      months after operation. CONCLUSION: There is oligoclonal proliferation of T cells
      in the blood of tumor-bearing patients. It is possible that the clonal T
      lymphocytes are the tumor associated antigen specific anti-tumor T lymphocytes.

PMID- 14970893
TI  - [Effect of different isoforms of tocopherols on expression of intercellular
      adhesion molecule-1 in human umbilical vein endothelial cells].
AB  - OBJECTIVE: To observe the influence of different tocopherol isoforms on oxidized
      low density lipoprotein (oxLDL) or recombinant human C-reactive protein (rhCRP)
      induced expression of intercellular adhesion molecule-1 (ICAM-1) in human
      umbilical vein endothelial cells (HUVECs) and to investigate the potential
      mechanisms and effects of different tocopherols on atherosclerosis. METHODS:
      Cultured HUVECs were incubated with oxLDL, oxLDL + alpha-tocopherol, oxLDL +
      gamma-tocopherol, oxLDL + mixed-tocopherols, rhCRP, rhCRP + alpha-tocopherol,
      rhCRP + gamma-tocopherol rhCRP + mixed-tocopherols for 24 hours, respectively.
      The ICAM-1 expressions of protein and mRNA were detected by cell enzyme linked
      immunosorbent assay (ELISA), flow cytometric technique and RT-PCR. RESULTS:
      Incubation of HUVECs with oxLDL or rhCRP for 24 hours significantly increased
      ICAM-1 expressions of proteins and mRNA. The different tocopherols inhibited
      oxLDL-induced ICAM-1 expression in HUVECs in a concentration-dependent manner (50
      200 micromol/L) and mixed-tocopherols were more potent than alpha-tocopherol or
      gamma-tocopherol alone. However, rhCRP-induced ICAM-1 expression in HUVECs was
      not inhibited by tocopherols. CONCLUSION: The different tocopherols inhibited
      oxLDL-induced ICAM-1 expression in HUVECs and mixed-tocopherols were more potent
      than alpha-tocopherol or gamma-tocopherol alone, which may be important for the
      beneficial effects of tocopherols on atherosclerosis and cardiovascular disease.

PMID- 14970894
TI  - [Effects of early rehabilitation on activities of daily living and complications
      in acute stroke patients].
AB  - OBJECTIVE: To investigate the effects of early rehabilitation on activities of
      daily living (ADL) and complications in patients within 1 month after a first
      stroke. METHODS: 57 stroke patients were randomly divided into rehabilitation
      group (30 cases) and control group (27 cases). Patients in rehabilitation group
      received rehabilitation intervention (the main methods were therapeutic
      exercises, especially Bobath method) starting on average (15+/-4) days after
      stroke. Patients in both groups received the similar pharmological treatments.
      The demographic information was similar in both groups. Using the degree of
      deficit of neural function (DDNF,Chinese version), Barthel index and Fugl-Meyer
      Assessment (FMA) scale to assess all patients in pre-therapy stage and post
      therapy stage. RESULTS: The scores of DDNF, FMA and Barthel index except for the
      grooming item (P=0.04, it is higher in rehabilitation group than in control
      group) in the 2 groups were similar at the pre-therapy stage (P>0.05). At the
      post-therapy stage, there was no significant difference in the difference values
      in the grooming item between the pre- and post-stages in the 2 groups. There were
      significant differences in the difference values between the pre- and post-stages
      in the 2 groups in eating, bed-chair transfer and short distance walking
      activities items put together(P=0.05). The differences between the pre- and post
      stages in both groups in Barthel index items except the control of feces and
      urine, and bath items were significant (P</=0.01). The effects on complications
      were as follows: At the pre-therapy stage, the number of shoulder hand syndrome
      in rehabilitation group was higher than the one in control group (P=0.11), it was
      lower in rehabilitation group than in control group (P=0.09) at the post-therapy
      stage. There were no significant differences about drop foot, interior deviation
      foot and ankle joint contracture conditions between the 2 groups at the pre
      therapy stage, but there were significant differences about the 3 conditions at
      the post-therapy stage (P</=0.01), and the number of 3 complications was lower in
      rehabilitation group than in control group. There was no significant difference
      in shoulder subluxation at the pre- and post-therapy stages between the 2 groups.
      CONCLUSION: Early rehabilitation can effectively improve stroke patients' ADL,
      especially in eating, bed-chair transfer and short distance walking activities,
      and decrease the rate of complications' incidence within one month after stroke.

PMID- 14970895
TI  - [Expression and purification of recombinant N-terminal protein of SARS S1 subunit
      expressed in E. Coli].
AB  - OBJECTIVE: To express and purify the recombinant N-terminal protein of SARS virus
      S1 subunit and to study its role in SARS immune response. METHODS: The gene
      encoding N-terminal 334 amino acid residuals of SARS virus S1 subunit was cloned
      and expressed in E. Coli. After purification, the recombinant protein was
      identified by anti-SARS positive sera from recovered SARS patients. The sera from
      health donors, which were collected before the out-break of SARS, were used as
      negative control in the study. RESULTS: Sequencing analysis confirmed that the
      desired DNA sequence in recombinant plasmid was correct and had the same sequence
      of natural N-terminal of SARS virus S1 subunit. The molecular weight of
      recombinant fusion protein is about 64 000. The recombinant S1 protein could
      react with three antibody positive samples from recovered SARS patients, which
      showed specific bands at 64 000, but not with the control samples according to
      results of western blot. CONCLUSION: The recombinant N-terminal protein of SARS
      virus S1 subunit displays specific reaction with SARS antibody and may provide a
      good tool for further research of immune response to SARS virus.

PMID- 14970896
TI  - [Progress in biotransformation of triptolides and bufadienolides].
AB  - The latest results from our research group in the biotransformation of
      triptolides and bufadienolides were reviewed. The trends in the development of
      biotransformation in the future were also briefly discussed.

PMID- 14970897
TI  - [Applied fundamental research of echinacea species].
AB  - Echinacea is a most famous "immune herb" in western countries, and continues to
      be the best selling herb for many years. For the last five years, our research
      group has cooperated with Institute of Medicinal Plants in Huairou District of
      Beijing, carrying out studies on Echinacea purpurea, which involved botany,
      cultivation, pharmacognosy, phytochemistry, quality control, pharmacology and
      toxicology of the species. Two other species introduced from Canada, Echinacea
      angustifolia and Echinacea pallida, were also included in the taxonomic,
      cultivated and pharmacognostic studies. The results acquired have opened up the
      path to introduce Echinacea species into Traditional Chinese Medicine, thus
      established the possibility of developing more promising drugs from them.

PMID- 14970898
TI  - [Structural characteristics and spectroscopic profiles of xanthones from
      Polygala].
AB  - Through studies of xanthones from Polygla tenuifolia, one of the main medicinal
      plants of Polygala, the structural characteristics and spectroscopic rules
      (including IR, UV, (1)H NMR and (13)C NMR data) of xanthones from Polygala were
      summarized, combined with the reference reports of this type of compounds from
      the other plants of Polygala. It is helpful to the structure elucidation of
      xanthones.

PMID- 14970899
TI  - [Culture of osteoblasts by serial explant culture and comparison of their
      characteristics].
AB  - OBJECTIVE: To Investigate a simple, economical and efficient method of primary
      osteoblast culture and compare their characteristics. METHODS: Primary
      osteoblasts of 1 st-4 th series explant culture from calvarial bones of neonatal
      Sprague-Dawley rats, were collected and osteoblasts shape, mitosis,
      proliferation, ALP activity and immunohistological expression of osteocalcin and
      BMP-2 observed. RESULTS: No difference was found in cell shape, spread,
      confluence, ALP activity as well as immunohistological stain of osteocalcin and
      BMP-2 of the osteoblasts, which had been harvested from the 1 st-4 th series
      explant cultures of Sprague-Dawley rats. CONCLUSION: Series explant culture can
      harvest the same kind of osteoblasts as the explant culture, and more osteoblasts
      can be obtained at a single time. It saves money and time and is easy to
      manipulate.

PMID- 14970900
TI  - [Human gingival epithelial cells cultured by a combined method of serum
      containing medium and serum free medium].
AB  - OBJECTIVE: To search for a simple and rapid cell culture method for human
      gingival epithelial cells with a high success rate. METHODS: Culture medium
      containing serum has been proved to have the ability of accelerating the early
      adhesion of human gingival tissue blocks, and the migration of gingival
      epithelial cells from the rim of the blocks. By means of this, we introduced the
      serum containing DMEM to the cell culture medium within the first 7-10 days, and
      changed with serum free cell culture medium to accelerate the mitosis,
      proliferation, and migration of the gingival epithelial cells, which had moved
      out from the tissue blocks. Using the combined method, cells were identified by
      the method of morphology, immunohistochemistry and analysis of the cell growth
      curve, as well as SEM. Compared study of the effects on the cell growth between
      combined method and serum containing DMEM or serum free EpiLife culture method
      was conducted. RESULTS: Cells were harvested within 17-22 days. Primary culture
      success rate was 90.6%. Cultured cells were slabstone-shaped.
      Immunohistochemistry analysis of keratin antibody showed a positive result. The
      cells had stronger ability of migration and proliferation in the serum free cell
      culture medium compared with that in the serum medium. CONCLUSION: This method
      can culture the gingival epithelium cells conveniently with accelerated speed.

PMID- 14970901
TI  - [Hydrogen sulfide: a novel cardiovascular functional regulatory gas factor].
AB  - Hydrogen sulfide (H(2)S) may be endogenously produced by cystathionine beta-lyase
      (CBS) and cystathionine gamma-lyase (CSE) as a cardiovascular physiological
      functional factor. On the hypoxic pulmonary hypertension (HPH) animal model, the
      plasma H(2)S concentration, the gene expression and the activity (CSE) were
      decreased in lung tissues   In L-NAME induced hypertension and spontaneous
      hypertension rats (SHR) models, the plasma H(2)S concentration, vascular CSE
      activity and mRNA expression were obviously decreased. When H(2)S was exogenously
      supplied, systolic pressure obviously decrease. These studies suggested that
      CSE/H(2)S pathway participated in the pathophysiological development of
      hypertension. The endogenous level of H(2)S produced by some arterial tissues
      increased in both septic and endotoxic shock rats. The level of H(2)S highly
      correlated with the endogenous level of NO. These results suggest that H(2)S may
      be a novel cardiovascular functional regulator.

PMID- 14970902
TI  - Potential of peroxynitrite to promote the conversion of oxyhemoglobin to
      methemoglobin.
AB  - Superoxide anion and NO can react to form the highly oxidizing species
      peroxynitrite (ONOO-) which can react directly with hemoglobin (Hb) even in the
      presence of physiological concentration CO2. This research was to determine the
      ONOO- -mediated oxidation damage to the heme of oxyhemoglobin (oxyHb) under
      conditions expected in blood. Results showed that 8-10 mol ONOO- was needed to
      quickly and completely convert 1 mol oxyHb to methemoglobin (metHb). ONOO- (20
      140 microM) caused rapid and extensive formation of metHb from oxyHb (50 microM)
      mainly occurring within first 5-20 min of incubation. The conversion efficiency
      reached 16%, 48%, 60%, 79% and 88% output of metHb after 90 min of incubation at
      0, 20, 40, 100, and 140 microM ONOO- respectively. 1 mM CO2 caused a small
      decrease in the ability of ONOO- to oxidize oxyHb, and ONOO- -promoted conversion
      of oxyHb to metHb increased when pH decreased from 8.0 to 6.0. Relatively lower
      temperature in blood condition will inhibit this reaction in some degree. We
      postulate that ONOO- can mediate oxidation damage to the heme, and cause heme
      loss from the hydrophobic cavity of Hb when its concentration exceeded 90 microM.
      These results indicated that ONOO- could convert oxyHb to metHb under the
      conditions expected in blood, and this reaction was regulated by CO2
      concentration, reaction time, temperature and pH value.

PMID- 14970903
TI  - Molecular cloning of TSARG6 gene related to apoptosis in human spermatogenic
      cells.
AB  - Beginning from a mouse EST (GenBank accession No. BE644537) which was
      significantly up-regulated in cryptorchidism and represented a novel gene, we
      cloned a new gene (GenBank accession No. AY138810) which is related to apoptosis
      in human spermatogenic cells by means of GeneScan program and PCR technology. The
      gene whose full cDNA length is 1875 bp containing 8 exons and 7 introns is
      located in human chromosome 11q13.3. Its protein containing 316 amino acid
      residues is a new member of HSP40 protein family because the sequence contains
      the highly conserved J domain which is present in all DnaJ-like proteins and is
      considered to have a critical role in DnaJ-DnaK protein-protein interactions.
      TSARG6 protein displays a 45% identity in a 348-amino acid overlap with
      DJB5_HUMAN protein. The result of RT-PCR and Northern blot analysis showed that
      TSARG6 is specifically expressed in adult testis and the transcript is 1.8 kb.
      Based upon all these observations, it is considered that we cloned a new gene
      which probably inhibited human testis spermatogenesis apoptosis.

PMID- 14970904
TI  - Effect of Zn(II) on the structure and biological activity of natural beta-NGF.
AB  - Only beta-NGF, the subunit of the 7S NGF complex, exhibits NGF activity, but the
      function of the zinc ion in native beta-NGF has received little attention.
      Flameless atomic absorption spectroscopy (FAAS) measurements reveal that native
      beta-NGF contains Zn(II) with a Zn(II)/beta-NGF stoichiometry of 1:14.6. The
      presence of Zn(II) in the native molecule results in significant changes of the
      secondary structure and local tertiary structure around Trp(s) with respect to
      those of apo beta-NGF, as suggested by spectra of fluorescence and circular
      dichrosim. Stopped-flow studies show that there are at least two steps during the
      interaction of Zn(II) with the apo form. In comparison with its apo form, the
      native beta-NGF shows a higher ability to trigger the proliferation of TF1 cells
      and mediate the survival of PC12. Thus it is most likely that the structural
      changes caused by the presence of Zn(II) directly lead to the increase in the
      biological activity of beta-NGF. All results indicate that Zn(II) in native beta
      NGF plays an important role in the structure and the biological activity of the
      protein.

PMID- 14970905
TI  - Preparation and primary application of monoclonal antibodies against a novel
      ribosome-inactivating protein Moschatin from pumpkin seeds.
AB  - Plant ribosome-inactivating proteins (RIPs) have multiple biological functions,
      and have been widely used in the studies on biomedical and agronomic
      applications. Moschatin is a novel single-chain RIP recently purified from
      pumpkin seeds, and it has been successfully applied to construct the immunotoxin
      that can selectively kill the cultured human melanoma cells. Six stable strains
      of hybridomas (2H8, 4A8, 5B6, 6F8, 4H10 and 6C2) that can secrete high specific
      monoclonal antibodies against Moschatin have been successfully prepared using
      hybridoma technique. The isotypes of these monoclonal antibodies are IgG1, IgG1,
      IgG1, IgG1, IgG2a and IgGM. Their affinity constants were determined to be
      1.42x10(8), 2.71x10(8), 8.72x10(7), 2.06x10(8), 1.36x10(8) and 1.51x10(8) M(-1)
      in a sequent order, measured by non-competitive ELISA. The monoclonal antibody
      4A8 has been used to detect Moschatin in Western blot. An immunoaffinity gel,
      which consisted of a monoclonal antibody 4H10 and Sepharose 4B, was prepared and
      used to purify Moschatin from pumpkin seeds crude extract.

PMID- 14970906
TI  - Molecular characterization of a new lectin from the marine alga Ulva pertusa.
AB  - A new lectin, named UPL1, was purified from a green alga Ulva pertusa by an
      affinity chromatography on the bovine-thyroglobulin-Sepharose 4B column. The
      molecular mass of the algal lectin was about 23 kD by SDS-PAGE, and it
      specifically agglutinated rabbit erythrocytes. The hemagglutinating activity for
      rabbit erythrocytes could be inhibited by bovine thyroglobulin and N-acetyl-D
      glucosamine. The lectin UPL1 required divalent cations for maintenance of its
      biological activity, and was heat-stable, and had higher activity within pH 6-8.
      The N-terminal amino acid sequence of the purified lectin was determined (P83209)
      and a set of degenerate primers were designed. The full-length cDNA of the lectin
      was cloned by rapid amplification of cDNA ends (RACE) method (AY433960). Sequence
      analysis of upl1 indicated it was 1084 bp long, and encoded a premature protein
      of 203 amino acids. The N-terminal sequence of the mature UPL1 polypeptide
      started at amino acid 54 of the deduced sequence from the cDNA, indicating 53
      amino acids lost due to posttranslational modification. The primary structure of
      the Ulva pertusa lectin did not show amino acid sequence similarity with known
      plant and animal lectins. Hence, this protein may be the paradigm of a novel
      lectin family.

PMID- 14970907
TI  - Purification and characterization of recombinant sTRAIL expressed in Escherichia
      coli.
AB  - As a potential anti-tumor protein, tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) has drawn considerable attention. This report presented
      the purification and characterization of soluble TRAIL, expressed as inclusion
      bodies in E. coli. sTRAIL inclusion bodies were solubilized and refolded at a
      high concentration up to 0.9 g/L by a simple dilution method. Refolded protein
      was purified to electrophoretic homogeneity by a single-step immobilized metal
      affinity chromatography. The purified sTRAIL had a strong cytotoxic activity
      against human pancreatic tumor cell line 1990, with ED50 about 1.5 mg/L. Circular
      dichroism and fluorescence spectrum analysis showed that the refolded sTRAIL had
      a structure similar to that of native protein with beta-sheet secondary
      structure. This efficient procedure of sTRAIL renaturation may be useful for the
      mass production of this therapeutically important protein.

PMID- 14970908
TI  - The inhibitory role of lactacystin and beta-lactacystin on T-cell activation and
      proliferation.
AB  - To evaluate the effects of proteasome inhibitors lactacystin (LAC) and beta
      lactacystin (beta-LAC) on the proliferation and activation of T lymphocytes, flow
      cytometry was used to analyze the proliferation and the expression of CD69, CD25
      and CD3 of T lymphocytes activated by PHA. Furthermore, the expressions of PA28
      and IL-2 mRNA were assayed by competitive RT-PCR. The results indicated that: (1)
      LAC and beta-LAC significantly decreased the incorporation of BrdU and inhibited
      T lymphocytes proliferation in T lymphocytes activated by PHA; (2) although LAC
      and beta-LAC did not affect the expression of CD69 at any time, they
      significantly inhibited the expression of CD25 (48 h, 72 h, P<0.05); (3) in
      comparison with control, LAC and beta--LAC significantly down-regulated the
      expression of PA28 and IL-2 mRNA (48 h, 72 h, P<0.05). LAC and beta-LAC
      significantly inhibited the proliferation and activation of T cells. Mechanisms
      involved are inhibition of CD25 and down-regulation of PA28 and IL-2 mRNA
      expressions.

PMID- 14970909
TI  - An engineered PrPsc-like molecule from the chimera of mammalian prion protein and
      yeast Ure2p prion-inducing domain.
AB  - Production of the pathogenic prion isoform PrPsc-like molecules is thought to be
      useful for understanding the mysterious mechanism of conformational conversion
      process of prion diseases and proving the "protein-only" hypothesis. In this
      report, an engineered PrPsc-like conformation was produced from a chimera of
      mammalian bovine prion protein (bPrP) and yeast Ure2p prion-inducing domain
      (UPrD). Compared with the normal form of bPrP, the engineered recombinant
      protein, termed bPrP-UPrD, spontaneously aggregated into ordered fibrils under
      physiological condition, displaying amyloid-like characteristics, such as
      fibrillar morphology, birefringence upon binding to Congo red and increased
      fluorescence intensity with Thioflavine T. Limited resistance to protease K
      digestion and CD spectroscopy experiments suggested that the structure of bPrP
      UPrD had been changed, and adopted a new, high content beta-sheet conformation
      during the fibrils formation. Moreover, bPrP-UPrD amyloid fibrils could recruit
      more soluble forms into the aggregates. Therefore, the engineered molecules could
      mimic significant behaviors of PrPsc and will be helpful for further
      understanding the mechanism of conformational conversion process.

PMID- 14970910
TI  - Hypoxia inducible factor-1 alpha correlates the expression of heme oxygenase 1
      gene in pulmonary arteries of rat with hypoxia-induced pulmonary hypertension.
AB  - To test the hypothesis that hypoxia inducible factor-1 alpha (HIF-1alpha) up
      regulated the expression of heme oxygenase-1 (HO-1) gene in pulmonary arteries of
      rats with hypoxia-induced pulmonary hypertension, 8 male Wistar rats in each of 5
      groups were exposed to hypoxia for 0, 3, 7, 14 or 21 d, respectively. Mean
      pulmonary arterial pressure (mPAP), vessel morphometry and right ventricle
      hypertrophy index were measured. Lungs were inflation fixed for
      immunohistochemistry, in situ hybridization; frozen for later measurement of HO-1
      enzyme activity. mPAP increased significantly after 7 d of hypoxia [(18.4 +/-
      0.4) mmHg, P<0.05], reaching its peak after 14 d of hypoxia, then remained
      stable. Pulmonary artery remodeling became to develop significantly after 14 d of
      hypoxia. HIF-1alpha protein in control was poorly positive (0.05 +/- 0.01), but
      was up-regulated in pulmonary arterial tunica intima of all hypoxic rats. In
      pulmonary arterial tunica media, the levels of HIF-1alpha protein were markedly
      up-regulated after 3 d and 7 d of hypoxia (0.20 +/- 0.02; 0.22 +/- 0.02, P<0.05),
      then declined after 14 d and 21 d of hypoxia. HIF-1alpha mRNA staining was poorly
      positive in control, hypoxia for 3 and 7 d, but enhanced significantly after 14 d
      of hypoxia (0.20 +/- 0.02, P<0.05), then remained stable. HO-1 protein increased
      after 7 d of hypoxia (0.10 +/- 0.01, P<0.05), reaching its peak after 14 d of
      hypoxia (0.21 +/- 0.02, P<0.05), then remained stable. HO-1 mRNA increased after
      3 d of hypoxia, reaching its peak after 7 d of hypoxia (0.17 +/- 0.01, P<0.05),
      then declined. Linear correlation analysis showed that HIF-1alpha mRNA, HO-1
      protein and mPAP were associated with pulmonary remodeling. HIF-1alpha protein
      (tunica intima) was conversely correlated with HIF-1alpha mRNA (r=0.921,P<0.01),
      HO-1 protein was conversely correlated with HIF-1alpha protein (tunica intima)
      (r=0.821, P<0.01). HIF-1alpha and HO-1 were both involved in the pathogenesis of
      hypoxia-induced pulmonary hypertension in rat. Hypoxia inducible factor-1 alpha
      correlated the expression of heme oxygenase 1 gene in pulmonary arteries of rat
      with hypoxia-induced pulmonary hypertension.

PMID- 14970911
TI  - Refolding and characterization of recombinant human GST-PD-1 fusion protein
      expressed in Escherichia coli.
AB  - Programmed death-1 (PD-1) is a costimulatory molecule of CD28 family expressed on
      activated T, B and myeloid cells. The engagement of PD-1 with its two ligands, PD
      L1 and PD-L2, inhibits proliferation of T cell and production of a series of its
      cytokines. The blockade of PD-1 pathway is involved in antiviral and antitumoral
      immunity. In this study, human PD-1 cDNA encoding extracellular domain was
      amplified and cloned into expression plasmid pGEX-5x-3. The fusion protein GST-PD
      1 was effectively expressed in E. coli BL21 (DE3) as inclusion bodies and a
      denaturation and refolding procedure was performed to obtain bioactive soluble
      GST-PD-1. Fusion protein of above 95% purity was acquired by a convenient two
      step purification using GST affinity and size exclusion columns. Furthermore, a
      PD-L1-dependent in vitro bioassay method was set up to characterize GST-PD-1
      bioactivity. The results suggested that GST-PD-1 could competently block the
      interaction between PD-L1 and PD-1 and increase the production of IL-2 and IFN
      gamma of phytohemagglutinin-activated T cells.

PMID- 14970912
TI  - [Myocardial regeneration after myocardial infarction--the speculation continues].

PMID- 14970913
TI  - [Mobilization of stem cells by granulocyte colony-stimulating factor for the
      regeneration of myocardial tissue after myocardial infarction].
AB  - BACKGROUND AND OBJECTIVE: Animal data suggest that mobilized bone marrow cells
      (BMC) may contribute to tissue regeneration after myocardial infarction (MI).
      However the safety, feasibility and efficacy of treatment with granulocyte colony
      stimulating factor (G-CSF) to mobilize BMC after acute myocardial infarction in
      patients is unknown. We analysed cardiac function and perfusion in 5 patients who
      were treated with G-CSF in addition to standard therapeutical regimen. METHODS
      AND RESULTS: 48 h after successful recanalization and stent implantation in 5
      patients with acute MI, the patients received 10 micro g/kg bodyweight/day G-CSF
      subcutaneously for a mean treatment duration of 7.6+/-0.5 days. Peak value of
      CD34 (+) cells, a multipotent subfraction of bone marrow cells, was reached after
      5.0+/-0.7 days. After 3 months of follow-up global left ventricular ejection
      fraction (determined by radionuclid-ventriculography) increased significantly
      from 42.2+/-6.6 % to 51.6+/-8.3 % (P<0.05). The wall motion score and the wall
      perfusion score (determined by ECG gated SPECT) decreased from 13.5+/-3.6 to
      9.9+/-3.5 (P<0.05) and from 9.6+/-2.9 to 7.0+/-4.5 (P<0.05), respectively,
      indicating a significant improvement of myocardial function and perfusion. No
      severe side effects of G-CSF treatment could be observed. Malignant arrhythmias
      were not observed either. CONCLUSION: In patients with acute MI, treatment with G
      CSF to mobilize BMC appears to be well tolerable under clinical conditions.
      Improved cardiac function and perfusion may be attributed to BMC-associated
      promotion of myocardial regeneration and neovascularization.

PMID- 14970914
TI  - [How frequent are diabetes-related amputations of the lower limbs in Germany? An
      analysis on the basis of routine data].
AB  - BACKGROUND AND OBJECTIVE: The total number of lower limb amputations in Germany
      as well as the frequency of lower limb amputations attributable to diabetes is
      unknown. Currently available estimates are based on regional studies resulting in
      different totals. The aim of this study was to perform a census of all lower limb
      amputations in Germany in order to obtain valid estimates of the number of
      amputations attributable to diabetes mellitus in Germany. PATIENTS AND METHODS:
      Hospital performance and expenditure statistics were used to obtain a
      comprehensive count of lower limb amputations. The number of amputations in
      diabetic patients as well as the number of diabetes-related amputations were
      assessed by calculating the proportion of diabetes among amputees as well as
      attributable amputations standardized to the age and gender distribution in
      Germany in 2001, using routine data from the Local Health Insurance Funds (AOK)
      as well as previous analyses from Germany. RESULTS: In 2001, 43,544 lower limb
      amputations and additional 3,981 revisions of amputations were performed in
      Germany. Among these almost 29,000 lower limb amputations were estimated to be
      performed in diabetic patients. More than 26,000 lower limb amputations per year
      were estimated to have been attributable to pre-existing diabetes mellitus.
      CONCLUSIONS: Lower limb amputations as a complication of diabetes mellitus are
      more frequent in Germany than previously estimated. Intensified prevention and
      therapy--as intended in disease management programs--are urgently needed to
      decrease the complications of diabetes and ultimately to reduce diabetes mellitus
      related costs.

PMID- 14970915
TI  - [Ptosis and ophthalmoplegia as predominant signs of multiple myeloma].
AB  - HISTORY AND ADMISSION FINDINGS: A 59-year-old woman was diagnosed as having
      solitary bone plasmacytoma of the sternum which was resected. Five month later
      she presented with a pathological fracture of the clavicle. On examination she
      had a ptosis and an ophthalmoplegia. INVESTIGATIONS: A mass in the clivus
      extending into the left sphenoid sinus as well as multiple osteolytic lesions in
      the skull were shown by cranial MRI. Skeletal survey showed multiple osteolytic
      lesions. Laboratory test did not show any specific abnormalities. DIAGNOSIS,
      TREATMENT AND COURSE: The biopsy taken from the mass at the sphenoid sinus
      demonstrated plasmacytoma. The diagnosis of multiple myeloma was based on the
      histological evidence of plasmacytoma and the occurrence of multiple lytic bone
      lesions although no infiltration of bone marrow and none of the specific
      laboratory findings were present. The patient underwent local radiotherapy with
      30 Gy followed by systemic chemotherapy. The symptoms regressed completely under
      this therapy. CONCLUSION: Various cranial nerve syndromes such as the superior
      orbital fissure syndrome are most often caused by tumors at the skull base.
      Knowledge of the histological entity is essential for the correct diagnosis and
      the appropriate therapy because rare tumors like multiple myeloma may also cause
      such syndromes.

PMID- 14970916
TI  - [Aspirin--a suitable drug for cancer prevention?].

PMID- 14970917
TI  - [Helicobacter treatment. Proven and new antibiotic combinations for the treatment
      of recurrences].

PMID- 14970918
TI  - [Arterial stiffness in arterial hypertension. A new risk factor for left
      ventricular hypertrophy and cardiac insufficiency?].

PMID- 14970919
TI  - [Patient autonomy--a critical concept analysis].

PMID- 14970920
TI  - Exploring developmental modes in a fossil arthropod: growth and trunk
      segmentation of the trilobite Aulacopleura konincki.
AB  - Trilobites offer the opportunity to explore postembryonic development within the
      fossil record of arthropod evolution. In contrast to most trilobites, the
      Silurian proetid Aulacopleura konincki from the Czech Republic exhibits marked
      variation in the mature number of thoracic segments, with five morphs with 18-22
      thoracic segments. The combination of abundant articulated specimens available
      from a narrow stratigraphic interval and segmental intraspecific variation makes
      this trilobite singularly useful for studying postembryonic growth and
      segmentation. Trunk segmentation followed a hemianamorphic pattern, as seen in
      other arthropods and as characteristic of the Trilobita; during a first
      anamorphic phase, segments were accreted, while in the subsequent epimorphic
      phase, segmentation did not proceed further despite continued growth. Size
      increment during the anamorphic phase was targeted and followed Dyar's rule, a
      geometric progression typical of many arthropods. We consider alternative
      hypotheses for the control of the switch from anamorphic to epimorphic phases of
      development. Our analysis favors a scenario in which the mature number of
      thoracic segments was determined quite early in development rather than at a late
      stage in association with a critical size threshold. This study demonstrates that
      hypotheses concerning developmental pattern and control can be tested in
      organisms belonging to an extinct clade.

PMID- 14970921
TI  - Trade-offs during the development of primary and secondary sexual traits in a
      horned beetle.
AB  - Resource allocation trade-offs during development affect the final sizes of adult
      structures and have the potential to constrain the types and magnitude of
      evolutionary change that developmental processes can accommodate. Such trade-offs
      can arise when two or more body parts compete for a limited pool of resources to
      sustain their growth and differentiation. Recent studies on several
      holometabolous insects suggest that resource allocation trade-offs may be most
      pronounced in tissues that grow physically close to each other. Here we examine
      the nature and magnitude of developmental trade-offs between two very distant
      body parts: head horns and genitalia of males of the horned scarab beetle
      Onthophagus taurus. Both structures develop from imaginal disklike tissues that
      undergo explosive growth during late larval development but differ in exactly
      when they initiate their growth. We experimentally ablated the precursor cells
      that normally give rise to male genitalia at several time points during late
      larval development and examined the degree of horn development in these males
      compared to that of untreated and sham-operated control males. We found that
      experimental males developed disproportionately larger horns. Horn overexpression
      was weakest in response to early ablation and most pronounced in males whose
      genital disks were ablated just before larvae entered the prepupal stage. Our
      results suggest that even distant body parts may rely on a common resource pool
      to sustain their growth and that the relative timing of growth may play an
      important role in determining whether, and how severely, growing organs will
      affect each other during development. We use our findings to discuss the
      physiological causes and evolutionary consequences of resource allocation trade
      offs.

PMID- 14970922
TI  - On the generality of the latitudinal diversity gradient.
AB  - The decline of biodiversity with latitude has received great attention, but both
      the concise pattern and the causes of the gradient are under strong debate. Most
      studies of the latitudinal gradient comprise only one or few organism types and
      are often restricted to certain region or habitat types. To test for significant
      variation in the gradient between organisms, habitats, or regions, a meta
      analysis was conducted on nearly 600 latitudinal gradients assembled from the
      literature. Each gradient was characterized by two effect sizes, strength
      (correlation coefficient) and slope, and additionally by 14 variables describing
      organisms, habitats, and regions. The analysis corroborated the high generality
      of the latitudinal diversity decline. Gradients on regional scales were
      significantly stronger and steeper than on local scales, and slopes also varied
      with sampling grain. Both strength and slope increased with organism body mass,
      and strength increased with trophic level. The body mass-effect size relation
      varied for ecto- versus homeotherm organisms and for different dispersal types,
      suggesting allometric effects on energy use and dispersal ability as possible
      mechanisms for the body mass effect. Latitudinal gradients were weaker and less
      steep in freshwater than in marine or terrestrial environments and differed
      significantly between continents and habitat types. The gradient parameters were
      not affected by hemisphere or the latitudinal range covered. This analysis is the
      first to describe these general and significant patterns, which have important
      consequences for models aiming to explain the latitudinal gradient.

PMID- 14970923
TI  - The analysis of variation of mtDNA hypervariable region 1 suggests that Eastern
      and Western Pygmies diverged before the Bantu expansion.
AB  - The Eastern Pygmies from Zaire and Western Pygmies from Cameroon, Congo, and the
      Central African Republic represent the two principal groups of African Pygmies.
      In the "recent divergence" hypothesis in which Western Pygmies are thought to be
      the result of hybridization between the ancestors of Eastern Pygmies and Bantu
      farmers who penetrated the equatorial belt and came into contact with Pygmies
      around 2-3 kiloyears ago. On the basis of recent archaeological research in the
      tropical rain forest, we propose a "pre-Bantu divergence" hypothesis, which
      posits the separation between the ancestors of Eastern and Western Pygmies
      earlier than 18 kiloyears ago. In order to test the two hypotheses, we analyzed
      the variation of the hypervariable region 1 of the mitochondrial DNA in the
      Mbenzele, Western Pygmies of the Central African Republic, and compared our
      results with those of previous mtDNA and Y chromosome studies. Distribution,
      sequence variation, and age of haplogroups along with genetic distances among
      populations, estimates of divergence times, and simulations based on the
      coalescent approach were found to be congruent with the pre-Bantu divergence but
      failed to support the recent divergence hypothesis.

PMID- 14970924
TI  - History and the species-area relationship in Lesser Antillean birds.
AB  - We examined the species-area relationship for three historically distinct subsets
      of Lesser Antillean birds identified by molecular phylogenetic analysis of island
      and continental populations. The groups comprised recent colonists from
      continental or Greater Antillean source populations, old taxa having recently
      expanded distributions within the Lesser Antilles, and old endemic taxa lacking
      evidence of recent dispersal between islands. The number of young taxa was
      primarily related to distance from the source of colonists in South America. In a
      multiple regression, the logarithmic slope of the species-area relationship for
      this group was shallow (0.066+/-0.016). Old endemic taxa were restricted to
      islands with high elevation, and within this subset, species richness was related
      primarily to island area, with a steep slope (0.719+/-0.110). The number of
      recently spread endemic taxa was related primarily to island elevation,
      apparently reflecting the persistence of such populations on islands with large
      areas of forested and montane habitats. Historical analysis of the Lesser
      Antillean avifauna supports the dynamic concept of island biogeography of
      MacArthur and Wilson, rather than the more static view of David Lack, in that
      colonists exhibit dispersal limitation and extinction plays a role in shaping
      patterns of diversity. However, the avifauna of the Lesser Antilles is probably
      not in equilibrium at present, and the overall species-area relationship might
      reflect changing proportions of historically distinguishable subsets of species.

PMID- 14970925
TI  - Priority versus brute force: when should males begin guarding resources?
AB  - When should males begin guarding a resource when both resources and guarders vary
      in quality? This general problem applies, for example, to migrant birds occupying
      territories in the spring and to precopula in crustaceans where males grab
      females before they molt and become receptive. Previous work has produced
      conflicting predictions. Theory on migrant birds predicts that the strongest
      competitors should often arrive first, whereas some models of mate guarding have
      predicted that the strongest competitors wait and then simply usurp a female from
      a weaker competitor. We build a general model of resource guarding that allows
      varying the ease with which takeovers occur. The model is phrased in terms of
      mate-guarding crustaceans, but the same logic can be applied to other forms of
      resource acquisition where priority plays a role but takeovers might be possible
      too. The race to secure breeding positions can lead to strong competitors (large
      males) taking females earliest, even though this means accepting a lower-quality
      female. Paradoxically, this means that small males, which have fewer breeding
      opportunities, are more choosy than larger ones. Such solutions are found when
      takeovers are impossible. The easier the takeovers and the higher the rate of
      finding guarded resources, the more likely are solutions where guarding durations
      are short, where strong competitors begin guarding only just before breeding, and
      where they do this by usurping the resource. The relationship between an
      individual's competitive ability and its timing of resource acquisition can also
      be nonlinear if takeovers are moderately common; if this is the case, then males
      of intermediate size guard the longest.

PMID- 14970926
TI  - Allee effects, immigration, and the evolution of species' niches.
AB  - Theoretical studies of adaptation to sink environments (with conditions outside
      the niche requirements of a species) have shown that immigration from source
      habitats can either facilitate or inhibit local adaptation. Here, we examine the
      influence of immigration on the evolution of local adaptation, given an Allee
      effect (i.e., at low densities, absolute fitness increases with population
      density). We consider a deterministic model for evolution at a haploid locus, and
      a stochastic individual-based model for evolution of a quantitative trait, and
      several kinds of Allee effects. We demonstrate that increased immigration can
      greatly facilitate adaptive evolution in the sink; with greater immigration,
      local population sizes rise, and because of the Allee effect, there is a positive
      indirect effect of immigration on local fitness. This makes it easier for alleles
      of modest effect to be captured by natural selection, transforming the sink into
      a locally adapted population that can persist without immigration.

PMID- 14970927
TI  - Comparing alternative models to empirical data: cognitive models of western scrub
      jay foraging behavior.
AB  - Animals often select one item from a set of candidates, as when choosing a
      foraging site or mate, and are expected to possess accurate and efficient rules
      for acquiring information and making decisions. Little is known, however, about
      the decision rules animals use. We compare patterns of information sampling by
      western scrub-jays (Aphelocoma californica) when choosing a nut with three
      decision rules: best of n (BN), flexible threshold (FT), and comparative Bayes
      (CB). First, we use a null hypothesis testing approach and find that the CB
      decision rule, in which individuals use past experiences to make nonrandom
      assessment and choice decisions, produces patterns of behavior that more closely
      correspond to observed patterns of nut sampling in scrub-jays than the other two
      rules. This approach does not allow us to quantify how much better CB is at
      predicting scrub-jay behavior than the other decision rules. Second, we use a
      model selection approach that uses Akaike Information Criteria to quantify how
      well alternative models approximate observed data. We find that the CB rule is
      much more likely to produce the observed patterns of scrub-jay behavior than the
      other rules. This result provides some of the best empirical evidence of the use
      of Bayesian information updating by a nonhuman animal.

PMID- 14970928
TI  - The evolutionary economics of immunity.
AB  - How much of its resources should an individual invest in a costly immune system?
      In this article, we apply an evolutionarily stable strategy analysis to an
      epidemic model to answer this question. On the one hand, an investment in immune
      function confers protection to infectious agents by reducing host susceptibility,
      pathogen virulence, or the length of the infectious period. On the other hand, an
      immune system is costly since it absorbs resources that otherwise might be
      invested in increasing the host's fertility or longevity. In addition, an active
      immune system may be able to clear pathogens efficiently but at the same time may
      result in immunopathology. By means of a reproductive value approach, we show how
      to compare the costs and benefits of an immune system systematically and how to
      derive the evolutionarily stable level of immune function. We then apply these
      methods to various plausible scenarios. The analysis reveals that the
      relationship between the life span of an organism and the optimal level of
      investment in immune function is less straightforward than one might expect.
      First, the prevalence of infection is reduced to the lowest possible level only
      under special circumstances. Second, members of a long-lived species do not
      necessarily have to invest more in immune function than those of a short-lived
      species. In fact, the opposite may be true. Third, the outcome of evolution can
      be contingent on the initial conditions. Depending on its initial investment
      strategy, a population may evolve to a state where very much or almost nothing is
      invested in a costly immune system.

PMID- 14970929
TI  - When genes go to sleep: the population genetic consequences of seed dormancy and
      monocarpic perenniality.
AB  - In many annual plant populations, seeds may be dormant for several seasons before
      they germinate. Here, we investigate the consequences of both conditional
      (dispersed seeds cannot enter a dormant stage) and unconditional seed dormancy on
      the amount and the distribution of neutral genetic diversity within and among
      populations. We present joint demographic and population genetics models for
      single and subdivided populations and derive the effective size and population
      differentiation at both local and metapopulation scales. We suggest that a
      Wahlund effect is unlikely to result from age structure alone. Furthermore, the
      differentiation among populations is decreased by the presence of seed banks. We
      also extend these models to describe monocarpic (semelparous) perennial life
      cycle, where the nonreproductive stages are vegetative rosettes instead of
      dormant seeds. The main difference between the models relies in the way the
      density-dependent regulation is acting. The effective size of monocarpic
      perennial species may be less than the census number of individuals, and among
      population differentiation is always larger than in annual species. We discuss
      our results in the light of recent population genetics surveys of annual plants
      with seed banks.

PMID- 14970930
TI  - The influence of space in genetic-environmental relationships when environmental
      heterogeneity and seed dispersal occur at similar scale.
AB  - We tested the importance of microenvironmental topographic parameters as
      predictors of emmer wheat genetic variation using three classes of single-locus
      (or at most several-loci) genetic markers (allozymes, glutenins, and qualitative
      traits) and two classes of markers of polygenic inheritance (phenological and
      morphological traits). Canonical correspondence analysis (CCA) and redundancy
      analysis (RDA) detected a significant effect of spatially structured
      environmental variation on genetic differences between plants for allozymes,
      glutenins, and quantitative morphological and phenological traits. However, after
      removing a spatial component of variation in partial CCA and partial RDA, the
      relationship of the remaining environmental variation with these genetic markers
      could be explained by chance alone, allowing us to rule out microniche
      topographic specialization in emmer wheat. Topographic autocorrelation exhibited
      a certain degree of similarity with genetic marker autocorrelation, indicating
      similar scales of environmental heterogeneity and seed flow. The detected
      population genetic structure agrees with one expected under isolation by distance
      as a result of limited gene flow. A negative relationship of genetic similarity
      with the logarithm of distance between plants was detected for both molecular
      markers and quantitative traits, which differed in the strength but not the
      pattern of association.

PMID- 14970931
TI  - Reduced-intensity conditioning or nonmyeloablative stem cell transplantation:
      introduction, rationale, and historic background.

PMID- 14970932
TI  - Nonmyeloablative stem cell transplantation: reduced-intensity conditioning for
      cancer immunotherapy--from bench to patient bedside.
AB  - Despite major progress in treating hematologic malignancies and, to a lesser
      extent, metastatic solid tumors, much work remains ahead. With the anticancer
      potential of immunotherapy not yet fully exploited, patients with leukemia,
      malignant lymphoma, and other hematologic malignancies for which high-dose
      chemoradiotherapy is frequently recommended in conjunction with stem cell
      transplantation (SCT) can now benefit from the advantages of immunotherapy
      mediated by cytokines or alloreactive donor lymphocytes, while minimizing
      procedure-related toxicity and mortality. The feasibility of applying allogeneic
      cell-mediated immunotherapy in conjunction with allogeneic SCT following reduced
      intensity conditioning, with minimal toxicity and no serious transplant-related
      complications, makes it possible to undertake such procedures on an outpatient
      basis as well as to offer an option for cure to elderly individuals and patients
      with less than optimal performance status. Being well tolerated, reduced
      intensity transplants also offer a chance for cure to patients with otherwise
      resistant leukemia and malignant lymphoma who have relapsed after autologous SCT.
      Thus, the traditional obstacle of very high transplant-related toxicity and
      mortality due to multiorgan failure from cumulative toxicity of multiple
      anticancer agents and radiation therapy is overcome. Although immunotherapy
      mediated by allogeneic lymphocytes can be most effective, the immune potential of
      donor lymphocytes should be maximized by nonspecific or specific activation in
      vitro or in vivo, or both, for more effective eradication of resistant tumor
      cells, including in patients with bulky disease. More important is the challenge
      to target donor lymphocytes to the tumor and minimize their capacity to induce
      responses against normal host tissues, which frequently results in severe acute
      and chronic graft-versus-host disease (GVHD). Alternatively, donor lymphocytes
      should be eliminated as soon as tumor eradication is completed, or as soon as
      severe GVHD becomes prohibitive. Based on available experience, clinical
      application of innovative therapy, especially at the stage of minimal residual
      disease (MRD), may open new horizons for the treatment of malignancies considered
      until recently to be incurable. The feasibility of controlling cancer by targeted
      chemotherapy, best illustrated by the phenomenal activity of imatinib in patients
      with chronic myelogenous leukemia and, more recently, in gastrointestinal stromal
      tumors (including in patients fully resistant to all known anticancer agents)
      suggests that in the future, tumor-specific chemotherapy may represent the
      ultimate goal for achieving a stage of MRD with minimal multiorgan toxicity.
      Together, the combination of immunotherapy and targeted chemotherapy may provide
      the most logical approach for making real progress in controlling resistant
      hematologic malignancies and metastatic solid tumors.

PMID- 14970933
TI  - Nonmyeloablative stem cell transplantation for lymphoma.
AB  - High-dose chemotherapy and allogeneic stem cell transplantation is a potentially
      curative therapy for younger patients with non-Hodgkin's lymphoma (NHL). The
      benefits of this therapy, however, are largely offset by the high rate of
      treatment-related mortality, exceeding 40% in many studies. Risks increase with
      comorbidities, advanced age, histocompatibility, and disease-related prognostic
      factors. Given the potential efficacy of graft-versus-malignancy effects against
      many lymphoid malignancies, we evaluated an alternative strategy utilizing less
      toxic, nonmyeloablative conditioning regimens to allow engraftment of donor
      cells, and then exploit the graft-versus-lymphoma (GVL) effects of allogeneic
      transplantation as the primary therapy. This strategy involved fludarabine-based
      preparative regimens +/- high-dose rituximab, graft-versus-host disease (GVHD)
      prophylaxis for 6 months, and donor lymphocyte infusion (DLI) only for
      progressive or nonresponding disease. Results from these trials confirm the full
      potential on nonmyeloablative transplantation for patients with NHL.

PMID- 14970934
TI  - Allogeneic transplantation of hematopoietic stem cells after nonmyeloablative
      conditioning for Hodgkin's disease: indications and results.
AB  - A number of treatment options are available for patients with relapsed Hodgkin's
      disease (HD). Radiotherapy, salvage chemotherapy, high-dose therapy (HDT)
      followed by autologous transplantation, and classical or nonmyeloablative
      conditioning followed by allogeneic transplantation can all be effective in
      patients with relapsed HD. Patients with early relapse after modern first-line
      chemotherapy, as well as patients with primary progressive disease, will be
      candidates for innovative approaches including nonmyelablative stem cell
      transplant (NST). Although initial results with NST look promising, more time and
      structured study of both HD and NST will be necessary to ultimately define the
      role of NST in this disease.

PMID- 14970935
TI  - Nonmyeloablative reduced-intensity transplantation in multiple myeloma.
AB  - Reduced-intensity conditioning (RIC) allogeneic transplants are being performed
      more frequently in a variety of hematologic malignancies. The aim is to exploit
      the graft-versus-tumor (GVT) effect seen after allografting without the
      toxicities of myeloablative conditioning. RIC regimens are being extensively
      explored for salvage therapy of myeloma. Although nonrelapse mortality rates are
      acceptable, relapse remains the most common cause of treatment failure. New
      combinations and novel therapies need to be explored to improve outcomes. This
      strategy should also be employed earlier in the course of the disease.

PMID- 14970936
TI  - Adoptive immunotherapy with antigen-specific T cells in myeloma: a model of tumor
      specific donor lymphocyte infusion.
AB  - Although partial remissions rates of up to 60% are obtained with conventional
      therapeutic regimens, multiple myeloma is essentially an incurable disease with a
      median survival of approximately 30 months. Allogeneic stem cell transplantation
      (SCT) results in a high percentage of complete remissions (CRs), but it can be
      associated with significant treatment-related mortality. Recent clinical studies
      have shown that highly immunosuppressive, yet nonmyeloablative, doses of
      fludarabine-based chemotherapy can result in alloengraftment. However, even with
      a reduction in treatment-related mortality, success with allogeneic SCT is
      limited by the significant risk of relapse. The goal of the strategy described is
      to transfer tumor antigen-specific immunity induced in the stem cell donor to the
      allogeneic SCT recipient to reduce relapse. Donors are immunized with a well
      defined vaccine, specific for the patient's tumor. The allogeneic SCT is
      performed with a conditioning regimen consisting of cyclophosphamide and
      fludarabine, and the stem cell source is blood mobilized with filgrastim, which
      could potentially enhance the transfer of a larger number of tumor-specific T
      cells in the allograft, as compared to bone marrow. Donor immunization with
      myeloma idiotype protein in the setting of a nonmyeloablative SCT may represent a
      novel strategy for the treatment of myeloma.

PMID- 14970937
TI  - Allogeneic stem cell transplantation as immunotherapy for nonhematological
      cancers.
AB  - Over the past two decades biologic therapy has played an increasing role in the
      treatment of cancer. While this field is still early in its development, there
      now exists compelling evidence that the immune system is capable of detecting and
      eliminating cancer cells. Although the majority of immunotherapy approaches for
      metastatic cancer involve strategies designed to enhance autologous immunity,
      most would agree that the graft-versus-leukemia reaction induced following
      allogeneic stem cell transplantation represents modern day's most potent form of
      cancer immunotherapy. While allogeneic stem cell transplantation has gained
      recognition as a potentially curative "immunotherapy" for a growing number of
      different hematological malignancies, its efficacy in inducing antimalignancy
      effects against nonhematological cancers has only recently begun to be
      investigated. The historical basis, development, and preliminary clinical results
      of allogeneic stem cell transplantation as a form of immunotherapy for treatment
      refractory solid tumors are reviewed.

PMID- 14970938
TI  - Immunoablative reduced-intensity stem cell transplantation: potential role of
      donor Th2 and Tc2 cells.
AB  - Allogeneic reduced-intensity stem cell transplantation (RISCT) decreases regimen
      associated morbidity and mortality, but it is unfortunately still constrained by
      the same immune T-cell reactions that limit myeloablative transplantation,
      including graft rejection, graft-versus-host disease (GVHD), and suboptimal graft
      versus-leukemia (GVL) or graft-versus-tumor (GVT) effects. Graft rejection is
      mediated by host T cells, whereas GVHD and GVL/GVT effects are initiated by donor
      T cells, and to this extent, future advances in RISCT will likely benefit from an
      ability to modulate both donor and host T-cell immunity. As a step in this
      direction, we have developed a RISCT approach that first involves chemotherapy
      induced host T-cell ablation, and second involves administration of allogeneic
      inocula enriched for donor CD4(+) Th2 and CD8(+) Tc2 T-cell subsets that in
      murine studies mediate reduced GVHD. In a pilot clinical trial, "immunoablative"
      RISCT with human leukocyte antigen (HLA)-matched related allografts resulted in
      rapid and complete donor chimerism and GVL effects early post-transplant, with
      GVHD being the primary toxicity. Using this immunoablative RISCT approach, we are
      now evaluating the feasibility and safety of augmenting allografts with
      additional donor CD4(+) Th2 cells that are generated in vitro via CD3/CD28
      costimulation in the presence of interleukin (IL)-4. We review the biology of
      host and donor T-cell immunity during allogeneic RISCT and discuss the strategies
      of host immunoablation and donor Th2 and Tc2 cell therapy as potential means to
      improve the clinical results in RISCT.

PMID- 14970939
TI  - Targeted cancer therapy and immunosuppression using radiolabeled monoclonal
      antibodies.
AB  - Radioimmunotherapy (RIT) as a means to target radiation therapy to tumor cells or
      to specifically suppress host immunity specifically in the setting of allogeneic
      transplantation is a promising new strategy in the armory of today's oncologist.
      Different approaches of RIT such as injection of a stable radioimmunoconjugate or
      the use of pretargeting are available. The choice of the radionuclide used for
      RIT depends on its radiation characteristics with respect to the malignancy or
      cells targeted. beta-Emitters with their lower energy and longer path length are
      more suitable for targeting bulky, solid tumors, whereas alpha-emitters with
      their high linear energy transfer and short path length are better suited to
      target cells or tumors of the hematologic system. Encouraging results have been
      obtained using these approaches treating patients with hematologic malignancies.
      While the results in solid tumors are somewhat less favorable, new strategies for
      patients with minimal residual disease (MRD), using adjuvant and locoregional
      treatment, are currently being investigated. In this report, we outline basic
      principles of RIT, give an overview of available radioimmunoconjugates and their
      clinical applications with special emphasis on their use in hematologic
      malignancies, including use in conditioning regimens for stem cell
      transplantation (SCT).

PMID- 14970940
TI  - The role of monoclonal antibodies in stem cell transplantation.
AB  - Monoclonal antibodies directed at the lymphoid antigens have become established
      treatments for hematological malignancies either alone or in combination with
      chemotherapy. However, their incorporation in the transplant setting remains
      investigational. This review focuses on the currently available data for in vitro
      and in vivo purging with these antibodies as well as their role in modulating
      graft-versus-host disease (GVHD).

PMID- 14970941
TI  - Apoptosis in cancer--implications for therapy.
AB  - Resistance towards apoptosis is a key factor for the survival of a malignant
      cell. Cancer results if there is too little apoptosis and cells grow faster and
      live longer than normal cells. In addition, defects in apoptosis signaling
      contribute to drug resistance of tumor cells. Thus, one of the main goals for
      oncologic treatment is to overcome resistance of tumor cells towards apoptosis.
      The exciting challenge in oncology is to translate the growing knowledge of
      apoptotic pathways into clinical applications. In this review we address the role
      of apoptosis signaling in tumorigenesis and drug resistance of tumor cells and
      discuss therapeutic approaches interfering with apoptosis pathways.

PMID- 14970960
TI  - Trial of amitriptyline for relief of pain in amputees: results of a randomized
      controlled study.
AB  - OBJECTIVE: To evaluate whether amitriptyline is more effective than placebo in
      improving phantom limb pain or residual limb pain. DESIGN: Randomized controlled
      trial of amitriptyline for 6 weeks. SETTING: University hospital. PARTICIPANTS:
      Thirty-nine persons with amputation-related pain lasting more than 6 months.
      INTERVENTION: Six-week trial of amitriptyline (titrated up to 125 mg/d) or an
      active placebo (benztropine mesylate). MAIN OUTCOME MEASURES: Analyses were
      conducted to examine whether there was a medication group effect on the primary
      outcomes (average pain intensity) and secondary outcome measures (disability,
      satisfaction with life, handicap). RESULTS: No significant differences were found
      between the treatment groups in outcome variables when controlling for initial
      pain scores. CONCLUSIONS: Our findings do not support the use of amitriptyline in
      the treatment of postamputation pain.

PMID- 14970961
TI  - Outcome of surgical release among diabetics with carpal tunnel syndrome.
AB  - OBJECTIVE: To compare the results of surgical decompression of carpal tunnel
      syndrome (CTS) in patients with diabetes with those of patients with idiopathic
      CTS. DESIGN: Prospective case series. SETTING: Ambulatory care in Italy.
      PARTICIPANTS: Twenty-four consecutive patients with diabetes type 1 or 2 and CTS
      (mean age, 66.7 y) were matched for age and sex with 72 patients (mean age, 66.2
      y) with idiopathic CTS. INTERVENTIONS: All patients underwent surgical release of
      CTS by the mini-incision of palm technique. MAIN OUTCOME MEASURES: Clinical and
      electrophysiologic evaluation and patient self-administered Boston Questionnaire
      (BQ) for the assessment of severity of CTS symptoms and hand functional status
      before and 1 and 6 months after surgery. RESULTS: After surgical release, almost
      all patients of both groups reported an absence of pain, disappearance or
      reduction of paresthesia, and improvement in hand function. One month after
      surgery, there was a significant improvement in clinical status, BQ scores, and
      distal conduction velocities of the median nerve. A further improvement was
      evident at 6-month follow-up. There were no differences between the 2 groups in
      the number of surgical complications, in clinical and electrophysiologic status,
      or in BQ scores before and after surgery. The improvement in distal conduction
      velocities of the median nerve, BQ scores, and clinical and electrophysiologic
      status were similar in the 2 groups after surgery. CONCLUSION: Diabetes is not a
      risk factor for poor outcome of surgical decompression of CTS. Patients with
      diabetes have the same probability of positive surgical outcome as patients with
      idiopathic CTS.

PMID- 14970962
TI  - Efficacy of modified constraint-induced movement therapy in chronic stroke: a
      single-blinded randomized controlled trial.
AB  - OBJECTIVE: To determine efficacy of a modified constraint-induced movement
      therapy (mCIMT) protocol for patients with chronic stroke. DESIGN: Multiple
      baseline, pre-post, single-blinded randomized controlled trial. SETTING:
      Outpatient clinic. PARTICIPANTS: Seventeen patients who experienced stroke more
      than 1 year before study entry and who had upper-limb hemiparesis and learned
      nonuse. INTERVENTION: Seven patients participated in structured therapy sessions
      emphasizing more affected arm use in valued activities, 3 times a week for 10
      weeks. Their less affected arms were also restrained 5d/wk for 5 hours (mCIMT).
      Four patients received regular therapy with similar contact time to mCIMT. Six
      patients received no therapy (control). MAIN OUTCOME MEASURES: The Fugl-Meyer
      Assessment of Motor Recovery (FMA), Action Research Arm (ARA) Test, and Motor
      Activity Log (MAL). RESULTS: The mCIMT patients exhibited greater motor changes
      on the FMA and ARA (18.4, 11.4) than regular therapy (6.0, 7.1) or control (-2.9,
      -4.5). Statistical analyses showed significant differences in motor improvement
      on the FMA (F(2,12)=11.2, P=.002) and the ARA (F(2,12)=14.0, P=.001). Post hoc
      analyses showed that, when pretreatment motor differences are controlled, mCIMT
      resulted in substantially higher posttreatment FMA and ARA scores. Amount and
      quality of arm use, measured by the MAL, improved only in mCIMT patients.
      CONCLUSIONS: mCIMT may be an efficacious method of improving function and use of
      the more affected arms of chronic stroke patients. Findings further affirm that
      repeated, task-specific practice is critical to reacquisition of function,
      whereas practice schedule intensity is less critical.

PMID- 14970963
TI  - Prosthetic device provision to landmine survivors in Bosnia and Herzegovina:
      outcomes in 3 ethnic groups.
AB  - OBJECTIVE: To determine differences in prosthetic provision, use, and
      effectiveness among unilateral lower-extremity amputees from 3 ethnic groups in
      Bosnia and Herzegovina. DESIGN: Case series with a consecutive sample of patients
      seen in field clinics. SETTING: Multiple field clinics in Bosnia and Herzegovina
      from October 1998 to May 2002. PARTICIPANTS: A total of 671 patients were
      examined, and information about their prosthetic history was recorded from
      observation or verbal responses. The majority of the amputations resulted from
      injuries inflicted by landmines. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Self-reported walking distance per day, prosthesis functionality
      (functional or nonfunctional as assessed by a physician and a prothetist),
      prosthesis status (broken or nonbroken as assessed by a physician and a
      prothetist), and employment status. RESULTS: Ethnic groups differed significantly
      in types of prostheses provided, functional status of the prostheses, and use of
      the prostheses for community ambulation. CONCLUSION: Prosthetic devices and
      delivery of rehabilitation services for unilateral lower-extremity amputees
      differed between ethnic groups. Despite these differences, functional prosthetic
      devices increased mobility. Persons in all 3 ethnic groups with functional
      prostheses were more mobile than persons with nonfunctional prostheses. The
      employment rate was higher for people with functional prostheses.

PMID- 14970964
TI  - Pharmacokinetics and safety of multiple oral doses of sustained-release 4
      aminopyridine (Fampridine-SR) in subjects with chronic, incomplete spinal cord
      injury.
AB  - OBJECTIVE: To examine the pharmacokinetics and safety of sustained-release 4
      aminopyridine (Fampridine-SR), a potassium channel blocker, in subjects with
      chronic, incomplete spinal cord injury (SCI). DESIGN: Open-label. SETTING:
      Clinical research unit in Ontario. PARTICIPANTS: Sixteen neurologically stable
      subjects with chronic, incomplete SCI (American Spinal Injury Association
      Impairment Scale grade B, C, or D). INTERVENTION: Oral administration of
      Fampridine-SR (25, 30, 35, 40, 50, 60 mg twice daily, each for 1 wk). MAIN
      OUTCOME MEASURES: Steady-state pharmacokinetic parameters: maximum observed
      plasma concentration (Cmax), minimum observed plasma concentration (Cmin),
      average observed plasma concentration (Cav), area under the plasma concentration
      time curve from 0 to 12 hours (AUC(0-12)), time to Cmax (tmax), plasma half-life
      (t(1/2)), apparent volume of distribution (Vd/F), and apparent total clearance
      (Cl/F). Safety assessments: physical examinations, vital sign measurements,
      clinical laboratory tests, electrocardiogram recordings, and adverse events.
      RESULTS: Mean steady-state Cmax, Cmin, Cav, and AUC(0-12) increased over the
      entire Fampridine-SR dosage range and were dosage dependent up to 50 mg twice
      daily. Fampridine-SR had a mean tmax of 2.2 to 3.0 hours and a mean t(1/2) of 5.7
      to 6.9 hours. Mean Vd/F (415.4-528.0 L) and Cl/F (51.4-57.7 L/h) were independent
      of dosage, as were mean tmax and t(1/2) across dosages. Adverse events were mild
      or moderate and were not dosage related. During the entire study period (17 wk),
      dizziness was the most frequently reported adverse event, followed by urinary
      tract infection, paresthesia, ataxia, and insomnia. CONCLUSION: In subjects with
      chronic, incomplete SCI, Fampridine-SR was slowly absorbed and eliminated, which
      will allow Fampridine-SR to be administered in a convenient twice-daily manner.
      Fampridine-SR was well tolerated at dosages from 25 to 60 mg twice daily.

PMID- 14970965
TI  - Prevalence of chronic pain and its impact on health-related quality of life in
      stroke survivors.
AB  - OBJECTIVES: To document the prevalence of chronic pain and to evaluate the effect
      of pain on quality of life (QOL) in patients 6 months or more after a stroke.
      DESIGN: Cross-sectional survey. SETTING: Outpatient clinic of a rehabilitation
      center. PARTICIPANTS: One hundred seven stroke patients (68 men, 39 women; mean
      age, 60.9 y) attending the outpatient clinic of a rehabilitation center.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients were interviewed
      on pain, QOL, mood, and functional status by using the short form of the Brief
      Pain Inventory (BPI), Medical Outcomes Study 36-Item Short-Form Health Survey (SF
      36), Beck Depression Inventory, and Modified Barthel Index (MBI), respectively.
      RESULTS: Self-reported chronic pain was present in 45 patients (42%), with 32
      having musculoskeletal pain and 13 central poststroke pain. It was significantly
      more common in patients with a shorter poststroke duration (P=.025), but was not
      related to the nature of stroke (infarct or bleed), age, gender, presence of
      depression, and MBI score. There was no difference in the SF-36 scores between
      patients with and without pain except for the domain of bodily pain. When
      compared with patients with musculoskeletal pain, patients with central
      poststroke pain were more likely to have sensory impairments (P=.009), higher
      pain scores on the question "least pain in the past 24 hours" of the BPI
      (P=.036), and lower scores on the vitality domain of the SF-36 (P=.042).
      CONCLUSION: Pain is common in chronic stroke patients, and it does not appear to
      have a significant effect on patients' QOL.

PMID- 14970966
TI  - Wheelchair skills training program: A randomized clinical trial of wheelchair
      users undergoing initial rehabilitation.
AB  - OBJECTIVE: To test the hypothesis that a brief, formalized period of additional
      wheelchair skills training is safe and results in significantly greater
      improvements in wheelchair skills performance than a standard rehabilitation
      program. DESIGN: Randomized controlled trial. SETTING: Rehabilitation center.
      PARTICIPANTS: Thirty-five wheelchair users (20 with musculoskeletal disorders, 15
      with neurologic disorders) admitted for initial rehabilitation. Subjects' mean
      age +/- standard deviation (SD) was 59+/-18.3 years. INTERVENTION: Subjects
      randomly allocated to the treatment group participated in the Wheelchair Skills
      Training Program (WSTP), averaging 4.5+/-1.5 training sessions, each 30 minutes
      long. Subjects in the control group did not receive any wheelchair skills
      training beyond that given in a typical rehabilitation stay. MAIN OUTCOME
      MEASURES: Wheelchair Skills Test (WST), version 2.4, before and after training.
      Changes in total percentage WST score and individual skill scores were examined.
      RESULTS: There were no adverse incidents. The control group's mean percentage
      score +/- SD increased from 60.1%+/-14.4% to 64.9%+/-13.3%, an 8% improvement of
      the posttest relative to the pretest (P=.01). The WSTP group's mean score
      increased from 64.9%+/-9.4% to 80.9%+/-5.6%, a 25% improvement of the posttest
      relative to the pretest (P<.000). The WSTP group showed significantly greater
      improvements than the control group (P<.000). Among the specific skills,
      significantly greater improvements were seen in the WSTP group for the gravel and
      high-curb descent skills (P<.001). CONCLUSIONS: The WSTP is safe and practical
      and has a clinically significant effect on the independent wheeled mobility of
      new wheelchair users. These findings have implications for the standards of care
      in rehabilitation programs.

PMID- 14970967
TI  - Inpatient rehabilitation of patients requiring hemodialysis.
AB  - OBJECTIVE: To evaluate the outcomes of patients who require hemodialysis and are
      admitted to an inpatient rehabilitation unit. DESIGN: Retrospective review of the
      data of all admissions to an inpatient rehabilitation unit in 2001. SETTING:
      University medical center. PARTICIPANTS: All inpatient rehabilitation admissions
      in 2001 (N=531), including 497 patients who did not require hemodialysis and 34
      who required hemodialysis. INTERVENTION: A comprehensive rehabilitation program
      including physical therapy and occupational therapy. Speech and language therapy
      and rehabilitation psychology were provided when necessary. MAIN OUTCOME
      MEASURES: Length of stay (LOS), change in total score on the FIM instrument, FIM
      efficiency, and place of discharge. RESULTS: Admission and discharge FIM scores
      of the patients requiring hemodialysis were virtually identical to those of the
      other patients admitted to the unit. The average LOS of the hemodialysis patients
      was 5.4 days longer than that of the other patients, and, therefore, efficiency
      scores of the dialysis group were less than those of the other patients. The rate
      of discharge to the community did not differ significantly for the dialysis
      group. CONCLUSIONS: Patients who require hemodialysis can benefit from
      rehabilitation services. Their improvement on the FIM instrument is comparable to
      that of other patients, but their LOS may be longer than that of other patients.

PMID- 14970968
TI  - Selective blocks of the motor nerve branches to the soleus and tibialis posterior
      muscles in the management of the spastic equinovarus foot.
AB  - OBJECTIVE: To identify the location of the motor nerve branches to the soleus and
      tibialis posterior muscles in relation to anatomic surface landmarks for
      selective motor nerve blocks in the management of the spastic equinovarus foot.
      DESIGN: Descriptive study by computed tomography (CT) scan of 12 hemiplegic legs.
      SETTING: Spasticity group at a university hospital. PARTICIPANTS: Twelve patients
      with hemiplegia (6 men, 6 women) with spastic equinovarus foot. INTERVENTION:
      Three-dimensional location of the motor nerve branches to the soleus and tibialis
      posterior muscles with CT scan, followed by selective motor branch blocks with
      anesthetics. MAIN OUTCOME MEASURES: Vertical, horizontal, and deep coordinates
      determined by CT scan in relation to anatomic surface landmarks (upper extremity
      of the fibula and vertical metallic element). Soleus and tibialis posterior
      spasticity (Ashworth Scale), soleus H-wave maximum (Hmax)/M-wave maximum (Mmax)
      ratio, and sensory testing before and after the blocks. RESULTS: The mean
      coordinates +/- standard deviation for the soleus motor branch were 10+/-5 mm
      (vertical), 17+/-9 mm (horizontal), and 30+/-4 mm (deep); for the tibialis
      posterior motor branch they were 45+/-6mm (vertical), 17+/-8mm (horizontal), and
      47+/-4 mm (deep). Spasticity and Hmax/Mmax ratio decreased after the blocks,
      confirming their efficiency. No subjects experienced additional sensory deficit.
      CONCLUSION: Our study determined the location of the motor nerve branches to the
      soleus and tibialis posterior muscles in relation to anatomic surface landmarks
      for selective motor branch blocks and neurolytic procedures. These coordinates
      allow us to perform selective motor blocks without CT scan.

PMID- 14970969
TI  - Relationship between regional bone density measurements and the time since injury
      in adults with spinal cord injuries.
AB  - OBJECTIVES: To determine the bone mineral density (BMD) of the legs, arms, and
      trunk region of a group of adults with spinal cord injury (SCI) and to determine
      the relationship between regional BMD values and the time since injury. DESIGN:
      BMD measurements were determined by total-body, dual-energy x-ray absorptiometry
      scans and percentage values (percentage-matched BMD), based on manufacturer
      supplied normative data for age, sex, body weight, and ethnic group. The
      relationship between percentage-matched BMD values and time since injury was
      determined by linear regression analyses. SETTING: Research laboratories in a
      university setting. PARTICIPANTS: Twenty-nine subjects (21 men, 8 women; mean
      age, 38.5 y) who had sustained an SCI a mean of 10.6 years earlier (range, 0.6
      35.3 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The relationship
      between percentage-matched BMD values and the time since injury. RESULTS: There
      was a significant inverse relationship between percentage-matched BMD leg (r2 = 
      .76), arm (r2 = -.45), and trunk (r2 = -.38) values and the log of time since
      injury. CONCLUSION: Despite the varying levels of SCI and other relevant BMD
      contributing factors, the regional percentage-matched BMD values were
      significantly inversely related to the log of time since injury.

PMID- 14970970
TI  - Comparison of ultrasonographic renal excursion to fluoroscopic diaphragmatic
      excursion for the assessment of diaphragmatic function in patients with high
      cervical cord injury.
AB  - OBJECTIVE: To compare the renal excursion detected by ultrasonography with the
      diaphragmatic excursion recorded by fluoroscopy in estimating the diaphragmatic
      function in patients with high cervical cord injury. DESIGN: Prospective, blinded
      comparative study. SETTING: A rehabilitation hospital affiliated with a medical
      university. PARTICIPANTS: Fifteen consecutively admitted patients with high
      cervical cord injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Chest
      radiographs, fluoroscopy of diaphragmatic motion, and ultrasonography of renal
      motion. RESULT: Of the 15 patients, 2 were diagnosed with hemidiaphragm paralysis
      using fluoroscopy and renal ultrasonography. The average diaphragmatic excursion
      was 59 mm (range, 30-83 mm) in 28 nonparalyzed hemidiaphragms. The average renal
      excursion was 49 mm (range, 28-61 mm). The correlation coefficient for
      fluoroscopic hemidiaphragm excursion and ultrasonographic renal excursion was
      .853. CONCLUSION: Ultrasonographic renal excursion and fluoroscopic diaphragmatic
      excursion correlated highly. With the fluoroscopy results as the criterion
      standard, the diagnostic sensitivity and specificity were both 100% for renal
      sonography. With the advantages of convenience of use, no radiation exposure, and
      high reproducibility, renal ultrasonography is recommended as a first-line
      screening and long-term follow-up tool for assessment of diaphragmatic function.

PMID- 14970971
TI  - Effect of bench height on sit-to-stand in children without disabilities and
      children with cerebral palsy.
AB  - OBJECTIVE: To evaluate the effect of seat height on sit-to-stand (STS) in
      children with cerebral palsy (CP) and in children without disabilities. DESIGN: A
      mixed design (subject type by seat height) with repeated measures for seat
      height. SETTING: Motion analysis laboratory. PARTICIPANTS: Ten children with mild
      CP (mean age, 10.9+/-2.7 y) and 10 children without disabilities (mean age, 8.7+/
      2.4 y). INTERVENTIONS: Kinematic and force measurements of STS were completed
      with 6 infrared cameras and 2 forceplates. MAIN OUTCOME MEASURES: Phase duration
      of the STS movement, amplitude and timing of ground reaction forces, and maximum
      head velocity during the movement. RESULTS: Children with CP took significantly
      longer to rise to standing (1.71 s) than children without disabilities (1.24 s)
      (F(1,18)=16.97). The extension phase of STS was also significantly longer for
      children with CP (.85 s) than for children without disabilities (.45 s)
      (F(1,18)=18.73). Seat height did not affect time to stand for either children
      with CP or children without disabilities (F(1,18)=2.82, P>.05). The duration of
      the extension phase, maximum horizontal and vertical velocity of the head, and
      maximum vertical ground reaction force were all significantly greater when
      children stood from the low bench height than from the higher bench height,
      although we found no significant differences by subject type for maximum
      horizontal and vertical head velocity or for maximum vertical ground reaction
      force. CONCLUSIONS: Although children with CP were able to modify their motor
      programs for STS to accommodate changes in seat height as readily as nondisabled
      children, the speed with which they extended against gravity was slower;
      therefore, the total STS movement took longer for them to complete than for
      children without disabilities. Because the time to complete STS from the low and
      high bench did not differ, it would appear that time to ascend from sitting may
      be invariant and therefore be a motor control parameter for the STS movement.

PMID- 14970972
TI  - Test-retest reliability of hand-held dynamometric strength testing in young
      people with cerebral palsy.
AB  - OBJECTIVE: To evaluate the test-retest reliability of measuring lower-limb
      strength with a hand-held dynamometer in young people with cerebral palsy (CP).
      DESIGN: One rater measured the isometric strength of the lower limbs in 10
      participants with CP on 2 occasions separated by 6 weeks. SETTING: University
      movement rehabilitation laboratory in Australia. PARTICIPANTS: Ten young people
      (mean age +/- standard deviation, 13.5+/-3.4 y) with spastic diplegic CP. Eight
      of the participants walked independently and 2 walked with assistive devices.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Retest reliability of lower
      limb strength, expressed in the units of measurement for the interpretation of
      group mean and individual scores and as intraclass correlation coefficients
      (ICC(2,1)). RESULTS: For groups, mean lower-limb strength increases of 7 kg (30%)
      could be interpreted as real change using 95% confidence intervals (CIs). For
      individuals, for strength gains to be interpreted as real change using 95% CIs,
      strength increases would need to be greater than 16.8 kg (70%) for the
      measurement of knee extension and to be greater than 4.3 kg (25%) for ankle
      plantarflexion. Measurement of hip extension strength was not reliable for group
      mean or individual scores. All reliability coefficients were greater than.80.
      CONCLUSION: A hand-held dynamometer can reliably measure changes in lower-limb
      strength for groups of young people with CP. It is uncertain whether this method
      is useful for evaluating change in individuals. Relying only on a coefficient of
      reliability to decide the usefulness of a measurement can be misleading.

PMID- 14970973
TI  - Effect of rocker soles on plantar pressures.
AB  - OBJECTIVE: To examine the effect of different types of rocker soles on plantar
      pressures. DESIGN: In-shoe plantar pressures were measured in subjects without
      deformity with baseline shoes and 3 types of rockers: toe-only, negative heel,
      and double. SETTING: Medical college. PARTICIPANTS: Forty healthy patients (20
      men, 20 women) without foot deformity. INTERVENTIONS: Plantar pressures were
      recorded over a 2 1/2-hour test period with over 400 steps analyzed for each type
      of rocker sole. Peak pressures, pressure-time integral (PTI), and sensor contact
      duration were computed for each step. MAIN OUTCOME MEASURES: Peak plantar
      pressure PTI, and contact duration were compared for each rocker with a baseline
      shoe. RESULTS: Significant reduction (P<.01) in peak pressure and PTI were
      recorded across the forefoot for all 3 rockers. The reduction of pressure at the
      forefoot was balanced by shifting pressure to the midfoot with the negative heel
      and toe-only rockers. CONCLUSION: This study lends scientific credence to the
      prescription of rocker soles for patients who need forefoot pressure reduction,
      such as in diabetic neuropathy and possible ulceration.

PMID- 14970974
TI  - Nontraumatic spinal cord injury rehabilitation: pressure ulcer patterns,
      prediction, and impact.
AB  - OBJECTIVE: To investigate the characteristics, predictors, and consequences of
      pressure ulcers in patients with nontraumatic spinal cord injury (SCI). DESIGN:
      Retrospective, 3-year, case series. SETTING: Tertiary medical unit specializing
      in SCI rehabilitation. PARTICIPANTS: Consecutive sample of 134 adult inpatient
      referrals with nontraumatic SCI. Patients requiring initial rehabilitation or
      readmission were included. INTERVENTION: Chart review. MAIN OUTCOME MEASURES:
      Primary outcome measures were presence of pressure ulcers on admission to
      rehabilitation, incidence of new pressure ulcers developing during
      hospitalization, and any complications attributable to pressure ulcers during
      inpatient rehabilitation. Secondary objectives were to examine the predictability
      of risk factors for pressure ulcers, to assess the usefulness of a model
      previously developed for predicting pressure ulcers in patients with chronic SCI,
      and to estimate the effect of pressure ulcers on rehabilitation of nontraumatic
      SCI. RESULTS: Prevalence of pressure ulcers among admissions was 31.3% (n=42).
      Only 2.2% (n=3) of patients developed a new pressure ulcer after admission. The
      length of stay (LOS) of patients admitted with a pressure ulcer was significantly
      longer than that of those without a pressure ulcer (geometric mean, 62.3 d for
      pressure ulcer vs 28.2 d for no pressure ulcer, P=.0001). Many previously
      identified risk factors for pressure ulcers in SCI patients did not apply to our
      nontraumatic SCI patients. It is estimated that the inpatient LOS for those
      patients with a significant pressure ulcer was increased by 42 days. CONCLUSIONS:
      Pressure ulcers are a common complication for people with nontraumatic SCI who
      are admitted for rehabilitation, and they have a significant impact on LOS.

PMID- 14970975
TI  - Sit-and-reach test can predict mobility of patients recovering from acute stroke.
AB  - OBJECTIVES: To establish the test-retest reliability of the sit-and-reach test
      (SRT) and to determine the capacity of the SRT to predict mobility of patients
      recovering from acute stroke. DESIGN: Study 1 consisted of repeating the SRT to
      examine its reliability over trials (same day) and sessions (alternate days).
      Study 2 consisted of measuring performance in the SRT 7 to 10 days poststroke and
      measuring mobility at discharge for prospective analysis. SETTING: Medical and
      rehabilitation wards in hospital in Hong Kong. PARTICIPANTS: Thirty-six subjects
      with acute stroke (study 1, n=10; study 2, n=26). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Between 7 and 10 days of stroke onset, distance reached on
      the SRT was measured. Mobility at discharge was assessed using the transfer and
      locomotion scale of the FIM instrument (FIM mobility) and a timed walk test.
      RESULTS: The intertrial and intersession reliability of the SRT were rated good,
      with intraclass correlation coefficients of .98 and .79, respectively. Distance
      reached on the SRT correlated with the FIM mobility score on discharge (r=.572,
      P=.002) and the distance achieved on the timed walk test (r=.524, P=.006).
      Distance reached on the SRT accounted for 32.7% and 27.5% of the variance in the
      FIM mobility score at discharge and the distance achieved on the timed walk test,
      respectively. CONCLUSIONS: Performance in the SRT is reliable and can
      significantly predict the mobility of patients with acute stroke at discharge.

PMID- 14970976
TI  - Strapped versus unstrapped technique of the prone press-up for measurement of
      lumbar extension using a tape measure: differences in magnitude and reliability
      of measurements.
AB  - OBJECTIVES: To determine (1) the reliability of the prone press-up to measure
      lumbar extension using a strap and not using a strap to control pelvic movement
      in experienced clinicians and students and (2) if a difference exists between the
      magnitude of lumbar extension range of motion between the strapped and unstrapped
      condition. DESIGN: Prospective study. SETTING: Academic laboratory. PARTICIPANTS:
      Convenience sample of 63 unimpaired volunteers (mean age +/- standard deviation,
      25.95+/-5.75 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Lumbar
      extension was measured in the prone position by using a tape measure to measure
      the perpendicular distance of the sternal notch to the support surface while
      using a strap and not using a strap to control pelvic movement. All measurements
      were performed independently by 2 groups of examiners (1 experienced group, 1
      student group) and repeated to determine intrarater and interrater reliabilities.
      RESULTS: Intrarater and interrater reliability were good or excellent for all
      methods and all measurement group comparisons (intraclass correlation coefficient
      range, .82-.91). Additionally, the amount of lumbar extension, as measured by the
      prone press-up, during the strapped condition was significantly greater than with
      the unstrapped condition. CONCLUSION: Use of a tape measure while the subject
      performs a prone press-up appears to be a reliable method for the measurement of
      lumbar extension. This technique is reliable whether the examiner is experienced
      or inexperienced and whether or not the subject has the pelvis secured with a
      strap.

PMID- 14970977
TI  - Variable-ratio pushrim-activated power-assist wheelchair eases wheeling over a
      variety of terrains for elders.
AB  - OBJECTIVES: To test (1) whether a prototype variable-ratio pushrim-activated
      power-assist wheelchair would decrease effort and perceived exertion associated
      with wheeling and (2) whether the prototype would be acceptable to elders.
      DESIGN: Repeated-measures design. SETTING: Biomechanics laboratory. PARTICIPANTS:
      Eleven elderly wheelers (mean age +/- standard deviation, 70.7+/-7.8 y).
      INTERVENTIONS: Wheelers propelled their own wheelchairs and the prototype on a
      level surface, a carpet, and an incline. MAIN OUTCOME MEASURES: Surface
      electromyographic activity from upper limb and torso, heart rate, number of
      pushes, category-ratio scale of perceived exertion, and Consumer Assessment of
      Power Assist Wheelchairs. RESULTS: Compared with subjects' own manual
      wheelchairs, the prototype was associated with lower heart rate elevation
      (P<.0125), lower perceived exertion (P<.0125), and reduced electromyographic
      activity in 5 of 8 muscles. Of the 11 participants, 10 found the prototype to be
      "very easy" or "easy" to push on level and inclined surfaces; 9 gave that
      assessment on carpeted and inclined surfaces. Seven would "definitely" or
      "probably" trade their manual chairs for the power-assist chair if given the
      opportunity. Nine thought they would venture to new and different places in a
      power-assist wheelchair. Time and number of pushes to complete tasks did not
      differ significantly between chairs. CONCLUSIONS: The prototype reduced the
      effort associated with wheeling and was an acceptable alternative to manual
      wheelchairs. Further testing outside the laboratory is warranted.

PMID- 14970978
TI  - Submaximal exercise in persons with stroke: test-retest reliability and
      concurrent validity with maximal oxygen consumption.
AB  - OBJECTIVE: To establish the test-retest reliability and concurrent validity with
      maximum oxygen consumption (VO2max) for 3 submaximal exercise tests in persons
      with chronic stroke: (1) submaximal treadmill test, (2) submaximal cycle
      ergometer test, and (3) 6-minute walk test (6MWT). DESIGN: Prospective study
      using a convenience sample. SETTING: Free-standing tertiary rehabilitation
      center. PARTICIPANTS: A volunteer sample of 12 community-dwelling individuals who
      had a stroke with moderate motor deficits. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Heart rate, blood pressure, and oxygen consumption (VO2) were
      assessed during the exercise tests. RESULTS: Test-retest reliability was good to
      excellent for the exercise tests (maximal and submaximal tests). VO2 for all
      submaximal measures related to VO2max (r range, .66-.80). Neither the 6MWT
      distance, self-selected gait speed, nor hemodynamic measures related to VO2max.
      CONCLUSION: The VO2 measures of the submaximal exercise tests had excellent
      reliability and good concurrent validity with VO2max. Submaximal exercise tests
      may be a method by which to monitor the effects of interventions after a
      screening test (eg, symptom-limited graded exercise test, dobutamine stress
      echocardiograph).

PMID- 14970979
TI  - Effects of electric stimulation on C and A delta fiber-mediated thermal
      perception thresholds.
AB  - OBJECTIVE: To determine if interferential current (IFC) or transcutaneous
      electric nerve stimulation (TENS) alters C and A delta fiber-mediated thermal
      perception thresholds. DESIGN: Single-blind, randomized controlled trial.
      SETTING: Laboratory. PARTICIPANTS: One hundred forty healthy women volunteers
      (mean age +/- standard deviation, 20.6+/-2.7 y). INTERVENTIONS: Subjects were
      randomly and exclusively assigned to 1 of 7 groups (n=20 in each): 0, 5, and 100
      Hz of IFC; 5 and 100 Hz of TENS; placebo and control stimulation. Stimulation was
      applied through 2 electrodes placed over the median nerve. Warm sensation, cold
      sensation, hot pain, and cold pain perception thresholds were measured from the
      thenar eminence by using a quantitative sensory testing device and a method of
      limits algorithm. MAIN OUTCOME MEASURES: Warm sensation, cold sensation, hot
      pain, and cold pain thresholds (degrees C) before, during, and after stimulation.
      RESULTS: There was a statistically significant effect of time for all 4 thermal
      perception thresholds (separate 2-way analyses of variance with repeated
      measures, all P<.001). There were no statistically significant differences
      between experimental groups, nor any interaction effects (all P>.05).
      CONCLUSIONS: Neither IFC nor TENS altered C and A delta fiber-mediated thermal
      perception thresholds. The results suggest that any analgesic mechanisms with
      these modalities are likely to be complex.

PMID- 14970980
TI  - Tai Chi improves standing balance control under reduced or conflicting sensory
      conditions.
AB  - OBJECTIVE: To investigate the effects of long-term Tai Chi practice on balance
      control when healthy elderly Tai Chi practitioners stood under reduced or
      conflicting somatosensory, visual, and vestibular conditions, as compared with
      healthy elderly non-Tai Chi practitioners and young subjects. DESIGN: Cross
      sectional study. SETTING: University-based rehabilitation center in Hong Kong.
      PARTICIPANTS: Twenty elderly Tai Chi practitioners (mean experience +/- standard
      deviation, 7.2+/-7.2 y) were compared with 20 elderly non-Tai Chi practitioners
      and 20 young, healthy university students. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: The amplitude of anteroposterior body sway under different
      somatosensory, visual, and vestibular conditions was measured using computerized
      dynamic posturography, whereby subjects underwent 6 combinations of visual and
      support surface conditions. RESULTS: The Tai Chi practitioners had significantly
      better balance control than the non-Tai Chi subjects in the visual and vestibular
      ratios, but not in the somatosensory ratio. Furthermore, there were no
      significant differences in any of these 3 sensory ratios when the Tai Chi
      practitioners were compared with those of the young, healthy subjects.
      CONCLUSIONS: Long-term Tai Chi practice improved balance control in the elderly
      population when there was an increased reliance on the visual and vestibular
      systems during stance. Of particular interest is that our elderly Tai Chi
      practitioners attained the same level of balance control performance as did
      young, healthy subjects when standing under reduced or conflicting somatosensory,
      visual, and vestibular conditions.

PMID- 14970981
TI  - The accuracy of ultrasonic estimation of bladder volume: a comparison of portable
      and stationary equipment.
AB  - OBJECTIVE: To compare the accuracy of portable and stationary ultrasonography
      equipment in estimating residual bladder volume. DESIGN: A prospective study.
      SETTING: A rehabilitation hospital affiliated with a medical university in
      Taiwan. PARTICIPANTS: Sixty-four patients with voiding dysfunction.
      INTERVENTIONS: Each patient received both types of ultrasonography, plus
      catheterization (as the criterion standard for measuring bladder volume). MAIN
      OUTCOME MEASURES: The mean errors and mean percentage error resulting from use of
      the 2 types of equipment were recorded. RESULTS: Stationary real-time
      ultrasonography had a lower absolute error (21.9+/-25.0 mL vs 34.4+/-38.2 mL) and
      percentage error (13.1%+/-10.5% vs 36%+/-52.4%) than the portable ultrasonography
      (P<.05). CONCLUSION: Stationary ultrasonography provided a more accurate estimate
      of residual bladder volumes than did the portable device. However, portable
      ultrasonography is more convenient to use and has an acceptable accuracy for
      clinical use.

PMID- 14970982
TI  - Can Tai Chi improve vestibulopathic postural control?
AB  - OBJECTIVES: To evaluate the rationale and scientific support for Tai Chi as an
      intervention for vestibulopathy and to offer recommendations for future studies.
      DATA SOURCES: A computer-aided search, including MEDLINE and Science Citation
      Index, to identify original Tai Chi studies published in English; relevant
      references cited in the retrieved articles were also included. STUDY SELECTION: A
      preliminary screening selected all randomized controlled trials (RCTs), non-RCTs,
      case-control studies, and case series that included Tai Chi as an intervention
      and had at least 1 outcome variable relevant to postural stability. DATA
      EXTRACTION: Authors critically reviewed studies and summarized study designs and
      outcomes in a summary table. DATA SYNTHESIS: Twenty-four Tai Chi studies met
      screening criteria. No studies specifically studying Tai Chi for vestibulopathy
      were found. Collectively, the 24 studies provide sometimes contradictory but
      generally supportive evidence that Tai Chi may have beneficial effects for
      balance and postural impairments, especially those associated with aging. Ten
      RCTs were found, of which 8 provide support that Tai Chi practiced alone, or in
      combination with other therapies, can reduce risk of falls, and/or impact factors
      associated with postural control, including improved balance and dynamic
      stability, increased musculoskeletal strength and flexibility, improved
      performance of activities of daily living (ADLs), reduced fear of falling, and
      general improvement in psychologic well-being. Studies using other designs
      support the results observed in RCTs. CONCLUSIONS: At present, few data exist to
      support the contention that Tai Chi specifically targets the impairments,
      functional limitations, disability, and quality of life associated with
      peripheral vestibulopathy. There are, however, compelling reasons to further
      investigate Tai Chi for vestibulopathy, in part because Tai Chi appears useful
      for a variety of nonvestibulopathy etiologic balance disorders, and is safe.
      Especially needed are studies that integrate measures of balance relevant to ADLs
      with other psychologic and cognitive measures; these might help identify specific
      mechanisms whereby Tai Chi can remedy balance disorders.

PMID- 14970983
TI  - Fibrocartilaginous embolism--an uncommon cause of spinal cord infarction: a case
      report and review of the literature.
AB  - Fibrocartilaginous embolism is a rare cause of spinal cord infarction. It is
      postulated that an acute vertical disk herniation of the nucleus pulposus
      material can lead to spinal cord infarction by a retrograde embolization to the
      central artery. An increased intradiskal pressure resulting from axial loading of
      the vertebral column with a concomitant Valsalva maneuver is thought to be the
      initiating event for the embolus. We present a previously healthy 16-year-old boy
      with sudden onset of back pain and progressive paraparesis within 36 hours after
      lifting exercises in a squat position. His clinical presentation and neuroimaging
      studies were consistent with spinal cord infarction resulting from a central
      artery embolus at the T8 spinal cord level. Laboratory investigation showed no
      evidence of infectious, autoimmune, inflammatory, or neoplastic causes. Although
      no histologic confirmation was obtained, lack of evidence for other plausible
      diagnoses in the setting of his clinical presentation and in the magnetic
      resonance imaging findings made fibrocartilaginous embolism myelopathy the most
      likely diagnosis. We postulated that some cases of transverse myelitis might
      actually be fibrocartilaginous embolism, making it a more prevalent cause of an
      acute myelopathy than commonly recognized. Relevant literature and current
      theories regarding the pathogenesis of fibrocartilaginous embolism myelopathy are
      reviewed.

PMID- 14970984
TI  - Arnold-Chiari malformation with syrinx presenting as carpal tunnel syndrome: a
      case report.
AB  - A 26-year-old administrative assistant presented with 3 years of left-hand
      dysesthesia involving primarily the first 3 digits. Her symptoms increased at
      night and with keyboard use. Through 12 visits to primary and specialty care
      physicians over 3 years, she experienced minimal improvement with splints and
      moderate improvement with gabapentin. On presentation, careful questioning
      revealed an abrupt onset of symptoms 3 years previously, related to a 2-week
      episode of gastritis associated with recurrent emesis. Examination revealed a
      negative Tinel sign over the median nerve at the wrist, decreased left biceps
      reflex, positive Spurling test, and decreased sensation over the palmar and
      dorsal surfaces of the left hand in the C5-6 distribution. The atypical onset of
      symptoms, poor response to therapy, and physical findings suggested the
      possibility of a radicular or central neurologic etiology for the patient's hand
      numbness. Magnetic resonance imaging demonstrated a Chiari I malformation with a
      syrinx extending from C2 to T10, with the greatest diameter at C4. Neurosurgical
      decompression led to a decrease in symptoms. A meticulous history and physical
      examination should be performed on patients with presumed carpal tunnel syndrome
      with an atypical onset of symptoms or response to therapy.

PMID- 14970985
TI  - Coupling agents in therapeutic ultrasound: acoustic and thermal behavior.
AB  - OBJECTIVE: To compare transmissivity data and thermal behavior of 4 coupling
      media. DESIGN: Experimental. SETTING: Postgraduate rehabilitation program in
      Brazil. SPECIMENS: Four coupling media: gel, mineral oil, white petrolatum, and
      degassed water. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The
      transmission, attenuation, reflection coefficient, and acoustic impedance of gel,
      mineral oil, white petrolatum, and degassed water were measured with a density
      measurement cell. The temperature variation in the therapeutic ultrasound
      transducer was measured with a thermocouple. RESULTS: The transmissivity data
      showed that the water and gel presented the highest transmission coefficient, the
      lowest reflection, and an attenuation coefficient and acoustic impedance close to
      that of the skin. The thermal data revealed the highest heating in the transducer
      during the insonation with white petrolatum and mineral oil, resulting from the
      thermal conductivity features of each medium. CONCLUSIONS: Transmissivity data
      obtained showed that water and gel present the best acoustic features. In
      ultrasound therapy, with the direct contact technique using thin layers of
      coupling agents, any product may be used, because the effect of the attenuation
      coefficient does not play a significant role when layers are as thin as those
      used in this experiment.

PMID- 14970986
TI  - Induction of myogenin messenger ribonucleic acid in rat skeletal muscle after 1
      hour of passive repetitive stretching.
AB  - OBJECTIVE: To investigate the effect of repetitive passive stretch of living rat
      muscle on myogenin messenger ribonucleic acid (mRNA) expression. DESIGN: Case
      controlled study. SETTING: University laboratory. ANIMALS: Seventeen female 8
      week-old Wistar rats. INTERVENTIONS: Repetitive stretch (15 times/min) was
      performed manually on gastrocnemius muscle of anesthetized rats for 15, 30, and
      60 minutes. MAIN OUTCOME MEASURES: Total RNA was extracted, after the animals
      were killed, from the gastrocnemius muscle, and Northern blotting was performed
      using oligonucleotide complementary to myogenin. RESULTS: Repetitive stretch to
      gastrocnemius muscles of anesthetized rats for 1 hour induced a 21.5% increase in
      the expression of myogenin mRNA. CONCLUSIONS: Repetitive passive stretch of the
      rat skeletal muscle for 60 minutes induced the expression of myogenic
      transcription factor myogenin mRNA. These findings suggest the clinical utility
      of passive repetitive stretch to maintain muscle strength in patients who are
      unconscious or paralyzed.

PMID- 14970987
TI  - Disability, chronic condition, and iatrogenic illness.
AB  - People with disabilities and chronic conditions are disadvantaged by the US
      health care system. Some people receive too few of the services they need; others
      receive too many services from practitioners who do not understand their
      disability-related needs and thus subject them to iatrogenic illnesses (health
      problems arising from the health care process). We explore this deprivation and
      excess and focus on 3 categories of iatrogenic illness that can harm this patient
      population and impede their ability to live independently. Empirical studies of
      iatrogenic illness in people with disabilities and chronic illnesses are needed.
      Physiatrists must play a central role in conducting such studies and in helping
      these persons access needed care while avoiding potential health problems
      associated with such care.

PMID- 14970989
TI  - Stuart Campbell's child comes of age.

PMID- 14970990
TI  - Gender-specific fetal biometry standards.

PMID- 14970991
TI  - Surveillance and outcome of fetuses with gastroschisis.
AB  - OBJECTIVES: Infants with gastroschisis have a high survival rate. However, the
      rate (10-15%) of intrauterine fetal death (IUFD) is considerable, and the
      association with fetal distress is well known. The aim of this study was to
      describe the outcome of fetuses with a prenatal diagnosis of gastroschisis. The
      impact of correct prenatal diagnosis, surveillance and signs of complicating risk
      factors were evaluated. METHODS: All fetuses with prenatally diagnosed
      gastroschisis at the National Center for Fetal Medicine from January 1988 to
      August 2002 were registered and prospectively evaluated with regular ultrasound
      examinations. From 34-36 completed gestational weeks the fetuses were monitored
      daily to every second day with cardiotocography (CTG). RESULTS: Gastroschisis was
      diagnosed in 64 fetuses at a mean gestational age of 19 + 2 weeks. All had normal
      karyotype. Associated anomalies were found in four cases (6.3%). Three
      pregnancies (4.7%) were terminated, all for reasons other than gastroschisis. One
      fetus (1.6%) died in utero. Thirteen fetuses (22%) had abnormal CTG leading to
      subsequent Cesarean sections. Mean gestational age at delivery was 36 + 1 weeks.
      Mean birth weight was 2586 g. Thirteen infants (22%) were small for gestational
      age (SGA). In 15 cases (25%) meconium-stained amniotic fluid was found; 14 of
      these had abnormal CTG and/or were SGA. Small bowel atresia was found in four
      infants (6.7%). Four infants died postnatally at the age of 0-9 months.
      CONCLUSIONS: CTG surveillance of fetuses with gastroschisis may improve the
      outcome through detection of fetal distress thereby reducing the risk of IUFD.
      Other clinical situations of importance that are associated with gastroschisis
      are described and discussed.

PMID- 14970992
TI  - Width of the fetal lateral ventricular atrium between 10 and 12 mm: a simple
      variation of the norm?
AB  - OBJECTIVES: The prognosis of borderline forms of anomalies that can be detected
      by ultrasound is one of the most challenging issues in prenatal diagnosis. The
      aim of this study was to determine the prognosis for fetuses presenting with
      isolated mild ventriculomegaly (MVM). METHODS: Fetuses in which the width of the
      lateral ventricular atria was 10-12 mm and which had no other detectable
      chromosomal or morphological anomalies were followed by monthly ultrasound
      examinations until delivery. For the cases identified up to December 1997,
      postnatal information was gathered retrospectively through interviews. Children
      born from January 1998 onwards were included in a protocol involving planned
      neuropsychiatric visits at 12 and 18 months of age in which the Griffith scale
      was used to assess neurodevelopment. RESULTS: Between September 1992 and January
      2001, 60 fetuses with isolated MVM were identified. Ventricular dilatation
      diminished in 18 cases (and became normal in nine of these) and stabilized in 42
      cases. Information was obtained on 38 children born up to December 1997 and their
      neurodevelopment was found to be completely normal. The 22 children born from
      January 1998 onwards showed normal development at 12 and 18 months of age.
      CONCLUSIONS: When MVM is observed on prenatal ultrasound examination it can be
      very difficult to offer parents appropriate counseling. It is important to
      exclude aneuploidy or morphological abnormalities but even then there will be
      anxieties about long-term neurological outcome. Our data, which show normal
      neurodevelopment between 18 months and 10 years after birth in cases of MVM (10
      12 mm), should provide a basis for reassuring counseling.

PMID- 14970993
TI  - Fetal heart rate and blood flow velocity variability in the presence of increased
      nuchal translucency: a preliminary study.
AB  - OBJECTIVE: To study the power spectrum distribution of heart rate and umbilical
      artery flow velocity variability in fetuses with increased nuchal translucency
      thickness (NT). METHODS: Doppler velocity waveforms were collected from long
      lasting (>20 s) umbilical artery recordings in 18 fetuses with increased NT (>3
      mm) and 18 normal controls matched for gestational age at 11-14 (median, 12)
      weeks. The NT group included 11 abnormal karyotypes: trisomy 18 (n = 3), 45,X (n
      = 4), trisomy 21 (n = 3) and a balanced translocation. Absolute heart rate as
      well as the coefficient of variation for both beat-to-beat heart rate variability
      and umbilical artery blood flow velocity variability were determined. The ratios
      of the integrated low-frequency components (0.05-0.2 Hz) and the integrated high
      frequency ones (0.25-1.6 Hz; LH ratio) from normalized power spectrum
      distributions were established to reflect sympathovagal balance. RESULTS: The
      mean heart rate was not significantly different between the two groups. However,
      mean heart rate variability and time-averaged flow velocity variability were
      significantly increased in the NT group, while there was no significant
      difference in the LH ratios between the two groups. The mean umbilical artery
      pulsatility index was significantly higher in the NT group. CONCLUSION: The
      autonomic nervous system does not seem to play a role in the altered
      cardiovascular homeostasis in the presence of increased fetal NT.

PMID- 14970994
TI  - Sex-specific antenatal reference growth charts for uncomplicated singleton
      pregnancies at 15-40 weeks of gestation.
AB  - OBJECTIVE: Female fetuses, on average, weigh less than male fetuses at all
      gestational ages. The purpose of this study was to compare female and male
      fetuses in terms of intrauterine ultrasound growth measurements and to develop
      gestational-age-related charts based on a computerized perinatal database.
      METHODS: This was a retrospective study of unselected women in the second and
      third trimesters of pregnancy, who had a normal scan at 10-14 weeks. Data
      analysis was performed using measurements obtained from a mixed-race population
      of 4234 women, who underwent 5198 ultrasound examinations. The scans were
      performed by four trained sonographers, according to a standardized protocol.
      Routine measurements included biparietal diameter (BPD), head circumference (HC),
      abdominal circumference (AC) and femur length (FL). The main end-points were sex-
      and race-specific differences in fetal biometry, which were also used to estimate
      fetal weight. RESULTS: The base-line demographic characteristics and risk factors
      were comparable in female and male fetuses. Significant differences in fetal BPD,
      HC, AC and estimated fetal weight, but not FL, were seen between male and female
      fetuses. Centile charts for each of these variables were constructed for both
      male and female fetuses. CONCLUSIONS: This study suggests that small but
      consistent sex-related differences in prenatal BPD, HC and AC measurements are
      established by as early as 15 weeks of gestation. The use of sex-specific
      nomograms may improve the prenatal assessment of fetal growth as well as the
      diagnosis of structural abnormalities.

PMID- 14970995
TI  - Sex-specific fetal weight prediction by ultrasound.
AB  - OBJECTIVE: To improve sonographic birth-weight prediction by developing fetal
      gender-specific formulae. METHODS: This was a retrospective cross-sectional
      study. Two gender-specific formulae were produced from the data of 527 patients
      and the data of a further 349 patients were used to evaluate the formulae.
      Inclusion criteria were a singleton live fetus, gestational age above 25 weeks,
      birth weight between 1000 g and 4500 g and fetal biometry within 8 days of
      delivery. Data retrieval was specifically for the purpose of this study. RESULTS:
      To yield the best-fit weight formula for each fetal gender we employed step-wise
      regression analysis based on fractional polynomials with the biometric parameters
      biparietal diameter (BPD), head circumference (HC), transverse abdominal diameter
      (TAD), abdominal circumference (AC) and femur length (FL): estimated fetal weight
      for girls (g) = - 4035.275 + 1.143 x BPD3 + 1159.878 x AC1/2 + 10.079 x FL3 -
      81.277 x FL2 [in cm]; estimated fetal weight for boys (g) = 43576.579 + 1913.853
      x log10BPD + 0.01323 x HC3 + 55.532 x AC2 - 13602.664 x AC1/2 - 0.721 x AC3 +
      2.31 x FL3 [in cm]. These formulae showed superior results compared with those of
      conventional weight formulae. CONCLUSION: Gender-related fetal weight calculation
      allows optimized prediction of fetal weight at birth.

PMID- 14970996
TI  - Determining zygosity in early pregnancy by ultrasound.
AB  - OBJECTIVES: First-trimester ultrasound can reliably determine chorionicity but
      not zygosity. We set out to investigate whether it may be possible to determine
      zygosity using ultrasound by noting the number of corpora lutea (CLs), structures
      which reflect ovulation. In the presence of a dichorionic twin pregnancy, the
      identification of one CL would suggest that twins are monozygotic whereas two CLs
      implies dizygosity. METHODS: This was a retrospective analysis of predominantly
      spontaneous twin pregnancies presenting for an early pregnancy ultrasound at 5-8
      completed weeks of gestation. Placentation was correlated with presumed zygosity
      as predicted by the number of CLs present. RESULTS: Of 33 twin gestations,
      chorionicity was compatible in all cases with the predicted zygosity. In 15 cases
      one CL was seen and these were designated monozygotic. Of these, four were of
      monochorionic placentation and 11 dichorionic. The remaining 18 cases had two CLs
      and were presumed dizygotic; all were of dichorionic placentation. CONCLUSION: We
      propose a novel technique of zygosity determination during very early pregnancy
      which may have implications both clinically and in genetic research involving
      twins. However, this study requires further verification by comparing ultrasound
      results with DNA evidence taken after birth.

PMID- 14970997
TI  - The cocoon sign: a potential sonographic pitfall in the diagnosis of twin - twin
      transfusion syndrome.
AB  - OBJECTIVES: To investigate the frequency and clinical importance of the cocoon
      sign in twin-twin transfusion syndrome (TTTS). METHODS: Charts and ultrasound
      images of all pregnancies with TTTS that underwent selective laser
      photocoagulation of communicating vessels at our institution over a 1-year period
      were retrospectively reviewed for a cocoon sign. TTTS had been diagnosed and
      prospectively staged if monochorionicity was suspected and the maximum vertical
      pocket (MVP) of amniotic fluid in one gestational sac was >/=8 cm, while the MVP
      in the other gestational sac was </=2 cm. The cocoon sign was diagnosed when
      there was an ultrasound finding of a donor twin with severe oligohydramnios
      enveloped by dividing membranes and connected to the uterine wall by a laminar
      stalk of these membranes. RESULTS: The cocoon sign was noted in 9/58 (15.5%)
      cases. There were no differences in gestational age and stage of TTTS upon
      presentation, gestational age at delivery or number of neonatal survivors between
      the groups of TTTS cases with and those without a cocoon sign. One patient in the
      cocoon group had been misdiagnosed because the donor twin's MVP was measured from
      the donor's tethered membranes to the posterior wall of the uterus within the
      recipient's sac. CONCLUSIONS: The cocoon sign is present in at least 15% of
      patients with TTTS. Its recognition is important to avoid misdiagnosis of TTTS.
      The practical implications and potential complications of this sonographic sign
      are discussed.

PMID- 14970998
TI  - Sonographic measurement of cervical length in twin pregnancies in threatened
      preterm labor.
AB  - OBJECTIVE: To determine whether sonographic measurement of cervical length in
      twin pregnancies presenting with threatened preterm labor helps distinguish
      between true and false labor. METHODS: In 87 women with twin pregnancies
      presenting with regular and painful uterine contractions at 24-36 (median, 30)
      weeks of gestation, cervical length was measured by transvaginal ultrasound.
      Women presenting in active labor, defined by the presence of cervical dilation of
      3 cm or more, with ruptured membranes and those who underwent a prior or
      subsequent cervical cerclage, were excluded from the study. The clinical
      management was determined by the attending obstetrician without taking into
      account the cervical length. Primary outcome of the study was delivery within 7
      days of presentation. RESULTS: Delivery within 7 days of presentation occurred in
      19/87 (22%) pregnancies and this was inversely related to cervical length,
      decreasing from 80% (4/5) at 1-5 mm, to 46% (6/13) at 6-10 mm, 29% (4/14) at 11
      15 mm, 21% (4/19) at 16-20 mm, 7% (1/15) at 21-25 mm and 0% (0/21) at >25 mm.
      Logistic regression analysis demonstrated that significant independent
      contribution in the prediction of delivery within 7 days was provided by cervical
      length (odds ratio (OR) = 0.78, 95% CI 0.68-0.89, P < 0.001) and use of
      tocolytics (OR = 0.13, 95% CI 0.02-0.76, P = 0.024), with no significant
      contribution from gestation at presentation, chorionicity, ethnic origin,
      maternal age, body mass index, parity, previous history of preterm delivery,
      cigarette smoking, contraction frequency, vaginal bleeding or the administration
      of antibiotics or steroids. CONCLUSION: In women with twin pregnancies presenting
      with threatened preterm labor, sonographic measurement of cervical length helps
      distinguish between those who deliver within 7 days and those who do not.

PMID- 14970999
TI  - Effect of parity on second-trimester uterine artery Doppler flow velocity and
      waveforms.
AB  - OBJECTIVES: To investigate the relationship between second-trimester uterine
      artery Doppler findings and parity in a large pregnant population. METHODS:
      Uterine artery Doppler studies were performed in all singleton pregnancies at 18
      23 weeks of gestation. The mean uterine artery resistance index and the presence
      or absence of protodiastolic notches were recorded. Two groups were identified:
      pregnancies not complicated by pre-eclampsia, and pregnancies with pre-eclampsia
      severe enough to require delivery at or before 32 weeks of gestation. RESULTS: In
      the 4132 pregnancies uncomplicated by pre-eclampsia, parity was shown to be an
      independent predictor for both mean uterine artery resistance index (beta =
      0.073, P < 0.001) and the presence of bilateral protodiastolic notches (odds
      ratio = 0.67; 95% CI, 0.45-0.98). In the 17 pregnancies complicated with severe
      pre-eclampsia, uterine artery Doppler indices showed a trend towards being better
      predictors of disease in nulliparous compared with parous women. CONCLUSION:
      Parity has a significant effect on the resistance index and the prevalence of
      protodiastolic notching in the uterine artery flow waveforms. This difference is
      clinically noticeable in its effect on notching. These findings suggest that some
      permanent modification may persist in the maternal vessels after a successful
      pregnancy, altering their impedance in subsequent pregnancies.

PMID- 14971000
TI  - The value of uterine artery Doppler in the prediction of uteroplacental
      complications in multiparous women.
AB  - OBJECTIVE: To investigate the value of second-trimester uterine artery Doppler in
      the prediction of complications resulting from uteroplacental insufficiency in
      low- and high-risk multiparous women. METHODS: Color flow pulsed Doppler imaging
      of both uterine arteries at 20 weeks' gestation was performed on 628 multiparous
      women; 458 of them had no known risk factors and 170 had clinically identifiable
      high-risk factors at booking. An abnormal result was defined as bilateral notches
      and a mean resistance index (RI) >/= 0.55 (50th centile) or unilateral notches
      and a mean RI >/= 0.65 (80th centile). The main outcome measure was adverse
      pregnancy outcome defined as any case of pre-eclampsia, small-for-gestational age
      birth weight (< 5th centile), placental abruption, stillbirth or early neonatal
      death. RESULTS: There was an adverse outcome in 30 women (6.6%) in the low-risk
      group and 48 (28.2%) women in the high-risk group. In the high-risk group the
      sensitivity to predict adverse pregnancy outcome in screen-positive women was
      81.4% for a specificity of 89.0%, a positive predictive value of 71.4% and a
      negative predictive value of 93.4%. Normal Doppler studies in the high-risk group
      conferred a risk of adverse perinatal outcome of 6.6%, similar to the risk of
      adverse outcome in the low-risk population (6.6%). In the low-risk group the
      sensitivity for an adverse outcome in screen-positive women was 33.3% for a
      specificity of 92.8% and a positive predictive value of 24.4%. CONCLUSION: In
      high-risk multiparous women, persistent bilateral notches with mean RI >/= 0.55
      and unilateral notches with mean RI >/= 0.65 at 20 weeks' gestation identifies
      the vast majority of women who will subsequently develop complications secondary
      to uteroplacental insufficiency. Normal uterine artery Doppler studies in these
      women confers a risk of adverse outcome similar to that of women with an
      uncomplicated obstetric history. In low-risk women, the screening efficacy of
      uterine artery Doppler for adverse perinatal outcome is poor and does not justify
      routine screening.

PMID- 14971001
TI  - What women want: women's preferences of caregiver behavior when prenatal
      sonography findings are abnormal.
AB  - OBJECTIVE: To determine what women value when receiving news of a pregnancy
      abnormality detected by ultrasound. METHODS: Women who had a pregnancy
      complication detected sonographically in the year 2000 were asked to complete a
      survey of 21 questions measuring the importance of various factors related to the
      receipt of bad news. Of the target sample of 117 women who agreed to participate,
      76 (64.9%) returned completed surveys. Cases included serious anomalies (67%) and
      soft markers/obstetric complications (33%). RESULTS: Responses to questions on
      'information quality', 'prompt provision of information', 'information-provider
      behavior' and 'information provision environment' showed that women attached the
      most importance to information quality, much more so than to promptness. Speed
      was even less important than information-provider empathy. Answers concerning use
      of the terms 'fetus' or 'baby' revealed greater variation in preferences than any
      other. Privacy was the most important environmental variable, more important than
      some information quality variables, or any promptness variable. Intervening
      variables considered included demographic variables and the seriousness of the
      prognosis. Education was the most useful predictor of preferences, with highly
      educated women generally placing less value on environment and some information
      quality variables, and having different preferences concerning the terms 'fetus'
      and 'baby'. CONCLUSIONS: Our findings shed some light on what is important to
      women who face bad news. Although more research is needed in this important area,
      we hope that our findings may assist institutions and caregivers in establishing
      guidelines for the effective and considerate communication of bad news.

PMID- 14971002
TI  - The value of detection of normal ovarian tissue (the 'ovarian crescent sign') in
      the differential diagnosis of adnexal masses.
AB  - OBJECTIVE: The aim of the study was to evaluate whether the presence of normal
      ovarian tissue adjacent to an adnexal tumor (the 'ovarian crescent sign') could
      assist in the preoperative differential diagnosis of adnexal lesions. METHODS:
      This was a prospective observational study including 100 women with a
      preoperative diagnosis of an adnexal mass. Demographic and biochemical data were
      collected and all women underwent a detailed transvaginal ultrasound scan. Tumor
      volume, morphological characteristics and Doppler features were recorded in each
      case. In addition, the tissue adjacent to the cyst was systematically examined
      for the presence of normal ovarian tissue. All the findings were compared to the
      final histological diagnosis. RESULTS: Sixty-seven (67%) of the cysts removed
      were benign, nine (9%) were borderline and 24 (24%) women had invasive malignant
      lesions. Normal ovarian tissue was seen in 58/76 (76%) women with non-invasive
      lesions, and in one woman (4%) with an invasive malignancy. In the absence of
      normal ovarian tissue, ovarian cancer was diagnosed with a sensitivity of 96% and
      specificity of 76%. CONCLUSION: The presence of normal ovarian tissue adjacent to
      an ovarian cyst is a useful morphological feature that may be used to help
      exclude an invasive ovarian malignancy in women with adnexal masses detected on
      ultrasound scan.

PMID- 14971003
TI  - Congenitally corrected transposition of the great arteries: clues for prenatal
      diagnosis.
AB  - Congenitally corrected transposition of the great arteries (ccTGA) is an uncommon
      cardiac defect characterized by the atria connecting with the anatomically
      discordant ventricles and the ventricles connecting with discordant and
      transposed great arteries. Parallel vessels are evident in corrected TGA, but as
      this sign is also present in complete TGA, a heart anomaly requiring major
      cardiac surgery in the postnatal period, it is important to differentiate between
      the entities prenatally. Most cases of ccTGA have associated anomalies but
      isolated forms or those with a mild associated cardiac anomaly are infrequently
      detected prenatally. We report on three cases detected between 21 and 25 weeks'
      gestation on screening ultrasound with associated mild findings. One fetus had an
      isolated ventricular septal defect (VSD) first detected at 34 weeks. The child
      developed heart block at 4 years of age. The second case was associated with a
      small VSD, a tiny pulmonary trunk and a persistent right umbilical vein. After
      birth, mild pulmonary stenosis was found as an additional cardiac finding at 4
      months of age. The third fetus had no additional cardiac anomalies prenatally,
      but after birth a bicuspid aortic valve was detected. The first case needed
      pacemaker implantation but the other two children required no cardiac surgery.
      Two of the cases were referred because abnormal vessel anatomy was detected on
      screening ultrasound. As prenatal detection of TGA is becoming a more frequent
      occurrence, this paper aims to present clues aiding in the prenatal diagnosis of
      atrioventricular and ventriculoarterial discordance, especially in its
      differentiation from complete transposition. These details are crucial for
      counseling and perinatal management.

PMID- 14971004
TI  - Caroli's disease: prenatal diagnosis, postnatal outcome and genetic analysis.
AB  - Caroli's disease is a rare autosomal recessive condition characterized by cystic
      dilatation of the intrahepatic bile ducts and infantile polycystic kidney
      disease. We report a case with Caroli's disease detected prenatally at 33 weeks'
      gestation with fetal ultrasound findings of a cystic liver mass and echogenic
      kidneys. Postnatal investigation confirmed enlarged and echogenic kidneys with
      dilatation of the intrahepatic bile ducts consistent with the diagnosis of
      Caroli's disease. Genetic analysis of the gene, PKHD1, associated with autosomal
      recessive polycystic kidney disease (ARPKD) showed that the patient had compound
      heterozygous mutations, confirming that this early onset Caroli's disease was
      part of the spectrum of ARPKD. To our knowledge this is the third case of
      Caroli's disease detected prenatally and the first in which the infant survived.

PMID- 14971005
TI  - Contrast-enhanced sonography during uterine artery embolization for the treatment
      of leiomyomas.
AB  - Uterine artery embolization (UAE) is a successful and safe treatment for
      symptomatic leiomyomas. However, rare complications such as premature menopause
      and uterine necrosis can arise because of embolization of non-target tissues. We
      studied the feasibility of using contrast-enhanced sonography with intravenous
      SonoVue just before, during and after complete occlusion of both uterine
      arteries. In a patient with multiple, large, symptomatic leiomyomas, contrast
      enhanced imaging established that the UAE was technically successful and that
      myometrial vascularity was not reduced. Our case suggests that ultrasound
      contrast agents may have a role in monitoring UAE and thus may help prevent
      ischemic complications. Further studies are required to confirm this.

PMID- 14971006
TI  - Ultrasound imaging of the pelvic floor. Part I: two-dimensional aspects.
AB  - Ultrasound imaging is rapidly replacing radiological methods in the investigation
      of pelvic floor disorders. Transrectal, transvaginal/introital and
      transperineal/translabial methods are being employed, with the latter probably
      the most widespread due to ease of use and availability of equipment. Position
      and mobility of the bladder neck, bladder wall thickness, pelvic floor muscle
      activity and uterovaginal prolapse can be quantified, and color Doppler may be
      used to document stress urinary incontinence. Ultrasound imaging has simplified
      audit activities and enhanced our understanding of the effects of incontinence
      and prolapse surgery, such as the new synthetic suburethral slings. In recent
      years, imaging methods have contributed significantly to our understanding of the
      traumatic effects of childbirth on the pelvic floor. Finally, the assessment of
      pelvic floor biomechanics may have implications for clinical obstetrics and
      ultimately for the prevention of delivery-related pelvic floor trauma.

PMID- 14971007
TI  - Prenatal diagnosis of choledochal cyst using ultrasound and magnetic resonance
      imaging.

PMID- 14971008
TI  - In-utero defecation between weeks 14 and 22 of gestation: stools are whitish.

PMID- 14971009
TI  - Nasal bone and trisomy 21: prenatal ultrasound and postmortem morphohistological
      study.

PMID- 14971010
TI  - Absent nasal bone: applying the right terminology and interpretation.

PMID- 14971012
TI  - Prenatal diagnosis of true knot of the umbilical cord.

PMID- 14971014
TI  - Broadband and band-selective IMPRESS-gHMBC: compensation of refocusing
      inefficiency with synchronized inversion sweep.
AB  - Compensation of refocusing inefficiency in a gHMBC experiment by replacing the
      rectangular pi pulse with a pair of adiabatic pulses with synchronized inversion
      sweep (CRISIS) significantly improves the performance of the gHMBC experiment.
      The CRISIS-gHMBC experiment retains the pure absorptive shapes in F1 and hence
      results in better lineshape and higher resolution than the current versions of
      magnitude mode gHMBC spectra. When used as a broadband experiment, CRISIS-gHMBC,
      owing to better refocusing efficiency of the adiabatic pulse pairs, gives
      improved performance across the 13C spectral width. Moreover, it is shown that
      CRISIS-gHMBC is a robust and improved alternative and when used along with the
      IMPRESS (Improved Resolution using Symmetrically Shifted pulses) technique
      further increases the sensitivity and resolution without additional experimental
      time. The IMPRESS-CRISIS combination is demonstrated for broadband gHMBC and band
      selective gHMBC experiments. The ICbs-gHMBC [IMPRESS-CRISIS-band-selective gHMBC]
      experiment is an attractive and better alternative to individual band-selective
      gHMBC.

PMID- 14971015
TI  - Gs-HSQC-NOESY versus gs-NOESY-HSQC experiments: signal attenuation due to
      diffusion; application to symmetrical molecules.
AB  - Gradient-selected (gs) HSQC-NOESY type experiments are often applied in order to
      obtain NOE cross peaks in symmetrical molecules or in complex organic molecules,
      e.g. carbohydrates. Since the coherence-selecting gradients in these pulse
      sequences are separated by several delays, including the mixing time, the gs-HSQC
      NOESY spectra exhibit severe signal attenuation due to diffusion effects. The
      respective NOE information unaffected by diffusion effects can be obtained by X
      half-filtered gs-NOESY-HSQC spectra. In this paper, an X-half-filtered version of
      the gs-NOESY-HSQC experiment is presented and the NOE cross peak integrals of its
      spectra are compared with those of a standard gs-HSQC-NOESY experiment. With
      phenanthrene as an example of symmetrical molecules, it is shown that the
      relative signal attenuation of gs-HSQC-NOESY cross peaks versus gs-NOESY-HSQC
      cross peaks is caused by diffusion effects and follows the Stejskal-Tanner
      equation. In contrast, the X-half-filtered gs-NOESY-HSQC experiment provides NOE
      cross peaks with reasonable signal-to-noise ratios even for long-range
      interactions in the presence of quadrupolar relaxation. This is demonstrated by
      the spectra of lithium dimethylcuprate.

PMID- 14971016
TI  - Effects of polymorphic differences for sulfanilamide, as seen through 13C and 15N
      solid-state NMR, together with shielding calculations.
AB  - We recorded both carbon-13 and nitrogen-15 NMR spectra of the three solid forms
      of sulfanilamide most commonly known. This study led to an interpretation of the
      solid-state effects seen in cross-polarization magic angle spinning spectra.
      Relaxation times for the different forms were measured. These show different
      behaviour for the three forms, arising from mobility variations. To obtain
      information on local environments, static spectra and spinning sideband manifolds
      were recorded and analysed for the 15N resonances, using isotopically enriched
      samples. Shielding asymmetries and anisotropies for the two nitrogen nuclei were
      obtained, showing very different behaviour for the two sites. Shielding
      calculations were carried out for both 13C and 15N nuclei, and the results are
      discussed in relation to the experimental values.

PMID- 14971017
TI  - Improved method for unambiguous amino acid side-chain 1H and 13C resonance
      assignment.
AB  - Side-chain proton and carbon-13 resonance assignments of [13C;15N]-enriched
      proteins usually rely on combinations of several multi-dimensional experiments.
      Here, we describe a four-dimensional pulse sequence, H(C)C-COSY-TOCSY-(CACO)NH,
      which provides the information required to assign completely aliphatic side-chain
      resonance frequencies. As in widely used HCC(CO)NH-TOCSY experiments, problems
      due to spectral crowding are alleviated by exploiting the dispersion of backbone
      amide 1H and 15N signals. The modification introduced here allows signals from
      different side-chains to be distinguished even in the case of overlap in the
      1H(N)-15N plane of the spectra. For illustration, the new method is applied to
      two proteins with molecular masses of 11 and 23 kDa.

PMID- 14971018
TI  - Physicochemical characterization of the dimeric lanthanide complexes
      [en{Ln(DO3A)(H2O)}2] and [pi{Ln(DTTA)(H2O)}2]2-: a variable-temperature 17O NMR
      study.
AB  - The Gd(III) complexes of the two dimeric ligands [en(DO3A)2] {N,N'-bis[1,4,7
      tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-10-yl-methylcarbonyl]-N,N'
      ethylenediamine} and [pi(DTTA)2]8- [bisdiethylenetriaminepentaacetic acid (trans
      1,2-cyclohexanediamine)] were synthesized and characterized. The 17O NMR chemical
      shift of H2O induced by [en{Dy(DO3A)}2] and [pi{Dy(DTTA)}2]2- at pH 6.80 proved
      the presence of 2.1 and 2.2 inner-sphere water molecules, respectively. Water
      proton spin-lattice relaxation rates for [en{Gd(DO3A)(H2O)}2] and
      [pi{Gd(DTTA)(H2O)}2]2- at 37.0 +/- 0.1 degrees C and 20 MHz are 3.60 +/- 0.05 and
      5.25 +/- 0.05 mM(-1) s(-1) per Gd, respectively. The EPR transverse electronic
      relaxation rate and 17O NMR transverse relaxation time for the exchange lifetime
      of the coordinated H2O molecule and the 2H NMR longitudinal relaxation rate of
      the deuterated diamagnetic lanthanum complex for the rotational correlation time
      were thoroughly investigated, and the results were compared with those reported
      previously for other lanthanide(III) complexes. The exchange lifetimes for
      [en{Gd(DO3A)(H2O)}2] (769 +/- 10 ns) and [pi{Gd(DTTA)(H2O)}2]2- (910 +/- 10 ns)
      are significantly higher than those of [Gd(DOTA)(H2O)]- (243 ns) and
      [Gd(DTPA)(H2O)]2- (303 ns) complexes. The rotational correlation times for
      [en{Gd(DO3A)(H2O)}2] (150 +/- 11 ps) and [pi{Gd(DTTA)(H2O)}2]2- (130 +/- 12 ps)
      are slightly greater than those of [Gd(DOTA)(H2O)]- (77 ps) and [Gd(DTPA)(H2O)]2-
      (58 ps) complexes. The marked increase in relaxivity (r1) of [en{Gd(DO3A)(H2O)}2]
      and [pi{Gd(DTTA)(H2O)}2]2- result mainly from their longer rotational correlation
      time and higher molecular weight.

PMID- 14971019
TI  - Conformational study of a guaiacyl beta-O-4 lignin model compound by NMR.
      Examination of intramolecular hydrogen bonding interactions and conformational
      flexibility in solution.
AB  - Intramolecular H-bonding interactions were investigated in solution for the threo
      and erythro diastereomeric forms of a guaiacyl beta-O-4 lignin model compound by
      using the NMR data obtained from hydroxyl protons. Temperature coefficients of
      the chemical shifts (ddelta/dT) and coupling constants (3J(HCOH)) were measured
      in aprotic and protic solutions: DMSO-d6, acetone-d6 and acetone-d6-water. The
      NMR parameters do not support the existence of strong and persistent
      intramolecular H-bonds that could participate in the stabilization of the
      guaiacyl beta-O-4 structure in solution, but instead indicate that intermolecular
      H-bonds to solvent predominate. 1D NOE experiments nevertheless revealed the
      presence of a direct chemical exchange between the hydroxyl protons, suggesting
      the possible existence of weak and transient intramolecular H-bonding
      interactions. The conformational flexibility of the threo structure was also
      investigated in acetone solution from the measurement of long-range 1H, 1H and
      1H, 13C coupling constants and from NOESY experiments. The NMR data are not
      consistent with any single conformation, indicating that different conformers co
      exist in solution. The experimental results support the conformational
      flexibility predicted by molecular dynamics simulations performed in a previous
      study. Finally, both experimental and theoretical approaches indicate that weak
      intramolecular H-bonds can exist transiently in solution, breaking and reforming
      as the beta-O-4 molecule undergoes conformational interconversion, but cannot be
      invoked as possible means of conferring rigidity to the beta-O-4 structure.

PMID- 14971020
TI  - ESR study of MoY and PdMoY reduction.
AB  - This paper deals with the reduction of MoY and PdMoY using ESR in order to study
      the effect of molybdenum on the reducibility of palladium ions. The evolution of
      signals of paramagnetic species of palladium (Pd3+ in 4d7 and Pd+ in 4d9) and
      molybdenum (Mo5+ in 4d1) was followed by EPR spectroscopy. Two paramagnetic
      species of Mo5+ were observed after reduction under hydrogen, the first with g//
      = 1.87 and the second with g// = 1.89. However, the Mo5+ ion on the zeolite
      exhibited various coordination symmetries upon reduction or other treatments,
      depending on the preparation method. The analysis of the g tensors allowed these
      signals to be attributed to molybdenyl ions in penta- (Mo5+(5C)) and
      hexacoordination (Mo5+(6C))symmetries.

PMID- 14971021
TI  - Complete 1H and 13C NMR assignments of two phytosterols from roots of Piper
      nigrum.
AB  - Using modern NMR techniques, including DQF-COSY, NOESY, HETCOR and HMBC, the full
      assignments of all 1H and 13C chemical shifts were made for stigmastane-3,6-dione
      and stigmast-4-ene-3,6-dione, isolated from the roots of Piper nigrum
      (Piperaceae). Their stereochemistry was resolved by a combination of 2D NOESY
      data and analysis of coupling constants. The two compounds were isolated from the
      genus Piper for the first time.

PMID- 14971022
TI  - Complete 1H and 13C NMR spectral assignment of 17-hydroxy epimeric sterols with
      planar A or A and B rings.
AB  - Complete 1H and 13C spectral assignments of 17beta- and 17alpha-hydroxy epimers
      of three biologically active sterols (boldenone, 3-methoxyestradiol and 3
      methoxydihydroequilenin) were achieved making use of one- and two-dimensional NMR
      techniques (1D-HOHAHA, DEPT, COSY, NOESY, TOCSY, HSQC and COLOC).

PMID- 14971023
TI  - Total assignment of 1H and 13C NMR data for the sesquiterpene lactone 15
      deoxygoyazensolide.
AB  - We describe a complete analysis of the 1H and 13C spectra of the anti
      inflamatory, schistossomicidal and trypanosomicidal sesquiterpene lactone 15
      deoxygoyazensolide. This lactone, with a structure similar to other important
      ones, was studied by NMR techniques such as COSY, HMQC, HMBC, Jres and NOE
      experiments. The comparison of the data with some computational results led to an
      unequivocal assignment of all hydrogen and carbon chemical shifts, even
      eliminating some previous ambiguities. We were able to determine all hydrogen
      coupling constants (J) and signal multiplicities and to confirm the
      stereochemistry. A new method for the determination of the relative position of
      the lactonization and the position of the ester group on a medium-sized ring by
      NMR was developed.

PMID- 14971025
TI  - Mini-review: defense strategies and immunity-related genes.
AB  - The immune system is of crucial importance in defense against infection. It has
      to cope with a large number of different pathogens that relentlessly develop new
      ways to avoid recognition or elimination. Yet most infections are cleared. Immune
      system genes must evolve to keep pace with increasingly sophisticated evasion by
      pathogens. In this article we examine features of human defense genes that
      reflect the demands imposed by such intense selection. Key examples are MHC and
      KIR genes, where features such as polygeny and polymorphism facilitate the
      comprehensive logistics needed to counteract infection.

PMID- 14971026
TI  - Commentary: C-type lectins on the macrophage cell surface--recent findings.
AB  - Interest in the C-type lectin family as a fundamental mediator of diverse immune
      interactions has grown exponentially in recent years, especially concerning
      members expressed on NK cells and their roles in anti-viral and anti-tumor
      immunity. For macrophages, however, collating the roles of the broad range of C
      type lectins expressed may be a more complex task. Analysis of the configuration
      of the C-type lectin(-like) domains among any other conserved modules reveals
      subfamilies of highly divergent structures. The identified ligands are likewise
      highly varied; however, most in vivo ligands are unknown and the significance of
      any recognized interactions is not well understood. In this commentary we review
      key features of C-type lectin and lectin-like receptor expression on macrophages
      and discuss recent data that sheds light on their varied functions. We aim to
      highlight the considerable body of novel/uncharacterized members of this receptor
      family and to place in context the initial description of CLECSF8, which is
      reported in this issue of the journal.

PMID- 14971027
TI  - Developmental status of CD4-CD8+ and CD4+CD8- thymocytes with medium expression
      of CD3.
AB  - In normal mice, more than 10% of thymocytes in the CD4+CD8- and CD4-CD8+ single
      positive (SP) subsets express a medium level of CD3 on the cell surface. However,
      the fate of CD3medium cells is unclear. The CD3medium SP subpopulations might
      contain (i) cells in an immature stage of the pathways leading to CD3high cells,
      (ii) cells in developmental pathways that do not lead to CD3high cells, or (iii)
      cells that have been negatively selected. We found that sorted CD3medium CD4+CD8-
      thymocytes from adult mice up-regulated CD3 to high levels in reaggregation
      thymus organ culture. Unlike their CD3high counterparts, CD3medium CD4+CD8-
      thymocytes were unable to undergo chemotaxis towards the chemokines CCL19 and
      CCL21. CD3medium thymocytes of both CD4+CD8- and CD4-CD8+ subsets were also
      considerably more responsive than CD3high SP cells to apoptotic signals induced
      in vitro by ligation of CD95 (Fas/APO-1) or by dexamethasone. In both SP subsets,
      a higher frequency of thymocytes expressing forbidden Vbeta+ T cell receptors
      reactive with endogenous mammary tumor virus superantigens was found in CD3medium
      subpopulations than in CD3high subpopulations. These findings argue that the
      CD3medium SP thymocyte subpopulations contain apoptosis-susceptible precursor
      cells of CD3high SP cells and are subject to negatively selecting pressures.

PMID- 14971028
TI  - Drug-induced autoantibody formation in mice: triggering by primed CD4+CD25- T
      cells, prevention by primed CD4+CD25+ T cells.
AB  - Although the ability of CD4+CD25+ T suppressor (Ts) cells to prevent experimental
      autoimmune diseases has been described, nothing is known concerning their role
      and mechanism of action in xenobiotic-induced autoimmunity. Procainamide,
      mercuric chloride, and gold(I) are three xenobiotics that can induce autoimmune
      reactions in humans and rodents. After the induction of IgG1 antinuclear
      autoantibodies (ANA) in mice treated with either of the above xenobiotics,
      adoptive transfer of their CD4+CD25+ T cells completely prevented ANA formation
      in recipients treated with the same xenobiotic; transfer of CD8+ T cells was
      ineffective. Furthermore, xenobiotic-primed CD4+CD25+ T cells could also
      partially prevent ANA formation in recipients treated with a different
      xenobiotic. CD4+CD25- T cells from xenobiotic-treated donors failed to suppress,
      but induced de novo IgG1 ANA formation in untreated recipients. Our findings
      suggest that during xenobiotic treatment T cell reactivity may spread from
      xenobiotic-induced, nucleoprotein-related neoantigens to peptides of the
      unaltered nucleoproteins.

PMID- 14971029
TI  - Aggregation of MHC class I molecules on a CD8+ alphabeta T cell clone
      specifically inhibits non-antigen-specific lysis of target cells.
AB  - MHC class I molecules are target molecules recognized by TCR or NK receptors
      encoded in the NK gene cluster or leukocyte receptor cluster. We show that
      aggregation of MHC class I molecules by specific monoclonal antibodies on
      cytotoxic T cells, inhibits the anti-CD94 redirected lysis of P815. This
      inhibition is not the consequence of apoptosis or anergy of the cytotoxic T
      lymphocytes. In contrast, aggregation of MHC class I molecules does not inhibit
      either the anti-CD3 redirected cytotoxicity or the CD94-triggered up-regulation
      of CD25 molecules of the same T cell clone. MHC class I ligand molecules
      expressed by antigen presenting cells and/or T lymphocytes could therefore be
      able to modulate nonspecific cytotoxicity upon interaction with MHC class I
      molecules expressed by effector cytotoxic T lymphocytes.

PMID- 14971030
TI  - Surface receptors identify mouse NK1.1+ T cell subsets distinguished by function
      and T cell receptor type.
AB  - Natural killer T (NKT) lymphocytes rapidly produce several cytokines, including
      IL-4 and IFN-gamma, upon activation, and act as regulatory cells at an early
      interphase of innate and adaptive immune responses. They have been implicated as
      important elements in diverse immune responses including the regulation of
      autoimmune disease, the immune response to infections, and the prevention of
      tumor metastasis. The broad spectrum of their activities suggested that
      functionally different subsets of NKT cells may exist. We demonstrate two
      functionally distinct splenic NKT populations identified by the expression of
      CD49b and CD69, respectively. Each NKT subset was represented by the amplified
      transgenic NKT cell population in a distinct transgenic mouse line expressing a
      CD1d-restricted TCR. CD49bhigh CD69- NKT cells, termed NKT1 cells by us, were
      high producers of IFN-gamma after stimulation, but essentially devoid of IL-4
      synthesizing cells. Most NKT1 cells used diverse (non-Valpha14-canonical) TCR.
      The CD69+ CD49(-/low) NKT cell population, which we term NKT2, produced large
      quantities of IL-4 and substantial amounts of IFN-gamma upon activation and were
      dominated by cells using the canonical Valpha14-Jalpha18 T cell receptor.
      Knowledge of the unique roles of the different NKT cell subsets in specific
      situations will be essential for our understanding of NKT cell biology.

PMID- 14971031
TI  - Dendritic cells generated in the presence of GM-CSF plus IL-15 prime potent CD8+
      Tc1 responses in vivo.
AB  - Dendritic cells (DC) comprise a system of professional antigen-presenting cells,
      which induce the stimulation of very rare antigen-specific naive T cells. DC
      progenitors can be stimulated to differentiate into immature DC by various growth
      factors, including GM-CSF and IL-4. Here we show that IL-15, in combination with
      GM-CSF, is a growth factor for murine DC. Murine bone marrow cells, depleted of T
      cells, B cells, I-A+ cells and Gr-1+ granulocytes, and cultured in the presence
      of GM-CSF plus IL-15 (IL-15 DC), yielded DC expressing high levels of CD11c and
      MHC class II molecules, as well as CD11b. These cells expressed significant
      levels of CD40, CD80 and CD86, and could stimulate allogeneic CD4+ T cells
      efficiently. Interestingly, IL-15 DC were far superior to DC generated with GM
      CSF plus IL-4 in stimulating allogeneic CD8+ T cells in vitro. Consistent with
      this, IL-15 DC induced much more potent antigen-specific CD8+ T cell responses
      with high levels of Th1 cytokines in vivo, compared to DC generated with GM-CSF
      plus IL-4, or with GM-CSF plus TGF-beta, or with GM-CSF alone. Together, these
      data suggest that IL-15 promotes the development of DC, which induce potent Th1
      and Tc1 responses in vivo. This suggests potential roles for these IL-15 DC cells
      in the immunotherapy of tumors and infectious diseases.

PMID- 14971032
TI  - Interleukin 10 regulates cell surface and soluble LIR-2 (CD85d) expression on
      dendritic cells resulting in T cell hyporesponsiveness in vitro.
AB  - Dendritic cells (DC) are unique in their ability to stimulate naive T cells to
      proliferate and to differentiate into effector T cells. DC, however, can also
      inhibit T cell activation and play a role in central and peripheral tolerance. IL
      10 has been shown to render DC tolerogenic by unknown mechanisms. Using a
      combined monoclonal antibody/retroviral expression cloning approach, we show here
      that the inhibitory receptor LIR-2 (leukocyte immunoglobulin-like receptor-2,
      CD85d) is specifically up-regulated by IL-10 on maturing human DC. LPS
      stimulated, LIR-2-transfected DC inhibited the proliferation of T cells in
      autologous, as well as allogeneic culture systems in vitro. In addition,
      overexpression of LIR-2 on resting T cells, which lack LIR-2 expression,
      inhibited T cell proliferation induced by TCR activation. A novel soluble form of
      LIR-2 was detected in culture supernatants of maturing DC. IL-10 treatment of DC
      potently inhibited the production of soluble LIR-2. Recombinant soluble LIR-2 was
      able to completely restore the proliferation of T cells activated with LPS-plus
      IL-10-treated DC. Thus, IL-10 renders DC hypostimulatory by up-regulating cell
      surface LIR-2 and by inhibiting soluble LIR-2 in vitro.

PMID- 14971033
TI  - The inhibitory NK cell receptor CD94/NKG2A and the activating receptor CD94/NKG2C
      bind the top of HLA-E through mostly shared but partly distinct sets of HLA-E
      residues.
AB  - The human non-classical MHC class I molecule HLA-E is a ligand for both an
      inhibitory NK cell receptor (CD94/NKG2A) and an activating receptor (CD94/NKG2C).
      To identify HLA-E surface recognized by both receptors, especially to determine
      if both receptors recognize the same epitope, we made a series of individually
      Ala-substituted HLA-E proteins and analyzed their binding to CD94/NKG2A
      orCD94/NKG2C. Eight HLA-E mutations that significantly impaired HLA-E binding to
      CD94/NKG2A are all found in the top of alpha1/alpha2 domain of HLA-E. These
      results suggest that CD94/NKG2A binds a HLA-E surface equivalent to a NKG2D
      binding site on MICA. Of the eight mutations that impaired HLA-E binding to
      CD94/NKG2A, six significantly impaired HLA-E binding to CD94/NKG2C suggesting
      that CD94/NKG2C also binds a similar surface of HLA-E. Unexpectedly, the two HLA
      E mutations (D69A and H155A) selectively abrogated HLA-E binding to CD94/NKG2A,
      not largely affected CD94/NKG2C. These results indicate that a mostly shared, but
      partly distinct set of HLA-E residues is discriminated by the two receptors.

PMID- 14971034
TI  - CD4 T cells guarantee optimal competitive fitness of CD8 memory T cells.
AB  - We studied the contribution of CD4 T cell help to survival and competitive
      fitness of CD8 memory T cells specific for influenza virus nucleoprotein. In
      agreement with recent studies, the optimal generation of functional memory CD8 T
      cells required CD4 help, although long-term maintenance of resting CD8 memory T
      cells did not absolutely depend on the presence of CD4 T cells. Nonetheless, CD4
      T cells were essential during differentiation of CD8 memory T cells to imprint on
      them the capacity to compete effectively with other memory T cells. CD8 memory
      cells generated with help survived better in secondary polyclonal hosts, and co
      transfer into lymphopenic hosts together with "un-helped" CD8 memory cells showed
      improved homeostatic expansion of CD8 memory cells that had been generated with
      CD4 help. Therefore, the requirement for CD4 help in CD8 T cell memory extends to
      homeostatic parameters that ensure the maintenance and competitive fitness of
      memory clones.

PMID- 14971035
TI  - FcgammaRII expression on follicular dendritic cells and immunoreceptor tyrosine
      based inhibition motif signaling in B cells.
AB  - Immune complexes (IC) initiate immunoreceptor tyrosine-based inhibition motif
      (ITIM) signaling and inhibit B cell activation by coligating B cell receptor for
      antigen (BCR) and FcgammaRII. Nevertheless, IC on follicular dendritic cells
      (FDC) stimulate rapid germinal center (GC) B cell proliferation suggesting that
      interactions between IC and FDC render IC capable of B cell activation. To
      understand this, we studied the kinetics of FDC FcgammaRII and complement
      receptors 1 and 2 (CR1&2) expressions during the GC reaction and determined
      whether FDC FcgammaRII could bind Fc in IC and block ITIM signaling. Mice were
      immunized with sheep red blood cells (SRBC), and CR1&2 and FcgammaRII levels in
      FDC reticula were monitored. The role of FDC FcgammaRII was studied using anti
      BCR-stimulated A20 cells. Levels of FDC FcgammaRII in spleens of SRBC-injected
      mice increased within 24 h and were dramatically increased (approximately 50
      fold) on days 3 and 5. In contrast, CR1&2 levels increased less than twofold.
      Addition of normal FDC, but not FDC lacking FcgammaRII, reduced and reversed anti
      BCR-induced SH2 domain-containing inositol phosphatase (SHIP)-1 phosphorylation
      in A20 cells. FDC were able to induce normal recall responses even after
      overnight incubation of the lymphocytes with IC to stimulate ITIM signaling.
      Engagement of Ig Fc with numerous FcgammaRII on FDC appears to minimize IC
      induced ITIM signaling. Thus, rapid up-regulation of FDC FcgammaRII may explain
      why poorly immunogenic IC are rendered highly immunogenic when presented by FDC
      in GC.

PMID- 14971036
TI  - The neuronal protein Kidins220 localizes in a raft compartment at the leading
      edge of motile immature dendritic cells.
AB  - Kidins220, a protein predominantly expressed in neural tissues, is the first
      physiological substrate for protein kinase D (PKD). We show that Kidins220 is
      expressed in monocyte-derived and in peripheral blood immature dendritic cells
      (im DC). Immature DC (im DC) migrate onto extracellular matrices changing
      cyclically from a highly polarized morphology (monopolar (MP) stage) to a
      morphologically symmetrical shape (bipolar (BP) stage). Kidins220 was localized
      on membrane protrusions at the leading edge or on both poles in MP and BP cells,
      respectively. CD43, CD44, ICAM-3 and DC-SIGN, and signaling molecules PKD, Arp2/3
      were found at the leading edge in MP or on both edges in BP cells, showing an
      intriguing parallelism between morphology and localization of molecular
      components on the poles of the motile DC. F-actin co-localized and it was
      necessary for Kidins220 localization on the membrane in MP and BP cells.
      Kidins220 was also found in a raft compartment. Disruption of rafts with methyl
      beta-cyclodextrin induced rounding of the cells, inhibition of motility and lost
      of Kidins220 polarization. Our results describe for the first time the molecular
      components of the poles of motile im DC and indicate that a novel neuronal
      protein may be an important component among these molecules.

PMID- 14971037
TI  - The mitochondrial phase of the glucocorticoid-induced apoptotic response in
      thymocytes comprises sequential activation of adenine nucleotide transporter
      (ANT)-independent and ANT-dependent events.
AB  - In thymocytes, dexamethasone initiates cytochrome c-dependent processing of
      caspase-9 and the activation of caspase-3 to trigger apoptotic damage. Using
      murine thymocytes or a thymocyte cell line WEHI 7.1, we show that this pathway is
      inhibited by dominant-negative caspase-9, the anti-apoptotic protein Bcl-2, or by
      blocking components of the mitochondrial permeability transition pore complex
      (PTPC). We use DIDS (dithiocyanatostilbene-2,2-disulfonic acid), a
      pharmacological modifier of VDAC (voltage-dependent anion channel) function or
      ectopic expression of hexokinase-II, to examine the role of the VDAC--a
      mitochondrial outer membrane protein--in this apoptotic pathway. This approach
      implicated the VDAC in dexamethasone-mediated cytochrome c release, processing of
      caspase-9 and caspase-3, the loss of mitochondrial transmembrane potential
      (Deltapsim), nuclear damage and cell lysis. Inhibiting the adenine nucleotide
      transporter (ANT), a protein on the mitochondrial inner membrane, also blocks
      dexamethasone-induced apoptosis, but the ANT regulates caspase-3 processing and
      nuclear damage but not the mitochondrial efflux of cytochrome c. Collectively,
      the data identify two separable, but connected events in dexamethasone-induced
      mitochondrial damage in thymocytes. The first event is an increase in
      permeability of the mitochondrial outer membrane leading to VDAC-regulated efflux
      of cytochrome c and initial processing of caspase-9 followed by ANT-dependent
      caspase-3 processing and apoptotic damage to cells.

PMID- 14971038
TI  - Intrahepatic B cell clonal expansions and extrahepatic manifestations of chronic
      HCV infection.
AB  - B cell repertoire in three biological compartments (liver, bone marrow and
      peripheral blood) of 30 unselected patients chronically infected with HCV has
      been characterized. Restriction of humoral immune response defined by enrichment
      of B cell clonal expansions occurred in the liver of 15 patients (50%), in the
      bone marrow and peripheral blood of 2 (6.7%) and 8 (26.7%) patients,
      respectively. An in situ hybridization technique was developed for the detection
      of dominant B cell clones in patients with monoclonal expansions. It was shown
      that morphologically distinct B cell expansion contributes to the formation of
      intraportal follicle-like structures. Sequence analyses of CDRH3 gene segments
      revealed a wide range of variations. Clones derived from the same founder were
      demonstrated simultaneously in the three compartments explored. The occurrence of
      B cell clonal expansions profoundly influenced the clinical expression of HCV
      infection, since it was associated with extrahepatic manifestations. In sharp
      contrast, no extrahepatic signs or disease occurred in patients without evidence
      of intrahepatic B cell clonalities. These findings emphasize the profound B cell
      function derangement in at least half of HCV-infected patients. Thus, the
      restriction of V gene usage has a direct impact on the clinical spectrum of HCV
      infection.

PMID- 14971039
TI  - Identification of a novel thioredoxin-related protein, PC-TRP, which is
      preferentially expressed in plasma cells.
AB  - Using cDNA subtraction we have identified a previously unknown cDNA, termed
      plasma cell thioredoxin-related protein (PC-TRP), which was overexpressed in
      plasma cells in vitro. The full-length 2636-bp PC-TRP cDNA contained an open
      reading frame coding for 417 amino acids. The cDNA sequence was mapped to a
      region on mouse chromosome 13 and the PC-TRP gene consists of ten exons
      distributed over a 28-kb region. The PC-TRP was found to contain three atypical
      thioredoxin domains and showed functional thioredoxin activity in vitro. A more
      detailed analysis revealed that PC-TRP was expressed at a high level in plasma
      cells, both at the mRNA and protein level, while present at very low levels in
      all other cells and tissues examined. Immunohistological analysis revealed that
      PC-TRP was expressed at high levels in all plasma cells isolated from bone marrow
      or lamina propria, irrespective of their Ig isotype. In the spleen, however, 60%
      of the IgG-expressing plasma cells showed only a dull staining at day 14 after
      immunization, while >90% of the IgG-secreting cells in the spleen expressed PC
      TRP at day 21 after immunization. In addition, an IgG-secreting, PC-TRPdull
      plasma cell population could also be observed after B cell activation in vitro.

PMID- 14971040
TI  - An interaction between CD16 and CR3 enhances iC3b binding to CR3 but is lost
      during differentiation of monocytes into dendritic cells.
AB  - The receptor for the iC3b fragment of complement, CR3, is involved in
      monocytes/macrophages and neutrophils phagocytosis. CR3 is known to interact with
      the low affinity receptor for Ig (CD16) and previous studies have suggested that
      this cooperation modulates CR3 functions. Herein we have studied the effect of
      CD16 on the ability of human monocytes CR3 to bind to iC3b. We show that iC3b
      binding to CR3 is inhibited by several reagents that are known to dissociate the
      CD16/CR3 complex. In addition, treatment of monocytes with soluble CD16 inhibited
      iC3b binding to CR3. Together, these data indicate that iC3b binding to monocyte
      CR3 is up-regulated by an interaction between membrane CD16 and CR3. The
      implication of CD16 in CR3 binding to iC3b was also analyzed after monocyte
      differentiation into dendritic cells (DC). Differentiation of monocytes into DC
      abrogates the cooperation between CD16 and CR3, due to a loss of CD16/CR3
      interaction. In accordance, this phenomenon is associated with a lack of iC3b
      binding to DC. As a consequence, deposition of iC3b on apoptotic cells does not
      modify their phagocytosis by DC. In conclusion, we demonstrate a cooperation
      between CD16 and CR3 that favors iC3b binding to CR3 but is lost on DC.

PMID- 14971041
TI  - Morphological changes during dendritic cell maturation correlate with cofilin
      activation and translocation to the cell membrane.
AB  - Upon activation, tissue residing immature dendritic cells (DC) start to migrate
      towards the draining lymph node and mature into efficient antigen-presenting
      cells. During maturation DC loose their capacity to endocytose antigens, change
      their surface expression of adhesion molecules, chemokine receptors, and
      costimulatory molecules, and change morphology. We employed 2D-PAGE and mass
      spectrometry to identify additional differentially expressed proteins in immature
      and mature DC. Human monocyte-derived DC were matured with LPS and protein
      expression profiles were compared before and after maturation. One of the
      proteins differentially expressed between immature and mature DC was identified
      as the actin-binding protein cofilin. We show here that cofilin is
      dephosphorylated in response to several maturation stimuli (i.e. CD40 ligand, LPS
      or a combination of TNF-alpha and prostaglandin E2). Moreover, dephosphorylated
      cofilin translocated towards the plasma membrane during maturation. Importantly,
      this correlated with an increase in filamentous actin and the appearance of
      veils, suggesting a role for cofilin in cytoskeletal rearrangements during
      maturation.

PMID- 14971042
TI  - Characterization of MHC- and TCR-binding residues of the myelin oligodendrocyte
      glycoprotein 38-51 peptide.
AB  - Myelin oligodendrocyte glycoprotein (MOG) is a major experimental autoimmune
      encephalomyelitis (EAE) antigen in H-2b mice and a potential autoantigen in
      multiple sclerosis. How well MOG peptides bind to MHC and how TCR recognize the
      peptide/MHC complex have important implications for thymic selection as well as T
      cell activation in the periphery. In this study, we have characterized amino
      acids in the MOG(38-51) peptide important for peptide binding to I-Ab, and for
      TCR recognition of the peptide/MHC complex. We found that the amino acids R41,
      F44, R46 and V47 constituted the major TCR contact residues, as alanine
      substitution at these positions abrogated T cell responses without decreasing
      their binding affinity to I-Ab. In addition, G38 and W39 were found to be minor
      TCR contact residues. Finally, substituting tyrosine for alanine at position 40
      decreased binding to I-Ab by approximately 50% and prevented induction of T cell
      responses in C57BL/6J mice upon immunization. Thus, Y40 is the dominant MHC
      binding residue of the MOG(38-51) peptide and most likely occupies the p1 pocket
      of I-Ab. Our results could be useful to design peptides with altered agretopes
      and epitopes of the MOG(38-51) peptide to study their therapeutic potential in
      the EAE model.

PMID- 14971043
TI  - Pulmonary tuberculosis in BALB/c mice with non-functional IL-4 genes: changes in
      the inflammatory effects of TNF-alpha and in the regulation of fibrosis.
AB  - In BALB/c mice, as in man, progressive pulmonary tuberculosis is accompanied by
      increasing expression of IL-4. Therefore we have used BALB/c mice with disrupted
      IL-4 genes (IL-4(-/-)) to investigate the role of IL-4 in pulmonary tuberculosis,
      with particular emphasis on the toxicity of TNF-alpha and on fibrosis, both of
      which are neglected aspects of human tuberculosis. Delayed-type hypersensitivity
      (DTH) sites in IL-4(+/+) mice were sensitive to the toxicity of locally injected
      TNF-alpha, whereas DTH sites in IL-4(-/-) mice were not. However, intravenous
      administration of IL-4 to IL-4(-/-) mice restored the sensitivity of the DTH
      sites to pro-inflammatory effects of TNF-alpha. In late disease, the lungs of IL
      4(+/+) mice expressed low IFN-gamma, but high TGF-beta and IL-4, correlating with
      fibrosis, detected as a high hydroxyproline content. In contrast, TGF-beta peaked
      7 days after infection in the lungs of the IL-4(-/-) mice, and then fell to very
      low levels in the late disease, while IFN-gamma remained high. Accordingly,
      hydroxyproline content was reduced in infected IL-4(-/-) mice compared to IL
      4(+/+) controls. In conclusion, the findings suggest that IL-4 has modestly
      detrimental effects on the antibacterial efficacy of the Th1 response, and larger
      effects on the toxicity of TNF-alpha, and on fibrosis.

PMID- 14971044
TI  - Antibody-mediated bacterial clearance from the lower respiratory tract of mice
      requires complement component C3.
AB  - To assess the contribution of complement to respiratory immunity in the context
      of a natural bacterial infection, we used mice genetically deficient in
      complement components and the murine pathogen Bordetella bronchiseptica.
      Complement component C3 was not required for the control of bacterial infection
      or for the generation of infection-induced protective immunity. However, C3
      deficient (C3(-/-)) mice were severely defective, compared to wild type, in
      vaccine-induced protective immunity. Adoptively transferred immune serum from
      convalescent wild-type or C3(-/-) animals rapidly cleared B. bronchiseptica from
      the lungs of wild-type mice but did not affect its growth in C3(-/-) mice,
      indicating that the defect is not in the generation of protective immunity, but
      in its function. Immune serum was effective in C5-deficient mice but had little
      effect in the lungs of mice lacking either Fcgamma receptors (FcgammaR) or CR3,
      suggesting bacterial clearance is not via direct complement-mediated lysis.
      Together, these data indicate that complement is required for antibody-mediated
      clearance of Bordetella and suggest the mechanism involves C3 opsonization of
      bacteria for phagocytosis that is both CR3- and FcgammaR-dependent.

PMID- 14971045
TI  - Cross-priming of CD8+ T cells by viral and tumor antigens is a robust phenomenon.
AB  - "Cross-priming" refers to the activation of naive CD8+ T cells by antigen
      presenting cells that have acquired nominal antigens from another cell. The
      biological relevance of cross-priming of CD8+ T cells has recently been
      challenged (Zinkernagel, R. M., Eur. J. Immunol. 2002. 32: 2385-2392), on the
      basis that responses are weak or poorly quantitated, and the determinants
      recognized are undefined. Here we show that cross-priming is a robust process
      that elicits vigorous primary responses to multiple peptides in two well-defined
      systems. Our findings support the relevance of cross-priming in CD8+ T cell
      responses to viruses and tumor cells, and demonstrate that cross-priming elicits
      CD8+ T cells to determinants generated by the endogenous processing pathway.

PMID- 14971046
TI  - Arginase induction promotes Trypanosoma cruzi intracellular replication in
      Cruzipain-treated J774 cells through the activation of multiple signaling
      pathways.
AB  - Given that arginase activation may effectively influence nitric oxide (NO)
      production in macrophages, we have investigated the intracellular signals that
      regulate L-arginine metabolism and its influence on Trypanosoma cruzi growth. We
      demonstrate that cruzipain (Cz), a parasite antigen, induces arginase I
      expression in J774 cells, and the pretreatment of Cz-treated cells with N-omega
      hydroxy-L-arginine (arginase inhibitor) leads to a dramatic decrease in
      amastigote growth. The study of intracellular signals shows that genistein
      [tyrosine kinase (TK) inhibitor], KT5720 [protein kinase (PK) A inhibitor] and
      SB203580 [p38 mitogen-activated protein kinase (MAPK) inhibitor] significantly
      decrease Cz-induced arginase activation. However, calphostin C (PKC inhibitor)
      and PD98059 [p44/p42 MAPK kinase (MEK) inhibitor] did not cause a significant
      change. To determine if signaling pathways triggered by Cz were involved in the
      T. cruzi growth, we studied the effect of those inhibitors. In Cz-treated cells-
      pre-incubated with TK, PKA or p38 MAPK inhibitors--the balance of NO/urea was
      biased towards NO, and the amastigote growth was diminished. Besides, genistein
      and mainly KT5720 induced down-regulation of arginase I expression in Cz-treated
      cells. Thus, activation of TK, PKA and p38 MAPK by Cz induces an increase of
      arginase activity in macrophages and the subsequent T. cruzi growth.

PMID- 14971047
TI  - The human C-type lectin CLECSF8 is a novel monocyte/macrophage endocytic
      receptor.
AB  - Cell surface lectin receptors play important roles in the function of
      macrophages. Herein, we have identified and characterized the human orthologue of
      the mouse Mcl/Clecsf8. Human CLECSF8 codes for a type II membrane glycoprotein of
      215 amino acids that belongs to the human calcium-dependent lectin family (C-type
      lectin). The cytoplasmic tail of CLECSF8 lacks consensus signaling motifs and its
      extracellular region shows a single carbohydrate recognition domain (CRD). The
      CLECSF8 gene has been localized on the telomeric region of the NK gene complex on
      chromosome 12p13 close to MINCLE. CLECSF8 mRNA shows a monocyte/macrophage
      expression pattern. Biochemical analysis of CLECSF8 on transiently transfected
      cells showed a glycoprotein of 30 kDa. Cross-linking of the receptor leads to a
      rapid internalization suggesting that CLECSF8 constitutes and endocytic receptor.

PMID- 14971048
TI  - Complement C1q regulates LPS-induced cytokine production in bone marrow-derived
      dendritic cells.
AB  - We show here that C1q suppresses IL-12p40 production in LPS-stimulated murine
      bone marrow-derived dendritic cells (BMDC). Serum IL-12p40 concentration of C1q
      deficient mice was higher than that of wild-type mice after intraperitoneal LPS
      injection. Because neither globular head of C1q (gC1q) nor collagen-like region
      of C1q (cC1q) failed to suppress LPS-induced IL-12p40 production, both gC1q and
      cC1q, and/or some specialized conformation of native C1q may be required for the
      inhibition. While C1q did not affect mRNA expression of Toll-like receptor 4
      (TLR4), MD-2, and myeloid differentiation factor 88 (MyD88), BMDC treated with
      C1q showed the reduced activity of NF-kappaB and the delayed phosphorylation of
      p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase after LPS
      stimulation. CpG oligodeoxynucleotide-induced IL-12p40 and TNF-alpha production,
      another MyD88-dependent TLR-mediated signal, was also suppressed by C1q
      treatment. Therefore, C1q is likely to suppress MyD88-dependent pathway in TLR
      mediated signals. In contrast, C1q failed to suppress colony formation of B cells
      responding to LPS or LPS-induced CD40 and CD86 expression on BMDC in MyD88
      deficient mice, indicating that inhibitory effects of C1q on MyD88-independent
      pathways may be limited. Taken together, C1q may regulate innate and adaptive
      immune systems via modification of signals mediated by interactions between
      invading pathogens and TLR.

PMID- 14971049
TI  - Dominance of CCL22 over CCL17 in induction of chemokine receptor CCR4
      desensitization and internalization on human Th2 cells.
AB  - Chemokines and their receptors play a pivotal role in controlling T cell
      trafficking in immunity and inflammation. Two chemokines, CCL17 and CCL22,
      activate the chemokine receptor CCR4, expressed on functionally distinct subsets
      of T cells: cutaneous leukocyte-associated antigen (CLA)+ skin-homing, T helper
      (Th) 2, and CD25+ T suppressor cells. Here, we compared the ability of CCL17 and
      CCL22 to promote CCR4 internalization as a mechanism of regulation of receptor
      function on human Th2 cells. We report that CCL22 is a potent and rapid inducer
      of CCR4 internalization, while CCL17 is not. CCR4 internalization does not
      require G protein coupling, while being dependent on lipid rafts integrity and
      clathrin-coated pits functionality. Cell surface disappearance of CCR4 is rapidly
      reversed upon removal of exogenous ligand by virtue of receptor recycling. CCR4
      internalization leads to a loss of functional responsiveness, while recovery of
      surface expression leads to re-acquisition of chemotactic sensitivity of Th2
      cells. The differential CCR4 desensitization and internalization reported here
      and the distinct expression patterns of CCL17 and CCL22 observed in vivo suggest
      that while CCL17 may act first on CCR4 at the endothelial surface to promote
      vascular recognition, CCL22 could subsequently engage the receptor within the
      tissue microenvironment to guide cellular localization.

PMID- 14971050
TI  - Cyclopentenone prostaglandins induce endothelial cell apoptosis independent of
      the peroxisome proliferator-activated receptor-gamma.
AB  - Cyclopentenone prostaglandins (CP-PG), such as prostaglandin A1 (PGA1) or 15
      deoxy-Delta(12,14)-prostaglandin J2 (PGJ2), induce apoptosis in different cell
      types. PGJ2 is also a potent activator of the peroxisome proliferator-activated
      receptor-gamma (PPARgamma). We investigated whether PPARgamma regulates CP-PG
      induced apoptosis in endothelial cells (EC). We show that CP-PG induce apoptosis
      in human umbilical vein EC (HUVEC). Incubation with PGA1 or PGJ2 for 24 h reduced
      HUVEC number and viability, while the synthetic activators Wy14643 or
      rosiglitazone had no effect. Flow cytometry and cell cycle analysis revealed
      externalized phosphatidylserine, caspase-3 activation, and an increased
      percentage of cells with a reduced DNA content by CP-PG treatment. EMSA
      demonstrated an activation of PPARgamma by PGJ2 and rosiglitazone.
      Immunohistochemistry of HUVEC and immunoblot analyses of protein extracts showed
      that PPARgamma was localized in the nuclei of HUVEC, and that CP-PG treatment
      decreased the amount of PPARgamma protein. This degradation was prevented by a
      pan-caspase inhibitor. Treatment of differentiated, endothelial-like PPARgamma
      deficient stem cells, or of HUVEC transfected with dominant-negative PPARgamma
      with CP-PG, induced cell death and apoptosis. Our findings show that PGA1 and
      PGJ2 induce apoptosis in endothelial cells independent of PPARgamma. As the
      synthesis of PGJ2 is increased at sites of inflammation, our results may suggest
      a possible mechanism for endothelial damage.

PMID- 14971051
TI  - Characterization of three CpG oligodeoxynucleotide classes with distinct
      immunostimulatory activities.
AB  - Oligodeoxynucleotides (ODN) with unmethylated deoxycytidyl-deoxyguanosine (CpG)
      dinucleotides (CpG ODN) mimic the immunostimulatory activity of bacterial DNA and
      are recognized by the Toll-like receptor 9 (TLR9). CpG ODN of the B-Class
      stimulate strong B cell and NK cell activation and cytokine production. The
      highest degrees of NK stimulation as well as IFN-alpha secretion by plasmacytoid
      DC were found to occur only with A-Class ODN. A third class of CpG ODN combines
      the immune effects of A- and B-Class CpG ODN. C-Class ODN strongly stimulate B
      cell or NK cell activation and IFN-alpha production. In contrast to the A-Class,
      the C-Class is wholly phosphorothioate, has no poly-G stretches, but has
      palindromic sequences combined with stimulatory CpG motifs. All classes stimulate
      TLR9-dependent signaling, but with strikingly different dose-response
      relationships that are quite in contrast to those observed for IFN-alpha. Effects
      similar to those on human cells were observed on mouse splenocytes. In contrast,
      splenocytes from TLR9-deficient mice did not show any response to the three CpG
      ODN classes. In vivo studies demonstrate that C-Class ODN are very potent Th1
      adjuvants. C-Class ODN may represent new therapeutic drugs that combine the
      effects of A- and B-Class ODN for broad applications in infectious disease or
      cancer therapy.

PMID- 14971052
TI  - Autoantibodies in autoimmune thyroid disease promote immune complex formation
      with self antigens and increase B cell and CD4+ T cell proliferation in response
      to self antigens.
AB  - B cells are centrally involved as antigen-presenting cells in certain autoimmune
      diseases. To establish whether autoantibodies form immune complexes (IC) with
      self-antigens in autoimmune thyroid disease (AITD) and promote B cell uptake of
      self-antigen, sera from patients with Hashimoto's thyroiditis (HT), Graves'
      disease (GD) and healthy controls were incubated with human thyroglobulin (Tg)
      before adding normal peripheral blood mononuclear cells. The deposition of
      immunoglobulins and C3 fragments on B cells was then assessed. Inclusion of Tg in
      serum from HT patients promoted B cell capture of IgG and C3 fragments.
      Furthermore, the binding of Tg to B cells in preparations of normal blood cells
      was higher in HT serum than in serum from controls and correlated positively with
      the serum anti-Tg activity, as did the B and CD4+ T cell proliferation.
      Disruption of the three-dimensional structure of Tg by boiling reduced the
      proliferative responses. The data indicate that anti-Tg antibodies associated
      with AITD facilitate the formation of complement-activating Tg/anti-Tg complexes,
      binding of IC to B cells, and the subsequent proliferation of B and T cell
      subsets. This represents a novel mechanism for the maintenance of autoimmune
      processes in AITD and links autoreactive T cell responses with the presence of
      autoantibodies.

PMID- 14971053
TI  - DNase I behaves as a transcription factor which modulates Fas expression in human
      cells.
AB  - DNase I is the major nuclease present in biological fluids and is ubiquitously
      expressed in mammalian tissues. It is responsible for the removal of DNA from
      nuclear antigens, and consistently with this function, DNase I-deficient mice
      show features of autoimmunity. The enzyme seems also to be involved in apoptosis
      (programmed cell death). We demonstrate that DNase I is internalized by human
      cells upon binding mannose 6-phosphate receptor and gains access into the cells.
      Following internalization of the enzyme, the cells show an increased surface
      expression of Fas molecule, a key regulator of apoptosis. Here we show that DNase
      I up-regulates fas transcription upon interaction with the fas gene promoter.
      Moreover, overexpression of the DNase I gene in human cells results in a similar
      modulation of the fas gene expression. Our data provide the first evidence that
      the endonuclease DNase I behaves as a transcription factor which selectively
      regulates cell surface Fas expression in human cells and point towards a
      fundamental role of DNase I in the regulation of the apoptotic machinery.

PMID- 14971054
TI  - Identification of T cell epitopes on human proteolipid protein and induction of
      experimental autoimmune encephalomyelitis in HLA class II-transgenic mice.
AB  - Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the CNS
      that is associated with HLA class II molecules HLA-DR2, -DR3 and -DR4.
      Previously, it has been difficult to analyze the role of individual HLA molecules
      in disease pathogenesis due to heterogeneity of MHC genes, linkage
      disequilibrium, influence of non-MHC genes and contribution of environment. To
      overcome some of these problems, we have generated HLA-transgenic (tg) mice to
      investigate function and interaction of these molecules in disease pathogenesis.
      To investigate the role of individual HLA class II genes in immune responses to
      human proteolipid protein (PLP), a candidate autoantigen in MS, mice expressing
      HLA genes DR2, DR3, DR4 (DRB1*0401 and DRB1*0402), DQ6 and DQ8, lacking
      endogenous class II molecules were immunized with overlapping peptides of PLP. In
      all tg mice, the majority of the dominant T cell epitopes were clustered mainly
      to three region; amino acids 31-70, 91-120 and 178-228, of the PLP molecules. We
      also identified an encephalitogenic epitope PLP(91-110) that induced clinical EAE
      in HLA-DR3 tg mice. These tg mice had inflammatory infiltrates classically
      associated with EAE and showed a Th1 cytokine profile. This humanized mouse model
      of MS will be valuable in deciphering the role of HLA molecules and autoantigens
      in MS.

PMID- 14971055
TI  - Knocking out IL-6 by vaccination.
AB  - Inappropriate expression of IL-6 plays a role in various inflammatory conditions,
      degenerative diseases, and cancers. Several model systems have been developed
      that can specifically block IL-6-receptor interactions. Here we present a simple
      and highly effective approach based on vaccination with a pool of specifically
      mutated IL-6 analogues to induce a neutralizing IL-6 antibody response in mice.
      Judged by the ability of the analogues to bind to heterologous anti-IL-6
      antibodies and cellular IL-6 receptors the IL-6 analogues seemed to have a three
      dimensional structure comparable to that of wild-type IL-6. Injection of them
      broke self-tolerance and induced an immune response to IL-6, presumably because
      of the amino acid differences between the analogues and wild-type IL-6. This
      resulted in a long-lasting anti-IL-6 antibody-mediated IL-6 deficiency that
      blocked experimentally induced IL-6-mediated pathology.

PMID- 14971056
TI  - How much at risk are cone snails?

PMID- 14971057
TI  - Letrozole in breast cancer.

PMID- 14971058
TI  - Letrozole in breast cancer.

PMID- 14971059
TI  - Letrozole in breast cancer.

PMID- 14971060
TI  - Letrozole in breast cancer.

PMID- 14971061
TI  - Implantable cardioverter-defibrillators and complications.

PMID- 14971062
TI  - Paroxetine and the FDA.

PMID- 14971064
TI  - Avoid construction nightmares by taking charge of the process and setting rules.
AB  - A construction crew in your ED guarantees some level of disruption, but you can
      keep your department functioning well by hiring contractors familiar with health
      care settings and establishing ground rules up front. The ED manager must be firm
      about patient safety and unnecessary disruptions. You can reasonably expect
      contractors and their crews to behave appropriately in your ED. Don't stop
      construction work unless necessary, or you may incur costly penalties.

PMID- 14971065
TI  - Increase capacity with chest pain accreditation.

PMID- 14971066
TI  - Headache, abdominal pain pose liability risk.

PMID- 14971067
TI  - A billing analyst can find $300,000 for your ED.

PMID- 14971068
TI  - ED accreditation update. Disease-specific certification links EDs to continuum of
      care, may reduce return visits by the chronically ill.

PMID- 14971069
TI  - The state of CPOE in healthcare: an explanation for our critics.

PMID- 14971070
TI  - The value of CPOE in ambulatory settings.

PMID- 14971071
TI  - Why CPOE must become SOP.

PMID- 14971072
TI  - CPOE: show me the benefits!

PMID- 14971073
TI  - Perks and pains: the trials of IT implementation initiatives.

PMID- 14971074
TI  - Leading patient safety expert speaks on CPOE implementation strategy and success
      factors. Interview by Richard D. Lang.

PMID- 14971075
TI  - Alamance Regional Medical Center improves patient safety with CPOE.
AB  - While it is widely written that advanced clinical information systems can help
      healthcare organizations reduce adverse medical events and increase patient
      safety, Alamance Regional Medical Center (ARMC) has proven that it truly does.
      ARMC chose Eclipsys' Sunrise Clinical Manager for its ability to provide
      knowledge-based clinical decision support and its alert capabilities at the time
      of order entry. Since its organization-wide rollout in summer 2000, ARMC has been
      using the computerized physician order entry (CPOE) system with widespread
      success and has transformed the care delivery process.

PMID- 14971076
TI  - Thinking beyond CPOE to integrated IT strategy and management.
AB  - There is a tremendous amount of pressure driving organizations to implement
      computerized provider order entry. To unlock the greatest value, a more
      enterprise-wide strategic approach to healthcare IT is needed.

PMID- 14971077
TI  - Assessing recommendations from the IOM's quality chasm report.
AB  - The most recent Institute of Medicine report recommends immense changes for
      healthcare institutions and places information technology as a central component
      of proposed changes. This paper gives an overview of the IOM report, analyzes
      several key IT topics, and suggests required actions to effect the IOM's
      recommendations.

PMID- 14971078
TI  - CPOE systems: success factors and implementation issues.
AB  - The medication error dilemma has come to the forefront of most hospitals'
      improvement agendas. The most often cited solution to the problem has been
      computerized provider order entry (CPOE) systems. These systems have significant
      potential to improve errors associated with illegibility as well as inappropriate
      drug use and dosing. On the other hand, CPOE system implementation is fraught
      with barriers that impede acceptance and use of these systems. Knowing what
      strategies have proven successful and what upfront analysis is required can help
      increase the chances of success and ultimately improve the quality of patient
      care.

PMID- 14971079
TI  - The economic effect of implementing an EMR in an outpatient clinical setting.
AB  - Central Utah Multi-Specialty Clinic, a 59-physician group with practices in nine
      locations treating 200,000 active patients, documented the economic impact of
      implementing an electronic medical record. During the one-year period of the
      study, the clinic experienced direct reductions in spending and increases in
      revenue of more than $952,000 compared with the prior year, and anticipates
      cumulative savings of more than $8.2 million over the next five years.

PMID- 14971080
TI  - National health data warehouse: issues to consider.
AB  - A national data warehouse that links public and private data could be used to
      monitor trends in healthcare costs, utilization, quality of care, and adherence
      to quality guidelines and changes in treatment protocols. The development of the
      data warehouse, however, would require overcoming a number of political and
      technical challenges to gain access to private insurance data. This article
      outlines recommendations from a national conference sponsored by the Agency for
      Healthcare Research and Quality (AHRQ) on the private sector's role in quality
      monitoring and provides an operational outline for the development of a national
      private sector health data warehouse.

PMID- 14971081
TI  - Case study: a health check-up for the corporate IT department.
AB  - As advances such as the electronic charting, closed-loop medication safety,
      physician order entry, consumer portals, electronic collaboration, and wireless
      access become the norm, central IS organizations are finding it difficult to keep
      pace. This challenge is exacerbated by declining margins, severe cost pressures,
      increased regulation, and added public scrutiny. Is your centralized IS
      organization healthy enough to meet the challenges presented by today's complex,
      demanding, dynamic healthcare delivery environments? How do you know? What
      factors do you consider?

PMID- 14971082
TI  - Using BPI and emerging technology to improve patient safety.
AB  - Capitalizing on existing IT investments, INTEGRIS Health, a 15-hospital system in
      Oklahoma, is applying business process integration (BPI) methodology and
      technology to leverage legacy systems and staff resources. The resulting project
      uses manual (human) and system tasks to compare real-time information across
      systems to eliminate preventable adverse drug events caused by medication
      ordering errors. Clinicians can quickly see where potential safety risks are
      occurring and change medication orders to prevent harm to the patient.

PMID- 14971083
TI  - Physician use of IT: results from the Deloitte Research Survey.
AB  - The authors analyzed 1,200 physician responses to a Deloitte Research/Fulcrum
      Analytics survey of office-based physician use of the Internet and other
      information technology (IT). Overall, the results suggest that 40 to 50 percent
      of all respondents are using, or are ready to use, IT for substantial clinical
      care. However, time and liability concerns about patient e-mail were pervasive
      across all IT user categories. The results also indicate that some public/private
      policies aimed at increasing physician IT use for clinical management should be
      tailored to specific segments of the physician IT user spectrum, rather than
      using a "one-size-fits-all" policy approach.

PMID- 14971084
TI  - Factors affecting patient-physician communication via the Internet.
AB  - Patients with chronic diseases would potentially benefit greatly from more rapid
      communication with their health provider of their medical status, healthcare
      concerns, and personal medical information such as vital signs, blood sugar, and
      medication use. This study surveyed patients in a multidisciplinary transplant
      and liver disease clinic to determine whether they would consider using an
      Internet-based system for medical management of their illness, what specific
      factors would impact their use of such a system, and what limitations might be
      encountered with respect to patient education, socioeconomic status, and Internet
      access.

PMID- 14971085
TI  - Mortality in rheumatoid arthritis patients treated with or without methotrexate.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease associated with excess
      mortality. In 1974 a registry of RA patients was established at the Wichita
      Arthritis Center. It has been directed by its founder, Dr. Frederick Wolfe, ever
      since. The database for RA patients provided results for the present study and 1
      of the 4 series reported previously. RESULTS: These are based on a consecutive
      series (after specific exclusions) of RA patients, 18 years of age and older,
      treated at the Wichita Arthritis Center, 1981 through 1999. During this period,
      588 of the total 1240 RA patients were treated with methotrexate, and 652
      patients did not receive any methotrexate. Total exposure amounted to 7584
      patient-years, and total deaths numbered 191. An elaborate statistical method was
      developed by Wolfe and a team of Harvard epidemiologists to adjust for prognostic
      risk factors, which were higher in the methotrexate than in the non-methotrexate
      group. Detailed descriptive data were included in the database. Overall excess
      mortality in comparison with population rates was higher in the methotrexate than
      in the non-methotrexate group, but the unadjusted difference was not significant.
      Results for the 1981-1999 total Wichita cohort were compared with those of the
      1974-1990 cohort and the 1983 Impairment Study (both before and after adjustment
      to the older age distribution of the Wichita patients). CONCLUSION: Mortality
      improved somewhat in the RA patients at the Wichita Center from 1974-1990 to 1980
      1999. In the later period, mortality was lower in patients treated with
      methotrexate than in those not so treated. After the authors of the source
      article made adjustments for the increased RA severity in the patients treated
      with methotrexate, mortality was significantly lower in the methotrexate-treated
      group, with a mortality hazard ratio of 0.4 (95% confidence interval 0.2-0.8).

PMID- 14971086
TI  - Outcome of early surgery compared to surveillance in the management of small
      aortic aneurysms--a comparative mortality analysis.
AB  - When underwriting individuals with aortic aneurysms, the following factors are
      used in risk selection: location, initial size, stability or velocity of change
      in size and co-morbid impairments. Treatment options based on clinical and
      ultrasonic findings are either surveillance or surgical resection. A recent study
      examined the 8-year outcome of early-surgery vs surveillance in small (4.6 cm)
      aortic aneurysms. Over the duration, the early-surgery group had a mortality
      ratio of 170% and excess death rate of 28; the surveillance group had a mortality
      ratio of 215% and excess death rate of 45. First-year mortality was expectedly
      high in the early-surgery group. Excluding first-year experience, the early
      surgery group had an improved mortality ratio of 160% and excess death rate of
      22. After 6 months, the death rate in the early-surgery group was about three
      fourths that of the surveillance group. However, due to high initial mortality
      cumulative survival curves did not cross in favor of early-surgery until about 3
      years.

PMID- 14971087
TI  - Excess mortality in remote symptomatic epilepsy.
AB  - BACKGROUND: Published estimates of excess mortality associated with epilepsy vary
      greatly. How much, if any, of the excess is attributable to the seizures
      themselves as opposed to an underlying condition causing the epilepsy is not
      clear from the literature. This article offers evidence that epilepsy per se is
      associated with excess mortality. The excess varies according to severity and
      frequency of seizures. MATERIALS AND METHODS: The authors studied mortality rates
      of developmentally disabled persons in California with and without epilepsy. In
      order to focus on the effect on mortality risk of epilepsy per se, they included
      only persons with good motor function (able to walk and climb stairs) and at
      worst moderate mental retardation (MR). The data were 506,204 person-years and
      1523 deaths among 80,682 California subjects of age 5 to 65 years during the 1988
      1999 study period. Mortality rates for persons with epilepsy were compared to
      rates for persons with no history of epilepsy. RESULTS: Mortality rates were
      higher for persons with epilepsy than for those without. Excess death rates
      (EDRs) varied according to type and frequency of seizures. Combined EDRs were 6
      (deaths per 1000 person-years) for persons with recent (< 12 months) history of
      status epilepticus, 5 for recent history of generalized tonic-clonic (GTC)
      seizures, 3 for recent history of seizures but no recent GTC seizures, and less
      than 1 for a history of seizures but no recent events. CONCLUSIONS: The data
      presented here are evidence that epilepsy per se is associated with increased
      mortality. The EDRs reported here may be better measures of excess mortality due
      to epilepsy than previously published estimates.

PMID- 14971088
TI  - Recurrent PSA after prostatectomy for prostate cancer: implications of PSA
      doubling time.
AB  - After radical prostatectomy for prostate cancer, men frequently develop
      detectable levels of prostate specific antigen (PSA). A slow rate of increase, as
      characterized by the PSA doubling time (PSADT) is the principal marker for a
      favorable prognosis. Data and results presented in 2 recent clinical articles
      studying cohorts of men with clinical stage T1/T2 prostate cancer are reviewed
      and used to develop mortality analyses. Life-table analysis shows a mortality
      ratio of 257% at 5 years for Gleason score < 8, PSA recurrence > 2 years after
      surgery for clinical stage T1/T2 disease, and PSA doubling time (PSADT) > 10
      months. Markov modeling using transition probabilities derived from the clinical
      articles to develop a life table analysis yields a mortality ratio of 145% at 10
      years for similar patients.

PMID- 14971089
TI  - Insurance and epidemics: SARS, West Nile virus and Nipah virus.
AB  - Severe acute respiratory syndrome (SARS) reminds us that sudden disease emergence
      is a permanent part of our world--and should be anticipated in our planning.
      Historically the emergence of new diseases has had little or no impact beyond a
      small, localized cluster of infections. However, given just the right conditions,
      a highly virulent pathogen can suddenly spread across time and space with massive
      consequences, as has occurred on several occasions in human history. In the wake
      of the SARS outbreak, we are now forced to confront the unpleasant fact that
      human activities are increasing the frequency and severity of these kinds of
      emergences. The idea of more frequent biological "invasions" with economic and
      societal impacts comparable to SARS, presents stakeholders in and the global
      economy with unprecedented new risks, challenges and even opportunities. As a
      major contributor to economic stability, the insurance industry must follow these
      trends very closely and develop scenarios to anticipate these events.

PMID- 14971090
TI  - Cardiac valvular tumors: cardiac papillary fibroelastoma.
AB  - Case histories of proposed life insurance are presented to introduce the topic of
      cardiac valvular tumors. Using fibroelastoma as the prototypical cardiac tumor,
      pathology, diagnosis, echocardiographic findings and clinical course are
      reviewed, based on available clinical literature. Although the natural history of
      benign cardiac tumors is uncertain, because of the risk of adverse outcomes,
      cases must be underwritten on an individual basis until long-term studies become
      available.

PMID- 14971091
TI  - Matters of the athletic heart.
AB  - Frequently an underwriter or medical director will question whether an increase
      in left ventricular mass represents pathologic left ventricular hypertrophy (LVH)
      or physiologic changes related to exercise. The LVH condition reflects end-organ
      damage related to abnormal hemodynamic stresses and confers an increased
      morbidity and mortality risk. When left ventricular mass is increased because of
      exercise, measured changes represent a normal, healthy cardiovascular system
      responding to the demands of that exercise. This article summarizes medical
      findings that distinguish pathologic LVH from an "athletic heart."

PMID- 14971092
TI  - Cost-benefit analysis of electron beam CT as a life insurance coronary disease
      risk assessment tool.
AB  - Electron beam CT (EBCT) or ultrafast CT is a diagnostic imaging technique that
      can identify calcium deposits within coronary arteries. Intra-coronary calcium is
      associated with coronary artery atherosclerosis. EBCT imaging has been advocated
      as a "better" way to screen for coronary artery disease. By producing a measure
      of the amount of calcium present, it may provide a non-invasive risk assessment
      tool that can predict the risk of future coronary events and death. Medical
      literature concerning identification and assessment of coronary risk using EBCT
      in the clinical setting is reviewed. The primary purpose is to illustrate one
      approach to a simple "back of the envelope" cost-benefit analysis (protective
      value) comparing EBCT with exercise electrocardiography as a life insurance
      coronary disease risk assessment tool. The performance and results of this
      analysis are contingent on a number of critical assumptions that are outlined in
      the text. The analysis limitations, and the future research required to refine
      the results are reviewed. With optimum levels of EBCT test performance, favorable
      thresholds of test costs, and long-term mortality data useful for assessment of
      value preservation, EBCT might prove to be a valuable risk assessment tool from a
      cost-benefit perspective under certain circumstances. Answers to key clinical
      research questions from prospective studies in asymptomatic cohorts are essential
      for refinement of a cost-benefit estimate.

PMID- 14971093
TI  - Cocaine revisited.
AB  - Insurance companies often test applicants for the presence of cocaine. Because a
      positive test may automatically preclude further consideration, such cases often
      never reach the medical director. The negative impact of cocaine use on
      insurability is reviewed.

PMID- 14971094
TI  - Assessment for congenital long QT syndrome.
AB  - A 29-year-old male presented for an evaluation of his risk for having congenital
      long QT syndrome. Despite being asymptomatic and having a normal QTc interval on
      the resting ECG, a suggestive family history was an indication for a thorough
      cardiac evaluation. A geneticist reviewed this workup and recommended against
      genetic testing. While up to 10% of affected carriers of a congenital long QT
      syndrome gene mutation can be asymptomatic with a normal QTc, consideration of
      all of the clinical factors allowed for further risk stratification. The
      evaluation of an ECG for the long QT syndrome includes calculating a corrected QT
      interval for the heart rate and assessing the T-waves for morphology associated
      with this syndrome.

PMID- 14971095
TI  - Problems in staging prostate cancer.

PMID- 14971096
TI  - Radiographic appearance of SARS.

PMID- 14971097
TI  - The ascent of wireless networks.

PMID- 14971098
TI  - Hospitals bring medical devices into the I.T. loop.

PMID- 14971099
TI  - Speech recognition is finding its voice.

PMID- 14971100
TI  - Down the beaten HIPAA path.

PMID- 14971101
TI  - Small hospitals have mighty I.T. plans.

PMID- 14971102
TI  - Some CIOs tired of making the same old requests.

PMID- 14971103
TI  - Small devices, big obstacles.

PMID- 14971104
TI  - Do mobile phones cause interference?

PMID- 14971105
TI  - Are subnotebooks the right fit?

PMID- 14971106
TI  - Pumped up about i.v. system.

PMID- 14971107
TI  - Embracing an image of the future.

PMID- 14971108
TI  - I.T. success doesn't come overnight.

PMID- 14971109
TI  - Data helps foretell customer needs.

PMID- 14971110
TI  - Making time for scheduling.

PMID- 14971111
TI  - Readers' perspectives. The Nov. 20 Institute of Medicine patient safety report
      advocating a national health information infrastructure.

PMID- 14971112
TI  - Pharmacogenetics, placebos and publication fraud.

PMID- 14971113
TI  - Claimed contemporary miracles.

PMID- 14971114
TI  - Corporate killing--will directors ever be held to account?

PMID- 14971115
TI  - Are doctors Good Samaritans?

PMID- 14971116
TI  - The legal minefield of occupational medicine: ambiguous or just complex?

PMID- 14971117
TI  - Infant vaccinations and childhood asthma among full-term infants.
AB  - PURPOSE: To determine if infant vaccinations are associated with childhood asthma
      among full-term infants. The secondary objective was to describe relationships
      between characteristics of infant wheezing and childhood asthma. METHODS: We used
      baseline data from a study of infant wheezing that selected full-term infants
      born into a health maintenance organization (HMO) during 1991-1994, continuously
      enrolled for at least 12 months and without perinatal pulmonary or other selected
      conditions. Information had been abstracted for infancy (0-18 months) regarding
      wheezing, vaccinations and asthma risk factors. Using automated data, we
      identified asthma cases in 1998 among those enrolled for at least 6 months during
      the year. RESULTS: A total of 1778 full-term infants met our study criterion and
      9% had asthma in 1998. Childhood asthma was not significantly associated with
      having received Hepatitis B vaccine or age at first Hepatitis B vaccine; number
      of whole-cell pertussis, Haemophilis influenzae type b or oral polio vaccine
      doses; having received measles, mumps, rubella vaccine; or total number of
      vaccine doses combined. Childhood asthma was significantly associated with number
      of infant wheezing episodes. CONCLUSIONS: Our findings do not support concerns
      that vaccines are associated with increased risk of asthma but confirm that
      frequency of infant wheezing is associated with childhood asthma.

PMID- 14971118
TI  - How well do patients report noncompliance with antihypertensive medications?: a
      comparison of self-report versus filled prescriptions.
AB  - PURPOSE: To address poor patient compliance with antihypertensives, clinicians
      and researchers need accurate measures of adherence with prescribed regimens.
      Although self-reports are often the only means available in routine practice,
      their accuracy and agreement with other data sources remain questionable.
      METHODS: A telephone survey was conducted on 200 hypertensive patients treated
      with a single antihypertensive agent in a large health maintenance organization
      (HMO) or a Veterans Affairs medical center (VAMC) to obtain self-reports of the
      frequency of missing antihypertensive therapy. We then analyzed records of all
      filled prescriptions to calculate the number of days that patients actually had
      antihypertensive medications available for use. Agreement between the two data
      sources was measured with correlation coefficients and kappa statistics. Logistic
      regression models were used to identify demographic, clinical and psychosocial
      correlates of overstating compliance. RESULTS: There was very poor agreement
      between self-reported compliance and days actually covered by filled
      prescriptions (Spearman correlation coefficient = 0.15; 95%CI: 0.01, 0.28). Very
      poor agreement was also observed between a categorical measure of self-reported
      compliance (ever vs. never missing a dose) and categories of actual compliance
      defined by filled prescriptions (< 80% vs > 80% of days covered; kappa = 0.12,
      95%CI: -0.02, 0.26). Surprisingly, few factors were associated with inaccurate
      self-reporting in either crude or adjusted analyses; fewer visits to health care
      providers was significantly associated with overstating compliance. CONCLUSIONS:
      Compliance was markedly overstated in this sample of patients and few
      characteristics identified those who reported more versus less accurately.
      Clinicians and researchers who rely on self-reports should be aware of these
      limits and should take steps to enhance their accuracy.

PMID- 14971119
TI  - Diagnosis and treatment of gastroesophageal reflux disease in Ohio Medicaid
      patients: practice patterns and temporal trends.
AB  - PURPOSE: There is a paucity of data about the use of procedures and prescription
      medications in the treatment of gastroesophageal reflux disease (GERD) in actual
      clinical practice. METHODS: Outpatient Ohio Medicaid claims from 1994 to 1998
      were searched to identify patients with an initial diagnosis of GERD along with
      associated prescriptions and gastrointestinal procedures. Complications of GERD
      and comorbid illnesses were also determined. RESULTS: A total of 5579 patients
      were identified. Histamine-2 receptor antagonists (H2RA's) were prescribed in
      59%, followed by proton pump inhibitors (PPI's) (30%) and prokinetic drugs (17%).
      PPI's were more frequently prescribed to patients with GERD-related
      complications, peptic ulcer disease and major comorbidities, and patients who
      received PPI's were also more likely to undergo upper gastrointestinal endoscopy.
      The frequencies of upper endoscopy and barium studies were 20% and 11%
      respectively, with no change over the study period. There was an increased
      frequency of PPI therapy (17-43%) and decreased frequency of H2RA therapy (72
      47%) from 1994 to 1998 which persisted after adjusting for potential differences
      in case mix. CONCLUSIONS: In this population-based study, prescription of PPI's
      increased over time which likely reflected changes in clinician practice rather
      than patient mix. Despite a greater awareness of GERD complications, use of upper
      endoscopy did not increase. Although the cohort consists of predominantly low
      socioeconomic status, female patients, further studies should be conducted in
      other populations to confirm these findings.

PMID- 14971120
TI  - The risk of esophageal obstruction associated with an anti-allergy medication
      (Claritin-D 24-Hour--original formulation).
AB  - PURPOSE: To investigate a possible increased risk of esophageal obstruction among
      users of loratadine and pseudoephedrine (Claritin-D 24-Hour [C-D 24], the
      original, round, extended-release formulation) compared to two other tablet
      formulations of loratadine. METHODS: Pharmacy data of 12 managed care plans were
      screened to identify users in the three groups from 1 September 1996 to 31
      December 1998. Users with a medical claim following their first loratadine
      prescription (Index prescription) indicating an esophageal obstruction or
      endoscopic procedure were considered claims-identified cases. Medical records
      were reviewed to validate case status. RESULTS: There were 233,901 users (61%
      female) and 245 claims-identified cases occurring within 30 days after the first
      prescription. The incidence rate per 10,000 users of claims-identified cases
      occurring on the Index prescription date was higher among C-D 24 users (IR = 1.4)
      than Claritin Regular (C-R) users (IR = 0.07; p < 0.002) or Claritin-D 12-Hour (C
      D 12) users (IR = 0.3; p > 0.05). Medical record review of 15 claims-identified
      cases confirmed two cases of acute esophageal obstruction, both among C-D 24
      users. CONCLUSIONS: Claims-based analysis suggested an increased risk of
      endoscopic procedures on the Index date among C-D 24 users compared to C-R users.
      However, after medical record review, the study did not provide conclusive
      evidence of an association between C-D 24 use and esophageal obstruction. This
      study highlights the importance of validating findings from claims data using
      medical records.

PMID- 14971121
TI  - Ovarian cancer risk and use of phenolphthalein-containing laxatives.
AB  - PURPOSE: Experimental studies in rodents demonstrated the carcinogenic potential
      of phenolphthalein, the active ingredient in some laxatives, administered at
      doses similar to the dose that could be used by humans. Ovarian cancer was one of
      the cancers observed in these studies. We examined the association between
      epithelial ovarian cancer and use of phenolphthalein-containing laxatives in a
      population-based case-control study. METHODS: The study includes 356 epithelial
      ovarian cancer cases (256 invasive, 100 borderline) and 424 controls. Cases were
      identified through a population-based registry in Los Angeles County in 1992
      1998, and controls were matched to cases by age, race/ethnicity and neighborhood.
      Data on laxative use (specific brands, frequency of use, usual dose) were
      obtained by structured in-person interview. RESULTS: Compared to women who never
      used a laxative, ever use of a phenolphthalein-containing laxative was not
      associated with an increased risk of invasive ovarian cancer (odds ratio (OR)
      1.1, 95% confidence interval (CI) 0.75, 1.5) or of borderline ovarian cancer (OR
      0.75, 95%CI 0.37, 1.5). Total days used, mean number of pills per day and
      cumulative dose were also unrelated to risk. CONCLUSIONS: This study provides
      some assurance that phenolphthalein-containing laxatives do not increase the risk
      of ovarian cancer in humans. These findings are of particular importance to those
      countries in which phenolphthalein is still used in over-the-counter medications.

PMID- 14971123
TI  - Pharmacoepidemiology and drug safety.

PMID- 14971122
TI  - Reduction in the therapeutic intensity of abortive migraine drug use during ACE
      inhibition therapy--a pilot study.
AB  - INTRODUCTION: Since a few case reports have demonstrated some beneficial effects
      of angiotensin converting enzyme (ACE) inhibitors in migraine prevention, we were
      interested in studying the impact of ACE inhibitors and angiotensin II receptor
      antagonists (Ang II) on the consumption of specific abortive migraine drugs and,
      therefore, indirectly on the frequency of migraine attacks. METHODS: Data from a
      large prescription database involving 95 patients initiating a specific abortive
      migraine drug (ergotamine or a triptan) and subsequently treated with either an
      ACE inhibitor or angiotensin receptor antagonist (index group: ACE/Ang II) or
      diuretic (reference group) were analysed. The effects of ACE/Ang II inhibition as
      well as diuretic therapy on reducing the frequency of migraine attacks were
      assessed by measuring the mean consumption of abortive migraine drug use, in DDDs
      per month ('therapeutic intensity'), before, during and after ACE/Ang II or
      diuretic therapy. A 'therapeutic fluctuation intensity estimate' of abortive
      migraine drug use for all patients was likewise calculated. RESULTS: On an
      individual level, the therapeutic intensity (TI) fluctuation estimate, 'during'
      relative to 'before' ACE diuretic therapy, was significantly larger for the
      ACE/Ang II group (62% reduction) than for the diuretic group (24% reduction) (p =
      0.02). For patients who continued abortive migraine drug use during and after
      ACE/Ang II or diuretic therapy, a significantly larger reduction in this estimate
      was observed during ACE/Ang II inhibition (68.9%) compared to during diuretic
      therapy (10.5% increase) (p = 0.004). The TI fluctuation estimate, after relative
      to 'during', had increased by 50.3% after ACE/Ang II inhibition and had reduced
      by 22.2% after diuretic treatment (p = 0.1). CONCLUSIONS: A clear reduction in
      the TI of abortive migraine drug use during the use of ACE inhibitors as compared
      to diuretic treatment was observed. Our findings may indirectly support a
      positive effect of ACE/Ang II inhibition on the frequency and severity of
      migraine attacks, as observed in other studies and reports.

PMID- 14971124
TI  - The structural reform of mental health services.
AB  - During past decades many countries have initiated extensive mental health care
      system reforms, and the main goal of these reforms has been the transfer of
      treatment of the mentally ill from psychiatric hospitals to the community. For
      example, assessment of the results of these reforms in Italy and Austria
      demonstrates considerable reduction in the number of psychiatric beds, higher
      quality and more available community services, and increased total expenditure
      for mental health services. However, because sufficient data is not yet
      available, many questions regarding how these reforms impact improvement in
      patient clinical parameters remain unanswered. Some of the answers to these
      questions can be gleaned from the results of research carried out in the United
      States and Canada in the 1980s. This research evaluated transfer of psychiatric
      treatment from a hospital setting to a community service setting. The results
      demonstrated that community treatment models were more effective than a hospital
      treatment model in reducing the number of hospitalizations and shortening length
      of stay. Patient monitoring also demonstrated good integration into the
      community. However, alongside the research supporting these reforms, there is
      some research that demonstrates a number of possible disadvantages: an increase
      in the number of homeless and in the mortality rate among psychiatric patients,
      and an increase in rehospitalization rates of chronically ill patients," referred
      to as the "Revolving Door Syndrome." To avoid the disadvantages that could
      possibly accompany the reform, particular attention needs to be given to planning
      and funding, so that development of community services and reduction in
      psychiatric hospital system correspond. Care must be taken to ensure that the
      number and the geographic location of these services meets the need of the
      population at risk, and that staff is available and well trained. A monitoring
      system should be set in place to monitor the patients according to the clinical
      standards agreed upon, and at the same time guidelines should be set up to
      evaluate the functioning of community services. The structural reform is
      progressing and should be completed at the end of 2005. However, development of
      community services is not progressing at the desired rate. In January 2003, the
      Israeli government made a decision to transfer the responsibility for medical
      insurance for the mentally ill from the government to the Sick Funds. However, an
      agreement between the Ministry of Health, the Ministry of the Treasury and the
      Sick Funds has yet to be signed and the government's decision has yet to be
      realized. This has caused development of community services to come to a halt,
      and neither the government nor the Sick Funds are investing in community
      development. We can only hope that the transfer of responsibility for health
      insurance for the mentally ill from the State to the Sick Funds will be completed
      soon and that development of community service for the mentally ill will then
      move forward quickly.

PMID- 14971125
TI  - Reduction in inpatient length of stay and changes in mental health care in Israel
      over four decades: a national case register study.
AB  - BACKGROUND: The purpose of the present study was to investigate trends over the
      past 40 years in the accumulated length of hospital stay, and to consider how
      these trends might have been affected by changes in the provision of mental
      health care in Israel from 1960 to 1997. METHODS: The national psychiatric case
      register was used to follow four cohorts of all new admissions in 1960, 1970,
      1980 and 1990 diagnosed with schizophrenia or affective disorders for the first
      seven years following the index admission. RESULTS: Most of the changes in length
      of stay occurred among patients with schizophrenia. The overall accumulated
      length of stay decreased by 50% between 1960 and 1980. The largest reduction was
      observed among long-stay patients with schizophrenia. Number of admissions did
      not change for the four cohorts. LIMITATIONS: The interpretation of the data
      remains speculative, as we are attempting to establish causality between parallel
      trends. CONCLUSIONS: The general trend in the findings of this study corresponds
      with changes that took place between 1970 and 1990 in the outpatient care for the
      mentally ill. These innovations facilitated the discharge of patients with
      chronic schizophrenia and altered the case mix of the newly admitted patients.

PMID- 14971126
TI  - Was it a good move? Improvement in quality of life among chronic mental patients
      moving from a mental hospital to a hostel in the community.
AB  - BACKGROUND: This study examined whether transition from hospital to hostel
      improves patients' quality of life (QOL). METHOD: In a longitudinal prospective
      study comparing the QOL of 16 patients who moved to a hostel with that of 20 who
      remained hospitalized, we posited that the former would exhibit improved QOL. We
      also assessed the reliability of psychiatric patients' reports by comparing them
      with staff reports. RESULTS: No changes were reported in the QOL of hospitalized
      patients, whereas those who moved to the hostel exhibited significant improvement
      in all aspects of life, as reflected in the World Health Organizations Quality of
      Life measure (WHOQOL-BREF), reports by patients and staff and subjective (but not
      objective) indicators in the TL30s questionnaire. Patients' reports reflect a
      higher QOL improvement than staff reports but both display similar trends
      regarding changes in QOL. CONCLUSIONS: It was concluded that the move from the
      hospital to the hostel improved the QOL of the patients.

PMID- 14971127
TI  - Relationship of clinical and demographic characteristics of schizophrenia
      patients to rehabilitation status.
AB  - OBJECTIVES: To identify the relationship between demographic, clinical and
      treatment variables and measures of psychiatric rehabilitation status among
      chronic schizophrenia patients residing in rehabilitation hostels in the
      community. METHOD: Demographic and clinical data were collected from a sample of
      89 patients. The data included: age, gender, education, origin immigration
      status, age of onset of the illness, family history of mental illness, early
      parental loss status, psychiatric symptoms (measured by the Brief Psychiatric
      Rating Scale) and compliance with medication. Rehabilitation status was assessed
      by using 5 measures extracted from the Wisconsin Quality of Life-Provider
      Questionnaire: occupational activities, social relations and social support,
      activities of daily living, mean days of readmission and recidivism. RESULTS:
      Psychiatric symptoms, drug compliance and the age of the patient were the only
      variables that were correlated with the rehabilitation measures. The symptoms
      showed a robust relationship with all five measures, drug compliance was highly
      correlated with the occupational activities, social relations/social support and
      activities of daily living measures and the age of the patient correlated with
      the social relations/social supportand activities of daily living measures. Drug
      compliance was also correlated with the symptoms. CONCLUSIONS: The results
      indicate that older patients, patients with more profound psychiatric symptoms
      and patients who do not comply with medication manifest a lower rehabilitation
      status. While these factors may seem self-evident in the clinical environment,
      they might be overlooked in the community environment and make rehabilitation
      less efficient.

PMID- 14971128
TI  - Should patients with chronic psychiatric disorders remain in hospital? Results
      from a service inquiry.
AB  - The pattern of mental health care in Israel is undergoing major reform. In this
      report we explored hospitalization rates of 1,448 former long-stay psychiatric
      inpatients (70% of them with ICD-10 diagnosis of schizophrenia) subsequent to
      their transfer from countrywide psychiatric hospitals to 57 community-based
      hostels or alternative community settings between the years 1996-1999. Using data
      from the National Psychiatric Case Registry and a mirror image design, we
      examined the rates of readmission and calculated the number of saved hospital
      days during the community residence period, which compares more than two and four
      years, respectively, for 80% and 48% residents. T-tests, Mann-Whitney tests and
      analysis of variance were performed to examine differences in hospitalization
      rates and associated variables. Results showed that a minority, 36.2% of the
      former inpatients, was readmitted during their hostel residence. In comparison
      with an equivalent pre-hostel period, the time spent in hospital for those hostel
      residents that needed readmission was significantly shorter and the related day
      savings were considerably higher. The rehospitalized residents tended to be
      younger at their first hospitalization and at referral to the hostels, compared
      to those nonhospitalized. In addition, age by gender interaction, and length of
      hostel residence affected readmission rates. We may conclude that the policy
      decision to move the inpatients to a community setting is supported by the fact
      that the majority of the hostel residents was able to stay away from
      hospitalization.

PMID- 14971129
TI  - System flexibility in the rehabilitation process of mentally disabled persons in
      a hostel that bridges between the hospital and the community.
AB  - BACKGROUND: Deinstitutionalization and community mental health services have
      become the focus of mental health care in the United States, Italy and England,
      and now in Israel. METHODS: Tirat Carmel MHC developed an intervention model of
      organizational change implemented in a rehabilitation hostel. It is an interim
      service based on graduated transition from maintenance care to a transitional
      Half-way House, followed by a Transitional Living Skills Center oriented for
      independent community living. RESULTS: Of 205 rehabilitees who resided in the
      hostel since the beginning of the project, 138 were discharged to community
      residential settings: 67 patients were discharged to reinforced community
      hostels; 27 to sheltered housing and 23 to independent residential quarters; 7
      patients were discharged to comprehensive hostels, 3 to old-age homes and 11
      returned home to their families. In terms of employment, 79 were placed in
      sheltered employment facilities, 24 work in the open market and 3 returned to
      school; 22 work in therapeutic occupational settings and 10 patients discharged
      to comprehensive hostels and old-age homes are engaged in sheltered employment
      programs in those settings. CONCLUSION: The system flexibility model and the
      rehabilitation processes anchored in normalization supported the relocation of
      hospitalized psychiatric patients to community-based settings and enabled the
      rehabilitees to cope with readjustment to community life.

PMID- 14971130
TI  - Knowledge and attitudes about mental disorders among principals of adult
      education schools.
AB  - BACKGROUND: The Ministry of Health is stepping up its efforts to both reduce the
      inpatient psychiatric population and enable former inmates to become fully
      reintegrated into society. The latter aim includes the provision of formal
      education for those with mental disorders who did not complete a full cycle of
      schooling. Stigma and discrimination at school may lead to the failure of this
      program. OBJECTIVE: To explore the knowledge and attitudes of the principals of
      schools for adult education towards mental illness and persons with mental
      disorders. METHOD: Almost all countrywide school principals (93.8%, n = 76) were
      interviewed by telephone using a short questionnaire of 16 items tapping their
      knowledge and attitudes. Frequency distributions, Chi-square and t-tests were
      used to analyze the data. RESULTS: The school principals were able to mention a
      fewer number of mental disorders in contrast to medical conditions, used as
      reference criteria. They recognized psychosis but not depression as a mental
      disorder. Their attitudes revealed an ambivalent approach to the person with a
      mental disorder, including those that are students. Higher level of academic
      education was associated with positive attitudes, while personal familiarity with
      a mentally disturbed person was slightly associated with more positive school
      related attitudes. CONCLUSIONS: The results suggest a "case for action": programs
      to enhance mental health knowledge and foster more positive attitudes among
      school principals would seem to be needed. This would better assure the
      integration of the former inpatient into the adult education system.

PMID- 14971131
TI  - Effect of transfer of long-stay psychiatric inpatients from hospital to hospital.
AB  - BACKGROUND: Chronic psychiatric patients hospitalized in institutions about to be
      closed are not always fit to be transferred to community-based facilities. The
      purpose of our study was to investigate how the mental health of a group of such
      patients was affected by their being transferred to another hospital. METHODS:
      202 patients were evaluated prior to transfer and six months after the transfer,
      by means of the Clinical Global Impression (CGI), the World Health Organization
      (WHO) Disability Scale and the Nurses' Observation Scale for Inpatient Evaluation
      (NOSIE). RESULTS: On the CGI, half the patients showed evidence of improvement
      while only 4% seemed to deteriorate. For the NOSIE and WHO Disability Scale,
      improvement of scores was similarly more common than deterioration. Factors that
      correlated with improvement included male sex, younger age, and a shorter
      hospital stay. LIMITATIONS: This is a naturalistic study of the effects of
      transfer which does not include a control group. CONCLUSION: Institutional
      transfer of psychiatric patients can be carried out without harm to the patient's
      welfare, and may even be beneficial.

PMID- 14971132
TI  - Demographic, clinical and treatment characteristics among Meuhedet sick fund
      mental health referrals.
AB  - INTRODUCTION: The role of the sick funds in the delivery of mental health
      outpatient services is expected to increase in Israel in the near future.
      Consequently there is an urgent need for assessing relevant parameters of the
      patient populations and treatment patterns presently characterizing sick fund's
      mental health delivery frameworks. METHOD: During a random census month all
      patients who referred to Kupat Holim Meuhedet mental health services in Jerusalem
      district completed structured questionnaires including demographic, medical and
      mental health history data, and the Symptom Checklist 90 (SCL-90). The
      professionals who performed the screening assessments filled in a structured
      questionnaire referring to clinical status parameters, diagnosis and treatment
      decisions. RESULTS: Eighty-three new referrals were screened during the period
      studied, out of which 54 (65%) were absorbed within the treatment framework of
      the sick fund. Women patients were twice as numerous as men. The sample was
      heterogeneous in terms of demographic characteristics and included relatively
      high rates of recent physical injury and medical hospitalization. Only
      approximately 10% of the patients had been referred by their family doctor and
      only approximately 3% had psychotic disorders. The symptom profile reported was
      characterized by mild to moderate severity and the most common DSM-IV diagnoses
      made were depressive, anxiety adjustment and personality disorders. About 50% of
      the sample was recommended individual psychotherapy and though not mutually
      exclusive approximately 40% psychotropic medication. LIMITATIONS: Relatively
      small sample size and catchment area. Before generalization of the findings,
      larger scale studies are warranted. CONCLUSIONS: This pilot study offers a
      rigorous examination of the content of care of a small sick fund mental health
      delivery system. Our findings may be instrumental in the development of new
      services and adaptations to changes in mental health policies.

PMID- 14971133
TI  - The forensic psychiatry corner.

PMID- 14971134
TI  - [Predictive clinical factors of extracapsular extension in lymph nodes of the
      neck].
AB  - In order to assess the main clinical factors predicting extracapsular spread
      (ECS) in neck lymph nodes of patients with laryngeal cancer, step-wise logistic
      regression (LR) was applied to data retrospectively obtained from 141 patients
      surgically treated. Thirty six variables were evaluated in each patient. One
      hundred twenty eight out of the 141 patients had complete information on the 36
      variables studied. With data from these 128 patients a linear discriminant
      function was obtained with an overall accuracy of 65.4%. The rate of correct
      prediction was 60.8% for presence of ECS and 71.7% for absence of ECS. Only 3
      secondary variables created out of the 36 employed for the analysis were
      necessary to obtain these results.

PMID- 14971135
TI  - [Surgical treatment of Graves-Basedow disease. Descriptive study and review of
      the literature].
AB  - Graves-Basedow's disease is an autoimmune pathology that causes a clinical
      hyperthyroidism which has a medical treatment at first place. However, the
      surgery has indications and obtains good results generally. We report a
      descriptive study about 35 patients (27 female and 8 male) sent for a surgical
      treatment by Endocrinology. We have analysed several variables: Family
      antecedents, clinical symptoms, Scintigraphy results, FNAB results, type of
      intervention, pathologic anatomy (PA) and complications after the surgery. We
      have performed a literature review and thought that Total Thyroidectomy (TT) is
      the technique of choice for surgical treatment of Graves' disease instead of
      Subtotal Thyroidectomy (ST) suggested by some authors.

PMID- 14971136
TI  - [Peritonsillar phlegmons and abscesses. Retrospective study of 100 cases].
AB  - Our main goal was performing a retrospective study about peritonsillar cellulitis
      and abscess to prove the efficiency of treatment. So that we have collected 100
      clinical histories of admitted patients in our ENT Service between 1990 and 2001
      with such pathology and analysed a serie of variables and the treatment given in
      each case. It is one of the most common infectious diseases of the head and neck
      region. If aspiration positive, it require an incision and drainage to improve
      the symptoms (throat pain, fever, dysphagia and trismus). We have made no
      immediate tonsillectomies. All the patients were hospitalized and average stay
      was 3 days. 21 patients were re-admitted because of a recurrence pathology before
      the later programmed surgery.

PMID- 14971137
TI  - [Malignant tumors of the parotid gland].
AB  - We review patients operated of parotidectomy in our ENT department of Dr. Peset
      Hospital from Valencia during the period 1975-2001. We sheltered an amount of 147
      cases. The pathologic distribution between benign and malign tumors was as
      following: 121 benign tumors (83%) and 26 malign tumors (17%). Here we study
      malign parotid tumors, which represent 17% of total parotid tumors. Sensibility
      and specificity of FNA was 54% and 96.5% respectively. We performed almost with
      similar frequencies total and suprafacial parotidectomies in 46% and 42% of cases
      respectively. Total parotidectomy with facial resection is indicated in cases
      with tumor nerve infiltration and has been done in 8% of cases. The main
      complications of surgery were facial nerve dysfunction and Frey syndrome.
      Permanent facial nerve dysfunction and and transitory facial nerve disfunction
      occurred in 3.8% and 30.8% of patients respectively. Frey syndrome appeared in
      10% of patients operated of parotidectomy. Recurrences occurred in 15.4% of
      patients.

PMID- 14971138
TI  - [Neuroendocrine carcinoma of the nasal fossa. An independent entity?].
AB  - We present one case of a neuroendocrine carcinoma of nasal fossa and paranasal
      sinuses, of aggressive behavior, which has been controlled with chemo
      radiotherapy after a double postsurgical recurrence. We do a literature revision
      emphasizing the anatomopathologic differentiation of these tumors with the
      olfactory neuroblastomas, and the therapeutic controversies in advanced stages.

PMID- 14971139
TI  - [Efficacy of the treatment of Meniere's disease with oligoelements].
AB  - OBJECTIVES: 1st To study and know better the therapeutical action of the
      olygoelements in the Meniere's diseases. 2nd To analyse if there are
      significative statistical associations of therapeutical response to the
      olygoelements in the Meniere's sickness. MATERIAL AND METHODS: We make a design
      of observational study of 68 patients with the diagnostic of Meniere's sickness,
      with classical therapeutic and 34 treated with and without litium olygoelements
      and manganese&cupper. RESULTS: In the descriptive statistics we find better
      results in the Menieres treated with olygoelements than in those that were not
      treated. In the analytic associative statistics we find that for 3 degrees of
      freedom a chi-square of 13.20 that is equal to 0.00459 (less than 0.05) that
      indicate that there's significative differences between both treatments not due
      to casuality. DISCUSSION: There are significative differences of better results
      in Menieres treated with olygoelements. The new aspect of potentiate the
      therapeutical arsenal of Menieres evidences a new possibility of soon clinical
      aplication.

PMID- 14971140
TI  - [Complications of thyroid and parathyroid surgery. Retrospective study and review
      of the literature].
AB  - The number of ORL surgeons performing thyroid and parathyroid glands
      interventions is increasing more. Most of these surgeries are successful for us
      and our patients specially. However, this kind of operation can result in
      complications such as hypocalcemia and recurrential palsy, transitory or
      permanent, that it is necessary to know and avoid as far as possible. We are
      reporting a retrospective study of 12 years, based on our personal experience,
      where the real complications are analysed in 615 operated patients (500 with
      thyroid pathology and other 115 with parathyroid affectation) and after a
      comparation between both groups. The percentages of hypocalcemias were 25.6% and
      24.3%, respectively. While in thyroid surgery (TS) the recurrential palsies
      showed a 6.6%, in parathyroid surgery (PS) were 0.8% only. The anatomical
      embriologic knowledge, meticulousness and experience are three main qualities
      that are able to reduce the number of complications in the surgery of thyroid and
      parathyroid glands.

PMID- 14971141
TI  - [Surgery of otosclerosis. Retrospective study and review of the literature].
AB  - Between 1990 and 1996 we have operated 134 patients with otosclerosis. 91 were
      female and 43 male with 42 years average. We report a retrospective study and
      collect a string of clinical preoperative variables analysing the kind of surgery
      performed with the findings and most relevant technical difficulties,
      complications and hearing improvement obtained just after the operation and one
      month later. Stapedectomy or stapedotomy have given good results in our serie
      with significant hearing recuperation on more than 90% of the cases well selected
      and operated by first time.

PMID- 14971142
TI  - [25 years of the health reform 833].

PMID- 14971143
TI  - [Complications in newborns treated with nasal CPAP (continuous positive airway
      pressure) in second level neonatal disease].
AB  - After the introduction of Nasal Continuous Positive Airways Pressure (nCPAP) in a
      neonatal intensive care unit, the incidence of complications and outcomes of
      newborns was explored. The clinical and nursing records of 64 newborns treated
      with O2 and Hood's cuff (January 1996-June 1999) were compared to those of 68
      patients treated with nCPAP (July 1999-July 2002). Newborns < 32 weeks, with
      congenital abnormalities and major myocardiopathies were excluded. The two groups
      were comparable for the main characteristics. Newborns treated with nCPAP needed
      less intubations (7 vs 14, p 0.004) and had less transferrals to more specialised
      structures (12 vs 26, p 0.001). The number of complications is comparable with
      the exception of a larger number of desaturations in the nCPAP group (20 vs 5, p
      0.001) that anyhow, did not require resuscitation. The nCPAP allowed a reduction
      of the number of intubations and therefore newborns could be cared for in our
      centre, thus reducing the disadvantage of a transferral to a more specialised
      centre. This advantage, associated to the comparable number of complications, may
      be attributable to the short duration of the treatment but also to the attentive
      and appropriate nursing care.

PMID- 14971144
TI  - [Relatives of hospitalized geriatric patients: their needs of information,
      counseling, and access].
AB  - The perception of needs of relatives of patients admitted to geriatric units was
      investigated by interviewing 70 relatives of patients admitted to the geriatric
      ward of Verona hospital, over 45 consecutive days. The self compiled
      questionnaire used for the survey included a list of 22 potential needs referring
      to three categories: information, counselling and accessibility. Relatives were
      asked to rate them, on a scale from 1 to 4, according to the perceived priority
      and level of satisfaction. The relatives rank as most important the information
      need: the need of receiving information on the illness and its' course; of being
      contacted and informed on every clinically relevant change in health-illness
      status and being sure that the patient receives the best possible care. The level
      of satisfaction for information, counselling and accessibility is low. The
      perception of needs is influenced by the level of education or the relative.

PMID- 14971145
TI  - [Self administration of oral medications in hospitalized patients with orthopedic
      traumatology conditions].
AB  - Self administration of drugs is the exception in hospitalized patients, even if
      an increasing body of literature shows the advantages of this practice. The aim
      of the study was to identify criteria for selecting patients able to self
      administer their drugs, and assess their number. Six focus groups with nurses of
      orthopaedic wards were organised to identify the main criteria for selecting
      patients. The criteria were: no severe disabilities, reliable (according to the
      nurses' judgement); willing to do so; able to swallow; spatially and temporally
      oriented; able to learn; already self-administering drugs at home. In a one day
      prevalence survey over 112 patients prescribed oral drugs 58% were considered
      eligible for self administration. The more relevant criterion was the
      reliability. If nurses allowed the eligible patients to self administer drugs
      they could save 70 minutes/day to spend in informing patients on their drug
      therapies.

PMID- 14971146
TI  - [Prescriptions profile of the elderly population].

PMID- 14971147
TI  - [Pre- and postoperative care for patients].

PMID- 14971148
TI  - [Tumor necrosis factor alpha in systemic scleroderma].
AB  - The authors present the review of the literature on the role of tumor necrosis
      factor alpha (TNF alpha) in scleroderma systematica (SS). It is shown that TNF
      alpha participates in activation of vascular endothelium, regulation of immune
      response and metabolism of the connective tissue by modulation of fibroblastic
      function. SS patients exhibit a systemic and local rise of TNF alpha content.
      This rise contributes to SS progression, development of fibrosing alveolitis and
      skin fibrous alterations in Raynaud's syndrome.

PMID- 14971149
TI  - [Current views of the pathogenesis of irritable bowel syndrome].
AB  - Three main trends in pathogenesis of irritable bowel syndrome are considered:
      dysfunction of psychic activity with associated changes in vegetative functions
      and humoral reactions, visceral hypersensitivity, abnormal intestinal motility.
      Morphological manifestations of the syndrome are also outlined.

PMID- 14971150
TI  - [Positron-emission tomography in oncology].
AB  - This review analyses clinical results, new trends and recommendations of the
      leading medical centers concerning application of positron-emission tomography
      (PET) with F-18 fluorodeoxyglucose (F18 FDG) in cancer patients. This method of
      radionuclide visualization has been widely introduced for the last decade in
      diagnosis of cancer of unknown primary location, or CUP-syndrome, bronchogenic
      cancer of the lungs, cancer of the head and neck, malignant lymphoma and
      melanoma, colorectal and neuroendocrine cancer. Efficacy of this procedure,
      physiological grounds, performance are considered. Potentialities of F18 FDG PET
      are demonstrated in tumor screening, detection of metastases, recurrences after
      surgical, radiation or drug antitumor treatment or monitoring. In combination
      with CT, MRT, USI and other techniques, F18 FDG PET raises accuracy of the
      diagnosis of pathological changes at any stage of cancer with resulting
      improvement in further therapeutic and follow-up efficacy.

PMID- 14971151
TI  - [Effects of adaptation to intermittent normobaric hypoxia on the results of 24
      hour monitoring of arterial pressure in hypertensive patients].
AB  - 30 hypertensive patients of the study group received combined therapy including
      adaptation to intermittent normobaric hypoxia and medicines. 32 control
      hypertensive patients were treated with drugs alone. 24-h monitoring of blood
      pressure (BP) in all the patients has shown that the study group achieved a more
      pronounced lowering of AP, especially of maximal AP nocturnal and diurnal rises.
      The combined therapy normalized 24-h AP profile, it increased the number of
      patients with an adequate fall of nocturnal AP while the number and duration of
      high AP episodes decreased. Positive changes in a 24-h AP profile were
      significantly more evident in patients of the study group than in patients
      treated only with hypotensive drugs.

PMID- 14971152
TI  - [Primary acute rheumatic fever in juveniles from an organized community].
AB  - A closed population of juveniles was studied to follow-up manifestations of
      primary rheumatic fever. In line with other unfavourable factors, the onset of
      the disease within the first 6 months of the observation was due to cross
      streptococcal infection (foci of chronic nasopharyngeal infection were detected
      in 68.6% examinees, rheumatism debut after acute nasopharyngeal infection was in
      91.0% patients). Persistence of streptococci was established in many blood counts
      in immunofluorescence reaction in 88.2% patients in acute disease, in more
      patients with lingering rheumatic process. Clinical manifestations include, aside
      from arthritis and rheumocarditis, frequent thyroid and gastrointestinal lesions.
      It is thought valid to raise the dose and duration of administration of
      penicillin in patients with primary rheumatic fever as it eradicates chronic
      infection foci, prevents recurrences, reduces the number of patients with a
      lingering course of the disease, with recurrences and valvular defects of the
      heart.

PMID- 14971153
TI  - [Antiphospholipid activity of the blood in patients with ischemic heart disease
      and thrombogenic complications].
AB  - The authors propose a method of estimating antiphospholipid activity of blood by
      phospholipids (PL) assays in circulating immune complexes (CIC). Screening of PL
      in CIC is an additional test in examination of patients with ischemic heart
      disease associated with thrombogenic complications and suspected antiphospholipid
      syndrome.

PMID- 14971154
TI  - [Multifocal atherosclerosis in patients with ischemic heart disease].
AB  - Combined atherosclerotic involvement of the brachiocephalic arteries (BCA) and
      lower limb arteries has been analysed in 107 patients (56 females and 51 males)
      with a verified diagnosis of ischemic heart disease (IHD). BCA atherosclerosis
      was detected in 83.9% females and 93.1% males. 75.8% examinees had no murmur. It
      is suggested that arterial hypertension and obesity in females with IHD may be
      risk factors of BCA kinking. Frequency of combined affection of extracranial
      arteries and lower limb arteries reached 23.2% females and 96% males. Therefore,
      it is necessary to screen these arteries for atherosclerosis in all IHD patients.

PMID- 14971155
TI  - [Autonomic regulation and emotional status in patients with ischemic heart
      disease having pain syndrome of various severity].
AB  - To study vegetative regulation and emotional status of ischemic heart disease
      (IHD) patients with various pain severity, 81 patients with IHD were examined.
      Personality characteristics were studied by the data of MMPI questionnaire,
      reactive and personal anxiety--of Spilberger questionnaire, depressive changes-
      of Beck's questionnaire, vegetative status--by vegetative discharge, Seattle
      angina questionnaire of life quality, heart rhythm variability and cardiovascular
      tests. All the patients have undergone clinical examination, exercise stress
      tests, echocardiography. Selective coronary angiography was made in some
      examinees. The patients were divided into two groups by anginal pain severity.
      The patients with more severe anginal pain had higher reactive and personal
      anxiety, neurotization. This was not associated with changes in the vegetative
      status and hemodynamics at rest. The detected emotional disorders in IHD patients
      may cause higher sensitivity of these patients to pain, on the one side, and
      changes in vegetative regulation of cardiovascular system and hemodynamics, on
      the other.

PMID- 14971156
TI  - [Postoperative course of ischemic heart disease in patients with various
      reconstructive procedures on the coronary vessels].
AB  - The study was aimed at evaluation of a clinicofunctional condition of patients
      with ischemic heart disease (IHD) operated on the coronary vessels as well as
      features of postoperative course of the disease to design relevant therapeutic
      and prophylactic measures. The analysis was made of rehabilitation and long-term
      (up to 60 months) outcomes of cardiosurgical operations. Features of
      rehabilitation were studied in groups of patients after coronary artery bypass
      grafting (CABG), creation of a mammarocoronary bypass combined with CABG and
      transcutaneous transluminal coronary angioplasty. To assess the results of
      cardiovascular patients rehabilitation, to study long-term results of
      cardiosurgical operations and compare conditions of patients after different
      cardiac operations, the parameter of "double product" is proposed under loading
      of 50 W. Three periods of postoperative run of the disease were identified:
      improvement with maximal physical performance of the patient,
      clinicopsychological stabilization, functional depletion and development of IHD
      complications.

PMID- 14971157
TI  - [Effect of adrenergic and histaminergic disorders on the subclinical course of
      atopic bronchial asthma].
AB  - To characterize membrane-receptor peculiarities of the adrenergic and
      histaminergic systems under the model of peroxide and hyperosmolar effect in
      atopic bronchial asthma (ABA) and preclinical stage of BA, we have examined 25
      patients with ABA, 19 patients with nonpulmonary allergy, 28 healthy men and 21
      healthy blood relatives of ABA patients. The phenomenon of inversion of the
      effect of beta-adrenoblocker (obzidan) and of the combined effect of histamine
      and H1-antagonist (dimedrol) was revealed in ABA patients. The same phenomenon
      was registered at the preclinical stage of BA. In ABA and in preclinical BA the
      shift of H1/H2-histaminergic balance to increased H1-activity exists. Peroxide
      and hyperosmolar effects modeled on red cell membranes allowed us to characterize
      reactivity of adrenergic and histaminergic systems not only in ABA but also in
      preclinical BA.

PMID- 14971158
TI  - [Clinical and immunologic correlations of gastroduodenal lesions in patients with
      bronchial asthma].
AB  - To study local immunity of the stomach in bronchial asthma (BA) and the role of
      some immunity factors deficiency in development of gastroduodenal disturbances in
      BA patients, we have examined 271 male and female patients aged 18 to 60 years
      with exogenic and mixed BA of different severity. Gastroduodenal erosions were
      endoscopically diagnosed in 61 (22.5%) patients. We discovered that
      gastroduodenal pathology in BA develops in local deficiency of secretory IgA
      (sIgA) and high content of IgG and CIC in the gastric mucus. We registered a dose
      dependent effect of long-term oral therapy with systemic glucocorticoids (SGC) in
      BA on gastroduodenal pathology and local immunity. Physiological doses reduce
      concentrations of IgG and CIC in gastric mucus and, by attenuation of
      immunocomplex reactions in gastric mucosa, decreased the rate of gastroduodenal
      erosions. Treatment with supraphysiological doses of SGC breaks specific defense
      of gastric mucosa and makes erosions more frequent. Thus, the above derangement
      of humoral immunity of the stomach in patients with non-hormone-dependent BA has
      common manifestations and direction with local immunity of the respiratory
      airways in BA suggesting involvement of "common immune system of the mucosas" in
      BA.

PMID- 14971159
TI  - [Short-chain fatty acids and implications of their measurement in the diagnosis
      of encephalopathies].
AB  - Sixty patients with chronic hepatitis of various etiology at the stage of hepatic
      cirrhosis with hepatic encephalopathy syndrome (HES), thirty patients with
      cerebral atherosclerosis with dyscirculatory encephalopathy (DE) and 60 healthy
      controls have been examined in the study of basic diagnostic criteria of
      encephalopathies by short-chain fatty acids (SCFA) serum levels. Sensitivity and
      specificity of this test was also evaluated. Gas-liquid chromatography determined
      SCFA in the feces and peripheral blood serum from the above examinees. It was
      found that relative consent of SCFA and for the most part profiles of propionic
      and fat acids, acids with long chains, SCFA isomers in patients with
      encephalopathy of different genesis correlate with the results of clinical,
      laboratory and psychometric methods of examination and should be used together.
      Basic criteria are devised.

PMID- 14971160
TI  - [Statin therapy is a basic treatment for coronary heart disease].
AB  - The information is reviewed on significant effectiveness of statins in different
      forms of coronary heart disease in the range from angina pectoris to acute
      myocardial infarction. Positive treatment results were achieved both in high and
      normal hemoglobin.

PMID- 14971161
TI  - [Effectiveness of ketonal and diclofenac in spondylarthrosis complicated with
      spinal pain].
AB  - The article compares efficacy and safety of ketonal used in a dose 300 mg/day and
      diclofenac in a dose 150 mg/day in patients with primary spinal pain. The
      treatment of 60 patients aged 35 to 70 years (mean age 42.7 +/- 12.4 years)
      showed high efficacy of ketonal in spinal pain and low rate of side effects
      induced by this drug. Diclofenac was also effective.

PMID- 14971162
TI  - [Differential diagnosis in jaundice].

PMID- 14971163
TI  - [Tuberculosis in HIV-infected and AIDS patients].
AB  - The course of the combined infection (tuberculosis plus HIV-infection) has been
      analysed in 41 patients. Of them, 24 patients developed tuberculosis in the
      presence of HIV-infection (group 1) and 17 were infected with HIV when they
      already had tuberculosis running up to 5 years. HIV-infection in group 1 ran a
      more severe course, the patients developed generalized, disseminated and
      complicated forms of tuberculosis with more frequent lethal outcome. 39 patients
      of both groups received specific antituberculous therapy including 1-5 drugs. A
      response to treatment was achieved in 23 (60%) patients (52 and 47.8% at early
      and late HIV-infection stages, respectively). Treatment failure was explained by
      development of severe opportunistic infections and secondary diseases
      (generalized cytomegalovirus infection, advanced candidiasis, toxoplasmosis),
      poor compliance, asocial life style, advanced tuberculosis process, late
      diagnosis, inadequate treatment. It is shown that in late HIV-infection positive
      results of treatment can be expected only in early detection of tuberculosis and
      active long-term treatment.

PMID- 14971164
TI  - Geographic trends in cervical cancer incidence and mortality in Kentucky, 1995
      2000.
AB  - BACKGROUND: Kentucky's elevated cervical cancer incidence and mortality rates are
      well documented. However, in Kentucky, as in the United States as a whole,
      cervical cancer incidence and mortality have been decreasing. METHODS: To
      determine if the incidence and mortality declines in Kentucky are similar in
      different geographic regions of the state, incidence and mortality data for the
      six-year period 1995-2000 were analyzed by five geographic subdivisions. RESULTS:
      Overall, both incidence and mortality rates declined during the six-year period;
      however, there were variations in the decline by geographic subdivisions. In 1995
      2000, the greatest percentage decrease (43%) in incidence rates among the
      geographic subdivisions occurred in Fayette/Jefferson counties while their
      mortality rates increased (12%). Conversely, the Appalachian region of the state
      had a lower percentage decrease (11%) in incidence with a concurrent percentage
      decrease in mortality (45%). CONCLUSIONS: Intensified screening efforts may have
      resulted in increased detection of early stage cervical disease; which provided a
      subsequent reduction in mortality for the Appalachian region of the state, while
      Fayette/Jefferson County has a mortality rate that slopes upward necessitating
      additional investigation.

PMID- 14971165
TI  - Is the Kentucky prescription reporting system useful in the care of hospitalized
      patients?
AB  - Patients who are physically dependent on prescription drugs often create clinical
      management problems during hospitalization. Identifying those patients who have
      prescription drug problems can be difficult at the time of admission, but the
      information of the Kentucky All Schedule Prescription Electronic Reporting
      (KASPER) system can be useful clinically. The purpose of this study was to
      examine the value of the KASPER system in the management of patients admitted to
      an acute care hospital. A convenience sample of 58 hospitalized patients was
      evaluated. The patients' clinical and demographic data were abstracted from the
      medical record. The KASPER data were used to confirm the patients' history of
      drug use. In this sample, the KASPER data supplied additional, clinically useful
      information that was not available from the clinical history or screening
      toxicology from 30 (51.7%) of these patients. We conclude that the KASPER system
      has the potential to assist physicians in the care of hospitalized patients who
      take controlled drugs that are obtained by physician prescription and filled in
      Kentucky pharmacies.

PMID- 14971166
TI  - Are our children overexposed?

PMID- 14971167
TI  - Are you hiring terrorists?

PMID- 14971168
TI  - One-stop shopping. Comprehensive resources make Safety.BLR.com a good tool for
      OSH professionals.

PMID- 14971169
TI  - Unnatural accumulation of ice: an engineer's perspective.

PMID- 14971170
TI  - Advanced safety mat guarding.

PMID- 14971171
TI  - Seed-based metalworking fluid.

PMID- 14971172
TI  - Strategies for preventing manual handling injury.

PMID- 14971173
TI  - Two-fisted mousing: not just a macho thing!

PMID- 14971174
TI  - Respirators for emergency escape.

PMID- 14971175
TI  - Defusing the explosive worker.

PMID- 14971176
TI  - Safety incentives: myths and realities.

PMID- 14971177
TI  - The three Cs....

PMID- 14971178
TI  - Positive strokes lead to safer folks.

PMID- 14971179
TI  - Eight steps to selecting health & safety software.
AB  - Selecting the appropriate software, one that meets your requirements and budget,
      is a big project. If done properly, the entire process should only take a few
      months, depending on the complexity and size of your project. Establish a
      detailed project plan and assign tasks, responsibilities, and deadlines. Of most
      importance, monitor your progress and adjust accordingly.

PMID- 14971180
TI  - Keep these glove selection issues in mind.

PMID- 14971181
TI  - Creative solutions.

PMID- 14971182
TI  - Curbing OSHA's egregious penalty policy.

PMID- 14971183
TI  - Consumption of water in care homes.

PMID- 14971184
TI  - The Old World, positive future. Interview by Jacob Lonsdale.

PMID- 14971185
TI  - International perspectives: the influence of gender on lifetime physical activity
      participation.

PMID- 14971186
TI  - Genetics, physical activity, fitness and health: what does the future hold?

PMID- 14971187
TI  - Getting the inactive active: implications for public health policy [corrected].

PMID- 14971188
TI  - The experiences of older people participating in exercise referral schemes.
AB  - Exercise referral schemes (ERS) have become a major routeway of promoting
      physical activity with older adults. However, there is lack of evidence regarding
      the views of older people and their experience from participating in ERS. The
      purpose of this study was to offer insights into how physical activity (PA) is
      situated in notions of successful ageing of people participating in ERS and to
      highlight points for achieving client-based targets through ERS. Thirteen
      community-living, retired, older adults (five females) with ages ranging from 63
      to 79 who were at various stages in their referral programme were selected from
      three exercise referral schemes in south west England. The respondents chose to
      participate in either an individual or a group semi-structured interview.
      Findings stress that ERS clearly disrupt a lifestyle characterised by growing
      purposelessness and social isolation, offer older participants better physical
      and mental function and feelings of accomplishment and success. The participants
      in this study made a range of personally valued improvements through their
      involvement in ERS. The success of the programmes relies on the general
      practitioners' recommendations, the professional help and support from
      enthusiastic and experienced personnel and the attractiveness of the exercise
      content which needs to satisfy the multiple needs of the well-being of older
      adults.

PMID- 14971189
TI  - Accumulating aerobic exercise for effective weight control.
AB  - PURPOSE: To compare the effects of different patterns of regular treadmill
      walking and cycle ergometry on body weight, body composition, waist and hip
      circumferences in overweight adult Singaporean females. METHODS: Thirty
      overweight (BMI > 23 kg/m2) Singaporean females, aged 42.2 +/- 5.4 yr (mean +/-
      SD), all spasmodically physically active, were randomly assigned to two different
      eight-week programmes of aerobic exercise. One programme involved walking and
      cycling on indoor exercise machines at a moderate, comfortable intensity until
      400 kcals had been expended, five times a week, thus giving a total weekly energy
      expenditure of 2,000 kcal. The other programme involved the same type of exercise
      but expending 1,000 kcal per session on two days a week, thereby giving the same
      weekly energy expenditure. Body weight, body mass index, body composition, waist
      and hip circumferences were measured before and after each programme. Prior to
      commencement of the study all subjects attended a one hour seminar on nutrition,
      health and fitness where the project structure was explained. They were asked not
      to change their eating habits during the intervention period and food diaries
      were kept and monitored weekly. RESULTS: All subjects completed the eight-week
      programmes of exercise. Both programmes significantly reduced body weight, body
      mass index, percentage body fat and waist circumference (all p < 0.05). These
      reductions were identical in both the short-bout and long-bout programmes. No
      changes were observed in either group for hip circumference or lean body mass.
      CONCLUSION: These findings demonstrated the effectiveness of moderate aerobic
      exercise in reducing body weight, body fat percentage and waist circumference
      whilst maintaining lean body mass in moderately overweight Singaporean females.
      The study also demonstrated that whether the exercise is performed in a series of
      short bouts five times a week or in longer bouts twice a week, the results are
      identical, providing that the total weekly energy expenditure remains the same.

PMID- 14971190
TI  - Physical activity and sedentary behaviours in youth: issues and controversies.
AB  - There is growing concern over the effects of sedentary lifestyles on the health
      of young people. Recent rapid increases in juvenile obesity have received a great
      deal of attention in the scientific and popular press and have been attributed
      partly to television viewing, computer games and other sedentary behaviours.
      These are thought to compete with physical activity. There is a 'moral panic'
      concerning the 'couch kids' culture in modern western society. Project STIL
      (Sedentary Teenagers and Inactive Lifestyles) at Loughborough University is
      investigating 'what young people do' and focuses on active and inactive pursuits
      chosen in their leisure time. The following issues are addressed in this paper
      with specific reference to young people: how do we define 'sedentary behaviour'
      and do key sedentary behaviours displace physical activity? Are key sedentary
      behaviours obesogenic? What are the secular trends for children and youth for TV
      viewing? Our results for young people suggest that: 1. TV viewing and video-game
      playing are largely uncorrelated with physical activity, suggesting that there is
      time for both 2. meta-analytic findings show that body fatness is not related in
      any clinically meaningful way with key sedentary behaviours 3. although more
      children and youth have greater access to TVs than in previous generations, the
      amount of TV watched per head has not changed for 40 years. Preliminary findings
      from Project STIL suggest that inactivity is more complex that we sometimes
      think. Indeed, measures of 'couch potato-ism', such as TV viewing, may be
      inappropriate markers of inactivity.

PMID- 14971191
TI  - Childhood obesity and the role of physical activity.
AB  - Similar to adult obesity, childhood obesity has recently become a serious threat
      to public health. Children face the same environmental and lifestyle challenges
      that have made high energy dense food and drink increasingly available and
      opportunities for energy expenditure through transport and active play less
      likely. Governments are becoming concerned but research has been under funded, is
      relatively scarce in the UK and has provided little sound evidence on which to
      base interventions. Physical activity seems to be declining and there is some
      evidence that time spent in sedentary pursuits such as TV watching is increasing
      and that this may be related to obesity. However, not all children are inactive
      and it may be more fruitful to independently examine different elements of
      activity such as play, walking and cycling as transport, organised sports, and
      active jobs so that children's profiles of activity can be mapped on an
      individual and group level. Recent research using accelerometry is providing
      insight into those elements which produce significant energy expenditure in a
      child's daily routine. The school and the structure to the school day appear
      particularly important. It is also likely that attention will need to be paid to
      parenting--the anxieties that parents demonstrate when making decisions about the
      freedom of their child to be active. Furthermore, without neighbourhoods that are
      safe and attractive for activity it is unlikely that levels will be increased.
      For physical activity to contribute to reversing the trend in childhood obesity,
      a multi-factorial and multi-agency solution will be required that involves
      schools, the home, the neighbourhood and considered local planning and provision.

PMID- 14971192
TI  - Some puzzling situations in the onset, occurrence and future of coronary heart
      disease in developed and developing populations, particularly such in sub-Saharan
      Africa.
AB  - Coronary heart disease (CHD) was rare in developed populations until the early
      1900s; this prevailed even among the small segments who were prosperous and who,
      in measure, had most of the currently recognised risk factors. However, in the
      1930s, with improved circumstances from general rises in socio-economic state,
      there were major increases in the occurrence and mortality rate from the disease,
      the latter reaching a third of the total mortality in some countries, as in the
      United Kingdom (UK). Puzzlingly, the inter-population diversity of the increases
      in CHD has been such that there are as much as five fold differences in CHD
      mortality rates, as, for example, between Poland and Spain. Within recent years,
      with appropriate treatments, the mortality rate has halved in some countries,
      again, as in the UK. However, the incidence rate of the disease has diminished
      little or hardly at all. Risk factors include a familial component and,
      nutritionally, over-eating, a high fat intake, relatively low intakes of plant
      foods, especially of vegetables and fruit and, non-nutritionally, smoking,
      excessive alcohol consumption and a low level of everyday physical activity. On
      the one hand, known risk factors, broadly, are considered to be capable of
      explaining only about half of the variation in the occurrence of the disease.
      Even at present, known risk factors far from fully explain the epidemiological
      differences in mortality rates. Yet, on the other hand, there is abundant
      evidence that in population groups, among whom risk factors are low or have been
      reduced, CHD incidence and mortality rates are lower. Notwithstanding this
      knowledge, broadly, there is very little interest in the general public in taking
      avoiding measures. As to the situation in developing populations, in sub-Saharan
      Africa, in urban Africans, as in Johannesburg, South Africa, despite considerable
      westernisation of life style and with rises in risk factors, CHD remains of very
      low occurrence, the situation thereby resembling, historically, its relatively
      slow emergence in developed populations. In most eastern countries, mortality
      rates remain relatively low, as in Russia and Japan. However, in major contrast,
      in India, rates have risen considerably in urban dwellers. Indeed, in Indian
      immigrants, as in those in the UK, their rate actually exceeds that in the
      country's white population. In brief, much remains to be explained in the
      epidemiology of the disease.

PMID- 14971193
TI  - [The influence of botulinum toxin type A on vasomotor rhinitis and morphological
      study].
AB  - OBJECTIVE: To investigate the effect and mechanisms of botulinum toxin type
      A(BTA) on vasomotor rhinitis. METHOD: A retrospective study of 32 patients with
      vasomotor rhinitis who received BTA injection at 4 points in bilateral nasal
      cavities with 2.5 units at each point had been done. The state of rhinorrhea,
      nasal obstruction, sneeze and nasal mucosa edema of each patient were recorded
      and scored before and after the application of BTA respectively with follow-ups
      of 6-30 months. Twelve guinea pigs were randomly divided into 2 groups: BTA group
      and control group. Merocel sponge soaked with 10 units (0.2 ml) BTA was put into
      left nasal cavity under general anesthesia for one hour in BTA group. Saline
      replaced BTA in control group. The inferior turbinate mucosa of guinea pig ware
      harvested under general anesthesia at 7, 14, 28 days after BTA treatment and was
      observed with HE staining and electron microscope. RESULT: Rhinorrhea improved
      significantly in all 32 patients while sneeze, nasal obstruction and mucosa edema
      reduced partly. The reducing of rhinorrhea lasted averagely 6 weeks. Twelve
      patients had an episode of nasal dryness or increased rhinorrhea at the day of
      injection. No other complications were found. Seven, fourteen days after local
      BTA application, the degenerations of glandular epithelium and canal epithelium
      were observed in nasal mucosa of guinea pigs. Most of the glandular cells showed
      normal at 28 days after BTA treatment. CONCLUSION: BTA can induce the
      degeneration of glandular cells in nasal mucosa and thus obviously relieve over
      rhinorrhea of patients with vasomotor rhinitis.

PMID- 14971194
TI  - [Comparison of the mucociliary transport rate of rhinitis sicca and atrophic
      rhinitis].
AB  - OBJECTIVE: To study the mucociliary transport function of rhinitis sicca and
      atrophic rhinitis, and to explore the standard of diagnosis. METHOD: The MTR of
      normal control group, the rhinitis sicca group and the atrophic rhinitis were
      determined by using saccharin, and then compared. Then MTR of rhinitis sicca
      treatment group were compared before and after treatment. RESULT: The MTR of
      normal group: (9.15 +/- 0.86) mm/min; the rhinitis sicca group: (5.84 +/- 0.48)
      mm/min and the atrophic rhinitis group: (3.36 +/- 0.07) mm/min. There were
      significant difference among them (P < 0.05). 25 patients of rhinitis sicca were
      treated by administering the pill of Gelomyrtol forte in 2 weeks. The MTR of
      rhinitis sicca were no significant difference before and after treatment (P >
      0.05). CONCLUSION: Rhinitis sicca is a separate nasal disease, which is different
      from atrophic rhinitis. It is important to find an effective treatment for the
      disease.

PMID- 14971195
TI  - [Migrating pharyngeal and cervical esophageal foreign bodies].
AB  - OBJECTIVE: A retrospective study of four patients at Singapore Tan Tock Seng
      Hospital was done to evaluate the presentation, investigation, and diagnosis of
      migrated forcing bodies. METHOD: Migration is said to have occurred in the
      presence of positive neck radiography and negative rigid esophagoscopy. Computed
      tomography is the investigation of choice to confirm migration and invaluable in
      localising the foreign body for exploration. RESULT: All the migrated foreign
      bodies were linear, sharp fish bones and had been removed successfully.
      CONCLUSION: Ingested foreign bodies which migrate extra-luminally are rare
      occurrences, and they may result in life threatening complications and should be
      treated.

PMID- 14971196
TI  - [Express of plasma ROS, SOD and GSH-PX in patients with nasopharyngeal
      carcinoma].
AB  - OBJECTIVE: To investigate the levels of plasma reactive oxygen species(ROS),
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in patients with
      nasopharyngeal carcinoma (NPC) and to observe the state of metabolism of free
      radical in patients with NPC and the effects of them on nasopharyngeal carcinoma.
      METHOD: The levels of plasma ROS, SOD and GSH-PX in 40 patients with NPC and 20
      normal controls were identified by Fenton reaction method, xanthine oxidase
      method and dithiocarbamate method respectively. RESULT: Plasma ROS
      activity[(11,327.835 +/- 483.777)/(U.ml-1)] in NPC increased significantly in
      comparison with the control group [(10,262.712 +/- 525.287)/(U.ml-1)] (P < 0.05).
      Plasma SOD and GSH-PX activities [(76.619 +/- 22.283)/(NU.ml-1), (98.653 +/-
      46.374)/AU] in NPC decreased significantly in comparison with the control group
      [(154.603 +/- 27.241)/(NU.ml-1), (307.872 +/- 116.275)/AU] (P < 0.05). But there
      was no significant difference of the levels of plasma ROS[(10,987.235 +/-
      469.340)/(U.ml-1), (10,081.53 +/- 488.409)/(U.ml-1), (12,085.044 +/-
      564.721)/(U.ml-1)], SOD[(79.517 +/- 20.368)/(NU.ml-1), (67.975 +/- 24.202)/(NU.ml
      1), (58.692 +/- 29.946)/(NU.ml-1)] and GSH-PX[(101.362 +/- 59.859)/AU, (89.338 +/
      42.259)/AU, (101.890 +/- 33.559)/AU] in different pathological kinds of NPC.
      CONCLUSION: The metabolism of free radical is disturbed and the ability of anti
      oxidation injury decreases significantly in patients with NPC, so anti-oxidation
      treatment should be given to suppress the development of NPC.

PMID- 14971197
TI  - [The clinical anatomy of lacrimal sac fossa].
AB  - OBJECTIVE: To explore the characteristic of lacrimal sac fossa on ESS and
      traditional maxillary operation, and to provide anatomy basis for the endoscopic
      endonasal dacryocystorhinostomy. METHOD: Twenty-three heads of adult cadaver
      specimens were examined including the shape, direction and the thickness of wall
      of lacrimal sac fossa. RESULT: The fossa is formed by the frontal portion of the
      maxillary bone and the lacrimal bone. The proportion of the frontal portion of
      the maxillary bone is bigger than the lacrimal bone. There is about 20 degrees
      between the rear wall of the fossa and the coronal plane. CONCLUSION: Before the
      endoscopic endonasal dacryocystorhinostomy we should scan the anterior portion of
      the medial orbital wall so that we can understand the anatomy of the fossa and
      improve the effect of the surgery.

PMID- 14971198
TI  - [Morphology of olfactory bulb, olfactory tract blood supply affected by
      anthrosclersis and its clinical significance].
AB  - OBJECTIVE: In order to provide morphological evidences for olfactory defect cased
      by olfactory bulb, olfactory tract ischemia, the origins, numbers, distributions
      and pathological changes about olfactory bulb, olfactory tract arteries were
      studied. METHOD: The distributions and pathological changes of olfactory bulb,
      olfactory tract arteries in 80 sides of adult brain specimens were observed with
      operation microscope, among which the nourishing arteries and nerve of olfactory
      tract in two sides aged from 60 to 70 were observed pathohistologically. RESULT:
      The blood supply of olfactory bulb, olfactory tract comes mainly form artery
      cerebral and posterior communicainy. 10% of these 60 sides arteries were of multi
      branch. 86.3% of them had atheroselerosis. 25.0% of the olfactory bulb and
      olfactory tract artery were blocked or narrow, and pathological changes in
      olfactory nerve such as atrophy were observed. CONCLUSION: Excluding other
      diseases, the olfactory defect in different degree of patients over 60 years old
      were caused possibly by atheroselerosis of the arteries at base of the brain.

PMID- 14971199
TI  - [Clinical analysis of selected transarterial embolization in treating
      uncontrolled epistaxis].
AB  - OBJECTIVE: To learn the effects and the correlative factors of selected
      transarterial embolization in treatment of uncontrolled epistaxis. METHOD: The
      abnormal ends of internal maxillary artery were selected embolized in 23 patient
      of uncontrolled epistaxis by digital subtraction angiography (DSA) of carotid,
      meanwhile the facial artery were also embolized in 5 patients. RESULT: It was
      confirmed that hypogenesis and malformation in the ends of internal maxillary
      artery were existed in all 23 cases during DSA. There was evidence of bleeding in
      15 patients, and facial artery with abnormal shape was found in 6 patients. Nose
      bleeding was stopped in 22 cases (95.6%) after embolized, including one had a
      recurrence of bleeding in 24 hours because of the foundation of new abnormal
      communications. The fail in one case might be related with taking out all the
      stuff in noses before embolization and/or bleeding facial artery. CONCLUSION:
      Uncontrolled epistaxis in this report might be caused by hypogenesis and
      malformation of internal maxillary artery. The effects of selected transarterial
      embolization were rapid and satisfactory. The fail in treatment might be related
      to foundation of new abnormal communications and bleed from facial artery. Taking
      out all the stuff in noses too early might also influence the effects of
      embolization.

PMID- 14971200
TI  - [Endoscopic treatment of nasopharyngeal angiofibroma].
AB  - OBJECTIVE: To evaluate the effect of endoscopic resection of nasopharyngeal
      angiofibroma. METHOD: Retrospective review was made of 7 patients with
      nasopharyngeal angiofibroma who were treated by endoscopic surgery from June 2001
      to January 2003. RESULT: All cases were successfully treated by endoscopic
      excision with no postoperative complication. The patients remained free of
      disease after follow-up period of 3-18 months. CONCLUSION: The endoscopic
      management of nasopharyngeal angiofibroma appears to be feasible techniques. The
      advantages includes the minimal bleeding, shorter duration and efficacy.

PMID- 14971201
TI  - [Selection of operative manner of inferior turbinate on hypertrophic rhinitis].
AB  - OBJECTIVE: To analyses the features of three operative manner of inferior
      turbinate on hypertrophic rhinitis (HR) and to propose some suggestion for
      selection of operative manner on HR. METHOD: One hundred and sixty-two cases of
      HR were treated separately by submucoperiosteous resection of inferior turbinate
      bone (group A), partial inferior turbinectomy (group B) and submucosal hot
      coagulation of inferior turbinate with microwave (group C). RESULT: Three groups
      of HR were followed up one year after operation, effective rate was 94.6% in
      group A, 83.7% in group B and 88.9% in group C respectively. Effective rate had
      no significant difference among three groups (P > 0.05). CONCLUSION:
      Submucoperiosteous resection of inferior turbinate bone is safe, effective manner
      for HR with inferior turbinate bony hypertrophy. The same is submucosal hot
      coagulation of inferior turbinate by microwave for mucosal hypertrophy. Partial
      inferior turbinectomy should be preformed cautiously on HR in order to protect
      the anatomical structure and physiologic functions of nose.

PMID- 14971202
TI  - [Radiofrequency ablation for treatment of nasal obstruction secondary to inferior
      turbinate hypertrophy].
AB  - OBJECTIVE: To assess the efficacy of bipolar radiofrequency ablation on inferior
      turbinate in patients with nasal obstruction caused by inferior turbinate
      hypertrophy. METHOD: Eighteen patients enrolled in the study and bipolar
      radiofrequency ablation was delivered to inferior turbinate. The preoperative and
      postoperative nasal obstruction were investigated by visual analogue scale (VAS).
      RESULT: All patients were improved in 3 months. Mean obstruction(VAS) improved
      from 70.5% +/- 10.5% to 53.3% +/- 11.6% (right side), and from 67.7% +/- 9.4% to
      45.0% +/- 9.2% (left side). CONCLUSION: The use of radiofrequency for submucosal
      tissue ablation in the hypertrophied inferior turbinate is an effective modality
      for reducing symptoms of nasal obstruction.

PMID- 14971203
TI  - [Study on the treatment of head and neck late recurrence tumors by using multi
      bullet radiofrequency therapy].
AB  - OBJECTIVE: To study the treatment to head and neck-late recurrence tumors by
      using multi-bullet radiofrequency therapy. METHOD: Eleven patients with late
      recurrence head and neck tumors were treated by using multi-bullet radiofrequency
      therapy. Before and after the therapy, the tumor size, pathologic alteration were
      assessed. The serial changes in tumor size after therapy were evaluated with CT
      imaging. The effects, side-effects and indications of this therapy were observed
      also. RESULT: The ablation, coagulation and necrosis of tumors were observed
      during the multi-bullet radiofrequency therapy in all this 11 patients. The
      tumors disappeared in CT scanning during 1.2-2.6 years follow up. CONCLUSION: Our
      study suggests that the multi-bullet radiofrequency therapy is a safe and
      effective treatment for patients with head and neck late recurrence tumors.

PMID- 14971204
TI  - [The study on plasma ET and NO of patients with sudden hearing loss].
AB  - OBJECTIVE: To study the significance of plasm NO and ET in sudden hearing loss.
      METHOD: We studied the plasma endothelin (ET) and NO in 32 cases of sudden
      hearing loss with radioimmunoassay (RIA) and nitrate reductase (NR) by using RIA
      and NR. RESULT: The content of plasma ET in sudden hearing loss group is higher
      than that in control group (P < 0.01), but the NO is lower (P < 0.01). The
      contents of plasma NO and ET between sudden hearing loss and treated sudden
      hearing loss group and that between the effective treatment group and effectless
      treatment group have significant differences (P < 0.01). CONCLUSION: The contents
      of plasma NO and ET will remarkably change during the process of sudden hearing
      loss and may accelerate the happening and development of the disease.

PMID- 14971205
TI  - [The injury of nasal mucosa in transnasal endoscopic sinus surgery by light and
      heat].
AB  - OBJECTIVE: To investigate the injury of nasal mucosa in transnasal endoscopic
      sinus surgery by light and heat. METHOD: The techniques of transmission electron
      microscope and scanning electron microscope were applied in order to observe the
      changes between normal and irradiation nasal septum mucosa of rabbits. RESULT: It
      showed that after irradiation, the cilia became mal-distributed, adhesive and
      exfoliative. With the elongation of irradiation, the spacing of the epithelium
      cells increased, the distribution of the cilia was sparse and the degree of their
      thickness was different, the mitochondria were highly bloated, accompanied with
      disappearance of the cristae and vacuolation of matrix, the nucleus of epithelium
      cells was edge-located, the distribution of the chromatin was mass, concentrated
      by the fringe, the nucleus was close to the cell surface and the exfoliation of
      goblet cells was visible. CONCLUSION: The light and heat in transnasal endoscopic
      sinus surgery can injure the nasal mucosa.

PMID- 14971206
TI  - [The effect on cilia movement of experimental maxillary sinusitis in rabbits with
      different propose to ostia and mucosa].
AB  - OBJECTIVE: To investigate the effect on cilia movement of experimental maxillary
      sinusitis in rabbits with different dispose to ostia and mucosa. METHOD: Forty
      New Zealand White rabbits which had been induced experimental sinusitis were
      divided into 3 groups according to mucosa dispose during operation. The another
      two groups were divided according to different dispose ostia of maxillary sinus.
      Activated charcoal powder was used to test mucociliary transport (MCT) of
      maxillary sinus. RESULT: All data had be processed statistically. MCT of rabbits
      before operation were faster than that after operation and both of them were
      faster than the sinusitis group(P < 0.01). The difference of MCT in different
      propose of ostia groups was not significant(P > 0.05). CONCLUSION: It's a
      effective method to estimate the function of cilia using activated charcoal
      powder to test MCT of maxillary sinus. The function of regenerate mucosa after
      operation is lower than normal mucosa. The difference of MCT between ostia
      enlarged operation and ostia patent surgery is not significant.

PMID- 14971207
TI  - [The orientation and its significance of aquaporin-2 in the rat inner ear].
AB  - OBJECTIVE: To study the distribution of aquaporin-2(water channel protein; Aqp-2)
      in various structures of the SD rat inner ear. METHOD: Fifteen SD rat were used
      in this experiment and were cardically perfused. The temporal bones were taken
      out, fixed in 4% paraformaldehyde, processed and sectioned by paraffin-embedded
      technique. The expression and distribution of Aqp-2 in the rat inner ear were
      examined by SP immunohistochemical technique. RESULT: Aqp-2 were observed mainly
      in endolymphatic sac, stria vascularis and spiral ganglion. In addition, Aqp-2
      were also labeled in Cortis organ, basilar membrane, vestibular lip and tympanic
      lip of spiral limus, tectorial membrane and spiral prominence. CONCLUSION: Aqp-2
      distributed in the rat inner ear tissues closely related with endolymph
      metabolism: the endolymphatic sac and stris vascularis. Its expression in the
      Corti's organ gave another explanation for the handicap hearing along with
      endolymphatic hydrops, and the distribution of Aqp-2 in the spiral ganglion
      indicated its possible role in the maintenance of hearing.

PMID- 14971208
TI  - [Mitochondrial DNA large deletions associated with presbycusis].
AB  - OBJECTIVE: By observing the relationship between the fragment deletion of
      mitochondrial DNA (mt DNA) of inner ear in rat and the hearing loss to
      investigate the possible role of mt DNA deletion in presbycusis. METHOD: Thirty
      wistar rats were divided into group A (young rat, 4 months, n = 15) and group B
      (old rat, 24-30 months, n = 15) according to the age. The threshold of the
      auditory brainstem response (ABR) was tested. The inner ear membranous labyrinth
      tissue was harvested and the mtDNA was amplified to identify 4,834 bp deletion by
      PCR technique. RESULT: The mean of ABR thresholds in group B (64.79 +/- 10.88 dB
      peSPL) was significantly higher than that in group A (40.00 +/- 4.66 dB peSPL) (P
      < 0.01). In group B, 9 of the 15 rats demonstrates the mtDNA 4,834 bp deletion,
      while no deletion was detected in group A. CONCLUSION: Deletion of mtDNA of inner
      ear tissue in old rat is found. The mtDNA deletion is associated with the
      presbycusis and may be one of the causes of presbycusis.

PMID- 14971209
TI  - Regulatory boredom.

PMID- 14971211
TI  - Regional anaesthesia in mountain rescue.

PMID- 14971212
TI  - Overproduction of food as the ultimate cause of obesity in the developed world.

PMID- 14971213
TI  - On being politically correct.

PMID- 14971214
TI  - No smoke without fire.

PMID- 14971215
TI  - A change of heart at Groote Schuur.

PMID- 14971216
TI  - Walter Sisulu Paediatric Cardiac Centre opened by Nelson Mandela.

PMID- 14971217
TI  - SAMA leads the way with ARV roll-out.

PMID- 14971218
TI  - G8 nations defaulting on promises to Global Fund.

PMID- 14971220
TI  - South Africa gains support from the Global Fund.

PMID- 14971219
TI  - UN says AIDS deaths at new high.

PMID- 14971221
TI  - The 3 by 5 initiative.

PMID- 14971222
TI  - Wits AIDS Research Institute awards over R2 million to HIV/AIDS research in SA.

PMID- 14971223
TI  - Approval for South African initiative to treat AIDS.

PMID- 14971224
TI  - Menopause and HRT--keeping perspective.

PMID- 14971225
TI  - Hormone replacement therapy--finally, good data.

PMID- 14971226
TI  - Annular pancreas.

PMID- 14971227
TI  - Medicine--is this what we practise?

PMID- 14971228
TI  - Measuring resistance to malaria.

PMID- 14971229
TI  - Residual house spraying against malaria must be done correctly to be effective.

PMID- 14971230
TI  - Chloroquine-induced retinal toxicity.

PMID- 14971231
TI  - Occupation and schizophrenia in a Xhosa population--a variant of the social drift
      theory?

PMID- 14971232
TI  - Safety and immunogenicity of two Haemophilus influenzae type b conjugate
      vaccines.
AB  - OBJECTIVES: Haemophilus influenzae type b (Hib) infection remains a major public
      health problem in the developing world. We evaluated the safety and
      immunogenicity of a new PRP-CRM197 conjugate Hib vaccine (Vaxem Hib, Chiron
      Vaccines), compared with the HibTITER vaccine (Wyeth-Lederle Vaccines), following
      the World Health Organisation (WHO)'s accelerated schedule which allows 4-week
      intervals between doses. STUDY DESIGN: A phase II, observer-blind, multicentre,
      randomised, controlled, non-inferiority study. METHODS: In total, 331 babies were
      immunised with either Vaxem Hib (N = 167) or HibTITER (N = 164) vaccine at 6, 10
      and 14 weeks of age, in parallel with oral polio, diphtheriatetanus-pertussis and
      hepatitis B vaccines. Post-immunisation reactions were recorded after each
      immunisation and at follow-up visits. Anti-polyribosylribitol phosphate (PRP)
      antibodies were measured using enzyme-linked immunosorbent assays (ELISAs) before
      and 1 month after the third immunisation. RESULTS: Overall, there was no
      significant difference in the anti-PRP levels between the two groups. One month
      after the third immunisation, 76% of vaccinees in the Vaxem Hib group and 70% in
      the HibTITER group had anti-PRP antibody titres > or = 1.0 microgram/ml, while
      96% of the Vaxem Hib group and 90% of the HibTITER group demonstrated anti-PRP
      antibody titres > or = 0.15 microgram/ml. The geometric mean titre at day 90 was
      3.77 micrograms/ml for the Vaxem Hib and 3.0 micrograms/ml for the HibTITER
      groups. Although the Vaxem Hib vaccine produced more redness (6% versus 1%; p =
      0.006) and swelling (5% versus 1%, p = 0.037), overall it was well tolerated
      compared with the HibTITER vaccine. There was no significant difference in
      vaccine-related elevated temperature (> or = 38 degrees C) between the two groups
      (p = 0.11). CONCLUSION: Both vaccines showed comparable safety and immunogenicity
      profiles when administered to South African babies at 6, 10 and 14 weeks of age.

PMID- 14971233
TI  - Susceptibility of Plasmodium falciparum to the drugs used to treat severe malaria
      (quinine) and to prevent malaria (mefloquine, cycloguanil) in Comoros Union and
      Madagascar.
AB  - OBJECTIVES: To monitor the sensitivity of Plasmodium falciparum to the drugs used
      to treat severe malaria and to prevent malaria in Comoros and Madagascar. DESIGN:
      We used the in vitro isotopic method to test the sensitivity of P. falciparum to
      quinine, mefloquine and cycloguanil. RESULTS: We tested fresh isolates of P.
      falciparum, collected from patients living in urban, suburban and rural areas and
      suffering from uncomplicated malaria in 2001, against at least one of the
      antimalarials cited above. In both countries all of the successfully tested
      isolates were sensitive to quinine (N = 243) and to cycloguanil (N = 67). The
      mean IC50 ranged from 85.7 to 133.7 nM for quinine. For cycloguanil, the mean
      IC50 ranged from 1.4 to 20.2 nM and the highest IC50 value (102.5 nM) was
      recorded in Comoros. Only 0.9% (1/110) of the informative isolates from
      Madagascar were mefloquine-resistant (0/18 in Comoros). The mefloquine mean IC50s
      were 8.2 nM, 14.1 nM and 11.6 nM respectively in the rural, suburban and urban
      areas of Madagascar, and 5.9 nM in Comoros. A positive correlation was found
      between quinine and mefloquine IC50s (N = 127, r = 0.48, p < 10(-6)), but in
      vitro mefloquine was 6-16 times more potent than quinine. No correlation was
      noticed between the activities of quinine and cycloguanil or between the
      activities of mefloquine and cycloguanil. CONCLUSION: We therefore advocate the
      use of a full-course regimen of quinine, as recommended by the World Health
      Organisation (WHO), to treat above all severe malaria in Madagascar and Comoros.
      Our results also demonstrate that the use of mefloquine- and cycloguanil-based
      antimalarials is still justified to prevent malaria in both countries, mainly in
      the case of travellers.

PMID- 14971234
TI  - Oral trimethoprim-sulfamethoxazole in the treatment of cerebral toxoplasmosis in
      AIDS patients--a prospective study.
AB  - Toxoplasma encephalitis is the commonest cause of intracranial mass lesions in
      AIDS patients. Effective therapy includes pyrimethamine plus sulfadiazine,
      clindamycin with pyrimethamine, and co-trimoxazole. This study examines the
      efficacy of oral co-trimoxazole in 20 AIDS patients with toxoplasmosis and seeks
      to confirm the experience of Torre et al.

PMID- 14971235
TI  - Islet neogenesis is stimulated by brief occlusion of the main pancreatic duct.
AB  - OBJECTIVE: Current models of islet neogenesis either cause substantial pancreatic
      damage or continuously stimulate the pancreas, making these models unsuitable for
      the study of early events that occur in the neogenic process. We aimed to develop
      a method where the initial events that culminate in increased pancreatic
      endocrine mass can be studied. DESIGN AND METHODS: Ten 12-week-old female Wistar
      rats were subjected to a midline laparotomy, the pancreas was isolated and the
      main pancreatic duct was occluded for 60 seconds. The pancreas was released and
      carefully relocated within the abdomen. Ten age-, strain- and sex-matched control
      rats were subjected to a sham operation. The animals were killed 56 days post
      occlusion, and the pancreata excised and fixed for histological analysis. Body,
      pancreatic and hepatic weights were noted at termination and serum was taken for
      analysis. The endocrine-to-exocrine ratio was calculated and the number of
      endocrine cells in each islet from the sectioned pancreata was counted. RESULTS:
      Occlusion of the main pancreatic duct for 60 seconds results in an increase in
      endocrine mass by 80% 56 days post occlusion. This constitutes an increase in
      endocrine units (1-6 cells), and in small (7-30 cells), medium (31-60 cells) and
      large (> 60 cells) islets by 85%, 96%, 95% and 71% respectively. CONCLUSION:
      Brief occlusion of the main pancreatic duct results in an increase in pancreatic
      endocrine mass. An increase in endocrine units and small islets is indicative of
      islet neogenesis. Therefore, owing to the briefness of the stimulation, this
      model can therefore be used to study the initial events that occur during the
      neogenic process.

PMID- 14971236
TI  - Homicidal violence during foreign military missions--prevention and legal issues.
AB  - OBJECTIVES: The study involved Nigerian soldiers engaged in peacekeeping missions
      in Liberia and Yugoslavia. Using case illustrations, the study sought to describe
      patterns of homicidal violence among soldiers from the same country or soldiers
      from allied forces, and to suggest possible reasons for the attacks. DESIGN AND
      SETTING: Nigeria was actively involved in peacekeeping missions in Liberia
      between 1990 and 1996. During this period, intentional homicidal attacks occurred
      among the Nigerian military personnel. Post-homicidal interviews conducted among
      the perpetrators were combined with evidence obtained at military courts to
      produce the case studies. SUBJECTS: Six Nigerian military personnel who attacked
      other Nigerians or soldiers from allied forces, with homicidal intent. RESULTS:
      Possible predisposing and precipitating factors for these attacks were
      highlighted. The possibility of recognising these factors before embarking on
      overseas missions was discussed, so that preventive measures could be instituted
      as far as possible. Finally, medico-legal implications of homicide in the
      military were discussed. CONCLUSIONS: A certain degree of pre-combat selection is
      essential to exclude soldiers with definite severe psychopathology. A clearly
      defined length of duty in the mission areas and adequate communication with home
      could reduce maladjustment. Health personnel deployed to mission areas should be
      very conversant with mental health issues so that early recognition of
      psychological maladjustment is possible.

PMID- 14971237
TI  - The shape of things to come.

PMID- 14971238
TI  - Up the agenda.

PMID- 14971239
TI  - Delayed discharge.

PMID- 14971240
TI  - The hsj intervew: Margaret Hodge. The young at heart. Interview by Nick Edwards.

PMID- 14971241
TI  - Clinical management. Where medicine meets management. Crib notes.
AB  - This is a year of change for children's services, with reports, proposals and new
      clinical guidelines. Some primary care trusts have been accused of using the
      focus on the core programme as a way of cutting services. A royal college report
      may clash with the imminent national service framework.

PMID- 14971242
TI  - Organisational theory. Find the on switch.

PMID- 14971243
TI  - Finance. Choice catches.

PMID- 14971244
TI  - HSJ people. Off the scale.

PMID- 14971245
TI  - The use of the evidence-based approach in a periodontal therapy contemporary
      science workshop.
AB  - BACKGROUND: When appropriately evaluated and carefully managed, the integration
      of emerging technology into practice can improve health and enhance the quality
      of life. Since the last American Academy of Periodontology Workshop in 1996,
      great technological advances in the areas of data access, retrieval, and
      management have been made. The World Wide Web has "exploded" with great
      possibilities for gathering data from many sources. Evaluation methods such as
      meta-analysis and modeling have likewise improved, permitting a more objective
      and useful assessment of the retrieved information. The purpose of this paper is
      to demonstrate how the evidence-based (EB) approach was used to plan and
      implement a consensus conference on periodontal therapy, the Workshop on
      Contemporary Science in Clinical Periodontics. RATIONALE: The methodologies and
      philosophies associated with the EB approach provided the ideal framework for
      assessing the applicability of the newest clinical research to patient therapy.
      METHODS: Evidence-based systematic reviews on 15 topics associated with
      contemporary clinical periodontal practice were conducted prior to the Workshop.
      High standards of scientific rigor and scholarly ideals were stressed throughout
      the process. At the highly structured conference the reviews served as the basis
      for development of consensus reports that include implications for practice and
      research. MATERIAL COVERED: 1. The rationale, design, and implementation of a
      conference on contemporary clinical periodontics using an evidence-based
      approach. 2. Data management, clinical versus statistical significance, and the
      challenges of technology transfer and dissemination. 3. The benefits and
      limitations of using the EB approach in a consensus conference. CONCLUSIONS: The
      consensus statements resulting from the conference should serve to augment
      clinical decision-making, research priorities, education, and reimbursement. The
      evidence-based approach removed much of the subjectivity traditionally associated
      with classical reviews of the literature and allowed participants to focus on
      substantive issues.

PMID- 14971246
TI  - Periodontal host modulation with antiproteinase, anti-inflammatory, and bone
      sparing agents. A systematic review.
AB  - BACKGROUND: The use of modulating agents, including inhibition of matrix
      metalloproteinases (MMPs) with antiproteinases, blocking production of
      proinflammatory cytokines and prostaglandins with anti-inflammatory drugs, and
      inhibiting activation of osteoclasts with bone-sparing agents, has been
      postulated to be of therapeutic value as an adjunctive therapy to the management
      of chronic periodontitis. RATIONALE: The objective of this systematic review of
      the literature was to assess the adjunctive efficacy of antiproteinase, anti
      inflammatory, and bone-sparing host-modulating agents in the treatment of
      gingivitis, aggressive periodontitis, and chronic periodontitis. FOCUSED
      QUESTIONS: 1. In patients with periodontal diseases, what is the effect of host
      modulation agents, alone or combined with conventional therapy, compared to
      conventional therapy alone as assessed by clinical, radiographic, adverse, and
      patient-centered outcomes? 2. In patients with dental implants, what is the
      effect of host-modulation agents on implant success assessed by clinical,
      radiographic, adverse, and patient-centered outcomes? SEARCH PROTOCOL: MEDLINE,
      Embase, and the Cochrane Library databases were searched without language
      restrictions through April 1, 2002 for studies that used tetracycline (TET)
      related matrix metalloproteinase (MMP) inhibitors, or non-steroidal anti
      inflammatory drugs (NSAIDs) and bisphosphonate anti-osteolytic agents. The
      investigation also included hand searching of journals and contacting authors and
      industry experts. SELECTION CRITERIA:  INCLUSION CRITERIA: Only human studies
      (randomized controlled clinical trials, cohort studies, case-control studies,
      cross-sectional studies, and case series) were selected. Studies were on subjects
      with gingivitis, aggressive or chronic periodontitis, or dental implants.
      Interventions included TET-related MMP inhibitors, NSAIDs, or bisphosphonate anti
      osteolytic agents. EXCLUSION CRITERIA: Studies that used MMP tissue inhibitors as
      diagnostic or prognostic indicators of periodontal disease or that evaluated
      short-term systemic antibodies or locally delivered levels of drugs with
      antiproteinase activity were excluded. DATA COLLECTION AND ANALYSIS: The primary
      outcomes for assessment were changes in bone or clinical attachment levels (CAL);
      secondary outcomes included clinical measures of plaque, gingival inflammation,
      probing depth (PD), and mobility. Summary data appropriate for meta-analysis were
      pooled using a weighted average and analyzed using a standardized difference; the
      results were checked with both fixed-effects and random-effects models. MAIN
      RESULTS: 1. A meta-analysis done on the studies reporting changes in CAL and PD
      following administration of sub-antimicrobial doses of doxycycline (SDD) in
      conjunction with scaling and root planing (SRP) in patients with periodontitis
      showed a statistically significant beneficial adjunctive effect. 2. There were
      insufficient data to provide meta-analyses on periodontal patients treated with
      other host-modulating agents; descriptive tables are included. 3. NSAIDS show
      promise in their ability to slow periodontal disease. 4. Preliminary data on
      bisphosphonate agents indicate there is a potential role for these agents in
      periodontitis management. 5. There are a very limited number of studies on host
      modulating agents and dental implants and no analyses were possible. 6. Because
      the treatment methodologies and clinical variables differed considerably among
      the studies, it is difficult to summarize the information and identify a reliable
      total patient population. REVIEWERS' CONCLUSIONS: 1. Large multi-center trials
      are needed to evaluate the role of host-modulating agents in the treatment of
      periodontitis. 2. NSAIDS and bisphosphonate drugs may have a potential adjunctive
      role in periodontal therapy. 3. The adjunctive use of SDD with SRP is
      statistically more effective than SRP alone in reducing PD and in achieving CAL
      gain.

PMID- 14971247
TI  - Associations between periodontal disease and risk for atherosclerosis,
      cardiovascular disease, and stroke. A systematic review.
AB  - BACKGROUND: Recent studies implicate exposure to systemic conditions involving
      chronic inflammation, including chronic periodontitis, in the etiology of
      atherosclerosis. RATIONALE: A systematic review of the literature was conducted
      to assess the association between chronic inflammatory periodontal disease and
      atherosclerosis. FOCUSED QUESTION: Does periodontal disease influence the
      initiation/progression of atherosclerosis and, therefore, cardiovascular disease
      (CVD), stroke, and peripheral vascular disease (PVD)? SEARCH PROTOCOL: MEDLINE,
      pre-MEDLINE, MEDLINE Daily Update, and the Cochrane Controlled Trials Register
      were searched to identify human studies that related variables associated with
      atherosclerosis to periodontal disease. Searches were made for papers published
      from 1966 through March 2002. INCLUSION CRITERIA: Published randomized controlled
      clinical trials (RCTs), longitudinal, cohort, and case-control studies were
      included. Study participants included those with atherosclerosis, myocardial
      infarction (MI), stroke, or PVD. Oral conditions included periodontal disease.
      EXCLUSION CRITERIA: Only studies on humans were included. DATA COLLECTION AND
      ANALYSIS: Because the studies used different oral assessment measures, it was not
      possible to perform a meta-analysis of the data reported. Weighted mean
      differences, relative risks, or odds ratios were compared for cohort studies.
      MAIN RESULTS: 1. Of the initial 1,526 studies identified, 31 (including 8 case
      control and 18 cross-sectional reports) were included in the analysis. Taken
      together, most of the literature supports a modest association between
      periodontal disease and atherosclerosis. However, data reported in several
      studies do not show this association. 2. The absence of a standard definition and
      measures for periodontal disease complicates interpretation of results, as do
      potential confounding risk factors common to both conditions. REVIEWERS'
      CONCLUSIONS: 1. Periodontal disease may be modestly associated with
      atherosclerosis, MI, and CVD. 2. Additional large-scale longitudinal
      epidemiologic and intervention studies are necessary to validate this association
      and to determine causality.

PMID- 14971248
TI  - Associations between periodontal disease and risk for nosocomial bacterial
      pneumonia and chronic obstructive pulmonary disease. A systematic review.
AB  - BACKGROUND: Several recent studies provide evidence that the oral cavity may
      influence the initiation and/or the progression of lung diseases such as
      pneumonia and chronic obstructive pulmonary disease (COPD). RATIONALE: Studies
      have shown that poor oral hygiene and periodontal disease may foster colonization
      of the oropharyngeal region by respiratory pathogens, particularly in hospital or
      nursing home patients. If aspirated, these pathogens can cause pneumonia, one of
      the most common respiratory infections, especially in institutionalized subjects.
      Other cross-sectional epidemiologic studies point to an association between
      periodontal disease and COPD. This systematic review examines the literature to
      determine if interventions that improve oral hygiene reduce the rate of pneumonia
      in high-risk populations. FOCUSED QUESTION: Do periodontal diseases or other
      indicators of poor oral health influence the initiation/progression of pneumonia
      or other lung diseases? SEARCH PROTOCOL: MEDLINE, pre-MEDLINE, MEDLINE Daily
      Update, and the Cochrane Controlled Trials Register were searched to identify
      published studies that related variables associated with pneumonia and other lung
      disease to periodontal disease. Searches were performed for articles published in
      English from 1966 through March 2002. INCLUSION CRITERIA: Randomized controlled
      clinical trials (RCTs), longitudinal, cohort, and case-control studies were
      included. Study populations included patients with any form of pneumonia or
      chronic obstructive pulmonary disease (COPD) and periodontal disease, as measured
      by assessments of gingival inflammation, probing depth, clinical attachment
      level, and/or radiographic bone loss, or oral hygiene indices. EXCLUSION
      CRITERIA: Limited to studies of humans. DATA COLLECTION AND ANALYSIS: The summary
      statistics used to analyze the RCTs included weighted mean differences in rates
      of disease between control and intervention groups. For cohort studies that
      measured differences in rates of disease between groups with and without oral
      disease, weighted mean differences, relative risks, or odds ratios were compared.
      A meta-analysis was performed on the 5 intervention studies to determine the
      relationship between oral hygiene intervention and rate of pneumonia in
      institutionalized patients. MAIN RESULTS: Of the initial 1,688 studies
      identified, 36 satisfied all inclusion criteria and were read. Of these, 21 (11
      case-control and cohort studies [study population 1,413] and 9 RCTs [study
      population 1,759]) were included in the analysis. 1. A variety of oral
      interventions improving oral hygiene through mechanical and/or topical chemical
      disinfection or antibiotics reduced the incidence of nosocomial pneumonia by an
      average of 40%. 2. Several studies demonstrated a potential association between
      periodontal disease and COPD. REVIEWERS' CONCLUSIONS: 1. Oral colonization by
      respiratory pathogens, fostered by poor oral hygiene and periodontal diseases,
      appears to be associated with nosocomial pneumonia. 2. Additional large-scale
      RCTs are warranted to provide the medical community with further evidence to
      institute effective oral hygiene procedures in high-risk patients to prevent
      nosocomial pneumonia. 3. The results associating periodontal disease and COPD are
      preliminary and large-scale longitudinal and epidemiologic and RCTs are needed.

PMID- 14971249
TI  - Periodontal disease as a risk factor for adverse pregnancy outcomes. A systematic
      review.
AB  - BACKGROUND: Recent studies have implicated a variety of infections, including
      periodontal diseases, as risk factors for adverse pregnancy outcomes such as
      prematurity and low birth weight. RATIONALE: A number of studies have shown that
      bacterial vaginosis is related to preterm and/or low birth weight (PT/LBW), which
      continues to be a significant cause of infant morbidity and mortality. It is also
      possible that other infectious processes, including periodontal diseases,
      contribute to PT/LBW. This systematic review examines the literature to determine
      the possible relationship between PT/LBW and periodontal diseases. FOCUSED
      QUESTION: Does prevention/control of periodontal disease as compared to controls
      have an impact on the initiation/progression of adverse pregnancy outcomes?
      SEARCH PROTOCOL: MEDLINE, pre-MEDLINE, MEDLINE Daily Update, and the Cochrane
      Oral Controlled Trials Register were searched to identify published studies that
      related variables associated with PT/LBW and periodontal disease. Searches were
      performed for articles published through October 2002. INCLUSION CRITERIA:
      Randomized controlled clinical trials (RCTs), case-control, and cohort studies
      were included. Study populations included mothers, with or without periodontal
      disease, who gave birth to preterm and/or mature infants. The interventions
      considered included all forms of periodontal therapy. EXCLUSION CRITERIA: Only
      studies on humans were included. DATA COLLECTION AND ANALYSIS: Due to study
      heterogeneity, meta-analysis was not possible. MAIN RESULTS: 1. Of the over 660
      studies identified, 12 (6 case-control, 3 cross-sectional and longitudinal, and 3
      intervention) met inclusion and exclusion criteria and were included in the
      analysis. 2. While several studies implicated periodontal disease as a risk
      factor for PT/LBW, few assessed the impact of the prevention and treatment of
      periodontal disease on outcomes. 3. Several epidemiologic studies did not support
      periodontal disease as a risk factor for PT/LBW. REVIEWERS' CONCLUSIONS: 1.
      Periodontal disease may be a risk factor for PT/LBW. 2. Additional longitudinal,
      epidemiologic, and interventional studies are needed to validate this association
      and to determine whether it is causal. 3. It is not yet clear whether periodontal
      diseases play a causal role in adverse pregnancy outcomes. 4. Preliminary
      evidence to date suggests that periodontal intervention may reduce adverse
      pregnancy outcomes.

PMID- 14971250
TI  - Local anti-infective therapy: pharmacological agents. A systematic review.
AB  - BACKGROUND: It is well recognized that periodontal diseases are bacterial in
      nature. An essential component of therapy is to eliminate or control these
      pathogens. This has been traditionally accomplished through mechanical means
      (scaling and root planing [SRP]), which is time-consuming, difficult, and
      sometimes ineffective. Over the past 20 years, locally delivered, anti-infective
      pharmacological agents, most recently employing sustained-release vehicles, have
      been introduced to achieve this goal. RATIONALE: This systematic review evaluates
      literature-based evidence in an effort to determine the efficacy of currently
      available anti-infective agents, with and without concurrent SRP, in controlling
      chronic periodontitis. FOCUSED QUESTION: In patients with chronic periodontitis,
      what is the effect of local controlled-release anti-infective drug therapy with
      or without SRP compared to SRP alone on changes in clinical, patient-centered,
      and adverse outcomes? SEARCH PROTOCOL: MEDLINE, the Cochrane Central Trials
      Register, and Web of Science were searched. Hand searches were performed of the
      Journal of Clinical Periodontology, Journal of Periodontology, and Journal of
      Periodontal Research. Searches were performed for articles published through
      April 2002. In addition, investigators contacted editors of the above-mentioned
      journals and companies sponsoring research on these agents for related
      unpublished data and studies in progress. SELECTION CRITERIA:  INCLUSION
      CRITERIA: Studies included randomized controlled clinical trials (RCT), and case
      controlled and cohort studies at least 3 months long. Therapeutic interventions
      had to include 1) SRP alone; 2) local anti-infective drug therapy and SRP; or 3)
      local anti-infective drug therapy alone. Included studies had to report patient
      based mean values and measures of variation for probing depth (PD) and/or
      clinical attachment levels (CAL) for both test and control groups. EXCLUSION
      CRITERIA: Studies were excluded if they: 1) included data from a previously
      published article; 2) included daily rinsing with chlorhexidine (CHX); or 3) had
      unclear descriptions of randomization procedures, examiner masking, or
      concomitant therapies. DATA COLLECTION AND ANALYSIS: For the meta-analysis, PD
      and CAL were expressed as summary mean effects with 95% confidence intervals (CI)
      for the effect, and analyzed using a standardized difference between SRP alone
      and experimental agent groups. The results were assessed with both fixed-effects
      and random-effects models. Studies were ranked according to the York system. MAIN
      RESULTS: 1. Thirty-two studies were included (28 RCT, 2 cohort, and 2 case
      control), incorporating a total patient population of 3,705 subjects. 2.
      Essentially all studies reported substantial reductions in gingival inflammation
      and bleeding indices, which were similar in both control and experimental groups.
      3. A meta-analysis completed on 19 studies that included SRP and local sustained
      release agents compared with SRP alone indicated significant adjunctive PD
      reduction or CAL gain for minocycline (MINO) gel, microencapsulated MINO, CHX
      chip and doxycycline (DOXY) gel during SRP compared to SRP alone. 4. Use of
      antimicrobial irrigants or anti-infective sustained-release systems as an adjunct
      to SRP does not result in significant patient-centered adverse events. REVIEWERS'
      CONCLUSIONS: 1. In some populations, anti-infective agents in a sustained-release
      vehicle alone can reduce PD and bleeding on probing (BOP) equivalent to that
      achieved by SRP alone. 2. No evidence was found for an adjunctive effect on
      reduction of PD and BOP of therapist-delivered CHX irrigation during SRP compared
      to SRP alone. 3. Additional RCTs are needed which evaluate the effectiveness of
      these therapies in all forms of periodontitis. 4. The study protocol for future
      RCTs should include appropriate statistical analyses and complete data sets to
      facilitate future evidence-based reviews. 5. Alternative surrogate parameters to
      PD and CAL need to be identified and validated such as microbial, inflammatory,
      or tissue-destructive markers that could be used in conjunction with clinical
      parameters to help determine the patient's response to emerging technologies that
      target the infectious and/or inflammatory aspects of periodontitis. 6. Future
      Phase IV clinical trials should be designed that evaluate local anti-infective
      therapies in conjunction with SRP in a manner consistent with current standards
      of care and evaluate cost-effectiveness. 7. The use of local anti-infective
      agents in at-risk patient populations and for the treatment of at-risk disease
      sites needs to be validated in randomized controlled clinical trials. 8. Several
      local anti-infective agents combined with SRP appear to provide additional
      benefits in PD reduction and CAL gain compared to SRP alone. The decision to use
      local anti-infective adjunctive therapy remains a matter of individual clinical
      judgment, the phase of treatment, and the patient's status and preferences.

PMID- 14971251
TI  - Local anti-infective therapy: mechanical and physical approaches. A systematic
      review.
AB  - BACKGROUND: Although mechanical non-surgical therapy (scaling and root planing)
      is the most common means of initial treatment of periodontal diseases, the
      relative clinical efficacy of various methods, including manual versus machine
      driven, with or without adjunctive agents, has not been determined. RATIONALE:
      This systematic review analyzes the literature in an effort to identify the most
      effective therapies, based on both clinical and patient-centered outcomes.
      FOCUSED QUESTION: In patients with periodontitis, what is the effect of
      mechanically-driven instrumentation (e.g., power-driven) and/or subgingival
      irrigation with and without manual instrumentation compared to manual
      instrumentation alone? SEARCH PROTOCOL: Two investigators examined MEDLINE and
      the Cochrane Oral Health Group specialized registry for clinical trials published
      in English. Hand searches were performed of the International Journal of
      Periodontics & Restorative Dentistry, Journal of Clinical Periodontology, Journal
      of Periodontology, and Journal of Periodontal Research. Searches were performed
      for articles published through April 2002. Editors of these journals were asked
      to provide information on articles currently under review. In addition, an
      electronic discussion group on periodontal diseases and treatment was contacted,
      as were manufacturers of manual and mechanical instruments and of adjunctive
      agents. SELECTION CRITERIA:  INCLUSION CRITERIA: Only randomized clinical trials,
      cohort studies, or case-control studies at least 3 months long were included. All
      studies had to compare manual instrumentation (MI; scaling and root planing
      [SRP]) alone with some other form of non-surgical therapy. These included MI
      versus mechanically-driven instruments (MDI) alone; MI versus MI plus MDI; MI
      versus MDI plus an agent (e.g., chlorhexidine); and MI versus subgingival
      irrigation (SGI) delivered in conjunction with MI or MDI. EXCLUSION CRITERIA:
      Studies not meeting the inclusion criteria or those treating periodontal diseases
      as a manifestation or complication of some other disease or disorder were not
      included. DATA COLLECTION AND ANALYSIS: Probing depth, clinical attachment level,
      bleeding on probing, and gingival recession were the primary outcomes. Because of
      the heterogeneity of the patient populations, treatments, and outcome measures,
      meta-analysis was not appropriate. Only in-study data were compared. Four of the
      studies required extrapolating data from figures and graphs, resulting in
      questionable accuracy. MAIN RESULTS: 1. Nine studies, representing a study
      population of 129, were included in the review. 2. Five studies compared MI with
      MDI alone. The other 4 compared MI alone to MI plus SGI or subgingival tissue
      treatment. 3. There was comparable efficacy between MI and MDI when treating
      single-rooted teeth. 4. The use of SGI or subgingival tissue treatment as an
      adjunct to MI provided no additional benefit compared to MI alone. 5. Findings
      reported in the review must be interpreted with considerable caution, as lack of
      study heterogeneity made meta-analysis unfeasible and the need to extrapolate
      outcomes values from graphs and figures may have resulted in some inaccuracy.
      REVIEWERS' CONCLUSIONS: 1. Manual and mechanically-driven instrumentation appears
      comparable in affecting improved clinical outcomes. 2. Instrumentation time for
      MI and MDI were similar, except for 1 study in which MDI was significantly
      shorter. 3. Adjunctive SGI plus MI and subgingival tissue treatment result in
      similar clinical outcomes when compared to MI alone. 4. If study data are to be
      effectively and analytically combined to facilitate meaningful comparisons of
      treatment outcomes, detailed and standardized study designs must be developed and
      used consistently in clinical trials.

PMID- 14971252
TI  - Systemic anti-infective periodontal therapy. A systematic review.
AB  - BACKGROUND: Periodontal diseases are infections and thus systemically
      administered antibiotics are often employed as adjuncts for their control. There
      are conflicting reports as to whether these agents provide a therapeutic benefit.
      RATIONALE: The purpose of this systematic review is to determine whether
      systemically administered antibiotics improve a primary clinical outcome measure,
      periodontal attachment level change. FOCUSED QUESTION: In patients with
      periodontitis, what is the effect of systemically administered antibiotics as
      compared to controls on clinical measures of attachment level? SEARCH PROTOCOL:
      The Pub/Med database was searched from 1966 to May 2002. Searches were limited to
      human studies published in English. Hand searches were performed on the Journal
      of Clinical Periodontology, Journal of Periodontology, and Journal of Periodontal
      Research. References in relevant papers and review articles were also examined.
      SELECTION CRITERIA:  INCLUSION CRITERIA: Trials were selected if they met the
      following criteria: randomized controlled clinical trials, quasi-experimental
      studies, and cohort studies of > 1 month duration with a comparison group;
      subjects with aggressive, chronic, or recurrent periodontitis and periodontal
      abscess; use of a single or a combination of systemically administered
      antibiotics(s) versus non-antibiotic therapy; and a primary outcome of mean
      attachment level change (AL). EXCLUSION CRITERIA: Studies involving the use of
      low-dose doxycycline, combinations of locally plus systemic antibiotics, or where
      the control group included a systemically administered antibiotic were excluded.
      DATA COLLECTION AND ANALYSIS: A mean difference in AL between groups was
      available for all papers used in the meta-analysis. A standard deviation (SD) for
      the difference was used if provided or calculated from the SD or standard error
      of the mean (SEM) when provided for single measurements. Data were subset by
      antibiotic employed, type of adjunctive therapy, and disease type. Results were
      assessed with both fixed-effects and random-effects models. MAIN RESULTS: 1.
      Twenty-nine studies, 26 RCTs and 3 quasi-experimental (36 comparisons), met the
      entry criteria. Total study population, both control and test groups, was
      estimated at over 1,200. 2. Twenty-two studies (27 comparisons) were used in the
      meta-analysis, evaluating if the antibiotics provided a consistent benefit in
      mean AL change for different patient populations, for different therapies, and
      for different antibiotics. 3. For the majority of the comparisons, systemically
      administered antibiotics exhibited a more positive attachment level change than
      the control group in the study. The combined results were statistically
      significant (P < 0.001). 4. The systemic antibiotics were uniformly beneficial in
      providing an improvement in AL when used as adjuncts to scaling and root planing
      (SRP) and were consistently beneficial, although of borderline significance, when
      used as adjuncts to SRP plus surgery or as a stand alone therapy. 5. When
      examining the effects of individual or combinations of antibiotics, it was found
      that there were statistically significant improvements in AL for tetracycline,
      metronidazole, and an effect of borderline statistical significance for the
      combination of amoxicillin plus metronidazole. 6. Improvements in mean AL were
      consistent for both chronic and aggressive periodontitis subjects, although the
      aggressive periodontitis patients benefited more from the antibiotics. REVIEWERS'
      CONCLUSIONS: 1. The use of systemically administered adjunctive antibiotics with
      and without SRP and/or surgery appeared to provide a greater clinical improvement
      in AL than therapies not employing these agents. 2. The data supported similar
      effect sizes for the majority of the antibiotics; therefore, the selection for an
      individual patient has to be made based on other factors. 3. Due to a lack of
      sufficient sample size for many of the antibiotics tested, it is difficult to
      provide guidance as to the more effective ones.

PMID- 14971253
TI  - Microbial identification in the management of periodontal diseases. A systematic
      review.
AB  - BACKGROUND: Our understanding of the complexity of the oral microbiota continues
      to improve as new technologies, such as the analysis of 16S rRNA bacterial genes,
      are utilized. Despite the difficult of cataloguing all microorganisms and
      determining their pathogenic potential, some species, mostly members of the
      resident oral microbiota, have been identified as likely periodontal pathogens.
      However, for microbial diagnosis to be of value, it needs to affect disease
      diagnosis and/or treatment planning as well as result in superior treatment
      outcomes and/or provide an economic benefit to the patient. RATIONALE: The
      purposes of this systematic review were to determine if microbial identification
      influences periodontal patient management and whether treatment outcomes are
      better compared to patients whose treatment plans are developed without this
      information. FOCUSED QUESTION: In patients with periodontal diseases, does
      microbial identification influence patient management compared to treatment
      prescribed without this information? SEARCH PROTOCOL: The MEDLINE database was
      searched for clinical studies in English from 1991 through 2002 by 2
      investigators. Hand searches were performed on the Journal of Clinical
      Periodontology, Journal of Periodontology, Journal of Periodontal Research, Oral
      Microbiology and Immunology, and Periodontology 2000. In addition, directors of
      diagnostic laboratories were contacted about unpublished data. SELECTION
      CRITERIA:  INCLUSION CRITERIA: Articles in which bacterial identification
      influenced patient treatment were preferred as were those reporting longitudinal
      data demonstrating a direct relationship between the presence or absence of
      certain bacteria and subsequent alterations in clinical variables. Because of the
      limited number of studies, all articles, including case reports, were considered.
      EXCLUSION CRITERIA: Review articles without original data were excluded, although
      references were examined for possible inclusion. Articles reporting data showing
      associations between certain microorganisms and disease or health that did not
      affect treatment were excluded. Clinical trials testing antibacterial agents for
      their ability to enhance mechanical debridement were not included since bacterial
      identification had little effect on drug selection or experimental group
      assignment. Articles dealing with implants rather than natural teeth were
      omitted. DATA ANALYSIS AND COLLECTION: The heterogeneity of the published data
      precludes any meaningful pooling of data or meta-analysis. The pertinent
      literature, including relevant variables of plaque, gingivitis, and bleeding on
      probing scores; probing depth; clinical attachment level; number of lost teeth;
      and microbial changes; and patient-centered outcomes including decrease in
      morbidity, reduced need for surgery, and duration and cost of treatment are
      summarized. MAIN RESULTS: 1. There was a lack of articles with a high evidence
      rating; most pertinent articles were either case reports or case series without
      controls. 2. Because reports were heterogeneous regarding study design, patient
      selection, and data collection, meta-analysis was not feasible and results are
      summarized in tabular format. 3. This report is based on a total of 24 studies,
      representing a total patient population of approximately 835. 4. Thirteen studies
      reported on microbiological identification as an aid in treatment planning. 5.
      Eleven studies reported a differential clinical response depending on the
      detection or lack of detection of specific organisms. REVIEWERS' CONCLUSIONS: 1.
      The published material suggests that microbiological monitoring may be useful in
      management of selected patients who do not respond to standard therapy. 2. Some
      practitioners consider microbial identification a valuable adjunct to managing
      patients with certain forms of periodontitis, although there is a lack of strong
      evidence to this effect. 3. Additional research is needed to address this issue.

PMID- 14971254
TI  - Growth and amelogenin-like factors in periodontal wound healing. A systematic
      review.
AB  - BACKGROUND: Regeneration of tooth-supporting structures destroyed by
      periodontitis is a major goal of periodontal therapy. Periodontal tissue
      engineering utilizing growth and amelogenin-like factors (GAFs) applies advances
      in materials science and biology to regenerate alveolar bone, periodontal
      ligament, and cementum. Amelogenin-like factors (e.g., enamel matrix derivative
      [EMD]) and growth factors (e.g., platelet-derived growth factor [PDGF] and bone
      morphogenetic proteins [BMPs, also considered morphogens]) have demonstrated
      pleotrophic effects on the stimulation of several key events required for tissue
      regeneration including DNA synthesis, chemotaxis, differentiation, and matrix
      synthesis. RATIONALE: GAFs have been used for the treatment of periodontal
      disease as shown in preclinical and clinical studies. This systematic review
      evaluates the evidence to support the utilization of EMD and growth factors (GFs)
      for periodontal repair and regeneration associated with natural teeth. FOCUSED
      QUESTION: In patients with periodontal osseous defects, what is the effect of
      GAFs compared with controls on clinical, radiographic, histologic, adverse, and
      patient-centered outcomes? SEARCH PROTOCOL: Two investigators searched MEDLINE,
      pre-MEDLINE, and the Cochrane Oral Health Group trials register for clinical and
      preclinical studies published in English. Hand searches were performed on the
      International Journal of Periodontics and Restorative Dentistry, Journal of
      Clinical Periodontology, Journal of Dental Research, Journal of Periodontology,
      and Journal of Periodontal Research. Searches were performed for articles
      published through April 2002. In addition, investigators contacted manufacturers
      of GAF products for related unpublished data and studies in progress. SELECTION
      CRITERIA:  INCLUSION CRITERIA: Randomized controlled clinical trials (RCTs),
      cohort studies, case-control studies, case reports, and preclinical (animal)
      randomized controlled investigations that included a cohort population diagnosed
      with periodontal disease and presenting data on intrabony/interproximal defects
      and/or furcation defects were screened. EXCLUSION CRITERIA: In vitro studies or
      those that did not include quantifiable data with respect to clinical or bone
      measures were not included. DATA COLLECTION AND ANALYSIS: Meta-analyses were
      performed for studies that fulfilled the eligibility criteria for the following
      continuous variables: clinical attachment level (CAL), probing depth (PD), or
      bone level (radiographic, re-entry, or histologic). Heterogeneity was assessed to
      determine whether the differences among therapies were due to systematic
      confounding factors (as noted in study quality assessments). MAIN RESULTS: 1.
      Eight studies, representing 7 RCTs and 1 quasi-experimental study, representing a
      total population of 511 subjects were analyzed with respect to EMD. 2. The
      majority of the remaining papers had a low evidence rating. 3. Most reports were
      case studies or case series without controls. 4. There were insufficient data to
      conduct a meta-analysis on the effect of growth factors used in periodontal
      repair around teeth. REVIEWERS' CONCLUSIONS: 1. There is evidence supporting the
      use of EMD for periodontal osseous defects to improve CAL and reduce PD, although
      long-term benefits have not been established. 2. EMD has demonstrated notable
      consistency among the studies investigated in terms of superiority to controls
      (in general compared to open flap debridement [OFD]). 3. EMD appears to be safe
      for single and multiple administrations in terms of lack of elicitation of
      antibody responses or other local/systemic inflammatory events. 4. Preclinical
      and initial clinical data for growth factors appear promising but are
      insufficient to draw definitive conclusions at this time.

PMID- 14971255
TI  - Efficacy of chemical root surface modifiers in the treatment of periodontal
      disease. A systematic review.
AB  - BACKGROUND: Periodontal regeneration has been a relentless goal of the
      periodontist. Perhaps the oldest and most frequently attempted type of
      regeneration has involved chemical modification of the root surface. Varying
      results from histological and clinical studies have created controversy about the
      clinical effectiveness of root surface decalcification. RATIONALE: This
      systematic review assesses the efficacy of root surface biomodification through
      the use of citric acid, tetracycline, or ethylenediaminetetraacetic acid (EDTA)
      in patients with chronic periodontitis. FOCUSED QUESTION: Does the use of
      chemical root declacification result in effective periodontal regeneration and
      improved clinical outcomes in patients with chronic periodontitis? SEARCH
      PROTOCOL: The Cochrane Database of Systematic Reviews; Database of Abstracts of
      Reviews of Effectiveness; Cochrane Central Register of Controlled Trials;
      American College of Physicians Journal Club, evidence-based MEDLINE journals; and
      National Center for Biotechnology Information PubMed Journals, as well as
      Dogpile, Google, and Copernic search engines were screened. Hand searches were
      performed on the Journal of Clinical Periodontology, Journal of Periodontology,
      Journal of Periodontal Research, and Periodontology 2000. Searches were performed
      for relevant clinical trials published through September 25, 2002. SELECTION
      CRITERIA:  INCLUSION CRITERIA: Histological and clinical studies evaluating the
      effects of citric acid, tetracycline, or EDTA on root surfaces of patients with
      chronic periodontitis were considered for inclusion. EXCLUSION CRITERIA: Studies
      evaluating extracellular matrix proteins (e.g., fibronectin), enamel matrix
      proteins (e.g., amelogenins), or other proteins or growth factors applied to the
      root surface were not included. DATA COLLECTION AND ANALYSIS: Primary outcome
      measures included changes in connective tissue attachment, cementogenesis,
      clinical attachment levels, probing depths, and gingival recession. Secondary
      outcome measures included changes in bone level, gingival inflammation, and
      plaque levels. Results for continuous outcome measures for primary variables
      (clinical attachment levels, probing depths, and recession) were expressed as
      mean differences or standardized mean differences. Clinical attachment levels and
      reduction in probing depth were evaluated using meta-analysis. All papers were
      rated according to methodological strength of evidence. MAIN RESULTS: 1. Thirty
      four studies incorporating a total patient population of 575 were analyzed: 26
      for citric acid, 5 for tetracycline, and 3 for EDTA treatment. 2. Four of 8 human
      histological studies reported regeneration with the use of citric acid. Only 1 of
      18 clinical studies reported attachment gain. 3. Of the 5 studies examined using
      tetracycline, 1 histological study and 1 clinical study reported attachment gain.
      4. No regeneration was reported in the 3 studies evaluating the use of EDTA. 5.
      Meta-analysis performed on 28 clinical trials did not show any significant
      effects of acid root treatment on attachment level gains or probing depth.
      REVIEWER'S CONCLUSIONS: 1. Evidence to date suggests that the use of citric acid,
      tetracycline, or EDTA to modify the root surface provides no benefit of clinical
      significance to regeneration in patients with chronic periodontitis. 2. The best
      method for ascertaining the clinical efficacy of acid-treated root regeneration
      would be to conduct a randomized clinical trial with sufficient statistical power
      that is supported by quantitative histological evaluation. 3. The majority of the
      studies that evaluated the regenerative potential of root surface modifiers were
      observational in nature; therefore, the value of conclusions reached in this
      manuscript must be carefully considered.

PMID- 14971256
TI  - The efficacy of bone replacement grafts in the treatment of periodontal osseous
      defects. A systematic review.
AB  - BACKGROUND: Bone replacement grafts (BRG) are widely used in the treatment of
      periodontal osseous defects; however, the clinical benefits of this therapeutic
      practice require further clarification through a systematic review of randomized
      controlled studies. RATIONALE: The purpose of this systematic review is to access
      the efficacy of bone replacement grafts in proving demonstrable clinical
      improvements in periodontal osseous defects compared to surgical debridement
      alone. FOCUSED QUESTION: What is the effect of bone replacement grafts compared
      to other interventions on clinical, radiographic, adverse, and patient-centered
      outcomes in patients with periodontal osseous defects? SEARCH PROTOCOL: The
      computerized bibliographical databases MEDLINE and EMBASE were searched from 1966
      and 1974, respectively, to October 2002 for randomized controlled studies in
      which bone replacement grafts were compared to other surgical interventions in
      the treatment of periodontal osseous defects. The search strategy included
      screening of review articles and reference lists of retrieved articles as well as
      hand searches of selected journals. INCLUSION CRITERIA: All searches were limited
      to human studies in English language publications. EXCLUSION CRITERIA: Non
      randomized observational studies (e.g., case reports, case series), publications
      providing summary statistics without variance estimates or data to permit
      computation, and studies without BRG intervention alone were excluded. DATA
      COLLECTION AND ANALYSIS: The therapeutic endpoints examined included changes in
      bone level, clinical attachment level, probing depth, gingival recession, and
      crestal resorption. For purposes of meta-analysis, change in bone level (bone
      fill) was used as the primary outcome measure, measured upon surgical re-entry or
      transgingival probing (sounding). MAIN RESULTS: 1. Forty-nine controlled studies
      met eligibility criteria and provided clinical outcome data on intrabony defects
      following grafting procedures. 2. Seventeen studies provided clinical outcome
      data on BRG materials for the treatment of furcation defects. REVIEWERS'
      CONCLUSIONS: 1. With respect to the treatment of intrabony defects, the results
      of meta-analysis supported the following conclusions: 1) bone grafts increase
      bone level, reduce crestal bone loss, increase clinical attachment level, and
      reduce probing depth compared to open flap debridement (OFD) procedures; 2) No
      differences in clinical outcome measures emerge between particulate bone
      allograft and calcium phosphate (hydroxyapatite) ceramic grafts; and 3) bone
      grafts in combination with barrier membranes increase clinical attachment level
      and reduce probing depth compared to graft alone. 2. With respect to the
      treatment of furcation defects, 15 controlled studies provided data on clinical
      outcomes. Insufficient studies of comparable design were available to submit data
      to meta-analysis. Nonetheless, outcome data from these studies generally
      indicated positive clinical benefits with the use of grafts in the treatment of
      Class II furcations. 3. With respect to histological outcome parameters, 2
      randomized controlled studies provide evidence that demineralized freeze-dried
      bone allograft (DFDBA) supports the formation of a new attachment apparatus in
      intrabony defects, whereas OFD results in periodontal repair characterized
      primarily by the formation of a long junctional epithelial attachment. Multiple
      observational studies provide consistent histological evidence that autogenous
      and demineralized allogeneic bone grafts support the formation of new attachment.
      Limited data also suggest that xenogenic bone grafts can support the formation of
      a new attachment apparatus. In contrast, essentially all available data indicate
      that alloplastic grafts support periodontal repair rather than regeneration. 4.
      The results of this systematic review indicate that bone replacement grafts
      provide demonstrable clinical improvements in periodontal osseous defects
      compared to surgical debridement alone.

PMID- 14971257
TI  - Guided tissue regeneration for the treatment of periodontal intrabony and
      furcation defects. A systematic review.
AB  - BACKGROUND: Many clinical studies have demonstrated that guided tissue
      regeneration (GTR) is a successful treatment modality of periodontal
      reconstructive surgery and it has become an accepted procedure in most
      periodontal practices. RATIONALE: The purpose of this structured review was to
      assess the efficacy of guided tissue regeneration (GTR) procedures in patients
      with periodontal osseous defects compared with surgical controls on clinical,
      radiographic, adverse, and patient-centered outcomes. It extends the scope of
      previous GTR systematic reviews, which were limited to randomized controlled
      studies, by the scope of outcome measures examined, and the duration of the
      study. FOCUSED QUESTION: In patients with periodontal osseous defects, what is
      the effect of physical barriers compared with surgical controls on clinical,
      radiographic, adverse, and patient-centered outcomes? SEARCH PROTOCOL: An
      electronic search of the Cochrane Oral Health Group Trials Register and MEDLINE
      databases was performed. Manual searching of journals included Journal of
      Clinical Periodontology, Journal of Periodontology, and Journal of Periodontal
      Research up to January 2002. This manual search also included review of relevant
      bibliographies. Two manufacturers of GTR devices were contacted regarding
      unpublished data. SELECTION CRITERIA:  INCLUSION CRITERIA: Studies were selected
      for review if the evidence level was 3B (cohort) or above, at least 6 months
      duration, and compared a test GTR intervention with a surgical control. EXCLUSION
      CRITERIA: Studies with experimental design problems; histologic or
      microbiological investigations; or those with outcome measurements, study
      populations, or study duration not consistent with the inclusion criteria were
      excluded. Primary outcome measures for intrabony defects were: clinical
      attachment level (CAL) gain, probing depth reduction (PD), gingival recession
      (REC) reduction; for furcation defects: vertical probing attachment level (VPAL)
      gain, vertical probing depth reduction (VPD), horizontal probing depth reduction
      (HPD), horizontal open probing attachment level gain (HOPA), and vertical open
      probing attachment level gain (VOPA). Meta-analysis was performed to compare GTR
      procedures to other surgical treatments and to examine the resulting clinical
      outcomes. MAIN RESULTS: 1. For the primary outcome variables, in both intrabony
      defect and furcation-defect studies, GTR was favored over open flap debridement
      (OFD) therapies (P < 0.0001). 2. No differences were detected among barrier
      types, but barrier types could explain some heterogeneity in the results. 3.
      Augmentation of the GTR barrier with a particulate graft enhanced VPD (P < 0.05),
      VPAL, and HOPA, but none of the intrabony outcomes. REVIEWER'S CONCLUSIONS:
      Overall, GTR is consistently more effective than OFD in the gain of clinical
      attachment and probing depth reduction in the treatment of intrabony and
      furcation defects.

PMID- 14971258
TI  - Surgical therapies for the treatment of gingival recession. A systematic review.
AB  - BACKGROUND: A variety of soft tissue augmentation procedures directed at root
      coverage have been documented in the literature utilizing autogenous or allogenic
      soft tissue grafting or guided tissue regeneration (GTR). RATIONALE: The purpose
      of this systematic review was to assess the literature regarding the efficacies
      of various surgical gingival augmentation procedures relative to clinical and
      patient-oriented outcomes. FOCUSED QUESTION: What is the effect of surgical
      therapy for root coverage in patients with gingival recession compared with other
      treatment modalities or baseline values? SEARCH PROTOCOL: PubMed and the Cochrane
      Oral Health Group Trials Register were searched to identify human studies in
      English investigating the therapeutic use of a soft tissue surgical procedure to
      treat gingival recession. Searches were performed for articles published by April
      2002. SELECTION CRITERIA: Initial screening of identified abstracts accepted all
      studies evaluating surgical intervention of gingival recession. Independent
      review by 2 reviewers evaluated full-text reports regarding study
      characteristics. Only those studies determined to be randomized clinical trials
      (RCTs) were included in the final analysis. DATA ANALYSIS AND COLLECTION: Outcome
      measures included changes in root coverage, clinical attachment levels (CAL),
      probing depth (PD), and width of keratinized tissue (KT). The only data suitable
      for meta-analysis were comparisons of the efficacy of connective tissue grafts
      with GTR. MAIN RESULTS: 1. Thirty-two articles (total study population: 687) met
      the criteria for RCTs: 11 (population: 286) related to various autogenous soft
      tissue augmentation procedures; 18 (population: 360) to GTR; and 3 (population:
      41) to allogenic soft tissue augmentation. 2. Meta-analysis identified greater
      gains in both root coverage and keratinized tissue width for connective tissue
      graft procedures compared to GTR. 3. No other data were compatible with meta
      analysis. REVIEWERS' CONCLUSIONS: 1. Soft tissue augmentation procedures are
      effective means of obtaining root coverage. 2. Connective grafting techniques
      appear to have an advantage over GTR. 3. There is a need for further efficacy
      studies and for investigation of these procedures relative to patient-oriented
      outcomes such as esthetics, root sensitivity, and postoperative morbidities.

PMID- 14971259
TI  - Localized ridge augmentation/preservation. A systematic review.
AB  - BACKGROUND: Osseointegrated implants have been documented as efficacious,
      however, their placement may be contraindicated in some patients due to
      insufficient bone volume. Techniques such as guided bone regeneration (GBR),
      immediate implantation, and distraction osteogenesis (DO) have been utilized as
      ridge enhancement therapies. RATIONALE: This systematic review evaluates dental
      implant survival rates in patients treated with ridge augmentation or
      preservation techniques. FOCUSED QUESTION: In patients requiring dental implant
      placement, what is the effect of localized ridge preservation versus implant
      placement without augmentation on implant survival and adverse effects? SEARCH
      PROTOCOL: MEDLINE and Cochrane Oral Health Group Specialized Trial Register were
      searched. Hand searches were performed on Clinical Oral Implants Research,
      International Journal of Oral and Maxillofacial Implants, International Journal
      of Periodontics and Restorative Dentistry, Journal of Clinical Periodontology,
      Journal of Periodontology, and Journal of Periodontal Research. All searches were
      performed for articles published through April 2002. SELECTION CRITERIA:
      Publications reporting survival rate of dental implants following ridge therapy
      were included in the analysis. Reports describing techniques were excluded. DATA
      COLLECTION AND ANALYSIS: Due to the absence of controlled studies, a meta
      analysis was not performed. Descriptive statistics are used to report the data.
      MAIN RESULTS: 1. A total of 18 studies were included: 13 reporting on guided bone
      regeneration (GBR, 1,741 patients) and 5 on distraction osteogenesis (DO, 92
      patients). 2. There is a high level of predictable implant survival in sites
      treated by GBR or DO. 3. These survival rates are similar to those of implants
      placed in native bone. REVIEWERS' INTERPRETATIONS: Survival rates were similar
      for both GBR and DO implants. These survival rates were similar to implants
      placed in native bone.

PMID- 14971260
TI  - Effect of maxillary sinus augmentation on the survival of endosseous dental
      implants. A systematic review.
AB  - BACKGROUND: Grafting the floor of the maxillary sinus has become the most common
      surgical intervention for increasing alveolar bone height prior to the placement
      of endosseous dental implants in the posterior maxilla. Outcomes of this
      procedure may be affected by specific surgical techniques, simultaneous versus
      delayed implant placement, use of barrier membranes over the lateral window,
      selection of graft material, and the surface characteristics and the length and
      width of the implants. RATIONALE: The primary objective of this systematic review
      was to determine the efficacy of the sinus augmentation procedure and compare the
      results achieved with various surgical techniques, grafting materials, and
      implants. FOCUSED QUESTION: In patients requiring dental implant placement, what
      is the effect on implant survival of maxillary sinus augmentation versus implant
      placement in the non-grafted posterior maxilla? SEARCH PROTOCOL: MEDLINE, the
      Cochrane Oral Health Group Specialized Trials Register, and the Database of
      Abstracts and Reviews of Effectiveness were searched for articles published
      through April 2003. Hand searches were performed on Clinical Oral Implants
      Research, International Journal of Oral and Maxillofacial Implants, and the
      International Journal of Periodontics & Restorative Dentistry and the
      bibliographies of all relevant papers and review articles. In addition,
      researchers, journal editors, and industry sources were contacted to see if
      pertinent unpublished data that had been accepted for publication were available.
      SELECTION CRITERIA:  INCLUSION CRITERIA: Human studies with a minimum of 20
      interventions, a minimum follow-up period of 1-year loading, an outcome
      measurement of implant survival, and published in English, regardless of the
      evidence level, were considered. EXCLUSION CRITERIA: Studies involving multiple
      simultaneous interventions (e.g., simultaneous ridge augmentation) and studies
      with missing data that could not be supplied by the study authors were excluded.
      DATA COLLECTION AND ANALYSIS: Where adequate data were available, subgroups of
      dissimilar interventions (e.g., surgical techniques, graft materials, implant
      surfaces, membranes) were isolated and subjected to meta-regression, a form of
      meta-analysis. MAIN RESULTS: 1. Forty-three studies, 3 randomized controlled
      clinical trials (RCTs), 5 controlled trials (CTs), 12 case series (CS), and 23
      retrospective analyses (RA) were identified. Thirty-four were lateral window
      interventions, 5 were osteotome interventions, 2 were localized management of the
      sinus floor, and 2 involved the crestal core technique. 2. Meta-regression was
      performed to determine the effect of the variables of block versus particulate
      grafting techniques, implant surface, graft material, and the use of a membrane
      over the lateral window. 3. The survival rate of implants placed in sinuses
      augmented with the lateral window technique varied between 61.7% and 100%, with
      an average survival rate of 91.8%. For lateral window technique: 4. Implant
      survival rates reported in this systematic review compare favorably to reported
      survival rates for implants placed in the non-grafted posterior maxilla. 5. Rough
      surfaced implants have a higher survival rate than machine-surfaced implants when
      placed in grafted sinuses. 6. Implants placed in sinuses augmented with
      particulate grafts show a higher survival rate than those placed in sinuses
      augmented with block grafts. 7. Implant survival rates were higher when a
      membrane was placed over the lateral window. 8. The utilization of grafts
      consisting of 100% autogenous bone or the inclusion of autogenous bone as a
      component of a composite graft did not affect implant survival. 9. There was no
      statistical difference between the covariates of simultaneous versus delayed
      implant placement, types of rough-surfaced implants, length of follow-up, year of
      publication, and the evidence level of the study. REVIEWERS' CONCLUSIONS:
      Insufficient data were present to statistically evaluate the effects of smoking,
      residual crestal bone height, screw versus press-fit implant design, or the
      effect of implant surface micromorphology other than machined versus rough
      surfaces. There are insufficient data to recommend the use of platelet-rich
      plasma in sinus graft surgery.

PMID- 14971261
TI  - [The role of scintigraphy in the diagnosis of mandibular bone changes].
AB  - Investigating the scintigraphic images of jaws may have a diagnostic value of
      bone alterations of dental origin. Anterior view of whole body bone scintigraphy
      revealed hot spot on jaws of 61% (279) of patients. Twenty-six patients (mean age
      58.3 year) from all of those who had increased tracer uptake (ITU) in the maxillo
      mandibular region were called back for dental examination. 279 out of 459 (61%)
      patients had ITU in the maxillo-mandibular region. Dental examination revealed
      the dental origin of ITU in all cases. In case of periapical pathosis tracer
      uptake showed 28.79% increase compared to the contralateral side. In marginal
      periodontitis 23.82% ITU was found. In case of loading due to prosthesis 13.06%
      ITU was observed. The mean DMF-T value was 26.36 +/- 4.52 (D = 4.12, M = 20.8, F
      = 1.44). The prosthetic index was 0.42 on the mandible. The above mentioned data
      mean very low oral health conditions of the patients included in this
      examination. The results show that bone scintigraphy is a valuable procedure in
      detecting tooth related jaw lesions. Bone scintigraphy provides very useful data
      on oral health of these patients. Enrolling of these patients into regular dental
      care is inevitable.

PMID- 14971262
TI  - [Prevalence of talon cusp in patients aged 7-18].
AB  - Talon cusp is an uncommon malformation. The aetiology is unknown although it is
      thought to be the combination of genetic and environmental factors. The purpose
      of the study was to examine the prevalence of talon cusps in children aged 7-18.
      600 model casts were examined in the Pedodontic and Orthodontic Department of the
      Semmelweis University. Classification of talon cusps used was based on the degree
      of formation and extension by Hattab et al [6]. 12 talon cusps were found in the
      group of type 1, two were found in group of type 2 and one in type 3. The
      prevalence of talon cusps was 2.5%, mostly on the upper permanent lateral
      incisors. In four cases it was bilateral. The prevalence of talon cusps was more
      frequent in males compared to females. The early recognition of the anomaly is
      important from the therapeutic point of view (placement of sealant, periodic
      reduction of the cusp).

PMID- 14971263
TI  - [The Hungarian version of the "Dental Beliefs Survey (DBS)--preliminary data in
      the Hungarian population].
AB  - The Hungarian version of DBS was analysed on 100 participants (64 females, 36
      males, mean age: 36.4 +/- 14.3) from 5 subgroups: dental students (n = 20), other
      intellectuals (n = 20), dental nurses (n = 19), dental patients (n = 20), family
      doctor's patients (n = 21). Mean values were: DBS: 29.1 +/- 10.8; DAS: 10.6 +/-
      3.9; DFS: 39.0 +/- 16.7. Family doctor's patients scored higher (p < or = 0.05)
      on DBS than all other groups, and dental students scored lower on DBS than all
      other groups (p < or = 0.05; except other intellectuals). DBS scores of age group
      between 21-30 yrs. differed significantly from age groups 31-40 yrs. (p < or =
      0.05) and 41-50 yrs. (p < or = 0.01). There were no differences related to gender
      and marital status related to DBS scores. Positive Pearson's correlation (p < or
      = 0.05) of DBS was stronger related to dental anxiety scores (DAS: r = 0.56, DFS:
      r = 0.63) than related to general anxiety scores, whereas Pearson's correlation
      between DAS and DFS scores was even more prominent (r = 0.82, p < or = 0.05).

PMID- 14971264
TI  - [Comparison of interfaces between a NiCr alloy and various dental ceramics using
      transmission electron microscopy (TEM) and 3-point bending test].
AB  - Several methods (e.g. tensile strength, shear bond strength) have been used in
      testing metal-ceramic bonds. However, in the interface, structural and analytical
      investigations can be applied in determining the chemical and phase structure of
      substances making up the bond. The aim of the present study is to assess the
      interface between Wiron 99 (Bego) alloy and Vision (Wohlwend) VITA VMK68 (Vita),
      Carat (Dentsply/DeTrey) ceramic using transmission electron microscopy (TEM) and
      3-point bending test. In the case of NiCr alloys, morphologically similar but
      structurally varying phases developed in all of the ceramics. In each case, a
      Cr2O3 layer consisting of small crystals (10-20 nm) was noticed with a series of
      underlying bubble-like amorphous inclusions. The exact three dimensional (3D)
      location of these structures and their relation to the glass-phase of the
      ceramic, as well as its role in the nanomechanical anchoring of the ceramic are
      still to be clarified. The values of debonding stress were 41.67 +/- 5.01 MPa,
      52.89 +/- 8.06 MPa and 56.58 +/- 10.21 MPa for Carat, VITA VMK68 ceramic and
      Vision, respectively. These parameters do not present significant difference at p
      > or = 0.05 among the three types of ceramics. Based on our measurements it is
      highly likely that the micromorphology of interface is basically determined by
      the composition of the alloy while in the chemical composition of the newly
      developed phases the ceramic and the parameters of firing (temperature, magnitude
      of vacuum and firing time) play an important role. Values of cracking and
      morphological resemblance suggest that the superficial micromorphological and
      nanomorphological structures, acting as mechanical anchoring elements, play an
      important role in fixing the ceramic.

PMID- 14971265
TI  - [Comparative study of hand-held nickel-titanium dental instruments based on the
      shape of the prepared root canal].
AB  - The aim of this study was to compare the shaping characteristics of two hand
      instruments: the NiTi K-files and the NiTi S-files. A total of 60 extracted human
      roots were embedded in resin blocks. The roots were divided into three groups
      according to their shape: straight, apically curved and entirely curved. Each of
      the three groups was divided into two subgroups for the NiTi K-file and the NiTi
      S-file instrumentation. The files were used with a step-back technique and
      enlarged so that the master apical file was size 30, and the canals were stepped
      back to size 40. The performance of the files was assessed by the superimposition
      of projected radiographs taken in bucco-lingual and mesio-distal views before and
      after preparation. The results were analyzed statistically using of analysis of
      covariance and Duncan's multiple range test. Although canal preparation using
      NiTi K-files was quicker, there were no statistically significant differences
      between file types. The NiTi S-file removed significantly more dentine at the
      most coronal level (p < 0.05). There were minor differences between instruments
      at the apical level. Only in the proximal view of apically curved canals prepared
      with NiTi S-files was significantly more dentine removed from the convex side of
      the wall (p < 0.05). At the middle level the NiTi S-files removed more dentine
      from the concave wall in apically curved canals. Under the conditions of this
      study, preparation with NiTi K-files produced more appropriate shapes in roots
      with apically curved canals than NiTi S-files.

PMID- 14971266
TI  - [Epidemiological study of dental fear scores in several Hungarian sub
      populations].
AB  - Authors investigated the dental fear scores (DAS, DFS) and anxieties of 362
      persons from several sub-populations living in Budapest. The subjects were: 253
      females, 109 males, aged 14 to 73. Dental fear scores were rather high (DAS: 11.0
      +/- 3.6; DFS: 42.0 +/- 16.0). Age influenced the dental fear scales (DAS and DFS)
      only; sex, and marital status influenced both dental fear scales and general
      anxiety scales (one-way ANOVA). A strong correlation between DAS and DFS, and
      somewhat lower correlation between these scales and the general anxiety scales
      were also demonstrated.

PMID- 14971267
TI  - In the Clark Center, the task for Foster and Partners and MBT was no less than to
      redefine the way interdisciplinary research is done.

PMID- 14971268
TI  - Bath Spa. Bath, England.

PMID- 14971269
TI  - Measuring the strategic readiness of intangible assets.
AB  - Measuring the value of intangible assets such as company culture, knowledge
      management systems, and employees' skills is the holy grail of accounting.
      Executives know that these intangibles, being hard to imitate, are powerful
      sources of sustainable competitive advantage. If managers could measure them,
      they could manage the company's competitive position more easily and accurately.
      In one sense, the challenge is impossible. Intangible assets are unlike financial
      and physical resources in that their value depends on how well they serve the
      organizations that own them. But while this prevents an independent valuation of
      intangible assets, it also points to an altogether different approach for
      assessing their worth. In this article, the creators of the Balanced Scorecard
      draw on its tools and framework--in particular, a tool called the strategy map-
      to present a step-by-step way to determine "strategic readiness," which refers to
      the alignment of an organization's human, information, and organization capital
      with its strategy. In the method the authors describe, the firm identifies the
      processes most critical to creating and delivering its value proposition and
      determines the human, information, and organization capital the processes
      require. Some managers shy away from measuring intangible assets because they
      seem so subjective. But by using the systematic approaches set out in this
      article, companies can now measure what they want, rather than wanting only what
      they can currently measure.

PMID- 14971270
TI  - Worse than enemies. The CEO's destructive confidant.
AB  - The CEO is often the most isolated and protected employee in the organization.
      Few leaders, even veteran CEOs, can do the job without talking to someone about
      their experiences, which is why most develop a close relationship with a trusted
      colleague, a confidant to whom they can tell their thoughts and fears. In his
      work with leaders, the author has found that many CEO-confidant relationships
      function very well. The confidants keep their leaders' best interests at heart.
      They derive their gratification vicariously, through the help they provide rather
      than through any personal gain, and they are usually quite aware that a person in
      their position can potentially abuse access to the CEO's innermost secrets.
      Unfortunately, almost as many confidants will end up hurting, undermining, or
      otherwise exploiting CEOs when the executives are at their most vulnerable. These
      confidants rarely make the headlines, but behind the scenes they do enormous
      damage to the CEO and to the organization as a whole. What's more, the leader is
      often the last one to know when or how the confidant relationship became toxic.
      The author has identified three types of destructive confidants. The reflector
      mirrors the CEO, constantly reassuring him that he is the "fairest CEO of them
      all." The insulator buffers the CEO from the organization, preventing critical
      information from getting in or out. And the usurper cunningly ingratiates himself
      with the CEO in a desperate bid for power. This article explores how the CEO
      confidant relationship plays out with each type of adviser and suggests ways CEOs
      can avoid these destructive relationships.

PMID- 14971271
TI  - Getting IT right.
AB  - Modern information technology started four decades ago, yet in most major
      corporations, IT remains an expensive mess. This is partly because the relatively
      young and rapidly evolving practice of IT continues to be either grossly
      misunderstood or blindly ignored by top management. Senior managers know how to
      talk about finances because they all speak or understand the language of profit
      and loss and balance sheets. But when they allow themselves to be befuddled by IT
      discussions or bedazzled by three-letter acronyms, they shirk a critical
      responsibility. In this article, the authors say a systematic approach to
      understanding and executing IT can and should be implemented, and it should be
      organized along three interconnected principles: A Long-Term IT Renewal Plan
      Linked to Corporate Strategy. Such a plan focuses the entire IT group on the
      company's over-arching goals during a multiyear period, makes appropriate
      investments directed toward cutting costs in the near term, and generates a
      detailed blueprint for long-term systems rejuvenation and value creation. A
      Simplified, Unifying Corporate Technology Platform. Instead of relying on
      vertically oriented data silos that serve individual corporate units (HR,
      accounting, and so on), companies adopt a clean, horizontally oriented
      architecture designed to serve the whole organization. A Highly Functional,
      Performance-Oriented IT Organization. Instead of functioning as if it were
      different from the rest of the firm or as a loose confederation of tribes, the IT
      department works as a team and operates according to corporate performance
      standards. Getting IT right demands the same inspired leadership and superb
      execution that other parts of the business require. By sticking to the three
      central principles outlined in this article, companies can turn IT from a
      quagmire into a powerful weapon.

PMID- 14971272
TI  - How to have an honest conversation about your business strategy.
AB  - Too many organizations descend into underperformance because they can't confront
      the painful gap between their strategy and the reality of their capabilities,
      their behaviors, and their markets. That's because senior managers don't know how
      to engage in truthful conversations about the problems that threaten the business
      -and because lower-level managers are afraid to speak up. These factors lie
      behind many failures to implement strategy. Indeed, the dynamics in almost any
      organization are such that it's extremely difficult for senior people to hear the
      unfiltered truth from managers lower down. Beer and Eisenstat present the
      methodology they've developed for getting the truth about an organization's
      problems (and the truth is always embedded within the organization) onto the
      table in a way that allows senior management to do something useful with it. By
      assembling a task force of the most effective managers to collect data about
      strategic and organizational problems, the senior team sends a clear message that
      it is serious about uncovering the truth. Task force members present their
      findings to the senior team in the form of a discussion. This conversation needs
      to move back and forth between advocacy and inquiry; it has to be about the
      issues that matter most; it has to be collective and public; it has to allow
      employees to be honest without risking their jobs; and it has to be structured.
      This direct feedback from a handful of their best people moves senior teams to
      make changes they otherwise might not have. Senior teams that have engaged in
      this process have made dramatic changes in how their businesses are organized and
      managed--and in their bottom-line results. Success that begins with honest
      conversations begets future conversations that further improve performance.

PMID- 14971273
TI  - Launching a world-class joint venture.
AB  - More than 5,000 joint ventures, and many more contractual alliances, have been
      launched worldwide in the past five years. Companies are realizing that JVs and
      alliances can be lucrative vehicles for developing new products, moving into new
      markets, and increasing revenues. The problem is, the success rate for JVs and
      alliances is on a par with that for mergers and acquisitions--which is to say not
      very good. The authors, all McKinsey consultants, argue that JV success remains
      elusive for most companies because they don't pay enough attention to launch
      planning and execution. Most companies are highly disciplined about integrating
      the companies they target through M&A, but they rarely commit sufficient
      resources to launching similarly sized joint ventures or alliances. As a result,
      the parent companies experience strategic conflicts, governance gridlock, and
      missed operational synergies. Often, they walk away from the deal. The launch
      phase begins with the parent companies' signing of a memorandum of understanding
      and continues through the first 100 days of the JV or alliance's operation.
      During this period, it's critical for the parents to convene a team dedicated to
      exposing inherent tensions early. Specifically, the launch team must tackle four
      basic challenges. First, build and maintain strategic alignment across the
      separate corporate entities, each of which has its own goals, market pressures,
      and shareholders. Second, create a shared governance system for the two parent
      companies. Third, manage the economic interdependencies between the corporate
      parents and the JV. And fourth, build a cohesive, high-performing organization
      (the JV or alliance)--not a simple task, since most managers come from, will want
      to return to, and may even hold simultaneous positions in the parent companies.
      Using real-world examples, the authors offer their suggestions for meeting these
      challenges.

PMID- 14971274
TI  - Success that lasts.
AB  - Pursuing success can feel like shooting in a landscape of moving targets: Every
      time you hit one, five more pop up from another direction. We are under constant
      pressure to do more, get more, be more. But is that really what success is all
      about? Laura Nash and Howard Stevenson interviewed and surveyed hundreds of
      professionals to study the assumptions behind the idea of success. They then
      built a practical framework for a new way of thinking about success--a way that
      leads to personal and professional fulfillment instead of feelings of anxiety and
      stress. The authors' research uncovered four irreducible components of success:
      happiness (feelings of pleasure or contentment about your life); achievement
      (accomplishments that compare favorably against similar goals others have strived
      for); significance (the sense that you've made a positive impact on people you
      care about); and legacy (a way to establish your values or accomplishments so as
      to help others find future success). Unless you hit on all four categories with
      regularity, any one win will fail to satisfy. People who achieve lasting success,
      the authors learned, tend to rely on a kaleidoscope strategy to structure their
      aspirations and activities. This article explains how to build your own
      kaleidoscope framework. The process can help you determine which tasks you should
      undertake to fulfill the different components of success and uncover areas where
      there are holes. It can also help you make better choices about what you spend
      your time on and the level of energy you put into each activity. According to
      Nash and Stevenson, successful people who experience real satisfaction achieve it
      through the deliberate imposition of limits. Cultivating your sense of "just
      enough" can help you set reachable goals, tally up more true wins, and enjoy
      lasting success.

PMID- 14971275
TI  - Turning gadflies into allies.
AB  - Multinational companies are the driving force behind globalization, but they are
      also the source of many of its most painful consequences, including currency
      crises, cross-border pollution, and overfishing. These problems remain unsolved
      because they are beyond the scope of individual governments; transnational
      organizations have also proved unequal to the task. Nonprofit, nongovernmental
      organizations have leaped into the breach. To force policy changes, they have
      seized on all forms of modern persuasion to influence public sentiment toward
      global traders, manufacturers, and investors. By partnering with NGOs instead of
      opposing them, companies can avoid costly conflict and can use NGOs' assets to
      gain competitive advantage. So far, however, most companies have proved ill
      equipped to deal with NGOs. Large companies know how to compete on the basis of
      product attributes and price. But NGO attacks focus on production methods and
      their spillover effects, which are often noneconomic. Similarly, NGOs are able to
      convert companies' standard competitive strengths--such as size and wide market
      awareness of their brands--into liabilities. That's because the wealthier and
      better known a company is, the juicier the target it makes. Emboldened by their
      successes, NGOs continue to take on new causes. By partnering with NGOs instead
      of reflexively opposing them, companies could draw on NGOs' key strengths-
      legitimacy, awareness of social forces, distinct networks, and specialized
      technical expertise--which most companies could use more of. And with NGOs as
      allies and guides, companies should also be able to accelerate innovation,
      foresee shifts in demand, shape legislation affecting them, and, in effect, set
      technical and regulatory standards for their industries.

PMID- 14971277
TI  - [Up-date on parotid gland surgery].

PMID- 14971276
TI  - Enhanced surveillance of invasive meningococcal disease in Canada: 1 January,
      1999, through 31 December, 2001.

PMID- 14971278
TI  - [Current indications for surgical treatment of asymptomatic primary
      hyperparathyroidism].
AB  - The clinical picture of hyperparathyroidism has gone toward deep modifications in
      the last few decades, and currently this disease is more frequently asymptomatic.
      So, the question is raising concerning which patients have to be operated, due to
      the substantial benignity of the disease and the lack of well defined symptoms.
      Classical indications for surgery have been formulated more than a decade ago and
      are as follows: calcemia higher than 3 mmol/L, previous episode of life
      threatening hypercalcaemia, reduced creatinine clearance, nephrolithiasis,
      hypercalciuria, osteoporosis. In the last years other indications have been
      added, on the basis of clinical and epidemiological studies that have contributed
      to broaden our knowledgement on the evolution and compliances of the disease.
      Among these, the following data have to been kept in mind: history of previous
      atraumatic fractures, vertebral osteopenia (Z-score < -2), vitamin D deficiency,
      perimenopausal status, neuromuscular or psychical disturbances.

PMID- 14971279
TI  - Noninvasive parathyroid imaging in primary hyperparathyroidism.
AB  - Several studies suggested that preoperative localization of abnormal parathyroid
      (PT) glands may be useful in reducing operative time facilitating
      parathyroidectomy, especially in patients with ectopic PT glands. At present,
      noninvasive techniques used to evaluate patients with primary HPT include (1)
      99mTc-sestamibi scintigraphy, (2) high-resolution neck ultrasonography, (3) CT
      scanning, and (4) magnetic resonance imaging (MRI). The sensitivity and positive
      predictive value of each technique range from 70% to 90%, and a combination of
      two of more tests may significantly improve the results. In the minimally
      invasive era both radioguided and video-assisted parathyroidectomy require an
      accurate preoperative localization of the abnormal PT glands, and PT imaging
      should be obtained before surgery in all patients with primary
      hyperparathyroidism, with the aim of reducing operative time and hospital stay.

PMID- 14971280
TI  - The actual role of classic bilateral cervicotomic approach for primary
      hyperparathyroidism in the era of minimally invasive surgery.
AB  - Recent advances in preoperative localisation of parathyroid adenomas and
      intraoperative prove of complete removal of hyperfunctioning parathyroid tissue
      have fostered less invasive operative procedures which directly target the
      diseased gland. Such strategies have partially replaced the previous gold
      standard procedure of bilateral neck exploration. We herein report on our own
      series of 1099 consecutive operations for primary hyperparathyroidism performed
      in a 16 year period and provide information and arguments for primary bilateral
      exploration in selected cases. 97.1% of patients were cured by the primary
      operation. From 1999 through 2001, 200 patients underwent bilateral neck
      exploration, whereas 63 unilateral operations were performed (33 patients were
      treated by minimally invasive video-assisted parathyroidectomy (MIVAP) and 30 by
      minimally invasive open parathyroidectomy (MIOP). In the remaining 200 patients
      minimally invasive unilateral parathyroid surgery was not feasible due to
      concomitant goiter (n = 102), lack of preoperative localisation (n = 30),
      previous thyroid surgery (n = 10), suspected multiglandular disease (n = 10), or
      other reasons (n = 8). In 40 patients the decision for bilateral neck exploration
      was made despite feasibility of a unilateral approach. CONCLUSION: Whereas
      unilateral exploration produced excellent cure rates in older patients, it is not
      recommended in patients with a high likelihood of multiglandular disease,
      presence of a large or multinodular goitre, high PTH levels, giant adenoma,
      unclear MIBI scans or an unreliable OPTH assay. Contrasting recent reports on a
      dramatic shift of technique towards minimally invasive procedures unilateral
      parathyroid surgery may not be preferably advisable in a majority of patients
      from countries with insufficient iodine supplementation.

PMID- 14971281
TI  - The role of intraoperative quick PTH measurements in primary hyperparathyroidism.
AB  - BACKGROUND: In patients with primary hyperparathyroidism (PHPT), circulating
      concentrations of intact parathyroid hormone (PTH), decline dramatically within
      minutes following surgical excision of hyperfunctioning parathyroid tissue. The
      magnitude of this decay correlates with the completeness of resection of
      hyperfunctioning parathyroid tissue and can be monitored during the operation.
      METHOD: Intraoperative Quick PTH (QPTH) monitoring and pitfalls of more than 350
      patients, who were operated because of primary hyperparathyroidism are analyzed.
      Special attention is given to correct baseline values and interpretation of QPTH
      values. RESULTS: QPTH monitoring is able to distinguish reliably between single
      and multiple gland disease and is an indispensable prerequisite for any form of
      limited parathyroid exploration. Experience with QPTH monitoring is necessary to
      achieve the excellent results known from bilateral neck exploration. CONCLUSION:
      Applying correct baseline values and cautious interpretation of QPTH values
      results in excellent results. Nevertheless more data must be collected to allow
      reliable interpretation of QPTH monitoring in all patients with PHPT.

PMID- 14971282
TI  - [Video-assisted minimally invasive parathyroidectomy with lateral approach in
      patients with primary hyperparathyroidism].
AB  - INTRODUCTION: Different minimally invasive techniques of parathyroidectomy have
      been described. We performed a retrospective study to evaluate the indications
      and results of video-assisted parathyroidectomy (VAP) in the management of
      patients with primary hyperparathyroidism (PHPT). MATERIALS AND METHODS: Between
      1998 and 2002, 528 patients were operated on because PHPT. VAP was proposed for
      patients with sporadic PHPT, without associated goiter and previous neck surgery,
      in whom a single adenoma was localized. VAP was performed by lateral approach
      with insufflation for patients with adenoma located deeply in the neck and by
      gasless midline approach for anteriorly located adenomas. A quick parathyroid
      (qPTH) assay was used during the surgical procedure. Calcemia, phosphoremia and
      PTH were systematically evaluated after surgery. RESULT: Of 528 patients with
      PHPT, 228 (43%) were not eligible for VAP because associated nodular goiter (99
      cases), previous neck surgery (42 cases), suspicion of multiglandular disease (25
      cases), lack of preoperative localization (48 cases), and miscellaneous causes
      (14 cases). VAP was performed in 300 patients with sporadic PHPT: 282 lateral
      access, 17 midline access and one thoracoscopy. Mean operative time was 50'.
      Conversion to conventional parathyroidectomy was required in 14% of cases. One
      patient presented a definitive recurrent nerve palsy. One persistent and one
      recurrent PHPT were observed. CONCLUSION: VAP can be proposed for patients with
      PHPT. Immediate results of VAP are similar to those obtained with conventional
      parathyroidectomy; no conclusions can be drawn in terms of influence of VAP on
      the outcome of the patients operated for PHPT.

PMID- 14971283
TI  - [Video-assisted minimally invasive parathyroidectomy with median access.
      Technical changes: case load 1999-2002].
AB  - INTRODUCTION: In 1997 a Minimally Invasive Video Assisted Technique for
      Parathyroidectomy (MIVAP) was developed in the University of Pisa. In this review
      we examine the last three years of MIVAP (240 cases) in order to identify the
      advantages and the limits of the procedure after the first-period development of
      the technique. RESULTS: In our experience, 65% of patients affected by primary
      hyperparathyroidism (PHPT) turned out to be eligible for MIVAP. During the first
      years several selection criteria were strictly followed; more recently, some
      initially absolute contraindications to the operation have been interpreted more
      flexibly. Mean operative time is 35 minutes. 18 conversions (7.5%) to traditional
      open cervicotomy were needed and in 4 cases (1.6%) no affected parathyroid tissue
      was removed. CONCLUSIONS: At present, we consider absolutely necessary for MIVAP:
      preoperative localization of an adenoma with at least one imaging study (US or
      MIBI scintiscan) and the availability of QPTH intraoperative assay. No absolute
      contraindications other than the size of the lesions and the suspect of
      parthyroid carcinoma are identified for patients with PHPT. Moreover, MIVAP has
      proved to have further advantages when compared to other mini invasive procedures
      such as the demonstrated possibility to perform a traditional bilateral
      exploration, when indicated. Nevertheless, a great degree of experience is
      requested for this procedure. In conclusion, MIVAP permits to significantly
      reduce postoperative pain, size of the incision, days of hospitalisation and,
      finally, the cost of the entire procedure without affecting in any way the
      success rate of the traditional operation and without an increase of the
      complications.

PMID- 14971284
TI  - Minimally invasive radioguided parathyroidectomy.
AB  - In the last years, with the aim of reducing operative time and having better
      cosmetic results, minimally-invasive parathyroidectomy (MIP) has become to be
      extensively performed. Several techniques are available, including video
      endoscopic techniques, and radioguided parathyroidectomy. In patients undergoing
      radio-guided parathyroidectomy receive an intravenous injection of 99mTc
      sestamibi 60-90 minutes before the operation was scheduled to start. Four early
      images are obtained 5 minutes after radiopharmaeutical administration, with the
      aim of confirming the side and site of the enlarged PT gland. Intraoperative
      nuclear mapping using a hand-held gamma probe and quantitative gamma camera
      counting in the four quadrants is obtained. A 2-3 cm incision is made, and the
      enlarged PT gland excision is guided by the probe, resulting in a decline in
      radioactivity in the corresponding quadrant. Intraoperative quick PTH is
      routinely assayed. When the PTH levels at 10 min fail to fall to less than 50% of
      the preoperative levels, a multiglandular disease should be suspected and a
      bilateral neck exploration is usually required. MIP is a safe, cost-effective
      alternative to bilateral exploration, and should be considered the procedure of
      choice in patients with primary HPT, when preoperative imaging tests have
      suggested the presence of a PT adenoma. Radioguided MIP may improve the success
      rate of surgery in patients with primary hyperparathyroidism.

PMID- 14971285
TI  - [Surgical treatment of primary hyperparathyroidism during MEN1 and other
      genetically determined forms].
AB  - In MEN1, HPT manifests precociously and it is almost constant. Whereas in MEN2 it
      seldom occurs and has been reported in 17 to 40% of the cases, in MEN1 HPT is
      much more severe, amplifying the secretion of associated gastrinomas. In MEN1,
      multiglandular involvement is almost constant, and in case of less than subtotal
      parathyroidectomy, recurrence rate varies from 20 to 40%. Practically, HPT is the
      first worry of the surgeon in a MEN1 setting, and the last in a MEN2 setting. It
      is rather important to think to the potential hypoparathyrodism at the time of
      the cervicotomy for MTC. The operative strategy is to examine all parathyroid
      glands. In MEN1, it is necessary to be aggressive and perform a subtotal
      parathyroidectomy, regardless of gland gross appearance. In the MEN2 only the
      enlarged glands should be removed. In both setting a bilateral cervical
      thymectomy should be done for removal of a possible supernumerary gland.

PMID- 14971286
TI  - Persistent or recurrent primary hyperparathyroidism.
AB  - More than 95% of patients with Primary Hyperparathyroidism (PHPT) are treated
      successfully at the initial operation when the operation is done by an
      experienced surgeon, but the success rate is considerably lower when done by an
      unexperienced surgeon. The approach to patients with persistent and recurrent
      PHPT is to confirm the diagnosis and to use precise localization procedures done
      by expert radiologists. Reexploration after one or more previously failed
      parathyroid operations is unfortunately associated with a higher morbidity and a
      lower success rate. Improved pre- and intraoperative testing during the last
      decade has improved the results of reoperation and allowed more focused
      approaches. Preoperatively, we recommend a combination of sestamibi scanning,
      ultrasound, and MRI scanning. Highly selective venous sampling for iPTH is
      recommended for patients with recurrent or persistent PHPT when the non-invasive
      studies are negative, equivocal, or discordant. Several factors such as age of
      the patient, severity of symptoms, comorbidity, and the results of localization
      studies, should all be considered in the management of these patients although we
      believe that reoperation is indicated for most of these patients. Today
      successful reoperations can be done in more than 90% of patients with a
      relatively low morbidity rate.

PMID- 14971287
TI  - [Surgical treatment of secondary and tertiary hyperparathyroidism].
AB  - AIMS: To determine whether, in secondary and tertiary hyperparathyroidism (HPT),
      quick parathyroid hormone (PTH) assay can be used to prevent persistent or
      recurrent HPT. Another point was to determine, considering the PTH decrease, the
      cut-off point at which the operation could be considered well performed. METHODS:
      A retrospective study was performed evaluating all cases operated on since 1975
      until 2002, 679 patients, and particularly the analysis of two groups of patients
      that underwent surgical treatment for secondary and tertiary HPT in the period
      1995-2002. In the first group, (January 1995-October 1999) 207 (167 HPT II and 40
      HPT III) neck explorations were performed without the aid of quick PTH assay; in
      the second group (November 1999-December 2002), 192 (153 HPT II and 39 HPT III)
      patients were operated on with blood samples for quick PTH. RESULTS: In the first
      group the percentage of success for secondary HPT was 93.8 versus 96.2 of the
      second group and 91.7 versus 94.2 for tertiary HPT. In reoperations the
      percentage of success was 72.7 in the first group and 87.5 in the second one.
      CONCLUSIONS: There are no substantial differences in persistences or recurrences
      between subtotal or total parathyroidectomy (PTx) with autotransplantation (AT).
      The choice of the gland to be left in the neck or transplanted in the forearm and
      the modalities of doing so are very important, considering the macroscopical and
      histological aspects. Intraoperative PTH monitoring is a useful aid during the
      first cervical exploration for secondary and tertiary HPT to prevent the
      development of persistent or recurrent HPT. The cut-off point for secondary HPT
      is 70% (in difficult cases with more than 2 assays, 75%) and for tertiary HPT 50%
      and 70% respectively.

PMID- 14971288
TI  - [Conservative... and non conservative... treatment of renal blunt injuries].
AB  - Whether patients with blunt renal trauma should be managed conservatively without
      surgery or undergo surgery is often hard to decide. We describe three clinical
      cases of blunt renal trauma, all involving the left kidney. All three patients
      had abdominal ultrasound studies and computerized tomographic (CT) scans. In the
      first case, an accidental fall led to severe injury of the renal hilus causing
      massive retroperitoneal extravasation. The patient underwent emergency
      nephrectomy and survived. The second case concerned a patient who was involved in
      a road accident, suffered injuries mainly affecting the spleen, and underwent
      splenectomy. A postoperative CT scan showed left renal vein thrombosis
      functionally excluding the inferior pole of the kidney. The patient received
      conservative non surgical treatment. A follow-up imaging study showed that
      although the thrombosis had resolved the renal pole had failed to regain normal
      function. In the third case, mild apparently unimportant trauma led to a massive
      hemorrhage responsible for a severe shock state. Despite prompt nephrectomy,
      renal failure and and pulmonary complications developed and one month after the
      injuries the patient died. The medical history referred to a "chronic hematoma"
      secondary to a childhood injury. In this case, the pre-existing hematoma probably
      led to a permanent communication with the vascular and excretory tree thus
      resulting in a kind of "silent" fistula that the relatively mild injury
      unexpectedly disrupted. For the two left nephrectomies we used a midline approach
      after isolating the renal Treitz vessels; special care was taken to mobilize the
      left colon. Although blunt renal trauma often responds to non surgical
      conservative treatment, some patients should undergo prompt surgery. All patients
      must be scheduled for long-term clinical and imaging follow-up.

PMID- 14971289
TI  - [Conservative treatment of chronic obstructive arterial disease with iloprost and
      physical training: assessment of results in 5 years of a study with 360
      patients].
AB  - INTRODUCTION: The treatment of patients with Peripheral Arterial Occlusive
      Disease (P.A.O.D.) is, until now, a therapeutics challenge. The purpose of this
      study was to confirm the safety of Iloprost infusion, to estimate the results
      after an Home Exercise Program joined to the therapy and to identify groups of
      patients with P.A.O.D. that can benefit from Iloprost therapy. MATERIAL AND
      METHODS: 360 patients with and without diabetic with P.A.O.D. (Peripheral
      Arterial Occlusive Disease) at the stage of II, III, & IV, with Buerger Syndrome,
      were treated with Iloprost at the maximum dosage: 2 ng/kg/min for 6 hours a day,
      for a minimum of 1 week and a maximum of 3 weeks with cycles of therapy every 3,
      6 or 12 months. At the end of each cycle of therapy there was assigned an Home
      Exercise Program. Patients with symptoms of pain are observed in the study and
      monitored for how long the pain lasted or diminished. The clinical benefit was
      evaluated on the reduction of the pain and analgesics, on the improvement of the
      trophics lesions and on the increase of gait's distance. RESULTS: After 5 years
      of follow up, it was reported 12.2% of major amputations and 3.6% of deads. Over
      60% of the patients, that were at risk for amputation at the beginning of the
      study, were alive. The tolerability of therapy was been very acceptable.
      CONCLUSIONS: This study, at the end of 5 years, showed that the therapeutic
      infusion of Iloprost associated with an intensive Home Exercise Program, can,
      before 12 months, show patient improvement of the gait's distance from 50-200%.

PMID- 14971290
TI  - [Non-neoplastic intestinal occlusion].
AB  - In the last ten years etiology's frequency of non-neoblastic bowel occlusions has
      changed. Headway against occlusions percentage decreasing due to post-operative
      stenosis, hernial strangulation, adhesional bridles, etc., mechanical ileus
      observations increase in percentage round about 20%, as colon acquired
      diverticulitis complications. This is essentially due to the mean survival
      increasing in the whole occidental world and, particularly, in Italy. Therefore,
      we have to expect an increase of this kind of occlusion that presents, for his
      characteristics, a moderate diagnostic etiological pre- and intra-operative
      difficulty. This diagnostic doubt can afford a destroyer intervention, with a
      useless lymphadenectomy, more than needful with morbidity and mortality
      increasing.

PMID- 14971291
TI  - Analogic evaluation of pain during inguinal hernioplasty under local anaesthesia.
AB  - OBJECTIVE: The authors evaluate intraoperative pain in patients undergoing
      tension-free inguinal hernioplasty under local anaesthesia. MATERIAL AND METHODS:
      One hundred and fourteen primary inguinal hernia repairs were carried out at the
      Department of General Surgery I of Catania University Polyclinic from January to
      September 2002. 2% Mepivacaine cloridrate was the local anesthetic of choice.
      Intraoperative pain was measured by a visual analog scale. RESULTS: A mean
      analogic score of 1.9 (range 0-2.9) was obtained. Intraoperative complications
      were recorded only in 2 patients (1.7%). There was no operative mortality. All
      patients were up and about straightaway after surgery, had a light meal two hours
      later and were discharged within one day of operation. CONCLUSIONS: Inguinal
      hernia repair under local anaesthesia is well tolerated and is associated with a
      low risk of complications.

PMID- 14971292
TI  - [Critical update on the no-touch technique in colonic cancer using the grasping
      tie].
AB  - The time honoured strategy of "no-touch" in the surgery of colon cancer does not
      stand an anatomical and patho-physiological criticism, also on the basis of some
      results of the literature. The personal experience of the problem leads to the
      proposal of an alternative realization of the procedure, that is an up-to-date of
      the classic method, and is really worth and easy to be overall adopted. The
      suggestion is to seal bipolarly the colon tract with the tumour by mean of the
      original grasping tie from the very beginning of the operation, and then to
      temporarily clamp the mesocolon close to the gut, before going on with the
      surgical dissection, lymphectomy and exeresis as usual. This procedure is able to
      completely isolate from the first steps of the operation the affected tract of
      the colon, so opposing the possible spreading of tumour cells in the portal and
      in the systemic venous stream during the following surgical manipulations. The
      rationale of the proposal is that of a more efficacy of the "no-touch" strategy
      based on strict anatomical and patho-physiological considerations.

PMID- 14971293
TI  - [Gastric antral vascular ectasia (GAVE) or watermelon stomach syndrome: report of
      3 cases and clinical and therapeutic indications].
AB  - OBJECTIVE: The authors report their experience in diagnosis, treatment and
      ambulatorial follow up of 3 cases of obscure upper gastrointestinal bleeding by
      gastric antral vascular ectasia (GAVE). EXPERIMENTAL DESIGN: Complete clinical
      report of 3 cases. Clinical and endoscopic indication, evaluation of
      effectiveness of endoscopic treatment with bipolar electrocoagulation and follow
      up. SETTING: Operative Unit of General and Thoracic Surgery. University "Paolo
      Giaccone" of Palermo. INTERVENTION: Endoscopic treatment by multiple session with
      bipolar electrocoagulation. No complications were registered. RESULTS: Complete
      recovery with "restitutio ad integrum". No relapse were recorded at follow up.
      CONCLUSIONS: The objective of the treatment is to recognize the site of obscure
      bleeding and then stop it. The choice between pharmacological, endoscopic and
      surgical treatment is individual for each patient. According to us, the
      endoscopic treatment is the first step in a gradual clinical approach, to detect
      the site of the lesion, to treat with bipolar electrocoagulation or with Argon
      Plasma Coagulator (lower wall penetration and minimal risk of perforation).

PMID- 14971294
TI  - [Toxicologic analysis of some adrenergic-beta blockers in the diagnosis of
      intoxications].
AB  - The study aimed at finding effective techniques of qualitative and quantitative
      analysis of selected beta-adrenergic blockers, useful both for monitoring of
      therapy and for thanatological diagnosis of intoxications. The studies took
      advantage of gas chromatography (GLC) and high performance liquid chromatography
      (HPLC). For isolation of studied compounds from biological material, classical
      and solid phase extraction procedures (SPE) Extrelut-20 (Merck), Abselut Nexus
      (Varian), STRATA C--18 E (Phenomenex) were used. The program included the
      analysis of most frequently applied derivatives: Acebutolol, Atenolol,
      Bunitrolol, Bupranolol, Labetolol, Metipranolol, Metoprolol, Oxprenolol,
      Practolol, Propranolol.

PMID- 14971295
TI  - [Male and female suicides in the material of Department of Forensic Medicine in
      Krakow--comparative analysis].
AB  - The study presents the results of research into completed suicide obtained by
      cooperation between the Department of Forensic Medicine and the University
      Psychiatry Department in Krakow. The aim of the research is to determine
      similarities and differences among the cases of completed suicide depending on
      the sex of the subjects. The authors analyzed cases of completed suicide
      committed in Krakow and its environs in the years 1991-2000. The groups of
      females and males have been compared from the point of view of medical-forensic
      and psychosocial aspects. The authors also present a sketch of the bibliography
      regarding the topic, and the comparison between the results of the present study
      and the results of earlier studies from Krakow environs on the phenomenon of
      suicide.

PMID- 14971296
TI  - [Evolution of Patient's Rights in Polish legislation in the years 1918-1998 in
      comparison to the European Community Norms].
AB  - The evolution of patient's rights covering the years of 1918-1998 in Polish
      legislation is presented. These rights have been discussed within the group of
      law acts pertaining to medical practice and to health care institutions. The
      patient's rights included in the European Council's documents have also been
      considered.

PMID- 14971297
TI  - [Myocardial infarction as a work accident in Polish Supreme Court decisions. Part
      I. Excessive stress at work].
AB  - This paper deals with Polish Supreme Court opinions on the acceptance of
      myocardial infarction as work accident. From them the principle emerges that
      excessive physical or mental work stress can be accepted as the external cause of
      myocardial infarction in an employee, whereby the excess strain should be judged
      in each case individually and with reference to the individual situation.

PMID- 14971298
TI  - [Myocardial infarction as a work accident in Polish Supreme Court decisions. Part
      II. Job contraindications due to an employee's state of health].
AB  - This paper presents the second part on opinions given by the Polish Supreme Court
      on the acceptance of myocardial infarction as work accident. This it can be seen
      that, in certain cases, the judgements of the Court are contradictory. For in
      some cases, an external cause is recognized in the act of permitting employees to
      work whose state of health would contraindicate the performance of their duties,
      while in others, the principle is accepted that work duties not considered
      harmful for healthy people cannot be deemed an external cause for people with
      health problems. An external cause according to the Supreme Court may also be the
      act of allowing an employee to work without a valid medical examination, or even
      by not conducting routine required work-related medical examinations on time.

PMID- 14971299
TI  - [Some issues concerning the use of firearms with Flobert cartridges].
AB  - The aim of the work is to analyze and evaluate legal, criminalistic and
      criminological problematic issues appearing in Lithuania due to circulation of
      firearms designed for the Flobert cartridge. The purpose of guns with the Flobert
      cartridge is shooting training in closed areas. Provided the kinetic energy of
      Flobert cartridge is not bigger that 7.5 J. the guns meant for those bullets have
      been classified to unlimited circulation of guns since 1999 in Lithuania. Now
      these firearms can be purchased by anyone over 18. Due to this reason the demand
      for these firearms has increased. The sale of these firearms amounts to several
      thousands (the population of Lithuania is more than 3.5 million). The analyses of
      the authors show that these firearms are not used in accordance with their
      purpose. Experimental practice and experimental research proved that these
      firearms can cause serious bodily injuries. The latter fact allowed the authors
      to formulate propositions regarding legal regulation of circulation of these
      firearms.

PMID- 14971300
TI  - [Suicidal single intraoral shooting by a shotgun--risk of misinterpretation at
      the crime scene].
AB  - The authors presented two cases of suicidal single intraoral shooting by a
      shotgun. The first case relates to a victim found near the peak of Swinica in the
      Tatra mountains. When the circumstances could have suggested fatal fall from a
      height and minute, insignificant external injuries were found, the pistol found
      at the scene has been the most important indicator leading to the actual cause of
      death. The second case relates to a 38-year-old male found in this family house
      in a village. Severe internal cranial injury (bone fragmentation) was diagnosed
      at the scene. A self-made weapon was previously removed and hidden from the scene
      by a relative of the victim. Before regular forensic autopsy X-ray examination
      was conducted which revealed multiple intracranial foreign bodies of a shape of a
      shot. After the results of the autopsy the relative of the deceased indicated the
      location of the weapon.

PMID- 14971301
TI  - [Sudden cardiac death of a young male due to fibromuscular dysplasia of the left
      coronary artery].
AB  - Arteriosclerosis and its complications are the most frequent cause of death due
      to cardiovascular diseases. Other different, considerably rare arterial changes
      can lead to a fatal result as well. The authors presented a case of a 31-year-old
      male. Postmortem examination revealed a narrowed lumen and thrombosis of the left
      coronary artery due to fibromuscular dysplasia and scarification of the
      myocardium. Hemodynamic disturbances due to left ventricular failure lead to the
      death of the young adult.

PMID- 14971302
TI  - [Retinal hemorrhages as a case for shaking trauma. Case report].
AB  - An interesting shaking trauma case was reported. A detailed analysis of the
      pattern of injuries and their progress allowed to reconstruct the mechanism and
      time point of cerebral lesions in a 6 week old infant who survived the impact.
      The necessity of postmortem investigation of the fundus and cranial nerves in
      fatal cases of shaking trauma is stressed.

PMID- 14971303
TI  - [Controversies concerning the comma. The voice in the discussion].
AB  - In the article, a case is presented, which was assessed in accordance with the
      Constitutional Tribunal sentence of July 7th, 2003. Due to an essential change in
      the legal system entailing a return to the contents of art. 156 section 1 p. 2 of
      the Penal Code resolved on June 6th, 1997, this sentence caused the forming of
      the opinions which are medically illogical and contradictory to medico-legal
      experience.

PMID- 14971304
TI  - [Conference report of American Association of Automotive Medicine (AAAM) and
      International Research Committee of Biokinetics (IRCOBI) and IRCOBI, Lizbona,
      Sept. 22-26, and Warsaw, October 13-14, 2003].

PMID- 14971305
TI  - The positive way of thinking and the acquaporines.

PMID- 14971306
TI  - Optimization of the RP-HPLC method for multicomponent analgetic drug
      determination.
AB  - The optimization of RP-HPLC method defined the simultaneous influence of some
      important conditions, such as the mobile phase composition, pH of the mobile
      phase and temperature, on the separation and determination. The RP-HPLC method
      was done for the determination of paracetamol, caffeine and propyphenazone in a
      multicomponent pharmaceutical dosage form. The separation factor values define
      the optimal conditions, which were confirmed by analysing the appropriate
      mathematical models. The chromatographic system Hewlett Packard 1100 consisted of
      a HP 1100 pump, HP 1100 UV-VIS detector and HP integrator. Separations were
      performed on a Beckman Ultrasphere ODS 4.6 x 150 mm, 5 microns particle size
      column. Samples were introduced through a Rheodyne injector valve with a 20
      microL sample loop. UV detection was performed at 265 nm and phenobarottons was
      used as an internal standard. The optimization was performed within the pH range
      from 2.5 to 6.0; temperature range from 20 degrees C to 55 degrees C and
      composition of the mobile phase methanol-water from (30:70 V/V) to (65:35 V/V).
      The three-D graphs, constructed with sixty-four experimental points, confirmed
      the optimal conditions for the determination of the investigated analgetic drugs.

PMID- 14971307
TI  - Study of glimepiride-b-cyclodextrin complex.
AB  - The interaction of glimepiride with b-cyclodextrin (b-CD) has been studied by
      several analytical techniques, including 1H NMR, infrared spectroscopy (FTIR),
      powder x-ray diffractometry (XRD), thermal analysis (DSC) and scanning electron
      microscopy (SEM). The existence of an inclusion complex was proved in solution by
      phase solubility techniques and 1H NMR, and in the solid state by DSC, FTIR and
      XRD, being isolated by sealed heating and freeze drying procedures.

PMID- 14971308
TI  - Pyrimidines. Part II: Synthesis of novel pyrimidines, 1,2,4-triazolo[4,3
      a]pyrimidin-7-ones and pyrimidino[2,1-c][1,2,4]triazin-8-ones for their
      antimicrobial and anticancer activities.
AB  - Five main classes of novel pyrimidine derivatives have been synthesized; namely 6
      substituted phenyl-5-cyano-3-methyl-2-phenacylhydrazino-3,4-dihydropyrimidin-4
      ones 4a-e; 6-substituted phenyl-2-arylidene hydra-zino-5-cyano-3-methyl-3,4
      dihydropyrimidin-4-ones 5a-i; 6-substituted phenyl-2-acylhydrazino-5-cyano-3
      methyl-3,4-dihydropyrimidin-4-ones 7a-d, 8a-e and 9a-c; three novel series of
      1,2,4-triazolo[4,3-a] pyrimidones 10a,b, 11a-d and 12a-d and 6-substituted phenyl
      7-cyano-9-methyl-3-phenyl or 4-chlorophenyl-4,9-dihydropyrimido[2,1-c][1,2,4]
      triazin-8-ones 13a-c. Besides, the azide compound 2-azido-5-cyano-3-methyl-6
      phenyl-3,4-dihydropyrimidin-4-one 6 was also synthesized. The prepared compounds
      were tested for antimicrobial and anticancer activity. Compounds 4b and 4d showed
      promising activity against Escherichia coli. Compounds 3c, 5c, 5e, 5g and 7b were
      active in the three cell line antitumor one dose primary assay and were evaluated
      in the 60 human tumor full panel cell line invitro screening. Compound 5c showed
      promising activity against all types of leukemia especially leukemia K-562 and
      leukemia SR with GI50 = 1.61 and 2.63 mmol/l respectively.

PMID- 14971309
TI  - Synthesis of some new thiazole derivatives of pharmaceutical interest.
AB  - Reaction of 4-amino-3-phenyl-5-ethoxycarbonyl-thiazole-2-thione with
      phenylisothiocyanate gave (2) which when boiled with acetic acid gave (3).
      Treatment of (2) with monochloroacetic acid resulted in the formation of
      thiazolidinone derivative (4). Reaction of (2) with malonic acid gave (5).
      Condensation of (1) with aromatic aldehydes afforded Schiffe base derivatives
      (6a,b). Treatment of (1) with malononitrile, ethyl cyanoacetate and acetonitrile
      resulted the formation of pyridine derivatives (7a,b,c). The reaction of (1) with
      urea and thiourea gave compound (8). Condensation of (1) with o-phenylenediamine
      and o-aminophenol gave compound (9). Reaction of (1) with nitrous acid followed
      by coupling with ethylacetoacetate afforded (10). Bromination of (10) gave bromo
      derivative (11). The structures of the hitherto unknown compounds have been
      confirmed by analytical and spectral methods. The newly synthesized compounds
      were screened for antibacterial activity.

PMID- 14971310
TI  - Purification and some properties of African oil bean seed lipoxygenase--Part 1.
AB  - Lipoxygenase was extracted from African oil bean seed and purified by ammonium
      sulphate precipitation, gel filtration on Sephadex G-25 and ion-exchange
      chromatography on DEAE--cellulose column. The enzyme was purified 79.63 fold and
      36% of the enzyme activity was recovered. The molecular weight of the enzyme was
      102,000 daltons and the peroxide value was 10.56 x 10(-3) mM. The Vmax was 0.14
      OD min-1 while the Km value was 1.92 x 10(-4) M. The enzyme had an optimum pH of
      7.0 and optimum temperature of 30 degrees C. While diethyl-dithiocarbamate was
      the best inhibitor of the enzyme's oxidation of linoleic acid,
      nordihydroguiaretic acid was the best antioxidant for its oxidation of the fatty
      acid. African oil bean seed lipoxygenase had high enzyme activity of 86% when
      compared to soybean lipoxygenase (considered to be the best source of the
      enzyme). This means that African oil bean seed is a good source of lipoxygenase
      for biotechnology such as the bleaching of browned yam tubers.

PMID- 14971311
TI  - Synthesis and evaluation of in vitro antimycobacterial activity of some 5-(5
      nitro-2-thienyl)-2-(piperazinyl, piperidinyl and morpholinyl)-1,3,4-thiadiazole
      derivatives.
AB  - A new series of 5-(5-nitro-2-thienyl)-2-(piperazinyl, piperidinyl and
      morpholinyl)-1,3,4-thiadiazole derivatives(5a-g) have been synthesized and
      evaluated against Mycobacterium tuberculosis H37Rv as apart of TAACF TB screening
      program under direction of the US National Institute of Health, NIAID division.
      Primary screening was conducted at the single concentration, 6.25 mg/ml against
      Mycobacterium tuberculosis H37Rv (ATCC 27294) in BACTEC 12B medium using a broth
      microdilution assay, the Microplate Alamar Blue Assay (MABA). The minimum
      inhibitory concentration (MIC) determined for compounds demonstrating 90% growth
      inhibition in the primary screening. The tested compounds showed a varying degree
      of inhibitory activity (Inhibition = 0-100%). The most active compounds were 4
      methyl and 4-benzoylpiperaxinyl analogues(5b and 5g) with the same MIC value of
      3.13 micrograms/ml.

PMID- 14971312
TI  - Synthesis and fungicidal activity of some 5-aryl/aryloxymethyl-2-[5-aryl-3-methyl
      1,2,4-triazol-2-yl]-1,3,4-thiadiazoles and 5-aryl/aryloxymethyl-2[5-aryl-2
      phenylimino-1,3,4- thiadiazolin-3-yl]-1,3,4-thiadiazoles.
AB  - 5-Aryl/aryloxymethyl-2-[5-aryl-2-methyl-1,2,4-triazol-2-yl]- 1,3,4-thiadiaxoles 4
      and 5-Aryl/aryloxymethyl-2-[5-aryl-2-phenylimino-1,3,4- thiadiazolin-3-yl]-1,3,4
      thiadiazoles 5 have been obtained from the cyclocondensation of 5
      aryl/aryloxymethyl-2-arylidene hydrazino-1,3,4-thiadiazoles 3 with methyl cyanide
      and phenyl isothiocyanate respectively. Compounds 4 & 5 have been screened for
      their fungicidal activity against R. solani, F. oxysporum and P. oryzae. Based on
      screening data some structure-activity relationship is given.

PMID- 14971313
TI  - Treatment of patients with bacterial infections of the central nervous system--a
      pharmaco-economical analysis.
AB  - The meningitis and the meningoencefalitis is 29% from all of the organic diseases
      of the Central Nerve System. The actuality of this problem is determined by the
      following factors: 1. Social-only the childish group and the active group of
      workers among the adults are concerned; 2. The diseases are taking their course
      seriously with a high percentage of lethality-30%; 3. When there is untimely and
      inadequate therapy, there occurred additional manifestations of the disease.

PMID- 14971314
TI  - Synthesis and biological activity of a novel series of 4-[2'-(6'
      nitro)benzimidazolyl]benzoyl amino acids and peptides.
AB  - A series of new 4-[2'-(6'-nitro)benzimidazolyl]benzoyl amino acids and peptides
      have been synthesized by coupling the 4-[2'-(6'-nitro)benzimidazolyl]benzoic acid
      with amino acid methyl esters/dipeptides using DCC as the coupling agent. All the
      synthesized compounds were found to exhibit potent anthelmintic activity along
      with moderate antimicrobial activity.

PMID- 14971315
TI  - Influence of colon degradation of polysaccharide on the oral bioavailability of
      theophylline from controlled release hydrophilic matrices.
AB  - Hydrophilic matrices of gum karaya (GK) and guar gum (GG) using theophylline (TH)
      as a model drug were prepared for oral controlled release. In vitro release
      studies were performed for these matrix systems to find out the suitable drug
      carrier ratio, which extend the drug release up to 24 h. Promising matrix systems
      were subjected for in vitro degradation studies in the presence of rat caecal
      contents. These matrices were also evaluated for their in vivo performance in
      healthy human volunteers. Matrix systems containing 40% w/w of polysaccharide (GK
      or GG) have shown uniform and similar in vitro drug release profile for 24 h in
      the Sorenson's phosphate buffer (pH 7.4). However, TH release from GG-TH matrix
      system in the presence of rat caecal contents was significantly higher than that
      from GK-TH matrix system. This is because of the susceptibility of GG for
      degradation by microorganisms present in the rat caecal content. Though there was
      no significant difference between the peak plasma concentration (Cmax) and time
      of its occurrence (Tmax) for TH from GG-TH and GK-TH matrix systems, it was found
      that oral bioavailability of TH from former matrix was significantly higher than
      that of later. Therefore, the present study disclosed that the usage of colon
      degradable polymer offers an advantage in the design of controlled release dosage
      forms of drugs, which has good absorption properties throughout the
      gastrointestinal tract.

PMID- 14971316
TI  - [The role of macrophages in inflammation development, effects of interleukin-1,
      interleukin-6, and hypothalamo-hypophyseal system activity (a literature
      review)].

PMID- 14971317
TI  - [Diagnostic significance of determining troponin T level in blood of patients
      with myocardial infarction].

PMID- 14971318
TI  - [Biochemical analysis of children tears in herpetic keratitis].
AB  - The processes of free-radical oxidation aggravate and the antioxidant corneal
      protection worsens in children with herpetic keratitis, which is confirmed by a
      higher chemiluminescence of the lachrymal fluid and by a lower peroxidase
      activity in it. The study results are indicative of the feasibility to add the
      antioxidants to the complex therapy of herpetic keratitis. On the basis of the
      enzyme assay a method was designed to prognosticate the possibility of relapses
      of ophthalmoherpes in children.

PMID- 14971319
TI  - [Medium weight molecules in patients with external genital endometriosis].
AB  - One hundred and fifty-three women with external genital endometriosis (EM),
      stages 1-4, and 30 healthy fertile women were examined. The peripheral-blood
      serum and daily urine were tested with the level of the mean weight molecules
      (MWM) being determined spectrophotometrically at lambda = 230-300 nm. The minimal
      MWM concentrations were detected in blood in cases of the stage-1 endometrioid
      process; they were significantly lower versus those observed in the healthy women
      at the maximal urine concentrations, i.e. well above the normal value. An
      increasing MWM blood content is registered in stages 2-4 EM, which exceeds the
      normal figure, whereas MWM was minimal in urine in stage 2, it was progressively
      increasing later but did not reach the value of stage 1. The external EM was
      associated with an enhanced MWM formation; it is noteworthy, that their
      concentrations in blood serum directly correlated with a stage of the
      endometrioid process. A reliably lower MWM level in stage 1 EM is below the
      normal value, while its maximal increase in urine could be regarded as a
      compensation-adaptation reaction aimed at removing the toxic substances from the
      body. A reduced MWM discharge with urine and its growth in blood plasma were
      observed in further progressing of the endometrioid process, which is
      preconditioned by the toxic impact of MWM exerted on the nephron.

PMID- 14971320
TI  - [Analysis of protein and polysaccharide fractions in urine from patients with
      syringomyelia].

PMID- 14971321
TI  - [Morphometric study of lymphoid cells from non-Hodgkin lymphoma and reactive
      lymphadenitis].
AB  - A study of morphometric parameters of lymphoid cells reveals reliably higher
      parameters of area, perimeter as well as coefficients of shape and nucleus
      diameter of malignant cells in non-Hodgkin lymphoma versus the analogical indices
      observed in benign lymphoproliferative processes, which is an objective
      differential-diagnostic feature contributing to an accurate identification of
      lymphoproliferative lesions.

PMID- 14971322
TI  - [Serous papillary cancer of the endometrium (morphological diagnosis, DNA flow
      cytometry, clinical pattern) (a lecture)].

PMID- 14971323
TI  - [Electrokinetic properties of cells in chronic duodenal diseases].
AB  - The electrokinetic properties of erythrocytes of the duodenal and buccal
      epitheliums were studied in patients with chronic duodenitis and with duodenal
      ulcer at exacerbation in the remote period after selective proximal vagotomy; the
      diagnostic value of the studied parameters was demonstrated, the presence of
      correlation bonds between them was shown.

PMID- 14971324
TI  - [Peripheral blood parameters in patients with gastrointestinal tuberculosis].
AB  - The hemograms of 38 patients with gastrointestinal tuberculosis (GIT) and of 47
      patients with pulmonary tuberculosis variations were comparatively studied.
      Reliably valuable differences were registered in the frequency rate of deviations
      from the norm and in the mean values of hemograms' parameters of GIT patients,
      i.e. a more pronounced lower count of erythrocytes, hemoglobin and of monocyte
      lymphocyte index as well as an accelerated ESR and a disassociation between the
      accelerated ESR and the normal leukocyte count.

PMID- 14971325
TI  - [Method for determining dopamine and morphine binding sites in lymphocytes from
      human peripheral blood].
AB  - A histochemical method was designed to detect the regions of binding the dopamine
      and morphine in human peripheral blood lymphocytes. It is based on incubating the
      suspension of lymphocytes and conjugated dopamine or morphine with bull serum
      albumin (BSA) marked by horse-radish peroxidase. After incubation, smears are
      prepared from the lymphocyte suspension, which are stained by diaminobenzidine in
      the presence of hydrogen peroxide for peroxidase. The light microscope with oil
      immersion is used to count the number of lymphocytes (from among 100 hundred of
      them), which contain the peroxidase granules. Smears from the lymphocyte
      suspension, which were incubated with the BSA-peroxidase conjugate, were
      controls. The binding of peroxidase-marked ligands of dopamine and mu-opioid
      receptors with lymphocytes was oppressed by the dose-dependant preliminary
      incubation with antagonists (haloperidol, naloxone), on the basis of which the
      presence of the ligand-receptor interaction can be suggested. The number of
      bindings of dopamine and morphine in lymphocytes was shown to be reliably higher
      in the alcoholic-intoxication state versus the healthy subjects without any signs
      of alcohol consumption. The designed method is simple enough in use and does not
      require any special equipment for the receptor detection in a moderate blood
      quantity.

PMID- 14971326
TI  - [Spontaneous aggregation of thrombocytes in the risk assessment of thrombogenic
      postoperative complications in lung cancer].
AB  - The changes in spontaneous platelet aggregation (SPA), malonic dialdehyde (MDA)
      levels, total antioxidant blood volume (TABV) and total platelet count (TPC) in
      blood serum of patients with cancer of the lungs were postoperatively analyzed.
      The laboratory signs of impairments within the lipid peroxidation
      system/antioxidant protection were shown to take shape by postoperative days 7
      14. Higher blood MDA levels were accompanied by a pronounced increase of SPA and
      TPC. It was suggested to use the SPA findings as an efficient laboratory
      criterion in diagnosing the impairments occurring in the platelet-vascular
      hemostasis chain.

PMID- 14971327
TI  - [Age-related characteristics of general and specific immunity in children with
      atopic bronchial asthma from the Volga region].
AB  - The age-related peculiarities of indices of the total and specific immunity
      systems were comparatively studied in children with atopic bronchial asthma (ABA)
      at critical age intervals. The group of children aged 2 to 5 was shown to have a
      higher absolute quantity of CD3+, CD4+ and CD8+ lymphocytes, a relatively lower
      content of CD8+ and CD16+ lymphocytes, disimmunoglobulinemia, a higher level of
      total IgE (by 36.5 times), and an impaired functional activity of cells in the
      nonspecific resistance system. Higher levels of specific IgE-antibodies to pollen
      allergens were detected in 84.4% of cases in peripheral blood of ABA children;
      the content of the above antibodies (to mixed weed allergens, hemp, fescue, boon,
      bent, ryegrass, and sun-flower) were higher (p < 0.05) both in age-matched
      healthy children and in older ABA children. A 20-fold increase of the total IgE
      level, a higher CD16+ lymphocyte content a lower relative quantity of CD8+
      lymphocytes and attenuated phagocyte-activity indices were registered in the
      group of children aged 6 to 10. Apart from a 17.1-fold increase of the total IgE
      level, the attenuated phagocyte-activity parameters of neutrophils were observed
      in the group of older children (aged 11 to 15). Higher levels of specific IgE
      antibodies to food allergens were detected (in a majority of cases) in peripheral
      blood of children in 2 elder groups. Polyvalent sensitization (a higher
      production of IgE-antibodies to more than 3 allergens of different groups)
      reached 71.0-76.7% in children of various age groups.

PMID- 14971328
TI  - [A simple biological method for the fast identification of antibiotics].
AB  - A method used to determine the quantitative and qualitative determination of
      antibiotics in blood, injury discharge, in human and animal urine as well as in
      foodstuffs (meat, milk and products made of them) is described. It is based on
      using obligate, thermophilic bacteria Bacillus stearothermophilus, strains KK BKM
      B-213OD and BKM B-718 with an optimum growth at 55-60 degrees C. Meso- and
      psychrophilic bacteria cannot grow at the above temperature, therefore, the
      studied non-sterile material does not need any preliminary thermal treatment
      prior to the indicator-strain, which is highly sensitive to all widely used
      antibiotics, is sown in the test-culture bacterial lawn.

PMID- 14971330
TI  - [Clinical laboratory analysis--accuracy and reliability].

PMID- 14971329
TI  - [Optimization of serologic diagnosis of Lime borreliosis].

PMID- 14971331
TI  - Strictures increased for hospital joint ventures.

PMID- 14971332
TI  - Maximizing advocacy effectiveness in 2004.

PMID- 14971333
TI  - New tools 2003.

PMID- 14971334
TI  - Flax facts. A grain for good health.

PMID- 14971335
TI  - National Diabetes Month. Spotlight on type 2 diabetes in kids.

PMID- 14971336
TI  - Sick-day supplies. Make sure you're prepared.

PMID- 14971337
TI  - Diabetes basics. Understanding hypoglycemia.

PMID- 14971338
TI  - Meatless main dishes.

PMID- 14971339
TI  - Diabetes quiz. How much do you know about vitamins?

PMID- 14971340
TI  - With a little help from our friends.

PMID- 14971341
TI  - Christmas foods around the world.

PMID- 14971342
TI  - Diabetes resources. Calculating the holidays.

PMID- 14971343
TI  - Boning up on bone health.

PMID- 14971344
TI  - Getting to know ketones.

PMID- 14971345
TI  - Supermarket smarts. Cereal and breakfast bars.

PMID- 14971346
TI  - Traveling with diabetes.

PMID- 14971348
TI  - Health tips. Treating frostbite.

PMID- 14971347
TI  - Understanding arthritis. Joint pain, many varieties.

PMID- 14971349
TI  - New drug for women with irritable bowel syndrome.

PMID- 14971350
TI  - Mayo study: preventing diabetes may mean more exercise.

PMID- 14971351
TI  - Hearing aids. Choices for every need.

PMID- 14971352
TI  - Testosterone. An important hormone.

PMID- 14971353
TI  - Trigeminal neuralgia.

PMID- 14971354
TI  - I've recently had to stop writing in my journal because my right hand tightens
      and twists when I try to write. My doctor says it's a focal dystonia. Are there
      treatments?

PMID- 14971355
TI  - My dentist says taking better care of my teeth may have heart benefits. What's
      the connection?

PMID- 14971357
TI  - [The connection between tuberculosis and HIV].

PMID- 14971356
TI  - [Anabolic steroids and HIV].

PMID- 14971358
TI  - [New options for dosage of medications].

PMID- 14971359
TI  - [Health services covered by Medicaid].

PMID- 14971360
TI  - Cancer in the HIV-infected population.

PMID- 14971361
TI  - An overview of the biology and viral pathogenesis of lymphoproliferative
      disorders in HIV-infected patients.

PMID- 14971362
TI  - The use of antiretroviral therapy in patients undergoing treatment for HIV
      related neoplastic disease.

PMID- 14971363
TI  - Cancer and AIDS: National Cancer Institute's investment in research.

PMID- 14971364
TI  - The rise and fall of the AIDS Malignancy Consortium.

PMID- 14971365
TI  - AIDS and cancer: one patient's story.

PMID- 14971366
TI  - The origin of modern human behavior.
AB  - Archaeology's main contribution to the debate over the origins of modern humans
      has been investigating where and when modern human behavior is first recognized
      in the archaeological record. Most of this debate has been over the empirical
      record for the appearance and distribution of a set of traits that have come to
      be accepted as indicators of behavioral modernity. This debate has resulted in a
      series of competing models that we explicate here, and the traits are typically
      used as the test implications for these models. However, adequate tests of
      hypotheses and models rest on robust test implications, and we argue here that
      the current set of test implications suffers from three main problems: (1) Many
      are empirically derived from and context-specific to the richer European record,
      rendering them problematic for use in the primarily tropical and subtropical
      African continent. (2) They are ambiguous because other processes can be invoked,
      often with greater parsimony, to explain their character. (3) Many lack
      theoretical justification. In addition, there are severe taphonomic problems in
      the application of these test implications across differing spans of time. To
      provide adequate tests of these models, archaeologists must first subject these
      test implications to rigorous discussion, which is initiated here.

PMID- 14971367
TI  - Genetic Analysis Workshop II: results of incorporating a linkage disequilibrium
      parameter.
AB  - The corporation of a linkage disequilibrium parameter, delta, into linkage
      analysis is illustrated for data from Genetic Analysis Workshop II. Points from a
      joint likelihood surface are calculated and displayed on a recombination fraction
      linkage disequilibrium grid using a simple modification of LIPED. The approach is
      shown to increase the power of linkage analysis and the power of tests for
      heterogeneity of linkage for the simulated examples.

PMID- 14971368
TI  - Genetic Analysis Workshop II: pedigree analysis of a binary trait without
      assuming an underlying liability.
AB  - A model for concordance in a binary measure that does not rely on the assumption
      of an underlying latent liability dichotomized about a threshold has been
      demonstrated for twin pairs [Hannah et al, 1983]. It is extended here to
      pedigrees of arbitrary structure by making an assumption that is, for small
      incidence rates, almost equivalent to postulating that relative risks are
      multiplicative. The model is applied to the workshop data to determine the extent
      to which the known structure of the simulated models can be recovered.

PMID- 14971369
TI  - ESA's participation in the International Microgravity Laboratory (IML-2) mission.
AB  - The second International Microgravity Laboratory (IML-2) mission was a truly
      international event, paving the way for cooperation in the scientific utilisation
      of the forthcoming International Space Station. ESA provided several major
      facilities for conducting research in microgravity, as did France and Germany.
      The facilities were used jointly with scientists from the US; in exchange, NASA
      provided the mission itself. Several experiments measured and characterised the
      microgravity environment and the astronauts' response to spaceflight conditions.
      Others were in the fields of biology, biotechnology, fluid dynamics, crystal
      growth and alloy solidification, and near-critical-point investigations. Another
      important objective of the mission was to demonstrate remote payload operations
      or telescience. Using that method, principal investigators monitored and
      controlled their flight experiments from various user centres and laboratories
      across Europe. This approach is proving to be a very efficient and cost-effective
      way to conduct and optimise scientific research, and it will become increasingly
      important as long-duration access to space becomes available.

PMID- 14971370
TI  - Microgravity research during aircraft parabolic flights: the 20 ESA campaigns.
AB  - Aircraft parabolic flights provide repeated periods of up to 20 seconds of
      reduced gravity during ballistic flight manoeuvres, preceded and followed by 20
      seconds of 1.8 g. Such flights are used to conduct short microgravity
      investigations in physical and life sciences, to test instrumentation and to
      train astronauts before a spaceflight. Since 1984, ESA's Microgravity Projects
      Division has organised 20 parabolic flight campaigns using three different types
      of aircraft. More than 1700 parabolas have been flown, representing nine and half
      hours of microgravity in slices of 20 seconds, or equivalently, six low Earth
      orbits. A total of 235 experiments have been performed using this unique
      microgravity tool.

PMID- 14971371
TI  - The first parabolic flight campaign for students.
AB  - In the last week of November 1994, a different type of parabolic flight campaign
      took place: For the first time, students were given the unique opportunity of
      experiencing weightlessness. The campaign was part of the second European Week
      for Scientific Culture and the main goal was to motivate and educate the students
      rather than to obtain pure scientific and technological results as is normally
      the case in 'professional' campaigns. Twenty student experiments were chosen in a
      Europe-wide competition and the winning student teams were invited to carry out
      the experiments during a series of parabolic flights. The experiments covered a
      wide variety of disciplines ranging from general and fluid physics to material
      processing, crystal growth, and technology research. The campaign was a great
      success, all experiments worked well and the students proved to be a serious and
      motivated workforce which performed well in the rather unsettling microgravity
      environment. By learning from each other's experiments and through the unique
      personal experience of weightlessness, the students have become ambassadors for
      microgravity research. Most importantly, they have shown that we can have
      confidence in the next generation to make good use of microgravity research
      opportunities, including the International Space Station, in the future.

PMID- 14971372
TI  - Genetic Analysis Workshop II: further consideration of segregation and linkage
      analyses in Problem 3.
AB  - We analyzed disease-marker associations in Problem 3 for the Genetic Analysis
      Workshop II, using PAP for segregation analysis and LIPED for linkage analysis.
      In this report we present aspects of our analyses that are not reported in the
      summary [MacCluer et al, 1984]. Certain features that we added to the running of
      LIPED to facilitate the analysis are discussed. Furthermore, we tested for
      Mendelian transmission in the hypothetical trait locus and we calculated modified
      relative risks for marker-trait genotypes. Some of the problems involved in
      analyzing complex associations among loci are discussed.

PMID- 14971373
TI  - Ballistocraft: a novel facility for microgravity research.
AB  - One of ESA's aims is to provide the microgravity research community with various
      microgravity exposure facilities. Those facilities include drop towers, sounding
      rockets, and parabolic flights on board aircraft, in addition to orbital
      spacecraft. Microgravity flights are usually achieved using large aircraft like
      the French 'Caravelle' that offer a large payload volume and where a person can
      be present to perform the experiments and to participate as a human test-subject.
      However, the microgravity community is also very interested in a flexible,
      complementary facility that would allow frequent and repetitive exposure to
      microgravity for a laboratory-type of payload. ESA has therefore undertaken a
      study of the potential of using a 'ballistocraft', a small unmanned aircraft, to
      provide a low-cost facility for short-duration (30-40 seconds) microgravity
      experimentation. Fokker Space & Systems performed the study under an ESA
      contract, supported by Dutch national funding. To assess the ballistocraft, a
      simple breadboard of the facility was built and flight tests were performed. The
      ability of the on-board controller to achieve automated parabolic flights was
      demonstrated, and the performance of the controller in one-g level flights, and
      in flights with both zero-g and partial-g setpoints, was evaluated. The partial-g
      flights are a unique and valuable feature of the facility.

PMID- 14971374
TI  - Genetic Analysis Workshop II: combined segregation, linkage, and association
      analysis.
AB  - A combined segregation, linkage, and association analysis using the program
      COMBIN was performed on the simulated pedigree data prepared for the Second
      Genetic Analysis Workshop. The model used in COMBIN is described and the
      presented results illustrate its effectiveness in the analysis of such data.
      Linkage analysis was performed and maps for each linkage group are presented.

PMID- 14971375
TI  - AIDS: no end in sight.

PMID- 14971376
TI  - Genetic Analysis Workshop II: segregation and linkage analysis.
AB  - Familial segregation and linkage analyses were performed on two sets of the
      Genetic Analyses Workshop II data. The salient features of the mode of
      inheritance of the disease trait and its linkage/association with polymorphic
      markers and also marker-marker linkages were delineated using statistical-genetic
      techniques.

PMID- 14971377
TI  - AACR-NCL-EORTC International Conference on Molecular Targets and Cancer
      Therapeutics.

PMID- 14971378
TI  - Genetic Analysis Workshop II: multiple-locus segregation analysis incorporating
      linkage markers.
AB  - The workshop data were examined using a newly developed methodology (MILINK,
      Risch, 1984) for combined segregation, linkage, and association analysis of a
      complex disease trait in pedigree data. Results from problems two and three
      suggest that the method is powerful both for determining mode of disease
      inheritance and for resolution of linkage disequilibrium versus pleiotrophy (with
      epistasis) of marker alleles.

PMID- 14971379
TI  - [Sebald Brugmans and hospital gangrene].
AB  - Sebald Justinus Brugmans, Professor at Leyden University and from 1795 on
      Director of the 'Geneeskundig Bureau der Bataafsche Republiek', organized all
      necessary facilities in the Leyden Military Hospital. His appointment, 1811, as
      inspector-general of the French Imperial Military Health-Service, seemed to be
      the next step in a brilliant career of more than 25 years. He became a leading
      expert in the fight against hospital-gangrene and its prevention, not in the
      least because of the enthusiastic reception of his treatise on gangrene (1814) in
      which he meticulously analyzed and explained the causes of this dreadful disease.
      He completed his entry with a thorough evaluation of all possible and well
      experienced sanitary regulations. He was convinced of the contagious character of
      the disease. Quite unusual at the time, he used the terms "miasma" and
      "contagium" interchangeably. Maybe partly for that reason, his work was
      instrumental in convincing most later authors that gangrene was a contagious
      disease. Brugmans' fame was established forever after tha Battle of Waterloo
      (June 1815).

PMID- 14971380
TI  - In vitro fertility proposals by Bush council stir controversy.

PMID- 14971381
TI  - How some patients in new-drug trials can get cut off.

PMID- 14971382
TI  - Trial will test privacy rules for health files.

PMID- 14971383
TI  - Italian debate on fertility bill raises issue of church influence.

PMID- 14971384
TI  - Facing up to the inevitable, in search of a good death.

PMID- 14971385
TI  - Stem-cell law welcomed by researchers.

PMID- 14971386
TI  - Ambiguous gifts: when patients give and doctors take.

PMID- 14971387
TI  - No guardian for a fetus, court rules.

PMID- 14971388
TI  - Medical research dealings explored by a Senate panel.

PMID- 14971389
TI  - Wisconsin senate approves tax deduction for organ donors.

PMID- 14971390
TI  - Subverting U.S. health.

PMID- 14971391
TI  - Stealth merger: drug companies and government medical research.

PMID- 14971392
TI  - Bibliography. Current world literature. Hematology and oncology.

PMID- 14971393
TI  - Bibliography. Current world literature. Orthopedics.

PMID- 14971394
TI  - Bibliography. Current world literature. infectious diseases and immunization.

PMID- 14971395
TI  - A vital fluid: risk, controversy and the politics of blood donation in the era of
      "mad cow disease".
AB  - This article examines the reasons for, and likely impact of, the decision by the
      US and other countries to permanently defer blood donors who have spent time in
      Britain or Europe, for fear they may transmit new variant Creutzfeldt-Jakob
      disease (vCJD), the human form of "mad cow disease". It begins by discussing how
      vCJD and blood transfusion are linked, and how these have been translated into
      policy. First, maintaining a safe and stable supply of blood entails not only
      maintaining the trust of recipients in the system, but also that of donors, who
      need to be assured that their blood will be welcomed and used. Often, the
      balance, once upset, is regained by sacrificing donors, but accompanying costs
      might also be high. Second, the article highlights the impact of various forms of
      globalization -of commerce, disease and travel, and immigration- on blood
      policies and public and policy attitudes. Third, it assesses the decision by the
      US to restrict blood donations from Europeans and travelers to combat such a
      pervasive risk. The conclusion discusses how donor deferral policies may be
      interpreted by the public in the light of earlier discussions, and raises issues
      for future research.

PMID- 14971396
TI  - Headspace solvent microextraction of trihalomethane compounds into a single drop.
AB  - Headspace solvent microextraction (HSME) into a single drop is developed for the
      determination of six trihalomethanes, CH2Cl2, CHCl3, C4H9Cl, CCl4, C2HCl3, and
      C2Cl4, in aqueous solution. A drop of benzyl alcohol containing bromoform, as an
      internal standard, is used for extraction. The analytes are extracted by
      suspending a 3-microL drop directly from the needle of a microsyringe. The needle
      passes through the septum of a vessel, and the needle tip appears above the
      surface of the solution. After the prescribed extraction time, the drop is drawn
      back into the syringe. The syringe is then removed, and its content is injected
      directly into a gas chromatography column for analysis. The main parameters
      affecting the HSME process, such as stirring speed, microdrop volume, sample
      solution temperature, microsyringe needle temperature, sample volume, solution
      pH, extracting solvent, and ionic strength of the solution, are studied. Also,
      the linear range and precision of the method are examined.

PMID- 14971397
TI  - Assortive mating for personaltiy traits, educational level, religious
      affiliation, height, weight, adn body mass index in parents of Korean twin
      sample.
AB  - The degree of assortative mating for psychological and physical traits in Asian
      societies in relatively unknown. The present study examined assortative mating
      for educational level, personality traits, religious affiliation, height, weight,
      and body mass index in a korean sample. Age-adjusted spouse correlations were
      high for educational level (r = .63) and religious affiliation (r = .67), modest
      for most personality traits (rs = -.01 to .26), and trivial for height (r = .04),
      weight (r = .05)m and body mass index (r = .11). These results were remarkably
      similar to those found from the western samples. Implications of the present
      findings in behavior genetic studies and human mating patterns were briefly
      discussed.

PMID- 14971401
TI  - Beyond public perceptions of gene technology: community participation in public
      policy in Australia.
AB  - Public policy assumptions, which view "the public" as passive consumers, are
      deeply flawed. "The public" are, in fact, active citizens, who constitute the
      innovation end of the seamless web of relationships, running from research and
      development laboratory to shop, hospital or farm, or local neighborhood. "The
      public" do not receive the impact of technology; they are the impact, in that
      they determine with gene technology (GT) developers and sellers what happens to
      the technology in our society. In doing so, they, or more rightly we, exercise
      particular, contextual knowledges and actions. We suggest that it is the
      ignorance of this aspect of innovation in policy processes that produces the
      distrust and resentment that we found in our interviews with "publics" interested
      in gene technology. This is consistent with Beck's description of the deep
      structural states of risk and fear in modern advanced societies with respect to
      new technologies, such as gene technology. Only policy processes that recognize
      the particular, local and contextual knowledges of "the public", which co
      construct innovation, can achieve deep, social structural consideration of gene
      technology. And only such a deep consideration can avoid the polarized attitudes
      and deep suspicions that we have seen arise in places such as Britain. Such
      consideration needs the type of processes that involve active consultation and
      inclusion of "the public" in government and commercial innovation, the so-called
      deliberative and inclusionary processes (DIPs), such as consensus conferences and
      citizen juries. We suggest some measures that could be tried in Australia, which
      would take us further down the path of participation toward technological
      citizenship.

PMID- 14971402
TI  - Lay experts and the politics of breast implants.
AB  - This paper discusses the controversy around breast implants in the United States
      and Europe. It focuses on the emergence of consumer and support groups for women
      and offers an analysis of the role they have played in recent policy developments
      in UK and Europe. The politics of breast implants is seen as a politics of
      knowledge in which scientific expertise has consistently been deployed in ways
      that minimize the credibility and legitimacy of women's accounts of their bodies
      and illness experiences. These women have been doubly disadvantaged in a policy
      debate that turns on scientific controversy and uncertainty. This implies a
      gendered dynamic to the changing relations of knowledge and expertise. The paper
      contributes to an understanding of the relations between regulators,
      manufacturers, users, and clinicians in the global medical device industry and to
      wider debates around the public understanding of science.

PMID- 14971403
TI  - A painting of medical interest.

PMID- 14971404
TI  - The aspirin story.

PMID- 14971405
TI  - Cancer therapy and military cold-war research: crossing epistemological and
      ethical boundaries.

PMID- 14971406
TI  - Asbestos mining and occupational disease in Southern Rhodesia/Zimbabwe, 1915-98.

PMID- 14971407
TI  - Birth can be a hazardous journey: electronic fetal monitoring does not help.

PMID- 14971408
TI  - The use of first trimester ultrasound.

PMID- 14971409
TI  - Attitudes toward life and death among Chinese adolescents: the Chinese version of
      the multi-attitude suicide tendency scale.
AB  - The psychometric properties of the Chinese version of the Multi-Attitude Suicide
      Tendency Scale were examined in a sample of 415 Chinese adolescents. Confirmatory
      factor analyses of the present data disconfirmed the original 4-factor structure.
      Exploratory factor analysis was then conducted to explore the underlying
      structure of the data set. A revised 4-factor structure, with a number of
      differences in item factor loadings, was obtained for the present sample. The
      scale also demonstrated good internal consistency and convergent validity with
      the Depression Self-Rating Scale and Suicidal Behaviors Questionnaire. Distinct
      profiles of the scale were shown on non-suicidals, suicide ideators, and suicide
      attempters. Discrepant findings from previous work were discussed.

PMID- 14971410
TI  - Need for primate models in biomedical research.

PMID- 14971411
TI  - Science, ethics and regulation in primate research.

PMID- 14971412
TI  - "Living in the dragon's shadow" fathers' experiences of a child's life-limiting
      illness.
AB  - Grounded theory methods were used to study the experiences of 8 bereaved fathers
      whose children received care in a home-based hospice program. In-depth,
      unstructured interviews were audiotaped, transcribed, and coded for themes and
      categories. Every aspect of fathers' lives was affected by their experiences,
      which were described in metaphoric terms as living in a dragon's shadow. Fathers
      dealt with life in the dragon's shadow by battling the dragon (the illness)--the
      core social process. Battling was a conscious, active, continuous process that
      required strength, willpower, and work. Battling occurred within the context of
      fathers' experiences with fathering and fatherhood and was characterized by 3
      aspects: battling with uncertainty, battling with responsibility, and battling
      with everyday disruption. Fathers were assisted by supportive work environments
      and by supportive relationships with health care providers. Unsatisfactory
      relationships with medical personnel compounded fathers' battling with life in
      the dragon's shadow.

PMID- 14971413
TI  - Reproductive behavior in wild baboons.

PMID- 14971414
TI  - Use of a baboon model for research in human contraception.

PMID- 14971415
TI  - Subhuman primates as models for the development of male contraceptives.

PMID- 14971416
TI  - The male vervet monkey: sperm characteristics and use in reproductive research.

PMID- 14971417
TI  - Predictors of suicidal behavior in a sample of Turkish suicide attempters.
AB  - In a Turkish sample, 100 suicide attempters, were compared with 60 healthy
      controls on measures of hopelessness, depression, and suicidal ideation. Suicide
      attempters were more depressive, more hopeless, and displayed greater suicidal
      ideation than healthy controls. Depression severity rather than hopelessness
      correlated with suicidal intent. Suicide lethality was independent of depression
      severity, hopelessness, and suicidal ideation and intent, suggesting that
      lethality is likely due to chance.

PMID- 14971418
TI  - In vitro growth and maturation of oocytes in human and non-human primates.

PMID- 14971419
TI  - Non-human primates as a model for reproductive aging and human infertility.

PMID- 14971420
TI  - Ovarian stimulation, egg aspiration, in vitro fertilization and embryo transfer
      in the baboon (Papio anubis): a pilot project at the Institute of Primate
      Research, Nairobi, Kenya.

PMID- 14971421
TI  - Death on campuses: common postvention strategies in higher education.
AB  - The purpose of this article is to expand on E. S. Zinner's (1985a) postvention
      recommendations and, given R. L. Wrenn's (1991a) conclusion that 62% of
      institutions have not created a postvention plan, describe how to develop a death
      response team (DRT) to deal with campus fatalities. The basic components of a DRT
      that are examined include the team's development, family and faculty
      notification, psychological first aid to assist students, community postvention
      strategies, documentation, and staff training. Information on how postvention
      strategies vary according to the student's group membership, type of death, and
      institution's resources is also presented. It is concluded that present
      postvention literature has expanded on E. S. Zinner's suggestions, although
      additional research is still needed. Recommendations are made to modify
      counseling training programs, obtain the support of key administrators, recognize
      that a DRT cannot plan for everything, and provide ongoing bereavement support
      for students

PMID- 14971422
TI  - Law and ethics.

PMID- 14971423
TI  - Physical activity and bone strength.

PMID- 14971425
TI  - What's hot in hospital design.

PMID- 14971424
TI  - Ouabain exerts biphasic effects on connexin functionality and expression in
      vascular smooth muscle cells.
AB  - 1. We have compared the effects of ouabain on the maintenance of gap junctional
      communication in rat aortic A7r5 smooth muscle cells, monkey COS-1 fibroblasts
      and human HeLa epithelial cells. 2. Ouabain (1 mM) interrupted dye coupling
      between confluent A7r5 cells within approximately 1 h, and high concentrations of
      ouabain were similarly required to reduce coupling between COS-1 cells selected
      to express the rat alpha1 Na+/K+-ATPase subunit, which is ouabain resistant. By
      contrast, low concentrations of ouabain (1-10 microM) attenuated dye transfer in
      wild-type COS-1 and HeLa cells, whose endogenous alpha1 subunits possess
      relatively high affinity for the glycoside (Ki approximately 0.3 vs approximately
      100 microM) Ouabain-induced reductions in dye transfer therefore correlated with
      the ability of the glycoside to bind to the Na+/K+-ATPase isoenzymes expressed in
      these different cell lines. 3. No consistent relationship between inhibition of
      intercellular dye transfer and secondary changes in [Ca2+]i or pHi could be
      identified following incubation with ouabain. 4. In separate experiments, the
      effects of ouabain on real-time trafficking of connexin (Cx) protein were
      monitored by time-lapse microscopy of A7r5 cells transfected to express a
      fluorescent Cx43-green fluorescent protein (GFP) and the ability of the glycoside
      to modulate endogenous expression of Cx40 and Cx43 evaluated in A7r5 cells by
      immunochemical and Western blot analysis. 5. Ouabain (1 mM) depressed vesicular
      trafficking of Cx43-GFP after approximately 1 h, and caused a time-dependent loss
      of endogenous Cx40 and Cx43 protein that was first evident at 2 h and almost
      complete after 4 h. These effects of ouabain on Cx expression were reversed 90
      min following washout of the glycoside. 6. We conclude that ouabain exerts
      biphasic effects on intercellular communication that involve an initial decrease
      in gap junctional permeability followed by a global reduction in the expression
      of Cx protein. Further studies are necessary to establish to what extent these
      actions of ouabain reflect inversion of the normal [Na+]i/[K+]i ratio and/or
      conversion of the Na+/K+-ATPase into a general signal transducer that regulates
      downstream protein synthesis.

PMID- 14971426
TI  - [Significance of guidelines by specialty societies as clinical pathway in
      medicine. Malpractice liability of an indication (BGB section 823)].

PMID- 14971427
TI  - [Episodic attacks of vertigo].

PMID- 14971428
TI  - [Application of multiple arbitrary amplification profiling to the identification
      of Chinese medicinal herbs].

PMID- 14971429
TI  - IOC consensus statement on sports nutrition 2003.

PMID- 14971430
TI  - Carbohydrates and fat for training and recovery.
AB  - An important goal of the athlete's everyday diet is to provide the muscle with
      substrates to fuel the training programme that will achieve optimal adaptation
      for performance enhancements. In reviewing the scientific literature on post
      exercise glycogen storage since 1991, the following guidelines for the training
      diet are proposed. Athletes should aim to achieve carbohydrate intakes to meet
      the fuel requirements of their training programme and to optimize restoration of
      muscle glycogen stores between workouts. General recommendations can be provided,
      preferably in terms of grams of carbohydrate per kilogram of the athlete's body
      mass, but should be fine-tuned with individual consideration of total energy
      needs, specific training needs and feedback from training performance. It is
      valuable to choose nutrient-rich carbohydrate foods and to add other foods to
      recovery meals and snacks to provide a good source of protein and other
      nutrients. These nutrients may assist in other recovery processes and, in the
      case of protein, may promote additional glycogen recovery when carbohydrate
      intake is suboptimal or when frequent snacking is not possible. When the period
      between exercise sessions is < 8 h, the athlete should begin carbohydrate intake
      as soon as practical after the first workout to maximize the effective recovery
      time between sessions. There may be some advantages in meeting carbohydrate
      intake targets as a series of snacks during the early recovery phase, but during
      longer recovery periods (24 h) the athlete should organize the pattern and timing
      of carbohydrate-rich meals and snacks according to what is practical and
      comfortable for their individual situation. Carbohydrate-rich foods with a
      moderate to high glycaemic index provide a readily available source of
      carbohydrate for muscle glycogen synthesis, and should be the major carbohydrate
      choices in recovery meals. Although there is new interest in the recovery of
      intramuscular triglyceride stores between training sessions, there is no evidence
      that diets which are high in fat and restricted in carbohydrate enhance training.

PMID- 14971431
TI  - Pre-exercise carbohydrate and fat ingestion: effects on metabolism and
      performance.
AB  - A key goal of pre-exercise nutritional strategies is to maximize carbohydrate
      stores, thereby minimizing the ergolytic effects of carbohydrate depletion.
      Increased dietary carbohydrate intake in the days before competition increases
      muscle glycogen levels and enhances exercise performance in endurance events
      lasting 90 min or more. Ingestion of carbohydrate 3-4 h before exercise increases
      liver and muscle glycogen and enhances subsequent endurance exercise performance.
      The effects of carbohydrate ingestion on blood glucose and free fatty acid
      concentrations and carbohydrate oxidation during exercise persist for at least 6
      h. Although an increase in plasma insulin following carbohydrate ingestion in the
      hour before exercise inhibits lipolysis and liver glucose output, and can lead to
      transient hypoglycaemia during subsequent exercise in susceptible individuals,
      there is no convincing evidence that this is always associated with impaired
      exercise performance. However, individual experience should inform individual
      practice. Interventions to increase fat availability before exercise have been
      shown to reduce carbohydrate utilization during exercise, but do not appear to
      have ergogenic benefits.

PMID- 14971432
TI  - Fluid and fuel intake during exercise.
AB  - The amounts of water, carbohydrate and salt that athletes are advised to ingest
      during exercise are based upon their effectiveness in attenuating both fatigue as
      well as illness due to hyperthermia, dehydration or hyperhydration. When
      possible, fluid should be ingested at rates that most closely match sweating
      rate. When that is not possible or practical or sufficiently ergogenic, some
      athletes might tolerate body water losses amounting to 2% of body weight without
      significant risk to physical well-being or performance when the environment is
      cold (e.g. 5-10 degrees C) or temperate (e.g. 21-22 degrees C). However, when
      exercising in a hot environment ( > 30 degrees C), dehydration by 2% of body
      weight impairs absolute power production and predisposes individuals to heat
      injury. Fluid should not be ingested at rates in excess of sweating rate and thus
      body water and weight should not increase during exercise. Fatigue can be reduced
      by adding carbohydrate to the fluids consumed so that 30-60 g of rapidly absorbed
      carbohydrate are ingested throughout each hour of an athletic event. Furthermore,
      sodium should be included in fluids consumed during exercise lasting longer than
      2 h or by individuals during any event that stimulates heavy sodium loss (more
      than 3-4 g of sodium). Athletes do not benefit by ingesting glycerol, amino acids
      or alleged precursors of neurotransmitter. Ingestion of other substances during
      exercise, with the possible exception of caffeine, is discouraged. Athletes will
      benefit the most by tailoring their individual needs for water, carbohydrate and
      salt to the specific challenges of their sport, especially considering the
      environment's impact on sweating and heat stress.

PMID- 14971433
TI  - Fluid and electrolyte needs for preparation and recovery from training and
      competition.
AB  - For a person undertaking regular exercise, any fluid deficit that is incurred
      during one exercise session can potentially compromise the next exercise session
      if adequate fluid replacement does not occur. Fluid replacement after exercise
      can, therefore, frequently be thought of as hydration before the next exercise
      bout. The importance of ensuring euhydration before exercise and the potential
      benefits of temporary hyperhydration with sodium salts or glycerol solutions are
      also important issues. Post-exercise restoration of fluid balance after sweat
      induced dehydration avoids the detrimental effects of a body water deficit on
      physiological function and subsequent exercise performance. For effective
      restoration of fluid balance, the consumption of a volume of fluid in excess of
      the sweat loss and replacement of electrolyte, particularly sodium, losses are
      essential. Intravenous fluid replacement after exercise has been investigated to
      a lesser extent and its role for fluid replacement in the dehydrated but
      otherwise well athlete remains equivocal.

PMID- 14971434
TI  - Protein and amino acids for athletes.
AB  - The main determinants of an athlete's protein needs are their training regime and
      habitual nutrient intake. Most athletes ingest sufficient protein in their
      habitual diet. Additional protein will confer only a minimal, albeit arguably
      important, additional advantage. Given sufficient energy intake, lean body mass
      can be maintained within a wide range of protein intakes. Since there is limited
      evidence for harmful effects of a high protein intake and there is a metabolic
      rationale for the efficacy of an increase in protein, if muscle hypertrophy is
      the goal, a higher protein intake within the context of an athlete's overall
      dietary requirements may be beneficial. However, there are few convincing outcome
      data to indicate that the ingestion of a high amount of protein (2-3 g x kg(-1)
      BW x day(-1), where BW = body weight) is necessary. Current literature suggests
      that it may be too simplistic to rely on recommendations of a particular amount
      of protein per day. Acute studies suggest that for any given amount of protein,
      the metabolic response is dependent on other factors, including the timing of
      ingestion in relation to exercise and/or other nutrients, the composition of
      ingested amino acids and the type of protein.

PMID- 14971435
TI  - Dietary antioxidants and exercise.
AB  - Muscular exercise promotes the production of radicals and other reactive oxygen
      species in the working muscle. Growing evidence indicates that reactive oxygen
      species are responsible for exercise-induced protein oxidation and contribute to
      muscle fatigue. To protect against exercise-induced oxidative injury, muscle
      cells contain complex endogenous cellular defence mechanisms (enzymatic and non
      enzymatic antioxidants) to eliminate reactive oxygen species. Furthermore,
      exogenous dietary antioxidants interact with endogenous antioxidants to form a
      cooperative network of cellular antioxidants. Knowledge that exercise-induced
      oxidant formation can contribute to muscle fatigue has resulted in numerous
      investigations examining the effects of antioxidant supplementation on human
      exercise performance. To date, there is limited evidence that dietary
      supplementation with antioxidants will improve human performance. Furthermore, it
      is currently unclear whether regular vigorous exercise increases the need for
      dietary intake of antioxidants. Clearly, additional research that analyses the
      antioxidant requirements of individual athletes is needed.

PMID- 14971436
TI  - Dietary supplements.
AB  - For the athlete training hard, nutritional supplements are often seen as
      promoting adaptations to training, allowing more consistent and intensive
      training by promoting recovery between training sessions, reducing interruptions
      to training because of illness or injury, and enhancing competitive performance.
      Surveys show that the prevalence of supplement use is widespread among sportsmen
      and women, but the use of few of these products is supported by a sound research
      base and some may even be harmful to the athlete. Special sports foods, including
      energy bars and sports drinks, have a real role to play, and some protein
      supplements and meal replacements may also be useful in some circumstances. Where
      there is a demonstrated deficiency of an essential nutrient, an increased intake
      from food or from supplementation may help, but many athletes ignore the need for
      caution in supplement use and take supplements in doses that are not necessary or
      may even be harmful. Some supplements do offer the prospect of improved
      performance; these include creatine, caffeine, bicarbonate and, perhaps, a very
      few others. There is no evidence that prohormones such as androstenedione are
      effective in enhancing muscle mass or strength, and these prohormones may result
      in negative health consequences, as well as positive drug tests. Contamination of
      supplements that may cause an athlete to fail a doping test is widespread.

PMID- 14971437
TI  - Exercise, nutrition and immune function.
AB  - Strenuous bouts of prolonged exercise and heavy training are associated with
      depressed immune cell function. Furthermore, inadequate or inappropriate
      nutrition can compound the negative influence of heavy exertion on
      immunocompetence. Dietary deficiencies of protein and specific micronutrients
      have long been associated with immune dysfunction. An adequate intake of iron,
      zinc and vitamins A, E, B6 and B12 is particularly important for the maintenance
      of immune function, but excess intakes of some micronutrients can also impair
      immune function and have other adverse effects on health. Immune system
      depression has also been associated with an excess intake of fat. To maintain
      immune function, athletes should eat a well-balanced diet sufficient to meet
      their energy requirements. An athlete exercising in a carbohydrate-depleted state
      experiences larger increases in circulating stress hormones and a greater
      perturbation of several immune function indices. Conversely, consuming 30-60 g
      carbohydrate x h(-1) during sustained intensive exercise attenuates rises in
      stress hormones such as cortisol and appears to limit the degree of exercise
      induced immune depression. Convincing evidence that so-called 'immune-boosting'
      supplements, including high doses of antioxidant vitamins, glutamine, zinc,
      probiotics and Echinacea, prevent exercise-induced immune impairment is currently
      lacking.

PMID- 14971438
TI  - Nutritional strategies to influence adaptations to training.
AB  - This article highlights new nutritional concerns or practices that may influence
      the adaptation to training. The discussion is based on the assumption that the
      adaptation to repeated bouts of training occurs during recovery periods and that
      if one can train harder, the adaptation will be greater. The goal is to maximize
      with nutrition the recovery/adaptation that occurs in all rest periods, such that
      recovery before the next training session is complete. Four issues have been
      identified where recent scientific information will force sports nutritionists to
      embrace new issues and reassess old issues and, ultimately, alter the nutritional
      recommendations they give to athletes. These are: (1) caffeine ingestion; (2)
      creatine ingestion; (3) the use of intramuscular triacylglycerol (IMTG) as a fuel
      during exercise and the nutritional effects on IMTG repletion following exercise;
      and (4) the role nutrition may play in regulating the expression of genes during
      and after exercise training sessions. Recent findings suggest that low doses of
      caffeine exert significant ergogenic effects by directly affecting the central
      nervous system during exercise. Caffeine can cross the blood-brain barrier and
      antagonize the effects of adenosine, resulting in higher concentrations of
      stimulatory neurotransmitters. These new data strengthen the case for using low
      doses of caffeine during training. On the other hand, the data on the role that
      supplemental creatine ingestion plays in augmenting the increase in skeletal
      muscle mass and strength during resistance training remain equivocal. Some
      studies are able to demonstrate increases in muscle fibre size with creatine
      ingestion and some are not. The final two nutritional topics are new and have not
      progressed to the point that we can specifically identify strategies to enhance
      the adaptation to training. However, it is likely that nutritional strategies
      will be needed to replenish the IMTG that is used during endurance exercise. It
      is not presently clear whether the IMTG store is chronically reduced when
      engaging in daily sessions of endurance training or if this impacts negatively on
      the ability to train. It is also likely that the increased interest in gene and
      protein expression measurements will lead to nutritional strategies to optimize
      the adaptations that occur in skeletal muscle during and after exercise training
      sessions. Research in these areas in the coming years will lead to strategies
      designed to improve the adaptive response to training.

PMID- 14971439
TI  - Protein and amino acid requirements of athletes.

PMID- 14971440
TI  - Exertional hyponatraemia.

PMID- 14971441
TI  - Predication of Fhhh potential in PTA wastewater treatment.
AB  - Ebis is the intelligent environmental biotechnological informatics software
      developed for judging the effectiveness of the microorganism strain in the
      industrial wastewater treatment system(IWTS) at the optimal status. The
      parameter, as the objective function for the judgment, is the minimum reactor
      volume(Vmin) calculated by Ebis for microorganism required in wastewater
      treatment. The rationality and the universality of Ebis were demonstrated in the
      domestic sewage treatment system(DSTS) with the data published in USA and China
      at first,then Fhhh strain's potential for treating the purified terephthalic
      acid(PTA) was proved. It suggests that Ebis would be useful and universal for
      predicating the technique effectiveness in both DSTS and IWTS.

PMID- 14971442
TI  - Phosphorus release from phosphate rock and iron phosphate by low-molecular-weight
      organic acids.
AB  - Low-molecular-weight(LMW) organic acids widely exist in soils, particularly in
      the rhizosphere. A series of batch experiments were carried out to investigate
      the phosphorus release from rock phosphate and iron phosphate by low-molecular
      weight organic acids. Results showed that citric acid had the highest capacity to
      solubilize P from both rock and iron phosphate. P solubilization from rock
      phosphate and iron phosphate resulted in net proton consumption. P release from
      rock phosphate was positively correlated with the pKa values. P release from iron
      phosphate was positively correlated with Fe-organic acid stability constants
      except for aromatic acids, but was notcorrelated with pKa. Increase in the
      concentrations of organic acids enhanced P solubilization from both rock and iron
      phosphate almost linearly. Addition of phenolic compounds further increased the P
      release from iron phosphate. Initial solution pH had much more substantial effect
      on P release from rock phosphate than from iron phosphate.

PMID- 14971443
TI  - Characteristics of metal enrichment in Deep Bay, Hong Kong.
AB  - Sediment cores, suspended particles and overlying water were collected in Deep
      Bay, Hong Kong. Enrichment of Zn in surface sediments in the landward direction
      and the decreasing of exchangeable Cd, Ni and Zn in sediment from the inner bay
      to the outer bay indicated the influence of anthropogenic pollutants discharged
      from the riparian runoffs.

PMID- 14971444
TI  - Start-up of anaerobic ammonia oxidation bioreactor with nitrifying activated
      sludge.
AB  - The anaerobic ammonia oxidation(Anammox) bioreactor was successfully started up
      with the nitrifying activated sludge. After anaerobically operated for 105 d, the
      bioreactor reached a good performance with removal percentage of both ammonia and
      nitrite higher than 95% and volumetric total nitrogen removal as high as 149.55
      mmol/( L.d). The soft padding made an important contribution to the high
      efficiency and stability because it held a large amount of biomass in the
      bioreactor.

PMID- 14971445
TI  - Optimization of enrichment processes of pentachlorophenol (PCP) from water
      samples.
AB  - The method of enriching PCP(pentachlorophenol) from aquatic environment by solid
      phase extraction(SPE) was studied. Several factors affecting the recoveries of
      PCP, including sample pH, eluting solvent, eluting volume and flow rate of water
      sample, were optimized by orthogonal array design(OAD). The optimized results
      were sample pH 4; eluting solvent, 100% methanol; eluting solvent volume, 2 ml
      and flow rate of water sample, 4 ml/min. A comparison is made between SPE and
      liquid-liquid extraction(LLE) method. The recoveries of PCP were in the range of
      87.6%-133.6% and 79%-120.3% for SPE and LLE, respectively. Important advantages
      of the SPE compared with the LLE include the short extraction time and reduced
      consumption of organic solvents. SPE can replace LLE for isolating and
      concentrating PCP from water samples.

PMID- 14971446
TI  - Application of TLSER method in predicting the aqueous solubility and n
      octanol/water partition coefficient of PCBs, PCDDs and PCDFs.
AB  - The theoretical linear solvation energy relationship(TLSER) approach was adopted
      to predict the aqueous solubility and n-octanol/water partition coefficient of
      three groups of environmentally important chemicals-polychlorinated
      biphenyls(PCBs), polychlorinated dibenzodioxins and dibenzofurans (PCDDs and
      PCDFs). For each compound, five quantum parameters were calculated using AM1
      semiempirical molecular orbital methods and used as structure descriptors:
      average molecular polarizability(alpha), energy of the lowest unoccupied
      molecular orbit( E(LUMO)), energy of the highest occupied molecular orbit(
      E(HOMO)), the most positive charge on a hydrogen atom (q+), and the most negative
      atomic partial charge(q-) in the solute molecule. Then standard independent
      variables in TLSER equation was extracted and two series of quantitative
      equations between these quantum parameters and aqueous solubility and n
      octanol/water partition coefficient were obtained by stepwise multiple linear
      regression(MLR) method. The developed equations have both quite high accuracy and
      explicit meanings. And the cross-validation test illustrated the good predictive
      power and stability of the established models. The results showed that TLSER
      could be used as a promising approach in the estimation of partition and
      solubility properties of macromolecular chemicals, such as persistent organic
      pollutants.

PMID- 14971447
TI  - Biodegradation of mixture of VOC's in a biofilter.
AB  - Volatile organic compounds(VOC' s) in air have become major concern in recent
      years. Biodegradation of a mixture of ethanol and methanol vapor was evaluated in
      a laboratory biofilter with a bed of compost and polystyrene particles using an
      acclimated mixed culture. The continuous performance of the biofilter was studied
      with different proportion of ethanol and methanol at different initial
      concentration and flow rates. The result showed significant removal for both
      ethanol and methanol, which were composition dependent. The presence of either
      compound in the mixture inhibited the biodegradation of the other.

PMID- 14971448
TI  - Pollution characteristics of the recent sediments in the Hangzhou section of the
      Grand Canal, China.
AB  - Spatial distribution of heavy metals, arsenic and organic matter in recent
      sediments in the Hangzhou section of the Grand Canal and their relationships were
      analyzed. The results showed that the concentrations of heavy metals and organic
      matters varied widely along the canal, and the average geological accumulation
      factors decreased in the following orders: organic carbon(2.6), zinc(2.1),
      cadmium (2.0), copper(1.5), lead(1.1), nitrogen(0.9), mercury (0.8),
      phosphorus(0.4), arsenic(0.2) and chromium(0). Content of heavy metals and
      organic carbon in the top 10 cm layer were lower than that of lower layers,
      except for mercury and organic carbon in the S9 section. Contents of organic
      carbon in the top 50 cm layer of the mud sediments are significantly higher than
      those underneath. In the bottom mud layer, there is a concentration peak of the
      pollutants. In the mud sediments of the canal, cadmium mainly occurred in the Fe
      and Mn oxide fraction, copper in the organic fraction, lead in the Fe and Mn
      oxide fraction, and zinc in the carbonate and the Fe and Mn oxide fraction.

PMID- 14971449
TI  - Automatic and continuous measurement of aerosol properties in Dunhuang, China.
AB  - Ground-based simultaneous observations of sun direct and scattering radiation
      were carried out in Dunhuang for nearly 2 years. Aerosol optical depth, Angstrom
      wavelength exponent and size distribution were obtained from solar extinction and
      sky radiation. Water vapor content was obtained from sun direct radiation
      measurement at 940 nm. Relationship between aerosol properties and water vapor
      was discussed. Results showed that distinct seasonality of aerosol optical depth
      and Angstrom wavelength exponent was corresponding to seasonal variation of dust
      activity. Aerosol relative size distribution kept stable and volume concentration
      change was the reason resulting in variation of aerosol optical depth. Water
      vapor had minor effects on aerosol optical and physical properties.

PMID- 14971450
TI  - Radarsat observations and forecasting of oil slick trajectory movements.
AB  - RADARSAT data have a potential role for coastal pollution monitoring. This study
      presents a new approach to detect and forecast oil slick trajectory movements.
      The oil slick trajectory movements is based on the tidal current effects and
      Fay's algorithm for oil slick spreading mechanisms. The oil spill trajectory
      model contains the integration between Doppler frequency shift model and
      Lagrangian model. Doppler frequency shift model implemented to simulate tidal
      current pattern from RADARSAT data while the Lagrangian model used to predict oil
      spill spreading pattern. The classical Fay's algorithm was implemented with the
      two models to simulate the oil spill trajectory movements. The study shows that
      the slick lengths are effected by tidal current V component with maximum velocity
      of 1.4 m/s. This indicates that oil slick trajectory path is moved towards the
      north direction. The oil slick parcels are accumulated along the coastline after
      48 h. The analysis indicated that tidal current V components were the dominant
      forcing for oil slick spreading.

PMID- 14971451
TI  - Rapid degradation of bensulfuron-methyl upon repeated application in paddy soils.
AB  - Rapid degradation of bensulfuron-methyl upon repeated application in paddy soils
      was studied. The results showed that the DT50 of bensulfuron-methyl was reduced
      from 16 d to 9 d in soil with one-year bensulfuron-methyl application. Rapid
      bensulfuron-methyl degradation was happened to previously untreated soil by
      addition 5% rapid bensulfuron-methyl adapted soil and was inhibited following pre
      treatment with broad-spectrum antibiotic chloramphenicol. In bensulfuron-methyl
      adapted soil mineralisation of 14C labeled bensulfuronmethyl to 14CO2 occurred at
      a faster rate than with previously untreated soil. It was concluded that rapid
      bensulfuron-methyl degradation upon repeated application is probably linked to
      the adaptation of soil bacteria which can utilize bensulfuron-methyl as a source
      of carbon and energy.

PMID- 14971452
TI  - Gas phase trichloroethylene removal at low concentration using activated carbon
      fiber.
AB  - The breakthrough adsorption behaviors of gas phase trichloroethylene in a packed
      bed of activated carbon fibers (ACF) were investigated. The specific surface area
      of the ACF was 600 m2/g, 1400 m2/g and 1600 m2/g, respectively, and the
      concentration of trichloroethylene ranged from 270 mg/m3 to 2700 mg/m3. Results
      showed that the capacity of adsorption increased with increasing specific surface
      area, the relationship between the logarithms of 10% breakthrough time and
      concentration was approximately linear over the experimental range, the
      breakthrough time decreased with increasing temperature and humidity. The
      breakthrough curves at different inlet concentration or different temperature can
      be predicted by several simple theoretical models with good agreements.

PMID- 14971453
TI  - Surface microlayer enrichment of volatile organic compounds and semi-volatile
      organic compounds in drinking water source.
AB  - Enrichment of volatile organic compounds(VOC) and semi-volatility organic
      compounds(SVOC) in surface microlayer(SM) of three drinking water sources were
      studied. The enrichment factor(EFs) were 0.67 to 13.37 and 0.16 to 136,
      respectively. The results showed some VOC and most SVOC could enrich in SM. Some
      EFs of SVOC was quite high. Suspension and temperature could affect EFs of SVOC,
      slim wind and water movement do not destroy enrichment of organic in SM.

PMID- 14971454
TI  - Benzene and lead exposure assessment among occupational bus drivers in Bangkok
      traffic.
AB  - Four environmental and biological monitoring sites were strategically established
      to evaluate benzene and lead exposure assessment at various traffic zones of
      Bangkok Metropolitan Region(BMR). Biological measurement of 48 non air
      conditioned, male bus drivers was carried to study the relationship between
      individual exposure levels and exposure biomarkers. The study group was further
      subdivided into four age groups(16-25, 26-35, 36-45 and 46-55 years old) to
      monitor the age-related exposure effects. A total of 12 unexposed persons were
      deliberately chosen as the control group. Measurement of unmetobolized benzene in
      blood and analysis of urinary tt-Muconic acid urine and urinary creatinine are
      recommended as biomarkers of benzene exposure. Measurement of lead in blood and
      urine is also recommended for the biological monitoring of lead exposure. During
      the monitoring period, benzene and lead levels at Yaowarat Road was C6H6: 42.46
      +/- 3.88 microg/m3 , Pb: 0.29 +/- 0.03 microg/m3 and decreased to C6H6: 33.5 +/-
      1.35 microg/m3, Pb: 0.13 +/- 0.01 microg/m3 at Phahonyothin Road. Significant
      difference was established between the nonsmoking exposed group and nonsmoking
      control group for blood benzene concentrations (P < 0.001, two-tailed, Mann
      Whiteney U test). Strong correlations were also found between trans-trans-Muconic
      acid concentrations in post shift samples and atmospheric benzene concentrations.
      Similarly, good correlation between all of biomarkers and lead level in air is
      established from automobile emissions. The analysis revealed that among the
      occupational population in the urban sites, the driver groups were found to have
      the highest risk of benzene and lead exposures derived from automobile emission.

PMID- 14971455
TI  - Determination of operational parameters of anaerobic phase for enhanced
      phosphorus removal in MBR.
AB  - Two runs of experiments were carried out to obtain an understanding of phosphorus
      release and uptake under the anaerobic condition and then the aerobic condition
      respectively. Under anaerobic condition, it was found that the extent of
      phosphorus release appeared to increase with the increase of the initial organic
      loading rate when the initial organic loading rate was up to 0.1 gSCOD/gMLSS.
      When the initial organic loading rate was higher than 0.1 gSCOD/gMLSS, the amount
      of phosphorus release per unit mass of MLSS reached nearly a same stationary
      value, and it seemed this is not affected by organic loading rate when there is
      external available substrate remained. In addition, the effect of NOx-N on the
      phosphorus release and uptake was also investigated, it was proved that the
      denitrifiers has an advantage over polyphosphate accumulating bacteria in
      competition for organic substrate under anoxic condition. Therefore, the
      existence of NOx-N is disadvantageous to the phosphorus release. Based upon the
      above investigations, the process configuration of membrane bioreactor(MBR) in
      combination with anaerobic phase was proposed to enhance the removal of
      phosphorus in treating domestic wastewater. During the experimental period of
      four months, average removals of 92.50%, 84.25%, 100%, 94.09% and 85.33% were
      achieved for COD, TP, SS, NH3-N and TN respectively.

PMID- 14971456
TI  - Identification of the bound residue composition derived from 14C-labeled
      chlorsulfuron in soil by using LC-MS and isotope tracing method.
AB  - A new method for extracting the bound residue(BR) derived from 14C-labeled
      chlorsulfuron in soils was developed, and the technique of combining LC-MS with
      isotope tracing method was subsequently applied to identify the composition of
      the 14C-BR in a loamy Fluvent derived from marine deposit. The results showed
      that the 14C-[2-amino-4-methoxyl-6-methyl-1,3,5]-triazine, 14C-[2-amino-4
      hydroxyl-6-methyl-1,3,5]-triazine and 14C-chlorsulfuron parent compound
      constituted the main composition of the 14C-BR derived from 14C-labeled
      chlorsulfuron in the soil. The radioactive ratio of three compounds accounted for
      39.8%, 35.4% and 17.9% of total recovered radioactivity, respectively. However, a
      small amount(3.6% of total recovered radioactivity) of the complex of 14C-[2
      amino-4-hydroxyl-6-methyl-1,3,5]-triazine might have existed in the 14C-BR in
      association with an unknown soil substrate. 2-chlorobenzenesulfonamide was also
      detected to be one of the components of the BR. The results could well explain
      the mechanism of phytotoxicity caused by the BR derived from chlorsulfuron in
      soil. In addition, the mechanism of BR formation in soil was also discussed in
      details.

PMID- 14971457
TI  - Lead adsorption capacities of different components in natural surface coatings.
AB  - Pb adsorption capacities of Fe oxide, Mn oxide and organic materials in natural
      surface coatings( biofilms and associated minerals) collected in three lakes, two
      ponds and a river in Jilin Province, China and Cayuga Lake in US were studied. A
      novel extraction technique was employed to remove one or more component(s) from
      the surface coatings. Pb adsorption to surface coatings before and after
      extraction was performed to determine the adsorptive properties of the extracted
      component(s). The statistical analysis of observed Pb adsorption was carried out
      using nonlinear least squares fitting(NLSF) to estimate the Pb adsorption
      capacity of each component of surface coatings. For each body of water, the
      estimated Pb adsorption capacity of Mn oxide(mol Pb/mol Mn) was significantly
      higher than that of Fe oxide(mol Pb/ mol Fe). The value of estimated adsorption
      capacities of organic materials with the unit mol Pb per kg COD was similar to or
      less than that of Fe oxides with the unit mol Pb per mol Fe. Comparison of
      components of surface coatings in different waters showed that the estimated Pb
      adsorption capacities of components in surface coatings developed in different
      natural waters were different, especially for Mn oxides.

PMID- 14971458
TI  - An estimate on the rainout of atmospheric CO2.
AB  - The CO2 in the atmosphere is in contact with water vapor and rain droplets
      forming CO2 x H2O, HCO3- and CO3(2-) . Global precipitation is about 505 x 1015
      kg/a. Based on theoretical calculation for unpolluted air and measurement
      observations, we estimated that 100-270 x 10(12) gC/a are scavenged from the air
      by global precipitation. This roughly equals carbon emissions from volcanic
      sources or 2-6 per cent of current CO2 emissions. An inventory-based estimate on
      carbon removal in northwestern Europe supports the above calculation on global
      scale. With increasing CO2 concentration in the air, precipitation scavenging may
      increase.

PMID- 14971459
TI  - Using a zeolite medium biofilter to remove organic pollutant and ammonia
      simultaneously.
AB  - A pilot scale zeolite medium biological aerated filter(ZBAF) was designed and
      used to treat municipal wastewater. It showed that ZBAF could simultaneously
      remove chemical oxygen demand(COD), ammonia-N and turbidity to satisfied degree
      at a hydraulic retention time(HRT) of 0.95 h. Their average removal efficiencies
      were 73.9%, 88.4% and 96.2% with the corresponding average effluent
      concentrations of 43.4 mg/L, 3.5 mg/L and 3.7 NTU, respectively. These effluent
      items met with the water quality standard of the treated water reused for cooling
      water. The COD removal volumetric loading rate increased proportionally with its
      applied volumetric loading rate with its maximum of 7.1 kg/(m3 x d). Ammonia-N
      removal loading rate also increased proportionally with its applied loading rate
      at HRT of longer than 0.95 h and the feasible maximum removal loading rate was
      0.9 kg/(m3 x d). The COD loading rate did not affect the ammonia-N removal
      efficiency significantly when it was lower than 5.5 kg/(m3 x d). ZBAF has good
      application prospect for its low cost and high removal efficiency in the future.

PMID- 14971460
TI  - Neutron activation analysis of ceramic tiles and its component and radon
      exhalation rate.
AB  - The concentrations of 20 trace elements in several ceramics tiles and ceramic
      composites used in Egypt were elementally analyzed by neutron activation
      analysis(NAA) technique. The samples and standard were irradiated with reactor
      for 4 h (in the Second Research Egyptian Reactor(Et-RR-2)) with thermal neutron
      flux 5.9 x 10(13) n/(cm2 x s). The gamma-ray spectra obtained were measured for
      several times by means of the hyper pure germanium detection system(HPGe). Also a
      solid state nuclear track detector(SSNTD) CR-39, was used to measure the
      emanation rate of radon for these samples. The radium concentrations were found
      to vary from 0.39-3.59 ppm and the emanation rates were found to vary from (0.728
      5.688) x 10(-4) kg/(m2 x s). The elemental analysis of the ceramic tiles and
      ceramic composites have a great importance in assigning the physical properties
      and in turn the quality of the material.

PMID- 14971461
TI  - Life cycle assessment of mobile phone housing.
AB  - The life cycle assessment of the mobile phone housing in Motorola(China)
      Electronics Ltd. was carried out, in which materials flows and environmental
      emissions based on a basic production scheme were analyzed and assessed. In the
      manufacturing stage, such primary processes as polycarbonate molding and surface
      painting are included, whereas different surface finishing technologies like
      normal painting, electroplate, IMD and VDM etc. were assessed. The results showed
      that housing decoration plays a significant role within the housing life cycle.
      The most significant environmental impact from housing production is the
      photochemical ozone formation potential. Environmental impacts of different
      decoration techniques varied widely, for example, the electroplating technique is
      more environmentally friendly than VDM. VDM consumes much more energy and raw
      material. In addition, the results of two alternative scenarios of
      dematerialization showed that material flow analysis and assessment is very
      important and valuable in selecting an environmentally friendly process.

PMID- 14971462
TI  - Bubble performance of a novel dissolved air flotation(DAF) unit.
AB  - ES-DAF, a novel DAF with low cost, high reliability and easy controllability, was
      studied. Without a costly air saturator, ES-DAF consists of an ejector and a
      static mixer between the pressure side and suction side of the recycle rotary
      pump. The bubble size distribution in this novel unit was studied in detail by
      using a newly developed CCD imagination through a microscope. Compared with M-DAF
      under the same saturation pressure, ES-DAF can produce smaller bubble size and
      higher bubble volume concentration, especially in lower pressure. In addition,
      the bubble size decreases with the increase of reflux ratio or decrease of
      superficial air-water ratio. These results suggested that smaller bubbles will be
      formed when the initial number of nucleation sites increases by enhancing the
      turbulence intensity in the saturation system.

PMID- 14971463
TI  - ORC-GAC-Fe0 system for the remediation of trichloroethylene and monochlorobenzene
      contaminated aquifer: 1. Adsorption and degradation.
AB  - Activities at a former Chemistry Triangle in Bitterfeld, Germany, resulted in
      contamination of groundwater with a mixture of trichloroethylene(TCE) and
      monochlorobenzene(MCB). The objective of this study was to develop a barrier
      system, which includes an ORC(oxygen release compounds) and GAC(granular
      activated carbon) layer for adsorption of MCB and bioregeneration of GAC, a Fe0
      layer for chemical reductive dechlorination of TCE and other chlorinated
      hydrocarbon in situ. A laboratory-scale column experiment was conducted to
      evaluate the feasibility of this proposed system. This experiment was performed
      using a series of continuous flow Teflon columns including an ORC column, a GAC
      column, and a Fe0 column. Simulated MCB and TCE contaminated groundwater was
      pumped upflow into this system at a flow rate of 1.1 ml/min. Results showed that
      17%-50% of TCE and 28%-50% of MCB were dissipated in ORC column. Chloride ion,
      however, was not released, which suggest the dechlorination do not happen in ORC
      column. In GAC column, the adsorption of contaminants on activated carbon and
      their induced degradation by adapted microorganisms attached to the carbon
      surface were observed. Due to competitive exchange processes, TCE can be desorbed
      by MCB in GAC column and further degraded in iron column. The completely
      dechlorination rate of TCE was 0.16-0.18 cm(-1), 1-4 magnitudes more than the
      formation rate of three dichloroethene isomers. Cis-DCE is the main chlorinated
      product, which can be cumulated in the system, not only depending on the
      formation rate and its decaying rate, but also the initial concentration of TCE.

PMID- 14971464
TI  - Management of process performance at low water temperatures in respect of
      filamentous organisms.
AB  - The management of sludge-settling properties in Nordic conditions is of
      importance during the low temperature (spring) season because of the peak settler
      load. A survey was made in 10 Finnish waste water treatment plants (WWTP's) and
      the total extended filament length and DSVI in half of the plants exceeded the
      limits, which indicates sludge bulking (15 km/g SS and 150 ml/g respectively).
      The dominant organism was Microthrix parvicella, the abundance of which was
      59.22% of total extended filament length on average. Chemicals were tested to
      control the filaments, and it was found that special attention has to be paid to
      maintaining the nitrification at low temperature. A dosage of (H2O2-based)
      oxidants controlled the growth of Microthrix parvicella effectively and rapidly,
      whereas with the use of aluminium hydroxidechloride a 2 to 5-week period was
      needed to decrease the filament length.

PMID- 14971465
TI  - Preparation and characterization of mixed hydroxy-Fe-Al pillared montmorillonite
      with large basal spacing.
AB  - Mixed hydroxy-Al-Fe pillared montmorillonites with large basal spacing were
      successfully prepared through cation-exchanging of Na+ - montmorillonite with
      mixed hydroxy-Al and hydroxy-Fe pillaring solutions made from hydrolysis of
      corresponding metal salts, followed by calcination to convert hydroxy-Al and
      hydroxy-Fe into intercalated polycations. According to XRD analysis, the basal
      spacing d(001) of pillared products dramatically enlarged from 12.7 A in the Na
      montmorillonite to 81 A in the hydroxy-Fe -montmorillonite and 77.5 A in mixed
      hydroxy-Al-Fe-montmorillonite. The N2 BET surface areas of the pillared
      montmorillonites also greatly increased to more than 200 m2/g as compared to
      about 27 m2/g for the Na-montmorillonite. IR analysis of hydroxy-Fe, and mixed
      hydroxy-Al-Fe pillared montmorillonites revealed a new absorption vibration at
      1384 cm(-1) wavelength. XRF elemental analysis data also showed a high content of
      Fe2O3 in the hydroxy-Fe pillared montmorillonite.

PMID- 14971466
TI  - A grey multi-objective programming approach for sustainable land-use in the Miyun
      Reservoir basin, China.
AB  - Miyun Reservoir is the most important water source to Beijing City. Land-use of
      the basin plays a great role in the protection of water resources. Hence a
      sustainable land-use planning is required to optimize land-use structure and
      protect water resources in the basin. Based on the complete land-use system
      analysis in Miyun, a grey multi-objective programming to basin land-use(GMOPBLU)
      model was developed and applied to land-use planning. Two alternatives were
      produced and analyzed by means of interactive adjustment and scenario analysis.
      The results showed the GMOPBLU model is a valuable approach for basin land-use
      planning.

PMID- 14971467
TI  - Optimum municipal wastewater treatment plant design with consideration of
      uncertainty.
AB  - A newly developed model for the optimum municipal wastewater treatment plant
      (MWTP) design is presented. Through introducing the interval variables, the model
      attempts to consider the effects of uncertainties caused by the fluctuation of
      the wastewater quality and quantity during the design of MWTP. The model solution
      procedure is illustrated in detail, and a numerical example is given to verify
      the feasibility and advantage of the model. Furthermore, the possibility of the
      model application is briefly outlined.

PMID- 14971468
TI  - Evaluation of fungal potentiality for bioconversion of domestic wastewater
      sludge.
AB  - This study was undertaken to screen the filamentous fungi isolated from its
      relevant habitats(wastewater, sewage sludge and sludge cake) for the
      bioconversion of domestic wastewater sludge. A total of 35 fungal strains were
      tested against wastewater sludge (total suspended solids, TSS 1%-5% w/w) to
      evaluate its potentiality for enhancing the biodegradability and dewaterability
      using liquid state bioconversion(LSB) process. The strains were divided into five
      groups i.e. Penicillium, Aspergillus, Trichoderma, Basidiomycete and
      Miscellaneous, respectively. The strains WWZP1003, SCahmA103, SCahmT105 and PC-9
      among their respective groups of Penicillium, Aspergillus, Trichoderma and
      Basidiomycete played potential roles in terms of separation (formation of
      pellets/flocs/filaments), biodegradation(removal of COD) and filtration
      (filterability) of treated domestic wastewater sludge. The Miscellaneous group
      was not considered due to its unsatisfactory results as compared to the other
      groups. The pH value was also influenced by the microbial treatment during
      fermentation process. The filterability of treated sludge was improved by fungal
      treatment, and lowest filtration time was recorded for the strain WWZP1003 and
      SCahmA103 of Penicillium and Aspergillus groups respectively compared with other
      strains.

PMID- 14971469
TI  - Residential environmental evaluation of local cities considering regional
      characteristic and personal residential preference-a case study of Saga City,
      Japan.
AB  - Questionnaire surveys and subjective evaluations on residential environment were
      performed in order to grasp the main factors of residential environment of small
      local cities. The suitable evaluation index system was established, and the
      regional residential environment characteristics and personal residential
      preference types were analyzed, so that their influence on residential
      environment evaluation could be grasped. The results can be applied to the
      residential environment planning, construction and monitoring of local cities.

PMID- 14971470
TI  - OH radicals generated by DC corona discharge for improving the pulsed discharge
      desulfuration efficiency.
AB  - Positive DC corona discharge is formed with needle-plate electrode configuration,
      in which the water vapor is ejected though the needle points. The purpose is to
      increase the numbers of the water-based radicals, ionize the water molecule and
      improve the desulfuration efficiency of pulsed corona reactor. The water ions
      were determined by four stages molecular beam mass spectrometer and diagnose the
      water-based radicals by emission spectrograph. A conclusion on formation of ions
      and radicals with DC corona discharges can be drawn.

PMID- 14971471
TI  - Distribution of endocrine-disrupting PCBs in hard roes of loaches and their
      potential ecological effects in Weishanhu Lake, China.
AB  - Preliminary study is carried out on the endocrine-disrupting organic chemicals of
      polychlorinated biphenyls( PCBs: PCB-28, 60, 104, 153, 190) in hard roes of
      loaches( Misgurnus anguillicaudatas) in Weishanhu Lake, China. Results showed
      that the hard roes of loaches collected from the areas near the influx(such as
      Pengkou T-PCB = 0.243 microg/g) or efflux(such as Hanzhuang T-PCB = 0.221
      microg/g) are characterized by higher PCB contents, about 4 times that from the
      central lake(T-PCB = 0.066 microg/g), suggesting great difference between their
      pollutions. The PCB distributions indicated that PCB congeners with more chlorine
      are more easily accumulated in roes of loaches. The microscopic characteristics
      reveal that the PCB contents at present cannot lead the roes of loaches to be
      abnormal. However, the roes with higher PCBs in Pengkou and Hanzhuang are
      obviously bigger than those with lower PCBs(T-PCBs < or = 0.176 microg/g) in
      other localities. It is suggested that PCBs have a stronger estrogenic activity
      on the roes of loaches, and the phenomenon is likely premonitory for the abnormal
      development of the hard roes.

PMID- 14971472
TI  - Influence of packing media on nitrogen removal in a subsurface infiltration
      system.
AB  - Influence of packing media on nitrogen removal in a subsurface infiltration
      system was studied. System A was filled with loamy soil and system B was filled
      with mixed soil of 75% red clay with 25% cinder. Both systems were fed with
      sewage at the same hydraulic loading of 2 cm/d at continuous operation mode. The
      same excellent removal performances of COD and T-P could be achieved in both
      infiltration systems with removal rates about 85% and 98%, respectively. In
      system A, NH4+ -N removal rate was as high as 96.5% and T-N removal rate was
      relatively much lower as 55.7%. And in system B, NH4+ -N removal rate was as low
      as 75.4% and T-N removal rate was relatively much higher as 75.5% . The
      difference was attributed to different soil oxidation-reduction condition that
      was greatly influenced by soil texture in subsurface infiltration system. Loamy
      soil led to oxidative condition that was favorable to nitrification and
      disadvantageous to denitrification. The results were just adverse to the system
      filled with clay. Intermittent operation was adopted to improve nitrogen removal
      in system B. NH4+ -N removal rate could be increased to about 95% and T-N removal
      rate could be increased to about 90% at intermittent operation mode in system B.
      Analysis of nitrogen removal mechanisms indicated that nitrification
      denitrification was the primary nitrogen removal path in subsurface infiltration
      system and crop uptake was another important nitrogen removal way. It was the key
      to improve the total N removal performance that a suitable packing soil was
      available to present favorable oxidation-reduction condition for simultaneous
      nitrification and denitrification.

PMID- 14971473
TI  - Valuing health effects from the industrial air pollution in rural Tianjin, China.
AB  - High concentrations of air pollutants such as total suspended particulates (TSP)
      and sulfur dioxide (SO2) have serious impacts on nearby populations. In this
      paper, a survey of rural Tianjin residents' willingness-to-pay for health
      improvement was reported on, and the MBDC (multiple bounded discrete choice)
      model was adopted to study the respondents' willingness-to-pay to prevent
      respiratory illnesses. The results showed that the willingness-to-pay for health
      improvement was affected by respondents' health condition, work situation and
      environmental awareness, but not by personal habits, such as smoking. If person's
      willingness-to-pay to avoid respiratory diseases can be considered equal to the
      cost to personal health caused by air pollution, the total cost will reach 538 x
      10(6) RMB Yuan (RMB, equal to 65 million USD) per year.

PMID- 14971474
TI  - Long-term temporal-spatial dynamics of marine coastal water quality in the Tolo
      Harbor, Hong Kong, China.
AB  - The long-term temporal and spatial dynamics of marine coastal water quality in
      Tolo Harbor, Hong Kong were explored. The Harbor is divided into three zones
      represented as Harbor, Buffer, and Channel Subzones. The time range for the study
      covers the period from the 1970s to the 1990s. The selected indicators for the
      comprehensive assessment of water quality consist of physical, chemical and
      biological aspects, including suspended solids(SS), Secchi disk depth(SD), 5-day
      biochemical oxygen demand(BOD5), total nitrogen (TN), total phosphorus(TP),
      faecal coliform, chlorophyll-a(Chl-a), and the number of red tide occurrences.
      The results indicated the presence of obvious temporal and spatial trends with
      regard to changes in water quality. Spatially, water quality in the Channel
      Subzone is the best, while that in the Harbor Subzone is the worst. On a temporal
      basis, the average trend from bad to good was 1980s > 1990s > 1970s as indicated
      by most of the selected water quality indicators. Water quality during the late
      1980s reached its worst level with the lowest SD, the highest BOD5, TN, TP, Chl-a
      concentrations, and the number of red tide occurrences. These long-term temporal
      spatial water quality trends were also found in other studies of the Tolo Harbor.
      The large quantity of pollutants produced as a result of increasing population,
      industrial and commercial actives, and urbanization and industrialization trends
      in both Shatin and Tai Po seem to be primarily responsible for the changes in
      marine coastal water quality.

PMID- 14971475
TI  - Ecological footprint of Shandong, China.
AB  - Ecological footprint has been given much attention and widely praised as an
      effective heuristic and pedagogic device for presenting current total human
      resource use in a way that communicates easily to almost everyone since 1996 when
      Wackernagel and Rees proposed it as a sustainable development indicator.
      Ecological footprint has been improving on its calculation and still can be a
      benchmark to measure sustainable development although there are still ongoing
      debates about specific methods for calculating the ecological footprint. This
      paper calculates the ecological footprint of Shandong Province, China with the
      methodology developed by Wackernagel and analyzes the current situation of
      sustainable development in Shandong.

PMID- 14971476
TI  - Effects of temperature on UV-B-induced DNA damage and photorepair in Arabidopsis
      thaliana.
AB  - DNA damage in the form of cyclobutane pyrimidine dimers(CPDs) and (6-4)
      photoproducts(6-4PPs) induced by UV-B radiation in Arabidopsis thaliana at
      different temperatures was investigated using ELISA with specific monoclonal
      antibodies. CPDs and 6-4PPs increased during 3 h UV-B exposure, but further
      exposure led to decreases. Contrary to the commonly accepted view that DNA damage
      induced by UV-B radiation is temperature-independent because of its photochemical
      nature, we found UV-B-induction of CPDs and 6-4PPs in Arabidopsis to be slower at
      a low than at a high temperature. Photorepair of CPDs at 24 degrees C was much
      faster than that at 0 degrees C and 12 degrees C, with 50% CPDs removal during 1
      h exposure to white light. Photorepair of 6-4PPs at 12 degrees C was very slow as
      compared with that at 24 degrees C, and almost no removal of 6-4PPs was detected
      after 4 h exposure to white light at 0 degrees C. There was evidence to suggest
      that temperature-dependent DNA damage and photorepair could have important
      ecological implications.

PMID- 14971477
TI  - Flow-switching device for comprehensive two-dimensional gas chromatography.
AB  - A simple flow-switching device has been developed as a differential flow
      modulator for comprehensive two-dimensional gas chromatography (GC x GC). The
      device is assembled from tubing, four tee unions, and a solenoid valve. The
      solenoid valve is located outside the oven of the gas chromatograph and is not in
      the sample path. The modulation technique has no inherent temperature
      restrictions and passes 100% of the primary column effluent to the secondary
      column(s). Secondary peaks are produced with widths at half maximum less than 100
      ms when operating in GC x 2GC mode with a 2.0 s modulation period. The efficacy
      of this approach is demonstrated through the analysis of a standard mixture of
      volatile organic compounds (VOCs) and diesel fuel.

PMID- 14971478
TI  - Validation of a laboratory-constructed automated gas chromatograph for the
      measurement of ozone precursors through comparison with a commercial analogy.
AB  - An automated gas chromatographic (auto-GC) system aiming at performing unattended
      hourly measurement of ozone precursors was developed in the laboratory. To
      encompass volatile organic compounds (VOCs) of a wide range of volatility within
      each analysis, the system uses dual-traps and dual-columns to simultaneously
      analyze both low and high-boiling compounds with each injection. Since sorbents
      with sufficient retention of C2 compounds at room temperature, namely ethane,
      ethene, and ethyne are not yet available, cooling with a thermoelectrical device
      was built around the low-boiling trap to facilitate quantitative enrichment of C2
      compounds. The effectiveness of using micro-trap with low dead volume plumbing
      was manifested in reducing peak width and increasing peak height for particularly
      the lower-boiling compounds. The increase in sensitivity allowed sufficient
      detector response with a small amount of air sample, e.g. 200 ml in our routine
      operation, which in term eliminate the need for remove water prior to sampling
      trapping. The performance and applicability of this laboratory-built auto-GC
      system was validated by comparison with a commercial analog, i.e. the ATD-400
      system made by Perkin-Elmer, in the field sharing a common air intake. During
      more than 3 weeks of synchronized monitoring of ambient volatile organic
      compounds both systems showed highly consistent results on almost every monitored
      compound, clearly demonstrating the robustness of this self-built system.

PMID- 14971479
TI  - Evaluation of the pulsed discharge helium ionization detector for the analysis of
      hydrogen and methane in breath.
AB  - Under the appropriate separation conditions the pulsed discharge helium
      ionization detector (PDHID) was used to detect hydrogen and methane separated
      from the matrix components of human breath samples. The sensitivity of this
      method is over an order of magnitude better than published methods using a flame
      ionization detector (FID) and a thermal conductivity detector (TCD), and has the
      further advantage of detecting both analytes with only one detector. Limits of
      detection were 0.3 ppmv for both hydrogen and methane and the method had a linear
      dynamic range (LDR) of three orders of magnitude (0.3-400 ppm, v/v). The PDHID
      was also compared to the FID and the TCD in regard to selectivity, sensitivity
      and reproducibility for high-speed gas chromatography (HSGC). It was shown that
      the PDHID is as sensitive as the FID for fast separations but is limited by the
      difficulty of resolving analyte peaks from O2 and N2. The PDHID was at least
      three orders of magnitude more sensitive than the TCD for all of the analytes
      examined.

PMID- 14971480
TI  - Gas chromatography-mass spectrometry of carbonyl compounds in cigarette
      mainstream smoke after derivatization with 2,4-dinitrophenylhydrazine.
AB  - An improved gas chromatography-mass spectrometry (GC-MS) method was described for
      the analysis of carbonyl compounds in cigarette mainstream smoke (CMS) after 2,4
      dinitrophenylhydrazine (DNPH) derivatization. Besides formaldehyde, acetaldehyde,
      acetone, acrolein, propionaldehyde, methyl ethyl ketone, butyraldehyde, and
      crotonaldehyde that are routinely analyzed in cigarette smoke, this technique
      separates and allows the analysis of several C4, C5 and C6 isomeric carbonyl
      compounds. Differentiation could be made between the linear and branched carbon
      chain components. In cigarette smoke, the branched chain carbonyls are found at
      higher level than the linear chain carbonyls. Also, several trace carbonyl
      compounds such as methoxyacetaldehyde were found for the first time in cigarette
      smoke. For the analysis, cigarette smoke was collected using DNPH-treated pads,
      which is a simpler procedure compared to conventional impinger collection.
      Thermal decomposition of DNPH-carbonyl compounds was minimized by the
      optimization of the GC conditions. The linear range of the method was
      significantly improved by using a standard mixture of DNPH-carbonyl compounds
      instead of individual compounds for calibration. The minimum detectable quantity
      for the carbonyls ranged from 1.4 to 5.6 microg/cigarette.

PMID- 14971481
TI  - Quantitative analysis of benzene, toluene, and xylenes in urine by means of
      headspace solid-phase microextraction.
AB  - A simple method for benzene, toluene, and xylenes (BTX) quantitative analyses in
      human urine was developed, using headspace solid-phase microextraction (HS-SPME)
      and gas chromatography coupled to mass spectrometry detection in the single ion
      monitoring mode. The developed method is solventless, non-invasive, requires
      small volume of sample (1 ml), shows high selectivity, sensitivity,
      repeatability, and linearity (correlation coefficients >0.998), providing a
      useful alternative to assess human exposure to BTX compounds due to occupational
      reasons or eventual exposure to organic solvents. Detection limit varies from
      0.28 to 0.5 ppb (v/v).

PMID- 14971482
TI  - Construction and validation of an automated spray-and-trap gas chromatograph for
      the determination of volatile organic compounds in aqueous samples.
AB  - An automated spray-and-trap (ST) chromatographic system was constructed for fast
      and efficient extraction of volatile organic compounds (VOCs) in aqueous samples
      with the capability to be deployed in the field for unattended continuous
      monitoring of surface or ground water. This system was built upon a commercial
      gas chromatograph with full automation capability using self-developed hardware
      and software. For sample analysis, fine droplets of the aqueous solution were
      generated in the extraction chamber by pressure expansion of a clean air stream
      through a spray nozzle. A portion of the VOCs distributed into the gas phase was
      retained by a multi-sorbent micro-trap kept at ambient temperature. Flash heating
      of the sorbent trap desorbed the enriched VOCs onto the gas chromatography (GC)
      with flame ionization detection (FID) for hydrocarbons or electron-capture
      detection (ECD) for halocarbons. In order to validate the performance of the ST
      method. it was compared with a more conventional method, i.e., a purge-and-trap
      (PT), by analyzing a serious of standard solutions containing benzene, toluene,
      ethylene. and o-, m-xylenes. Using a purge-and-trap method as a reference for
      complete extraction, the ST method showed less sensitivity. Extraction recoveries
      are in consistent with Henry's law constants. To test response time the ST-GC-ECD
      was periodically switched between tap and underground waters. Negligible carry
      over of halogenated species and reproducibility better than 2% relative standard
      deviation (R.S.D.) can be achieved regardless of large concentration difference
      between the two sources, thus demonstrating applicability of the ST system for on
      site monitoring.

PMID- 14971483
TI  - Fast chromatographic determination of polycyclic aromatic hydrocarbons in aerosol
      samples from sugar cane burning.
AB  - Sugar cane burning in Brazil causes remarkable amounts of organic compounds to be
      emitted amongst which the polycyclic aromatic hydrocarbons (PAHs) represent
      serious health hazards. Therefore, 24-h aerosol samples (< 10 microm aerodynamic
      diameter) were collected in Araraquara city (Sao Paulo state) during the harvest
      season using a Hi-Vol sampler. PAHs were recovered using an Accelerated Solvent
      Extractor and analyzed by low-pressure gas chromatography-ion trap mass
      spectrometry (LP-GC-IT-MS). The fully automated extraction process was performed
      in less than 25 min with a solvent consumption of approximately 20 ml. The use of
      a deactivated 0.6 m x 0.10 mm i.d. restrictor coupled to a 10 m wide-bore
      analytical column allowed most of the 16 PAHs in EPA's priority list to be
      identified and quantified in only 13 min. Concentrations of PAHs in Araraquara
      aerosols ranged between 0.5 and 8.6 ng m(-3).

PMID- 14971484
TI  - Application of a system suitability test for quality assurance and performance
      optimisation of a gas chromatographic system for pesticide residue analysis.
AB  - In pesticide residue analysis, screening for over 150 compounds has to be
      performed on a daily basis. As part of the quality control measures it is crucial
      to verify that the chromatographic system fits the purpose, or if any
      deterioration occurred during its previous use. The operation conditions of the
      chromatographic system can be best monitored with properly selected system
      suitability test (SST) mixtures, which provide information with one injection on
      the characteristic performance parameters of the whole system from the injector
      to the detectors. We developed SST mixtures that are also suitable for use with
      electron-capture, nitrogen-phosphorus and pulse flame photometric detectors.
      These SST mixtures were applied over 3 years to monitor the system performance
      parameters, such as the number of effective theoretical plates, resolution,
      asymmetry, detection limit and selectivity. The applicability and advantages of
      these tests are illustrated and discussed.

PMID- 14971485
TI  - Trace determination of bisphenol A and phytoestrogens in infant formula powders
      by gas chromatography-mass spectrometry.
AB  - This investigation describes a reliable and sensitive method for simultaneously
      determining bisphenol A (BPA) and two major phytoestrogens, daidzein and
      genistein, in powdered milks and infant formulas by gas chromatography-mass
      spectrometric analysis after trimethylsilylation. To reduce the matrix
      interference associated with the constituents of the formulas, the dissolved
      formula solutions were firstly ultra-centrifuged and the analytes in the
      supernatant were then extracted using a C18 solid-phase extraction column. The
      accuracy and precision of the method were determined and the technique was
      successfully employed to measure trace concentrations of BPA, daidzein and
      genistein in powdered formulas. The results show that BPA, daidzein and genistein
      were detected in all the testing samples (n = 6) at concentrations from 45 to 113
      ng/g (except one infant formula), 20 to 2050 ng/g and 21 to 6510 ng/g,
      respectively. The highest concentrations of daidzein and genistein (i.e., 2050
      and 6510 ng/g) were detected in a soy-based powdered infant formula. The
      quantitation limits were 1.0 ng/g for BPA, and 10 ng/g for daidzein and genistein
      using 0.5 g powdered milk samples.

PMID- 14971486
TI  - High-speed analysis of residual solvents by flow-modulation gas chromatography.
AB  - High-speed gas chromatographic (GC) separation of residual solvents in
      pharmaceutical preparations, using a flow-modulation technique, is described.
      These volatile compounds are separated on a series-coupled (tandem) column
      ensemble consisting of a polyethylene glycol column and a
      trifluoropropylmethyl/dimethylpolysiloxane column. This column ensemble is
      operated in stop-flow mode to enhance, or "tune", the separation. A valve between
      the junction point of the tandem column ensemble and a source of carrier gas at a
      pressure above the GC inlet pressure is opened for intervals of 2-8 s. This stops
      or slightly reverses the flow of carrier gas in the first column. Stop-flow
      pulses are used to increase the separation of target analytes that overlap in the
      total ensemble chromatogram, compared to non-stop-flow, or conventional,
      operation. All 36 target compounds, based on ICH Classes I and II residual
      solvent lists, are resolved in 12 min using the stop-flow technique and a single
      chromatographic analysis.

PMID- 14971487
TI  - Analysis of organic volatile impurities in pharmaceutical excipients by static
      headspace capillary gas chromatography.
AB  - A systematic approach for the identification and quantification of organic
      volatile impurities (OVIs) in pharmaceutical excipients is described. Analytical
      procedures utilizing static headspace capillary gas chromatography coupled with
      flame-ionization and MS detection techniques were developed for the analysis of
      toxic ICH class 1 solvents and US Pharmacopeia OVIs at sub-ppm levels, and
      commonly used organic solvents in a wide range of concentrations. Chromatographic
      conditions and headspace parameters for the methods were optimized for
      separation, sensitivity, and speed. The proposed methodologies were demonstrated
      to be selective, accurate, and reproducible, and were successfully applied to the
      rapid screening of OVIs in typical excipients.

PMID- 14971488
TI  - Complementary use of gas chromatography-mass spectrometry, gas chromatography
      atomic emission detection and nuclear magnetic resonance for identification of
      pharmaceutically related impurities of unknown structures.
AB  - The complementary use of gas chromatography-mass spectrometry (GC-MS), gas
      chromatography-atomic emission detection (GC-AED) and nuclear magnetic resonance
      (NMR) spectroscopy is demonstrated by the identification of four major by
      products in a sample from an exploratory attempt to synthesise 1.3-dichloro-5
      (difluoromethoxy)benzene. GC-MS was used for straightforward identification of
      the target compound and one of the impurities. By employing GC-AED, the sample
      was screened for heteroatoms in the analysed molecules and determination of the
      partial empirical formula of one sample component was carried out. The combined
      spectroscopic data obtained from the MS and AED experiments facilitated structure
      elucidation of two of the additional by-products. Finally, identification of the
      last unknown component could be obtained by combining spectral information from
      GC-MS, GC-AED and NMR data acquired after isolation of the impurity from the
      sample.

PMID- 14971489
TI  - Determination of alkyltrimethylammonium surfactants in hair conditioners and
      fabric softeners by gas chromatography-mass spectrometry with electron-impact and
      chemical ionization.
AB  - The commercial hair conditioners and fabric softeners were analyzed for the
      content of alkyltrimethylammonium compounds (ATMACs) by gas chromatography-mass
      spectrometry (GC-MS) with electron impact (EI) and low-pressure positive-ion
      chemical ionization (PICI) modes. The method involves mixed diluted samples
      (adjust pH to 10.0) with potassium iodide to enhance the extraction of iodide
      ATMA+ ion pairs by direct liquid-liquid extraction. The iodide-ATMA+ pairs were
      then demethylated to their corresponding nonionic alkyldimethylamines (ADMAs) by
      thermal decomposition in a GC injection-port. A high abundance of ADMAs was
      detected at the temperature above 300 degrees C in the GC injection-port. The
      enhanced selectivity of quasi-molecular ion chromatograms of C12-C18-ADMA,
      obtained using methanol PICI-MS enables ADMAs to be identified. The accuracy and
      precision of the method was validated and was successfully applied to determine
      contents of ATMAC in commercial hair conditioners and fabric softeners. The
      contents of total measured ATMAC ranged from 0.4 to 6.9% for hair conditioners,
      and from 3.3 to 4.6% for fabric softeners.

PMID- 14971490
TI  - Quantitation of suspected allergens in fragrances part II. Evaluation of
      comprehensive gas chromatography-conventional mass spectrometry.
AB  - The European legislation requires that fragranced products are evaluated for
      their content in 24 compounds that are suspected to be skin sensitizers. Their
      quantitation in fragrance concentrates may not be achieved with GC-flame
      ionization detection (FID), due to the complexity of these mixtures and even
      comprehensive GC-FID does not provide sufficient resolution. This paper reports
      the first example of quantitation based on the hyphenation of comprehensive GC
      with a low-cost quadrupole MS. A detection frequency of 30.7 Hz can be obtained
      by monitoring a single ion. This allows a satisfactory evaluation of the area sum
      over the 2-3 modulations of a given compound and linear calibration curves are
      obtained. Analyses are completed within 35 min.

PMID- 14971491
TI  - Optimization of carbohydrate silylation for gas chromatography.
AB  - We developed and optimized a new carbohydrate mono- and disaccharides silylation
      reaction, replacing pyridine and requiring lower reaction temperature and less
      time. Our method consists of three basic steps. The first one is oxime formation,
      the second one silylate derivative and the last one gas chromatography separation
      and quantification with an internal standard. We evaluated several solvents,
      including acetonitrile, hydroxylamine and aniline. We found aniline to be the
      best reaction media for oxime formation with hydroxylamine hydrochloride. Among
      silylation agents we found N,O-bis(trimethyl)trifluoroacetamide (BSTFA) was the
      most efficient. Together these reagents favored both a short analysis time and
      fewer by-products. We evaluated the method with model solutions containing:
      arabinose and co-eluting xylose, fructose, glucose, sucrose and salicin (internal
      standard) and found it suitable for processed food analysis.

PMID- 14971492
TI  - Capillary gas chromatography-mass spectrometry of volatile and semi-volatile
      compounds of Salvia officinalis.
AB  - The essential oil and infusion of Salvia officinalis leaves have been widely
      applied in traditional medicine since ancient times and nowadays subjected to
      extensive research of their antibacterial, antiviral and cytotoxic properties.
      This paper shows chemical composition data of S. officinalis leaves essential oil
      isolated by steam distillation using a Clevenger-type apparatus. Also, the paper
      presents the chemical content of volatile and semi-volatile compounds of S.
      officinalis leaves infusion. The volatile and semi-volatile compounds of S.
      officinalis leaves infusion were isolated by solid-phase extraction (SPE) and
      liquid-liquid extraction with hexane and dichloromethane. SPE was carried out on
      500 mg octadecylsilane (C18) cartridges and elution with dichloromethane. Liquid
      liquid extraction was performed with hexane and dichloromethane. The essential
      oil in dichloromethane and infusion extracts in hexane and dichloromethane were
      analyzed by gas chromatography coupled with mass spectrometry. The quantitative
      results obtained by solid-phase extraction and liquid-liquid extraction showed
      that SPE on C18 performed the highest recovery of the volatile compounds from
      infusion sample.

PMID- 14971493
TI  - Application of low-pressure gas chromatography-ion-trap mass spectrometry to the
      analysis of the essential oil of Turnera diffusa (Ward.) Urb.
AB  - Turnera diffusa Willd. var. afrodisiaca (Ward) Urb. (syn. T. aphrodisiaca)
      belongs to the family of Turneraceae and is an aromatic plant growing wild in the
      subtropical regions of America and Africa. It is widely used in the traditional
      medicine as e.g. anti-cough, diuretic, and aphrodisiac agent. This work presents
      a 3 min chromatographic analysis using low-pressure (LP) gas chromatography (GC)
      ion-trap (IT) mass spectrometry (MS). The combination of a deactivated 0.6 m x
      0.10 mm i.d., restrictor with a wide-bore CP-Wax 52 capillary column (10 m x 0.53
      mm i.d., 1 microm) reduces the analysis time by a factor of 3-7 in comparison to
      the use of a conventional narrow bore column. Chromatographic conditions have
      been optimized to achieve the fastest separation with the highest signal/noise
      ratio in MS detection. These results allow fast and reliable quality control of
      the essential oil to be achieved.

PMID- 14971494
TI  - Characterization of three agave species by gas chromatography and solid-phase
      microextraction-gas chromatography-mass spectrometry.
AB  - Steam distillation (SD) extraction-solid-phase microextraction coupled to GC-MS
      was developed for the determination of terpenes and Bligh-Dyer extraction
      derivatization coupled with GC for the determination of fatty acids such as ethyl
      esters were used. It was found that the three different Agave species have the
      same profile of fatty acids; the quantity of these compounds is different in each
      Agave variety. On the other hand, different terpenes were identified in the three
      Agave plants studied: nine in A. salmiana, eight in A. angustifolia and 32 in A.
      tequilana Weber var. azul.

PMID- 14971495
TI  - Biotransformation of (R)-(+)- and (S)-(-)-citronellol by Aspergillus sp. and
      Penicillium sp., and the use of solid-phase microextraction for screening.
AB  - The biotransformation of (R)-(+)- and (S)-(-)-citronellol by fungi was studied.
      For screening experiments, solid-phase microextraction (SPME) was used as
      analytical sampling technique. It was found that sporulated surface cultures of
      Aspergillus niger were able to convert the substrate into cis- and trans-rose
      oxides and nerol oxide. The relative contents in the headspace SPME extract of
      the three bioconversion products cis- and trans-rose oxide and nerol oxide were
      up to 54, 21 and 12%, respectively. Rose oxide is found in minor amounts in some
      essential oils, such as Bulgarian rose oil and geranium oil and contributes to
      its unique odor. It is one of the most important fragrance materials in perfumery
      in creating rosy notes. Other bioconversion products were 6-methyl-5-hepten-2
      one, 6-methyl-5-hepten-2-ol, limonene, terpinolene, linalool and alpha-terpineol.
      These bioconversion reactions were confirmed by sporulated surface cultures on
      larger scale and sampling by dynamic headspace sweep and steam distillation
      solvent extraction. The same conversions were noticed with A. tubingensis and
      Penicillium roqueforti. This bioconversion was enantioselective since more of the
      chiral cis- than trans-rose oxide was obtained (cisitrans ratio up to 95/5).
      Submerged liquid cultures of P. roqueforti yielded two unidentified metabolites
      after conversion of citronellol (yield up to 5%). The stability and acid
      catalyzed conversion of citronellol was also investigated. No chemical oxidation
      or auto-oxidation products were detected in acidified liquid control broths up to
      pH 3.5. However, when control tests were run with solid media, acid-catalyzed
      conversion of the substrate to small amounts of cis- and trans-rose oxides, nerol
      oxide, linalool and alpha-terpineol was observed at pH 3.5 and when heat
      treatment (steam distillation solvent extraction) was applied.

PMID- 14971496
TI  - Use of headspace solid-phase microextraction and headspace sorptive extraction
      for the detection of the volatile metabolites produced by toxigenic Fusarium
      species.
AB  - An efficient methodology was developed to determine the growth of toxigenic
      Fusarium spp., based on headspace solid-phase microextraction (SPME) and stir bar
      sorptive extraction of the fungal volatile metabolites produced. SPME and
      headspace sorptive extraction (HSSE) were used to monitor the de novo production
      of sesquiterpene hydrocarbons, such as trichodiene, a volatile marker and
      intermediate in the biosynthesis of trichothecenes. On growth media such as malt
      extract agar and potato dextrose agar, it was found that trichodiene was produced
      by toxigenic strains of Fusarium sambucinum and Fusarium sporotrichioides. It was
      the main volatile metabolite in the headspace extract of the cultures. On the
      other hand, deoxynivalenol producing Fusarium graminearum showed a completely
      different pattern of volatile sesquiterpenes and could easily be distinguished
      from a zearalenone producing strain of F. graminearum based on the headspace
      profile. Hence, it can be concluded that headspace analysis of volatile fungal
      metabolites by SPME and HSSE in combination with gas chromatography/mass
      spectrometry is a suitable monitoring technique to differentiate toxigenic
      strains of Fusarium.

PMID- 14971497
TI  - Molecularly imprinted solid-phase extraction for the screening of
      antihyperglycemic biguanides.
AB  - A new molecularly imprinted polymer (MIP) was specifically synthesized as a smart
      material for the recognition of metformin hydrochloride in solid-phase
      extraction. Particles of this MIP were packed into a stainless-steel tubing (50
      mm x 0.8 mm i.d.) equipped with an exit frit. This micro-column was employed in
      the development of a molecularly imprinted solid-phase extraction (MISPE) method
      for metformin determination. The MISPE instrumentation consisted of a micrometer
      pump, an injector valve equipped with a 20-microl sample loop, a UV detector, and
      an integrator. With CH3CN as the mobile phase flowing at 0.5 ml/min, 95 +/- 2%
      binding could be achieved for 1200 ng of metformin from one injection of a
      phosphate-buffered sample solution (pH 2.5). Methanol + 3% trifluoroacetic acid
      was good for quantitative pulsed elution (PE) of the bound metformin. The MISPE
      PE method, with UV detection at 240 nm, afforded a detection limit of 16 ng (or
      0.8 microg/ml) for metformin. However, the micro-column interacted
      indiscriminately with phenformin with a 49 +/- 2% binding. A systematic
      investigation of binding selectivity was conducted with respect to sample
      composition (including the solvent, matrix, pH, buffer and surfactant effects).
      An intermediate step of differential pulsed elution used acetonitrile with 5%
      picric acid to remove phenformin and other structural analogues. A final pulsed
      elution of metformin for direct UV detection was achieved using 3%
      trifluoroacetic acid in methanol.

PMID- 14971498
TI  - Analysis of Tamm-Horsfall protein by high-performance liquid chromatography with
      native fluorescence.
AB  - Tamm-Horsfall (TH) is a large glycoprotein which originates in the kidney and is
      very abundant in the urine. This protein has been measured mainly by
      immunoassays. Here we describe a different approach for its measurement based on
      high-performance liquid chromatography (HPLC) using a molecular exclusion column
      with native fluorescence detection in the ultraviolet range. This method in
      addition to measuring the level of the protein has the advantage of detecting
      changes in size or aggregation. Urine, 1 ml was mixed with 100 microl of 30% NaCl
      and left at 37 degrees C for 30 min. The urine was centrifuged at 12000 rpm for
      20 s. The precipitate was vortex-mixed and dissolved in a triethanolamine buffer.
      A 20 microl aliquot was injected on a Macrosphere GPC column which was eluted
      with phosphate buffer and the effluent was detected by a fluorometer set at 280
      nm for excitation and 325 nm for emission. Since the protein has a very large
      molecular mass compared to other urinary and serum proteins we did not experience
      any interference. It elutes as the first peak (in approximately 2.5 min on a 500
      A and 2.7 min on 1000 A). The protein precipitates rapidly < 60 min at 37 degrees
      C. The detection in the UV is sensitive for this protein down to 1 mg/l in
      absence of any concentration steps. The method was linear between 1 and 100 mg/l.
      The R.S.D. was 10.4% (mean 62, n = 10). The mean level in 42 normal individuals
      was 31 mg/g creatinine and in 30 patients with proteinuria (different renal
      disorders) was 23 mg/g creatinine.

PMID- 14971499
TI  - Selective extraction of benzoic acid from landfill leachate by solid-phase
      extraction and ion-exchange chromatography.
AB  - In this work a simple method was described for selective extraction of benzoic
      acid from landfill leachate samples. The samples were submitted to solid-phase
      extraction (SPE) with XAD-4 resin as the stationary phase and ion-exchange
      chromatography (IEC) using the ion-exchange resin Amberlyst A-27. The
      instrumental analysis was performed by gas chromatography with mass spectrometric
      detection (GC-MSD). Benzoic acid was isolated, identified and quantified. The
      extraction process is rapid, simple and of low cost. It was also environmental
      friendly, that is, it was used a minimum amounts of hazardous organic solvents
      and produced also minimum quantities of residues.

PMID- 14971500
TI  - Ion-exchange resins in the isolation of nitrogen compounds from petroleum
      residues.
AB  - In this work, preparative liquid chromatography was used for the separation of
      the nitrogen compounds in a sample of heavy gas oil from a Brazilian petroleum.
      Initially it took place a pre-fractionation by neutral aluminium oxide and the
      compounds were separated in different classes such as: hydrocarbons, resins
      (compounds of low molecular mass and intermediate polarity) and asphalthenes
      (polar compounds with high molecular mass). A comparison of the fraction of
      resins was performed by re-fractionating with modified silica (with potassium
      hydroxide and hydrochloric acid), or with ion exchange resins (Amberlyst A-27 and
      A-15), being isolated the basic and neutral compounds, that were analyzed by GC
      MS in the scan and selected ion monitoring modes. Quinolines, benzoquinolines,
      tetrahydroquinolines were found in the basic fraction and carbazoles derivatives
      were found in the neutral fraction.

PMID- 14971501
TI  - Effect of sample composition on electrophoretic migration application to
      hemoglobin analysis by capillary electrophoresis and agarose electrophoresis.
AB  - The electrophoretic migration, in routine analysis, is crucial for compound
      identification especially when multiple components are present in the sample. In
      complex or crude samples, such as those obtained from biological fluids,
      electrophoretic migration often does not correspond well to that of a pure
      standard compound. Several factors, related to the sample itself, have been
      identified as modulating the electrophoretic migration in zone electrophoresis
      both in gel and capillary electrophoresis (CE): solute mobility and
      concentrations, salt content, and protein interaction in the sample. Peak shape
      asymmetry often signals changes in migration especially when comparing samples
      with wide differences in concentration or those containing high ionic strength.
      Also, the migration of a protein can be influenced by the presence of a high
      concentration of another slowly migrating protein in the sample. A weak
      interaction during the separation between the two proteins which lead to a
      decreased velocity has been postulated. This was confirmed by finding a curve
      linear relationship between the ratio of the two hemoglobin (Hb) variants,
      hemoglobin F (Hb F) and hemoglobin S (Hb S), and the distance between the two in
      gel electrophoresis (GE); and also by the observation of formation of a new small
      peak based on the analysis of hemoglobin F by capillary electrophoresis upon the
      addition of Hb S to the separation buffer. These factors when present together
      have an additive effect on the migration. As an example, Hb F, present in low but
      variable concentration in patients with sickle cell disease (Hb S), migrates in
      gel electrophoresis slightly slower than it is expected; enough to be confused
      with other unknown variants. However, the small peaks with different migration
      distances between Hb S and the adult Hb (Hb A) correlated well (r = 0.98) with Hb
      F performed by an alkali-denaturing assay indicating that these peaks are indeed
      Hb F in spite of the difference in their migration.

PMID- 14971502
TI  - Electroosmotic flow reversal for the determination of inorganic anions by
      capillary electrophoresis with methanol-water buffers.
AB  - Manipulation of the electroosmotic flow (EOF) is essential for achieving
      optimized separations of small anions by capillary electrophoresis (CE). In this
      work, efficient suppression or reversal of EOF is achieved upon addition of small
      amounts of the cationic surfactants, cetyltrimethylammonium bromide (CTAB) or
      didodecyldimethylammonium bromide (DDAB) to the electrophoretic buffer. Highly
      stable and reversed EOF are achieved using the surfactants in the presence of up
      to 50% MeOH. In aqueous and low methanol containing solutions (up to 30%, v/v)
      surface aggregation of the surfactants at the capillary wall occurs at a
      concentration below the critical micelle concentration (CMC). The impact of MeOH
      on reversed EOF is predominantly a function of the diminished zeta potential of
      the silica, and to a lesser extent on the CMC in the bulk solution of the
      surfactant. Fast baseline separation and selectivity changes for small inorganic
      anions are observed when mixed aqueous-organic buffers are employed. Changes in
      EOF, micellar properties of the surfactant and selectivity for inorganic anions
      upon addition of various percent of methanol are also discussed.

PMID- 14971503
TI  - On-column synthesis coupled to affinity capillary electrophoresis for the
      determination of binding constants of peptides to glycopeptide antibiotics.
AB  - Binding constants of the glycopeptide antibiotics teicoplanin (Teic), ristocetin
      (Rist), and vancomycin (Van), and their derivatives to D-Ala-D-Ala terminus
      peptides were determined by on-column ligand and receptor synthesis coupled to
      affinity capillary electrophoresis (ACE) or partial filling ACE (PFACE). In the
      first technique, 9-fluorenylmethoxycarbonyl (Fmoc)-amino acid-D-Ala-D-Ala species
      are first synthesized using on-column techniques. The initial sample plug
      contains a D-Ala-D-Ala terminus peptide and two non-interacting standards. Plugs
      two and three contain solutions of Fmoc-amino acid-N-hydroxysuccinimide (NHS)
      ester and buffer, respectively. Upon electrophoresis, the initial D-Ala-D-Ala
      peptide reacts with the Fmoc-amino acid NHS ester yielding the Fmoc-amino acid D
      Ala-D-Ala peptide. Continued electrophoresis results in the overlap of the
      glycopeptide in the running buffer and the plug of Fmoc-amino acid-D-Ala-D-Ala
      peptide and non-interacting markers. Subsequent analysis of the change in the
      electrophoretic mobility (mu) or relative migration time ratio (RMTR) of the
      peptide relative to the non-interacting standards, as a function of the
      concentration of the antibiotic, yields a value for the binding constant. In the
      second technique, derivatives of the glycopeptides Teic and Rist are first
      synthesized on-column before analysis by ACE or PFACE. After the column has been
      partially filled with increasing concentrations of D-Ala-D-Ala terminus peptides,
      a plug of buffer followed by two separate plugs of reagents are injected. The
      order of the reagent plugs containing the antibiotic and two non-interacting
      standards and the anhydride varies with the charge of the glycopeptide. Upon
      electrophoresis, the antibiotic reacts with the anhydride yielding a derivative
      of Teic or Rist. Continued electrophoresis results in the overlap of the
      derivatized antibiotic and the plug of D-Ala-D-Ala peptide. Analysis of the
      change in RMTR of the new glycopeptide relative to the non-interacting standards,
      as a function of the concentration of the D-Ala-D-Ala ligand yields a value for
      the binding constant.

PMID- 14971504
TI  - Micellar electrokinetic capillary chromatography and data alignment analysis: a
      new tool in urine profiling.
AB  - The complex nature of biofluids demands efficient, sensitive and high-resolution
      analytical methodologies to examine how the 'metabolic fingerprint' changes
      during disease. This paper describes how sulphated beta-cyclodextrin-modified
      micellar electrokinetic capillary chromatography (SbetaCD-MECC) has been combined
      with data alignment analysis and may prove a useful new tool in urine profiling,
      allowing for separation of over 80 urinary analytes in under 25 min. The
      optimised and validated SbetaCD-MECC methodology combined with data alignment
      analysis provides rapid identification of 'mismatches' between urine profiles
      which are not easily detected with the naked eye as well as a 'similarity score'
      which indicates the total sum of differences between one profile and another. The
      combination of SbetaCD-MECC with data alignment software should prove a useful
      alternative tool in metabonomic studies for rapid comparison of urine profiles.

PMID- 14971505
TI  - Chiral separation of labetalol stereoisomers in human plasma by capillary
      electrophoresis.
AB  - A newly derivatized cyclodextrin [octakis-(2,3-diacetyl-6-sulfato)-gamma
      cyclodextrin] was investigated as a chiral selector in capillary zone
      electrophoresis in a study of the chiral separation of labetalol stereoisomers.
      Heptakis(2,3-diacetyl-6-sulfato)-beta-cyclodextrin (HDAS-beta-CD) and octakis(2,3
      diacetyl-6-sulfato)-gamma-cyclodextrin (ODAS-gamma-CD) were shown to be effective
      in separating labetalol stereoisomers. Optimal separating conditions of the four
      stereoisomers of labetalol were achieved with 10 mM HDAS-beta-CD and 10 mM ODAS
      gamma-CD in an acidic pH buffer of low molarity. Data illustrating the effects of
      capillary length and cyclodextrin concentration on the separation are presented.
      The longer capillary length and high voltage enabled the baseline separation of
      all isomers in less than 15 min. The optimized method was applied to the analysis
      of human control plasma containing labetalol utilizing solid-phase extraction
      (SPE) in the 96-well format.

PMID- 14971506
TI  - Native fluorescence detection of flavin derivatives by microchip capillary
      electrophoresis with laser-induced fluorescence intensified charge-coupled device
      detection.
AB  - To widen the scope of laser-induced fluorescence (LIF) for detection in microchip
      capillary electrophoresis (CE), a microchip CE LIF-ICCD (intensified charge
      coupled device) system based on a tunable wavelength dye laser pumped by a pico
      second pulse nitrogen laser for excitation and a spectrograph with ICCD for
      detection had developed to demonstrate the enhancement in detection sensitivity
      by the following three approaches: direct detection of native fluorescence,
      improvement of signal-to-noise ratio by pulse laser excitation and time delay
      detection, and selective spectral acquisition by multi-channel detection.
      Riboflavin, flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD)
      have been selected as they are dietetically important and microchip CE provides a
      promising onsite detection method. The results indicate a strong effect of
      wavelength on detection sensitivity and the need to tune wavelength for direct
      detection. Under optimized conditions (excitation 450 nm, emission 520 nm, gate
      delay time 45 ns, 20 mM phosphate buffer at pH 7.1), the following results were
      obtained under static condition: Working ranges (0.6-350 microg/l, r > 0.99),
      detection limits (0.15-1.0 microg/l) and peak height repeatability (1.8-2.2%
      R.S.D.), all within the applicability range for body fluids or beverages such as
      human urine and cow milk. Baseline separation of three flavins was obtained under
      dynamic condition and the fluorescence spectra acquired assist the identification
      of alkaline-degraded products of riboflavin. Thus, the capability to check peak
      purity and identify unknown peaks has been demonstrated.

PMID- 14971507
TI  - Fabrication of calcium fluoride capillary electrophoresis microdevices for on
      chip infrared detection.
AB  - In this paper, we demonstrate microfluidic capillary electrophoresis (CE) devices
      made in CaF2 , for optical detection in a broad spectral range. We have designed
      methods for micromachining and enclosing capillaries in CaF2. The utility of
      these microdevices has been shown through CE analysis of fluorescently labeled
      amino acids. We have also performed infrared spectroscopy for analyte
      identification in microfluidic CaF2 channels. These CaF2 microdevices open the
      door to microchip separations with optical detection in the ultraviolet, visible,
      and infrared spectral regions.

PMID- 14971508
TI  - Parametric investigation on the effect of channel topologies on electrophoretic
      separations.
AB  - This paper presents a systematic study that illustrates the importance of the
      topologies of microchannels on electrokinetically based separation. Using
      theoretical and numerical analyses, we designed and showed that topologies that
      significantly increased the surface-to-volume ratio of the channel can provide
      dramatic improvement in the ability of the channel both to dissipate the heat
      generated by Joule heating and to reduce the axial dispersion associated with the
      siphoning effect. The incremental benefit and tradeoff of geometric complexity
      was also evaluated. The improvement offered by topographically patterned
      channels, such as finned structures, is especially pertinent in the development
      of preparative or semi-preparative scale electrokinetically driven separations,
      such as capillary electrophoresis and capillary electrochromatography, in which
      large cross sections of channels are required to achieve the needed volumetric
      throughput.

PMID- 14971509
TI  - Low-dispersion electrokinetic flows for expanded separation channels in
      microfluidic systems: multiple faceted interfaces.
AB  - A novel methodology to design on-chip conduction channels is presented for
      expansion of low-dispersion separation channels. Designs are examined using two
      dimensional numerical solutions of the Laplace equation with a Monte Carlo
      technique to model diffusion. The design technique relies on trigonometric
      relations that apply for ideal electrokinetic flows. Flows are rotated and
      stretched along the abrupt interface between adjacent regions having differing
      specific permeability. Multiple interfaces can be placed in series along a
      channel. The resulting channels can be expanded to extreme widths while
      minimizing dispersion of injected analyte bands. These channels can provide a
      long path length for line-of-sight optical absorption measurements. Expanded
      sections can be reduced to enable point detection at the exit section of the
      channel. Designed to be shallow, these channels have extreme aspect ratios in the
      wide section, greatly increasing the surface-to-volume ratio to increase heat
      removal and decrease unwanted pressure-driven flow. The use of multiple
      interfaces is demonstrated by considering several three-interface designs.
      Faceted flow splitters can be constructed to divide channels into any number of
      exit channels while minimizing dispersion. The resulting manifolds can be used to
      construct medians for structural support in wide, shallow channels.

PMID- 14971510
TI  - Molecularly imprinted polymeric film on semiconductor nanoparticles analyte
      detection by quantum dot photoluminescence.
AB  - Incorporation of semiconductor nanoparticles into molecularly imprinted polymer
      provides a sensor material which can be easily shaped and with better selectivity
      because the bound template would quench the photoluminescence (PL) emission of
      quantum dots significantly. In this work, artificial receptors of various
      templates were synthesized with functional monomers such as methacrylic acid
      (MAA), semiconductor like CdSe/ZnS core-shell derivatized with 4-vinylpyridine
      and ethylene glycol dimethacrylic acid as the cross-linker. The quenching of
      photoluminescence emissions is presumably due to the fluorescence resonance
      energy transfer between quantum dots and template molecules. The
      photoluminescence emission is unaffected upon incubation of analyte with the
      blank control polymer.

PMID- 14971511
TI  - Photo-lithographically impregnated and molecularly imprinted polymer thin film
      for biosensor applications.
AB  - A voltammetric sensor for albuterol was investigated where we combined the
      techniques of microfabrication and molecular imprinting to construct on-chip
      devices using photoirradiation of cross-linkable polymers. Molecularly imprinted
      polymer was coated as a thin film onto the gold working electrode on chip and the
      analyte was directly quantified by differential pulse voltammetric measurements.

PMID- 14971512
TI  - Trilinear chemometric analysis of two-dimensional comprehensive gas
      chromatography-time-of-flight mass spectrometry data.
AB  - Two-dimensional comprehensive gas chromatography (GC x GC) is a powerful
      instrumental tool in its own right that can be used to analyze complex mixtures,
      generating selective data that is applicable to multivariate quantitative
      analysis and pattern recognition. It has been recently demonstrated that by
      coupling GC x GC to time-of-flight mass spectrometry (TOFMS), a highly selective
      technique is produced. One separation on a GC x GC/TOFMS provides retention times
      on two chromatographic columns and a complete mass spectrum for each component
      within the mixture. In this manuscript, we demonstrate how the selectivity of GC
      x GC/TOFMS combined with trilinear chemometric techniques such as trilinear
      decomposition (TLD) and parallel factor analysis (PARAFAC) results in a powerful
      analytical methodology. Using TLD and PARAFAC, partially resolved components in
      complex mixtures can be deconvoluted and identified using only one data set
      without requiring either signal shape assumptions or fully selective mass
      signals. Specifically, a region of overlapped peaks in a complex environmental
      sample was mathematically resolved with TLD and PARAFAC to demonstrate the
      utility of these techniques as applied to GC x GC/TOFMS data of a complex
      mixture. For this data, it was determined that PARAFAC initiated by TLD performed
      a better deconvolution than TLD alone. After deconvolution, mass spectral
      profiles were then matched to library spectra for identification. A standard
      addition analysis was performed on one of the deconvoluted analytes to
      demonstrate the utility of TLD-initiated PARAFAC for quantification without the
      need for accurate retention time alignment between sample and standard data sets.

PMID- 14971513
TI  - Simulation of chromatography of phenolic compounds with a computational chemical
      method.
AB  - An ab initio simulation of reversed-phase liquid chromatography for phenolic
      compounds was achieved based on molecular interaction energy values calculated
      using molecular mechanics calculations (MM2) of the CAChe program. The precision
      of the predicted retention factors from the molecular interaction energy values
      was equivalent to the predicted retention factors based on octanol-water
      partition coefficients (log P) calculated using the molecular orbital package
      (MOPAC). The prediction of retention factors of phenolic compounds in reversed
      phase liquid chromatography in a given pH eluent was possible using the predicted
      dissociation constant (pKa) from the atomic partial charge without a chemical
      experiment if the organic modifier effect was known.

PMID- 14971514
TI  - Determination of magnetic susceptibility of various ion-labeled red blood cells
      by means of analytical magnetapheresis.
AB  - Analytical magnetapheresis is a newly developed technique for separating
      magnetically susceptible particles. The magnetically susceptible particles are
      deposited on a bottom plate after flowing through a thin (< 0.05 cm) separation
      channel under a magnetic field applied perpendicular to the flow. Particles with
      various magnetic susceptibilities can be selectively deposited and separated by
      adjusting the applying magnetic force and flow rates. Magnetic susceptibility is
      an important parameter for magnetic separation. Magnetic susceptibility
      determination of various ion-labeled red blood cells (RBCs) using analytical
      magnetapheresis with a simple theoretical treatment is reported in this study.
      Susceptibility determination is based on the balance between maximal channel flow
      rate and magnetically induced flow rate for deposition. We tried a new approach
      to determine particle magnetic susceptibilities using a balance of magnetic and
      drag forces to control magnetically induced particle velocities. The Er3+, Fe3+,
      Cu2+, Mn2+, Co2+, and Ni2+ ions were used to label RBC at various labeling
      concentrations for susceptibility determination. The susceptibilities determined
      for various ion-labeled RBC under two magnetic field intensities fell within a
      10% range. The average viabilities of various ion-labeled RBCs were 96.1 +/-
      0.8%. The susceptibility determination generally took less than 10 min.
      Determined susceptibilities from analytical magnetapheresis differed by 10% from
      reference measurements using a superconducting quantum interference device
      (SQUID) magnetometer. The cost and time for analysis is much less using
      analytical magnetapheresis. This technique can provide a simple, fast, and
      economical way for particle susceptibility determinations.

PMID- 14971515
TI  - Long-term follow-up of erythema nodosum.
AB  - One hundred and fifty-four patients with erythema nodosum who attended the skin
      clinic at Ramathibodi Hospital from January 1990 to December 2000 were evaluated
      retrospectively with regard to the etiology of erythema nodosum. Of 49 patients
      who attended the skin clinic during that time 26 returned for reevaluation. Of
      the 154 patients, their ages ranged from 10-72 years old; 138 were females, 16
      were males. The most common cause of erythema nodosum was tuberculosis (12.3%).
      Upper respiratory tract infection was found in 3.9 per cent. Other causes
      included Behcet's disease, sytemic lupus erythematous, drugs, pregnancy, chronic
      myeloid leukemia, leprosy, Reiter's syndrome and inflammatory bowel disease. Of
      the 26 patients who returned for reevaluation, pulmonary tuberculosis was
      identified in only one patient who had developed erythema nodosum 16 months
      earlier. In conclusion, it was found that tuberculosis is still a predominant
      cause of erythema nodosum among Thai patients.

PMID- 14971516
TI  - The remained patellar tendon strength after central one third removal : a
      biomechanical study.
AB  - The study was aimed at comparing the ultimate load bearing capabilities between
      normal patellar tendons (control group) and tendons after central one-third
      removal (removal group). Eleven fresh Thai cadavers provided study specimens. The
      average age of the cadavers was 24.86 +/- 7.13 years. Five tendons were used as
      control specimens and another six tendons underwent central one-third removal.
      The Instron 5583 testing machine and Cooper's technique of measurements were used
      to test the ultimate load. Rate of elongation of tendon was set at 500 mm/sec.
      The results showed that the removal group cross-sectional area was 48.67 mm2 or
      49.64 per cent of the control group (98.04 mm2). The mean ultimate load of the
      control group was 4,365.59 N. The mean ultimate load of the removal group was
      2,226.58 N or about 51 per cent. The energy level to breaking point in the
      control group was 72.17 J and 32.58 (45.14%) in the removal group. The average
      width of the central one-third portion was measured at 8.68 +/- 0.56 cm.
      Generally in a clinical situation, when the ultimate load is reduced to about
      half in the donor knee, care must be taken before allowing full weight to bear.
      Caution should also be emphasized in cases where a routinely 10 mm wide graft has
      been taken, as the donor tendon may be weakened by more than half and may rupture
      prematurely.

PMID- 14971517
TI  - The Aging Males' Symptoms rating scale: cultural and linguistic validation into
      Thai.
AB  - The interest in clinically investigating the health-related quality of life and
      symptoms of aging males has increased in recent years. Recently, a couple of
      validated questionnaires have been proposed for either screening, diagnosing and
      assessing response to therapy. Among these, the Aging Males' Symptom (AMS)
      questionnaire has been one of the most accepted questionnaires used in aging male
      clinics worldwide. The AMS questionnaire was originally developed and
      standardized in Germany in accordance with psychometric tests, and translated
      into English. The objective of this study was to develop the Thai AMS
      questionnaire, which is culturally and linguistically validated, and to present
      the translation process from English to Thai. The translation for the Thai
      speaking culture was planned specifically for use in Thailand. The forward
      translation into Thai was performed independently by two Thai-English translators
      with clinical experience in the aging male field. Another two Thai-English
      translators performed the back translation into English. Reconciliation of
      problematic items or explanations with the investigators was performed point by
      point to get the final version. The test and retest of Thai AMS questionnaire
      were performed within the time interval of 14 days by 20 Thai men aged 41-62 who
      came from different social classes and had various levels of education. The
      correlation between the first and the second questionnaires was statistically
      analyzed using Pearson correlation coefficient (r). The results of the linguistic
      and cultural adaptation of the English AMS scale led to a Thai AMS questionnaire.
      The results of the test and retest reliability demonstrated good correlation and
      were promising (r = 0.87). Therefore, this scale can be used as a valuable tool
      for assessing symptoms in the aging males in Thailand.

PMID- 14971518
TI  - Epidemiology of spinal cord injuries: a study in the Spinal Unit, Siriraj
      Hospital, Thailand, 1997-2000.
AB  - A prospective study of 83 patients with spinal cord injuries admitted to the
      Spinal Unit, Siriraj Hospital, Bangkok, Thailand from January 1997 to December
      2000 was conducted. The average age was 33.2 +/- 11.7 years (range from 10 to 68
      years) with a male: female ratio of 4 : 1. Most subjects (83.2%) were aged
      between 16-45 years. About half of them had no associated injuries and no
      financial problems. Three-fourths of the spinal injuries were caused by traffic
      accidents (49.4 and 25.3% car and motorcycle respectively). The other two causes
      were falls (16.9%) and gunshot wounds (8.4%). The neurological classification was
      as follows: 34 (41.0%) patients had ASIA D grade of injury, 28 (33.7%) were
      paraplegic with ASIA A, B or C grade and 21 (25.3%) were tetraplegic with ASIA A,
      B, or C grade. Traffic accidents most frequently resulted in an incomplete ASIA D
      grade (40.3%). Males were more predominant for all causes of injury especially
      motorcycle accidents. The average Barthel Index score was 24.3 +/- 24.7 and 51.9
      +/- 31.8 at admission and discharge respectively. The prevalence of depression
      was 24.1 per cent. The average length of stay for the depressed and non-depressed
      groups was 117.4 +/- 59.1 and 73.4 +/- 54.4 days respectively.

PMID- 14971519
TI  - Immune response of intradermal hepatitis B vaccination at lower dose versus
      intramuscular vaccination at double standard dose in predialytic chronic renal
      failure patients.
AB  - The immune responses to hepatitis B vaccine were studied in 2 groups of
      predialytic chronic renal failure patients who had negative results of hepatitis
      B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs) and hepatitis
      B core antibody (anti HBc). In the intradermal group, vaccine at the dose of 0.1
      ml, 2 microg, was intradermally administered at 5 positions. In the intramuscular
      group, the vaccine at the dose of 1.0 ml, 20 microg, was intramuscularly given at
      2 positions and, thus, was a double standard dose. Both groups received 4
      vaccinations at month 0, 1, 2, and 6 (M0, M1, M2, and M6). The results showed
      that there were no significant differences in the results of seroconversion
      rates, defined as having anti HBs levels above 10 mIU/ml, between the intradermal
      (ID) and intramuscular (IM) groups at M1, M2, M6, and M7. In patients with
      positive seroconversion results at M7, the numbers of patients in the good and
      excellent subgroups, having HBs Ab levels ranged 10-999 and above 1,000 mIU/ml
      respectively, showed no difference between both routes. The body weight and
      seroconversion rates at M2 and M6 were the factors which had a positive influence
      on the seroconversion rates of intradermal hepatitis B vaccination. In
      conclusion, intradermal hepatitis B vaccination at a lower dose could provide
      comparable satisfactory immune response with the intramuscular route at double
      the standard dose.

PMID- 14971520
TI  - Deadspace: a potential error in concentration of medication during dilutional
      process in neonates.
AB  - OBJECTIVE: To evaluate the volume of deadspace (DS) and degree of errors in
      concentration of medications during medication dilution with needle removable
      syringe (NRS) compared to needle nonremovable syringe (NNRS). MATERIAL AND
      METHOD: 300 syringes were tested and divided into 3 groups as follows: The first
      group was 100 syringes of needle removable insulin 1 ml syringe (NRIS) with a 27
      gauge needle (Terumo), the second group was 100 syringes of NRIS with a 27 gauge
      needle (Nipro) and third group 3 was 100 syringes of needle non removable insulin
      syringe (NNRIS) with a 27 gauge needle (Terumo). All syringes with needle sets
      (without needle cover) were weighed with a Mettler electronic balance. Volume of
      DS was measured and calculated using a standard method. 10 syringes of each group
      were randomly selected to test for degree of errors in concentration of
      medications during the dilutional process using standard insulin (310 micro unit
      per ml) as a medication for dilution. All specimens were collected by ejecting
      all diluents into collecting tubes and insulin concentrations were measured using
      radioimmunoassay technique (insulin-CT biointernational, France) twice in each
      sample. Concentration was then calculated back and the results were noted and
      analysed. RESULTS: Means of DS in group 3 (2.4 +/- 0.8 microl) was significantly
      less than group 1 (49.7 +/- 00.9 microl) and group 2 (65.3 +/- 0.7 microl)
      (median = 2 microlitre). All three groups were significantly different from each
      other with the largest DS in group 2. After dilution, insulin concentrations from
      diluents in group 3 were still close to standard insulin (335 +/- 28 vs 310
      microunits/ml), whereas group 1 and 2 were significantly higher than group 3 (1.7
      and 1.9 times) and standard insulin (1.8 and 2 times). CONCLUSIONS: DS in NRIS is
      not negligible and is considered a potential source of error in the concentration
      of medications when it is used to dilute parenteral medications in the neonatal
      intensive care unit (NICU).

PMID- 14971521
TI  - The cost-effectiveness of mini peak expiratory flow as a screening test for
      chronic obstructive pulmonary disease among the Bangkok elderly.
AB  - This study aims to explore the cost-effectiveness of Mini Peak Expiratory Flow
      (miniPEF) as a screening test for Chronic Obstructive Pulmonary Disease (COPD)
      among the elderly in 124 urban communities around Siriraj Hospital, using the
      gold standard of diagnosis based on the guidelines of the Thoracic Society of
      Thailand. There were 3,094 subjects who participated and completed all the tests.
      The results showed that the cut-off miniPEF percentage of predicted value of
      highest average accuracy was 62 per cent. The sensitivity was 72.7 per cent (95%
      CI 67.0-78.6) and the specificity was 81.1 per cent (95% CI 79.7-82.5) The cost
      of screening 19 elderly to detect one case of COPD is 923 baht, with a false
      negative rate of 1.9 per cent (95% CI 1.3-2.5%) and a false positive rate of 17.5
      per cent (95% CI 15.4-19.6%). It is suggested that measuring a miniPEF is
      regarded as one of the cost-effective screening tests for COPD in the elderly.

PMID- 14971522
TI  - The most cost-effective screening method for chronic obstructive pulmonary
      disease among the Bangkok elderly.
AB  - Our previous studies demonstrated the high prevalence and incidence of Chronic
      Obstructive Pulmonary Disease (COPD) among the Bangkok elderly, as well as the
      cost-effectiveness of a questionnaire, chest radiography, and mini peak
      expiratory flow rate (miniPEF) as screening tools. This final study aimed to
      identify the most cost-effective screening method among individual, serial and
      parallel combinations of the above tools, based on the guidelines for diagnosing
      COPD of the Thoracic Society of Thailand. There were 3,094 elderly aged 60 years
      and over in 124 urban communities around Siriraj Hospital who participated and
      completed all the tests. The results showed that the most cost-effective
      screening method was the miniPEF at cut-off percentage of 62 per cent of
      predicted value. This needed to screen 19 elderly people at a cost of 923 baht to
      detect one case of COPD, with a false negative rate of 1.9 per cent (95%CI 1.3
      2.5), a false positive rate of 17.5 per cent (95%CI 15.4-19.6). The questionnaire
      is the alternative choice of screening tool.

PMID- 14971523
TI  - Prevalence of idiopathic long QT syndrome in congenital sensori-neural hearing
      loss students of Songkhla School for the Deaf.
AB  - OBJECTIVES: To survey the prevalence of the long QT syndrome (LQTS), especially
      Jervell-Lange-Nielsen syndrome (JLNS), in Thai children (The first such study).
      BACKGROUND: LQTS is a rare inherited disease with a prevalence of 0.21 per cent
      in children with congenital deafness from other reports. These patients carry a
      high risk of recurrent syncope and fatal ventricular arrhythmia. STUDY DESIGN:
      Cross-sectional survey from January 2000 to August 2000. METHOD: A total of 276
      children with congenital sensori-neural hearing loss were included. A
      questionnaire was employed and all children were examined by a pediatric
      cardiologist to rule out organic heart disease. EKGs were obtained and QTc
      intervals were blindly measured using standard methods in L2, V5 or any other
      leads with the longest QTc interval by three pediatric cardiologists. If QTc
      interval is prolonged, additional EKG (up to 3) were done to confirm the finding.
      Schwartz criteria was used to identify index cases with LQTS after repeated EKGs,
      and exercise stress tests. Also, echocardiography were done in patients suspected
      of having LQTS. RESULTS: A total of 14 children needed a third EKG and more work
      ups due to persistent long QTc interval after 2 consecutive EKG studies with QTc
      intervals ranged from 456 msec to 466 msec, and Schwartz score from 1.5 to 2.5.
      There were 6 twins and no triplets in the study. Finally, two subjects (not twins
      or siblings) had persistent prolonged QTc intervals after 3 EKG studies. After
      the exercise stress test, both still had a prolonged QTc interval, not corrected
      to the normal QTc interval even at the exercise peak. There was no cardiac
      abnormality either structurally or functionally from the 2D echocardiogram and
      Doppler color flow study. CONCLUSION: The possible prevalence of JLNS was 0.7 per
      cent (2/276). Both children were in the low-risk group for having LQTS.

PMID- 14971524
TI  - Methyldopa supplement for resistant essential hypertension: a prospective
      randomized placebo control crossover study.
AB  - BACKGROUND: Resistant hypertension is an important public health problem, its
      prevalence varies between 30 to 50 per cent. However, there is no definite
      recommendation for the treatment of resistant hypertension (HT). MATERIAL AND
      METHOD: A prospective randomized placebo control crossover study in resistant HT
      was designed to compare safety and efficacy between methyldopa 250 mg twice daily
      and placebo using ambulatory blood pressure monitoring. RESULTS: 87 from 1,112
      cases (7.82%) from the hypertension clinic of Vajira Hospital were found to have
      clinical resistant HT and 40 cases were accepted to enrolled in the study. 23
      cases of true resistant HT proceeded to the treatment phase of the study and all
      of them completed the study. Methyldopa reduced systolic blood pressure (BP) from
      153.67 to 135.23 mmHg, or -18.44 mmHg (95% confidence interval 15.13-21.75).
      Diastolic BP was reduced from 86.42 to 74.90 mmHg, or -11.52 mmHg (95% confidence
      interval 9.41-13.63). CONCLUSION: The addition of methyldopa to the optimal
      medical therapy contributed to the improvement of BP control among patients with
      resistant HT.

PMID- 14971525
TI  - Oral bacterial flora of dogs with and without rabies: a preliminary study in
      Thailand.
AB  - The authors studied the bacterial flora of the dog oral cavity and of bite
      wounds, Aerobic bacteria were isolated from mouth swabs of 16 normal and 5 rabid
      dogs as well as from infected dog-bite wounds from 18 patients. A total of 20
      different microbial species were recovered from mouth swab cultures. The most
      frequently isolated organisms were Klebsiella pneumoniae ssp pneumoniae,
      Escherichia coli, Staphylococcus aureus, Citrobacter freundii, Enterobacter
      cloacae, Acinetobacter calcoaceticus, and Pasteurella species. There were no
      differences in the aerobic bacterial flora between rabid and nonrabid dogs. From
      the cultures of the bite wound swabs, the authors found that almost all of the
      organisms identified were part of the normal oral flora of the dog. One or more
      aerobic bacteria were isolated from the infected dog-bite wounds. Two patients
      had four, 3 had three, 4 had two, and 6 had one of the nine organisms in their
      wounds. The predominant species of bacteria involved in infection of bite wounds
      were, as follows: Staphylococcus aureus, Pasteurella multocida, E. coli,
      Moraxella species, Pasteurella canis, and Enterobacter cloacae. However, three
      wound cultures had no aerobic bacterial growth. The results of this study show
      that the infected bite wounds may contain a mixed bacterial flora that colonize
      human skin and the oral cavity of dogs.

PMID- 14971526
TI  - A questionnaire for measuring patient satisfaction to general anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Measurement of patient satisfaction to general
      anesthesia needs a valid and reliable tool to cover all dimensions of
      satisfaction. However, there is no standard tool in a Thai version for
      measurement of this satisfaction. The objective of this study was to develop a
      valid and reliable tool for measurement of patient satisfaction to general
      anesthesia. METHOD: Review of the medical literature and patients' interviews
      were performed to generate the ideas and dimensions of satisfaction. Items were
      generated according to customer satisfaction. The pilot questionnaire was set and
      verified for content validity by item correlation. One item of low item
      correlation was deleted. The pilot study was performed by application of the
      pilot questionnaire to patients to detect problems on processes to derive
      responses and problems of the questionnaire. Another two items were excluded due
      to high missing responses. The results of reliability analysis were satisfactory.
      Revision of the pilot questionnaire was taken eventually into the final
      questionnaire. Then, the final questionnaire was processed to obtain Cronbach's
      alpha coefficient at King Chulalongkorn Memorial Hospital. Finally, retest for
      reliability was taken at Police General Hospital in order to prove its
      generalization. RESULTS: The constructed final questionnaire composed of ten
      items. All item correlations were higher than 0.5. Cronbach's alpha coefficients
      obtained in King Chulalongkorn Memorial Hospital and Police General Hospital were
      0.8775 and 0.7571, respectively. CONCLUSION: The developed questionnaire was
      qualified for both validity and reliability. Also verified for the wide
      application in another hospital.

PMID- 14971527
TI  - Medical ethics and practice.

PMID- 14971528
TI  - Alleviation of the climacteric symptoms with oral sequential hormone replacement
      therapy.
AB  - The efficacy of the oral hormone replacement therapy (HRT) preparation estradiol
      valerate/levonorgestrel (EV/LNG, Klimonorm) in the alleviation of the menopausal
      complaints of peri- and postmenopausal Thai women was studied in a prospective,
      open, uncontrolled phase IV clinical trial. Of the 50 peri- or postmenopausal
      women screened, 39 completed the study. From them 31 were postmenopausal and 8
      perimenopausal. The participants received EV/LNG over a period of 6 cycles. The
      Menopause Rating Scale II (MRS II) was used to assess the effect of EV/LNG on the
      menopausal symptoms. The changes in the main parameters of the MRS II during the
      treatment with EV/LNG showed that the general score decreased by 34.9 per cent
      after 3 months and was kept at the same value after 6 months of treatment. The
      somato-vegetative complaints decreased by 32.5 per cent after 3 months and by 35
      per cent after 6 months. The psychological complaints decreased by 34.1 per cent
      after 3 months and by 32.9 per cent after 6 months. The urogenital complaints
      decreased by 29.3 per cent after 3 months, and remained at the same level after 6
      months of treatment. In conclusion, the 6-months administration of the oral HRT
      preparation estradiol valerate/levonorgestrel caused a considerable alleviation
      of the climacteric symptoms in menopausal women.

PMID- 14971529
TI  - Prevention and control of thalassemia at Saraburi Regional Hospital.
AB  - OBJECTIVE: To evaluate the program in prevention and control of thalssemia among
      pregnant women and their spouses, prevention of new cases by screening tests,
      confirmatory test, genetic counselling, prenatal diagnosis, and selective
      abortion. SUBJECTS: The pregnant women, attending antenatal care unit, Saraburi
      center hospital, as well as their spouses. 1 January 2000-31 December 2001
      METHOD: As part of the antenatal care assessment, pregnant women before 16 weeks
      gestation were screened, with pre- and post-test counselling, by osmotic
      fragility (OF) and dichorophenol indophenol precipitate (DCIP) tests, and
      confirmed by complete blood count (CBC), mean corpuscular volume (MCV),
      hemoglobin typing and polymerase chain reaction for alphathal1 (PCR alphathal1)
      if any of two screening tests was positive. The husbands of those who were
      carriers of severe thalassemia were encouraged to have thalassemia screening and
      confirmation. When both the pregnant women and their husbands were carriers of
      severe thalassemia, the pregnant women would voluntarily perform the prenatal
      diagnosis. Termination of pregnancy would be offered when the fetus had severe
      thalassemia. RESULTS: There were 3,739 from 4,214 women (88.7% of all antenatal
      women), who participated in the program. OF and/or DCIP were positive in 1,742 of
      3,739 subjects (46.5%). Of those, 960 from 1,742 (55.1%), had husbands who were
      willing to have the testing, and OF and/or DCIP were positive in 443 of 960 cases
      (46.1%). The confirmatory tests revealed carrier and disease of thalassemia, and
      hemoglobinopathies in 931 of 1,742 women (53.9%), and 135 of 960 husbands
      (14.0%). The 20 couples who had the possibility of having severe thalassemic
      newborns, were strongly advised to have prenatal diagnosis. The 12 risk
      pregnancies had been performed cordocentesis. Finally 3 of 12 (25.0%) fetuses
      were documented to have severe thalassemia and all of them decided to have
      selective abortion. CONCLUSIONS: The screening model for thalassemia carriers by
      using the combination of OF and DCIP is the easy screening model. It can be done
      quickly, it is inexpensive, therefore it is suitable for large numbers of
      population screening. The systematic screening, confirmatory of thalassemia
      diagnosis and prenatal diagnosis are the measure of thalassemia prevention and
      control, and aims to decrease the number of newborns with severe thalassemia.

PMID- 14971530
TI  - Effectiveness of vaginal douching on febrile and infectious morbidities after
      total abdominal hysterectomy: a multicenter randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of vaginal douching with 1 per cent
      povidone-iodine in reducing febrile and infectious morbidities after total
      abdominal hysterectomy (TAH). METHOD: The authors conducted a randomized
      controlled trial in 300 patients undergoing elective TAH in three hospitals in
      Northeast Thailand: a university, a regional and a general hospital. The patients
      were randomly allocated to the intervention or control groups. Patients in the
      intervention group received pre-operative vaginal douching with 1 per cent
      povidone-iodine while patients in the control group did not. External evaluators
      not apprised of the intervention assessed febrile and infectious morbidities.
      RESULTS: 300 patients were enrolled in the study. The incidences of febrile
      morbidity in patients with and without pre-operative vaginal douching were 25 and
      35 per cent, respectively, though not statistically significant (risk difference 
      9.6%, 95% CI -19.9%, 0.8%, adjusted odds ratio 0.6, 95% CI 0.3%, 1.0%). A
      statistically significant difference in infectious morbidity was found between
      the groups (8 vs 19%, risk difference -10.0%, 95% CI -17.8%, -2.2%, adjusted odds
      ratio 0.4, 95% CI 0.2%, 0.9%). CONCLUSION: Pre-operative vaginal douching with 1
      per cent povidone-iodine significantly reduces infectious morbidities after TAH.

PMID- 14971531
TI  - Two doses of oral sustained-release tramadol do not reduce pain or morphine
      consumption after modified radical mastectomy: a randomized, double blind,
      placebo-controlled trial.
AB  - BACKGROUND: Tramadol is a weak opioid agonist with antinociceptive effects
      through its action on the mu-receptor and by inhibiting the neuronal re-uptake of
      both noradrenaline and serotonin. Tramadol is commonly used for treatment of mild
      to moderate post-operative pain. An oral form of sustained-release tramadol (SR)
      was recently formulated for reducing the administration frequency from qid to
      bid. OBJECTIVE: To evaluate the analgesic efficacy and safety of two doses of
      oral tramadol SR for the treatment of pain after modified radical mastectomy.
      STUDY DESIGN: Randomized, double blind, placebo-controlled trial. METHOD: Fifty
      women were randomly allocated to receive either tramadol SR 100 mg (group T), or
      placebo tablet (group P) orally approximately 1 hour before surgery with a repeat
      dose administered 12 hours later by nurses not apprised of the patient groupings.
      All patients received the standard general anesthesia. Post-operatively, nurses
      in the research team assessed pain using a visual analog scale 0-100 mm at rest
      (rVAS) and during arm movements (mVAS) at admission to postanesthesia care unit
      (PACU) (T0) and 2 (T2), 6 (T6), 12 (T12) and 24 (T24) hours after surgery. Rescue
      analgesia was provided for 24 hours via a morphine-loaded patient-controlled
      analgesia (PCA) device at 1 mg bolus with a 5-minute lockout interval. Cumulative
      morphine consumption and adverse events were recorded. RESULTS: Twenty-five
      patients with comparable baseline characteristics from each group were studied.
      The proportions of patients with VAS > 30 (both rVAS and mVAS) at each
      measurement period were not significantly different between the groups except for
      the mVAS at T24, where the proportion in group T was higher than group P (48% vs
      20%, 95% CI of difference: -53%, -3%, p = 0.04). The median morphine consumption
      in both groups at T2, T6, T12 and T24 were comparable. No serious adverse effects
      were observed; however, patients in group T reported nausea and vomiting more
      than group P (56% vs 24%, p = 0.02). CONCLUSION: Two doses of oral tramadol SR
      100 mg had no effect on post-operative pain scores and morphine consumption in
      patients who underwent modified radical mastectomy. In fact, more patients in the
      tramadol group reported nausea and vomiting than the placebo group.

PMID- 14971532
TI  - Efficacy and safety of Pueraria mirifica (Kwao Kruea Khao) for the treatment of
      vasomotor symptoms in perimenopausal women: Phase II Study.
AB  - OBJECTIVES: To evaluate the preliminary efficacy and safety of Pueraria mirifica
      in the treatment of vasomotor symptoms. DESIGN: Open-label study. SETTING: Hat
      Yai Regional Hospital, Thailand. SUBJECTS: Pre and postmenopausal women with
      vasomotor symptoms, such as hot flushes and night sweats. Other unpleasant
      symptoms, urogenital and psychological symptoms, were also evaluated. MATERIAL
      AND METHOD: Patients were enrolled voluntarily and randomly received 50 mg or 100
      mg of Pueraria mirifica in capsules, once daily for six months. RESULTS: Of the
      48 enrolled patients, 11 cases were excluded for failing to complete the initial
      work-up. Thirty-seven cases were evaluated. 20 of 37 (54.1%) randomly received a
      dose of 50 mg/day of Pueraria mirifica (Group A), and 17 of 37 (45.9%) received
      100 mg/day of Pueraria mirifica (Group B). The mean of the modified Greene
      climacteric scale decreased from 35.6 to 26.6, 17.2 and 15.1 in group A, while
      group B, declined from 32.6 to 21.0, 14.8 and 13.6 at 1-, 3- and 6-month
      respectively. The mean serum estradiol, fluctuated from the baseline of 76.6 to
      55.4, 56.7, 72.5, 69.2, 114.2 and 74.5 pg/ml at 1-, 2-, 3-, 4-, 5- and 6-month
      respectively. Whereas the mean serum follicle-stimulating hormone
      (FSH)/luteinizing hormone (LH) was stable in the range of; 27.1/12.6, 28.3/12.9
      and 22.5/11.4 mIU/ml at baseline, 3- and 6-month respectively. CONCLUSIONS:
      Pueraria mirifica, containing phytoestrogens, relatively alleviated the
      climacteric symptoms in perimenopausal women. The transient negative profiles
      occurred in a small number of subjects that included anemia, and liver profiles.
      While there was a slight decrease in lipoproteins and an increase in hormonal
      profiles, Pueraria mirifica demonstrates great promise in the treatment of
      climacteric symptoms among perimenopausal women. However, optimal doses should be
      clinically assessed, to meet appropriate individual responses.

PMID- 14971533
TI  - Clinical characteristics of colorectal polyp in Thai children: a retrospective
      study.
AB  - BACKGROUND: It was believed that more than 90 per cent of children with
      colorectal polyp had a single lesion, located in the rectosigmoid colon,
      therefore, sigmoidoscopy with polypectomy was the treatment of choice. After a
      wide use of pediatric colonoscopy, this concept has been changed. MATERIAL AND
      METHOD: This study was aimed to describe clinical characteristics of colorectal
      polyp in Thai children. Medical records of children with colorectal polyp were
      retrospectively reviewed. Comparison between polyposis coli and children with
      less than 5 polyps were also analyzed. RESULTS: There were 93 patients, 43
      females and 50 males. The average age was 5.1 years. Lower GI bleeding and
      prolapse of rectal polyp comprised the two most common presentations, 93.5 and
      39.8 per cent, respectively. The mean duration of symptoms was 5.6 months. Only
      50.6 per cent had rectal polyp noted by digital examination. Investigations
      included sigmoidoscopy (n = 77), colonoscopy (n = 16), and barium enema (n = 16).
      Eight per cent of the cases had more than 5 polyps. Location of the polyps was
      noted in the rectosigmoid colon (88.2%), descending colon (4.3%), right-sided
      colon (4.3%), and pancolonic (3.2%). Of all the patients, 11.8 per cent had the
      polyp above the rectosigmoid region, whereas 50 per cent of those who underwent
      colonoscopy (n = 16) had the polyps noted proximal to this region. Older age,
      lower hematocrit, and more frequent right-sided polyps were significantly
      associated with polyposis coli (p < 0.05). Only 2 patients with polyposis coli
      were treated by colectomy. Histopathology included juvenile polyp (95%),
      inflammatory pseudopolyp (2.5%), and hyperplastic polyp (2.5%). CONCLUSION: Most
      of the children with colorectal polyp had juvenile polyp that is commonly found
      in the rectosigmoid colon. However, a significant number of patients had carrying
      polyps proximal to the rectosigmoid region, which would be easily missed by
      sigmoidoscopy. With the concern of malignancy change particularly in children
      with polyposis coli, routine colonoscopy should be considered as an initial
      investigation in children with colorectal polyp.

PMID- 14971534
TI  - Accuracy of transvaginal ultrasound for the evaluation of myometrial invasion in
      endometrial carcinoma.
AB  - OBJECTIVE: To evaluate the accuracy of transvaginal ultrasound for the evaluation
      of myometrial invasion in endometrial carcinoma in comparison with standard
      paraffin section. METHOD: A total of 111 patients with endometrial carcinoma
      diagnosed from fractional curettage underwent pre-operative transvaginal
      ultrasonography to assess myometrial invasion. Operation for surgical staging was
      subsequently performed and the hysterectomy specimen was evaluated for depth of
      myometrial invasion by standard paraffin section blinded from transvaginal
      ultrasound results. Final histopathologic diagnosis and depth of myometrial
      invasion were obtained from standard paraffin section. Ultrasonographic
      assessment was compared with the histopathological results. RESULTS: In
      evaluation of myometrial invasion, transvaginal ultrasound yielded the
      sensitivity of 69.4 per cent, specificity of 70.6 per cent, positive predictive
      value of 53.2 per cent, negative predictive value of 82.8 per cent, and accuracy
      of 70.3 per cent. The accuracy, sensitivity, specificity, negative predictive
      value, false positive and negative rates were comparable between grade 3 and
      grade 1 and 2 tumors. However, the positive predictive value was significantly
      higher among grade 3 than grade 1 and 2 tumors. The Kappa coefficients were 0.57
      and 0.22 for grade 3 and grade 1 and 2 tumors respectively. CONCLUSION:
      Transvaginal ultrasound for assessment of depth of myometrial invasion in
      endometrial carcinoma provided acceptable accuracy compared with standard
      paraffin section. This technique might be of value for the decision making in the
      intra-operative management of endometrial carcinoma.

PMID- 14971535
TI  - Penetrating keratoplasty following scleral patch graft procedure.
AB  - PURPOSE: To present the benefit of preserved sclera for immediately repairing
      perforated corneal ulcer and report the clinical outcome of patients undergoing
      penetrating keratoplasty after scleral patch graft. PATIENTS AND METHOD: The
      results of perforated corneal ulcer patients, who underwent penetrating
      keratoplasty after scleral patch graft between January 1996 and December 2002,
      were reviewed retrospectively. The causes of the corneal ulcer were also
      included. RESULTS: Penetrating keratoplasty was performed after scleral patch
      graft for perforated corneal ulcer on four patients, three males and one female.
      The culture results from corneal scraping showed Fusarium spp in two cases and
      Streptococus pneumoniae in one. One patient had a presumed bacterial corneal
      ulcer. The post-penetrating keratoplasty visual acuity ranged from hand motions
      to 20/40. CONCLUSION: The scleral patch graft procedure for perforated corneal
      ulcer may benefit in circumstances of unavailable corneal donors. The results of
      penetrating keratoplasty after scleral patch graft were favorable.

PMID- 14971536
TI  - Maternal knowledge, attitude and practice of safety belt use during pregnancy at
      Srinagarind Hospital.
AB  - From January 2002 to July 2002, 260 pregnant women of more than 20 weeks
      gestation at the antenatal care unit of Srinagarind Hospital, who fulfilled the
      criteria and had signed consent forms, and had answered the structured
      questionnaires. This cross sectional study showed that 230 women (88.5%) had an
      acceptable level of knowledge. Only 85 pregnant women (32.7%) had received
      information about safety belt use during pregnancy and mostly from books or
      magazines. There were 97, 154, and 9 pregnant women (37.3%, 59.2%, and 3.5%) who
      had a good, fair and poor attitude about safety belt use during pregnancy.
      Prevalence of safety belt use during pregnancy was 93.5 per cent and 17 pregnant
      women (6.5%) never used it during pregnancy. The most frequent reason for not
      wearing safety belt was discomfort. Two hundred and twenty pregnant women (90.5%)
      identified the correct position of safety belt use.

PMID- 14971537
TI  - Meshed skin graft versus split thickness skin graft in diabetic ulcer coverage.
AB  - OBJECTIVE: To compare results of skin graft healing in diabetic ulcers between
      the meshed skin graft method and split thickness skin graft method. Duration of
      complete skin graft healing in both groups was recorded. The relations between
      ulcer size and complete skin graft healing duration were analyzed. PATIENTS AND
      METHOD: This research used a prospective randomized controlled study with 80
      diabetic ulcer patients from January 2002-June 2003. Thirty-eight cases were
      treated by the meshed skin graft method with expansion ratio 1:3 and another 42
      cases were treated with the ordinary split-thickness skin. RESULTS: The means of
      complete healing duration were 19.84 +/- 7.37 days in the meshed skin group and
      20.36 +/- 7.21 days in the normal split-thickness skin graft group. There was no
      statistically significant difference between the groups in duration of complete
      graft healing and efficacy of treatment. The cosmetic result was accepted in both
      skin graft methods. There was no statistically significant difference between
      wound size and complete skin graft healing duration. CONCLUSION: The meshed skin
      graft method is as good for diabetic ulcer coverage as the ordinary split
      thickness skin graft.

PMID- 14971538
TI  - A comparison of the efficacy of cisatracurium and atracurium in kidney
      transplantation operation.
AB  - Cisatracurium is a new intermediate-acting benzylisoquinolinium neuromuscular
      blocking agent that is one of the ten stereoisomers contained in atracurium
      besylate. Atracurium is known to be the muscle relaxant of choice in end stage
      renal disease patients. This study aimed to compare the efficacy of cisatracurium
      and atracurium in the aspect of intubation and maintenance dosages, hemodynamic
      response after intubation and cost effectiveness between the two agents in kidney
      transplant patients. MATERIAL AND METHOD: From August 2001 to July 2002, 46 end
      stage renal disease patients obtained kidney transplantation operation under
      general anesthesia with 50:50 N2O:O2, fentanyl, isoflurane anesthesia. Tracheal
      intubation and maintenance of muscle relaxant with each drug were administered in
      23 of each group-atracurium as control (C) while cisatracurium was the study (S)
      group. RESULTS: There was no difference in the demographic data of the 2 groups-
      13 males/10 females in the S group and 11 males/12 females in the C group. Eighty
      seven per cent in the S group underwent living-related kidney transplantation
      operation, with 55.56 per cent in the C group. Most of the donors were siblings,
      i.e. 42.11 per cent in the S group and 46.67 per cent in the C group. The mean
      dosage for intubation in the S group was 0.17 +/- 0.02 mg/kg and 1.25 +/- 0.49
      microg/kg/min for maintenance. The mean dosage for intubation in the C group was
      0.64 +/- 0.07 mg/kg and the mean maintenance dose was 5.38 +/- 0.83
      microg/kg/min. In both groups there was no statistical difference in hemodynamic
      changes. One patient in the S group received calcium channel blocker to reduce
      blood pressure before induction of anesthesia, while 2 patients in the C group
      were given nifedipine 5 mg before induction. Although the cisatracurium cost was
      higher than atracurium, from the cost-minimization analysis, it turned out to be
      lower per case. CONCLUSION: This study demonstrated the efficacy of cisatracurium
      in hemodynamic stability and safety in kidney transplantation operations. In
      spite of the more costly price, cisatracurium is beneficial in some end stage
      renal disease (ESRD) patients with coronary artery disease who need very stable
      hemodynamics.

PMID- 14971539
TI  - Evaluation of the sensitivity of the double-contrast upper gastrointestinal
      series in the diagnosis of gastric cancer.
AB  - OBJECTIVE: To evaluate the sensitivity, specificity and accuracy of the double
      contrast upper gastrointestinal series (UGI series) in the diagnosis of gastric
      cancer. MATERIAL AND METHOD: The authors retrospectively reviewed the radiographs
      of the double-contrast UGI series for diagnosis of gastric cancer of 84 patients
      who had pathological confirmation by gastric biopsies and/or operations. RESULTS:
      The lesions were true positive in 45 patients, true negative in 28 patients,
      false positive in 8 patients and false nagative in 3 patients. The authors found
      pathologically proved gastric cancers in 48 patients. They were 42
      adenocarcinomas (87.5%), 3 gastric mucosa-associated lymphoid tissue lymphomas
      (6.2%), one gastrointestinal stromal tumor (2.1%), one squamous cell carcinoma at
      the distal esophagus involving the cardia (2.1%) and one cancer of the pancreatic
      head with invading gastric antrum (2.1%). The sensitivity, specificity and
      accuracy of the present study were 93 per cent, 77 per cent and 86 per cent,
      respectively. They showed small differences compared to the previous studies.
      CONCLUSION: The present findings indicate that the double-contrast UGI series has
      high sensitivity, specificity and accuracy. It should be considered a sensitive
      technique and initial examination in the diagnosis of gastric cancer.

PMID- 14971540
TI  - LacCur stain for detection of mucin in adenocarcinoma.
AB  - Identification of cytoplasmic mucin, usually by Mayer's mucicarmine stain, is one
      of the criteria to diagnose adenocarcinoma. The inexpensive LacCur stain, made up
      of Curcuma longa (khamin-shan) and secreta of Laccifer lacca (krang) has been
      introduced. The aim of this study was to compare the Mayer's mucicarmine and
      LacCur stains in the detection of mucin material. The specimens included 17
      adenocarcinomas of the stomach, 16 of the colon, 18 of the lung, 16 of the
      breast, and 12 of the bile duct. Squamous cell carcinoma and hepatocellular
      carcinoma (altogether 20 cases) were set as negative control. Like Mayer's
      mucicarmine, LacCur was capable of detecting of intracytoplasmic mucin in all
      adenocarcinomas of the stomach, colon and bile duct, and revealed mucin substance
      in 15/18 and 11/16 cases of specimens from the lung and breast, respectively. The
      negative control group showed a negative result. Although a little more time
      required in preparation, the LacCur stain is simple and very economical.

PMID- 14971541
TI  - Candida species, genotypes and antifungal susceptibility of Candida isolates from
      blood samples of patients at the largest tertiary care hospital in Thailand
      during 1999-2002.
AB  - From 1999 to 2002, a total of 202 Candida isolates causing candidemia were
      recovered from 202 individual patients in the largest tertiary hospital in
      Bangkok, Thailand. C. albicans comprised 44.55 per cent of all isolates. Non
      albicans Candida spp. isolates accounted for 55.45 per cent of all candidemia
      episodes and were primarily due to C. tropicalis (45%) followed by C.
      parapsilosis (6%), C. glabrata (4%), and C. krusei (0.5%). Non-albicans Candida
      spp appeared more frequently in children (59%). Regarding etiology, non-albicans
      Candida spp showed an increase (67%) in the year 2002. The distribution of C.
      albicans genotypes was as follows: genotype A, 71 per cent; genotype B, 26 per
      cent and genotype C, 3 per cent, with a similar susceptibility proportion to
      amphotericin B, fluconazole and itraconazole. All isolates of C. albicans, C.
      tropicalis, and C. parapsilosis were susceptible to fluconazole in vitro. Only
      16.7-19.8 per cent of the isolates were resistant to itraconazole. A high
      proportion of C. glabrata isolates showed drugs resistance.

PMID- 14971542
TI  - Intra-articular injection of deproteinized hemodialysate in osteoarthritis of the
      knee: a case-series.
AB  - OBJECTIVE: To report the efficacy of intra-articular injection of deproteinized
      hemodialysate including its side effects in a case-series of knee osteoarthritic
      (OA) patients. MATERIAL AND METHOD: Intra-articular injection of deproteinized
      hemodialysate was performed in 17 subjects (3 male and 14 female) with primary
      knee OA. Their average age was 63 years (min, max = 50, 80 yrs). The X-ray
      appearance was grade II-III according to Kellgren-Lawrence criteria.
      MEASUREMENTS: 100 mm visual analogue scale (VAS) and any side effects. RESULTS:
      The mean (95% CI) of the VAS before and after injection were 70.0 (59.9-80.1) and
      42.7 (31.2-54.2) respectively, with a p-value of < 0.001. The mean difference in
      pain score was 27.35 (95% CI = 17.0-37.7). The symptoms of knee pain resolved in
      an average of 4.8 (2.9) days (min, max = 1, 10). No side effects were found.
      CONCLUSION: Intra-articular injection of deproteinized hemodialysate is effective
      and safe. However, a further controlled trial with an adequate sample size should
      be performed to confirm the efficacy as well as to detect any adverse effects of
      this drug.

PMID- 14971543
TI  - Squamous cell carcinoma of the lacrimal sac: a case report.
AB  - Lacrimal sac tumors are rare tumors of the periorbital region. The authors report
      a case of squamous cell carcinoma of the lacrimal sac in a 47-year-old Thai man.
      The patient presented with epiphora and a palpable mass in the medial canthal
      area. The diagnosis was confirmed by the pathological studies. Radical surgery
      and radiation therapy were given. Early detection and long-term follow-up are
      necessary.

PMID- 14971544
TI  - Difficulties on ethics in medical practice.

PMID- 14971545
TI  - Revisiting commitment.

PMID- 14971546
TI  - Sjogren's syndrome.

PMID- 14971548
TI  - Limited obstetric ultrasound examinations.

PMID- 14971549
TI  - Spinal muscular atrophy in the neonate.
AB  - Spinal muscular atrophy (SMA) type I is an autosomal recessive disorder
      characterized by loss of lower motor neurons in the spinal cord. This severe
      hereditary neurodegenerative disorder is an important cause of morbidity in the
      neonate and the leading hereditary cause of infant mortality. The characteristic
      degeneration of anterior horn cells in the spinal cord leads to progressive
      muscular weakness and atrophy of the skeletal muscles. In SMA type I, the most
      severe form of SMA, death usually ensues by 2 years of age from respiratory
      failure or infection. Accurate diagnosis is now available through genetic
      testing, and progress is being made toward the development of therapy based on
      understanding of the disease mechanism. The neonatal nurse plays a pivotal role
      in identifying and caring for these medically fragile infants and in providing
      support and education for parents and families.

PMID- 14971550
TI  - Calcium in women: healthy bones and much more.
AB  - Osteoporosis is one of the leading health problems of women today, and the
      expectation is that more than 41 million women worldwide will be affected within
      the next 20 years if current trends are not reversed. Prevention of osteoporosis
      must be a focus for nurses, rather than merely the treatment of the problem. The
      majority of bone mass is developed during the adolescent and young adulthood
      years, with nearly 90% of skeletal mass accumulated by age 18. Current research
      has demonstrated that young women's intake of calcium is significantly below the
      recommended dietary intake. This article reviews the role and functions of
      calcium, how it is transported, and factors that may significantly increase or
      impair the absorption of this macronutrient. Strategies are described that will
      assist nurses in assessing the patient's diet and making appropriate
      recommendations regarding the intake of calcium and other micronutrients. A more
      in-depth and thorough understanding of this important mineral will enable nurses
      to strengthen their knowledge and confidence in helping patients and themselves
      change the focus from treating the disease to the improvement and maintenance of
      healthy bones and the prevention of other health conditions in women.

PMID- 14971551
TI  - The future of professional education in natural family planning.
AB  - Nurses and other health care professionals often have little knowledge of methods
      of natural family planning (NFP) and do not readily prescribe natural methods for
      their patients. One reason for this is that little or no information on NFP is
      provided in nursing or medical schools. The holistic, informational, and
      integrative nature of NFP fits well with professional nursing practice. A
      university online distance education NFP teacher training program, which offers
      academic credit and includes theory, practice, and the latest developments in
      fertility monitoring, has been developed for health care professionals.
      Professional NFP services in the United States need to meet worldwide standards
      and include documenting and assessing pregnancy outcomes, tailoring NFP services
      to the client or couple, and simplifying them for ease of use in a standard
      health care practice.

PMID- 14971552
TI  - A model for the HELLP syndrome: the maternal experience.
AB  - OBJECTIVE: To describe the experience of mothers whose pregnancies were
      complicated with HELLP syndrome (hemolysis, elevated liver enzymes, and low
      platelets) and to determine if such experiences could be clustered by common
      themes from which a model could emerge. DESIGN: Retrospective, descriptive,
      qualitative study utilizing grounded theory analysis. SETTING: Participants were
      interviewed in their homes via telephone. Participants were from Kansas, Maine,
      Maryland, Michigan, Minnesota, Mississippi, South Carolina, Utah, and Wyoming,
      representing both urban and rural settings. PARTICIPANTS: Nine self-selected
      survivors of HELLP syndrome. RESULTS: The essential structure of the experience
      of HELLP syndrome can be expressed as a circle of no control and not knowing,
      which included the five themes of premonition, symptoms, betrayal, whirlwind, and
      loss. The pervading emotions expressed were fear (of death), frustration, anger,
      and guilt. HELLP syndrome represents a unique maternal experience that can be
      expressed in a model.

PMID- 14971553
TI  - Prenatal predictors of intimate partner abuse.
AB  - OBJECTIVE: To determine the prevalence of physical abuse and to identify
      predictors of abuse in a sample of pregnant women in Alabama. DESIGN: A
      prospective, correlational design was used. SETTING: Participants were drawn from
      four unrelated public and private prenatal clinics in Tuscaloosa, Alabama.
      PARTICIPANTS: The sample consisted of pregnant women between 20 and 34 years of
      age who had no high-risk health conditions and who initiated prenatal care during
      the 1st trimester. Four hundred thirty-nine ethnically diverse women completed
      interviews during the 1st and 3rd trimesters and had available birth outcomes.
      MAIN OUTCOME MEASURE: Physical abuse during pregnancy was measured by a modified
      version of the Abuse Assessment Screen. Bivariate and multiple logistic
      regressions yielded significant associations between individual predictors and
      physical abuse during pregnancy. RESULTS: The findings showed that 10.9% of the
      sample experienced physical abuse during the current pregnancy and 62% reported
      the intimate partner or former intimate partner to be the perpetrator. The best
      predictive model included stressful life events, depression, lack of faith in God
      or a higher power, and lack of contraceptive use.

PMID- 14971554
TI  - Parents' perspectives on decision making after antenatal diagnosis of congenital
      heart disease.
AB  - OBJECTIVE: To discover and describe how prospective parents make decisions when
      they learn of their baby's congenital heart disease (CHD) during pregnancy, and
      to provide professionals with direction for their interactions with these
      families. DESIGN AND METHOD: Qualitative analysis informed by symbolic
      interactionism. SETTING: A tertiary care women's health center that provided
      referral services for a province with a population of 4 million. PARTICIPANTS:
      Mothers and fathers of 19 babies with antenatally diagnosed CHD participated in
      interviews during pregnancy and after the birth of their baby. Thirty-four
      interviews were analyzed for common themes and distinguishing characteristics of
      antenatal decision making. RESULTS: Parents approached their antenatal decisions
      regarding further testing and continuation of the pregnancy as their first
      parenting decisions. They made their decisions with differing degrees of apparent
      ease or deliberation, and some parents more readily sought the opinion of
      professionals. The offered opinions offended some parents, even though the
      professionals may have intended the information as descriptive of options, not
      suggestive of a particular decision. CONCLUSION: Although advances in technology
      have enabled diagnosis of CHD antenatally, health care professionals, including
      nurses, must elicit each parent's particular perspective, be cognizant of their
      professional influence, and actively support parents from the time of the
      antenatal diagnosis.

PMID- 14971555
TI  - More than just menstrual cramps: symptoms and uncertainty among women with
      endometriosis.
AB  - OBJECTIVE: To examine the frequency, severity, interference with daily life, and
      symptom distress associated with endometriosis and to explore the relationships
      among symptoms, emotional distress, uncertainty, and preference for and adequacy
      of information. DESIGN: A descriptive, cross-sectional correlational study.
      SETTING: Data were collected at a conference of the Endometriosis Association in
      Milwaukee, Wisconsin. PARTICIPANTS: A convenience sample of 298 women attending
      an educational program. MAIN OUTCOME MEASURES: Endometriosis symptoms and symptom
      distress, emotional distress, and adequacy of information were assessed using
      author-developed scales. Preference for information was measured by a revision of
      the Krantz Health Opinion Survey Information Subscale. Uncertainty was assessed
      using the Mishel Uncertainty in Illness Scale-Community Form. RESULTS: Women
      experienced multiple symptoms associated with varying levels of distress,
      including symptoms not typically associated with endometriosis. Participants
      sought out information but were undecided about whether they had sufficient
      information about the disease. Uncertainty about endometriosis was relatively
      high and associated with emotional distress and lack of information about the
      disease. CONCLUSIONS: Reported symptoms demonstrate the complexity and impact of
      endometriosis. Women's preference for information and experience of emotional
      distress and uncertainty suggest the need for information and support.
      Prospective, controlled studies on the impact of endometriosis and interventions
      to inform and support patients are needed.

PMID- 14971556
TI  - Giving birth: the voices of Orthodox Jewish women living in Canada.
AB  - OBJECTIVE: To describe the meaning of the childbirth experience to Orthodox
      Jewish women living in Canada. DESIGN: In this phenomenologic study, audiotaped
      interviews were conducted. Tapes were transcribed verbatim and analyzed for
      emergent themes. Demographic data also were collected. SETTING AND PARTICIPANTS:
      Thirty Orthodox Jewish women who had given birth to healthy full-term newborns at
      a university-affiliated Jewish hospital in Montreal, Canada, participated in the
      study. Data were collected within 2 weeks after childbirth, either in the
      mother's postpartum hospital room or in her home. RESULTS: The following themes
      reflecting spiritual/cultural dimensions of the childbirth experience were
      identified: (a) birth as a significant life event, (b) birth as a bittersweet
      paradox, (c) the spiritual dimensions of giving birth, (d) the importance of
      obedience to rabbinical law, and (e) a sense of support and affirmation.
      CONCLUSION: This study documents cultural, religious, and spiritual dimensions of
      the childbirth experience of Orthodox Jewish women living in Canada. Knowledge
      and appreciation of the multiple dimensions of childbirth reflected by this
      study's findings can contribute to holistic and culturally competent nursing care
      of women and newborns.

PMID- 14971557
TI  - Resources for evidence-based practice, January/February 2004.

PMID- 14971558
TI  - Maternal or fetal heart rate? Avoiding intrapartum misidentification.
AB  - Electronic fetal monitoring technology is capable of monitoring and recording
      maternal heart rate (MHR) patterns that mimic fetal heart rate (FHR) patterns.
      The ability to distinguish one from the other requires knowledge of FHR and MHR
      characteristics and monitoring technology. Application of this knowledge may
      prevent fetal injury and death. This article reviews heart rate monitoring
      technology and the similarities and differences between MHR and FHR baselines,
      accelerations, and decelerations. Three case reports are described in which the
      MHR was mistaken for the FHR prior to the diagnosis of fetal demise. Guidelines
      to confirm fetal life and prevent misidentification are proposed.

PMID- 14971559
TI  - VBAC: safety for the patient and the nurse.
AB  - During the 1970s and 1980s, some women fought for the opportunity to deliver
      vaginally after a cesarean birth (VBAC). The American College of Obstetricians
      and Gynecologists initially supported VBAC for many low-risk women. Interventions
      increased and complications of VBAC were reported, however, and recommendations
      changed. VBAC should be performed in hospitals equipped to care for women at high
      risk. Nurses caring for patients undergoing VBAC should be able to recognize and
      respond to the signs and symptoms of uterine rupture, including the most common
      symptom, which is a nonreassuring fetal monitor tracing. Nurses also should be
      aware of the necessity for 24-hour blood banking, electronic fetal monitoring, on
      site anesthesia coverage, and continuous presence of a surgeon.

PMID- 14971560
TI  - Malpractice and the neonatal intensive-care nurse.
AB  - Perinatal nursing has become a specialty vulnerable to litigation, due to
      parents' high expectations of health care providers' ability to monitor for
      adverse events and intervene appropriately to prevent harm. When a neonate is
      injured during the perinatal period, a frequent response is to look for someone
      to blame. Neonatal nursing is considered a specialty area, requiring specialized
      knowledge and training. By adhering to recognized and accepted internal and
      external policies, neonatal nurses will uphold the standard of care set for their
      area of practice and avoid legal liability.

PMID- 14971561
TI  - Liability in the care of the elderly.
AB  - The most common reasons nursing homes are sued are residents' fractures and
      pressure ulcers. The majority of cases in a sample of 118 nursing home lawsuits
      resulted in settlement or a plaintiff winning at trial. The most successful
      method of defending a lawsuit was to dispute the facts. Risk prevention
      strategies include working in a sufficiently staffed facility, attending to the
      needs of the residents and families, and complying with federal and state
      regulations.

PMID- 14971563
TI  - Laser and proton radiation to reduce uveal melanoma-associated exudative retinal
      detachments.
AB  - PURPOSE: To assess whether laser-induced hyperthermia in conjunction with proton
      irradiation of choroidal melanoma may more rapidly decrease exudative retinal
      detachments. DESIGN: Case-control study. METHODS: This was a single-center
      prospective phase 1 study of choroidal melanoma patients with exudative retinal
      detachments. These tumors did not overhang the optic disc, involve the fovea, or
      have greater than 40% involvement of the ciliary body. Patients were treated with
      laser-induced hyperthermia and proton radiation; results were compared with those
      of similar patients treated at the same institution with only proton radiation.
      Patients were followed up in an identical manner for loss of subretinal fluid,
      visual acuity change, and visual field alterations. RESULTS: All 11 patients
      treated with combined laser and proton therapy had resorption of subretinal fluid
      with a mean duration of retinal detachment of 193 days, compared with 263 days in
      the group treated with only proton therapy (P<.04). At 1 year, visual acuity was
      similar in both groups. CONCLUSIONS: Combined laser-induced hyperthermia and
      proton radiation may dissipate exudative detachments more rapidly than radiation
      alone.

PMID- 14971562
TI  - Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein
      inducer, in a rat glaucoma model.
AB  - PURPOSE: To study the effects of geranylgeranylacetone (GCA) on the expression of
      inducible (HSP72) and constitutive (HSC70) heat shock proteins (HSPs) on retinal
      ganglion cells (RGCs) in a rat model of glaucoma. METHODS: Adult Wistar rats were
      given intraperitoneal injections of GGA, 200 mg/kg daily. Western blot analysis
      and immunohistochemical staining for HSP72 and HSC70 were performed after 1, 3,
      and 7 days of GGA administration. After 7 days of GGA pretreatment, intraocular
      pressure (IOP) was elevated unilaterally by repeated trabecular argon laser
      photocoagulation 5 days after intracameral injection of india ink. After the
      first laser photocoagulation, CGA was given twice a week. RGC survival was
      evaluated after 5 weeks of IOP elevation. Immunohistochemistry and TdT-mediated
      biotin-dUTP nick end labeling (TUNEL) were performed after 1 week of IOP
      elevation. Quercetin, an inhibitor of HSP expression, was also administered to a
      separate group. RESULTS: There was increased expression of HSP72 in RGCs at 3 and
      7 days after GGA administration, but HSC70 was unchanged. After 5 weeks of IOP
      elevation, there was 27% +/- 6% loss of RGCs. The administration of GGA
      significantly reduced the loss of RGCs, lessened optic nerve damage, decreased
      the number of TUNEL-positive cells in the RGC layer, and increased HSP72.
      Quercetin administration abolished these protective effects. CONCLUSIONS: These
      results demonstrate that systemic administration of GGA protects RGCs from
      glaucomatous damage in a rat model and suggest a novel pathway for
      neuroprotection for patients with glaucoma.

PMID- 14971564
TI  - Unoperated eyes with persistent fetal vasculature.
AB  - PURPOSE: To present a follow-up on children with persistent fetal vasculature
      (PFV) when surgery was not performed. METHODS: From January 1992 through June
      2001, 31 infants (31 eyes) with PFV were evaluated to document the number of eyes
      operated on versus eyes not operated on to determine whether the latter group
      remained stationary or became worse. RESULTS: Seventeen of the 31 eyes underwent
      surgery. Of the 14 eyes not undergoing surgery, 7 were judged to be inoperable.
      The remaining 7 eyes were not operated on because the fundus could be visualized
      through an undilated pupil. Follow-up on 5 of the 7 eyes ranged from 18 months to
      9.5 years. None showed progression of the lens opacity or development of retinal
      detachment. The eyes were amblyopic but functional. CONCLUSIONS: In this limited
      series of eyes with PFV where the plaque was not large enough to fill the pupil,
      the eyes followed up were amblyopic, but useful vision was retained and the lens
      opacity did not enlarge.

PMID- 14971565
TI  - Graded full-thickness anterior blepharotomy for upper eyelid retraction.
AB  - PURPOSE: A chief morbidity of Graves' eye disease (GED) is upper lid retraction
      that results in exposure keratopathy and cosmetic deformity. This study was
      conducted to assess the efficacy of graded anterior blepharotomy to treat upper
      lid retraction. METHODS: Fifty eyelids of 32 patients with GED-associated upper
      lid retraction causing symptomatic ocular exposure were treated with graded,
      transcutaneous, full-thickness, anterior blepharotomy. Preoperative and
      postoperative ocular exposure symptoms, upper lid position, lagophthalmos, and
      keratopathy were compared. RESULTS: At an average of 8.5 +/- 8.1 months (range, 2
      to 35 months) follow-up, more than 90% of preoperative symptoms resolved or
      improved. Upper eyelid position (P < .00001), lagophthalmos (P < .0001), and
      keratopathy (P < .01) were significantly improved. Mild contour abnormalities
      (all < or = 1 mm) occurred in 7 of 50 eyelids. Eyelid crease recession or
      asymmetry occurred in 4 of 22 patients with postoperative lid crease
      measurements. Complications of ptosis, wound dehiscence, and full-thickness hole
      each occurred once. The average time for performing the procedure was 31.5 +/-
      8.9 minutes per eyelid. CONCLUSIONS: Graded anterior blepharotomy for upper lid
      retraction is a safe and highly effective surgical treatment for symptomatic GED
      associated upper eyelid retraction. This technique achieves excellent functional
      and cosmetic outcomes.

PMID- 14971566
TI  - Human RPE cell apoptosis induced by activated monocytes is mediated by caspase-3
      activation.
AB  - PURPOSE: To determine the effects of activated monocytes on the induction of
      human retinal pigment epithelial (HRPE) cell reactive oxygen metabolite (ROM)
      production and apoptosis. METHODS: HRPE cells were co-cultured with interferon
      gamma (IFN-gamma)-stimulated human monocytes. HRPE apoptosis was detected by
      propidium iodide, proliferating cell nuclear antigen (PCNA) and TdT-mediated dUTP
      nick end labeling (TUNEL) staining, caspase-3 activation, and Western blot
      analysis. HRPE cell ROMs were imaged using the fluorescent marker
      dihydrotetramethylrosamine (H2TMRos). RESULTS: IFN-gamma-activated monocytes in
      direct contact with HRPE cells elicited significant increases in TUNEL-positive
      (P < .0001) and decreases in PCNA-positive (P < .0001) HRPE cells. The activated
      monocytes also induced HRPE cell caspase-3 activation, which was inhibited by
      inhibitor Z-DEVD-fmk. Co-incubations, in which monocytes were either prevented
      from direct contact with HRPE cells or separated from HRPE cells after 30 minutes
      of direct contact, did not induce significant HRPE cell apoptosis. Anti-CD18 and
      anti-ICAM-1 antibodies significantly reduced activated monocyte-induced TUNEL
      positive HRPE cells, by 48% (P = .0051) and 38% (P = .046), respectively, and
      caspase-3 activity by 56% (P < .0001) and 45% (P < .0001), respectively. Overlay
      of monocytes induced HRPE cell ROM that was inhibited by anti-CD18 and anti-ICAM
      1 antibodies, but not by superoxide dismutase (SOD) or nitric oxide (NO)
      inhibitors. Accordingly, neither SOD nor NO inhibitors had significant effects on
      HRPE cell apoptosis or caspase-3 activation. CONCLUSIONS: We demonstrated that
      IFN-gamma-activated monocytes may induce ROM in HRPE cells through cell-to-cell
      contact, in part via CD18 and ICAM-1, and promote HRPE cell apoptosis via caspase
      3 activation. These mechanisms may compromise HRPE cell function and survival in
      retinal diseases in which mononuclear phagocyte infiltration at the HRPE
      interface is observed.

PMID- 14971567
TI  - Eosinophilic granuloma of the orbit: a paradox of aggressive destruction
      responsive to minimal intervention.
AB  - PURPOSE: To describe the findings and outcomes in eosinophilic granuloma
      (unifocal Langerhans cell histiocytosis [LCH]) of the orbit, and to explain the
      paradox of aggressive bone destruction responsive to minimal intervention.
      METHODS: Retrospective, consecutive, interventional case series of patients
      treated from 1985 through 2001. Minimum inclusion criteria were demonstration of
      CD1a positivity or Birbeck granules, treatment by a single surgeon, systemic
      evaluation by a pediatric oncologist, and follow-up of 12 months. A pathogenetic
      construct was assembled from general LCH concepts and the specific orbital
      findings. RESULTS: Seven patients met study criteria. All were male, 2 to 16
      years of age. All had eyelid or forehead swelling and osteolytic defects, with
      symptoms of 2 to 6 weeks' duration. All underwent incisional biopsy, with frozen
      section examination suggestive of LCH in 6 of 7 cases. The 2 earliest patients
      received low-dose irradiation after simple biopsy. The 5 most recent patients had
      subtotal curettage at the time of biopsy; 4 of 5 received simultaneous
      intralesional corticosteroid injection. In all cases, systemic evaluation showed
      no other focus of LCH, reossification was timely, and no local recurrence or
      additional focus was noted in follow-up of 1 to 17 years. CONCLUSIONS: Transient
      immune dysfunction may provoke the cytokine-mediated proliferation of pathologic
      Langerhans cells within the hematopoietic marrow of the anterolateral frontal
      bone. These cells cause osteolysis through elaboration of interleukin-1 and
      prostaglandin E2. Corticosteroids can inhibit the mediators. We recommend
      incisional biopsy, frozen-section provisional diagnosis, subtotal curettage,
      intralesional corticosteroid instillation, postoperative systemic evaluation, and
      long-term follow-up.

PMID- 14971568
TI  - A myopic shift in Australian Aboriginals: 1977-2000.
AB  - BACKGROUND/AIMS: The prevalence of myopia has been reported to have increased in
      a number of population groups. We compared the refraction of Australian
      Aboriginal adults in 2000 with data collected in 1977 to assess whether there had
      been a change in the prevalence of myopia. METHOD: Australian Aboriginal adults
      aged 20 to 30 years old were selected from Central Australian communities in
      2000. Refraction was determined by noncycloplegic autorefraction. This was
      compared to mydriatic retinoscopy data collected in 1977. "Observer trials" were
      undertaken to assess the comparability of noncycloplegic autorefraction
      measurements and cycloplegic retinoscopy. Spherical equivalence cylinder and
      spheric were determined for all right and left eyes and compared using an
      analysis of variance. RESULTS: A total of 128 adults (58 males, 70 females) were
      examined in 2000 and compared with 161 adults (107 males, 54 females) examined in
      1977. The mean spherical equivalent in 2000 was -0.55 D +/- 0.88 D and in 1977
      was +0.54 D +/- 0.81 D. The difference of -1.09 D was highly significant (F =
      126, P < .001). Intraclass correlation coefficients showed good agreement between
      noncycloplegic autorefraction and cycloplegic retinoscopy. Neither gender,
      schooling, nor diabetes was associated with an increased risk of myopia.
      CONCLUSIONS: There appears to have been a significant shift toward myopia in
      Australian Aboriginals between 1977 and 2000. The cause of this myopic shift is
      unknown but mirrors that observed in other populations in recent years.

PMID- 14971569
TI  - Rotatory nystagmus synchronous with heartbeat: a treatable form of nystagmus.
AB  - PURPOSE: To describe a treatable form of nystagmus. METHODS: Two patients
      recently evaluated at the Mayo Clinic had experienced various forms of
      oscillopsia, imbalance, and worsening symptoms with a Valsalva maneuver. Close
      inspection of the eye revealed a subtle rotatory nystagmus that was synchronous
      with the heartbeat. RESULTS: The two patients had surgical treatment for
      dehiscence of the superior semicircular canal; postoperatively, their symptoms
      completely resolved. This is a relatively newly discovered condition that has not
      been described on either slit-lamp or ophthalmoscopic examination. The cause is
      related to a dehiscence of the superior semicircular canal that permits
      communication of variable pressures between the intracranial cavity and the
      perilymphatic spaces of the semicircular canal. CONCLUSION: Being aware of this
      unusual form of nystagmus may permit physicians to diagnose it--one of the few
      treatable forms of nystagmus.

PMID- 14971570
TI  - Histopathologic features of trabeculectomy surgery.
AB  - PURPOSE: Trabeculectomy surgery is the most common operative procedure for the
      treatment of medically uncontrolled glaucoma. Variability exists in both the
      design and the position of the limbal wound as well as in outcomes, even in cases
      with similarly designed wounds. The purpose of this study is to describe the
      histologic features of the surgical site of human eyes received at a pathology
      laboratory that had undergone trabeculectomy surgery and then attempt to explore
      possible associations of these features with success or failure of surgery.
      METHODS: We examined 64 autopsy and enucleated eyes of 53 patients obtained at
      the Eye Pathology Laboratory, Wilmer Eye Institute, Baltimore, Md, between
      January 16, 1974, and November 15, 1999. Examined aspects included the position,
      dimensions, and depths of the trabeculectomy site; features at the internal
      opening; and the inclusion of trabecular meshwork in the internal resection. An
      attempt was also made to judge the success of the trabeculectomy by a comparison
      of preoperative and postoperative intraocular pressures. RESULTS: Of all the
      histopathologic features examined, there was a statistical difference between the
      success and failure groups in only the presence of a cleft and the location of
      the posterior incision. CONCLUSIONS: The main finding of this study is that there
      is a large degree of variability in the size, position, and pathologic features
      of trabeculectomy sites. Features that can be avoided with the initial surgical
      approach, particularly a posterior resection posterior to the scleral spur, may
      increase the chance of surgical failure.

PMID- 14971571
TI  - The "demise" of diagnostic and research ocular pathology: temporary or forever?
AB  - PURPOSE: Several authorities have documented a significant decrease in support
      for modern eye pathology/pathology research laboratories. Indeed, many
      laboratories have closed or suffered marked cutbacks. The purpose of this report
      is to ask why this is so and to seek a possible means for reversing this trend.
      METHODS: Observations from the senior author's experience and a case from
      author's facility are analyzed. RESULTS: There are several reasons for ocular
      pathologists' difficulties, such as financial problems, lack of vision,
      personality conflicts, and problems with the departmental administration. Until
      recently, most research and development in several subspecialty fields of
      ophthalmology, including biodevices research, has been done primarily by
      engineers and in-house workers in industry. This precludes proper independent,
      nonbiased control and guidance from academia. Most ocular pathologists have not
      participated in this relatively new and wide-open field. CONCLUSIONS: We suggest
      a new realm of activity for today's newly trained ocular pathologists. Based on
      personal experience of two decades of fruitful collaboration with industry, we
      believe that ocular pathologists are uniquely trained to apply their expertise to
      various new fields of research that most pathologists today have not utilized. An
      important example is research on clinicopathological aspects of implantable
      biodevices. In addition, support and oversight should be provided by the major
      ophthalmic societies, such as the American Academy of Ophthalmology, in order to
      retain (even regain) control over this field. This is mandatory in order to
      control the safety and efficacy of new drugs and devices being introduced almost
      daily. Only then can clear differentiation between profit and patient welfare be
      achieved as potentially dangerous devices and techniques are let loose on the
      market. The field of "routine, descriptive" eye pathology is severely wounded and
      will return only in an attenuated fashion. In general, full-time support for
      ocular pathologists will not be possible unless they seek extra support from the
      private sector, engage in a concurrent clinical practice, or are supported by an
      endowed chair (a wonderful alternative).

PMID- 14971572
TI  - Presumed hyposecretory/hyperevaporative KCS: tear characteristics.
AB  - PURPOSE: To characterize patients with ocular surface drying and a diagnosis of
      keratoconjunctivitis sicca (KCS). METHODS: Patients with a prior diagnosis of KCS
      and symptoms of dryness or foreign-body sensation who also had vital staining of
      the interpalpebral fissure ocular surface in the absence of lid and ocular
      surface inflammation were entered into the study along with normal controls.
      Patients were segregated into those with "classic" KCS, who did not have
      concomitant meibomian gland dysfunction (MGD), and those with KCS and MGD. The
      latter had slit-lamp evidence of difficult-to-express or turbid meibomian
      secretions upon expression. Patients and normal controls were evaluated for tear
      volume, flow, and turnover using fluorophotometry; meibomian gland dropout by
      meibography; evaporation by evaporometry; and tear production by the Schirmer 1
      test. RESULTS: All patients with KCS had decreased tear volume, flow, and
      Schirmer 1 values as well as increased meibomian gland dropout. None of the
      patient groups were found to have increased tear evaporation compared with
      normals or other disease subgroups. No correlation between degree of meibomian
      gland dropout and evaporation was found. The degree of total vital staining or
      presence of corneal staining correlated with a more severe aqueous deficiency.
      CONCLUSIONS: Patients with ocular surface drying in the absence of inflammation
      have decreased tear volume, flow, and Schirmer 1 values as well as increased
      meibomian gland dropout. The role of meibomian gland dropout or slit-lamp MGD in
      disease is unclear and in our study specifically did not correlate with increased
      tear evaporation.

PMID- 14971573
TI  - Long-term study of accommodative esotropia.
AB  - PURPOSE: Previous studies of accommodative esotropia have been hampered by bias
      prone methods of data collection and analysis and by small sample size. The
      studies have conflicting conclusions, causing uncertain results. This study aims
      to determine long-term results of standard treatment of accommodative esotropia
      and identify predictors of outcome, while minimizing bias in data collection and
      analysis, using the largest possible sample size. METHODS: A research assistant
      collected data from all files of a large, long-established pediatric
      ophthalmology practice (M.M.P.). The assistant was given standardized collection
      forms that allowed inclusion of all patient data points over all visits. The
      assistant was masked as to study goals. She was instructed to include any patient
      with esotropia who had been prescribed glasses during treatment. Descriptive
      terms were converted to code numbers. A second, similarly masked research
      assistant entered data into a computerized database. Criteria for patient
      inclusion were designed to conform to earlier studies by I.H.L. and M.M.P. and
      were implemented by computer. RESULTS: The database totaled 1,307 patients
      (747,717 data points). Of these, 354 qualified for this analysis. A greater
      difference between near and distance esodeviation (AC/A relationship) correlated
      with a higher rate of deterioration of accommodative esotropia control (P<.0001).
      Deterioration also positively correlated with earlier age at onset, inferior
      oblique overaction, and amblyopia. CONCLUSIONS: This study agrees with our
      previous findings that a high AC/A relationship increases the likelihood of
      deterioration of accommodative esotropia, thus confirming the integrity of the
      database. This unique, unbiased dataset will be used for future analyses of
      esotropia.

PMID- 14971574
TI  - A mouse model of elevated intraocular pressure: retina and optic nerve findings.
AB  - PURPOSE: To develop and characterize a mouse model of elevated intraocular
      pressure (IOP) as a means to investigate the underlying cellular and genetic
      mechanisms of glaucomatous optic neuropathy. METHODS: An experimental increase in
      IOP was induced in one eye of each adult C57BL/6J mouse by argon laser
      photocoagulation of the episcleral and limbal veins. The IOP of both eyes of each
      mouse was measured using an indentation tonometer prior to treatment and once a
      week thereafter. The mouse retinal ganglion cells (RGCs) were identified
      immunocytochemically using an antiserum against Thy1,2, CD90.2, and the number of
      RGCs was measured with confocal microscopy. The reduction in the number of RGCs
      was compared in the experimental and control eyes. The mechanism of RGC death
      after IOP elevation was investigated using TdT-mediated dUTP nick end labeling
      (TUNEL) staining. The pathologic changes of optic nerve following elevated IOP
      were characterized by light and electron microscopy. RESULTS: After laser
      treatment, mean IOP was increased in the treated eyes from the control mean of 13
      +/- 1.8 mm Hg to 20.0 +/- 2.8 mm Hg at 4 weeks. Peak IOP was 32 +/- 2.5 mm Hg in
      the experimental group. RGC loss was 16.9% +/- 7.8% at 2 weeks (n = 6, P < .05)
      and 22.4% +/- 7.5% at 4 weeks (n = 6, P < .05) after laser photocoagulation.
      TUNEL staining showed that there were marked increases in the number of apoptotic
      nuclei in the ganglion cell layer in the treated eyes; moreover, these TUNEL
      positive cells were mostly distributed in the peripheral areas of the retina. The
      optic nerve axons from the eyes with elevated IOP were observed to demonstrate
      greater degeneration compared with the control group. CONCLUSIONS: The magnitude
      and duration of the elevation of the IOP supports the use of this model as a
      surrogate for glaucomatous optic neuropathy. The presumed apoptotic mechanism of
      RGC death is consistent with this assumption. Laser-induced increased IOP appears
      to be a viable means for future investigations of the genetic mechanisms of
      glaucoma.

PMID- 14971575
TI  - Retinal emboli and cardiovascular disease: the Beaver Dam Eye Study.
AB  - PURPOSE: To describe the 10-year incidence of retinal emboli, the associated risk
      factors, and the relationship of retinal emboli to stroke and ischemic heart
      disease mortality. METHODS: The Beaver Dam Eye Study (n = 4,926) is a population
      based study of persons 43 to 86 years of age. Retinal emboli were detected at
      baseline (1988-1990) and at a 5-year (1993-1995) and a 10-year (1998-2000) follow
      up by grading of stereoscopic 30 degrees color fundus photographs using
      standardized protocols. Cause-specific mortality was determined from death
      certificates. RESULTS: The 10-year cumulative incidence of retinal emboli was
      1.5%. While adjusting for age and sex, the incidence of retinal emboli was
      associated with increased pulse pressure (odds ratio [OR] 4th versus 1st quartile
      range, 2.42; 95% confidence interval (CI), 0.98-5.97; P test of trend = .03),
      higher serum total cholesterol (OR, 2.77; 95% CI, 1.06-7.23; P = .03), higher
      leukocyte count (OR, 2.28; 95% CI, 1.04-4.96; P = .05), smoking status (OR
      current versus never smoker, 4.60: 95% CI, 2.08-10.16; P < .001), and a history
      of coronary artery bypass surgery (OR, 7.17; 95% CI, 3.18-16.18; P < .001) at
      baseline. While controlling for age, sex, and systemic factors, a significantly
      higher hazard of dying with a mention of stroke on the death certificate was
      found in people with retinal emboli (hazard ratio, 2.40; 95% CI, 1.16-4.99)
      compared with those without. CONCLUSIONS: The data show an association of smoking
      and cardiovascular disease with the incidence of retinal emboli. Also, persons
      with retinal emboli are at increased risk of stroke-related death.

PMID- 14971576
TI  - Safety of intravitreal voriconazole: electroretinographic and histopathologic
      studies.
AB  - PURPOSE: Voriconazole, a novel triazole antifungal agent, presents potent
      activity against a broad spectrum of yeast and molds. To determine whether it
      could be safely used as an intravitreal agent in the treatment of fungal
      endophthalmitis, retinal toxicity of voriconazole was examined in a rodent animal
      model. METHODS: Voriconazole solutions were serially diluted and injected
      intravitreally into eyes of normal adult Sprague-Dawley rats so that the final
      intravitreal concentrations were 5 microg, 10 microg, 25 microg, 50 microg, and
      500 microg/mL (N = 3 for each concentration group). Saline was injected into the
      fellow eyes of each animal as controls. Three weeks after injections,
      electroretinograms (ERGs) were measured, and eyes were subsequently enucleated
      for histologic examination. RESULTS: In ERG studies, maximum scotopic b-wave,
      bmax intensity needed for half saturation, I0.5, and saturated a-wave amplitude
      were measured. There was no statistically significant difference in these
      parameters recorded between control eyes and voriconazole-injected eyes in any
      concentration groups. Histologic examination with light microscopy did not reveal
      any retinal abnormality in the eyes with 5 to 25 microg/mL intravitreal
      voriconazole. In the eyes with 50 microg/mL and 500 microg/mL voriconazole, small
      foci of retinal necrosis were occasionally observed in the outer retina,
      especially in the eyes with 500 mg/mL voriconazole. CONCLUSION: Our results
      demonstrate that intravitreal voriconazole of up to 25 mg/mL causes no ERG change
      or histologic abnormality in rat retina. This indicates that voriconazole is a
      safe antifungal agent that may be employed by intravitreal injection in the
      treatment of fungal endophthalmitis.

PMID- 14971577
TI  - Relationship of measures of frailty to visual function: the Beaver Dam Eye Study.
AB  - PURPOSE: To investigate the association of standard measures of frailty to visual
      acuity and contrast sensitivity. METHODS: Time to walk a measured course,
      handgrip strength, peak expiratory flow rate, ability to stand from a sitting
      position without using arms, best-corrected visual acuity, and contrast
      sensitivity were assessed at the third examination (1998-2000) of the Beaver Dam
      Eye Study. The study is population-based with the initial census in 1988-1990.
      RESULTS: All measures of frailty and vision were significantly associated with
      age (poorer function at older ages). In general, women had poorer function than
      men in each age category. An "index of frailty" consisting of highest quartile
      (slowest) gait time, lowest quartile of peak expiratory flow rate, lowest
      quartile of handgrip strength, and inability to stand from sitting in one try
      (for those not in a wheelchair) was constructed for women and men. A score of 0
      was the minimum amount of frailty, while a score of 4 indicated the maximum
      amount. Controlling for age, those with no evidence of frailty (score = 0) were
      likely to have the best visual acuity and best contrast sensitivity, while those
      with maximum evidence of frailty (score = 4) were likely to have poorest visual
      acuity and contrast sensitivity. CONCLUSION: Greater frailty was associated with
      poorer visual functions. Including a measure of visual function when assessing
      frailty may improve upon the usefulness of an index of frailty in predicting
      incidence of chronic systemic diseases and survival.

PMID- 14971578
TI  - Binocularity following surgical correction of strabismus in adults.
AB  - INTRODUCTION: This is a retrospective study to determine the preoperative and
      postoperative binocular status of adults who have undergone surgical correction
      of strabismus. METHODS: A list of all consecutive adult patients who underwent
      surgery for strabismus between June 1990 and December 2001 (surgery performed by
      M.B.M.) was compiled, and their medical charts were reviewed. Patients were
      included if their charts were available for review and if information on
      binocularity was recorded. Binocularity was measured by the Titmus stereo test,
      Worth 4-dot test, or synoptophore. Improvements or decreases in stereo acuity
      were noted 6 weeks postoperatively and at the final office visit. Prism
      management was incorporated preoperatively and/or postoperatively in some of our
      patients. A total of 112 patients underwent surgery for strabismus. Of these, 72
      patients, aged 16 to 80, were included; 24 were excluded because their charts did
      not contain any information on stereo acuity at least 6 weeks postoperatively or
      they were lost to follow-up after surgery, and 16 were excluded because their
      charts were unavailable from storage. RESULTS: A variety of surgeries were
      performed, the most common being a bilateral medial rectus recession. Eleven
      patients required a second surgery, and two required a third surgery. Overall, 30
      (42%) of the 72 patients improved in binocular function, 38 (53%) remained the
      same, and 4 (5%) had decreases in their stereo acuity. CONCLUSION: The benefits
      of surgical correction of strabismus in adults include improvement in binocular
      function, as seen in 42% of the patients in the study.

PMID- 14971579
TI  - Perioperative morbidity and mortality associated with vitreoretinal and ocular
      oncologic surgery performed under general anesthesia.
AB  - PURPOSE: To determine the incidence of postoperative systemic complications and
      nonophthalmic reasons for prolonged hospitalization after vitreoretinal
      procedures performed under general anesthesia. METHODS: Patient charts of
      vitreoretinal or ocular oncologic surgical cases performed under general
      anesthesia between 1996 and 2001 were reviewed retrospectively. Occurrences of
      postoperative systemic events within 4 weeks of surgery were documented. RESULTS:
      We identified 418 cases as having been performed under general anesthesia during
      the study period. The mean American Society of Anesthesiology physical status
      classification was 2.1. There were no confirmed cases of myocardial infarction
      (MI), pulmonary embolism (PE), or deep venous thrombosis (DVT) within the first
      24 hours after surgery. There were two instances of hospital admission for
      evaluation of postoperative chest pain (0.48%; 95% CI, 0.06-1.72), and four
      instances of hospital admission, or prolongation of stay, because of urinary
      retention (0.96%; 95% CI, 0.26-2.43). In the 4 weeks following surgery, there was
      one MI (0.24%; 95% CI, 0.01-1.33), 2 cases of nonfatal PE (0.48%; 95% CI, 0.06
      1.72), and 2 cases of DVT (0.48%; 95% CI, 0.06-1.72). All patients that developed
      PE and DVT had risk factors for the development of thromboembolic disease in
      addition to surgery under general anesthesia. CONCLUSIONS: In this study, 2.6% of
      cases had postoperative systemic complications after vitreoretinal or ocular
      oncologic surgery that was conducted under general anesthesia. Urinary retention
      was the most common reason for unanticipated hospital stay.

PMID- 14971580
TI  - Iris melanocyte numbers in Asian, African American, and Caucasian irides.
AB  - PURPOSE: The anatomical basis for iris color has long been a controversial issue
      in ophthalmology. Recent studies demonstrated that in Caucasians, blue-eyed, gray
      eyed, and hazel-eyed individuals have comparable numbers of iris melanocytes. The
      present investigation was carried out to compare melanocyte numbers in the irides
      of Asian, African American, and Caucasian brown-eyed individuals. METHODS:
      Paraffin-embedded sections from 71 brown-colored irides were incubated with
      rabbit anti-cow antibody against S100a, linked with an FITC conjugate antibody,
      and counterstained with Evans blue. Cells were counted under a fluorescence
      microscope and scored as melanocytes or other cells. Cell number, density, and
      iris area were calculated for each specimen. RESULTS: Caucasian and African
      American irides had comparable mean total melanocyte numbers. Asian irides had
      fewer total melanocytes than African American (P = .042) and Caucasian (P = .001)
      irides and smaller total number of cells (ie, melanocytes plus other cells) than
      African American (P = .054) or Caucasian (P = .009) irides. CONCLUSIONS: There is
      a statistically significant smaller mean total melanocyte number and mean total
      cellularity in Asian irides as compared to Caucasian and African American irides.
      This difference appears to be due to the combination of smaller iris area and
      lower melanocyte density in the Asian irides. The possibility exists that this
      may be a factor in ethnic variations in certain ocular diseases.

PMID- 14971581
TI  - The value of preoperative tests in the selection of blind patients for a
      permanent microelectronic implant.
AB  - PURPOSE: To determine the best candidates (ie, those requiring lowest current
      levels delivered to the retina to elicit visual perceptions) for long-term
      implantation of a microelectronic retinal implant through a series of
      preoperative visual, psychophysical, and electrophysiological tests. METHODS:
      This study protocol was granted an investigational device exemption by the Food
      and Drug Administration and was approved by the institutional review board at the
      University of Southern California. After informed consent was obtained, all
      subjects underwent the following preoperative tests: dark-adapted bright flash
      and 30-Hz flicker electroretinograms, electrical evoked responses (EERs) using a
      Burian-Allen corneal electrode to stimulate the globe, and psychophysical tests
      to evaluate the light and electrically elicited visual perceptions. Intraocular
      stimulation (IOS) of the retina was performed by an array of electrodes
      positioned on the internal limiting lamina. RESULTS: Lower vision correlated with
      less sensitive psychophysical responses (P<.0001). Lower vision and less
      sensitive psychophysical tests correlated with higher EER values for stimulus
      pulse widths of 2 ms (P<.0008) and 4 ms (P<.0002). Lower IOS currents correlated
      with more sensitive psychophysical responses (P<.02) and lower EER values at 4 ms
      (P<.04). CONCLUSIONS: Preoperative testing, especially psychophysical and
      electrophysiological tests to assess light and electrically driven visual
      responses, can help in evaluating patients for suitability for receiving a
      permanent microelectronic retinal implant. Further study is warranted.

PMID- 14971582
TI  - Medical malpractice predictors and risk factors for ophthalmologists performing
      LASIK and PRK surgery.
AB  - PURPOSE: To identify physician predictors in laser-assisted in-situ
      keratomileusis (LASIK) and photorefractive keratectomy (PRK) surgery that
      correlate with a higher risk for malpractice liability claims and lawsuits.
      METHODOLOGY: A retrospective, longitudinal, cohort study comparing physician
      characteristics of 100 consecutive Ophthalmic Mutual Insurance Company (OMIC)
      LASIK and PRK claims and suits to demographic and practice pattern data for all
      active refractive surgeons insured by OMIC between 1996 and 2002. Background
      information and data were obtained from OMIC underwriting applications, a
      physician practice pattern survey, and claims file records. Using an outcome of
      whether or not a physician had a prior history of a claim or suit, logistic
      regression analyses were used separately for each predictor as well as
      controlling for refractive surgery volume. RESULTS: Logistic regression analysis
      demonstrated that the most important predictor of filing a claim was surgical
      volume, with those performing more surgery having a greater risk of incurring a
      claim (odds ratio [OR], 31.4 for >1,000/year versus 0 to 20/year; 95% confidence
      interval [CI], 7.9 - 125; P = .0001). Having one or more prior claims was the
      only other predictor examined that remained statistically significant after
      controlling for patient volume (OR, 6.4; 95% CI 2.5 - 16.4; P = .0001). Physician
      gender, advertising, preoperative time spent with patient, and comanagement
      appeared to be strong predictors in multivariate analyses when surgical volume
      was greater than 100 cases per year. CONCLUSION: The chances of incurring a
      malpractice claim or suit for PRK or LASIK correlates significantly with higher
      surgical volume and a history of a prior claim or suit. Additional risk factors
      that increase in importance with higher surgical volume include gender,
      advertising, preoperative time spent with patient, and comanagement with
      optometrists. These findings may be used in the future to help improve the
      quality of care for patients undergoing refractive surgery and provide data for
      underwriting criteria and risk management protocols to proactively manage and
      reduce the risk of claims and lawsuits against refractive surgeons.

PMID- 14971583
TI  - Molecular pathology of primary intraocular lymphoma.
AB  - PURPOSE: To evaluate immunoglobulin heavy chain (IgH) gene rearrangements,
      cytokines and chemokines, and infectious agents in primary intraocular B-cell
      lymphoma (PIOL) cells, in order to better diagnose and understand PIOL. METHODS:
      We studied ocular specimens from 57 patients with PIOL at the National Eye
      Institute from 1991 to 2001. Specimens were analyzed for IgH gene rearrangements
      using microdissection and polymerase chain reaction (PCR). We measured vitreal
      interleukin (IL)-10 and IL-6 levels by enzyme-linked immunosorbent assay. IL-10
      mRNA was studied in PIOL cells using microdissection and reverse transcribed (RT)
      PCR. Chemokine and chemokine receptor expression was examined by using
      immunohistochemistry. Infectious DNA of human herpetic virus-8 (HHV-8), Epstein
      Bar virus (EBV), and Toxoplasma gondii was detected by using microdissection and
      PCR and was confirmed with Southern blot hybridization. RESULTS: IgH
      rearrangement(s) were demonstrated in all 50 tested cases. Cytokine levels were
      measured in the vitreous of 39 patients. Thirty-one had measurable cytokine
      levels: 24 of 31 had elevation of IL-10 relative to that of IL-6, and, in
      contrast, only 7 of 31 had elevation of IL-6 relative to IL-10. IL-10 mRNA was
      abundant in lymphoma cells of 6 examined cases. Lymphoma cells expressed
      chemokine receptors of CXCR4 and CXCR5 in three tested cases. HHV-8 DNA was found
      in 6 of 32 cases (18.8%), EBV DNA in 2 of 21 (9.5%), and T gondii DNA in 2 of 16
      (12.5%). CONCLUSIONS: Molecular analyses detecting IgH rearrangements and vitreal
      levels of IL-10 and IL-6 are useful adjuncts for PIOL diagnosis. A role for
      specific infectious agents is hypothesized in the pathogenesis of some cases of
      PIOL. B-cell chemokine is likely involved in attracting PIOL cells into the eye.

PMID- 14971584
TI  - Corneal wound healing after photorefractive keratectomy: a 3-year confocal
      microscopy study.
AB  - PURPOSE: To perform a sequential quantitative analysis of corneal wound healing
      after photorefractive keratectomy (PRK) by using confocal microscopy in vivo.
      METHODS: In a prospective, nonrandomized, comparative trial performed in an
      institutional setting, 24 eyes of 14 patients received PRK to correct refractive
      errors between -1.25 and -5.75 D. Central corneas were examined preoperatively
      and at 1 day, 5 days, and 1, 3, 6, 12, 24, and 36 months after PRK by using
      confocal microscopy. A masked observer randomly examined 3 to 6 confocal scans
      per eye per visit to determine epithelial and stromal thickness, keratocyte
      density in 5 anterior-posterior stromal layers, corneal nerve density in the
      subbasal region and the stroma, and corneal light backscattering (corneal haze).
      RESULTS: Epithelial thickness increased 21% (P < .001) by 12 months after PRK and
      thereafter remained unchanged to 36 months after PRK. There was no change in
      stromal thickness between 1 and 36 months after PRK (P = .35). The dense
      keratocyte population in the preoperative anterior 10% of the stroma (32,380 +/-
      5,848 cells/mm3) that was partially or completely removed during photoablation
      was not reconstituted at 36 months in the anterior 10% of the post-PRK stroma
      (17,720 +/- 4,308 cells/mm3, P < .001). Subbasal nerve fiber bundle density was
      decreased 60% at 12 months after PRK (P < .001) before returning to densities at
      24 and 36 months after PRK that were not significantly different from
      preoperative values (P = 1.0). Activated keratocytes and corneal haze peaked at 3
      months after PRK. CONCLUSIONS: Wounding of the cornea by PRK alters the normal
      structure, cellularity, and innervation of the cornea for up to 36 months.

PMID- 14971585
TI  - The risk of a new retinal break or detachment following cataract surgery in eyes
      that had undergone repair of phakic break or detachment: a hypothesis of a causal
      relationship to cataract surgery.
AB  - PURPOSE: To determine the risk of new retinal tear or detachment following
      cataract surgery in eyes that had undergone successful repair of phakic retinal
      tear or detachment. METHODS: A computerized search of records of patients
      evaluated at the Barnes Retina Institute from 1990 to 2000 for a diagnosis of
      phakic retinal tear or detachment was accomplished. The records of successfully
      treated patients were analyzed by type of tear or detachment, method of
      treatment, and development of sequential new tears or detachment. Eyes that
      subsequently underwent cataract surgery were classified by presence and location
      of intraocular lens as well as operative complications, including capsular
      rupture, vitreous loss, or retained lens fragments. The frequency of developing
      new tears or detachment was calculated. RESULTS: The 2,175 eyes identified were
      subdivided according to those that had undergone repair of retinal break (n =
      1,415), subclinical retinal detachment (n = 396), or retinal detachment (n =
      364). Of 371 eyes that underwent subsequent cataract surgery, 17 (4.6%) developed
      a new tear or detachment postoperatively. Factors indicative of higher
      postoperative risks included myopia, tear or detachment in the fellow eye,
      sequential onset of new breaks prior to cataract surgery, and complications of
      cataract surgery. CONCLUSION: In patients who had undergone prior repair of
      retinal breaks or detachment, cataract surgery was associated with a 4.6%
      incidence of new breaks or detachment. Cataract surgery appears to be an
      independent risk factor for retinal tears or detachments. Dilated retinal
      examination following cataract surgery is advisable in patients who have
      previously undergone repair of a phakic retinal tear or detachment.

PMID- 14971586
TI  - Excimer laser phototherapeutic keratectomy in eyes with anterior corneal
      dystrophies: preoperative and postoperative ultrasound biomicroscopic examination
      and short-term clinical outcomes with and without an antihyperopia treatment.
AB  - PURPOSE: To evaluate the use of high-frequency ultrasound biomicroscopy (UBM) in
      determining the depth of corneal pathology in eyes undergoing excimer laser
      phototherapeutic keratectomy (PTK) for primary or recurrent anterior stromal
      corneal dystrophies. Corneal clarity, visual acuity and refractive changes in
      eyes with and without an antihyperopia treatment were also analyzed. METHODS:
      Twenty eyes of 14 patients with anterior stromal corneal dystrophies were treated
      with PTK. Eyes were evaluated preoperatively and 6 to 8 weeks postoperatively
      with slit-lamp biomicroscopy, manifest refraction, keratometry, computerized
      corneal topography, ultrasound pachymetry, and UBM. RESULTS: Nineteen of 20
      corneas (95%) had greatly improved corneal clarity after PTK. Mean uncorrected
      Snellen vision improved from 20/102 to 20/69 and best corrected vision improved
      from 20/62 to 20/38. Nine eyes (45%) improved 2 or more lines of uncorrected
      vision, and 13 eyes (65%) improved 2 or more lines of best corrected vision. Mean
      change in spherical equivalent was just -0.92 diopters (D); however, the range
      was large (-13 to +3.88 D). UBM measurement of central corneal pathology did not
      correlate with the actual PTK ablation depth (P = .07). The amount of
      antihyperopia treatment did not correlate with changes in manifest refraction
      spherical equivalent, keratometry, or computerized corneal topography readings,
      but did correlate with length of time until corneal reepithelialization after PTK
      (P = .003). CONCLUSIONS: PTK resulted in improvements in corneal clarity and
      visual acuity in most patients with superficial corneal stromal dystrophies. UBM
      was not an effective tool to accurately measure the depth of corneal pathology
      preoperatively. The combined approach of minimizing ablation depth and selective
      use of an antihyperopia treatment resulted in minimal mean change in spherical
      equivalent; however, the range was large. PTK is a very good minimally invasive
      technique to improve vision in eyes with anterior stromal corneal dystrophies.

PMID- 14971587
TI  - Functional magnetic resonance imaging (fMRI) and effects of L-dopa on visual
      function in normal and amblyopic subjects.
AB  - PURPOSE: To evaluate the effects of a single dose of levodopa on visual cortex,
      based on functional MRI (fMRI), and on visual function, based on psychophysical
      tests, in amblyopic and normal subjects. METHOD: A prospective, randomized trial
      of a single dose of levodopa (2 mg/kg body weight) was undertaken in an
      institutional setting in nine normal and six amblyopic subjects, who were
      assessed at baseline and 90 minutes after levodopa ingestion. fMRI of occipital
      visual cortex was undertaken with a 1.5T GE MRI scanner utilizing the BOLD
      contrast technique. fMRI stimuli were two gratings (0.5, 2.0 cycles/degree of
      visual angle) that counterphased at 4 Hz. fMRI parameters for analysis included
      AREA and LEVEL of activation and a SUMMED score (AREA x LEVEL). Psychophysical
      tests included visual acuity, contrast sensitivity, stereoacuity, and binocular
      fusion. RESULTS: At baseline, AREA of activation (P = .05) and SUMMED score (P =
      .05) were significantly less in the amblyopic compared to the dominant eyes.
      Psychophysically, visual acuity and contrast sensitivity were significantly worse
      in the amblyopic eye. Following levodopa ingestion, there was significant
      decrease in LEVEL of activation in the amblyopic eye, even though visual acuity
      showed significant improvement (P = .03). Also, amblyopes showed a significant
      increase and normals showed some decrease in interocular difference in LEVEL of
      activation (P = .04). CONCLUSION: Unique information was obtained when fMRI was
      utilized to assess visual cortical function. While levodopa improved visual
      acuity in the amblyopic eye, it decreased the LEVEL of activation based on fMRI,
      a counterintuitive finding. The results highlight the value of utilizing fMRI to
      assess amblyopia and provide new directions for research.

PMID- 14971588
TI  - Light-adjustable lens.
AB  - PURPOSE: First, to determine whether a silicone light-adjustable intraocular lens
      (IOL) can be fabricated and adjusted precisely with a light delivery device
      (LDD). Second, to determine the biocompatibility of an adjustable IOL and whether
      the lens can be adjusted precisely in vivo. METHODS: After fabrication of a light
      adjustable silicone formulation, IOLs were made and tested in vitro for
      cytotoxicity, leaching, precision of adjustment, optical quality after
      adjustment, and mechanical properties. Light-adjustable IOLs were then tested in
      vivo for biocompatibility and precision of adjustment in a rabbit model. In
      collaboration with Zeiss-Meditec, a digital LDD was developed and tested to
      correct for higher-order aberrations in light-adjustable IOLs. RESULTS: The
      results establish that a biocompatible silicone IOL can be fabricated and
      adjusted using safe levels of light. There was no evidence of cytotoxicity or
      leaching. Testing of mechanical properties revealed no significant differences
      from commercial controls. Implantation of light-adjustable lenses in rabbits
      demonstrated- excellent biocompatibility after 6 months, comparable to a
      commercially available IOL. In vivo spherical (hyperopic and myopic) adjustment
      in rabbits was achieved using an analog light delivery system. The digital light
      delivery system was tested and achieved correction of higher-order aberrations.
      CONCLUSION: A silicone light-adjustable IOL and LDD have been developed to enable
      postoperative, noninvasive adjustment of lens power. The ability to correct
      higher-order aberrations in these materials has broad potential applicability for
      optimization of vision in patients undergoing cataract and refractive surgery.

PMID- 14971589
TI  - Finding and interpreting genetic variations that are important to
      ophthalmologists.
AB  - PURPOSE: To explore two approaches for making the human genome more accessible
      and useful to practicing ophthalmologists. METHODS: DNA samples were obtained
      from patients with inherited eye diseases, and these samples were screened for
      sequence variations in known disease genes with a combination of single-strand
      conformational polymorphism analysis and automated DNA sequencing. Data from this
      screening were then used to evaluate strategies for productively narrowing the
      sample space as well as for estimating the pathogenic potential of variations
      that were discovered in individual patients. For the latter purpose, a universal
      nomenclature for pathogenic potential was proposed based upon the segregation of
      disease alleles and the evolutionary conservation of specific residues as
      reflected by a substitution matrix known as blosum 62. RESULTS: Sequence
      variations were found to be unevenly distributed among disease-associated genes,
      such that screening strategies could be refined to discover more than 50% of
      clinically important sequence variations with only 10% of the effort. The use of
      the blosum 62 matrix was more statistically powerful than our previous method of
      estimating pathogenic probability. CONCLUSIONS: The size of the human genome
      requires that clinical questions be very carefully focused if they are to be
      meaningfully answered in a reasonable amount of time and with a reasonable amount
      of resources. By examining the behavior of known disease genes, one can design
      strategies for significantly focusing the sample space and for more effectively
      interpreting the variations that are found.

PMID- 14971590
TI  - The role of patient age and intraocular gases in cataract progression following
      vitrectomy for macular holes and epiretinal membranes.
AB  - PURPOSE: To evaluate the rate of increase in nuclear sclerosis and posterior
      subcapsular cataracts in eyes as a function of patient age and use of
      intravitreal gas at the time of vitrectomy. METHODS: Nuclear sclerotic cataracts
      and posterior subcapsular cataracts were graded on a scale of 0 to 4.0 in 301
      consecutive eyes prior and subsequent to vitrectomy for macular holes, epiretinal
      membranes, or vitreomacular traction syndrome. Linear regression analysis was
      performed to compare the rate of change in cataract score. RESULTS: Nuclear
      sclerotic cataracts showed minimal increase in patients younger than 50 years of
      age following vitrectomy (.13 grades per year). Nuclear sclerotic cataracts
      increased at a rate of .7 to .9 grades per year (mean, .812) in patients from age
      50 to 60, 60 to 70, 70 to 80, and 80+ years, even though the baseline nuclear
      sclerosis scores were progressively greater for each decade. The increase in
      nuclear sclerotic cataracts in patients younger than 50 years was significantly
      less (P<.001) than in patients 50 years or older. The fellow nonsurgical eyes of
      patients 50 years or older also showed smaller increases in nuclear sclerotic
      cataracts over time (.091 to .342 grades per year; mean, .139). Eyes with
      intraocular gas use had a higher rate of nuclear sclerosis progression (.8 grades
      per year) compared to eyes without intraocular gas bubbles (.5 grades per year)
      (P<.001). Posterior subcapsular cataract scores showed minimal or no increases in
      all groups. CONCLUSIONS: Patients older than 50 years have a similar rate of
      increase in nuclear sclerotic cataracts independent of age. The rate is sixfold
      greater than in patients younger than 50 years and also sixfold greater than the
      progression of nuclear sclerosis in the fellow nonsurgical eyes. Intravitreal gas
      bubbles cause nuclear sclerosis to increase by 60%, compared to eyes without use
      of a gas bubble.

PMID- 14971592
TI  - Leishmania tropica (Kinetoplastida: Trypanosomatidae)--a perplexing parasite.
AB  - Leishmania tropica is one of the causative agents of cutaneous leishmaniasis
      (CL), a disfiguring parasitic disease that recently was found to be
      viscerotropic. In urban areas it is transmitted from infected individuals by the
      bite of phlebotomine sand flies to naive persons (anthroponotic CL). In rural
      areas animals are thought to be the reservoir, but the full life cycle is still
      under investigation (zoonotic CL). For many years L. tropica was either confused
      or merely grouped with L. major while Phlebotomus sergenti was the only proven
      vector. In recent years new foci have erupted, but few have been investigated.
      This review describes some of the history, recent findings, epidemiology,
      potential vectors, and the search for possible reservoir hosts besides man.

PMID- 14971593
TI  - Myxobolus buckei sp. n. (Myxozoa), a new pathogenic parasite from the spinal
      column of three cyprinid fishes from the United Kingdom.
AB  - Myxobolus buckei sp. n. is described from the spinal column of Leuciscus cephalus
      (L.), Rutilus rutilus (L.) and Abramis brama (L.) from freshwater rivers in the
      North of England. The plasmodia develop within the remnants of the embryonic
      notochord in the intervertebral spaces. The spores are large, measuring (in
      microm) 14.0 +/- 0.7 x 11.5 +/- 0.6 (mean +/- SD), smooth, round to ellipsoid in
      valvular view with several sutural edge markings. The polar capsules are pyriform
      and of equal size, measuring 7.5 +/- 0.5 x 4.2 +/- 0.2 (mean +/- SD), with 11-12
      turns of the polar filament arranged perpendicularly to the longitudinal axis of
      the polar capsule. The parasite has a large intercapsular appendix and large
      iodinophorous vacuole. The parasite can be differentiated from all known species
      of Myxobolus Butschli, 1882 by a combination of the morphological characters
      defined. Infected fish show marked longitudinal compression of the body compared
      to uninfected individuals of the same year class, a feature which is
      pathognomonic for the disease. Histologically, host responses ranged from mild
      hypertrophy of the zygapophyseal process and expansion of the intervertebral
      membrane to complete hypertrophy and fusion of the vertebrae. Prominent notochord
      is present in the intervertebral spaces of infected fish and sporogony of the
      parasite leads to a vigorous focal inflammatory response involving proliferating
      fibroblast and osteogenic cells. The parasite causes a radial expansion of the
      centra and extensive dorsal and ventral outgrowths of the vertebrae leading to
      compression of the spinal cord and blood vessels running through the neural and
      haemal spines respectively. The parasite is considered highly pathogenic to
      juvenile cyprinids.

PMID- 14971595
TI  - Ellipsomyxa gobii gen. et sp. n. (Myxozoa: Ceratomyxidae) in the common goby
      Pomatoschistus microps (Teleostei: Gobiidae) from Denmark.
AB  - A new myxosporean species Ellipsomyxa gobii gen. et sp. n. is described from the
      common goby Pomatoschistus microps (Kroyer) (Perciformes, Gobiidae). Plasmodia
      with long branched pseudopodia in the gallbladder develop to subspherical
      bisporous plasmodia. The myxospores were found in the gallbladder, and the
      hepatic and bile ducts. The new genus is characterised by the morphology of the
      myxospores. The myxospores have smooth thin valves elongated in the direction
      perpendicular to the plane of the straight central transverse indistinct sutural
      line. The two spherical polar capsules open some distance from the sutural line
      on opposite sides. The new genus thereby differs from Leptotheca Thelohan, 1895.
      Ellipsomyxa gobii is tentatively placed in the Ceratomyxidae.

PMID- 14971594
TI  - New data on Myxobolus longisporus (Myxozoa: Myxobolidae), a gill infecting
      parasite of carp, Cyprinus carpio haematopterus, from Chinese lakes.
AB  - The original description of Myxobolus longisporus Nie et Li, 1992, the species
      infecting gills of Cyprinus carpio haematopterus L., is supplemented with new
      data on the spore morphology and pathogenicity. Spores are elongate pyriform with
      pointed anterior end, 15.7 (15.5-16.5) microm long, 6.7 (6-8) microm wide and 5.5
      microm thick. Sutural ridge is straight and narrow. Mucus envelope is lacking.
      Two equal-sized elongate pyriform polar capsules are 8.5 microm long and 2.5
      microm wide with convergent long axes. Polar filament coiled perpendicularly to
      the long axis of the capsule makes 9 (8-10) turns. Posterior end of polar
      capsules exceeds mid-spore by 15-20%. Cyst-like plasmodia are localised in the
      gill secondary lamellae. The infection is described in adult big host specimens.
      Gross lesions manifested as dark red colouration of gill tissues were restricted
      to the ventral part of the first gill arches. Remarkable site specificity (apical
      part of secondary lamellae) was observed in the course of development of
      microscopic lesions. M. longisporus is characterised also on the molecular level
      using sequences of SSU rRNA gene. Phylogenetic analysis based on these sequences
      has allowed clearer phylogenetic relationships to be established with other
      species of the genus Myxobolus sequenced to date.

PMID- 14971591
TI  - Analysis of retinal pigment epithelium integrin expression and adhesion to aged
      submacular human Bruch's membrane.
AB  - PURPOSE: Uncultured aged retinal pigment epithelium (RPE) does not resurface aged
      Bruch's membrane after 24 hours in organ culture. These experiments assess
      whether culturing alters RPE integrin expression and resurfacing of Bruch's
      membrane. METHODS: RNA was isolated from uncultured and cultured RPE of aged
      adult donor and fetal eyes. Integrin subunit messenger RNA (mRNA) expression was
      studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and
      semiquantitative analysis of the amplified products. Cell surface integrin
      expression was assessed using flow cytometry. Passaged cultured fetal RPE and
      primary cultured aged RPE were seeded onto Bruch's membrane, and resurfacing was
      assessed with scanning electron microscopy. RESULTS: Uncultured fetal RPE had low
      levels of alpha3 and beta5 mRNA compared to passaged cultured fetal RPE.
      Uncultured aged RPE had decreased alpha1-5 mRNA compared to primary cultured aged
      RPE. Cultured aged RPE had decreased beta4 and beta5 mRNA compared to passaged
      cultured fetal RPE. Flow cytometry confirmed the expression of alpha1-5, alphav,
      and beta1 protein on cultured fetal RPE and alpha1-3 and beta1 protein on
      cultured aged RPE. Twenty-four hours after seeding, cultured fetal and aged RPE
      resurfaced 99% +/- 1.3% and 76% +/- 22%, respectively, of aged submacular Bruch's
      membrane specimens from which native RPE had been debrided, exposing the native
      RPE basement membrane. Cultured fetal and aged RPE resurfaced 97% +/- 3.1% and
      39% +/- 35%, respectively, of specimens in which the inner collagenous layer was
      exposed. CONCLUSIONS: Uncultured aged RPE has low amounts of integrin subunits
      that form receptors for laminin, fibronectin, and collagens. Culturing up
      regulates integrins and promotes more efficient aged RPE attachment to and
      survival on aged Bruch's membrane.

PMID- 14971596
TI  - Annulotrematoides bryconi sp. n. (Monogenea: Dactylogyridae) parasitic on Brycon
      cephalus (Osteichthyes: Characidae) from Brazil.
AB  - Annulotrematoides bryconi sp. n. is described and illustrated from specimens
      collected from gills of characiform fish, Brycon cephalus (Gunther, 1869), in
      pisciculture ponds from Pirassununga, Sao Paulo, Brazil. Diagnostic characters of
      the new species are the tegument of trunk showing annulations, except on the
      cephalic regiona, and copulatory complex comprising sclerotized male copulatory
      organ coiled in 1 1/2 rings. This is the first record of monogeneans parasitic on
      the gills of B. cephalus.

PMID- 14971597
TI  - Ultrastructure of Archigetes sieboldi (Cestoda: Caryophyllidea): relationship
      between progenesis, development and evolution.
AB  - Ultrastructural characteristics of progenetic and monoxenic Archigetes sieboldi
      Leuckart, 1878 from the oligochaete Limnodrilus hoffmeisteri Claparede are
      described. Our observations demonstrate that progenetic Archigetes sieboldi
      shares characteristics of both larval (progenetic) and adult stages. The primary
      larval characteristics are: the presence of a cercomer; a surface filamentous
      coat covering the whole worm; the presence of the penetration glands and the
      absence of tegumental ones; wide sarcoplasmic processes connecting the circular
      and longitudinal external tegumental muscles; the absence of the dense homogenous
      zone of the basal lamina beneath the epithelial cytoplasm of all reproductive
      organs and ducts; non-functional gonopores; and an orthogonal plan of nervous
      system with three pairs of longitudinal nerve trunks. The principle adult
      characteristics are: oogenesis, spermiogenesis and vitellogenesis that produce
      fertilized eggs; the uterine glands; a well-developed longitudinal tegumental
      muscle layer between tegumental cytons; and the presence of different
      microtriches. As a result of this progenetic development there has been a
      secondary reduction in the life cycle of A. sieboldi. It is postulated that a
      similar process of progenesis may have played a major role in the early evolution
      of the Caryophyllidea by first appearing in a plerocercoid stage of an ancestral
      strobilate cestode from fish.

PMID- 14971598
TI  - Neoechinorhynchus (Neoechinorhynchus) zabensis sp. n. (Acanthocephala:
      Neoechinorhynchidae) from freshwater fish in northern Iraq.
AB  - Neoechinorhynchus (Neoechinorhynchus) zabensis sp. n. (Acanthocephala:
      Neoechinorhynchidae) is described from Capoeta damascina (Valenciennes, 1842)
      (type host) and Capoeta trutta (Heckel, 1843) in the Greater and Lesser Zab
      Rivers, northern Iraq. The new species is unique among all other species of the
      genus by its characteristic paired para-vaginal muscular appendage and fragmented
      giant nuclei in the lemnisci. Eleven of the other 88 valid species of
      Neoechinorhynchus and N. zabensis have middle and posterior hooks of equal
      length. However, N. zabensis is distinguished from the others by size of trunk,
      proboscis, proboscis hooks and lemnisci, number of giant nuclei, position of
      female gonopore, and geographical and host distribution. It is also distinguished
      from six other species of Neoechinorhynchus previously reported from Iraq. Other
      distinguishing features are also included.

PMID- 14971599
TI  - Observations on the metazoan parasites of the Atlantic salmon (Salmo salar) after
      its reintroduction into the Elbe River basin in the Czech Republic.
AB  - In the years 1999-2002, first studies were carried out on the metazoan parasites
      of Atlantic salmon (Salmo salar L.) recently reintroduced into the Elbe River
      drainage system, after more than 50 years after the complete extinction of the
      Elbe salmon population. A total of six helminth species were recorded from salmon
      smolts from three streams of the Elbe River basin (Kamenice River, Jestedsky and
      Libocansky Brooks) in North Bohemia, Czech Republic, where S. salar fingerlings
      have been released since 1998: Gyrodactylus truttae Glaser, 1974, Crepidostomum
      metoecus Braun, 1900, Diplostomum spathaceum (Rudolphi, 1819) metacercariae,
      Raphidascaris acus (Bloch, 1799) adults and encapsulated larvae, Cystidicoloides
      ephemeridarum (Linstow, 1872), and Neoechinorhynchus rutili (Muller, 1780).
      Except for D. spathaceum, all these freshwater parasites have been received from
      the helminth fauna of the co-habiting brown trout (Salmo trutta fario L.). Due to
      local ecological conditions, the parasite faunae of both salmon and brown trout
      exhibited distinct qualitative and quantitative differences in the three
      localities. The finding of G. truttae on S. salar represents a new host record.
      Three helminth parasites of marine origin, the cestodes Eubothrium crassum
      (Bloch, 1779) and Scolex pleuronectis Muller, 1788 plerocercoids, and the
      nematode Anisakis simplex (Rudolphi, 1809) larvae were found in the single
      examined adult S. salar from the Kamenice River. New data on the geographical
      distribution of some nematode parasites of Salmo trutta fario L., Barbatula
      barbatula (L.) and Anguilla anguilla (L.) are presented.

PMID- 14971600
TI  - Modulation of human lymphocyte proliferation by salivary gland extracts of ixodid
      ticks (Acari: Ixodidae): effect of feeding stage and sex.
AB  - Ixodid ticks remain attached to their hosts for several days to weeks. During
      this extended feeding process new proteins involved in the modulation of host
      immune responses are expressed in tick salivary glands. In our study a
      stimulatory or inhibitory effect of salivary gland extracts (SGE) of unfed and
      partially fed female Ixodes ricinus (Linnaeus, 1758), female and male Amblyomma
      variegatum (Fabricius, 1794) and Rhipicephalus appendiculatus Neumann, 1901 ticks
      on human lymphocyte proliferation induced by Concanavalin A (ConA) and
      phytohaemagglutinin (PHA), respectively, was investigated. SGE of all female
      ticks examined suppressed proliferation of ConA-induced lymphocytes; highly
      significant suppression was observed in the presence of unfed I. ricinus and 9
      day fed A. variegatum SGE. SGE of partially fed A. variegatum and I. ricinus
      females suppressed PHA responses of lymphocytes. Lymphocytes showed reduced PHA
      and ConA responses in the presence of SGE of unfed and 2-day fed R.
      appendiculatus females, while SGE of 6-day fed females enhanced PHA responses,
      but reduced their ConA responses; generally SGE of 2-day fed females displayed
      the strongest inhibition. Amblyomma variegatum male SGE slightly enhanced PHA,
      but significantly reduced ConA responses of lymphocytes and their inhibitory
      effect increased during feeding. SGE of unfed and 2-day fed R. appendiculatus
      males enhanced PHA and ConA responses and those of 6-day fed males suppressed
      lymphocyte proliferation. The results suggest that (i) species- and sex-specific
      differences exist in the effects of tick salivary gland antigens on human
      lymphocyte proliferation and (ii) effect of SGE on human lymphocyte responses to
      mitogens varies depending on the tick feeding status.

PMID- 14971601
TI  - Ephemera strigata imagoes are the likely source of a parasitic nematode infection
      of fish.

PMID- 14971602
TI  - Path coefficient analysis of correlation between breeding cycles of the common
      myna Acridotheres tristis (Passeriformes: Sturnidae) and its phthirapteran
      ectoparasites.

PMID- 14971603
TI  - Scoring analysis of salivary gland scintigraphy in patients with Sjogren's
      syndrome.
AB  - The purpose of the present study was to evaluate the validity of a scoring system
      based on excretion rate of salivary gland scintigraphy in patients with Sjogren's
      syndrome (SjS). Total scintigraphic scores were compared with the results of the
      Saxon test. One hundred and twenty-four subjects who were clinically diagnosed
      with SjS and 11 normal ones underwent salivary gland scintigraphy and the Saxon
      test. In salivary gland scintigraphy, the difference between maximum and minimum
      counts after stimulation using vitamin C divided by maximum counts was defined as
      the excretion rate. We then defined a scoring system with 4 grades: severe
      dysfunction = 3 (excretion rate < 25%), moderate dysfunction = 2 (25% < or =
      excretion rate < 40%), mild dysfunction = 1 (40% < or = excretion rate < 50%) and
      normal function = 0 (50% < or = excretion rate). The summation of the total
      scintigraphic score (0-12) of all 4 salivary glands was used as a semi
      quantitative index indicating total salivary gland function, and total
      scintigraphic scores were compared with the results of the Saxon test. A
      significant inverse linear correlation (R2 = 0.95) was observed between total
      scintigraphic scores and mean values of the Saxon test within a range of abnormal
      scintigraphic scores (> or = 4). The scoring system developed in the present
      study is a clinically available, objective, and reproducible method for
      evaluation of salivary gland function in patients with SjS.

PMID- 14971604
TI  - Clinical usefulness of iodine-123-MIBG scintigraphy for patients with
      neuroblastoma detected by a mass screening survey.
AB  - The purpose of this study was to evaluate the usefulness in a clinical setting of
      iodine-123-metaiodobenzylguanidine (123I-MIBG) scintigraphy, planar and single
      photon emission computed tomography (SPECT) images, in patients with
      neuroblastoma as detected by a mass screening survey. METHODS: 123I-MIBG planar
      whole body images, and regional SPECT images of patients with neuroblastoma in 51
      studies were reviewed. They were all detected by a mass screening survey
      performed in the 6th month after birth using vanil mandelic acid (VMA), and
      homovanillic acid (HVA) and the neuroblastoma had been confirmed by surgery.
      Scintigraphy was performed 24 hours after injection of 111 MBq of 123I-MIBG. We
      assessed the accuracy of the planar whole body images in order to demonstrate the
      extent of the lesion and the correlation between the degree and extent of the
      lesions of 123I-MIBG accumulation and clinical staging with tumor markers, such
      as urinary VMA, urinary HVA, serum neuron specific enolase (NSE) and serum
      lactate dehydrogenase (LDH). Additionally, we evaluated SPECT how useful
      supplemental SPECT might be in a clinical setting as compared with planar whole
      body images. RESULTS: 123I-MIBG planar whole body images revealed all 33 (100%)
      primary lesions, 4 of the 5 cases (80%) with liver metastasis, 3 of the 13 (23%)
      with lymph nodes metastasis and 1 of 3 (33%) with bone marrow infiltration. The
      extent and degree of accumulation correlated with the values of urinary VMA,
      urinary HVA and serum NSE. SPECT images helped to understand the positional
      relation in all cases and provided useful additional information for clinical
      staging in 7 cases. CONCLUSION: 123I-MIBG scintigraphy with planar and SPECT
      images is useful for evaluating patients with neuroblastoma, following detection
      by a mass screening survey.

PMID- 14971605
TI  - Three-dimensional stereotactic surface projection of brain perfusion SPECT
      improves diagnosis of Alzheimer's disease.
AB  - OBJECTIVES: Alzheimer's disease (AD) is diagnosed by either inspection of the
      brain perfusion SPECT, or three-dimensional stereotactic surface display (3D
      SSP). The purpose was to compare diagnostic performances of these methods.
      METHODS: Sixteen nuclear medicine physicians independently interpreted 99mTc-ECD
      SPECT in one session and SPECT with 3D-SSP in another session without clinical
      information for 50 studies of AD patients and 40 studies of healthy volunteers.
      Probabilities of AD were reported according to a subjective scale from 0%
      (normal) to 100% (definite AD). Receiver operating characteristics curves were
      generated to calculate areas under the ROC curves (Az's) for the inspection as
      well as for an automated diagnosis based on a mean Z value in the bilateral
      posterior cingulate gyri in a 3D-SSP template. RESULTS: Mean Az for visual
      interpretation of SPECT alone (0.679 +/- 0.058) was significantly smaller than
      that for visual interpretation of both SPECT and 3D-SSP (0.778 +/- 0.060). Az for
      the automated diagnosis (0.883 +/- 0.037) was significantly greater than that for
      both modes of visual interpretation. CONCLUSIONS: 3D-SSP enhanced performance of
      the nuclear medicine physicians inspecting SPECT. Performance of the automated
      diagnosis exceeded that of the physicians inspecting SPECT with and without 3D
      SSP.

PMID- 14971606
TI  - Medical economics of whole-body FDG PET in patients suspected of having non-small
      cell lung carcinoma--reassessment based on the revised Japanese national
      insurance reimbursement system.
AB  - Focusing on the savings expected from the revised Japanese national insurance
      reimbursement system in the management of patients suspected of having non-small
      cell lung carcinoma (NSCLC), cost-effectiveness was assessed using decision tree
      sensitivity analysis on the basis of the 2 competing strategies of whole-body FDG
      PET (WB-PET) and conventional imaging (CI). METHODS: A WB-PET strategy that
      models dependence upon chest FDG PET scan, WB-PET scan, and brain MR imaging with
      contrast was designed. The cost of a FDG PET examination was updated and
      determined to be US dollar 625.00. The CI strategy involves a combination of
      conventional examinations, such as abdominal CT with contrast, brain MR imaging
      with contrast, and a whole-body bone scan. A simulation of 1,000 patients
      suspected of having NSCLC (Stages I to IV) was created for each strategy using a
      decision tree and baselines of other relevant variables cited from published
      data. RESULTS: By using the WB-PET strategy in place of the CI strategy for the
      management of patients suspected of having NSCLC in hospitals with an NSCLC
      prevalence of 75%, the cost saving (CS) for each patient would be US dollar
      697.69 for an M1 prevalence of 20% and US dollar 683.52 for an M1 prevalence of
      40%, but the CS gradually decreases as the NSCLC prevalence increases. The break
      even point requires less than an 80% prevalence in order for the WB-PET strategy
      to gain life expectancy (LE) per patient. By using the WB-PET strategy in place
      of the CI strategy for the management of patients suspected of having NSCLC in
      hospitals with an NSCLC prevalence of 75%, the gain in LE for each patient would
      be 0.04 years (11.06 vs. 11.02 years) for an M1 prevalence of 20% and 0.10 years
      (10.13 vs. 10.03 years) for an M1 prevalence of 40%. The maximum cost of a PET
      study without losing LE would be US dollar 1322.68 per patient for prevalences of
      75% NSCLC and 20% M1 disease. CONCLUSIONS: The present study quantitatively
      showed WB-PET, employed in place of CI for managing NSCLC patients, to be cost
      effective in the Japanese revised insurance reimbursement system. However, the
      present cost is very low from the industrial viewpoint.

PMID- 14971607
TI  - Usefulness of 67Ga scintigraphy in extranodal malignant lymphoma patients.
AB  - OBJECTIVE: 67Ga scintigraphy has a well-documented role in nodal lymphoma for
      both disease staging and assessment of treatment response. The objective of the
      present study was to examine the role of 67Ga scintigraphy in diagnosis and
      assessment of treatment response, in patients with extranodal malignant lymphoma.
      METHODS: Seventy-one patients with extranodal malignant lymphoma were studied.
      Whole body scans in all and SPECT scans in some selected patients were performed
      72 hours after injection of 67Ga-citrate. The influence of tumor site,
      histological classification and tumor size on 67Ga scintigraphy sensitivity was
      analyzed. Twenty-one of the seventy-one patients also had a second 67Ga
      scintigraphy to assess response to treatment. RESULTS: The overall 67Ga
      scintigraphy sensitivity was 83.1% (59/71). The sensitivity was low in patients
      whose extranodal lymphoma occurred in skin (0/3) and urinary bladder (0/1), as
      compared to other tumor sites. According to the histological classification of
      the lesion, the sensitivity was lower in low-grade than in intermediate and high
      grade lymphoma. According to the tumor size, the sensitivity was low in lesions
      less than 2 cm in diameter than those more than 2 cm in diameter. The results
      changed from positive to negative accumulation in 20 (95.2%) of the 21 patients
      who had 67Ga scintigraphy to assess the response to treatment. These 20 patients
      showed a good clinical course. CONCLUSIONS: Although 67Ga scintigraphy did not
      show positive accumulation in patients with skin and urinary bladder lymphoma, it
      was helpful to confirm the diagnosis and to evaluate the therapeutic effect in
      most patients with extranodal malignant lymphoma.

PMID- 14971608
TI  - Differential renal function in the prediction of recovery in adult obstructed
      kidneys after pyeloplasty.
AB  - AIM: Pyeloplasty is a widely accepted method for the treatment of ureteropelvic
      junction obstruction (UPJO). Surgery has long been thought to affect
      postoperative renal function. However, controversies still exist on the
      functional studies that can be used to indicate which renal units will benefit
      from surgery. In this study, the correlation between differential renal function
      (DRF) and other preoperative parameters was examined to determine which parameter
      more accurately predicts recovery of renal function in adult obstructed kidneys.
      MATERIALS & METHODS: In this study, the authors evaluated 32 patients with UPJO.
      In all patients, standart diuretic Tc-99m DTPA renal scans were performed
      preoperatively and 6 months after surgery. Patients were divided into two groups
      according to the preoperative DRF (> or = 30%, n = 22, group I and < 30%, n = 10,
      group II). Second type classification was made according to the postoperative DRF
      improvement as improved (group A, n = 13) and not improved (group B, n = 19).
      These groups were then compared regard to variables which were defined as
      symptoms, age at operation and ultrasonographic findings. We also evalulated
      whether preoperative parenchymal function is important to predict improvement in
      drainage half-time (T1/2). RESULTS: While preoperative drainage half-time was
      39.6 +/- 15.9 minutes, postoperative half-time decreased to 16.9 +/- 6.8 minutes
      (p < 0.001). The mean DRF did not improved significantly after surgery compared
      with preoperative values (32.03 +/- 9.42% versus 36.16 +/- 9.60%). When comparing
      the patients with preoperative DRF > or = 30% (group I, DRF 38 +/- 0.8%) to those
      who had an initial DRF below 30% (group II, DRF 22.8 +/- 5.2%), postoperative DRF
      was 41.22 +/- 5.72 in group I and 25.00 +/- 6.22 in group II. The difference was
      significant (p < 0.01). The patients in group I and II showed improvement in 50%
      and 20%, respectively. Age, clinical presentation and ultrasonographic findings
      did not affect functional outcome after pyeloplasty. We could not find any
      correlation between preoperative DRF and the degree of improvement in T1/2.
      CONCLUSION: Renal function improves after pyeloplasty with regard to the initial
      level of split renal function in adult obstructed kidneys. Improvement may not be
      observed especially in patients with DRF less than 30%.

PMID- 14971609
TI  - Utility of 99mTc dextran scintigraphy in diabetic patients with suspected
      osteomyelitis of the foot.
AB  - PURPOSE: Osteomyelitis of the foot is a frequent complication of diabetes
      mellitus and its diagnosis is often difficult. The goal of this study was to
      demonstrate the utility of 99mTc dextran scintigraphy in suspected diabetic foot
      infections. MATERIALS AND METHODS: Twenty-six patients (20 males, 6 females, age
      range 18-80 years) with diabetes mellitus who had a total of 36 foot ulcers or
      necrosis were studied. All the patients underwent both three phase bone scan and
      99mTc dextran scintigraphy. Final diagnosis was based upon either pathologic
      examination or clinical follow-up at least four months. RESULTS: On bone scan
      increased uptake was seen in 55 sites, and among these there were 11 lesions of
      proven osteomyelitis. There were 11 true-positive, 0 false negative, 0 true
      negative and 44 false positive results for bone scan. The sensitivity,
      specificity and accuracy of bone scan were 100%, 0% and 20%, respectively. With
      regard to 99mTc dextran scan, nine lesions produced true-positive results with
      two lesions indicating false negatives resulting in a sensitivity of 82%. Thirty
      six true negative and eight false positive results produced a specificity of 82%,
      and an accuracy 82% from 99mTc dextran studies was obtained. Eight false-positive
      results were possibly due to neuroarthropathy, pressure points and deep
      penetrating ulcers. A patient with one false-negative result had angiopathy while
      other had neither neuropathy nor angiopathy. CONCLUSIONS: According to these
      results, 99mTc dextran scintigraphy seems to be a sensitive and specific
      diagnostic method, and because of its advantages over other radiopharmaceuticals
      (shorter preparation time, highly stability in vivo/in vitro, early diagnostic
      imaging and low cost), it may be a radiopharmaceutical of choice for diagnosing
      in diabetic foot infections.

PMID- 14971610
TI  - The effect of beta-blocker on hamster model BIO 53.58 with dilated cardiomyopathy
      determined using 123I-MIBG myocardial scintigraphy.
AB  - OBJECTIVE: 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is
      currently used to evaluate cardiac sympathetic nerve function, but MIBG also has
      the capacity to evaluate dilated cardiomyopathy (DCM) severity and therapeutic
      effectiveness. In this study, we administered beta-blockers to a DCM hamster
      model and evaluated the effect of therapy using MIBG. We also pathologically
      compared the effects of myocardial fibrosis suppression. METHODS: BIO 53.58
      hamsters were divided into the following five groups based on beta-blocker
      administration: vehicle (COT), 2 mg/kg/day carvedilol (CLT), 20 mg/kg/day (CHT)
      carvedilol, 4 mg/kg/day (MLT) metoprolol, 40 mg/kg/day (MHT) metoprolol. F1B
      hamsters were administered a vehicle (COF). Plasma catecholamine, noradrenaline
      (p-NADR), adrenaline (p-ADR), and dopamine (p-DOPA) were assayed, and MIBG was
      performed. The count ratio of the heart to the mediastinum (H/M) and left
      ventricle myocardial washout ratio (WR) were calculated. We then performed an
      autopsy and calculated the percent change in fibrotic area from myocardial
      sections. RESULTS: H/M of the initial image in the COT group was significantly
      lower at 2.4 +/- 0.2 than the 2.9 +/- 0.7 in the COF group (p < 0.05). The CLT
      and CHT groups had higher H/M values compared to the COT group (3.1 +/- 0.6, 3.0
      +/- 0.6 versus 2.4 +/- 0.2: p < 0.05). Significant correlations were evident
      between the H/M of the delayed image and p-NADR and p-DOPA (p < 0.05, p < 0.01,
      respectively) as well as between WR and p-NADR and p-DOPA (p < 0.05). Percent
      change in fibrotic area was significantly lower in the beta-blocker groups than
      in the COT group (p < 0.05). Significant negative correlations were seen between
      the H/M of the delayed image and the percent change in fibrosis area.
      CONCLUSIONS: The delayed image H/M and WR acutely reflected cardiac disorder and
      sympathetic nerve function disorder in BIO 53.58 hamsters. In the carvedilol
      administered groups, there was improvement compared to the initial H/M image,
      indicating the efficacy of the beta-blocker in DCM.

PMID- 14971611
TI  - Uterine doughnut in early proliferating phase: potential pitfall in
      gastrointestinal bleeding studies.
AB  - A 41-year-old woman with rectal bleeding was referred to our department for
      gastrointestinal (GI) bleeding study. She was in early post-menstrual period and
      had stable vital signs. A GI bleeding study with Tc-99m SC revealed uterine blush
      in the pelvis. The shape of activity and quick fading excluded a GI bleeding. To
      rule out an intermittent bleeding, patient underwent a second bleeding study with
      Tc-99m RBC. Serial images showed uterine "doughnut" in the pelvis. The activity
      neither changed in shape nor showed distal movement with time excluding a GI
      hemorrhage. Uterus in early proliferating phase could be a potential pitfall in
      GI bleeding studies.

PMID- 14971612
TI  - Gallium-67 accumulation to the tumor thrombus in anaplastic thyroid cancer.
AB  - A sixty-five-year-old woman was hospitalized for examination of swelling in the
      left arm. Gallium-67 scintigraphy showed the same radioactivity in the left lobe
      of the thyroid gland and the junction of the internal jugular vein and the
      subclavian vein. Operation then proved obstruction of the left internal jugular
      vein and subclavian vein due to tumor thrombus accompanied by anaplastic thyroid
      cancer. Gallium-67 scintigraphy was extremely useful in grasping the extent and
      feature of the tumor.

PMID- 14971613
TI  - Scintigraphic progress of the liver in a patient with Alagille syndrome
      (arteriohepatic dysplasia).
AB  - We encountered a 9-year-old Japanese girl with Alagille syndrome. Her
      scintigraphic examinations of the liver were performed at the ages of 16 months
      and 9 years. 99mTc-PMT, a hepatobiliary imaging agent, was distributed
      homogeneously in the liver at the younger age, but unevenly produced an area of
      focally increased uptake in the medial segment of the liver surrounded by
      peripheral atrophy at the older age. 99mTc-GSA, a hepatoreceptor binding agent,
      was highly accumulated in the area, corresponding to the focally increased uptake
      of 99mTc-PMT. These imaging findings suggest that the pathophysiological and
      morphological changes of the liver occurred in our patient during the clinical
      course.

PMID- 14971614
TI  - What is the diagnosis? Malignant external otitis (MEO) (Pseudomonas osteomyelitis
      of the temporal bone).

PMID- 14971615
TI  - Case report: unstable angina with flow-fatty acid metabolism mismatch and reverse
      flow-glucose metabolism mismatch patterns.
AB  - A 79-year-old man with unstable angina underwent an emergency coronary
      angiography, and percutaneous balloon angioplasty was performed for LCX. Left
      ventriculography showed hypokinesis in the posterior wall, inferior and apical
      wall immediately after the PCI therapy. The defects on 123I-BMIPP SPECT seen in
      the inferior, posterior and lateral wall were more extensive than those observed
      on 99mTc-MIBI SPECT, and a flow-fatty acid metabolism mismatch pattern was
      observed. The 18F-FDG PET showed reduced uptake in the lateral segment, although
      13N-NH3 PET showed normal perfusion, and a reverse flow-glucose metabolism
      mismatch pattern was observed. Left ventriculography showed significant improve
      to normal contraction on the 3-month follow up, and there was not significantly
      reduced uptake in 99mTc-MIBI SPECT, 123I-BMIPP SPECT, 13N-NH3 PET or 18F-FDG PET.

PMID- 14971616
TI  - Tc-99m HMPAO brain SPECT in linear nevus sebaceous syndrome.
AB  - The authors present a case of linear nevus sebaceous syndrome (LNSS) with atrophy
      of bilateral frontotemporal areas of the brain, left cerebellum and hippocampus,
      and bilateral uncal dysplasia demonstrated by magnetic resonance imaging (MRI).
      Magnetic resonance angiography revealed bilateral internal carotid artery
      hypoplasia with absence of flow in the anterior and middle cerebral arteries. Tc
      99m HMPAO brain SPECT demonstrated more areas of perfusion defects while MRI
      detected volume loss and gliosis in affected areas. Tc-99m HMPAO brain SPECT may
      be more useful for revealing absent or decreased perfusion areas of brain lesions
      than MRI in LNSS.

PMID- 14971617
TI  - Transient increase in wall thickness of the left ventricular apex during recovery
      from "ampulla" cardiomyopathy.
AB  - "Ampulla" cardiomyopathy is a syndrome characterized by transient abnormal left
      ventricular wall motion with hypokinesia around the apical area and hyperkinesia
      at the basal area, without any detectable coronary lesion. Two cases of transient
      wall thickening of the left ventricular apex during recovery from "ampulla"
      cardiomyopathy are described. Apical wall thickening was documented by left
      ventriculography, echocardiography, and thallium (201Tl) single-photon emission
      computed tomography (SPECT) during the recovery phase. The thickness of the
      apical wall subsequently returned to normal. Both patients underwent provocation
      tests. Coronary spasms were positive. This transient increase in left ventricular
      apical volume may have been caused by myocardial inflammation secondary to
      "ampulla" cardiomyopathy.

PMID- 14971618
TI  - Gated blood pool SPECT improves reproducibility of right and left ventricular
      Fourier phase analysis in radionuclide angiography.
AB  - OBJECTIVES: The ventricular phase angle, a parametric method applied to Fourier
      phase analysis (FPA) in radionuclide ventriculography, allows the quantitative
      analysis of ventricular contractile synchrony. However, FPA reproducibility using
      gated blood pool SPECT (GBPS) has not been fully evaluated. The present study
      evaluates whether by using GBPS, the reproducibility of FPA could be improved
      over that in planar radionuclide angiography (PRNA). METHODS: Forty-three
      subjects underwent both GBPS and PRNA, of which 10 subjects were normal controls,
      25 had dilated cardiomyopathy, and 8 had various heart diseases. Interventricular
      contractile synchrony was measured as the absolute difference in RV and LV mean
      ventricular phase angle as delta(phi) (RV - LV). Intraventricular contractile
      synchrony was measured as the standard deviation of the mean phase angle for the
      RV and LV blood pools (RVSD(phi), LVSD(phi)). Two nuclear physicians processed
      the same phase images of GBPS to evaluate the interobserver reproducibility of
      the phase angles using data from the 43 study participants. Phase images acquired
      from PRNA were processed in the same manner. RESULTS: Excellent reproducibility
      of delta(phi) (RV - LV) was obtained with both GBPS (Y = -3.10 + 0.89 x X; r =
      0.901) and PRNA (Y = -4.51 + 0.81 x X; r = 0.834). In regard to RVSD(phi)
      reproducibility was not adequate with PRNA (Y = 18.56 + 0.35 x X; r = 0.424),
      while it was acceptable with GBPS (Y = 5.22 + 0.85 x X; r = 0.864). LVSD(phi)
      reproducibility was superior using both GBPS (Y = 4.15 + 0.97 x X; r = 0.965) and
      PRNA (Y = -0.55 + 0.98 x X; r = 0.910). CONCLUSION: Our results demonstrate FPA
      obtained using GBPS to be highly reproducible for evaluating delta(phi) (RV -
      LV), RVSD(phi) and LVSD(phi), in comparison with the PRNA method. We thus
      consider GBPS appropriate for evaluating ventricular contractile synchrony.

PMID- 14971619
TI  - Estimation with Tc-99m tetrofosmin SPECT of salvaged myocardial mass after
      emergent reperfusion therapy in acute myocardial infarction.
AB  - OBJECTIVES: The purpose of this study was to validate a new quantitative index of
      salvaged myocardial mass calculated from Tc-99m tetrofosmin SPECT for evaluating
      the therapeutic effect of emergent reperfusion therapy in acute myocardial
      infarction (AMI). METHODS: Tc-99m tetrofosmin SPECT was performed before and
      after emergent percutaneous transluminal coronary angioplasty (PTCA) in eight
      patients with AMI. In the pre-PTCA study, Tc-99m tetrofosmin was injected before
      emergent PTCA. Two weeks after the PTCA, post-PTCA study was performed. As a
      quantitative index of salvaged myocardial mass, salvaged myocardial volume (SMV)
      was defined as the difference of myocardial functional volume between the SPECT
      studies before and after the PTCA. To investigate the clinical significance of
      SMV, SMV was compared with the grade of therapeutic efficacy determined visually
      from pre- and post-PTCA SPECT images and clinical parameters, namely peak
      creatine phosphokinase level (pCK) and the time from the onset of the AMI to
      reperfusion (RPT). RESULTS: SMV showed a significant correlation with the visual
      grade of therapeutic efficacy (r = 0.737, p < 0.037) and a trend toward
      significant correlation with pCK (r = -0.622, p < 0.1). SMVs in early- and late
      reperfusion groups (RPT < or = 6 hr and RPT > 6 hr) were 30.0 +/- 14.0 and -6.2
      +/- 25.5 ml, showing a greater mean SMV value in the early-reperfusion group (p <
      0.07). CONCLUSION: SMV could be used as a quantitative index of salvaged
      myocardial mass for evaluating the therapeutic effect of emergent reperfusion
      therapy.

PMID- 14971620
TI  - Scatter correction on its own increases image contrast in Tl-201 myocardium
      perfusion scintigraphy, but does it also improve diagnostic accuracy?
AB  - Poor and variable spatial resolution of the gamma camera, the movement of the
      heart and, above all, the inclusion of scattered photons in the acquisition data
      contribute to the deterioration of image contrast in 201Tl myocardium perfusion
      studies. Scatter correction algorithms may correct for the latter factor by
      removing (most of) the scattered photons from the acquisition data. METHODS: In
      this study we investigated the contrast changes induced by the Triple Energy
      Window scatter correction method (TEW) applied to clinical 201Tl myocardium
      perfusion studies and its influence on the reading of the images. Stress and rest
      studies of 30 consecutive patients were used for this study. Maximum image
      contrasts were measured between the myocardium and the left ventricular cavity in
      four mid-ventricular short axis slices, as well as between normally and
      abnormally perfused myocardium using bull's-eye displays of the activity within
      the myocardium. To assess image quality and perfusion abnormalities, an
      experienced nuclear medicine physician, blind to patient characteristics,
      visually reviewed all studies. RESULTS: In all individual measurements, the
      maximum contrast after scatter correction was higher than without correction (p <
      0.001). The average increase in contrast between the myocardium and the left
      ventricular cavity was 43% and 48% for stress and rest studies respectively. The
      contrast within the myocardium increased by 25% and 32% respectively. After TEW,
      image quality was rated lower in almost half of the studies, while in only one
      study the quality was rated higher. In stress studies 11 additional perfusion
      defects were observed, with rest studies revealing 15 more defects after TEW, but
      this difference was not significant. Cohen's kappa indicated a moderate agreement
      of the image reading between studies with and without scatter correction.
      CONCLUSION: We conclude that image contrast improves significantly by scatter
      correction. However, image quality decreased as a result of an unfavorable signal
      to-noise ratio. As an overall result, no significant change in the clinical
      outcome of the studies could be shown. Additional training of the readers may be
      required to obtain optimal results.

PMID- 14971621
TI  - An analysis of the physiological FDG uptake pattern in the stomach.
AB  - The purpose of this study was to clarify the normal gastric FDG uptake pattern to
      provide basic information to make an accurate diagnosis of gastric lesions by FDG
      PET. We examined 22 cases, including 9 of malignant lymphoma, 8 of lung cancer, 2
      of esophageal cancer, and 3 of other malignancies. No gastric lesions were
      observed in any of the 22 cases on upper gastrointestinal examinations using
      either barium meal or endoscopic techniques. The intervals between FDG PET and
      the gastrointestinal examination were within one week in all cases. The stomach
      regions were classified into the following three areas: U (upper)-area, M
      (middle)-area, and L (lower)-area. The degree of FDG uptake in these three
      gastric regions was qualitatively evaluated by visual grading into 4 degrees, and
      then a semiquantitative evaluation was carried out using the standardized uptake
      value (SUV). Based on a visual grading evaluation, the mean FDG uptake score in
      the U-, M-, and L-areas was 1.14 +/- 0.96, 0.82 +/- 0.96, and 0.36 +/- 0.49 (mean
      +/- S.D.), respectively. The FDG uptake scores obtained in the three areas were
      significantly different (Friedman test, p < 0.05). Furthermore, the rank order of
      the FDG uptake score in each case (U > or = M > or = L) was found to be
      statistically significant (Cochran-Armitage trend test, p < 0.05). The mean SUVs
      of 11 cases in the three areas were 2.38 +/- 1.03, 1.91 +/- 0.71, and 1.34 +/-
      0.44 (mean +/- S.D.), respectively. The SUV in the U-area was significantly
      higher than that in the L-area (Friedman test, p < 0.05). A significant
      difference in FDG uptake was observed among the three gastric areas, and the FDG
      uptake extent in all cases was U > M > L. In conclusion, the physiological
      gastric FDG uptake was significantly higher at the oral end. A stronger gastric
      FDG uptake at the anal end may therefore be suggestive of a pathological uptake.

PMID- 14971622
TI  - Cognitive changes after acute tryptophan depletion: what can they tell us?

PMID- 14971623
TI  - Saving clinicians' time by delegating routine aspects of therapy to a computer: a
      randomized controlled trial in phobia/panic disorder.
AB  - BACKGROUND: The demand for time-consuming psychotherapy of phobia/panic exceeds
      the supply of trained therapists. Delegating routine therapy aspects to a
      computer might ease this problem. METHOD: Ninety-three out-patients with phobia
      or panic disorder were randomized in a 2: 2 : 1 ratio to have self-exposure
      therapy guided either mainly by a stand-alone computer system (FearFighter) or
      entirely face-to-face by a clinician, or to have mainly computer-guided self
      relaxation as a placebo. Both computer groups (FearFighter and relaxation) had
      brief back-up advice from a clinician. Primary outcome measures were self- and
      blind-assessor ratings of Main Problem and Goals, and Global Phobia. RESULTS:
      Drop-outs occurred significantly more often in the two self-exposure groups (43%
      if mainly computer-guided, 24% if entirely clinician-guided) than with self
      relaxation (6%); the difference between the two self-exposure groups was not
      significant. Even with all drop-outs included, the mainly computer-guided
      exposure group and the relaxation group had 73% less clinician time per patient
      than did the entirely clinician-guided exposure group. The two self-exposure
      groups had comparable improvement and satisfaction at post-treatment and at 1
      month follow-up, while relaxation was ineffective. Mean improvement on the
      primary outcome measures (self- and assessor-rated) was 46% computer, 49%
      clinician, 9% relaxation at post-treatment (week 10) and 58% computer, 53%
      clinician and -4% relaxation at 1-month follow-up (week 14). Mean effect sizes on
      the primary outcome measures were 2.9 computer, 3.5 clinician and 0.5 relaxation
      at post-treatment; and 3.7 computer, 3.5 clinician and 0.5 relaxation at 1-month
      follow-up. The assessor did not rate patients at follow-up. CONCLUSIONS: Despite
      its (non-significantly) higher dropout rate, self-exposure therapy for panic/
      phobia cut clinician time per patient by 73% without losing efficacy when guided
      mainly by a computer rather than entirely by a clinician. The finding needs
      confirmation at a follow-up that is longer and includes a blind assessor. Self
      relaxation had the highest rate of completers but was ineffective.

PMID- 14971624
TI  - Modelling the population cost-effectiveness of current and evidence-based optimal
      treatment for anxiety disorders.
AB  - BACKGROUND: The present paper describes a component of a large population cost
      effectiveness study that aimed to identify the averted burden and economic
      efficiency of current and optimal treatment for the major mental disorders. This
      paper reports on the findings for the anxiety disorders (panic
      disorder/agoraphobia, social phobia, generalized anxiety disorder, post-traumatic
      stress disorder and obsessive compulsive disorder). METHOD: Outcome was
      calculated as averted 'years lived with disability' (YLD), a population summary
      measure of disability burden. Costs were the direct health care costs in 1997-8
      Australian dollars. The cost per YLD averted (efficiency) was calculated for
      those already in contact with the health system for a mental health problem
      (current care) and for a hypothetical optimal care package of evidence-based
      treatment for this same group. Data sources included the Australian National
      Survey of Mental Health and Well-being and published treatment effects and unit
      costs. RESULTS: Current coverage was around 40% for most disorders with the
      exception of social phobia at 21%. Receipt of interventions consistent with
      evidence-based care ranged from 32% of those in contact with services for social
      phobia to 64% for post-traumatic stress disorder. The cost of this care was
      estimated at dollar 400 million, resulting in a cost per YLD averted ranging from
      dollar 7761 for generalized anxiety disorder to dollar 34 389 for
      panic/agoraphobia. Under optimal care, costs remained similar but health gains
      were increased substantially, reducing the cost per YLD to < dollar 20 000 for
      all disorders. CONCLUSIONS: Evidence-based care for anxiety disorders would
      produce greater population health gain at a similar cost to that of current care,
      resulting in a substantial increase in the cost-effectiveness of treatment.

PMID- 14971625
TI  - Is graded exercise better than cognitive behaviour therapy for fatigue? A UK
      randomized trial in primary care.
AB  - BACKGROUND: Patients frequently present with unexplained fatigue in primary care,
      but there have been few treatment trials in this context. We aimed to test
      cognitive behaviour therapy (CBT) and graded exercise therapy (GET) for patients
      presenting to their family doctor with fatigue. Secondly, we described the
      outcome for a cohort of patients who presented to the same doctors with fatigue,
      who received standard care, plus a booklet. METHOD: This was a randomized trial,
      followed by a prospective cohort study. Twenty-two practices in SE England
      referred 144 patients aged 16 to 75 years with over 3 months of unexplained
      fatigue. Self-rated fatigue score, the hospital anxiety and depression rating
      scale, functional impairment, physical step-test performance and causal
      attributions were measured. In the trial six sessions of CBT or GET were randomly
      allocated. RESULTS: In the therapy groups the mean fatigue score decreased by 10
      points (95% confidence interval (CI) = -25 to -15), with no significant
      difference between groups (mean difference = -1.3; CI = -3.9 to 1.3). Fewer
      patients attended for GET. At outcome one-half of patients had clinically
      important fatigue in both randomized groups, but patients in the group offered
      CBT were less anxious. Twenty-seven per cent of the patients met criteria for CFS
      at baseline. Only 25% of this subgroup recovered, compared to 60% of the subgroup
      that did not meet criteria for CFS. CONCLUSIONS: Short courses of GET were not
      superior to CBT for patients consulting with fatigue of over 3 months in primary
      care. CBT was easier 'to sell'. Low recovery in the CFS subgroup suggests that
      brief treatment is too short.

PMID- 14971626
TI  - Randomized controlled trial of Siberian ginseng for chronic fatigue.
AB  - BACKGROUND: Chronic fatigue greatly affects quality of life and is a common
      reason for consulting a physician. Since conventional therapy is often of limited
      help, fatigued patients may use herbal treatments. This randomized controlled
      trial evaluated the effectiveness of Siberian ginseng. METHOD: Subjects were
      recruited from advertisements in Iowa (82%) and members of chronic fatigue
      syndrome support groups (18%). Potential subjects were required to have
      substantial fatigue > or = 6 months with no identifiable cause. The mean change
      in a fatigue measure was compared for placebo and Siberian ginseng at 1 and 2
      months. Comparisons were for all subjects and for subjects with characteristics
      previously identified in the literature as important for categorizing chronic
      fatigue. RESULTS: Ninety-six subjects were randomized to treatment groups, and 76
      provided information at 2 months of follow-up. Fatigue among subjects assigned to
      either placebo or Siberian ginseng was substantially reduced during the study,
      but differences between treatment groups were not statistically significant in
      the full sample. Fatigue severity and duration had a statistically significant
      interaction with response to Siberian ginseng at the P < 0.05 level. Treatment
      was effective at 2 months for 45 subjects with less severe fatigue (P = 0.04
      unadjusted for multiple comparisons) and for 41 subjects with fatigue for > or =
      5 years (P = 0.09 unadjusted for multiple comparisons). CONCLUSION: Overall
      efficacy was not demonstrated. However, the findings of possible efficacy for
      patients with moderate fatigue suggests that further research may be of value.

PMID- 14971627
TI  - A pragmatic cluster randomized controlled trial of an educational intervention
      for GPs in the assessment and management of depression.
AB  - BACKGROUND: General practitioners (GPs) can be provided with effective training
      in the skills to manage depression. However, it remains uncertain whether such
      training achieves health gain for their patients. METHOD: The study aimed to
      measure the health gain from training GPs in skills for the assessment and
      management of depression. The study design was a cluster randomized controlled
      trial. GP participants were assessed for recognition of psychological disorders,
      attitudes to depression, prescribing patterns and experience of psychiatry and
      communication skills training. They were then randomized to receive training at
      baseline or the end of the study. Patients selected by GPs were assessed at
      baseline, 3 and 12 months. The primary outcome was depression status, measured by
      HAM-D. Secondary outcomes were psychiatric symptoms (GHQ-12) quality of life (SF
      36), satisfaction with consultations, and health service use and costs. RESULTS:
      Thirty-eight GPs were recruited and 36 (95%) completed the study. They selected
      318 patients, of whom 189 (59%) were successfully recruited. At 3 months there
      were no significant differences between intervention and control patients on HAM
      D, GHQ-12 or SF-36. At 12 months there was a positive training effect in two
      domains of the SF-36, but no differences in HAM-D, GHQ-12 or health care costs.
      Patients reported trained GPs as somewhat better at listening and understanding
      but not in the other aspects of satisfaction. CONCLUSIONS: Although training
      programmes may improve GPs' skills in managing depression, this does not appear
      to translate into health gain for depressed patients or the health service.

PMID- 14971628
TI  - The Inventory of Depressive Symptomatology, Clinician Rating (IDS-C) and Self
      Report (IDS-SR), and the Quick Inventory of Depressive Symptomatology, Clinician
      Rating (QIDS-C) and Self-Report (QIDS-SR) in public sector patients with mood
      disorders: a psychometric evaluation.
AB  - BACKGROUND: The present study provides additional data on the psychometric
      properties of the 30-item Inventory of Depressive Symptomatology (IDS) and of the
      recently developed Quick Inventory of Depressive Symptomatology (QIDS), a brief
      16-item symptom severity rating scale that was derived from the longer form. Both
      the IDS and QIDS are available in matched clinician-rated (IDS-C30; QIDS-C16) and
      self-report (IDS-SR30; QIDS-SR16) formats. METHOD: The patient samples included
      544 out-patients with major depressive disorder (MDD) and 402 out-patients with
      bipolar disorder (BD) drawn from 19 regionally and ethnicically diverse clinics
      as part of the Texas Medication Algorithm Project (TMAP). Psychometric analyses
      including sensitivity to change with treatment were conducted. RESULTS: Internal
      consistencies (Cronbach's alpha) ranged from 0.81 to 0.94 for all four scales
      (QIDS-C16, QIDS-SR16, IDS-C30 and IDS-SR30) in both MDD and BD patients. Sad
      mood, involvement, energy, concentration and self-outlook had the highest item
      total correlations among patients with MDD and BD across all four scales. QIDS
      SR16 and IDS-SR30 total scores were highly correlated among patients with MDD at
      exit (c = 0.83). QIDS-C16 and IDS-C30 total scores were also highly correlated
      among patients with MDD (c = 0.82) and patients with BD (c = 0.81). The IDS-SR30,
      IDS-C30, QIDS-SR16, and QIDS-C16 were equivalently sensitive to symptom change,
      indicating high concurrent validity for all four scales. High concurrent validity
      was also documented based on the SF-12 Mental Health Summary score for the
      population divided in quintiles based on their IDS or QIDS score. CONCLUSION: The
      QIDS-SR16 and QIDS-C16, as well as the longer 30-item versions, have highly
      acceptable psychometric properties and are treatment sensitive measures of
      symptom severity in depression.

PMID- 14971629
TI  - Cognitive functions in depressive disorders: evidence from a population-based
      study.
AB  - BACKGROUND: Most of the available evidence on the effects of depression is based
      on in- and out-patient samples focusing on individuals suffering from major
      depression. The aims of this study were to examine cognitive functioning in
      population-based samples and to determine whether cognitive performance varies as
      a function of depression subgroup. METHOD: Population-based samples (aged 20-64
      years) with major depression (N = 68), dysthymia (N = 28), mixed anxiety
      depressive disorder (N = 25) and minor depression (N = 66) were examined on a
      variety of cognitive tasks (i.e. episodic memory, verbal fluency, perceptual
      motor speed and mental flexibility). One hundred and seventy-five non-depressed
      individuals served as controls. RESULTS: The total group of depressed individuals
      showed impairments in tasks tapping episodic memory and mental flexibility. Of
      more interest, however, was the observation that the pattern of impairments
      varied as a function of depression subgroup: the major depression and mixed
      anxiety-depressive disorder groups exhibited significant memory dysfunction,
      whereas individuals with dysthymia showed pronounced difficulties in mental
      flexibility. Minor depression did not affect cognitive performance. Verbal
      fluency and perceptual-motor speed were not affected by depression. CONCLUSIONS:
      These results indicate that persons with depressive disorders in the population
      exhibit cognitive impairments in tasks tapping episodic memory and mental
      flexibility and that cognitive impairment varies as a function of depressive
      disorder.

PMID- 14971630
TI  - Effects of the menstrual cycle on mood, neurocognitive and neuroendocrine
      function in healthy premenopausal women.
AB  - BACKGROUND: Neurocognitive functioning may be impaired in the luteal phase of the
      menstrual cycle due to associated changes in hypothalamic-pituitary adrenal (HPA)
      axis function. This study examines the relationship between changes in
      neurocognition and HPA axis function in different phases of the menstrual cycle.
      METHOD: Fifteen female volunteers, free from psychiatric history and hormonal
      medication were tested twice, during mid-follicular and late-luteal phases in a
      randomized, crossover design. Mood, neurocognitive function, and basal cortisol
      and dehydroepiandrosterone (DHEA) were profiled. RESULTS: Relative to the
      follicular phase, verbal fluency was impaired in the luteal phase and reaction
      times speeded on a continuous performance task, without affecting overall
      accuracy. 'Hedonic' scores on the UWIST-MACL scale were decreased in the luteal
      phase. There was also evidence of changes in the function of the HPA axis, with
      24 h urinary cortisol concentrations and salivary DHEA levels being significantly
      lower during the luteal phase. CONCLUSIONS: These data suggest that luteal phase
      HPA axis function is lower than in the follicular phase in premenopausal healthy
      women. This putative biological difference may be important for our understanding
      of the aetiopathogenesis of menstrually related mood change and neurocognitive
      disturbance.

PMID- 14971631
TI  - Lower high-density lipoprotein cholesterol and increased omega-6 polyunsaturated
      fatty acids in first-degree relatives of bipolar patients.
AB  - BACKGROUND: Lower serum high-density lipoprotein cholesterol and increased ratio
      of omega-6/omega-3 fatty acids have been reported in unipolar and bipolar
      depressed patients. Changes in cholesterol and fatty acids have been suggested to
      affect membrane viscosity and consequently serotonergic neurotransmitter
      expression. The goal of this study was to investigate whether lower baseline
      cholesterol and increased omega-6 and lower omega-3 fatty acids are present in
      healthy first-degree relatives of bipolar patients compared with controls and
      whether these changes were associated with neuroendocrine responses to an i.v.
      tryptophan challenge or mood. METHOD: Baseline cholesterol, fatty acids and mood
      were determined in healthy first-degree relatives of patients with bipolar
      disorders (N = 30) and healthy matched controls (N = 15) (parallel-group design).
      Prolactin and cortisol were measured following tryptophan infusion. RESULTS:
      First-degree relatives showed significantly lower plasma high-density lipoprotein
      cholesterol and increased total omega-6 fatty acids in phospholipids. Lower total
      omega-3 and higher total omega-6 fatty acids in phospholipids were positively
      correlated with peak prolactin response to tryptophan. Lower total omega-3 fatty
      acids in phospholipids and cholesteryl esters were associated with lower mood.
      CONCLUSIONS: Abnormalities of lower plasma high-density lipoprotein cholesterol
      and increased total omega-6 fatty acids in phospholipids in these subjects are in
      agreement with findings in bipolar and major depressed patients. Changes in fatty
      acids show an association with central serotonergic parameters. It is suggested
      that these abnormalities in cholesterol and fatty acids may constitute a trait
      marker for bipolar disorders.

PMID- 14971632
TI  - Bulimia nervosa with co-morbid avoidant personality disorder: behavioural
      characteristics and serotonergic function.
AB  - BACKGROUND: Separate lines of research link lowered serotonin tone to
      interpersonal submissiveness and bulimia nervosa (BN). We explored the impact of
      co-morbid avoidant personality disorder (APD), as a proxy for submissiveness, on
      behavioural inhibition and serotonin function in women with BN. METHOD:
      Participants included women with BN with co-morbid APD (BNA +, N = 13); women
      with BN but without APD (BNA-, N = 23), and control women with neither BN nor APD
      (N = 23). The women were assessed for psychopathological tendencies and eating
      disorder symptoms, and participated in a computerized laboratory task that
      measured behavioural inhibition and disinhibition. Participants also provided
      blood samples for measurement of serial prolactin responses following oral
      administration of the partial 5-HT agonist meta-chlorophenylpiperazine (m-CPP).
      RESULTS: The BNA+ group had higher scores than the other groups on self-report
      measures of submissiveness, social avoidance, restricted emotional expression,
      affective instability and self-harming behaviours. Compared with the other
      groups, the BNA+ group tended to be more inhibited under cues for punishment on
      the computerized task and to have blunted prolactin response following m-CPP. The
      bulimic groups did not differ from each other on current eating symptoms or on
      frequencies of other mental disorders. CONCLUSIONS: Findings indicate that women
      with BN and co-morbid APD may be characterized by interpersonal submissiveness
      and avoidance, affective instability, self-harm, behavioural inhibition in
      response to threat and lower sensitivity to serotonergic activation. These
      findings may indicate common, serotonergic factors, associated with social
      submissiveness, behavioural inhibition to threat and BN.

PMID- 14971633
TI  - Treatment response in late-onset depression: relationship to neuropsychological,
      neuroradiological and vascular risk factors.
AB  - BACKGROUND: Late-onset depressive disorder is associated with white matter
      lesions and neuropsychological deficits that in some studies are linked to a
      poorer outcome for depression. Some white matter lesions may be vascular in
      origin. This study investigated the relationship between response or non-response
      to antidepressant monotherapy and neuropsychological function, structural brain
      measures and vascular factors. METHOD: This was a case control study. Fifty
      patients with late-onset major depressive disorder (29 who were responders to
      antidepressant monotherapy and 21 who were not) were compared with 35 non
      depressed control subjects. Measures included assessment of vascular risk
      factors, neuropsychological testing and a magnetic resonance imaging (MRI) scan.
      RESULTS: After adjustment for depressed mood and medication at evaluation, both
      patient groups had significantly more impairment compared to control subjects on
      verbal learning tasks involving immediate or delayed recall. Patients who did not
      respond to antidepressant monotherapy had significantly poorer performance than
      controls on tests involving visuospatial ability, language, word recognition and
      tests of executive function, whereas there were no differences between control
      subjects and responders. On two tests of executive function (verbal fluency and
      the Stroop test) non-responders scored significantly worse than responders. There
      were no significant group differences on MRI measures of atrophy or of white
      matter lesions apart from a higher periventricular hyperintensity score in non
      responders compared to controls. There were no group differences on measures of
      vascular disease. CONCLUSION: The results lend support to the emerging evidence
      that resistance to treatment in late-onset depression may be associated with
      impaired executive function. Subtle cerebrovascular mechanisms may be involved.

PMID- 14971634
TI  - Suicide at 50 years of age and older: perceived physical illness, family discord
      and financial strain.
AB  - BACKGROUND: Mental disorders amplify suicide risk across the lifecourse, but most
      people with mental disorder do not take their own lives. Few controlled studies
      have examined the contribution of stressors to suicide risk. METHOD: A case
      control design was used to compare 86 suicides and 86 controls aged 50 years and
      older, matched on age, gender, race and county of residence. Structured
      interviews were conducted with proxy respondents for suicides and controls.
      RESULTS: Perceived physical illness, family discord and employment change
      amplified suicide risk after controlling for sociodemographic covariates and
      mental disorders that developed > or = 1 year prior to death/interview. Only the
      effect of physical illness (OR 6.24, 95% CI 1.28-51.284) persisted after
      controlling for all active mental disorders. CONCLUSIONS: Interventions to
      decrease the likelihood of financial stress and to help families manage discord
      and severe physical illness may effectively reduce suicides among middle-aged and
      older adults.

PMID- 14971635
TI  - Does diagnosis determine delivery? The Islington study of older people's needs
      and health care costs.
AB  - BACKGROUND: Little is known about the factors associated with the receipt of care
      by older people. This study investigates the use. costs and factors associated
      with service usage among people aged 65 or older living in inner London. METHOD:
      A community-based survey, using questionnaires, examined psychiatric and physical
      morbidity, formal and informal care. The relationships between demographic,
      pathological features and the costs of health and social care were explored using
      multivariate regression. RESULTS: A total of 1085 people were interviewed at home
      of these 18% did not receive any service at all. The total cost of services per
      week for people with dementia was pound 109, with activity limitation pound 14
      and with depression pound 12. The greatest effect of physical limitation was on
      the receipt of social care. Dementia had the strongest effect on receipt of
      social care services. Depression increased health care costs to a much greater
      degree than social care costs. Despite presenting to services, black elders
      received significantly less health care than other people with the same needs.
      Older people living alone were more likely to receive social care support and
      appeared less likely to use health services. CONCLUSIONS: Physical dependency
      significantly affects both health and social care costs. Increasing cognitive
      impairment mainly leads to increasing social care costs. Overall costs are
      increased by physical dependency, dementia, depression, subjective health
      problems, living alone and are negatively affected by being black.

PMID- 14971636
TI  - Assessing mental health in primary care research using standardized scales: can
      it be carried out over the telephone?
AB  - BACKGROUND: Telephone interviewing has economic and logistical advantages but has
      not been widely used in the UK. Most studies comparing face-to-face and telephone
      psychiatric assessment have been carried out in the US, often restricted to a
      population with known psychiatric disorder and involving comparisons between two
      separate sample groups rather than repeat interviews with the same group. The aim
      of the present study was to compare face-to-face and telephone administration of
      the 12-item General Health Questionnaire and the Revised Clinical Interview
      Schedule in a UK general practice sample. METHOD: Ninety-eight consecutive
      attenders at two general practices were assessed twice within 48 h. The order of
      face-to-face and telephone interviews was alternated. RESULTS: There was no
      evidence that the mode of administration led to a bias in scores on the CIS-R.
      For the GHQ, those aged over 60 tended to score higher on the telephone. There
      was good agreement between face-to-face and telephone scores for both GHQ and CIS
      R and good agreement for case definition. Participants had a strong preference
      for face-to-face interviews. CONCLUSIONS: Telephone assessment of mental health
      using the GHQ and CIS-R is a reasonable method to be used in primary care
      research in the UK with the limitation that telephone responses from older people
      might be different from face-to-face assessments for the GHQ. However, telephone
      interviewing appeared less acceptable and should probably be used in the context
      of established or ongoing personal contact between researcher and subject.

PMID- 14971637
TI  - Problem-solving in suicide attempters.
AB  - BACKGROUND: Recent research studies on the psychological processes underlying
      suicidal behaviour have highlighted deficits in social problem-solving ability,
      and suggest that suicide attempters may, in addition, be passive problem-solvers.
      The aim of this study was to examine problem-solving in suicide attempters
      (including passivity) and to see whether the deficits are mood-dependent. METHOD:
      Two groups, a suicide attempter group and a non-suicidal psychiatric control
      group completed measures of depression, hopelessness, suicidal ideation and
      social problem-solving ability shortly after admission, and again 6 weeks later.
      In addition, a non-psychiatric control group provided baseline data at a single
      time point. RESULTS: The suicide attempter group displayed poorer problem-solving
      ability than matched psychiatric controls and this difference persisted despite
      change in mood. However, although suicidal patients were more passive in their
      problem-solving style than non-psychiatric controls, they were not significantly
      more passive than psychiatric controls. Problem-solving did not change with
      improving mood. CONCLUSIONS: Although passivity is not unique to suicidal
      patients, in combination with the smaller number and less effective alternatives
      generated, it may increase vulnerability.

PMID- 14971638
TI  - Further neuroendocrine evidence of enhanced vasopressin V3 receptor responses in
      melancholic depression.
AB  - BACKGROUND: In situations of chronic stress vasopressin plays an important role
      in regulating the hypothalamic-pituitary adrenal axis. The aim of the current
      study was to investigate the role of anterior pituitary vasopressin V3 receptors
      in maintaining the hypercortisolism seen in melancholic depression. METHOD:
      Fourteen patients with major depression and 14 age- and sex-matched healthy
      comparison subjects were recruited. Desmopressin (ddAVP) 10 microg was given
      intravenously and ACTH and cortisol release was monitored for 120 min. RESULTS:
      The mean +/- S.E.M. ACTH response in the depressives was 28.4 +/- 4.3 ng/l and in
      the healthy subjects was 18.8 +/- 4.9 ng/l (P = 0.04). The mean +/- S.E.M.
      cortisol response in the depressives was 261.8 +/- 46.5 nmol/l and in the healthy
      subjects was 107.3 +/- 26.1 nmol/l (P < 0.01). CONCLUSIONS: Patients with major
      depression have augmented ACTH and cortisol responses to desmopressin indicating
      enhanced V3 responsivity.

PMID- 14971639
TI  - Patients with obsessive-compulsive disorder (OCD) displayed cognitive deficits
      consistent with a dysfunction of the dorsolateral-striatal circuit.

PMID- 14971640
TI  - Metal-induced toxicity, carcinogenesis, mechanisms and cellular responses.
AB  - A wide variety of metals have been reported to act as mutagenic and carcinogenic
      agents in both human and animal studies. The underlying mechanisms are being
      extensively investigated. Recently, a new sub-discipline of molecular
      carcinogenesis has surfaced and new techniques and instruments are being
      developed which allow exploration of the complex biological relationships and
      signaling pathways involved in response to metal exposure at the molecular level.
      The 2nd Conference on Molecular Mechanisms of Metal Toxicity and Carcinogenesis
      was held at NIOSH in Morgantown, West Virginia, Sept. 8-11, 2002. One hundred
      thirty scientist from sixteen countries presented their novel findings and
      investigations of metal-induced carcinogenesis. The conference focused on state
      of-the-art research and developments in metal toxicity and carcinogenesis.
      Emphasis was placed on delineating molecular mechanisms involved in free radical
      effects, cellular uptake, signaling pathways/interaction, dose response,
      biomarkers, and resistance mechanisms. This article reviews some of the novel
      information presented at the conference and discusses future avenues of research
      in this field.

PMID- 14971641
TI  - Toxicokinetic and genomic analysis of chronic arsenic exposure in multidrug
      resistance mdr1a/1b(-/-) double knockout mice.
AB  - Multidrug-resistance gene knockout mdr1a/1b(-/-) mice, which are deficient in P
      glycoproteins, are more sensitive than wild-type (WT) mice to acute arsenic
      toxicity. This study assessed toxic manifestations of chronic oral arsenic in
      mdr1a/1b(-/-) mice, including oxidative stress and altered gene expression, and
      investigated altered toxicokinetics as a potential basis of enhanced arsenic
      toxicity. Thus, mdr1a/1b(-/-) and WT mice were exposed to sodium arsenite (0-80
      ppm as arsenic) in the drinking water for 10 weeks at which time hepatic arsenic
      accumulation, lipid peroxidation (LPO), redox status and change in gene
      expression level were assessed. All mice survived the arsenic exposure, but body
      weight gain in the highest dose group was reduced in both mdr1a/1b(-/-) and WT
      mice. Arsenic induced pathological changes, elevated LPO levels and enhanced
      glutathione S-transferase (GST) activity, in the liver to a greater extent in
      mdr1a/1b(-/-) than in WT mice. Arsenic also decreased Cu/Zn superoxide dismutase
      activity in both mdr1a/1b(-/-) and WT mice. The expressions of certain genes,
      such as those encoding cell proliferation, GST, acute-phase proteins and
      metabolic enzymes, were modestly altered in arsenic-exposed mice. The expression
      of cyclin D1, a potential hepatic oncogene, was enhanced in arsenic-exposed
      mdr1a/1b(-/-) mice only. At the highest level of exposure, hepatic arsenic
      content was higher in mdr1a/1b(-/-) than in WT mice, suggesting that enhanced
      accumulation due to transport deficiency may, in part, account for the enhanced
      toxicity in these mice. In summary, this study shows that chronic arsenic
      toxicity, including liver pathology and oxidative stress, is enhanced in
      mdr1a/1b(-/-) mice, possibly due to enhanced accumulation of arsenic as a result
      of transport system deficiency.

PMID- 14971642
TI  - Arsenite induces p70S6K1 activation and HIF-1alpha expression in prostate cancer
      cells.
AB  - Arsenite is ubiquitous in the environment, particularly in the form of
      contaminated water. Although this metal is a known human carcinogen, its exact
      mechanism of action remains unclear. P70S6K1 phosphorylates the ribosomal 40S
      protein leading to increased protein translation, and is an important regulator
      of cell growth and proliferation. Hypoxia inducible factor-1 (HIF-1) is a basic
      helix-loop-helix transcription factor composed of two subunits, HIF-1alpha and
      HIF-1beta. HIF-1 activates the transcription of a number of genes that mediate
      angiogenesis and tumor formation. In this study we demonstrated that arsenite
      treatment increased levels of p70S6K1 phosphorylation and p70S6K1 activity in a
      PI3K and mTOR sensitive manner. We have also shown that arsenite specifically
      induces HIF-1alpha, but not HIF-1beta, protein levels in prostate cancer cells in
      a mTOR-dependent manner.

PMID- 14971643
TI  - p53 expression in circulating lymphocytes of non-melanoma skin cancer patients
      from an arsenic contaminated region in Mexico. A pilot study.
AB  - Arsenic is a common environmental toxicant and epidemiological studies associate
      arsenic exposure with various pathologic disorders and several types of cancer.
      Skin cancers are the most common arsenic-induced neoplasias and the prevalence of
      skin lesions has been reported to be significantly elevated in individuals
      exposed to arsenic via drinking water in Mexico. Being lymphocytes the main cells
      used for human monitoring, we evaluated the expression of p53 protein in the
      lymphocytes from 44 healthy individuals and 19 samples from individuals living in
      a chronic arsenicism endemic region. Of the latter group, 12 individuals had non
      melanoma skin cancer and 9 of them expressed p53 in the circulating lymphocytes,
      whereas only one of the 7 non-cancer arsenic exposed individuals expressed it. In
      the healthy non-arsenic exposed group only one from 44 individuals expressed the
      protein. These results suggest a clear relationship between non-melanoma skin
      cancer and p53 expression in circulating lymphocytes. p53 expression in
      circulating lymphocytes should be evaluated as a potential biomarker of effect or
      susceptibility.

PMID- 14971644
TI  - Arsenite induces HIF-1alpha and VEGF through PI3K, Akt and reactive oxygen
      species in DU145 human prostate carcinoma cells.
AB  - Arsenite is widely distributed environmental toxicant in water, food and air. It
      is a known human carcinogen, which is strongly associated with human cancers
      originated from liver, nasal cavity, lung, skin, bladder, kidney, and prostate.
      In this study, we investigated whether arsenite induces expression of hypoxia
      inducible factor 1 (HIF-1). HIF-1 is a heterodimeric basic helix-loop-helix
      transcription factor, composed of HIF-1alpha and HIF-1beta/ARNT subunits; and is
      involved in tumor growth and angiogenesis. Here we demonstrate that arsenite
      induces the expression of HIF-1alpha but not HIF-1beta subunit in DU145 human
      prostate carcinoma cells. Arsenite also increases the expression of VEGF through
      the induction of HIF-1. We also found that arsenite activates PI3K and Akt that
      are required for arsenite-induced expression of HIF-1alpha and VEGF. The
      induction of HIF-1 and VEGF by arsenite can not be inhibited by MAP kinase
      inhibitors. Arsenite causes production of reactive oxygen species (ROS). The
      major species of ROS required for the induction of HIF-1 and VEGF is H2O2. These
      data indicate that the arsenite-induced activation of PI3K/Akt signaling and the
      expression of HIF-1 and VEGF through the generation of ROS could be an important
      mechanism in the arsenite-induced carcinogenesis.

PMID- 14971645
TI  - Arsenic toxicity, mutagenesis, and carcinogenesis--a health risk assessment and
      management approach.
AB  - A comprehensive analysis of published data indicates that arsenic exposure
      induces cardiovascular diseases, developmental abnormalities, neurologic and
      neurobehavioral disorders, diabetes, hearing loss, hematologic disorders, and
      various types of cancer. Although exposure may occur via the dermal, and
      parenteral routes, the main pathways of exposure include ingestion, and
      inhalation. The severity of adverse health effects is related to the chemical
      form of arsenic, and is also time- and dose-dependent. Recent reports have
      pointed out that arsenic poisoning appears to be one of the major public health
      problems of pandemic nature. Acute and chronic exposure to arsenic has been
      reported in several countries of the world where a large proportion of drinking
      water (groundwater) is contaminated with high concentrations of arsenic. Research
      has also pointed significantly higher standardized mortality rates for cancers of
      the bladder, kidney, skin, liver, and colon in many areas of arsenic pollution.
      There is therefore a great need for developing a comprehensive health risk
      assessment (RA) concept that should be used by public health officials and
      environmental managers for an effective management of the health effects
      associated with arsenic exposure. With a special emphasis on arsenic toxicity,
      mutagenesis, and carcinogenesis, this paper is aimed at using the National
      Academy of Science's RA framework as a guide, for developing a RA paradigm for
      arsenic based on a comprehensive analysis of the currently available scientific
      information on its physical and chemical properties, production and use, fate and
      transport, toxicokinetics, systemic and carcinogenic health effects, regulatory
      and health guidelines, analytical guidelines and treatment technologies.

PMID- 14971648
TI  - Variability in sensitivity to arsenite does not correlate with arsenic
      accumulation rate in normal human lymphoblasts.
AB  - Arsenic is a common environmental contaminant of our air, water and food, but not
      every individual who drinks arsenic-contaminated water shows clinical signs of
      toxicity. Large inter-individual variations are also found in arsenite-induced
      aneuploidy, chromosome aberrations and sister chromatid exchanges in peripheral
      blood lymphocytes from different human donors. Lymphoblasts are virally
      immortalized lymphocytes that retain most of the properties of lymphocytes.
      Individual lymphoblast cell lines retained their arsenite sensitivity after
      cryopreservation and subsequent revival. We measured the accumulation of 73[As]
      arsenite into lymphoblast lines derived from 11 normal individuals. Arsenite
      accumulation rate varied 6.3 fold between the slowest and the fastest subjects.
      Assays in 14 lymphoblast lines showed variability to the toxic effects of
      arsenite, as measured by growth inhibition. Lymphoblast lines also vary with
      regard to their growth rates, but there is no relationship between growth rate
      and arsenite sensitivity. Surprisingly, we also found no correlation between
      arsenite accumulation rate and cellular sensitivity to growth inhibition,
      suggesting that the arsenite accumulation rate may not be the main determinant of
      cellular sensitivity to arsenic. We were also unable to detect evidence for a
      human homolog for the yeast arsenite efflux gene ACR3, using RT-PCR.

PMID- 14971647
TI  - Oxidative mechanism of arsenic toxicity and carcinogenesis.
AB  - Arsenic is a known toxin and carcinogen that is present in industrial settings
      and in the environment. The mechanisms of disease initiation and progression are
      not fully understood. In the last a few years, there has been increasing evidence
      of the correlation between the generation of reactive oxygen species (ROS), DNA
      damage, tumor promotion, and arsenic exposure. This article summarizes the
      current literature on the arsenic mediated generation of ROS and reactive
      nitrogen species (RNS) in various biological systems. This article also discusses
      the role of ROS and RNS in arsenic-induced DNA damage and activation of oxidative
      sensitive gene expression.

PMID- 14971646
TI  - Molecular mechanisms of arsenic carcinogenesis.
AB  - Arsenic is a metalloid compound that is widely distributed in the environment.
      Human exposure of this compound has been associated with increased cancer
      incidence. Although the exact mechanisms remain to be investigated, numerous
      carcinogenic pathways have been proposed. Potential carcinogenic actions for
      arsenic include oxidative stress, genotoxic damage, DNA repair inhibition,
      epigenetic events, and activation of certain signal transduction pathways leading
      to abberrant gene expression. In this article, we summarize current knowledge on
      the molecular mechanisms of arsenic carcinogenesis with an emphasis on ROS and
      signal transduction pathways.

PMID- 14971649
TI  - The gender differences in health effects of environmental cadmium exposure and
      potential mechanisms.
AB  - On a viewpoint of gender differences in Cd body burden and its health effects, we
      reviewed the population-based research including our own which conducted in
      Japan, Thailand, Australia, Poland, Belgium and Sweden to assess health effects
      of human exposure to environmental cadmium and their potential mechanisms. As a
      result, six risk factors in Cd health effects in women have been identified; (1)
      more serious type of renal tubular dysfunction, (2) difference in calcium
      metabolism and its regulatory hormones, (3) kidney sensitivity; difference in
      P450 phenotype, (4) pregnancy, (5) body iron store status, and (6) genetic
      factors. Further studies of Cd toxicity targeted to women would now appear
      necessary.

PMID- 14971650
TI  - Up-regulation of expression of translation factors--a novel molecular mechanism
      for cadmium carcinogenesis.
AB  - The molecular mechanisms potentially responsible for cadmium carcinogenesis were
      investigated by differential gene expression analysis of Balb/c-3T3 cells
      morphologically transformed with cadmium chloride. Differential display analysis
      of gene expression revealed overexpression of mouse Translation Initiation Factor
      3 (TIF3; GenBank Accession Number AF 271072) and Translation Elongation Factor
      1delta (TEF-1delta; GenBank Accession Number AF 304351) in the transformed cells
      compared with the control cells. The full length cDNAs for TIF3 and TEF-1delta
      were cloned and sequenced. Transfection of mammalian cells with an expression
      vector containing either TIF3 or TEF-1delta cDNA resulted in overexpression of
      the encoded protein. Overexpression of the cDNA-encoded TIF3 and TEF-1delta
      proteins in NIH3T3 cells was oncogenic as evidenced by the appearance of
      transformed foci capable of anchorage-independent growth on soft agar and
      tumorigenesis in nude mouse. Blocking the translation of TIF3 and TEF-1delta
      proteins using the corresponding antisense mRNA resulted in a significant
      reversal of the oncogenic potential of cadmium transformed Balb/c-3T3 cells as
      evidenced from the suppression of anchorage-independent growth on soft agar and
      diminished tumorigenesis in nude mouse. These findings demonstrate that the up
      regulation of expression of TIF3 and TEF-1delta is a novel molecular mechanism
      responsible, at least in part, for cadmium carcinogenesis.

PMID- 14971651
TI  - Telomerase-mediated lifespan extension of human bronchial cells does not affect
      hexavalent chromium-induced cytotoxicity or genotoxicity.
AB  - Hexavalent chromium (Cr(VI)) is a metal of increasing public health concern, as
      exposure to it is widespread and it is a well-established cause of human
      bronchial carcinomas and fibrosarcomas. The water-insoluble Cr(VI) salts are
      potent carcinogens compared to the water soluble salts; yet the genotoxic
      mechanisms of both may be mediated by soluble Cr(VI) ions. Currently, these
      mechanisms are poorly understood. Emerging evidence suggests that initial cell
      culture models used to study the general toxicity of Cr(VI) may be suboptimal for
      investigating mechanisms specific to human bronchial cells. Accordingly, we have
      developed a new model system of human bronchial cells by introducing hTERT, the
      catalytic subunit of human telomerase, into primary human bronchial fibroblasts
      (PHBF). We have isolated a stable, clonally derived cell line, WHTBF-6, that
      demonstrate reconstitution of telomerase activity and maintenance of telomere
      lengths with increasing culture age. WHTBF-6 has been characterized as having an
      extended in vitro lifespan, a normal growth rate, a normal diploid karyotype that
      is maintained over time, and exhibits serum-dependent contact-inhibited anchorage
      dependent growth. Moreover, we find that both particulate and soluble hexavalent
      chromium induce a pattern and degree of cytotoxicity and clastogenicity in WHTBF
      6 that is similar to the parental PHBF cells. Because telomerase does not
      compromise growth or the response to Cr(VI), our results indicate that this is an
      excellent system for studying the mechanisms of Cr(VI) and potentially other
      carcinogens implicated in the development of lung cancer.

PMID- 14971652
TI  - Crystalline and water soluble Cr(4+) and Cr(5+) model compounds for chromium
      toxicity studies.
AB  - We discuss two complexes of Cr(4+) for their possible utility as models for Cr
      toxicity studies. They are Cr(dien)(O2)2(.)H2O (dien = diethylenetriamine) and
      Cr(NH3)3(O2)2, which have been recently characterized by x-ray diffraction and
      magnetic techniques. We present their optical and infrared absorption spectra as
      quick aids in their identification procedure. We also summarize the general
      properties of some well-characterized Cr(5+) compounds. All of these compounds
      are water soluble with the Cr(5+) samples being fairly stable in basic solutions.
      They can all be prepared as pure crystals with a shelf life of over 2 years when
      stored in a refrigerator.

PMID- 14971653
TI  - Role of reactive oxygen species and Cr(VI) in Ras-mediated signal transduction.
AB  - Previous studies have shown that a constitutively active isoform of Ras is able
      to produce superoxide radical (O2(-)). The present study investigate the
      mechanisms by which O2(-) radical mediates signals from Ras protein to the
      nucleus, leading to cellular responses such as apoptosis in Cr(VI)-stimulated
      cells. Two human prostate tumor cell lines, Ras(+), which overexpresses Ras, and
      Ras(-), which has a normal Ras level, were utilized. Compared to Ras(-) cells,
      Ras(+) cells exhibited higher susceptibility to apoptosis induced by Cr(VI).
      Catalase, sodium formate, and deferoxamine inhibited Cr(VI)-induced apoptosis.
      Similar differences were observed in both cellular DNA damage and the activation
      of p53 protein. The differences in Cr(VI)-induced cell responses in Ras(+) and
      Ras(-) cells were due to differences in the generation of free radicals between
      these two cells. ESR spin trapping measurements showed that Ras(+) cells
      generated more hydroxyl radical ((.)OH), O2(-) radical, and Cr(V) than Ras(-)
      cells following Cr(VI) stimulation. The generation of the reactive oxygen species
      (ROS) can be abolished by the addition of superoxide dismutase (SOD) or if the
      experiment were carried out in an argon atmosphere. Catalase inhibited spin
      adduct signals but was much less potent than SOD. The mechanism of ROS generation
      in Cr(VI)-stimulated Ras(+) cells involves the reduction of molecular oxygen to
      O2(-) radical by a flavoenzyme-containing NADPH oxidase complex as shown by
      oxygen consumption and diphenylene iodonium (DPI) inhibition. Results shown above
      support the following conclusions: (a) Ras protein mediates O2(-) radical
      generation through reduction of molecular oxygen by NADPH oxidase in Cr(VI)
      stimulated cells. (b) The O2(-) radical and Cr(VI) produce other reactive
      species, including H2O2, OH radical, and Cr(V) through O2(-) dismutation and
      Haber-Weiss type of reactions. (c) Among these reactive species, (.)OH radical is
      responsible for the further transduction of signals from Ras to the nucleus,
      leading to various cell responses.

PMID- 14971654
TI  - NF-kappaB prevents cells from undergoing Cr(VI)-induced apoptosis.
AB  - The transcription factor NF-kappaB has been reported to prevent cells from
      undergoing apoptosis as well as promote cell apoptosis. To investigate the role
      of NF-kappaB in Cr(VI)-induced apoptosis, two cell lines were developed from
      human bronchial epithelial BEAS-2B cells: IKK cells, which were stably
      transfected with IkappaBalpha expression vector, that have normal NF-kappaB
      activity, and KM cells, which were stably transfected with mutated IkappaBalpha
      kinase expression vector, that exhibit very little NF-kappaB activity. With
      Cr(VI) stimulation, KM cells, but not IKK cells, exhibited substantial cell
      death. Cell morphological and TUNEL analyses indicated that the KM cells showed
      apoptotic features. These results suggest that NF-kappaB activation is required
      to prevent the cells from undergoing Cr(VI)-induced apoptosis.

PMID- 14971655
TI  - Induction of pro-apoptotic and cell cycle-inhibiting genes in chromium (VI)
      treated human lung fibroblasts: lack of effect of ERK.
AB  - Cell proliferation and apoptosis are controlled by tightly orchestrated signaling
      pathways that culminate in transcriptional activation/repression of multiple
      proteins. Dysregulation of cell cycle and/or apoptosis control may lead to
      genomic instability, neoplastic transformation and tumor progression. Under
      certain conditions, some hexavalent chromium [Cr(VI)] compounds are toxic and
      carcinogenic in the human respiratory tract, and we have shown that they induce
      apoptosis and/or cell cycle arrest in a p53-dependent fashion. There is
      increasing evidence linking extracellular signal-regulated kinase (ERK)
      activation with the DNA damage response, by both p53-dependent and -independent
      mechanisms. Here, the aim was to study the effect of Cr(VI) transcriptional
      regulation of key cell cycle inhibitors and pro- and anti-apoptotic proteins, as
      well as the role of ERK activation in the Cr(VI) genotoxic response. Diploid
      human lung fibroblasts were incubated with 3-9 uM Na2CrO4, and RNA was isolated
      at 4, 8, and 24 h, as well as 24 h after Cr(VI) exposure was terminated
      (recovery). mRNA expression was quantitated by RNase protection assay with a 32P
      labeled multi-transcript probe containing gene sequences for the cdk inhibitors,
      p21waf1/cip1, p27kip1, p16INK4a, p15INK4b; the pro-apoptotic proteins bcl-XS and
      bax; the anti-apoptotic proteins bcl-W, bcl-XL, and bcl2, GADD45, and cyclin A.
      In general, bcl-W and bcl-XL expression were both downregulated after Cr
      exposure, to around 50% at 24 h, which was more pronounced after the recovery
      period. At Cr(VI) concentrations < or = 6 uM, bcl2 expression was upregulated. Of
      particular interest is that bax expression was reduced, in a dose and time
      dependent fashion, however that of bcl-XS was elevated by nearly 3-fold after 8
      h, and declined to control levels at the end of the recovery period. Expression
      of GADD45 and p21 were both upregulated by 2-fold at 8 h, but declined to control
      levels during recovery. Neither the expression of p27 nor that of p16 were
      apparently affected by Cr(VI) exposure, however the expression of p15 was
      markedly increased after exposure to all concentrations of Cr(VI). Finally, the
      expression of cyclin A was decreased after 24 h Cr(VI) exposure. Cr(VI) induced a
      transient burst of ERK activity (2-6-fold over control) around 0.5-3 h after
      exposure. However, inhibition of ERK activation with PD98059 had no effect on the
      Cr-induced alterations in gene expression. Moreover, Cr(VI)-induced clonogenic
      lethality, as assessed after 24 h exposure to 1 and 2 uM Cr(VI), was also not
      affected by ERK inhibition. These data suggest that both p53-dependent and 
      independent apoptotic and growth-inhibitory pathways are markedly affected by
      Cr(VI) exposure. However, the ability of Cr(VI) to affect key apoptotic and
      growth arresting genes, and thus clonogenic lethality, appears to be independent
      of ERK. Continued investigation into the cellular and molecular mechanisms of
      Cr(VI)-induced cell cycle and apoptosis control should further the understanding
      of Cr(VI)-associated carcinogenesis.

PMID- 14971656
TI  - Mechanisms of chromium-induced suppression of RNA synthesis in cellular and cell
      free systems: relationship to RNA polymerase arrest.
AB  - Chromium(VI) (Cr(VI)) can suppress both DNA replication and transcription as a
      result of chromium (Cr)-induced DNA damage. While progress has been made in the
      characterization of Cr-induced DNA polymerase arresting lesions, very little
      information is available on the inhibition of transcription by this metal. The
      aim of the present study was to identify the molecular mechanisms involved in the
      reduction of RNA synthesis by Cr. Following treatment with a moderately cytotoxic
      dose (approximately LC50) of Cr(VI) (150 microM for 2 h), total RNA synthesis was
      initially suppressed in CHO cells and recovered to control levels within 72 h
      post-treatment. In vitro nuclear run-on transcription assays of nuclei isolated
      from Cr(VI)-treated cells showed a similar amount of RNA synthesis suppression as
      observed in intact cells. Qualitative analysis of nascent transcripts revealed a
      general, concentration-dependent reduction in size suggesting that
      transcriptional elongation was inhibited following Cr-treatment. Transcriptional
      initiation in these nuclei was also reduced. To better determine whether
      transcriptional suppression was related to Cr-induced DNA damage we examined the
      transcriptional activity of T7 RNA polymerase on Cr(III)-treated plasmid DNA.
      Treatment of pGEM3Z-TS DNA with Cr(III) resulted in transcriptional arrest which
      occurred primarily at GC-rich and palindromic regions. However, in contrast to
      the cellular data, transcriptional initiation was unaffected in the in vitro
      transcription arrest assays. Taken together, these results suggest that the
      suppression of RNA synthesis by Cr is related to chromium-induced template DNA
      damage which prevents elongation leading to premature RNA polymerase arrest.

PMID- 14971657
TI  - Lead-induced cytotoxicity and transcriptional activation of stress genes in human
      liver carcinoma (HepG2) cells.
AB  - Lead is a non-essential element that exhibits a high degree of toxicity,
      especially in children. Most research on lead has focused on its effects on organ
      systems such as the nervous system, the red blood cells, and the kidneys which
      are considered to be the primary targets of lead toxicity. However, the molecular
      mechanisms by which it induces toxicity, and carcinogenesis remain to be
      elucidated. In this research, we performed the MTT assay to assess the
      cytotoxicity, and the CAT-Tox assay to assess the transcriptional responses
      associated with lead exposure to thirteen different recombinant cell lines
      generated from human liver carcinoma cells (HepG2), by creating stable
      transfectants of mammalian promoter chloramphenicol (CAT) gene fusions. Study
      results indicated that lead nitrate is cytotoxic to HepG2 cells, showing LD50
      values of 49.0 +/- 18.0 microg/mL, 37.5 +/- 9.2 microg/mL, and 3.5 +/- 0.7
      microg/mL for cell mortality upon 24, 48 and 72 h of exposure, respectively;
      indicating a dose- and time-dependent response with regard to the cytotoxic
      effect of lead nitrate. A dose-response relationship was also recorded with
      respect to the induction of stress genes in HepG2 cells exposed to lead nitrate.
      Overall, six out of the thirteen recombinant cell lines tested showed inductions
      to statistically significant levels (p < 0.05). At 50 microg/mL of lead nitrate,
      the average fold inductions were: 2.1 +/- 1.0, 5.4 +/- 0.4, 12.1 +/- 6.2, 5.0 +/-
      1.7, 2.5 +/- 1.3, and 4.8 +/- 4.5 for XRE, HSP70, CRE, GADD153, and GRP78,
      respectively. These results indicate the potential for lead nitrate to undergo
      biotransformation in the liver (XRE), to cause cell proliferation (c-fos),
      protein damage (HSP70, GRP78), metabolic perturbation (CRE), and growth arrest
      and DNA damage (GADD153). Marginal but not significant inductions were also
      obtained with the GSTYa (1.5 +/- 0.8), and GADD45 (5.7 +/- 8.1) promoters, and
      the NF-KB (2.0 +/- 1.7) response element, indicating the potential for oxidative
      stress. No significant inductions (p > 0.05) were recorded for CYP1A1, HMTIIA,
      p53RE, and RARE.

PMID- 14971658
TI  - PbCrO4 mediates cellular responses via reactive oxygen species.
AB  - Exposure to certain particulate hexavalent chromium [Cr(VI)] compounds, such as
      lead chromate (PbCrO4), has been associated with lung cancer and respiratory
      tract toxicity. Previous studies indicate that the solubility of Cr(VI)-compounds
      is an important factor in Cr(VI)-induced carcinogenesis. The present study
      investigates reactive oxygen species (ROS) generation by PbCrO4 particles and
      cellular responses using RAW 264.7 cells. A mixture containing PbCrO4 and RAW
      264.7 cells generated hydroxyl radical ((.)OH), using cellularly generated H2O2
      as a precursor, as measured by electron spin resonance (ESR) spin trapping in
      combination with H2O2 and (.)OH scavengers, catalase and sodium formate. The
      effect of ascorbic acid on (.)OH radicals was also measured using ESR. Confocal
      microscopy showed that particles could become either bound to the cell surface or
      engulfed over a 120 min time period. H2O2 generation and O2 consumption were also
      increased after treatment of the cells with PbCrO4. Both NF-kappaB and AP-1 were
      activated after exposure to PbCrO4 particles as measured by the NF-kappaB or AP-1
      luciferase reporter plasmid assay. Our investigation thus demonstrated that the
      RAW 264.7 cells phagocytized the PbCrO4 particles leading to accumulation of the
      particles within vacuoles in the cytoplasm. These particles could induce chronic
      production of ROS and activation of NF-kappaB and AP-1. Such induction of
      transcription pathways may be involved in the inflammatory and carcinogenic
      responses induced by Cr(VI)-containing particles.

PMID- 14971659
TI  - Genetic and cellular mechanisms in chromium and nickel carcinogenesis considering
      epidemiologic findings.
AB  - Genetic and environmental interactions determine cancer risks but some cancer
      incidence is primarily a result of inherited genetic deficits alone. Most cancers
      have an occupational, viral, nutritional, behavioral or iatrogenic etiology.
      Cancer can sometimes be controlled through broad public health interventions
      including industrial hygiene and engineering controls. Chromium and nickel are
      two human carcinogens associated with industrial exposures where public health
      measures apparently work. Carcinogenic mechanisms of these metals are examined by
      electron-spin-resonance-spectroscopy and somatic-mutation-and-recombination in
      Drosophila melanogaster in this report. Both metals primarily affect initiation
      processes in cancer development suggesting important theoretical approaches to
      prevention and followup.

PMID- 14971660
TI  - Reduced Fhit protein expression in nickel-transformed mouse cells and in nickel
      induced murine sarcomas.
AB  - Nickel compounds are carcinogenic and induce malignant transformation of cultured
      cells. Since nickel has low mutagenic potential, it may act predominantly through
      epigenetic mechanisms, including down-regulation of tumor suppressor genes. FHIT
      is a tumor suppressor gene whose expression is frequently reduced or lost in
      tumors and pre-malignant lesions. Previously, we have shown that the
      phosphohydrolase activity of Fhit protein, associated with its tumor suppressor
      action, is inhibited by nickel. In cells, such effect would assist in
      carcinogenesis. The latter could be further enhanced if nickel also lowered
      cellular levels of Fhit protein itself, e.g. by down-regulation of FHIT gene. To
      test this possibility, we determined Fhit protein and Fhit-mRNA levels in a
      nickel-transformed mouse cell line and in nickel-induced murine sarcomas. In B200
      cells, derived by nickel treatment of BALB/c-3T3 cells and exhibiting a malignant
      phenotype, Fhit protein levels were 50% of those in the parental cells, while
      Fhit-mRNA expression remained unchanged. A decrease of up to > 90% in Fhit
      protein levels was also observed in 22 local sarcomas (mostly fibrosarcomas)
      induced by i.m. injection of nickel subsulfide in C57BL/6 and MT+ (C57BL/6
      overexpressing metallothionein) mice, as compared with normal muscles. Moreover,
      Fhit was absent in 3 out of 10 sarcomas from MT+ mice and in 1 of 12 sarcomas
      from C57BL/6 mice. The lack of Fhit protein coincided with the absence of the
      Fhit-mRNA transcript in these tumors. However, in the other tumors, the decreased
      Fhit levels were not always accompanied by reduced expression of Fhit-mRNA. Thus,
      the observed lowering of Fhit protein levels is mostly associated with changes in
      mRNA expression and protein translation or turnover rates, and rarely with a full
      silencing of the gene itself. Overall, the decline of Fhit in cells or tissues
      malignantly transformed by nickel may indicate possible involvement of this
      effect in the mechanisms of nickel carcinogenesis.

PMID- 14971661
TI  - Molecular biology of nickel carcinogenesis: identification of differentially
      expressed genes in morphologically transformed C3H10T1/2 Cl 8 mouse embryo
      fibroblast cell lines induced by specific insoluble nickel compounds.
AB  - Inhalation of mixtures of insoluble and soluble nickel compounds by humans during
      nickel refining has been associated with excess lung and nasal sinus cancers.
      Insoluble nickel subsulfide (Ni3S2) and nickel oxide (NiO) are carcinogenic to
      rodents by inhalation. We previously showed that insoluble Ni3S2, crystalline
      nickel monosulfide (NiS), and green (high temperature, HT) and black (low
      temperature, LT) NiO, induced morphological transformation in cultured C3H/10T1/2
      Cl 8 (10T1/2) mouse embryo cells. To understand molecular mechanisms of
      carcinogenesis by insoluble nickel compounds, we used random, arbitrarily primed
      polymerase chain reaction (RAP-PCR) mRNA differential display and identified nine
      cDNA fragments that were differentially expressed between nontransformed and
      nickel-transformed cell lines in approximately 10.0% of the total mRNA.
      Expression of the calnexin gene (encoding a type I membrane protein/molecular
      chaperone), the ect-2 proto-oncogene, and the stress-inducible gene, Wdr1, was
      upregulated. Expression of six genes--the vitamin D interacting protein/thyroid
      hormone activating protein 80 (DRIP/TRAP-80) gene, the insulin-like growth factor
      receptor 1 (IGFR1) gene, the small nuclear activating protein (SNAP C3) gene, and
      three unknown genes, was down-regulated, in nickel-transformed cell lines. We
      hypothesize that these resulting aberrations in gene expression could contribute
      to the induction and/or maintenance of morphological transformation induced by
      specific insoluble nickel compounds.

PMID- 14971662
TI  - Activation of aPKC is required for vanadate-induced phosphorylation of protein
      kinase B (Akt), but not p70S6k in mouse epidermal JB6 cells.
AB  - Vanadium is a metal widely distributed in the environment. Although vanadate
      containing compounds exert potent toxic effects on a wide variety of biological
      systems, the mechanisms by which vanadate mediates adverse effects are not well
      understood. The present study investigated the vanadate-induced phosphorylation
      of Akt and p70S6K, two kinases known to be vital for cell survival, growth,
      transformation, and transition of the cell cycle in mammals. Exposure of mouse
      epidermal JB6 cells to vanadium led to phosphorylation of Akt and p70S6K in a
      time- and dose-dependent manner. Vanadium exposure also caused translocation of
      atypical isoforms of PKC (lambda, zeta) from the cytosol to the membrane, but had
      no effect on PKCalpha translocation, suggesting that the atypical PKCs (aPKC)
      were specifically involved in vanadium-induced cellular response. Importantly,
      overexpression of a dominant negative mutant PKClambda blocked Akt
      phosphorylation at Ser473 and Thr308, whereas it did not inhibit p70S6k
      phosphorylation at Thr389 and Thr421/Ser424, suggesting that aPKC activation is
      specifically involved in vanadium-induced activation of Akt, but not in
      activation of p70S6k. Furthermore, vanadium-induced p70S6k phosphorylation at
      Thr389 and Thr421/Ser424 and Akt phosphorylation at Thr308 occurred through a PI
      3K-dependent pathway because a PI-3K dominant negative mutant inhibited induction
      as compared with vector control cells. These results indicate that there was a
      differential role of aPKC in vanadate-induced phosphorylation of Akt and p70S6k,
      suggesting that signal transduction pathways leading to the activation of Akt and
      p70S6k were different.

PMID- 14971663
TI  - Vanadate activated Akt and promoted S phase entry.
AB  - Protein kinase B (PKB)/Akt and its upstream signal transducer,
      phosphatidylinosito-3 kinase (PI3K) play an essential role in control of
      transcription and translation, which impact cell growth, survival, and
      metabolism. Transcription factor E2F is a component of the downstream
      proliferative machinery regulated by Akt. Hyperphosphorylation of retinoblastoma
      protein (pRb), a pocket protein, leads to release of E2F1, resulting in
      transition from G1 to S phase. The present study shows that in normal C141 cells,
      vanadate treatment increased the percentage of cells at S phase and elevated
      cyclin E and cyclin A expression. Vanadate treatment triggered phosphorylation of
      pRb and release of E2F1. Furthermore, vanadate increased Akt kinase activity and
      caused its phosphorylation at Ser473 and Thr308. Inhibition of Akt by either
      inhibitors or transfected cells with dominant negative kinase mutant or dominant
      negative phosphorylation mutant decreased the percentage of the cells at the S
      phase induced by vanadate, and reduced both cyclin E and E2F1 expression and
      phosphorylation of pRb. The present study indicates that Akt plays an essential
      role in vanadate-induced increase in cell number at S phase and transition from
      G1 to S phase through E2F-pRb pathway.

PMID- 14971664
TI  - The role of phosphatidylinositol-3 kinase in vanadate-promoted S phase entry.
AB  - Phosphatidylinositil-3 kinase (PI3K) is a heterodimer of catalytic and regulatory
      subunits. It is involved in various signaling pathways and key functions of the
      cells. The present study investigated the role of PI3K in vanadate-induced
      alteration in cell cycle regulation in C141 mouse epidermal cells. Vanadate
      caused a time- and dose-dependent increase in PI3K activity and phosphorylation
      of p70 S6 kinase (p70S6K) at Thr421/Ser424 and Thr389 sites. The phosphorylation
      at these sites was inhibited by PI3K inhibitor, LY294002, and p70S6K mutation.
      Vanadate promoted S phase entry and this promotion was inhibited by LY294002 and
      rapmycin, a p70S6K inhibitor. Vanadate-induced enhancement in S phase entry was
      also inhibited in transfection with dominant negative p70S6K mutant cells. The
      results obtained show that vanadate is able to increase PI3K activity through
      phosphorylation. PI3K activated p70S6K, which phosphated protein S6, and promoted
      S phase entry.

PMID- 14971665
TI  - Effect of the militarily-relevant heavy metals, depleted uranium and heavy metal
      tungsten-alloy on gene expression in human liver carcinoma cells (HepG2).
AB  - Depleted uranium (DU) and heavy-metal tungsten alloys (HMTAs) are dense heavy
      metals used primarily in military applications. Chemically similar to natural
      uranium, but depleted of the higher activity 235U and 234U isotopes, DU is a low
      specific activity, high-density heavy metal. In contrast, the non-radioactive
      HMTAs are composed of a mixture of tungsten (91-93%), nickel (3-5%), and cobalt
      (2-4%) particles. The use of DU and HMTAs in military munitions could result in
      their internalization in humans. Limited data exist however, regarding the long
      term health effects of internalized DU and HMTAs in humans. Both DU and HMTAs
      possess a tumorigenic transforming potential and are genotoxic and mutagenic in
      vitro. Using insoluble DU-UO2 and a reconstituted mixture of tungsten, nickel,
      cobalt (rWNiCo), we tested their ability to induce stress genes in thirteen
      different recombinant cell lines generated from human liver carcinoma cells
      (HepG2). The commercially available CAT-Tox (L) cellular assay consists of a
      panel of cell lines stably transfected with reporter genes consisting of a coding
      sequence for chloramphenicol acetyl transferase (CAT) under transcriptional
      control by mammalian stress gene regulatory sequences. DU, (5-50 microg/ml)
      produced a complex profile of activity demonstrating significant dose-dependent
      induction of the hMTIIA FOS, p53RE, Gadd153, Gadd45, NFkappaBRE, CRE, HSP70,
      RARE, and GRP78 promoters. The rWNiCo mixture (5-50 microg/ml) showed dose
      related induction of the GSTYA, hMTIIA, p53RE, FOS, NFkappaBRE, HSP70, and CRE
      promoters. An examination of the pure metals, tungsten (W), nickel (Ni), and
      cobalt (Co), comprising the rWNiCo mixture, demonstrated that each metal
      exhibited a similar pattern of gene induction, but at a significantly decreased
      magnitude than that of the rWNiCo mixture. These data showed a synergistic
      activation of gene expression by the metals in the rWNiCo mixture. Our data show
      for the first time that DU and rWNiCo can activate gene expression through
      several signal transduction pathways that may be involved in the toxicity and
      tumorigenicity of both DU and HMTAs.

PMID- 14971666
TI  - Metal composition and solubility determine lung toxicity induced by residual oil
      fly ash collected from different sites within a power plant.
AB  - Residual oil fly ash (ROFA) is a particulate pollutant comprised of soluble and
      insoluble metals and is produced by the combustion of fossil fuels. The objective
      was to examine the pulmonary responses to chemically distinct ROFA samples
      collected from either a precipitator or air heater within the same power plant.
      The collected ROFA samples were suspended in saline (total sample), incubated for
      24 h at 37 degrees C, centrifuged, separated into soluble and insoluble
      fractions, and the metal composition was determined. In addition, electron spin
      resonance (ESR) was used to detect short-lived free radical intermediates
      produced by the ROFA samples and the different fractions. On day 0, Male Sprague
      Dawley rats were intratracheally instilled with saline (vehicle control) or the
      ROFA samples (1 mg/100 g body wt). At day 1, bronchoalveolar lavage was
      performed, and lung inflammation was assessed. On day 3, additional rats that had
      been treated with ROFA were intratracheally inoculated with 5 x 10(5) Listeria
      monocytogenes, and pulmonary bacterial clearance was measured at days 6, 8, and
      10. The precipitator ROFA was found to be more soluble and acidic with a
      significantly greater mass of each metal compared with the air heater ROFA. A
      prominent hydroxyl radical signal was measured for the total and soluble
      precipitator ROFA after the addition of H2O2, whereas the air heater ROFA and its
      fractions did not produce a signal. Precipitator ROFA induced a greater
      inflammatory response than air heater ROFA illustrated by a significant elevation
      in lung neutrophils. In addition, pulmonary clearance of L. monocytogenes was
      greatly diminished in the rats treated with the soluble and total precipitator
      ROFA samples. None of the air heater ROFA samples had an effect on lung bacterial
      clearance. In conclusion, precipitator ROFA, particularly the soluble fraction,
      generated a metal-dependent hydroxyl radical as measured by ESR and was shown to
      cause more inflammation and result in reduced lung defense against infection
      compared with air heater ROFA. These results are most likely due to differences
      in metal composition and solubility of the ROFA samples.

PMID- 14971667
TI  - Restoration of arthritic cartilage defects using autologous chondrocytes
      transplantation is superior to cartilage-paste graft in rabbits.
AB  - This study compared the articular cartilage repair potential of cultured
      chondrocytes transplantation with bone-cartilage paste-graft in the resurfacing
      of full-thickness defects without breaching of the subchondral bone plate in
      rabbit knees. A 5 x 5-mm articular cartilage defect was created in the patellar
      groove of the femur. Three months following creation, the defect was filled with
      cultured autologous chondrocytes (group 1) or bone-cartilage paste (group 2). A
      control group of untreated defects was followed for 1 year. The reparative tissue
      was analyzed macroscopically, histologically, and by immunohistochemistry 3-12
      months post-transplantation. The surfaces of the reparative tissue in group 1
      were smooth, and the defects were filled with reparative tissue that resembled
      hyaline cartilage. The composition of the repair tissue more closely resembled
      cartilage, as demonstrated by cartilage-specific stains. In contrast, the
      reparative tissue in group 2 was fibrous and exhibited markers of mesenchymal
      stem cells and bone formation. Transplantation of cultured chondrocytes into a
      full-thickness defect in the rabbit generates a biologic substitute tissue that
      resembles native articular cartilage with living cells capable of synthesizing
      the surrounding cartilage matrix. In contrast, analysis of the healing response
      to the paste-graft technique failed to show cartilage-like characteristics. This
      information may be clinically applicable to direct the use of these treatments in
      chondral injuries.

PMID- 14971668
TI  - Patient satisfaction and outcome after microfracture of the degenerative knee.
AB  - Satisfaction and functional outcome was measured in 81 patients who were treated
      arthroscopically with microfracture for isolated degenerative lesions of the
      knee. Average patient age was 49 years (range: 40-70 years) and average
      degenerative lesion measured 229.5 mm2 (range: 25-2000 mm2). Patients were
      evaluated at average 2.6-year follow-up (range: 2-5 years). All subjective
      parameters measured (pain, swelling, limping, walking, stairs, sport level, and
      activities of daily living) demonstrated significant improvement over
      preoperative status (P<.003). Lysholm score improved from 53.8 to 83.1 (P<.001),
      and mean Tegner Activity Scale score improved from 2.9 to 4.5 (P<.05). No
      significant association was noted between Lysholm improvement and gender or age.
      Significant improvement in mean Lysholm score was noted for lesions in all three
      knee compartments. Thirteen patients required repeat arthroscopy within 5 years
      of initial microfracture for lysis of adhesions. Five patients required revision
      microfracture to a previously treated lesion or total knee arthroplasty at an
      average of 23 months (range: 5-36 months) from the initial microfracture.
      Microfracture is an efficacious surgical option for the treatment of degenerative
      chondral lesions of the knee. The modest rate of failure and need for
      arthroscopic lysis of adhesions reflects the challenge of joint-sparing
      arthroscopic surgery in the degenerative knee.

PMID- 14971669
TI  - Postoperative pain management after anterior cruciate ligament reconstruction.
AB  - This study compared pain and its management in four groups of patients after
      anterior cruciate ligament (ACL) surgery. Group 1 consisted of primary ACL
      reconstruction, group 2 primary ACL reconstruction with meniscal repair, group 3
      primary ACL reconstruction with meniscal resection, and group 4 revision ACL
      reconstruction with patellar tendon allograft. Each patient was instructed to
      record his or her pain level on a visual analog pain scale (VAS) prior to the
      procedure and for 7 days postoperatively. All patients received a prescribed
      narcotic to be taken orally as needed every 4-6 hours. Each patient was
      instructed to taper its use and supplement with non-narcotic as symptoms allowed.
      The VAS score for all groups peaked at postoperative day 1 and remained elevated
      at postoperative day 2. At postoperative day 7, the VAS scores for groups 1, 2,
      and 3 began to show signs of further decline, whereas group 4 persisted at
      postoperative day 5 levels. A general trend of decreasing narcotic use over time
      and increasing non-narcotic use was noted in each group; however, these findings
      were not statistically significant. All four groups had nearly identical mean VAS
      scores and corresponding narcotic use for each postoperative day despite the
      differing levels of complexity of surgical intervention in each group.

PMID- 14971670
TI  - The role of drains and tourniquets in primary total knee replacement: a
      comparative study of TKR performed with drains and tourniquet versus no drains
      and adrenaline and saline infiltration.
AB  - One hundred fifteen consecutive patients undergoing TKR were divided into two
      groups to determine whether blood loss and transfusion in total knee replacement
      (TKR) using adrenaline with saline infiltration would be less than TKR with
      tourniquet and drain. Group 1, composed of 60 patients, received 2.5 mg of 1:1000
      adrenaline diluted in 500 mL of normal saline, which was infiltrated into the
      skin, subcutaneous tissues, and capsule before surgical incision. No tourniquets
      or postoperative drains were used. Group 2, composed of 55 patients, had a
      tourniquet and postoperative drain. Thromboprophylaxis with low molecular weight
      heparin also was used. Pre- and postoperative hemoglobin, blood loss, hematocrit,
      and transfusion requirements were studied in both groups; in group 2, blood loss
      in the drains also was noted. Average preoperative hemoglobin and hematocrit in
      the two groups were 13.7 g/dL and 39.3 g/dL, respectively, and 13.5% and 39%,
      respectively. Average intraoperative blood loss was 290 mL in group 1 and 377.7
      mL in group 2 (P<.005). Postoperative blood loss in group 1 was <50 mL based on
      dressing soakage and 297.7 mL in group 2 (P<.005). Average postoperative
      hemoglobin and hematocrit in the two groups were 10.6 g/dL and 8.4 g/dL,
      respectively, and 35.4% and 31.1%, respectively. Transfusion rates were 3.3% and
      23.6%, respectively (P<.005). The average volume transfused was 1.2 U. Adrenaline
      and saline infiltration is safe and helps reduce intraoperative blood loss.
      Suction drain use for surgical wounds after primary, uncomplicated TKR is
      questionable.

PMID- 14971671
TI  - Giant-cell tumor of the tendon sheath arising from the patellar tendon.

PMID- 14971672
TI  - Osteoarthritic cyst mimicking patellar osteonecrosis.

PMID- 14971673
TI  - The biomechanics of patellofemoral stability.

PMID- 14971674
TI  - Injured medial patellofemoral ligament in acute patellar dislocation.

PMID- 14971675
TI  - Indications in the treatment of patellar instability.
AB  - Recent developments in patellar instability have focused on the passive
      restraints against mediolateral patellar motion. Viewed from this perspective,
      muscle alignment is considered secondary because, although muscle forces are
      important, their ability to cause or prevent patellar dislocation depends on
      passive stability or the lack thereof. In the normal knee, the patella seats
      quickly in the trochlea in early flexion, so that the ligamentous restraints are
      important only near full extension. In the unstable patellofemoral joint, the
      trochlea frequently is deficient and patella alta often exists. In such cases,
      the ligaments assume a greater role in preventing excessive lateral patellar
      displacement. The most pressing questions at the moment are: 1) which of the
      anatomical abnormalities must be corrected, alone or in combination, to prevent
      further patellar instability; and 2) what is the relative risk of corrective
      procedures compared to the natural history or competing surgical approaches?
      These questions must be addressed by clinical trials. Only a minority of patients
      who experience patellar dislocation will redislocate the patella, and surgical
      treatment does not always yield results that are superior to conservative care.
      Treatment recommendations should be based on an individual's risk of recurrent
      dislocation, pain, and disability, a thorough understanding of his or her
      anatomy, and clear treatment objectives. Lateral release has no role in the
      treatment of a hyperlax patellofemoral joint, as it adds additional laxity to a
      system that is already unstable. If surgery is performed, current evidence
      suggests techniques aimed at repair or reconstruction of the passive retinacular
      restraints are as effective as more extensive procedures at preventing subsequent
      dislocations. Among the latter procedures, realignment procedures use active
      muscle forces to help seat the patella in the femoral groove; however,
      biomechanical costs are associated with this approach and superior results have
      not been demonstrated with distal and combined realignments compared with more
      limited proximal procedures.

PMID- 14971676
TI  - Crop protection--what will shape the future picture?
AB  - The drivers which influence the types of crop protection most needed by
      agriculture are changing. A polarisation of approaches has resulted in the needs
      of organic agriculture and biotechnological agriculture, which can be identified
      as the current extremes of the spectrum, becoming very different. The main
      requirements of these two sectors are identified here and used as the basis for
      questioning future EU research requirements in crop protection. Factors
      affecting/influencing organic farming and the use of genetically modified crops
      are discussed in some detail.

PMID- 14971677
TI  - Occurrence of barley yellow dwarf virus in autumn-sown cereal crops in the United
      Kingdom in relation to field characteristics.
AB  - The incidence of barley yellow dwarf virus and of its aphid vectors was surveyed
      in untreated parts of autumn-sown cereal crops, mainly wheat and barley, in the
      United Kingdom in 1995-8. The incidence of virus in the spring was related to the
      incidence of aphids in the preceding autumn. Both virus and aphid incidences
      could also be related to a range of crop and field characteristics, in particular
      sowing date, regions as defined by their geographical position, topography and
      climate, the proximity of the field to the sea, the extent of arable land in the
      vicinity of the field, and the aspect and size of the field. Proximity of cropped
      fields to setaside areas had no significant effect on either aphid or virus
      incidence.

PMID- 14971678
TI  - Potassium phosphate induces systemic protection in barley to powdery mildew
      infection.
AB  - In laboratory tests, treatment of the first leaves of barley (Hordeum vulgare L
      cv Golden Promise) with potassium phosphate led to significant reduction in
      infection of the second leaves with the powdery mildew fungus Blumeria graminis f
      sp hordei Marchal, with a 25 mM treatment giving 89% reduction in infection.
      Although the optimal interval between phosphate treatment of the first leaves and
      mildew inoculation of the second leaves was 2 days, significant protection was
      still obtained if the interval was increased to 12 days. Protection against
      powdery mildew infection was not as effective when the potassium phosphate was
      applied as a seed treatment or root drench. Phosphate treatment of the first
      leaves led to significant increases in activities of phenylalanine ammonia lyase
      (PAL), peroxidase and lipoxygenase in second leaves. Enzyme activities,
      especially PAL and peroxidase, were increased further when second leaves of
      phosphate-treated plants were inoculated with powdery mildew. Phosphate treatment
      of the first leaves did not adversely affect plant growth and, in a field trial,
      25 mM potassium phosphate provided 70% control of mildew and gave a small
      increase in grain yield.

PMID- 14971679
TI  - Biology and integrated control of Pestalotiopsis on container-grown ericaceous
      crops.
AB  - Pestalotiopsis isolates obtained from the foliage, stem-base and roots of
      diseased container-grown ericaceous crops (Calluna, Erica, Pieris and
      Rhododendron) collected from UK nurseries were identified as Pestalotiopsis
      sydowiana (Bresad) B Sutton on the basis of conidia morphology. Inoculum sources
      of the pathogen included diseased stock plants, crop debris, nursery soils, used
      growing media, pots and floor covering, and dust collected from greenhouse
      walkways. Isolates were not host-specific and infected other species of
      ericaceous plants, with typical symptoms including browning of foliage, stems and
      roots, and the presence of black or greenish black acervuli on diseased tissue.
      The optimum temperature for growth of three selected isolates of the pathogen was
      20-25 degrees C, with little or no growth occurring below 5 or above 30 degrees
      C. Growth occurred over pH 2.6-8.6, with optimum at 5.5. Decreases in matric
      potential from -0.3 to -4.0 MPa reduced growth, which was totally inhibited at 
      6.5 MPa. Greenhouse trials were conducted to evaluate the effects of disease
      management methods (irrigation, flooring/pot disinfection and fungicide
      application) on control of the pathogen on potted plants of C vulgaris. Disease
      incidence and foliar browning caused by P sydowiana were less on fungicide
      treated (five-spray programme of alternating prochloraz and carbendazim) potted
      plants watered by sub-irrigation compared with watering from overhead. Single and
      combined treatments of flooring/pot disinfection (hydrogen peroxide/peracetic
      acid) and the five-spray fungicide programme significantly reduced disease
      incidence and severity compared with dipping pots in water. The combined
      disinfection and fungicide programme significantly reduced disease incidence and
      severity, compared to disinfection or fungicide application alone. The importance
      of these findings for the integrated control of P sydowiana on ericaceous plant
      nurseries is discussed.

PMID- 14971680
TI  - Synthesis and antifungal activity of five classes of diamines.
AB  - Examples of five classes of diamines were synthesized and tested for antifungal
      activity. Two classes, the bis(cyclohexylmethyl)diamines and the
      bis(benzyl)diamines, were most effective in reducing mycelial growth of the oat
      leaf stripe pathogen Pyrenophora avenae Ito & Kuribay when used at a
      concentration of 250microM. The bis(benzyl)diamine BBD5 and the
      hydroxypyridylethylamine HPE2 both reduced powdery mildew infection of barley
      seedlings by greater than 70% when applied as a post-inoculation spray at 250
      microM. Several of the compounds examined, and especially BBD5 and HPE2, reduced
      the formation of spermidine but greatly increased spermine levels. These changes
      in P avenae treated with BBD5 and HPE2 were also accompanied by greatly elevated
      activity of polyamine oxidase. It is suggested that the antifungal activity of
      these compounds may be related to the accumulation of spermine and specifically
      to its toxicity.

PMID- 14971681
TI  - The potential role of arbuscular mycorrhizal (AM) fungi in the bioprotection of
      plants against soil-borne pathogens in organic and/or other sustainable farming
      systems.
AB  - Sustainable farming systems strive to minimise the use of synthetic pesticides
      and to optimise the use of alternative management strategies to control soil
      borne pathogens. Arbuscular mycorrhizal (AM) fungi are ubiquitous in nature and
      constitute an integral component of terrestrial ecosystems, forming symbiotic
      associations with plant root systems of over 80% of all terrestrial plant
      species, including many agronomically important species. AM fungi are
      particularly important in organic and/or sustainable farming systems that rely on
      biological processes rather than agrochemicals to control plant diseases. Of
      particular importance is the bioprotection conferred to plants against many soil
      borne pathogens such as species of Aphanomyces, Cylindrocladium, Fusarium,
      Macrophomina, Phytophthora, Pythium, Rhizoctonia, Sclerotinium, Verticillium and
      Thielaviopsis and various nematodes by AM fungal colonisation of the plant root.
      However, the exact mechanisms by which AM fungal colonisation confers the
      protective effect are not completely understood, but a greater understanding of
      these beneficial interactions is necessary for the exploitation of AM fungi
      within organic and/or sustainable farming systems. In this review, we aim to
      discuss the potential mechanisms by which AM fungi may contribute to
      bioprotection against plant soil-borne pathogens. Bioprotection within AM fungal
      colonised plants is the outcome of complex interactions between plants, pathogens
      and AM fungi. The use of molecular tools in the study of these multifaceted
      interactions may aid the optimisation of the bioprotective responses and their
      utility within sustainable farming systems.

PMID- 14971682
TI  - Climate change and decreasing herbicide persistence.
AB  - A herbicide degradation model, using real weather data for the period 1980-2001,
      has been used to estimate the change in persistence of autumn-applied isoproturon
      over this period. The results suggest that soil residues fell to the minimum for
      weed control on average approximately 30 days earlier over the last 5 years of
      this period than in the first 5 years, equivalent to a reduction of approximately
      25% in the duration of weed control. This decline in persistence is attributed to
      increasing soil temperature. The results are discussed in relation to recent
      observations and predictions on climate change. The relevance of the findings to
      other pesticides and future weed control is considered.

PMID- 14971683
TI  - Monitoring glyphosate residues in transgenic glyphosate-resistant soybean.
AB  - The availability of Roundup Ready (RR) varieties of soybean has increased the use
      of glyphosate for weed control in Argentina. Glyphosate [(N
      phosphonomethyl)glycine] is employed for the eradication of previous crop
      vegetation and for weed control during the soybean growing cycle. Its action is
      effective, and low environmental impact has been reported so far. No residues
      have been observed in soil or water, either of glyphosate or its metabolite, AMPA
      (aminomethylphosphonic acid). The objective of this work was to monitor
      glyphosate and AMPA residues in soybean plants and grains in field crops in Santa
      Fe Province, Argentina. Five sites were monitored in 1997, 1998 and 1999.
      Individual soybean plants were sampled from emergence to harvest, dried and
      ground. Analysis consisted in residue extraction with organic solvents and
      buffers, agitation, centrifugation, clean-up and HPLC with UV detection. In
      soybean leaves and stems, glyphosate residues ranged from 1.9 to 4.4 mg kg(-1)
      and from 0.1 to 1.8 mg kg(-1) in grains. Higher concentrations were detected when
      glyphosate was sprayed several times during the crop cycle, and when treatments
      approached the flowering stage. AMPA residues were also detected in leaves and in
      grains, indicating metabolism of the herbicide.

PMID- 14971684
TI  - Long-term selection for resistance to transgenic cotton expressing Bacillus
      thuringiensis toxin in Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae).
AB  - Selection experiments for resistance to transgenic Bt cotton expressing Cry1Ac
      toxin in Helicoverpa armigera (Hubner) were conducted using a leaf-feeding method
      with 42 selection episodes over 45 generations. The cotton bollworm developed
      resistance to transgenic Bt cotton after 12 generations (F12) of selection. The
      survival rate of F12 neonates feeding on leaves of seedling stage for 4 days and
      boll-opening stage for 5 days of R19 line were ca 34 and 72%, respectively,
      compared with ca 0 and 40% for a non-selected sister strain (NYCS), but lower
      than or similar to that of F12 feeding on leaves of non-Bt cotton, Sumian 12 (ca
      87 or 76%). Resistance to B thuringiensis HD-1 Dipel in neonates (F12) was ca 6
      fold. After 42 generations of selection, the strain developed a very high level
      of resistance to Cry1Ac protoxin, 210 g kg(-1) MVPII wettable powder and 200 g
      litre(-1) MVPII liquid formulation, the resistance ratios being 1680-, 1780- and
      ca 1200-fold, respectively, compared with a laboratory susceptible strain (HZS).
      When compared with the non-selected NYCS, the resistance ratios to the above
      toxins were ca 540-, 580- and 510-fold, respectively, but to Dipel only ca 16
      fold. The results indicated that it is very important to develop and implement
      effective resistance-management strategies and to detect early resistance to Bt
      cotton in field populations.

PMID- 14971685
TI  - Insecticidal effects of essential oils from various plants against larvae of pine
      processionary moth (Thaumetopoea pityocampa Schiff) (Lepidoptera:
      Thaumetopoeidae).
AB  - Along with sulfate turpentine, the essential oils obtained by steam distillation
      from nine plant species naturally grown in Turkish forests were tested at three
      different concentrations to evaluate their effectiveness against the larvae of
      pine processionary moth (Thaumetopoea pityocampa Schiff). The results indicated
      that the essential oils from the nine species and sulfate turpentine were
      effective against the larvae of T pityocampa. The most effective essential oil in
      the control of the larvae was steam-distilled wood turpentine, followed by thyme
      herb oil, juniper berry oil, laurel leaf oil, lavender flower oil, eucalyptus
      leaf oil, lavender leaf oil, cypress berry oil, essential oil of styrax and
      sulfate turpentine, respectively, in terms of mean mortality time. It is
      therefore feasible to use these essential oils as environment-friendly
      insecticides in the control of T pityocampa.

PMID- 14971686
TI  - Molluscicidal effects of neem (Azadirachta indica) extracts on edible tropical
      land snails.
AB  - The effects of 350, 500 and 700 mg kg(-1) of crude extracts of neem, Azadirachta
      indica A Juss, on edible tropical land snails Archachatina marginata and
      Limicolaria aurora (Jay) were determined and compared with control using pawpaw,
      Carica papaya L as bait. Responses were measured through normal feeding,
      cessation of food intake, cessation of crawling, mucus secretion, lack of
      response to mechanical stimuli (mortality) and decomposition. Results showed no
      effects on the controls or snails exposed to neem seed oil extract. Crude
      extracts of bark, root and leaf of neem at 500 and 700 mg kg(-1) produced
      mortality after exposure for 48 h for L aurora and 72 h for A marginata.

PMID- 14971687
TI  - Benzoylphenylurea residues in peppers and zucchinis grown in greenhouses:
      determination of decline times and pre-harvest intervals by modelling.
AB  - Residue levels and degradation rates of five benzoylphenylurea insecticides were
      studied in zucchinis and peppers grown in experimental greenhouses in Almeria
      (Spain). Benzoylphenylurea residues were analyzed by HPLC using on-line post
      elution photoirradiation with fluorescence detection. Mathematically defined
      decline curves were established by determining optimal relationships between
      benzoylphenylurea residues and time, using different models. The models that best
      fitted the experimental data were those of first-order for diflubenzuron,
      triflumuron, hexaflumuron and flufenoxuron in zucchini and RF first-order models
      for the five insecticides in peppers and for lufenuron in zucchini. Half-life
      times for the residues on the two vegetables were estimated from the optimal
      models. In order to guarantee safe consumption of the two vegetables, we have
      estimated suitable pre-harvest intervals complying with the maximum residue
      levels established by the Spanish Government. In all cases, such pre-harvest
      intervals were shorter than those specified by the manufacturers of commercial
      formulates. Experimental data for the five insecticides in peppers and for
      lufenuron in zucchini were also fitted to a first-order model. Even though this
      function was legitimized statistically, estimations of decline times (T/2) and
      pre-harvest intervals were quite different from those provided by the optimal
      model.

PMID- 14971688
TI  - Responses of Corcyra cephalonica (Stainton) to pirimiphos-methyl, spinosad, and
      combinations of pirimiphos-methyl and synergized pyrethrins.
AB  - Field control failures with pirimiphos-methyl against the rice moth, Corcyra
      cephalonica (Stainton), in Weslaco, Texas, USA, led us to investigate the
      susceptibility of this particular strain to pirimiphos-methyl, spinosad,
      pyrethrins synergized with piperonyl butoxide, and pirimiphos-methyl combined
      with synergized pyrethrins. In laboratory bioassays, 50 eggs of C cephalonica
      were exposed to untreated and insecticide-treated corn and sunflower seeds to
      determine larval survival after 21 days, egg-to-adult emergence after 49 days,
      and larval damage to seeds at both exposure periods. Pirimiphos-methyl at both 4
      and 8 mg kg(-1) did not prevent larval survival or egg-to-adult emergence of C
      cephalonica on either corn or sunflower seeds, and seed damage was evident at
      both rates. The C cephalonica strain was highly susceptible to spinosad at 0.5
      and 1 mg kg(-1). At both spinosad rates, reduction in larval survival, egg-to
      adult emergence, and seed damage relative to the control treatment was > or = 93%
      on both corn and sunflower seeds. Pirimiphos-methyl and spinosad were generally
      more effective against C cephalonica on corn than sunflower seeds. The C
      cephalonica strain was completely controlled on corn treated with 1.5 mg kg(-1)
      of pyrethrins synergized with 15 mg kg(-1) of piperonyl butoxide. Many larvae
      survived and became adults on corn treated with synergized pyrethrins at < or =
      0.75 mg kg(-1). Corn treated with pirimiphos-methyl at 4, 6 or 8 mg kg(-1) in
      combination with 0.38 to 1.5 mg kg(-1) of synergized pyrethrins reduced larval
      survival by > or = 95%, egg-to-adult emergence by > or = 97%, and seed damage by
      > or = 94%. Our results suggest that the C cephalonica strain can be controlled
      on corn by combining pirimiphos-methyl with synergized pyrethrins or with
      synergized pyrethrins at the labeled rate. Although spinosad is not currently
      labeled for use on stored corn and sunflower seeds, it appears to be effective
      against C cephalonica on both commodities at very low rates.

PMID- 14971689
TI  - Feeding deterrent and growth inhibitory properties of limonoids from Khaya
      senegalensis against the cotton leafworm, Spodoptera littoralis.
AB  - Three rearranged phragmalin-type limonoids, khayanolide A, khayanolide B and 1-O
      acetylkhayanolide B, and a mexicanolide-type limonoid, khayalactol, have been
      isolated from the stem bark of Khaya senegalensis (Desr) A Juss (Meliaceae). The
      antifeedant and growth-inhibitory activities of the isolated compounds were
      evaluated on Spodoptera littoralis (Boisduval). When added to an artificial diet,
      khayanolide A, khayanolide B and 1-O-acetylkhayanolide B showed antifeedant
      activity in a concentration-dependent manner. Khayalactol exhibited strong
      antifeedant activity without significant differences at all of the tested
      concentrations (7.5-100 mg kg(-1)). Khayanolide B was the most potent antifeedant
      with an ECso of 2.19 mg kg(-1). The results also revealed that the isolated
      compounds caused marked larval growth inhibition on S littoralis after 7 days of
      feeding on treated diet; this effect was concentration-dependent. Khayanolide B
      was the most active growth inhibitor among the isolated compounds, with an EC50
      of 6.96 mg kg(-1).

PMID- 14971690
TI  - The use of anti-malarial drugs to prevent malaria in the population of malaria
      endemic areas.
AB  - Anti-malarial drugs have been used in various ways to prevent malaria in the
      resident populations of endemic areas for nearly 100 years. The primary aim of
      most early studies was to interrupt transmission. This was rarely achieved, but
      administration of anti-malarial drugs either through medication of salt or by
      mass administration frequently led to a marked reduction in the prevalence of
      malaria infection and in the incidence of clinical attacks. Chemoprophylaxis is
      highly effective in reducing mortality and morbidity from malaria in young
      children and pregnant women living in endemic areas, but is difficult to sustain
      and, in some studies, has impaired the development of naturally acquired
      immunity. Intermittent preventive treatment, in which full therapeutic doses of a
      drug are given at defined intervals, has the potential to provide some of the
      benefits of sustained chemoprophylaxis in pregnant women and young children
      without some of its drawbacks and is a promising new approach to malaria control.

PMID- 14971691
TI  - Hematologic and clinical indices of malaria in a semi-immune population of
      western Thailand.
AB  - This study examines hematologic profiles of persons with acute Plasmodium
      falciparum or P. vivax infection in Maesod on Thailand's western border with
      Myanmar compared with febrile, non-parasitemic persons also reporting to malaria
      clinics. Nine hundred seventy-nine subjects were malaria-negative, 414 were
      infected with P. falciparum, and 646 were infected with P. vivax. Persons with
      patent parasitemia tended to have significantly lower white blood cell, red blood
      cell, platelet, and hemoglobin levels than those who were malaria-negative. For
      the first time, a parallel trend in thrombocytopenia with parasitemia was found
      to be associated with both P. falciparum, and P. vivax infection. Using logistic
      regression, persons with platelet counts < 150,000/microL were 12-15 times more
      likely to have malaria than persons with platelet counts > or = 150,000/microL.
      This study supplements previous literature on the hematologic effects of malaria
      and helps define those alterations for a semi-immune population. Thrombocytopenia
      is identified as a key indicator of malaria in these febrile patients.

PMID- 14971692
TI  - Introduced Plasmodium vivax malaria in a Bolivian community at an elevation of
      2,300 meters.
AB  - Tuntunani, Bolivia, a community of 199 persons situated at an elevation of 2,300
      meters, experienced its first malaria outbreak in 1998. Blood smears from 63 of
      183 symptomatic residents were examined, and 52 showed Plasmodium vivax. An
      investigation two years later indicated that the epidemic resulted from
      introduced transmission, since persons of all ages and both sexes were infected,
      and there had been no travel to low-lying endemic areas in the five months
      preceding the epidemic. Treatment became available only two months into the
      epidemic, at which time 58% of the people had been ill for three weeks or longer.
      This outbreak demonstrates the vulnerability of highland populations with poor
      access to health care to introduced malaria.

PMID- 14971693
TI  - Molecular analysis of Plasmodium falciparum recrudescent malaria infections in
      children treated with chloroquine in Nigeria.
AB  - Parasite genotyping by a polymerase chain reaction was used to distinguish
      recrudescent from newly acquired Plasmodium falciparum infections in 50 of 160
      Nigerian children taking part in a chloroquine efficacy study in Ibadan, Nigeria.
      A finger prick blood sample was taken from each child before and after treatment
      to identify recrudescent parasites. By investigating allelic variation in three
      polymorphic antigen loci, merozoite surface protein-1 (MSP-1), MSP-2, and
      glutamate-rich protein (GLURP), we determined parasite diversity in the
      population and in the infected host. DNA from pretreatment and post-treatment
      samples from 47 of the 50 patients who failed therapy was successfully amplified
      by the PCR. The MSP-1, MSP-2, and GLURP genotypes in all samples showed extensive
      diversity, indicating polyclonal infections. The average number of clones per
      infection in pre-treatment sample was 2.5 with MSP-1, 4.9 with MSP-2, and 2 with
      GLURP. The extent of multiplicity decreased significantly (P = 0.016) in
      posttreatment samples. Multiplicity of infection and initial parasite density
      were not age dependent. Comparison of the variant alleles in pretreatment and
      post-treatment samples of each patient indicates that 26 of the 47 children had
      genuinely recrudescent disease. Conversely, post-treatment samples from five
      children showed completely new genotypes, indicating either a previously
      sequestered population of parasites or a newly acquired infection. Overall, this
      study has shown the diversity and complexity of P. falciparum population in
      Ibadan, Nigeria. The study has also shown the dynamics of P. falciparum
      infections in this population before and after chloroquine treatment in an area
      of high malaria transmission.

PMID- 14971694
TI  - Differentiation of members of the Anopheles fluviatilis species complex by an
      allele-specific polymerase chain reaction based on 28S ribosomal DNA sequences.
AB  - Anopheles fluviatilis, one of the major vectors of malaria in India, is a complex
      of at least three cryptic species provisionally designated as species S, T, and
      U. Identification of the cryptic species of An. fluviatilis complex is of
      paramount importance in disease control program due to contrasting differences in
      their vectorial efficiency, preference for feeding on humans, and resting
      behavior. Species S, T, and U are morphologically indistinguishable at any stage
      of their life cycle and can be identified only by the examination of species
      specific fixed inversions in the polytene chromosomes. We report an allele
      specific polymerase chain reaction assay for the differentiation of members of
      An. fluviatilis complex, which is based on differences in nucleotide sequences in
      D3 domain of 28S ribosomal DNA. The assay was evaluated against chromosomally
      examined individuals from different localities with different sympatric
      associations and was found to differentiate unambiguously all the members of the
      complex.

PMID- 14971695
TI  - Comparative field evaluation of the Mbita trap, the Centers for Disease Control
      light trap, and the human landing catch for sampling of malaria vectors in
      western Kenya.
AB  - The mosquito sampling efficiency of a new bed net trap (the Mbita trap) was
      compared with that of the Centers for Disease Control miniature light trap (hung
      adjacent to an occupied bed net) and the human landing catch in western Kenya.
      Overall, the Mbita trap caught 48.7 +/- 4.8% (mean +/- SEM) the number of
      Anopheles gambiae Giles sensu lato caught in the human landing catch and 27.4 +/-
      8.2% of the number caught by the light trap. The corresponding figures for
      Anopheles funestus Giles were 74.6 +/- 1.3% and 39.2 +/- 1.9%, respectively.
      Despite the clear differences in the numbers of mosquitoes caught by each method,
      both the Mbita trap and light trap catches were directly proportional to human
      landing catches regardless of mosquito density. No significant differences in
      parity or sporozoite incidence were observed between mosquitoes caught by the
      three methods for either An. gambiae s.l. or An. funestus. Identification of the
      sibling species of the An. gambiae complex by a polymerase chain reaction
      indicated that the ratio of An. gambiae Giles sensu stricto to An. arabiensis
      Patton did not vary according to the sampling method used. It is concluded that
      the Mbita trap is a promising tool for sampling malaria vector populations since
      its catch can be readily converted into equivalent human biting catch, it can be
      applied more intensively, it requires neither expensive equipment nor skilled
      personnel, and it samples mosquitoes in an exposure-free manner. Such intensive
      sampling capability will allow cost-effective surveillance of malaria
      transmission at much finer spatial and temporal resolution than has been
      previously possible.

PMID- 14971696
TI  - Polymerase chain reaction monitoring of transmission of Onchocerca volvulus in
      two endemic states in Mexico.
AB  - To investigate the impact of mass ivermectin treatments in Mexico on Onchocerca
      volvulus transmission, entomologic surveys were carried out in the two endemic
      states of Oaxaca and Chiapas. The data suggest that substantial progress towards
      the goal of elimination has been made. A comparison pre- and post-ivermectin data
      from a community in Southern Chiapas showed a 97% decrease in seasonal
      transmission potential, but some level of polymerase chain reaction positivity
      was still detectable. In other communities from northern Chiapas and Oaxaca where
      there are no baseline data, there was an absence or near absence of infective
      flies. Residual transmission was not evenly distributed because differences were
      seen in the infection and infective rates from different catch points. These
      findings suggest that while substantial progress towards elimination has been
      made in Mexico, it may be necessary to modify ivermectin distribution strategies
      to eliminate transmission in areas where transmission persists.

PMID- 14971697
TI  - Funiculitis due to Schistosoma haematobium: uncommon diagnosis using
      parasitologic analysis of semen.
AB  - Schistosomal funiculitis is one of the rare localizations of longstanding chronic
      infection with schistosomiasis. We report a case of a 24-year-old-man who
      experienced iliac fossa pain and weight loss eight years after his last trip to
      Mali. Clinical diagnosis of lesions in the genitourinary tract due to
      schistosomiasis and biologic analysis are required to diagnose this uncommon
      localization of schistosomiasis.

PMID- 14971698
TI  - Factors influencing the transmission of Schistosoma japonicum in the mountains of
      Sichuan Province of China.
AB  - Twenty villages in the Anning River Valley of southwestern Sichuan China were
      surveyed for Schistosoma japonicum infections in humans and domestic animals.
      Also surveyed were human water contact patterns, snail populations, cercarial
      risk in irrigation systems, and agricultural land use. Few animals were infected,
      while village prevalence of infection in humans ranged from 3% to 68% and average
      village eggs per gram of stool ranged from 0 to 110. Except for occupation and
      education, individual characteristics were not strong determinants of infection
      intensity within a village. Differences in human infection intensity between
      these villages are strongly associated with crop type, with low-intensity
      villages principally growing rice, in contrast to villages devoting more land to
      vegetables and tobacco. Cercarial risk in village irrigation systems is
      associated with snail density and human infection intensity through the use of
      manure-based fertilizer. Some of the agricultural and environmental factors
      associated with infection risk can be quantified using remote sensing technology.

PMID- 14971699
TI  - Low heritable component of risk for infection intensity and infection-associated
      disease in urinary schistosomiasis among Wadigo village populations in Coast
      Province, Kenya.
AB  - To estimate their heritable component of risk for Schistosoma haematobium
      infection intensity and disease, we performed a community-based family study
      among an endemic population in coastal Kenya. Demography and family linkages were
      defined by house-to-house interviews, and infection prevalence and disease
      severity were assessed by standard parasitologic testing and by ultrasound. The
      total population was 4,408 among 912 households, with 241 identified pedigree
      household groups. Although age- and sex-adjusted risk for greater infection
      intensity was clustered within households (odds ratio = 2.7), analysis of
      extended pedigree-household groups indicated a relatively low heritability score
      for this trait (h2 = 0.199), particularly after adjustment for common household
      exposure effects (adjusted h2 = 0.086). Statistical evidence was slightly
      stronger (h2 = 0.353) for familial clustering of bladder morbidity, with an
      adjusted h2 = 0.142 after accounting for household exposure factors. We conclude
      that among long-established populations of coastal Kenya, heritable variation in
      host susceptibility is low, and likely plays a minimal role in determining
      individual risk for infection or disease.

PMID- 14971700
TI  - The effect of repeated half-yearly diethylcarbamazine mass treatment on
      Wuchereria bancrofti infection and transmission in two East African communities
      with different levels of endemicity.
AB  - The effect of repeated half-yearly mass treatment with diethylcarbamazine (DEC, 6
      mg/kg body weight) on infection and transmission of Wuchereria bancrofti was
      assessed and compared in communities with high and low endemicity in eastern
      Africa, with pretreatment microfilaria (mf) and circulating filarial antigen
      (CFA) prevalences of 29.4% and 53.2% in the high endemicity community and 3.1%
      and 18.7% in the low endemicity community, respectively. Human infection was
      monitored by repeated cross-sectional surveys, and transmission by weekly light
      trap collection of vector mosquitoes in selected houses in each community.
      Treatments resulted in a progressive decrease in microfilaremia and circulating
      antigenemia in both communities, with relative reductions being considerably
      higher for mf than for CFA. Among pretreatment mf-positive individuals, more than
      60% were diagnosed as mf negative and mean mf intensities were reduced by 99% in
      both communities after two treatment rounds. In contrast, only moderate
      reductions were seen in circulating antigenemia among pretreatment CFA-positive
      individuals, with mean intensities still being 24-39% of pretreatment values
      after two treatment rounds. Among the pretreatment mf/CFA-positive individuals,
      clearance to a CFA-negative status was negligible. Complete CFA clearance was
      only observed among pretreatment CFA-positive but mf negative individuals who
      also had much lower initial mean CFA levels than the mf-positive individuals.
      After treatment, the intensity of transmission decreased in the high-endemicity
      community, but this appeared mainly to be a consequence of a drought-induced
      reduction in vector density rather than to reduced mf load in the human
      population, since the proportion of mosquitoes carrying infective larvae was not
      reduced. No change in transmission or mosquito infectivity was observed after
      treatment in the low-endemicity community. Implications of these observations for
      the control of Bancroftian filariasis are discussed.

PMID- 14971701
TI  - A comparative study of the effectiveness of diagnostic tests for visceral
      leishmaniasis.
AB  - We compared the validity of pancytopenia, the formol-gel test (FGT), the indirect
      fluorescence antibody test (IFAT), the direct agglutination test (DAT), and the
      rK39 dipstick test as diagnostic criteria for visceral leishmaniasis (VL) in
      Nepal. Between September 2000 and January 2002, 310 clinical suspects had a bone
      marrow aspirate, and if negative, a spleen aspirate smear examined for Leishmania
      donovani. Sensitivity and specificity of all tests were determined compared with
      parasitology and by latent class analysis (LCA). Compared with parasitology, the
      sensitivities of the other tests were as follows: pancytopenia = 16.3% (95%
      confidence interval [CI] = 11.3-22.5%), FGT = 39.9% (95% CI = 32.7-47.4%), IFAT =
      28.4% (95% CI = 22.0-35.5%), DAT = 95.1% (95% CI = 90.8-97.7%), and the rK39
      dipstick test = 87.4% (95% CI = 81.7-91.9%). Sensitivity estimates obtained by
      LCA were similar, but specificity estimates were substantially higher (DAT =
      93.7% versus 77.8%; rK39 dipstick test = 93.1% versus 77.0%). The DAT or the rK39
      dipstick test can replace parasitology as the basis of a decision to treat VL in
      Nepalese peripheral health services.

PMID- 14971702
TI  - Direct agglutination test with urine samples for the diagnosis of visceral
      leishmaniasis.
AB  - A new direct agglutination test (DAT) for use with urine samples for the
      diagnosis of visceral leishmaniasis (VL) has been developed and compared with the
      conventional DAT with serum samples and our previously reported enzyme-linked
      immunosorbent assay (ELISA) with urine samples (urine ELISA). The new DAT, in
      which anti-human IgG was used as enhancing antibody, was tested with urine
      samples from 75 VL patients and 225 non-VL patients and healthy people. The
      sensitivity of the new DAT (90.7%), was almost the same as that of the
      conventional DAT (91.0%) and the urine ELISA (93.3%). The specificity of the new
      DAT (96.4%) was nearly identical with that of the urine ELISA (97.3%). A urine
      based DAT has several advantages over the conventional DAT: sample collection is
      non-invasive and it can process larger numbers of samples with smaller amounts of
      antigen.

PMID- 14971703
TI  - Prevalence of infection with waterborne pathogens: a seroepidemiologic study in
      children 6-36 months old in San Juan Sacatepequez, Guatemala.
AB  - Water and sanitation interventions in developing countries have historically been
      difficult to evaluate. We conducted a seroepidemiologic study with the following
      goals: 1) to determine the feasibility of using antibody markers as indicators of
      waterborne pathogen infection in the evaluation of water and sanitation
      intervention projects; 2) to characterize the epidemiology of waterborne
      diarrheal infections in rural Guatemala, and 3) to measure the age-specific
      prevalence of antibodies to waterborne pathogens. Between September and December
      1999, all children 6-36 months of age in 10 study villages were invited to
      participate. We collected sufficient serum from 522 of 590 eligible children, and
      divided them into six-month age groups for analysis (6-12, 13-18, 19-24, 25-30,
      and 31-36 months). The prevalence of antibodies was lowest in children 6-12
      months old compared with the four older age groups for the following pathogens:
      enterotoxigenic Escherichia coli (48%, 81%, 80%, 77%, and 83%), Norwalk virus
      (27%, 61%, 83%, 94%, and 94%), and Cryptosporidium parvum (27%, 53%, 70%, 67%,
      and 73%). The prevalence of total antibody to hepatitis A virus increased
      steadily in the three oldest age groups (40%, 28%, 46%, 60%, and 76%). In
      contrast, the prevalence of antibody to Helicobacter pylori was relatively
      constant in all five age groups (20%, 19%, 21%, 25%, and 25%). Serology appears
      to be an efficient and feasible approach for determining the prevalence of
      infection with selected waterborne pathogens in very young children. Such an
      approach may provide a suitable, sensitive, and economical alternative to the
      cumbersome stool collection methods that have previously been used for evaluation
      of water and sanitation projects.

PMID- 14971704
TI  - Analysis of the replication kinetics of the ChimeriVax-DEN 1, 2, 3, 4 tetravalent
      virus mixture in Aedes aegypti by real-time reverse transcriptase-polymerase
      chain reaction.
AB  - The vector competence of mosquitoes for chimeric viruses being developed as
      vaccines to protect against dengue (DEN) virus infection were evaluated in a
      cooperative agreement with Acambis, Inc. Chimeric viruses have been constructed
      that contain the premembrane (prM) and envelope (E) genes of each of the wild
      type (wt) DEN virus serotypes, DEN-1, DEN-2, DEN-3, and DEN-4, in the yellow
      fever (YF) vaccine virus (strain 17D) YF-VAX backbone. It was previously shown
      that the replication profile of ChimeriVax-DEN2 virus in Aedes albopictus C6/36
      cells and in vivo in Ae. aegypti mosquitoes corresponded to that of YF-VAX virus;
      replication was restricted in C6/36 cells, and Ae. aegypti were poorly infected
      via an artificial infectious blood meal. Thus, there is very little risk of
      transmission by mosquitoes of ChimeriVax-DEN2 vaccine virus through the bite of a
      mosquito. However, because ChimeriVax-DEN 1, 2, 3, 4 viruses will be administered
      to humans simultaneously, growth of a mixture of ChimeriVax-DEN 1, 2, 3, 4
      viruses was assessed in both C6/36 cells in culture and in the Ae. aegypti
      mosquito, which is the primary vector of both YF and DEN viruses. Mosquitoes were
      intrathoracically (IT) inoculated with virus or fed a virus-laden blood meal, and
      the replication kinetics of ChimeriVax-DEN 1, 2, 3, 4 were compared with the wt
      DEN and YF-VAX viruses. A quantitative real-time reverse transcriptase-polymerase
      chain reaction assay was developed as a method to detect and differentiate
      replication of each of the four ChimeriVax-DEN serotypes in the ChimeriVax-DEN 1,
      2, 3, 4 tetravalent mixture. Growth of the chimeric viruses in C6/36 cells and in
      IT-inoculated Ae. aegypti was lower than that of YF-VAX virus; in previous
      studies Ae. aegypti was shown to be refractory to infection by YF-VAX virus. The
      growth rate of each chimeric virus was similar whether it was a single serotype
      infection, or part of the tetravalent mixture, and no interference by one
      chimeric virus over another chimeric serotype was observed. ChimeriVax-DEN
      viruses infected mosquitoes poorly via an infectious blood meal compared with wt
      DEN viruses. Therefore, it is unlikely that a mosquito feeding on a viremic
      vaccinee, would become infected with the chimeric viruses. Thus, there is very
      little potential for transmission by mosquitoes of the ChimeriVax-DEN vaccine
      viruses.

PMID- 14971705
TI  - Imported spotted fever rickettsioses in United States travelers returning from
      Africa: a summary of cases confirmed by laboratory testing at the Centers for
      Disease Control and Prevention, 1999-2002.
AB  - The increasing popularity of foreign travel and ecotourism places travelers at
      increased risk for certain tick-borne diseases. From 1999 through 2002, 31 cases
      of imported spotted fever-group rickettsioses (SFGR) in United States residents
      reporting travel to Africa were confirmed by laboratory testing at the Centers
      for Disease Control and Prevention. Nineteen patients (61%) reported visiting
      South Africa prior to illness onset. Most patients reported fever and one or more
      eschars; rash was reported for only 26% of the patients. Twelve patients had an
      initial non-reactive acute-phase serum sample obtained a median of three days
      after illness onset, and were confirmed by testing a second convalescent-phase
      serum sample obtained a median of 32 days after illness onset. Five patients were
      confirmed positive through immunohistochemical staining of skin biopsies,
      including three patients with acute-phase serum samples that tested negative for
      SFGR. This study emphasizes the importance of evaluating convalescent-phase serum
      specimens 28 days or more after illness onset or examining skin biopsies by
      immunohistochemical staining during early infection to confirm a diagnosis of
      imported SFGR.

PMID- 14971706
TI  - Hepatitis C virus and lymphoid malignancies.

PMID- 14971707
TI  - [Hyponatremia].

PMID- 14971708
TI  - [Diagnosis and therapy of hyponatremia].
AB  - Hyponatremia is associated with important morbidity, that includes the often
      fatal central pontine myelinolysis. It occurs more frequently in patients treated
      with diuretics, in liver cirrhosis, congestive heart failure and in the elderly.
      A sodium (Na) imbalance should be considered as highly probable in the presence
      of delirium, confusion, inappropriate behavior and coma. In the majority of cases
      hyponatremia is caused by Na depletion. This is associated with volume depletion,
      which, in turn, triggers thirst. The consequent reintroduction of solvent without
      solutes reconstitutes the volume lost, whilst further diluting Na. Less
      frequently an excess of solute-free water introduced orally or infused
      intravenously is retained in the presence of a reduced renal diluting capacity.
      Hyponatremia due to water excess may be distinguished from that caused by solute
      depletion by careful history taking, physical examination and by measurements of
      the body weight. Simple formulas, easily applicable to the bedside allow an
      accurate estimate of the water excess or solute deficit, and hence an accurate
      and effective quantitative correction of the alteration.

PMID- 14971709
TI  - [Clinical and diagnostic approach to erectile dysfunction].
AB  - Erectile dysfunction (ED), defined as the inability to achieve and/or maintain an
      erection sufficiently long for a satisfactory sexual performance or intercourse,
      is an important and common medical problem. ED is not a life-threatening
      disorder, but it influences the daily routine, social interactions, well-being
      and quality of life of the patient. Recent epidemiological data have shown a high
      prevalence and incidence of ED. The Massachusetts Male Aging Study found that 52%
      of men between the ages of 40 and 70 years reported ED with 9.6% having mild,
      22.2% moderate and 17.2% complete or severe ED. In a large Italian cross
      sectional study the overall prevalence of self-reported ED was 12.8% and the
      frequency of ED increases with age. ED may signal serious underlying and
      potentially life-threatening diseases, such as diabetes, hypertension,
      cardiovascular disease, peripheral vascular disease and other neurological and
      endocrine disorders. Also well documented is the role of some drug groups,
      certain types of surgery, injuries and the role of risk factors related to
      lifestyle such as smoking, alcohol consumption and inappropriate dietary habits
      accompanied by an abnormal serum level of cholesterol. The current availability
      of effective and safe oral drugs for ED in conjunction with the tremendous media
      interest in the condition, have resulted in an increasing number of men seeking
      help for ED. As a consequence, many physicians without background knowledge and
      clinical experience in the diagnosis of ED are involved in making decisions
      concerning the evaluation of such patients. The result of this is that some males
      with ED may undergo little or no evaluation before treatment is initiated and, in
      such circumstances, the disease causing the symptom (ED) may remain untreated.
      Baseline diagnostic evaluation for ED can identify the underlying pathological
      condition or the risk factors associated with ED in 80% of patients. This article
      reports a sequential approach for the diagnosis of ED that may diagnose
      reversible causes of ED and also unmask medical conditions that manifest with ED
      as the first symptom.

PMID- 14971710
TI  - [Chronic obstructive pulmonary disease: brief review].
AB  - The aim of this short review is to draw attention to chronic obstructive
      pulmonary disease (COPD), a clinical syndrome associated with emphysema and/or
      chronic bronchitis, in the light of the current scientific knowledge. The reason
      is that COPD has high socio-economic costs and the most recent projections place
      it among the first causes of mortality and morbidity due to chronic disease. The
      nosography, the clinical picture, including the systemic manifestations, the
      pathogenesis and the pathophysiological mechanisms, with special emphasis on
      expiratory flow limitation and pulmonary hyperinflation, leading to the most
      relevant symptoms and signs of the disease, have been reviewed. Finally a brief
      analysis of the costs due to the disease is also provided.

PMID- 14971711
TI  - [High and low grade gastric epithelial dysplasia: clinical management, endoscopic
      assessment of p53].
AB  - Epithelial dysplasia is considered the only one true histological marker of
      gastric cancer. In the present study we have evaluated the real clinical
      importance of epithelial dysplasia divided into low-grade (70 patients, mean age
      59.2 years) and high-grade (50 patients, mean age 58 years) dysplasia.
      Furthermore, it has been made a comparison with the corresponding endoscopic
      picture and an evaluation of the real meaning of p53 positivity. The clinical
      outcome subdivision of epithelial dysplasia was effected according to the
      criteria of Rugge: association with or progression to gastric cancer, persistence
      or regression. The endoscopic patterns have been divided into ulcerous lesions
      and non-ulcerous lesions. The immunohistochemical study has been carried out with
      the utilization of a p53 antibody (Dako, Glostrup, Denmark). From the analysis of
      the data it comes out that low-grade dysplasia is associated with or progressed
      to gastric cancer in a low percentage of cases (about 8.5%), while high-grade
      dysplasia is associated with or progressed to gastric cancer in a high percentage
      of cases (about 74%), by this proving itself to be a real histological marker of
      gastric cancer. The cases of epithelial dysplasia associated with or progressed
      to gastric cancer are significantly associated with an endoscopic picture of
      gastric ulcer (ulcer-cancer). Nonetheless, the cases of epithelial dysplasia in
      correspondence of non-ulcerous lesions have been noticed to be associated with or
      progressed to advanced gastric cancer. The evaluation of p53 did not positively
      correlate with the clinical progression of the epithelial dysplasia and with TNM
      classification in case of gastric cancer. Therefore, the evaluation of p53 does
      not represent a useful marker in the clinical practice.

PMID- 14971712
TI  - Body habitus changes, metabolic abnormalities, osteopenia and cardiovascular risk
      in patients treated for human immunodeficiency virus infection.
AB  - The aim of this study was to evaluate the influence of three variables--protease
      inhibitors, stavudine, and the length of combined therapy--on body habitus
      changes, metabolic effects and bone mineral density in HIV patients treated with
      highly active antiretroviral therapy (HAART). The onset of possible
      cardiovascular involvement was considered. Forty HIV patients (29 men and 11
      women, mean age 39.13 +/- 7.82 years, range 28-61 years) treated with HAART for
      12-43 months were evaluated for fat, lean, bone tissues, immunohematological and
      cardiovascular alterations. The differences in fat/lean tissues and bone mineral
      density were evaluated at dual-energy X-ray absorptiometry (DEXA). Serum lipids
      and the CD4/CD8 T-cell counts were recorded. ECGs were taken every 6 months;
      color Doppler echocardiography and color Doppler ultrasounds of the carotid
      vessels were performed in close chronological sequence with the second DEXA.
      Statistical analyses included: Student's t-test, Wilcoxon test, and single
      multiple regression analysis. Thirteen patients presented with fat loss, 7 fat
      accumulation, and 20 a combined form of both. The changes in the single body
      districts showed that the decrease in the limb fat is to be attributed to
      protease inhibitors, while none of the three variables was responsible for the
      decrease in the upper limb fat. The trunk weight increase was not significant.
      The decrease in the lean mass of the upper limbs is to be attributed to protease
      inhibitors, while none of the three variables was responsible for the increase in
      the lean mass of the upper and lower limbs. The decrease in bone mineral density
      was not significant. No treatment-related cardiovascular lesions were observed.
      In HIV patients treated with HAART for 12-43 months, the decrease in lower limb
      fat was due to protease inhibitors. Neither osteopenia nor cardiovascular
      diseases were observed during follow-up.

PMID- 14971713
TI  - Disseminated non-Hodgkin's lymphoma and chronic hepatitis C: a case report.
AB  - Hepatitis C virus (HCV) infection is occasionally associated to B-cell type non
      Hodgkin's lymphoma. Evidence showing a possible etiological link between HCV and
      lymphoma has been reported from areas of high HCV prevalence. We describe the
      case of a 68-year-old woman with B-cell non-Hodgkin's lymphoma mainly involving
      the skin. Typical manifestations of disease were cutaneous nodules, red-violet in
      color, scattered on the entire body and adherent to the subcutaneous tissue. A 3
      cm nodule excised from the leg was found at histology to consist of centroblastic
      like B cells, which stained positively for CD45, CD20 and CD79a. Although the
      patient was treated with different chemotherapy schedules, she died 1 year later
      with a diagnosis of disseminated lymphoma. Our report suggests that HCV, a
      trigger for clonal B-cell proliferation, predisposing to immunological disorders,
      such as mixed cryoglobulinemia and B-cell malignancies, may also account for the
      "rare" extranodal high-grade non-Hodgkin's lymphoma. Further observations suggest
      that treating HCV infection with antiviral therapy could help to prevent the
      development of B-cell non-Hodgkin's lymphoma.

PMID- 14971714
TI  - Flutamide-associated acute liver failure.
AB  - The nonsteroidal antiandrogenic drug flutamide [4'-nitro-3'
      (trifluoromethyl)isobutyranilide] is a safe and generally well-tolerated drug
      used for the treatment of prostate cancer. We describe the case of a 74-year-old
      male who developed life-threatening acute liver failure during flutamide therapy.
      Other causes of acute liver failure were appropriately ruled out and there was no
      evidence of active prostate cancer or liver metastases. The use of the Naranjo
      probability scale indicated a highly probable relationship between the
      development of acute liver failure and flutamide therapy. Severe liver
      dysfunction has been rarely documented in patients treated with flutamide, even
      though cases of fulminant liver failure have been described. A few cases have
      been reported also among patients with hirsutism being treated with flutamide.
      The mechanisms responsible for the occurrence of hepatotoxicity during treatment
      with flutamide are unknown. Mitochondrial dysfunction seems to be implicated. The
      potential of flutamide to act as a potent hepatotoxin should be borne in mind
      when treatment with this drug is being planned.

PMID- 14971715
TI  - [A letter on post-graduate education in internal medicine in the United States,
      published in the Annals].

PMID- 14971716
TI  - The effects of a herbal medicine (Mao-to) in patients with chronic hepatitis C
      after injection of IFN-beta.
AB  - We found that a herbal medicine (Mao-to) relieves the side effects of interferon
      (IFN)-beta and the combination therapy improves the biochemical response rate.
      However, the exact mechanism by which Mao-to is effective remains to be
      established. We conducted a controlled trial to clarify the effects of Mao-to.
      The study was carried out in 18 patients with chronic hepatitis C, and we
      examined subjective symptoms, body temperature and cytokines such as interleukin
      (IL)-beta, IL-1receptor antagonist (ra), IL-6 and TNF-alpha. Each patient
      received 6 million units of IFN-beta intravenously. Mao-to was given orally just
      before, just after, and 1 hour after IFN administration. The control study was
      carried out 6 months after the combination therapy of Mao-to and IFN-beta. The
      scores for general malaise, arthralgia and discomfort were significantly lower in
      the combination group than in control group. Body temperature did not
      significantly differ between the two groups. Plasma IL-6 level and IL-1ra were
      significantly elevated in the combination group compared to control (P = 0.0057
      and 0.0003, respectively). Mao-to did not affect plasma concentrations of IL
      1beta and TNF-alpha. We considered the increment of IL-1ra caused by Mao-to is to
      be one of the key factors involved in reducing the flu-like symptoms accompanying
      IFN-beta and improving the biochemical response rate.

PMID- 14971717
TI  - Flavonoid supplement improves leg health and reduces fluid retention in pre
      menopausal women in a double-blind, placebo-controlled study.
AB  - Flavonoid extracts derived from plant foods have been shown to benefit certain
      types of fluid retention. However, no studies have investigated these compounds
      for use in premenstrual fluid retention, a complaint common among women with
      otherwise normal menstrual cycles. Therefore, we conducted a double-blind,
      placebo-controlled, pilot study into the effect of a daily flavonoid extract
      (Colladeen, 320 mg oligomeric procyanidins) on premenstrual fluid retention.
      Fluid retention was assessed at baseline and throughout 4 menstrual cycles of the
      intervention using validated questionnaires. Leg girth was also measured at
      baseline and at the end of the study. Thirty subjects completed the study (n = 18
      active treatment; n = 12 placebo). Although no significant changes in leg girth
      measurements were noted, there was a significant improvement in subjective "leg
      health" scores after flavonoid treatment compared to placebo (p = 0.013).
      Furthermore, this was accompanied by an improvement in reported premenstrual
      fluid retention nearing significance (p = 0.066). We conclude that flavonoids
      supplements may provide a new therapeutic direction to counter premenstrual fluid
      retention and improve leg health. A larger study is now warranted.

PMID- 14971718
TI  - The effect of garlic on arteriosclerotic nanoplaque formation and size.
AB  - OBJECTIVE: In an in vitro biosensor model (PCT/EP 97/05212), the interplay
      between different lipoproteins in arteriosclerotic nanoplaque formation, as well
      as aqueous garlic extract (0.2-5.0 g/l from LI 111 powder) as a possible
      candidate drug against arterio/atherosclerosis were tested within the frame of a
      high throughput screening. METHODS: The processes described below were studied by
      ellipsometric techniques quantifying the adsorbed amount (nanoplaque formation)
      and layer thickness (nanoplaque size). A thorough description of the experimental
      setup has been given previously. RESULTS: Proteoheparan sulfate (HS-PG)
      adsorption to hydrophobic silica was monoexponential and after approximately 30
      min constant. The addition of 2.52 mmol/l Ca2+ led to a further increase in HS-PG
      adsorption because Ca2+ was bound to the polyanionic glycosaminoglycan (GAG)
      chains thus screening their negative fixed charges and turning the whole molecule
      more hydrophobic. Incubation with 0.2 g/l aqueous garlic extract (GE) for 30 min
      did not change the adsorption of HS-PG. However, the following addition of Ca2+
      ions reduced the increase in adsorption by 50.8% within 40 min. The adsorption of
      a second Ca2+ step to 10.08 mmol/l was reduced by even 82.1% within the next 40
      min. Having detected this inhibition of receptor calcification, it could be
      expected that the build-up of the ternary nanoplaque complex is also affected by
      garlic. The LDL plasma fraction (100 mg/dl) from a healthy probationer showed
      beginning arteriosclerotic nanoplaque formation already at a normal blood Ca2+
      concentration, with a strong increase at higher Ca2+ concentrations. GE,
      preferably in a concentration of 1 g/l, applied acutely in the experiment,
      markedly slowed down this process of ternary aggregational nanoplaque
      complexation at all Ca2+ concentrations used. In a normal blood Ca2+
      concentration of 2.52 mmol/l, the garlic induced reduction of nanoplaque
      formation and molecular size amounted to 14.8% and 3.9%, respectively, as
      compared to the controls. Furthermore, after ternary complex build-up, GE similar
      to HDL, was able to reduce nanoplaque formation and size. The incubation time for
      HDL and garlic was only 30 min each in these experiments. Nevertheless, after
      this short time the deposition of the ternary complex decreased by 6.2% resp.
      16.5%, i.e. the complex aggregates were basically resolvable. CONCLUSIONS: These
      experiments clearly proved that garlic extract strongly inhibits Ca2+ binding to
      HS-PG. In consequence, the formation of the ternary HS-PG/LDL/Ca2+ complex,
      initially responsible for the 'nanoplaque' composition and ultimately for the
      arteriosclerotic plaque generation, is decisively blunted.

PMID- 14971719
TI  - Characteristics, clinical effect profile and tolerability of a nasal spray
      preparation of Artemisia abrotanum L. for allergic rhinitis.
AB  - A nasal spray formulation containing an extract of Artemisia abrotanum L. was
      developed for therapeutic use in patients with allergic rhinitis and other upper
      airway disorders. The nasal spray preparation used contains a mixture of
      essential oils (4 mg/ml) and flavonols (2.5 microg/ml), of which some components
      have been shown to possess antiinflammatory, expectorant, spasmolytic as well as
      antiseptic and antimicrobial activities. The most important constituents in the
      essential oil fraction of the preparation are 1,8-cineole, linalool and davanone,
      while the flavonol fraction contains centauredin, casticin and quercetin dimethyl
      ethers. No trace of thujon was observed in the essential oil of the Artemisia
      abrotanum L. genotype "Tycho" used for the manufacture of the nasal spray
      preparation. In 12 patients with diagnoses of allergic rhinitis, allergic
      conjunctivitis and/or bronchial obstructive disease, the nasal spray was given
      immediately after the appearance of characteristic allergic nasal symptoms. In 10
      of the 12 patients, allergic rhinitis with nasal congestion, sneezing and
      rhinorrhea was dominant. After administration of the nasal spray, all patients
      experienced a rapid and significant symptom relief of nasal symptoms, comparable
      to the effect of antihistamine and chromoglicate preparations which several of
      the patients had used previously. The effect was present within 5 minutes after
      the administration and lasted for several hours. In 7 of the 10 rhinitis patients
      with concomitant symptoms of allergic conjunctivitis, a significant subjective
      relief of eye symptoms was also experienced. In 3 of the 6 patients who had a
      history of characteristic symptoms of endogenous, exogenous or exercise induced
      bronchial obstructive disease, there was a bronchial symptom relief by the nasal
      spray preparation which was experienced as rapid and clinically significant. It
      is concluded from the present proof of concept study, that a nasal spray
      formulation containing an extract characterised by a mixture of essential oils
      and flavonols from the Artemisia abrotanum L. genotype "Tycho", appears to be
      clinically useful and suitable for the prophylactic and therapeutic management of
      patients with allergic rhinitis and adjuvant symptoms.

PMID- 14971720
TI  - The herbal medicine Toki-shakuyaku-san improves the hypertension and intrauterine
      growth retardation in preeclampsia rats induced by Nomega-nitro-L-arginine methyl
      ester.
AB  - The chronic inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L
      arginine methyl ester (L-NAME) induces a preeclampsia-like syndrome including
      hypertension and intrauterine growth retardation (IUGR) in pregnant rats. We
      tested the traditional herbal medicine Toki-shakuyaku-san (TS) for beneficial
      effects in this model. L-NAME was infused subcutaneously into pregnant rats from
      day 14 of gestation. TS (1 g/kg, 2 g/kg) was administered by gavage from day 14
      to 20. Systolic blood pressure was measured on day 19. On day 20, rats were
      sacrificed and serum NO levels, placental weight, fetal body weight, fetal
      cerebrum weight and the thickness of the cerebral cortex were analyzed. TS (1
      g/kg, 2 g/kg) inhibited L-NAME-induced hypertension. The decrease in fetal body
      weight, cerebrum weight and thickness of the cerebral cortex was abrogated by TS
      (2 g/kg). The effect of TS on blood pressure was found only in the rats that were
      both pregnant and infused with L-NAME. L-arginine, at the amount equivalent to
      that contained in TS, showed no effect. Further, the change in serum NO levels
      induced by TS was only marginal. TS thus improved the hypertension and IUGR in
      preeclampsia rats induced by L-NAME in a NO-independent manner. These data
      suggested that TS may be beneficial for the treatment and prevention of
      preeclampsia.

PMID- 14971721
TI  - Nitric oxide-mediated vasorelaxation by Rhizoma Ligustici wallichii in isolated
      rat thoracic aorta.
AB  - The vasorelaxant effect of Rhizoma Ligustici wallichii and its possible mechanism
      of action on the vasomotor tone of the rat thoracic aortic rings were examined in
      an organ bath. Chloroform extracts of Rhizoma Ligustici wallichii (Ch1LW)
      elicited a dose-dependent, transient, relaxing response in endothelium-intact rat
      aorta contracted with norepinephrine (NE). This relaxant effect was abolished by
      removal of the endothelium and also by pretreatment with nitric oxide synthase
      inhibitors. Neither a muscarinic receptor antagonist nor a cyclooxygenase
      inhibitor altered the Ch1LW-induced relaxation. Tetramethylpyrazine, derived from
      Rhizoma Ligustici wallichii as a potent vasodilating component, induced a
      complete relaxation in both endothelium-intact and denuded rat aortas contracted
      by NE, but nitric oxide synthase inhibitors did not affect the relaxation. Ch1LW
      induced endothelium-dependent relaxation was mediated by nitric oxide released
      from the endothelium, and could be caused by component(s) other than
      tetramethylpyrazine.

PMID- 14971722
TI  - Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa
      seeds, in mice.
AB  - The anticonvulsant effects of thymoquinone, the major constituent of Nigella
      sativa seeds, were investigated using pentylenetetrazole (PTZ)- and maximal
      electroshock (MES)-induced seizure models. We also studied the effect of
      thymoquinone on pentobarbital-induced hypnosis, locomotor activity, and motor
      coordination. In PTZ-induced seizure, the intraperitoneally injection of
      thymoquinone with doses of 40 and 80 mg/kg, prolonged the onset of seizures and
      reduced the duration of myoclonic seizures. The protective effect of thymoquinone
      against mortality was 71.4% and 100% in the mentioned doses, respectively. In MES
      model, thymoquinone failed to reduce the duration of seizure, whereas exhibited a
      complete protection against mortality. In PTZ model, flumazenil (10 mg/kg, i.p.),
      an antagonist of benzodiazepine (BZD) site in the GABAA-BZD receptor complex,
      inhibited the prolongation of seizure latency, but did not show any effect on the
      duration of myoclonic seizures. Also, pretreatment with naloxone (0.1 and 03
      mg/kg, i.p.) inhibited the prolongation of myoclonic seizure latency and
      antagonized the reduction of myoclonic seizure duration induced by thymoquinone
      (40 and 80 mg/kg) in the PTZ model. Moreover, thymoquinone (40 and 80 mg/kg) did
      not have any hypnosis effect in the pentobarbital-induced hypnosis, but impaired
      the motor coordination and reduced the locomotor activity. These results indicate
      that thymoquinone may have anticonvulsant activity in the petit mal epilepsy
      probably through an opioid receptor-mediated increase in GABAergic tone.

PMID- 14971723
TI  - Histaminergic effect of crude papaya latex on isolated guinea pig ileal strips.
AB  - In the present study, we investigated the effect of the crude latex of Carica
      papaya L. (CPX) on isolated guinea pig ileal strips. CPX (0.5-512 microg/ml)
      caused concentration-dependent contraction of ileal strips suspended in Tyrode
      solution. The concentration of atropine (0.69 microM) that significantly blocked
      the contractile effect of acetylcholine on the isolated guinea pig ileum showed
      no significant effect on CPX- and histamine-induced contractions of the ileal
      strips. Mepyramine (87.6 nM) significantly blocked the contractile effect of
      histamine and CPX on the ileum. The same concentration of mepyramine, however,
      had no significant effect on acetylcholine-induced contraction of the isolated
      ileal strips. Removal of Ca2+ from the bathing medium abolished ileal
      contractions induced by acetylcholine, histamine and CPX. All the test substances
      were able to provoke ileal contractions after replacement of the Ca(2+)-free
      solution with Tyrode solution. Furthermore, 10(-5) M of nifedipine, a Ca(2+)
      entry antagonist, reversibly inhibited the contractile effect of all the test
      substances on the ileal strips. Results of this study together appear to show
      that CPX-induced contraction of the isolated guinea pig ileum is mediated via H1
      receptors and dependent on extracellular Ca2+ influx.

PMID- 14971724
TI  - Studies on the acute and sub-chronic toxicity of the essential oil of Ocimum
      gratissimum L. leaf.
AB  - Oral and intra-peritoneal acute toxicity and the sub-chronic intra-peritoneal
      toxicity of the essential oil of Ocimum gratissimum Linn, Lamiaceae (Ocimum oil),
      was investigated. The acute toxicity test involved the oral and intra-peritoneal
      administration of graded doses of Ocimum oil prepared as a 4% v/v emulsion to 2
      groups each of 30 rats and mice. LD50 and LD100 were determined for both routes
      and species. In the sub-chronic toxicity study, 25 male Sprague-Dawley rats were
      randomized into 4 test groups (treated with three graded sub-lethal doses of
      Ocimum oil prepared as a 4% v/v emulsion) and a control. Organs and blood samples
      were taken for analyses after a 30 day treatment period. A dose-dependent
      sedative effect of Ocimum oil was observed during the acute toxicity study in
      mice and rats and in the sub-chronic test in rats. Evidence of treatment, route,
      and dose-dependent toxicity were detected in both studies. Changes in weight of
      the testes, hearts, kidneys, intestines and lungs of the rats were statistically
      insignificant (ANOVA P < 0.05). Data analyses of blood biochemical,
      haematological and histopathological findings showed significant differences
      between control and treated groups and revealed that Ocimum oil is capable of
      invoking an inflammatory response that transits from acute to chronic on
      persistent administration. While the study revealed that Ocimum oil might be
      better tolerated when administered orally for systemic delivery, the oil has
      toxic potentialities that should not be overlooked.

PMID- 14971725
TI  - Action of different monoterpenic compounds against Anisakis simplex s.l. L3
      larvae.
AB  - Different natural monoterpenes (geraniol, citronellol, citral, carvacrol,
      cuminaldehyde and eugenol) are studied in vitro against Anisakis simplex s.l. L3
      larvae, employing perillaldehyde as a reference substance. Final concentrations
      used were: 12.50, 6.25 and 3.12 microg/ml for each of the tested products. The
      parameters average survival, survival 50 and maximum survival were determined at
      4, 8, 24 and 48 hours after the start of the experiment. All tested products,
      except eugenol, were active at the highest concentration (12.50 microg/ml). The
      damage caused to A. simplex s.l. L3 was by examining histological sections. The
      antioxidant activity of the tested products by DPPH free radical scavenging does
      not appear to be associated with their larvicide activity against A. simplex s.l.
      L3.

PMID- 14971726
TI  - Acute cholestatic hepatitis caused by Teucrium polium L.

PMID- 14971727
TI  - Modulatory effect of Piperine on mitochondrial antioxidant system in
      Benzo(a)pyrene-induced experimental lung carcinogenesis.
AB  - Chemoprevention has emerged as a very effective preventive measure against
      carcinogenesis. Many bioactive compounds present in edible as well in herbal
      plants have revealed their cancer chemopreventive potential. In the present
      study, our goal was to investigate the impact of piperine, a principle ingredient
      of pepper, on alterations of mitochondrial antioxidant system and lipid
      peroxidation in Benzo(a)pyrene (B(a)P) induced experimental lung carcinogenesis.
      Oral supplementation of piperine (50 mg/kg body weight) effectively suppressed
      lung carcinogenesis in B(a)p induced mice as revealed by the decrease in the
      extent of mitochondrial lipid peroxidation and concomitant increase in the
      activities of enzymatic antioxidants (superoxide dismutase, catalase and
      glutathione peroxidase) and non enzymatic antioxidant (reduced glutathione,
      vitamin E and vitamin C) levels when compared to lung carcinogenesis bearing
      animals. Our data suggests that piperine may extent its chemopreventive effect by
      modulating lipid peroxidation and augmenting antioxidant defense system.

PMID- 14971728
TI  - Leishmania donovani-derived lipophosphoglycan plus BCG induces a Th1 type immune
      response but does not protect Syrian golden hamsters (Mesocricetus auratus) and
      BALB/c mice against Leishmania donovani.
AB  - The efficacy of Leishmania donovani-derived lipophosphoglycan (LPG) plus
      Mycobacterium bovis Bacille Calmette-Guerin (BCG) as a vaccine candidate against
      visceral leishmaniosis in susceptible BALB/c mouse and Syrian golden hamster
      (Mesocricetus auratus) models was investigated. Following a triple vaccination
      with a total dose of 150 microl BCG plus 60 microg or 30 microg of LPG for
      hamsters and BALB/c mice respectively, there were no noticeable side effects both
      locally and systemically; implying that the molecule was safe at this dosage
      level. Vaccinated animals demonstrated an activation of both the humoral as well
      as cell-mediated responses to LPG, which correlated with resistance against the
      disease. Protection by LPG plus BCG, was however, poor as the remaining immunized
      animals showed disease progression leading to severity of the disease as
      illustrated by emaciation, mass loss and heavy splenic parasitaemia in hamsters.
      These data nevertheless suggest that it may be rewarding to further evaluate the
      potential of LPG as a vaccine candidate in leishmaniosis using other adjuvants,
      which may enhance its immunogenicity.

PMID- 14971729
TI  - Seasonal evolution of faecal egg output by gastrointestinal worms in goats on
      communal farms in eastern Namibia.
AB  - As a more detailed continuation of a previous study, faecal samples for worm egg
      counts were collected per rectum from ten marked adult animals in selected flocks
      of goats, in each of six villages evenly spread out in the communal farming
      district of Okakarara in eastern Namibia. The study was conducted on a monthly
      basis from August 1999 to July 2000. Average faecal worm egg counts (FECs) were
      highest during the warm-wet season, much lower during the cold-dry months and
      moderate during the hot-dry season. Least square means of FECs were 2140, 430 and
      653 per gram of faeces for the three seasons, respectively. Seasonal variation in
      egg counts was significant (P < 0.0001). Gastrointestinal strongyles, and to a
      lesser extent Strongyloides species, were the predominant parasite groups
      identified in goats. Kidding rates peaked in the cold-dry season and mortality
      rates in the hot-dry season. Results of this study suggest that gastrointestinal
      parasitism may be a problem that accentuates the effect of poor nutrition on
      small ruminants during the season of food shortages in the east of Namibia and
      that the use of FECs per se to assess the severity of gastrointestinal parasitic
      infection in goats followed by chemoprophylactic strategic and/or tactical
      treatment, may not be the best approach to addressing the worm problem under
      resource-poor conditions. The use of the FAMACHA system that identifies severely
      affected animals for treatment is technically a better option for communal
      farmers.

PMID- 14971730
TI  - Molecular analysis of bovine viral diarrhoea virus isolates from South Africa.
AB  - The presence of bovine viral diarrhoea virus in South Africa has been confirmed
      by several serological surveys. However, little is known about its biological
      properties. Twenty five isolates obtained by isolation in tissue culture and
      detected by means of the antigen capture ELISA from clinically sick cattle and
      from foetal calf serum in South Africa were characterized on the basis of
      analysis of the 5' non-translated (NTR) region of the genome. A reverse
      transcription polymerase chain reaction (RT-PCR) was used to amplify specific
      sequences from the 5'NTR of the genome. The oligonucleotide primers corresponding
      to positions 105-125 and 399-378, respectively, in the sequence of BVDV strain
      NADL were used to generate the PCR products. Both strands were sequenced directly
      with these primers and fluorescence-labelled dideoxynucleotides in an automated
      nucleic acid sequencer. Reference strains of pestiviruses [(BVDV type I, BVDV
      type II, border disease virus (BDV) and hog cholera virus (HCV)] and isolates
      from a previous investigation on BVDV in southern Africa were included for
      comparative purposes. All the BVDV strains obtained during this study belong to
      subgroups of BVDV genotype I. No association could be demonstrated between the
      geographic origin of the isolates. A number of isolates formed another branch
      separate from the existing branches Ia, Ib and Ic. These findings suggest that
      extensive genetic diversity can be found within BVDV type I isolates from
      southern Africa. Isolates that group with the classical BVDV type I strains,
      particularly of American origin, coexist with variants that appear to represent a
      local genetic pool and or variants evolving from the classical strains.

PMID- 14971731
TI  - General morphology of the oral cavity of the Nile crocodile, Crocodylus niloticus
      (Laurenti, 1768). I. Palate and gingivae.
AB  - The heads of nine 2.5 to 3-year-old Nile crocodiles (Crocodylus niloticus) were
      obtained from a commercial farm where crocodiles are raised for their skins and
      meat. The animals from which these specimens originated were clinically healthy
      at the time they were slaughtered. A detailed description of the macroscopic and
      microscopic features of the palate and gingivae of the Nile crocodile is
      presented and the results are compared with published information on this species
      and other Crocodylia. The histological features are supplemented by information
      supplied by scanning electron microscopy. Macroscopic features of interest are
      the small conical process situated at the base of the first two incisors of the
      maxilla, the distribution of cobbled units on the palate, and the broad dentary
      shelf forming the rostral aspect of the mandible. Histologically the palate and
      gingivae did not differ significantly from each other and both regions showed a
      presence of Pacinian-type corpuscles. Two types of sensory structures (taste
      receptors and pressure receptors) were identified in the regions examined, both
      involving modification of the epithelium and the underlying connective tissue.

PMID- 14971732
TI  - The heart remembers: observations of cardiac memory in the Dorper sheep heart.
AB  - Memory is a property common to a diverse range of tissues. Cardiac memory has
      been demonstrated in the human, dog, rat and rabbit. This is a peculiar
      phenomenon, reflected in the T wave of the electrocardiogram. The heart is able
      to remember periods of alterations in the sequence of ventricular activation and
      once there is a return to a normal sequence of ventricular activation the T waves
      may manifest memory. Cardiac memory is noted when the T wave during normal
      ventricular activation retains the vector of the previous abnormal QRS complex,
      caused by a period of altered ventricular activation. Possible mechanisms of
      memory in the heart are alterations of the transient outward potassium current
      (I10) in ventricular myocytes and new protein synthesis inside myocytes. These
      two mechanisms operate in short- and long-term cardiac memory respectively.
      Currently, it is unknown whether memory may have adverse structural consequences
      in the heart. We were able to demonstrate memory in the hearts of Dorper wethers
      and this is the first report of cardiac memory in Dorper sheep.

PMID- 14971733
TI  - Review of blackfly (Diptera: Simuliidae) control in South Africa.
AB  - The medical, veterinary and economic importance of blackflies in South Africa,
      and the historical development of blackfly control programmes in various South
      African rivers, are reviewed in this paper. In 1996 it was estimated that
      blackflies can cause more than R 88 million damages per annum along the middle
      and lower Orange River where Simulium chutteri is considered the main pest
      species. A clear link between the construction of dams and the spread of the
      blackfly problem was shown. Four phases characterize the development of blackfly
      control in South Africa: (1) during the 1960s blackflies in the Vaal River were
      controlled with DDT; (2), during the 1970s and into the 1980s blackflies were
      controlled using water-flow manipulation; (3) when used at strategic times, water
      flow manipulation could be used to enhance the effect of natural predator
      populations; and (4) during the 1990s the organophosphate temephos and toxins
      produced by the bacterium Bacillus thuringiensis var. israelensis were tested for
      their efficacy against blackflies. The larvicides temephos and B. thuringiensis
      proved to be effective and are still used in several control programmes. The
      latest research focuses on the factors that influence adult blackfly survival and
      annoyance, as well as the development of methods that can be used to protect
      sheep from blackfly attacks.

PMID- 14971734
TI  - Occurrence, clinical manifestation and the epidemiological implications of
      naturally occurring canine trypanosomosis in western Kenya.
AB  - Domestic dogs were screened for Trypanosoma brucei infection using the
      haematocrit centrifugation technique as part of routine active surveillance
      exercises in the Busia and Teso districts of Kenya. The purpose was to assess the
      role of dogs as sentinels for the occurrence of human sleeping sickness. Out of
      200 dogs screened, five were found to be infected at the various test sites.
      These five succumbed to the disease within four weeks, and exhibited a distinct
      and pronounced corneal opacity before death. Blood from two naturally infected
      dogs were tested for the presence of the serum resistance associated (SRA) gene
      and one tested positive, confirming it as human infective (T. brucei rhodesiense)
      prevalence (0.5%). It is considered that the occurrence of this clinical sign
      could be used as an early warning prediction of future outbreaks. This type of
      prediction could form an integral part of an indigenous technical knowledge set
      in areas lying at the edges of the tsetse (Glossina) belts where T. brucei is the
      main trypanosome species that affects dogs. The occurrence of corneal opacity in
      dogs could indicate a rise in the levels of T. brucei a proportion of which could
      be human infective T. b. rhodesiense circulating in the population early enough
      before disease outbreak occurs. It is thought that during sleeping sickness
      epidemics the domestic dog will be the first casualty rapidly succumbing to
      disease long before it is noticed in man. Prompt prediction of disease outbreaks
      would thus enable early interventions that would reduce the morbidity, mortality
      and the general economic losses associated with sleeping sickness to be
      instituted.

PMID- 14971735
TI  - Population structure of Argas arboreus (Acari: Argasidae) ticks associated with
      seasonally abandoned mixed heronries, dominated by cattle egrets (Bubulcus ibis),
      in South Africa.
AB  - During winter populations of Argas arboreus from heronries of the cattle egret,
      Bubulcus ibis, in South Africa are composed of adults, with some predominance of
      males, and II-IV instar nymphs, in a state of diapause. The period of tick
      activity, including reproduction and development of eggs, larvae and N1 nymphs,
      is synchronized with the nesting and breeding season of their avian hosts. It
      begins during spring with the return of birds to the heronry, and ceases in
      autumn through induction of reproductive diapause in engorged females, and
      behavioural diapause in unfed nymphs and adult ticks. Many ticks showed
      morphological anomalies and malformations, the study of which could possibly be
      used for monitoring of environmental pollution.

PMID- 14971736
TI  - Characterisation of ACTH related peptides in ectopic Cushing's syndrome.
AB  - Adrenocorticotrophin (ACTH) is derived by cleavage from the precursor, pro
      opiomelanocortin (POMC), and depending on the degree of processing by the tissue
      or tumor, there is the potential for a number of ACTH-related peptides to be
      secreted from POMC expressing cells. Previous chromatographic approaches have
      indicated the presence of high molecular weight forms of ACTH in the human
      peripheral circulation. However a quantitative assessment of the degree of
      processing requires two-site immunoradiometric assays which distinguish ACTH
      precursors and ACTH. Using this approach, we have previously identified the
      precursors of ACTH (POMC and proACTH) in the circulation of normal subjects in
      the range 5-40 pmol/l, which suggests that processing in the normal pituitary
      cell is incomplete. This study aimed to examine the extent of POMC processing by
      tumors that give rise to Cushing's Syndrome as a means of evaluating its
      usefulness as a diagnostic marker. In a retrospective analysis of 86 patients
      with Cushing's Syndrome, 34/35 patients with pituitary tumors had low levels of
      ACTH precursors (below 100 pmol/l) and the mean ratio of ACTH precursors:ACTH was
      5:1 which indicates that these tumors do process POMC to ACTH relatively
      efficiently. In ectopic Cushing's Syndrome, it is unlikely that the extra
      pituitary tumor cells, process POMC as efficiently. Therefore increased
      prevalence of ACTH precursors in the circulation would be expected and this was
      substantiated by the large excess of ACTH precursors (139-18,000 pmol/l) in the
      circulation of the 51 patients with the ectopic ACTH Syndrome. The diagnostic
      accuracy of the measurement of ACTH precursors was then prospectively compared
      with a group of 62 patients undergoing the current "gold standard" test of
      inferior petrosal sinus sampling (IPSS). All those patients with ACTH precursors
      below a diagnostic cut-off of 100 pmol/l were subsequently shown to have
      pituitary tumors, whereas levels of >100 pmol/l were seen in the four patients
      with ectopic tumors. In comparison the IPSS had a specificity of 100% but a
      sensitivity of 93% and for these false negative results the ACTH precursors
      proved diagnostically useful. Therefore measurement of ACTH precursors offers a
      simple non-invasive diagnostic test for the differential diagnosis of Cushing's
      Syndrome which compares favourably with IPSS.

PMID- 14971737
TI  - Correlation of bcl-2 and bax with apoptosis in human pituitary adenomas.
AB  - Bcl-2 oncogene and Bax gene play an important role in regulating apoptosis. In
      the present study, the expression of bcl-2 and bax was investigated and
      correlated with apoptosis in a series of 81 pituitary adenomas. Bcl-2 and bax
      proteins were localized by immunohistochemistry and the histoscore (HSC) was
      assessed by multiplying the immunohistostaining grade (1 to 4) by the staining
      intensity grade (1 to 3). According to bcl-2/bax HSC the tumors were separated in
      group A when > or = 1 and group B when < 1. The apoptotic labeling index (ALI)
      was accessed by the in situ end-labeling (ISEL) technique. Bcl-2 protein was
      equally detected in functioning and nonfunctioning adenomas with statistically
      significant higher HSC in nonfunctioning tumors (P < 0.03). Bax protein was
      immunopositive in the substantial majority of adenomas with significantly higher
      HSC in functioning as compared to nonfunctioning adenomas (P < 0.0009). The ALI
      was significantly higher in functioning adenomas as compared to nonfunctioning
      adenomas (P < 0.04). In addition, ALI was significantly higher in group B than in
      group A (P < 0.004) and it was correlated with bax HSC (P < 0.004). Finally, the
      group B of bcl-2/bax significantly predominated in nonfunctioning tumors (P <
      0.0009) and in microadenomas (P = 0.05), as compared with functioning adenomas
      and macroadenomas respectively. In conclusion, our findings suggest that bcl-2
      and bax molecules play a role in the regulation of apoptotic mechanisms in
      pituitary adenomas.

PMID- 14971738
TI  - Pitfalls in the biochemical assessment of acromegaly.
AB  - The biochemical assessment for newly recognized acromegaly is in most, but not
      all patients straightforward. Although significant improvements in the methods of
      biochemical testing for acromegaly have recently been made, major pitfalls to the
      assessment of this disease still exist. A number of different schemes have been
      employed for the assessment of GH secretion in clinical practice. Random GH
      levels have been often used, but remain unreliable for the assessment of
      acromegaly. Mean GH levels are also frequently used to assess GH status, but are
      not specific for the diagnosis of acromegaly. Measurement of glucose suppressed
      GH levels is the preferred method for assessing GH secretion in acromegaly.
      However, it is essential to recognize that when using highly sensitive and
      specific GH assays, nadir GH levels can be < 1 microg/L after oral glucose in
      some patients with newly diagnosed acromegaly and postoperative patients with
      active disease. On the other hand, when using most clinically available
      commercial GH assays which are less sensitive and specific than those used in
      research studies, failure of GH suppression into the normal range set in these
      studies is not alone diagnostic of active acromegaly. In order to diagnose
      acromegaly, documentation of GH excess should be accompanied by elevation in
      levels of the GH dependent peptide, insulin-like growth factor I (IGF-I).
      Consideration also needs to be given to the clinical context in which GH and IGF
      I are being measured as both can be altered in a number of clinical settings
      other than acromegaly. Both IGF-I and GH evaluations are important and
      complimentary parts of the biochemical assessment of acromegaly.

PMID- 14971740
TI  - Xanthomatous pituitary lesions: a report of two cases and review of the
      literature.
AB  - We describe two young men with cystic pituitary enlargement on magnetic resonance
      imaging (MRI) causing hypopituitarism. The first patient presented acutely unwell
      with headache and vomiting associated with anterior and posterior pituitary
      dysfunction. The second patient presented with hypopituitarism after a long
      history of hypogonadism. In both cases yellow/brown fluid was found at surgery
      and histological examination revealed inflammatory infiltrate with foamy
      histiocytes, lymphocytes and multinucleated giant cells containing cholesterol
      clefts. Full recovery of pituitary function occurred after surgery in the first
      but not the second patient. The first case is the first documented case of
      xanthomatous hypophysitis with recovery of pituitary function following surgery.
      The cases differed in duration of disease, as indicated by the long history of
      symptoms, the histological finding of marked fibrosis and the lack of recovery of
      pituitary function in the second. Xanthomatous pituitary lesions categorized in
      the literature as xanthomatous hypophysitis, xanthogranulomatous hypophysitis and
      xanthogranuloma of the sellar region have overlapping histological features. Our
      two cases revealed histological features that do not fit completely into any of
      the categories but share features of all three. These findings suggest that the
      various xanthomatous lesions of the sellar region may be a spectrum of a common
      inflammatory process rather than distinct pathological entities.

PMID- 14971739
TI  - Novel pituitary ligands: peroxisome proliferator activating receptor-gamma.
AB  - Pituitary tumors cause considerable morbidity due to local invasion,
      hypopituitarism, or hormone hypersecretion. In many cases, no suitable drug
      therapies are available, and surgical excision is currently the only effective
      treatment. We have recently demonstrated abundant expression of nuclear hormone
      receptor PPAR-gamma in human pituitary tumors of different subtypes. PPAR-gamma
      activators (thiazolidinediones) induced G0-G1 cell-cycle arrest and apoptosis in
      human, and murine corticotroph, somatolactotroph, and gonadotroph pituitary tumor
      cells, and suppressed in vitro hormone secretion. In vivo development and growth
      of murine corticotroph, somatolactotroph and gonadotroph tumors, generated by
      subcutaneous injection of ACTH-secreting AtT20, PRL- and GH-secreting GH3, and LH
      secreting LbetaT2, and alpha-T3 cells, was markedly suppressed in rosiglitazone
      treated mice, and plasma ACTH, and serum corticosterone, GH, PRL and LH levels
      were attenuated in all treated animals. PPAR-gamma is an important novel
      molecular target in pituitary adenoma cells and as PPAR-gamma ligands inhibit
      tumor cell growth and ACTH, GH, PRL and LH secretion in vitro and in vivo,
      thiazolidinediones are proposed as a novel oral medical management for pituitary
      tumors.

PMID- 14971741
TI  - Demonstration of a chaos generator with two time delays.
AB  - We demonstrate a chaos generator involving two time delays and two nonlinear
      functions. Dynamic behaviors are numerically and experimentally observed. The
      complexity of the dynamics is discussed in terms of Lyapunov exponents and
      dimensions. The setup can provide a new architecture for enhancing message
      security in chaos encryption systems.

PMID- 14971742
TI  - Complete electromagnetic coherence in the space-frequency domain.
AB  - We show that the following properties of a random electromagnetic field are
      equivalent: (i) the field is spatially completely coherent in the sense of the
      recently introduced electromagnetic degree of coherence and (ii) the electric
      cross-spectral density tensor factors in the two spatial variables.

PMID- 14971743
TI  - Tunable fiber gratings fabricated in photonic crystal fiber by use of mechanical
      pressure.
AB  - The mode-coupling properties of tunable long-period fiber gratings (LPGs) formed
      in photonic crystal fibers (PCFs) are presented. The mode coupling from the
      fundamental core mode to a cladding mode of a PCF is obtained by use of periodic
      mechanical pressure. The strength and the wavelength of the resonant peak are
      tuned by adjusting the grating period and the pressure applied on the PCF.
      Contrary to the conventional fiber case, the resonant wavelength of the PCF LPG
      is decreased by increasing the periodicity.

PMID- 14971744
TI  - Single-transverse-mode 2.5-W holmium-doped fluoride fiber laser operating at 2.86
      microm.
AB  - A high-power tandem-pumped Ho3+, Pr3+-doped ZBLAN fiber laser is demonstrated.
      Using the free-running 1100-nm output from a diode-cladding-pumped Yb3+-doped
      silica fiber laser as the pump source, a maximum output power of 2.5 W was
      generated at a slope efficiency of 29% after the threshold of approximately 30 mW
      was reached. Saturation of the output is avoided with Pr3+ codoping, which allows
      single-transition output. The center wavelength of the output was 2.86 microm and
      the bandwidth at maximum power was approximately 15 nm.

PMID- 14971745
TI  - Noise statistics in optically preamplified differential phase-shift keying
      receivers with Mach-Zehnder interferometer demodulation.
AB  - We report an analysis of the noise statistics for an optically preamplified
      differential phase-shift keying (DPSK) receiver with balanced and single-port
      detections. It is found that identical signal-amplified spontaneous emission
      beating noise exists for bits 1 and 0 in DPSK balanced detection. It is also
      revealed that the bit error ratio (BER) of a DPSK receiver with balanced
      detection has no direct relation to the conventional Q factor. Moreover, an
      analytic BER expression for the DPSK balanced detection receiver is presented.

PMID- 14971746
TI  - Complex fiber grating structures fabricated by sequential writing with
      polarization control.
AB  - We propose a flexible method for fabricating complex fiber grating structures
      based on sequential writing for fiber gratings with polarization control of the
      UV source beam. Pure apodized as well as arbitrary phase-shifted fiber Bragg
      gratings (FBGs) can be fabricated in a single scan. Experimental examples of
      raised-cos2 apodized and dispersionless FBG filters are given to demonstrate the
      feasibility of this method.

PMID- 14971747
TI  - Long-period-grating-assisted optical add-drop filter based on mismatched twin
      core photosensitive-cladding fiber.
AB  - A noninterferometric optical fiber add-drop channel filter based on a mismatched
      twin-core photosensitive-cladding fiber and long-period fiber grating is
      demonstrated. With assistance from the fiber grating, co-directional spectrally
      selective cross coupling between the two cores can be realized with an efficiency
      of 90%.

PMID- 14971748
TI  - Mach-Zehnder interferometer formed in a photonic crystal fiber based on a pair of
      long-period fiber gratings.
AB  - We demonstrate implementation of an all-fiber Mach-Zehnder interferometer formed
      in a photonic crystal fiber (PCF). We formed the all-PCF Mach-Zehnder
      interferometer by mechanically inducing two identical long-period fiber gratings
      (LPGs) in the PCF. The spectral properties of a LPG and a LPG pair were
      investigated. The interference fringe formed within the stop band of the LPG pair
      varied with the period and the strength of the gratings, and the fringe spacing
      was decreased with increasing grating separation. From the fringe spacing
      measurement the differential effective group index of the PCF was calculated to
      be deltam approximately equal to 2.8 x 10(-3).

PMID- 14971749
TI  - Modeling of realistic cladding structures for air-core photonic bandgap fibers.
AB  - Cladding structures of photonic bandgap fibers often have airholes of noncircular
      shape, and, typically, close-to-hexagonal airholes with curved corners are
      observed. We study photonic bandgaps in such structures by aid of a two-parameter
      representation of the size and curvature. For the fundamental bandgap we find
      that the bandgap edges (the intersections with the air line) shift toward shorter
      wavelengths when the air-filling fraction f is increased. The bandgap also
      broadens, and the relative bandwidth increases exponentially with f2. Compared
      with recent experiments [Nature 424, 657 (2003)] we find very good agreement.

PMID- 14971750
TI  - Fiber ringdown pressure sensors.
AB  - An exploratory study on a novel fiber ringdown pressure sensor is presented. With
      this technique, pressure measurements are achieved in a time domain by
      measurement of ringdown times. The proof-of-concept device consists of a diode
      laser light source, two 2 x 1 fiber couplers, a section of fused-silica single
      mode fiber, a photodetector, and an electronic control. The sensor's performance
      in the areas of stability, repeatability, and dynamic range is explored. The
      results demonstrate the new concept of fiber pressure sensors and the technical
      feasibility of developing a new generation of fiber sensors for pressure
      measurements.

PMID- 14971751
TI  - Laser imaging system for determination of three-dimensional scalar gradients in
      turbulent flames.
AB  - An imaging system for the measurement of three-dimensional (3D) scalar gradients
      in turbulent hydrocarbon flames is described. Combined line imaging of Raman
      scattering, Rayleigh scattering, and CO laser-induced fluorescence (LIF) allows
      for simultaneous single-shot line measurements of major species, temperature,
      mixture fraction, and a one-dimensional surrogate of scalar dissipation rate in
      hydrocarbon flames, while simultaneous use of two crossed, planar LIF
      measurements of OH allows for determination of instantaneous flame orientation.
      In this manner the full 3D scalar dissipation can be estimated in some regions of
      a turbulent flame on a single-shot basis.

PMID- 14971752
TI  - Concentration-induced nonuniform power in tunable erbium-doped fiber lasers.
AB  - We report, for the first time to our knowledge, the presence of concentration
      induced nonuniform power in tunable erbium-doped fiber lasers. A theoretical
      model is proposed with pair-induced quenching taken into account. We obtain good
      agreement between numerical and experimental results of a high-concentration
      erbium-doped fiber ring laser with a large tuning range of over 100 nm. These
      findings are useful for the design of lasers with doped fibers.

PMID- 14971753
TI  - Effective suppression of beam divergence for a high-power laser diode bar by an
      external-cavity technique.
AB  - We describe effective suppression of beam divergence for a high-power laser diode
      bar by use of an external-cavity technique. Nineteen off-axis external-cavity
      laser diodes of the high-power laser diode are formed by feedback with a stripe
      mirror. At three times the threshold current, the diverging angle (1/e2) of the
      external-cavity laser diode bar is reduced to 1.5 degrees from 6.6 degrees (free
      running) with 14.1-W peak output power and 70.4% of the radiated power of the
      free-running state without the external cavity. This technique effectively
      improves the beam quality of the high-power laser diode bar.

PMID- 14971754
TI  - Sequential optical coherence tomography and confocal imaging.
AB  - We report a system capable of sequentially acquiring two en-face images of
      different depth resolutions. The two images are generated by use of different
      principles, optical coherence tomography (OCT) and confocal microscopy, and have
      depth resolutions, at present, of better than 20 microm and over 0.12 mm,
      respectively. The lower-depth-resolution image is ideal for target positioning
      before collection of stacks of en-face OCT images. Switching between the two
      types of image by flipping an opaque screen in the reference arm, coupled with
      self-adjusting gain operation of avalanche photodiodes in the receiver. We
      illustrate the usefulness of the system by imaging a leaf and an optic nerve in
      vivo.

PMID- 14971755
TI  - Enhanced terahertz bistability in a nonlinear Fabry-Perot resonator with n-type
      quantum wells.
AB  - The intrinsic bistable terahertz response of intersubband plasmons in wide n-type
      delta-doped quantum wells is predicted to be enhanced by a resonant Fabry-Perot
      cavity. With a simple low-Q resonator, the threshold for bistability is decreased
      by a factor of 2-3 compared with that for bare multiple quantum wells.

PMID- 14971756
TI  - Optical properties of structurally modified glasses doped with gold ions.
AB  - We report on the optical properties of a structurally modified silicate glass
      doped with Au ions. The area in the vicinity of the focal point of an 800-nm
      femtosecond laser in a glass sample became gray as a result of the formation of
      color centers after laser irradiation and turned red because of precipitation of
      Au nanoparticles after further annealing at 550 degrees C for 30 min. When the
      glass was excited by UV light at 365 nm, yellowish-white and orange-yellow
      emissions were observed in the laser-irradiated and the Au-nanoparticle
      precipitated area, respectively. An optical Kerr shutter experiment showed that
      the Au nanoparticle-precipitated glass had an ultrafast nonlinear optical
      response, and the third-order nonlinear susceptibility was estimated to be
      approximately 10(-11) esu.

PMID- 14971757
TI  - Application of the nonlinear crystal SrB4O7 for ultrafast diagnostics converting
      to wavelengths as short as 125 nm.
AB  - We used non-phase-matched second-harmonic generation (SHG) in the highly
      nonlinear but low-birefringence crystal SrB4O7 for temporal characterization
      (autocorrelation) of femtosecond UV pulses to convert these pulses to wavelengths
      as low as 125 nm, close to the transparency limit of SrB4O7. The sensitivity of
      this method was approximately 1 microJ at the fundamental for a repetition rate
      of 1 kHz. We also used SHG at longer wavelengths to estimate the three nonlinear
      coefficients of SrB4O7.

PMID- 14971758
TI  - Quasi-phase-matching engineering for spatial control of entangled two-photon
      states.
AB  - We show that transverse engineering of quasi-phase-matched geometries can be used
      to tailor the spatial mode function that describes the quantum state of photon
      pairs generated in spontaneous parametric down-conversion. We study several
      geometries and reveal how properly engineered gratings affect, in particular, the
      spatial correlations embedded in two-photon entangled states.

PMID- 14971759
TI  - Spectral broadening of continuous-wave monochromatic pump radiation caused by
      stimulated Brillouin scattering in optical fiber.
AB  - We experimentally show that, when stimulated Brillouin scattering is generated in
      optical fiber by use of monochromatic cw pump radiation, the transmitted pump
      radiation exhibits spectral broadening that is much narrower than the classical
      homogeneous gain-narrowed Brillouin bandwidth. The bandwidth is practically
      independent of the pump strength, fiber characteristics, and the waveguide
      induced inhomogeneously broadened bandwidth of the Stokes emission. We show that
      these properties arise from strong parametric coupling of the Stokes and pump
      signals in the pump-depletion region.

PMID- 14971760
TI  - Observation of self-trapping of light in walk-off-compensating tandems.
AB  - We report the first experimental observation, to our knowledge, of the self
      trapping of light in walk-off-compensating optical tandems. The experiment was
      conducted with picosecond light pulses in a ten-plate optically contacted tandem
      made of potassium titanyl phosphate prepared for phase matching along a special
      geometry featuring a huge local walk-off. The observation should open the door to
      the exploration of multicomponent soliton formation in new classes of materials
      and settings.

PMID- 14971761
TI  - Nonlinear signal-processing model for signal generation in multilevel two
      dimensional optical storage.
AB  - A two-dimensional optical storage (TwoDOS) format with binary modulation is being
      developed in which channel bits are arranged on a two-dimensional hexagonal
      lattice [W. M. J. Coene, in Optical Data Storage, Vol. 88 of OSA Trends in Optics
      and Photonics Series (Optical Society of America, Washington, D.C., 2003), pp. 90
      92]. The aim is to increase the capacity by a factor of 2 and the data rate by a
      factor of 10 over third-generation Blu-ray Disc technology. Following a route
      similar to that used in one-dimensional conventional optical storage [Jpn. J.
      Appl. Phys. 42, 1074 (2003)] could lead to a further increase in capacity by the
      addition of another dimension to writing data, such as the use of multiple levels
      instead of the two levels (pit and land) used in the binary TwoDOS disk format.
      We present a nonlinear signal-processing model for signal waveform generation as
      a function of the M-ary channel symbols, as well as simulated signal readouts for
      multilevel TwoDOS.

PMID- 14971762
TI  - Dark-line atomic resonances in submillimeter structures.
AB  - We present measurements of dark-line resonances excited in cesium atoms confined
      in submillimeter cells with a buffer gas. The width and contrast of the
      resonances were measured for cell lengths as low as 100 microm. The measured
      atomic Q factors are reduced in small cells because of frequent collisions of
      atoms with the cell walls. However, the contrast of coherent population trapping
      resonances measured in the small cells is similar in magnitude to that obtained
      in centimeter-sized cells, but substantially more laser intensity is needed to
      excite the resonance fully when increased buffer-gas pressure is used. The effect
      of the higher intensity on the linewidth is reduced because the intensity
      broadening rate decreases with buffer-gas pressure.

PMID- 14971763
TI  - Highly efficient mode-locked Yb:Sc2O3 laser.
AB  - Passive mode locking of the Yb:Sc2O3 laser is demonstrated. We investigate the
      laser performance with Ti:sapphire and diode-laser pumping. The laser is mode
      locked by use of a semiconductor saturable-absorber mirror and emits as much as
      0.8 W of power in the picosecond range with a pump efficiency as high as 47%.
      With dispersion compensation, pulses as short as 230 fs for an average power of
      0.54 W are obtained at 1044 nm. This is, to our knowledge, the first femtosecond
      oscillator based on an Yb-doped sesquioxide crystal.

PMID- 14971764
TI  - Energy spectrum of a nonstationary ensemble of pulses.
AB  - We introduce a new definition of the energy spectrum of a nonstationary ensemble
      of pulses that reduces to the usual ones in the limit of statistically stationary
      ensembles of signals and of fully temporarily coherent ensembles.

PMID- 14971765
TI  - Absolute-frequency measurements with a stabilized near-infrared optical frequency
      comb from a Cr:forsterite laser.
AB  - A frequency comb is generated with a chromium-doped forsterite femtosecond laser,
      spectrally broadened in a dispersion-shifted highly nonlinear fiber, and
      stabilized. The resultant evenly spaced comb of frequencies ranges from 1.1 to
      beyond 1.8 microm. The frequency comb was referenced simultaneously to the
      National Institute of Standards and Technology's optical frequency standard based
      on neutral calcium and to a hydrogen maser that is calibrated by a cesium atomic
      fountain clock. With this comb we measured two frequency references in the
      telecommunications band: one half of the frequency of the d/f crossover
      transition in 87Rb at 780 nm, and the methane v2 + 2v3 R(8) line at 1315 nm.

PMID- 14971766
TI  - Phase locking in four-wave Raman mixing for generation of an ultrashort laser
      pulse.
AB  - The emission lines generated by four-wave Raman mixing were coherently phased and
      provided an approximately 30-fs pulse without any loss of energy simply by
      passage of the pulse beam through molecular hydrogen.

PMID- 14971767
TI  - Broadband phase-coherent optical frequency synthesis with actively linked
      Ti:sapphire and Cr:forsterite femtosecond lasers.
AB  - We link the output spectra of a Ti:sapphire and a Cr:forsterite femtosecond laser
      phase coherently to form a continuous frequency comb with a wavelength coverage
      of 0.57-1.45 microm at power levels of 1 nW to 40 microW per frequency mode. To
      achieve this, the laser repetition rates and the carrier-envelope offset
      frequencies are phase locked to each other. The coherence time between the
      individual components of the two combs is 40 micros. The timing jitter between
      the lasers is 20 fs. The combined frequency comb is self-referenced for access to
      its overall offset frequency. We report the first demonstration to our knowledge
      of an extremely broadband and continuous, high-powered and phase-coherent
      frequency comb from two femtosecond lasers with different gain media.

PMID- 14971768
TI  - Climate change, ozone depletion and the impact on ultraviolet exposure of human
      skin.
AB  - For 30 years there has been concern that anthropogenic damage to the Earth's
      stratospheric ozone layer will lead to an increase of solar ultraviolet (UV)
      radiation reaching the Earth's surface, with a consequent adverse impact on human
      health, especially to the skin. More recently, there has been an increased
      awareness of the interactions between ozone depletion and climate change (global
      warming), which could also impact on human exposure to terrestrial UV. The most
      serious effect of changing UV exposure of human skin is the potential rise in
      incidence of skin cancers. Risk estimates of this disease associated with ozone
      depletion suggest that an additional peak incidence of 5000 cases of skin cancer
      per year in the UK would occur around the mid-part of this century. Climate
      change, which is predicted to lead to an increased frequency of extreme
      temperature events and high summer temperatures, will become more frequent in the
      UK. This could impact on human UV exposure by encouraging people to spend more
      time in the sun. Whilst future social trends remain uncertain, it is likely that
      over this century behaviour associated with climate change, rather than ozone
      depletion, will be the largest determinant of sun exposure, and consequent impact
      on skin cancer, of the UK population.

PMID- 14971769
TI  - Development of realistic high-resolution whole-body voxel models of Japanese
      adult males and females of average height and weight, and application of models
      to radio-frequency electromagnetic-field dosimetry.
AB  - With advances in computer performance, the use of high-resolution voxel models of
      the entire human body has become more frequent in numerical dosimetries of
      electromagnetic waves. Using magnetic resonance imaging, we have developed
      realistic high-resolution whole-body voxel models for Japanese adult males and
      females of average height and weight. The developed models consist of cubic
      voxels of 2 mm on each side; the models are segmented into 51 anatomic regions.
      The adult female model is the first of its kind in the world and both are the
      first Asian voxel models (representing average Japanese) that enable numerical
      evaluation of electromagnetic dosimetry at high frequencies of up to 3 GHz. In
      this paper, we will also describe the basic SAR characteristics of the developed
      models for the VHF/UHF bands, calculated using the finite-difference time-domain
      method.

PMID- 14971770
TI  - Comparison between TG-51 and TRS-398: electron contamination effect on photon
      beam-quality specification.
AB  - Two dosimetry protocols based on absorbed dose to water have recently been
      implemented: TG-51 and TRS-398. These protocols use different beam-quality
      indices: %dd(10)x and TPR20,10. The effect of electron contamination in
      measurements of %dd(10)x has been proposed as a disadvantage of the TG-51. For
      actual measurements of %dd(10)x in five clinical beams (Primus 6-18 MV, SL-75/5 6
      MV, SL-18 6-15 MV) a purging magnet was employed to remove the electron
      contamination. Also, %dd(10)x was measured in the different ways described in TG
      51 for high-energy beams: with a lead foil at 50 cm from the phantom surface, at
      30 cm, and for open beam. Moreover, TPR20,10 was determined. Also, periodic
      quality-control measurements were used for comparing both quality indices and
      variation over time, but D20,10 was used instead of TPR20,10 and measurements in
      open beam for the %dd(10)x determination. Considering both protocols, S(w,air)
      and kQ were calculated in order to compare the results with the experimental
      data. Significant differences (0.3% for kQ) were only found for the two high
      energy beams, but when the electron contamination is underestimated by TG-51, the
      difference in kQ is lower. Differences in the other cases and variations over
      time were less than 0.1%.

PMID- 14971771
TI  - Algorithms for optimal sequencing of dynamic multileaf collimators.
AB  - Dynamic multileaf collimator (DMLC) intensity modulated radiation therapy (IMRT)
      is used to deliver intensity modulated beams using a multileaf collimator (MLC),
      with the leaves in motion. DMLC-IMRT requires the conversion of a radiation
      intensity map into a leaf sequence file that controls the movement of the MLC
      while the beam is on. It is imperative that the intensity map delivered using the
      leaf sequence file be as close as possible to the intensity map generated by the
      dose optimization algorithm, while satisfying hardware constraints of the
      delivery system. Optimization of the leaf-sequencing algorithm has been the
      subject of several recent investigations. In this work, we present a systematic
      study of the optimization of leaf-sequencing algorithms for dynamic multileaf
      collimator beam delivery and provide rigorous mathematical proofs of optimized
      leaf sequence settings in terms of monitor unit (MU) efficiency under the most
      common leaf movement constraints that include leaf interdigitation constraint.
      Our analytical analysis shows that leaf sequencing based on unidirectional
      movement of the MLC leaves is as MU efficient as bi-directional movement of the
      MLC leaves.

PMID- 14971772
TI  - Evaluation of a TG-43 compliant analytical dosimetry model in clinical 192Ir HDR
      brachytherapy treatment planning and assessment of the significance of source
      position and catheter reconstruction uncertainties.
AB  - A simple, time efficient, analytical model incorporating heterogeneities and body
      dimensions around a point 192Ir source is generalized for accurate dosimetry
      around commercially available 192Ir brachytherapy sources. The generalized model
      was verified in dosimetry of a clinical 192Ir high dose rate prostate monotherapy
      application, involving 16 catheters and 83 source dwell positions, through
      comparison with corresponding treatment planning system data. The computational
      time efficiency and accuracy of the proposed model allowed the assessment of the
      impact that uncertainties in source dwell positions and catheter reconstruction
      may have on dose distributions, and how these could potentially affect the
      clinical outcome. Results revealed that a 0.1 cm catheter reconstruction
      uncertainty and a 0.15 cm source position uncertainty along the catheter lead to
      a dose uncertainty of less than 2% for doses lower than 200% of the prescribed
      dose, reaching up to 5% for points lying in close proximity to the catheters.
      These uncertainties were found to have no impact (less than 1%) on dose volume
      histogram results of both the planning target volume and the urethra. A catheter
      reconstruction uncertainty as high as 0.2 cm results in a dose uncertainty
      greater than 2%, reaching up to 9%, only for points inside the 150% contour.
      However, even in this case, the impact on dose volume histogram calculations is
      less than 3%.

PMID- 14971773
TI  - Design of adaptive treatment margins for non-negligible measurement uncertainty:
      application to ultrasound-guided prostate radiation therapy.
AB  - Daily imaging during the course of a fractionated radiotherapy treatment has the
      potential for frequent intervention and therefore effective adaptation of the
      treatment to the individual patient. The treatment information gained from such
      images can be analysed and updated daily to obtain a set of patient
      individualized parameters. However, in many situations, the uncertainty with
      which these parameters are estimated cannot be neglected. In this work this
      methodology is applied to the adaptive estimation of setup errors, the derivation
      of a daily optimal pre-treatment correction strategy, and the daily update of the
      treatment margins after application of these corrections. For this purpose a
      dataset of 19 prostate cancer patients was analysed retrospectively. The position
      of the prostate was measured daily with an optically guided 3D ultrasound
      localization system. The measurement uncertainty of this system is approximately
      2 mm. The algorithm finds the most likely position of the target maximizing an a
      posteriori probability given the set of measurements. These estimates are used
      for the optimal corrections applied to the target volume. The results show that
      the application of the optimal correction strategy allows a reduction in the
      treatment margins in a systematic way with increasing progression of the
      treatment. This is not the case using corrections based only on the measured
      values that do not take the measurement uncertainty into account.

PMID- 14971774
TI  - Modelling survival after treatment of intraocular melanoma using artificial
      neural networks and Bayes theorem.
AB  - This paper describes the development of an artificial intelligence (AI) system
      for survival prediction from intraocular melanoma. The system used artificial
      neural networks (ANNs) with five input parameters: coronal and sagittal tumour
      location, anterior tumour margin, largest basal tumour diameter and the cell
      type. After excluding records with missing data, 2331 patients were included in
      the study. These were split randomly into training and test sets. Date censorship
      was applied to the records to deal with patients who were lost to follow-up and
      patients who died from general causes. Bayes theorem was then applied to the ANN
      output to construct survival probability curves. A validation set with 34
      patients unseen to both training and test sets was used to compare the AI system
      with Cox's regression (CR) and Kaplan-Meier (KM) analyses. Results showed large
      differences in the mean 5 year survival probability figures when the number of
      records with matching characteristics was small. However, as the number of
      matches increased to > 100 the system tended to agree with CR and KM. The
      validation set was also used to compare the system with a clinical expert in
      predicting time to metastatic death. The rms error was 3.7 years for the system
      and 4.3 years for the clinical expert for 15 years survival. For < 10 years
      survival, these figures were 2.7 and 4.2, respectively. We concluded that the AI
      system can match if not better the clinical expert's prediction. There were
      significant differences with CR and KM analyses when the number of records was
      small, but it was not known which model is more accurate.

PMID- 14971775
TI  - X-ray fluorescence and energy dispersive x-ray diffraction for the quantification
      of elemental concentrations in breast tissue.
AB  - This paper presents improvements on a previously reported method for the
      measurement of elements in breast tissue specimens (Geraki et al 2002 Phys. Med.
      Biol. 47 2327-39). A synchrotron-based system was used for the detection of the x
      ray fluorescence (XRF) emitted from iron, copper, zinc and potassium in breast
      tissue specimens, healthy and cancerous. Calibration models resulting from the
      irradiation of standard aqueous solutions were used for the quantification of the
      elements. The present developments concentrate on increasing the convergence
      between the tissue samples and the calibration models, therefore improving
      accuracy. For this purpose the composition of the samples in terms of adipose and
      fibrous tissue was evaluated, using an energy dispersive x-ray diffraction
      (EDXRD) system. The relationships between the attenuation and scatter properties
      of the two tissue components and water were determined through Monte Carlo
      simulations. The results from the simulations and the EDXRD measurements allowed
      the XRF data from each specimen to be corrected according to its composition. The
      statistical analysis of the elemental concentrations of the different groups of
      specimens reveals that all four elements are found in elevated levels in the
      tumour specimens. The increase is less pronounced for iron and copper and most
      for potassium and zinc. Other observed features include the substantial degree of
      inhomogeneity of elemental distributions within the volume of the specimens,
      varying between 4% and 36% of the mean, depending on the element and the type of
      the sample. The accuracy of the technique, based on the measurement of a standard
      reference material, proved to be between 3% and 22% depending on the element,
      which presents only a marginal improvement (1%-3%) compared to the accuracy of
      the previously reported results. The measurement precision was between 1% and 9%
      while the calculated uncertainties on the final elemental concentrations ranged
      between 10% and 16%.

PMID- 14971776
TI  - Differential phase optical coherence probe for depth-resolved detection of
      photothermal response in tissue.
AB  - We describe a differential phase low-coherence interferometric probe for non
      invasive, quantitative imaging of photothermal phenomena in biological materials.
      Our detection method utilizes principles of optical coherence tomography with
      differential phase measurement of interference fringe signals. A dual-channel
      optical low-coherence probe is used to analyse laser-induced thermoelastic and
      thermorefractive effects in tissue with micrometre axial resolution and nanometre
      sensitivity. We demonstrate an application of the technique using tissue phantoms
      and ex-vivo tissue specimens of rodent dorsal skin.

PMID- 14971777
TI  - Analytic image reconstruction in local phase-contrast tomography.
AB  - Phase-contrast tomography is a non-interferometric imaging technique for
      reconstructing the refractive index distribution of a weakly absorbing object
      from a set of tomographic projection measurements. In many practical situations,
      the spatial resolution of the reconstructed image can be increased by minimizing
      the field of view (FOV) of the imaging system. When the object of interest is
      larger than the FOV, the measured projections are truncated and one is faced with
      a local tomography reconstruction problem. In this work, we analytically and
      numerically investigate the problem of reconstructing tomographic images from
      truncated phase-contrast projection data. A simple backprojection algorithm for
      reconstructing object discontinuities from truncated phase-contrast projection
      data is proposed and investigated that involves no explicit filtering of the
      projection data. We also investigate the use of the filtered backprojection
      algorithm and a local tomography reconstruction algorithm developed for
      absorption CT. These reconstruction algorithms are implemented and numerically
      investigated to corroborate our theoretical assertions.

PMID- 14971778
TI  - Characterization and suppression of edge and aliasing artefacts in iterative x
      ray CT reconstruction.
AB  - For the purpose of obtaining x-ray tomographic images, statistical reconstruction
      (SR) provides a general framework with possible advantages over analytical
      algorithms such as filtered backprojection (FBP) in terms of flexibility,
      resolution, contrast and image noise. However, SR images may be seriously
      affected by some artefacts that are not present in FBP images. These artefacts
      appear as aliasing patterns and as severe overshoots in the areas of sharp
      intensity transitions ('edge artefacts'). We characterize this inherent property
      of iterative reconstructions and hypothesize how discretization errors during
      reconstruction contribute to the formation of the artefacts. An adequate solution
      to the problem is to perform the reconstructions on an image grid that is finer
      than that typically employed for FBP reconstruction, followed by a downsampling
      of the resulting image to a granularity normally used for display. Furthermore,
      it is shown that such a procedure is much more effective than post-filtering of
      the reconstructions. Resulting SR images have superior noise-resolution trade-off
      compared to FBP, which may facilitate dose reduction during CT examinations.

PMID- 14971779
TI  - An in vitro study of a microbubble contrast agent using a clinical ultrasound
      imaging system.
AB  - Optimal insonation settings for contrast imaging are yet to be specified, mainly
      due to the lack of good understanding of the behaviour of the microbubbles. A
      satisfactory model that explains the behaviour of individual contrast agent
      scatterers has not yet been reported in the literature. An in vitro system based
      on a commercial scanner (ATL HDI3000) has been developed to investigate the
      backscatter of such agents. Suspensions of Definity were introduced in an
      anechoic tank. The frequency of transmitted ultrasound varied from 1 to 5 MHz,
      pulse period from 2 to 10 periods and peak negative acoustic pressure from 0.08
      to 1.7 MPa. The backscatter at the fundamental and second harmonic frequency
      windows from the agent was normalized in terms of the corresponding components of
      backscatter from a blood mimicking fluid suspension. The agent provided a
      dominant resonance effect at 1.6 MHz transmit frequency. Second harmonic
      normalized backscatter averaged around 9 dB higher than the fundamental. The
      normalized fundamental backscatter intensity was linear with peak negative
      pressure. The second harmonic at resonance peaked at 0.5 MPa suggestive of bubble
      disruption above such pressure. The system proved capable of illustrating the
      ultrasonic behaviour of Definity in vitro, and the investigation suggested
      particular insonation conditions for optimal image enhancement using Definity.

PMID- 14971780
TI  - Outcome of wheezing in early childhood.
AB  - In Acta Paediatrica 50 y ago, Boesen published a follow-up of children with
      "asthmatic bronchitis". Recent reinvestigations of children hospitalized because
      of wheezing in early childhood are remarkably consistent with Boesen's
      observations. CONCLUSION: Young children admitted to hospital because of wheezing
      have a clearly increased risk of subsequent asthma. Recent studies confirm
      Boesen's observations of the prognostic importance of eosinophilia and an inverse
      relation between age at admission with wheezing and risk of subsequent asthma.
      Allergy or atopic dermatitis is predictive of subsequent asthma, whereas family
      history of allergy has low predictive value in infants.

PMID- 14971781
TI  - Nutritional relevance of trans isomeric fatty acids in human milk.
AB  - Trans isomeric fatty acids amount to about 2% of the fatty acid composition of
      human milk in Europe, whereas lower values were seen in Africa, and higher values
      were reported for North-America. At least five human studies indicate that trans
      fatty acids may interfere with the metabolism of long-chain polyunsaturated fatty
      acids. CONCLUSION: Trans isomeric fatty acids in human milk should be regarded as
      a potential confounding variable in studies investigating the role of long-chain
      polyunsaturated fatty acids in the development of breastfed infants.

PMID- 14971782
TI  - The difficult balance between dietary polyunsaturated fatty acids.
AB  - The evidence emerging from developing countries indicates a wide variability in
      the fat composition of human milk. The linoleic:alpha linolenic acid ratios,
      suggested to be included within the range of 5:1 and 15[20]:1, tend to fluctuate,
      and could indicate the capability of humans to self-adapt according to different
      dietary and environmental conditions. CONCLUSION: When referring to optimal
      "standard" dietary intakes for infants, the complex interactions between genetics
      and environment should be considered in interpreting observations from different
      settings.

PMID- 14971783
TI  - Troponins in children and neonates.
AB  - Cardiac troponin T and cardiac troponin I--the biochemical markers of myocardial
      injury--are characterized by high specificity and sensitivity in comparison with
      other markers used in the past. CONCLUSION: Troponins have been studied in a wide
      range of clinical settings. Some of them are unique to paediatric care, but many
      questions, mainly concerning laboratory limitations and data interpretation in
      paediatrics, are still open to debate.

PMID- 14971784
TI  - Cataract in children.
AB  - Of the estimated 1.4 million children world-wide who are blind, cataract is
      responsible for an estimated 190,000 (14%). The incidence varies from 1 to
      3/10,000 live births or 10 per million of the total population in low-income
      countries. Early diagnosis, referral and surgery are important in improving
      results. A recent study from Sweden indicates that examination of babies in
      maternity wards results in earlier referral compared with well-baby clinics or no
      formal screening. CONCLUSION: It is important that standardized protocols be
      developed and implemented to screen children for ocular anomalies, especially
      cataract, before discharge from maternity units.

PMID- 14971785
TI  - Normal studies are essential for objective medical evaluations of children who
      may have been sexually abused.
AB  - The findings of carefully conducted research studies of non-abused children
      should be used in medical evaluations for suspected sexual abuse if they are to
      be legally defensible. These studies have shown that a "wide" hymenal opening and
      a "narrow" rim of hymen should not be used as markers of abuse. CONCLUSION: The
      study by Myhre and associates is another addition to a growing collection of good
      science in a field of medicine where objectivity is essential.

PMID- 14971786
TI  - Trans fatty acids in human milk in Poland and their association with
      breastfeeding mothers' diets.
AB  - AIM: To determine the content of trans fatty acids in human milk in relation to
      breastfeeding mothers' diet. METHODS: Samples of milk were collected from 100
      breastfeeding mothers and 7-d dietary records and anthropometry from 69 mothers
      were obtained. RESULTS: The following total trans fatty acids contents (median
      (lower-upper quartile); % wt/wt) in milk samples were determined: 1) data for
      Spring: colostrum--1.37 (1.00-2.00), mature milk at 5-6 wk of lactation--2.59
      (1.49-3.34) and at 9-10 wk of lactation--2.36 (1.55-3.92); 2) data for Autumn:
      colostrum--1.80 (1.42-2.48), mature milk at 5-6 wk of lactation--2.41 (1.79-4.31)
      and at 9-10 wk of lactation--2.77 (1.53-4.18). The major sources of trans fatty
      acids in mothers' diets were bakery products, confectionery and snacks. Mothers
      who had high level of trans isomers in their milk consumed significantly higher
      amounts of these products. CONCLUSIONS: Bakery products, confectionery and snacks
      are a major source of trans fatty acids in maternal diet in Poland. The levels of
      trans fatty acids in human milk may reflect the current diet of the mother as
      well as the diet consumed early in pregnancy.

PMID- 14971787
TI  - Seasonal and environmental effects on breast milk fatty acids in Burkina Faso and
      the need to improve the omega 3 PUFA content.
AB  - AIM: To determine the Burkinabe breast milk lipid content and fatty acid
      composition and to compare these values with the recommended adequate intakes.
      METHODS: The study comprised four cross-sectional surveys conducted in urban and
      rural Burkina Faso at two different times of the year: during a period of food
      shortage (lean season) and during a favourable food availability period (post
      harvest season). The subjects were apparently healthy mothers nursing 5-mo-old
      infants. A total of 70 urban and 52 rural mothers and 100 urban and 98 rural
      mothers, respectively, during the post-harvest season and the lean season,
      completed the surveys. The surveys were conducted in January-February 2001
      (urban) and 2002 (rural) corresponding to the post-harvest season, and in April
      May 1998 (urban) and 1999 (rural), which is the lean season, and were carried out
      during home visits. The families were informed of the objectives of the study and
      gave their consent to participate. Breast milk samples were collected from each
      mother and analysed for lipid and fatty acid concentrations. RESULTS: Noticeable
      breast milk characteristics were: low lipid content (30-35 g/L), high C6:0-C14:0
      saturated fatty acids (27%-33% total fatty acids), high linoleic acid (15%-20%
      total fatty acids) and unbalanced linoleic/alpha-linolenic acid (20:1 to 53:1)
      and long-chain omega6/long-chain omega3 (3.6:1 to 4.9:1) polyunsaturated fatty
      acid ratios. In all life conditions and food availability, linoleic acid was in
      excess of and alpha-linolenic was below the recommended adequate intakes. Over
      80% of breast milk samples had linoleic/alpha-linolenic acid and long-chain
      omega6/omega3 polyunsaturated ratios well above the recommendations. CONCLUSION:
      Improvement in breast milk omeag3 PUFA seems to be recommendable in Burkina Faso,
      where breastfeeding is the primary infant feeding practice.

PMID- 14971788
TI  - Effects of passive smoking on common respiratory symptoms in young children.
AB  - AIM: To observe the effects of fathers' smoking on respiratory symptoms in
      children between the ages of 6 mo and 5 y living in Tehran during the period
      January to December 2001. METHODS: The caregivers of 622 children attending
      resident-based clinics in two university hospitals were interviewed about the
      respiratory illnesses incurred by the child during the previous 12 mo and the
      smoking habits of those living with the child. Children who lived in households
      in which any person, other than the father, smoked were excluded. RESULTS: The
      analysis included 595 children, 40.6% of whom were living in homes where fathers
      smoked cigarettes. About 35% of smokers admitted to unrestricted smoking at home.
      In children not living with a smoker, 81.6% had experienced at least one episode
      of upper respiratory tract infection (URTI) during the previous year and the rate
      increased to 95.2% in passive smokers whose fathers were not restricted from
      smoking in front of the children, (p-value <0.01). A similar pattern was found
      for otitis media and asthma (p-value <0.05 and <0.01, respectively). The average
      number of URTI episodes during the previous year was significantly higher in
      children exposed to unrestricted smoking (p <0.01). CONCLUSION: The study
      outlines the detrimental effects of paternal smoking on the respiratory health of
      children from a part of world in which this problem has not been studied
      previously, and highlights the importance of educating fathers to alter their
      smoking habits so that even if they do not stop smoking altogether, they should
      discontinue smoking indoors.

PMID- 14971789
TI  - Adherence to antiretroviral therapy and its determinants in children with human
      immunodeficiency virus infection: a multicentre, national study.
AB  - AIM: To investigate rates and determinants of adherence to antiretroviral therapy
      in Italian children infected with the human immunodeficiency virus (HIV).
      METHODS: An observational, cross-sectional multicentre study was performed
      through a structured interview with the caregivers of HIV-infected children. The
      interview included quantitative information on adherence in the 4 d before
      interview. Sociodemographic, clinical and psychosocial characteristics of
      children were recorded. RESULTS: 129 children (median age 96 mo) were enrolled,
      of whom 94 were on highly active antiretroviral therapy (HAART). Twenty-one (16%)
      omitted more than 5% of total doses in 4 d and were considered non-adherent.
      However, only 11% of caregivers reported that therapy had been administered at
      the correct times. No significant difference was found between age and the stage
      of HIV infection. Children aware of their HIV status were less adherent.
      Individual drugs showed a broad adherence pattern and children who received HAART
      were more adherent. Children receiving therapy from foster parents were more
      adherent than those receiving drugs from biological parents or relatives.
      CONCLUSIONS: Adherence is a major problem in children. Psychological rather than
      clinical or sociodemographic features and types of drug are major determinants of
      adherence.

PMID- 14971790
TI  - Natural course of preclinical type 1 diabetes in siblings of affected children.
AB  - AIM: To define the dynamics of preclinical type 1 diabetes in siblings of
      affected children and to characterize the siblings experiencing a progressive
      process. METHODS: From 801 families taking part in the "Childhood Diabetes in
      Finland" (DiMe) Study, 715 initially unaffected siblings were graded into four
      stages of preclinical type 1 diabetes based on the initial number of disease
      associated autoantibodies detectable close to the time of diagnosis of the index
      case, while another classification system covering 641 of the siblings was based
      on a combination of the initial number of antibodies and the first-phase insulin
      response (FPIR) to intravenous glucose. RESULTS: Based on the first
      classification, there was a total of 95 siblings with initial signs of
      prediabetes, out of whom 34 (36%) progressed, 26 (27%) remained stable and 35
      (37%) regressed during prospective observation for a median of 3.6 y (range 0.01
      9.8 y). The siblings who progressed were younger, had a higher initial number of
      detectable autoantibodies, higher initial levels of various antibodies, with the
      exception of insulin autoantibodies, lower FPIR and a retarded glucose
      elimination rate in the first intravenous glucose tolerance test as compared with
      those that regressed. According to the second classification there were 41
      siblings with initial signs of prediabetes, among whom 23 (56%) progressed, 14
      (34%) remained stable and 4 (10%) regressed during the observation period.
      CONCLUSION: These data show that almost half of the siblings with signs of
      prediabetes at the time of diagnosis of the index case progressed further in
      their preclinical disease process during prospective observation. Young age, a
      strong humoral immune response to beta-cell antigens and reduced insulin
      secretory capacity appeared to be characteristic of those with a progressive
      process. Advanced and late prediabetes seem to represent a point of no return, as
      regression from these stages to no prediabetes was extremely rare.

PMID- 14971791
TI  - Relationship between vasoactive intestinal peptide and intrapulmonary vascular
      dilatation in children with various liver diseases.
AB  - AIM: To evaluate the potential of vasoactive intestinal peptide (VIP) as a
      pathogenic factor of intrapulmonary vascular dilatation (IVD) in hepatopulmonary
      syndrome (HPS). BACKGROUND: HPS comprises a triad comprising liver dysfunction,
      IVD and hypoxaemia. Although the pathogenesis of the process has not been
      elucidated, many vasodilating substances, such as VIP, have been implicated in
      the development of pulmonary vascular abnormalities. IVD can be detected by
      contrast-enhanced echocardiography (CEE) before the development of abnormal gas
      exchange. METHODS: Forty-two children (20M, 22F; mean age 4.39 +/- 4.17 y) with
      various liver diseases who attended the paediatric liver clinic of King
      Chulalongkorn Memorial Hospital between March 2000 and February 2001 were
      recruited to the study. Each patient was tested for transcutaneous O2 saturation,
      CEE (applying the agitated normal saline technique), liver function test and
      serum VIP level. RESULTS: Fourteen of the 42 patients (33%) were CEE positive.
      Only one of the 14 patients had associated hypoxia and clinical cyanosis. The
      serum VIP levels of children with liver disease were significantly higher than
      those of the controls (60.21 +/- 35.04 pg/ml vs 43.71 +/- 34.61 pg/ml, p = 0.03).
      CEE-positive children tended to have higher serum VIP levels than CEE-negative
      children (72.65 +/- 40.31 vs 53.99 +/- 31 pg/ml, p = 0.3). The serum VIP levels
      of biliary atresia (BA) patients with favourable outcomes (serum bilirubin < or =
      34 micromol/L) were not significantly different from those with unfavourable
      outcomes (serum bilirubin > 34 micromol/L) (42.95 +/- 14.53 pg/ml vs 66.07 +/-
      32.17 pg/ml, p = 0.5). CONCLUSIONS: CEE is a non-invasive test for early
      detection of IVD in children with liver disease. VIP is not solely responsible
      for the pathogenesis of IVD in HPS. Further studies are required to determine
      which substances cause the development of IVD.

PMID- 14971792
TI  - Crohn's-like ileo-colitis in patients affected by glycogen storage disease Ib:
      two years' follow-up of patients with a wide spectrum of gastrointestinal signs.
AB  - AIM: To investigate the presence of inflammatory bowel disease (IBD) and to
      evaluate the progression of bowel involvement after two years' follow-up in seven
      patients affected by glycogen storage disease type Ib (GSDIb). METHODS: Seven
      patients (5F, 2M, aged 4.5-20.6 y) entered the study. Bowel involvement was
      evaluated by ileocolonoscopy and specific IBD serologic markers. To evaluate
      disease activity, Paediatric Crohn's Disease Activity Index (PCDAI), terminal
      ileum wall thickness detected at ultrasonography (US), 99mTechnetium labelled
      autologous White Cell Scan (Tc-WCS) and barium meal with follow-through were
      investigated. RESULTS: Ileocolonoscopy and histology examination revealed
      variable degrees of bowel involvement in all patients. The results of serologic
      markers were indicative of a Crohn's-like ileocolitis. US and Tc-WCS, could
      clearly define patients with severe inflammatory involvement, but failed to
      identify all patients with mild to moderate disease. For the most severely
      affected patients, anti-inflammatory agents and steroids were prescribed, whereas
      nutritional therapy with polymeric formula and antibiotics were assumed by two
      other patients and antibiotics only by one patient. Granulocyte colony
      stimulating factor (G-CSF) was prescribed to all patients. Ileocolonoscopy and
      histology data improved in all patients. The assumption of G-CSF and/or gastric
      drip feeding (g.d.f.) was inversely associated with the PCDAI results (p < 0.05).
      CONCLUSION: IBD is common in patients affected by GSDIb independently of the
      severity of gastrointestinal signs and symptoms. Different therapeutic approaches
      can be used according to the severity of IBD. G-CSF treatment and g.d.f. can be
      protective factors for IBD.

PMID- 14971793
TI  - Simultaneous voiding cystourethrography and voiding urosonography reveals utility
      of sonographic diagnosis of vesicoureteral reflux in children.
AB  - AIM: To evaluate the diagnostic potential of voiding urosonography (VUS) compared
      with fluoroscopic voiding cystourethrography (VCUG) under identical conditions
      and to evaluate potential reasons for false-negative VUS results, particularly
      regarding bladder concentrations of the US contrast agent, Levovist. METHODS:
      Fifty-six paediatric patients (M/F 34/22, mean age 2.3 y, age range 1 mo-14 y)
      underwent simultaneous VUS and VCUG under identical conditions. The bladder was
      filled by simultaneous administration of Levovist and the X-ray contrast medium,
      DIP Conray. Levovist concentrations in bladders were calculated using amounts of
      Levovist injected and total DIP Conray infused when reflux was first observed in
      either procedure. RESULTS: Sensitivities of VUS and VCUG for detection of
      vesicoureteral reflux (VUR) were both 86%, assuming that VUR detected by either
      method represented a true-positive, and no reflux by either method represented a
      true-negative. Patients under 24-mo of age displayed a better VUS sensitivity, of
      94%. Levovist concentrations in bladders ranged from 1.8% to 23%, with older
      children tending to demonstrate increased bladder capacity and lower
      concentration. All VUS false-negative units displayed Levovist bladder
      concentrations of less than 5%. CONCLUSION: The present simultaneous study
      suggests that: 1) the two techniques demonstrate similar sensitivity for
      detection of reflux; 2) sustained Levovist bladder concentrations of below 5% may
      not allow detection of reflux on VUS; and 3) VUS represents a suitable technique,
      particularly for small children whose bladder capacity is not so large.

PMID- 14971794
TI  - Phentolamine administration increases blood S100B protein levels in pediatric
      open-heart surgery patients.
AB  - AIM: Phentolamine administration during open-heart surgery shortens the cooling
      and rewarming phases of cardiopulmonary bypass (CPB) and hastens weaning from
      mechanical ventilation and extubation. Data on the effects of phentolamine on
      cerebral circulation and function in this setting are lacking. This study reports
      the cerebral effects of phentolamine using blood S100B protein levels and the
      middle cerebral artery pulsatility index (MCA PI). METHODS: Sixty pediatric
      patients undergoing congenital heart disease repair were randomly assigned to
      receive either phentolamine 0.2 mg kg(-1) i.v. (n = 30) or placebo (n = 30)
      before the cooling and rewarming phases of CPB. Samples for S100B measurement
      were collected at seven predetermined time-points before, during and after
      surgery. MCA PI values were recorded at the same times as sampling. RESULTS:
      S100B blood levels were higher in the phentolamine-treated group than in controls
      after rewarming (3.53 +/- 1.88 vs 1.58 +/- 0.53 microg l(-1); p < 0.001),
      remained persistently higher at the end of surgery (2.95 +/- 0.91 vs 0.79 +/-
      0.21 microg l(-1); p < 0.001) and returned to normal ranges 12 h later than in
      the placebo group (p > 0.05). MCA PI values were also significantly higher at the
      end of surgery in the phentolamine-treated group (1.83 +/- 0.50 vs 1.22 +/- 0.34;
      p < 0.01). Cooling and rewarming times were shorter in the phentolamine-treated
      group (p < 0.01, for all). CONCLUSION: Despite improved peripheral vasodilatation
      and perfusion, phentolamine administration in pediatric open-heart surgery is
      correlated with increased cerebrovascular resistance and brain damage.

PMID- 14971795
TI  - Neurological assessment at five years of age in infants born preterm.
AB  - AIM: To evaluate the agreement between Touwen's neurological examination and a
      derived simplified one, created to be applied at the age of 5 y to infants born
      preterm. METHODS: 185 children born at a gestational age (GA) of <33 wk and/or
      with a birthweight <1501 g, free of cerebral palsy, underwent Touwen's
      neurological examination at a mean age of 5 y and 8 mo (5-6.5 y). One-hundred and
      seventy had a full examination and were included into the study. They were born
      at a mean GA of 30 wk (range 24-35 wk) with a mean birthweight of 1250 g (range
      600-2690 g). A simplified examination, based on the clinical experience of two of
      the authors, was created a priori. The data were reviewed retrospectively and the
      concordance between the two forms was assessed. The reviewers were blinded to the
      original categorization from the long form. RESULTS: On the basis of the original
      Touwen's neurological examination, the 170 children were classified into 122 with
      a normal neurological examination, 41 with grade 1 minor neurological dysfunction
      (MND) and 7 with grade 2 MND, giving 28% of the cohort with MND. The concordance
      between the two forms was excellent, with an agreement in 169 out of 170
      subjects. None of the infants with the most complex form of MND was
      misclassified. CONCLUSION: The simplicity of this examination could allow its
      diffusion and its use in follow-up programmes. It could improve the quality of
      routinely collected follow-up data of preterm neonates.

PMID- 14971796
TI  - Effect of methotrexate and folinic acid on skeletal growth in mice.
AB  - AIM: To investigate whether chronic administration of medium doses of
      methotrexate (MTX) causes suppression of skeletal growth in young mice and to
      determine whether folinic acid supplementation could reverse this effect.
      METHODS: Four equal groups of Balb/c young male mice (6 animals in each group;
      mean body weight 11.9 +/- 0.25 g, in their rapid growth phase) were subjected to
      the following drug treatment for a period of 3 wk. Group 1 was given
      intraperitoneal MTX (3.5 mg kg(-1) body weight) every second day. Group 2
      received folinic acid (7.0 mg kg(-1) body weight) intraperitoneally every second
      day. Group 3 was given both drugs (MTX every second day and folinic acid 8 h post
      MTX injection). Group 4 was injected with physiological saline every other day to
      serve as a control group. Total body weight of the animals in each group was
      monitored every second day for the entire study period. The animals were
      sacrificed, the bilateral femurs and tibias of each animal were harvested and X
      rays of the bones were taken. The length of each femur and tibia was measured
      using a micrometer. Measurements from the radiographs were also recorded using
      image analysis software. The MTX concentrations in the plasma and the folate
      levels in erythrocytes were determined. The heights of the distal femoral and the
      proximal tibial growth plate for each animal were measured on histological tissue
      sections. RESULTS: Mean lengths of both the tibia and femur of animals were
      compared in the four treatment groups. A significant decrease in the mean lengths
      (one-way ANOVA, p < 0.005) was observed in the group receiving MTX alone.
      Similarly, there was a significant decrease (p < 0.001) in the height of the
      femoral and tibial growth plate in this group when compared with the other
      groups. The main effect of MTX seemed to be on the hypertrophic proliferative
      zone of chondrocytes in the growth plate. Furthermore, animals in this MTX
      treated group also showed increased levels of MTX in plasma and low levels of
      erythrocyte folate. CONCLUSION: These data show that chronic administration of
      MTX induces suppression of skeletal growth in mice, possibly through the
      inhibition of the pathway of de novo DNA synthesis. Folinic acid treatment
      following MTX administration appears to reverse this growth inhibition. Based on
      these observations, children suffering from juvenile rheumatoid arthritis,
      osteosarcoma or acute lymphoblastic leukaemia and receiving MTX over long periods
      of time could be at risk of short-term suppression of skeletal growth. If this is
      the case, it is possible that they could benefit from dietary supplementation
      with folinic acid.

PMID- 14971797
TI  - Anogenital human papillomavirus in non-abused preschool children.
AB  - AIM: To estimate the prevalence of human papillomavirus (HPV) in anogenital
      samples from children selected for non-abuse. METHODS: A letter of invitation was
      sent to 2731 girls and 1042 boys, all of them aged 5 or 6 y. Inclusion was based
      on self-selection, whereby parents who did not suspect any occurrence of sexual
      abuse of their child gave informed consent to participate. Several mechanisms
      were undertaken to exclude abused children. A complete examination was done of
      each child, including anogenital examination with a colposcope and
      microbiological sampling from the genitals and anus. Polymerase chain reaction
      (PCR) using primers MY09 and MY11 was used to identify HPV, and sequencing was
      done on each positive amplicon. RESULTS: PCR was performed on 325 adequate
      specimens from 211 children enrolled. Seven samples from 5 girls were HPV
      positive, making 2/161 (1.2%) of the anal and 5/164 (3.0%) of the genital
      specimens positive. HPV was not detected in any of the boys. In four girls strong
      associations with HPV 6 genotypes were found, while one girl probably had a mixed
      infection with HPV 6 and 16. Three girls (1.8%) had clinically detectable
      anogenital warts. CONCLUSION: Since our results are comparable with a prevalence
      reported from allegedly abused children, and higher rates have been reported from
      the oral cavity in healthy children, we find detection of HPV unreliable as an
      indicator of sexual abuse in 5-6-y-old children. The rate of anogenital warts
      found in our study is comparable with a rate reported in abused children.

PMID- 14971798
TI  - Genital anatomy in non-abused preschool girls.
AB  - AIM: To describe the normal variations in genital anatomy in preschool girls
      selected for non-abuse. METHODS: A total of 2731 girls aged 5 or 6 y were invited
      to take part in the study; 195 girls were recruited. Inclusion was based on self
      selection, whereby parents who did not suspect any occurrence of sexual abuse of
      their children gave informed consent to participate. Several steps were taken to
      exclude abused girls and girls with previous accidental genital injuries. The
      genital examination, using a colposcope and a camera, was performed in supine
      position using a separation and traction technique, and in the prone knee-chest
      position. RESULTS: A number of genital anatomical features and hymenal
      measurements were described and found consistent with previous studies. An
      important finding was outward folding of the posterior hymenal rim in many girls,
      a feature that could be difficult to distinguish from attenuation of the
      posterior hymen. A gaping hymenal orifice, previously suggested to be a
      supportive sign of sexual abuse, was fairly frequently found and significantly
      associated with a large horizontal hymenal diameter. CONCLUSION: To distinguish
      between girls with outward folding of the posterior hymen and those with
      attenuated hymens, we recommend the use of the saline irrigation method. Even
      though normative hymenal measurement data now exist from a reasonable number of
      girls, these measurements should be used with caution in sexual abuse
      evaluations.

PMID- 14971799
TI  - Cardiac troponin I, cardiac troponin T and creatine kinase MB concentrations in
      umbilical cord blood of healthy term neonates.
AB  - AIMS: To measure and compare cardiac troponin I, cardiac troponin T and creatine
      kinase MB concentrations in the umbilical cord blood of healthy term infants and
      to investigate the relationship between maternal and neonatal troponin values at
      birth. METHODS: Troponin I, troponin T and creatine kinase MB concentrations were
      measured from the umbilical cord samples of 85 healthy term neonates and in the
      blood samples of their respective mothers at birth. RESULTS: Median
      (interquartile range) umbilical cord concentrations were 0 microg/L (0-0) for
      troponin I, 0 microg/L (0-0.019) for troponin T and 4.90 microg/L (3.90-6.61) for
      creatine kinase MB. Troponin I and T concentrations were higher than the
      detection limit for the assay in 2 (2.3%) and 41 (48.2%) neonates, respectively.
      Two mothers (2.3%) had cTnT levels above the detection limit; none of them had
      increased levels of cTnI. CONCLUSION: Probably owing to differences in expression
      and assay detection limits, cord blood troponin T concentrations are frequently
      over the detection limit at birth, while troponin I is mostly undetectable and
      comparable with that in healthy pregnant women. These cardiac regulatory proteins
      are of neonatal origin and are not influenced by maternal levels.

PMID- 14971800
TI  - Evaluation of screening procedures for congenital cataracts.
AB  - AIM: To evaluate the efficacy of two different Swedish screening procedures for
      early detection of congenital cataracts in comparison with no screening. METHODS:
      Children born between January 1992 and December 1998 in Swedish regions with an
      established eye-screening routine procedure, diagnosed with congenital cataract,
      and operated on before 1 y of age, were included in a retrospective study. Age at
      referral and age at time of the operation were compared between regions using
      different screening procedures: screening in the maternity wards (Region 1), at
      the well-baby clinics (Region 2) and one region without any screening (Region 3).
      RESULTS: Seventy-two children were included in the study. Concerning early
      diagnosis and surgery, Region 1 differed significantly from Regions 2 and 3,
      which were more similar and were combined for further analysis. The difference in
      detected cases was greatest at 21 d of age (55% vs 18%; p < 0.001), but persisted
      even at 100 d of age (78% vs 64%; p < 0.02). Region 1 screening resulted in more
      and earlier cases detected than the other two regions (22 vs 15 per 100,000
      births). In 72% of all cases, surgery was performed in response to referrals from
      either the maternity wards (36%), or the well-baby clinics (36%). However, half
      of the cases from the well-baby clinics were detected too late, i.e. at > 100 d.
      CONCLUSION: Eye screening in the maternity ward is preferable to well-baby clinic
      screening and to no screening at all, since it leads to early detection.
      Screening should also be performed routinely at well-baby clinics within the
      period when successful treatment is possible.

PMID- 14971801
TI  - Do adult patients with phenylketonuria improve their quality of life after
      introduction/resumption of a phenylalanine-restricted diet?
AB  - AIM: To evaluate the possible influence of dietary treatment on the quality of
      life of adult patients with PKU (phenylketonuria) following late introduction or
      resumption of a Phe-restricted diet. METHODS: Fifteen adult patients with
      classical PKU (10F, 5M; mean age: 27.5 y, range: 16.4-37.5 y) were selected for
      the study. These patients had either resumed a restricted diet after a period of
      discontinuation, or were placed on a restricted diet after late diagnosis. All of
      them were interviewed about their quality of life using a 24-item questionnaire.
      RESULTS: The index of dietary control was poor (median Phe: 954 micromol/L) in
      8/15 patients, regular (Phe: 514 micromol/L) in 4/15 and good (Phe: 354
      micromol/L) in 3/15 patients. Fifty-three percent of patients reported that their
      state of health was very good, 47% described it as good, and 40% felt that their
      present health on-diet was better than it had been off-diet; 53% believed that
      they were calmer, quieter and less easily upset and 40% were more alert and were
      more able to maintain attention while on-diet. Thirty-three percent of the
      patients felt happier, and 27% felt more vital; 20% thought that they were less
      impulsive and aggressive, and that they were now less argumentative than before.
      Sixty percent of the patients felt that their quality of life had improved on
      diet compared with the situation off-diet. CONCLUSION: More than half of our
      patients believed that their quality of life improved with a Phe-restricted diet;
      they reported feeling calmer, quieter, and less easily upset. Only 47% attained
      regular to good dietary control.

PMID- 14971802
TI  - Down syndrome and breastfeeding.
AB  - AIM: The aim of the study was to investigate the frequency of breastfeeding among
      children with Down syndrome. METHODS: The mothers of 560 children with Down
      syndrome attending four university hospitals in Italy were interviewed and the
      neonatal clinical records retrieved. Information was collected on the type of
      infant feeding and on why some mothers had not breastfed their children. Two
      groups of healthy children whose feeding habits had been previously investigated
      were recruited as control subjects (1601 and 714, respectively). A paediatrician
      in each hospital was interviewed about the neonatal admission policy of children
      with Down syndrome. RESULTS: Among the 560 Down children, 246 (44%) were admitted
      to the neonatal unit. Compared with the two control groups, children with Down
      syndrome were significantly more frequently bottle-fed (57% vs 15% and 24%,
      respectively, odds ratio 7.5, 95% CI 6.0-9.4 and 4.2, 95% CI 3.3-5.4.
      respectively). Only 30% of infants admitted to the neonatal unit were breastfed.
      The main reasons reported by the mothers for not having breastfed were infants'
      illness in infants who had been admitted to the neonatal unit and frustration or
      depression, perceived milk insufficiency and difficulty with suckling for those
      babies who had not been admitted to the unit. The paediatricians reported that
      the admission of a baby with Down syndrome to the neonatal unit could sometimes
      take place not for medical reasons, but for diagnostic work-up or for a more
      appropriate diagnosis and to maintain communication with the family. CONCLUSIONS:
      Down syndrome babies are less frequently breastfed compared with healthy
      children. Support in breastfeeding should become a relevant point of health
      supervision for children with Down syndrome.

PMID- 14971803
TI  - Body mass index for Saudi children with Down's syndrome.
AB  - AIM: Children with Down's syndrome (DS) have a higher prevalence of obesity than
      children without DS. This study aimed to assess the prevalence of
      overweight/obesity and to establish reference body mass index (BMI) percentile
      curves for Saudi children with uncomplicated DS below the age of 5 y. METHODS:
      BMI was measured prospectively in 785 children with DS and compared with 989
      Saudi children without DS. Both groups were compared with the international cut
      off point figures for age and gender. RESULTS: Obesity was not a prominent
      features in Saudi children with DS and their mean BMI curves were linear to the
      international cut-off points for BMI, indicating a clear tendency for overweight.
      BMI reference percentile curves were constructed. CONCLUSION: Reference curves
      for BMI worked out in this study, taken in conjunction with those for height and
      weight, will be useful in monitoring the size and shape of Saudi children with DS
      up to the age of 5 y.

PMID- 14971804
TI  - Lack of appropriate formulations of medicines for children in the community.
AB  - AIM: Appropriate formulations are essential in pharmacotherapy. This study
      surveyed the use of different formulations by children in the community, and
      examined the reported lack of appropriate formulations (oral solutions) in
      relation to the licensing status of drugs. METHODS: A cross-sectional study based
      on 68,019 pharmacy dispensing records was performed in The Netherlands. For each
      prescription the formulation was assessed, and all prescriptions were
      categorized: unlicensed (no product licence), off-label (licensed drugs used
      outside the licence terms) and authorized (licensed drugs used according to the
      licence). The types of formulation used were assessed in relation to age and
      licensing status. RESULTS: In all age groups, approximately half of all
      prescriptions were for oral drugs. The only major age-related trend was within
      oral drugs: younger children were more likely to be prescribed oral solutions.
      For authorized drugs the proportion of tablet/capsules exceeded oral solutions at
      the age of 7 y, whereas for off-label drugs this occurred at 3 y of age. For
      those medicines prepared by the pharmacy, tablets and capsules were more likely
      to be prescribed from the age of 9 y. CONCLUSION: Many children in the community
      receive inappropriate oral formulations. Regulatory authorities and the
      pharmaceutical industry need to ensure that children have access to medicines
      with appropriate formulations.

PMID- 14971805
TI  - Asthmatic bronchitis in children. Prognosis for 162 cases, observed 6-11 years.
      1953 [classical article].

PMID- 14971806
TI  - Unilateral submandibular suppurative sialadenitis in a premature infant.
AB  - Isolated submandibular suppurative sialadenitis is extremely rare in newborn
      infants and is associated with prematurity and prolonged gavage feeding. This
      report describes a premature infant who developed a life-threatening airway
      obstruction due to suppurative submandibular sialadenitis. The diagnosis was made
      on clinical grounds and confirmed by ultrasonography. Staphylococcus aureus was
      grown from the pus expressed from the Wharton's duct orifice. Upper airway
      obstruction and respiratory failure were managed with intubation and mechanical
      ventilation, and the sialadenitis resolved quickly and completely with
      flucloxacillin treatment. Possible causes of sialadenitis include dehydration,
      decreased saliva flow and stasis during gavage feeding, duct obstruction by
      stones and direct bacterial inoculation. Ultrasonography is the diagnostic
      imaging of choice to exclude congenital tumours, lymphadenitis, congenital
      malformations of the Wharton's duct or the gland itself, and subcutaneous fat
      necrosis. CONCLUSION: Early diagnosis and antibiotic treatment of suppurative
      submandibular sialadenitis may prevent complications such as abscess formation,
      septicaemia and respiratory failure.

PMID- 14971807
TI  - Infection-induced wheezing during the first year of life does not mean asthma: a
      50-year-old observation.

PMID- 14971808
TI  - Upper gastrointestinal complications related to non-steroidal anti-inflammatory
      drugs--what have we achieved so far?

PMID- 14971809
TI  - Conservative approach to severe ulcerative colitis.

PMID- 14971810
TI  - Empirical Helicobacter pylori "rescue" therapy after failure of two eradication
      treatments.
AB  - AIM: Even with the current most effective Helicobacter pylori treatment regimens,
      approximately 20% of patients do not eradicate the infection. Several "rescue"
      therapies have been recommended, but they still fail to eradicate H. pylori in
      approximately 20-30% of the cases. Our aim was to evaluate the efficacy of
      different rescue therapies prescribed to patients in whom two consecutive H.
      pylori eradication regimens had failed. METHODS: Design. Prospective single
      centre study. Patients. Consecutive patients in whom two eradication regimens had
      failed to eradicate H. pylori. Intervention. Third eradication regimens included:
      (1) omeprazole-amoxicillin-clarithromycin for 7 days; (2) quadruple therapy with
      omeprazole-bismuth-tetracycline-metronidazole for 7 days; (3) omeprazole
      amoxicillin-clarithromycin-bismuth for 14 days; and (4) omeprazole-amoxicillin
      rifabutin for 14 days. H. pylori antibiotic susceptibility was unknown and,
      therefore, rescue regimens were chosen empirically. In no case, was the same
      regimen repeated. Outcome. H. pylori eradication was defined as a negative in 13C
      urea breath test 8 weeks after completing the therapy. RESULTS: Forty-eight
      patients were included (mean age 45 years, 44% males, 82% with peptic ulcer and
      18% with functional dyspepsia). No patient was lost from follow-up. Adverse
      effects were described in 21% of the patients. One patient receiving omeprazole,
      amoxicillin and rifabutin was removed from medication due to adverse effects
      (vomiting). Overall, mean H. pylori eradication with third therapy after failure
      of two eradication treatments was 34/48 (71%; 95% confidence interval 57-82%) by
      intention-to-treat and 34/47 (72%; 95% confidence interval 58-83%) by per
      protocol. CONCLUSION: It seems that performing culture even after a second
      eradication failure may not be necessary, as it is possible to construct an
      overall strategy to maximise H. pylori eradication, based on the different
      possibilities of empirical treatment.

PMID- 14971811
TI  - Bleeding duodenal ulcer: comparison between Helicobacter pylori positive and
      Helicobacter pylori negative bleeders.
AB  - BACKGROUND AND AIMS: To provide a direct comparison of Helicobacter pylori
      positive subjects bleeding from duodenal ulcer with H. pylori-negative ones, in
      terms of severity of bleeding and outcome. PATIENTS AND METHODS: A case-control
      study was prospectively conducted in 105 H. pylori-negative duodenal ulcer
      bleeders and same number of sex- and age-matched H. pylori-positive ones.
      RESULTS: NSAID consumption was more common among H. pylori-negative subjects
      (81%) compared to their H. pylori-positive counterparts (58.1%, P < 0.001). H.
      pylori-negative bleeders were found to need more often haemostasis (55.2% versus
      31.4%, P < 0.001) or surgical intervention (15.2% versus 4.8%, P = 0.011) and to
      have a greater proportion of rebleeding (32.4% versus 13.3%, P = 0.001), a more
      prolonged hospitalisation (11.6 +/- 4.1 versus 6.2 +/- 1.5 days, P < 0.001) and a
      higher rate of in-hospital mortality (15.2% versus 3.8%, P = 0.005). In the
      overall population (N = 210), H. pylori negativity, among other known risk
      factors, emerged as independent predictor (odds ratio: 3.2; 95% CI: 1.5, 11.2; P
      = 0.004) of an unfavourable outcome (surgery or death). CONCLUSIONS: Duodenal
      ulcer bleeding in H. pylori-negative subjects appears to be more severe, to have
      a higher rate of rebleeding, and to lead more often to surgery or fatality
      compared to the vast majority of H. pylori-positive duodenal ulcer bleeders.

PMID- 14971812
TI  - Outcome of a conservative approach in severe ulcerative colitis.
AB  - BACKGROUND: Severe ulcerative colitis is potentially life threatening even though
      a policy of intensive medical management and early colectomy in recent years
      reduced mortality to almost zero. However, colectomy, with or without ileal-anal
      anastomosis, has its own problems (morbidity, pouchitis, cuffitis) and no
      reliable prognostic index of surgical outcome has been developed. Intravenous
      steroids are still the mainstay of medical therapy but their maximal duration
      before stating a 'treatment failure' has not been defined. AIM OF THE STUDY: To
      evaluate the effectiveness, safety and outcome of an intensive medical approach
      in a series of patients with severe ulcerative colitis. PATIENTS AND METHODS: One
      hundred and forty-nine episodes of severe ulcerative colitis in 115 patients
      admitted to a Gastroenterology Unit in a 7-year period were retrospectively
      evaluated. Intravenous glucocorticosteroids--methylprednisolone 1 mg/kg/day--and
      topical steroids were administered, and supportive treatments with intensive
      monitoring were extended to all the patients. Second-line strategies for steroid
      refractoriness were prolonged glucocorticosteroids treatment, oral ciclosporin,
      infliximab or surgery. RESULTS: The median number of Truelove criteria at
      admission was 3 (range 2-5), median CRP 34 mg/l (range 10-196). Median follow-up
      after discharge was 49 months. In 84 (57%) episodes an early response was noted,
      while 65 (43%) did not respond within 10 days to the standard steroid treatment.
      In the non-responders group, 28 patients went into remission with a prolonged
      steroid treatment (slow responders); 15 patients were treated with ciclosporin
      (eight responders) and 6 with infliximab (four responders). A total of 24
      colectomies was performed in this group of patients (in 21 cases within 30 days
      from admission). Slow responders showed lower albumin levels (P = 0.02), higher
      cumulative dose of glucocorticosteroids in the year prior to admission (P = 0.02)
      and higher age (P = 0.03), in comparison with early responders. Major
      complications were noted in four episodes which responded to medical treatment.
      Disease-related mortality was zero. CONCLUSIONS: Medical treatment and use of
      second-line therapies were effective in the present series of patients. A group
      of slow responders has been identified and, if an intensive medical monitoring is
      guaranteed, steroids can be safely prolonged after the first 10 days of
      treatment. Cumulatively, about 80% of the patients responded to short-term
      medical treatment, only 5% of the patients underwent colectomy in the follow-up
      period. Major adverse events were recorded in four patients, who had recovered
      completely after adequate medical treatment.

PMID- 14971813
TI  - Genetic and serological markers to identify phenotypic subgroups in a Dutch
      Crohn' s disease population.
AB  - BACKGROUND AND AIMS: Both genetic and microbial factors seem to play a pivotal
      role in the aetiopathogenesis of Crohn's disease. The CARD15 frameshift mutation
      might link host genetic factors and the indigenous microbial flora, since CARD15
      expression is stimulated by peptidoglycan, thereby activating NF-kappaB. It is
      hypothesised that CARD15 mutation carriers have defective anti-microbial
      reactions, resulting in more penetrating lesions and antibody responses, which
      are now being used as highly specific markers for Crohn's disease. The
      serological marker anti-Saccharomyces cerevisiae antibody directed against cell
      wall oligomannosidic epitopes has high specificity for Crohn's disease.
      Perinuclear anti-neutrophil cytoplasmic antibodies have been found in a subgroup
      of Crohn's disease patients, mostly with colonic involvement. METHODS: We
      investigated the incidence of two CARD15 mutations (3020insC and 2722G>C), anti
      S. cerevisiae antibody, and perinuclear anti-neutrophil cytoplasmic antibody in
      108 (73F/35M) patients with Crohn's disease with a mean duration of disease since
      diagnosis of 16 (1-41) years in relation to their phenotype, according to the
      Vienna classification. RESULTS: The prevalence of CARD15 frameshift mutation was
      21%. Of all patients, 62% were anti-S. cerevisiae antibody positive, and 9% had
      perinuclear anti-neutrophil cytoplasmic antibodies. The prevalence of both anti
      S. cerevisiae antibodies and perinuclear anti-neutrophil cytoplasmic antibodies
      was higher in the mutation carriers compared to non-carriers. Remarkably, all
      patients with a CARD15 mutation and positive anti-S. cerevisiae antibody had
      ileal disease. Carriership of the mutation was significantly associated with
      penetrating behaviour of the disease and weakly associated with stricturing
      behaviour. Furthermore, anti-S. cerevisiae antibody was associated with ileal
      disease involvement. Finally, most perinuclear anti-neutrophil cytoplasmic
      antibody positive patients showed ulcerative-like behaviour of disease (by means
      of colonic localisation). CONCLUSIONS: Genetic and serologic markers might be
      useful in defining patient subgroups. This may result in a more accurate
      prediction of disease behaviour, prognosis and therapeutic approach.

PMID- 14971814
TI  - Ultrastructural mucosal alterations and increased intestinal permeability in non
      celiac, type I diabetic patients.
AB  - BACKGROUND: Increased intestinal permeability was described in several intestinal
      auto-immune conditions. There are very few and contradictory reports about type I
      diabetes mellitus, an auto-immune condition sometimes associated with celiac
      disease. AIMS: To investigate intestinal permeability in type I diabetes mellitus
      patients with no concomitant celiac disease, with a comparison to ultra
      structural aspects of duodenal mucosa. PATIENTS: 46 insulin dependent diabetes
      mellitus, non-celiac, patients (18 females and 28 males, mean age 15.8 +/- 5.3
      [S.D.] years) were enrolled. The mean duration of the disease was 5.7 years.
      METHODS: The morphological aspect of the small bowel mucosa, at standard light
      microscopy and electron transmission microscopy, along with intestinal
      permeability (by lactulose/mannitol test) were studied. Lactulose and mannitol
      urinary excretion were determined by means of high performance anion exchange
      chromatography-pulsed amperometric detection. RESULTS: The lactulose/mannitol
      ratio was 0.038 [0.005-0.176] (median and range) in 46 patients compared to 0.014
      [0.004-0.027] in 23 controls: insulin dependent diabetes mellitus group values
      being significantly higher than those of the controls (P < 0.0001, Mann-Whitney
      test). Eight insulin dependent diabetes mellitus patients underwent endoscopy and
      biopsies were analysed by means of light microscopy and transmission electron
      microscopy. At the light microscopy level, none of the biopsy samples showed any
      sign of atrophy nor inflammation, whereas transmission electron microscopy
      analysis showed remarkable ultra-structural changes in six out of the eight
      patients. Four parameters were evaluated: height and thickness of microvilli,
      space between microvilli and thickness of tight junctions. CONCLUSIONS: This
      alteration of intestinal barrier function in non-celiac type I diabetes mellitus,
      frequently associated with mucosal ultra-structural alterations, could suggest
      that a loss of intestinal barrier function can be a pathogenetic factor in a
      subset of insulin dependent diabetes mellitus patients.

PMID- 14971815
TI  - Survival rate and prognostic factors in patients with intestinal failure.
AB  - BACKGROUND: Intestinal failure impairs nutritional status and survival
      expectance. Though intestinal adaptation and enteral independence may be
      achieved, artificial nutrition is needed in about half of the patients. AIMS:
      This study is aimed at assessing the causes of death, survival rate, enteral
      independence in time, and factors affecting the clinical outcome in a group of
      patients with intestinal insufficiency. PATIENTS: Sixty-eight patients with
      intestinal insufficiency, due to major intestinal resection in 60 cases (short
      bowel syndrome) (remnant intestine length 101-150 cm in 31 cases, 50-100 cm in 23
      cases, <50 cm in 6 cases), and due to chronic idiopathic pseudo-obstruction in 8
      cases, were enrolled and followed-up for (median) 36 months (25th and 75th
      percentile in 12 and 60 months, respectively). In 60 short bowel syndrome
      patients, the main conditions that led to intestinal failure were ischemic bowel
      (28), major surgery complications or severe adhesions (17), radiation enteritis
      (10), Chron's disease, intestinal tuberculosis, small bowel lymphoma and trauma
      (others). METHODS: Seventeen variables age, underlying disorders, length of
      remnant bowel, type of surgery, hospital stay, type of nutrition (hospital and
      home) and its variations in time, causes of death, survival rate and time were
      considered. Statistical analysis was carried out by Mann-Whitney U-test, Pearson
      chi2, Spearman correlation test, Kaplan-Meyer method and Cox's proportion hazards
      regression model. RESULTS: At the time of admission to the hospital, none of the
      patients had nutritional independence, 54 (79.4%) were on parenteral nutrition
      and 14 (20.6%) were on enteral nutrition. At the time of discharge, 23 (33.8%)
      patients showed enteral independence, 39 were on home parenteral nutrition, 3 on
      enteral nutrition + i.v. feeding, 1 on enteral nutrition, and 2 needed oral
      supplementation with hydroelectrolyte solutions only. After a median value of 36
      months, 30 and 2 patients were on home parenteral nutrition and enteral nutrition
      + i.v. feeding, respectively, 2 on enteral nutrition, 2 on oral supplementation
      with hydroelectrolyte solutions, and 26 cases reached enteral independence. A
      significant relationship was detected between the length of remnant bowel and
      types of nutrition at both admission (r = 0.38; P = 0.001) and discharge (r =
      0.48; P = 0.001), parenteral nutrition being more frequent in patients with very
      short bowel. Twenty-two patients (32.4%) died (4 from newly occurring
      malignancies), 40 (58.8%) survived, and 6 (8.8%) were lost to the follow-up.
      Eleven of 22 patients died from conditions related to intestinal failure (8
      cases) and/or home parenteral nutrition complications (3 cases). At 12, 24, 36,
      48, 60 and 72 months, survival rates were 95.4, 93.3, 88.1, 78.6, 78.6 and 65.5%,
      respectively, but it was significantly lower for patients with <50 cm of remnant
      bowel than those with longer residual intestine (P < 0.05), and in patients who
      started home parenteral nutrition above the age of 45 years (P < 0.02). Survival
      rate was higher in patients with enteral independence than those with enteral
      dependence (P < 0.05). Better survival rates were registered in patients with
      chronic obstructive intestinal pseudo-obstruction and major surgery
      complications, whereas ischemic bowel and even more radiation enteritis were
      associated with a lower survival expectance. CONCLUSIONS: Actuarial survival rate
      of patients with intestinal failure quotes 88 and 78% at 3 and 5 years,
      respectively. It is influenced by the length of remnant intestine, age at the
      start of home parenteral nutrition, enteral independence and, to some extent at
      least, by the primary disorder. Enteral independence can be achieved in time by
      about 40% of the patients with intestinal insufficiency, but for home parenteral
      nutrition-dependent cases, intravenous feeding can be stopped in less than one
      out of five patients during a median 3-year period.

PMID- 14971816
TI  - Characteristics of liver cirrhosis in Italy: results from a multicenter national
      study.
AB  - BACKGROUND: In 1992, the characteristics of liver cirrhosis in Italy were
      assessed in a cross-sectional study among 1829 cirrhosis patients attending 21
      tertiary centres. AIM: To evaluate the characteristics of cirrhosis patients 9
      years later. PATIENTS: A total of 2185 consecutive cirrhosis patients were
      enrolled over a 6-month period in 79 hospitals located throughout Italy, randomly
      selected by means of systematic cluster sampling. RESULTS: The main agent
      associated with cirrhosis was hepatitis C virus, which was found in 69.9% of the
      patients and was the only etiologic factor in 51.1% of the patients. Hepatitis B
      surface antigen was present in the serum of 13.0% of the cases (in 7.3%, it was
      the only etiologic factor). A history of alcohol abuse was found in 31.9% of the
      cases (12.4% without viral infection). Patients with hepatitis C virus-related
      cirrhosis were older (mean age of 64.4 years) and more likely to be female
      (male:female ratio of 0.7), compared to patients with other pathogenic factors.
      Virus-related cirrhosis was more likely to be observed in southern Italy, whereas
      alcohol-related cirrhosis was prevalent in the North. CONCLUSIONS: As found in
      the 1992 study, the results of the present study show that in Italy, liver
      cirrhosis is mainly associated with hepatitis C virus infection, reflecting the
      high prevalence of this infection in the general population.

PMID- 14971817
TI  - Chronic pancreatitis: relation between function and morphology.
AB  - BACKGROUND: In our department, we routinely use a combined exocrine-endocrine
      function test to evaluate the pancreatic function in chronic pancreatitis i.e.
      urinary para amino benzoic acid (PABA) recovery and pancreatic polypeptide
      secretion in response to a meal and glucose tolerance test. AIM: To study the
      relationship between changes in morphology and exocrine/endocrine function in
      patients with chronic pancreatitis. PATIENTS AND METHODS: In 103 patients with
      chronic pancreatitis seen by our department for evaluation of pancreatic function
      between 1989 and 1999, we retrospectively analysed the correlation between
      morphology (Cambridge-score) and function. Furthermore the differences in
      presentation, function and morphology between patients with alcohol-induced
      chronic pancreatitis and idiopathic chronic pancreatitis were evaluated. RESULTS:
      Significant correlation were found for both PABA recovery and pancreatic
      polypeptide secretion with morphologic score, respectively r = -0.205 (P = 0.037)
      and r = -0.209 (P = 0.031), but not with endocrine function. The correlation
      between morphology and PABA recovery or pancreatic polypeptide secretion was
      observed in the subgroup with alcohol-induced chronic pancreatitis but not in
      those with idiopathic chronic pancreatitis. Pain is a prominent symptom of
      chronic pancreatitis. Pain was more frequent and more severe in patients
      suffering from chronic pancreatitis caused by alcohol or idiopathy. CONCLUSIONS:
      Morphology and exocrine function correlate in patients with alcohol-induced
      chronic pancreatitis but not in patients with chronic pancreatitis. When compared
      to patients with chronic pancreatitis of idiopathic origin, patients with
      alcoholic origin show differences in presentation and morphology but not in
      function.

PMID- 14971818
TI  - Endoscopic balloon dilatation is a safe method in the management of common bile
      duct stones.
AB  - BACKGROUNDS AND AIMS: Endoscopic sphincterotomy is a widely accepted treatment
      for patients with common bile duct stones. Despite improvement in this technique,
      endoscopic sphincterotomy is still associated with some biliary complications.
      Endoscopic balloon dilatation is a less traumatic and sphincter preserving method
      for removal of common bile duct stones. However, the results of controlled
      studies in comparison with these two methods are contradictory. The aim of this
      study is to compare the safety and efficacy of endoscopic balloon dilatation and
      endoscopic sphincterotomy in Chinese patients. PATIENTS AND METHODS: A total of
      104 patients with common bile duct stones on endoscopic retrograde
      cholangiopancreatography were enrolled. They were randomly assigned to endoscopic
      balloon dilatation or endoscopic sphincterotomy. Endoscopic balloon dilatation
      was performed by using a balloon dilator to dilate the sphincter for 5 min. The
      common bile duct stones were then removed by a Dormia basket after endoscopic
      balloon dilatation or endoscopic sphincterotomy. Mechanical lithotripsy was
      performed if the stones were difficult to remove by Dormia basket. After
      discharge, patients were regularly followed up for biliary complications.
      RESULTS: The successful bile duct stone clearance rate was 94.1% in endoscopic
      balloon dilatation group and 100% in endoscopic sphincterotomy group. Post
      procedural significant haemorrhage was higher in endoscopic sphincterotomy group
      than in endoscopic balloon dilatation group (14/53 versus 1/48, P < 0.001). The
      bleeding patient from endoscopic balloon dilatation group was a case of uremia
      and bleeding occurred 48 h after endoscopic balloon dilatation. All the patients
      with post-procedural haemorrhage were controlled endoscopically. The post
      procedural serum amylase level showed no significant difference in both groups
      and none of them developed clinical pancreatitis. After a mean 16 months follow
      up, three patients (6.3%) in endoscopic balloon dilatation group and four
      patients (7.5%) in endoscopic sphincterotomy group developed recurrent common
      bile duct stones. The recurrent common bile duct stones were multiple and muddy
      in consistency. They were successfully removed endoscopically. CONCLUSION: Both
      endoscopic balloon dilatation and endoscopic sphincterotomy are safe and
      effective techniques for the treatment of common bile duct stones. Endoscopic
      balloon dilatation can be safely applied in patients with coagulopathy and does
      not increase the incidence of pancreatitis or bleeding.

PMID- 14971819
TI  - Pre-operative endoscopic ultrasonography can optimise the management of patients
      undergoing laparoscopic cholecystectomy with abnormal liver function tests as the
      sole risk factor for choledocholithiasis: a prospective study.
AB  - BACKGROUND: Pre-operative endosonography has been proposed as a cost-effective
      procedure in the management of patients who undergo laparoscopic cholecystectomy
      having an intermediate risk of common bile duct stones. We prospectively
      evaluated the impact of pre-operative endosonography on the management of
      patients facing laparoscopic cholecystectomy with abnormal liver function tests
      as the sole risk factor for choledocolithiasis. METHODS: Among 587 consecutive
      patients scheduled for laparoscopic cholecystectomy, 47 (8%) patients having one
      or more abnormal liver function tests but a normal appearance of common bile duct
      at abdominal ultrasound, underwent pre-operative endosonography. In patients with
      endosonography-detected common bile duct stones, a pre-operative endoscopic
      retrograde cholangiography was performed, or an intra-operative endoscopic
      retrograde cholangiography was scheduled. In all endosonography-negative
      patients, an intra-operative trans-cystic cholangiography was performed. RESULTS:
      Endosonography detected common bile duct stones in nine patients (19%) but only
      in five of them stones were radiologically confirmed (PPV 0.55). Endosonography
      detected stones were confirmed in four of four (100%) patients in whom
      cholangiography was performed within 1 week, but only in one of five (20%)
      patients in whom radiology was further delayed (P < 0.05). In three of four cases
      (75%), stones detected at endosonography but not confirmed at X-rays, were
      smaller than 2.0 mm. Among 38 patients with negative endosonography, common bile
      duct stones were found in two patients (NPV 0.95), whereas unplanned endoscopic
      stone extraction was needed only in one patient (NPV 0.97). CONCLUSIONS: Pre
      operative endosonography can spare unnecessary pre-operative endoscopic
      retrograde cholangiography as well as inappropriate scheduling of intra-operative
      endoscopic retrograde cholangiography in patients undergoing laparoscopic
      cholecystectomy with abnormal liver function tests. To maximise the impact of
      endosonography on the management of these patients, the procedure should be
      performed immediately before laparoscopic cholecystectomy.

PMID- 14971820
TI  - Symptomatic reversible duodenal compression due to iatrogenic retroperitoneal
      hematoma.
AB  - Selective serotonin reuptake inhibitors are frequently employed to treat
      depression. However, although rarely, coagulation abnormalities have been
      described following the use of these compounds, and these effects appear to be
      enhanced by simultaneous use of nonsteroidal anti-inflammatory drugs. We describe
      a case of reversible symptomatic duodenal compression caused by a retroperitoneal
      hematoma after ingestion of sertraline and nimesulide.

PMID- 14971821
TI  - Leflunomide-induced acute hepatitis.
AB  - Leflunomide, a new immunomodulatory agent, was prescribed to a 67-year-old female
      patient with rheumatoid arthritis. Fifteen days later she developed diarrhoea and
      elevated liver enzymes. A liver biopsy showed a pattern of acute hepatitis. The
      patient was homozygous for the rare CYP2C9*3 allele, which determines the slowest
      metabolic rate for CYP2C9 enzymatic activity, that is probably involved in the
      metabolism of leflunomide. Liver damage subsided in few weeks. This case
      illustrates the risk of hepatotoxicity by leflunomide and suggests that it is
      possibly related to CYP2C9 polymorphism.

PMID- 14971822
TI  - Triptans and gastric accommodation: pharmacological and therapeutic aspects.
AB  - In the past decade, several studies have reported a significant delay of gastric
      emptying induced by the anti-migraine agent sumatriptan (a 5-hydroxytryptamine (5
      HT)1B/D receptor agonist) in healthy human beings. In patients with functional
      dyspepsia, sumatriptan improves gastric accommodation after food consumption and
      reduce perception of gastric distension, hence relieving epigastric symptoms.
      Recent studies have established that impaired accommodation after food
      consumption is a major patho-physiological mechanism in functional dyspepsia and
      restoration of accommodation is considered to be a potential therapeutic target.
      The precise site of action of sumatriptan in humans is at present unknown,
      although recent studies carried out using a canine model indicate that
      sumatriptan exerts its action on gastric accommodation through 5-HT1B receptors,
      since both GR127935 and SB216641 (respectively, non selective 5-HT1B/D and
      selective 5-HT1B receptor antagonists) fully antagonised the effects of
      sumatriptan. Gastric relaxation and enhanced accommodation to a distending
      stimulus seem to be a class effect of triptans, since it occurs not only with
      sumatriptan, but also with second-generation triptans (rizatriptan and
      naratriptan), at least in a canine model. In dyspeptic patients, administration
      of triptans would be able to restore gastric accommodation after a meal and to
      improve symptoms of early satiety, confirming the therapeutic potential of 5
      HT1B/D receptor agonists in functional dyspepsia.

PMID- 14971823
TI  - Recent data on the development of cloned embryos derived from reconstructed eggs
      with adult cells.
AB  - Production of cloned embryos by nuclear transfer from adult somatic cells is a
      novel and promising technique in animal biotechnology. In spite of numerous
      reported viable offspring in various species, the efficiency of the technique
      remains very low. Embryonic and fetal mortality occurs all along pregnancy and
      during the peri-natal life, even months after birth. Both embryonic and placental
      dysfunctions might be involved. However the precise causes of such developmental
      failures are still unknown. In the present review, we report data from different
      studies which described the main defaults which have been observed after
      embryonic cloning in various species. The putative molecular and cellular causes
      of these developmental failures are discussed.

PMID- 14971824
TI  - Cryopreservation of bovine oocytes: current status and recent developments.
AB  - The cryopreservation of oocytes of most animal species remains a challenge due to
      their complex structure. Equilibrium freezing is not satisfactory because oocytes
      seem to be damaged by exposure for several minutes to temperatures near 0 degrees
      C. Therefore, cryopreservation of oocytes by vitrification--especially the use of
      very high cooling rates of oocytes suspended in extremely small volumes of
      various cryoprotective additive modifications--seems the most appropriate method.

PMID- 14971825
TI  - Effect of diets rich in N-3 polyunsatured fatty acids on muscle lipids and fatty
      acids in Belgian Blue double-muscled young bulls.
AB  - The present study was aimed at investigating the effect of duration and time of
      feeding n-3 fatty acids on the fatty acid composition of intramuscular fat and
      adipose tissue of bulls at slaughter. Four groups of bulls were given during
      three periods different diets, mainly differing in the presence of linseed as the
      predominant n-3 fatty acid source in the concentrate either or not in combination
      with grass (silage) as the roughage. The results show that the fatty acid
      composition of the feed during the earlier periods of life of the animal were
      important and influenced the final intramuscular fatty acid composition. Feeding
      n-3 PUFA during the phases before the finishing diet increased the long chain n-3
      PUFA (C20:5n-3, C22:5n-3 and C22:6n-3) compared to animals which were fed only a
      C 18:3n-3 rich concentrate in the finishing period. The cis-9,trans-11CLA content
      was increased by feeding linseed in the fattening period and was mainly deposited
      in the triacylglycerol fraction of the intramuscular fat.

PMID- 14971826
TI  - Fructooligosaccharide associated with celecoxib reduces the number of aberrant
      crypt foci in the colon of rats.
AB  - According to Burkitt's hypothesis, dietary fibres may protect against the
      development of colorectal cancer. In rats, studies have shown that only butyrate
      producing fibres are protective. In parallel, in humans, non-steroidal anti
      inflammatory drugs, which target cyclooxygenases, have been shown to display a
      protective effect against colorectal cancer. Among them, COX-2-selective
      inhibitors which present less side effects than non-selective agents, are
      promising as chemopreventive agents. Our aim was to analyse the effect of an
      association between butyrate-producing fibres and the COX-2 inhibitor on the
      development of aberrant crypt foci (ACF) in rats. Fisher F344 rats were fed with
      (1) a standard low fibre control diet; (2) the standard diet supplemented with
      1500 ppm celecoxib; (3) a diet supplemented with 6% fructo-oligosaccharide (FOS);
      and (4) a diet with both celecoxib and FOS. Three weeks later, the rats were
      injected twice with azoxymethane and the number of ACF was determined 15 weeks
      later. In the control group, 43.8 +/- 6.4 ACF were found. This number was not
      significantly modified by the addition of FOS or celecoxib alone to the diet.
      However, the association of FOS and celecoxib resulted in a 61% reduction in the
      number of ACF (P < 0.01). The number of aberrant crypt per foci was also reduced.
      Thus, although no significant effect of celecoxib or FOS alone was identified,
      the association of butyrate-producing fibre and celecoxib was effective in
      preventing the development of ACF. This preliminary study argues for a strong
      protective effect of such an association which deserves further studies.

PMID- 14971827
TI  - Propionate supplementation did not increase whole body glucose turnover in
      growing lambs fed rye grass.
AB  - The objective of the present study was to investigate the effects of propionate
      supplementation on whole body glucose turnover in growing lambs fed frozen rye
      grass at 1.5 x maintenance using [1-13C]-glucose. Intraruminal infusion of
      propionate (0.55 and 0.91 mol x d(-1)) increased the ruminal molar proportions of
      propionate from 25% with the control to 40% with the highest propionate
      treatment. It did not however modify glucose turnover (26 mmol x d(-1) x kg(-1)),
      nor the conversion of its carbon into L-lactate (21%) and alanine (21%), nor
      glucose recycling (9%). All of the results suggest that in the present conditions
      glucose turnover and metabolism were not influenced by the supply of propionate.

PMID- 14971828
TI  - Whole body glucose turnover in growing and non-productive adult ruminants: meta
      analysis and review.
AB  - The objectives of the present paper were to review and quantitatively determine
      the influence of the nutritional factors on whole body glucose turnover in
      growing and adult non-productive ruminants. A meta-analysis approach was used.
      The dietary grain: forage ratio significantly increased the slope of the
      relationship between glucose turnover and metabolisable energy intake. This
      effect was probably associated with the inclusion of maize rather than any other
      grain source in the diet. The analysis pointed out the possible differences in
      response between growing and adult non-productive animals, and suggested that the
      performance level of the animals (and their glucose requirements) could
      contribute to regulating whole body glucose turnover. This aspect would warrant
      further investigation.

PMID- 14971829
TI  - Urinary selenium excretion in selenite-loaded sheep and subsequent Se dynamics in
      blood constituents.
AB  - Renal selenium excretion in sheep was measured during intravenous infusion of
      sodium selenite, and the post-infusion dynamics of Se levels in whole blood,
      plasma and red blood cells (RBC) were investigated for the next 5 days. The
      plasma Se level increased almost twenty fold with the infusion of Na2SeO3 (from
      0.39 +/- 0.02 to 7.83 +/- 0.33 micromol x L(-1), P < 0.001) compared with the
      baseline value. The selenium concentration in urine (0.07 +/- 0.02 vs. 18.53 +/-
      2.56 micromol x L(-1), P < 0.001), the amount of Se excreted (0.14 +/- 0.07 vs.
      21.40 +/- 2.31 nmol x min(-1), P < 0.001) and the renal clearance of Se (0.1 9 +/
      0.03 vs. 3.01 +/- 0.34 mL x min(-1), P < 0.001) were found to be highly
      significantly elevated during selenite loading. The clearance measurements showed
      no changes in the urinary flow rate or in the glomerular filtration rate. During
      and at the end of infusion the highest Se level was attained in plasma, followed
      by whole blood and RBC. The plasma Se level fell rapidly within 10 min after the
      end of infusion, but the concentration of Se in RBC was stable up to the fourth
      hour, when it started to decrease too. On day 5 the Se concentrations in plasma,
      RBC and whole blood were found to be only slightly but still significantly higher
      than before the selenite infusion. The large disproportion between the infusion
      rate of Se (8.76 microg x min(-1)) and its renal excretion rate (1.69 microg x
      min(-1)) found in clearance measurements suggests low glomerular filtration of
      infused selenium, which might primarily be caused by the binding of selenite
      metabolites to blood constituents. The presented results confirm the low
      bioavailability to ruminants of Se from sodium selenite.

PMID- 14971830
TI  - Possible drug interactions among quinolones.

PMID- 14971831
TI  - Herbal products should be regulated for quality control.

PMID- 14971832
TI  - Mefloquine for preventing malaria in nonimmune adult travelers.

PMID- 14971833
TI  - Management of peripheral arterial disease.
AB  - Peripheral arterial disease is common, but the diagnosis frequently is overlooked
      because of subtle physical findings and lack of classic symptoms. Screening based
      on the ankle brachial index using Doppler ultrasonography may be more useful than
      physical examination alone. Noninvasive modalities to locate lesions include
      magnetic resonance angiography, duplex scanning, and hemodynamic localization.
      Major risk factors for peripheral arterial disease are cigarette smoking,
      diabetes mellitus, older age (older than 40 years), hypertension, hyperlipidemia,
      and hyperhomocystinemia. Nonsurgical therapy for intermittent claudication
      involves risk-factor modification, exercise, and pharmacologic therapy. Based on
      available evidence, a supervised exercise program is the most effective
      treatment. All patients with peripheral arterial disease should undergo
      aggressive control of blood pressure, sugar intake, and lipid levels. All
      available strategies to help patients quit smoking, such as counseling and
      nicotine replacement, should be used. Effective drug therapies for peripheral
      arterial disease include aspirin (with or without dipyridamole), clopidogrel,
      cilostazol, and pentoxifylline.

PMID- 14971834
TI  - Information from your family doctor. Peripheral arterial disease.

PMID- 14971835
TI  - Viral croup.
AB  - Viral croup is the most common form of airway obstruction in children six months
      to six years of age. The frightening nature of croup often prompts parents and
      caregivers to seek physician consultation. For children with mild croup,
      symptomatic care and mist therapy may be all that is necessary. Epinephrine has
      been used for decades to treat more severe cases of croup, but recent meta
      analyses have found that glucocorticoid use is associated with shorter hospital
      stays, improvement in croup scores, and less use of epinephrine. Studies have
      shown that treatment with 0.6 mg per kg of oral dexamethasone is as effective as
      intramuscular dexamethasone or 2 mg of nebulized budesonide. Oral dexamethasone
      in dosages as low as 0.15 mg per kg also may be effective. While more studies are
      needed to establish guidelines, oral dexamethasone can be used to treat mild to
      moderate croup with close follow-up and instructions for further care, if needed.

PMID- 14971836
TI  - Information from your family doctor. What should I know about croup?

PMID- 14971837
TI  - Strength of recommendation taxonomy (SORT): a patient-centered approach to
      grading evidence in the medical literature.
AB  - A large number of taxonomies are used to rate the quality of an individual study
      and the strength of a recommendation based on a body of evidence. We have
      developed a new grading scale that will be used by several family medicine and
      primary care journals (required or optional), with the goal of allowing readers
      to learn one taxonomy that will apply to many sources of evidence. Our scale is
      called the Strength of Recommendation Taxonomy. It addresses the quality,
      quantity, and consistency of evidence and allows authors to rate individual
      studies or bodies of evidence. The taxonomy is built around the information
      mastery framework, which emphasizes the use of patient-oriented outcomes that
      measure changes in morbidity or mortality. An A-level recommendation is based on
      consistent and good-quality patient-oriented evidence; a B-level recommendation
      is based on inconsistent or limited-quality patient-oriented evidence; and a C
      level recommendation is based on consensus, usual practice, opinion, disease
      oriented evidence, or case series for studies of diagnosis, treatment,
      prevention, or screening. Levels of evidence from 1 to 3 for individual studies
      also are defined. We hope that consistent use of this taxonomy will improve the
      ability of authors and readers to communicate about the translation of research
      into practice.

PMID- 14971838
TI  - Treatment of obstructive sleep apnea in primary care.
AB  - Obstructive sleep apnea should be suspected in patients who are overweight snore
      loudly, and have chronic daytime sleepiness. The diagnosis of sleep apnea may be
      confirmed by sleep laboratory studies. Patients' symptoms and the frequency of
      respiratory events on laboratory testing are important factors in determining the
      severity of disease. In patients with mild sleep apnea, conservative treatment
      measures include getting sufficient sleep, abstaining from the use of alcohol and
      sedatives, losing weight, and avoiding the supine position during sleep.
      Continuous positive airway pressure (CPAP) is the most consistently effective
      treatment for clinically significant obstructive sleep apnea. In general, heavier
      patients with thicker necks require higher pressure settings. As patients age or
      gain weight, additional pressure may be necessary. Bilevel pressure machines or
      machines that slowly ramp up the pressure may increase patient acceptance of CPAP
      therapy. Complications of CPAP use include nasal dryness and congestion,
      claustrophobia, facial skin abrasions, air leaks, and conjunctivitis. Strategies
      to improve patient compliance include allowing patients to try a number of masks
      to find the most comfortable fit, adding humidification, treating nasal disease
      and, most importantly, providing close follow-up and encouragement. Oral
      appliances are inconsistently effective in the management of obstructive sleep
      apnea but may be an option in patients with mild disease who cannot tolerate
      CPAP. Palatal surgery often decreases snoring but may not reduce the occurrence
      of sleep apnea. Patients with severe disease and intolerance of CPAP may be
      candidates for more invasive surgical procedures. Supplemental oxygen and drug
      therapy may have limited, adjunctive roles in the treatment of obstructive sleep
      apnea.

PMID- 14971839
TI  - Information from your family doctor. CPAP for sleep apnea.

PMID- 14971840
TI  - Regional anesthesia for office procedures: part I. Head and neck surgeries.
AB  - Although local anesthesia usually is used in surgical procedures, field or nerve
      blocks can provide more effective anesthesia in some situations. In a field
      block, local anesthetic is infiltrated around the border of the surgical field,
      leaving the operative area undisturbed. In field blocks, epinephrine may be added
      to the anesthetic to enhance vasoconstriction and prolong the duration of
      anesthesia. In a nerve block, anesthetic is injected directly adjacent to the
      nerve supplying the surgical field. A review of regional anatomy and the location
      of nerves and other important structures is essential before administering the
      injection. Systemic toxicity is rare with regional anesthesia and can be
      prevented by using the smallest dose possible and aspirating before the
      injection. Supraorbital, supratrochlear, infraorbital, and mental nerve blocks
      can provide adequate anesthesia in procedures on parts of the face. Field block
      also may be considered when operating on the ear or lips.

PMID- 14971841
TI  - Tinnitus.

PMID- 14971842
TI  - Are selective COX-2 inhibitors as effective as NSAIDs in patients with rheumatoid
      arthritis?

PMID- 14971843
TI  - Suspected pulmonary embolism: evidence-based diagnostic testing.

PMID- 14971844
TI  - Screening for type 2 diabetes mellitus in adults.

PMID- 14971845
TI  - A case of necrotic toes.

PMID- 14971847
TI  - Information from your family doctor. Penile cancer.

PMID- 14971846
TI  - Information from your family doctor. Testicular cancer.

PMID- 14971848
TI  - Information from your family doctor. Prostate cancer.

PMID- 14971849
TI  - ACOG releases guidelines for prophylactic antibiotic use in labor and delivery.

PMID- 14971850
TI  - AAP releases policy statement on poison treatment in the home.

PMID- 14971851
TI  - A one-stop health care request.

PMID- 14971852
TI  - Effects of fungal bioaugmentation and cyclodextrin amendment on fluorene
      degradation in soil slurry.
AB  - This study assesses the potential of fungal bioaugmentation and the effect of
      maltosyl-cyclodextrin amendment, as an approach to accelerate fluorene
      biodegradation in soil slurries. 47 fungal strains isolated from a contaminated
      site were tested in the biodegradation of fluorene. Results showed the greater
      efficiency of "adaptated" fungi isolated from contaminated soil vs. reference
      strains belonging to the collection of the laboratory. These assays allowed us to
      select the most efficient strain, Absidia cylindrospora, which was used in a
      bioaugmentation process. In the presence of Absidia cylindrospora, more than 90%
      of the fluorene was removed in 288 h while 576 h were necessary in the absence of
      fungal bioaugmentation. Maltosyl-cyclodextrin, a branched-cyclodextrin was chosen
      in order to optimize fluorene bioavailability and biodegradation in soil
      slurries. The results of this study indicate that Absidia cylindrospora and
      maltosyl-cyclodextrin could be used successfully in bioremediation systems.

PMID- 14971853
TI  - Degradation of the radioactive and non-labelled branched 4(3',5'-dimethyl 3'
      heptyl)-phenol nonylphenol isomer by sphingomonas TTNP3.
AB  - The degradation of the 4(3',5'-dimethyl-3'-heptyl)-phenol (p353NP) nonylphenol
      isomer in cultures of Sphingomonas TTNP3 supplemented with the technical mixture
      of nonylphenol was first assessed. Then the radioactive and non-labelled form of
      these diastereomers were both synthesised. The radioactive isomers were
      synthesised using [ring-U-14C]-labelled phenol and 3,5-dimethyl-3-heptanol by
      Friedel and Crafts alkylation. The time-course of degradation was performed with
      and without 14C-p353NP; balancing of radioactivity was calculated from different
      soluble fractions (organic, aqueous), bacterial biomass, and 14CO2 evolved as
      mineralization product. The noticeable portion of 14C bound to biomass showed
      that at least the aromatic ring of 14C-p353NP was degraded and served as energy
      source and probably as carbon source for bacterial growth. In addition, the
      appearance of 3,5-dimethyl-3-heptanol, the nonanol corresponding with the side
      chain of p353NP, was demonstrated in the bacterial media, and its concentration
      determined during the course of fermentation. Besides the parent 14C-p353NP, no
      other radioactive compounds, i.e. metabolites of 14C-p353NP were detected in the
      media.

PMID- 14971854
TI  - Trichloroethylene degradation by toluene-oxidizing bacteria grown on non-aromatic
      substrates.
AB  - The potential of trichloroethylene (TCE) to induce and non-aromatic growth
      substrates to support TCE degradation in five strains (Pseudomonas mendocina KR1,
      Ralstonia pickettii PKO1, Pseudomonas putida F1, Burkholderia cepacia G4, B.
      cepacia PR1) of toluene-oxidizing bacteria was examined. LB broth and acetate did
      not support TCE degradation in any of the wild-type strains. In contrast,
      fructose supported the highest specific levels of TCE oxidation observed in each
      of the strains tested, except B. cepacia G4. We discuss the potential mechanisms
      and implications of this observation. In particular, cells of P. mendocina KR1
      degraded significant amounts of TCE during cell growth on non-aromatic
      substrates. Apparently, TCE degradation was not completely constrained by any
      given factor in this microorganism, as was observed with P. putida F1 (TCE was an
      extremely poor substrate) or B. cepacia G4 (lack of oxygenase induction by TCE).
      Our results indicate that multiple physiological traits are required to enable
      useful TCE degradation by toluene-oxidizing bacteria in the absence of aromatic
      cosubstrates. These traits include oxygenase induction, effective TCE turnover,
      and some level of resistance to TCE mediated toxicity.

PMID- 14971855
TI  - Potential for aerobic and anaerobic biodegradation of petroleum hydrocarbons in
      boreal subsurface.
AB  - We studied the role of aerobic and anaerobic petroleum hydrocarbon degradation at
      a boreal, light-weight fuel and lubrication oil contaminated site undergoing
      natural attenuation. At the site, anoxic conditions prevailed with high
      concentrations of CH4 (up to 25% v/v) and CO2 (up to 18% v/v) in the soil gas
      throughout the year. Subsurface samples were obtained mainly from the anoxic
      parts of the site and they represented both the unsaturated and saturated zone.
      The samples were incubated in microcosms at near in situ conditions (i.e. in situ
      temperature 8 degrees C, aerobic and anaerobic conditions, no nutrient
      amendments) resulting in the removal of mineral oil (as determined by gas
      chromatography) aerobically as well as anaerobically. In the aerobic microcosms
      on average 31% and 27% of the initial mineral oil was removed during a 3- and 4
      month incubation, respectively. In the anaerobic microcosms, on average 44% and
      15% of the initial mineral oil was removed during a 12- and 10-month anaerobic
      incubation, respectively, and e.g. n-alkanes from C11 to C15 were removed. A
      methane production rate of up to 2.5 microg CH4 h(-1) g(-1) dwt was recorded in
      these microcosms. In the aerobic as well as anaerobic microcosms, typically 90%
      of the mineral oil degraded belonged to the mineral oil fraction that eluted from
      the gas chromatograph after C10 and before C15, while 10% belonged to the
      fraction that eluted after C15 and before C40. Our results suggest that anaerobic
      petroleum hydrocarbon degradation, including n-alkane degradation, under
      methanogenic conditions plays a significant role in the natural attenuation in
      boreal conditions.

PMID- 14971856
TI  - Detection and decontamination of residual energetics from ordnance and explosives
      scrap.
AB  - Extensive manufacturing of explosives in the last century has resulted in
      widespread contamination of soils and waters. Decommissioning and cleanup of
      these materials has also led to concerns about the explosive hazards associated
      with residual energetics still present on the surfaces of ordnance and explosives
      scrap. Typically, open burning or detonation is used to decontaminate ordinance
      and explosive scrap. Here the use of an anaerobic microbiological system applied
      as a bioslurry to decontaminate energetics from the surfaces of metal scrap is
      described. Decontamination of model metal scrap artificially contaminated with
      2,4,6-trinitrotoluene and of decommissioned mortar rounds still containing
      explosives residue was examined. A portable ion mobility spectrometer was
      employed for the detection of residual explosives residues on the surfaces of the
      scrap. The mixed microbial populations of the bioslurries effectively
      decontaminated both the scrap and the mortar rounds. Use of the ion mobility
      spectrometer was an extremely sensitive field screening method for assessing
      decontamination and is a method by which minimally trained personnel can declare
      scrap clean with a high level of certainty.

PMID- 14971857
TI  - Transformation of copper oxychloride fungicide into copper oxalate by tolerant
      fungi and the effect of nitrogen source on tolerance.
AB  - Aspergillus niger and Penicillium chrysogenum were able to grow on Czapek Dox
      medium amended with elevated concentrations [up to 500 ppm active ingredient
      (ai)] of the fungicide copper oxychloride. Solubilization of the fungicide in
      solid medium was evident by the appearance of a clear (halo) zone underneath and
      around the growing colonies. The halo formed with A. niger, grown on fungicide
      containing nitrate nitrogen medium, was found subsequently to enclose concentric
      rings of newly crystalline precipitate. These crystals were extracted, examined
      by scanning electron microscopy and IR, and identified as copper oxalate. The
      supplemented nitrogen source to the medium greatly affected both fungicide
      solubilization and fungal tolerance. Ratios of fungicide solubilization rate
      (R(S)) in relation to the colony growth rate (R(G)) were significantly higher on
      ammonium than on nitrate nitrogen medium for both fungal strains. Growth ratios
      (the colony extension rate in the presence of a given concentration of the
      fungicide in relation to the control colony growth rate) of A. niger were
      markedly lower on ammonium than on nitrate nitrogen medium. The cellular copper
      contents, taken up from the fungicide, and the medium titratable acidity were
      higher in ammonium than in nitrate medium for both fungi. These results suggested
      fungal possession of variable tolerance mechanisms to this fungicide by
      complexation and/or precipitation of copper in the medium. Additionally, this
      work emphasizes the activity of fungi in transformation of insoluble inorganic
      metal-containing fungicides into insoluble organic metal compounds, which has a
      potentiality in metal cycling in biogeochemical and environmental context.

PMID- 14971858
TI  - Bioremediation of BTEX hydrocarbons: effect of soil inoculation with the toluene
      growing fungus Cladophialophora sp. strain T1.
AB  - The biodegradation of a mixture of benzene, toluene, ethylbenzene, xylene, (BTEX)
      and methyl-tert-butyl ether (MTBE) was studied in soil microcosms. Soil
      inoculation with the toluene-metabolising fungus Cladophialophora sp. strain T1
      was evaluated in sterile and non-sterile soil. Induction of biodegradation
      capacity following BTEX addition was faster in the soil native microflora than in
      axenic soil cultures of the fungus. Toluene, ethylbenzenes, and the xylenes were
      metabolized by the fungus but biodegradation of benzene required the activity of
      the indigenous soil microorganisms. MTBE was not biodegraded under the tested
      environmental conditions. Biodegradation profiles were also examined under two pH
      conditions after a long term exposure to BTEX. At neutral conditions the presence
      of the fungus had little effect on the intrinsic soil biodegradation capacity. At
      an acidic pH, however, the activity of the indigenous degraders was inhibited and
      the presence of Cladophialophora sp. increased significantly the biodegradation
      rates of toluene and ethylbenzene. Comparison of the BTEX biodegradation rates
      measured in soil batches combining presence and absence of indigenous degraders
      and the fungal inoculum indicated that no severe antagonism occurred between the
      indigenous bacteria and Cladophialophora sp. The presence of the fungal inoculum
      at the end of the experiments was confirmed by PCR-TGGE analysis of small
      subunits of 18S rDNA.

PMID- 14971859
TI  - Functional establishment of introduced chlorobenzoate degraders following
      bioaugmentation with newly activated soil. Enhanced contaminant remediation via
      activated soil bioaugmentation.
AB  - Introduced degraders often do not survive when applied to polluted sites;
      however, the potential for successful bioaugmentation may be increased if newly
      activated soil (containing indigenous degrader populations recently exposed to
      the contaminant) or potentially active soil (containing indigenous degrader
      populations not previously exposed to the contaminant) is used as the inoculant.
      To investigate this concept, Madera and Oversite soils were amended with 0 or 500
      micrograms of 2-, 3-, or 4-chlorobenzoate per gram soil. The Madera degraded 2
      chlorobenzoate while the Oversite degraded 3- and 4-chlorobenzoate. After 22 days
      of incubation, non-active soils that had not degraded chlorobenzoate were
      bioaugmented with the appropriate activated soil that had been exposed to and
      degraded chlorobenzoate. Thus, Oversite soil that had not degraded 2
      chlorobenzoate was bioaugmented with Madera soil that had degraded 2
      chlorobenzoate. Likewise, Madera soil that had not degraded 3- or 4
      chlorobenzoate was bioaugmented with the Oversite soil that had degraded 3- or 4
      chlorobenzoate. Additionally, the non-active soils were bioaugmented with the
      corresponding potentially active soils. The Oversite soil amended with activated
      Madera soil degraded the 2-chlorobenzoate within 3 days of bioaugmentation. The
      Madera soil amended with activated Oversite soils degraded the 3- and 4
      chlorobenzoate within 20 and 6 days, respectively. Large degrader populations
      developed in microcosms bioaugmented with activated soil, and shifts in the 3-
      and 4-CB degrader community structures occurred following bioaugmentation. In
      contrast, bioaugmentation with potentially active soil did not impact
      degradation. The results indicate the potential for bioaugmentation with newly
      activated soil to enhance contaminant degradation.

PMID- 14971860
TI  - Swan song.

PMID- 14971861
TI  - Health care reform: historical and current perspectives.
AB  - Health care in America, criticized today by patients and physicians alike,
      developed incrementally throughout the twentieth century into a system unique to
      the United States. Each effort to change it led to unintended consequences. There
      are many current proposals by presidential candidates and members of Congress for
      reform of the fragmentation of payment for, access to, and quality of care. There
      is increasing pressure from many sources to provide a solution. Will 2004 be the
      year we find it?

PMID- 14971862
TI  - Imipramine vs. sertraline in panic disorder: 24-week treatment completers.
AB  - Despite the acknowledged favorable side effects profile of selective serotonin
      reuptake inhibitors (SSRIs), comparative studies have not found significant
      differences in efficacy between tricyclics (TCAs) such as imipramine and
      clomipramine, and SSRIs in the treatment of panic disorder. The present study
      focuses on treatment completers to inform patients who adhere to a recommended
      course of treatment on the possible differential patterns of improvement and of
      change in side effects between sertraline and imipramine. From an intent to treat
      consecutive sample of patients participating in the 24-week open phase
      protocolized treatment of a long-term controlled maintenance/discontinuation
      study, 20 imipramine completers and 16 sertraline completers with moderate to
      severe baseline symptomatology were compared using primarily repeated measures
      analysis of variance on measures of symptom severity, on 15 side effects
      systematically elicited using an inventory and on heart rate and weight. The
      results revealed greater early improvement with imipramine compared to sertraline
      but no enduring differences beyond week 8 of treatments. Side effects, in
      particular dry mouth, constipation, tremors, sweating, and cardiovascular
      complaints increased more in severity and were more frequent and persistent
      during imipramine than sertraline but, except for the 10 beats/min increase in
      heart rate, side effects were clinically insignificant at the end of both
      treatments. Change in sexual complaints and weight did not differ between the
      treatments. The more favorable side effect profile of SSRIs versus TCAs was
      demonstrated even in the best case scenario of treatment completers. The more
      rapid improvement with imipramine needs replication but, tentatively, it may be
      attributed to the greater motivational effects toward action observed with
      noradrenergic or dual action antidepressants compared to SSRIs.

PMID- 14971863
TI  - Adverse effects and laboratory parameters of high-dose olanzapine vs. clozapine
      in treatment-resistant schizophrenia.
AB  - Patients with treatment-resistant schizophrenia pose a major challenge to
      caregivers since only clozapine is documented as having superior efficacy in this
      population. Although olanzapine is similar to clozapine in structure and receptor
      profile, it has not been proven to have superior efficacy for this patient group.
      Nonetheless, olanzapine is being increasingly used in higher doses as clinicians
      attempt to find a more effective and tolerable therapy for refractory patients.
      Furthermore, there are little data comparing olanzapine and clozapine in this
      population. Thirteen patients participated in a randomized double-blind 16-week
      crossover study of clozapine therapy (450 mg/day) compared to high doses of
      olanzapine (50 mg/day). No patients on olanzapine responded while 20% responded
      to clozapine treatment. Olanzapine patients tended to experience higher rates of
      anticholinergic effects such as dry mouth (80 vs. 20%) and blurry vision (40 vs.
      0%). Clozapine-treated patients had higher rates of sialorrhea (80 vs. 10%),
      sweating (50 vs. 10%), dyspepsia (70 vs. 30%), and lethargy (90 vs. 60%). Neither
      treatment was associated with significant akathisia. Liver enzyme elevation and
      lipids were higher with clozapine treatment. Mean weight gain in the initial 8
      weeks was 3.4 kg for olanzapine and 1.2 kg for clozapine. High doses of
      olanzapine during 8 weeks of treatment did not increase lipids and liver enzymes
      like clozapine did. Olanzapine at 50 mg/day may be associated with more
      anticholinergic effects and weight gain than clozapine.

PMID- 14971864
TI  - Treatment-related adverse events and outcome in a clinical trial of fluoxetine
      for major depressive disorder.
AB  - Treatment-related adverse events (TRAEs), particularly those that occur early on,
      may increase the likelihood for premature discontinuation of antidepressants. The
      purpose of this study was to examine the relationship between TRAEs and outcome
      in depressed outpatients enrolled in an 8-week, 20 mg, open trial of fluoxetine.
      A total of 384 patients (54.7% women, mean age 39.9 +/- 10.5 years) were enrolled
      in the trial. Study visits occurred at baseline and every other week. Somatic
      complaints were assessed during each study visit. Somatic complaints that, in the
      opinion of the evaluating physician, were probably related or related to
      treatment with fluoxetine were entered in the analysis as TRAEs. We then tested
      whether 1) developing at least one TRAE, 2) developing at least one moderate or
      severe TRAE, 3) the number of TRAEs reported during the entire trial, or 4) the
      number of TRAEs reported during each 2-week interval predicted whether patients
      would respond to fluoxetine, or prematurely discontinue treatment. None of the
      above scores predicted whether patients responded to or prematurely discontinued
      the trial. These findings failed to reveal any relationship between side effects
      and treatment outcome for patients with MDD enrolled in an 8-week, 20 mg, fixed
      dose, open trial of fluoxetine.

PMID- 14971865
TI  - Pharmacologic treatment of posttraumatic stress disorder: a focus on
      antipsychotic use.
AB  - To review the literature on the pharmacologic treatment of posttraumatic stress
      disorder (PTSD), with a focus on reports of antipsychotic use for this illness. A
      MEDLINE search (1966-Oct 2002) for English only articles about pharmacologic
      treatment of PTSD. Antipsychotic medications are being used with some frequency
      for PTSD. There are few studies and scant evidence to recommend the traditional
      antipsychotics. There are a number of reports (mostly case reports and open
      trials) in which atypical antipsychotics improved sleep and decreased the
      frequency of nightmares and flashbacks. Some studies showed global improvement
      across symptom clusters. The newer atypical antipsychotics show promise for the
      treatment of PTSD, mainly ameliorating intrusive symptoms. The paucity of double
      blind studies prevents firm conclusions, however, this class of medications may
      be useful particularly for refractory symptoms.

PMID- 14971866
TI  - Matching the bipolar patient and the mood stabilizer.
AB  - Bipolar disorder poses many treatment challenges, including "matching" a
      particular patient with the optimal treatment regimen. Although there are a
      number of extant guidelines to assist the clinician in selecting treatment, these
      recommendations are largely based on general variables and fail to take into
      account the subtleties and complications that confront a clinician in practice.
      An analysis of predictors of medication response in bipolar disorder provides a
      basis for matching patients with optimal medication regimens. Response to
      treatment may depend on the polarity of an episode or on clinical features such
      as mixed or psychotic symptomatology and rate of cycling. Comorbid psychiatric
      disorders such as substance abuse, anxiety disorders, or attention
      deficit/hyperactivity disorder should also be considered in designing a treatment
      regimen. Similarly, medical conditions, especially metabolic abnormalities or
      kidney insufficiency, must be taken into account. Selection of medication may
      also involve an analysis of demographic factors, including family and personal
      history of response to a particular agent. When selecting the most appropriate
      mood stabilizer for a patient--particularly when polypharmacy is required--the
      clinician should keep potential side effects and drug interactions in mind.
      Randomized, controlled studies in bipolar populations are needed to further
      characterize optimal matching of patient and medication.

PMID- 14971867
TI  - Mood stabilizers and treatment adherence in bipolar disorder: addressing adverse
      events.
AB  - Adverse events associated with lithium and anticonvulsant use in patients with
      bipolar disorder have been determined to decrease rates of treatment adherence;
      however, research that explores how adverse events influence treatment adherence,
      and which events have the greatest impact, is sparse and limited. This paper
      reviews the existing literature regarding common side effects encountered with
      lithium and anticonvulsant use in patients with bipolar disorder and presents
      data regarding their impact on treatment adherence. Guidelines for reducing and
      limiting adverse events are highlighted, as are recommendations for improving
      compliance associated with the experience of adverse events in the bipolar
      disorder population.

PMID- 14971868
TI  - What drugs are best for bipolar depression?
AB  - Bipolar depression is a severe, potentially lethal disorder for which there are
      no specific, FDA-indicated pharmacotherapies. Research in this area has been
      limited, and most treatments are based on unsupported extrapolation from the
      treatment of unipolar depression, or follow guidelines derived largely from the
      clinical practice experience of experts in this field. There is clearly a medical
      need for new and more effective treatments for bipolar depression. Recently, the
      newer antiepileptic drugs, and atypical antipsychotics, have been studied to
      evaluate their role in bridging this gap in the psychopharmacologic
      armamentarium. Drugs in these classes will be reviewed, in addition to serotonin
      reuptake inhibitors, monoamine oxidase inhibitors, and electroconvulsive therapy.
      In this paper, current trends in the acute and long-term medication treatment of
      bipolar depression will be described, with particular focus on evidence from the
      existing literature. Additional factors, such as side effects, risk/benefit
      issues, and drug-drug interactions, will be considered in an attempt to make
      overall recommendations for medication selection.

PMID- 14971869
TI  - Atypical antipsychotics in the treatment of delusional parasitosis.
AB  - Delusional parasitosis is the false belief that one's body is infested with one
      or many different living organisms. Historically, it has been treated with
      conventional antipsychotics with only moderate success. The conventional
      antipsychotic most commonly used has been pimozide. We report a series of five
      cases of patients with delusional parasitosis. Our patients' demographic
      characteristics were similar to those in previously published case reports, but
      instead of being treated with older antipsychotics, they were all treated with
      atypical antipsychotic agents with favorable results. We will discuss the
      rationale for this treatment choice, and will review the role of
      serotonin/dopamine antagonists in the treatment of delusional parasitosis. We
      will also comment on the possible role of serotonergic antidepressants in the
      treatment of these patients.

PMID- 14971870
TI  - Prognostic significance of hemostatic parameters in patients with lung cancer.
AB  - There is a subclinical activation of coagulation and fibrinolysis system in lung
      cancer. Alterations in hemostatic system are seen frequently in lung cancer
      correlated with the prognosis of disease. In this prospective study, our purpose
      was to investigate the prognostic significance of hemostatic markers in patients
      with lung cancer. The study comprised 58 patients (22 squamous cell carcinoma, 16
      adenocarcinoma, 20 small cell carcinoma). There were 55 men (95%)and 3 women (5%)
      with a mean age of 61 years range (36-74). Plasma level of platelets (PLT),
      prothrombin time (PT), active partial thromboplastin time (aPTT), antithrombin
      III (AT III), fibrinogen (F) and D-dimer level were measured before the
      initiation of any therapy. Patients were followed up for 17 (12-20) months. The
      median survival was determined as 6.4 months. Three histopathologic groups;
      squamous cell carcinoma, adenocarcinoma and small cell carcinoma were compared
      for the hemostatic parameters. There were no statistically significant
      differences among the histopathologic types for any of the parameters (P > 0.05).
      Patients were divided into two groups as patients without distant metastasis
      (stages I,II,III) and with distant metastasis (stage IV). The group with distant
      metastasis had higher level of D-dimer than the other group (P < 0.05). However,
      there were no statistically significant differences for D-dimer level between
      stages IIIB and IV (P > 0.05). Patients having high D-dimer and low AT III level
      had poor survival in our study. Thus, high level of D-dimer and low AT III level
      were determined as correlated with short survival (P < 0.05). These results
      suggest that elevated plasma level of D-dimer and low AT III level might be a
      sign of poor prognosis in patients with lung cancer.

PMID- 14971871
TI  - COPD exacerbations: the importance of a standard definition.
AB  - Efforts to assess the efficacy of new therapies in the treatment of acute
      exacerbations of chronic obstructive pulmonary disease (COPD) have been hampered
      by the lack of a widely agreed and consistently used definition. A variety of
      definitions have been used in clinical studies, based on changes in patient
      symptoms or the requirement for antibiotic therapy, oral steroids or
      hospitalisation. To date, none of these definitions have been assessed in detail
      for their reliability, responsiveness and validity determined. Considerable
      heterogeneity in the aetiology and manifestation of COPD exacerbations makes
      identification and quantification of defining symptoms extremely difficult. New
      approaches are therefore being sought with a view to identifying a serum or
      tissue marker that can be used as a valuable diagnostic tool. Improvements in
      data recording will also contribute to the accuracy of data retrieval and
      assessment. If we are to progress to a level of sophistication seen in the
      diagnosis and management of other diseases, it is evident that considerable
      research efforts will be required to improve our understanding of COPD
      exacerbations and develop a standard definition for these events, thereby
      facilitating the assessment of therapeutic approaches.

PMID- 14971872
TI  - Smokeless tobacco or nicotine replacement therapy has no effect on serum
      immunoglobulin levels.
AB  - BACKGROUND: Tobacco smokers have lower serum levels of immunoglobulin (Ig)G,
      mainly due to lower levels of IgG2, than non-smokers. The component(s) in tobacco
      smoke responsible for this effect is unknown, but animal studies have implicated
      nicotine as a major contributor to the immunologic effects of smoking. Does
      nicotine exposure due to use of smokeless tobacco (oral moist snuff) or nicotine
      replacement therapy influence serum Ig levels in humans? METHODS: Serum content
      of Ig classes and IgG subclasses was analysed in 77 non-smoking nicotine
      consumers, including 48 users of oral moist snuff (smokeless tobacco users) and
      29 ex-smokers on nicotine replacement therapy, and compared with 44 healthy
      controls. Former smokers in any group had quit smoking at least 6 months prior to
      study entry. Ig class and IgG subclass levels were determined by radial
      immunodiffusion. Systemic nicotine exposure was excluded and confirmed by
      measuring urine content of cotinine using a quantitative radioimmunoassay.
      RESULTS: Ig class and IgG subclass levels did not differ significantly between
      the groups, with the sole exception of IgG4, which was significantly lower in
      nicotine consumers than in healthy subjects (0.4 +/- 0.3 vs. 0.6 +/- 0.4 g/l,
      mean +/- SD, 95% confidence interval [-0.3;-0.05]). There was no correlation
      between any Ig variable and cotinine concentration. CONCLUSIONS: The decreased
      levels of IgG and IgG2 seen in tobacco smokers do not seem to be an effect of
      systemic exposure to nicotine.

PMID- 14971873
TI  - Vascular endothelial growth factor correlates with matrix metalloproteinase-9 in
      the pleural effusion.
AB  - Vascular endothelial growth factor (VEGF) is a potent, multifunctional cytokine
      that contributes to angiogenesis and inflammation. Matrix metalloproteinase-9
      (MMP-9) is one of the major proteolytic enzymes that degrade various components
      of the extracellular matrix. Few data are available on the potential relationship
      between VEGF and MMP-9 in the accumulation of pleural effusion. We examined
      levels of VEGF and MMP-9 by means of enzyme immunoassay, zymographic analysis,
      and Western blot analysis in the patients with liver cirrhosis, tuberculosis, or
      lung cancer. The levels of VEGF and MMP-9 were significantly increased in the
      pleural fluids and sera of patients with tuberculosis and were even higher in
      patients with lung cancer compared with the patients with liver cirrhosis. A
      significant correlation was established between the level of VEGF and the level
      of MMP-9 in the pleural effusion. These results suggest that overproduction of
      VEGF and MMP-9 is associated with accumulation of the pleural effusion in
      tuberculosis and lung cancer. The relationship between VEGF and MMP-9 in the
      pleural effusion may have a role in the pathogenesis of pleural fluid formation.

PMID- 14971874
TI  - Worsening of obstructive sleep apnoeas in a patient with rheumatoid arthritis
      treated with anti-tumor necrosis factor.
AB  - We report on a case of an adult patient treated for rheumatoid arthritis with
      infliximab, a chimerical monoclonal antibody to TNFalpha. Apart from this, the
      patient also showed clinical signs of obstructive sleep apnea syndrome that was
      confirmed by polysomnographic study. After infliximab treatment, additional sleep
      studies revealed an increase in the number of apneic events and SaO2 dips
      suggesting that TNFalpha plays an important role in the pathophysiology of sleep
      apnea. Thus, clinical recognition of sleep disordered breathing should be taken
      into account when rheumatoid arthritis patients are to be treated with
      infliximab.

PMID- 14971875
TI  - Medroxyprogesterone improves cardiac autonomic control in postmenopausal women
      with respiratory insufficiency.
AB  - OBJECTIVE: To study the effect of medroxyprogesterone acetate (MPA) on autonomic
      cardiac control in respiratory insufficiency in postmenopausal women. DESIGN: A
      prospective, single-blind study. SUBJECTS: Eighteen postmenopausal women with
      respiratory insufficiency and eight asymptomatic postmenopausal women with
      nocturnal hypoxaemia as controls. METHODS: Oral MPA treatment was given at 30 mg
      twice daily for 2 weeks. All-night polysomnography including a two-channel
      electroencephalogram, an electro-oculogram, an electromyogram, an
      electrocardiogram, arterial oxyhaemoglobin saturation, maximum end-tidal CO2
      partial pressure, a ballistocardiogram and breathing movements were recorded at
      baseline and at the end of MPA treatment. Heart rate variability (HRV) was
      calculated in time and frequency domains during various sleep stages on and off
      MPA, and the results were correlated to respiratory variables. RESULTS: At
      baseline, patients had higher heart rate and lower HRV than controls, suggesting
      increased cardiac sympathetic output. MPA increased HRV in patients, but not in
      controls. End-tidal CO2 partial pressure decreased, and respiratory rate
      increased during treatment in both groups. CONCLUSIONS: HRV is compromised in
      women with respiratory insufficiency. Peroral MPA increases their HRV to levels
      comparable with those in controls. This suggests an improvement in vagal cardiac
      control beneficial to cardiovascular health.

PMID- 14971876
TI  - Long-term montelukast therapy in moderate to severe COPD--a preliminary
      observation.
AB  - The purpose of this retrospective study was to determine the effects of long-term
      treatment with montelukast on chronic obstructive pulmonary disease (COPD)
      control in a cohort of patients with moderate to severe COPD. The medical records
      of 20 consecutive male patients (18 African-Americans) aged 71.2 +/- 10.7 years
      diagnosed with moderate to severe COPD at the VA Chicago Health Care System,
      Chicago, Illinois, USA, and treated with oral montelukast, 10 mg every night, for
      23.6 +/- 7.3 months were reviewed. Information on demographics and COPD control
      was extracted from each record. In each patient, a comparable follow-up period in
      the clinic before and after initiating montelukast therapy was reviewed and
      tabulated so each patient served as his own control. There was a significant
      improvement in complaints of shortness of breath, sputum production wheezing and
      nocturnal symptoms during the observation period (P < 0.05). There was a
      significant reduction in the use of oral and inhaled corticosteroids, inhaled
      bronchodilators and supplemental oxygen (P < 0.05). In addition, there was a
      significant reduction in the number of visits to the emergency department, number
      of hospitalizations and duration of hospitalizations for acute exacerbations of
      COPD (P < 0.05). No significant changes in FEV1 (% predicted), FEV1/FVC ratio (%
      predicted) and peak expiratory flow rate were recorded during this time. No side
      effects where reported during the observation period and no patient discontinued
      the medication. Collectively, these data suggest that long-term treatment with
      montelukast is safe and improves COPD control in elderly patients with moderate
      to severe COPD.

PMID- 14971877
TI  - Mechanisms of chronic airway obstruction in smokers.
AB  - Studies over the past few decades have showed a clear association between
      cigarette smoking and the development of chronic airway obstruction. Yet, only a
      minority of smokers is affected so that in many, even heavy, smokers, pulmonary
      function remains within normal limits. While carcinogens have been well
      characterized, there is only limited information about the constituents of
      cigarette smoke responsible for inducing chronic airway obstruction. In addition,
      the associated risks factors for airway obstruction in smokers have not been
      totally identified. The present paper is a review of the recently accumulated
      facts concerning the intimate action of cigarette smoke at the level of large and
      small airways and lung parenchyma. The role of classical inflammatory cells such
      as neutrophils and alveolar macrophages is reviewed, but emphasis is put on
      recent evidence indicating the involvement of CD8 + T-lymphocytes and possibly
      eosinophils in the genesis of the structural changes leading to airways
      obstruction. The mechanisms by which airway inflammation and remodelling cause
      airway narrowing and airflow limitation are discussed, along with the associated
      loss of lung elasticity secondary to destructive emphysema. Other biological,
      epidemiological, physiopathological, and clinical aspects are analyzed, stressing
      such fundamental aspects as the defence mechanisms, the morpho-functional
      correlations, the identification of susceptible smokers, and the early detection
      of airway obstruction, both in specialized laboratories and in primary care.

PMID- 14971878
TI  - Relative accuracy of algorithm-based prescription of nasal CPAP in OSA.
AB  - BACKGROUND: Patients with OSA on nasal continuous positive airway pressure (CPAP)
      have considerable night-to-night variation in their pressure requirements,
      suggesting that a one-night titration might not be very precise. This study
      investigates the likely error incurred using a one-night titration, and explores
      whether an algorithm-based approach to determine the pressure is as accurate.
      METHODS: Thirty patients with OSA used an autotitrating CPAP device for 28 nights
      and the average was regarded as the 'reference' pressure for that patient. Using
      estimates of precision and bias, this 'reference' pressure was compared with (1)
      an algorithm-derived pressure (based on neck circumference and OSA severity), (2)
      a one-night titration (using four alternative nights), and (3) a fixed pressure
      of 10 cmH2O. RESULTS: The mean 'reference' pressure for the group was 9.83 (SD
      2.12) cmH2O. There was little bias from any of the alternatives. However, the
      precision varied between 1.65 and 2.45 cmH2O for the four one-night titrations,
      was 2.00 for the algorithm, and was 2.12 using a fixed pressure of 10 cmH2O.
      CONCLUSIONS: Considerable night-to-night variation means that a one-night
      titration is not very precise and is subject to random variation. A one-night
      titration has a similar inaccuracy to that resulting from using an algorithm,
      based on OSA severity and neck circumference. Setting all patients with OSA at 10
      cmH2O is little worse.

PMID- 14971879
TI  - A novel, simplified approach to starting nasal CPAP therapy in OSA.
AB  - BACKGROUND: Due to ever increasing referral rates, we have had to move the nasal
      CPAP induction program for patients with obstructive sleep apnoea (OSA) out of
      the sleep laboratories and into an outpatient setting. We report the effects this
      has had on patient outcomes. METHODS: The last 75 patients with OSA who had an
      overnight CPAP titration in the sleep laboratory (group 1) were compared with the
      first 75 coming to an afternoon clinic and set up on CPAP in groups, and who had
      their CPAP pressure determined from an algorithm (group 2). They were assessed at
      1 and 11 months using the Epworth Sleepiness Score, compliance with CPAP
      (h/night), whether still using CPAP, and the number of clinic appointments
      required in the first 11 months. RESULTS: The two groups were similar at
      baseline. There were no differences in any of the outcome measures. ESS values
      fell from 14.6 to 5.0 and from 14.0 to 5.1 at 11 months in groups 1 and 2,
      respectively: compliance, 5.2 versus 5.1 h/night; clinic appointments, 1.75
      versus 1.96; discontinuation rates at 1 month, 8% and 7%, and at 11 months, 25%
      and 21%. CONCLUSIONS: Using these simple outcome measures, we have shown that
      using an outpatient-based approach, and CPAP pressure based on an algorithm, have
      not reduced the efficacy of our CPAP induction program for patients with OSA.

PMID- 14971880
TI  - BAL levels of interleukin-18 do not change before or during acute rejection in
      lungtransplant recipients.
AB  - STUDY OBJECTIVE: Acute rejection (AR) of the allograft is a major clinical
      problem after lungtransplantation. Repeated episodes of AR increase the risk of
      developing obliterative bronchiolitis, the main cause of mortality in this
      patient group. It is believed that AR is caused by T-lymphocytes reacting to
      donor antigens and in turn activating antigen presenting cells (APC) such as
      alveolar macrophages. Hypothetically, the interferon-gamma inducing cytokine IL
      18 released from activated macrophages can play a role in the development of AR
      by modulating cytotoxic T-lymphocytes. DESIGN: To determine whether IL-18 may
      serve as a marker of AR, we retrospectively analysed the concentration of soluble
      IL-18 protein and inflammatory cells in bronchoalveolar lavage fluid (BAL) from
      lungtransplant recipients. PATIENTS: To minimize confounding factors, eight pairs
      of patients were matched for age, gender, pre-op diagnosis, type of operation,
      absence of infection and time post transplant. METHODS: BAL levels of IL-18
      (ELISA) and BAL cell differentials were analysed before, during and after an
      episode of AR and compared with the matched control group. CONCLUSION: We found
      no changes in IL-18 concentration in BAL associated with AR. IL-18 in BAL did not
      correlate with BAL lymphocyte percentage. We conclude that change in soluble IL
      18 protein does not constitute a useful marker of acute rejection in lung
      allograft recipients.

PMID- 14971881
TI  - Overexpression of cyclooxygenase-2 in non-small cell lung cancer.
AB  - Evidence is accumulating to suggest that the inducible isoenzyme of
      cyclooxygenase (COX)-2 is up-regulated in human cancers and epidemiological
      studies indicate that COX inhibitors may have a protective effect on the
      development of lung cancer. We used immunohistochemistry and Western blotting to
      investigate COX expression in lung tumour specimens and three lung cancer cell
      lines. Sixty-five archival lung tissue samples, including 46 squamous cell and 6
      adenocarcinoma lung resections, and 13 small cell lung cancer (SCLC) biopsies
      were studied. Dense and intense cytoplasmic COX-2 staining was found in all 52
      resections from non-small cell lung cancer (NSCLC). The staining was diffuse and
      much stronger than adjacent respiratory epithelium. COX-2 staining was relatively
      weak in the majority of the SCLC samples. The bronchial and bronchiolar
      epithelium in the surrounding normal lung structures showed uniform COX
      immunoreactivity with apical concentration of the stain. There was no increase in
      COX-1 staining in any tumour type. Western blot analysis of the cancer lines
      revealed significantly higher expression of COX-1 in CORL23 line and COX-2 in two
      NSCLC cell lines (MOR/P; A549) compared with the expression of COX-1 and COX-2 in
      cultured normal bronchial epithelial cells. Our findings demonstrated COX-2
      overexpression in NSCLC.

PMID- 14971882
TI  - Determination of the serum matrix metalloproteinase-9 (MMP-9) and tissue
      inhibitor of matrix metalloproteinase-1 (TIMP-1) in patients with either advanced
      small-cell lung cancer or non-small-cell lung cancer prior to treatment.
AB  - This study was undertaken to examine the relationship between circulating matrix
      metalloproteinase (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP
      1) in our patients with either advanced small-cell lung cancer (SCLC) or non
      small-cell lung cancer (NSCLC) prior to treatment. Thirty-one male and female
      patients with either stage III or IV NSCLC and 17 with either stage III or IV
      SCLC were compared to 117 age matched non-smoking controls of both sexes. Prior
      to any treatment of the patient, a baseline serum sample was obtained from each
      of the patients for the determination of circulating MMP-9 and TIMP-1 by ELISA.
      The results indicate that both MMP-9 and TIMP-1 are elevated in the serum of lung
      cancer patients when compared to the controls. This observation was true for both
      SCLC and NSCLC. However, the mean values for both MMP-9 and TIMP-1 in the two
      tumors were not different from each other. The natural physiological relationship
      between MMP-9 and the inhibitor TIMP-1 was lost in both SCLC and NSCLC,
      indicative of abnormal alterations by the tumor. The data from this study
      suggests that advanced lung cancer does alter the normal circulatory pattern of
      MMP-9 and TIMP-1. This could aid in the processes of tumor invasion and/or
      metastasis.

PMID- 14971883
TI  - Is there any correlation between the ATS, BTS, ERS and GOLD COPD's severity
      scales and the frequency of hospital admissions?
AB  - Disagreement exists between different COPD guidelines considering classification
      of severity of the disease. The aim of our study was to determine whether there
      is any correlation between severity scales of various COPD guidelines (ATS, BTS,
      ERS and GOLD) and the frequency of hospitalisations for COPD exacerbation. A
      cohort of 67 COPD patients (65 male 2 female, 45 ex-smokers, 22 current smokers,
      aged (69.4 +/- 1.1)) was recruited from those admitted in the pulmonary clinic of
      the University Hospital of Heraklion, Crete for an acute exacerbation. Lung
      function tests and arterial blood gases analyses were performed during stable
      conditions at a scheduled visit 2 months after discharge. The patients were
      stratified using the FEV1 percent-predicted measurement of this visit into mild,
      moderate and severe in accordance to the ATS, BTS, ERS and GOLD scales of
      severity. The number of hospitalisations for acute exacerbation was recorded for
      the following 18 months. A total of 165 exacerbations were recorded. The
      correlation between the severity of COPD and the number of hospitalisations per
      year was statistically significant using the GOLD classification system of
      severity (P = 0.02 and r = 0.294). A weak correlation was also found between the
      number of hospitalisations and the ERS classification system (P = 0.05 and r =
      0.24). No statistically significant correlation was found between the number of
      hospitalisations and the ATS or BTS severity scales. In conclusion the GOLD and
      ERS classification systems of severity of COPD correlated to exacerbations
      causing hospitalisation. The same was not true for the ATS and BTS severity
      scales. Better correlation was achieved with the GOLD scale.

PMID- 14971884
TI  - Clinical assessment of asthma severity partially corresponds to sputum
      eosinophilic airway inflammation.
AB  - In the aim to evaluate the relationship between sputum eosinophil percentages and
      eosinophil cationic protein (ECP) concentrations, as markers of airway
      inflammation, and different Levels of asthma severity, we examined 223 patients
      consecutively observed in our asthma clinic. Diagnosis of asthma was made
      according to internationally accepted criteria. Asthma severity was evaluated
      according to frequency of symptoms, FEV1, peak expiratory flow variability and
      level of asthma treatment needed to control asthma. Spontaneous or induced sputum
      was collected. Adequate sputum samples were obtained in 68 untreated subjects and
      in 117 subjects regularly treated with ICS. A control group of 14 normal subjects
      was also examined. In untreated subjects, mild intermittent asthmatics showed a
      lower sputum eosinophil percentage in comparison with other groups of asthma
      severity, while no difference in ECP levels was detected. In treated subjects,
      severe asthmatics showed higher levels of sputum eosinophils and ECP in
      comparison with other groups of asthma severity. Mild persistent and moderate
      persistent patients did not differ for sputum eosinophils or ECP in both
      untreated and treated subjects. Controls were significantly different from all
      groups of untreated and treated asthmatics. In conclusion, the assessment of
      asthma severity according to clinical and functional findings only partially
      corresponds to the severity of eosinophilic airway inflammation as assessed by
      induced sputum analysis.

PMID- 14971885
TI  - Long-term progestin therapy for female chronic respiratory insufficiency?
AB  - End-stage chronic obstructive pulmonary disease often leads to hypercapnic
      respiratory failure. Oxygen supplementation therapy may further aggravate
      hypercapnia and not all patients are compliant with non-invasive ventilation.
      This case documents successful control of chronic respiratory failure with
      medroxyprogesterone in a postmenopausal woman during 1-year follow-up.

PMID- 14971886
TI  - New class of corticotropin-releasing factor (CRF) antagonists: small peptides
      having high binding affinity for CRF receptor.
AB  - The discovery of small and potent peptide antagonists of the corticotropin
      releasing factor (CRF) receptor is described. Through the structure-activity
      relationship studies of 12-amino acid peptide corresponding to the C-terminal
      residues of astressin, we assumed that a particular surface of the alpha-helix
      was important for binding to the receptor. The small peptide containing d-Ala31
      and cyclohexylalanine38 on that surface was as potent as astressin in binding to
      the CRF receptor and showed significant ACTH suppression when administered to
      rats.

PMID- 14971887
TI  - Sabadinine: a potential non-peptide anti-severe acute-respiratory-syndrome agent
      identified using structure-aided design.
AB  - A novel human coronavirus has been reported to be the causative agent of severe
      acute respiratory syndrome (SARS). Since replication of HcoVs depends on
      extensive proteolytic processing, the main proteinase, 3CLpro, is an attractive
      drug target for anti-SARS agents. We have employed molecular docking of a
      chemical database into the active site of 3CLpro to search for non-peptidyl
      inhibitors. One compound was identified to be the natural product sabadinine,
      isolated from a historical herbal remedy.

PMID- 14971888
TI  - Small molecule mitochondrial F1F0 ATPase hydrolase inhibitors as cardioprotective
      agents. Identification of 4-(N-arylimidazole)-substituted benzopyran derivatives
      as selective hydrolase inhibitors.
AB  - In this paper we show that 4-aryl-CH2-imidazole-substituted benzopyran compounds
      with 3S,4R-stereochemistry are cardioprotective by inhibiting the F1F0
      mitochondrial ATP hydrolase. Compounds (e.g., 13) with 3R,4S-stereochemistry act
      as mitochondrial KATP openers. This resulted from an inversion of stereochemistry
      for the F1F0 mitochondrial ATP hydrolase vs mitochondrial KATP. Structure
      activity relationships for the inhibition of mitochondrial ATP hydrolase are also
      delineated. It is not clear how 13 (3R,4S) can selectively inhibit the hydrolytic
      activity of the F1F0 mitochondrial enzyme without interfering with the synthase
      activity.

PMID- 14971889
TI  - Nonpeptide luteinizing hormone-releasing hormone antagonists derived from
      erythromycin A: design, synthesis, and biological activity of cladinose
      replacement analogues.
AB  - The design and synthesis of a series of 11,12-cyclic carbamate derivatives of 6-O
      methylerythromycin A that are novel, nonpeptide LHRH antagonists, is described.
      The macrolide antagonist 1, discovered during a screen of our chemical
      repository, was compared to a macrocyclic peptide antagonist 2 using molecular
      modeling, thus providing a model for the design of more potent antagonists.
      Medicinal chemistry efforts to find a replacement for cladinose at position 3 of
      the erythronolide core provided a series of oxazolidinone carbamates that were
      equally as active as the cladinose-containing parent macrolides. The descladinose
      LHRH antagonist 14 has 1-2 nM affinity for both rat and human LHRH receptors and
      is a potent inhibitor of LH release (pA2 = 8.76) in vitro. In vivo, 14 was found
      to produce a dose-dependent suppression of LH in male castrate rats via both i.v.
      and p.o. dosing.

PMID- 14971890
TI  - 3-(4-Aroyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-propenamides as a new class of
      synthetic histone deacetylase inhibitors. 2. Effect of pyrrole-C2 and/or -C4
      substitutions on biological activity.
AB  - Previous SAR studies (Part 1: Mai, A.; et al. J. Med. Chem. 2003, 46, 512-524)
      performed on some portions (pyrrole-C4, pyrrole-N1, and hydroxamate group) of 3
      (4-benzoyl-1-methyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamide (1a) highlighted its
      4-phenylacetyl (1b) and 4-cynnamoyl (1c) analogues as more potent compounds in
      inhibiting maize HD2 activity in vitro. In the present paper, we investigated the
      effect on anti-HD2 activity of chemical substitutions performed on the pyrrole-C2
      ethene chains of 1a-c, which were replaced with methylene, ethylene, substituted
      ethene, and 1,3-butadiene chains (compounds 2). Biological results clearly
      indicated the unsubstituted ethene chain as the best structural motif to get the
      highest HDAC inhibitory activity, the sole exception to this rule being the
      introduction of the 1,3-butadienyl moiety into the 1a chemical structure
      (IC50(2f) = 0.77 microM; IC50(1a) = 3.8 microM). IC50 values of compounds 3,
      prepared as 1b homologues, revealed that between benzene and carbonyl groups at
      the pyrrole-C(4) position a hydrocarbon spacer length ranging from two to five
      methylenes is well accepted by the APHA template, being that 3a (two methylenes)
      and 3d (five methylenes) are more potent (2.3- and 1.4-fold, respectively) than
      1b, while the introduction of a higher number of methylene units (see 3e,f)
      decreased the inhibitory activities of the derivatives. Particularly, 3a (IC50 =
      0.043 microM) showed the same potency as SAHA in inhibiting HD2 in vitro, and it
      was 3000- and 2.6-fold more potent than sodium valproate and HC-toxin and was 4.3
      and 6-fold less potent than trapoxin and TSA, respectively. Finally,
      conformationally constrained forms of 1b,c (compounds 4), prepared with the aim
      to obtain some information potentially useful for a future 3D-QSAR study, showed
      the same (4a,b) or higher (4c,d) HD2 inhibiting activities in comparison with
      those of the reference drugs. Molecular modeling and docking calculations on the
      designed compounds performed in parallel with the chemistry work fully supported
      the synthetic effort and gave insights into the binding mode of the more flexible
      APHA derivatives (i.e., 3a). Despite the difference of potency between 1b and 3a
      in the enzyme assay, the two APHA derivatives showed similar antiproliferative
      and cytodifferentiating activities in vivo on Friends MEL cells, being that 3a is
      more potent than 1b in the differentiation assay only at the highest tested dose
      (48 microM).

PMID- 14971891
TI  - Synthesis and chemical-pharmacological characterization of the antimetastatic
      NAMI-A-type Ru(III) complexes (Hdmtp)[trans-RuCl4(dmso-S)(dmtp)], (Na)[trans
      RuCl4(dmso-S)(dmtp)], and [mer-RuCl3(H2O)(dmso-S)(dmtp)] (dmtp = 5,7
      dimethyl[1,2,4]triazolo[1,5-a]pyrimidine).
AB  - Ruthenium compounds have gained large interest for their potential application as
      chemotherapeutic agents, and in particular the complexes of the type (X)[trans
      RuCl4(dmso-S)L] (X = HL or Na, NAMI-A or NAMI, respectively, for L = imidazole)
      are under investigation for their antimetastatic properties. The NAMI(-A)-like
      compounds are prodrugs that hydrolyze in vivo, and the investigation of their
      hydrolytic properties is therefore important for determining the nature of the
      potential active species. The NAMI-A-type Ru(III) complex 1, (Hdmtp)[trans
      RuCl4(dmso-S)(dmtp)] (dmtp is 5,7-dimethyl[1,2,4]triazolo[1,5-a]pyrimidine), and
      the corresponding sodium analogue 2, (Na)[trans-RuCl4(dmso-S)(dmtp)], were
      synthesized. The hydrolyses of 1 and 2 in water as well as in buffered solutions
      were studied, and the first hydrolysis product, [mer-RuCl3(H2O)(dmso
      S)(dmtp)].H2O (3), was isolated and characterized. The molecular structures of 1
      and 3 were determined by single-crystal X-ray diffraction analyses and prove the
      importance of the hydrogen-bonding properties of dmtp to stabilize hydrolysis
      products. In vitro 1 (a) is not cytotoxic on tumor cells, following challenges
      from 1 to 72 h and concentrations up to 100 microM, (b) inhibits matrigel
      invasion at 0.1 mM and MMP-9 activity with an IC50 of about 1 mM, and (c) is
      devoid of pronounced effects on cell distribution among cell cycle phases. In
      vivo compound 1, similar to NAMI-A, significantly inhibits metastasis growth in
      mice bearing advanced MCa mammary carcinoma tumors. In the lungs, 1 is
      significantly less concentrated than NAMI-A, whereas no differences between these
      two compounds were found in other organs such as tumor, liver, and kidney.
      However, 1 caused edema and necrotic areas on liver parenchyma that are more
      pronounced than those caused by NAMI-A. Conversely, glomerular and tubular
      changes on kidney are less extensive than with NAMI-A. In conclusion, 1 confirms
      the excellent antimetastatic properties of this class of NAMI-A-type compounds
      and qualifies as an interesting alternative to NAMI-A for treating human cancers.

PMID- 14971892
TI  - Synthesis, radiosynthesis, and biological evaluation of carbon-11 and iodine-123
      labeled 2beta-carbomethoxy-3beta-[4'-((Z)-2-haloethenyl)phenyl]tropanes:
      candidate radioligands for in vivo imaging of the serotonin transporter.
AB  - 2beta-Carbomethoxy-3beta-[4'-((Z)-2-iodoethenyl)phenyl]tropane (ZIET) and 2beta
      carbomethoxy-3beta-[4'-((Z)-2-bromoethenyl)phenyl]tropane (ZBrET) were
      synthesized as well as their nortropane congeners ZIENT and ZBrENT. Binding
      affinities of these compounds were determined in cells transfected to express
      human SERT, DAT, and NET using [3H]citalopram, [125I]RTI-55, and [3H]nisoxetine,
      respectively. Both ZIET and ZBrET displayed high affinity for the SERT (Ki = 0.11
      and 0.08 nM, respectively). The affinities of ZIET and ZBrET for the DAT were 200
      and 38-fold lower, respectively, than for the SERT. [11C]ZIET and [11C]ZBrET were
      prepared by alkylation of their corresponding nortropanes with [11C]methyl iodide
      in approximately 30% radiochemical yield (decay-corrected to end of bombardment,
      EOB). High specific activity [123I]ZIET was synthesized in 33% radiochemical
      yield (decay-corrected) by treating the 2beta-carbomethoxy-3beta-[4'-((Z)-2
      trimethylstannylethenyl)phenyl]tropane (3) with no carrier-added sodium
      [123I]iodide and hydrogen peroxide in ethanolic HCl. Biodistribution studies in
      rats indicated that [123I]ZIET enters the brain readily and accumulates in SERT
      rich regions. Blocking studies performed in rats demonstrated that [123I]ZIET was
      selective and specific for SERT-rich regions (e.g. thalamus, brainstem, and
      striatum). MicroPET brain imaging studies in monkeys demonstrated that [11C]ZIET
      and [11C]ZBrET uptakes were selectivity localized in the putamen, midbrain,
      caudate, thalamus, pons, and medulla. Radioactivity in the regions of high SERT
      density of monkey brain was displaceable with citalopram except in the putamen
      and caudate. Radioactivity uptake in these DAT-rich regions was significantly
      displaceable either by preadministration of citalopram followed by injection of
      RTI-113 (or vice-versa) or by administration of a mixture of DAT and SERT
      ligands. In conclusion, the high yield, high specific activity, one-step
      radiolabeling method, high selectivity and favorable kinetics, and the good
      results obtained with [123I]ZIET in rats support the candidacy of [11C]ZIET for
      in vivo visualization and quantification of brain SERT.

PMID- 14971893
TI  - Benzo[f]azino[2,1-a]phthalazinium cations: novel DNA intercalating chromophores
      with antiproliferative activity.
AB  - New azaquinolizinium-type cations have been obtained from isochromane. The
      synthesis was completed over seven steps and included as the key feature an
      intramolecular Westphal condensation. This first example of the intramolecular
      process allowed the preparation of benzo[f]pyrido[2,1-a]phthalazinium and
      benzo[f]quino[2,1-a]phthalazinium salts, which were evaluated as DNA
      intercalators, DNA topoisomerase I inhibitors, and antiproliferative compounds.
      Both cationic systems behave as DNA intercalators and exhibit antiproliferative
      activity. The pentacyclic benzo[f]quino[2,1-a]phthalazinium cations also have an
      inhibitory effect on the catalytic activity of DNA topoisomerase I, without
      trapping of cleavage complexes. Structural characterization using density
      functional theory indicates that the fused ring systems are slightly nonplanar,
      and additional molecular modeling studies suggest a preferred orientation for the
      intercalating chromophores within a typical CpG or TpG intercalation site.

PMID- 14971894
TI  - Antineoplastic agents. 520. Isolation and structure of irciniastatins A and B
      from the Indo-Pacific marine sponge Ircinia ramosa.
AB  - The Indo-Pacific marine sponge Ircinia ramosa has been found to contain two
      powerful (GI50 from 0.001 to <0.0001 microg/mL) murine and human cancer cell
      growth inhibitors. Both were isolated (10(-3)-10(-4)% yields) by cancer cell line
      bioassay-guided techniques and named irciniastatins A (1) and B (2). Structural
      elucidation by a combination of spectral analyses, primarily high resolution mass
      and 2D-NMR (principally APT, HMQC, HMBC, and ROESY) spectroscopy, revealed the
      unusual structures 1 and 2.

PMID- 14971895
TI  - Structure-activity studies of orexin a and orexin B at the human orexin 1 and
      orexin 2 receptors led to orexin 2 receptor selective and orexin 1 receptor
      preferring ligands.
AB  - The neuropeptides orexin A and B (also known as hypocretins) play an important
      role in many physiological and behavioral activities. Orexins are ligands of two
      closely related G-protein-coupled receptors, that are the named orexin 1 and
      orexin 2 receptors. To clearly identify the minimal ligand sequences required for
      receptor activation, we synthesized and analyzed different centrally, C- and N
      terminally truncated analogues of orexins A and B. Furthermore, we used the
      shortest active analogue to screen for important amino acid residues by l-alanine
      and l-proline replacement scans. For orexin A, only full-length peptides were
      able to show the same activity as orexin A, but interestingly, reduced orexin A
      and natural orexin A, which contains the two disulfide bonds, had the same
      activity. The shortest highly active orexin B analogue was orexin B 6-28. In
      addition, we identified orexin A 2-33 as the first analogue with orexin 1
      receptor preference and orexin B 10-28, [A27]orexin B 6-28, and [P11]orexin B 6
      28 as being highly potent orexin 2 receptor selective (>1000-fold) peptides.

PMID- 14971896
TI  - Linker length modulates DNA cross-linking reactivity and cytotoxic potency of
      C8/C8' ether-linked C2-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD)
      dimers.
AB  - A C2/C2'-exo-unsaturated pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer 4b (DRG
      16) with a C8-O(CH2)nO-C8' diether linkage (n = 5) has been synthesized that
      shows markedly superior in vitro cytotoxic potency (e.g., >3400-fold in IGROV1
      ovarian cells) and interstrand DNA cross-linking reactivity (>10-fold) compared
      to the shorter homologue 4a (SJG-136; n = 3). In contrast, for the C-ring
      unsubstituted series, the corresponding n = 5 dimer (3c) is generally less
      cytotoxic and has a lower interstrand cross-linking reactivity compared to its
      shorter n = 3 homologue (3a). Dimer 4b cross-links DNA with >10-fold efficiency
      compared to 4a, and also inhibits the activity of the restriction endonuclease
      BamH1 more efficiently than either 3a or 4a. The C2-exo-unsaturated PBD dimers
      4a,b are not only more effective than their C-ring saturated counterparts in
      terms of induced DeltaTm shift, but they also exert this effect more rapidly.
      Thus, while 3a and 3c exert 68 and 35% of their maximum effect immediately upon
      interaction with DNA, this level increases to 76 and 97% for 4a and 4b,
      respectively. Molecular modeling shows a rank order of 4b (n = 5) > 4a (n = 3) >
      3a (n = 3) > 3c (n = 5) in terms of binding energy toward duplexes containing
      embedded target 5'-GAT(1-2)C cross-link sequences, reflecting the superior fit of
      the C2-exo-unsaturated rather than saturated C-rings of the PBD dimers. A novel
      synthesis of core synthetic building blocks for PBD dimers via stepwise Mitsunobu
      reaction and nitration with Cu(NO3)2 is also reported.

PMID- 14971897
TI  - Novel benzophenones as non-nucleoside reverse transcriptase inhibitors of HIV-1.
AB  - GW4511, GW4751, and GW3011 showed IC50 values < or =2 nM against wild type HIV-1
      and <10 nM against 16 mutants. They were particularly potent against NNRTI
      resistant viruses containing Y181C-, K103N-, and K103N-based double mutations,
      which account for a significant proportion of the clinical failure of the three
      currently marketed NNRTIs. The antiviral data together with the favorable
      pharmacokinetic data of GW4511 suggested that these benzophenones possess
      attributes of a new NNRTI drug candidate.

PMID- 14971898
TI  - Potent nonclassical nucleoside antiviral drugs based on the N,N-diarylformamidine
      concept.
AB  - New formamidine-3TC (3TC = 2',3'-dideoxy-3'-thiacytidine) analogues have been
      synthesized through various methods, and their antiviral activities (HIV, HBV)
      have been evaluated in vitro. Anti-HIV-1 in acutely infected MT-4 cells and
      peripheral blood monocellular cells (PBMCs) showed that compounds substituted by
      N,N-diarylformamidine side chains at the 4-N nucleic base position (compounds 3
      and 8-11) had at least equivalent anti-HIV activity as 3TC (EC50 = 0.5 and 11.6
      microM, respectively). Moreover, the newly synthesized compounds demonstrated
      higher anti-HBV activity (EC50 ranging from 0.01 to 0.05 microM) compared to the
      parent nucleoside 3TC (EC50 = 0.2 microM). It should be underlined that these new
      promising derivatives inhibited HIV in cells of a macrophage lineage, which are
      known to be cellular reservoir for HIV. These results were particularly of
      interest, since the antiviral activities appeared not to be mediated through the
      formamidine bond hydrolysis and consequently the release of free 3TC. These new
      analogue series were found to be highly stable to hydrolysis even after prolonged
      incubation in different biological media (t(1/2) ranged from 48 to 120 h). This
      enzymatic stability, coupled to the fact that no delay in the antiviral response
      was observed compared to the free 3TC antiviral response, suggest that this new
      N,N-diarylformamidine nucleoside series should not be considered as classical
      prodrugs.

PMID- 14971899
TI  - Design, synthesis, and biological evaluation of doxorubicin-formaldehyde
      conjugates targeted to breast cancer cells.
AB  - The anthracycline antitumor drug doxorubicin (DOX) has been utilized for decades
      as a broad-spectrum chemotherapeutic. Recent literature evidence documents the
      role of formaldehyde in the cytotoxic mechanism, and anthracycline-formaldehyde
      conjugates possess substantially enhanced activity in vitro and in vivo.
      Targeting a doxorubicin-formaldehyde conjugate specifically to cancer cells may
      provide a more efficacious chemotherapeutic. The design and 11-step synthesis of
      doxorubicin-formaldehyde conjugates targeted to the estrogen receptor, which is
      commonly overexpressed in breast cancer cells, are reported. The formaldehyde is
      incorporated in a masked form as an N-Mannich linkage between doxorubicin and
      salicylamide. The salicylamide triggering molecule, previously developed to
      release the doxorubicin-formaldehyde active metabolite, is tethered via
      derivatized ethylene glycols to an E and Z mixture of 4-hydroxytamoxifen. The
      targeting group, E/Z-4-hydroxytamoxifen, was selected for its ability to tightly
      bind the estrogen receptor and antiestrogen binding sites. The targeted
      doxorubicin-formaldehyde conjugates' estrogen receptor binding and in vitro
      growth inhibition were evaluated as a function of tether length. The lead
      compound, DOX-TEG-TAM, bearing a triethylene glycol tether, binds the estrogen
      receptor with a binding affinity of 2.5% relative to E/Z-4-hydroxytamoxifen and
      inhibits the growth of four breast cancer cell lines with 4-fold up to 140-fold
      enhanced activity relative to doxorubicin.

PMID- 14971900
TI  - Synthesis of 2',5'-dideoxy-2-fluoroadenosine and 2',5'-dideoxy-2,5'
      difluoroadenosine: potent P-site inhibitors of adenylyl cyclase.
AB  - Glycosylation of 2-fluoroadenine with the appropriate protected thioglycoside
      derivatives, followed by deprotection and anomer separation, produced the alpha-
      and beta-anomers of 2',5'-dideoxy-2-fluoroadenosine (1), 2',5'-dideoxy-2,5'
      difluoroadenosine (2), and 2'-deoxy-2-fluoroadenosine (3). These were examined as
      P-site inhibitors of adenylyl cyclase. The presence of fluorine on the purine
      ring increased potency of inhibition, and the most potent compound, beta-2',5'
      dideoxy-2-fluoroadenosine (1b), was 3 times more potent than beta-2',5'
      dideoxyadenosine.

PMID- 14971901
TI  - Synthesis and biological evaluation of new selective cytotoxic cyclolignans
      derived from podophyllotoxin.
AB  - Podophyllotoxin and some of its derivatives are cyclolignans currently used for
      removing warts and in the clinical treatment of malign neoplasms. As such, they
      have been an objective of the scientific community for decades, in the search for
      more potent and more selective anticancer agents. Our interest in the
      chemoinduction of drug selectivity led us to the design and preparation of new
      podophyllotoxin derivatives by reaction of podophyllic aldehyde with aliphatic,
      aromatic, and heteroaromatic amines. Several of the resulting imines displayed a
      significant selectivity against human colon carcinoma cells, even higher than
      that of the starting aldehyde. Additional biological studies indicate that these
      derivatives induce microtubule depolymerization, arrest cells at the G2/M phase
      of cell cycle, and are able to induce a delayed apoptosis after 48 h of
      treatment, characterized by caspase-3 activation.

PMID- 14971902
TI  - Structure-activity relationships of small phosphopeptides, inhibitors of Grb2 SH2
      domain, and their prodrugs.
AB  - To develop potential antitumor agents directed toward HER2/ErbB2 overexpression
      in cancer, we have designed inhibitors of the recognition between the
      phosphotyrosine of the receptor and the SH2 domain of the adaptor protein Grb2.
      In the first part of the paper, we report the synthesis of mimetics of the
      constrained (alpha-Me)phosphotyrosine residue such as (alpha-Me)-4
      phosphonomethylphenylalanine (-CH2PO3H2), (alpha-Me) 4
      phosphonodifluoromethylphenylalanine (-CF2PO3H2), and (alpha-Me)-4
      phosphonophenylalanine (-PO3H2). The incorporation of these residues in the mAZ
      pTyr-Xaa-Asn-NH2 series provided compounds with very high affinity for the Grb2
      SH2 domain, in the 10(-8)-10(-9) range of Kd values. These compounds behave as
      potent antagonists of the Grb2-Shc interaction. Our results highlight the
      importance of the doubly negative charge borne by the pY + 1 amino acid in
      accordance with the interactions observed in the complex crystallized between mAZ
      pTyr-(alphaMe)pTyr-Asn-NH2 and the Grb2 SH2 domain. mAZ-pTyr-(alphaMe)pTyr-Asn
      NH2 was derivatized as the S-acetyl thioester (SATE) of the phosphotyrosine
      residues, and its surrogates provided prodrugs with very potent antiproliferative
      activity on cells overexpressing HER2/ErbB2, with ED50 values amounting to 0.1
      microM. Finally a new prodrug is put forth under the form of a monobenzyl ester
      of phosphate group that is as active as and much easier to synthesize than SATE
      prodrugs. These compounds show promising activity for further testing on in vivo
      models.

PMID- 14971903
TI  - Chemical and functional identification and characterization of novel sulfated
      alpha-conotoxins from the cone snail Conus anemone.
AB  - An LC/MS analysis with diagnostic screening for the detection of peptides with
      posttranslational modifications revealed the presence of novel sulfated peptides
      within the alpha-conotoxin molecular mass range in Conus anemone crude venom. A
      functional assay of the extract showed activity at several neuronal nicotinic
      acetylcholine receptors (nAChRs). Three sulfated alpha-conotoxins (AnIA, AnIB,
      and AnIC) were identified by LC/MS and assay-directed fractionation and sequenced
      after purification. The most active of these, alpha-AnIB, was further
      characterized and used to investigate the influence of posttranslational
      modifications on affinity. Synthetic AnIB exhibited subnanomolar potency at the
      rat alpha3beta2 nAChR (IC50 0.3 nM) and was 200-fold less active on the rat
      alpha7 nAChR (IC50 76 nM). The unsulfated peptide [Tyr16]AnIB showed a 2-fold and
      10-fold decrease in activities at alpha3beta2 (IC50 0.6 nM) and alpha7 (IC50 836
      nM) nAChR, respectively. Likewise, removal of the C-terminal amide had a greater
      influence on potency at the alpha7 (IC50 367 nM) than at the alpha3beta2 nAChR
      (IC50 0.5 nM). Stepwise removal of two N-terminal glycine residues revealed that
      these residues affect the binding kinetics of the peptide. Comparison with
      similar 4/7-alpha-conotoxin sequences suggests that residue 11 (alanine or
      glycine) and residue 14 (glutamine) constitute important determinants for
      alpha3beta2 selectivity, whereas the C-terminal amidation and sulfation at
      tyrosine-16 favor alpha7 affinity.

PMID- 14971904
TI  - Prediction of human volume of distribution values for neutral and basic drugs. 2.
      Extended data set and leave-class-out statistics.
AB  - We present an extension and confirmation of our previously published method (J.
      Med. Chem. 2002, 45, 2867-2876) for the prediction of volume of distribution (VD)
      in humans for neutral and basic compounds. It is based on two experimentally
      determined physicochemical parameters, ElogD(7.4) and f(i(7.4)), the latter being
      the fraction of compound ionized at pH 7.4, and on the fraction of free drug in
      plasma (fu). By regressing the fraction unbound in tissues, fut, vs the above
      parameters, we demonstrate the ruggedness of the method in predicting VD through
      the Oie-Tozer equation, via the use of several testing approaches. A comparison
      is also presented between several methods based on animal pharmacokinetic data,
      using the same set of proprietary compounds, and it lends further support for the
      use of this method, as opposed to methods that require the gathering of
      pharmacokinetic data in laboratory animals. The reduction in the use of animals
      and the overall faster and cheaper accessibility of the parameters used make this
      method highly attractive for prospectively predicting the VD of new chemical
      entities in humans.

PMID- 14971905
TI  - Design, synthesis, and evaluation of a liposaccharide drug delivery agent:
      application to the gastrointestinal absorption of gentamicin.
AB  - The design, synthesis, and evaluation of a liposaccharide (11) for use as an
      agent to enhance the gastrointestinal absorption of charged, hydrophilic drugs
      with poor membrane permeability is reported. 11 was designed to possess both
      surfactant and ion-pairing properties and was conveniently synthesized from d
      glucuronic acid (2) and N-Boc-lipoamino acid (5) precursors in eight steps in
      good yield. Isothermal titration microcalorimetry was used to determine the
      critical micelle concentration of 11 (in PBS) to be 2.09 +/- 0.01 mM with an
      enthalpy of demicellization of 4.91 +/- 0.11 kJ/mol. The ability of 11 to enhance
      the gastrointestinal absorption of the aminoglycoside antibiotic gentamicin (1),
      a hydrophilic polycation with negligible oral bioavailability, was assessed in
      vivo using rats. Rats dosed orally with a mixture of 11 (100 mg/kg) and 1 (60
      mg/kg) had a statistically significant (P < or = 0.034) increase in Cmax, AUC120,
      and percent absolute bioavailability (F) compared to control 1 (60 mg/kg) alone.
      The highest bioavailability (F = 9.1 +/- 2.0%) was achieved by dosing with the
      mixture 11 (100 mg/kg) and 1 (15 mg/kg). This represents a 6-fold increase in
      bioavailability compared to the control (F = 1.4 +/- 0.3%). These results suggest
      that the molar ratio of 1:11 may be critical in optimizing the delivery system, a
      finding ascribed in part to the ion-pairing properties of 11. The effect of 11 on
      the gastrointestinal mucosa was assessed using light microscopy to examine tissue
      samples from rats used in the pharmacokinetic study. No morphological changes
      were found in either the esophagi or duodena of the rats examined. One rat dosed
      with 11 (100 mg/kg) and 1 (60 mg/kg) exhibited slight gastric erosion, which
      could be attributed to 11.

PMID- 14971906
TI  - Synthesis and structure-activity relationships of 1-arylmethyl-5-aryl-6
      methyluracils as potent gonadotropin-releasing hormone receptor antagonists.
AB  - Based on the SAR from bicyclic gonadotropin-releasing hormone (GnRH) antagonists
      such as 6-aminomethyl-7-aryl-pyrrolo[1,2-a]pyrimid-4-ones (5) and 2-aryl-3
      aminomethyl-imidazolo[1,2-a]pyrimid-5-ones (6a,b), a series of novel uracil
      compounds (8) were derived as GnRH antagonists. The synthesis and SAR studies of
      6-methyluracils as human GnRH receptor antagonists are discussed herein.
      Introduction of a small methyl substituent at the beta-position of the N3 side
      chain improved the GnRH binding potency by 5-10-fold. Introduction of a methyl
      group of (R)-configuration at the alpha-carbon of the N-3 side-chain gave a
      modest improvement in binding affinity over the unsubstituted ethylene analogues.
      This modification enabled us to make uracil compounds without the labile 2
      pyridylethyl motif on the basic nitrogen while still maintained excellent potency
      against the hGnRH receptor.

PMID- 14971907
TI  - Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with
      aromatic and heterocyclic sulfonamides.
AB  - The first inhibition study of the mitochondrial isozyme carbonic anhydrase (CA) V
      (of murine origin) with a series of aromatic and heterocyclic sulfonamides is
      reported. Inhibition data of the cytosolic isozymes CA I and CA II and the
      membrane-bound isozyme CA IV with these inhibitors are also provided for
      comparison. Several low nanomolar CA V inhibitors were detected (KI values in the
      range of 4-15 nM), most of them belonging to the acylated sulfanilamide, ureido
      benzenesulfonamide, 1,3,4-thiadiazole-2-sulfonamide, and aminobenzolamide type of
      compounds. The clinically used inhibitors acetazolamide, methazolamide,
      ethoxzolamide, dorzolamide, brinzolamide, and topiramate on the other hand were
      less effective CA V inhibitors, showing inhibition constants in the range of 47
      63 nM. Some of the investigated sulfonamides, such as the ureido
      benzenesulfonamides and the acylated sulfanilamides showed higher affinity for CA
      V than for the other isozymes, CA II included, which is a remarkable result,
      since most compounds investigated up to now inhibited the cytosolic isozyme CA II
      better. These results prompt us to hypothesize that the selective inhibition of
      CA V, or the dual inhibition of CA II and CA V, may lead to the development of
      novel pharmacological applications for such sulfonamides, for example in the
      treatment or prevention of obesity, by inhibiting CA-mediated lipogenetic
      processes.

PMID- 14971908
TI  - Synthesis, characterization, and preliminary in vivo tests of new poly(ethylene
      glycol) conjugates of the antitumor agent 10-amino-7-ethylcamptothecin.
AB  - Despite the high antitumor activity of camptothecins, few derivatives have been
      developed and tested for human treatment of solid tumors, due to unpredictable
      toxicity mainly connected to their poor water solubility. We report the
      conjugation of the antitumor agent 10-amino-7-hydroxy camptothecin (SN-392) to
      linear or branched poly(ethylene glycol)s (PEGs) of different loading capacity
      through a tri- or tetrapeptide spacer selectively cleaved by lysosomal enzymes
      (cathepsins). A synthetic strategy based on the chemoselective acylation of the
      aromatic amino group in the presence of the unprotected C20 tertiary alcohol
      allowed high overall yields. Two conjugates demonstrated good stability at
      physiological pH and in mouse plasma (nonspecific proteases) but slowly released
      the drug payload in the presence of the lysosomal enzyme cathepsin B1. Compound
      3, selected for in vivo experiments, was very active against P388, P388/ADM
      leukaemia, and Meth A fibrosarcoma cell lines, scoring T/C% values comparable
      with the camptothecin derivative CPT-11. Pharmacokinetic studies indicated that 3
      acts as a reservoir of 10-amino-7-ethylcamptothecin, as the mean residence time
      (MRT) is about 3-fold higher than that of the free drug.

PMID- 14971909
TI  - Antimalarial and antitumor evaluation of novel C-10 non-acetal dimers of 10beta
      (2-hydroxyethyl)deoxoartemisinin.
AB  - Four series of C-10 non-acetal dimers were prepared from key trioxane alcohol
      10beta-(2-hydroxyethyl)deoxoartemisinin (9b). All of the dimers prepared
      displayed potent low nanomolar antimalarial activity versus the K1 and HB3
      strains of Plasmodium falciparum. The most potent compound assayed was phosphate
      dimer 14a, which was greater than 50 times more potent than the parent drug
      artemisinin and about 15 times more potent than the clinically used acetal
      artemether. In contrast to their potent activity versus malaria parasites,
      virtually all of the dimers expressed poor anticancer activity apart from the
      trioxane phosphate ester dimers 14a and 14b, which expressed nanomolar growth
      inhibitory (GI50) values versus a range of cancer cell lines in the NCI 60 human
      cell line screen. Further detailed studies on these dimers in vitro in HL60 cells
      demonstrate that both phosphate ester dimers (14a and 14b) are more potent than
      the anticancer agent doxorubicin. Interestingly, phosphate ester monomers 9c and
      9d, antimalarially active in the low nanomolar region versus P. falciparum, are
      inactive as anticancer agents even at concentrations in the millimolar region.
      This observation emphasizes the importance of two trioxane units for high
      antiproliferative activity, and we propose that the nature of the linker in
      dimers of this type plays a crucial role in imparting potent anticancer activity.

PMID- 14971910
TI  - Anticancer and antimalarial efficacy and safety of artemisinin-derived trioxane
      dimers in rodents.
AB  - In only four chemical steps from naturally occurring artemisinin (1), trioxane
      dimers 6 and 7 were prepared on a multigram scale in overall 32-44% yields. In
      mice, both isonicotinate N-oxide dimer 6 and isobutyric acid dimer 7 were
      considerably more antimalarially efficacious than clinically used sodium
      artesunate (2) via both oral and intravenous administration. In the transgenic
      adenocarcinoma of mouse prostate model, some of the trioxane dimers had potent
      anticancer activity.

PMID- 14971911
TI  - Terminal and four-coordinate vanadium(IV) phosphinidene complexes. A pseudo Jahn
      Teller effect of second order stabilizing the V-P multiple bond.
AB  - Treatment of the four-coordinate vanadium neopentylidene (Nacnac)V=CHtBu(I)
      (Nacnac- = [Ar]NC(Me)CHC(Me)N[Ar], Ar = 2,6-iPr2C6H3) with a bulky primary
      lithium phosphide LiPHR (R = 2,4,6-iPr3C6H2, 2,4,6-tBu3C6H2) leads to alpha
      hydrogen migration concomitant with the formation of a four-coordinate vanadium
      complex containing a terminal phosphinidene functionality (Nacnac)V=PR(CH2tBu).
      The crystal structures for the vanadium phosphinidene complexes prepared herein
      were determined by single-crystal X-ray diffraction methods. Solution EPR and
      magnetic measurements of the vanadium phosphinidenes are also in accordance with
      such systems containing a V(IV) metal center, and DFT calculations indicate the
      V=P bond to be stabilized through a pseudo Jahn-Teller effect of second order.

PMID- 14971912
TI  - Hybrid approach to the synthesis of highly luminescent CdTe/ZnS and CdHgTe/ZnS
      nanocrystals.
AB  - We report the synthesis of highly luminescent CdTe/ZnS and CdHgTe/ZnS core/shell
      semiconductor nanocrystals (NCs). A hybrid of two synthesis routes leads to novel
      nanocrystal compositions and small core/shell sizes (4-5 nm) that emit in the far
      red and near-infrared regions. These particles exhibit higher resistance to
      oxidation and photobleaching, have high quantum yields, and could be used for
      biological labeling and imaging.

PMID- 14971913
TI  - A combined density functional theory and molecular mechanics study of the
      relationship between the structure of coenzyme B12 and its binding to
      methylmalonyl-CoA mutase.
AB  - A combined density functional theory (DFT) and molecular mechanics (MM) approach
      was applied to investigate the relationship between the structure of a free
      coenzyme B12, and bound to methylmalonyl-CoA mutase. It was found that, upon
      coenzyme binding to apoenzyme, the Co-C bond remains intact, while the C-Naxial
      bond becomes slightly elongated and labilized. The labilization of the Co-Naxial
      bond that takes place in coenzyme B12-dependent enzymes is most likely necessary
      for fine-tuning of the cobalt-nitrogen (axial base) distance. The controlling of
      this distance is important to inhibit abiological site reaction involving
      heterolysis of the Co-C bond but is not important for biologically relevant Co-C
      bond homolysis.

PMID- 14971914
TI  - NO-bound myoglobin: structural diversity and dynamics of the NO ligand.
AB  - We used femtosecond infrared polarization spectroscopy and density functional
      theory in a study on the key signaling molecule nitric oxide (NO) bound to
      myoglobin. Our results show that after photolysis, a substantial fraction of NO
      recombines within the first few picoseconds. We discovered that the diatomic
      ligand is severely tilted in the protein and present evidence that the Fe-NO
      moiety can sample a wide range of off-axis tilting and bending conformations.

PMID- 14971915
TI  - Designed self-assembly of molecular necklaces using host-stabilized charge
      transfer interactions.
AB  - A novel approach to the noncovalent synthesis of molecular necklaces successfully
      led to the first quantitative self-assembly of a molecular necklace [6]MN, in
      which five small rings are threaded on a large ring, from 10 components. Our
      strategy involves the host-guest complex formation between the molecular host
      cucurbit[8]uril (CB[8]) and a guest molecule in which an electron donor and an
      electron acceptor unit are connected by a rigid linker with a proper angle, to
      form a cyclic oligomer through the host-stabilized intermolecular charge-transfer
      (CT) complex formation. In the structure of the molecular necklace [6]MN, five
      molecules of the guest form a cyclic framework by the intermolecular CT
      interactions, on which five CB[8] molecules are threaded with an arrangement
      reminiscent of a five-fold propeller. The molecular necklace measures
      approximately 3.7 nm in diameter and approximately 1.8 nm in thickness.

PMID- 14971916
TI  - Marked increase in the binding strength between the substrate and the covalently
      attached monolayers of zeolite microcrystals by lateral molecular cross-linking
      between the neighboring microcrystals.
AB  - Monolayers of cubic zeolite microcrystals (1.7 x 1.7 x 1.7 and 0.3 x 0.3 x 0.3
      mum3) were assembled on glass plates through imine- or urethane-linkages between
      the zeolite-tethered 3-aminopropyl (AP) groups and the glass-bound benzaldehyde
      or isocyanate groups, which were prepared by treating AP-tethering glass plates
      with a large excess of terephthaldicarboxaldehyde (TPDA) or 1,4
      diisocyanatobutane (DICB), respectively, in toluene. The additional treatment of
      the monolayers of zeolite microcrystals with TPDA or DICB led to lateral
      molecular cross-linking between the neighboring, closely packed zeolite
      microcrystals in the monolayers through AP-TPDA-AP imine or AP-DICB-AP urethane
      linkages between the zeolite-tethered AP groups and the newly introduced TPDA or
      DICB, respectively. The comparison of the binding strengths between the glass
      substrates and the monolayers revealed that the molecular cross-linking leads to
      as much as 7- and 38-fold (by average) increase in the binding strength in the
      cases of 1.7 x 1.7 x 1.7 and 0.3 x 0.3 x 0.3 mum3 crystals, respectively. We
      predict that the effect of lateral cross-linking on the binding strength will
      further increase with further decreasing the size of the building blocks to
      nanoparticles and to molecules.

PMID- 14971917
TI  - Micellar affinity gradient focusing: a new method for electrokinetic focusing.
AB  - This report describes a new method for the concentration and separation of
      neutral and/or hydrophobic analytes based on a combination of the analytes'
      electrophoretic mobility, and affinity for partitioning into a micellar phase.
      Micellar affinity gradient focusing (MAGF) works by creating a gradient in the
      micellar retention factor. An electric field is applied along the channel to
      cause the (negatively charged) micelles to move from the region of high retention
      to the region of low retention, and the mobile phase is forced to move from the
      region of low retention to the region of high retention. Consequently, the
      analyte moves into the gradient region from both directions where it is
      concentrated at a point where its total velocity is zero. Different analytes,
      which interact differently with the micelles, will have zero total velocity at
      different points along the gradient, and will thereby be simultaneously
      concentrated and separated.

PMID- 14971918
TI  - Periodicity in residual dipolar couplings and nucleic acid structures.
AB  - The periodicity in nucleic acid duplex structures is shown to be correlated to
      the periodicity in residual dipolar couplings (RDCs) in the form of an "RDC
      wave". This "RDC wave" is characteristic of the alignment of the duplex in the
      magnetic field, and hence fitting of the data allows the duplex global
      orientation (, Phi) to be extracted. Further, because the "RDC wave" is fit as a
      data set of a corresponding secondary structure element, the degeneracy problem
      is greatly reduced. Consequently, with the global orientation (, Phi) determined,
      local bond vector conformations are defined. The fit is demonstrated in the
      examples of the imino RDCs of the negative regulator of splicing RNA fragment
      (NRS23) and for the C1'H1' RDCs of the Dickerson dodecamer.

PMID- 14971919
TI  - Electrostatic control of the regioselectivity in the photoisomerization of
      trans,trans-1-fluoro-2,4-hexadiene: evidence for competing conical intersections.
AB  - trans,trans-1-Fluoro-2,4-hexadiene (EE-FHD) was used to explore the excited
      potential energy surfaces of acyclic 1,3-dienes. Our investigations show that the
      regioselectivity of double-bond photoisomerization is primarily controlled by the
      charge-stabilizing characteristic of substituents on the double bonds of the
      diene. Furthermore, changes in the photoregioselectivity with solvent polarity
      suggest that the excited unsymmetrical diene returns to the ground state by
      competing pathways which traverse polarized 1Bu states and drop into two
      different conical intersections

PMID- 14971920
TI  - Interpolyelectrolyte complexes of conjugated copolymers and DNA: platforms for
      multicolor biosensors.
AB  - Interchain interactions modulate the frequency of emission from a cationic water
      soluble conjugated polymer. The polymer, PFPB, is obtained by a Suzuki
      copolymerization of p-phenylenebisboronic acid with a 95:5 mixture of 2,7-dibromo
      9,9-bis(6'-bromohexyl)fluorene and 4,7-dibromo-2,1,3-benzothiadiazole, followed
      by quarternization of the pendant groups by addition of NMe3. The structure of
      PFPB contains 5% of the 2,1,3-benzothiadiazole (BT) chromophore within a cationic
      poly(fluorene-co-phenylene) polymer chain. The emission of PFPB is blue under
      dilute conditions (<1 x 10-6 M in repeat units) and green at higher
      concentrations. Energy transfer to dye-labeled ss-DNA is more efficient, relative
      to the parent polymer poly(9,9-bis(6'-N,N,N,-trimethylammonium)hexyl)fluorene-co
      alt-1,4-phenylene) dibromide (PFP), as a result of improved spectral overlap. By
      using a peptide nucleic acid (PNA-C*) labeled with a red-emitting chromophore one
      can obtain three different emission colors, depending on the nature of the
      substrate under interrogation. If no ss-DNA is present, the solution emits blue.
      With a ss-DNA that is noncomplementary to PNA-C*, green emission is observed. Red
      emission occurs upon addition of ss-DNA complementary to the PNA sequence.

PMID- 14971921
TI  - 5H-oxazol-4-ones as building blocks for asymmetric synthesis of alpha
      hydroxycarboxylic acid derivatives.
AB  - 5H-Alkyl-2-phenyl-oxazol-4-ones, a little-known heterocyclic ring system, are
      readily available via a microwave-assisted, sodium fluoride catalyst cyclization
      of mono-alpha-haloimides, which in turn are accessed by N-acylation of benzamides
      with alpha-bromo acid halides. Terminally substituted allyl systems serve as
      excellent substrates for Mo-catalyzed asymmetric allylic alkylation. The
      resultant products are formed with excellent ees involving a catalyst derived
      from N,N'-bis-picolinamide of trans-1,2-diaminocyclohexane and cycloheptatriene
      molybdenum tris(carbonyl). In addition to benzenoid, nonbenzenoid aromatic and
      vinyl substituents on the allyl carbonate moiety provide good to excellent regio-
      and diastereoselectivity as well as excellent enantioselectivity. Substituents on
      the heterocycle include methyl, n-butyl, allyl, isobutyl, isopropyl, and
      cyclohexyl. The presence of a double bond in the product allows them to be
      further modified via the chemistry of the double-bond, including metathesis. The
      products are hydrolyzed under basic conditions to provide alpha-hydroxyamides.

PMID- 14971922
TI  - Preparation and characterization of an isometallabenzene with the structure of a
      1,2,4-cyclohexatriene.
AB  - The elongated dihydrogen complex [Os{C6H4C(O) CH3}(eta2-H2)(H2O)(PiPr3)2]BF4
      reacts with phenylacetylene and HBF4.OEt2 to give the unsaturated compound
      [Os{(E)-CH=CHPh}(CCPh)(CCH2Ph)(PiPr3)2]BF4 containing alkenyl, alkynyl, and
      carbyne ligands. The addition of sodium chloride to this compound leads to the
      cyclic allene Os{=C=C(Ph)CH(Ph)CH=C(CH2Ph)}Cl(PiPr3)2, which is the first
      isometallabenzene with the structure of a 1,2,4-cyclohexatriene.

PMID- 14971923
TI  - Catalytic homologation of vinyltributylstannane to allyltributylstannane by
      Mo(IV) complexes in the presence of ethylene.
AB  - We have found that CH2=CHSnBu3 is converted into CH2=CHCH2SnBu3 catalytically in
      the presence of Mo(IV) olefin complexes such as Mo(NAr)(CH2CH2)[biphen] (where Ar
      = 2,6-i-Pr2C6H3 and [biphen]2- = 3,3'-di-tert-butyl-5,5',6,6'-tetramethyl-1,1'
      biphenyl-2,2'-diolate). The proposed mechanism involves formation of a
      metalacyclopentane (MC4) complex from ethylene and CH2=CHSnBu3, "contraction" of
      this MC4 complex to a metalacyclobutane (MC3) complex, and finally metathesis of
      the MC3 complex to give CH2=CHCH2SnBu3 and Mo(NAr)(CH2)[biphen]. These new
      findings suggest (inter alia) that contraction of an MC4 ring to an MC3 ring may
      be a much more common mode of decomposition of metalacyclopentane rings in d0
      complexes than previously believed.

PMID- 14971924
TI  - Shape evolution of single-crystalline iron oxide nanocrystals.
AB  - Shape- and size-controlled synthesis of single-crystalline maghemite (gamma
      Fe2O3) nanocrystals are performed by utilizing a solution-based one-step
      thermolysis method. Modulating the growth parameters, such as the type and amount
      of capping ligands as well as the growth time, is shown to have a significant
      effect on the overall shape and size of the obtained nanocrystals and on the
      ripening process itself. The resulting shapes of the novel structures are
      diverse, including slightly faceted spheres, diamonds, prisms, and hexagons, all
      of which are in fact truncated dodecahedron structures with different degrees of
      truncation along the {111}, {110}, or {100} faces. Spherical nanocrystals are
      easily assembled into the three-dimensional superlattices, demonstrating the
      uniformity of these nanocrystals. The size-dependent magnetic properties are
      examined, and large hexagon-shaped gamma-Fe2O3 nanocrystals are shown to be
      ferrimagnetic at room temperature.

PMID- 14971925
TI  - The assignment of downfield proton resonances in an enzyme inhibitor complex
      using time-dependent saturation transferred NOEs.
AB  - We have used time-dependent saturation transferred NOE (STNOE) measurements to
      assign two downfield resonances in the proton spectrum of an adenosine deaminase
      purine riboside mixture. Our results show that this method can be used to detect
      structural changes that occur upon inhibitor binding to the enzyme and to
      determine which protons of the bound inhibitor are strongly hydrogen bonded in
      the complex.

PMID- 14971926
TI  - Construction of arene-fused-piperidine motifs by asymmetric addition of 2
      trityloxymethylaryllithiums to nitroalkenes: the asymmetric synthesis of a
      dopamine D1 full agonist, A-86929.
AB  - The straightforward methodology for the construction of chiral arene-fused
      piperidine motifs using a highly enantioselective addition of 2
      trityloxymethylaryllithiums to cyclic and acyclic nitroalkenes has been
      developed. The versatility of the process was highlighted by the first asymmetric
      synthesis of a dopamine D1 full agonist, A-86929.

PMID- 14971927
TI  - An approach to enhance specificity against RNA targets using heteroconjugates of
      aminoglycosides and chloramphenicol (or linezolid).
AB  - We describe the design and synthesis of new heterodimeric conjugates, which are
      comprised of a neomycin B (Neo) stem-binding component and a chloramphenicol
      (Cam) or linezolid (Lnz) loop-binding component. Some of the heterodimeric
      conjugates display enhanced affinities to RNA targets and that binding occurs in
      both stem and loop regions of the RNA. In addition, the results of foot-printing
      and mutation studies suggest that the enhanced binding affinity of the conjugates
      is RNA sequence-specific.

PMID- 14971928
TI  - Impact of protein denaturants and stabilizers on water structure.
AB  - It is of great interest to determine how solutes such as urea, sugars,
      guanidinium salts, and trimethylamine N-oxide affect the stability, solubility,
      and solvation of globular proteins. A key hypothesis in this field states that
      solutes affect protein stability indirectly by making or breaking water
      structure. We used a new technique, pressure perturbation calorimetry, to measure
      the temperature dependence of a solute's partial compressibility. Using
      fundamental thermodynamic relations, we converted these data to the pressure
      dependence of the partial heat capacity to examine the impact of protein
      stabilizing and denaturing solutes on water structure by applying the classic two
      state mixture model for water. Contrary to widely held expectations, we found no
      correlation between a solute's impact on water structure and its effect on
      protein stability. Our results indicate that efforts to explain solute effects
      should focus on other hypotheses, including those based on preferential
      interaction and excluded volume.

PMID- 14971929
TI  - Determination of the glycosidic bond angle chi in RNA from cross-correlated
      relaxation of CH dipolar coupling and N chemical shift anisotropy.
AB  - A new heteronuclear NMR pulse sequence, the quantitative Gamma(HCN) experiment,
      for the determination of the glycosidic torsion angle chi in (13)C,(15)N-labeled
      oligonucleotides is described. The Gamma(HCN) experiment allows measurement of CH
      dipole-dipole, N chemical shift anisotropy cross-correlated relaxation rates
      (Gamma(C1'H1',N1)(DD,CSA) and Gamma(C2'H2',N9)(DD,CSA) for pyrimidines
      Gamma(C1'H1'N9)(DD,CSA) and Gamma(C2'H2',N9)(DD,CSA) for purines). A nucleotide
      specific parametrization for the dependence of these Gamma-rates on chi based on
      (15)N chemical shift tensors determined by solid-state NMR experiments on
      mononucleosides (Stueber, D.; Grant, D. M. J. Am. Chem. Soc. 2002, 124, 10539
      10551) is presented. For a 14-mer and a 30-mer RNA of known structures, it is
      found that the Gamma(HCN) experiment offers a very sensitive parameter for
      changes in the angle chi and allows restraining of chi with an accuracy of around
      10 degrees for residues which do not undergo conformational averaging. Therefore,
      the Gamma(HCN) experiment can be used for the determination of chi in addition to
      data derived from (3)J(C,H)-coupling constants. As shown for the 30-mer RNA, the
      derived torsion angle information can be incorporated as additional restraint,
      improving RNA structure calculations.

PMID- 14971930
TI  - Cyclic amidine sugars as transition-state analogue inhibitors of glycosidases:
      potent competitive inhibitors of mannosidases.
AB  - A series of monocyclic glycoamidines bearing different exocyclic amine, alcohol,
      or alkyl functionalities and bicyclic amidines derived from D-glucose and D
      mannose were synthesized and tested as inhibitors of various glycosidases. All
      the prepared compounds demonstrated good to excellent inhibition toward
      glycosidases. In particular, the biscationic D-mannoamidine 9b bearing an
      exocyclic ethylamine moiety proved to be a selective competitive inhibitor of
      alpha- and beta-mannosidases (K(i) = 6 nM) making it the most potent inhibitor of
      these glycosidases reported to date. A favorable B(2,5) boat conformation might
      explain the selectivity of mannosidase inhibition compared to other glycosidases.

PMID- 14971931
TI  - Electronically driven structural distortions in lithium intercalates of the n = 2
      Ruddlesden-Popper-type host Y2Ti2O5S2: synthesis, structure, and properties of
      LixY2Ti2O5S2 (0 < x < 2).
AB  - Lithium intercalation into the oxide slabs of the cation-deficient n = 2
      Ruddlesden-Popper oxysulfide Y(2)Ti(2)O(5)S(2) to produce Li(x)Y(2)Ti(2)O(5)S(2)
      (0 < x < 2) is described. Neutron powder diffraction measurements reveal that at
      low levels of lithium intercalation into Y(2)Ti(2)O(5)S(2), the tetragonal
      symmetry of the host is retained: Li(0.30(5))Y(2)Ti(2)O(5)S(2), I4/mmm, a =
      3.80002(2) A, c = 22.6396(2) A, Z = 2. The lithium ion occupies a site
      coordinated by four oxide ions in an approximately square planar geometry in the
      perovskite-like oxide slabs of the structure. At higher levels of lithium
      intercalation, the symmetry of the cell is lowered to orthorhombic:
      Li(0.99(5))Y(2)Ti(2)O(5)S(2), Immm, a = 3.82697(3) A, b = 3.91378(3) A, c =
      22.2718(2) A, Z = 2, with ordering of Li(+) ions over two inequivalent sites. At
      still higher levels of lithium intercalation, tetragonal symmetry is regained:
      Li(1.52(5))Y(2)Ti(2)O(5)S(2), I4/mmm, a = 3.91443(4) A, c = 22.0669(3) A, Z = 2.
      A phase gap exists close to the transition from the tetragonal to orthorhombic
      structures (0.6 < x < 0.8). The changes in symmetry of the system with electron
      count may be considered analogous to a cooperative electronically driven Jahn
      Teller type distortion. Magnetic susceptibility and resistivity measurements are
      consistent with metallic properties for x > 1, and the two-phase region is
      identified as coincident with an insulator to metal transition.

PMID- 14971932
TI  - Solution NMR studies of the A beta(1-40) and A beta(1-42) peptides establish that
      the Met35 oxidation state affects the mechanism of amyloid formation.
AB  - The pathogenesis of Alzheimer's disease is characterized by the aggregation and
      fibrillation of the 40-residue A beta(1-40) and 42-residue A beta(1-42) peptides
      into amyloid plaques. The structural changes associated with the conversion of
      monomeric A beta peptide building blocks into multimeric fibrillar beta-strand
      aggregates remain unknown. Recently, we established that oxidation of the
      methionine-35 side chain to the sulfoxide (Met35(red) --> Met35(ox))
      significantly impedes the rate of aggregation and fibrillation of the A beta
      peptide. To explore this effect at greater resolution, we carefully compared the
      (1)H, (15)N, and (13)C NMR chemical shifts of four A beta peptides that had the
      Met35 reduced or oxidized (A beta(1-40)Met35(red), A beta(1-40)Met35(ox), A
      beta(1-42)Met35(red), and A beta(1-42)Met35(ox)). With the use of a special
      disaggregation protocol, the highly aggregation prone A beta peptides could be
      studied at higher, millimolar concentrations (as required by NMR) in aqueous
      solution at neutral pH, remaining largely monomeric at 5 degrees C as determined
      by sedimentation equilibrium studies. The NOE, amide-NH temperature coefficients,
      and chemical shift indices of the (1)H alpha, (13)C alpha, and (13)C beta
      established that the four peptides are largely random, extended chain structures,
      with the Met35(ox) reducing the propensity for beta-strand structure at two
      hydrophobic regions (Leu17-Ala21 and Ile31-Val36), and turn- or bendlike
      structures at Asp7-Glu11 and Phe20-Ser26. Additional NMR studies monitoring
      changes that occur during aging at 37 degrees C established that, along with a
      gradual loss of signal/noise, the Met35(ox) significantly hindered upfield
      chemical shift movements of the 2H NMR signals for the His6, His13, and His14
      side chains. Taken together, the present NMR studies demonstrate that the
      Met35(red) --> Met35(ox) conversion prevents aggregation by reducing both
      hydrophobic and electrostatic association and that the A beta(1-40)Met35(red), A
      beta(1-40)Met35(ox), A beta(1-42)Met35(red), and A beta(1-42)Met35(ox) peptides
      may associate differently, through specific, sharp changes in structure during
      the initial stages of aggregation.

PMID- 14971933
TI  - Interaction between non-heme iron of lipoxygenases and cumene hydroperoxide:
      basis for enzyme activation, inactivation, and inhibition.
AB  - Lipoxygenase catalysis depends in a critical fashion on the redox properties of a
      unique mononuclear non-heme iron cofactor. The isolated enzyme contains
      predominantly, if not exclusively, iron(II), but the catalytically active form of
      the enzyme has iron(III). The activating oxidation of the iron takes place in a
      reaction with the hydroperoxide product of the catalyzed reaction. In a second
      peroxide-dependent process, lipoxygenases are also inactivated. To examine the
      redox activation/inactivation dichotomy in lipoxygenase chemistry, the
      interaction between lipoxygenase-1 (and -3) and cumene hydroperoxide was
      investigated. Cumene hydroperoxide was a reversible inhibitor of the reaction
      catalyzed by lipoxygenase-1 under standard assay conditions at high substrate
      concentrations. Reconciliation of the data with the currently held kinetic
      mechanism requires simultaneous binding of substrate and peroxide. The enzyme
      also was both oxidized and largely inactivated in a reaction with the peroxide in
      the absence of substrate. The consequences of this reaction for the enzyme
      included the hydroxylation at C beta of two amino acid side chains in the
      vicinity of the cofactor, Trp and Leu. The modifications were identified by mass
      spectrometry and X-ray crystallography. The peroxide-induced oxidation of iron
      was also accompanied by a subtle rearrangement in the coordination sphere of the
      non-heme iron atom. Since the enzyme retains catalytic activity, albeit
      diminished, after treatment with cumene hydroperoxide, the structure of the iron
      site may reflect the catalytically relevant form of the cofactor.

PMID- 14971934
TI  - Heat-set gel-like networks of lipophilic Co(II) triazole complexes in organic
      media and their thermochromic structural transitions.
AB  - A novel class of thermally responsive supramolecular assemblies is formed from
      the lipophilic cobalt(II) complexes of 4-alkylated 1,2,4-triazoles. When an ether
      linkage is introduced in the alkylchain moiety, a blue gel-like phase is formed
      in chloroform, even at very low concentration (ca. 0.01 wt %, at room
      temperature). The blue color is accompanied by a structured absorption around 580
      730 nm, which is characteristic of cobalt (II) in the tetrahedral (T(d))
      coordination. Atomic force microscopy (AFM) and transmission electron microscopy
      (TEM) of the gel-like phase confirms the formation of networks of fibrous
      nanoassemblies with widths of 5-30 nm. The observed widths are larger than a
      molecular length of the triazole ligand (ca. 2.2 nm) and they are consisted of
      aggregates of T(d) coordination polymers. Very interestingly, the blue gel-like
      phase turned into a solution by cooling below 25 degrees C. A pale pink solution
      is obtained at 0 degrees C, indicating the formation of octahedral (O(h))
      complexes. The observed thermochromic transition is totally reversible. The
      formation of gel-like networks by heating is contrary to the conventional
      organogels, which dissolve upon heating. Temperature dependence of the storage
      and loss moduli (G' and G") shows minima around at 27 degrees C, at which
      temperature they gave comparable values. On the other hand, G' exceeds G" both in
      the gel-like phase (temperature above 27 degrees C) and in the solution phase
      (temperature below 25 degrees C). These observations indicate that T(d) complexes
      are present as low-molecular weight species around at 25-27 degrees C. They are
      self-assembled to polymeric T(d) complexes by heating and form gel-like networks.
      Upon cooling the solution below 25 degrees C, T(d) complexes are converted to
      O(h) complexes and they also self-assemble into oligomeric or polymeric species
      at lower temperatures. The observed unique thermochromic transition (pink
      solution --> blue gel-like phase) is accompanied by an exothermic peak in
      differential scanning calorimetry (DSC), and is shown to be an enthalpy-driven
      process. The lipophilic modification of one-dimensional coordination systems
      provides unique solution properties and it would be widely applicable to the
      design of thermoresponsive, self-assembling molecular wires.

PMID- 14971935
TI  - Saccharide-dependent induction of chiral helicity in achiral synthetic hydrogen
      bonding oligomers.
AB  - Conformational transitions of biopolymers are well-known to be affected by
      noncovalent interactions with small molecules. We found that synthetic polymers,
      poly- and oligo(meta-ethynylpyridine)s, are guided to helical structures by
      uncharged hydrogen-bonding interactions with saccharides enclosed in the inner
      sphere of the polymers. Circular dichroism (CD) studies revealed that chirality
      of saccharide was transferred to the helical sense of the polymers. Among the n
      octyl pyranosides of naturally important hexoses, beta-glucoside induced CDs most
      effectively. Size-regulated 18-mer and longer oligomers also showed the induced
      CDs similar to those for the polymers. Furthermore, native monosaccharides were
      extracted into less polar organic solvent with the help of the polymers, inducing
      similar CD signals.

PMID- 14971936
TI  - Comparison of C-H...pi and hydrophobic interactions in a beta-hairpin peptide:
      impact on stability and specificity.
AB  - We have examined the impact of C-H...pi and hydrophobic interactions in the
      diagonal position of a beta-hairpin peptide through comparison of the interaction
      of Phe, Trp, or Cha (cyclohexylalanine) with Lys or Nle (norleucine). NMR
      studies, including NOESY and chemical shift perturbation studies, of the Lys side
      chain indicates that Lys interacts in a specific geometry with Phe or Trp through
      the polarized C epsilon. In contrast, Nle does not interact in a specific manner
      with the diagonal aromatic residue. Thermal denaturation provides additional
      support that Lys and Nle interact in fundamentally different manners. Folding of
      the peptide with a diagonal Trp...Lys interaction was found to be enthalpically
      driven, whereas the peptide with a diagonal Trp...Nle interaction displayed cold
      denaturation, as did the control peptide with a diagonal Cha...Nle interaction,
      indicating different driving forces for interaction of Lys and Nle with Trp.
      These findings have significant implications for specificity in protein folding
      and de novo protein design.

PMID- 14971937
TI  - Crystal structures and topochemical polymerizations of 7,7,8,8
      tetrakis(alkoxycarbonyl)quinodimethanes.
AB  - Highly conjugated monomers, 7,7,8,8-tetrakis(alkoxycarbonyl)quinodimethanes
      (methoxy (1a), ethoxy (1b), isopropoxy (1c), benzyloxy (1d), chloroethoxy (1e),
      and bromoethoxy (1f)), were synthesized. Recrystallizations of 1a, 1c, 1e, and 1f
      yielded two crystal forms (prisms (1a-A) and needles (1a-B), needles (1c-A) and
      plates (1c-B), prisms (1e-A) and plates (1e-B), and prisms (1f-A) and needles (1f
      B)), which have different molecular packing modes by X-ray crystal structure
      analysis, indicating that the crystals are polymorphic. In the
      photopolymerizations of these monomer crystals in the solid state, 1a-A, 1e-A,
      and 1f-A polymerized topochemically to give crystalline polymers. For their
      thermal polymerizations in the solid state, in addition to 1a-A, 1e-A, and 1f-A,
      1e-B and 1f-B polymerized, but polymers formed from the 1e-B and 1f-B were
      amorphous. The packing of quinodimethane molecules in the crystals was defined by
      four kinds of parameters, stacking distance (d(s)), the distance between the
      reacting exomethylene carbon atoms (d(cc)), the angles formed between the
      stacking axis and longer axis of the monomer molecule (theta(1)), and the shorter
      axis of the monomer molecule (theta(2)), and then the polymerization reactivity
      of these quinodimethanes in the solid state was discussed on the basis of these
      parameters.

PMID- 14971938
TI  - Noncovalent interactions: defining cooperativity. Ligand binding aided by reduced
      dynamic behavior of receptors. Binding of bacterial cell wall analogues to
      ristocetin A.
AB  - Changes in the relative populations of the monomer and asymmetric dimer forms of
      ristocetin A, upon binding of two molecules of ligand, suggest that ligand
      binding is negatively cooperative with respect to dimerization. However, strong
      hydrogen bonds formed in the binding sites of the ligands are reinforced in the
      dimer relative to the monomer, and the barrier to dissociation of the dimer is
      increased upon binding of the ligands. It is concluded that the interactions
      which are common in the binding of both ligands are made with positive
      cooperativity with respect to those involved in dimerization. The conclusions are
      relevant to the binding of ligands to proteins, where ligand binding energy can
      be derived from stabilization of the protein in its ligand-bound form.

PMID- 14971939
TI  - Four-arm oligonucleotide Ni(II)-cyclam-centered complexes as precursors for the
      generation of supramolecular periodic assemblies.
AB  - The development of a multiarm metal-centered DNA building block as a precursor
      for the construction of supramolecular assemblies has relied upon the preparation
      of a Ni(II)-1,4,8,11-tetrazacyclotetradecane ligand (cyclam) functionalized with
      four linkers. This complex can be incorporated into a support-bound DNA sequence
      and the remaining three linkers can then be elongated by DNA synthesis. The
      result is a Ni(II)-cyclam complex tethering four 20-mer DNA strands. This
      building block, designed to be tetrahedral in nature, can in principle be used to
      form tetrahedral assemblies. These assemblies can be designed to be of known size
      and composition or permitted to grow into complexes of essentially infinite size,
      ideally the macroscopic version of a crystal.

PMID- 14971940
TI  - Modular domain structure: a biomimetic strategy for advanced polymeric materials.
AB  - A long lasting challenge in polymer science is to design polymers that combine
      desired mechanical properties such as tensile strength, fracture toughness, and
      elasticity into one structure. A novel biomimetic modular polymer design is
      reported here to address this challenge. Following the molecular mechanism used
      in nature, modular polymers containing multiple loops were constructed by using
      precise and strong hydrogen bonding units. Single-molecule force-extension
      experiments revealed the sequential unfolding of loops as a chain is stretched.
      The excellent correlation between the single-molecule and the bulk properties
      successfully demonstrates our biomimetic concept of using modular domain
      structure to achieve advanced polymer properties.

PMID- 14971941
TI  - Catalyst-nanostructure interfacial lattice mismatch in determining the shape of
      VLS grown nanowires and nanobelts: a case of Sn/ZnO.
AB  - Vapor-liquid-solid (VLS) is a well-established process in catalyst-guided growth
      of nanowires. The catalyst particle is generally believed to be in liquid state
      during growth, and it is the site for adsorbing incoming molecules; the
      crystalline structure of the catalyst may not have any influence on the structure
      of the grown one-dimensional nanostructures. In this paper, using tin particle
      guided growth of ZnO nanostructures as a model system, we show that the
      interfacial region of the tin particle with the ZnO nanowire/nanobelt could be
      ordered (or partially crystalline) during the VLS growth, although the local
      growth temperature is much higher than the melting point of tin, and the
      crystallographic lattice structure at the interface is important in defining the
      structural characteristics of the grown nanowires and nanobelts. The interface
      prefers to take the least lattice mismatch; thus, the crystalline orientation of
      the tin particle may determine the growth direction and the side surfaces of the
      nanowires and nanobelts. This result may have important impact on the
      understanding of the physical chemical process in the VLS growth.

PMID- 14971942
TI  - Selective metallic tube reactivity in the solution-phase osmylation of single
      walled carbon nanotubes.
AB  - Single-walled carbon nanotubes have been reacted with osmium tetroxide (OsO(4))
      in solution in the presence of O(2) and UV irradiation at 254 nm. We observe one
      main structural motif, namely thickly coated nanotube structures, densely covered
      with OsO(2), consisting of multiple bundles of derivatized tubes. In a few
      instances, bridging uncoated tubes, connecting these thickly coated structures,
      incorporate a number of smaller nanotube bundles, projecting out from the larger
      functionalized aggregates of tubes. It is believed that OsO(2) (a) initially
      forms on the nanotubes by the preferential covalent sidewall functionalization of
      metallic nanotubes and (b) subsequently self-aggregates. The formation of an
      intermediate charge-transfer complex is likely the basis for the observed
      selectivity and reactivity of metallic tubes. Extensive characterization of these
      osmylated adducts has been performed using a variety of electron microscopy and
      optical spectroscopy techniques.

PMID- 14971943
TI  - A concept for controlling singlet oxygen (1 Delta g) yields using nitroxide
      radicals: phthalocyaninatosilicon covalently linked to nitroxide radicals.
AB  - In this study, we have investigated the singlet oxygen ((1)Delta(g)) generation
      mechanism using phthalocyaninatosilicon (SiPc) covalently linked to nitroxide
      radicals (NRs), and we succeeded in increasing the singlet oxygen quantum yield
      (Phi(Delta)) by linking the NRs. This originates from both an increase in the
      triplet quantum yield and excited-state lifetimes long enough to utilize
      photochemical reactions. Because the electron exchange interactions with
      paramagnetic species were known to result only in very fast excited-state
      relaxation, leading to a decrease in photochemical reaction yields, this increase
      in Phi(Delta) is an unusual and precious example for increasing photochemical
      reaction yields by electron exchange interactions with paramagnetic species. In
      addition, our experiments and theoretical analyses show that the spin-selective
      energy transfer rate constant is not influenced by linking the NRs and can be
      evaluated by the product of spin-statistical factors and matrix elements between
      the initial and final states.

PMID- 14971944
TI  - (Butadiene)metallocene/B(C6F5)3 pathway to catalyst systems for stereoselective
      methyl methacrylate polymerization: evidence for an anion dependent metallocene
      catalyzed polymerization process.
AB  - The ansa-zirconocene dichlorides [Me(2)Si(C(5)H(4))(3-R-C(5)H(3))]ZrCl(2) 7a-e (R
      = H, CH(3), cyclohexyl, -CHMe(2), -CMe(3)) were reacted with butadiene-magnesium
      to yield the respective (eta(4)-butadiene)metallocenes 17a-e. The chiral examples
      give a mixture of two s-cis and two s-trans diastereomers. The strong Lewis acid
      B(C(6)F(5))(3) adds selectively to a terminal butadiene carbon atom to yield the
      (butadiene)metallocene/B(C(6)F(5))(3) betaine complexes 18a-e. Initially, the
      formation of the Z-18 isomers is preferred. These consecutively rearrange to the
      thermodynamically favored isomers E-18. The dipolar systems 18 are active single
      component metallocene catalysts for the stereospecific polymerization of methyl
      methacrylate. With increasing steric bulk of the attached single alkyl
      substituent an increasingly isotactic poly(methyl methacrylate) is obtained. A
      similar trend is observed in the methyl methacrylate polymerization at the
      [Me(2)Si(C(5)H(4))(3-R-C(5)H(3))]ZrCH(3)(+) catalysts (9a-e) that were
      conventionally prepared by methyl abstraction from the corresponding ansa
      zirconocene dimethyl complexes by treatment with B(C(6)F(5))(3). A comparison of
      the poly(methyl methacrylates) obtained at these two series of catalysts has
      revealed substantial differences in stereoselectivity that probably originate
      from an influence of the respective counteranions. An initial reactive
      intermediate of methyl methacrylate addition to the dipolar single component
      metallocene catalyst E-18a was experimentally observed and characterized by NMR
      spectroscopy at 253 K. The subsequently formed series of [PMMA-C(4)H(6)(
      )B(C(6)F(5))(3)](-) anion oligomers (at the catalyst 18c) was monitored (after
      quenching) and characterized by electrospray mass spectrometry.

PMID- 14971945
TI  - Aromatic vs aliphatic C-H cleavage of alkyl-substituted pyridines by (PNPiPr)Re
      compounds.
AB  - Both (PNP)Re(H)(4) and (PNP)ReH(cyclooctyne) (PNP(i)(Pr) =
      ((i)Pr(2)PCH(2)SiMe(2))(2)N) react with alkylpyridines NC(5)H(4)R to give first
      (PNP)ReH(2)(eta(2)-pyridyl) and cyclooctene and then, when not sterically
      blocked, (PNP)Re(eta(2)-pyridyl)(2) and cyclooctane. The latter are shown by NMR,
      X-ray diffraction, and DFT calculations to have several energetically competitive
      isomeric structures and pyridyl N donation in preference to PNP amide pi
      donation. DFT studies support NMR solution evidence that the most stable bis
      pyridyl structure is one that is doubly eta(2)- with the pyridyl N donating to
      the metal center. When both ortho positions carry methyl substituents,
      cyclooctane and the carbyne complex (PNP)ReH(tbd1;C-pyridyl) are produced. Excess
      2-vinyl pyridine reacts with (PNP)Re(H)(4) preferentially at the vinyl group, to
      give 2-ethyl pyridine and the sigma-vinyl complex (PNP)ReH[eta(2)-CH=CH(2-py)].
      The DFT and X-ray structures show, by various comparisons, the ability of the PNP
      amide nitrogen to pi-donate to an otherwise unsaturated d(4) Re(III) center,
      showing short Re-N distances consistent with the presence of pi-donation.

PMID- 14971946
TI  - Acrylonitrile polymerization by Cy3PCuMe and (Bipy)2FeEt2.
AB  - Cy(3)PCuMe (1) undergoes reversible ligand redistribution at low temperature in
      solution to form the tight ion pair [Cu(PCy(3))(2)][CuMe(2)] (3). The structure
      of 3 was assigned on the basis of (i) the stoichiometry of the 1 = 3 equilibrium,
      (ii) the observation of a triplet for the PCy(3) C1 (13)C NMR resonance due to
      virtual coupling to two (31)P nuclei, and (iii) reverse synthesis of 1 by
      combining separately generated Cu(PCy(3))(2)(+) and CuMe(2)(-) ions. Complex 1
      and [Cu(PCy(3))(2)][PF(6)] (5) coordinate additional PCy(3) to form
      (Cy(3)P)(2)CuMe and [Cu(PCy(3))(3)][PF(6)], respectively, while 3 does not.
      Complex 1, free PCy(3), and (bipy)(2)FeEt(2) (2) each initiate the polymerization
      of acrylonitrile. In each case, the polyacrylonitrile contains branches that are
      characteristic of an anionic polymerization mechanism. The major initiator in
      acrylonitrile polymerization by 1 is PCy(3), which is liberated from 1. A
      transient iron hydride complex is proposed to initiate acrylonitrile
      polymerization by 2.

PMID- 14971947
TI  - Protons in supercritical water: a multistate empirical valence bond study.
AB  - Molecular dynamics simulations have been performed to analyze microscopic details
      related to aqueous solvation of excess protons along the supercritical T = 673 K
      isotherm, spanning a density interval from a typical liquid down to vapor
      environments. The simulation methodology relies on a multistate empirical valence
      bond Hamiltonian model that includes a proton translocation mechanism. Our
      results predict a gradual stabilization of the solvated Eigen cation
      [H(3)O.(H(2)O)(3)](+) at lower densities, in detriment of the symmetric Zundel
      dimer [H.(H(2)O)(2)](+). At all densities, the average solvation structure in the
      close vicinity of the hydronium is characterized by three hydrogen bond acceptor
      water molecules and presents minor changes in the solute water distances.
      Characteristic times for the proton translocation jumps have been computed using
      population relaxation time correlation functions. Compared to room temperature
      results, the rates at high densities are 4 times faster and become progressively
      slower in steamlike environments. Diffusion coefficients for the excess proton
      have also been computed. In agreement with conductometric data, our results show
      that contributions from the Grotthus mechanism to the overall proton transport
      diminish at lower densities and predict that in steamlike environments, the
      proton diffusion is almost 1 order of magnitude slower than that for pure water.
      Spectroscopic information for the solvated proton is accordant to the gradual
      prevalence of proton localization in Eigen-like structures at lower densities.

PMID- 14971948
TI  - Binding of an acetic acid ligand to adenosine: a low-temperature NMR study.
AB  - Binding of an acetic acid (HAc) ligand to adenosine (A) was studied by (1)H NMR
      spectroscopic techniques. Using a low-melting deuterated Freon mixture as
      solvent, liquid-state measurements could be performed in the slow exchange regime
      and allowed a detailed characterization of the formed associates. Thus, at 128 K,
      trimolecular complexes A.HAc(2) and A(2).HAc with both Watson-Crick and Hoogsteen
      sites of the central adenine base occupied coexist in various amounts depending
      on the adenosine:acetic acid molar ratio. Whereas the carboxylic acid OH proton
      is located closer to the acid for all hydrogen bonds formed, a more deshielded
      proton at the Watson-Crick site is evidence for a stronger hydrogen bond as
      compared to the Hoogsteen interaction. For the binding of acetic acid to an
      adenosine-thymidine base pair in either a Watson-Crick or a Hoogsteen
      configuration, hydrogen bonds to the available adenine binding site are
      strengthened as compared to the corresponding hydrogen bonds in the A.HAc(2)
      complex.

PMID- 14971949
TI  - Diffusion NMR spectroscopy for the characterization of the size and interactions
      of colloidal matter: the case of vesicles and nanoparticles.
AB  - We report the application of the pulse gradient spin-echo (PGSE) NMR technique
      (PGSE NMR) to the analysis of large colloidal materials, specifically vesicles
      formed from macromolecular amphiphiles and nanoparticles. Measurements of size
      and size distribution were demonstrated to be comparable to those obtained
      through dynamic light scattering or hydrodynamic chromatography. In comparison to
      these more common analytical methods, the use of PGSE NMR is particularly
      advantageous in that, as a spectroscopic technique, it adds chemical selectivity
      to the study of physical dimensions. In this way, chemically different species
      contemporarily present in a sample may be individually studied. In addition, we
      demonstrate the use of PGSE NMR to probe the existence of equilibria between
      macroamphiphiles present in solution and those present in vesicles or on the
      surface of nanoparticles. This feature in particular opens exciting possibilities
      for the characterization of the phase behavior and of the surface adsorption
      phenomena of colloids.

PMID- 14971950
TI  - Definitive spectroscopic determination of zero-field splitting in high-spin
      cobalt(II).
AB  - A high-spin Co(II) complex (3d(7), S = 3/2), Co(PPh(3))(2)Cl(2) (Ph = phenyl),
      has been investigated in the solid state by both high-frequency and -field
      electron paramagnetic resonance (HFEPR) and by variable-temperature, variable
      field magnetic circular dichroism (VTVH-MCD). In HFEPR spectroscopy, the
      combination of variable sub-THz frequencies generated by backward wave
      oscillators (150-700 GHz, corresponding to energy 5-23 cm(-1)) and high magnetic
      fields (0-25 T) constitutes a novel experimental technique allowing accurate
      determination of a complete set of spin Hamiltonian parameters for this complex:
      D = -14.76(2) cm(-1), E = 1.141(8) cm(-1), g(x) = 2.166(4), g(y) = 2.170(4), g(z)
      = 2.240(5). Independent VTVH-MCD studies on multiple absorption bands of the
      complex yield D = -14(3) cm(-1), E = 0.96(20) cm(-1) (absolute value of E/D =
      0.08(2)), g(x) = 2.15(5), g(y) = 2.16(4), and g(z) = 2.17(3). This very good
      agreement between HFEPR and MCD indicates that there is no inherent discrepancy
      between these two quite different experimental techniques. Thus, depending on the
      nature of the sample, either can be reliably used to determine zero-field
      splitting parameters in high-spin Co(II), with the HFEPR being more accurate but
      VTVH-MCD being more sensitive.

PMID- 14971951
TI  - Single-molecule magnets: a large Mn30 molecular nanomagnet exhibiting quantum
      tunneling of magnetization.
AB  - The largest single-molecule magnet (SMM) to date has been prepared and studied.
      Recrystallization of known [Mn(12)O(12)(O(2)CCH(2)Bu(t))(16)(H(2)O)(4)] (1;
      8Mn(III), 4Mn(IV)) from CH(2)Cl(2)/MeNO(2) causes its conversion to
      [Mn(30)O(24)(OH)(8)(O(2)CCH(2)Bu(t))(32)(H(2)O)(2)(MeNO(2))(4)] (2; 3Mn(II),
      26Mn(III), Mn(IV)). The structure of 2 consists of a central, near-linear
      [Mn(4)O(6)] backbone, to either side of which are attached two
      [Mn(13)O(9)(OH)(4)] units. Peripheral ligation around the resulting
      [Mn(30)O(24)(OH)(8)] core is by 32 Bu(t)CH(2)CO(2)(-), 2 H(2)O, and 4 MeNO(2)
      groups. The molecule has crystallographically imposed C(2) symmetry. Variable
      temperature and -field magnetization (M) data were collected in the 1.8-4.0 K and
      0.1-0.4 T ranges and fit by matrix diagonalization assuming only the ground state
      is occupied at these temperatures. The fit parameters were S = 5, D = -0.51 cm(
      1) = -0.73 K, and g = 2.00, where D is the axial zero-field splitting parameter.
      AC susceptibility measurements in the 1.8-7.0 K range in a zero DC field and a
      3.5 G AC field oscillating at frequencies in the 50-997 Hz range revealed a
      frequency-dependent out-of-phase (chi(M)'') signal below 3 K, indicating 2 to be
      a single-molecule magnet (SMM), the largest yet obtained. Magnetization versus DC
      field sweeps show hysteresis loops but no clear steps characteristic of quantum
      tunneling of magnetization (QTM). However, magnetization decay data below 1 K
      were collected and used to construct an Arrhenius plot that revealed temperature
      independent relaxation below 0.3 K. The fit of the thermally activated region
      above approximately 0.5 K gave U(eff)/k = 15 K, where U(eff) is the effective
      relaxation barrier. Resonant QTM was confirmed from the appearance of a "quantum
      hole" when the recent quantum hole digging method was employed. The combined
      results demonstrate that SMMs can be prepared that are significantly larger than
      any known to date and that this new, large Mn(30) complex still demonstrates
      quantum behavior.

PMID- 14971952
TI  - Long range 1,4 and 1,6-interstrand cross-links formed by a trinuclear platinum
      complex. Minor groove preassociation affects kinetics and mechanism of cross-link
      formation as well as adduct structure.
AB  - Reported here is a comparison of the kinetics of the stepwise formation of 1,4-
      and 1,6-GG interstrand cross-links by the trinuclear platinum anticancer compound
      (15)N-[[trans-PtCl(NH(3))(2)](2)[mu-trans
      Pt(NH(3))(2)(H(2)N(CH(2))(6)NH(2))(2)]](4+), (1,0,1/t,t,t (1) or BBR3464). The
      reactions of (15)N-1 with the self-complementary 12-mer duplexes 5'
      [d(ATATGTACATAT)(2)] (I) and 5'-[d(TATGTATACATA)(2)] (II) have been studied at
      298 K, pH 5.3 by [(1)H,(15)N] HSQC 2D NMR spectroscopy. The kinetic profiles for
      the two reactions are similar. For both sequences initial electrostatic
      interactions with the DNA are observed for 1 and the monoaqua monochloro species
      (2) and changes in the chemical shifts of certain DNA (1)H resonances are
      consistent with binding of the central charged [PtN(4)] linker unit in the minor
      groove. The pseudo first-order rate constants for the aquation of 1 to 2 in the
      presence of duplex I (3.94 +/- 0.03 x 10(-5) s(-1)), or II(4.17 +/- 0.03 x 10(-5)
      s(-1)) are ca. 40% of the value obtained for aquation of 1 under similar
      conditions in the absence of DNA. Monofunctional binding to the guanine N7 of the
      duplex occurs with rate constants of 0.25 +/- 0.02 M(-1) s(-1) (I) and 0.34 +/-
      0.02 M(-1) s(-1) (II), respectively. Closure to form the 1,4- or 1,6-interstrand
      cross-links (5) was treated as direct from 3 with similar rate constants of 4.21
      +/- 0.06 x 10(-5) s(-1) (I) and 4.32 +/- 0.04 x 10(-5) s(-1) (II), respectively.
      Whereas there is only one predominant conformer of the 1,6 cross-link, evidence
      from both the (1)H and [(1)H,(15)N] NMR spectra show formation of two distinct
      conformers of the 1,4 cross-link, which are not interconvertible. Closure to give
      the major conformer occurs 2.5-fold faster than for the minor conformer. The
      differences are attributed to the initial preassociation of the central linker of
      1 in the minor groove and subsequently during formation of both the
      monofunctional and bifunctional adducts. For duplex I, molecular models indicate
      two distinct pathways for the terminal [PtN(3)Cl] groups to approach and bind the
      guanine N7 in the major groove with the central linker anchored in the minor
      groove. To achieve platination of the guanine residues in duplex II the central
      linker remains in the minor groove but 1 must diffuse off the DNA for covalent
      binding to occur. Clear evidence for movement of the linker group is seen at the
      monofunctional binding step from changes of chemical shifts of certain CH(2)
      linker protons as well as the Pt-NH(3) and Pt-NH(2) groups. Consideration of the
      (1)H and (15)N shifts of peaks in the Pt-NH(2) region show that for both the 1,4
      and 1,6 interstrand cross-links there is a gradual and irreversible
      transformation from an initially formed conformer(s) to product conformer(s) in
      which the amine protons of the two bound [PtN(3)] groups exist in a number of
      different environments. The behavior is similar to that observed for the 1,4
      interstrand cross-link of the dinuclear 1,1/t,t compound. The potential
      significance of preassociation in determining kinetics of formation and structure
      of the adducts is discussed. The conformational flexibility of the cross-links is
      discussed in relation to their biological processing, especially protein
      recognition and repair, which are critical determinants of the cytotoxicity of
      these unique DNA-binding agents.

PMID- 14971953
TI  - Photoswitchable flexible and shape-persistent dendrimers: comparison of the
      interplay between a photochromic azobenzene core and dendrimer structure.
AB  - Two analogous classes of dendrimers with a single azobenzene moiety at the core
      have been prepared. Flexible benzyl aryl ether dendrimers 1a-e were obtained in
      good yields by direct alkylation of diphenolic azobenzene 3 with benzyl aryl
      ether dendrons [G-n]-Br (n = 0-4). In rigid dendrimers 2a-e, the azobenzene
      configurational switch was linked to phenylacetylene dendrons through acetylenic
      linkages to maintain the shape-persistent nature of these dendrimers. A
      comparison of these two different classes of dendrimers with azobenzene cores
      reveals a difference in the properties of the photochromic moiety upon dendritic
      incorporation as well as a significant difference in the photomodulation of
      dendrimer properties. The E --> Z photoisomerization quantum yield decreased
      markedly with increasing generation for dendrimers 1a-e but only slightly for
      dendrimers 2a-e. However, increasing generation did not significantly alter
      thermal isomerization kinetics or activation barriers. The hydrodynamic volumes
      of azobenzene-containing dendrimers 2b-e were significantly modulated when the
      azobenzene unit is subjected to irradiation, while those of dendrimers 1b-e were
      only slightly affected.

PMID- 14971954
TI  - Nature of one-dimensional short hydrogen bonding: bond distances, bond energies,
      and solvent effects.
AB  - On the basis of recently synthesized calix[4]hydroquinone (CHQ) nanotubes which
      were self-assembled with infinitely long one-dimensional (1-D) short hydrogen
      bonds (SHB), we have investigated the nature of 1-D SHB using first-principles
      calculations for all the systems including the solvent water. The H-bonds relay
      (i.e., contiguous H-bonds) effect in CHQs shortens the H...O bond distances
      significantly (by more than 0.2 A) and increases the bond dissociation energy to
      a large extent (by more than approximately 4 kcal/mol) due to the highly enhanced
      polarization effect along the H-bond relay chain. The H-bonds relay effect shows
      a large increase in the chemical shift associated with the SHB. The average
      binding energies for the infinite 1-D H-bond arrays of dioles and dions increase
      by approximately 4 and approximately 9 kcal/mol per H-bond, respectively. The
      solvent effect (due to nonbridging water molecules) has been studied by
      explicitly adding water molecules in the CHQ tube crystals. This effect is found
      to be small with slight weakening of the SHB strength; the H...O bond distance
      increases only by 0.02 A, and the average binding energy decreases by
      approximately 1 kcal/mol per H-bond. All these results based on the first
      principles calculations are the first detailed analysis of energy gain by SHB and
      energy loss by solvent effect, based on a partitioning scheme of the interaction
      energy components. These reliable results elucidate not only the self-assembly
      phenomena based on the H-bond relay but also the solvent effect on the SHB
      strength.

PMID- 14971955
TI  - A concise synthesis of the octalactins.
AB  - The total synthesis of octalactins A and B has been achieved in 15 steps (longest
      linear sequence) and 10% overall yield from commercially available materials. Key
      steps include the Paterson-Aldol reaction for the rapid assembly of the carbonate
      46, methylenation of 46 and subsequent Claisen rearrangement of the corresponding
      alkenyl-substituted cyclic ketene acetal to provide the core unsaturated medium
      ring lactone 47, and the use of enzyme-mediated acetate deprotection in the
      presence of a medium-ring lactone.

PMID- 14971956
TI  - Molecular simulations suggest protein salt bridges are uniquely suited to life at
      high temperatures.
AB  - A series of explicit solvent molecular dynamics simulations has been performed to
      investigate the temperature dependence of salt bridge interactions between two
      freely diffusing amino acids. The simulations, performed at 25, 50, 75, and 100
      degrees C, allow a large number of distinct association and dissociation events
      to be directly observed, without the imposition of additional forces to drive
      association. Analysis of contact frequencies for atom pairs demonstrates that the
      number of salt bridge contacts between the two molecules is unaffected by
      temperature, whereas the numbers of hydrophobic and polar contacts are greatly
      diminished. A second, independent set of simulations-using rigid, prototypical
      molecule types-allows the differing temperature dependences of hydrophobic,
      polar, and salt bridge interactions to be unambiguously examined. In the
      prototype molecule simulations, the salt bridge interaction is found to
      substantially increase in stability at 100 degrees C relative to 25 degrees C.
      This difference in behavior between flexible amino acids and rigid prototype
      molecules is perhaps a direct manifestation of the effects of conformational
      entropy on association thermodynamics. Overall, the results demonstrate that salt
      bridge interactions are extremely resilient to temperature increases and, as
      such, are uniquely suited to promoting protein stability at high temperatures.

PMID- 14971957
TI  - Dynamic nature of the intramolecular electronic coupling mediated by a solvent
      molecule: a computational study.
AB  - We present a combined Molecular Dynamics/Quantum Chemical study of the solvent
      mediated electronic coupling between an electron donor and acceptor in a C-clamp
      molecule. We characterize the coupling fluctuations due to the solvent motion for
      different solvents (acetonitrile, benzene, 1,3-diisopropyl-benzene) for the
      charge separation and the charge recombination processes. The time scale for
      solvent-induced coupling fluctuation is approximately 0.1 ps. The effect of these
      fluctuations on the observed rate is discussed using a recently developed
      theoretical model. We show that, while the microscopic charge transfer process is
      very complicated and its computational modeling very subtle, the macroscopic
      phenomenology can be captured by the standard models. Analyzing the contribution
      to the coupling given by different solvent orbitals, we find that many solvent
      orbitals mediate the electron transfer and that paths through different solvent
      orbitals can interfere constructively or destructively. A relatively small subset
      of substrate-solvent configurations dominate contributions to solvent-mediated
      coupling. This subset of configurations is related to the electronic structure of
      the C-clamp molecule.

PMID- 14971958
TI  - Dynamics of proton transfer in bacteriorhodopsin.
AB  - Proton transfer in bacteriorhodopsin from the cytoplasm to the extracellular side
      is initiated from protonated asp96 in the cytoplasmic region toward the
      deprotonated Schiff base. This occurs in the transition from the photocycle late
      M state to the N state. To investigate this proton-transfer process, a quantum
      mechanics/molecular mechanics (QM/MM) model is constructed from the
      bacteriorhodopsin E204Q mutant crystal structure. Three residues, asp96, asp85,
      and thr89, as well as most of the retinal chromophore and the Schiff base link of
      lys216 are treated quantum mechanically and connected to the remaining classical
      protein through linker atom hydrogens. Structural transformation in the M state
      results in the formation of a water channel between the Schiff base and asp96.
      Since a part of this channel is lined with hydrophobic residues, there has been a
      question on the mechanism of proton transfer in a hydrophobic channel. Ab initio
      dynamics using the CHARMM/GAMESS methodology is used to simulate the transfer of
      the proton through a partially hydrophobic channel. Once sufficient water
      molecules are added to the channel to allow the formation of a single chain of
      waters from asp96 to the Schiff base, the transfer occurs as a fast (less than a
      picosecond) concerted event irrespective of the protonation state of asp85.
      Dynamic transfer of the proton from asp96 to the nearest water initiates the
      organization of a strongly bonded water chain conducive to the transfer of the
      proton to the Schiff base nitrogen.

PMID- 14971959
TI  - Separation of anisotropic and steric substituent effects-nuclear chemical
      shielding analysis of H-4 and C-4 in phenanthrene and 11-ethynylphenanthrene.
AB  - The anisotropic effect of a proximally introduced ethynyl group on the chemical
      shifts of H-4 and C-4 of the phenanthrene skeleton was calculated using GIAO
      HF/NICS methodology. The anisotropic effect, long considered to be the source of
      the considerable downfield shift of H-4 in 11-ethynylphenanthrene in comparison
      to the chemical shift value of the corresponding proton in phenanthrene, was
      determined to be only negligible in magnitude on the basis of these calculations.
      Partitioning of the natural chemical shieldings of H-4 and C-4 by the NCS-NBO
      method into various contributions from the C-C and C-H bonds present in each
      molecule revealed that steric compression was able to account for the large
      downfield shifts of both H-4 and C-4 in 11-ethynylphenanthrene relative to
      phenanthrene. Thus, the substituent effect is almost totally permeated by this
      latter interaction and not by the aforementioned process, which was previously
      presumed to be the sole underlying cause.

PMID- 14971960
TI  - Electronic structure of the cysteine thiyl radical: a DFT and correlated ab
      initio study.
AB  - The electronic structure and the unusual EPR parameters of sulfur-centered alkyl
      thiyl radical from cysteine are investigated by density functional theory (DFT)
      and correlated ab initio calculations. Three geometry-optimized, staggered
      conformations of the radical are found that lie within 630 cm(-1) in energy. The
      EPR g-values are sensitive to the energy difference between the nearly-degenerate
      singly occupied orbital and one of the lone-pair orbitals (excitation energies of
      1732, 1083, and 3429 cm(-1) from Multireference Configuration Interaction
      calculations for the structures corresponding to the three minima), both of which
      are almost pure sulfur 3p orbitals. Because of the near degeneracy, the second
      order correction to the g tensor, which is widely used to analyze g-values of
      paramagnetic systems, is insufficient to obtain accurate g-values of the cysteine
      thiyl radical. Instead, an expression for the g tensor must be used in which
      third order corrections are taken into account. The near-degeneracy can be
      affected to roughly equal extents by changes in the structure of the radical and
      by hydrogen bonds to the sulfur. The magnitude of the hyperfine coupling
      constants for the beta protons of the cysteine thiyl radical is found to depend
      on the structure of the radical. On the basis of a detailed comparison between
      experimental and calculated g-values and hyperfine coupling constants an attempt
      is made to identify the structure of thiyl radicals and the number of hydrogen
      bonds to the sulfur.

PMID- 14971961
TI  - NMR R1 rho rotating-frame relaxation with weak radio frequency fields.
AB  - NMR spin relaxation in the rotating frame (R(1 rho)) is one of few methods
      available to characterize chemical exchange kinetic processes occurring on micros
      ms time scales. R(1 rho) measurements for heteronuclei in biological
      macromolecules generally require decoupling of (1)H scalar coupling interactions
      and suppression of cross-relaxation processes. Korzhnev and co-workers
      demonstrated that applying conventional (1)H decoupling schemes while the
      heteronuclei are spin-locked by a radio frequency (rf) field results in imperfect
      decoupling [Korzhnev, Skrynnikov, Millet, Torchia, Kay. J. Am. Chem. Soc. 2002,
      124, 10743-10753]. Experimental NMR pulse sequences were presented that provide
      accurate measurements of R(1 rho) rate constants for radio frequency field
      strengths > 1000 Hz. This paper presents new two-dimensional NMR experiments that
      allow the use of weak rf fields, between 150 and 1000 Hz, in R(1 rho)
      experiments. Fourier decomposition and average Hamiltonian theory are employed to
      analyze the spin-lock sequence and provide a guide for the development of
      improved experiments. The new pulse sequences are validated using ubiquitin and
      basic pancreatic trypsin inhibitor (BPTI). The use of weak spin-lock fields in
      R(1 rho) experiments allows the study of the chemical exchange process on a wider
      range of time scales, bridging the gap that currently exists between Carr-Purcell
      Meiboom-Gill and conventional R(1 rho) experiments. The new experiments also
      extend the capability of the R(1 rho) technique to study exchange processes
      outside the fast exchange limit.

PMID- 14971963
TI  - Impact of a walking program in people with down syndrome.
AB  - The purpose of this study was to evaluate the efficacy of a pain-free treadmill
      walking program in intellectually disabled (ID) adults with arterial occlusive
      disease. Fourteen participants with mild ID participated in the walking program.
      Six patients showed stable intermittent claudication. A control (nontreadmill, n
      = 12) group consisted of 4 individuals with intermittent claudication.
      Noninvasive determinations of lower-limb hemodynamics included
      photoplethysmography and ankle-brachial pressure. Pain levels were measured
      according to a pain pathophysiology index. The treadmill program consisted of
      individually prescribed low-endurance walking at a 0% incline done at a
      comfortable speed 3 times per week. All participants completed the 15-week
      walking program and showed significant improvements (p < 0.05) in walking speed,
      distance, and duration. Pain levels were reduced in individuals suffering from
      intermittent claudication. Blood hemodynamic parameters also showed significant
      improvements. In conclusion, low-intensity treadmill walking significantly
      improved the functional capacities of adult individuals with mild ID with
      vascular occlusion and reduced pain levels.

PMID- 14971964
TI  - Effects of liquid carbohydrate ingestion on markers of anabolism following high
      intensity resistance exercise.
AB  - We examined the effects of liquid carbohydrate (CHO) supplementation on markers
      of anabolism following high-intensity resistance exercise. Nine resistance
      trained men consumed either CHO or placebo (PLC) 10 minutes before and
      immediately following 2 resistance exercise sessions. Cortisol (CORT), insulin
      (INS), ammonia (AMM), and glucose (GLU) were measured before, immediately after,
      and 1.5 and 4 hours after exercise. Urinary nitrogen (NH(+3)) was measured 24
      hours before and after exercise. There was a significant difference in INS levels
      immediately after exercise and 1.5 hours after exercise. No significant
      differences were observed for CORT, AMM, GLU, or NH(+3)between treatments.
      Significant within-group differences were found for the PLC group: CORT before
      compared with immediately after exercise; INS before compared with immediately
      after exercise and before compared with 1.5 hours after exercise; and AMM before
      compared with immediately after exercise and before compared with 1.5 hours after
      exercise. Significant within-group differences were found for the CHO group: CORT
      immediately after compared with 1.5 hours after exercise and immediately after
      compared with 4 hours after exercise; INS before compared with 1.5 hours after
      exercise; and AMM before compared with immediately after exercise. Liquid CHO
      ingestion leads to a more favorable anabolic environment immediately following a
      resistance exercise bout; however, our indirect measures of protein degradation
      were not altered by CHO ingestion.

PMID- 14971965
TI  - Effect of two and five days of creatine loading on anaerobic working capacity in
      women.
AB  - The purpose of this study was to determine the effects of 2 and 5 days of Cr
      loading on anaerobic working capacity (AWC) using the critical power (CP) test in
      women. Ten physically active women randomly received 2 treatments separated by a
      5 week washout period: (A) 18 g dextrose as placebo (PL) or (B) 5.0 g Cr + 18 g
      dextrose taken 4 times per day for 5 days. Following a familiarization trial,
      each subject completed the CP test at baseline and following 2 and 5 days of
      supplementation. The PL resulted in no significant changes in AWC following
      supplementation; however, Cr increased AWC by 22.1% after 5 days of loading (p <
      0.05). There was a significant main effect for body weight (BW), however, there
      was no significant increase in BW due to Cr supplementation. These results
      suggest that Cr supplementation is effective for increasing AWC in women
      following 5 days of loading without an associated increase in BW.

PMID- 14971966
TI  - Effects of repeated creatine supplementation on muscle, plasma, and urine
      creatine levels.
AB  - The purpose of this case study was to examine the effects of repeated creatine
      administration on muscle phosphocreatine, plasma creatine, and urine creatine.
      One male subject (age, 32 years; body mass, 78.4 kg; height, 160 cm; resistance
      training experience, 15 years) ingested creatine (20 g.d(-1) for 5 days) during 2
      bouts separated by a 30-day washout period. Muscle phosphocreatine was measured
      before and after supplementation. On day 1 of supplementation, blood samples were
      taken immediately before and hourly for 5 hours following ingestion of 5 g of
      creatine, and a pharmacokinetic analysis of plasma creatine was conducted. Twenty
      four-hour urine collections were conducted before and for 5 days during
      supplementation. Muscle phosphocreatine increased 45% following the first
      supplementation bout, decreased 22% during the 30-day washout period, and
      increased 25% following the second bout. There were no meaningful differences in
      plasma creatine pharmacokinetic parameters between bouts 1 and 2. Total urine
      creatine losses during supplementation were 63.2 and 63.4 g during bouts 1 and 2,
      respectively. The major findings were that (a) a 30-day washout period is
      insufficient time for muscle phosphocreatine to return to baseline following
      creatine supplementation but is sufficient time for plasma and urine creatine
      levels to return to presupplementation values; (b) postsupplementation muscle
      phosphocreatine levels were similar following bouts 1 and 2 despite 23% higher
      presupplementation muscle phosphocreatine before bout 2; and (c) the increased
      muscle phosphocreatine that persisted throughout the 30-day washout period
      corresponded with maintenance of increased body mass (+2.0 kg). Athletes should
      be aware that the washout period for muscle creatine to return to baseline levels
      may be longer than 30 days in some individuals, and this may be accompanied by a
      persistent increase in body mass.

PMID- 14971967
TI  - Effects of deep heat as a preventative mechanism on delayed onset muscle
      soreness.
AB  - The effects of increased muscle temperature via continuous ultrasound prior to a
      maximal bout of eccentric exercise were investigated on the symptoms of delayed
      onset muscle soreness (DOMS) of the elbow flexors. Perceived muscle soreness,
      upper arm circumferences, range of motion (ROM), and isometric and isokinetic
      strength were measured over 7 days on 14 college-aged men (n = 6) and women (n =
      8). Ten minutes of continuous ultrasound (ULT) or sham-ultrasound (CON) were
      administered. Muscle temperature was measured in the biceps brachii of both arms.
      Muscle temperature increased by 1.79 degrees +/- 0.49 degrees C (mean +/- SD) in
      the experimental arm of the ULT group. Muscle soreness was induced by a single
      bout of 50 maximal eccentric contractions. The ULT group did not differ
      significantly (p < 0.05) from the CON group with respect to perceived muscle
      soreness, upper arm circumference, ROM, and isometric and isokinetic strength. In
      conclusion, increased muscle temperature failed to provide significant
      prophylactic effects on the symptoms of DOMS.

PMID- 14971968
TI  - Morning vs. evening maximal cycle power and technical swimming ability.
AB  - The aim of this study was to observe diurnal influences on maximal power and
      technical swimming ability at three different times (8 AM, 1 PM, and 6 PM). Prior
      to each test, tympanic temperature was taken. Maximal power was analyzed by cycle
      tests. Stroke length, stroke rate, hand pattern, and swimming velocity were
      recorded between the 20th and the 28th m of the 50-m freestyle. Temperature
      varied +/-0.4 degrees C between morning and evening. Concomitantly, maximal power
      (+7%) and technical ability (+3% in stroke length, +5% in stroke rate and changes
      in underwater hand coordinates) were greater in the evening. The present study
      confirms and specifies diurnal influences on all-out performances with regard to
      both maximal power and technical ability. Thus, when swimmers are called upon to
      perform at a high level in the morning, they should warm up extensively in order
      to "swamp" the diurnal effects of the morning.

PMID- 14971969
TI  - Isolated vs. complex exercise in strengthening the rotator cuff muscle group.
AB  - The purpose of this study was to compare 2 different training modes in improving
      shoulder cuff muscular performance. Thirty-nine participants were randomly
      assigned into 3 groups: the isolated group exercised using 2-kg dumbbells; the
      complex group used a protocol with complex exercises; and the control group had
      no training. All participants trained for 6 weeks (3 times per week) and were
      evaluated isokinetically before (pretest) and after the training period
      (posttest). Results showed that the complex group significantly improved their
      muscular performance, but the isolated group did not, indicating that isolated
      exercises are only effective when the training goal is to strengthen the weaker
      muscle group, but they must be replaced by more complex and closed-kinetic
      exercises in order to obtain considerable improvement of the rotator cuff
      strength. The authors propose that a strengthening program should start with
      isolated movements for better stimulation of the weaker muscles and continue with
      complex exercise for more impressive strengthening.

PMID- 14971970
TI  - Can laboratory-based tennis profiles predict field tests of tennis performance?
AB  - The present study examined the impact of physical characteristics of adolescent
      competitive tennis players (13-18 years) on field tests of tennis performance.
      Results (n = 33) showed that boys were taller (p = 0.001), possessed greater
      wingspan (p = 0.030), had greater maximum oxygen consumption (p = 0.001), and
      performed better on isokinetic strength measurements. Multiple regression
      analyses controlling for age and sex showed that height (p = 0.025), maximum
      minute ventilation (p = 0.005), and isokinetic strength measurements
      significantly and positively affected ball velocity. Knee extension average power
      was the only variable to positively and significantly affect ball placement (p =
      0.040); however, several isokinetic strength measurements negatively affected
      ball placement. For the nondominant side, down-the-line strokes showed reduced
      accuracy (p = 0.001) and ball velocity (p = 0.001) compared with cross-court
      strokes. Given our results, resistance training may be beneficial for the
      performance of on-court tennis play.

PMID- 14971971
TI  - Comparison of Olympic vs. traditional power lifting training programs in football
      players.
AB  - Twenty members of an National Collegiate Athletic Association Division III
      collegiate football team were assigned to either an Olympic lifting (OL) group or
      power lifting (PL) group. Each group was matched by position and trained 4
      days.wk(-1) for 15 weeks. Testing consisted of field tests to evaluate strength
      (1RM squat and bench press), 40-yard sprint, agility, vertical jump height (VJ),
      and vertical jump power (VJP). No significant pre- to posttraining differences
      were observed in 1RM bench press, 40-yard sprint, agility, VJ or in VJP in either
      group. Significant improvements were seen in 1RM squat in both the OL and PL
      groups. After log10-transformation, OL were observed to have a significantly
      greater improvement in Delta VJ than PL. Despite an 18% greater improvement in
      1RM squat (p > 0.05), and a twofold greater improvement (p > 0.05) in 40-yard
      sprint time by OL, no further significant group differences were seen. Results
      suggest that OL can provide a significant advantage over PL in vertical jump
      performance changes.

PMID- 14971972
TI  - Changes in exercise performance and hormonal concentrations over a big ten soccer
      season in starters and nonstarters.
AB  - As a consequence of the physiological demands experienced during a competitive
      soccer season, the antagonistic relationship between anabolic and catabolic
      processes can affect performance. Twenty-five male collegiate soccer players were
      studied throughout a season (11 weeks) to investigate the effects of long-term
      training and competition. Subjects were grouped as starters (S; n = 11) and
      nonstarters (NS; n = 14). Measures of physical performance, body composition, and
      hormonal concentrations (testosterone [T] and cortisol [C]) were assessed
      preseason (T1) and 5 times throughout the season (T2-T6). Starters and NS
      participated in 83.06% and 16.95% of total game time, respectively. Nonstarters
      had a significant increase (+1.6%) in body fat at T6 compared to T1. Isokinetic
      strength of the knee extensors (1.05 rad.sec(-1)) significantly decreased in both
      S (-12%) and NS (-10%; p < or = 0.05) at T6. Significant decrements in sprint
      speed (+4.3%) and vertical jump (-13.8%) were found at T5 in S only. Though
      within normal ranges (10.4-41.6 nmol.L(-1)), concentrations of T at T1 were low
      for both groups, but increased significantly by T6. Concentrations of C were
      elevated in both groups, with concentrations at the high end of the normal range
      (normal range 138-635 nmol.L(-1)) at T1 and T4 in NS and T4 in S, with both
      groups remaining elevated at T6. Data indicate that players entering the season
      with low circulating concentrations of T and elevated levels of C can experience
      reductions in performance during a season, with performance decrements
      exacerbated in starters over nonstarters. Soccer players should therefore have a
      planned program of conditioning that does not result in an acute overtraining
      phenomenon prior to preseason (e.g., young players trying to get in shape quickly
      in the 6 to 8 weeks in the summer prior to reporting for preseason camp). The
      detrimental effects of inappropriate training do not appear to be unloaded during
      the season and catabolic activities can predominate.

PMID- 14971973
TI  - Physical characteristics that predict functional performance in Division I
      college football players.
AB  - Strength and conditioning professionals who work with collegiate football players
      focus much of their time and effort on developing programs to enhance athletic
      performance. Although there has been much speculation, there is little scientific
      evidence to suggest which combination of physical characteristics best predicts
      athletic performance in this population. The purpose of this investigation was to
      examine the relationship among 6 physical characteristics and 3 functional
      measures in college football players. Data were gathered on 46 NCAA Division I
      college football players. The 3 response variables were 36.6-m sprint, 18.3-m
      shuttle run, and vertical jump. The 6 regressor variables were height, weight,
      percentage of body fat, hamstring length, bench press, and hang clean. A stepwise
      multiple regression analysis was performed to screen for variables that predict
      physical performance. Regression analysis revealed clear prediction models for
      the 36.6-m sprint and 18.3-m shuttle run. The results of this investigation will
      help strength and conditioning specialists better understand the variables that
      predict athletic performance in Division I college football players.

PMID- 14971974
TI  - Perceived importance of weight training to selected NCAA Division III men and
      women student-athletes.
AB  - The purpose of this study was to examine differences in perception of the
      importance of weight training as a part of general and sport-specific training
      for selected collegiate men and women student-athletes. Subjects included 139 men
      and 165 women varsity National Collegiate Athletic Association Division III
      student-athletes who participated in the following sports: baseball, basketball,
      field hockey, football, lacrosse, soccer, softball, swimming, tennis, track &
      field, or volleyball. Men student-athletes were significantly more likely to
      consider weight training essential to their general and sport-specific training
      than women student-athletes, as measured by the Training Information Survey.
      Additionally, men student-athletes were found to be significantly more
      competitive and win-oriented than women student-athletes (p < 0.001) as measured
      by the Sport Orientation Questionnaire, which is consistent with previous
      research. Results also showed that only highly goal-oriented student-athletes
      perceived weight training as: (a) important to both men and women and (b) having
      both feminine and masculine traits. It was concluded that significant gender
      differences exist in the perceived importance of weight training and that the
      constructs of competitiveness, win and goal orientation, may influence a student
      athlete's perception of the importance of weight training. Coaches of both men
      and women student-athletes must teach that weight training is important for
      female and male student-athletes.

PMID- 14971975
TI  - Longitudinal tracking of muscular power changes of NCAA Division I collegiate
      women gymnasts.
AB  - Gymnastics relies upon power as a critical component of sports-specific fitness.
      The purpose of this study was to monitor long-term training adaptations in the
      power of National Collegiate Athletics Association Division I women gymnasts.
      Twenty members of a women's gymnastic team (aged 18-22) were tracked over 3 years
      with the first year a baseline year of testing. Whole body power for the counter
      movement (CMJ) and squat (SJ) vertical jump was obtained via force plate analyses
      at 2 assessment time points during each year (February and November). Results
      showed significant (p < or = 0.05) and continued increases in peak power output
      in the CMJ and SJ at each biannual assessment. Improvements of 46% (+1010 W) for
      the CMJ and 43% (+900 W) for the SJ were observed at the end of the tracking
      period. Peak power for the CMJ and SJ were recorded at 3210 W (+/-350 W) and 3000
      W (+/-152 W), respectively. Associated improvements in the time to peak power of
      36% (-0.239 second) and 38% (-0.151 second) were also found for the CMJ and SJ.
      There were no significant changes in body mass or total skinfold thickness,
      however, a shift toward improved fat free mass (i.e., lean muscle mass) was
      apparent. These data underscore the importance that specificity, and more
      importantly power development, should play in the conditioning of collegiate
      women gymnasts' training programs.

PMID- 14971976
TI  - Validity of a 5-meter multiple shuttle run test for assessing fitness of women
      field hockey players.
AB  - The aim of this study was to establish validity of a 5-m multiple shuttle test (5
      m MST) using indirect (criterion and construct) and direct measures of
      performance. For criterion validity, comparisons were made between data from
      established fitness tests and a 5-m MST. Construct validity was determined by
      comparing results from a 5-m MST with subjects of different playing abilities.
      Direct validity was determined by comparing values attained from a 5-m MST with
      data from a time-motion study of field hockey. For criterion validity, the
      strongest relationship existed between the 20-m MST (42.7 +/- 7.1 ml.kg(-1).min(
      1)) and total distance from the 5-m MST (650.9 +/- 59.2 m; r = 0.92). For
      construct validity, regional representative players covered more distance than
      club-level players (689.9 +/- 46.6 m vs. 661.1 +/- 31.0 m; p < 0.01). For direct
      validity, the highest correlation was found between total distance from the 5-m
      MST (706.0 +/- 37.5 m) and mean displacement during matches (61.0 +/- 6.0 m; r =
      0.74). It was concluded that the 5-m MST had both indirect and direct validity
      for the fitness assessment of field hockey players. The data obtained from the 5
      m MST directly relates to the physical fitness of the players during competition.

PMID- 14971977
TI  - Prediction of maximal VO2 from a submaximal StairMaster test in young women.
AB  - The StairMaster 4000 PT is a popular step ergometer which provides a submaximal
      test protocol (SM Predicted VO(2)max) for the prediction of VO(2)max (ml.kg(
      1).min(-1)). The purpose of this study was to evaluate the SM Predicted VO(2)max
      protocol by comparing it to results from a VO(2)max treadmill test in 20 young
      healthy women aged 20-25 years. Subjects were 10 step-trained (ST) women who had
      performed aerobic activities and exercised on a step ergometer for 20-30 minutes
      at least 3 times per week for the past 3 months, and 10 non-step-trained (NST)
      women who had performed aerobic activities no more than twice a week during the
      past 3 months and had no previous experience on a step ergometer. The SM
      Predicted VO(2)max protocol used 2 steady state heart rates between approximately
      115-150 b.min(-1) to estimate VO(2)max. The Bruce maximal treadmill protocol
      (Actual VO(2)max) was used to measure VO(2)max by open circuit spirometry. Each
      subject performed both tests within a 7-day period. The means and standard
      deviations for the Actual VO(2)max tests were 39.8 +/- 6.1 ml.kg(-1).min(-1) for
      the ST group, 37.6 +/- 6.3 ml.kg(-1).min(-1) for the NST group, and 38.7 +/- 6.2
      ml.kg(-1).min(-1) for the Total group (N = 20); and for the SM Predicted VO(2)max
      tests, means and standard deviations were 40.78 +/- 14.0 ml.kg(-1).min(-1), 30.9
      +/- 4.8 ml.kg(-1).min(-1) and 35.9 +/- 11.4 ml.kg(-1).min(-1). There was no
      significant difference (p > 0.05) between the means of the Actual VO(2)max and SM
      Predicted VO(2)max test for the Total group (N = 20) or the ST group (n = 10),
      but a significant difference (p < 0.05) was shown for the NST group. The
      coefficient of determination (R(2)) and standard error of estimate (SEE) for the
      SM Predicted VO(2)max and Actual VO(2)max tests were R(2) = 0.18, SEE = 5.72
      ml.kg(-1).min(-1) for the Total group; R(2) = 0.00, SEE = 6.68 ml.kg(-1).min(-1)
      for the NST group; and R(2) = 0.33, SEE = 5.32 ml.kg(-1).min(-1) for ST group. In
      conclusion, the SM Predicted VO(2)max test has acceptable accuracy for the ST
      group, but significantly underpredicted the NST group by almost 7 ml; and, as
      demonstrated by the high SEEs, it has a low level of precision for both ST and
      NST subjects.

PMID- 14971978
TI  - The effects of land vs. aquatic plyometrics on power, torque, velocity, and
      muscle soreness in women.
AB  - The purpose of this study was to compare changes in performance indicators
      (power, torque, and velocity) and muscle soreness between plyometric training on
      land and in water. Thirty-two college age women were randomly assigned to 8 weeks
      of an identical plyometric training program on land or in an aquatic setting.
      Performance indicators were assessed pretraining, midtraining, and posttraining.
      Muscle soreness (ordinal scale) and pain sensitivity (palpation) were assessed
      after a training bout (0, 48, and 96 hours) during the first week of training and
      when training intensity was increased (weeks 3 and 6). Performance indictors
      increased for both groups (pretraining < midtraining < posttraining, p < or =
      0.001). Muscle soreness was significantly greater in the land compared to the
      aquatic plyometric training group at baseline and each time training intensity
      was increased, p = 0.01. Aquatic plyometrics provided the same performance
      enhancement benefits as land plyometrics with significantly less muscle soreness.

PMID- 14971979
TI  - Prediction of indoor climbing performance in women rock climbers.
AB  - In an attempt to more clearly understand the strength characteristics of female
      rock climbers and whether those variables affect and predict climbing
      performance, 2 indoor climbing performance tests (route and bouldering) were
      compared to a series of muscular strength tests performed by moderate (n = 6),
      intermediate (n = 6), and expert (n = 6) female rock climbers. Significant
      differences (p < 0.05) were found between the expert group and the moderate and
      intermediate groups for climbing specific hand strength, as well as 1-arm lock
      off strength when expressed as a strength-to-weight ratio. Multiple correlations
      showed that these variables (r > 0.426) as well as a questionnaire of past
      climbing performance (r > 0.86) significantly correlated to the tests of indoor
      climbing performance. In conclusion, climbing-specific tests of hand strength and
      of one arm lock-off strength reliably and sensitively measured 2 significant
      variables in the performance of indoor rock climbing, and a questionnaire of past
      best performance may be an accurate tool for the prediction of indoor climbing
      performance.

PMID- 14971980
TI  - Predicting anaerobic capabilities in 11-13-year-old boys.
AB  - Anaerobic exercise is involved in many recreational and competitive sport
      activities. This study first established regression equations to predict maximal
      anaerobic power and then cross-validated these prediction equations. Using
      stepwise multiple regression analysis prediction equations for relative (watts
      per kilogram of body mass) and absolute (watts) mean and peak anaerobic power
      using the 30-second Wingate Test as the power measure were determined for 40 boys
      (age, 11-13 years). Percentage of body fat, free-fat weight, midthigh
      circumference, and 30-m dash were the independent predictive variables with the
      generated regression equations subsequently cross-validated using 20 different
      boys (age, 11-13 years). Significant correlations (Pearson r) were found for the
      cross-validation subjects between the measured power outputs and predicted power
      outputs for relative mean power (r = 0.48, p < 0.05), absolute mean power (r =
      0.77, p < 0.01), and absolute peak power (r = 0.76, p < 0.01). Using paired t
      tests, no significant mean differences (p > 0.05) were found for the same
      subjects between actual and predicted power outputs for relative mean power,
      absolute mean power, and absolute peak power. Prediction of maximal anaerobic
      power from selected anthropometric measurements and 30-m dash appears tenable in
      11-13-year-old boys and can be accomplished in a simple cost- and time-effective
      manner.

PMID- 14971981
TI  - Development of upper body power in junior cross-country skiers.
AB  - With the advent of the ski-skating technique, upper body power has increasingly
      been shown to be a major factor in cross-country skiing success. The purpose of
      this study was to evaluate 4 commonly used training methods (weight, circuit,
      rollerboard, and ski-specific training) for the development of upper body power
      (UBP) in junior cross-country skiers. Fifty-eight adolescent cross-country skiers
      (Boys: n = 29, age = 16.0 +/- 1.2 y and Girls: n = 29, age = 15.5 +/- 1.5 y) were
      assigned to one of the UBP training methods for a 10-week training program.
      Fourteen cross-country runners served as controls (boys: n = 7, age = 15.8 +/-
      1.7 y; girls: n = 7, age = 14.9 +/- 1.3 y). Skiers were evaluated pre- and post
      training for upper body strength (UBS) using a 10 repetition maximum (RM)
      rollerboard test, for UBP using a double-poling ergometer and for upper body
      endurance (UBE) with a 3-km, arms-only, rollerski endurance time trial.
      Competitive race results were collected during the winters before and after
      training as were all training data. Only the rollerboard training group improved
      significantly greater than the control group (p < 0.05) in UBP and UBS.
      Improvements in UBP, UPS, and UBE were significantly related (r = 0.545, 0.303,
      and 0.407, respectively) to improvements in competitive performance. These data
      suggest that training using a rollerboard with 5-12RM and explosive speed is more
      effective in developing UBP than other common training methods for adolescent
      cross-country skiers. The practical importance of these data was verified by the
      significant relationships between improvements in UBP, UBS, and UBE related to
      improvements in competitive race performance.

PMID- 14971982
TI  - Effect of an 8-week combined weights and plyometrics training program on golf
      drive performance.
AB  - The purpose of this study was to determine the effect of a combined weights and
      plyometrics program on golf drive performance. Eleven male golfers' full golf
      swing was analyzed for club head speed (CS) and driving distance (DD) before and
      after an 8-week training program. The control group (n = 5) continued their
      normal training, while the experimental group (n = 6) performed 2 sessions per
      week of weight training and plyometrics. Controls showed no significant (p > or =
      0.05) changes, while experimental subjects showed a significant increase (p < or
      = 0.05) in CS and DD. The changes in golf drive performance were attributed to an
      increase in muscular force and an improvement in the sequential acceleration of
      body parts contributing to a greater final velocity being applied to the ball. It
      was concluded that specific combined weights and plyometrics training can help
      increase CS and DD in club golfers.

PMID- 14971983
TI  - Normalizing expressions of strength in elite rugby league players.
AB  - Physical strength has often been expressed per kilogram of body mass. Research
      suggests that strength increases in proportion to a body mass raised to a power
      between 0.6 and 0.7 rather than the ratio held exponent of 1. The current study
      was designed to identify differences in the strength of elite-level rugby league
      players and to identify whether ratio (per kg(-1)) expressions would penalize
      heavier subjects. Fifty-four elite rugby league players were recruited to the
      study during the preseason. Subjects were classified according to their highest
      playing level. Players performed 3 maximal lifts, using a dynamometer, to
      determine leg strength. Body mass and muscle mass estimations were also recorded.
      Results showed that absolute expressions of strength revealed differences by
      playing level (p < 0.05). These differences were removed when a ratio scaling
      technique was applied (p > 0.05). Mass and muscle mass exponents of 0.62 and 0.63
      were derived and applied to the strength data. Differences in strength by playing
      level were reestablished following this adjustment (p < 0.05). These findings
      emphasize that ratio (per kg(-1)) expressions, despite being commonly used, can
      penalize heavier athletes and mask differences in performance. Coaches and sports
      scientists should reconsider using the ratio expression due to its potential for
      error when describing physical strength.

PMID- 14971984
TI  - Maximal strength and power assessment in novice weight trainers.
AB  - The purpose of this study was to investigate whether changes in maximal strength
      and power output occurred over time in the absence of strength and power training
      in novice weight trainers. It also investigated whether differences existed
      between upper- and lower-body assessments and unilateral and bilateral
      assessments. The power output and maximal strength (1 repetition maximum [1RM])
      of 10 male novice subjects were measured on 4 occasions, each assessment 7-10
      days apart. The exercises used to measure the upper- and lower-body strength and
      power outputs were the bench press and supine squat, respectively. Significant (p
      < 0.05) changes in unilateral (9.8-16.8%) and bilateral 1RM (6.8-15.0%) leg
      strength were found, the first assessment being significantly different from all
      other assessments and assessment 2 significantly different from assessment 4.
      Changes in the upper body (10-13.6%) were also observed. The only significant
      difference was between assessment 1 and the other testing occasions. No
      differences in power output were observed for both the upper and lower body
      during the study. It would seem that considerable changes in maximal strength
      occur rapidly and in the absence of any formal strength training program in
      novice weight trainers.

PMID- 14971985
TI  - Quantitative analysis of single- vs. multiple-set programs in resistance
      training.
AB  - The purpose of this study was to examine the existing research on single-set vs.
      multiple-set resistance training programs. Using the meta-analytic approach, we
      included studies that met the following criteria in our analysis: (a) at least 6
      subjects per group; (b) subject groups consisting of single-set vs. multiple-set
      resistance training programs; (c) pretest and posttest strength measures; (d)
      training programs of 6 weeks or more; (e) apparently "healthy" individuals free
      from orthopedic limitations; and (f) published studies in English-language
      journals only. Sixteen studies generated 103 effect sizes (ESs) based on a total
      of 621 subjects, ranging in age from 15-71 years. Across all designs,
      intervention strategies, and categories, the pretest to posttest ES in muscular
      strength was (chi = 1.4 +/- 1.4; 95% confidence interval, 0.41-3.8; p < 0.001).
      The results of 2 x 2 analysis of variance revealed simple main effects for age,
      training status (trained vs. untrained), and research design (p < 0.001). No
      significant main effects were found for sex, program duration, and set end point.
      Significant interactions were found for training status and program duration (6
      16 weeks vs. 17-40 weeks) and number of sets performed (single vs. multiple). The
      data indicated that trained individuals performing multiple sets generated
      significantly greater increases in strength (p < 0.001). For programs with an
      extended duration, multiple sets were superior to single sets (p < 0.05). This
      quantitative review indicates that single-set programs for an initial short
      training period in untrained individuals result in similar strength gains as
      multiple-set programs. However, as progression occurs and higher gains are
      desired, multiple-set programs are more effective.

PMID- 14971986
TI  - Training diagnosis for a load carriage task.
AB  - To explore the possibility of training diagnosis for a 3.2-km loaded march with a
      25 kg load, 50 men trained for 10 weeks using either running, marching, and
      endurance-based circuit training (Circuits), or running, marching, and resistance
      training (Resistance). The march was performed before and after training, and
      other measurements related to loaded marching were conducted before training
      only. Each group was ranked by improvement in the loaded march, and divided into
      significantly different subgroups of 'good' and 'poor' responders (improvements
      of approximately 20% vs. 10%). For Circuits, there were significant differences
      between good and poor responders to training in the pretraining ratios of shuttle
      run: isometric lift strength (p = 0.031) and shuttle run: isometric back
      extension strength (p = 0.033). Stronger subjects with lower endurance responded
      better to Circuits. Resistance tended to show the opposite effect (p < 0.2).
      These are the first objective data on which to prescribe training for load
      carriage on an individual basis.

PMID- 14971987
TI  - Verbal messages strengthen bench press efficacy.
AB  - This study examined the effects of verbal messages on bench press efficacy: the
      confidence to lift progressively heavier weights for 1 repetition. Thirty-two
      women who had not bench pressed within the previous 18 months were assigned to 1
      of 2 groups and exposed to 2 sources of efficacy information. First, subjects in
      both groups performed 10 repetitions on a fixed movement, vertical bench press
      machine and completed the bench press efficacy scale. Next, each group received 1
      of 2 possible verbal messages. Both messages included the speaker's strength
      training qualifications. In addition, one message conveyed specific performance
      feedback while the other contained more general information. Then efficacy was
      measured again. Results indicated both messages strengthened efficacy. Strength
      professionals who work one-on-one with novice women should: (a) make sure lifters
      are aware of their professional qualifications, (b) provide specific feedback,
      and (c) profess their beliefs in the lifters' abilities to perform the exercises.

PMID- 14971988
TI  - Job analysis of college Division I-A football strength and conditioning coaches.
AB  - This investigation consisted of a job analysis of 6 National Collegiate Athletic
      Association Division I-A strength and conditioning coaches (SCC). All the
      subjects in the study were primarily responsible for providing strength and
      conditioning services to their institution's football programs. The procedures
      used for the gathering of data consisted of 3 questionnaires and a semi
      structured interview. The questionnaires were followed up by the semi-structured
      interview. The purpose of this format was to use the semi-structured interview to
      delve more deeply into the issues raised by the questionnaires. The major job
      responsibilities and tasks are highlighted. These included conducting training
      session for athletes, disciplining athletes for infractions of team rules, on
      campus recruiting, and professional scout liaison to the National Football
      League. These coaches' perceptions concerning their profession, work environment,
      relationships with supervisors and co-workers, and the effect the job has on
      their spouses and other family members are also emphasized.

PMID- 14971989
TI  - Study of the key determining factors for the NCAA Division I head strength and
      conditioning coach.
AB  - The purpose of this study was to determine the appropriate educational,
      competitive, and work experiences the aspiring strength and conditioning coach
      should attain in pursuit of a head position at the intercollegiate level. The
      study was compared to a doctoral study conducted by Frank Pullo in 1988. Data
      were collected on demographic characteristics, educational background,
      competitive experiences, coaching experiences, duties, and opinions of the head
      strength and conditioning coaches in the National Collegiate Athletic Association
      Division I intercollegiate body. These data were used to determine if differences
      occurred among the Division I-A, I-AA, and I-AAA coaches on these 6 indicators
      along with comparable items in Pullo's study. A total of 212 of 313 coaches
      returned the questionnaire. Each item on the questionnaire was examined with
      either descriptive statistics or frequency distributions. The results indicated
      that differences occurred among the 3 Division I subdivisions and between this
      study and Pullo's study along the 6 indicators measured.

PMID- 14971990
TI  - Self-reported training methods of mixed martial artists at a regional reality
      fighting event.
AB  - This study surveyed 28 athletes competing at a regional mixed martial arts (MMA)
      event. The survey attempted to gather information regarding overall training
      volume, supplement use, and specific exercises used. The survey return rate was
      100% (28/28). Twenty-five out of the 28 athletes supplemented their training with
      strength training. Overall frequency of strength training sessions/week ranged
      from 1-7, and overall frequency of fighting specific training sessions/week
      ranged from 3-12. Five out of the 28 athletes used/had used anabolic-androgenic
      steroids. Twelve of the MMA athletes did not perform exercises specifically for
      the neck musculature, and only 8 used the power clean and/or power snatch within
      their strength-training program. The results suggest that strength and
      conditioning specialists should educate MMA athletes regarding the importance of
      balanced training, effective exercises, and the side effects of anabolic
      androgenic steroid use.

PMID- 14971991
TI  - Tissue trauma: the underlying cause of overtraining syndrome?
AB  - An athlete who trains intensely, yet consistently underperforms, is considered to
      be suffering from overtraining syndrome (OTS). OTS is a complex state that
      involves a large variety of signs and symptoms. Symptoms include changes in mood
      or behaviour, decreases or increases in concentration of different blood
      molecules, and alterations in immune function. Although several hypotheses have
      been proposed, each only explains a selective aspect of OTS. Presently, the sole
      agreement is that OTS is associated with excessive training and insufficient rest
      and recovery. The hypothesis proposed in this paper suggests that excessive
      training/competing causes repetitive tissue trauma, either to muscle and/or
      connective tissue and/or to bony structures, and that this results in chronic
      inflammation. It is further proposed that traumatized tissue synthesizes a group
      of inflammatory molecules, cytokines. Cytokines have been shown to coordinate the
      different systems of the body to promote recovery. Suggestions are made to
      detect, prevent, and rehabilitate the overtrained athlete.

PMID- 14971992
TI  - Capsule endoscopy: a new era in the history of endoscopy.

PMID- 14971993
TI  - Usefulness of capsule endoscopy in patients with suspected small bowel disease.
AB  - AIM: To study the usefulness and safety of capsule endoscopy as a diagnostic tool
      in various small bowel disorders. DESIGN: A retrospective analysis of a series of
      cases. MATERIAL AND METHODS: Between August 2001 and August 2002, 92 capsule
      endoscopy procedures were performed in 88 patients (53M/39F, age: 43.87 +/-
      16.78). Indications included: chronic diarrhea (n=33); unknown abdominal pain
      (n=29); occult gastrointestinal bleeding or iron-deficiency anemia (n=13);
      abdominal discomfort in NSAID takers (n=7); staging of gastrointestinal tumors
      (n=4), and asymptomatic controls (n=2). Previously performed gastroscopy,
      colonoscopy, and small-bowel follow-through were not conclusive in all patients.
      RESULTS: Most frequently relevant findings included: jejuno-ileal aphtas and
      ulcerations (29 patients), vascular malformations (13 patients), and intestinal
      neoplasm (6 patients). The groups with a higher rate of findings related to this
      indication were occult gastrointestinal bleeding (76.92%) and chronic diarrhea
      (67.85%), with the lowest rate in the abdominal pain group (34.48%). Therapeutic
      strategy was directly changed in 36 of 88 patients (40.90%) because of capsule
      endoscopic findings. The only observed complication was the failed excretion of
      one of the capsules because of an unknown ulcerated intestinal stricture.
      CONCLUSIONS: Capsule endoscopy is a safe procedure which can study the entire
      small bowel, meaning a valuable tool for the management of patients with
      suggestive signs and symptoms of intestinal disorders.

PMID- 14971994
TI  - Liver transplantation in patients with hepatocellular carcinoma: factors
      implicated in tumor relapse.
AB  - INTRODUCTION: Liver segmental resection and liver transplantation are both
      treatments intended for healing liver cancer. An adequate selection of patients
      eligible for transplantation is crucial, since organs available for transplants
      are usually scarce. For this reason, awareness of the prognostic factors of
      relapse is of great importance. We present a comprehensive review of our series
      in order to better understand these prognostic factors. MATERIAL AND METHODS: We
      revised the cases of patients with hepatocellular carcinoma who underwent liver
      transplantation during the period 1994-2000, and present a detailed analysis of a
      series of variables which may be probably implicated in the appearance of relapse
      and which have an effect on survival. RESULTS: After a mean follow-up of 33
      months, the mortality rate was 27.5% and relapse occurred in 18.75% of cases. No
      history of alcohol abuse, the number and size of the nodules, the presence of
      macro and microscopic vascular invasion, and pTNM stage T4 were all factors
      associated with a significantly increased risk of relapse (p<0.05). These factors
      and positive HCV were associated to decreased survival. After a multivariate
      analysis, the size of the nodules and the presence of macroscopic vascular
      invasion were considered the only independent risk factors for tumor relapse and
      post-transplantation relapse and mortality, respectively. CONCLUSIONS:
      Macroscopic vascular invasion and tumor nodules larger than 5 cm are both
      independent risk factors of tumor relapse after transplantation. Nevertheless,
      only macroscopic vascular invasion seems to have a significant effect on
      survival.

PMID- 14971995
TI  - Our sigmoid colon volvulus experience and benefits of colonoscope in detortion
      process.
AB  - BACKGROUND/AIMS: The sigmoid colon is the most frequent site for a volvulus. In
      this report, we review our experience with sigmoid colon volvulus. METHODOLOGY:
      We present our experience of 81 cases of sigmoid volvulus admitted to our
      department. RESULTS: Preoperative endoscopic volvulus detortion was attempted in
      all patients, and in 39 of them the procedure was successful. The success rate of
      endoscopic detortion for sigmoid colon volvulus with a flexible colonoscope (60%)
      was higher than with a rigid rectosigmoidoscope (42%). In 19 of these 39 non
      operatively devolvulated patients, sigmoid resection with primary anastomosis was
      performed within 7-10 days after reduction, but 20 patients did not accept the
      elective operation after a non-operative treatment. Among the 61 patients
      undergoing urgent or elective operation for sigmoid volvulus, there were 17
      laparotomies with only detortion, 19 resections with elective anastomosis, 6
      resections with primary anastomosis, and 19 resections with a Hartmann's pouch.
      There were 9 deaths (21%) among 42 patients who underwent an emergency operation,
      and one (5.2%) among the 19 patients who had elective surgery died because of a
      cerebral embolus. CONCLUSIONS: Initial therapy with endoscopy affords
      decompression and an adequate preparation of patients for surgical resection, and
      a flexible colonoscope has notable advantages over rigid instruments for the
      detortion process.

PMID- 14971996
TI  - Endoscopic resection of large colorectal polyps.
AB  - BACKGROUND: Endoscopic polypectomy is a common technique, but there are
      discrepancies over which treatment--surgical or endoscopic--to follow in case of
      polyps of 2 cm or larger. OBJECTIVES: To analyse the efficacy and complications
      of colonoscopic polypectomy of large colorectal polyps. PATIENTS AND METHODS: 147
      polypectomies were performed on 142 patients over an eight-year period. The
      technique used was that of submucosal adrenaline 1:10000 or saline injection at
      the base of the polyp, followed by resection of the polyp using a diathermic
      snare in the smallest number of fragments. Remnant adenomatous tissue was
      fulgurated with an argon plasma coagulator. Lately, prophylactic hemoclips have
      been used for thick-pedicle polyps. Complete removal was defined as when a polyp
      was completely resected in one or more polypectomy sessions. Polypectomy failure
      was defined as when a polyp could not be completely resected or contained an
      invasive carcinoma. RESULTS: The mean patient age was 67.9 years (range, 4-90
      years), with 68 men and 79 women. There were 74 sessile polyps, and the most
      common location was the sigmoid colon. The most frequent histology was
      tubulovillous. Most of the polyps (96.6%), were resected and cured. This was not
      achieved in four cases of invasive carcinoma, and a villous polyp of the cecum.
      All pedunculated polyps were resected in one session, whereas the average number
      of colonoscopies for sessile polyps was 1.35 +/- 0.6 (range, 1-4). The
      polypectomy was curative in all of the in situ carcinomata except one. As for
      complications, 2 colonic perforations (requiring surgery) and 8 hemorrhages
      appeared, which were controlled via endoscopy. There was no associated mortality.
      CONCLUSIONS: Endoscopic polypectomy of large polyps (> or =2 cm) is a safe,
      effective treatment, though it is not free from complications. Complete resection
      is achieved in a high percentage, and there are few relapses. It should be
      considered a technique of choice for this type of polyp, except in cases of
      invasive carcinoma.

PMID- 14971997
TI  - Molecular genetics of colorectal cancer.
AB  - Colorectal tumours constitute an excellent system to study carcinogenesis and the
      molecular events implicated in the development of cancer. Attending to the way it
      is transmitted, colorectal cancer may appear in one of three forms: sporadic,
      familial, and hereditary. The sporadic form is most common and has no familial or
      hereditary associated factor thus far, while familial and hereditary forms show
      the same inheritance pattern. Hereditary colorectal cancers develop by means of
      defined stages that go from lesions in the crypt of the colon through adenomas to
      manifest cancer. They are characterised by the accumulation of multiple mutations
      in tumour suppressor genes and oncogenes that affect the balance between cell
      proliferation and apoptosis. The colorectal carcinogenesis pathway is not unique
      and there are probably several ways for the initiation, development and
      progression of colorectal tumours.

PMID- 14971998
TI  - Diagnostic and therapeutic approach to cholestatic liver disease.
AB  - When cholestatic liver disease is present, liver ultrasound should be performed
      to ascertain if cholestasis is extrahepatic or intrahepatic. If bile ducts appear
      dilated and the probability of interventional treatment is high, endoscopic
      retrograde cholagio-pancreatography (ERCP) or trans-hepatic cholangiography (THC)
      should be the next step. If the probability of interventional therapeutics is
      low, cholangio-MRI should be performed. Once bile duct dilation and space
      occupying lesions are excluded, a work up for intrahepatic cholestasis should be
      started. Some specific clinical situations may be helpful in the diagnostic
      strategy. If cholestasis occurs in the elderly, drug-induced cholestatic disease
      should be suspected, whereas if it occurs in young people with risk factors,
      cholestatic viral hepatitis is the most likely diagnosis. During the first
      trimester of pregnancy cholestasis may occur in hyperemesis gravidorum, and in
      the third trimester of gestation cholestasis of pregnancy should be suspected. A
      familial history of recurrent cholestasis points to benign recurrent intrahepatic
      cholestasis. The occurrence of intrahepatic cholestasis in a middle-aged woman is
      a frequent presentation of primary biliary cirrhosis, whereas primary sclerosing
      cholangitis should be suspected in young males with inflammatory bowel disease.
      The presence of vascular spider nevi, ascites, and a history of alcohol abuse
      should point to alcoholic hepatitis. Neonatal cholestasis syndromes include CMV,
      toxoplasma and rubinfections or metabolic defects such as cystic fibrosis, alpha1
      antitrypsin deficiency, bile acid synthesis defects, or biliary atresia. The
      treatment of cholestasis should include a management of complications such as
      pruritus, osteopenia and correction of fat soluble vitamin deficiencies. When
      hepatocellular failure or portal hypertension-related complications occur, liver
      transplantation should be considered.

PMID- 14971999
TI  - Caroli's syndrome and imaging: report of a case.

PMID- 14972000
TI  - Gastrointestinal hemorrhage due to metastatic choriocarcinoma with gastric and
      colonic involvement.
AB  - Metastatic choriocarcinoma is a rare nonseminomatous germ-cell tumor with a
      characteristic hemorrhagic tendency due to its trophoblastic origin.
      Gastrointestinal tube involvement is present in less than 5% of cases, and
      location or therapy of these lesions can be achieved by endoscopy, angiography or
      surgery. Despite its being a highly curable malignant disease, the occurrence of
      gastrointestinal bleeding worsens prognosis. We report a case of metastatic
      choriocarcinoma which manifested as melaena and was diagnosed by the presence of
      metastatic lesions in the stomach and right bowel on endoscopy.

PMID- 14972001
TI  - [Primary gastric lymphoma and acute gastrointestinal bleeding].

PMID- 14972002
TI  - [Cecal volvulus in Cornelia de Lange syndrome].

PMID- 14972003
TI  - [Iron overload and chronic hepatitis C: the role of HFE gene mutations].

PMID- 14972004
TI  - [HFE gene mutations, hepatic iron content, and histological severity in hepatitis
      C virus-induced chronic hepatitis].
AB  - OBJECTIVE: To study whether any relationship exists between the C282Y and H63D
      mutations of the HFE gene, iron liver content, and the severity of histological
      damage in patients with hepatitis C virus (HCV)-induced chronic hepatitis.
      MATERIAL AND METHODS: In 72 patients diagnosed with HCV-chronic infection, naive
      for antiviral therapy, and undergoing liver biopsy, the Knodell index was
      established, a morphometric evaluation of hepatic hemosiderin deposits was
      performed by using a semiautomatic method of image analysis, and mutations of the
      HFE gene were identified through a polymerase chain reaction on leukocyte genomic
      DNA by using specific restriction enzymes. The control group for the distribution
      of HFE genetic variants was composed of 181 healthy individuals with the same
      ethnic and geographical (white Spaniards) origin. RESULTS: (Cases/controls): 1.
      Genotype distribution: a) mutation C282Y: no homozygotes, 6/23 heterozygotes,
      66/158 without the mutation (not significant, n.s.); b) mutation H63D: 2/5
      homozygotes, 26/52 heterozygotes, 44/124 without the mutation (n.s.). compound
      heterozygotes 2/6. 2. Allele frequencies: a) mutation C282Y: 0.042/0.064 (n.s.);
      b) mutation H63D: 0.208/0.171 (n.s.). Four C282Y heterozygous patients had
      stainable liver iron (p=0.015 vs patients without mutations). Sixty-six patients
      were not carriers of the C282Y mutation; among them, 26.9% of 26 carriers and 15%
      of 40 non-carriers of the H63D mutation had liver stainable iron (n.s.). Knodell
      index score, gender, age at diagnosis, mode of transmission, and serum and liver
      iron values were not related to the HFE genotype. CONCLUSIONS: our results
      suggest that the C282Y mutation, but not the H63D mutation, of the HFE gene is
      frequently associated with stainable iron in the liver in HCV-related chronic
      hepatitis. The HFE genotype is not related to the histological severity of the
      disease.

PMID- 14972005
TI  - [Advanced gastric cancer: characteristics at presentation and therapeutic
      possibilities].
AB  - OBJECTIVE: To analyse the presentation forms and prognosis of patients with
      advanced gastric cancer at the time of diagnosis. DESIGN: Retrospective cohort
      study. PATIENTS AND METHODS: We studied all patients with gastric cancer
      (n=2,334) and synchronic metastases diagnosed in Lugo and A Coruna hospitals
      between 1975 and 1993. We estimated survival probability using the Kaplan-Meier
      method, and prognostic factors with Cox's regression models. RESULTS: Metastases
      were detected at the time of diagnosis in 585 (25.1%) patients, with the liver
      (346; 14.8%) and peritoneum (61; 6.9%) being the most frequently involved sites.
      The liver was exclusively affected in 213 (9.1%) cases, the peritoneum in 70
      (3.3%), and another intraabdominal site in 121 (5.2%). Patients with peritoneal
      metastases were older (p=0.05), more commonly had a diffuse type of cancer
      according to Lauren's tumor classification (p<0.001), and underwent surgery more
      frequently (p=0.01). Curative resection was possible for only 11 (5.2%), 7 (10%),
      and 25 (20.7%) patients with metastases in only the liver, peritoneum, or another
      site, respectively, but in all cases survival probability was significantly
      enhanced. No surgery (HR=2.92), and simultaneous involvement of the liver and
      peritoneum (HR=1.62) were factors associated with a higher mortality rate.
      CONCLUSIONS: Patients with gastric cancer and metastases in only one
      intraabdominal organ show characteristic forms of presentation. Furthermore, in
      all cases candidacy for surgery should be carefully evaluated, as prognosis may
      improve in selected patients.

PMID- 14972006
TI  - [Levels of satisfaction and perceived quality in a day surgery unit of a tertiary
      referral hospital].
AB  - INTRODUCTION: Surgical and anesthetic advances have allowed an adequate develop
      at the day surgery programs, with a rational application and cost-effectiveness
      of the hospital resorts. The aim of this study, is to know the level of quality
      perceived in surgical treatment in a program of day surgery. MATERIAL AND
      METHODS: A randomised selection of 204 patients from a series of 751 operated,
      between April-May 2001 in a day-surgery institution, was done. Phone
      questionnaire was done following protocol SERCAL (sociodemographic factors and
      general satisfaction, accessibility, personal assistance, guarantee and fidelity
      service) with validation for day surgery programs. Absolute and relatives
      frequencies were evaluated for dichotomous and categoric variables and medium and
      standard deviation for numeric variables. Possible differences were evaluated by
      chi2 test in qualitative variables and Student's t and ANOVA test for
      quantitative variables. RESULTS: Response index was 70.1%. Satisfaction general
      index was 9.1%, for 18 numeric items (range 0-10). Social and demographic items
      show that the best validity of treatment were by elderly, women, retired and low
      cultural patients. Data reduction by factorial analysis showed 4 factors with
      incidence (total variance 71.62%): Scientific-technical guarantee service and
      adequate personal treatment (Cronbach's alpha 0.9060), comfortable and security
      assistance (Cronbach's alpha 0.8708), accessibility to hospital and professionals
      (Cronbach's alpha 0.0652), accessibility to surgical service. CONCLUSIONS:
      General satisfaction of the patients treated in the day-surgery program was high,
      9.1 (range 0-10). 88.8% patients would recommend this type of treatment to their
      parents or friends and in 84.3% would repeat the same experience in the surgery
      unit. The best appreciate items were the direct treatment and relation, respect,
      intimacy and information along the assistential circuit by implicated
      professionals. The worst identified item was the time past in waiting surgical
      list.

PMID- 14972007
TI  - [Electrolytic disturbances and colonoscopy: bowel lavage solutions, age and
      procedure].
AB  - INTRODUCTION: Colonoscopy and bowel preparation cause a number of serum
      electrolytes changes. AIMS: To determine the prevalence of these changes in
      patients who underwent colonoscopy and to identify risk factors for these
      effects. PATIENTS AND METHODS: Forty five patients undergoing colonoscopy were
      assessed prospectively. They have been previously randomized to receive either
      sodium phosphate (NaP) or polyethylene glycol (PEG) as preparation. Serum levels
      of sodium and potassium were analyzed before colonoscopy, immediately after the
      end of colonoscopy, and 1 hour thereafter. Serum calcium and phosphorus levels
      were measured just before colonoscopy. RESULTS: Twenty five patients (55.5%)
      received PEG and 17 (37.7%) NaP. Three patients (6.6%) did not follow the
      recommended bowel preparation instructions and were excluded from the study. Five
      patients (11%) developed hyponatremia, of whom, in 4 cases (8.8%), it occurred
      after the procedure. Thirteen patients (28.8%) developed hypokalemia, of whom it
      occurred after the end of the procedure in seven (15.5%). There was a non
      significant trend to decreased serum potassium levels 1 hour after colonoscopy in
      patients prepared with NaP (63.6 vs 36.4%). The multivariate analysis showed that
      low potassium levels were independently associated with age and NaP preparation.
      Hypocalcemia was observed in 2 patients (4%) and hypophosphatemia in 8 (18%).
      Hyperphosphatemia was found in 8 cases (18%). Non-significant increases in
      phosphorus levels were observed in the NaP group. CONCLUSIONS: Temporal sequences
      of the development of serum electrolyte disturbances suggest that colonoscopy
      itself might play a role in the pathogenesis of these changes. Preparation for
      colonoscopy with NaP and the age of patients are risk factors for the development
      of hypokalemia.

PMID- 14972008
TI  - [Indications and therapeutic possibilities of albumin dialysis (MARS)].
AB  - Despite remarkable medical advances during the last few years, liver failure-
      both acute and chronic--still results in high mortality. Since liver transplant
      programs were developed to improve survival in numerous hepatic end-stage
      disorders, fewer than 15% of patients with liver failure do actually receive a
      transplantation, be it because of the presence of procedural contraindications
      (toxic habits, age, concurrent disease), or of clinical conditions that may
      render surgery more difficult or worsen transplant prognosis. All these
      circumstances encouraged the development of alternative procedures to increase
      liver graft availability, as is the case of liver partition techniques and living
      donor transplantation. On the other hand, organ scarcity for transplantation
      during the 1960s encouraged the parallel development of liver support systems in
      an attempt to reduce mortality and to improve patient survival while waiting for
      a transplant. Such systems attempt to replace a number of synthesis and
      detoxification functions for the damaged liver parenchyma. During the past few
      years both bioartificial systems--also referred to as "bioartificial livers"-
      based on bioreactors containing functionally active living hepatocytes, and
      extracorporeal liver detoxification systems have been developed. The latter type
      includes the so-called MARS (molecular adsorbent recirculating system) system,
      which combines albumin-bound molecule clearance and novel dialysis membrane
      biocompatibility.

PMID- 14972009
TI  - [Pancreatic acinar metaplasia in Barrett's esophagus after antireflux surgery].

PMID- 14972010
TI  - [Actinomycosis of the appendix].

PMID- 14972011
TI  - Properties, functions, and secretion of human myeloperoxidase.
AB  - The heme-containing protein myeloperoxidase is released from stimulated
      polymorphonuclear leukocytes at sites of inflammation. It is involved in the
      generation of reactive oxygen and nitrogen species and tissue damage. The general
      properties and functional aspects of this enzyme are reviewed. Special attention
      is given to luminescence methods for investigating the release of myeloperoxidase
      from stimulated cells.

PMID- 14972012
TI  - Conversion of death signal into survival signal by redox signaling.
AB  - Reperfusion of ischemic myocardium produces reactive oxygen species (ROS) and
      results in apoptotic cell death and DNA fragmentation. Several redox-sensitive
      anti- and pro- apoptotic transcription factors including nuclear factor kappaB
      (NF-kappaB) and heterodimeric transcription factor AP-1 progressively and
      steadily increase in the heart as a function of the duration of ischemia and
      reperfusion. When the heart is adapted to ischemic stress by repeated short-term
      ischemia and reperfusion, NF-kappaB remains high, while AP-1 is lowered to almost
      baseline value. The anti-apoptotic gene Bcl-2 is downregulated in the
      ischemic/reperfused heart, while it is upregulated in the adapted myocardium.
      Cardioprotective abilities of the adapted myocardium are abolished when heart is
      pre-perfused with N-acetyl cysteine to scavenge ROS, suggesting a role of redox
      signaling. Mammalian heart is protected by several defense systems, which
      include, among others, the redox-regulated protein thioredoxin. Reperfusion of
      ischemic myocardium results in the downregulation of thioredoxin 1 (Trx 1)
      expression, which was upregulated in the adapted myocardium. The increased
      expression of Trx 1 is completely blocked with an inhibitor of Trx 1, cis
      diammine-dichloroplatinum, which also abolished cardioprotection afforded by
      ischemic adaptation. The cardioprotective role of Trx 1 is further confirmed with
      transgenic mouse hearts overexpressing Trx 1. The Trx 1 mouse hearts displayed
      significantly improved post-ischemic ventricular recovery and reduced myocardial
      infarct size and apoptosis compared to the corresponding wild-type mouse hearts.
      The results of this study implicate a crucial role of redox signaling in
      transmitting anti-death signal.

PMID- 14972013
TI  - Oxidative stress promotes the regression of fetal liver hemopoiesis.
AB  - Although apoptosis is believed to play an important role in the ontogenetic
      development of animals, the molecular mechanism that triggers the regression of
      liver hemopoiesis during the perinatal period is not known. Apoptosis is induced
      by many factors such as a decrease in growth factors and increased oxygen stress.
      Since hepatic gamma-glutamyl transferase (GT) levels change markedly during the
      perinatal period in rodents, the metabolism of glutathione (GSH), a naturally
      occurring major antioxidant, might change significantly in and around liver
      cells. Hemopoietic cells but not hepatocytes exhibit significant apoptosis in
      thiol-free medium and the hemopoietic apoptosis can be inhibited by various
      thiols, such as L-cysteine, N-acetyl-L-cysteine, and GSH. The contribution of GSH
      levels in and around fetal liver cells in the triggering of apoptosis in
      hemopoietic cells is discussed.

PMID- 14972014
TI  - Pro/antioxidant status in murine skin following topical exposure to cumene
      hydroperoxide throughout the ontogeny of skin cancer.
AB  - Organic peroxides used in the chemical and pharmaceutical industries have a
      reputation for being potent skin tumor promoters and inducers of epidermal
      hyperplasia. Their ability to trigger free radical generation is critical for
      their carcinogenic properties. Short-term in vivo exposure of mouse skin to
      cumene hydroperoxide (Cum-OOH) causes severe oxidative stress and formation of
      spin-trapped radical adducts. The present study was designed to determine the
      effectiveness of Cum-OOH compared to 12-O-tetradecanoylphorbol-13-acetate (TPA)
      in the induction of tumor promotion in the mouse skin, to identify the
      involvement of cyclooxygenase-2 (COX-2) in oxidative metabolism of Cum-OOH in
      keratinocytes, and to evaluate morphological changes and outcomes of oxidative
      stress in skin of SENCAR mice throughout a two-stage carcinogenesis protocol.
      Dimethyl-benz[a]anthracene (DMBA)-initiated mice were treated with Cum-OOH (32.8
      micro mol) or TPA (8.5 nmol) twice weekly for 20 weeks to promote papilloma
      formation. Skin carcinoma formed only in DMBA/Cum-OOH-exposed mice. Higher levels
      of oxidative stress and inflammation (as indicated by the accumulation of
      peroxidative products, antioxidant depletion, and edema formation) were evident
      in the DMBA/Cum-OOH group compared to DMBA/TPA treated mice. Exposure of
      keratinocytes (HaCaT) to Cum-OOH for 18 h resulted in expression of COX-2 and
      increased levels of PGE(2). Inhibitors of COX-2 efficiently suppressed oxidative
      stress and enzyme expression in the cells treated with Cum-OOH. These results
      suggest that COX-2-dependent oxidative metabolism is at least partially involved
      in Cum-OOH-induced inflammatory responses and thus tumor promotion.

PMID- 14972015
TI  - Role of nitric oxide in the progression of pneumoconiosis.
AB  - Conflicting evidence has been reported as to whether nitric oxide (NO) possesses
      anti-inflammatory or inflammatory properties. Data are presented indicating that
      in vitro or in vivo exposure to selected occupational dusts, i.e., crystalline
      silica, organic dust contaminated with endotoxin, or asbestos, results in
      upregulation of inducible nitric oxide synthase (iNOS) and the production of NO
      by alveolar macrophages and pulmonary epithelial cells. Nitric oxide production
      is associated temporally and anatomically with pulmonary damage, inflammation,
      and disease progression in response to occupational dusts. Blockage of inducible
      nitric oxide synthase by administration of NOS inhibitors or in iNOS knockout
      mice decreases the magnitude of injury and inflammation following in vivo
      exposure to silica, endotoxin, or asbestos. Therefore, NO may play an important
      role in the initiation and progression of pneumoconiosis.

PMID- 14972016
TI  - Exploiting oxidative stress and signaling in chemotherapy of resistant neoplasms.
AB  - Neural crest tumors of childhood are particularly resistant to apoptosis
      induction by chemotherapeutic agents. Mechanisms of resistance include altered
      glutathione handling that accompanies up-regulation of Bcl-2 and its relatives.
      We have designed and tested in preclinical model systems approaches to this
      problem. These approaches include adjunctive use of oxygen radical-generating
      neurotransmitter analogs taken up by these neural crest tumor cells with
      scavenging (i.e., "rescue") agents that are selective for normal neural crest and
      the use of reduction-dependent prodrugs of apoptosis-inducing agents. Promising
      prototypes for these conceptual approaches include, respectively, adjunctive use
      of the oxygen radical generator, 6-hydroxydopamine, with the normal cell
      selective antioxidant, Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl),
      and use of the reduction-dependent chemotherapeutic prodrug neocarzinostatin.

PMID- 14972017
TI  - Modality of cell death induced by Foscan-based photodynamic treatment in human
      colon adenocarcinoma cell line HT29.
AB  - Apoptosis induced by photodynamic therapy (PDT) is considered to be an important
      factor defining the treatment outcome. Nevertheless, the relevance of apoptotic
      events in overall cell death should be established for every given
      photosensitizer. The present study addresses the contribution of Foscan-(meta
      tetra(hydroxyphenyl)chlorine; mTHPC) photosensitized apoptosis in overall cell
      death in a model of cultured HT29 adenocarcinoma cells. Early events of cell
      death were assessed by the evaluation of mitochondrial response to mTHPC-mediated
      PDT, cytochrome c release and membrane depolarization. Apoptosis was measured
      through the activity of caspase-3 and the binding of the fluorescent conjugate
      Ca2+-dependent protein Annexin-V on membrane externalized phosphatidylserine at
      2, 4, and 24 h post-PDT. Immediately after mTHPC-PDT, from 28 to 57% cells
      exhibited cytochrome c release concomitantly with mitochondrial membrane
      depolarization for light doses inducing more than 90% overall cell death. The
      maximum of caspase-3 activation (12-fold more than control) was reached 24 h
      after irradiation at fluence inducing 90% cell death (LD(90)). The corresponding
      measurement of apoptotic cells (12% of Annexin-V bound cells) confirmed the mild
      and delayed apoptotic response of HT29 cells to mTHPC-PDT.

PMID- 14972018
TI  - Enhancement of nitric oxide and superoxide generations by alpha-tocopheryl
      succinate and its apoptotic and anticancer effects.
AB  - Tocopheryl succinate (TS), a succinyl ester of alpha-tocopherol (alpha-T), has
      been reported to have various biological activities. In this communication, we
      review the current findings about TS including our recent studies of its effects
      on nitric oxide (NO) and superoxide (O2-) generations implicated in cancer and
      atherosclerosis. First, we investigated the effect of TS on NO production in
      vascular smooth muscle cells (VSMC) under atherosclerosis-like conditions using
      lipopolysaccharide (LPS) and interferon-gamma (IFN). TS enhanced LPS/IFN
      dependent NO production, but alpha-T itself did not. The enhancement by TS of NO
      production was inhibited by alpha-T but not by antioxidants such as ascorbic acid
      and 2[3]-t-butyl-4-hydroxyanisole (BHA). TS enhanced the amount of protein kinase
      Calpha (PKCalpha) in VSMC, and PKC inhibitors inhibited TS-enhanced NO
      production, suggesting that the enhancing effect of TS on NO production is caused
      by up-regulation of PKC. Second, we found that TS induced apoptosis in VSMC
      associated with increase in O2- generation via NADPH-dependent oxidase. We
      further observed that a mouse breast cancer cell line C127I was more susceptible
      for TS-induced apoptosis than a mouse breast normal cell line NmuMG, and that
      superoxide dismutase, alpha-T, and BHA inhibited TS-caused morphological cell
      damage in C127I. From these results, O2- itself and/or other reactive oxygen
      species are assumed to associate with TS-induced cell toxicity, and antioxidative
      defense systems are supposed to be lowered in cancer cells. Finally, we found
      that intravenous injection of TS vesicles completely inhibited the growth of
      melanoma cells B16-F1 inoculated on the back of hairless mice and enhanced their
      survival time.

PMID- 14972019
TI  - Is the distribution of alpha-tocopherol in membranes consistent with its putative
      functions?
AB  - Vitamin E acts as an antioxidant and stabilizer of membranes. Other functions of
      vitamin E unrelated to its effects on membranes are emerging. Vitamin E
      partitions into the lipid bilayer matrix of membranes. It orients perpendicularly
      to the plane of the membrane with the hydroxyl group pointing to the lipid-water
      interface. The vitamin is not randomly distributed in the plane of the membrane
      but tends to form clusters. These clusters appear to be composed of vitamin E and
      phosphatidylcholine in a stoichiometry of about one vitamin E per 10 phospholipid
      molecules. Vitamin E partitions into domains of phosphatidylcholine in model
      membranes formed from mixtures of phosphatidylcholine and
      phosphatidylethanolamine irrespective of whether the phosphatidylcholine is in
      the fluid or gel phase. The creation of domains enriched in vitamin E in
      membranes is not consistent with an antioxidant function and effects on membrane
      structure and stability indicate other roles of the vitamin.

PMID- 14972020
TI  - Anti-angiogenic potential of tocotrienol in vitro.
AB  - Modulation of angiogenesis is now a recognized strategy for the prevention of
      various angiogenesis-mediated disorders. We investigated, using well
      characterized in vitro systems, the anti-angiogenic property of vitamin E
      compounds, with particular emphasis on tocotrienol, a natural analog of
      tocopherol. Tocotrienol, but not tocopherol, inhibited the proliferation of
      bovine aortic endothelial cells in dose dependent manner at half-maximal
      concentrations in the low micromolar range. Tocotrienol also significantly
      inhibited the formation of networks of elongated endothelial cells within 3D
      collagen gels. From these results, we suggest that tocotrienol is a potential
      candidate for the development of useful therapeutic agents or preventive food
      factors for tumor angiogenesis.

PMID- 14972021
TI  - Effects of coffee consumption on oxidative susceptibility of low-density
      lipoproteins and serum lipid levels in humans.
AB  - Since little is known about how coffee intake affects low-density lipoprotein
      (LDL) oxidative susceptibility and serum lipid levels, we conducted an in vivo
      study in 11 healthy male students of Wakayama Medical University aged between 20
      and 31 years fed an average Japanese diet. On days 1-7 of the study, the subjects
      drank mineral water. On day 7, the subjects began drinking coffee, 24 g total per
      day, for one week. This was followed by a one week "washout period" during which
      mineral water was consumed. Fasting peripheral venous blood samples were taken at
      the end of each one-week period. LDL oxidation lag time was approximately 8%
      greater (p < 0.01) after the coffee drinking period than the other periods. Serum
      levels of total cholesterol and LDL-cholesterol (LDL-C) and malondialdehyde (MDA)
      as thiobarbituric acid reactive substances (TBARS) were significantly decreased
      after the coffee drinking period. Finally, regular coffee ingestion may favorably
      affect cardiovascular risk status by modestly reducing LDL oxidation
      susceptibility and decreasing LDL-cholesterol and MDA levels.

PMID- 14972022
TI  - Anti-angiogenic, antioxidant, and anti-carcinogenic properties of a novel
      anthocyanin-rich berry extract formula.
AB  - Edible berry anthocyanins possess a broad spectrum of therapeutic and anti
      carcinogenic properties. Berries are rich in anthocyanins, compounds that provide
      pigmentation to fruits and serve as natural antioxidants. Anthocyanins repair and
      protect genomic DNA integrity. Earlier studies have shown that berry anthocyanins
      are beneficial in reducing age-associated oxidative stress, as well as in
      improving neuronal and cognitive brain function. Six berry extracts (wild
      blueberry, bilberry, cranberry, elderberry, raspberry seeds, and strawberry) were
      studied for antioxidant efficacy, cytotoxic potential, cellular uptake, and anti
      angiogenic (the ability to reduce unwanted growth of blood vessels, which can
      lead to varicose veins and tumor formation) properties. We evaluated various
      combinations of edible berry extracts and developed a synergistic formula,
      OptiBerry IH141, which exhibited high ORAC (Oxygen-Radical Absorbing Capacity)
      value, low cytotoxicity, and superior anti-angiogenic properties compared to the
      other combinations tested. Anti-angiogenic approaches to treat cancer represent a
      priority area in vascular tumor biology. OptiBerry significantly inhibited both
      H2O2- and TNF-alpha-induced VEGF (Vascular Endothelial Growth Factor) expression
      by human keratinocytes. VEGF is a key regulator of tumor angiogenesis. Matrigel
      assay using human microvascular endothelial cells showed that OptiBerry impaired
      angiogenesis. In an in vivo model of angiogenesis, OptiBerry significantly
      inhibited basal MCP-1 and inducible NF-kappaB transcriptions. Endothelioma cells
      pretreated with OptiBerry showed a diminished ability to form hemangioma and
      markedly decreased tumor growth by more than 50%. In essence, these studies
      highlight the novel anti-angiogenic, antioxidant, and anti-carcinogenic potential
      of a novel anthocyanin-rich berry extract formula, OptiBerry.

PMID- 14972023
TI  - Photobiological principles of therapeutic applications of laser radiation.
AB  - Laser therapy based on the stimulating and healing action of light of low
      intensity lasers (LIL), along with laser surgery and photodynamic therapy, has
      been lately widely applied in the irradiation of human tissues in the absence of
      exogenous photosensitizers. Besides LIL, light-emitting diodes are used in
      phototherapy (photobiostimulation) whose action, like that of LIL, depends on the
      radiation wavelength, dose, and distribution of light intensity in time but,
      according to all available data, does not depend on the coherence of radiation.

PMID- 14972024
TI  - Mitochondrial calcium transport systems: properties, regulation, and taxonomic
      features.
AB  - Currently available information on properties and regulation of mitochondrial
      Ca2+ transporting systems in eukaryotic cells is summarized. We describe in
      detail kinetic properties and effects of inhibitors and modulators on the energy
      dependent Ca2+ uptake through the Ca2+ uniporter, as well as on Na+-dependent and
      Na+-independent pathways for Ca2+ release in mammalian mitochondria. Special
      emphasis is placed on Ca2+ transport systems (for ion uptake and release) in
      mitochondria of higher plants, algae, and yeasts. Potential physiological
      implications of mitochondrial Ca2+ fluxes (influx and efflux), e.g., regulation
      of activity of Ca2+-dependent enzymes of the Krebs cycle, maintaining of cellular
      Ca2+ homeostasis, and engagement in pathophysiological processes, are discussed.

PMID- 14972025
TI  - D- and L-aspartic acids: new non-sugar components of bacterial polysaccharides.
AB  - For the first time in bacterial polysaccharides, residues of D- and L-aspartic
      acids were identified as N-acyl substituents of 4-amino-4,6-dideoxy-D-glucose in
      the O-antigens of enterobacteria of the genera Providencia and Proteus.

PMID- 14972027
TI  - The active site and substrate-binding mode of 1-aminocyclopropane-1-carboxylate
      oxidase determined by site-directed mutagenesis and comparative modelling
      studies.
AB  - The active site and substrate-binding mode of MD-ACO1 (Malus domestica Borkh. 1
      aminocyclopropane-1-carboxylate oxidase) have been determined using site-directed
      mutagenesis and comparative modelling methods. The MD-ACO1 protein folds into a
      compact jelly-roll motif comprised of eight a-helices, 12 b-strands and several
      long loops. The active site is well defined as a wide cleft near the C-terminus.
      The co-substrate ascorbate is located in cofactor Fe2+-binding pocket, the so
      called '2-His-1-carboxylate facial triad'. In addition, our results reveal that
      Arg244 and Ser246 are involved in generating the reaction product during enzyme
      catalysis. The structure agrees well with the biochemical and site-directed
      mutagenesis results. The three-dimensional structure together with the steady
      state kinetics of both the wild-type and mutant MD-ACO1 proteins reveal how the
      substrate specificity of MD-ACO1 is involved in the catalytic mechanism,
      providing insights into understanding the fruit ripening process at atomic
      resolution.

PMID- 14972026
TI  - Oxidation and reduction of pyridine nucleotides in alamethicin-permeabilized
      plant mitochondria.
AB  - The inner mitochondrial membrane is selectively permeable, which limits the
      transport of solutes and metabolites across the membrane. This constitutes a
      problem when intramitochondrial enzymes are studied. The channel-forming
      antibiotic AlaM (alamethicin) was used as a potentially less invasive method to
      permeabilize mitochondria and study the highly branched electron-transport chain
      in potato tuber (Solanum tuberosum) and pea leaf (Pisum sativum) mitochondria. We
      show that AlaM permeabilized the inner membrane of plant mitochondria to NAD(P)H,
      allowing the quantification of internal NAD(P)H dehydrogenases as well as matrix
      enzymes in situ. AlaM was found to inhibit the electron-transport chain at the
      external Ca2+-dependent rotenone-insensitive NADH dehydrogenase and around
      complexes III and IV. Nevertheless, under optimal conditions, especially complex
      I-mediated NADH oxidation in AlaM-treated mitochondria was much higher than what
      has been previously measured by other techniques. Our results also show a
      difference in substrate specificities for complex I in mitochondria as compared
      with inside-out submitochondrial particles. AlaM facilitated the passage of
      cofactors to and from the mitochondrial matrix and allowed the determination of
      NAD+ requirements of malate oxidation in situ. In summary, we conclude that AlaM
      provides the best method for quantifying NADH dehydrogenase activities and that
      AlaM will prove to be an important method to study enzymes under conditions that
      resemble their native environment not only in plant mitochondria but also in
      other membrane-enclosed compartments, such as intact cells, chloroplasts and
      peroxisomes.

PMID- 14972028
TI  - Partial amino acid sequence and mRNA analysis of cytosolic pyridoxine-beta-D
      glucoside hydrolase from porcine intestinal mucosa: proposed derivation from the
      lactase-phlorizin hydrolase gene.
AB  - We have previously identified and purified a novel beta-glucosidase, designated
      PNGH (pyridoxine-5'-beta-D-glucoside hydrolase), from the cytosolic fraction of
      pig intestinal mucosal. PNGH catalyses the hydrolysis of PNG (pyridoxine-5'-beta
      D-glucoside), a plant derivative of vitamin B6 that exhibits partial nutritional
      bioavailability in humans and animals. Preliminary amino acid sequence analysis
      indicated regions of close similarity of PNGH to the precursor form of LPH
      (lactase-phlorizin hydrolase), the beta-glucosidase localized to the brush-border
      membrane. We report in the present study amino acid sequence data for PNGH and
      results of Northern blot analyses, upon which we propose a common genomic origin
      of PNGH and LPH. Internal Edman sequencing of the PNGH band isolated by SDS/PAGE
      yielded data for 16 peptides, averaging 10.8 amino acids in length. These
      peptides from PNGH (approx. 140 kDa) were highly similar to sequences existing
      over most of the length of the >200 kDa precursor of rabbit LPH; however, we
      found no PNGH sequences that corresponded to approx. 350 amino acids between
      positions 463 and 812 of the LPH precursor, a region encoded by exon 7 of the LPH
      precursor gene (amino acids 568-784), and no sequences that corresponded to
      regions near the N-terminus. MS analysis of tryptic peptides yielded 25 peptides,
      averaging 15 amino acids, with masses that matched segments of the rabbit LPH
      precursor. Northern blot analysis of pig and human small intestinal
      polyadenylated mRNA using a non-specific LPH cDNA probe showed an expected
      approx. 6 kb transcript of the LPH precursor, but also an approx. 4 kb transcript
      that was consistent with the size predicted from the PNGH protein mass. Using a
      probe specific to the region encoded by exon 7, hybridization occurred only with
      the 6 kb transcript. Based on these observations, we propose that both PNGH and
      LPH enzymes have the same genomic origin, but differ in transcriptional and,
      possibly, post-translational processing.

PMID- 14972030
TI  - Hymenolepis microstoma: direct life cycle in immunodeficient mice.
AB  - The mouse bile duct tapeworm Hymenolepis microstoma requires beetles as the
      obligatory intermediate host. However, when congenitally athymic NMRI-nu mice
      were infected with the mature tapeworm and allowed to eat their own faeces with
      tapeworm eggs, the oncospheres penetrated the intestinal tissue and developed to
      cysticercoids. After excysting, growth to adult worms occurs in the lumen of the
      small intestine and bile duct. Furthermore, the same happened when NMRI-nu mice,
      non-obese diabetic severe combined immunodeficiency (NOD/Shi-scid) mice and
      NOD/Shi-scid, IL-2 Rgamma(null) (NOG) mice were orally inoculated with shell-free
      eggs of this parasite. Differences between the cysticercoids of H. microstoma and
      H. nana developed in the mouse intestinal tissues were: (i) the time course for
      the development of fully matured cysticercoids of H. microstoma in mice was about
      11 days but only 4 days for H. nana; and (ii) cysticercoids of H. microstoma
      developed in mice had a tail while those of H. nana had none.

PMID- 14972029
TI  - In vitro elucidation of substrate specificity and bioassay of proprotein
      convertase 4 using intramolecularly quenched fluorogenic peptides.
AB  - The fourth member of Ca2+-dependent mammalian secretory subtilase, PC4
      (proprotein convertase 4), is primarily expressed in testicular germ cell and
      ovarian macrophage. Its role in sperm fertilization and in early embryonic
      development has been demonstrated earlier through several studies, including
      those with PC4 null mice. A number of physiological substrates found in
      reproductive tissues have been postulated or identified for PC4 by various
      biochemical studies. These include growth factors IGF-1 (insulin-like growth
      factor-1) and IGF-2, hormonal polypeptide proPACAP (where PACAP stands for
      pituitary adenylate cyclase-activating polypeptide) and a number of surface
      proteins of ADAM (ADisintegrin And Metalloproteinase-like) family such as ADAM-1
      (fertilin a), ADAM-2 (fertilin b), ADAM-3 (procyritestin) and ADAM-5. To provide
      further evidence in support of this notion and also to study the substrate
      specificity and bioassay of PC4, a series of intramolecularly quenched
      fluorogenic peptides containing the cleavage sites and several mutants were
      prepared. A comparative kinetic analysis and measurement of Vmax (app)/Km (app)
      ratio of these fluorogenic substrates against PC4 and PC7 revealed that the
      mutant variants of h (human) proPACAP and m (mouse) ADAM-5 derived peptides Q
      PACAP141-151-mutant [Abz-141RVKNKGRRI150P151SY(NO2)-A-CONH2] (150A151Y replaced
      by PS) and Q-ADAM-5380-388-mutant [Abz-380E381PKPARRP388RY(NO2)A-CONH2] (381R
      replaced by P) are most efficiently and selectively cleaved by PC4. Using these
      two and Q-IGF-263-71 peptides, we showed that the sperm extract of normal adult
      mice is much higher when compared with that of PC4-null mice. This suggests that
      these fluorogenic peptides are useful for specific bioassay of PC4 activity. In
      addition, kinetic studies with various peptidyl-MCA indicate that the hexapeptide
      Ac-KTKQLR-MCA (where MCA stands for 4-methyl coumaryl-7-amide) is most
      efficiently and selectively cleaved by PC4 at RMCA, making it another effective
      agent for bioassay of PC4 activity. The study concludes that the most probable
      sequence motif for recognition by PC4 is KXKXXR or KXXR, where X is any amino
      acid other than cysteine and that it prefers proline at P3, P5 and/or P2'
      positions. It was also revealed that PC4 is a good candidate processing enzyme
      for growth factors IGF-1 and -2, neuropeptide proPACAP and several ADAM proteins
      such as ADAM-1, -2, -3 and -5.

PMID- 14972031
TI  - Differences and similarities of nurse cells in cysts of Trichinella spiralis and
      T. pseudospiralis.
AB  - The nurse cell in the cyst of Trichinella spiralis comprises at least two kinds
      of cytoplasm, derived from muscle or satellite cells, as indicated by the pattern
      of staining using regular dye (haematoxylin and eosin, or toluidine blue),
      alkaline phosphatase (ALP) expression, acid phosphatase (ACP) expression and
      immunostaining with an anti-intermediate filament protein (desmin or keratin).
      Muscle cells undergo basophilic changes following a T. spiralis infection and
      transform to the nurse cells, accompanied by an increase in ACP activity and the
      disappearance of desmin. Satellite cells are activated, transformed and joined to
      the nurse cells but remain eosinophilic. The eosinophilic cytoplasm is
      accompanied by an increase in desmin and ALP expression but not an increase in
      ACP activity. Differences in the staining results for ALP or ACP suggest that the
      two kinds of cytoplasm have different functions. Trichinella pseudospiralis
      infection results in an increase of ACP activity at a later stage than T.
      spiralis. There is also a difference in the location pattern of ACP in the cyst
      of T. spiralis compared with T. pseudospiralis. In T. spiralis, ACP is diffused
      within the cell, but in T. pseudospiralis, ACP distribution is spotty
      corresponding to the location of the nucleus. Trichinella pseudospiralis
      infection is accompanied by a slight increase in ALP activity. Activated
      satellite cells following a T. pseudospiralis infection exhibit an increase in
      desmin expression. The present study therefore reveals that nurse cell cytoplasm
      differs between the two Trichinella species and between the two origins of
      cytoplasm in the cyst of T. spiralis.

PMID- 14972032
TI  - Granulomatous inflammation during Heligmosomoides polygyrus primary infections in
      FVB mice.
AB  - Host responses to primary infections with Heligmosomoides polygyrus were studied
      in fast responding FVB mice (H-2(q)). Pathological changes in the intestinal
      mucosa, mesenteric lymph nodes and spleen were examined. Features of the fast
      response were typical: low effectiveness of infection and limiting of parasite
      survival and egg production, with worm expulsion occurring about 60 days post
      infection. The intestinal inflammatory response involved infiltration by
      different cells into the intestinal mucosa and granulomata formation. As is
      typical for intestinal nematode infection enteropathy, decreased villus:crypt
      ratio and hyperplasia of goblet and Paneth cells were also present. Reactions of
      the intestinal mucosa, mesenteric lymph nodes and spleen increased over time post
      infection and after worm expulsion. Enteropathy may help worm expulsion by
      creating an unfavourable environment for H. polygyrus. The implications of these
      findings and the potential role of intestinal intraepithelial lymphocytes in the
      pathogenesis of generated lesions are discussed.

PMID- 14972033
TI  - Effects of glycine-metal compounds on Ascaridia galli-infected chickens expressed
      by a kinetic model.
AB  - The biogenic elements zinc, manganese and cobalt are essential for metabolic
      processes in animals. Compounds of nGly.Me2+A. mH2O (Me2+=Zn2+, Mn2+, Co2+; A=Cl(
      ), SO4(2-), n=1, 2; m=2, 5), as supplements in the diet, were used separately on
      different experimental groups of male Hisex chickens to correct the mineral
      deficiency caused by Ascaridia galli infections. An amelioration of body weight
      gain, reduction of mortality and restoration of trace element levels were
      estimated in infected chickens. A mathematical model has been proposed for A.
      galli population kinetics in chickens, taking into account the stimulating effect
      of these elements on the nematodes. The model parameters are considered as
      phenomenological constants of the host-parasite system. An agreement with
      experimental data is observed using, for the parameters psi, alpha, micro and
      micros, values equal to those calculated in previously investigated A. galli
      chicken systems. For parameter nu (immunological constant) the same value was
      obtained as in a previous experiment with high infection. This model is likely to
      be suitable for a range of host-nematode systems, including varying degrees of
      infection and treatment with different trace elements.

PMID- 14972034
TI  - Paraspiralatus sakeri n. g., n. sp. (Nematoda: Spiruroidea, Spirocercidae) from
      saker falcons, Falco cherrug in Saudi Arabia and the first report of larvae from
      the subcutaneous tissues of houbara bustards, Chlamydotis undulata macqueeni in
      Pakistan.
AB  - A new nematode genus and species, Paraspiralatus sakeri, is described from the
      stomach of a wild-caught, female saker falcon in Saudi Arabia. This spirurid
      differs from the nearest genus and species Spiralatus baeri Chabaud, Brygoo &
      Durette, 1963 in the shape of the pseudolabia, shape of the buccal capsule and
      absence of a large cephalic vesicle. In addition, third stage spirurid larvae
      were recovered for the first time from subcutaneous tissues of two houbara
      bustards. These had died in the Rahim Yar Khan Rehabilitation Center (Houbara
      Foundation International, Lahore, Pakistan) in Pakistan and were examined at the
      National Avian Research Center in the United Arab Emirates. The morphology of the
      larvae and host pathology are described. Comparative studies with the adult
      spirurids from the saker falcon showed each to have similar cephalic and
      pharyngeal morphological features to the adults described indicating they are
      probably the same species. Spirurid nematodes of the suborder Spirurina normally
      have an arthropod intermediate host. In view of the host, the site from which the
      larvae were recovered and the fact that this is a rare occurrence, the houbara
      bustard is considered to be a paratenic host.

PMID- 14972035
TI  - Interspecific competition between the nematode-trapping fungus, Duddingtonia
      flagrans, and selected microorganisms and the effect of spore concentration on
      the efficacy of nematode trapping.
AB  - The fungus, Duddingtonia flagrans, is able to trap and kill free-living nematode
      larvae of the cattle parasite Cooperia oncophora when chlamydospores are mixed in
      cattle faeces. Isolates of Bacillus subtilis (two isolates), Pseudomonas spp.
      (three isolates) and single isolates of the fungal genera Alternaria,
      Cladosporium, Fusarium, Trichoderma and Verticillium were isolated from cattle
      faeces and shown to reduce D. flagrans growth on agar plates. When these isolates
      were added to cattle faeces containing D. flagrans and nematode larvae of C.
      oncophora, developing from eggs, none of the isolates reduced nematode mortality
      attributed to D. flagrans. Similarly, the coprophilic fungus Pilobolus kleinii,
      which cannot be cultivated on agar, also failed to suppress the ability of D.
      flagrans to trap and kill developing larvae of C. oncophora. Increasing
      chlamydospore doses of D. flagrans in faecal cultures resulted in higher nematode
      mortality. Thus, no evidence of interspecific or intraspecific competition was
      observed. The consequences of these findings are discussed.

PMID- 14972036
TI  - Detection of inducible nitric oxide synthase in Schistosoma japonicum and S.
      mansoni.
AB  - Schistosoma japonicum and S. mansoni were tested for reactivity with an anti
      inducible nitric oxide (iNOS) antibody and the distribution of iNOS was studied
      by immunofluorescent tests in different stages of the parasites. Reactivity was
      associated with the tegument in both larval schistosomes (sporocysts and
      cercariae) and eggs. With adult worms, the majority of the immunofluorescence was
      predominantly subtegumental in S. japonicum and parenchymal in S. mansoni.
      Fluorescence was also observed in host tissues (snails and mouse liver). In
      Western blots, the enzyme of S. japonicum had an apparent molecular weight of
      about 210 kDa. The possible role of worm and host iNOS in the parasite-host
      interrelation remains to be clarified.

PMID- 14972037
TI  - Metacercarial utilization of a naturally infected single species (Lymnaea
      peregra) snail community by Echinoparyphium recurvatum.
AB  - Utilization of a single-species molluscan community of Lymnaea peregra by
      metacercariae of Echinoparyphium recurvatum over a summer (July-September) period
      in south-east England showed an increase in the mean number of cysts per host
      with host size and time of exposure. Aggregation resulting from host and habitat
      related factors increased with host size and time of exposure. Encystment within
      the host was restricted to the peripheral organs in smaller juvenile snails but
      as snails increased in size, metacercariae were distributed throughout the
      tissues.

PMID- 14972038
TI  - Parasite aggregations in host populations using a reformulated negative binomial
      model.
AB  - The negative binomial distribution model is reformulated and used to demarcate a
      host population at a specific level of infection by defining an attribute
      spanning a range of parasite aggregations. The upper limit of the range specifies
      the boundary for the classification of the host population and provides a
      technique to determine the cumulative probability at any level of parasite
      infection to a high degree of accuracy. This approach also leads to the
      evaluation of the k parameter, i.e. an inverse measure of dispersion of parasite
      aggregation, for each fraction of the host population with a discrete level of
      infection. The basic mathematical premise of the negative binomial function is
      unaltered in developing this reformulation which was applied to data on the
      distribution of the trichostrongylid nematode Heligmosomoides polygyrus in
      populations of the field mouse, Apodemus sylvaticus.

PMID- 14972039
TI  - Surface carbohydrates of Eudiplozoon nipponicum pre- and post-fusion.
AB  - The development of the monogenean Diplozoon (Nordmann, 1832) (Diplozoidae)
      necessitates fusion of two larval stages (diporpae) into one double organism. How
      diporpae find, distinguish and contact each other is unclear, nor is the nature
      of the stimuli responsible for the dedifferentiation of cells and the formation
      of new tissues at the site of somatic fusion. Previous studies have implied a
      role for carbohydrates and glycoproteins in the interactions between helminth
      parasites and their hosts. Hypothetically, glycoconjugates may also be involved
      in the establishment of parasite-parasite associations. Changes in the surface
      saccharide residues during the development of Eudiplozoon nipponicum, a gill
      ectoparasite of carp (Cyprinus carpio) are described. Flat-fixed specimens and
      sections of diporpae, juveniles (just-fused) and adult worms were examined
      following exposure to a panel of 12 FITC-conjugated lectins. All developmental
      stages exhibited a specific surface binding pattern with ten lectins, indicating
      that Man/Glc, GlcNAc, Gal and GalNAc are probably present on their surfaces. No
      reaction was observed with Fuc-specific lectins (UEA-I and LTA). There is
      evidence that parasite development is accompanied by both qualitative and
      quantitative changes in the saccharide pattern distribution. The diporpa sucker
      reacted with nine lectins, excluding BS-II. A very strong binding of PNA, LCA and
      ConA (Gal and Man/Glc-specific lectins) was observed with the papilla glands of
      juvenile worms. The role of glandular secretions in this unique fusion process is
      discussed.

PMID- 14972040
TI  - Faecal egg counts provide a reliable measure of Trichostrongylus tenuis
      intensities in free-living red grouse Lagopus lagopus scoticus.
AB  - The reliability of different egg counting methods for estimating the intensity of
      Trichostrongylus tenuis infections in red grouse, Lagopus lagopus scoticus, was
      investigated in the autumn, when grouse may harbour high parasite intensities.
      Possible limitations to the use of these methods were also examined. Faecal egg
      counts were found to accurately estimate T. tenuis worm intensities, at least up
      to an observed maximum of c. 8000 worms. Two egg counting methods (smear and
      McMaster) gave consistent results, although the exact relationship with worm
      intensity differed according to the method used. Faecal egg counts significantly
      decreased with increasing length of sample storage time, but egg counts were
      reliable for estimating worm intensity for three weeks. The concentration of eggs
      in the caecum was also found to reliably estimate worm intensity. However, egg
      counts from frozen gut samples cannot be used to estimate worm intensities. These
      results conclude that, despite some limitations, faecal and caecum egg counts
      provide useful and reliable ways of measuring T. tenuis intensities in red
      grouse.

PMID- 14972041
TI  - Pallisentis rexus from the Chiang Mai Basin, Thailand: ultrastructural studies on
      egg envelope development and the mechanism of egg expansion.
AB  - Pallisentis rexus Wongkham & Whitfield, 1999 (Eoacanthocephala: Quadrigyridae)
      infects the freshwater snakehead fish, Channa striata, in the Chiang Mai Basin,
      Thailand. All stages of egg development within the body cavity of the female
      parasite were observed, using transmission electron microscopy. Changes in mature
      eggs after contact with water were also investigated. The mature egg has five egg
      envelopes separated from each other by four gaps. The fertilization membrane,
      which is formed first, is pushed centrifugally by other, subsequently formed,
      envelopes and gaps, which produces a final total shell thickness of 8-36 microm
      around the acanthor. The disappearance of the outermost layer and the unpleating
      of an adjacent inner layer causes the expansion of eggs on contact with water.
      The volume of an expanded egg is approximately 27 times that of an unexpanded
      one, but the density of eggs is reduced from a value greater than water to one
      almost equal to water. This is believed to aid the dispersion of eggs.

PMID- 14972042
TI  - Dexamethasone treatment affects skin mucous cell density in Gyrodactylus
      derjavini infected Salmo salar.
AB  - Atlantic salmon, Salmo salar, is normally rather refractive to infection with the
      ectoparasitic monogenean Gyrodactylus derjavini but dexamethasone treatment of
      the host increases the susceptibility. The causative mechanisms were elucidated
      in this work. Groups of Atlantic salmon were treated by intra-peritoneal
      dexamethasone injections and subsequently infected with G. derjavini. It was
      shown that both the infection level and the mucous cell density of caudal and
      pelvic fins were affected by the treatment. Significantly higher mucous cell
      densities were found on infected and treated fish whereas non-infected and
      treated fish showed no significant elevation of cell density. This suggests that
      mucous cell discharge elicited by infection is inhibited by the drug. The
      association with elevated parasite counts in these fish can be explained either
      by decreased anti-parasitic mucus action or by parasite predilection for intact
      mucous cells.

PMID- 14972043
TI  - Echinostoma friedi: the effect of age of adult worms on the infectivity of
      miracidia.
AB  - The effect of ageing of adults of Echinostoma friedi (Trematoda:
      Echinostomatidae) on the infectivity of miracidia yielded was analysed. Miracidia
      were obtained after hatching of eggs obtained from adult worms of E. friedi
      collected weekly during the course of experimental infections in golden hamsters.
      Miracidial infectivity, measured in terms of percentage of infection in Lymnaea
      peregra, was significantly influenced by the age of the adult worms from which
      the miracidia were derived. Infective miracidia only were obtained from adult
      worms in the age range from 4 to 9 weeks post-infection. Infectivity was maximal
      in those miracidia derived from adults collected 8 and 9 weeks post-infection.
      The results suggest that adult worms producing viable eggs require additional
      maturation to be able to yield eggs containing infective miracidia.

PMID- 14972044
TI  - Comparing mark-recapture and constant removal protocols for estimating forager
      population size of the subterranean termite Coptotermes lacteus (Isoptera:
      Rhinotermitidae).
AB  - Forager population sizes of colonies of Coptotermes lacteus(Froggatt) in New
      South Wales were estimated using two methods: mark-recapture and constant
      removal, in two disturbed habitats: a pine plantation and cleared farmland. Mark
      recapture population estimates were unrealistic and unreliable: they could be
      improbably large, over 200 million foragers, and they varied enormously between
      samples for each colony without any pattern. The constant removal population
      estimates could also be unrealistic: they could be negative or quite different
      when calculated using regression and maximum likelihood methods. However, the
      unrealistic results could be predicted reliably, and explained by the lack of re
      contact with the sampling devices (bait stations) - a violation of an assumption
      of the method. This happened more frequently in the plantation than in the
      farmland, probably because of the greater abundance of alternative food sources
      in the plantation. Of the two methods, constant removal provided reasonable
      forager population estimates, relative to direct counts, at least some of the
      time, plus a mechanism by which reliability could be tested, whereas mark
      recapture provided neither. Further refinement and testing of constant removal
      methods are urged to provide a more reliable population estimation technique for
      termites.

PMID- 14972045
TI  - Genetic diversity and insecticide resistance of Myzus persicae (Hemiptera:
      Aphididae) populations from tobacco in Chile: evidence for the existence of a
      single predominant clone.
AB  - The tobacco-feeding race of Myzus persicae (Sulzer), formerly known as M.
      nicotianae Blackman, was introduced into Chile during the last decade. In order
      to evaluate the genetic diversity and insecticide resistance status of Chilean
      tobacco aphid populations, a field survey was conducted in 35 tobacco fields
      covering a 300 km latitudinal survey. The populations sampled were characterized
      using microsatellite markers and morphometric multivariate analysis. Insecticide
      resistance levels were assessed through a microplate esterase assay and the
      mutation status of the kdr gene. All samples collected corresponded to the same
      anholocyclic aphid genotype, and showed morphological variation within the range
      expected for the tobacco-feeding race of M. persicae. Esterase activity showed
      the level and variability expected for an R1 clone lacking mutations in the
      sodium channels (susceptible kdr), thus corresponding to a type slightly
      resistant to organophosphate and carbamate, and susceptible to pyrethroid
      insecticides.

PMID- 14972046
TI  - Host plant age and population development of a cereal aphid, Metopolophium
      dirhodum (Hemiptera: Aphididae).
AB  - The sudden decline following the peak in population abundance of aphids on crops
      of small grain cereals is attributed to the joint effect of natural enemies and
      plant senescence. To distinguish between these causes, a four year experiment was
      established in which the numbers of Metopolophium dirhodum (Walker) infesting
      spring wheat plots sown from April to June at c. 14 day intervals were
      determined. Aphid abundance in replicates sown at successive dates peaked within
      a period of 5-9 days (106-171 day degrees above a base temperature of 0 degrees
      C) although their sowing dates varied by 62-97 days (727-1106 day degrees). At
      the time of the aphid population peaks, plants in the different sowings differed
      in age (11-99 days), developmental stage (stage 15-65 on the Zadoks scale), leaf
      nitrogen content and shoot mass. Maximum abundance of M. dirhodum decreased with
      sowing date because the time available for its population increase was shorter on
      late than early sowings. The abundance of M. dirhodum on spring wheat was similar
      to its abundance on winter wheat. After reaching peak abundance, aphids declined
      in numbers within 3-7 days. The effect of host plant ageing on the M.
      dirhodumdecline thus appeared small. Natural enemies (largely mycoses), and
      timing of alata production may have contributed to the aphid decline.

PMID- 14972047
TI  - A bioassay to evaluate the activity of chemical stimuli from grape berries on the
      oviposition of Lobesia botrana (Lepidoptera: Tortricidae).
AB  - A two-choice bioassay was developed to evaluate the role of host-plant berry
      compounds on the oviposition site acceptance of the generalist moth Lobesia
      botrana (Denis & Shiffermuller). A key feature was the lining of the bioassay
      arena with felt which focused oviposition on the test substrates. Initial
      experiments comparing substrates with different physical features indicated that
      smooth textures and spherical shapes with interstices favour oviposition.
      Artificial oviposition substrates were thus constructed with glass spheres in
      order to test the behavioural activity of grapevine berry extracts. Only polar
      extracts obtained by soaking berries in methanol or water stimulated oviposition
      (more eggs were laid on the extract-treated substrate than on the control
      substrate), whereas more apolar ones obtained with chloroform or hexane had no
      significant effect. The prior removal of epicuticular waxes from grape berries
      before extraction did not enhance the stimulatory activity of the methanol
      extract. The oviposition response to this extract was dose-dependent. It is
      concluded that polar compounds present on grape berries act as oviposition
      stimulants for L. botrana.

PMID- 14972048
TI  - Seedling and adult plant resistance to Sitobion avenae (Hemiptera: Aphididae) in
      Triticum monococcum (Poaceae), an ancestor of wheat.
AB  - Cereal aphids are important pests of wheat, Triticum aestivum L. and Triticum
      durum Desf. Crop resistance is a desirable method for managing cereal aphids in
      central North America, where the dominant crop, spring-sown wheat, has a low
      value per unit area. A diploid ancestor of wheat, Triticum monococcum L., is
      reported to be partially resistant to Sitobion avenae (Fabricius), the most
      damaging cereal aphid in the region. To identify potential sources of resistance,
      42 accessions of T. monococcum and three cultivated wheats were infested with
      aphids, seedlings for six days and adult plants for 21 days. Overall resistance
      was estimated by the biomass loss of foliage and spikes in relation to uninfested
      control plants. Antibiosis was estimated by the gain in biomass of aphids during
      infestation, and tolerance was estimated as a biomass conversion ratio, overall
      resistance divided by antibiosis. A few T. monococcum accessions exhibited
      partial resistance. No relationship was found between seedling and adult plant
      resistance: the former exhibited primarily antibiosis and the latter primarily
      tolerance. Two accessions with antibiosis reduced aphid biomass by 60% compared
      with commercial wheats. Tolerance was correlated with growth potential, and was
      useful only in accessions with high growth potential. Four accessions exhibited
      tolerance levels at least 30% greater than commercial wheats. Highly susceptible
      accessions also were identified, which would be useful for investigating the
      inheritance of antibiosis and tolerance.

PMID- 14972049
TI  - Estimating population density of the Formosan subterranean termite, Coptotermes
      formosanus(Isoptera: Rhinotermitidae) using the effective sampling area of in
      ground monitoring stations.
AB  - The effective sampling area of a monitoring station, alpha, was calculated for
      several Coptotermes formosanus Shiraki colonies in Broward County, Florida, USA.
      A simple mark-recapture protocol provided data on termite station catch within a
      foraging range of a colony. Average recapture probability was 0.005 close to the
      release point (< 5 m) and declined to 0.0008 at a distance of 51 to 60 m. The
      relation between the log % termites recaptured was fitted with log distance, to
      determine P(x), the average proportion of captured termites that started at
      distance x from the release point. The effective sampling area was estimated by
      using P(x) and the equation, alpha 2 pi integral [ x P(x)] dx. Integrating this
      equation, an average estimate alpha that ranged from 0.607 to 14.5 m2 was
      obtained. Factors influencing the variation of alpha among the colonies are
      discussed. The effective sampling area estimated should be taken as a reliable
      estimator that translates subterranean termite catches into termite population
      density.

PMID- 14972050
TI  - Role of modified CDC miniature light-traps as an alternative method for sampling
      adult anophelines (Diptera: Culicidae) in the National Mosquito Surveillance
      Programme in India.
AB  - The efficiency of modified CDC miniature light-traps for sampling adult
      mosquitoes was evaluated in comparison with indoor resting, outdoor resting,
      indoor man-landing and outdoor man-landing collections in the hilly district of
      Koraput, Orissa, India. Overall, light-traps captured 78% of adult mosquitoes
      collected by all methods. Of the 16 anopheline species recorded in the study
      area, light-traps effectively sampled 13, contributing about 72% of the total
      anophelines collected by all methods. Light-traps also caught a large number of
      female Culex vishnui Theobald (96%). As fully-fed mosquitoes were predominant
      (82%) and caught alive, light-traps can be used to catch large numbers of vector
      mosquitoes for studies on vector prevalence, distribution, vector incrimination
      and also for laboratory bioassays. Light-trap and indoor resting collections
      revealed similar seasonal trends in numbers of Anopheles culicifacies Giles, A.
      fluviatilis James, A. jeyporiensis James, A. vagus Doenitz, and A. splendidus
      Koidzumi. Age-structure of the samples did not vary significantly between the two
      methods. Light-traps could be used as an alternative to daytime indoor resting
      collections to monitor the seasonal fluctuations in the abundance and parity
      rates of these species. The light-trap collections correlated with indoor and
      outdoor man-landing collections of A. jeyporiensis and the outdoor man-landing
      collections of A. maculatusTheobald in measuring seasonal trends. Light-trap
      collections can thus be used as a substitute for man-landing collections of A.
      jeyporiensis and A. maculatus.

PMID- 14972051
TI  - Mode of inheritance of the polymorphic esterases in Myzus persicae (Hemiptera:
      Aphididae) in Japan.
AB  - Crossing experiments were conducted with 43 different parental clones of Myzus
      persicae (Sulzer) to clarify the genetic bases of esterase variations detected by
      electrophoresis. A total of 468 F1 clones obtained were analysed for variants at
      six polymorphic esterase loci, including one associated with resistance to
      organophosphorus insecticides (RAE). In addition, the effect of six different
      host plants on the activity of esterases was examined. The inheritance of
      variants at two loci could be explained by two-allele models, and that at three
      other loci by three-allele models, while segregation ratios at the RAE locus
      suggested a cumulative effect of the multiple genes. An interdependent assortment
      was found between two loci. The activity of the esterases detected in the
      alimentary canal was affected by the host plant. By combining the variants at the
      six polymorphic esterase loci with those in body colour, a total of 2592 colour
      esterase forms were distinguishable. Thus esterases could be useful as genetic
      markers to study the genotypic composition and its dynamics of M. persicae
      populations.

PMID- 14972052
TI  - Habitat-related mtDNA polymorphism in the stored-bean pest Callosobruchus
      chinensis (Coleoptera: Bruchidae).
AB  - The genetic diversity of populations of the azuki bean beetle, Callosobruchus
      chinensis (Linnaeus) from natural, pre-harvest and post-harvest sites, was
      investigated to understand population structure and gene flow. A 522-bp fragment
      of the mitochondrial gene COI was sequenced for eight populations of C.
      chinensisfrom Japan, Korea and Taiwan collected from different habitats. Six
      haplotypes were detected, one of which, U1, occurred most frequently and widely.
      The following hypotheses were tested as a cause of the wide distribution of
      haplotype U1; (i) topographical separation (by national boundaries), (ii) host
      plant species, and (iii) habitat type (natural, pre-harvest crop, or post-harvest
      storage). Categorization of collection sites by country or by host species did
      not yield differences in the occurrence of haplotype U1, but habitat type did.
      Populations utilizing cultivated post-harvest hosts that were mass stored were
      highly likely to be the common haplotype, whereas host plants in natural habitats
      away from agriculture were utilized by populations with locally characteristic
      haplotypes. Sampling of commercial beans for quarantine and export purposes
      indicated that gene flow in C. chinensis was largely unidirectional into Japan at
      the present time.

PMID- 14972053
TI  - Maturation feeding and reproductive development in adult pine weevil, Hylobius
      abietis (Coleoptera: Curculionidae).
AB  - Maturation feeding on conifer bark by newly emerged Hylobius abietis(Linnaeus) is
      essential for reproductive development. When feeding occurs on young conifer
      transplants, this weevil causes significant economic damage. Between emergence
      and oviposition however, weevils feed on bark from different sources but of
      unknown nutritional 'quality'. The factors influencing the rate of feeding by
      males and females and female reproductive development were determined in
      laboratory bioassays using two contrasting food sources - the bark on different
      species of seedling conifer and on logs of mature trees. The nutritional
      'quality' of bark was characterized by the concentration of nitrogen, total
      sugars, total polyphenols and resin. Regression models were used to show that
      overall, the rate of feeding on the bark of both seedlings and logs increased
      with weevil size and was negatively related to nitrogen concentration. The
      nitrogen concentration in seedling bark (mean 1.1%) was about three times higher
      than that of logs (mean 0.4%). The rate of reproductive development increased
      with nitrogen intake during feeding and the preoviposition period for weevils
      feeding on seedlings and logs was ~ 13 days and 46 days, respectively. Analysis
      of weevil mortality and of the weight gain of surviving weevils suggests that a
      nitrogen content of around 0.3% may be limiting for H. abietis. The possibility
      that nutritionally adequate food resources may be limiting for H. abietis is
      briefly discussed.

PMID- 14972054
TI  - Survival and development of different life stages of Bactrocera zonata (Diptera:
      Tephritidae) reared at five constant temperatures compared to other fruit fly
      species.

PMID- 14972056
TI  - A life course approach to diet, nutrition and the prevention of chronic diseases.
AB  - OBJECTIVE: To briefly review the current understanding of the aetiology and
      prevention of chronic diseases using a life course approach, demonstrating the
      life-long influences on the development of disease. DESIGN: A computer search of
      the relevant literature was done using Medline-'life cycle' and 'nutrition' and
      reviewing the articles for relevance in addressing the above objective. Articles
      from references dated before 1990 were followed up separately. A subsequent
      search using Clio updated the search and extended it by using 'life cycle',
      'nutrition' and 'noncommunicable disease' (NCD), and 'life course'. Several
      published and unpublished WHO reports were key in developing the background and
      arguments. SETTING: International and national public health and nutrition policy
      development in light of the global epidemic in chronic diseases, and the
      continuing nutrition, demographic and epidemiological transitions happening in an
      increasingly globalized world. RESULTS OF REVIEW: There is a global epidemic of
      increasing obesity, diabetes and other chronic NCDs, especially in developing and
      transitional economies, and in the less affluent within these, and in the
      developed countries. At the same time, there has been an increase in communities
      and households that have coincident under- and over-nutrition. CONCLUSIONS: The
      epidemic will continue to increase and is due to a lifetime of exposures and
      influences. Genetic predisposition plays an unspecified role, and with
      programming during fetal life for adult disease contributing to an unknown
      degree. A global rise in obesity levels is contributing to a particular epidemic
      of type 2 diabetes as well as other NCDs. Prevention will be the most cost
      effective and feasible approach for many countries and should involve three
      mutually reinforcing strategies throughout life, starting in the antenatal
      period.

PMID- 14972057
TI  - Diet, nutrition and the prevention of excess weight gain and obesity.
AB  - OBJECTIVES: To review the evidence on the diet and nutrition causes of obesity
      and to recommend strategies to reduce obesity prevalence. DESIGN: The evidence
      for potential aetiological factors and strategies to reduce obesity prevalence
      was reviewed, and recommendations for public health action, population nutrition
      goals and further research were made. RESULTS: Protective factors against obesity
      were considered to be: regular physical activity (convincing); a high intake of
      dietary non-starch polysaccharides (NSP)/fibre (convincing); supportive home and
      school environments for children (probable); and breastfeeding (probable). Risk
      factors for obesity were considered to be sedentary lifestyles (convincing); a
      high intake of energy-dense, micronutrient-poor foods (convincing); heavy
      marketing of energy-dense foods and fast food outlets (probable); sugar-sweetened
      soft drinks and fruit juices (probable); adverse social and economic conditions
      developed countries, especially in women (probable). A broad range of strategies
      were recommended to reduce obesity prevalence including: influencing the food
      supply to make healthy choices easier; reducing the marketing of energy dense
      foods and beverages to children; influencing urban environments and transport
      systems to promote physical activity; developing community-wide programmes in
      multiple settings; increased communications about healthy eating and physical
      activity; and improved health services to promote breastfeeding and manage
      currently overweight or obese people. CONCLUSIONS: The increasing prevalence of
      obesity is a major health threat in both low- and high income countries.
      Comprehensive programmes will be needed to turn the epidemic around.

PMID- 14972058
TI  - Diet, nutrition and the prevention of type 2 diabetes.
AB  - OBJECTIVES: The overall objective of this study was to evaluate and provide
      evidence and recommendations on current published literature about diet and
      lifestyle in the prevention of type 2 diabetes. DESIGN: Epidemiological and
      experimental studies, focusing on nutritional intervention in the prevention of
      type 2 diabetes are used to make disease-specific recommendations. Long-term
      cohort studies are given the most weight as to strength of evidence available.
      SETTING AND SUBJECTS: Numerous clinical trials and cohort studies in low, middle
      and high income countries are evaluated regarding recommendations for dietary
      prevention of type 2 diabetes. These include, among others, the Finnish Diabetes
      Prevention Study, US Diabetes Prevention Program, Da Qing Study; Pima Indian
      Study; Iowa Women's Health Study; and the study of the US Male Physicians.
      RESULTS: There is convincing evidence for a decreased risk of diabetes in adults
      who are physically active and maintain a normal body mass index (BMI) throughout
      adulthood, and in overweight adults with impaired glucose tolerance who lose
      weight voluntarily. An increased risk for developing type 2 diabetes is
      associated with overweight and obesity; abdominal obesity; physical inactivity;
      and maternal diabetes. It is probable that a high intake of saturated fats and
      intrauterine growth retardation also contribute to an increased risk, while non
      starch polysaccharides are likely to be associated with a decreased risk. From
      existing evidence it is also possible that omega-3 fatty acids, low glycaemic
      index foods and exclusive breastfeeding may play a protective role, and that
      total fat intake and trans fatty acids may contribute to the risk. However,
      insufficient evidence is currently available to provide convincing proof.
      CONCLUSIONS: Based on the strength of available evidence regarding diet and
      lifestyle in the prevention of type 2 diabetes, it is recommended that a normal
      weight status in the lower BMI range (BMI 21-23) and regular physical activity be
      maintained throughout adulthood; abdominal obesity be prevented; and saturated
      fat intake be less than 7% of the total energy intake.

PMID- 14972059
TI  - Diet, nutrition and the prevention of hypertension and cardiovascular diseases.
AB  - Cardiovascular diseases (CVD) are growing contributors to global disease burdens,
      with epidemics of CVD advancing across many regions of the world which are
      experiencing a rapid health transition. Diet and nutrition have been extensively
      investigated as risk factors for major cardiovascular diseases like coronary
      heart disease (CHD) and stroke and are also linked to other cardiovascular risk
      factors like diabetes, high blood pressure and obesity. The interpretation of
      evidence needs to involve a critical appraisal of methodological issues related
      to measurement of exposures, nature of outcome variables, types of research
      design and careful separation of cause, consequence and confounding as the basis
      for observed associations. Adequate evidence is available, from studies conducted
      within and across populations, to link several nutrients, minerals, food groups
      and dietary patterns with an increased or decreased risk of CVD. Dietary fats
      associated with an increased risk of CHD include trans-fats and saturated fats,
      while polyunsaturated fats are known to be protective. Dietary sodium is
      associated with elevation of blood pressure, while dietary potassium lowers the
      risk of hypertension and stroke. Regular frequent intake of fruits and vegetables
      is protective against hypertension, CHD and stroke. Composite diets (such as DASH
      diets, Mediterranean diet, 'prudent' diet) have been demonstrated to reduce the
      risk of hypertension and CHD. Sufficient knowledge exists to recommend
      nutritional interventions, at both population and individual levels, to reduce
      cardiovascular risk. That knowledge should now be translated into policies which
      promote healthy diets and discourage unhealthy diets. This requires coordinated
      action at the level of governments, international organizations, civil society
      and responsible sections of the food industry.

PMID- 14972060
TI  - Diet, nutrition and the prevention of cancer.
AB  - OBJECTIVE: To assess the epidemiological evidence on diet and cancer and make
      public health recommendations. DESIGN: Review of published studies, concentrating
      on recent systematic reviews, meta-analyses and large prospective studies.
      CONCLUSIONS AND RECOMMENDATIONS: Overweight/obesity increases the risk for
      cancers of the oesophagus (adenocarcinoma), colorectum, breast (postmenopausal),
      endometrium and kidney; body weight should be maintained in the body mass index
      range of 18.5-25 kg/m(2), and weight gain in adulthood avoided. Alcohol causes
      cancers of the oral cavity, pharynx, oesophagus and liver, and a small increase
      in the risk for breast cancer; if consumed, alcohol intake should not exceed 2
      units/d. Aflatoxin in foods causes liver cancer, although its importance in the
      absence of hepatitis virus infections is not clear; exposure to aflatoxin in
      foods should be minimised. Chinese-style salted fish increases the risk for
      nasopharyngeal cancer, particularly if eaten during childhood, and should be
      eaten only in moderation. Fruits and vegetables probably reduce the risk for
      cancers of the oral cavity, oesophagus, stomach and colorectum, and diets should
      include at least 400 g/d of total fruits and vegetables. Preserved meat and red
      meat probably increase the risk for colorectal cancer; if eaten, consumption of
      these foods should be moderate. Salt preserved foods and high salt intake
      probably increase the risk for stomach cancer; overall consumption of salt
      preserved foods and salt should be moderate. Very hot drinks and foods probably
      increase the risk for cancers of the oral cavity, pharynx and oesophagus; drinks
      and foods should not be consumed when they are scalding hot. Physical activity,
      the main determinant of energy expenditure, reduces the risk for colorectal
      cancer and probably reduces the risk for breast cancer; regular physical activity
      should be taken.

PMID- 14972061
TI  - Diet, nutrition and the prevention of dental diseases.
AB  - Oral health is related to diet in many ways, for example, nutritional influences
      on craniofacial development, oral cancer and oral infectious diseases. Dental
      diseases impact considerably on self-esteem and quality of life and are expensive
      to treat. The objective of this paper is to review the evidence for an
      association between nutrition, diet and dental diseases and to present dietary
      recommendations for their prevention. Nutrition affects the teeth during
      development and malnutrition may exacerbate periodontal and oral infectious
      diseases. However, the most significant effect of nutrition on teeth is the local
      action of diet in the mouth on the development of dental caries and enamel
      erosion. Dental erosion is increasing and is associated with dietary acids, a
      major source of which is soft drinks. Despite improved trends in levels of dental
      caries in developed countries, dental caries remains prevalent and is increasing
      in some developing countries undergoing nutrition transition. There is convincing
      evidence, collectively from human intervention studies, epidemiological studies,
      animal studies and experimental studies, for an association between the amount
      and frequency of free sugars intake and dental caries. Although other fermentable
      carbohydrates may not be totally blameless, epidemiological studies show that
      consumption of starchy staple foods and fresh fruit are associated with low
      levels of dental caries. Fluoride reduces caries risk but has not eliminated
      dental caries and many countries do not have adequate exposure to fluoride. It is
      important that countries with a low intake of free sugars do not increase intake,
      as the available evidence shows that when free sugars consumption is <15-20 kg/yr
      ( approximately 6-10% energy intake), dental caries is low. For countries with
      high consumption levels it is recommended that national health authorities and
      decision-makers formulate country-specific and community-specific goals for
      reducing the amount of free sugars aiming towards the recommended maximum of no
      more than 10% of energy intake. In addition, the frequency of consumption of
      foods containing free sugars should be limited to a maximum of 4 times per day.
      It is the responsibility of national authorities to ensure implementation of
      feasible fluoride programmes for their country.

PMID- 14972062
TI  - Diet, nutrition and the prevention of osteoporosis.
AB  - OBJECTIVE: To review the evidence on diet and nutrition relating to osteoporosis
      and provide recommendations for preventing osteoporosis, in particular,
      osteopototic fracture. APPROACH: Firstly, to review the definition, diagnosis and
      epidemiology of osteoporosis, to discuss the difficulties in using bone mineral
      density to define osteoporosis risk in a world-wide context and to propose that
      fragility fracture should be considered as the disease endpoint. Secondly, to
      provide an overview of the scientific data, the strengths and weaknesses of the
      evidence and the conceptual difficulties in interpreting studies linking diet,
      nutrition and osteoporosis. The following were considered: calcium, vitamin D,
      phosphorus, magnesium, protein and fluorine. Other potential dietary influences
      on bone health were also discussed, including vitamins, trace elements,
      electrolytes, acid-base balance, phyto-oestrogens, vegetarianism and lactose
      intolerance. CONCLUSIONS: There is insufficient knowledge linking bone mineral
      status, growth rates or bone turnover in children and adolescents to long-term
      benefits in old age for these indices to be used as markers of osteoporotic
      disease risk. For adults, the evidence of a link between intakes of any dietary
      component and fracture risk is not sufficiently secure to make firm
      recommendations, with the exception of calcium and vitamin D. For other aspects
      of the diet, accumulating evidence suggests that current healthy-eating advice to
      decrease sodium intake, to increase potassium intake, and to consume more fresh
      fruits and vegetables is unlikely to be detrimental to bone health and may be
      beneficial.

PMID- 14972063
TI  - The joint WHO/FAO expert consultation on diet, nutrition and the prevention of
      chronic diseases: process, product and policy implications.

PMID- 14972065
TI  - Out of the box.

PMID- 14972066
TI  - The European Nutrition Leadership Programme - 10 years of cultivating future
      leaders in nutrition.

PMID- 14972067
TI  - Under- and overreporting of energy is related to obesity, lifestyle factors and
      food group intakes in Jamaican adults.
AB  - OBJECTIVE: Research in industrialised countries has documented a high prevalence
      of underreported energy intakes associated with characteristics such as obesity.
      This paper examines the prevalence, patterns and impact of energy under- and
      overreporting on diet-obesity relationships in a middle-income developing
      country. DESIGN: A 70-item food-frequency questionnaire was used. Underreporters
      had reported energy intakes <1.35 x basal metabolic rate (BMR), overreporters
      >2.4 x BMR. Multinomial models were used to identify characteristics associated
      with implausible reporting. Intakes were compared across reporting groups to
      assess evidence of bias. Associations between diet and obesity were compared with
      and without adjustment for implausible reporting. SETTING: Spanish Town,
      neighbouring the capital city of Kingston, Jamaica. SUBJECTS: Eight hundred and
      ninety-one Jamaican adults, aged 25-75 years, were randomly recruited. RESULTS:
      More women than men (38.6% vs. 22.5%) underreported, but more men overreported
      energy (23.7% vs. 16.0%). Underreporting was positively associated with obesity,
      special diets, smoking and age; age was inversely associated with overreporting.
      Underreporters estimated lower energy from potentially socially undesirable food
      groups (e.g. snacks) and higher intakes of 'healthy' foods (e.g. fruit) than did
      plausible reporters. For some of these food groups, significant differences in
      intakes among normal-weight versus obese subjects observed among plausible
      reporters were absent when implausible reporters were included. In models of food
      group-obesity associations, adjusting for implausible energy yielded more
      credible results that more closely resembled findings in plausible reporters.
      CONCLUSIONS: Energy under- and overreporting are highly prevalent in Jamaica.
      Adjusting for implausible reporting may help to reduce bias in diet-health
      outcome associations.

PMID- 14972068
TI  - Energy-dense diets are associated with lower diet costs: a community study of
      French adults.
AB  - OBJECTIVE: High consumption of energy-dense foods has been linked to high energy
      intakes and excess weight gain. This study tested the hypothesis that high energy
      density of the total diet is associated with lower diet costs. DESIGN: Dietary
      intakes of 837 French adults, aged 18-76 years, were assessed using a dietary
      history method. Dietary energy density (MJ kg(-1)) was calculated by dividing
      total energy by the edible weight of foods consumed. Daily diet cost ( in day(
      1)) was estimated using mean national food prices for 57 food items. The
      relationship between dietary energy density and diet cost at each level of energy
      intake was examined in a regression model, adjusted for gender and age. RESULTS:
      The more energy-dense refined grains, sweets and fats provided energy at a lower
      cost than did lean meats, vegetables and fruit. Within each quintile of energy
      intake, diets of lower energy density (MJ kg(-1)) were associated with higher
      diet costs ( in day(-1)). CONCLUSION: In this observational study, energy-dense
      diets cost less whereas energy-dilute diets cost more, adjusting for energy
      intakes. The finding that energy-dilute diets are associated with higher diet
      costs has implications for dietary guidelines and current strategies for dietary
      change.

PMID- 14972069
TI  - Determinants of diet quality.
AB  - BACKGROUND: An unbalanced diet is a main risk factor for several chronic
      diseases. This paper identifies groups of individuals with an unbalanced diet
      based on the consumption of nutrients. A characterisation of the groups may help
      to focus efforts aimed at improving the dietary behaviour of the population.
      METHODS: Using nutritional data of 1763 men and 2267 women participating in the
      German Nutrition Survey of 1998, we constructed two indices for diet quality that
      each combines a large amount of nutrients into a single indicator. The impact of
      sociodemographic and lifestyle characteristics on the diet quality indices was
      analysed using multiple regression analyses. RESULTS: The results show a
      considerable variation of diet quality between different groups of individuals.
      High diet quality in terms of the consumption of vitamins, minerals and trace
      elements is positively associated with income, education level, age, energy
      intake, food diversity, sport activity and vegetarianism. On the other hand, a
      low diet quality as indicated by high intakes of e.g. fat, sugar, alcohol and
      sodium can be expected when energy intake is high, for individuals of middle age
      and for pregnant and breast-feeding women. CONCLUSION: The results of this study
      help to identify groups of individuals with preferable and non-preferable diet
      quality. For developing public health strategies, in particular the impact of age
      on diet quality seems to be interesting. The rising diet quality with increasing
      age could reflect a changing health consciousness. It could thus be a challenge
      for health policy to promote a healthy way of living focused especially on young
      individuals.

PMID- 14972070
TI  - Dietary selenium intake by men and women in high and low selenium areas of
      Punjab.
AB  - OBJECTIVE: To determine the selenium intake of adults residing in high and low
      selenium areas of rural Punjab. DESIGN: All food samples consumed by the subjects
      were collected and analysed for selenium content. Based on food intake data and
      selenium content of foods, the selenium intake of the subjects was calculated.
      Hair, fingernails and urine samples from a sub-sample of subjects were collected
      and analysed for selenium. SETTING: Three villages from the selenium-endemic area
      of Nawan Shahr District and two villages from the non-endemic area of Ludhiana
      District, Punjab, India, were covered. SUBJECTS: Forty families from each of the
      two areas, with one adult male and one adult female in the age range of 20-40
      years, were surveyed. Thus a total of 80 men and 80 women constituted the study
      sample. RESULTS: In the selenium-endemic area, the average selenium intake of
      both men and women was more than nine times that in the non-endemic area and
      exceeded the maximum tolerable limit in more than 60% of men. Mean selenium
      content of the hair, nails and urine of both men and women was tens of times
      higher than in the non-endemic area. CONCLUSIONS: High selenium intake in the
      endemic area resulted in high selenium content in the hair, nails and urine of
      men and women. In addition, clinical symptoms of selenium toxicity were also
      observed in some of the subjects. Selenium intake in the non-endemic area was
      marginally below the suggested value. Based on the study results, steps need to
      be taken to educate the public in the endemic area to avoid selenium toxicity.

PMID- 14972071
TI  - Dietary behaviour of German adults differing in levels of sport activity.
AB  - OBJECTIVE: To analyse the dietary behaviour of persons engaging in different
      levels of sport activity. DESIGN: A cross-sectional survey analysis. SETTING: A
      population-based sample of German adults. SUBJECTS: A total of 1756 men and 2254
      women participating in the German National Health Interview and Examination
      Survey and the integrated German Nutrition Survey 1998. RESULTS: Among both
      genders, the median micronutrient intakes of active persons were more preferable
      than those of sedentary persons when German current reference values were used as
      a criterion. The median nutrient densities were also higher in the diet of active
      persons, especially those of vitamin E, calcium, magnesium, and among women also
      those of folate and vitamin C. On average, active persons consumed higher amounts
      of fruit/vegetable juice, drinking water, milk products (including cheese) and
      fruits. Active men additionally consumed higher amounts of vegetables and
      vegetable fat. The contribution of dietary supplements to the total nutrient
      intake was 3%, on average, for active men and women. Compared with sedentary
      persons, this contribution was significantly higher for vitamins, and among men
      also for calcium and magnesium. CONCLUSION: There was no indication of an
      impaired micronutrient intake of active and moderately active persons compared
      with sedentary persons.

PMID- 14972072
TI  - Having lunch at a staff canteen is associated with recommended food habits.
AB  - OBJECTIVE: To describe the characteristics of employees having lunch at staff
      canteens and to examine the association between workplace lunch and recommended
      food habits. DESIGN: A mailed questionnaire including data on lunch pattern, food
      habits, sociodemographic background, work-related factors and body weight.
      Logistic regression models including food habits as dependent variables and lunch
      pattern, sociodemographic factors, work-related factors and body mass index as
      independent variables. SETTING: Helsinki Health Study survey data, collected in
      spring 2001. SUBJECTS: Employees from the City of Helsinki reaching 40, 45, 50,
      55 and 60 years. The data included 2474 women and 591 men; the response rate was
      68%. RESULTS: About half of those with a staff canteen at work had lunch there.
      Those with higher educational level were more likely to have lunch at the staff
      canteen, as also were women with pre-school children and normal-weight men. Those
      having lunch at staff canteens were more likely to follow recommended food
      habits, compared with other subjects. Having lunch at the staff canteen seemed to
      increase the consumption frequency of vegetables and fish. CONCLUSIONS: Having
      lunch at staff canteens is associated with the quality of the diet. To serve a
      cooked meal including vegetables during working time may be an efficient way to
      improve diet among adult employees. More emphasis should be put on increasing the
      possibility for employees to have lunch at staff canteens.

PMID- 14972073
TI  - Consistency of use of plant stanol ester margarine in Finland.
AB  - OBJECTIVE: The aims of this study were to investigate the consistency of use of
      plant stanol ester margarine and to characterise consistent and inconsistent
      users. DESIGN: A cohort of plant stanol ester margarine users was established
      based on 14 national surveys conducted by the National Public Health Institute in
      Finland between 1996 and 1999. A follow-up study questionnaire was developed and
      sent to 1294 users in 2000. SETTING: Subjects who reported using plant stanol
      ester margarine in both the original survey and the follow-up study were
      classified as consistent users, and the rest as inconsistent users. SUBJECTS: The
      study population consisted of 1094 subjects aged 18-87 years, 590 men and 504
      women. RESULTS: There were 357 (33%) consistent and 737 (67%) inconsistent users
      of plant stanol ester margarine in the study population. Consistent users were
      more likely to be men and to have a higher household income than inconsistent
      users. Both consistent and inconsistent users were predominantly middle-aged
      persons with a healthy lifestyle and diet as well as a history of cardiovascular
      disease. Healthfulness was the main factor affecting bread spread choice among
      94% of the consistent users and 59% of the inconsistent users. CONCLUSIONS: The
      use of plant stanol ester margarine is more often inconsistent than consistent.
      There is nevertheless a relatively large subgroup of long-term users of plant
      stanol ester margarine. It is important to examine the health effects especially
      among these regular users.

PMID- 14972074
TI  - Assessment of the nutritional risk of >53-year-old men and women in Taiwan.
AB  - OBJECTIVE: The study was conducted to gain an understanding of the status of
      potential nutrition risks in >53-year-old men and women in Taiwan. METHODS: The
      study employed a validated nutrition-risk screening questionnaire, the Mini
      Nutritional Assessment, to assess the potential risk of undernutrition in the
      elderly population in Taiwan. The questionnaire was translated into the local
      language, Chinese, and was modified slightly based on cultural considerations. It
      was administered to 4440 randomly selected subjects by means of face-to-face
      interviews. The questionnaire included questions on subjective self-evaluations,
      global parameters, simple dietary assessment and some anthropometric
      measurements. RESULTS: Results show that the questionnaire can be used
      effectively as a tool to screen for individuals who are at risk of
      undernutrition. It showed that the proportion of the elderly population at risk
      of nutritional inadequacy is relatively low, but does increase with advanced
      ageing. The proportion of the elderly considered at high risk of undernutrition
      was found to increase with age, ranging from 0.88% for 53-60-year-old subjects to
      1.86% for subjects aged 60-70 years, 3.6% for 70-80-year-olds and 5.3% for >80
      year-old subjects. CONCLUSION: The study showed that a simple questionnaire
      adopted from the Mini Nutritional Assessment can be employed to provide a
      preliminary screening and to identify individuals who are potentially at
      increased risk of nutritional inadequacy in the elderly population in Taiwan.

PMID- 14972075
TI  - Nutrition and lifestyle in relation to bowel movement frequency: a cross
      sectional study of 20630 men and women in EPIC-Oxford.
AB  - OBJECTIVE: To investigate the relationships between nutritional and lifestyle
      factors and bowel movement frequency. DESIGN: Cross-sectional analysis using data
      from a prospective study. Mean numbers of bowel movements were calculated in
      relation to a range of factors. In addition, individuals were categorised
      according to frequency of bowel movements: fewer than 7 per week ('less than
      daily') versus 7 or more per week ('daily'), and odds ratios were calculated from
      logistic regression models. Results for each factor were adjusted for the other
      factors under consideration. SETTING: The European Prospective Investigation into
      Cancer and Nutrition, Oxford cohort (EPIC-Oxford), UK. PARTICIPANTS: In total,
      20630 men and women aged 22-97 years at recruitment. Thirty per cent of the
      subjects were vegetarians or vegans. RESULTS: Women had fewer bowel movements on
      average than men, and were less likely to have daily bowel movements. Mean bowel
      movement frequency was higher in vegetarians (10.5 in men, 9.1 in women) and
      especially in vegans (11.6 in men, 10.5 in women) compared with participants who
      ate meat (9.5 in men, 8.2 in women). There were also significant positive
      associations between bowel movement frequency and body mass index (BMI), intakes
      of dietary fibre and non-alcoholic fluids, for both men and women. Vigorous
      exercise was positively associated with bowel movement frequency in women
      although results for men were less clear. Alcohol intake was positively
      associated with bowel movement frequency in men but not in women. CONCLUSION:
      Being vegetarian and especially vegan is strongly associated with a higher
      frequency of bowel movements. Moreover, having a high intake of dietary fibre and
      fluids and a high BMI are associated with an increase in frequency of bowel
      movements.

PMID- 14972076
TI  - Consumption of foods by young children with diagnosed campylobacter infection - a
      pilot case-control study.
AB  - OBJECTIVE: To determine whether parentally reported habitual intake of specific
      foods differed between children with diagnosed Campylobacter jejuni infection and
      children of a comparison group without diagnosed infection. DESIGN, SETTING AND
      SUBJECTS: Information was collected from the parents or primary caregivers of
      South Australian children aged 1-5 years with diagnosed C. jejuni (cases, n=172)
      and an age- and gender-matched group of uninfected children (controls, n=173).
      Frequency of consumption of 106 food and drink items was determined for the
      preceding two months by food-frequency questionnaire. Four children in the
      control group had recorded diarrhoeal episodes during the assessment period and
      were excluded, so 169 responses were evaluated for this group. Information was
      gathered on possible confounders including socio-economic status. Response
      frequencies were classified into three levels of consumption (rarely, weekly or
      daily) and statistical comparison was made by frequency of consumption of foods
      versus the 'rarely' classification for cases and controls, respectively. RESULTS:
      Frequency of consumption of most foods, including starchy foods and fruits and
      vegetables, did not differ between cases and controls. However, reported
      consumption of eight food items (block and processed cheese (slices and spread),
      salami/fritz (a form of processed sausage), chicken nuggets, pasteurised milk,
      fish (canned or fresh) and hot French fries) was significantly higher by
      controls. CONCLUSIONS: The hypothesis that reported consumption of starchy foods
      was lower by cases than by controls was not supported by the data. However,
      consumption of some processed and unprocessed foods was higher by controls. Some
      of these foods have established bactericidal actions in vitro that may indicate a
      possible mechanism for this apparent protection.

PMID- 14972077
TI  - Reliability and validity of a food-frequency questionnaire for Chinese
      postmenopausal women.
AB  - OBJECTIVES: (1). To determine the reliability and validity of a food-frequency
      questionnaire (FFQ) for use in epidemiological research in postmenopausal women;
      and (2). to compare the volume estimation (VE) and weight estimation (WE) method
      of administration of this questionnaire. DESIGN: An initial list of foods was
      derived and modified after pre-testing in 22 subjects. Test-retest reliability
      was assessed in 21 subjects who had repeat administrations of the questionnaire
      14 days apart (FFQ1, FFQ2). The validity of the FFQ was assessed by comparing
      nutrient intakes with those from a 4-day food record. SETTING: Chengdu, People's
      Republic of China. SUBJECTS: Twenty-two postmenopausal women (50-70 years) were
      recruited from The Second University Hospital, West China University of Medical
      Sciences, Chengdu and participated in the pre-test. Another 21 women (50-70
      years) were randomly selected from the general population of all five districts
      of Chengdu and participated in the reliability and validity sub-studies. RESULTS:
      Energy, protein, carbohydrate, magnesium and sodium intakes in this sample were
      less than the Recommended Dietary Allowances (RDAs) for 45-70-year-old women in
      China. Intake of non-cooking fat was higher than the Chinese RDA. Pearson
      correlation coefficients and intra-class correlation coefficients (ICCs) for
      reliability of the VE FFQ ranged from 0.51 to 0.85 and from 0.51 to 0.81,
      respectively; for the WE FFQ, they ranged from 0.22 to 0.86 and from 0.21 to
      0.81. Correlation coefficients and ICCs for validity of the WE FFQ ranged from
      0.36 to 0.69 and from 0.34 to 0.57, respectively; corresponding values for the VE
      FFQ were -0.30 to 0.65 and -0.14 to 0.65. CONCLUSIONS: Both the VE and WE FFQs
      were reliable and valid except for sodium intake. The VE FFQ provided more valid
      estimates of nutrient intakes than did the WE FFQ.

PMID- 14972078
TI  - Do we still believe in the dopamine hypothesis? New data bring new evidence.
AB  - Schizophrenia is characterized by positive symptoms, negative symptoms and
      cognitive impairment. The dopamine hypothesis of schizophrenia postulates that an
      excess of dopamine subcortically is associated with the positive symptoms. At the
      same time, the negative and cognitive symptoms of schizophrenia are thought to
      arise from a deficit of dopamine in the cortex. Evidence for the co-existence of
      subcortical dopamine excess and cortical dopamine deficit in the schizophrenic
      brain is presented. Neuroreceptor-imaging techniques, such as SPECT and PET, have
      been used to provide that evidence. After amphetamine challenge (to stimulate
      dopamine release), dopamine transmission was substantially increased in the
      brains of schizophrenic subjects compared with healthy controls. In addition,
      amphetamine challenge was associated with an increase in positive symptoms of
      schizophrenia. Furthermore, acute dopamine depletion studies indicated that there
      was an increased occupancy of D2 receptors by dopamine at baseline in
      schizophrenia in comparison with healthy controls. This is consistent with the
      notion of hyperstimulation of D2 receptors in schizophrenia. In the cortex,
      dopamine type-1 (D1) receptors were found to be up-regulated in patients with
      schizophrenia compared to controls; in the dorsolateral prefrontal cortex, a
      brain region involved in working memory, this increase correlated with a poor
      performance on the n-back task. The up-regulation of D1 receptors may represent a
      compensatory effect of the dopamine deficit in the cortex. These findings provide
      evidence for a corticalsubcortical imbalance in the schizophrenic brain.

PMID- 14972079
TI  - Pathways to schizophrenia: the impact of environmental factors.
AB  - Schizophrenia is an aetiologically complex disorder arising from the interaction
      of a range of factors acting at various stages of life. Schizophrenic individuals
      inherit genes that cause structural brain deviations which may be compounded by
      early environmental insults. As a result some pre-schizophrenic children exhibit
      subtle developmental delays, cognitive problems, or poor interpersonal
      relationships. They are susceptible to dysregulation of dopamine, the final
      pathway leading to the onset of a psychotic illness. Dopamine dysregulation may
      arise through a process of sensitization, which, in animals, can be caused by
      repeated administration of dopamine-releasing drugs. It is clear that the same
      process occurs in humans, and that some individuals are particularly sensitive to
      the effects of such drugs for either genetic reasons or through early
      environmental damage. Stress has also been shown to induce dopamine release in
      animal studies, and epidemiological studies have demonstrated that social
      stresses can precipitate schizophrenia. Thus, stresses, such as drug use and
      social adversity, in adolescence or early adult life may propel the
      neurodevelopmentally impaired individual over a threshold into frank psychosis.

PMID- 14972080
TI  - Amisulpride a selective dopamine antagonist and atypical antipsychotic: results
      of a meta-analysis of randomized controlled trials.
AB  - The pharmacological profiles of the atypical antipsychotics, clozapine,
      olanzapine, quetiapine and risperidone, all show a combined serotonin (5-HT2) and
      dopamine type-2 (D2) receptor antagonism. Amisulpride, a highly selective
      dopamine D2/D3 receptor antagonist that binds preferentially to receptors in the
      mesolimbic system, is also an 'atypical' antipsychotic despite having a different
      receptor-affinity profile. A meta-analysis of 18 clinical trials was undertaken
      to compare the efficacy and safety of amisulpride with conventional
      antipsychotics. The improvement in mental state was assessed using the Brief
      Psychiatric Rating Scale (BPRS) or the Scale for the Assessment of Negative
      Symptoms (SANS). In a pooled analysis of 10 studies of acutely ill patients,
      amisulpride was significantly more effective than conventional neuroleptics with
      regard to improvement of global symptoms. Amisulpride is, to date, the only
      atypical antipsychotic for which several studies on patients suffering
      predominantly from negative symptoms have been published. In four such studies,
      amisulpride was significantly superior to placebo. Three small studies with
      conventional neuroleptics as a comparator showed only a trend in favour of
      amisulpride in this regard. Amisulpride was associated with fewer extrapyramidal
      side-effects and fewer drop-outs due to adverse events than conventional
      neuroleptics. These results clearly show that amisulpride is an 'atypical'
      antipsychotic, and they cast some doubt on the notion that combined 5-HT2-D2
      antagonism is the only reason for the high efficacy against negative symptoms and
      fewer extrapyramidal side-effects.

PMID- 14972081
TI  - How do we choose between atypical antipsychotics? The advantages of amisulpride.
AB  - Clinician choice of an atypical antipsychotic may depend on a number of factors
      such as perceived efficacy, tolerability and cost. It is also important that the
      choice of treatment takes into consideration the previous response to treatment,
      experience of side-effects and personal clinical characteristics. The receptor
      affinity profiles of the atypical antipsychotics differ; with the exception of
      amisulpride, a selective D2/D3 antagonist, all the atypical antipsychotics
      exhibit a greater affinity for the serotonin-2A receptors than dopamine
      receptors. However, there is no evidence that the variation in receptor
      affinities is relevant to efficacy. Indeed, the crucial factor may be fast
      dissociation from low affinity for the D2 receptor. Tolerability also varies
      between the atypical antipsychotics and the side-effect profile may be related to
      the receptor-affinity profile of the individual drugs. Extrapyramidal side
      effects are generally less of a problem with most atypical drugs than with
      conventional drugs, but weight gain, loss of glycaemic control, sedation and
      hyperprolactinaemia remain problematic in some patients. Amisulpride is effective
      for the treatment of both positive and negative symptoms, and is well tolerated
      with regard to weight gain, glucose tolerance and sedation. In two clinical
      trials, the AMIRIS and SOLIANOL studies, amisulpride demonstrated clear
      advantages over some other atypical antipsychotics with respect to negative
      symptoms, depressive symptoms and weight gain.

PMID- 14972082
TI  - Primary aldosteronism: a needle in a haystack or a yellow cab on Fifth Avenue?

PMID- 14972083
TI  - Clinical trials report. Food fight: diet and genomics.

PMID- 14972084
TI  - Pharmacogenetics of antihypertensive drug response.
AB  - Pharmacogenetics is a discipline of molecular medicine that investigates the
      genetic basis of individual variation of drug responses. Before the era of the
      human genome project and the subsequent progress in genomic research, this field
      was primarily restricted to the investigation of the genetics of drug
      metabolizing enzymes as they account for individual differences in
      pharmacokinetics and tolerability of drugs. In the current genomic era,
      pharmacogenetic research is applied to all fields of drug treatment in clinical
      medicine, including hypertension research. In contrast to the traditional
      approach, however, the influence of individual genetic variation on the efficacy
      of a drug (ie, the pharmacodynamic response) is the major focus of
      pharmacogenetic research and its clinical applicability. Therefore, the
      identification of individual genetic variation influencing the blood pressure
      lowering effect of an antihypertensive compound and the implementation of this
      knowledge into clinical practice is the major goal of pharmacogenetic research in
      the field of hypertension. In this article, some important, recent research work
      and progress on the pharmacogenetics of antihypertensive drug responses are
      reviewed and evaluated.

PMID- 14972085
TI  - Genetics of vasopressin receptors.
AB  - Membrane receptors that couple to guanine nucleotide binding protein (GPCRs)
      represent one of the largest families of proteins in the genome. Because of their
      universal distribution and multiple actions, genetic variations of GPCRs are
      associated with various human diseases. For instance, the clinical phenotype of
      congenital nephrogenic diabetes insipidus has been linked to more than 155 loss
      of-function putative mutations of the arginine vasopressin (AVP) V(2) receptor,
      which span each and every segment of this seven-transmembrane domain receptor.
      These mutant receptors, which are mostly trapped in the endoplasmic reticulum,
      can be rescued by membrane-permeant nonpeptidic AVP receptor antagonists. An
      overexpression of V(1)-vascular and V(3)-pituitary AVP receptors has been
      observed in some endocrine tumors. The single nucleotide polymorphism of AVP
      receptors in the context of complex genetic traits is currently being
      investigated, and preliminary findings have been reported in arterial
      hypertension and autism.

PMID- 14972086
TI  - Antioxidant vitamins and blood pressure.
AB  - Synthesis of free radicals might play a role in the cellular process of
      atherosclerosis. This process can be stopped by antioxidants such as beta
      carotene, vitamin C, or vitamin E, which will inactivate the effects of free
      radicals. Although antioxidant vitamins have not been proven to prevent
      cardiovascular diseases through the modulation of lipid peroxidation, it has been
      suggested that peroxidation might be a pathway to such prevention, mediated
      through the effects of antioxidants on blood pressure (BP) and arterial
      stiffness. Several observational epidemiologic studies and some clinical trials
      have suggested an inverse association between dietary intake of fruits and
      vegetables, and BP. An inverse link between serum levels of vitamin C and BP has
      also been determined in observational epidemiologic settings. Some relations
      between other antioxidant vitamins (retinol and beta-carotene) and BP are
      reported; they confer the same inverse association. However, results from
      clinical trials testing the effect of a single, or a combination of antioxidants
      at high pharmacologic doses have revealed inconsistent BP findings. So far, no
      evidence confirms that oral antioxidant supplementation is effective in
      preventing or treating high BP. Additional large studies should be conducted to
      determine the effect on BP of antioxidant supplementation at nutritional doses.

PMID- 14972087
TI  - Potassium in hypertension.
AB  - Potassium is the most important ion in the living cell, affecting almost every
      cellular function. Numerous clinical and epidemiologic studies support the
      knowledge that potassium is a fundamental factor in blood pressure regulation.
      The role of potassium in blood pressure regulation is reviewed in this article,
      focusing on its impact on the vascular vessel and the kidney, which are tissues
      strongly affected by potassium balance. The role of potassium on nitric oxide
      synthesis and superoxide formation is analyzed. Finally, the study of cell
      potassium as a marker for hypertension is discussed.

PMID- 14972088
TI  - Genes for left ventricular hypertrophy.
AB  - Left ventricular (LV) hypertrophy is very common, particularly among
      hypertensives. The presence of LV hypertrophy profoundly affects morbidity and
      mortality from cardiovascular diseases and stroke, and is now recognized as the
      most important predictor of chronic heart failure. Hypertension, obesity, and
      diabetes are important determinants of LV hypertrophy, but they fail to identify
      many individuals with the condition, suggesting that other factors, likely
      genetic in origin, play a role. Although much research has been undertaken to
      understand the causes of hypertrophy and the medical treatments that can lead to
      its regression, much remains unknown about its genetic basis. LV hypertrophy is
      considered a complex genetic disease, likely representing an interaction of
      several genes with the environment. The heritability of LV mass, measured as a
      quantitative trait, falls between 0.3 and 0.7 in different populations,
      suggesting it has a familial component. Genes encoding proteins involved in LV
      structure, as well as genes encoding cell signal transduction, hormones, growth
      factors, calcium homeostasis, substrate metabolism, and blood pressure are likely
      candidates for the development of common forms of LV hypertrophy. An overview of
      the pathophysiology of LV hypertrophy and dysfunction is provided, in addition to
      evidence of the genetic basis for LV hypertrophy in humans and animal models.

PMID- 14972090
TI  - Clinical trials report. CHARM-Overall Programme.

PMID- 14972089
TI  - Clinical trials report. The sweet secret of dark chocolate.

PMID- 14972091
TI  - Clinical trials report. CHARM-Alternative Trial.

PMID- 14972092
TI  - Clinical trials report. CHARM-Added Trial.

PMID- 14972093
TI  - Clinical trials report. CHARM-Preserved Trial.

PMID- 14972094
TI  - Is endothelial progenitor cell dysfunction involved in altered angiogenic
      processes in patients with hypertension?
AB  - Hypertension represents one of the most frequent modifiable risk factors for
      cardiovascular disease (CVD). Despite the arrival of novel antihypertensive drugs
      and progress in primary prevention and screening, the improvement of blood
      pressure control does not similarly reduce the incidence of end-organ damage
      associated with hypertension. Recently, the concept of reduced angiogenesis as a
      new CVD risk factor has gained the interest of an increasing number of
      investigators in the field. Indeed, pharmacologic and stem cell-based strategies
      aimed to induce angiogenesis seem to improve the course of ischemic vascular
      disease. However, few to no reports have studied the possible therapeutic
      potential of angiogenesis in essential hypertension. In this review, we discuss
      the potential involvement of endothelial progenitor cells in modulating
      angiogenesis and their putative therapeutic role in improving capillary
      rarefaction and arterial stiffness in essential hypertensive patients.

PMID- 14972095
TI  - Adrenomedullin in vascular diseases.
AB  - A novel vasodilator, adrenomedullin (AM), which acts as an autocrine/paracrine
      factor in cardiovascular system, has antiproliferative and antimigrative effects.
      AM gene transfer prevents the development of cuff-induced vascular injury.
      Moreover, AM knockout mice exhibited an increase in angiotensin (Ang) II/salt
      loading-induced coronary arterial lesion, hypoxia-induced pulmonary vascular
      damage, and cuff-induced vascular injury associated with enhancement in reactive
      oxygen species (ROS) generation. In addition, AM expression was stimulated by
      ROS, and AM directly inhibits oxidative stress so that AM might be a negative
      feedback substance against ROS-induced organ damages. In addition, AM increases
      nitric oxide and ameliorates insulin resistance, leading to oxidative stress.
      Consequently, endogenous AM might compensatively inhibit the development of
      vascular diseases at least partly through an antioxidative effect.

PMID- 14972096
TI  - Mechanisms for early microvascular injury in obesity and type II diabetes.
AB  - Obesity in the absence of hyperglycemia carries a low risk for microvascular
      disease compared with type II diabetes. The occurrence of hyperglycemia seems to
      be an important, if not the most important, distinction between obesity and
      obesity plus diabetes mellitus for microvascular disease. In vitro and in vivo
      human and animal studies of the early microvascular consequences of hyperglycemia
      indicate an immediate detrimental suppression of vasodilatory microvascular
      mechanisms that might be even worse with pre-existing obesity. The overall
      concept emerging from a very large research base is that hyperglycemia activates
      protein kinase C, increases oxidant formation, elevates constrictor prostanoid
      species to the detriment of beneficial prostanoids, and suppresses flow-mediated
      regulation with the nitric oxide generated by endothelial cells. The end result
      is decreased blood flow and loss of microvascular reactivity to endothelial
      dependent vasodilatory stimuli that persists for 3 to 6 hours.

PMID- 14972097
TI  - Metabolic syndrome X: an inflammatory condition?
AB  - Obesity, atherosclerosis, insulin resistance and hyperinsulinemia,
      hyperlipidemia, essential hypertension, type 2 diabetes mellitus, and coronary
      heart disease (CHD) are the components of metabolic syndrome X and are associated
      with elevated plasma levels of C-reactive protein, interleukin-6, and tumor
      necrosis factor-alpha, which are markers of inflammation. This suggests that
      metabolic syndrome X is a low-grade, systemic, inflammatory condition. Hence,
      instituting anti-inflammatory measures might be beneficial in preventing or
      halting the progress of metabolic syndrome X in high-risk populations.

PMID- 14972098
TI  - Towards an embryocentric world: the current and potential uses of embryo
      technologies in dairy production.
AB  - Structural features of the dairy industry make it well situated to use embryo
      technologies as tools for enhancing the genetic merit of dairy cattle and
      improving fertility. Technologies dependent upon embryo transfer have the
      potential to increase the efficiency of quantitative genetic selection as well as
      marker-assisted selection, simplify cross-breeding and germplasm conservation
      procedures and allow incorporation of transgenes into dairy cattle. In addition,
      embryo technologies may prove useful in improving fertility in infertile
      populations of lactating cows. The realisation of the promise of embryo
      technologies has been constrained by suboptimal efficiency in the production of
      embryos, alterations in embryonic and fetal survival and development associated
      with in vitro embryo production and cloning, as well as other technical and
      societal concerns. Solutions to many of these constraints are possible and the
      use of embryo technologies in both nucleus and commercial herds is likely to
      increase. Eventually, embryo transfer may compete with artificial insemination as
      a dominant method for establishing pregnancies in dairy cattle.

PMID- 14972099
TI  - Developments in in vitro technologies for swine embryo production.
AB  - Several modifications have been made to in vitro production (IVP) systems to
      allow more efficient production of viable porcine embryos. Although in vitro
      production of pig embryos has been studied for over 30 years, the overall
      blastocyst production rate remains low. The low blastocyst rate is due to several
      factors, including polyspermic oocyte penetration, low rate of male pronucleus
      formation and less than optimal in vitro culture systems. These conditions are
      all inherent problems in porcine IVP and many of the mechanisms involved remain
      unknown. Considerable research has examined culture medium and the techniques
      used during the various stages of in vitro production. However, changes to the
      physical culture system used during IVF have remained unchanged until recently.
      The present paper will summarise selected developments in fertilisation and
      embryo culture media composition and focus on the development of modified
      equipment to improve the conditions used during the IVP of porcine oocytes and
      embryos.

PMID- 14972100
TI  - Development of national animal genetic resource programs.
AB  - Globally, animal genetic resources are contracting due to economic forces. As a
      result, during the 1990s there was a dramatic increase in national animal genetic
      resource activities. Many national programmes were initiated and the Food and
      Agriculture Organisation of the United Nations played a prominent role in
      coalescing national actions. Nationally, programmes have been initiated that
      comprise of in situ, ex situ and information-exchange efforts. A critical element
      to national conservation efforts is the development of cryopreserved collections
      of germplasm. Several countries have initiated substantial multispecies
      collections of cryopreserved germplasm. The selection of animals within breeds of
      interest is an important consideration in building cryopreserved collections.
      Animal selection should be based on a lack of genetic relationship, with
      sufficient numbers of animals to ensure the capture of rare alleles. Major issues
      facing repository development and genetic conservation are: (1) that all breeds
      are in need of genetic diversity management; (2) a better understanding of in
      situ breed population dynamics is needed; and (3) the concept that repository
      collections can be used by a broad range of clientele across time as well as
      during emergency situations.

PMID- 14972101
TI  - Which reproductive technologies are most relevant to studying, managing and
      conserving wildlife?
AB  - The advent of in vitro fertilisation (IVF) and embryo transfer in the 1970s led
      to speculation about the potential value of these and other 'reproductive
      technologies' to conserving endangered species. So far, and for the most part,
      assisted breeding techniques that are routine in domesticated species are not
      easily adapted to wildlife. Species differences in reproductive form
      (anatomy/morphology) and function (mechanisms regulating reproductive success)
      limit the practical applicability for offspring production. Thus, the limiting
      factor is the lack of basic knowledge about thousands of unstudied species, the
      foundation that is essential to allowing reproduction to be enhanced and/or
      controlled. There now is excellent evidence that reproductive technologies are
      most useful as tools for studying how different species reproduce, especially
      defining novel and unique mechanisms. The present paper reviews the status and
      relevance of various reproductive technologies that are useful or have potential
      for wildlife. Modern examples of progress are provided indicating how these tools
      are being used to understand ways that wildlife species reproduce and, in some
      cases, how such knowledge has been used for successful assisted breeding,
      improved management and conservation.

PMID- 14972102
TI  - An overview of genomics research and its impact on livestock reproduction.
AB  - The amount of information currently available about the genomes of many livestock
      species, especially cattle and pigs, has increased dramatically in the past few
      years and the rate of its accumulation will continue to increase. A large number
      of scientific 'tools' is currently available for research aimed at understanding
      biological processes important to livestock production. These resources are being
      used to understand biological processes regulating reproduction, body composition
      and immune function in all livestock species. This research will create many
      opportunities to develop new tools for the improvement of livestock production.
      The best commercial application of genomics is in conjunction with reproductive
      enhancing technologies, such as artificial insemination, embryo transfer and
      cloning.

PMID- 14972103
TI  - Gene transcription and regulation of oocyte maturation.
AB  - The developmental potential of an embryo is dependent on the developmental
      potential of the oocyte from which it originates. The process of oocyte
      maturation is critical for the efficient application of biotechnologies such as
      in vitro embryo production and mammalian cloning. However, the overall efficiency
      of in vitro maturation remains low because oocytes matured in vitro have a lower
      developmental competence than oocytes matured in vivo. Furthermore, oocytes that
      have been exposed to gonadotropins have greater developmental competence than
      oocytes matured in the absence of gonadotropins. By understanding the molecular
      mechanisms underlying gonadotropin-induced maturation, improvement in oocyte
      maturation technologies may be expected as procedures to manipulate specific
      factors involved in signalling for resumption of meiosis are identified. The
      present review will focus on transcriptional mechanisms underlying the maturation
      of mammalian oocytes in vitro, as well as on the acquisition of oocyte
      developmental competence. In addition, a working model for the transcriptional
      control of mammalian oocyte maturation is proposed.

PMID- 14972104
TI  - Oocyte proteomics: localisation of mouse zona pellucida protein 3 to the plasma
      membrane of ovulated mouse eggs.
AB  - In order to gain a deeper understanding of the molecular underpinnings of sperm
      egg interaction and early development, we have used two-dimensional (2D)
      electrophoresis, avidin blotting and tandem mass spectrometry to identify, clone
      and characterise abundant molecules from the mouse egg proteome. Two-dimensional
      avidin blots of biotinylated zona-free eggs revealed an abundant approximately 75
      kDa surface-labelled heterogeneous protein possessing a staining pattern similar
      to that of the zona pellucida glycoprotein, mouse ZP3 (mZP3). In light of this
      observation, we investigated whether mZP3 specifically localises to the plasma
      membrane of mature eggs. Zona pellucidae of immature mouse oocytes and mature
      eggs were removed using acid Tyrode's solution, chymotrypsin or mechanical
      shearing. Indirect immunofluorescence using the mZP3 monoclonal antibody (mAb) IE
      10 demonstrated strong continuous staining over the entire surface of immature
      oocytes and weak microvillar staining on ovulated eggs, regardless of the method
      of zona removal. Interestingly, in mature eggs, increased fluorescence intensity
      was observed following artificial activation and fertilisation, whereas little to
      no fluorescence was observed in degenerated eggs. The surface localisation of ZP3
      on mature eggs was supported by the finding that the IE-10 mAb immunoprecipitated
      an approximate 75-kDa protein from lysates of biotinylated zona-free eggs. To
      further investigate the specificity of the localisation of mZP3 to the oolemma,
      indirect immunofluorescence was performed using the IE-10 mAb on both CV-1 and
      CHO cells transfected with full-length recombinant mZP3 (re-mZP3). Plasma
      membrane targeting of the expressed re-mZP3 protein was observed in both cell
      lines. The membrane association of re-mZP3 was confirmed by the finding that
      biotinylated re-mZP3 (approximately 75 kDa) is immunoprecipitated from the
      hydrophobic phase of Triton X-114 extracts of transfected cells following phase
      partitioning. Immunoprecipitation assays also demonstrated that surface re-mZP3
      was released from transfected CV-1 in a time-dependent manner. These results
      demonstrate that ZP3 is specifically associated with the surface of mature eggs
      and its subsequent release from the cell surface may represent one mechanism by
      which ZP3 is secreted. Furthermore, the increase in ZP3 surface expression
      following fertilisation suggests that ZP3 may have a functional role during sperm
      oolemma binding and fusion. These results also validate the usefulness of using
      the 2D proteomic approach to identify and characterise egg-surface proteins.

PMID- 14972105
TI  - Embryogenomics of pre-implantation mammalian development: current status.
AB  - Pre-implantation development is marked by many critical molecular events,
      including the maternal to zygotic transition and the first differentiation of
      cells. Understanding such events is important, for both basic reproductive
      biology and practical applications, including regenerative medicine and livestock
      production. Scarcity of materials has hampered the progress of the field, but
      systematic genomics approaches are beginning to be applied to the study of pre
      implantation development, resulting in unprecedented amounts of data about the
      pre-implantation process. The first step in embryogenomics is to collect and
      sequence cDNAs (expressed sequence tags (ESTs)) for genes that are expressed and
      function in these early embryos. Mouse work is the most advanced, with 140 111
      ESTs derived from all stages of pre-implantation development currently available
      in the public sequence database. For other mammals, at present only approximately
      1000 ESTs can be found in the public database, but efforts by several groups are
      generating cDNA libraries and ESTs. In the present review, the current status of
      the implementation of these investigative tools for mammalian pre-implantation
      embryos is discussed.

PMID- 14972106
TI  - Serial analysis of gene expression (SAGE) during porcine embryo development.
AB  - Functional genomics provides a powerful means for delving into the molecular
      mechanisms involved in pre-implantation development of porcine embryos. High
      rates of embryonic mortality (30%), following either natural mating or artificial
      insemination, emphasise the need to improve the efficiency of reproduction in the
      pig. The poor success rate of live offspring from in vitro-manipulated pig
      embryos also hampers efforts to generate transgenic animals for biotechnology
      applications. Previous analysis of differential gene expression has demonstrated
      stage-specific gene expression for in vivo-derived embryos and altered gene
      expression for in vitro-derived embryos. However, the methods used to date
      examine relatively few genes simultaneously and, thus, provide an incomplete
      glimpse of the physiological role of these genes during embryogenesis. The
      present review will focus on two aspects of applying functional genomics research
      strategies for analysing the expression of genes during elongation of pig embryos
      between gestational day (D) 11 and D12. First, we compare and contrast current
      methodologies that are being used for gene discovery and expression analysis
      during pig embryo development. Second, we establish a paradigm for applying
      serial analysis of gene expression as a functional genomics tool to obtain
      preliminary information essential for discovering the physiological mechanisms by
      which distinct embryonic phenotypes are derived.

PMID- 14972107
TI  - Biosecurity issues associated with current and emerging embryo technologies.
AB  - A variety of procedures associated with in vivo and in vitro embryo production,
      as well as cloning and transgenics, are in current use by both researchers and
      practitioners. Biohazards associated with these procedures could influence
      clinical proficiency and the outcome of basic research or result in unusual
      distribution of pathogens in populations of animals. By their nature, embryo
      technologies are vulnerable to contamination from numerous sources. Although
      pathogens can originate in the physical environments in which embryo technologies
      are applied, they are more likely to be introduced via animals or materials of
      animal origin. However, it is important to note that both the occurrence and
      consequences of contamination are heavily influenced by environmental
      circumstances. This paper represents a philosophical description of biohazards
      associated with three generations of embryo technologies using the cow as a model
      species. Emphasis is placed on sources of contamination, current or suggested
      preventive actions and the issue of environmental changes as they relate to the
      emergence of biohazards and the implementation of biosecurity measures. Some
      specific pathogens are discussed for illustration. In addition, details of the
      risks associated with introducing bovine viral diarrhoea virus in each of three
      generations of embryo technologies are described.

PMID- 14972108
TI  - Biosecurity strategies for conserving valuable livestock genetic resources.
AB  - The foot and mouth disease (FMD) epidemic in the UK in 2001 highlighted the
      threat of infectious diseases to rare and valuable livestock and stimulated a
      renewed interest in biosecurity and conservation. However, not all diseases
      resemble FMD: their transmission routes and pathological effects vary greatly, so
      biosecurity strategies must take this into account. Realism is also needed as to
      which diseases to exclude and which will have to be tolerated. The aim should be
      to minimise disease generally and to exclude those diseases that threaten the
      existence of livestock or preclude their national or international movement.
      Achieving this requires a team effort, bearing in mind the livestock species
      involved, the farming system ('open' or 'closed') and the premises. Effective
      biosecurity demands that practically every aspect of farm life is controlled,
      including movements of people, vehicles, equipment, food, manure, animal
      carcasses and wildlife. Above all, biosecurity strategies must cover the disease
      risks associated with moving the livestock themselves and this will require
      quarantine if adult or juvenile animals are imported into the herd or flock. The
      present paper emphasises the important role that reproductive technologies, such
      as artificial insemination and embryo transfer, can have in biosecurity
      strategies because they offer much safer ways for getting new genetic materials
      into herds/flocks than bringing in live animals. Embryo transfer is especially
      safe when the sanitary protocols promoted by the International Embryo Transfer
      Society and advocated by the Office International des Epizooties (the 'World
      Organisation for Animal Health') are used. Embryo transfer can also allow the
      full genetic complement to be salvaged from infected animals. Cryobanking of
      genetic materials, especially embryos, is another valuable biosecurity strategy
      because it enables their storage for conservation in the face of contingencies,
      such as epidemic disease and other catastrophes.

PMID- 14972109
TI  - Integrating new technologies with embryology and animal production.
AB  - The present review describes a range of selected farm animal embryo technologies
      used in embryological research and applied in animal breeding and production.
      Some of the techniques are driven by the breeder's wish to obtain animals with
      higher breeding values, whereas others are primarily driven by the curiosity of
      researchers. The interaction between basic research and practical application in
      these areas is still a characteristic feature for people who contribute to the
      International Embryo Transfer Society (IETS) and has been an advantage for both
      researchers and breeders. One example of such an interaction is that detailed
      structural analyses have described quality differences between embryos of various
      origins and, following embryo transfer, the pregnancy results have confirmed the
      correlation between morphology and viability. Another example is that polymerase
      chain reaction technology has allowed detection of Y-specific sequences in male
      embryos and has become a tool in animal production today. Data from domestic
      animal genome sequencing will provide a great deal of new information. A major
      challenge for the years to come will be using this information in a
      physiologically meaningful context and to continue the efforts to convert the
      laboratory experience into use in practise. Finally, it is important to obtain
      societal acceptance for a wider application of many of the technologies, such as
      in vitro embryo production and cloning.

PMID- 14972161
TI  - Regarding "fecal impaction: a fatal cause of cardiac tamponade?".

PMID- 14972162
TI  - Antibiotic allergy: guidelines for antibiotic choice and treatment of severe drug
      reactions.

PMID- 14972163
TI  - The evolution of the link between surgical outcomes and volume: how we got to
      "Leapfrog".

PMID- 14972164
TI  - Abdominal closure in the critically ill patient.

PMID- 14972165
TI  - Applications of videothoracoscopy in cardiothoracic trauma.

PMID- 14972166
TI  - Liver trauma: a victory for conservative approaches.

PMID- 14972167
TI  - Orbital fractures: a review of current literature.

PMID- 14972168
TI  - Pelvic fractures and the general surgeon.

PMID- 14972169
TI  - Recent advances and current controversies on the modern management of blunt
      injury to the descending thoracic aorta.

PMID- 14972170
TI  - Tracheostomy: timing revisited.

PMID- 14972171
TI  - The history of open inguinal hernia repair.

PMID- 14972172
TI  - Current laparoscopic inguinal hernia repair.

PMID- 14972173
TI  - The 25th Gary P. Wratten Army Surgical Symposium.

PMID- 14972174
TI  - Is routine ultrasound guidance for central line placement beneficial? A
      prospective analysis.
AB  - OBJECTIVE: Portable ultrasound devices have become more readily available in the
      intensive care unit setting, but their utility outside of controlled trials
      remains unproven. We sought to determine how the availability of ultrasound
      guidance affected the types and number of complications during central line
      placement. DESIGN: Review of a prospectively maintained database in a 20-bed
      combined intensive care unit. Procedure notes from all attempts at internal
      jugular vein access from 1996 to 2001 were recorded, and selected patient records
      were reviewed. Ultrasound guidance was available beginning in March 1998.
      RESULTS: From 1996 to 2001, there were 484 documented attempts at internal
      jugular central line placement. Most procedures (83%) were performed by first- or
      second-year residents. During this period, there were 47 complications for an
      overall complication rate of 10%. These included 1 pneumothorax (2%), 6 carotid
      punctures (13%), 2 hematomas (4%), and 34 unsuccessful attempts (72%). There was
      no significant difference in age, sex, body-mass index, or intubation status
      between those with and without complications or between the ultrasound and
      anatomic landmark groups. Ultrasound was used in 179 (37%) attempts. The overall
      complication rate with ultrasound was 11% versus 9% using anatomic landmarks (p =
      NS). The complication rate prior to the availability of ultrasound was 15 of 114
      attempts (13%) versus 32 of 370 attempts (9%) after the introduction of
      ultrasound in our intensive care unit (p = NS). Analysis of the 370 procedures
      performed since ultrasound became available demonstrated a complication rate of
      11% with ultrasound guidance versus 6% without (p = 0.09). There was no
      significant difference in complication rates by resident year group or department
      (surgery vs. other). However, procedures performed after-hours (1800 to 0800)
      were associated with a 15% complication rate versus 6% for procedures performed
      during the workday (p < 0.05). CONCLUSION: The availability and use of ultrasound
      guidance for central line placement by junior residents has not resulted in an
      improvement in procedure-related complications. The complication profile was not
      affected by ultrasound use, patient factors, or resident year in training. There
      was a higher complication rate associated with procedures performed at night that
      may be caused by resident fatigue or unavailability of senior supervision.

PMID- 14972175
TI  - Namesake biography: Dwight David Eisenhower Army Medical Center.

PMID- 14972176
TI  - Sepramesh vs. Dualmesh for abdominal wall hernia repairs in a rabbit model.
AB  - PURPOSE: To compare the relative strength of incorporation and adhesion formation
      for mesh hernia repairs performed with Sepramesh (Genzyme Corp., Cambridge,
      Massachusetts) and Dualmesh (WL Gore and Assoc., Flagstaff, Arizona). METHODS: A
      prospective randomized study was conducted using 30 New Zealand white rabbits,
      with 15 animals randomized to each limb. A standardized abdominal defect was
      created in each animal. The defect was then repaired using either Sepramesh or
      Dualmesh. Animals were sacrificed at 4 weeks. The area of adhesions was
      determined using digital analysis of inked specimens. Strength of incorporation
      was determined using an Instron Tensiometer. (Department of Clinical Research, D.
      D. Eisenhower Army Medical Center, Fort Gordon, GA 30905.) RESULTS: Sepramesh had
      a 30.6% stronger strength of incorporation compared with Dualmesh. (p = 0.011)
      The difference in area of adhesions was not statistically significant between the
      2 products. CONCLUSIONS: The use of Sepramesh for abdominal hernia repairs
      provides a significantly stronger strength of incorporation without increasing
      the amount of adhesions as compared with Dualmesh.

PMID- 14972177
TI  - Dysphagia and weight loss in a middle-aged man.

PMID- 14972178
TI  - Current status of gene therapy for pancreatic cancer.
AB  - Pancreatic adenocarcinoma remains a widespread and difficult disease to treat.
      Surgical resection offers the possibility of cure in a select few. However, most
      patients are not eligible, and conventional chemotherapy and radiation remain
      largely ineffective. Despite this, our understanding of the pathogenesis of the
      disease has advanced considerably over the past few decades. These findings
      provide the basis for the development of much needed new therapeutic modalities.
      Specifically, the application of new recombinant DNA technology and techniques to
      pancreatic cancer has yielded promising results. This paper reviews our current
      understanding of the molecular biology of pancreatic adenocarcinoma and its
      applications to the field of gene therapy.

PMID- 14972179
TI  - Faculty development programs promote the academic advancement of the faculty.

PMID- 14972180
TI  - Surgical lessons from Shakespeare.

PMID- 14972181
TI  - Changes I experienced as a resident.

PMID- 14972182
TI  - Current changes in residency: a view from the front line.

PMID- 14972183
TI  - Habits of mind.

PMID- 14972185
TI  - Are you a surgical role model?
AB  - PURPOSE: Multiple papers have examined the recent decline in the number of
      surgical residency applicants. Many have concluded that a lack of role models in
      surgery is at least partially responsible for this decline. However, to date, the
      definition of a surgical role model does not exist. This paper defines a surgical
      role model based on criteria determined by surgery residents. METHODS: Fourth-
      and fifth-year surgical residents from 1 residency program were asked to
      collaboratively define 9 characteristics that make a surgical role model. The 9
      criteria as defined by the residents were didactic teaching, teaching rounds,
      attendance at didactic activities, demonstrates skills and decision making in the
      operating room with confidence and virtuosity, allows [resident] to do procedures
      according to ability, allows autonomy to make independent decisions, provides
      feedback, stimulates critical thinking with use of literature, and assists
      [resident] to find and complete research for publication. Each resident in the
      program was then given a questionnaire and asked to evaluate each of the 49
      teaching attendings on each of the 9 criteria, on a 3-point scale. Finally,
      residents evaluated each attending based on professionalism and mutual respect on
      a scale of I Don't Want To Emulate Him/Her, OK, or Role Model. These categories
      were also assigned a number (1, 2, and 3, respectively). Pearson correlation and
      stepwise multiple regression were used to determine the relationship between
      "Role Model" and the 9 criteria. The unit of analysis was the mean rating given
      each attending on each of the 10 scales. RESULTS: A total of 847 questionnaires
      were analyzed. Each of the 9 criteria correlated significantly with the Role
      Model rating (all p < 0.01). The average correlation was 0.73 (range, 0.64 to
      0.78). Of the 9 criteria, 4 correlated best with the Role Model, as shown in. The
      stepwise regression indicates that 3 of the 9 criteria are uniquely associated
      with the Role Model variable. These 3 criteria are stimulates critical thinking
      with use of literature, allows autonomy to make independent decisions, and
      attendance at didactic activities. CONCLUSIONS: All of the 9 criteria are
      important factors in residents' perception of the Role Model characteristics of
      attending faculty. A parsimonious, operational definition of the surgical
      attending role model is one who stimulates the resident to think, gives the
      resident the opportunity to think and act independently, and is available to the
      resident.

PMID- 14972186
TI  - Presidential address: forgive and remember while punching the clock.

PMID- 14972187
TI  - Web-based minimally invasive surgery training: competency assessment in PGY 1-2
      surgical residents.
AB  - OBJECTIVES: Little published literature describes accurate evaluation and
      assessment of surgical residents' technical competencies. Work-hour limitations
      and the proposed changes in training duration challenge our ability to provide
      core technical competencies, particularly during PGY-1-2. We identified minimally
      invasive surgery as a particularly challenging competency training area,
      requiring significant allocation of resident and faculty time and resources, with
      inconsistent training results. This project evaluated a standardized competency
      training curriculum in minimally invasive surgery in comparison to existing
      training. METHODS: The Laparoscopy 101-a Resource for Resident Education
      minimally invasive surgery competency training curriculum consists of CD-ROM
      based self-paced didactic self-instruction modules, skills laboratories, and web
      based testing, evaluation, and reporting. Five didactic self-study modules and
      their corresponding web-based examinations were selected for this study. PGY 1-2
      residents (11/group) were enrolled. PGY-1 residents received no formal minimally
      invasive surgery training in our program before participating, whereas PGY-2
      residents were exposed to the minimally invasive surgery training program in
      place in our department. PGY-1 residents completed the training modules and web
      based testing over 4 days. PGY-2 residents underwent testing before (pre-test)
      and after (post-test) completing identical training modules and testing over an
      identical time period. Test results were examined and compared in both groups. A
      user-satisfaction survey assessed resident opinions about the quality of the
      curriculum, use of the CD-ROM/web-based system, and trainee perceptions about
      performance. RESULTS: PGY-2 Pre-test scores were equivalent to PGY-1 scores after
      training (mean overall performance, 52.4% vs 65.5% p = ns). PGY-2 Post-test
      scores were significantly higher when compared with pre-test scores (mean overall
      performance; pre: 52.4% vs post: 85.3% p <== 0.001). Interestingly, post-training
      scores were significantly higher for PGY-2 than PGY-1 (mean overall performance
      PGY-1: 52.4% vs PGY-2: 65.5% p = ns). Competencies achieved persisted 6 months
      after initial training in both PGY 1-2 groups without additional training using
      this curriculum. Overall user satisfaction was positive in each category
      evaluated. CONCLUSIONS: The Laparoscopy 101 minimally invasive surgery curriculum
      (1) p;rovides a structured self-paced curriculum for minimally invasive didactic
      training that is well accepted by trainees; (2) yields PGY-1 competencies
      equivalent to PGY-2 who receive training in our department's existing program;
      and (3) yields significant improvement in PGY-2 minimally invasive surgery
      competencies. Training effects persist to 6 months without reinforcement. Our
      observations of PGY-2 performance and competency suggest that this training would
      best be instituted during PGY-2.

PMID- 14972188
TI  - Surgical stress: a basic critical concept or is it just voodoo?

PMID- 14972189
TI  - I can't sing anymore: voice changes after thyroidectomy.

PMID- 14972190
TI  - Laparoscopic adrenalectomy for pheochromocytoma.

PMID- 14972191
TI  - Location, location, location: finding the elusive parathyroid.

PMID- 14972192
TI  - Review of parathyroid surgery.

PMID- 14972193
TI  - How will limiting resident work hours impact surgical training?

PMID- 14972194
TI  - Current management of pancreatic pseudocysts.

PMID- 14972195
TI  - Minimally invasive approaches to pancreatic pseudocysts.

PMID- 14972197
TI  - A physician's professional duty to inform despite personal ethical objections.

PMID- 14972198
TI  - Compensatory justice in affirmative action.

PMID- 14972199
TI  - Organ transplantation by prisoners--considerations of commuted sentences.

PMID- 14972200
TI  - The value of deaf culture: should states have the right to mandate placement of
      cochlear implants?

PMID- 14972201
TI  - Gastric outlet obstruction as a consequence of a duodenal web masquerading as
      gastrinoma in an adult.
AB  - We present the case of a 24-year-old man with recurrent peptic ulcers and
      hypergastrinemia, in whom a multidisciplinary investigation for gastrinoma
      revealed a duodenal web. The affected duodenal segment was excised, and a
      gastroduodenostomy with highly selective vagotomy was performed. Postoperative
      serum gastrin levels returned to the normal range over the next 6 weeks.
      Congenital duodenal anomalies are unusual causes of gastric outlet obstruction in
      adults. Chronic gastric outlet obstruction secondary to an adult duodenal web can
      induce neurohumoral changes in gastric function, which enhance both acid output
      and gastrin secretion. This case reminds clinicians to consider congenital
      anomalies in adults presenting with recurrent peptic ulcers and hypergastrinemia.

PMID- 14972202
TI  - Perioperative management of diabetic patients.
AB  - Diabetes mellitus is the most common metabolic disease. New classifications have
      recently been proposed by the American Diabetes Association (ADA) and the World
      Health Organization (WHO). Type 1 (formerly insulin-dependent diabetes mellitus
      IDDM) is immune-mediated and leads to absolute insulin deficiency. Type 2
      diabetes (formerly non-insulin-dependent diabetes mellitus [NIDDM]) is a disease
      of adult onset and is associated with insulin resistance. Type 3 corresponds to a
      wide range of specific types of diabetes, including various genetic defects of
      beta-cell function and insulin action, diseases of exocrine pancreas,
      endocrinopathies, and drug-induced diabetes. Type 4 is gestational diabetes
      (Table 1). Diabetics undergoing surgery have increased mortality, and type 1
      diabetics are particularly at risk of postoperative complications. Wound
      complications are increased in diabetics, and healing is severely impaired when
      glycemic control is poor. However, with the use of modern management plans, the
      major outcome measures of surgery are comparable in diabetic and nondiabetic
      patients. Successful management of surgery in diabetic patients requires simple
      and safe protocols, which are fully understood by all staff and a close liaison
      among the surgeons, diabetes care team, and anesthetists. There is no consensus
      on the optimal metabolic management of the diabetic patient during surgery.
      Several surveys have highlighted the inconsistency with which surgical problems
      are managed in diabetic patients. The aim of this article is to provide protocols
      to achieve sensible and practical glycemic control in diabetic patients
      undergoing surgery.

PMID- 14972203
TI  - Postoperative home visits?
AB  - PURPOSE: Because most surgery patients now recover at home rather than in the
      hospital, we wanted to determine whether postoperative home visits by the
      operating surgeon would improve medical outcomes, and whether this innovation
      would strengthen resident training. METHODS: A surgeon who had performed 347
      procedures during a 7-month period attempted to do a home visit to each patient
      within 48 hours after surgery. RESULTS: Many patients had to be disqualified for
      various reasons, leaving 143 candidates. Of these, 44 declined to be seen, and
      others could not be located, so that 82 were actually visited. There were no
      readmissions, and no findings that might have altered the course of postoperative
      treatment. CONCLUSIONS: These visits seemed to reinforce patient-physician
      relationships, but they did not influence medical outcomes. It was felt that a
      phone call would probably have done as well. In addition, because of new
      regulations governing resident working hours, it did not appear that this was a
      feasible educational experience.

PMID- 14972204
TI  - The effect of standardized patient feedback in teaching surgical residents
      informed consent: results of a pilot study.
AB  - PURPOSE: The purpose of this pilot study was to determine the effectiveness of
      using feedback from a standardized patient (SP) to teach a surgical resident (SR)
      informed consent (IC) protocol. METHODS: Four general case types of increasing
      difficulty were tested in a longitudinal experimental design format. The four
      types of cases were appendectomy, cholecystectomy, colorectal cancer, and breast
      cancer. Eight SRs of varying years of completion in medical school served as
      subjects-four in the experimental group (received performance feedback from an
      SP) and four in the control group (received no SP feedback). Both the control and
      experimental groups participated in two patient encounters per case type. The
      first patient encounter served as the pretest, and the second patient encounter
      was the posttest. In each encounter, an SP rated the resident on 14 measures
      using an open-ended seven-point rating scale adopted and modified from the Brown
      University Interpersonal Skill Evaluation (BUISE). Each resident also reviewed a
      videotape of an expert giving IC between pretest and the posttest for basic
      instructional protocol. Random stratified sampling was used to equally distribute
      the residents by postgraduate years. A total of 16 SPs were used in this study.
      All patient/SR encounters were videotaped. RESULTS: There was a statistically
      significant overall change--pretest to posttest and across cases (p = 0.001). The
      group effect was statistically significant (p = 0.000), with the experimental
      group averaging about 10 points greater than the control group. CONCLUSIONS:
      Standardized patient feedback is an effective modality in teaching surgical
      residents informed consent protocol. This conclusion is tentative, due to the
      limitations of sample size. The results of this study support continued research
      on the effects of standardized patient feedback to teach informed consent to
      surgical residents.

PMID- 14972206
TI  - Early leukocytosis in trauma patients: what difference does it make?
AB  - OBJECTIVE: To determine the association of the admission white blood cell count
      in trauma patients with demographics, severity and mechanism of injury, and need
      for therapeutic intervention. METHODS: Evaluation of prospectively collected
      registry data (admissions to a Level I trauma center in 2001). Differences in
      mean white blood cell count on admission were evaluated with t tests. Multiple
      linear regressions were performed with forward stepwise selection of variables.
      RESULTS: Of the 882 patients admitted for greater than 24 hours, white blood cell
      count was available for 786. Variations in white blood cell count were noted on
      bivariate analysis among different races, injury mechanisms and severities,
      Glasgow Coma Scores, blood pressures, and between patients requiring early
      transfusions versus those who did not. No difference was noted between patients
      who went to the operating room in the first 24 hours versus those who did not, or
      for patients who died in the hospital. On multiple linear regression analyses,
      only ISS greater than 15, GCS less than or equal to 8, and white race were
      associated with increases in white blood cell count. Leukocytosis was found not
      to be associated with mechanism of injury, specific organ injury, shock on
      admission, or the need for transfusion or surgery. CONCLUSION: Variations in
      white blood cell count in trauma patients are associated with race and injury
      severity, but they are not beneficial in predicting the need for volume
      resuscitation, transfusion, or surgery.

PMID- 14972207
TI  - The telecommunication revolution in the medical field: present applications and
      future perspective.
AB  - In the present review, we analyze the achievements of telecommunication
      innovations in the medical field focusing on patient care and medical-education
      aspects. In this regard, the telecommunication revolution has offered medical
      professionals the possibility to transmit information of any sort zeroing
      transmission time latency and annihilating spatial distances. Although
      telemedicine is still in its infancy, multiple applications of this science have
      already been successfully tested. As an example, robotically mediated telesurgery
      has it made possible for surgeons to operate standing at a considerable distance
      from the operating table without even touching or directly seeing the surgical
      field. Moreover, medical education and medical consulting have acquired new and
      wider ranges of applicability thanks to the introduction of teleproctoring,
      telementoring, and teleconsulting. Finally, in the very near future, telepresence
      surgery will permit "virtual" operations on patients where surgeons can project
      their manual dexterity, psychomotor skills, and problem-solving ability to remote
      locations. In this context, telemedicine will support a more equal distribution
      of medical knowledge and promote excellence in patients' care even in the most
      disadvantaged environments.

PMID- 14972208
TI  - William Worrall Mayo--a forward-thinking physician.

PMID- 14972209
TI  - In vitro fertilization: who is in charge?

PMID- 14972210
TI  - Chronic pancreatitis: surgery can be effective.

PMID- 14972211
TI  - Traumatic corneal abrasions: a review of the current literature.

PMID- 14972212
TI  - Non-small cell lung cancer: an update.

PMID- 14972213
TI  - We interrupt this column; potential virus passed to you.

PMID- 14972214
TI  - Acute appendicitis: current diagnosis and treatment.

PMID- 14972215
TI  - Current status of laparoscopic appendectomy.

PMID- 14972216
TI  - Adult malrotation: a case report and review of the literature.
AB  - Midgut malrotation is an anomaly of fetal intestinal rotation that usually
      presents in the first month of life. It is rare for malrotation to present in
      adulthood. Symptomatic patients present either acutely with bowel obstruction and
      intestinal ischemia with a midgut or cecal volvulus, or chronically with vague
      abdominal pain. Chronic symptoms can often make the diagnosis difficult. Findings
      diagnostic of malrotation are described using several modalities such as barium
      studies, computed tomography (CT) scans, angiography, and often emergent
      laparotomy. Treatment remains the Ladd procedure originally described by Dr. Ladd
      in 1936. Complete resolution of acute obstruction or chronic abdominal pain is
      the result of a high index of suspicion for malrotation, appropriate diagnostic
      studies, and aggressive definitive surgical treatment. We present a case of
      malrotation in an adult who presented with chronic abdominal pain. Midgut
      malrotation is a congenital anomaly referring to either lack of or incomplete
      rotation of the fetal intestines around the axis of the superior mesenteric
      artery during fetal development. Most patients present with bilious vomiting in
      the first month of life because of duodenal obstruction or a volvulus. It is rare
      for this condition to present in adulthood. The true incidence in adults is
      difficult to estimate because most patients who remain are asymptomatic and their
      conditions are, therefore, never diagnosed. A literature review by von Flue et al
      cites 40 cases from 1923 to 1992. Patients who are symptomatic often present
      either acutely with bowel obstruction and intestinal ischemia with a midgut or
      cecal volvulus or chronically with vague abdominal pain. These symptoms are
      caused by peritoneal bands first described by Ladd in 1932. These bands run from
      the cecum to the right lateral abdominal wall. We present a case of malrotation
      in an adult who presented with chronic abdominal pain.

PMID- 14972217
TI  - Cancer in the gastric remnant after gastric bypass: a case report.
AB  - Gastric cancer in the gastric stump after a Bilroth II subtotal gastrectomy is a
      well-recognized entity. However, gastric cancer in the bypassed gastric remnant
      after a gastric bypass operation for morbid obesity has not been well described,
      and only 2 such cases have been reported in the English literature. This case
      report presents a patient who developed gastric cancer in the defunctionalized,
      bypassed stomach 22 years after undergoing an open gastric bypass with a Roux-en
      Y gastro-jejunostomy for morbid obesity. The problems of monitoring the
      defunctionalized bypassed stomach after gastric stapling and gastro-jejunostomy
      are discussed.

PMID- 14972218
TI  - Radiosurgical fistulotomy; an alternative to conventional procedure in fistula in
      ano.
AB  - PURPOSE: Most surgeons continue to prefer the classic lay open technique
      [fistulotomy] as the gold standard of treatment in anal fistula. In this
      randomized study, a comparison is made between conventional fistulotomy and
      fistulotomy performed by a radio frequency device. MATERIALS AND METHODS: One
      hundred patients of low anal fistula posted for fistulotomy were randomized
      prospectively to either a conventional or radio frequency technique. Parameters
      measured included time taken for the procedure, amount of blood loss,
      postoperative pain, return to work, and recurrence rate. RESULTS: The patient
      demographic was comparable in 2 groups. The radio frequency fistulotomy was
      quicker as compared to a conventional one [22 versus 37 minutes, p = 0.001],
      amount of bleeding was significantly less [47 ml versus 134 ml, p = 0.002], and
      hospital stay was less when patient was operated by radio frequency method [37
      hours versus 56 hours in conventional method, p = 0.001]. The postoperative pain
      in the first 24 hours was more in conventional group [2 to 5 versus 0 to 3 on
      visual analogue scale]. The patients from radio frequency group resumed their
      duties early with a reduced healing period of the wounds [47 versus 64 days, p =
      0.01]. The recurrence or failure rates were comparable in the radio frequency and
      conventional groups [2% versus 6%]. CONCLUSIONS: Fistulotomy procedure using a
      radio frequency technique has significant advantages over a conventional
      procedure with regard to operation time, blood loss, return to normal activity,
      and healing time of the wound.

PMID- 14972219
TI  - Reducing the noneducational and nonclinical workload of the surgical resident;
      defining the role of the health technician.
AB  - PURPOSE: Recent controversy over excessive resident work hours has prompted
      surgical educators and program directors to search for more efficient methods to
      limit the nonclinical and noneducational workload of surgical residents. Health
      technicians were employed at a large Veteran's Administration Medical Center to
      allow residents more time for direct patient care in the clinics and wards and in
      educational activities. METHODS: In a two-week period, daily data cards were
      collected from each intern and health technician identifying total hours spent in
      work, operations, clinics, and conferences. Each intern recorded the number and
      type of tasks performed and those tasks assigned to the health technician. The
      number and type of task performed were tabulated and averaged for each health
      technician and physician. RESULTS: Each intern (n = 3) and health technician (n =
      8) completed 100% of the required data forms. In a control survey, each intern
      worked a mean of 16.9 hours per weekday and 5.0 hours per weekend day. With the
      addition of the health technicians, interns worked 12.9 hours per weekday and 6.8
      hours per weekend day (when the health technicians were not present). Following
      the addition of the health technicians, resident time in the operating room
      increased from 3.3 hours per week to 9.8 hours per week. Each health technician
      aided the intern by performing an average of 20.25 tasks per day. CONCLUSIONS:
      This study shows that health technicians can be effective in reducing the overall
      hours and workload of surgical residents and increasing time spent in the
      operating room. Consideration should be given to including the health technician
      as integral members of the health care team in the teaching hospital.

PMID- 14972220
TI  - Surgery residents' perception of the Objective Structured Clinical Examination
      (OSCE).
AB  - PURPOSE: Beginning in July 2003, residency programs will be required to
      incorporate new educational assessment methods as defined by the Accreditation
      Council for Graduate Medical Education (ACGME) outcome initiative. The Objective
      Structured Clinical Examination (OSCE) is an assessment tool that is favorably
      viewed by the ACGME. Our institution has utilized the OSCE for evaluation of
      surgery trainees since 1996. Despite the positive acceptance of the OSCE by
      students, residents expressed dissatisfaction with the examination. This study
      was therefore undertaken to specifically evaluate resident perception of the
      OSCE. METHODS: Two sequential surveys were administered to surgery residents at
      the Medical College of Ohio. Response of medical students to a standard survey
      following completion of the OSCE was tabulated. RESULTS: On the first, general
      survey, residents felt that the OSCE was not an adequate measure of either
      clinical (15 of 17 residents) or technical (15 of 18 residents) skills; 14 of 16
      residents felt that the OSCE should not be used when considering promotion. When
      specifically queried in a follow-up survey, residents indicated that the OSCE was
      an adequate measure of clinical knowledge (2.2 +/- 0.3); however, most still felt
      that the OSCE should not be used when considering promotion (4.3 +/- 0.3).
      (Scores = mean +/- SEM on a Likert scale where 1 = strongly agree and 5 =
      strongly disagree). By contrast, 97.6% of 663 medical students surveyed
      (September 1996 through February 2002) felt the OSCE was useful. CONCLUSIONS: The
      OSCE has been shown to be a reliable and valid measure of basic clinical and
      technical competence. Despite our residents' current perception, we believe that
      the OSCE is an important method for resident evaluation, particularly within the
      context of the current ACGME outcome initiative.

PMID- 14972221
TI  - Transvaginal local excision of rectal carcinoma.
AB  - PURPOSE: To recommend a new approach-transvaginal local excision of early rectal
      cancers-and report the results of the approach applied by dedicated surgeons at a
      specialized colorectal unit during a 10-year period. METHODS: The surgical
      outcome of 18 patients undergoing transvaginal local resection between January
      1991 and August 2001 was reviewed. Patients were identified according to the
      consultants' personal records and cross-referenced with the operating room logs.
      Data were collected retrospectively, and follow-up was performed on all patients.
      RESULTS: A total of 18 patients underwent 18 procedures during the study period.
      Follow-up ranged from 2 months to 104 months. There were no treatment-related
      complications. Two patients suffered from recurrences at a median follow-up time
      of 35.7 months, but they underwent subsequent surgical treatment: APR (one) and
      LAR (one). No evidence of disease was found during a median follow-up of 20
      months (12 and 28 months). No one died. CONCLUSIONS: Transvaginal local excision
      is an alternative and feasible technique with low rates of death and
      complications for the treatment of rectal cancer in strictly selected cases.

PMID- 14972223
TI  - An emotional war on the wards.

PMID- 14972224
TI  - Advice to attendings.

PMID- 14972225
TI  - Attending-resident relations 101.

PMID- 14972226
TI  - Surgical education and the mentor-student relationship.

PMID- 14972227
TI  - Will Camp Sealy, MD: father of arrhythmia surgery.

PMID- 14972228
TI  - Personal computers versus patient care: at the desktop or at the bedside?

PMID- 14972229
TI  - Cures for Windows headaches and pesky program peccadilloes.

PMID- 14972230
TI  - An introduction to laparoscopic gastric resection.

PMID- 14972231
TI  - Leonard Heaton oration: The United States Military Cancer Institute--realities
      and potentialities.

PMID- 14972232
TI  - Acute lung injury using oleic acid in the laboratory rat: establishment of a
      working model and evidence against free radicals in the acute phase.
AB  - OBJECTIVE: To determine the optimal model of acute respiratory distress syndrome
      (ARDS) using oleic acid in our laboratory and to measure the presence or absence
      of free radicals in this model. DESIGN: This protocol consisted of 2 phases.
      During the first phase, various conditions were tested, to include different
      doses (30 or 50 microliters) of oleic acid, different levels of support (with and
      without mechanical ventilation), and different injury time periods (sacrifice 4
      or 8 hours after injection). During the second phase, animals were randomly
      assigned to experimental (injured) and control (noninjured) groups for the
      measurement of free radicals by nitrotyrosine Western blot and by the conversion
      of hydroethidine to ethidium bromide by superoxide. SETTING: Multidisciplinary
      laboratory and animal surgery suite. PARTICIPANTS: Twenty-seven male Sprague
      Dawley rats. RESULTS: During the first phase, several animal deaths occurred in
      the high-dose, ventilated groups, whereas there were no deaths in the
      nonventilated animals. On hematoxylin and eosin stain, injury was greatest in the
      animals that received the higher dose of oleic acid and that were sacrificed at 8
      hours. In the protocol's second phase, oxygen radical assays were negative for
      all experimental and control lungs. CONCLUSIONS: During this study, we
      successfully established a working animal model of ARDS for our laboratory. Our
      findings to date suggest that free radicals do not contribute to oleic acid lung
      injury in the early stages.

PMID- 14972233
TI  - Forward surgical team (FST) workload in a special operations environment: the
      250th FST in Operation ENDURING FREEDOM.
AB  - PURPOSE: Forward Surgical Teams (FST) deploy to support conventional combat units
      of at least regimental size. This report examines the injuries and treatments of
      an FST in an environment of unconventional tactics, limited personal protection,
      and extended areas of responsibility during Operation ENDURING FREEDOM. METHODS:
      A prospective evaluation of the personal protective measures, mechanisms of
      injury, types of injuries, and times to treatment in Operation ENDURING FREEDOM.
      Additionally, per-surgeon caseloads, operative interventions, and outcomes are
      examined. The first phase of this deployment involved co-locating with an Air
      Force Expeditionary Medical Squadron at Seeb Air Base, Oman (SABO). The second
      phase involved stand-alone operations at Kandahar International Airport (KIA).
      Participants include U.S. Special Forces, conventional U.S forces, coalition
      country special forces, and anti-Taliban Afghan soldiers. RESULTS: During the
      deployment, the FST performed 68 surgical procedures on 50 patients (19 SAB, 31
      KIA). There were 35 orthopedic cases (2 to 28 per surgeon), 30 general surgery
      cases (2 to 10 per surgeon), and 3 head/neck cases. Mechanism of injury included
      non-battle injury (13), bomb blast (13), gunshot wounds (8), mine (8), and
      grenades (5). Primary injuries were to the extremities in 27, torso in 9, and
      head/neck in 11. Three patients had appendicitis. Five patients were wearing body
      armor, whereas 4 wore helmets. The mean Relative Trauma Score was 7.4. Thirty-one
      patients were treated at KIA with a mean time to operative treatment of 2.7 +/-
      2.7 hours, whereas 19 were treated in SABO with a mean time to operative
      treatment of 12.4 +/- 15.1 hours. Nine patients received transfusions. Three
      nonoperative patients died of wounds. CONCLUSION: Despite the lack of personal
      protective gear, most patients had extremity wounds as their primary injuries. In
      this special operations environment, time to operative treatment was
      significantly longer than expected.

PMID- 14972234
TI  - Use of recombinant FVIIa for intraperitoneal coagulopathic bleeding in a septic
      patient.

PMID- 14972235
TI  - Rectal bleeding in a woman with a thyroid mass.

PMID- 14972236
TI  - Adrenal gland trauma is associated with high injury severity and mortality.
AB  - PURPOSE: To review a statewide experience of adrenal gland trauma (AGT),
      incidence, demographics, associated injuries, Injury Severity Score (ISS),
      Glasgow Coma Scale (GCS), mechanisms of injury, and complications, associated
      with AGT. METHODS: A retrospective analysis of patients admitted to accredited
      trauma centers in the Commonwealth of Pennsylvania who sustained AGT from January
      1, 1989 to December 31, 2000. RESULTS: Adrenal trauma was found in 322 of 210,508
      cases (0.15%). There were 76.4% men and 23.6% women. Seventy-one percent of
      patients had an ISS greater than 20. The overall mortality was 32.6%. The
      mechanism of injury was blunt in 81.4% of the cases and penetrating in 18.6%.
      Vehicular accidents constituted 48.8% of the cases. Younger age was associated
      with male predominance and greater proportion of penetrating injuries. Although
      exact indications are not known, advanced imaging studies were done in 163 of 322
      (50.6%) patients: computed tomography in 133 (41.3%), ultrasound in 26 (8.1%),
      and angiography in 4 cases (1.2%). Exploratory laparotomy was done in 60 (18.6%),
      splenectomy in 25 (7.8%), nephrectomy in 14 (4.3%), and adrenalectomy in 8
      (2.5%). Penetrating injuries had a 43.8% rate of exploratory laparotomy, whereas
      it was 12.4% in blunt trauma. Associated injuries included liver injury (57.8%),
      rib fractures (50.9%), kidney injury (41.3%), and spleen injury (32.9%).
      Pulmonary complications were most common, followed by infection/sepsis, and
      cardiovascular. Nearly 45% of patients were discharged home, 17% of patients were
      discharged to a rehabilitation facility, and 3.4% to nursing homes. CONCLUSIONS:
      Adrenal gland trauma is a rare and largely coincidental finding diagnosed either
      during an initial radiologic examination or surgical exploration for other
      injuries. Surgical exploration was carried out in 21.4% of patients, with
      adrenalectomy in 2.5% of cases and nephrectomy in 4.3% of cases. Adrenal injury
      is associated with high injury severity, and with mortality rates up to 5 times
      higher than non-AGT trauma.

PMID- 14972237
TI  - Endoluminal reconstruction of the canine common biliary duct.
AB  - PURPOSE: Extrahepatic biliary duct injuries such as transections, stenoses, and
      biliary leaks are well-known complications of upper abdominal surgeries. The
      popularization of laparoscopic cholecystectomies in the early 1990's resulted in
      an increase in the numbers of these reported injuries. The surgical repair of
      these injuries may be challenging. In this feasibility study, we were presented
      with the opportunity to evaluate a novel polytetrafluoroethylene (PTFE) covered
      stent graft that could be useful in common bile duct reconstructions. The long
      term goal of this research is to offer the surgeon a new technique for
      reconstructing the biliary duct or repairing biliary strictures.John G.
      Zografakis MD, was the first place winner in the Basic Sciences Resident
      Competition at the Ohio American College of Surgeons meeting. METHODS: Seven dogs
      were originally enrolled in the study. After general endotracheal anesthesia and
      open cholecystectomy, the common bile duct was identified in each dog. A guide
      wire was then passed through the neck of the cystic duct, anterograde into the
      common bile duct, through the Ampulla of Vater and into the duodenum. A stent
      graft delivery system was placed over the wire, and the covered stent graft was
      deployed within the lumen of the common bile duct. Study outcomes included graft
      patency and assessment of the bio-incorporation of the graft and the
      effectiveness of the graft to drain the biliary system as determined by liver
      enzyme tests. RESULTS: Three implants were harvested at 1 month, and 2 grafts
      were harvested each at 3 months and 6 months postoperatively. All of the stent
      grafts were patent. Liver enzyme tests revealed that all dogs had increased serum
      levels of alkaline phosphatase, alanine aminotransferase (ALT) serum glutamate
      pyruvate transaminase (SGPT) and aspartate aminotransferase (AST) serum glutamic
      oxaloacetic transaminase (SGOT). Four dogs had increased total bilirubin. These
      increases were all measured in the immediate postoperative period. Peak levels
      for each measure were reached between 4 and 10 days and then gradually trended
      toward baselines by 1 month postoperatively. We did not observe meaningful
      changes in serum albumin or total protein. One dog suffered a tear in the common
      bile duct due to balloon overinflation. This tear was suture repaired when the
      graft was implanted. However, bile leakage was found when the graft was harvested
      at 1 month postoperatively. There appeared to be minimal bio-incorporation of the
      stent-grafts into the biliary duct wall, and there was no pronounced inflammatory
      response found in the duct wall or surrounding tissues. CONCLUSIONS: We are
      encouraged by these early results. Additional studies are planned to evaluate a
      self-expanding PTFE covered stent graft and a percutaneous delivery system.

PMID- 14972238
TI  - Feasibility of a novel veno-veno circuit as a central rewarming method in a
      severely hypothermic canine model.
AB  - PURPOSE: Many victims of accidental hypothermia are successfully resuscitated,
      but questions remain regarding the optimum rewarming techniques. Most of the
      invasive warming techniques such as closed thoracic lavage, hemodialysis,
      peritoneal dialysis, and cardiopulmonary bypass require specialized personnel,
      equipment, and procedures that are not readily available in all facilities. The
      objective of this study was to investigate the technical feasibility of utilizing
      a novel veno-veno rewarming circuit to resuscitate severely hypothermic subjects.
      If this alternative invasive warming technique is successful, it could be
      available to treat hypothermic patients in virtually any emergency department
      setting. METHODS: The rewarming system consisted of a Baxter ThermaCyl warmer
      (Baxter Co., McGaw Park, IL), a roller pump, hemodialysis tubing, connectors, and
      2 venous catheters. Blood was pumped from the body via the femoral vein, through
      the roller pump, into the warmer, and then returned to the body via the right
      jugular vein. Seven adult mongrel hounds of similar weights (20 to 25 kg) were
      anesthetized and instrumented for data collection. Temperature probes were placed
      in the rectum, the peritoneal cavity, and the esophagus to record core
      temperatures. Each animal was cooled by ice packing to a central core temperature
      of 29 degrees C and then rewarmed using the described veno-veno circuit. Vital
      signs, pulse oximetry, cardiac rhythm, and laboratory values were obtained prior
      to cooling the animals, and were repeated for every degree Celsius change once
      warming began. Christopher Haughn, MD, was the second place winner in the Basic
      Sciences Resident Competition at the Ohio American College of Surgeons meeting.
      RESULTS: Because of technical difficulties, data from 1 dog were not included in
      the results. Of the remaining 6 dogs, all were rewarmed from 29 degrees C to 37
      degrees C. Adverse side effects included gross hematuria, acidemia (median pH
      decrease was 0.088), and decreases in haptoglobin (median decrease 13.5 g/dl),
      hemoglobin (median decrease 1.35 g/dl), and arterial pO(2) level (median decrease
      167 mm Hg). Decreases in blood pressure and heart rate were also noted during the
      cooling process, but reversed upon rewarming. CONCLUSIONS: From this pilot study,
      we conclude that our novel veno-veno circuit rewarming is a feasible method of
      rewarming hypothermic subjects and warrants further investigation and comparison
      with other active warming methods.

PMID- 14972239
TI  - Fecal impaction: a fatal cause of cardiac tamponade?
AB  - Fecal impaction has been an instigator of various morbidities and mortalities.
      Fecal impaction has not been previously implicated by the literature in English
      as a fatal cause of cardiac compression.

PMID- 14972240
TI  - Radio-ablation of advanced grades of hemorrhoids with radiofrequency.
AB  - BACKGROUND: For advanced degree of hemorrhoids with prolapse of the rectal
      mucosa, the choice is hemorrhoidectomy, which could be open, close, diathermy,
      Laser, or stapled one. As an effective alternative to this, in situ radio
      frequency ablation of the pile mass has been found to be quite efficacious with
      many added advantages over the conventional hemorrhoidectomy procedures in
      practice. MATERIALS AND METHODS: This study included 50 patients (34 males and 16
      females) treated at Gupta Nursing Home, Laxminagar, Nagpur, India, with the above
      technique from April 2000 to March 2001 and each case followed up over a period
      of 12 months. RESULTS: In first 4 weeks of the procedure, 14% of patients
      complained of bleeding, whereas all of the patients had some amount of pain.
      Eleven (22%) patients had serosanguinous discharge, but in none of them was there
      any incontinence or prolapse. All of the patients resumed their routine within 1
      week of the procedure. A subsequent follow-up of the patients at an interval of
      12 weeks and 12 months showed significant relief in all of the above early
      postoperative symptoms. During follow-up at the end of 1 year, 7 patients were
      found to have skin tag formation. However, complications like anal stenosis or
      stricture or incontinence was not found in any of the patients. CONCLUSION: For
      advanced degree of piles with prolapse as the main symptom, in situ radio
      frequency ablation can be a better choice to various types of hemorrhoidectomy in
      the sense that the hospital stay is minimized, recurrence is rare, and return to
      work is faster. The results are more assuring when compared with conventional
      hemorrhoidectomy. The technique fits into the parameters for being called the
      gold standard procedure. Except the radio-frequency unit, the procedure needs no
      specialized instrument. It can be performed in any routine surgical setup.

PMID- 14972241
TI  - Scholarly activities--essential to surgical education.
AB  - Research and scholarship are an integral part of a surgical residency program. A
      concerted effort by a Director of Surgical Research and a Residency Program
      Director at the community hospital were successful in addressing this very
      important part of medical education. A questionnaire was designed and data
      gathered on the attitudes and involvement toward research activities of graduates
      over the past 6 years. Increased research and scholarly activity resulted from a
      requirement of completing 2 research projects on time for residents. Over the
      period of this study, the number of published full-length papers, number of
      resident names as authors, number of attending surgeon's names as authors, and
      numbers of presentations made in-hospital, and at local, national, and
      international meetings all increased dramatically. Most strikingly, in 1996,
      there were 4 publications, whereas in 2000, there were 20. Presentations during
      this period included orals, posters, and videos. Each former resident did an
      average of about 3 research projects, of which just over 1 was published.
      Satisfaction with amount and quality of scholarship was over 70%. More than 85%
      of residents fulfilled the criteria for graduation, and more than 50% were
      satisfied with the requirement. On average, each graduate had 1 paper published
      since graduation. Seventy-five percent thought their scholarship had improved
      their career. It is essential in a community hospital residency program that
      resident surgeons be trained in the techniques of research and scholarship. In
      our program, research activity and scholarship have been dramatically improved
      over the past 6 years.

PMID- 14972242
TI  - Surgical management of chronic pancreatitis and the role of islet cell
      autotransplantation.
AB  - Chronic pancreatitis is a disease characterized by disabling pain, inability to
      eat, steatorrhea, and eventual malnutrition. This often results in repeated
      hospitalizations and attempts to control symptoms with various analgesic
      regimens. As a result, the medical treatment of chronic pancreatitis is one of
      symptomatic management. Eventually, in some, nutritional supplementation becomes
      a necessity. For a fortunate few, the disease apparently burns itself out in
      time, lessening pain and improving appetite. In many patients, frustration over
      pain management and repeated hospitalizations leads to surgical treatment.
      Various procedures have been devised but, generally, fall into 2 categories:
      operations to decompress dilated ducts and operations to resect diseased
      pancreas. Results with either approach are unpredictable and often unsuccessful.
      For those without dilated ducts or with recurrent pain after surgery, total
      pancreatectomy has been suggested to remove all inflammatory tissue. This can be
      coupled with islet cell autotransplantation to avoid the dangers of
      pancreatogenic diabetes. Appropriate care of the removed pancreas and islet cell
      separation and purification are critical to this procedure to produce viable
      cells. Dispersed islets have been shown to successfully engraft and function for
      indefinite periods of time. Although insulin independence may not be achieved,
      easier maintenance of blood glucose can usually be realized.

PMID- 14972243
TI  - Identity.

PMID- 14972244
TI  - Are we spending too much time in general surgery residency?

PMID- 14972245
TI  - Length of surgical education.

PMID- 14972246
TI  - Surgical training should be shortened for specialists.

PMID- 14972247
TI  - Wireless computing in health care.

PMID- 14972248
TI  - Are these the changes we want? Commentary on surgical training.

PMID- 14972249
TI  - How will changes in resident work hours affect medical students?

PMID- 14972251
TI  - Resident work hour regulations: comments from New York.

PMID- 14972252
TI  - Complications of combined gastric restrictive and malabsorptive procedures: part
      2.

PMID- 14972254
TI  - Complications of laparoscopic biliopancreatic diversion with duodenal switch.

PMID- 14972257
TI  - Abdominal ventral incisional herniorrhaphy: a brief review.

PMID- 14972258
TI  - Laparoscopic incisional hernia repair: a technical advance.

PMID- 14972259
TI  - C. Walton Lillehei, MD, PhD: a father of open-heart surgery.

PMID- 14972260
TI  - Is the use of plain abdominal radiographs (PAR) a necessity for all patients with
      suspected acute appendicitis in emergency services?
AB  - PURPOSE: Almost all patients with suspected appendicitis have plain abdominal
      radiographies (PAR) at the emergency departments. The aims of this study are to
      evaluate the ability of PAR to diagnose suspected acute appendicitis in patients
      and to predict length of hospital stay (LOS). METHODS: Three blinded radiologists
      retrospectively and separately reviewed the preoperative PARs of all patients
      with suspected appendicitis, who underwent surgery in our hospital for 1 year
      period based on 8 radiologic criteria. The patients were divided into 3 groups
      [acute appendicitis (group 1), perforated appendicitis (group 2), and negative
      appendectomy (group 3)] according to their perioperative and pathological
      findings. The relationship between the presence/absence of the PAR findings and
      the diagnosis and LOS were analyzed. RESULTS: The study consisted of 162 patients
      (103 men, 63.6%). There were 96 (60.5%), 45 (27.8%), and 19 (11.7%) patients in
      groups 1, 2, and 3, respectively. Although there were more men in the study
      overall (p < 0.001), there were more women in groups 2 and 3 than group 1 (p =
      0.004, p < 0.001, respectively). Group 2 had the longest LOS, and Group 3 had the
      shortest LOS (p < 0.001). The generalized air-fluid level was more commonly
      observed in group 2 patients (7 of 45) than in group 1 patients (2 of 98) (p <
      0.05). The LOS was longer in group 3 when the sentinel loop was present on the
      PAR (n = 3) (p = 0.017), and in group 2 when the colon cutoff sign was positive
      (n = 3) on the PAR (p = 0.006). CONCLUSIONS: Our results suggest that PAR is
      rarely beneficial in the diagnosis of acute appendicitis and in the prediction of
      LOS. The PAR may not be a necessity for all patients with suspected acute
      appendicitis.

PMID- 14972261
TI  - Meckel's diverticulitis secondary to carcinoid tumor: an unusual presentation of
      the acute abdomen in an adult.
AB  - This case reports the concomitant findings of carcinoid tumor within a Meckel's
      diverticulum presenting as an acute abdomen in an adult male. Most Meckel's
      diverticula remain asymptomatic throughout life, and symptomatic diverticula are
      virtually nonexistent in older adults. Meckel's diverticulitis is clinically
      indistinguishable from acute appendicitis, and abnormal or symptomatic
      diverticula are generally resected. Surgical treatment of Meckel's diverticula is
      recommended for children during exploration. However, resection is controversial
      in asymptomatic adults. Carcinoid tumors are the most common primary tumor of the
      small bowel. The duration of symptoms before diagnosis varies from 2 to 20 years,
      and half of all patients have incurable abdominal disease at first-look surgery.
      Metastatic events occur most commonly in the liver with a generally poor
      prognosis. Surgical resection is the treatment of choice. Both Meckel's
      diverticula and carcinoid tumor are rare clinical entities, and carcinoid tumors
      occurring within a Meckel's diverticulum are even more uncommon. Thus, the
      natural history is difficult to predict and treatment recommendations vary.
      Solitary, localized, asymptomatic nodules less than 1 cm are generally managed
      with diverticulectomy or segmental resection. Larger or multiple lesions require
      wide excision of bowel and mesentery, and hepatic resection may be required for
      metastatic disease.

PMID- 14972262
TI  - Resident research training conducted in a community hospital general surgery
      residency program.
AB  - PURPOSE: Research is educationally important for surgical residents. However,
      little information exists regarding effective methods for teaching residents
      scientific methodology in a community hospital. This effort describes an
      effective program conducted in a community hospital for enhancing scientific
      opportunities of surgical residents. METHODS: A strong infrastructure that
      supports research is necessary. Dedicated nonsalaried teaching faculty serve as
      mentors and co-investigators. Opportunities to engage in basic research are made
      available in off-campus basic science laboratories. RESULTS: Research
      productivity has been prolific, as demonstrated by numerous publications.
      Residents interested in sub-speciality training have been able to conduct
      research that has made them competitive for fellowships and a wider range of
      practice choices. CONCLUSION: Rigorous research can be effectively taught in a
      community hospital, provided adequate educational and funding support is provided
      and faculty actively mentor residents. Having research capabilities provides
      added incentive for better-qualified medical students to apply to a surgical
      residency position in a community hospital. Research productivity also enhances
      the ability to better recruit new faculty.

PMID- 14972263
TI  - Spontaneous rupture of a wandering spleen: case report and literature review.
AB  - Wandering spleen is a rare clinical entity. The etiology is not precisely known,
      and the management is controversial. Patients may become symptomatic when torsion
      of the pedicle results in pain, ischemia, infarction, or rupture. We present a
      spontaneous rupture of a wandering spleen without any history of trauma.

PMID- 14972264
TI  - Transanal resection of a colonic lipoma, mimicking rectal prolapse.
AB  - PURPOSE: Colonic lipomas are benign tumors usually asymptomatic. Occasionally,
      they may cause symptoms such as bleeding, intussusception, obstruction, or rectal
      prolapse. METHODS: We present a 44-year-old African-American female that
      presented with an 8 cm colonic lipoma protruding through the anal verge. We also
      reviewed all the reported cases in the English literature. RESULTS: The patient
      was treated successfully with transanal resection, which has rarely been done
      before for this large a tumor. CONCLUSIONS: Transanal resection of large benign
      tumors of the rectosigmoid is possible.

PMID- 14972265
TI  - Time will tell.

PMID- 14972266
TI  - American College of Surgeons--the candidate membership.

PMID- 14972267
TI  - Beat the clock: challenges to training the new surgeon.

PMID- 14972268
TI  - Resident work hours: is there such a thing as a free lunch?

PMID- 14972269
TI  - Surgical training, the revolution: work hours limitations.

PMID- 14972270
TI  - History of surgery for breast cancer: radical to the sublime.
AB  - The historic milestones that have brought the surgical management of breast
      cancer to its current state are recounted. The Halsted radical mastectomy, once
      considered the ideal cancer operation, no longer has a place in the routine
      management of patients with breast cancer. Breast conservation in the form of
      segmental mastectomy, axillary node dissection, and radiation is often chosen
      over the modified radical mastectomy, popular in the 1980s. Axillary
      lymphadenectomy, shown to be of questionable therapeutic value in breast cancer,
      is certainly of prognostic significance. Studies are ongoing to establish the
      validity of the less-invasive sentinel node biopsy in determining axillary nodal
      status. Perhaps the most significant change in today's approach to breast cancer
      is the reliance on well-controlled prospective studies to evaluate outcome and
      determine the appropriate surgical procedure.

PMID- 14972271
TI  - Intra-abdominal pseudocysts as a complication of ventriculoperitoneal shunts: a
      case report and review of the literature.

PMID- 14972272
TI  - Mucinous cystadenoma of the appendix: diagnosis, surgical management, and follow
      up.
AB  - PURPOSE: To review the diagnostic examination and clinical presentation of
      mucinous cystadenoma of the appendix. METHODS: Case report from experience at an
      Air Force tertiary care hospital in a 66-year-old woman with chronic right lower
      quadrant pain. RESULTS: After extensive preoperative evaluation and subsequent
      diagnostic laparoscopy, a right hemicolectomy was performed for a mucinous
      cystadenoma of the appendix. CONCLUSIONS: Appendiceal mucinous cystadenoma is a
      rare entity found in only 0.3% of appendiceal specimens. Preoperative evaluation
      with radiologic and endoscopic methods is helpful but not always diagnostic.
      Although a benign disease process, complications from rupture, invasion into
      adjacent organs, or recurrence warrant adherence to strict oncologic principles
      for resection.

PMID- 14972273
TI  - Selective arterial embolization for control of lower gastrointestinal bleeding:
      recommendations for a clinical management pathway.
AB  - PURPOSE: Angiography remains as the modality of choice in the diagnosis of lower
      gastrointestinal bleeding. Traditionally, angiography is used for localization of
      a bleeding source for surgical resection. Advances in transcatheter techniques
      have allowed for hemorrhage control through embolization of bleeding points,
      without the need for emergent laparotomy. METHODS: A series of 10 consecutive
      patients who underwent angiographic embolization for lower gastrointestinal
      hemorrhage was retrospectively reviewed. Success and complication rates, as well
      as post-embolization follow-up methods, were recorded. RESULTS: Over a 3-year
      period, 10 angiographic embolizations were performed for lower gastrointestinal
      hemorrhage. Average age of the patients was 75 years. Source of hemorrhage
      included diverticular disease in 4 patients, cancer in 2, polyps in 2,
      angiodysplasia in 1, and anastomotic bleeding in 1. Six patients required no
      further therapy. Four patients went on to have surgery: Three secondary to
      recurrent hemorrhage, 1 due to sepsis from ischemic bowel necrosis. There were no
      deaths. Four patients had an abdominal and pelvic computed tomography (CT) scan
      within 48 hours of embolization. Four patients had a colonoscopy within 48 hours
      of the procedure. CONCLUSIONS: Angiography remains an important diagnostic tool
      in the management of lower gastrointestinal bleeding. In addition, it is a safe
      and effective treatment option, especially in patients with high surgical risk.
      Hemorrhage control obtained in the angiography suite may allow for patient
      stabilization and resuscitation with staging and bowel preparation for surgery.
      Patients need to be carefully monitored for evidence of bowel ischemia through
      the use of colonoscopy or computed tomography.

PMID- 14972274
TI  - Vasovasostomy: multiple children and long-term pregnancy rates.
AB  - PURPOSE: To determine the long-term patency and pregnancy rates after
      vasovasostomy and to determine the likelihood of having more than 1 child after
      this procedure. MATERIALS AND METHODS: We performed a retrospective examination
      of 73 patients that were at least 4 years out from vasovasostomy at our
      institution. Patients and their partners completed questionnaires that focused on
      their pre- and post-procedure fertility, vasal obstructive interval, time to
      pregnancy, and the number of children conceived. All patients were asked to
      obtain a current semen analysis. RESULTS: From a population of 73 patients with
      proven prior fertility, 43 could be contacted for data collection. Of the 43 men,
      39 (91%) reported that they had actively tried to father children. These 39 men
      are a mean of 84.8 months (range, 4 to 10 years) out from their surgery, with a
      mean vasal obstructive interval of 87 months (7.4 years). All men denied using
      assisted reproduction techniques except the father of the only twins, who
      reported the use of ICSI for female-factor infertility. He was excluded from
      further pregnancy calculations. Forty-five percent of couples achieved at least 1
      pregnancy, whereas 6 of 17 (35%) conceived 2 children. Mean time to conception
      was 14.7 months for the first child and 51 months for the second (range, 13 to
      108 months). In those that did not conceive (n = 21), the mean obstructive
      interval was 106 months versus 81 months for those that did conceive. This time
      interval was not statistically different (P > 0.05). Mean maternal age was
      significantly less in those that did versus those that did not conceive (32.2 vs
      36.6 years) (P < 0.01). We also noted that 10 of 21 were with a different spouse
      that had never been pregnant. Three of these 10 had known female-factor fertility
      problems. Semen analyses were obtained in 6 of the 21 patients that did not
      father children. Only 1 of the 6 was azoospermic. Thirteen (33%) desired more
      than 1 child at the time of vasectomy reversal. CONCLUSIONS: After vasovasostomy
      in patients with a vasal obstructive interval of 7 years, up to 45% of couples
      may achieve pregnancy and up to 35% could go on to conceive a second child. Long
      term anastomosis patency after the procedure is estimated to be approximately
      60%. Maternal age is a significant factor in predicting a couple's success in
      conceiving a child. Vasovasostomy remains a highly effective option for
      restoration of fertility in vasectomy patients, while offering the opportunity
      for multiple pregnancies with only a single intervention.

PMID- 14972275
TI  - The inventors of the Swan-Ganz catheter: H. J. C. Swan and William Ganz.

PMID- 14972276
TI  - Complications of combined gastric restrictive and malabsorptive procedures: Part
      1.

PMID- 14972281
TI  - Laparoscopic adrenalectomy: indications and technique.

PMID- 14972282
TI  - Rembrandt's anatomy lesson as a metaphor for education.

PMID- 14972283
TI  - Food for thought: Why physicians should reconsider gifts from pharmaceutical
      companies.

PMID- 14972284
TI  - In vitro fertilization: babies, babies, and more babies.

PMID- 14972285
TI  - Presumed consent for organ transplantation: a better system.

PMID- 14972286
TI  - Race and judgment.

PMID- 14972288
TI  - The other contributions of Alfred Blalock.

PMID- 14972289
TI  - A review of laparoscopy for non-obstetric-related surgery during pregnancy.
AB  - PURPOSE: Similar to the general population, parturients (and their fetuses) could
      benefit from the reduced manipulation associated with laparoscopy. The purpose of
      this article is to review the current state of knowledge (both clinical and
      experimental) with respect to the fetal effects of maternal laparoscopy for non
      obstetric-related surgery during pregnancy. METHODS: Human and experimental
      animal results are examined, and we present preliminary data from our own
      laboratory. CONCLUSIONS: Future experiments are proposed to further develop and
      refine standards of care for general surgeons and obstetricians who are presented
      with gravid females in abdominal distress.

PMID- 14972290
TI  - Transitions.

PMID- 14972291
TI  - Handheld medicine--handheld software to ease the day and improve patient care.

PMID- 14972293
TI  - Acute embolic occlusion of the distal aorta.
AB  - PURPOSE: Acute occlusion of the abdominal aorta requires rapid diagnosis and
      intervention to prevent loss of life or limb. The overall mortality due to
      embolic occlusion is reported to be over 30%. The most common source of emboli is
      the heart, secondary to atrial fibrillation or myocardial infarction. METHODS: A
      patient is herein presented who arrived at the emergency department 6 hours after
      onset of classic signs of acute arterial occlusion. RESULTS: She had a saddle
      embolus of the distal abdominal aorta with extension of the clot into both iliac
      and femoral arteries. CONCLUSIONS: Heparin therapy and embolectomy successfully
      reestablished blood flow. The etiology, presentation and management of aortoiliac
      occlusion is discussed.

PMID- 14972294
TI  - Fractured heterotopic bone in a midline abdominal wound.
AB  - PURPOSE: Heterotopic bone formation, although most often reported after trauma
      and elective joint surgery, can occur in abdominal surgical scars. The lesion may
      not be discovered for a long period of time after it occurs, and the patient,
      except in rare circumstances, is asymptomatic. METHODS: A patient is reported who
      developed heterotopic bone formation in an upper midline incision after a Nissen
      fundoplication with complications. The heterotopic bone became symptomatic after
      it had undergone complete fracture. Symptoms disappeared after the bony mass was
      removed. The English-language literature was reviewed to study the clinical
      significance of heterotopic bone formation, particularly in abdominal wounds.
      RESULTS: Literature reports of heterotopic bone formation in an abdominal wound
      are uncommon, and the etiology remains obscure. Symptoms are unusual and are
      often related to the patient's activity. This case appears to be the only report
      of fracture of heterotopic bone in an abdominal scar. CONCLUSIONS: Heterotopic
      bone formation should be considered when a hard mass develops in an abdominal
      surgical scar. Excision is not indicated unless the patient develops symptoms.

PMID- 14972295
TI  - Hepatic subcapsular biloma: a rare complication of laparoscopic cholecystectomy
      and common bile duct exploration.
AB  - PURPOSE: Description of an unusual complication of laparoscopic cholecystectomy
      and common bile duct exploration. METHODS: Case report from experience at an Air
      Force tertiary care hospital in a 70-year-old woman undergoing laparoscopic
      cholecystectomy. Literature search for journal articles reporting similar
      complications using Medline, PubMed, and Ovid Internet search systems. RESULTS: A
      hepatic subcapsular biloma was diagnosed on postoperative day 11 from an elective
      laparoscopic cholecystectomy and common bile duct exploration. Review of the
      literature found only 2 other reports of this complication. CONCLUSIONS: Hepatic
      subcapsular biloma is a rare complication of laparoscopic cholecystectomy.
      Computed tomography is highly sensitive for diagnosing bilomas, and percutaneous
      drainage procedures are appropriate treatment. Imaging of the biliary tree should
      be performed early to determine the location and extent of bile leaks.

PMID- 14972296
TI  - The spectrum of treatment and future diagnosis of early non-small cell lung
      carcinoma.
AB  - PURPOSE: Review the surgical treatment of 56 patients at a single institution of
      early stage non-small cell lung carcinoma (NSCLC). Briefly review the literature
      to report the current indications for limited pulmonary resection. Discuss newer
      methods of assessing early stage NSCLC. METHODS: We reviewed 56 lobectomies
      performed at the Biloxi Veterans Administration Medical Center from January 1992
      to December 1997 for NSCLC to report the incidence of N1 positive lymph nodes and
      survival data. Additionally, a search of PubMed, Ovid, and MDConsult.com, using
      search parameters of non-small cell lung carcinoma, limited pulmonary resection,
      lobectomy, and comorbidity, were used to determine indications for treating non
      small cell lung carcinoma. RESULTS: N1 positive lymph nodes occurred in 11 out of
      56 patients; 4 were identified preoperatively. In this sample, 21 patients were
      Stage IA, 21 Stage IB, 6 Stage IIA, and 8 Stage IIB, and their 4-year median
      survival was as follows: (IA) greater than 44.80 months, (IB) greater than 48.0
      months, (IIA) greater than 25.28 months, and (IIB) = 11.18 months. Four-year
      survival rates by stage were IA= 10/21 (47.62%), IB= 14/21 (66.67%), IIA= 2/6
      (33.33%), and IIB= 0/8 (0.0%). CONCLUSIONS: The 4-year survival data we reviewed
      were less favorable than is reported by others. Patient medical comorbidity,
      patient age, and sample size are thought to account for this difference.
      According to our literature review, reasons for limited pulmonary resection
      include poor physical performance, marginal lung reserve, synchronous bilateral
      tumors, and superior sulcus tumors (T3) in which the tumor primarily invades the
      chest wall. Heavier consideration of these indications might have improved the
      outcomes seen in this population.

PMID- 14972297
TI  - Assessing educational validity of the Morbidity and Mortality conference: a pilot
      study.
AB  - PURPOSE: To assess inter-rater agreement in perceptions of cases presented during
      Morbidity & Mortality conference (M&M) and changes associated with initiation of
      a modified M&M. METHODS: Faculty, residents, fellows, and students at weekly M&M
      between June 2001 and March 2002 voluntarily completed an anonymous questionnaire
      after each M&M case presentation, which asked: if the complication was avoidable
      (yes/no/not sure), if consensus was reached among participants (yes/no/not sure),
      the primary cause of the complication (diagnostic error, technical error,
      judgment error, nature of disease, other), when the primary cause occurred
      (preoperatively, intraoperatively, postoperatively), and which, if any, of 16
      listed actions could prevent similar future problems. On September 24, 2001, the
      conference was lengthened and modified. Data collected before (n = 30 cases) and
      after M&M modification (n = 46 cases) were compared. RESULTS: A total of 76 cases
      were evaluated for a total of 860 completed forms. In 57 cases (75%), majority
      opinion (ie, > or =50% of participants) indicated that the complication resulted
      from either nature of disease (n = 32, 41%), or error in diagnosis (n = 5, 7%),
      technique (n = 8, 11%) or judgment (n = 12, 17%). There was no clear majority for
      the remainder of the cases. Relative to cases presented prior to M&M
      modification, for those presented post-modification, the majority perceived that
      consensus was reached more often (96% of cases vs. 70% of cases, p<.01), and that
      complications were more often avoidable (54% of cases vs. 23% of cases, p <.05),
      more likely caused during the preoperative period (26% of cases vs. 7% of cases,
      p <.01) and less likely caused during the postoperative period (28% of cases vs.
      67% of cases, p <.01). CONCLUSIONS: The variability in questionnaire responses
      suggests that an evaluation instrument such as that reported here can be useful
      in assessing educational needs, quantifying the efficacy of case presentations,
      and assessing the effects of modifications to conference content and structure.
      Modifying M&M in accordance with published recommendations appears to improve
      case analysis and consensus among participants.

PMID- 14972298
TI  - Factors influencing career choice among medical students interested in surgery.
AB  - PURPOSE: The number of applicants to general surgery programs has recently
      declined. We set out to determine factors that influence career choice among
      medical students. METHODS:  DESIGN: survey; SETTING: university medical center;
      PARTICIPANTS: fourth-year medical students; INTERVENTION: distribution and
      completion of the survey. PARTICIPANTS ranked 18 items coded on a Likert scale
      from 1 (not important) to 8 (very important). These factors were career
      opportunities, academic opportunities, experience on core rotation/subinternship,
      role model(s) in that specialty (mentors), length of training required, lifestyle
      during residency, work hours during residency, ability to obtain residency
      position, concern about loans/debt, call schedule, lifestyle after training, work
      hours after training, financial rewards after training, intellectual challenge,
      patient relationships/interaction, prestige, future patient demographics, and
      gender distribution in the specialty. Students were asked to provide gender,
      career choice, number of programs they applied to, and the number of programs at
      which they were interviewed. RESULTS: A total of 111 of the 160 surveys
      distributed were returned (69%). A total of 48 of the students were men, 31 were
      women, and 32 did not identify their gender. Nineteen students were interested in
      pursuing a career in surgery or a surgical subspecialty. Factors predicting
      surgery as a career choice were career opportunities (p < 0.04) and prestige (p <
      0.003). Lifestyle during residency (p < 0.0007), work hours during residency (p <
      0.008), and quality of patient/physician relationships (p < 0.05) were all
      significantly negatively correlated with the choice of a surgical career.
      Students pursuing a surgical career applied to greater than 31 programs compared
      with 11 to 15 for the nonsurgical students (p < 0.0001). CONCLUSIONS: Prestige
      and career opportunities are more important to students seeking surgical
      residencies. Concerns about lifestyle and work hours during residency and
      perceived quality of patient/physician relationships were deterrents to surgery
      as a career choice. These issues may need to be addressed to increase the number
      of applicants to surgical programs.

PMID- 14972299
TI  - Impaired residents: identification and intervention.
AB  - PURPOSE: To describe the effect of a psychologist on faculty staff supporting
      impaired residents to successful program completion in general surgery. METHODS:
      Since 1996, the Department of Surgery has had a staff psychologist on faculty who
      works closely with the Trauma service. Duties include provision of patient and
      family therapies (representing a revenue-generating activity for the department),
      in-services for staff stress management, research, and community education
      activities. As resident performance issues have arisen, the psychologist has been
      instrumental in early identification of and referral for underlying issues
      affecting resident behavior. RESULTS: From 1996 to October 2001, 12 residents (2
      with multiple referrals) have been identified with significant psychological
      issues impairing performance. The various psychological problems include
      depression, anger control issues, and addictions; required interventions have
      included referrals for therapeutic counseling, recommendations for career change,
      and therapeutic counseling combined with pharmacotherapy. Fellow residents
      referred 4 of the 12 residents to the psychologist for possible evaluation, and
      the remaining 8 had referral initiated by performance concerns. CONCLUSIONS:
      Significant psychological problems can impair resident performance and possible
      training program completion. Early identification and intervention by a
      professional psychologist on faculty can provide support for increased
      opportunity to complete residency training.

PMID- 14972300
TI  - The Leapfrog Initiative: a potential threat to surgical education.
AB  - PURPOSE: The Leapfrog Initiative was established in January 2000 by the Business
      Roundtable (BRT) in response to the Institute of Medicine report on quality and
      safety of medical care. The BRT is composed of chief executive officers of U.S.
      corporations representing more than 28 million employees. Leapfrog has proposed 3
      hospital safety measures-computerized physician order entry, intensive care unit
      physician staffing standards and evidence-based hospital referral, which states
      that hospitals must meet certain volume/year criteria. Three of these criteria
      are pertinent to general surgery. They are abdominal aortic aneurysm (AAA) repair
      greater than or equal to 30/year, carotid endarterectomy (CE) greater than or
      equal to 100/year, and esophageal cancer surgery (ECS) greater than or equal to
      7/year. Hospitals failing to meet these requirements would not be eligible to
      treat patients employed by BRT corporations. METHODS: Data were obtained from the
      Residency Review Committee (RRC) for Surgery Resident Statistics Summary for 1999
      to 2001. Comparisons were made between the numbers of the Leapfrog index cases
      required and the actual number of cases performed by each graduating chief
      resident. Data from the Connecticut Hospital Association (CHA) for fiscal year
      2000 were also analyzed. Outcomes for procedures at The Stamford Hospital were
      reviewed. RESULTS: Data obtained from the RRC reveal that the mode numbers for
      each of the 3 evidence-based standards for each graduating chief resident in 2000
      and 2001 are 5 and 3 for AAA, 15 and 17 for CE, and 0 in both years for ECS.
      Extrapolation using the mode for each procedure reveals that hospitals with 5 or
      6 graduating chief residents may be ineligible to treat patients for AAA and CE.
      Hospitals with less than or equal to 5 chief residents would be excluded from
      performing CE. Very few institutions are performing adequate numbers of ECS. Only
      4 of 31 CT hospitals would be allowed to perform AAA, and only 3 of 31 could
      perform CE. Only 1 Connecticut hospital performed more than 7 ECS cases in FY
      2000. It is apparent that Leapfrog standards will have serious economic impact on
      many hospitals, as well as displacing patients to other cities for care.
      CONCLUSIONS: Surgical chairs and program directors should be aware of the
      Leapfrog standards and assess their own programs and institutions for compliance.
      Performance improvement and outcomes data for all evidence-based standards should
      be reviewed.

PMID- 14972301
TI  - Utilizing community leaders to teach professionalism.

PMID- 14972302
TI  - Juan M. Acosta, MD, PhD: acute pancreatitis and the migration of stones.

PMID- 14972304
TI  - Automatically downloading software patches: what you don't know can and will hurt
      you.

PMID- 14972305
TI  - Complications of gastric restrictive procedures.

PMID- 14972306
TI  - General complications.

PMID- 14972307
TI  - Laparoscopic adjustable gastric banding [Lap-Band].

PMID- 14972308
TI  - Management of complications in vertical banded gastroplasty.

PMID- 14972309
TI  - Laparoscopic vertical banded gastroplasty.

PMID- 14972310
TI  - Gastroesophageal reflux disease: current diagnosis and treatment.

PMID- 14972311
TI  - Laparoscopic fundoplication.

PMID- 14972312
TI  - William E. Ladd: Father of Pediatric Surgery.

PMID- 14972313
TI  - Bowel obstruction caused by a Meckel's diverticulum enterolith: a case report and
      review of the literature.
AB  - Meckel's diverticulum is the most common congenital gastrointestinal anomaly. It
      may infrequently cause bleeding, perforation, or rarely obstruction. Formation of
      enteroliths in the diverticulum is uncommon. We present a case of small bowel
      obstruction from an expelled enterolith.

PMID- 14972315
TI  - Why should the first be last? "seasonal" variations in the National Board of
      Medical Examiners (NBME) Subject Examination Program for medical students in
      surgery.

PMID- 14972314
TI  - Totally extraperitoneal (TEP) approach for inguinal hernia: the favorable
      learning curve for trainees.
AB  - PURPOSE: Endoscopic inguinal herniorrhaphy has become an established approach to
      groin hernia. The use of a totally extraperitoneal (TEP) approach allows a
      tension-free, preperitoneal approach with potentially less discomfort and
      morbidity than do classic repairs. Concerns have been raised regarding excessive
      cost, need for general anesthesia, and an extensive learning curve for surgeon
      and resident trainee alike. METHODS: A retrospective analysis of 264 consecutive
      patients undergoing TEP for inguinal hernia repair from September 1995 to April
      2000 was performed. All repairs were performed by surgical trainees under the
      supervision of a single staff surgeon. RESULTS: Mean age of 256 men and 8 women
      undergoing 386 inguinal hernia repairs was 54 years (range, 15-86). Inguinal
      hernias were unilateral (n = 142) or bilateral (n = 122); indirect (52%), direct
      (33%), or pantaloon (15%); 37 defects (10%) were recurrent. Surgical residents (n
      = 74) participated in all 264 operations and were considered the "junior surgeon"
      in 211 cases: 19 chief residents did 35 operations, 9 PG-4s performed 27, 8 PG-3s
      did 17, 10 PG-2s completed 41, and 28 interns did 91 procedures. Mean operative
      time was 96 minutes (range, 30-261) with no statistical difference among PG-1s,
      2s, 3s, 4s, or chief residents learning the procedure. Early postoperative
      complications included urinary retention (n = 25), seroma (n = 3), ileus (n = 3),
      and subcutaneous wound infection (n = 1). Fully 24% of patients desired or
      required overnight admission. All patients (100%) operated on for recurrence (n =
      37) or a previous contralateral repair (n = 19) favored the current TEP approach
      over their prior repair. Hernia recurrence has developed in 8 patients, with 6
      (75%) occurring within the first 40 study patients. Mean follow-up was 3.5 years
      (range, 1.2-5.9 years). CONCLUSIONS: The totally extraperitoneal approach is a
      safe and effective method of inguinal hernia repair. Following a learning curve
      of 40 patients for the staff surgeon, the recurrence rate has been less than 1%,
      with surgical trainees safely performing TEP repairs under supervision.

PMID- 14972316
TI  - Creating a life? Fertility and postgraduate medical education.

PMID- 14972317
TI  - Which handheld should I buy?
AB  - The PDA or handheld computer, is not just a toy of the Cusper generation or for
      your pre-teens to use for games. It is a serious tool that has found a niche in
      medicine. Everyone of our residents carries a PDA and uses it several times a
      day. Web-based programs such as ePocrates provide them with instantaneous
      information on correct drug dosage and interactions. The literature already
      contains reports of the ability of this type of PDA-based software to reduce
      prescription errors. Our residents also use shareware versions of patient
      management software to keep track of patients on service and of individual
      surgeon's preferences. If your residents use ResSOLution to enter surgery case
      data, they will find that the new, PDA-based version shown at the recent Surgical
      Education Week will make data entry and transmission to the program director's
      files a piece of cake. The software has a long-awaited, full alpha-search
      capability for current CPT codes. I download my calendar and telephone files to
      my PDA every day so that I have everything on my office computer in the "palm" of
      my hand where and when I need it. Try remembering the office number of a
      referring physician in the middle of the night or suffering through the Muzak
      ridden delays of waiting for a hospital operator to give you a specific extension
      and you will carry your PDA too!

PMID- 14972318
TI  - Statistics in the computer age: part 1.

PMID- 14972319
TI  - Presidential address: program director--what kind of job is that?

PMID- 14972320
TI  - An internet-based residency assessment application that fulfills the outcome
      project's requirements.
AB  - PURPOSE: The acquisition and organization of information about surgical resident
      performance, as well as the assessment of the educational value of different
      rotations, is cumbersome and time consuming. The additional requirement by the
      Accreditation Council of Graduate Medical Education (ACGME) to assess General
      Competencies in the Outcome Project has multiplied the paperwork and workload
      demanded from each program director and residency coordinator. The purpose of our
      study was to simplify the collection of information and to organize it in a way
      that would fulfill the requirements of the Outcome Project. METHODS: We developed
      an Internet-based application for maintaining a database of residents, faculty,
      rotations, and their evaluations. RESULTS: The modular design allows flexibility
      in the selection of different tools that can be added at the discretion of the
      program director. The use of this application has facilitated the assessment
      process. Evaluations are instantly available for review. CONCLUSIONS: The General
      Competencies of any resident can be easily demonstrated, compared, and presented
      in an organized fashion that allows quick reaction to problems and facilitates
      compliance with the Outcome Project with little additional work for the residency
      staff.

PMID- 14972321
TI  - Spectrum of general surgery in rural Iowa.
AB  - PURPOSE: One-quarter of the United States of America's population lives in rural
      areas, but only 12.3% of physicians live and work in rural areas. Nearly one
      quarter of the counties in Iowa boast a patient-to-physician ratio of 3000:1. The
      number of rural surgeons is decreasing, and current residency programs may not
      optimally train graduates for the spectrum of surgical practice seen in rural
      areas. The scope of surgical practice differs between rural and non-rural
      surgeons, and in this study, we identified the types of surgery performed by 6
      rural Iowa surgeons and compared the practices of rural and non-rural surgeons in
      Iowa. METHODS: Data from personal interviews and questionnaires with rural Iowa
      general surgeons and rural Iowa hospital administrators and results from the Iowa
      General Surgeon Practice Opportunity Survey were analyzed retrospectively.
      RESULTS: In 1995, 31 general surgeons were recruiting a general surgeon partner,
      of which 25 were in rural Iowa communities. Eighteen rural Iowa Hospital
      administrators were actively recruiting a general surgeon during the same time
      period. In September 2000, many of these positions remained unfilled. A total of
      4963 surgical procedures were performed by 6 rural Iowa general surgeons in Iowa
      in 1995. Endoscopic, alimentary, and obstetrics and gynecologic procedures were
      the most frequently performed. Excluding endoscopy, 26% of all procedures
      performed were procedures not among the Accreditation Council of Graduate Medial
      Education (ACGME) list of requirements for graduating surgical residents.
      CONCLUSIONS: Rural Iowa general surgeons perform a large volume of surgery and
      more subspecialty procedures than do their non-rural counterparts. Surgical
      residency programs need to more adequately train residents interested in rural
      general surgery in an effort to increase the pool of graduating surgical
      residents trained to deal with the scope of procedures a rural practice offers.
      This will help reduce the shortage of rural general surgeons in the United States
      of America.

PMID- 14972322
TI  - The development of new medical specialties.

PMID- 14972324
TI  - Mechanisms of genetic susceptibility to type I diabetes: beyond HLA.
AB  - An individual's predisposition to Type I diabetes (T1D) is largely determined by
      complex interactions between several genetic loci and other, nonheritable
      factors. In T1D, the HLA locus has been known for decades to contribute 50% of
      the inherited risk. Outside the HLA are many proposed candidate loci with smaller
      effects, but only two confirmed candidate genes, the INS-VNTR and the CTLA-4
      genes, which together do not contribute more than 15% of the risk. Because of the
      high frequency of the disease-associated DNA variants of these genes,
      understanding the biological mechanisms of such DNA variation in the context of
      T1D can have tremendous impact on the development of preventive therapeutics.
      However, establishing a causal relationship between common DNA variations and
      disease-predisposing functional effects is not trivial and remains difficult, as
      the effects are expected to be subtle. The variable-number tandem-repeat (VNTR)
      region upstream of the insulin gene is known to mediate expression in the thymus
      and pancreas, whereas various polymorphisms in the 5' and 3' regulatory regions
      of CTLA-4 are thought to alter gene expression and a coding A49G polymorphism
      exerts effects on post-translational processing. This review details the latest
      efforts in elucidating the functional mechanisms that explain the genetic
      association of the INS-VNTR and CTLA-4 genes with T1D.

PMID- 14972325
TI  - Hypoglycosylation of alpha-dystroglycan in patients with hereditary IBM due to
      GNE mutations.
AB  - Hereditary inclusion body myopathy (HIBM) is an adult onset neuromuscular
      disorder associated with mutations in the gene UDP-N-acetylglucosamine-2
      epimerase/N-acetylmannosamine kinase (GNE), whose product is the rate limiting bi
      functional enzyme catalyzing the first two steps of sialic acid biosynthesis.
      Loss of GNE activity in HIBM is thought to impair sialic acid production and
      interfere with proper sialylation of glycoconjugates, but it remains unclear how
      such a defect would lead to muscle destruction and muscle weakness.
      Hypoglycosylation of alpha-dystroglycan, a central protein of the skeletal muscle
      dystrophin-glycoprotein complex, results in disturbed interactions with
      extracellular matrix proteins. This has recently been identified as the
      pathomechanism involved in several congenital muscular dystrophies. We examined
      the glycosylation status of alpha-dystroglycan in muscle biopsies of four HIBM
      patients of non-Iranian Jewish origin (one American, two Indians, and one Greek).
      Two of these patients carry novel compound heterozygous GNE mutations on exon 2
      and exon 9. All four muscle biopsies showed absent or markedly reduced
      immunolabeling with two different antibodies (VIA4 and IIH6) to glycosylated
      epitopes of alpha-dystroglycan. Normal labeling was found using antibodies to the
      core alpha-dystroglycan protein, beta-dystroglycan, and laminin alpha-2. These
      findings resemble those found for other congenital muscular dystrophies,
      suggesting that HIBM may be a "dystroglycanopathy," and providing an explanation
      for the muscle weakness of patients with GNE mutations.

PMID- 14972326
TI  - Glycogenosis type II: identification and expression of three novel mutations in
      the acid alpha-glucosidase gene causing the infantile form of the disease.
AB  - Glycogenosis type II (GSDII) is an autosomal recessive disorder due to the
      deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). We identified
      three novel point mutations, C399A, T1064C, and C2104T, in three unrelated
      Italian patients with the infantile form of the disease. The C399A mutation was
      present in homozygosity in proband 1. The C >A transition introduces a premature
      stop signal in exon 2 resulting in no enzyme production that is correlated with
      the severe clinical phenotype in this patient. The other two nucleotide changes
      were missense mutations. The T1064C mutation, which changes Leu in position 355
      into Pro, was carried in homozygosity by proband 2. The C2104T nucleotide change,
      which substitutes Arg 702 into Cys, was present in proband 3 in combination with
      a known severe mutation DeltaI17-18. The in vitro expression in COS-1 cells of
      T1064C and C2104T constructs demonstrated no enzymatic activity with respect to
      the negative control cells. Western blot analysis revealed that both T1064C and
      C2104T mutant proteins produced in COS-1 cells migrated in SDS-PAGE as the GAA
      inactive precursor of 110kDa. Immunofluorescence detection of mutant alpha
      glucosidases showed enzyme localization primarily in the ER-Golgi compartment,
      suggesting that T1064C and C2104T mutations could affect the normal processing
      and stability of the enzyme. In vitro studies demonstrated that the same degree
      of deficiency in T1064C and C2104T mutations, which is in contrast with patient
      phenotype. A better correlation was observed with the in vivo studies since
      proband 2, with a less severe phenotype, presented with low residual enzyme
      activity while in proband 3, with a classic severe infantile onset GSDII,
      fibroblast enzyme activity was completely absent.

PMID- 14972327
TI  - Characterization of cystathionine beta-synthase gene mutations in homocystinuric
      Venezuelan patients: identification of one novel mutation in exon 6.
AB  - This study describes for the first time the cystathionine beta-synthase (CBS)
      gene mutations in Venezuelan patients. A total of five disease-causing mutations
      were identified in 9 out of 10 independent chromosomes. Four of the mutations
      have been previously described (G85R, T191M, D234N, and D444N) and a novel
      mutation was found (Q243X). Two common polymorphisms (699C/T and 1080C/T) were
      found in the CBS gene. Mutation analysis was performed using a combined screening
      approach for CBS mutations: restriction analysis, single-strand conformational
      polymorphism (SSCP) scanning, and sequencing. All the mutations were detected in
      homozygous state, except for Q243X, detected in three heterozygous siblings. Each
      one of the patients studied presented a different mutation. All mutations and
      polymorphisms detected involved hypermutable CpG sites, except for the novel
      mutation Q243X. The most common mutations I278T and G307S were not found in any
      of the patients. The CBS mutations present in each country differ from each other
      depending on the demographic profile; therefore, specific mutations scanning must
      be performed in each population for diagnosis and prognosis purposes.

PMID- 14972328
TI  - Human mevalonate pyrophosphate decarboxylase is localized in the cytosol.
AB  - In the past decade several reports have claimed that peroxisomes play a critical
      role in the isoprenoid/cholesterol biosynthetic pathway based on the finding of a
      predominant peroxisomal localization of several of the enzymes involved. Other
      reports, however, do not support the peroxisomal localization of these enzymes.
      In this study we have studied the subcellular localization of one of the enzymes,
      human mevalonate pyrophosphate decarboxylase, by conventional subcellular
      fractionation and digitonin permeabilization studies, immunofluorescence
      microscopy, and immunoelectron microscopy. We found a cytosolic localization for
      both endogenous human mevalonate pyrophosphate decarboxylase (in human
      fibroblasts, liver, CV1 and HEK293 cells) and overexpressed mevalonate
      pyrophosphate decarboxylase (in human fibroblasts, HEK293 and CV1 cells) but no
      indication for a peroxisomal localization. Our results do not support a central
      role of peroxisomes in the isoprenoid/cholesterol biosynthetic pathway.

PMID- 14972329
TI  - Human recombinant mutated forms of the mitochondrial COX assembly Sco2 protein
      differ from wild-type in physical state and copper binding capacity.
AB  - The human Sco2 protein is a cytochrome c oxidase assembly protein that
      participates in mitochondrial copper pathway, acting downstream of Cox17 protein.
      In a previous work, we detected mutations in the human SCO2 gene in three
      unrelated infants with fatal cardioencephalomyopathy and COX deficiency. In this
      study, full-length processed recombinant wild-type and two mutated forms of
      hSco2p (w/t-rhSco2p, E140K-rhSco2p, and S225F-rhSco2p) were produced in bacteria
      as soluble recombinant peptides for the first time and evaluated for differences
      in their physical state and ability to bind copper. Our data indicate the
      following: (a) w/t-rhSco2p and S225F-rhSco2p were found to be in a monomeric form
      in contrast to E140K-rhSco2p that was in a major non-reducible dimer and a minor
      monomer form; (b) wild-type and mutated rhSco2p exhibited clear differences in
      their physical conformational state, as shown by circular dichroism and thermal
      denaturation analyses; (c) copper binding studies showed that E140K-rhSco2p bound
      markedly less copper while S225F-rhSco2p more than expected as compared to amount
      of the copper bound with w/t-rhSco2p. rhCox17p served as positive control
      experiment. These data indicate that S225F and E140K mutations found in the SCO2
      gene derived from patients alter the physical conformational state of encoded
      hSco2p that may disturb the normal copper transport pathway in mitochondria.
      These findings are valuable for understanding the molecular basis of fatal
      cardioencephalomyopathy and COX deficiency and for designing appropriate
      pharmacological interventions.

PMID- 14972330
TI  - A high throughput beta-globin genotyping method by multiplexed melting
      temperature analysis.
AB  - For a population-based newborn screening program, challenges exist in using
      technological advances to improve the quality and efficiency of the existing
      screening program and to develop new diagnostic capabilities. A newly developed
      genotyping method for screening of common mutations within the beta-globin gene
      is described here. This genotyping system consists of three major components: an
      automation system for high throughput DNA extraction and PCR setup, a
      conventional thermal cycler, and a LightTyper instrument for post-PCR melting
      temperature analysis. Briefly, genomic DNA is extracted from dried blood on a
      filter paper using methanol and Tris buffer. Genetic fragments of interest are
      amplified by asymmetric PCR. Fluorescent labeled probes are added during PCR
      setup, which eliminates the need for any post-PCR sample handling process.
      Melting temperature analysis is achieved through fluorescent resonance energy
      transfer (FRET) reaction using the LightTyper instrument. The assay is designed
      to simultaneously detect three common beta-globin mutations, S(A173T), C(G172A),
      and E(G232A), and can identify any of the eight possible genotypes in a single
      reaction: AA, AE, EE, AS, SC, SS, AC, and CC (A represents wild type allele). The
      method was validated with a large number of samples in both a retrospective and
      parallel study. Results were compared to those obtained by isoelectric focusing
      electrophoresis. The accuracy of this genotyping method is greater than 99%.

PMID- 14972331
TI  - Modulation of mitochondrial aconitase on the bioenergy of human prostate
      carcinoma cells.
AB  - A bioenergetic theory of prostate malignancy proposed that normal citrate
      producing prostate epithelial cell become citrate-oxidizing cells, in which
      mitochondrial aconitase (mACON) is not limiting, providing the energy required
      for the onset and progression of malignancy and metastasis. However, no direct
      evidence has been approved to support the hypothesis. A full-length cDNA encoding
      human skeletal muscle mACON cDNA was cloned and sequenced. mACON cDNA contains 19
      bp 5' untranslated region, a 2343-bp coding segment, and 376-bp 3' untranslated
      region. This precursor enzyme contains mitochondrial targeting sequence of 27
      amino acid residues and mature enzyme of 753 amino acids residues. A human anti
      mACON overexpression vector containing the 1171-bp mACON cDNA fragment in the
      reverse orientation was stable transfected into human prostate carcinoma cells,
      PC-3 and DU145 cells. Results showed that mACON antisense blocked 40-60% mACON
      expression and enzymatic activity which induced decrease in the intracellular ATP
      biosynthesis but increase citrate secretion in the human prostate carcinoma
      cells. mACON antisense-transfected cells have lower cell proliferation ratio than
      the mock of DNA-transfected cells. Our study demonstrated the key role of the
      mACON in the cellular bioenergy and cell proliferation of human prostate
      carcinoma cells.

PMID- 14972332
TI  - Another aspect of the galactosemia enigma.

PMID- 14972335
TI  - Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in
      osteoarthritis.
AB  - OBJECTIVES: To describe a semi-quantitative scoring method for multi-feature,
      whole-organ evaluation of the knee in osteoarthritis (OA) based on magnetic
      resonance imaging (MRI) findings. To determine the inter-observer agreement of
      this scoring method. To examine associations among the features included in the
      scoring method. METHODS: Nineteen knees of 19 patients with knee OA were imaged
      with MRI using conventional pulse sequences and a clinical 1.5 T MRI system.
      Images were independently analyzed by two musculoskeletal radiologists using a
      whole-organ MRI scoring method (WORMS) that incorporated 14 features: articular
      cartilage integrity, subarticular bone marrow abnormality, subarticular cysts,
      subarticular bone attrition, marginal osteophytes, medial and lateral meniscal
      integrity, anterior and posterior cruciate ligament integrity, medial and lateral
      collateral ligament integrity, synovitis/effusion, intraarticular loose bodies,
      and periarticular cysts/bursitis. Intraclass correlation coefficients (ICC) were
      determined for each feature as a measure of inter-observer agreement.
      Associations among the scores for different features were expressed as Spearman
      Rho. RESULTS: All knees showed structural abnormalities with MRI. Cartilage loss
      and osteophytes were the most prevalent features (98% and 92%, respectively). One
      of the least common features was ligament abnormality (8%). Inter-observer
      agreement for WORMS scores was high (most ICC values were >0.80). The individual
      features showed strong inter-associations. CONCLUSION: The WORMS method described
      in this report provides multi-feature, whole-organ assessment of the knee in OA
      using conventional MR images, and shows high inter-observer agreement among
      trained readers. This method may be useful in epidemiological studies and
      clinical trials of OA.

PMID- 14972336
TI  - T2 mapping: an efficient MR quantitative technique to evaluate spontaneous
      cartilage repair in rat patella.
AB  - OBJECTIVE: To evaluate the ability of T2 mapping on an 8.5 T imager to
      characterize morphologically and quantitatively spontaneous repair of rat
      patellar cartilage following full thickness defect. METHODS: Patellar cartilage
      defects were created in 24 rats knees on D0. Eight rats per time-point were
      killed on D20, D40 and D60 after surgery. T2 maps of repair tissue in patellar
      defects were obtained from eight different axial spin echo images on an 8.5 T
      imager. Global, superficial and deep T2 values were evaluated in spontaneous
      repair tissues (3x8 right patellae) vs the opposite patellae (3x8 left patellae)
      of the same animals. MR data were compared with macroscopic and histological
      studies. RESULTS: T2 map was able to identify morphologically three types of
      repair tissue observed macroscopically and histologically: 'total', 'partial' and
      'hypertrophic' repair tissue. 'Total' and 'partial' repair tissues were
      characterized by global T2 values almost similar to controls, whereas
      'hypertrophic' repair tissues were characterized by T2 global values higher than
      controls. Zonal variation between superficial and deep T2 values observed in
      controls was not depicted in repair tissue before D60. CONCLUSION: T2 map is able
      to characterize quantitatively and qualitatively rat patellar cartilage repair,
      and thus can be promoted, as a non invasive technique, in clinical longitudinal
      studies of articular cartilage repair.

PMID- 14972337
TI  - The use of photooxidized, mushroom-structured osteochondral grafts for cartilage
      resurfacing--a comparison to photooxidized cylindrical grafts in an experimental
      study in sheep.
AB  - OBJECTIVE: This article addresses the problem of structural design with
      osteochondral grafts used for cartilage resurfacing. METHODS: Photooxidized
      cylindrical or mushroom-shaped grafts were surgically implanted in the weight
      bearing area of the medial and lateral femoral condyles of eight sheep (condyles:
      N=8/group). Both types of photooxidized grafts contained no viable chondrocytes
      at the time of implantation. Results were evaluated at 2 and 6 months after
      surgical implantation of the grafts. Qualitative and quantitative evaluation of
      the subchondral bone area was performed using plastic embedded sections of non
      decalcified bone and cartilage specimens and placing emphasis on graft anchorage,
      cyst-like lesions at the base of the cartilage junction and at the base of the
      graft in the subchondral bone region. Cartilage morphology was studied
      qualitatively focusing on viability of the graft and adjacent host cartilage,
      while a score system was developed for semi-quantitative evaluation of the
      overall articular cartilage performance. The semiquantitative scores and
      histomorphometrical measurements were subjected to statistical analysis using a
      factorial analysis of variance (ANOVA-test). RESULTS: The photooxidized mushroom
      shaped grafts developed less fibrous tissue and cyst-like lesions in the
      subchondral bone area at 2 and 6 months compared to the cylindrical grafts. Areas
      of endochondral ossification and bone remodeling were noticeable in the mushroom
      structured grafts at 2 months, and also bone remodeling was more complete at 6
      months than with the cylindrical grafts. Increased numbers of cells were seen in
      the basal remodeling zones of both graft types increased from the 2 months to the
      6 months specimens, but mushroom structured grafts showed better results. In both
      graft types, however, the midzone of the cartilage matrix was still acellular at
      6 months. Cells from the subchondral bone area started to penetrate the calcified
      cartilage zone and tide mark at 2 months and repopulated the old photooxidized
      cartilage matrix already at 6 months after implantation. Cartilage repopulation
      was dependent on a stable subchondral bone area in both types of grafts. Matrix
      degradation of the adjacent host cartilage was minimal at 2 and 6 months. At 6
      months a junction between host and graft cartilage was already noticed in some of
      the mushroom-shaped grafts. CONCLUSION: This study confirmed the importance of
      the subchondral bone area for osteochondral graft survival. In addition it
      demonstrated that the structure of the graft influences considerably the
      architecture of the subchondral bone, and with this the possibility for the
      repopulation of the old cartilage matrix including the junction between the host
      and graft cartilage matrix.

PMID- 14972338
TI  - Adenovirus-mediated gene transfer of glutamine: fructose-6-phosphate
      amidotransferase antagonizes the effects of interleukin-1beta on rat
      chondrocytes.
AB  - OBJECTIVE: To determine whether overexpression of glutamine: fructose-6-phosphate
      amidotransferase (GFAT) in synoviocytes will antagonize the response to
      interleukin-1beta (IL-1beta) of chondrocytes and synovial fibroblasts in co
      culture. METHODS: Synovial fibroblasts from the rat were transduced by an
      adenovirus carrying the cDNA for GFAT and then co-cultured with rat chondrocytes
      encapsulated in alginate beads. Following challenge with 1, 5, or 10 ng/ml of IL
      1beta for 24 h, proteoglycan synthesis by the chondrocytes was determined by
      incorporation of Na2(35)SO4. Production of nitric oxide (NO) and prostaglandin E2
      (PGE2) were monitored by assay of conditioned medium from the co-culture.
      RESULTS: IL-1beta treatment of untransduced-synoviocyte/chondrocyte co-cultures
      resulted in markedly decreased proteoglycan synthesis by the chondrocytes, and
      increased NO and PGE2 levels in the culture medium. In contrast, adenovirus
      mediated transfer of GFAT in synoviocytes prevented both the decrease in
      chondrocyte proteoglycan synthesis and increases in NO and PGE2 provoked by IL
      1beta. CONCLUSIONS: Our study suggests that in a synoviocyte/chondrocyte co
      culture system, overexpression of GFAT by synoviocytes significantly inhibits
      subsequent stimulation by IL-1beta in vitro. Since GFAT is the rate limiting
      enzyme in the synthesis of intracellular glucosamine and its derivatives, these
      results may open new possibilities for osteoarthritis treatment.

PMID- 14972339
TI  - Relative efficiency and validity properties of a visual analogue vs a categorical
      scaled version of the Western Ontario and McMaster Universities Osteoarthritis
      (WOMAC) Index: Spanish versions.
AB  - OBJECTIVE: To compare the performance of visual analogue (VAS) vs categorical
      (CT) scaled versions of the three subscales (pain, stiffness and difficulty) of
      the WOMAC Index in patients with knee osteoarthritis. MATERIAL AND METHODS:
      Patients with knee OA (at least grade II of Kellgren & Lawrence classification)
      were treated for a 6-weeks period with an NSAID. The following measures were
      applied at baseline and after treatment: VAS and CT WOMAC scales, Lequesne Index,
      pain on VAS, and global assessment by patient and observer. Construct Validity
      was determined by correlation of each of the subscale scores with the other
      outcomes both at baseline and after treatment (Pearson's test); responsiveness
      comparing baseline vs final status by Wilcoxon's test; reliability by analysis of
      the internal consistency using Cronbach's alpha at baseline and after the
      treatment period; and test-retest reliability by Kendall's Tau-c statistics.
      Finally, correlation and analysis of the relative efficiency (RE) between the
      subscales of both formats were tested. RESULTS: Seventy-three (8 men and 65
      women) patients with a mean disease duration from first diagnosis of 69 months (3
      to 254) completed the study. The following were the observed values for the
      instruments' psychometric properties: (1) construct validity: correlations ranged
      from 0.30 to 0.84 for VAS and 0.27 to 0.77 for CT subscales; (2) responsiveness:
      achieved P values for the pain, stiffness and difficulty scales were P<0.0001,
      P=0.002 and P<0.0001 in VAS and P=0.003, P<0.0001 and P=0.001 in CT format
      respectively; (3) internal consistency: the obtained Cronbach's alpha
      coefficients ranged from 0.71 to 0.97 for the VAS and 0.64 to 0.95 for the CT
      subscales; (4) test-retest reliability: correlation coefficients ranged from 0.36
      to 0.76 for VAS and 0.34 to 0.52 for CT subscales; and (5) the relative
      efficiency of the subscales in VAS vs CT format were 2.20, 0.91 and 1.91 for
      pain, stiffness and difficulty respectively. Significant correlations between
      subscales in both formats ranging from 0.72 to 0.86 were observed. CONCLUSION: We
      have shown that both the VAS version of WOMAC have adequate evaluative and
      discriminative properties. We found the pain and physical function scales in VAS
      format and the stiffness scale in CT format to have a slightly better performance
      in this sample.

PMID- 14972340
TI  - Intra-articular hyaluronate in experimental rabbit osteoarthritis can prevent
      changes in cartilage proteoglycan content.
AB  - OBJECTIVE: The purpose of this study was to determine the effects of intra
      articular injections of high molecular weight (2000 kDa) sodium hyaluronate (HA)
      on the progression of articular cartilage degeneration in a rabbit partial medial
      meniscectomy model of osteoarthritis. DESIGN: Six experimental groups included
      normal, sham operated, and operated and injected animals, the latter injected
      once-weekly (for two weeks or twelve weeks, beginning four weeks after surgery)
      with either 1% (w/v) HA or phosphate buffered saline (PBS). Following assessment
      of gross morphology, serial adjacent blocks of full-depth articular cartilage
      were prepared from the tibial condyle for analysis of total water,
      hydroxyproline, DNA and proteoglycan (uronic acid) content, as well as the ratio
      of galactosamine to glucosamine. Samples were sub-divided into inner (medial) and
      outer (lateral) regions. RESULTS: No morphological differences were recognized
      between joints injected with PBS and those receiving HA. When analysed
      biochemically, there were no significant differences in hydration, hydroxyproline
      or DNA content between the experimental groups. In contrast, HA injection did
      affect changes in proteoglycan content. Expressed per tissue dry weight, uronic
      acid content in the operated group injected with PBS for two weeks was lower than
      normal (P<0.02), a result not seen in the corresponding HA injected group. After
      12 weeks of PBS injections, uronic acid content (per dry weight) was higher than
      normal (P<0.01), an effect again not observed in the corresponding HA injected
      group. Results for the galactosamine: glucosamine ratio showed a reduction after
      12 weeks of injections, but no differences between PBS and HA injected groups.
      CONCLUSIONS: Once-weekly, intra-articular injection of high molecular weight HA
      can prevent changes in proteoglycan content in tibial condylar articular
      cartilage, compared to PBS injected controls, in the rabbit partial meniscectomy
      model of osteoarthritis.

PMID- 14972341
TI  - Early diagnosis of osteoarthritis using cathepsin B sensitive near-infrared
      fluorescent probes.
AB  - OBJECTIVE: Osteoarthritis is currently diagnosed utilizing X-ray and MRI
      techniques, both of which are based on the morphological changes of tissue.
      However, once changes are detected, the tissue has an irreversible defect. This
      study investigates early diagnosis of OA on a molecular basis using a recently
      developed cathepsin B sensitive near-infrared (NIR) fluorescent probe. METHOD:
      Twelve male nude mice were induced osteoarthritis by intra-articular injection of
      collagenase (1.0%, w/v) into the right knee joint. The left knee joint served as
      the negative control. The cathepsin B NIR probe is activated by arthritis
      associated cathepsin B, thus resulting in the emission of an intensive NIR
      fluorescence signal which can be detected in vivo. NIR fluorescence signals were
      acquired on an optical imaging system using an excitation wavelength of 610-650
      nm and an emission wavelength of 680-720 nm. RESULTS: Mild to moderate
      degenerative cartilage was observed 1 month after collagenase injection. NIR
      fluorescence imaging of mice showed approximately a 3-fold difference in signal
      intensity between osteoarthritic and normal joints 24 h after intravenous
      injection of the reporter probe. Immunohistochemical evaluation also revealed
      cathepsin B expression in the arthritic lesion of femorotibial joints, and not in
      the control contra-lateral knee joints. CONCLUSION: As the cathepsin B
      activatable NIR fluorescent imaging showed a significant difference between the
      osteoarthritic and normal joints, the cathepsin B activatable NIR fluorescent
      probe thus offers a potential new imaging technology for early OA diagnosis.

PMID- 14972342
TI  - Ultrastructural quantification of cell death after injurious compression of
      bovine calf articular cartilage.
AB  - OBJECTIVE: It has been suggested that chondrocyte death by apoptosis may play a
      role in the pathogenesis of cartilage destruction in osteoarthritis, but the
      results of in-vivo and in-vitro investigations have been conflicting. To
      investigate further the cell death in our in-vitro model for traumatic joint
      injury, we performed a quantitative analysis by electron microscopy (EM) of cell
      morphology after injurious compression. For comparison, the TUNEL assay was also
      performed. DESIGN: Articular cartilage explant disks were harvested from newborn
      calf femoropatellar groove. The disks were subjected to injurious compression
      (50% strain at a strain rate of 100%/s), incubated for 3 days, and then fixed for
      quantitative morphological analysis. RESULTS: By TUNEL, the cell apoptosis rate
      increased from 7 +/- 2% in unloaded controls to 33 +/- 6% after injury (P=0.01;
      N=8 animals). By EM, the apoptosis rate increased from 5 +/- 1% in unloaded
      controls to 62 +/- 10% in injured cartilage (P=0.02, N=5 animals). Analysis by EM
      also identified that of the dead cells in injured disks, 97% were apoptotic by
      morphology. CONCLUSIONS: These results confirm a significant increase in cell
      death after injurious compression and suggest that most cell death observed here
      was by an apoptotic process.

PMID- 14972343
TI  - Lidocaine patch 5% improves pain, stiffness, and physical function in
      osteoarthritis pain patients. A prospective, multicenter, open-label
      effectiveness trial.

PMID- 14972344
TI  - A new computer-assisted method for measuring the tibio-femoral angle in patients
      with osteoarthritis of the knee.
AB  - OBJECTIVE: The purpose of this study was to evaluate the inter- and intraobserver
      variability in measuring the tibio-femoral angle using our new computer-assisted
      method, and to compare it with a conventional manual method. METHODS: Radiography
      of all patients of osteoarthritis of the knee in outpatient were performed with
      standing on both legs, and with conventional antero-posterior weight bearing view
      of the knee fully extended. Three examiners measured the tibio-femoral angle with
      the computerized method in 52 subjects with osteoarthritis (73 knees). The tibio
      femoral angle was measured using a computer-assisted method in which the observer
      must visually determine and select eight points on the margins of the femur and
      tibia on a radiographic image displayed on a computer monitor. The inter- and
      intraobserver Intra-class correlation (ICC) was analyzed. RESULTS: The
      interobserver mean correlation of computer-assisted method was 0.970 with a mean
      difference of 0.38 degrees (S.D. 1.125 degrees). The intraobserver mean ICC of
      computer-assisted method was 0.973, with a mean difference of 0.16 degrees (S.D.
      1.12 degrees). An analysis of the difference between conventional methods and our
      new system showed a mean ICC of 0.922, with an intersystem mean difference of
      0.295 degrees (S.D. 1.82 degrees). CONCLUSION: Our computer-assisted method of
      measuring the tibio-femoral angle was simple, easy, and quick, and should be
      considered as an alternate method for measurement.

PMID- 14972346
TI  - Folate, homocysteine, endothelial function and cardiovascular disease.
AB  - Evidence reported from numerous clinical studies over the past decade has
      revealed an association between increased plasma total homocysteine (tHcy)
      concentrations and cardiovascular disease (CVD). In addition, epidemiological
      studies have identified an inverse association between blood folate
      concentrations, folate intake and cardiovascular endpoints, that are independent
      of homocysteine. Folic acid supplementation can lower plasma tHcy concentrations
      safely and inexpensively. Furthermore, folic acid can reverse endothelial
      dysfunction observed in patients with CVD. This reversal in endothelial
      dysfunction with folic acid has been shown to be independent of plasma tHcy
      lowering, suggesting that folate has pleiotropic effects on the vasculature other
      than homocysteine lowering. In vitro evidence demonstrates that 5
      methyltetrahydrofolate (5MeTHF) the main circulating metabolite of folate, can
      increase nitric oxide production and can directly scavenge superoxide radicals.
      The potential beneficial role of folic acid supplements on vascular disease are
      currently being tested in randomized placebo controlled studies.

PMID- 14972347
TI  - Opposite effect of methionine-supplemented diet, a model of hyperhomocysteinemia,
      on plasma and liver antioxidant status in normotensive and spontaneously
      hypertensive rats.
AB  - Hyperhomocysteinemia is often associated with an increase in blood pressure.
      However our previous study has shown that methionine supplementation induced an
      increase in blood pressure in Wistar-Kyoto (WKY) rats and a decrease in blood
      pressure in spontaneously hypertensive rats (SHR) with significant differences in
      plasma homocysteine (Hcy) metabolites levels. Previously liver antioxidant status
      has been shown to be decreased in SHR compared to WKY rats. It has been suggested
      that oxidative stress may predispose to a decrease in NO bioavailability and
      induce the flux of Hcy through the liver transsulfuration pathway. Thus the aim
      of this study was 1) to investigate the effect of methionine supplementation on
      NO-derived metabolites in plasma and urine 2) to investigate whether
      abnormalities in Hcy metabolism may be responsible for the discrepancies observed
      between WKY rats and SHR concerning blood pressure and 3) to investigate whether
      a methionine-enriched diet, differently modified plasma and liver antioxidant
      status in WKY rats an SHR. We conclude that the increase in blood pressure in WKY
      rats is related to high plasma cysteine levels and is not due to a decrease in NO
      bioavailability and that the decrease in blood pressure in SHR is associated with
      high plasma GSH levels after methionine supplementation. So GSH synthesis appears
      to be stimulated by liver oxidative stress and GSH is redistributed into blood in
      SHR. So the great GSH synthesis can be rationalized as an autocorrective response
      that leads to a decreased blood pressure in SHR.

PMID- 14972348
TI  - Plasma molybdenum reflects dietary molybdenum intake.
AB  - The relationship between plasma molybdenum (Mo) and dietary intake has not been
      investigated in humans. We developed an isotope dilution method to determine
      molybdenum in 0.5 mL blood plasma by ICP-MS and conducted a study to determine
      the effect of dietary intake on plasma molybdenum. Twelve young men consumed a
      very low Mo diet (22 microg/day) for 24 days while confined to the WHNRC
      metabolic research unit and plasma molybdenum was monitored. (97)Mo was infused
      in four of the subjects (Group 1) to follow its clearance from the blood. The
      other eight remained in unit for 120 days (an additional 96 days). Four consumed
      the 22 microg/day molybdenum diet for 102 days followed by 467 microg/day for 18
      days (Group 2). and four consumed five levels of dietary molybdenum for 24 days
      each (Group 3). (100)Mo was added to the diet one or more times at each dietary
      level. Total plasma molybdenum and (100)Mo were monitored throughout the study.
      Plasma molybdenum in the 12 subjects decreased from 8.2 +/- 0.5 to 6.1 +/- 0.5
      nmol/L after 13 days of low molybdenum intake and was 5.1 +/- 0.5 nmol/L after 24
      days. In Group 2, average plasma molybdenum was 7.8 +/- 0.9 nmol/L at the
      beginning of the study, 5.4 +/- 0.4 nmol/L during the 102 days low molybdenum
      period, and 16.5 +/- 0.6 nmol/L during the high molybdenum period. Plasma
      molybdenum in Group 3 was 4.2 +/- 2.1 nmol/L at 22 microg/day; 5.8 +/- 2.5 nmol/L
      at 72 microg/day; 6.6 +/- 2.3 nmol/L at 121 microg/day; 19.7 nmol/L +/-2.1 at 467
      microg/day; and 43.9 +/- 2.1 nmol/L at 1490 microg/day. The results demonstrate
      that, in contrast to most other essential minerals, plasma molybdenum reflects
      low and high dietary molybdenum intakes within 14 days and may a useful indicator
      of low and high dietary intakes.

PMID- 14972349
TI  - Differences in the metabolic response to exogenous homocysteine in juvenile and
      adult rabbits.
AB  - Homocysteine has recently received a lot of attention as an independent risk
      factor for atherosclerotic and thrombotic cardiovascular disease. Plasma
      homocysteine levels tend to rise with age, but are also greatly influenced by
      nutritional factors. Early reports suggested that there were differences in the
      metabolism of homocysteine in adult and immature animals. The current work tests
      the hypothesis that adult and juvenile animals respond differently to chronic
      administration of homocysteine. We have previously found that adult rabbits given
      homocysteine parenterally twice daily for seven weeks developed progressive
      folate deficiency and concurrently developed an impairment of homocysteine
      metabolism. We now report that juvenile rabbits do not develop folate deficiency
      with chronic homocysteine loading and do not have progressively higher trough
      levels of homocysteine, as do the adults. In addition, juvenile rabbits that have
      been chronically pre-treated with homocysteine exhibit a lower peak homocysteine
      level after a single dose than do juvenile rabbits that have never received
      homocysteine. This adaptation did not occur in the adult rabbits. In addition,
      adult homocysteine-treated rabbits had evidence of oxidative stress as evidenced
      by higher levels of malondialdehyde in liver tissue than adult controls. The
      homocysteine-treated juvenile rabbits had the same levels of malondialdehyde as
      the juvenile control rabbits. We conclude that the plasma elimination kinetics
      are altered in juvenile rabbits in response to homocysteine pre-treatment. The
      difference in metabolism of homocysteine may protect the juvenile rabbits from
      the damaging effects of homocysteine. Future studies are planned to elucidate the
      mechanism of this adaptive response.

PMID- 14972350
TI  - Dietary oxidized cholesterol decreases expression of hepatic microsomal
      triglyceride transfer protein in rats.
AB  - The aim of this study was to compare the effects of dietary oxidized cholesterol
      and pure cholesterol on plasma and very low density lipoprotein (VLDL) lipids and
      on some parameters of VLDL assembly and secretion in rats fed two different
      dietary fats. Four groups of male growing Sprague-Dawley rats were fed diets
      containing pure or oxidized cholesterol (5 g/kg diet) with either coconut oil or
      salmon oil as dietary fat (100 g/kg diet) for 35 days. Rats fed oxidized
      cholesterol supplemented diets had significantly lower concentrations of
      triglycerides and cholesterol in plasma and VLDL than rats fed pure cholesterol
      supplemented diets irrespective of the type of fat. In addition, rats fed
      oxidized cholesterol supplemented diets had significantly lower relative
      concentrations of microsomal triglyceride transfer protein messenger ribonucleic
      acid (mRNA) than rats fed pure cholesterol supplemented diets. In contrast,
      hepatic lipid concentrations and the relative concentration of apolipoprotein B
      mRNA were not influenced by the dietary factors investigated. Parameters of
      hepatic lipogenesis (relative mRNA concentration of sterol regulatory element
      binding protein-1c and activity of glucose-6-phosphat dehydrogenase) were
      significantly reduced by feeding fish oil compared to coconut oil, but were not
      affected by the type of cholesterol. In conclusion, the data of this study
      suggest, that dietary oxidized cholesterol affects VLDL assembly and/or secretion
      by reducing the synthesis of MTP but not by impairing hepatic lipogenesis or
      synthesis of apolipoprotein B.

PMID- 14972351
TI  - Regulation of cysteine dioxygenase and gamma-glutamylcysteine synthetase is
      associated with hepatic cysteine level.
AB  - Two hepatic enzymes, cysteine dioxygenase (CDO) and gamma-glutamylcysteine
      synthetase (GCS), play important regulatory roles in the response of cysteine
      metabolism to changes in dietary sulfur amino acid or protein levels. To examine
      the time-course of changes in CDO and GCS activities, CDO and GCS-catalytic or
      heavy subunit protein and mRNA levels, and cysteine and glutathione levels, we
      adapted rats to either a low protein (LP) or high protein (HP) diet, switched
      them to the opposite diet, and followed these parameters over 6 days. Hepatic CDO
      activity and amount, but not mRNA level, increased in response to higher protein
      intake; the t(1/2) of change for CDO activity or protein level was 22 h for rats
      switched from a LP to a HP diet and 8 h for rats switched from a HP to a LP diet,
      suggesting that the HP diet decreased turnover of CDO. Hepatic GCS activity,
      catalytic subunit amount and mRNA level decreased in response to a higher protein
      intake. GCS catalytic subunit level changed with a similar t(1/2) for both
      groups, but the change in GCS activity in rats switched from a LP diet to a HP
      diet was faster (approximately 16h) than for rats switched from a HP to a LP diet
      (approximately 74h). Hepatic cysteine and glutathione levels reached new steady
      states within 12 h (LP to HP) or 24 h (HP to LP). CDO activity appeared to be
      regulated at the level of protein, probably by diminished turnover of CDO in
      response to higher protein intake or cysteine level, whereas GCS activity
      appeared to be regulated both at the level of mRNA and activity state in response
      to the change in cysteine or protein availability. These findings support a role
      of cysteine concentration as a mediator of its own metabolism, favoring
      catabolism when cysteine is high and glutathione synthesis when cysteine is low.

PMID- 14972352
TI  - Puberty onset in the female offspring of rats submitted to protein or energy
      restricted diet during lactation.
AB  - This study aims to determine the effects of maternal protein and energy
      malnutrition during lactation on the linear growth, body weight and onset of
      puberty of the female offspring. At parturition, dams were randomly assigned to
      the following groups: (C) control group, with free access to a standard
      laboratory diet containing 23% protein; (PR) protein-restricted group, with free
      access to an isoenergy and protein-restricted diet containing 8% protein; and
      (ER) energy-restricted group, receiving standard laboratory diet in restricted
      quantities. After weaning, the female pups had free access to standard laboratory
      diet. From day 30 onwards, the pups were inspected daily for vaginal opening.
      Cyclic stages of the ovaries were studied by daily vaginal smears after vaginal
      opening until day 40 when all animals were sacrificed with pentobarbital. From
      day 4 after birth until day 40, body weight and linear growth in the PR and ER
      rats were significantly lower than in controls (p < 0.001). In spite of the
      significant (p<0.05) delayed in the vaginal opening in PR and ER rats, the first
      estrous cycle occurred at the same time of vaginal opening in all groups. The PR
      and ER rats exhibited a lower uterine (PR = 42%, ER = 40%, p < 0.001) and ovarian
      (PR = 26%, ER=19%, p < 0.05) absolute weight and uterus relative weight (PR =
      27%, ER = 22%, p < 0.05). Our data showed that maternal protein and energy
      malnutrition during lactation leads to growth retardation and delayed on the
      onset of puberty in female pups, with vaginal opening and estrous cycle occurring
      at the same time.

PMID- 14972353
TI  - Attention and arousal related modulation of spontaneous gamma-activity in the
      auditory cortex of the cat.
AB  - Sensory information processing in neocortex is associated with rhythmic
      synchronized gamma frequency firing of sensory cortical units and similar
      frequency oscillations of the field potentials. Different aspects of the gamma
      activity (20-80 Hz) have been suggested as correlates of attention, arousal and
      sensory binding. It is clear that attention has a modality selective influence,
      while arousal has a more general effect on the sensory systems. We used an
      experimental conditioning paradigm to separate these differential effects of
      attention and arousal on spontaneous neocortical gamma activity. We recorded
      field potentials with epidural electrodes placed above the auditory cortical
      areas of cats. The animals performed a simple instrumental alimentary
      conditioning task with different modality (visual and auditory) conditioned
      stimuli. When they attended to the auditory conditioned stimulus, both frequency
      and power increase of spontaneous gamma activity were detected. However when they
      attended visual, we found no power increase of gamma activity recorded above
      auditory areas, while the frequency increase was the same as in the "attend
      auditory" condition. We conclude that the power modulation of gamma activity is
      modality specific and thus can be attributed to selective attention, whereas the
      frequency modulation of gamma activity shows no modality specificity, it is
      influenced by the arousal level.

PMID- 14972354
TI  - Access to numerical information is dependent on the modality of stimulus
      presentation in mental addition: a combined ERP and behavioral study.
AB  - We investigated whether the mental representation of numbers is abstract amodal
      or modality-dependent. Subjects verified simple additions. In an event-related
      potential (ERP) experiment, subjects added an Arabic digit (S2) to a preceding
      number (S1) offsetting 3 s before S2. S1 was either a visually shown Arabic
      digit, a written number word or an acoustically presented number word. In a
      behavioral experiment, we measured the speed of addition using a modified
      paradigm. In the ERPs to S2, the amplitude of the parietal N1, the fronto-central
      P2, and the late positivity between 320 and 460 ms were more positive and RTs
      were faster when S1 was a heard number word than when S1 was a written number
      word. ERP amplitudes and reaction times took intermediate positions between the
      other two conditions when S1 was an Arabic digit. Between the Arabic and heard
      number conditions, this so-called numeral modality effect (NME) was present at
      electrodes Pz, P4, P3 and Cz when number size was small, whereas it was
      significant over electrode C4 and P4 when number size was large. Our results
      suggest that numbers presented in different surface-formats have differential
      access to number representations. Conclusions for models of number processing are
      drawn and the possible role of parietal number representations is discussed. We
      replicated the N270 ERP component and elicited the ERP numerical distance effect
      in response to incongruent arithmetical results.

PMID- 14972355
TI  - Blind individuals show enhanced perceptual and attentional sensitivity for
      identification of speech sounds.
AB  - We report on enhanced processing of speech sounds in congenitally and early blind
      individuals compared with normally seeing individuals. Two different consonant
      vowel (CV) syllables were presented via headphones on each presentation. We used
      a dichotic listening (DL) procedure with pairwise presentations of CV syllables.
      The typical finding in this paradigm is a right ear advantage, indicating better
      processing of the CV-syllable stimuli in the left hemisphere. The dichotic
      listening procedure involved three different conditions, with instructions to pay
      attention to the right ear stimulus, the left ear stimulus or no specific
      instruction. The participants were 14 congenitally or early blind Finnish
      speaking individuals that were compared with 129 normal seeing Finnish-speaking
      individuals. The blind participants reported overall significantly more correct
      syllables than seeing control subjects. When instructed to pay attention to the
      left ear stimulus and only report from the attended channel, they were again
      significantly better than the seeing control subjects. These findings indicate
      effects of hemispheric reorganization in blind individuals at both the sensory
      and cognitive levels of information processing in the auditory sensory modality.

PMID- 14972356
TI  - Differential modulation of temporal and frontal components of the somatosensory
      N140 and the effect of interstimulus interval in a selective attention task.
AB  - The modulation of the somatosensory N140 was examined in a selective attention
      task where a control condition was applied and the interstimulus interval (ISI)
      was varied. Electrical stimuli were randomly presented to the left index (p=0.4)
      and middle fingers (p=0.1), and right index (p=0.4) and middle fingers (p=0.1).
      In the attend-right condition, subjects were instructed to count silently the
      number of infrequent target stimuli presented to the right middle finger, and to
      the left middle finger in the attend-left condition. They had no task in the
      control condition. Each condition was performed with two different sets of ISI
      (mean 400 vs. 800 ms). The somatosensory N140 elicited by frequent standard
      stimuli was analyzed. The N140 amplitude was larger for the attended ERP compared
      to the control and unattended ERPs. This attention effect was more marked at the
      frontal electrodes compared to the temporal electrodes contralateral to the
      stimulation side. Furthermore, the attention effect at the frontal electrode was
      larger when the ISI was 800 ms than when it was 400 ms. The N140 amplitude did
      not differ between the control and unattended ERPs, which might show that a small
      processing negativity (PN) occurred during the control condition or difference in
      vigilance level between them. In conclusion, the early lateral ("temporal") and
      late midline ("frontal") components of the N1 (N140) show different behavior, and
      thus may have different functional significance. Enhancement of the attention
      effect at the frontal electrode in the longer ISI condition supports the
      hypothesis that it is related to stronger, voluntary maintenance of the
      attentional trace.

PMID- 14972357
TI  - Response selection and execution in patients with Parkinson's disease.
AB  - Different studies report diverse, sometimes conflicting findings, regarding the
      ability of Parkinson's disease (PD) patients to benefit from advanced cuing in
      choice reaction time (RT). Thus, conclusions about the changed state of
      underlying processes such as set formation, motor programming and motor
      initiation are not certain. In the present study, visual choice RT testing that
      utilized brief (100 ms) color signals (red/blue), was followed by auditory choice
      reaction time (CRT) testing with brief (100 ms) low/high pitch sound stimuli.
      Response consisted of either index or middle finger flexion. The signals were
      then combined so that the color stimuli cued the sound stimuli with an 800-ms
      interstimuli interval. Cuing validity was reduced from 100% during training to
      76% during final testing. In addition, the same sound stimuli were presented
      randomly, without visual cuing, in which case response should have been
      suppressed. Tested subjects include 19 moderate PD patients, 21 elderly controls
      and 20 young controls. The patients did not differ from the controls in error
      rate but were slower to respond, except under 100% congruent cuing, indicating
      that their extended RT in CRT results from slowed stimulus-response linking and
      not from impaired motor initiation/execution. In the final condition patients
      showed no perseverance and demonstrated normal speed of set shifting in
      incongruent trials.

PMID- 14972358
TI  - Supplementary motor area provides an efferent signal for sensory suppression.
AB  - Voluntary actions produce suppression of neural activity in sensory areas, and
      reduced levels of conscious sensation. Recent computational models of motor
      control have linked sensory suppression to motor prediction: an efferent signal
      from motor areas may cancel the sensory reafferences predicted as a consequence
      of movement. Direct evidence for the efferent mechanism in sensory suppression
      has been lacking. We investigated the perceived size of finger-muscle twitches
      (MEPs) evoked by TMS in eight normal subjects. Subjects freely chose on each
      trial whether to make or withhold a voluntary flexion of the right index finger,
      in synchrony with an instructional stimulus. A test MEP occurred at the
      instructed time of action. The subject then relaxed and a second reference MEP
      occurred a few seconds later. Subjects judged which of the two MEPs was larger.
      Subjects perceived the first test MEP to be smaller in trials where they made
      voluntary actions than on trials where they did not, demonstrating sensory
      suppression. On randomly selected trials, a conditioning prepulse was delivered
      over the supplementary motor area (SMA) 10 ms before the pulse producing the test
      MEP. The SMA prepulse reduced and almost abolished the sensory suppression effect
      in voluntary action trials. We suggest the SMA may provide an efferent signal
      which is used by other brain areas to modulate somatosensory activity during self
      generated movement.

PMID- 14972359
TI  - Seeing words in context: the interaction of lexical and sentence level
      information during reading.
AB  - The ERP experiment reported here addresses some outstanding questions regarding
      word processing in sentential contexts: (1) Does only the 'message-level'
      representation (the representation of sentence meaning combining lexico-semantic
      and syntactic constraints) affect the processing of the incoming word [J. Exp.
      Psychol.: Learn. Mem. Cogn. 20 (1994) 92]? (2) Is lexically specified semantic
      relatedness between multiple words the primary factor instead [J. Exp. Psychol.:
      Learn. Mem. Cogn. 15 (1989) 791]? (3) Alternatively, do word and sentence level
      information interact during sentence comprehension? Volunteers read sentences
      (e.g. Dutch sentences resembling The javelin was by the athletes...) in which the
      (passive) syntactic structure and the semantic content of the lexical items
      together created a strong expectation of a specific final word (e.g., thrown),
      but also sentences in which the syntactic structure was changed from passive to
      active (e.g. Dutch sentences resembling The javelin has the athletes...), which
      altered the message level constraint substantially and strongly reduced the
      expectation of any particular completion. Half of the sentences ended in a final
      word with a good lexico-semantic fit relative to the preceding content words
      (e.g. thrown, fitting well with the preceding javelin and athletes). This creates
      very plausible sentences in the strong constraint context but semantically
      anomalous ones in the weakly constraining context (e.g., The javelin has the
      athletes thrown). In the other half the final word had a poor lexico-semantic fit
      (e.g., summarized that does not fit at all with javelin and athletes). Good
      lexico-semantic fit endings showed no difference in N400 amplitude in the strong
      and weak message-level constraint sentences, despite the fact that the latter
      were semantically anomalous. This result suggests that lexico-semantic fit can be
      more important for word processing than the meaning of the sentence as determined
      by the syntactic structure, at least initially. These conditions did differ,
      however, in the region of the P600 where the anomalous weak constraint version
      was much more positive, a pattern usually seen with ungrammatical sentences. The
      processing of poor lexico-semantic fit words showed a quite different pattern; in
      both strong and weak constraint sentences they elicited a substantial N400
      effect, but N400-amplitude was significantly more negative following strong
      constraint contexts, even though both sentence contexts were equivalently
      anomalous. Taken together, these findings provide evidence for the importance of
      both message-level and lexico-semantic information during sentence comprehension.
      The implications for theories of sentence interpretation are discussed and an
      extension of the message-based hypothesis will be proposed.

PMID- 14972360
TI  - Reinforcement-related neurons in the primate basal forebrain respond to the
      learned significance of task events rather than to the hedonic attributes of
      reward.
AB  - The objective of this study was to determine if the responses of basal forebrain
      neurons are related to the cognitive processes necessary for the performance of
      behavioural tasks, or to the hedonic attributes of the reinforcers delivered to
      the monkey as a consequence of task performance. In all cases, it was found that
      the primary neuronal responses were to visual stimuli that required analysis
      important for the selection of a behavioural response and not to the delivery of
      reinforcement per se. Indeed, reinforcement-related neurons that responded only
      to the delivery of juice or of saline were never encountered. In additional
      experiments, it was found that abstract visual cues-specific gestures of the
      experimenter-that signaled the impending delivery of reinforcement were able to
      activate these neurons. These data are consistent with the view that
      reinforcement-related basal forebrain neurons influence the sensory and motor
      processes in the cerebral cortex, providing control signals that optimise the
      processing of complex sensory stimuli and/or the generation of appropriate
      behavioural responses.

PMID- 14972361
TI  - Intra-subject replication of brain magnetic activity during the processing of
      speech sounds.
AB  - The present study examined the cortical activity during processing of vocalic
      segments by means of whole-head magnetoencephalography (MEG) to see whether
      respective cortical maps are stable across repeated measurements. We investigated
      the spatial configuration and temporal characteristics of the N100m generators of
      the auditory-evoked field during the processing of the synthetic German vowels
      [a], [e] and [i] across 10 repeated measurements in a single subject. Between
      vowels, N100m latency as well as source location differences were found with the
      latency differences being in accordance with tonochronic principles. The spatial
      configuration of the different vowel sources was related to differences in
      acoustic/phonological features. Vowels differing maximally in those features,
      i.e., [a] and [i], showed larger Euclidean distances between N100m vowel sources
      than [e] and [i]. This pattern was repeatable across sessions and independent of
      the source modeling strategy for left-hemispheric data. Compared to a pure tone
      control condition, the N100m generators of vowels were localized in more
      anterior, superior and lateral parts of the temporal lobe and showed longer
      latencies. Being aware of the limited significance of conclusions drawn from a
      single case study, the study yielded a repeatable spatial and temporal pattern of
      vowel source activity in the auditory cortex which was determined by the
      distinctiveness of the formant frequencies corresponding to abstract phonological
      features.

PMID- 14972362
TI  - Gender-specific hemispheric asymmetry in auditory space perception.
AB  - This study aimed to investigate gender-related functional asymmetries in monaural
      sound localization in the vertical plane. In a simple pointing task, right-handed
      subjects localized vertical positions of sound sources using only one ear.
      Results show that females were more precise when listening with the left ear,
      while males did better with the right. However, significant differences in
      monaural localization performance as a function of gender occurred exclusively
      when listening with the right ear, with males performing substantially more
      precisely than females. These findings suggest gender-related differences in the
      intrahemispheric functional organization of the left hemisphere for the
      processing of monaural spatial cues. It is proposed that the results may be
      related to the sexual dimorphism of the posterior parietal cortex, or planum
      temporale, both areas known to be involved in spatial auditory functions.

PMID- 14972363
TI  - Smooth pursuit under stimulus-response uncertainty.
AB  - Simple reaction times (RTs) are typically faster than choice reaction times and
      increase with uncertainty according to Hick's law. Here we show that smooth
      pursuit eye movement RTs show no effect of SR uncertainty while joystick tracking
      shows a step change between SRT and CRT, but no significant increases beyond two
      choices. The results suggest there is a benefit to pre-programming joystick
      tracking but not for smooth pursuit eye movements (SPEMs).

PMID- 14972364
TI  - Oral choline increases choline metabolites in human brain.
AB  - Choline, a precursor of acetylcholine and phosphatidylcholine, is largely
      obtained from the diet. Animal studies demonstrate increased choline metabolites
      in brain following oral administration. Several proton magnetic resonance
      spectroscopy ((1)H-MRS) reports differ as to whether similar increases are
      observable in human subjects. This study was designed to minimize intra-subject
      variance and thereby maximize the ability to determine if a significant increase
      in brain choline can be detected after choline ingestion. (1)H-MRS was performed
      continuously for 2.5 h on 11 healthy young males following choline ingestion.
      Nine of the original subjects returned for identical scans without choline
      ingestion. Following oral choline, there was a statistically significant increase
      in the choline signal (Cho) measured from the left putamen, representing choline
      containing compounds, as measured against creatine (Cr) or N-acetylaspartate
      (NAA). The mean increase in Curve maxima (C(max)) is 6.2% for Cho/Cr and 3.0% for
      Cho/NAA. The Mean Time to C(max) (T(max)) was approximately 2 h after ingestion.
      A 3-6% increase in Cho by MRS likely corresponds to a 10-22% increase in
      phosphocholine, similar to findings in animal studies. In conclusion, a
      significant increase in choline-containing compounds in human brain can be
      detected by (1)H-MRS after choline ingestion in young subjects.

PMID- 14972365
TI  - A select group of perpetrators of domestic violence: evidence of decreased
      metabolism in the right hypothalamus and reduced relationships between
      cortical/subcortical brain structures in position emission tomography.
AB  - In an earlier study, we reported that some perpetrators of domestic violence
      evidenced exaggerated fear-related responses to the panicogenic agent sodium
      lactate. In the current study, we employed positron emission tomography (PET) to
      investigate our hypothesis that there are differences in the neural structures
      and/or pathways that mediate and control the expression of fear-induced
      aggression in perpetrators of domestic violence. Regional cerebral glucose
      metabolism was measured in eight male perpetrators of domestic violence who
      fulfilled DSM-III-R criteria for alcohol dependence (DV-ALC), 11 male
      participants who fulfilled DSM-III-R criteria for alcohol dependence and had no
      history of interpersonal aggression (ALC) and 10 healthy male participants who
      did not fulfill criteria for any DSM-III-R axis I diagnosis and had no history of
      interpersonal aggression (HCS). DV-ALC had a significantly lower mean glucose
      uptake in the right hypothalamus compared to ALC and HCS. Correlations were
      performed between measures of glucose utilization in the brain structures
      involved in fear-induced aggression. The comparison of DV-ALC to HCS and to ALC
      differed in six and seven comparisons, respectively, involving various cortical
      and subcortical structures. HCS and ALC differed between the left thalamus and
      the left posterior orbitofrontal cortex. These PET findings show that some
      perpetrators of domestic violence differ from control participants in showing
      lower metabolism in the right hypothalamus and decreased correlations between
      cortical and subcortical brain structures. A possible psychological covariate of
      these changes in regional activity might be fear-induced aggression, but this
      hypothesis should be examined in larger study groups that undergo provocation
      during imaging.

PMID- 14972366
TI  - Temporal lobe abnormalities in semantic processing by criminal psychopaths as
      revealed by functional magnetic resonance imaging.
AB  - We tested the hypothesis that psychopathy is associated with abnormalities in
      semantic processing of linguistic information. Functional magnetic resonance
      imaging (fMRI) was used to elucidate and characterize the neural architecture
      underlying lexico-semantic processes in criminal psychopathic individuals and in
      a group of matched control participants. Participants performed a lexical
      decision task in which blocks of linguistic stimuli alternated with a resting
      baseline condition. In each lexical decision block, the stimuli were either
      concrete words and pseudowords or abstract words and pseudowords. Consistent with
      our hypothesis, psychopathic individuals, relative to controls, showed poorer
      behavioral performance for processing abstract words. Analysis of the fMRI data
      for both groups indicated that processing of word stimuli, compared with the
      resting baseline condition, was associated with neural activation in bilateral
      fusiform gyrus, anterior cingulate, left middle temporal gyrus, right posterior
      superior temporal gyrus, and left and right inferior frontal gyrus. Analyses
      confirmed our prediction that psychopathic individuals would fail to show the
      appropriate neural differentiation between abstract and concrete stimuli in the
      right anterior temporal gyrus and surrounding cortex. The results are consistent
      with other studies of semantic processing in psychopathy and support the theory
      that psychopathy is associated with right hemisphere abnormalities for processing
      conceptually abstract material.

PMID- 14972367
TI  - Thought disorder and nucleus accumbens in childhood: a structural MRI study.
AB  - Thought disorder has been described as a hallmark feature in both adult and
      childhood-onset schizophrenia. The nucleus accumbens (NAc) has been repeatedly
      proposed as a critical station for modulating gating of information flow and
      processing of information within the thalamocortical circuitry. The aim of the
      present study was to investigate the relationship of thought disorder measures,
      which were administered to 12 children with schizophrenia and 15 healthy age
      matched controls, and NAc volumes obtained from high-resolution volumetric
      magnetic resonance imaging analyses. The propensity for specific thought disorder
      features was significantly related to NAc volumes, despite no statistically
      significant differences in the NAc volumes of children with schizophrenia and
      normal children. Smaller left NAc volumes were significantly related to poor on
      line revision of linguistic errors in word choice, syntax and reference. On the
      other hand, underuse of on-line repair of errors in planning and organizing
      thinking was significantly associated with decreased right NAc volumes. The
      results of this pilot study suggest that the NAc is implicated in specific
      thought patterns of childhood. They also suggest that subcortical function in the
      NAc might reflect hemispheric specialization patterns with left lateralization
      for revision of linguistic errors and right lateralization for repair strategies
      involved in the organization of thinking.

PMID- 14972368
TI  - Cerebral ventricular change over the first 10 years after the onset of
      schizophrenia.
AB  - Whether the brain structural abnormalities seen in schizophrenia are progressive
      is controversial. We previously reported on a longitudinal study of 50 first
      episode patients with schizophrenia and 20 controls who had serial MRI scans
      during the first 5 years of illness. Greater enlargement of lateral ventricles
      and reduction of hemispheric volume was observed over time in the patients
      compared with controls. The present study obtained MRI scans from 26 of these
      patients and 10 controls at a follow-up 10 years subsequent to their first
      evaluations. The initial, 4-5th and 10th year scans were examined for the degree
      of change in ventricular and hemispheric volume. Significantly greater
      ventricular enlargement during the second 5 years was detected in the patient
      cohort compared with controls (P<0.05) with nine of the patients having
      ventricular enlargement (as measured by percent change) occurring at a rate
      exceeding that of any of the controls from years 1 through 10. The rate of
      ventricular change during the first 5 years was significantly correlated with age
      at first hospitalization, and ventricular enlargement in years 5-10 was
      correlated with the amount of time spent in hospital. Paradoxically, greater
      change in ventricles over time was correlated with better, not worse, outcome at
      the 10th year of follow-up with regard to the presence of symptoms. These data
      suggest heterogeneity in the course of brain change whereby some patients may
      exhibit active structural brain change only early in their illness or not at all
      after their first episode, while others continue to exhibit ventricular change
      spanning the decade subsequent to their first episode. Despite these differences
      among patients, the present study fails to detect any relationship of ventricular
      enlargement to poorer outcome as has been reported by other investigators.

PMID- 14972369
TI  - State-related changes in cerebral white matter may underlie psychosis
      exacerbation.
AB  - Previous reports have described accelerated loss of cerebral white matter in
      schizophrenia. Others have reported changes of ventricle volumes in schizophrenic
      patients, with greatest increases following remission of psychotic symptoms. In
      this study changes in cerebral white matter volumes and psychotic symptoms were
      measured in 16 recently decompensated schizophrenic patients from neuroleptic
      free baseline to 4 weeks later during treatment with antipsychotics. Serial white
      matter assessments were also performed in eight controls at similar intervals.
      Thirteen of 16 patients showed reduction of psychotic symptoms (reduction of SAPS
      scores by 24.4+/-12.6) during treatment. Three patients failed to respond
      (increase of SAPS scores by 15.7+/-13.8). Serial volumetric studies of cerebral
      white matter during the 4-week period showed a decrease of white matter volume in
      the responders by 8.2+/-8.2 cm(3) (P=0.003). Patients who failed to respond
      showed a non-significant increase in white matter during the same period by
      11.4+/-11.7 cm(3). Absolute and percentage changes change in white matter volumes
      during the 4-week period were positively correlated with changes in SAPS scores
      (both P<0.01). Cerebral white matter, composed of myelin-containing
      oligodendrocytes, is highly sensitive to excitotoxicity. Swelling of myelin and
      of white matter, associated interference with the speed of neurotransmission
      through myelinated axons, and dyssynchrony of information processing by
      subcortical and cortical networks may be associated with psychosis exacerbation.
      Partial remission of symptoms may mark temporary reduction of an active, toxic
      process that interferes with information processing.

PMID- 14972370
TI  - Lack of sex differences in striatal dopamine D2 receptor binding in drug-naive
      schizophrenic patients: an IBZM-SPECT study.
AB  - Differences in antipsychotic treatment response, clinical course and outcome of
      schizophrenia could be related to gender-related cerebral differences in anatomy
      and function. The aim of the study was to assess sex differences in the striatal
      dopamine D2 receptor binding in 15 drug-naive schizophrenic patients (seven
      males, eight females) using (123)I-IBZM single photon emission computed
      tomography. Basal ganglia/frontal cortex (BG/FC) uptake ratios were obtained. No
      significant differences were found in global, left and right BG/FC ratios or
      laterality indices between males and females. No correlation was found between
      BG/FC ratios and age, duration of illness or scores on symptom rating scales. Our
      data indicate a lack of sex differences in striatal D2 receptor binding in drug
      naive schizophrenic patients and do not support previous reports of left
      lateralized striatal asymmetry in male schizophrenic patients.

PMID- 14972371
TI  - Dopamine transporter density of the basal ganglia assessed with [123I]IPT SPECT
      in drug-naive children with Tourette's disorder.
AB  - There is evidence that abnormalities in the dopaminergic system involving the
      dopamine transporter (DAT) are involved in the pathophysiology of Tourette's
      disorder (TD) from previous studies using [(123)I]2beta-carbomethoxy-3-(4
      iodophenyl)tropane ([(123)I]beta-CIT) and single photon emission tomography
      (SPECT). However, because those studies were performed in medicated adult
      patients with TD, we decided to compare DAT densities in nine drug-naive children
      with TD and eight normal children. The children with TD did not suffer from
      associated psychiatric problems such as obsessive-compulsive symptoms, attention
      deficit hyperactivity disorder, anxiety, depression and developmental
      difficulties. We performed brain SPECT 2 h after the intravenous administration
      of I-123N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl)tropane
      ([(123)I]IPT) and carried out both quantitative and qualitative analyses using
      the obtained SPECT data, which were reconstructed for the assessment of the
      specific/non-specific DAT binding ratio in the basal ganglia. We then
      investigated the correlation between the severity of tics in children with TD
      assessed with the Yale Global Tic Severity Scale (YGTSS) and the specific/non
      specific DAT binding ratio of the basal ganglia. Drug-naive children with TD
      showed a significantly increased specific/non-specific DAT binding ratio in the
      basal ganglia compared with normal children that did not correlate significantly
      with the severity of tics. Our results with drug-naive children with TD between
      the ages of 6 and 12 may help to clarify previous findings concerning DAT binding
      in adult patients with TD and suggest that DAT densities may be associated
      directly with the pathophysiology of TD, regardless of disease progress or drug
      effect.

PMID- 14972372
TI  - Right hemispheric dysfunction in a case of pure progressive aphemia: fusion of
      multimodal neuroimaging.
AB  - This article describes the unusual case of a 60-year-old woman suffering from
      pure progressive aphemia. The fusion of multimodal neuroimaging (MRI, perfusion
      SPECT) implicated the right frontal lobe, especially the inferior frontal gyrus.
      This area also showed the greatest functional MRI activation during the
      performance of a covert phonemic fluency task. Results are discussed in terms of
      bihemispheric language representation. The fusion of three sets of neuroimages
      has aided in the interpretation of the patient's cognitive brain dysfunction.

PMID- 14972373
TI  - A case of Cotard syndrome: (123)I-IBZM SPECT imaging of striatal D(2) receptor
      binding.
AB  - A case of 'delire de negation' that suddenly appeared in a 43-year-old male is
      presented. No alteration in regional cerebral blood, as measured by (99m)Tc-HMPAO
      SPECT, was found, but (123)I-IBZM-SPECT analysis showed reduced striatal D(2)
      receptor binding that further decreased after treatment.

PMID- 14972374
TI  - Reliability of interpretation of gram-stained vaginal smears by Nugent's scoring
      system for diagnosis of bacterial vaginosis.
AB  - This study was designed to assess reliability of interpretation of Gram-stained
      vaginal smears by using Nugent's scoring system for diagnosis of bacterial
      vaginosis (BV) across three different centers in Turkey: two in Ankara and one in
      Trabzon. The vaginal smears were collected from clients attending a family
      planning clinic in Trabzon, Turkey during October-December 1997. One slide taken
      from each client was prepared according to the standard methods and enumerated.
      One evaluator from each center examined the slides independently for the presence
      of BV and none of them had access to the evaluation of the others. Out of 372
      slides, 301 (81%) were found to be satisfactory for scoring by all three
      evaluators and included in the analysis. Nugent's scores from 1-10 reported from
      each evaluator were compared by Spearman correlation coefficients and Kappa
      statistics. The difference in the proportions of BV diagnosis in three centers
      was evaluated by chi2 test. There was good agreement for the interpretation of
      Gram-stained vaginal smears by Nugent's scoring system for diagnosis of BV. These
      results indicate that it is a reliable method in diagnosis of BV at different
      settings.

PMID- 14972375
TI  - "Streptococcus milleri" endocarditis caused by Streptococcus anginosus.
AB  - Unlike other viridans streptococci, members of the "Streptococcus milleri group"
      are often associated with abscess formation, but are only rare causes of
      infective endocarditis. Although it has been shown that almost all S. intermedius
      isolates and most S. constellatus isolates, but only 19% of S. anginosus
      isolates, were associated with abscess formation, no report has addressed the
      relative importance of the 3 species of the "S. milleri group" in infective
      endocarditis. During a 5-year period (April 1997 through March 2002), 6 cases of
      "S. milleri" endocarditis (out of 377 cases of infective endocarditis), that
      fulfil the Duke's criteria for the diagnosis of infective endocarditis, were
      encountered. All 6 "S. milleri" isolates were identified as S. anginosus by 16S
      ribosomal RNA (rRNA) gene sequencing. Three patients had underlying chronic
      rheumatic heart disease and 1 was an IV drug abuser. Five had monomicrobial
      bacteremia, and 1 had polymicrobial (S. anginosus, S. mitis, Granulicatella
      adiacens, and Slackia exigua) bacteremia. Two patients died. None of the 6
      isolates were identified by the Vitek system (GPI) or the API system (20 STREP)
      at >95% confidence. All 6 isolates were sensitive to penicillin G (MIC 0.008
      0.064 microg/mL), cefalothin, erythromycin, clindamycin, and vancomycin. Accurate
      identification to the species level, by 16S rRNA gene sequencing, in cases of
      bacteremia caused by members of the "S. milleri group", would have direct
      implication on the underlying disease process, hence guiding diagnosis and
      treatment. Infective endocarditis should be actively looked for in cases of
      monomicrobial S. anginosus bacteremia, especially if the organism is recovered in
      multiple blood cultures.

PMID- 14972376
TI  - The effect of systemic antibiotics on the microbiological diagnosis of
      experimental foreign body infections caused by Staphylococcus epidermidis.
AB  - Qualitative broth culture and quantitative culture on agar were compared with
      quantitative polymerase chain reaction (PCR) for the diagnosis of foreign body
      infections (FBI) in a rat model with and without exposure to systemic antibiotics
      (teicoplanin and rifampin). The 3 methods had a similar and high yield without
      antibiotics. Antibiotics decreased the number of CFU/foreign body and increased
      the number of culture-negative foreign bodies and the variability of the results
      in quantitative culture. The yield of broth culture remained high under
      antibiotics although prolonged incubation (2-5 days) was required. The yield of
      the PCR was equivalent or even superior (for teicoplanin) to the yield of broth
      culture. Quantitative PCR had a higher yield and lower variability than
      quantitative culture and was not affected by antibiotics. The simultaneous
      isolation of RNA from all samples indicated viability of the bacteria.
      Quantitative PCR seems a promising method for the diagnosis of FBI.

PMID- 14972377
TI  - The occurrence of Chlamydia pneumoniae, Mycoplasma pneumoniae, and herpesviruses
      in otitis media with effusion.
AB  - In a previous report we found Chlamydia (C.) pneumoniae to be present in middle
      ear fluids (MEE) from older children with otitis media with effusion (OME).
      However, OME is a disease of younger children the present study was conducted in
      toddlers. MEEs (n = 150) and nasopharynx samples (n = 83) from children with OME
      was analyzed by PCR for the presence of C. pneumoniae and Mycoplasma (M.)
      pneumoniae. C. pneumoniae was not present in any and M. pneumoniae only in one of
      the MEEs, and these pathogens could be demonstrated in one and two nasopharynx
      samples, respectively. Further, 133 MEEs were analyzed by PCR for the presence of
      the 8 human herpesviruses, and all samples were found to be negative. We conclude
      that neither C. pneumoniae or M. pneumoniae, or any of the 8 human herpesviruses
      seems to play a major role in the pathogenesis of OME in early childhood OME.

PMID- 14972378
TI  - In vitro susceptibilities of rare Candida bloodstream isolates to ravuconazole
      and three comparative antifungal agents.
AB  - We determined the in vitro susceptibilities of 643 strains of Candida spp.,
      representing 13 species rarely isolated from blood, to ravuconazole as well as
      three licensed systemic antifungal agents (amphotericin B, fluconazole, and
      flucytosine). The organisms included 234 isolates of C. krusei, 102 isolates of
      C. guilliermondii, 103 isolates of C. lusitaniae, 18 isolates of C. famata, 29
      isolates of C. kefyr, 20 isolates of C. pelliculosa, 13 isolates of C. rugosa,
      101 isolates of C. dubliniensis, 4 isolates of C. inconspicua, 11 isolates of C.
      lipolytica, 1 isolate of C. sake, and 2 isolates of C. lambica and 5 isolates of
      C. zeylanoides. MIC determinations were made by the National Committee for
      Clinical Laboratory Standards reference broth microdilution method and Etest
      (amphotericin B). Ravuconazole demonstrated excellent activity (98% susceptible
      at MIC < or = 1 microg/mL) against all species with the exception of C.
      inconspicua (75% [3 of 4]). By comparison, decreased susceptibility to
      fluconazole and/or amphotericin B was observed among isolates of C. krusei, C.
      guilliermondii, C. famata, C. rugosa, C. inconspicua, and C. lambica. These
      findings illustrate the fact that many of the less common species of Candida
      exhibit decreased susceptibility to one or more of the established systemically
      active antifungal agents. Ravuconazole is clearly an "extended-spectrum" triazole
      with potent in vitro activity against these rare and potentially "emerging"
      opportunistic pathogens.

PMID- 14972379
TI  - Two mycobacterium fortuitum strains isolated from pulmonary tuberculosis patients
      in Delhi harbour IS6110 homologue.
AB  - We report 2 isolates of Mycobacterium fortuitum from patients with pulmonary
      tuberculosis lesions hybridizing to IS6110 probe in restriction fragment length
      polymorphism (RFLP) typing. Results of polymerase chain reaction-hybridization
      formats using the non-specific region of IS6110 for the molecular detection of
      mycobacteria in clinical material should be interpreted with caution.

PMID- 14972380
TI  - Genetic and phenotypic characterization of pyrazinamide-resistant mycobacterium
      tuberculosis complex isolates in Japan.
AB  - The pncA gene mutations associated with pyrazinamide (PZA) resistance in
      Mycobacterium tuberculosis complex were determined in 26 PZA-resistant isolates
      in Japan. Of the 26 PZA-resistant isolates included, 21 were negative for
      pyrazinamidase (PZase). Of these, 20 isolates had various pncA mutations,
      resulting in alteration of primary amino acid sequence. However, 1 PZase-negative
      isolate did not have any mutation on pncA gene. The remaining 5 PZA-resistant
      isolates were positive for PZase and had identical pncA alleles with PZA
      susceptible isolates. IS6110 RFLP analysis demonstrated various distinct IS6110
      types and 5 pairs of isolates were very close to each other (>90% identical
      pattern). This study demonstrates that most of the PZA resistance is a result of
      various mutations on pncA resulting in loss of PZase activity. Further
      investigation, particularly on PZase-positive but PZA-resistant isolates and a
      PZase-negative isolate with no mutation on pncA, should be urgently done.

PMID- 14972381
TI  - Echinococcus granulosus in Jordan: assessment of various antigenic preparations
      for use in the serodiagnosis of surgically confirmed cases using enzyme immuno
      assays and the indirect haemagglutination test.
AB  - The Enzyme linked immunosorbent Assay (ELISA), indirect haemagglutination (IHA),
      and immunoblot techniques (IB) were used for the serodiagnosis of surgically
      confirmed cystic echinococcosis (CE) caused by the tapeworm Echinococcus
      granulosus. Antigens used for the detection of IgG or total antibodies included
      crude sheep hydatid fluid (CSHF), autoclaved antigen B (AAB), boiled antigen B
      (BAB), and homogenate protoscoleces antigen (HPA). The overall sensitivity of the
      ELISA and IHA tests used for the serodiagnosis of 57 surgically confirmed human
      cases was 91.2% and 68.4%, respectively. The sensitivity of both tests was
      comparable in groups whose sera were collected one week before surgery and up to
      one year after surgery at 95.8% and 87.5%, respectively. In contrast, the
      sensitivity of the ELISA was significantly higher than that of IHA for sera of
      patients collected after one year of surgery. There was a positive correlation (r
      = 0.61) between the titers of antibodies detected by the ELISA and IHA. Using the
      IB technique, antigen B fractions (8/12, 16, and 24 KDa) were detectable by sera
      of 68.4% using either CSHF or AAB, 49.1% using BAB and 22.8% using HPA as
      detecting antigens. The overall sensitivity of the three AgB fractions was
      identical or similar to that of the 8/12 KDa fraction alone, indicating that the
      detection of the latter fraction is sufficient for the serodiagnosis of CE
      infection in humans. In conclusion, the ELISA is the test of choice for the
      serodiagnosis of CE and the follow up of cases following surgery using CSHF as an
      antigen. The IB test is a confirmatory test when antigen B fractions of CSHF or
      AAB are detected.

PMID- 14972382
TI  - Pharmacokinetic/pharmacodynamic modeling can help guide targeted antimicrobial
      therapy for nosocomial gram-negative infections in critically ill patients.
AB  - Critically ill patients have altered pharmacokinetics (PK) that need to be
      considered when choosing and dosing antibiotics. We conducted a prospective,
      observational study to assess clinical and microbiologic response rates in 19
      critically ill patients with nosocomial Gram-negative infections. Antibiotics
      were dosed based on a mathematical pharmacodynamic (PD) model accounting for
      these altered kinetic parameters. The average APACHE II score +/- SE on intensive
      care unit admission and at the time of infection was 13.6 +/- 1.2 and 14.6 +/-
      1.1, respectively. With targeted antimicrobial therapy adjusted to achieve an
      optimal PD profile, 17/19 (89%) patients had a clinical cure or improvement and
      16/19 (84%) had either microbiologic eradication or presumed eradication.
      Modeling PD in these critically ill patients resulted in good clinical and
      microbiologic outcomes.

PMID- 14972383
TI  - Prevalence and characterization of metallo-beta-lactamases in clinical isolates
      of pseudomonas aeruginosa.
AB  - The prevalence and the type(s) of metallo-beta-lactamases (MBLs) produced by
      isolates of Pseudomonas aeruginosa were investigated. During 2001, 506
      nonduplicate isolates were obtained from hospitalized patients. Eighty-two
      strains were selected because of resistance to carbapenems and/or ceftazidime.
      Screening for MBL production was performed in the latter isolates by the Etest
      MBL strips (AB Biodisk, Solna, Sweden) and by a broth microdilution method
      measuring minimum inhibitory concentrations (MICs) of imipenem alone and in the
      presence of metal-chelating agents (EDTA and o-phenanthroline). Specific DNA
      probes were used to investigate the presence of genes coding for IMP- or VIM-type
      enzymes. Overall, four isolates of P. aeruginosa (obtained from independent
      patients) were found to carry a blaVIM gene. Polymerase chain reaction (PCR)
      experiments and DNA sequencing revealed that the VIM-2 determinant was present in
      three cases, whereas VIM-1 was detected in one isolate. Surveillance programs
      should be adopted to avoid the spread of these worrisome resistance genes.

PMID- 14972384
TI  - Worldwide assessment of dalbavancin activity and spectrum against over 6,000
      clinical isolates.
AB  - Continuing emergence of new antimicrobial resistance mechanisms and the increased
      frequency of existing resistances, requires the development of alternative
      antimicrobial agents. Dalbavancin is an amide glycopeptide derivative with a
      markedly extended serum elimination half-life. Dalbavancin and selected
      comparators were tested against 6,339 recent clinical isolates (2002) from the
      Americas and Europe using reference susceptibility testing methods. The general
      characteristics of this Gram-positive organism collection were: oxacillin (OXA)
      resistant Staphylococcus aureus (ORSA) at 39% of strains; vancomycin-resistant
      enterococci (VRE) at 10%; and penicillin-nonsusceptible pneumococci at 28%. The
      overall distribution of dalbavancin minimum inhibitory concentration (MIC) values
      ranged from < or = 0.015 to > 32 microg/ml, but > 99% of MIC results were at < or
      =1 microg/ml. S. aureus and coagulase-negative staphylococci were extremely
      susceptible to dalbavancin (MIC90, 0.06 microg/ml) despite resistance patterns to
      other agents. Dalbavancin was the most potent compound (by weight) against
      vancomycin-susceptible Enterococcus faecalis and E. faecium (MIC90, 0.06 and 0.12
      microg/ml, respectively); however, VRE strains showed decreased dalbavancin
      susceptibility (MIC50, 4 or 8 microg/ml). All streptococcal isolates were
      inhibited at < or =0.25 microg/ml of dalbavancin. This reported dalbavancin
      activity indicates that the new glycopeptide has significant activity, superior
      to available agents in the class, and a potency that was uniform across
      geographically sampled organisms. Some VRE were inhibited by very low dalbavancin
      concentrations (< or = 1 microg/ml; Van B phenotypes). Further clinical
      development seems warranted for this once-weekly administered agent.

PMID- 14972385
TI  - Evaluation of a near-patient fecal antigen test for the assessment of
      Helicobacter pylori status.
AB  - The assessment of Helicobacter pylori antigen in stool specimens is widely
      accepted. Recently a immunochromatographic near-patient test assay has been
      developed. In this first evaluation in 100 patients before and after H. pylori
      eradication therapy we observed a sensitivity (76%) and specificity (98%) of this
      near-patient test.

PMID- 14972386
TI  - Rapid and simple differentiation of C. dubliniensis from C. albicans.
AB  - Differentiation of Candida dubliniensis from C. albicans using biochemical
      methods is time consuming and may be difficult to achieve because of ambiguous
      results. Here, we describe a simple, rapid and inexpensive method for unequivocal
      differentiation of C. dubliniensis from C. albicans using polymerase chain
      reaction (PCR)/RFLP.

PMID- 14972387
TI  - Reduced susceptibility effects in perfusion fMRI with single-shot spin-echo EPI
      acquisitions at 1.5 Tesla.
AB  - Arterial spin labeling (ASL) perfusion contrast is not based on susceptibility
      effects and can therefore be used to study brain function in regions of high
      static inhomogeneity. As a proof of concept, single-shot spin-echo echo-planar
      imaging (EPI) acquisition was carried out with a multislice continuous ASL (CASL)
      method at 1.5T. A bilateral finger tapping paradigm was used in the presence of
      an exogenously induced susceptibility artifact over left motor cortex. The spin
      echo CASL technique was compared with a regular gradient-echo EPI sequence with
      the same slice thickness, as well as other imaging methods using thin slices and
      spin-echo acquisitions. The results demonstrate improved functional sensitivity
      and efficiency of the spin-echo CASL approach as compared with gradient-echo EPI
      techniques, and a trend of improved sensitivity as compared with spin-echo EPI
      approach in the brain regions affected by the susceptibility artifact. ASL
      images, either with or without subtraction of the control, provide a robust
      alternative to blood oxygenation level dependant (BOLD) methods for activation
      imaging in regions of high static field inhomogeneity.

PMID- 14972388
TI  - Cardiac-induced physiologic noise in tissue is a direct observation of cardiac
      induced fluctuations.
AB  - Recent studies have shown that in certain cases, cardiac and respiratory rate
      fluctuations in BOLD-weighted MRI time courses may be an artifact unique to rapid
      sampled acquisitions and may not be present in longer repetition-time
      acquisitions. The implication of this is that, in these cases, cardiac and
      respiratory rate fluctuations are not aliased into data that undersample these
      effects and do not affect the resulting time course measurements. In this study,
      we show that these cases are specific to regions of large cerebrospinal fluid
      content and are not generally true for gray matter regions of the brain. We
      demonstrate that in many brain regions of interest, these fluctuations are
      directly observed as BOLD fluctuations and thus will affect measurements that
      undersample these effects.

PMID- 14972389
TI  - Cavernous hemangiomas in patients with chronic liver disease: MR imaging
      findings.
AB  - The purpose of our study was to assess the difference in magnetic resonance
      imaging (MRI) features of cavernous hemangiomas in patients with chronic liver
      disease compared them with hemangiomas in normal livers. We retrospectively
      searched our records of MRI of the liver between October 1998 and June 2002, and
      identified 76 hemangiomas in 49 patients (18 men and 31 women; age range 29-81
      years [mean, 57 years]). Hemangiomas were classified into 3 groups: patients with
      cirrhosis [group 1, 8 lesions in 8 patients], patients with chronic hepatitis
      [group 2, 6 lesions in 5 patients], and patients without underlying liver disease
      [group 3, 62 lesions in 36 patients]. Four radiologists, blinded to clinical
      information, retrospectively reviewed in consensus the MRI findings of
      hemangiomas for number, size, signal intensities on T1- and T2-weighted images,
      and enhancement patterns on early- and late-phase postcontrast images. The mean
      lesion numbers and sizes were 1.0 and 16.2 +/- 9.6 mm, 1.2 and 15.3 +/- 7.1 mm,
      and 1.7 and 26.1 +/- 24.7 mm in groups 1-3, respectively. There was a correlation
      (p < 0.05, coefficient: 0.35) between lesion number and severity of liver
      disease. Although there was no significant difference in lesion size among the 3
      groups, all of 11 lesions larger than 4 cm in diameter belonged to group 3.
      Almost all lesions appeared moderately hypointense on T1-weighted images and
      moderately hyperintense on T2-weighted images. Twenty-seven lesions showed
      immediate homogeneous enhancement (pattern 1), and 49 showed peripheral nodular
      enhancement with centripetal enhancement progression (pattern 2). There was no
      difference in frequency of enhancement patterns among the 3 groups. Hemangiomas
      were more often solitary in livers with chronic liver disease, large lesions were
      exclusively seen in livers without chronic liver disease, and there was a trend
      for small lesions in patients with chronic liver disease.

PMID- 14972390
TI  - Abdominal imaging studies: comparison of diagnostic accuracies resulting from
      ultrasound, computed tomography, and magnetic resonance imaging in the same
      individual.
AB  - We retrospectively compared the diagnostic accuracy of abdominal ultrasound (US),
      computed tomography (CT), and magnetic resonance imaging (MRI) studies performed
      on the same individual to determine the relative performance of these modalities
      in the evaluation of disease processes, arising from different intra-abdominal
      organ systems. We retrospectively reviewed all procedure codes accrued by our
      abdominal imaging section during a 1-year period to determine how many patients
      underwent all three imaging procedures in our institution within a 2-week
      interval. These cases were then further evaluated to determine: (1) the primary
      organ system of disease involvement, (2) the final diagnosis, and (3) the imaging
      modality that provided the most accurate information upon which appropriate
      medical management was based. Imaging findings were determined by review of
      diagnostic reports, and medical management was determined by chart review. Two
      thousand six hundred-ninety five patients underwent ultrasound, 4,394 patients
      underwent CT, and 872 patients underwent MRI for the investigation of abdominal
      disease. Among these 5,126 patients, 26 underwent sequential US, CT, and MRI
      evaluation within a two-week interval. Appropriate clinical management was based
      on the US findings in 12/26 cases (46%; 95% CI: 27-67%), CT findings in 16/26
      cases (62%; 95% CI: 41-80%), and MRI findings in 24 cases (92%; 95% CI: 75-99%).
      Significant differences in directing appropriate clinical management were found
      when comparing the relative diagnostic accuracies of MRI to US (p = 0.0003) and
      MRI to CT (p = 0.009). However, differences were not significant when comparing
      CT to US (p = 0.27). All final diagnoses in a given patient were accurately
      determined by US in 7/26 cases (27%), by CT in 10/26 cases (38%), and by MRI in
      23/26 cases (88%). When analyzed according to individual diagnoses (61 total), US
      detected 33 of 61 (54%) abnormalities, CT detected 41 (67%) abnormalities, and
      MRI detected 51 (84%) abnormalities. US correctly characterized 32 (52%)
      abnormalities, CT correctly characterized 36 (59%) abnormalities, and MRI
      correctly characterized 49 (80%) abnormalities. Ultrasound, CT, and MR imaging
      correctly diagnosed the disease process in 3 of 12 (25%), 3 of 12 (25%), and 10
      of 12 (83%) patients, respectively, with liver disease; 2 of 9 (22%), 6 of 9
      (66%), and 9 of 9 (100%) patients, respectively, with pancreatic disease; 17 of
      17 (100%), 8 of 17 (47%), and 10 of 17 (58%) patients, respectively, with
      gallbladder and biliary disease; 2 of 8 (25%), 5 of 8 (63%), and 5 of 8 (63%)
      patients, respectively, with renal disease; 0 of 3 (0%), 2 of 3 (66%), and 3 of 3
      (100%) patients, respectively, with adrenal disease; and 8 of 12 (75%), 12 of 12
      (100%), and 12 of 12 (100%) patients with free intraperitoneal fluid. Our results
      provide new information, regarding the relative benefits of ultrasound, CT, and
      MRI for the investigation of abdominal diseases at our institution. This initial
      data suggests that ultrasound provides the most accurate diagnoses in the
      investigation of gallbladder disease; MRI provides the most accurate diagnoses in
      the investigation of hepatic, adrenal, and pancreatic disease; and either CT or
      MRI may be the most appropriate first imaging study for the detection of renal
      disease.

PMID- 14972391
TI  - Enlarged endolymphatic duct and sac syndrome: relationship between MR findings
      and genotype of mutation in Pendred syndrome gene.
AB  - Pendred syndrome (PDS) is characterized by profound deafness in childhood,
      positive perchlorate challenge, and goiter. PDS is often associated with enlarged
      endolymphatic duct and sac (EEDS), and recently, PDS gene mutations have been
      reported even in those patients with EEDS without classic Pendred syndrome. In a
      previous report, the number of mutant alleles was correlated with the degree of
      subclinical thyroid abnormality, but not with hearing loss, in patients with
      missense mutation H723R. It also has been reported that the hearing loss in EEDS
      was not correlated with the EEDS volume, cochlear modiolar area, or signal
      intensity of the endolymphatic sac. We evaluated the correlations between the
      number of mutant alleles and these parameters in patients with EEDS to
      investigate the mechanisms underlying this condition. The study group was
      comprised of 16 Japanese patients with EEDS diagnosed by MR imaging. The H723R
      mutation was homozygous in six patients and heterozygous in six patients, with no
      mutation found in four patients. The modiolar area, EEDS volume, and signal
      intensity ratio (sac signal/cerebrospinal fluid signal) were not significantly
      correlated with the number of mutant alleles. PDS gene mutations may not be the
      only cause of EEDS, and the mechanisms underlying EEDS remain unclear.

PMID- 14972392
TI  - MRI characterization of residual mediastinal masses in Hodgkin's disease: long
      term follow-up.
AB  - Our purpose was to evaluate the role of MRI in distinguishing fibrous from active
      residual masses in treated Hodgkin's disease. Forty patients with residual
      mediastinal mass larger than 1.5 cm underwent MRI 1, 3, 6, and 12 months after
      the end of cycles of prescribed chemotherapy or combined chemoradiotherapy. The
      MRI examinations were performed on a 0.5 and a 1.5 T systems, using T(1) before
      and after gadolinium injection and T(2)-weighted sequences. Each time the
      residual mass was evaluated in size and signal intensity on spin echo (SE) T(2)
      weighted images and on SE T(1)-weighted images after contrast medium. Low signal
      intensity and low contrast enhancement were considered signs of inactive
      residues; homogeneous high signal intensity and high contrast enhancement were
      indicative of active residual disease; heterogeneous signal intensity and
      heterogeneous contrast enhancement were indicative of partial remission or
      necrotic/inflammatory phenomena. MR showed high diagnostic accuracy in the
      evaluation of Hodgkin's mediastinal residues after treatment, if performed at
      least 6 months after the end of therapy, reaching the highest sensitivity and
      specificity values at 12 month follow-up (considering the three parameters-T(2)
      signal intensity, contrast-enhancement, and size-all together). If we consider
      the single parameters individually, we can observe that size variation remains
      the more valuable parameter to predict or to exclude a relapse. MR diagnostic
      accuracy at the 6-month follow-up was lower due to the higher incidence of
      inhomogeneous pattern. The accuracy of MR performed at 1 and at 3 months after
      the end of therapy was not satisfying. This represents a clinical problem because
      the most important clinical decisions have to be taken just in this early post
      treatment phase.

PMID- 14972393
TI  - Diffusion characteristics of large molecules assessed by proton MRS on a whole
      body MR system.
AB  - Methods for examinations of diffusion of large molecules of the size of fatty
      acids or triglycerides were developed for whole body MR units. Samples of
      aliphatic molecules were examined to study the influence of chain length.
      Feasibility under in vivo conditions was tested on lard samples at 37 degrees C
      and on human subjects Three stimulated echo sequences with maximum b-values of
      2000 s/mm(2), 20000 s/mm(2), and 80000 s/mm(2) were used to assess a wide range
      of mobility. Sequence timing was optimized to minimize relaxation losses of fatty
      tissue. Apparent diffusion coefficients (ADC) were determined from five spectra
      with different diffusion weighting. In-vitro experiments were performed on
      butanol, decanol, and oleic acid to study the influence of chain length. In vivo
      conditions were mimicked using lard at 37 degrees C representing a composition of
      substances of various chain lengths. Subcutaneous fat and tibial bone marrow were
      studied in three healthy volunteers. ADC of muscular lipids of the lower leg was
      determined in two subjects. ADC values of pure aliphatic substances were in the
      range between 3.2 x 10(-5) mm(2)/s for oleic acid and 37.8 x 10(-5) mm(2)/s for
      butanol. In vivo investigations revealed ADC values of 1.11-1.24 x 10(-5) mm(2)/s
      for tibial bone marrow and 1.21-2.05 x 10(-5) mm(2)/s for subcutaneous fat.
      Diffusion coefficients of extra- and intramyocellular lipids were 1.83-3.65 x 10(
      5) mm(2)/s and 2.22-3.60 x 10(-5) mm(2)/s, respectively. The proposed technique
      enables determination of ADC values of relatively large molecules and of lipid
      tissue compartments under in vivo conditions. Diffusion properties in several
      human lipid compartments are reported for the first time. Incoherent voxel motion
      influences the in vivo results to an unknown degree because of high motion
      sensitivity. In vitro experiments revealed ADC values depending on the chain
      length of the substances, indicating a residual dependence of measured ADC's on
      sequence timing.

PMID- 14972394
TI  - A numerical approach to the selection of basis for frame-encoded MRI.
AB  - A numerical approach was proposed to systematically investigating the suitability
      of various bases for frame-encoded magnetic resonance imaging (MRI). Several
      basic requirements were established for the ideal encoding frame basis. Three
      different orders of spline bases were extensively examined with simulation of 2
      dimensional MRI. Analyses of imaging time and signal-to-noise ratio showed that
      the compactly supported quadratic spline basis is a strong candidate for high
      quality MRI with a short imaging time. The simulations also suggested that
      encoding with three levels of resolution is the best choice.

PMID- 14972395
TI  - Affine registration: a comparison of several programs.
AB  - Several registration programs with an affine model for the displacement field
      were tested on various 2D and 3D MRI of the same modality. The following programs
      were considered: AIR 3.0 (Woods, J. Comp. Assist. Tomogr, 22(1): 139-152, 1998),
      COCGV (Ostuni, JMRI, 7(2): 410-415, 1997), FLIRT (Jenkinson, Med. Image Analysis,
      5(2): 143-156, 2001), Intramodal Registration (Thevenaz, IEEE Trans. Image Proc.,
      7(1): 27-41, 1998), SPM (Friston, Human Brain Mapping, 2: 165-189, 1995), and
      Patch Algorithm (Zhilkin, MRI 18(9): 1143-1150, 2000). Although some of these
      programs can perform multimodal registration, none was used in such a mode. This
      paper attempts a fair comparison of the performance of the Patch Algorithm with
      other programs. However, different settings of the programs' parameters may
      further improve the quality of the registration and/or change execution speed.
      The registered images, the CPU time required to perform the registration, and the
      error between the registered and reference images, are presented. Most of the
      programs give comparable accuracies of registration, but their execution times
      vary considerably. In general the AIR and Patch Algorithm require the least time.
      The Patch Algorithm can be easily parallelizable on a multi-processor computer.

PMID- 14972396
TI  - Optimisation of T2 and M0 measurements of bi-exponential systems.
AB  - Cramer-Rao theory and computer simulations were used to show that the errors
      involved in calculating the magnetization and relaxation parameters of a two
      component system decrease with: (1) increasing SNR, (2) increasing number of
      echoes used in the fitting procedure, and (3) increasing ratio of the relaxation
      times of the two components, T(22)/T(21). Images of bi-compartmental phantoms of
      known T(2) values were acquired using an optimized imaging sequence, and an
      optimized fitting algorithm was used to calculate the T(2) values of the two
      components by fitting the resulting images to a bi-exponential decay model.
      Accuracy better than 6% was achieved in the calculations of the T(2) values of
      the two components, and region fitting provided better accuracy than pixel-by
      pixel fitting. The procedures were used to calculate the T(2) and M(0) values of
      equine carpal bones with known degree of radiographic bone sclerosis. Although
      the T(2) and M(0) values of both water and fat components all decreased with the
      degree of radiographic bone sclerosis, the transverse relaxation of the water
      component, T(2W), showed a greater decrease with advanced stages of bone
      sclerosis.

PMID- 14972397
TI  - Influence of MRI acquisition protocols and image intensity normalization methods
      on texture classification.
AB  - Texture analysis methods quantify the spatial variations in gray level values
      within an image and thus can provide useful information on the structures
      observed. However, they are sensitive to acquisition conditions due to the use of
      different protocols and to intra- and interscanner variations in the case of MRI.
      The influence was studied of two protocols and four different conditions of
      normalization of gray levels on the discrimination power of texture analysis
      methods applied to soft cheeses. Thirty-two samples of soft cheese were chosen at
      two different ripening periods (16 young and 16 old samples) in order to obtain
      two different microscopic structures of the protein gel. Proton density and T(2)
      weighted MR images were acquired using a spin echo sequence on a 0.2 T scanner.
      Gray levels were normalized according to four methods: original gray levels, same
      maximum for all images, same mean for all images, and dynamics limited to micro
      +/- 3sigma. Regions of interest were automatically defined, and texture
      descriptors were then computed for the co-occurrence matrix, run length matrix,
      gradient matrix, autoregressive model, and wavelet transform. The features with
      the lowest probability of error and average correlation coefficient were selected
      and used for classification with 1-nearest neighbor (1-NN) classifier. The best
      results were obtained when using the limitation of dynamics to micro +/- 3sigma,
      which enhanced the differences between the two classes. The results demonstrated
      the influence of the normalization method and of the acquisition protocol on the
      effectiveness of the classification and also on the parameters selected for
      classification. These results indicate the need to evaluate sensitivity to MR
      acquisition protocols and to gray level normalization methods when texture
      analysis is required.

PMID- 14972398
TI  - Multicenter trial for the set-up of a MRI quality assurance programme.
AB  - Many international protocols related to RMI-QC program are focused on acquisition
      methods and analysis of several image quality parameters but rarely normality
      ranges or measurement frequencies are presented. To address this problem we
      investigated the variability of many magnetic resonance imaging (MRI) systems
      with the set-up of multicenter trial. The trial was set up to investigate short
      and mid-term variability of two fundamental nongeometric image quality
      parameters: signal-to-noise (SNR) and integral percent uniformity (U%). Ten
      centers (12 devices) participated to data collection consisting of a three-step
      protocol. First, 10 consecutive images of a phantom were collected with a spin
      echo sequence. As second step the series collection was repeated 24 h later.
      Finally a single image acquisition was performed twice a week for 5 weeks. The
      analysis of results allowed us to define a "physiological" variability of +/-3%
      of the reference level for both parameters and to conclude that a weekly
      measurement is adequate to detect relevant variations of device performance.

PMID- 14972399
TI  - In vivo GABA detection with improved selectivity and sensitivity by localized
      double quantum filter technique at 4.1T.
AB  - Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter for the
      normal function of mammal and human brain. It is difficult to detect GABA signal
      with the conventional single quantum technique due to its relatively low
      concentration and overlapping with other signals from creatine (Cr), glutathione
      (GSH), as well as macromolecules. Using a high-selective read pulse, DANTE, and
      at the facility of increased sensitivity and chemical shift resolution at high
      field 4.1T, GABA editing by double quantum filter (DQF) with robust suppression
      of Cr and GSH was achieved. Our editing efficiency of 40-50% was achievable on a
      GABA phantom (50 mM GABA and 61 mM choline). Furthermore, GABA editing spectra
      were acquired with echo time TE = 77 ms, and any possible macromolecular
      contamination to GABA editing spectra was found to be negligible. This high-field
      DQF setup was applied to 11 healthy volunteers, and the mean GABA level was
      measured to be 1.12 +/- 0.15 mM in the occipital lobe in reference to 7.1 mM Cr
      concentration.

PMID- 14972400
TI  - High-energy phosphate metabolism during incremental calf exercise in humans
      measured by 31 phosphorus magnetic resonance spectroscopy (31P MRS).
AB  - Several previous 31 phosphorus magnetic resonance spectroscopy ((31)P MRS)
      studies performing incremental or progressive muscle exercises have observed that
      a decrease in pH is accompanied with an acceleration in phosphocreatine (PCr)
      hydrolysis. The purpose of this study was to investigate the relationship between
      PCr breakdown and pH during isotonic, exhaustive, incremental plantar flexion
      exercises. We included eight healthy, male volunteers into this study. Using a
      1.5 Tesla MR scanner and a self-built exercise bench, we performed serial free
      induction decay (FID) (31)P MRS measurements with a time resolution of 1 min at
      rest, isotonic calf muscle exercise, and recovery. The exercise protocol
      consisted of 5-min intervals with 4.5, 6, 7.5, and 9 W workload followed by 9-min
      recovery. Changes in PCr and inorganic phosphate (Pi) were determined as percent
      changes in comparison to the baseline. In addition, pH values were calculated.
      This study obtained significant decreases in PCr corresponding to the gradual
      increases in workload. In each workload level that was succeeded by all
      volunteers, PCr hydrolysis passed into a steady state. After an early biphasic
      response, we detected a significant decrease in pH from the first to the second
      minute of the 6-W workload level followed by a further continuous decrease in pH
      up to the second minute of the recovery phase. The decrease in pH was not
      accompanied by acceleration in PCr hydrolysis. In conclusion, this study shows
      that PCr hydrolysis during incremental plantar flexion exercises passes into a
      steady state at different workload levels. The observed decrease in pH does not
      result in acceleration of PCr hydrolysis.

PMID- 14972401
TI  - 7Li MR measures of blood lithium--correlation with chemical analysis data.
AB  - Lithium is used in the treatment and prophylaxis of manic-depressive illness. A
      narrow therapeutic range of lithium (0.4-1.2 meq/l) requires constant monitoring
      of these levels to avoid neurotoxicity and overdose. It is general practice to
      measure plasma lithium levels as a guide to monitor the therapy. Efforts to
      predict the concentration of Li at its active sites in the brain have led to the
      use of red blood cells (RBCs) because they are similar to neuronal cells. Thus
      RBC lithium is a very relevant clinical parameter for monitoring therapy and to
      observe the changes at intracellular levels under varying treatment conditions. A
      measure of both plasma and RBC lithium may be of significant value to physicians
      and researchers as lithium profile for RBCs correlate more closely with the brain
      lithium than plasma lithium. Although methods to measure lithium in blood such as
      atomic absorption or flame photometry exist, a complete quantitation of both
      plasma and RBC lithium requires a tedious physical separation of the two
      components prior to chemical analysis. On the other hand, lithium MR technique,
      via the use of shift reagents, can provide both plasma and RBC lithium in a
      single study. Here we have performed a correlation study of lithium results
      obtained from MR with the vitros dry-slide method on blood samples from rats
      treated with lithium. The results show a high degree of correlation between the
      two methods. Additionally, the MR measurements made on dilute samples of blood
      indicate that small blood samples with lithium concentration in the neighborhood
      of 0.08 meq/l can be measured with high accuracy and reproducibility needed for
      clinical purposes.

PMID- 14972402
TI  - Application of MRI to monitor the process of ripening and decay in citrus treated
      with chitosan solutions.
AB  - Chitosan is a biopolymer, which has numerous applications in agriculture and
      agroindustries. Coating fruit and vegetables with chitosan has some positive
      advantages for the long-term storage of foods, because the film of chitosan
      provides a kind of an active package, which allows a gradual release of
      preservatives, thus inhibiting fungal growth and maintaining the external
      appearance of the fruit for a longer time In this study, two varieties of citrus,
      Fortune mandarins and Valencia oranges were coated with Biorend(R) (IDEBIO S.L.,
      Salamanca, Spain) (a compound whose active molecule is chitosan), to investigate
      its effect on maturity, decay, and damage, and therefore, to find a better method
      for the long term storage of fruit. The effect of chitosan as a fungistatic was
      also studied. To that end, the fruit was maintained in a damp storage room, ideal
      conditions for the growth of fungi. The magnetic resonance imaging (MRI)
      technique was used to monitor the process of ripening and decay in the citrus
      fruit that had been coated with chitosan. The dissolution of the chitosan on the
      mandarins and oranges produced excellent results in terms of percentage of weight
      loss, MRI, and visual appearance.

PMID- 14972408
TI  - A case study of radon-222 transport from continental North-East Asia to the
      Japanese islands in winter by numerical analysis.
AB  - A case study of the regional transport ( approximately 3000 km) of radon-222
      ((222)Rn) from continental North-East Asia to the Japanese islands was performed
      by numerical analysis using five separate source areas (South, Middle and North
      China, Russia and Korea), while a seasonal northwest wind blew over the Japan
      Sea. The results for three periods (Term I: 16-18, Term II: 22-25 and Term III:
      27-28 in December 1990) were compared with concentrations measured at the
      Kanazawa site (near the coast of the Japan Sea facing the seasonal wind) and the
      Nagoya site (overland and downwind on the shores of the Pacific Ocean). Most of
      the (222)Rn at the Kanazawa site was calculated to come from North China and
      Korea in Term I, Middle China, North China, and Korea in Term II, and Russia and
      Korea in Term III. The considerable differences in the origins of (222)Rn
      emanated from the continent were estimated between Terms I, II and III, even
      though the similar northwest wind was dominant over the Japan Sea. A contour line
      analysis indicated movement of (222)Rn emanated from Middle China in a northerly
      direction first and then a southeasterly direction, resulting from low pressure.
      The results suggest that the low-pressure systems play an important role in the
      transport of (222)Rn in North-East Asia.

PMID- 14972409
TI  - Concentration measurements of 7Be at ground level air at Palermo, Italy
      comparison with solar activity over a period of 21 years.
AB  - Air activity concentrations of (7)Be in Palermo determined for the period January
      1995-December 2002 by gamma-ray spectrometric analysis of particulate samples
      collected on paper filter by a high-volume sampler (approximately 900 m(3) h(-1))
      are reported. The temporal behaviour of (7)Be concentration presents the same
      characteristics already observed in the measurements carried out over the
      previous 13-year (1982-1994) investigated period. The mean value of 5.06 mBq m(
      3) obtained from the analysis of the 4636 particulate samples collected from 1982
      to 2002 can be considered a representative value of (7)Be air concentration at
      ground level in our geographical zone. The comparison of long-term variation in
      the (7)Be concentrations with the cyclic solar activity-extended to the whole
      period of 21 years-confirms the inverse correlation between the two quantities.

PMID- 14972410
TI  - Importance of colloids in the transport within the dissolved phase (<450 nm) of
      artificial radionuclides from the Rhone river towards the Gulf of Lions
      (Mediterranean Sea).
AB  - The significance of colloidal fractions regarding the transport of artificial
      radionuclides in natural water systems is underlined by using sequential
      ultrafiltration both in the Rhone freshwater and the marine area under and
      outside the influence of the river outflow. Indeed, the Rhodanian aquatic system
      represents an interesting test site as various artificial radionuclides are
      released into the Rhone river by several nuclear installations. We focused our
      study on (137)Cs, (106)Ru, (60)Co, (238)Pu and (239+240)Pu. Our results show that
      Fe, Al and Organic carbon (OC) are the main components of colloidal matter.
      Colloids represent about 15% of dissolved (<450 nm) OC and 25% of dissolved Fe
      and Al exported towards the sea. Within the dissolved (< 450 nm) phase, these
      colloidal compounds are shown to account for the transport of 40% for both Co and
      Ru, 60% for (238)Pu and (239+240)Pu and have no significance on (137)Cs flux.

PMID- 14972411
TI  - 90Sr, 238U, 234U, 137Cs, 40K and 239/240Pu in Emmental type cheese produced in
      different regions of Western Europe.
AB  - A method is presented for the determination of (90)Sr and uranium in Emmental
      type cheese collected in dairy plants from different European countries. Results
      display a significant correlation (r = 0.708 Student t-test = 6.02) between the
      (90)Sr content of the cheese and the altitude of grazing. The highest (90)Sr
      activity is 1.13 Bq kg(-1) of cheese and the lowest is 0.29 Bq kg(-1). Uranium
      activity is very low with a highest (238)U value of 27 mBq kg(-1). In addition,
      (234)U/(238)U ratio shows a large enrichment in (234)U for every location.
      Without any significant indication of the geographic origin of the cheese, this
      enrichment is believed to be due to the geological features of the pasture, soil
      and underground water. These results tend to prove that the contamination of milk
      by uranium originates principally from the water that the cows drink instead of
      the forage. This finding may have a great importance in models dealing with dairy
      food contamination by radionuclides following a nuclear accident. Also, the
      (90)Sr content and to a lesser extent the (234)U/(238)U ratio could be used to
      trace the authenticity of the origin of the cheese. (137)Cs activity is lower
      than the detection limit of 0.1 Bq kg(-1) in all the samples collected (n = 20).
      Based on natural (40)K activity in cheese (15-21 Bq kg(-1)), the decontamination
      factor for the alkaline cations from milk to cheese is about 20. Plutonium
      activity stays below the detection limit of 0.3 mBq kg(-1).

PMID- 14972412
TI  - Assessment of radiological effects on the regional environment due to the
      operation of the Tokai Reprocessing Plant.
AB  - The regional environmental radiological effects were assessed for the past 25
      year operation of the Tokai Reprocessing Plant (TRP). The assessment was
      basically performed with the environmental radiological monitoring data around
      the TRP. For the environmental monitoring, various kinds of terrestrial and
      marine samples including air dust, surface soil, polished rice grain, leafy
      vegetable, milk, seawater, seabed sediments, fish, shellfish and seaweed were
      collected in the surrounding environment of the TRP. Radionuclides such as (3)H,
      (14)C, (90)Sr, (137)Cs and (239,240)Pu in the environmental samples were
      determined by radiochemical methods. However, they showed no significant short
      term increase or long-term accumulation of radionuclides discharged from the TRP.
      Therefore, the public dose was evaluated using the mathematical models and the
      discharge data of radionuclides. The estimated annual effective dose for the
      public was about 0.1% of the annual effective dose limit recommended by the ICRP.
      The assessment showed that there were no significant radiological effects on the
      environment and the public due to the 25-year operation of the TRP.

PMID- 14972413
TI  - A new method to account for the depth distribution of 137Cs in soils in the
      calculation of external radiation dose-rate.
AB  - This work reports a new method for calculating the external dose-rate as a
      function of height above land that has been contaminated with a surface
      deposition of (137)Cs. Unlike previous work this method accounts for vertical
      migration of (137)Cs using the Advection Dispersion Equation (ADE) with
      appropriate parameters. The results have been successfully verified with field
      measurements from the (137)Cs contaminated regions within the Republic of
      Belarus. The method also correctly predicts the observed variation of dose-rate
      with elevation above the soil surface and it is shown how this method can be used
      to predict the reduction in surface dose-rate after remediation measures such as
      deep ploughing have taken place.

PMID- 14972414
TI  - Kinetics of dissolution of Chernobyl fuel particles in soil in natural
      conditions.
AB  - Kinetic of fuel particles dissolution under natural environmental conditions has
      been investigated using the data on (90)Sr speciation in soils collected from
      1995 to 1997 within the Chernobyl nuclear power plant 50 km zone. The dependency
      of fuel particles dissolution constants on the soil acidity (pH = 4-7) has been
      obtained on the basis of large and statistically reliable experimental data.
      Results show that between 2 and 21% of (90)Sr activity is associated with
      weathering resistant fuel particles. Therefore, these particles would not
      influence the radiological situation in the near future. The map of the main
      agrochemical characteristics and the map of the fuel particles dissolution
      constants have been created for the 30-km zone territory. According to the
      prognosis of dynamics of fuel particles dissolution in the investigated zone, a
      radiological situation along the fuel paths of radioactive fallout in present
      time reached a stable state. An increasing in absolute contents of (90)Sr mobile
      forms in neutral soils will be observed in the next 10-20 yr. However, the
      difference between the maximum level of mobile forms contents and their existing
      contents will not exceed 20%.

PMID- 14972415
TI  - Plutonium concentrations in waters from the southern Baltic Sea and their
      distribution in cod (Gadus morhua) skin and gills.
AB  - The concentrations of (238)Pu and (239+240)Pu in water samples and suspended
      particulate fractions, as well as in colloidal fraction from the southern Baltic
      Sea are presented. The (239+240)Pu concentration in surface seawater samples fall
      within range from 5.2 mBq.m(-3) for Gdansk Bay to 150 mBq.m(-3) for Pomeranian
      Bay, most of which (from 52 to 96%) constituted filterable forms (</=0.45
      microm). Also the distribution of plutonium in parts of cod gills and skin are
      presented and discussed. Over 60% of the plutonium in cod gills is accumulated in
      the gill arch, which suggests its metabolic origin. Most of plutonium associated
      with skin is in mucus, which suggests its adsorption from water.

PMID- 14972416
TI  - Aortic stenosis: even mild disease is significant.

PMID- 14972417
TI  - Prevention of contrast-induced renal dysfunction by N-acetylcysteine. Truth or
      myth?

PMID- 14972418
TI  - Percutaneous coronary intervention in diabetic patients with non-ST-segment
      elevation acute coronary syndromes.
AB  - Key pathophysiologic mechanisms of diabetes-related coronary disease include
      inflammation and a prothrombotic state. In the setting of non-ST-segment
      elevation acute coronary syndromes diabetic patients are at high risk for
      subsequent cardiovascular events. At the same time, they derive greater benefit
      than non-diabetic counterparts from aggressive antithrombotic therapy, early
      coronary angiography, and stent-based percutaneous coronary intervention. The
      mainstays of antithrombotic therapy for diabetic patients undergoing percutaneous
      revascularization include aspirin, clopidogrel, platelet glycoprotein IIb/IIIa
      receptor antagonists, and heparin or low-molecular-weight heparin. Despite
      dramatic reduction in restenosis conferred by drug-eluting stents, diabetic
      patients remain at increased risk for repeat revascularization. More efforts are
      needed both in terms of local drug elution as well as systemic pharmacologic
      therapies to further contain the excessive neointimal proliferation that
      characterizes the diabetic response to vascular injury.

PMID- 14972419
TI  - Mild and moderate aortic stenosis. Natural history and risk stratification by
      echocardiography.
AB  - AIMS: To define the natural history and predictors of outcome in mild and
      moderate aortic stenosis (AS). METHODS AND RESULTS: One hundred and seventy-six
      consecutive asymptomatic patients (73 women, age 58+/-19 years) with mild to
      moderate AS (jet velocity 2.5 to 3.9m/s) were followed for 48+/-19 months.
      Haemodynamic progression and clinical outcome was analysed. Event-free survival
      with end-points defined as death (n=34) or aortic valve surgery (n=33), was 95+/
      2%, 75+/-3% and 60+/-5% at 1, 3 and 5 years, respectively. Both, cardiac and non
      cardiac mortality were significantly increased, resulting in a 1.8 times higher
      mortality than expected (P<0.005). By multivariate analysis, moderate to severe
      aortic valve calcification, coronary artery disease (CAD) and peak jet velocity
      were independent predictors of outcome. Event-free survival for patients with
      moderate or severe valve calcification was 92+/-4%, 61+/-7% and 42+/-7% at 1, 3
      and 5 years versus 100%, 90+/-4% and 82+/-5% for patients with no or mild
      calcification. Patients with calcified aortic valves, CAD or with an event had a
      significantly faster haemodynamic progression. Of 129 patients with a follow-up
      echocardiographic exam, 59 (46%) developed severe stenosis during follow-up.
      CONCLUSION: Outcome of mild and moderate AS is worse than commonly assumed. Rapid
      progression and excess mortality have to be considered. Significant valve
      calcification, CAD and rapid progression of aortic jet velocity indicate poor
      outcome. Patients with these characteristics may require closer follow-up than
      generally assumed.

PMID- 14972420
TI  - Standard vs double dose of N-acetylcysteine to prevent contrast agent associated
      nephrotoxicity.
AB  - AIMS: Prophylactic administration of N-acetylcysteine (NAC) (600mg orally twice
      daily), along with hydration, prevents contrast agent-associated nephrotoxicity
      (CAN) induced by a low dose of non-ionic, low-osmolality contrast dye. We tested
      whether a double dose of NAC is more effective to prevent CAN. METHODS AND
      RESULTS: Two-hundred-twenty-four consecutive patients with chronic renal
      insufficiency (creatinine level > or =1.5mg/dl and/or creatinine clearance
      <60ml/min), referred to our institution for coronary and/or peripheral
      procedures, were randomly assigned to receive 0.45% saline intravenously and NAC
      at the standard dose (600mg orally twice daily; SD Group; n=110) or at a double
      dose (1200mg orally twice daily; DD Group; n=114) before and after a non-ionic,
      low-osmolality contrast dye administration. Increase of at least 0.5mg/dl of the
      creatinine concentration 48h after the procedure occurred in 12/109 patients
      (11%) in the SD Group and 4/114 patients (3.5%) in the DD Group (P=0.038;
      OR=0.29; 95% CI=0.09-0.94). In the subgroup with low (<140ml, or contrast ratio
      <=1) contrast dose, no significant difference in renal function deterioration
      occurred between the 2 groups. In the subgroup with high (> or =140ml, or
      contrast ratio >1) contrast dose, the event was significantly more frequent in
      the SD Group. Conclusions Double dose of NAC seems to be more effective than the
      standard dose in preventing CAN, especially with high volumes of non-ionic, low
      osmolality contrast agent.

PMID- 14972421
TI  - Oral acetylcysteine as an adjunct to saline hydration for the prevention of
      contrast-induced nephropathy following coronary angiography. A randomized
      controlled trial and review of the current literature.
AB  - AIMS: To determine laboratory and clinical benefit of oral acetylcysteine, as an
      adjunct to saline hydration, in chronic renal insufficiency patients undergoing
      coronary angiography. METHODS AND RESULTS: We prospectively studied 80 patients
      with chronic renal insufficiency (mean [+/-SD] serum creatinine concentration
      2.0+/-0.39mg/dl), who underwent coronary angiography with or without
      intervention. Patients were randomly assigned to receive either acetylcysteine
      (600mg orally t.i.d.) or placebo, in addition to intravenous 0.45% saline (1ml/kg
      of body weight per hour), 12h prior to and after coronary angiography. There was
      an increase of >/=0.5mg/dl in the serum creatinine concentration 48h after
      coronary angiography in seven of the 80 patients (9%): in four of the 41 patients
      (10%) in the acetylcysteine group and in three of the 39 patients (8%) in the
      placebo group (P=0.52). The incidence of in-hospital adverse clinical events
      (acetylcysteine, 5% vs placebo, 8%, P=0.47) and the length of hospital stay
      [acetylcysteine, median (interquartile range) 4 (2-4) days vs placebo, 2 (2-4)
      days, P=0.44] did not differ significantly between the two treatment groups.
      CONCLUSION: Our findings do not support routine prophylactic administration of
      oral acetylcysteine as an adjunct to saline hydration for the prevention of
      contrast-induced nephropathy in chronic renal insufficiency patients undergoing
      coronary angiography.

PMID- 14972422
TI  - Validation of coronary flow reserve measurements by thermodilution in clinical
      practice.
AB  - BACKGROUND: Coronary flow reserve (CFR) and fractional flow reserve (FFR) provide
      complementary information on the coronary circulation. Using a pressure wire, it
      is possible to calculate CFR by thermodilution (CFR(thermo)), so that FFR and CFR
      can be measured with a single guide wire. The present multicentric study was
      performed to compare the feasibility of CFR(thermo)obtained with an improved
      algorithm and a standardized injection technique and its agreement with Doppler
      derived CFR (CFR(Doppler)). METHODS AND RESULTS: In 86 patients with coronary
      artery disease recruited during 1 week in eight centres FFR, CFR(thermo)and
      CFR(Doppler)were measured. FFR could be obtained in all patients (100%). An
      optimal CFR(Doppler)could be obtained in 69% of the patients. CFR(thermo)could be
      obtained in 97% of the patients. A significant correlation was found between
      CFR(Doppler)and CFR(thermo)(r=0.79, P<0.0001) but CFR(thermo)tended to be higher
      than CFR(Doppler). CONCLUSIONS: In a setting close to 'real world' practice, this
      multicentric study confirms the feasibility and reliability of thermodilution
      derived CFR. In addition, the safety and the swiftness of assessing FFR and CFR
      with one single guide wire makes the latter a unique clinical tool for the
      evaluation of the coronary circulation.

PMID- 14972423
TI  - ST segment elevation at 72 hours in patients with a first anterior myocardial
      infarction best correlates with pre-discharge and 1-year regional contractility
      and ventricular dilatation.
AB  - AIMS: To analyse the relationship between the in-hospital course of ST segment
      elevation (STE) and negative T wave (NTW) with ejection fraction, regional
      contractility and left ventricular end-diastolic volume at pre-discharge and at 1
      year in patients with a first anterior STE acute myocardial infarction (AMI).
      METHODS AND RESULTS: ECG changes were measured during hospitalization and at 1
      year whereas ejection fraction, regional contractility score and end-diastolic
      volume index were measured by isotopic ventriculography at pre-discharge and at 1
      year. At 72h but not earlier patients with SigmaSTE >0.6mV (group A, n: 35) had a
      lower ejection fraction (P<0.001), a higher regional contractility score
      (P<0.001) and a larger end-diastolic volume index (P<0.001) at discharge than
      those with <0.6mV (group B, n: 26). Negative T wave did not provide additional
      information. At 1 year, group A continued to show a more impaired ejection
      fraction and regional contractility than group B and a larger end-diastolic
      volume. CONCLUSION: Although reportedly changes in STE within the first hours
      correlate with coronary reperfusion our findings indicate that additional
      assessment of STE as early as at 72h correlates with wall motion, ejection
      fraction and ventricular dilatation at discharge and at 1 year.

PMID- 14972424
TI  - Effect of fixed low-dose warfarin added to aspirin in the long term after acute
      myocardial infarction; the LoWASA Study.
AB  - AIM: To evaluate whether long-term treatment with a fixed low dose of warfarin in
      combination with aspirin improves the prognosis compared with aspirin treatment
      alone after an acute myocardial infarction (AMI). METHODS: Patients who were
      hospitalized for AMI were randomized to either 1.25mg of warfarin plus 75mg of
      aspirin (n=1659) daily or 75mg of aspirin alone (n=1641). The study was performed
      according to the PROBE (Prospective Open Treatment and Blinded End Point
      Evaluation) design and was conducted at 31 hospitals in Sweden. The median follow
      up time was 5.0 years. In the aspirin+warfarin group, 30.2% were permanently
      withdrawn as opposed to 14.0% in the aspirin group (P<0.0001). Analyses were
      performed on an intention-to-treat basis. RESULTS: The combination of
      cardiovascular death, reinfarction or stroke was registered in 28.1% in the
      aspirin+warfarin group versus 28.8% in the aspirin group (NS). Cardiovascular
      deaths occurred in 14.2% in the aspirin+warfarin group vs 15.7% in the aspirin
      group (NS). Whereas no difference was found with regard to total mortality or
      reinfarction, those randomized to aspirin+warfarin had a reduced occurrence of
      stroke (4.7% vs 7.1%; P=0.004). The percentage of patients who suffered a serious
      bleed was 1.0% in the aspirin group vs 2.2% in the combination group (P=0.0006).
      CONCLUSION: A fixed low dose of warfarin added to aspirin in the long term after
      AMI did not reduce the combined risk of cardiovascular death, reinfarction or
      stroke. The results did, however, indicate that a fixed low dose of warfarin
      added to aspirin reduced the risk of stroke, but this was a secondary end point.
      The combination of aspirin and warfarin was associated with an increased risk of
      bleeding.

PMID- 14972425
TI  - Association of oestrogen receptor alpha gene polymorphism with the angiographic
      extent of coronary artery disease.
AB  - AIMS: To investigate the association between sequence variants in the promoter
      region of the oestrogen receptor-alpha (ER-alpha) gene and the angiographic
      severity of coronary artery disease (CAD). METHODS AND RESULTS: We studied 503
      subjects undergoing coronary angiography (mean age 63+/-12 years, 72% men, 28%
      women). Coronary artery disease extent was assessed by the number of: (1) major
      coronary vessels with >50% narrowing (NMCV); (2) coronary vessels with any
      narrowing (NCV); (3) narrowed coronary segments (NCS). The number of thymine and
      adenine dinucleotide repeats [(TA)(n)], 1174 base-pairs upstream exon 1, was
      determined by PCR. The median number of (TA)(n)(18) was used to categorize
      subjects into long, short and mixed allele genotypes. Poisson regression was used
      to analyse the association between genotypes and CAD extent, with age category
      (age #10877;55 vs >55), sex, risk factors and age at onset of CAD as covariates.
      In young subjects, (TA)(n)length had a significant effect on NCS (P=0.047) and a
      borderline significant effect on NCV (P=0.066). Young subjects homozygous for
      long alleles had higher NCV and NCS compared to those homozygous for short
      alleles (NCV 3.7+/-2.4 vs 2.4+/-1.8, NCS 4.4+/-2.7 vs 3.1+/-2.3, respectively,
      P#10877;0.034). CONCLUSION: The (TA)(n)length in the ER-alpha gene promoter
      region is associated with the angiographic severity of CAD in young patients.

PMID- 14972426
TI  - Diagnostic value of abnormal Q waves for identification of preclinical carriers
      of hypertrophic cardiomyopathy based on a molecular genetic diagnosis.
AB  - AIMS: There are currently no established diagnostic criteria for the
      identification of abnormal Q waves in patients with hypertrophic cardiomyopathy
      (HCM), resulting in various definitions being applied in each previous study. The
      aim of this study was to determine the most accurate diagnostic definition of
      abnormal Q waves for HCM based on a molecular genetic diagnosis, and also to
      apply abnormal Q waves to the identification of preclinical carriers. METHODS AND
      RESULTS: We applied three different criteria used in previous reports for
      abnormal Q waves in 148 genotyped subjects. Of the three criteria, Criterion 3 (Q
      wave >3mm in depth and/or >0.04s in duration in at least two leads except aVR)
      showed the highest sensitivity (50% in the young, 29% in adults) while retaining
      a high specificity (90% in the young, 97% in adults), resulting in the highest
      accuracy (69% in the young, 52% in adults). Using Criterion 3, abnormal Q waves
      were present 27.6% of preclinical carriers, and in 5.4% of non-carriers (P<0.01).
      CONCLUSIONS: These findings suggest that Criterion 3 may be the most accurate
      diagnostic definition for HCM. Understanding the diagnostic value of abnormal Q
      waves may be useful in screening preclinical carriers of HCM.

PMID- 14972427
TI  - Tissue plasminogen activator antigen and coronary heart disease. Prospective
      study and meta-analysis.
AB  - AIMS: To determine whether circulating tissue plasminogen activator (t-PA)
      antigen concentrations are prospectively related to risk of coronary heart
      disease (CHD) in the general population. METHODS AND RESULTS: We measured
      baseline concentrations of t-PA antigen in the stored serum samples of 606 CHD
      cases and 1227 controls 'nested' in a prospective cohort of 5661 men monitored
      for 16 years, and conducted a meta-analysis of previous relevant studies to place
      our findings in context. Tissue plasminogen activator antigen values were
      strongly correlated with several vascular risk factors, including serum lipids,
      body mass index, alcohol consumption, and markers of systemic inflammation. In a
      comparison of men in the top third compared with those in the bottom third of
      baseline t-PA antigen values, the odds ratio for CHD was 2.20 (95% confidence
      interval (CI) 1.70-2.85) after adjustment for age and town only, but this fell to
      1.48 (1.09-2.01) after further adjustment. Analysis of t-PA as a continuous
      variable gave similar results. Similarly, when published information on all seven
      available prospective cohort studies in general populations (2119 cases and 8832
      controls in total) was synthesized, the combined odds ratio was 2.18 (1.77-2.69)
      after adjustment for age and sex only, and this fell to 1.47 (1.19-1.81) after
      further adjustment. CONCLUSION: Although there is a statistically significant
      association between circulating concentrations of t-PA antigen and subsequent
      CHD, additional studies are needed to determine to what extent this is
      independent from more established risk factors.

PMID- 14972428
TI  - Prevalence of obstructive sleep apnoea and periodic limb movement in 45 subjects
      with heart transplantation.
AB  - BACKGROUND: Obesity, a major risk factor for obstructive sleep apnoea, is common
      after cardiac transplantation. Case reports have shown development of obstructive
      sleep apnoea in cardiac transplantation recipients. The present study represents
      the first systematic evaluation of sleep disorders after cardiac transplantation.
      OBJECTIVE: To determine the prevalence and clinical impact of sleep disorders in
      a cohort of cardiac transplant recipients. METHODS: This was a cross-sectional
      study at the Veterans Affairs Medical Center. Forty-five of 60 eligible subjects
      agreed to take part in the study. Polysomnography, sleep and health survey
      questionnaires, and laboratory tests were recorded. RESULTS: Thirty-six percent
      had obstructive sleep apnoea-hypopnoea with an index of 15 or more per hour. The
      average apnoea-hypopnoea index was about 50+/-27 (SD) per hour. Sleep apnoea
      resulted in arterial oxyhaemoglobin desaturation, excessive arousals,
      unrefreshing sleep, excessive daytime sleepiness, poor health-related quality of
      life, and hypertension (all P values <0.05). Weight gain since transplantation
      was significantly greater in recipients with obstructive sleep apnoea than those
      without. Thirty-three percent of patients had periodic limb movement with an
      index of >?15/hour and an average of 55+/-43/hour. Forty-five percent of these
      patients had restless legs syndrome. CONCLUSION: Thirty-six percent of cardiac
      transplant recipients have moderate to severe obstructive sleep apnoea. Sleep
      apnoea results in disrupted sleep, desaturation and impaired quality of life.
      Polysomnography should be routinely considered in the ongoing management of most
      cardiac transplant recipients. Treatment of obstructive sleep apnoea may improve
      quality of life and other outcomes of cardiac transplantation.

PMID- 14972429
TI  - Guidelines on prevention, diagnosis and treatment of infective endocarditis
      executive summary; the task force on infective endocarditis of the European
      society of cardiology.

PMID- 14972430
TI  - "Bisoprolol dose-response relationship in patients with congestive heart failure:
      a subgroup analysis in the cardiac insufficiency bisoprolol study(CIBIS II)," by
      Simon T.

PMID- 14972431
TI  - Functional implications of polymorphisms of endothelial nitric oxide synthase
      gene.

PMID- 14972433
TI  - Hormones and the heart - is sleep apnoea the link?

PMID- 14972435
TI  - Use of X-ray absorption imaging to examine heterogeneous diffusion in fractured
      crystalline rocks.
AB  - Heterogeneous diffusion in different regions of a fractured granodiorite from
      Japan has been observed and measured through the use of X-ray absorption imaging.
      These regions include gouge-filled fractures, recrystallized fracture-filling
      material and hydrothermally altered matrix. With the X-ray absorption imaging
      technique, porosity, relative concentration, and relative mass of an iodine
      tracer were imaged in two dimensions with a sub-millimeter pixel size. Because
      portions of the samples analyzed have relatively low porosity values, imaging
      errors can potentially impact the results. For this reason, efforts were made to
      better understand and quantify this error. Based on the X-ray data, pore
      diffusion coefficients (Dp) for the different regions were estimated assuming a
      single diffusion rate and a lognormal multirate distribution of Dp. Results show
      Dp for the gouge-filled fractures are over an order of magnitude greater than
      those of the recrystallized fracture-filling material, which in turn is
      approximately two times greater than those for the altered matrix. The
      recrystallized fracture-filling material was found to exhibit the greatest degree
      of variability. The results of these experiments also provide evidence that
      diffusion from advective zones in fractures through the gouge-filled fractures
      and recrystallized fracture-filling material could increase the pore space
      available for matrix diffusion. This evidence is important for understanding the
      performance of potential nuclear waste repositories in crystalline rocks as
      diffusion is thought to be an important retardation mechanism for radionuclides.

PMID- 14972436
TI  - Reactive solute transport in macroscopically homogeneous porous media: analytical
      solutions for the temporal moments.
AB  - In this work, we investigate one-dimensional solute transport affected by rate
      limited sorption, first-order mass transfer, and first-order transformation.
      Analytical expressions are obtained for the temporal moments of the solute in the
      solution phase. The effect of various rate coefficients on the temporal moments
      is examined. It was found that, in the presence of transformation reactions, the
      mean arrival time, and the spread and skewness of the breakthrough curves, are
      not monotonic functions of the rate coefficients. These solutions will be useful
      as a preliminary analysis tool for ascertaining the relative importance of
      various processes under given conditions. They may also be used to analyze the
      accuracy of various numerical techniques used for simulation of reactive
      transport.

PMID- 14972437
TI  - Geochemical characterization of acid mine drainage from a waste rock pile, Mine
      Doyon, Quebec, Canada.
AB  - Water quality in the unsaturated and saturated zones of a waste rock pile
      containing sulphides was investigated. The main objectives of the project were
      (1) the evaluation of geochemical trends including the acid mine drainage (AMD)
      buffering mechanism and the role of secondary minerals, and (2) the investigation
      of the use of stable isotopes for the interpretation of physical and geochemical
      processes in waste rock. Pore water in unsaturated zone was sampled from suction
      lysimeters and with piezometers in underlying saturated rocks. The investigation
      revealed strong temporal (dry period vs. recharge period), and spatial (slope vs.
      central region of pile) variability in the formation of acid mine drainage. The
      main secondary minerals observed were gypsum and jarosite. There was a higher
      concentration of gypsum in solid phase at Site TBT than at Site 6, suggesting
      that part of the gypsum formed at Site 6 in the early stage of AMD has been
      already dissolved. Formation of secondary minerals contributed to the formation
      of AMD by opening of foliation planes in waste rock, thus increasing the access
      of oxidants like O2 and Fe3+ to previously encapsulated pyrite. The behavior of
      several dissolved species such as Mg, Al, and Fe2+ can be considered as
      conservative in the leachate. Stable isotopes, deuterium and 18O, indicated
      internal evaporation within the pile, and were used to trace recharge pulses from
      snowmelt. Isotope trends for 34S and 18O(SO4) indicated a lack of sulfate
      reduction and zones of active oxidation of pyrite, respectively. Results of
      numerical modeling of pyrite oxidation and gas and water transport were
      consistent with geochemical and isotopic trends and confirmed zones of high
      evaporation rate within the rock pile close to the slope. The results indicate
      that physical and chemical processes within the pile are strongly coupled and
      cannot be considered separately when oxidation rates are high and influence gas
      transport as a result of heat generation.

PMID- 14972438
TI  - Effects of ethanol addition on micellar solubilization and plume migration during
      surfactant enhanced recovery of tetrachloroethene.
AB  - Alcohol addition has been suggested for use in combination with surfactant
      flushing to enhance solubilization kinetics and permit density control of dense
      non-aqueous phase liquid (DNAPL)-laden surfactant plumes. This study examined the
      effects of adding ethanol (EtOH) to a 4% Tween 80 (polyoxyethylene (20) sorbitan
      monooleate) solution used to flush tetrachloroethene (PCE)-contaminated porous
      media. The influence of EtOH concentration, subsurface layering and scale on
      flushing solution delivery and PCE recovery was investigated through a
      combination of experimental and mathematical modeling studies. Results of batch
      experiments demonstrated that the addition of 2.5%, 5% and 10% (wt.) EtOH
      incrementally increased the PCE solubilization capacity and viscosity of the
      surfactant solution, while reducing solution density from 1.002 to 0.986 g/cm3.
      Effluent concentration data obtained from one-dimensional (1-D) column
      experiments were used to characterize rate-limited micellar solubilization of
      residual PCE, which was strongly dependent upon flow velocity and weakly
      dependent upon EtOH concentration. Two-dimensional (2-D) box studies illustrated
      that minor differences (0.008 g/cm3) between flushing and resident solution
      density can strongly influence surfactant front propagation. A two-dimensional
      multiphase simulator, MISER, was used to model the influence of EtOH composition
      on the aqueous flow field and PCE mass recovery. The ability of the numerical
      simulator to predict effluent concentrations and front propagation was
      demonstrated for both 1-D columns and 2-D boxes flushed with EtOH-amended Tween
      80 solutions. Results of this study quantify the potential influence of alcohol
      addition on surfactant solution properties and solubilization capacity, and
      demonstrate the importance of considering small density variations in remedial
      design.

PMID- 14972439
TI  - Hydrochemical stratification in flooded underground mines: an overlooked pitfall.
AB  - The fact that flooded underground mines are commonly hydrochemically stratified
      is often not appreciated. Water samples taken from the water surface in partly
      flooded shafts are often wrongly assumed to represent the water quality existing
      throughout the entire water column. In some cases, treatment systems have been
      designed on the basis of these often misleading water surface samples.
      Stratification can build up within a slowly recovering system where there are few
      lateral inflows and outflows to the system. Less mineralised, shallow-sourced
      water enters at the top of the water column and more heavily mineralised water
      tends to remain at the base of the water column. This water has a high dissolved
      solids content due to dissolution of increasing amounts of pyrite oxidation salts
      and other minerals as the water level rises through the old workings. However,
      such stratification can easily be lost following hydraulic disturbance of the
      system (either by pumping or by natural decant when the water level reaches an
      outflow pathway from the mine system, such as an old adit or shaft collar) and
      often results in surface discharges of poor water quality. Test pumping of one
      such stratified system (Frances Colliery, Scotland) has provided useful
      information about how stratified systems develop, and how they can behave when
      disturbed. The water quality observed after stratification was disturbed by
      pumping was worse than would have been anticipated on the basis of water samples
      taken from the surface of the water column prior to pumping (with concentrations
      of contaminants such as iron and zinc being around two orders of magnitude
      greater than in water surface samples). Taken together with other information
      from the literature, the experience at Frances Colliery supports the proposal of
      criteria for recognising when stratification of mine water quality might be
      anticipated, thus facilitating the timely deployment of measures required for its
      detection at an early stage.

PMID- 14972440
TI  - Groundwater chemistry of the Okelobondo uraninite deposit area (Oklo, Gabon): two
      dimensional reactive transport modelling.
AB  - The stability of uranium-bearing minerals in natural environments is of interest
      to evaluate the feasibility of radioactive waste repositories. The uraninite
      bodies, UO2(s), in the Oklo district (Gabon) are the result of a natural fission
      process, which took place 1970 Ma ago. These deposits can be regarded as natural
      analogues for spent fuel. One of the uraninite bodies, the Okelobondo deposit, is
      located at a depth of 300 m. Groundwater samples from boreholes located at
      shallow depths (100-200 m) show neutral to basic pH, anoxic conditions (Eh = 0.10
      to -0.05 V) and are saturated with respect to uraninite. In contrast, deeper
      samples collected in the vicinity of the ore body are oxidising (Eh = 0.32-0.47
      V), slightly basic (pH = 7.0-8.5) and undersaturated with respect to uraninite.
      These oxidising conditions at depth, if present under repository conditions, may
      affect the stability of uranium oxide. In order to improve our understanding of
      the observed site geochemistry, the available information on the lithology and
      groundwater flow was integrated in a reactive transport model. The chemical
      composition and the pH-Eh values of the water sampled above and in the western
      side of the Okelobondo deposit can be explained by the interaction of meteoric
      recharge with pelites, dolomites and sandstones. The dissolution of Fe(II)
      silicates and the oxidation of the Fe(II)-aqueous species maintained the pH-Eh
      distribution along the Fe(2+)-Fe(OH)3(am) equilibrium, with the result that
      uraninite does not dissolve. This may explain the lower uranium content in the
      water samples from pelites and dolomites above the Okelobondo deposit. The high
      Mn/Fe ratio and the high pH-Eh values of the water sampled at depth, close to the
      Okelobondo deposit, suggest a control by the Mn(2+)-MnOOH(s) equilibrium. This
      control is attributed to the dissolution of a large rhodochrosite, MnCO3(s), and
      manganite, MnOOH(s) deposit in the recharge area on the eastern side.

PMID- 14972441
TI  - An inverse system for incorporation of conditioning to pressure and streamline
      based calibration.
AB  - A streamline-based history matching technique is employed to perform fast and
      efficient permeability identification and to integrate tracer data into an
      inverse model. To incorporate tracer data into the inverse model, a given tracer
      breakthrough curve is interpreted as cumulative breakthrough along independent
      streamlines. Permeabilities are modified along each streamline to match the
      tracer breakthrough curve. In this way, there is no explicit computation of
      sensitivity coefficients, nor any matrix inversion. However, this approach is
      incomplete by itself. Since the modifications occur along the streamlines, the
      identified permeability distribution is often incompatible with the actual
      permeability distribution. Thus, streamlines should be positioned correctly
      before the streamline-based method is applied. To accomplish this, geostatistical
      methods such as kriging and sequential Gaussian simulation (SGS) are implemented
      to provide an appropriate disposition of streamlines at the beginning of the
      inverse process. Then, permeabilities are iteratively calibrated in a
      conventional grid system to satisfy pressure and permeability observation data,
      and simultaneously modified along streamlines to match tracer data. The two
      independent optimization processes assist mutually and lead to stable convergence
      to a minimum. By applying the proposed inverse system to synthetic reference
      fields, it is observed that identified fields satisfactorily reproduce the
      permeability distribution of the reference fields. In addition, the pressure
      distributions of the identified and the reference fields are fairly alike, and
      the identified tracer breakthrough curves are well fitted to those of the
      reference fields. With regard to spatial patterns of transport behaviors, the
      streamlines of the identified fields show similar trajectories to those of the
      reference fields, and the time of flight distributions of the inversed fields are
      also analogous to those of the reference fields. The proposed inverse system is
      capable of estimating the future performance of a two-dimensional aquifer from a
      constrained number of permeability and pressure observation data accompanied by
      tracer data.

PMID- 14972443
TI  - Aspects of human fetoplacental vasculogenesis and angiogenesis. I. Molecular
      regulation.
AB  - Patterns of fetoplacental angiogenesis vary during gestation and in association
      with certain pregnancy pathologies. In a set of three linked reviews, we provide
      a survey of current knowledge about the molecular regulation, cellular players,
      qualitative and quantitative morphological features of the vascularization of
      human placental villi. Here, an account is given of the role played by hypoxia
      inducible factor in mediating the effects of oxygen on production of growth
      factor ligands and receptors which regulate angiogenesis and vessel maturation.
      However, it should be noted that, for the human placenta early in gestation, the
      normal (i.e. physiological) partial pressure of O(2)is low but this does not mean
      that the tissue is hypoxic. Thus, the mechanisms of regulating angiogenic growth
      factor production may differ at this time in comparison to those found later in
      gestation or in other tissues or organs. The vasculature in the placenta is
      plastic and changes markedly as gestation progresses. This is controlled by the
      complex interplay between physical factors and chemical factors including oxygen,
      growth factors and growth inhibitors. The companion reviews describe
      morphological features of normal and pathological development of the human
      placenta in the context of the factors discussed here.

PMID- 14972444
TI  - Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes
      during normal pregnancy.
AB  - In this second review, we describe the main morphological events which accompany
      the development of the fetoplacental vascular system throughout normal human
      pregnancy and summarize findings on the expression of angiogenic growth factors
      and their receptors. Fetoplacental vasculogenesis starts at day 21 after
      conception by formation of haemangioblastic cords. In the following phase of
      branching angiogenesis (day 32 to week 25 post conception), haemangioblastic
      cords develop into a richly branched villous capillary bed with low fetoplacental
      blood flow impedance. This period is characterized by high placental levels of
      VEGF but moderate PlGF expression. In week 15, large centrally located villi show
      regression of peripheral capillary nets. In parallel, some remaining central
      capillaries acquire a tunica media and transform into arteries and veins.
      Beginning at about week 25 in the newly formed peripheral villi, angiogenesis
      switches from branching to non-branching and this period is accompanied by a
      steep drop in VEGF and a slower decline in PlGF expression. As a consequence of
      this switch, long poorly branched capillary loops are formed in the periphery of
      the fetoplacental vascular trees. These increase fetoplacental impedance but
      blood flow still increases due to rising fetal blood pressure. The possible
      interactions between (a). the biphasic development of intraplacental oxygen
      tensions, (b). changes in VEGF and PlGF levels and (c). developing vascular
      geometry are discussed. Special attention is given to the obvious discrepancy
      between sudden elevation of intervillous oxygen tensions which is not coincident
      with the appearance of angiogenic growth factor peaks and the switch from
      branching to non-branching angiogenesis. Finally, we deal with methods of
      quantifying aspects of angiogenesis in the villous vascular system and summarize
      the main findings during uncomplicated human pregnancy.

PMID- 14972445
TI  - Aspects of human fetoplacental vasculogenesis and angiogenesis. III. Changes in
      complicated pregnancies.
AB  - Patterns of fetoplacental angiogenesis vary not only during the course of a
      normal pregnancy but also in certain pregnancy pathologies. Here, we review some
      of the molecular and morphological events which occur in complicated pregnancies.
      The pregnancy complications are chosen in an attempt to represent the possible
      different origins (preplacental, uteroplacental, postplacental) of fetal hypoxia.
      Molecular events focus on reported changes in hypoxia-inducible factors,
      angiopoietins and the vascular endothelial, basic fibroblast and placenta growth
      factors and their receptors. Morphological changes focus on patterns of
      angiogenesis (branching and non-branching) and a consistent set of morphometric
      descriptors (covering measures of total capillary growth, villous capillarization
      and capillary size and shape in transverse section). Apart from some
      uncertainties due to lack of information, or failure to resolve fully the effects
      of intrauterine growth restriction and pre-eclampsia, alterations in the
      angiogenic growth factors and morphologies of capillaries and villi in different
      complicated pregnancies seem to conform reasonably well to those predicted by the
      fetal hypoxia paradigm. However, it is clear that future studies on the effects
      of different origins of fetal hypoxia should exercise more care in the choice and
      interpretation of relevant descriptors and take more account of the parallel
      effects of possible confounders. In addition, rather than comparing uncomplicated
      and complicated pregnancies only at term, more information about molecular and
      morphological events that occur throughout gestation would be extremely valuable.
      This includes further studies on changes in growth factor receptors, the less
      well-documented angiogenic factors (e.g. angiogenin, angiostatin, endostatin) and
      the associations between endothelial cells and pericytes. A more integrated
      approach involving also parallel analysis of the effects of erythropoietin and
      other potential vasoactive factors on the behaviour and morphology of fetal
      vessels would be beneficial.

PMID- 14972446
TI  - CD83(+)dendritic cells in the decidua of women with recurrent miscarriage and
      normal pregnancy.
AB  - Immunological factors have been postulated to play a role in the aetiology of
      recurrent miscarriage as the fetus and placenta are semi-allogenic to the mother.
      Potent immunostimulatory (CD83(+)) dendritic cells have recently been identified
      in the uterine decidua. This study was conducted to examine whether decidual
      dendritic cells could play a role in the aetiology of recurrent miscarriage.
      First trimester placental and decidual biopsies were obtained from 40 women with
      recurrent miscarriage and 15 gestation-matched normal controls. These biopsies
      were screened by immunohistochemistry for CD83(+)cells. Staining was analysed by
      light microscopy and digital image analysis. In both recurrent miscarriage and
      normal pregnancy, CD83(+)dendritic cells were localized to the decidua.
      Individual dendritic cells were present in the decidual stroma or in clusters of
      3-4 dendritic cells, in lymphoid aggregates. There were no significant
      differences in decidual CD83(+)dendritic cell density between women with
      recurrent miscarriage and normal pregnancy when the groups were compared as a
      whole. However, when segregated by gestational age, decidua from women with
      recurrent miscarriage at 8 weeks' gestation contained significantly more
      dendritic cells than gestational age-matched normal controls. This suggests
      dendritic cells may play a role in the aetiology of some cases of recurrent
      miscarriage.

PMID- 14972447
TI  - Cytokeratin immunohistochemistry: a procedure for exclusion of pregnancy in
      chorionic villi-negative specimen.
AB  - The confirmation or exclusion of the presence of products of conception (POC) in
      biological material may be crucial. This analysis has been undertaken to check
      how efficient the H&E examination of the putative POC specimen is in practice and
      to prove the hypothesis that the use of cytokeratin immunostaining can increase
      the diagnostic accuracy. Of 1078 POC specimens, 94 cases which were signed out as
      'No chorionic villi identified' or 'Negative for POC' and in which all submitted
      material was histologically examined, were re-reviewed histologically and
      examined immunohistologically using the low molecular weight cytokeratin antibody
      CAM5.2. In six cases, the originally missed trophoblastic cells were found on re
      review of the H&E slides, which was confirmed by CAM5.2 immunostaining. Of seven
      further cases which were suspicious for trophoblastic cells on re-review, three
      cases were positive for trophoblastic cells by CAM5.2 and four were negative. Of
      the remaining 81 cases negative for trophoblastic cells on H&E re-review, CAM5.2
      was positive for the trophoblast in 13 (16 per cent). There were no false
      positive cases on CAM5.2 immunostaining of the endometrial curettings in 22
      ectopic pregnancies and 22 cases with dysfunctional endometrial bleeding
      clinically and secretory endometrium histologically. Therefore, although the
      overall efficiency of the original diagnosis could have been as high as 98 per
      cent (1029 of 1051), the false negative rate was 23 per cent (22 of 94) in the
      chorionic villi-negative material. Even though the morphology of trophoblastic
      cells on conventional H&E staining is well known, it may be practically difficult
      to exclude pregnancy by the examination of uterine contents using conventional
      H&E staining only. The use of the cytokeratin immunostaining can decrease the
      rate significantly and should be considered in all chorionic villi-negative
      specimens without obvious extravillous trophoblasts.

PMID- 14972448
TI  - A primary cell culture system for human cytotrophoblasts of proximal
      cytotrophoblast cell columns enabling in vitro acquisition of the extra-villous
      phenotype.
AB  - Cytotrophoblast (CT) differentiation into the extra-villous phenotype is a
      crucial process in initiating their invasion into the decidua and thereby
      developing the placenta. However, how CTs differentiate into extra-villous CTs
      (EVCTs) is not fully elucidated. To address this, a suitable culture model for
      CTs has been long-sought. But this has been hampered by annoying problems such
      as; cell aggregation, in vitro syncytialization, low plating efficiency, etc. The
      aim of this study is to develop a culture system in which CTs differentiate into
      EVCTs. CTs were isolated from the first trimester placenta using density gradient
      separation and immuno-depletion using anti-CD9 antibody to remove contaminating
      fibroblasts and EVCTs. The resultant isolated CTs were found to have the
      character similar to poorly differentiated CTs comprising proximal
      cytotrophoblastic cell columns as confirmed by immunocytochemical and
      flowcytometric analyses. When cultured on type 4 collagen-coated plates in
      culture media containing low calcium concentration, CTs neither aggregated nor
      syncytialized, remaining mononuclear and monolayer state. Interestingly, cultured
      CTs gradually upregulated integrin alpha1, CD9, and human leukocyte antigen (HLA)
      G; the known markers specific for EVCTs invading into the decidua diffusely.
      Hence, the CT culture system provides a sophisticated experimental model in which
      highly purified CTs acquire the extra-villous phenotype without syncytialization.

PMID- 14972449
TI  - Analysis of transcriptional control elements in the 5'-upstream region of ovine
      interferon-tau gene using feeder-independent caprine trophoblast cell line, HTS
      1.
AB  - Interferon-tau (IFNtau) is a protein secreted from the embryonic trophectoderm of
      ruminant ungulates during peri-implantation period. This protein acts on the
      uterine endometrium, which indirectly maintains corpus luteum function, and is
      therefore considered essential for the process of maternal recognition of
      pregnancy. Transcriptional regulation of IFNtau genes had been examined using
      human choriocarcinoma cell lines, JEG-3 or JAR, however, molecular mechanisms by
      which cell and term specific IFNtau expression are regulated have not been
      elucidated. Recently, a feeder cell free-trophoblast cell line derived from Shiba
      goat placenta, termed HTS-1, was established. In the present investigation, the
      5'-upstream region of ovine IFNtau (oIFNtau) gene was analysed using this cell
      line, which would provide a more suitable system for studies of the ovine
      trophoblast specific gene than human choriocarcinoma cells. Variously modified 5'
      upstream sequences of the oIFNtau gene fused to a luciferase reporter gene were
      transiently transfected into HTS-1 cells, and human JEG-3 cells were used as a
      control. These results and co-transfection with expression vectors revealed that
      Ets-2 binding site in the promoter region was important in HTS-1, whereas AP-1
      that binds to the enhancer region was a major activator in JEG-3. By
      electrophoretic mobility shift assay, a nuclear protein from HTS-1 cells was
      confirmed to bind specifically to the Ets-2 site of oIFNtau promoter region.
      Differences in amounts of AP-1 and Ets-2 protein were demonstrated in nuclear
      extracts from HTS-1, JEG-3 and ovine conceptuses. Substantial differences on
      oIFNtau gene transcriptions found between caprine HTS-1 and human JEG-3 cells
      suggest that this cell line could be valuable in the elucidation of a molecular
      mechanism(s) by which oIFNtau gene expression is regulated in a cell specific
      manner.

PMID- 14972450
TI  - Signal pathway involved in increased expression of neutral endopeptidase 24.11 by
      gonadotropin releasing hormone in choriocarcinoma cells.
AB  - Neutral endopeptidase 24.11 (NEP) is known to regulate cellular functions by
      degrading several bioactive peptides, such as gonadotropin-releasing hormone
      (GnRH). The present study was performed to clarify the mechanisms of NEP
      expression by GnRH in human choriocarcinoma (BeWo) cells. GnRH increased NEP
      expression and enzyme activity in a dose- and time-dependent manner in BeWo
      cells. The phosphorylation levels of protein kinase C (PKC) delta, p38 mitogen
      activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK1 and 2) were
      enhanced after 10 min exposure of 10(-6)m GnRH. The effect of GnRH on both NEP
      expression and enzyme activity was completely inhibited by inhibitors of PKC, PKC
      delta, and p38MAPK. Cell number was reduced by 54.4 per cent of the control by
      culture with 10(-6)m GnRH for 24 h. However, phosphoramidon, a NEP specific
      inhibitor, inhibited antiproliferative effect of GnRH and reverted to the control
      level. In conclusion, GnRH induces NEP expression by PKC delta and p38MAPK, and
      increased NEP expression may be involved in antiproliferative effect in BeWo
      cells.

PMID- 14972451
TI  - VEGF, bFGF and their receptors at the fetal-maternal interface of the rhesus
      monkey.
AB  - Placental development involves trophoblast outgrowth and a coordinated
      angiogenesis in the implantation site. In this study, expression of angiogenic
      factors, vascular endothelial growth factor (VEGF), basic fibroblast growth
      factor (bFGF), VEGF receptors, kinase insert domain-containing region (KDR), and
      bFGF receptor Flg was characterized at the maternal-embryonic boundary of the
      rhesus monkey on Day 17, 19, 28 and 34 of pregnancy. Immunohistochemistry and in
      situ hybridization showed that VEGF mRNA and protein were both strongly expressed
      in the cytotrophoblast, the blood vessels and certain immunocytes. These sites
      were also immunopositive for KDR. In addition to the vascular endothelial cells
      and the vascular smooth muscle cells, the protein and mRNA for bFGF were also
      detected in cyto/syncytiotrophoblast bilayer, whereas the staining for Flg
      protein was mainly localized in the cytotrophoblast cells. The staining degree of
      VEGF and bFGF in the villi gradually decreased with the development of placenta.
      Strong expression of bFGF, Flg and KDR was also detected in the decidual cells.
      These data suggest that VEGF and bFGF may be involved in angiogenesis,
      cytotrophoblast proliferation and migration during early stage of placentation in
      the rhesus monkey.

PMID- 14972452
TI  - Immunohistological localization of insulin-like growth factor binding protein-1
      in primary implantation sites and trauma-induced deciduomal tissues of the rhesus
      monkey.
AB  - We have earlier demonstrated that there is a close similarity in the temporo
      spatial pattern in the onset of oedema, epithelial-plaque transformation, stromal
      decidualization and influx of granulated lymphocytes in artificially trauma
      induced deciduomal endometrium with such events in maternal endometrium at the
      primary implantation site during early stages of pregnancy in the rhesus monkey.
      In the present study, we have immunohistochemically examined whether the pattern
      of insulin-like growth factor-binding protein 1 (IGFBP-1) protein expression in
      conceptus tissue and maternal endometrium during lacunae and villous placenta
      stages of gestation in the rhesus monkey is developmental stage-specific and
      whether a discernible difference exists in the temporo-spatial characteristics of
      IGFBP-1 protein expression between conceptus associated implantation
      decidualization and trauma induced deciduoma in the rhesus monkey. Trophoblast
      cells failed to exhibit IGFBP-1 immunopositive staining at any stage of
      implantation-placentation studied. Epithelial cells in plaque acini, endothelial
      cells, and vascular smooth muscle also did not show any immunopositive staining
      for IGFBP-1 in samples of primary implantation sites and trauma-induced
      deciduoma. Maternal endometrial epithelial and stromal-decidual cells however
      exhibited a temporal and spatial pattern of IGFBP-1 expression in cell-type
      specific manner and clear distinctions were observed between conception and
      deciduoma samples. Our results suggest that IGFBP-1 expression is highly tissue
      and development-specific and that conceptus-derived signals are necessary to
      initiate the glandular expression of IGFBP-1 during the early stage of gestation.

PMID- 14972454
TI  - Structure of the definitive placenta of the tenrec, Echinops telfairi.
AB  - Until recently, tenrecs were classified with insectivores in the order
      Lipotyphla, but nucleotide sequence data suggest they have closer affinities with
      a group of African mammals called Afrotheria. The placenta of Echinops has not
      been described and no studies involving electron microscopy of the placenta of
      any species of tenrec have been published. We used light and transmission
      electron microscopy to examine fixed placentae of embryos ranging from 25-66 mm
      in length. The placental disk is situated in the antimesometrial portion of the
      bicornuate uterus. The greater part of the disk consists of a labyrinth underlain
      by a spongy zone. The interhaemal barrier is unusual in that the trophoblastic
      component is a single layer of cytotrophoblast. These trophoblast cells have
      thick areas especially near the nuclei and extensive thin flanges but only
      occasionally have membrane-closed pore regions. The luminal surface has isolated
      patches of microvilli, and pinocytotic vesicles are numerous both apically and
      basally. In the centre of the placental disk is an elaborately folded
      haemophagous region. The primary folds have allantoic endoderm at one surface and
      columnar cytotrophoblast at the other. These trophoblast cells have numerous
      lipid droplets and vesicles, and often contain large yellow pigment crystalloids.
      The labyrinthine zone ends abruptly at the margins of the placental disk.
      However, the endoderm and connective tissue of the allantois and a layer of
      cytotrophoblast extend beyond the placental disk as a paraplacental region. Some
      of these distinctive features of Echinops placenta are shared with individual
      afrotherians, but no significant characteristic of definitive placentation is
      shared by all the Afrotheria.

PMID- 14972453
TI  - Umbilical vein and placental vessels from newborns with hereditary haemorrhagic
      telangiectasia type 1 genotype are normal despite reduced expression of endoglin.
AB  - Hereditary haemorrhagic telangiectasia, HHT, is an autosomal dominant disorder
      that affects approximately 1 in 8000 people. HHT1 is associated with mutations in
      the ENG (Endoglin) gene and with haploinsufficiency. The disorder is
      characterized by focally dilated vessels, which can lead to arteriovenous
      malformations and serious complications even in young children. In the current
      study, umbilical cord and placenta samples from newborns with ENG mutations were
      analyzed to estimate the level of corresponding protein and look for potential
      vascular dysplasia. We confirmed, using metabolic labelling and flow cytometry,
      that endoglin levels were significantly reduced to median values of 47 per cent
      (range 32-56 per cent) and 58 per cent (46-90 per cent), respectively, in human
      umbilical vein endothelial cells derived from newborns with ENG mutations (HHT1
      group; n=18) relative to samples from newborns shown not to have the familial
      mutation (non-HHT group). We also quantified the relative expression of endoglin
      by estimating the endoglin/PECAM-1 staining ratio in tissue sections. We observed
      significantly lower values in the HHT1 group, compared to the non-HHT group for
      the umbilical vein (n=9; median 0.6 vs 0.9; ranges 0.2-1.0 and 0.5-1.5) and for
      placental stem villus vessels (n=9 and 10; median 0.42 vs 0.93; ranges 0.24-0.58
      and 0.56-1.18). No differences in the estimated umbilical vein cross-sectional
      area and in the proportion of vessels present in placental villi were observed in
      sections from the HHT1 group relative to the non-HHT group. Thus, blood vessels
      from HHT1 individuals are maintained intact in the umbilical vein and placenta
      during pregnancy and delivery, despite a significant reduction in endoglin
      expression.

PMID- 14972455
TI  - Thomas Huxley and the rat placenta in the early debates on evolution.
AB  - The 19th century debates on mammalian classification in the light of the new
      evolutionary thinking led to controversies between Thomas Huxley and Richard Owen
      concerning the value of the placenta as a representative key organ. As a main
      point in his argument, Huxley provided a detailed description of a sectioned rat
      placenta, highlighting the importance of decidualization of the uterus as an
      argument supporting an evolutionary relationship between rodents, insectivores
      and primates, an idea hotly contested by Owen. In addition, he illustrated and
      correctly interpreted the maternal blood supply from uterus to placenta in
      striking detail. During the succeeding decades the key role of trophoblast in
      placenta formation was discovered, and the decidua became neglected in later
      comparative studies. Nevertheless, at the present time trophoblast-decidual
      interaction is regarded as an extremely important feature of placental
      development in both primates and rodents, and Huxley can therefore rightfully be
      considered as an early pioneer in placental research.

PMID- 14972456
TI  - Occlusion of arterio-arterial anastomosis manifesting as acute twin-twin
      transfusion syndrome.
AB  - In vivo, ex vivo and modelling studies suggest that arterio-arterial anastomoses
      (AAAs) protect against haemodynamic imbalance in monochorionic twins and thus the
      development of TTTS. We report the acute onset of severe TTTS at 34 weeks'
      gestation in a patient with an antenatally visualized AAA which was shown at
      injection studies to have been obliterated, presumably by thrombosis. Computer
      modelling with the relevant clinical data confirmed that occlusion of the AAA
      alone was sufficient to reproduce the clinical manifestations. A study of the
      vascular configuration of AAA in the fixed placenta suggested that its small
      diameter and turbulent flow may have contributed to its occlusion. This case
      report shows that the unmasking of unbalanced AVA configurations by occlusion of
      a protective AAA can manifest as TTTS.

PMID- 14972457
TI  - Assisted reproductive technology in the new millennium: part II.

PMID- 14972458
TI  - Diagnosis of noncalcareous hydronephrosis: role of magnetic resonance urography
      and noncontrast computed tomography.
AB  - OBJECTIVES: To evaluate the role of magnetic resonance urography (MRU) and
      noncontrast computed tomography (NCCT) in the diagnosis of noncalcareous
      hydronephrosis when excretory urography (intravenous urography) is either
      contraindicated or inconclusive. METHODS: A total 108 consecutive patients with
      noncalcareous hydronephrosis were included in this study. In all patients,
      intravenous urography was either contraindicated or could not determine the
      diagnosis. In all patients, calculus obstruction was excluded by NCCT and all
      underwent heavily T2-weighted MRU. The final definitive diagnosis was established
      by retrograde or antegrade ureterography, endoscopy, or open surgery and was
      considered the reference standard for the diagnosis of obstruction. Normal
      kidneys in patients with unilateral obstruction were considered the reference
      standard for the absence of obstruction. The results of MRU were compared with
      those of NCCT regarding sensitivity, specificity, and overall accuracy. RESULTS:
      Of the 108 patients, 5 had bilateral obstruction and the remaining 103 had
      unilateral obstruction. Of the latter group, 5 had a solitary kidney; therefore,
      the total number of renal units was 211 (113 obstructed and 98 normal units).
      Ureteral strictures were identified by NCCT in 15 (28%) of 54 and by MRU in 45
      (83%) of 54 patients. Bladder, ureter, or prostate tumors causing ureteral
      obstruction could be diagnosed in one half of the 54 patients with such tumors by
      NCCT (27 of 54) and in all but 2 patients by MRU (52 of 54). Both NCCT and MRU
      could identify all extraurinary causes of obstruction. Overall, of the 113
      kidneys with noncalculus obstruction, the cause could be identified by MRU in 102
      (sensitivity of 90%) and by NCCT in 47 (sensitivity of 42%), a difference of
      statistically significant value in favor of MRU (P <0.001). The specificity of T2
      weighted MRU and NCCT was 100% and 99%, respectively (not a statistically
      significant difference). The overall accuracy of T2-weighted MRU and NCCT was 95%
      and 68%, respectively (P <0.001). CONCLUSIONS: In patients with ureteral
      obstruction in whom intravenous urography is not helpful and after NCCT has
      excluded stone disease, heavily T2-weighted MRU is a sensitive and specific
      method in the identification of the cause of obstruction.

PMID- 14972459
TI  - Percutaneous antegrade endopyelotomy: long-term results from one institution.
AB  - OBJECTIVES: To assess the long-term efficacy of percutaneous antegrade
      endopyelotomy for the treatment of ureteropelvic junction (UPJ) obstruction
      performed at a single institution during a 10-year period. We provide alterations
      in investigation and management strategies on the basis of the results. METHODS:
      From July 1990 to June 2001, 80 patients with clinical and radiographic evidence
      of UPJ obstruction underwent percutaneous endopyelotomy for the treatment of
      primary (n = 61) or secondary (n = 19) UPJ obstruction. The mean patient age was
      35 years (range 4 to 76). Percutaneous endopyelotomy was performed in a standard
      fashion using either a hooked-knife (n = 77) or holmium laser (n = 3). RESULTS:
      With a mean patient follow-up of 55 months (range 16 to 138), the overall success
      rate was 67% (53 of 79). The success rate for primary and secondary UPJ
      obstruction was 65% (39 of 60) and 74% (14 of 19), respectively. The mean time to
      failure was 15 months (range 1 to 79). Operative intervention for 24 of 26
      patients with failure included open pyeloplasty (n = 18, 75%), indwelling
      ureteral stenting (n = 2, 8%), retrograde balloon dilation (n = 1, 4%), and
      nephrectomy (n = 3, 13%). Two asymptomatic patients with recurrent radiographic
      evidence of obstruction elected conservative follow-up. Significant crossing
      vessels were encountered at open pyeloplasty in 15 (83%) of 18 patients.
      CONCLUSIONS: Our long-term results of percutaneous endopyelotomy demonstrated
      somewhat lower success rates than that reported in published studies. Long-term
      follow-up is critical in identifying late failures. The high prevalence of
      crossing vessels encountered at open pyeloplasty provided further evidence to
      support its role in endopyelotomy failure. Routine preoperative helical computed
      tomography to detect significant crossing vessels is recommended. Patients with
      crossing vessels are likely better served with operative techniques that
      specifically address this issue, namely open or laparoscopic pyeloplasty.

PMID- 14972460
TI  - Tumor-size breakpoint for prognostic stratification of localized renal cell
      carcinoma.
AB  - OBJECTIVES: To identify an optimal tumor-size breakpoint to distinguish between
      two groups with different prognoses in a large cohort of patients with localized
      renal cell carcinoma (RCC). METHODS: We reviewed the clinical records of 813
      patients who had undergone surgical treatment for localized RCC from 1976 to
      2000. The optimal breakpoint for the pathologic size was calculated by receiver
      operating characteristic curve analysis. RESULTS: The receiver operating
      characteristic curve analysis identified 5.5 cm as the optimal breakpoint to
      predict cancer-specific survival rates. The pathologic size was 5.5 cm or less in
      565 neoplasms (69.5%) and more than 5.5 cm in 248 (30.5%). In the multivariate
      analysis, the more predictive model included the 5.5-cm-or-less pathologic size
      breakpoint. The pathologic size of 7 cm or less was not an independent variable
      in this cohort of patients. CONCLUSIONS: In a large cohort of patients with
      localized RCC, 5.5 cm was the optimal breakpoint to classify patients with
      localized RCC into two subgroups with different prognoses; the 7-cm-or-less
      cutoff value was not an independent variable. The data obtained by analyzing a
      large cohort of consecutive patients should be validated by other large series
      with the prospective of redefining the TNM staging system.

PMID- 14972462
TI  - Laparoscopic partial nephrectomy with temporary arterial occlusion: description
      of technique and renal functional outcomes.
AB  - OBJECTIVES: To report our laparoscopic partial nephrectomy experience and the
      impact of temporary arterial occlusion during laparoscopic partial nephrectomy on
      postoperative renal function. Laparoscopic partial nephrectomy is increasingly
      popular but remains technically challenging. METHODS: Laparoscopic partial
      nephrectomy was performed in 27 patients, with arterial occlusion in 15 cases.
      Postoperative renal function was evaluated with serum creatinine in all patients
      and postoperative technetium-99m mercaptoacetyl triglycine renal scans in a
      subset of patients after arterial occlusion. RESULTS: The group with arterial
      occlusion (n = 15) did not differ from those without arterial occlusion (n = 12)
      with respect to age, body mass index, American Society of Anesthesiologists
      score, lesion size, operative time, blood loss, or complications. In patients
      undergoing arterial occlusion, the mean warm ischemia time was 43 +/- 10 minutes
      (range 25 to 65). The preoperative and postoperative serum creatinine levels were
      unchanged in patients with (1.07 +/- 0.4 to 1.15 +/- 0.4 ng/dL; P = 0.24) and
      without (0.96 +/- 0.22 to 1.07 +/- 0.27 ng/dL; P = 0.14) arterial occlusion. The
      tumor size on imaging correlated with postoperative serum creatinine (r2 = 0.450,
      P = 0.04). Nuclear renography was performed in 9 patients (60%) after renal
      artery occlusion. The mean differential renal function of the operated kidney
      (49%) was similar to that of the contralateral kidney (51%) and was not
      associated with warm ischemic time or tumor size. CONCLUSIONS: Temporary arterial
      occlusion during laparoscopic partial nephrectomy does not appear to affect short
      term renal function adversely. We believe that this technique can be safely
      performed when significant bleeding or entry into the collecting system is
      anticipated. Additional study is warranted to identify the maximal time of warm
      ischemia and ways to reduce potential renal injury.

PMID- 14972463
TI  - Laparoscopic radical nephrectomy in obese patients: outcomes and technical
      considerations.
AB  - OBJECTIVES: To review our technique and experience with laparoscopic radical
      nephrectomy (LRN) in the obese patient population. Obesity has been considered a
      potential risk factor for poor outcomes in a variety of surgical procedures and
      has been considered a relative contraindication to laparoscopy. Since 1996, with
      increased experience and technical modifications, obesity has not been considered
      a contraindication for laparoscopy at our institution. METHODS: Retrospective
      data were obtained for all patients who underwent LRN from January 1997 to
      December 2000. A body mass index (Quetelet's index) greater than 30 was used to
      define obese patients. Technical modifications included slightly greater
      insufflation pressures and a lateral shift in trocar sites. The obese
      laparoscopic group was compared with the nonobese laparoscopic group. RESULTS: Of
      101 patients who underwent LRN, 69 were not obese and 32 were obese. No
      statistically significant differences were observed in any of the analyzed
      operative data between the nonobese laparoscopic group and obese laparoscopic
      group, including a mean operative time of 220 and 242 minutes, respectively.
      Other factors assessed were the time to ambulation, length of hospital stay,
      conversion rate to an open procedure, and complication rate, which also
      demonstrated no statistically significant difference. Only one conversion to an
      open procedure was required in both the obese and the nonobese laparoscopic
      groups. CONCLUSIONS: With minor technical modifications, LRN can be safely
      performed in obese patients. Proper trocar site selection and greater
      insufflation pressures were critical for success. The differences in the
      intraoperative and postoperative course of LRN in obese and nonobese patients
      were not statistically significant. Obesity should not be considered a
      contraindication to laparoscopic nephrectomy.

PMID- 14972466
TI  - Association of prostate cancer risk with insulin, glucose, and anthropometry in
      the Baltimore longitudinal study of aging.
AB  - OBJECTIVES: To examine the relationship of insulin, glucose, and anthropometry
      with the subsequent risk of prostate cancer. METHODS: The relative risk of
      prostate cancer by insulin, glucose, and anthropometric measures was evaluated in
      823 male participants (87 patients with prostate cancer in 10,737 person-years of
      follow-up) of the Baltimore Longitudinal Study of Aging who had at least one
      fasting plasma insulin measurement, which was prediagnostic for those with
      prostate cancer. Age-adjusted and multivariate-adjusted relative risks were
      estimated from Cox proportional hazards regression models. RESULTS: Insulin
      concentrations were in the normal range (defined as less than 20 microU/mL) for
      95.1% of participants. Fasting insulin and glucose levels were unrelated to
      prostate cancer risk in our overall analysis (P for trend = 0.56 and 0.45,
      respectively). The relative risk of prostate cancer for the second through fourth
      quartiles of the waist/hip ratio compared with the lowest quartile was 2.10,
      1.96, and 2.06, respectively (P for trend = 0.32). Risk was unrelated to waist
      circumference and body mass index. CONCLUSIONS: The results of this study do not
      conclusively support positive associations of markers of insulin and glucose
      metabolism and obesity with prostate cancer. Additional larger prospective
      studies with repeated measure of these parameters are warranted to explore these
      associations further.

PMID- 14972467
TI  - Effects of a genistein-rich extract on PSA levels in men with a history of
      prostate cancer.
AB  - OBJECTIVES: To determine whether supplemental amounts of soy isoflavone
      (genistein-rich extract) would lower prostate-specific antigen (PSA) levels more
      than 50% in patients with prostate cancer (CaP). METHODS: A total of 62 men (mean
      age 73.6 years, range 61.4 to 89.3) with histologically proven CaP who had two
      consecutive elevated PSA readings were accrued during a 13-month period. An open
      label pilot study was conducted for 6 months in which the patients took capsules
      containing the genistein-rich extract three times daily by mouth. The subjects
      were in one of five groups: after radical retropubic prostatectomy (n = 9), after
      radiotherapy (n = 17), after both radical retropubic prostatectomy and
      radiotherapy (n = 6), off-cycle during hormonal therapy (intermittent hormones; n
      = 14), or active surveillance (n = 16). The primary endpoint for the trial was a
      50% reduction in the PSA level at 6 months compared with before treatment.
      RESULTS: Of the 62 men enrolled, 52 were available for evaluation at 6 months.
      Three patients discontinued because of adverse events (diarrhea) and seven
      because of personal choice. One of 52 patients had a more than 50% reduction in
      the PSA level (1.9% response, 95% confidence interval 0.1% to 10.3%). An
      additional 7 patients had PSA reductions that were less than 50%. All 8 patients
      with lower PSA levels at 6 months were in the active surveillance (watchful
      waiting) treatment subgroup. Repeated measure regression models allowing for
      correlation between initial levels and change also indicated a decline in PSA in
      this group compared with other groups: 0 of 52 had a complete response, 9 (17%)
      had a partial response, 8 (15%) had stable disease, and 35 (67%) had disease
      progression. In the 9 patients with a partial response, 6 had pathologic findings
      that were moderately differentiated, 2 had well-differentiated findings, and 1
      had poorly differentiated findings. Therefore, the response in this group of
      patients did not appear to be driven by the Gleason score. The total testosterone
      level was lowered in one of the patients responding, but it was higher in five
      others. CONCLUSIONS: A genistein-rich extract as the sole treatment for CaP did
      not reduce PSA levels by 50% or more in 51 of 52 subjects. Thus, it does not
      appear to be an effective treatment for CaP when given alone. However, 8 of 13
      evaluated patients in the active surveillance group had either no rise or a
      decline in PSA levels of less than 50%. More study is warranted for those
      choosing active surveillance.

PMID- 14972468
TI  - Comparative study of effects of extracorporeal magnetic innervation versus
      electrical stimulation for urinary incontinence after radical prostatectomy.
AB  - OBJECTIVES: To perform a randomized comparative study to investigate the clinical
      effects of extracorporeal magnetic innervation (ExMI) and functional electrical
      stimulation (FES) on urinary incontinence after retropubic radical prostatectomy.
      METHODS: Thirty-six patients with urinary incontinence after radical
      prostatectomy were randomly assigned to three groups (12 patients each in the
      FES, ExMI, and control groups). For FES, an anal electrode was used. Pulses of 20
      Hz square waves at a 300-micros pulse duration were used for 15 minutes twice
      daily for 1 month. For ExMI, the Neocontrol system was used. The treatment
      sessions were for 20 minutes, twice a week for 2 months. The frequency of the
      pulse field was 10 Hz for 10 minutes, followed by a second treatment at 50 Hz for
      10 minutes. For the control group, only pelvic floor muscle exercises were
      performed. Objective measures included bladder diaries, 24-hour pad weight
      testing, and a quality-of-life survey, at 1, 2, and 4 weeks and 2, 3, 4, 5, and 6
      months after removing the catheter. RESULTS: The leakage weight during the 24
      hours after removing the catheter was 684, 698, and 664 g for the FES, ExMI, and
      control groups, respectively. At 1 month, it was 72, 83, and 175 g (FES versus
      control, P <0.05) and at 2 months was 54, 18, and 92 g (ExMI versus control, P
      <0.05) in the FES, ExMI, and control groups, respectively. Finally, 6 months
      later, the average 24-hour leakage weight was less than 10 g in all groups.
      Quality-of-life measures decreased after surgery, but gradually improved over
      time in all groups. No complications were noted in any of the groups.
      CONCLUSIONS: ExMI and FES therapies offered earlier continence compared with the
      control group after radical prostatectomy. We consider ExMI and FES to be
      recommendable options for patients who want quick improvement of postoperative
      urinary incontinence.

PMID- 14972469
TI  - Comparative study on the prevalence of clinically detectable prostate cancer in
      patients with and without bladder cancer.
AB  - OBJECTIVES: To investigate the prevalence of prostate cancer in patients with a
      past or present history of bladder cancer compared with age-matched control
      subjects in population-based screening for prostate cancer. METHODS: Between 1998
      and 2000, 106 patients who were followed up in the outpatient clinic for bladder
      cancer (case cohort) and 1060 age-matched men who participated in screening for
      prostate cancer (control cohort) were enrolled in this study. Serum prostate
      specific antigen (PSA) levels were measured for all participants, and all
      participants underwent digital rectal examination (DRE). The PSA distribution and
      prevalence rate of prostate cancer were compared between these two cohorts.
      RESULTS: The serum PSA levels were significantly greater in the case cohort than
      in the control cohort. The detection rate of prostate cancer was 12.3% (13 of
      106) and 1.5% (16 of 1060) in the case and control cohorts, respectively. The
      biopsy compliance for those with abnormal PSA and/or DRE findings was
      significantly lower (31%) in the control cohort than in the case cohort (84%). If
      all those in the control cohort with abnormal PSA and/or DRE findings had
      undergone prostate biopsies, another 26 cases of prostate cancer might have been
      detected. The expected detection rate of prostate cancer in the control cohort
      was high at 4.0% (42 of 1060); however, this was still significantly lower than
      that in the case cohort. CONCLUSIONS: Patients with a present or past history of
      bladder cancer could be a high-risk group for developing or having prostate
      cancer. Additional studies should be conducted to confirm this.

PMID- 14972470
TI  - Sexual functioning and quality of life after prostate cancer treatment:
      considering sexual desire.
AB  - OBJECTIVES: To evaluate whether the relationship between sexual desire and
      quality of life (QOL) is moderated by sexual functioning in 91 men who had
      received treatment for localized prostate cancer within the past 18 months.
      METHODS: Items from the University of California, Los Angeles, Prostate Cancer
      Index and Expanded Prostate Cancer Index Composite were used to assess sexual
      factors, and the Functional Assessment of Cancer Therapy--General Module was
      administered to evaluate QOL. Education, income, and the Charlson comorbidity
      index were significantly related to QOL and controlled in all analyses. We tested
      a moderated regression model to predict QOL. RESULTS: Although a main effect was
      detected for sexual functioning, the interaction of sexual desire and sexual
      functioning added a significant amount to the explained variance in QOL. Post hoc
      tests of moderation revealed that men with lower sexual functioning had
      significantly lower QOL scores as the level of sexual desire increased,
      suggesting that desire in the absence of adequate functioning may result in
      poorer QOL. Additionally, a tendency was found for men with better sexual
      functioning to have higher QOL scores as the level of sexual desire increased.
      CONCLUSIONS: The results of our study suggest that both sexual desire and sexual
      functioning are necessary for optimal QOL and highlight the utility of
      considering these two facets of sexuality independently to maximize the
      prediction of variance in QOL scores.

PMID- 14972471
TI  - High incidence of inguinal hernia after radical retropubic prostatectomy.
AB  - OBJECTIVES: To assess the incidence of, and risk factors for, inguinal hernia
      after retropubic radical prostatectomy compared with after pelvic lymph node
      dissection and total cystectomy. METHODS: A total of 155 radical prostatectomies,
      35 pelvic lymph node dissections, and 56 total cystectomies were included in this
      study. We reviewed the charts retrospectively and evaluated the incidence of, and
      risk factors for, inguinal hernia after surgery using Kaplan-Meier plots and a
      Cox proportional hazard model. RESULTS: Of 155 patients in the radical
      prostatectomy group, 35 patients in the pelvic lymph node dissection group, and
      56 patients in the cystectomy group, 33 (21.3%), 4 (11.4%), and 3 (5.4%),
      respectively, developed inguinal hernias during follow-up. In the radical
      prostatectomy group, 27 (81.8%) of the 33 patients developed inguinal hernia
      within 2 years postoperatively. Multivariate Cox proportional hazard analysis
      revealed that prostatectomy group, past history of inguinal hernia, and body mass
      index of less than 23 were significant risk factors for postoperative inguinal
      hernia. CONCLUSIONS: The incidence of inguinal hernia after radical prostatectomy
      is not low. Urologists should realize that inguinal hernia is one of the major
      complications of radical prostatectomy and examine the groin preoperatively and
      postoperatively.

PMID- 14972472
TI  - Use of complementary and alternative medicine in men with family history of
      prostate cancer: a pilot study.
AB  - OBJECTIVES: To describe the use of complementary and alternative medicines (CAMs)
      among men with a family history of prostate cancer and to evaluate the
      relationship between selected sociodemographic and behavioral characteristics and
      the use of CAMs. METHODS: Unaffected brothers of men diagnosed with prostate
      cancer were asked to participate in a short computer-assisted telephone
      interview. The survey focused primarily on the use of different vitamins, herbal
      supplements, and medications, some of which are marketed for prostate health or
      prostate cancer prevention. RESULTS: A total of 111 men completed the survey,
      representing 66% of eligible study subjects. Of the 111 men, 61 (55%) reported
      currently taking some form of CAM, with 30% taking a vitamin or supplement
      purported to have prostate-specific benefits. The prevalence of CAM use generally
      increased with increasing age; however, men who were younger than their affected
      brother at the time of the diagnosis of prostate cancer were more likely to use
      CAMs than were older brothers. CONCLUSIONS: Most men with a family history of
      prostate cancer take vitamins and supplements, some of which are believed to
      prevent future cancer occurrence. The results of this study and others provide
      some insight into the determinants of potentially beneficial health behaviors in
      high-risk individuals.

PMID- 14972473
TI  - Herbal and vitamin supplement use in a prostate cancer screening population.
AB  - OBJECTIVES: To report the observed usage trend of herbal and vitamin supplements
      in a population of men visiting a prostate cancer screening clinic and its
      relation to the Sexual Health Inventory for Men score and the American Urological
      Association Symptom Score (AUA-SS). METHODS: Men participating in the 2001 and
      2002 Prostate Cancer Awareness Week screening for prostate cancer were given a
      self-administered questionnaire. The questions were designed to gather background
      health information and to determine the use of prescription medications for lower
      urinary tract symptoms (LUTS), as well as the use of herbal and vitamin
      supplements. In addition, the AUA-SS and Sexual Health Inventory for Men score
      were calculated for each participant in the study. RESULTS: The number of
      questionnaires completed was 12,457. Of the completed questionnaires, 70% of the
      participants reported the use of multivitamins, and 21% reported the use of
      herbal supplements. Ten percent of all men reported the use of prescription
      medications for LUTS (AUA-SS greater than 15). Of the men reporting the use of
      prescription medications, 19% were taking finasteride, 17% doxazosin, 20%
      terazosin, 23% tamsulosin, and 22% other prescription medications. Moreover, the
      average AUA-SS was greater for the men taking herbs or supplements than for those
      who did not take herbs or supplements (P <0.001). Nonetheless, the Sexual Health
      Inventory for Men score did not show a positive correlation between the intake of
      alternative medications and the severity of erectile dysfunction. CONCLUSIONS: We
      observed that a substantial proportion of men with LUTS participating in a
      national prostate cancer screening program were not taking prescription
      medications for these symptoms. Furthermore, we observed that men taking herbs or
      vitamin supplements tended to have higher AUA scores. Additional investigation is
      warranted into the reason some men are not receiving standard prescription
      medications for LUTS and whether reliance on alternative treatments is playing a
      role in this phenomenon.

PMID- 14972474
TI  - Epididymitis after prostate brachytherapy.
AB  - OBJECTIVES: To analyze the incidence, time-course, and potential predisposing
      factors for what was clinically diagnosed as postimplant epididymitis. METHODS:
      Of 517 patients randomized and treated on two treatment protocols, with a planned
      total accrual of 1200, 5 patients were identified who developed clinically
      diagnosed epididymitis after iodine-125 or pallidium-103 prostate brachytherapy.
      Implants were performed by standard techniques, using a modified peripheral
      loading pattern. Perioperative antibiotics (cefazolin and ciprofloxacin) were
      given to 258 patients, according to physician preference. Treatment-related
      morbidity was monitored by mailed questionnaires, using standard American
      Urological Association (AUA) and Radiation Therapy Oncology Group criteria at 1,
      3, 6, 12, and 24 months. Patients who did not respond to the mailed
      questionnaires were interviewed by telephone. Although the patients were not
      queried specifically regarding epididymitis, its occurrence was noted when
      discovered in the course of follow-up examinations. RESULTS: Postimplant
      epididymitis occurred in 5 (1%) of 517 consecutive brachytherapy patients. None
      of the 5 patients had had a prior history of orchitis, epididymitis, vasectomy,
      or preimplant catheterization. The symptoms of epididymitis first appeared at 4,
      7, 10, 150, and 300 days after implantation. Patients with epididymitis had
      prostate volumes, preimplant AUA scores, and ages typical of other implant
      patients. No association was apparent between postimplant epididymitis and the
      degree of implant-related prostate swelling or the number of seeds implanted.
      Only the preimplant AUA score predicted for epididymitis, but 2 of the 5 patients
      had low scores. Only 1 (0.4%) of the 258 patients who received perioperative
      antibiotics developed epididymitis, and 4 (1.5%) of the 259 patients with
      prophylactic antibiotics developed epididymitis. CONCLUSIONS: Epididymitis is an
      uncommon postimplant complication occurring in 1% of a large patient cohort. That
      epididymitis patients had greater preimplant AUA scores is consistent with a
      retrograde infection route, at least in some cases.

PMID- 14972475
TI  - High-intensity focused ultrasound for the treatment of localized prostate cancer:
      5-year experience.
AB  - OBJECTIVES: To report on our 5-year results with transrectal high-intensity
      focused ultrasound (HIFU) in the treatment of localized prostate cancer. HIFU
      delivers high energy, causing rapid coagulation necrosis of tissue within the
      target area without damaging the surrounding tissue. METHODS: A total of 146
      patients with biopsy-proven Stage T1-T2N0M0 prostate cancer have been treated
      using the Ablatherm device. All patients had a prostate-specific antigen (PSA)
      level of 15 ng/mL or less and a Gleason score of 7 or less (inclusion criteria).
      The mean follow-up was 22.5 months (range 4 to 62) and included PSA measurement
      and control sextant biopsies. RESULTS: The median PSA nadir 3 months after
      treatment was 0.07 ng/mL (range 0 to 5.67). The median PSA level after a follow
      up of 22 months was 0.15 ng/mL (range 0 to 12.11), and 87% of the patients had a
      constant PSA level of less than 1 ng/mL; 93.4% of all patients had negative
      control biopsies. One rectourethral fistula was noted after a second HIFU
      treatment in a patient with a history of hemicolectomy and repetitive anal
      fistulas. Of all the patients, 12% underwent transurethral resection after HIFU
      because of obstruction, but no severe stress incontinence (grade 2 to 3) was
      observed. Erectile function was preserved in 47.3% of patients, and the
      International Prostate Symptom Score and Quality of Life Index did not change
      from before to after treatment. CONCLUSIONS: Our results demonstrated the
      efficacy and low-associated morbidity of HIFU. HIFU does not exclude other
      treatment options and is repeatable. HIFU seems to be a valid alternative
      treatment for patients who are not suitable for radical surgery.

PMID- 14972476
TI  - Optimal combinations for detection of prostate cancer: systematic sextant and
      laterally directed biopsies versus systematic sextant and color Doppler-targeted
      biopsies.
AB  - OBJECTIVES: To determine the accuracy of different combinations of biopsies in
      detecting prostate cancer. The standard sextant protocol for obtaining prostate
      biopsy underestimates the presence of prostate cancer. Conversely, an increased
      cancer detection rate has been obtained with additional laterally directed
      biopsies. The results of the studies dedicated to transrectal color Doppler (CD)
      sonography have shown that it might detect neoplastic lesions with no
      corresponding gray-scale abnormality. METHODS: A total of 120 consecutive
      patients underwent sextant biopsy with additional biopsy cores taken from the
      lateral peripheral zone (four to six cores, depending on the prostate volume) and
      CD-guided biopsy. The sensitivity of laterally directed, CD-guided, and different
      combinations of biopsies was compared. Various patient, clinical, and pathologic
      factors were compared, and multivariate analysis was performed to assess the
      strongest predictor of cancer detection. RESULTS: Cancer was detected in 43
      (35.8%) of 120 patients. The combination of sextant biopsy with laterally
      directed cores gained sensitivity to 56.6% compared with 67.4% obtained in the
      regimen that combined sextant and CD-guided biopsy. The CD regimen detected
      cancer in 11 additional patients. However, the differences in the detection rates
      of these combinations were not statistically significant (P = 0.797). The results
      of multivariate analysis showed that sextant biopsy and laterally directed cores
      were the strongest predictors of cancer detection (odds ratio 8.356 versus
      49.282; 95% confidence interval 1.698 to 41.114 versus 10.508 to 231.130).
      CONCLUSIONS: The regimen that included sextant and CD-guided biopsy was the most
      sensitive. However, only standard sextant and laterally directed biopsies were
      statistically significant predictors of cancer detection on biopsy.

PMID- 14972477
TI  - Epididymitis after transrectal ultrasound-guided needle biopsy of prostate gland.
AB  - OBJECTIVES: To evaluate the incidence, predisposing factors, and time-course of
      epididymitis after transrectal ultrasound-guided (TRUS) needle biopsy of the
      prostate gland. METHODS: A total of 739 consecutive patients underwent TRUS
      guided biopsy of the prostate gland from January 2000 through December 2002 using
      a systematic approach, 18-gauge needles, and antibiotic prophylaxis. A median of
      9 biopsies was obtained per patient (range 4 to 16). All cases of epididymitis
      occurring within 6 months of biopsy were attributed to the TRUS procedure. The
      parameters evaluated for epididymitis included patient age, prostate-specific
      antigen, prostate volume, prostate-specific antigen density, number of biopsies
      obtained, and number of biopsies positive for malignancy. RESULTS: Five patients
      (0.7%) developed biopsy-related epididymitis with a median onset of 85 days
      (range 13 to 143) after biopsy. Patients developing epididymitis were
      statistically older, with a trend for a greater number of prostate biopsies (P =
      0.071 on linear regression analysis). Only 1 patient developed epididymitis
      within 3 weeks of biopsy. All cases of epididymitis responded to therapeutic
      antibiotics. CONCLUSIONS: Epididymitis after TRUS-guided biopsy is a relatively
      uncommon event, with an incidence of approximately 1% and an onset of weeks to
      months after the procedure. Patients who developed epididymitis were
      statistically older, with a trend for a greater number of prostate biopsies
      taken.

PMID- 14972478
TI  - Prostate-specific antigen velocity at low prostate-specific antigen levels as
      screening tool for prostate cancer: results of second screening round of ERSPC
      (ROTTERDAM).
AB  - OBJECTIVES: To study retrospectively whether the prostate-specific antigen (PSA)
      velocity, that is, the change in PSA level over time, might serve as a screening
      tool in this PSA range. It is estimated that 40% of detectable prostate cancers
      are present in men with a PSA level of 4.0 ng/mL or less. Digital rectal
      examination and/or transrectal ultrasonography have been used as screening tools
      at these low PSA levels, but this approach is not very efficient. METHODS: The
      possible predictors (including PSA velocity) for biopsy outcome were studied
      using univariate and multivariate logistic regression analysis in 774 men who
      underwent biopsy between November 1997 and January 2002 in the second screening
      round of the European Randomised Study of Screening for Prostate Cancer (ERSPC).
      The clinical stage of the tumors was determined, and the Gleason scores of the
      biopsies were studied. RESULTS: A total of 149 cancers were found (positive
      predictive value 19.2%). The odds ratio for the PSA velocity determined by
      univariate logistic regression analysis was 2.2 (95% confidence interval 0.7 to
      6.9, P = 0.19) and was 0.73 (95% confidence interval 0.20 to 2.6, P = 0.64) by
      multivariate analysis. The distribution of the clinical stage of the detected
      tumors was 64.4% T1c, 32.2% T2, and 3.4% T3. The biopsy Gleason score was 6 in
      84.5%, 7 in 14.2%, and 8 in 1.3%. CONCLUSIONS: The number of cancers detected in
      this study and the distribution of clinical stage and biopsy Gleason score
      confirmed that a relatively large proportion of potentially curable cancers can
      be found in the low PSA ranges. The PSA velocity did not appear to be a useful
      screening tool for the identification of these cancers.

PMID- 14972481
TI  - Prostate-specific antigen change in the European Randomized Study of Screening
      for Prostate Cancer, section Rotterdam.
AB  - OBJECTIVES: To determine the prostate-specific antigen (PSA) velocity, PSA slope,
      and PSA doubling time (PSADT) in men with positive biopsies, negative biopsies,
      and no biopsy indications 4 years after an initial screening; and to use this
      information to improve the test characteristics in the early detection of
      prostate cancer and provide normal values for these parameters in screened men
      with and without evidence of prostate cancer. METHODS: Within the European
      Randomized Study of Screening for Prostate Cancer, section Rotterdam, we
      identified 9575 men with a second determination of PSA 4 years after the initial
      screening. These men were divided into three groups: men with positive biopsies,
      negative biopsies, and no biopsy indications in the second round (PSA less than
      3.0 ng/mL). The predictive values of PSA dynamics for detection of prostate
      cancer were calculated. RESULTS: The mean PSA velocity of men with prostate
      cancer was 0.62 ng/mL/yr versus 0.46 ng/mL/yr for men with a negative biopsy (P =
      0.001). The mean PSADT for men with prostate cancer was 5.1 years and for those
      with a negative biopsy it was 6.1 years (P = 0.002). The PSADT for men with no
      indication for biopsy was 25.1 years. However, receiver operating characteristic
      analyses revealed only a moderate value for these test parameters in predicting
      biopsy outcome. CONCLUSIONS: The mean values of PSA velocity, PSA slope, and
      PSADT in a rescreened population differed significantly between men with and
      without prostate cancer. However, in predicting the biopsy outcome, the PSA
      dynamics were of limited value.

PMID- 14972482
TI  - Analysis of biochemical bone markers as prognostic factors for survival in
      patients with hormone-resistant prostate cancer and bone metastases.
AB  - OBJECTIVES: To investigate the prognostic value of some conventional bone markers
      and a number of other factors in terms of the survival of patients with hormone
      resistant prostate cancer and bone metastases treated with chemotherapy. METHODS:
      The data of 141 patients were analyzed to verify the influence of the following
      factors on survival: bone-alkaline phosphatase, type I collagen propeptide, the
      carboxyterminal telopeptide of type I collagen, the urinary calcium/creatinine
      ratio, patient age, Karnofsky performance status, pathologic grade, duration of
      response to primary hormonal therapy, prostate-specific antigen, hemoglobin,
      lactate dehydrogenase, and extent of bone disease. RESULTS: When all the
      variables were simultaneously analyzed using the multivariate proportional hazard
      model, only Karnofsky performance status (P <0.005) and duration of response to
      primary hormonal therapy (P <0.0001) remained statistically significant.
      CONCLUSIONS: The results of this study suggest that bone-alkaline phosphatase,
      type I collagen propeptide, the carboxyterminal telopeptide of type I collagen,
      and the urinary calcium/creatinine ratio are not prognostic of survival in
      patients with hormone-resistant prostate cancer and bone metastases treated with
      chemotherapy.

PMID- 14972483
TI  - Radical prostatectomy lowers plasma vascular endothelial growth factor levels in
      patients with prostate cancer.
AB  - OBJECTIVES: To measure the change in plasma vascular endothelial growth factor
      (VEGF) levels after radical prostatectomy (RP) and to examine the association of
      pre-RP VEGF levels with known prognostic factors. METHODS: Plasma was collected
      from patients in two separate cohorts. The first cohort included 86 patients who
      consented to give blood before and after RP. The second cohort consisted of 280
      plasma samples, obtained from untreated patients with clinically localized
      prostate cancer. Plasma VEGF levels were measured by enzyme-linked immunosorbent
      assay. The change in plasma VEGF before and 6 to 8 weeks after RP was analyzed
      using a Wilcoxon signed rank test. The associations between the pre-RP VEGF
      levels and prognostic factors were assessed with the Spearman correlation
      coefficient and the Kruskal-Wallis test. RESULTS: In a cohort of 86 patients with
      clinically localized prostate cancer, the median preoperative VEGF level was 49.8
      pg/mL. The median level 1 month after surgery was significantly lower at 39.1
      pg/mL (P = 0.006, 20% decrease). A repeat analysis 6 months or more after surgery
      demonstrated that the percentage of decrease in the plasma VEGF levels persisted.
      Plasma VEGF levels were also measured in a separate cohort of 280 patients with
      localized prostate cancer and demonstrated no statistically significant
      association with risk groups or known tumor-associated prognostic factors.
      CONCLUSIONS: These results suggest that the prostate gland itself may be a
      significant source of systemic VEGF and raises the possibility that elevated
      plasma VEGF levels could be a reflection of prostatic VEGF production.

PMID- 14972484
TI  - Invasion of seminal vesicles by adenocarcinoma of the prostate: PSA outcome
      determined by preoperative and postoperative factors.
AB  - OBJECTIVES: To determine which preoperative and postoperative factors were
      predictive of the time to prostate-specific antigen (PSA) failure after radical
      retropubic prostatectomy (RRP) for patients with seminal vesicle invasion (SVI).
      SVI by prostate cancer is associated with high PSA failure rates after RRP and
      subsequent distant metastases. METHODS: Between 1988 and 2002, 1697 patients with
      prostate cancer underwent RRP at Brigham and Women's Hospital, of whom 103 (6%)
      had SVI. Cox regression multivariable analysis was used to determine whether the
      preoperative PSA level, prostatectomy Gleason score, margin status, or presence
      of extraprostatic extension was predictive of the time to postoperative PSA
      failure. Estimates of PSA outcome were made using the actuarial method of Kaplan
      and Meier for patients who had none, all, or at least one of the factors that
      predicted for the time to postoperative PSA failure. RESULTS: The statistically
      significant categorical predictors of the time to PSA failure after RRP in
      patients with SVI included prostatectomy Gleason score of 4+3 or greater (P =
      0.009), preoperative PSA level greater than 20 ng/dL when evaluated as a
      categorical or as a continuous variable (P = 0.002 and P = 0.001, respectively),
      and margin positivity (P = 0.075) which was of borderline significance. The 3
      year estimate of PSA control was 52% to 100%, 28%, and 0% for patients with
      negative margins, preoperative PSA less than 20 ng/dL, and prostatectomy Gleason
      score of 3+4 or less versus having one to two or all three predictors of the time
      to postoperative PSA failure. CONCLUSIONS: The PSA outcome after RRP for patients
      with SVI varies depending on the preoperative PSA level, prostatectomy Gleason
      score, and margin status.

PMID- 14972485
TI  - Radical retropubic prostatectomy in men younger than 45 years diagnosed during
      early prostate cancer detection program.
AB  - OBJECTIVES: To evaluate the incidence and outcome of prostate cancer in men
      younger than 45 years of age treated with radical retropubic prostatectomy after
      screening in an early prostate cancer detection program. METHODS: Our study group
      comprised 19,302 men younger than 45 years old who participated in this program.
      The indications for prostate biopsy were a prostate-specific antigen (PSA) level
      of 1.25 ng/mL or greater and a percent-free PSA value of 18% or less. Patients
      with prostate cancer underwent nerve-sparing radical retropubic prostatectomy.
      Intraoperative and early postoperative complications, clinical and pathologic
      stage, Gleason score, and surgical margins were reviewed retrospectively. In
      addition, potency, continence, and biochemical recurrence were assessed at the
      last follow-up visit. RESULTS: Of the study population eligible for prostate
      biopsy (1027 patients), only 175 (17%) consented to undergo the procedure (mean
      PSA 3.8 ng/mL). Twenty-eight men were diagnosed with prostate cancer,
      corresponding to 0.14% of the screened population and 16% of the biopsied
      patients. Twenty-six patients agreed to undergo radical retropubic prostatectomy.
      Pathologic examination revealed organ-confined disease in 22 (84.6%) and
      extraprostatic extension in 4 (15.4%). Positive surgical margins were seen in 2
      patients (7.7%). The Gleason score was 7 or greater in 11 (42.3%) and 6 or less
      in 15 patients (57.7%). During a mean follow-up period of 15.8 months (range 3 to
      36), all patients were continent, and 13 of the 16 patients with a follow-up of
      12 months or longer were potent. CONCLUSIONS: In a large screening population
      younger than 45 years old, 16% of biopsied patients were positive for prostate
      cancer. These tumors were clinically significant but of a low stage and therefore
      potentially curable by surgery.

PMID- 14972486
TI  - Targeting FSH in androgen-independent prostate cancer: abarelix for prostate
      cancer progressing after orchiectomy.
AB  - OBJECTIVES: To determine the efficacy of the gonadotropin-releasing hormone
      antagonist abarelix in patients with androgen-independent prostate cancer
      progressing after orchiectomy and to measure its effect on serum follicle
      stimulating hormone (FSH). METHODS: Sixteen patients with prostate cancer
      progressing after orchiectomy received abarelix-depot 100 mg by intramuscular
      injection on days 1, 15, and 29 and then every 28 days for up to 24 weeks (52
      weeks in patients who met the criteria for a prostate-specific antigen [PSA]
      response after 24 weeks). PSA response was the primary endpoint and was defined
      as a 50% reduction confirmed 4 weeks later. The time to progression and effect of
      therapy on serum FSH were secondary endpoints. RESULTS: No patient met the
      criteria for a PSA response. Five patients (31%, 95% confidence interval 11% to
      58%) experienced confirmed reductions in the PSA level ranging from 9.3% to
      31.8%. At the end of the six cycles of therapy, 6 patients remained stable
      without PSA progression or other signs of disease progression. The median time to
      progression was 12 weeks (95% confidence interval 6 to 18). The mean serum FSH
      concentration declined after 4 weeks of study treatment by nearly 90% from a
      baseline of 45.1 IU/L (95% confidence interval 34.0 to 56.2) and remained
      suppressed throughout the observation period. Treatment was well tolerated, with
      one grade 3 allergic reaction. CONCLUSIONS: Treatment with abarelix in patients
      with androgen-independent prostate cancer after orchiectomy results in marked
      reduction in circulating FSH. None of the patients met the PSA response criteria;
      nonetheless, minor reductions in serum PSA were observed in 5 of 16 patients.

PMID- 14972487
TI  - Effect of testosterone supplementation on sexual function in hypogonadal men with
      erectile dysfunction.
AB  - OBJECTIVES: To evaluate the impact of normalization of testosterone levels in men
      with documented hypogonadism and erectile dysfunction on erectile function and
      sexual satisfaction. Although the data support the role of testosterone in the
      preservation of libido and nocturnal erectile function, the evidence supporting
      the use of testosterone supplementation in hypogonadal men with erectile
      dysfunction is weak. METHODS: This analysis used two validated questionnaires,
      the International Index of Erectile Function and the Erectile Dysfunction
      Inventory of Treatment Satisfaction, in a serial fashion at baseline (before
      treatment) and 1, 3, and 6 months after the achievement of a therapeutic
      testosterone level. RESULTS: A total of 32 men met all inclusion criteria; 69% of
      men achieved therapeutic testosterone levels using transdermal testosterone gel,
      19% required a transdermal patch, and 12% required intramuscular delivery.
      Statistical significance was reached for the difference between the baseline and
      1-month International Index of Erectile Function erectile function domain score
      and all post-treatment International Index of Erectile Function libido scores. A
      steady decrease occurred in the Erectile Dysfunction Inventory of Treatment
      Satisfaction scores from the 1 to 6-month values that reached statistical
      significance. CONCLUSIONS: In men with documented hypogonadism and erectile
      dysfunction, normalization of serum testosterone levels was associated with only
      short-term improvement in erectile function and sexual satisfaction. The use of
      testosterone supplementation in this population for the treatment of erectile
      dysfunction is questionable.

PMID- 14972490
TI  - Late urologic effects after adjuvant irradiation in stage I endometrial
      carcinoma.
AB  - OBJECTIVES: To evaluate the incidence and type of incontinence after external
      beam radiotherapy (RT) and brachytherapy. Distinct late effects on the urinary
      bladder can occur and are frequently mild after adjuvant RT for Stage I
      endometrial carcinoma. Not all side effects that impair quality of life (eg,
      urinary incontinence) are classified in the commonly used grading system.
      METHODS: Forty-one patients were evaluated for newly occurred urinary
      incontinence after adjuvant RT. The mean follow-up was 64.8 months, and the mean
      age was 62.1 years. The validated incontinence score from Gaudenz was used.
      Additionally, quality-of-life questions were asked. RESULTS: Overall, 22 (53.7%)
      of 41 patients complained of urinary incontinence. Urge incontinence was
      classified in 45.5% (10 of 22 patients) and stress urinary incontinence in 54.5%
      (12 of 22 patients). CONCLUSIONS: The onset of stress urinary incontinence after
      brachytherapy can be explained by anatomic findings, such as adverse affects to
      the nerve supply of the rhabdosphincter. According to our results, the exposure
      to additional external beam RT can cause urge incontinence. Patients and doctors
      must be aware that urinary incontinence, with an occurrence rate of more than
      50%, represents the most common side effect after surgery and RT for Stage I
      endometrial carcinoma. We conclude that, depending on the type of RT, a stress
      incontinence rate of 24.4% and an urge incontinence rate of 29.2% is possible.

PMID- 14972491
TI  - Percutaneous embolization of varicoceles: outcomes and correlation of semen
      improvement with pregnancy.
AB  - OBJECTIVES: To assess the technical feasibility and compare the semen quality in
      men with or without pregnancy after percutaneous embolization of varicoceles in
      the management of infertility. METHODS: The records of 102 patients who underwent
      retrograde varicocele embolization between January 1997 and January 2002 were
      reviewed through the Hospital Information Support System. Infertility was the
      indication for embolization in 71 cases. The present study consisted of this
      group of patients. The size of the varicoceles, the size of the testis, the pre
      embolization semen analysis parameters, the technical details of embolization
      procedure, any anomalous vessels seen on venography, and, if unsuccessful, the
      reason for failure of the procedure were noted. A record of postembolization
      semen parameters (at least two) was made. Patients were divided into four groups
      depending on the pre-embolization semen density, and a correlation of this was
      assessed with improvements in morphology and motility. Follow-up was performed
      using a questionnaire to evaluate the success rate of the procedure,
      complications, and any treatment for infertility by the patient or his partner
      after the procedure. Patients who had a successful pregnancy were compared with
      those who did not to determine the correlation between the changes in semen
      quality and pregnancy rate. RESULTS: Between January 1997 and January 2002, 71
      patients underwent retrograde varicocele embolization, using an embolizing coil,
      for infertility. In 68 (95.7%), it was technically successful. Nineteen patients
      (26.7%) had various anomalous vessels on venography. A statistically significant
      improvement (P = 0.002) was noted in the motility parameters in patients with a
      pre-embolization semen density between 10 and 30 million/mL. All patients were
      followed up by questionnaire. Follow-up was possible in 51 patients (75%). One
      patient had varicocele recurrence and underwent open inguinal surgical ligation.
      Of 45 patients, the partners of 18 (40%) had a successful pregnancy. A comparison
      of the postembolization semen quality between those with and without a successful
      pregnancy found no correlation between the changes in the semen parameters and
      the pregnancy rate. CONCLUSIONS: Varicocele embolization is a technically
      feasible, minimally invasive, outpatient procedure that improves semen quality
      significantly in patients with a pre-embolization semen density of 10 to 30
      million/mL. However, no correlation was found between the improvements in semen
      quality and the pregnancy rate.

PMID- 14972492
TI  - Ureteral reimplantation for vesicoureteral reflux: comparison of minimally
      invasive extravesical with transvesical and conventional extravesical techniques.
AB  - OBJECTIVES: To analyze and compare the different ureteral reimplantation
      techniques to clarify the decision making for surgical treatment of
      vesicoureteral reflux. METHODS: From July 1995 to December 2000, 218 patients
      underwent antireflux surgery. The first 92 cases (143 ureters) were performed
      with the transvesical technique of Cohen (group 1), the next 37 cases (49
      ureters) with the conventional extravesical technique (group 2), and the last 89
      cases (113 ureters) with the new minimally invasive technique (group 3). The
      surgical time, length of hospital stay, postoperative side effects, frequency of
      pain control, and voiding cystogram findings to ensure the cessation of reflux
      for all patients were retrospectively analyzed. RESULTS: The success rates were
      similar among the different procedures. All patients in group 1 required a
      suprapubic cystostomy, and three had blood clot retention. Four patients in group
      2 had bladder inefficiency. The surgical time ranged from 139 to 181 minutes in
      group 1, 58 to 94 minutes in group 2, and 40 to 61 minutes in group 3. The length
      of hospital stay ranged from 2.8 to 5.5 days in groups 1 and 2, and no hospital
      stay was needed in group 3. The frequency of analgesic administration was
      significantly less in group 2 compared with group 1; however, no analgesia was
      required in group 3. CONCLUSIONS: The results from our comparison show that the
      minimally invasive technique can be used as a simple and highly effective
      interventional procedure with less morbidity for the patient.

PMID- 14972495
TI  - Hand-assisted laparoscopic resection of the massive autosomal dominant polycystic
      kidney.
AB  - Laparoscopic nephrectomy provides many advantages over open nephrectomy,
      including pain reduction, hospitalization, and superior cosmesis. However, the
      bulkiness of massively enlarged polycystic kidneys may preclude access to the
      renal hilum and therefore prevent safe ligation and division of the renal
      vascular supply. We describe a hand-assisted technique that facilitates the
      resection of the massively enlarged kidney.

PMID- 14972496
TI  - Robotic-assisted laparoscopic sacrocolpopexy for treatment of vaginal vault
      prolapse.
AB  - INTRODUCTION: To describe and demonstrate the use and benefit of robotic-assisted
      laparoscopic sacrocolpopexy in the treatment of posthysterectomy vaginal vault
      prolapse. TECHNICAL CONSIDERATIONS: The procedure combines the use of standard
      laparoscopy with the daVinci robotic system. The patient is placed in the dorsal
      lithotomy position. One camera port, two robotic ports, and two standard
      laparoscopic ports are placed transperitoneally. Standard laparoscopic
      dissection, in combination with an intravaginal retractor, is used for initial
      anterior and posterior vaginal mobilization and exposure of the sacral
      promontory. The daVinci robot is then docked and used to suture a silicone Y
      shaped graft from the vagina to the sacral promontory. Culdoplasty, with
      plication of the uterosacral ligaments, is then performed, with the final step,
      retroperitonealization of the graft. CONCLUSIONS: A total of 5 women have
      undergone this procedure, 3 with concomitant pubovaginal sling placement. All 5
      women were discharged after 24 hours. No complications from the sacrocolpopexy
      were reported; however, 1 patient experienced transient vaginal bleeding related
      to the pubovaginal portion of the case. No recurrent anterior, posterior, or
      apical prolapse has occurred at mean of 4 months of follow-up. Using a robotic
      system for laparoscopic sacrocolpopexy facilitated precise intracorporeal suture
      placement so that the procedure could be done in a fashion similar to that of the
      open method. Robotic-assisted laparoscopic sacrocolpopexy may provide the same
      long-term durability of open sacrocolpopexy with the benefit of a minimally
      invasive approach.

PMID- 14972497
TI  - Urothelial cancer producing granulocyte colony-stimulating factor: possible
      induction of splenomegaly.

PMID- 14972498
TI  - Retroperitoneal cyst of the lienorenal ligament.

PMID- 14972499
TI  - Progressive depletion of germ cells in a man with nonmosaic Klinefelter's
      syndrome: optimal time for sperm recovery.
AB  - We describe a sequential deteriorated change of sperm count in a 30-year-old
      infertile man with nonmosaic Klinefelter's syndrome. His initial semen analysis
      revealed oligozoospermia; however, the sperm count decreased progressively, which
      resulted in azoospermia over a period of 3 years. By testicular sperm extraction,
      a few spermatozoa were recovered. We analyzed the germ cells with three-color
      fluorescence in situ hybridization, and the presence of a 46,XY lineage was
      found. We suggest that progressive depletion of germ cells might occur in men
      with nonmosaic Klinefelter's syndrome and that these men should undergo semen
      cryopreservation or sperm recovery as early as possible.

PMID- 14972500
TI  - Renal cell carcinoma invading the inferior vena cava: use of a "temporary" vena
      cava filter to prevent tumor emboli during nephrectomy.
AB  - Renal cell carcinoma with tumor thrombus extension into the inferior vena cava
      (IVC) remains a difficult operative challenge. Placement of a suprarenal
      "temporary" IVC filter, with its ease of insertion and removal, makes it the
      ideal treatment to prevent pulmonary embolism in these difficult cases. We report
      the first 2 cases of temporary suprarenal IVC filters placed at the time of
      radical nephrectomy to eliminate the possibility of perioperative pulmonary
      embolus and avoid the potential long-term sequelae of a permanent suprarenal IVC
      filter.

PMID- 14972501
TI  - Arteriovenous intracavernous post-traumatic fistula: clinical management and
      treatment by superselective embolization.
AB  - Arteriovenous intracavernous post-traumatic fistula (FAV) is a rare post
      traumatic lesion for which the first choice of treatment is superselective
      embolization. We present a case of post-traumatic fistula in a 45-year-old
      patient. The patient underwent penile blood gas analysis and color Doppler
      ultrasonography and was treated with superselective embolization with an acrylic
      co-polymer. Postoperative arteriography showed obliteration of the fistula. Color
      Doppler ultrasonography 60 days after the procedure showed reacquired physiologic
      patency of the cavernous artery with normal flow parameters. The results of this
      case confirm superselective embolization as the reference standard treatment of
      FAV. We propose the use of an acrylic co-polymer as a new, effective embolizing
      medium.

PMID- 14972502
TI  - Transperitoneal laparoscopic radical prostatectomy in patients after laparoscopic
      prosthetic mesh inguinal herniorrhaphy.
AB  - Open radical retropubic prostatectomy has been reported to be difficult or
      impossible in patients who have previously undergone laparoscopic mesh bilateral
      inguinal hernia repair. We report 2 cases of successful laparoscopic
      transperitoneal radical prostatectomy performed in patients after prosthetic mesh
      inguinal herniorrhaphy. The first patient had undergone open bilateral
      preperitoneal inguinal hernia mesh repair 5 years previously and right
      laparoscopic transabdominal preperitoneal inguinal hernia mesh repair 7 months
      previously. The second patient had undergone bilateral transabdominal
      preperitoneal mesh inguinal herniorrhaphy 1 year previously.

PMID- 14972503
TI  - Thrombotic microangiopathy in advanced prostatic carcinoma.
AB  - We report a case of acute renal failure in a man with medically treated advanced
      prostate carcinoma. Imaging suggested renal tract obstruction as the cause;
      however, the patient failed to respond to treatment with dialysis and bilateral
      nephrostomy insertion. Postmortem examination revealed the renal failure to have
      been due to severe thrombotic microangiopathy.

PMID- 14972504
TI  - Synchronous bilateral primary transitional cell carcinoma of the upper urinary
      tracts: ten patients with more than five years of follow-up.
AB  - Primary transitional cell carcinoma of synchronous bilateral upper urinary tracts
      is rare. In our patients, end-stage renal disease and renal insufficiency were
      frequently associated with bilateral upper tract transitional cell carcinoma. The
      clinical presentations of these patients were similar to that of those with
      Chinese-herb nephropathy and Balkan endemic nephropathy. Renal-sparing surgery
      should be performed for patients with adequate renal function preoperatively.
      Renal autotransplantation combined with pyeloneocystostomy was a good method for
      1 patient who was at a high risk of developing recurrent transitional cell
      carcinoma.

PMID- 14972505
TI  - Elevation of CA 19-9 in giant hydronephrosis induced by a renal calculus.
AB  - CA 19-9 is a tumor marker of pancreatic and gastrointestinal cancer. Elevation in
      nonmalignant disease is rare. The case of a patient with a partial staghorn
      calculus, giant hydronephrosis, and elevated CA 19-9 serum levels is presented.
      Open transperitoneal right-sided nephrectomy was performed. In
      immunohistochemical analysis, CA 19-9 was expressed in the renal tubular
      epithelium and the renal pelvis. During postoperative follow-up, the CA 19-9
      levels returned to normal. Hydronephrosis might cause false-positive results when
      CA 19-9 measurement is used to screen for malignant disease. Posttreatment CA 19
      9 levels of patients with hydronephrosis have to be monitored closely to safely
      exclude malignant disease.

PMID- 14972506
TI  - Urinary immunocytology for primary bladder B cell lymphoma.
AB  - Urinary immunocytology is described as a diagnostic tool in a patient with a
      primary high-grade, large-cell, B cell lymphoma of the bladder. Lymphoma cells
      were distinguished from abundant leukocytes by immunocytologic staining for CD20.
      This technique might be useful in the differential diagnosis of patients with
      chronic bladder inflammation accompanied by pyuria.

PMID- 14972507
TI  - Estrogen and phytoestrogen predispose to erectile dysfunction: do ER-alpha and ER
      beta in the cavernosum play a role?
AB  - OBJECTIVES: To investigate the functional changes in rabbit penile corpus
      cavernosum (CC) secondary to experimental hyperestrogenism and attempt to
      identify sites of immunoexpression for estrogen receptor subtypes alpha and beta
      (ER-alpha and ER-beta) in the CC. Although the role of testosterone in sexual
      function has been extensively studied in clinical settings and experimental
      animal models, the effect of hormonal modulation/imbalance arising from
      estrogenic excess has not been characterized. METHODS: Eighteen New Zealand white
      male rabbits (2.5-3.0 kg) were divided into control and two treatment groups. The
      two treatment groups were given orally 0.1 mg of estradiol valerate (estradiol
      group) or phytoestrogen, daidzein (phytoestrogen group) daily for 12 weeks. Blood
      and tissue samples were collected for hormone levels and in vitro pharmacologic
      studies. CC samples from untreated rabbits (n = 4) were cryosectioned and
      incubated with appropriate mouse monoclonal antibody for identification of ER
      alpha and ER-beta. RESULTS: Through immunohistochemistry, color signals for
      nuclear ER-alpha and ER-beta receptors were localized within the CC. Chronic
      treatment with estradiol and phytoestrogen significantly reduced the systemic
      total testosterone levels. In organ bath experiments, relaxant responses to
      acetylcholine, nitroglycerin, and nitrergic transmission were significantly
      attenuated compared with the control response. With regard to the contractile
      effect, both types of estrogen treatments significantly potentiated
      norepinephrine-induced antierectile contraction of the CC. CONCLUSIONS: These
      results indicate that estradiol treatment and chronic exposure of phytoestrogen
      may cause receptor-mediated pathophysiologic changes in erectile function,
      leading to erectile dysfunction.

PMID- 14972508
TI  - Use of argon plasma coagulation in endourology: in vitro experiments.
AB  - OBJECTIVES: To investigate different parameters influencing argon plasma
      coagulation (APC) in a fluid medium with regard to endourologic procedures. APC
      is a novel therapeutic modality of noncontact electrocoagulation that applies
      high-frequency current by way of ionized argon gas. Recent modifications for
      endoscopic application of APC have helped to establish new indication in various
      surgical fields. METHODS: Standardized experiments using an endoscopic APC device
      were performed on fresh bovine skeletal muscle in different fluid media. The
      effects of the power setting, gas flow rates, and treatment duration on the
      coagulation zones and tissue ablation were evaluated. RESULTS: The coagulation
      zones were remarkably uniform. The depths of coagulation increased significantly
      with augmented power settings and APC duration but were not dependent on gas flow
      rates. Likewise, tissue removal increased with greater power and longer
      application times but was not affected by flow rates. Tissue ablation in general
      was moderate. Different fluid media generated varying performances. CONCLUSIONS:
      Using a laboratory model, we demonstrated that APC performed in a fluid medium is
      feasible. The power setting, treatment duration, and different fluid media were
      interdependent factors affecting the performance of APC in a fluid milieu.
      However, before application of APC in endourologic procedures in humans,
      additional studies concerning safety issues are mandatory.

PMID- 14972509
TI  - Decreased Fas expression in advanced-stage bladder cancer is not related to p53
      status.
AB  - OBJECTIVES: The Fas-Fas ligand system is an important regulator of apoptosis and
      is involved in tumor development. Invasive cancers downregulate Fas expression to
      evade antitumor immune responses. Fas is a transcriptional target of p53, which
      is often mutated in bladder cancers. Therefore, Fas expression and its relation
      to p53 mutation was investigated. METHODS: Expression of Fas protein and p53
      status was studied by immunohistochemistry in 83 bladder cancer specimens. In
      addition, mRNA levels for soluble (decoy) and membrane-bound forms of Fas were
      compared between 10 bladder cancer cell lines and primary uroepithelial cells by
      quantitative TaqMan polymerase chain reaction. Mutational analysis of the death
      domain of the Fas gene was performed in all cell lines. RESULTS: Organ-confined
      tumors maintained specific Fas staining at the cell membrane and often also in
      the cytoplasm. In higher stage carcinomas, Fas expression became restricted to a
      smaller fraction of cells or was lacking entirely. The correlation of Fas
      staining with tumor stage was highly significant but no correlation to tumor
      grade or survival was found. Furthermore, no statistically significant
      relationship was observed with either the presence or lack of mutated p53
      accumulation. Membrane-bound Fas mRNA was decreased in most, and soluble Fas was
      increased in all transitional cell carcinoma lines compared with primary
      uroepithelial cells. No mutations in the death domain were detected. CONCLUSIONS:
      Fas downregulation occurring in advanced bladder cancer is unrelated to p53
      mutations. The results of immunohistochemistry and mRNA studies of soluble and
      membrane-bound Fas in transitional cell carcinoma lines support the hypothesis of
      immune evasion in advanced bladder cancer.

PMID- 14972510
TI  - Fluorescence in situ hybridization performed on exfoliated urothelial cells in
      patients with transitional cell carcinoma of the bladder.
AB  - OBJECTIVES: To evaluate comparatively fluorescence in situ hybridization (FISH)
      and cytology performed on exfoliated urothelial cells obtained from voided urine
      and bladder washings as a method of diagnosis and follow-up in patients with
      transitional cell carcinoma (TCC) of the bladder. METHODS: Thirty patients with
      confirmed bladder TCC, 10 patients enrolled in cystoscopy follow-up for previous
      bladder tumors, and 10 patients with bladders free of tumor without a previous
      history of bladder TCC underwent cytologic examination and FISH performed on
      voided urine and bladder washing specimens. The FISH probes were targeted to
      chromosomes 7 and 9. RESULTS: FISH had a sensitivity of 92% for high-grade tumors
      in both voided urine and bladder washing specimens, significantly greater than
      that of cytology at a sensitivity of 64% in voided urine and 67% in the bladder
      washing specimens (P = 0.02). The sensitivity of FISH and cytology were both low
      and not significantly different statistically from each other for the low-grade
      tumors. Monosomy of chromosome 9 correlated with early tumor recurrence. Polysomy
      of chromosomes 7 and 9 correlated with high-grade tumors (80% and 92%,
      respectively). CONCLUSIONS: According to our results, with the local
      cytopathology expertise, FISH performed on urothelial cells from voided urine has
      a sensitivity that supersedes that of cytology, making the former a valuable
      complementary method in the diagnosis and follow-up of patients with bladder TCC.

PMID- 14972511
TI  - Syndecan-1 expression in locally invasive and metastatic prostate cancer.
AB  - OBJECTIVES: To determine the significance of syndecan-1 expression, a cell
      surface heparan sulfate proteoglycan in localized and metastatic prostate cancer.
      METHODS: We performed a retrospective analysis of 76 men with Gleason sum 6 or 7
      prostate cancer treated by radical prostatectomy and a separate cohort of 75 men
      with metastatic prostate cancer. Syndecan-1 immunoreactivity was measured in
      primary prostate specimens or in samples from metastatic sites and correlated
      with patient outcome. RESULTS: Syndecan-1 was expressed in normal basal and
      secretory epithelial cells, 26% of radical prostatectomy specimens, and 35% of
      metastatic disease. No association was found between syndecan-1 positivity and
      prostate-specific antigen recurrence in the collective cohort of Gleason sum 6
      and 7 cancers. However, when stratified by Gleason sum, syndecan-1
      immunoreactivity (immunoreactivity score 150 or greater) was associated with a
      greater recurrence rate in Gleason sum 7 cancers. Expression of syndecan-1 was
      significantly greater in soft tissue than in bone metastasis (P = 0.048, Fisher's
      exact test). CONCLUSIONS: Consistent with a possible biochemical role for
      syndecan-1 in prostate cancer progression and metastasis, syndecan-1 expression
      correlated with serologic recurrence in Gleason sum 7 prostate cancer and was
      highly expressed in soft-tissue metastases.

PMID- 14972512
TI  - Aberrant expression and possible involvement of the leptin receptor in bladder
      cancer.
AB  - OBJECTIVES: To explore the expression patterns and possible involvement of leptin
      and its receptor in the pathogenesis of urinary bladder cancer, with a focus on
      transitional cell carcinoma. METHODS: Using reverse transcription-polymerase
      chain reaction, immunoblotting, and immunohistochemistry techniques, we
      correlated the expression patterns of leptin and its receptor with the occurrence
      of transitional cell carcinoma. We also applied transient transfection followed
      by BrdU labeling and immunofluorescent staining to address the effect of the
      leptin receptor on bladder cancer cell growth. RESULTS: Although leptin was not
      detected in the bladder tissue specimens, a decreased expression of the leptin
      receptor was observed in most cancer tissue specimens we analyzed. Furthermore,
      the forced expression of the leptin receptor in T24 bladder cancer cells
      prevented them from entering the S phase. CONCLUSIONS: Our data demonstrated for
      the first time that the leptin receptor is aberrantly expressed in bladder cancer
      tissue and is possibly involved in the carcinogenesis of bladder cancer.

PMID- 14972513
TI  - Detection of GSTP1 methylation in prostatic secretions using combinatorial MSP
      analysis.
AB  - OBJECTIVES: To evaluate the utility of methylation-specific polymerase chain
      reaction analysis of the pi-class glutathione-S-transferase (GSTP1) gene promoter
      in prostatic secretions for cancer detection and prognostication. METHODS:
      Prostatic secretions were obtained from a total of 100 radical prostatectomy
      specimens immediately after surgical extirpation. GSTP1 promoter methylation was
      assessed by methylation-specific polymerase chain reaction analysis using two
      different primer sets. Correlations between GSTP1 promoter methylation and
      clinical and pathologic variables were examined. RESULTS: The sensitivity for
      detection of GSTP1 methylation in prostatic secretions from men with clinically
      localized prostate cancer using two different primer sets was 76% and 54%.
      Methylation of the GSTP1 promoter was detected by both primer sets in 44% and by
      at least one primer set in 86% of the prostatic secretion specimens. The degree
      of methylation detected in the prostatic secretions was associated with the
      extent of cancer (predominant involvement of one or both sides of the gland; P =
      0.02) and increasing age (P = 0.009). CONCLUSIONS: Genomic DNA with GSTP1
      promoter methylation can be detected in prostatic secretion specimens from the
      great majority of men with localized prostate cancer. Assays of GSTP1 promoter
      methylation in prostatic massage fluid or ejaculate may therefore serve as useful
      adjuncts to existing methods for prostate cancer screening and prognostication.

PMID- 14972514
TI  - Use of gelatin matrix to rapidly repair diaphragmatic injury during laparoscopy.

PMID- 14972516
TI  - Efficacy of oral active ether lipid analogs of cidofovir in a lethal mousepox
      model.
AB  - Cidofovir (CDV) is a highly effective inhibitor of orthopoxvirus replication and
      may be used intravenously to treat smallpox or complications arising from the
      smallpox vaccine under an investigational new drug application (IND). However,
      CDV is absorbed poorly following oral administration and is inactive orally. To
      improve the bioavailability of CDV, others synthesized alkoxyalkanol esters of
      CDV and observed >100-fold more activity than unmodified CDV against cowpox,
      vaccinia, and variola virus (VARV) replication. These ether lipid analogs of CDV
      have high oral bioavailability in mice. In this study, we compared the oral
      activity of CDV with the hexadecyloxypropyl (HDP)-, octadecyloxyethyl-,
      oleyloxypropyl-, and oleyloxyethyl-esters of CDV in a lethal, aerosol ectromelia
      virus (ECTV) challenge model in A/NCR mice. Octadecyloxyethyl-CDV appeared to be
      the most potent CDV analog as a dose regimen of 5 mg/kg started 4 h following
      challenge completely blocked virus replication in spleen and liver, and protected
      100% of A/NCR mice, although oral, unmodified CDV was inactive. These results
      suggest that this family of compounds deserves further evaluation as poxvirus
      antiviral.

PMID- 14972517
TI  - Infection and RNA recombination of Brome mosaic virus in Arabidopsis thaliana.
AB  - Ecotypes of Arabidopsis thaliana supported the replication and systemic spread of
      Brome mosaic virus (BMV) RNAs. Infection was induced either by manual inoculation
      with viral RNA or by BMV virions, demonstrating that virus disassembly did not
      prevent infection. When in vitro-transcribed BMV RNAs 1-3 were used, production
      of subgenomic RNA4 was observed, showing that BMV RNA replication and
      transcription had occurred. Furthermore, inoculations of the transgenic
      Arabidopsis line that expressed a suppressor of RNA interference (RNAi) pathway
      markedly increased the BMV RNA concentrations. Inoculations with designed BMV
      RNA3 recombination vectors generated both homologous and nonhomologous BMV RNA
      RNA recombinants. Thus, all cellular factors essential for BMV RNA replication,
      transcription, and RNA recombination were shown to be present in Arabidopsis. The
      current scope of understanding of the model Arabidopsis plant system should
      facilitate the identification of these factors governing the BMV life cycle.

PMID- 14972518
TI  - Effect of partial and complete variable loop deletions of the human
      immunodeficiency virus type 1 envelope glycoprotein on the breadth of gp160
      specific immune responses.
AB  - Induction of cross-reactive cellular and humoral responses to the HIV-1 envelope
      (env) glycoprotein was examined after DNA immunization of BALB/c mice with
      gp140(89.6)-derived constructs exhibiting partial or complete deletions of the
      V1, V2, and V3 domains. It was demonstrated that specific modification of the V3
      loop (mV3) in combination with the V2-modified (mV2) or V1/V2-deleted
      (DeltaV1/V2) region elicited increased levels of cross-reactive CD8(+) T cell
      responses. Mice immunized with the mV2/mV3 or DeltaV1/V2/mV3 gp140(89.6) plasmid
      DNA were greater than 50-fold more resistant to challenge with recombinant
      vaccinia virus (rVV) expressing heterologous env gene products than animals
      immunized with the wild-type (WT) counterpart. Sera from mV2/mV3- and
      DeltaV1/V2/mV3-immunized mice exhibited the highest cross-neutralizing activity
      and displayed intermediate antibody avidity values which were further enhanced by
      challenge with rVV expressing the homologous gp160 glycoprotein. In contrast,
      complete deletion of the variable regions had little or no effect on the cross
      reactive antibody responses. The results of these experiments indicate that the
      breadth of antibody responses to the HIV-1 env glycoprotein may not be increased
      by removal of the variable domains. Instead, partial deletions within these
      regions may redirect specific responses toward conserved epitopes and facilitate
      approaches for boosting cross-reactive cellular and antibody responses to the env
      glycoprotein.

PMID- 14972519
TI  - Efficacy of genital T cell responses to herpes simplex virus type 2 resulting
      from immunization of the nasal mucosa.
AB  - Intravaginal (ivag) or intranasal (i.n.) immunization of C57BL/6J (B6) mice with
      a thymidine kinase-deficient strain (tk-) of herpes simplex virus type 2 (HSV-2)
      resulted in comparable protection of the genital epithelium and sensory ganglia
      against HSV-2 challenge. In contrast, protection of these sites was much reduced
      in i.n.-immunized compared to ivag-immunized B cell-deficient microMT mice. Fewer
      HSV-specific T cells were detected in the genital epithelium of i.n.-immunized
      compared to ivag-immunized microMT mice after HSV-2 challenge. Passive transfer
      of HSV-specific serum to immune microMT mice restored protection of these sites
      against HSV-2 challenge. These results suggest that protection of genital and
      neuronal sites may be conferred by i.n. immunization but may be more dependent on
      antibody-dependent mechanisms than the protection resulting from genital
      immunization. These results have implications for immunization strategies to
      elicit high levels of cell-mediated protection of the genital tract and sensory
      ganglia.

PMID- 14972520
TI  - Immune response in rabbit ovaries following infection of a recombinant myxoma
      virus expressing rabbit zona pellucida protein B.
AB  - In this study, we investigated the autoimmune response in rabbit ovaries
      following infection with a recombinant myxoma virus expressing rabbit zona
      pellucida protein B (MV-ZPB). A specific IgG antibody response to ZPB was
      elicited in the serum of infected rabbits and the antibody strongly bound to the
      zona pellucida of oocytes in secondary and tertiary follicles. T cell
      infiltration in the ovary was detected in a small proportion of the infected
      rabbits. In spite of this, the mean number of preovulatory and tertiary follicles
      in the ovary was significantly reduced at 30 days postinfection compared with
      that of the infected and uninfected controls. Histological analysis revealed that
      the cortex and medulla of these ovaries had accumulated a large number of
      probably luteinized cells and there were no follicles in these areas, indicating
      the ovaries were in a severe pathological condition. The data suggest that the
      delivery of ZP antigens using a recombinant myxoma virus is a prospective way to
      develop immunocontraceptive vaccines for rabbit population control, but that more
      understanding of the kinetics of the autoimmune response induced by viral
      delivery is needed.

PMID- 14972521
TI  - Epstein-Barr virus (EBV) LMP2A alters normal transcriptional regulation following
      B-cell receptor activation.
AB  - The latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV) is an
      important mediator of viral latency in infected B-lymphocytes. LMP2A inhibits B
      cell receptor (BCR) signaling in vitro and allows for the survival of BCR
      negative B cells in vivo. In this study, we compared gene transcription in BCR
      activated B cells from non-transgenic and LMP2A Tg6 transgenic mice. We found
      that the transcriptional induction and down-regulation of many genes that
      normally occurs in B cells following BCR activation did not occur in B cells from
      LMP2A Tg6 transgenic mice. Furthermore, LMP2A induced the expression of various
      transcription factors and genes associated with DNA/RNA metabolism, which may
      allow for the altered transcriptional regulation observed in BCR-activated B
      cells from LMP2A Tg6 mice. These results suggest that LMP2A may inhibit the
      downstream effects of BCR signaling by directly or indirectly altering gene
      transcription to ensure EBV persistence in infected B cells.

PMID- 14972522
TI  - The virus-associated human immunodeficiency virus type 1 Gag-Pol carrying an
      active protease domain in the matrix region is severely defective both in
      autoprocessing and in trans processing of gag particles.
AB  - We have previously demonstrated that a human immunodeficiency virus (HIV)
      chimeric Gag protein containing a partial replacement of the matrix domain by the
      viral protease domain (PR) could undergo autoprocessing with no virus particle
      production [J. Virol. 74 (2000) 3418]. To further analyze the effects of
      repositioned PR on virus particle production and Gag-Pol incorporation, we
      introduced the chimeric PR construct into a PR-negative Gag-Pol expression
      plasmid and coexpressed the resultant construct with a Pr55(gag) expression
      plasmid (pGAG) in 293T cells. Analysis indicated that the chimeric PR was similar
      to native PR in that both could prevent virus particle production in
      cotransfections with an equivalent amount of pGAG plasmid DNA, suggesting an
      efficient trans processing of Pr55(gag) by the chimeric PR. In cotransfections
      with the pGAG at a DNA ratio of 1:10 to 1:20, which resembles the normal
      intracellular expression ratio of Gag-Pol to Gag, Gag-Pol carrying the PR in the
      Gag coding region could undergo autoprocessing in cells and was incorporated into
      virus particles at a level about 20-40% of that of wild-type Gag-Pol. However,
      the incorporated chimeric Gag-Pol was unable to autocleave and unable to process
      the Gag particles properly, as mature particle-associated reverse transcriptase
      (RT) and p24(gag) proteins were barely detected. Our data strongly suggest that
      positioning an active HIV PR in the matrix region significantly affects the PR
      mediated virus particle maturation.

PMID- 14972523
TI  - Amplification of the Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8
      lytic origin of DNA replication is dependent upon a cis-acting AT-rich region and
      an ORF50 response element and the trans-acting factors ORF50 (K-Rta) and K8 (K
      bZIP).
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8
      (HHV8), has significant sequence homology to Epstein-Barr virus (EBV). In cell
      culture, HHV8 is primarily latent, and viral genes associated with lytic
      replication are not expressed. Two lytic origins of DNA replication (oriLyt) are
      present within the HHV8 genome and are composed of an AT-rich region adjacent to
      GC-rich DNA sequences. We have now identified essential cis- and trans-acting
      elements required for oriLyt-dependent DNA replication. The transient replication
      assay was used to show that two AT-rich elements, three consensus AP1
      transcription factor-binding sites, an ORF50 response element (RE), and a
      consensus TATA box motif are essential for efficient origin-dependent DNA
      replication. Transient transfection of luciferase reporter constructs indicated
      that the downstream region of the HHV8 oriLyt responds to ORF50 and suggests that
      part of the oriLyt may be an enhancer/promoter. In addition, a transient
      cotransfection-replication assay elucidated the set of trans-acting factors
      required for lytic DNA replication. These factors consist of homologues to the
      core replication proteins: ORF6 (ssDNA binding protein), ORF9 (DNA polymerase),
      ORF40-41 (primase-associated factor), ORF44 (helicase), ORF56 (primase), and
      ORF59 (polymerase processivity factor) common to all herpesviruses along with
      ORF50 (K-Rta) and K8 (K-bZIP).

PMID- 14972524
TI  - Interaction between C/EBPbeta and Tax down-regulates human T-cell leukemia virus
      type I transcription.
AB  - The human T-cell leukemia virus type I (HTLV-I) Tax protein trans-activates viral
      transcription through three imperfect tandem repeats of a 21-bp sequence called
      Tax-responsive element (TxRE). Tax regulates transcription via direct interaction
      with some members of the activating transcription factor/CRE-binding protein
      (ATF/CREB) family including CREM, CREB, and CREB-2. By interacting with their ZIP
      domain, Tax stimulates the binding of these cellular factors to the CRE-like
      sequence present in the TxREs. Recent observations have shown that CCAAT/enhancer
      binding protein beta (C/EBPbeta) forms stable complexes on the CRE site in the
      presence of CREB-2. Given that C/EBPbeta has also been found to interact with
      Tax, we analyzed the effects of C/EBPbeta on viral Tax-dependent transcription.
      We show here that C/EBPbeta represses viral transcription and that Tax is no more
      able to form a stable complex with CREB-2 on the TxRE site in the presence of
      C/EBPbeta. We also analyzed the physical interactions between Tax and C/EBPbeta
      and found that the central region of C/EBPbeta, excluding its ZIP domain, is
      required for direct interaction with Tax. It is the first time that Tax is
      described to interact with a basic leucine-zipper (bZIP) factor without
      recognizing its ZIP domain. Although unexpected, this result explains why
      C/EBPbeta would be unable to form a stable complex with Tax on the TxRE site and
      could then down-regulate viral transcription. Lastly, we found that C/EBPbeta was
      able to inhibit Tax expression in vivo from an infectious HTLV-I molecular clone.
      In conclusion, we propose that during cell activation events, which stimulate the
      Tax synthesis, C/EBPbeta may down-regulate the level of HTLV-I expression to
      escape the cytotoxic-T-lymphocyte response.

PMID- 14972525
TI  - Mutational analyses of the core domain of Avian Leukemia and Sarcoma Viruses
      integrase: critical residues for concerted integration and multimerization.
AB  - During replicative cycle of retroviruses, the reverse-transcribed viral DNA is
      integrated into the cell DNA by the viral integrase (IN) enzyme. The central core
      domain of IN contains the catalytic site of the enzyme and is involved in binding
      viral ends and cell DNA as well as dimerization. We previously performed single
      amino acid substitutions in the core domain of an Avian Leukemia and Sarcoma
      Virus (ALSV) IN [Arch. Virol. 147 (2002) 1761]. Here, we modeled the resulting IN
      mutants and analyzed the ability of these mutants to mediate concerted DNA
      integration in an in vitro assay, and to form dimers by protein-protein cross
      linking and size exclusion chromatography. The N197C mutation resulted in the
      inability of the mutant to perform concerted integration that was concomitant
      with a loss of IN dimerization. Surprisingly, mutations Q102G and A106V at the
      dimer interface resulted in mutants with higher efficiencies than the wild-type
      IN in performing two-ended concerted integration of viral DNA ends. The G139D and
      A195V mutants had a trend to perform one-ended DNA integration of viral ends
      instead of two-ended integration. More drastically, the I88L and L135G mutants
      preferentially mediated nonconcerted DNA integration although the proteins form
      dimers. Therefore, these mutations may alter the formation of IN complexes of
      higher molecular size than a dimer that would be required for concerted
      integration. This study points to the important role of core domain residues in
      the concerted integration of viral DNA ends as well as in the oligomerization of
      the enzyme.

PMID- 14972526
TI  - Linkage of human cytomegalovirus glycoprotein gO variant groups identified from
      worldwide clinical isolates with gN genotypes, implications for disease
      associations and evidence for N-terminal sites of positive selection.
AB  - Previously, we identified the glycoprotein gO gene, UL74, as a hypervariable
      locus in the human cytomegalovirus (HCMV) genome [Virology 293 (2002) 281]. Here,
      we analyze gO from 50 isolates from congenitally infected newborns, transplant
      recipients, and HIV/AIDS patients from Italy, Australia, and UK. These are
      compared to four gO groups described from USA transplantation patients [J. Virol.
      76 (2002) 10841]. Phylogenetic analyses identified seven genotypes. Divergence
      between genotypes was up to 55% and within 3%. Discrete linkage was shown between
      seven hypervariable gO and gN genotypes, but not with gB. This suggests
      interactions, while gN and gO are known to form complexes with distinct conserved
      glycoproteins gM, gH/gL, respectively, both are involved in fusogenic entry and
      exit. Codon-based maximum likelihood models showed evidence for sites of positive
      selection. Further analyses of disease relationships should take into account
      these newly defined gO/gN groups.

PMID- 14972527
TI  - Neutralizing human monoclonal antibodies to hepatitis A virus recovered by phage
      display.
AB  - Four human monoclonal antibodies (MAbs) to hepatitis A virus (HAV) were isolated
      from a phage-displayed antibody library constructed from the peripheral blood
      lymphocytes (PBLs) of HAV-immune donors. The four MAbs showed differences in
      their affinity: two (HA6, HA9) of them were dominant after four rounds of
      panning, and showed higher affinity than the other two (HA1, HA12). All four MAbs
      showed HAV-neutralizing activity in radioimmunofocus inhibition assay and their
      neutralizing activity was positively correlated with their affinities. Analysis
      of their epitope specificity by cross-competition binding assays suggested that
      HA6 and HA9 recognize extensively overlapping epitopes, which overlap with those
      of HA1 and HA12, although HA1 and HA12 recognize distinct epitopes. In addition,
      competition assays with known neutralizing murine MAbs suggested that the
      epitopes of four human MAbs extensively overlap with those of B5B3 and K34C8
      which are distinct but reside within the single, immunodominant neutralization
      site on the HAV capsid. The human MAbs (HA6 and HA9) with highest affinity may be
      useful in the immunoprophylaxis of HAV infection.

PMID- 14972528
TI  - Respiratory syncytial virus escape mutant derived in vitro resists palivizumab
      prophylaxis in cotton rats.
AB  - Palivizumab (PZ) is the only monoclonal antibody in human use against an
      infectious disease. PZ is a humanized monoclonal antibody that recognizes the
      fusion protein of respiratory syncytial virus (RSV). PZ prophylaxis reduces the
      likelihood of hospitalization for young children at risk for severe RSV
      infections. The quasispecies nature of RNA viruses allows rapid emergence of
      viruses with a selective advantage. A PZ resistant virus was selected by passage
      of RSV in the presence of PZ in cell culture. The cell culture-derived virus was
      completely resistant to PZ prophylaxis in cotton rats. The increasing use of PZ,
      and in particular, the use of PZ in immunosuppressed patients, provide
      opportunities for resistant viruses to emerge. Whether such viruses will appear
      and be of clinical significance for humans is unknown. Preclinical studies in
      cotton rats predicted the efficacy of PZ in humans; these results suggest that if
      PZ resistant viruses arise in humans, PZ prophylaxis may be ineffective.

PMID- 14972529
TI  - The high genetic variation of viruses of the genus Nairovirus reflects the
      diversity of their predominant tick hosts.
AB  - The genus Nairovirus (family Bunyaviridae) contains seven serogroups consisting
      of 34 predominantly tick-borne viruses, including several associated with severe
      human and livestock diseases [e.g., Crimean Congo hemorrhagic fever (CCHF) and
      Nairobi sheep disease (NSD), respectively]. Before this report, no comparative
      genetic studies or molecular detection assays had been developed for this virus
      genus. To characterize at least one representative from each of the seven
      serogroups, reverse transcriptase-polymerase chain reaction (RT-PCR) primers
      targeting the L polymerase-encoding region of the RNA genome of these viruses
      were successfully designed based on conserved amino acid motifs present in the
      predicted catalytic core region. Sequence analysis showed the nairoviruses to be
      a highly diverse group, exhibiting up to 39.4% and 46.0% nucleotide and amino
      acid identity differences, respectively. Virus genetic relationships correlated
      well with serologic groupings and with tick host associations. Hosts of these
      viruses include both the hard (family Ixodidae) and soft (family Argasidae)
      ticks. Virus phylogenetic analysis reveals two major monophyletic groups: hard
      tick and soft tick-vectored viruses. In addition, viruses vectored by
      Ornithodoros, Carios, and Argas genera ticks also form three separate
      monophyletic lineages. The striking similarities between tick and nairovirus
      phylogenies are consistent with possible coevolution of the viruses and their
      tick hosts. Fossil and phylogenetic data placing the hard tick-soft tick
      divergence between 120 and 92 million years ago suggest an ancient origin for
      viruses of the genus Nairovirus.

PMID- 14972530
TI  - Raji B cells, misidentified as THP-1 cells, stimulate DC-SIGN-mediated HIV
      transmission.
AB  - A number of studies examining interactions of dendritic cell (DC)-specific ICAM-3
      grabbing nonintegrin (DC-SIGN) with viral pathogens have relied on monocytic
      transfectants as models for primary DCs. Here we show that the presumed "THP-1"
      monocytic cells used in these studies are instead Raji B cells. Moreover, we
      demonstrate that true THP-1 cells do not support DC-SIGN-mediated HIV-1
      transmission, whereas human B cell lines efficiently enhance this process. These
      data indicate that there are features common to B cells and DCs that facilitate
      transmission of HIV-1 and provide new insights toward the mechanism of DC-SIGN
      mediated HIV-1 transmission.

PMID- 14972531
TI  - Identification of a novel receptor-like protein kinase that interacts with a
      geminivirus nuclear shuttle protein.
AB  - Despite extensive studies in plant virus-host interactions, the molecular
      mechanisms of geminivirus movement and interactions with host components remain
      largely unknown. A tomato kinase protein and its soybean homolog were found to
      interact specifically with the nuclear shuttle protein (NSP) of Tomato golden
      mosaic virus (TGMV) and Tomato crinkle leaf yellows virus (TCrLYV) through yeast
      two-hybrid screening and in vitro protein binding assays. These proteins,
      designated LeNIK (Lycopersicon esculentum NSP-Interacting Kinase) and GmNIK
      (Glycine max NIK), belong to the LRR-RLK (leucine rich-repeat receptor-like
      kinase) family that is involved in plant developmental processes and/or
      resistance response. As such, NIK is structurally organized into characteristic
      domains, including a serine/threonine kinase domain with a nucleotide binding
      site at the C-terminal region, an internal transmembrane segment and leucine-rich
      repeats (LRR) at the N-terminal portion. The potential significance of the NSP
      NIK interaction is discussed.

PMID- 14972532
TI  - Comparative functional characterization of the feline foamy virus transactivator
      reveals its species specificity.
AB  - Foamy virus (FV) Bel1/Tas transactivators act as key regulators of gene
      expression and directly bind DNA Bel1 response elements (BREs) in both the
      internal (IP) and 5'LTR promoters. Here, we report the mapping and the virus
      species specificity of the nonhomologous feline foamy virus (FFV) BREs in both
      promoters. The data indicate that FFV Bel1 did not bind the primate FV IP.BRE and
      that primate FV Bel1 was not capable of binding the FFV IP.BRE. In addition, we
      show that the C-terminal activation domain of FFV Bel1 does not contribute to DNA
      binding because a C-terminal trans-dominant negative FFV Bel1 mutant was still
      able to bind to both promoters.

PMID- 14972533
TI  - Porcine adenovirus type 3 E1 transcriptional control region contains a
      bifunctional regulatory element.
AB  - We identified a bifunctional regulatory element located between nt 374 and 431
      upstream of TATA box of porcine adenovirus (PAV) 3 E1A promoter. Deletion of the
      element dramatically reduced the steady-state level of E1A mRNA, but increased
      that of E1B, which lies immediately downstream of E1A. The mutant virus displayed
      defective replication at early times of infection, but replicated nearly as
      efficiently as wild-type PAV-3 at late times of infection. This defect was
      complemented with coinfecting wild-type virus in a mixed infection. The results
      indicated that the upstream activation sequences (UAS) of E1A overlap the
      upstream repression sequences (URS) of E1B, although both transcription units are
      transcribed from different promoters.

PMID- 14972534
TI  - Mouse hepatitis virus neurovirulence: evidence of a linkage between S
      glycoprotein expression and immunopathology.
AB  - Differences in disease outcome between the highly neurovirulent MHV-JHM and
      mildly neurovirulent MHV-A59 have been attributed to variations within the spike
      (S) glycoprotein. Previously, we found that MHV-JHM neurovirulence was marked by
      diminished expression of interferon-gamma (IFN-gamma) mRNA and a reduced presence
      of CD8 T cells in the CNS concomitant with heightened macrophage inflammatory
      protein (MIP)-1 transcript levels and greater macrophage infiltration relative to
      MHV-A59 infection. Here, the ability of the S and non-spike genes to regulate
      these immune responses was evaluated using chimeric viruses. Chimeric viruses
      WTR13 and S4R22 were made on MHV-A59 variant backgrounds and, respectively,
      contained the S gene of MHV-A59 and MHV-JHM. Unexpectedly, genes other than S
      appeared to modulate events critical to viral replication and survival. Unlike
      unresolving MHV-JHM infections, the clearance of WTR13 and S4R22 infections
      coincided with strong IFN-gamma transcription and an increase in the number of
      CD8 T cells infiltrating into the CNS. However, despite the absence of detectable
      viral titers, approximately 40% of S4R22-infected mice succumbed within 3 weeks,
      indicating that the enhanced mortality following S4R22 infection was not
      associated with high viral titers. Instead, similar to the MHV-JHM infection,
      reduced survival following S4R22 infection was observed in the presence of
      elevated MIP-1alpha and MIP-1beta mRNA accumulation and enhanced macrophage
      numbers within infected brains. These observations suggest that the S protein of
      MHV-JHM influences neurovirulence through the induction of MIP-1alpha- and MIP
      1beta-driven macrophage immunopathology.

PMID- 14972535
TI  - Functional expression of CD4, CXCR4, and CCR5 in glycosphingolipid-deficient
      mouse melanoma GM95 cells and susceptibility to HIV-1 envelope glycoprotein
      triggered membrane fusion.
AB  - We had previously reported that glycosphingolipids (GSL) support human
      immunodeficiency virus type 1 (HIV-1) entry. In this study, we further examined
      this issue by expressing HIV-1 receptors in GSL-deficient GM95 cells. GM95 cells
      expressing low levels of CD4 and CXCR4 or CCR5 did not support HIV-1 Env-mediated
      fusion. However, higher expression of these receptors rendered GM95 cells highly
      susceptible to fusion with cells expressing appropriate HIV-1 envelope
      glycoproteins (HIV-1 Envs). The GM95 cells exhibited a different fusion phenotype
      when compared with GSL(+) NIH3T3 cells bearing similar receptor levels. Fusion of
      GM95 targets expressing higher levels of CD4 and coreceptors occurred at 25
      degrees C and was sensitive to cholesterol depletion or disruption of the
      cytoskeleton. In contrast, the fusion threshold of NIH3T3CD4X4/R5 targets was at
      >/=28 degrees C as previously reported and was insensitive to cholesterol
      depletion or cytoskeletal network disruption. On the basis of these observations,
      we propose that target membrane GSLs support HIV-1 Env-mediated fusion at low
      density of receptors by stabilizing receptor pools in natural targets.

PMID- 14972536
TI  - Poliovirus mutants excreted by a chronically infected hypogammaglobulinemic
      patient establish persistent infections in human intestinal cells.
AB  - Immunodeficient patients whose gut is chronically infected by vaccine-derived
      poliovirus (VDPV) may excrete large amounts of virus for years. To investigate
      how poliovirus (PV) establishes chronic infections in the gut, we tested whether
      it is possible to establish persistent VDPV infections in human intestinal Caco-2
      cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut
      of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000)
      3001], were used to infect both undifferentiated, dividing cells, and
      differentiated, polarized enterocytes. A VDPV mutant excreted 36 days
      postvaccination by the patient was lytic in both types of intestinal cell
      cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs
      excreted 136, 442, and 637 days postvaccination, established persistent
      infections both in undifferentiated cells and in enterocytes. Thus, viral
      determinants selected between day 36 and 136 conferred on VDPV mutants the
      capacity to infect intestinal cells persistently. The percentage of persistently
      VDPV-infected cultures was higher in enterocytes than in undifferentiated cells,
      implicating cellular determinants involved in the differentiation of enterocytes
      in persistent VDPV infections. The establishment of persistent infections in
      enterocytes was not due to poor replication of VDPVs in these cells, but was
      associated with reduced viral adsorption to the cell surface.

PMID- 14972537
TI  - Identification of an ovine atadenovirus gene whose product activates the viral E2
      promoter: possible involvement of E2F-1.
AB  - Activation of the adenoviral E2 promoter is an early step in adenovirus gene
      expression. For members of the mast- and aviadenoviruses, this requires induction
      of the cellular transcription factor E2F by virally encoded gene products such as
      E1A, E4orf6/7 and orf22/GAM-1. The newly recognized genus atadenovirus, of which
      the ovine isolate OAdV is the prototype, lacks any sequence homology to those
      genes. To find a possible link between E2 promoter activation and OAdV gene
      expression, we utilized a screening method to search for genes within the OAdV
      genome that were capable of stimulating the viral E2 promoter. One such gene,
      E43, was identified within the proposed E4 region toward the right-hand end of
      the OAdV genome. The E43 gene product was also found to be capable of stimulating
      E2F-1-dependent gene expression. A closer inspection of the E2 promoter revealed
      the presence of a non-palindromic E2F binding site within the OAdV E2 promoter.
      Mutation of this site markedly reduced both E2F-1- and E43-dependent promoter
      activation. Moreover, a direct protein-protein interaction of the E43 gene
      product with E2F, but not with the retinoblastoma protein pRb, suggested a
      possible cooperation between these two proteins in activating the E2 promoter.
      The importance of the E43 gene product for virus replication is also underlined
      by the finding that an OAdV recombinant with a functionally inactivated E43 gene
      showed severely inhibited virus growth.

PMID- 14972538
TI  - Short deletions in nuclear targeting sequences of African cassava mosaic virus
      coat protein prevent geminivirus twinned particle formation.
AB  - Coat proteins (CPs) of geminiviruses are multifunctional proteins. Using
      transient expression experiments, we have recently identified putative sequence
      motifs of African cassava mosaic virus (ACMV) CP involved in nuclear import (NLS)
      and export (NES) (Virology 286 (2001) 373). Here, we report on the effect of
      corresponding deletion mutants in the context of infecting viruses. Since NLS and
      NES may overlap with DNA binding and multimerisation domains, we have
      investigated their effect on viral infection, particularly, on particle
      formation. All deletion mutants were infectious in Nicotiana benthamiana when co
      inoculated with DNA B, but poorly sap-transmissible. Some of the mutants showed
      reduced levels of viral single-stranded DNA (ssDNA), whereas the amount of double
      stranded DNA (dsDNA) was not greatly affected. None of these CP mutants was able
      to produce stable virus particles. In contrast, viruses with CP fused to Flag
      epitopes at the N- or C-terminus (CP:Flag or Flag:CP) were readily sap
      transmissible and formed amorphous nucleoprotein particles but only few geminate
      structures. The relevance of the identified sequences in replicating viruses with
      reference to nuclear import and export as well as to particle stability and DNA
      binding is discussed.

PMID- 14972539
TI  - Herpesvirus of turkeys: microarray analysis of host gene responses to infection.
AB  - Herpesvirus of turkeys (HVT) provides an economically important live vaccine for
      prevention of Marek's disease (MD) of chickens. MD, characterized by both
      immunosuppression and T-cell lymphoma, is caused by another herpesvirus termed
      Marek's disease virus (MDV). Microarrays were used to investigate the response of
      chicken embryonic fibroblasts (CEF) to infection with HVT. Genes responding to
      HVT infection include several induced by interferon along with others modulating
      signal transduction, transcription, scaffolding proteins, and the cytoskeleton.
      Results are compared with earlier studies examining the responses of CEF cells to
      infection with MDV.

PMID- 14972540
TI  - Bovine aortic endothelial cells are susceptible to hantavirus infection; a new
      aspect in hantavirus ecology.
AB  - Hantaviruses are enveloped RNA viruses that belong to the family Bunyaviridae.
      They are the causative agents of hemorrhagic fever with renal syndrome (HFRS) and
      hantavirus pulmonary syndrome (HPS). Hantaviruses show a worldwide distribution
      with specific rodent species as natural hosts. It is known that rodents can
      transmit the virus via feces, urine, saliva, or bites to humans. Additionally,
      antibodies against different hantaviruses were also found in domestic animals,
      For example, Danes et al. documented hantavirus-specific IgG titers in 2% of
      examined cattle [Ceskoslov. Epidemiol. Mikrobiol. Imunol. 41 (1992) 15]. In order
      to clarify the possibility of a nonrodent and nonhuman hantavirus infection, the
      susceptibility of bovine aortic endothelial cells (BAEC) to Hantavirus serotype
      Puumala infection was investigated. The hantaviral nucleocapsid protein was
      detected in 95% of infected BAEC at the fourth cell culture passage 12 weeks
      after initial infection by immunofluorescence assay (IFA). The presence of
      Puumala virus (PUU) nucleocapsid protein and the viral glycoproteins G1 and G2 in
      infected cells were additionally confirmed by Western blot analysis. The viral
      RNA genome was identified in infected BAEC cultures and in cell-free culture
      medium at the fourth passage by reverse transcription polymerase chain reaction
      (RT-PCR), verified by cDNA nucleotide sequence analysis, showing a 98-100%
      homology to the input virus. The infected BAEC cultures were shown to express
      alpha(V)beta(3)-integrin surface receptors that are known to mediate virus entry
      in human cells and revealed no major cytopathic effects (CPEs) as assayed by
      immunofluorescence staining of the cytoskeletal components actin and
      microtubules. In the present study, we documented for the first time that a
      nonrodent and nonhuman aortic endothelial cell culture of bovine origin (BAEC)
      can be efficiently infected with a hantavirus. This finding is of particular
      importance because it adds new aspects to questions dealing with host species
      barrier, viral reservoir, virus transmission, and ecology of hantaviruses.

PMID- 14972541
TI  - Genetic, biochemical, and structural characterization of a new densovirus
      isolated from a chronically infected Aedes albopictus C6/36 cell line.
AB  - We report the isolation, sequencing, biochemical, and structural characterization
      of a previously undescribed virus in a chronically infected Aedes albopictus
      C6/36 cell line. This virus is identified as a new densovirus under the
      Densovirinae subfamily of the Parvoviridae based on its biological and
      morphologic properties as well as sequence homologies, and is tentatively
      designated A. albopictus C6/36 cell densovirus (C6/36 DNV). Analysis of the 4094
      nt of the C6/36 DNV genome revealed that the plus strand had three large open
      reading frames (ORFs): a left ORF, a right ORF, and a mid-ORF (within the left
      ORF), whose potential coding capacities are 91.0, 40.8, and 41.2 kDa,
      respectively. The left ORF likely encodes the nonstructural protein NS-1, which
      contains NTP-binding and helicase domains. The right ORF likely encodes
      structural proteins, VP1 and VP2. Our analyses revealed that C6/36 DNV has a
      similar genomic organization and shares very high homology in nucleotide sequence
      and amino acid sequences with Aedes aegypti densovirus (AaeDNV) and A. albopictus
      densovirus (AalDNV), members of the genus Brevidensovirus of the Densovirinae.
      Similar to other densoviruses, C6/36 DNV has a different genomic organization and
      no recognizable sequence homology with viruses in the Parvovirinae. The three
      dimensional (3D) reconstruction of the C6/36 DNV at 15.6-A resolution by electron
      cryomicroscopy (cryoEM) revealed distinctive outer surface features not
      previously seen in other parvoviruses, indicating structural divergence of
      densoviruses, in addition to its genomic differences, while the inner surface of
      the C6/36 DNV capsid exhibits features that are conserved among parvoviruses.

PMID- 14972542
TI  - In vivo neutralization of hepatitis B virus infection by an anti-preS1 humanized
      antibody in chimpanzees.
AB  - Previously, we generated a murine monoclonal antibody (mAb), KR127, that
      recognizes amino acids (aa) 37-45 of the preS1 of hepatitis B virus (HBV). In
      this study, we have constructed a humanized version of KR127 and evaluated its
      HBV-neutralizing activity in chimpanzees. A study chimpanzee was given a single
      intravenous dose of the humanized antibody, followed by intravenous challenge
      with adr subtype of wild type HBV, while a control chimpanzee was only challenged
      with the virus. The result showed that the study chimpanzee did not develop HBV
      infection during 1 year, while the control chimpanzee was infected, indicating
      that the humanized antibody exhibited in vivo virus-neutralizing activity and
      thus protected the chimpanzee from HBV infection. In addition, the humanized
      antibody bound to the preS1 of all subtypes of HBV. We first demonstrate that an
      anti-preS1 mAb can neutralize HBV infection in vivo. This humanized antibody will
      be useful for the immunoprophylaxis of HBV infection.

PMID- 14972543
TI  - Construction and sequencing of an infectious clone of the human parvovirus B19.
AB  - Human parvovirus B19 has a nonenveloped, icosahedral capsid packaging a linear
      single-stranded DNA genome of 5.6 kb with long inverted terminal repeats (ITR) at
      both the 5' and 3' end. Previous attempts to construct a full-length B19 clone
      were unsuccessful due to deletions in the ITR sequences. We cloned the complete
      parvovirus B19 genome with intact ITRs from an aplastic crisis patient. Sequence
      analysis of the complete viral genome indicated that both 5' and 3' ITRs have two
      sequence configurations and several base changes within the ITRs compared to
      previous published sequences. After transfection of the plasmid into permissive
      cells, spliced and non-spliced viral transcripts and viral capsid proteins could
      be detected. Southern blot analysis of the DNA purified from the plasmid
      transfected cells confirmed parvovirus B19 DNA replication. Production of
      infectious virus by the B19 plasmid was shown by inoculation of cell lysate
      derived from transfected cells into fresh cells. Together, these results indicate
      the first successful production of an infectious clone for parvovirus B19 virus.

PMID- 14972544
TI  - Sequence analysis of L RNA of Lassa virus.
AB  - The L RNA of three Lassa virus strains originating from Nigeria, Ghana/Ivory
      Coast, and Sierra Leone was sequenced and the data subjected to structure
      predictions and phylogenetic analyses. The L gene products had 2218-2221
      residues, diverged by 18% at the amino acid level, and contained several
      conserved regions. Only one region of 504 residues (positions 1043-1546) could be
      assigned a function, namely that of an RNA polymerase. Secondary structure
      predictions suggest that this domain is very similar to RNA-dependent RNA
      polymerases of known structure encoded by plus-strand RNA viruses, permitting a
      model to be built. Outside the polymerase region, there is little structural
      data, except for regions of strong alpha-helical content and probably a coiled
      coil domain at the N terminus. No evidence for reassortment or recombination
      during Lassa virus evolution was found. The secondary structure-assisted
      alignment of the RNA polymerase region permitted a reliable reconstruction of the
      phylogeny of all negative-strand RNA viruses, indicating that Arenaviridae are
      most closely related to Nairoviruses. In conclusion, the data provide a basis for
      structural and functional characterization of the Lassa virus L protein and
      reveal new insights into the phylogeny of negative-strand RNA viruses.

PMID- 14972545
TI  - Avian encephalomyelitis virus nonstructural protein 2C induces apoptosis by
      activating cytochrome c/caspase-9 pathway.
AB  - The nonstructural protein 2C is highly conserved among picornaviruses and plays
      an important role in the assembly of mature virions, membrane association, and
      viral RNA synthesis. The investigation of other potential functions of
      nonstructural protein 2C from avian encephalomyelitis virus (AEV) resulted in
      identifying for the first time that the protein 2C is involved in apoptosis.
      Expression of the protein 2C on chick embryo brain (CEB) and Cos-7 cells produced
      TUNEL-positive cells characterized by a cleavage of cellular DNA and the
      formation of membrane-enclosed apoptotic bodies. Analysis of the protein 2C
      showed that the N-terminal domain containing 35 amino acid (aa) residues (between
      46 and 80 aa) is associated with apoptotic function. Transfection of the deletion
      mutant lacking this 35 aa's into CEB and Cos-7 cells failed to induce apoptosis.
      Furthermore, the protein 2C induced apoptosis in the transfected CEB and Cos-7
      cells through activation of caspase-9 rather than caspase-8 followed by
      activation of caspase-3 pathway. Analysis of the Western blots of caspase-3 and
      caspase-9 showed the characteristics of active caspase-3 and -9 in the 2C
      transfected CEB and Cos-7 cells as seen in the AEV-infected CEB cells while they
      were in the form of procaspase-3 and procaspase-9 in the 2C mutant-transfected
      cells. To further elucidate the mechanism of the 2C-induced apoptosis, the 2C
      transfected CEB and Cos-7 cells were fractionated into mitochondria and cytosol
      and subjected for Western blotting, located cytochrome c in the mitochondria as
      well as the cytosol fractions, while it was only sequestered in the mitochondrial
      fraction in the mutant 2C-transfected cells. The protein 2C was located in the
      mitochondria and cytosol of the transfected/infected CEB and transfected Cos-7
      cells, but the mutant lost its ability to localize to the mitochondria.
      Altogether, the results demonstrate that the protein 2C localized to the
      mitochondria of the transfected cells triggered the efflux of cytochrome c into
      the cytosol in turn activating the upstream caspase-9 and then the downstream
      caspase-3, thus leading to apoptosis in the cells.

PMID- 14972546
TI  - Emergence of vertebrate retroviruses and envelope capture.
AB  - Retroviruses are members of the superfamily of retroelements, mobile genetic
      elements that transpose via an RNA intermediate. However, retroviruses are
      distinct from other retroelements in that their "transposition" is not confined
      to single cells but extends to neighboring cells and organisms. As such, the
      "transposition" of these elements is defined as infection. It appears that a key
      step in the conversion of a retrotransposon into a retrovirus is the modular
      acquisition or capture of an envelope glycoprotein (Env) which facilitates
      dissemination from its initial host cell. Here we present several examples of
      retroviruses for which envelope capture has been identified. Indeed, capture may
      explain the notable conservation of env sequences among otherwise
      phylogenetically distant retroviruses. In a recent example, sequence homologies
      reported between the env of the phylogenetically distant murine leukemia viruses
      (MLV) and human T cell leukemia viruses (HTLV) argue in favor of an env capture
      by the latter. Env acquisition can provide new adaptive properties to replication
      competent viruses in addition to altering their host range. Also, the captured
      env can alter the spectrum of physiological affects of infection in new host
      cells and organisms. The elucidation of such envelope exchanges and properties
      thereof should contribute significantly to the clarification of retroviral
      phylogeny, insight into retroviral pathogenesis, and to the discovery of new
      retroviruses.

PMID- 14972547
TI  - The refined structure of Nudaurelia capensis omega virus reveals control elements
      for a T = 4 capsid maturation.
AB  - Large-scale reorganization of protein interactions characterizes many biological
      processes, yet few systems are accessible to biophysical studies that display
      this property. The capsid protein of Nudaurelia capensis omega Virus (NomegaV)
      has previously been characterized in two dramatically different T = 4 quasi
      equivalent assembly states when expressed as virus-like particles (VLPs) in a
      baculovirus system. The procapsid (pH 7), is round, porous, and approximately 450
      A in diameter. It converts, in vitro, to the capsid form at pH 5 and the capsid
      is sealed shut, shaped like an icosahedron, has a maximum diameter of 410 A and
      undergoes an autocatalytic cleavage at residue 570. Residues 571-644, the gamma
      peptide, remain associated with the particle and are partially ordered. The
      interconversion of these states has been previously studied by solution X-ray
      scattering, electron cryo microscopy (CryoEM), and site-directed mutagenesis. The
      particle structures appear equivalent in authentic virions and the low pH form of
      the expressed and assembled protein. Previously, and before the discovery of the
      multiple morphological forms of the VLPs, we reported the X-ray structure of
      authentic NomegaV at 2.8 A resolution. These coordinates defined the fold of the
      protein but were not refined at the time because of technical issues associated
      with the approximately 2.5 million reflection data set. We now report the
      refined, authentic virus structure that has added 29 residues to the original
      model and allows the description of the chemistry of molecular switching for T =
      4 capsid formation and the multiple morphological forms. The amino and carboxy
      termini are internal, predominantly helical, and disordered to different degrees
      in the four structurally independent subunits; however, the refined structure
      shows significantly more ordered residues in this region, particularly at the
      amino end of the B subunit that is now seen to invade space occupied by the A
      subunits. These additional residues revealed a previously unnoticed strong
      interaction between the pentameric, gamma peptide helices of the A and B subunits
      that are largely proximal to the quasi-6-fold axes. One C-terminal helix is
      ordered in the C and D subunits and stabilizes a flat interaction in two
      interfaces between the protein monomers while the other, quasi-equivalent,
      interactions are bent. As this helix is arginine rich, the comparable, disordered
      region in the A and B subunits probably interacts with RNA. One of the subunit
      subunit interfaces has an unusual arrangement of carboxylate side chains. Based
      on this observation, we propose a mechanism for the control of the pH-dependent
      transitions of the virus particle.

PMID- 14972548
TI  - Genetic and functional analyses of the oX174 DNA binding protein: the effects of
      substitutions for amino acid residues that spatially organize the two DNA binding
      domains.
AB  - The oX174 DNA binding protein contains two DNA binding domains, containing a
      series of DNA binding basic amino acids, separated by a proline-rich linker
      region. Within each DNA binding domain, there is a conserved glycine residue.
      Glycine and proline residues were mutated and the effects on virion structure
      were examined. Substitutions for glycine residues yield particles with similar
      properties to previously characterized mutants with substitutions for DNA binding
      residues. Both sets of mutations share a common extragenic second-site
      suppressor, suggesting that the defects caused by the mutant proteins are
      mechanistically similar. Hence, glycine residues may optimize DNA-protein
      contacts. The defects conferred by substitutions for proline residues appear to
      be fundamentally different. The properties of the mutant particles along with the
      atomic structure of the virion suggest that the proline residues may act to guide
      the packaged DNA to the adjacent fivefold related asymmetric unit, thus
      preventing a chaotic packaging arrangement.

PMID- 14972549
TI  - Immediate early genes expressed in chlorovirus infections.
AB  - Twenty-three chlorovirus genes expressed in host cells as early as 5-10 min
      postinfection (p.i.), or immediate early, were isolated and characterized. Some
      showed significant homology with those for transcriptional factors and mRNA
      processing proteins including TFIIB, helicases, mRNA capping enzyme, nucleolin,
      and bean transcription factor. Others code for (i) factors influencing
      translation such as aminoacyl tRNA synthetases and ribosomal protein, and (ii)
      unknown proteins. Enzymes involved in polysaccharide synthesis were also found.
      All transcripts of these genes had a poly(A) tail, which decreased in size after
      20 min p.i., possibly caused by the shortening by an exonuclease. Often, due to
      readthrough either from an upstream ORF or into a downstream ORF, a few extra
      transcripts for each gene appeared after 40 min p.i., suggesting a change in
      promoter selection and termination accuracy at this point. A typical TATA-box and
      a common element 5'-ATGACAA were in the promoter region of almost all of the
      immediate early genes, which may be recognized by host RNA polymerase and
      transcription factors.

PMID- 14972550
TI  - Identification of murine T-cell epitopes in Ebola virus nucleoprotein.
AB  - CD8 T cells play an important role in controlling Ebola infection and in
      mediating vaccine-induced protective immunity, yet little is known about
      antigenic targets in Ebola that are recognized by CD8 T cells. Overlapping
      peptides were used to identify major histocompatibility complex class I
      restricted epitopes in mice immunized with vectors encoding Ebola nucleoprotein
      (NP). CD8 T-cell responses were mapped to a H-2(d)-restricted epitope (NP279-288)
      and two H-2(b)-restricted epitopes (NP44-52 and NP288-296). The identification of
      these epitopes will facilitate studies of immune correlates of protection and the
      evaluation of vaccine strategies in murine models of Ebola infection.

PMID- 14972551
TI  - Complete genome sequence of the Lactococcus lactis temperate phage phiLC3:
      comparative analysis of phiLC3 and its relatives in lactococci and streptococci.
AB  - Complete genome sequencing of the P335 temperate Lactococcus lactis bacteriophage
      phiLC3 (32, 172 bp) revealed fifty-one open reading frames (ORFs). Four ORFs did
      not show any homology to other proteins in the database and twenty-one ORFs were
      assigned a putative biological function. phiLC3 contained a unique replication
      module and orf201 was identified as the putative replication initiator protein
      encoding gene. phiLC3 was closely related to the L. lactis r1t phage (73% DNA
      identity). Similarity was also shared with other lactococcal P335 phages and the
      Streptococcus pyogenes prophages 370.3, 8232.4 and 315.5 over the non-structural
      genes and the genes involved in DNA packaging/phage morphogenesis, respectively.
      phiLC3 contained small homologous regions distributed among lactococcal phages
      suggesting that these regions might be involved in mediating genetic exchange.
      Two regions of 30 and 32 bp were conserved among the streptococcal and
      lactococcal r1t-like phages. These two regions, as well as other homologous
      regions, were located at mosaic borders and close to putative transcriptional
      terminators indicating that such regions together might attract recombination.
      The conserved regions found among lactococcal and streptococcal phages might be
      used for identification of phages/prophages/prophage remnants in their hosts.

PMID- 14972552
TI  - The genome and proteome of coliphage T1.
AB  - The genome of enterobacterial phage T1 has been sequenced, revealing that its
      50.7-kb terminally redundant, circularly permuted sequence contains 48,836 bp of
      nonredundant nucleotides. Seventy-seven open reading frames (ORFs) were
      identified, with a high percentage of small genes located at the termini of the
      genomes displaying no homology to existing phage or prophage proteins. Of the
      genes showing homologs (47%), we identified those involved in host DNA
      degradation (three endonucleases) and T1 replication (DNA helicase, primase, and
      single-stranded DNA-binding proteins) and recombination (RecE and Erf homologs).
      While the tail genes showed homology to those from temperate coliphage N15, the
      capsid biosynthetic genes were unique. Phage proteins were resolved by 2D gel
      electrophoresis, and mass spectrometry was used to identify several of the spots
      including the major head, portal, and tail proteins, thus verifying the
      annotation.

PMID- 14972553
TI  - Expansion of quasispecies diversity but no evidence for adaptive evolution of
      SHIV during rapid serial transfers among seronegative macaques.
AB  - Four successive, rapid serial passages of the nonpathogenic, CCR5-tropic simian
      human immunodeficiency virus SHIV(SF162) in rhesus macaques resulted in an
      increase in acute plasma viremia with each passage and the emergence of a
      pathogenic isolate SHIV(SF162P3) in one of the passage three transfer animals
      (macaque T353). To explore the mechanism(s) underlying increased virulence of
      SHIV(SF162) upon in vivo passage, the evolution of the HIV-1 envelope gene was
      characterized in plasma and PBMC samples obtained from animals before (week 1)
      and after (week 3) the time of virus transfer. We found no evidence in support of
      adaptive evolution of the HIV gp120 during rapid serial passage; however, the
      animals which later received passage virus had more diverse quasispecies.
      SHIV(SF162P3)-like gp120 sequences were first detected in macaque T353 at week 6,
      after seroconversion. These sequence changes increased in frequency and number at
      later time points. The first sequence change conferred neutralization escape but
      not an increase in viral infectivity that could account for the apparent increase
      in replicative capacity of the later passage viruses. Collectively, our data
      argue against any host-specific adaptation of the HIV-1 envelope gp120 as the
      basis for the generation of more aggressive SHIV variants during rapid serial
      transfers in seronegative macaques, and support the model of quasispecies
      diversity as a predictor of pathogenesis. Envelope sequence changes accumulate
      principally in response to immune pressure exerted by the host, generating viral
      variants that can persist in the presence of a strong host immune response.

PMID- 14972554
TI  - The Epstein-Barr virus nuclear antigen-6 protein co-localizes with EBNA-3 and
      survival of motor neurons protein.
AB  - The Epstein-Barr virus nuclear antigen (EBNA)-6 protein is essential for Epstein
      Barr virus (EBV)-induced immortalization of primary human B-lymphocytes in vitro.
      In this study, fusion proteins of EBNA-6 with green fluorescent protein (GFP)
      have been used to characterize its nuclear localization and organization within
      the nucleus. EBNA-6 associates with nuclear structures and in immunofluorescence
      demonstrate a punctate staining pattern. Herein, we show that the association of
      EBNA-6 with these nuclear structures was maintained throughout the cell cycle and
      with the use of GFP-E6 deletion mutants, that the region amino acids 733-808 of
      EBNA-6 contains a domain that can influence the association of EBNA-6 with these
      nuclear structures. Co-immunofluorescence and confocal analyses demonstrated that
      EBNA-6 and EBNA-3 co-localize in the nucleus of cells. Expression of EBNA-6, but
      not EBNA-3, caused a redistribution of nuclear survival of motor neurons protein
      (SMN) to the EBNA-6 containing nuclear structures resulting in co-localization of
      SMN with EBNA-6.

PMID- 14972555
TI  - Generation and characterization of P gene-deficient rabies virus.
AB  - Rabies virus (RV) deficient in the P gene was generated by reverse genetics from
      cDNA of HEP-Flury strain lacking the entire P gene. The defective virus was
      propagated and amplified by rescue of virus, using a cell line that complemented
      the functions of the deficient gene. The P gene-deficient (def-P) virus
      replicated its genome and produced progeny viruses in the cell lines that
      constitutively expressed the P protein, although it grew at a slightly retarded
      rate compared to the parental strain. In contrast, no progeny virus was produced
      in the infected host when the def-P virus-infected cells that did not express the
      P protein. However, we found that the def-P virus had the ability to perform
      primary transcription (by the virion-associated polymerase) in the infected host
      without de novo P protein synthesis. The def-P virus was apathogenic in adult and
      suckling mice, even when inoculated intracranially. Inoculation of def-P virus in
      mice induced high levels of virus-neutralizing antibody (VNA) and conferred
      protective immunity against a lethal rabies infection. These results demonstrate
      the potential utility of gene-deficient virus as a novel live attenuated rabies
      vaccine.

PMID- 14972556
TI  - Evidence for conformational flexibility in the Tat-TAR recognition motif of
      cyclin T1.
AB  - Cyclin T1 (CycT1) is a cellular transcription elongation factor that also
      participates in Tat-mediated activation of several lentiviral promoters. In human
      immunodeficiency virus (HIV), CycT1 is required for Tat to bind tightly to TAR
      and interacts in the ternary complex via its Tat-TAR recognition motif (TRM). In
      the related bovine immunodeficiency virus (BIV), Tat recognizes its cognate TAR
      element with high affinity and specificity in the absence of CycT1. At both
      promoters, CycT1 recruits the Cdk9 kinase, which phosphorylates RNA polymerase II
      to generate processive transcription complexes. To examine the physical
      properties of CycT1, we purified a functional domain corresponding to residues 1
      272 and found that it possesses a stably folded core, as judged by partial
      proteolysis and circular dichroism experiments. Interestingly, the C-terminal 20
      residues corresponding to the TRM appear conformationally flexible or disordered.
      The TRM of the bovine CycT1 (bCycT1) is similarly sensitive to proteolysis yet
      differs in sequence from the human protein. In particular, bCycT1 lacks a
      cysteine at residue 261 known to be critical for HIV but not BIV ternary complex
      formation, and mutagenesis data are consistent with a proposed role for this
      cysteine in metal binding. The apparent flexibility of the TRM suggests that
      conformational rearrangements may accompany formation of CycT1-Tat-TAR ternary
      complexes and may contribute to different TAR recognition strategies in different
      lentiviruses.

PMID- 14972557
TI  - Effects of linker-insertion mutations in herpes simplex virus 1 gD on
      glycoprotein-induced fusion with cells expressing HVEM or nectin-1.
AB  - Several cell surface molecules, including HVEM and nectin-1, can serve as entry
      receptors for herpes simplex virus (HSV) and as receptors for virus-induced or
      viral glycoprotein-induced cell fusion. The viral ligand for these receptors is
      the HSV envelope glycoprotein gD. A set of linker-insertion and deletion mutants
      of HSV type 1 (HSV-1) gD was analyzed for effects of the mutations on binding of
      gD to HVEM and nectin-1, on viral glycoprotein-induced cell fusion with target
      cells expressing HVEM or nectin-1 and on complementation of infectivity of a gD
      null HSV-1 viral mutant. Insertions after amino acid 151 or 225 or deletion of
      amino acids 234-244 disrupted (i) binding of the mutant forms of gD to both
      receptors and (ii) functional interactions (cell fusion and complementation) with
      both receptors, but were without effect on cell surface expression. Insertions in
      the N-terminal domain of gD (after amino acid 12, 34 or 43) disrupted binding to
      HVEM and functional activities with HVEM, as expected from a previously reported
      X-ray structure of a gD-HVEM complex, but were without effect in the case of
      nectin-1. These and other results indicate that the mutations disruptive of
      interactions with both receptors probably affect conformations of contact sites
      that are different for each receptor.

PMID- 14972558
TI  - PDZ domain-binding motif of human T-cell leukemia virus type 1 Tax oncoprotein
      augments the transforming activity in a rat fibroblast cell line.
AB  - While human T-cell leukemia virus type 1 (HTLV-1) is associated with the
      development of adult T-cell leukemia (ATL), HTLV-2 has not been reported to be
      associated with such malignant leukemias. HTLV-1 Tax1 oncoprotein transforms a
      rat fibroblast cell line (Rat-1) to form multiple large colonies in soft agar,
      and this activity is much greater than that of HTLV-2 Tax2. We have demonstrated
      here that the increased number of transformed colonies induced by Tax1 relative
      to Tax2 was mediated by a PDZ domain-binding motif (PBM) in Tax1, which is absent
      in Tax2. Tax1 PBM mediated the interaction of Tax1 with the discs large (Dlg)
      tumor suppressor containing PDZ domains, and the interaction correlated well with
      the transforming activities of Tax1 and the mutants. Through this interaction,
      Tax1 altered the subcellular localization of Dlg from the detergent-soluble to
      the detergent-insoluble fraction in a fibroblast cell line as well as in HTLV-1
      infected T-cell lines. These results suggest that the interaction of Tax1 with
      PDZ domain protein(s) is critically involved in the transforming activity of
      Tax1, the activity of which may be a crucial factor in malignant transformation
      of HTLV-1-infected cells in vivo.

PMID- 14972559
TI  - The human immunodeficiency virus Vpr protein binds Cdc25C: implications for G2
      arrest.
AB  - The human immunodeficiency virus (HIV) encodes a gene product, Vpr, which causes
      infected cells to arrest or delay in the G2 phase of the cell cycle. The arrest
      in G2 is characterized by low levels of Cyclin B1-p34Cdc2 activity and
      corresponding inhibitory phosphorylation of p34Cdc2. We find that Vpr directly
      inhibits the in vitro activity of a phosphatase, Cdc25C, which normally activates
      Cyclin B1-p34Cdc2. Vpr binds to Cdc25C both in vitro and in mammalian cells. Vpr
      is also able to inhibit Cdc25C phosphatase activity in vitro although it binds to
      a site on Cdc25C that is distinct from the catalytic site of the enzyme.
      Expression of both a catalytically active mutant of Cdc25C that has reduced
      binding to Vpr as well as a catalytically inactive mutant of Cdc25C that retains
      binding to Vpr is able to largely overcome Vpr-mediated G2 arrest. Finally,
      depletion of Cdc25C from cells also renders them partially resistant to the
      effects of Vpr.

PMID- 14972560
TI  - The vif gene of maedi-visna virus is essential for infectivity in vivo and in
      vitro.
AB  - We have investigated the role of vif in maedi-visna virus (MVV), a lentivirus of
      sheep, by studying in vitro replication of vif-deleted MVV in several cell types,
      and the effects of vif deletion on in vivo infection. By measuring RT activity,
      we found that in comparison to wild-type MVV, growth of vif-deleted MVV was
      similar in fetal ovine synovial (FOS) cells, highly attenuated in sheep choroid
      plexus (SCP) cells, and not detectable in macrophages, natural target cells of
      MVV. Productive infection by vif-deleted MVV could not be demonstrated in sheep.
      An increased mutation frequency was observed in DNA produced by endogenous
      reverse transcription of viral RNA in vif-deleted virions, indicating the
      existence of a factor comparable in action to human APOBEC3G. These results
      suggest that the vif gene of MVV is essential for infectivity and that the Vif
      protein protects the viral genome from enpackaged mutagenic activities.

PMID- 14972561
TI  - Efficient replication of full-length murine leukemia viruses modified at the
      dimer initiation site regions.
AB  - Retroviruses encapsidate two copies of full-length viral RNA molecules linked
      together as a dimeric genome. RNA stem loop structures harboring palindromic (or
      "kissing") loop sequences constitute important cis-elements for viral
      dimerization known as dimer initiation sites (DIS). In murine leukemia virus
      (MLV), a 10-mer and a 16-mer palindrome (DIS-1 and DIS-2, respectively) located
      in the viral leader region mediate dimerization in vitro and affect dimer
      stability of vector RNA in vivo. We have investigated the effect on viral
      replication of introducing deletions or nucleotide substitutions within these
      palindromes in a full-length MLV genome. Our results demonstrate that viruses
      modified at the dimer initiation site regions are viable and show wild-type
      levels of RNA encapsidation. One mutant lacking the DIS-1 palindrome was severely
      impaired and displayed an increased cellular ratio of spliced versus genomic RNA
      that most likely contributes to the inefficient replication. The implications for
      development of DIS-modified retrovirus-based vectors are discussed.

PMID- 14972562
TI  - Amino acid residues Tyr-67, Asn-72, and Asp-73 of the TVB receptor are important
      for subgroup E avian sarcoma and leukosis virus interaction.
AB  - The chicken TVB(S1) protein serves as the cellular receptor for the cytopathic
      subgroups B and D avian sarcoma and leukosis viruses (ASLVs) as well as for the
      non-cytopathic subgroup E ASLV. Previous studies had mapped the subgroup B viral
      interaction determinants to a region that was located between residues 32 and 46
      of TVB(S1) [J. Virol. 76 (2002) 5404]. To gain a greater insight into ASLV Env
      receptor interactions and the possible role of these interactions in viral
      cytopathic effects, we employed a homolog-scanning mutagenesis approach to
      identify amino acid residues important for subgroup E viral receptor function by
      exchanging amino acid residues between TVB(S1) and its human homolog, DR5. These
      studies identified residues Tyr-67, Asn-72, and Asp-73 of TVB(S1) as important
      subgroup E viral interaction determinants. Intriguingly, these three residues are
      conserved between TVB(S1) and DR5, demonstrating that the human protein contains
      critical subgroup E viral interaction determinants, but in this context, they
      cannot support viral entry. These data confirm that the molecular determinants of
      the TVB receptor required for subgroup E viral entry are completely distinct from
      those used by subgroup B viruses.

PMID- 14972563
TI  - Differential regulation of innate and adaptive immune responses in viral
      encephalitis.
AB  - Viral encephalitis is a global health concern. The ability of a virus to modulate
      the immune response can have a pivotal effect on the course of disease and the
      fate of the infected host. In this study, we sought to understand the
      immunological basis for the fatal encephalitis following infection with the
      murine coronavirus, mouse hepatitis virus (MHV)-JHM, in contrast with the more
      attenuated MHV-A59. Distinct glial cell cytokine and chemokine response patterns
      were observed within 3 days after infection, became progressively more polarized
      during the course of infection and with the infiltration of leukocytes. In the
      brain, MHV-JHM infection induced strong accumulation of IFNbeta mRNA relative to
      IFNgamma mRNA. This trend was reversed in MHV-A59 infection and was accompanied
      by increased CD8 T cell infiltration into brain compared to MHV-JHM infection.
      Increased apoptosis appeared to contribute to the diminished presence of CD8 T
      cells in MHV-JHM-infected brain with the consequence of a lower potential for
      IFNgamma production and antiviral activity. MHV-JHM infection also induced
      sustained mRNA accumulation of the innate immune response products interleukin
      (IL)-6 and IL-1. Furthermore, high levels of macrophage-inflammatory protein
      (MIP)-1alpha, MIP-1beta, and MIP-2 mRNA were observed at the onset of MHV-JHM
      infection and correlated with a marked elevation in the number of macrophages in
      the brain on day 7 compared to MHV-A59 infection. These observations indicate
      that differences in the severity of viral encephalitis may reflect the
      differential ability of viruses to stimulate innate immune responses within the
      CNS and subsequently the character of infiltrating leukocyte populations.

PMID- 14972564
TI  - Human murine mammary tumour virus-like agents are genetically distinct from
      endogenous retroviruses and are not detectable in breast cancer cell lines or
      biopsies.
AB  - It has been reported that a human murine mammary tumour virus (MMTV)-like virus
      (HMLV), which may be an endogenous human retrovirus (HERV), occurs in the human
      breast cancer cell lines T47D and MCF-7 and, in 38% of human breast cancer
      biopsies. As the aetiology of most breast cancers remains unknown, it is
      important to verify these observations in differing breast cancer populations
      worldwide. Thus, we sought to determine the genetic relationships between HMLVs,
      MMTVs, and HERVs, and to investigate the association between HMLVs and breast
      cancer biopsies from South London, UK. Phylogenetic analyses of the env/pol
      region indicated that HMLVs are indistinct from MMTVs, and that MMTVS/HMLVs
      exhibit only low sequence homologies with HERVs. A search of the human genome
      confirmed that HMLVs are not endogenous. Using MMTV polymerase chain reaction
      (PCR) primers described previously, we amplified DNA from all cell lines except
      MCF-7 and from 7 of 44 (16%) breast cancer biopsies. A restriction fragment
      length polymorphism assay was designed to distinguish between HMLVs and MMTVs,
      and upon analyses, PCR amplicons appeared to be HMLVs. To confirm these findings,
      amplicons from the T47D cell line and from four randomly selected breast cancer
      patients were sequenced. Of 106 DNA sequences obtained, 103 were homologous with
      a short arm of human chromosome (Chr) 3 (3p13), two with Chr 4, and one with Chr
      8. None of the sequences exhibited significant nucleotide homology with MMTVs,
      HMLVs, or with HERVs (all <50%). Thus, we conclude that (i) HMLVs are integral
      members of the MMTV family; (ii) MMTVs/HMLVs are genetically distinct from HERVs;
      (iii) MMTV/HMLV DNA is not present in human breast cancer cell lines or clinical
      biopsies in our locality.

PMID- 14972565
TI  - Inhibition of herpes simplex virus infection by lactoferrin is dependent on
      interference with the virus binding to glycosaminoglycans.
AB  - Previous reports have indicated that lactoferrin inhibits herpes simplex virus
      (HSV) infection during the very early phases of the viral replicative cycle. In
      the present work we investigated the mechanism of the antiviral activity of
      lactoferrin in mutant glycosaminoglycan (GAG)-deficient cells. Bovine lactoferrin
      (BLf) was a strong inhibitor of HSV-1 infection in cells expressing either
      heparan sulfate (HS) or chondroitin sulfate (CS) or both, but was ineffective or
      less efficient in GAG-deficient cells or in cells treated with GAG-degrading
      enzymes. In contrast to wild-type HSV-1, virus mutants devoid of glycoprotein C
      (gC) were significantly less inhibited by lactoferrin in GAG-expressing cells,
      indicating that lactoferrin interfered with the binding of viral gC to cell
      surface HS and/or CS. Finally, we demonstrated that lactoferrin bound directly to
      both HS and CS isolated from surfaces of the studied cells, as well as to
      commercial preparations of GAG chains. The results support the hypothesis that
      the inhibition of HSV-1 infectivity by lactoferrin is dependent on its
      interaction with cell surface GAG chains of HS and CS.

PMID- 14972566
TI  - A protective effect of epidermal powder immunization in a mouse model of equine
      herpesvirus-1 infection.
AB  - To evaluate the protective effect of epidermal powder immunization (EPI) against
      equine herpesvirus-1 (EHV-1) infection, we prepared a powder vaccine in which
      formalin-inactivated virions were embedded in water-soluble, sugar-based
      particles. A PowderJect device was used to immunize mice with the powder vaccine
      via their abdominal skin. We found that twice-immunized mice were protected
      against challenge with the wild-type virus. This protective effect was equivalent
      to or better than that observed in mice immunized with other types of vaccines,
      including a gene gun-mediated DNA vaccine containing the glycoprotein D (gD) gene
      or conventional inactivated virus vaccines introduced via intramuscular or
      intranasal injections. These findings indicate that the powder vaccine is a
      promising approach for the immunological control of EHV-1 infection, either alone
      or as a part of prime-boost vaccination strategies.

PMID- 14972567
TI  - DNA immunization with a herpes simplex virus 2 bacterial artificial chromosome.
AB  - Construction of a herpes simplex virus 2 (HSV-2) bacterial artificial chromosome
      (BAC) is described. BAC vector sequences were inserted into the thymidine kinase
      gene of HSV-2 by homologous recombination. DNA from cells infected with the
      resulting recombinant virus was transformed into E. coli, and colonies containing
      the HSV-2 BAC (HSV2-BAC) were isolated and analyzed for the expected genotype.
      HSV2-BAC DNA was infectious when transfected back into mammalian cells and the
      resulting virus was thymidine kinase negative. When used to immunize mice, the
      HSV2-BAC DNA elicited a strong HSV-2 specific antibody response that was equal to
      or greater than live virus immunization. Further, HSV2-BAC immunization was
      protective when animals were challenged with a lethal dose of virus. The utility
      of the HSV2-BAC for construction of recombinant virus genomes was demonstrated by
      elimination of the HSV-2 glycoprotein D (gD) gene. A recombinant HSV-2 BAC with
      the gD gene deleted was isolated and shown to be incapable of producing
      infectious virus following transfection unless an HSV gD gene was expressed in a
      complementing cell line. Immunization of mice with the HSV2 gD-BAC also elicited
      an HSV-2 specific antibody response and was protective. The results demonstrate
      the feasibility of DNA immunization with HSV-2 bacterial artificial chromosomes
      for replicating and nonreplicating candidate HSV-2 vaccines, as well as the
      utility of BAC technology for construction and maintenance of novel HSV-2
      vaccines. The results further suggest that such technology will be a powerful
      tool for dissecting the immune response to HSV-2.

PMID- 14972568
TI  - Polyprotein processing: cis and trans proteolytic activities of Sesbania mosaic
      virus serine protease.
AB  - Sesbania mosaic virus (SeMV) polyprotein was shown to undergo proteolytic
      processing when expressed in E. coli. Mutational analysis of the proposed
      catalytic triad residues (H181, D216, and S284) present in the N-terminal serine
      protease domain of the polyprotein showed that the protease was indeed
      responsible for this processing. Analysis of the cleavage site mutants confirmed
      the cleavage between protease-viral protein genome linked (VPg) and VPg-RNA
      dependent RNA polymerase (RdRP) at E(325)-T(326) and E(402)-T(403) sites,
      respectively. An additional suboptimal cleavage at E(498)-S(499) site was also
      identified which resulted in the further processing of RdRP to 10- and 52-kDa
      proteins. Thus, the protease has both E-T and E-S specificities. The polyprotein
      has a domain arrangement of protease-VPg-p10-RdRP, which is cleaved by the
      protease. The purified serine protease was also active in trans and cleaved the
      polyprotein at the same specific sites. These results demonstrate that the serine
      protease domain is responsible for the processing of SeMV polyprotein both in cis
      and in trans.

PMID- 14972569
TI  - The L polymerase protein of parainfluenza virus 3 forms an oligomer and can
      interact with the heterologous Sendai virus L, P and C proteins.
AB  - We recently showed that the L protein of Sendai virus is present as an oligomer
      in the active P-L polymerase complex [Smallwood et al., Virology 304 (2002) 235].
      We now demonstrate using two different epitope tags that the L protein of a
      second respirovirus, human parainfluenza type 3 virus (PIV3), also forms an L-L
      complex. L oligomerization requires the coexpression of the differentially
      epitope tagged L proteins. By exploiting a series of C-terminal truncations the L
      L binding site maps to the N-terminal half of L. There is some complex formation
      between the heterologous PIV3 and Sendai L and P proteins; however, the
      heterologous L protein does not function in transcription of either the PIV3 or
      Sendai template. The PIV3 C protein binds PIV3 L and inhibits RNA synthesis in
      vitro and in vivo. Significant homology exists between the C proteins of PIV3 and
      Sendai and complex formation occurs between the PIV3 and Sendai heterologous C
      and L proteins. In addition, the heterologous C proteins can inhibit
      transcription at approximately 50% of the level of the homologous protein. These
      data suggest that while the C proteins may be functionally somewhat
      interchangeable, the L and P proteins are specific for each virus.

PMID- 14972570
TI  - Variability and genetic structure of the population of watermelon mosaic virus
      infecting melon in Spain.
AB  - The genetic structure of the population of Watermelon mosaic virus (WMV) in Spain
      was analysed by the biological and molecular characterisation of isolates sampled
      from its main host plant, melon. The population was a highly homogeneous one,
      built of a single pathotype, and comprising isolates closely related genetically.
      There was indication of temporal replacement of genotypes, but not of spatial
      structure of the population. Analyses of nucleotide sequences in three genomic
      regions, that is, in the cistrons for the P1, cylindrical inclusion (CI) and
      capsid (CP) proteins, showed lower similar values of nucleotide diversity for the
      P1 than for the CI or CP cistrons. The CI protein and the CP were under tighter
      evolutionary constraints than the P1 protein. Also, for the CI and CP cistrons,
      but not for the P1 cistron, two groups of sequences, defining two genetic
      strains, were apparent. Thus, different genomic regions of WMV show different
      evolutionary dynamics. Interestingly, for the CI and CP cistrons, sequences were
      clustered into two regions of the sequence space, defining the two strains above,
      and no intermediary sequences were identified. Recombinant isolates were found,
      accounting for at least 7% of the population. These recombinants presented two
      interesting features: (i) crossover points were detected between the analysed
      regions in the CI and CP cistrons, but not between those in the P1 and CI
      cistrons, (ii) crossover points were not observed within the analysed coding
      regions for the P1, CI or CP proteins. This indicates strong selection against
      isolates with recombinant proteins, even when originated from closely related
      strains. Hence, data indicate that genotypes of WMV, generated by mutation or
      recombination, outside of acceptable, discrete, regions in the evolutionary
      space, are eliminated from the virus population by negative selection.

PMID- 14972571
TI  - Turning the tides--33 years of Professor Brian Morton.

PMID- 14972572
TI  - Implementation of the European water framework directive from the Basque country
      (northern Spain): a methodological approach.
AB  - The European Water Framework Directive provides a challenge in the development of
      new and accurate methodologies. It addresses assessment of Ecological Quality
      Status within European rivers, lakes, groundwaters, estuaries and coasts.
      Although this directive is simple and flexible in its concept, it is necessary to
      develop an approach based upon scientific knowledge; however, at the same time it
      should be as simple as possible, in order to achieve both requirements and
      comparability of results throughout European waters. This contribution presents
      the first methodological approach to the problem, as used for estuaries and
      coasts of the Basque Country (northern Spain), in: selecting typologies and
      reference conditions; determining biological quality and ecological status; and
      identifying some problems in implementing the WFD. As such, the present paper
      could serve as the basis for a discussion document for other regions and
      countries, throughout Europe.

PMID- 14972573
TI  - Remote sensing of coral reefs and their physical environment.
AB  - There has been a vast improvement in access to remotely sensed data in just a few
      recent years. This revolution of information is the result of heavy investment in
      new technology by governments and industry, rapid developments in computing power
      and storage, and easy dissemination of data over the internet. Today, remotely
      sensed data are available to virtually anyone with a desktop computer. Here, we
      review the status of one of the most popular areas of marine remote sensing
      research: coral reefs. Previous reviews have focused on the ability of remote
      sensing to map the structure and habitat composition of coral reefs, but have
      neglected to consider the physical environment in which reefs occur. We provide a
      holistic review of what can, might, and cannot be mapped using remote sensing at
      this time. We cover aspects of reef structure and health but also discuss the
      diversity of physical environmental data such as temperature, winds, solar
      radiation and water quality. There have been numerous recent advances in the
      remote sensing of reefs and we hope that this paper enhances awareness of the
      diverse data sources available, and helps practitioners identify realistic
      objectives for remote sensing in coral reef areas.

PMID- 14972574
TI  - Dynamic behaviour of polycyclic aromatic hydrocarbons in Brighton marina, UK.
AB  - The distribution of polycyclic aromatic hydrocarbons (PAHs) between various
      phases is fundamental in the control of their movement and impact in the marine
      environment. In this study samples of water and sediments were regularly
      collected from Brighton marina, UK, to quantify the intensity, spatial and
      temporal variations of PAH contamination. The results show clearly that PAH
      behaviour in marine systems is highly complex, and controlled by the interplay of
      PAH sources, compound physicochemical properties, water and sediment movement,
      and field conditions. Levels of total PAHs (16 compounds) in the dissolved phase
      were found to vary between <2 and 11,400 ng/l, with higher values observed in the
      winter months. Total PAH concentration in sediment samples varied between 24 and
      4710 ng/g dry weight. PAHs in water were dominated by low molecular mass
      compounds (2-ring), while PAHs in sediments were mainly derived from 2-4 ring
      compounds. In addition, dissolved concentrations were increased during sediment
      dredging and after a period of severe rainfall. PAHs in Brighton marina are
      likely to be from both pyrolytic and petrogenic sources; as a result, field
      derived distribution coefficients for individual PAHs between sediment and water
      tend to follow the equilibrium partition models, although slight exceedance is
      apparent. The extended partition model incorporating soot carbon has achieved
      limited success in better predicting PAH behaviour.

PMID- 14972575
TI  - The role of burrowing beds and burrows of the SW Atlantic intertidal crab
      Chasmagnathus granulata in trapping organochlorine pesticides.
AB  - The effect of crab beds and bioturbation activity of the SW Atlantic intertidal
      crab Chasmagnathus granulata on the organochlorine pesticide (OCP) concentrations
      in Bahia Blanca estuary, Argentina were studied. Total OCP concentration was
      significantly lower inside than outside the crab burrows. Nevertheless, the
      concentrations from outside the crab beds were lower than from outside crab
      burrows, which indicated that crab beds act as sinks of sediment-bound OCP due to
      the bioturbation activities of the crabs. The same distribution patterns were
      found in all sediments as well as in crabs, being cyclodienes>HCHs>DDTs, although
      large amounts of metabolites rather than the respective parental were found in
      the organism showing the capacity of C. granulata for metabolising parental
      compounds. These more water-soluble compounds are excreted by the faeces and
      finally removed by tidal flushing to the sea. Our results suggest that crabs when
      present play a role in the distribution of sediment-bound OCP and the crab beds
      are modifiers of the dynamic of organic pollutants in estuarine areas.

PMID- 14972576
TI  - Coral cover and partial mortality on anthropogenically impacted coral reefs at
      Eilat, northern Red Sea.
AB  - A photographic analysis was conducted at five shallow reef sites (5-6 m) at Eilat
      (northern Red Sea) to study changes in live coral cover during a 2-year period.
      Logit regression analysis showed that levels of total oxidized nitrogen (TON;
      NO(2)+NO(3)) and the presence of SCUBA divers were significant explicative
      variables of coral partial mortality, while sedimentation rate was not
      significant. Sites exposed to mean TON levels above 0.4 microM TON showed
      significantly lower live stony coral cover and abundance per m(2), and higher
      partial mortality of coral colonies than sites exposed to lower TON. These
      findings may be useful in establishing limits for TON levels at Eilat, but must
      be interpreted with caution due to the complexity of nutrient dynamics in coral
      reefs, the uncertainty of the effects of nutrients on coral physiological
      processes, and the possibility of interactions among multiple coral stressors.

PMID- 14972577
TI  - Evaluation of a Florida coastal golf complex as a local and watershed source of
      bioavailable contaminants.
AB  - Contaminant fate in coastal areas impacted by golf course runoff is not well
      understood. This report summarizes trace metal, pesticide and PCB residues for
      colonized periphyton, Ruppia maritima (widgeon grass), Callinectes sapidus
      Rathbun (blue crabs) and Crassostrea virginica Gemlin (Eastern oyster) collected
      from areas adjacent to a Florida golf course complex which receive runoff
      containing reclaimed municipal wastewater. Concentrations of 19 chlorinated
      pesticides and 18 PCB congeners were usually below detection in the biota. In
      contrast, 8 trace metals were commonly detected although concentrations were not
      usually significantly different for biota collected from reference and non
      reference coastal areas. Residue concentrations in decreasing order were
      typically: zinc, arsenic, copper, chromium, lead, nickel, cadmium and mercury.
      Mean BCF values for the eight trace metals ranged between 160-57000 (periphyton),
      79-11033 (R. maritima), 87-162625 (C. virginica) and 12-9800 (C. sapidus). Most
      trace metal residues in periphyton colonized adjacent to the golf complex, were
      either similar to or significantly less than those reported for periphyton
      colonized in nearby coastal areas impacted by urban stormwater runoff and treated
      municipal and industrial wastewater discharges. Consequently, the recreational
      complex does not appear to be a major source of bioavailable contaminants locally
      nor in the immediate watershed based on results for the selected biota.

PMID- 14972578
TI  - Persistent organic pollutants and histological lesions in Mayan catfish Ariopsis
      assimilis from the Bay of Chetumal, Mexico.
AB  - Livers of catfish (Ariopsis assimilis) from the Bay of Chetumal were analyzed for
      organochlorine compounds and hydrocarbons as part of a study to diagnose the
      environmental health of the Bay after a catfish mass mortality that occurred in
      1996. The presence of histological lesions in several organs of the fish as
      result of chemical exposure was also evaluated. The concentrations of organic
      pollutants found in the Bay may be considered high if compared to the levels
      reported for sites affected by chemical pollution. High prevalences of cellular
      alteration histopathologies were found in liver, including hepatic tumors. The
      presence of some lesions may be related statistically to environmental pollution
      in the Bay, specially with chlorinated compounds.

PMID- 14972579
TI  - Impacts of dredged material disposal on a tropical soft-bottom benthic
      assemblage.
AB  - The soft-bottom benthic macrofauna in a spoil-ground of dredged material in
      Cleveland Bay, North Queensland, Australia, was studied to detect possible
      impacts of the disposal of sediments. The spatial distribution of the assemblage
      was studied in relation to the source of the impact at 28 stations on four
      occasions during 1998 and 1999. Additionally, environmental variables were
      measured on each occasion at each station. Macrobenthic assemblages inside the
      spoil-ground were different from assemblages outside the spoil ground only
      immediately after (15 days) the disposal of dredged material. Given the decrease
      in the abundance of organisms and number of species, it is suggested that this
      effect was due to direct burial of the macrobenthic assemblage inside the spoil
      ground. Macrobenthic assemblages inside the spoil ground were not different from
      assemblages outside the spoil ground 3 months after dumping. These results
      suggest that the soft-bottom macrobenthic assemblages may respond quickly to the
      disturbance associated with the dumping of dredged material.

PMID- 14972580
TI  - Metal contents in Porites corals: Anthropogenic input of river run-off into a
      coral reef from an urbanized area, Okinawa.
AB  - In order to monitor pollutants from urban areas to coral reefs, metal contents in
      Porites coral samples collected from the Hija River mouth and at nearby sites
      from the estuary were analyzed. The corals were cleaned by oxidative and
      reductive treatments to effectively eliminate detritus and organic materials.
      Metal-to-calcium (Me/Ca) ratios in the samples were determined by ICP-MS.
      Filtered samples of river water were also measured similarly for metal
      concentrations. The extent of anthropogenic contribution by riverine input was
      assessed by comparing the Me/Ca values in corals to those of Rukan-sho, an
      unpolluted coral reef. High riverine inputs of Mn, Cd, Zn and Ag were observed
      from Me/Ca values in the coral samples. Manganese in the coral samples showed
      strong dependence on salinity, varying inversely to the distance from terrestrial
      sources. Considering a lead background of 25.0 nmol/mol measured in the Rukan-sho
      corals, Pb/Ca in corals of the Hija River estuary that are two and three times
      higher may indicate lead enrichment in the river mouth. Because Pb is only
      moderately high in the Hija River water compared to its concentration in surface
      seawater, lead may have accumulated in the estuarine water and sediments,
      resulting in an elevated concentration of lead available for coral uptake.

PMID- 14972581
TI  - Increasing levels and biomagnification of persistent organic pollutants (POPs) in
      Antarctic biota.
AB  - Representatives of the Antarctic food web (krill, cephalopod, fish, penguin,
      seal) of the area around Elephant Island and from the Weddell Sea were analysed
      for the most recalcitrant organochlorine compounds. Due to sorption of the
      compounds to sinking particles and accumulation in sediments, two benthic fish
      species (Gobionotothen gibberifrons, Chaenocephalus aceratus) feeding on benthos
      invertebrates and fish reflected significantly increasing concentrations within a
      decade (1987-1996), while a benthopelagic species (Champsocephalus gunnari)
      feeding on krill did not. In the pelagic food chain, lipid normalised
      concentrations of all compounds increased from Antarctic krill to fish proving
      that biomagnification of highly lipophilic pollutants (log octanol-water
      partition coefficient>5) occurs in water-breathing animals. As top predators
      Weddell and southern elephant seals (Leptonychotes weddellii, Mirounga leonina)
      biomagnified the persistent organic pollutants relative to krill 30-160 fold with
      the exception of hexachlorobenzene, the levels of which were lower than in fish
      indicating its intense specific elimination.

PMID- 14972582
TI  - Effects of shoreline discharge of iron mine tailings on a marine soft-bottom
      community in northern Chile.
AB  - This study evaluates the magnitude and extension of the impact produced by the
      discharge of inert allochthonous materials, including clays and particulate iron,
      on macrobenthic soft-bottom assemblages in the subtidal zone of a coastal bay in
      north-central Chile. An average of 118 Ton h(-1) of finely divided solids were
      discharged into the rocky intertidal zone of the bay for a period of over 16
      years, producing continuous turbidity in the water column and sedimentation in
      the subtidal zone. Data obtained four months before cessation of the discharge
      showed that the macrofauna present at 20 and 50 m depth in the bay suffered an
      important decrease in abundance and species richness, low diversity/high
      dominance, and deep changes in community structure related to the discharge. The
      faunal assemblages present at 110 m depth did not show effects from the
      discharge, suggesting that the impact was limited to the inner part of the bay.
      The impoverished faunal aggregates at 20 and 50 m depth showed exclusive
      domination by the Lumbrineris bifilaris (polychaete)-Diastylis tongoyensis
      (cumacean) association, representing a simple trophic guild of deposit feeders.
      The complete absence of opportunistic species such as capitellid, spionid, and/or
      cirratulid polychaetes may be associated with the turbidity and sedimentation
      levels in the bay.

PMID- 14972583
TI  - Transport of mecoprop from agricultural soils to an adjacent salt marsh.
AB  - Salt marshes are important ecological areas and play a significant role in
      coastal flood defence schemes. In many areas of the UK they are adjacent to
      agricultural areas utilised for the growth of cereal crops, for which mecoprop is
      used as a selective herbicide in the control of broad-leaf weeds. This study
      measured concentrations of mecoprop in soils, drainage ditch waters and sediments
      and salt marsh sediments over a period of 138 days following spring application.
      Soil concentrations of up to 1827 microg/g were recorded after application, which
      demonstrated a half life for mecoprop of from 9 to 12 days, with first order
      kinetics. However, a major rainfall event 9 days after application resulted in
      significant transport of herbicide to the salt marsh via subsurface field drains,
      drainage ditches and discharge sluice. Mecoprop concentrations of up to 386
      microg/l observed in water samples were above UK guidelines.

PMID- 14972584
TI  - The influence of the Po River discharge on phytoplankton bloom dynamics along the
      coastline of Pesaro (Italy) in the Adriatic Sea.
AB  - In recent years, eutrophic phenomena have frequently been reported in the Italian
      coastal waters of the northern Adriatic Sea. The aim of the present study was to
      determine that the phytoplankton blooms occurring along the Italian coastline in
      the area of Pesaro are caused by the Po River waters. In fact between October and
      December 2000 the nutrient load flushed into the sea from local rivers is not
      significant (phosphorus 10 tons and nitrogen 110 tons), instead N and P load from
      the Po River are: 650 and 8969 tons. The bloom episodes occurred during this
      period, at which time hypoxia developed on the sea bottom. The phytoplankton cell
      concentrations were 40.0 x 10(6) cells L(-1), and a significant presence of
      diatoms was observed. This issue is important in analysing the anthropogenic
      disturbances and environmental changes. The eutrophic seawater conditions were
      also analysed using the eutrophic index.

PMID- 14972585
TI  - Comparing bleaching and mortality responses of hard corals between southern Kenya
      and the Great Barrier Reef, Australia.
AB  - We compared the bleaching and mortality response (BMI) of 19 common scleractinian
      corals to an anomalous warm-water event in 1998 to determine the degree of
      variation between depths, sites, and regions. Mombasa corals experienced a
      greater temperature anomaly than those on the Great Barrier Reef (GBR) sites and
      this was reflected in the greater BMI response of most taxa. Comparing coral taxa
      in different sites at the same depth produced high correlation coefficients in
      the bleaching response in Kenya at 2 m (r=0.86) and GBR at 6 m depth sites
      (r=0.80) but less in the GBR for shallow 2 m sites (r=0.49). The pattern of taxa
      susceptibility was remarkably consistent between the regions. Coral taxa
      explained 52% of the variation in the response of colonies to bleaching between
      these two regions (Kenya BMI=0.90 GBR BMI+26; F(1,19) - 18.3; p < 0.001; r2 =
      0.52). Stylophora and Pocillopora were consistently susceptible while Cyphastrea,
      Goniopora Galaxea and Pavona were resistant in both regions. Three taxa behaved
      differently between the two regions; Acropora, and branching Porites were both
      moderately affected on the GBR but were highly affected in Kenya while the
      opposite was true for Pavona. These results suggest that a colonies response to
      bleaching is phylogenetically constrained, emphasizing the importance of features
      of the host's physiology or morphology in determining the response to thermal
      stress.

PMID- 14972586
TI  - Whole-bird models for the magnetic cleansing of oiled feathers.
AB  - Iron powder, a promising dry-cleansing agent for oiled feathers where both the
      contaminant and the cleansing agent may be harvested magnetically, has been
      tested on the plumage of whole-bird models. The breast and back plumage of
      Mallard Duck (Anas platyrhynchos) and Little Penguin (Eudyptula minor) carcasses
      were patch-contaminated with commercial-grade engine oil, three different crude
      oils, and an oil/seawater emulsion. The plumage was then subjected to a magnetic
      cleansing protocol. The contaminant removal was assessed gravimetrically and was
      found to reflect the outcomes for a previously reported in vitro study using
      feather clusters. Between 92-98% of the contaminants, and effectively all of the
      cleansing agent, were removed from the feathers.

PMID- 14972587
TI  - Inhomogeneous distribution of polycyclic aromatic hydrocarbons in different size
      and density fractions of contaminated sediment from Auckland Harbour, New
      Zealand: an opportunity for mitigation.
AB  - Polycyclic aromatic hydrocarbons (PAHs) in sediment from Auckland Harbour (New
      Zealand) are not distributed evenly throughout bulk sediment, but highly
      concentrated in coarser, low-density fractions. Concentrations of 24 PAHs,
      measured in sediment that was separated into six size fractions that were
      furthermore separated into two density sub-fractions by flotation in sodium
      polytungstate solution (rho = 2.15 g cm(-3)), varied between 4-103 microg g(-1)dw
      among grain size fractions and 2-998 microg g(-1)dw for density sub-fractions.
      Highest PAH concentrations were measured in the low density, 125-250 microm
      fraction. All sediment fractions had a similar relative PAH composition,
      dominated by >3-ring PAHs, suggesting a common pyrogenic origin. Low density
      material had 10-200 times higher PAH concentrations and 10-100 times higher
      organic carbon (OC) content, yet differences in OC content only partially
      accounted for variations in PAH concentration. Low density particles contributed
      more than 75% of the Sigma PAH, while comprising only 3% of bulk sediment dry
      weight. This may have significant utility for contaminant mitigation efforts in
      Auckland Harbour.

PMID- 14972588
TI  - The distribution and sources of polycyclic aromatic hydrocarbons in Narragansett
      Bay surface sediments.
AB  - Polycyclic aromatic hydrocarbons (PAHs) were measured in 41 surface sediments
      from Narragansett Bay, RI. All the analytes generally decrease down bay from the
      Seekonk, Providence and Taunton Rivers at the head of the bay. Total PAHs ranged
      from 0.569 to 216 microg/g with 27% exceeding the effects range median (ERM) of
      44.8 microg/g and 73% of the stations exceeding the effects range low (ERL) of
      4.02 microg/g (Long et al., 1995). Based on principal component analysis, the
      major source of the contaminants in Narragansett Bay was the Providence River
      while the coves and Taunton River/Mt. Hope Bay appeared to only have a limited
      influence on the open bay. PAH source ratios indicate that creosote and/or coal
      may be the most significant contributor of pyrogenic high molecular weight PAHs
      in Narragansett Bay, along with significant contributions from diesel exhaust.

PMID- 14972589
TI  - Relationship between soil cellulose decomposition and oil contamination after an
      oil spill at Swanson Creek, Maryland.
AB  - In wetlands, oil spills may affect decomposition in soils, which controls organic
      matter accumulation, the primary contributor to positive elevation change. In
      this study we examined how oil from a spill affected organic matter decomposition
      in soils of a brackish intertidal marsh in Maryland. Decomposition was measured
      using the cellulose (cotton) strip technique. Cellulose decomposition was not
      affected by concentrations of different oil components (total hydrocarbons, total
      resolved hydrocarbons, and polycyclic aromatic hydrocarbons). Rather, other
      abiotic characteristics of the soil had strong effects on decomposition rates,
      including strong negative effects of soil depth and salinity, and a positive
      effect of pH. Measures of soil fertility (NH(4)-N and PO(4)-P) were not
      significantly related to cellulose decomposition. Thus, we conclude that
      decomposition was controlled more by naturally occurring environmental factors
      rather than by exposure to oil.

PMID- 14972590
TI  - Copper emissions from antifouling paint on recreational vessels.
AB  - Trace metals, especially copper, are commonly occurring contaminants in harbors
      and marinas. One source of copper to these environs is copper-based antifouling
      coatings used on vessel hulls. The objective of this study was to measure
      dissolved copper contributions from recreational vessel antifouling coatings for
      both passive leaching and hull cleaning activities. To accomplish this goal,
      three coating formulations, including hard vinyl, modified epoxy and a biocide
      free bottom paint were applied on fiberglass panels and placed in a harbor
      environment. In situ measurements of passive leaching were made using a
      recirculating dome system. Monthly average flux rates of dissolved copper for the
      hard vinyl and modified epoxy coatings were 3.7 and 4.3 microg/cm(2)/day,
      respectively, while flux rates for the biocide free coating was 0.2
      microg/cm(2)/day. The highest passive flux rates were measured initially after
      cleaning activities, rapidly decreasing to a baseline rate within three days,
      regardless of copper-based coating formulation. Hull cleaning activities
      generated between 8.6 and 3.8 microg dissolved copper/cm(2)/event for the
      modified epoxy and hard vinyl coatings, respectively. Aggressive cleaning using
      an abrasive product doubled the copper emissions from the modified epoxy coating,
      but produced virtually no change in the much tougher hard vinyl coating. When
      compared on a mass basis, roughly 95% of copper is emitted during passive
      leaching compared to hull cleaning activities over a monthly time period for a
      typical 9.1 m power boat.

PMID- 14972591
TI  - Trace metals and nutrients in bottom sediments of the Southport Broadwater,
      Australia.

PMID- 14972592
TI  - Trace metal distribution in the mussel Perna perna along the Moroccan coast.

PMID- 14972593
TI  - Trace element residues in eggs of Little Egret (Egretta garzetta) and Black
      crowned Night Heron (Nycticorax nycticorax) from Hong Kong, China.

PMID- 14972594
TI  - Comparative paralytic shellfish toxin profiles in two marine bivalves during
      outbreaks of Gymnodinium catenatum (Dinophyceae) in the Gulf of California.

PMID- 14972595
TI  - Bentix Index vs. Biotic index in monitoring: an answer to Borja et al., 2003.

PMID- 14972597
TI  - What are theories for? Concept use throughout the continuum of dinosaur
      expertise.
AB  - Although it is now well established that object concepts are situated within
      broader systems of theoretical knowledge, it is less clear how theories influence
      the use of object concepts at various points throughout the continuum of
      expertise. Two studies were conducted to investigate the impact of specific
      theories (concerning dinosaurs) and overarching framework theories (of biology)
      on children's and adults' performance on categorization tasks involving familiar
      and less familiar concepts. Although expertise increased the quantity of deep
      feature knowledge possessed by children and increased their understanding of
      biologically adaptive relations among features, few aspects of children's
      performance generalized beyond highly familiar dinosaurs. Children's specific
      theories related to dinosaurs were empirically constrained and relatively
      dissociated from other types of biological knowledge. The interaction of specific
      concept knowledge with broader framework theories of biology throughout the
      continuum of expertise is considered.

PMID- 14972598
TI  - Developmental trends in simple and selective inhibition of compatible and
      incompatible responses.
AB  - This study examined age-related change in the ability to inhibit responses using
      two varieties of the stop signal paradigm. Three age groups (29 7-year-olds, 24
      10-year-olds, and 28 young adults) performed first on a visual choice reaction
      task in which the spatial mapping between the go signal and response was varied
      between blocks. The choice task was then complicated by randomly inserting a
      visual stop signal on 30% of the trials. In the simple stop signal paradigm, the
      stop signal required the inhibition of the planned response. In the selective
      stop signal paradigm, the stop signal required response inhibition only when the
      stop signal was presented at the same side as the instructed response to the go
      signal. The results showed that simple stopping was faster than selective
      stopping and that selective, but not simple, stopping of incompatible responses
      was slower than stopping of compatible responses. Brinley plot analysis yielded
      linear functions relating children's latencies to adults' latencies. Analysis of
      shared variance indicated that developmental change in the speed of selective
      stopping continued to be significant even when the effect associated with simple
      stopping was removed. This pattern of findings is discussed vis-a-vis notions of
      global versus specific developmental trends in the speed of information
      processing.

PMID- 14972599
TI  - But I thought it was Mickey Mouse: the effects of new postevent information on 18
      month-olds' memory.
AB  - Two experiments examined the effects of postevent information on 18-month-olds'
      event memory. Experiment 1 (N=60) explored whether children's memory was
      reinstated when action information was eliminated from the reinstatement and only
      object information was introduced. Experiment 2 (N=48) examined children's recall
      when either (a). information about the objects' target actions was replaced with
      new action information or (b). the original training objects were replaced with
      new objects. In an elicited-imitation paradigm, children were trained to perform
      six target actions, watched a video reinstatement 10 weeks later, and were tested
      for recall 24 h after reinstatement. Two results were found. First, a video
      reminder eliminating action information reinstated children's memory as
      effectively as a video containing object and action information. Second, children
      were reminded of their past training when during reinstatement action information
      was preserved and new objects were presented but were not reminded when object
      information was preserved and new actions were presented.

PMID- 14972600
TI  - Inhibition and shifting in children with learning deficits in arithmetic and
      reading.
AB  - The executive functions of inhibition and shifting were studied in arithmetic
      disabled children, reading-disabled children, reading plus arithmetic-disabled
      children, and controls (N = 74). Measures involved the rapid naming of objects,
      digits, letters, or quantities with or without additional task requirements that
      reflected inhibition or shifting. Also, the Making Trails task, reflecting
      shifting, was administered. For tasks without executive demands, arithmetic
      disabled children were slower in the naming of digits and quantities, whereas
      reading-disabled children were slower in the naming of digits and letters. For
      the executive tasks, arithmetic-disabled children as well as reading plus
      arithmetic-disabled children were impaired on the Making Trails task and on an
      object naming task that required both inhibition and shifting. Reading-disabled
      children exhibited no problems in executive functioning. Furthermore, it was
      shown that reading plus arithmetic-disabled children experienced the combination
      of problems that characterize children with a single learning deficit.

PMID- 14972601
TI  - Morphology of synthetic goethite particles.
AB  - The specific surface area of synthetic goethite depends on the preparation: the
      Fe(III):OH ratio, the rate of base titration of Fe salt, and the temperature and
      time of crystallization. The crystals also have different morphologies as
      determined by SEM or TEM. Carbon coating is used to improve the quality of SEM
      images of nonconducting specimens. We show here that needle-like goethite
      particles become substantially thicker in the course of standard carbon coating,
      and the length-to-width ratio obtained for carbon-coated particles is lower than
      that for the original goethite particles. The morphology of the goethite
      particles was also studied by tapping mode AFM.

PMID- 14972602
TI  - Surfactant immobilized interlayer species bonded to montmorillonite as recyclable
      adsorbent for lead ions.
AB  - Removal of lead ( Pb2+ ) ions from aqueous solution by adsorption onto surfactant
      immobilized interlayer species bonded to montmorillonite clay (SIIS-clay) was
      investigated. Surfactant-immobilized interlayer chromate bound to clay (SIICr
      clay) was prepared by treatment of montmorillonite clay with
      hexadecyltrimethylammonium (HDTMA) bromide followed by chromate adsorption at the
      intergallery framework of the clay. Experiments were carried out as a function of
      solution pH, solute concentration, and temperature (5-45 degrees C). The Dubinin
      Kaganer-Radushkevich (DKR) model was adopted to describe the single-solute
      adsorption isotherms. Adsorption energy for lead ions on SIICr-clay computed from
      the DKR equation shows that a precipitation mechanism was operative. The
      thermodynamic parameters ( Delta G 0, Delta H 0, and Delta S 0) for lead ion
      adsorption on SIICr-clay were also determined from the temperature dependence.
      The kinetics of metal ion adsorption was examined and the first-order rate
      constant was finally evaluated. Adsorbed lead ions could be recovered completely
      on leaching with the disodium salt of ethylenediamine tetraacetic acid (EDTA)
      solution and the adsorbent was found to readsorb lead ions repeatedly after
      leaching. Thus, surfactant-modified smectite clays offer an effective method for
      designing a recyclable adsorbent for lead ions.

PMID- 14972603
TI  - Adsorption of bovine serum albumin on nanosized magnetic particles.
AB  - Adsorption of bovine serum albumin (BSA) on nanosized magnetic particles
      (Fe(3)O(4)) was carried out in the presence of carbodiimide. The equilibrium and
      kinetics of the adsorption process were studied. Nanosized magnetic particles
      (Fe(3)O(4)) were prepared by the chemical precipitation method using Fe2+, Fe3+
      salts, and ammonium hydroxide under a nitrogen atmosphere. Characterizations of
      magnetic particles were carried out using transmission electron microscopy (TEM)
      and a vibrating sample magnetometer (VSM). Fourier-transform infrared
      spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) were used to
      confirm the attachment of BSA on magnetic particles. Effects of pH and salt
      concentrations were investigated on the adsorption process. The experimental
      results show that the adsorption of BSA on magnetic particles was affected
      greatly by the pH, while the effect of salt concentrations was insignificant at a
      low concentration range. The adsorption equilibrium isotherm was fitted well by
      the Langmuir model. The maximum adsorption of BSA on magnetic particles occurred
      at the isoelectric point of BSA. Adsorption kinetics was analyzed by a linear
      driving force mass-transfer model. BSA was desorbed from magnetic particles under
      alkaline conditions, which was confirmed by SDS-PAGE electrophoresis and FTIR
      results.

PMID- 14972604
TI  - Film and intraparticle mass transfer during the adsorption of metal ions onto
      bone char.
AB  - The sorption of three metal ions, namely, copper, cadmium, and zinc, onto bone
      char has been studied in terms of equilibrium and rate studies. Equilibrium
      studies have been analyzed using the Langmuir isotherm equation and the maximum
      sorption capacities for the metals were 0.477, 0.709, and 0.505 mmolg(-1) bone
      char for cadmium, copper, and zinc ions, respectively. The kinetic experimental
      data were used to analyze the effect of external film boundary layer and
      intraparticle mass transfer resistance on the sorption process and its
      significance. Four methods of determining the external film transport coefficient
      were developed and tested; three utilized experimental data to obtain the
      coefficient and the fourth method was completely empirical. The three
      experimentally based models give very similar results and consequently similar
      values of the deviation error values, whereas the error values for the empirical
      correlation were greater than these three values. The results also demonstrated
      that the methods for determining the film coefficient could be integrated into
      more complex diffusion-transport models such as film-intraparticle diffusion
      processes.

PMID- 14972605
TI  - Intersection of isotherms for phosphate adsorption on hematite.
AB  - Adsorption isotherms for phosphate on hematite were prepared at pH 3.39, 4.16,
      5.10, 5.63, and 6.71 in this study. It was found that the adsorption isotherms at
      pH 5.63 and 6.71 intersected those at pH 4.16 and 5.10. Using surface
      complexation theory, this study demonstrates that the intersection of adsorption
      isotherms results from (1) phosphate being adsorbed mainly as protonated
      complexes at pH 4.16 and 5.10 but as nonprotonated complexes at pH 5.63 and 6.71;
      (2) the electric potential (psi) at the surface of hematite changing with pH at a
      rate less than 29.5 mV per pH unit (-d psi /dpH approximately equal 8.9 mV/pH).
      Fundamentally, however, it seems that the dominance of an imperfect (001) crystal
      face in the hematite sample is responsible for a low value of -d psi/dpH and the
      intersection of adsorption isotherms. The adsorption behavior may be regarded as
      characteristic behavior of protonation of adsorbed phosphate on an oxide with a
      small value of -d psi / dpH.

PMID- 14972606
TI  - Preparation and characterization of positively charged ruthenium nanoparticles.
AB  - Positively charged ruthenium nanoparticles were prepared by NaBH(4) reduction at
      room temperature and at pH values lower than 4.9. The ruthenium nanoparticles
      were characterized by zeta potential measurement, TEM, XPS, and XRD. Particles
      with a mean diameter of 1.8 nm and a standard deviation of 0.40 nm could be
      obtained under the experimental conditions. The surface charge on the particles
      is believed to originate from hydrated proton adsorption. The positively charged
      ruthenium nanoparticles could be used as the starting material for further
      functionalization by PVP, ethylenediamine, and dodecylamine.

PMID- 14972607
TI  - Increasing the arsenate adsorption capacity of neutralized red mud (Bauxsol).
AB  - The possibility of increasing the arsenate adsorption capacity of seawater
      neutralized red mud (Bauxsol) through acid treatment, combined acid and heat
      treatment, and the addition of ferric sulfate (Fe(2)(SO(4))(3).7H(2)O) or
      aluminum sulfate (Al(2)(SO(4))(3). 18H(2)O) is investigated. The results show
      that acid treatment alone, as well as in combination with heat treatment
      increases the removal efficiency, with the combination providing the best
      removal. Adding ferric sulfate or aluminum sulfate, however, suppress the
      removal. The results also show that activated Bauxsol (AB) produced using
      combined acid and heat treatment can remove roughly 100% arsenate (at pH 4.5)
      with or without competing anions (i.e., phosphate, bicarbonate, and sulfate) when
      the initial arsenate concentration is < or = 2 mgl(-1). Furthermore, it is found
      that the adsorption process using AB is not accompanied by the release of
      unwanted contaminants, and TCLP results indicate that the spent AB is not
      hazardous. It is believed that the AB produced here has good potential as an
      alternative adsorbent to conventional methods for removing arsenate from water.

PMID- 14972608
TI  - Removal of lead and chromium from wastewater using bagasse fly ash--a sugar
      industry waste.
AB  - An inexpensive and effective adsorbent was developed from bagasse fly ash,
      obtained from a sugar industry, for the dynamic uptake of lead and chromium. Lead
      and chromium are sorbed by the developed adsorbent up to 96-98%. The removal of
      these two metal ions up to 95-96% was achieved by column experiments at a flow
      rate of 0.5 mlmin(-1). The adsorption was found to be exothermic in nature. The
      adsorbent was successfully tried for the removal of lead and chromium from
      wastewater in our laboratory. The developed system for the removal of two ions is
      very useful, economic, rapid, and reproducible.

PMID- 14972609
TI  - Temperature and pressure dependence of quercetin-3-O-palmitate interaction with a
      model phospholipid membrane: film balance and scanning probe microscopy study.
AB  - The molecular interaction of quercetin-3-O-palmitate (QP) with
      dimyristoylphosphatidylcholine (DMPC) has been studied. Film balance measurements
      of the average molecular area vs QP molar fraction in DMPC/QP mixed monolayers
      showed that relevant positive deviations from ideality, i.e., a less dense
      monolayer packing, occurred for a temperature of 10 degrees C, below the critical
      melting transition temperature of DMPC monolayers T c m approximately equal 20
      degrees C), while ideal behavior was observed at 37 degrees C, above this phase
      transition temperature. The positive deviation observed at low temperatures in
      the average molecular area increased with the surface pressure. Scanning probe
      microscopy measurements performed on mixed monolayers transferred on mica showed
      that the deviations from ideality were connected to the formation of nanometric
      scale QP-rich domains. However, the formation of aggregates was observed only for
      relatively high-QP molar fractions X QP > or = 0.25 at 10 degrees C, while it was
      not observed at 37 degrees C, i.e., when the ideal mixing was found at the
      air/water interface. The observed effects are explained in terms of a temperature
      and surface pressure-dependent phase-separation process based on the
      predominance at low temperature and low molecular mobility of QP-QP and DMPC-DMPC
      aggregation forces, prompting the formation of QP-rich domains embedded in a DMPC
      rich matrix. High temperature prompts the QP/DMPC ideal mixing.

PMID- 14972610
TI  - Preparation and characterization of biodegradable poly(l-lactide)/poly(ethylene
      glycol) microcapsules containing erythromycin by emulsion solvent evaporation
      technique.
AB  - In this work, the producing of a biodegradable poly(l-lactide)
      (PLA)/poly(ethylene glycol) (PEG) microcapsule by emulsion solvent evaporation
      method was investigated. The effect of PEG segments added to the PLA
      microcapsules on the degradation, size distribution, and release behavior was
      studied. According to the results, PLA/PEG copolymer was more hydrophilic than
      PLA homopolymer, and with lower glass transition temperature. The surface of
      PLA/PEG microcapsules was not as smooth as that of PLA microcapsules, the mean
      diameters of prepared PLA and PLA/PEG microcapsules were 40 and 57 microm,
      respectively. And spherical forms were observed by the image analyzer and the
      scanning electron microscope (SEM). Drug release from microcapsules was affected
      by the properties of PLA/PEG copolymers determined by UV-vis spectra. It was
      found that the drug release rates of the microcapsules were significantly
      increased with adding of PEG, which explained by increasing hydrophilic groups.

PMID- 14972611
TI  - Study of bioadhesion on a flat plate with a yeast/glass model system.
AB  - The attachment of microorganisms to a surface is a critical first step of biofilm
      fouling in membrane processes. The shear-induced detachment of baker's yeast in
      adhesive contact with a plane glass surface was thus experimentally studied,
      using a specially designed shear stress flow chamber. The yeast was marketed
      either as rod-shaped pellets (type I yeast) or as spherical pellets (type II
      yeast). A complete series of experiments for measuring the shear stress necessary
      to detach a given proportion of individual yeast cells of type I or II was
      performed under different environmental conditions (ionic strength, contact
      time). In parallel, the surface physicochemical properties of the cells (surface
      charge, hydrophobicity, and electron donor and electron acceptor components) were
      determined. For the first type of yeast cells, which were rather hydrophilic,
      adhesion to the glass plate was weak. This was due to both electrostatic effects
      and hydrophilic repulsion. Furthermore, adhesion was not sensitive to any
      variation of the ionic strength. For yeast of the second type, adhesion was
      drastically increased. This could be explained by their physicochemical surface
      properties and especially their hydrophobic and electron acceptor components,
      which caused strong attractive van der Waals and Lewis acid-base interactions,
      counterbalancing the electrostatic repulsion. For increasing ionic strengths,
      adhesion was greater, due to lower electrostatic repulsion. The results were
      quantified through the definition of a critical wall shear stress ( tau w 50% )
      required to detach 50% of the yeast cells initially deposited on the glass
      surface. The influence of the contact time was also evaluated and it was shown
      that, whatever the type of yeast, macromolecules such as proteins were released
      into the extracellular medium due to cell lysis and could contribute to the
      formation of a conditioning film. As a result, the cells were more strongly stuck
      to the glass plate.

PMID- 14972612
TI  - The measurement temperature: an important factor relating physicochemical and
      adhesive properties of yeast cells to biomaterials.
AB  - Flow chambers applied to the study of the initial adhesion process of Candida
      parapsilosis are rarely found in the literature. The ability of these
      microorganisms to proliferate and form biofilms in environments at temperatures
      around 22 or 37 degrees C is reflected in the contamination of laboratory
      instruments and material or in human implant infections, respectively. The
      initial interaction between yeasts and substrata is mediated by physicochemical
      forces, which in turn originate from the physicochemical surface properties of
      both interacting phases. In this context, this work aims to relate the initial
      rates of adhesion rates to glass and silicone of Candida parapsilosis, strains
      294 and 289, grown at 22 and 37 degrees C with the theoretical predictions of the
      adhesion process, expressed by the interaction free energies and calculated
      through the physicochemical parameters, which are also measured at 22 and 37
      degrees C. The results indicate that physicochemical parameters of yeasts are
      changed not only by the culture temperature but also by the measurement
      temperature; only when the measurement temperature is equal to the growth
      temperature a coherent relation between in vitro adhesion data and interaction
      free energies can be established. In this sense, the adhesion to glass is
      mediated by long-range forces or, what amounts to the same thing, by Lifshitz-van
      der Waals interaction free energy. On the other hand, the adhesion to silicone
      rubber seems to be moderated by acid-base interaction free energy, which involves
      the presence of short-range forces. Based on these results, it can be assumed
      that the substratum surface properties are directly related to the kind of force
      acting on the initial microbial adhesion process, while cell surface properties
      dictate the changes in the strength of the force between different samples.

PMID- 14972613
TI  - Application of barycentric method for determination of free energy of liquid
      monodisperse system accomplishing diffusion.
AB  - The barycentric method has been applied to determining the thermodynamic
      potential (the free energy) of a liquid rarefied monodisperse colloid system in
      which free unstationary diffusion under constant external conditions has been
      accomplished. Free energy at an arbitrary moment of time has been obtained as a
      function of horizontal mass center shift toward the cuvette cavity geometrical
      center of the liquid disperse system investigated. A very good coincidence
      between the numerical results from the proposed barycentric method and another
      classical thermodynamic method has been observed.

PMID- 14972614
TI  - Preparation of nanometer-sized In2O3 particles by a reverse microemulsion method.
AB  - Nanometer-sized indium oxide (In(2)O(3)) particles have been prepared by chemical
      reaction of inorganic indium compounds and ammonia gas in a reverse microemulsion
      system consisting of water, Triton X-100 (surfactant), n-heptanol (co
      surfactant), and n-octane (oil). Precursor hydroxides precipitated in the
      droplets of water-in-oil (W/O) microemulsion were calcined at different
      temperatures to form indium oxide powder. The factors affecting the particle size
      have been discussed; the calcination temperature is considered to be the
      important factor for controlling the size. In(2)O(3) calcined at 400 degrees C
      had a spherical form and a narrow size distribution. Calcination at 800 degrees C
      led to the formation of particles not only of irregular shape, but also of a wide
      size distribution. With the increase in calcination temperature from 400 to 800
      degrees C, the average size of the particles grew from 7 to about 40 nm. The
      species of reactants used in the aqueous phase had a significant effect on the
      size of the particles. The average diameter of In(2)O(3) particles derived from
      reactant InCl(3) was 7 nm; that of particles derived from In(NO(3))(3) was 15 nm.
      The In(2)O(3) nanoparticles were characterized by transmission electron
      microscopy and X-ray diffraction. The phase behavior of the microemulsions is
      discussed.

PMID- 14972615
TI  - Characterization of fractionated asphaltenes by UV-vis and NMR self-diffusion
      spectroscopy.
AB  - Asphaltenes have been fractionated by liquid/liquid extraction, yielding four
      subfractions. The characteristics of fractionated asphaltenes were studied with
      respect to solubility, aromaticity, heteroatom content, and diffusion behavior.
      It was observed that asphaltenes from the four subfractions showed variations in
      their tendency to flocculate and also distinct differences in aromaticity.
      Furthermore, NMR self-diffusion studies showed that the average diffusion
      coefficients varied for asphaltenes from the different subfractions. The results
      suggest a variation in average size and stability between asphaltenes, depending
      on what subfraction they belong to. The subfraction that consisted of asphaltenes
      with the largest average size and the highest aromaticity was also found to
      contain the asphaltenes that had the strongest tendency to flocculate.

PMID- 14972616
TI  - Formation of platinum nanoparticles at air-water interfaces by the spontaneous
      reduction of subphase chloroplatinate anions by hexadecylaniline Langmuir
      monolayers.
AB  - The one-step electrostatic complexation, reduction of aqueous chloroplatinate
      ions, and capping of the platinum nanoparticles thus formed by hexadecylaniline
      Langmuir monolayers is described. The capping of the platinum nanoparticles
      formed spontaneously at the air-water interface by hexadecylaniline enables their
      facile transfer as multilayers onto suitable solid substrates by the Langmuir
      Blodgett technique. The real-time reduction of the aqueous chloroplatinate ions
      at the air-water interface was followed by measurement of the pressure-area
      isotherms, while the multilayer Langmuir-Blodgett films were characterized by
      quartz crystal microgravimetry, transmission electron microscopy, electron
      diffraction, and X-ray photoemission spectroscopy.

PMID- 14972617
TI  - Small-angle static light scattering of concentrated silica suspensions during in
      situ destabilization.
AB  - The aggregation of concentrated aqueous silica suspensions is characterized by
      means of static light scattering. We use an in situ destabilization mechanism
      based on the enzyme-catalyzed hydrolysis of urea. This method enables us to
      continuously and homogeneously change the interparticle potential from repulsive
      to attractive without disturbing the aggregation process. Moreover, our
      electrostatically stabilized suspensions can be destabilized by two different
      methods. In the first method, the pH is shifted toward the isoelectric point of
      the particles ( Delta pH method), thereby leading to a decrease of their surface
      charge. In the second method, the ionic strength is continuously increased at
      constant pH ( Delta I method), leading to a compression of the electrical double
      layer around the charged particles. A laboratory-built flat-cell light-scattering
      instrument is used, which allows fast data acquisition and an adjustment of the
      sample cell thickness. To circumvent multiple scattering effects, we use a very
      small sample thickness ( approximately 13 microm). In addition, the refractive
      index difference between the aqueous phase and the particles is reduced by adding
      sucrose to the liquid phase of our suspensions. We are able to characterize the
      structural changes at the very early stages of the destabilization process, where
      no significant effects are yet detected in macroscopic rheological measurements.
      While during the Delta pH destabilization, the scattering curve shows significant
      changes only after some characteristic delay time, it changes continuously during
      the Delta I destabilization. The latter is attributed to the formation of a weak
      pre-gel structure in the suspensions, as a shallow secondary minimum appears in
      the interparticle potential. Data are evaluated by using a HMSA square-well
      structure factor model. Results are in good agreement with those predicted from
      DLVO theory.

PMID- 14972618
TI  - A new emulsion method to synthesize well-defined mesoporous particles.
AB  - A new emulsion method for preparing ordered mesoporous materials with polymer PEG
      as the swelling agent has been explored in the present work. The synthesis
      conditions including the chain length and the PEG concentration, the duration of
      aging, the kind of emulsion, and the time when the swelling agents were added to
      the reaction system are discussed. The results show that with the advantage of
      the emulsion method, the nucleation and growth were controlled very well. The
      nicely spherical particles produced by the emulsion method were more uniform and
      less prone to agglomerate than those produced through the hydrothermal method.
      When different MW PEG were added as swelling agents, the pore size changed
      little: it was centered around 4 nm and had a narrow distribution. When different
      concentrations of PEG were applied, BET surface area, pore size, and pore volume
      changed. To summarize, in the formation of mesoporous materials, polymers such as
      PEG can not only control the pore size from 3 to 70 nm through variation of
      concentration, but also regulate the structures and improve the morphology of
      particles by the chain length of polymers. By adjusting the time of addition of
      the swelling agents, a poroshell mesoporous material was prepared. This method is
      particularly important for those applications that strictly require particle
      uniformity, such as chromatography separation.

PMID- 14972619
TI  - Evolution of fractal-like surface structures in layers of polyacrylonitrile
      solutions by interfacial dynamic processes.
AB  - Solvent evaporation causes concentration and temperature gradients at the free
      surface of a coating polymer solution. Thereby surface-tension-driven flows can
      result in a surface instability with regular structures within the layer.
      Different types of surface structures can occur at spots with thickness
      differences. One can find fractal-like structures especially in the edge zone of
      a layer. The evolution of such fractal-like structures at the surfaces of coating
      solutions of polyacrylonitrile (PAN) in dimethylformamide (DMF) during layer
      hardening is examined. Condensation of water on the surface of the fluid layer
      exerts a strong influence on the formation of these structures. Solutions of PAN
      in DMF are important for the production of ultrafiltration membranes. Such
      membranes are produced by precipitation in a water bath after a short open time.

PMID- 14972620
TI  - Transport across liquid membranes containing vitamin A (retinol acetate).
AB  - The role of the surface activity of vitamin A has been studied in the light of
      the liquid membrane hypothesis of drug action. Transport of relevant amino acids
      such as serine, threonine, arginine, and histidine and various ions such as
      calcium, sodium, and potassium in the presence of liquid membranes generated by
      vitamin A has been studied. The data on the modifications in the permeability of
      relevant amino acids and ions indicate that the liquid membranes generated by
      vitamin A may also play a significant role in its physiological action.

PMID- 14972621
TI  - Molecular dipoles at substrate/film interfaces influencing surface energy of
      Langmuir-Blodgett films.
AB  - Langmuir and Langmuir-Blodgett (LB) films of novel rigid Schiff base amphiphiles
      with different polar groups on aromatic rings have been studied at air/water
      interfaces and on solid substrates. The local surface potentials for the
      different substituents on the aromatic groups of the amphiphiles are correlated
      to the surface energy of LB films on solid substrates. Their contributions are
      probed on high-surface-energy (hsfe) quartz and hydrophobically modified low
      surface-energy (lsfe) quartz. Using theoretical estimates, the long-range effects
      of the substituents of the polar groups on the alkyl chains have been studied
      from charge on the carbon and hydrogen atoms of the alkyl tails. The calculations
      indicate that a substituted carbon atom has a charge that is directly dependent
      on the nature of the atoms to which it is attached rather than on the charges of
      any other atoms of the substituents. This work shows that the polar substituents
      on the head group clearly influence the distal methylene groups of the tail.
      Thus, any treatment, either theoretical or experimental, of these films in
      contact with solid substrates should include the local relative permitivities of
      the polar moieties, which seem to play an important role in determining
      macroscopic properties such as surface energy.

PMID- 14972622
TI  - A new normalization method for determination of colloidal fouling potential in
      membrane processes.
AB  - Normalization of permeate flux data is widely used to characterize membrane
      fouling under different experimental conditions. The main intention of
      normalization is to allow a fair comparison of feed water fouling potentials by
      eliminating the effects of different operational parameters used in the
      experiments, such as net driving pressure and clean-membrane resistance. However,
      it was demonstrated that the commonly used intuitive normalization methods
      usually could not serve their intended purpose. In this study, a new
      normalization method was proposed for characterizing water-fouling potential
      based on fundamental principles of membrane fouling. The intention of this
      normalization method was to define a fouling potential for feed water that was
      independent of, or at least, not strongly affected by operational conditions.
      Laboratory-scale ultrafiltration fouling tests were conducted under different
      colloid sizes, concentrations, and driving pressures. The experiments showed that
      the fouling potentials defined by the newly proposed normalization method were
      linearly related to the colloid concentration of the feed water and that the
      effect of operational conditions used in the fouling experiments on the fouling
      potential was minimal.

PMID- 14972623
TI  - The solid surface free energy calculation. I. In defense of the multicomponent
      approach.
AB  - The acid-base approach to the calculation of solid surface free energy and liquid
      liquid interfacial tensions is a practical example of application of correlation
      analysis, and thus it is an approximate approach. In these limits, and provided
      that wide and well-obtained sets of contact angles or interfacial tension data
      are used for their computation, surface tension components can be considered as
      material properties. Although their numerical value depends on the
      characteristics of the chosen reference material, their chemical meaning is
      independent on the selected scale. Contact angles contain accessible information
      about intermolecular forces; using surface tension component (STC) acid-base
      theory, one can extract this information only making very careful use of the
      mathematical apparatus of correlation analysis. The specific mathematical methods
      used to obtain these results are illustrated by using as an example a base of
      data obtained by the supporters of the equation-of-state theory (EQS). The
      achievements are appreciably good and the agreement between STC and EQS is
      discussed.

PMID- 14972624
TI  - The solid surface free energy calculation; II. The limits of the Zisman and of
      the "equation-of-state" approaches.
AB  - This paper follows the "defense" of the Good-van Oss-Chaudhury (GvOC) acid-base
      approach made in Part I and carries out a detailed analysis of the Zisman
      critical surface energy and, mainly, of the Neumann equation-of-state (EQS)
      theory. The analysis is made on both a "practical" and a theoretical basis,
      trying to highlight the acceptable fitting results of axisymmetric drop shape
      analysis (ADSA) methods and their independence of the assumed thermodynamic
      foundations of EQS. Some new and original criticisms of the EQS approach are
      raised and it is shown that other purely semiempirical models, represented by
      different fitting equations with the same number of parameters, can represent the
      data measured by ADSA method with the same goodness as EQS. The equation of state
      appears as one of many semiempirical approaches for the evaluation of surface
      free energy of solids. Independent of the previous analysis, the criteria used in
      ADSA measurements are evaluated and some comments made on them.

PMID- 14972625
TI  - Motion of foam films in diverging-converging channels.
AB  - Existing theories of the motion of foam films in capillaries often assimilate the
      pressure drop over the foam films to the static capillary pressure obtained from
      the Young-Laplace equation. Hence, they ignore the contribution of dynamic
      effects associated with the rapid stretching and contraction of the foam films to
      the overall viscous dissipation. This paper reports an investigation of the
      motion of foam films in axisymmetric diverging-converging channels, taking into
      account surface viscosity and elasticity. First, a phenomenological theory for
      the motion of the foam films is developed using simple physical arguments. We
      show that the displacement of the film obeys a nonlinear second-order
      differential equation, which can be solved numerically for the (dimensionless)
      distance from the inlet and the pressure drop as a function of time. Experiments
      with foam film motion, conducted using glass diverging-converging channels
      (minimum radius = 3.00 +/- 0,01 mm, maximum diameter = 7,98 +/- 0,01 mm) and
      nitrogen foam stabilized with sodium dodecyl sulfate (SDS) in brine, are
      discussed. For a single film motion in the diverging channel, we find that (a)
      the static pressure drop is a concave-upward function of distance and decreases
      from 1.0 to about 0.3, whereas (b) the dynamic pressure drop is concave downward
      and increases from 1 to a maximum of 1.3 and then decreases to 0.7. In the
      converging channel both the static and dynamic pressure drops are concave
      downward functions, but the dynamic pressure drop values are always higher than
      the static ones. For two films the motions were found to be rather sensitive to
      the initial arrangement in the channel. The experiments are found to be in
      excellent agreement with the theoretical predictions. These observations imply
      that the large flow resistance obtained during foam flow in granular porous
      media, where converging-diverging channels are abundant, is largely due to the
      surface elasticity and viscosity of the films.

PMID- 14972626
TI  - Fluorescence resonance energy transfer-a spectroscopic probe for organized
      surfactant media.
AB  - Dyes commonly used as biological labels have been used to probe resonance energy
      transfer in organized media. In neat water, energy transfer between the dye pairs
      fluorescein (donor):Nile red (acceptor) and acridine orange (donor):Nile red
      (acceptor) has a very low probability of occurrence. This study shows that the
      rate constant of energy transfer increases by more than an order of magnitude in
      organized surfactant media, viz., micelles and reverse micelles of the surfactant
      Triton X-100. The reverse micelles provide a better medium for energy transfer
      than the micelles. The energy transfer studies also provide an idea about the
      location and proximity of donor and acceptor dyes within the various organized
      media. Assuming Poissonian statistics for dye distribution, the donor-acceptor
      distances within micelles and reverse micelles are determined from energy
      transfer parameters. Acridine orange has been found to function better as a donor
      than fluorescein. This may be due to steric and electrostatic factors.

PMID- 14972627
TI  - Changes in the rheological and colloidal properties of paper coating liquids with
      paper-yellowing inhibition additives.
AB  - This is an investigation of the effect of paper-yellowing inhibitors on the
      rheological, colloidal, and interfacial properties of paper-coating liquids and
      the associated changes in the liquid surface microstructure. In addition to
      rheological measurements, we measured the zeta potential and imaged the surface
      microstructure of coating liquids by transmission electron microscopy (TEM) using
      an advanced Pt/C replica technique. The zeta potential is related to the
      concentration of added inhibitors. The images reveal interparticle structuring
      with increasing concentration of inhibitors. The structuring is related to the
      interaction between the coating liquids and the inhibitors. It was also found
      that the viscosity and the elastic modulus increased with inhibitor
      concentration. The significant changes in mixture properties due to the additives
      show the importance of the rheological and surface characterization of liquids
      and the ensuing effect on the corresponding engineering process.

PMID- 14972628
TI  - Stability and demulsification of emulsions stabilized by asphaltenes or resins.
AB  - Experimental data are presented to show the influence of asphaltenes and resins
      on the stability and demulsification of emulsions. It was found that emulsion
      stability was related to the concentrations of the asphaltene and resin in the
      crude oil, and the state of dispersion of the asphaltenes and resins (molecular
      vs colloidal) was critical to the strength or rigidity of interfacial films and
      hence to the stability of the emulsions. Based on this research, a possible
      emulsion minimization approach in refineries, which can be implemented utilizing
      microwave radiation, is also suggested. Comparing with conventional heating,
      microwave radiation can enhance the demulsification rate by an order of
      magnitude. The demulsification efficiency reaches 100% in a very short time under
      microwave radiation.

PMID- 14972629
TI  - Cutin and suberin monomers are membrane perturbants.
AB  - The interaction between cutin and suberin monomers, i.e., omega -hydroxylpalmitic
      acid, alpha, omega -hexadecanedioic acid, alpha, omega --hexadecanediol, 12
      hydroxylstearic acid, and phospholipid vesicles biomimicking the lipid structure
      of plant cell membranes has been studied by optical and transmission electron
      microscopy, quasielastic light scattering, differential scanning calorimetry, and
      (31)P solid-state NMR. Monomers were shown to penetrate model membranes until a
      molar ratio of 30%, modulating their gel to fluid-phase transition, after which
      monomer crystals also formed in solution. These monomers induced a decrease of
      the phospholipid vesicle size from several micrometers to about 300 nm. The
      biological implications of these findings are discussed.

PMID- 14972630
TI  - Internet-based patient education and support interventions: a review of
      evaluation studies and directions for future research.
AB  - The Internet provides patients, families, and health providers with unparalleled
      opportunities to learn, inform, and communicate with one another. This paper is a
      review of studies that have evaluated the impact of professionally facilitated
      Internet-based programs for diverse clinical populations on health outcomes,
      utilization, and user satisfaction. The findings suggest that some outcomes in
      certain groups can be moderately improved and that user satisfaction has been
      generally positive. Given the increasing need to provide timely and effective
      patient-centered care, a stronger evidence base for eHealth applications must be
      established before broader deployment of such programs will take place.

PMID- 14972631
TI  - Sample size calculator for cluster randomized trials.
AB  - Cluster randomized trials, where individuals are randomized in groups are
      increasingly being used in healthcare evaluation. The adoption of a clustered
      design has implications for design, conduct and analysis of studies. In
      particular, standard sample sizes have to be inflated for cluster designs, as
      outcomes for individuals within clusters may be correlated; inflation can be
      achieved either by increasing the cluster size or by increasing the number of
      clusters in the study. A sample size calculator is presented for calculating
      appropriate sample sizes for cluster trials, whilst allowing the implications of
      both methods of inflation to be considered.

PMID- 14972632
TI  - Three-dimensional visualization of protein interaction networks.
AB  - Protein interaction networks provide us with contextual information within which
      protein function can be interpreted and will assist many biomedical studies. We
      have developed a new force-directed layout algorithm for visualizing protein
      interactions in three-dimensional space. Our algorithm divides nodes into three
      groups based on their interacting properties: bi-connected sub-graph in the
      center, terminal nodes at the outermost region, and the rest in between them.
      Experimental results show that our algorithm efficiently generates a clear and
      aesthetically pleasing drawing of large-scale protein interaction networks and
      that it is an order of magnitude faster than other force-directed layouts.

PMID- 14972633
TI  - Computer assisted optimization of an electromagnetic transducer design for
      implantable hearing aids.
AB  - A simple, contactless electromagnetic transducer design for implantable hearing
      aids is investigated. It consists of a coil and a permanent magnet, both of which
      are intended for implantation in the middle ear. The transducer is modeled and
      optimized using computer simulations, followed by experimental verification. It
      is shown that the proposed transducer design can, because of its size and
      geometry, allow implantation through the external auditory canal, and provide a
      sufficiently high acoustic output corresponding to approximately 120 dB sound
      pressure level. It can be optimized to be tolerant of radial displacements
      between coil and magnet of up to 1 mm.

PMID- 14972634
TI  - Computer investigation of ACL orientation during passive range of motion.
AB  - No quantitative data are reported in the literature regarding the orientation of
      anterior cruciate ligament (ACL) fibers during passive range of motion. In this
      study we performed an original qualitative and quantitative analysis in eight
      cadaver knees, examining ACL elongation and 3D orientation. Computer elaboration
      of anatomical and kinematic data obtained by a six degrees-of-freedom
      electrogoniometer enabled a mathematical and statistical evaluation of the 3D
      behavior of the ACL. Our data confirmed the isometric behavior of ACL. The
      inclination of ACL with respect to the tibial plateau decreases with flexion from
      56 degrees to 33 degrees. Orientation of ACL with respect to the femoral notch
      increases with flexion from 4 degrees to 58 degrees. The ACL orientation in a
      medio-lateral direction changes from 24 degrees to 52 degrees. The postero
      lateral and the antero-medial bundle have different angular variations, mainly
      with respect to the tibial plateau and medio-lateral direction. This quantitative
      and qualitative information not only increases the anatomical knowledge of the
      ACL, but could also be important in developing or improving the surgical strategy
      for ACL reconstruction.

PMID- 14972635
TI  - The detection of impedance cardiogram characteristic points using wavelet
      transform.
AB  - A novel impedance cardiograph event detection method using wavelet transform is
      proposed. When compared to the C and E points in the pressure-volume loop, the
      wavelet method performs significantly better than the traditional method (P <
      0.05) in the B and X points detection even after the addition of 20% artificial
      noise into the test signal. Nevertheless, the SVs estimated by ICG are poorly
      correlated with values measured by the conductance catheter.

PMID- 14972636
TI  - A high resolution computer model for sound propagation in the human thorax based
      on the Visible Human data set.
AB  - A parallel supercomputer model based on realistic tissue data is developed for
      sound propagation in the human thorax and the sound propagation behavior is
      analyzed under various conditions using artificial sound sources. The model uses
      the Visible Human male data set for a realistic representation of the human
      thorax. The results were analyzed in time and frequency domains. The analysis
      suggests that lower frequencies of around 100 Hz are more effectively transmitted
      through the thorax and that the spatial confinement of sound waves within the
      thorax results in a resonance effect at around 1500 Hz. The results confirm
      previous studies that show the size of the thorax plays a significant role in the
      type of sound generated at the chest wall.

PMID- 14972637
TI  - Iron assessment tests: transferrin receptor vis-a-vis zinc protoporphyrin.
AB  - OBJECTIVES: To review and compare the biochemical, analytical, and clinical
      features of two relatively new tests for assessing iron status and diagnosing
      iron disorders, namely, the serum transferrin receptor concentration (sTfR) and
      the erythrocyte zinc protoporphyrin/heme ratio (ZnPP/H). To consider the merits
      of each test for the diagnosis of iron disorders with emphasis on iron-deficient
      erythropoiesis, especially in the clinically important preanemia stage of iron
      depletion. CONCLUSIONS: Although the basic biochemical mechanisms underlying the
      two tests are very different, both of these tests are noteworthy because they are
      considered to reflect iron status in the bone marrow. The principal advantage to
      serum transferrin receptor is the lack of a response to anemia of chronic disease
      (ACD), which affects other iron status indicators, for example, ferritin and
      transferrin saturation. The principal advantage to erythrocyte zinc
      protoporphyrin is low cost, but point-of-care testing and simplicity can also be
      advantages. Both serum transferrin receptor and erythrocyte zinc protoporphyrin
      have been demonstrated to be useful in a variety of clinical situations. Serum
      transferrin receptor can be best used in diagnosing iron disorders, especially
      for patients with pathologies that may affect iron metabolism. Erythrocyte zinc
      protoporphyrin can be best used as a primary screening test for assessing iron
      status, especially in patients likely to have uncomplicated iron deficiency.
      While these applications are primary, both tests are more broadly useful, for
      example, in monitoring iron therapy.

PMID- 14972638
TI  - Urinary screening for methylphenidate (Ritalin) abuse: a comparison of liquid
      chromatography-tandem mass spectrometry, gas chromatography-mass spectrometry,
      and immunoassay methods.
AB  - OBJECTIVE: To develop a routine method for detecting methylphenidate (Ritalin)
      use among drug abusers using liquid chromatography-tandem mass spectrometry
      (LC/MS/MS). The new methodology was designed to replace less reliable and/or more
      expensive and time-consuming techniques (GC/MS and ELISA) currently employed in
      our laboratory, and to provide a combined one-step screening and confirmation
      LC/MS/MS method. DESIGN AND METHODS: Because methylphenidate abuse is very
      prevalent in Saskatchewan, there is a demand to provide high volume urine
      screening both to detect abuse, and to monitor compliance. Random urine samples
      sent for drugs of abuse testing, standards, and controls were diluted 1:100 in
      methanol. Diluted specimens were injected directly into an Agilent 1100 liquid
      chromatograph coupled to a Sciex API 2000 mass spectrometer. The method utilized
      selected reaction monitoring (SRM) as well as an electrospray ionization source
      (EIS) to detect both urinary methylphenidate and the more prevalent metabolite,
      ritalinic acid (RA). RESULTS: There appeared to be little or no sacrifice in
      sensitivity because the higher dilutions exhibited much less matrix effect. Limit
      of quantitation (LOQ) for methylphenidate was 100 nM and 500 nM for RA. Linear
      calibration curves from 100 to 1000 nM for Ritalin and 500 to 5000 nM for RA were
      acquired. Imprecision of spiked and true specimens did not exceed 10% and at the
      LOQ, it was less than 20%. CONCLUSIONS: A rapid, sensitive, reliable, and highly
      specific method by LC/MS/MS for detecting methylphenidate and its metabolite, RA,
      were developed. Both the cost and performance of the LC/MS/MS method were
      superior to GC/MS or ELISA, and it allows use of a single rapid procedure for
      both screening and confirmation.

PMID- 14972639
TI  - Short and long-term variation of plasma glycine betaine concentrations in humans.
AB  - BACKGROUND: Glycine betaine is important in cell volume regulation and in
      remethylating homocysteine, a vascular risk factor. OBJECTIVE: We investigated
      changes in circulating glycine betaine concentrations in human volunteers both
      under acute osmotic stress and over longer time scales. DESIGN: Plasma glycine
      betaine concentrations were measured in normal human volunteers in three studies:
      (1) during acute diuresis and antidiuresis; (2) during prolonged diuresis for 5
      days, and antidiuresis for 5 days followed by further diuresis for the final 5
      days; (3) repeated samples taken 3 years apart. RESULTS: Circulating glycine
      betaine concentrations remained almost unchanged for several hours after acute
      diuretic or antidiuretic stresses. There was more (3-10-fold) interindividual
      variation than intraindividual variation. A similar pattern was found on day 15
      of the study. In a 3-year follow-up, plasma glycine betaine concentrations on the
      two occasions were highly correlated with no systematic change, showing that
      individual set points remain stable for years. In contrast, there was no
      relationship among plasma proline betaine concentrations at these times. Urinary
      glycine betaine excretions measured 3 years apart were also found to correlate
      once the perturbing effect of dietary proline betaine excretion was allowed for.
      CONCLUSIONS: Human circulating glycine betaine is homeostatically controlled with
      a distinct control value for each individual. In contrast, peripheral blood
      concentrations of proline betaine, which is present in the diet (and has no known
      metabolic or physiological role in mammals), is not controlled.

PMID- 14972640
TI  - High-performance liquid chromatographic method with column-switching and post
      column reaction for determination of serotonin levels in platelet-poor plasma.
AB  - OBJECTIVES: Measurement of serotonin concentrations in blood is considered to be
      important for the clinical studies of diseases involving vascular endothelial
      injury. We have developed a high-performance liquid chromatographic (HPLC) method
      for measurement of serotonin level in platelet-poor plasma (PPP). METHODS: Venous
      blood samples were collected using vacuum tubes containing
      ethylenediaminetetraacetic acid (EDTA) dipotassium salt; the optimum
      concentration in blood was 7.4 mmol/l. Serotonin in samples was separated by HPLC
      with a column-switching system, and was specifically converted into a fluorescent
      derivative with benzylamine for convenient detection. RESULTS: The between-day
      assay coefficient of variation for a serotonin level (5.1 nmol/l) in PPP was
      6.2%. The mean concentration of serotonin in PPP in healthy subjects was 5.7 +/-
      3.0 nmol/l. The serotonin levels in PPP in patients with ischemic heart disease
      were significantly higher than those in healthy subjects (P = 0.001).
      CONCLUSIONS: The developed method had sufficient performance to determine
      serotonin levels in PPP from patients with ischemic heart disease.

PMID- 14972641
TI  - A longitudinal study of antioxidant status in phenylketonuric patients.
AB  - OBJECTIVES: To investigate the implications of the three main factors of the
      antioxidant system reported in relation to oxidative damage in phenylketonuric
      patients: selenium, ubiquinone-10 (Q10) and antioxidant enzymes over 3 years of
      metabolic follow-up. DESIGN AND METHODS: Longitudinal study of 46 phenylketonuric
      patients (age range: 6 months-34 years). Antioxidants were measured by atomic
      absorption spectrophotometric, chromatographic and spectrophotometric procedures.
      RESULTS: Plasma selenium concentrations in phenylketonuria (PKU) were not
      different from those of a healthy population. Decreased plasma Q10 concentrations
      were mainly related to the dietary control and the age of patients. Erythrocyte
      catalase activity was significantly decreased in PKU while the other enzyme
      activities were not different from those of a healthy population. CONCLUSION:
      Selenium status is not impaired in phenylketonuric patients under dietary
      treatment. Q10 values tend to decrease with increased patient age. Catalase
      activity was negatively associated with plasma phenylalanine values.

PMID- 14972642
TI  - Circulating cytokines as markers of systemic inflammatory response in severe
      community-acquired pneumonia.
AB  - OBJECTIVES: To assess the influence of empirical antibacterial therapy on
      systemic inflammatory response in patients with severe community-acquired
      pneumonia (CAP). MATERIAL AND METHODS: Thirty consecutive patients with CAP
      meeting systemic inflammatory response syndrome (SIRS) criteria were recruited
      into this study. Blood samples for measurement of interleukin-6 (IL-6),
      interleukin-8 (IL-8), interleukin-10 (IL-10) and C-reactive protein (CRP)
      concentrations were drawn on days 1, 3, 5, 7 and 10. For analysis, these patients
      were divided into two subgroups according to British Thoracic Society (BTS)
      severity score and to clinical response to the initial antibacterial therapy.
      RESULTS: In the group with severe CAP (n= 15), serum concentrations of IL-6 (P =
      0.0001), IL-8, (P = 0.001), IL-10 (P = 0.0001) and CRP (P = 0.0001) were
      significantly higher compared to patients from the non-severe group (n= 15). IL-6
      presented with a sharp decrease between days 1 and 3 in non-responders with
      severe CAP (P = 0.004). IL-6 concentrations on day 1 were significantly
      associated with a response to empirical antibacterial treatment by day 3.
      CONCLUSION: Despite the absence of a clinical response to empirical antibacterial
      treatment as assessed by conventional clinical parameters on day 3 in patients
      with severe CAP meeting SIRS criteria, there was a marked reduction in the degree
      of the systemic inflammatory response as reflected by IL-6 levels.

PMID- 14972643
TI  - Biochemical indicators of cardiac and renal function in a healthy elderly
      population.
AB  - OBJECTIVES: To examine the distributions of NT-proBNP and cystatin C and their
      relation to age, gender, and other physiological factors in an apparently healthy
      elderly population. METHOD: NT-proBNP and cystatin C were analyzed in 407 and 408
      healthy individuals, median age: 65 (range 40-76). RESULTS: Increasing age,
      female gender and CRP were independently associated to higher NT-proBNP levels.
      Age, body mass index, and CRP level were independently associated to the cystatin
      C level. In women and men, < or =65 years, the 97.5th percentile value for NT
      proBNP was 268 ng/l and 184 ng/l, in those older, 391 ng/l and 269 ng/l. For
      those < or =65 years the 97.5th percentile value for cystatin C was 1.12 mg/l,
      and for those older 1.21 mg/l. CONCLUSION: In a healthy elderly population, NT
      proBNP is influenced by age and gender, whereas cystatin C is influenced by age
      but not by gender. Both markers seem to be associated to the CRP level.

PMID- 14972644
TI  - Investigation of the chronic effects of NPY by subcutaneous implantation of 6-23
      cells producing NPY in WAG rats.
AB  - OBJECTIVE: In this experiment, we studied the chronic effects of NPY, as there
      were no data on long-term effects of NPY in vivo. METHODS: Complementary DNA
      encoding NPY was isolated, sequenced and cloned into the expression vector,
      pCEP4. The 6-23 clone 6 cell line was transfected with this clone. Two groups of
      10 adult male WAG rats (180-250 g body weight) were injected with either
      untransfected 6-23 clone 6 or 6-23 clone 6 transfected with NPY cDNA [6-23
      (NPY)]. After 8 weeks, the animals were killed, their plasma assayed for insulin.
      Pancreatic glucagon (PG), by RIA, and plasma glucose were measured. RESULTS: The
      transfected cells were shown to be producing fully processed, bioactive NPY. The
      expression of NPY was also confirmed by Northern blot analysis. The animals
      injected with 6-23 (NPY) cells gained significantly more weight than the
      controls, (on day 54, 31.89 +/- 3.56 vs. 24.1 +/- 4.12 g, n = 10, P < 0.05).
      Plasma insulin and PG increased significantly in NPY animals compared to
      controls. The total RNA extracted from tumours was analysed by Northern blotting
      and showed NPY mRNA expression in NPY animals, but not in controls. CONCLUSION:
      The long-term effects of NPY was confirmed by injection of the cells producing
      this peptide.

PMID- 14972645
TI  - Novel insertion and deletion mutations in the 5'-UTR of the folate receptor-alpha
      gene: an additional contributor to hyperhomocysteinemia?
AB  - OBJECTIVES: To search for mutations in the 5'-UTR and proximal promoter region of
      the folate receptor-alpha (FR-alpha) gene, whose exons are known to be virtually
      free of genetic variation in the population. DESIGN AND METHOD: Seven hundred
      seventy-eight patient samples were screened for mutations between nt -116 and nt
      +207 in the FR-alpha gene using single strand conformation polymorphism (SSCP)
      followed by DNA sequencing. RESULTS: Three patients were found to have a 25-bp
      deletion, c.109_133delCCACTAAACCACAGCTGTCCCCTGG, and three others had a 1-bp A
      insertion, c.-69dupA, so that 0.77% of the patient population showed genetic
      variation already in the 323 bp promoter sequence studied so far. CONCLUSIONS:
      The promoter region of FR-alpha may harbor much more genetic variation than its
      highly conserved exons, and not just isolated, unique mutations. This could be a
      new factor contributing to gene-food interaction explaining part of the
      hyperhomocysteinemia panorama. Extended searches for polymorphisms further
      upstream in the FR-alpha gene are warranted.

PMID- 14972646
TI  - Altered kallikrein 7 and 10 concentrations in cerebrospinal fluid of patients
      with Alzheimer's disease and frontotemporal dementia.
AB  - BACKGROUND: The role of various proteases in the pathogenesis of Alzheimer's
      disease is well documented. Recently, many members of the human tissue kallikrein
      family, a group of 15 secreted serine proteases, were found to be highly
      expressed in the central nervous system (CNS). Some of these enzymes can be
      measured in cerebrospinal fluid (CSF) by using ELISA-type methodologies. METHODS:
      We quantified various kallikreins in CSF of 20 patients with Alzheimer's disease
      (AD), 16 patients with frontotemporal dementia (FTD), and 15 controls. We then
      correlated the levels of various kallikreins with presence of AD or FTD. Among
      all kallikreins measured, detectable levels in CSF were identified for
      kallikreins hK6, hK7, and hK10. Other tested kallikreins (hK5, hK8, hK11, and
      hK13) were unmeasurable. The most notable differences between kallikrein levels
      in CSF and the three groups of subjects were seen between controls and FTD
      patients for hK6 (decrease in FTD; P = 0.017), controls and FTD patients for hK7
      (decrease in FTD; P < 0.001), and controls and AD patients for hK7 (decrease in
      AD; P = 0.019). In addition, significant differences were seen between FTD
      patients or control subjects and patients with AD patients for hK10 (increase in
      AD; P < 0.02). Approximately half of the AD patients had CSF hK10 levels that
      were higher than all patients with FTD except one and all control subjects except
      two. Various kallikrein concentrations in CSF were correlated, the strongest
      correlation seen between hK6 and hK7 (r(s) = 0.58). We also observed a
      statistically significant association between decreasing hK7 concentration in CSF
      and possession of one or two ApoE4 alleles (P = 0.014). CONCLUSIONS: We
      demonstrate for the first time significant alterations of hK6, hK7, and hK10
      concentration in CSF of patients with AD and FTD. Notably, all three kallikreins
      (hK6, hK7, and hK10) are decreased in CSF of FTD patients and hK10 is increased
      in CSF of AD patients, in comparison to control subjects. The possible connection
      between these enzymes and the pathogenesis and progression of AD and FTD needs to
      be further investigated.

PMID- 14972647
TI  - Novel use of the Friedewald formula to tackle anomalous HDL-C results in two
      cases of paraproteinaemia.
AB  - OBJECTIVES: We report here two cases of paraproteinaemia with one falsely low and
      the other dubiously high HDL-cholesterol (HDL-C) results. The spurious results
      seemed to be related to the nature (IgG or IgM) as well as the concentration of
      the paraproteins. DESIGN AND METHODS: We have been using an alternative approach
      to estimate the HDL-C concentration by incorporating into it the LDL-cholesterol
      (LDL-C) value obtained by direct measurements and by back-calculation based on
      the time-honored Friedewald equation in these atypical specimens as an interim
      measure, pending optimization of the Roche direct HDL-C plus assay currently in
      use in our laboratory. RESULTS: This approach is convenient and does not require
      sophisticated instrumentation. What we are suggesting is to tackle this
      analytical problems on HDL-C assay due to paraprotein interference by back
      calculating the HDL-C values from the measured LDL-C and triglyceride values
      using the Friedewald formula and is to be regarded as an alternative way to
      circumvent the interference issue without the need for more elaborative
      laboratory procedures. We do not intend to advocate screening every single HDL-C
      value obtained by the direct method for possible analytical errors using this
      approach. CONCLUSIONS: The back-calculation for HDL-C based on the Friedewald
      formula is conceived by the authors as an alternative and relatively simple way
      to estimate the HDL-C value in the presence of paraprotein interference, in
      particular when there is a minus HDL-C value or when the result is dubiously
      high. By the same token, when the measured HDL-C and the calculated HDL-C do not
      match further investigations would be warranted to safeguard the validity of the
      reported result. It is also, to the best of our knowledge, the first time extra
      bands due to the IgM and IgG paraproteins were demonstrated in the lipoprotein
      electrophoresis plate.

PMID- 14972648
TI  - An update on the prevalence of glucose-6-phosphate dehydrogenase deficiency and
      neonatal jaundice in Tehran neonates.
AB  - OBJECTIVES: The aim of this study was to screen newborns in Tehran for glucose-6
      phosphate dehydrogenase (G6PD) deficiency in relation to hyperbilirubinemia and
      jaundice. DESIGN AND METHODS: We performed quantitative and qualitative red blood
      cell (RBC) G6PD assays in cord blood of 2000 male and female at-term neonates.
      Observations for jaundice and bilirubin determination were made in G6PD-deficient
      and normal groups. Those with severe jaundice were treated with phototherapy or
      exchange transfusion. RESULTS: Our results showed that 2.1% (3.6% of males and
      0.6% of females) was G6PD-deficient. Those with severe jaundice and
      hyperbilirubinemia (160 normal and 17 G6PD-deficient) were hospitalized and
      treated with phototherapy or exchange transfusion. Bilirubin levels in G6PD
      deficient neonates were somewhat higher compared to G6PD-normal babies (18.8 +/-
      2.4 mg/dl [321.5 +/- 41 micromol/l] vs. 15.7 +/- 3.2 mg/dl [268.5 +/- 54.7
      micromol/l]; P < 0.05). G6PD activity was significantly lower in G6PD-deficient
      group than in the normal group (2.1 +/- 0.7 vs. 12.5 +/- 5.0 U/g Hb; P < 0.001).
      CONCLUSION: This study shows that the incidence of G6PD deficiency in newborns of
      Tehran is 2.1%, which is relatively high, and also hyperbilirubinemia and
      jaundice are approximately 3-fold higher in G6PD-deficient group than in the G6PD
      normal group (51% vs. 16%). This emphasizes the necessity of neonatal screening
      on cord blood samples of both sexes for G6PD deficiency and the need to watch
      closely for development of hyperbilirubinemia.

PMID- 14972649
TI  - Serotonergic modulation of intracellular calcium dynamics in neonatal hypoglossal
      motoneurons from mouse.
AB  - (1) Serotonin (5HT)-mediated calcium signaling was investigated in hypoglossal
      motoneurons (HGMs) in brain stem slices of neonatal mice. Electrical activity and
      associated calcium signaling were studied by simultaneous patch clamp recordings
      and high resolution calcium imaging. (2) Bath application of 5HT (5-50 microM)
      depolarized membrane potential of HGMs and generated action potential discharges
      that were accompanied by elevations in intracellular calcium concentrations
      ([Ca2+]i) in the soma and dendrites. Current-evoked bursts of action potentials
      were more intense in the presence of 5HT; however, the corresponding calcium
      signals were reduced. (3) The 5HT2 receptor agonist alpha-Methyl-5HT (25, 50
      microM) had effects on membrane potential, discharge properties and [Ca]i that
      were identical to those observed for 5HT, whereas the 5HT3 receptor agonist 1-(m
      chlorophenyl) biguanide (50 microM) had no effect on membrane properties or
      intracellular calcium levels. (4) 8-OHDPAT (25, 50 microM), a 5HT1A receptor
      agonist, was without effect on steady-state membrane potential or basal [Ca]i.
      Similar to 5HT and alpha-Methyl-5HT, 8-OHDPAT depressed stimulus-evoked calcium
      transients in current and voltage clamp mode. (5) Our results suggest that
      calcium profiles in hypoglossal motoneurons are differentially regulated by 5HT1A
      and 5HT2 receptors. Activation of 5HT1A receptors primarily reduced voltage
      activated Ca2+ signals without a significant impact on basal [Ca]i. In contrast,
      activation of 5HT2 receptors initiated a net inward current followed by membrane
      depolarization, where the resulting pattern of action potential discharges
      represents the essential determinant of global elevations in [Ca2+]i. Taken
      together, our results therefore identify 5HT-dependent signal pathways as a
      versatile tool to modulate hypoglossal motoneuron excitability under various
      physiological and pathophysiological conditions.

PMID- 14972650
TI  - The recovery of blood-nerve barrier in crush nerve injury--a quantitative
      analysis utilizing immunohistochemistry.
AB  - The purpose of this study is to reveal whether the application of
      immunohistochemical examinations to the peripheral nervous system (PNS) can be a
      reliable method for the quantitative analysis of the blood-nerve barrier (BNB)
      and the relationship between restoration of BNB and nerve regeneration. Sciatic
      nerves in rats were examined after nerve crush. Immunohistochemical staining with
      anti-rat endothelial cell antigen-1 (anti-RECA-1) that recognizes endothelial
      cells and anti-endothelial barrier antigen (anti-EBA) for the detection of
      barrier-type endothelial cells were used. Neurofilament for staining axons was
      also performed. A quantitative analysis of the BNB was assessed using the ratio
      of EBA positive cells and RECA-1 positive cells. The ratio of EBA/RECA-1
      decreased significantly 3 days postoperatively and reached its lowest level at
      day 7 in the segment 5 mm proximal and the entire distal stump. The ratio
      gradually recovered from the proximal and the regeneration of axons started a
      week earlier than BNB. The ratio of EBA/RECA-1 applied to the PNS can be a
      reliable method for the quantitative analysis of BNB. In crush injuries, the
      breakdown of BNB occurred simultaneously in the segment 5 mm proximal and the
      entire distal stump; restoration began from the proximal to distal and followed a
      week later to nerve regeneration.

PMID- 14972651
TI  - Activity of peri-oral facial muscles and its coordination with jaw muscles during
      ingestive behavior in awake rabbits.
AB  - To study peri-oral facial muscle activity patterns and coordination with jaw
      muscles during ingestive behavior, electromyographic (EMG) activities in the peri
      oral facial (buccinator: BUC, orbicularis oris: ORB) and jaw (masseter,
      digastric) muscles along with jaw movement trajectories were recorded in awake
      rabbits. A standardized amount of apple in a cylindrical shape was used as the
      test food. The period from food intake to just before swallowing (the masticatory
      sequence) was divided into three masticatory periods (preparatory period,
      rhythmic chewing period and preswallow period) based on the activity pattern of
      jaw muscles and jaw movement trajectories, and jaw movements and EMG activities
      in both the jaw and facial muscles during each masticatory period were assessed.
      Both the jaw and facial muscles were active throughout the masticatory sequence,
      and the activity patterns of facial muscles and the pattern of coordination
      between the facial and jaw muscles varied for each masticatory period. No
      consistent pattern was noted for the BUC activity during the preparatory period,
      whereas the ORB showed tonic activity throughout this period. During the rhythmic
      chewing and preswallow periods, both the ORB and BUC showed jaw-movement-related
      rhythmic bursts. However, significant differences were noted in the burst
      properties in both facial muscles and their temporal correlations with the jaw
      muscle activities between these two periods. Results suggest that the neural
      mechanisms regulating facial muscle activities may differ between the masticatory
      periods, and such mechanisms may contribute to the well-coordinated orofacial
      movements required for smooth masticatory sequence.

PMID- 14972652
TI  - Late onset Tay-Sachs disease in mice with targeted disruption of the Hexa gene:
      behavioral changes and pathology of the central nervous system.
AB  - Tay-Sachs disease is an autosomal recessive neurodegenerative disease resulting
      from a block in the hydrolysis of GM2 ganglioside, an intermediate in ganglioside
      catabolism. The mouse model of Tay-Sachs disease (Hexa -/-) has been described as
      behaviorally indistinguishable from wild type until at least 1 year of age due to
      a sialidase-mediated bypass of the metabolic defect that reduces the rate of GM2
      ganglioside accumulation. In this study, we have followed our mouse model to over
      2 years of age and have documented a significant disease phenotype that is
      reminiscent of the late onset, chronic form of human Tay-Sachs disease. Onset
      occurs at 11-12 months of age and progresses slowly, in parallel with increasing
      storage of GM2 ganglioside. The disease is characterized by hind limb spasticity,
      weight loss, tremors, abnormal posture with lordosis, possible visual impairment,
      and, late in the disease, muscle weakness, clasping of the limbs, and myoclonic
      twitches of the head. Immunodetection of GM2 ganglioside showed that storage
      varies widely in different regions, but is most intense in pyriform cortex,
      hippocampus (CA3 field, subiculum), amygdala, hypothalamus (paraventricular
      supraoptic, ventromedial and arcuate nuclei, and mammilary body), and the
      somatosensory cortex (layer V) in 1- to 2-year-old mutant mice. We suggest that
      the Tay-Sachs mouse model is a phenotypically valid model of disease and may
      provide for a reliable indicator of the impact of therapeutic strategies, in
      particular geared to the late onset, chronic form of human Tay-Sachs disease.

PMID- 14972653
TI  - FK506 reduces infarct volume due to permanent focal cerebral ischemia by
      maintaining BAD turnover and inhibiting cytochrome c release.
AB  - It has been reported that immunosuppressant FK506 inhibited ischemic neuronal
      injury in forebrain ischemia or transient focal cerebral ischemia, but the
      mechanisms of the neuroprotective effect have not been clarified. In permanent
      focal cerebral ischemia, we investigated whether FK506 caused remission of brain
      infarction, and how mechanism was concerned. Male Balb/c mice were subjected to
      permanent middle cerebral artery (MCA) occlusion. They were treated with 1.0 or
      3.0 mg/kg FK506 or vehicle 30 min before ischemia. Infarct volume was assessed by
      2,3,5-triphenyltetrazolium chloride (TTC) method after 24 h. Cytochrome c release
      from mitochondria was evaluated by Western blotting and immunocytochemistry after
      ischemia. Simultaneously, the immunoreactivity of total and phosphorylated BAD
      was also studied using immunocytochemistry. We demonstrated that pretreatment
      with 3.0 mg/kg FK506 salvaged the tissue damage in the infarct rim and
      significantly reduced infarct volume to 75.5% (P<0.05), and FK506 inhibited
      cytochrome c release on 6 h after ischemia for Western blot analysis (P<0.05).
      Immunocytochemical study showed that permanent MCA occlusion increased the amount
      of cytochrome c and total BAD in the cytosol, but not phosphorylated BAD, in the
      ischemic core and the infarct rim as early as 1 h after ischemia, and FK506
      inhibited the increases in the infarct rim. The results suggest that FK506 may,
      at least in part, ameliorate tissue damage due to permanent focal cerebral
      ischemia in the infarct rim through maintaining BAD turnover and inhibiting
      cytochrome c release from mitochondria.

PMID- 14972654
TI  - Anxiety is functionally segregated within the septo-hippocampal system.
AB  - Previous lesion studies have suggested that the septal-hippocampal system is
      involved in fear and anxiety. In this study we examined the effects on anxiety of
      temporary neuronal inhibition of various aspects of the septo-hippocampal system
      in rats. Infusions of tetrodotoxin (TTX) were used to induce reversible lesions
      in the fimbria fornix, medial septum, dorsal hippocampus, and ventral
      hippocampus. To assess anxiety we used the elevated plus-maze and the shock-probe
      burying tests. A reduction in anxiety in the elevated plus-maze is indicated by
      increased open arm exploration, whereas a reduction in anxiety in the shock-probe
      burying test is indicated by decreased burying behavior or increased contacts
      with the shock-probe. The results suggested that inhibition of the septal
      hippocampal system induced site-specific anxiolytic effects that vary in nature.
      Tetrodotoxin lesions of the fimbria fornix increased both open arm exploration
      and the number of shocks taken by the rats, while having no effect on burying
      behavior. Both septal and ventral hippocampal lesions increased open arm
      exploration and decreased burying behavior, but had no effect on the number of
      probe shocks. Finally, TTX lesions of the dorsal hippocampus increased the number
      of shocks taken by the rats, but did not affect open arm activity or burying
      behavior. Neuroanatomical studies indicated that the effect on the number of
      shocks induced by dorsal hippocampal TTX lesions was not likely mediated by the
      amygdala. Collectively, the data suggest that the control of specific anxiety
      reactions is functionally segregated within different aspects of the septo
      hippocampal system.

PMID- 14972655
TI  - Effects of estradiol on immediate early gene expression associated with ovulation
      in lactating rats: role of nutritional status.
AB  - In rats, food restriction during lactation extends lactational infertility, an
      effect that is in part due to attenuated luteinizing hormone (LH) responses to
      the positive feedback effects of estradiol (E2). In cycling rats, rising
      endogenous E2 levels not only induce a surge in LH release, but also increase the
      expression of the immediate early gene Fos in the anteroventral preoptic area
      (AVPV) and within gonadotropin releasing hormone (GnRH) neurons. This experiment
      examined whether the induction of Fos expression in the AVPV and within GnRH
      neurons after E2 treatment varied with stage of lactation and nutritional status.
      Brains of estrogen-treated ad lib fed and food-restricted lactating rats were
      processed for Fos or Fos/GnRH immunocytochemistry on days 15, 20, or 25
      postpartum (pp). Cell counts from both labeling studies showed that on day 15 pp,
      neuronal activation in the AVPV and within GnRH neurons was low and did not
      differ between ad lib fed and food-restricted dams. On day 20 pp, levels of Fos
      like immunoreactivity (FOS-IR) in the AVPV remained low in all dams but were
      significantly higher in ad lib fed dams. By day 25 pp, the ability of E2 to
      induce FOS-IR in the AVPV of food-restricted dams remained compromised. The
      proportion of GnRH cells expressing FOS-IR following E2 stimulation was restored
      to baseline levels by day 20 pp regardless of the nutritional status of the dam.
      These results show that the effects of E2 on neuronal events that correlate with
      the LH surge, are attenuated during lactation. Furthermore, food restriction
      during lactation selectively alters neuronal activation in the AVPV suggesting
      that this area integrates nutritional information to regulate LH release.

PMID- 14972656
TI  - Effects of long-term exposure of lemon essential oil odor on behavioral, hormonal
      and neuronal parameters in male and female rats.
AB  - Behavioral, hormonal and neuronal responses to prolonged exposure to the volatile
      components of essential oil (EO) extracted from citrus lemon were investigated in
      male and female rats. Animals were exposed to the lemon essence for 2 weeks while
      in their cage. Anxiety was then determined with the elevated plus-maze apparatus
      while nociception was evaluated with a phasic thermal pain stimulus (plantar
      test) and with a chemical pain stimulus (formalin test). At the end of the
      experimental sessions, brain areas were dissected to measure beta-endorphin (beta
      EP) concentrations in the hypothalamus and periaqueductal gray matter (PAG).
      Blood samples were collected to determine corticosterone plasma levels. In both
      sexes, prolonged EO exposure decreased the time spent in the open arms of the
      plus-maze apparatus. EO-exposed males and females showed higher thermal
      nociceptive thresholds than controls when tested with the plantar test apparatus.
      EO exposure induced female-specific decreases in formalin-induced pain behaviors
      during the formalin test. beta-EP concentrations in the hypothalamus and PAG were
      affected by EO. Corticosterone was lower in EO-exposed animals of both sexes than
      in their controls. These results suggest that long-term exposure to lemon EO can
      induce significant, at times sex-specific, changes in neuronal circuits involved
      in anxiety and pain.

PMID- 14972657
TI  - Substance P microinjected into the periaqueductal gray matter induces
      antinociception and is released following morphine administration.
AB  - The aims of the present study were to investigate, in rats, the behavioral
      effects of substance P (SP) microinjected into the ventrolateral periaqueductal
      gray (PAG) and the effects of the neurokinin 1 (NK-1) receptor antagonist [d
      Arg1, d-Trp7, 9, Leu11]-substance P (Spantide). The effect of morphine
      administration on the release of SP in the ventrolateral PAG was also
      investigated using microdialysis in awake rats. SP microinjected into the
      ventrolateral part of the PAG induced significant increases in the hindpaw
      withdrawal latencies (HWLs) to thermal and mechanical stimulation as an
      antinociceptive response. The NK-1 receptor antagonist blocked these effects but
      exhibited no antinociceptive effect alone. Subcutaneous administration of
      morphine increased basal SP-like immunoreactivity (SP-LI) release in the
      microdialysate obtained from the ventrolateral PAG of freely moving rats. Our
      results demonstrate that SP injected into the ventrolateral PAG induces an
      antinociceptive effect via activation of NK-1 receptors. Morphine administered
      systemically induces the release of SP in the ventrolateral PAG. We suggest that
      an increased release of SP in the PAG may contribute to opioid antinociception.

PMID- 14972658
TI  - Cholecystokinin modulation of locomotor behavior in rats is sensitized by chronic
      amphetamine and chronic restraint stress exposure.
AB  - DA release in the nucleus accumbens (NAcc) is a critical substrate mediating
      locomotor behavior. Cholecystokinin (CCK) is co-localized with dopamine (DA) in
      up to 90% of mesolimbic DA neurons. We have previously shown that while CCKA
      receptor antagonists generally do not affect locomotor behaviors, systemic
      administration of a CCKA receptor antagonist attenuates amphetamine (AMPH)
      induced locomotion in animals previously treated chronically with AMPH,
      suggesting that chronic stimulant pretreatment may sensitize CCK systems. The
      present studies examined this issue by testing the effects of CCKA antagonists on
      AMPH- and novel environment-induced locomotor activity following two
      manipulations which are known to alter mesolimbic system function: Chronic AMPH
      administration and chronic restraint stress (RS). Additionally, CCK
      immunoreactivity in the mesolimbic system following these manipulations was
      examined using immunohistochemistry. Results indicated that intra-NAcc
      microinjections of the selective CCKA receptor antagonist PD-140548 attenuated
      AMPH-induced and novel environment-induced locomotion only in animals which had
      previously been exposed to chronic AMPH or chronic RS pretreatment. However,
      chronic AMPH and chronic RS did not produce detectable changes in the number of
      CCK-immunostained neurons in the ventral tegmental area (VTA) or substantia nigra
      (SN), or in CCK levels in any of the subregions of the NAcc. Together, these
      results suggest that the role of endogenous CCK in the modulation of locomotor
      behaviors is sensitized following chronic psychostimulant or chronic RS exposure.
      However, this sensitization does not appear to be accompanied by changes in the
      overall basal levels of CCK or in the number of CCK-positive cells within the
      mesoaccumbens system.

PMID- 14972659
TI  - Expression of the iron transporter ferroportin in synaptic vesicles and the blood
      brain barrier.
AB  - Iron homeostasis in the mammalian brain is an important and poorly understood
      subject. Transferrin-bound iron enters the endothelial cells of the blood-brain
      barrier from the systemic circulation, and iron subsequently dissociates from
      transferrin to enter brain parenchyma by an unknown mechanism. In recent years,
      several iron transporters, including the iron importer DMT1 (Ireg1, MTP, DCT1)
      and the iron exporter ferroportin (SLC11A3, Ireg, MTP1) have been cloned and
      characterized. To better understand brain iron homeostasis, we have characterized
      the distribution of ferroportin, the presumed intestinal iron exporter, and have
      evaluated its potential role in regulation of iron homeostasis in the central
      nervous system. We discovered using in situ hybridization and
      immunohistochemistry that ferroportin is expressed in the endothelial cells of
      the blood-brain barrier, in neurons, oligodendrocytes, astrocytes, and the
      choroid plexus and ependymal cells. In addition, we discovered using techniques
      of immunoelectron microscopy and biochemical purification of synaptic vesicles
      that ferroportin is associated with synaptic vesicles. In the blood-brain
      barrier, it is likely that ferroportin serves as a molecular transporter of iron
      on the abluminal membrane of polarized endothelial cells. The role of ferroportin
      in synaptic vesicles is unknown, but its presence at that site may prove to be of
      great importance in neuronal iron toxicity. The widespread representation of
      ferroportin at sites such as the blood-brain barrier and synaptic vesicles raises
      the possibility that trafficking of elemental iron may be instrumental in the
      distribution of iron in the central nervous system.

PMID- 14972660
TI  - Effect of lesioning the suprachiasmatic nuclei on behavioral despair in rats.
AB  - The suprachiasmatic nucleus (SCN) is involved in regulating many biological
      rhythms. Several lines of research implicate the SCN in affective behavior. The
      SCN is directly involved in regulating the daily rhythms of the hypothalamo
      pituitary-adrenal (HPA) axis hormones involved in stress. Bilateral lesions of
      the SCN disrupt both the rhythms and the basal levels of the HPA axis hormones
      involved in coping with stress. Moreover, stress can affect the biological
      rhythms regulated by the SCN, and disruption of biological rhythms in turn can
      cause stress. The present study assessed the effect of bilateral destruction of
      the SCN on behavioral despair, an animal model of depression sensitive to
      antidepressant treatment. The results indicate that bilateral destruction of the
      SCN results in reduced immobility in the second forced swimming test (FST)
      compared to sham controls and animals with incomplete lesions. These results
      indicate that bilateral destruction of the SCN has a protective effect in the
      induction of behavioral despair which may arise out of disruption of the
      secretion of the HPA axis hormones and/or of the neural connections between the
      SCN and the limbic structures that modulate the response to swim stress.

PMID- 14972661
TI  - Functional validation of adult hippocampal organotypic cultures as an in vitro
      model of brain injury.
AB  - To determine whether hippocampal pyramidal neurons retain authentic functional
      properties in mature organotypic culture, hippocampal slice cultures were
      established from young adult rats (P20-21). Cultures maintained 7 days in vitro
      retained tight organization of neuronal layers, as opposed to the widening
      restructure of pyramidal neurons often observed in perinatal slices. CA3 and CA1
      pyramidal neurons fired action potentials in response to current injection and
      exhibited spontaneous and evoked synaptic currents, indicating intact neuronal
      function and normal hippocampal neural circuitry. We also tested neuronal
      sensitivity of slice cultures to ischemic injury. Acute ischemic paradigm
      resulted in selective death of pyramidal neurons in the CA1 region, which was
      prevented by treatment with an NMDA-antagonist, MK-801. Robust efflux of
      excitatory and inhibitory amino acid neurotransmitters was detected during
      ischemia, consistent with changes shown in acute slices. In summary, hippocampal
      organotypic cultures prepared from young adult rats maintained neuronal
      architecture and synaptic activity in vitro and can be used in parallel with an
      acute slice system to model mature brain tissue to examine ischemic
      pathophysiology and neuroprotective treatment.

PMID- 14972662
TI  - Nuclear localization of the hypoxia-regulated pro-apoptotic protein BNIP3 after
      global brain ischemia in the rat hippocampus.
AB  - The 19 kD interacting protein 3, Nip3/BNIP3, is a pro-apoptotic member of the Bcl
      2 family induced during hypoxia via the hypoxia-inducible factor (HIF) 1. BNIP3
      has been linked to both apoptotic and necrotic cell death involving mitochondrial
      permeability transition. Since apoptotic and necrotic mechanisms may occur in
      brain ischemia, immunohistochemical changes of BNIP3 were studied at 1, 2, 3 and
      7 days after transient global brain ischemia (12.5 min) in ventilated
      normothermic rats. In control brains, BNIP3-like immunoreactivity was moderately
      strong in neuronal processes or cytoplasm and absent in the nucleus. In the
      ischemia-vulnerable CA1 neurons, BNIP3-positive granules were seen in the nucleus
      at 1 and 2 days, and these neurons were damaged at 3 and 7 days. The resistant
      CA3 neurons showed nuclear BNIP3 labeling by 1 day and then returned to the
      normal state. BNIP3-positive granules did not overlap with the nucleolus.
      Constitutively expressed BNIP3 may participate in apoptotic and necrotic
      processes after brain ischemia. Nuclear location of BNIP3 after brain ischemia
      indicates a novel role for the regulation of cell survival in neurons or a
      general disturbance of the nuclear envelope.

PMID- 14972663
TI  - Complexity of tissue injury-induced nociceptive discharge of dorsal horn wide
      dynamic range neurons in the rat, correlation with the effect of systemic
      morphine.
AB  - Persistent discharge of wide dynamic range (WDR) neurons was recorded from lumbar
      dorsal horn of anesthetized rats following subcutaneous bee venom injection into
      the receptive field. To quantitatively describe the complexity of this
      nociceptive activity, we computed the approximate entropy (ApEn) for each sampled
      interspike interval (ISI) series. A larger value of ApEn indicates higher
      complexity or less regularity and vice versa. The ApEn value varied across
      different WDR neurons tested, and for each neuron the ApEn remained constant
      through the 1-h discharge though the average ISI of the sampled data increased
      progressively with time (16 neurons). A low dose of intravenous morphine (0.3
      mg/kg) depressed the activity of WDR neurons differentially, and the degree of
      this inhibition showed a significant correlation with the value of ApEn (P<0.001,
      27 neurons, Spearman's correlation test). The present results suggest that the
      complexity feature of WDR neurons is various under tissue injury state, and for
      each single WDR neuron the complexity feature is relatively independent of the
      strength of peripheral noxious input and cannot be fully described in terms of
      average firing rate. Moreover, the response of the nociceptive discharge to
      analgesics may be related to the nonlinear dynamics feature of nociceptive
      neurons, which can be quantitatively characterized by the degree of complexity.

PMID- 14972664
TI  - Roles of the melanocortin-4 receptor in antipyretic and hyperthermic actions of
      centrally administered alpha-MSH.
AB  - Activation of central melanocortin receptors (MCR) inhibits fever but can also
      stimulate thermogenesis, and the mechanisms involved are unknown. To determine
      whether the long-recognized antipyretic effect of exogenous alpha-MSH is mediated
      by the melanocortin-4 receptor (MC4R), and what thermoeffector systems are
      involved, we tested the effects of intracerebroventricular (i.c.v.) injection of
      alpha-MSH on lipopolysaccharide (LPS, 30 microg/kg i.p.)-induced fever in rats,
      in the presence and absence of the selective MC4R antagonist HS014. Treatment
      with alpha-MSH (1 microg, i.c.v.) suppressed LPS-induced increases in core body
      temperature (Tc), whereas a lower dose (300 ng) was ineffective. Nevertheless,
      both alpha-MSH doses effectively inhibited LPS-induced peripheral
      vasoconstriction, the principal heat-conserving thermoeffector, as determined by
      changes in tail skin temperature (Tsk). This implies that the net antipyretic
      effect of alpha-MSH cannot be accounted for solely by modulation of heat loss
      effectors, but also involves other mechanisms. Surprisingly, central MC4-R
      blockade by coinjected HS014 (1 microg) not only prevented, but reversed the
      effect of alpha-MSH (1 microg) on Tc, thus resulting in augmented LPS-induced
      fever. In afebrile rats, alpha-MSH infusion caused a modest transient increase in
      Tc that was blocked by coinjected HS014, but was not accompanied by altered Tsk.
      Overall, the results support the hypothesis that the MC4R mediates the
      antipyretic effects of alpha-MSH. Paradoxically, in the presence of
      pharmacological MC4-R blockade during fever, exogenous alpha-MSH can exacerbate
      fever, probably by acting via other central MCR subtype(s). In normal animals,
      centrally injected alpha-MSH exerts a hyperthermic effect that is mediated by the
      MC4R, consistent with recent evidence that MC4R activation promotes energy
      expenditure in normal states through stimulation of thermogenesis.

PMID- 14972665
TI  - Antioxidant defence of the neonatal rat brain against acute hyperammonemia.
AB  - Oxidative stress associated with the presence of elevated concentrations of
      ammonia in the brain has been proposed as one possible mechanism involved in
      ammonia toxicity. In a previous study [Brain Res.973 (2003) 31], we reported that
      neonatal rats are more resistant to acute ammonia toxicity than adult rats. In
      the present work, we studied the antioxidant status of the brain in
      hyperammonemic neonatal rats. Increased activities of the antioxidant enzymes and
      enhanced glutathione content were found in the brains of the hyperammonemic
      neonatal rats as compared to the controls. In addition, no changes in brain
      reactive oxygen species (ROS) levels and lipid peroxidation due to hyperammonemia
      were found. Therefore, acute ammonia intoxication does not induce oxidative
      stress in neonatal rats, a fact that may explain the resistance against
      hyperammonemia shown by neonatal rats.

PMID- 14972666
TI  - The blockade by phencyclidine of glutamate-induced intracellular calcium increase
      in cultured neocortical neurons.
AB  - A calcium imaging technique combined with a confocal laser scanning microscope
      (CLSM) was applied to investigate the effects of phencyclidine (PCP) on glutamate
      induced calcium increases in same group of primary cultured neocortical neurons.
      Non-N-methyl-D-aspartate (NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline
      2,3-dione (CNQX) alone did not significantly alter glutamate-induced changes of
      fluorescence (89.6%), while addition of PCP greatly blocked increases in
      fluorescence to 32.6% of the glutamate response. Competitive NMDA receptor
      antagonist DL-2-amino-5-phosphonovaleric acid (APV) alone and the addition of PCP
      reduced glutamate responses to 30.5% and 21.2%, respectively. These data clearly
      demonstrate that the neuropharmacological properties of PCP may function through
      its blockade of the NMDA receptor.

PMID- 14972667
TI  - Heightened embarrassability discriminates between panic disorder patients with
      and without agoraphobia.
AB  - Embarrassability refers to an individual's general susceptibility to becoming
      embarrassed and is closely linked to another personality characteristic known as
      fear of negative evaluation. To find out if panic disorder patients with and
      without agoraphobia differ in terms of embarrassability and fear of negative
      evaluation 100 patients with a DSM-III-R diagnosis of panic disorder with
      agoraphobia, 30 patients with a DSM-III-R diagnosis of uncomplicated panic
      disorder and 80 controls were administered the Embarrassability Scale and the 12
      item version of the Fear of Negative Evaluation Scale. Depressive mood in the
      clinical group was assessed with the help of the Beck Depression Inventory.
      Comparisons between these three groups, between patients with mild, moderate, and
      severe phobic avoidance and between male and female subjects were carried out.
      Patients with agoraphobic avoidance showed significantly higher scores on both
      scales than patients with uncomplicated panic disorder and controls and women
      generally showed higher embarrassability scores than men. We conclude that
      heightened embarrassability is an important characteristic of patients suffering
      from panic disorder with agoraphobia.

PMID- 14972668
TI  - Anticipatory processing in social anxiety: two pilot studies.
AB  - Two studies investigating the cognitive processes associated with anticipatory
      social anxiety are reported. Study 1 used a semi-structured interview to compare
      high and low socially anxious individuals ( [Formula: see text] per group) in
      terms of their reported mental processes during periods of anticipatory social
      anxiety. Study 2 investigated the anxiety inducing effects of the mental
      processes that were shown to be characteristic of high socially anxious
      individuals in Study 1. Prior to giving a speech, high and low socially anxious
      individuals ( [Formula: see text] per group) either engaged in these processes or
      performed a distraction task. The results of Study 1 were broadly consistent with
      Clark and Wells' (In: R.G. Heimberg, M. Liebowitz, D.A. Hope, F.R. Schneier
      (Eds.), Social phobia: Diagnosis, Assessment and Treatment (pp. 69-93). New York:
      Guilford Press, 1995) hypotheses about the nature of anticipatory processing in
      social anxiety. Study 2 showed that, compared to distraction, engaging in the
      mental processes characteristic of high socially anxious individuals was
      associated with sustained elevations of anticipatory anxiety in both high and low
      socially anxious individuals, and led to higher levels of peak anxiety during the
      speech. The findings suggest that high and low socially anxious individuals show
      systematic differences in their mental processes prior to a stressful social
      event, and are consistent with the suggestion that these differences play an
      important role in sustaining anticipatory anxiety.

PMID- 14972669
TI  - An unusual case of a wasp phobic.
AB  - This study concerns a woman with a very specific phobia of free-flying wasps. Her
      underlying and disabling belief was that she was allergic to wasp venom and, if
      stung, would certainly die. A behavioural approach, such as systematic
      desensitization and exposure, was not thought suitable because of the patient's
      pattern of fear. Instead, the treatment of choice was an allergy test to directly
      challenge her belief. The allergy test was negative and led to a dramatic
      improvement which was maintained 1 year after treatment.

PMID- 14972670
TI  - The role of negative interpretations of grief reactions in emotional problems
      after bereavement.
AB  - This study explored the role of negative interpretations of grief reactions in
      emotional problems after bereavement, with 234 individuals who had been
      confronted with the death of a close relative. It was found that negative
      interpretations of grief reactions were highly associated with the degree to
      which these reactions were experienced as distressing, the degree to which
      mourners engaged in avoidance behaviours and the severity of symptoms of
      traumatic grief and depression, even when controlling for the frequency of grief
      reactions and the influence of relevant background variables. Furthermore,
      behavioural and cognitive avoidance strategies were significantly related to the
      severity of traumatic grief and depression. Negative interpretations of grief
      reactions and rumination explained most variance in symptom severity, when
      controlling for the shared variance between the predictor variables. The results
      have implications for the treatment of emotional problems after bereavement.

PMID- 14972671
TI  - Differences between those who panic by day and those who also panic by night.
AB  - This study examined the characteristics, correlates, background demographic, and
      personality variables associated with panic among those who panic exclusively
      from a waking state and those who also panic out of sleep. Participants were
      recruited through advertising in print media and through anxiety/panic support
      groups. Some group differences in the characteristics of panic and the
      associations between panic and other variables were found. Specifically, levels
      of anxiety sensitivity were higher, panic duration was longer, and panic was less
      strongly related to catastrophic cognitions for the group that experienced
      nocturnal panic. These differences are cautiously interpreted as not supporting a
      "strong" cognitive theory of panic initiation.

PMID- 14972672
TI  - Masculine Gender Role Stress: a potential predictor of phobic and obsessive
      compulsive behaviour.
AB  - Eisler and Blalock (Clin. Psychol. Rev. 11 (1991) 45) developed a cognitively
      mediated notion of Masculine Gender Role Stress (MGRS) which assumes that rigid
      commitment to masculine schemata for appraisal and coping with life's problems
      may both produce stress and result in dysfunctional coping patterns in men.
      Previous findings obtained in a non-clinical sample pointed to the ability of the
      MGRS General scale to predict different forms of irrational fears. Using a
      predominantly psychologically distressed sample, the present study replicated
      this finding. In addition, different subordinate concepts of MGRS (Physical
      inadequacy, Emotional inexpressiveness, Subordination to women, Intellectual
      inferiority, and Performance failure) predicted Agoraphobic fears, Blood-Injury
      fears, Social fears, and Obsessional checking and washing compulsions
      distinctively. Intellectual inferiority was the strongest predictor of Social
      fears. Most MGRS measures emerged as better predictors of Checking than of
      Washing rituals. There were no sex differences in the predictive capabilities of
      any of the MGRS measures on any of the criterion measures. A hypothetical
      explanation is given for the observation of MGRS being more strongly predictive
      of Checking than of Washing rituals using the concept of "inflated
      responsibility". Implications for assessment, treatment and further studies are
      briefly pinpointed.

PMID- 14972673
TI  - Access to information about harm and safety in spider fearful and nonfearful
      individuals: when they were good they were very very good but when they were bad
      they were horrid.
AB  - This study tests two alternative hypotheses about how phobic information is
      processed in spider fearful and nonfearful individuals: (1) the threat-related
      cognitive set hypothesis and (2) the dimensions hypothesis. Counter to the
      traditional cognitive model of fear, the dimensions hypothesis predicts that
      spider fearful individuals tend to prioritise the harm-safety dimension when
      evaluating animal stimuli, and the consequent stretching of that evaluative
      dimension will confer advantage to the accessing of harm information when
      confronted with phobic stimuli, but conversely safety information when
      encountering FI stimuli. Spider fearful and nonfearful participants generated
      lists of reasons why spiders, fear relevant (e.g. tigers, snakes) and fear
      irrelevant (e.g. rabbits, kittens) animals might be harmful and might be safe.
      The findings indicate that, in comparison to a nonfearful group, spider fearful
      participants have facilitated access to both harm and safety information which is
      context dependent: spider fearful participants were able to generate more reasons
      why spiders may be harmful and fewer why they might be safe than nonfearful
      participants, but conversely were able to generate more reasons why fear
      irrelevant animals might by safe and fewer reasons why they might be harmful than
      the nonfearful group. The implications of these findings for our understanding of
      the cognitive mechanisms underlying fears and phobias are discussed.

PMID- 14972674
TI  - Using the Penn State Worry Questionnaire to identify individuals with generalized
      anxiety disorder: a receiver operating characteristic analysis.
AB  - We report on the use of the Penn State Worry Questionnaire (PSWQ) to identify
      individuals with generalized anxiety disorder (GAD). Fifty individuals with
      primary or secondary GAD and 114 individuals with social anxiety disorder
      (without GAD) completed the PSWQ. In receiver operating characteristic analyses,
      a score of 65 simultaneously optimized sensitivity and specificity in
      discriminating individuals with GAD from individuals with social anxiety
      disorder. Results support the use of the PSWQ in screening individuals likely to
      meet criteria for GAD who present for treatment at an anxiety disorders specialty
      clinic.

PMID- 14972675
TI  - The effects of acceptance versus control contexts on avoidance of panic-related
      symptoms.
AB  - The present study compared the effects of creating an acceptance versus a control
      treatment context on the avoidance of aversive interoceptive stimulation. Sixty
      high anxiety sensitive females were exposed to two 10-min periods of 10% carbon
      dioxide enriched air, an anxiogenic stimulus. Before each inhalation period,
      participants underwent a training procedure aimed at encouraging them either to
      mindfully observe (acceptance context) or to control symptoms via diaphragmatic
      breathing (control context). A third group was given no particular training or
      instructions. We hypothesized that an acceptance rather than control context
      would be more useful in the reduction of anxious avoidance. Compared to control
      context and no-instruction participants, acceptance context participants were
      less avoidant behaviorally and reported less intense fear and cognitive symptoms
      and fewer catastrophic thoughts during the CO(2) inhalations. We discuss the
      implications of our findings for an acceptance-focused vs. control-focused
      context when conducting clinical interventions for panic and other anxiety
      disorders.

PMID- 14972676
TI  - Examining the inventory of interpersonal problems as a tool for conducting
      analogue studies of mechanisms underlying Borderline Personality Disorder.
AB  - Despite recent advancements in the treatment of Borderline Personality Disorder
      (BPD), little is known about the underlying mechanisms in the development and
      maintenance of the disorder. To examine these issues, it is first necessary to
      identify a brief screening measure that can be used to assess factors underlying
      BPD. Considering this need, the current investigation examined the utility of a
      BPD-related composite consisting of the Inventory of Interpersonal Problems
      Interpersonal Sensitivity (IIP-IS) and Aggression (IIP-Ag) subscales of the IIP
      in a sample of college students ( [Formula: see text] ) and a sample of
      individuals seeking residential drug use treatment ( [Formula: see text] ). Data
      indicated that score on this composite measure (IIP-BPD) was positively related
      to scores on measures tapping BPD-related symptomotology, as well or better than
      the IIP total score in all cases. These data suggest the specificity of the IIP
      BPD and support its use in analogue studies to better understand the mechanisms
      underlying the disorder.

PMID- 14972677
TI  - radish encodes a phospholipase-A2 and defines a neural circuit involved in
      anesthesia-resistant memory.
AB  - BACKGROUND: In both vertebrate and invertebrate animals, anesthetic agents cause
      retrograde amnesia for recently experienced events. In contrast, older memories
      are resistant to the same treatments. In Drosophila, anesthesia-resistant memory
      (ARM) and long-term memory (LTM) are genetically distinct forms of long-lasting
      memory that exist in parallel for at least a day after training. ARM is disrupted
      in radish mutants but is normal in transgenic flies overexpressing a CREB
      repressor transgene. In contrast, LTM is normal in radish mutants but is
      disrupted in CREB repressor transgenic flies. To date, nothing is known about the
      molecular, genetic, or cell biological pathways underlying ARM. RESULTS: Here, we
      report the molecular identification of radish as a phospholipase-A2, providing
      the first clue about signaling pathways underlying ARM in any animal. An enhancer
      trap allele of radish (C133) reveals expression in a novel anatomical pathway.
      Transgenic expression of PLA2 under control of C133 restores normal levels of ARM
      to radish mutants, whereas transient disruption of neural activity in C133
      neurons inhibits memory retention. Notably, expression of C133 is not in mushroom
      bodies, the primary anatomical focus of olfactory memory research in Drosophila.
      CONCLUSIONS: Identification of radish as a phospholipase-A2 and the neural
      expression pattern of an enhancer-trap allele significantly broaden our
      understanding of the biochemistry and anatomy underlying olfactory memory in
      Drosophila.

PMID- 14972678
TI  - Aurora B phosphorylates centromeric MCAK and regulates its localization and
      microtubule depolymerization activity.
AB  - BACKGROUND: Sister kinetochores must bind microtubules in a bipolar fashion to
      equally segregate chromosomes during mitosis. The molecular mechanisms underlying
      this process remain unclear. Aurora B likely promotes chromosome biorientation by
      regulating kinetochore-microtubule attachments. MCAK (mitotic centromere
      associated kinesin) is a Kin I kinesin that can depolymerize microtubules. These
      two proteins both localize to mitotic centromeres and have overlapping mitotic
      functions, including regulation of microtubule dynamics, proper chromosome
      congression, and correction of improper kinetochore-microtubule attachments.
      RESULTS: We show that Aurora B phosphorylates and regulates MCAK both in vitro
      and in vivo. Specifically, we mapped six Aurora B phosphorylation sites on MCAK
      in both the centromere-targeting domain and the neck region. Aurora B activity
      was required to localize MCAK to centromeres, but not to spindle poles. Aurora B
      phosphorylation of serine 196 in the neck region of MCAK inhibited its
      microtubule depolymerization activity. We found that this key site was
      phosphorylated at centromeres and anaphase spindle midzones in vivo. However,
      within the inner centromere there were pockets of both phosphorylated and
      unphosphorylated MCAK protein, suggesting that phosphate turnover is crucial in
      the regulation of MCAK activity. Addition of alpha-p-S196 antibodies to Xenopus
      egg extracts or injection of alpha-p-S196 antibodies into cells caused defects in
      chromosome positioning and/or segregation. CONCLUSIONS: We have established a
      direct link between the microtubule depolymerase MCAK and Aurora B kinase. Our
      data suggest that Aurora B both positively and negatively regulates MCAK during
      mitosis. We propose that Aurora B biorients chromosomes by directing MCAK to
      depolymerize incorrectly oriented kinetochore microtubules.

PMID- 14972679
TI  - Two fission yeast homologs of Drosophila Mei-S332 are required for chromosome
      segregation during meiosis I and II.
AB  - BACKGROUND: Meiosis produces haploid gametes from diploid progenitor cells. This
      reduction is achieved by two successive nuclear divisions after one round of DNA
      replication. Correct chromosome segregation during the first division depends on
      sister kinetochores being oriented toward the same spindle pole while homologous
      kinetochores must face opposite poles. Segregation during the second division
      depends on retention of sister chromatid cohesion between centromeres until the
      onset of anaphase II, which in Drosophila melanogaster depends on a protein
      called Mei-S332 that binds to centromeres. RESULTS: We report the identification
      of two homologs of Mei-S332 in fission yeast using a knockout screen. Together
      with their fly ortholog they define a protein family conserved from fungi to
      mammals. The two identified genes, sgo1 and sgo2, are required for retention of
      sister centromere cohesion between meiotic divisions and kinetochore orientation
      during meiosis I, respectively. The amount of meiotic cohesin's Rec8 subunit
      retained at centromeres after meiosis I is reduced in Deltasgo1, but not in
      Deltasgo2, cells, and Sgo1 appears to regulate cleavage of Rec8 by separase. Both
      Sgo1 and Sgo2 proteins localize to centromere regions. The abundance of Sgo1
      protein normally declines after the first meiotic division, but extending its
      expression by altering its 3'UTR sequences does not greatly affect meiosis II.
      Its mere presence within the cell might therefore be insufficient to protect
      centromeric cohesion. CONCLUSIONS: A conserved protein family based on Mei-S332
      has been identified. The two fission yeast homologs are implicated in meiosis I
      kinetochore orientation and retention of centromeric sister chromatid cohesion
      until meiosis II.

PMID- 14972680
TI  - The spinocerebellar ataxia 8 noncoding RNA causes neurodegeneration and
      associates with staufen in Drosophila.
AB  - Spinocerebellar Ataxia 8 (SCA8) appears unique among triplet repeat expansion
      induced neurodegenerative diseases because the predicted gene product is a
      noncoding RNA. Little is currently known about the normal function of SCA8 in
      neuronal survival or how repeat expansion contributes to neurodegeneration. To
      investigate the molecular context in which SCA8 operates, we have expressed the
      human SCA8 noncoding RNA in Drosophila. SCA8 induces late-onset, progressive
      neurodegeneration in the Drosophila retina. Using this neurodegenerative
      phenotype as a sensitized background for a genetic modifier screen, we have
      identified mutations in four genes: staufen, muscle-blind, split ends, and
      CG3249. All four encode neuronally expressed RNA binding proteins conserved in
      Drosophila and humans. Although expression of both wild-type and repeat-expanded
      SCA8 induce neurodegeneration, the strength of interaction with certain modifiers
      differs between the two SCA8 backgrounds, suggesting that CUG expansions alter
      associations with specific RNA binding proteins. Our demonstration that SCA8 can
      recruit Staufen and that the interaction domain maps to the portion of the SCA8
      RNA that undergoes repeat expansion in the human disease suggests a specific
      mechanism for SCA8 function and disease. Genetic modifiers identified in our SCA8
      based screens may provide candidates for designing therapeutic interventions to
      treat this disease.

PMID- 14972681
TI  - Rho-LIM kinase signaling regulates ecdysone-induced gene expression and
      morphogenesis during Drosophila metamorphosis.
AB  - The steroid hormone 20-hydroxyecdysone (ecdysone) is the key regulator of
      postembryonic developmental transitions in insects and controls metamorphosis by
      triggering the morphogenesis of adult tissues from larvae. The Rho GTPase, which
      mediates cell shape change and migration, is also an essential regulator of
      tissue morphogenesis during development. Rho activity can modulate gene
      expression, in part, by activating LIM kinase (LIMK) and consequently affecting
      actin-induced SRF transcriptional activity. We have established a link between
      Rho-LIMK-SRF signaling and the ecdysone-induced transcriptional response during
      Drosophila development. Specifically, we determined that the Rho GTPase, via
      LIMK, regulates the expression of several ecdysone-responsive genes, including
      those encoding the ecdysone receptor itself, a downstream transcription factor
      (Br-C), and Stubble, a transmembrane protease required for proper leg formation.
      Stubble and Br-C mutants exhibit strong genetic interactions with several Rho
      pathway components in the formation of adult structures, but not with Rac or
      Cdc42. In cultured SL2 cells, inhibition of Rho, F-actin assembly, or SRF blocks
      the transcriptional response to ecdysone. Together, these findings indicate a
      link between Rho-LIMK signaling and steroid hormone-induced gene expression in
      the context of metamorphosis and thereby establish a novel role for the Rho
      GTPase in development.

PMID- 14972682
TI  - Nanos and Pumilio are essential for dendrite morphogenesis in Drosophila
      peripheral neurons.
AB  - Much attention has focused on dendritic translational regulation of neuronal
      signaling and plasticity. For example, long-term memory in adult Drosophila
      requires Pumilio (Pum), an RNA binding protein that interacts with the RNA
      binding protein Nanos (Nos) to form a localized translation repression complex
      essential for anterior-posterior body patterning in early embryogenesis. Whether
      dendrite morphogenesis requires similar translational regulation is unknown. Here
      we report that nos and pum control the elaboration of high-order dendritic
      branches of class III and IV, but not class I and II, dendritic arborization (da)
      neurons. Analogous to their function in body patterning, nos and pum require each
      other to control dendrite morphogenesis, a process likely to involve
      translational regulation of nos itself. The control of dendrite morphogenesis by
      Nos/Pum, however, does not require hunchback, which is essential for body
      patterning. Interestingly, Nos protein is localized to RNA granules in the
      dendrites of da neurons, raising the possibility that the Nos/Pum translation
      repression complex operates in dendrites. This work serves as an entry point for
      future studies of dendritic translational control of dendrite morphogenesis.

PMID- 14972683
TI  - Training improves acoustic pattern perception.
AB  - Pitch changes that occur in speech and melodies can be described in terms of
      contour patterns of rises and falls in pitch and the actual pitches at each point
      in time. This study investigates whether training can improve the perception of
      these different features. One group of ten adults trained on a pitch-contour
      discrimination task, a second group trained on an actual-pitch discrimination
      task, and a third group trained on a contour comparison task between pitch
      sequences and their visual analogs. A fourth group did not undergo training. It
      was found that training on pitch sequence comparison tasks gave rise to
      improvements in pitch-contour perception. This occurred irrespective of whether
      the training task required the discrimination of contour patterns or the actual
      pitch details. In contrast, none of the training tasks were found to improve the
      perception of the actual pitches in a sequence. The results support psychological
      models of pitch processing where contour processing is an initial step before
      actual pitch details are analyzed. Further studies are required to determine
      whether pitch-contour training is effective in improving speech and melody
      perception.

PMID- 14972684
TI  - Wlds-mediated protection of dopaminergic fibers in an animal model of Parkinson
      disease.
AB  - Parkinson disease (PD) is characterized by the progressive degeneration of
      substantia nigra dopaminergic neurons projecting to the striatum. Since the
      deficit in striatal dopamine is the main cause of PD symptoms, it appears
      critical to preserve axon terminals. Significant axon protection from peripheral
      nerve Wallerian degeneration is observed in Wlds mice, a phenotype conferred by a
      spontaneous dominant mutation. To assess any Wlds-mediated rescue of dopamine
      fibers in a PD model, the nigrostriatal pathway of Wlds mice was lesioned with 6
      hydroxydopamine (6-OHDA), a catecholaminergic neurotoxin. Following 6-OHDA
      injection in the medial forebrain bundle, Wlds mice showed remarkable dopamine
      fiber protection in the striatum. Drug-induced rotational behavior confirmed the
      nigrostriatal fiber ability to release dopamine, although revealing an abnormal
      neurotransmitter control presumably due to disrupted axonal transport. Following
      6-OHDA injection in the midstriatum, only a protection trend was observed.
      Strikingly, no protection of Wlds nigral dopaminergic cell bodies was obtained
      following either nigrostriatal lesion. Besides showing subtle differences in the
      degeneration process between subcellular compartments, the reported Wlds-mediated
      protection of the dopamine axon terminals in an animal model of PD may lead to
      the understanding of mechanisms underlying axon loss and to the development of
      new therapeutic approaches.

PMID- 14972685
TI  - Eye position affects orienting of visuospatial attention.
AB  - The ability to detect an incoming visual stimulus is enhanced by knowledge of
      stimulus location (orienting of visuospatial attention). Although the brain
      mechanisms at the basis of this enhancement are not yet fully clarified, there is
      evidence that orienting of attention is accompanied by the activation of
      oculomotor circuits. It remains unclear, however, whether this oculomotor
      activity is an epiphenomenon or is functionally related to the attentional
      process. Attentional benefits are usually measured by the classical Posner
      paradigm. When subjects fixate centrally and are requested to detect a visual
      stimulus that could appear in an attended or unattended location, they react
      faster to stimuli appearing in the attended one. Here, we demonstrate that in
      monocular vision visuospatial attention was significantly modulated by the
      position of the eye in the orbit. When the screen was placed 40 degrees to the
      right or to the left of subjects' sagittal plane, attentional benefits for
      stimuli appearing in subjects' temporal spatial hemifield dramatically decayed,
      even if the retinal stimulation was exactly the same as in the classical
      paradigm. The finding that eyes and attention show a common limit stop point
      supports their close functional coupling.

PMID- 14972686
TI  - Molecular characterization of the long-day response in the Soay sheep, a seasonal
      mammal.
AB  - In mammals, seasonal timekeeping depends on the generation of a nocturnal
      melatonin signal that reflects nightlength/daylength. To understand the
      mechanisms by which the melatonin signal is decoded, we studied the photoperiodic
      control of prolactin secretion in Soay sheep, which is mediated via melatonin
      responsive cells in the pars tuberalis of the pituitary. We demonstrate that the
      phases of peak expression of the clock genes Cryptochrome1 (Cry1), Period1
      (Per1), and RevErbalpha respond acutely to altered melatonin secretion after a
      switch from short to long days. Cry1 is activated by melatonin onset, forming the
      dusk component of the molecular decoder, while Per1 expression at dawn reflects
      the offset of melatonin secretion. The Cry1-Per1 interval immediately adjusts to
      the melatonin signal on the first long day, and this is followed within 24 hr by
      an increase in prolactin secretion. The timing of peak RevErbalpha expression
      also responds to a switch to long days due to altered melatonin secretion but
      does not immediately reset to an entrained long-day state. These data suggest
      that effects of melatonin on clock gene expression are pivotal events in the
      neuroendocrine response and that pars tuberalis cells can act as molecular
      calendars, carrying a form of "photoperiodic memory."

PMID- 14972687
TI  - Sumo1 conjugates mitochondrial substrates and participates in mitochondrial
      fission.
AB  - Mitochondrial fission requires the evolutionarily conserved dynamin related
      protein (DRP1), which is recruited from the cytosol to the mitochondrial outer
      membrane to coordinate membrane scission. Currently, the mechanism of recruitment
      and assembly of DRP1 on the mitochondria is unclear. Here, we identify Ubc9 and
      Sumo1 as specific DRP1-interacting proteins and demonstrate that DRP1 is a Sumo1
      substrate. In addition, a surprising number of Sumo1 conjugates were observed in
      the mitochondrial fractions, suggesting that sumoylation is a common
      mitochondrial modification. Video microscopy demonstrates that YFP:Sumo1 is often
      found at the site of mitochondrial fission and remains tightly associated to the
      tips of fragmented mitochondria. Consistent with this, fluorescence microscopy
      revealed that a portion of total cytosolic YFP:Sumo1 colocalizes with endogenous
      mitochondrial DRP1. Finally, transient transfection of Sumo1 dramatically
      increases the level of mitochondrial fragmentation. Analysis of endogenous DRP1
      levels indicates that overexpression of Sumo1 specifically protects DRP1 from
      degradation, resulting in a more stable, active pool of DRP1, which at least
      partially accounts for the excess fragmentation. Together, these data are the
      first to identify a function for Sumo1 on the mitochondria and suggest a novel
      role for the participation of Sumo1 in mitochondrial fission.

PMID- 14972688
TI  - The nuclear dsRNA binding protein HYL1 is required for microRNA accumulation and
      plant development, but not posttranscriptional transgene silencing.
AB  - MicroRNAs (miRNAs) are 21-24 nucleotides long molecules processed from imperfect
      double-stranded RNAs (dsRNAs). They regulate gene expression by targeting
      complementary mRNA for cleavage or interfering with their translation. In
      Arabidopsis, point mutations in or short truncations of the nuclear DICER-LIKE1
      (DCL1) or HEN1 protein reduce miRNA accumulation and increase uncleaved target
      mRNAs accumulation, resulting in developmental abnormalities. Here, we show that
      miRNA accumulation also depends on the activity of HYL1, a nuclear dsRNA binding
      protein. hyl1 mutants exhibit developmental defects overlapping with that of dcl1
      and hen1 mutants, suggesting that DCL1, HEN1, and HYL1 act together in the
      nucleus. We validate additional target mRNAs and show that reduced miRNA
      accumulation in hyl1 correlates with an increased accumulation of uncleaved
      target mRNAs, including meristem- and auxin-related genes, providing clues for
      the developmental abnormalities of hyl1 and for the previous identification of
      hyl1 as a mutant with altered responses to phytohormones. Lastly, we show that
      posttranscriptional transgene silencing occurs in hyl1, suggesting that HYL1 has
      specialized function in the plant miRNA pathway, whereas the HYL1-related RDE-4
      and R2D2 proteins associate with DICER in the cytoplasm and act in the RNAi
      pathway in C. elegans and Drosophila, respectively.

PMID- 14972689
TI  - Deficient acquisition and consolidation: intertrial free recall performance in
      Alzheimer's disease and mild cognitive impairment.
AB  - Abstract Previous research demonstrates that dementia of the Alzheimer type (DAT)
      is characterised by deficits of episodic memory, especially in the acquisition of
      new material. As well as this deficit in acquisition, some researchers have also
      argued for a deficit in consolidation in DAT. We examined acquisition and
      consolidation by measuring the intertrial gained and lost access in DAT, Mild
      Cognitive Impairment (MCI) and controls. We report findings from a study of
      clinical data based on assessment of patients using three free recall trials of a
      word list. We found that both DAT and MCI groups showed a deficit in acquisition
      and consolidation of items between trials relative to controls. Moreover, the DAT
      group was significantly impaired relative to the MCI group for both acquisition
      and consolidation. Correlations within each group showed that there were strong
      relationships between intertrial measures and standard measures of memory
      function. Importantly in no group was there a significant correlation between our
      measures of acquisition and consolidation: we argue that these measures reflect
      different underlying processes, and the failure to consolidate in DATand MCI is
      not related to the deficit in acquisition. Finally, we showed strong correlations
      between our measure and dementia severity, suggesting that acquisition and
      consolidation both get worse as the dementia progresses.

PMID- 14972690
TI  - Visual processing impairments and decrements in regional brain activity in
      Alzheimer's disease.
AB  - The relationships between intermediate visual processes, involving object and
      space perception, and regional brain activity using positron emission tomography
      and single photon emission tomography were investigated in 16 patients with
      Alzheimer's disease. Significant region specific correlations were found between
      unfamiliar face matching and cerebral activity in the left occipito-temporal
      region and middle/inferior temporal regions bilaterally. Letter-word
      identification correlated significantly with brain activity in the angular gyri
      and occipital association cortices bilaterally, as well as a broad region of
      activation in the left hemisphere temporal, parietal and occipital lobes.
      Additionally, a significant correlation was found between ratings of performance
      of instrumental activities of daily living and brain activity in occipito
      temporal and middle/inferior temporal regions. The present study demonstrates
      that the neuropathological distribution typically seen in Alzheimer's disease
      corresponds to impairments in specific aspects of intermediate visual perceptual
      processing, and it is related to the daily living skills of patients with
      Alzheimer's disease.

PMID- 14972691
TI  - Global-local visual biases correspond with visual-spatial orientation.
AB  - Within the past decade, numerous investigations have demonstrated reliable
      associations of global-local visual processing biases with right and left
      hemisphere function, respectively (cf. Van Kleeck, 1989). Yet the relevance of
      these biases to other cognitive functions is not well understood. Towards this
      end, the present research examined the relationship between global-local visual
      biases and perception of visual-spatial orientation. Twenty-six women and 23 men
      completed a global-local judgment task (Kimchi and Palmer, 1982) and the Judgment
      of Line Orientation Test (JLO; Benton, Sivan, Hamsher, Varney, and Spreen, 1994),
      a measure of visual-spatial orientation. As expected, men had better performance
      on JLO. Extending previous findings, global biases were related to better visual
      spatial acuity on JLO. The findings suggest that global-local biases and visual
      spatial orientation may share underlying cerebral mechanisms. Implications of
      these findings for other visually mediated cognitive outcomes are discussed.

PMID- 14972692
TI  - Digit span in dyslexia: variations according to language comprehension and
      mathematics skills.
AB  - The aim of this study was to investigate digit span performance in dyslexia. It
      was hypothesised that differences would be found in accordance with subgrouping
      by language comprehension and mathematic skills, and by analyses of how the digit
      span scores were attained. Two digit span tasks were given to a group of dyslexic
      children and controls (n = 57), mean age 12.62 (SD = 1.43). The tasks were "Digit
      Span" of the WISC-R, and "Digit Span 2," where the use of back-up strategies like
      finger counting and lip reading were restricted. As expected, the digit span
      scores were significantly lower in the dyslexia group than in the control group.
      Restrictions of back-up strategies did not alter the scores in the control group,
      while the scores were lowered in the dyslexia group. Further analyses of longest
      digit span, serial recall, and serial position indicated different retrieval
      patterns in the subgroups. The subgroup with good language comprehension and
      mathematic skills (n = 12), showed impaired serial recall especially in backward
      recall. The subgroup with good language comprehension skills, but with
      mathematics impairment (n = 9), showed impaired serial recall in both forward and
      backward recall. The subgroup with language impairments (n = 16), recalled fewer
      digits than the two other subgroups. The findings were discussed in relation to
      the "Phonological loop" of the Multi Component Model of Working Memory, and
      implications for intervention were discussed.

PMID- 14972693
TI  - Neurobehavioral functioning in obstructive sleep apnea: differential effects of
      sleep quality, hypoxemia and subjective sleepiness.
AB  - This study evaluated the relationship between neuropsychological and affective
      functioning, subjective sleepiness and sleep-disordered breathing in 100 patients
      with obstructive sleep apnea (OSA). Using principal components analysis, three
      indices of sleep-disordered breathing were identified from polysomnography: sleep
      disturbance, extent of nocturnal hypoxemia, and sleep quality. Poorer sleep
      quality was related to slower processing speed, somatic symptomatology and
      tension-anxiety levels. Nocturnal hypoxemia was related to visuconstructional
      abilities, processing speed and mental flexibility. Patients who had high levels
      of subjective sleepiness had poorer performances on a complex task of executive
      functioning and higher levels of tension-anxiety. These results imply a
      differential effect of sleep-disordered breathing on domains of
      neuropsychological functioning. Additionally, they suggest that a patient's
      subjective level of sleepiness is a good predictor of certain aspects of
      neurobehavioral functioning.

PMID- 14972694
TI  - Visual p300 effects beyond symptoms in concussed college athletes.
AB  - In order to assess whether cerebral anomalies may be observed in the absence of
      clinical symptoms, the current study compared the effects of concussions on
      attentional capacities (reaction times, accuracy) and Event-Related Potentials
      (ERPs) in concussed athletes with (n = 10) or without (n = 10) symptoms as well
      as in athletes who never had a concussion (n = 10). The P300 response was
      recorded from 28 electrodes during a modified visual oddball paradigm.
      Participants were instructed to press a key upon the appearance of the frequent
      stimuli as well as when a rare nontarget stimulus followed the frequent one. The
      other key was to be pressed when the subsequent rare stimuli (rare target)
      appeared until a frequent one reappeared. The symptomatic athletes displayed
      longer reaction times than the other two groups of athletes. The P300 amplitude
      to the rare target stimuli was significantly more attenuated in the symptomatic
      athletes than in the other two groups. Moreover, the P300 amplitude varied
      inversely with the severity of post-concussion symptoms but was not influenced by
      time elapsed since injury. Although the clinical significance of the P300
      differences shown by the symptomatic athletes is still uncertain, the results do
      indicate that symptom severity may be a crucial indicator of functional
      impairments following mild traumatic brain injury.

PMID- 14972695
TI  - Event-rate manipulation and its effect on arousal modulation and response
      inhibition in adults with high functioning autism.
AB  - The aim of the current study was to evaluate arousal modulation and response
      inhibition in adults with high functioning autism (HFA). Using a go/no-go
      paradigm with varying presentation rate, it was found that performance efficiency
      (Mean RT, Standard Deviation of RT and Errors of Commission) in adults with HFA
      was the same as in the control group in the condition with a slow (6 s) and
      medium (2 s) presentation rate, but that it decreased in the condition with a
      fast presentation rate (1 s): many errors of commission were made in this
      condition. Findings were interpreted in terms of an arousal modulation deficiency
      that interfered with the capacity to inhibit responses in HFA.

PMID- 14972696
TI  - Dichotic listening in children with focal epilepsy: effects of structural brain
      abnormality and seizure characteristics.
AB  - The study examined performance on a dichotic listening test in children with
      focal epilepsy. The aim of the study was to explore how factors related to brain
      pathology would affect ear advantage. The effects of lateralization of
      epileptogenic area, size and localization of structural abnormality on MRI
      findings, and seizure characteristics were studied. Children treated for focal
      epileptic seizures took part in the study (N = 35). The dichotic test consisted
      of pairs of words, nonwords, syllables and vowels. Results demonstrated that
      large congenital structural abnormality in the left hemisphere altered ear
      advantage whereas smaller abnormality and right-hemisphere abnormality did not.
      Further, epileptic seizures of left-hemisphere origin that had started at an
      early age affected ear advantage whereas seizure frequency at the time of the
      assessment did not. Children with early onset of seizures of right-hemisphere
      origin had a strong right-ear advantage. The total score did not differ between
      the groups. There was a strong negative correlation between the scores for the
      right-ear and the left-ear. The findings were interpreted to indicate altered
      functional dominance for perception of auditory, linguistic stimuli following
      early left-hemisphere pathology rather than unilateral functional suppression.

PMID- 14972697
TI  - Backpropagation and regression: comparative utility for neuropsychologists.
AB  - The aim of this research was to compare the data analytic applicability of a
      backpropagated neural network with that of regression analysis. Thirty
      individuals between the ages of 64 and 86 (Mean age = 73.6; Mean years education
      = 15.4; % women = 50) participated in a study designed to validate a new test of
      spatial ability administered in virtual reality. As part of this project a
      standard neuropsychological battery was administered. Results from the multiple
      regression model R(2) = .21, p < .28; Standard Error = 18.01) were compared with
      those of a backpropagated ANN (R(2) = .39, p < .02; Standard Error = 13.07). This
      18% increase in prediction of a common neuropsychological problem demonstrated
      that an ANN has the potential to outperform a regression.

PMID- 14972698
TI  - A new approach in clinical neuropsychology to the assessment of spatial working
      memory: the block suppression test.
AB  - The Block Suppression Paradigm developed by Beblo, Klaver, Grubich, Wachowius,
      and Herrmann (1999) is based on the Corsi Block tapping test and requires that a
      subject reproduces every 2nd block in a given sequence. Results from two studies
      of a standardized version, the Block Suppression Test (BST), are presented here.
      In Study 1 the BST was administered to 48 healthy subjects along with a battery
      of comprehensive neuropsychological tests. The reliability of the BST proved
      satisfactory under psychometric analysis, while Principal Component Analysis
      (PCA) confirmed its validity. In Study 2 the BST was administered to a clinical
      sample of 31 brain-damaged patients to demonstrate its clinical practicability.

PMID- 14972699
TI  - Detecting incomplete effort on the MMPI-2: an examination of the Fake-Bad Scale
      in mild head injury.
AB  - The current study is an investigation of the MMPI-2 Fake Bad Scale ( FBS ) in the
      detection of incomplete effort in mild head injury (MHI). Using ROC curve
      analysis, we found that a cutoff score of 21 had a sensitivity of 90% and
      specificity of 90%, providing an overall correct classificatory rate of 90%. In
      addition, traditional indices of faking bad on the MMPI-2, the F and F-K indices,
      fared relatively poorly by comparison and added no predictive power over the FBS.
      Finally, multivariate analyses revealed that although the FBS shares a number of
      items with Hs and Hy scales, the FBS carried the majority of variance in
      predicting incomplete effort in our MHI sample. Overall, these findings indicate
      that the FBS has high sensitivity and specificity in identifying incomplete
      effort in mild head injury.

PMID- 14972700
TI  - Detecting poor effort and malingering with an expanded version of the Auditory
      Verbal Learning Test (AVLTX): validation with clinical samples.
AB  - Three studies describe the development and validation of a new procedure (AVLTX)
      to detect inadequate effort or malingering by adding 60-min delayed
      recall/recognition trials and identifying "impaired" memory performances that are
      highly inconsistent with performances of brain-damaged (BD) individuals. In Study
      I, AVLTX performances of 25 probable malingerers (PMs) were compared with those
      of 43BD and 40 psychiatric patients (PSYs). Seven inconsistencies were identified
      and converted to scaled inconsistency scores, yielding the exaggeration index
      (EI). Study II reported cross-validation in an independent sample of 34 PM, 70BD
      and 89 PSY, showing sensitivity of 0.59 and specificities of 0.97 (BD) and 0.92
      (PSY). Study III compared the diagnostic accuracy of the EI with two well
      established effort assessment paradigms, exemplified by the RMTand DRT (a symptom
      validity test). The RMT showed excellent sensitivity and poor specificity; the
      DRT showed poor sensitivity and excellent specificity; the EI showed good
      sensitivity and excellent specificity. Adding a second delayed trial to list
      learning tests can be a time-efficient procedure to detect inadequate effort.

PMID- 14972701
TI  - Performance differences between adult heterosexual and homosexual men on the
      Digit-Symbol Substitution subtest of the WAIS-R.
AB  - Previous evidence suggests that sexual orientation influences performance on a
      number of cognitive functions known to be sexually dimorphic. This investigation
      examined the performance of 240 right-handed subjects (60 heterosexual men, 60
      homosexual men, 60 heterosexual women and 60 homosexual women) on one of the most
      commonly used neuropsychological tests to show normative sex differences, the
      Digit-Symbol Substitution test of the WAIS-R. Analysis of scaled Digit-Symbol
      scores revealed that heterosexual women and homosexual men outperformed
      heterosexual men. The magnitude of these differences were modest by standard
      criteria. No differences were found between heterosexual and homosexual women.
      The findings implicate within-sex variation in one test that relies on intact
      executive function.

PMID- 14972703
TI  - Performance of girls with ADHD and comparison girls on the Rey-Osterrieth Complex
      Figure: evidence for executive processing deficits.
AB  - In spite of a multitude of scoring approaches, the ability of the Rey-Osterrieth
      Complex Figure (ROCF) to measure executive functions versus grapho-motor skill is
      still open to question. To clarify this issue, we examined the performance of an
      ethnically and socioeconomically diverse sample of preadolescent girls (ADHD
      Combined, n = 93; ADHD-Inattentive, n = 47; and comparison girls, n = 88) on the
      ROCF, scoring both immediate copy and delayed recall performance. Girls with ADHD
      performed the task following a stimulant medication washout. Dependent measures
      were the established Developmental Scoring System variables of Organization,
      Accuracy, and Style, plus an operationalized and extensively detailed scoring of
      errors, featuring an error proportion score (EPS). The major finding is that only
      EPS differentiated girls with ADHD from comparison girls (a) on both immediate
      and delayed performance and (b) with stringent statistical control of Performance
      IQ, fine motor speed, and performance on the Porteus Mazes (as well as
      comorbidities), with effect sizes in the medium range. Perseverative errors
      contributed significantly to EPS. Overall, error scores on the ROCF appear to tap
      planning, a key executive function, and are quite sensitive to deficits in this
      domain for girls with ADHD.

PMID- 14972704
TI  - Relations between inhibition, executive functioning, and ADHD symptoms: a
      longitudinal study from age 5 to 8(1/2) years.
AB  - The present study examined whether inhibition measured as early as preschool can
      predict more general executive functioning and ADHD symptoms at school age. In
      contrast to previous studies, the present study focused specifically on ADHD
      symptoms rather than general disruptive behavior problems, and boys and girls
      were studied separately. The main result was that inhibition was strongly related
      to ADHD symptoms both in school and at home for boys, but only in the school
      context for girls. Early inhibition was also significantly related to later
      executive functioning, and concurrent relations were found between executive
      functioning and ADHD symptoms, although in both cases only for boys. Besides
      this, inhibition added significantly to the variance, beyond that of executive
      functioning, which meant that for boys, inhibition and the other executive
      functioning explained about half the variance in inattention problems. The
      stronger relation between inhibition, executive functioning and ADHD symptoms for
      boys compared to girls could suggests that either the predictors of ADHD are
      different for the two sexes, or girls are more often equipped with some factor
      that protects them from developing ADHD symptoms, despite poor executive
      functioning. However, it is also possible that relations are just harder to
      demonstrate for girls due to their lower incidence of disruptive problem
      behaviors.

PMID- 14972705
TI  - Concurrent and 2-year longitudinal relations between executive function and the
      behavior of 1st and 2nd grade children.
AB  - Abstract Concurrent and 2-year longitudinal relations were investigated between
      two indicators of children's ( n =60; mean age = years 11 months) executive
      function, inhibitory control and sequencing ability, and behavior problem
      symptomatology. Dependent measures were parent and teacher reported internalizing
      and externalizing behavior. Hierarchical multiple regression analyses
      demonstrated few significant concurrent associations between either inhibitory
      control or sequencing ability, and behavior problem symptoms. In contrast,
      baseline inhibitory control predicted decreased teacher reported externalizing,
      and parent reported externalizing and internalizing behavior problems over a 2
      year period. Baseline sequencing ability also predicted decreased teacher
      reported externalizing and parent reported internalizing behavior over this same
      time period. Results suggest that some aspects of executive function in early
      elementary grade-school children may be more strongly associated with change in
      behavior over time than concurrent behavior. Implications of these findings for
      the prevention of behavior problems are discussed.

PMID- 14972706
TI  - The role of dichotic listening performance and tasks of executive functions in
      reading impairment: a discriminant function analysis.
AB  - This study focused on the role of dichotic listening performance for the
      identification of reading impaired subtypes. Dichotic listening (DL), using
      verbal stimuli, has shown to be a valid measure of language lateralization.
      Usually, lateralization is estimated from the proportion of right ear over left
      ear accuracy during a free recall test procedure. However, it has been suggested
      that a more accurate estimate of laterality can be obtained by using a directed
      attention procedure. A sample of 43 reading disabled children of whom 18 showed
      signs of impaired language comprehension skills and 25 without language
      comprehension impairments, were compared to 20 age, and gender, matched controls
      on dichotic listening performance in both an unbiased free recall task and in a
      directed attention task using consonant-vowel syllables as dichotic stimuli. A
      laterality index was calculated for left and right ear stimuli reported during
      both the free recall condition and the attended ear-scores for the two directed
      attention conditions. Although both DL procedures yielded significant group
      differences, with a lower laterality score for the reading disabled compared to
      the controls, there was no main effect of DL-procedure or group x procedure
      interaction. Taken alone, DL performance could correctly classify 42% of the
      reading impaired samples, but together with other measures of executive
      functions, discriminant function analyses yielded 90.74% accuracy in classifying
      reading impaired children. The result indicates that DL together with tests of
      executive functions are valuable tools for assessment of reading impaired
      subjects.

PMID- 14972707
TI  - Inner and outer face perception in children with autism.
AB  - Possible peculiarities in face perception in the autistic population were
      explored through two experiments. Fourteen autistic children (mean age=10 years 1
      month) were individually matched to verbal mental age (VMA) and chronological age
      (CA) subjects. In a first experiment, subjects were to match faces on the basis
      of either their outer (hair, chin, ears) or their inner (eyes, nose, mouth)
      aspects. Autistic children performed equally well in both conditions, while VMA
      matched children performed better in the outer than the inner part condition. In
      a second experiment, chimeric faces consisting of the outer part of an
      individual's face and the inner part of another individual's face were presented
      to the subjects. None of the groups showed a preference for neither the outer nor
      the inner part of the face in this condition. Results were discussed in terms of
      the existence of a local visual processing strategy in this population.

PMID- 14972713
TI  - Ocular disposition of novel lipophilic diester prodrugs of ganciclovir following
      intravitreal administration using microdialysis.
AB  - PURPOSE: The objective of the present study was to explore acyl diester prodrugs
      (acetate, propionate, and butyrate) of ganciclovir (GCV) to achieve sustained
      therapeutic concentrations of GCV in the vitreous over a prolonged period of time
      following intravitreal administration. METHODS: Male New Zealand albino rabbits
      (2-2.5 kg) were used for these studies. Animals were kept under anesthesia
      throughout the course of an experiment using ketamine HCl and xylazine. A
      concentric microdialysis probe was implanted into the vitreous chamber with a 21
      gauge needle and a linear microdialysis probe was inserted into the anterior
      chamber across the cornea using a 25-gauge needle. The probes were perfused with
      isotonic phosphate buffer saline (pH 7.4) at a flow rate of 2 microl/min. GCV
      prodrugs (33.2 microg of diacetate, 35.9 microg dipropionate prodrugs, and 9.87
      microg of dibutyrate prodrug) or GCV (50, 25, and 12.5 microg) were administered
      intravitreally and the microdialysis samples were collected every 20 minutes over
      a period of 10 hours. RESULTS: Vitreal terminal elimination half-life of GCV was
      found to be similar with all three doses and ranged from 325 to 401 min.
      Elimination rate constant (lambda z) and vitreal clearance of diesters increased
      with the ester chain length. Vitreal elimination half-lives of GCV diacetate,
      dipropionate, and dibutyrate esters were found to be 112 +/- 37, 41.9 +/- 13.1,
      and 33.5 +/- 6.5 min, respectively. Mean residence time (MRT) of regenerated GCV
      (356 +/- 16 min, 341 +/- 11 min and 324 +/- 19 min from GCV diacetate,
      dipropionate and dibutyrate, respectively) increased by 2-fold following prodrug
      administration as compared to direct GCV administration (185 +/- 28 min).
      CONCLUSIONS: GCV showed linear kinetics in the dose range studied. Acyl diester
      prodrugs of GCV generated therapeutic concentrations of GCV in vivo. Moreover,
      these studies have shown that MRT of GCV could be enhanced about 2-fold through
      prodrug modification.

PMID- 14972714
TI  - UV dose-dependent caspase activation in a corneal epithelial cell line.
AB  - PURPOSE: To characterize the UVB radiation-dependent patterns of caspase
      activation and cell death in SV 40 immortalized corneal epithelial cells.
      METHODS: Cell death in immortalized human corneal epithelial cells (T-HCEC) was
      induced by exposure to low (50 mJ/cm2) and high (450 mJ/cm2) doses of UVB. Cell
      death morphology was examined by fluorescence microscopy using the cell death
      marker propidium iodide (PI). Apoptosis of T-HCEC was analyzed by DNA
      fragmentation assays, and enzyme activity was measured for caspase 3 and 9 by
      fluorophotometry. Changes in mitochondrial inner membrane potential were measured
      by flow cytometry using the fluorescent marker, rhodamine 123. Redistribution of
      cytochrome c, the upstream trigger of caspase 9, was measured in the cytosol
      fraction of T-HCEC following irradiation. RESULTS: PI staining revealed a
      fragmented staining pattern of the nucleus consistent with apoptosis in detached
      cells irradiated with low-dose UVB, while cells receiving high dose UVB
      demonstrated round, well bordered staining of the nucleus. Flow cytometry
      revealed irreversible mitochondrial damage in the high dose group shown by
      decreased levels of rhodamine 123 fluorescence. Cells in the low-dose group had
      intact mitochondrial inner membrane potential, increased cytosolic cytochrome c,
      and showed a significantly higher rate of DNA fragmentation and caspase
      activation than the high dose group. CONCLUSION: Low dose UVB caused cytochrome c
      redistribution, caspase activation and apoptosis of corneal epithelial cells,
      which was not observed at high irradiation levels of UVB.

PMID- 14972715
TI  - Wettability of silicone-hydrogel contact lenses in the presence of tear-film
      components.
AB  - INTRODUCTION: Modern application of soft contact lenses demands safe and
      comfortable wear over extended time periods up to one month. Lenses that exhibit
      and sustain complete water wetting allow thick tear-film deposition, minimize
      film rupture, and permit smooth tear recovery upon lid closure. Water contact
      angles determined using an air bubble captive on a lens best gauge the in-vivo
      wetting state. To achieve highly water wetting lenses demands that contact-angle
      hysteresis be eliminated and that the advancing and receding angles both approach
      zero. Since lens wear exposes the anterior surface to tear proteins, lens
      wettability should be measured in the presence of tear-film components. METHODS:
      A captive-bubble technique is applied to measure the advancing and receding
      contact angles of two commercial silicone-hydrogel lenses: PureVision (PV) and
      Focus Night & Day (CF) and a standard HEMA (hydroxethyl-methacrylate) hydrogel
      lens: Acuvue (AV). In the captive-bubble method, an air bubble immersed in
      aqueous solution is brought into contact with the contact lens. The contact angle
      through water during bubble expansion yields the receding angle. Bubble
      contraction gives the water advancing angle. Contact-angle hysteresis is the
      difference between the advancing and receding angles. RESULTS: In isotonic
      solution, all three lenses display considerable contact-angle hysteresis with
      advancing angles of almost 90 degrees. When lysozyme and/or mucin were added to
      the aqueous solution, hysteresis was eliminated, and equivalent and high water
      wetting was achieved for the three lenses. Only the advancing angle in isotonic
      solution provided discriminating evidence for differences in surface chemistry.
      Covalent attachment of polyethyleneglygol (PEG) to the PV lens surface achieved
      complete water wetting independent of the presence of tear protein in the
      solution. CONCLUSIONS: The captive-bubble technique provides contact angles that
      are relevant to on-eye lens wear. Both advancing and receding contact angles are
      important to lens wettability performance. When lysozyme and/or mucin are present
      in the solution, PV, CF, and AV lenses display low advancing and receding contact
      angles indicative of equivalent wettability performance. This result is due to
      molecular adsorption of the proteins onto the lens external surface. Covalently
      attached PEG on the PV lens not only provides complete water wetting but also
      minimizes or even eliminates protein adsorption.

PMID- 14972716
TI  - Bicarbonate promotes dye coupling in the epithelium and endothelium of the rabbit
      cornea.
AB  - PURPOSE: Examine the mechanism of bicarbonate maintenance of cell-to-cell
      coupling in rabbit corneal epithelium and endothelium. METHODS:
      Carboxyfluorescein was microinjected into rabbit corneal epithelial and
      endothelial cells. Adjacent cells were observed for fluorescence. Bathing
      solutions were buffered with bicarbonate, HEPES, phosphate, or acetate-citrate.
      The influence of intracellular pH and transmembrane voltage (V m ) were examined.
      RESULTS: Bicarbonate was the only buffer to increase dye coupling. Substitution
      of bicarbonate structural analogs bisulfite and carbamate in a HEPES-buffered
      solution increased dye coupling in both cell types. Intracellular pH and V m
      alterations in corneal epithelial cells bathed in HEPES vs. bicarbonate buffered
      media had no significant effects on dye coupling. CONCLUSIONS: Bicarbonate
      increases intercellular communication in the corneal epithelium and endothelium.
      This effect appears to result from an interaction of the bicarbonate molecule (or
      one of its structural analogs) with either gap junction proteins or an
      intermediary. We also demonstrate the presence of Cx43 in the rabbit corneal
      endothelium.

PMID- 14972717
TI  - Subjective and objective assessments of the effect of orthokeratology--a cross
      sectional study.
AB  - PURPOSE: To determine which clinical tests are useful in orthokeratology
      aftercare examination, and to examine the objective and subjective
      characteristics of a group of orthokeratology lens wearers. METHODS: Thirty
      orthokeratology subjects (8-19 years) who had been wearing orthokeratology lenses
      for over 12 months were recruited. Autorefraction, corneal topography,
      retinoscopy, subjective refraction and biomicroscopy were performed. Only left
      eyes results were analysed. Subjective ratings of symptoms and problems
      experienced by subjects were obtained using a questionnaire. RESULTS:
      Autorefraction yielded higher residual sphere and residual cylinder by -0.54 D
      and -0.39 D respectively while retinoscopy yielded higher residual sphere and
      residual cylinder by -0.20 D and -0.03 D respectively. Corneal toricity measured
      by autokeratometry and corneal topography overpredicted the residual cylinder by 
      2.02 D and -2.08 D respectively. The mean +/- SD residual spherical equivalent
      refractive error was -0.11 +/- 0.57 D and the mean +/- SD unaided
      postorthokeratology visual acuity was 0.08 +/- 0.14 logMAR. The unaided visual
      acuity was significantly related to the residual cylinder. Pigmented arc was
      present in 16 corneas (53%). The most common problems/symptoms experienced by the
      subjects were lens binding (73%), ocular discharge in the morning (69%) and blur
      distance vision (47%). Over 80% of the subjects found lens handling troublesome
      in varying degree. All, except two subjects (who disliked the lens handling),
      wanted to continue the treatment. CONCLUSIONS: History taking, subjective
      refraction, biomicroscopy and corneal topography are important in a routine
      orthokeratology aftercare examination. Corneal pigmented arc, ocular discharge in
      the morning and lens binding were the most common sign, symptom and problem
      respectively observed/ reported. Most orthokeratology lens wearers with low to
      moderate myopia and low astigmatism enjoyed reasonably good unaided post
      orthokeratology vision in the daytime.

PMID- 14972718
TI  - Influence of peripheral iridectomy on intravitreous penetration of topical
      nipradilol.
AB  - PURPOSE: Penetration of drug from the anterior chamber to the vitreous is
      substantial in aphakic eyes, but negligible in normal phakic eyes. The purpose of
      this study is to investigate the effect of the presence of peripheral iridectomy
      (PI) which bypasses iris-lens diaphragm on the drug penetration from the anterior
      chamber to the vitreous. METHODS: Twelve Japanese White rabbits underwent PI in a
      randomly chosen eye and the same procedures except removal of the peripheral iris
      in the contralateral eye. Nine weeks after the procedure, topical instillation of
      20 microl of 1% nipradilol into the both eyes was repeated three times at five
      minute intervals, and two hours later the animals were sacrificed and the both
      eyes were enucleated. Concentrations of nipradilol in the aqueous and vitreous
      were determined using a high-performance liquid chromatography. RESULTS: The
      concentrations of nipradilol were significantly greater in the eyes with PI than
      those in the contralateral control eyes in the aqueous (5636 +/- 1688 vs 2835 +/-
      663 ng/g, mean +/- standard error, n = 12, p = 0.0028) and in the anterior
      vitreous (11.9 +/- 2.5 vs 5.6 +/- 1.0 ng/g, p = 0.0047), while not in the
      posterior vitreous or in the posterior retina-choroid. The ratios of the
      nipradilol concentrations in the anterior or posterior vitreous to that in the
      aqueous were not significantly different between the both eyes. CONCLUSIONS: The
      presence of PI had little effect on the penetration of topically instilled
      nipradilol from the anterior chamber to vitreous.

PMID- 14972719
TI  - Alterations in lens protein tyrosine phosphorylation and phosphatidylinositol 3
      kinase signaling during selenite cataract formation.
AB  - PURPOSE: Protein tyrosine phosphorylation is an important event in the cell
      signal transduction process. Phosphatidylinositol-3 kinase (PI-3K) is an
      intracellular signal mediator and plays a key role in many cellular functions. In
      this study we have examined the changes in lens protein tyrosine phosphorylation
      and its impact on phosphatidylinositol 3-kinase (PI-3K) signaling during selenite
      cataract development. METHODS: Cataract was induced in 10 days old rat pups by a
      single sub-cutaneous injection of sodium selenite (30 microM/Kg body weight) and
      lenses were collected at different stages of cataract development.
      Immunoprecipitation and Western immunoblotting were employed to determine protein
      tyrosine phosphorylation, PI-3K activity and protein in lens cell extracts.
      Tyrosine kinase activity in lens membrane preparations was assayed in the
      presence of a synthetic substrate peptide and [32P]ATP. RESULTS: Protein tyrosine
      phosphorylation in the lens was disrupted before the onset of cataract. A
      decrease in tyrosine phosphorylation of lens proteins was observed within 2-3
      days of selenite injection (pre-cataract stage). The effect was much more
      prominent with the progression of cataract. The decrease in protein tyrosine
      phosphorylation correlated with the decrease in tyrosine kinase activity
      associated with the lens membrane fraction. Stimulation of normal rat lenses in
      organ culture with insulin and IGF-1 caused an increase in the phosphorylation of
      proteins, whose tyrosine phosphorylation status appeared to be diminished during
      cataract development. Insulin and IGF-1 also stimulated rat lens PI-3K activity.
      While there was no change in total PI-3K activity during the onset of cataract,
      the activity of PI-3K associated with tyrosine phosphorylated proteins decreased
      markedly in pre-cataract lenses. Further, the ability of IGF-1 to stimulate PI-3K
      activity was significantly reduced in lens epithelial cells treated with
      selenium. CONCLUSIONS: These studies show that signaling events involving the
      protein tyrosine phosphorylation process and activation of PI-3K are altered
      during selenite cataract formation and implicate defects in signal transduction
      mechanisms as contributing factors in the development of cataract.

PMID- 14972720
TI  - The effect of prematurity on tear production.
AB  - PURPOSE: To evaluate the effect of the birth weight and the postconceptional age
      on the tear production of preterm and term newborn infants and to evaluate the
      changes in tear production during the first two months of life. SUBJECTS-
      METHODS: Both eyes of medically stable term and preterm infants were included in
      the study. Based on postconceptional age and birth weight, we divided preterm
      infants into three groups. Then, we measured the basal and reflex tear secretions
      of both eyes by Schirmer tests before and after instillation of topical
      anesthetic agent. We performed initial tear measurements on the second day of
      life (between first 24 hours to first 48 hours after birth): and at 2 weeks, 4
      weeks and 8 weeks after birth. RESULTS: We tested a total of 138 infants (63
      preterm and 75 term), 72 males and 66 females. Schirmer-1-test of preterm and
      terms on the 2nd day of life revealed a mean basal tear secretion (BTS) of 4.8 +/
      4.1 and 8.8 +/- 3.2 mm, respectively (p < 0.0001). The mean reflex tear
      secretion (RTS) within 48 hours of life was 6.1 +/- 3.9 mm and 10.3 +/- 4.4 mm in
      preterm and term infants, respectively (p < 0.0001). The mean values of both
      basal and reflex tear secretion were significantly lower in the preterm than the
      term infants during the first two months of the life. In preterm infants, both
      basal and reflex tear secretions were found to be highly correlated with
      postconceptional age (r: 0.79 and 0.74, respectively, both p values: 0.001);
      however, there was a weak correlation with birth weight (r: 0.16 and 0.19,
      respectively, both p values: 0.01). Statistically significant differences for
      both BTS and RTS existed among the three postconceptional age groups: there were
      no such difference among the three different birth weight groups. We found no
      gender or laterality dependent (side of the eyes) differences in the tear
      production (both p values >0.05). CONCLUSIONS: Preterm infants have significantly
      reduced tear secretion compared with term infants. Postconceptional age, rather
      than birth weight, seems to be more correlated with the tear secretion. Sex and
      laterality does not appear to have an effect on tear production in infants. Tear
      production of preterm infants is significantly reduced than that of term infants
      during the first two months of life. Term infants increased their tear production
      significantly in each examination during the neonatal period while the preterms
      increase tear production significantly only at mean postconceptional age of eight
      and a half (8.5) months.

PMID- 14972739
TI  - A compartmental model of an external urethral sphincter motoneuron of Onuf's
      nucleus.
AB  - This article discusses a model of the electrical behavior of an external urethral
      sphincter motoneuron, based on morphological parameters like soma size, dendritic
      diameters and spatial dendritic configuration, and several electrical parameters.
      Because experimental data about the exact ion conductance mix of external
      urethral sphincter neurons is scarce, the gaps in knowledge about external
      urethral sphincter motoneurons were filled in with known data of alpha
      motoneurons. The constructed compartmental model of motoneurons of Onuf's nucleus
      contains six voltage-dependent ionic conductances: a fast sodium and potassium
      conductance and an anomalous rectifier in the soma; a fast delayed rectifier type
      potassium conductance and a fast sodium conductance in the initial axon segment;
      an L-type calcium channel in the dendritic compartments. This paper considers the
      simulation of external urethral sphincter motoneuron responses to current
      injections that evoke bistable behavior. Simulations show self-sustained
      discharge following a depolarizing pulse through the microelectrode; the firing
      was subsequently terminated by a short hyperpolarizing pulse. This behavior is
      highly functional for neurons that have to exhibit prolonged activation during
      sphincter closure. In addition to these 'on' and 'off ' responses, we also
      observed a particular firing behavior in response to long-lasting triangular
      current pulses. When the depolarizing current was slowly increased and then
      decreased (triangular pulse) the firing frequency was higher during the
      descending phase than during the initial ascending phase.

PMID- 14972740
TI  - The effects of interval training on oxygen pulse and performance in supra
      threshold runs.
AB  - The aim of this study was to examine (i) the effects of a severe interval
      training period on oxygen pulse kinetics (O2-p, the ratio between VO2 and heart
      rate), and (ii) to study the consequences of these effects on the variation of
      performance (time to exhaustion) during severe runs. Seven athletes were tested
      before and after an eight-weeks period of a specific intermittent training at v
      Delta 50, i.e., the intermediate velocity between the lactate threshold (vLT) and
      the velocity associated with VO2max (vVO2max ). During the test sessions,
      athletes performed an incremental test and an all-out test at the pretraining v
      Delta 50. After the training period they also completed an additional all-out
      test at the posttraining v Delta 50 (v Delta 50bis). Results showed that after
      training there was i) an increase in the O2-p maximal value during the
      incremental test (22.7 +/- 1.5 mlO2.b-1 vs. 20.6 +/- 1.5 mlO2.b-1; p < 0.04), ii)
      a decrease in the time to reach the O2-p steady state (TRO2-p ) at the same
      absolute v Delta 50 (33 +/- 7 s vs. 60 +/- 27 s; p < 0.04) and iii) an increase
      in the O2-p steady state duration (TSSO2-p) at the same absolute v Delta 50 (552
      +/- 201 s vs. 407 +/- 106 s; p < 0.04). However, there was no relationship
      between the improvement of these two O 2 -p kinetics parameters (TRO2-p and TSS
      O2-p) and those of the performance. This study found that after an individualised
      interval-training program conducted at the same absolute velocity, the O2-p
      kinetics reached a steady state quicker and for a longer duration than before
      training. This is however not related with the improvement of performance.

PMID- 14972741
TI  - Effects of pre-exercise listening to slow and fast rhythm music on supramaximal
      cycle performance and selected metabolic variables.
AB  - We examined the effect of listening to two different types of music (with slow
      and fast rhythm), prior to supramaximal cycle exercise, on performance, heart
      rate, the concentration of lactate and ammonia in blood, and the concentration of
      catecholamines in plasma. Six male students participated in this study. After
      listening to slow rhythm or fast rhythm music for 20 min, the subjects performed
      supramaximal exercise for 45 s using a cycle ergometer. Listening to slow and
      fast rhythm music prior to supramaximal exercise did not significantly affect the
      mean power output. The plasma norepinephrine concentration immediately before the
      end of listening to slow rhythm music was significantly lower than before
      listening (p < 0.05). The plasma epinephrine concentration immediately before the
      end of listening to fast rhythm music was significantly higher than before
      listening (p < 0.05). The type of music had no effect on blood lactate and
      ammonia levels or on plasma catecholamine levels following exercise. In
      conclusion, listening to slow rhythm music decreases the plasma norepinephrine
      level, and listening to fast rhythm music increases the plasma epinephrine level.
      The type of music has no impact on power output during exercise.

PMID- 14972742
TI  - The effect of regular swimming exercise on vitamin E supplemented male rats.

PMID- 14972743
TI  - Effects of U-46619 on pulmonary hemodynamics before and after administration of
      BM-573, a novel thromboxane A2 inhibitor.
AB  - We studied the effects on pulmonary hemodynamics of U-46619, a thromboxane A2
      (TXA2) agonist, before and after administration of a novel TXA2 receptor
      antagonist and synthase inhibitor (BM-573). Six anesthetized pigs (Ago group)
      received 6 consecutive injections of U-46619 at 30-min interval and were compared
      with six anesthetized pigs (Anta group) which received an increasing dosage
      regimen of BM-573 10 min before each U-46619 injection. Consecutive changes in
      pulmonary hemodynamics, including characteristic resistance, vascular compliance,
      and peripheral vascular resistance, were continuously assessed during the
      experimental protocol using a four-element Windkessel model. At 2 mg/kg, BM-573
      completely blocked pulmonary hypertensive effects of U-46619 but pulmonary
      vascular compliance still decreased. This residual effect can probably be
      explained by a persistent increase in the tonus of the pulmonary vascular wall
      smooth muscles sufficient to decrease vascular compliance but not vessel lumen
      diameter. Such molecule could be a promising therapeutic approach in TXA2
      mediated pulmonary hypertension as it is the case in pulmonary embolism,
      hyperacute lung rejection and endotoxinic shock.

PMID- 14972744
TI  - Effects of BM-573, a novel thromboxane A2 inhibitor, on pulmonary hemodynamics in
      endotoxic shock.
AB  - Thromboxane A2 is considered to be partially responsible for the increase in
      pulmonary vascular resistance observed after endotoxin administration and to
      participate in proinflammatory reactions. The effects of a novel dual TXA2
      synthase inhibitor and TXA2 receptor antagonist (BM-573) on pulmonary
      hemodynamics were investigated in endotoxic shock. 30 mins before the start of a
      0.5 mg/kg endotoxin infusion, 6 pigs (Endo group) received a placebo infusion and
      6 other pigs (Anta group) received a BM-573 infusion. In Endo group, pulmonary
      artery pressure increased from 25 +/- 1.8 (T0) to 42 +/- 2.3 mmHg (T60) (p <
      0.05) after endotoxin infusion while, in Anta group, it increased from 23 +/- 1.6
      (T0) to 25 +/- 1.5 mmHg (T60). This difference is due to a reduction in pulmonary
      vascular resistance in Anta group while pulmonary arterial compliance changes in
      Endo group remained comparable with the evolution in Anta group. In Endo group,
      PaO2 decreased from 131 +/- 21 (T0) to 74 +/- 12 mmHg (T300) (p < 0.05), while in
      Anta group, PaO2 was 241 +/- 31 mmHg at the end of the experimental period
      (T300). These results demonstrate that TXA2 plays a major role in pulmonary
      vascular changes during endotoxin insult. Concomitant inhibition of TXA2
      synthesis and of TXA2 receptors by BM-573 inhibited the pulmonary vasopressive
      response during the early phase of endotoxin shock as well as the deterioration
      in arterial oxygenation.

PMID- 14972745
TI  - Dietary L-arginine restores aspirin-induced endothelial dysfunction in rat aorta.
AB  - L-Arginine induced elevation of the vascular prostanoid led us to think that the
      risk of coronary spasm may increase in L-arginine consumers when they are
      subjected to cyclooxygenase inhibitors and this limits the therapeutic value of
      aspirin. So the aim was to investigate the interaction of aspirin and dietary L
      arginine in male rats. Animals were divided into four groups and fed with normal
      food. The first group received tap water while the second, third and fourth
      groups were subjected daily to aspirin (8.6 mg/kg), L-arginine (143 mg/kg) and
      aspirin + L-arginine combination in their drinking water respectively for 7 days.
      Vasomotor responses were recorded in the aortic rings suspended for isometric
      force recordings. Aspirin treatment significantly reduced the dilation to
      acetylcholine and sodium nitroprusside. Attenuated phenylephrine contractility
      was associated with normal acetylcholine response in L-arginine group. Addition
      of L-arginine to aspirin treatment completely prevented aspirin-induced
      endothelial dysfunction but defective response to sodium nitroprusside persisted.
      Dietary L-arginine without affecting maximal dilation to acetylcholine
      significantly increased the share of dilator prostanoid which appears to resist
      aspirin. These results demonstrated that dietary L-arginine increases dilator
      prostaoid in rat aortic rings. Contrary to our expectation, co-administered L
      arginine protected aspirin induced endothelial dysfunction and ruled out the
      limitation of aspirin use in L-arginine consumers.

PMID- 14972746
TI  - Evidence that nitroprusside stimulates glucose uptake in isolated rat
      cardiomyocytes via mitogen-activated protein kinase.
AB  - Sodium nitroprusside (SNP), a nitric oxide (NO.) donor, stimulates glucose uptake
      in skeletal muscle. We investigated the stimulatory effect of SNP on glucose
      uptake in cardiomyocytes and the possible role of soluble guanylate cyclase,
      phosphatidylinositol-3-kinase (PI-3-kinase) and the mitogen-activated protein
      kinases (MAPKs). Cardiomyocytes were isolated from adult male Wistar rats by
      trypsin/collagenase perfusion and glucose uptake determined from the accumulation
      of 3H-2-deoxyglucose. SNP caused a dose-dependent increase in glucose uptake with
      200-300% increase at 30 mM. Cytochalasin B completely prevented the SNP-induced
      increase in glucose uptake. 8-Br-cGMP (100 microM) and the NO. donor
      spermineNONOate (100 microM) were without effect on basal glucose uptake. SNP
      stimulated glucose uptake was not inhibited by the guanylate cyclase inhibitor
      ODQ (10 microM). Sodium ferrocyanide (Na4Fe(CN)6), a compound structurally
      related to SNP, but without any NO. group, also stimulated glucose uptake in
      cardiomyocytes suggesting that the effect of SNP could be unrelated to liberation
      of NO. Wortmannin, an inhibitor of PI-3-kinase, inhibited insulin-stimulated
      glucose uptake completely but did not affect SNP-stimulated glucose uptake. SNP
      stimulated glucose uptake was inhibited by 50 microM PD 098059 (inhibitor of the
      MAPK-kinases that activate external regulated kinase [ERK1/2]) and by 50 microM
      SB203580 (inhibitor of p38MAPK). In conclusion, high SNP concentrations dose
      dependently stimulate glucose uptake in cardiomyocytes and our data suggest a
      role for MAPK signalling, but not PI-3-kinase and soluble guanylate cyclase, in
      stimulation of glucose uptake.

PMID- 14972747
TI  - Lithium action on adrenomedullary and adrenocortical functions and serum ionic
      balance in different age-groups of albino rats.
AB  - The aim of the current study was to investigate lithium action on adrenomedullary
      and adrenocortical functions and on serum ionic balance in rats. Three age-groups
      of male rats (juvenile: 30 days, adult: 100 days and aged: 3 years) were used.
      Each age-group of animal was exposed to short- (10 days) and long-term (25 days)
      treatments with lithium. Each age-group of rat received lithium at a dose 2mEq/kg
      body weight daily for 10 and 25 days. Each daily dose (2mEq) was divided equally
      into half (1 mEq) and each half was injected intraperitoneally twice (at 9 am and
      9 pm) for both the durations of experiments. Control animals received
      physiological saline for similar duration of experiments. Thirty animals were
      used for each age-group and they were divided equally into 6 groups with 5 each.
      After termination of all the experiments rats were sacrificed and, adrenal glands
      were quickly dissected out and processed for epinephrine, norepinephrine and
      corticosterone estimations and, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSDH)
      activity of the adrenal gland. Blood was drawn from the heart of each rat and,
      serum was collected and stored at -20 degrees C until assayed for lithium,
      calcium, sodium, potassium and corticosterone concentrations. The findings
      revealed that lithium in both short- and long-term treatments was maintained well
      within the therapeutic range (0.3-0.8 mEq/l) in all the age-groups of rats. This
      alkali metal caused depletions of both epinephrine and norepinephrine
      concentrations from adrenal glands, and elevations of corticosterone in both
      adrenal and blood serum of each age-group of rat (juvenile, adult and aged).
      Additionally adrenal 3beta-HSDH activity was also increased in all the age-groups
      of rats irrespective of duration of the treatments. Short-term treatment of
      lithium elevated only serum K+ level in juvenile and adult rats and, Ca+ level
      only in adult animals. Significant elevations of serum K+ and Ca+ levels were
      observed following long-term treatments of lithium in all the age group of rats.
      No significant change in serum Na+ level was recorded after lithium treatment,
      irrespective of duration of treatments, in any age-group of rats. The findings
      suggest that lithium action, in respect of adrenomedullary and adrenocortical
      functions and, serum ionic balance, may not be largely related to the age-group
      of rats and that, lithium acts on adrenomedullary activity probably by
      stimulating the release mechanism of epinephrine and norepinephrine from the
      adrenal gland of rats, but stimulates adrenocortical activity by stimulating both
      synthesis (including 3 beta-HSDH activity) and release of corticorterone.
      Simultaneously, lithium disturbs normal ionic balance by elevating K+ and Ca+
      levels in all the age-group of rats. Thus, the antimanic drug certainly disturbs
      both adrenomedullary and adrenocortical functions and, serum ionic balance in all
      the age-group of rats.

PMID- 14972748
TI  - LH response (in vivo and in vitro) to an LHRH agonist administered to domestic
      male cats.
AB  - We investigated plasma luteinizing hormone (LH) concentration in domestic male
      cats challenged with Luteinizing Hormone Releasing Hormone Analog (LHRH-A) [des
      Gly 10, (DTrp6)-LHRH ethylamide] that mediates the function of the hypothalamic
      pituitary-gonadal axis (HPG). Plasma LH concentrations in cats treated daily with
      LHRH (10 microg/100 microl/kg/day, subcutaneously-s.c.) for 19 days (LHRH group)
      and in controls treated with saline (NaCl-0.9%, same volume-SAL group) were
      chronically studied. LHRH administration (s.c.) for 15 days induced a significant
      fall (P < 0.05) in plasma LH concentrations during the chronic study. After the
      15th day of treatment the groups were divided once more into animals treated with
      LHRH (10 microg/100 microl/kg) or saline (i.v.), and a time course study (300
      min) was performed (acute study). Next, four groups of cats were compared in an
      acute study involving the s.c./i.v. administration of SAL/SAL, SAL/LHRH,
      LHRH/SAL, and LHRH/LHRH. The responses of the SAL animals challenged by acute
      i.v. administration of LHRH (group SAL/LHRH) were significantly higher (P < 0.01)
      than those of animals treated with LHRH (sc) (group LHRH/LHRH). LH release was
      also significantly increased in the latter group (P < 0.05), although the effect
      was short lasting, being recorded only at the first observation (45 min). An in
      vitro study with the pituitaries was also performed on day 20. Mean (+/-SEM) LH
      concentrations in the culture medium containing pituitaries with LHRH (10(-7) M)
      or saline were determined. In vitro analysis of these pituitaries demonstrated a
      significantly reduced response (P < 0.05) by animals treated sc with LHRH for 19
      days. This study represents a source of data for the domestic cat going beyond
      its own physiology. Serving as a model, this animal provide important information
      for the study of reproductive physiology in other members of its family
      (Felidae), almost all of them threatened with extinction.

PMID- 14972749
TI  - Renal mechanisms involved in stress-induced antinatriuresis and antidiuresis in
      rats.
AB  - The present study was conducted to investigate if changes in sodium and water
      excretion in stressed animals were due to modifications in the glomerular
      filtration rate (GFR) and to determine the participation of angiotensin II (Ang
      II) and alpha and beta-adrenoceptors on sodium and water renal excretion in rats
      subjected to immobilization stress (IMO). Male Wistar rats (250-300 g) were
      randomly separated into five different groups and vehicle (0.9% NaCl) via
      intraperitoneal (i.p.) or propanolol (3 mg/kg i.p.) or captopril (6 mg/kg i.p.)
      or yohimbine (3 mg/kg i.p.) or prazosin (1 mg/kg i.p.) were injected
      respectively. During experimental measurements, the animals were kept in
      metabolic cages for 6 h and sodium, potassium and water renal excretion and
      saline (1.5% NaCl) and water intake were determined at day 1 (drug effect) and
      day 7 (drug + IMO effects). GFR was measured by creatinine clearance in control
      and IMO rats. A stress-induced antinatriuresis and antidiuresis was reversed by
      alpha 1 and alpha 2-adrenoceptor antagonists, while captopril inhibited only the
      antidiuresis and propranolol had no effect on either parameter. No differences
      were observed in creatinine clearance in the studied groups. Since yohimbine
      blocks alpha 2-adrenoceptors and prazosin blocks alpha 1-adrenoceptors and alpha
      2B-adrenoceptors, the stress-induced renal sodium reabsorption mainly could be
      attributed to alpha 2B-adrenoceptors. The present results indicate that beta
      adrenoceptors do not participate in this response and, Ang II only reverses the
      antidiuresis and shows a slight participation in antinatriuresis. The increment
      in sodium and water reabsorption caused by IMO occurred without changes in the
      glomerular filtration rate.

PMID- 14972750
TI  - Use of a simple fractionation method to evaluate binding, internalization and
      intracellular distribution of oligonucleotides in vascular smooth muscle cells.
AB  - Antisense oligonucleotides (ODN) are potent molecules that could be used to
      inhibit the synthesis of a protein specifically if delivered to the appropriate
      compartments (cytoplasm and nucleus) of the cell under study. We present here a
      simple method providing access to the fractions of internalized ODN available in
      the cytosolic and nuclear compartments. Cells are incubated with appropriately
      labeled ODN, either naked or vectorized. They are then washed and treated with
      pronase to remove species bound to the surface of the cell. Digitonin is added at
      a low concentration to induce leakage of the cytosol, which is collected.
      Endosomes and lysosomes are then lysed with Triton X100, and their contents,
      recovered by centrifugation. The crude nuclei comprising the pellet are purified
      by ultracentrifugation through a 2M sucrose cushion. Lactate dehydrogenase,
      fluorescent transferrin and cathepsin B are used as cytosolic, endosomal and
      lysosomal markers respectively. For vascular smooth muscle cells, the use of
      digitonin under optimal conditions (0.008% w/v, 4 degrees C for 5 min) resulted
      in more than 88% plasma membrane permeabilization, with less than 12% of
      endosomes and 5% of lysosomes lysed. We mainly studied a 3'-tritiated 20-mer ODN
      sequence complementary to the AUG region of the mRNA for the insulin-like growth
      factor 1 receptor, with either a phosphodiester (PO-ODN) or a phosphorothioate
      (PS-ODN) backbone. Cellular processing was evaluated with and without 25 kDa
      polyethylenimine (PEI) as a carrier. After 2.5 h of incubation at 37 degrees C,
      100 times as much naked PS-ODN as naked PO-ODN was bound to the cell surface and
      internalized. Complexation with PEI dramatically increased both binding, by a
      factor of 10 and internalization by a factor of 80 of PO-ODN and, to a lesser
      extent, of PS-ODN. The intracellular distributions of naked PO-ODN and PS-ODN
      were similar. The radioactivity accumulated in nuclei accounted for about 15-20%
      of an intracellular radioactivity. A large proportion (about 60%) of
      intracellular radioactivity remained associated with the endocytic compartment.
      Complexation with PEI completely changed intracellular distributions: the nuclear
      fraction increased to 70% for PS-ODN. The fractionation method proposed,
      facilitating study of the subcellular distribution of the ODN, could also be used
      under appropriate circumstances, to study variations in cytosolic ODN content.

PMID- 14972751
TI  - Axonal misdirection as contributing factor to aberrant reinnervation of muscles
      after facial nerve suture in cats.
AB  - Abstract Whereas basic features of post-axotomy muscle reinnervation have been
      extensively studied in rats, little is known about axonal regrowth and
      pathfinding in cats. To address the question, adult cats were subjected to facial
      facial anastomosis (FFA). First group served to establish optimal parameters for
      labeling of the zygomatic and buccal facial branches with 1,1'dioctadecyl
      3,3,3,'3'-tetramethylindo-carbocyanine perchlorate (DiI) and Fast Blue (FB)
      placed onto respective transected nerves. The second group of animals underwent
      identical bilateral labeling 3 months after transection and suture of the right
      facial nerve. This group served to establish the number of motoneurons, which had
      branched after surgery and projected into both facial branches. On control side,
      DiI application onto zygomatico-orbital branch labeled 3883 +/- 598 (mean +/-
      S.D.) perikarya were confined to the dorsal and intermediate facial subnuclei,
      meanwhile an application of FB onto the buccal branch labeled 1617 +/- 552
      perikarya in the lateral and ventrolateral subnuclei. There were no double
      labeled cells. Three months after FFA all retrogradely labeled motoneurons were
      scattered throughout the entire facial nucleus. To establish the proportion of
      perikarya, that re-grew multiple axonal branches into both nerves, double-labeled
      (FB + DiI) motoneurons were counted from digital images. The zygomatico-orbital
      nerve contained 3311 +/- 430 DiI-labeled whereas the buccal nerve 1500 +/- 442 FB
      labeled motoneurons. The occurrence of 311 +/- 103 double-labeled perikarya
      (DiI+FB) suggested that approximately 6% of all retrogradely labeled motoneurons
      branched axons into both nerves. I conclude that malfunctioning axonal
      pathfinding rather than deviant reinnervation contributed to poor recovery of
      function after FFA in the cat.

PMID- 14972752
TI  - Creative innovation: possible brain mechanisms.
AB  - This article reviews and develops some theories about the neurobiological basis
      of creative innovation (CI). CI is defined as the ability to understand and
      express novel orderly relationships. A high level of general intelligence, domain
      specific knowledge and special skills are necessary components of creativity.
      Specialized knowledge is stored in specific portions of the temporal and parietal
      lobes. Some anatomic studies suggest that talented people might have alterations
      of specific regions of the posterior neocortical architecture, but further
      systematic studies are needed. Intelligence, knowledge and special skills,
      however, are not sufficient for CI. Developing alternative solutions or divergent
      thinking has been posited to be a critical element of CI, and clinical as well as
      functional imaging studies suggest that the frontal lobes are important for these
      activities. The frontal lobes have strong connections with the polymodal and
      supramodal regions of the temporal and parietal lobes where concepts and
      knowledge are stored. These connections might selectively inhibit and activate
      portions of posterior neocortex and thus be important for developing alternative
      solutions. Although extensive knowledge and divergent thinking together are
      critical for creativity they alone are insufficient for allowing a person to find
      the thread that unites. Finding this thread might require the binding of
      different forms of knowledge, stored in separate cortical modules that have not
      been previously associated. Thus, CI might require the co-activation and
      communication between regions of the brain that ordinarily are not strongly
      connected. The observations that CI often occurs during levels of low arousal and
      that many people with depression are creative suggests that alterations of
      neurotransmitters such as norepinephrine might be important in CI. High levels of
      norepinephrine, produced by high rates of locus coeruleus firing, restrict the
      breadth of concept representations and increase the signal to noise ratio, but
      low levels of norepinephrine shift the brain toward intrinsic neuronal activation
      with an increase in the size of distributed concept representations and co
      activation across modular networks. In addition to being important in divergent
      thinking, the frontal lobes are also the primary cortical region that controls
      the locus coeruleus-norepinephrine system. Thus creative people may be endowed
      with brains that are capable of storing extensive specialized knowledge in their
      temporoparietal cortex, be capable of frontal mediated divergent thinking and
      have a special ability to modulate the frontal lobe-locus coeruleus
      (norepinephrine) system, such that during creative innovation cerebral levels of
      norepinephrine diminish, leading to the discovery of novel orderly relationships.

PMID- 14972753
TI  - Dissociations of visual recognition in a developmental agnosic: evidence for
      separate developmental processes.
AB  - We report the results of tests investigating the recognition of faces, places,
      and objects in a developmental agnosic, because dissociations of visual
      recognition in developmental agnosics provide insight into the separable
      procedures performing recognition and the developmental origins of these
      procedures. TA is a software engineer in his early 40s with developmental
      prosopagnosia. He performs normally on tests of low-level vision, and he names
      objects at the basic level normally. In order to compare his recognition
      abilities for different classes, we have presented him with a famous landmarks
      test, a famous faces test, and old/new discriminations involving unfamiliar
      faces, houses, natural landscapes, cars, horses, guns, sunglasses, and tools. He
      was impaired on the face recognition tests, but performed normally on the place
      recognition tests. He also showed severe impairments with horses and cars,
      borderline impairments with guns and sunglasses, and normal performance with
      tools. These results indicate that the developmental processes that assemble the
      procedures used for face recognition and certain types of object recognition are
      separate from those processes that produce the procedures used for place
      recognition.

PMID- 14972754
TI  - An investigation of verbal short-term memory and phonological processing in four
      children with Williams syndrome.
AB  - Abstract Although phonological processing is generally considered to be a
      proficiency in Williams syndrome (WS), there are very few studies which have
      extensively explored phonological processing abilities in WS. In this study, we
      re-assessed phonological processing in WS by exploring verbal STM and
      phonological awareness abilities in 4 children with WS (CA: 10-12 years) and two
      control groups, one matched for chronological age (CA) and the other matched for
      verbal mental age (VA). Our results confirm and extend previous claims of
      preserved phonological STM in WS by showing specifically preserved STM
      performance for non-words, compared to both VA and CA control groups. However, we
      observed that this was the case only for non-words where support of phonological
      and lexico-semantic knowledge was minimized, with reduced phonological and lexico
      semantic effects on STM performance. Furthermore, a more direct assessment of
      phonological processing abilities through phonological awareness tasks showed
      impaired performance for the 4 WS children. Our data confirm that STM for non
      words represents a real strength in WS but they do not support previous
      assumptions of a more general preservation of phonological processing abilities
      in WS. Implications for impaired and preserved cognitive processes underlying
      verbal STM and phonological awareness abilities in WS are discussed.

PMID- 14972755
TI  - Cerebellar agenesis: clinical, neuropsychological and MR findings.
AB  - Cases of cerebellar agenesis are rare. The degree of motor impairment is a matter
      of discussion. It has been claimed that normal motor function can be observed.
      Detailed descriptions of neurological findings, however, are lacking.
      Neuropsychological testing in cerebellar agenesis is of additional interest based
      on recent findings of impaired non-motor functions in cerebellar disease. The
      case of an elderly woman with cerebellar agenesis is presented. 3D-MR imaging was
      used to confirm the diagnosis. Neurological and neuropsychological examination
      was performed including video documentation (see the authors' own website). To
      assess deficits of motor learning eyeblink conditioning was investigated.
      Neurological examination revealed mild to moderate signs of cerebellar
      dysarthria, upper and lower limb ataxia and ataxia of stance and gait. Motor
      learning was affected as shown by inability to acquire conditioned eyeblink
      responses. In addition, neuropsychological testing disclosed mild to moderate
      deficits in IQ, planning behavior, visuospatial abilities, memory and attention.
      Cerebellar ataxia, although clearly present, was less than one would expect in
      almost complete absence of the cerebellum. Neuropsychological deficits, on the
      other hand, appeared to be more marked than one would expect in cerebellar
      disease. No conclusion, however, could be drawn whether impaired cognitive
      development and neuropsychological test performance were directly related to lack
      of cerebellar function, or caused by impaired motor development and performance.

PMID- 14972756
TI  - Dissociation between personal and extrapersonal neglect in a crossed aphasia
      study.
AB  - Abstract Several reports document crossed aphasia following a right cerebral
      infarct. However, few of them provide a detailed investigation of associated
      neuropsychological disorders. A personal neglect disorder with no difficulty in
      orienting attention in the contralesional space has not been frequently reported
      independently of lesion side for the language deficit. In most cases, the deficit
      is described in the acute period. We report the case of a patient who showed
      severe crossed aphasia several months after cerebral damage. In addition to his
      language deficit, he suffered from finger agnosia, acalculia, and right/left
      confusion. Although he was able to orient attention in the contralesional space,
      he had a persistent personal neglect disorder with severe difficulty in attending
      to his own body. Results suggest that right hemisphere language dominance does
      not preclude ipsilateral specialisation for other functions. Furthermore, the
      dissociation between the two spatial functions provides further confirmation that
      they are subserved by two independent systems.

PMID- 14972757
TI  - A double dissociation between the meanings of action verbs and locative
      prepositions.
AB  - Abstract We describe two patients who manifested opposite patterns of performance
      on test batteries that evaluated production, comprehension, and semantic analysis
      of action verbs on the one hand (e.g. smile, wave, run ) and locative
      prepositions on the other (e.g. in, on, over ). JP failed all of the verb tests
      but passed all of the preposition tests, suggesting impaired knowledge of the
      meanings of action verbs but intact knowledge of the meanings of locative
      prepositions. In contrast, RR exhibited the reverse dissociation: he passed many
      of the verb tests but failed all of the preposition tests, suggesting mostly
      intact knowledge of the meanings of action verbs but impaired knowledge of the
      meanings of locative prepositions. This behavioral double dissociation reflects
      the fact that the two categories of words differ along several conceptual
      parameters. To a large extent, the patients exhibited a neuroanatomical double
      dissociation as well, since JP's lesion is predominantly in the left frontal
      operculum whereas RR's is predominantly in the left inferior parietal lobe and
      the posterior superior temporal region. This constitutes preliminary evidence
      that the meanings of action verbs and locative prepositions are represented by
      partially independent neural networks in the brain.

PMID- 14972758
TI  - Suppression of complex visual hallucinatory experiences by occipital transcranial
      magnetic stimulation: a case report.
AB  - Abstract We report a patient with visual hallucinations and illusions along with
      an associated visual field defect after bilateral ischemic damage to his
      occipital visual cortex. These hallucinations were long-standing and of both
      simple and complex (well-formed) type. Application of low frequency (1 Hz)
      repetitive Transcranial Magnetic Stimulation (rTMS) to the occipital cortex led
      to a complete cessation of visual hallucinatory symptoms. The use of TMS to probe
      the neurophysiology, and possibly alleviate, visual hallucinatory experiences is
      discussed.

PMID- 14972759
TI  - Pragmatism and bioethics: diagnosis or cure?

PMID- 14972760
TI  - Is pragmatism well-suited to bioethics?
AB  - This paper attempts to defend pragmatic approaches to bioethics against
      detractors, showing how particular critics have failed or succeeded. The paper
      divides bioethics from a pragmatic point of view into three groups. The first
      group is called "bioethical pragmatism" that will be represented by two book
      chapters from the anthology, Pragmatic Bioethics. The second group is called
      "clinical pragmatism" championed by Fins, Baccetta, and Miller. Finally, a third
      group, which has roots in the legal tradition, has been called "freestanding
      pragmatism" and is portrayed by Grey, Posner, and Wolf. Each group has been
      criticized in journal articles, and, in turn, this paper critiques some of the
      (mis)understandings put forth by Tollefsen, Jansen, and Arras about the
      capabilities and status of pragmatism in bioethical discussions. Finally, it
      concludes with cautionary notes about pragmatic bioethics in hopes that
      pragmatists will learn from their own insights about the human condition and the
      discipline of bioethics.

PMID- 14972761
TI  - Reductionism, eclecticism, and pragmatism in psychiatry: the dialectic of
      clinical explanation.
AB  - Explanatory models in psychiatry reflect what clinicians deem valuable in
      rendering people's behavior intelligible and thus help guide treatment choices
      for mental illnesses. This article outlines some key scientific and ethical
      principles of clinical explanation in twenty-first century psychiatry. Recent
      work in philosophy of science, clinical psychiatry, and psychiatric ethics are
      critically reviewed in order to elucidate conceptual underpinnings of
      contemporary explanatory models. Many explanatory models in psychiatry are
      reductionistic or eclectic. The former restrict options for diagnostic and
      therapeutic paradigm choice, while the latter lack a well-defined theoretical
      basis. These two methodological approaches stand in a dialectical relation to one
      another insofar as clinicians often move from one approach to its antithesis,
      ultimately seeking a synthesis of the two approaches that satisfies clinical
      needs. Pragmatic considerations can help to transcend the
      reductionism/eclecticism dialectic. In the absence of a completed science of
      mental disorders, psychiatrists must tolerate ambiguity and uncertainty as they
      strive to integrate diverse explanatory concepts in a rigorous and evidence-based
      fashion. A pragmatic explanatory model in clinical psychiatry must focus on
      favorable treatment outcomes for patients by respecting the pluralistic,
      participatory, and provisional nature of psychiatric explanation.

PMID- 14972762
TI  - Pragmatic principles--methodological pragmatism in the principle-based approach
      to bioethics.
AB  - In this paper it will be argued that Beauchamp and Childress' principle-based
      approach to bioethics has strongly pragmatic features. Drawing on the writings of
      William James, I first develop an understanding of methodological pragmatism as a
      method of justification. On the basis of Beauchamp's and Childress' most recent
      proposals concerning moral justification in the fifth edition of their Principles
      of Biomedical Ethics (2001), I then discuss different aspects that the principle
      based approach and methodological pragmatism have in common.

PMID- 14972763
TI  - Rorty's pragmatism and bioethics.
AB  - In spite of the routine acknowledgement of Richard Rorty's ubiquitous influence,
      those who have invoked his name en route to advancing their case for a pragmatist
      bioethics have not given us a very clear picture of exactly how Rorty's work
      might actually contribute to methodological discussion in this field. I try to
      provide such an account here. Given the impressive depth and scope of Rorty's
      work during the past two decades, I make no pretense of presenting either a
      comprehensive or novel interpretation of his project. My primary aim here is
      simply to sketch what I take to be the implications of Rorty's neopragmatism for
      our methodological debates within bioethics. I conclude that the yield of Rorty's
      pragmatism for current methodological debates in bioethics is primarily negative,
      knocking the props out from under any pretensions to foundations and universal
      principles of right and wrong. His "professorial pragmatism" and philosophical
      trash disposal efforts would clearly sweep away some approaches based upon
      appeals to nature or universal human dignity, and his deflationary nominalist
      view of principles would threaten the foundations of some influential principlist
      approaches to bioethics.

PMID- 14972764
TI  - What good is a pragmatic bioethic?
AB  - Do bioethicists need yet another theoretical approach with which to frame their
      disagreements? Many pragmatists contend that pragmatism, unlike its liberal and
      utilitarian counterparts, is uniquely commendable in (a) beginning from our lived
      experiences and (b) locating those experiences amid our social relations. In
      place of an "abstract principlism," pragmatism offers a practical "bedside
      bioethic"; in lieu of "autonomy run amuk," pragmatism proposes an ethic rooted in
      our communal resources. To date, however, efforts to develop such a bioethic have
      been stymied by pragmatists' own abstract theoretical commitments, commitments
      that prevent them, most directly, from beginning with the lived experiences and
      communal resources of those who hold theological commitments. This self-imposed
      methodological constraint, I argue, has needlessly thwarted pragmatism's most
      striking methodological promise: its potential to cultivate productive debates
      among secular and theologically-informed participants.

PMID- 14972765
TI  - On the possibility of a pragmatic discourse bioethics: Putnam, Habermas, and the
      normative logic of bioethical inquiry.
AB  - Pragmatic bioethics represents a novel approach to the discipline of bioethics,
      yet has met with criticisms which have beset the discipline of bioethics in the
      past. In particular, pragmatic bioethics has been criticized for its excessively
      fuzzy approach to fundamental questions of normativity, which are crucial to a
      field like bioethics. Normative questions need answers, and consensus is not
      always enough. The approach here is to apply elements of the discourse ethics of
      Habermas and Putnam to the sphere of bioethics, in order to develop a normative
      structure out of the framework of bioethical inquiry as it stands. The idea here
      is that the process of inquiry contains its own normative structure as it aims to
      discover norms. Such an approach, which fuses pragmatic bioethics with discourse
      ethics (which equally draws on pragmatism), may rightly be called a "Pragmatic
      Discourse Bioethics."

PMID- 14972766
TI  - Pragmatic bioethics and the big fat moral community.
AB  - By articulating a Peircean strain of bioethical inquiry, Elizabeth Cooke
      admirably attempts to avert the anti-realism, subjectivism and focus on consensus
      that afflict much so-called "pragmatic" bioethics. Yet, like many of her Deweyan
      colleagues, she falls prey to the egalitarian conviction that inquiry should be
      undertaken by huge numbers of like-minded individuals, proceeding in accordance
      with an authoritative canon of rules of discourse. In this essay, I argue that
      Cooke's egalitarianism is inconsistent with her apparent commitment to Peirce,
      and that an alternative, libertarian account of inquiry is better and truer to
      Peirce.

PMID- 14972769
TI  - Recombinant Sendai virus for efficient gene transfer to human airway epithelium.
AB  - Recombinant Sendai virus (rSeV) infects respiratory epithelial cells in animal
      models and cultures of undifferentiated human nasal cells. It was the aim of this
      study to investigate the capability of rSeV to express a transgene in human
      airway epithelium. Differentiated human airway epithelial cells were generated
      using air-liquid interface culture techniques. Application of rSeV coding for
      green fluorescence protein (GFP) onto the apical surface (using a multiplicity of
      infection of 3) resulted in expression of the transgene in more than 90% of the
      cells followed by decreasing numbers of positive cells during the observation
      time of 3 weeks. The infection of human respiratory epithelial cells is mediated
      by sialic acid residues at the apical surface. Despite the secretion of
      interleukin (IL)-8 and the replication of rSeV in the epithelial cells, the
      authors could not detect any cytopathic effect after the infection. In
      conclusion, rSeV infects differentiated human airway epithelial cells with high
      efficiency. Transgene expression is transient and accompanied by the secretion of
      an inflammatory cytokine.

PMID- 14972770
TI  - Heart angiotensin-converting enzyme activity increased after intraperitoneal
      bleomycin administration in rat.
AB  - Angiotensin-converting enzyme (ACE) generates angiotensin II and degrades
      bradykinin. This ectopeptidase acts as a marker in pathologic conditions, showing
      tissue and vascular damage. In order to evaluate serum and tissue ACE activity in
      bleomycin-associated lung damage, the authors studied morphological and enzymatic
      alterations as well as blood pressure in male Sprague-Dawley rats. Animals were
      treated intraperitoneally with bleomycin (5 mg/kg) 3 times for 1 week. This
      subacute and therapeutic dose produced morphologically evident pulmonary damage
      characterized by alveolar septum thickness and collagen deposition. Bleomycin
      also had significantly lowered lung and aorta N-acetyl-beta-D-glucosaminidase
      (NAG) activity, whereas heart and serum NAG activity increased significantly.
      Serum ACE activity was significantly lower in the treated animals, and heart ACE
      activity increased significantly. Lung ACE activity and blood pressure did not
      change during the study. The authors conclude that heart ACE activity increased
      faster than pulmonary ACE and serum ACE is a good indicator of damage even in
      subacute therapeutic bleomycin doses.

PMID- 14972771
TI  - Efficient depletion of alveolar macrophages using intratracheally inhaled
      aerosols of liposome-encapsulated clodronate.
AB  - Rat alveolar macrophages (AMs) were depleted via intratracheal inhalation (ITIH)
      of clodronate-containing liposomes. AM depletion following ITIH delivery of
      clodronate liposomes was 33.2 +/- 14.2 on day 1, 88.1 +/- 6.2 on day 3, and 91.4
      +/- 1.8 on day 4 relative to control rats given saline-containing liposomes.
      Almost all (approximately 99%) of the AMs remaining at the 3-day time point were
      peroxidase negative, suggesting that immature macrophages were not recruited from
      the circulation to replace those undergoing cell death on that day. Only 0.5% +/-
      0.5% of bronchoalveolar lavage (BAL) cells were neutrophils at this time
      (normalized to controls). Whole-body inhalation did not induce as much AM
      depletion at 3 days (37.6% +/- 10.1%) and required larger amounts of liposome
      encapsulated clodronate compared to ITIH. Intratracheal instillation (as opposed
      to inhalation) of clodronate liposomes produced a significant inflammatory
      response characterized by the influx of both polymorphonuclear neutrophils (PMNs)
      and macrophages. In subsequent pilot studies, the response to intratracheally
      instilled crystalline silica (75 microg) was found to be markedly reduced in rats
      depleted of AMs by the ITIH method. We conclude that ITIH of clodronate liposomes
      in rats is both efficient and useful for examining the role of AMs in pulmonary
      toxicology.

PMID- 14972772
TI  - Postnatal expression of cytochrome P450 1A1, 2A3, and 2B1 mRNA in neonatal rat
      lung: influence of maternal nicotine exposure.
AB  - A critical factor contributing to the etiology or modification of respiratory
      disease is the ability of the lung tissue to activate or inactivate chemicals. In
      this study, the authors investigated the effect of maternal nicotine exposure
      during gestation and lactation on the expression mRNA of cytochrome P450 (CYP)
      CYP1A1, CYP2A3, and CYP2B1. Fetal rats were exposed to nicotine via maternal
      administration of nicotine (1 mg/kg body weight/day, subcutaneously); after
      birth, neonatal rats were exposed to nicotine via the mother's milk. Lung tissue
      of 1-, 7-, 14-, 21-, and 49-day-old rat pups were used. From weaning on postnatal
      day 21 up to postnatal day 49, the offspring received no nicotine. Using RNA dot
      blot techniques, our results show that CYP mRNA expression in lung tissue
      increased with age after birth. Maternal nicotine exposure had no influence on
      CYP1A1 mRNA, but resulted in a marked increase in the expression of CYP2A3 mRNA
      and CYP2B1 mRNA. The higher levels of CYP2A3 mRNA and CYP2B1 mRNA were maintained
      after weaning.

PMID- 14972773
TI  - Acute effects of sildenafil in patients with primary pulmonary hypertension
      receiving epoprostenol.
AB  - Epoprostenol therapy has improved survival in primary pulmonary hypertension;
      however, only two thirds of patients are alive 3 years after starting treatment.
      Combined therapy with sildenafil, a phosphodiesterase 5 inhibitor, may provide
      additional benefit. The authors prospectively evaluated the acute hemodynamic and
      biochemical effects of sildenafil and inhaled nitric oxide, alone and in
      combination, in 8 patients with primary pulmonary hypertension receiving chronic
      epoprostenol. Average duration of epoprostenol therapy was 2.9 +/- 1.6 years
      (mean +/- SD) and mean dose was 25.7 +/- 10.8 ng/kg/min. A single 50 mg dose of
      sildenafil decreased mean pulmonary arterial pressure 10% (P<.05), increased
      cardiac output 8%, and decreased pulmonary vascular resistance 24% (P<.005).
      Although nitric oxide led to a similar decrease in mean pulmonary arterial
      pressure of 10% (P<.05), cardiac output was unchanged, resulting in a decrease in
      pulmonary vascular resistance of only 13%, which was not statistically different
      from baseline. These results suggest that sildenafil has greater acute
      hemodynamic effects than nitric oxide and that it can further reduce pulmonary
      vascular resistance in patients already demonstrating a benefit from chronic
      epoprostenol.

PMID- 14972774
TI  - A comparison of asbestos and urban particulate matter in the in vitro
      modification of human alveolar macrophage antigen-presenting cell function.
AB  - The mechanism for how inhaled particles cause or exacerbate human diseases is not
      known. It is clear, however, that some particles are more bioactive than others.
      One possible mechanism may involve a modification of antigen-presenting cell
      function. In this study, 2 forms of asbestos (crocidolite and Libby amphibole)
      and PM(2.5) (an urban particle) were cultured with human alveolar macrophages
      (HAMs) to determine whether antigen-presenting cell (APC) function was altered.
      HAMs were exposed to the bioactive particles, asbestos and PM(2.5), for 24 hours,
      then isolated free of extracellular particulates and nonviable cells. Isolated
      HAMs were then cultured with autologous lymphocytes in an 11-day APC assay using
      tetanous toxoid as the antigen and the resulting culture supernatants were
      assayed for lymphocyte-derived cytokines. Asbestos exposure, regardless of type,
      up-regulated a TH1 lymphocyte-derived cytokine, interferon gamma (IFNgamma), and
      the TH2 lymphocyte-derived cytokines interleukin-4 (IL-4) and interleukin-13 (IL
      13). PM(2.5) exposure up-regulated all 3 cytokines also. Although cytokine
      production levels were significantly higher for the treatment compared to control
      cultures as a group, there was extreme variability in the responses between
      subjects. In addition, there was no correlation between an individual's cells'
      response to asbestos verses PM, suggesting that more than one possible mechanism
      exists for a particle-induced APC effect and individual differential
      sensitivities to inhaled bioactive particles. This work supports the hypothesis
      that some inhaled particles can modify immune function by directly affecting APCs
      thus up-regulating the normal lymphocyte response to antigens in the lung.

PMID- 14972776
TI  - Pharmacological mechanisms of naltrexone and acamprosate in the prevention of
      relapse in alcohol dependence.
AB  - Naltrexone and acamprosate may ultimately prove to be useful additions to
      pharmacotherapy for alcoholism by reducing relapse. Naltrexone is a relatively
      selective competitive antagonist at mu-opioid receptors, and this activity may
      explain its anti-relapse action either because endogenous opioids are involved in
      the positively reinforcing effects of alcohol and/or because these same
      transmitters are involved in the conditioned anticipation of these effects. In
      contrast, the pharmacology of acamprosate is still poorly understood. This is not
      surprising because it is a small flexible molecule with similarities to several
      neuro-active amino acids and is used in high doses. All these factors suggest
      that it may have multiple actions. Currently, the best explanation for the
      effects of acamprosate seems to be that it inhibits the glutamatergic transmitter
      system involved in both the negative reinforcing effects of alcohol and the
      conditioned "pseudo-withdrawal" that may be important in cue-induced relapse.

PMID- 14972777
TI  - Alcohol use disorders: screening and diagnosis.
AB  - The purpose of this article is to provide an overview of empirically supported,
      primarily self-report methods of screening and diagnosis related to alcohol use
      disorders (AUDs). The discussion of screening instruments focuses on the primary
      care setting, and the diagnosis instruments discussion centers on the alcohol
      (and other drug) treatment setting. The literature shows that the AUDIT and the
      CAGE are the most widely validated methods of screening for AUDs in primary care
      and may be applied readily in that context. Similarly, a number of instruments
      designed to derive DSM-IV (and ICD-10) AUD diagnoses, as well as constructs
      related to how AUDs are defined, are available and can meet a variety of clinical
      needs. Future research priorities include further development of brief methods to
      identify hazardous drinkers or individuals who have an AUD, as well as refinement
      of diagnosis instruments to increase their application across treatment settings
      and subpopulations.

PMID- 14972778
TI  - Dual diagnosis: alcoholism and co-morbid psychiatric disorders.
AB  - Although alcohol use disorders are commonly associated with co-morbid drug use
      and psychiatric disorders, such co-morbidity is frequently underdiagnosed and
      inadequately treated. This paper reviews the epidemiological, diagnostic, and
      treatment literature on the co-morbidity of alcoholism, with a focus on the most
      common co-morbid disorders: drug abuse, mood disorders, anxiety disorders, and
      antisocial personality disorder. The paper goes on to describe a number of
      promising approaches to the treatment of these common co-morbid disorders in
      alcoholics. Despite the difficulties inherent in treating dual diagnosis
      patients, the clinician must recognize that it is possible to derive valid
      diagnoses and deliver efficacious treatment to such patients.

PMID- 14972779
TI  - The role of psychosocial treatments in pharmacotherapy for alcoholism.
AB  - Medication treatment for alcohol use disorders often includes a psychotherapy
      component. The most appropriate psychotherapy to use may depend upon
      characteristics of the patient, the medication, the setting, and the experiences
      of the provider. To date, little empirical research has investigated these issues
      with respect to outcomes in clinical trials that combine pharmacotherapy and
      psychotherapy. This paper reviews seven major types of psychotherapy for
      treatment of alcohol use disorders: brief interventions, motivational enhancement
      therapy, cognitive-behavioral therapy, cue exposure therapy, behavioral
      treatments, behavioral marital therapy, and twelve-step therapy. The theoretical
      basis for and empirical evidence supporting the efficacy of the therapies are
      reviewed, with an emphasis on studies that provided pharmacotherapy in
      conjunction with psychotherapy. Directions for future research in this area are
      also suggested.

PMID- 14972780
TI  - Current pharmacotherapies of alcoholism: a U.S. perspective.
AB  - Advances in the neurobiology of addiction and improved clinical trial methodology
      have accelerated the evaluation of medication for alcoholism. While psychosocial
      interventions have been useful to reduce consumption and support abstinence,
      considerable improvement in treatment is needed. Medication can play a crucial
      role in the reduction of craving and drinking and the maintenance of abstinence.
      This article reviews pharmacotherapy for alcoholism with an emphasis on the
      perspective of the United States. The opiate antagonist naltrexone, the glutamate
      modulator acamprosate, and serotonergic agents will be highlighted in this
      review. In general, both naltrexone and acamprosate have been found in a number
      of studies to be efficacious agents for the treatment of alcohol dependence.
      Serotonin reuptake inhibitors have not consistently shown to be efficacious but
      may be useful in certain subgroups of alcoholics. The serotonin type-3
      antagonist, ondansetron, has shown promise in early-onset alcoholics but needs
      more extensive study.

PMID- 14972781
TI  - Use of acamprosate and opioid antagonists in the treatment of alcohol dependence:
      a European perspective.
AB  - In thirteen of sixteen placebo-controlled trials in Europe, acamprosate increased
      abstinence in detoxified alcohol-dependent patients. It is approved in most EU
      countries. Its action at N-methyl-D-aspartate (NMDA) receptors appears to account
      for many of its effects. The number needed to treat in the fifteen trials
      suitable for meta-analysis has been calculated at 8.15. Trials of naltrexone in
      Europe have shown less clear evidence of efficacy than trials of acamprosate,
      whether abstinence or relapse to heavy drinking is used as the outcome criterion.
      With reduction in heavy drinking days as the criterion, naltrexone compared
      favorably to acamprosate in an open study in moderate alcohol dependence; one
      double-blind study has pointed to an advantage of the combination of naltrexone
      with acamprosate over either drug. To date, there are no trials published of
      nalmefene in European clinics. While many centers routinely offer a trial of
      acamprosate to newly detoxified patients aiming for abstinence, naltrexone usage
      varies. Some centers suggest naltrexone not only for patients aiming for
      abstinence but also for patients for whom continued drinking is a therapeutic
      possibility or a clinical inevitability.

PMID- 14972782
TI  - A review of the molecular diagnosis of thalassemia.
AB  - The thalassaemias are a major health problem, and approximately 1 in 14 of the
      population are carriers for one of the sub types. For the purpose of prevention
      and control of clinically severe disease, molecular diagnosis either pre-natally
      or ante natal with genetic counselling are increasingly important. The majority
      of mutations causing the thalassaemias have now been characterised and a small
      number of common mutations cause the bulk of disease in each particular
      population-base. With little more than 6 to 8 common mutations probes over 90% of
      thalassaemic patients can now be characterised but challenges remain in the 10%
      where the mutations are rare, or have not yet been determined. Newer developments
      in micro array technology in combination with current PCR based systems will lead
      to further characterisation of this group and aid proper genetic potential
      identification and control of the disorder.

PMID- 14972783
TI  - A new aspect of the molecular pathogenesis of paroxysmal nocturnal
      hemoglobinuria.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematologic
      disorder which is manifest by complement-mediated hemolysis, venous thrombosis,
      and bone marrow failure. Complement-mediated hemolysis in PNH is explained by the
      deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins, CD55 and CD59
      on erythrocyte surfaces. All the PNH patients had phosphatidylinositol glycan
      class A (PIG-A) gene abnormalities in various cell types, indicating that PIG-A
      gene mutations cause the defects in GPI-anchored proteins that are essential for
      the pathogenesis of PNH. In addition, a PIG-A gene abnormality results in a PNH
      clone. Bone marrow failure causes cytopenias associated with a proliferative
      decrease of its hematopoietic stem cells and appears to be related to a pre
      leukemic state. Although it is unclear how a PNH clone expands in bone marrow, it
      is considered that the most important hypothesis implicates negative selection of
      a PNH clone, but it does not explain the changes in the clinical features at the
      terminal stage of PNH. Recently, it has been suggested that an immune mechanism,
      in an HLA-restricted manner, plays an important role in the occurrence or
      selection of a PNH clone and GPI may be a target for cytotoxic-T lymphocytes.
      Also, it has been indicated that the Wilms' tumor gene (WT1) product is related
      to a PNH clone, but the significance of WT1 expression is not clear because of
      the functional diversity of the gene. To elucidate this problem, it is important
      to know the pathophysiology of bone marrow failure in detail and how bone marrow
      failure affects hematopoietic stem cells and immune mechanisms in bone marrow
      failure syndromes.

PMID- 14972784
TI  - Incidence of aplastic anemia in a defined subpopulation from Mexico City.
AB  - Aplastic anemia (AA) is a hematological disease characterized by the deficient
      production of blood cells. The incidence of AA worldwide is low (1-5 new cases
      per 10(6) individuals per year). In contrast to other countries, no current
      reports exist on the incidence of this disorder in Mexico. In the present study,
      we have determined the incidence of AA in a defined subpopulation from Mexico
      City during the period 1996-2000. For the purpose of this study, we focused on
      the experience from a single medical institution: the Mexican Institute of Social
      Security (IMSS), which covers around 50% of Mexico's population. The incidence of
      AA was determined based on the actual number of patients diagnosed with this
      disease at the IMSS in Mexico City in a given year and the total number of
      individuals registered at the IMSS in Mexico City in the same year. Considering
      the IMSS population as a whole, the annual incidence of AA was 3.9 new cases per
      10(6) individuals per year. In the pediatric population, the annual incidence was
      4.2 new cases per 10(6) individuals per year, whereas in people 15-years-old and
      older the incidence was 3.8 new cases per 10(6) individuals per year. These
      incidences were higher than those reported in most studies from the USA, Europe
      and Israel. Compared to the incidence in Thailand, the incidence we observed in
      children was considerably higher, whereas the one in adults was similar to the
      one in that country. The results of the present study suggest that the incidence
      of AA in Mexico City is one of the highest worldwide, particularly in terms of
      the pediatric population; however, these results must be taken with caution since
      this study comprises only a subpopulation from Mexico City and not the entire
      population. Thus, further studies including a broader population, both in Mexico
      City and other urban and rural areas of this country, will be necessary in order
      to obtain better and more complete estimates of the actual incidence of AA in
      Mexico.

PMID- 14972785
TI  - Pregnancy associated aplastic anemia--a series of 10 cases with review of
      literature.
AB  - INTRODUCTION: Pregnancy induced aplastic anemia is a rare entity and the
      association is not well explained. There are approximately 80 cases in the
      literature and we are presenting the largest series, so far, of 10 cases.
      RESULTS: Total of 10 cases had 11 pregnancies. Mean age at presentation was 25.45
      years and mean gestation when symptoms first developed was 17.09 weeks. Pallor
      and bleeding manifestations were the most common presenting complaints. Mean Hb,
      TLC, ANC and platelets were 4.97 g/dl, 2.74 x 10(9)/l, 1.11 x 10(9)/l and 41 x
      10(9)/l, respectively. Bone biopsy cellularity ranged from <5 to 25%. Nine out of
      11 (81%) pregnancies were successful of which 7 was full term and 2 were
      premature. Two babies were small for dates. One spontaneous abortion and one
      intra uterine death (IUD) were observed. Two out of 11 mothers died due to
      disease after delivery. Two of the 8 surviving mothers, had spontaneous partial
      response (22%); 4 mothers were asymptomatic after therapy with immunosuppressives
      given for 6 months and 3 were lost to follow up without response. Specific
      therapy (cyclosporin) was tried in two mothers antenatally with partial response
      in one. One child whose mother was given cyclosporin antenatally had jejunal
      atresia at birth. CONCLUSION: Pregnancy associated aplastic anemia is a rare
      association. Spontaneous remission can occur in 25-30% of patients. In the first
      trimester patients, pregnancy can be terminated while in advanced pregnancy
      patients can be followed up with stringent supportive care. Cyclosporin may be a
      safe drug antenatally in such patients. Patients with established aplastic anemia
      should avoid pregnancy.

PMID- 14972786
TI  - Molecular heterogeneity of diffuse large B-cell lymphoma: implications for
      disease management and prognosis.
AB  - Diffuse large B-cell lymphoma (DLBCL) accounts for approximately 40% of all B
      cell non-Hodgkin lymphomas of the Western world. According to the "WHO
      classification of tumours of the haematopoietic and lymphoid tissues", the term
      DLBCL is likely to include more than one disease entity, as suggested by the
      marked variability of the clinical presentation and response to treatment of this
      disease. Such heterogeneity may reflect the occurrence of distinct molecular
      subtypes of DLBCL as well as differences in the host's immune function. In
      immunocompetent hosts, approximately 50% DLBCL carry one of two primary molecular
      lesions defining two distinct genotypic subgroups, characterized by activation of
      either the BCL-6 or the BCL-2 proto-oncogene. Conversely, the remaining DLBCL of
      immunocompetent hosts display one of several molecular lesions, each associated
      with a small subset of cases and including activation of the proto-oncogenes REL,
      MUC-1, BCL-8 and c-MYC. The molecular pathogenesis of immunodeficiency-associated
      DLBCL differs substantially from that of DLBCL in immunocompetent hosts. In fact,
      EBV infection is present in a large fraction of immunodeficiency-associated
      DLBCL, whereas it is consistently negative in DLBCL of immunocompetent hosts,
      probably reflecting the critical role of disruption of the immune system in this
      disease. Finally, the application of DNA microarray technology to DLBCL has led
      to the distinction of two disease variants: a germinal center like DLBCL and an
      activated peripheral B-cell like DLBCL. Overall the molecular features of DLBCL
      may identify prognostic categories of the disease and may represent a powerful
      tool for therapeutic stratification.

PMID- 14972787
TI  - Solitary plasmacytoma in the setting of Langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is an intriguing disorder characterized by
      the accumulation of specialized dendritic cells called Langerhans cells in
      several diverse tissues and body sites. It has been cited in numerous case
      reports to be associated with a wide variety of malignant neoplasms. Although
      many hypotheses have been suggested, the basis for such associations remains
      essentially unknown. We describe another association here that to our knowledge
      has not been reported thus far: a solitary plasmacytoma occurring at a site of
      previous involvement by LCH. This constitutes a new addition to the now fairly
      lengthy list of malignant neoplasms that have been reported to occur in the
      setting of LCH. The possible reasons for such an association are discussed along
      with a brief review of LCH.

PMID- 14972788
TI  - Successful treatment of aplastic variant of hairy-cell leukaemia with
      deoxycoformycin.
AB  - The case of a patient with the aplastic variant of hairy cell leukaemia,
      successfully treated with the drug Deoxycoformycin(Pentostatin), is presented. It
      is very important to be aware of this rare variant of a rare disease so that the
      right treatment can be offered.

PMID- 14972790
TI  - A comparative study on the effect of phenobarbitol and beta-methylcholanthrene on
      glutathione S-transferases of rat testis.
AB  - Glutathione S-transferases (GSTs; EC, 2.5.1.18) ubiquitously distributed in all
      life forms, are a family of multigene and multifunctional dimeric proteins, which
      play a main role in drug detoxication. On purification and on electrophoresis,
      rat testicular glutathione S-transferases showed that it comprises of four
      subunits, Yc of alpha class, Yb and Ybeta of mu class and Ydelta of pi class. On
      chromatofocusing they were resolved into six anionic and four cationic isozymes.
      The substrate specificity studies and immunoblot analysis of testis proteins
      revealed that Ydelta of pi class GST was induced predominantly in response to
      phenobarbitol and Yc of alpha class and Ybeta of mu class were elevated
      specifically on treatment with methylcholanthrene (MC). These results show that
      structural variation between the two carcinogens induces different types of GST
      subunits. Therefore, these subunits may be used as marker proteins for specific
      chemical toxicity of rat testis.

PMID- 14972791
TI  - Metformin attenuates blood lipid peroxidation and potentiates antioxidant defense
      in high fructose-fed rats.
AB  - The implication of oxidative stress in the pathology of insulin resistance has
      been shown recently. We investigated the effect of an insulin sensitizer,
      metformin, on the plasma lipid peroxidation and antioxidant defense system in the
      erythrocytes of high fructose fed rats which form an animal model of insulin
      resistance. The experimental animals were divided into two batches of 12 animals
      each. The control batch received the control diet, containing starch; the
      fructose group was given the high fructose diet. At the end of second week these
      were subdivided into two groups; one was given metformin (50 mg/kg/day in water)
      by gastric intubation and other group was left untreated. The rats were continued
      on the same dietary regimen for the next two weeks. Fructose-fed rats showed
      hyperglycemia, hyperinsulinemia and hypertriglyceridemia at the end of four
      weeks. Enhanced plasma lipid peroxidation and inadequate cellular antioxidant
      defense system were observed in them. Administration of metformin was associated
      with significant normalization of circulating insulin, glucose and triglyceride
      concentrations. The abnormal triglyceride distribution in the lipoprotein
      fractions was also ameliorated by metformin therapy. The imbalance between
      peroxidation and antioxidant defense system was mitigated when fructose-fed rats
      were treated with metformin. In the control rats, metformin did not affect the
      parameters studied. Significant positive correlation was obtained between
      insulin, triglycerides and glucose concentrations with lipid hydroperoxides
      suggesting that these metabolic variables could influence the lipid peroxide
      levels in plasma.

PMID- 14972792
TI  - Oxidative stress and tumor markers in cervical cancer patients.
AB  - Cervical carcinoma is the second most common cancer worldwide. The extent of free
      radical induced oxidative stress can be exacerbated by the decreased efficiency
      of antioxidant defense mechanisms. Low levels of essential antioxidants in the
      circulation have been found to be associated with an increased risk of cancer.
      The aim of our study was to assess the extent of oxidative stress, the levels of
      antioxidants like superoxide dismutase (SOD), catalase (CAT), ceruloplasmin and
      to evaluate tumor markers such as aspartate transaminase (AST), alanine
      transaminase (ALT), alkaline phosphatase (ALP) and total sialic acid (TSA) levels
      in circulation of women with cervical carcinoma and to compare our findings with
      age matched controls. Low levels of SOD and CAT observed in the circulation of
      cervical cancer patients may be due to their increased utilization to scavenge
      lipid peroxides as well as sequestration by tumor cells. Higher levels of TSA,
      AST, ALT and ALP, in the circulation of cervical cancer patients may be used in
      the diagnosis and treatment monitoring of patients with cervical carcinoma.

PMID- 14972793
TI  - Lead exposure and heat shock inhibit cell proliferation in human HeLa and K562
      cells by inducing expression and activity of the heme-regulated eIF-2alpha
      kinase.
AB  - We have used human cell lines, namely, K562 and HeLa cells as model systems in
      understanding the mechanism of lead toxicity and heat shock, that may be mediated
      by the heme-regulated eIF-2alpha kinase which is also called the heme-regulated
      inhibitor (HRI). RT-PCR analysis using HRI-specific primers indicated a two- to
      three-fold increase in HRI expression in K562 and HeLa cells exposed to lead
      acetate and heat shock, respectively. Further, in vitro eIF-2alpha kinase assay
      indicated a two- to three-fold increase in HRI kinase activity during lead
      toxicity in K562 cells. This increase in HRI expression and its activity was
      accompanied by a significant decrease in cell proliferation and cell viability.
      This is therefore, the first report indicating that both heavy metal exposure and
      heat shock cause inhibition of protein synthesis not by activation of HRI alone
      but by its over-expression as well as activation. Our data indicate further that
      lead-induced inhibition of cell proliferation may be caused due to inhibition of
      protein synthesis resulted due to induced expression and activity of HRI.

PMID- 14972794
TI  - Alpha-mannosidase from the seeds of Triticale.
AB  - Seeds of Triticale (hybrid of wheat and rye) contain an N-acetylglucosamine
      specific lectin that was affinity purified in our laboratory (Siva Kumar, N. and
      Padma, K. (1996) "Affinity purification of N-acetyl glucosamine specific lectin.
      Purification and partial characterization of Triticale lectin". Biochem. Mol.
      Biol. Int. 38, 1059-1066). Seed extracts also exhibited alpha-mannosidase
      activity that was isolated by a combination of ion exchange, hydrophobic
      chromatography and gel filtration. The purified enzyme is a glycoprotein with 7%
      carbohydrate and exhibited a native molecular mass of 1,95,000 (+/-5000) on
      Biogel P-200 and dissociated into two major subunits under reducing conditions of
      molecular masses 58 and 40 kDa, respectively. Both subunits cross-reacted with an
      antibody to the well-characterized jack bean alpha-mannosidase, suggesting
      antigenic similarity between the legume and the cereal mannosidases. Purified
      enzyme binds to Con A-Sepharose gel, possibly through the sugar-binding site.
      Purified Triticale enzyme was stable at 50 degrees C up to 20 min and did not
      show requirement of metal ions for activity. Phenylalanine was detected as the
      sole N-terminal amino acid in the purified enzyme.

PMID- 14972795
TI  - Determination of amino acid pairs sensitive to variants in human low-density
      lipoprotein receptor precursor by means of a random approach.
AB  - In this data-based theoretical analysis, we use the random approach to analyse
      the amino acid pairs in human low-density lipoprotein receptor (LDL receptor)
      precursor in order to determine which amino acid pairs are more sensitive to 127
      variants from missense mutant human LDL receptor. The rationale of this study is
      based on our hypothesis and findings that the harmful variants are more likely to
      occur at randomly unpredictable amino acid pairs, the unharmful variants are more
      likely to occur at randomly predictable amino acid pairs. This is because we
      argue that the randomly predictable amino acid pairs should not be deliberately
      evolved, whereas the randomly unpredictable amino acid pairs should be
      deliberately evolved with connection of protein function. The results show, for
      examples, 96.06% of 127 variants occur at randomly unpredictable amino acid
      pairs, which account for 80.44% of amino acid pairs in LDL receptor, and the
      chance of occurring of variant is about five times higher in randomly
      unpredictable amino acid pairs than in predictable pairs. Thus, the randomly
      unpredictable amino acid pairs are more sensitive to variants in human LDL
      receptor. The results also suggest that the human LDL receptor has the natural
      tendency to variants.

PMID- 14972796
TI  - Analysis of distributions of amino acids in the primary structure of apoptosis
      regulator Bcl-2 family according to the random mechanism.
AB  - It is no long a question whether the process of evolution is affected by chance,
      but is to what extent. The random analysis can throw light on the underlying
      reasoning for the primary structure of proteins. The study on the Bcl-2 family
      shows that the rank per amino acid increases 93% in bovine than in chicken and
      rat, which indicates that the effect of chance has more impact on the
      evolutionary process of chicken and rat Bcl-2 and less impact on bovine Bcl-2.
      About one fourth of types of amino acids distribute in the highest probabilistic
      way in the Bcl-2 family. These phenomena are striking in four BH regions where
      vast majority of amino acids occur with the probabilistically simplest
      distribution. Mutations and variants can lead to the increased and/or decreased
      distribution probabilities of amino acids. Mutations 1, 2 and variant 3 target
      the rank increased in both affected amino acids. By contrast variants 1 and 2
      lead to the rank decreased in both affected amino acids. In mutations 3 and 4,
      the affected amino acids change their ranks to opposite directions, i.e. the rank
      is lower in replaced amino acid and higher in replacing one. Using our random
      approaches as quantitative tools, we can measure, compare and explain the primary
      structures of proteins.

PMID- 14972797
TI  - Molecular cloning and sequence analysis of a cDNA encoding ornithine
      decarboxylase cDNA from chilli (Capsicum annuum).
AB  - Ornithine decarboxylase (ODC) is an enzyme of one of the two pathways of
      putrescine biosynthesis in plants. The genes encoding ODC have previously been
      cloned from Datura stramonium and human. Using differential screening, we
      isolated ODC cDNA clone from a cDNA library of ripening Capsicum annuum fruit.
      The cDNA clone designated CUKM10 contains an insert of 1523 bp. The longest open
      reading frame potentially encodes a peptide of 345 amino acids with an estimated
      molecular mass of 47 kDa and exhibit striking similarity to other ODCs.
      Expression analysis showed that the capODC hybridised to a single transcript with
      a size of 1.7 kb. The capODC transcript was first observed in early ripening and
      increased steadily until it reached fully ripening stage. From the observation it
      is suggested that capODC is developmentally regulated especially during later
      stage of ripening.

PMID- 14972798
TI  - Biochemical and physicochemical changes in collagen isolated from the gall
      bladder of gall stone patients.
AB  - Abnormal gall bladder motor function with delayed emptying and stasis are the
      contributory factors of gall stone formation. Since collagen is the major
      contractile protein, this study was designed to find out whether the biochemical
      and physicochemical changes of collagen contribute to the pathogenesis of gall
      stone formation. Collagen was isolated from the gall bladder of 25 gall stone
      patients undergoing cholecystectomy and from that of 20 gall stone free subjects.
      The levels of total, soluble and insoluble collagen were determined. The activity
      levels of collagenase (3.4.23.3) and protease (3.4.24.11) were assessed. Levels
      of susceptibility of collagen to denaturing agents 2 M potassium thiocyanate and
      8 M urea were estimated. Aldehyde content, shrinkage temperature and tensile
      strength were also determined in isolated collagen. SDS-PAGE was carried out and
      alpha, beta fractions were quantified. The total and insoluble collagen contents
      were significantly high in gall stone patients. The activity levels of
      collagenase and protease were significantly low. Elevated levels of lipid
      peroxides, aldehyde content, shrinkage temperature and tensile strength were
      observed in gall stone patients. There is a significant elevation in the beta
      fraction and a decrease in alpha/beta ratio. Ultramicroscopic structure of gall
      bladder revealed derangement of collagen fibres and altered tissue architecture.
      The results showed that the qualitative and quantitative alterations in collagen
      also contribute for the defective contractility and stasis of gall bladder in
      gall stone patients.

PMID- 14972799
TI  - Evidence for oxidative stress in the gall bladder mucosa of gall stone patients.
AB  - BACKGROUND: There is considerable evidence indicating that gall stone patients
      have altered gall bladder functions with respect to secretion and absorption and
      inflammation in mucus membrane when compared with gall stone free subjects.
      Increased levels of accelerated generation of reactive oxygen species and toxic
      degradative products of lipid peroxidation have been reported in the plasma of
      individuals with gall stones. The purpose of this study is to find out whether
      oxidative stress in mucosa plays any role in the pathogenesis of gall stone
      diseases. Levels of lipid peroxides, lipid hydroperoxides (LPH) and conjugated
      dienes were assessed in gall bladder mucosal scrapings obtained from 30 gall
      stone patients undergone cholecystectomy. Antioxidant enzymes such as catalase
      (EC 1.11.1.6), superoxidedismutase (EC 1.15.1.1), glutathione peroxidase (EC
      1.11.1.9), glutathione transferase (EC 2.5.1.18) and glutathione reductase (EC
      1.6.4.2) were assessed. The activity levels of alkaline phosphatase (EC 3.1.3.1),
      adenosine triphosphatase and protease (EC 3.4.24.11) were also assessed and data
      compared with identical data collected from 15 gall stone free subjects and 10
      post-mortem cases. Gall stone patients had significantly higher levels of
      conjugated dienes, LPH and thiobarbituric acid reacting substances in their gall
      bladder mucosa. Lower levels of glutathione and glutathione related enzymes,
      catalase and superoxide dismutase were observed in those patients when compared
      to gall stone free subjects. The activities of functional enzymes in mucosa such
      as alkaline phosphatase, Na(+)-K+ (EC 3.6.1.3) and Ca2+ (EC 3.6.1.2) adenosine
      triphosphatase showed significant decreases. Histopathological observation showed
      lipid accumulation, dilated blood vessels, necrotic and fibrotic changes and
      inflammation in the gall bladder mucosa of gall stone patients. The data show
      that gall stone patients have a high level of oxidative stress in the gall
      bladder mucosa, a finding that may be related to a decreased activity of
      functional enzymes in mucosal cells. Such a condition might result in an altered
      gall bladder absorption and secretion of bile components such as mucins and
      glycoproteins. The resultant increased risk of bile saturation would further
      contribute to the progress of gall stone formation.

PMID- 14972800
TI  - 2-Methylaminopyridine-copper (II) complex catalyzes protein degradation.
AB  - To investigate the mechanism of scission of proteins by the chemical cleaving
      agents like metal complexes, bovine serum albumin (BSA) has been treated by the
      copper(II) complex CuL2SO4, where L is 2-methylaminopyridine. BSA degradation
      increased with increasing the concentration of the copper complex. Copper complex
      rapidly degraded BSA at mild acidic and neutral pH values while no degradation
      occurred at alkaline pH values. Moreover, the degradation was increased at higher
      temperatures. Copper complex act as a catalyst for the polypeptide hydrolysis.
      The protein degradation was protected with beta-mercaptoethanol by acting as
      radical scavenger. H2O2 increased BSA degradation which is apparent by the
      disappearance of the original band. H2O2 reacts with copper complex to produce a
      reactive oxygen species (ROS), such as hydroxyl radical or a metal-coordinated
      oxo or peroxo species, which in turn can initiate cleavage of the peptide
      backbone nearby.

PMID- 14972801
TI  - Support costs of different branch designs: effects of position, number, angle and
      deflection of laterals.
AB  - The structural theory for cantilever beams was used to calculate the dry weight
      of wood that a branch of Picea sitchensis (Bong.) Carr. must produce to support
      its own weight plus that of laterals in different positions and numbers, and with
      different angles and deflections. The endpoint of the branch was maintained at 2%
      of its length, and constant values or functions (measured on real branches) were
      assumed for Young's modulus, taper and self weights of wood and foliage. Support
      costs (branch wood dry weights) were minimized when laterals were positioned so
      that the center of gravity was close to the base of the branch, and when the
      branch was angled upward from the horizontal. Small savings in support costs also
      resulted when laterals were not forward pointing, were angled upward and had
      endpoint deflections of at least 20% of their length.

PMID- 14972802
TI  - Water stress integral-a link between short-term stress and long-term growth.
AB  - Water stress integral (S(Psi)), the cumulative integral of pre-dawn leaf water
      potential over any chosen period of time, was estimated from measurements of pre
      dawn water potential made every two weeks in a Pinus radiata D. Don plantation
      near Canberra, Australia. Also measured were final length of current-season
      needles and annual stem basal area increment. Data were gathered over a 4-year
      period from a control plot, a fertilized plot, an irrigated plot, and two plots
      that were both fertilized and irrigated. Among years and treatments, annual basal
      area increment varied over a threefold range. Of this variation, 91% was
      accounted for by variation in S(Psi) for the entire year, during every month of
      which stem diameter growth occurred. Of variation in annual needle elongation,
      90% was accounted for by variation in S(Psi) from late August to late February,
      which was the period of needle growth. In dry years, the annual value of S(Psi)
      in non-irrigated plots was mainly determined by soil water content, but in wet
      years in non-irrigated plots, and in all years in irrigated plots, it was closely
      correlated with tree nutrient status (r(2) = 0.81).

PMID- 14972803
TI  - Drought tolerance, growth partitioning and vigor in eucalypt seedlings and rooted
      cuttings.
AB  - To clarify the physiological basis of productivity differences among rooted
      cuttings and seedlings of eucalypt species, relationships between morphology and
      water relations were examined in 4-month-old seedlings of Eucalyptus grandis W.
      Hill ex Maiden, E. urophylla S.T. Blake and E. cloeziana F. Muell. and in 4-month
      old rooted cuttings of three E. grandis cultivars. Four-month-old seedlings had
      greater dry weights, lower leaf area/root dry weight (LA/RDW) ratios and lower
      shoot/root dry weight (S/R) ratios than 4-month-old rooted cuttings. For all
      cultivars of E. grandis, tall rooted cuttings, as defined by height at age 4
      weeks, had greater dry weights by age 4 months and lower LA/RDW and S/R ratios
      than short rooted cuttings. There were differences in height growth, dry matter
      productivity and relative shoot and root development among cuttings of different
      E. grandis cultivars, but these differences were not as great as the differences
      between short and tall grades of the same cultivar and between seedlings and
      cuttings. Consistent with the differences in LA/RDW and S/R ratios, seedlings had
      higher daytime water potentials (Psi(x)) than cuttings, and tall cuttings had
      higher daytime values of Psi(x) than short cuttings. Differences in Psi(x) were
      also related to stomatal conductance (g(wv)), which was up to 300% greater in
      short cuttings than in tall cuttings. Among seedlings, those of E. cloeziana,
      which had the smallest dry weight at age 4 months, had the highest g(wv), whereas
      those of E. grandis, which had the greatest dry weight at age 4 months, had the
      lowest g(wv). Unlike seedlings and the tall cuttings, short cuttings lost turgor
      when subjected to drought. The differences observed in susceptibility to water
      stress may account in part for the associated differences in dry matter
      production. Xylem pressure potential and relative water deficit at zero turgor
      did not differ significantly among the types of plants studied, which suggests
      that differences in growth rates were not the result of differences in
      dehydration tolerance.

PMID- 14972804
TI  - Crown architecture and stemwood production in Norway spruce (Picea abies (L.)
      Karst.).
AB  - The morphological data for Norway spruce (Picea abies (L.) Karst.) trees
      published by Burger (1953) were reanalyzed to examine the relationships between
      crown shape, needle and branch mass density of crown volume, needle efficiency in
      stemwood production, harvest index and stemwood production efficiency per unit of
      crown projected area. Production of stemwood per unit of crown projected area was
      higher in narrow-crowned trees than in broad-crowned trees because the narrow
      crowned trees had (i) smaller horizontal space requirements for equal crown
      volumes, (ii) higher leaf area index due to both the geometrical crown shape and
      higher needle density per unit of crown volume, and (iii) higher harvest index
      indicating high allocation of dry matter production to stem.

PMID- 14972805
TI  - Growth, cambial activity and phloem structure in compatible and incompatible
      peach/plum grafts.
AB  - Peach (Prunus persica L. Batsch) shoots grafted onto compatible or incompatible
      clones of rootstocks of myrobolan plum (Prunus cerasifera L. Ehrh. cv. myrobolan)
      were observed in a greenhouse for 100 days after grafting. The incompatible
      grafts showed foliar symptoms of incompatibility and reduced shoot growth about
      60 days after grafting. Light microscopic studies revealed that cambial activity
      stopped earlier in the rootstocks, than in the scions, of incompatible grafts.
      Structural modifications were also observed in the phloem of incompatible grafts.
      Compared with the compatible graft rootstock, the number of sieve elements
      differentiated from the cambial zone was reduced in the incompatible graft
      rootstock, whereas the production of parenchyma cells was not affected. No
      important ultrastructural alteration was observed in the sieve tubes of the
      incompatible grafts. However, osmiophilic granulations near the plasma membrane
      of sieve plates were observed more frequently in the rootstocks of incompatible
      grafts than in ungrafted myrobolan controls. It is concluded that the external
      symptoms of incompatibility are not related to massive structural modifications
      or degeneration of the conducting tissues.

PMID- 14972806
TI  - Soil acidity, and the growth, biomass partitioning and leaf mineral composition
      of honeylocust (Gleditsia triacanthos L.) seedlings.
AB  - Honeylocust seedlings (Gleditsia triacanthos L.) were grown in cylinders
      containing soil adjusted to pH 4, 5 or 6, and harvested every 10 days for 40 days
      for dry weight and leaf mineral analysis. Total weight of plants grown at pH 4
      was less than that of plants grown at pH 5 or 6. Root weight accounted for a
      greater proportion of total weight in plants grown at pH 4 than in plants grown
      at pH 5 or 6. Root growth as a function of total plant growth was higher in
      plants grown at pH 4 than in plants grown at pH 5 or 6, whereas leaf growth as a
      function of total plant growth was less in plants grown at pH 4 than in plants
      grown at pH 5 or 6. However, the relationships between root biomass and root
      length and between leaf biomass and leaf area were the same in all treatments. An
      analysis of total leaf concentrations of Ca, P, K, Mg, Mn and Al indicated that
      Al accumulation in leaves was significantly related to a decrease in plant growth
      at pH 5. A leaf tissue aluminum concentration of 35 microg g(-1) was associated
      with toxicity symptoms and a 25% reduction in total plant weight.

PMID- 14972807
TI  - The influence of glutamine on growth and viability of cell suspension cultures of
      Douglas-fir after exposure to polyethylene glycol.
AB  - The response of cell cultures of Douglas-fir (Pseudotsuga menziesii (Mirb.)
      Franco) to osmotic stress was studied by measuring cell growth and viability
      after exposure to polyethylene glycol (PEG) (M(r) 6000-8000). Growth of cells
      inoculated in a medium containing 10% PEG was slightly inhibited, whereas growth
      in a medium containing 15% PEG was severely inhibited. Cells grown for 6 days in
      nutrient medium and then subcultured in a medium containing 15% PEG to induce
      water stress showed high viabilities, whereas cells grown for longer than 6 days
      before exposure to PEG showed decreased viabilities after subculture. Cells grown
      in medium containing 30 mM glutamine were significantly more resistant to PEG
      induced water stress, as measured by viability, than cells grown in medium
      without glutamine.

PMID- 14972808
TI  - J 16: An apex protein associated with juvenility of Sequoiadendron giganteum.
AB  - Shoot apex proteins from 11 seedlings, two juvenile clones and three mature
      grafted clones of Sequoiadendron giganteum (Lindl.) Buchh. were examined
      throughout the year by SDS-polyacrylamide gel electrophoresis. A membrane
      associated protein known as J 16, with an approximate molecular weight of 16 kD,
      was always detected in juvenile tissue, but was absent in tissue of the mature
      clones. The J 16 protein was also present in extracts of a mature clone that had
      been morphologically rejuvenated by micrografting. Protein extracts from the
      rejuvenated clone, were separated by electrophoresis and assayed for J 16 using
      an immunoblotting procedure with anti-J 16 serum. This test revealed two bands, J
      16 and another protein with a lower molecular weight. The small molecular weight
      protein was not detected in juvenile clones.

PMID- 14972809
TI  - Adaptations to intermittent drying in germinating Eucalyptus sieberi L. Johnson
      seeds and young seedlings.
AB  - Before Eucalyptus sieberi L. Johnson seeds germinate, the protein reserves in a
      small group of cells in the collet are mobilized and the cells swell sufficiently
      to break the seed coat allowing further water uptake. If the seedling is
      desiccated at this stage, the embryo remains viable and when the seed is rewetted
      reserves are mobilized in the cells immediately behind those which expanded
      initially. Mobilization of reserves and subsequent cell elongation occur
      sequentially along the hypocotyl after successive dry periods until the reserves
      are exhausted. Early in the sequence, the distal end of the hypocotyl extends and
      is positively geotropic, whereas at the end of the sequence the proximal end of
      the hypocotyl extends and is negatively geotropic, raising the cotyledons
      rapidly. If the radicle is destroyed or unable to elongate, it is replaced by two
      adventitious roots, one below the petiole of each cotyledon. Indole acetic acid
      and sucrose can substitute for the cotyledons in the production of adventitious
      roots.

PMID- 14972810
TI  - Auxin and ethylene regulation of diameter growth in trees.
AB  - Recent studies on the phytohormonal regulation of seasonal cell-division activity
      in the cambium, primary-wall radial expansion of cambial derivatives,
      differentiation of xylem cells, and growth of the cortex in forest trees of the
      north temperate zone are reviewed. Indol-3-ylacetic acid (IAA, auxin) has been
      characterized by combined gas chromatography-mass spectrometry (GC-MS) in the
      cambial region of Abies balsamea, Pinus densiflora, Pinus sylvestris and Quercus
      robur. All of the evidence supports the hypothesis that developing leaves and
      extending shoots are primary sources of IAA. The rate of ethylene emanation
      varies among conifer species when adjoining phloem and cambial tissues are
      incubated in vitro. The cambium from young cuttings of Abies balsamea produces
      more ethylene than that from older cuttings. Ethylene production by seven-year
      old Abies balsamea cambium is substantially increased in vitro when the tissue is
      provided with exogenous 1-aminocyclopropane-1-carboxylic acid and IAA. In
      response to elevated ethylene concentrations, cortex growth is accelerated in
      both hardwood and conifer seedlings. Ethrel (2-chloroethylphosphonic acid)
      increases ray size and ray-cell number and promotes traumatic resin-canal
      development in xylem. In Ulmus americana, endogenous ethylene concentrations are
      inversely correlated with cambial activity. Ethylene decreases vessel diameter in
      Acer negundo, Acer platanoides and Ulmus americana. Several studies suggest that
      ethylene has a role in regulating reaction-wood formation in both conifers and
      hardwoods.

PMID- 14972811
TI  - A dynamic model for water flow in a single tree: evidence that models must
      account for hydraulic architecture.
AB  - A model is presented for the dynamics of water flow in a single eastern white
      cedar tree (Thuja occidentalis L.). The model takes into account the spatial and
      temporal dependence of the evaporative flux from leaves in the crown. It also
      accounts for the quantitative hydraulic architecture of the tree, i.e., the model
      characterizes the tree as a branched catena of > 4000 stem segments in which
      account is taken of the segment length, diameter, hydraulic resistance, and the
      total area of leaves attached to the segment. Input values needed to run the
      model are measurements of evaporative flux, hydraulic conductance of stems versus
      stem diameter, and leaf and stem water storage capacitances. Output parameters
      are the spatial and temporal characterization of stem and leaf water potentials,
      stem and leaf water deficits, sap flow rate, and relative sap velocity. The input
      and output values of the branched catena model are compared and contrasted to
      that of an unbranched catena model. It is shown that the branched catena model
      fits independently measured field parameters better than an unbranched catena
      model. Close correspondence is found between model predictions and field
      measurements of shoot water potential, pressure gradients in stems, hysteresis in
      sap velocity between the lower and upper parts of the tree, and diurnal changes
      in stem and leaf water deficits. This model is discussed in terms of both the
      hydraulic architecture of trees and the potential application of the model to
      questions of tree morphology, ecology, physiology and evolution.

PMID- 14972812
TI  - Diameters and dry weights of tree shoots: effects of Young's modulus, taper,
      deflection and angle.
AB  - The structural theory for cantilever beams was used to calculate the diameters
      and dry weights of wood that unbranched shoots must produce to support their own
      weights. The study was done on Picea sitchensis (Bong.) Carr., Pinus contorta
      Dougl., Larix decidua Mill. and Betula pendula Roth. syn. verrucosa Ehrh. The
      weights of wood increased in a non-linear fashion with increase in shoot length.
      A large investment in wood (as measured by diameter and dry weight) was required
      to maintain a small endpoint deflection (1-5% of the length). By contrast, the
      degree of linear taper had only a small effect on support costs, as did the
      Young's modulus of the wood (over the range 1-4 GPa) and the angle of the shoot
      from the horizontal (over the range 0-45 degrees ). Current year's shoots on
      young trees of P. sitchensis and P. contorta incur a high support cost in order
      to maintain small (1-5%) deflections throughout the year: similar shoots of L.
      decidua and B. pendula have smaller support costs because they deflect by about
      20% after leaf expansion in spring.

PMID- 14972813
TI  - Control of shoot elongation in ponderosa pine: relative roles of apical and
      axillary meristems.
AB  - Buds of ponderosa pine (Pinus ponderosa var. scopulorum Engelm.) from which the
      shoot apical meristems had been surgically removed elongated normally but did not
      form new terminal buds. Shoot, stem unit and needle growth were similar to those
      of controls. Removal of needle fascicles from buds starting to elongate inhibited
      growth, whether or not the shoot apical meristem had been removed. The length of
      completely defoliated shoots increased by 8.3%, the length of shoots defoliated
      on the upper half increased by 29.6%, and the length of those defoliated on the
      lower half increased by 44.9%. The length of controls increased by 137.4% during
      the same period. On partially defoliated shoots, defoliated stem units elongated
      less than undefoliated ones. Shoots developing from buds enclosed in light-proof,
      aluminum-foil bags elongated normally but apparently lacked chlorophyll.
      Increases in dry weight were significantly correlated with number of stem units
      (r(2) = 0.53). Results suggest that shoot elongation is controlled endogenously.
      This control may be mediated by IAA outputs from axillary meristems proportional
      to meristem number, and the importation of carbohydrates, proportional to the
      output of IAA.

PMID- 14972814
TI  - Nitrate content, amino acid composition and growth of yellow birch seedlings in
      response to light and nitrogen source.
AB  - Yellow birch (Betula alleghaniensis Britt.) seedlings were grown for three months
      in a greenhouse at two radiant flux densities-full light (FL) and 50% shade (LL)
      and with three nitrogen sources- ammonium only (NH(4) (+)), nitrate only (NO(3) (
      )) and a 1:1 mixture of ammonium and nitrate (NH(4) (+)/NO(3) (-))-in a
      completely randomized factorial design. The total biomass of seedlings grown
      under low light (LL) did not vary significantly with nitrogen source; although
      NO(3) (-)-treated seedlings were smaller and had a significantly lower (P </=
      0.05) net assimilation rate (NAR) than NH(4) (+)-, and NH(4) (+)/NO(3) (-)-N
      treated seedlings. Under full light (FL), NW-treated seedlings had a lower leaf
      area ratio (LAR) and a significantly lower total biomass and relative growth rate
      (RGR) than seedlings grown with either NO(3) (-) or NH(4) (+)/NO(3) (-). Under
      LL, nitrate concentrations in xylem sap and leaves of plants grown with NO(3) (-)
      or NH(4) (+)/NO(3) (-) were many times greater than under FL. Amino acid profiles
      were affected by nitrogen source but were not affected by radiant flux density.
      When NH(4) (+)-N was absent from the nutrient solution, the percentage of NH(2)-N
      carried in the xylem sap decreased for aspartic acid but increased for alanine
      and glycine. The results indicate that it is the initial reduction of NO(3) (-)
      in roots, rather than the later stages of amino acid synthesis, that is limited
      by light in yellow birch seedlings.

PMID- 14972815
TI  - Long-term elevation of atmospheric CO(2) concentration and the carbon exchange
      rates of saplings of Pinus taeda L. and Liquidambar styraciflua L.
AB  - The relationship between carbon exchange rate (CER) and internal CO(2)
      concentration was measured in leaves of saplings of Liquidambar styraciflua L.
      (sweetgum) and Pinus taeda L. (loblolly pine) grown from seed for more than 14
      months at atmospheric CO(2) concentrations of either 350 or 500 microl l(-1). An
      elevated concentration of CO(2) during growth reduced CER at any given internal
      CO(2) concentration in sweetgum, but not in loblolly pine. Stomatal limitation of
      CER showed little response to concentration of CO(2) during measurement, but was
      higher in both species when grown at 500 than at 350 microl l(-1) CO(2). The net
      effect of a long-term increase in CO(2) concentration from 350 to 500 microl l(
      1) was an increase in CER of loblolly pine, but a slight decrease in CER of
      sweetgum. It is suggested that the depression of CER in sweetgum resulted from a
      reduction in the activity of ribulose-1,5-bisphosphate carboxylase-oxygenase.

PMID- 14972816
TI  - Comparative water relations of three successional hardwood species in central
      Wisconsin.
AB  - Water relations of co-occurring understory saplings of Quercus ellipsoidalis E.J.
      Hill, an early successional, xeric species, Populus tremuloides Michx., an early
      successional, mesic species, and Acer rubrum L., a late successional species that
      occurs on both wet and dry sites, were evaluated on four dates during the 1986
      growing season. The understory was characterized by high soil water content, low
      irradiance and low vapor pressure deficit throughout the growing season. Stomatal
      conductance and calculated transpiration flux were lowest for A. rubrum and
      highest for P. tremuloides and Q. ellipsoidalis. Except early in the growing
      season, leaf water potentials were lower in P. tremuloides than in the other
      species. Populus tremuloides had the highest bulk modulus of elasticity, Q.
      ellipsoidalis the lowest. Over the growing season, Populus tremuloides and Q.
      ellipsoidalis, but not A. rubrum, exhibited a decrease in osmotic potential at
      both full and zero turgor. Of the three species, Populus tremuloides exhibited
      the sharpest decrease in leaf water potential and turgor pressure with decreasing
      relative water content.

PMID- 14972817
TI  - Boron fertilization and carbohydrate relations in mycorrhizal and nonmycorrhizal
      shortleaf pine.
AB  - Eight-week-old shortleaf pine seedlings (Pinus echinata Mill.) with and without
      ectomycorrhizae formed by Pisolithus tinctorius were treated for two to eight
      weeks with 25 microg borate ml(-1) solution applied either to the soil, or as a
      foliar spray, or in both ways. Control seedlings were fertilized only with
      modified Hoagland's solution containing 0.03 microg ml(-1) borate. Five sugars
      (pinitol, fructose, glucose, myoinositol and sucrose) were quantitated in both
      mycorrhizal and nonmycorrhizal roots by gas-liquid chromatography. Fertilization
      with boron increased the total carbohydrate content of mycorrhizal roots except
      in seedlings receiving foliar applications of boron. Foliar + soil fertilization
      yielded a 24% increase in total carbohydrates in mycorrhizal roots, whereas
      foliar fertilization alone decreased the total carbohydrate content. Carbohydrate
      content of nonmycorrhizal roots was significantly increased only by soil
      fertilization with boron. Individual sugars were affected less by boron
      fertilization in nonmycorrhizal roots than in ectomycorrhizal roots. However,
      significant increases in sugars in response to boron fertilization were observed
      in both ectomycorrhizal and nonmycorrhizal plants.

PMID- 14972818
TI  - Factors affecting in vitro propagation of Quercus robur L.
AB  - Explants from five clones of Quercus robur (three of juvenile origin and two from
      adult trees) were cultured on Gresshoff and Doy medium supplemented with 0.2 mg
      l(-1) 6-benzylaminopurine. Shoot proliferation from apical and nodal segments was
      influenced by both clone and type of explant. To increase the efficiency of the
      propagation procedure, donor shoots (20-25 mm in length and with 2 mm removed
      from the tip) were recultured at 4-week intervals, and the newly formed shoots
      harvested before each transfer. Under this regime, the multiplication coefficient
      (proportion of explants forming axillary shoots multiplied by the mean number of
      new 8-mm stem segments per explant) was greatest for the second crop and declined
      sharply by the fourth or fifth crop, in three of the four clones tested.
      Successive additions of fresh liquid medium to old cultures was much less
      effective than transfer to fresh medium in promoting axillary shoot production.
      Elongation of shoots before rooting was increased significantly (P < 0.05) in one
      of two clones tested by transfer to a medium containing either 0.1 or 1.0 mg l(
      1) of zeatin. Addition of fresh liquid medium containing zeatin to old cultures
      failed to improve shoot elongation or axillary shoot production. However,
      treatment for 15 days with liquid medium containing 0.1 or 1.0 mg l(-1) indol-3
      yl-acetic acid increased subsequent rooting.

PMID- 14972819
TI  - Organogenesis and embryogenesis in mature zygotic embryos of Picea sitchensis.
AB  - Differentiation of adventitious buds and somatic embryos from mature zygotic
      embryos of Picea sitchensis (Bong.) Carr. is described. Adventitious buds were
      formed on embryos pulse-treated with 250 microM benzyladenine for 2 h and
      cultured on medium lacking growth regulators. Buds were initiated at different
      frequencies and sites depending on when the BA-pulsed embryos were transferred to
      fresh culture medium. Embryogenic callus was formed when the zygotic embryos were
      cultured on medium containing 10 microM 2,4-dichlorophenoxyacetic acid and 5
      microM benzyladenine. Although 50% of the embryos gave rise to embryogenic
      callus, only 20% of the callus continued to proliferate after subculture.
      Proliferation of new somatic embryos occurred from both the embryonic region and
      the suspensor region on previously formed somatic embryos. The pattern for
      development of adventitious buds and somatic embryos in Picea sitchensis is
      compared to that in Picea abies under similar culture conditions.

PMID- 14972820
TI  - Root growth in Sitka spruce and Douglas-fir transplants: dependence on the shoot
      and stored carbohydrates.
AB  - When dormant Sitka spruce (Picea sitchensis (Bong.) Carr.) transplants were
      lifted from the nursery in March and transferred to favorable growing conditions
      in a controlled environment chamber, new roots emerged and elongated even when
      the plants were bark-ringed so that the roots could not receive metabolites from
      the shoot by phloem translocation. Carbohydrate analysis showed that starch
      reserves in the roots of the bark-ringed plants were depleted, indicating that
      these reserves provided the energy source for new root growth. The shoot also had
      a role in new root growth as excised root systems showed greatly reduced root
      growth. This response is compared to that of Douglas-fir (Pseudotsuga menziesii
      (Mirb.) Franco) in which bark-ringing prevented root growth indicating that
      current photosynthate is needed for new root growth. The findings are discussed
      in relation to the problems of establishing these species in forest plantations.

PMID- 14972821
TI  - The activity, characterization and distribution of the nitrogen assimilation
      enzyme, glutamine synthetase, in jack pine seedlings.
AB  - The extraction of glutamine synthetase (GS) from jack pine (Pinus banksiana
      Lamb.) tissue was facilitated by solubilization of the tissue with 1% or more
      Nonidet P-40 detergent. In contrast with procedures commonly used to extract GS
      from other plant tissues, highest recovery of GS was obtained when jack pine
      tissues were subjected to ultrasonic homogenization in the absence of PVP.
      Chromatography on DEAE-Sephacel showed that jack pine needles possess two
      isoforms of GS. Isoform GS(1), which is generally associated with the cytoplasm,
      eluted at 90 mM KCl and accounted for 80% of total GS activity. Isoform GS(2),
      which eluted at 280 mM KCl, is generally associated with the chloroplast and is
      thought to be active in the primary assimilation of ammonium in leaves. Thus
      GS(2) activity may be important if conifers are to avoid ammonium toxicity under
      circumstances, such as exposure to nitrous oxides, where nitrate reductase
      activity is induced in needles. In June, 72% of total GS activity was located in
      needles. Near the end of the growing season in August, however, only 1% of total
      GS activity was found in needles whereas 79% was found in roots.

PMID- 14972822
TI  - Autumnal changes of sulfur fractions and the ratio of organic sulfur to total
      nitrogen in leaves and adjacent bark of eastern cottonwood, white basswood and
      actinorhizal black alder.
AB  - Autumnal changes in organic-S, sulfate-S, total-S and the ratios of organic-S to
      total-N and sulfate-S to organic-S were followed in leaves and adjacent bark of
      actinorhizal (Frankia-nodulated) black alder (Alnus glutinosa (L.) Gaertn.) and
      eastern cottonwood (Populus deltoides Bartr. ex Marsh.) trees growing on a
      minespoil site high in extractable soil sulfate, and in black alder and white
      basswood (Tilia heterophylla Venten.) trees growing on a prairie-derived soil in
      Illinois. Organic-S concentrations decreased significantly (P < 0.05) during
      autumn only in foliage of trees growing on the prairie-derived soil where losses
      of leaf organic-S were 65% for black alder and 100% for white basswood. Leaf
      sulfate concentrations were relatively stable throughout autumn in white basswood
      growing on prairie-derived soil and in black alder at both sites. Sulfate-S
      concentrations in leaves were significantly (P < 0.05) higher in trees at the
      minespoil site than in trees growing in the prairie-derived soil (5.1 mg g(-1)
      for the minespoil site and 1.2 mg g(-1) for the prairie-derived soil), and in the
      non-actinorhizal species during late summer. During the autumn, the ratio of
      organic-S to total-N doubled in leaves of eastern cottonwood at the minespoil
      site, but in black alder and white basswood growing on the prarie-derived soil,
      it decreased by 60 and 74%, respectively. Organic-S concentrations in bark
      increased more during autumn in species unable to fix atmospheric N(2), than in
      black alder. The results suggest that patterns of autumnal translocation of leaf
      S can be site-dependent and that leaf S and leaf N are, at least in part,
      translocated independently in the fall. Black alder and eastern cottonwood seemed
      to incorporate sulfate-S readily into organic substances in leaves when grown in
      soils with a high sulfate content.

PMID- 14972823
TI  - Growth and water relations of seedlings of two subspecies of Eucalyptus globulus.
AB  - Seedlings of Eucalyptus globulus Labill subsp. globulus grown in soil in pots in
      the greenhouse grew faster than seedlings of E. globulus subsp. bicostata, and
      responded better to added nutrients and water. However, water stress caused a
      greater reduction in the growth of shoots and roots, and in the root/shoot ratios
      of fertilized seedlings of subsp. globulus than in those of bicostata. More leaf
      surface wax was produced by seedlings grown in the presence of fertilizer and an
      adequate supply of water than by seedlings subjected to nutrient or water stress.
      Despite larger amounts of leaf surface wax, seedlings of subsp. bicostata had
      higher epidermal conductances than seedlings of subspecies globulus. However,
      epidermal conductances were reduced more by water stress and by fertilization in
      seedlings of subsp. bicostata than in subsp. globulus. Tissue osmotic potentials
      at full and zero turgor were reduced by water stress only in seedlings of subsp.
      bicostata and were increased by fertilizer only in seedlings of subsp. globulus.
      The results indicate that although seedlings of subsp. globulus have inherently
      higher growth rates, seedlings of subsp. bicostata are better adapted to drought.

PMID- 14972824
TI  - Growth and development during the establishment year of two Populus clones with
      contrasting morphology and phenology.
AB  - Weekly morphological measurements of trees in permanent growth plots and periodic
      destructive sampling were used to monitor growth and development of two Populus
      clones with contrasting morphology and phenology during the establishment year in
      a short-rotation, intensive-culture system. Tristis (P. tristis Fisch. x P.
      balsamifera L.) grew rapidly for 48 days before setting bud in July. By contrast,
      Eugenei (P. x euramericana (Dode) Guinier) grew at a slower rate than Tristis,
      but maintained this rate for 75 days before setting bud in September. By early
      October, the total leaf area and dry weight of Eugenei exceeded that of Tristis
      by 39 and 11%, respectively. In addition, Eugenei had a greater harvest index
      than Tristis throughout most of the growing season because a larger proportion of
      photosynthate produced was directed to shoot growth; however, a high shoot/root
      ratio in Eugenei predisposed it to water stress. Differences in aboveground
      biomass between clones were largely attributable to clonal differences in
      seasonal leaf area development.

PMID- 14972825
TI  - Effects of hypoxia and elevated carbon dioxide concentration on water flux
      through Populus roots.
AB  - Restricted gas exchange between the rhizosphere and aerial environment reduces
      the concentration of oxygen (O(2)) and elevates the concentration of carbon
      dioxide (CO(2)) in the root zone, thereby leading to increased resistance to root
      water uptake. In this study, the effects of hypoxia and 20% CO(2) on water flux
      (J(v)) through roots of hybrid poplar (Populus trichocarpa Torr. & A. Gray x P.
      deltoides Bartr. ex Marsh) were measured in detached root systems under pressure
      in solution culture. Because stomata closed and there was no change in foliar
      water potential in hypoxic plants, root resistance was measured in detached
      systems as opposed to using whole plant measurements. However, under aerated
      conditions root resistance values were similar in intact plants and excised
      roots. Water fluxes through pressurized root systems treated with nitrogen and
      low oxygen (< 2% O(2)), elevated CO(2) (20% CO(2)), and low O(2) with elevated
      CO(2) concentrations were reduced to 40, 51 and 58%, respectively, of J(v) of
      plants aerated with ambient air. Reductions in J(v) occurred more rapidly in
      response to elevated CO(2) than to low O(2) concentrations. The effects of low
      O(2) and elevated CO(2) were not additive. Changes in pH that resulted from
      elevated CO(2) concentrations did not account for the reduction in J(v). When
      root systems of intact plants were pretreated for 24 or 48 h with low O(2)
      concentration, J(v) measured on pressurization was reduced by 33 and 48%,
      respectively, compared to aerated roots. Stomatal conductance was also reduced,
      however, so leaf water potential of plants with hypoxic roots were similar to
      those of aerated controls.

PMID- 14972826
TI  - Sensitivity of red oak (Quercus rubra L.) and American beech (Fagus grandifolia
      Ehrh.) seedlings to sodium salts in solution culture.
AB  - Sodium salt sensitivity of red oak (Quercus rubra L.) and American beech (Fagus
      grandifolia Ehrh.) was evaluated in solution culture. Both species showed
      symptoms of salt injury when grown in the presence of less than 10 mM Na. In red
      oak, leaf symptoms first appeared at a sodium concentration of 6.0 mM and leaf
      weight was significantly reduced at 7.5 mM Na. Leaf, stem and root dry weights of
      American beech were significantly reduced in the presence of 4.0 mM sodium. In
      both species, browning of leaf margins and necrosis were evident in the Na
      treated plants. The observed symptoms were associated with high concentrations of
      sodium in the tissues. Neither species appears to have control over sodium uptake
      and translocation.

PMID- 14972827
TI  - Micropropagation of a mature colchicine-polyploid and irradiation-mutant of
      Betula pendula Roth.
AB  - Tetraploid plantlets were regenerated from cultured apical and axillary buds of a
      23-year-old colchicine-polyploid and irradiation-mutant Betula pendula Roth tree.
      Bud explants were grown on modified Murashige and Skoog medium supplemented with
      2.0 mg l(-1) benzylaminopurine (BAP) and 0.01 mg l(-1) 1-naphthaleneacetic acid
      (NAA). The medium allowed both induction of adventitious buds and development of
      shoots. The cut ends of new shoots produced new buds and shoots during a 4-week
      culture period. The micropropagated shoots were rooted on modified Murashige and
      Skoog medium containing 0.1 mg l(-1) NAA as the sole growth regulator. Plantlets
      were transferred to a peat/soil mixture (1:1) in the greenhouse, acclimated and
      then transplanted to a cold frame. The regenerated plantlets had a tetraploid
      chromosome set (4n = 56) and an altered leaf morphology typical of colchicine
      polyploid birches. The leaves were hypertrophied and asymmetrical, with curly
      leaf margins. The mutant nature of the parent tree was also evident in the light
      green color of the leaves of the plantlets.

PMID- 14972828
TI  - Protein synthesis in slash pine callus cultures exposed to water stress.
AB  - Effects of water stress on protein synthesis were investigated in heterotrophic
      callus cultures derived from slash pine (Pinus elliottii Engelm.) cotyledon
      explants. Cultures were transferred to medium containing 0-15% mannitol to
      provide water potentials between -0.4 and -2.5 MPa. Beginning between 0 and 22 h
      after transfer to the new medium, cultures were incubated for 2 h with (35)S
      methionine. Both the uptake of label and the incorporation of label into protein
      decreased with decreasing medium water potential. Incorporation, however, was
      reduced to a greater extent than uptake suggesting that the reduced incorporation
      was at least partly the result of reduced protein synthesis. Separation of
      labeled proteins by one-dimensional SDS-polyacrylamide gel electrophoresis and
      visualization by fluorography revealed the induction of two new protein bands
      after incubation at -1.8 MPa for 24 h. Induction of new proteins was not observed
      at other water potentials or after shorter incubation times. Protein bands from
      cultures incubated at -1.8 MPa for 24 h and then transferred for 24 h to mannitol
      free medium (-0.4 MPa) were comparable to those from control cultures maintained
      on mannitol-free medium throughout.

PMID- 14972829
TI  - Chlorophyll and carotenoid concentrations in two varieties of Pinus ponderosa
      seedlings subjected to long-term elevated carbon dioxide.
AB  - Two varieties of ponderosa pine (Pinus ponderosa Dougl. var. scopulorum (Rocky
      Mountain variety) and P. ponderosa var. ponderosa (Sierran variety)) seedlings
      were subjected to elevated atmospheric CO(2) for two and a half years. The CO(2)
      concentrations were ambient, ambient + 75 microl l(-1), ambient + 150 microl l(
      1) and ambient + 300 microl l(-1), or approximately 350, 425, 500 and 650 microl
      l(-1) CO(2). After one and a half years of exposure to elevated CO(2) and until
      the end of the study, seedlings of both varieties showed symptoms of stress
      including mottling, mid-needle abscission and early senescence. In both
      varieties, exposure to CO(2) concentrations greater than ambient + 75 microl l(
      1) resulted in lower chlorophyll a, chlorophyll b and carotenoid concentrations.
      At elevated CO(2) concentrations, the concentrations of pigments in needles of
      the Sierran variety were lower than those in the Rocky Mountain variety. Also, at
      elevated CO(2) concentrations, the pigment concentrations in the 1-year-old
      needles of both P. ponderosa varieties were lower than those in current-season
      needles.

PMID- 14972830
TI  - Seasonal changes in levels of cytokinin-like compounds from Douglas-fir xylem
      extrudate.
AB  - High-performance liquid chromatography, immunochromatography, and
      radioimmunoassay were used to identify cytokinin-like bases and glycosides in
      xylem sap of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco).
      Isopentenyladenosine-type (isopentenyladenine and isopentenyladenosine) and
      zeatin-riboside type (zeatin, zeatin riboside, and dihydrozeatin riboside)
      cytokinins were detected during springtime. A glucosyl conjugate of zeatin
      riboside was also present in small amounts. Levels of cytokinin-like compounds
      varied throughout the spring but were generally highest in late April to early
      May.

PMID- 14972831
TI  - Cytokinins in the root pressure exudate of Citrus jambhiri Lush. colonized by
      vesicular-arbuscular mycorrhizae.
AB  - The influence of vesicular-arbuscular mycorrhizal (VAM) symbiosis on the
      transport of cytokinins from the root to the shoot of Citrus jambhiri Lush.
      seedlings inoculated with cultures of Glomus etunicatum (Becker and Gerd.), G.
      fusciculatum (Thaxt.) Gerd. and Trappe, or G. mosseae (Nichol. and Gerd.) was
      investigated. Cytokinins collected from root exudates over a 90-day period were
      analyzed by high-performance liquid chromatography, mass spectrometry and a
      bioassay. The flux of cytokinins was independent of root exudate flux. Seedlings
      inoculated with G. fasciculatum or G. mosseae yielded a greater flux of zeatin,
      dihydrozeatin and zeatin riboside than non-inoculated seedlings. The flux of
      zeatin riboside was significantly greater than the flux of zeatin in seedlings
      inoculated with VAM symbionts. Vesicular-arbuscular mycorrhizal relationships
      apparently contributed to, or influenced, the export of cytokinins from the root.
      The elevated cytokinin flux of inoculated seedlings was associated with improved
      tissue phosphorus nutrition and a significant increase in seedling biomass.

PMID- 14972832
TI  - Inhibition of protein synthesis in loblolly pine hypocotyls by mannitol-induced
      water stress.
AB  - The relationship between mannitol-induced water stress and protein synthesis was
      investigated in hypocotyl slices of loblolly pine (Pinus taeda L.). Mannitol
      induced water stress inhibited the incorporation of L-[(35)S]methionine into
      protein. As the water potential decreased, incorporation of label into protein
      decreased in both the soluble- and membrane-protein fractions. There were no
      significant differences in response to water stress among seed sources from four
      different geographical regions.

PMID- 14972833
TI  - Factors influencing germination and establishment of Eucalyptus pauciflora near
      the alpine tree line.
AB  - Factors affecting seed germination, seedling establishment and growth to
      reproductive maturity in Eucalyptus pauciflora Sieb. ex Spreng. at the tree line
      in southeastern Australia were investigated. Timing of germination was determined
      principally by temperature but could be strongly modified by soil water.
      Mortality of germinants was heaviest during the first growing season (dependent
      on soil water) and the first winter (dependent on the depth and duration of snow
      cover). Neither plant nor soil treatments with insecticide or fungicide had an
      overriding or consistent effect on germination or seedling establishment. The
      probability of reaching the sapling stage was greater for planted seedlings than
      for plants germinated on site, indicating the dependence of survival on
      accumulated reserves. There was no clear indication of a general decrease in
      survival with increasing altitude, because of an interplay between elevation and
      site factors including competing vegetation, snow depth and period of snow cover.
      Five-year-old saplings planted up to 200 m above the tree line produced
      reproductive structures and viable seed between the ages of 13 and 18 years. The
      relevance of the results to an understanding of the location of the present tree
      line is discussed.

PMID- 14972834
TI  - Water relations of Eucalyptus pauciflora near the alpine tree line in winter.
AB  - Water potential measurements were made, over three winter seasons, on Eucalyptus
      pauciflora Sieb. ex Spreng. at four elevations extending up to 200 m above the
      natural tree line in the Snowy Mountains area of southeastern Australia. Shoot
      water potentials were lowest in winter but never approached lethal levels.
      Contrary to expectations, there was no gradient of water potential with
      elevation. This was attributed primarily to the absence of a gradient of soil
      temperatures once snowpack had developed. Lowest water potentials were observed
      at air temperatures several degrees above zero, suggesting that transpiration and
      absorption may be differently affected, with temperatures above and below these
      values causing higher water potentials. The results suggest that shoot dieback in
      winter, which is a common phenomenon at alpine tree lines, is not caused by low
      water potentials in southeastern Australia.

PMID- 14972835
TI  - Lateral bud outgrowth on decapitated shoots of low-pruned mulberry (Morus alba
      L.).
AB  - After decapitation, lateral shoot growth of mulberry coppice (Morus alba L. cv.
      Shin-ichinose) from 10-year-old stumps had an extremely acrotonic form compared
      with that of intact one-year-old stems of trees during the spring. When one
      dominant shoot from each stump was decapitated, only a few upper lateral buds
      grew out and elongated. Defoliation of the decapitated shoots resulted in an
      increase in the number of shoots sprouting and a decrease in the rate of
      elongation of the laterals. Further enhancement of laterals on decapitated
      dominant shoots resulted from the removal of competing intact coppice shoots from
      the stumps. 1-Naphthaleneacetic acid (NAA) applied as a spray reduced the number
      of lateral buds sprouting from both defoliated, decapitated erect shoots and
      intact horizontally trained shoots. The results suggest that management of
      mulberry coppice could increase the supply of leaves for commercial silk
      production.

PMID- 14972836
TI  - Differential physiological and morphological responses of two hybrid Populus
      clones to water stress.
AB  - Hardwood cuttings of Populus clones Tristis #1 and Eugenei were grown in pots in
      a controlled environment chamber to observe early patterns of growth and water
      relations in response to changing conditions of water stress. Height and dry
      weight growth, dry matter partitioning, leaf area production, stomatal
      conductance and leaf water potential were measured periodically during the 73-day
      experiment. The two clones reacted in a similar way to an initial period of
      stress, showing reduced growth, stomatal conductance and leaf water potential.
      However, when stress was interrupted by ample watering and then reimposed,
      substantial differences between the clones were evident. Growth of Eugenei fully
      recovered after stress was relieved, especially leaf growth, but when water
      deficiency was reimposed, the plants wilted and some leaves died. Tristis #1, in
      contrast, showed a greater adaptation to changing stress conditions; it grew less
      than Eugenei after drought was interrupted, but showed little adverse effect of
      renewed water deficits. These responses were partially explained by the higher
      root/leaf weight ratios of Tristis #1 which enabled it to maintain a more
      favorable plant water status than Eugenei.

PMID- 14972837
TI  - Planting stress in newly planted jack pine and white spruce. 1. Factors
      influencing water uptake.
AB  - Bareroot jack pine (Pinus banksiana Lamb.) seedlings (2 + 0) and bareroot white
      spruce (Picea glauca (Moench) Voss) transplants (1 1/2 + 1 1/2) were taken from
      cold storage and planted on a clearcut forest site in northeastern Ontario on
      several dates between May 6 and June 5 during which period soil temperature at 15
      cm depth increased from 0 to 18 degrees C. Additional cold-stored trees were
      transferred to a greenhouse where they were grown in pots for 0, 7 or 28 days and
      then placed with their roots in aerated water maintained at one of a range of
      constant temperatures between 0 and 22 degrees C. In both species, daytime xylem
      pressure potentials (Psi(x)) and needle conductances (g(wv)) decreased with
      decreasing soil or water temperature. At all root temperatures, g(wv) was lower,
      and Psi(x) higher, in jack pine than in white spruce. After 28 days in the
      greenhouse, g(wv) of jack pine seedlings, and Psi(x) of white spruce, was higher
      than in plants just removed from cold storage. In both species, water-flow
      resistance through the soil-plant-atmosphere continuum (RSPAC) increased as root
      temperature decreased. At all root temperatures, RSPAC was higher in plants just
      removed from cold storage than in plants grown in the greenhouse for 28 days,
      during which time many new unsuberized roots were formed. At root temperatures
      above 10 degrees C, RSPAC of both species was higher in trees newly planted in
      mineral soil than in trees with roots in aerated water; presumably because the
      roots of planted trees had limited hydraulic contact with the soil. On the day
      following removal from cold storage, relative plant water flow resistance
      increased, in both species, more rapidly with declining root temperature than
      could be accounted for by the change with temperature in the viscosity of water,
      thus indicating an effect of temperature on root permeability. The same effect
      was evident in jack pine seedlings, but not white spruce transplants, that had
      been grown for 28 days in the greenhouse after removal from cold storage.

PMID- 14972838
TI  - Planting stress in newly planted jack pine and white spruce. 2. Changes in tissue
      water potential components.
AB  - Water relations of bare-root jack pine (Pinus banksiana Lamb.) and white spruce
      (Picea glauca (Moench) Voss) planted in a greenhouse and on a boreal cut-over
      site were examined during the first growing season. In field-planted trees,
      maximum stomatal conductances (g(wv)) were initially low (< 0.10 cm s(-1)). Base
      and minimum xylem pressure potentials (Psi(x(base)) and Psi(x(min))) were less
      than -1.5 and -1.7 MPa for jack pine and -2.0 and -2.6 MPa for white spruce,
      respectively. During the growing season, maximum g(wv) increased in both species
      to around 0.2 cm s(-1). Base and minimum xylem pressure potentials also increased
      in both species to around -0.5 and -1.0 MPa in jack pine and -1.0 and -1.5 MPa in
      white spruce, respectively. Minimum xylem pressure potentials in white spruce
      fell below the turgor loss point during the first half of the growing season.
      Osmotic potential at the turgor loss point Psi(pi(TLP)) decreased after field
      planting to around -2.7 and -2.3 MPa in jack pine and white spruce, respectively.
      In the greenhouse, minimum values of Psi(pi(TLP)) were -2.2 and -2.3 MPa in jack
      pine and white spruce, respectively. Maximum bulk modulus of elasticity was
      greater in white spruce and underwent greater seasonal change than in jack pine.
      Relative water content (RWC) at turgor loss ranged between 71 and 74% in jack
      pine and 80 and 87% in white spruce. Available turgor (T(avail)), defined as the
      integral of turgor over the range of RWC between Psi(x(base)) and xylem pressure
      potential at the turgor loss point, was similar in jack pine and white spruce
      just after field planting. For the rest of the growing season, however, T(avail)
      in jack pine was two to three times that in white spruce. Diurnal turgor
      (T(diurnal)), defined as the integral of turgor over the range of RWC between
      Psi(x(base)) and Psi(x(min)), as a percent of T(avail) was higher in field
      planted white spruce than jack pine until the end of the season. Dynamics of
      tissue water potential components are discussed in relation to plantation
      establishment.

PMID- 14972839
TI  - Micropropagation and tissue culture of Eucalyptus-a review.
AB  - Micropropagation has the potential to provide very high multiplication rates of
      selected tree genotypes, with resulting short-term silvicultural gains. Aseptic
      cultures have been established from seeds, seedlings, shoots, flowers and
      lignotubers. Callus cultures have been established from a wide range of tissue
      sources for at least 30 species of Eucalyptus. Plant regeneration from callus was
      successful for 12 of these species. Micropropagation through axillary
      proliferation, or adventitious shoot proliferation on nodal explants, or both,
      has been successful. An agar-based medium of Murashige and Skoog with a low
      auxin/cytokinin ratio is most commonly used for shoot multiplication.
      Vitrification and shoot senescence remain problems. Gibberellic acid was added in
      some media to stimulate shoot elongation. Various media are used for in vitro
      root initiation. Suspension and protoplast cultures have been achieved and plants
      have been regenerated from protoplasts. In vitro techniques are presently being
      applied to Eucalyptus to achieve genetic transformations.

PMID- 14972840
TI  - Slash pine bud dormancy as affected by lifting date and root wrenching in the
      nursery.
AB  - Bud dormancy of root wrenched and unwrenched slash pine (Pinus elliottii Engelm.)
      seedlings growing in a forest nursery was measured on five lifting dates.
      Determination of bud dormancy was based on days to budbreak (DBB) under optimal
      growing conditions, mitotic activity in the apical meristem, chilling hours
      accumulated, and bud morphology. Based on DBB, seedlings were most dormant at
      Lift 2 on November 24 after exposure to 189 hours below 10 degrees C and 93 hours
      below 6.7 degrees C. Mitotic activity in the apical meristem was at its lowest 23
      days later at Lift 3, possibly indicating the period when seedlings are most
      resistant to transplanting stresses. Multiple wrenching resulted in a slight
      shift in the dormancy cycle as wrenched seedlings set bud sooner in the nursery
      and broke bud sooner at the planting site in the spring than control seedlings.
      This implies that wrenched seedlings can be successfully lifted from the nursery
      earlier and will initiate spring shoot growth earlier than control seedlings.

PMID- 14972841
TI  - Control of growth of juvenile leaves of Eucalyptus globulus: effects of leaf age.
AB  - Biophysical variables influencing the expansion of plant cells (yield threshold,
      cell wall extensibility and turgor) were measured in individual Eucalyptus
      globulus leaves from the time of emergence until cessation of growth. Leaf water
      relations variables and growth rates were determined as relative humidity was
      changed on an hourly basis. Yield threshold and cell wall extensibility were
      estimated from plots of leaf growth rate versus turgor. Cell wall extensibility
      was also measured by the Instron technique, and yield threshold was determined
      experimentally both by stress relaxation in a psychrometer chamber and by
      incubation in a range of polyethylene glycol solutions. Once emerging leaves
      reached approximately 5 cm(2) in size, increases in leaf area were rapid
      throughout the expansive phase and varied little between light and dark periods.
      Both leaf growth rate and turgor were sensitive to changes in humidity, and in
      the longer term, both yield threshold and cell wall extensibility changed as the
      leaf aged. Rapidly expanding leaves had a very low yield threshold and high cell
      wall extensibility, whereas mature leaves had low cell wall extensibility. Yield
      threshold increased with leaf age.

PMID- 14972842
TI  - A simple method for measuring acetylene reduction of intact, nodulated black
      locust seedlings.
AB  - A simple method is described for measuring acetylene (C(2)H(2)) reduction of
      nodulated black locust (Robinia pseudoacacia L.) seedlings. The C(2)H(2)
      reduction chamber consists of a standard plant pot sealed at one end with a
      stopper having holes for the seedling and a gas inlet port, and sealed at the
      other end with a stoppered collar with a gas port. The chamber temperature is
      regulated by circulating water at a controlled temperature through a copper coil
      surrounding the plant pot. A pump recirculates an approximately ten percent
      C(2)H(2) atmosphere through the system. Nine-week-old black locust seedlings,
      grown in sand culture and inoculated with Rhizobium, were used to obtain ethylene
      (C(2)H(4)) production curves. Ethylene production was linear for up to 60 minutes
      indicating that, for this particular symbiosis, (1) a simple closed system is
      adequate and (2) a short duration assay (10 minutes) will reliably estimate
      C(2)H(2) reduction over a longer period (up to at least 60 minutes). The water
      content of the soil medium had no influence on the C(2)H(2)/(C(2)H(2) + C(2)H(4))
      ratio, which supports the suitability of C(2)H(2) as an internal standard for
      calculating C(2)H(2) reduction. This system has several desirable features.
      First, plant disturbance is minimized. Second, plants can be grown in inexpensive
      pots and no transplanting is necessary. Third, gas exchange and mixing are
      facilitated by a recirculating pump. Finally, root and nodule temperature can be
      controlled.

PMID- 14972843
TI  - Allometry of acetylene reduction and nodule growth of Robinia pseudoacacia
      families subjected to varied root zone nitrate concentrations.
AB  - The effects of nitrate (NO(3) (-)) on acetylene reduction and growth were
      examined in nodulated seedlings from three open-pollinated families of black
      locust (Robinia pseudoacacia L.) grown in sand culture. In the first study, nine
      week-old seedlings were supplied with 0.0, 0.5, 1.0, 5.0 or 15.0 mM NO(3) (-),
      for two weeks during which acetylene reduction and biomass were measured five
      times. In the second study, eight-week-old seedlings were supplied with 0.0, 1.0
      or 5.0 mM NO(3) (-) for 51 days during which acetylene reduction and biomass were
      measured six times. Results were analyzed with and without adjustments for
      seedling size. In the first study, 15.0 mM NO(3) (-) significantly decreased
      total acetylene reduction but lower concentrations did not. In seedlings given
      15.0 mM NO(3) (-), both nitrogenase activity and nodule biomass were reduced.
      Inhibition of nitrogenase activity by NO(3) (-) was reversible. In the second
      study, both the 1.0 and 5.0 mM NO(3) (-) treatments increased plant growth
      compared to the control (0.0 mM). At the end of the 51-day treatment period,
      total acetylene reduction and nodule biomass were greatest in the 1.0 mM NO(3) (
      ) treatment and least in the 5.0 mM NO(3) (-) treatment. However, when adjusted
      for seedling size, total acetylene reduction and nodule biomass were similar in
      the 0.0 and 1.0 mM NO(3) (-) treatments. The greater total acetylene reduction
      and nodule biomass of seedlings grown with 1.0 mM NO(3) (-) resulted from
      increased seedling size due to fertilization. After adjustment for plant size,
      total acetylene reduction, nodule biomass and nitrogenase activity were
      significantly lower in the 5.0 mM NO(3) (-) treatment compared with the control
      or 1.0 mM NO(3) (-) treatment. Adjustment for seedling size, by means of
      allometric principles, appears necessary to interpret treatment effects on total
      acetylene reduction and its components, nodule biomass and nitrogenase activity
      correctly.

PMID- 14972844
TI  - Foliage dark respiration in Abies amabilis (Dougl.) Forbes: variation within the
      canopy.
AB  - Dark respiration of foliage was measured in a 30-year-old stand of Abies amabilis
      in western Washington from June to November. Both laboratory and field
      measurements were used to study the effect of environmental and tree variables on
      respiration. Foliage respiration rates were most strongly influenced by needle
      temperature. After accounting for leaf temperature differences, foliage
      respiration decreased with depth in the canopy for all age classes of foliage.
      Respiration differences attributed to location within the canopy were greatest
      early in the growing season, but were still significant in November. Younger
      foliage respired more than older foliage in the upper canopy, but not in the
      lower canopy. Respiration differences due to foliage age were highly significant
      in the early growing season, but were not detectable by mid-October.

PMID- 14972845
TI  - Gas exchange during a soil drying cycle in seedlings of four black walnut
      (Juglans nigra L.) families.
AB  - Photosynthetic and stomatal responses to a soil drying cycle were examined in
      half-sib seedlings of four walnut (Juglans nigra L.) families. Well-watered
      seedlings of an Iowa seed source had significantly higher rates of net
      photosynthesis than seedlings from New York or Michigan sources. This superior
      photosynthetic potential was associated with both greater stomatal conductance
      and mesophyll capacity for CO(2) fixation. In a drying soil, net photosynthesis
      and leaf conductance to water vapor of all families declined substantially, even
      under mild water stress. These responses were more strongly related to soil water
      status, as estimated by predawn leaf water potential, than to leaf water
      potential at the time of gas exchange measurement. There were no differences
      among families in the pattern of gas exchange response to developing water
      stress; however, families differed in capacity for recovery of gas exchange from
      water stress following rehydration. Sensitivity of photosynthesis of black walnut
      seedlings to water stress may be associated with poor growth and survival of this
      species in xeric habitats.

PMID- 14972846
TI  - Cadmium uptake in Norway spruce (Picea abies (L.) Karst.) seedlings.
AB  - Root elongation of Norway spruce (Picea abies (L.) Karst.) seedlings was
      inhibited in the presence of 5 microM Cd, but was unaffected by a Cd
      concentration at 0.05 microM. Nutrient solutions labeled with (109)Cd were used
      to investigate the influence of pH, cations and the metabolic inhibitor 2,4
      dinitrophenol (DNP) on the uptake of Cd by roots of intact spruce seedlings.
      Extracellular Cd was removed by washing the roots, and the relative amounts of Cd
      in the root apoplast and symplast estimated. In the presence of DNP, Cd uptake
      was reduced at 0.05 microM (non-toxic) but not at 5 microM Cd (toxic). At 0.05
      microM Cd, the uptake of Cd into both the apoplast and symplast was dependent on
      the pH of the nutrient solution. Lower pH decreased Cd accumulation. Aluminum
      supplied at 100 or 500 microM lowered the Cd concentrations of both the apoplast
      and symplast. An increase in Ca or Mg supply reduced the Cd concentration of the
      apoplast but not of the symplast. In the presence of 5 microM Mn, the
      concentration of Cd in the symplast decreased by 44% compared to the control (1
      microM Mn). High concentrations of Zn or Hg did not affect the Cd concentration
      of the roots.

PMID- 14972847
TI  - In situ experimental freezing produces symptoms of winter injury in red spruce
      foliage.
AB  - Two mechanisms have been proposed to explain winter injury to needles of red
      spruce (Picea rubens Sarg.): (1) desiccation, which is characterized by net loss
      of foliar water from the needle to the environment, with cell injury resulting
      from dehydration; and (2) freezing, which is characterized by direct injury to
      cells resulting from intracellular or extracellular ice formation during exposure
      to low temperature. To compare the separate and combined effects of freezing and
      desiccation, branches of a mature red spruce at 1160 m were (a) experimentally
      frozen in situ to -50 degrees C; (b) cut and tied in their original orientation
      and allowed to desiccate passively; or (c) both frozen in situ and cut and tied
      in their original orientation. Needle water content, electrolyte leakage (an
      index of cell injury), and needle color were monitored for 60 days after
      treatment. Freezing resulted in immediate increases in electrolyte leakage, rapid
      water loss, and reddening necrosis of needles similar to that of naturally
      injured needles. Cutting resulted in more gradual water loss, no significant
      changes in electrolyte loss until severe desiccation had occurred, and a change
      in the color of the needles to a dull green. Because freezing produced reddening
      necrosis, a key symptom of winter injury, whereas desiccation did not, we
      conclude that freezing is probably the primary cause of winter injury in red
      spruce, and that desiccation is a secondary effect.

PMID- 14972848
TI  - Tree allometry, leaf size and adult tree size in old-growth forests of western
      Oregon.
AB  - Relationships between tree height and crown dimensions and trunk diameter were
      determined for shade-tolerant species of old-growth forests of western Oregon.
      The study included both understory and overstory species, deciduous and evergreen
      angiosperms and evergreen conifers. A comparison of adult understory species with
      sapling overstory species of similar height showed greater crown width and trunk
      diameter in the former, whether the comparison is made among conifers or
      deciduous trees. Conifer saplings had wider crowns than deciduous saplings, but
      the crown widths of the two groups converged with increase in tree height.
      Conifer saplings had thicker trunks than deciduous saplings of similar crown
      width, possibly because of selection for resistance to stem bending under snow
      loads. The results suggest that understory species have morphologies that
      increase light interception and persistence in the understory, whereas overstory
      species allocate their biomass for efficient height growth, thereby attaining the
      high-light environment of the canopy. The greater crown widths and the additional
      strength requirements imposed by snow loads on conifer saplings result in less
      height growth per biomass increment in conifer saplings than in deciduous
      saplings. However, the convergence in crown width of the two groups at heights
      greater than 20 m, and the proportionately smaller effect of snow loads on large
      trees, may result in older conifers equalling or surpassing deciduous trees in
      biomass allocation to height growth.

PMID- 14972849
TI  - Dynamics of swaying of Picea sitchensis.
AB  - Six 26-year-old Sitka spruce (Picea sitchensis (Bong.) Carr.) trees growing in a
      Scottish plantation were swayed manually to determine their mechanical dynamics.
      The natural frequency of sway of the intact trees (mean height 14.2 m and mean
      stem diameter 14.5 cm at 1.3 m) was on average 0.35 Hz. The variation of this
      frequency with tree size was found to be well described by engineering mechanics
      theory. In particular, shape parameters could be defined for both intact and
      branchless trees, which, along with stem size, density and elasticity, could
      predict the natural sway frequency using a simple formula. The damping of sway
      was found to consist of three components, (1) interference of branches with those
      of neighbors, (2) aerodynamic drag on foliage, and (3) damping in the stem. For
      the sample of six trees, which spanned the diameter range at the experimental
      site, the importance of these three components to overall damping was in the
      ratio 5/4/1 for the median sized tree. Interference between neighbors depended on
      the distance to neighbors, as well as on the sizes of the chosen tree and its
      neighbors. Aerodynamic damping was larger for larger trees and the energy lost to
      this force was similar in magnitude to that calculated to be lost using drag
      coefficients from published wind tunnel and other studies. The amount of damping
      from the stem was linearly related to stem diameter.

PMID- 14972850
TI  - Physiological responses of pear thrips-damaged sugar maples to light and water
      stress.
AB  - We assessed the effect of feeding damage by pear thrips, Taeniothrips
      inconsequens Uzel (Thysanoptera:Thripidae), on gas exchange and water relations
      of sugar maple (Acer saccharum Marsh.) seedlings. Compared to undamaged
      seedlings, feeding punctures in the leaf epidermis of thrips-damaged seedlings
      decreased water use efficiency, increased leaf conductance to water vapor, and
      decreased predawn water potential. Under conditions of high soil water and high
      light intensity, carbon dioxide exchange rate (CER) was greater for thrips
      damaged than undamaged seedlings because of greater CO(2) conductance through
      feeding punctures. Under conditions of low soil water, CER was lower for thrips
      damaged than undamaged seedlings as a result of water stress. Carbon dioxide
      exchange rate at low light and low soil water was limited by non-stomatal
      factors, but no difference in non-stomatal limitation to CER was detected between
      thrips-damaged and undamaged seedlings. Leaf tissue water relations differed
      between thrips-damaged and undamaged seedlings and under high and low soil water
      conditions. The results suggest that the reduction in leaf area of thrips-damaged
      seedlings can be partially compensated by elevated CER under conditions of high
      light intensity and high soil water. However, high gas exchange rates through
      feeding punctures predisposes thrips-damaged seedlings to water stress that can
      reduce CER under conditions of low soil water.

PMID- 14972851
TI  - Net CO(2) assimilation of cacao seedlings following dark chilling.
AB  - Overnight exposure of cacao (Theobroma cacao L.) seedlings to chilling
      temperatures between 4.7 and 15.8 degrees C reduced net CO(2) assimilation rate
      (A) and stomatal conductance to water vapor (g(s)), with temperatures below 10
      degrees C causing severe inhibition. Net CO(2) assimilation rates of chilled
      seedlings recovered to those of nonchilled plants within 7 days. No differences
      in daytime intercellular CO(2) concentration (c(i)) with overnight temperature
      were observed on the first day after the chilling treatment, which indicates that
      the reduction in photosynthesis was not caused by the reduction in stomatal
      conductance. However, c(i) of chilled plants was much less than that of
      nonchilled plants on the second day after treatment, which suggests that chilling
      caused a change in stomatal response to CO(2) concentration. Even 7 days after
      treatment, when A had recovered to control values, g(s) of chilled leaves was
      only approximately 70% that of controls. Chilling did not inhibit A through an
      effect on leaf water potential, which was higher in chilled plants than in
      unchilled plants.

PMID- 14972852
TI  - Temporal variations in cold sensitivity of root growth in cold-stored white
      spruce seedlings.
AB  - We examined effects of soil temperature on the number of roots produced by white
      spruce (Picea glauca (Moench.) Voss) seedlings during the first month of growth
      following 0-30 weeks of storage in darkness at -2 degrees C. After storage,
      seedlings were planted in pots and placed in a controlled-environment chamber
      with a constant air temperature of 11 degrees C and a 16-h photoperiod. Water
      baths were used to keep soil temperature at 3, 7 or 11 degrees C. The number of
      long roots (> 10 mm) produced was strongly dependent on soil temperature. At soil
      temperatures of 3 or 7 degrees C, the number of long roots produced was only 11
      to 30% that at 11 degrees C. Seedlings that had been stored for 14 weeks and then
      planted in soil at 11 degrees C produced the greatest number of long roots. For
      seedlings planted in soil at 11 degrees C, the number of long roots increased
      with time of storage up to 14-18 weeks and then declined progressively with
      length of storage. No increase in number of long roots with length of storage up
      to 18 weeks was evident in seedlings planted in soil at 3 or 7 degrees C. The
      maximum number of short roots (5-10 mm) was observed in seedlings that had been
      stored for 17 weeks and then planted in soil at 7 or 11 degrees C.

PMID- 14972853
TI  - Evaluating progress toward closed forest models based on fluxes of carbon, water
      and nutrients.
AB  - Closed system models are defined as mathematical models of systems having
      specified boundaries within which all flows into and out of the system are
      accounted for. Closure is obtained experimentally when we can measure all the
      flows and do not depend on residuals. The meeting on which this volume is based
      discussed a range of models and approaches to modeling, and the possibility of
      achieving closure. There was general agreement that we can develop closed system
      models of the water balance, carbon cycle and nutrient fluxes at the stand level.
      Confidence in our ability to account for all the flows is greatest for water,
      decreasing progressively for carbon and nutrients. The priority areas for
      research on the carbon balance are belowground processes, foliage dynamics and
      respiration. The problems requiring particular attention in relation to the water
      balance are the measurement of interception losses, lateral flow in the soil and
      evaporation from snow. Areas warranting particular research attention in relation
      to nutrient fluxes through forest stands are the rates, and the controls on
      rates, of nutrient uptake by trees, and rates of mineralization with emphasis on
      the importance of microbial processes at the ecosystem level. Most models are
      written for uniform conditions. Forests are not uniform so the problem of
      heterogeneity, and how to deal with it in models, requires considerable
      attention, as does the question of how to scale up, to deal with large areas.
      There are a great many forest models of all types and the continual development
      of new ones may not be an effective use of research resources. There is a need
      for some assessment of the range of models currently existing, or under
      development, and for moves toward a directed strategy of model structure and
      development.

PMID- 14972854
TI  - Modeling the water balance of a small Pinus radiata catchment.
AB  - An hourly biophysical model was used to calculate the water balance over a period
      of one year for an 8.7-ha catchment with a closed-canopy, 13-year-old Pinus
      radiata D. Don forest in the central North Island, New Zealand. Components of the
      model are transpiration from the dry tree canopy, evaporation from the partially
      wet tree canopy and stems, evaporation from the understory and soil, and drainage
      from a single-layer root zone. The model requires input of hourly weather data
      (net radiation, air and wet bulb temperatures, windspeed, and rainfall), tree
      stand characteristics (average height, tree number, leaf area index), physical
      characteristics of the site (root zone depth, relationship between root zone
      matric potential and volumetric water content, the relationship between the rate
      of drainage from the root zone and volumetric water content, and the area of open
      stream channels). A submodel of the response of stomatal conductance to air
      saturation deficit and root zone matric potential is also required. Tree
      transpiration (704 mm year(-1) or 50% of annual rainfall) was a dominant
      component of the catchment water balance. Estimated evaporation from the wet tree
      canopy was 203 mm year(-1) (15%). Evaporation from the understory was much less,
      amounting to 94 mm year(-1) (7%) and an increase in water storage for the 3.5 m
      root zone depth was estimated to be 53 mm year(-1) (4%). Estimated daily rates of
      drainage generally agreed well with measurements of streamflow, although
      estimated annual drainage (349 mm year(-1), 24%) exceeded measured streamflow
      (234 mm year(-1)). The significance of the results is discussed in relation to
      closure of the hydrologic balance.

PMID- 14972855
TI  - Models of water flux through forest stands: critical leaf and stand parameters.
AB  - The basis for estimating water flux through forest stands is described using
      models. By means of the Penman-Monteith equation, transpiration is described in
      relation to the degree of coupling between the canopy and the surrounding air.
      Models of canopy and aerodynamic conductance are available, but more mechanistic
      models of stomatal conductance, and further development of turbulence theory, are
      needed along with improved estimates of leaf area index, leaf area distribution,
      and seasonal dynamics. Three models are presented to show current capabilities in
      estimating water uptake and flux through tree components, including the effects
      of capacitance. Defining conductance to water movement through tree components in
      terms of the properties of the pathway (sapwood area, sapwood relative
      conductivity, leaf area) is a useful functional approach that can be tested for a
      range of species at different sites. Further research is required to relate water
      conducting properties of tree components to architectural arrangement, especially
      for roots, and improved methods for measuring water potentials and partial flows
      at different points within the system are necessary. The role of water potential
      and the significance of its variability within a canopy are discussed. Relating
      growth processes to an integral of water potential (an accumulated product of
      water potential and time) is recommended. The need for scaling and integrating
      information about processes from one level to higher levels is recognized. The
      importance of understanding the roles that temporal, spatial, and developmental
      levels have on the ability to scale or integrate individual leaf measurements of,
      for example, leaf conductance to the stand level is emphasized.

PMID- 14972856
TI  - Carbon gain and water use in pinyon pine-juniper woodlands of northern New
      Mexico: field versus phytotron chamber measurements.
AB  - We compared phytotron chamber- and field-obtained gas exchange parameters from a
      semiarid pinyon pine-juniper (Pinus edulis Engelm.-Juniperus monosperma (Engelm.)
      Sarg.) community in northern New Mexico, an ecosystem where carbon gain could be
      limited by both water and nitrogen availability. In both species, variations in
      rates of photosynthesis with xylem pressure potential (Psi) and minimum Psi for
      positive carbon gain were similar in the field and phytotron chamber studies.
      Rates of maximum photosynthesis were greater in pinyon pine than in juniper in
      both the field and phytotron chamber studies. Pinyon pine showed a greater
      response to increases in Psi than juniper, although juniper was able to continue
      photosynthetic activity at lower values of Psi than pinyon pine. There were
      significant differences in instantaneous water use efficiency (WUE) measured in
      the field and the phytotron chamber, although relative rankings of the species
      and their responses to Psi were similar. In the field experiments, WUE of N
      fertilized plants was marginally greater in pinyon pine than juniper during the
      wet season, and in both the field and phytotron chamber experiments instantaneous
      values of WUE were greater in juniper during dry seasons or during drying cycles.
      However, delta(13)C values suggested that pinyon pine had greater seasonally
      integrated values of WUE, perhaps because this species ceases stomatal activity
      during dry seasons. Field data showed significant interactions between N and WUE,
      as well as between Psi and the degree of response to N, however, there were
      insufficient data to derive predictive equations because of the limited range of
      environmental conditions encountered in the field.

PMID- 14972857
TI  - Carbon budgets of temperate forest ecosystems.
AB  - A summary of carbon-budget data from 30 forest stands is presented together with
      information on both above- and belowground ecosystem components. Only 10 of the
      stands had complete biomass data, 21 had complete productivity data and six had
      heterotrophic, or autotrophic respiration data, or both. The most comprehensive
      stand-level data have been collected for Pinus spp., Pseudotsuga menziesii, Abies
      amabilis and Liriodendron tulipifera. Only incomplete carbon budgets are
      available for most ecosystems studied, because measurements have been limited to
      one or several ecosystem processes (e.g., decay, productivity, storage). Based on
      the few complete C-budget studies that have been published, it is concluded that
      tree species differ in annual turnover of tissues.

PMID- 14972858
TI  - Relationship of forest productivity to nutrient and carbon supply-a modeling
      analysis.
AB  - A simple model of photosynthetic and nutritional controls over foliar dynamics is
      analyzed to compare the magnitude of the growth response of forest stands to
      increased rates of photosynthesis and nutrient supply. According to the model,
      productivity achieved at canopy closure is sensitive to nutrient supply, except
      where nutrient availability exceeds the plants' uptake capacity. Plants growing
      under nutrient-limited conditions can only respond positively to enhanced
      photosynthetic rates if they simultaneously increase their nutrient uptake, or
      reduce nutrient concentrations in stem, branch, root or senescing leaf tissue, or
      shift their carbon allocation in favor of biomass components with low nutrient
      concentrations. In particular, a response is more likely where considerable
      internal cycling of nitrogen occurs before leaf senescence, or where foliar
      allocation decreases with decreasing leaf nutrient concentration.

PMID- 14972859
TI  - A general biogeochemical model describing the responses of the C and N cycles in
      terrestrial ecosystems to changes in CO(2), climate, and N deposition.
AB  - A model that simulates carbon (C) and nitrogen (N) cycles in terrestrial
      ecosystems is developed. The model is based on the principle that the responses
      of terrestrial ecosystems to changes in CO(2), climate, and N deposition will
      encompass enzymatic responses, shifts in tissue stoichiometry, changes in biomass
      allocation among plant tissues, altered rates of soil organic matter turnover and
      N mineralization, and ultimately a redistribution of C and N between vegetation
      and soils. The model is a highly aggregated, process-based, biogeochemical model
      designed to examine changes in the fluxes and allocation of C and N among
      foliage, fine roots, stems, and soils in response to changes in atmospheric CO(2)
      concentration, temperature, soil water, irradiance, and inorganic nitrogen
      inputs. We use the model to explore how changes in CO(2) concentration,
      temperature, and N inputs affect carbon storage in two ecosystems: arctic tundra
      and temperate hardwood forest. The qualitative responses of the two ecosystems
      were similar. Quantitative differences are attributed to the initial distribution
      of C and N between vegetation and soils, to the amounts of woody tissue in the
      two ecosystems, and to their relative degree of N limitation. We conclude with a
      critical analysis of the model's strengths and weaknesses, and discuss possible
      future directions.

PMID- 14972860
TI  - Modeling changes in red spruce carbon balance and allocation in response to
      interacting ozone and nutrient stresses.
AB  - The simulation model TREGRO was developed to analyze the response of red spruce
      saplings to multiple stresses, such as drought, nutrient deficiency, and exposure
      to pollutants. The model provides a method of identifying changes in structural
      and non-structural carbon resources in the tree that may become measurable only
      after many years of exposure. The model is based on the assumption that the
      ability of plants to take up and use carbon, water, and nutrients depends on the
      interrelationships in availability among the three resources. Consequently, the
      model simulates the simultaneous cycling of these resources. In the model, the
      tree is divided into the following compartments: a canopy of leaves grouped by
      age class, branches, stem, and coarse and fine roots in a number of soil
      horizons. In each of these compartments we track three carbon pools: living
      structure, dead structure or wood, and total non-structural carbohydrate. The
      model calculates the photosynthesis of an entire red spruce tree each hour as a
      function of ambient environmental conditions and the availability of light,
      water, and nutrients; the daily redistribution of carbon throughout the plant;
      and the loss of carbon by respiration and senescence. To accomplish this task,
      the model tracks the flow of carbon dioxide to the sites of fixation within the
      leaves, the availability of light in the canopy, water and nutrient resources in
      each of three soil horizons, and the amounts of these resources taken up by the
      tree. Soil and plant water potentials, photosynthesis, and leaf respiration are
      simulated on an hourly timestep; nutrient uptake, allocation and growth are
      computed on a daily timestep. Through a set of example simulations, we
      demonstrate how the model can be used to examine the mechanisms by which plants
      respond to stresses experienced alone and in combination. The model was used to
      predict the growth decrease and the shifting pattern of carbon allocation
      expected for an isolated tree exposed to ozone and decreased nutrient
      availability due to acidic deposition. Decreased nutrient availability resulted
      in decreased growth and preferential carbon allocation to roots, which helped to
      alleviate the nutrient stress. Ozone stress also resulted in decreased plant
      growth but had the opposite effect on allocation patterns, with most of the
      growth reduction occurring in roots. The effect of simultaneous ozone and
      nutrient stress on tree growth was less than the sum of the independent single
      stresses, contrary to our expectation. This modeling approach can aid in
      evaluating the long-term effect of stress on resource availability, the potential
      for gradual deterioration of tree health under long periods of stress, and
      imbalances in growth accompanying shifts in carbon allocation caused by stress.

PMID- 14972861
TI  - FOREST-BGC, A general model of forest ecosystem processes for regional
      applications. II. Dynamic carbon allocation and nitrogen budgets.
AB  - A new version of the ecosystem process model FOREST-BGC is presented that uses
      stand water and nitrogen limitations to alter the leaf/root/stem carbon
      allocation fraction dynamically at each annual iteration. Water deficit is
      defined by integrating a daily soil water deficit fraction annually. Current
      nitrogen limitation is defined relative to a hypothetical optimum foliar N pool,
      computed as maximum leaf area index multiplied by maximum leaf nitrogen
      concentration. Decreasing availability of water or nitrogen, or both, reduces the
      leaf/root carbon partitioning ratio. Leaf and root N concentrations, and maximum
      leaf photosynthetic capacity are also redefined annually as functions of nitrogen
      availability. Test simulations for hypothetical coniferous forests were performed
      for Madison, WI and Missoula, MT, and showed simulated leaf area index ranging
      from 4.5 for a control stand at Missoula, to 11 for a fertilized stand at
      Madison, with Year 50 stem carbon biomasses of 31 and 128 Mg ha(-1),
      respectively. Total nitrogen incorporated into new tissue ranged from 34 kg ha(
      1) year(-1) for the unfertilized Missoula stand, to 109 kg ha(-1) year(-1) for
      the fertilized Madison stand. The model successfully showed dynamic annual carbon
      partitioning controlled by water and nitrogen limitations.

PMID- 14972862
TI  - Simulating the effects of climatic variation on stem carbon accumulation of a
      ponderosa pine stand: comparison with annual growth increment data.
AB  - Simulation models of ecosystem processes may be necessary to separate the long
      term effects of climate change on forest productivity from the effects of year-to
      year variations in climate. The objective of this study was to compare simulated
      annual stem growth with measured annual stem growth from 1930 to 1982 for a
      uniform stand of ponderosa pine (Pinus ponderosa Dougl.) in Montana, USA. The
      model, FOREST-BGC, was used to simulate growth assuming leaf area index (LAI) was
      either constant or increasing. The measured stem annual growth increased
      exponentially over time; the differences between the simulated and measured stem
      carbon accumulations were not large. Growth trends were removed from both the
      measured and simulated annual increments of stem carbon to enhance the year-to
      year variations in growth resulting from climate. The detrended increments from
      the increasing LAI simulation fit the detrended increments of the stand data over
      time with an R(2) of 0.47; the R(2) increased to 0.65 when the previous year's
      simulated detrended increment was included with the current year's simulated
      increment to account for autocorrelation. Stepwise multiple linear regression of
      the detrended increments of the stand data versus monthly meteorological
      variables had an R(2) of 0.37, and the R(2) increased to 0.47 when the previous
      year's meteorological data were included to account for autocorrelation. Thus,
      FOREST-BGC was more sensitive to the effects of year-to-year climate variation on
      annual stem growth than were multiple linear regression models.

PMID- 14972863
TI  - Application of a nutrient cycling model (NuCM) to a northern mixed hardwood and a
      southern coniferous forest.
AB  - The nutrient cycling model, NuCM, which incorporates state-of-the-art
      understanding of the biogeochemical and transport processes controlling nutrient
      cycles, simulates vegetation growth, litterfall and decay, soil biogeochemical
      processes, and movement of water. Output of the model includes the available
      nutrients in soil strata and vegetation pools and the fluxes between pools on a
      weekly, monthly or annual basis. Solution and adsorbed concentrations in the
      various soil layers can be plotted versus time. The model has been used to
      simulate effects of acidic deposition on nutrient status at two sites: Huntington
      Forest, New York and Smokies Tower, Tennessee. Model results show only minor
      changes in nutrient status at the sites over the next 65 years at current rates
      of acidic deposition. The results also show only small differences in soil
      nutrient status between two alternative scenarios for reduction of SO(x)
      emissions. Neither "threshold effects" nor abrupt changes in nutrient pool sizes
      occurred in either of the simulations.

PMID- 14972864
TI  - Nutrient retranslocation in temperate conifers.
AB  - Controversy exists about the relationship between retranslocation from leaves and
      uptake from soil in the mineral nutrition of trees. Evidence is presented to show
      that uncertainty has arisen partly because the significance of retranslocation
      from young leaves has been overlooked. Retranslocated nutrients are important for
      the production of new tissues at all stages of development from the seedling to
      the mature tree. Retranslocation is not, as has been thought, primarily
      associated with senescence and late stages in stand development. The key
      variables that determine the amount and rate of retranslocation in trees are the
      rates of nutrient uptake and growth. The amount and rate of retranslocation
      increase as tree growth rate increases, indicating that soil and environmental
      factors that promote growth also promote nutrient retranslocation.
      Retranslocation efficiency is increased by high soil fertility and rapid nutrient
      uptake and growth. Knowledge of the relationships between nutrient uptake and
      nutrient retranslocation should facilitate the development of simple models of
      whole-tree growth. Because nutrient retranslocation is driven by shoot growth
      rather than by nutrient supply in the soil, there is continual competition among
      shoots for internal nutrient reserves. This has implications for models
      describing shoot growth and crown development. Research on gas exchange processes
      in the crown should pay greater attention to the highly dynamic nature of
      nutrients in foliage.

PMID- 14972865
TI  - Considerations in modeling change in temperate forest nitrogen cycles.
AB  - The general features of nitrogen (N) cycles in temperate forests and the
      important processes to consider when modeling change in these cycles include
      atmospheric inputs, N fixation, litter (root and aboveground) transfers and
      decomposition, soil processes, N uptake and effects on productivity and litter
      quality, and N outputs. Nitrogen cycling is closely linked with the carbon (C)
      and water cycles. Thus models of N cycling must include aspects of these other
      cycles. Although much is known about individual processes, development of a
      generic model of forest N cycling is not possible at present because the links
      and interactions among the individual processes are not well understood. The
      weakest links with respect to the N cycle are: quantification of atmospheric
      (especially dry) deposition rates in polluted environments, controls on C and N
      allocation in vegetation, controls on N turnover in fine roots, controls on
      decomposition of the older components of soil organic matter, and feedbacks among
      N availability, litter "quality" and subsequent N mineralization rates. To
      examine possible effects of long-term change in climate or atmospheric chemistry
      on the storage of C and other elements in forest ecosystems, we need to model in
      detail the effects of these factors on complex soil processes such as organic
      matter decomposition. Some promising models have been developed, but they need to
      be validated across a range of forest types before they can be used with
      confidence for long-term prediction. Mean annual leaf litter N concentration
      offers potential as a simple index of annual N uptake in forests.

PMID- 14972866
TI  - Performance of a canopy light interception model for conifer shoots, trees and
      stands.
AB  - A hierarchical approach was used to evaluate the behavior of a canopy light
      interception model using submodels for interception at levels of the shoot, crown
      and stand. Mean silhouette areas of individual shoots of lodgepole pine (Pinus
      contorta var. latifolia Engelm.) calculated assuming spherical shoot orientation
      agreed well with silhouette areas measured with a video projection system. A
      theoretical mean silhouette to total leaf area ratio (STAR) calculated using
      measured shoot characteristics and a model of shoot geometry agreed reasonably
      well with STAR values from measured shoot silhouette and leaf areas, although the
      range of calculated STAR values was slightly lower than that of the measured
      values. The shadow areas of tree crowns were underestimated for lodgepole pine;
      however, a model using regular shoot dispersion in the crown gave better
      agreement than a model based on random shoot dispersion. The underestimates may
      have been caused by underestimation either of leaf or branch area for the crowns
      or of the extinction coefficient. Two equations used to calculate leaf area from
      sapwood area measurements both underestimated leaf area. Accordingly, there are
      too many uncertainties to determine whether crown interception is best
      represented by a random or regular distribution of shoots. Mean canopy
      transmission in the Engelmann spruce (Picea engelmannii Parry ex Engelm.) stand
      was estimated very well by a random (Poisson) model of the spatial distribution
      of trees, whereas, in the lodgepole pine stand, a regular (hexagonal) model gave
      the best results. The Engelmann spruce stand had less regular tree spacing than
      the lodgepole pine stand. Taken as a whole, the weakest submodel for calculating
      canopy interception was the model for individual crown transmission, which
      underestimated crown shadow areas. However, the problem may be in leaf area
      estimates rather than in model performance.

PMID- 14972867
TI  - Interrelation between shoot characteristics and solar irradiance in the crown of
      Pinus contorta ssp. latifolia.
AB  - In Pinus contorta Doug. ssp. latifolia (Engelm.), annual shoot length increment,
      annual foliage production per shoot, and the daily integral of photosynthetically
      active radiation (DPAR) at shoot tips increased with height in the crown, whereas
      leaf longevity decreased. There was a decrease in DPAR along the shoot from the
      tip to beyond the oldest leaves, and the value reached at the point just proximal
      to the oldest leaf cohort was the same for all shoots from all crown locations,
      regardless of the age of the oldest leaves. The results suggest that shoot
      elongation, leaf production and leaf retention are controlled by the light
      environment within the crown. Because high irradiance promotes leaf production
      and low irradiance promotes leaf shedding, foliage is not randomly distributed in
      the crown.

PMID- 14972868
TI  - A simple method for estimating gross carbon budgets for vegetation in forest
      ecosystems.
AB  - Gross carbon budgets for vegetation in forest ecosystems are difficult to
      construct because of problems in scaling flux measurements made on small samples
      over short periods of time and in determining belowground carbon allocation.
      Recently, empirical relationships have been developed to estimate total
      belowground carbon allocation from litterfall, and maintenance respiration from
      tissue nitrogen content. I outline a method for estimating gross carbon budgets
      using these empirical relationships together with data readily available from
      ecosystem studies (aboveground wood and canopy production, aboveground wood and
      canopy biomass, litterfall, and tissue nitrogen contents). Estimates generated
      with this method are compared with annual carbon fixation estimates from the
      Forest-BGC model for a lodgepole pine (Pinus contorta Dougl.) and a Pacific
      silver fir (Abies amabilis Dougl.) chronosequence.

PMID- 14972869
TI  - A source-sink framework for coupling water, carbon, and nutrient dynamics of
      vegetation.
AB  - Feedbacks between photosynthesis and growth and the influence on these
      relationships of environmental factors are reviewed. The evidence indicates a
      strong dependence of photosynthesis on photosynthate utilization. It also
      indicates that growth is more sensitive than photosynthesis to water and mineral
      nutrient stress. As a consequence, many relationships between photosynthesis and
      external driving variables are confounded by internal feedback effects that
      reflect the influence of external factors on growth. A source-sink framework for
      modeling carbon dynamics with coupled water and nutrient interactions in soil
      plant systems is outlined. Simulations based on these concepts suggest that sink
      feedback regulation of photosynthesis at various times in diurnal, wetting
      drying, and annual cycles is probably a common occurrence in soil-plant systems.

PMID- 14972870
TI  - Approaches to scaling up physiologically based soil-plant models in space and
      time.
AB  - Many broad-scale, environmental phenomena can be investigated by extrapolating
      from detailed study of events at a small scale. This paper evaluates approaches
      to the use of physiologically based soil-plant models for addressing broad-scale,
      environmental issues. When the space and time domains of a soil-plant simulator
      are extended, there is an increase in the variability of soil, plant, and weather
      variables, which can be dealt with by what is called extended-range modeling,
      ERM. There may also be a gain of phenomena not represented at the small scale,
      which can be dealt with by what is called phenomena-added modeling, PAM. As an
      example of ERM, a Monte Carlo procedure, called Latin hypercube sampling, is used
      to estimate annual photosynthate production of an oak-hickory forest under three
      atmospheric CO(2) concentrations. Phenomena-added modeling is illustrated by
      scaling up spatially from a vegetated plot to a watershed, and scaling up
      temporally from a physiological model with hourly time steps to a forest
      succession model operating on annual time steps. Where large-scale processes take
      place on a time scale similar to, or faster than, that of small-scale processes
      (plot-watershed case), less computation is required if the small-scale processes
      are built into the large-scale model and ERM is conducted with the expanded
      model. Phenomena-added modeling may be conducted by information transfer from a
      small-scale simulator to a large-scale simulator. This is also possible with
      Latin hypercube sampling by using the output frequency distributions from the
      small-scale model as input distributions for the large-scale model. The final
      outputs at the large scale are also frequency distributions, and these can be
      used to determine confidence intervals for statistical comparisons among modeling
      scenarios. The ERM and PAM methods are data and computer intensive; nevertheless,
      they can fill an important need for addressing large-scale issues that cannot be
      adequately addressed through other scaling up methods.

PMID- 14972871
TI  - Use of individual-based forest succession models to link physiological whole-tree
      models to landscape-scale ecosystem models.
AB  - Models of the spatial and temporal dynamics of forests that are based on
      competition between individual plants can be used to predict changes in the
      abundance of different tree species that result from natural succession or
      environmental change. These individual-based models can be designed to take into
      account important physiological and chemical properties of individual species,
      and thus provide a mechanism for scaling up the predictions of whole-plant
      physiological process models to intermediate-scale patterns in ecosystems and
      landscapes. Because plant species differ greatly in such properties as carbon
      fixation and evapotranspiration rates, models that predict species composition
      could provide information on the distribution of parameter values used as input
      for large-scale (e.g., "big leaf") models of regional vegetation-atmosphere
      interactions.

PMID- 14972872
TI  - The concept of closure in calculating carbon balance of forests: accounting for
      differences in spatial and temporal scales of component processes.
AB  - The concept of closure, which has been used extensively to calculate the heat and
      water budgets of forests, has led to advances in the understanding of how heat
      and water balances are controlled. The successful construction of closed heat and
      water budgets of forests can be attributed to the large scale of input and output
      fluxes relative to changes in storage, the comparative ease with which such
      fluxes can be measured, and the regularity with which forests cycle through
      discharge and recharge on diurnal and annual cycles. The applicability of simple,
      closed budget analysis for carbon balance of forests is less certain because
      changes in internal storage, which are of major significance, occur at different
      time scales for growth and decomposition. We conclude that carbon balance might
      best be modeled as an open system. For long-term predictions, the most important
      processes to consider are acclimation and adaptation, which occur at different
      spatial and temporal scales. Construction of a modeling procedure to accommodate
      this variation is discussed.

PMID- 14972873
TI  - Root respiration in Chamaecyparis obtusa trees.
AB  - We examined the respiration rate of root segments, which had a constant length in
      relation to their diameter, from three small and two large 26-year-old
      Chamaecyparis obtusa (Siebold & Zucc.) Endl. trees. The dependence of respiration
      rate on segment diameter was described by a power function with an exponent of
      about 1.5, except for the smallest sample tree, for which the exponent was 1.74.
      Unlike stem segments, root segments of similar diameter showed similar rates of
      respiration regardless of the tree from which the root segments had been taken.
      On the basis of the power function, we propose a new equation to estimate the
      total root respiration rate of a tree. The relationship between root respiration
      rate per tree and root weight can be expressed by a power function with an
      exponent of 1.11. The ratio of the specific respiration rate of stems to that of
      roots was 0.7 for the three smaller trees, and 1.1 to 1.3 for the two larger
      trees. In November, the stand respiration rate of roots was estimated to be 0.36
      kg CO(2) ha(-1) h(-1) for a root biomass (dry weight) of 28 Mg ha(-1).

PMID- 14972874
TI  - Differential adsorption of Al, Ca, and Mg by roots of red spruce (Picea rubens
      Sarg.).
AB  - The surface adsorption characteristics of red spruce (Picea rubens) roots were
      examined as a function of changes in external acidity and cation concentrations.
      Root cation exchange capacity varied significantly with changes in pH, increasing
      from 110 micromol(c) g(-1) at pH 3.5 to 155 micromol(c) g(-1) at pH 4.5, and
      reaching 250 micromol(c) g(-1) at pH 7.0. In general, Al adsorption by spruce
      roots was much greater than either Ca or Mg adsorption under the same initial
      conditions. However, root affinity for the divalent cations was proportionately
      much more sensitive to pH changes than was root affinity for Al. The fractions of
      adsorbed Ca and Mg increased by 50 to 100% as pH increased from 3.5 to 4.5,
      whereas the fraction of adsorbed Al remained relatively constant at both initial
      pH conditions. Competition experiments at pH 3.5 and 4.5 indicated that Al
      adsorption was strongly favored over Ca adsorption, except at low Al
      concentrations (~10 micromol l(-1)), high solution Ca(2+)/Al(3+) ion activity
      ratios (> 1.5 to 5.0), and at the higher pH. These results suggest that cell wall
      exchange sites in red spruce roots will tend to become progressively saturated
      with Al under the prevailing conditions of many acidic forest soils. To the
      extent that root adsorbed Al interferes with the active uptake of Ca and Mg, this
      process of competitive cation adsorption can contribute to impaired mineral
      nutrition in the spruce forest community.

PMID- 14972875
TI  - Analytical model of carbon storage in the trees, soils, and wood products of
      managed forests.
AB  - The carbon balance between managed forests and the atmosphere depends critically
      on the frequency and intensity of harvesting, and the lifetime of harvested
      products. To assess more quantitatively the nature of this dependence, a
      theoretical analysis, previously applied to carbon storage in trees and wood
      products only, is extended here to include the carbon in forest floor detritus
      and soil. A dimensionless combination of the parameters of the model, alpha, with
      critical value alpha(c), is identified such that for alpha < alpha(c), the
      conversion of old-growth forest to managed forest releases carbon to the
      atmosphere in the long term. Parameter alpha is given by the combination
      f(t)D/T(*), where f(t) is the fraction of old-growth forest carbon stored in
      trees, D is the residence time of harvested biomass (wood products and slash
      debris) within the system, and T(*) is the rotation period for maximum sustained
      yield (maximum mean annual increment). The critical value alpha(c), typically in
      the range 0.5-0.7, is derived for a variety of forest types. Parameter alpha
      determines the degree to which the carbon accumulated in harvested biomass
      offsets the loss of carbon in trees due to felling and in soils due to reduced
      litter input. When alpha > alpha(c), long-term carbon storage is optimized by
      harvesting for maximum sustained yield.

PMID- 14972876
TI  - Distribution of (14)C-labeled photosynthate in loblolly pine (Pinus taeda)
      seedlings as affected by season and time after exposure.
AB  - Distribution of (14)C-labeled photosynthate was determined in field-grown
      loblolly pine (Pinus taeda L.) seedlings on August 9 and October 15, 1984 and
      January 15 and March 12, 1985. Leaves on a lateral branch fixed (14)C
      photosynthetically and amounts of (14)C in seven biochemical fractions in each of
      six plant parts were determined 8, 24, and 72 h later. In all treatments, (14)C
      uptake was approximately 96% of that originally presented. Respiratory loss of
      (14)C ranged from 22 to 87% of uptake and increased sharply with increasing time
      after exposure and as the seedlings grew larger later in the study. Most (14)C
      was found in exposed leaves and very little occurred above the exposed branch.
      Amounts of (14)C decreased in the exposed leaves and increased in the roots with
      time after exposure and date. Sugars were generally the most heavily labeled
      fraction. Labeled sugar content of exposed leaves decreased by more than half
      between 8 and 72 h as sugars were metabolized and translocated to other parts,
      primarily the roots. In roots, the labeling of starch and residue (structural
      compounds) increased greatly with transport time and season. In all plant parts,
      proteins and amino acids contained very little (14)C regardless of date or time.

PMID- 14972877
TI  - Seasonal variation in ethylene concentration in the wood of Pinus sylvestris L.
AB  - Ethylene concentrations were determined in gas samples extracted from sealed
      holes made in the sapwood and heartwood of stems of 70-100-year-old Scots pine
      (Pinus sylvestris L). Gas could be collected from the heartwood holes by lowering
      the pressure by means of a large syringe. However, attempts to extract gas from
      air spaces in the sapwood with the same technique failed, presumably because of
      lack of an interconnected system of gas-filled canals. High ethylene
      concentrations, usually in excess of 1 ppm, accumulated in the sapwood holes
      within one day after sealing. Ethylene concentrations in the sapwood rose to 3-7
      ppm during the growing season, and decreased to 0.1-0.3 ppm during the winter. In
      response to extreme drought, sapwood ethylene concentration increased to 30 ppm,
      followed by a rapid decrease after the onset of rain. Ethylene concentrations in
      gas samples from the heartwood were consistently lower than 1 ppm. The lowest
      values, about 0.1 ppm, were found during the autumn and early winter, whereas
      values around 0.5 ppm were typical from February to August.

PMID- 14972878
TI  - The utilization of old phenological time series of budburst to compare models
      describing annual cycles of plants.
AB  - A phenological time series of the date of budburst of birch (Betula pendula) was
      constructed using data from the years 1907-1950. Data for the years 1908, 1910
      1915 and 1930 are missing. The phenological observations were made at Saarijarvi
      (62 degrees 42' N, 25 degrees 44' E) in Central Finland. Different models
      describing the rate of development in the spring were analyzed using temperature
      data from the city of Jyvaskyla about 60 km to the southeast of Saarijarvi. The
      models based on temperature sum gave more accurate predictions of the date of
      budburst than the model based on time. Differences between different development
      rates seemed to be negligible when computing the temperature sum.

PMID- 14972879
TI  - New root growth of Douglas-fir seedlings at low carbon dioxide concentration.
AB  - New root growth of conifer nursery seedlings is dependent on light, but whether
      this is necessary only for photosynthesis, or also has some other root growth
      promoting effect is unknown. This question was investigated using one-year-old
      Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) seedlings grown at two
      nurseries from the same seed lot and taken from cold storage in March and April.
      New root production was examined in two 10-day root growth capacity (RGC)
      experiments. Seedlings were subjected to one of four treatments: (1) control, (2)
      exclusion of light, (3) low CO(2) concentration, and (4) girdling to separate the
      phloem connection between shoot and root. Shoots were enclosed in Plexiglas
      cuvettes and supplied with scrubbed air to reduce the CO(2) concentration to 11
      to 22 microl l(-1) in the light. The closed system used in Experiment 1 was
      opened to the atmosphere briefly each day to restore O(2) to ambient, but this
      was unnecessary for the open system used in Experiment 2. In Experiment 1, new
      root production was affected by treatments in the order: control > low CO(2)
      concentration > dark > girdling. Greater new root production in the low CO(2)
      treatment compared with the dark treatment was attributed to brief increases in
      CO(2) to ambient concentrations when O(2) was restored each day. In Experiment 2,
      new root production at the low CO(2) concentration in the light was essentially
      the same as in darkness, but only 17% of the control value. Thus light appeared
      to play no part in new root production other than permitting photosynthesis.
      Limited production of new roots occurred in the absence of photosynthesis, which
      was further reduced by girdling, presumably because, after girdling, only root
      system reserves could be used.

PMID- 14972880
TI  - Clonal variation of Populus tremuloides responses to diurnal drought stress.
AB  - We have developed an automated microprocessor controlled system for subjecting
      hydroponically grown plants to drought. Pumps and valves were used to move
      nutrient solutions into and out of a system of culture vessels in a growth
      chamber to provide periods of drought. Drought conditions were obtained by
      exposing the roots of hydroponically grown clones of aspen, Populus tremuloides
      Michx., to air in culture vessels temporarily emptied of nutrient medium. Over a
      3-week period, the daily duration of drought was increased from 0 to 6 h. During
      this period, the plants became increasingly tolerant to drought, as shown by a
      decreasing propensity to wilt. All three clones sustained diurnal drought periods
      of 6 h for up to 5 weeks without detectable deterioration of health. Typical
      drought stress symptoms were observed including inhibition of growth, increased
      tissue amino acid content, and decreased water, solute, and turgor potentials in
      young leaves. In all clones, control plants had leaf water potentials between 
      1.0 and -1.6 MPa, whereas leaf water potentials of drought-treated plants were
      significantly lower, ranging from -1.7 to -3.0 MPa. Only one of the clones showed
      a significant decrease in leaf solute potential in response to drought. The
      decrease in leaf solute potential paralleled the decrease in water potential
      resulting in no significant difference in turgor potential. The other two clones
      had nonsignificant decreases to more negative leaf solute potentials under
      drought conditions resulting in significantly lowered turgor potentials. Leaf
      water potentials, solute potentials, and turgor potentials of the drought-treated
      plants returned to control values within two hours after rewatering. The growth
      inhibitions observed could not have been the consequence of loss of turgor. These
      results demonstrate genetic differences among aspen clones in water relations
      responses to drought.

PMID- 14972881
TI  - A device for studying the influence of declining water table on poplar growth and
      survival.
AB  - Riparian poplar forests are declining downstream from many dams in the western
      prairie regions of North America. Drought-induced seedling and sapling mortality
      caused by abrupt drops in water table level following river flow regulation may
      be contributing to this forest decline. Here we describe a device, the rhizopod,
      for studying the influence of a changing water table on poplar seedling survival
      and growth. Seeds of a natural poplar hybrid (Populus deltoides x P. balsamifera)
      were planted in five rhizopods and treated to water table declines of 0, 1, 2, 4,
      or 8 cm day(-1). Each rhizopod consisted of 15 growth tubes connected to a
      central water reservoir through which the water level was regulated. Seedling
      survival was over 90% in rhizopods in which water table declined by 0, 1 or 2 cm
      day(-1), but was reduced to about 40% and less than 25% in rhizopods in which the
      water table level declined by 4 and 8 cm day(-1), respectively. Maximum shoot
      height, leaf number, and leaf area were observed in the rhizopod with a constant
      water table and decreased progressively with increasing rates of water table
      decline. Maximum root mass and length were observed in plants subjected to
      declines in water table level of 0 and 1 cm day(-1), respectively.

PMID- 14972882
TI  - Fall lifting and long-term freezer storage of ponderosa pine seedlings: effects
      on post-storage leaf water potential, stomatal conductance, and root growth
      potential.
AB  - Post-storage water relations, stomatal conductance, and root growth potential
      were examined in ponderosa pine (Pinus ponderosa Dougl. ex Laws.) seedlings from
      high- and low-elevation seed sources that had been lifted either in October or
      November and freezer stored, or in March, and then grown hydroponically in a
      greenhouse for 31 days. Seedlings lifted in October had poor root initiation (<
      17 new roots per seedling), low predawn leaf water potentials (< -1.5 MPa), and
      low stomatal conductance (7.10 mmol m(-2) s(-1)) compared with seedlings lifted
      in November or March. There was little difference in post-storage water relations
      and stomatal conductance between seedlings lifted in November and those lifted in
      March. Throughout the 31-day test, seedlings from the high-elevation seed source
      produced 3-9 times more new roots, had higher predawn leaf water potentials (-0.6
      to -0.7 MPa versus -1.1 to -1.6 MPa), and 1.3-5 times greater stomatal
      conductance than seedlings from the low-elevation seed source. For all seedlings
      on Day 31, the number of new roots was significantly related to predawn leaf
      water potential (r(2) = 0.65) and stomatal conductance (r(2) = 0.82). Similarly,
      the dry weight of new roots per seedling on Day 31 accounted for a significant
      amount of the variation in predawn leaf water potential (r(2) = 0.81) and
      stomatal conductance (r(2) = 0.49).

PMID- 14972883
TI  - Quantification of two-year-old hybrid poplar root systems: morphology, biomass,
      and (14)C distribution.
AB  - Root morphology, biomass, and (14)C distribution were studied in two 2-year-old
      Populus trichocarpa x P. deltoides hybrids, which originated from hardwood
      cuttings, to determine the pattern of root distribution in a plantation and to
      refine methods for root recovery. The trees were labeled with (14)CO(2) and
      harvested after a 72-hour chase period. Roots attached to each labeled tree were
      analyzed for morphological traits at the time of harvest. Detached roots from
      within a 1-m(3) volume of soil surrounding each tree were separated from the soil
      and sorted on the basis of rooting depth and root diameter. Lateral roots > 2 mm
      in diameter had a largely horizontal orientation at their point of origin from
      the cutting and extended horizontally up to 4 m from the cutting. This resulted
      in considerable overlap of root systems in the plantation. Results from (14)C
      labeling indicated that 24 +/- 4% (+/- SD) of the carbon exported from branches
      labeled within two weeks after branch budset-was translocated to the root system.
      Dilution of the root (14)C label indicated that from 0 (> 5 mm diameter roots) to
      75% (< 2 mm diameter roots) of the roots recovered from within the 1-m(3) volume
      of soil surrounding a harvested tree originated from other trees. Total root
      biomass was 6 +/- 1 Mg ha(-1) for both hybrids. Sixty percent of the root biomass
      was recovered directly from excavation, 16% from coarse-sieving excavated soil,
      and 24% from re-sorting sieved soil. The study indicated that root growth of
      hybrid poplars may be rapid and extensive and that detailed sorting of soil
      subsamples substantially improves the recovery of fine roots < 2 mm in diameter.

PMID- 14972884
TI  - Importance of the method of leaf area measurement to the interpretation of gas
      exchange of complex shoots.
AB  - Net CO(2) uptake in full sunlight, total leaf area (TLA), projected leaf area of
      detached leaves (PLA), and the silhouette area of attached leaves in their
      natural orientation to the sun at midday on June 1 (SLA) were measured for sun
      shoots of six conifer species. Among species, TLA/SLA ranged between 5.2 and 10.0
      (x bar = 7.3), TLA/PLA ranged between 2.5 and 2.9 (x bar = 2.7) and PLA/SLA
      ranged between 2.0 and 3.7 (x bar = 2.2). These ratios were reflected in the
      ratios of net photosynthesis computed on the basis of the three measures of leaf
      area. The much smaller values for TLA/PLA compared with the values for TLA/SLA
      indicate that leaf orientation effects, or shading, or both, caused more
      variation in the interception of solar radiation than did variation in leaf
      geometry (i.e., cross-section). Silhouette leaf area of lodgepole pine, (Pinus
      contorta spp. latifolia) and subalpine fir (Abies lasiocarpa) shoots measured at
      the summer solstice varied almost 2-fold with diurnal changes in solar altitude
      and azimuth. Sun shoots of both species and shade shoots of lodgepole pine had
      the greatest SLA during the early morning and late afternoon. The midday decline
      in SLA was related to the relatively upright orientation of needles of subalpine
      fir sun shoots and the relatively upright orientation of both sun and shade
      shoots of lodgepole pine. Shade shoots of subalpine fir reached a maximum in SLA
      at midday and this was related to the near horizontal orientation both of the
      shoots and the needles on them.

PMID- 14972885
TI  - Canopy development in young sugi (Cryptomeria japonica) stands in relation to
      changes with age in crown morphology and structure.
AB  - In young sugi (Cryptomeria japonica D. Don) stands, crown shape (crown
      length/crown diameter) ratio, average branch inclination, and spatial density of
      foliage in the crown increased with stand age. Within crowns, foliage
      distribution increased from the apex downward and, until crown closure, reached a
      maximum near the crown base. After crown closure, the maximum occurred near the
      middle of the crown. In each stand, foliage distribution in the canopy showed
      almost the same vertical change over time as it did in individual crowns. The
      vertical distribution of foliage in the canopy moved upward with stand age,
      accompanied by an increase in canopy depth and leaf mass. The shape of the
      vertical distribution was almost symmetrical between the upper and lower halves
      in the closed stands, although slightly skewed downward. The logarithm of average
      spatial density decreased linearly as cumulative leaf mass increased with
      distance from the top of the canopy. The total cross-sectional area of the crowns
      exceeded the stand area from the middle of the canopy downward in the closed
      stands because of crown overlap. However, partly because of changes in crown
      morphology and structure, the increase in leaf mass with stand age did not always
      cause more severe crown competition.

PMID- 14972886
TI  - Gas exchange characteristics of Populus trichocarpa, Populus deltoides and
      Populus trichocarpa x P. deltoides clones.
AB  - Responses of net photosynthesis, dark respiration, photorespiration,
      transpiration, and stomatal conductance to irradiance, temperature, leaf-to-air
      vapor density difference (VDD), and plant water stress were examined in two
      Populus trichocarpa clones (one from a moist, coastal climate in western
      Washington and one from a dry, continental climate in eastern Washington), one P.
      deltoides clone, and two P. trichocarpa x P. deltoides clones. Light saturation
      of photosynthesis in greenhouse-grown trees occurred at about 800 micromol m(-2)
      s(-1) for P. deltoides, P. trichocarpa x P. deltoides, and the eastern Washington
      ecotype of P. trichocarpa, but at about 600 micromol m(-2) s(-1) for the western
      Washington ecotype of P. trichocarpa. Average net photosynthesis (at saturating
      irradiance and the optimum temperature of 25 degrees C) was 20.7, 18.8, 18.2 and
      13.4 micromol CO(2) m(-2) s(-1) for P. deltoides, P. trichocarpa x P. deltoides,
      and the eastern and western Washington clones of P. trichocarpa, respectively. In
      all clones, net photosynthesis decreased about 14% as VDD increased from 3 to 18
      g H(2)O m(-3). Stomatal conductance decreased sharply with decreasing xylem
      pressure potential (XPP) in all clones except the western Washington clone of P.
      trichocarpa. Stomata in this clone were insensitive to changes in XPP and did not
      control water loss. Complete stomatal closure (stomatal conductance < 0.05 cm s(
      1)) occurred at about -2.0 MPa in the eastern Washington clone of P. trichocarpa
      and around -1.25 MPa in the P. deltoides and P. trichocarpa x P. deltoides
      clones. Transpiration rates were highest in the P. trichocarpa x P. deltoides
      clone and lowest in the western Washington clone of P. trichocarpa. The P.
      deltoides clone and eastern Washington clone of P. trichocarpa had the highest
      water use efficiency (WUE) and the western Washington clone of P. trichocarpa had
      the lowest WUE. The hybrids were intermediate. It was concluded that: (1) gas
      exchange characteristics of eastern and western Washington clones of P.
      trichocarpa reflected adaptation to their native environment; (2) crossing the
      western Washington clone of P. trichocarpa with the more drought resistant P.
      deltoides clone produced plants better adapted to the interior Pacific Northwest
      climate, although the stomatal response to soil water deficits in the hybrid was
      conservative compared with that of the eastern Washington clone of P.
      trichocarpa; and (3) introducing eastern Washington clones of black cottonwood
      into breeding programs is likely to yield lines with favorable growth
      characteristics combined with enhanced WUE and adaptation to soil water deficits.

PMID- 14972887
TI  - Carbon dioxide enrichment accelerates the decline in nutrient status and relative
      growth rate of Populus tremuloides Michx. seedlings.
AB  - Changes in growth dynamics and mineral nutrient concentrations were measured in
      Populus tremuloides Michx., trembling aspen, grown for 100 days following
      germination in atmospheres containing 350 or 750 microl l(-1) CO(2). Seedlings
      were fertilized with nitrogen (N) at concentrations of 15.5 mM (high-N), 1.55 mM
      (medium-N), or 0.155 mM (low-N). Initially, relative growth rates were enhanced
      by CO(2) enrichment in each N regime, but the effects did not persist. In plants
      grown in high-N or medium-N, foliar concentrations of Ca and Mg decreased in
      response to CO(2) enrichment. During the 100-day study, whole-plant
      concentrations of N and P decreased in all treatments. The decreases in mineral
      nutrient concentrations over time were accelerated in CO(2)-enriched plants and
      accompanied the disappearance of the CO(2)-induced growth enhancement. It is
      concluded that the depression of relative growth rates often associated with long
      term CO(2) enrichment of plants may result from decreases in plant nutrient
      status.

PMID- 14972888
TI  - Influence of drought stress and low irradiance on plant water relations and
      structural constituents in needles of Pinus ponderosa seedlings.
AB  - The influence of low light on tolerance to prolonged drought was tested on
      unshaded and shaded seedlings of ponderosa pine (Pinus ponderosa var. scopulorum
      Dougl. ex Laws.). Unshaded seedlings of P. ponderosa var. ponderosa were also
      drought stressed to compare varietal responses to drought. The maximum irradiance
      received by shaded seedlings was 10% of full light. Seedlings were progressively
      drought stressed until predawn water potentials (Psi(x)) were -5.0 MPa. Relative
      water content (RWC) and the reciprocal of Psi(x) were analyzed by means of an
      unusual application of the pressure-volume relationship for determination of RWC
      of the apoplast (RWC(a)), osmotic potential at full turgor (Psi(oft)), and ratio
      of fully turgid weight to dry weight. Major varietal differences in drought
      response were in RWC(a) and needle cellulose content. The shaded seedlings showed
      tissue damage at relative water contents < 60%, and were killed by water deficits
      from which unshaded seedlings recovered. Correspondingly, shaded plants had
      significantly higher cell volume/cell mass ratio, Psi(oft), less cellulose in
      needle tissue, and lower RWC(a) than unshaded plants. These differences suggest
      that low irradiance restricts drought adaptation in ponderosa pine.

PMID- 14972889
TI  - Family variation in gas exchange, growth and leaf traits of black locust half-sib
      families.
AB  - Variations in several growth, gas exchange and leaf traits among greenhouse-grown
      black locust (Robinia pseudoacacia L.) seedlings from 11 half-sib families were
      investigated. Three weeks after germination, early growth rates ranged from a
      minimum of 1 cm d(-1) in the slowest growing family, to a maximum of 3 cm d(-1)
      in the fastest growing family. Significant family variation in net photosynthetic
      rate per unit leaf area (P(N)), stomatal conductance, chlorophyll content,
      height, diameter, stem dry weight and total dry weight was observed. Net
      photosynthetic rate declined with seedling age. Net photosynthetic rate per unit
      leaf area was significantly correlated (r < 0.4) with specific leaf area, total
      chlorophyll, root dry weight, foliage dry weight and total dry weight. The
      correlation coefficients were higher (r >/= 0.55) between P(N) x total leaf area
      and growth traits (height, stem dry weight, foliage dry weight and total dry
      weight). The study indicated that variation in leaf area among the families was
      one reason for the lack of a strong relationship between P(N) and growth.

PMID- 14972890
TI  - Consequences of rhizosphere acidification on delivery and uptake kinetics of soil
      phosphorus.
AB  - Experiments were undertaken to quantify the mechanisms by which acidity might
      affect phosphorus movement and uptake by black locust (Robinia pseudoacacia L.).
      Phosphorus diffusion rates in six forest soils were determined by desorption
      isotherm buffer power assays. Changes in diffusion as a function of acidity were
      measured using pH-adjusted desorption solutions. Depending on soil type and
      phosphorus source solubility, up to a fivefold increase in phosphorus diffusion
      rate was observed with an increased acidity of one pH unit. Phosphorus uptake
      rates of mycorrhizal and non-mycorrhizal black locust at pH 4 and pH 7 were
      determined from (32)P-labeled nutrient-depletion experiments. In mycorrhizal
      plants, the rate of phosphorus uptake at pH 4.0 was twice that observed at pH
      7.0. Non-mycorrhizal plant uptake rates were similar at both pH 4.0 and pH 7.0.
      The contribution of soil nutrient supply mechanisms to plant nutrient content
      increased with rhizosphere acidification. Uptake kinetics were also affected by
      rhizosphere acidification, but to a lesser extent.

PMID- 14972891
TI  - Net photosynthesis and leaf conductance of loblolly pine seedlings in 2 and 21%
      oxygen as influenced by irradiance, temperature and provenance.
AB  - Carbon dioxide assimilation and transpiration by secondary needles of two-year
      old loblolly pines (Pinus taeda L.) were measured at 2 and 21% (ambient) oxygen.
      Measurements were made with a Georgia provenance at irradiances (photosynthetic
      photon flux density) of 150, 300, 700 and 1200 micromol m(-2) s(-1) and a
      constant temperature of 25 degrees C, and at temperatures of 15, 25 and 35
      degrees C and a constant irradiance of 1200 micromol m(-2) s(-1). Measurements
      were made with provenances from North Carolina, Florida, Arkansas, and Georgia at
      25 degrees C and an irradiance of 1200 micromol m(-2) s(-1). There was no
      significant interaction between the effects of irradiance and oxygen on either
      net photosynthesis or leaf conductance. Taking all irradiances together,
      photosynthesis was 16% less and leaf conductance 28% less in 2% oxygen than in
      21% oxygen. There was a significant interaction between the effects of
      temperature and oxygen concentration on both net assimilation and leaf
      conductance. Net photosynthesis at 21% oxygen relative to that at 2% was
      significantly reduced at 25 and 35 degrees C, but not at 15 degrees C, whereas
      leaf conductance at 21% oxygen relative to that at 2% was significantly increased
      at 15 and 25 degrees C, but not at 35 degrees C. In the provenance study, net
      photosynthesis was 11% higher and leaf conductance 36% lower in 2% oxygen than in
      21% oxygen. There was no significant interaction between the effects of
      provenance and oxygen on either net photosynthesis or leaf conductance.

PMID- 14972892
TI  - Response of gas exchange to water stress in seedlings of woody angiosperms.
AB  - Responses of net photosynthesis (A), leaf conductance to water vapor (g(wv)) and
      instantaneous water use efficiency (WUE) to decreasing leaf and soil water
      potentials (Psi(l), Psi(s)) were studied in three-month-old white oak (Quercus
      alba L.), post oak (Q. stellata Wangenh.), sugar maple (Acer saccharum Marsh.),
      and black walnut (Juglans nigra L.) seedlings. Quercus seedlings had the highest
      A and g(wv) when plants were well watered. As the soil was allowed to dry, both A
      and g(wv) decreased; however, trace amounts of A were observed at a Psi(l) as low
      as -2.9 MPa in Q. stellata and -2.6 MPa in Q. alba and A. saccharum.
      Photosynthesis was not measurable at Psi(l) lower than -2.2 MPa in J. nigra and
      water stress-induced leaflet senescence was observed in this species. Within each
      species, g(wv) showed a similar relationship to soil and leaf Psi, but the
      response to Psi(l) was shifted to more negative values by 1.2 to 1.6 MPa. As
      Psi(s) declined below -1 MPa, the difference between soil and leaf Psi diminished
      because of the suppression of transpiration. There was no indication that Psi(s)
      had a more direct influence on g(wv) than did Psi(l). Water use efficiency showed
      an initial increase as the soil dried, followed by a decline under severe water
      stress. Water use efficiency was highest in J. nigra, intermediate in Quercus
      species and lowest in A. saccharum. There was an evident relationship between gas
      exchange characteristics and natural distribution in these species, with the more
      xeric species showing higher A and g(wv) under both well-watered and water
      stressed conditions. There was no trend toward increased efficiency of water use
      in the more xeric species.

PMID- 14972893
TI  - Seasonal changes in shoot water relations of Picea rubens at two high elevation
      sites in the Smoky Mountains.
AB  - Seasonal changes in water relations of current-year shoots of red spruce (Picea
      rubens Sarg.) were examined in relation to climatic conditions in trees growing
      at elevations of 1720 and 1935 m on Clingman's Dome, Tennessee, USA, where
      increment core data have shown that red spruce decline increases with elevation.
      Relative height growth of trees at 1720 m was 68% greater than in trees at 1935
      m. Following two weeks in July with only traces of precipitation, trees at both
      sites showed decreased saturated osmotic potentials. The magnitude of the
      reduction was greater in trees at the high elevation site than in trees at the
      low elevation site. However, during August and September, shoot water relations
      of trees at both sites were similar. Precipitation patterns and water relations
      measurements suggested that, at both sites, trees experienced water stress only
      briefly during the growing season and to a degree that could not account for the
      lower growth rates of trees at the high elevation site. During the period of cold
      hardening in October and November, trees at the low elevation site exhibited
      saturated osmotic potentials that were lower by 0.2 MPa and solute accumulation
      (osmol kg(dw) (-1)) that was 48% greater than in trees at the high elevation
      site.

PMID- 14972895
TI  - Photosynthesis, water relations and mortality in Abies lasiocarpa seedlings
      during natural establishment.
AB  - Few studies have investigated the ecophysiology of natural seedling establishment
      in forest trees not associated with anthropogenic disturbance. Photosynthesis and
      water relations measurements were made on one- through four-year-old seedlings of
      Abies lasiocarpa Nutt. (subalpine fir) establishing naturally in an understory
      environment. First (current)-year seedlings generally had only cotyledons,
      whereas most second-year seedlings had both cotyledons and primary leaves.
      Mortality was high (> 60%) in first-year seedlings with the greatest mortality (>
      90%) measured at the more open, sun-exposed sites within the understory. Seedling
      mortality was negligible after the first year of growth at shaded microsites and
      after the second year of growth at sunny microsites. Photosynthetic CO(2) uptake
      at light saturation was considerably lower in first-year than in fourth-year
      seedlings (0.6 micromol m(-2) s(-1) versus 1.7 micromol m(-2) s(-1)) and occurred
      at lower solar irradiance (240 micromol m(-2) s(-1) versus 600 micromol m(-2) s(
      1) of photosynthetically active radiation). Differences in photosynthetic
      capacity were due to differences in both stomatal and non-stomatal limitations to
      CO(2) uptake. Carbon dioxide assimilation in first- and second-year seedlings was
      28 and 29%, respectively, of the mean value measured for fourth-year seedlings.
      Although first-year seedlings had low transpiration rates, their water use
      efficiency (photosynthesis/transpiration) was less than half that of fourth-year
      seedlings and their water potentials were lower than those of all other age
      classes (0.46 mol CO(2) mmol(-1) H(2)O and -3.0 MPa, respectively). The stomatal
      limitation to CO(2) uptake was approximately 21% in first- and second-year
      seedlings, and increased to 39% in fourth-year seedlings. Intercellular CO(2)
      concentrations were greater in first- and second-year seedlings (255 and 250
      microl l(-1), respectively) than in third- and fourth-year seedlings (203 and 186
      microl l(-1), respectively). Thus, abrupt increases in water status and
      photosynthetic capacity after the first or second year of growth appear crucial
      for survival to maturity. Moreover, differences in temperature and water
      relations according to microsite may be major factors determining seedling
      establishment and, thus, the distributional and successional patterns observed
      for adult trees of Abies lasiocarpa.

PMID- 14972894
TI  - Winter desiccation and injury of subalpine red spruce.
AB  - Montane red spruce (Picea rubens Sarg.) in the northeastern United States has
      undergone a decline during the past two decades. One symptom associated with the
      decline syndrome is the episodic browning of first-year foliage in early spring.
      To examine the potential role of winter desiccation in this browning, the water
      relations of red spruce foliage in a subalpine forest on Mt. Moosilauke, New
      Hampshire, USA, were monitored from January to May, 1989. All sampled trees lost
      water during the winter and the first-year foliage on some trees turned brown in
      early spring. The relative water content of first-year shoots during the winter
      was a significant predictor of spring browning; red spruce trees that showed
      browning had desiccated faster and reached lower relative water contents. Damaged
      trees also had more closely packed needles and lower cuticular resistances to
      water loss. The first-year shoots had a significantly lower average relative
      water content than older shoots before and after browning. Cuticular resistance
      to water loss decreased with elevation. Sun-exposed shoots lost more water than
      shaded shoots because of solar heating of needles. Winter desiccation can occur
      before the decline-related spring browning of red spruce foliage.

PMID- 14972896
TI  - Sodium and chloride distribution in salt-stressed Prunus salicina, a deciduous
      tree species.
AB  - Measurements were made over four growing seasons of the Na(+) and Cl(-) content
      of leaves and woody tissues (twigs, branches, trunk and roots) of mature, fruit
      bearing Prunus salicina Lindl. (on Marianna 2624 rootstock) trees irrigated
      during the growing season with water containing 3, 14 or 28 mM salt (2/1 molar
      ratio of NaCl and CaCl(2)). At the beginning of the study, the trees were 19
      years old. Woody tissues of trees irrigated with water containing 14 or 28 mM
      salt accumulated Na(+) and Cl(-). Leaves of trees irrigated with water containing
      14 or 28 mM salt accumulated Cl(-), but not Na(+), unless they had visible
      symptoms of salt injury. X-Ray microanalysis of leaf mesophyll cells indicated
      some ability of the cells to sequester Cl(-) in the vacuole. The data demonstrate
      a capacity for ion compartmentation among tissues and cell organelles in mature
      Prunus salicina, which may explain the ability of the species to survive low
      levels of salinity for several years in the field.

PMID- 14972897
TI  - In vitro morphogenetic competence of basal sprouts and crown branches of mature
      chestnut.
AB  - Basal shoots of five clones of mature chestnut tree (Castanea sativa Mill. and C.
      sativa x C. crenata Siebold & Zucc.) had a greater capacity for in vitro
      establishment, multiplication and rooting than crown branches of the same trees.
      Cultures from basal shoots were more responsive than crown-derived cultures in
      terms of in vitro reactivity (proportion of the explants with shoot development),
      the mean number of shoots formed per explant, the length of the tallest shoot in
      each culture, and the multiplication coefficient (defined as the product of the
      reactivity and the mean number of shoots per explant). Multiplication
      coefficients were greatest between subcultures 6 and 12, but subculturing failed
      to increase the rooting potential of shoots of crown origin. Multiplication and
      rooting rates were also determined for clones derived from seeds of mature trees.
      Genotype influenced the in vitro performance of clones of both adult and seedling
      origins.

PMID- 14972898
TI  - Storage protein changes during zygotic embryogenesis in interior spruce.
AB  - The major storage proteins isolated from protein bodies of embryo tissues of
      interior spruce Picea glauca (Moench) Voss/Picea engelmanii Parry had apparent
      molecular weights of 41, 35, 33, 24 and 22 kD. Minor proteins of 30 and 27.5 kD
      were also observed. Based on their solubility characteristics, the 41 kD protein
      was identified as a water and buffer-soluble albumin, and the 35, 33, 24 and 22
      kD proteins were characterized as buffer-insoluble, high salt-soluble globulins.
      Two-dimensional electrophoresis revealed each protein was composed of several
      isoelectric variants. Developmentally specific accumulation of storage proteins
      was observed during embryogenesis. The 41 kD protein only accumulated during the
      later stages of cotyledon maturation, whereas the other storage proteins began to
      accumulate during the early stages of embryo development. All storage proteins
      showed major accumulations during cotyledon maturation.

PMID- 14972899
TI  - Acquired thermotolerance of jack pine, white spruce and black spruce seedlings.
AB  - The acquired thermotolerance of first-year seedlings of jack pine (Pinus
      banksiana Lamb.) hardened at 36, 38, 40 or 42 degrees C for 90, 180 or 360
      minutes and of black spruce (Picea mariana (Mill.) B.S.P.) hardened at 34, 36, 38
      or 40 degrees C for 30, 90, 180 or 360 minutes was determined by comparison of
      needle damage to that of non-hardened seedlings (25 degrees C) following exposure
      to temperatures of 49 and 47.5 degrees C, respectively. Compared to seedlings
      kept at 25 degrees C, heat injury sustained from exposure to high temperatures
      was markedly reduced following hardening for 180 minutes at 36 and 38 degrees C
      in jack pine and black spruce, respectively. Increasing the exposure time at 36
      degrees C in jack pine, and at 36 to 40 degrees C in black spruce, also reduced
      needle damage. The duration of increased thermotolerance was investigated in jack
      pine, black spruce and white spruce (Picea glauca (Moench) Voss) by comparing
      heat injury from high temperatures in non-hardened seedlings and in seedlings
      hardened at 38 degrees C for 180 minutes a day for either 1, 3 or 6 days. In all
      three species, the duration of acquired thermotolerance increased with the number
      of days of heat hardening. For jack pine and white spruce seedlings hardened at
      38 degrees C for 6 days, increased thermotolerance persisted for at least 14 and
      10 days, respectively, after the end of the hardening treatment. In contrast, the
      thermotolerance of black spruce seedlings hardened at 38 degrees C for 6 days
      remained elevated for only 4 days.

PMID- 14972900
TI  - The effect of different atmospheric ozone partial pressures on photosynthesis and
      growth of nine fruit and nut tree species.
AB  - Nursery stock of peach (Prunus persica L. Batsch, cv. O'Henry), nectarine (P.
      persica L. Batsch, cv. Fantasia), plum (P. salicina Lindel., cv. Casselman),
      apricot (P. armeniaca L., cv. Tilton), almond (P. dulcis Mill., cv. Nonpareil),
      prune (P. domestica L., cv. Improved French), cherry (P. avium L., cv. Bing),
      oriental pear (Pyrus pyrifolia Rehd., cv. 20th Century), and apple (Malus pumula
      Mill., cv. Granny Smith) were planted in open-top chambers on April 1, 1988 at
      the University of California's Kearney Agricultural Center located in the San
      Joaquin Valley (30 degrees 40' N 119 degrees 40' W). Trees were exposed to three
      atmospheric ozone partial pressures (charcoal-filtered air (C), ambient air (A),
      or ambient air + ozone (T)) from August 1 to November 17, 1988. The mean 12-h
      (0800 to 2000 h) ozone partial pressures measured in open-top chambers during the
      experimental period were 0.030, 0.051, and 0.117 microPa Pa(-1) in the C, A and T
      treatments, respectively. Leaf net CO(2) assimilation rate decreased linearly
      with increasing 12-h mean ozone partial pressure for the almond, plum, apricot,
      prune, pear, and apple cultivars. Stomatal conductances of apricot, apple,
      almond, and plum decreased linearly with increasing ozone partial pressure. Cross
      sectional area relative growth rates of almond, plum, apricot, and pear decreased
      linearly with increasing ozone partial pressure. Net CO(2) assimilation rate,
      stomatal conductance, and trunk growth of cherry, peach and nectarine were
      unaffected by the ozone treatments. Reduced leaf gas exchange probably
      contributed to ozone-induced growth reduction of the susceptible species and
      cultivars. Several of the commercial fruit tree species and cultivars studied
      were relatively tolerant to the ozone treatments.

PMID- 14972901
TI  - Climate change and forests.
AB  - Factors governing long-term change in global temperature are reviewed. The
      magnitude and rate of change in global temperature resulting from current
      increases in the concentration of atmospheric greenhouse gases are considered in
      relation to their impact on forests. Movement in forest zone boundaries at a rate
      of 2.5 km year(-1) are possible, which is nearly ten times the rate forests have
      been known to move by natural reproduction. Climate models indicate that
      increased global temperature will affect rainfall distribution, lead to more
      frequent and more severe storms and increase climatic variability. Consequences
      for the world's forests include increased frequencies of fire and blow-down, and
      wide-spread decline. Increased atmospheric CO(2) concentrations may increase
      forest growth where the effect is not offset by reduced precipitation, but the
      overall effect of anticipated changes in global climate is likely to be
      widespread loss of forests.

PMID- 14972902
TI  - Effects of leaf display on light interception and apparent photosynthesis in two
      contrasting Populus cultivars during their second growing season.
AB  - Effects of the contrasting leaf display of poplar cultivars Eugenei (Populus x
      euramericana) and Tristis (P. tristis x P. balsamifera) on light interception and
      photosynthesis were studied in the second year of growth in an irrigated
      plantation near Rhinelander, Wisconsin, USA (lat. 45 degrees N). Leaves on the
      current terminal (CT) and on proleptic branches were measured between 0900 and
      1500 h on five clear days from June to September 1980. Leaf orientation-based
      differences between these cultivars were evident as the second growing season
      progressed and the crowns of the trees in the plantation grew together. Leaves of
      Eugenei are erectophile or tilted from the horizontal. In this cultivar light
      penetrated throughout the crown; many leaves on the lowest branches were
      illuminated as fully as those on the upper CT and had higher photosynthetic rates
      than equivalent leaves in Tristis. However, by early September many of the lower
      branches on Eugenei trees had abscised. In the planophile Tristis, adaxial photon
      flux densities (PPFD) of leaves on the lower portion of the CT and on branches
      were only a fraction of those measured on the upper CT. This pattern became more
      extreme as the season progressed. Few of the lower branches of Tristis abscised
      during the growing season. Photosynthesis rates, especially on a whole-leaf
      basis, were closely related to incident PPFDs in both cultivars. The ecological
      significance of these results are discussed, as well as the hypothesized effect
      of leaf inclination on crop productivity.

PMID- 14972903
TI  - Autumn coloring, photosynthetic performance and leaf development of deciduous
      broad-leaved trees in relation to forest succession.
AB  - Autumn coloring of deciduous broad-leaved trees in northern Japan was found to
      develop either from the inner part of the crown outward (inner-type), or from the
      outer part of the crown inward (outer-type). Inner-type trees had early
      successional characteristics, whereas outer-type trees had late-successional
      characteristics. Although alders (Alnus hirsuta (Spach) Rupr. and A. japonica
      (Thunb.) Steud.) did not change color in the fall, these early-successional
      species were also studied. Both chlorophyll content and chlorophyll a/b ratio
      increased then decreased with increasing leaf age. In early fall, however,
      chlorophyll content of leaves on the same branch decreased from older to younger
      leaves only in the inner-type species. Net photosynthetic rates at light
      saturation of individual leaves increased then decreased at a greater rate in
      inner-type species than in outer-type species. Leaf dry weight per unit area
      decreased more before leaf fall in outer-type species than in inner-type species.
      Inner-type species have younger leaves at the outer surface of crowns, whereas in
      outer-type species, leaf age is similar throughout the crown. Leaf senescence of
      outer-type species began in the outer surface of crowns. The pattern of leaf
      senescence and the development of fall colorations may be related to the growth
      strategy of the species.

PMID- 14972904
TI  - Exploring the relationship between reflectance red edge and chlorophyll content
      in slash pine.
AB  - Chlorophyll is a key indicator of the physiological status of a forest canopy.
      However, its distribution may vary greatly in time and space, so that the
      estimation of chlorophyll content of canopies or branches by extrapolation from
      leaf values obtained by destructive sampling is labor intensive and potentially
      inaccurate. Chlorophyll content is related positively to the point of maximum
      slope in vegetation reflectance spectra which occurs at wavelengths between 690
      740 nm and is known as the "red edge." The red edge of needles on individual
      slash pine (Pinus elliottii Engelm.) branches and in whole forest canopies was
      measured with a spectroradiometer. Branches were measured on the ground against a
      spectrally flat reflectance target and canopies were measured from observation
      towers against a spectrally variable understory and forest floor. There was a
      linear relationship between red edge and chlorophyll content of branches (R(2) =
      0.91). Measurements of the red edge and this relationship were used to estimate
      the chlorophyll content of other branches with an error that was lower than that
      associated with the calorimetric (laboratory) method. There was no relationship
      between the red edge and the chlorophyll content of whole canopies. This can be
      explained by the overriding influence of the understory and forest floor, an
      influence that was illustrated by spectral mixture modeling. The results suggest
      that the red edge could be used to estimate the chlorophyll content in branches,
      but it is unlikely to be of value for the estimation of chlorophyll content in
      canopies unless the canopy cover is high.

PMID- 14972905
TI  - Influence of male and female cones on assimilate production of Pinus contorta
      trees within a forest stand.
AB  - Studies on branches of field-grown Pinus contorta Dougl. trees showed that: (i)
      branches with fully developed male or female cones were heavier than vegetative
      branches; (ii) the production of female cones decreased neither the number of
      laterals nor the length of the terminal or lateral shoots on the cone-bearing
      branches; (iii) the production of male cones decreased both the number of
      laterals and the number of needles on the cone-bearing branches; (iv) needles on
      male cone-bearing branches had significantly higher photosynthetic rates and
      needles on female cone-bearing branches generally also fixed more CO(2) per
      quantum of light. In addition, both male and female cones refixed a significant
      proportion of respired CO(2) when illuminated. The simulation model, MAESTRO, was
      used to estimate light penetration through two stands (3690 and 1845 trees ha(
      1)) of P. contorta trees and to calculate the resultant CO(2) assimilation of a
      vegetative, a male and a female cone-bearing tree on sunny, partly sunny and
      cloudy days in Scotland. Generally, the CO(2) efflux from female cones was less
      than 3% of the CO(2) assimilated by the whole tree. The presence of male cones
      resulted in an average 33% decrease in needle complement, but an increased
      quantum efficiency of associated needles in the autumn. It was estimated that, on
      a sunny day, male cone-bearing trees assimilated as much CO(2) as vegetative
      trees in the high density stand and only 6% less in the low density stand. On
      cloudy days, the smaller needle complement was beneficial to the carbon economy
      of the tree because of lower respiration losses compared with a vegetative tree.

PMID- 14972906
TI  - Distribution and metabolism of current photosynthate by single-flush northern red
      oak seedlings.
AB  - Carbon distribution and metabolism by northern red oak seedlings (Quercus rubra
      L.) were followed for 72 h after a 30-min photosynthetic exposure to (14)CO(2).
      Approximately 50% of the assimilated carbon was lost during this time, presumably
      through respiration. Most of the (14)C recovered in the plant remained in the
      source leaf. Most of the exported (14)C was found in stems and especially roots.
      Position of the source leaf did not affect distribution of translocated (14)C;
      however, upper source leaves retained slightly more (14)C than lower source
      leaves. Most (14)C in all tissues was found initially in sugars. Labeled carbon
      in this fraction decreased rapidly and increased in other chemical fractions,
      particularly residue (structural carbohydrates and lignin). More (14)C was
      incorporated into residue than into any other chemical fraction, indicating
      continued growth by each of the tissues during the lag stage of seedling
      development. Labeled carbon increased in proteins for 6 to 12 h after treatment,
      then remained essentially constant for the remainder of the transport period,
      indicating both rapid incorporation of the pulsed (14)C into, and slow turnover
      of, the labeled protein components. In source leaves, (14)C incorporated into
      starch in the light was lost during the dark period, a typical diurnal storage
      pattern. In stems, (14)C in starch increased for 12 h, then decreased during the
      dark period, and then increased during the rest of the transport period. This
      pattern indicates that stems have both diurnal and long-term storage pools of
      starch. In roots, (14)C in starch increased rapidly for 12 h, then remained
      constant for the rest of the transport period, indicating primarily long-term
      storage in this tissue. Peak (14)C in amino acids in taproot preceded that in
      stem tissue, indicating recycling of (14)C from the roots to the shoot in amino
      acids.

PMID- 14972907
TI  - Whole-tree carbon and nitrogen partitioning in young hybrid poplars.
AB  - The effects of water, nitrogen (N), and genotype on whole-tree carbon and
      nitrogen partitioning were examined in two Populus genotypes grown from cuttings
      in large pots set in the ground. Four replicate trees from each genotype/water/N
      treatment combination were harvested in either August, September, or November of
      their first year of growth. Aboveground biomass was linearly related to total
      leaf area. Clones allocated photosynthate differently. Populus tristis x P.
      balsamifera cv. Tristis #1 produced 14.5 cm of fine roots (< 0.5 cm diameter) per
      cm(2) of foliage, whereas P. x euramericana cv. Eugenei only produced 4.0 cm of
      fine roots per cm(2) of foliage. The large diameter structural roots of Eugenei
      grew rapidly late in the growing season so that large-root biomass was 3.8 to 7.5
      times greater in November than in mid-August. In both clones, the root system
      grew twice as fast as the stem and branches late in the year. During August,
      about 75% of total tree N was in the canopy, but at least 80% of the September N
      content was still present in November following leaf fall. The major site of N
      storage was the large diameter structural roots. Nitrogen concentrations in these
      roots doubled following bud set.

PMID- 14972908
TI  - Late-season changes in allocation of starch and sugar to shoots, coarse roots,
      and fine roots in two hybrid poplar clones.
AB  - Two hybrid Populus clones, Tristis and Eugenei, which had been grown from
      cuttings in 114-liter pots sunk in the ground, were sequentially harvested during
      the latter part of the first growing season. Pots were supplied with water and
      nitrogen at two different rates. Starch and sugar concentrations were determined
      in samples taken from stems, branches, cuttings, and five diameter classes of
      roots. Concentrations of starch and sugar in all components of the trees were
      significantly affected by time of harvest and clone. Water and nitrogen
      treatments, however, did not significantly affect carbohydrate concentrations.
      From August to November, as plants developed cold hardiness, starch
      concentrations declined and sugar concentrations increased in stems and branches,
      especially in Tristis. In both clones, the large roots (> 1 mm diameter) were
      major repositories of starch and sugar late in the season. By the end of
      September, 80% of total-tree nonstructural carbohydrates in Eugenei were located
      in the roots. Even the fine-root fraction (< 0.5 mm diameter) showed substantial
      carbohydrate loading in late season, contradicting the hypothesis that starch
      deposition in fine roots occurs only when they are being formed.

PMID- 14972909
TI  - Plant area index in Eucalyptus globulus plantations determined indirectly by a
      light interception method.
AB  - Plant area index (PAI) was estimated in 3-year-old plantations of Eucalyptus
      globulus Labill. from (i) allometric relationships obtained from biomass
      harvesting, and (ii) canopy transmittance measurements. Diffuse light canopy
      transmittance was measured with a multi-cone sensor consisting of five inverted
      cones to scan a hemisphere. Plant area index was calculated from transmittance
      measurements by the inversion method assuming an ellipsoidal angle distribution
      of uniformly distributed canopy elements, or by application of the Beer-Lambert
      Law using an empirically determined extinction coefficient (k) for diffuse light
      of 0.5. Plant area index values of the experimental plantations varied as a
      consequence of diffferent water and mineral nutrient application rates. The PAI
      estimated from biomass harvesting ranged from 1.61 to 4.04. The estimates of PAI
      obtained by the ellipsoidal angle distribution method were significantly
      different from those based on the allometric relationships or from transmittance
      measurements assuming a value of k for diffuse light of 0.5.

PMID- 14972910
TI  - Estimation of leaf area index in fourteen southern Wisconsin forest stands using
      a portable radiometer.
AB  - Projected leaf area index (LAI) and Beer-Lambert Law extinction coefficients (K)
      were estimated for 28-year-old Picea abies (L.) Karst., Larix decidua Mill.,
      Pinus resinosa Ait., and Pinus strobus L. plantations using vertical profile data
      obtained with a portable integrating radiometer (sunfleck ceptometer). Predicted
      LAI values were compared with direct measures of LAI. Based on dimensional
      analysis, LAI ranged from 5.0 for Larix decidua to 10.5 for Picea abies.
      Significant inverse relationships between cumulative LAI and canopy transmitted
      radiation were observed for the four species (R(2) = 0.92-0.97). Beer-Lambert
      extinction coefficients ranged from 0.39 for Picea abies to 0.84 for Pinus
      strobus. Stand-level predictions of LAI based on the Beer-Lambert Law were
      compared with measured LAI values for eight conifer and six broadleaf stands.
      Using local K estimates resulted in predicted LAI values with an average 6%
      error. Using published K values resulted in an average error of 20%. High LAI and
      concomitantly low light levels below the canopy of Picea abies stands resulted in
      large overestimation errors in predicted LAI, rendering the sunfleck ceptometer
      inappropriate for forests with large LAIs.

PMID- 14972911
TI  - Assessing seasonal leaf area dynamics and vertical leaf area distribution in
      eastern white pine (Pinus strobus L.) with a portable light meter.
AB  - We evaluated the ability of a portable light meter (Sunfleck Ceptometer, Decagon
      Devices, Pullman, WA, USA) to quantify seasonal photosynthetically active
      radiation (PAR, 400-700 nm) interception, projected stand leaf area index (LAI),
      and vertical LAI distribution in a 32-year-old eastern white pine (Pinus strobus
      L.) plantation. Canopy PAR transmittance measured with the ceptometer was
      converted to LAI with the Beer-Lambert Equation. The ceptometer was sensitive to
      changes in PAR transmittance resulting from foliage growth. Predicted stand LAI
      ranged from 3.5 in the dormant season to a maximum of 5.3 in late July. Predicted
      LAI values were within 9% of values determined from destructive sampling.
      Published canopy extinction coefficients (k) were inadequate for converting PAR
      transmittance data to stand LAI because a significant amount of PAR was
      intercepted by dead branches and stems below the forest canopy. Because of
      interception by dead branches and stems, we estimated k = 0.84, which is
      substantially higher than previously reported values. The ceptometer was also
      sensitive to seasonal changes in PAR transmittance within the canopy. However, in
      contrast to predictions based on the Beer-Lambert Law, the relationship between
      proportional PAR transmittance (Q(i)/Q(o)) and cumulative LAI within the canopy
      was linear. Thus, vertical LAI distribution was best estimated with a linear
      model, as opposed to the non-linear model assumed in the Beer-Lambert Equation.
      We hypothesize that the linear relationship was a result of a gap in the canopy
      which was not represented by the cumulative leaf area distribution estimation
      procedure.

PMID- 14972912
TI  - Architectural distribution of foliage in individual Pinus radiata D. Don crowns
      and the effects of clumping on radiation interception.
AB  - The architectural arrangement and leaf area of representative branch units, on
      one branch complex from each cluster on the stem, were measured on six trees in a
      widely spaced 7-year-old Pinus radiata D. Don plantation. There was a linear
      relationship between leaf area and the basal area of branch complexes. Assuming
      similarity in the arrangement of branch units within concomitant branch complexes
      at each cluster, the 3-dimensional distribution of leaf area density (leaf area
      per unit volume) in an array of cubic cells, each 10(-3) m(3), comprising the
      volume of each tree crown, was reconstructed. The fraction of cells in which
      foliage was present varied from 0.08 to 0.23 in the crowns with the highest (Tree
      4) and lowest (Tree 3) degree of clumping, respectively. This difference was
      related to the number, length, and leaf area per unit length of Order 3 branch
      units, in particular. The actual distributions of leaf area density were used
      with a simple radiative transfer model to estimate the probability of penetration
      of beam and diffuse photosynthetically active radiation (PAR) through individual
      tree crowns. The average probability of beam penetration was greater for the tree
      with the most clumped foliage than for the tree with the least clumped foliage.
      For both trees, the average probabilities of penetration were greater than the
      values that would have resulted if a random distribution of foliage had been
      assumed. The negative binomial model was used to estimate an index of foliage
      dispersion for the tree crowns. For beam PAR, the index of foliage dispersion was
      3.3 and 2.3 for the trees with the most, and the least clumped foliage,
      respectively. These results were supported by analysis of the architectural
      arrangement of foliage in the tree crowns. For two days in summer, the assumption
      that leaf area density was randomly distributed would have resulted in a 20 to
      30% overestimation of intercepted PAR flux by the tree crowns.

PMID- 14972913
TI  - Crown architecture of Populus clones as determined by branch orientation and
      branch characteristics.
AB  - Crown architecture, including branching pattern, branch characteristics and
      orientation of proleptic and sylleptic branches was studied in five poplar clones
      (Populus deltoides, P. trichocarpa and P. trichocarpa x P. deltoides hybrids),
      grown under intensive culture in the Pacific Northwest, USA. Branch
      characteristics measured were number, length, diameter, biomass and the angles of
      origin and termination. The results suggest that genotype has a major influence
      on crown architecture in Populus. Clonal differences in branch characteristics
      and branching patterns were found that resulted in striking differences in crown
      form and architecture. Branch angle and curvature differed significantly among
      clones, and among height growth increments within clones. Branch length and
      diameter were significantly correlated in all clones. Sylleptic branches and the
      considerable leaf area they carry have important implications for whole tree
      light interception, and thus, play a critical role in the superior growth and
      productivity of certain hybrid poplar clones. The considerable variation in
      branch characteristics implies a strong justification for including them in
      selection and breeding programs for Populus.

PMID- 14972914
TI  - A quantitative analysis of stem form and crown structure: the S-curve and its
      application.
AB  - The statical model of Oohata and Shinozaki (1979) was applied to derive a whole
      stem form function for Cryptomeria japonica D. Don, Chamaecyparis obtusa Endl.,
      and Larix leptolepis Gordon. Defining stem density (weight per unit length) at a
      depth z from the tree top as S(z), the relationships between the total stem
      weight T(s)(z) from the apex to the z-horizon and S(z) were examined. A formula
      with two exponential functions, corresponding to the stem form above and below
      the crown base, was obtained. This formula was termed the "S-curve." Applying the
      same analysis to the total weight of a branch and the weight of a unit length (10
      cm) at the branch base yielded a similar curve. This result suggests that the
      formula for branch form can be determined from a single branch in a forest stand.
      It also provides quantitative evidence of the fractal structure of trees.

PMID- 14972915
TI  - Dependence of some stand characteristics on stand density.
AB  - The development of stand basal area at the height of the lowest living branch was
      studied in four Norway spruce (Picea abies L. Karst.) plantations subjected to
      various levels of thinning. Crown limit basal area (defined as the sum of the
      cross-sectional areas of stems estimated at the base of the living crown per
      hectare) increased after each thinning until it matched that of unthinned plots.
      In unthinned plots, the crown limit basal area remained constant during the 26
      year period of study. The dependence of the logarithm of stem number on the
      logarithm of the mean stem diameter at breast height was curved and dependent on
      the degree of thinning. The dependence of the logarithm of stem number on the
      logarithm of the mean stem diameter at crown height was linear and slightly
      dependent on the degree of thinning. This dependence can be used as the self
      thinning rule.

PMID- 14972916
TI  - Reconstructed development of stem production and foliage mass and its vertical
      distribution in Japanese larch.
AB  - Hypotheses of independence with time in (1) height growth rate, (2) crown length,
      (3) total foliage mass, and (4) vertical profile of foliage mass density within a
      crown following canopy closure were tested with two codominant trees in a 15-year
      old Japanese larch (Larix kaempferi (Lamb.) Carr.) plantation by means of a
      combined method consisting of detailed stem analysis (to reconstruct development
      of stem growth over time), knot dissection (to identify time of branch
      mortality), and a stem diameter versus cumulative foliage mass relationship at a
      given stem location. I failed to reject all hypotheses at the 5% significance
      level. All parameters converged to constant values after canopy closure. Foliage
      efficiency for stem volume density production also assumed a constant value.
      Vertical profiles of the foliage mass density did not change after crown closure;
      however, the profile for one tree showed a more heterogeneous distribution
      because of the presence of large branches. Implications of these results for the
      profile diagram model of tree growth (Chiba et al. 1988, Osawa et al. 1990) are
      discussed.

PMID- 14972917
TI  - Characteristics of normal-crowned and pendula spruce (Picea abies (L.) Karst.)
      examined with reference to the definition of a crop tree ideotype.
AB  - Sixty-four 19-year-old Norway spruce trees were felled and the roots excavated
      during 1987 and 1988. The trees were open-pollinated progenies from a small stand
      located in southern Finland. Several characteristics of stem, crown, and roots
      were measured and analyzed on 36 pendula and 28 normal-crowned trees in the
      sample. Total fresh weight, stem fresh weight, and crown fresh weight were 47.6,
      27.5, and 61.4% greater in normal-crowned trees than in pendula trees. The mean
      harvest index (including roots) of pendula spruce was 0.32 compared with a value
      of 0.27 for normal-crowned trees. This difference reflects the difference in
      crown biomass between the two groups of trees. The crown structure of pendula
      spruce appears to permit higher stand densities than is possible with normal
      crowned spruce. Thus the results indicate that genetically narrow-crowned trees
      with a small total crown mass could provide useful basic material for selection
      of crop trees with a high stemwood production per hectare.

PMID- 14972918
TI  - The interaction between leaf longevity and shoot growth and foliar biomass per
      shoot in Pinus contorta at two elevations.
AB  - Leaf longevity ranged from an average of 5 to 18 years in individual trees of
      lodgepole pine (Pinus contorta Dougl. ssp. latifolia D.K. Bailey) from six even
      aged stands in central Colorado, USA, of which three were at an elevation of 2800
      and three at an elevation of 3200 m. Leaf longevity was 38% greater and annual
      shoot growth increment was 33% less in trees growing at 3200 m than in trees
      growing at 2800 m elevation. There was no difference in leaf biomass per shoot
      between the trees at the two elevations. These results suggest that leaf
      longevity is greater on shoots with low annual growth potential. Thus, a slow
      growing tree at high elevation (low annual shoot growth potential) can have the
      same amount of foliage per shoot as a fast-growing tree at lower elevation. This
      plasticity in leaf longevity enables a consistency in foliar biomass per shoot,
      which may contribute to the wide range of sites and environments that lodgepole
      pine occupies successfully.

PMID- 14972919
TI  - Gas exchange in Quercus rubra (northern red oak) during a drought: analysis of
      relations among photosynthesis, transpiration, and leaf conductance.
AB  - Development of water stress in leaves of mature Quercus rubra L. caused a marked
      midday depression in photosynthesis (A) and transpiration (E). At external CO(2)
      partial pressures of 100-110 Pa, a constant temperature of 30 degrees C and a
      constant photosynthetic photon flux density of about 1000 micromol m(-2) s(-1), A
      was 8 micromol m(-2) at low leaf water potentials (-1.5 to -2.0 MPa), whereas it
      was 20 micromol m(-2) s(-1) in non-stressed leaves (-1.0 MPa). At lower external
      CO(2) partial pressures, the effect of low leaf water potential on A was less.
      The midday depression in gas exchange was relieved by an overnight rain of 2.5
      cm. No difference in carboxylation efficiency or CO(2) compensation point was
      found between leaves before and after rain, The relationship between A and E was
      linear for a given external CO(2) partial pressure, but the slope varied with
      CO(2) concentration. Modification of the model of stomatal response proposed by
      Ball et al. (1987) produced a linear relationship between leaf conductance and a
      factor incorporating A, relative humidity, and CO(2). The data indicate that gas
      exchange in leaves of mature northern red oak respond rapidly to relief of
      drought with no indication of long-term photoinhibition.

PMID- 14972920
TI  - Adaptations and responses to drought in Quercus species of North America.
AB  - Most North American oaks (Quercus spp.) are adapted to drought-prone sites by an
      ability either to avoid, or to tolerate, water stress, or both. Generally, they
      have deep-penetrating root systems, enabling them to maintain relatively high
      predawn water potentials during drought. Oaks have thick leaves and some have
      relatively small stomata, both characteristics that favor high water use
      efficiency. However, some species, from warm regions, have large stomatal pores.
      The rapid evaporative cooling made possible by large stomata, may be an
      adaptation to high temperature. Some southeastern species display leaf curling
      during drought, and Q. douglasii a native of California is drought deciduous.
      Oaks have a ring-porous xylem anatomy, allowing rapid sap movement in large
      diameter, early-wood vessels when soil water is plentiful, and slower, but
      sustained, water movement in narrower, late-wood vessels, which are more
      resistant to cavitation, during drought. Oaks frequently maintain a higher rate
      of photosynthesis at low leaf water potentials and high vapor pressure deficits
      than co-occurring species of other genera. An exception is Quercus rubra, which
      is generally restricted to relatively mesic sites. During drought, many oak
      species, especially those native to arid regions, undergo changes in tissue
      osmotic potential. However, it remains to be shown whether such changes are
      phenological or drought induced. Reported values for bulk modulus of elasticity
      vary widely among species and studies, and have been observed to both increase
      and decrease during drought in a way that is unrelated to region or to changes in
      predawn water potential or osmotic potential. Diurnal leaf water potential during
      drought is probably a poor indicator of differences among oak species in gas
      exchange rate, because of interspecific variation in desiccation avoidance and
      tolerance.

PMID- 14972921
TI  - Characteristics of high- and low-vigor lodgepole pine trees in old-growth stands.
AB  - Lodgepole pine (Pinus contorta var. latifolia Engelm.) trees in an old stand
      differed widely in appearance. Some appeared healthy, with deep crowns, high leaf
      areas, nearly conical-shaped crown tops, and branches with live needles extending
      well back from the tip. Others with similar-sized boles appeared to be in a state
      of decline, having much shallower crowns, lower leaf areas, crowns that were
      flattened at the top, and "tufted" branches with needles only near the ends of
      the branches. Ten trees, five each in these two apparent vigor classes, were
      selected from a one-hectare area of a mature stand. Trees in the two groups were
      found to have similar height, diameter at breast height, age, and total volume.
      As expected from the selection criteria, high-vigor trees had much deeper crowns
      (P = 0.01) and higher leaf areas (P = 0.10). The volume of heartwood in the bole
      was higher in the low-vigor trees (P = 0.08), and the volume of the sapwood was
      higher in the high-vigor trees (P = 0.13). Sapwood and heartwood ages were
      similar in both classes. This suggests that, in earlier years, low-vigor trees
      reached a larger volume, represented by the present heartwood, than did the high
      vigor trees (i.e., the current vigor rankings are the reverse of what they had
      been). The ratio of sapwood volume to total leaf area was not significantly
      higher in the low-vigor trees (P = 0.24), although this ratio varied tenfold
      among the data. Results suggest that a physiological basis for assessing vigor
      involving leaf area, sapwood, heartwood, age, and incremental growth data would
      identify a continuum of response from high- to low-vigor trees rather than
      discrete groups based on visual appearance.

PMID- 14972922
TI  - Interactive effects of resource availabilities and defoliation on photosynthesis,
      growth, and mortality of red oak seedlings.
AB  - Responses of forest trees to defoliation by insects such as gypsy moth vary
      greatly from site to site and from individual to individual. To determine whether
      some of this variation could be explained by variation in other stress factors,
      red oak (Quercus rubra L.) seedlings were exposed to low and high light, water,
      mineral nutrient, and defoliation treatments, in a complete factorial design in a
      greenhouse. Significant interactions were observed among factors for
      photosynthesis, growth, and mortality, indicating that the response to
      defoliation was influenced by other stresses. Defoliation increased the
      photosynthetic capacity per unit leaf area of seedlings grown in the low-water,
      but not in the high-water, regime. In response to defoliation, growth of
      seedlings in a low-mineral-nutrient, or low-light, regime was depressed less than
      that of seedlings grown in a high-mineral-nutrient, or high-light, regime.
      However, defoliation resulted in a similar percent reduction in biomass in all
      seedlings in both the high and the low light, water, and mineral nutrient
      treatments. Defoliation-induced mortality of shaded plants was twice that of
      plants grown in full sun.

PMID- 14972923
TI  - ECOPHYS: An ecophysiological growth process model for juvenile poplar.
AB  - The ECOPHYS model is an ecophysiological growth process model of juvenile poplar
      clones growing under near optimal conditions. The theoretical basis for the
      ECOPHYS model is that (1) individual leaves drive and control growth; (2) the
      microenvironment at the leaf exerts primary control of photosynthetic rates; (3)
      leaf orientation is a major determinant of that microenvironment, (4)
      photosynthates produced by leaves are allocated among meristematic and
      respiratory sinks: and (5) the plant's genome and microenvironment regulate
      photosynthate allocation. The major driving variables are solar radiation,
      temperature, and clonal morphological and physiological factors. The user can
      interact or override any or all of the input variables to examine the effects of
      such changes on photosynthetic production and growth. Verification and
      sensitivity analyses of ECOPHYS are presented and discussed. The use of ECOPHYS
      as a research tool is illustrated with several examples. Model potential and
      limitations are discussed.

PMID- 14972924
TI  - Validation of photosynthate production in ECOPHYS, an ecophysiological growth
      process model of Populus.
AB  - A model of photosynthate production is the central component of a larger whole
      tree ecophysiological growth process model for Populus (ECOPHYS). This
      photosynthesis model was validated by comparing predicted photosynthate
      production values for individual leaves and the total tree with hourly field
      measurements collected on four days spaced throughout a growing season. Simulated
      trees had identical numbers of leaves and leaf areas as the sample trees studied
      in the field, and hourly weather data collected on the plantation site were
      supplied as a model input. Total production for the four sample days ranged
      between 200 and 4900 mg CO(2) tree(-1) day(-1). Model predictions of total daily
      photosynthate production were within 12% of the observed rates for three of the
      four sampling days. Diurnal variations in stomatal conductance and ambient CO(2)
      concentrations and seasonal variations in area leaf weight were the primary
      sources of error. Total leaf area, proportion of sunlit leaf area, and
      photosynthetic efficiency were the most important factors influencing carbon
      dioxide exchange rates.

PMID- 14972925
TI  - Influence of crown structural properties on PAR absorption, photosynthesis, and
      transpiration in Sitka spruce: application of a model (MAESTRO).
AB  - The structure of a tree crown can be described by the spatial distribution,
      inclination, and orientation of all the phytoelements (leaves, twigs, branches,
      trunk, etc.), and their geometric properties. The following four structural
      properties have been studied in relation to radiation absorption, photosynthesis,
      and transpiration using a simulation model named MAESTRO: crown shape, total area
      of leaves and their spatial distribution within the tree crown, and the leaf
      inclination angle distribution. It was found that the total area of leaves and
      their spatial distribution within the tree crown are far more important than the
      other two properties for radiation absorption, photosynthesis, and transpiration.

PMID- 14972926
TI  - Relationship between canopy depth and other dimensions of coastal Pinus
      thunbergii Parlat. forests in Japan.
AB  - The relationship between canopy depth and other dimensions of coastal Pinus
      thunbergii Parlat. forests was analyzed from data for 29 stands using a
      mathematical model describing canopy depth. The model was derived from the
      relationship between mean diameter at breast height (D) and mean tree height (H).
      Maximum mean tree height (H(max)), which was calculated as H(max) = AD(B) where A
      and B are parameters, approximated the upper 95 percentile of H for a given D.
      Maximum canopy depth (L(cmax)) was calculated as L(cmax) = H(max) - H(B), where
      H(B) is mean clear length. Relative maximum canopy depth (R(cmax); defined as
      L(cmax)/H(max)) was approximated as 1/R(cmax) = 1/(aS(R) (b)) + 1, where a and b
      are parameters. The term S(R) was defined as N(-1/2)/H, where N is stand density
      (trees m(-2)). From these equations, the canopy depth (L(c))was derived as L(c) =
      H - H(max)/(aS(R) (b) + 1), because L(c) = H - H(B). From these relationships a
      diagram showing possible points of regulation of canopy depth was developed.

PMID- 14972927
TI  - Vertical variation in canopy structure and CO(2) exchange of oak-maple forests:
      influence of ozone, nitrogen, and other factors on simulated canopy carbon gain.
AB  - Stand-level and physiological measurements were made for oak and maple species
      common in Wisconsin forests. Scaling relationships were identified to allow the
      development of a model for estimating net carbon exchange at the levels of a
      leaf, canopy stratum, and whole canopy. Functional relationships were determined
      between tissue gas exchange rates and perceived controlling variables. Vertical
      variation in leaf properties and in the distribution of foliage by weight, area,
      and species were characterized for several closed canopy forests. Forest canopies
      were divided into four horizontal strata to develop predictive models for canopy
      gas exchange. Leaf and canopy layer carbon dioxide exchange rates were predicted
      using leaf nitrogen concentration, leaf mass per area, ozone exposure, predawn
      leaf water potential, photosynthetically active radiation, and vapor pressure
      deficit as driving variables. Direct measurements of leaf gas exchange were used
      to validate the components (subroutines) of the model. Net carbon dioxide
      exchange was simulated for canopy layers at 5-min intervals over a diurnal time
      course. Simulations of canopy CO(2) exchange were made for a 30-m tall, mixed oak
      maple forest under hypothetical ambient and greater-than-ambient ozone pollution
      regimes. Daily canopy net CO(2) exchange was predicted for seven forest stands
      and compared with estimates of aboveground net primary production, N
      availability, leaf area index, and canopy N.

PMID- 14972928
TI  - Comparison of three cold hardiness tests for conifer seedlings.
AB  - Greenhouse-cultured, container-grown ponderosa pine (Pinus ponderosa var.
      scopulorum Engelm.), interior Douglas-fir (Pseudotsuga menziesii var. glauca
      (Beissn.) Franco), and Engelmann spruce (Picea engelmannii (Parry) Engelm.) were
      cold acclimated and deacclimated in growth chambers over 19 weeks. Cold hardiness
      was measured weekly by a whole-plant freeze test and by two quick tissue tests:
      freeze-induced electrolyte leakage of needles, and differential thermal analysis
      of buds. The whole-plant freeze test provided results in 7 days, and indicated
      differences in cold hardiness among stems, buds, and needles. Although the whole
      plant freeze test could accurately measure cold hardiness, it was not precise,
      and it required destructive sampling. Results from freeze-induced electrolyte
      leakage and differential thermal analysis were available in 2 days and 1 hour,
      respectively. The freeze-induced electrolyte leakage test was a precise,
      sensitive and objective predictor of changes or differences in tissue cold
      hardiness. To determine actual cold hardiness, results could be calibrated to the
      response of the same tissue in the whole-plant freeze test. The speed and
      objectivity of differential thermal analysis made this test useful for rapid,
      general assessment of cold hardiness status, but calibration was difficult, and
      precision varied.

PMID- 14972929
TI  - Changes in the water relations of balsam fir and white birch saplings after
      thinning.
AB  - In the autumn of 1987, young balsam fir (Abies balsamea (L.) Mill.) and white
      birch (Betula papyrifera Marsh.) trees were thinned and their water relations
      followed during the next two growing seasons. At the beginning of the first
      summer following treatment, thinned trees of both species had lower osmotic
      potentials at full saturation (Psi(pi,sat)) and at turgor loss point
      (Psi(pi,tlp)) compared with controls. At this time, Psi(pi,sat) was linearly
      related to the percentage of full sunlight reaching the trees. A higher sugar
      concentration in leaves was an important component of the lower Psi(pi,sat) of
      thinned trees. For the other two sampling dates during the first growing season
      after treatment and all three sampling dates during the second growing season
      after treatment, little osmotic adjustment of the thinned trees relative to the
      control tress was observed in either species. The absence of osmotic adjustment
      during the second growing season following thinning suggests that other
      mechanisms were responsible for the acclimation of the treated trees to the
      higher atmospheric evaporative demand. Sapwood permeability (k) of white birch
      was higher than that of balsam fir, but no differences in k or in sapwood area
      were found between treated and control trees of either species. Predawn water
      potentials (Psi(pred)) of treated trees were less negative than those of
      controls.

PMID- 14972930
TI  - Inherited narrow crown form, harvest index and stem biomass production in Norway
      spruce, Picea abies.
AB  - The effect of crown form on stem biomass production was investigated in an 18-19
      year-old Norway spruce stand (Picea abies (L.) Karst.). The harvest index was
      0.271 in pendula trees, which have a heritable narrow crown form, and 0.235 in
      normal-crowned trees and the dry weights of stem biomass were 2.57 kg and 3.37
      kg, respectively. However, the production of stem biomass per crown projected
      area was more than twice as much in pendula trees as in normal-crowned trees.
      Results indicate that the crown form of pendula spruce is less plastic than that
      of normal-crowned spruce suggesting that such trees might maintain a high
      stemwood yield per unit ground area with increasing stand density. Because
      pendula spruce has a higher harvest index and a less flexible crown than normal
      crowned spruce, it might be useful for crop tree ideotype breeding.

PMID- 14972931
TI  - Xylem dysfunction in Quercus: vessel sizes, tyloses, cavitation and seasonal
      changes in embolism.
AB  - The seasonal progression of xylem dysfunction from tyloses and embolism induced
      both by cavitation and frost was studied in Quercus rubra L. and Quercus alba L.
      branches. Vessel lengths and diameters were measured in current-year rings of
      branches of various ages. Vessels in current-year shoots are about the same size
      as those in many diffuse porous trees, but vessels in older branches are two to
      six times larger in diameter and typically more than 10 times longer. Large
      Quercus vessels were more vulnerable to cavitation than small vessels. The small
      vessels in current-year shoots were more vulnerable to cavitation than vessels of
      comparable size in diffuse porous species. Earlywood vessels are completely
      blocked by tyloses within a year of their formation. Tylose growth starts in
      winter, but the vessels are not fully blocked until the next summer. Many
      latewood vessels, by contrast, remain free of complete blockage for several
      years. In Q. rubra, loss of hydraulic conductivity in current-year shoots due to
      cavitation reaches 20% by August and > 90% after the first hard frost. Both
      laboratory and field observations confirm that the role of frost in causing loss
      of hydraulic conduction by embolism is much more dramatic in Quercus than in
      conifers and diffuse porous hardwoods.

PMID- 14972932
TI  - Low humidity can cause uneven photosynthesis in olive (Olea europea L.) leaves.
AB  - We examined the photosynthetic responses of olive (Olea europea L.) leaves
      exposed to either (a) two hours of high leaf-to-air vapor pressure difference
      (vpd) or (b) four 30-min cycles of high vpd separated by 15-min periods of
      recovery at low vpd. Neither treatment affected photosynthesis when vpd was less
      than 3.0 kPa. Photosynthesis by mature leaves was also insensitive to higher vpd,
      but photosynthesis of young leaves was reduced by both treatments at a vpd higher
      than 3.2 kPa. This effect of vpd was much smaller under high intercellular CO(2)
      pressure. Autoradiograms showed that under a vpd of 3.2 kPa, mature leaves
      photosynthesized uniformly, but patches of reduced CO(2) fixation occurred in the
      distal part of young leaves. We conclude that heterogeneities in photosynthesis
      along the length of the leaf caused the apparent reduction of photosynthesis in
      our experiments. This pattern of patchy photosynthesis was different from that
      observed in mesophytic herbs, but the effect on gas exchange analysis was the
      same. In this case, apparent biochemical effects of low humidity on
      photosynthesis of young olive leaves are likely an artifact.

PMID- 14972933
TI  - A model of carbon storage in forests and forest products.
AB  - This paper discusses the general formulation of a model that describes carbon
      storage in a forest and its timber products as a function of the forest growth
      curve, the rotation period and the carbon retention curves for the timber
      products. After a number of rotations, the rotation-averaged quantity of stored
      carbon approaches an asymptotic value. It is shown that, when forests are managed
      for maximum sustained yield of biomass, the contribution to asymptotic carbon
      storage from timber products is about 2.5D/T* times the contribution from living
      trees, where D is the characteristic decay time for reconversion of timber
      products to carbon dioxide, and T* is the normal rotation period for maximum
      sustained yield. For a given value of D/T*, carbon storage can be optimized if
      the policy of maximizing sustained yield is relaxed. For D/T* < 1, as the
      rotation period is increased indefinitely, the asymptotic level of carbon storage
      increases monotonically toward the value of the carbon content of living trees at
      maturity, g(f). For D/T* > 1, there is a finite, optimal rotation period, T(o),
      greater than T*, for which asymptotic carbon storage is greater than g(f). As
      D/T* tends to large values, however, T(o) tends to T*, so that, in this limit,
      management for maximum sustained yield also ensures maximum carbon storage. From
      initial planting, the time taken to reach asymptotic carbon storage decreases as
      the normal rotation period, T*, decreases, but increases almost linearly with
      increasing decay time of timber products, D. This result qualifies the short-term
      value of any particular planting strategy.

PMID- 14972934
TI  - Bud dormancy in beech (Fagus sylvatica L.). Effect of chilling and photoperiod on
      dormancy release of beech seedlings.
AB  - Two-year-old Fagus sylvatica L. seedlings were subjected to natural winter
      chilling or were overwintered in a heated greenhouse. Plants were then grown in
      controlled environment chambers with photoperiods of 9 or 13 h. Renewal of bud
      growth was found to be mainly determined by winter chilling. There was a slight
      interaction between chilling and photoperiod. Sprouting of apical buds took two
      to three times as long in unchilled plants as in chilled plants. Shoot elongation
      was influenced by chilling and was also greater in the 13-h photoperiod than in
      the 9-h photoperiod, but this may have been due at least in part to the higher
      irradiance. Chilling resulted in rapid dormancy loss and changed the growth
      pattern from basitonal to acrotonal.

PMID- 14972935
TI  - Response of five temperate deciduous tree species to water stress.
AB  - Gas exchange, tissue water relations, and leaf/root dry weight ratios were
      compared among young, container-grown plants of five temperate-zone, deciduous
      tree species (Acer negundo L., Betula papyrifera Marsh, Malus baccata Borkh,
      Robinia pseudoacacia L., and Ulmus parvifolia Jacq.) under well-watered and water
      stressed conditions. There was a small decrease (mean reduction of 0.22 MPa
      across species) in the water potential at which turgor was lost (Psi(tlp)) in
      response to water stress. The Psi(tlp) for water-stressed plants was -1.18, 
      1.34, -1.61, -1.70, and -2.12 MPa for B. papyrifera, A. negundo, U. parvifolia,
      R. pseudoacacia, and M. baccata, respectively. Variation in Psi(tlp) resulted
      primarily from differences in tissue osmotic potential and not tissue elasticity.
      Rates of net photosynthesis declined in response to water stress. However,
      despite differences in Psi(tlp), there were no differences in net photosynthesis
      among water-stressed plants under the conditions of water stress imposed. In A.
      negundo and M. baccata, water use efficiency (net photosynthesis/transpiration)
      increased significantly in response to water stress. Comparisons among water
      stressed plants showed that water use efficiency for M. baccata was greater than
      for B. papyrifera or U. parvifolia. There were no significant differences in
      water use efficiency among B. papyrifera, U. parvifolia, A. negundo, and R.
      pseudoacacia. Under water-stressed conditions, leaf/root dry weight ratios (an
      index of transpiration to absorptive capacity) ranged from 0.77 in R.
      pseudoacacia to 1.05 in B. papyrifera.

PMID- 14972936
TI  - Localization of the porous partition responsible for pressurized gas transport in
      Alnus glutinosa (L.) Gaertn.
AB  - The pressurized gas transport which improves the oxygen supply of the roots of
      the wetland tree black alder (Alnus glutinosa (L.) Gaertn.), is based on the
      existence of a thermo-osmotically active porous tissue partition in the lower
      part of the trunk with pore diameters in the range of, or smaller than, the mean
      free path length of the gas molecules (e.g., 70 nm for O(2) at 20 degrees C and
      100 kPa). Anatomical studies have shown that only the cambial layer or the
      phellogen of the lenticels have intercellular spaces small enough to be
      responsible for thermo-osmotic activity. The final localization of the thermo
      osmotically active partition and the determination of the pore sizes were done by
      diffusion and effusion experiments with basal trunk pieces of 3- to 4-year-old
      trees. The mean pore sizes of the intercellular system were not smaller than 100
      nm in diameter in the cambial layer separating the bark from the wood, but 14 +/-
      7 nm in diameter in the phellogen underlying the lenticels. Because of these
      small pores, the phellogen of the lenticels is the significant thermo-osmotically
      active partition for the transport of air to the root system in black alder.

PMID- 14972937
TI  - Theoretical study of variables affecting the export of assimilates from branches
      of Picea.
AB  - A theoretical analysis was done to identify the features of conifer branch
      development, based on a model for Picea sitchensis (Bong.) Carr., that affect the
      ability to export assimilates, assuming (i) a branch's requirement for
      assimilates is determined by its need for mechanical support, and (ii) the
      production of assimilates is a simple function of total shoot length. There were
      three salient findings. First, there is an optimum and maximum shoot length for
      assimilate export by unbranched shoots. Second, the less a shoot extends itself
      each year, the more assimilate it may export, all else being equal. Third, there
      is a larger surplus of assimilates for export when a shoot develops laterals. A
      combination of lateral branching, deflection and decreased elongation can enable
      branches to continue growing and exporting assimilates for many years, as occurs
      at the bases of tree crowns.

PMID- 14972938
TI  - Seasonal changes in amino acids, protein and total nitrogen in needles of
      fertilized Scots pine trees.
AB  - Seasonal changes in amino acids, protein and total nitrogen in needles of 30-year
      old, fertilized Scots pine (Pinus sylvestris L.) trees growing in Northern Sweden
      were investigated over two years in field experiments. The studied plots had been
      fertilized annually for 17 years with (i) a high level of N, (ii) a medium level
      of N, or (iii) a medium level of N, P and K. Trees growing on unfertilized plots
      served as controls. In control trees, glutamine, glutamic acid, gamma
      aminobutyric acid, aspartic acid and proline represented 50-70% of the total free
      amino acids determined. Arginine was present only in low concentrations in
      control trees throughout the year, but it was usually the most abundant amino
      acid in fertilized trees. Glutamine concentrations were high during the spring
      and summer in both years of study, whereas proline concentrations were high in
      the spring but otherwise low throughout the year. In the first year of study,
      glutamic acid concentrations were high during the spring and summer, whereas
      gamma-aminobutyric acid was present in high concentrations during the winter
      months. This pattern was less pronounced in the second year of investigation. The
      concentrations of most amino acids, except glutamic acid, increased in response
      to fertilization. Nitrogen fertilization increased the foliar concentration of
      arginine from < 1 micromol g(dw) (-1) in control trees to a maximum of 110
      micromol g(dw) (-1). Trees fertilized with nitrogen, phosphorus and potassium had
      significantly lower arginine concentrations than trees fertilized with the same
      amount of nitrogen only. Protein concentrations were similar in all fertilized
      trees but higher than those in control trees. For all treatments, protein
      concentrations were high in winter and at a minimum in early spring. In summer,
      the protein concentration remained almost constant except for a temporary
      decrease which coincided with the expansion of new shoots. Apart from arginine,
      the amino acid composition of proteins was similar in all treatments.

PMID- 14972939
TI  - A method for reconstructing the development of the sapwood area of balsam fir.
AB  - Leaf area is commonly estimated as a function of sapwood area. However, because
      sapwood changes to heartwood over time, it has not previously been possible to
      reconstruct either the sapwood area or the leaf area of older trees into the
      past. In this study, we report a method for reconstructing the development of the
      sapwood area of dominant and codominant balsam fir (Abies balsamea (L.) Mill.).
      The technique is based on establishing a species-specific relationship between
      the number of annual growth rings in the sapwood area and tree age. Because the
      number of annual growth rings in the sapwood of balsam fir at a given age was
      found to be independent of site quality and stand density, the number of rings in
      sapwood (NRS) can be predicted from the age of a tree thus: NRS = 14.818 (1 - e(
      0.031 age)), unweighted R(2) = 0.80, and NRS = 2.490 (1 - e(-0.038 age)),
      unweighted R(2) = 0.64, for measurements at breast height and at the base of the
      live crown, respectively. These nonlinear asymptotic regression models based only
      on age, were not improved by adding other tree variables such as diameter at
      breast height, diameter at the base of the live crown, total tree height or
      percent live crown.

PMID- 14972940
TI  - Accumulation of free amino acids in the shoots and roots of three northern
      conifers during drought.
AB  - The effects of drought on the free amino acid pools in 21- to 23-week-old
      seedlings of black spruce (Picea mariana (Mill.) Britt.), white spruce (Picea
      glauca (Moench.) Voss) and jack pine (Pinus banksiana Lamb.) were followed during
      soil drying. Although water and pressure potentials were sensitive to water
      deficits, large changes in osmotic potential were not recorded until after the
      development of severe drought. Total soluble amino nitrogen in the shoots and
      roots of the three species rose as turgor declined, with peak concentrations
      attained late in the drought period when the pressure potentials of the shoots
      approached zero. All white spruce seedlings were alive at zero turgor and showed
      large decrements in osmotic potential, but concentrations of free amino nitrogen
      in the roots and shoots showed only modest increases, reaching 125 to 150% of
      their control values. In contrast, large numbers of black spruce and jack pine
      were dead or severely damaged at zero turgor, and only small changes in osmotic
      potential were detected during soil drying. Nevertheless, concentrations of
      soluble amino nitrogen in both species reached 150 to 200% of control values a
      few days before the seedlings died. Alanine, arginine, aspartic acid/asparagine,
      glutamic acid/glutamine, glycine, hydroxyproline and proline were the major
      components of the free amino acid pools under both water-stressed and non
      stressed conditions, with the largest and most consistent increases observed in
      the roots of all three conifers. Although proline was an important and dynamic
      component of the free pools, absolute concentrations were commony equalled or
      exceeded by other free amino acids in the roots and shoots and nearly always
      exceeded by the concentration of aspartic acid/asparagine in both tissues.
      Differences in drought resistance among the three conifers were not reflected by
      unique patterns of amino acid accumulation or by large differences in absolute
      concentrations of the free amino acid pools.

PMID- 14972941
TI  - Drought adaptations and responses in five genotypes of Fraxinus pennsylvanica
      Marsh.: photosynthesis, water relations and leaf morphology.
AB  - Genotypic variation in photosynthesis and plant water relations during drought,
      and in leaf and seedling morphology were examined in greenhouse-grown Fraxinus
      pennsylvanica Marsh. (green ash) from five populations located along an east-west
      transect from New York State to South Dakota. During a 17-day drought, South
      Dakota seedlings, from the most xeric habitat, maintained the highest net
      photosynthesis and leaf conductance, and New York seedlings, from the most mesic
      habitat, exhibited the lowest net photosynthesis and leaf conductance. All
      populations except New York adjusted osmotically during the 17-day drought, by
      the end of which New York seedlings had the highest osmotic potentials at full
      and zero turgor. Tissue elasticity increased in New York seedlings, but decreased
      in Nebraska seedlings during the drought. Leaves of South Dakota seedlings were
      the most xerophytic. They were smaller in area and greater in thickness and
      specific mass than leaves of other sources. Leaves of New York seedlings were
      thinner than those of the other genotypes and among the largest. Seedlings from
      South Dakota were smaller than those of the other populations.

PMID- 14972942
TI  - Selection and physiology of cell cultures of Douglas-fir grown under conditions
      of water stress.
AB  - Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) cell cultures sampled 3, 6, or
      9 days after subculture in nutrient medium were able to survive subsequent
      subculture in a medium containing 15% polyethylene glycol (PEG) (M(r) 6000-8000)
      (-1.21 MPa), whereas cell sampled 12 or 16 days after subculture in nutrient
      medium became senescent when transferred to a medium containing 15% PEG. Cells
      sampled after subculture for 3, 6, or 9 days in nutrient medium had lower fresh
      weight/dry weight ratios, lower osmotic potentials, smaller cell diameters, and
      higher turgor pressures than cells sampled after 12 or 16 days subculture in
      nutrient medium. Cells surviving subculture to a medium containing 15% PEG did
      not increase in dry weight for 5 weeks even though the medium was exchanged every
      7 days. After 5 weeks, however, dry weight growth resumed and reached 75% of the
      level attained by control cells grown on PEG-free medium. Long-term growth on a
      medium containing 15% PEG (PEG-selected cells) could only be sustained if the
      medium was supplemented with 30 mM glutamine. The PEG-selected cells grew in
      small clusters, were isodiametric, and had chlorophyll contents 50% higher than
      unselected cells. The PEG-selected cells also showed lowered cellular osmotic
      potentials, presumably due to osmoregulation. Turgor pressures of PEG-selected
      cells were greater than or equal to those of unselected cells.

PMID- 14972943
TI  - Energy costs of flowering, fruiting, and cherelle wilt in cacao.
AB  - Groups of 14-year-old cacao (Theobroma cacao L.) trees were hand pollinated,
      pollinated naturally or had their fruits continuously removed. Wilted and non
      wilted cherelles (small fruits) were counted every 2 weeks, fallen flowers were
      counted weekly and mature pods were harvested monthly from 1983 through 1986.
      Carbohydrate, lipid and protein contents of wilted cherelles, mature pods and
      flowers were determined. Continuous removal of fruits caused a constant
      initiation of flowers and a significant increase in flowering intensity compared
      with the other treatments. The quantity of cherelles in the hand-pollinated trees
      was significantly greater than in the naturally pollinated trees. However, the
      number of mature fruits in both treatments was not statistically different
      because of increased cherelle wilting in the hand-pollinated trees. The
      continuously depodded trees allocated approximately 8 and 5 times more assimilate
      to flower production than the hand- and naturally pollinated trees, respectively.
      The naturally pollinated trees used only about one third as much energy for the
      production of flowers and wilted cherelles as the hand-pollinated trees, but
      about 1.4 times more energy than the depodded trees. It is concluded that fruit
      set in cacao is regulated by assimilate production and that cherelle wilting is
      the mechanism whereby the tree adjusts production.

PMID- 14972944
TI  - Solution aluminum and transpiration in Picea rubens and Gleditsia triacanthos
      seedlings.
AB  - Soil solution Al may contribute to red spruce (Picea rubens Sarg.) decline by
      inhibiting transpiration (Klein 1985). This study examines how Al affects
      transpiration in red spruce and honeylocust (Gleditsia triacanthos L.) seedlings
      and explores mechanisms for the observed responses. Red spruce seedlings were
      grown in dilute nutrient solutions containing 0 to 925 microM Al at pH 4.5 or
      3.8. Solution Al had no effect on the transpiration, root hydraulic conductivity
      (K(r)) or shoot water potential (Psi) of red spruce. Transpiration of honeylocust
      was higher in the presence of 100 to 350 microM Al than 0, 500, or 600 microM Al.
      The Al-induced increases in transpiration of honeylocust were unrelated to shoot
      Psi or root K(r), but were closely correlated with the greater root lengths
      produced by intermediate levels of Al. In neither species was transpiration
      correlated with tissue concentrations of Al, P, K, Ca or Mg.

PMID- 14972945
TI  - Analysis of the morphology and structure of crowns in a young sugi (Cryptomeria
      japonica) stand.
AB  - Crown form, vertical changes in branch inclination and vertical distribution of
      foliage density in a young sugi (Crytomeria japonica D. Don) stand were analyzed
      using allometric equations. Tall trees had deeper crowns than short trees,
      whereas the crown diameters of both tall and short trees were similar. Apical
      roundness was more pronounced in the lower-story trees, which were characterized
      by umbrella-shaped crowns. The vertical distribution of foliage density was
      approximated by a nearly symmetrical curve. Tall trees had higher spatial
      densities of foliage than short trees. Branch inclination also varied
      significantly with tree height. The middle-story trees had the largest branch
      inclinations and the lower-story trees had the smallest branch inclinations. Even
      in young uniform stands, crown morphology and structure were modified in response
      to the light environment.

PMID- 14972946
TI  - Shoot structure, leaf area index and productivity of evergreen conifer stands.
AB  - For 12 conifer species, the maximum ratio of shoot to leaf silhouette area of
      shade-acclimated shoots was found to vary from 0.50 to 0.99. Maximum leaf area
      index (leaf area per unit ground area) of conifer stands varied from 3.5 to 20,
      and maximum mean annual increment varied by a factor of 2. Significant
      correlations were found between leaf silhouette area ratio of shade-acclimated
      shoots and the maximum leaf area index (R(2) = 0.84) and the maximum mean annual
      increment (R(2) = 0.93). These results support a hypothesis that species to
      species differences in the morphology of shade-adapted shoots strongly affect
      both the development of leaf area and the productivity of stands of evergreen
      conifers.

PMID- 14972947
TI  - Influence of female cones on the vegetative growth of Pinus contorta trees.
AB  - Branches of Pinus contorta Dougl. bearing two-year-old female cones initiated
      fewer lateral buds than vegetative branches. However, the number of lateral
      shoots that differentiated and grew was not reduced on female cone-bearing
      branches. Neither the number nor the weight of female cones influenced the length
      of the terminal shoot. The total length of all lateral shoots was positively
      associated with the weight of two-year-old female cones. Branch units with two
      year-old female cones produced significantly more total dry weight in the current
      year than vegetative branch units. There was, however, no significant reduction
      in the dry weight of terminal and lateral shoots. Branches bearing female cones
      allocated between 17 and 45% of the current year's dry weight to two-year-old
      cones and between 1 and 5% was allocated to one-year-old female cones. Female
      cones therefore apparently do not reduce the photosynthetic potential of trees.
      The influence of female cones compared with male cones on the growth of trees is
      discussed.

PMID- 14972948
TI  - Effects of aluminum on growth and nutrient status of Douglas-fir seedlings grown
      in culture solution.
AB  - Effects of Al on growth, nutrient uptake and proton efflux were studied in
      Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) seedlings grown for about nine
      months in culture solutions with a pH between 3.4 and 3.6 and with both calcium
      and magnesium (Ca + Mg) at a concentration of 0.1, 0.5 or 2.5 mM. In the absence
      of Al, plant dry matter production and root development increased with increasing
      concentrations of (Ca + Mg) in the culture solution. At the low and intermediate
      (Ca + Mg) concentrations, optimal root and shoot development were observed at an
      Al concentration of 4 mg l(-1). At the highest (Ca + Mg) concentration, Al up to
      4 mg l(-1) did not affect growth, but at higher concentrations, it significantly
      reduced both shoot and root growth. As the concentration of (Ca + Mg) in the
      nutrient solution increased, the concentrations of Ca and Mg increased in shoots
      and roots also. The concentrations of Ca and Mg in the roots were unaffected by
      the presence of Al, whereas in the shoots they were either unaffected, or
      increased, by Al. Concentrations of Al in, or on, roots, or in shoots, did not
      change in response to changing concentrations of Ca + Mg in the nutrient medium.
      In general, concentrations of P and K in shoots and roots were higher in
      seedlings grown in nutrient solutions containing Al. Stimulation of growth by
      moderate concentrations of Al, which was observed at suboptimal (Ca + Mg)
      concentrations, was associated with a low NH(4) preference and a low root proton
      efflux. The Al-induced increase in internal K concentration and reduction in
      NH(4) preference may be explained by a lower efflux of K and NO(3), respectively.

PMID- 14972949
TI  - Induction of acropetal (14)C-photosynthate transport and radial growth by indole
      3-acetic acid in Pinus sylvestris shoots.
AB  - The relationship between radial growth and assimilate movement was determined in
      one-year-old Pinus sylvestris (L.) cuttings collected during the dormant period
      and reactivated for 1-27 days under environmental conditions favorable for
      growth. The cuttings were either left with buds intact, defoliated along the
      distal 8 cm, or debudded and treated apically with 0 or 1 mg g(-1) indole-3
      acetic acid (IAA) in lanolin. Radial growth was measured as tracheid production
      and bark radial width. The distribution of (14)C-photosynthate 1 or 5 days after
      exposure to (14)CO(2) was used to indicate assimilate movement. Debudding
      inhibited tracheid production and decreased acropetal (14)C-photosynthate
      transport, whereas applying IAA to debudded cuttings promoted both these
      processes and, in addition, induced vigorous callus growth within the bark
      immediately below the application point. Distal defoliation markedly increased
      the amount of (14)C-photosynthate transported toward the apex without altering
      how debudding and exogenous IAA affected tracheid production and the distribution
      of (14)C-photosynthate. The production of tracheids induced by apically applied
      IAA in debudded and distally defoliated cuttings increased progressively in
      material collected on September 9, October 14 and November 24, whereas bark
      radial width and acropetal (14)C-photosynthate movement increased only between
      the first two collection dates. Ringing midway between the IAA source and the
      bottom of the distally defoliated region with a lanolin mixture of 10 mg g(-1)N-1
      naphthylphthalamic acid (NPA), 1 mg g(-1) methyl-2-chloro-9-hydroxy-fluorene-9
      carboxylic acid (CF) or 10 mg g(-1) phenylacetic acid (PAA) reduced radial growth
      and [1-(14)C]IAA transport below the ring and locally promoted radial growth and
      accumulated radioactivity above. (14)C-Photosynthate transport into the region
      above the ring either was not altered (CF, PAA) or was increased (NPA). The
      results indicate that apically applied IAA induces the acropetal movement of
      (14)C-photosynthate in debudded P. sylvestris shoots by locally promoting
      activity correlated with tracheid and callus production rather than by affecting
      radial growth or phloem transport processes, or both, at a distance below the IAA
      source.

PMID- 14972950
TI  - Variations in amounts of carbohydrates, amino acids and adenine nucleotides in
      mulberry tree (Morus alba L.) stems during transitional phases of growth.
AB  - Quantitative changes in carbohydrates, amino acids and adenine nucleotides in the
      stems of mulberry trees (Morus alba L., cv. Shin-ichinose) were followed from
      spring to early summer and from autumn to early spring. Both ATP and ADP content
      of stems increased before bud break, whereas the content of sucrose, the most
      abundant sugar among the stem carbohydrates, decreased. The sucrose content fell
      to its lowest value at the beginning of May, and then increased rapidly, whereas
      the starch content decreased suggesting consumption of reserve carbohydrate and
      simultaneous accumulation of current photosynthate. This was confirmed by studies
      in which reserve carbohydrates were labeled with (14)CO(2). Proline content of
      stems increased from the time of leaf shedding until early spring. Although it
      was the most abundant amino acid at the time of bud break, proline rapidly
      decreased as new shoots developed and was hardly detectable by the beginning of
      May. The asparagine and arginine contents increased transiently following bud
      break, and then decreased toward summer. Transient increases in glutamine and
      arginine were noted at the time of leaf shedding.

PMID- 14972951
TI  - Integration of sapflow velocity to estimate plant water use.
AB  - The heat pulse technique provides an estimate of sapflow velocity at one position
      within the xylem of an individual plant. Previous experience has shown that the
      velocity profile across the conducting area cannot be assumed to be constant,
      necessitating several such point estimates for a reasonable characterization of
      the velocity profile with depth. These point estimates must be integrated over
      the sapwood conducting area to derive flux. The most common method is to fit a
      one degree of freedom least-squares polynomial to the point estimates, and then
      to integrate this equation across the sapwood profile and around the bole. An
      alternative method is presented based on a weighted average approach. The latter
      is shown to be a more robust estimator of flux when velocity profiles exhibit
      large curvatures.

PMID- 14972952
TI  - Cellular basis for limitation of poplar leaf growth by water deficit.
AB  - During the summers of 1986 and 1987, stem and leaf growth were measured on
      coppiced plants of Populus trichocarpa Torr. & A. Gray, P. deltoides Bartr. ex
      Marsh, and P. trichocarpa x deltoides growing in the field in Puyallup, WA. The
      trees were either irrigated periodically throughout the season, or grown without
      irrigation. In both treatments, stem volume at the end of the growing season was
      directly proportional to total leaf area in all three genotypes. The rate of
      individual leaf growth was reduced by lack of irrigation more in the parental
      species than in the hybrid. Only in the parental species did unirrigated trees
      have lower leaf water potentials (predawn and midday) than irrigated trees.
      However, stomatal conductances of all three genotypes were lower in unirrigated
      trees than in irrigated trees. Osmotic potentials of growing leaves of all three
      genotypes were also lower in unirrigated trees than in irrigated trees. As a
      consequence, turgor of growing leaves was as great in unirrigated trees as in
      irrigated trees, which indicates that turgor differences cannot explain the lower
      rates of leaf growth in the unirrigated trees. However, cell wall extensibility
      of leaves was lower in unirrigated trees than in irrigated trees, and the
      difference was greater in the parental species than in the hybrid. Unlike its
      effect on leaf area growth, irrigation increased stem volume growth of the hybrid
      and the parental species by a similar amount (12-16%).

PMID- 14972953
TI  - Leaf growth of Eucalyptus globulus seedlings under water deficit.
AB  - Eucalyptus globulus Labill. seedlings grown under field conditions in Portugal
      were watered either daily (control) or every 6 days (drought-treated). Relative
      to those of control plants, rates of leaf production and leaf biomass
      accumulation were reduced by almost half in drought-treated plants. However,
      whereas expansion of new leaves on control plants slowed toward the end of the 30
      day experiment, expansion of leaves of the same age on drought-treated plants
      accelerated as a change in weather conditions resulted in midday plant water
      potentials above -3.0 MPa. In plants that were left unwatered until they wilted
      and were then watered daily, expansion of the fifth leaf pair from the apex was
      slower than that of the same pair of leaves of plants watered daily throughout;
      but it continued for about twice as long and resulted in the same final leaf
      area. Drought treatment also caused a substantial reduction in the rate of leaf
      production, which, in part, accounted for the effect of drought on leaf biomass
      production. In a greenhouse study, witholding water for 15 days had only a slight
      effect on the length or width of adaxial epidermal cells, and the effect was
      quickly reversed on rewatering.

PMID- 14972954
TI  - Autotetraploid plants from callus cultures of Betula pendula Roth.
AB  - Autotetraploid plants with 2n = 56 chromosomes were found in a population of
      plants derived from callus cultures of stem internodes of silver birch (Betula
      pendula Roth) with 2n = 28 chromosomes. These plants were readily identified by
      their twisted, pubescent foliage and slow rate of growth, and by cytological
      examination. The frequency of autotetraploidy varied with the auxin used in the
      culture medium. When indole-3-butyric acid was used, autotetraploids accounted
      for 3.8% of the total study population, whereas when naphthaleneacetic acid was
      used, the frequency of autotetraploidy increased to 11.0%. The remainder of the
      plants in the study population were morphologically normal with 2n = 28
      chromosomes. The autotetraploids have potential value as breeding material for
      the production of triploid birches (2n = 42), which are known to be fast growing,
      through crosses with diploid silver birch.

PMID- 14972955
TI  - Differential responses persist in shoot explants regenerated from callus of two
      mature black locust trees.
AB  - Callus cultures were established from internodal segments of shoot cultures from
      two mature black locust Robinia pseudoacacia L. trees. Callus of both trees
      produced shoots on Murashige and Skoog (MS) medium supplemented with 10 microM 6
      benzylaminopurine alone or in combination with 1 microM naphthaleneacetic acid.
      Regenerated shoots were successfully multiplied on MS medium containing 0.32
      microM 6-benzylaminopurine, and produced roots on 0.1 strength MS medium
      containing 1 microM indole-3-butyric acid. One clone consistently outperformed
      the other with respect to shoot proliferation and proportion of shoots that
      produced roots. This distinction had previously been observed in shoots produced
      from bud explants obtained from the mature trees.

PMID- 14972956
TI  - Influence of cold hardening on water relations of three Eucalyptus species.
AB  - Water relations of three Eucalyptus species (E. x trabutii Wilm., E. viminalis
      Labill., E. dalrympleana Maid.), widely planted in the Mediterranean basin, were
      analyzed throughout an entire year in relation to natural cold hardening. Osmotic
      potential, both at saturation and at the turgor loss point, showed a greater
      reduction during hardening in the more frost-resistant E. viminalis and E.
      dalrympleana than in the more frost-sensitive E. x trabutii. The hardening
      capabilities of all species were analyzed in relation to the freezing dehydration
      index, FDI, a parameter derived from pressure-volume analysis which represents
      the water lost when cells, initially at the turgor loss point, attain
      thermodynamic equilibrium with extraplasmatic ice. The FDI at the killing
      temperature showed little variation either between frost-sensitive and frost
      resistant species, or between hardened and non-hardened plants. The index may,
      therefore, be useful for evaluating a plant's potential for injury by freeze
      induced desiccation.

PMID- 14972957
TI  - Photosynthesis patterns during the establishment year within two Populus clones
      with contrasting morphology and phenology.
AB  - Diurnal and seasonal photosynthesis patterns were studied in poplar clones
      Populus tristis Fisch. x P. balsamfera L. cv. Tristis #1 (NC 5260) and Populus x
      euramericana (Dode) Guiner cv. Eugenei (NC 5326, Carolina poplar) during their
      first season in the field in a short rotation, intensive culture plantation.
      Photosynthetic rates were low in immature leaves; increased basipetally on the
      shoot and peaked in leaves that had recently reached full expansion; and
      thereafter declined in lower-crown leaves in both clones. Photosynthesis was
      associated with leaf age and stomatal conductance in immature leaves; adaxial
      photosynthetic photon flux density (PPFD) and leaf temperature in recently mature
      leaves; and leaf age and adaxial PPFD in lower-crown leaves. Diurnal
      photosynthesis patterns within trees were highly variable due to differential
      light interception among leaves. Results of clonal comparisons of photosynthetic
      rates were dependent on which leaves were pooled for comparison and how
      photosynthesis was expressed. Compared to Eugenei, Tristis produced smaller
      leaves which had higher unit-area photosynthesis rates. The more indeterminate
      Eugenei outgrew Tristis principally because it more fully utilized the growing
      season for leaf area production. Photosynthetic production integrated over the
      growing season was closely related to dry matter production in both clones.

PMID- 14972958
TI  - Timing of growth cessation in relation to climatic adaptation of northern woody
      plants.
AB  - The efficiency of timing models of cessation of growth of northern woody plants
      was defined as their ability to allow maximum utilization of the growing season
      without autumn frost damage. The efficiencies of three timing models were
      compared with the aid of computer simulations, using long-term meteorological
      data. A model based on night length was the most efficient, followed by one based
      on a joint factor of the night length and temperature sum. A model based on
      temperature sum alone was the least efficient. The reason for these differences
      in efficiency was the great year-to-year variation in the annual temperature sum
      accumulation. The results were compared with empirical evidence for each of the
      models. The relevance of the theoretical approach is discussed, as well as the
      application of the simulations.

PMID- 14972959
TI  - Needle growth in Sitka spruce (Picea sitchensis): effects of nutrient deficiency
      and needle position within shoots.
AB  - Needle development and shoot growth were studied in 14- and 20-year-old Sitka
      spruce (Picea sitchensis (Bong.) Carr.) planted on an oligotrophic peat and
      fertilized with N, P and K (control), N and P (-K), N and K (-P) or unfertilized
      (-NPK). Shoot extension, needle number, and the size and number of needle cells
      were observed throughout the season. Beginning with bud burst in early May,
      needle growth continued for nine weeks in the control treatment. Needle growth in
      the mineral deficiency treatments terminated at the same time as in the controls,
      although it did not begin until up to three weeks later than in the control
      trees. Needles developed acropetally along the shoot, with basal needles
      completing their development first. Cell division in needles of control trees
      lasted about 3 weeks, with cell expansion continuing for a further 3 weeks.
      Initial mean cell cycle times were shortest for proximal needles following bud
      burst, but lengthened as the season progressed. Cell number increased from 6600
      in the primordia to 200 000 in mature needles. Final needle dimensions and cell
      number varied according to the position of the needle on the shoot. The largest
      needles with the most cells were near the middle of the shoot. Relative to the
      controls, all mineral deficiency treatments reduced shoot length, bud and needle
      dimensions, and needle cell number, particularly the -P treatment. Potassium and
      P deficiency treatments reduced primordial cell number by up to 42%, whereas
      final mean cell size was 30% greater in the -P treatment, 17% greater in the -NPK
      treatment, but 14% smaller in the -K treatment. Mean cell size was constant for
      needles at all positions in any particular treatment at any time, so that final
      needle size was determined by cell number alone. Needle dry weight/fresh weight
      ratio continued to increase until early August, with significantly higher ratios
      in the -K and -P treatments than in the controls.

PMID- 14972960
TI  - Water movement in yellow-cedar seedlings and rooted cuttings: comparison of whole
      plant and root system pressurization methods.
AB  - One-year-old yellow-cedar (Chamaecyparis nootkatensis (D. Don) Spach) seedlings
      and rooted cuttings were taken from cold-storage facilities and grown in aerated
      water in a controlled environment room for 21 days. Root areas of seedlings and
      rooted cuttings were initially comparable, but after 21 days seedlings had
      produced more than twice as much new root area as rooted cuttings. Water flow
      resistance through the plant-atmosphere continuum decreased in both stock types
      over the 21-day period. In both seedlings and rooted cuttings, transpirational
      flux density increased in a curvilinear manner as new root area increased. Root
      resistance to water movement decreased sharply with increasing new root area up
      to 20 cm(2) in both seedlings and rooted cuttings. Further increases in new root
      area did not result in further changes in root resistance of either stocktype.
      Plant water movement was measured by both the whole plant and the root system
      pressurization methods with results differing between the two techniques.

PMID- 14972961
TI  - Influence of water stress on the physiology and growth of red spruce seedlings.
AB  - Two-year-old, container-grown red spruce (Picea rubens Sarg.) seedlings from a
      New Hampshire seed source were exposed to 10 or 11 drying cycles in which the
      seedlings were not watered until their midday (1400 h) xylem water potentials
      averaged -1.57 MPa. Control seedlings were kept well watered to maintain midday
      water potentials of about -0.73 MPa. After the final drying cycle, the water
      stressed seedlings were rehydrated and osmotic potentials were determined by
      pressure-volume analysis. Gas exchange at ambient CO(2) concentration (338 ppm)
      and at an elevated CO(2) concentration (838 ppm) was measured on both groups of
      plants as they slowly dried down. No osmotic adjustment or photosynthetic
      acclimation occurred as a result of the water-stress treatment and both groups of
      seedlings maintained photosynthesis to water potentials as low as -3.0 MPa.
      Twenty-four hours after rehydration, the water-stressed seedlings had
      photosynthetic rates as high as the control seedlings. Estimated stomatal
      limitation to photosynthesis was approximately 30% down to water potentials of 
      1.4 MPa, but increased steadily as water potentials decreased further. At ambient
      CO(2) concentrations (338 ppm) and water potentials averaging -2.45 MPa,
      photosynthetic rates of water-stressed seedlings were 15% those of well-watered
      seedlings, whereas when the same water-stressed seedlings were measured in the
      presence of an elevated concentration of CO(2) (838 ppm) their photosynthetic
      rates were 73% those of well-watered seedlings measured at an ambient CO(2)
      concentration (338 ppm).

PMID- 14972962
TI  - Abscisic acid and the regulation of embryo dormancy in the genus Acer.
AB  - Germination of Acer pseudoplatanus L. and Acer platanoides L. seeds was increased
      by moist storage of the intact fruits (seed + pericarp) at 5 degrees C, but not
      at 17 degrees C. In both species, germinative capacity of isolated embryos (seeds
      with testa removed) was increased by moist storage of fruits at either 5 or 17
      degrees C. Thus dormancy loss by intact seeds and excised embryos was not
      necessarily correlated. Loss of dormancy in isolated embryos was associated with
      a reduction in free abscisic acid (ABA) content. Embryos from freshly harvested
      fruits of A. pseudoplatanus had a higher germinative capacity and a lower free
      ABA content than embryos from freshly harvested fruits of A. platanoides.
      Morever, germinative capacity increased, and free ABA content decreased, more
      rapidly with length of fruit storage in A. platanoides embryos than in A.
      pseudoplatanus embryos.

PMID- 14972963
TI  - Influence of explant source on in vitro axillary shoot formation in oak
      seedlings.
AB  - In vitro shoot development was slower for apical shoot explants of young oak
      (Quercus robur L.) seedlings growing on Woody Plant Medium containing activated
      charcoal than for nodal shoot explants. The rate of in vitro shoot development
      was slowest in explants taken from seedlings that were undergoing rapid shoot
      elongation and most rapid in explants taken from seedlings that had stopped
      elongating and had fully expanded leaves. Maximum rooting was achieved on half
      strength Woody Plant Medium containing activated charcoal. Rooting ability was
      not influenced by explant source.

PMID- 14972964
TI  - Ozone, acidic rain and soil magnesium effects on growth and foliar pigments of
      Pinus taeda L.
AB  - Height and diameter growth, biomass accumulation and leaf pigment concentrations
      were measured in loblolly pine (Pinus taeda L.) seedlings grown in soil
      containing 12 or 35 microg Mg g(-1) and exposed from May to October to
      subambient, ambient, or twice-ambient ozone (O(3)), and to simulated acidic rain
      with a pH of either 4.0 or 5.3. At the end of one growing season, height and
      diameter growth of seedlings exposed to twice-ambient O(3) were not statistically
      different from those of seedlings exposed to subambient O(3). Biomass of all
      plant parts was reduced by 7 to 16% in response to increasing O(3) concentration.
      No statistically significant growth responses to rain chemistry or soil magnesium
      status were observed, and there were no statistically significant interactive
      treatment effects. Needle pigment concentrations were not significantly affected
      by rain chemistry or soil Mg status and there were no visible signs of injury to
      needles that could be attributed to O(3) stress or Mg deficiency. Concentrations
      of chlorophyll a and b, and carotenes were 23, 30 and 21% higher (P </= 0.05)
      respectively, in seedlings exposed to twice-ambient O(3) than in seedlings from
      the other ozone treatments. There were no interactive treatment effects on needle
      pigment concentrations.

PMID- 14972965
TI  - Influence of male cones on early season vegetative growth of Pinus contorta
      trees.
AB  - On average, branches of Pinus contorta Dougl. bearing male cones had 35 fewer
      needle pairs than equivalent vegetative branches, and significantly fewer
      differentiated primordia (i.e., male cones + needle pairs + sterile cataphylls).
      It was estimated that the formation of male cones results in a 27-50% reduction
      in the number of needles per male cone-bearing branch. In early spring, branches
      bearing male cones had on average 23% (0.44 g) more dry weight than vegetative
      branches. On average, 95% of the dry weight of male cone-bearing branches was
      allocated to the terminal shoot (54% of which was male cones) and 5% to the
      lateral shoots. By comparison, vegetative branches allocated 85% of their total
      dry weight to the terminal shoot and 15% to the lateral shoots. These findings
      suggest that male cones may reduce the photosynthetic potential of the trees
      which bear them.

PMID- 14972966
TI  - An experimental test of a nitrogen uptake and partitioning model for young trees.
AB  - Simulation models of nitrate uptake and total nitrogen partitioning during the
      exponential growth phase of one-year-old peach trees (Prunus persica (L.)
      Batsch.) were tested in an experiment with 88 plants grown in soil-filled
      containers. Plants were fertilized with (15)N-NO(3) (-) and nitrate uptake
      estimated by periodic destructive analysis of plants for excess (15)N.
      Partitioning of N within the trees was followed by the analysis of plant parts
      for total N and (15)N. The nitrate uptake model, which provides one of the main
      inputs to the partitioning model, is based on a simplified form of the Michaelis
      Menten equation adapted to describe uptake by roots growing in soil layers. The
      nitrogen partitioning model considers each plant part (e.g., roots, trunk,
      shoots, leaves) as either a sink or a source for nitrogen. The model uses a flow
      equation, which is the same for all plant parts, to model the dynamics of
      nitrogen partitioning in the tree using increases in dry matter of various plant
      parts as driving force variables. The experiment demonstrated an error in the
      compartment organization of the partitioning model as a result of which the model
      failed to simulate changes in root N. A modification of the partitioning model
      structure to take account of the importance of trunk nitrogen reserves for root
      growth at the beginning of the growing season, which was indicated by the (15)N
      data, greatly improved prediction of root N. This modification is discussed in
      relation to the modeling approach.

PMID- 14972967
TI  - Seasonal variation in the photosynthetic capacity of a willow (Salix cv. Aquatica
      gigantea) canopy. 1 Changes in the activity and amount of ribulose 1,5
      bisphosphate carboxylase-oxygenase and the content of nitrogen and chlorophyll at
      different levels in the canopy.
AB  - The role of ribulose 1,5-bisphosphate carboxylase-oxygenase (Rubisco) in the
      regulation of photosynthesis in the field was assessed by following changes in
      the amount and activity of Rubisco and in the amounts of chlorophyll and total
      nitrogen in a willow (Salix cv. Aquatica gigantea) canopy during two growing
      seasons. An additional aim of this study was to determine how nitrogen is
      partitioned in the canopy and whether Rubisco and chlorophyll serve as sources of
      nitrogen. During both growing seasons, the total activity and the amount of
      Rubisco were high in young, sun-exposed leaves and decreased as the leaves aged
      and became shaded. In 1985, the specific activity was low (on average 0.8
      micromol mm(-1) mg(-1) Rubisco protein) compared with the values obtained in 1986
      (on average 1.8 micromol min(-1) mg(-1) Rubisco protein). These differences in
      the specific activity of Rubisco between the two years might be associated with
      changes in partitioning of nitrogen. During the cool summer of 1985, about 20% of
      the total nitrogen was partitioned to Rubisco compared with about 13% during the
      warm summer of 1986. Rubisco comprised a high proportion (about 60%) of the total
      soluble protein throughout the 1985 growing season, whereas during the 1986
      growing season, the proportion of Rubisco in the total soluble protein fraction
      was lower and decreased markedly as the leaves became shaded. Chlorophyll did not
      serve as a source of nitrogen in the canopy. On the contrary, the proportion of
      total nitrogen in chlorophyll increased with time, which indicates acclimation of
      the thylakoid membranes to decreasing irradiance. The degree of activation of
      Rubisco in samples collected in 1986 was high in young, sun-exposed leaves, which
      suggests that in these leaves, Rubisco may limit the rate of CO(2) uptake. In the
      shaded leaves of the lower canopy, the degree of activation of Rubisco was low,
      which indicates that in these leaves, photosynthesis is limited by factors other
      than Rubisco.

PMID- 14972968
TI  - Seasonal variation in the photosynthetic capacity of a willow (Salix cv. Aquatica
      gigantea) canopy. 2 Comparison of the structure and function of chloroplasts at
      different levels in the canopy.
AB  - Development of leaf chloroplast ultrastructure at five levels in a willow (Salix
      cv. Aquatica gigantea) canopy was followed during one growing season in the
      field. Changes in chloroplast ultrastructure were compared with the rate of CO(2)
      uptake of the same leaves. The highest rates of CO(2) uptake were recorded in
      young leaves exposed to full available sunlight. In these leaves, the area of the
      grana stacks was less than 20% of the total chloroplast area and the degree of
      thylakoid stacking was less than 1.5. The chloroplasts of these leaves contained
      large amounts of starch and small amounts of plastoglobuli. As the canopy grew
      and the leaves in the lower parts of the canopy became shaded, the structure of
      the chloroplast thylakoids gradually changed. In leaves at the two lowest levels
      of the canopy, the degree of stacking at the end of the growing season was close
      to 2 and correspondingly the rate of CO(2) uptake was low. The areas of grana
      stacks and plastoglobuli in these chloroplasts increased and were about 30 and
      10% of the chloroplast area, respectively, by the end of the growing season. The
      increase in the degree of thylakoid stacking was caused by increased biosynthesis
      of grana lamellae, which in general were thinner than the lamellae of young
      leaves. The length of the stroma lamellae did not change with leaf age.
      Morphometric measurements showed that the structure of the chloroplasts in leaves
      160 cm above ground was dynamic and responsive to environmental conditions so
      that photosynthetic capacity remained high for 7 weeks despite an increase in
      leaf shading.

PMID- 14972969
TI  - Water and nutrient supply regimes and the water relations of juvenile leaves of
      Eucalyptus globulus.
AB  - Pressure-volume analysis was used to study effects of irrigation and
      fertilization on the water relations of newly expanded juvenile leaves of
      Eucalyptus globulus Labill. seedlings growing in Portugal's Atlantic region. In
      May, at the beginning of the dry season, fertilization and irrigation treatments
      had no significant effects on the water relations parameters investigated. In
      September, at the end of the dry season, leaves from non-irrigated plants had a
      significantly higher apoplasmic water content and a higher dry weight/turgid
      weight ratio than leaves of similar physiological age from irrigated trees. The
      osmotic potential at full turgor and the water potential at the wilting point
      were lower in non-irrigated than in irrigated plants. Changes in osmotic
      potential at full turgor were negatively correlated with changes in dry
      weight/turgid weight ratio, suggesting that reductions in osmotic potential at
      full turgor were largely the result of decreases in cell size. Fertilization had
      no detectable effect on these variables or on leaf tissue bulk modulus of
      elasticity. Tissue elasticity was also unaffected by irrigation. Independently of
      water and nutrient supplies, leaf elasticity was higher and relative water
      content at the wilting point lower in leaves sampled in May than in leaves
      sampled in September. In non-irrigated plants, leaves sampled in September had a
      lower tissue elasticity and a lower osmotic potential at full turgor than leaves
      sampled in May, indicating that leaves produced at the end of the dry season
      generate lower water potentials as turgor is lost than leaves expanded early in
      the season.

PMID- 14972970
TI  - Adventitious roots, leaf abscission and nutrient status of flooded Gmelina and
      Tectona seedlings.
AB  - When flooded, seedlings of Gmelina arborea Roxb. produced more adventitious
      roots, had lower foliar Mn concentrations and lost fewer leaves than seedlings of
      Tectona grandis L.f. Severing the adventitious roots produced by flooded Gmelina
      seedlings increased leaf Mn concentration and leaf abscission and reduced whole
      plant dry matter production. Flooded Gmelina cuttings, which do not produce
      adventitious roots, abscised few leaves until foliar concentrations of Mn and Fe
      had risen substantially above those of unflooded cuttings, at which time most
      leaves were shed. The results indicate that the development of adventitious roots
      in flooded seedlings of Gmelina suppressed uptake of Mn thereby minimizing leaf
      abscission.

PMID- 14972971
TI  - Mineral nutrients, carbohydrates and phenolic compounds in leaves of beech (Fagus
      sylvatica L.) in southern Sweden as related to environmental factors.
AB  - Concentrations of major elements, trace elements, starch, total sugars and
      phenols were measured in leaves of beech (Fagus sylvatica L.) trees located at 89
      sites in the province of Scania, southern Sweden. Concentrations of elements had
      only a weak relationship to soil variables, but leaf N increased with distance
      from sources of industrial air pollution. Within-site variation in concentrations
      of most elements was smaller than variation among sites and was lowest for N, P,
      K and Cu and highest for Mn. Most trees had optimal or superoptimal
      concentrations of leaf N, whereas leaf concentrations of K, Mg and P were near or
      below the concentrations needed for normal growth. Several nutrients were
      negatively correlated with leaf color, total sugars and phenols, whereas insect
      damage was not related to any of the measured parameters.

PMID- 14972972
TI  - Growth and soluble proteins of cell cultures derived from explants and
      protoplasts of Pinus pinaster cotyledons.
AB  - Pinus pinaster Ait. cell suspension cultures were derived from chopped cotyledons
      and from cotyledon protoplasts. When transferred after 12 weeks in culture,
      growth of both cell types showed a lag of 5 days followed by an exponential phase
      of 14 days for the protoplast-derived cells and 23 days for the organ-derived
      cells. During the exponential growth phase, packed cell volume of protoplast
      derived cultures increased 7-fold and that of organ-derived cultures 13-fold.
      During the stationary phase, the diameters of protoplast-derived cells averaged
      80 microm and those of organ-derived cells 100 microm. After 30 days, the media
      containing protoplast-derived and organ-derived cells decreased in osmolarity by
      50 and 120 mOs per kg water, respectively, and in pH by 1.4 and 2.0 units,
      respectively. Throughout the growth cycle, protein content per unit of packed
      cell volume was always at least 35% higher in the protoplast-derived cultures
      than in the organ-derived cultures. Two-dimensional electrophoretic separation of
      soluble proteins revealed three peptides present in protoplast-derived cells that
      were absent from organ-derived cells and two peptides present in organ-derived
      cells that were absent from protoplast-derived cells. Other peptides differed
      quantitatively between the cell types.

PMID- 14972973
TI  - Pine needle holders for use in gas exchange measurements.
AB  - Simple holders for positioning pine needles in a gas exchange cuvette are
      described. The holders make it easy to enclose a standard length of needles in
      the cuvette in a single plane without mutual shading. The holders also make it
      possible, following gas exchange measurements, to harvest for further analysis
      just those needle portions that were enclosed in the leaf chamber. Field
      observations, which were made with a gas exchange cuvette incorporating the
      needle holders, on the relationship between carbon exchange rate and photon flux
      density in loblolly pine (Pinus taeda L.) needles are reported.

PMID- 14972974
TI  - Solar equivalent leaf area: an efficient biometrical parameter of individual
      leaves, trees and stands.
AB  - The solar equivalent leaf area (A(s)), a simply and easily determined biometrical
      parameter of leaves, trees and stands, was derived theoretically. The parameter
      is defined as projected leaf area weighted for the time integral of irradiance at
      a given location in the canopy relative to that of fully irradiated leaves at the
      top of the canopy. The efficiency of A(s) as a basis for estimating stand-area
      transpiration of a mature oak (Quercus robur L.) forest from measurements of
      transpiration by individual trees was compared with that of other stand and tree
      characteristics. Stand transpiration estimates based on A(s) were more precise
      and less prone to systematic error than estimates based on basal area, timber
      volume, projected tree crown area, projected leaf area, or leaf dry mass. Solar
      equivalent leaf area reflects both the amount and the physiological properties of
      leaves and can be used as a measure of tree size and functional capacity. It can
      be calculated from ordinary forest inventory data on trees and stands, adjusted
      according to simple phyllometric data. It appears to have wide application in
      ecological and forestry studies for relating the physiological characteristics of
      individual leaves to those of entire trees or stands.

PMID- 14972975
TI  - Relationships among cold hardiness, root growth potential and bud dormancy in
      three conifers.
AB  - Greenhouse-cultured, container-grown ponderosa pine (Pinus ponderosa var.
      scopulorum Engelm.), interior Douglas-fir (Pseudotsuga menziesii var. glauca
      (Beissn.) Franco) and Engelmann spruce (Picea engelmannii (Parry) Engelm.) were
      cold acclimated and deacclimated in growth chambers over 19 weeks. Stem cold
      hardiness, total new root length at 14 days and days to bud break were measured
      weekly. Relationships among cold hardiness, root growth potential (RGP) and bud
      dormancy suggest that cold hardiness, which can be measured quickly, could
      provide a useful basis for estimating the two other parameters. During cold
      acclimation, there was a lag period in which stem cold hardiness remained at -15
      degrees C and RGP was at a minimum, in all three species. Douglas-fir and
      Engelmann spruce buds remained fully dormant during this lag period. Ponderosa
      pine buds had no chilling requirement for the loss of dormancy, and reached
      quiescence during the lag period. Immediately following the lag period, as stem
      cold hardiness progressed to -22 degrees C, RGP increased to a high plateau in
      all three species, and Douglas-fir and Engelmann spruce buds approached
      quiescence. Cold deacclimation and bud development began immediately on exposure
      to warm, long days, but RGP remained high until stem cold hardiness returned to
      approximately -15 degrees C. At bud break, cold hardiness and RGP were at the
      minimum.

PMID- 14972976
TI  - Branch breakage under snow and ice loads.
AB  - Measurements were made on branches and trunks of Picea sitchensis (Bong.) Carr.
      to determine the relationship between (i) the bending moment at the bases of
      branches that cause breakage, and (ii) midpoint diameter cubed. The theory for
      cantilever beams was then used to calculate the basal bending moments and
      midpoint diameters of branches with different numbers of laterals and endpoint
      deflections, given previously measured values of Young's modulus, taper and
      weights of foliage and wood. Snow and ice loads (equal to 2 and 4 g cm(-1) of
      shoot, respectively) were then included in the calculation to determine whether
      the basal bending moments exceeded the breakage values. The likelihood of
      breakage increased with an increase in (i) number of laterals, and (ii) endpoint
      deflection under self weight (without snow or ice)-features that had previously
      been shown to lessen the amount of branch wood required to support a unit of
      foliage. However, branches which deflected moderately (> 10% of their length)
      under their own weight deflected greatly under snow or ice loads and might shed
      powdery snow before breakage occurs.

PMID- 14972977
TI  - Carbohydrate relations during propagation of cuttings from sexually mature Pinus
      banksiana trees.
AB  - Concentrations of glucose, sucrose, soluble reducing sugars, starch and total non
      structural carbohydrate were determined during propagation of cuttings from
      sexually mature Pinus banksiana Lamb. trees. Such cuttings rarely initiate
      adventitious roots whatever the method or duration of propagation. Terminals,
      needles, and upper and basal stem segments of cuttings were analyzed at Day 0 and
      every 2 days for 18 days. Comparison of the results with those of earlier studies
      with cuttings of P. banksiana seedlings, which root readily, indicated pronounced
      differences in carbohydrate concentrations and partitioning between the two types
      of cutting. Compared with those from seedlings, cuttings from sexually mature
      trees exhibited: (1) more total non-structural carbohydrate in each tissue at Day
      0; (2) decreasing rather than increasing total carbohydrate (mainly starch)
      concentrations in each tissue during propagation; (3) different carbohydrate
      concentration ratios in each tissue during propagation; and (4) higher sucrose
      concentrations in terminals during propagation, relative to concentrations at Day
      0. Cuttings from sexually mature trees also differed from cuttings of seedlings
      in having a much lower rate of dry matter accumulation during propagation. These
      findings suggest that the poor rooting ability of cuttings from sexually mature
      P. banksiana is not attributable to a lack of total carbohydrate, but that the
      rooting abilities of cuttings from seedlings and from sexually mature trees
      differ because of differences between the two types of cutting in rates of net
      photosynthesis and starch metabolism. The difference in starch metabolism becomes
      apparent during the first 2 days of propagation.

PMID- 14972978
TI  - Carbohydrate requirements of peach fruit growth and respiration.
AB  - Data on the seasonal patterns of fruit growth and dark respiration of two peach
      (Prunus persica (L.) Batsch) cultivars were combined with temperature data to
      calculate the carbohydrate requirements of an "average" peach fruit from bloom to
      harvest. The two peach cultivars used were June Lady (an early maturing (mid
      June) cultivar) and O'Henry (a late maturing (early-August) cultivar). At
      harvest, the mean dry weight of the June Lady fruit was 17.8 g (139.7 g fresh
      weight) and of O'Henry fruits was 30.9 g (213.9 g fresh weight), and the times
      from full bloom to harvest were 107 and 154 days, respectively. The total
      calculated fruit respiration requirements were 132 and 300 mmol CO(2) fruit(-1)
      season(-1) for June Lady and O'Henry fruits, respectively. Total calculated
      carbohydrate requirements for fruit growth and respiration are 23.9 and 43.8 g
      CH(2)O fruit(-1) season(-1) for June Lady and O'Henry fruits, respectively. Fruit
      respiration accounted for 16.3% of the total carbohydrate requirements of June
      Lady fruits and 0.5% of the total carbohydrate requirements of O'Henry fruits.

PMID- 14972979
TI  - Response of tree seedlings to aluminum.
AB  - This review focuses on the mechanisms underlying aluminum (Al) toxicity in trees.
      The major topics discussed include the uptake and localization of Al, effects of
      Al on growth and composition, factors determining the response to Al, proposed
      mechanisms of Al resistance, and the occurrence of Al phytotoxicity under field
      conditions.

PMID- 14972980
TI  - Turbulent transfer in a deciduous forest.
AB  - Carbon dioxide, water vapor and other passive scalars are physically transferred
      between a plant canopy and the atmosphere by turbulence. Intense and intermittent
      sweep and ejection events transfer most of the mass. Although the capacity for
      turbulence to transfer material is high, mass transfer is coupled to the
      diffusive source or sink strength of the foliage and soil and is ultimately
      limited to a minimum level set by the supply of material, or the demand for it.
      The diffusive source/sink strength of material leaving or entering leaves and the
      soil is a function of many physical, biological and chemical attributes and
      processes. These attributes and processes include the amount and distribution of
      foliage, the leaf boundary layer and surface resistances, the turbulence and
      radiative regimes in the canopy, biochemical and photochemical reactions and the
      scalar concentration field within and above the canopy and inside leaves and the
      soil. Here we discuss how these factors contribute to turbulent transfer in a
      deciduous forest.

PMID- 14972981
TI  - Seasonal changes in intensity of bud dormancy in loblolly pine seedlings.
AB  - The terminal buds of six-month-old loblolly pine (Pinus taeda L.) seedlings
      remained closed for approximately six months, although bud dormancy, as measured
      by rate of bud break in a standard greenhouse environment, was only exhibited for
      about one month. The peak of bud dormancy was in December for seedlings grown
      near Auburn, Alabama. However, the timing and intensity varied with seed source
      and may have been affected by the warm fall temperatures. Seedlings from the more
      northern provenances entered dormancy first and reached a deeper state of
      dormancy than seedlings from southern provenances. The rate of shoot elongation
      was not consistently related to the rate of bud break.

PMID- 14972982
TI  - Water relations of red spruce seedlings treated with acid mist.
AB  - Pressure-volume curves, day and night transpiration rates, needle drying curves,
      and shoot water potentials were determined for 2-year-old red spruce trees that
      had been exposed for three months to a range of acid mists (pH 2.5 to pH 5.0)
      containing equimolar (NH(4))(2)SO(4) and HNO(3). No effect of acid mist was
      observed on cuticular resistance or on the rates of day and night transpiration,
      although trees exposed to acid mist exhibited symptoms of mild water stress.
      Significant decreases in maximum turgor, the relative water content (RWC)
      associated with zero turgor, and bulk volumetric elastic modulus occurred as the
      pH of the mist decreased from 5.0 to 2.5. At all RWC values, there was an
      increase in solute potential as mist pH decreased. Shoot water potential declined
      with a decrease in pH of the mist.

PMID- 14972983
TI  - Leaf phosphorus and nitrogen concentrations and net photosynthesis in Eucalyptus
      seedlings.
AB  - Seedlings of Eucalyptus grandis Hill ex Maiden, E. pilularis Smith and E.
      gummifera (Sol. ex Gaertner) Hochr. were grown in solution culture with 100
      micromol phosphorus (P). After eight weeks, half of the seedlings were
      transferred to solution cultures containing 1 micromol P. After a further four
      weeks, growth, net photosynthesis and foliar P and nitrogen (N) concentrations
      were measured. The seeds of E. grandis came from a relatively fertile site and
      those of the other two species from phosphorus-deficient sites. Growth and net
      photosynthesis did not change in E. pilularis subjected to the low-P treatment,
      whereas in E. grandis, and to a limited extent in E. gummifera, the low-P
      treatment resulted in an increase in net photosynthesis that was associated with
      higher foliar N concentrations (especially protein-N), possibly as a result of
      nitrogen being retranslocated from the roots. In response to the low-P treatment,
      leaf phosphorus concentration was reduced by 50-60% in E. grandis and E.
      pilularis and by 20-30% in E. gummifera. Of the chemical fractions examined, the
      greatest decrease occurred in the inorganic-P pool. The data suggest that
      photosynthesis is not limited by leaf phosphorus concentrations typical of those
      found in Eucalyptus seedlings growing on phosphorus-deficient sites.

PMID- 14972984
TI  - Response of Ulmus americana seedlings to varying nitrogen and water status. 1
      Photosynthesis and growth.
AB  - Well-watered American elm (Ulmus americana L.) seedlings responded to increased
      nitrate availability with increased leaf nitrogen (N) concentration and
      photosynthetic rate, larger and more numerous leaves, greater total growth and
      greater proportional allocation of carbon to shoot than root. Plasticity of
      growth and carbon allocation were greater than plasticity of N concentration and
      photosynthetic capacity. For a given N availability, allocation of N per unit
      leaf area was positively correlated with dry mass per unit leaf area (specific
      leaf mass), but these relationships differed with N availability. Rates of net
      photosynthesis and leaf conductance declined logarithmically with decreasing
      predawn water status. Increased water stress resulted in a greater relative
      decline in net photosynthesis and leaf conductance for high-N than low-N plants.

PMID- 14972985
TI  - Response of Ulmus americana seedlings to varying nitrogen and water status. 2
      Water and nitrogen use efficiency in photosynthesis.
AB  - Photosynthetic utilization of water and nitrogen in Ulmus americana L. seedlings
      was tightly linked with the relative availability of each resource. During
      periodic drying cycles, water use efficiency increased as predawn water potential
      fell from -0.5 to -2.0 MPa. During the later stages of such drying cycles, the
      relative contribution of stomatal limitations to the total net photosynthetic
      limitation appeared to be at its greatest, whereas biochemical limitations were
      predominant in well-watered plants grown under low nitrogen (N) availability. For
      any level of leaf water status, water use efficiency of photosynthesis (WUE) was
      always greater in plants with high leaf N content than in plants with low leaf N
      content. Photosynthetic nitrogen use efficiency (PNUE) was always greater in
      plants with low leaf N content than in plants with high leaf N content, for any
      level of water status. In combined N treatments and predawn water status classes,
      there was a significant inverse relationship between PNUE and WUE.

PMID- 14972986
TI  - Seasonal changes in nodular nitrogenase activity of Alnus glutinosa and Elaeagnus
      angustifolia.
AB  - Root nodule development, and seasonal patterns of nodular nitrogenase and
      hydrogenase activities were determined for 5- to 8-year old black alder (Alnus
      glutinosa (L.) Gaertn.) and Russian olive (Elaeagnus angustifolia L.)
      interplanted with black walnut (Juglans nigra L.) on bottomland and upland sites
      in central Illinois, USA. Black alder produced nodules at both sites, but Russian
      olive did so only at the bottomland site. Nodular nitrogenase activity was
      detectable in both species over a 220-day period. Maximum, midday rates of
      nitrogenase activity (acetylene reduction) of 15 to 20 micromoles C(2)H(4) per g
      dry nodule per hour were maintained by black alder for approximately 150 days at
      both the upland and bottomland sites. Near maximum rates of nodular nitrogenase
      activity were maintained for a similar period by Russian olive at the lowland
      site, although specific nitrogenase activity was approximately 25% lower than in
      black alder owing to a larger proportion of necrotic nodular tissue in Russian
      olive. In both species, nitrogenase activity increased exponentially with
      temperature between 10 degrees C and 20 to 25 degrees C. No net hydrogen
      evolution by nodules of either species was detected at any time during the assay
      period, indicating efficient hydrogenase systems were operating under the
      conditions of the field assay. Height of black walnut interplanted with nodulated
      black alder and Russian olive was greater than that of black walnut grown in pure
      stands.

PMID- 14972987
TI  - The elasticity and vertical distribution of stress within stems of Picea
      sitchensis.
AB  - Eight 22-year-old Picea sitchensis (Bong.) Carr. trees growing in a Scottish
      forest were bent using a winch and cable. The shapes of the bent stems were
      modeled using the structural theory of a cantilever beam, with non-uniform stem
      taper and large deflections taken into account. The Young's modulus of elasticity
      for the stems was estimated to be 2.0-6.4 GPa, which is lower than that reported
      for sawn green timber of this species, but similar to that for intact green stem
      sections. The longitudinal distribution of stress along the stems had a maximum
      at a height that was dependent on taper. Maximum stress occurred higher up in the
      more tapered stems.

PMID- 14972988
TI  - Water stress and seedling growth of two eucalypt species from contrasting
      habitats.
AB  - Seedlings of Eucalyptus maculata Hook (mesic environment) and E. brockwayi C.A.
      Gardn. (arid environment) were supplied 100, 70 or 40% of their water
      requirements estimated from leaf area and the water used by well-watered
      seedlings. Restricting water supply caused large differences in growth rates,
      which were related to large differences in total leaf area. There was a fivefold
      range of variation in number of leaves per plant, and a reduction of up to 20% in
      average leaf size as a consequence of restricting water supply. Eucalyptus
      maculata seedlings produced more dry matter than E. brockwayi seedlings, but net
      assimilation rate was higher in E. brockwayi seedlings. Transpiration rates were
      also higher in E. brockwayi than in E. maculata. Leaf expansion was analyzed as a
      function of water stress integral (S(Psi)), which is the cumulative integral over
      time of predawn water potential below a datum. The leaf area achieved at any
      stress level was not uniquely dependent on total S(Psi), there was a secondary
      effect associated with reduced leaf growth caused by previous stress. At any
      value of S(Psi), reductions in leaf growth of water-stressed seedlings relative
      to leaf growth of well-watered control seedlings were greater in E. maculata
      seedlings than in E. brockwayi. Treatment differences in both species showed
      that, within the levels of stress applied, a moderate water stress over a long
      period of time was more detrimental to dry matter production than a severe stress
      for a short time.

PMID- 14972989
TI  - Shoot culture dynamics of six Populus clones.
AB  - Shoot tips of five genotypically diverse Populus clones, P. alba x P.
      grandidentata 'Crandon,' P. nigra 'Betulifolia' x P. trichocarpa, P. nigra x P.
      laurifolia 'Strathglass,' P. maximowiczii x P. trichocarpa 'Androscoggin' and P.
      deltoides x P. nigra 'Eugenei,' were collected from hardwood cuttings,
      sterilized,and established in vitro. Stable shoot cultures were obtained from all
      clones except P. deltoides x P. nigra 'Eugenei'. The four poplar clones that
      formed stable shoot cultures together with a previously established P. tremula
      'Erecta' clone were placed as two-node explants on either Murashige and Skoog
      medium or Woody Plant Medium containing benzyladenine to determine the rate of
      shoot multiplication, shoot growth and other responses of the clones. All five
      poplar clones showed rapid shoot multiplication when cultured in the presence of
      0.4-1.0 microM benzyladenine on Murashige and Skoog medium, although P. tremula
      'Erecta' produced a greater number of healthy shoots when grown on Woody Plant
      Medium. Individual shoot growth of all clones was more vigorous when the medium
      contained 0-0.1 microM benzyladenine, and 100% of such shoots rooted ex vitro.

PMID- 14972990
TI  - Ultrasound emission after cycles of water stress in Picea abies.
AB  - The relationships among rate of ultrasound acoustic emission (AE), xylem water
      potential and transpiration rate were investigated in 5-year-old potted saplings
      of Picea abies Karst. after cycles of water stress. Water-stressed plants
      displayed minimum xylem water potentials of -3.9 MPa, near-zero transpiration
      rates and up to 45 AE counts per minute. After rewatering, water-stressed plants
      no longer produced AEs. Well-watered control plants produced only a small number
      of ultrasonic AEs. After three cycles of water stress (lasting 24 days in total),
      it was estimated that about two-thirds of the functional tracheids were
      embolized. The concomitant reduction in hydraulic conductance was about 70%.

PMID- 14972991
TI  - Temporal allocation of (14)C to extramatrical hyphae of ectomycorrhizal ponderosa
      pine seedlings.
AB  - Ponderosa pine seedlings were inoculated with Hebeloma crustuliniforme either in
      growth pouches before they were transplanted to root-mycocosms (P seedlings), or
      at the time of transfer to root-mycocosms (V seedlings). Uninoculated seedlings
      served as controls (U seedlings). The use of root-mycocosms allowed examination
      of portions of hyphae separate from roots and rooting substrate but still in
      symbiosis with the host. The results thus provided a quantitative basis for
      estimating hyphal mass and carbon allocation to extramatrical hyphae. The amount
      of (14)CO(2) fixed after a 2-h exposure was greatest for P seedlings and least
      for uninoculated seedlings. Four and nine days after exposure, (14)C content was
      greatest in uninoculated seedlings and least in inoculated seedlings. In isotope
      distribution and dry mass accumulation, V seedlings were more similar to U than
      to P seedlings. Calculated on a dry weight basis, the allocation of isotope to
      mycelium suggested that extramatrical hyphae of P seedlings were a stronger sink
      for carbon than extramatrical hyphae of V seedlings. Differences in inoculation
      methods resulted in differences in carbon allocation and physiology of
      extramatrical hyphae that could affect seedling establishment and survival.
      Seedlings inoculated by one method cannot serve as surrogates for mycorrhizal
      seedlings produced by other inoculation techniques.

PMID- 14972992
TI  - Gas exchange responses of two Eucalyptus species to salinity and waterlogging.
AB  - The effects of salinity and waterlogging on stomatal conductance, net
      photosynthesis and transpiration of 3-month-old Eucalyptus camaldulensis Dehnh.
      and Eucalyptus lesouefii Maiden seedlings were studied under greenhouse
      conditions. Under non-saline conditions, waterlogging induced stomatal closure in
      both species. However, the stomata of E. camaldulensis reopened after five weeks,
      when adventitious roots were produced. Relative to that of controls, height
      growth of waterlogged seedlings was greater in E. camaldulensis than in E.
      lesouefii, as were rates of photosynthesis and transpiration. In a freely drained
      medium, high salinity reduced rates of seedling height growth and photosynthesis,
      relative to those in controls, less in E. lesouefii than in E. camaldulensis. In
      both species, height growth, stomatal conductance and photosynthetic rate were
      lowest under conditions of saline waterlogging.

PMID- 14972993
TI  - Selection for salt and drought tolerance in protoplast- and explant-derived
      tissue cultures of Colt cherry (Prunus avium x pseudocerasus).
AB  - Colt cherry (Prunus avium x pseudocerasus) callus cultures were derived from leaf
      protoplasts, protoplasts of root cell suspension cultures, or by direct culture
      of leaf and root tissues. Survival of calli cultured on basal proliferation
      medium containing 25, 50, 100 or 200 mN (millinormal) NaCl, Na(2)SO(4) or KCl, or
      iso-osmotic (with NaCl) concentrations of mannitol ranged from 1 to 15%. After
      six transfers on the same medium, surviving cell lines were subjected to three
      cycles of direct recurrent selection; i.e., in each cycle, they were cultured
      alternately on basal proliferation medium, and on basal proliferation medium
      supplemented with NaCl, KCl, Na(2)SO(4) or mannitol. Salt- or mannitol-tolerant
      cell lines selected in this way had smaller cells than unselected cell lines, and
      they grew more rapidly and had higher callus and cell survival rates than
      unselected cell lines when cultured in the presence of salt or mannitol. Cells
      lines selected for tolerance to one agent (sodium salt, potassium salt or
      mannitol) showed minimal tolerance to another agent. However, when plants were
      regenerated from salt- or mannitol-tolerant callus and new cultures derived from
      them, the new cultures showed tolerance to all of the salts and mannitol. Plant
      regeneration from the new cultures was not achieved under the conditions that led
      to the regeneration of the parent plants from callus.

PMID- 14972994
TI  - Aboveground production and N and P use by Larix occidentalis and Pinus contorta
      in the Washington Cascades, USA.
AB  - Aboveground net primary production (ANPP) and N and P use patterns were
      determined for western larch (Larix occidentalis Nutt.), a deciduous conifer, and
      lodgepole pine (Pinus contorta Dougl. var. latifolia Engelm.), an evergreen
      conifer, in the Cascade Mountains of Washington, USA. Western larch and lodgepole
      pine retranslocated 87 and 66% of foliage N and 66 and 78% of foliage P,
      respectively. At the stand level, N use efficiency of western larch was greater
      than that of lodgepole pine, whereas P use efficiency of lodgepole pine was
      greater than that of western larch. Western larch and lodgepole pine were
      comparable in ANPP and production efficiency (ANPP/foliage mass) if needle
      longevity is considered. The similarity in ANPP of the evergreen lodgepole pine
      and the deciduous western larch may be related in part to the lower initial
      construction cost of the foliage, and the efficient use of nitrogen by western
      larch.

PMID- 14972995
TI  - Comparative analysis of photosynthetic light environments within the crowns of
      juvenile rain forest trees.
AB  - Irradiances within the crowns of saplings of two tropical tree species were
      simultaneously compared in primary rain forest in Costa Rica. The species
      examined, Minquartia guianensis Aubl., a relatively slow-growing, canopy species,
      and Pithecellobium pedicellare (DC) Benth., a less-tolerant, emergent species,
      have different crown and leaf display patterns. Crown light environments were
      assessed by placing arrays of quantum sensors among leaves and recording at 5-s
      intervals for seven days with microloggers. Median total daily quantum flux
      densities for saplings of both species were less than 2% of full sun and did not
      differ significantly. More than 90% of the measurements within the crowns of
      these saplings were less than 25 micromol m(-2) s(-1). Spatial variability of
      photon flux densities within sapling crowns was similar for the two species
      despite differences in leaf display patterns. In saplings of both species, photon
      flux densities varied significantly over the relatively short distances within
      crowns and from day to day. Height growth of both species was significantly
      correlated with total daily photon flux densities and with percentage of full
      sun. However, only the tolerant species, Minquartia, showed a significant
      correlation between diameter growth and crown light environment.

PMID- 14972996
TI  - Frost hardiness of Picea rubens growing in spruce decline regions of the
      Appalachians.
AB  - It has been proposed that pollutants predispose Picea rubens Sarg. growing in the
      high Appalachians to frost damage. The pattern of autumn hardening of P. rubens
      growing at Whiteface Mountain, NY, and Newfound Gap, NC, was monitored by
      detaching shoots at 1-3 weekly intervals, air freighting them to Scotland, and
      freeze-testing them. The temperatures that produced freezing injury from August
      1986 to January 1987 were compared with minimum air temperatures recorded in
      those months at nearby meteorological stations over 22 previous years. There was
      only weak evidence that the onset or degree of frost hardening was inadequate to
      protect the trees from direct freezing injury (as opposed to winter desiccation).
      Historically, minimum air temperatures occasionally fell below the lethal
      temperature for a 10% kill (LT(10)), but they rarely fell below the LT(50). The
      trees hardened rapidly in the autumn (max. 2.2 degrees C day(-1)) to between -30
      degrees C and -40 degrees C by January (LT(50)), including trees showing visible
      decline on Clingman's Dome, TN. Individual trees differed in hardiness by up to
      10 degrees C. It is concluded that any pollutant-induced susceptibility to
      freezing injury is insufficient, on its own, to account for forest decline in the
      Appalachians.

PMID- 14972997
TI  - Sucrose metabolic pathways in sweetgum and pecan seedlings.
AB  - Sucrose metabolism and glycolysis were studied in one- to two-year-old seedlings
      of sweetgum (Liquidambar styraciflua L.) and pecan (Curya illinoinensis
      (Wangenh.) C. Koch). The sucrose synthase pathway was identified as the dominant
      sucrose metabolic activity in sucrose sink tissues such as terminal buds and the
      root cambial zone. The sucrose synthase pathway was completely dependent on
      uridine diphosphate and pyrophosphate and it was activated by fructose 2,6
      bisphosphate. Both acid and neutral invertases were less active than sucrose
      synthase in sucrose sink tissues. According to the magnitude of seasonal changes
      in activity, sucrose synthase, the pyrophosphate-dependent phosphofructokinase,
      and fructokinase were identified as adaptive enzymes, whereas neutral invertase,
      uridine diphosphate-glucopyrophosphorylase, phosphoglucomutase, and the
      nonspecific, nucleotide triphosphate-dependent phosphofructokinase were
      identified as maintenance enzymes. The periodically high activities of
      pyrophosphate-dependent phosphofructokinase indicate that pyrophosphate can serve
      as an energy source in trees. The observations support the hypothesis that
      sucrose glycolysis and gluconeogenesis in plants proceed by a network of
      alternative enzymes and substrates.

PMID- 14972998
TI  - Removal of ethanol from lodgepole pine roots.
AB  - The removal of ethanol from flooded tree roots was examined in three provenances
      of lodgepole pine (Pinus contorta) Dougl. Less than 0.2% of the ethanol generated
      by the roots escaped by the gaseous pathway provided by the lenticels. A large
      proportion, however, was transported from the roots in the transpiration stream.
      Gas chromatographic detection of ethanol emanating from the lenticels provided a
      sensitive indicator of oxygen deficits in the roots.

PMID- 14972999
TI  - Evidence of cytokinin bases, ribosides and glucosides in roots of Douglas-fir,
      Pseudotsuga menziesii.
AB  - Concentrations of cytokinin-like compounds were measured in root tips of Douglas
      fir (Pseudotsuga menziesii (Mirb.) Franco) collected in spring. Cytokinin bases
      and ribosides were estimated by radioimmunoassay after purification by
      immunoaffinity (zeatin riboside and isopentenyladenosine antibodies coupled to
      cellulose gel) and high performance liquid chromatography. Cytokinin glucosides
      were similarly analyzed in root extracts treated with beta-glucosidase and
      octadecyl-silica column chromatography in conjunction with immunoaffinity
      purification. The identity of predominant cytokinins obtained after enzymatic
      degradation was confirmed by gas chromatography-mass spectrometry. Each of the
      observed cytokinin bases and ribosides seemed to have a corresponding hexose
      conjugate form. Total quantity of cytokinin glucosides was twice that of
      cytokinin bases and ribosides, and the major compound was isopentenyladenosine
      hexose conjugate.

PMID- 14973000
TI  - Root hydraulic conductivity and root growth capacity of black spruce (Picea
      mariana) seedlings.
AB  - The relationship between root elongation and root hydraulic conductivity was
      investigated in 1-year-old, overwintered black spruce (Picea mariana (Mill.)
      seedlings. Hydraulic conductivity was estimated by observing water flux through
      decapitated roots under positive pressure. Five hydraulic conductivity parameters
      were estimated: (1) water flux under a minimal pressure of 0.2 MPa (J(v, min));
      (2) pressure at which a linear relationship between water flux and pressure began
      (P(min)); (3) slope of the linear water flux-pressure relationship (L(v)); (4)
      pressure at which the linear relationship between water flux and pressure ended
      (P(max)); and (5) maximum water flux (J(v, max)). Between day 1 and day 2 after
      thawing of the growing medium, there were significant increases in L(v) and J(v,
      max) but there was little, if any, root elongation. Root elongation averaged 5.4
      cm seedling(-1) 5 days after thawing and 88.2 cm seedling(-1) 20 days after
      thawing. Root hydraulic conductivity increased with new root length initially.
      But between days 20 and 30, when new root length nearly doubled, P(min) was the
      only measure of hydraulic conductivity that increased significantly. There were
      significant correlations (P < 0.05) between white root length and both J(v, min)
      (r(2) = 0.90) and J(v, max) (r(2) = 0.91).

PMID- 14973001
TI  - Harvest index in northern temperate cultivated conifers.
AB  - Harvest index is defined and its relationship with primary production, biomass
      partitioning and yield components in forest trees examined. As stand density has
      been found to have a major effect on harvest index, it is concluded that further
      development of the harvest index concept in forest trees will need to take
      account of density-yield relationships.

PMID- 14973002
TI  - Process modeling of nitrogen effects on carbon assimilation and allocation-a
      review.
AB  - Maximum forest productivity will only be realized through intensified management
      of mineral nutrition. This review examines selected individual tree and stand
      nutrition models. Nutrient supply is defined by mass flow and diffusion processes
      in a forest environment. Additionally, structures of biomass accumulation models
      are considered as well as nutritional limitations on assimilation functions and
      carbon allocation patterns.

PMID- 14973003
TI  - Structure and function of flexure wood in Abies fraseri.
AB  - Wood produced during flexure in one-year-old leaders of Abies fraseri (Pursh)
      Poir. (Fraser fir) was analyzed anatomically and radio-densitometrically. More
      xylem cells were produced in stems subjected to flexing than in stems that were
      not flexed. The lumens of tracheids produced in response to flexure were smaller
      than the lumens of tracheids in normal wood. This was manifest as an increase in
      the cell wall area/cell lumen area ratio. Microfibril orientation in flexure
      induced wood approached the less extreme values found in compression wood. The
      growth ring composed of flexure-induced wood also had a greater density than
      normal wood. Compression wood, as defined by cellular characteristics observed in
      transverse section, was absent in flexed stems. Detailed analysis of the
      anatomical structure, wood density and biomechanical properties of flexure
      induced wood indicated that it has more in common with compression wood than with
      normal wood.

PMID- 14973004
TI  - Variation in growth and osmotic regulation of roots of water-stressed maritime
      pine (Pinus pinaster Ait.) provenances.
AB  - Hydroponically cultivated Pinus pinaster Ait. seedlings of a drought-sensitive
      population from France (Landes) and of a more drought-adapted population from
      Morocco (Tamjoute) were subjected to a progressive increase in water stress by
      additions of an osmoticum (polyethylene glycol 600) to the nutrient solution. The
      final osmotic potential (Psi(ms)) of the nutrient solution was achieved over a
      period of up to 6 days, and ranged from -0.03 (control, no added osmoticum) to 
      0.8 MPa. In the 6 days during which water stress was imposed, roots elongated
      faster in the Moroccan provenance than in the French provenance, but the applied
      water deficits did not inhibit root elongation in either population. Among
      treatments, root dry weight per unit root length, total root dry weight and
      root/shoot dry weight ratio increased with decreasing Psi(ms) in both
      provenances. Both the water potential (Psi(w)) of the roots (apices) and the
      water potential difference between the roots and the nutrient solution decreased
      as Psi(ms) decreased. The reduction in Psi(w) was matched by a decrease of
      comparable magnitude in cell osmotic potential (Psi(pi)) so that root turgor was
      unaffected by the Psi(ms). Osmotic adjustment was greater, however, in the
      Moroccan provenance than in the French provenance. Consequently, under the
      osmotically imposed water stress, the water potential difference between root and
      nutrient solution was greater in the Moroccan provenance than in the French
      provenance. Similar changes in plant water relations were observed when seedlings
      were grown in drying sand.

PMID- 14973005
TI  - The dynamics of rooting in Triplochiton scleroxylon cuttings: their relation to
      leaf area, node position, dry weight accumulation, leaf water potential and
      carbohydrate composition.
AB  - Single-node, leafy stem cuttings of Triplochiton scleroxylon K. Schum. were
      collected from successive nodes down the uppermost shoot of 2-shoot stockplants.
      The leaves were trimmed to 10, 50 and 100 cm(2) before the cuttings were set
      under intermittent mist to root. Batches of cuttings were harvested after 0, 14,
      28 and 42 days to assess leaf water potential, dry weight and carbohydrate
      content of their leaf and stem portions. Cuttings with leaf areas of 10, 50 and
      100 cm(2) increased in total dry weight by 29, 61 and 90%, respectively, during
      the 6-week period. The increase in dry weight was accompanied by increases in
      reflux-extracted soluble carbohydrates (RSC), water-soluble carbohydrates (WSC)
      and starch. By contrast, increase in leaf area reduced leaf water potential of
      cuttings before root emergence. Fewer large-leaved cuttings rooted than smaller
      leaved cuttings, suggesting that rooting ability is at least partially determined
      by the balance between photosynthesis and transpiration. Fewer roots per cutting
      were produced on cuttings with 10 cm(2) leaves than on cuttings with larger
      leaves. Node position affected increments in dry weight, carbohydrate content and
      leaf water potential, with differences between nodes on day 0 generally being
      lost or slightly reversed by day 14. Rooting ability was not related to initial
      (day 0) carbohydrate content, suggesting that rooting is dependent on
      carbohydrates formed after severance. During the rooting period, the proportions
      of total non-structural carbohydrate as WSC and starch were reversed, from mostly
      WSC on day 0 to mostly starch by day 42. These changes in WSC and starch occurred
      most rapidly in large-leaved cuttings.

PMID- 14973007
TI  - An evaluation of case-based teaching: evidence for continuing benefit and
      realization of aims.
AB  - A cross-sectional evaluation of case-based teaching (CBT), a novel physiology
      learning environment for medical undergraduates, revealed that second, third, and
      fourth year students, together with their tutors, valued CBT as an experience
      that met its three major aims. The initiative not only integrated physiology with
      related basic sciences and clinical medicine but importantly linked students'
      developing knowledge of theory to practice. CBT was also valued by students as
      their first introduction to clinical skills, with most tutors believing that it
      was the nonthreatening environment that helped students gain confidence for their
      first "real patient" encounters. The greatest support for CBT came from third
      year medical students, at the crossroads between their preclinical and clinical
      environments. Fourth year students, now encountering real patients, had moved on
      to developing their skills in the hospital environment.

PMID- 14973008
TI  - An introductory biology lab that uses enzyme histochemistry to teach students
      about skeletal muscle fiber types.
AB  - One important goal of introductory biology laboratory experiences is to engage
      students directly in all steps in the process of scientific discovery. Even when
      laboratory experiences are built on principles discussed in the classroom,
      students often do not adequately apply this background to interpretation of
      results they obtain in lab. This disconnect has been described at the level of
      medical education (4), so it should not be surprising that educators have
      struggled with this same phenomenon at the undergraduate level. We describe a new
      introductory biology lab that challenges students to make these connections. The
      lab utilizes enzyme histochemistry and morphological observations to draw
      conclusions about the composition of functionally different types of muscle
      fibers present in skeletal muscle. We report that students were not only
      successful at making these observations on a specific skeletal muscle, the
      gastrocnemius of the frog Rana pipiens, but that they were able to connect their
      results to the principles of fiber type differences that exist in skeletal
      muscles in all vertebrates.

PMID- 14973009
TI  - Simplification of rat intubation on inclined metal plate.
AB  - Small-animal intubation is often necessary during inhalation anesthesia to allow
      steady-state conditions for large operations and in vivo experiments in all
      fields of experimental surgery. In rats, placing an orotracheal tube is
      technically difficult primarily because of the small size of the subject and the
      lack of equipment specifically designed for this task. We describe a simple rat
      intubation technique in which the animal is suspended in dorsal recumbency on an
      inclined metal plate. The animal, anesthetized with ether, is fixed to a 70
      degrees-inclined metal plate in a dorsal position by means of a Mersilene ribbon
      hooked around the upper incisors. This method of positioning the animal is the
      most important step in the intubation process and further facilitates the
      technique already described by other authors. A human otoscope was used as a
      laryngoscope, intubation was performed using the Seldinger technique, and a 14
      gauge intravenous catheter served as an endotracheal tube. This inexpensive
      technique is quickly learned and can be used in any laboratory. Safe and reliable
      airway management can thus be achieved, permitting in vivo examinations and
      operations.

PMID- 14973010
TI  - Simple, inexpensive model spirometer for understanding ventilation volumes.

PMID- 14973011
TI  - The examination post mortem: a teaching opportunity.

PMID- 14973012
TI  - Characterization of two kinases involved in thiamine pyrophosphate and pyridoxal
      phosphate biosynthesis in Bacillus subtilis: 4-amino-5-hydroxymethyl
      2methylpyrimidine kinase and pyridoxal kinase.
AB  - Two Bacillus subtilis genes encoding two proteins (currently annotated ThiD and
      YjbV) were overexpressed and characterized. YjbV has 4-amino-5-hydroxymethyl-2
      methylpyrimidine and 4-amino-5-hydroxymethyl-2-methylpyrimidine pyrophosphate
      kinase activity and should be reannotated ThiD, and B. subtilis ThiD has
      pyridoxine, pyridoxal, and pyridoxamine kinase activity and should be reannotated
      PdxK.

PMID- 14973013
TI  - Development of surface adhesion in Caulobacter crescentus.
AB  - Caulobacter crescentus has a dimorphic life cycle composed of a motile stage and
      a sessile stage. In the sessile stage, C. crescentus is often found tightly
      attached to a surface through its adhesive holdfast. In this study, we examined
      the contribution of growth and external structures to the attachment of C.
      crescentus to abiotic surfaces. We show that the holdfast is essential but not
      sufficient for optimal attachment. Rather, adhesion in C. crescentus is a complex
      developmental process. We found that the attachment of C. crescentus to surfaces
      is cell cycle regulated and that growth or energy or both are essential for this
      process. The initial stage of attachment occurs in swarmer cells and is
      facilitated by flagellar motility and pili. Our results suggest that strong
      attachment is mediated by the synthesis of a holdfast as the swarmer cell
      differentiates into a stalked cell.

PMID- 14973014
TI  - Evolution of a pathway to novel long-chain carotenoids.
AB  - Using methods of laboratory evolution to force the C(30) carotenoid synthase CrtM
      to function as a C(40) synthase, followed by further mutagenesis at functionally
      important amino acid residues, we have discovered that synthase specificity is
      controlled at the second (rearrangement) step of the two-step reaction. We used
      this information to engineer CrtM variants that can synthesize previously unknown
      C(45) and C(50) carotenoid backbones (mono- and diisopentenylphytoenes) from the
      appropriate isoprenyldiphosphate precursors. With this ability to produce new
      backbones in Escherichia coli comes the potential to generate whole series of
      novel carotenoids by using carotenoid-modifying enzymes, including desaturases,
      cyclases, hydroxylases, and dioxygenases, from naturally occurring pathways.

PMID- 14973015
TI  - Evidence for HrpXo-dependent expression of type II secretory proteins in
      Xanthomonas oryzae pv. oryzae.
AB  - Xanthomonas oryzae pv. oryzae is a causal agent of bacterial leaf blight of rice.
      Recently, an efficient hrp-inducing medium, XOM2, was established for this
      bacterium. In this medium, more than 10 proteins were secreted from the wild-type
      strain of X. oryzae pv. oryzae. Many of these proteins disappeared or decreased
      in amount in culture on XOM2 when incubated with the strain that has a mutation
      in the hrp regulatory gene. Interestingly, the secretory protein profile of a
      mutant lacking a type III secretion system (TTSS), components of which are
      encoded by hrp genes, was similar to that of the wild-type strain except that a
      few proteins had disappeared. This finding suggests that many HrpXo-dependent
      secretory proteins are secreted via systems other than the TTSS. By isolating
      mutant strains lacking a type II secretion system, we examined this hypothesis.
      As expected, many of the HrpXo-dependent secretory proteins disappeared or
      decreased when the mutant was cultured in XOM2. By determining the N-terminal
      amino acid sequence, we identified one of the type II secretory proteins as a
      cysteine protease homolog, CysP2. Nucleotide sequence analysis revealed that
      cysP2 has an imperfect plant-inducible-promoter box, a consensus sequence which
      HrpXo regulons possess in the promoter region, and a deduced signal peptide
      sequence at the N terminus. By reverse transcription-PCR analysis and examination
      of the expression of CysP2 by using a plasmid harboring a cysP2::gus fusion gene,
      HrpXo-dependent expression of CysP2 was confirmed. Here, we reveal that the hrp
      regulatory gene hrpXo is also involved in the expression of not only hrp genes
      and type III secretory proteins but also some type II secretory proteins.

PMID- 14973016
TI  - VirB1 orthologs from Brucella suis and pKM101 complement defects of the lytic
      transglycosylase required for efficient type IV secretion from Agrobacterium
      tumefaciens.
AB  - Type IV secretion systems mediate conjugative plasmid transfer as well as the
      translocation of virulence factors from various gram-negative pathogens to
      eukaryotic host cells. The translocation apparatus consists of 9 to 12
      components, and the components from different organisms are believed to have
      similar functions. However, orthologs to proteins of the prototypical type IV
      system, VirB of Agrobacterium tumefaciens, typically share only 15 to 30%
      identical amino acids, and functional complementation between components of
      different type IV secretion systems has not been achieved. We here report a
      heterologous complementation in the case of A. tumefaciens virB1 defects with its
      orthologs from Brucella suis (VirB1s) and the IncN plasmid pKM101 (TraL). In
      contrast, expression of the genes encoding the VirB1 orthologs from the IncF
      plasmid (open reading frame 169) and from the Helicobacter pylori cag
      pathogenicity island (HP0523) did not complement VirB1 functions. The
      complementation of VirB1 activity was assessed by T-pilus formation, by tumor
      formation on wounded plants, by IncQ plasmid transfer, and by IncQ plasmid
      recipient assay. Replacement of the key active-site Glu residue by Ala abolished
      the complementation by VirB1 from B. suis and by TraL, demonstrating that
      heterologous complementation requires an intact lytic transglycosylase active
      site. In contrast, the VirB1 active-site mutant from A. tumefaciens retained
      considerable residual activity in various activity assays, implying that this
      protein exerts additional effects during the type IV secretion process.

PMID- 14973017
TI  - Identification of a 349-kilodalton protein (Gli349) responsible for cytadherence
      and glass binding during gliding of Mycoplasma mobile.
AB  - Several mycoplasma species are known to glide in the direction of the membrane
      protrusion (head-like structure), but the mechanism underlying this movement is
      entirely unknown. To identify proteins involved in the gliding mechanism, protein
      fractions of Mycoplasma mobile were analyzed for 10 gliding mutants isolated
      previously. One large protein (Gli349) was observed to be missing in a mutant m13
      deficient in hemadsorption and glass binding. The predicted amino acid sequence
      indicated a 348,758-Da protein that was truncated at amino acid residue 1257 in
      the mutant. Immunofluorescence microscopy with a monoclonal antibody showed that
      Gli349 is localized at the head-like protrusion's base, which we designated the
      cell neck, and immunoelectron microscopy established that the Gli349 molecules
      are distributed all around this neck. The number of Gli349 molecules on a cell
      was estimated by immunoblot analysis to be 450 +/- 200. The antibody inhibited
      both the hemadsorption and glass binding of M. mobile. When the antibody was used
      to treat gliding mycoplasmas, the gliding speed and the extent of glass binding
      were inhibited to similar extents depending on the concentration of the antibody.
      This suggested that the Gli349 molecule is involved not only in glass binding for
      gliding but also in movement. To explain the present results, a model for the
      mechanical cycle of gliding is discussed.

PMID- 14973018
TI  - Cardiolipin domains in Bacillus subtilis marburg membranes.
AB  - Recently, use of the cardiolipin (CL)-specific fluorescent dye 10-N-nonyl
      acridine orange (NAO) revealed CL-rich domains in the Escherichia coli membrane
      (E. Mileykovskaya and W. Dowhan, J. Bacteriol. 182: 1172-1175, 2000). Staining of
      Bacillus subtilis cells with NAO showed that there were green fluorescence
      domains in the septal regions and at the poles. These fluorescence domains were
      scarcely detectable in exponentially growing cells of the clsA-disrupted mutant
      lacking detectable CL. In sporulating cells with a wild-type lipid composition,
      fluorescence domains were observed in the polar septa and on the engulfment and
      forespore membranes. Both in the clsA-disrupted mutant and in a mutant with
      disruptions in all three of the paralogous genes (clsA, ywjE, and ywiE) for CL
      synthase, these domains did not vanish but appeared later, after sporulation
      initiation. A red shift in the fluorescence due to stacking of two dye molecules
      and the lipid composition suggested that a small amount of CL was present in
      sporulating cells of the mutants. Mass spectrometry analyses revealed the
      presence of CL in these mutant cells. At a later stage during sporulation of the
      mutants the frequency of heat-resistant cells that could form colonies after heat
      treatment was lower. The frequency of sporulation of these cells at 24 h after
      sporulation initiation was 30 to 50% of the frequency of the wild type. These
      results indicate that CL-rich domains are present in the polar septal membrane
      and in the engulfment and forespore membranes during the sporulation phase even
      in a B. subtilis mutant with disruptions in all three paralogous genes, as well
      as in the membranes of the medial septa and at the poles during the exponential
      growth phase of wild-type cells. The results further suggest that the CL-rich
      domains in the polar septal membrane and engulfment and forespore membranes are
      involved in sporulation.

PMID- 14973019
TI  - Genomic and genetic analysis of Bordetella bacteriophages encoding reverse
      transcriptase-mediated tropism-switching cassettes.
AB  - Liu et al. recently described a group of related temperate bacteriophages that
      infect Bordetella subspecies and undergo a unique template-dependent, reverse
      transcriptase-mediated tropism switching phenomenon (Liu et al., Science 295:
      2091-2094, 2002). Tropism switching results from the introduction of single
      nucleotide substitutions at defined locations in the VR1 (variable region 1)
      segment of the mtd (major tropism determinant) gene, which determines specificity
      for receptors on host bacteria. In this report, we describe the complete
      nucleotide sequences of the 42.5- to 42.7-kb double-stranded DNA genomes of three
      related phage isolates and characterize two additional regions of variability.
      Forty-nine coding sequences were identified. Of these coding sequences, bbp36
      contained VR2 (variable region 2), which is highly dynamic and consists of a
      variable number of identical 19-bp repeats separated by one of three 5-bp
      spacers, and bpm encodes a DNA adenine methylase with unusual site specificity
      and a homopolymer tract that functions as a hotspot for frameshift mutations.
      Morphological and sequence analysis suggests that these Bordetella phage are
      genetic hybrids of P22 and T7 family genomes, lending further support to the idea
      that regions encoding protein domains, single genes, or blocks of genes are
      readily exchanged between bacterial and phage genomes. Bordetella bacteriophages
      are capable of transducing genetic markers in vitro, and by using animal models,
      we demonstrated that lysogenic conversion can take place in the mouse respiratory
      tract during infection.

PMID- 14973020
TI  - A dominant-negative fur mutation in Bradyrhizobium japonicum.
AB  - In many bacteria, the ferric uptake regulator (Fur) protein plays a central role
      in the regulation of iron uptake genes. Because iron figures prominently in the
      agriculturally important symbiosis between soybean and its nitrogen-fixing
      endosymbiont Bradyrhizobium japonicum, we wanted to assess the role of Fur in the
      interaction. We identified a fur mutant by selecting for manganese resistance.
      Manganese interacts with the Fur protein and represses iron uptake genes. In the
      presence of high levels of manganese, bacteria with a wild-type copy of the fur
      gene repress iron uptake systems and starve for iron, whereas fur mutants fail to
      repress iron uptake systems and survive. The B. japonicum fur mutant, as
      expected, fails to repress iron-regulated outer membrane proteins in the presence
      of iron. Unexpectedly, a wild-type copy of the fur gene cannot complement the fur
      mutant. Expression of the fur mutant allele in wild-type cells leads to a fur
      phenotype. Unlike a B. japonicum fur-null mutant, the strain carrying the
      dominant-negative fur mutation is unable to form functional, nitrogen-fixing
      nodules on soybean, mung bean, or cowpea, suggesting a role for a Fur-regulated
      protein or proteins in the symbiosis.

PMID- 14973021
TI  - Transcriptional profiling of Caulobacter crescentus during growth on complex and
      minimal media.
AB  - Microarray analysis was used to examine gene expression in the freshwater
      oligotrophic bacterium Caulobacter crescentus during growth on three standard
      laboratory media, including peptone-yeast extract medium (PYE) and minimal salts
      medium with glucose or xylose as the carbon source. Nearly 400 genes
      (approximately 10% of the genome) varied significantly in expression between at
      least two of these media. The differentially expressed genes included many
      encoding transport systems, most notably diverse TonB-dependent outer membrane
      channels of unknown substrate specificity. Amino acid degradation pathways
      constituted the largest class of genes induced in PYE. In contrast, many of the
      genes upregulated in minimal media encoded enzymes for synthesis of amino acids,
      including incorporation of ammonia and sulfate into glutamate and cysteine.
      Glucose availability induced expression of genes encoding enzymes of the Entner
      Doudoroff pathway, which was demonstrated here through mutational analysis to be
      essential in C. crescentus for growth on glucose. Xylose induced expression of
      genes encoding several hydrolytic exoenzymes as well as an operon that may encode
      a novel pathway for xylose catabolism. A conserved DNA motif upstream of many
      xylose-induced genes was identified and shown to confer xylose-specific
      expression. Xylose is an abundant component of xylan in plant cell walls, and the
      microarray data suggest that in addition to serving as a carbon source for growth
      of C. crescentus, this pentose may be interpreted as a signal to produce enzymes
      associated with plant polymer degradation.

PMID- 14973022
TI  - Assembly of an oxalate decarboxylase produced under sigmaK control into the
      Bacillus subtilis spore coat.
AB  - Over 30 polypeptides are synthesized at various times during sporulation in
      Bacillus subtilis, and they are assembled at the surface of the developing spore
      to form a multilayer protein structure called the coat. The coat consists of
      three main layers, an amorphous undercoat close to the underlying spore cortex
      peptidoglycan, a lamellar inner layer, and an electron-dense striated outer
      layer. The product of the B. subtilis oxdD gene was previously shown to have
      oxalate decarboxylase activity when it was produced in Escherichia coli and to be
      a spore constituent. In this study, we found that OxdD specifically associates
      with the spore coat structure, and in this paper we describe regulation of its
      synthesis and assembly. We found that transcription of oxdD is induced during
      sporulation as a monocistronic unit under the control of sigma(K) and is
      negatively regulated by GerE. We also found that localization of a functional
      OxdD-green fluorescent protein (GFP) at the surface of the developing spore
      depends on the SafA morphogenetic protein, which localizes at the interface
      between the spore cortex and coat layers. OxdD-GFP localizes around the
      developing spore in a cotE mutant, which does not assemble the spore outer coat
      layer, but it does not persist in spores produced by the mutant. Together, the
      data suggest that OxdD-GFP is targeted to the interior layers of the coat.
      Additionally, we found that expression of a multicopy allele of oxdD resulted in
      production of spores with increased levels of OxdD that were able to degrade
      oxalate but were sensitive to lysozyme.

PMID- 14973023
TI  - Role of histone-like protein H-NS in multidrug resistance of Escherichia coli.
AB  - The histone-like protein H-NS is a major component of the bacterial nucleoid and
      plays a crucial role in global gene regulation of enteric bacteria. It is known
      that the expression of a variety of genes is repressed by H-NS, and mutations in
      hns result in various phenotypes, but the role of H-NS in the drug resistance of
      Escherichia coli has not been known. Here we present data showing that H-NS
      contributes to multidrug resistance by regulating the expression of multidrug
      exporter genes. Deletion of the hns gene from the DeltaacrAB mutant increased
      levels of resistance against antibiotics, antiseptics, dyes, and detergents.
      Decreased accumulation of ethidium bromide and rhodamine 6G in the hns mutant
      compared to that in the parental strain was observed, suggesting the increased
      expression of some drug exporter(s) in this mutant. The increased drug resistance
      and decreased drug accumulation caused by the hns deletion were completely
      suppressed by deletion of the multifunctional outer membrane channel gene tolC.
      At least eight drug exporter systems require TolC for their functions. Among
      these, increased expression of acrEF, mdtEF, and emrKY was observed in the
      Deltahns strain by quantitative real-time reverse transcription-PCR analysis. The
      Deltahns-mediated multidrug resistance pattern is quite similar to that caused by
      overproduction of the AcrEF exporter. Deletion of the acrEF gene greatly
      suppressed the level of Deltahns-mediated multidrug resistance. However, this
      strain still retained resistance to some compounds. The remainder of the
      multidrug resistance pattern was similar to that conferred by overproduction of
      the MdtEF exporter. Double deletion of the mdtEF and acrEF genes completely
      suppressed Deltahns-mediated multidrug resistance, indicating that Deltahns
      mediated multidrug resistance is due to derepression of the acrEF and mdtEF drug
      exporter genes.

PMID- 14973024
TI  - Expression of cholera toxin under non-AKI conditions in Vibrio cholerae El Tor
      induced by increasing the exposed surface of cultures.
AB  - The regulatory systems controlling expression of the ctxAB genes encoding cholera
      toxin (CT) in the classical and El Tor biotypes of pathogenic Vibrio cholerae
      have been characterized and found to be almost identical. Notwithstanding this,
      special in vitro conditions, called AKI conditions, are required for El Tor
      bacteria to produce CT. The AKI conditions involve biphasic cultures. In phase 1
      the organism is grown in a still tube for 4 h. In phase 2 the medium is poured
      into a flask to continue growth with shaking. Virtually no expression of CT
      occurs if this protocol is not followed. Here we demonstrated that CT expression
      takes place in single-phase still cultures if the volume-to-surface-area ratio is
      decreased, both under air and under an inert atmosphere. The expression of key
      genes involved in the regulation of CT production was analyzed, and we found that
      the expression pattern closely resembles the in vivo expression pattern.

PMID- 14973025
TI  - TeiR, a LuxR-type transcription factor required for testosterone degradation in
      Comamonas testosteroni.
AB  - We have identified a new steroid-inducible gene (designated teiR [testosterone
      inducible regulator]) in Comamonas testosteroni that is required for testosterone
      degradation. Nucleotide sequence analysis of teiR predicts a 391-amino-acid
      protein which shows homology between residues 327 and 380 (C-terminal domain) to
      the LuxR helix-turn-helix DNA binding domain and between residues 192 and 227 to
      the PAS sensor domain. This domain distribution resembles that described for
      TraR, a specific transcriptional regulator involved in quorum sensing in
      Agrobacterium tumefaciens. Analysis of the gene expression indicated that teiR is
      tightly controlled at the transcriptional level by the presence of testosterone
      in the culture medium. A teiR-disrupted mutant strain was completely unable to
      use testosterone as the sole carbon and energy source. In addition, the
      expression of several steroid-inducible genes was abolished in this mutant.
      Northern blot assays revealed that teiR is required for full expression of sip48
      beta-HSD gene mRNA (encoding a steroid-inducible protein of 48 kDa and 3beta
      17beta-hydroxysteroid dehydrogenase) and also of other steroid degradation genes,
      including those encoding 3alpha-hydroxysteroid dehydrogenase, Delta(5)-3
      ketoisomerase, 3-oxo-steroid Delta(1)-dehydrogenase, and 3-oxo-steroid Delta(4)
      (5alpha)-dehydrogenase enzymes. Moreover, when teiR was provided to the teiR
      disrupted strain in trans, the transcription level of these genes was restored.
      These results indicate that TeiR positively regulates the transcription of genes
      involved in the initial enzymatic steps of steroid degradation in C.
      testosteroni.

PMID- 14973026
TI  - Transcriptional regulation of genes encoding arabinan-degrading enzymes in
      Bacillus subtilis.
AB  - Bacillus subtilis produces hemicellulases capable of releasing arabinosyl
      oligomers and arabinose from plant cell walls. In this work, we characterize the
      transcriptional regulation of three genes encoding arabinan-degrading enzymes
      that are clustered with genes encoding enzymes that further catabolize arabinose.
      The abfA gene comprised in the metabolic operon araABDLMNPQ-abfA and the xsa gene
      located 23 kb downstream most probably encode alpha-L-arabinofuranosidases (EC
      3.2.1.55). Here, we show that the abnA gene, positioned immediately upstream from
      the metabolic operon, encodes an endo-alpha-1,5-arabinanase (EC 3.2.1.99).
      Furthermore, by in vivo RNA studies, we inferred that abnA and xsa are
      monocistronic and are transcribed from sigma(A)-like promoters. Transcriptional
      fusion analysis revealed that the expression of the three arabinases is induced
      by arabinose and arabinan and is repressed by glucose. The levels of induction by
      arabinose and arabinan are higher during early postexponential growth, suggesting
      a temporal regulation. Moreover, the induction mechanism of these genes is
      mediated through negative control by the key regulator of arabinose metabolism,
      AraR. Thus, we analyzed AraR-DNA interactions by in vitro quantitative DNase I
      footprinting and in vivo analysis of single-base-pair substitutions within the
      promoter regions of xsa and abnA. The results indicate that transcriptional
      repression of the abfA and xsa genes is achieved by a tightly controlled
      mechanism but that the regulation of abnA is more flexible. We suggest that the
      expression of genes encoding extracellular degrading enzymes of arabinose
      containing polysaccharides, transport systems, and intracellular enzymes involved
      in further catabolism is regulated by a coordinate mechanism triggered by
      arabinose via AraR.

PMID- 14973027
TI  - eBURST: inferring patterns of evolutionary descent among clusters of related
      bacterial genotypes from multilocus sequence typing data.
AB  - The introduction of multilocus sequence typing (MLST) for the precise
      characterization of isolates of bacterial pathogens has had a marked impact on
      both routine epidemiological surveillance and microbial population biology. In
      both fields, a key prerequisite for exploiting this resource is the ability to
      discern the relatedness and patterns of evolutionary descent among isolates with
      similar genotypes. Traditional clustering techniques, such as dendrograms,
      provide a very poor representation of recent evolutionary events, as they attempt
      to reconstruct relationships in the absence of a realistic model of the way in
      which bacterial clones emerge and diversify to form clonal complexes. An
      increasingly popular approach, called BURST, has been used as an alternative, but
      present implementations are unable to cope with very large data sets and offer
      crude graphical outputs. Here we present a new implementation of this algorithm,
      eBURST, which divides an MLST data set of any size into groups of related
      isolates and clonal complexes, predicts the founding (ancestral) genotype of each
      clonal complex, and computes the bootstrap support for the assignment. The most
      parsimonious patterns of descent of all isolates in each clonal complex from the
      predicted founder(s) are then displayed. The advantages of eBURST for exploring
      patterns of evolutionary descent are demonstrated with a number of examples,
      including the simple Spain(23F)-1 clonal complex of Streptococcus pneumoniae,
      "population snapshots" of the entire S. pneumoniae and Staphylococcus aureus MLST
      databases, and the more complicated clonal complexes observed for Campylobacter
      jejuni and Neisseria meningitidis.

PMID- 14973028
TI  - In vivo effect of NusB and NusG on rRNA transcription antitermination.
AB  - Similarities between lambda and rRNA transcription antitermination have led to
      suggestions that they involve the same Nus factors. However, direct in vivo
      confirmation that rRNA antitermination requires all of the lambda Nus factors is
      lacking. We have therefore analyzed the in vivo role of NusB and NusG in rRNA
      transcription antitermination and have established that both are essential for
      it. We used a plasmid test system in which reporter gene mRNA was measured to
      monitor rRNA antiterminator-dependent bypass of a Rho-dependent terminator. A
      comparison of terminator read-through in a wild-type Escherichia coli strain and
      that in a nusB::IS10 mutant strain determined the requirement for NusB. In the
      absence of NusB, antiterminator-dependent terminator read-through was not
      detected, showing that NusB is necessary for rRNA transcription antitermination.
      The requirement for NusG was determined by comparing rRNA antiterminator
      dependent terminator read-through in a strain overexpressing NusG with that in a
      strain depleted of NusG. In NusG-depleted cells, termination levels were
      unchanged in the presence or absence of the antiterminator, demonstrating that
      NusG, like NusB, is necessary for rRNA transcription antitermination. These
      results imply that NusB and NusG are likely to be part of an RNA-protein complex
      formed with RNA polymerase during transcription of the rRNA antiterminator
      sequences that is required for rRNA antiterminator-dependent terminator read
      through.

PMID- 14973029
TI  - Studies of the interaction of Escherichia coli YjeQ with the ribosome in vitro.
AB  - Escherichia coli YjeQ represents a conserved group of bacteria-specific
      nucleotide-binding proteins of unknown physiological function that have been
      shown to be essential to the growth of E. coli and Bacillus subtilis. The protein
      has previously been characterized as possessing a slow steady-state GTP
      hydrolysis activity (8 h(-1)) (D. M. Daigle, L. Rossi, A. M. Berghuis, L.
      Aravind, E. V. Koonin, and E. D. Brown, Biochemistry 41: 11109-11117, 2002). In
      the work reported here, YjeQ from E. coli was found to copurify with ribosomes
      from cell extracts. The copy number of the protein per cell was nevertheless low
      relative to the number of ribosomes (ratio of YjeQ copies to ribosomes, 1:200).
      In vitro, recombinant YjeQ protein interacted strongly with the 30S ribosomal
      subunit, and the stringency of that interaction, revealed with salt washes, was
      highest in the presence of the nonhydrolyzable GTP analog 5'
      guanylylimidodiphosphate (GMP-PNP). Likewise, association with the 30S subunit
      resulted in a 160-fold stimulation of YjeQ GTPase activity, which reached a
      maximum with stoichiometric amounts of ribosomes. N-terminal truncation variants
      of YjeQ revealed that the predicted OB-fold region was essential for ribosome
      binding and GTPase stimulation, and they showed that an N-terminal peptide (amino
      acids 1 to 20 in YjeQ) was necessary for the GMP-PNP-dependent interaction of
      YjeQ with the 30S subunit. Taken together, these data indicate that the YjeQ
      protein participates in a guanine nucleotide-dependent interaction with the
      ribosome and implicate this conserved, essential GTPase as a novel factor in
      ribosome function.

PMID- 14973030
TI  - In silico and transcriptional analysis of carbohydrate uptake systems of
      Streptomyces coelicolor A3(2).
AB  - Streptomyces coelicolor is the prototype for the investigation of antibiotic
      producing and differentiating actinomycetes. As soil bacteria, streptomycetes can
      metabolize a wide variety of carbon sources and are hence vested with various
      specific permeases. Their activity and regulation substantially determine the
      nutritional state of the cell and, therefore, influence morphogenesis and
      antibiotic production. We have surveyed the genome of S. coelicolor A3(2) to
      provide a thorough description of the carbohydrate uptake systems. Among 81 ATP
      binding cassette (ABC) permeases that are present in the genome, we found 45 to
      encode a putative solute binding protein, an essential feature for carbohydrate
      permease function. Similarity analysis allowed the prediction of putative ABC
      systems for transport of cellobiose and cellotriose, alpha-glucosides, lactose,
      maltose, maltodextrins, ribose, sugar alcohols, xylose, and beta-xylosides. A
      novel putative bifunctional protein composed of a substrate binding and a
      membrane-spanning moiety is likely to account for ribose or ribonucleoside
      uptake. Glucose may be incorporated by a proton-driven symporter of the major
      facilitator superfamily while a putative sodium-dependent permease of the solute
      sodium symporter family may mediate uptake of galactose and a facilitator protein
      of the major intrinsic protein family may internalize glycerol. Of the predicted
      gene clusters, reverse transcriptase PCRs showed active gene expression in 8 of
      11 systems. Together with the previously surveyed permeases of the
      phosphotransferase system that accounts for the uptake of fructose and N
      acetylglucosamine, the genome of S. coelicolor encodes at least 53 potential
      carbohydrate uptake systems.

PMID- 14973031
TI  - In vivo analysis of the regulatory genes in the nystatin biosynthetic gene
      cluster of Streptomyces noursei ATCC 11455 reveals their differential control
      over antibiotic biosynthesis.
AB  - Six putative regulatory genes are located at the flank of the nystatin
      biosynthetic gene cluster in Streptomyces noursei ATCC 11455. Gene inactivation
      and complementation experiments revealed that nysRI, nysRII, nysRIII, and nysRIV
      are necessary for efficient nystatin production, whereas no significant roles
      could be demonstrated for the other two regulatory genes. To determine the in
      vivo targets for the NysR regulators, chromosomal integration vectors with the
      xylE reporter gene under the control of seven putative promoter regions upstream
      of the nystatin structural and regulatory genes were constructed. Expression
      analyses of the resulting vectors in the S. noursei wild-type strain and
      regulatory mutants revealed that the four regulators differentially affect
      certain promoters. According to these analyses, genes responsible for initiation
      of nystatin biosynthesis and antibiotic transport were the major targets for
      regulation. Data from cross-complementation experiments showed that nysR genes
      could in some cases substitute for each other, suggesting a functional hierarchy
      of the regulators and implying a cascade-like mechanism of regulation of nystatin
      biosynthesis.

PMID- 14973032
TI  - Relevance of peptide uptake systems to the physiology and virulence of
      Streptococcus agalactiae.
AB  - Streptococcus agalactiae is a major cause of invasive infections in human
      newborns. To satisfy its growth requirements, S. agalactiae takes up 9 of the 20
      proteinogenic amino acids from the environment. Defined S. agalactiae mutants in
      one or several of four putative peptide permease systems were constructed and
      tested for peptide uptake, growth in various media, and expression of virulence
      traits. Oligopeptide uptake by S. agalactiae was shown to be mediated by the ABC
      transporter OppA1-F, which possesses two substrate-binding proteins (OppA1 and
      OppA2) with overlapping substrate specificities. Dipeptides were found to be
      taken up in parallel by the oligopeptide permease OppA1-F, by the dipeptide ABC
      transporter DppA-E, and by the dipeptide symporter DpsA. Reverse transcription
      PCR analysis revealed a polycistronic organization of the genes oppA1-F and dppA
      E and a monocistronic organization of dpsA in S. agalactiae. The results of
      quantitative real-time PCR revealed a medium-dependent expression of the operons
      dppA-E and oppA1-F in S. agalactiae. Growth of S. agalactiae in human amniotic
      fluid was shown to require an intact dpsA gene, indicating an important role of
      DpsA during the infection of the amniotic cavity by S. agalactiae. Deletion of
      the oppB gene reduced the adherence of S. agalactiae to epithelial cells by 26%,
      impaired its adherence to fibrinogen and fibronectin by 42 and 33%, respectively,
      and caused a 35% reduction in expression of the fbsA gene, which encodes a
      fibrinogen-binding protein in S. agalactiae. These data indicate that the
      oligopeptide permease is involved in modulating virulence traits and virulence
      gene expression in S. agalactiae.

PMID- 14973033
TI  - Residues required for Bacillus subtilis PhoP DNA binding or RNA polymerase
      interaction: alanine scanning of PhoP effector domain transactivation loop and
      alpha helix 3.
AB  - Bacillus subtilis PhoP is a member of the OmpR family of response regulators that
      activates or represses genes of the Pho regulon upon phosphorylation by PhoR in
      response to phosphate deficiency. Because PhoP binds DNA and is a dimer in
      solution independent of its phosphorylation state, phosphorylation of PhoP may
      optimize DNA binding or the interaction with RNA polymerase. We describe alanine
      scanning mutagenesis of the PhoP alpha loop and alpha helix 3 region of PhoPC
      (Val190 to E214) and functional analysis of the mutated proteins. Eight residues
      important for DNA binding were clustered between Val202 and Arg210. Using in vivo
      and in vitro functional analyses, we identified three classes of mutated
      proteins. Class I proteins (PhoP(I206A), PhoP(R210A), PhoP(L209A), and
      PhoP(H208A)) were phosphorylation proficient and could dimerize but could not
      bind DNA or activate transcription in vivo or in vitro. Class II proteins
      (PhoP(H205A) and PhoP(V204A)) were phosphorylation proficient and could dimerize
      but could not bind DNA prior to phosphorylation. Members of this class had higher
      transcription activation in vitro than in vivo. The class III mutants,
      PhoP(V202A) and PhoP(D203A), had a reduced rate of phosphotransfer and could
      dimerize but could not bind DNA or activate transcription in vivo or in vitro.
      Seven alanine substitutions in PhoP (PhoP(V190A), PhoP(W191A), PhoP(Y193A),
      PhoP(F195A), PhoP(G197A,) PhoP(T199A), and PhoP(R200A)) that specifically
      affected transcription activation were broadly distributed throughout the
      transactivation loop extending from Val190 to as far toward the C terminus as
      Arg200. PhoP(W191A) and PhoP(R200A) could not activate transcription, while the
      other five mutant proteins showed decreased transcription activation in vivo or
      in vitro or both. The mutagenesis studies may indicate that PhoP has a long
      transactivation loop and a short alpha helix 3, more similar to OmpR than to PhoB
      of Escherichia coli.

PMID- 14973034
TI  - Chitinase B of "Microbulbifer degradans" 2-40 contains two catalytic domains with
      different chitinolytic activities.
AB  - Chitinase B of "Microbulbifer degradans" 2-40 is a modular protein that is
      predicted to contain two glycoside hydrolase family 18 (GH18) catalytic domains,
      two polyserine domains, and an acidic repeat domain. Each of the GH18 domains was
      shown to be catalytically active against chitin. Activity assays reveal that the
      amino-terminal catalytic domain (GH18(N)) releases methylumbelliferone from 4'
      methylumbelliferyl-N,N'-diacetylchitobiose 13.6-fold faster than the carboxy
      terminal catalytic domain (GH18(C)) and releases chitobiose from the nonreducing
      end of chitooligosaccharides, therefore functioning as an exochitinase. GH18(C)
      releases methylumbelliferone from 4'-methylumbelliferyl-N,N',N"
      triacetylchitotriose 2.7-fold faster than GH18(N) and cleaves
      chitooligosaccharides at multiple bonds, consistent with endochitinolytic
      activity. Each domain was maximally active from 30 to 37 degrees C and from pH
      7.2 to 8.0 and was not affected by Mg(2+), Mn(2+), Ca(2+), K(+), EDTA, EGTA, or
      1.0 M NaCl. The activity of each domain was moderately inhibited by Ni(2+),
      Sr(2+), and Cu(2+), while Hg(2+) completely abolished activity. When the specific
      activities of various recombinant portions of ChiB were calculated by using
      native chitin as a substrate, the polypeptide containing the endo-acting domain
      was twofold more active on native chitin than the other containing the exo-acting
      domain. The presence of both domains in a single reaction increased the amount of
      reducing sugars released from native chitin to 140% above the theoretical
      combined rate, indicating that the domains function cooperatively to degrade
      chitin. These data demonstrate that the GH18 domains of ChiB have different
      activities on the same substrate and function cooperatively to enhance chitin
      depolymerization.

PMID- 14973035
TI  - Capsule shields the function of short bacterial adhesins.
AB  - Bacterial surface structures such as capsules and adhesins are generally regarded
      as important virulence factors. Here we demonstrate that capsules block the
      function of the self-recognizing protein antigen 43 through physical shielding.
      The phenomenon is not restricted to Escherichia coli but can occur in other gram
      negative bacteria. Likewise, we show that other short adhesins exemplified by the
      AIDA-I protein are blocked by the presence of a capsule. The results support the
      notion that capsule polysaccharides sterically prevent receptor-target
      recognition of short bacterial adhesins. This negative interference has important
      biological consequences, such as affecting the ability of bacteria to form
      biofilms.

PMID- 14973036
TI  - The Pseudomonas putida Crc global regulator controls the expression of genes from
      several chromosomal catabolic pathways for aromatic compounds.
AB  - The Crc protein is involved in the repression of several catabolic pathways for
      the assimilation of some sugars, nitrogenated compounds, and hydrocarbons in
      Pseudomonas putida and Pseudomonas aeruginosa when other preferred carbon sources
      are present in the culture medium (catabolic repression). Crc appears to be a
      component of a signal transduction pathway modulating carbon metabolism in
      pseudomonads, although its mode of action is unknown. To better understand the
      role of Crc, the proteome profile of two otherwise isogenic P. putida strains
      containing either a wild-type or an inactivated crc allele was compared. The
      results showed that Crc is involved in the catabolic repression of the hpd and
      hmgA genes from the homogentisate pathway, one of the central catabolic pathways
      for aromatic compounds that is used to assimilate intermediates derived from the
      oxidation of phenylalanine, tyrosine, and several aromatic hydrocarbons. This led
      us to analyze whether Crc also regulates the expression of the other central
      catabolic pathways for aromatic compounds present in P. putida. It was found that
      genes required to assimilate benzoate through the catechol pathway (benA and
      catBCA) and 4-OH-benzoate through the protocatechuate pathway (pobA and pcaHG)
      are also negatively modulated by Crc. However, the pathway for phenylacetate
      appeared to be unaffected by Crc. These results expand the influence of Crc to
      pathways used to assimilate several aromatic compounds, which highlights its
      importance as a master regulator of carbon metabolism in P. putida.

PMID- 14973038
TI  - Dimerization of the RamC morphogenetic protein of Streptomyces coelicolor.
AB  - RamC is required for the formation of spore-forming cells called aerial hyphae by
      the bacterium Streptomyces coelicolor. This protein is membrane associated and
      has an amino-terminal protein kinase-like domain, but little is known about its
      mechanism of action. In this study we found that the presence of multiple copies
      of a defective allele of ramC inhibits morphogenesis in S. coelicolor, consistent
      with either titration of a target or formation of inactive RamC multimers. We
      identified a domain in RamC that is C terminal to the putative kinase domain and
      forms a dimer with a K(d) of approximately 0.1 micro M. These data suggest that
      RamC acts as a dimer in vivo.

PMID- 14973037
TI  - Differential impact of MexB mutations on substrate selectivity of the MexAB-OprM
      multidrug efflux pump of Pseudomonas aeruginosa.
AB  - The integral inner membrane resistance-nodulation-division (RND) components of
      three-component RND-membrane fusion protein-outer membrane factor multidrug
      efflux systems define the substrate selectivity of these efflux systems. To gain
      a better understanding of what regions of these proteins are important for
      substrate recognition, a plasmid-borne mexB gene encoding the RND component of
      the MexAB-OprM multidrug efflux system of Pseudomonas aeruginosa was mutagenized
      in vitro by using hydroxylamine and mutations compromising the MexB contribution
      to antibiotic resistance identified in a DeltamexB strain. Of 100 mutants that
      expressed wild-type levels of MexB and showed increased susceptibility to one or
      more of carbenicillin, chloramphenicol, nalidixic acid, and novobiocin, the mexB
      genes of a representative 46 were sequenced, and 19 unique single mutations were
      identified. While the majority of mutations occurred within the large periplasmic
      loops between transmembrane segment 1 (TMS-1) and TMS-2 and between TMS-7 and TMS
      8 of MexB, mutations were seen in the TMSs and in other periplasmic as well as
      cytoplasmic loops. By threading the MexB amino acid sequence through the crystal
      structure of the homologous RND transporter from Escherichia coli, AcrB, a three
      dimensional model of a MexB trimer was obtained and the mutations were mapped to
      it. Unexpectedly, most mutations mapped to regions of MexB predicted to be
      involved in trimerization or interaction with MexA rather than to regions
      expected to contribute to substrate recognition. Intragenic second-site
      suppressor mutations that restored the activity of the G220S mutant version of
      MexB, which was compromised for resistance to all tested MexAB-OprM antimicrobial
      substrates, were recovered and mapped to the apparently distal portion of MexB
      that is implicated in OprM interaction. As the G220S mutation likely impacted
      trimerization, it appears that either proper assembly of the MexB trimer is
      necessary for OprM interaction or OprM association with an unstable MexB trimer
      might stabilize it, thereby restoring activity.

PMID- 14973039
TI  - The switch I and II regions of MinD are required for binding and activating MinC.
AB  - MinD and MinC cooperate to form an efficient inhibitor of Z-ring formation that
      is spatially regulated by MinE. MinD activates MinC by recruiting it to the
      membrane and targeting it to a septal component. To better understand this
      activation, we have isolated loss-of-function mutations in minD and carried out
      site-directed mutagenesis. Many of these mutations block MinC-MinD interaction;
      however, they also prevent MinD self-interaction and membrane binding, suggesting
      that they affect nucleotide interaction or protein folding. Two mutations in the
      switch I region (MinD box) and one mutation in the switch II region had little
      affect on most MinD functions, such as MinD self-interaction, membrane binding,
      and MinE stimulation; however, they did eliminate MinD-MinC interaction. Two
      additional mutations in the switch II region did not affect MinC binding. Further
      study revealed that one of these allowed the MinCD complex to target to the
      septum but was still deficient in blocking division. These results indicate that
      the switch I and II regions of MinD are required for interaction with MinC but
      not MinE and that the switch II region has a role in activating MinC.

PMID- 14973040
TI  - Functionally critical elements of CooA-related CO sensors.
AB  - CooA is a heme-containing transcriptional activator that enables Rhodospirillum
      rubrum to sense and grow on CO as a sole energy source. We have identified a
      number of CooA homologs through database searches, expressed these heterologously
      in Escherichia coli, and monitored their ability to respond to CO in vivo.
      Further in vitro analysis of two CooA homologs from Azotobacter vinelandii and
      Carboxydothermus hydrogenoformans corroborated the in vivo data by revealing the
      ability of CO to bind to these hemoproteins and stimulate their binding at
      specific DNA sequences. These data, as well as the patterns of conserved residues
      in the homologs, are compared to what is already known about functionally
      important residues in the CooA protein of R. rubrum. The results identify
      critical regions of CooA and indicate features that distinguish CooAs from the
      general family of cyclic AMP receptor proteins.

PMID- 14973041
TI  - Plasmid-dependent methylotrophy in thermotolerant Bacillus methanolicus.
AB  - Bacillus methanolicus can efficiently utilize methanol as a sole carbon source
      and has an optimum growth temperature of 50 degrees C. With the exception of
      mannitol, no sugars have been reported to support rapid growth of this organism,
      which is classified as a restrictive methylotroph. Here we describe the DNA
      sequence and characterization of a 19,167-bp circular plasmid, designated pBM19,
      isolated from B. methanolicus MGA3. Sequence analysis of pBM19 demonstrated the
      presence of the methanol dehydrogenase gene, mdh, which is crucial for methanol
      consumption in this bacterium. In addition, five genes (pfk, encoding
      phosphofructokinase; rpe, encoding ribulose-5-phosphate 3-epimerase; tkt,
      encoding transketolase; glpX, encoding fructose-1,6-bisphosphatase; and fba,
      encoding fructose-1,6-bisphosphate aldolase) with deduced roles in methanol
      assimilation via the ribulose monophosphate pathway are encoded by pBM19. A
      shuttle vector, pTB1.9, harboring the pBM19 minimal replicon (repB and ori) was
      constructed and used to transform MGA3. Analysis of the resulting recombinant
      strain demonstrated that it was cured of pBM19 and was not able to grow on
      methanol. A pTB1.9 derivative harboring the complete mdh gene could not restore
      growth on methanol when it was introduced into the pBM19-cured strain, suggesting
      that additional pBM19 genes are required for consumption of this carbon source.
      Screening of 13 thermotolerant B. methanolicus wild-type strains showed that they
      all harbor plasmids similar to pBM19, and this is the first report describing
      plasmid-linked methylotrophy in any microorganism. Our findings should have an
      effect on future genetic manipulations of this organism, and they contribute to a
      new understanding of the biology of methylotrophs.

PMID- 14973042
TI  - Induction of plantaricin production in Lactobacillus plantarum NC8 after
      coculture with specific gram-positive bacteria is mediated by an autoinduction
      mechanism.
AB  - Plantaricin NC8 (PLNC8), a coculture-inducible two-peptide bacteriocin from
      Lactobacillus plantarum NC8, has recently been purified and genetically
      characterized. Analysis of an 8.1-kb NC8 DNA region downstream of the PLNC8
      operon revealed the presence of at least four operons involved in bacteriocin
      production, showing high homology to the plantaricin cluster in L. plantarum C11.
      However, we found a three-component regulatory operon involving a quorum-sensing
      mechanism. Two of these components, the induction factor (PLNC8IF) and the
      histidine kinase, are novel, while the response regulator is identical to PlnD
      from C11. Homologous expression of plNC8IF in NC8 allowed constitutive
      bacteriocin production. Heterologous expression of this gene in Lactococcus
      lactis MG1363 produced supernatants which promoted bacteriocin production in NC8.
      Reverse transcription-PCR studies indicated that cocultivation of NC8 with
      inducing cells promoted transcription of the bacteriocin and regulatory operons
      in NC8. An identical result was obtained after addition of an external source of
      PLNC8IF. We propose that the presence of specific bacteria could act as an
      environmental signal that is able to switch on bacteriocin production in L.
      plantarum NC8 via a quorum-sensing mechanism mediated by PLNC8IF.

PMID- 14973043
TI  - VpsT is a transcriptional regulator required for expression of vps biosynthesis
      genes and the development of rugose colonial morphology in Vibrio cholerae O1 El
      Tor.
AB  - Vibrio cholerae switches between smooth and rugose colonial variants. The rugose
      variant produces more vibrio polysaccharides (VPS(El Tor)) and forms well
      developed biofilms. Both phenotypes depend on expression of vps biosynthesis
      genes. We identified a positive transcriptional regulator of vps gene expression,
      VpsT, which is homologous to response regulators of two-component regulatory
      systems. Disruption of vpsT in the rugose variant yields smooth colonies,
      prevents formation of mature biofilms, and decreases vps gene expression. The
      interaction between VpsT and VpsR, a previously identified positive regulator of
      vps genes, was also investigated.

PMID- 14973044
TI  - Role of class A penicillin-binding proteins in PBP5-mediated beta-lactam
      resistance in Enterococcus faecalis.
AB  - Peptidoglycan polymerization complexes contain multimodular penicillin-binding
      proteins (PBP) of classes A and B that associate a conserved C-terminal
      transpeptidase module to an N-terminal glycosyltransferase or morphogenesis
      module, respectively. In Enterococcus faecalis, class B PBP5 mediates intrinsic
      resistance to the cephalosporin class of beta-lactam antibiotics, such as
      ceftriaxone. To identify the glycosyltransferase partner(s) of PBP5, combinations
      of deletions were introduced in all three class A PBP genes of E. faecalis JH2-2
      (ponA, pbpF, and pbpZ). Among mutants with single or double deletions, only JH2-2
      DeltaponA DeltapbpF was susceptible to ceftriaxone. Ceftriaxone resistance was
      restored by heterologous expression of pbpF from Enterococcus faecium but not by
      mgt encoding the monofunctional glycosyltransferase of Staphylococcus aureus.
      Thus, PBP5 partners essential for peptidoglycan polymerization in the presence of
      beta-lactams formed a subset of the class A PBPs of E. faecalis, and
      heterospecific complementation was observed with an ortholog from E. faecium.
      Site-directed mutagenesis of pbpF confirmed that the catalytic serine residue of
      the transpeptidase module was not required for resistance. None of the three
      class A PBP genes was essential for viability, although deletion of the three
      genes led to an increase in the generation time and to a decrease in
      peptidoglycan cross-linking. As the E. faecalis chromosome does not contain any
      additional glycosyltransferase-related genes, these observations indicate that
      glycan chain polymerization in the triple mutant is performed by a novel type of
      glycosyltransferase. The latter enzyme was not inhibited by moenomycin, since
      deletion of the three class A PBP genes led to high-level resistance to this
      glycosyltransferase inhibitor.

PMID- 14973045
TI  - Identification and mapping of self-assembling protein domains encoded by the
      Escherichia coli K-12 genome by use of lambda repressor fusions.
AB  - Self-assembling proteins and protein fragments encoded by the Escherichia coli
      genome were identified from E. coli K-12 strain MG1655. Libraries of random DNA
      fragments cloned into a series of lambda repressor fusion vectors were subjected
      to selection for immunity to infection by phage lambda. Survivors were identified
      by sequencing the ends of the inserts, and the fused protein sequence was
      inferred from the known genomic sequence. Four hundred sixty-three nonredundant
      open reading frame-encoded interacting sequence tags (ISTs) were recovered from
      sequencing 2,089 candidates. These ISTs, which range from 16 to 794 amino acids
      in length, were clustered into families of overlapping fragments, identifying
      potential homotypic interactions encoded by 232 E. coli genes. Repressor fusions
      identified ISTs from genes in every protein-based functional category, but
      membrane proteins were underrepresented. The IST-containing genes were enriched
      for regulatory proteins and for proteins that form higher-order oligomers. Forty
      eight (20.7%) homotypic proteins identified by ISTs are predicted to contain
      coiled coils. Although most of the IST-containing genes are identifiably related
      to proteins in other bacterial genomes, more than half of the ISTs do not have
      identifiable homologs in the Protein Data Bank, suggesting that they may include
      many novel structures. The data are available online at
      http://oligomers.tamu.edu/.

PMID- 14973046
TI  - Transcriptional organization and regulation of the L-idonic acid pathway (GntII
      system) in Escherichia coli.
AB  - The genetic organization of the idn genes that encode the pathway for L-idonate
      catabolism was characterized. The monocistronic idnK gene is transcribed
      divergently from the idnDOTR genes, which were shown to form an operon. The 215
      bp regulatory region between the idnK and idnD genes contains promoters in
      opposite orientation with transcription start sites that mapped to positions -26
      and -29 with respect to the start codons. The regulatory region also contains a
      single putative IdnR/GntR binding site centered between the two promoters, a CRP
      binding site upstream of idnD, and an UP element upstream of idnK. The genes of
      the L-idonate pathway were shown to be under catabolite repression control.
      Analysis of idnD- and idnK-lacZ fusions in a nonpolar idnD mutant that is unable
      to interconvert L-idonate and 5-ketogluconate indicated that either compound
      could induce the pathway. The L-idonate pathway was first characterized as a
      subsidiary pathway for D-gluconate catabolism (GntII), which is induced by D
      gluconate in a GntI (primary gluconate system) mutant. Here we showed that the
      idnK and idnD operons are induced by D-gluconate in a GntI system mutant,
      presumably by endogenous formation of 5-ketogluconate from D-gluconate. Thus, the
      regulation of the GntII system is appropriate for this pathway, which is
      primarily involved in L-idonate catabolism; the GntII system can be induced by D
      gluconate under conditions that block the GntI system.

PMID- 14973047
TI  - Statistical analyses of repeated measures in physiological research: a tutorial.
AB  - Experimental designs involving repeated measurements on experimental units are
      widely used in physiological research. Often, relatively many consecutive
      observations on each experimental unit are involved and the data may be quite
      nonlinear. Yet evidently, one of the most commonly used statistical methods for
      dealing with such data sets in physiological research is the repeated
      measurements ANOVA model. The problem herewith is that it is not well suited for
      data sets with many consecutive measurements; it does not deal with nonlinear
      features of the data, and the interpretability of the model may be low. The use
      of inappropriate statistical models increases the likelihood of drawing wrong
      conclusions. The aim of this article is to illustrate, for a reasonably typical
      repeated-measurements data set, how fundamental assumptions of the repeated
      measurements ANOVA model are inappropriate and how researchers may benefit from
      adopting different modeling approaches using a variety of different kinds of
      models. We emphasize intuitive ideas rather than mathematical rigor. We
      illustrate how such models represent alternatives that 1) can have much higher
      interpretability, 2) are more likely to meet underlying assumptions, 3) provide
      better fitted models, and 4) are readily implemented in widely distributed
      software products.

PMID- 14973048
TI  - Herceptin-geldanamycin immunoconjugates: pharmacokinetics, biodistribution, and
      enhanced antitumor activity.
AB  - The efficacy of monoclonal antibodies (mAbs) as single agents in targeted cancer
      therapy has proven to be limited. Arming mAbs with a potent toxic drug could
      enhance their activity. Here we report that conjugating geldanamycin (GA) to the
      anti-HER2 mAb Herceptin improved the activity of Herceptin. The IC(50)s of the
      immunoconjugate H-GA were 10-200-fold lower than that of Herceptin in
      antiproliferative assays, depending on the cell line. The H-GA mode of action
      involved HER2 degradation, which was partially lactacystin sensitive and thus
      proteasome dependent. The linkage between GA and Herceptin remained stable in the
      circulation, as suggested by the pharmacokinetics of Herceptin and conjugated GA,
      which were almost identical and significantly different from that of free GA.
      Tumor uptake of Herceptin and H-GA were similar (52 +/- 7 and 43 +/- 7% of the
      initial injected dose per gram tissue, respectively; P = 0.077), indicating no
      apparent damage attributable to conjugation. Therapy experiments in xenograft
      bearing mice consisted of weekly i.p. doses, 4 mg/kg for 4 months. H-GA showed a
      greater antitumor effect than Herceptin because it induced tumor regression in
      69% of the recipients compared with 7% by Herceptin alone. Median survival time
      was 145 days as opposed to 78 days, and 31% of the recipients remained tumor free
      2 months after therapy was terminated versus 0% in the Herceptin group.
      Enhancement of Herceptin activity could be of significant clinical value. In
      addition, the chemical linkage and the considerations in therapeutic regimen
      described here could be applied to other immunoconjugates for targeted therapy of
      a broad spectrum of cancers.

PMID- 14973049
TI  - Induction of therapeutic T-cell responses to subdominant tumor-associated viral
      oncogene after immunization with replication-incompetent polyepitope adenovirus
      vaccine.
AB  - The EBV-encoded latent membrane proteins (LMP1 and LMP2), which are expressed in
      various EBV-associated malignancies have been proposed as a potential target for
      CTL-based therapy. However, the precursor frequency for LMP-specific CTL is
      generally low, and immunotherapy based on these antigens is often compromised by
      the poor immunogenicity and potential threat from their oncogenic potential. Here
      we have developed a replication- incompetent adenoviral vaccine that encodes
      multiple HLA class I-restricted CTL epitopes from LMP1 and LMP2 as a polyepitope.
      Immunization with this polyepitope vaccine consistently generated strong LMP
      specific CTL responses in HLA A2/K(b) mice, which can be readily detected by both
      ex vivo and in vivo T-cell assays. Furthermore, a human CTL response to LMP
      antigens can be rapidly expanded after stimulation with this recombinant
      polyepitope vector. These expanded T cells displayed strong lysis of autologous
      target cells sensitized with LMP1 and/or LMP2 CTL epitopes. More importantly,
      this adenoviral vaccine was also successfully used to reverse the outgrowth of
      LMP1-expressing tumors in HLA A2/K(b) mice. These studies demonstrate that a
      replication-incompetent adenovirus polyepitope vaccine is an excellent tool for
      the induction of a protective CTL response directed toward multiple LMP CTL
      epitopes restricted through common HLA class I alleles prevalent in different
      ethnic groups where EBV-associated malignancies are endemic.

PMID- 14973050
TI  - Tumor stroma interactions induce chemoresistance in pancreatic ductal carcinoma
      cells involving increased secretion and paracrine effects of nitric oxide and
      interleukin-1beta.
AB  - Pancreatic ductal carcinoma is characterized by a profound chemoresistance. As we
      have shown previously, these tumor cells can develop chemoresistance by
      interleukin (IL)-1beta in an autocrine and nuclear factor-kappaB-dependent
      fashion. Because pancreatic ductal carcinoma contains many mesenchymal stromal
      cells, we further investigated how tumor-stroma interactions contribute to
      chemoresistance by using a transwell coculture model, including murine pancreatic
      fibroblasts and the chemosensitive human pancreatic carcinoma cell lines T3M4 and
      PT45-P1. If cultured with fibroblast-conditioned medium or kept in coculture with
      fibroblasts, both cell lines became much less sensitive toward treatment with
      etoposide than cells cultured under standard conditions. Furthermore, the
      secretion of IL-1beta in T3M4 and PT45-P1 cells was increased by the fibroblasts,
      and IL-1beta-receptor blockade abolished the resistance-inducing effect during
      cocultivation. This stimulated IL-1beta secretion could be attributed to nitric
      oxide (NO) released by the fibroblasts as an IL-1beta-inducing factor. Although
      both tumor cells secreted only little NO, which was in line with undetectable
      inducible nitric oxide synthase (iNOS) expression, fibroblasts exhibited
      significant iNOS expression and NO secretion that could be further induced by the
      tumor cells. Incubation of T3M4 and PT45-P1 cells with the NO donor S-Nitroso-N
      acetyl-D,L-penicillamine up-regulated IL-1beta secretion and conferred resistance
      toward etoposide-induced apoptosis. Conversely, the resistance-inducing effect of
      the fibroblasts was significantly abolished, when the specific iNOS inhibitor
      aminoguanidine was added during coculture. Immunohistochemistry on tissue
      sections from human pancreatic ductal carcinoma also revealed iNOS expression in
      stromal cells and IL-1beta expression in tumor cells, thus supporting the in
      vitro findings. These data clearly demonstrate that fibroblasts contribute to the
      development of chemoresistance in pancreatic carcinoma cells via increased
      secretion of NO, which in turn leads to an elevated release of IL-1beta by the
      tumor cells. These findings substantiate the implication of tumor-stromal
      interactions in the chemoresistance of pancreatic carcinoma.

PMID- 14973051
TI  - Vaccination-induced autoimmune vitiligo is a consequence of secondary trauma to
      the skin.
AB  - A major concern for cancer vaccines targeting self-tumor antigens is the risk of
      autoimmune sequelae. Although antitumor immunity correlates with autoimmune
      disease in some preclinical models, the mechanism(s) linking antitumor immunity
      and subsequent autoimmune pathology remain(s) to be determined. In the current
      study, we demonstrated that intradermal (i.d.) immunization with a recombinant
      adenovirus (Ad) expressing the murine melanoma antigen tyrosinase-related protein
      2 (AdmTrp-2) results in a moderate level of tumor protection against the B16F10
      murine melanoma without any vitiligo. Similar immunization with an Ad encoding
      human Trp-2 (AdhTrp-2) resulted in 50-fold greater protective immunity and
      produced vitiligo in all of the mice, suggesting that the development of
      autoimmunity may reflect the potency of the vaccine. Interestingly, delivery of
      AdhTrp-2 by i.m. injection generated protective immunity comparable with that
      seen in mice that received the vaccine by the i.d. route, but none of the
      recipients in the i.m. group developed vitiligo. The cellular and humoral
      responses in the i.m. immunized mice were greater than in the i.d. group;
      therefore, the lack of vitiligo was not caused by reduced efficacy of the
      vaccine. These results led us to hypothesize that vaccine-induced vitiligo was
      associated with local inflammatory responses. Mice immunized i.m. with AdhTrp-2
      did develop vitiligo when they subsequently were injected i.d. with either a
      control Ad vector or complete Freund's adjuvant, suggesting that vitiligo is
      initiated by some form of trauma within the skin. Our data demonstrated that
      autoimmune pathology is not an unavoidable outcome of effective cancer vaccines
      directed against self-tumor antigens.

PMID- 14973052
TI  - Spontaneous vitiligo in an animal model for human melanoma: role of tumor
      specific CD8+ T cells.
AB  - Tumor antigen-reactive T cells can be detected in a large proportion of melanoma
      patients, but their efficacy on tumor control in vivo remains unclear. On the
      other hand, vitiligo, a skin disorder characterized by patchy depigmented
      macules, may occur spontaneously or after antitumor therapies. Moreover, vitiligo
      is significantly associated with positive clinical response, but the mechanism is
      not understood. Therefore, the establishment of a relevant animal model in which
      melanoma and vitiligo spontaneously develop stepwise may be useful for better
      understanding of the parameters involved in the destruction of both benign and
      malignant melanocytes. In a previous work, we established a mouse model for
      melanoma in which MT/ret transgenic mice express the ret oncogene fused to the
      metallothionein promoter. Here we report that melanoma leads to spontaneous
      vitiligo. We further investigate, for the first time in this model, the natural
      antitumor T-cell response and evaluate the role of cellular immunity in the
      development of the disease. Interestingly, the occurrence of spontaneous tumor
      nodules in MT/ret mice with melanoma-associated vitiligo is significantly delayed
      when compared in melanoma mice without vitiligo. Moreover, a significant
      proportion of mice with melanoma-associated vitiligo resisted a challenge with
      syngeneic melanoma cells in contrast to animals without vitiligo. Our results
      confirm that vitiligo is associated with clinical benefit and further demonstrate
      the crucial role of CD8+ T cells for tumor control in melanoma-associated
      vitiligo.

PMID- 14973053
TI  - Molecular detection of noninvasive and invasive bladder tumor tissues and
      exfoliated cells by aberrant promoter methylation of laminin-5 encoding genes.
AB  - Laminin-5 (LN5) anchors epithelial cells to the underlying basement membrane, and
      it is encoded by three distinct genes: LAMA3, LAMB3, and LAMC2. To metastasize
      and grow, cancer cells must invade and destroy the basement membrane. Our
      previous work has shown that epigenetic inactivation is a major mechanism of
      silencing LN5 genes in lung cancers. We extended our methylation studies to
      resected bladder tumors (n = 128) and exfoliated cell samples (bladder washes and
      voided urine; n = 71) and correlated the data with clinicopathologic findings.
      Nonmalignant urothelium had uniform expression of LN5 genes and lacked
      methylation. The methylation frequencies for LN5 genes in tumors were 21-45%, and
      there was excellent concordance between methylation in tumors and corresponding
      exfoliated cells. Methylation of LAMA3 and LAMB3 and the methylation index were
      correlated significantly with several parameters of poor prognosis (tumor grade,
      growth pattern, muscle invasion, tumor stage, and ploidy pattern), whereas
      methylation of LAMC2 and methylation index were associated with shortened patient
      survival. Of particular interest, methylation frequencies of LAMA3 helped to
      distinguish invasive (72%) from noninvasive (12%) tumors. These results suggest
      that methylation of LN5 genes has potential clinical applications in bladder
      cancers.

PMID- 14973054
TI  - Adenoviral gene transfer of the human inducible nitric oxide synthase gene
      enhances the radiation response of human colorectal cancer associated with
      alterations in tumor vascularity.
AB  - Nitric oxide is a potent radiosensitizer of tumors, but its use clinically is
      limited by serious side effects when administered systemically. We have
      demonstrated previously that gene transfer of the inducible nitric oxide synthase
      gene (iNOS) into colorectal cancer cells enhances radiation-induced apoptosis in
      vitro. The objectives of this study were to further characterize the effects of
      iNOS gene transfer on the radiosensitivity of human colorectal cancer cells in
      vitro and tumors grown in athymic nude mice. Adenoviral gene transfer of iNOS
      (AdiNOS) into human colorectal cancer cell lines (HCT-116 and SNU-1040 cells)
      significantly enhanced the effects of radiation with sensitizing enhancement
      ratios (0.1) of 1.65 and 1.6, respectively. The radiation enhancement induced by
      iNOS was associated with increased iNOS expression and nitric oxide production
      and prevented by L-NIO, an enzymatic inhibitor of iNOS. AdiNOS treatment of HCT
      116 tumors combined with radiation (2 Gy x three fractions) led to a 3.4-fold
      greater (P < 0.005) tumor growth delay compared with radiation (RT) alone. AdiNOS
      plus RT also caused significant (P < 0.01) tumor regression with 63% of tumors
      regressing compared with only 6% of tumors treated with RT. AdiNOS plus RT
      significantly (P < or = 0.001) increased the percentage of apoptotic cells (22 +/
      4%) compared with either tumors treated with control vector plus RT (9 +/- 1%),
      AdiNOS alone (9 +/- 3%), or no treatment (2 +/- 1%). These radiosensitizing
      effects of AdiNOS occurred at low infection efficiency (4% of tumor infected),
      indicating a significant bystander effect.

PMID- 14973055
TI  - Hypoxia targeted gene therapy to increase the efficacy of tirapazamine as an
      adjuvant to radiotherapy: reversing tumor radioresistance and effecting cure.
AB  - Solid tumors are characterized by regions of hypoxia that are inherently
      resistant to both radiotherapy and some chemotherapy. To target this resistant
      population, bioreductive drugs that are preferentially toxic to tumor cells in a
      hypoxic environment are being evaluated in clinical trials; the lead compound,
      tirapazamine (TPZ), is being used in combination with cisplatin and/or with
      radiotherapy. Crucially, tumor response to TPZ is also dependent on the cellular
      complement of reductases. In particular, NADPH:cytochrome P450 reductase (P450R)
      plays a major role in the metabolic activation of TPZ. In a gene-directed enzyme
      prodrug therapy (GDEPT) approach using adenoviral delivery, we have overexpressed
      human P450R specifically within hypoxic cells in tumors, with the aim of
      harnessing hypoxia as a trigger for both enzyme expression and drug metabolism.
      The adenovirus used incorporates the hypoxia-responsive element (HRE) from the
      lactate dehydrogenase gene in a minimal SV40 promoter context upstream of the
      cDNA for P450R. In a human tumor model in which TPZ alone does not potentiate
      radiotherapeutic outcome (HT1080 fibrosarcoma), we witnessed complete tumor
      regression when tumors were virally transduced before treatment.

PMID- 14973056
TI  - In vitro and in vivo cytotoxic activities of recombinant immunotoxin 8H9(Fv)-PE38
      against breast cancer, osteosarcoma, and neuroblastoma.
AB  - The 8H9 monoclonal antibody (MAb) is highly reactive with a cell surface
      glycoprotein expressed on human breast cancers, childhood sarcomas, and
      neuroblastomas but is not reactive with the cell surface of normal human tissues.
      This specific reactivity suggests that MAb 8H9 may be useful for targeted cancer
      therapy. To explore this possibility, we generated two recombinant immunotoxins
      (ITs) using the single-chain Fv (scFv) of MAb 8H9. Initially the 8H9(scFv) cDNA
      was fused to a DNA encoding a 38-kDa truncated form of Pseudomonas exotoxin
      (PE38) to generate the IT 8H9(scFv)-PE38. The fusion gene was expressed in
      Escherichia coli, and the IT was purified to near homogeneity from inclusion
      bodies. The purified IT showed specific cytotoxicity on nine different cancer
      cell lines derived from breast cancer, osteosarcoma, and neuroblastomas, known to
      react with MAb 8H9. The cytotoxic activity was inhibited by MAb 8H9, showing the
      cytotoxic activity is specific. The antitumor activity of 8H9(scFv)-PE38 was
      evaluated in severe combined immunodeficient mice bearing MCF-7 breast cancers or
      OHS-M1 osteosarcomas. The IT showed a specific dose-dependent antitumor activity
      at 0.075 and 0.15 mg/kg. Next, a more stable disulfide-linked IT, 8H9(dsFv)-PE38,
      was constructed. It was produced in high yield (16%) and showed cytotoxic and
      antitumor activities similar to those of 8H9(scFv)-PE38. 8H9(dsFv)-PE38 was given
      to two cynomolgus monkeys at doses of 0.1 and 0.2 mg/kg i.v. QOD x 3 and was well
      tolerated. This shows that a dose that causes significant tumor regressions in
      mice is well tolerated by monkeys. These results make 8H9(dsFv)-PE38 a candidate
      for further development as a therapeutic agent for breast cancers, osteosarcomas,
      and neuroblastomas.

PMID- 14973057
TI  - Alteration in copy numbers of genes as a mechanism for acquired drug resistance.
AB  - Chemoresistance is a major obstacle for successful treatment of cancer. To
      identify regions of the genome associated with acquired resistance to therapeutic
      drugs, we conducted molecular cytogenetic analyses of 23 cancer-cell lines, each
      resistant to either camptothecin, cisplatin, etoposide (VP-16), Adriamycin, or 1
      beta-D-arabinofuranosylcytosine, although the parental tumor lines were not.
      Subtractive comparative genomic hybridization studies revealed regions of gain or
      loss in DNA-copy numbers that were characteristic of drug-resistant cell lines;
      i.e., differences from their drug-sensitive parental cell lines. Thirteen ATP
      binding cassette (ABC) transporter genes [ABCA3, ABCB1 (MDR1), ABCB6, ABCB8,
      ABCB10, ABCB11, ABCC1 (MRP1), ABCC4, ABCC9, ABCD3, ABCD4, ABCE1, and ABCF2] were
      amplified among 19 of the resistant cell lines examined. Three genes encoding
      antiapoptotic BCL-2 proteins (BCL2L2, MCL1, and BCL2L10) were also amplified and
      consequently overexpressed in three of the derivative lines. Down-regulation of
      BCL2L2 with an antisense oligonucleotide sensitized a VP-16 resistant ovarian
      cancer cell line (SKOV3/VP) to VP-16. A decrease in copy numbers of genes
      encoding deoxycytidine kinase, DNA topoisomerase I, and DNA topoisomerase II
      alpha reduced their expression levels in one cytosine arabinoside-resistant line,
      two of three camptothecin-resistant lines, and two of five VP-16-resistant cell
      lines, respectively. Our results indicated that changes in DNA-copy numbers of
      the genes mentioned can activate or down-regulate them in drug-resistant cell
      lines, and that such genomic alterations might be implicated in acquired
      chemoresistance.

PMID- 14973058
TI  - Translational regulation of x-linked inhibitor of apoptosis protein by
      interleukin-6: a novel mechanism of tumor cell survival.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine with diverse biological effects.
      IL-6 has been implicated in autocrine signaling pathways promoting tumor
      progression and chemoresistance in some human tumors. However, the mechanisms by
      which IL-6 modulates these responses are unknown. Aberrant apoptosis has been
      implicated as a fundamental mechanism of chemotherapeutic resistance. Thus, we
      investigated whether IL-6 alters the expression of apoptosis regulatory proteins
      as a mechanism of drug resistance. We provide evidence that IL-6 rapidly
      phosphorylates the translation initiation factor eukaryotic initiation factor-4E
      and triggers antiapoptotic responses in cholangiocarcinoma cells. Reduction of
      cellular eukaryotic initiation factor-4E by RNA interference decreases IL-6
      induced effects on cytotoxic drug-induced caspase activation and apoptosis.
      Furthermore, IL-6 increases expression of the endogenous X-linked inhibitor of
      apoptosis protein expression by translation at an internal ribosome entry site.
      Our findings that IL-6 translationally regulates X-linked inhibitor of apoptosis
      protein expression reveal a novel mechanism by which IL-6 mediates tumor cell
      survival that may be targeted therapeutically to decrease tumor progression and
      chemoresistance.

PMID- 14973059
TI  - Enhanced tumor formation in cyclin D1 x transforming growth factor beta1 double
      transgenic mice with characterization by magnetic resonance imaging.
AB  - Transgenic mice that overexpress cyclin D1 protein in the liver develop liver
      carcinomas with high penetrance. Transforming growth factor beta (TGF-beta)
      serves as either an epithelial cell growth inhibitor or a tumor promoter,
      depending on the cellular context. We interbred LFABP-cyclin D1 and Alb-TGF-beta1
      transgenic mice to produce cyclin D1/TGF-beta1 double transgenic mice and
      followed the development of liver tumors over time, characterizing cellular and
      molecular changes, tumor incidence, tumor burden, and tumor physiology
      noninvasively by magnetic resonance imaging. Compared with age-matched LFABP
      cyclin D1 single transgenic littermates, cyclin D1/TGF-beta1 mice exhibited a
      significant increase in tumor incidence. Tumor multiplicity, tumor burden, and
      tumor heterogeneity were higher in cyclin D1/TGF-beta1 mice compared with single
      transgenic littermates. Characteristics of cyclin D1/TGF-beta1 livers correlated
      with a marked induction of the peripheral periductal oval cell/stem cell
      compartment of the liver. A number of cancerous lesions from cyclin D1/TGF-beta1
      mice exhibited unique features such as ductal plate malformations and hemorrhagic
      nodules. Some lesions were contiguous with the severely diseased background liver
      and, in some cases, replaced the normal architecture of the entire organ. Cyclin
      D1/TGF-beta1 lesions, in particular, were associated with malignant features such
      as areas of vascular invasion by hepatocytes and heterogeneous hyperintensity of
      signal on T2-weighted magnetic resonance imaging. These findings demonstrate that
      TGF-beta1 promotes stem cell activation and tumor progression in the context of
      cyclin D1 overexpression in the liver.

PMID- 14973060
TI  - The tumor invasion inhibitor dihydromotuporamine C activates RHO, remodels stress
      fibers and focal adhesions, and stimulates sodium-proton exchange.
AB  - The motuporamines are macrocyclic alkaloids that inhibit tumor cell invasion by
      an, as yet, unknown mechanism. A structure-activity study recently identified
      dihydromotuporamine C (dhMotC) as a highly active and readily synthesized
      analogue. Here, we show that dhMotC causes subtle cytoskeletal alterations in
      highly invasive MDA231 breast tumor cells that include an increase in the
      thickness and number of cytoplasmic actin stress fibers. Experiments with serum
      starved Swiss 3T3 fibroblasts showed that micromolar concentrations of dhMotC
      that inhibit tumor cell invasion induce the formation of new stress fibers and
      large focal adhesion complexes that are dispersed around the entire cell
      periphery. dhMotC treatment of Swiss 3T3 cells also initiates a strong, long
      lived activation of the small GTP-binding protein Rho, and it stimulates Rho
      kinase-dependent sodium-proton exchanger activity. Liposome-mediated cell loading
      of C3 exoenzyme prevents dhMotC-mediated Rho activation and stress fiber
      formation in 3T3 cells. C3 exoenzyme loading also reestablishes elongated MDA231
      breast tumor cell invasion in the presence of dhMotC. Taken together, these
      results indicate that the ability to activate Rho is one important determinant of
      the anti-invasive activity of dhMotC.

PMID- 14973061
TI  - Induction of androgen receptor-dependent apoptosis in prostate cancer cells by
      the retinoblastoma protein.
AB  - Re-expression of a tumor suppressor in tumor cells that lack it is an effective
      way to study its functional activities. However, because tumor cells contain
      multiple mutations, tumor suppressor functions that are dependent on (an)other
      regulators are unlikely to be identified by its re-expression alone if the other
      regulators are also mutated. In this study, we show that re-expression of
      retinoblastoma (RB) together with the androgen receptor (AR) in RB- and AR
      deficient prostate cancer DU-145 cells resulted in an apoptotic activity, acting
      through the mitochondria damage-initiated caspase activation pathway, which was
      not present when RB, or the AR, was re-expressed alone. The ability of RB + AR to
      induce mitochondria damage was dependent on the proapoptotic proteins Bax and Bak
      and could be blocked by the antiapoptotic protein Bcl-x(L). Coexpressed AR did
      not detectably change RB's regulation of E2F and cell cycle progression in
      culture. On the other hand, coexpressed RB could activate the transactivation
      activity of the AR in an androgen-depleted media. Although androgen induced
      greater AR transactivation activity in this condition, it did not induce
      apoptosis in the absence of coexpressed RB. Analysis of mutants of RB and the AR
      indicated that intact pocket function of RB and the transactivation activity of
      the AR were required for RB + AR-induced apoptosis. These results provide direct
      functional data for an AR-dependent apoptosis-inducing activity of RB and
      highlight the importance of cell type-specific regulators in obtaining a more
      complete understanding of RB.

PMID- 14973062
TI  - Generation and targeting of human tumor-specific Tc1 and Th1 cells transduced
      with a lentivirus containing a chimeric immunoglobulin T-cell receptor.
AB  - CD4+ Th cells, in particular IFN-gamma-producing Th1 cells, play a critical role
      in the activation and maintenance of Tc1 cells that are essential for tumor
      eradication. Here, we report the generation of artificial tumor-specific Th1 and
      Tc1 cells from nonspecifically activated T cells using a lentiviral transduction
      system. Anti-CD3-activated T cells from healthy human donors were transduced with
      a lentivirus containing a chimeric immunoglobulin T-cell receptor gene composed
      of single-chain variable fragments derived from an anticarcinoembryonic antigen
      (CEA)-specific monoclonal antibody fused to an intracellular signaling domain
      derived from the cytoplasmic portions of membrane-bound CD28 and CD3zeta. These
      artificial tumor-specific Tc1 and Th1 cells, termed Tc1- and Th1-T bodies,
      respectively, could be targeted to CEA+ tumor cells independently of MHC
      restriction. Specifically, Tc1-T bodies demonstrated high cytotoxicity and
      produced IFN-gamma in response to CEA+ tumor cell lines but not CEA- tumors.
      Although Th1-T bodies exhibited low cytotoxicity, they secreted high levels of
      IFN-gamma and interleukin-2 in response to CEA+ tumor cells. Such CEA+ tumor
      specific activation was not observed in mock gene-transduced nonspecific Tc1 and
      Th1 cells. Moreover, Tc1- and Th1-T bodies exhibited strong antitumor activities
      against CEA+ human lung cancer cells implanted into RAG2(-/-) mice. Furthermore,
      combined therapy with Tc1- and Th1-T bodies resulted in enhanced antitumor
      activities in vivo. Taken together, our findings demonstrate that Tc1- and Th1-T
      bodies represent a promising alternative to current methods for the development
      of effective adoptive immunotherapies.

PMID- 14973063
TI  - Tumor suppressor von Hippel-Lindau (VHL) stabilization of Jade-1 protein occurs
      through plant homeodomains and is VHL mutation dependent.
AB  - The von Hippel-Lindau (VHL) gene is the major renal cancer gene in adults. The
      mechanism of renal tumor suppression by VHL protein is only partly elucidated.
      VHL loss increases expression of the hypoxia-inducible factor alpha transcription
      factors. However, clinical and biochemical data indicate that the hypoxia
      inducible factors are necessary but not sufficient for renal tumorigenesis, which
      suggests other VHL effector pathways are involved. Jade-1 protein interacts
      strongly with VHL and is most highly expressed in renal proximal tubules,
      precursor cells of renal cancer. Short-lived Jade-1 protein contains plant
      homeodomain (PHD) and candidate PEST degradation motifs and is substantially
      stabilized by VHL. The effect of VHL on Jade-1 protein abundance and relative
      protein stability was further examined in immunoblots and metabolic labeling
      experiments using two time points. VHL-Jade-1 binding was tested in
      coimmunoprecipitations. In cotransfection studies with wild-type VHL, the Jade-1
      PHD-extended PHD module, not the candidate PEST domain, was required for full VHL
      mediated stabilization. This module is also found in leukemia transcription
      factors AF10 and AF17, as well as closely related Jade-like proteins, which
      suggests all might be VHL regulated. Intriguingly, naturally occurring
      truncations and mutations of VHL affected wild-type Jade-1 binding and
      stabilization. Although the VHL beta domain was sufficient for Jade-1 binding,
      both the alpha and beta domains were required for Jade-1 stabilization. Thus,
      truncating VHL mutations, which are severe and associated with renal cancer
      development, prevented Jade-1 stabilization. Moreover, well-controlled
      cotransfection and metabolic labeling experiments revealed that VHL missense
      mutations that cause VHL disease without renal cancer, such as Tyr98His and
      Tyr112His, stabilized Jade-1 fully. In contrast, like the VHL truncations, VHL
      missense mutations commonly associated with renal cancer, such as Leu118Pro or
      Arg167Trp, did not stabilize Jade-1 fully. Therefore, loss of Jade-1 stability
      may correlate with renal cancer risk. Endogenous Jade-1 in stable renal cancer
      lines also exhibited VHL mutation-dependent regulation. As in the
      cotransfections, VHL truncations did not increase endogenous Jade-1 abundance,
      whereas the VHL missense mutations tested partially increased Jade-1 expression.
      Additional studies with non-PHD proteins indicated that Jade-1 stabilization by
      VHL is highly specific. Fibronectin was not stabilized like Jade-1 by VHL, nor
      were candidate VHL interactors from a yeast screen. Thus, protein stabilization
      likely reflects the biological activity of largely intact VHL protein on the PHD
      extended PHD module of Jade-1. Dysregulation of the VHL protein stabilization
      pathway or of Jade-1 itself may therefore contribute to VHL renal disease and
      renal cancer pathogenesis.

PMID- 14973064
TI  - Normal cells control the growth of neighboring transformed cells independent of
      gap junctional communication and SRC activity.
AB  - The growth of many types of cancer cells can be controlled by surrounding normal
      cells. However, mechanisms underlying this phenomenon have not been defined. We
      used a layered culture system to investigate how nontransformed cells suppress
      the growth of neighboring transformed cells. Direct physical contact between
      transformed and nontransformed cells was required for growth suppression of
      transformed cells in this system; communication by diffusible factors was not
      sufficient. However, significant gap junctional communication was not required,
      indicating that other intercellular junctions mediated this growth regulatory
      response. We also report that the Src kinase activity in transformed cells was
      not directly inhibited by contact with nontransformed cells. Instead,
      nontransformed cells increased the expression of serum deprivation-response
      protein and the transcription factor four and a half LIM domain 1 in tumor cells.
      In addition, these results suggest mechanisms by which normal cells may block Wnt
      signaling, inhibit insulin-like growth factor activity, and promote host
      recognition of neighboring tumor cells.

PMID- 14973065
TI  - Tumor necrosis factor-alpha-induced matrix proteolytic enzyme production and
      basement membrane remodeling by human ovarian surface epithelial cells: molecular
      basis linking ovulation and cancer risk.
AB  - The majority of cancer is of surface/cyst epithelial origin. The ovarian surface
      epithelial cells are organized by a sheet of basement membrane composed mainly of
      collagen IV and laminin, and it is believed that the basement membrane greatly
      influences the physiological properties of ovarian surface epithelial cells.
      Previous studies in our laboratories indicated that loss of the basement
      membrane, an obligated step in ovulation, is also a critical step during the
      morphological transformation and tumor initiation of the ovarian surface
      epithelium. It is speculated that the loss of basement membrane in ovarian
      surface epithelial transformation may have similar biological mechanism to the
      loss of surface epithelial basement membrane in ovulation. However, the
      mechanisms involved in the ovarian surface epithelial basement membrane removal
      during ovulation are still not completely understood. In the current study,
      cultured human ovarian surface epithelial (HOSE) cells were examined for their
      abilities to produce matrix hydrolyzing enzymes and degrade basement membrane in
      response to a number of potential local mediators in ovulation. Among the
      candidate-stimulating factors tested, tumor necrosis factor (TNF)-alpha and IL
      1beta (to a lesser extent) were found to drastically increase urokinase type
      plasminogen activator (uPA) and matrix metalloproteinase (MMP)-9 activities
      secreted from HOSE cells. MMP-2, the other major HOSE cell-secreted gelatinase,
      is constitutively produced but not regulated. As demonstrated by
      immunofluorescence staining and Western blot analysis, TNF-alpha treatment caused
      the degradation and structural reorganization of collagen IV and laminin secreted
      and deposited by HOSE cells in culture. Amiloride, an uPA inhibitor, not only
      inhibited the activity of uPA but was also able to suppress TNF-alpha-stimulated
      MMP-9 activity and prevented the TNF-alpha-stimulated remodeling of the basement
      membrane extracellular matrix, suggesting the contribution of uPA-mediated
      proteolytic cascade in this process. This study implicates the potential roles of
      TNF-alpha, uPA, and MMP-9 in ovarian surface epithelial basement membrane
      degradation and remodeling, which are processes during ovulation and may
      contribute to epithelial transformation. The findings may underscore the
      importance of TNF-alpha, uPA, and MMP-9 in ovarian surface epithelial basement
      membrane remodeling and may provide a molecular mechanism linking ovulation and
      ovarian cancer risk.

PMID- 14973066
TI  - Promotion of microsatellite instability by hepatitis C virus core protein in
      human non-neoplastic hepatocyte cells.
AB  - Hepatitis C virus proteins exert an effect on a variety of cellular functions,
      including gene expression, signal transduction, and apoptosis, and because they
      possess oncogenic potentials, they have also been suggested to play an important
      role in hepatocarcinogenesis. Although the mechanisms of hepatocarcinogenesis
      remain poorly understood, we hypothesized that the disease may arise because of a
      disturbance of the DNA repair system by hepatitis C virus proteins. To test this
      hypothesis, we developed a reproducible microsatellite instability assay system
      for mismatch-repair using human-cultured cells transducted with pCXpur retrovirus
      expression vector, in which the puromycin resistance gene was rendered out-of
      frame by insertion of a (CA)(17) dinucleotide repeat tract immediately following
      the ATG start codon. Using several human cancer cell lines known to be
      replication error positive or negative, we demonstrated that this assay system
      was useful for monitoring the propensity for mismatch-repair in the cells. This
      assay system was applicable to non-neoplastic human PH5CH8 hepatocytes, which
      could support hepatitis C virus replication. Using PH5CH8 cells, in which
      hepatitis C virus proteins were stably expressed by the retrovirus-mediated gene
      transfer, we found that the core protein promoted microsatellite instability in
      PH5CH8 cells. Interestingly, such promotion by the core protein only occurred in
      cells having the core protein belonging to genotype 1b or 2a and did not occur in
      cells having the core protein belonging to genotype 1a, 2b, or 3a. This is the
      first report to demonstrate that the core protein may disturb the DNA repair
      system.

PMID- 14973067
TI  - Small interfering double-stranded RNAs as therapeutic molecules to restore
      chemosensitivity to thymidylate synthase inhibitor compounds.
AB  - RNA interference is a post-transcriptional mechanism by which double-stranded RNA
      specifically silence expression of a corresponding gene. Small interfering double
      stranded RNA (siRNA) of 21-23 nucleotides can induce the process of RNA
      interference. Studies from our laboratory have shown that translation of
      thymidylate synthase (TS) mRNA is controlled by its own protein end-product TS in
      a negative autoregulatory manner. Disruption of this process gives rise to
      increased synthesis of TS and leads to the development of cellular drug
      resistance to TS-targeted compounds. As a strategy to inhibit TS expression at
      the mRNA level, siRNAs were designed to target nucleotides 1058-1077 on human TS
      mRNA. Transfection of TS1058 siRNA into human colon cancer RKO cells resulted in
      a dose-dependent inhibition of TS expression with an IC(50) value of 10 pM but
      had no effect on the expression of alpha-tubulin or topoisomerase I. Inhibition
      of TS expression by TS1058 was maximal at 48 h and remained suppressed for up to
      5 days. Pretreatment of RKO cells with TS1058 siRNA suppressed TS protein
      induction following exposure to raltitrexed. In addition, TS1058 restored
      chemosensitivity of the resistant RKO-HTStet cell line to various TS inhibitor
      compounds. On treatment with TS1058, IC(50) values for raltitrexed, 1843U89, and
      5-fluoro-2'-deoxyuridine decreased by approximately 15-16-fold. These studies
      suggest that TS-targeted siRNAs are effective inhibitors of TS expression and may
      have therapeutic potential by themselves or as chemosensitizers in combination
      with TS inhibitor compounds.

PMID- 14973068
TI  - Cyclooxygenase-2 promotes human cholangiocarcinoma growth: evidence for
      cyclooxygenase-2-independent mechanism in celecoxib-mediated induction of
      p21waf1/cip1 and p27kip1 and cell cycle arrest.
AB  - The expression of cyclooxygenase-2 (COX-2) is increased in human
      cholangiocarcinoma. However, the biologic function and molecular mechanisms of
      COX-2 in the control of cholangiocarcinoma cell growth have not been well
      established. This study was designed to examine the direct effect of COX-2 and
      its inhibitor celecoxib on the growth of human intrahepatic cholangiocarcinoma
      cells. Overexpression of COX-2 or treatment with prostaglandin E(2) (PGE(2))
      enhanced human cholangiocarcinoma cell growth, whereas antisense depletion of COX
      2 in these cells decreased PGE(2) production and inhibited growth. These findings
      demonstrate a direct role of COX-2-mediated PGE(2) in the growth regulation of
      human cholangiocarcinoma cells. Furthermore, the COX-2 inhibitor celecoxib
      induced a dose-dependent inhibition of cell growth, cell cycle arrest at the G(1)
      S checkpoint, and induction of cyclin-dependent kinase inhibitors p21(waf1/cip1)
      and p27(kip1). However, the high concentration of celecoxib (50 micro M) required
      for inhibition of growth, the incomplete protection of celecoxib-induced
      inhibition of cell growth by PGE(2) or COX-2 overexpression, and the fact that
      overexpression or antisense depletion of COX-2 failed to alter the level of
      p21(waf1/cip1) and p27(kip1) indicate the existence of a COX-2-independent
      mechanism in celecoxib-induced inhibition of cholangiocarcinoma cell growth.

PMID- 14973069
TI  - Resveratrol inhibits drug-induced apoptosis in human leukemia cells by creating
      an intracellular milieu nonpermissive for death execution.
AB  - Efficient apoptotic signaling is a function of a permissive intracellular milieu
      created by a decrease in the ratio of superoxide to hydrogen peroxide and
      cytosolic acidification. Resveratrol (RSV) triggers apoptosis in some systems and
      inhibits the death signal in others. In this regard, the inhibitory effect on
      hydrogen peroxide-induced apoptosis is attributed to its antioxidant property. We
      provide evidence that exposure of human leukemia cells to low concentrations of
      RSV (4-8 micro M) inhibits caspase activation, DNA fragmentation, and
      translocation of cytochrome c induced by hydrogen peroxide or anticancer drugs
      C2, vincristine, and daunorubicin. Interestingly, at these concentrations, RSV
      induces an increase in intracellular superoxide and inhibits drug-induced
      acidification. Blocking the activation of NADPH oxidase complex neutralized RSV
      induced inhibition of apoptosis. Furthermore, our results implicate intracellular
      hydrogen peroxide as a common effector mechanism in drug-induced apoptosis that
      is inhibited by preincubation with RSV. Interestingly, decreasing intracellular
      superoxide with the NADPH oxidase inhibitor diphenyliodonium reversed the
      inhibitory effect of RSV on drug-induced hydrogen peroxide production. These data
      show that low concentrations of RSV inhibit death signaling in human leukemia
      cells via NADPH oxidase-dependent elevation of intracellular superoxide that
      blocks mitochondrial hydrogen peroxide production, thereby resulting in an
      intracellular environment nonconducive for death execution.

PMID- 14973070
TI  - Identification of the apoptosis activation cascade induced in mammary carcinomas
      by energy restriction.
AB  - Energy restriction (ER) inhibits mammary carcinogenesis and results in a marked
      reduction in tumor size, effects likely to be explained by ER-mediated induction
      of apoptosis. The goal of this study was to investigate the molecular
      mechanism(s) accounting for apoptosis induction. To do this, chemically induced
      mammary carcinomas were evaluated from rats that were ad libitum fed (control),
      40% ER, or 40% ER but energy repleted for 7 days before study termination (ER
      REP); the ER-REP group permitted the determination of the reversibility of ER
      mediated effects. Cleaved products of poly(ADP-ribose) polymerase 1 were elevated
      by ER (P < 0.025) providing biochemical evidence of apoptosis induction. cDNA
      microarray analysis identified the Bcl-2, CARD, and IAP functional gene groupings
      as being involved in apoptosis induction. Consistent with the microarray data,
      the activities of caspases 9 and 3 were observed to be approximately 2-fold
      higher in carcinomas from ER rats (P < or =0.01), whereas caspase 8 activity was
      similar in carcinomas from all three of the groups. This evidence that ER-induced
      apoptosis mediated by the mitochondrial pathway was additionally supported by the
      finding that levels of Bcl-2, Bcl-xl, and XIAP protein were significantly lower
      (P < 0.01), and levels of Bax and Apaf-1 were elevated (P < 0.02) in ER
      carcinomas versus those carcinomas from control or ER-REP rats. Additional
      studies revealed that Akt phosphorylation (activation) was reduced in mammary
      carcinomas from ER rats. Thus, it appears that ER induces apoptosis in mammary
      carcinomas via a cell survival factor-dependent pathway.

PMID- 14973071
TI  - Enhanced efficacy of tumor cell vaccines transfected with secretable hsp70.
AB  - Tumor immunotherapy has exploited the ability of heat shock proteins to chaperone
      precursors of antigenic peptides to antigen-presenting cells and to activate
      efficiently an immune response against tumor-associated antigens. The most common
      strategy is based on the purification of heat shock protein-peptide complexes
      from tumor cell lines or from tumor surgical samples for in vivo administration.
      In this article, we have modified the murine-inducible hsp70 into a secreted
      protein and engineered tumor cells to secrete constitutively their antigenic
      repertoire associated with the hsp70 protein. In vitro studies showed that the
      relocalization of hsp70 from the cytoplasm to the secretory pathway did not
      modify the ability of hsp70 to interact with peptides derived either from natural
      tumor-associated antigens or model antigens, and that antigen-presenting cells
      specifically took up the secreted hsp70 and presented the chaperoned epitopes to
      T cells. In vivo studies showed that tumors secreting hsp70 displayed increased
      immunogenicity, with induction of a strong and specific CTL response. Mice
      injected with hsp70-secreting tumors showed increased survival and impaired tumor
      take compared with mice bearing parental tumors. More than 70% of mice rejected
      tumor cells secreting hsp70 through mechanisms that involve T lymphocytes and
      natural killer cells, with the induction of a memory response in the case of T
      lymphocytes. Moreover, hsp70 secretion increased the immunogenic potential of
      tumor cell vaccines.

PMID- 14973072
TI  - Human papillomavirus type 16 E6 and E7 cause polyploidy in human keratinocytes
      and up-regulation of G2-M-phase proteins.
AB  - Human papillomavirus type 16 proteins E6 and E7 have been shown to cause
      centrosome amplification and lagging chromosomes during mitosis. These
      abnormalities during mitosis can result in missegregation of the chromosomes,
      leading to chromosomal instability. Genomic instability is thought to be an
      essential part of the conversion of a normal cell to a cancer cell. We now show
      that E6 and E7 together cause polyploidy in primary human keratinocytes soon
      after these genes are introduced into the cells. Polyploidy seems to result from
      a spindle checkpoint failure arising from abrogation of the normal functions of
      p53 and retinoblastoma family members by E6 and E7, respectively. In addition, E6
      and E7 cause deregulation of cellular genes such as Plk1, Aurora-A, cdk1, and
      Nek2, which are known to control the G(2)-M-phase transition and the ordered
      progression through mitosis.

PMID- 14973073
TI  - A pivotal role of cyclic AMP-responsive element binding protein in tumor
      progression.
AB  - Tumor microenvironment controls the selection of malignant cells capable of
      surviving in stressful and hypoxic conditions. The transcription factor, cyclic
      AMP-responsive element binding (CREB) protein, activated by multiple
      extracellular signals, modulates cellular response by regulating the expression
      of a multitude of genes. Previously, we have demonstrated that two cystein
      residues, at the DNA binding domain of CREB, mediate activation of CREB-dependent
      gene expression at normoxia and hypoxia. The construction of a dominant-positive
      CREB mutant, insensitive to hypoxia cue (substitution of two cystein residues at
      position 300 and 310 with serine in the DNA binding domain) and of a dominant
      negative CREB mutant (addition of a mutation in serine(133)), enabled a direct
      assessment, in vitro and in vivo, of the role of CREB in tumor progression. In
      this work, we demonstrate both in vitro and in vivo that CREB controls
      hepatocellular carcinoma growth, supports angiogenesis, and renders resistance to
      apoptosis. Along with the identification, by DNA microarray, of the CREB
      regulated genes in normoxia and hypoxia, this work demonstrates for the first
      time that in parallel to other hypoxia responsive mechanisms, CREB plays an
      important role in hepatocellular carcinoma tumor progression.

PMID- 14973074
TI  - Molecular classifiers for gastric cancer and nonmalignant diseases of the gastric
      mucosa.
AB  - High incidence of gastric cancer-related death is mainly due to diagnosis at an
      advanced stage in addition to the lack of adequate neoadjuvant therapy. Hence,
      new tools aimed at early diagnosis would have a positive impact in the outcome of
      the disease. Using cDNA arrays having 376 genes either identified previously as
      altered in gastric tumors or known to be altered in human cancer, we determined
      expression signature of 99 tissue fragments representing normal gastric mucosa,
      gastritis, intestinal metaplasia, and adenocarcinomas. We first validated the
      array by identifying molecular markers that are associated with intestinal
      metaplasia, considered as a transition stage of gastric adenocarcinomas of the
      intestinal type as well as markers that are associated with diffuse type of
      gastric adenocarcinomas. Next, we applied Fisher's linear discriminant analysis
      in an exhaustive search of trios of genes that could be used to build classifiers
      for class distinction. Many classifiers could distinguish between normal and
      tumor samples, whereas, for the distinction of gastritis from tumor and for
      metaplasia from tumor, fewer classifiers were identified. Statistical validations
      showed that trios that discriminate between normal and tumor samples are powerful
      classifiers to distinguish between tumor and nontumor samples. More relevant, it
      was possible to identify samples of intestinal metaplasia that have expression
      signature resembling that of an adenocarcinoma and can now be used for follow-up
      of patients to determine their potential as a prognostic test for malignant
      transformation.

PMID- 14973075
TI  - 3-phosphoinositide-dependent protein kinase-1/Akt signaling represents a major
      cyclooxygenase-2-independent target for celecoxib in prostate cancer cells.
AB  - Regarding the involvement of cyclooxygenase-2 (COX-2)-independent pathways in
      celecoxib-mediated antineoplastic effects, the following two issues remain
      outstanding: identity of the non-COX-2 targets and relative contributions of COX
      2-dependent versus -independent mechanisms. We use a close celecoxib analog
      deficient in COX-2-inhibitory activity, DMC (4-[5-(2,5-dimethylphenyl)
      3(trifluoromethyl)-1H-pyrazol-1-yl]benzene-sulfonamide), to examine the premise
      that Akt signaling represents a major non-COX-2 target. Celecoxib and DMC block
      Akt activation in PC-3 cells through the inhibition of phosphoinositide-dependent
      kinase-1 (PDK-1) with IC(50) of 48 and 38 micro M, respectively. The consequent
      effect on Akt activation is more pronounced (IC(50) values of 28 and 20 micro M,
      respectively), which might be attributed to the concomitant dephosphorylation by
      protein phosphatase 2A. In serum-supplemented medium, celecoxib and DMC cause
      G(1) arrest, and at higher concentrations, they induce apoptosis with relative
      potency comparable with that in blocking Akt activation. Moreover, the effect of
      daily oral celecoxib and DMC at 100 and 200 mg/kg on established PC-3 xenograft
      tumors is assessed. Celecoxib at both doses and DMC at 100 mg/kg had marginal
      impacts. However, a correlation exists between the in vitro potency of DMC and
      its ability at 200 mg/kg to inhibit xenograft tumor growth through the inhibition
      of Akt activation. Analysis of the tumor samples indicates that a differential
      reduction in the phospho-Akt/Akt ratio was noted in celecoxib- and DMC-treated
      groups vis-a-vis the control group. Together, these data underscore the role of 3
      phosphoinositide-dependent protein kinase-1/Akt signaling in celecoxib-mediated
      in vitro antiproliferative effects in prostate cancer cells.

PMID- 14973076
TI  - Radioiodination of rhenium cyclized alpha-melanocyte-stimulating hormone
      resulting in enhanced radioactivity localization and retention in melanoma.
AB  - Radiohalogenated alpha-melanocyte-stimulating hormone (alpha-MSH) analogs were
      proposed for melanoma imaging and potential radiotherapy because alpha-MSH
      receptors are overexpressed on both mouse and human melanoma cell lines. However,
      biodistribution studies in tumor-bearing mice with radiohalogenated alpha-MSH
      peptides showed very rapid tumor radioactivity wash out due to lysosomal
      degradation of the radiohalogenated complex after internalization, which
      decreased the therapeutic efficacy significantly (R. Stein et al., Cancer Res.,
      55: 3132-3139, 1995; P. K. Garg et al., Bioconjugate Chem., 6: 493-501, 1995.).
      The melanoma-targeting metallopeptide ReO[Cys(3,4,10),D-Phe(7)]alpha-MSH(3-13)
      (ReCCMSH) was shown to possess high tumor uptake and retention properties (J.
      Chen et al., Cancer Res., 60: 5649-5658, 2000). Therefore, three peptides, Ac-Lys
      ReCCMSH(Arg(11)), Ac-D-Lys-ReCCMSH(Arg(11)), and [Nle(4),D-Phe(7)]alpha-MSH (NDP)
      (for comparison), labeled with N-succinimidyl 4-[(125)I]iodobenzoate ((125)I
      PIB), were prepared and evaluated in vitro and in vivo to develop
      radiohalogenated alpha-MSH peptide analogs with high tumor uptake, retention, and
      favorable biodistribution characteristics. In vitro cell binding and
      internalization data showed that approximately 90% of radioiodinated peptides
      were internalized at 2 h in cultured B16/F1 melanoma cells. Cellular retention
      studies showed that the receptor-bound radioiodinated linear alpha-MSH analog NDP
      was released from the cells into the medium very quickly, whereas significant
      amounts of cell-associated radioactivity remained in the cells for Ac-Lys((125)I
      3- or 4-iodobenzoate (IBA))-ReCCMSH(Arg(11)) and Ac-D-Lys((125)I-IBA)
      ReCCMSH(Arg(11)). The in vitro data clearly demonstrate that rhenium cyclization
      significantly enhanced peptide trapping in the cells, as did D-amino acid
      incorporation. The combination of these two effects resulted in a 2.9-fold
      increase in the retention of radioactivity for Ac-D-Lys((125)I-IBA)
      ReCCMSH(Arg(11)) relative to (125)I-IBA-NDP at 4 h. In vivo studies also showed
      that Ac-D-Lys((125)I-IBA)-ReCCMSH(Arg(11)) exhibited extremely high radioactivity
      accumulation and prolonged retention in the tumor. Ac-D-Lys((125)I-IBA)
      ReCCMSH(Arg(11)) and Ac-Lys((125)I-IBA)-ReCCMSH(Arg(11)) exhibited much higher
      tumor uptake at 24 h after injection compared with (125)I-IBA-NDP [7.18% injected
      dose/gram (ID/g), 4.92% ID/g, and 0.26% ID/g, respectively]. Ac-D-Lys((125)I-IBA)
      ReCCMSH(Arg(11)) also showed very fast whole body clearance and low nonspecific
      radioactivity accumulation in normal tissues compared with (125)I-IBA-NDP and Ac
      Lys((125)I-IBA)-ReCCMSH(Arg(11)). A tumor:blood ratio of 34.3 was observed for Ac
      D-Lys((125)I-IBA)-ReCCMSH(Arg(11)) at 24 h postinjection, whereas values of 4.3
      and 2.0 were observed for Ac-Lys((125)I-IBA)-ReCCMSH(Arg(11)) and (125)I-IBA-NDP,
      respectively. The biodistribution data clearly demonstrate that both rhenium
      cyclization and D-Lys incorporation enhanced the tumor localization and retention
      of the radiolabel. Therefore Ac-D-Lys-ReCCMSH(Arg(11)) is an excellent candidate
      for additional therapeutic studies.

PMID- 14973077
TI  - The Ews/Fli-1 fusion gene switches the differentiation program of neuroblastomas
      to Ewing sarcoma/peripheral primitive neuroectodermal tumors.
AB  - Neuroblastoma (NB) and the Ewing sarcoma (ES)/peripheral primitive
      neuroectodermal tumor (PNET) family are pediatric cancers derived from neural
      crest cells. Although NBs display features of the sympathetic nervous system,
      ES/PNETs express markers consistent with parasympathetic differentiation. To
      examine the control of these differentiation markers, we generated NB x ES/PNET
      somatic cell hybrids. NB-specific markers were suppressed in the hybrids, whereas
      ES/PNET-specific markers were unaffected. These results suggested that the
      Ews/Fli-1 fusion gene, resulting from a translocation unique to ES/PNETs, might
      account for the loss of NB-specific markers. To test this hypothesis, we
      generated two different NB cell lines that stably expressed the Ews/Fli-1 gene.
      We observed that heterologous expression of the Ews/Fli-1 protein led to the
      suppression of NB-specific markers and de novo expression of ES/PNET markers. To
      determine the extent of changes in differentiation, we used the Affymetrix
      GeneChip Array system to observe global transcriptional changes of genes. This
      analysis revealed that the gene expression pattern of the Ews/Fli-1-expressing NB
      cells resembled that observed in pooled ES/PNET cell lines and differed
      significantly from the NB parental cells. Therefore, we propose that Ews/Fli-1
      contributes to the etiology of ES/PNET by subverting the differentiation program
      of its neural crest precursor cell to a less differentiated and more
      proliferative state.

PMID- 14973078
TI  - Imaging tri-fusion multimodality reporter gene expression in living subjects.
AB  - Imaging reporter gene expression in living subjects with various imaging
      modalities is a rapidly accelerating area of research. Applications of these
      technologies to cancer research, gene therapy, and transgenic models are rapidly
      expanding. We report construction and testing of several triple fusion reporter
      genes compatible with bioluminescence, fluorescence and positron emission
      tomography (PET) imaging. A triple fusion reporter vector harboring a
      bioluminescence synthetic Renilla luciferase (hrl) reporter gene, a reporter gene
      encoding the monomeric red fluorescence protein (mrfp1), and a mutant herpes
      simplex virus type 1 sr39 thymidine kinase [HSV1-truncated sr39tk (ttk); a PET
      reporter gene] was found to preserve the most activity for each protein component
      and was therefore investigated in detail. After validating the activities of all
      three proteins encoded by the fusion gene in cell culture, we imaged living mice
      bearing 293T cells transiently expressing the hrl-mrfp-ttk vector by microPET and
      using a highly sensitive cooled charge-coupled device camera compatible with both
      bioluminescence and fluorescence imaging. A lentiviral vector carrying the triple
      fusion reporter gene was constructed and used to isolate stable expressers by
      fluorescence-activated cell sorting. These stable 293T cells were further used to
      show good correlation (R(2) approximately 0.74-0.85) of signal from each
      component by imaging tumor xenografts in living mice with all three modalities.
      Furthermore, metastases of a human melanoma cell line (A375M) stably expressing
      the triple fusion were imaged by microPET and optical technologies over a 40-50
      day time period in living mice. Imaging of reporter gene expression from single
      cells to living animals with the help of a single tri-fusion reporter gene will
      have the potential to accelerate translational cancer research.

PMID- 14973079
TI  - Acquisition of high-level chromosomal instability is associated with integration
      of human papillomavirus type 16 in cervical keratinocytes.
AB  - Whereas two key steps in cervical carcinogenesis are integration of high-risk
      human papillomavirus (HR-HPV) and acquisition of an unstable host genome, the
      temporal association between these events is poorly understood. Chromosomal
      instability is induced when HR-HPV E7 oncoprotein is overexpressed from
      heterologous promoters in vitro. However, it is not known whether such events
      occur at the "physiologically" elevated levels of E7 produced by deregulation of
      the homologous HR-HPV promoter after integration. Indeed, an alternative
      possibility is that integration in vivo is favored in an already unstable host
      genome. We have addressed these issues using the unique human papillomavirus
      (HPV) 16-containing cervical keratinocyte cell line W12, which was derived from a
      low-grade squamous intraepithelial lesion and thus acquired HPV16 by "natural"
      infection. Whereas W12 at low passage contains HPV16 episomes only, long-term
      culture results in the emergence of cells containing integrated HPV16 only. We
      show that integration of HPV16 in W12 is associated with 3' deletion of the E2
      transcriptional repressor, resulting in deregulation of the homologous promoter
      of the integrant and an increase in E7 protein levels. We further demonstrate
      that high-level chromosomal instability develops in W12 only after integration
      and that the forms of instability observed correlate with the physical state of
      HPV16 DNA and the level of E7 protein. Whereas intermediate E7 levels are
      associated with numerical chromosomal abnormalities, maximal levels are
      associated with both numerical and structural aberrations. HR-HPV integration is
      likely to be a critical event in cervical carcinogenesis, preceding the
      development of chromosomal abnormalities that drive malignant progression.

PMID- 14973080
TI  - Pheophorbide a is a specific probe for ABCG2 function and inhibition.
AB  - Pheophorbide a (PhA), a chlorophyll catabolite, was shown to be an ABCG2
      substrate based on Abcg2(-/-) knockout mouse studies (J. W. Jonker et al., Proc.
      Natl. Acad. Sci. USA, 99: 15649-15654, 2002). We developed a functional assay for
      ABCG2 using PhA and the ABCG2 inhibitor fumitremorgin C. In selected cell lines
      expressing high levels of P-glycoprotein, multidrug resistance-associated protein
      1, or ABCG2, PhA transport was observed only in cells expressing ABCG2.
      Fumitremorgin C-inhibitable PhA transport was found to correlate with cell
      surface ABCG2 expression as measured by the anti-ABCG2 antibody 5D3. We found
      that 100 micro M of the cyclin-dependent kinase inhibitor UCN-01 or 1 micro M of
      the P-glycoprotein inhibitor tariquidar inhibited ABCG2-mediated PhA transport.
      In 4-day cytotoxicity assays, ABCG2-mediated resistance to SN-38 and topotecan
      was abrogated in ABCG2-transfected HEK-293 cells treated with 1 micro M
      tariquidar, and ABCG2-transfected cells were 6-7-fold resistant to UCN-01. PhA is
      an ABCG2-specific substrate with potential value in measuring ABCG2 function and
      expression in clinical samples.

PMID- 14973081
TI  - Effect of isocaloric low-fat diet on prostate cancer xenograft progression to
      androgen independence.
AB  - An isocaloric low-fat diet has been shown to slow androgen-sensitive Los Angeles
      Prostate Cancer-4 (LAPC-4) tumor growth in a mouse xenograft model. LAPC-4 cells
      were injected into male severe combined immunodeficient mice. After palpable
      tumors developed, the mice were divided into three groups, high-fat intact, high
      fat castration, and low-fat castration. Tumor latency (18 versus 9 weeks; P <
      0.001) and mouse survival (20.8 +/- 1.3 versus 13 +/- 0.7 weeks; P < 0.01) were
      significantly longer in the low-fat castration versus high-fat castration group.
      Reduced dietary fat intake delayed conversion from androgen-sensitive to 
      insensitive prostate cancer and significantly prolonged survival of severe
      combined immunodeficient mice bearing LAPC-4 xenografts.

PMID- 14973082
TI  - A functional polymorphism in the EGF gene is found with increased frequency in
      glioblastoma multiforme patients and is associated with more aggressive disease.
AB  - Glioblastoma multiforme, the most aggressive form of primary brain tumor in
      adults, is nearly universally fatal, with 5-year survivals of <5% (P. Kleihues
      and W. K. Cavenee, eds., pp. 1-314, Lyon: IARC, 2000). Alterations in the
      epidermal growth factor receptor (EGFR) are common events in many glioblastoma.
      We hypothesized that a polymorphism in the 5'-untranslated region of the
      epidermal growth factor (EGF) gene, a natural ligand of the EGFR, may play a role
      in the genesis of these malignant gliomas. We find that patients with the GA or
      GG genotype have higher tumoral levels of EGF, irrespective of EGFR status, that
      they are more likely to recur after surgery, and that they have a statistically
      significant shorter overall progression-free survival than patients with the AA
      genotype. These findings suggest that a single nucleotide polymorphism in EGF may
      play a role in the formation of glioblastomas, is a useful and powerful
      prognostic marker for these patients, and may be a target for tumor therapy.

PMID- 14973083
TI  - Identification of a novel estrogen response element in the breast cancer
      resistance protein (ABCG2) gene.
AB  - The breast cancer resistance protein (BCRP) is an ATP-binding cassette half
      transporter that confers resistance to anticancer drugs such as mitoxantrone,
      anthracyclines, topotecan, and SN-38. Initial characterization of the BCRP
      promoter revealed that it is TATA-less with 5 putative Sp1 sites downstream from
      a putative CpG island and several AP1 sites (K. J. Bailey-Dell et al., Biochim.
      Biophys. Acta, 1520: 234-241, 2001). Here, we examined the sequence of the 5'
      flanking region of the BCRP gene and found a putative estrogen response element
      (ERE). We showed that estrogen enhanced the expression of BCRP mRNA in the
      estrogen receptor (ER)-positive T47D:A18 cells and PA-1 cells stably expressing
      ERalpha. In BCRP promoter-luciferase assays, sequential deletions of the BCRP
      promoter showed that the region between -243 and -115 is essential for the ER
      effect. Mutation of the ERE found within this region attenuated the estrogen
      response, whereas deletion of the site completely abrogated the estrogen effect.
      Furthermore, electrophoretic mobility shift assays revealed specific binding of
      ERalpha to the BCRP promoter through the identified ERE. Taken together, we
      provide evidence herein for a novel ERE in the BCRP promoter.

PMID- 14973084
TI  - The PhoP-PhoQ two-component regulatory system of Photorhabdus luminescens is
      essential for virulence in insects.
AB  - Photorhabdus luminescens is a symbiont of entomopathogenic nematodes. Analysis of
      the genome sequence of this organism revealed a homologue of PhoP-PhoQ, a two
      component system associated with virulence in intracellular bacterial pathogens.
      This organism was shown to respond to the availability of environmental
      magnesium. A mutant with a knockout mutation in the regulatory component of this
      system (phoP) had no obvious growth defect. It was, however, more motile and more
      sensitive to antimicrobial peptides than its wild-type parent. Remarkably, the
      mutation eliminated virulence in an insect model. No insect mortality was
      observed after injection of a large number of the phoP bacteria, while very small
      amounts of parental cells killed insect larvae in less than 48 h. At the
      molecular level, the PhoPQ system mediated Mg(2+)-dependent modifications in
      lipopolysaccharides and controlled a locus (pbgPE) required for incorporation of
      4-aminoarabinose into lipid A. Mg(2+)-regulated gene expression of pbgP1 was
      absent in the mutant and was restored when phoPQ was complemented in trans. This
      finding highlights the essential role played by PhoPQ in the virulence of an
      entomopathogen.

PMID- 14973085
TI  - Identification and functional characterization of the Lactococcus lactis rfb
      operon, required for dTDP-rhamnose Biosynthesis.
AB  - dTDP-rhamnose is an important precursor of cell wall polysaccharides and rhamnose
      containing exopolysaccharides (EPS) in Lactococcus lactis. We cloned the rfbACBD
      operon from L. lactis MG1363, which comprises four genes involved in dTDP
      rhamnose biosynthesis. When expressed in Escherichia coli, the lactococcal
      rfbACBD genes could sustain heterologous production of the Shigella flexneri O
      antigen, providing evidence of their functionality. Overproduction of the RfbAC
      proteins in L. lactis resulted in doubled dTDP-rhamnose levels, indicating that
      the endogenous RfbAC activities control the intracellular dTDP-rhamnose
      biosynthesis rate. However, RfbAC overproduction did not affect rhamnose
      containing B40-EPS production levels. A nisin-controlled conditional RfbBD mutant
      was unable to grow in media lacking the inducer nisin, indicating that the rfb
      genes have an essential role in L. lactis. Limitation of RfbBD activities
      resulted in the production of altered EPS. The monomeric sugar of the altered EPS
      consisted of glucose, galactose, and rhamnose at a molar ratio of 1:0.3:0.2,
      which is clearly different from the ratio in the native sugar. Biophysical
      analysis revealed a fourfold-greater molecular mass and a twofold-smaller radius
      of gyration for the altered EPS, indicating that these EPS are more flexible
      polymers with changed viscosifying properties. This is the first indication that
      enzyme activity at the level of central carbohydrate metabolism affects EPS
      composition.

PMID- 14973086
TI  - Seroreactivity to human papillomavirus (HPV) types 16, 18, or 31 and risk of
      subsequent HPV infection: results from a population-based study in Costa Rica.
AB  - Whether antibodies to human papillomavirus (HPV) capsids, elicited by natural
      infection, are protective is unknown. This question was addressed in a population
      based cohort of 7046 women in Costa Rica by examining the association between
      baseline seroreactivity to HPV-16, HPV-18, or HPV-31 virus-like particles and the
      risk of subsequent HPV infection at a follow-up visit 5-7 years after enrollment.
      Seropositivity to HPV-16, HPV-18, or HPV-31 was not associated with a
      statistically significant decreased risk of infection with the homologous HPV
      type [relative risk (RR) and [95% confidence interval (CI)], 0.74 (0.45-1.2), 1.5
      (0.83-2.7), and 0.94 (0.48-1.8), respectively]. Seropositivity to HPV-16 or HPV
      31 was not associated with a decreased risk of infection with HPV-16 or its
      genetically related types [RR (95% CI), 0.82 (0.61-1.1) and 0.93 (0.68-1.2),
      respectively]. Seropositivity to HPV-18 was not associated with a decreased risk
      of infection with HPV-18 or its genetically related types (RR 1.3; 95% CI 1.0
      1.8). Thus, we did not observe immunity, although a protective effect from
      natural infection cannot be excluded because of the limits of available assays
      and study designs.

PMID- 14973087
TI  - Exon 5 polymorphisms in the O6-alkylguanine DNA alkyltransferase gene and lung
      cancer risk in non-smokers exposed to second-hand smoke.
AB  - PURPOSE: The objective of the study was to examine the association of three exon
      5 variants in the O(6)-alkylguanine DNA alkyltransferase (AGT) gene involved in
      the repair of the mutagenic DNA lesion O(6)-alkylguanine formed by nitrosamines,
      with lung cancer risk in never-smokers. EXPERIMENTAL DESIGN: Exon 5 of the AGT
      gene was sequenced in genomic DNA from 136 cases and 133 hospital- or population
      based controls for whom questionnaire information on second-hand smoke and diet
      was available to determine the frequencies of the Gly(160)Arg, Ile(143)Val, and
      Lys(178)Arg variant alleles. RESULTS: No codon (160)Arg variant alleles were
      found in the study population. The codon (143)Val and (178)Arg variant alleles,
      present at allele frequencies of 0.07, showed 100% linkage. The odds ratio (OR)
      of lung cancer for these variant carriers was 2.05 [95% confidence interval (CI)
      1.03-4.07]. The risk varied between the different lung cancer pathologies with an
      increased risk for adenocarcinoma (OR 2.67, 95% CI 1.21-5.87) or small cell
      carcinoma (OR 4.83, 95% CI 0.91-25.7) but not for squamous cell carcinoma (OR
      1.07, 95% CI 0.27-4.18). Compared with individuals carrying the mutant alleles
      unexposed to second-hand smoke, the OR for exposed variant carriers was 1.95 (95%
      CI 0.53-1.15); a similar interaction, although not significative, was observed
      for low consumption of cruciferous vegetables and for green vegetables and
      tomatoes. CONCLUSIONS: These results point toward a role of AGT polymorphisms in
      lung cancer susceptibility among never-smokers, in particular among subjects
      exposed to environmental carcinogens.

PMID- 14973088
TI  - Effect of a 4-month tea intervention on oxidative DNA damage among heavy smokers:
      role of glutathione S-transferase genotypes.
AB  - Glutathione S-transferase (GST), a member of the phase II group of xenobiotic
      metabolizing enzymes, has been intensively studied at the levels of phenotype and
      genotype. The GST mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null-allele
      variant in which the entire gene is absent. The null genotype for both enzymes
      has been associated with many different types of tumors. The aim of this study
      was to determine the possible differences in increased oxidative stress
      susceptibility to smoking within the GSTM1 and GSTT1 genotypes and the impact of
      high tea drinking on this. We designed a Phase II randomized, controlled, three
      arm tea intervention trial to study the effect of high consumption (4 cups/day)
      of decaffeinated green or black tea, or water on oxidative DNA damage, as
      measured by urinary 8-hydroxydeoxyguanosine (8-OHdG), among heavy smokers over a
      4-month period and to evaluate the roles of GSTM1 and GSTT1 genotypes as effect
      modifiers. A total of 133 heavy smokers (100 females and 33 males) completed the
      intervention. GSTM1 and GSTT1 genotype statuses were determined with a PCR-based
      approach. Multiple linear regression models were used to estimate the main
      effects and interaction effect of green and black tea consumption on creatinine
      adjusted urinary 8-OHdG, with or without adjustment for potential confounders.
      Finally, we studied whether the effect of treatment varied by GSTM1 and GSTT1
      status of the individual. Although there were no differences in urinary 8-OHdG
      between the groups at baseline, the between-group 8-OHdG levels at month 4 were
      statistically significant for GSTM1-positive smokers (P = 0.05) and GSTT1
      positive smokers (P = 0.02). GSTM1-positive and GSTT1-positive smokers consuming
      green tea showed a decrease in urinary 8-OHdG levels after 4 months. Assessment
      of urinary 8-OHdG after adjustment for baseline measurements and other potential
      confounders revealed significant effect for green tea consumption (P = 0.001).
      The change from baseline was significant in both GSTM1-positive (t = -2.99; P =
      0.006) and GSTT1-positive (P = 0.004) green tea groups, but not in the GSTM1
      negative (P = 0.07) or GSTT1-negative (P = 0.909) green tea groups. Decaffeinated
      black tea consumption had no effect on urinary 8-OHdG levels among heavy smokers.
      Our data show that consumption of 4 cups of tea/day is a feasible and safe
      approach and is associated with a significant decrease in urinary 8-OHdG among
      green tea consumers after 4 months of consumption. This finding also suggests
      that green tea intervention may be effective in the subgroup of smokers who are
      GSTM1 and/or GSTT1 positive.

PMID- 14973089
TI  - Inverse association between prostate cancer and the use of calcium channel
      blockers.
AB  - Calcium channel blockers block calcium signal-mediated apoptosis. It is
      hypothesized that the use of these drugs may be associated with the development
      of cancer. This study investigated the association between daily use of calcium
      channel blockers and prostate cancer in a community-based cohort of men who
      participated in a longitudinal study of lower urinary tract symptoms. Study
      subjects were men ages 40 to 79 years by January 1, 1990, and were randomly
      selected from Olmsted County in Minnesota. At baseline, participants underwent an
      interview to determine all medications taken on a daily basis, including calcium
      channel blockers and to elicit a family history of prostate cancer. During follow
      up, all men with a histological diagnosis of prostate cancer were identified
      through patient self-report and by a review of the complete medical record. Over
      12,668 person years of follow-up, 15 (6.8%) of 220 calcium channel blocker users
      and 120 (10.5%) of 1142 nonusers developed prostate cancer (P = 0.09; odds ratio,
      0.62; 95% confidence interval, 0.36-1.10). With adjustment for age and family
      history of prostate cancer, the risk (odds ratio, 95% confidence interval) of
      prostate cancer was 0.55 (0.31-0.97) in calcium channel blocker users compared
      with nonusers. In analyses stratified by family history of prostate cancer, the
      risk of prostate cancer was 0.45 (0.23-0.88) in men without a family history and
      2.64 (0.82-8.47) in men with a family history of prostate cancer (P = 0.006).
      These findings suggest an association between prostate cancer and daily use of
      calcium channel blockers that varies by family history of prostate cancer.

PMID- 14973090
TI  - Peptic ulcer disease and the risk of bladder cancer in a prospective study of
      male health professionals.
AB  - Helicobacter pylori is a risk factor for gastric and duodenal ulcers, but gastric
      ulcers generally occur in individuals who have low acid production and diffuse
      gastritis, whereas duodenal ulcers are more likely to occur with high acid output
      and antrum-predominant gastritis. Low acid production, gastritis, and ulcer
      healing each contribute to poor antioxidant absorption, oxidative stress, and
      elevated nitrite levels in the stomach. N-Nitrosamines are known carcinogens, and
      nitrate ingestion has been related to bladder cancer risk. Consequently, we
      hypothesized that the gastric conditions associated with gastric ulcers may
      contribute to elevated bladder cancer risk. We thus examined the association
      between self-reported history of peptic ulcer disease and the risk of bladder
      cancer (414 cases) over 14 years of follow-up in the Health Professional Follow
      Up Study. Cox proportional hazards models were performed to adjust for known risk
      factors of bladder cancer. Men who reported a gastric ulcer before 1986 had a
      significantly higher risk of bladder cancer compared with those with no history
      of gastric ulcer (relative risk = 1.55, 95% confidence interval = 1.03-2.33,
      controlling for smoking and other potential confounders). No association was
      observed for duodenal ulcers (multivariate relative risk = 0.97, 95% confidence
      interval = 0.68-1.38). The ulcers in this study were based solely on self-report
      and not medical records; consequently, misclassification of ulcers may have
      occurred. Although intriguing, these findings need to be replicated.

PMID- 14973091
TI  - MTHFR polymorphisms, dietary folate intake, and breast cancer risk: results from
      the Shanghai Breast Cancer Study.
AB  - Folate plays an important role in DNA methylation, synthesis, and repair; intake
      has been associated with breast cancer. The folate-metabolizing enzyme,
      methylenetetrahydrofolate reductase (MTHFR) is polymorphic at nucleotides 677 (C-
      >T) and 1298 (A-->C), resulting in allozymes with decreased activity. We
      evaluated these two common polymorphisms and their effects on the folate intake
      and breast cancer risk association in a population-based case-control study of
      1144 breast cancer cases and 1236 controls using a PCR-RFLP-based assay. All
      subjects completed in-person interviews, which included a food frequency
      questionnaire. Unconditional logistic regression models were used to calculate
      odds ratios and their 95% confidence intervals, after adjusting for potential
      confounding factors. Cases and controls were similar in the distribution of MTHFR
      polymorphisms at codons 677 (41.4% cases and 41.8% controls carried the T allele)
      and 1298 (17.6% cases and 17.5% controls carried the C allele). An inverse
      association of breast cancer risk with folate intake was observed in all genotype
      groups, particularly among subjects with the 677TT genotype. Compared with those
      with the 677CC genotype and high folate, the adjusted odds ratios (95% confidence
      intervals) associated with low folate intake were 1.94 (1.15-3.26), 2.17 (1.34
      3.51), and 2.51 (1.37-4.60) for subjects who had CC, CT, and TT genotypes (p for
      interaction, 0.05). No modifying effect of A1298C genotypes on the association of
      folate intake with breast cancer risk was observed. Results of this study suggest
      that the MTHFR C677T polymorphisms may modify the association between dietary
      folate intake and breast cancer risk.

PMID- 14973092
TI  - Genetic polymorphisms in GSTM1, GSTP1, and GSTT1 and the risk for breast cancer:
      results from the Shanghai Breast Cancer Study and meta-analysis.
AB  - PURPOSE: We studied the relation of breast cancer to common deletion mutations in
      GSTM1 and GSTT1 and the functional Ile(105)Val polymorphism in GSTP1 in a large,
      population-based case-control study conducted in China and performed a meta
      analysis to summarize the literature. EXPERIMENTAL DESIGN: In the case-control
      study, a total of 1144 breast cancer cases and 1221 community controls were
      genotyped for GSTM1, GSTP1, and GSTT1 using PCR-based methods. Associations of
      genotypes and breast cancer were evaluated in logistic regression models. Meta
      analysis odds ratios (ORs) were estimated using a fixed effects model. RESULTS:
      In the case-control study, associations were null for GSTM1 [age-adjusted OR
      0.97, 95% confidence interval (CI): 0.82-1.14] and GSTT1 (OR 0.97, 95% CI: 0.83
      1.15). A significant increase in risk was observed among homozygotes for the
      variant Ile(105)Val polymorphism (OR 1.92, 95% CI: 1.21-3.04). No combined
      effects of GSTM1, GSTP1, and GSTT1 genotypes or interactions with potential
      effect modifiers were detected. All results were similar in pre- and
      postmenopausal women and for early versus advanced stage breast cancer. The meta
      analysis, based predominantly on Caucasian women, supported null results for the
      homozygous deletion variant in GSTM1 (summary OR 1.05; combining 19 studies) and
      GSTT1 (summary OR 1.11; 15 studies). Meta-analysis results for the homozygous
      GSTP1 variant indicated no overall association (summary OR 1.04; 10 studies),
      although results varied significantly across studies (P = 0.009). CONCLUSIONS:
      This large case-control study provides strong support for earlier studies showing
      no overall association of the GSTM1 and GSTT1 deletion polymorphisms with breast
      cancer risk. The GSTP1 variant may be relevant to breast cancer risk in Asian
      populations.

PMID- 14973093
TI  - Effects of a high-selenium yeast supplement on celecoxib plasma levels: a
      randomized phase II trial.
AB  - A combination of celecoxib and selenium was used in a randomized double-blind
      Phase II trial as a preliminary study to a multicenter Phase III colorectal
      cancer chemoprevention trial using these two agents together. The purpose of this
      trial was to determine whether high-selenium baker's yeast [(Saccharomyces
      cerevisiae) 200 microg once daily] in combination with celecoxib (400 mg once
      daily) altered the steady-state plasma concentration of celecoxib or produced
      clinically significant toxicities. Seventy-three healthy subjects (ages 40-75
      years) were recruited to the 6-week study from the general local population and
      were randomized to either the celecoxib plus selenized baker's yeast group or the
      celecoxib plus placebo group after a 2-week run in period of celecoxib only.
      Blood samples were taken at baseline (to document that there was no evidence of
      celecoxib intake), after the 2-week run-in period on celecoxib to verify steady
      state blood levels of this agent, and at end of study (4 weeks
      postrandomization). Toxicities were monitored at 2 weeks after initiation of
      celecoxib, at 4 weeks after initiation, and at the end of the study. Blood level
      concentrations of celecoxib did not differ between the two groups as determined
      by high-performance liquid chromatography analysis nor were there significant
      differences in blood chemistry values between the two groups. Subjects' self
      report of general physical toxicities was uncommon and limited to National Cancer
      Institute toxicity grade 2 or less; however, 2 female participants (3%) were
      removed from the study medications because of grade 2 edema and significant
      weight gain after 2 and 2.5 weeks of celecoxib administration. In conclusion,
      high-selenium yeast and celecoxib can be taken at the described doses with
      minimum short-term negative effects. In future Phase III chemoprevention trials
      of celecoxib, weight gain should be carefully monitored, and participants should
      be made aware of this potential side effect before study entry.

PMID- 14973094
TI  - Weight gain, body mass index, hormone replacement therapy, and postmenopausal
      breast cancer in a large prospective study.
AB  - Excess adiposity and hormone replacement therapy (HRT) are important contributors
      to postmenopausal breast cancer risk. HRT has been shown to modify the
      association between body weight and breast cancer risk, although few studies are
      sufficiently large to examine the risk of breast cancer associated with body mass
      index (BMI) and weight gain separately among current HRT users and nonusers. This
      study includes 1,934 incident breast cancer cases occurring among 62,756
      postmenopausal women in the Cancer Prevention Study-II Nutrition Cohort. Age
      adjusted incidence rates were calculated, and Cox proportional hazards models
      were used to examine the association of BMI and adult weight gain (since age 18
      years) with breast cancer risk stratified by HRT use. Total adult weight gain
      strongly predicted breast cancer risk among former and never HRT users (P for
      trend < 0.0001). Weight gain of 21-30 pounds was associated with a rate ratio of
      1.4 (95% confidence interval 1.1-1.8); rates doubled among women gaining >70
      pounds compared with women who maintained their weight within 5 pounds of their
      weight at age 18. After accounting for weight gain, neither recent BMI nor BMI at
      age 18 were independent predictors of risk. Among current HRT users, no
      association was seen between breast cancer and either BMI or weight gain. Adult
      weight gain is strongly associated with postmenopausal breast cancer only among
      non-HRT users in this study. These data illustrate the importance of examining
      breast cancer risk factors separately by HRT use; the effects of other risk
      factors may be attenuated or obscured among women taking HRT.

PMID- 14973095
TI  - Genetic variations in XRCC2 and XRCC3 are not associated with endometrial cancer
      risk.

PMID- 14973096
TI  - Serum macrophage migration inhibitory factor is not elevated in patients with
      prostate cancer.

PMID- 14973097
TI  - Evaluating organized breast cancer screening implementation: the prevention of
      late-stage disease?
AB  - The objective of our study was to evaluate organized breast cancer screening
      implementation by measuring the association between screening program enrollment
      and late-stage disease. Our setting was a health plan using mailed mammography
      reminders to women ages > or = 40. We conducted yearly cross-sectional summaries
      of mammography experience and late-stage (regional or distant Surveillance
      Epidemiology and End Results Reporting (SEER) stage) breast cancer occurrence for
      all of the health-plan women ages > or = 40 (1986-1998). We estimated the odds of
      late-stage breast cancer among health-plan and surrounding community women
      because it was too early to compare changes in mortality. We also estimated the
      odds of late-stage disease (1995-1998) associated with program enrollment and
      mammography screening among health-plan women. We found that mammography-within
      two-years increased within the health plan from 25.9% to 51.2% among women ages
      40-49 and from 32.9% to 74.7% among women ages> or = 50. Health-plan late-stage
      rates were lower than those in the surrounding community [ages 40-49: odds ratio
      (OR), 0.87; 95% confidence interval (CI), 0.77-0.99; ages 50-79: OR, 0.86; 95%
      CI, 0.80-0.92] and declined parallel to the community. Among health-plan cancer
      cases, women ages > or = 43 who were enrolled in the screening program and who
      had at least one program mammogram were less likely to have late-stage disease
      compared with the women not enrolled in the program (OR, 0.31; 95% CI, 0.16-0.61)
      but the odds of late-stage was also reduced among program-enrolled women not
      receiving program mammograms (OR, 0.45; 95% CI, 0.21-0.95). We concluded that
      enrollment in organized screening is associated with increased likelihood of
      mammography and reduced odds of late-stage breast cancer. Addressing the concerns
      of un-enrolled women and those without mammograms offers an opportunity for
      further late-stage disease reduction.

PMID- 14973098
TI  - Increased prevalence of the HFE C282Y hemochromatosis allele in women with breast
      cancer.
AB  - Individuals with the major hemochromatosis (HFE) allele C282Y and iron overload
      develop hepatocellular and some extrahepatic malignancies at increased rates. No
      association has been previously reported between the C282Y allele and breast
      cancer. We hypothesized that due to the pro-oxidant properties of iron, altered
      iron metabolism in C282Y carriers may promote breast carcinogenesis. Because 1 in
      10 Caucasians of Northern European ancestry carries this allele, any impact it
      may have on breast cancer burden is potentially great. We determined C282Y
      genotypes in 168 patients who underwent high-dose chemotherapy and blood cell
      transplantation for cancer: 41 with breast cancer and 127 with predominantly
      hematological cancers (transplant cohort). Demographic, clinical, and tumor
      characteristics were reviewed in breast cancer patients. The frequency of C282Y
      genotypes in breast cancers was compared with the frequency in nonbreast cancers,
      an outpatient sample from Tennessee (n = 169), and a published United States
      national sample. The frequency of at least one C282Y allele in breast cancers was
      higher (36.6%, 5 homozygotes/10 heterozygotes) than frequencies in Tennessee
      (12.7%, P < 0.001), the general population (12.4%, P < 0.001), and similarly
      selected nonbreast cancers (17.0%, P = 0.008). The likelihood of breast cancer in
      the transplant cohort increased with C282Y allele dose (P(trend) = 0.010). These
      results were supported by the finding in a nontransplant cohort of a higher
      frequency of C282Y mutations in Caucasian (18.4%, P = 0.039) and African-American
      (8.5%, P = 0.005) women with breast cancer than race-specific national frequency
      estimates. A high prevalence of C282Y alleles in women with breast cancer with
      and without poor risk features suggests that altered iron metabolism in C282Y
      carriers may promote the development of breast cancer and/or more aggressive
      forms of the disease.

PMID- 14973099
TI  - High-throughput detection of glutathione s-transferase polymorphic alleles in a
      pediatric cancer population.
AB  - Polymorphisms of glutathione S-transferase (GST) enzymes have been correlated
      with altered risk of several cancers, as well as altered response and toxicity
      from cancer chemotherapy. We report a low cost, highly reproducible and specific
      PCR-based high-throughput assay for genotyping different GSTs designed for use in
      large clinical trials. In comparison to an alternative genotyping method (single
      nucleotide extension), the sensitivity and specificity of the high throughput
      assay was shown to be 92 and 97%, respectively, depending on the source of
      genomic DNA. Using the high-throughput assay, we demonstrate by multivariate
      analysis an increased risk of acute lymphoblastic leukemia, glial brain tumors,
      and osteosarcoma for patients carrying nonnull alleles of GSTM1 and/or GSTT1.

PMID- 14973100
TI  - No difference in response rate to a mailed survey among prostate cancer survivors
      using conditional versus unconditional incentives.
AB  - Mailed surveys are widely used to collect epidemiological and health service data
      on cancer populations. Nonresponse can threaten the validity of surveys and
      various strategies, including the enclosure of modest incentives, are often used
      to increase response rates. A study was undertaken to determine whether response
      rate to a mailed survey differed with provision of immediate versus delayed
      incentives. A six-page mailed survey to ascertain dietary supplement use was sent
      to 1402 men who had been diagnosed with prostate cancer. Subjects were block
      randomized into two groups based on age (< or =65 years versus >65 years), race
      (white versus nonwhite), and disease status (locoregional versus distant). One
      group received a 30-min prepaid phone card concurrently with their blank survey
      (unconditional incentive), whereas the other group received the incentive only on
      receipt of their completed survey (conditional incentive). A 60% overall response
      rate was achieved, and no differences in response rates were noted between
      conditional and unconditional incentive groups (overall, as well as within
      defined age, race, and disease-defined strata). Nonwhites, however, were
      significantly less likely to respond than whites (P < 0.0001). In conclusion,
      acceptable response rates to a mailed survey can be achieved in a general
      population of cancer survivors using modest incentives. Given no differences in
      response rates using conditional versus unconditional incentives, the decision to
      provide immediate versus delayed incentives is one that should be considered on a
      study-specific basis, and a decision based primarily on cost. Other means,
      however, appear necessary to achieve acceptable response rates among minority
      group cancer survivors.

PMID- 14973101
TI  - Monitoring of intracellular enzyme kinetic characteristics of peripheral
      mononuclear cells in breast cancer patients.
AB  - A new methodology for the detection of functional response of peripheral blood
      mononuclear cells against breast cancer (BC) antigens was developed. The method
      is based on cellular enzymatic activity measurements, using a fluorogenic
      substrate. We used this method to estimate the kinetic activity of lymphocytes
      derived from cancer patients and healthy donors. The aim of the study was to
      determine a possible correlation between the basic characteristics (K(m) and
      V(max)) of biochemical enzymatic reactions in live peripheral white mononuclear
      cells and common clinical-pathological characteristics in BC patients. Our method
      shows that the enzymatic activity, upon interaction with mitogen or tumor
      antigens, of the peripheral blood cells in BC patients is different from the
      enzymatic reactions in healthy individuals. This holds true in the early stages,
      and the difference persists throughout all of the stages of the disease. This
      difference is manifested, primarily, by an increase in the K(m) values after cell
      incubation with tumor tissue. It was also demonstrated that higher K(m) values of
      tumor tissue-activated peripheral blood mononuclear cells are associated with a
      better prognostic status of the BC patients (lymph node-negative tumors, hormone
      receptor preservation, and the absence of Her-2/neu protein overexpression).
      Thus, the present methodology may serve as an additional criterion for prognosis
      and monitoring, both in BC patients, and in individuals associated with high
      cancer risk.

PMID- 14973102
TI  - BRCA1 and BRCA2 mutations in women from Shanghai China.
AB  - Little is known about the frequency of germ-line mutations in the breast cancer
      susceptibility genes BRCA1 and BRCA2 among Asian populations. We investigated the
      distribution of BRCA1 and BRCA2 germ-line mutations and polymorphisms in a cohort
      of women from Shanghai, China. Study subjects totaled 1306, and included 645
      women with breast cancer, 342 women with benign breast disease, and 319
      unaffected controls, born between 1924 and 1958, selected from women enrolled in
      a randomized trial of Breast Self-Examination in Shanghai, China. Women were
      selected without regard to family history of breast or ovarian cancer. All of the
      coding regions and exon-intron boundaries were screened. Data were analyzed with
      respect to age at diagnosis, and family history of breast and ovarian cancer. The
      prevalence of known disease-associated mutations in women with breast cancer was
      1.1% each, for BRCA1 and BRCA2. Among breast cancer cases with a family history
      of breast or ovarian cancer, 8.1% and 2.7% carried likely BRCA1 and BRCA2 disease
      associated mutations, respectively. Overall, these results suggest that inherited
      susceptibility to breast cancer due to germ-line BRCA1/2 mutations among women
      with a family history of breast cancer is comparable between women from Shanghai
      and Caucasian women of Western European descent. Most alterations observed appear
      unique to the Chinese population, suggesting a resource that will be useful for
      assessing risk among both Chinese women and United States women of Chinese
      descent.

PMID- 14973103
TI  - Bowel inflammation as measured by fecal calprotectin: a link between lifestyle
      factors and colorectal cancer risk.
AB  - The mechanisms by which the lifestyle risk factors obesity, physical inactivity,
      and low fiber intake predispose to colorectal cancer (CRC) are unclear. Chronic
      bowel inflammation predisposes to malignancy in cases of inflammatory bowel
      disease. Many lifestyle risk factors for CRC are associated with evidence of
      systemic inflammation as indicated by circulating levels of C-reactive protein
      (CRP), but it is unknown how this relates to inflammation at tissue level. Little
      is known about the degree of bowel inflammation in general population and the
      factors that affect it. Therefore, we aimed to assess the relation of levels of
      bowel inflammation in the general population and lifestyle risk factors for CRC,
      and to additionally assess whether these associations, if present, were
      attenuated by controlling for evidence of systemic inflammation. Average CRC risk
      subjects (320) of either sex aged 50-70 were recruited in South London. A stool
      sample was provided for calprotectin measurement (a marker of bowel
      inflammation), serum for CRP, and a detailed dietary and lifestyle questionnaire
      completed. There was a significant positive relationship between fecal
      calprotectin and increasing age (P = 0.002), obesity (P = 0.04), physical
      inactivity (P = 0.01), and an inverse relationship with fiber intake (P = 0.02)
      and vegetable consumption (P = 0.04). The relationship with obesity was
      attenuated by controlling for serum CRP. Fecal calprotectin levels are associated
      with lifestyle risk factors for colorectal cancer. Low-level asymptomatic bowel
      inflammation may be the link between lifestyle and the pathogenesis of CRC, and
      circulating proinflammatory cytokines may be part of the mechanism for this link.

PMID- 14973104
TI  - MTHFR C677T and A1298C polymorphisms: diet, estrogen, and risk of colon cancer.
AB  - 5,10-methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate
      metabolism, diverting metabolites toward methylation reactions or nucleotide
      synthesis. Using data from an incident case-control study (1608 cases and 1972
      controls) we investigated two polymorphisms in the MTHFR gene, C677T and A1298C,
      and their associations with risk of colon cancer. All of the combined genotypes
      were evaluated separately, and the 1298AA/677CC (wild-type/wild-type) group was
      considered the reference group. Among both men and women, the 677TT/1298AA
      (variant/wild-type) genotype was associated with a small reduction in risk [men:
      odds ratio (OR), 0.7, 95% confidence interval (CI), 0.5-1.0; women: OR, 0.8, 95%
      CI, 0.5-1.2]. However, the 677CC/1298CC (wild-type/variant) genotype was
      associated with a statistically significant lower risk among women (OR, 0.6; 95%
      CI, 0.4-0.9) but not men. When the polymorphisms were considered individually,
      for A1298C a significant risk reduction associated with the homozygous variant CC
      genotype was seen among women only (OR, 0.6; 95% CI, 0.5-0.9), and
      nonstatistically significant reduced risks were observed for the variant 677 TT
      genotypes among both men and women. Stratification by nutrient intakes showed
      inverse associations with higher intakes of folate, vitamin B(2), B(6), B(12),
      and methionine among women with the MTHFR 677CC/1298AA genotypes, but not those
      with 677TT/1298AA. We observed opposite risk trends for both MTHFR variants,
      depending on whether women used hormone-replacement therapy or not (P for
      interaction = <.01). In summary, this study supports recent findings that the
      MTHFR A1298C polymorphism may be a predictor of colon cancer risk and have
      functional relevance. The possible interaction with hormone-replacement therapy
      warrants additional investigation.

PMID- 14973105
TI  - HSD17B1 gene polymorphisms and risk of endometrial and breast cancer.
AB  - Estrogen exposure influences breast and endometrial cancer risk. The HSD17B1 gene
      produces an enzyme that catalyzes the conversion of estrone to estradiol. We
      hypothesized that genetic variations in HSD17B1 gene may alter endogenous
      estrogen levels and, thus, influence endometrial and breast cancer risk. We
      validated and genotyped polymorphisms in the HSD17B1 gene and assessed whether
      these single nucleotide polymorphisms (SNPs), or the imputed haplotypes, were
      associated with endometrial and breast cancer risk. We also assessed whether a
      priori risk factors modified the associations between HSD17B1 genotype and cancer
      risk, and whether HSD17B1 genotypes were associated with plasma estrogen levels
      among postmenopausal women not using hormone replacement therapy. Ten SNPs of
      HSD17B1 gene were validated in 30 women from the Nurses' Health Study. Using the
      expectation maximization algorithm, three common (>5% frequency) haplotypes
      accounted for 97% of the chromosomes at this locus, and seven SNPs were in
      complete linkage disequilibrium. We identified and genotyped two haplotype
      tagging SNPs (+1004C/T and +1322C/A), and genotyped an additional SNP [+1954A/G
      (Ser312Gly)] in nested case-control studies of endometrial cancer (cases = 222,
      controls = 666) and breast cancer (cases = 1007, controls = 1441) in the
      prospective Nurses' Health Study. Although no overall association by SNP or
      haplotype analysis was observed with endometrial or breast cancer risk, the
      +1954A/A genotype was associated with higher estradiol levels in lean women (P =
      0.01) and interaction between the +1954 genotype with body mass index in
      postmenopausal breast cancer (P = 0.05) was suggested. These findings suggest
      that the HSD17B1 may be associated with circulating estradiol levels and interact
      with body mass index in postmenopausal breast cancer.

PMID- 14973106
TI  - Association of SULT1A1 phenotype and genotype with prostate cancer risk in
      African-Americans and Caucasians.
AB  - Exposure to heterocyclic amines may increase prostate cancer risk. Human
      sulfotransferase 1A1 (SULT1A1) is involved in the bioactivation of some dietary
      procarcinogens, including the N-hydroxy metabolite of the food-borne heterocyclic
      amine, 2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine. This study compares a
      polymorphism in the SULT1A1 gene, SULT1A1 enzyme activity, meat consumption, and
      the risk of prostate cancer in a population based case-control study. Prostate
      cancer patients (n = 464) and control individuals (n = 459), frequency matched on
      age and ethnicity, provided informed consent, answered a survey, and provided a
      blood sample. Platelets were isolated for phenotype analysis, and DNA was
      isolated from lymphocytes for genotype determination. Meat consumption was
      assessed using a dietary questionnaire. Caucasians homozygous for the SULT1A1*1
      high activity allele were at increased risk for prostate cancer [odds ratio (OR),
      1.68; 95% confidence interval (CI), 1.05-2.68] compared with individuals
      homozygous for the low-activity allele. The association between SULT1A1 genotype
      and prostate cancer risk in African-Americans did not reach significance (OR,
      1.60; 95% CI, 0.46-5.62). When SULT1A1 activity was considered, there was a
      strong association between increased SULT1A1 activity and prostate cancer risk in
      Caucasians (OR, 3.04; 95% CI, 1.8-5.1 and OR, 4.96; 95% CI, 3.0-8.3, for the
      second and third tertiles of SULT1A1 activity, respectively) compared with
      individuals in the low enzyme activity tertile. A similar association was also
      found in African-American patients, with ORs of 6.7 and 9.6 for the second and
      third tertiles of SULT1A1 activity (95% CI, 2.1-21.3 and 2.9-31.3, respectively).
      When consumption of well-done meat was considered, there was increased risk of
      prostate cancer (OR, 1.42; 95% CI, 1.01-1.99 and OR, 1.68; 95% CI, 1.20-2.36 for
      the second and third tertiles, respectively). When SULT1A1 activity was
      stratified by tertiles of meat consumption, there was greater risk of prostate
      cancer in the highest tertile of meat consumption. These results indicate that
      variations in SULT1A1 activity contributes to prostate cancer risk and the
      magnitude of the association may differ by ethnicity and be modified by meat
      consumption.

PMID- 14973107
TI  - Plasma and dietary carotenoids, and the risk of prostate cancer: a nested case
      control study.
AB  - The association between plasma carotenoids and prostate cancer risk was
      investigated in a case-control study nested within the prospective Health
      Professionals Follow-up Study. We matched 450 incident prostate cancer cases
      diagnosed from 1993-1998 to 450 controls by age, time, month, and year of blood
      donation. Modest inverse, but not statistically significant, associations were
      observed among plasma alpha-carotene, beta-carotene, and lycopene concentrations,
      and overall risk of prostate cancer diagnosis [odds ratio (highest versus lowest
      quintile; OR), alpha-carotene: OR, 0.67 [95% confidence interval (CI), -0.40
      1.09]; beta-carotene: OR, 0.78 (95% CI, 0.48-1.25); lycopene: OR, 0.66 (95% CI,
      0.38-1.13)]. The inverse association between plasma lycopene concentrations and
      prostate cancer risk was limited to participants who were 65 years or older (OR,
      0.47; 95% CI, 0.23-0.98) and without a family history of prostate cancer (OR,
      0.48; 95% CI, 0.26-0.89). Combining, older age and a negative family history
      provided similar results (OR, 0.43; 95% CI, 0.18-1.02). Inverse associations
      between beta-carotene and prostate cancer risk were also found among younger
      participants (<65 years of age; OR, 0.36; 95% CI, 0.14-0.91; P(trend) = 0.03).
      Combining dietary intake and plasma data confirmed our results. We found a
      statistically significant inverse association between higher plasma lycopene
      concentrations and lower risk of prostate cancer, which was restricted to older
      participants and those without a family history of prostate cancer. This
      observation suggests that tomato products may exhibit more potent protection
      against sporadic prostate cancer rather than those with a stronger familial or
      hereditary component. In addition, our findings also suggest that among younger
      men, diets rich in beta-carotene may also play a protective role in prostate
      carcinogenesis.

PMID- 14973108
TI  - Prevalence of colorectal cancer screening in a large medical organization.
AB  - The primary objective of this study was to determine the prevalence of colorectal
      cancer (CRC) screening among eligible patients in a large medical practice. A
      secondary objective was to compare CRC screening rates obtained from medical
      records with physician self-reported CRC screening recommendation. We conducted a
      retrospective record review of 214 patients ages > or = 50 years of a large
      multispecialty medical organization in Houston, Texas, for receipt of fecal
      occult blood test (FOBT), flexible sigmoidoscopy (SIG), and/or colonoscopy (COL).
      We estimated prevalence using two definitions: (a) FOBT in past year or SIG in
      past 5 years or COL in past 10 years; and (b) FOBT in past year and SIG in past 5
      years or COL in past 10 years. Age, gender, race/ethnicity, family history,
      number of chronic conditions, and index visit were independent variables.
      Contingency table and logistic regression analysis were used to test for
      associations between outcomes and independent variables. Our study population was
      48% male with a mean age of 63 years (range: 53-84 years). One-quarter of the
      records showed FOBT by 3-day kit (51 of 214) and 27% by digital rectal exam (57
      of 214). SIG was recorded in 32% of records. Half (54%) of the records had
      documentation of CRC screening according to definition no. 1 and 19% according to
      definition no. 2. Screening rates from medical record review were lower than
      those derived from physician self-report. Our findings underscore the need for
      interventions to improve CRC screening in primary care settings.

PMID- 14973109
TI  - Current research promises and challenges in behavioral oncology: report from the
      American Society of Preventive Oncology annual meeting, 2002.
AB  - The Behavioral Oncology Interest Group of the American Society of Preventive
      Oncology held a Roundtable session on March 10, 2002, at the American Society of
      Preventive Oncology annual meeting in Bethesda, Maryland, to discuss the current
      state-of-the-science in behavioral approaches to cancer prevention and control
      and to delineate priorities for additional research. Four key areas were
      considered: (a) behavioral approaches to cancer genetic risk assessment and
      testing; (b) biological mechanisms of psychosocial effects on cancer; (c) the
      role of risk perceptions in cancer screening adherence; and (d) the impact of
      tailored and targeted interventions on cancer prevention and control research.
      The evidence reviewed indicates that behavioral approaches have made significant
      contributions to cancer prevention and control research. At the same time, there
      is a need to more closely link future investigations to the underlying base of
      behavioral science principles and paradigms that guide them. To successfully
      bridge the gap between the availability of effective new cancer prevention and
      control technologies and the participants they are meant to serve will require
      the development of more integrative conceptual models, the incorporation of more
      rigorous methodological designs, and more precise identification of the
      individual and group characteristics of the groups under study.

PMID- 14973110
TI  - Relative validity of a food frequency questionnaire with a meat-cooking and
      heterocyclic amine module.
AB  - The nutrient and heterocyclic amine (HCA) intake of 165 healthy participants was
      assessed using a self-administered food frequency questionnaire (FFQ), which
      included a meat-cooking practices module. A database containing the HCA [2-amino
      3,8-dimethylimadazo [4,5-f] quinoxaline (MeIQx) and 2-amino-1-methyl-6
      phenylimadazo [4,5-b] pyridine (PhIP)] composition of various types of meat,
      cooked by different methods and to varying degrees, was developed and validated
      in conjunction with this module. The relative validity of dietary and HCA intake
      estimated by the FFQ was investigated using multiple food diaries (3 sets of 4
      nonconsecutive day diaries completed over a 3-month period) as the reference
      method. Crude correlation coefficients of HCA intake assessed by the FFQ and food
      diaries were 0.43 [95% confidence interval (CI) 0.30-0.55] for MeIQx and 0.22
      (95% CI 0.07-0.36) for PhIP intake. Deattenuated correlations were 0.60 (95% CI
      0.49-0.69) and 0.36 (95% CI 0.22-0.49), respectively. Absolute MeIQx and PhIP
      intake was, however, underestimated by the FFQ (21.9 and 78.1 ng/day) compared
      with the food diaries (34.9 and 263.8 ng/day). The FFQ underestimated total red
      meat intake, the percentage of consumers, and the median intake of roast/baked
      and microwaved red meat. PhIP intake was severely underestimated by the FFQ and
      was most likely because of an underestimation of the percentage of people who
      cooked chicken using PhIP-producing cooking methods such as broiling and pan
      frying. Additionally, the FFQ overestimated the percentage of consumers of baked
      chicken, a cooking method that produces less PhIP. In conclusion, although the
      FFQ and meat module underestimated absolute MeIQx and PhIP intake, its ability to
      rank individuals according to intake was acceptable.

PMID- 14973112
TI  - Selective estrogen receptor modulators: discrimination of agonistic versus
      antagonistic activities by gene expression profiling in breast cancer cells.
AB  - Selective estrogen receptor modulators (SERMs) such as tamoxifen are effective in
      the treatment of many estrogen receptor-positive breast cancers and have also
      proven to be effective in the prevention of breast cancer in women at high risk
      for the disease. The comparative abilities of tamoxifen versus raloxifene in
      breast cancer prevention are currently being compared in the Study of Tamoxifen
      and Raloxifene trial. To better understand the actions of these compounds in
      breast cancer, we have examined their effects on the expression of approximately
      12,000 genes, using Affymetrix GeneChip microarrays, with quantitative PCR
      verification in many cases, categorizing their actions as agonist, antagonist, or
      partial agonist/antagonist. Analysis of gene stimulation and inhibition by the
      SERMs trans-hydroxytamoxifen (TOT) and raloxifene (Ral) or ICI 182,780 (ICI) and
      by estradiol (E2) in estrogen receptor-containing MCF-7 human breast cancer cells
      revealed that (a) TOT was the most E2-like of the three compounds, (b) all three
      compounds either partially or fully antagonized the action of E2 on most genes,
      with the order of antagonist activity being ICI > Ral > TOT, (c) TOT and Ral, but
      not ICI, displayed partial agonist/partial antagonist activity on a number of E2
      regulated genes, (d) several stimulatory cell cycle-related genes were down
      regulated exclusively by ICI, (e) the estrogen-like activity of Ral nearly always
      overlapped with that of TOT, indicating that Ral has little unique agonist
      activity different from that of TOT, and (f) some genes were specifically up
      regulated by TOT but not Ral, ICI, or E2. Hence, gene expression profiling can
      discern fundamental differences among SERMs and provides insight into the
      distinct biologies of TOT, Ral, and ICI in breast cancer.

PMID- 14973113
TI  - A mutant high-density lipoprotein receptor inhibits proliferation of human breast
      cancer cells.
AB  - High-density lipoprotein (HDL) stimulates the growth of many types of cells,
      including those of breast cancer. High levels of HDL are associated with an
      increased risk of breast cancer development. A scavenger receptor of the B class
      (SR-BI)/human homolog of SR-BI, CD36, and LIMPII analogous-1 (CLA-1) facilitates
      the cellular uptake of cholesterol from HDL and thus augments cell growth.
      Furthermore, HDL is also believed to have antiapoptotic effects on various cell
      types, and this feature adds to its ability to promote cell growth. These
      collaborative roles of HDL and CLA-1 prompted us to assess the function of these
      components on human breast cancer cells. In this study, we created a mutant CLA-1
      (mCLA) that lacked the COOH-terminal tail to determine its potential role in
      breast cancer cell growth. Expression of mCLA inhibited the proliferation of
      breast cancer cell line MCF-7. This inhibitory action of mCLA required the
      transcriptional factor activator protein-1 (AP-1), and the mutant receptor also
      affected the antiapoptotic features of HDL. The effect of HDL on AP-1 activation
      and [(3)H]thymidine incorporation was abrogated by wortmannin, a specific
      inhibitor of phosphoinositide 3-kinase. Furthermore, the dominant negative mutant
      of Akt abolished the ability of HDL to activate AP-1. These findings raise the
      possibility that the inhibitors of the effects of HDL may be of therapeutic value
      for breast cancer.

PMID- 14973114
TI  - Cyclooxygenase-2 is essential for HER2/neu to suppress N- (4
      hydroxyphenyl)retinamide apoptotic effects in breast cancer cells.
AB  - We reported that HER2/neu reduces the sensitivity of breast cancer cells to N-(4
      hydroxyphenyl)retinamide (4-HPR) by suppressing nitric oxide production. We show
      that HER2/neu uses Akt to induce cyclooxygenase-2 (COX-2) expression and that
      inhibition of Akt or COX-2 increases 4-HPR-induced apoptosis and nitric oxide
      production. Apoptosis induced by the 4-HPR and COX-2 inhibitor combination,
      although unaffected by an anti-HER2/neu antibody, was reversed by the COX-2
      product prostaglandin E(2), indicating that COX-2 is a major mechanism by which
      HER2/neu suppresses 4-HPR apoptosis in breast cancer cells. Combining 4-HPR with
      COX-2 inhibitors may be a novel chemopreventive strategy against HER2/neu
      overexpressing breast tumors.

PMID- 14973115
TI  - Polymorphism in the androgen receptor and mammographic density in women taking
      and not taking estrogen and progestin therapy.
AB  - There is some evidence that women with a higher number of CAG repeat lengths on
      the androgen receptor (AR) gene have increased breast cancer risk. We evaluated
      the association between AR-CAG repeat length and mammographic density, a strong
      breast cancer risk factor, in 404 African-American and Caucasian breast cancer
      patients. In postmenopausal estrogen progestin therapy users, carriers of the
      less active AR-CAG had statistically significantly higher mean percentage of
      density (41.4%) than carriers of the more active AR-CAG (25.7%; P = 0.04). Our
      results raise the question of whether the number of AR-CAG repeats predicts
      breast cancer risk in estrogen progestin therapy users.

PMID- 14973116
TI  - Association of homozygous wild-type glutathione S-transferase M1 genotype with
      increased breast cancer risk.
AB  - More than 500 studies have examined the association of the glutathione S
      transferase M1 (GSTM1) genotype with various malignancies yielding inconsistent
      results. The genotyping was based on a PCR assay that identified the GSTM1 null (
      /-) genotype but did not distinguish homozygous wild-type (+/+) and heterozygous
      (+/-) individuals. We developed an assay that allowed the definition of +/+, +/-,
      and -/- genotypes by separate identification of wild-type and null alleles, which
      were found with frequencies of 0.225 and 0.775, respectively, in Caucasian women.
      We applied the new assay to a breast cancer case-control study and identified the
      +/+ genotype in 14 (6.9%) of 202 control subjects compared with 37 (18.2%) of 203
      patients. Compared with women with the -/- genotype, the relative risk of breast
      cancer for the +/+ genotype was 2.83 (95% confidence interval, 1.45-5.59; P =
      0.002), suggesting a protective effect of the GSTM1 deletion.

PMID- 14973117
TI  - Endothelin B receptor blockade inhibits dynamics of cell interactions and
      communications in melanoma cell progression.
AB  - Phenotypic and genotypic analyses of cutaneous melanoma have identified the
      endothelin B receptor (ET(B)R) as tumor progression marker, thus representing a
      potential therapeutic target. Here, we demonstrate that activation of ET(B)R by
      endothelin-1 (ET-1) and ET-3 leads to loss of expression of the cell adhesion
      molecule E-cadherin and associated catenin proteins and gain of N-cadherin
      expression. Exposure of melanoma cells to ET-1 leads to a 60% inhibition in
      intercellular communication by inducing phosphorylation of gap junctional protein
      connexin 43. Additionally, activation of the ET(B)R pathway increases
      alpha(v)beta(3) and alpha(2)beta(1) integrin expression and matrix
      metalloproteinase (MMP)-2 and MMP-9, membrane type-1-MMP activation, and tissue
      inhibitor MMP-2 secretion. The ET(B)R pathway results into the downstream
      activation of focal adhesion kinase and extracellular signal-regulated kinase 1/2
      signaling pathways, which lead to enhanced cell proliferation, adhesion,
      migration, and MMP-dependent invasion. The small molecule A-192621, an orally
      bioavailable nonpeptide ET(B)R antagonist, significantly inhibits melanoma growth
      in nude mice. These findings demonstrate that ET-1 and ET-3 through ET(B)R
      activation trigger signaling pathways involved in events associated with
      disruption of normal host-tumor interactions and progression of cutaneous
      melanoma. Pharmacological interruption of ET(B)R signaling may represent a novel
      therapeutic strategy in the treatment of this malignancy.

PMID- 14973118
TI  - Beta-catenin up-regulates the expression of the urokinase plasminogen activator
      in human colorectal tumors.
AB  - Expression of the urokinase plasminogen activator (uPA) increases during the
      progression of colorectal tumors from adenomas to carcinomas. The highest amounts
      of uPA are found at the invasion front of carcinomas, which also displays a
      strong expression of nuclear beta-catenin and is therefore a region expressing
      beta-catenin target genes at high levels. Here we show that beta-catenin
      contributes to the transactivation of uPA. Therefore, beta-catenin might have an
      impact on the capacity of colorectal tumors for invasion and metastasis, as well
      as dormancy, which are hallmarks of cancer.

PMID- 14973119
TI  - NBS1 is a prostate cancer susceptibility gene.
AB  - To evaluate whether an inactivating mutation in the gene for the Nijmegen
      breakage syndrome (NBS1) plays a role in the etiology of prostate cancer, we
      compared the prevalence of the 657del5 NBS1 founder allele in 56 patients with
      familial prostate cancer, 305 patients with nonfamilial prostate cancer, and 1500
      control subjects from Poland. Loss of heterozygosity analysis also was performed
      on DNA samples isolated from 17 microdissected prostate cancers, including 8 from
      carriers of the 657del5 mutation. The NBS1 founder mutation was present in 5 of
      56 (9%) patients with familial prostate cancer (odds ratio, 16; P < 0.0001), 7 of
      305 (2.2%) patients with nonfamilial prostate cancer (odds ratio, 3.9; P = 0.01),
      and 9 of 1500 control subjects (0.6%). The wild-type NBS1 allele was lost in
      seven of eight prostate tumors from carriers of the 657del5 allele, but loss of
      heterozygosity was seen in only one of nine tumors from noncarriers (P = 0.003).
      These findings suggest that heterozygous carriers of the NBS1 founder mutation
      exhibit increased susceptibility to prostate cancer and that the cancers that
      develop in the prostates of carriers are functionally homozygous for the
      mutation.

PMID- 14973120
TI  - Characterization of two methanopterin biosynthesis mutants of Methylobacterium
      extorquens AM1 by use of a tetrahydromethanopterin bioassay.
AB  - An enzymatic assay was developed to measure tetrahydromethanopterin (H(4)MPT)
      levels in wild-type and mutant cells of Methylobacterium extorquens AM1. H(4)MPT
      was detectable in wild-type cells but not in strains with a mutation of either
      the orf4 or the dmrA gene, suggesting a role for these two genes in H(4)MPT
      biosynthesis. The protein encoded by orf4 catalyzed the reaction of
      ribofuranosylaminobenzene 5'-phosphate synthase, the first committed step of
      H(4)MPT biosynthesis. These results provide the first biochemical evidence for
      H(4)MPT biosynthesis genes in bacteria.

PMID- 14973121
TI  - Bordetella species are distinguished by patterns of substantial gene loss and
      host adaptation.
AB  - Pathogens of the bacterial genus Bordetella cause respiratory disease in humans
      and animals. Although virulence and host specificity vary across the genus, the
      genetic determinants of this diversity remain unidentified. To identify genes
      that may underlie key phenotypic differences between these species and clarify
      their evolutionary relationships, we performed a comparative analysis of genome
      content in 42 Bordetella strains by hybridization of genomic DNA to a microarray
      representing the genomes of three Bordetella species and by subtractive
      hybridization. Here we show that B. pertussis and B. parapertussis are
      predominantly differentiated from B. bronchiseptica by large, species-specific
      regions of difference, many of which encode or direct synthesis of surface
      structures, including lipopolysaccharide O antigen, which may be important
      determinants of host specificity. The species also exhibit sequence diversity at
      a number of surface protein-encoding loci, including the fimbrial major subunit
      gene, fim2. Gene loss, rather than gene acquisition, accompanied by the
      proliferation of transposons, has played a fundamental role in the evolution of
      the pathogenic bordetellae and may represent a conserved evolutionary mechanism
      among other groups of microbial pathogens.

PMID- 14973122
TI  - Evidence for a symbiosis island involved in horizontal acquisition of pederin
      biosynthetic capabilities by the bacterial symbiont of Paederus fuscipes beetles.
AB  - Pederin belongs to a group of antitumor compounds found in terrestrial beetles
      and marine sponges. It is used by apparently all members of the rove beetle
      genera Paederus and Paederidus as a chemical defense against predators. However,
      a recent analysis of the putative pederin biosynthesis (ped) gene cluster
      strongly suggests that pederin is produced by bacterial symbionts. We have
      sequenced an extended region of the symbiont genome to gain further insight into
      the biology of this as-yet-unculturable bacterium and the evolution of pederin
      symbiosis. Our data indicate that the symbiont is a very close relative of
      Pseudomonas aeruginosa that has acquired several foreign genetic elements by
      horizontal gene transfer. Besides one functional tellurite resistance operon, the
      region contains a genomic island spanning 71.6 kb that harbors the putative
      pederin biosynthetic genes. Several decayed insertion sequence elements and the
      mosaic-like appearance of the island suggest that the acquisition of the ped
      symbiosis genes was followed by further insertions and rearrangements. A
      horizontal transfer of genes for the biosynthesis of protective substances could
      explain the widespread occurrence of pederin-type compounds in unrelated animals
      from diverse habitats.

PMID- 14973123
TI  - Apurinic/apyrimidinic endonuclease (APE/REF-1) haploinsufficient mice display
      tissue-specific differences in DNA polymerase beta-dependent base excision
      repair.
AB  - Apurinic/apyrimidinic (AP) endonuclease (APE) is a multifunctional protein
      possessing both DNA repair and redox regulatory activities. In base excision
      repair (BER), APE is responsible for processing spontaneous, chemical, or
      monofunctional DNA glycosylase-initiated AP sites via its 5'-endonuclease
      activity and 3'-"end-trimming" activity when processing residues produced as a
      consequence of bifunctional DNA glycosylases. In this study, we have fully
      characterized a mammalian model of APE haploinsufficiency by using a mouse
      containing a heterozygous gene-targeted deletion of the APE gene (Apex(+/-)). Our
      data indicate that Apex(+/-) mice are indeed APE-haploinsufficient, as exhibited
      by a 40-50% reduction (p < 0.05) in APE mRNA, protein, and 5'-endonuclease
      activity in all tissues studied. Based on gene dosage, we expected to see a
      concomitant reduction in BER activity; however, by using an in vitro G:U mismatch
      BER assay, we observed tissue-specific alterations in monofunctional glycosylase
      initiated BER activity, e.g. liver (35% decrease, p < 0.05), testes (55%
      increase, p < 0.05), and brain (no significant difference). The observed changes
      in BER activity correlated tightly with changes in DNA polymerase beta and AP
      site DNA binding levels. We propose a mechanism of BER that may be influenced by
      the redox regulatory activity of APE, and we suggest that reduced APE may render
      a cell/tissue more susceptible to dysregulation of the polymerase beta-dependent
      BER response to cellular stress.

PMID- 14973124
TI  - The three-dimensional structure of invertase (beta-fructosidase) from Thermotoga
      maritima reveals a bimodular arrangement and an evolutionary relationship between
      retaining and inverting glycosidases.
AB  - Thermotoga maritima invertase (beta-fructosidase) hydrolyzes sucrose to release
      fructose and glucose, which are major carbon and energy sources for both
      prokaryotes and eukaryotes. The name "invertase" was given to this enzyme over a
      century ago, because the 1:1 mixture of glucose and fructose that it produces was
      named "invert sugar." Despite its name, the enzyme operates with a mechanism
      leading to the retention of the anomeric configuration at the site of cleavage.
      The enzyme belongs to family GH32 of the sequence-based classification of
      glycosidases. The crystal structure, determined at 2-A resolution, reveals two
      modules, namely a five-bladed beta-propeller with structural similarity to the
      beta-propeller structures of glycosidase from families GH43 and GH68 connected to
      a beta-sandwich module. Three carboxylates at the bottom of a deep, negatively
      charged funnel-shaped depression of the beta-propeller are essential for
      catalysis and function as nucleophile, general acid, and transition state
      stabilizer, respectively. The catalytic machinery of invertase is perfectly
      superimposable to that of the enzymes of families GH43 and GH68. The variation in
      the position of the furanose ring at the site of cleavage explains the different
      mechanisms evident in families GH32 and GH68 (retaining) and GH43 (inverting)
      furanosidases.

PMID- 14973125
TI  - Rapid hepatic metabolism of 7-ketocholesterol by 11beta-hydroxysteroid
      dehydrogenase type 1: species-specific differences between the rat, human, and
      hamster enzyme.
AB  - The role of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in the local
      activation of the glucocorticoid receptor by converting inactive 11
      ketoglucocorticoids to active 11beta-hydroxyglucocorticoids is well established.
      Currently, 11beta-HSD1 is considered a promising target for treatment of obese
      and diabetic patients. Here, we demonstrate a role of 11beta-HSD1 in the
      metabolism of 7-ketocholesterol (7KC), the major dietary oxysterol. Comparison of
      recombinant 11beta-HSD1, transiently expressed in human embryonic kidney 293
      cells, revealed the stereo-specific interconversion of 7KC and 7beta
      hydroxycholesterol by rat and human 11beta-HSD1, whereas the hamster enzyme
      interconverted 7alpha-hydroxycholesterol, 7beta-hydroxycholesterol, and 7KC. In
      contrast to lysates, which efficiently catalyzed both oxidation and reduction,
      intact cells exclusively reduced 7KC. These findings were confirmed using rat and
      hamster liver homogenates, intact rat hepatocytes, and intact hamster liver
      tissue slices. Reduction of 7KC was abolished upon inhibition of 11beta-HSD1 by
      carbenoxolone (CBX) or 2'-hydroxyflavanone. In vivo, after gavage feeding rats,
      7KC rapidly appeared in the liver and was converted to 7beta-hydroxycholesterol.
      CBX significantly decreased the ratio of 7beta-hydroxycholesterol to 7KC,
      supporting the evidence from cell culture experiments for 11beta-HSD1-dependent
      reduction of 7KC to 7beta-hydroxycholesterol. Upon inhibition of 11beta-HSD1 by
      CBX, 7KC tended to accumulate in the liver, and plasma 7KC concentration
      increased. Together, our results suggest that 11beta-HSD1 efficiently catalyzes
      the first step in the rapid hepatic metabolism of dietary 7KC, which may explain
      why dietary 7KC has little or no effect on the development of atherosclerosis.

PMID- 14973126
TI  - The structural basis of the TIM10 chaperone assembly.
AB  - Tim9 and Tim10 are essential components of the "small Tim" family of proteins
      that facilitate insertion of polytopic proteins at the inner mitochondrial
      membrane. The small Tims are themselves imported from the cytosol and are
      organized in specific translocation assemblies in the intermembrane space. Their
      conformational properties and how these influence the mechanism of assembly
      remain poorly understood. Moreover, the three-dimensional structure of the TIM10
      complex is unknown. We have characterized the structural properties of these
      proteins in their free and assembled states using NMR, circular dichroism, and
      small angle x-ray scattering. We show that the free proteins are largely unfolded
      in their reduced assembly-incompetent state and molten globules in their oxidized
      assembly-competent state. Tim10 appears less structured than Tim9 in their
      respective free oxidized forms and undergoes a larger structural change than Tim9
      upon complexation. The NMR data here demonstrates unequivocally that only the
      oxidized states of the Tim9 and Tim10 proteins are capable of forming a complex.
      Zinc binding stabilizes the reduced state against proteolysis without
      significantly affecting the secondary structure. Solution x-ray scattering was
      used to obtain a molecular envelope for the subunits individually and for their
      fully functional TIM10 complex. Ab initio shape reconstructions based on the
      scattering data has allowed us to obtain the first low resolution three
      dimensional structure of the TIM10 complex. This is a novel structure that
      displays extensive surface hydrophobicity. The structure also provides an
      explanation for the escorting function of this non-ATP-powered chaperone
      particle.

PMID- 14973127
TI  - Functional TIM10 chaperone assembly is redox-regulated in vivo.
AB  - The TIM10 chaperone facilitates the insertion of hydrophobic proteins at the
      mitochondrial inner membrane. Here we report the novel molecular mechanism of
      TIM10 assembly. This process crucially depends on oxidative folding in
      mitochondria and involves: (i) import of the subunits in a Cys-reduced and
      unfolded state; (ii) folding to an assembly-competent structure maintained by
      intramolecular disulfide bonding of their four conserved cysteines; and (iii)
      assembly of the oxidized zinc-devoid subunits to the functional complex. We show
      that intramolecular disulfide bonding occurs in vivo, whereas intermolecular
      disulfides observed in vitro are abortive intermediates in the assembly pathway.
      This novel mechanism of compartment-specific redox-regulated assembly is crucial
      for the formation of a functional TIM10 chaperone.

PMID- 14973128
TI  - An endostatin-derived peptide interacts with integrins and regulates actin
      cytoskeleton and migration of endothelial cells.
AB  - Endostatin, the C-terminal fragment of collagen XVIII, is a potent inhibitor of
      angiogenesis and endothelial cell migration. To define its critical cell
      interaction domains we used endostatin-derived synthetic peptides containing
      surface-exposed sequences. We observed that, when immobilized, an arginine-rich
      peptide of 11 amino acids from its N terminus efficiently promoted endothelial
      cell adhesion through beta(1) integrin- and heparin-dependent mechanisms. In
      addition, the peptide induced the formation of membrane ruffles and focal
      contacts. In the soluble form, the peptide inhibited basic fibroblast growth
      factor-induced directional migration and tubular morphogenesis of microvascular
      endothelial cells. Accordingly, the peptide induced the loss of focal adhesions
      and actin stress fibers in these cells. Substitution of the arginine residues
      with alanines resulted in the loss of these properties. In the current study we
      describe a putative integrin-binding sequence with anti-migratory activity within
      endostatin.

PMID- 14973129
TI  - Calcyclin, a Ca2+ ion-binding protein, contributes to the anabolic effects of
      simvastatin on bone.
AB  - In vitro treatment with a pharmacological dose of simvastatin, a potent pro-drug
      of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, stimulates bone
      formation. In our study, simvastatin stimulated differentiation of osteoblasts
      remarkably in a dose-dependent manner, with minimal effect on proliferation. To
      identify the mediators of the anabolic effects of simvastatin on osteoblasts, we
      tried to identify and characterize simvastatin-induced proteins by using
      proteomic analysis. Calcyclin was significantly up-regulated by more than 10
      times, and annexin I was also up-regulated by simvastatin. However, annexin III,
      vimentin, and tropomyosin were down-regulated. Up-regulated calcyclin mRNA by
      simvastatin was validated by reverse transcription in mouse calvarial cells. In
      confocal microscope analysis, green fluorescence protein-calcyclin fusion protein
      was ubiquitously observed in the of MC3T3-E1 cells transfected with green
      fluorescence protein-calcyclin cDNA containing plasmid and was quickly
      concentrated in the nucleus 20 min after simvastatin treatment. Overexpression of
      calcyclin cDNA stimulated both the proliferation and expression of alkaline
      phosphatase mRNA significantly, without exposure to simvastatin in MC3T3-E1
      cells. However, both the rate of proliferation of the osteoblasts and the
      expression of alkaline phosphatase mRNA were suppressed significantly 1 day after
      treatment with the calcyclin-specific small interference RNA, and furthermore,
      simvastatin did not overcome this suppression in the small interference RNA
      pretreated MC3T3-E1 cells. In conclusion, calcyclin is one of the candidate
      proteins that plays a role in osteoblastogenesis in response to simvastatin,
      although the precise functions of calcyclin in osteoblast remain to be verified.

PMID- 14973130
TI  - Phosducin facilitates light-driven transducin translocation in rod
      photoreceptors. Evidence from the phosducin knockout mouse.
AB  - Phosducin is a photoreceptor-specific protein known to interact with the beta
      gamma subunits of G proteins. In pursuit of the function of phosducin, we tested
      the hypothesis that it regulates the light-driven translocation of G protein
      transducin from the outer segments of rod photoreceptors to other compartments of
      the rod cell. Transducin translocation has been previously shown to contribute to
      rod adaptation to bright illumination, yet the molecular mechanisms underlying
      the translocation phenomenon remain unknown. In this study we provide two major
      lines of evidence in support of the role of phosducin in transducin
      translocation. First, we have demonstrated that transducin beta gamma subunits
      interact with phosducin along their entire intracellular translocation route, as
      evident from their co-precipitation in serial tangential sections from light
      adapted but not dark-adapted retinas. Second, we generated a phosducin knockout
      mouse and found that the degree of light-driven transducin translocation in the
      rods of these mice was significantly reduced as compared with that observed in
      the rods of wild type animals. In knockout animals the translocation of
      transducin beta gamma subunits was affected to a larger degree than the
      translocation of the alpha subunit. We also found that the amount of phosducin in
      rods is sufficient to interact with practically all of the transducin present in
      these cells and that the subcellular distribution of phosducin is consistent with
      that of a soluble protein evenly distributed throughout the entire rod cytoplasm.
      Together, these data indicate that phosducin binding to transducin beta gamma
      subunits facilitates transducin translocation. We suggest that the mechanism of
      phosducin action is based on the reduction of transducin affinity to the
      membranes of rod outer segments, achieved by keeping the transducin beta gamma
      subunits apart from the alpha subunit. This increased solubility of transducin
      would make it more susceptible to translocation from the outer segments.

PMID- 14973131
TI  - A new intrinsic thermal parameter for enzymes reveals true temperature optima.
AB  - Two established thermal properties of enzymes are the Arrhenius activation energy
      and thermal stability. Arising from anomalies found in the variation of enzyme
      activity with temperature, a comparison has been made of experimental data for
      the activity and stability properties of five different enzymes with theoretical
      models. The results provide evidence for a new and fundamental third thermal
      parameter of enzymes, T(eq), arising from a subsecond timescale-reversible
      temperature-dependent equilibrium between the active enzyme and an inactive (or
      less active) form. Thus, at temperatures above its optimum, the decrease in
      enzyme activity arising from the temperature-dependent shift in this equilibrium
      is up to two orders of magnitude greater than what occurs through thermal
      denaturation. This parameter has important implications for our understanding of
      the connection between catalytic activity and thermostability and of the effect
      of temperature on enzyme reactions within the cell. Unlike the Arrhenius
      activation energy, which is unaffected by the source ("evolved") temperature of
      the enzyme, and enzyme stability, which is not necessarily related to activity,
      T(eq) is central to the physiological adaptation of an enzyme to its
      environmental temperature and links the molecular, physiological, and
      environmental aspects of the adaptation of life to temperature in a way that has
      not been described previously. We may therefore expect the effect of evolution on
      T(eq) with respect to enzyme temperature/activity effects to be more important
      than on thermal stability. T(eq) is also an important parameter to consider when
      engineering enzymes to modify their thermal properties by both rational design
      and by directed enzyme evolution.

PMID- 14973132
TI  - Cytosolic [Ca2+] transients in dictyostelium discoideum depend on the filling
      state of internal stores and on an active sarco/endoplasmic reticulum calcium
      ATPase (SERCA) Ca2+ pump.
AB  - Stimulation of Dictyostelium discoideum with cAMP evokes a change of the
      cytosolic free Ca(2+) concentration ([Ca(2+)](i)). We analyzed the role of the
      filling state of Ca(2+) stores for the [Ca(2+)] transient. Parameters tested were
      the height of the [Ca(2+)](i) elevation and the percentage of responding amoebae.
      After loading stores with Ca(2+), cAMP induced a [Ca(2+)](i) transient in many
      cells. Without prior loading, cAMP evoked a [Ca(2+)](i) change in a few cells
      only. This indicates that the [Ca(2+)](i) elevation is not mediated exclusively
      by Ca(2+) influx but also by Ca(2+) release from stores. Reducing the Ca(2+)
      content of the stores by EGTA preincubation led to a cAMP-activated [Ca(2+)](i)
      increase even at low extracellular [Ca(2+)]. Moreover, the addition of Ca(2+)
      itself elicited a capacitative [Ca(2+)](i) elevation. This effect was not
      observed when stores were emptied by the standard technique of inhibiting
      internal Ca(2+) pumps with 2,5-di-(t-butyl)-1,4-hydroquinone. Therefore, in
      Dictyostelium, an active internal Ca(2+)-ATPase is absolutely required to allow
      for Ca(2+) entry. No influence of the filling state of stores on Ca(2+) influx
      characteristics was found by the Mn(2+)-quenching technique, which monitors the
      rate of Ca(2+) entry. Both basal and cAMP-activated Mn(2+) influx rates were
      similar in control cells and cells with empty stores. By contrast, determination
      of extracellular free Ca(2+) concentration ([Ca(2+)](e)) changes, which represent
      the sum of Ca(2+) influx and efflux, revealed a higher rate of [Ca(2+)](e)
      decrease in EGTA-treated than in control amoebae. We conclude that emptying of
      Ca(2+) stores does not change the rate of Ca(2+) entry but results in inhibition
      of the plasma membrane Ca(2+)-ATPase. Furthermore, the activities of the Ca(2+)
      transport ATPases of the stores are of crucial importance for the regulation of
      [Ca(2+)](i) changes.

PMID- 14973133
TI  - A distinctive electrocatalytic response from the cytochrome c peroxidase of
      nitrosomonas europaea.
AB  - Here the cytochrome c peroxidase (CcP) from Nitrosomonas europaea is examined
      using the technique of catalytic protein film voltammetry. Submonolayers of the
      bacterial diheme enzyme at a pyrolytic graphite edge electrode give catalytic,
      reductive signals in the presence of the substrate hydrogen peroxide. The
      resulting waveshapes indicate that CcP is bound non-covalently in a highly active
      configuration. The native enzyme has been shown to possess two heme groups of low
      and high potential (L and H, -260 and +450 mV versus hydrogen, respectively), and
      here we find that the catalytic waves of the N. europaea enzyme have a midpoint
      potential of >500 mV and a shape that corresponds to a 1-electron process. The
      signals increase in magnitude with hydrogen peroxide concentration, revealing
      Michaelis-Menten kinetics and K(m) = 55 microm. The midpoint potentials shift
      with substrate concentration, indicating the electrochemically active species
      observed in our data corresponds to a catalytic species. The potentials also
      shift with respect to pH, and the pH dependence is interpreted in terms of a two
      pK(a) model for proton binding. Together the data show that the electrochemistry
      of the N. europaea cytochrome c peroxidase is unlike other peroxidases studied to
      date, including other bacterial enzymes. This is discussed in terms of a
      catalytic model for the N. europaea enzyme and compared with other cytochrome c
      peroxidases.

PMID- 14973134
TI  - The protein import machinery of mitochondria.

PMID- 14973135
TI  - Coordination between motor domains in processive kinesins.

PMID- 14973136
TI  - Plasmin-mediated activation of platelets occurs by cleavage of protease-activated
      receptor 4.
AB  - The activation of plasmin from its circulating precursor plasminogen is the
      mechanism of several clot-busting drugs used to clinically treat patients who
      have suffered a stroke; however, plasmin thus generated has been shown to
      activate platelets directly. There has been speculation as to whether plasmin
      interacts with the protease-activated receptors (PARs) because of its similarity
      in amino acid specificity with the classic platelet activator thrombin. We have
      investigated whether plasmin activates platelets via PAR activation through
      multiple complementary approaches. At concentrations sufficient to induce human
      platelet aggregation, plasmin released very little calcium compared with that
      induced by thrombin, the PAR-1 agonist peptide SFLLRN, or the PAR-4 agonist
      peptide AYPGKF. Stimulation of platelets with plasmin initially failed to
      desensitize additional stimulation with SFLLRN or AYPGKF, but a prolonged
      incubation with plasmin desensitized platelets to further stimulation by
      thrombin. The desensitization of PAR-1 had no effect on plasmin-induced platelet
      aggregation and yielded an aggregation profile that was similar to plasmin in
      response to a low dose of thrombin. However, PAR-4 desensitization completely
      eliminated aggregation in response to plasmin. Inclusion of the PAR-1-specific
      antagonist BMS-200261 inhibited platelet aggregation induced by a low dose of
      thrombin but not by plasmin. Additionally, mouse platelets naturally devoid of
      PAR-1 showed a full aggregation response to plasmin in comparison to thrombin.
      Furthermore, human and mouse platelets treated with a PAR-4 antagonist, as well
      as platelets isolated from PAR-4 homozygous null mice, failed to aggregate in
      response to plasmin. Finally, a protease-resistant recombinant PAR-4 was
      refractory to activation by plasmin. We conclude that plasmin induces platelet
      aggregation primarily through slow cleavage of PAR-4.

PMID- 14973137
TI  - GGA1 interacts with the adaptor protein AP-1 through a WNSF sequence in its hinge
      region.
AB  - The Golgi-associated gamma-adaptin-related ADP-ribosylation factor-binding
      proteins (GGAs) are critical components of the transport machinery that mediates
      the trafficking of the mannose 6-phosphate receptors and associated cargo from
      the trans-Golgi network to the endosomes. The GGAs colocalize in vivo with the
      clathrin adaptor protein AP-1 and bind to AP-1 in vitro, suggesting that the two
      proteins may cooperate in packaging the mannose 6-phosphate receptors into
      clathrin-coated vesicles at the trans-Golgi network. Here, we demonstrate that
      the sequence, (382)WNSF(385), in the hinge region of GGA1 mediates its
      interaction with the AP-1 gamma-ear. The Trp and Phe constitute critical amino
      acids in this interaction. The binding of Rabaptin5 to the AP-1 gamma-ear, which
      occurs through a FXXPhi motif, is inhibited by a peptide encoding the GGA1
      (382)WNSF(385) sequence. Moreover, mutations in the AP-1 gamma-ear that abolish
      its interaction with Rabaptin5 also preclude its association with GGA1. These
      results suggest that the GGA1 WXXF-type and Rabaptin5 FXXPhi-type motifs bind to
      the same or highly overlapping sites in the AP-1 gamma-ear. This binding is
      modulated by residues adjacent to the core motifs.

PMID- 14973138
TI  - Opposing roles for ATF6alpha and ATF6beta in endoplasmic reticulum stress
      response gene induction.
AB  - The endoplasmic reticulum (ER) transmembrane proteins, ATF6alpha and ATF6beta,
      are cleaved in response to ER stress, which can be induced by tunicamycin. The
      resulting N-terminal fragments of both ATF6 isoforms, which have conserved basic
      leucine-zipper and DNA binding domains but divergent transcriptional activation
      domains, translocate to the nucleus where they bind to ER stress-response
      elements (ERSE) in ER stress-response genes (ERSRG), such as GRP78. Although it
      is known that ATF6alpha is a potent activator of ERSRGs, the transcriptional
      potency and functions of ATF6beta remain to be explored. Accordingly, N-terminal
      fragments of each ATF6 isoform (N-ATF6alpha and N-ATF6beta) were overexpressed in
      HeLa cells and the effects on GRP78 induction were assessed. When expressed at
      similar levels, N-ATF6alpha conferred approximately 200-fold greater GRP78
      promoter activation than N-ATF6beta. Because ER stress activates nuclear
      translocation of both ATF6alpha and beta and because both bind to ERSEs, the
      effect of co-expressing them on GRP78 induction was assessed. Surprisingly, N
      ATF6beta inhibited N-ATF6alpha-mediated GRP78 promoter activation in a dominant
      negative manner. Moreover, N-ATF6beta inhibited TN-mediated GRP78 promoter
      activation, which requires endogenous ATF6alpha. ATF6 isoform-specific small
      inhibitory RNAs were used to show that, as expected, endogenous ATF6alpha was
      required for maximal ERSRG induction; however, endogenous ATF6beta moderated
      ERSRG induction. These results indicate that compared with ATF6alpha, ATF6beta is
      a very poor activator of ERSRG induction and it represses ATF6alpha-mediated
      ERSRG induction. Thus, ATF6beta may serve as a transcriptional repressor
      functioning in part to regulate the strength and duration of ATF6alpha-mediated
      ERSRG activation during the ER stress response.

PMID- 14973139
TI  - Reconstitution of F factor DNA replication in vitro with purified proteins.
AB  - Jacob, Brenner, and Cuzin pioneered the development of the F plasmid as a model
      system to study replication control, and these investigations led to the
      development of the "replicon model" (Jacob, F., Brenner, S., and Cuzin, F. (1964)
      Cold Spring Harbor Symp. Quant. Biol. 28, 329-348). To elucidate further the
      mechanism of initiation of replication of this plasmid and its control, we have
      reconstituted its replication in vitro with 21 purified host-encoded proteins and
      the plasmid-encoded initiator RepE. The replication in vitro was specifically
      initiated at the F ori (oriV) and required both the bacterial initiator protein
      DnaA and the plasmid-encoded initiator RepE. The wild type dimeric RepE was
      inactive in catalyzing replication, whereas a monomeric mutant form called
      RepE(*) (R118P) was capable of catalyzing vigorous replication. The replication
      topology was mostly of the Cairns form, and the fork movement was unidirectional
      and mostly from right to left. The replication was dependent on the HU protein,
      and the structurally and functionally related DNA bending protein IHF could not
      efficiently substitute for HU. The priming was dependent on DnaG primase. Many of
      the characteristics of the in vitro replication closely mimicked those of in vivo
      replication. We believe that the in vitro system should be very useful in
      unraveling the mechanism of replication initiation and its control.

PMID- 14973140
TI  - Regulation of alpha1(I) collagen messenger RNA decay by interactions with alphaCP
      at the 3'-untranslated region.
AB  - Liver fibrosis is characterized by an increased deposition of extracellular
      matrix proteins, including collagen type I, by activated hepatic stellate cells
      (HSCs). Previous studies have shown that this increase is mediated primarily by a
      post-transcriptional mechanism. In particular, the RNA-binding protein alphaCP
      binds to the alpha1(I) collagen 3'-untranslated region (UTR) and stabilizes this
      RNA in activated, but not quiescent, HSCs. This study examines the role of
      alphaCP in the decay of transcripts containing the collagen 3'-UTR in extracts
      obtained from NIH fibroblasts and quiescent and activated HSCs. Using an in vitro
      decay system, alphaCP binding activity was competed out with the addition of wild
      type oligonucleotides, but not with mutant oligonucleotides. Competition of
      alphaCP binding activity increased the rate of decay of wild type transcripts
      containing the alphaCP 3'-UTR binding site, but not of transcripts containing a
      mutated binding site. Quiescent HSC extracts contain no alphaCP binding activity
      and have no difference in the rate of decay of transcripts with wild type and
      mutant binding sites for alphaCP. The addition of recombinant alphaCP was
      sufficient to increase the half-life of the wild type transcript, whereas that of
      the mutant transcript was minimally changed. In vitro decay assays performed with
      activated HSC extracts that contain alphaCP binding activity demonstrate a
      markedly reduced decay rate of wild type compared with mutant transcripts. In
      vivo small interfering RNA experiments targeting alphaCP showed a reduction of
      the binding activity of alphaCP and a concomitant reduction in intracellular
      levels of alpha1(I) collagen messenger RNA. In conclusion, this study
      demonstrates the direct role of alphaCP in the stabilization of alpha1(I)
      collagen messenger RNA by blocking RNA degradation in activated HSCs.

PMID- 14973141
TI  - Gab1 contributes to cytoskeletal reorganization and chemotaxis in response to
      platelet-derived growth factor.
AB  - Gab1 is a scaffolding/docking protein that has been suggested to play a role in
      signal transduction downstream of certain plasma membrane receptors, including
      platelet-derived growth factor (PDGF) receptors. We found that PDGF induced a
      rapid Gab1 phosphorylation, which depended on the recruitment of Grb2, indicating
      that Grb2 acts as a bridge between Gab1 and the PDGF beta-receptor. PDGF also
      enhanced the binding of Gab1 to the phosphatase SHP-2, but not to p85. To further
      study the role of Gab1 in PDGF signaling, we transfected porcine aortic
      endothelial cells with a doxycycline-inducible Gab1 construct. Increased Gab1
      expression enhanced the recruitment and activation of SHP-2, as well as the
      phosphorylation of the mitogen-activated protein kinases Erk and p38 by PDGF.
      Gab1 expression also enhanced the formation of lamellipodia and cellular
      protrusions. In Gab1-deficient mouse embryonic fibroblasts, the same phenotype
      was induced by restoring the expression of wild-type Gab1, but not a mutant Gab1
      that was unable to associate with SHP-2. These effects of PDGF on the actin
      cytoskeleton were not altered by the inhibition of p38 or Erk, but could be
      blocked by a dominant-negative form of Rac (Asn(17)). Finally, Gab1-deficient
      fibroblasts showed a decreased chemotactic response toward gradients of PDGF as
      compared with wild-type cells. In conclusion, Gab1 plays a selective role in the
      regulation of the mitogen-activated protein kinases Erk and p38 downstream of the
      PDGF beta-receptor, and contributes to cytoskeletal reorganization and chemotaxis
      in response to PDGF.

PMID- 14973142
TI  - Regulation of purified and reconstituted connexin 43 hemichannels by protein
      kinase C-mediated phosphorylation of Serine 368.
AB  - Indirect evidence suggests that the permeability of connexin 43 (Cx43) gap
      junctional channels (connexons) to small organic molecules (M(r) < 1,000) is
      decreased by protein kinase C (PKC)-mediated phosphorylation of Ser-368. However,
      it is currently unknown whether this effect is produced directly by
      phosphorylation of this residue or whether cytoplasmic regulatory factors are
      required for the decrease in Cx43 gap-junctional channel permeability. Here we
      studied the effects of PKC-mediated phosphorylation on purified recombinant wild
      type Cx43 and a PKC-unresponsive mutant (S368A). Our studies show that (a) PKC
      phosphorylates Ser-368, (b) the phosphorylation by PKC of purified and
      reconstituted connexons abolishes sucrose and Lucifer Yellow permeability, (c)
      the regulation of Cx43 by PKC is the direct result of phosphorylation of Ser-368
      and does not involve intermediary regulatory factors, and (d) phosphorylation of
      Ser-368 produces a conformational change in purified Cx43 as demonstrated by
      changes in intrinsic Trp fluorescence and proteolytic digestion pattern. We
      conclude that phosphorylation of Ser-368 by PKC induces a conformational change
      of Cx43 that results in a decrease in connexon permeability.

PMID- 14973143
TI  - Impairment of HERG K(+) channel function by tumor necrosis factor-alpha: role of
      reactive oxygen species as a mediator.
AB  - Congestive heart failure (CHF) is associated with susceptibility to lethal
      arrhythmias and typically increases levels of tumor necrosis factor-alpha (TNF
      alpha) and its receptor, TNFR1. CHF down-regulates rapid delayed-rectifier K(+)
      current (I(Kr)) and delays cardiac repolarization. We studied the effects of TNF
      alpha on cloned HERG K(+) channel (human ether-a-go-go-related gene) in HEK293
      cells and native I(Kr) in canine cardiomyocytes with whole-cell patch clamp
      techniques. TNF-alpha consistently and reversibly decreased HERG current
      (I(HERG)). Effects of TNF-alpha were concentration-dependent, increased with
      longer incubation period, and occurred at clinically relevant concentrations. TNF
      alpha had similar inhibitory effects on I(Kr) and markedly prolonged action
      potential duration (APD) in canine cardiomyocytes. Immunoblotting analysis
      demonstrated that HERG protein level was slightly higher in canine hearts with
      tachypacing-induced CHF than in healthy hearts, and TNF-alpha slightly increased
      HERG protein level in CHF but not in healthy hearts. In cells pretreated with the
      inhibitory anti-TNFR1 antibody, TNF-alpha lost its ability to suppress I(HERG),
      indicating a requirement of TNFR1 activation for HERG suppression. Vitamin E or
      MnTBAP (Mn(III) tetrakis(4-benzoic acid) porphyrin chloride), a superoxide
      dismutase mimic) prevented, whereas the superoxide anion generating system
      xanthine/xanthine oxidase mimicked, TNF-alpha-induced I(HERG) depression. TNF
      alpha caused robust increases in intracellular reactive oxygen species, and
      vitamin E and MnTBAP abolished the increases, in both HEK293 cells and canine
      ventricular myocytes. We conclude that the TNF-alpha/TNFR1 system impairs
      HERG/I(Kr) function mainly by stimulating reactive oxygen species, particularly
      superoxide anion, but not by altering HERG expression; the effect may contribute
      to APD prolongation by TNF-alpha and may be a novel mechanism for
      electrophysiological abnormalities and sudden death in CHF.

PMID- 14973144
TI  - Signals mediating cleavage of intercellular adhesion molecule-1.
AB  - ICAM-1, a membrane-bound receptor, is released as soluble ICAM-1 in inflammatory
      diseases. To delineate mechanisms regulating ICAM-1 cleavage, studies were
      performed in endothelial cells (EC), human embryonic kidney (HEK)-293 cells
      transfected with wild-type (WT) ICAM-1, and ICAM-1 containing single tyrosine-to
      alanine substitutions (Y474A, Y476A, and Y485A) in the cytoplasmic region.
      Tyrosine residues at 474 and 485 become phosphorylated upon ICAM-1 ligation and
      associate with signaling modules. Cleavage was assessed by using an antibody
      against the cytoplasmic tail of ICAM-1, which recognizes intact ICAM-1 and the 7
      kDa membrane-bound fragment remaining after cleavage. Cleavage in HEK-293 WT
      cells was accelerated by phorbol ester PMA, whereas in EC it was induced by tumor
      necrosis factor-alpha. In both cell types, a 7-kDa ICAM-1 remnant was detected.
      Tyrosine phosphatase inhibitors dephostatin and sodium orthovanadate augmented
      cleavage. PD-98059 (MEK kinase inhibitor), geldanamycin and PP2 (Src kinase
      inhibitors), and wortmannin (phosphatidylinositol 3-kinase inhibitor) dose
      dependently inhibited cleavage in both cell types. SB-203580 (p38 inhibitor) was
      more effective in EC, and D609 (PLC inhibitor) mostly affected cleavage in HEK
      293 cells. Cleavage was drastically decreased in Y474A and Y485A, whereas it was
      marginally reduced in Y476A. Surprisingly, phosphorylation was not detectable on
      the 7-kDa fragment of ICAM-1. These results implicate distinct pathways in the
      cleavage process and suggest a preferred signal transmission route for ICAM-1
      shedding in the two cell systems tested. Tyrosine residues Y474 and Y485 within
      the cytoplasmic sequence of ICAM-1 regulate the cleavage process.

PMID- 14973145
TI  - BDNF rescues myosin heavy chain IIB muscle fibers after neonatal nerve injury.
AB  - Neonatal sciatic nerve injury is known to result in an extensive loss of lumbar
      motor neurons as well as the disappearance of their respective muscle fibers in
      the hindlimb musculature. The loss of motor neurons and muscle fibers can be
      prevented by immediate administration of target-derived neurotrophic factors to
      the site of injury. In the present study, we investigated the role of ciliary
      neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in the
      survival and maturation of a subset of motor neurons innervating the extensor
      digitorum longus (EDL) and tibialis anterior (TA) muscles. We have shown that
      combined administration of CNTF and BDNF prevented the loss of motor units after
      neonatal nerve injury and contributed to the maintenance of muscle mass.
      Importantly, this combined neurotrophin regimen also prevented the disappearance
      of muscle fibers that express myosin heavy chain IIB (MyHC IIB) in both EDL and
      TA muscles 3 mo after neonatal sciatic nerve crush. In parallel studies, we
      observed a higher level of BDNF in EDL muscle during the critical period of
      development when motor neurons are highly susceptible to target removal. Given
      our previous findings that combined administration of CNTF with neurotrophin-3
      (NT-3) or neurotrophin-4/5 (NT-4/5) did not result in the rescue of MyHC IIB
      fibers in EDL, the present results show the importance of muscle-derived BDNF in
      the survival and maturation of a subpopulation of motor neurons and of MyHC IIB
      muscle fibers during neonatal development of the neuromuscular system.

PMID- 14973146
TI  - Reduction and uptake of methylene blue by human erythrocytes.
AB  - A thiazine dye reductase has been described in endothelial cells that reduces
      methylene blue (MB), allowing its uptake into cells. Because a different
      mechanism of MB uptake in human erythrocytes has been proposed, we measured MB
      uptake and reduction in this cell type. Oxidized MB (MB(+)) stimulated reduction
      of extracellular ferricyanide in a time- and concentration-dependent manner,
      reflecting extracellular reduction of the dye. Reduced MB was then taken up by
      the cells and partially oxidized to MB(+). Both forms were retained against a
      concentration gradient, and their redox cycling induced an oxidant stress in the
      cells. Whereas concentrations of MB(+) <5 microM selectively oxidized NAD(P)H,
      higher concentrations also oxidized both glutathione (GSH) and ascorbate,
      especially in the absence of d-glucose. MB(+)-stimulated ferricyanide reduction
      was inhibited by thiol reagents with different mechanisms of action. Phenylarsine
      oxide, which is selective for vicinal dithiols in proteins, inhibited MB(+)
      dependent ferricyanide reduction more strongly than it decreased cell GSH and
      pentose phosphate cycle activity, and it did not affect cellular NADPH. Open
      erythrocyte ghost membranes facilitated saturable NAD(P)H oxidation by MB(+),
      which was abolished by pretreating ghosts with low concentrations of trypsin and
      phenylarsine oxide. These results show that erythrocytes sequentially reduce and
      take up MB(+), that both reduced and oxidized forms of the dye are concentrated
      in cells, and that the thiazine dye reductase activity initially responsible for
      MB(+) reduction may correspond to MB(+)-dependent NAD(P)H reductase activity in
      erythrocyte ghosts.

PMID- 14973147
TI  - Involvement of anion channel(s) in the modulation of the transient outward K(+)
      channel in rat ventricular myocytes.
AB  - The cardiac Ca(2+)-independent transient outward K(+) current (I(to)), a major
      repolarizing ionic current, is markedly affected by Cl(-) substitution and anion
      channel blockers. We reexplored the mechanism of the action of anions on I(to) by
      using whole cell patch-clamp in single isolated rat cardiac ventricular myocytes.
      The transient outward current was sensitive to blockade by 4-aminopyridine (4-AP)
      and was abolished by Cs(+) substitution for intracellular K(+). Replacement of
      most of the extracellular Cl(-) with less permeant anions, aspartate (Asp(-)) and
      glutamate (Glu(-)), markedly suppressed the current. Removal of external Na(+) or
      stabilization of F-actin with phalloidin did not significantly affect the
      inhibitory action of less permeant anions on I(to). In contrast, the permeant Cl(
      ) substitute Br(-) did not markedly affect the current, whereas F(-) substitution
      for Cl(-) induced a slight inhibition. The I(to) elicited during Br(-)
      substitution for Cl(-) was also sensitive to blockade by 4-AP. The ability of Cl(
      ) substitutes to induce rightward shifts of the steady-state inactivation curve
      of I(to) was in the following sequence: NO(3)(-) > Cl(-) approximately Br(-) >
      gluconate(-) > Glu(-) > Asp(-). Depolymerization of actin filaments with
      cytochalasin D (CytD) induced an effect on the steady-state inactivation of I(to)
      similar to that of less permeant anions. Fluorescent phalloidin staining
      experiments revealed that CytD-pretreatment significantly decreased the intensity
      of FITC-phalloidin staining of F-actin, whereas Asp(-) substitution for Cl(-) was
      without significant effect on the intensity. These results suggest that the I(to)
      channel is modulated by anion channel(s), in which the actin cytoskeleton may be
      implicated.

PMID- 14973148
TI  - OKP cells express the Na-dicarboxylate cotransporter NaDC-1.
AB  - Urinary citrate concentration, a major factor in the formation of kidney stones,
      is primarily determined by its rate of reabsorption in the proximal tubule.
      Citrate reabsorption is mediated by the Na-dicarboxylate cotransporter-1 (NaDC
      1). The opossum kidney (OKP) cell line possesses many characteristics of the
      renal proximal tubule. The OKP NaDC-1 (oNaDC-1) cDNA was cloned and encodes a 2.4
      kb mRNA. When injected into Xenopus oocytes, the cotransporter is expressed and
      demonstrates Na-coupled citrate transport with a stoichiometry of >or=3 Na:1
      citrate, specificity for di- and tricarboxylates, pH-dependent citrate transport,
      and pH-independent succinate transport, all characteristics of the other NaDC-1
      orthologs. Chronic metabolic acidosis increases proximal tubule citrate
      reabsorption, leading to profound hypocitraturia and an increased risk for stone
      formation. Under the conditions studied, endogenous OKP NaDC-1 mRNA abundance is
      not regulated by changes in media pH. In OKP cells transfected with a green
      fluorescent protein-oNaDC-1 construct, however, media acidification increases Na
      dependent citrate uptake, demonstrating posttranscriptional acid regulation of
      NaDC-1 activity.

PMID- 14973149
TI  - Transition states of the high-affinity rabbit Na(+)/glucose cotransporter SGLT1
      as determined from measurement and analysis of voltage-dependent charge
      movements.
AB  - The charge-membrane voltage (Q-V) distribution of wild-type rabbit Na(+)/glucose
      transporter (rSGLT1) expressed in Xenopus oocytes was investigated in the absence
      of glucose, using the two-electrode voltage-clamp technique. Although this
      distribution is generally believed to be well represented by a two-state
      Boltzmann equation, we recently provided evidence for the existence of at least
      four states (Krofchick D and Silverman M. Biophys J 84: 3690-3702, 2003),
      confirming an earlier finding for human SGLT1 (Chen XZ, Coady MJ, and Lapointe
      JY. Biophys J 71: 2544-2552, 1996). We now extend our study of rSGLT1 pre-steady
      state currents, employing high-resolution measurement and analysis of the Q-V
      distribution. A ramp, instead of a step, voltage change was used to prevent
      saturation of the apparatus in the first approximately 1 ms. Transient currents
      were integrated out to 150 ms, instead of the standard 50-100 ms. Measurements
      were taken every 10 mV instead of the standard 20 mV. The Q-V distribution was
      fit with a two-, three-, and four-state Boltzmann equation and was described best
      by the three-state equation. The three-state fit produced two valences of 0.45
      and 1.1 at two V(0.5) values of -48 and -7.7, respectively. Our findings are
      critically compared with other published studies and the differences are
      discussed. An implication of the three-state fit is that the turnover rate of
      rSGLT1 is 34 s(-1), i.e., 54% greater than previously reported (22 s(-1)). Our
      new findings support the concept that the sugar-free model of SGLT1 is more
      complex than generally accepted, most likely involving a minimum of four
      transition states.

PMID- 14973150
TI  - Molecular and clinical epidemiology of vancomycin-resistant Enterococcus
      faecalis.
AB  - OBJECTIVES: With the recent emergence of vancomycin-resistant (VR) Staphylococcus
      aureus, subsequent to the suggested transfer of the vanA resistance gene from
      Enterococcus faecalis, we sought to determine risk factors for acquisition of VR
      E. faecalis and to evaluate the molecular epidemiology of this less-prevalent and
      less-studied species of VR enterococcus. METHODS: We compared clinical isolates
      of VR E. faecalis from 71 patients, collected over 12 years in a large community
      teaching hospital, with isolates from 126 patients with vancomycin-susceptible E.
      faecalis. RESULTS: Risk factors for VR E. faecalis acquisition by multivariate
      analysis were nursing home residence (P = 0.0005), haemodialysis (P = 0.009),
      decubitus ulcers (P = 0.03) and receipt of parenteral vancomycin (P = 0.0002).
      Twenty-one percent of VR E. faecalis demonstrated vanA and 79% vanB resistance.
      The number of VanA isolates increased over time. Molecular analysis showed vanA
      or vanB in multiple PFGE groups. CONCLUSIONS: The results of this study suggest
      gene dissemination among some isolates and intra-hospital spread of other
      isolates. The risk factors identified clearly suggest that VR E. faecalis is a
      nosocomial pathogen and should be considered in infection control practices.
      Further surveillance of VR E. faecalis is warranted, due to the potential spread
      of vancomycin resistance among enterococci and staphylococci.

PMID- 14973151
TI  - Disc diffusion susceptibility testing of Haemophilus influenzae by NCCLS
      methodology using low-strength ampicillin and co-amoxiclav discs.
AB  - OBJECTIVES: The objective of this multicentre study was to define the accuracy
      and reproducibility of the NCCLS disc diffusion method for Haemophilus influenzae
      against ampicillin and co-amoxiclav in Finnish clinical microbiology
      laboratories. Special attention was paid to the ability of the laboratories to
      detect beta-lactamase-negative ampicillin-resistant (BLNAR) strains. METHODS:
      Three BLNAR and two beta-lactamase-negative ampicillin-susceptible isolates
      (BLNAS)-originating from the American Type Culture Collection (ATCC) and UK
      National External Quality Assessment (UKNEQAS) schemes-were included in this
      study. Susceptibility tests for these isolates were performed in 26 clinical
      microbiology laboratories, in accordance with NCCLS guidelines. Additionally, low
      strength discs for ampicillin (2 microg) and co-amoxiclav (3 microg) were tested.
      RESULTS: The low-strength discs for ampicillin and co-amoxiclav categorized more
      accurately BLNAR and BLNAS H. influenzae isolates than did the high-strength
      discs recommended by the NCCLS. In addition, the high-strength discs produced
      more major errors than the low-strength discs (22 versus six for ampicillin and
      40 versus seven for co-amoxiclav). Great variation occurred in the method
      regardless of the antibiotic concentration of the discs. CONCLUSIONS: The use of
      low-content ampicillin and co-amoxiclav discs is recommended for the
      susceptibility testing of H. influenzae. Interpretative criteria of S > or = 17
      mm and R < or = 13 mm for both discs are suggested.

PMID- 14973152
TI  - In vitro antibacterial activity of the peptide deformylase inhibitor BB-83698.
AB  - OBJECTIVES: BB-83698 is a peptide deformylase inhibitor currently in clinical
      trials in Europe. The purpose of this study was to provide additional
      susceptibility data from clinical isolates, including drug-resistant strains.
      METHODS: The in vitro activities of BB-83698 and comparators were determined
      against 281 streptococci, 154 Staphylococcus aureus, 110 Haemophilus influenzae
      and 50 Moraxella catarrhalis strains selected for their resistance phenotypes.
      Broth microdilution MICs and MBCs were determined according to NCCLS guidelines.
      RESULTS: The MIC90s were 0.25-0.5 mg/L for S. pneumoniae, including penicillin-,
      erythromycin-, levofloxacin- and multidrug-resistant strains. The MIC90s for
      Streptococcus pyogenes and Streptococcus agalactiae were 0.12 mg/L and for
      viridans streptococci, the MIC90 was 0.5 mg/L. Against S. aureus, including
      oxacillin- and levofloxacin-resistant strains, and vancomycin-intermediate
      strains, the MIC90 was 8 mg/L. Against beta-lactamase-negative and -positive H.
      influenzae, the MIC90s were 32 and 64 mg/L, respectively, and against both beta
      lactamase-negative and -positive M. catarrhalis the MIC90 was 0.12 mg/L. In MBC
      studies, the ratio of MBC/MIC was 1:1 or 2:1 against 31% of S. pneumoniae, 33% of
      S. aureus, 63% of H. influenzae and 9% of M. catarrhalis. CONCLUSIONS: Although
      BB-83698 has reduced in vitro activity against H. influenzae, it is a potent
      antimicrobial with excellent activity against streptococci and Moraxella.

PMID- 14973153
TI  - In vitro susceptibility of Stenotrophomonas maltophilia isolates: comparison of
      disc diffusion, Etest and agar dilution methods.
AB  - The disc diffusion, Etest and agar dilution techniques were compared to evaluate
      the antimicrobial susceptibility profile of 70 Stenotrophomonas maltophilia
      isolates to seven antimicrobial agents. The S. maltophilia isolates were
      consecutively collected from May 2000 to May 2002 from individual patients, who
      were hospitalized in a private Brazilian hospital. The antimicrobial
      susceptibility tests were carried out and interpreted according to the National
      Committee for Clinical Laboratory Standards (NCCLS) recommendations. The Etest
      was carried out according to the manufacturer's instructions. There was good
      agreement among the distinct susceptibility testing results for chloramphenicol,
      doxycycline, gatifloxacin, trimethoprim-sulfamethoxazole and ticarcillin
      clavulanate, suggesting that the disc diffusion and Etest methods are reliable
      for testing this group of antimicrobials against S. maltophilia. In contrast, a
      weak correlation was found between the disc diffusion and agar dilution
      techniques for testing polymyxin B and colistin with unacceptable very major
      error rates (18.1% and 22.7% for polymyxin B and colistin, respectively).
      Trimethoprim- sulfamethoxazole (MIC50, 0.06 mg/L; 98.5% susceptible) and
      gatifloxacin (MIC50, 0.12 mg/L; 98.5% susceptible) were the most potent
      antimicrobial agents tested against S. maltophilia isolates. In contrast, the
      worst in vitro activity was found for ticarcillin-clavulanate (MIC50, 16 mg/L;
      59.1% susceptible). Although our results confirm that trimethoprim
      sulfamethoxazole, gatifloxacin and doxycycline have an excellent in vitro
      activity against S. maltophilia, further clinical studies are necessary to
      evaluate the clinical efficacy of these compounds for the treatment of S.
      maltophilia infections, since no randomized controlled trials have been carried
      out and no correlation between the clinical response and susceptibility testing
      results has been reported.

PMID- 14973154
TI  - Short-course treatment regimen to identify potential antituberculous agents in a
      murine model of tuberculosis.
AB  - OBJECTIVE: Designing a more rapid method to test antimycobacterial agents in a
      murine model would significantly improve the drug development process. We
      describe a short-course in vivo treatment model that could be used to screen
      potential antituberculous drugs. METHODS: In this model, C57BL/6 mice were
      infected intranasally with approximately 10(6) viable Mycobacterium tuberculosis
      organisms. Treatment began 1 day post-infection and was administered for 2 days.
      Mice were euthanized 3 days post-infection and their right lungs were removed and
      cell counts determined. Several antimycobacterial agents with superior in vivo
      activity in a 4 week treatment model were tested to evaluate the short-course
      treatment model. RESULTS: Two days of isoniazid (25 mg/kg), rifampicin (20
      mg/kg), PNU-100480 (100 mg/kg), gatifloxacin (100 mg/kg), levofloxacin (100
      mg/kg) and sparfloxacin (100 mg/kg) were all able to significantly reduce the
      mycobacterial load in the lungs compared with the untreated control mice.
      CONCLUSIONS: Use of this model to screen potential chemotherapeutic agents will
      save time and resources.

PMID- 14973155
TI  - Use of MGIT 960 for rapid quantitative measurement of the susceptibility of
      Mycobacterium tuberculosis complex to ciprofloxacin and ethionamide.
AB  - OBJECTIVES: Tentative standards for testing MICs for Mycobacterium tuberculosis
      include agar dilution and the BACTEC method. However, the conventional agar
      dilution method requires 3-5 weeks to complete; whereas BACTEC, although a rapid
      test, involves the use of radioisotopes. In contrast, the MGIT 960 system uses a
      fluorescence quenching based oxygen sensor that can be read automatically. This
      system is not only robust, safe and simple, but has been validated for
      susceptibility tests of first-line antituberculous agents. METHODS: We evaluated
      46 clinical strains of M. tuberculosis isolated from patients admitted to
      Kaohsiung Veterans General Hospital. Testing of MICs of ciprofloxacin and
      ethionamide was carried out by MGIT 960 and compared with the agar dilution
      method. RESULTS: Good agreement was found between MGIT 960 and agar dilution. The
      greatest concordance between the agar dilution and MGIT assay at +/-1 and +/-2
      dilution was 80.4% and 97.8% for ciprofloxacin, and 82.6% and 93.5% for
      ethionamide, respectively. CONCLUSION: MGIT 960 was found to be comparable to the
      current NCCLS standard method, agar dilution, and has the advantage of being
      rapid (obtaining results within 5-17 days, average 8.9 days) and easy to achieve
      standardization.

PMID- 14973156
TI  - Spectrum of antibiotic resistance of the Spain14-5 Streptococcus pneumoniae clone
      over a 22 year period.
AB  - OBJECTIVE: To study the characteristics and the evolution through time of a
      single Streptococcus pneumoniae multidrug-resistant international clone. METHODS:
      From 1981 to 2002, the presence of the multidrug-resistant Spain14-5 clone was
      studied among the 4201 S. pneumoniae isolated in Gipuzkoa (northern Spain).
      RESULTS: Overall, 93 isolates belonging to the Spain14-5 clone were identified.
      The first isolate of this clone was detected in 1981 and was already resistant to
      beta-lactams, erythromycin, clindamycin and chloramphenicol. The reference strain
      from the international collection for this clone was susceptible to macrolides
      and lincosamides whereas most of the isolates studied, including the first
      isolate detected in 1981, were resistant to macrolides and had the erm(B) gene
      encoding macrolide resistance. CONCLUSIONS: The clone was genetically stable
      through time, was multiresistant since its inception and has recently become
      highly resistant to fluoroquinolones. The characteristic antibiotic resistance
      pattern of this clone should include erythromycin resistance.

PMID- 14973157
TI  - Differential proteomics reveals multiple components in retrogradely transported
      axoplasm after nerve injury.
AB  - Information on axonal damage is conveyed to neuronal cell bodies by a number of
      signaling modalities, including the post-translational modification of axoplasmic
      proteins. Retrograde transport of a subset of such proteins is thought to induce
      or enhance a regenerative response in the cell body. Here we report the use of a
      differential 2D-PAGE approach to identify injury-correlated retrogradely
      transported proteins in nerves of the mollusk Lymnaea. A comprehensive series of
      gels at different pI ranges allowed resolution of approximately 4000 spots by
      silver staining, and 172 of these were found to differ between lesioned versus
      control nerves. Mass spectrometric sequencing of 134 differential spots allowed
      their assignment to over 40 different proteins, some belonging to a vesicular
      ensemble blocked by the lesion and others comprising an up-regulated ensemble
      highly enriched in calpain cleavage products of an intermediate filament termed
      RGP51 (retrograde protein of 51 kDa). Inhibition of RGP51 expression by RNA
      interference inhibits regenerative outgrowth of adult Lymnaea neurons in culture.
      These results implicate regulated proteolysis in the formation of retrograde
      injury signaling complexes after nerve lesion and suggest that this signaling
      modality utilizes a wide range of protein components.

PMID- 14973158
TI  - The Melampsora lini AvrL567 avirulence genes are expressed in haustoria and their
      products are recognized inside plant cells.
AB  - The Linum usitatissimum (flax) L gene alleles, which encode nucleotide binding
      site-Leu rich repeat class intracellular receptor proteins, confer resistance
      against the Melampsora lini (flax rust) fungus. At least 11 different L
      resistance specificities are known, and the corresponding avirulence genes in M.
      lini map to eight independent loci, some of which are complex and encode multiple
      specificities. We identified an M. lini cDNA marker that cosegregates in an F2
      rust family with a complex locus determining avirulence on the L5, L6, and L7
      resistance genes. Two related avirulence gene candidates, designated AvrL567-A
      and AvrL567-B, were identified in a genomic DNA contig from the avirulence
      allele, whereas the corresponding virulence allele contained a single copy of a
      related gene, AvrL567-C. Agrobacterium tumefaciens-mediated transient expression
      of the mature AvrL567-A or AvrL567-B (but not AvrL567-C) proteins as
      intracellular products in L. usitatissimum and Nicotiana tabacum (tobacco)
      induced a hypersensitive response-like necrosis that was dependent on
      coexpression of the L5, L6, or L7 resistance gene. An F1 seedling lethal or
      stunted growth phenotype also was observed when transgenic L. usitatissimum
      plants expressing AvrL567-A or AvrL567-B (but not AvrL567-C) were crossed to
      resistant lines containing L5, L6, or L7. The AvrL567 genes are expressed in rust
      haustoria and encode 127 amino acid secreted proteins. Intracellular recognition
      of these rust avirulence proteins implies that they are delivered into host cells
      across the plant membrane. Differences in the three AvrL567 protein sequences
      result from diversifying selection, which is consistent with a coevolutionary
      arms race.

PMID- 14973159
TI  - Identification of multivesicular bodies as prevacuolar compartments in Nicotiana
      tabacum BY-2 cells.
AB  - Little is known about the dynamics and molecular components of plant prevacuolar
      compartments (PVCs). We have demonstrated recently that vacuolar sorting receptor
      (VSR) proteins are concentrated on PVCs. In this study, we generated transgenic
      Nicotiana tabacum (tobacco) BY-2 cell lines expressing two yellow fluorescent
      protein (YFP)-fusion reporters that mark PVC and Golgi organelles. Both
      transgenic cell lines exhibited typical punctate YFP signals corresponding to
      distinct PVC and Golgi organelles because the PVC reporter colocalized with VSR
      proteins, whereas the Golgi marker colocalized with mannosidase I in confocal
      immunofluorescence. Brefeldin A induced the YFP-labeled Golgi stacks but not the
      YFP-marked PVCs to form typical enlarged structures. By contrast, wortmannin
      caused YFP-labeled PVCs but not YFP-labeled Golgi stacks to vacuolate. VSR
      antibodies labeled multivesicular bodies (MVBs) on thin sections prepared from
      high-pressure frozen/freeze substituted samples, and the enlarged PVCs also were
      indentified as MVBs. MVBs were further purified from BY-2 cells and found to
      contain VSR proteins via immunogold negative staining. Similar to YFP-labeled
      Golgi stacks, YFP-labeled PVCs are mobile organelles in BY-2 cells. Thus, we have
      unequivocally identified MVBs as PVCs in N. tabacum BY-2 cells. Uptake studies
      with the styryl dye FM4-64 strongly indicate that PVCs also lie on the endocytic
      pathway of BY-2 cells.

PMID- 14973160
TI  - Growth regulators and the control of nucleotide sugar flux.
AB  - A small number of plant growth regulators are involved in the control of cell
      expansion. Despite knowledge of some of their signal transduction cascades,
      surprisingly little is known of how basic cell expansion-related processes, such
      as cell wall biosynthesis, are affected during growth. The Arabidopsis
      (Arabidopsis thaliana) mutant root hair defective1 (rhd1) lacks a functional UDP
      glucose 4-epimerase gene, UGE4, which is involved in channeling UDP-D-galactose
      (UDP-D-Gal) into cell wall polymers. Here, we use rhd1 as a genetic model to
      analyze the physiological and genetic controls of nucleotide sugar flux. We find
      that ethylene specifically suppresses all visible aspects of the rhd1 phenotype.
      The ethylene-triggered suppression of rhd1 is negatively regulated by
      CONSTITUTIVE TRIPLE RESPONSE1 and requires the function of the wild-type genes
      ETHYLENE INSENSITIVE2 (EIN2), EIN4, AUXIN-RESISTENT1, and ETHYLENE-INSENSITIVE
      ROOT1 but does not depend on the activity of wild-type ETHYLENE RECEPTOR1 or EIN3
      genes, highlighting the nonlinearity of ethylene signal transduction. Ethylene
      does not induce the expression of alternative UGE genes but, instead, suppresses
      the expression of two isoforms, UGE1 and UGE3, in a tissue-specific manner.
      Ethylene restores the biosynthesis of galactose-containing xyloglucan and
      arabinosylated galactan cell wall polymers in rhd1 back to wild-type levels.
      However, the dependence on UGE4 of pectic (1-->4)-beta-D-galactan and
      glucuronosyl-modified AGP biosynthesis is exacerbated. Our data suggest that
      ethylene and auxin together participate in the flux control of UDP-D-Gal into
      cell wall polymers and that the genetic control of this process is qualitatively
      distinct from previously described responses to ethylene.

PMID- 14973161
TI  - Plant respiratory burst oxidase homologs impinge on wound responsiveness and
      development in Lycopersicon esculentum.
AB  - Plant respiratory burst oxidase homologs (Rboh) are homologs of the human
      neutrophil pathogen-related gp91(phox). Antisense technology was employed to
      ascertain the biological function of Lycopersicon esculentum (tomato) Rboh. Lines
      with diminished Rboh activity showed a reduced level of reactive oxygen species
      (ROS) in the leaf, implying a role for Rboh in establishing the cellular redox
      milieu. Surprisingly, the antisense plants acquired a highly branched phenotype,
      switched from indeterminate to determinate growth habit, and had fasciated
      reproductive organs. Wound-induced systemic expression of proteinase inhibitor II
      was compromised in the antisense lines, indicating that ROS intermediates
      supplied by Rboh are required for this wound response. Extending these
      observations by transcriptome analysis revealed ectopic leaf expression of
      homeotic MADS box genes that are normally expressed only in reproductive organs.
      In addition, both Rboh-dependent and -independent wound-induced gene induction
      was detected as well as transcript changes related to redox maintenance. The
      results provide novel insights into how the steady state cellular level of ROS is
      controlled and portrays the role of Rboh as a signal transducer of stress and
      developmental responses.

PMID- 14973162
TI  - A new Arabidopsis gene, FLK, encodes an RNA binding protein with K homology
      motifs and regulates flowering time via FLOWERING LOCUS C.
AB  - Posttranscriptional RNA metabolism plays versatile roles in the regulation of
      gene expression during eukaryotic growth and development. It is mediated by a
      group of RNA binding proteins with distinct conserved motifs. In this study, an
      Arabidopsis (Arabidopsis thaliana) gene, designated FLK, was identified and shown
      to encode a putative RNA binding protein with K homology motifs. A mutant in
      which FLK was inactivated by T-DNA insertion exhibited a severe late flowering
      phenotype both in long and short days. The late flowering phenotype was reversed
      by gibberellin and vernalization treatments. The FLOWERING LOCUS C (FLC)
      transcription was greatly upregulated, whereas those of FLOWERING LOCUS T and
      SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 decreased in the mutant. These
      observations demonstrate that FLK regulates the autonomous flowering pathway via
      FLC. It is now evident that a battery of different RNA binding proteins are
      involved in the posttranscriptional regulation of flowering time in Arabidopsis.

PMID- 14973163
TI  - The duplicated B-class heterodimer model: whorl-specific effects and complex
      genetic interactions in Petunia hybrida flower development.
AB  - In both Antirrhinum (Antirrhinum majus) and Arabidopsis (Arabidopsis thaliana),
      the floral B-function, which specifies petal and stamen development, is embedded
      in a heterodimer consisting of one DEFICIENS (DEF)/APETALA3 (AP3)-like and one
      GLOBOSA (GLO)/PISTILLATA (PI)-like MADS box protein. Here, we demonstrate that
      gene duplications in both the DEF/AP3 and GLO/PI lineages in Petunia hybrida
      (petunia) have led to a functional diversification of their respective members,
      which is reflected by partner specificity and whorl-specific functions among
      these proteins. Previously, it has been shown that mutations in PhDEF (formerly
      known as GREEN PETALS) only affect petal development. We have isolated insertion
      alleles for PhGLO1 (FLORAL BINDING PROTEIN1) and PhGLO2 (PETUNIA MADS BOX GENE2)
      and demonstrate unique and redundant properties of PhDEF, PhGLO1, and PhGLO2.
      Besides a full homeotic conversion of petals to sepals and of stamens to carpels
      as observed in phglo1 phglo2 and phdef phglo2 flowers, we found that gene dosage
      effects for several mutant combinations cause qualitative and quantitative
      changes in whorl 2 and 3 meristem fate, and we show that the PHDEF/PHGLO1
      heterodimer controls the fusion of the stamen filaments with the petal tube.
      Nevertheless, when the activity of PhDEF, PhGLO1, and PhGLO2 are considered
      jointly, they basically appear to function as DEF/GLO does in Antirrhinum and to
      a lesser extent as AP3/PI in Arabidopsis. By contrast, our data suggest that the
      function of the fourth B-class MADS box member, the paleoAP3-type PETUNIA HYBRIDA
      TM6 (PhTM6) gene, differs significantly from the known euAP3-type DEF/AP3-like
      proteins; PhTM6 is mainly expressed in the developing stamens and ovary of wild
      type flowers, whereas its expression level is upregulated in whorls 1 and 2 of an
      A-function floral mutant; PhTM6 is most likely not involved in petal development.
      The latter is consistent with the hypothesis that the evolutionary origin of the
      higher eudicot petal structure coincided with the appearance of the euAP3-type
      MADS box genes.

PMID- 14973164
TI  - Microarray expression analyses of Arabidopsis guard cells and isolation of a
      recessive abscisic acid hypersensitive protein phosphatase 2C mutant.
AB  - Oligomer-based DNA Affymetrix GeneChips representing about one-third of
      Arabidopsis (Arabidopsis thaliana) genes were used to profile global gene
      expression in a single cell type, guard cells, identifying 1309 guard cell
      expressed genes. Highly pure preparations of guard cells and mesophyll cells were
      isolated in the presence of transcription inhibitors that prevented induction of
      stress-inducible genes during cell isolation procedures. Guard cell expression
      profiles were compared with those of mesophyll cells, resulting in identification
      of 64 transcripts expressed preferentially in guard cells. Many large gene
      families and gene duplications are known to exist in the Arabidopsis genome,
      giving rise to redundancies that greatly hamper conventional genetic and
      functional genomic analyses. The presented genomic scale analysis identifies
      redundant expression of specific isoforms belonging to large gene families at the
      single cell level, which provides a powerful tool for functional genomic
      characterization of the many signaling pathways that function in guard cells.
      Reverse transcription-PCR of 29 genes confirmed the reliability of GeneChip
      results. Statistical analyses of promoter regions of abscisic acid (ABA)
      regulated genes reveal an overrepresented ABA responsive motif, which is the
      known ABA response element. Interestingly, expression profiling reveals ABA
      modulation of many known guard cell ABA signaling components at the transcript
      level. We further identified a highly ABA-induced protein phosphatase 2C
      transcript, AtP2C-HA, in guard cells. A T-DNA disruption mutation in AtP2C-HA
      confers ABA-hypersensitive regulation of stomatal closing and seed germination.
      The presented data provide a basis for cell type-specific genomic scale analyses
      of gene function.

PMID- 14973165
TI  - Disparate roles for the regulatory A subunit isoforms in Arabidopsis protein
      phosphatase 2A.
AB  - The heterotrimeric protein phosphatase 2A (PP2A) complex comprises a catalytic
      subunit and regulatory A and B subunits that modulate enzyme activity and mediate
      interactions with other proteins. We report here the results of a systematic
      analysis of the Arabidopsis (Arabidopsis thaliana) regulatory A subunit gene
      family, which includes the ROOTS CURL IN NAPHTHYLPHTHALAMIC ACID1 (RCN1), PP2AA2,
      and PP2AA3 genes. All three A subunit isoforms accumulate in the organs of
      seedlings and adult plants, suggesting extensive overlap in expression domains.
      We have isolated pp2aa2 and pp2aa3 mutants and found that their phenotypes are
      largely normal and do not resemble that of rcn1. Whereas rcn1 pp2aa2 and rcn1
      pp2aa3 double mutants exhibit striking abnormalities in all stages of
      development, the pp2aa2 pp2aa3 double mutant shows only modest defects. Together,
      these data suggest that RCN1 performs a cardinal role in regulation of
      phosphatase activity and that PP2AA2 and PP2AA3 functions are unmasked only when
      RCN1 is absent.

PMID- 14973166
TI  - Type-A Arabidopsis response regulators are partially redundant negative
      regulators of cytokinin signaling.
AB  - Type-A Arabidopsis (Arabidopsis thaliana) response regulators (ARRs) are a family
      of 10 genes that are rapidly induced by cytokinin and are highly similar to
      bacterial two-component response regulators. We have isolated T-DNA insertions in
      six of the type-A ARRs and constructed multiple insertional mutants, including
      the arr3,4,5,6,8,9 hextuple mutant. Single arr mutants were indistinguishable
      from the wild type in various cytokinin assays; double and higher order arr
      mutants showed progressively increasing sensitivity to cytokinin, indicating
      functional overlap among type-A ARRs and that these genes act as negative
      regulators of cytokinin responses. The induction of cytokinin primary response
      genes was amplified in arr mutants, indicating that the primary response to
      cytokinin is affected. Spatial patterns of ARR gene expression were consistent
      with partially redundant function of these genes in cytokinin signaling. The arr
      mutants show altered red light sensitivity, suggesting a general involvement of
      type-A ARRs in light signal transduction. Further, morphological phenotypes of
      some arr mutants suggest complex regulatory interactions and gene-specific
      functions among family members.

PMID- 14973167
TI  - Maize centromeres: organization and functional adaptation in the genetic
      background of oat.
AB  - Centromeric DNA sequences in multicellular eukaryotes are often highly repetitive
      and are not unique to a specific centromere or to centromeres at all. Thus, it is
      a major challenge to study the fine structure of individual plant centromeres. We
      used a DNA fiber-fluorescence in situ hybridization approach to study individual
      maize (Zea mays) centromeres using oat (Avena sativa)-maize chromosome addition
      lines. The maize centromere-specific satellite repeat CentC in the addition lines
      allowed us to delineate the size and organization of centromeric DNA of
      individual maize chromosomes. We demonstrate that the cores of maize centromeres
      contain mainly CentC arrays and clusters of a centromere-specific
      retrotransposon, CRM. CentC and CRM sequences are highly intermingled. The amount
      of CentC/CRM sequence varies from approximately 300 to >2800 kb among different
      centromeres. The association of CentC and CRM with centromeric histone H3 (CENH3)
      was visualized by a sequential detection procedure on stretched centromeres. The
      analysis revealed that CENH3 is always associated with CentC and CRM but that not
      all CentC or CRM sequences are associated with CENH3. We further demonstrate that
      in the chromosomal addition lines in which two CenH3 genes were present, one from
      oat and one from maize, the oat CENH3 was consistently incorporated by the maize
      centromeres.

PMID- 14973168
TI  - The F-box protein AhSLF-S2 physically interacts with S-RNases that may be
      inhibited by the ubiquitin/26S proteasome pathway of protein degradation during
      compatible pollination in Antirrhinum.
AB  - Self-incompatibility S-locus-encoded F-box (SLF) proteins have been identified in
      Antirrhinum and several Prunus species. Although they appear to play an important
      role in self-incompatible reaction, functional evidence is lacking. Here, we
      provide several lines of evidence directly implicating a role of AhSLF-S(2) in
      self-incompatibility in Antirrhinum. First, a nonallelic physical interaction
      between AhSLF-S(2) and S-RNases was demonstrated by both coimmunoprecipitation
      and yeast two-hybrid assays. Second, AhSLF-S(2) interacts with ASK1- and CULLIN1
      like proteins in Antirrhinum, and together, they likely form an Skp1/Cullin or
      CDC53/F-box (SCF) complex. Third, compatible pollination was specifically blocked
      after the treatment of the proteasomal inhibitors MG115 and MG132, but they had
      little effect on incompatible pollination both in vitro and in vivo, indicating
      that the ubiquitin/26S proteasome activity is involved in compatible pollination.
      Fourth, the ubiquitination level of style proteins was increased substantially
      after compatible pollination compared with incompatible pollination, and
      coimmunoprecipitation revealed that S-RNases were ubiquitinated after incubating
      pollen proteins with compatible but not with incompatible style proteins,
      suggesting that non-self S-RNases are possibly degraded by the ubiquitin/26S
      proteasome pathway. Fifth, the S-RNase level appeared to be reduced after 36 h of
      compatible pollination. Taken together, these results show that AhSLF-S(2)
      interacts with S-RNases likely through a proposed SCF(AhSLF-S2) complex that
      targets S-RNase destruction during compatible rather than incompatible
      pollination, thus providing a biochemical basis for the inhibition of pollen tube
      growth as observed in self-incompatible response in Antirrhinum.

PMID- 14973169
TI  - The acyl-CoA synthetase encoded by LACS2 is essential for normal cuticle
      development in Arabidopsis.
AB  - Long-chain acyl-CoA synthetase (LACS) activities are encoded by a family of at
      least nine genes in Arabidopsis (Arabidopsis thaliana). These enzymes have roles
      in lipid synthesis, fatty acid catabolism, and the transport of fatty acids
      between subcellular compartments. Here, we show that the LACS2 gene (At1g49430)
      is expressed in young, rapidly expanding tissues, and in leaves expression is
      limited to cells of the adaxial and abaxial epidermal layers, suggesting that the
      LACS2 enzyme may act in the synthesis of cutin or cuticular waxes. A lacs2 null
      mutant was isolated by reverse genetics. Leaves of mutant plants supported pollen
      germination and released chlorophyll faster than wild-type leaves when immersed
      in 80% ethanol, indicating a defect in the cuticular barrier. The composition of
      surface waxes extracted from lacs2 leaves was similar to the wild type, and the
      total wax load was higher than the wild type (111.4 microg/dm(2) versus 76.4
      microg/dm(2), respectively). However, the thickness of the cutin layer on the
      abaxial surface of lacs2 leaves was only 22.3 +/- 1.7 nm compared with 33.0 +/-
      2.0 nm for the wild type. In vitro assays showed that 16-hydroxypalmitate was an
      excellent substrate for recombinant LACS2 enzyme. We conclude that the LACS2
      isozyme catalyzes the synthesis of omega-hydroxy fatty acyl-CoA intermediates in
      the pathway to cutin synthesis. The lacs2 phenotype, like the phenotypes of some
      other cutin mutants, is very pleiotropic, causing reduced leaf size and plant
      growth, reduced seed production, and lower rates of seedling germination and
      establishment. The LACS2 gene and the corresponding lacs2 mutant will help in
      future studies of the cutin synthesis pathway and in understanding the
      consequences of reduced cutin production on many aspects of plant biology.

PMID- 14973170
TI  - Protein phosphorylation in amyloplasts regulates starch branching enzyme activity
      and protein-protein interactions.
AB  - Protein phosphorylation in amyloplasts and chloroplasts of Triticum aestivum
      (wheat) was investigated after the incubation of intact plastids with gamma-(32)P
      ATP. Among the soluble phosphoproteins detected in plastids, three forms of
      starch branching enzyme (SBE) were phosphorylated in amyloplasts (SBEI, SBEIIa,
      and SBEIIb), and both forms of SBE in chloroplasts (SBEI and SBEIIa) were shown
      to be phosphorylated after sequencing of the immunoprecipitated (32)P-labeled
      phosphoproteins using quadrupole-orthogonal acceleration time of flight mass
      spectrometry. Phosphoamino acid analysis of the phosphorylated SBE forms
      indicated that the proteins are all phosphorylated on Ser residues. Analysis of
      starch granule-associated phosphoproteins after incubation of intact amyloplasts
      with gamma-(32)P-ATP indicated that the granule-associated forms of SBEII and two
      granule-associated forms of starch synthase (SS) are phosphorylated, including
      SSIIa. Measurement of SBE activity in amyloplasts and chloroplasts showed that
      phosphorylation activated SBEIIa (and SBEIIb in amyloplasts), whereas
      dephosphorylation using alkaline phosphatase reduced the catalytic activity of
      both enzymes. Phosphorylation and dephosphorylation had no effect on the
      measurable activity of SBEI in amyloplasts and chloroplasts, and the activities
      of both granule-bound forms of SBEII in amyloplasts were unaffected by
      dephosphorylation. Immunoprecipitation experiments using peptide-specific anti
      SBE antibodies showed that SBEIIb and starch phosphorylase each
      coimmunoprecipitated with SBEI in a phosphorylation-dependent manner, suggesting
      that these enzymes may form protein complexes within the amyloplast in vivo.
      Conversely, dephosphorylation of immunoprecipitated protein complex led to its
      disassembly. This article reports direct evidence that enzymes of starch
      metabolism (amylopectin synthesis) are regulated by protein phosphorylation and
      indicate a wider role for protein phosphorylation and protein-protein
      interactions in the control of starch anabolism and catabolism.

PMID- 14973172
TI  - Cerebrovascular responses in the fetal sheep brain to low-dose endotoxin.
AB  - Clinical and experimental evidence indicate that infection in pregnancy is
      associated with fetal brain damage. However, the inflammatory processes that
      compromise the fetal brain are not fully understood. In this study, we used a
      single, low dose of lipopolysaccharide (LPS, 0.1 microg/kg i.v.) to provoke an
      acute-phase response in unanesthetized fetal sheep in utero. COX-2 mRNA was
      increased in the cortex and cerebellum at 24 and 48 h after LPS, and
      immunoreactive COX-2 protein was increased in perivascular cells throughout gray
      and white matter at 24 h after LPS administration. Plasma albumin was observed in
      the parenchyma of the brain in cortex, thalamus, hypothalamus, corpus callosum,
      fornix, hippocampus, midbrain, subcallosal bundle, and cerebellar Purkinje cells.
      Large, rounded, lectin-positive cells with the appearance of macrophages were
      observed around blood vessels in subventricular white matter. These results
      indicate that blood-brain barrier permeability is increased in the fetal brain
      after exposure to endotoxin and suggests that cytotoxic and pro-inflammatory
      substances could pass from the circulation into the brain after peripheral
      inflammatory stimulation.

PMID- 14973171
TI  - The F-box protein ZEITLUPE confers dosage-dependent control on the circadian
      clock, photomorphogenesis, and flowering time.
AB  - As an F-box protein, ZEITLUPE (ZTL) is involved in targeting one or more
      substrates for ubiquitination and degradation via the proteasome. The initial
      characterization of ZTL suggested a function limited largely to the regulation of
      the circadian clock. Here, we show a considerably broader role for ZTL in the
      control of circadian period and photomorphogenesis. Using a ZTL-specific
      antibody, we quantitated and characterized a ZTL dosage series that ranges from a
      null mutation to a strong ZTL overexpressor. In the dark, ztl null mutations
      lengthen circadian period, and overexpression causes arrhythmicity, suggesting a
      more comprehensive role for this protein in the clock than previously suspected.
      In the light, circadian period becomes increasingly shorter at higher levels of
      ZTL, to the point of arrhythmicity. By contrast, hypocotyl length increases and
      flowering time is delayed in direct proportion to the level of ZTL. We propose a
      novel testable mechanism by which circadian period and amplitude may act together
      to gate phytochrome B-mediated suppression of hypocotyl. We also demonstrate that
      ZTL-dependent delay of flowering is mediated through decreases in CONSTANS and
      FLOWERING LOCUS T message levels, thus directly linking proteasome-dependent
      proteolysis to flowering.

PMID- 14973174
TI  - Impaired angiogenesis in the aged.
AB  - The process of angiogenesis, during which new blood vessels are formed, is
      impaired during aging. This Perspective describes many of the myriad components
      of the angiogenic response that are altered with age. In addition, the impact of
      impaired angiogenesis on wound healing, vascular disease, and cancer in the aged
      is discussed.

PMID- 14973173
TI  - Differentiated thyroid carcinomas from children and adolescents express IGF-I and
      the IGF-I receptor (IGF-I-R). Cancers with the most intense IGF-I-R expression
      may be more aggressive.
AB  - Adult thyroid cancers express IGF and IGF-I receptor (IGF-I-R), but the clinical
      impact is not clear. No previous study examined any childhood thyroid cancers
      that are well-differentiated and have a favorable prognosis. We used
      immunohistochemistry to determine IGF-I and IGF-I-R in 23 papillary thyroid
      cancers (PTC) and 6 follicular thyroid cancers (FTC) from children and
      adolescents. IGF-I was detected in 45% and IGF-I-R in 43% of cancers. IGF-I and
      IGF-I-R were found more often in PTC (IGF-I = 9/23, IGF-I-R = 8/19) than normal
      surrounding thyroid (IGF-I = 0/10, p = 0.032 and IGF-I-R = 0/10, p = 0.030).
      There were too few FTC to support independent statistical analysis, but IGF-I was
      found in 4 of 6 FTC (0/10 normal), and IGF-I-R was found in 2 of 4 FTC (0/10
      normal). IGF-I-R staining was more intense in aggressive (invasive, metastatic,
      recurrent, or persistent) than indolent tumors (confined to the gland, p =
      0.029). Over time, six tumors recurred, five of which expressed IGF-I-R. Overall
      recurrence risk was significantly greater for tumors that expressed IGF-I-R (p =
      0.05) but only approached statistical significance (p = 0.08) when disease-free
      survival was determined. We conclude that differentiated thyroid cancers of
      children and adolescents express IGF-I and IGF-I-R. Tumors that express IGF-I-R
      are more likely to show aggressive clinical features (invasion beyond the
      capsule, metastasis, or recurrence) and persistence despite treatment.

PMID- 14973175
TI  - Augmenting with amylin.

PMID- 14973176
TI  - Coagulation, inflammation, and the risk of neonatal white matter damage.
AB  - Indicators of coagulation activation are sometimes increased in the blood of
      newborns and adults who have a systemic inflammatory response. These coagulation
      factors have the ability to exacerbate inflammation, which in turn can promote
      coagulation. Therapies directed solely at coagulation factors and therapies
      directed solely at inflammation factors have not proved effective in reducing
      mortality in adults with a systemic inflammatory response syndrome and multi
      organ dysfunction (SIRS/MOD). On the other hand, the only therapy that has
      reduced mortality in SIRS/MOD is activated protein C, which has both anti
      coagulation and anti-inflammatory effects. This and other observations support
      the view that activated coagulation factors enhance inflammation. Since newborns
      at risk of cerebral white matter damage and cerebral palsy are more likely than
      their peers to have a systemic inflammatory response, which is sometimes
      accompanied by elevated blood levels of coagulation factors, we suggest that
      activated coagulation factors contribute to the occurrence of cerebral white
      matter damage by exacerbating inflammatory phenomena, rather than by occluding
      cerebral blood vessels.

PMID- 14973177
TI  - MMP-2 and MMP-9 and their tissue inhibitors in the plasma of preterm and term
      neonates.
AB  - Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are involved
      in a variety of physiologic growth and development and pathophysiologic
      inflammatory conditions. We hypothesized that 1) MMP-2 and -9 plasma activities
      and TIMP-1 and -2 plasma concentrations in preterm and term neonates were
      dependent on the gestational and postnatal age; and 2) the respective MMP and
      their inhibitors were deranged in the development of bronchopulmonary dysplasia
      (BPD) and intraventricular hemorrhage (IVH) in preterm neonates. From 1998 to
      1999, blood samples were collected from preterm neonates (25-36 wk gestation)
      with or without BPD and/or IVH as well as from healthy term (37-40 wk gestation)
      neonates during the first 28 d of life. MMP-2 and MMP-9 plasma activities were
      measured by zymography; TIMP-1 and TIMP-2 plasma concentrations were determined
      by ELISA. In neonates without BPD or IVH (n = 50), MMP-2 and MMP-9 plasma
      activities both appeared to be gestational age dependent, with the highest levels
      observed in neonates of 33-36 wk gestation. TIMP-1 plasma concentration was
      highest in term neonates but no gestational difference was found in TIMP-2. Only
      MMP-9 showed a 50% decrease after d 1 in the first postnatal month. Twelve
      preterm infants with BPD and/or IVH had significantly lower MMP-2 but higher MMP
      9 activity and higher TIMP-1 concentration than those of corresponding neonates
      without BPD or IVH. These findings show the gestational age-dependent expression
      of plasma MMP activities and their inhibitors. MMP and TIMP may be involved in
      the feto-neonatal development and may contribute to the pathogenesis of BPD
      and/or IVH in critically ill preterm neonates.

PMID- 14973179
TI  - Nephron endowment and filtration surface area in the kidney after growth
      restriction of fetal sheep.
AB  - Low birth weight is associated with adult-onset diseases including hypertension
      and renal disease; altered renal development after intrauterine growth
      restriction (IUGR) may underlie such prenatal programming. Our aim was to
      investigate nephron endowment and renal filtration surface area in fetal sheep in
      which IUGR resulted from late gestational umbilico-placental embolization (UPE)
      or natural twinning. UPE was performed between 120 and 140 d of gestation (term
      approximately 147 d). At autopsy (140 d), body weights of UPE and twin fetuses
      were, respectively, 34% and 28% lower than controls. Kidneys were sampled using a
      smooth fractionator approach and glomerular number was estimated using a physical
      disector/fractionator technique. Glomerular capillary length and filtration
      surface area were estimated using unbiased stereological techniques. Although
      relative kidney weights (grams per kilogram body weight) were not different
      between groups, nephron endowment was 40% lower in twin fetuses compared with
      controls (34.3 +/- 10.6 x 10(4) and 55.9 +/- 19.8 x 10(4), respectively; p <
      0.05); UPE did not alter nephron number (50.7 +/- 13.2 x 10(4)). There was no
      difference in the glomerular capillary length or surface area between the UPE and
      control fetuses. IUGR due to twinning leads to reduced nephron endowment whereas
      late gestational IUGR does not, suggesting that reduced nephron endowment is
      dependent on the timing of the growth restriction. Our findings demonstrate that
      reduced birth weight per se does not necessarily imply reduced nephron endowment.

PMID- 14973178
TI  - Developmental regulation of galactokinase in suckling mouse liver by the Egr-1
      transcription factor.
AB  - The numerous changes in metabolic pathways that accompany liver development
      entail associated changes in gene expression. Egr-1 is a zinc-finger
      transcription factor that regulates genes involved in cellular growth,
      differentiation, stress response, and apoptosis in many cell types. Egr-1 is
      induced in liver regeneration in rodents, but its role in normal hepatocyte
      function has not been characterized. We examined the developmental expression of
      Egr-1 in mouse liver and found that its expression increased during the suckling
      period. In screening the sequences of the genes involved in lactose assimilation,
      we found that the galactokinase gene Glk contains four potential Egr-1 binding
      sites in its proximal promoter. A minimal promoter of 155 nucleotides
      encompassing the four Egr-1 sites exhibited activity in hepatoma cell lines by
      transient transfection assays. Moreover, co-transfection of an Egr-1 expression
      plasmid increased promoter activity. Finally, mutations introduced into three of
      the four Egr-1 binding sites decreased activity, whereas mutation of the
      remaining site increased promoter activity. These data tie Egr-1 and
      galactokinase together in a developmentally regulated chain to prepare the
      neonate for suckling.

PMID- 14973180
TI  - Diurnal fluctuation of leukocyte G6PD activity. A possible explanation for the
      normal neutrophil bactericidal activity and the low incidence of pyogenic
      infections in patients with severe G6PD deficiency in Israel.
AB  - Acute hemolytic anemia associated with red blood cell (RBC) glucose-6-phosphate
      dehydrogenase (G6PD) deficiency is commonly encountered in the Mediterranean
      basin. Nevertheless, concomitant clinical evidence of white blood cell G6PD
      deficiency is extremely rare in Israel. This study sought to assess
      simultaneously levels of G6PD activity in polymorphonuclear leukocytes (PMN) and
      in red blood cells (RBC) of patients with G6PD deficiency, including full-term
      newborn infants. In PMN, the correlation between G6PD activity, hexose
      monophosphate shunt activity, and superoxide anion release was evaluated. In G6PD
      deficient patients, a parallel and significantly decreased G6PD activity was
      found in neutrophils (range of activity 0-4.5 IU/10(6) PMN) and erythrocytes
      (range of activity 0-1.8 IU/g Hb), compared with healthy controls (5-23 IU/10(6)
      PMN and 2.4-6.4 IU/g Hb, respectively). A positive correlation was found in PMN
      between the levels of G6PD activity, hexose monophosphate (HMP) shunt activity,
      and superoxide anion release (p < 0.01). Nevertheless, all patients' bactericidal
      activity of neutrophils remained in the range of healthy controls. Although many
      episodes of acute hemolytic anemia were recorded, no increased incidence of
      pyogenic infections was observed in any group of patients investigated.
      Neutrophil and erythrocyte G6PD levels were re-assessed in some of these patients
      several times a day. A significant diurnal fluctuation of the enzyme activity was
      found. It is speculated that the patients produce fluctuating daily quantities of
      NADPH, sufficient to initiate the neutrophil respiratory burst and to achieve
      normal bactericidal activity, necessary to prevent the development of microbial
      infections.

PMID- 14973181
TI  - Response of circulating ghrelin levels to insulin therapy in children with newly
      diagnosed type 1 diabetes mellitus.
AB  - Ghrelin is secreted primarily by the stomach, although other tissues such as the
      pancreas synthesize a minor proportion. The discovery of a new cell type that
      produces ghrelin in the human pancreas and that this organ expresses GHS-R opens
      new perspectives in the understanding of the control of glucose metabolism. We
      have studied 22 children with newly diagnosed type 1 diabetes mellitus at four
      different points: at diagnosis before insulin therapy, after 48-60 h of insulin
      therapy, and after 1 and 4 mo of insulin treatment. At each point circulating
      levels of ghrelin, leptin, IGF-I, IGF binding protein (IGFBP)-1, IGFBP-2, IGFBP
      3, and glucose were determined. Ghrelin levels were significantly decreased at
      diagnosis (573 +/- 68 pg/mL, p < 0.01) compared with controls (867 +/- 38 pg/mL)
      and remained decreased after insulin therapy (d 2: 595 +/- 68 pg/mL; 1 mo: 590 +/
      61 pg/mL; 4 mo: 538 +/- 67 pg/mL) with no differences before or after insulin
      treatment. There was a negative correlation between ghrelin levels and body mass
      index at all of the study points, whereas a negative correlation between ghrelin
      and glucose concentrations was only observed after insulin therapy. No
      correlation between ghrelin and HbA1c was found at any point. A positive
      correlation between ghrelin and IGFBP-1 was found after insulin therapy, but no
      correlation with other members of the IGF system or leptin was found. In
      conclusion, these data could indicate a possible link between glucose
      concentrations and ghrelin; hence, the persisting low ghrelin levels in diabetic
      children may suggest a defensive mechanism against hyperglycemia.

PMID- 14973182
TI  - Antenatal betamethasone changes cord blood monocyte responses to endotoxin in
      preterm lambs.
AB  - Corticosteroids are routinely administered to women at risk for preterm delivery
      to induce fetal lung maturation. Antenatal corticosteroids have immunomodulatory
      effects on fetal immune cells that are poorly understood. We hypothesized that
      maternal betamethasone would alter in fetal monocytes both the initiation of
      inflammation in response to pro-inflammatory stimuli and the resolution of
      inflammation by phagocytosis of apoptotic neutrophils. Preterm lambs at 124 d
      gestation were delivered 15 h, 1 d, 2 d, or 7 d after 0.5 mg/kg maternal
      intramuscular betamethasone. Monocytes from cord blood were isolated and cultured
      and results were compared with monocytes from preterm lambs exposed to maternal
      saline or monocytes from adult sheep. Phagocytosis of Escherichia coli was not
      changed, however, phagocytosis of apoptotic neutrophils was low in fetal
      monocytes but increased after 7 d exposure to maternal betamethasone to the level
      found in adult monocytes. Hydrogen peroxide production after endotoxin stimulus
      was significantly reduced to 7.1 +/- 2.2 micromol at 5 h, 8.7 +/- 2.9 micromol at
      24 h, and 4.1 +/- 1.9 micromol at 48 h versus 16.4 +/- 3.6 micromol in control
      animals; at 7 d, the hydrogen peroxide production increased to 74.3 +/- 19.7
      micromol (p < 0.05, per 10(6) monocytes). IL-6 production was reduced at 15 h
      after maternal betamethasone but at no other time point. Maternal betamethasone
      initially suppressed several fetal monocyte functions, however, at 7 d,
      measurements of initiation and resolution of inflammation were increased to
      levels similar to monocytes from adult sheep. The time-dependent changes in
      maternal betamethasone modulation of the responses of fetal monocytes may
      influence immune function of the preterm lamb after delivery.

PMID- 14973183
TI  - I regret that I have but one life to give for my colony. Aging yeast commit
      suicide to save neighbors.

PMID- 14973184
TI  - Activation of the Wnt signaling pathway in chronic lymphocytic leukemia.
AB  - B cell chronic lymphocytic leukemia (CLL) is characterized by an accumulation of
      mature, functionally incompetent B cells. Wnts are a large family of secreted
      glycoproteins involved in cell proliferation, differentiation, and oncogenesis.
      The classical Wnt signaling cascade inhibits the activity of the enzyme glycogen
      synthase kinase-3beta, augmenting beta-catenin translocation to the nucleus, and
      the transcription of target genes. Little is known about the potential roles of
      Wnt signaling in CLL. In this study, we quantified the gene expression profiles
      of the Wnt family, and their cognate frizzled (Fzd) receptors in primary CLL
      cells, and determined the role of Wnt signaling in promoting CLL cell survival.
      Wnt3, Wnt5b, Wnt6, Wnt10a, Wnt14, and Wnt16, as well as the Wnt receptor Fzd3,
      were highly expressed in CLL, compared with normal B cells. Three lines of
      evidence suggested that the Wnt signaling pathway was active in CLL. First, the
      Wnt/beta-catenin-regulated transcription factor lymphoid-enhancing factor-1, and
      its downstream target cyclin D1, were overexpressed in CLL. Second, a
      pharmacological inhibitor of glycogen synthase kinase-3 beta, SB-216763,
      activated beta-catenin-mediated transcription, and enhanced the survival of CLL
      lymphocytes. Third, Wnt/beta-catenin signaling was diminished by an analog of a
      nonsteroidal antiinflammatory drug (R-etodolac), at concentrations that increased
      apoptosis of CLL cells. Taken together, these results indicate that Wnt signaling
      genes are overexpressed and are active in CLL. Uncontrolled Wnt signaling may
      contribute to the defect in apoptosis that characterizes this malignancy.

PMID- 14973185
TI  - Adaptive role of increased frequency of polypurine tracts in mRNA sequences of
      thermophilic prokaryotes.
AB  - The mechanism of an organism's adaptation to high temperatures has been
      investigated intensively in recent years. It was suggested that the
      macromolecules of thermophilic microorganisms (especially proteins) have
      structural features that enhance their thermostability. We compared mRNA
      sequences of 72 fully sequenced prokaryotic proteomes (14 thermophilic and 58
      mesophilic species). Although the differences between the percentage of adenine
      plus guanine content of whole mRNAs of different prokaryotic species are much
      lower than those of guanine plus cytosine content, the thermophile purine
      pyrimidine (R/Y) ratio within their mRNAs is significantly higher than that of
      the mesophiles. The first and third codon positions of both thermophiles and
      mesophiles are purine-biased, with the bias more pronounced by the thermophiles.
      Thermophile mRNAs that display the highest R/Y ratio (1.43-1.69) are those of the
      ribosomal proteins, histone-like proteins, DNA-dependent RNA polymerase subunits,
      and heat-shock proteins. Within mesophilic prokaryotes and five eukaryotic
      species, the R/Y ratio of the mRNAs of heat-shock proteins is higher than their
      average over coding part of the genome. Polypurine tracts (R)(n) (with n > or =
      5) are much more abundant within the thermophile mRNAs compared with mesophiles.
      Between two sequential pure-purinic codons of thermophile mRNAs, there is a
      rather strong tendency for the occurrence of adenine but not guanine tracts. The
      data suggest that mixed adenine.guanine and polyadenine tracts in mRNAs increase
      the thermostability beyond the contribution of amino acids encoded by purine
      tracts, which highlights the importance of ecological stress in the evolution of
      genome architecture.

PMID- 14973186
TI  - Spontaneous nucleotide exchange in low molecular weight GTPases by fluorescently
      labeled gamma-phosphate-linked GTP analogs.
AB  - Regulated guanosine nucleotide exchange and hydrolysis constitute the fundamental
      activities of low molecular weight GTPases. We show that three guanosine 5'
      triphosphate analogs with BODIPY fluorophores coupled via the gamma phosphate
      bind to the GTPases Cdc42, Rac1, RhoA, and Ras and displace guanosine 5'
      diphosphate with high intrinsic exchange rates in the presence of Mg(2+) ions,
      thereby acting as synthetic, low molecular weight guanine nucleotide exchange
      factors. The accompanying large fluorescence enhancements (as high as 12-fold),
      caused by a reduction in guanine quenching of the environmentally sensitive
      BODIPY dye fluorescence on protein binding, allow for real-time monitoring of
      this spontaneous nucleotide exchange in the visible spectrum with high signal-to
      noise ratios. Binding affinities increased with longer aliphatic linkers
      connecting the nucleotide and BODIPY fluorophore and were in the 10-100 nM range.
      Steady-state and time-resolved fluorescence spectroscopy showed an inverse
      relationship between linker length and fluorescence enhancement factors and
      differences in protein-bound fluorophore mobilities, providing optimization
      criteria for future applications of such compounds as efficient elicitors and
      reporters of nucleotide exchange. EDTA markedly enhanced nucleotide exchange,
      enabling rapid loading of GTPases with these probes. Differences in active site
      geometries, in the absence of Mg(2+), caused qualitatively different reporting of
      the bound state by the different analogs. The BODIPY analogs also prevented the
      interaction of Cdc42 with p21 activated kinase. Together, these results validate
      the use of these analogs as valuable tools for studying GTPase functions and for
      developing potent synthetic nucleotide exchange factors for this important class
      of signaling molecules.

PMID- 14973187
TI  - The SPANX gene family of cancer/testis-specific antigens: rapid evolution and
      amplification in African great apes and hominids.
AB  - Human sperm protein associated with the nucleus on the X chromosome (SPANX) genes
      comprise a gene family with five known members (SPANX-A1, -A2, -B, -C, and -D),
      encoding cancer/testis-specific antigens that are potential targets for cancer
      immunotherapy. These highly similar paralogous genes cluster on the X chromosome
      at Xq27. We isolated and sequenced primate genomic clones homologous to human
      SPANX. Analysis of these clones and search of the human genome sequence revealed
      an uncharacterized group of genes, SPANX-N, which are present in all primates as
      well as in mouse and rat. In humans, four SPANX-N genes comprise a series of
      tandem duplicates at Xq27; a fifth member of this subfamily is located at Xp11.
      Similarly to SPANX-A/D, human SPANX-N genes are expressed in normal testis and
      some melanoma cell lines; testis-specific expression of SPANX is also conserved
      in mouse. Analysis of the taxonomic distribution of the long and short forms of
      the intron indicates that SPANX-N is the ancestral form, from which the SPANX-A/D
      subfamily evolved in the common ancestor of the hominoid lineage. Strikingly, the
      coding sequences of the SPANX genes evolved much faster than the intron and the
      5' untranslated region. There is a strong correlation between the rates of
      evolution of synonymous and nonsynonymous codon positions, both of which are
      accelerated 2-fold or more compared to the noncoding sequences. Thus, evolution
      of the SPANX family appears to have involved positive selection that affected not
      only the protein sequence but also the synonymous sites in the coding sequence.

PMID- 14973188
TI  - Global analysis of nutrient control of gene expression in Saccharomyces
      cerevisiae during growth and starvation.
AB  - Global gene expression in yeast was examined in five different nutrient-limited
      steady states and in their corresponding starvation-induced stationary phases.
      The use of chemostats, with their ability to generate defined and reproducible
      physiological conditions, permitted the exclusion of the confounding variables
      that frequently complicate transcriptome analyses. This approach allowed us to
      dissect out effects on gene expression that are specific to particular
      physiological states. Thus, we discovered that a large number of ORFs involved in
      protein synthesis were activated under ammonium limitation, whereas the
      expression of ORFs concerned with energy and metabolism was enhanced by carbon
      limitation. Elevated transcription of genes in high-affinity glucose uptake, the
      trichloroacetic acid cycle, and oxidative phosphorylation were observed in
      glucose-limiting, but not glucose-abundant, conditions. In contrast, genes
      involved in gluconeogenesis and, interestingly, genes subject to nitrogen
      catabolite repression increased their transcription when ethanol was the carbon
      source, even though ammonium was in excess. This result suggests that up
      regulation of genes sensitive to nitrogen catabolite repression may contribute
      anapleurotic intermediates in ethanol-grown cells. The different starvation
      conditions produced two general types of transcription profiles, with carbon
      starved cells transcribing far fewer genes than cells starved for any of the
      other macronutrients. Nonetheless, each starvation condition induced its own
      peculiar set of genes, and only 17 genes were induced >5-fold by all five
      starvations. In all cases, analysis of the upstream sequences of clusters of
      coregulated genes identified motifs that may be recognized by transcription
      factors specific for controlling gene expression in each of the physiological
      conditions examined.

PMID- 14973189
TI  - Nuclear localization and molecular partners of BIG1, a brefeldin A-inhibited
      guanine nucleotide-exchange protein for ADP-ribosylation factors.
AB  - Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) is an
      approximately 200-kDa brefeldin A-inhibited guanine nucleotide-exchange protein
      that preferentially activates ADP-ribosylation factor 1 (ARF1) and ARF3. BIG1 was
      found in cytosol in a multiprotein complex with a similar ARF-activating protein,
      BIG2, which is also an A kinase-anchoring protein. In HepG2 cells growing with
      serum, BIG1 was primarily cytosolic and Golgi-associated. After incubation
      overnight without serum, a large fraction of endogenous BIG1 was in the nuclei.
      By confocal immunofluorescence microscopy, BIG1 was localized with nucleoporin
      p62 at the nuclear envelope (probably during nucleocytoplasmic transport) and
      also in nucleoli, clearly visible against the less concentrated overall matrix
      staining. BIG1 was also identified by Western blot analyses in purified
      subnuclear fractions (e.g., nucleoli and nuclear matrix). Antibodies against
      BIG1, nucleoporin, or nucleolin coimmunoprecipitated the other two proteins from
      purified nuclei. In contrast, BIG2 was not associated with nuclear BIG1. Also of
      note, ARF was never detected among proteins precipitated from purified nuclei by
      anti-BIG1 antibodies, although microscopically the two proteins do appear
      sometimes to be colocalized in the nucleus. These data are consistent with
      independent intracellular movements and actions of BIG1 and BIG2, and they are
      also evidence of the participation of BIG1 in both Golgi and nuclear functions.

PMID- 14973190
TI  - Mitotic and neurogenic effects of dehydroepiandrosterone (DHEA) on human neural
      stem cell cultures derived from the fetal cortex.
AB  - Dehydroepiandrosterone (DHEA) is a neurosteroid with potential effects on
      neurogenesis and neuronal survival in humans. However, most studies on DHEA have
      been performed in rodents, and there is little direct evidence for biological
      effects on the human nervous system. Furthermore, the mechanism of its action is
      unknown. Here, we show that DHEA significantly increased the growth rates of
      human neural stem cells derived from the fetal cortex and grown with both
      epidermal growth factor (EGF) and leukemia inhibitory factor (LIF). However, it
      had no effect on cultures grown in either factor alone, suggesting a specific
      action on the EGF/LIF-responsive cell. Precursors of DHEA such as pregnenolone or
      six of its major metabolites, had no significant effect on proliferation rates.
      DHEA did not alter the small number (<3%) of newly formed neuroblasts or the
      large number (>95%) of nestin-positive precursors. However, the number of glial
      fibrillary acidic protein-positive cells, its mRNA, and protein were
      significantly increased by DHEA. We found both N-methyl-d-aspartate and sigma 1
      antagonists, but not GABA antagonists, could completely eliminate the effects of
      DHEA on stem cell proliferation. Finally we asked whether the EGF/LIF/DHEA
      responsive stem cells had an increased potential for neurogenesis and found a 29%
      increase in neuronal production when compared to cultures grown in EGF/LIF alone.
      Together these data suggest that DHEA is involved in the maintenance and division
      of human neural stem cells. Given the wide availability of this neurosteroid,
      this finding has important implications for future use.

PMID- 14973191
TI  - Human microRNA genes are frequently located at fragile sites and genomic regions
      involved in cancers.
AB  - A large number of tiny noncoding RNAs have been cloned and named microRNAs
      (miRs). Recently, we have reported that miR-15a and miR-16a, located at 13q14,
      are frequently deleted and/or down-regulated in patients with B cell chronic
      lymphocytic leukemia, a disorder characterized by increased survival. To further
      investigate the possible involvement of miRs in human cancers on a genome-wide
      basis, we have mapped 186 miRs and compared their location to the location of
      previous reported nonrandom genetic alterations. Here, we show that miR genes are
      frequently located at fragile sites, as well as in minimal regions of loss of
      heterozygosity, minimal regions of amplification (minimal amplicons), or common
      breakpoint regions. Overall, 98 of 186 (52.5%) of miR genes are in cancer
      associated genomic regions or in fragile sites. Moreover, by Northern blotting,
      we have shown that several miRs located in deleted regions have low levels of
      expression in cancer samples. These data provide a catalog of miR genes that may
      have roles in cancer and argue that the full complement of miRs in a genome may
      be extensively involved in cancers.

PMID- 14973192
TI  - FRIGIDA-related genes are required for the winter-annual habit in Arabidopsis.
AB  - In temperate climates, the prolonged cold temperature of winter serves as a
      seasonal landmark for winter-annual and biennial plants. In these plants,
      flowering is blocked before winter. In Arabidopsis thaliana, natural variation in
      the FRIGIDA (FRI) gene is a major determinate of the rapid-cycling vs. winter
      annual flowering habits. In winter-annual accessions of Arabidopsis, FRI activity
      blocks flowering through the up-regulation of the floral inhibitor FLOWERING
      LOCUS C (FLC). Most rapid-flowering accessions, in contrast, contain null alleles
      of FRI. By performing a mutant screen in a winter-annual strain, we have
      identified a locus, FRIGIDA LIKE 1 (FRL1), that is specifically required for the
      up-regulation of FLC by FRI. Cloning of FRL1 revealed a gene with a predicted
      protein sequence that is 23% identical to FRI. Despite sequence similarity, FRI
      and FRL1 do not have redundant functions. FRI and FRL1 belong to a seven-member
      gene family in Arabidopsis, and FRI, FRL1, and at least one additional family
      member, FRIGIDA LIKE 2 (FRL2), are in a clade of this family that is required for
      the winter-annual habit in Arabidopsis.

PMID- 14973193
TI  - Copper-induced ferroportin-1 expression in J774 macrophages is associated with
      increased iron efflux.
AB  - Copper is known to play a role in iron recycling from macrophages. To examine
      whether cellular copper status affects expression of the iron exporter
      ferroportin-1 (FPN1), J774 macrophage cells were exposed to 10-100 microM CuSO(4)
      for up to 20 h. Copper treatment significantly increased FPN1 mRNA in a dose- and
      time-dependent manner. After 20 h, 100 microM CuSO(4) up-regulated FPN1
      transcript levels approximately 13-fold compared to untreated controls. Induction
      was detected 8 h after copper treatment was initiated and markedly increased
      thereafter. A corresponding increase in FPN1 protein levels was observed upon
      copper treatment. Induction of J774 cell FPN1 expression by copper was also
      associated with a dose-dependent increase in (59)Fe release after
      erythrophagocytosis of labeled red blood cells. Thus, a previously
      uncharacterized role for copper in the regulation of macrophage iron recycling is
      suggested by the induction of FPN1 gene expression and iron efflux by this metal.

PMID- 14973194
TI  - The MafA transcription factor appears to be responsible for tissue-specific
      expression of insulin.
AB  - Insulin gene expression is regulated by several islet-enriched transcription
      factors. However, MafA is the only beta cell-specific activator. Here, we show
      that MafA selectively induces endogenous insulin transcription in non-beta cells.
      MafA was also first detected in the insulin-producing cells formed during the
      second and predominant phase of beta cell differentiation, and absent in the few
      insulin-positive cells found in Nkx6.1(-/-) pancreata, which lack the majority of
      second-phase beta cells. These results demonstrate that MafA is a potent insulin
      activator that is likely to function downstream of Nkx6.1 during islet insulin
      producing cell development.

PMID- 14973195
TI  - Portability and fidelity of RNA-repair systems.
AB  - Yeast tRNA ligase (Trl1) is an essential enzyme that converts cleaved tRNA half
      molecules into spliced tRNAs containing a 2'-PO(4), 3'-5' phosphodiester at the
      splice junction. Trl1 also catalyzes splicing of HAC1 mRNA during the unfolded
      protein response. Trl1 performs three reactions: the 2',3'-cyclic phosphate of
      the proximal RNA fragment is hydrolyzed to a 3'-OH, 2'-PO(4) by a cyclic
      phosphodiesterase; the 5'-OH of the distal RNA fragment is phosphorylated by a
      GTP-dependent polynucleotide kinase; and the 3'-OH, 2'-PO(4), and 5'-PO(4) ends
      are then sealed by an ATP-dependent RNA ligase. The removal of the 2'-PO(4) at
      the splice junction is catalyzed by the essential enzyme Tpt1, which transfers
      the RNA 2'-PO(4) to NAD(+) to form ADP-ribose 1"-2"-cyclic phosphate. Here, we
      show that the bacteriophage T4 enzymes RNA ligase 1 and polynucleotide
      kinase/phosphatase can fulfill the tRNA and HAC1 mRNA splicing functions of yeast
      Trl1 in vivo and bypass the requirement for Tpt1. These results attest to the
      portability of RNA-repair systems, notwithstanding the significant differences in
      the specificities, mechanisms, and reaction intermediates of the individual yeast
      and T4 enzymes responsible for the RNA healing and sealing steps. We surmise that
      Tpt1 and its unique metabolite ADP-ribose 1"-2"-cyclic phosphate do not play
      essential roles in yeast independent of the tRNA-splicing reaction. Our finding
      that one-sixth of spliced HAC1 mRNAs in yeast cells containing the T4 RNA-repair
      system suffered deletion of a single nucleotide at the 3' end of the splice-donor
      site suggests a model whereby the yeast RNA-repair system evolved a requirement
      for the 2'-PO(4) for RNA ligation to suppress inappropriate RNA recombination.

PMID- 14973196
TI  - Gene transfer in the evolution of parasite nucleotide biosynthesis.
AB  - Nucleotide metabolic pathways provide numerous successful targets for
      antiparasitic chemotherapy, but the human pathogen Cryptosporidium parvum thus
      far has proved extraordinarily refractory to classical treatments. Given the
      importance of this protist as an opportunistic pathogen afflicting
      immunosuppressed individuals, effective treatments are urgently needed. The
      genome sequence of C. parvum is approaching completion, and we have used this
      resource to critically assess nucleotide biosynthesis as a target in C. parvum.
      Genomic analysis indicates that this parasite is entirely dependent on salvage
      from the host for its purines and pyrimidines. Metabolic pathway reconstruction
      and experimental validation in the laboratory further suggest that the loss of
      pyrimidine de novo synthesis is compensated for by possession of three salvage
      enzymes. Two of these, uridine kinase-uracil phosphoribosyltransferase and
      thymidine kinase, are unique to C. parvum within the phylum Apicomplexa.
      Phylogenetic analysis suggests horizontal gene transfer of thymidine kinase from
      a proteobacterium. We further show that the purine metabolism in C. parvum
      follows a highly streamlined pathway. Salvage of adenosine provides C. parvum's
      sole source of purines. This renders the parasite susceptible to inhibition of
      inosine monophosphate dehydrogenase, the rate-limiting enzyme in the multistep
      conversion of AMP to GMP. The inosine 5' monophosphate dehydrogenase inhibitors
      ribavirin and mycophenolic acid, which are already in clinical use, show
      pronounced anticryptosporidial activity. Taken together, these data help to
      explain why widely used drugs fail in the treatment of cryptosporidiosis and
      suggest more promising targets.

PMID- 14973197
TI  - Revealing modularity and organization in the yeast molecular network by
      integrated analysis of highly heterogeneous genomewide data.
AB  - The dissection of complex biological systems is a challenging task, made
      difficult by the size of the underlying molecular network and the heterogeneous
      nature of the control mechanisms involved. Novel high-throughput techniques are
      generating massive data sets on various aspects of such systems. Here, we perform
      analysis of a highly diverse collection of genomewide data sets, including gene
      expression, protein interactions, growth phenotype data, and transcription factor
      binding, to reveal the modular organization of the yeast system. By integrating
      experimental data of heterogeneous sources and types, we are able to perform
      analysis on a much broader scope than previous studies. At the core of our
      methodology is the ability to identify modules, namely, groups of genes with
      statistically significant correlated behavior across diverse data sources.
      Numerous biological processes are revealed through these modules, which also obey
      global hierarchical organization. We use the identified modules to study the
      yeast transcriptional network and predict the function of >800 uncharacterized
      genes. Our analysis framework, SAMBA (Statistical-Algorithmic Method for
      Bicluster Analysis), enables the processing of current and future sources of
      biological information and is readily extendable to experimental techniques and
      higher organisms.

PMID- 14973198
TI  - Trends between gene content and genome size in prokaryotic species with larger
      genomes.
AB  - Although the evolution process and ecological benefits of symbiotic species with
      small genomes are well understood, these issues remain poorly elucidated for free
      living species with large genomes. We have compared 115 completed prokaryotic
      genomes by using the Clusters of Orthologous Groups database to determine whether
      there are changes with genome size in the proportion of the genome attributable
      to particular cellular processes, because this may reflect both cellular and
      ecological strategies associated with genome expansion. We found that large
      genomes are disproportionately enriched in regulation and secondary metabolism
      genes and depleted in protein translation, DNA replication, cell division, and
      nucleotide metabolism genes compared to medium- and small-sized genomes.
      Furthermore, large genomes do not accumulate noncoding DNA or hypothetical ORFs,
      because the portion of the genome devoted to these functions remained constant
      with genome size. Traits other than genome size or strain-specific processes are
      reflected by the dispersion around the mean for cell functions that showed no
      correlation with genome size. For example, Archaea had significantly more genes
      in energy production, coenzyme metabolism, and the poorly characterized category,
      and fewer in cell membrane biogenesis and carbohydrate metabolism than Bacteria.
      The trends we noted with genome size by using Clusters of Orthologous Groups were
      confirmed by our independent analysis with The Institute for Genomic Research's
      Comprehensive Microbial Resource and Kyoto Encyclopedia of Genes and Genomes'
      Orthology annotation databases. These trends suggest that larger genome-sized
      species may dominate in environments where resources are scarce but diverse and
      where there is little penalty for slow growth, such as soil.

PMID- 14973199
TI  - Reduced inflammatory hyperalgesia with preservation of acute thermal nociception
      in mice lacking cGMP-dependent protein kinase I.
AB  - cGMP-dependent protein kinase I (PKG-I) has been suggested to contribute to the
      facilitation of nociceptive transmission in the spinal cord presumably by acting
      as a downstream target of nitric oxide. However, PKG-I activators caused
      conflicting effects on nociceptive behavior. In the present study we used PKG-I(
      /-) mice to further assess the role of PKG-I in nociception. PKG-I deficiency was
      associated with reduced nociceptive behavior in the formalin assay and zymosan
      induced paw inflammation. However, acute thermal nociception in the hot-plate
      test was unaltered. After spinal delivery of the PKG inhibitor, Rp-8-Br-cGMPS,
      nociceptive behavior of PKG-I(+/+) mice was indistinguishable from that of PKG-I(
      /-) mice. On the other hand, the PKG activator, 8-Br-cGMP (250 nmol
      intrathecally) caused mechanical allodynia only in PKG-I(+/+) mice, indicating
      that the presence of PKG-I was essential for this effect. Immunofluorescence
      studies of the spinal cord revealed additional morphological differences. In the
      dorsal horn of 3- to 4-week-old PKG-I(-/-) mice laminae I-III were smaller and
      contained fewer neurons than controls. Furthermore, the density of substance P
      positive neurons and fibers was significantly reduced. The paucity of substance P
      in laminae I-III may contribute to the reduction of nociception in PKG-I(-/-)
      mice and suggests a role of PKG-I in substance P synthesis.

PMID- 14973200
TI  - A gene-specific DNA sequencing chip for exploring molecular evolutionary change.
AB  - Sequencing by hybridization (SBH) approaches to DNA sequencing face two
      conflicting constraints. First, in order to ensure that the target DNA binds
      reliably, the oligonucleotide probes that are attached to the chip array must be
      >15 bp in length. Secondly, the total number of possible 15 bp oligonucleotides
      is too large (>4(15)) to fit on a chip with current technology. To circumvent the
      conflict between these two opposing constraints, we present a novel gene-specific
      DNA chip design. Our design is based on the idea that not all conceivable
      oligonucleotides need to be placed on a chip--only those that capture sequence
      combinations occurring in nature. Our approach uses a training set of aligned
      sequences that code for the gene in question. We compute the minimum number of
      oligonucleotides (generally 15-30 bp in length) that need to be placed on a DNA
      chip to capture the variation implied by the training set using a graph search
      algorithm. We tested the approach in silico using cytochrome-b sequences. Results
      indicate that on average, 98% of the sequence of an unknown target can be
      determined using the approach.

PMID- 14973202
TI  - Images in clinical medicine. Meckel's diverticulum in action.

PMID- 14973201
TI  - A novel strategy to engineer DNA polymerases for enhanced processivity and
      improved performance in vitro.
AB  - Mechanisms that allow replicative DNA polymerases to attain high processivity are
      often specific to a given polymerase and cannot be generalized to others. Here we
      report a protein engineering-based approach to significantly improve the
      processivity of DNA polymerases by covalently linking the polymerase domain to a
      sequence non-specific dsDNA binding protein. Using Sso7d from Sulfolobus
      solfataricus as the DNA binding protein, we demonstrate that the processivity of
      both family A and family B polymerases can be significantly enhanced. By
      introducing point mutations in Sso7d, we show that the dsDNA binding property of
      Sso7d is essential for the enhancement. We present evidence supporting two novel
      conclusions. First, the fusion of a heterologous dsDNA binding protein to a
      polymerase can increase processivity without compromising catalytic activity and
      enzyme stability. Second, polymerase processivity is limiting for the efficiency
      of PCR, such that the fusion enzymes exhibit profound advantages over unmodified
      enzymes in PCR applications. This technology has the potential to broadly improve
      the performance of nucleic acid modifying enzymes.

PMID- 14973203
TI  - Delineation of the mechanisms of aberrant splicing caused by two unusual intronic
      mutations in the RSK2 gene involved in Coffin-Lowry syndrome.
AB  - Coffin-Lowry syndrome (CLS) is caused by mutations in the RSK2 gene encoding a
      protein kinase of the Ras signalling pathway. We have studied two point mutations
      which cause aberrant splicing but do not concern the invariant GT or AG
      nucleotides of splice sites. The first, an A-->G transition at position +3 of the
      5' splice site of exon 6, results in vivo and in vitro in exon skipping and
      premature translation termination. The natural 5' splice site, although
      intrinsically weak, is not transactivated under normal conditions. Consequently,
      replacement of an A/U by a G/U base pairing with U1 snRNA reduces its strength
      below a critical threshold. The second mutation, an A-->G transition 11 nt
      upstream of exon 5, creates a new AG near the natural 3' splice site. In vitro
      this synthetic 3' AG is used exclusively by the splicing machinery. In vivo this
      splicing event is also observed, but is underestimated because the resulting RSK2
      mRNA contains premature stop codons which trigger the nonsense-mediated decay
      process. We show that a particular mechanism is involved in the aberrant splicing
      of exon 5, implying involvement of the natural 3' AG during the first catalytic
      step and the new 3' AG during the second step. Thus, our results explain how
      these mutations cause severe forms of CLS.

PMID- 14973204
TI  - Diffuse small-bowel myelomatosis.

PMID- 14973205
TI  - Etanercept for Crohn's disease.

PMID- 14973206
TI  - Medical mystery--the answer.

PMID- 14973207
TI  - Hemofiltration and the prevention of radiocontrast-agent-induced nephropathy.

PMID- 14973208
TI  - Ozone--from environmental pollutant to atherogenic determinant.

PMID- 14973209
TI  - The new Medicare prescription-drug benefit--a pure power play.

PMID- 14973210
TI  - Defining adequate surgery for primary melanoma.

PMID- 14973211
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 6-2004. A 35-year-old woman with extensive, deep burns from a
      nightclub fire.

PMID- 14973212
TI  - Images in clinical medicine. Ocular melanocytosis.

PMID- 14973213
TI  - Acute chemical emergencies.

PMID- 14973214
TI  - Management of overactive bladder.

PMID- 14973215
TI  - Previous preterm and small-for-gestational-age births and the subsequent risk of
      stillbirth.
AB  - BACKGROUND: Some causes of stillbirth may also lead to fetuses that are small for
      gestational age (have a low birth weight with respect to their gestational age)
      or are delivered preterm (before 37 weeks of gestation). It is not known whether
      the birth of a previous small-for-gestational-age or preterm infant increases the
      subsequent risk of stillbirth. METHODS: We assessed the associations between
      previous adverse outcomes of pregnancy and the risk of stillbirth in a nationwide
      Swedish study of 410,021 women who delivered first and second consecutive
      singleton infants between 1983 and 1997. There were 1842 and 1062 stillbirths
      during the first and second pregnancies, respectively. RESULTS: As compared with
      women whose first infant was born at term (37 weeks of gestation or more) and was
      not small for gestational age, women whose first infant was born at term or
      preterm and was small for gestational age had an increased risk of stillbirth
      during their second pregnancy. The odds ratios for subsequent stillbirth, after
      adjustment for covariates known to be associated with an increased risk of
      stillbirth, were 2.1 (95 percent confidence interval, 1.6 to 2.8) among women
      with a first infant who was born at term and was small for gestational age, 3.4
      (95 percent confidence interval, 2.1 to 5.6) among women with a first infant who
      was moderately (32 to 36 weeks of gestation) preterm and small for gestational
      age, and 5.0 (95 percent confidence interval, 2.5 to 9.8) among women with a
      first infant who was very (before 32 weeks of gestation) preterm and was small
      for gestational age. The odds ratio for subsequent stillbirth among women with a
      first stillborn infant was 2.5 (95 percent confidence interval, 1.4 to 4.7), as
      compared with women whose first infant was not stillborn. The rates of stillbirth
      in second pregnancies ranged from 2.4 per 1000 births among women whose first
      infant was born at term and was not small for gestational age to 19.0 per 1000
      births among women whose first child was very preterm and was small for
      gestational age. CONCLUSIONS: Delivery of a previous small-for-gestational-age
      infant is an important predictor of the subsequent risk of stillbirth,
      particularly if the infant was delivered preterm.

PMID- 14973216
TI  - Alendronate versus calcitriol for the prevention of bone loss after cardiac
      transplantation.
AB  - BACKGROUND: Osteoporosis is a well-known complication of cardiac transplantation.
      We conducted a randomized trial comparing alendronate with calcitriol for the
      prevention of bone loss during the first year after cardiac transplantation.
      METHODS: A total of 149 patients were randomly assigned to receive either
      alendronate (10 mg per day) or calcitriol (0.5 microg per day) a mean (+/-SD) of
      21+/-11 days after transplantation. Estimates of bone loss and the incidence of
      fractures among untreated patients were obtained from a reference group of 27
      prospectively recruited patients who received cardiac transplants within the same
      period as the intervention groups. RESULTS: At one year, the bone mineral density
      at the lumbar spine had decreased by a mean of 0.7 percent in the alendronate
      group and 1.6 percent in the calcitriol group (P=0.25 for the test of no
      difference). The bone mineral density at the femoral neck decreased by a mean of
      1.7 percent in the alendronate group and 2.1 percent in the calcitriol group
      (P=0.69). In the reference group, the mean bone mineral density at the lumbar
      spine decreased by 3.2 percent (P=0.03 for the comparison with the alendronate
      group; P=0.15 for the comparison with the calcitriol group), and the mean density
      at the femoral neck decreased by 6.2 percent (P=0.001 for comparisons with both
      intervention groups). The incidence of vertebral fractures did not differ
      significantly among the groups (6.8 percent in the alendronate group, 3.6 percent
      in the calcitriol group, and 13.6 percent in the reference group). Hypercalciuria
      developed in 27 percent of the patients in the calcitriol group and 7 percent of
      those in the alendronate group (P=0.01). CONCLUSIONS: The degree of bone loss and
      the rates of fracture did not differ significantly between the intervention
      groups. Calcitriol was associated with a higher risk of hypercalciuria.
      Alendronate-treated patients sustained less bone loss at the spine than those in
      the reference group, and both intervention groups sustained less bone loss at the
      hip than the reference group. The requirement for monitoring the serum and
      urinary calcium levels in calcitriol-treated patients makes alendronate more
      attractive for the prevention of bone loss early after cardiac transplantation.

PMID- 14973217
TI  - Excision margins in high-risk malignant melanoma.
AB  - BACKGROUND: Controversy exists concerning the necessary margin of excision for
      cutaneous melanoma 2 mm or greater in thickness. METHODS: We conducted a
      randomized clinical trial comparing 1-cm and 3-cm margins. RESULTS: Of the 900
      patients who were enrolled, 453 were randomly assigned to undergo surgery with a
      1-cm margin of excision and 447 with a 3-cm margin of excision; the median follow
      up was 60 months. A 1-cm margin of excision was associated with a significantly
      increased risk of locoregional recurrence. There were 168 locoregional
      recurrences (as first events) in the group with 1-cm margins of excision, as
      compared with 142 in the group with 3-cm margins (hazard ratio, 1.26; 95 percent
      confidence interval, 1.00 to 1.59; P=0.05). There were 128 deaths attributable to
      melanoma in the group with 1-cm margins, as compared with 105 in the group with 3
      cm margins (hazard ratio, 1.24; 95 percent confidence interval, 0.96 to 1.61;
      P=0.1); overall survival was similar in the two groups (hazard ratio for death,
      1.07; 95 percent confidence interval, 0.85 to 1.36; P=0.6). CONCLUSIONS: A 1-cm
      margin of excision for melanoma with a poor prognosis (as defined by a tumor
      thickness of at least 2 mm) is associated with a significantly greater risk of
      regional recurrence than is a 3-cm margin, but with a similar overall survival
      rate.

PMID- 14973218
TI  - Small-for-gestational-age infants and risk of fetal death in subsequent
      pregnancies.

PMID- 14973219
TI  - Bone loss after cardiac transplantation.

PMID- 14973220
TI  - Dramatic improvement or death spiral--two members of congress assess the Medicare
      bill.

PMID- 14973221
TI  - Transient global amnesia and a father's worst nightmare.

PMID- 14973222
TI  - ETR-3 and CELF4 protein domains required for RNA binding and splicing activity in
      vivo.
AB  - Members of the CUG-BP and ETR-3 like factor (CELF) protein family bind within
      conserved intronic elements (called MSEs) flanking the cardiac troponin T (cTNT)
      alternative exon 5 and promote exon inclusion in vivo and in vitro. Here we use a
      comparative deletion analysis of two family members (ETR-3 and CELF4) to identify
      separate domains required for RNA binding and splicing activity in vivo. CELF
      proteins contain two adjacent RNA binding domains (RRM1 and RRM2) near the N
      terminus and one RRM (RRM3) near the C-terminus, which are separated by a 160-230
      residue divergent domain of unknown function. Either RRM1 or RRM2 of CELF4 are
      necessary and sufficient for binding MSE RNA and RRM2 plus an additional 66 amino
      acids of the divergent domain are as effective as full-length protein in
      activating MSE-dependent splicing in vivo. Non-overlapping N- and C-terminal
      regions of ETR-3 containing either RRM1 and RRM2 or RRM3 plus segments of the
      adjacent divergent domain activate MSE-dependent exon inclusion demonstrating an
      unusual functional redundancy of the N- and C-termini of the protein. These
      results identify specific regions of ETR-3 and CELF4 that are likely targets of
      protein-protein interactions required for splicing activation.

PMID- 14973223
TI  - Mer1p is a modular splicing factor whose function depends on the conserved U2
      snRNP protein Snu17p.
AB  - Mer1p activates the splicing of at least three pre-mRNAs (AMA1, MER2, MER3)
      during meiosis in the yeast Saccharomyces cerevisiae. We demonstrate that
      enhancer recognition by Mer1p is separable from Mer1p splicing activation. The C
      terminal KH-type RNA-binding domain of Mer1p recognizes introns that contain the
      Mer1p splicing enhancer, while the N-terminal domain interacts with the
      spliceosome and activates splicing. Prior studies have implicated the U1 snRNP
      and recognition of the 5' splice site as key elements in Mer1p-activated
      splicing. We provide new evidence that Mer1p may also function at later steps of
      spliceosome assembly. First, Mer1p can activate splicing of introns that have
      mutated branch point sequences. Secondly, Mer1p fails to activate splicing in the
      absence of the non-essential U2 snRNP protein Snu17p. Thirdly, Mer1p interacts
      with the branch point binding proteins Mud2p and Bbp1p and the U2 snRNP protein
      Prp11p by two-hybrid assays. We conclude that Mer1p is a modular splicing
      regulator that can activate splicing at several early steps of spliceosome
      assembly and depends on the activities of both U1 and U2 snRNP proteins to
      activate splicing.

PMID- 14973224
TI  - Overexpression of phage-type RNA polymerase RpoTp in tobacco demonstrates its
      role in chloroplast transcription by recognizing a distinct promoter type.
AB  - Plant cells possess three DNA-containing compartments, the nucleus, the
      mitochondria and the plastids. Accordingly, plastid gene regulation is fairly
      complex. Albeit plastids retained their own genome and prokaryotic-type gene
      expression system by a plastid-encoded RNA polymerase (PEP), they need a second
      nuclear-encoded plastid transcription activity, NEP. Candidate genes for putative
      NEP catalytic subunits have been cloned in Arabidopsis thaliana (AtRpoTp) and
      Nicotiana sylvestris (NsRpoTp). To provide evidence for RpoTp as a gene encoding
      a NEP catalytic subunit, we introduced the AtRpoTp and NsRpoTp cDNAs into the
      tobacco nucleus under the control of the strong constitutive CaMV 35S promoter.
      Analysis of transcription from NEP and PEP promoters in these transgenic plants
      using primer extension assays revealed enhanced transcription from typical type I
      NEP promoters as PatpB-289 in comparison with the wild type. These data provide
      direct evidence that RpoTp is a catalytic subunit of NEP and involved in
      recognition of a distinct subset of type I NEP promoters.

PMID- 14973225
TI  - Identification of NH...N hydrogen bonds by magic angle spinning solid state NMR
      in a double-stranded RNA associated with myotonic dystrophy.
AB  - RNA plays a central role in biological processes and exhibits a variety of
      secondary and tertiary structural features that are often stabilized via hydrogen
      bonds. The distance between the donor and acceptor nitrogen nuclei involved in
      NH...N hydrogen bonds in nucleic acid base pairs is typically in the range of 2.6
      2.9 A. Here, we show for the first time that such spatial proximity between 15N
      nitrogen nuclei can be conveniently monitored via magic angle spinning solid
      state NMR on a uniformly 15N-labelled RNA. The presence of NH.N hydrogen bonds is
      reflected as cross-peaks between the donor and acceptor nitrogen nuclei in 2D 15N
      dipolar chemical shift correlation spectra. The RNA selected for this
      experimental study was a CUG repeat expansion implicated in the neuromuscular
      disease myotonic dystrophy. The results presented provide direct evidence that
      the CUG repeat expansion adopts a double-stranded conformation.

PMID- 14973226
TI  - Neuroprotective role of a proline-rich Akt substrate in apoptotic neuronal cell
      death after stroke: relationships with nerve growth factor.
AB  - The Akt signaling pathway contributes to regulation of apoptosis after a variety
      of cell death stimuli. A novel proline-rich Akt substrate (PRAS) was recently
      detected and found to be involved in apoptosis. In our study, Akt activation was
      modulated by growth factors, and treatment with nerve growth factor (NGF) reduced
      apoptotic cell death after ischemic injury. However, the role of the PRAS pathway
      in apoptotic neuronal cell death after ischemia remains unknown. Phosphorylated
      PRAS (pPRAS) and the binding of pPRAS/phosphorylated Akt (pPRAS/pAkt) to 14-3-3
      (pPRAS/14-3-3) were detected, and their expression transiently decreased in mouse
      brains after transient focal cerebral ischemia (tFCI). Liposome-mediated pPRAS
      cDNA transfection induced overexpression of pPRAS, promoted pPRAS/14-3-3, and
      inhibited apoptotic neuronal cell death after tFCI. The expression of pPRAS,
      pPRAS/pAkt, and pPRAS/14-3-3 increased in NGF-treated mice but decreased with
      inhibition of phosphatidylinositol-3 kinase and the NGF receptor after tFCI.
      These results suggest that PRAS phosphorylation and its interaction with pAkt and
      14-3-3 might play an important role in neuroprotection mediated by NGF in
      apoptotic neuronal cell death after tFCI.

PMID- 14973227
TI  - GABA release from proopiomelanocortin neurons.
AB  - Neural networks controlling food intake and energy homeostasis clearly involve
      proopiomelanocortin (POMC) neurons and their peptide transmitters. alpha
      melanocyte-stimulating hormone from arcuate POMC neurons potently reduces food
      intake, whereas arcuate neuropeptide Y (NPY) neurons act in opposition to
      stimulate food intake. In addition to orexigenic peptides, NPY neurons also
      release the inhibitory neurotransmitter GABA, which can act in a local circuit to
      inhibit POMC neuron activity. Whether or not reciprocal inhibition could occur
      has not yet been determined, because the presence of a rapid neurotransmitter in
      POMC neurons has not been demonstrated previously. Here, we used primary cultures
      of fluorescently labeled POMC neurons that had formed recurrent synapses
      (autapses) to detect the release of neurotransmitter. When an action potential
      was evoked in the axon of a POMC neuron with autapses, a short-latency synaptic
      current was recorded in the same cell. The autaptic current was abolished by
      GABA(A) receptor antagonists and substantially inhibited by opioids. Double-label
      in situ RNA hybridization for POMC and glutamic acid decarboxylase, the GABA
      synthetic enzyme, revealed colocalization of mRNAs in approximately one-third of
      POMC neurons in vivo. Our results suggest that these neurons can exert rapid
      inhibitory effects via the release of GABA, in addition to the more sustained
      actions provided by POMC peptides. However, this rapid inhibition may not play a
      major role within local hypothalamic circuits, but rather is likely to be
      important in more distant projection areas as indicated by the colocalization of
      vesicular GABA transporter immunoreactivity predominantly in extrahypothalamic
      POMC terminals.

PMID- 14973228
TI  - Conditional ablation of the neural cell adhesion molecule reduces precision of
      spatial learning, long-term potentiation, and depression in the CA1 subfield of
      mouse hippocampus.
AB  - NCAM, a neural cell adhesion molecule of the immunoglobulin superfamily, is
      involved in neuronal migration and differentiation, axon outgrowth and
      fasciculation, and synaptic plasticity. To dissociate the functional roles of
      NCAM in the adult brain from developmental abnormalities, we generated a mutant
      in which the NCAM gene is inactivated by cre-recombinase under the control of the
      calcium-calmodulin-dependent kinase II promoter, resulting in reduction of NCAM
      expression predominantly in the hippocampus. This mutant (NCAMff+) did not show
      the overt morphological and behavioral abnormalities previously observed in
      constitutive NCAM-deficient (NCAM-/-) mice. However, similar to the NCAM-/-
      mouse, a reduction in long-term potentiation (LTP) in the CA1 region of the
      hippocampus was revealed. Long-term depression was also abolished in NCAMff+
      mice. The deficit in LTP could be rescued by elevation of extracellular Ca2+
      concentrations from 1.5 or 2.0 to 2.5 mm, suggesting an involvement of NCAM in
      regulation of Ca2+-dependent signaling during LTP. Contrary to the NCAM-/- mouse,
      LTP in the CA3 region was normal, consistent with normal mossy fiber lamination
      in NCAMff+ as opposed to abnormal lamination in NCAM-/- mice. NCAMff+ mutants did
      not show general deficits in short- and long-term memory in global landmark
      navigation in the water maze but were delayed in the acquisition of precise
      spatial orientation, a deficit that could be overcome by training. Thus, mice
      conditionally deficient in hippocampal NCAM expression in the adult share certain
      abnormalities characteristic of NCAM-/- mice, highlighting the role of NCAM in
      the regulation of synaptic plasticity in the CA1 region.

PMID- 14973229
TI  - Decreased phosphorylation of NMDA receptor type 1 at serine 897 in brains of
      patients with Schizophrenia.
AB  - NMDA receptor hypofunction in schizophrenia has been inferred by a large number
      of clinical and preclinical observations; however, whether and how NMDA receptors
      are exactly involved in the pathogenesis of schizophrenia are still unknown and
      subject to interpretation. Here we show, in two independent samples of brains
      from patients with schizophrenia, a significant decrease in the phosphorylation
      level at serine 897 (S897) of the NMDA receptor type 1 (NR1) subunit. Our
      finding, together with a previous report that antipsychotics increase
      phosphorylation of NR1 at S897 in vivo, strongly suggests that insufficient
      phosphorylation at S897 may contribute to the neuronal pathology underlying
      schizophrenia.

PMID- 14973230
TI  - Limbic and motor circuitry underlying footshock-induced reinstatement of cocaine
      seeking behavior.
AB  - The role of limbic, cortical, and striatal circuitry in a footshock reinstatement
      model of relapse to cocaine seeking was evaluated. Transient inhibition of the
      central extended amygdala [CEA; including the central nucleus of the amygdala
      (CN), ventral bed nucleus of the stria terminalis (BNSTv), and nucleus accumbens
      shell (NAshell)], ventral tegmental area (VTA), and motor circuitry [including
      the dorsal prefrontal cortex (PFCd), nucleus accumbens core (NAcore), and ventral
      pallidum (VP)] blocked the ability of footshock stress to reinstate lever
      pressing previously associated with cocaine delivery. However, inhibition of the
      basolateral amygdala, mediodorsal nucleus of the thalamus, or the ventral
      prefrontal cortex had no effect on drug-seeking behavior. These data suggest that
      footshock stress activates limbic circuitry of the CEA that, via the VTA,
      activates motor output circuitry responsible for producing lever press
      responding. Consistent with this notion, the D1/D2 dopamine receptor antagonist
      fluphenazine blocked footshock-induced reinstatement when infused into the PFCd.
      Further, inhibition of the NAshell blocked a footshock-induced increase in
      dopamine within the PFC and concomitantly blocked reinstatement responding. Also
      supporting the idea of a CEA-VTA-motor circuit in stress-induced reinstatement of
      cocaine seeking, inactivation of the PFCd was shown to block stress-induced
      glutamate release within the NAcore while concurrently inhibiting reinstatement
      responding. Taken together, these data suggest that footshock activates limbic
      circuitry in the CEA, which in turn activates a VTA dopamine projection to the
      PFCd. The rise in dopamine within the PFCd initiates reinstatement via a
      glutamatergic projection to the NAcore.

PMID- 14973231
TI  - Mechanisms of dendritic elaboration of sensory neurons in Drosophila: insights
      from in vivo time lapse.
AB  - In vivo time-lapse multiphoton microscopy was used to analyze the remodeling of
      the dendritic arborizing (da) sensory neuron known as dorsal dendritic arborizing
      neuron E (ddaE) during metamorphosis. After its larval processes have been
      removed, the cell body of ddaE repositions itself on the body wall between 25 and
      40 hr after puparium formation (APF) and begins its adult outgrowth at 40 hr APF.
      The scaffold of the arbor is laid down between 40 and 54 hr APF, when growth is
      characterized by high filopodial activity at both terminal and interstitial
      positions and by branch retraction along with branch establishment. Later in
      development, filopodial activity remains high but is confined to terminal
      branches, and branch retraction is no longer seen. Treatment with the insect
      hormone juvenile hormone (JH), a key regulator of metamorphosis, alters the shape
      and complexity of the adult dendritic tree in a time-dependent manner. Early
      treatments with juvenile hormone mimic (JHm) appear to repress extension programs
      and maintain retraction programs. With later JHm treatments, extension programs
      appear normal, but retraction programs are maintained beyond their normal time.
      The JH treatments show the importance of retraction programs in establishing the
      overall arbor shape.

PMID- 14973232
TI  - Glutathione peroxidase-catalase cooperativity is required for resistance to
      hydrogen peroxide by mature rat oligodendrocytes.
AB  - Oxidative mechanisms of injury are important in many neurological disorders,
      including hypoxic-ischemic brain damage. Cerebral palsy after preterm birth is
      hypothesized to be caused by hypoxic-ischemic injury of developing
      oligodendrocytes (OLs). Here we examined the developmental sensitivity of OLs to
      exogenous hydrogen peroxide (H2O2) with stage-specific rat oligodendrocyte
      cultures. We found that H2O2 itself or that generated by glucose oxidase was more
      toxic to developing than to mature OLs. Mature OLs were able to degrade H2O2
      faster than developing OLs, suggesting that higher antioxidant enzyme activity
      might be the basis for their resistance. Catalase expression and activity were
      relatively constant during oligodendrocyte maturation, whereas glutathione
      peroxidase (GPx) was upregulated with a twofold to threefold increase in its
      expression and activity. Thus, it appeared that the developmental change in
      resistance to H2O2 was caused by modulation of GPx but not by catalase
      expression. To test the relative roles of catalase and GPx in the setting of
      oxidative stress, we measured enzyme activity in cells exposed to H2O2 and found
      that H2O2 induced a decrease in catalase activity in developing but not in mature
      OLs. Inhibition of GPx by mercaptosuccinate led to an increase in the
      vulnerability of mature OLs to H2O2 as well as a reduction in catalase activity.
      Finally, H2O2-dependent inactivation of catalase in developing OLs was prevented
      by the GPx mimic ebselen. These data provide evidence for a key role for GPx
      catalase cooperativity in the resistance of mature OLs to H2O2-induced cell
      death.

PMID- 14973233
TI  - The CACNA1F gene encodes an L-type calcium channel with unique biophysical
      properties and tissue distribution.
AB  - Glutamate release from rod photoreceptors is dependent on a sustained calcium
      influx through L-type calcium channels. Missense mutations in the CACNA1F gene in
      patients with incomplete X-linked congenital stationary night blindness implicate
      the Ca(v)1.4 calcium channel subtype. Here, we describe the functional and
      pharmacological properties of transiently expressed human Ca(v)1.4 calcium
      channels. Ca(v)1.4 is shown to encode a dihydropyridine-sensitive calcium channel
      with unusually slow inactivation kinetics that are not affected by either calcium
      ions or by coexpression of ancillary calcium channel beta subunits. Additionally,
      the channel supports a large window current and activates near -40 mV in 2 mM
      external calcium, making Ca(v)1.4 ideally suited for tonic calcium influx at
      typical photoreceptor resting potentials. Introduction of base pair changes
      associated with four incomplete X-linked congenital night blindness mutations
      showed that only the G369D alteration affected channel activation properties.
      Immunohistochemical analyses show that, in contrast with previous reports,
      Ca(v)1.4 is widely distributed outside the retina, including in the immune
      system, thus suggesting a broader role in human physiology.

PMID- 14973234
TI  - Heat shock protein 70 participates in the neuroprotective response to
      intracellularly expressed beta-amyloid in neurons.
AB  - Intracellular beta-amyloid 42 (Abeta42) accumulation is increasingly recognized
      as an early event in the pathogenesis of Alzheimer's disease (AD). We have
      developed a doxycycline-inducible adenoviral-based system that directs
      intracellular Abeta42 expression and accumulation into the endoplasmic reticulum
      of primary neuronal cultures in a regulated manner. Abeta42 exhibited a
      perinuclear distribution in cell bodies and an association with vesicular
      compartments. Virally expressed intracellular Abeta42 was toxic to neuronal
      cultures 24 hr after induction in a dose-dependent manner. Abeta42 expression
      prompted the rapid induction of stress-inducible Hsp70 protein in neurons, and
      virally mediated Hsp70 overexpression rescued neurons from the toxic effects of
      intracellular Abeta accumulation. Together, these results implicate the cellular
      stress response as a possible modulator of Abeta-induced toxicity in neuronal
      cultures.

PMID- 14973235
TI  - Single spine Ca2+ signals evoked by coincident EPSPs and backpropagating action
      potentials in spiny stellate cells of layer 4 in the juvenile rat somatosensory
      barrel cortex.
AB  - The precise timing of presynaptic and postsynaptic activity results in synaptic
      modifications, which depend on calcium influx. [Ca2+] transients in the spines of
      spiny neurons in layer 4 (L4) of the somatosensory barrel cortex of young rats
      were investigated in thalamocortical brain slices by two-photon excitation
      microscopy to determine the spike timing dependence of the Ca2+ signal during
      near-coincident presynaptic and postsynaptic activity. [Ca2+] transients evoked
      by backpropagating action potentials (bAPs) were mediated by voltage-dependent
      Ca2+ channels and were of comparable size in a spine and adjacent dendritic
      shaft. They decreased with the distance of the spine from the soma. EPSP-evoked
      [Ca2+] transients were restricted to spine heads and were mediated almost
      entirely by Ca2+ influx through NMDA receptors (NMDARs). Their amplitude was
      independent of the position of the spine along the dendritic arbor. bAPs
      interacted with EPSPs to generate sublinear or supralinear Ca2+ signals in a
      spine when EPSP and bAP occurred within a time window of 50 msec. Synaptic
      stimulation, coincident with a bAP, evoked a large postsynaptic Ca2+ influx that
      was restricted to a single spine, even after EPSPs were blocked by the AMPA
      receptor antagonist NBQX that rendered synapses effectively "electrically
      silent." We conclude that the spines of L4 cells can act as sharply tuned
      detectors for patterns of APs occurring in the boutons of the afferents to L4
      cells and the spines of L4 cell dendrites. The readout for near-coincident
      presynaptic and postsynaptic APs is a large transient Ca2+ influx into
      synaptically active spines mediated by the brief unblocking of NMDARs during the
      dendritic bAP.

PMID- 14973236
TI  - Minimum essential factors required for vesicle mobilization at hippocampal
      synapses.
AB  - Studies on the mechanisms that underlie the function of small central presynaptic
      terminals have been hampered by the inaccessibility of these synapses to soluble
      reagents. Here, we permeabilized hippocampal synapses in culture, manipulated
      their interior, and monitored the resulting changes in vesicle mobilization with
      the styryl dye FM2-10. Using this method, we found that 1 microm Ca2+ after
      incubation with GTP or GTP-gamma-S could mobilize approximately 90% of the total
      recycling pool, whereas 1 microm Ca2+ application after dialysis of permeabilized
      synapses with GDP-beta-S mobilized approximately 30% of the recycling vesicles,
      presumably corresponding to the readily releasable pool. In electron micrographs
      of permeabilized hippocampal synapses stimulated with 1 microm Ca2+, we could
      detect significant vesicle depletion after preincubation with GTP-gamma-S,
      whereas preincubation with GDP-beta-S left the total vesicle pool relatively
      intact. Taken together, in this system replenishment of the readily releasable
      pool by the reserve vesicles was strictly GTP dependent. In contrast, vesicle
      replenishment and release did not require ATP or N-ethylmaleimide-sensitive
      factor (NSF); however, this process involved formation of new soluble NSF
      attachment protein receptor (SNARE) complexes as judged by its sensitivity to
      tetanus toxin. These results suggest that in hippocampal synapses, vesicle
      mobilization and replenishment of the readily releasable pool require GTP and
      Ca2+ but do not necessitate ATP-dependent priming and SNARE recycling.

PMID- 14973237
TI  - Disruption of endocannabinoid release and striatal long-term depression by
      postsynaptic blockade of endocannabinoid membrane transport.
AB  - Activation of the CB1 cannabinoid receptor inhibits neurotransmission at numerous
      synapses in the brain. Indeed, CB1 is essential for certain types of both short-
      and long-term synaptic depression. It was demonstrated recently that CB1 is
      critical for activity-dependent long-term depression (LTD) at glutamatergic
      corticostriatal synapses in acute brain slice preparations. Here, we show that
      CB1 activation is necessary, but not solely sufficient, for induction of LTD and
      that the requisite signaling by endocannabinoids (eCBs) occurs during a time
      window limited to the first few minutes after high-frequency stimulation
      delivery. In addition, we have applied intracellularly anandamide membrane
      transporter inhibitors to provide novel evidence that postsynaptic transport
      mechanisms are responsible for the release of eCBs from striatal medium spiny
      neurons. These findings shed new light on the mechanisms by which transient eCB
      formation participates in the induction of long-lasting changes in synaptic
      efficacy that could contribute to brain information storage.

PMID- 14973238
TI  - Learning modifies subsequent induction of long-term potentiation-like and long
      term depression-like plasticity in human motor cortex.
AB  - Learning may alter rapidly the output organization of adult motor cortex. It is a
      long-held hypothesis that modification of synaptic strength along cortical
      horizontal connections through long-term potentiation (LTP) and long-term
      depression (LTD) forms one important mechanism for learning-induced cortical
      plasticity. Strong evidence in favor of this hypothesis was provided for rat
      primary motor cortex (M1) by showing that motor learning reduced subsequent LTP
      but increased LTD. Whether a similar relationship exists in humans is unknown.
      Here, we induced LTP-like and LTD-like plasticity in the intact human M1 by an
      established paired associative stimulation (PAS) protocol. PAS consisted of 200
      pairs of electrical stimulation of the right median nerve, followed by focal
      transcranial magnetic stimulation of the hand area of the left M1 at an interval
      equaling the individual N20 latency of the median nerve somatosensory-evoked
      cortical potential (PAS(N20)) or N20-5 msec (PAS(N20-5)). PAS(N20) induced
      reproducibly a LTP-like long-lasting (>30 min) increase in motor-evoked
      potentials from the left M1 to a thumb abductor muscle of the right hand, whereas
      PAS(N20-5) induced a LTD-like decrease. Repeated fastest possible thumb abduction
      movements resulted in learning, defined by an increase in maximum peak
      acceleration of the practiced movements, and prevented subsequent PAS(N20)
      induced LTP-like plasticity but enhanced subsequent PAS(N20-5)-induced LTD-like
      plasticity. The same number of repeated slow thumb abduction movements did not
      result in learning and had no effects on PAS-induced plasticity. Findings support
      the view that learning in human M1 occurs through LTP-like mechanisms.

PMID- 14973239
TI  - A neural correlate of reward-based behavioral learning in caudate nucleus: a
      functional magnetic resonance imaging study of a stochastic decision task.
AB  - Humans can acquire appropriate behaviors that maximize rewards on a trial-and
      error basis. Recent electrophysiological and imaging studies have demonstrated
      that neural activity in the midbrain and ventral striatum encodes the error of
      reward prediction. However, it is yet to be examined whether the striatum is the
      main locus of reward-based behavioral learning. To address this, we conducted
      functional magnetic resonance imaging (fMRI) of a stochastic decision task
      involving monetary rewards, in which subjects had to learn behaviors involving
      different task difficulties that were controlled by probability. We performed a
      correlation analysis of fMRI data by using the explanatory variables derived from
      subject behaviors. We found that activity in the caudate nucleus was correlated
      with short-term reward and, furthermore, paralleled the magnitude of a subject's
      behavioral change during learning. In addition, we confirmed that this
      parallelism between learning and activity in the caudate nucleus is robustly
      maintained even when we vary task difficulty by controlling the probability.
      These findings suggest that the caudate nucleus is one of the main loci for
      reward-based behavioral learning.

PMID- 14973240
TI  - Early serotonergic projections to Cajal-Retzius cells: relevance for cortical
      development.
AB  - Although the serotonergic system plays an important role in various neurological
      disorders, the role of early serotonergic projections to the developing cerebral
      cortex is not well understood. Because serotonergic fibers enter the marginal
      zone (MZ) before birth, it has been suggested that they may influence cortical
      development through synaptic contacts with Cajal-Retzius (CR) cells. We used
      immunohistochemistry combined with confocal and electron microscopy to show that
      the earliest serotonergic projections to the MZ form synaptic contacts with the
      somata and proximal dendrites of CR cells as early as embryonic day 17. To
      elucidate the functional significance of these early serotonergic contacts with
      CR cells, we perturbed their normal development by injecting pregnant mice with 5
      methoxytryptamine. Lower reelin levels were detected in the brains of newborn
      pups from the exposed animals. Because reelin plays an important role in the
      cortical laminar and columnar organization during development, we killed some
      pups from the same litters on postnatal day 7 and analyzed their presubicular
      cortex. We found that the supragranular layers of the presubicular cortex (which
      normally display a visible columnar deployment of neurons) were altered in the
      treated animals. Our results suggest a mechanism of how serotonergic
      abnormalities during cortical development may disturb the normal cortical
      organization; and, therefore, may be relevant for understanding neurological
      disorders in which abnormalities of the serotonergic system are accompanied by
      cortical pathology (such as autism).

PMID- 14973241
TI  - Counteracting the Nogo receptor enhances optic nerve regeneration if retinal
      ganglion cells are in an active growth state.
AB  - Mature retinal ganglion cells (RGCs), like other CNS neurons, cannot regrow
      injured axons into a myelin-rich environment. If stimulated by macrophage-derived
      factors, however, RGCs can regenerate their axons for considerable distances
      through the distal optic nerve. Using this "sensitized background," we
      investigated the effects of either increasing the expression or suppressing the
      activity of the Nogo receptor (NgR). NgR mediates the growth-inhibiting effects
      of three myelin proteins, Nogo, OMgp (oligodendrocyte-myelin glycoprotein), and
      MAG (myelin-associated glycoprotein). Transfecting growth-sensitized RGCs with
      adeno-associated viruses expressing a dominant-negative form of NgR (NgR(DN))
      increased axon regeneration several-fold; however, when the growth program of
      RGCs was not activated, NgR(DN) expression had no beneficial effects.
      Overexpression of wild-type NgR blocked almost all regeneration from growth
      sensitized RGCs and caused axons proximal to the lesion site to retract. We
      conclude that gene therapy is an effective approach to enhancing axon
      regeneration in the CNS and that inactivation of NgR functioning greatly enhances
      axon regeneration provided the intrinsic growth program of neurons is activated.

PMID- 14973242
TI  - Specific Inhibition of IkappaB kinase reduces hyperalgesia in inflammatory and
      neuropathic pain models in rats.
AB  - Phosphorylation of IkappaB through IkappaB kinase (IKK) is the first step in
      nuclear factor kappaB (NF-kappaB) activation and upregulation of NF-kappaB
      responsive genes. Hence, inhibition of IKK activity may be expected to prevent
      injury-, infection-, or stress-induced upregulation of various proinflammatory
      genes and may thereby reduce hyperalgesia and inflammation. In the present study,
      we tested this hypothesis using a specific and potent IKK inhibitor (S1627). In
      an IKK assay, S1627 inhibited IKK activity with an IC50 value of 10.0 +/- 1.2 nm.
      In cell culture experiments, S1627 inhibited interleukin (IL)-1beta-stimulated
      nuclear translocation and DNA-binding of NF-kappaB. Plasma concentration time
      courses after intraperitoneal injection revealed a short half-life of 2.8 hr in
      rats. Repeated intraperitoneal injections were, therefore, chosen as the dosing
      regimen. S1627 reversed thermal and mechanical hyperalgesia at 3x 30 mg/kg in the
      zymosan-induced paw inflammation model and reduced the inflammatory paw edema at
      3x 40 mg/kg. S1627 also significantly reduced tactile and cold allodynia in the
      chronic constriction injury model of neuropathic pain at 30 mg/kg once daily. The
      drug had no effect on acute inflammatory nociception in the formalin test and did
      not affect responses to heat and tactile stimuli in naive animals. As
      hypothesized, S1627 prevented the zymosan-induced nuclear translocation of NF
      kappaB in the spinal cord and the upregulation of NF-kappaB-responsive genes
      including cyclooxygenase-2, tumor necrosis factor-alpha, and IL-1beta. Our data
      indicate that IKK may prove an interesting novel drug target in the treatment of
      pathological pain and inflammation.

PMID- 14973243
TI  - Effects of training on neuronal activity and interactions in primary and higher
      visual cortices in the alert cat.
AB  - The effects of behavioral training on early visual representations have been
      elusive when assessed with firing rates. Learning-induced changes in performance,
      however, suggest that representations should encompass early cortical stages.
      Here, we address the question of whether training-induced effects are pertinent
      to neuronal activity outside the task proper, which is a requirement if
      subsequent perceptional processes should profit from training. To search for a
      neuronal signature of training effects beyond firing rates, we measured local
      field potentials, multiunit and isolated spike activity during passive viewing of
      previously learned stimulus response associations (S+ and S-) in areas 17/18 and
      21a of two alert cats. Evoked potential responses as well as gamma oscillations
      even during the first 200 msec were found to be stronger for S+ in both areas.
      Most importantly, the later parts of the response (>200 msec) not only exhibit a
      highly significant difference in coherent gamma oscillations for S+ and S- both
      within and across areas, but are also characterized by a pronounced preference in
      firing rate for S+ in area 21a, whereas primary cortex shows a nonsignificant
      trend for weaker spike responses. From these results, we conclude that training
      induced plasticity occurs in adult visual cortex for behaviorally relevant
      stimuli by changing primarily the temporal structure of neuronal activity at
      early stages of cortical processing, whereas later stages of cortical processing
      express the increased coherence of their input in elevated firing rates.

PMID- 14973244
TI  - The effect of perceptual learning on neuronal responses in monkey visual area V4.
AB  - Previous studies have shown that perceptual learning can substantially alter the
      response properties of neurons in the primary somatosensory and auditory
      cortices. Although psychophysical studies suggest that perceptual learning
      induces similar changes in primary visual cortex (V1), studies that have measured
      the response properties of individual neurons have failed to find effects of the
      size described for the other sensory systems. We have examined the effect of
      learning on neuronal response properties in a visual area that lies at a later
      stage of cortical processing, area V4. Adult macaque monkeys were trained
      extensively on orientation discrimination at a specific retinal location using a
      narrow range of orientations. During the course of training, the subjects
      achieved substantial improvement in orientation discrimination that was primarily
      restricted to the trained location. After training, neurons in V4 with receptive
      fields overlapping the trained location had stronger responses and narrower
      orientation tuning curves than neurons with receptive fields in the opposite,
      untrained hemifield. The changes were most prominent for neurons that preferred
      orientations close to the trained range of orientations. These results provide
      the first demonstration of perceptual learning modifying basic neuronal response
      properties at an intermediate level of visual cortex and give insights into the
      distribution of plasticity across adult visual cortex.

PMID- 14973245
TI  - Material-specific recognition memory deficits elicited by unilateral hippocampal
      electrical stimulation.
AB  - Although the medial temporal lobe is thought to be critical for recognition
      memory (RM), the specific role of the hippocampus in RM remains uncertain. We
      investigated the effects of transient unilateral hippocampal electrical
      stimulation (ES), subthreshold for afterdischarge, on delayed item RM in epilepsy
      patients implanted with bilateral hippocampal depth electrodes. RM was assessed
      using a novel computer-controlled test paradigm in which ES to left or right
      hippocampus was either absent (baseline) or synchronized with item presentation.
      Subsequent yes-no RM performance revealed a double dissociation between material
      specific RM and the lateralization of ES. Left hippocampal ES produced word RM
      deficits, whereas right hippocampal ES produced face RM deficits. Our findings
      provide the first demonstration in humans that selective unilateral stimulation
      induced hippocampal disruption is sufficient to produce impairments on delayed RM
      tasks and provide support for the material-specific laterality of hippocampal
      function with respect to RM.

PMID- 14973246
TI  - A single infusion of brain-derived neurotrophic factor into the ventral tegmental
      area induces long-lasting potentiation of cocaine seeking after withdrawal.
AB  - Cocaine addiction in humans is associated with long-term propensity to relapse.
      Using a rat relapse model, we found that cocaine seeking induced by exposure to
      cocaine-associated cues progressively increases after withdrawal. This
      progressive increase is associated with increases in brain-derived nerve growth
      factor (BDNF) levels within the mesolimbic dopamine system. Based on these
      findings, we studied whether BDNF infusions into the ventral tegmental area
      (VTA), the cell body region of mesolimbic dopamine neurons, would potentiate
      cocaine seeking after withdrawal. Rats were trained to self-administer cocaine
      for 10 d, and cocaine seeking was measured in extinction tests 3, 10, or 30 d
      after withdrawal. During testing, rats were exposed to contextual cues that had
      predicted cocaine availability during training, and lever presses resulted in
      contingent presentations of a discrete tone-light cue that was previously
      temporally paired with cocaine infusions. BDNF (0-0.75 microg/site) or nerve
      growth factor (NGF; 0-0.75 microg/site) was infused into the VTA 1-2 hr after the
      last self-administration session. To examine the role of the mitogen-activated
      protein kinase (MAPK) pathway in BDNF effects, U0126 (1 microg/site), an MEK
      inhibitor, was used. A single intra-VTA infusion of BDNF, but not NGF, induced
      long-lasting enhancement of cocaine seeking for up to 30 d, an effect reversed by
      U0126. In contrast, neither BDNF infusions into the substantia nigra, nor acute
      intra-VTA BDNF infusions 2 hr before testing on day 3 of withdrawal, were
      effective. These data suggest that BDNF-mediated neuroadaptations in mesolimbic
      areas are involved in the persistent cocaine seeking induced by exposure to drug
      cues after withdrawal.

PMID- 14973247
TI  - Acute and chronic ethanol alter glutamatergic transmission in rat central
      amygdala: an in vitro and in vivo analysis.
AB  - The modulation of glutamatergic transmission by ethanol may contribute to ethanol
      intoxication, reinforcement, tolerance, and dependence. Therefore, we used in
      vitro electrophysiological and in vivo microdialysis techniques to investigate
      the effects of acute and chronic ethanol on glutamatergic transmission in the
      central nucleus of amygdala (CeA). Superfusion of 5-66 mM ethanol decreased
      compound glutamatergic EPSPs and EPSCs in CeA neurons, with half-maximal
      inhibition elicited by 14 mM ethanol. Ethanol (44 mM) decreased both non-NMDAR-
      and NMDAR-mediated EPSPs and EPSCs by 21%. Both the ethanol- and ifenprodil
      induced depression of NMDAR-mediated EPSPs and EPSCs was enhanced in rats that
      received chronic ethanol treatment (CET). Ifenprodil also occluded the ethanol
      effect, suggesting that NR2B subunit-containing receptors may be involved. With
      local applications of NMDA, acute ethanol elicited a greater inhibition of NMDA
      currents in slices taken from CET (47%) compared with naive (30%) animals,
      suggesting that CET sensitizes NMDA receptors to ethanol. Acute ethanol also
      reduced paired pulse facilitation of EPSPs and EPSCs only in CET animals,
      suggesting acute ethanol-induced increase of glutamate release. This finding was
      supported by in vivo experiments showing that infusion of ethanol (0.1-1 M) via
      reverse microdialysis significantly increased glutamate release into the CeA
      dialysate but only after CET. Moreover, baseline CeA glutamate content was
      significantly higher in CET compared with naive animals. These combined findings
      suggest that CET and withdrawal lead to neuroadaptations of glutamatergic
      transmission at both presynaptic and postsynaptic sites in CeA, and glutamatergic
      synapses in CeA may play an important role in ethanol dependence.

PMID- 14973248
TI  - Relevance of UP elements for three strong Bacillus subtilis phage phi29
      promoters.
AB  - Various Escherichia coli promoters contain, in addition to the classical -35 and 
      10 hexamers, a third recognition element, named the UP element. Located upstream
      of the -35 box, UP elements stimulate promoter activity by forming a docking site
      for the C-terminal domain of the RNA polymerase alpha subunit (alphaCTD).
      Accumulating genetic, biochemical and structural information has provided a
      detailed picture on the molecular mechanism underlying UP element-dependent
      promoter stimulation in E.coli. However, far less is known about functional UP
      elements of Bacillus subtilis promoters. Here we analyse the strong early
      sigma(A)-RNA polymerase-dependent promoters C2, A2c and A2b of the lytic
      B.subtilis phage phi29. We demonstrate that the phage promoters contain
      functional UP elements although their contribution to promoter strength is very
      different. Moreover, we show that the UP element of the A2b promoter, being
      critical for its activity, is located further upstream of the -35 box than most
      E.coli UP elements. The importance of the UP elements for the phage promoters and
      how they relate to other UP elements are discussed.

PMID- 14973249
TI  - A murine model for neuropsychiatric disorders associated with group A beta
      hemolytic streptococcal infection.
AB  - A syndrome of motoric and neuropsychiatric symptoms comprising various elements,
      including chorea, hyperactivity, tics, emotional lability, and obsessive
      compulsive symptoms, can occur in association with group A beta-hemolytic
      streptococcal (GABHS) infection. We tested the hypothesis that an immune response
      to GABHS can result in behavioral abnormalities. Female SJL/J mice were immunized
      and boosted with a GABHS homogenate in Freund's adjuvant, whereas controls
      received Freund's adjuvant alone. When sera from GABHS-immunized mice were tested
      for immunoreactivity to mouse brain, a subset was found to be immunoreactive to
      several brain regions, including deep cerebellar nuclei (DCN), globus pallidus,
      and thalamus. GABHS-immunized mice having serum immunoreactivity to DCN also had
      increased IgG deposits in DCN and exhibited increased rearing behavior in open
      field and hole-board tests compared with controls and with GABHS-immunized mice
      lacking serum anti-DCN antibodies. Rearing and ambulatory behavior were
      correlated with IgG deposits in the DCN and with serum immunoreactivity to GABHS
      proteins in Western blot. In addition, serum from a GABHS mouse reacted with
      normal mouse cerebellum in nondenaturing Western blots and immunoprecipitated C4
      complement protein and alpha-2-macroglobulin. These results are consistent with
      the hypothesis that immune response to GABHS can result in motoric and behavioral
      disturbances and suggest that anti-GABHS antibodies cross-reactive with brain
      components may play a role in their pathophysiology.

PMID- 14973250
TI  - Identification and characterization of choline transporter-like protein 2, an
      inner ear glycoprotein of 68 and 72 kDa that is the target of antibody-induced
      hearing loss.
AB  - The Kresge Hearing Research Institute-3 (KHRI-3) antibody binds to a guinea pig
      inner ear supporting cell antigen (IESCA) and causes hearing loss. To gain
      insight into the mechanism of antibody-induced hearing loss, we used antibody
      immunoaffinity purification to isolate the IESCA, which was then sequenced by
      mass spectroscopy, revealing 10 guinea pig peptides identical to sequences in
      human choline transporter-like protein 2 (CTL2). Full-length CTL2 cDNA sequenced
      from guinea pig inner ear has 85.9% identity with the human cDNA. Consistent with
      its expression on the surface of supporting cells in the inner ear, CTL2 contains
      10 predicted membrane-spanning regions with multiple N-glycosylation sites. The
      68 and 72 kDa molecular forms of inner ear CTL2 are distinguished by sialic acid
      modification of the carbohydrate. The KHRI-3 antibody binds to an N-linked
      carbohydrate on CTL2 and presumably damages the organ of Corti by blocking the
      transporter function of this molecule. CTL2 mRNA and protein are abundantly
      expressed in human inner ear. Sera from patients with autoimmune hearing loss
      bind to guinea pig inner ear with the same pattern as CTL2 antibodies. Thus, CTL2
      is a possible target of autoimmune hearing loss in humans.

PMID- 14973251
TI  - Tumor necrosis factor death receptor signaling cascade is required for amyloid
      beta protein-induced neuron death.
AB  - Tumor necrosis factor type I receptor (TNFRI), a death receptor, mediates
      apoptosis and plays a crucial role in the interaction between the nervous and
      immune systems. A direct link between death receptor activation and signal
      cascade-mediated neuron death in brains with neurodegenerative disorders remains
      inconclusive. Here, we show that amyloid-beta protein (Abeta), a major component
      of plaques in the Alzheimer's diseased brain, induces neuronal apoptosis through
      TNFRI by using primary neurons overexpressing TNFRI by viral infection or neurons
      from TNFRI knock-out mice. This was mediated via alteration of apoptotic protease
      activating factor (Apaf-1) expression that in turn induced activation of nuclear
      factor kappaB (NF-kappaB). Abeta-induced neuronal apoptosis was reduced with
      lower Apaf-1 expression, and little NF-kappaB activation was found in the neurons
      with mutated Apaf-1 or a deletion of TNFRI compared with the cells from wild-type
      (WT) mice. Our studies suggest a novel neuronal response of Abeta, which occurs
      through a TNF receptor signaling cascade and a caspase-dependent death pathway.

PMID- 14973252
TI  - Dynamic gain control of dopamine delivery in freely moving animals.
AB  - Activity changes in a large subset of midbrain dopamine neurons fulfill numerous
      assumptions of learning theory by encoding a prediction error between actual and
      predicted reward. This computational interpretation of dopaminergic spike
      activity invites the important question of how changes in spike rate are
      translated into changes in dopamine delivery at target neural structures. Using
      electrochemical detection of rapid dopamine release in the striatum of freely
      moving rats, we established that a single dynamic model can capture all the
      measured fluctuations in dopamine delivery. This model revealed three independent
      short-term adaptive processes acting to control dopamine release. These short
      term components generalized well across animals and stimulation patterns and were
      preserved under anesthesia. The model has implications for the dynamic filtering
      interposed between changes in spike production and forebrain dopamine release.

PMID- 14973253
TI  - Differential effects of CB1 and opioid agonists on two populations of adult rat
      dorsal root ganglion neurons.
AB  - Inhibition of primary afferent neurons contributes to the antihyperalgesic
      effects of opioid and CB1 receptor agonists. Two bioassays were used to compare
      the effects of the CB1 receptor agonist CP 55,940 and morphine on dissociated
      adult rat DRG neurons. Both agonists inhibited the increase in free intracellular
      Ca2+ concentration evoked by depolarization; however, effects of CP 55,940
      occurred primarily in large neurons (cell area, >800 microm2), whereas morphine
      inhibited the response in smaller neurons. Cotreatment with selective blockers of
      L-, N-, and P/Q-type voltage-dependent Ca2+ channels indicated that CB1 receptors
      on DRG neurons couple solely with N-type channels but opioid receptors couple
      with multiple subtypes. Experiments with selective agonists and antagonists of
      opioid receptors indicated that mu and delta, but not kappa, receptors
      contributed to the inhibitory effect of morphine on voltage-dependent Ca2+
      influx. Because Ca2+ channels underlie release of transmitters from neurons, the
      effects of opioid agonists and CP 55,940 on depolarization-evoked release of
      calcitonin gene-related peptide (CGRP) were compared. Morphine inhibited release
      through delta receptors but CP 55,940 had no effect. Colocalization of CGRP with
      delta-opioid but not mu-opioid or CB1 receptor immunoreactivity in superficial
      laminae of the dorsal horn of the spinal cord was consistent with the data for
      agonist inhibition of peptide release. Therefore, CB1 and opioid agonists couple
      with different voltage-dependent Ca2+ channels in different populations of DRG
      neurons. Furthermore, differences occur in the distribution of receptors between
      the cell body and terminals of DRG neurons. The complementary action of CB1 and
      opioid receptor agonists on populations of DRG neurons provides a rationale for
      their combined use in modulation of somatosensory input to the spinal cord.

PMID- 14973254
TI  - P/Q-type Ca2+ channel alpha1A regulates synaptic competition on developing
      cerebellar Purkinje cells.
AB  - Synapse formation depends critically on the competition among inputs of multiple
      sources to individual neurons. Cerebellar Purkinje cells have highly organized
      synaptic wiring from two distinct sources of excitatory afferents. Single
      climbing fibers innervate proximal dendrites of Purkinje cells, whereas numerous
      parallel fibers converge on their distal dendrites. Here, we demonstrate that the
      P/Q-type Ca2+ channel alpha1A, a major Ca2+ channel subtype in Purkinje cells, is
      crucial for this organized synapse formation. In the alpha1A knock-out mouse,
      many ectopic spines were protruded from proximal dendrites and somata of Purkinje
      cells. Innervation territory of parallel fibers was expanded proximally to
      innervate the ectopic spines, whereas that of climbing fibers was regressed to
      the basal portion of proximal dendrites and somata. Furthermore, multiple
      climbing fibers consisting of a strong climbing fiber and one or a few weaker
      climbing fibers, persisted in the majority of Purkinje cells and were cowired to
      the same somata, proximal dendrites, or both. Therefore, the lack of alpha1A
      results in the persistence of parallel fibers and surplus climbing fibers, which
      should normally be expelled from the compartment innervated by the main climbing
      fiber. These results suggest that a P/Q-type Ca2+ channel alpha1A fuels
      heterosynaptic competition between climbing fibers and parallel fibers and also
      fuels homosynaptic competition among multiple climbing fibers. This molecular
      function facilitates the distal extension of climbing fiber innervation along the
      dendritic tree of the Purkinje cell and also establishes climbing fiber
      monoinnervation of individual Purkinje cells.

PMID- 14973255
TI  - Neural stem cell detection, characterization, and age-related changes in the
      subventricular zone of mice.
AB  - The mammalian brain contains neural stem cells (NSCs) that allow continued
      neurogenesis throughout the life of the animal. However, neurogenesis is known to
      decline during aging and, to the extent that neurogenesis is required for normal
      CNS function, this may contribute to neurodegenerative disease. Decreased
      neurogenesis could result from loss of NSCs or dysfunction at some later step,
      and distinguishing these possibilities is important for understanding the cause
      of the decline. However, because of the inability to distinguish NSCs from their
      rapidly dividing progeny in situ, it has not been possible to quantitatively
      assess the NSC populations in young and old animals. In this report we show that
      the G1 phase-specific expression of the replication factor Mcm2 is a useful
      marker for detecting slowly cycling putative NSCs in situ and confirm the
      identity of these cells using both cytosine beta-D-arabinofuranoside (Ara-C)
      treatment and a double nucleoside analog-labeling technique. The ability to
      distinguish NSCs from proliferative progenitors has allowed characterization of
      the expression of several markers including Nestin, Musashi, and GFAP in these
      different cell types. Furthermore, comparison of the NSC populations in the
      subventricular zones of young (2-4 months) and old (24-26 months) mice
      demonstrates an approximately twofold reduction in the older mice. A similar
      twofold reduction is also observed in the number of neurospheres recovered in
      culture from old relative to young animals. The reduction in the neural stem cell
      population documented here is sufficient to account for the reduced level of
      neurogenesis in old animals.

PMID- 14973256
TI  - Early expression of sodium channel transcripts and sodium current by cajal
      retzius cells in the preplate of the embryonic mouse neocortex.
AB  - In mouse, the first neurons are generated at embryonic day (E) 12 and form the
      preplate (PP), which contains a mix of future marginal zone cells, including
      Cajal-Retzius cells, and subplate cells. To detect developmental changes in
      channel populations in these earliest-generated neurons of the cerebral cortex,
      we studied the electrophysiological properties of proliferative cells of the
      ventricular zone and postmitotic neurons of the PP at E12 and E13, using whole
      cell patch-clamp recordings. We found an inward sodium current in 55% of PP
      cells. To determine whether sodium currents occur in a specific cell type, we
      stained recorded cells with an antibody for calretinin, a calcium-binding protein
      found specifically in Cajal-Retzius cells. All calretinin-positive cells had
      sodium currents, although so did some calretinin-negative cells. To correlate the
      Na current expression to Na channel gene expression with the Cajal-Retzius cell
      phenotype, we performed single-cell reverse transcription-PCR on patch-clamp
      recorded cells to detect expression of the Cajal-Retzius cell marker reelin and
      the Na channel isoforms SCN 1, 2, and 3. These results showed that virtually all
      Cajal-Retzius cells (97%), as judged by reelin expression, express the SCN
      transcript identified as the SCN3 isoform. Of these, 41% presented a functional
      Na current. There is, however, a substantial SCN-positive population in the PP
      (27% of SCN-positive cells) that does not express reelin. These results raise the
      possibility that populations of pioneer neurons of the PP, including Cajal
      Retzius cells, gain neuronal physiological properties early in development via
      expression of the Na(v)1.3 (SCN3) Na channel isoform.

PMID- 14973257
TI  - Interactions between androgen and growth factors in granulosa cell subtypes of
      porcine antral follicles.
AB  - Androgens acting via the androgen receptor (AR) have been implicated in
      regulation of folliculogenesis in many animal species. These effects are possibly
      mediated via enhancement of FSH and/or insulin-like growth factor (IGF)-I
      activity in granulosa cells, which contain high levels of AR protein. We examined
      the in vitro effect of dihydrotestosterone (DHT) on DNA synthesis and
      progesterone secretion by follicular cells in response to FSH and IGF-I, alone or
      in combination. Cells from separate pools of 1- to 3-mm and 3- to 5-mm antral
      follicles were aspirated from gilt ovaries and fractioned into mural granulosa
      cells (MGCs) and cumulus-oocyte complexes (COCs) for subsequent cell culture.
      Androgen alone or with any combination of mitogen had minimal effect on
      proliferative and no effect on steroidogenic responses of MGCs from 3- to 5-mm
      antral follicles. Conversely, in MGCs from 1- to 3-mm follicles, DHT
      significantly enhanced IFG-I-stimulated proliferation and had variable influence
      on progesterone secretion. The effects of DHT on proliferative responses of COCs
      were also dependent on follicle size: DHT significantly augmented either IGF-I
      stimulated proliferation (1- to 3-mm follicles) or FSH-stimulated proliferation
      (3- to 5-mm follicles). However, the steroidogenic responses of all COCs were
      identical, whereby DHT significantly suppressed progesterone secretion,
      predominantly in the presence of FSH. Addition of an AR antagonist,
      hydroxyflutamide, generally reversed the proliferative responses invoked by DHT
      but not the steroidogenic responses. We conclude that androgen-receptor-mediated
      activity in granulosa cells of antral follicles is dependent on follicle size, is
      influenced by proximity of cells to the oocyte, and possibly involves both
      classic and nonclassic steroid mechanisms.

PMID- 14973258
TI  - Steroid hormone modulation of prostaglandin secretion in the ruminant endometrium
      during the estrous cycle.
AB  - Prostaglandins, produced from membrane phospholipids by the action of
      phospholipase A2, cyclooxygenase, and specific prostaglandin synthases, are
      important regulators of ovulation, luteolysis, implantation, and parturition in
      reproductive tissues. Destruction of the corpus luteum at the end of the estrous
      cycle in nonpregnant animals is brought about by the pulsatile secretion of
      prostaglandin F(2alpha) (PGF(2alpha)) from the endometrium. It has been known for
      many years that progesterone, estradiol, and oxytocin are the hormones
      responsible for luteolysis. To achieve luteolysis, two independent processes have
      to be coordinated; the first is an increase in the prostaglandin synthetic
      capability of the endometrium and the second is an increase in oxytocin receptor
      number. Although progesterone and estradiol can modulate the expression of the
      enzymes involved in prostaglandin synthesis, the primary reason for the
      initiation of luteolysis is the increase in oxytocin receptor on the endometrial
      epithelial cells. Results of many in vivo studies have shown that progesterone
      and estradiol are required for luteolysis, but it is still not fully understood
      exactly how these steroid hormones act. The purpose of this article is to review
      the recent data related to how progesterone and estradiol could regulate
      (initiate and then turn off) the uterine pulsatile secretion of PGF(2alpha)
      observed at luteolysis.

PMID- 14973259
TI  - Effects of a gonadotropin-releasing hormone agonist implant on reproduction in a
      male marsupial, Macropus eugenii.
AB  - This study evaluated the potential of slow-release GnRH agonist (deslorelin)
      implants to inhibit reproductive function in the male tammar wallaby. The
      specific aim was to measure the effects of graded dosages of deslorelin on testes
      size and plasma LH and testosterone concentrations. Adult male tammar wallabies
      were assigned to four groups (n = 6 per group) and received the following
      treatment: control, placebo implant; low dose, 5 mg deslorelin; medium dose, 10
      mg; high dose, 20 mg. All dosages of deslorelin induced acute increases (P <
      0.001) in plasma LH and testosterone concentrations within 2 h, with
      concentrations remaining elevated during the first 24 h but returning to
      pretreatment levels by Day 7. Thereafter, there was no evidence of a treatment
      induced decline in plasma testosterone concentrations. There was no detectable
      difference in basal LH concentrations between treated and control animals, nor
      was there a significant change in testes width or length (P > 0.05). These
      results suggest that the male tammar wallaby is resistant to the contraceptive
      effects of chronic GnRH agonist treatment. Despite the maintenance of
      testosterone secretion, the majority of male tammars (10 of 17) failed to respond
      to a GnRH challenge with a release of LH between Days 186 and 197 of treatment.
      The failure of animals to respond to exogenous GnRH suggests a direct effect of
      deslorelin on the pituitary, resulting in a level of desensitization that was
      sufficient to inhibit a LH surge but insufficient to inhibit basal LH secretion.
      The variation between animals is believed to result from earlier recovery of some
      individuals, in particular those that received a lower dose, or individual
      resistance to the desensitization process.

PMID- 14973260
TI  - The expression of CXCR4/CXCL12 in first-trimester human trophoblast cells.
AB  - Chemokines and chemokine receptors have been implicated as pivotal players in
      many physiological and pathological situations, but little is known about the
      expression and function of chemokines and chemokine receptors at the materno
      fetal interface. In this study, we first analyzed the transcription of 18
      chemokine receptors in first-trimester human trophoblast cells. Among these
      receptors, CXCR4 was found highly transcribed. We demonstrated afterward that
      both CXCR4 and CXCL12 (stromal cell-derived factor-1; SDF-1) were expressed in
      trophoblast cells. Primary cultured trophoblast cells were also found secreting
      CXCL12 spontaneously. To identify the functional role of CXCR4/CXCL12 in these
      cells, we treated trophoblast cells with recombinant human (rh)SDF-1 alpha and
      analyzed the cell viability and signaling pathway. The results showed that rhSDF
      1 alpha increased the viability of trophoblast cells and the activation of
      extracellular signal-regulated kinases signaling pathway in vitro. Our findings
      suggest that first-trimester trophoblast cells express functional CXCR4/CXCL12,
      which may play an important role in early pregnancy such as stimulating
      trophoblast cell proliferation or differentiation in an autocrine manner.

PMID- 14973261
TI  - Cryopreservation induces an apoptosis-like mechanism in bull sperm.
AB  - Cryopreservation induces many changes in sperm cells, including membrane
      disorders and cell death. We tested the hypothesis that apoptosis, a form of
      programmed cell death, can contribute to the fatal effect of cryopreservation on
      sperm cells. A multiparametric study of apoptosis on bovine sperm is proposed,
      using flow cytometry, including mitochondrial membrane potential (DeltaPsi(m)),
      caspase activation, membrane permeability, nucleus condensation, DNA
      fragmentation, and phosphatidylserine (PS) externalization. The relevance of each
      test was first validated on a human somatic cell line, U937. Cryopreservation
      and/or thawing induced significant changes in all apoptotic markers in living
      bull sperm cells except those concerning the nucleus. After cryopreservation,
      44.9% +/- 17% (vs. 11.3% +/- 10.6% before cryopreservation) of sperm cells showed
      low DeltaPsi(m), 12% +/- 6.3% (vs. 2.2% +/- 1.0% before) contained active
      caspases, and 10.8% +/- 5.8% (vs. 1.4% +/- 1.1% before) exhibited high membrane
      permeability. However, cryopreservation had no effect on DNA fragmentation (9.1%
      +/- 7.7% before vs. 11.1% +/- 5.7% after cryopreservation) or on nucleus
      condensation (46% +/- 12.7% before vs. 43.8% +/- 13.1% after). Cryopreservation
      acts as an apoptotic mechanism inducer in bovine sperm cells, where the earliest
      but not the latest features of cells undergoing apoptosis occur. We have named
      this abortive process an apoptosis-like phenomenon.

PMID- 14973262
TI  - The premammillary hypothalamic area of the ewe: anatomical characterization of a
      melatonin target area mediating seasonal reproduction.
AB  - Recent evidence suggests that the ovine premammillary hypothalamic area (PMH) is
      an important target for the pineal hormone, melatonin, and its role in seasonal
      reproduction. In rodents, the PMH is a complex region consisting of several cell
      groups with differing neurochemical content and anatomical connections.
      Therefore, to obtain a better understanding of the potential neural targets for
      melatonin in this area of the sheep brain, we have undertaken a detailed
      anatomical characterization of the PMH, including its nuclear divisions and the
      location of neuropeptide/neurotransmitter cells within them. By combining
      immunocytochemistry for NeuN, a neuronal marker, with Nissl staining in
      anestrous, ovariectomized, estradiol-treated ewes, we identified three nuclei
      within the PMH: a caudal continuation of the hypothalamic arcuate nucleus (cARC),
      the ventral division of the premammillary nucleus (PMv), and the ventral
      tuberomammillary nucleus (TMv). The cARC contained neurons that were
      immunoreactive for tyrosine hydroxylase, dynorphin, estrogen receptor alpha,
      cocaine- and amphetamine-regulated transcript peptide (CART), and nitric oxide
      synthase (NOS). The PMv was also characterized by the presence of cells that
      contained NOS and CART, although the size of these cells was larger than that of
      their corresponding phenotype in the cARC. By contrast, in the TMv, of the
      markers examined in the present study, only fibers immunoreactive for orexin were
      seen. Thus, the ovine PMH is a heterogeneous region comprised of three
      subdivisions, each with distinct morphological and neurochemical characteristics.
      This anatomical map of the PMH provides a basis for future studies to determine
      the functional contribution of each component to the influence of melatonin on
      seasonal reproduction.

PMID- 14973263
TI  - Developmental dynamics of the definitive mouse placenta assessed by stereology.
AB  - The mouse is an excellent model for studying the genetic basis of placental
      development, but analyses are restricted by the lack of quantitative data
      describing normal murine placental structure. This study establishes a technique
      for generating such data, applies stereological techniques on systematic uniform
      random sections of placentas between E12.5-E18.5 of gestation (E1.0 = day of the
      vaginal plug), and considers the results in the context of development of the
      labyrinth zone. Half of each placenta was wax embedded and exhaustively sectioned
      to determine absolute volumes of the labyrinth zone (Lz), junctional zone (Jz),
      and decidua using the Cavalieri principle. The other half was resin embedded and
      1-microm sections were used to generate all volume, surface, and length densities
      within the Lz. Maximum placental volume is reached by E16.5, whereas the Lz
      volume fraction increases until E18.5 at the expense of the Jz and decidua.
      Within the Lz, the absolute volume and surface area of maternal blood spaces
      (MBS) expand rapidly between E14.5 and E16.5, with no increase thereafter. In
      contrast, fetal capillary development is linear and continues for longer than
      that of the MBS. The interhemal membrane separating maternal and fetal
      circulations undergoes thinning prior to expansion of maternal and fetal surface
      areas, achieving a harmonic mean thickness of 4.39 microm by E18.5. The specific
      diffusion capacity for oxygen of the interhemal membrane is maximal by E16.5,
      which may be necessary to support rapid fetal growth until the end of gestation.

PMID- 14973264
TI  - Progesterone and placental hormone actions on the uterus: insights from domestic
      animals.
AB  - Progesterone is unequivocally required for maternal support of conceptus
      (embryo/fetus and associated extraembryonic membranes) survival and development.
      In cyclic sheep, progesterone is paradoxically involved in suppressing and then
      initiating development of the endometrial luteolytic mechanism. In cyclic and
      pregnant sheep, progesterone negatively autoregulates progesterone receptor (PR)
      gene expression in the endometrial luminal (LE) and superficial glandular
      epithelium (GE). In cyclic sheep, PR loss is closely followed by increases in
      epithelial estrogen receptor (ERalpha) and then oxytocin receptor (OTR), allowing
      oxytocin to induce uterine release of luteolytic prostaglandin F2alpha pulses. In
      pregnant sheep, the conceptus produces interferon tau (IFNtau) that acts on the
      endometrium to inhibit transcription of the ERalpha gene and thus development of
      the endometrial luteolytic mechanism. After Day 13 of pregnancy, the endometrial
      epithelia do not express the PR, whereas the stroma and myometrium remain PR
      positive. The absence of PR in the endometrial GE is required for onset of
      differentiated function of the glands during pregnancy. The sequential,
      overlapping actions of progesterone, IFNtau, placental lactogen (PL), and growth
      hormone (GH) comprise a hormonal servomechanism that regulates endometrial gland
      morphogenesis and terminal differentiated function during gestation. In pigs,
      estrogen, the pregnancy-recognition signal, increases fibroblast growth factor 7
      (FGF-7) expression in the endometrial LE that, in turn, stimulates proliferation
      and differentiated functions of the trophectoderm, which expresses the receptor
      for FGF-7. Strategic manipulation of these physiological mechanisms may offer
      therapeutic schemes to improve uterine capacity, conceptus survival, and
      reproductive health of domestic animals and humans.

PMID- 14973265
TI  - The contribution of D-mannose, L-fucose, N-acetylglucosamine, and selectin
      residues on the binding of glycodelin isoforms to human spermatozoa.
AB  - Previous data showed that glycodelin-A from amniotic fluid and glycodelin-F from
      follicular fluid inhibited sperm-zona pellucida binding. Solubilized zona
      pellucida reduced the binding of glycodelin-F to sperm extract dose dependently.
      This study demonstrated that the zona pellucida proteins also reduced the binding
      of glycodelin-A to sperm extract. Ionophore-induced acrosome reaction reduced the
      binding of iodinated glycodelin-A and -F to sperm, indicating that the glycodelin
      binding sites are on the outer acrosomal membrane or on the sperm plasma membrane
      overlying the acrosome. While the binding of glycodelin-A to sperm was suppressed
      by mannose and fucose neoglycoproteins, that of glycodelin-F was also reduced by
      acetylglucosamine neoglycoprotein. Pretreatment of sperm with inhibitors of
      mannosidase and acetylglucosaminidase reduced the binding of glycodelin-F to
      sperm. On the other hand, inhibitor of mannosidase but not of
      acetylglucosaminidase inhibited the binding of glycodelin-A. In a competition
      binding assay, mannosidase reduced both glycodelin-A and -F binding whereas
      acetylglucosaminidase reduced only glycodelin-F binding. While fucosidase reduced
      the binding of both glycodelins, fucosidase inhibitor was marginally active in
      suppressing the binding of glycodelins to human sperm. Among the selectins
      tested, only E-selectin had a slight inhibitory effect on the binding of
      glycodelin-A to sperm. The binding of glycodelin-F was unaffected by selectins
      and their antibodies. In conclusion, the binding of glycodelin-A to sperm
      involves mannose, fucose, and possibly E- selectin residues, while that of
      glycodelin-F involves mannose, fucose, and N-acetylglucosamine but not the
      selectin residue.

PMID- 14973266
TI  - Formation and barrier function of tight junctions in human ovarian surface
      epithelium.
AB  - The normal ovarian surface epithelium (OSE) is a primitive epithelium made up by
      a single layer of mesothelial-type epithelial cells. When these cells get trapped
      in the ovarian stroma, expression of epithelial specific markers, such as E
      cadherin, are induced. Most epithelial cells are also characterized by the
      ability to form tight junctions (TJ). Incomplete TJ have earlier been
      demonstrated in the OSE by electron microscopy studies. We have investigated
      expression and localization of the TJ proteins ZO-1, occludin, and claudin-1 in
      tissue biopsies from normal human ovaries and OSE in culture. The dynamics of TJ
      formation were studied in human OSE cultured on porous filters in culture inserts
      by measuring trans epithelial resistance (TER) including Ca(2+) switch
      experiments. Confluent OSE cells were also analyzed by electron microscopy. The
      results show that normal human OSE has expression of all three TJ proteins
      investigated. These proteins, ZO-1, occludin, and claudin-1, were localized to
      OSE cell borders both in ovarian biopsies and in cultured OSE. There was no
      difference in this regard between fertile and postmenopausal women. Cells in
      culture were polarized and presented junctional complexes seen by electron
      microscopy. In the Ca(2+) switch experiments, removing free Ca(2+) transiently,
      TER decreased significantly (P < 0.05) in the Ca(2+)-free group compared with
      nontreated OSE. TER was fully restored after 24 h. N-cadherin but not E-cadherin
      was expressed in the OSE and localized to the cell borders. We conclude that
      normal human OSE express and form functional TJ both in vivo and vitro. This
      report also describes a method to study the influence of ovarian-derived
      mediators on TJ in cultured OSE.

PMID- 14973267
TI  - Methoxychlor-induced atresia in the mouse involves Bcl-2 family members, but not
      gonadotropins or estradiol.
AB  - Methoxychlor (MXC) is an organochlorine pesticide that increases the rate of
      ovarian atresia. To date, little is known about the mechanism by which MXC
      induces atresia. Because Bcl-2 (an antiapoptotic factor), Bax (a proapoptotic
      factor), gonadotropins, and estradiol are important regulators of atresia in the
      ovary, the purpose of this study was first to examine whether MXC-induced atresia
      occurred through alterations in Bcl-2 or Bax, and second, to examine the effect
      of MXC on gonadotropins, estradiol, and their receptors. CD-1 mice were dosed
      with 8-64 mg kg(-1) day(-1) MXC or vehicle (sesame oil). Ovaries were subjected
      to analysis of antral follicle numbers, Bcl-2, Bax, estrogen receptor, and
      follicle-stimulating hormone receptor levels. Blood was used to measure
      gonadotropins and estradiol. In some experiments, mice that overexpressed Bcl-2
      or mice that were deficient in Bax were dosed with MXC or vehicle and their
      ovaries were analyzed for atresia. MXC caused a dose-dependent increase in the
      percentage of atretic antral follicles compared with controls at the 32 and 64 mg
      kg(-1) day(-1) doses of MXC. MXC treatment did not result in changes in Bcl-2
      levels, but it did result in an increase in Bax levels in antral follicles. MXC
      treatment did not affect gonadotropin or estradiol levels, nor did it affect the
      levels of follicle-stimulating hormone or estrogen receptors. Mice that
      overexpressed Bcl-2 or mice that were deficient in Bax were protected from MXC
      induced atresia. These data suggest that MXC induces atresia through direct
      effects on the Bax and Bcl-2 signaling pathways in the ovary.

PMID- 14973268
TI  - robo2 and robo3 interact with eagle to regulate serotonergic neuron
      differentiation.
AB  - The function of the central nervous system (CNS) depends crucially upon the
      correct differentiation of neurons and formation of axonal connections. Some
      aspects of neuronal differentiation are known to occur as axonal connections are
      forming. Although serotonin is a highly conserved neurotransmitter that is
      important for many CNS functions, little is known about the process of
      serotonergic neuron differentiation. We show that in Drosophila, expression of
      the serotonin transporter (SerT) is both temporally and physically related to
      midline crossing. Additionally, we show that the axon guidance molecules
      roundabout2 and roundabout3 (robo2/3) are necessary for serotonergic neuron
      differentiation and function independently of their ligand, slit. Loss of robo2
      or robo3 causes a loss of SerT expression in about half of neurons, and resembles
      the phenotype seen in mutants for the transcription factor eagle (eg). Finally,
      we show a direct relationship between robo2/3 and eg: robo2/3 mutants lose Eg
      expression in serotonergic neurons, and robo2 and eg interact genetically to
      regulate SerT expression. We propose that post-midline expression of Robo2/3 is
      part of a signal that regulates serotonergic neuron differentiation and is
      transduced by the transcription factor Eg.

PMID- 14973269
TI  - Segmental development of reticulospinal and branchiomotor neurons in lamprey:
      insights into the evolution of the vertebrate hindbrain.
AB  - During development, the vertebrate hindbrain is subdivided along its
      anteroposterior axis into a series of segmental bulges called rhombomeres. These
      segments in turn generate a repeated pattern of rhombomere-specific neurons,
      including reticular and branchiomotor neurons. In amphioxus (Cephalochordata),
      the sister group of the vertebrates, a bona fide segmented hindbrain is lacking,
      although the embryonic brain vesicle shows molecular anteroposterior
      regionalization. Therefore, evaluation of the segmental patterning of the central
      nervous system of agnathan embryos is relevant to our understanding of the origin
      of the developmental plan of the vertebrate hindbrain. To investigate the
      neuronal organization of the hindbrain of the Japanese lamprey, Lethenteron
      japonicum, we retrogradely labeled the reticulospinal and branchial motoneurons.
      By combining this analysis with a study of the expression patterns of genes
      identifying specific rhombomeric territories such as LjKrox20, LjPax6, LjEphC and
      LjHox3, we found that the reticular neurons in the lamprey hindbrain, including
      isthmic, bulbar and Mauthner cells, develop in conserved rhombomere-specific
      positions, similar to those in the zebrafish. By contrast, lamprey trigeminal and
      facial motor nuclei are not in register with rhombomere boundaries, unlike those
      of gnathostomes. The trigeminal-facial boundary corresponds to the rostral border
      of LjHox3 expression in the middle of rhombomere 4. Exogenous application of
      retinoic acid (RA) induced a rostral shift of both the LjHox3 expression domain
      and branchiomotor nuclei with no obvious repatterning of rhombomeric segmentation
      and reticular neurons. Therefore, whereas subtype variations of motoneuron
      identity along the anteroposterior axis may rely on Hox-dependent positional
      values, as in gnathostomes, such variations in the lamprey are not constrained by
      hindbrain segmentation. We hypothesize that the registering of hindbrain
      segmentation and neuronal patterning may have been acquired through successive
      and independent stepwise patterning changes during evolution.

PMID- 14973270
TI  - De novo DNA methylation is dispensable for the initiation and propagation of X
      chromosome inactivation.
AB  - Xist (X-inactive specific transcript) plays a crucial role in X-inactivation.
      This non-coding RNA becomes upregulated on the X chromosome that is to be
      inactivated upon differentiation. Previous studies have revealed that although
      maintenance-type DNA methylation is not essential for X-inactivation to occur, it
      is required for the stable repression of Xist in differentiated cells. However,
      it is unknown whether differential de novo methylation at the Xist promoter,
      which is mediated by Dnmt3a and/or Dnmt3b, is a cause or a consequence of
      monoallelic expression of Xist. We show that Xist expression is appropriately
      regulated in the absence of Dnmt3a and Dnmt3b and that a single X chromosome
      undergoes proper inactivation in mutant females. Our results indicate that a
      mechanism(s) other than DNA methylation plays a principal role in initiating X
      inactivation. We also demonstrate that delayed upregulation of Xist does not
      induce X-inactivation, consistent with a crucial developmental window for the
      chromosomal silencing.

PMID- 14973271
TI  - Drosophila Twins regulates Armadillo levels in response to Wg/Wnt signal.
AB  - Protein Phosphatase 2A (PP2A) has a heterotrimeric-subunit structure, consisting
      of a core dimer of approximately 36 kDa catalytic and approximately 65 kDa
      scaffold subunits complexed to a third variable regulatory subunit. Several
      studies have implicated PP2A in Wg/Wnt signaling. However, reports on the precise
      nature of PP2A role in Wg/Wnt pathway in different organisms are conflicting. We
      show that twins (tws), which codes for the B/PR55 regulatory subunit of PP2A in
      Drosophila, is a positive regulator of Wg/Wnt signaling. In tws(-) wing discs
      both short- and long-range targets of Wingless morphogen are downregulated.
      Analyses of tws(-) mitotic clones suggest that requirement of Tws in Wingless
      pathway is cell-autonomous. Epistatic genetic studies indicate that Tws functions
      downstream of Dishevelled and upstream of Sgg and Armadillo. Our results suggest
      that Tws is required for the stabilization of Armadillo/beta-catenin in response
      to Wg/Wnt signaling. Interestingly, overexpression of, otherwise normal, Tws
      protein induce dominant-negative phenotypes. The conflicting reports on the role
      of PP2A in Wg/Wnt signaling could be due to the dominant-negative effect caused
      by the overexpression of one of the subunits.

PMID- 14973272
TI  - Sperm-induced modification of the oviductal gene expression profile after natural
      insemination in mice.
AB  - In mammals, the physiological interaction between spermatozoa and oviductal
      epithelia involves intimate and specific contact between the two cell types.
      Spermatozoa may undergo stringent selection processes within the female
      reproductive tract before they meet and fertilize oocytes. The physiological
      basis of the sperm selection process is largely unknown. Here we tested the
      hypothesis that the oviduct has a recognition system for spermatozoa that can
      detect the arrival of spermatozoa in the oviduct after insemination, resulting in
      alterations of the oviductal transcriptome. We initially performed a global
      screening of the oviductal transcriptome in mice 1) at the time of estrus
      (mating) and 2) 6 h after mating. Transcriptional alterations in the oviduct
      after mating were attributed to the presence of spermatozoa in the oviduct after
      mating and also to changes in the hormonal environment as female mice underwent
      the transition from estrus to diestrus. To distinguish these possibilities,
      female mice were then mated with T145H mutant mice, which because of
      spermatogenic arrest, produce seminal plasma but no spermatozoa. Focusing on two
      molecules that in the first experiment were upregulated after mating, it was
      found that adrenomedullin and prostaglandin endoperoxidase synthase 2 transcripts
      were upregulated in the oviducts of mice only after mating with fertile males;
      those mated with T145H infertile males showed significantly less response. These
      results indicate that it is the arrival of spermatozoa in the oviduct that
      activates one or more signal transduction pathways and leads to changes in the
      oviductal transcriptome profiles.

PMID- 14973273
TI  - C. elegans pro-1 activity is required for soma/germline interactions that
      influence proliferation and differentiation in the germ line.
AB  - Strict spatial and temporal regulation of proliferation and differentiation is
      essential for proper germline development and often involves soma/germline
      interactions. In C. elegans, a particularly striking outcome of defective
      regulation of the proliferation/differentiation pattern is the Pro phenotype in
      which an ectopic mass of proliferating germ cells occupies the proximal adult
      germ line, a region normally occupied by gametes. We describe a reduction-of
      function mutation in the gene pro-1 that causes a highly penetrant Pro phenotype.
      The pro-1 mutant Pro phenotype stems from defects in the time and position of the
      first meiotic entry during early germline development. pro-1(RNAi) produces a
      loss of somatic gonad structures and concomitant reduction in germline
      proliferation and gametogenesis. pro-1 encodes a member of a highly conserved
      subfamily of WD-repeat proteins. pro-1(+) is required in the sheath/spermatheca
      lineage of the somatic gonad in its role in the proper establishment of the
      proliferation/differentiation pattern in the germline. Our results provide a
      handle for further analysis of this soma-to-germline interaction.

PMID- 14973274
TI  - Metalloproteinase pregnancy-associated plasma protein A is a critical growth
      regulatory factor during fetal development.
AB  - Pregnancy-associated plasma protein A (PAPPA) is a metzincin superfamily
      metalloproteinase in the insulin-like growth factor (IGF) system. PAPPA increases
      IGF bioavailability and mitogenic effectiveness in vitro through regulated
      cleavage of IGF-binding protein 4 (IGFBP4). To determine its function in vivo, we
      generated PAPPA-null mice by gene targeting. Mice homozygous for targeted
      disruption of the PAPPA gene were viable but 60% the size of wild-type
      littermates at birth. The impact of the mutation was exerted during the early
      embryonic period prior to organogenesis, resulting in proportional dwarfism.
      PAPPA, IGF2 and IGFBP4 transcripts co-localized in wild-type embryos, and
      expression of IGF2 and IGFBP4 mRNA was not altered in PAPPA-deficient embryos.
      However, IGFBP4 proteolytic activity was completely lacking in fibroblasts
      derived from PAPPA-deficient embryos, and IGFBP4 effectively inhibited IGF
      stimulated mitogenesis in these cells. These results provide the first direct
      evidence that PAPPA is an essential growth regulatory factor in vivo, and suggest
      a novel mechanism for regulated IGF bioavailability during early fetal
      development.

PMID- 14973275
TI  - Target-derived BMP signaling limits sensory neuron number and the extent of
      peripheral innervation in vivo.
AB  - The role of target-derived BMP signaling in development of sensory ganglia and
      the sensory innervation of the skin was examined in transgenic animals that
      overexpress either the BMP inhibitor noggin or BMP4 under the control of a
      keratin 14 (K14) promoter. Overexpression of noggin resulted in a significant
      increase in the number of neurons in the trigeminal and dorsal root ganglia.
      Conversely, overexpression of BMP4 resulted in a significant decrease in the
      number of dorsal root ganglion neurons. There was no significant change in
      proliferation of trigeminal ganglion neurons in the noggin transgenic animals,
      and neuron numbers did not undergo the normal developmental decrease between
      E12.5 and the adult, suggesting that programmed cell death was decreased in these
      animals. The increase in neuron numbers in the K14-noggin animals was followed by
      an extraordinary increase in the density of innervation in the skin and a marked
      change in the pattern of innervation by different types of fibers. Conversely,
      the density of innervation of the skin was decreased in the BMP4 overexpressing
      animals. Further Merkel cells and their innervation were increased in the K14
      noggin mice and decreased in the K14-BMP4 mice. The changes in neuron numbers and
      the density of innervation were not accompanied by a change in the levels of
      neurotrophins in the skin. These findings indicate that the normal developmental
      decrease in neuron numbers in sensory ganglia depends upon BMP signaling, and
      that BMPs may limit both the final neuron number in sensory ganglia as well as
      the extent of innervation of targets. Coupled with prior observations, this
      suggests that BMP signaling may regulate the acquisition of dependence of neurons
      on neurotrophins for survival, as well as their dependence on target-derived
      neurotrophins for determining the density of innervation of the target.

PMID- 14973276
TI  - Gata2 specifies serotonergic neurons downstream of sonic hedgehog.
AB  - Distinct classes of serotonergic (5-HT) neurons develop along the ventral midline
      of the vertebrate hindbrain. Here, we identify a Sonic hedgehog (Shh)-regulated
      cascade of transcription factors that acts to generate a specific subset of 5-HT
      neurons. This transcriptional cascade is sufficient for the induction of rostral
      5-HT neurons within rhombomere 1 (r1), which project to the forebrain, but not
      for the induction of caudal 5-HT neurons, which largely terminate in the spinal
      cord. Within the rostral hindbrain, the Shh-activated homeodomain proteins Nkx2.2
      and Nkx6.1 cooperate to induce the closely related zinc-finger transcription
      factors Gata2 and Gata3. Gata2 in turn is necessary and sufficient to activate
      the transcription factors Lmx1b and Pet1, and to induce 5-HT neurons within r1.
      In contrast to Gata2, Gata3 is not required for the specification of rostral 5-HT
      neurons and appears unable to substitute for the loss of Gata2. Our findings
      reveal that the identity of closely related 5-HT subclasses occurs through
      distinct responses of adjacent rostrocaudal progenitor domains to broad ventral
      inducers.

PMID- 14973277
TI  - Active cell migration drives the unilateral movements of the anterior visceral
      endoderm.
AB  - The anterior visceral endoderm (AVE) of the mouse embryo is a specialised extra
      embryonic tissue that is essential for anterior patterning of the embryo. It is
      characterised by the expression of anterior markers such as Hex, Cerberus-like
      and Lhx1. At pre-gastrula stages, cells of the AVE are initially located at the
      distal tip of the embryo, but they then move unilaterally to the future anterior.
      This movement is essential for converting the existing proximodistal axis into an
      anteroposterior axis. To investigate this process, we developed a culture system
      capable of imaging embryos in real time with single cell resolution. Our results
      show that AVE cells continuously change shape and project filopodial processes in
      their direction of motion, suggesting that they are actively migrating. Their
      proximal movement stops abruptly at the junction of the epiblast and extra
      embryonic ectoderm, whereupon they move laterally. Confocal microscope images
      show that AVE cells migrate as a single layer in direct contact with the
      epiblast, suggesting that this tissue might provide directional cues. Together,
      these results show that the anteroposterior axis is correctly positioned by the
      active movement of cells of the AVE in response to cues from their environment,
      and by a 'barrier' to their movement that provides an endpoint for this
      migration.

PMID- 14973278
TI  - Early developmental failure of substantia nigra dopamine neurons in mice lacking
      the homeodomain gene Pitx3.
AB  - The mesencephalic dopamine (mesDA) system is involved in the control of movement
      and behavior. The expression of Pitx3 in the brain is restricted to the mesDA
      system and the gene is induced relatively late, at E11.5, a time when tyrosine
      hydroxylase (Th) gene expression is initiated. We show here that, in the Pitx3
      deficient aphakia (ak) mouse mutant, the mesDA system is malformed. Owing to the
      developmental failure of mesDA neurons in the lateral field of the midbrain,
      mesDA neurons are not found in the SNc and the projections to the caudate putamen
      are selectively lost. However, Pitx3 is expressed in all mesDA neurons in control
      animals. Therefore, mesDA neurons react specifically to the loss of Pitx3.
      Defects of motor control where not seen in the ak mice, suggesting that other
      neuronal systems compensate for the absence of the nigrostriatal pathway.
      However, an overall lower activity was observed. The results suggest that Pitx3
      is specifically required for the formation of the SNc subfield at the onset of
      dopaminergic neuron differentiation.

PMID- 14973279
TI  - Cytoplasmic and molecular reconstruction of Xenopus embryos: synergy of
      dorsalizing and endo-mesodermalizing determinants drives early axial patterning.
AB  - Ablation of vegetal cytoplasm from newly fertilized Xenopus eggs results in the
      development of permanent blastula-type embryos (PBEs). PBEs cleave normally and
      develop into a very simple tissue consisting only of atypical epidermis. We tried
      to restore complete embryonic development in PBEs by cytoplasmic transplantation
      or by mRNA injection. We show a two-step reconstruction of the body plan. In the
      first step, PBEs injected with either marginal cytoplasm or synthetic VegT RNA
      restored gastrulation and mesoderm formation, but not axial patterning. Injection
      of Xwnt8 mRNA (acting upstream of beta-catenin and thus substitutes for the
      dorsal determinant) did not restore axial development in PBEs. Simultaneous
      injections of Xwnt8 and VegT into PBEs resulted in dorsal axis development,
      showing the synergy of these molecules in axial development. These results
      suggest that the mixing of two cytoplasmic determinants, i.e. the dorsal
      determinant in the vegetal pole and the endo-mesodermal determinant in the whole
      vegetal half, triggers the early axial developmental process in Xenopus embryos.

PMID- 14973280
TI  - Upregulation of Mitimere and Nubbin acts through cyclin E to confer self-renewing
      asymmetric division potential to neural precursor cells.
AB  - In the Drosophila CNS, neuroblasts undergo self-renewing asymmetric divisions,
      whereas their progeny, ganglion mother cells (GMCs), divide asymmetrically to
      generate terminal postmitotic neurons. It is not known whether GMCs have the
      potential to undergo self-renewing asymmetric divisions. It is also not known how
      precursor cells undergo self-renewing asymmetric divisions. Here, we report that
      maintaining high levels of Mitimere or Nubbin, two POU proteins, in a GMC causes
      it to undergo self-renewing asymmetric divisions. These asymmetric divisions are
      due to upregulation of Cyclin E in late GMC and its unequal distribution between
      two daughter cells. GMCs in an embryo overexpressing Cyclin E, or in an embryo
      mutant for archipelago, also undergo self-renewing asymmetric divisions. Although
      the GMC self-renewal is independent of inscuteable and numb, the fate of the
      differentiating daughter is inscuteable and numb-dependent. Our results reveal
      that regulation of Cyclin E levels, and asymmetric distribution of Cyclin E and
      other determinants, confer self-renewing asymmetric division potential to
      precursor cells, and thus define a pathway that regulates such divisions. These
      results add to our understanding of maintenance and loss of pluripotential stem
      cell identity.

PMID- 14973281
TI  - The Arabidopsis JAGGED gene encodes a zinc finger protein that promotes leaf
      tissue development.
AB  - Important goals in understanding leaf development are to identify genes involved
      in pattern specification, and also genes that translate this information into
      cell types and tissue structure. Loss-of-function mutations at the JAGGED (JAG)
      locus result in Arabidopsis plants with abnormally shaped lateral organs
      including serrated leaves, narrow floral organs, and petals that contain fewer
      but more elongate cells. jag mutations also suppress bract formation in leafy,
      apetala1 and apetala2 mutant backgrounds. The JAG gene was identified by map
      based cloning to be a member of the zinc finger family of plant transcription
      factors and encodes a protein similar in structure to SUPERMAN with a single
      C(2)H(2)-type zinc finger, a proline-rich motif and a short leucine-rich
      repressor motif. JAG mRNA is localized to lateral organ primordia throughout the
      plant but is not found in the shoot apical meristem. Misexpression of JAG results
      in leaf fusion and the development of ectopic leaf-like outgrowth from both
      vegetative and floral tissues. Thus, JAG is necessary for proper lateral organ
      shape and is sufficient to induce the proliferation of lateral organ tissue.

PMID- 14973282
TI  - The role of JAGGED in shaping lateral organs.
AB  - Position-dependent regulation of growth is important for shaping organs in
      multicellular organisms. We have characterized the role of JAGGED, a gene that
      encodes a protein with a single C(2)H(2) zinc-finger domain, in controlling the
      morphogenesis of lateral organs in Arabidopsis thaliana. Loss of JAGGED function
      causes organs to have serrated margins. In leaves, the blade region is most
      severely affected. In sepals, petals and stamens, the strongest defects are seen
      in the distal regions. By monitoring cell-cycle activity in developing petals
      with the expression of HISTONE 4, we show that JAGGED suppresses the premature
      differentiation of tissues, which is necessary for the formation of the distal
      region. The localization of defects overlaps with the expression domain of
      JAGGED, which is restricted to the growing regions of lateral organs. JAGGED
      expression is notably absent from the cryptic bract, the remnant of a leaf-like
      organ that subtends the flower in many species but does not normally develop in
      wild-type Arabidopsis. If misexpressed, JAGGED can induce the formation of
      bracts, suggesting that the exclusion of JAGGED from the cryptic bract is a cause
      of bractless flowers in Arabidopsis.

PMID- 14973283
TI  - Overlapping and non-redundant functions of the Arabidopsis auxin response factors
      MONOPTEROS and NONPHOTOTROPIC HYPOCOTYL 4.
AB  - Transcription factors of the auxin response factor (ARF) family have been
      implicated in auxin-dependent gene regulation, but little is known about the
      functions of individual ARFs in plants. Here, interaction assays, expression
      studies and combinations of multiple loss- and gain-of-function mutants were used
      to assess the roles of two ARFs, NONPHOTOTROPIC HYPOCOTYL 4 (NPH4/ARF7) and
      MONOPTEROS (MP/ARF5), in Arabidopsis development. Both MP and NPH4 interact
      strongly and selectively with themselves and with each other, and are expressed
      in vastly overlapping domains. We show that the regulatory properties of both
      genes are far more related than suggested by their single mutant phenotypes. NPH4
      and MP are capable of controlling both axis formation in the embryo and auxin
      dependent cell expansion. Interaction of MP and NPH4 in Arabidopsis plants is
      indicated by their joint requirement in a number of auxin responses and by
      synergistic effects associated with the co-overexpression of both genes. Finally,
      we demonstrate antagonistic interaction between ARF and Aux/IAA gene functions in
      Arabidopsis development. Overexpression of MP suppresses numerous defects
      associated with a gain-of-function mutation in BODENLOS (BDL)/IAA12. Together
      these results provide evidence for the biological relevance of ARF-ARF and ARF
      Aux/IAA interaction in Arabidopsis plants and demonstrate that an individual ARF
      can act in both invariantly programmed pattern formation as well as in
      conditional responses to external signals.

PMID- 14973284
TI  - A Raf/MEK/ERK signaling pathway is required for development of the sea urchin
      embryo micromere lineage through phosphorylation of the transcription factor Ets.
AB  - In the sea urchin embryo, the skeleton of the larva is built from a population of
      mesenchymal cells known as the primary mesenchyme cells (PMCs). These derive from
      the large micromeres that originate from the vegetal pole at fourth cleavage. At
      the blastula stage, the 32 cells of this lineage detach from the epithelium and
      ingress into the blastocoel by a process of epithelial-mesenchymal transition. We
      report that shortly before ingression, there is a transient and highly localized
      activation of the MAP-kinase ERK in the micromere lineage. We show that
      ingression of the PMCs requires the activity of ERK, MEK and Raf, and depends on
      the maternal Wnt/beta-catenin pathway. Dissociation experiments and injection of
      mRNA encoding a dominant-negative form of Ras indicated that this activation is
      probably cell autonomous. We identified the transcription factors Ets1 and Alx1
      as putative targets of the phosphorylation by ERK. Both proteins contain a single
      consensus site for phosphorylation by the MAP kinase ERK. In addition, the Ets1
      protein sequence contains a putative ERK docking site. Overexpression of ets1 by
      injection of synthetic mRNA in the egg caused a dramatic increase in the number
      of cells becoming mesenchymal at the blastula stage. This effect could be largely
      inhibited by treating embryos with the MEK inhibitor U0126. Moreover, mutations
      in the consensus phosphorylation motif substituting threonine 107 by an aspartic
      or an alanine residue resulted respectively in a constitutively active form of
      Ets1 that could not be inhibited by U0126 or in an inactive form of Ets1. These
      results show that the MAP kinase pathway, working through phosphorylation of
      Ets1, is required for full specification of the PMCs and their subsequent
      transition from epithelial to mesenchymal state.

PMID- 14973285
TI  - Three putative murine Teashirt orthologues specify trunk structures in Drosophila
      in the same way as the Drosophila teashirt gene.
AB  - Drosophila teashirt (tsh) functions as a region-specific homeotic gene that
      specifies trunk identity during embryogenesis. Based on sequence homology, three
      tsh-like (Tsh) genes have been identified in the mouse. Their expression patterns
      in specific regions of the trunk, limbs and gut raise the possibility that they
      may play similar roles to tsh in flies. By expressing the putative mouse Tsh
      genes in flies, we provide evidence that they behave in a very similar way to the
      fly tsh gene. First, ectopic expression of any of the three mouse Tsh genes, like
      that of tsh, induces head to trunk homeotic transformation. Second, mouse Tsh
      proteins can rescue both the homeotic and the segment polarity phenotypes of a
      tsh null mutant. Third, following ectopic expression, the three mouse Tsh genes
      affect the expression of the same target genes as tsh in the Drosophila embryo.
      Fourth, mouse Tsh genes, like tsh, are able to induce ectopic eyes in adult
      flies. Finally, all Tsh proteins contain a motif that recruits the C-terminal
      binding protein and contributes to their repression function. As no other
      vertebrate or fly protein has been shown to induce such effects upon ectopic
      expression, these results are consistent with the idea that the three mouse Tsh
      genes are functionally equivalent to the Drosophila tsh gene when expressed in
      developing Drosophila embryos.

PMID- 14973286
TI  - Gibberellin regulates Arabidopsis floral development via suppression of DELLA
      protein function.
AB  - The phytohormone gibberellin (GA) regulates the development and fertility of
      Arabidopsis flowers. The mature flowers of GA-deficient mutant plants typically
      exhibit reduced elongation growth of petals and stamens. In addition, GA
      deficiency blocks anther development, resulting in male sterility. Previous
      analyses have shown that GA promotes the elongation of plant organs by opposing
      the function of the DELLA proteins, a family of nuclear growth repressors.
      However, it was not clear that the DELLA proteins are involved in the GA
      regulation of stamen and anther development. We show that GA regulates cell
      elongation rather than cell division during Arabidopsis stamen filament
      elongation. In addition, GA regulates the cellular developmental pathway of
      anthers leading from microspore to mature pollen grain. Genetic analysis shows
      that the Arabidopsis DELLA proteins RGA and RGL2 jointly repress petal, stamen
      and anther development in GA-deficient plants, and that this function is enhanced
      by RGL1 activity. GA thus promotes Arabidopsis petal, stamen and anther
      development by opposing the function of the DELLA proteins RGA, RGL1 and RGL2.

PMID- 14973287
TI  - HtrA1 serine protease inhibits signaling mediated by Tgfbeta family proteins.
AB  - HtrA1, a member of the mammalian HtrA serine protease family, has a highly
      conserved protease domain followed by a PDZ domain. Because HtrA1 is a secretory
      protein and has another functional domain with homology to follistatin, we
      examined whether HtrA1 functions as an antagonist of Tgfbeta family proteins.
      During embryo development, mouse HtrA1 was expressed in specific areas where
      signaling by Tgfbeta family proteins plays important regulatory roles. The GST
      pulldown assay showed that HtrA1 binds to a broad range of Tgfbeta family
      proteins, including Bmp4, Gdf5, Tgfbetas and activin. HtrA1 inhibited signaling
      by Bmp4, Bmp2, and Tgfbeta1 in C2C12 cells, presumably by preventing receptor
      activation. Experiments using a series of deletion mutants indicated that the
      binding activity of HtrA1 required the protease domain and a small linker region
      preceding it, and that inhibition of Tgfbeta signaling is dependent on the
      proteolytic activity of HtrA1. Misexpression of HtrA1 near the developing chick
      eye led to suppression of eye development that was indistinguishable from the
      effects of noggin. Taken together, these data indicate that HtrA1 protease is a
      novel inhibitor of Tgfbeta family members.

PMID- 14973288
TI  - missing oocyte encodes a highly conserved nuclear protein required for the
      maintenance of the meiotic cycle and oocyte identity in Drosophila.
AB  - In Drosophila, a single oocyte develops within a 16-cell germline cyst. Although
      all 16 cells initiate meiosis and undergo premeiotic S phase, only the oocyte
      retains its meiotic chromosome configuration and remains in the meiotic cycle.
      The other 15 cells in the cyst enter the endocycle and develop as polyploid nurse
      cells. A longstanding goal in the field has been to identify factors that are
      concentrated or activated in the oocyte, that promote meiotic progression and/or
      the establishment of the oocyte identity. We present the characterization of the
      missing oocyte gene, an excellent candidate for a gene directly involved in the
      differentiation of the oocyte nucleus. The missing oocyte gene encodes a highly
      conserved protein that preferentially accumulates in pro-oocyte nuclei in early
      prophase of meiosis I. In missing oocyte mutants, the oocyte enters the endocycle
      and develops as a polyploid nurse cell. Genetic interaction studies indicate that
      missing oocyte influences meiotic progression prior to pachytene and may interact
      with pathways that control DNA metabolism. Our data strongly suggest that the
      product of the missing oocyte gene acts in the oocyte nucleus to facilitate the
      execution of the unique cell cycle and developmental programs that produce the
      mature haploid gamete.

PMID- 14973289
TI  - Distinct activities of Msx1 and Msx3 in dorsal neural tube development.
AB  - Patterning of the dorsal neural tube involves Bmp signaling, which results in
      activation of multiple pathways leading to the formation of neural crest, roof
      plate and dorsal interneuron cell types. We show that constitutive activation of
      Bmp signaling at early stages (HH10-12) of chick neural tube development induces
      roof-plate cell fate, accompanied by an increase of programmed cell death and a
      repression of neuronal differentiation. These activities are mimicked by the
      overexpression of the homeodomain transcription factor Msx1, a factor known to be
      induced by Bmp signaling. By contrast, the closely related factor, Msx3, does not
      have these activities. At later stages of neural tube development (HH14-16),
      dorsal progenitor cells lose their competence to generate roof-plate cells in
      response to Bmp signaling and instead generate dorsal interneurons. This aspect
      of Bmp signaling is phenocopied by the overexpression of Msx3 but not Msx1. Taken
      together, these results suggest that these two different Msx family members can
      mediate distinct aspects of Bmp signaling during neural tube development.

PMID- 14973290
TI  - Transient requirement for ganglion cells during assembly of retinal synaptic
      layers.
AB  - The inner plexiform layer (IPL) of the vertebrate retina comprises functionally
      specialized sublaminae, representing connections between bipolar, amacrine and
      ganglion cells with distinct visual functions. Developmental mechanisms that
      target neurites to the correct synaptic sublaminae are largely unknown. Using
      transgenic zebrafish expressing GFP in subsets of amacrine cells, we imaged IPL
      formation and sublamination in vivo and asked whether the major postsynaptic
      cells in this circuit, the ganglion cells, organize the presynaptic inputs. We
      found that in the lak/ath5 mutant retina, where ganglion cells are never born,
      formation of the IPL is delayed, with initial neurite outgrowth ectopically
      located and grossly disorganized. Over time, the majority of early neurite
      projection errors are corrected, and major ON and OFF sublaminae do form.
      However, focal regions of disarray persist where sublaminae do not form properly.
      Bipolar axons, which arrive later, are targeted correctly, except at places where
      amacrine stratification is disrupted. The lak mutant phenotype reveals that
      ganglion cells have a transient role organizing the earliest amacrine projections
      to the IPL. However, it also suggests that amacrine cells interact with each
      other during IPL formation; these interactions alone appear sufficient to form
      the IPL. Furthermore, our results suggest that amacrines may guide IPL
      sublamination by providing stratification cues for other cell types.

PMID- 14973291
TI  - Bmp signals from niche cells directly repress transcription of a differentiation
      promoting gene, bag of marbles, in germline stem cells in the Drosophila ovary.
AB  - The Drosophila ovary is an attractive system to study how niches control stem
      cell self-renewal and differentiation. The niche for germline stem cells (GSCs)
      provides a Dpp/Bmp signal, which is essential for GSC maintenance. bam is both
      necessary and sufficient for the differentiation of immediate GSC daughters,
      cystoblasts. Here we show that Bmp signals directly repress bam transcription in
      GSCs in the Drosophila ovary. Similar to dpp, gbb encodes another Bmp niche
      signal that is essential for maintaining GSCs. The expression of phosphorylated
      Mad (pMad), a Bmp signaling indicator, is restricted to GSCs and some
      cystoblasts, which have repressed bam expression. Both Dpp and Gbb signals
      contribute to pMad production. bam transcription is upregulated in GSCs mutant
      for dpp and gbb. In marked GSCs mutant for Med and punt, two essential Bmp signal
      transducers, bam transcription is also elevated. Finally, we show that Med and
      Mad directly bind to the bam silencer in vitro. This study demonstrates that Bmp
      signals maintain the undifferentiated or self-renewal state of GSCs, and directly
      repress bam expression in GSCs by functioning as short-range signals. Thus, niche
      signals directly repress differentiation-promoting genes in stem cells in order
      to maintain stem cell self-renewal.

PMID- 14973292
TI  - Gbb/Bmp signaling is essential for maintaining germline stem cells and for
      repressing bam transcription in the Drosophila testis.
AB  - Stem cells are responsible for replacing damaged or dying cells in various adult
      tissues throughout a lifetime. They possess great potential for future
      regenerative medicine and gene therapy. However, the mechanisms governing stem
      cell regulation are poorly understood. Germline stem cells (GSCs) in the
      Drosophila testis have been shown to reside in niches, and thus these represent
      an excellent system for studying relationships between niches and stem cells.
      Here we show that Bmp signals from somatic cells are essential for maintaining
      GSCs in the Drosophila testis. Somatic cyst cells and hub cells express two Bmp
      molecules, Gbb and Dpp. Our genetic analysis indicates that gbb functions
      cooperatively with dpp to maintain male GSCs, although gbb alone is essential for
      GSC maintenance. Furthermore, mutant clonal analysis shows that Bmp signals
      directly act on GSCs and control their maintenance. In GSCs defective in Bmp
      signaling, expression of bam is upregulated, whereas forced bam expression in
      GSCs causes the GSCs to be lost. This study demonstrates that Bmp signals from
      the somatic cells maintain GSCs, at least in part, by repressing bam expression
      in the Drosophila testis. dpp signaling is known to be essential for maintaining
      GSCs in the Drosophila ovary. This study further suggests that both Drosophila
      male and female GSCs use Bmp signals to maintain GSCs.

PMID- 14973293
TI  - Newborn horizontal cells migrate bi-directionally across the neuroepithelium
      during retinal development.
AB  - Cell migration plays an important role during the development of the retina. In
      this work we have studied the migration of newborn horizontal cells in avian
      embryonic retina. Using the pattern of the early expressed transcription factors
      Lim1 and Prox1 we have shown that horizontal cells migrate bi-directionally from
      their site of birth, close to the ventricular side, to the adjacent (vitreal)
      side of the neuroepithelium, where they align just next to the prospective
      ganglion cell layer before migrating back again to their final laminar position
      in the external part of the inner nuclear layer. The migration occurs between
      Hamburger and Hamilton stages 24 and 33, which is equivalent to embryonic day 4.5
      and 8. Between stages 26 and 30 the horizontal cells reside close to the ganglion
      cell layer and intra ocular injections of a cytochalasin D, an actin
      polymerisation blocker that inhibit migration, at stage 29 interfered with the
      migration of the horizontal cells to their final destination. Furthermore, using
      biolistic gene transfer with a green fluorescence protein expression vector of
      retinal slices we were able to record ventricle-directed migration by time-lapse
      microscopy. Combining biolistics with immunohistochemistry we showed that
      transfected cells, which have also been translocated in a ventricular direction
      were positive for the horizontal cell markers Lim1 and Prox1. The alternative
      path of migration that is described in this work differs from the generally
      accepted one for horizontal cells and this knowledge will influence the view of
      how the molecular determination of horizontal cells is specified.

PMID- 14973294
TI  - Bapx1 regulates patterning in the middle ear: altered regulatory role in the
      transition from the proximal jaw during vertebrate evolution.
AB  - The middle ear apparatus is composed of three endochondrial ossicles (the stapes,
      incus and malleus) and two membranous bones, the tympanic ring and the gonium,
      which act as structural components to anchor the ossicles to the skull. Except
      for the stapes, these skeletal elements are unique to mammals and are derived
      from the first and second branchial arches. We show that, in combination with
      goosecoid (Gsc), the Bapx1 gene defines the structural components of the murine
      middle ear. During embryogenesis, Bapx1 is expressed in a discrete domain within
      the mandibular component of the first branchial arch and later in the primordia
      of middle ear-associated bones, the gonium and tympanic ring. Consistent with the
      expression pattern of Bapx1, mouse embryos deficient for Bapx1 lack a gonium and
      display hypoplasia of the anterior end of the tympanic ring. At E10.5, expression
      of Bapx1 partially overlaps that of Gsc and although Gsc is required for
      development of the entire tympanic ring, the role of Bapx1 is restricted to the
      specification of the gonium and the anterior tympanic ring. Thus, simple
      overlapping expression of these two genes appears to account for the patterning
      of the elements that compose the structural components of the middle ear and
      suggests that they act in concert. In addition, Bapx1 is expressed both within
      and surrounding the incus and the malleus. Examination of the malleus shows that
      the width, but not the length, of this ossicle is decreased in the mutant mice.
      In non-mammalian jawed vertebrates, the bones homologous to the mammalian middle
      ear ossicles compose the proximal jaw bones that form the jaw articulation
      (primary jaw joint). In fish, Bapx1 is responsible for the formation of the joint
      between the quadrate and articular (homologues of the malleus and incus,
      respectively) enabling an evolutionary comparison of the role of a regulatory
      gene in the transition of the proximal jawbones to middle ear ossicles. Contrary
      to expectations, murine Bapx1 does not affect the articulation of the malleus and
      incus. We show that this change in role of Bapx1 following the transition to the
      mammalian ossicle configuration is not due to a change in expression pattern but
      results from an inability to regulate Gdf5 and Gdf6, two genes predicted to be
      essential in joint formation.

PMID- 14973295
TI  - Discrete gene sets depend on POU domain transcription factor Brn3b/Brn-3.2/POU4f2
      for their expression in the mouse embryonic retina.
AB  - Brn3b/Brn-3.2/POU4f2 is a POU domain transcription factor that is essential for
      retinal ganglion cell (RGC) differentiation, axonal outgrowth and survival. Our
      goal was to establish a link between Brn3b and the downstream events leading to
      RGC differentiation. We sought to determine both the number and types of genes
      that depend on Brn3b for their expression. RNA probes from wild-type and Brn3b(-/
      ) E14.5, E16.5 and E18.5 mouse retinas were hybridized to a microarray containing
      18,816 retina-expressed cDNAs. At E14.5, we identified 87 genes whose expression
      was significantly altered in the absence of Brn3b and verified the results by
      real-time PCR and in situ hybridization. These genes fell into discrete sets that
      encoded transcription factors, proteins associated with neuron integrity and
      function, and secreted signaling molecules. We found that Brn3b influenced gene
      expression in non RGCs of the retina by controlling the expression of secreted
      signaling molecules such as sonic hedgehog and myostatin/Gdf8. At later
      developmental stages, additional alterations in gene expression were secondary
      consequences of aberrant RGC differentiation caused by the absence of Brn3b. Our
      results demonstrate that a small but crucial fraction of the RGC transcriptome is
      dependent on Brn3b. The Brn3b-dependent gene sets therefore provide a unique
      molecular signature for the developing retina.

PMID- 14973296
TI  - Reiterated Wnt signaling during zebrafish neural crest development.
AB  - While Wnt/beta-catenin signaling is known to be involved in the development of
      neural crest cells in zebrafish, it is unclear which Wnts are involved, and when
      they are required. To address these issues we employed a zebrafish line that was
      transgenic for an inducible inhibitor of Wnt/beta-catenin signaling, and
      inhibited endogenous Wnt/beta-catenin signaling at discrete times in development.
      Using this approach, we defined a critical period for Wnt signaling in the
      initial induction of neural crest, which is distinct from the later period of
      development when pigment cells are specified from neural crest. Blocking Wnt
      signaling during this early period interfered with neural crest formation without
      blocking development of dorsal spinal neurons. Transplantation experiments
      suggest that neural crest precursors must directly transduce a Wnt signal. With
      regard to identifying which endogenous Wnt is responsible for this initial
      critical period, we established that wnt8 is expressed in the appropriate time
      and place to participate in this process. Supporting a role for Wnt8, blocking
      its function with antisense morpholino oligonucleotides eliminates initial
      expression of neural crest markers. Taken together, these results demonstrate
      that Wnt signals are critical for the initial induction of zebrafish neural crest
      and suggest that this signaling pathway plays reiterated roles in its
      development.

PMID- 14973297
TI  - Ihh signaling is directly required for the osteoblast lineage in the endochondral
      skeleton.
AB  - Indian hedgehog (Ihh) is indispensable for development of the osteoblast lineage
      in the endochondral skeleton. In order to determine whether Ihh is directly
      required for osteoblast differentiation, we have genetically manipulated
      smoothened (Smo), which encodes a transmembrane protein that is essential for
      transducing all Hedgehog (Hh) signals. Removal of Smo from perichondrial cells by
      the Cre-LoxP approach prevents formation of a normal bone collar and also
      abolishes development of the primary spongiosa. Analysis of chimeric embryos
      composed of wild-type and Smo(n/n) cells indicates that Smo(n/n) cells fail to
      contribute to osteoblasts in either the bone collar or the primary spongiosa but
      generate ectopic chondrocytes. In order to assess whether Ihh is sufficient to
      induce bone formation in vivo, we have analyzed the bone collar in the long bones
      of embryos in which Ihh was artificially expressed in all chondrocytes by the UAS
      GAL4 bigenic system. Although ectopic Ihh does not induce overt ossification
      along the entire cartilage anlage, it promotes progression of the bone collar
      toward the epiphysis, suggesting a synergistic effect between ectopic Ihh and
      endogenous factors such as the bone morphogenetic proteins (BMPs). In keeping
      with this model, Hh signaling is further found to be required in BMP-induced
      osteogenesis in cultures of a limb-bud cell line. Taken together, these results
      demonstrate that Ihh signaling is directly required for the osteoblast lineage in
      the developing long bones and that Ihh functions in conjunction with other
      factors such as BMPs to induce osteoblast differentiation. We suggest that Ihh
      acts in vivo on a potential progenitor cell to promote osteoblast and prevent
      chondrocyte differentiation.

PMID- 14973298
TI  - Notch signaling: control of cell communication and cell fate.
AB  - Notch is a transmembrane receptor that mediates local cell-cell communication and
      coordinates a signaling cascade present in all animal species studied to date.
      Notch signaling is used widely to determine cell fates and to regulate pattern
      formation; its dysfunction results in a tremendous variety of developmental
      defects and adult pathologies. This primer describes the mechanism of Notch
      signal transduction and how it is used to control the formation of biological
      patterns.

PMID- 14973299
TI  - Similarity of insulin detemir pharmacokinetics, safety, and tolerability profiles
      in healthy caucasian and Japanese american subjects.
AB  - The objective of this study was to compare the pharmacokinetics of insulin
      detemir in three ascending doses in healthy Japanese and Caucasian subjects. This
      was an open-label, single-center, parallel-group design evaluating 30 subjects
      (15 Japanese and 15 Caucasians). Subjects received a total of three subcutaneous
      injections (one injection per visit) of insulin detemir (0.19, 0.38, 0.75 U/kg [1
      U = 24 nmol]) in ascending order. Following drug administration, subjects
      received intravenous glucose in 0.5-mg/kg/min increments every 30 minutes,
      followed by a constant rate of 2.0 mg/kg/min for up to 12 hours. For
      pharmacokinetic evaluations, serial blood sampling was performed over a period of
      30 hours after dosing. Of the subjects, 36 were enrolled, and 30 completed the
      study. There was a linear dose-response relationship between the three ascending
      insulin detemir doses and serum insulin detemir AUC values for both the Japanese
      and Caucasian subjects. The two dose-response regression lines had equivalent
      slopes but slightly different intercepts (although not statistically
      significant). This difference may be due to variation in AUC, body weight
      differences, or chance. Six subjects discontinued the study, 2 as a result of
      adverse events (blood draw-related ecchymosis and hypoglycemia). The most
      frequent treatment-emergent adverse events (TEAE) were headache, dizziness, and
      reactions related to blood draws/infusion sites. All TEAEs were mild to moderate
      in severity. The results show that an increase in insulin detemir dose will
      result in a similar increase in insulin detemir concentration in the two ethnic
      groups. Therefore, therapeutic dosing of insulin detemir is expected to be
      similar in both ethnic groups, with no special dose adjustment or algorithm based
      on race. Insulin detemir at 0.19, 0.38, and 0.75 U/kg was generally well
      tolerated in both Japanese and Caucasian subjects.

PMID- 14973300
TI  - The pharmacokinetics of sodium oxybate oral solution following acute and chronic
      administration to narcoleptic patients.
AB  - This trial was conducted to evaluate the pharmacokinetics and safety of a sodium
      oxybate (gamma-hydroxybutyrate [GHB]) oral solution in narcoleptic patients after
      acute and chronic treatment. An open-label, two-period, two-treatment study
      design was used. Trial subjects included 13 patients with polysomnographically
      confirmed narcolepsy. The patients were administered a bedtime dose of 4.5 g of
      sodium oxybate while in a sleep research center. They were subsequently treated
      with sodium oxybate at the nightly dose of 4.5 g for 8 weeks. The patients then
      returned to the sleep center and were again treated with the 4.5-g sodium oxybate
      dose at bedtime. Blood samples (5 mL) were collected at 18 time points before and
      up to 7 hours after both the first dose of sodium oxybate and following 8 weeks
      of dosing. Plasma samples were analyzed for oxybate content by a validated liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) method. Noncompartmental
      methods were applied in the determination of pharmacokinetic parameters from each
      patient's plasma oxybate concentration versus time curve. No serious adverse
      events were recorded, and all patients completed the study. Headache, enuresis,
      and leg cramps were reported as adverse experiences. With both acute and chronic
      dosing, sodium oxybate was rapidly absorbed and eliminated with an apparent half
      life of about 40 minutes. The only changes observed in the kinetics of oxybate
      after 8 weeks of treatment were a 13% and 16% increase in peak concentration
      (C(max)) and systemic exposure (AUC), respectively. The pharmacokinetics of
      sodium oxybate in narcoleptic patients were not changed in any clinically
      significant manner when the drug was chronically administered. The drug was well
      tolerated.

PMID- 14973301
TI  - Rheumatoid arthritis does not reduce the pharmacodynamic response to valsartan.
AB  - Inflammatory conditions decrease the cardiovascular response to calcium channel
      and beta-adrenergics blockers due, likely, to down-regulation of the receptors
      mediated by pro-inflammatory mediators such as C-reactive protein (CRP), nitric
      oxide (NO), and tumor necrosis factor. The purpose of this investigation was to
      determine whether down-regulation is also evident in angiotensin II type 1
      receptors (AT(1)R) during varying inflammatory states. Normotensive subjects were
      divided into three groups according to the severity of disease: 14 with active
      rheumatoid arthritis, 12 with controlled rheumatoid arthritis, and 12 healthy
      control subjects. The AT(1)R antagonist valsartan (160 mg) was given to all the
      subjects, and blood samples were taken for pharmacokinetic analysis. The
      systolic, diastolic, and mean arterial pressures were determined at all blood
      collection times. The degree of inflammation was measured using joint swelling,
      NO, and CRP. Plasma valsartan concentration was measured using high-performance
      liquid chromatography (HPLC). Patients with active disease had significantly
      higher joint swelling, NO, and CRP than other groups. Plasma valsartan
      concentration-time curves were remarkably similar in all groups. No reduced
      response was noticed. Our preliminary observation suggests a need for further
      studies to examine the possibility of AT(1)R antagonists as alternatives to other
      cardiovascular drugs so that their potency may be reduced by inflammation.

PMID- 14973302
TI  - Pharmacokinetics and safety of the ketolide telithromycin in patients with renal
      impairment.
AB  - The pharmacokinetics and safety of the ketolide telithromycin were evaluated in
      two separate studies after single and repeat oral dosing in patients with varying
      degrees of renal impairment and in subjects with normal renal function. The
      single-dose study was an open-label, nonrandomized, parallel-group design in
      which all 40 patients received a single oral dose of telithromycin 800 mg. The
      repeat-dose study was an open-label study with a randomized, balanced, incomplete
      three-block treatment crossover design. In this study, each of the 36 patients
      received two of three telithromycin regimens (400, 600, or 800 mg once daily for
      5 days), with a washout period of >/= 7 days between treatments. Telithromycin
      was well tolerated. Adverse events were generally mild in severity, and no
      serious drug-related adverse events were reported. Plasma exposure to
      telithromycin (C(max), AUC) showed a tendency to increase with increasing
      severity of renal impairment in both studies. In patients with severe renal
      impairment (CL(CR) < 30 mL/min) receiving telithromycin 800 mg in the repeat-dose
      study, C(max,ss) and AUC((0-24 h)ss) increased 1.5-fold (p < 0.05) to 2.0-fold (p
      = 0.0005), respectively, compared with healthy subjects. The percentage of dose
      excreted in urine and renal clearance (CL(R)) of telithromycin was found to
      decrease significantly with increasing severity of renal impairment in both
      studies, and CL(R) was found to be independent of telithromycin dose in the
      repeat-dose study. In conclusion, telithromycin dosage adjustment is not
      necessary in patients with mild to moderate renal impairment (CL(CR) >/= 30
      mL/min). In patients with severe renal impairment (CL(CR) < 30 mL/min), dosage
      adjustment could be considered.

PMID- 14973303
TI  - Quinidine as a probe for the role of p-glycoprotein in the intestinal absorption
      and clinical effects of fentanyl.
AB  - The mechanism of individual variability in the fentanyl dose-effect relationship
      is unknown. The efflux pump P-glycoprotein (P-gp) regulates brain access and
      intestinal absorption of numerous drugs. Evidence exists that fentanyl is a P-gp
      substrate in vitro, and P-gp affects fentanyl analgesia in animals. However, the
      role of P-gp in human fentanyl disposition and clinical effects is unknown. This
      investigation tested the hypothesis that plasma concentrations and clinical
      effects of oral and intravenous fentanyl are greater after inhibition of
      intestinal and brain P-gp, using the P-gp inhibitor quinidine as an in vivo
      probe. Two randomized, double-blind, placebo-controlled, balanced, two-period
      crossover studies were conducted in normal healthy volunteers (6 males and 6
      females) after obtaining informed consent. Pupil diameters and/or plasma
      concentrations of fentanyl and norfentanyl were evaluated after oral or
      intravenous fentanyl (2.5 microg/kg), dosed 1 hour after oral quinidine (600 mg)
      or placebo. Quinidine did not alter the magnitude or time to maximum miosis, time
      specific pupil diameter, or subjective self-assessments after intravenous
      fentanyl but did increase the area under the curve (AUC) of miosis versus time
      (13.6 +/- 5.3 vs. 8.7 +/- 5.0 mm*h, p< 0.05) and decreased the effect of
      elimination (k(el) 0.35 +/- 0.16 vs. 0.52 +/- 0.24 h(-1), p < 0.05). Quinidine
      increased oral fentanyl plasma C(max) (0.55 +/- 0.19 vs. 0.21 +/- 0.1 ng/mL) and
      AUC (1.9 +/- 0.5 vs. 0.7 +/- 0.3 ng*h*mL(-1)) (both p < 0.05) but had no effect
      on apparent elimination. Plasma norfentanyl/fentanyl AUC ratios were not
      diminished by quinidine. Quinidine significantly increased maximum miosis after
      oral fentanyl (3.4 +/- 1.3 vs. 2.3 +/- 1.3 mm, p< 0.05), commensurate with
      increases in plasma concentrations, but concentration-effect relationships and
      the rate constant for the transfer between plasma and effect compartment (k(e0))
      (1.9 +/- 1.0 vs. 3.6 +/- 2.6 h(-1)) were not significantly different. Quinidine
      increased oral fentanyl plasma concentrations, suggesting that intestinal P-gp or
      some other quinidine-sensitive transporter affects the absorption,
      bioavailability, and hence clinical effects of oral fentanyl. Quinidine had less
      effect on fentanyl pharmacodynamics, suggesting that if quinidine is an effective
      inhibitor of brain P-gp, then P-gp appears to have less effect on brain access of
      fentanyl.

PMID- 14973304
TI  - Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4
      and 2C9 activity.
AB  - The NK(1) receptor antagonist aprepitant (EMEND(R)), developed for use in
      combination with a 5HT(3) receptor antagonist and a corticosteroid to prevent
      highly emetogenic chemotherapy-induced nausea and vomiting (CINV), has been shown
      to have a moderate inhibitory effect as well as a possible inductive effect on
      cytochrome P450 (CYP) 3A4. Aprepitant has been noted to produce modest decreases
      in plasma S(-)-warfarin concentrations, suggesting potential induction of CYP2C9.
      Because metabolism of some chemotherapeutic agents may involve CYP3A4, the
      potential inductive effect of the CINV dosing regimen of aprepitant on this
      metabolic pathway was evaluated using intravenous midazolam, a sensitive probe
      substrate of CYP3A4. The time course of induction of CYP2C9 by aprepitant was
      also evaluated using oral tolbutamide, a probe substrate of CYP2C9. In this
      double-blind, randomized, placebo-controlled, single-center study, 24 healthy
      subjects were randomized (12 subjects per group) to receive either an aprepitant
      3-day regimen (aprepitant 125 mg p.o. on day 1 and aprepitant 80 mg p.o. on days
      2 and 3) or matching placebo. All subjects also received probe drugs (midazolam 2
      mg i.v. and tolbutamide 500 mg p.o.) once prior to aprepitant dosing (baseline)
      and again on days 4, 8, and 15. The ratio (aprepitant/placebo) of the geometric
      mean area under the plasma concentration curve (AUC) fold-change from baseline
      for midazolam was 1.25 on day 4 (p < 0.01), 0.81 on day 8 (p < 0.01), and 0.96 on
      day 15 (p = 0.646). The ratio (aprepitant/placebo) of the geometric mean AUC fold
      change from baseline for tolbutamide was 0.77 on day 4 (p < 0.01), 0.72 on day 8
      (p < 0.001), and 0.85 on day 15 (p = 0.05). Assessed using intravenous midazolam
      as a probe, aprepitant 125/80 mg p.o. administered over days 1 to 3 produced
      clinically insignificant weak inhibition (day 4) and induction (day 8) of CYP3A4
      activity and no effect on CYP3A4 activity on day 15. Assessed using oral
      tolbutamide as a probe, the aprepitant regimen also produced modest induction of
      CYP2C9 activity on days 4 and 8, which resolved nearly to baseline by day 15.
      Thus, the aprepitant regimen for CINV results in modest, transient induction of
      CYPs 3A4 and 2C9 in the 2 weeks following administration.

PMID- 14973305
TI  - Indinavir and rifabutin drug interactions in healthy volunteers.
AB  - Two studies examined the pharmacokinetics of indinavir and rifabutin when
      coadministered in healthy subjects. Rifabutin, which induces the expression of
      cytochrome P450 (CYP) 3A, and indinavir, which inhibits that enzyme system, are
      frequently coadministered in patients infected with HIV. The second study was
      undertaken to determine if altering the dose of rifabutin coadministered with
      indinavir would minimize the drug interaction observed in the first study. Two
      studies, each with a three-period crossover design, were performed. In study 1,
      standard doses of rifabutin and indinavir (300 mg of rifabutin qd and 800 mg
      indinavir q8h) were administered as monotherapy (with placebo to the other drug)
      or in combination to 10 volunteers for 10 days. In study 2, 150 mg qd of
      rifabutin together with 800 mg q8h of indinavir, 300 mg qd of rifabutin alone, or
      800 mg q8h of indinavir alone was administered to 14 volunteers for 10 days. In
      study 1, the geometric mean ratio (GMR) (90% confidence interval [CI]) of the
      AUC((0-8h)) of indinavir, coadministered with rifabutin 300 mg qd compared to
      indinavir alone (with rifabutin placebo), was 0.66 (0.56, 0.77), while that of
      the AUC((0-24h)) of rifabutin, coadministered with indinavir compared to
      rifabutin alone (with indinavir placebo), was 2.73 (1.99, 3.77). In study 2, the
      GMR (90% CI) of the AUC((0-8h)) of indinavir, coadministered with rifabutin 150
      mg qd compared to indinavir alone, was 0.68 (0.60, 0.76), while that of the
      AUC((0-24h)) of rifabutin, when rifabutin 150 mg qd was coadministered with
      indinavir compared to rifabutin 300 mg qd alone, was 1.54 (1.33, 1.79). For both
      studies 1 and 2, indinavir and rifabutin administered alone or in combination
      were generally well tolerated. No clinical or laboratory adverse experience was
      serious. These data demonstrate the important pharmacokinetic interactions
      between indinavir and rifabutin when they are coadministered. Indeed, these
      observations formed the basis for the subsequent ACTG 365 study that explored
      dose adjustments for these agents in combination regimens to preserve the
      sustained antiviral activity of indinavir in the absence of adverse events as a
      result of elevated circulating levels of rifabutin.

PMID- 14973306
TI  - The effects of once-daily saquinavir/minidose ritonavir on the pharmacokinetics
      of methadone.
AB  - Twelve methadone-maintained HIV-negative subjects were given saquinavir/ritonavir
      (SQV/rtv) 1600 mg/100 mg once daily for 14 days. Pharmacokinetic evaluations of
      total and unbound methadone enantiomers (R and S) were conducted before and after
      SQV/rtv. SQV/rtv was well tolerated, with no ACTG Grade 3-4 adverse events, no
      evidence of sedation, and no changes in methadone dose. For R-methadone (active
      isomer), C(max), AUC(0-24 h), and C(min) were unchanged, but percent unbound 4
      hours after dosing was reduced by 12%. For S-methadone, no differences in
      pharmacokinetic parameters of total drug were seen, but unbound concentrations
      were reduced by 15% and 21% at 4 and 24 hours after dosing, respectively. SQV
      trough concentrations exceeded the anticipated EC(50) (50 ng/mL) in 10/12
      subjects, persisting for at least 6 hours after the final dose in 4/6 subjects.
      Once-daily SQV/rtv in methadone-maintained subjects is safe and not associated
      with any clinically significant interaction with methadone during 14 days of
      concomitant administration.

PMID- 14973307
TI  - Pharmacokinetics and safety of Fosfluconazole after single intravenous bolus
      injection in healthy male Japanese volunteers.
AB  - This was a single blind, placebo-controlled, escalating single-dose, three-period
      crossover study using two subject cohorts to investigate the safety,
      tolerability, and pharmacokinetics in healthy male Japanese subjects after
      intravenous bolus injection of fosfluconazole 50 to 2000 mg, a phosphate prodrug
      of fluconazole (FLCZ). Fosfluconazole was rapidly converted to FLCZ with only
      minor amounts excreted in the urine (less than 4% of the dose). Fosfluconazole
      had a volume of distribution at the higher doses, which was similar to the
      extracellular volume in man (0.2 L/kg) and was eliminated with a terminal half
      life of 1.5 to 2.5 hours. There was apparent dose proportionality in FLCZ
      pharmacokinetics. C(max) and AUC of FLCZ appeared to increase proportionally with
      increasing doses of fosfluconazole. There were no apparent dose-dependent trends
      in t(max), t(1/2), or mean residence time (MRT) of FLCZ. Bolus injection of
      fosfluconazole was well tolerated at doses of up to 2000 mg in healthy Japanese
      subjects.

PMID- 14973308
TI  - Single oral dose safety, tolerability, and pharmacokinetics of PNU-96391 in
      healthy volunteers.
AB  - The safety, tolerability, and pharmacokinetics of PNU-96391, an orally active
      weak dopamine D2 receptor antagonist with modulatory properties of central
      dopaminergic function, was characterized. Fifty-three healthy normal volunteers
      were enrolled in this randomized, double-blinded, placebo-controlled, single-dose
      study. Subjects were assigned to single oral doses of placebo and 1, 3, 10, 30,
      100, 150, and 200 mg PNU-96391. Safety and tolerability were assessed using
      telemetry, Holter monitoring, surface ECG, vital signs, safety laboratories, and
      adverse event reports. Pharmacokinetic parameters were determined by model
      independent techniques. Adverse events were infrequent, of mild to moderate
      intensity, and in the dose range of 1 to 150 mg. Dose escalation was stopped at
      200 mg because of severe nausea, dizziness, lightheadedness, and tachycardia.
      Besides the increase in heart rate, no other drug-related effects on vital signs
      were observed. Safety laboratory measurements were not significantly changed.
      Evidence of drug activity was demonstrated by a dose-dependent elevation in serum
      prolactin. PNU-96391 was rapidly absorbed, with maximum concentrations achieved
      between 0.5 and 4 hours in all subjects. The half-life of the drug was short (2
      to 6 h). The main metabolite, PNU-100014, was rapidly formed, with a t(max)
      ranging from 1 to 6 hours. Peak levels of the metabolite are approximately half
      of the parent drug, and the half-life is slightly longer (4 to 10 h). Increases
      in dose resulted in linear increases in exposure for both PNU-96391 and PNU
      100014. Hence, PNU-96391 was well tolerated at doses ranging from 1 to 150 mg.

PMID- 14973309
TI  - Pharmacokinetics and safety of viramidine, a prodrug of ribavirin, in healthy
      volunteers.
AB  - Ribavirin, part of the current first-line combination therapy for the treatment
      of chronic hepatitis C, has side effects-in particular, hemolytic anemia-that is
      frequently dose limiting. Based on animal studies, viramidine, a prodrug of
      ribavirin, is converted to ribavirin in the liver. Viramidine dosing yielded 50%
      higher ribavirin levels in the monkey liver but only half in plasma and red blood
      cells compared to ribavirin dosing. At the same dose, it also had a safer profile
      than ribavirin in a 28-day toxicity study in monkeys. The current study was
      carried out to evaluate the safety, tolerability, and pharmacokinetics of
      viramidine in healthy male volunteers (n = 8-18 on viramidine vs. 2 on placebo at
      each dose level) after oral dosing of viramidine at 200, 600, and 1200 mg. There
      were no serious adverse events, and most adverse events were mild. The
      percentages of treatment-emergent events judged to be possibly related to the
      study drug were 50% in the 1200-mg group, 26% in the 600-mg group, and none in
      the 200-mg group. Viramidine was orally absorbed and rapidly converted to
      ribavirin with a t(max) of 1.5 to 3.0 hours for both viramidine and ribavirin in
      plasma. There was dose proportionality in plasma AUC(0-168 h) and C(max) for
      viramidine and in plasma AUC(0-168 h) for ribavirin. Plasma AUC(0-168 h) for
      ribavirin was two to four times higher than plasma AUC(0-168 h) for viramidine,
      indicating that viramidine is extensively metabolized to ribavirin and is a
      prodrug of ribavirin in man. Amounts of viramidine and ribavirin excreted in the
      urine were small (2%-5% of dose), indicating that the main route of elimination
      for both viramidine and ribavirin is metabolism. Both viramidine and ribavirin
      were excreted into urine through the mechanism of glomerular filtration. In
      addition, an evaluation of the effect of a high-fat meal on the pharmacokinetics
      of viramidine and ribavirin after oral dosing of viramidine at 600 mg was
      conducted in healthy male volunteers (n = 33-34) in a crossover study design. A
      high-fat meal increased viramidine plasma AUC(0-168 h) by 44% and C(max) by 20%.
      It also increased ribavirin plasma AUC(0-168 h) by 19% and C(max) by 43%. The
      clinical relevance of these increases is unknown.

PMID- 14973310
TI  - Modulation of sympathetic and somatomotor function by the ventromedial medulla.
AB  - The ventromedial medulla is implicated in a variety of functions including
      nociceptive and cardiovascular modulation and the control of thermoregulation. To
      determine whether single microinjections into the ventromedial medulla elicit
      changes in one or multiple functional systems, the GABA(A) receptor antagonist
      bicuculline was microinjected (70 nl, 5-50 ng) into the ventromedial medulla of
      lightly anesthetized rats, and cardiovascular, respiratory, and nociceptive
      measures were recorded. Bicuculline microinjection into either the midline raphe
      or the laterally adjacent reticular nucleus simultaneously increased
      interscapular brown adipose tissue temperature, heart rate, blood pressure,
      expired [CO(2)], and respiration rate and elicited shivering. Bicuculline
      microinjection also decreased the noxious stimulus-evoked changes in heart rate
      and blood pressure, decreased the frequency of heat-evoked sighs, and suppressed
      the cortical desynchronization evoked by noxious stimulation. Although
      bicuculline suppressed the motor withdrawal evoked by noxious tail heat, it
      enhanced the motor withdrawal evoked by noxious paw heat, evidence for
      specifically patterned nociceptive modulation. Saline microinjections into
      midline or lateral sites had no effect on any measured variable. All bicuculline
      microinjections, midline or lateral, evoked the same set of physiological
      effects, consistent with the lack of a topographical organization within the
      ventromedial medulla. Furthermore, as predicted by the isodendritic morphology of
      cells in the ventromedial medulla, midline bicuculline microinjection increased
      the number of c-fos immunoreactive cells in both midline raphe and lateral
      reticular nuclei. In summary, 70-nl microinjections into ventromedial medulla
      activate cells in multiple nuclei and elicit increases in sympathetic and
      somatomotor tone and a novel pattern of nociceptive modulation.

PMID- 14973311
TI  - GABAB receptor modulation of rapid inhibitory and excitatory neurotransmission
      from subfornical organ and other afferents to median preoptic nucleus neurons.
AB  - Cardiovascular and behavioral responses to circulating angiotensin require intact
      connectivity along the upper lamina terminalis joining the subfornical organ
      (SFO) with the median preoptic nucleus (MnPO). Whole cell patch-clamp recordings
      in sagittal rat brain slice preparations revealed that 28/40 MnPO neurons
      responded to electrical stimulation of SFO efferents with bicuculline-sensitive
      GABA(A) receptor-mediated inhibition and glutamate-mediated postsynaptic
      excitation involving AMPA and N-methyl-d-aspartate (NMDA) receptor subtypes,
      blockable with 2,3-dioxo-6nitro-1, 2,3,4-tetrahydrobenzo [f] quinoxaline-7
      sulfoamide disodium (NBQX) and d-2-amino-4-phosphonovaleric acid (d-APV),
      respectively. Bath applications of baclofen induced a concentration-dependent
      (0.3-10 microM) reduction in these SFO-evoked postsynaptic currents, attenuation
      of SFO-evoked paired-pulse depression, and reduction in frequency (but not
      amplitude) of miniature postsynaptic currents, consistent with an action at
      presynaptic GABA(B) receptors. Baclofen's effects on miniature currents lacked
      sensitivity to barium, omega-conotoxin GVIA, and cadmium. Acting at postsynaptic
      GABA(B) receptors, baclofen hyperpolarized a majority of MnPO neurons by
      increasing a G protein-coupled inwardly rectifying potassium conductance and
      suppressing an N-type high-voltage-activated calcium conductance. The latter
      contributed to reduction in action potential afterhyperpolarization and enhanced
      cell firing and spike frequency adaptation when tested with a depolarizing
      stimulus. All baclofen-induced effects were blockable with CGP52432. CGP52432
      alone had no significant effect on SFO-evoked postsynaptic current amplitudes or
      paired-pulse ratios, but did induce an increase in miniature inhibitory
      postsynaptic current (mIPSC) frequency in 2/4 cells tested, indicating that
      ambient levels of GABA could activate presynaptic GABA(B) receptors on undefined
      inputs. These observations indicate that MnPO neurons receive both a GABAergic
      and glutamatergic innervation from SFO. Both forms of rapid neurotransmission are
      subject to modulation via pre- and postsynaptic GABA(B) receptors.

PMID- 14973312
TI  - Perception of visual space at the time of pro- and anti-saccades.
AB  - The localization of peri-saccadically flashed objects shows two types of errors:
      first, a uniform shift in saccade direction, and second, a compression of visual
      space around the saccade target. Whereas the uniform shift occurs when the
      experiment is performed in complete darkness compression occurs when additional
      visual references are available. Thus peri-saccadic mislocalization contains
      motor and visual components. To distinguish between both factors we compared peri
      saccadic localization errors during pro- and anti-saccades. In the case of anti
      saccades, the visual cue that elicits the saccade and the actual eye movement are
      in opposite directions. We asked whether peri-saccadic compression can be
      observed with anti-saccades, and if so, whether the compression is directed
      toward the visual cue or follows the actual eye movement. In blocked trials,
      subjects performed saccades either toward a visual cue (pro-saccade) or to the
      mirrored position opposite to a visual cue (anti-saccade). Peri-saccadically, we
      flashed a thin vertical bar at one of four possible locations. Subjects had to
      indicate the perceived position of the bar with a mouse pointer about 500 ms
      after the saccade. Experiments were performed in complete darkness and with
      visual references. Peri-saccadic mislocalizations occurred during anti-saccades.
      The mislocalizations were very similar for pro- and anti-saccades in magnitude
      and direction. For both, pro- and anti-saccades, mislocalizations were directed
      toward the actual eye movement and not the visual cue.

PMID- 14973313
TI  - Amplitude and direction of saccadic eye movements depend on the synchronicity of
      collicular population activity.
AB  - Synchronization of neuronal discharges has been observed in numerous brain
      structures, but opinions diverge regarding its significance in neuronal
      processing. Here we investigate whether the motion vectors of saccadic eye
      movements evoked by electrical multisite stimulation of the cat superior
      colliculus (SC) are influenced by varying the degree of synchrony between the
      stimulus trains. With synchronous activation of SC sites, the vectors of the
      resulting saccades correspond approximately to the averages of the vectors of
      saccades evoked from each site alone. In contrast, when the pulses of trains
      applied to the different sites are temporally offset by as little as 5-10 ms, the
      vectors of the resulting saccades come close to the sum of the individual
      vectors. Thus saccade vectors depend not only on the site and amplitude of
      collicular activation but also on the precise temporal relations among the
      respective spike trains. These data indicate that networks within or downstream
      from the SC discriminate with high temporal resolution between synchronous and
      asynchronous population responses. This supports the hypothesis that information
      is encoded not only in the rate of neuronal responses but also in the precise
      temporal relations between discharges.

PMID- 14973314
TI  - Development of intrinsic properties and excitability of layer 2/3 pyramidal
      neurons during a critical period for sensory maps in rat barrel cortex.
AB  - The development of layer 2/3 sensory maps in rat barrel cortex (BC) is experience
      dependent with a critical period around postnatal days (PND) 10-14. The role of
      intrinsic response properties of neurons in this plasticity has not been
      investigated. Here we characterize the development of BC layer 2/3 intrinsic
      responses to identify possible sites of plasticity. Whole cell recordings were
      performed on pyramidal cells in acute BC slices from control and deprived rats,
      over ages spanning the critical period (PND 12, 14, and 17). Vibrissa trimming
      began at PND 9. Spiking behavior changed from phasic (more spike frequency
      adaptation) to regular (less adaptation) with age, such that the number of action
      potentials per stimulus increased. Changes in spiking properties were related to
      the strength of a slow Ca(2+)-dependent afterhyperpolarization. Maturation of the
      spiking properties of layer 2/3 pyramidal neurons coincided with the close of the
      critical period and was delayed by deprivation. Other measures of excitability,
      including I-f curves and passive membrane properties, were affected by
      development but unaffected by whisker deprivation.

PMID- 14973315
TI  - Substrates for coincidence detection and calcium signaling for induction of
      synaptic potentiation in the neonatal visual cortex.
AB  - Regulation of the efficacy of synaptic transmission by activity-dependent
      processes has been implicated in learning and memory as well as in developmental
      processes. We previously described transient potentiation of excitatory synapses
      onto layer 2/3 pyramidal neurons in the visual cortex that is induced by
      coincident presynaptic stimulation and postsynaptic depolarization. In the adult
      visual cortex, activation of N-methyl-d-aspartate (NMDA) glutamate receptors is
      necessary to induce this plasticity. These receptors act as coincidence
      detectors, sensing presynaptic glutamate release and postsynaptic depolarization,
      and cause an influx of Ca(2+) that is necessary for the potentiation. In the
      neurons of the neonatal visual cortex, on the other hand, coincident presynaptic
      stimulation and postsynaptic depolarization induce stable long-term potentiation
      (LTP). In addition, reduced but significant LTP can be induced in many neurons in
      the presence of the NMDA receptor (NMDAR) antagonist, 2-amino-5-phosphonovaleric
      acid despite the Ca(2+) requirement. Therefore there must be an alternative
      postsynaptic Ca(2+) source and coincidence detection mechanism linked to the LTP
      induction mechanism in the neonatal cortex operating in addition to NMDARs. In
      this study, we find that in layer 2/3 pyramidal neurons, release of Ca(2+) from
      inositol trisphosphate (InsP(3)) receptor-mediated intracellular stores and
      influx through voltage-gated Ca(2+) channels (VGCCs) provide alternative
      postsynaptic Ca(2+) sources. We hypothesize that InsP(3)Rs are coincidence
      detectors, sensing presynaptic glutamate release through linkage with group I
      metabotropic glutamate receptors (mGluRs), and depolarization, through VGCCs. We
      also find that the downstream protein kinases, PKA and PKC, have a role in
      potentiation in layer 2/3 pyramidal neurons of the neonatal visual cortex.

PMID- 14973316
TI  - Circadian rhythm in inhibitory synaptic transmission in the mouse suprachiasmatic
      nucleus.
AB  - It is widely accepted that most suprachiasmatic nucleus (SCN) neurons express the
      neurotransmitter GABA and are likely to use this neurotransmitter to regulate
      excitability within the SCN. To evaluate the possibility that inhibitory synaptic
      transmission varies with a circadian rhythm within the mouse SCN, we used whole
      cell patch-clamp recording in an acute brain slice preparation to record GABA
      mediated spontaneous inhibitory postsynaptic currents (sIPSCs). We found that the
      sIPSC frequency in the dorsal SCN (dSCN) exhibited a TTX-sensitive daily rhythm
      that peaked during the late day and early night in mice held in a light:dark
      cycle. We next evaluated whether vasoactive intestinal peptide (VIP) was
      responsible for the observed rhythm in IPSC frequency. Pretreatment of SCN slices
      with VPAC(1)/VPAC(2)- or VPAC(2)-specific receptor antagonists prevented the
      increase in sIPSC frequency in the dSCN. The rhythm in sIPSC frequency was absent
      in VIP/peptide histidine isoleucine (PHI)-deficient mice. Finally, we were able
      to detect a rhythm in the frequency of inhibitory synaptic transmission in mice
      held in constant darkness that was also dependent on VIP and the VPAC(2)
      receptor. Overall, these data demonstrate that there is a circadian rhythm in
      GABAergic transmission in the dorsal region of the mouse SCN and that the VIP is
      required for expression of this rhythm.

PMID- 14973317
TI  - Long-term potentiation of intrinsic excitability in LV visual cortical neurons.
AB  - Neuronal excitability has a large impact on network behavior, and plasticity in
      intrinsic excitability could serve as an important information storage mechanism.
      Here we ask whether postsynaptic excitability of layer V pyramidal neurons from
      primary visual cortex can be rapidly regulated by activity. Whole cell current
      clamp recordings were obtained from visual cortical slices, and intrinsic
      excitability was measured by recording the firing response to small depolarizing
      test pulses. Inducing neurons to fire at high-frequency (30-40 Hz) in bursts for
      5 min in the presence of synaptic blockers increased the firing rate evoked by
      the test pulse. This long-term potentiation of intrinsic excitability (LTP-IE)
      lasted for as long as we held the recording (>60 min). LTP-IE was accompanied by
      a leftward shift in the entire frequency versus current (F-I) curve and a
      decrease in threshold current and voltage. Passive neuronal properties were
      unaffected by the induction protocol, indicating that LTP-IE occurred through
      modification in voltage-gated conductances. Reducing extracellular calcium during
      the induction protocol, or buffering intracellular calcium with bis-(o
      aminophenoxy)-N,N,N',N'-tetraacetic acid, prevented LTP-IE. Finally, blocking
      protein kinase A (PKA) activation prevented, whereas pharmacological activation
      of PKA both mimicked and occluded, LTP-IE. This suggests that LTP-IE occurs
      through postsynaptic calcium influx and subsequent activation of PKA. Activity
      dependent plasticity in intrinsic excitability could greatly expand the
      computational power of individual neurons.

PMID- 14973318
TI  - Inhibition of visual discrimination during a memory-guided saccade task.
AB  - Voluntary behavior critically depends on attentional selection and short-term
      maintenance of perceptual information. Recent research suggests a tight coupling
      of both cognitive functions with visual processing being selectively enhanced by
      working memory representations. Here, we combined a memory-guided saccade
      paradigm (6-s delay) with a visual discrimination task, performed either 1,500,
      2,500, or 3,500 ms after presentation of the memory cue. Contrary to what can be
      expected from previous studies, our results show that memory of spatial cues can
      transiently delay speeded discrimination of stimuli presented at remembered
      locations. This effect was not observed in a control experiment without memory
      requirements. Furthermore, delayed discrimination was dependent on the strength
      of actual memory representations as reflected by accuracy of memory-guided
      saccades. We propose an active inhibitory mechanism that counteracts facilitating
      effects of spatial working memory, promoting flexible orienting to novel
      information during maintenance of spatial memoranda for intended actions.
      Inhibitory delay-period activity in prefrontal cortex is a likely source for this
      mechanism which may be mediated by prefronto-tectal projections.

PMID- 14973319
TI  - Rat cutaneous RA afferents activated by two-dimensional skin stretch.
AB  - Skin develops biaxial stresses and strains when stretched. Rapidly adapting
      cutaneous mechanoreceptor neurons are known to be stretch sensitive, yet in the
      past, they have been studied using stretch stimuli applied along only a single
      direction. In this study, cutaneous rapidly adapting mechanoreceptors were
      studied in preparations of isolated skin in which the skin was stretched
      dynamically using biaxial stretch stimuli and in which loads and displacements
      were measured along two directions. Stretch stimuli followed a pseudo-Gaussian
      waveform and were applied along either one or two directions simultaneously.
      Associations between spikes and mechanical variables were determined using
      multiple logistic regression. When the skin was actuated along a single
      direction, holding the orthogonal axis fixed, spike responses were strongly
      associated with mechanical variables along the actuated direction. The variables
      were stress and its rate of change, the rate of change of strain, and the product
      of stress and its rate of change, which is proportional to strain energy density.
      When the skin was stretched along a single direction, spikes were very poorly
      associated with stress variables measured along the direction orthogonal to the
      stretch. Afferents showed weak directional selectivity: they were slightly more
      responsive to the variable stress along the circumferential direction of the
      hindlimb. When the skin was stretched biaxially (i.e., along both directions
      simultaneously) with identical pseudo-Gaussian noise stimuli, neuronal responses
      were associated with the same variables as above, but the associations were
      weaker.

PMID- 14973320
TI  - Push-pull mechanism of selective attention in human extrastriate cortex.
AB  - Selective attention operates in visual cortex by facilitating processing of
      selected stimuli and by filtering out unwanted information from nearby
      distracters over circumscribed regions of visual space. The neural representation
      of unattended stimuli outside this focus of attention is less well understood. We
      studied the neural fate of unattended stimuli using functional magnetic resonance
      imaging by dissociating the activity evoked by attended (target) stimuli
      presented to the periphery of a visual hemifield and unattended (distracter)
      stimuli presented simultaneously to a corresponding location of the contralateral
      hemifield. Subjects covertly directed attention to a series of target stimuli and
      performed either a low or a high attentional-load search task on a stream of
      otherwise identical stimuli. With this task, target-search-related activity
      increased with increasing attentional load, whereas distracter-related activity
      decreased with increasing load in areas V4 and TEO but not in early areas V1 and
      V2. This finding presents evidence for a load-dependent push-pull mechanism of
      selective attention that operates over large portions of the visual field at
      intermediate processing stages. This mechanism appeared to be controlled by a
      distributed frontoparietal network of brain areas that reflected processes
      related to target selection during spatially directed attention.

PMID- 14973321
TI  - Muscular and postural synergies of the human hand.
AB  - Because humans have limited ability to independently control the many joints of
      the hand, a wide variety of hand shapes can be characterized as a weighted
      combination of just two or three main patterns of covariation in joint rotations,
      or "postural synergies." The present study sought to align muscle synergies with
      these main postural synergies and to describe the form of membership of motor
      units in these postural/muscle synergies. Seventeen joint angles and the
      electromyographic (EMG) activities of several hand muscles (both intrinsic and
      extrinsic muscles) were recorded while human subjects held the hand statically in
      52 specific shapes (i.e., shaping the hand around 26 commonly grasped objects or
      forming the 26 letter shapes of a manual alphabet). Principal-components analysis
      revealed several patterns of muscle synergy, some of which represented either
      coactivation of all hand muscles, or reciprocal patterns of activity (above and
      below average levels) in the intrinsic index finger and thumb muscles or (to a
      lesser extent) in the extrinsic four-tendoned extensor and flexor muscles. Single
      and multiunit activity was generally a multimodal function of whole hand shape.
      This implies that motor-unit activation does not align with a single synergy;
      instead, motor units participate in multiple muscle synergies. Thus it appears
      that the organization of the global pattern of hand muscle activation is highly
      distributed. This organization mirrors the highly fractured somatotopy of
      cortical hand representations and may provide an ideal substrate for motor
      learning and recovery from injury.

PMID- 14973322
TI  - Information transfer rate of nonspiking afferent neurons in the crab.
AB  - The thoracic-coxal muscle receptor organ (TCMRO) is the only proprioceptor at the
      thoracic-coxal joint in the crab leg. The S and T afferent neurons of the TCMRO
      convey signals to the CNS solely by means of graded changes in membrane
      potential. The rate of information transfer of these afferents was determined by
      measuring the signal-to-noise ratio (SNuR) of these cells after repeated
      stimulation of the receptor with identical sequences of random movement and
      applying the Shannon formula for the information capacity of a Gaussian channel.
      Intracellular recordings were made from the S and T afferents adjacent to the
      transduction site at the origin of the receptor and along the axon 5-7 mm distal
      to this site. These nonspiking afferents transduce receptor movement and transmit
      this information with extremely high fidelity. The SNR of both neurons near the
      transduction site was >1000 over most of the 200 Hz stimulation bandwidth, and
      the mean information transfer rate was approximately 2,500 bits/s. When
      calculated over a wider bandwidth of 500 Hz, the information rate was >4,600
      bits/s. The effect of axonal cable properties on the information rate was
      evaluated by determining the SNR from membrane potential recordings made 5-7 mm
      distal to the transduction region. The major effect of graded transmission along
      the axon was attenuation and low-pass filtering of the sensory signal. The
      consequent reduction in signal power and bandwidth decreased the information
      transfer by approximately 10-15% over 200 Hz and approximately 30% over a 500 Hz
      bandwidth.

PMID- 14973323
TI  - Centrifugal inputs modulate taste aversion learning associated parabrachial
      neuronal activities.
AB  - Our previous studies have demonstrated that gustatory neurons in the parabrachial
      nucleus (PBN) show altered responses after the acquisition of conditioned taste
      aversion (CTA) to NaCl. The present study was conducted 1) to examine centrifugal
      influences on the altered gustatory activity of CTA-trained rats, and 2) to
      evaluate the role of amiloride-sensitive (ASN) and -insensitive NaCl (AIN) best
      units in coding the taste of NaCl. Animals were separated into 2 groups: a CTA
      group that had acquired taste aversion to 0.1 M NaCl and a control group that
      underwent pseudoconditioning before the recording experiment. Single-neuron
      activity, in 2 separate series of experiments, was extracellularly recorded in
      anesthetized rats. In the stimulation studies, the effects of electrical
      stimulation of the gustatory cortex (GC) or the central nucleus of amygdala (CeA)
      were examined on firing of PBN taste units. CeA stimulation produced excitatory
      effect in significantly more neurons in the CTA group (n = 8) than in the control
      group (n = 1). Furthermore, ASN-best units in the CTA group showed larger
      responses to NaCl than similar units in the control group. In the decerebration
      experiment, there was no statistical difference among the taste responses between
      the 2 groups in any best-stimulus category. These results suggest that CTA
      conditioning uses an effective central amygdaloid input to modulate activity of
      gustatory neurons in the PBN. Data also substantiate that amiloride-sensitive
      components of NaCl-best neurons play a critical role in the recognition of
      distinctive taste of NaCl.

PMID- 14973324
TI  - Flexible control of flexible objects. Focus on "An experimentally confirmed
      mathematical model for human control of a non-rigid object".

PMID- 14973325
TI  - Coupling between feline cerebellum (fastigial neurons) and motoneurons
      innervating hindlimb muscles.
AB  - The aims of the study were twofold: (1) to verify the hypothesis that neurons in
      the fastigial nucleus excite and inhibit hindlimb alpha-motoneurons and (2) to
      determine both the supraspinal and spinal relays of these actions. Axons of
      fastigial neurons were stimulated at the level of their decussation in the
      cerebellum, within the hook bundle of Russell, in deeply anesthetized cats with
      only the right side of the spinal cord intact. The resulting excitatory
      postsynaptic potentials and inhibitory postsynaptic potentials were analyzed in
      motoneurons on the left side of the lumbar enlargement. Postsynaptic potentials
      evoked by the first effective stimulus were induced at latencies <2 ms from
      descending volleys and <1 ms from interneuronally relayed volleys, indicating a
      trisynaptic coupling between the fastigial neurons and alpha-motoneurons, via
      commissural interneurons on the right side. Cerebellar stimulation facilitated
      the synaptic actions of both vestibulospinal and reticulospinal tract fibers.
      However, the study leads to the conclusion that trisynaptic fastigial actions are
      mediated via vestibulospinal rather than reticulospinal tract fibers [stimulated
      within the lateral vestibular nucleus (LVN) and the medial longitudinal fascicle
      (MLF), respectively]. This is indicated firstly by collision between descending
      volleys induced by cerebellar stimulation and volleys evoked by LVN stimuli but
      not by MLF stimuli. Second, similar cerebellar actions were evoked before and
      after a transection of MLF. Mutual facilitation between the fastigial and
      reticulospinal, as well as between the fastigial and vestibulospinal actions,
      could be due to the previously reported integration of descending vestibulospinal
      and reticulospinal commands by spinal commissural interneurons.

PMID- 14973326
TI  - Enhancement of potency and efficacy of NADA by PKC-mediated phosphorylation of
      vanilloid receptor.
AB  - The search for an endogenous ligand for the vanilloid receptor (VR or TRPV1) has
      led to the identification of N-arachidonyl dopamine (NADA). This study
      investigates the role of protein kinase C (PKC)-mediated phosphorylation on NADA
      induced membrane currents in Xenopus oocytes heterologously expressing TRPV1 and
      in dorsal root ganglion (DRG) neurons. In basal state, current induced by 10
      microM NADA is 5-10% of the current induced by 1 microM capsaicin or protons at
      pH 5. However, PKC activator, phorbol 12,13-dibutyrate (PDBu) strongly
      potentiated ( approximately 15-fold) the NADA-induced current. Repeated
      application of NADA at short intervals potentiated its own response approximately
      fivefold in a PKC-dependent manner. PKC inhibitor, bisindolylmaleimide (BIM, 500
      nM), a mutant TRPV1 (S800A/S502A), and maximal activation of PKC abolished the
      potentiation induced by repeated application of NADA. As a further confirmation
      that NADA could stimulate PKC, pretreatment with NADA potentiated the response of
      protons at pH 5 (approximately 20 fold), which was dramatically reduced in the
      mutant TRPV1. In DRG neurons, capsaicin (100 nM) induced a approximately 15 mV
      depolarization and initiated a train of action potentials compared with 1 microM
      NADA that produced a approximately 5 mV response. Pretreatment with PDBu induced
      significantly larger depolarization and potentiated NADA-induced current.
      Furthermore, exposure of NADA to the intracellular surface of the membrane
      induced larger currents suggesting inaccessibility to the intracellular binding
      site might contribute to its weaker action. These results indicate that NADA is a
      potent agonist of VR when the receptor is in the PKC-mediated phosphorylation
      state.

PMID- 14973327
TI  - Large-scale determination of the methylation status of retrotransposons in
      different tissues using a methylation tags approach.
AB  - A technique for simultaneous determination of the methylation status of numerous
      loci containing retroelements (REs) is reported. It is based on the observation
      that methylated and unmethylated areas in the genome are usually extended, and
      therefore the methylation of particular methyl-sensitive restriction endonuclease
      recognition sites might reflect the methylation status of DNA regions around
      them. The method includes dot-blot hybridization of repeat flanking sequences
      arrayed on a solid support with specifically amplified flanking regions of
      presumably unmethylated repeats. A multitude of flanking regions of REs adjacent
      to unmethylated restriction sites are amplified simultaneously, providing a
      complex hybridization probe. The technique thus allows the determination of the
      methylation status of restriction sites, which serve as tags of the methylation
      status of the surrounding regions. The validity of the technique was confirmed by
      various means, including bisulfite sequencing. The technique was successfully
      applied to the identification of methylation patterns of the regions surrounding
      38 human-specific HERV-K(HML-2) long terminal repeats in cerebellum- and lymph
      node-derived genomic DNAs. The described technique can be readily adapted to the
      use of DNA microarray technology.

PMID- 14973328
TI  - Strong positional preference in the interaction of LNA oligonucleotides with DNA
      polymerase and proofreading exonuclease activities: implications for genotyping
      assays.
AB  - The effect of locked nucleic acid (LNA) modification position upon representative
      DNA polymerase and exonuclease activities has been examined for potential use in
      primer extension genotyping applications. For the 3'-->5' exonuclease activities
      of four proofreading DNA polymerases (Vent, Pfu, Klenow fragment and T7 DNA
      polymerase) as well as exonuclease III, an LNA at the terminal (L-1) position of
      a primer is found to provide partial protection against the exonucleases of the
      two family B polymerases only. In contrast, an LNA residue at the penultimate (L
      2) position generates essentially complete nuclease resistance. The polymerase
      active sites of these enzymes also display a distinct preference. An L-1 LNA
      modification has modest effects upon poly merization, but an L-2 LNA group slows
      dTTP incorporation somewhat while virtually abolishing extension with ddTTP or
      acyTTP terminators, even with A488L Vent DNA polymerase engineered for terminator
      incorporation. These observations on active site preference have been utilized to
      demonstrate two novel assays: exonuclease-mediated single base extension (E-SBE)
      and proofreading allele-specific extension (PRASE). We show that a model PRASE
      genotyping reaction with L-2 LNA primers offers greater specificity than existing
      non-proofreading assays, whether or not the non-proofreading reaction employs LNA
      modified primers.

PMID- 14973329
TI  - Surfection: a new platform for transfected cell arrays.
AB  - Efficient high-throughput expression of genes in mammalian cells can facilitate
      large-scale functional genomic studies. Towards this aim, we developed a simple
      yet powerful method to deliver genes into cells by cationic polymers on the
      surface of substrates. Transfection can be achieved by directly contacting
      nucleic acid-cell mixtures with the cationic substrates, e.g.
      polyethylenimine/collagen-coated wells. This single-step matrix-surface- mediated
      transfection method, termed 'surfection', can efficiently deliver multiple
      plasmids into cells and can successfully assay siRNA-mediated gene silencing.
      This technology represents the easiest method to transfer combinations of genes
      in large-scale arrays, and is a versatile tool for live-cell imaging and cell
      based drug screening.

PMID- 14973330
TI  - Unlocking hidden genomic sequence.
AB  - Despite the success of conventional Sanger sequencing, significant regions of
      many genomes still present major obstacles to sequencing. Here we propose a novel
      approach with the potential to alleviate a wide range of sequencing difficulties.
      The technique involves extracting target DNA sequence from variants generated by
      introduction of random mutations. The introduction of mutations does not destroy
      original sequence information, but distributes it amongst multiple variants. Some
      of these variants lack problematic features of the target and are more amenable
      to conventional sequencing. The technique has been successfully demonstrated with
      mutation levels up to an average 18% base substitution and has been used to read
      previously intractable poly(A), AT-rich and GC-rich motifs.

PMID- 14973332
TI  - A simple method for estimating global DNA methylation using bisulfite PCR of
      repetitive DNA elements.
AB  - We report a method for studying global DNA methylation based on using bisulfite
      treatment of DNA and simultaneous PCR of multiple DNA repetitive elements, such
      as Alu elements and long interspersed nucleotide elements (LINE). The PCR
      product, which represents a pool of approximately 15 000 genomic loci, could be
      used for direct sequencing, selective restriction digestion or pyrosequencing, in
      order to quantitate DNA methylation. By restriction digestion or pyrosequencing,
      the assay was reproducible with a standard deviation of only 2% between assays.
      Using this method we found that almost two-thirds of the CpG methylation sites in
      Alu elements are mutated, but of the remaining methylation target sites, 87% were
      methylated. Due to the heavy methylation of repetitive elements, this assay was
      especially useful in detecting decreases in DNA methylation, and this assay was
      validated by examining cell lines treated with the methylation inhibitor 5-aza
      2'deoxycytidine (DAC), where we found a 1-16% decrease in Alu element and 18-60%
      LINE methylation within 3 days of treatment. This method can be used as a
      surrogate marker of genome-wide methylation changes. In addition, it is less
      labor intensive and requires less DNA than previous methods of assessing global
      DNA methylation.

PMID- 14973333
TI  - Generating in vitro transcripts with homogenous 3' ends using trans-acting
      antigenomic delta ribozyme.
AB  - In most in vitro run-off transcription reactions with T7 RNA polymerase,
      transcripts with heterogeneous ends are commonly obtained. Towards the goal of
      finding a simple and effective procedure for correct processing of their 3' ends
      we propose the use of trans-acting antigenomic delta ribozyme. We demonstrate
      that the extension of nascent transcripts with only seven nucleotides
      complementary to the ribozyme's recognition site, and subsequently, the removal
      of those nucleotides with the ribozyme acting in trans, is an efficient procedure
      for generating transcripts with homogenous 3' ends. This approach was tested on
      two model RNA molecules: an in vitro transcript of yeast tRNA(Phe) and a delta
      ribozyme, which processed itself during transcription. The proposed procedure is
      a simple alternative to the use of ribozymes as cis-cleaving autocatalytic
      cassettes attached to transcript 3' ends. As there is little possibility that the
      required additional stretch, only seven nucleotides long, enters into stable
      interactions with other parts of the transcripts, it can be cleaved off with high
      efficacy.

PMID- 14973334
TI  - Motion enslaving among multiple fingers of the human hand.
AB  - The purpose of the current study was to examine motion enslaving characteristics
      of multiple fingers during isolated flexion of the distal interphalangeal joints.
      Because the distal interphalangeal joints are flexed by multiple tendons of the
      single flexor digitorum profundus, the current experimental design provided a
      unique advantage to understand inter-finger enslaving effects due to the flexor
      digitorum profundus. Eight subjects were instructed to flex the distal
      interphalangeal joint of each individual finger from the fully extended position
      to the fully flexed position as quickly as possible. Maximal angular
      displacements, velocities, or accelerations of individual fingers were used to
      calculate the enslaving effects. An independence index, defined as the ratio of
      the maximal displacement of a master finger to the sum of the maximal
      displacements of the master and slave fingers, was used to quantify relative
      independence of each finger. The angular displacements of the index, middle,
      ring, and little fingers were 68.6(degrees) (+/-7.7), 68.1(degrees) (+/-10.1),
      68.1(degrees) (+/-9.7), and 74.7(degrees) (+/-13.3), respectively. The motion of
      a master finger was invariably accompanied by motion of 1 or 2 slave fingers.
      Angular displacements of master and slave fingers increased to maximum values
      with time monotonically. Velocity curves demonstrated bell-shaped profile, and
      the acceleration curves were sinusoidal. Enslaving effects were generated mainly
      on the neighboring fingers. The amount of enslaving on the middle and ring
      fingers exceeded more than 60% of their own maximum angular displacements when a
      single adjacent finger moved. The index finger had the highest level of
      independence as indicated by the lowest enslaving effects on other fingers or by
      other fingers. The independence indices of the index, middle, ring, and little
      fingers were 0.812 (+/-0.070), 0.530 (+/-0.051), 0.479 (+/-0.099), and 0.606 (+/
      0.148), respectively. In all tasks, motion of slave fingers always lagged with
      respect to the master finger. Time delays, on average, ranged from 7.8 (+/-5.0)
      to 35.9 (+/-22.1) ms. Our results suggest that there exist relatively large
      enslaving effects among the compartments of the flexor digitorum profundus, and
      functional independence of fingers in daily activities is likely enhanced through
      synergistic activities of multiple muscles, including flexors and extensor.

PMID- 14973335
TI  - Pointing to an allocentric and egocentric remembered target.
AB  - Pointing to a visual target that disappears prior to movement requires the
      maintenance of a memory representation about the location of the target. It has
      been shown that a target can be stored egocentrically, allocentrically, or in
      both frames of reference simultaneously. The main goal of the present study was
      to compare the accuracy and kinematics of a pointing movement to a remembered
      target when egocentric, allocentric, or combined egocentric and allocentric
      coding was possible. The task was to localize, memorize, and reach to a
      remembered target. Condition 1 was the "no-context" condition and involved
      presenting the target in a completely dark environment (egocentric condition).
      For 2 other conditions, the target was presented within a visual context provided
      by an illuminated square. Condition 2 was the "stationary-context" condition and
      involved keeping the context at the same position during the whole trial
      (egocentric and/or allocentric coding). Condition 3 was a "moved-context"
      condition that involved shifting the context to a different location during the
      recall delay (allocentric coding). Movement accuracy and kinematics results were
      strikingly similar for the moved-context and stationary-context conditions. These
      results suggest that when both allocentric and egocentric coding are possible, an
      allocentric strategy is used.

PMID- 14973336
TI  - Bimanual directional interference: the effect of normal versus augmented visual
      information feedback on learning and transfer.
AB  - When performing movements with different spatial trajectories in both upper limbs
      simultaneously, patterns of interference emerge that can be overcome with
      practice. Even though studies on the role of augmented feedback in motor learning
      have been abundant, it still remains to be discovered how overcoming such
      specific patterns of spatial interference can be optimized by instructional
      intervention. In the present study, one group acquired a bimanual movement with
      normal vision, whereas a second group received augmented feedback of the obtained
      trajectories on a computer screen in real time. Findings revealed that, relative
      to normal vision, the augmented feedback hampered skill learning and transfer to
      different environmental conditions. These observations are discussed in view of
      the benefits and pitfalls of augmented feedback in relation to task context and
      instructional condition.

PMID- 14973331
TI  - Simple cDNA normalization using kamchatka crab duplex-specific nuclease.
AB  - We developed a novel simple cDNA normalization method [termed duplex-specific
      nuclease (DSN) normalization] that may be effectively used for samples enriched
      with full-length cDNA sequences. DSN normalization involves the denaturation
      reassociation of cDNA, degradation of the double-stranded (ds) fraction formed by
      abundant transcripts and PCR amplification of the equalized single-stranded (ss)
      DNA fraction. The key element of this method is the degradation of the ds
      fraction formed during reassociation of cDNA using the kamchatka crab DSN, as
      described recently. This thermostable enzyme displays a strong preference for
      cleaving ds DNA and DNA in DNA-RNA hybrid duplexes compared with ss DNA and RNA,
      irrespective of sequence length. We developed normalization protocols for both
      first-strand cDNA [when poly(A)+ RNA is available] and amplified cDNA (when only
      total RNA can be obtained). Both protocols were evaluated in model experiments
      using human skeletal muscle cDNA. We also employed DSN normalization to normalize
      cDNA from nervous tissues of the marine mollusc Aplysia californica (a popular
      model organism in neuroscience) to illustrate further the efficiency of the
      normalization technique.

PMID- 14973337
TI  - Assessment of postural response after a self-initiated perturbation.
AB  - The aim of this study was to assess postural response efficiency to a self
      initiated perturbation using an original method based on the inverted pendulum
      model. Eight young subjects were asked to perform bilateral arm raising and
      lowering at 3 different speeds while standing on a force plate. The time
      necessary to recover a steady state following the movement was computed by
      analyzing the time evolution of the coefficient of determination between the
      center of pressure and center of mass difference variable (COP-COM) and the
      horizontal acceleration of the COM. Results show a spatial reorganization (hip
      strategy) of the segments following the perturbation and a strong influence of
      the linear relationship to the arm velocity. However, the conditions of arm
      velocity did not have any effect on the time response of the postural control,
      suggesting that this parameter would be an invariant characteristic of the
      movement. These results support the existence of an internal representation of
      the inertial constraints related to the movement execution.

PMID- 14973338
TI  - Roles of motor-unit recruitment in producing force variability of simulated
      muscle contractions.
AB  - The purpose of this study was to examine the effect of motor-unit recruitment on
      force variability by using computer simulated isometric contractions of a hand
      muscle (i.e., first dorsal interosseus). The force was simulated at 10 levels of
      excitation, ranging from 10 to 100% of maximum. Two recruitment conditions were
      simulated to compare the relative effect of motor-unit recruitment (MUR) on the
      relationship of force variability and level of force. One condition (40%MUR)
      recruited all motor units at 40% of the maximum excitation level, and the other
      (50%MUR) recruited all motor units at 50% of the maximum. The 40%MUR condition
      had a greater number of motor units than the 50%MUR group before the excitation
      level reached 50% of the maximum. The results showed that force variability
      increased at a faster rate before the completion of motor-unit recruitment and,
      thereafter, increased at a slower rate. In addition, the 40%MUR group showed
      greater force variability than the 50%MUR group. These data suggest that motor
      unit recruitment is an important factor in causing force variability.

PMID- 14973339
TI  - The control of memory-guided reaching movements in peripersonal space.
AB  - The goal of the present investigation was to explore the putative contributions
      of feedforward- and feedback-based processes in the control of memory-guided
      reaching movements. Participants (N = 4) completed an extensive number of
      reaching movements (2700) to 3 midline targets (20, 30, 40 cm) in 6 visual
      conditions: full-vision, open-loop, and four memory-guided conditions (0, 200,
      400, and 600 ms of delay). To infer limb control, we used a regression technique
      to examine the within-trial correspondence between the spatial position of the
      limb at peak acceleration, peak velocity, peak deceleration, and the ultimate
      movement endpoint. A high degree of within-trial correspondence would suggest
      that the final position of the limb was largely specified prior to movement onset
      and not adjusted during the action (i.e., feedforward control); conversely, a low
      degree of within-trial correspondence would suggest that movements were modified
      during the reaching trajectory (i.e., feedback control). Full-vision reaches were
      found to be more accurate and less variable than open-loop and memory-guided
      reaches. Moreover, full-vision reaches demonstrated only modest within-trial
      correspondence between the spatial position of the limb at each kinematic marker
      and the ultimate movement endpoint, suggesting that reaching accuracy was
      achieved by adjusting the limb trajectory throughout the course of the action.
      Open-loop and memory-guided movements exhibited strong within-trial
      correspondence between final limb position and the position of the limb at peak
      velocity and peak deceleration. This strong correspondence indicates that the
      final position of the limb was largely determined by processes that occurred
      before the reach was initiated; errors in the planning process were not corrected
      during the course of the action. Thus, and contrary to our previous findings in a
      video-based aiming task, it appears that stored target information is not
      extensively (if at all) used to modify the trajectory of reaching movements to
      remembered targets in peripersonal space.

PMID- 14973340
TI  - Preferential cleavage of Paramecium DNA mediated by the C. elegans Tc1
      transposase in vitro.
AB  - In the ciliate Paramecium aurelia complex, thousands of internal eliminated
      sequences (IESs) are excised from the germline micronuclear DNA during
      macronuclear differentiation. Based on the resemblance of Paramecium IES end
      sequences to Tc1 transposon termini, it has been proposed that Paramecium IESs
      might have degenerately evolved from Tc1 family transposons, and still be removed
      by an enzyme homologous to a Tc1 transposase. In this study, we found that
      transposase preferentially cleaved (or nicked) 58 sites near the IESs in
      Paramecium DNA, at sequences consisting of TT or TCTA. Since one excision
      junction of the P. primaurelia W2 IES was included in such sites, this suggests
      that a Tc1-like transposase is involved in the IES excision process, although it
      is probably not a sole factor responsible for the precise cleavage. In addition,
      unmethylated substrate DNA appeared to decrease the cleavage specificity,
      suggesting an involvement of DNA methylation in the cleavage. Although these
      results do not directly address the transposon origin of Paramecium IESs, it is
      likely that the enzymatic machinery responsible for the initial cleavage is
      derived from a Tc1-like transposase. The mechanism necessary for precise excision
      is discussed, in relation to recent knowledge of IES excision obtained in
      Tetrahymena and Paramecium.

PMID- 14973341
TI  - Genetic variation of Avicennia marina (Forsk.) Vierh. (Avicenniaceae) in Vietnam
      revealed by microsatellite and AFLP markers.
AB  - Genetic variation of Avicennia marina in the costal area of Vietnam was examined
      using microsatellite and AFLP markers. By using five microsatellite loci a total
      of 21 alleles were detected. The average number of alleles per locus per
      population ranged from 1.667 to 3.000. The observed heterozygosity varied from
      0.180 to 0.263, with an average of 0.210 indicating relatively low level of
      genetic variation comparing to the previous studies on A. marina in the worldwide
      range. The expected heterozygosity was larger than the observed heterozygosity
      leading to positive inbreeding coefficients in all the six populations. Highly
      significant departures from Hardy-Weinberg Equilibrium were detected in four
      populations. AFLP analysis revealed a total of 386 loci, of which 232 (60.1%)
      were polymorphic. In congruent with microsatellite markers relatively low levels
      of genetic variation were detected at both gene and nucleotide levels (H = 0.086;
      pi = 0.0054). Reduced level of genetic variation was found in the central
      population, and in the southern populations. Both microsatellite and AFLP markers
      revealed large genetic differentiation (F(ST) = 0.262 and 0.338, respectively)
      indicating strong genetic structure among regional populations. Pairwise genetic
      distance by AFLP showed two populations in the north and the other two in the
      south are closely related each other.

PMID- 14973342
TI  - Genomic structure of the NtPDR1 gene, harboring the two miniature inverted-repeat
      transposable elements, NtToya1 and NtStowaway101.
AB  - Here we report the genomic structure including the promoter sequence and coding
      region of NtPDR1 (Nicotiana tabacum Pleiotropic Drug Resistance 1), which is an
      elicitor-responsive gene encoding an ATP binding cassette (ABC) transporter that
      might be involved in the defense response in tobacco, as we reported recently.
      The NtPDR1 gene consists of 20 exons and 19 introns. Among the introns, the first
      and fifth are much larger than the others and harbor typical miniature inverted
      repeat transposable elements (MITEs). One of the MITE elements in the first
      intron, termed NtToya1, belongs to the Toya family that was recently described in
      rice, while the other element in the fifth intron, termed NtStowaway101, shows
      high homology with the Stowaway elements of the IS630-Tc1-mariner family. Many of
      the genes we found to harbor Toya and Stowaway elements in Nicotiana species by
      BLAST search are also involved in stress responses or plant-pathogen
      interactions. The existence of putative cis-elements (a GCC box, three W boxes,
      and several JA-responsive elements) in the promoter region supports our previous
      finding that this gene is strongly inducible by elicitation and methyljasmonate,
      and that this ABC transporter might be essential for plant defense responses.
      Furthermore, Southern blot analysis and PCR amplification of the introns
      harboring the MITE-like elements from genomic DNA of three Nicotiana species
      suggests that NtPDR1 originated from N. sylvestris.

PMID- 14973343
TI  - Molecular phylogenetic analysis of ant subfamily relationship inferred from rDNA
      sequences.
AB  - The relationships among ant subfamilies were studied by phylogenetic analysis of
      rDNA sequences of 15 species from seven subfamilies. PCR primers were designed on
      the basis of the rDNA sequence of the Australian bulldog ant, Myrmecia croslandi,
      previously determined. Phylogenetic trees were constructed using sequences of a
      fragment of 18S rDNA (1.8 kb), a fragment of 28S rDNA (0.7 kb excluding variable
      regions) and a combination of the 18S and 28S rDNAs, by neighbor-joining (NJ),
      maximum parsimony (MP) and maximum likelihood (ML). rDNA sequences corresponding
      to the same fragments from three non-ant hymenopteran species (a sawfly, a bee
      and a wasp) were employed as outgroups. These trees indicated that the ant
      subfamilies were clustered singly, and, among the seven subfamilies examined,
      Ponerinae and six other subfamilies are in a sister-groups relationship. The
      relationship among the six subfamilies, however, was not clarified. The
      phylogenetic trees constructed in the present study are not in contradiction to
      the tree from cladistic analysis of morphological data by Baroni Urbani et al.
      (1992) and the tree from morphological and molecular data (Ward and Brady, 2003),
      but are inconsistent with the traditional phylogeny. The present results thus
      raise a question as to the status of some traditionally employed "key"
      morphological characters. The present results also call for a reexamination of
      Amblyopone traditionally treated as a member of Ponerinae as belonging to a new
      subfamily.

PMID- 14973344
TI  - Evidence for male XO sex-chromosome system in Pentodon bidens punctatum
      (Coleoptera Scarabaeoidea: Scarabaeidae) with X-linked 18S-28S rDNA clusters.
AB  - In scarab beetle species of the genus Pentodon, the lack of analysis of sex
      chromosomes in females along with the poor characterization of sex chromosomes in
      the males, prevented all previous investigations from conclusively stating sex
      determination system. In this study, somatic chromosomes from females and
      spermatogonial chromosomes from males of Pentodon bidens punctatum (Coleoptera:
      Scarabaeoidea: Scarabaeidae) from Sicily have been analyzed using non
      differential Giemsa staining. Two modal numbers of chromosomes were obtained: 2n
      = 20 and 19 in females and males, respectively. This finding along with other
      karyological characteristics such as the occurrence of one unpaired, heterotypic
      chromosome at metaphase-I and two types of metaphase-II spreads in spermatocytes
      demonstrate that a XO male/XX female sex determining mechanism - quite unusual
      among Scarabaeoidea - operates in the species investigated here. Spermatocyte
      chromosomes have also been examined after a number of banding techniques and
      fluorescent in situ hybridization with ribosomal sequences as a probe (rDNA
      FISH). The results obtained showed that silver and CMA(3) staining were
      inadequate to localize the chromosome sites of nucleolus organizer regions (NORs)
      due to the over-all stainability of both constitutive heterochromatin and
      heterochromatin associated to the NORs. This suggests that heterochromatic DNA of
      P. b. punctatum is peculiar as compared with other types of heterochromatin
      studied so far in other invertebrate taxa. By rDNA FISH major ribosomal genes
      were mapped on the X chromosome.

PMID- 14973345
TI  - Early and late angiographic and clinical outcome following helistent stent
      implantation.
AB  - There is still a lack of data on the influence of different stent designs on long
      term restenosis rates and major adverse cardiac events (MACE) with the use of new
      antithrombotic regimens. We evaluated the midterm (6 months) clinical and
      angiographic and lateterm (2 years) clinical outcome of Helistent stent
      implantation. The study population consisted of 150 patients with high risk
      factor rates who had single or multivessel disease and had undergone coronary
      Helistent stent implantation with new antiplatelet regimens. The control coronary
      angiographies were done at 6 months and they were followed clinically to the end
      of 2 years. In 150 patients, 236 Helistent stents were implanted for 224 lesions.
      Helistent stent implantation was associated with a very high success rate (99%).
      The angiographic re-stenosis rate was 11.3% at 6 months. Only 16% of the patients
      experienced target lesion revascularization, 20% of the patients experienced MACE
      and of them, only 3.3% died at the end of two year follow-up period. The results
      demonstrate that the Helistent stent can be implanted with a high success rate
      with encouraging 6 month angiographic and late clinical outcomes.

PMID- 14973346
TI  - Effects of a beta-blocker on ventricular late potentials in patients with acute
      anterior myocardial infarction receiving successful thrombolytic therapy.
AB  - Late potentials (LP) detected on the signal-averaged electrocardiogram (SAECG)
      predict arrhythmic events after acute myocardial infarction (AMI). It is also
      well established that successful thrombolytic therapy reduces the incidence of
      LP. Our aim was to evaluate the effects of a beta-blocker on LP in patients
      receiving thrombolytic therapy. We studied 40 patients presenting with
      anteroseptal AMI (< 6 hours). All patients received thrombolytic therapy and were
      evaluated with coronary angiography at predischarge. Eighteen patients received
      metoprolol (5 mg IV on admission followed by 50 mg BID). SAECG recordings were
      obtained serially using an ART system (40-250 Hz filter, noise < 0.5 mV) prior to
      thrombolytic therapy, after 48 hours and after 10 days. LP was defined as posi
      tive if the SAECG met at least 2 of the Gomes criteria. Changes observed in SAECG
      recordings after thrombolytic therapy were correlated with angiographic and
      clinical data with regard to the usage of BB. The frequencies of LP before and
      after thrombolytic therapy were compared with the McNemar test. There were no
      significant differences between the clinical characteristics, risk factors, and
      angiographic findings (including infarct related artery patency and LV functions)
      of the groups. Baseline SAECG findings were also similar between the groups. The
      incidence of LP significantly decreased after TT in the BB group, however, this
      change was not observed in patients who did not receive BB (P = 0.012, McNemar
      test). Beta-blockers reduce the incidence of LPs following thrombolytic therapy
      in patients with anterior AMI. This might be explained by the possible beneficial
      effect of BB on the arrhythmogenic substrate.

PMID- 14973347
TI  - Mid to long-term results of circumflex coronary artery revascularization with
      left internal thoracic artery grafts.
AB  - The current trend in coronary artery surgery is to revascularize the left
      coronary artery branches with bilateral internal thoracic arteries (ITA). For
      this procedure, the right ITA is usually grafted to the left anterior descending
      coronary artery while the circumflex coronary artery is revascularized by the
      left ITA. The mid to long-term results of the left ITA on the circumflex system
      were examined in this study. Forty of 48 patients operated on between 1996 and
      1998 who had undergone revascularization of the left coronary artery with both
      ITAs and who fulfilled the study criteria underwent control coronary
      arteriography to determine the mid to long-term patency of LITA grafts on the
      circumflex artery. The median time for follow-up was 53 months (range, 49 to 70
      months). Of the 40 angiographically controlled patients, 35 had patent left ITA
      to circumflex artery anastomosis (87.5%). One graft stenosis and four graft
      occlusions were observed. In the same group, right ITA to left anterior
      descending coronary artery anastomoses were patent in 38 patients (95%). Left ITA
      grafts seem to be the conduit of choice for revascularization of the circumflex
      coronary artery. In combination with the in situ right ITA to left anterior
      descending coronary artery anastomosis, in situ left ITA grafting to the
      circumflex system can be done with acceptably low mortality and excellent long
      term patency rates. Its utilization is particularly advised in young patients
      where the importance of left coronary artery revascularization by bilateral ITA
      grafts is increased.

PMID- 14973348
TI  - Effect of adjunctive tirofiban therapy on angiographic and clinical outcomes in
      patients with ST-segment elevated acute myocardial infarction undergoing primary
      stenting.
AB  - The benefit of primary percutaneous coronary intervention is limited by a 5% to
      20% incidence of suboptimal epicardial coronary blood (< or = TIMI-2 flow).
      Recently, data has demonstrated that when administered in conjunction with
      primary stenting for the treatment of acute myocardial infarction (AMI),
      abciximab improves the success rate of the stenting procedure and provides
      additional clinical benefits. But data on a combination of tirofiban and primary
      stenting for treatment of ST-segment elevated (ST-se) AMI is unknown. Between May
      1999 and September 2000, primary stenting without adjunctive tirofiban therapy
      was performed in 136 consecutive patients (control group) with ST-se AMI. Between
      January 2001 and May 2002, we routinely administered tirofiban to 133 consecutive
      patients (study group) with ST-se AMI before they underwent primary stenting. The
      angiographic and clinical outcomes of both groups were compared in a
      chronologically consecutive manner. The overall mortality rate was significantly
      higher in patients with failed (< or = TIMI-2 flow) than in patients with
      successful (TIMI-3) reperfusion (20.0% vs 3.5%, P < 0.0001). Univariate analysis
      demonstrated that there were no significant differences in the successful
      reperfusion (85.7% vs 84.6%, P = 0.84) or 30-day combined end points - death,
      recurrent ischemia or reinfarction (8.3% vs 11.0%, P = 0.59) between study and
      control group patients. Clinical variables were used to statistically analyze
      potential risk factors for unsuccessful reperfusion (< or = TIMI-2 flow) in the
      study group patients. Multiple stepwise logistic regression analysis demonstrated
      that the reference lumen diameter (RLD) of the infarct-related artery (IRA) > or
      = 3.5 mm (P = 0.0004) and the lesion length of the obstruction > or = 20.0 mm (P
      = 0.018) were the significant independent predictors of failed normalized
      coronary blood flow. There were no significant differences in the restenotic rate
      of IRA (29.2% vs 30.8%, P = 0.9) or mortality rate (1.6% vs 1.6%, P = 1.0) at six
      month follow-up. In conclusion, our study demonstrates that primary stenting with
      adjunctive tirofiban therapy in ST-se AMI did not provide additional benefits in
      short-term and intermediate-term angiographic and clinical outcomes compared to
      conventional primary stenting.

PMID- 14973349
TI  - Prognostic importance of predischarged troponin T levels in acute anterior
      myocardial infarction.
AB  - The baseline cardiac troponin T (cTnT) level strongly predicts short-term
      mortality in acute coronary syndromes, but the added value of predischarged (7th
      day) measures to predict short-term outcome and left ventricular (LV) remodeling
      in patients with ST elevation myocardial infarction (MI) is controversial.
      Baseline, peak and predischarged cTnT results were evaluated in 52 patients (15
      females, 37 males, mean age, 54.4 +/- 8.8 years) with first acute anterior MI.
      There were 4 deaths (all cardiac origin) during the 30 day follow up period.
      Kaplan-Meier analysis revealed patients with a predischarged serum cTnT level
      higher than the median level (1.2 ng/mL) had a higher mortality rate than those
      with submedian levels (P < 0.05). Additionally, the highest correlation rate was
      found between predischarged cTnT values and LV ejection fraction (LV-EF, r = 
      0.58, P < 0.002). There were no differences between the groups in the 7th day
      left ventricular diastolic parameters, but the 30th day isovolumetric relaxation
      time and mitral E wave deceleration time were shorter (146.9 +/- 30.1 vs 129 +/-
      23.4 msec, P = 0.025 and, 185.8 +/- 51.8 vs 144.6 +/- 58.1 msec, P = 0.012) in
      patients with higher predischarged cTnT level. High levels of predischarged cTnT
      levels in patients admitted with first acute anterior MI defines a subgroup.
      These patients have poor systolic and diastolic functions and are at increased
      risk of short term mortality. This group of patients may have benefit from early
      intensive treatment strategies before discharge.

PMID- 14973350
TI  - Long-term follow-up after angiographically successful coronary stenting: direct
      stent versus conventional stent implantation.
AB  - The purpose of the study was to compare the impacts of angiographically
      successful direct stent implantation and conventional stent implantation (stent
      implantation following predilatation) on long-term major cardiac events. The
      authors prospectively studied 40 patients who had successful direct stent
      implantation and 46 patients who had successful conventional stent implantation.
      The end-point of the study was defined as the occurrence of a major cardiac
      event, including recurrent angina, acute myocardial infarction, death, and target
      vessel revascularization. The demographic and clinical characteristics of the
      study groups were similar, except the indication of percutaneous angioplasty,
      which was more frequently unstable angina in the conventional stent group (63% vs
      38%, P: 0.03). Procedural minor complications were more frequent in conventional
      stent implantation, and there was also a positive correlation between the
      conventional stent implantation and procedural minor complications (r = 0.231, P:
      0.03), and postprocedural troponin elevation (r = 0.221, P: 0.04). The incidences
      of major cardiac events including recurrent angina, acute myocardial infarction,
      death, death or myocardial infarction, and target vessel revascularization were
      not different between the study groups during the long-term follow-up period (21
      +/- 7.1 months for direct stent group and 20 +/- 7.5 months for conventional
      stent group). Overall end-points occurred in 9 patients (22%) in the direct stent
      group and in 9 patients (19%) in the conventional stent group. Kaplan-Meier
      survival analysis showed that there was no difference in event-free survival
      between the patients treated with direct stent implantation and conventional
      stent implantation (log-rank: 1.52, P = 0.21). Two-vessel intervention and
      hypertension were found to be related with long-term major cardiac events (r =
      0.214, P: 0.048, r = 0.206, P: 0.04, respectively). In addition to the procedural
      advantages, direct stent implantation may also provide comparable results with
      conventional stent implantation concerning the late cardiac events following
      successful percutaneous coronary angioplasty.

PMID- 14973351
TI  - Use of transesophageal atrial pacing for documentation of arrhythmias suspected
      in infants and children.
AB  - Transesophageal atrial pacing study was used to document arrhythmias in 67
      infants and children age 2 months to 16 years (mean, 8.3 years), who had
      palpitations or symptoms suggesting tachyarrhythmias but had no
      electrocardiographic documentation of cardiac dysrhythmias. The transesophageal
      pacing and medical records were reviewed retrospectively. In 47 of 67 (70%) of
      the infants and children with suspected tachyarrhythmias, transesophageal atrial
      pacing induced various tachycardias, which may be the cause of symptoms. In 10 of
      67 patients, tachycardia was induced during infusion of isoproterenol. During the
      study, tachycardia was initiated in 14 of 15 patients less than < 6 years-old and
      in 33 of 52 patients > or = 6 years-old (P < 0.05). Of these induced
      tachycardias, 25 of 47 were atrioventricular reciprocating tachycardia, 16
      atrioventricular nodal reentrant tachycardia, and 6 idiopathic left ventricular
      tachycardia. Both transesophageal study and invasive electrophysiologic study
      were performed in 10 patients. The mechanisms of tachycardia in the invasive
      study and transesophageal study were identical except for one patient. In
      conclusion, transesophageal atrial pacing and recording was less invasive, safe
      and useful for documenting arrhythmias in infants and children who had symptoms
      suggesting tachyarrhythmias, especially in patients < 6 years of age. Evaluation
      of the mechanism of induced tachycardia provided useful information regarding the
      prognosis and therapeutic options in infants and children.

PMID- 14973352
TI  - Right ventricular endomyocardial biopsy findings in 25 patients with sick sinus
      syndrome.
AB  - A variety of myocardial lesions have been demonstrated in atrial muscle in
      patients with sick sinus syndrome (SSS), but the right ventricular myocardium has
      not been studied in detail in a large series. Therefore, we performed right
      ventricular endomyocardial biopsies in 25 patients with SSS (SSS group), and the
      presence or absence of ventricular myocardial lesions was determined
      histologically. As a control, biopsies of corresponding sites in 12 normal
      autopsied hearts were obtained (N group). The mean cardiac myocyte transverse
      diameter was 14.2 +/- 3.6 microm in the SSS group and 11.7 +/- 3.1 microm in the
      N group (P < 0.01). In the SSS group, cardiac myocyte hypertrophy was observed in
      20 of 25 subjects (80%), and myocyte size variation was more frequent. Although
      the difference was not significant, myocyte disorganization, myocytolysis,
      nuclear deformity, interstitial large mononuclear cell proliferation, and
      endocardial lesions, which were not seen in the N group, were observed in the SSS
      group. A variety of myocardial lesions, including cardiac myocyte hypertrophy,
      are present not only in atrial, but also in ventricular muscle in SSS.

PMID- 14973353
TI  - Pulmonary vein dimensions and variation of branching pattern in patients with
      paroxysmal atrial fibrillation using magnetic resonance angiography.
AB  - Pulmonary veins are the most frequent origin of focal and paroxysmal atrial
      fibrillation. Although radiofrequency ablation has been attempted for the
      treatment of focal and paroxysmal atrial fibrillation, the anatomy of the
      pulmonary vein is still not fully understood. To investigate the dimensions and
      anatomical variation of the pulmonary vein in patients with paroxysmal atrial
      fibrillation, we performed breath-hold gadolinium enhanced magnetic resonance
      (MR) angiography using a 1.5 T cardiac MR imager (GE CV/i) in 32 patients with
      paroxysmal atrial fibrillation (61 +/- 8 years old), 11 patients with chronic
      atrial fibrillation (64 +/- 9 years old), and 26 patients with normal sinus
      rhythm (55 +/- 15 years old). Three dimensional images of the pulmonary veins
      were thus obtained, and the diameters of the most proximal portion of the left or
      right superior pulmonary vein and left or right inferior pulmonary vein were
      measured. Pulmonary vein branching variations were determined by a visual
      qualitative analysis by two separate readers' agreements, who were blinded to any
      clinical information. We focused on the existence of a complex-branching pattern
      draining into the orifice of four pulmonary veins. Patients with either
      paroxysmal atrial fibrillation or chronic atrial fibrillation showed larger
      superior pulmonary veins than those with normal sinus rhythm (mean +/- SD; in the
      left superior pulmonary vein, 20 +/- 3 mm, 23 +/- 3 mm vs 16 +/- 3 mm, P < 0.05;
      in right superior pulmonary vein, 19 +/- 4 mm, 19 +/- 2 mm vs 16 +/- 2 mm, P <
      0.05). Complex-branching pattern was frequently observed in inferior pulmonary
      veins in patients with either paroxysmal atrial fibrillation or chronic atrial
      fibrillation; 25/32 patients with paroxysmal atrial fibrillation, 11/11 patients
      with chronic atrial fibrillation, compared to 7/26 patients with normal sinus
      rhythm. Complex-branching patterns were not observed in superior pulmonary veins
      in any patients in this cohort. CONCLUSION: In patients with paroxysmal atrial
      fibrillation or chronic atrial fibrillation, significant pulmonary vein dilation
      occurred mainly in the superior pulmonary veins, while a complex-branching
      pattern was frequently observed in the inferior pulmonary veins. These MR
      angiographic findings might be useful when performing radiofrequency ablation
      procedures and catheter manipulation for the treatment of paroxysmal atrial
      fibrillation.

PMID- 14973354
TI  - Angiotensin-converting enzyme inhibitors are not effective at inhibiting further
      fibrous changes in the atria in patients with chronic atrial fibrillation:
      speculation from analysis of the time course of fibrillary wave amplitudes.
AB  - To examine whether angiotensin-converting enzyme (ACE) inhibitors are effective
      at inhibiting further fibrous changes in atria in patients with chronic atrial
      fibrillation, we retrospectively evaluated the time course of fibrillatory wave
      amplitudes and the effects of an ACE inhibitor on the changes. We reviewed
      medical records and electrocardiographic files. The patients were eligible for
      inclusion if they had chronic atrial fibrillation for more than 10 years. The
      fibrillatory wave with the greatest amplitude was measured in lead V1 of standard
      electrocardiograms. A total of 31 patients were enrolled and were divided into
      two groups according to treatment. Twelve patients were classified as the ACE
      inhibitor group and 19 as the non-ACE inhibitor group. There was no significant
      difference in the mean value of the fibrillatory wave amplitude at baseline
      between the 2 groups (ACE inhibitor group, 0.23 +/- 0.02 mV; non-ACE inhibitor
      group, 0.18 +/- 0.02 mV). The fibrillatory wave amplitude decreased significantly
      after 10 years in both groups (ACE inhibitor group, 0.10 +/- 0.02 mV; non-ACE
      inhibitor group, 0.11 +/- 0.01 mV) and the changes in the fibrillatory wave
      amplitude were similar between the 2 groups. These results suggest that ACE
      inhibitors are not effective at inhibiting further fibrous changes in atria in
      patients with chronic atrial fibrillation.

PMID- 14973355
TI  - Right ventricular and tricuspid valve function in patients with two ventricular
      pacemaker leads.
AB  - Existing data on the effect of retained pacemaker leads on right ventricular (RV)
      and tricuspid valve function is limited. OBJECTIVE: In this echocardiographic
      study we investigated the long-term effect of retained ventricular leads on RV
      and tricuspid valve function in patients with permanent pacemakers. Forty
      patients, 18 with two (group I) and 22 with one (group II) ventricular lead were
      assessed echocardiographically at an average of 39 months after the second lead
      implantation in group I and 80 months after the lead implantation in group II.
      The sum of the lead body diameter in group I was significantly greater than the
      body diameter in group II (P < 0.000). There was no significant difference
      between the groups with respect to chamber diameters and ventricular or valvular
      functions. The distributions of the different tricuspid regurgitation (TR) grades
      were similar, with the majority of patients in both groups having mild TR.
      Retained second pacemaker leads do not have an additional negative effect on
      right ventricular and tricuspid valve function.

PMID- 14973356
TI  - Lack of association between perlecan gene intron 6 BamHI polymorphism and risk of
      mitral valve prolapse in Taiwan Chinese.
AB  - Abnormalities of proteoglycan, collagen, and elastic fibers were found in floppy
      mitral valves. Perlecan is one of the three major classes of heparan sulfate
      proteoglycans within the cardiovascular system. The role of perlecan genetic
      variant in mitral valve prolapse (MVP) has not been studied. We therefore
      performed a case-controlled study investigating the possible relation between the
      perlecan gene intron 6 BamHI polymorphism and MVP among the Chinese population in
      Taiwan. We studied 100 patients with MVP diagnosed by echocardiography and 100
      age- and sex-matched normal control subjects. The perlecan gene intron 6 BamHI
      polymorphism was identified by polymerase chain reaction-based restriction
      analysis. There were no significant differences in either the genotype
      distribution or allelic frequencies between MVP cases and controls for perlecan
      gene intron 6 BamHI polymorphism (P = 0.20 and 0.76, respectively). Further
      categorization of the MVP patients into mild and severe subgroups also revealed
      no statistical difference from controls for perlecan gene intron 6 BamHI
      polymorphism. It is concluded that perlecan gene intron 6 BamHI polymorphism is
      not a suitable genetic marker of MVP in Taiwan Chinese.

PMID- 14973357
TI  - Cardiovascular disease risk factors in post-menopausal women in West Anatolia.
AB  - Cardiovascular risk factors are important causes of morbidity and mortality in
      postmenopausal women. The aim of this cross-sectional study was to evaluate the
      cardiovascular risk factors in 207 postmenopausal Turkish women over 45 years old
      in a rural district of West Anatolia, Manisa Muradiye district. A questionnaire
      on socioeconomic and sociodemographic characteristics was conducted in the women
      followed by the measurement of blood pressure, fasting blood glucose, cholesterol
      levels, and waist-hip ratio along with an electrocardiogram (ECG). The European
      Cardiology Society risk index was used for cardiovascular risk evaluation. The
      results showed that 86% percent of the women will be carrying more than a 5%
      probability of developing a cardiovascular risk in the next 10 years. Moreover,
      the results proved 7% of the women are at high risk for a cardiovascular
      condition. Hypertension, hypercholesterolemia, and impaired glucose tolerance,
      were observed in 62%, 35.3%, and 13.5% of the women, respectively. Seven percent
      had smoked for at least six months. Fourteen cases had complained of exercise
      angina and pathologic ECG signs were diagnosed in one-third of these 14 cases.
      The waist-hip ratio measured 0.8 or more in 66.2% of the cases, with a range of
      68-147 cm (mean; 95.6 +/- 11.55). The results indicate that the risk of a
      cardiovascular condition developing is extremely high in postmenopausal West
      Anatolian women and increases with age. Morever, the prevalance of hypertension
      increased with age and was very closely related with low socioeconomic levels.
      These hazardous cardiovascular disease risk factors should be considered as high
      priority health problems in rural and low socioeconomic areas of developing
      communities. Intervention to modify the cardiovascular risk factors should be
      included in routine primary health care programs.

PMID- 14973358
TI  - Cell cycle regulator expression after coronary stenting in humans.
AB  - Proliferation of vascular smooth muscle cells (VSMCs) is under the control of
      cell cycle regulator activity, which is induced by several growth factors. Recent
      attention has been drawn to treatments that target cell cycle regulators to
      prevent the proliferation of VSMCs after coronary angioplasty. However,
      histopathological evaluation of cell cycle regulator expression after human
      coronary stenting has not been sufficient. Thirty-one coronary arteries of 23
      cadavers were examined. Time from stent implantation to patient death ranged from
      0 to 235 days. Sections were stained with antibodies against platelet-derived
      growth factor (PDGF), basic fibroblast growth factor (b-FGF), cyclin D1, p16,
      p21, and p27. Staining for macrophage colony stimulating factor receptor (MCSF-R)
      was conducted to detect dedifferentiated VSMCs. MCSF-R-positive cells were
      observed in neointima but decreased in the late stage. PDGF was detected in
      neointima and decreased gradually. Expression of cyclin D1 appeared to be
      associated with the proliferation of VSMCs, whereas p27 was downregulated with
      the proliferation of neointima and upregulated in the late stage. Our results
      suggest that one of the most promising methods for preventing excessive
      proliferation of neointima after stenting is to limit the decrease in p27 or the
      increase in cyclin D1.

PMID- 14973359
TI  - A case report of late coronary stent thrombosis manifested as acute myocardial
      infarction 19 months after stenting.
AB  - A 63-year-old Japanese man was readmitted to our hospital due to acute broad
      anterior myocardial infarction (AMI). The proximal left anterior descending
      artery (LAD) at the prior stent, which was implanted 19 months earlier and in
      which no angiographic restenosis was recognized 13 months before the second
      study, was totally occluded. After crossing a guide wire and balloon angioplasty,
      angiographic radiolucency was observed at the prior stent, suggesting that AMI
      was induced by late coronary stent thrombosis. Intravascular ultrasound performed
      19 days after the onset of AMI revealed superficial calcification without
      significant stenosis and an atherosclerotic plaque distal to the stent that was
      not significantly changed compared to 19 months previously, consistent with the
      culprit lesion being an intrastent site. AMI may thus be induced by late coronary
      stent thrombosis during long-term clinical follow-up without clinical symptoms or
      angiographic restenosis at the second study.

PMID- 14973360
TI  - A patient with bicuspid aorta and intercoronary continuity: a rare and variant of
      coronary circulation.
AB  - Bidirectional flow in patients with normal coronary arteries is an indicator of
      intercoronary continuity, a rare variant of coronary circulation, distinct from
      collaterals. The case of an 18 year old Turkish male with bicuspid aorta and
      intercoronary artery is reported and different aspects of this interesting entity
      are emphasized.

PMID- 14973361
TI  - Combination therapy for adult coronary artery aneurysm with off-pump coronary
      artery bypass grafting and vein graft-coated stent.
AB  - We report on a 51-year-old Japanese female with bilateral coronary artery
      aneurysms. Severe calcified aneurysms were detected in the proximal right
      coronary artery (RCA) and left anterior descending branch (LAD). The RCA was
      totally occluded and supplied by the blood flow via septal branches of the LAD. A
      two-stage management plan, including an off-pump coronary artery bypass grafting
      for the RCA with a right gastroepiploic artery and catheter angioplasty with an
      autologous vein graft-coated stent for the LAD, was successfully completed.
      Prophylactic treatments for coronary artery aneurysm are still controversial,
      therefore, minimal invasive procedures should be favored to prevent acute cardiac
      shock or sudden death related to aneurysmal obstruction.

PMID- 14973362
TI  - Brugada-like electrocardiographic pattern unmasked by fever.
AB  - Brugada syndrome is characterized by right bundle branch block morphology and ST
      segment elevation in the right precordial leads and a propensity to develop
      ventricular arrhythmias. Mutations in a cardiac sodium channel gene have been
      linked to this syndrome, and the ionic mechanisms responsible for the
      electrocardiographic phenotype are temperature-dependent. This case report
      describes a patient in whom a typical Brugada ECG pattern developed during fever
      and could be reproduced at normal body temperature by administration of
      pilsicainide.

PMID- 14973363
TI  - Carvedilol therapy improved left ventricular function in a patient with
      arrhythmogenic right ventricular cardiomyopathy.
AB  - An asymptomatic 35 year-old man was referred to our hospital because of abnormal
      ECG findings. The ECG showed complete right bundle branch block and left anterior
      hemiblock. Echocardiography revealed a moderately enlarged right ventricle (RV)
      and an apical aneurysm. RV wall motion showed diffusely moderate impairment,
      while the systolic function of the left ventricle (LV) was slightly decreased.
      The ejection fractions (EF) of the RV and LV were calculated as 28.1% and 41.9%
      by Simpson's method using multiple cardiac computed tomography (CT) scans. A 24
      hour ambulatory ECG showed only 372 single premature ventricular contractions
      (PVC). Cardiac catheterizaion revealed that the RV was enlarged with prominent
      trabeculation and decreased motion. In an electrophysiologic study, neither
      electrical stimulation of the RV nor electrical stimulation plus isoproterenol
      infusion could induce ventricular tachycardia. Pathological examination of a
      biopsy from the interventricular septum of the RV revealed fibrofatty change in
      the myocardium. Based on these results, we made a diagnosis of arrhythmogenic
      right ventriclular cardiomyopathy (ARVC) and administered 5 mg of carvedilol.
      Sixty days after the initiation of carvedilol therapy, we performed repeat
      cardiac CT. The EF of the LV was markedly improved from 41.9% to 62.0%, although
      the EF of the RV was not changed. The number of PVCs showed no change. This case
      suggests that carvedilol is not only useful for controlling arrhythmia but also
      for improving left ventriclular function in some patients with ARVC. Sympathetic
      overactivity is reported to cause sudden death, so carvedilol may be a first-line
      drug for some patients with ARVC.

PMID- 14973364
TI  - Comparison of two tests for serum alpha-galactosidase in nonneuromuscular left
      ventricular hypertrabeculation/concompaction.

PMID- 14973366
TI  - Synthesis of radioactive and photoactivable ganglioside derivatives for the study
      of ganglioside-protein interactions.
AB  - The procedures for the preparation of radioactive and photoactivable ganglioside
      derivatives have been continuously developed from 1989, when for the first time
      the synthesis of photoactivable tritium labeled GM1 ganglioside was presented. We
      described previously the synthesis of photoactivable derivatives of GM3 and GM1
      gangliosides, tritium-labeled at acetyl group of sugar units, and of
      photoactivable GM1 and GD1b gangliosides, tritium-labeled at position 6 of the
      external galactose. These procedures are reviewed in detail in the present paper.
      The use of these ganglioside derivatives to study the ganglioside-protein
      interactions and to identify proteins that specifically interact with
      gangliosides (including GPI-anchored proteins of the outer membrane leaflet,
      proteins anchored to the cytoplasmic side of the plasma membrane through a fatty
      acyl chain, transmembrane proteins, and soluble cytoplasmic proteins) is
      discussed.

PMID- 14973367
TI  - A turn in the road: How studies on the pharmacology of glucosylceramide synthase
      inhibitors led to the identification of a lysosomal phospholipase A2 with
      ceramide transacylase activity.
AB  - A series of inhibitors of glucosylceramide synthesis, the PDMP based family of
      compounds, has been developed as a tool for the study of sphingolipid
      biochemistry and biology. During the course of developing more active
      glucosylceramide synthase inhibitors, we identified a second site of inhibitory
      activity for PDMP and its structural homologues that accounted for the ability of
      the inhibitors to raise cell and tissue ceramide levels. This inhibitory activity
      was directed against a previously unknown pathway for ceramide metabolism, viz.
      the formation of 1- O -acylceramide. In this pathway the addition of a fatty acyl
      group to the primary hydroxyl of ceramide occurs through a transacylation with
      either phosphatidylethanolamine or phosphatidylcholine as a substrate. However,
      both in the absence and presence of ceramide, water serves as an acceptor for the
      fatty acid. Thus the enzyme may be considered to be a phospholipase A2. The
      enzyme is unique in that it has an acidic pH optimum and is localized to
      lysosomes by cell fractionation. More recently, the 1- O -acylceramide synthase
      has been purified, sequenced, and cloned. This phospholipase A2 was discovered to
      be structurally homologous to lecithin cholesterol acyltransferase (LCAT).
      However, this phospholipase A2 does not recognize cholesterol and lacks the
      defined lipoprotein-binding domain present in LCAT. We now refer to this enzyme
      as lysosomal phospholipase A2 (LPLA2). Although acidic phospholipase A2
      activities have been previously identified, LPLA2 appears to be the first
      lysosomal PLA2 to have been sequenced. This new phospholipase A2 lacks an obvious
      and proven biological function.

PMID- 14973368
TI  - Generation of receptor-active, globotriaosyl ceramide/cholesterol lipid 'rafts'
      in vitro : A new assay to define factors affecting glycosphingolipid receptor
      activity.
AB  - Purified renal globotriaosyl ceramide (Gb3)/cholesterol mixtures sonicated heated
      in a Triton-containing buffer placed below a discontinuous sucrose gradient form
      glycosphingolipid (GSL)-containing dense lipid structures at the 30/5% sucrose
      interface after centrifugation. Inclusion of fluorescein-labeled verotoxin 1 B
      subunit (FITC-VT1 B) within the most dense sucrose layer results in the
      fluorescent labeling of this Gb3-containing raft structure. Alternatively
      inclusion of I-labeled VT1 fractionation allows quantitation of binding. FITC-VT1
      B effectively competes for I-VT1/Gb3 raft binding. This assay will allow the
      definition of the optimal raft composition for VT1 (or any other ligand) binding.
      The effect of several potential cellular raft components are reported. Increased
      cholesterol content increased VT1 binding. Addition of phosphatidylethanolamine
      had minimal effect while phosphatidylserine was inhibitory. Although inclusion of
      sphingomyelin increased the Gb3 content of the "raft" reduced VT1 binding was
      seen. Inclusion of other glycolipids can also be inhibitory. The addition of
      globotetraosyl ceramide had no effect; however addition of sulfogalactosyl
      ceramide but not sulfogalactoglycerolipid inhibited VT1/Gb3 raft binding. These
      results suggest that certain GSLs can disfavor the formation of the appropriate
      'raft' structure for ligand binding that this is dependent on both their
      carbohydrate lipid structure. Such "deceptor" GSLs may provide an as yet
      unappreciated mechanism for the regulation of cellular GSL receptor activity.
      This model is an effective tool to approach the dynamics ligand-binding
      specificity of GSL/cholesterol-containing lipid microdomains.

PMID- 14973369
TI  - Glycosphingolipids and cell death.
AB  - Sphingolipids have been implicated in various cellular processes including
      growth, cell-cell or ligand-receptor interactions, and differentiation. In
      addition to their importance as reservoirs of metabolites with important
      signaling properties, sphingolipids also help provide structural order to plasma
      membrane lipids and proteins within the bilayer. Glycosylated sphingolipids, and
      sphingomyelin in particular, are involved in the formation of lipid rafts.
      Although it is well accepted that ceramide, the backbone of all sphingolipids,
      plays a critical role in apoptosis, less is known about the biological functions
      of glycosphingolipids. This review summarizes current knowledge of the
      involvement of glycosphingolipids in cell death and in other pathological
      processes and diseases.

PMID- 14973370
TI  - Ganglioside/protein kinase signals triggering cytoskeletal actin reorganization.
AB  - Exposure of neuronal cells to nanomolar concentrations of oligosaccharide
      portions of ganglioside GM2 and GT1b stimulates cAMP-dependent protein kinase
      (PKA) Ca2+/calmodulin-dependent protein kinase II (CaMKII), respectively, in a
      few seconds suggesting the presence of glyco-receptor-like molecules on the
      surface of the cells. Both GM2/PKA (GalNAc/PKA) and GT1b/CaMKII signaling
      cascades induced cytoskeletal actin reorganization through Cdc42 activation
      leading to filopodia formation within 2 min. Long-term effects of these glyco
      signals were facilitation of dendritic differentiation of primary cultured
      hippocampal neurons and cerebellar Purkinje neurons indicating physiological
      roles of the signals in neuronal differentiation and maturation.

PMID- 14973371
TI  - Alzheimer's beta-secretase cleaves a glycosyltransferase as a physiological
      substrate.
AB  - Alzheimer's beta-secretase (BACE1) is a membrane-bound protease that cleaves the
      amyloid precursor protein (APP) in the trans-Golgi network, an initial step in
      the pathogenesis of Alzheimer's disease. Although BACE1 is distributed among
      various tissues including brain, its physiological substrate other than APP have
      not been identified. We have recently found that when BACE1 was overexpressed in
      COS cells together with alpha2,6-sialyltransferase (ST6Gal I), the secretion of
      ST6Gal I markedly increased, suggesting that BACE1 cleaves ST6Gal I as a
      physiological substrate. Thus BACE1 is the first identified protease that is
      responsible for the cleavage and secretion of glycosyltransferases.

PMID- 14973372
TI  - Expression profiling of human breast cancers and gene regulation by progesterone
      receptors.
AB  - Even the first expression profiling studies of breast cancers have generated new
      insights. They suggest for example, that information about tumor aggressiveness,
      prognosis, metastatic potential, or treatment outcome is encoded in, and can be
      deduced from, the primary tumor. On the other hand no clinical genomic array data
      have yet been published that deal with hormonal aspects of breast tumorigenesis,
      tumor progression, or therapeutics. Rather, studies have focused on experimental
      model systems. We review below the currently published data on array profiling in
      clinical breast cancer, then describe our studies in breast cancer cell lines and
      xenograft models dealing with progesterone receptors (PRs) and the role of
      progesterone. We demonstrate that the two PR isoforms, PR-A and PR-B, have mostly
      nonoverlapping molecular signatures when liganded by progesterone, with PR-B the
      more active form. Additionally, we document the surprising finding that
      unliganded PRs can regulate gene transcription, with PR-A the more active form.
      In ovariectomized mice supplemented with estradiol but lacking measurable
      progesterone, PR-B-expressing tumors grow to twice the size of PR-A-expressing
      ones. We conclude that in breast cancers, PRs are more than simple markers of
      estrogen receptor function. Rather, presence of PRs and the ratio of the two
      isoforms directly influence tumor phenotype, even in the absence of ligand.

PMID- 14973373
TI  - Using gene expression arrays to elucidate transcriptional profiles underlying
      prolactin function.
AB  - Prolactin is an ancient hormone, with different functions in many species. The
      binding of prolactin to its receptor, a member of the cytokine receptor
      superfamily, results in the activation of different intracellular signaling
      pathways, such as JAK2/STAT5, MAP kinase, and PI3K/AKT. How prolactin elicits so
      many different biological responses remains unclear. Recently, microarray
      technology has been applied to identify prolactin target genes in different
      systems. Here, we attempt to summarize and compare the available data. Our
      comparison of the genes reported to be transcriptionally regulated by prolactin
      indicates that there are few genes in common between the different tissues. Among
      the organs studied, mammary and prostate glands displayed the largest number of
      overlaps in putative prolactin target genes. Some of the candidates have been
      implicated in tumorigenesis. The relevance and validation of microarray data, as
      well as comparison of the results obtained by different groups, will be
      discussed.

PMID- 14973374
TI  - Functional development of the mammary gland: use of expression profiling and
      trajectory clustering to reveal changes in gene expression during pregnancy,
      lactation, and involution.
AB  - To characterize the molecular mechanisms by which progesterone withdrawal
      initiates milk secretion, we examined global gene expression during pregnancy and
      lactation in mice, focusing on the period around parturition. Trajectory
      clustering was used to profile the expression of 1358 genes that changed
      significantly between pregnancy day 12 and lactation day 9. Predominantly
      downward trajectories included stromal and proteasomal genes and genes for the
      enzymes of fatty acid degradation. Milk protein gene expression increased
      throughout pregnancy, whereas the expression of genes for lipid synthesis
      increased sharply at the onset of lactation. Examination of regulatory genes with
      profiles similar or complementary to those of lipid synthesis genes led to a
      model in which progesterone stimulates synthesis of TGF-beta, Wnt 5b, and IGFBP-5
      during pregnancy. These factors are suggested to repress secretion by interfering
      with PRL and IGF-1 signaling. With progesterone withdrawal, PRL and IGF-1
      signaling are activated, in turn activating Akt/PKB and the SREBPs, leading to
      increased lipid synthesis.

PMID- 14973375
TI  - Microarray analysis of the involution switch.
AB  - Mammary epithelial cells (MEC) undergo a series of developmental decisions during
      a pregnancy cycle. The switches from proliferation to differentiation to
      secretion and then to cell death are precisely controlled. In order to identify
      critical changes associated with the transition from a secretory phenotype during
      lactation to dedifferentiation and cell death, we have undertaken a microarray
      analysis of mouse mammary gland development. We have focused on the involution
      switch and on the transcription profiles of genes that are targets of
      transcription factors known to influence involution and apoptosis. Our results
      show that both Stat3 and NF-kB target genes are induced by the involution switch
      while Stat5 target genes are distinct from Stat3 induced genes. Furthermore, a
      substantial number of genes that were specifically upregulated at the start of
      involution are regulators of inflammation and the acute phase response. These
      results provide a novel insight into the involution process and demonstrate the
      value of microarray analysis in defining molecular events associated with
      critical developmental transitions in mammary gland.

PMID- 14973376
TI  - Interrogating mouse mammary cancer models: insights from gene expression
      profiling.
AB  - Numerous mouse models for mammary cancer have been developed and characterized
      based upon their biological, molecular, and histopathological features. In an
      effort to dissect the molecular anatomy of such models and compare their gene
      expression profiles to those of human breast cancer, six models representing
      various oncogenic pathways have been investigated using cDNA microarray
      technology. Results of these analyses are presented and discussed in the context
      of technological challenges presented by analyzing data on such a large scale.
      Further expression profiling coupled with emerging proteomic technologies will
      more completely define and distinguish mouse models of mammary cancer from each
      other and provide a comprehensive basis for comparing such models with the human
      disease they are intended to represent.

PMID- 14973377
TI  - Laser capture microdissection and advanced molecular analysis of human breast
      cancer.
AB  - Advances in comprehensive genomic and proteomic technologies are providing
      researchers with an unprecedented opportunity for high-throughput molecular
      analysis of human breast cancer. Adaptation of these technologies to laser
      capture microdissection (LCM) is poised to exert dramatic change on the pace of
      breast cancer research. Although technical limitations have impeded the coupling
      of these high-throughput technologies to LCM, recent advances have allowed for
      the successful application of this cellular-based approach to breast cancer, and
      the results of such studies have provided researchers with unique insight into
      the disease. This approach holds great potential for rapid advancement in our
      understanding of breast cancer, and it is hoped that such advancements will lead
      to novel predictive and therapeutic strategies for women with the disease. This
      review outlines the current status of the adaptation of advanced molecular
      technologies to LCM and highlights recent studies in which this approach has been
      applied to human breast cancer.

PMID- 14973378
TI  - Tissue microarrays.
AB  - High-throughput tissue microarray (TMA) technology facilitates the assessment of
      the clinical relevance of molecular markers by enabling the simultaneous analysis
      of hundreds of tissue specimens. The widespread adoption of TMAs in many
      laboratories replaces the conventional one-slide-one-section approach, in which
      individual archival clinical specimens were placed on separate microscope slides,
      with the ability to assess RNA, DNA, or protein expression in hundreds of
      individual patient specimens in a single experiment. One of the applications of
      this technology is to significantly accelerate advances in translational research
      through more efficient assessment of novel markers of outcome and response, and
      as a result, a more rapid application of this knowledge to clinical practice.

PMID- 14973379
TI  - Statistical issues in the design and analysis of gene expression microarray
      studies of animal models.
AB  - Appropriate statistical design and analysis of gene expression microarray studies
      is critical in order to draw valid and useful conclusions from expression
      profiling studies of animal models. In this paper, several aspects of study
      design are discussed, including the number of animals that need to be studied to
      ensure sufficiently powered studies, usefulness of replication and pooling, and
      allocation of samples to arrays. Data preprocessing methods for both cDNA dual
      label spotted arrays and Affymetrix-style oligonucleotide arrays are reviewed.
      High-level analysis strategies are briefly discussed for each of the types of
      study aims, namely class comparison, class discovery, and class prediction. For
      class comparison, methods are discussed for identifying genes differentially
      expressed between classes while guarding against unacceptably high numbers of
      false positive findings. Various clustering methods are discussed for class
      discovery aims. Class prediction methods are briefly reviewed, and reference is
      made to the importance of proper validation of predictors.

PMID- 14973380
TI  - Historical and epidemiologic background of human premalignant breast disease.
AB  - Premalignant breast disease in humans is a concept that admits to a broad range
      of elements and possible determinants predicting the likelihood of developing
      breast cancer. Most of these elements are relative, such as the risk of breast
      cancer for women that is 130 times that of men and peaks at a younger age by
      about 10 years. Breast cancer is clearly a stochastic, multifactorial process
      that evolves over many years in which we must make predictions by likelihood.
      This review will present the most specially defined and reliably proven of these
      elements, highlighting anatomic and molecular factors.

PMID- 14973382
TI  - Culture models of human mammary epithelial cell transformation.
AB  - Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS)
      already display several of the aberrant phenotypes found in primary breast
      cancers, including chromosomal abnormalities, telomerase activity, inactivation
      of the p53 gene, and overexpression of some oncogenes. Efforts to model early
      breast carcinogenesis in human cell cultures have largely involved studies of in
      vitro transformation of normal finite lifespan human mammary epithelial cells
      (HMEC) to immortality and malignancy. We present a model of HMEC immortal
      transformation consistent with the known in vivo data. This model includes a
      recently described, presumably epigenetic process, termed conversion, which
      occurs in cells that have overcome stringent replicative senescence and are thus
      able to maintain proliferation with critically short telomeres. The conversion
      process involves reactivation of telomerase activity, and acquisition of good
      uniform growth in the absence and presence of TGFbeta. We propose that overcoming
      the proliferative constraints set by senescence, and undergoing conversion,
      represent key rate-limiting steps in human breast carcinogenesis, and occur
      during early stage breast cancer progression.

PMID- 14973381
TI  - Biological features of premalignant disease in the human breast.
AB  - Most human invasive breast cancers (IBCs) arise from preexisting benign lesions.
      There are many types of benign lesions in the human breast and only a few appear
      to have significant premalignant potential (atypical hyperplasias and in situ
      carcinomas). These lesions are relatively common and only a small proportion
      progress to IBC. They are currently defined by their histological features and
      their prognosis is imprecisely estimated from indirect evidence based on
      epidemiological studies. Although lesions within specific categories look alike,
      they must possess morphologically silent biological differences motivating some
      to remain stable and others to progress. Understanding the biological changes
      responsible for the development and progression of premalignant disease is a very
      active area of medical research. Progress in this area may provide new
      opportunities for breast cancer prevention by providing strategies to treat
      premalignant lesions before they develop or become cancerous. A large number of
      biological features have been evaluated in this setting during the past decade.
      This review discusses a few features that appear to be particularly important and
      have been studied in a relatively comprehensive manner.

PMID- 14973383
TI  - Xenograft models of premalignant breast disease.
AB  - Dysplastic and hyperplastic proliferative lesions with graded severity of atypia
      are recognized in a number of tissues and are generally suspected to be
      premalignant, that is to say at high risk for further progressing to carcinoma in
      situ and invasive cancer. However, few xenograft models of premalignancy for any
      organ site have been successfully developed. A good model of human premalignant
      breast disease would lead to lesions which resemble high risk human breast
      disease in xenografts and sporadically progress to invasive cancer with time. In
      this chapter the use of breast tissue pieces and epithelial cells for
      establishment of xenografts and the development of human breast epithelial cell
      lines that form premalignant xenograft lesions are described. MCF10AT cells not
      only form simple differentiated ducts which persist in xenografts and
      sporadically progress to carcinoma, but also form intermediate proliferative
      lesions resembling proliferative disease without atypia, atypical hyperplasia,
      and carcinoma in situ.

PMID- 14973384
TI  - The preneoplastic phenotype in murine mammary tumorigenesis.
AB  - Preneoplastic lesions in murine mammary tumorigenesis have been extensively
      investigated over the past 50 years. The two general types of lesion that have
      malignant potential are the alveolar hyperplasias represented by the classical
      hyperplastic alveolar nodule and the ductal hyperplasias. The former type of
      lesion is induced by viral, chemical and hormonal agents; the latter by chemical
      agents and specific genetic alterations. Individual animal models have been
      utilized to elucidate the basic biological properties of the lesions and some of
      the basic molecular alterations. The biological phenotype of the two types of
      lesions include immortalization and epithelial hyperplasia. The ductal
      hyperplasias are distinguished from the alveolar hyperplasias by their pattern of
      epithelial hyperplasia and their extent of aneuploidy. The molecular alterations
      underlying epithelial hyperplasia are numerous and dependent on the particular
      animal model. An important issue for future studies is how faithfully any of
      these models mimic human premalignant progression. A minimal set of criteria is
      proposed that includes morphological progression, hormone dependence and genetic
      instability. It is likely that hyperplasias from a specific mouse model will
      represent a subset of the lesions found in human disease. Analogous hyperplasias
      from several defined genetic models, adequately characterized at the biological
      and molecular levels, would provide appropriate models for testing
      chemopreventive agents.

PMID- 14973385
TI  - Rat models of premalignant breast disease.
AB  - While a number of agents have been shown to induce mammary carcinogenesis in the
      rat, premalignant stages of the disease have been best characterized in
      chemically-induced models, specifically those initiated by either 7,12
      dimethylbenz[alpha]anthracene (DMBA) or 1-methyl-1-nitrosourea (MNU). In general,
      it appears that epithelial cells in mammary terminal end buds or terminal
      ductules are the targets of carcinogenic initiation, and that a series of
      morphologically identifiable steps are involved in the development of mammary
      carcinoma. The premalignant steps include ductal hyperplasia of the usual type
      and carcinoma in situ of the cribriform or comedo type; atypical ductal
      hyperplasia has not been reported. Thus the histogenesis of lesions occurring in
      chemically induced mammary carcinogenesis in the rat is similar to that observed
      in the human; although, the spectrum of lesions observed in the rat is limited.
      Opportunities to investigate the biological and molecular characteristics of
      premalignant breast disease in the rat are presented.

PMID- 14973386
TI  - Genetically engineered mouse models of mammary intraepithelial neoplasia.
AB  - Foci of atypical mammary epithelium have been associated with breast cancer in
      many species including mouse and man. The advent of targeted genomics has led to
      the creation of numerous genetically engineered mice (GEM) which display focal
      atypical lesions associated with mammary cancer. Some early lesions in GEM have a
      remarkable morphological similarity to pre-cancers in humans. While the malignant
      potential of atypical foci have been thoroughly documented in the non-GEM by
      tissue transplantation, a review of the literature reveals that precursor lesions
      in GEM remain incompletely described and only partially documented. Their
      validation as appropriate models of human breast preneoplasia awaits classical
      transplantation studies. Here, we review the literature characterizing early
      lesions of GEM models of mammary cancer, discuss the principles of the Focality,
      Atypia, and Association and present an introduction of mammary transplantation
      for model Validation.

PMID- 14973387
TI  - Biology of aromatase in the mammary gland.
AB  - While the ovaries are the principal source of systemic estrogen in the
      premenopausal nonpregnant woman, other sites of estrogen biosynthesis are present
      throughout the body and these become the major sources of estrogen beyond
      menopause. These sites include the mesenchymal cells of the adipose tissue and
      skin, osteoblasts, and perhaps chondrocytes in bone, vascular endothelial and
      aortic smooth muscle cells, as well as a number of sites in the brain including
      the medial preoptic/anterior hypothalamus, the medial basal hypothalamus and the
      amygdala. These extragonadal sites of estrogen biosynthesis possess several
      fundamental features which differ from those of the ovaries. Principally, the
      estrogen synthesized within these compartments is probably only biologically
      active at a local tissue level in a paracrine or 'intracrine' fashion. Thus the
      total amount of estrogen synthesized by these extragonadal sites may be small,
      but the local tissue concentrations achieved are probably quite high, and exert
      significant biological influence locally. Thus these sources of estrogen play an
      important but hitherto largely unrecognized, physiological and pathophysiological
      role.

PMID- 14973388
TI  - Estrogen metabolism as a regulator of estrogen action in the mammary gland.
AB  - Estrogen action in the target cells is dependent on estrogen receptor activity
      and intracellular estrogen concentration, which, in turn, is affected by the
      serum concentration and local metabolism in these cells. During the reproductive
      years the main source of estrogens is the ovarian follicles, but in
      postmenopausal women most of the estrogens are formed in peripheral tissues.
      17Beta-hydroxysteroid dehydrogenases (17HSDs) catalyze the reaction between
      17beta-hydroxysteroids and 17-ketosteroids, and several distinct 17HSD isoenzymes
      have been characterized. 17HSD type 1 catalyzes the reaction from low-activity
      estrone to high-activity estradiol. The type 2 enzyme has an opposite activity,
      thereby reducing the exposure of tissues to estrogen action. 17HSD type 1 is
      expressed both in steroidogenic tissues and in the target tissues of steroid
      action, such as normal and malignant breast tissue, where it may be responsible
      for maintaining the high intracellular estradiol concentration seen in breast
      cancer specimens. Therefore, 17HSD type 1 inhibitors may be useful in the
      treatment and/or prevention of estrogen-dependent malignancies, such as breast
      cancer. This article deals mainly with 17HSD types 1 and 2 and their role in
      estrogen action in breast tissue.

PMID- 14973390
TI  - Estrogen receptor content in malignant breast tumors in men--a review.
AB  - Male breast cancer is a rare disease and clinical or epidemiological data are
      available from only a relatively few cases. Nonetheless, both similarities and
      discrepancies are apparent between breast cancer in men and women. For example,
      lobular and mucinous carcinomas are seldom seen in men. Tumors in men more often
      display neuroendocrine differentiation, with an average age at diagnosis ten
      years later than in women. A high proportion of breast tumors in men are estrogen
      receptor-alpha positive (in this review 77%) and progesterone receptor positive
      (76%). Breast tumors in men often respond favorably to endocrine manipulation,
      including testicular ablation or antiestrogen therapy. Thus, the hormone
      receptors in these tumors can be functionally active and used for therapeutic
      intervention. This proposal has been questioned in some studies because estrogen
      dependent proteins are expressed to a lesser degree in men. Furthermore, men do
      not have a better overall breast cancer prognosis compared with women, after
      adjustments have been made for age and tumor stage. While the androgen receptor
      content has been assessed in a few studies, there are no studies on the estrogen
      receptor-beta content of breast tumors in men.

PMID- 14973389
TI  - Estrogen receptor alpha in human breast cancer: occurrence and significance.
AB  - Estrogens have long been recognized as being important for stimulating the growth
      of a large proportion of breast cancers. Now it is recognized that estrogen
      action is mediated by two receptors, and the presence of estrogen receptor alpha
      (ER alpha) correlates with better prognosis and the likelihood of response to
      hormonal therapy. Over half of all breast cancers overexpress ER alpha and around
      70% of these respond to anti-estrogen (for example tamoxifen) therapy. In
      addition, the presence of elevated levels of ER alpha in benign breast epithelium
      appears to indicate an increased risk of breast cancer, suggesting a role for ER
      alpha in breast cancer initiation, as well as progression. However, a proportion
      of ER alpha-positive tumors does not respond to endocrine therapy and the
      majority of those that do respond eventually become resistant. Most resistant
      tumors remain ER alpha-positive and frequently respond to alternative endocrine
      treatment, indicative of a continued role for ER alpha in breast cancer cell
      proliferation. The problem of resistance has resulted in the search for and the
      development of diverse hormonal therapies designed to inhibit ER alpha action,
      while research on the mechanisms which underlie resistance has shed light on the
      cellular mechanisms, other than ligand binding, which control ER alpha function.

PMID- 14973391
TI  - The normal and malignant mammary gland: a fresh look with ER beta onboard.
AB  - Estrogens are important for the development and function of the normal mammary
      gland as well as for development of mammary cancer. The frontline therapy for
      treatment of estrogen receptor (ER alpha) positive breast cancer is
      antiestrogens. A second estrogen receptor (ER beta) is also expressed in the
      breast but it has not been measured because it is not detected by the
      immunoassays used to detect ER alpha. In many cell systems ER beta has actions
      which are opposite to those of ER alpha and this finding has raised questions
      about the role of ER beta in the development and treatment of breast cancer.

PMID- 14973392
TI  - Mechanisms of inhibitory aryl hydrocarbon receptor-estrogen receptor crosstalk in
      human breast cancer cells.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that forms a functional heterodimeric complex with the AhR nuclear translocator
      (Arnt) protein. The environmental toxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), is a high affinity ligand for the AhR and has been extensively used to
      investigate AhR-mediated biochemical and toxic responses. TCDD modulates several
      endocrine pathways including inhibition of 17beta-estradiol-induced responses in
      the immature and ovariectomized rodent uterus and mammary gland and in human
      breast cancer cell lines. TCDD inhibits formation and growth of mammary tumors in
      carcinogen-induced rodent models and relatively nontoxic selective AhR modulators
      (SAhRMs) are being developed for treatment of breast cancer. The mechanisms of
      inhibitory AhR-estrogen receptor (ER) crosstalk have been investigated in MCF-7
      breast cancer cells by analysis of promoter regions of genes induced by E2 and
      inhibited by TCDD. AhR-mediated inhibition of E2-induced cathepsin D, pS2, c-fos,
      and heat shock protein 27 gene expression involves direct interaction of the AhR
      complex with inhibitory pentanucleotide (GCGTG) dioxin responsive elements
      (iDREs) resulting in disruption of interactions between proteins binding DNA
      elements required for ER action and the basal transcription machinery. Mechanisms
      of inhibitory AhR-ER crosstalk indicate that functional iDREs are required for
      inhibition of some genes; however, results indicate that other interaction
      pathways are important including AhR-mediated proteasome-dependent degradation of
      the ER.

PMID- 14973393
TI  - The role of coactivators and corepressors in the biology and mechanism of action
      of steroid hormone receptors.
AB  - Steroid hormone receptors are members of a superfamily of ligand-dependent
      transcription factors. As such they have a DNA binding domain that recognizes
      specific target gene sequences along with separate transcriptional activation
      domains. What sets steroid hormone receptors (and other nuclear hormone
      receptors) apart from other families of sequence specific transcriptional
      activators is the presence of a ligand binding domain (LBD) that acts as a
      molecular switch to turn on transcriptional activity when a hormonal ligand
      induces a conformational change in the receptor. Upon binding hormone, steroid
      receptors recruit a novel coactivator protein complex with an essential role in
      receptor-mediated transcriptional activation. Coactivators function as adaptors
      in a signaling pathway that transmits transcriptional responses from the DNA
      bound receptor to the basal transcriptional machinery. Hormone agonists induce a
      conformational change in the carboxyl-terminal transcriptional activation domain,
      AF-2, that creates a new protein interaction site on the surface of the LBD that
      is recognized by LXXLL motifs in the p160 family of coactivators. In contrast,
      steroid antagonists such as the antiestrogen tamoxifen for the estrogen receptor
      induce an alternate conformation in AF-2 that occludes the coactivator binding
      site and recruits corepressors that can actively silence steroid responsive
      genes. Thus, the cellular availability of coactivators and corepressors is an
      important determinant in the biological response to both steroid hormone agonists
      and antagonists. This paper provides an update on the properties and mechanism of
      action of nuclear receptor coactivators, the nature of the coactivator-binding
      site, and the structural and mechanistic basis for ligand-dependent binding of
      coactivators to receptors.

PMID- 14973394
TI  - A reappraisal of progesterone action in the mammary gland.
AB  - The ovarian hormones estrogen and progesterone and their respective receptors are
      essential for maintenance of postnatal developmental plasticity of the mammary
      gland and play a key role in mammary tumorigenesis. Mouse models in which
      expression of the progesterone receptors was genetically ablated have recently
      become available. Studies of these models have demonstrated that progesterone is
      specifically required for pregnancy associated ductal proliferation and
      lobuloalveolar differentiation of the mammary epithelium, but not for immediate
      postpubertal ductal morphogenesis. Use of these mice in combination with mammary
      gland transplantation indicates that developmental regulation by progesterone
      appears to occur through a paracrine mechanism in which progesterone receptor
      (PR) positive cells represent a subset of non-proliferating epithelial cells that
      are capable of directing proliferation and/or differentiation of neighboring
      receptor negative cells. The hierarchical organization of these receptors in the
      epithelium and their segregation from proliferating cells is a conserved feature
      in rodent and human mammary tissue. The identification of paracrine mediators of
      the progesterone response is now an imminent goal as is the delineation of the
      individual contributions of the two PR isoforms using similar approaches.

PMID- 14973395
TI  - The stubborn logic of regular gamblers: obstacles and dilemmas in cognitive
      gambling research.
AB  - Cognitive studies into gambling behaviour have shown that many gamblers
      misinterpret the odds of gambling activities, hold false beliefs about skill and
      luck, and over-estimate their subjective chances of success. Accordingly,
      providing accurate information about gambling in venues, or on slot-machines,
      would appear to be a sensible way to enhance the 'safety' of gambling products.
      Unfortunately, such ideas for educating gamblers may be difficult to implement in
      practice because of limitations and conceptual dilemmas in the cognitive
      literature. Irrational beliefs about gambling may be difficult to falsify, are
      often highly idiosyncratic and context-bound, and may stem more from the
      selective misuse of information than from a lack of knowledge about gambling
      activities. Drawing evidence from recent research into gambling-related
      cognitions, this paper examines the key elements of irrational-belief systems,
      and how this work might usefully inform the design of future consumer information
      initiatives.

PMID- 14973396
TI  - Individual, family, and peer correlates of adolescent gambling.
AB  - The primary purpose of this study was to determine the individual, family, and
      peer factors that correlate with adolescent gambling. High school students from
      three states ( N = 1,846) completed an anonymous questionnaire assessing the
      behavior of themselves, their parents, and their peers. Participants also
      reported on their gambling behavior via the SOGS-RA, which was used to create
      five adolescent gambling groups (i.e., Non-Gamblers, Non-Problem Gamblers, At
      Risk Gamblers, Problem Gamblers, and Probable Pathological Gamblers). In a
      discriminant function analysis using demographic, individual, family, and peer
      factors as potential discriminators, two functions emerged that accounted for 94%
      of the variance between groups. The first function was linear, with the Probable
      Pathological Gamblers reporting the highest level of peer and parent gambling,
      susceptibility to peer pressure, conduct problems, binge drinking, suicide
      attempts, drug use, and being male. The second function highlighted three unique
      qualities of individuals in the two outlying groups: Probable Pathological
      Gamblers and Non-Gamblers. These findings suggest that demographic, individual,
      family, and peer variables are all important correlates of probable pathological
      gambling in adolescents. Results also support the utility of a five-group
      classification scheme based on the SOGS-RA. The clinical implications of these
      results are discussed.

PMID- 14973397
TI  - Trajectories of gambling during adolescence.
AB  - This study aimed at empirically identifying groups of adolescents with distinct
      longitudinal trajectories of gambling involvement and validating these groups by
      comparing them with respect to correlates. 903 low SES boys were followed
      annually from age 11 to 16 years. Three groups were found: an early-onset high
      level chronic group, a late-onset high-level group, and a low gambler group. The
      Chronic group and the Low group consistently differed on teacher-rated inhibition
      (i.e., anxiety) during childhood and early adolescence. They also differed on
      concurrent teacher and self ratings of disinhibition (i.e., impulsivity), while
      the Late Onset group appeared to lie in between these groups. Compared to the Low
      group, both high groups subsequently had elevated scores on later gambling
      related problems.

PMID- 14973398
TI  - The relationship between anxiety, smoking, and gambling in electronic gaming
      machine players.
AB  - Given higher reported rates of smoking in populations under treatment for problem
      gambling, in a sample of 81 Electronic Gaming Machine players, this study
      considered whether: 1) there were relationships between tobacco dependency and
      problem gambling, and 2) a common mechanism such as negative affect was involved.
      The untreated sample comprised eighty-one Electronic Gaming Machine players that
      completed the South Oaks Gambling Screen, the Tobacco Dependence Scale and the
      State-Trait Anxiety Inventory. There was a relationship between smoking status
      and scores on the South Oaks Gambling Screen, and negative affect contributed to
      both gambling problems and tobacco dependence. It was suggested that gambling
      problems and tobacco dependence have similar characteristics. The data has
      implications for treatment and anti-smoking legislation in gaming venues.

PMID- 14973399
TI  - Indicated prevention of problem gambling among college students.
AB  - This research provides a brief qualitative description of the development of an
      indicated prevention intervention for college student gamblers. The proposed
      intervention integrates alcohol prevention strategies with elements of gambling
      treatment. The intervention combines cognitive-behavioral skills-training and
      motivational interviewing and includes personalized normative feedback, cognitive
      correction, discussion of gambling consequences, and relapse prevention
      techniques. Examples detailing all phases of the intervention are provided from
      interviews conducted in a pilot of the intervention. Preliminary pilot data
      suggests the intervention shows promise in reducing high risk gambling among
      college students.

PMID- 14973400
TI  - Patterns of autonomic arousal in imaginal situations of winning and losing in
      problem gambling.
AB  - AIMS: To examine changes in skin conductance level (SCL), for problem gamblers in
      response to personally relevant imaginal tasks, representing winning or losing.
      SETTING, DESIGN, PARTICIPANTS AND MEASUREMENTS: SCL and subjective arousal were
      compared for problem poker machine gamblers (n = 13) and a control group (n =
      20). Participants were asked to describe a situation in which they had (a) won
      and (b) lost during a period of gambling. Before and during the task, recordings
      of SCL were taken. FINDINGS: There were significant differences between responses
      of problem and social gamblers. A significant interaction indicated that social
      gamblers became more aroused in reaction to winning than losing, whereas problem
      gamblers became equally aroused in response to both tasks. CONCLUSIONS: The
      results suggest that it may be responses to losing, rather than winning that are
      paramount to the development and maintenance of problem gambling.

PMID- 14973403
TI  - Drugs for intermittent claudication.

PMID- 14973404
TI  - Is Effexor more effective for depression than an SSRI?

PMID- 14973405
TI  - Diagnosis of polycystic ovary syndrome: from NIH criteria to ESHRE-ASRM
      guidelines.
AB  - In the past, the diagnosis of polycystic ovary syndrome (PCOS) was based on
      National Institute of Health (NIH) criteria (hyperandrogenism and chronic
      anovulation) or on sonographic findings of polycystic ovaries. Diffe-rences in
      diagnosis criteria made it difficult to compare the data of studies coming from
      different countries. Moreover, there was criticism of both the methods used. In
      2003, at a joint meeting of the European Society for Human Reproduction (ESHRE)
      and the American Society of Reproductive Medicine (ASRM), new guidelines for the
      diagnosis of PCOS were suggested. According to these guidelines, it is possible
      to reach a diagnosis of PCOS when at least 2 of these 3 elements are present:
      hyperandrogenism, chronic anovulation and polycystic ovaries. New criteria for
      the echographic diagnosis of polycystic ovaries have been suggested, too. These
      diagnostic guidelines represent important progress because they are more flexible
      and permit us to make the diagnosis in patients who were previously excluded by
      the syndrome (such as ovulatory hyperandrogenic women with polycystic ovaries or
      anovulatory normoandrogenic women with polycystic ovaries). However, doubts still
      exist and regard some borderline group of patients such as hirsute ovulatory
      normoandrogenic women with polycystic ovaries. A new classification of PCOS
      syndrome is suggested on the basis of new guidelines.

PMID- 14973406
TI  - [Diagnosis of polycystic ovary syndrome].
AB  - Polycystic ovary syndrome (PCOS) is the most common endocrine disorders among
      women in reproductive age, but diagnostic criteria used in clinical practice are
      still controversial. In 1990 the National Institute of HEALTH (NIH) conference on
      PCOS recommended that diagnostic criteria should include biochemical evidence of
      hyperandrogenism and ovarian dysfunction (in the absence of non-classical adrenal
      hyperplasia) without considering the morphological diagnosis of polycystic ovary
      by ultrasound as an essential part of the diagnosis. In the Rotterdam PCOS
      workshop of May 2003, however, PCOS is diagnosed when 2 of the following criteria
      are recognized: oligomenorrhea and/or anovulation, clinical or biochemical signs
      of hyperandrogenism, ultrasound findings of polycystic ovary. Further-more, it is
      underlined that the metabolic study is not necessary for PCOS diagnosis, while it
      is suggested for "at risk patients" (obesity, diabetes, familiar and obstetrical
      history) with an oral glucose tolerance test (OGTT). A recent study carried out
      by our group underlined the role of ultrasound parameter, in particular
      suggesting a ratio between ovarian stroma area and total area of the ovarian
      section (S/A), with a cut-off of 0.34, as "gold parameter" for PCOS diagnosis,
      because it shows high sensitivity and specificity (96.3%, 97.0% for the S/A).

PMID- 14973407
TI  - The treatment of polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in
      women in reproductive age. As for the treatment of this disease the lack of a
      clear etiology for PCOS has led to a symptom-orientated treatment. However, the
      overall aims of treatment are to induce ovulation for women desiring conception,
      to reduce androgen levels, to reduce body weight and to reduce long-term health
      risks of diabetes mellitus and cardiovascular disease. Clomiphene citrate (CC) is
      recommended as first line treatment for induction of ovulation in patients with
      PCOS by virtue of its efficacy, safety, and ease of administration. Alternatives
      for CC-resistant patients include gonadotrophin therapy (better with low-dose
      step-up protocol) and laparoscopic ovarian diathermy. Recently, recombinant FSH
      (rFSH) has been introduced in clinical practice and it seems more effective than
      urinary FSH as demonstrated by a significantly higher number of follicles
      recruited and embryos obtained with a shorter treatment period. The addition of
      GnRH-agonist to the stimulation protocol for women affected by PCOS could reduce
      premature luteinization and increase cycle fecundity. Other drugs under
      investigation are metformin and cabergoline. Hirsutism is the manifestation of
      hyperandrogenemia in PCOS. The primary goal of the treatment of hirsutim is
      central or peripheral androgen suppression using 3 groups of drugs: inhibitors of
      androgen production (oral contraceptives, GnRH analogues), peripheral androgen
      blockers (cyproterone acetate, flutamide, finasteride and spironolactone), and
      insulin-sensitizing agents (metformin). Weight reduction and exercise could also
      improve not only menstrual disturbances and infertility, but also insulin
      resistance and its adverse metabolic con-sequences.

PMID- 14973408
TI  - Do women with polycystic ovary syndrome have an increased risk of cardiovascular
      disease? Review of the evidence.
AB  - Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder found in
      ~5% of the general population and is characterized by chronic anovulation,
      hyperandrogenism, and insulin resistance. Women with PCOS are at increased risk
      for the development of Type II diabetes and may represent a unique group of women
      at high risk for the development of coronary heart disease (CHD). More adverse
      CHD risk profiles of women with PCOS have been demonstrated in several studies,
      yet actual health outcome studies have been inconclusive as to whether this
      translates into increased rates of cardiovascular disease in PCOS cases when
      compared to controls. This review focuses on the controversy surrounding the
      potential relationship between cardiovascular disease outcomes and polycystic
      ovary syndrome.

PMID- 14973409
TI  - Type 2 diabetes and the polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting women
      in reproductive age, characterized by chronic anovulation and hyperandrogenism.
      The etiology of PCOS is still unknown. However, several studies have suggested
      that insulin resistance plays an important role in the pathogenesis of the
      syndrome. As a consequence of insulin-resistance, women affected by PCOS often
      present abnormalities of glucose metabolism and lipid profile, and have an
      increased risk of type 2 diabetes and cardiovascular disease over-time. Besides
      insulin-resistance, it has been demonstrated that some of these women also have
      alterations in beta-cell-function. Both disorders (insulin-resistance and beta
      cell-dysfunction) are recognized as major risk factors for the development of
      type 2 diabetes. Long-term studies, evaluating the glucose-insulin system in
      women affected by PCOS, have shown a higher incidence of glucose intolerance,
      including both impaired glucose tolerance and type 2 diabetes, compared to age
      and weight matched control populations. The risk of glucose intolerance among
      PCOS subjects seems to be approximately 5 to 10 fold higher than normal and
      appears not limited to a single ethnic group. Moreover, the onset of glucose
      intolerance in PCOS women has been reported to occur at an earlier age than in
      the normal population (approximately by the 3rd-4th decade of life). However,
      other risk factors such as obesity, a positive family history of type 2 diabetes
      and hyperandrogenism may contribute to increasing the diabetes risk in PCOS.

PMID- 14973410
TI  - Polycystic ovary syndrome and type 2 diabetes mellitus.
AB  - Polycystic ovary syndrome (PCOS) is a medical condition that has brought multiple
      specialists together. Gynecologists, endocrinologists, cardiologists,
      pediatricians, and dermatologists are all concerned with PCOS patients and share
      research data and design clinical trials to learn more about the syndrome.
      Insulin resistance is a common feature of PCOS and is more marked in obese women,
      suggesting that PCOS and obesity have a synergistic effect on the magnitude of
      the insulin disorder. It leads to increased insulin secretion by beta-cells and
      compensatory hyperinsulinemia. Hyperinsulinemia associated with insulin
      resistance has been causally linked to all features of the syndrome, such as
      hyperandrogenism, reproductive disorders, acne, hirsutism and metabolic
      disturbances. If beta-cell compensatory response declines, relative or absolute
      insulin insufficiency develops which may lead to glucose intolerance and type 2
      diabetes. Moreover, insulin resistance in PCOS may be considered a risk factor
      for gestational diabetes (GD).

PMID- 14973411
TI  - Metformin for the treatment of the polycystic ovary syndrome.
AB  - The polycystic ovary syndrome (PCOS) is characterized by increased secretion of
      LH, insulin and androgens. The main clinical complaints of women with PCOS
      include: oligo- or amenorrhea, dysfunctional uterine bleeding, hirsutism, obesity
      and/or anovulatory infertility. The first line treatment for these problems
      include: 1) estrogen-progestin therapy for oligomenorrhea and dysfunctional
      uterine bleeding; 2) estrogen-progestin therapy and/or antiandrogens for
      hirsutism; 3) lifestyle changes such as diet and exercise for obesity and 4)
      weight loss or clomiphene for anovulatory infertility. However, clinical trials
      have indicated that metformin is effective second line therapy when first line
      therapy has not been effective, is not acceptable to the patient or is medically
      contraindicated. The addition of metformin to the armamentarium of the
      gynecological endocrinologist represents an important advance.

PMID- 14973412
TI  - Recent advances in the management of women with ovarian cancer.
AB  - Ovarian cancer continues to be the leading cause of death secondary to
      gynecologic cancers among women in the western world. Current treatment of
      ovarian cancer entails a combination of surgery and chemotherapy. Currently, 1st
      line chemotherapy consists of a combination of carboplatin and paclitaxel to
      which approximately 80% of women respond. Women who do not respond to
      chemotherapy or have a recurrence within 6 months of treatment have dismal
      prognoses. Women who respond to chemotherapy usually stay in remission for 1-3
      years and then have tumor recurrence. Women with recurrent ovarian cancer can be
      treated with secondary cytoreduction followed by chemotherapy or by chemotherapy
      alone. Women with recurrent ovarian cancer usually succumb to their disease
      despite occasional good response to chemotherapy. Despite the fact that new
      chemotherapeutic drugs have been found effective among women with ovarian cancer,
      the prognosis of women with the disease continues to be poor. Advances in
      survival will depend on development of more accurate screening techniques and the
      development of new paradigms in treatment.

PMID- 14973413
TI  - [Biologic therapy and epithelial ovarian cancer].
AB  - The identification of new molecular prognostic and predictive factors for ovarian
      cancer may contribute in deciding individual therapeutic strategies; on the other
      hand, there has been growing interest in new biologic therapies to correct
      molecular or genic lesions of neoplastic cells (genic therapy), or to activate
      the specific immune response (immunological therapy). Chemotherapy collateral
      toxic effects, as myelotoxicity, should be reduced through transfection of genes
      that modulate drug resistance in stem cells. The data at present available
      suggest then the potential role of these new treatments, are more specific and
      less toxic than current therapies; however, other biological-molecular studies
      are required to obtain the clinical applications of the results: Aim of this
      study is to provide a review of the most interesting data in ovarian cancer
      biologic therapy.

PMID- 14973414
TI  - The effects of smoking on estradiol metabolism.
AB  - Smoking remains a major health problem especially among women and it influences
      estrogen metabolism and the risk for multiple estrogen sensitive outcomes. Many
      indirect effects of smoking exist through the ability of the by-products to
      modify a variety of drugs, enzymes, and hormones. The results of several in vitro
      studies have shown that constituents of cigarette smoke have significant effects
      on production and metabolism of estrogens. In some cases, such as osteoporosis
      and endometrial cancer, smoking appears to attenuate the effects of estrogen.
      However, for other outcomes such as breast cancer, venous thromboembolic events
      (VTE), and coronary heart disease (CHD), the relationship between smoking and
      estrogen exposure is less defined. Based on the preponderance of evidence,
      smokers are likely to require higher doses of hormone replacement therapy (HRT)
      to achieve comparable clinical effect to that observed in nonsmokers. However,
      uptitrating the dose of HRT in smokers to achieve a desired systemic level or
      clinical response may simultaneously increase risk for adverse effects that are
      primarily driven by hepatic rather than systemic exposure. The healthy benefits
      from smoking cessation should be expressed to women who choose to use HRT, and
      every effort should be made to encourage them to stop smoking so that they can be
      effectively treated with the lowest possible dose of HRT.

PMID- 14973415
TI  - Radiolabelling of peptides for diagnosis and therapy of non-oncological diseases.
AB  - Radiolabelled peptides have significant potential as radiopharmaceuticals for the
      diagnosis and therapy of receptor-expressing diseases. Methods have been
      developed for labelling peptides with a variety of radionuclides having a broad
      range of chemical and physical properties. These methods include both direct
      (where the radionuclide is bound directly to one or more atoms of the peptide
      structure) and indirect techniques in which bifunctional coupling agents are
      employed. Although most commonly applied to date in the field of oncology, a
      significant number of applications in non-oncological diseases have also been
      proposed and these can be expected to expand as the technology progresses. An
      overview is presented of some peptide-receptor systems in radiopharmaceutical
      development and the techniques which have been employed to radiolabel these
      peptides with isotopes of iodine, yttrium, indium, gallium, copper and
      technetium. While many of the examples employed are derived from cancer related
      indications, identical radiopharmaceutical chemistry can also be applied to
      peptides with applications in the fields of immunology, infection and other
      inflammatory conditions.

PMID- 14973416
TI  - 99mTc-antimicrobial peptides: promising candidates for infection imaging.
AB  - This review presents the state of the art of imaging of bacterial and fungal
      infections in laboratory animals using antimicrobial peptides labelled with
      technetium-99m ((99m)Tc). The mechanistic basis of this approach is that these
      peptides accumulate at sites of infection, but not in sterile inflammatory
      lesions, because of their preferential binding to bacteria and fungi over
      mammalian cells. For practical reasons, such as production of large amounts of
      peptides under good laboratory practice conditions and favourable
      pharmacokinetics, synthetic peptides representing such binding domains of natural
      antimicrobial peptides are preferred. On the basis of their preferential in vitro
      and in vivo binding to microorganisms over human cells, fast and easy penetration
      into the target area, and rapid clearance from the circulation via the urinary
      tract, various (99m)Tc-antimicrobial peptides were identified. Next, it was
      determined whether these radiopharmaceuticals distinguish infectious foci from
      sites of sterile inflammation. Further experiments with (99m)Tc-ubiquicidin
      derived peptides in infected laboratory animals have revealed that the
      radioactivity at the infectious site correlated well with the number of viable
      bacteria present, indicating that these (99m)Tc-labelled peptides may enable the
      monitoring of the efficacy of antimicrobial therapy. Together, (99m)Tc-labelled
      synthetic peptides derived from human ubiquicidin are promising candidates for
      imaging of bacterial and fungal infections in nuclear medicine.

PMID- 14973417
TI  - Radiolabeled chemotactic cytokines: new agents for scintigraphic imaging of
      infection and inflammation.
AB  - Several radiopharmaceuticals are currently used for diagnosis of inflammatory and
      infectious diseases in patients. Most inflammatory and infectious processes can
      be visualized with radiolabeled autologous leukocytes, currently considered to be
      the most appropriate radiopharmaceutical for this purpose. This agent is very
      well capable to delineate most inflammatory and infectious foci in a relatively
      short time after injection. The time-consuming and intricate labeling procedure
      and the handling of potentially contaminated blood, however cause that there is a
      great interest in the development of new radiopharmaceuticals comprising the same
      imaging qualities but without these disadvantages. Besides radiolabeled
      leukocytes several other radiopharmaceuticals, such as (67)Ga-citrate,
      radiolabeled anti-granulocyte antibodies and FDG are used to image infection and
      inflammation. These agents accumulate in infectious and inflammatory lesions in a
      non-specific manner or have suboptimal diagnostic characteristics. Nowadays,
      there is a great interest in the development of radiolabeled chemotactic and
      chemokinetic cytokines that accumulate and are retained in infectious and
      inflammatory foci by specific interaction with infiltrated inflammatory cells. In
      this review we describe the specific characteristics of the chemotactic and
      chemokinetic compounds that are currently studied as potential
      radiopharmaceutical to visualize infectious and inflammatory foci. The
      characteristics of a series of cytokines (IL-1, IL-2), chemokines (IL-8, PF-4,
      MCP-1, NAP-2), complement factors (C5a, C5adR), chemotactic peptides (fMLF) and
      other chemotactic factors (LTB4) are described. The potentials of these compounds
      to serve as an imaging agent are discussed.

PMID- 14973418
TI  - The developing role of peptide radiopharmaceuticals in the study of chronic
      inflammation: new techniques for novel therapeutic options.
AB  - Chronic inflammatory diseases usually lead to fibrosis of the target organ and
      consequent hypo function. They are often relapsing, invalidating and require life
      long treatment. In this class of patients it is very important to try and achieve
      specific immune suppression to extinguish the immune process with the aim of
      preventing the disease, preventing or delaying complications and avoiding disease
      relapse, often requiring surgical intervention. It is important that, while
      attempting to improve the quality of life of these patients by means of anti
      inflammatory drugs, side effects are reduced to a minimum via the use of specific
      immune therapies that block as selectively as possible the pathologic mechanism
      responsible for the disease. New therapeutic options are being developed for
      specific targeted therapies. Several trials are being performed to assess the
      efficacy and safety of this approach. All of them, however, rely on the clinical
      assessment of the patients to evaluate the effect of treatment. It would be
      important to use an objective and reliable method to highlight directly the
      immune process underlying the individual disease. This manuscript reviews the
      radiopharmaceuticals available or recently developed for imaging chronic
      inflammatory diseases and their use for therapy decision making and follow-up.

PMID- 14973419
TI  - The role of octreotide scintigraphy in rheumatoid arthritis and sarcoidosis.
AB  - Somatostatin receptors are widely expressed on cells and tissues throughout the
      human body. Apart from their expression in the physiological target organs of the
      peptide, somatostatin receptors are also expressed in various tumours. The
      expression of somatostatin receptors on neuroendocrine tumours led to the
      development of somatostatin receptor scintigraphy using [(111)In-DTPA-D-Phe(1)]
      octreotide ((111)In-pentetreotide) in order to visualize somatostatin receptor
      positive tumours and their metastases in vivo. Previous studies reported the
      expression of somatostatin receptors in both normal and pathological cells and
      tissues of the human immune system as well. Somatostatin receptors have been
      demonstrated in Hodgkin's and non-Hodgkin's lymphomas and sst scintigraphy has
      shown to be a useful tool in diagnosis and staging of these diseases. Moreover,
      sst expression has also been detected in granulomateus diseases, like sarcoidosis
      and auto-immune diseases, like rheumatoid arthritis. In this paper we discuss the
      (possible) role of somatostatin receptor scintigraphy in diagnosis, staging or
      follow-up of patients suffering from sarcoidosis and rheumatoid arthritis.

PMID- 14973420
TI  - Non-oncologic applications of radiolabeled peptides in nuclear medicine.
AB  - Radiolabeled peptides have been investigated for diagnostic imaging in a variety
      of non-oncologic diseases. For imaging thromboembolic disease, peptides which
      bind to various components of thrombi have been tested. For targeting the fibrin
      component of thrombi, peptide analogues of fibrin or fragments of fibronectin
      which have a distinct binding domain for fibrin have been studied. For targeting
      activated platelets within thrombi, linear and cyclic peptide antagonists of the
      glycoprotein IIb/IIIa receptor on platelets have been studied, as well as
      naturally occurring antagonists of this receptor which are found in venoms.
      Analogues of laminin and thrombospondin which bind to other receptors on
      platelets have also been tested. There is an approach which uses a peptide to
      target thrombin which is sequestered within a fibrin clot. Another area of
      investigation has been to develop an improved radiopharmaceutical for imaging
      sites of infection and/or inflammation. Peptides which would bind to leukocytes
      in vivo, such as antagonists to the tuftsin receptor, chemotactic peptides,
      interleukin-8, or a platelet factor 4 analogue, have been radiolabeled for this
      purpose. These agents would enable imaging of both infection and inflammation.
      Development of a radiopharmaceutical for specifically imaging infection has
      focused on antimicrobial peptides such as human neutrophil defensin, ubiquicidin,
      human lactoferrin and alafosfalin, which are expected to bind selectively to
      microorganisms and not to leukocytes. Radiolabeled peptides are also being
      explored as agents for assessing unstable atherosclerotic plaque (endothelin),
      amyloid deposits (amyloid beta peptides), and the consequences of diabetes
      mellitus (human C-peptide).

PMID- 14973421
TI  - "Pathophysiologic mapping" of venous thromboembolism: opportunities for
      radiolabeled peptides.
AB  - The serious clinical and economic impact of venous thromboembolic (VTE) disease
      is undisputed. What concerns practitioners and researchers alike is the seeming
      inability to truly mitigate the ramifications of VTE. Ironically, the current
      approaches to the diagnostic evaluation of suspected VTE patients tends to favor
      the application of anatomic modalities, which by virtue of their principles of
      detection, seemingly ignore the extensive knowledge base of VTE pathophysiology
      and natural history. In other words, are we seeking the appropriate types of
      information in patients with suspected VTE? Research in nuclear medicine
      techniques for detecting VTE began approximately 25 years ago. Recently, the
      emergence of the radiolabeled peptides as a clinically applicable technology
      platform has encouraged a different way of evaluating VTE. Many radiolabeled
      peptide candidates are undergoing preclinical and clinical research. Currently,
      only one, (99m)Tc-apcitide (AcuTect), has been approved (since 1998) for clinical
      use, specifically in the United States. Its availability this time has fueled
      ongoing clinical research to further elucidate the benefits of this unique
      peptide technology. Consequently, significant insight has been gained from large
      prospective clinical trials. Furthermore, this insight has kindled increasing
      interest in (99m)Tc-apcitide and potential new entrants into this special
      "diagnostic class". Unlike the more popular modalities, radiolabeled peptides
      circumvent many of the clinical and anatomic challenges to objectively and
      accurately diagnosing VTE. The importance of an objective and accurate diagnosis
      is understood, because it is paramount to a cost-effective treatment strategy. In
      addition to describing the current activities concerning the development for and
      use of radiolabeled peptides for clinical practice, this manuscript is intended
      to promulgate a thought-provoking argument for changing our current approach to
      the diagnostic evaluation of VTE. Despite technological and medical advances, we
      continue to debate controversial issues in VTE, which seemingly and arguably
      disproportionately, focus on treatment (i.e., who?, when?, how much? and for how
      long?). Should we not adopt a more robust approach to VTE problem-solving, which
      would logically start with the diagnosis? Perhaps the validated and perceived
      advantages of the radiolabeled peptides are all the rationale we need to advance
      beyond the status quo? Only time and continued research will tell.

PMID- 14973422
TI  - Radiolabelled peptides and low molecular weight proteins in metabolic diseases.
AB  - During the last decade there has been a tremendous effort to develop labelled
      peptides for diagnosis and therapy. The main goal has been to develop tumor
      imaging/therapeutic agents, as well as peptides directed to the study of
      thrombosis and infection. Relatively few efforts have been made to develop
      peptides directed to the study of metabolic diseases. Ideally, a peptide suitable
      for the study of metabolism should be constructed keeping in mind the following
      characteristics: a) preserved affinity constant, b) preserved or improved
      specificity for its binding site, c) increased biological half-life in comparison
      with the parent peptide, d) labelling with a g or positron emitter whose physical
      half-life fits with the biological half-life, e) strong binding of the nuclide to
      the molecule so that it cannot be released after internalization. In this paper
      some of the peptides or low molecular weight proteins along with some analogues
      which have been employed in experimental studies and in humans are reviewed, with
      major emphasis on amyloid seekers, insulin and leptin. Many of these
      radiopharmaceuticals have been labelled with iodine isotopes, however their in
      vivo application suffer of severe limitations due to rapid release of iodine
      after internalization. On the other hand, new perspectives are opened by new
      radiofluorination techniques, which offer the unique advantage to quantify organ
      uptake and kinetics, parameters which are of paramount importance in metabolic
      studies.

PMID- 14973423
TI  - Imaging cell death in vivo.
AB  - A technique to image programmed cell death would be useful both in clinical care
      and in drug development. The most widely studied agent for the in vivo study of
      apoptosis is radiolabeled annexin V, an endogenous protein labeled with
      technectium-99m, now undergoing clinical trials in both Europe and the United
      States. While annexin V has been studied extensively in humans the precise
      mechanism(s) of uptake this agent in vivo is unclear and needs further study.
      Other agents are also under development, including radiolabeled forms of Z
      VAD.fmk, a potent inhibitor of the enzymatic cascade intimately associated with
      apoptosis. In addition other technologies, such as diffusion weighted magnetic
      resonance imaging and magnetic resonance imaging with contrast agents, such as
      small paramagnetic iron oxide particles coated with peptides have also been
      advocated as methods to monitor apoptotic cell death. The potential applications
      of imaging apoptosis as a marker of early response to therapy in cancer, acute
      cerebral and myocardial ischemic injury and infarction, immune mediated
      inflammatory disease and transplant rejection are reviewed.

PMID- 14973424
TI  - The role of labeled Annexin A5 in imaging of programmed cell death. From animal
      to clinical imaging.
AB  - Programmed cell death plays a critical role in embryology, homeostasis and
      disease. However, until recently no non-invasive imaging modality has been able
      to visualize this process directly. Annexin A5 binds to cells undergoing
      programmed cell death. When labeling this protein, Annexin A5 becomes a tool for
      the detection of programmed cell death in vitro and in vivo. Labeled Annexin A5
      has enabled our group and others to detect programmed cell death non-invasively
      in animals and patients. This review will highlight the development of this
      imaging modality in cellular and animal models. Furthermore, we will discuss
      Annexin A5 imaging in human disease. We will focus on the clinical applications
      and their relevance, limitations and future perspectives of non-invasive imaging
      of programmed cell death using labeled Annexin A5.

PMID- 14973425
TI  - [Diagnosis of hereditary neuropathies in adult-subjects].
AB  - The clinical approach to hereditary neuropathies of adulthood has become very
      complex. The following issues are reviewed: elements that point to a neuropathy
      of inherited origin, different modalities of presentation, laboratory and
      instrumental diagnostic tests, including molecular tests, symptoms and signs of
      involvement of other organs. It is useful to identify different phenotypes
      according to: disease course; involvement of motor, sensory, autonomic fibres;
      site of lesion (neuropathy versus neuronopathy); calibre of involved fibres
      (small-fibre versus large-fibre neuropathy); presence of distinctive symptoms
      (neuropathic pain); involvement of other organs or apparatus. Charcot-Marie-Tooth
      (CMT) disease, familial amyloid polyneuropathy (FAP), hereditary sensory and
      autonomic neuropathy, Fabry disease, Tangier disease, porphyric neuropathies,
      Refsum disease, hereditary neuropathy with liability to pressure palsies (HNPP),
      hereditary neuralgic amyotrophy and other rare disorders involving the peripheral
      nervous system are reviewed.

PMID- 14973426
TI  - Thyroglobulin: current aspects of its role in autoimmune thyroid disease and
      thyroid cancer.
AB  - Thyroglobulin (Tg) is a large glycoprotein (molecular weight: 660000) with 2
      polypeptide chains of approximately 2768 amino acids each. It functions both as a
      pro-hormone and storage hormone for thyroid hormones. The complete Tg gene
      sequence has been determined for human, rat and bovine species. Tg is one of the
      thyroid autoantigens recognised in patients with autoimmune thyroid disease
      (AITD). Antibodies to Tg (TgAb) are present in the serum of patients with AITD
      and are also sometimes present in healthy euthyroid subjects. Though at least 40
      antigenic epitopes on human Tg have been identified, only 2 or 3 of these bind
      TgAb. Epitope mapping studies suggest that TgAb in AITD patients express a
      restricted binding pattern while TgAb in the serum of healthy individuals do not
      show such specific binding. There is evidence to suggest that iodination of Tg
      may alter these epitope binding patterns. TgAb IgG on the other hand, do not
      appear to be subclass restricted. Several Tg fragments capable of inducing a T
      cell response have been described. Tg is routinely used in the postoperative
      monitoring of patients with differentiated thyroid cancer. Its use has been
      limited by problems with assay methods which include poor inter-laboratory
      standardisation, poor inter-assay variation, low functional sensitivity of the
      assays, hook effects, and interference from TgAb present in patients serum. The
      use of rh-TSH in stimulating Tg prior to testing has improved the sensitivity of
      Tg values in the suppressed state.

PMID- 14973427
TI  - Direct or reverse correlations within the expression of activation,
      differentiation or T-B cooperation molecules on chronic lymphocytic leukemia B
      cells.
AB  - AIM: B-cell chronic lymphocytic leukemia (B-CLL) is characterized by homogeneous
      coexpression of CD19, CD23 and CD5, and poor expression of membrane Ig. The aim
      of this study was to evaluate, in B-CLL patients and in healthy subjects by flow
      cytometry, B cell expression of surface molecules involved in cell activation,
      differentiation, T-B cooperation and apoptosis. METHODS: The study population
      consisted of 29 patients (16 men and 13 women; mean age: 66.5 years) with B-CCL.
      The control group consisted of 16 sex- and age-matched healthy subjects. The
      results are reported as percentages and mean fluorescence intensity (MFI) of
      CD19+ cells coexpressing each analyzed molecule. RESULTS: We found that the
      lymphocyte activation markers, CD69, CD25 and CD11c, were more expressed in B-CLL
      patients than controls. CD38 and CD95 expressions were higher on normal B
      lymphocytes than leukemic B cells. Finally, CD80 and CD86, molecules involved in
      T-B cooperation, showed an inverse expression between lymphocytes of B-CLL
      patients and healthy subjects. CD80 was higher on normal than leukemic B cells,
      while CD86 expression was higher on CLL B cells. Linear regression analysis
      showed a positive correlation between CD80 and CD95 expression on leukemic B
      cells; a reverse correlation was observed between CD69 and CD11c. CONCLUSION:
      These results suggest that common mechanisms may regulate the simultaneous
      expression of CD80 and CD95 or the reverse expression of CD69 and CD11c,
      respectively, in different stages of B cell activation and/or differentiation.

PMID- 14973428
TI  - FasL and Bax genes are differentially expressed in acinar epithelium and
      inflammatory cells of primary Sjogren salivary glands.
AB  - AIM: Assess the expression of FasL, Bax, TNFa and IL-6, genes in salivary glands
      of primary Sjogren patients. METHODS: Twenty minor salivary glands from patients
      with primary Sjogren syndrome were studied by in situ hybridization with cDNA
      fluorescent probes. An equal number of control biopsies were included. RESULTS:
      Sjogren salivary glands differentially display the inflammatory cytokines and pro
      apoptotic mRNAs as follows: mononuclear infiltrating cells exhibited IL-6 and
      TNFa, whereas the ductal epithelium and acinary cells mainly expressed FasL and
      Bax. Control biopsies were negative. CONCLUSION: Present data suggest that local
      production of inflammatory cytokines would induce the Fas and Bax pathways
      committing the ductal epithelium and the acinary cells to apoptosis.

PMID- 14973429
TI  - [Emergency department ultrasonography: impact on patient management and cost
      effectiveness].
AB  - AIM: Ultrasonography is the most common noninvasive method for the evaluation of
      body organs and systems. However, the feasibility and potential advantages of
      ultrasound scanning by emergency physicians have not yet been fully explored. We
      therefore wanted to determine the impact of ultrasound scanning by emergency
      physicians on patient management in the Emergency Department, length of hospital
      stay, and related costs. METHODS: From a data-base search at our hospital we
      selected 111 patients and divided them into 3 groups according to symptoms: right
      hypochondriac region pain (Group A), flank pain (Group B), abdominal pain and
      hemodynamic instability (Group C). Patients were further stratified into 3
      subgroups according to whether they were treated by an emergency physician or a
      radiologist or did not undergo ultrasonography. For each group the mean length of
      stay in the emergency department, the complications rate, the recurrence rate
      (defined as return visit to the emergency department for the same pathology) and
      the related costs were calculated. RESULTS: Of the 111 patients, 76 received
      ultrasound scanning, of which 43 were treated by an emergency physician. The
      length of hospital stay for this group was shorter than that of the other 2
      subgroups. The recurrence rate was highest in the group that did not undergo
      ultrasonography. The costs were lower for the group that received ultrasound
      scanning by an emergency physician than for the group treated by a radiologist
      (Euro 20 vs Euro 38). CONCLUSION: Ultrasound scanning by emergency physicians can
      shorten length of hospital stay for emergency patients, reduce recurrence rates
      for the same pathology and lower patient management costs.

PMID- 14973430
TI  - Efficacy of disodium-clodronate in the management of joint pain in rheumatoid
      arthritis. Six months open study.
AB  - AIM: The aim of the study was to evaluate the effect on the articular pain of 100
      mg of disodium-clodronate administered for 6 days a week by intramuscular
      injection in rheumatoid arthritis (RA) patients. METHODS: We studied 46 patients
      (38 females and 8 males middle age 57+/-6.2 years, range from 30 to 80 years)
      with established RA, in the II and III anatomical stage according to
      Steinbrocker. Therapeutic regimen was for all patients oral methotrexate 7.5 mg
      weekly, prednisone 7.5 mg/day and AINS. All of these patients also received
      disodium-clodronate 100 mg for 6 days a week for 6 months. The results of the VAS
      for pain, the patient global assessment and the physician global assessment on
      disease activity have been recorded at baseline, at the 2 months and at 6 months
      of therapy. RESULTS: VAS for pain and patient global assessment of disease
      activity values decreased significantly after 2 months of therapy (p<0.01) and in
      comparing basal versus final observation, but they did not change significantly
      from month 2 to month 6. The score of physician global assessment on disease
      activity was found to be significantly improved comparing the basal versus 2
      months observation, and 2 months versus 6 months observations (p<0.01).
      CONCLUSION: Disodium-clodronate may be considered an adjunctive therapy in the
      pain management of RA patients.

PMID- 14973431
TI  - Treatment of Whipple disease.

PMID- 14973432
TI  - Acetaldehyde increases dopaminergic neuronal activity in the VTA.
AB  - Acetaldehyde is the first and principal metabolite of ethanol administered
      systemically. To its rise in blood, after administration of disulfiram, is
      ascribed the aversive reaction that should discourage alcoholics from drinking.
      In the present study, we sought to determine the effect of acetaldehyde on the
      electrophysiological properties of dopamine (DA)-containing neurons in the ventro
      tegmental area (VTA) of rats in vivo. Intravenous (i.v.) administration of
      acetaldehyde (5-40 mg/kg) readily and dose-dependently increased the firing rate,
      spikes/burst, and burst firing of VTA neurons. Ethanol (250-1000 mg/kg/i.v.)
      administration produced similar increments in electrophysiological parameters. In
      addition, a second group of rats was pretreated with the alcohol-dehydrogenase
      inhibitor 4-methyl-pyrazole (90 mg/kg) intraperitoneally (i.p.), and ethanol and
      acetaldehyde were administered i.v. at the same doses, 48 h later. In this group,
      ethanol effects were drastically reduced and the firing rate, spikes/burst, and
      burst firing were not significantly altered. In contrast, acetaldehyde fully
      retained its capacity to stimulate electrophysiological indices. The results
      indicate that acetaldehyde produces electrophysiological actions on VTA neurons
      in vivo, similar to those produced by ethanol, and significantly participate in
      ethanol-induced increment in DA neuronal activity. These results also suggest
      that acetaldehyde, by increasing DA neuronal activity in the VTA, may
      significantly contribute to the centrally mediated positive motivational
      properties of ethanol, which would oppose the well-known peripherally originating
      aversive properties.

PMID- 14973433
TI  - Unbalanced statistical analysis of combined divalproex and antipsychotic therapy
      for schizophrenia.

PMID- 14973435
TI  - Family psychopathology and magnitude of reductions in occipital cortex GABA
      levels in panic disorder.

PMID- 14973436
TI  - Viral-induced T helper type 1 responses enhance allergic disease by effects on
      lung dendritic cells.
AB  - It is widely accepted that T helper type 1 (T(H)1) cytokines such as interferon
      gamma (IFN-gamma) antagonize allergic diseases mediated by T(H)2 cytokines. The
      'hygiene hypothesis' has also proposed that decreased childhood exposure to
      pathogen-derived T(H)1 cytokines may underlie the recent increased prevalence of
      asthma, a T(H)2-mediated disease. We show here that influenza A viral infection,
      which induces large amounts of intrapulmonary IFN-gamma production, unexpectedly
      enhanced later allergen-specific asthma and promoted dual allergen-specific T(H)1
      and T(H)2 responses. Pulmonary dendritic cells obtained from the lung after viral
      clearance and resolution of acute inflammation conferred enhanced allergic
      disease and concurrent T(H)1 and T(H)2 immune responses, and these effects were
      dependent on IFN-gamma secreted during the acute viral infection. Thus,
      respiratory viral infection and the acute T(H)1 response can positively regulate
      T(H)2-dependent allergic pulmonary disease in vivo, at least in part, by altering
      pulmonary dendritic cell function.

PMID- 14973437
TI  - Cis association of Ly49A with MHC class I restricts natural killer cell
      inhibition.
AB  - Natural killer (NK) cell function is negatively regulated by inhibitory receptors
      interacting with major histocompatibility complex class I molecules expressed on
      target cells. Here we show that the inhibitory Ly49A NK cell receptor not only
      binds to its H-2D(d) ligand expressed on potential target cells (in trans) but
      also is constitutively associated with H-2D(d) in cis (on the same cell). Cis
      association and trans interaction occur through the same binding site.
      Consequently, cis association restricts the number of Ly49A receptors available
      for binding of H-2D(d) on target cells and reduces NK cell inhibition through
      Ly49A. By lowering the threshold at which NK cell activation exceeds NK cell
      inhibition, cis interaction allows optimal discrimination of normal and abnormal
      host cells.

PMID- 14973438
TI  - Calcineurin imposes T cell unresponsiveness through targeted proteolysis of
      signaling proteins.
AB  - Sustained calcium signaling induces a state of anergy or antigen unresponsiveness
      in T cells, mediated through calcineurin and the transcription factor NFAT. We
      show here that Ca(2+)-induced anergy is a multistep program that is implemented
      at least partly through proteolytic degradation of specific signaling proteins.
      Calcineurin increased mRNA and protein of the E3 ubiquitin ligases Itch, Cbl-b
      and GRAIL and induced expression of Tsg101, the ubiquitin-binding component of
      the ESCRT-1 endosomal sorting complex. Subsequent stimulation or homotypic cell
      adhesion promoted membrane translocation of Itch and the related protein Nedd4,
      resulting in degradation of two key signaling proteins, PKC-theta and PLC-gamma1.
      T cells from Itch- and Cbl-b-deficient mice were resistant to anergy induction.
      Anergic T cells showed impaired calcium mobilization after TCR triggering and
      were unable to maintain a mature immunological synapse, instead showing late
      disorganization of the outer ring containing lymphocyte function-associated
      antigen 1. Our results define a complex molecular program that links gene
      transcription induced by calcium and calcineurin to a paradoxical impairment of
      signal transduction in anergic T cells.

PMID- 14973439
TI  - Leapfrogging the power grid.

PMID- 14973440
TI  - Publishers split over response to US trade embargo ruling.

PMID- 14973441
TI  - Scientists slam Bush record.

PMID- 14973442
TI  - Guatemalan forensic work brings award and death threats.

PMID- 14973443
TI  - Cloning success marks Asian nations as scientific tigers.

PMID- 14973444
TI  - Colwell calls time on 'wonderful run' at NSF.

PMID- 14973445
TI  - Medical research wins simpler grants and extra cash.

PMID- 14973446
TI  - Berlin biologists outraged by imminent pay cut.

PMID- 14973448
TI  - NASA casts a shadow over bid to illuminate dark energy.

PMID- 14973447
TI  - Misconduct row fuels calls for reform.

PMID- 14973449
TI  - Thumbs up for fresh formula to gauge university funding.

PMID- 14973451
TI  - Science at the movies: the fabulous fish guy.

PMID- 14973452
TI  - Origins of life: born in a watery commune.

PMID- 14973453
TI  - Learning humility from a Nobel prizewinner.

PMID- 14973454
TI  - Dropping habilitation would aid progress in Poland.

PMID- 14973455
TI  - Polish journals have an international impact.

PMID- 14973460
TI  - One more thing...

PMID- 14973461
TI  - Neuroscience: immigration denied.

PMID- 14973462
TI  - Palaeoclimate: low-down on a rhythmic high.

PMID- 14973463
TI  - Transcription: origins of licensing control.

PMID- 14973464
TI  - Particle physics: two is the magic number.

PMID- 14973466
TI  - Malaria: a changed climate in Africa?

PMID- 14973467
TI  - Materials science: give a shell a break.

PMID- 14973468
TI  - Superconductivity: shine a light.

PMID- 14973470
TI  - Pathology: cancer cells compress intratumour vessels.
AB  - The delivery of therapeutic drugs to solid tumours may be impaired by structural
      and functional abnormalities in blood and lymphatic vessels. Here we provide
      evidence that proliferating cancer cells cause intratumour vessels to compress
      and collapse. By reducing this compressive mechanical force and opening vessels,
      cytotoxic cancer treatments have the potential to increase blood perfusion,
      thereby improving drug delivery.

PMID- 14973471
TI  - Neutral theory: the stability of forest biodiversity.
AB  - The unified neutral theory of biodiversity and biogeography provides a dynamic
      null hypothesis for the assembly of natural communities. It is also useful for
      understanding the influence of speciation, extinction, dispersal and ecological
      drift on patterns of relative species abundance, species-area relationships and
      phylogeny. Clark and McLachlan argue that neutral drift is inconsistent with the
      palaeorecord of stability in fossil pollen assemblages of the Holocene forests of
      southern Canada. We show here that their analysis is based on a partial
      misunderstanding of neutral theory and that their data alone cannot unambiguously
      test its validity.

PMID- 14973473
TI  - Ecology: living in synchrony on Greenland coasts?
AB  - Theory indicates that correlated weather may synchronize populations, but the
      extent to which this holds for non-identical, nonlinear systems is uncertain.
      Post and Forchhammer claim to have shown climate-induced synchrony for musk oxen
      and caribou that are separated by the Greenland ice sheet. However, logical and
      mathematical errors undermine their finding. Whether or not large-scale weather
      can be a major synchronizing factor across species remains an open question.

PMID- 14973476
TI  - Grain boundaries as reservoirs of incompatible elements in the Earth's mantle.
AB  - The concentrations and locations of elements that strongly partition into the
      fluid phase in rocks provide essential constraints on geochemical and
      geodynamical processes in Earth's interior. A fundamental question remains,
      however, as to where these incompatible elements reside before formation of the
      fluid phase. Here we show that partitioning of calcium between the grain
      interiors and grain boundaries of olivine in natural and synthetic olivine-rich
      aggregates follows a thermodynamic model for equilibrium grain-boundary
      segregation. The model predicts that grain boundaries can be the primary storage
      sites for elements with large ionic radius--that is, incompatible elements in the
      Earth's mantle. This observation provides a mechanism for the selective
      extraction of these elements and gives a framework for interpreting geochemical
      signatures in mantle rocks.

PMID- 14973477
TI  - Whisker movements evoked by stimulation of single pyramidal cells in rat motor
      cortex.
AB  - Neuronal activity in the motor cortex is understood to be correlated with
      movements, but the impact of action potentials (APs) in single cortical neurons
      on the generation of movement has not been fully determined. Here we show that
      trains of APs in single pyramidal cells of rat motor cortex can evoke long
      sequences of small whisker movements. For layer-5 pyramids, we find that evoked
      rhythmic movements have a constant phase relative to the AP train, indicating
      that single layer-5 pyramids can reset the rhythm of whisker movements. Action
      potentials evoked in layer-6 pyramids can generate bursts of rhythmic whisking,
      with a variable phase of movements relative to the AP train. An increasing number
      of APs decreases the latency to onset of movement, whereas AP frequency
      determines movement direction and amplitude. We find that the efficacy of
      cortical APs in evoking whisker movements is not dependent on background cortical
      activity and is greatly enhanced in waking rats. We conclude that in vibrissae
      motor cortex sparse AP activity can evoke movements.

PMID- 14973478
TI  - Decoherence of matter waves by thermal emission of radiation.
AB  - Emergent quantum technologies have led to increasing interest in decoherence--the
      processes that limit the appearance of quantum effects and turn them into
      classical phenomena. One important cause of decoherence is the interaction of a
      quantum system with its environment, which 'entangles' the two and distributes
      the quantum coherence over so many degrees of freedom as to render it
      unobservable. Decoherence theory has been complemented by experiments using
      matter waves coupled to external photons or molecules, and by investigations
      using coherent photon states, trapped ions and electron interferometers. Large
      molecules are particularly suitable for the investigation of the quantum
      classical transition because they can store much energy in numerous internal
      degrees of freedom; the internal energy can be converted into thermal radiation
      and thus induce decoherence. Here we report matter wave interferometer
      experiments in which C70 molecules lose their quantum behaviour by thermal
      emission of radiation. We find good quantitative agreement between our
      experimental observations and microscopic decoherence theory. Decoherence by
      emission of thermal radiation is a general mechanism that should be relevant to
      all macroscopic bodies.

PMID- 14973479
TI  - High-transition-temperature superconductivity in the absence of the magnetic
      resonance mode.
AB  - The fundamental mechanism that gives rise to high-transition-temperature (high
      T(c)) superconductivity in the copper oxide materials has been debated since the
      discovery of the phenomenon. Recent work has focused on a sharp 'kink' in the
      kinetic energy spectra of the electrons as a possible signature of the force that
      creates the superconducting state. The kink has been related to a magnetic
      resonance and also to phonons. Here we report that infrared spectra of
      Bi2Sr2CaCu2O8+delta (Bi-2212), shows that this sharp feature can be separated
      from a broad background and, interestingly, weakens with doping before
      disappearing completely at a critical doping level of 0.23 holes per copper atom.
      Superconductivity is still strong in terms of the transition temperature at this
      doping (T(c) approximately 55 K), so our results rule out both the magnetic
      resonance peak and phonons as the principal cause of high-T(c) superconductivity.
      The broad background, on the other hand, is a universal property of the copper
      oxygen plane and provides a good candidate signature of the 'glue' that binds the
      electrons.

PMID- 14973480
TI  - Clarifying the glass-transition behaviour of water by comparison with
      hyperquenched inorganic glasses.
AB  - The formation of glasses is normal for substances that remain liquid over a wide
      temperature range (the 'good glassformers') and can be induced for most liquids
      if cooling is fast enough to bypass crystallization. During reheating but still
      below the melting point, good glassformers exhibit glass transitions as they
      abruptly transform into supercooled liquids, whereas other substances transform
      directly from the glassy to the crystalline state. Whether water exhibits a glass
      transition before crystallization has been much debated over five decades. For
      the last 20 years, the existence of a glass transition at 136 K (ref. 3) has been
      widely accepted, but the transition exhibits qualities difficult to reconcile
      with our current knowledge of glass transitions. Here we report detailed
      calorimetric characterizations of hyperquenched inorganic glasses that, when
      heated, do not crystallize before reaching their glass transition temperatures.
      We compare our results to the behaviour of glassy water and find that small
      endothermic effects, such as the one attributed to the glass transition of water,
      are only a 'shadow' of the real glass transition occurring at higher
      temperatures, thus substantiating the conclusion that the glass transition of
      water cannot be probed directly.

PMID- 14973481
TI  - High-latitude influence on the eastern equatorial Pacific climate in the early
      Pleistocene epoch.
AB  - Many records of tropical sea surface temperature and marine productivity exhibit
      cycles of 23 kyr (orbital precession) and 100 kyr during the past 0.5 Myr (refs 1
      5), whereas high-latitude sea surface temperature records display much more
      pronounced obliquity cycles at a period of about 41 kyr (ref. 6). Little is
      known, however, about tropical climate variability before the mid-Pleistocene
      transition about 900 kyr ago, which marks the change from a climate dominated by
      41-kyr cycles (when ice-age cycles and high-latitude sea surface temperature
      variations were dictated by changes in the Earth's obliquity) to the more recent
      100-kyr cycles of ice ages. Here we analyse alkenones from marine sediments in
      the eastern equatorial Pacific Ocean to reconstruct sea surface temperatures and
      marine productivity over the past 1.8 Myr. We find that both records are
      dominated by the 41-kyr obliquity cycles between 1.8 and 1.2 Myr ago, with a
      relatively small contribution from orbital precession, and that early Pleistocene
      sea surface temperatures varied in the opposite sense to local annual insolation
      in the eastern equatorial Pacific Ocean. We conclude that during the early
      Pleistocene epoch, climate variability at our study site must have been
      determined by high-latitude processes that were driven by orbital obliquity
      forcing.

PMID- 14973482
TI  - Aftershocks driven by a high-pressure CO2 source at depth.
AB  - In northern Italy in 1997, two earthquakes of magnitudes 5.7 and 6 (separated by
      nine hours) marked the beginning of a sequence that lasted more than 30 days,
      with thousands of aftershocks including four additional events with magnitudes
      between 5 and 6. This normal-faulting sequence is not well explained with models
      of elastic stress transfer, particularly the persistence of hanging-wall
      seismicity that included two events with magnitudes greater than 5. Here we show
      that this sequence may have been driven by a fluid pressure pulse generated from
      the coseismic release of a known deep source of trapped high-pressure carbon
      dioxide (CO2). We find a strong correlation between the high-pressure front and
      the aftershock hypocentres over a two-week period, using precise hypocentre
      locations and a simple model of nonlinear diffusion. The triggering amplitude (10
      20 MPa) of the pressure pulse overwhelms the typical (0.1-0.2 MPa) range from
      stress changes in the usual stress triggering models. We propose that aftershocks
      of large earthquakes in such geologic environments may be driven by the coseismic
      release of trapped, high-pressure fluids propagating through damaged zones
      created by the mainshock. This may provide a link between earthquakes,
      aftershocks, crust/mantle degassing and earthquake-triggered large-scale fluid
      flow.

PMID- 14973483
TI  - Changes in fisheries discard rates and seabird communities.
AB  - It is clear that discards from commercial fisheries are a key food resource for
      many seabird species around the world. But predicting the response of seabird
      communities to changes in discard rates is problematic and requires historical
      data to elucidate the confounding effects of other, more 'natural' ecological
      processes. In the North Sea, declining stocks, changes in technical measures,
      changes in population structure and the establishment of a recovery programme for
      cod (Gadus morhua) will alter the amount of fish discarded. This region also
      supports internationally important populations of seabirds, some of which feed
      extensively, but facultatively, on discards, in particular on undersized haddock
      (Melanogrammus aeglefinus) and whiting (Merlangius merlangus). Here we use long
      term data sets from the northern North Sea to show that there is a direct link
      between discard availability and discard use by a generalist predator and
      scavenger--the great skua (Stercorarius skua). Reduced rates of discarding,
      particularly when coupled with reduced availability of small shoaling pelagic
      fish such as sandeel (Ammodytes marinus), result in an increase in predation by
      great skuas on other birds. This switching of prey by a facultative scavenger
      presents a potentially serious threat to some seabird communities.

PMID- 14973484
TI  - Soil biota and exotic plant invasion.
AB  - Invasive plants are an economic problem and a threat to the conservation of
      natural systems. Escape from natural enemies might contribute to successful
      invasion, with most work emphasizing the role of insect herbivores; however,
      microbial pathogens are attracting increased attention. Soil biota in some
      invaded ecosystems may promote 'exotic' invasion, and plant-soil feedback
      processes are also important. Thus, relatively rare species native to North
      America consistently demonstrate negative feedbacks with soil microbes that
      promote biological diversity, whereas abundant exotic and native species
      demonstrate positive feedbacks that reduce biological diversity. Here we report
      that soil microbes from the home range of the invasive exotic plant Centaurea
      maculosa L. have stronger inhibitory effects on its growth than soil microbes
      from where the weed has invaded in North America. Centaurea and soil microbes
      participate in different plant-soil feedback processes at home compared with
      outside Centaurea's home range. In native European soils, Centaurea cultivates
      soil biota with increasingly negative effects on the weed's growth, possibly
      leading to its control. But in soils from North America, Centaurea cultivates
      soil biota with increasingly positive effects on itself, which may contribute to
      the success of this exotic species in North America.

PMID- 14973485
TI  - Organization of genetic variation in individuals of arbuscular mycorrhizal fungi.
AB  - Arbuscular mycorrhizal (AM) fungi (Glomeromycota) are thought to be the oldest
      group of asexual multicellular organisms. They colonize the roots of most land
      plants, where they facilitate mineral uptake from the soil in exchange for plant
      assimilated carbon. Cells of AM fungi contain hundreds of nuclei. Unusual
      polymorphism of ribosomal DNA observed in individual spores of AM fungi inspired
      a hypothesis that heterokaryosis--that is, the coexistence of many dissimilar
      nuclei in cells--occurs throughout the AM fungal life history. Here we report a
      genetic approach to test the hypothesis of heterokaryosis in AM fungi. Our study
      of the transmission of polymorphic genetic markers in natural isolates of Glomus
      etunicatum, coupled with direct amplification of rDNA from microdissected nuclei
      by polymerase chain reaction, supports the alternative hypothesis of
      homokaryosis, in which nuclei populating AM fungal individuals are genetically
      uniform. Intrasporal rDNA polymorphism contained in each nucleus signals a
      relaxation of concerted evolution, a recombination-driven process that is
      responsible for homogenizing rDNA repeats. Polyploid organization of
      glomeromycotan genomes could accommodate intranuclear rDNA polymorphism and
      buffer these apparently asexual organisms against the effects of accumulating
      mutations.

PMID- 14973486
TI  - Multistability in the lactose utilization network of Escherichia coli.
AB  - Multistability, the capacity to achieve multiple internal states in response to a
      single set of external inputs, is the defining characteristic of a switch.
      Biological switches are essential for the determination of cell fate in
      multicellular organisms, the regulation of cell-cycle oscillations during mitosis
      and the maintenance of epigenetic traits in microbes. The multistability of
      several natural and synthetic systems has been attributed to positive feedback
      loops in their regulatory networks. However, feedback alone does not guarantee
      multistability. The phase diagram of a multistable system, a concise description
      of internal states as key parameters are varied, reveals the conditions required
      to produce a functional switch. Here we present the phase diagram of the bistable
      lactose utilization network of Escherichia coli. We use this phase diagram,
      coupled with a mathematical model of the network, to quantitatively investigate
      processes such as sugar uptake and transcriptional regulation in vivo. We then
      show how the hysteretic response of the wild-type system can be converted to an
      ultrasensitive graded response. The phase diagram thus serves as a sensitive
      probe of molecular interactions and as a powerful tool for rational network
      design.

PMID- 14973487
TI  - Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks
      chain migration.
AB  - The subventricular zone (SVZ) is a principal source of adult neural stem cells in
      the rodent brain, generating thousands of olfactory bulb neurons every day. If
      the adult human brain contains a comparable germinal region, this could have
      considerable implications for future neuroregenerative therapy. Stem cells have
      been isolated from the human brain, but the identity, organization and function
      of adult neural stem cells in the human SVZ are unknown. Here we describe a
      ribbon of SVZ astrocytes lining the lateral ventricles of the adult human brain
      that proliferate in vivo and behave as multipotent progenitor cells in vitro.
      This astrocytic ribbon has not been observed in other vertebrates studied.
      Unexpectedly, we find no evidence of chains of migrating neuroblasts in the SVZ
      or in the pathway to the olfactory bulb. Our work identifies SVZ astrocytes as
      neural stem cells in a niche of unique organization in the adult human brain.

PMID- 14973488
TI  - Direct interaction of geminin and Six3 in eye development.
AB  - Organogenesis in vertebrates requires the tight control of cell proliferation and
      differentiation. The homeobox-containing transcription factor Six3 plays a
      pivotal role in the proliferation of retinal precursor cells. In a yeast two
      hybrid screen, we identified the DNA replication-inhibitor geminin as a partner
      of Six3. Geminin inhibits cell-cycle progression by sequestering Cdt1 (refs 4,
      5), the key component for the assembly of the pre-replication complex. Here, we
      show that Six3 efficiently competes with Cdt1 directly to bind to geminin, which
      reveals how Six3 can promote cell proliferation without transcription. In common
      with Six3 inactivation, overexpression of the geminin gene (Gem; also known as
      Gmn) in medaka (Oryzias latipes) induces specific forebrain and eye defects that
      are rescued by Six3. Conversely, loss of Gem (in common with gain of Six3 (ref.
      1)) promotes retinal precursor-cell proliferation and results in expanded optic
      vesicles, markedly potentiating Six3 gain-of-function phenotypes. Our data
      indicate that the transcription factor Six3 and the replication-initiation
      inhibitor geminin act antagonistically to control the balance between
      proliferation and differentiation during early vertebrate eye development.

PMID- 14973489
TI  - The cell-cycle regulator geminin inhibits Hox function through direct and
      polycomb-mediated interactions.
AB  - Embryonic development is tightly controlled. The clustered genes of the Hox
      family of homeobox proteins play an important part in regulating this development
      and also proliferation. They specify embryonic structures along the body axis,
      and are associated with normal and malignant cell growth. The cell-cycle
      regulator geminin controls replication by binding to the licensing factor Cdt1,
      and is involved in neural differentiation. Here, we show that murine geminin
      associates transiently with members of the Hox-repressing polycomb complex, with
      the chromatin of Hox regulatory DNA elements and with Hox proteins. Gain- and
      loss-of-function experiments in the chick neural tube demonstrate that geminin
      modulates the anterior boundary of Hoxb9 transcription, which suggests a polycomb
      like activity for geminin. The interaction between geminin and Hox proteins
      prevents Hox proteins from binding to DNA, inhibits Hox-dependent transcriptional
      activation of reporter and endogenous downstream target genes, and displaces Cdt1
      from its complex with geminin. By establishing competitive regulation, geminin
      functions as a coordinator of developmental and proliferative control.

PMID- 14973490
TI  - An eIF4AIII-containing complex required for mRNA localization and nonsense
      mediated mRNA decay.
AB  - The specification of both the germ line and abdomen in Drosophila depends on the
      localization of oskar messenger RNA to the posterior of the oocyte. This
      localization requires several trans-acting factors, including Barentsz and the
      Mago-Y14 heterodimer, which assemble with oskar mRNA into ribonucleoprotein
      particles (RNPs) and localize with it at the posterior pole. Although Barentsz
      localization in the germ line depends on Mago-Y14, no direct interaction between
      these proteins has been detected. Here, we demonstrate that the translation
      initiation factor eIF4AIII interacts with Barentsz and is a component of the
      oskar messenger RNP localization complex. Moreover, eIF4AIII interacts with Mago
      Y14 and thus provides a molecular link between Barentsz and the heterodimer. The
      mammalian Mago (also known as Magoh)-Y14 heterodimer is a component of the exon
      junction complex. The exon junction complex is deposited on spliced mRNAs and
      functions in nonsense-mediated mRNA decay (NMD), a surveillance mechanism that
      degrades mRNAs with premature translation-termination codons. We show that both
      Barentsz and eIF4AIII are essential for NMD in human cells. Thus, we have
      identified eIF4AIII and Barentsz as components of a conserved protein complex
      that is essential for mRNA localization in flies and NMD in mammals.

PMID- 14973491
TI  - Pitching ideas.

PMID- 14973492
TI  - Short-term limbo.

PMID- 14973494
TI  - Scientists and societies. Protecting the public investment.

PMID- 14973496
TI  - Role of high-dose chemotherapy with hematopoietic stem-cell rescue for multiple
      myeloma.

PMID- 14973497
TI  - Cyclin-dependent kinase inhibitor Roscovitine induces apoptosis in chronic
      lymphocytic leukemia cells.
AB  - A new class of cell cycle inhibitors is currently entering clinical trials. These
      drugs exert their activity by inhibition of cyclin-dependent kinases (cdk) and
      induce cell cycle arrest and apoptosis in cancer cells. Roscovitine, a cdk2
      inhibitor that is in preclinical evaluation, induced apoptosis in B-CLL cells at
      doses that were not cytotoxic for normal human B cells. At 20 microM, Roscovitine
      induced apoptosis in 21 of 28 B-CLL samples and was equally effective in zap-70
      positive or -negative samples. Caspase-3 was cleaved in B-CLL cells exposed to
      Roscovitine and the pancaspase inhibitor z.VAD.fmk-blocked Roscovitine-induced
      apoptosis. Expression of the proapoptotic protein Bak was increased and Bax
      cleavage and conformational change was observed in Roscovitine-treated B-CLL
      cells. Antiapoptotic proteins Mcl-1 and XIAP were downregulated, but the
      expression of Bcl-2 remained unchanged. In contrast to previous reports in cancer
      cell lines, Roscovitine treatment was not accompanied by nuclear accumulation of
      p53. Cyc202 (R-Roscovitine) is in early clinical trials in cancer patients. Given
      its powerful effects on zap-70-positive and -negative B-CLL cells, but not on
      normal lymphocytes, Roscovitine might be an attractive drug to be tested in this
      incurable disease.

PMID- 14973498
TI  - Expression of the p14ARF tumor suppressor predicts survival in acute myeloid
      leukemia.
AB  - Cell cycle aberrations are associated with therapy outcome in many types of
      cancer. We analyzed mRNA expression levels of 18 cell cycle-related genes in bone
      marrow samples from 78 acute myeloid leukemia (AML) patients and six controls
      using high-throughput quantitative RT-PCR. Samples of AML patients contained
      significantly increased mRNA expression levels of the mdm2 and c-myc oncogenes.
      Also, the average expression levels of p14ARF and p16INK4A were higher in patient
      samples compared to controls. Leukemic blasts and control bone marrow samples did
      not differ significantly in the expression levels of proliferation-associated
      genes such as cyclin A2 and pcna. When single genes were analyzed for prognostic
      significance in Kaplan-Meier and Cox regression analyses, a low p14ARF level
      emerged as a strong and independent predictor for poor survival (P=0.04 and
      0.029). Subsequently, p14ARF mRNA levels were analyzed in a second, independent
      patient population (n=57). Again, low p14ARF levels were associated with a worse
      outcome. Finally, immunohistochemistry analysis of AML tissue arrays confirmed
      the widespread expression of c-myc and p14ARF in AML on the protein level. Taken
      together, the expression of the p53 regulators mdm2 and p14ARF are altered in
      AML, and low p14ARF levels indicate a poor prognosis.

PMID- 14973499
TI  - Direct cloning of leukemia-reactive T cells from patients treated with donor
      lymphocyte infusion shows a relative dominance of hematopoiesis-restricted minor
      histocompatibility antigen HA-1 and HA-2 specific T cells.
AB  - Donor T cells recognizing hematopoiesis-restricted minor histocompatibility
      antigens (mHags) HA-1 and HA-2 on malignant cells play a role in the antileukemia
      effect of donor lymphocyte infusion (DLI) in patients with relapsed leukemia
      after allogeneic stem cell transplantation. We quantified the contribution of HA
      1 and HA-2 specific T cells to the total number of leukemia-reactive T cells in
      three HA-2 and/or HA-1 positive patients responding to DLI from their mHag
      negative donors. Clinical responses occurring 5-7 weeks after DLI were
      accompanied by an increase in percentages HLA-DR expressing T cells within the
      CD8+ T cell population. To clonally analyze the leukemia-reactive immune
      response, T cells responding to the malignancy by secreting IFNgamma were
      isolated from peripheral blood, directly cloned, and expanded. Tetramer analysis
      and specific lysis of peptide-pulsed target cells showed that 3-35% of cytotoxic
      T lymphocyte (CTL) clones isolated were specific for HA-1 or HA-2. TCR VB
      analysis showed oligoclonal origin of the HA-1 and HA-2 specific CTL clones. The
      HA-1 and HA-2 specific CTL clones inhibited leukemic progenitor cell growth in
      vitro. The relatively high frequency of HA-1 and HA-2 specific T cells within the
      total number of tumor-reactive T cells illustrates relative immunodominance of
      mHags HA-1 and HA-2.

PMID- 14973500
TI  - Integrins regulate survival of pre-B-ALL cells through differential IAP and
      caspase-7 ubiquitination and degradation.

PMID- 14973501
TI  - Abnormal mRNA expression of ASPP members in leukemia cell lines.

PMID- 14973502
TI  - Detection of ABL kinase domain mutations with denaturing high-performance liquid
      chromatography.
AB  - Mutations of the ABL kinase domain (KD) are common in patients with chronic
      myelogenous leukemia (CML) who develop resistance to imatinib. We developed an RT
      PCR-based denaturing high-performance liquid chromatography (D-HPLC) assay to
      detect mutations of the ABL KD. Validation experiments using mixtures of wild
      type and mutant amplicons showed that the D-HPLC assay could detect mutant
      transcripts when they represented at least 15% of the total, and was thus twice
      as sensitive as automated sequencing. When D-HPLC was applied to 30 cDNAs from
      patients with imatinib resistance that had previously been characterized for KD
      mutations by direct sequencing of BCR-ABL RT-PCR products, there was concordance
      in 97% of samples. Resequencing confirmed the original mutations in all cases. In
      addition, sequencing of individual clones detected a mutation in one sample that
      had been mutation-positive by D-HPLC but wild type by conventional sequencing. In
      serial samples from the same individuals, D-HPLC detected mutations as early as
      260 days before hematological relapse. D-HPLC is suitable for routine clinical
      monitoring of CML patients for emergence of KD mutations and may be useful for
      optimizing therapy. Early detection of emerging mutant clones may aid in guiding
      decisions regarding alternative treatment options.

PMID- 14973503
TI  - Revisiting the definition of somatic mutational status in B-cell tumors: does 98%
      homology mean that a V(H)-gene is unmutated?

PMID- 14973504
TI  - Clinical and molecular features of FIP1L1-PDFGRA (+) chronic eosinophilic
      leukemias.
AB  - Detection of the FIP1L1-PDGFRA fusion gene or the corresponding cryptic 4q12
      deletion supports the diagnosis of chronic eosinophilic leukemia (CEL) in
      patients with chronic hypereosinophilia. We retrospectively characterized 17
      patients fulfilling WHO criteria for idiopathic hypereosinophilic syndrome (IHES)
      or CEL, using nested RT-PCR and interphase fluorescence in situ hybridization
      (FISH). Eight had FIP1L1-PDGFRA (+) CEL, three had FIP1L1-PDGFRA (-) CEL and six
      had IHES. FIP1L1-PDGFRA (+) CEL responded poorly to steroids, hydroxyurea or
      interferon-alpha, and had a high probability of eosinophilic endomyocarditis
      (n=4) and disease-related death (n=4). In FIP1L1-PDGFRA (+) CEL, palpable
      splenomegaly was present in 5/8 cases, serum vitamin B(12) was always markedly
      increased, and marrow biopsies revealed a distinctively myeloproliferative
      aspect. Imatinib induced rapid complete hematological responses in 4/4 treated
      FIP1L1-PDGFRA (+) cases, including one female, and complete molecular remission
      in 2/3 evaluable cases. In the female patient, 1 log reduction of FIP1L1-PDGFRA
      copy number was reached as by real-time quantitative PCR (RQ-PCR). Thus,
      correlating IHES/CEL genotype with phenotype, FIP1L1-PDGFRA (+) CEL emerges as a
      homogeneous clinicobiological entity, where imatinib can induce molecular
      remission. While RT-PCR and interphase FISH are equally valid diagnostic tools,
      the role of marrow biopsy in diagnosis and of RQ-PCR in disease and therapy
      monitoring needs further evaluation.

PMID- 14973505
TI  - Defective class II transactivator expression in a B lymphoma cell line.
AB  - Loss of MHC class II expression in B-cell lymphoma has been associated with a
      higher tumorigenicity resulting from lower titers of tumor-infiltrating
      lymphocytes. This report aims towards the identification of the molecular
      mechanism leading to defective MHC class II expression in a B-cell lymphoma cell
      line, Rec-1. We evidenced a coordinated alteration of HLA-D gene transcription,
      reminiscent of B lymphoblastoid cell lines from patients with MHC class II
      deficiency. Genetic complementation performed between these cell lines and the
      lymphoma cells indicated that Rec-1 is altered in the MHC2TA gene. MHC2TA encodes
      the class II transactivator (CIITA), the master regulator of HLA-D gene
      expression. However, the coding sequence of the Rec-1 CIITA transcript did not
      reveal any mutation that could hamper the activity of the encoded protein. In
      agreement with the genetic complementation analysis, we evidenced a highly
      residual CIITA protein expression in the Rec-1 cell line resulting from a
      transcriptional defect affecting MHC2TA expression. Anti-HLA-DR monoclonal
      antibody treatment has proved efficient in the destruction of B lymphoma cells.
      Our data indicate that the appearance of variants losing CIITA, and thereby HLA
      DR, expression will require a thorough monitoring during such immunotherapy
      protocols.

PMID- 14973506
TI  - Erythroleukaemia and RAEB-t: a same disease?

PMID- 14973507
TI  - The higher expression of alpha and beta isoforms of the human glucocorticoid
      receptor in leukemic B-progenitors compared to normal CD10+ BM cells does not
      correlate with methylprednisolone-induced apoptosis.

PMID- 14973508
TI  - The oral combination of thalidomide, cyclophosphamide and dexamethasone
      (ThaCyDex) is effective in relapsed/refractory multiple myeloma.
AB  - We evaluate the efficacy of the oral combination of thalidomide, cyclophosphamide
      and dexamethasone (ThaCyDex) in 71 refractory/relapsed multiple myeloma patients,
      including a prognostic analysis to predict both response and survival. Patients
      received thalidomide at escalating doses (200-800 mg/day), daily cyclophosphamide
      (50 mg/day) and pulsed dexamethasone (40 mg/day, 4 days every 3 weeks). On an
      intention-to-treat basis and using the EBMT response criteria, 2% patients
      reached complete response (CR), 55% partial response (PR) and 26% minor response
      (MR) yielding a total response (CR+PR+MR) rate of 83% after 3 months of therapy.
      After 6 months of therapy, responses were maintained including a 10% CR. The 2
      year progression free and overall survival were 57 and 66%, respectively. A
      favorable response was associated with beta2 microglobulin < or =4 mg/dl,
      platelets >80 x 10(9)/l and nonrefractory disease. Regarding survival, low beta2
      microglobulin (< or =4 mg/dl), age (< or =65 years) and absence of extramedullary
      myelomatous lesion were associated with a longer survival. Major adverse effects
      included constipation (24%), somnolence (18%), fatigue (17%) and infection (13%).
      Only 7% of patients developed a thrombo-embolic event. ThaCyDex is an oral
      regimen that induces a high response rate and long remissions, particularly in
      relapsing patients with beta2 microglobulin < or =4 mg/dl and < or =65 years.

PMID- 14973509
TI  - Sudden infant death syndrome among extremely preterm infants: United States 1997
      1999.
AB  - BACKGROUND: Preterm infants have been reported to be at higher risk than term
      infants for sudden infant death syndrome (SIDS). Reasons for this higher risk are
      not clear. OBJECTIVE: The objective of this study was to analyze medical and
      demographic characteristics among infants 24 to 32 weeks gestation to identify
      characteristics more prevalent among infants dying of SIDS in the postneonatal
      period than among infants of similar gestation who survived or who died of other
      causes in the postneonatal period. DESIGN/METHODS: United States linked birth and
      death certificate period data for 1997 to 1999 were used for this analysis. The
      population used was limited to infants 24 to 32 weeks gestation weighing 500 to
      2500 g. SIDS deaths were limited to the postneonatal period and compared to
      survivors and infants dying in the postneonatal period of other causes. RESULTS:
      There were 469 postneonatal SIDS deaths with complete data (rate=2.2/1000 live
      births surviving > or =28 days); 3950 other postneonatal deaths (rate=18.7/1000)
      and 206,640 survivors. Compared with survivors, infants dying of SIDS were more
      likely to be born to mothers with <12 years of education (odds ratio=2.5, 95%
      confidence interval (95% CI=1.8, 3.3); be born to mothers < or =17 years of age
      (OR=2.0, 95% CI=1.4, 2.8); and be born to mothers with >3 previous pregnancies
      (OR=2.6, 95% CI=1.9, 3.5). Compared with infants dying in the postneonatal period
      of other causes, these same demographic factors continued to be significant risk
      factors for SIDS. There were no medical risk factors such as breech presentation,
      abruptio placenta, Apgar score <4 at 5 minutes, or mechanical ventilation for >30
      minutes after birth, for which infants dying of SIDS were at greater risk than
      survivors or infants dying of other causes. CONCLUSIONS: Risk factors for SIDS
      among infants 24 to 32 weeks gestation appear to be more associated with
      sociodemographic characteristics than medical characteristics. This suggests that
      for the immediate future, the risk for SIDS among very preterm infants will be
      best addressed through further modification of the environment and parent
      behavior.

PMID- 14973510
TI  - Evaluation of neutropenia and neutrophilia in hospitalized preterm infants.
AB  - OBJECTIVES: To characterize the time course of changes in neutrophil counts, and
      to draw comparisons across four gestational age groups with respect to incidence
      of neutropenia and neutrophilia over the first months of life in a single center.
      STUDY DESIGN: Weekly complete blood counts (CBC) were collected on all NICU
      patients. Changes in neutrophil counts over time were examined, the incidence of
      neutropenia (< or =1100/mm3) and neutrophilia (> or =15,000/mm3 before, and > or
      =6000/mm3 after 60 hours of life) were determined, and clinical correlations
      sought. RESULTS: A total of 2038 CBCs from 347 infants were evaluated. Changes in
      neonatal neutrophil counts were associated with gestational age, postnatal age,
      pregnancy-induced hypertension (PIH), and infection, either presumed or
      documented. Overall, neutropenia occurred 91 times in 50 infants (14% of
      infants), and the prevalence decreased with maturity and increased with exposure
      to PIH. In the first week of life, 69% of the neutropenia occurred in infants
      exposed to PIH. Neutrophilia occurred 579 times in 146 infants (42% of infants),
      and the prevalence decreased with maturity. Neutrophil deviations from the normal
      range were often asymptomatic and not associated with recognized clinical
      conditions. CONCLUSIONS: The incidence and prevalence of neutrophil abnormalities
      increased with immaturity, and were more common than previously appreciated in
      hospitalized preterm infants.

PMID- 14973511
TI  - Herpes simplex virus infection after vacuum-assisted vaginally delivered infants
      of asymptomatic mothers.
AB  - OBJECTIVE: To determine whether vacuum extraction technique is associated with an
      increased risk of herpes simplex virus (HSV) infection in infants born to
      asymptomatic mothers. PATIENTS AND METHODS: We reviewed the charts of all infants
      born at the Edith Wolfson Medical Center and admitted to the hospital's neonatal
      intensive care unit from January 1999 to June 2002 diagnosed with HSV infection.
      RESULTS: During the study period, 6953 infants were delivered at our institution
      and 11 infants had HSV infection. The prevalence of neonatal HSV infection was
      1.6 per 1000 live births. In 699 infants, vacuum extraction was used for
      delivery. Five out of the 11 infants delivered vaginally by vacuum extraction
      developed HSV infection at the site of the vacuum extractor application. They
      were born to mothers who were asymptomatic at delivery and had no history of HSV
      genital infection. HSV type 2 was isolated from the vesicular fluid in all
      infected infants delivered by vacuum extraction, and none had central nervous
      system involvement. The prevalence of neonatal HSV infection in vacuum-assisted
      births was seven per 1000 live births as compared to 0.95 in 1000 in infants
      delivered vaginally or by cesarean section (p<0.0001). The relative risk of HSV
      infection in infants born in vacuum-assisted births was 7.45 (95% confidence
      interval (CI) 1.99 to 27.42, p=0.001). All patients were treated with intravenous
      acyclovir and no recurrences of HSV infection have been noticed at follow-up.
      CONCLUSIONS: Laceration of the fetal scalp by vacuum extraction technique may
      enhance the acquisition and the early appearance of cutaneous infection in
      infants exposed to HSV shedding in the genital tract of asymptomatic mothers, as
      the virus gains access through the lacerated scalp.

PMID- 14973512
TI  - Guidelines for management of hypertension: report of the fourth working party of
      the British Hypertension Society, 2004-BHS IV.

PMID- 14973513
TI  - Blood pressure in acute intracerebral haemorrhage.
AB  - Stroke is one of the leading causes of death worldwide, and spontaneous bleeding
      into the brain parenchyma, intracerebral haemorrhage (ICH), is a stroke subtype
      associated with high morbidity and mortality. Overall, it comprises about 15% of
      all stroke in Caucasians, this figure being much higher in Asians and black
      people. Blood pressure (BP) appears to play an important role in this disease. We
      have reviewed available literature on the relationship of BP to the occurrence of
      primary and secondary ICH, the association of BP levels measured early after
      stroke with prognosis and complications, and evidence about the effects of early
      BP lowering treatments on post-stroke outcomes. BP appears to be an important
      risk factor for primary and secondary ICH. In addition, high BP early after ICH
      may be detrimental to outcome, possibly contributing to complications such as
      rebleeding and haematoma enlargement. Few data are available about the effects of
      early lowering of BP on outcome after ICH with no reliable trial yet conducted.
      Proper randomised trials are required to establish the effect of early lowering
      of BP on outcome after ICH.

PMID- 14973514
TI  - Office blood pressure underestimates ambulatory blood pressure in peripheral
      arterial disease in comparison to healthy controls.
AB  - Patients with peripheral arterial disease (PAD) constitute a subgroup of high
      risk hypertensives, but controlled studies on 24-h blood pressure (BP) and
      diurnal variation of BP are lacking. This study was performed in order to test
      the hypothesis that office BP (OBP) may underestimate 24-h BP in PAD patients in
      comparison to a matched control group. In all, 98 male patients (mean age 68
      years) with a history of intermittent claudication and an ankle/brachial index
      less than 0.9, and 94 controls matched for age but without PAD or ischaemic heart
      disease performed 24-h recordings of ambulatory BP. A total of 59 patients had a
      history of hypertension and 69 were on treatment with BP-lowering drugs as
      compared to 17 and 23 of the control subjects, respectively. Office as well as 24
      h systolic BP (SBP) were higher in patients as compared to controls (151 +/- 22
      vs 140 +/- 20 mmHg, P < 0.001 and 142 +/- 14 vs 133 +/- 15 mmHg, P < 0.001,
      respectively), but did not differ with regard to diastolic BP. In an analysis of
      covariance with the continuous factors age, office SBP and the categorical factor
      antihypertensive treatment, 24-h SBP was higher in PAD patients compared to
      controls (P < 0.05). The difference between office and night SBP was lower in PAD
      patients with antihypertensive treatment compared to controls (P = 0.01). In
      conclusion, Male patients with PAD had higher systolic but not diastolic BP than
      age-matched control subjects. In PAD patients, 24-h SBP was higher than expected
      from OBP compared to controls. Night SBP was higher only in patients with
      antihypertensive treatment. In PAD patients, especially when on antihypertensive
      treatment, the severity of hypertension may be underestimated when based on OBP
      only.

PMID- 14973515
TI  - Early carotid atherosclerosis and cardiac diastolic abnormalities in hypertensive
      subjects.
AB  - Despite the fact that it is known that hypertension may be associated to early
      atherosclerosis manifestations, few data are to date available on the
      relationship between early carotid abnormalities and left ventricular diastolic
      dysfunction. To address this issue, 142 hypertensive patients (64 females and 78
      males) younger than 55 years, at the first diagnosis of mild-to-moderate
      essential hypertension (WHO/ISH criteria), were selected from a database
      consisting of 3541 subjects referred to ultrasound cardiovascular laboratory in
      the last 5 years. Carotid intima-media thickness (IMT) was detected by high
      resolution vascular ultrasound and left ventricular structure and function by the
      use of Doppler echocardiography. According to carotid IMT values, all patients
      were subgrouped into two groups consisting of 89 (62.6%) pts with IMT > or = 1 mm
      (A) and 53 (37.4%) pts with IMT < 1 mm (B). Our results show that isovolumic
      relaxation time (IVRT), deceleration time of E velocity (EDT) and left
      ventricular relative wall thickness (LV-RWT) were significantly (P < 0.05) higher
      in group A (IVRT 112 +/- 8.9 ms; EDT 288 +/- 21.8 ms; LV-RWT 0.40 +/- 0.08) than
      in group B (IVRT 92.3 +/- 4.6 ms; EDT 203.3 +/- 27.01 ms; LV- RWT 0.37 +/- 0.06).
      Moreover, the prevalence of left ventricular hypertrophy (LVH) was significantly
      (P < 0.01) higher in group A (30/89; 33.7%) than in group B (8/53; 15%). A
      positive correlation (P < 0.001) between IMT, EDT and IVRT was found only in
      hypertensives without LVH. These results are consistent with the indication that
      IMT evaluation has to be recommended both in hypertensive patients with LVH and
      in those without LVH, but with left ventricular diastolic dysfunction. This
      approach might improve the prognostic stratification of hypertensive subjects and
      it might be suitable to recognize the subset of patients at a higher risk of
      cardiovascular disease or events early.

PMID- 14973516
TI  - Risk factors for uncontrolled hypertension in Italy.
AB  - To identify factors related to poor control of blood pressure in primary care, we
      designed a retrospective case-control analysis of clinical and demographic data
      recorded in the General Practitioners (GP) database. Study data were provided on
      a voluntary basis by 21 GPs from a practice-based network in primary care. The
      study included 2519 hypertensive patients enrolled between January 1 and December
      31, 2000. The interventions were antihypertensive medication, and the main
      outcome measures were control of systolic and diastolic blood pressure (BP). The
      independent variables considered were: age of patient and GP; patient gender,
      body mass index, history of smoking, diabetes mellitus, or cholesterol tests;
      family history of hypertension; previous visits for cardiologic, nephrologic, or
      vascular surgery evaluation; prior hospitalizations for myocardial infarction or
      heart failure, and number of admissions for surgery; length of patient follow-up,
      type of antihypertensive medication, mean daily dosage, adherence to the drug
      regimen, and number of other medications currently being taken by the patient.
      Blood pressure was uncontrolled (>140/90 mmHg) in 1525 (60%) of the 2519
      hypertensive patients enrolled. The presence of diabetes mellitus, increasing
      patient age, and increasing GP age significantly increased the risk of
      uncontrolled BP. Factors significantly associated with a reduced risk of
      uncontrolled BP were the number of other medications currently being taken by the
      patient and a prior history of MI. We conclude that the failure of
      antihypertensive medication to adequately control BP is determined by both the
      patient's characteristics and factors related to the patient-doctor relationship.
      Successful treatment of hypertension requires patient adherence to the regimen
      that has been agreed on by the patient and the physician.

PMID- 14973517
TI  - Comparison of the antihypertensive effects of the fixed dose combination
      enalapril 10 mg/nitrendipine 20 mg vs losartan 50 mg/hydrochlorothiazide 12.5 mg,
      assessed by 24-h ambulatory blood pressure monitoring, in essential hypertensive
      patients.
AB  - Fixed combinations of calcium channel blockers and angiotensin converting enzyme
      inhibitors represent an alternative to diuretic-based combination therapy. The
      aim of the present study was to compare the antihypertensive efficacy of the
      combination enalapril 10 mg/nitrendipine 20 mg (E/N) vs losartan 50
      mg/hydrochlorothiazide 12.5 mg (L/H), assessed by 24-h ambulatory blood pressure
      monitoring. This multicentre, double-blind, parallel study included 97
      hypertensive patients (office diastolic blood pressure (DBP) 90-109 mmHg and
      daytime DBP > 85 mmHg). After a 2- to 3-week period of single-blind placebo, they
      were randomized to receive double-blind treatment with E/N (n = 48) or L/H (n =
      49) for a 4-week period. The primary outcome measure was the difference in 24-h
      DBP reduction between treatments from randomization to the end of the double
      blind period. Secondary efficacy variables included differences in 24-h systolic
      (S) BP reduction, daytime, night-time and office SBP and DBP reduction,
      proportion of responders and controlled patients, trough-to-peak ratio and
      smoothness indexes. Safety was assessed by the proportion of patients with
      adverse events and the detection of laboratory abnormalities. No significant
      differences were observed in the primary outcome measure. The group receiving E/N
      tended to show greater reductions in most measures (24 h, daytime and office SBP
      and DBP) and higher BP control rates, but only the difference in the rate of
      office SBP control (< 140 mmHg) reached statistical significance (42.2 vs 22.4%;
      P = 0.048). The trough-to-peak ratios and smoothness indexes were similar in both
      groups. The incidence of adverse events related to the treatment was 27.1% (95%
      CI 14.5-39.6%) in E/N-treated patients and 14.3% (95% CI 4.5-45.8%) in the L/H
      group, but differences were not significant. The kind of event more frequently
      observed were flushing and headache in E/N, and dizziness and asthenia in L/H;
      all observed adverse events were mild. We conclude that E/N and L/H have a
      similar antihypertensive efficacy, assessed by office or ambulatory blood
      pressure monitoring. E/N achieved a significantly higher office SBP control rate,
      but this was accompanied by an apparently higher proportion of mild adverse
      events.

PMID- 14973518
TI  - Work-site hypertension prevalence and control in three Central European
      Countries.
AB  - Compared to Austria, cerebrovascular stroke (CVS) mortality is three times higher
      in Hungary, and twice as high in Slovakia. We hypothesized that this is due to
      better treatment and control of hypertension in Austria. To test this hypothesis,
      we carried out a cross-sectional survey of 'blue collar' employees on work sites
      in each of these countries. Blood pressure screening was carried out at three
      work sites in Austria, one in Hungary and one in Slovakia. A standardized
      protocol was followed in each of these countries. The Bp-TRU(TM) measuring
      instrument was used to provide accurate reproducible readings and eliminate
      interobserver error. After the exclusion of missing data and women, the study
      population included 323 males screened in Austria, 600 in Hungary, and 751 in
      Slovakia. The mean ages of the respondents ranged from 35 to 42 years. The
      prevalence of hypertension was 29% in Austria, 28% in Hungary and 40% in
      Slovakia. Of those identified as hypertensive, 73% in Austria, 45% in Hungary and
      67% in Slovakia were newly diagnosed as a result of this screening. Of those
      treated for hypertension, 10% in Austria, 15% in Hungary and 5% in Slovakia were
      controlled. The differences in CVS mortality cannot be explained by better
      control of hypertension in Austria but indicate the involvement of other
      determinants.

PMID- 14973519
TI  - Epidemiology of hypertension and its associated risk factors in the Qatari
      population.

PMID- 14973520
TI  - The renin-angiotensin-aldosterone system in atrial fibrillation: a new
      therapeutic target?

PMID- 14973521
TI  - Effect of aging on quality of nocturnal erections: evaluation with NPTR testing.
AB  - Nocturnal penile tumescence and rigidity testing (NPTR) has traditionally been
      performed to distinguish psychogenic from organic impotence. However,
      considerable lack of uniformly accepted normative data for NPTR readings makes
      the reproducibility of the method questionable. In this study, we try to evaluate
      the impact of aging as independent criteria for quality of erectile episodes. A
      total of 455 patients (ages 20-71 y) whose initial complaints were erectile
      dysfunction underwent two nights NPTR measurement with Rigiscan device. After
      analyzing the data, 353 men out of 455 were regarded as having normal NPTR
      recordings. The number of normal erectile episodes (erectile episode of penile
      tip rigidity greater than 60% more than 10 min duration), RAU Tip, RAU Base, TAU
      Tip, TAU Base, Average event rigidity of Tip (%), Average event rigidity of Base
      (%) and Duration of erectile episodes > or =60% minute were re-evaluated with
      regard to five age groups (group I: <30 y; group II: 30-39 y; group III: 40-49 y;
      group IV: 50-59 y; group V: > or =60 y). The mean values of erectile episodes in
      the age groups were as follows: group I, 2.46; group II, 2.28; group III, 2.40;
      group IV, 1.58; group V, 1.27. When we analyzed the groups between themselves, we
      observed statistically significant difference after the age of 50 y. The mean
      erectile episodes in patients younger than 50 y were 2.37 (s.d.: 1.50), whereas
      1.49 (s.d.: 1.15) in patients older than 50 y (P<0.001). We also observed
      statistically significant difference at all of the above-mentioned NPTR
      parameters with regard to age. The results of our study showed that aging
      negatively influence quality of nocturnal erections especially after 50 y and we
      suggest that age needs to be taken into account in the diagnostic interpretation
      of NPTR testing.

PMID- 14973522
TI  - Impact of spinal cord injury on sexual health and quality of life.
AB  - To provide a comprehensive insight into sexuality after spinal cord injury, 120
      patients received a questionnaire to assess their sexual activities, abilities,
      desires, satisfaction and sexual adjustment after injury. In the 63 responding
      patients, spinal cord injury had a major impact on sexual function. Relationship
      to partner, social life, bladder management and physical well-being had a
      significant impact on quality of life. Relationship to partner, ability to move
      and mental well-being, as well as aspects of sexual desire and body image had a
      significant correlation to satisfaction with sexual life. In the studied
      population, there was no significant correlation between preserved sexual
      abilities after spinal cord injury and the satisfaction with sexual life.

PMID- 14973523
TI  - Extracorporeal shockwave therapy for Peyronie's disease does not correct penile
      deformity.
AB  - To evaluate whether extracorporeal shockwave therapy (ESWT) offers an effective
      treatment for the main complications of Peyronie's disease (PD), that is, penile
      deformity and angulation, painful erection and most importantly unsatisfied
      sexual intercourse. From September 1999 to January 2001, 52 patients with PD were
      treated with ESWT. Pain during erection was assessed with a visual analogue
      scale. Penile deviation was determined by photographs with a goniometer. Five
      treatment sessions were performed at weekly intervals. Each consisted of 3000
      shockwaves with an emission frequency of 120 shockwaves/min and a mean intensity
      of 0.17 mJ/mm(2). A Storz Minilith SL 1 with integrated inline ultrasound probe
      was used. In all, 52 patients were evaluated 6 weeks after ESWT for early follow
      up. Before ESWT intercourse was difficult or impossible for 40 men; 29 patients
      suffered mainly from penile deformity, 14 from painful erection and eight mainly
      from loss of distal rigidity. A total of 30 patients mentioned painful erection
      before treatment. In 28 patients (93%) pain reduction was achieved. A total
      relief of pain was observed in 19 patients (63%). Mean pain score dropped from
      4.2 to 1.3 in patients who suffered predominantly from painful erections.
      Intercourse satisfaction improved in 11 patients after therapy. Mean angulation
      before (40 degrees ) and after (37 degrees ) ESWT did not change significantly.
      Late follow-up after 11.1 months (4-17 months) could be completed in 36 patients.
      In total, 19 men reported that ESWT improved their PD. Of these, 16 noted no
      change. Only one of the patients noticed a worsening of his disease during or
      after treatment. Complication rate was low with only minor side effects such as
      minimal skin bruising; one urethral bleeding occurred. ESWT did reduce pain
      during erection in patients suffering mainly from painful erection due to PD.
      However, penile angulation did not improve significantly in our setup and thus
      intercourse difficulties did improve only in 28% of the patients. Therefore, we
      do not recommend ESWT as a primary treatment for PD.

PMID- 14973524
TI  - Patterns of use of sildenafil among commercially insured adults in the United
      States: 1998-2002.
AB  - Sildenafil is increasingly being marketed to younger healthcare consumers. The
      purpose of this study was to profile sildenafil use in commercially insured,
      adult beneficiaries. Annual ambulatory prescription claims data from 1998 to
      2002, for a nationwide, random sample of over 5 million life-years of
      commercially insured adults (aged > or =18 y), were examined retrospectively. The
      overall prevalence of sildenafil use increased from 0.8% (1998) to 1.4% (2002),
      an 84% increase. While the growth in use slowed in older males, use became more
      pronounced in younger males and females and decreased in older females. The
      fastest growing segment of users was found to be males aged 18-45 y. The
      proportion of users who had two or more claims for a medication that is suspected
      of inducing erectile dysfunction (ED) and/or a marker for a suspected ED-inducing
      disease decreased over the study period. Our findings suggest that use may
      increase among younger male and female patients and those without an underlying
      etiologic reason for use.

PMID- 14973525
TI  - Effect of insulin-like growth factor-1 and insulin-like growth factor binding
      protein-3 complex in cavernous nerve cryoablation.
AB  - The purpose of this work was to study the effect of insulin-like growth factor 1
      (IGF-1) and its binding protein (IGFBP-3) on the recovery of erectile function in
      a rat model for neurogenic impotence. In all, 28 male Sprague-Dawley rats were
      divided into four groups: seven underwent a sham operation; seven underwent
      bilateral cavernous nerve freezing (control group); seven underwent bilateral
      cavernous nerve freezing followed by intraperitoneal injection of IGF-1; and
      seven underwent bilateral cavernous nerve freezing followed by intraperitoneal
      injection of IGFBP-3. Erectile response was assessed by cavernous nerve
      electrostimulation at 3 months, and samples of penile tissue were evaluated
      histochemically for nitric oxide synthase (NOS)-containing fibers. In the sham
      and IGF-1 group, there were significantly higher maximal intracavernous pressures
      compared to the IGFBP-3 complex and the control group. Correspondingly in the
      cavernosum, there were significantly more NOS-containing nerve fibers in the sham
      and IGF-1 groups. In conclusion, administration of IGF-1 can facilitate the
      regeneration of NOS-containing nerve fibers in penile tissue and enhance the
      recovery of erectile function after bilateral cavernous nerve cryoablation. The
      reverse effect was noted with the IGFBP-3 complex injection.

PMID- 14973526
TI  - Effects of sildenafil on ocular perfusion demonstrated by color Doppler
      ultrasonography.
AB  - The aim of this study was to investigate the effects of sildenafil on ocular
      hemodynamics by color Doppler ultrasonography (CDU). In all, 38 patients with
      erectile dysfunction diagnosed by International Index of Erectile Function (IIEF)
      and Sexual Health Inventory of Men (SHIM) scores were included into the study.
      After taking 100 mg of oral sildenafil citrate, all patients underwent CDU
      examination of central retinal artery at 60 and 75 min and CDU examination of
      cavernosal artery at 20, 60 and 75 min. All of the side effects during and after
      the test were also recorded. The mean cavernous artery peak systolic flow
      velocity increased significantly after sildenafil. However, no significant change
      was determined in central retinal artery flow parameters including peak systolic
      flow velocity, end-diastolic flow velocity, resistive index, pulsatility index,
      volume and diameter. Five patients experienced ocular side effects. No
      significant change was observed in retinal artery CDU measurements of patients
      having ocular side effects. Sildenafil has no effect on ocular hemodynamics on
      the basis of CDU. Ocular side effects may be the result of other changes in
      retinal photoreceptors rather than the ocular circulation.

PMID- 14973527
TI  - In vivo rat model to measure hypogastric nerve stimulation-induced seminal
      vesicle and vasal pressure responses simultaneously.
AB  - This study presents a modified in vivo model in which the intraluminal pressures
      of the seminal vesicle and vas deferens can be measured simultaneously. Male
      Sprague-Dawley rats were grouped based on agent administered: serotonin,
      clomipramine, fluoxetine, sertraline, paroxetine, prazosin, terazosin, and
      tamsulosin. The control responses to hypogastric nerve stimulation (HNS) were
      recorded in each animal, and HNS was repeated after each drug administration.
      Serotonergic agents resulted in concentration-dependent inhibition of the HNS
      induced seminal vesicle pressure increases
      (clomipramine>serotonin>fluoxetine>sertraline approximately paroxetine). On the
      other hand, only serotonin and clomipramine significantly inhibited vasal
      pressure responses. alpha-Adrenergic blockers inhibited both intraluminal
      pressure responses in a concentration-dependent manner. This model illustrates
      the importance of the hypogastric nerve for the stimulation of the seminal tract,
      with attention focused on the seminal vesicle. This model may be useful for the
      evaluation of drugs for the treatment of premature ejaculation.

PMID- 14973528
TI  - Therapeutic effects of colchicine in the management of Peyronie's disease: a
      randomized double-blind, placebo-controlled study.
AB  - To determine effectiveness and safety of colchicine in Peyronie's disease. In
      all, 84 patients with Peyronie's disease who did not have calcified plaque were
      entered into study. The mean disease duration was 15 months. A medical history
      was obtained, and physical examination, penile X-ray, and dynamic penile duplex
      ultrasound were performed. Patients were randomly divided into group 1, those who
      received 0.5-2.5 mg colchicine daily for 4 months and group 2, who received
      placebo for the same period. Response to therapy was assessed objectively, during
      dynamic penile duplex ultrasound, as well as subjectively using International
      Index of Erectile Function (IIEF) questionnaire and measurements of pain,
      duration of disease, penile curvature, and plaque size. Differences before and
      after treatment and among the three Kelami classification groups were assessed.
      In total, 78 (92.8%) completed the whole treatment schedule. Pain resolved in 60
      and 63.6% of the patients treated with colchicine and placebo, respectively (P >
      0.05). After therapy, in subjects and controls a reduction in the penile
      deformity was observed by 17.1 and 18.4% of the patients (P > 0.05), and a
      decrease in plaque size was noticed by 10.5 and 10%, respectively (P > 0.05).
      Objective measurements did not demonstrate any difference in plaque size or
      penile curvature. There were no substantial differences in response to treatment
      based on duration of disease or within the three Kelami classification groups.
      Significant drug-related adverse effects occurred in colchicine group and in two
      cases was treatment discontinued. Colchicine is no better than placebo in
      improvement of pain, curvature angle, or plaque size in patients with Peyronie's
      disease.

PMID- 14973529
TI  - Epidemiology of erectile dysfunction and its risk factors: a practice-based study
      in Denmark.
AB  - The objective of this study was to estimate the prevalence of erectile
      dysfunction (ED) and its health-related correlates among Danish men, to evaluate
      the influence of age, tobacco smoking, educational level and medication and the
      needs for treatment and willingness to be treated. A validated questionnaire was
      sent to 4310 noninstitutionalized Danish men, aged 40-80 y. The men selected
      constituted all male patients aged 40-80 y in 12 general practitioner practices
      in a county of Zealand, representing both the urban and rural population. Besides
      age, education, marital status and International Index of Erectile Function, the
      questionnaire included the duration of sexual problems (ED, premature
      ejaculation, penile curvature), comorbidity, medication, risk factors and the
      effect of prior treatment and willingness to seek treatment for sexual problems.
      A total of 2210 men responded, giving a response rate of 51.3%. No difference in
      the response rate by age groups was noted. The prevalence of complete ED
      increased with increasing age: 40-45 y, ED: 4.5%; 50-55 y, ED: 11.1%; and 75-80 y
      ED: 52%. The frequency of ED increased three-fold from men without comedication
      to men having some kind of medical treatment. Risk factors included tobacco
      smoking and low educational level. Only 9% suffering from ED had received some
      kind of treatment. Of the treated men, 75% were satisfied with the treatment.
      Willingness to discuss sexual matters depended both upon the age of the man and
      his actual erectile function. Taboos were seen more frequently among elderly
      people. ED increases with age, but only 10% of the men with sexual problems seek
      advice. Medication predisposes to ED.

PMID- 14973530
TI  - Peyronie's disease fibroblasts demonstrate tumorigenicity in the severe combined
      immunodeficient (SCID) mouse model.
AB  - Peyronie's disease is a localized connective tissue disorder, caused by trauma to
      the erect penis, which results in cellular proliferation and excess extracellular
      matrix production within the tunica albuginea of the penis. We have previously
      demonstrated that cells derived from Peyronie's disease plaque tissue demonstrate
      increased cell growth, increased S-phase on flow cytometry, stabilization and
      inactivation of p53, and consistent morphologic transformation, all suggesting
      that these cells are biologically transformed. Severe combined immunodeficient
      (SCID) mice have been used extensively to study the pathobiology of malignant and
      benign tissue and cells. This study was undertaken to determine if Peyronie's
      derived fibroblasts had the potential to demonstrate tumorigenicity in the SCID
      mouse model, thus confirming their biologically transformed nature. Cultured
      fibroblasts were derived from three sources, namely, plaque tissue excised from
      men with Peyronie's disease, tunical tissue excised from young men with
      congenital penile curvature and neonatal foreskins. BALB/C SCID mice were divided
      into three groups and each group was inoculated with cultured fibroblasts from
      each of the three different sources. All animals were evaluated regularly and
      maintained in isolation for a period of 3 months following inoculation. All SCID
      mice inoculated with cells derived from Peyronie's disease plaque tissue (n=10)
      developed subcutaneous nodules at a mean time period of 2.5+/-0.5 months
      following injection. The mean maximum dimension and weight of the nodules at the
      time of killing the animal was 1.1+/-0.2 cms and 0.6+/-0.2 g, respectively.
      Histologically, the nodules were composed of large pleomorphic epithelioid cells
      with a high mitotic activity, which were negative for cytokeratin but positive
      for vimentin. None of the SCID mice inoculated with cells cultured from either
      normal tunica (n=5) or foreskin (n=5) developed subcutaneous nodules. In
      conclusion, the tumorigenic nature of Peyronie's disease plaque-derived
      fibroblasts sheds further light on the pathobiologic characteristics of these
      cells. Specifically, these data confirm that cells cultured from Peyronie's
      disease plaque are biologically transformed. Future refinement and study of this
      animal model may permit a more complete understanding of the pathophysiology of
      Peyronie's disease and fibromatoses in general. Furthermore, such an animal model
      may, in the future, allow a more ready evaluation of the therapeutic
      interventions for Peyronie's disease.

PMID- 14973531
TI  - Cavernosometry: a theoretical analysis.
AB  - Erectile dysfunction may be caused by hormonal, neural, arterial, or venous
      factors. Cavernosometry is used to test for venous leaks. The outcome of surgical
      procedures attempting to block off veins that allow blood to leak from the penile
      tissues is still poor. This procedure commonly follows a diagnostic procedure
      based on cavernosometry after good arterial inflow has been established. To study
      the cavernosometry test, a mathematical model of penile hemodynamics was used to
      analyze the significance of its indications and its sensitivity to both arterial
      and venous factors. The model elucidates the mechanism of cavernosometry and
      shows that indeed this test is sensitive to venous factors and insensitive to
      arterial factors. The model also supports the use of supra-arterial pressure
      during cavernosometry, and the use of the slope of the flow-to-maintain vs
      maintained-pressure curve as an indicator of venous leak severity.

PMID- 14973532
TI  - Serum androgen levels in healthy premenopausal women with and without sexual
      dysfunction: Part B: Reduced serum androgen levels in healthy premenopausal women
      with complaints of sexual dysfunction.
AB  - Androgen insufficiency has been associated with decreased libido and arousal in
      postmenopausal women, but rarely has been evaluated in healthy premenopausal
      women. In all, 32 healthy premenopausal women were enrolled in this study, 18
      with one or more complaints of sexual dysfunction and 14 without. Assays of
      ovarian and adrenal androgens were measured before and after ACTH stimulation.
      The women with complaints of sexual dysfunction had significantly lower adrenal
      androgens than did the control women. There were no differences in the basal
      ovarian androgens or cortisol levels. After ACTH, both groups stimulated cortisol
      as well as adrenal and ovarian androgens. In conclusion, premenopausal women with
      complaints of sexual dysfunction had lower adrenal androgen precursors and
      testosterone than age-matched control women without such complaints. Further
      study is required to determine how lower adrenal androgens contribute to female
      sexual dysfunction.

PMID- 14973533
TI  - Use of oral ketoconazole to prevent postoperative erections following penile
      surgery.
AB  - Analgesics and topical agents ineffectively inhibit painful erections after
      penile and urethral surgery. Oral ketoconazole reversibly inhibits testosterone
      production and has been used empirically at our institution to decrease
      postoperative erections. We performed a retrospective review of 38 patients who
      had undergone penile and urethral reconstructive surgery. In all, 31 patients
      received 400 mg of ketoconazole three times daily for 10-14 days postoperatively
      (the study group) and seven patients did not receive ketoconazole (the control
      group). The incidence of postoperative erections, pain, side effects, surgical
      outcomes and patient satisfaction in each group were compared. Of the control
      group, 71% reported erections in the immediate postoperative period, and all
      these patients reported the erections were painful. Only 23% of the patient
      taking ketoconazole reported postoperative erections, and only 16% reported the
      erections were painful. We conclude that ketoconazole effectively prevents
      painful postoperative erections with minimal side effects.

PMID- 14973534
TI  - Impact of various questionnaires on the prevalence of erectile dysfunction. The
      ENIGMA-study.
AB  - The prevalence estimates of erectile dysfunction (ED) vary considerably across
      studies. These differences may be attributed to used definitions of ED.
      Quantitative data on the effect of different definitions of ED on the prevalence
      are lacking, because precise information on the used definition and questionnaire
      is often absent. Aim of this study was to quantify the effect of using different
      questionnaires for ED on the prevalence estimates. In all, 5721 mail surveys on
      sexual problems and ED were sent to all men (aged >18 y) in 12 general practices
      in the middle of the Netherlands of which 2117 were completed. The questionnaire
      contained Enigma (WHO), International Index of Erectile Function (IIEF), Cologne
      Erectile Inventory (KEED) and one question (Boxmeer, Krimpen). The prevalence of
      ED based on the various questionnaires and the effect of these questionnaires on
      risk factor relationships was compared. IIEF gave the highest age specific and
      overall ED prevalence, KEED the lowest. The difference in prevalence was 16.8%.
      The agreement (kappa coefficient) between the various ED definitions varied from
      0.52 (IIEF & KEED) to 0.95 (Enigma & Boxmeer). The number of risk factor
      relations were similar for the Dutch studies, reduced for the IIEF and KEED. This
      study provides evidence that differences in questionnaires to assess ED have a
      considerable effect on the (age specific) prevalence estimates and little on the
      risk factor relations. The number of questions of the survey appears not to be
      responsible for differences in the prevalence of ED and risk factor relations,
      however they affect the response rate. Uniform use is strongly recommended, since
      a 'golden standard' for ED assessment (by questionnaire) is lacking. A short
      questionnaire with one or two questions is recommended for example the one from
      the Boxmeer-study. These data may be used to adjust (age-specific) prevalence
      rates comparing ED prevalence in the open population across studies.

PMID- 14973535
TI  - Gene therapy: cornerstone of modern medicine in the new millennium?

PMID- 14973536
TI  - Unexpected pulmonary uptake of adenovirus vectors in animals with chronic liver
      disease.
AB  - When adenovirus vectors are injected intravenously, most of the virions are
      quickly taken up by the reticuloendothelial system, primarily by the liver
      macrophages known as Kupffer cells. However, little is known about the behavior
      of adenovirus vectors when there is pre-existing liver disease. To study this, we
      examined the biodistribution of intravenously injected vector in a rat model of
      cirrhosis induced by bile duct ligation. Using quantitative PCR and fluorescently
      tagged adenovirus vectors, we observed a significant reduction in vector uptake
      by the cirrhotic liver and increased accumulation in the lungs.
      Immunocytochemistry and electron microscopy demonstrated that this was due to
      changes in the reticuloendothelial system, with the vector being taken up by
      large numbers of pulmonary intravascular macrophages in the lungs of cirrhotic
      rats. Interestingly, expression of vector-encoded luciferase was significantly
      reduced in the livers of cirrhotic rats, but was not increased in the lungs.
      These data demonstrate that the biodistribution of adenovirus vectors in rats is
      altered by cirrhosis, which suggests the possibility that these vectors might
      behave unexpectedly in patients with pre-existing liver conditions, particularly
      since pulmonary reticuloendothelial changes are known to occur in human disease.

PMID- 14973537
TI  - Simple and effective osteoinductive gene therapy by local injection of a bone
      morphogenetic protein-2-expressing recombinant adenoviral vector and FK506
      mixture in rats.
AB  - We have previously utilized a human bone morphogenetic protein-2 (BMP-2)
      expressing recombinant adenoviral vector (AxCAOBMP-2) for osteoinductive gene
      therapy in rats. However, immunosuppression is essential for osteoinduction by
      AxCAOBMP-2 and this is one of the major impediments to its clinical use.
      Injection of AxCAOBMP-2 together with the immunosuppressant FK506 made it
      possible to markedly reduce the dose of the immunosuppressive agent and still
      induce ectopic bone reliably. We injected AxCAOBMP-2 and FK506 into the right
      calf muscle of rats, while the same number of plaque forming units of AxCAOBMP-2
      and the same dose of FK506 placebo (vehicle) were injected into the left calf
      muscle. At 1, 3, 5, 7, 9 days after injection, BMP-2 mRNA expression was
      significantly higher in the right calf muscle than in the left calf muscle. At 21
      days after injection, significantly more ectopic bone was observed in the right
      calf muscle than in the left calf muscle. These results indicate that coinjection
      of FK506 significantly promotes osteoinduction. In addition, local injection of
      FK506 may also make it possible to prevent a decrease of gene expression with
      other adenoviral vector.

PMID- 14973538
TI  - Reduced immunogenicity of DNA vaccine plasmids in mixtures.
AB  - We measured the ability of nine DNA vaccine plasmids encoding candidate malaria
      vaccine antigens to induce antibodies and interferon-gamma responses when
      delivered alone or in a mixture containing all nine plasmids. We further examined
      the possible immunosuppressive effect of individual plasmids, by assessing a
      series of mixtures in which each of the nine vaccine plasmids was replaced with a
      control plasmid. Given alone, each of the vaccine plasmids induced significant
      antibody titers and, in the four cases for which appropriate assays were
      available, IFN-gamma responses. Significant suppression or complete abrogation of
      responses were seen when the plasmids were pooled in a nine-plasmid cocktail and
      injected in a single site. Removal of single genes from the mixture frequently
      reduced the observed suppression. Boosting with recombinant poxvirus increased
      the antibody response in animals primed with either a single gene or the mixture,
      but, even after boosting, responses were higher in animals primed with single
      plasmids than in those primed with the nine-plasmid mixture. Boosting did not
      overcome the suppressive effect of mixing for IFN-gamma responses. Interactions
      between components in a multiplasmid DNA vaccine may limit the ability to use
      plasmid pools alone to induce responses against multiple targets simultaneously.

PMID- 14973539
TI  - Stable polyplexes based on arginine-containing oligopeptides for in vivo gene
      delivery.
AB  - In this study, we investigated to what extent the stability and transduction
      capacity of polyplexed DNA can be improved by optimizing the condensing peptide
      sequence. We have synthesized a small library of cationic peptides, at which the
      lysine/arginine ratio and the cation charge were varied. All peptides were able
      to compact DNA, at which polyplexes of short lysine-rich sequences were
      considerably larger than those of elongated or arginine-rich peptides (GM102 and
      GM202). In addition, the arginine-rich peptides GM102 and GM202 rendered the
      polyplexes resistant to plasma incubation or DNase I-mediated digestion. While
      all peptides were found to improve the transfection efficiency in HepG2 cells,
      only the GM102- and GM202-derived polyplexes could be specifically targeted to
      HepG2 cells by incorporation of a ligand-derivatized YKAK(8)WK peptide. We
      propose that GM102 and GM202 combine the advantage of small condensing peptides
      to give small-sized polyplexes with the superior stability of condensing
      polymers, which makes GM102 and GM202 excellent candidates for future in vivo
      gene therapy studies.

PMID- 14973540
TI  - Kinetics and characteristics of replication-competent revertants derived from
      self-inactivating foamy virus vectors.
AB  - In this study, self-inactivating (SIN) retroviral vectors based on feline foamy
      virus (FFV) were constructed and analysed. The FFV SIN vectors were devoid of the
      core FFV long terminal repeat promoter plus upstream sequences but contained all
      structural and regulatory genes. This design allowed sensitive detection of
      replication-competent revertants (RCRs). The FFV SIN vectors efficiently
      transduced the green fluorescence protein into recipient cells. However, RCRs
      appeared after serial passages of transduced cells. In all RCR clones analysed,
      parts of the heterologous cytomegalovirus immediate early promoter, originally
      driving expression of the FFV vector genome, were taken up to restore the deleted
      SIN promoter function required for replication competence. The RCRs were strongly
      reduced in replication capacity compared with the parental replication-competent
      vectors containing the FFV promoter. In all RCR genomes analysed, the uptake of
      the heterologous promoter was accompanied by deletion of almost the complete
      marker gene. Although the RCRs described in this study may not have the capacity
      to spread in humans and animals, they may pose a theoretical risk, for instance
      during transduction of haematopoietic stem cells. Thus, FV-based SIN vectors
      require additional genetic modifications in order to avoid RCRs.

PMID- 14973541
TI  - Erythrocyte ghost-mediated gene delivery for prolonged and blood-targeted
      expression.
AB  - This study reports the use of erythrocyte ghosts (EG) as a biocompatible nonviral
      delivery system for extended circulation and prolonged expression of plasmid DNA
      in the blood. Murine interleukin-2-expressing plasmid DNA was efficiently loaded
      to EG by electroporation in hypotonic condition. The presence of plasmid DNA in
      EG was confirmed by fluorescence-labeled plasmid DNA. At 21 min after intravenous
      administration into mice, the level of plasmid DNA in the blood was 92 000-fold
      higher following EG-mediated delivery as compared to the injection of naked form.
      EG-mediated gene delivery revealed higher and more prolonged mRNA expression
      levels of plasmid DNA in the blood until 9 days after the single intravenous
      injection. Moreover, plasmid DNA-loaded EG showed gene expression targeted to the
      blood cells. At 3 days post-dose, substantial expression levels of plasmid DNA
      delivered in EG were observed only in the blood and not in the other organs. Of
      the blood cells, the subpopulation containing granulocytes showed higher
      expression of plasmid DNA than mononuclear cells. These results indicate the
      potential of EG as a safe, prolonged and blood-targeted delivery system of
      therapeutic genes.

PMID- 14973542
TI  - Mechanism of improved gene transfer by the N-terminal stearylation of
      octaarginine: enhanced cellular association by hydrophobic core formation.
AB  - The internalization mechanisms associated with octaarginine and stearyl
      octaarginine were investigated using confocal laser microscopy and flow
      cytometric analysis. Octaarginine is able to translocate through cell membranes
      in a manner that does not exactly involve the classical endocytic pathways of
      internalization. However, when a stearyl moiety is attached to the N-terminus of
      octaarginine, the internalization shifts mainly to an endocytosis-dependent
      pathway. The transfection efficiency of stearyl-octaarginine was significantly
      higher than that of octaarginin. To understand the mechanism of the improved gene
      transfer by the N-terminal stearylation of octaarginine, the gene transfer
      processes mediated by octaarginine or stearyl-octaarginine were compared. Both
      octaarginine and stearyl-octaarginine are able to carry plasmid DNA into cells.
      The amount of plasmid DNA internalized as well as that delivered to the nucleus
      was higher in the case of stearyl-octaarginine. Even though the internalization
      mechanisms of octaarginine and stearyl-octaarginine were different, their
      complexes with plasmid DNA were internalized via the same pathway, presumably,
      the clathrin-mediated pathway of endocytosis. The results of the atomic force
      microscopy revealed that stearyl-octaarginine, but not octaarginine, can
      completely condense the DNA into stable complexes that can be highly adsorbed to
      the cell surface and subsequently highly internalized. Therefore, using
      stearylated-octaarginine provided higher internalization of plasmid DNA into
      cells, due to enhanced cellular association, as well as higher nuclear delivery.
      The results presented in this study provide a better understanding of the
      mechanisms of improved transfection using stearylated-octaarginine. The concept
      of using stearylated peptides may aid in the development of more efficient
      nonviral gene vectors.

PMID- 14973543
TI  - An inflammation-inducible adenoviral expression system for local treatment of the
      arthritic joint.
AB  - To achieve a disease-regulated transgene expression for physiologically
      responsive gene therapy of arthritis, a hybrid promoter was constructed. The
      human IL-1 beta enhancer region (-3690 to -2720) upstream of the human IL-6
      promoter region (-163 to +12) was essential in mounting a robust response in HIG
      82 synovial fibroblasts and in RAW 264,7 macrophages. A replication-deficient
      adenovirus was engineered with luciferase (Luc) controlled by the IL-1/IL-6
      promoter (Ad5.IL-1/IL-6-Luc). LPS caused a 23- and 4.6-fold induction of Luc.
      activity in RAW cells infected with Ad5.IL-1/IL-6-Luc or the conventional Ad5.CMV
      Luc construct, respectively. Next, adenoviruses (10(6) ffu) were injected into
      the knees of C57Bl/6 mice. An intra-articular injection of zymosan, 3 days after
      Ad5.IL-1/IL-6-Luc, increased Luc. activity by 39-fold but had no effect in the
      Ad5.CMV-Luc joints. The constitutive CMV promoter was rapidly silenced and could
      not be reactivated in vivo. In contrast, the IL-1/IL-6 promoter could be
      reactivated by Streptococcal cell wall (SCW)-induced arthritis up to 21 days
      after infection. Next the IL-1/IL-6 promoter was compared to the C3-Tat/HIV-LTR
      two-component system in wild-type, IL-6(-/-) and IL-1(-/-) gene knockout mice.
      Both systems responded well to LPS-, zymosan- and SCW-induced arthritis. However,
      the basal activity of the IL-1/IL-6 promoter was lower and IL-6 independent. This
      study showed that the IL-1/IL-6 promoter is feasible to achieve disease-regulated
      transgene expression for treatment of arthritis.

PMID- 14973544
TI  - DNA vaccine-encapsulated virus-like particles derived from an orally
      transmissible virus stimulate mucosal and systemic immune responses by oral
      administration.
AB  - Delivery of foreign genes to the digestive tract mucosa by oral administration of
      nonreplicating gene transfer vectors would be a very useful method for
      vaccination and gene therapy. However, there have been few reports on suitable
      vectors. In the present study, we found that plasmid DNA can be packaged in vitro
      into a virus-like particle (VLP) composed of open reading frame 2 of hepatitis E
      virus, which is an orally transmissible virus, and that these VLPs can deliver
      this foreign DNA to the intestinal mucosa in vivo. The delivery of plasmid DNA to
      the mucosa of the small intestine was confirmed by the results of
      immunohistochemical analyses using an expression plasmid encoding human
      immunodeficiency virus env (HIV env) gp120. After oral administration of VLPs
      loaded with HIV env cDNA, significant levels of specific IgG and IgA to HIV env
      in fecal extracts and sera were found. Moreover, mice used in this study
      exhibited cytotoxic T-lymphocyte responses specific to HIV env in the spleen,
      Payer's patches and mesenteric lymph nodes. These findings suggest that VLPs
      derived from orally transmissible viruses can be used as vectors for delivery of
      genes to mucosal tissue by oral administration for the purpose of DNA vaccination
      and gene therapy.

PMID- 14973545
TI  - Induction of long-term cardiac allograft survival by heme oxygenase-1 gene
      transfer.
AB  - Elevated expression of heme oxygenase-1 (HO-1), an intracellular enzyme that
      degrades heme into carbon monoxide (CO), biliverdine and free iron, has anti
      inflammatory and antiapoptotic effects in diverse models. Here, we analyzed the
      effects of specific overexpression of HO-1 following adenovirus-mediated (AdHO-1)
      gene transfer in an acute cardiac allograft rejection model. The intragraft
      (i.g.) injection of AdHO-1 into cardiac allografts, as well as intramuscular
      (i.m.) or intravenous (i.v.) administration, prolonged allograft survival with,
      respectively, 13.3, 62.5 and 80% of the grafts surviving long term (>100 days),
      whereas control grafts were rejected with acute kinetics. HO-1 overexpression was
      associated with inhibited allogeneic responses in MLRs using graft-infiltrating
      leukocytes and splenocytes, but not with lymph node cells. The inhibition of
      splenocyte proliferation was mediated by soluble factors and was dependent on the
      presence of APCs, since purified T cells proliferated normally. i.v. but not i.g.
      AdHO-1 administration decreased the number of graft-infiltrating leukocytes,
      cytokine mRNA accumulation and apoptosis in transplanted hearts, whereas i.v. and
      i.g. AdHO-1 did not modify normal immune responses against cognate antigens,
      indicating that there was no general immunosuppression. These results indicate
      that HO-1 overexpression prolongs the survival of vascularized allografts by
      promoting tolerogenic mechanisms acting on allogeneic cellular immune responses.

PMID- 14973546
TI  - Premature stop codons involved in muscular dystrophies show a broad spectrum of
      readthrough efficiencies in response to gentamicin treatment.
AB  - The suppression levels induced by gentamicin on premature stop codons, caused by
      primary nonsense mutations found in muscular dystrophy patients, were assessed
      using a very sensitive dual reporter gene assay. Results show that: (i) the
      effect of gentamicin on readthrough is similar in cultured cells and in vivo in
      murine skeletal muscle; (ii) a wide variability of readthrough efficiency is
      obtained, depending on the mutation tested; (iii) due to the complexity of
      readthrough regulation, efficiency cannot be predicted by the nucleotide context
      of the stop codon; (iv) only a minority of premature stop codons found in
      patients show a significant level of readthrough, and would thus be amenable to
      this pharmacological treatment, given our present understanding of the problem.
      These results probably provide an explanation for the relative failure of
      clinical trials reported to date using gentamicin to treat diseases due to
      premature stop codons, and emphasize that preliminary assays in cell culture
      provide valuable information concerning the potential efficiency of
      pharmacological treatments.

PMID- 14973547
TI  - Enhanced apoptosis following treatment with TRA-8 anti-human DR5 monoclonal
      antibody and overexpression of exogenous Bax in human glioma cells.
AB  - Specific activation of apoptosis in tumor cells offers a promising approach for
      cancer therapy. Induction of apoptosis leads to activation of specific proteases.
      Two major pathways for caspase activation in mammalian cells have been described.
      One apoptotic pathway involves members of the tumor necrosis factor family of
      cytokine receptors (eg death receptor 5 (DR5)). The other pathway is controlled
      by the Bcl-2 family of proteins. The purpose of this study was to investigate
      whether increased apoptosis occurs in human glioma cells following infection with
      a recombinant adenoviral vector encoding the human Bax gene under the control of
      human vascular endothelial growth factor (VEGF) promoter element (AdVEGFBax) in
      combination with an anti-human DR5 monoclonal antibody (TRA-8). Specific
      overexpression of exogenous Bax protein induced apoptosis and cell death in
      glioma cell lines, through activation of both caspase-8 and -9, leading to
      activation of downstream caspase-3. The relative sensitivity to AdVEGFBax for the
      glioma cell lines was U251MG>U373MG>U87MG>D54MG. The recently characterized TRA-8
      monoclonal antibody induces apoptosis of most TRAIL-sensitive tumor cells by
      specific binding to DR5 receptors on the cellular membrane. TRA-8 induced rapid
      apoptosis and cell death in glioma cells, but did not demonstrate detectable
      cytotoxicity of primary normal human astrocytes. The efficiency of TRA-8-induced
      apoptosis was variable in different glioma cell lines. The relative sensitivity
      to TRA-8 was U373MG>U87MG>U251MG>D54MG. The combination of TRA-8 treatment and
      overexpression of Bax overcame TRA-8 resistance of glioma cells in vitro. Cell
      viability of U251MG cells was 71.1% for TRA-8 (100 ng/ml) alone, 75.9% for
      AdVEGFBax (5 MOI) alone and 41.1% for their combination as measured by MTS assay.
      Similar enhanced apoptosis results were obtained for the other glioma cell lines.
      In vivo studies demonstrated that the combined treatment significantly (P<0.05)
      suppressed the growth of U251MG xenografts and produced 60% complete tumor
      regressions without recurrence. These data suggest that the combination of TRA-8
      treatment with specific overexpression of Bax using AdVEGFBax may be an effective
      approach for the treatment of human malignant gliomas.

PMID- 14973548
TI  - Is there a future for TNF promoter polymorphisms?
AB  - The in vitro study of TNF promoter polymorphism (SNP) function was stimulated by
      the numerous case-control (association) studies of the polymorphisms in relation
      to human disease and the appearance of several studies claiming to show a
      functional role for these SNPs provided a further impetus to researchers
      interested in the role of TNF in their disease of interest. In this review we
      consider case-control studies, concentrating on the autoimmune and inflammatory
      diseases rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and
      asthma, and on infectious diseases including malaria, hepatitis B and C
      infection, leprosy and sepsis/septic shock. We also review the available evidence
      on the functional role of the various TNF promoter polymorphisms. In general,
      case-control studies have produced mixed results, with little consensus in most
      cases on whether any TNF polymorphisms are actually associated with disease,
      although results have been more consistent in the case of infectious diseases,
      particularly malaria. Functional studies have also produced mixed results but
      recent work suggests that the much studied -308G/A polymorphism is not
      functional, while the function of other TNF polymorphisms remains controversial.
      Studies of the TNF region are increasingly using extended haplotypes that can
      better capture the variation of the MHC region.

PMID- 14973549
TI  - Treatment of bladder carcinomas using recombinant BCG DNA vaccines and
      electroporative gene immunotherapy.
AB  - Intravesical immunotherapy with live Mycobacterium bovis bacillus Calmette-Guerin
      (BCG) is the treatment of choice for superficial bladder cancers. Nevertheless, a
      significant proportion of patients do not respond to this therapy, and adverse
      effects are common. Here, we report the cloning of recombinant mycobacterial DNA
      vaccines and demonstrate the ability of multicomponent and multisubunit DNA
      vaccines to enhance Th1-polarized cytokine-mediated responses as well as effector
      cell responses. Splenocytes from immunized groups of mice were restimulated in
      vitro and examined for cytotoxicity against murine bladder tumur (MBT-2) cells.
      We used four combined recombinant BCG DNA vaccines (poly-rBCG) for
      electroporative gene immunotherapy (EPGIT) in vivo, and found that tumor growth
      was significantly inhibited and mouse survival was prolonged. Increased immune
      cell infiltration and induction of apoptosis were noted after treatment with poly
      rBCG alone, with the murine interleukin-12 (mIL-12) vaccine alone, and-most
      significantly-with the poly-rBCG+mIL-12 vaccine combination. Electroporation of
      poly-rBCG+mIL-12 resulted in complete tumor eradication in seven of eight mice
      (P<.01) within 28 days. Thus, EPGIT using multicomponent multisubunit BCG is
      highly effective in the treatment of bladder cancer. This approach presents new
      possibilities for the treatment of bladder cancer using recombinant BCG DNA
      vaccines.

PMID- 14973550
TI  - Gene expression profiling of colon cancer by DNA microarrays and correlation with
      histoclinical parameters.
AB  - Different diagnostic and prognostic groups of colorectal carcinoma (CRC) have
      been defined. However, accurate diagnosis and prediction of survival are
      sometimes difficult. Gene expression profiling might improve these
      classifications and bring new insights into underlying molecular mechanisms. We
      profiled 50 cancerous and noncancerous colon tissues using DNA microarrrays
      consisting of approximately 8000 spotted human cDNA. Global hierarchical
      clustering was to some extent able to distinguish clinically relevant subgroups,
      normal versus cancer tissues and metastatic versus nonmetastatic tumours.
      Supervised analyses improved these segregations by identifying sets of genes that
      discriminated between normal and tumour tissues, tumours associated or not with
      lymph node invasion or genetic instability, and tumours from the right or left
      colon. A similar approach identified a gene set that divided patients with
      significantly different 5-year survival (100% in one group and 40% in the other
      group; P=0.005). Discriminator genes were associated with various cellular
      processes. An immunohistochemical study on 382 tumour and normal samples
      deposited onto a tissue microarray subsequently validated the upregulation of
      NM23 in CRC and a downregulation in poor prognosis tumours. These results suggest
      that microarrays may provide means to improve the classification of CRC, provide
      new potential targets against carcinogenesis and new diagnostic and/or prognostic
      markers and therapeutic targets.

PMID- 14973551
TI  - The cooperation of B-Myb with the coactivator p300 is orchestrated by cyclins A
      and D1.
AB  - B-Myb is a highly conserved member of the Myb family of transcription factors
      whose activity is regulated during the cell cycle. Previous work has shown that
      the activity of B-Myb is stimulated by cyclin A/Cdk2-dependent phosphorylation
      whereas interaction of B-Myb with cyclin D1 inhibits its activity. Here, we have
      investigated the role of p300 as a coactivator for B-Myb. We show that B-Myb
      dependent transactivation is stimulated by p300 as a result of interaction
      between B-Myb and p300. We have mapped the sequences responsible for the
      interaction of B-Myb and p300 to the E1A-binding region of p300 and the
      transactivation domain of B-Myb, respectively. Furthermore, our data suggest that
      phosphorylation of B-Myb stimulates its acetylation by p300 and that the
      acetylation of B-Myb is necessary for the full stimulation of its transactivation
      potential by p300. We have also studied the effect of cyclin D1 on the
      cooperation of B-Myb and p300. Based on our results we propose that cyclin D1
      inhibits the activity of B-Myb by interfering with the interaction of B-Myb and
      p300. The data reported here provide novel insight into the mechanisms by which
      the activity of B-Myb is regulated during the cell cycle. Taken together they
      suggest that the coactivator p300 plays an important role in this regulation and
      that the cooperation of B-Myb and p300 is orchestrated by cyclins A and D1.

PMID- 14973552
TI  - Gene expression profiling of ErbB receptor and ligand-dependent transcription.
AB  - Overexpression of ErbB2 and ErbB4 receptors in breast cancers may be accompanied
      by contrasting clinical outcomes. To investigate the molecular mechanisms
      contributing to these differences, we undertook a comparative study of gene
      expression regulated by the two receptors. Agonistic antibodies were employed to
      activate ErbB2 and ErbB4 in isolation from the other ErbBs in breast cancer
      cells. Gene expression profiling using a 16 755-gene oligonucleotide array was
      performed to identify transcriptional targets of receptor activation. Our results
      indicate that, in the same cell line, ErbB2 and ErbB4 activation influence gene
      transcription differentially. Although there are genes that are regulated by
      signaling from both receptors, there are also receptor-specific targets that are
      preferentially regulated by each receptor. We further show that two ligands
      acting via the same receptor homodimer may activate different subsets of genes.
      Many of the induced genes are hitherto unidentified targets of ErbB signaling.
      These include ErbB4 targets EPS15R, GATA4, and RAB2 and ErbB2-activated HRY/HES1
      and PPAP2A. Targets of ErbB2 homodimer signaling may be especially important as
      markers in breast cancer, where ErbB2 homodimerization mediated by overexpression
      and ligand-independent activation is common.

PMID- 14973553
TI  - HSulf-1 modulates HGF-mediated tumor cell invasion and signaling in head and neck
      squamous carcinoma.
AB  - Recently, we cloned a novel sulfatase domain-containing downregulated gene, HSulf
      1, which modulates heparin-binding growth factor signaling in ovarian cancer.
      Based on the pilot data showing the loss of HSulf-1 in head and neck squamous
      cell carcinoma cell lines (SCCHN), we sought to employ SCCHN as a model to define
      the role of HSulf-1 in the molecular regulation of tumorigenicity. Three SCCHN
      lines (012SCC, WMMSCC, and 015SCC) had no detectable HSulf-1 mRNA. Clonal lines
      of HSulf-1-expressing 012SCC attenuated the activation of ERK/mitogen-activated
      protein kinase (MAPK) signaling mediated by fibroblast growth factor (FGF-2) and
      both ERK/MAPK and Akt signaling mediated by hepatocyte growth factor (HGF).
      Consistent with this downregulation, phosphorylation of HGF receptor, c-Met,
      which is frequently overexpressed in SCCHN, was also attenuated in HSulf-1 clonal
      012SCC cell lines. HGF markedly enhanced the motility and migration of vector
      transfected cells in a transwell invasion chamber. However, HGF-mediated motility
      and invasion was attenuated in HSulf-1 clonal 012SCC cell lines. In addition,
      transfected cells displayed significant growth inhibition concomitant with a
      decrease in mitogenicity, as measured by thymidine incorporation and increased
      sensitivity to staurosporine- and cisplatin-induced apoptosis. These data suggest
      that HSulf-1 normally functions as a negative regulator in cell growth and loss
      of HSulf-1 in SCCHN potentiates growth factor signaling, enhances motility,
      invasiveness and inhibits stress-induced apoptosis, with a resulting increase in
      tumorigenicity.

PMID- 14973554
TI  - EphA2: a determinant of malignant cellular behavior and a potential therapeutic
      target in pancreatic adenocarcinoma.
AB  - The EphA2 receptor tyrosine kinase is overexpressed in a variety of human
      cancers. We sought to characterize the role of EphA2 in pancreatic adenocarcinoma
      and, using RNA interference (RNAi) mediated by small interfering RNA (siRNA), we
      determined the effects of suppressing EphA2 expression in vitro and in vivo.
      EphA2 expression in PANC1, MIAPaCa2, BxPC3 and Capan2 cells was assessed by
      Northern and Western blot. We artificially overexpressed EphA2 by transient
      transfection and suppressed EphA2 expression using RNAi. Cellular invasiveness
      was quantified by modified Boyden chamber assay. Anoikis was induced by anchorage
      independent polyHEMA culture and caspase 3 activity was quantified
      fluorometrically. Focal adhesion kinase (FAK) phosphorylation was assessed by
      immunoprecipitation. EphA2 siRNA treatment was assessed in a nude mouse xenograft
      model. Pancreatic adenocarcinoma cells differentially express EphA2. Inherent and
      induced EphA2 overexpression is associated with increased cellular invasiveness
      and anoikis resistance. EphA2 siRNA suppresses EphA2 expression, cellular
      invasiveness, anoikis resistance and FAK phosphorylation in vitro and retards
      tumor growth and inhibits metastasis in vivo. EphA2 is both a determinant of
      malignant cellular behavior and a potential therapeutic target in pancreatic
      adenocarcinoma.

PMID- 14973555
TI  - CLCA2 tumour suppressor gene in 1p31 is epigenetically regulated in breast
      cancer.
AB  - The calcium-activated chloride channel gene family is clustered in the 1p31
      region, which is frequently deleted in sporadic breast cancer. Recent studies
      have indicated the association of the second member of this gene family (CLCA2)
      with the development of breast cancer and metastasis. We have now shown the
      absence of expression of CLCA2 in several breast cancer tumours and cell lines,
      which confirms the results from other reports. When overexpressed in CLCA2
      negative cell lines, their tumorigenicity and metastasis capability were
      significantly reduced, suggesting a tumour suppressor role for CLCA2 in breast
      cancer. The mechanisms behind the silencing of CLCA2 in breast cancer, however,
      have not been elucidated to date. Although we were able to identify CLCA2
      mutations in breast cancers, somatic mutations are not the major cause of CLCA2
      gene silencing. On the other hand, treatment of breast cancer CLCA2-negative cell
      lines with demethylating agents was able to restore CLCA2 expression, suggesting
      an epigenetic inactivation of this gene. Bisulphite-sequencing of the promoter
      associated CpG island of the CLCA2 gene in breast tumours demonstrated that the
      absence of expression in these tumours was caused by hypermethylation of the
      promoter CpG island. In contrast, in breast cancer cell lines, tumours, and
      control cell lines that express CLCA2, a much lower level, and often absence, of
      methylation of the promoter were demonstrated. These findings demonstrate that
      CLCA2 is frequently inactivated in breast cancer by promoter region
      hypermethylation, which makes it an excellent candidate for the 1p31 breast
      cancer tumour suppressor gene.

PMID- 14973556
TI  - Professional vital bleaching using a thin and concentrated peroxide gel on
      whitening strips: an integrated clinical summary.
AB  - Rapid innovation in vital bleaching continues to expand the number of treatment
      options available to patients, particularly in the area of at-home whitening. The
      development of bleaching strips represented a new paradigm in the delivery of
      peroxide. The efficacy and safety of bleaching strip systems delivering up to
      6.5% hydrogen peroxide has been established in numerous randomized clinical
      trials. In 2003, a novel bleaching strip with 14% hydrogen peroxide (Crest
      Whitestrips Supreme) was introduced. This advanced system carries a thinner but
      more concentrated gel on each strip, resulting in a relatively similar total
      amount of peroxide as compared to other strip systems. This 2-variable change,
      higher concentration gel with lowered gel volume translates to improved whitening
      without adversely affecting oral soft tissue tolerability and irritation. This
      paper provides an integrated review of 9 comparative clinical trials evaluating
      the whitening response (six trials) and safety (nine trials) of this novel vital
      bleaching system. Efficacy results for the 14% hydrogen peroxide strips were
      significantly (p<0.05) better than the placebo or pooled positive controls
      evaluated in the clinical trials assessing tooth color or shade. Adverse events
      were similar in type to the other vital bleaching systems. Overall, the research
      of 408 patients showed generally better efficacy and similar to or better
      tolerability for the 14% hydrogen peroxide strips compared to a selected group of
      marketed positive bleaching controls.

PMID- 14973557
TI  - Remineralization potential of a new toothpaste formulation: an in vitro study.
AB  - The aim of the present study was to determine the ability of a dentifrice
      containing a mixture of ion-exchange resins (named NMTD), which supplies calcium,
      fluoride, phosphate, and zinc ions, to promote remineralization and/or inhibit
      demineralization of dental human enamel in a pH cycling model in vitro. A
      fluoride toothpaste was used as the control. The enamel specimens were tested for
      microhardness before and after 10 days and 16 days of the demineralizing and
      remineralizing treatments. The results of this study showed both dentifrices were
      effective in limiting in vitro enamel demineralization although the effects were
      not significantly different from each other. Inclusion of calcium and phosphate
      ion-exchange resins in the dentifrice containing a fluoride ion-exchange resin
      maintained a similar net outcome of the conventional dentifrice in the
      demineralization/remineralization process under the experimental conditions
      employed.

PMID- 14973558
TI  - Medical health and medication use in elderly dental patients.
AB  - The objectives of this study were to obtain information on the medical conditions
      and medications used among elderly Thai dental patients and to investigate the
      relationship between the findings in relation to age and sex. The information
      regarding medical conditions and medication use was obtained from interviews of
      510 dental patients aged 60 years and older. The incidence of medical conditions
      was 82.5%; women had a significantly higher incidence of medical conditions
      (86.5%) than men (76.5%). The incidence of medical conditions did not differ
      among the three age groups. Overall, cardiovascular disease was the leading
      problem (33.7%) with hypertension being the major component (26.1%). The
      prevalent problems were bone/joint disorders (32.4%), allergies (18.2%), diabetes
      mellitus (14.5%), and eye and ear problems (14.3%). In our sample, 65.5% reported
      taking medications, with an average of 1.5 drug groups per person. The average
      number of medications taken increased as age increased. Women took medications
      more frequently than men (70% vs. 58.5%). The four most prevalent drugs were
      cardiovascular agents (32%), endocrinologic drugs (14.5%), nutritional
      therapeutics (12.9%), and drugs acting on the musculoskeletal system (11.4%). The
      present study supports the findings of previous reports in that the presence of
      medical conditions is high in the elderly and the incidence of medication use
      increases with advancing age.

PMID- 14973559
TI  - The bilateral occurrence of dental caries among 12-13 and 15-19 year old school
      children.
AB  - The purpose of the study was to determine the bilateral occurrence of dental
      caries in 12-13 year old and 15-19 year old Saudi school children. There were 673
      children (324 boys and 349 girls) in the 12-13 year old group and 734 children
      (399 boys and 335 girls) in the 15-19 year old group with mean ages of 13.1 (SD
      0.7) years and 16.4 (SD 1.2) years, respectively. All children were examined for
      dental caries using the World Health Organization (WHO) criteria for the
      diagnosis of dental caries. There were no significant differences between the
      caries prevalence of right and left sides for most teeth at the significance
      level of 0.05. Among 12-13 year old children, maxillary first molars (86.5%),
      mandibular central incisors (86.2%), and mandibular first molars (86.0%) showed
      very high (p <.01) caries bilaterality. Among the 15-19 year old children,
      mandibular first molars (91.6%), maxillary first molars (87.9%), and mandibular
      second molars (79.9%) showed very high (p <.01) caries bilaterality. The
      conditional probability for bilateral occurrence of caries was highest in first
      molars followed by second molars and central incisors. The bilateral caries
      occurrence and conditional probability for bilateral caries occurrence were
      significantly higher (p <.05) in 15-19 year old children as compared to 12-13
      year old children. It was concluded caries bilaterality and the conditional
      probability for bilateral caries occurrence was high in the study population.

PMID- 14973560
TI  - The visible portion of anterior teeth at rest.
AB  - The visibility of anterior tooth surfaces with lips at rest or during function is
      an important factor in determining prosthodontic outcome. There is a lack of
      sufficient information published on this subject. The aim of this study was to
      investigate the degree of visibility of maxillary and mandibular anterior teeth
      surfaces when the lips are at rest. Four hundred seventy three adults were
      examined. All the subjects had maxillary and mandibular anterior teeth present
      with no caries, restorations, severe attrition, mobility, extrusion, or obvious
      deformities. The portions of anterior teeth that were visible were measured
      vertically using a Boley gauge from the border of the lip to the incisal edge for
      the incisors and to the cusp tip for the canines. The measurement was taken at
      the midpoint of the tooth when the lips and lower jaw were at the rest position.
      The length of the upper lip was measured from the base of the columella to the
      tip of the philtrum at the midline of the face. Males showed more of the
      maxillary lateral, canine, and mandibular anterior teeth than females. With
      increasing age, the amount of maxillary anterior teeth that was visible at rest
      decreased. The subjects with shorter upper lips displayed more maxillary central
      incisor structure than those with longer upper lips. Racial differences were not
      found. The amount of visible portions of anterior teeth is determined by muscle
      positions that vary from person to another. It provides an excellent starting
      point for vertical positioning anterior teeth that can be modified as necessary
      in any clinical situation. The findings of this study should help the dentist in
      providing aesthetic prosthodontic treatment that involves replacement of anterior
      teeth. A useful guideline for positioning anterior teeth is suggested.

PMID- 14973561
TI  - Shear bond strengths and microleakage of four types of dentin adhesive materials.
AB  - The aim of this investigation was to compare the microleakage of composite resin
      (Z-100) and shear bond strength to bovine dentin using different types of
      adhesive systems (Scotch Bond Multi-Purpose, All-Bond 2, One-Step, and Perma
      Quick) to compare and correlate microleakage to shear bond strength. For the
      microleakage aspect of the study, 20 class V were prepared (bovine incisors) with
      90-degree cavosurface margins and were located at the cemento-enamel junction
      using a template. Each dentin bonding system was applied to five cavities
      following the manufacturer's instructions and restored with Z-100 composite
      resin. After 24 hours of storage in distilled water at 37 degrees C, the teeth
      were immersed in 2% basic fuchsin dye. All teeth were sectioned in a mesiodistal
      direction using a diamond saw, and each section was then inspected under a
      stereomacroscope. For the shear bond strength aspect of the study, 20 bovine
      incisors were centrally horizontally mounted in Teflon mold with cold cure
      acrylic resin. Flat labial dentin surfaces were prepared using different grit
      silicon carbide abrasive wheels. Five specimens were used for each of the bonding
      agent systems. Each specimen was bonded with restorative composite resin (Z-100)
      and applied to the treated dentinal surface through a split Teflon mold. All
      specimens were stored in distilled water at 37 degrees C for 24 hours. The bonds
      were stressed using shear forces at a crosshead speed of 0.5mm/min using an
      Instron Universal testing machine. Findings indicate none of the systems tested
      in this study were free from microleakage. Scotch bond multi-purpose achieved the
      best seal, with One-Step being second best, while All-Bond 2 and Perma Quick had
      the poorest seal. However, there were significant differences among the shear
      bond strengths of the four bonding systems tested. Scotch Bond Multi-Purpose has
      a higher bond strength to composite resin when compared to the other dentin
      adhesives. The study also concluded there is no association between microleakage
      and shear bond strength.

PMID- 14973562
TI  - Photoelastic study of the effects of occlusal surface morphology on tooth apical
      stress from vertical bite forces.
AB  - The aim of the study was to determine how the morphology of occlusal surfaces
      might affect occlusal loading that is transferred to the tooth apex. Photoelastic
      methods were used to assess apical stress generated by seven variations of
      occlusions. A test assembly with a 2 kg weight was applied to teeth to create a
      vertical load. By analyzing the direction and magnitude of the apical principle
      stress under the polar light that was measured at the apexes of mandibular teeth,
      the occlusal loading position of each tooth and its direction was obtained based
      on general mechanical principles. It was found distal incline planes (or slopes)
      of cusps and lingual incline planes (or slope) of buccal cusps of mandibular
      posterior teeth carried the greatest occlusal load in normal occlusion. In the
      other six variations of occlusion presented in this study, the principle apical
      stresses changed more or less as a result of the different occlusal contact
      relationships. The magnitude of principle apical stress increased considerably in
      the flat surface occlusion because of the lack of distribution of occlusion
      loading by the smooth dentition surface. It is concluded the occlusal surface
      morphology has a significant effect on the direction and magnitude of apical
      stress. To establish a suitable relationship of occlusion that can conduct
      favorable occlusal loading physiologically is very important.

PMID- 14973563
TI  - Nuclear medicine in oral and maxillofacial diagnosis: a review for the practicing
      dental professional.
AB  - Nuclear medicine studies often play a significant role in the diagnosis and
      treatment of oral and maxillofacial diseases. While not commonly used in everyday
      dental practice, the dental provider should have a conversational knowledge of
      these imaging modalities and understand the indications and limitations of these
      studies. The purpose of this review is to discuss the nuclear medicine studies
      that have applications in the head and neck region as well as their indications,
      limitations, and diagnostic conclusions that can be drawn from these studies.

PMID- 14973564
TI  - The immediate antimicrobial effect of a toothbrush and miswak on cariogenic
      bacteria: a clinical study.
AB  - The aim of this study was to assess the antimicrobial activity of the miswak
      chewing stick (Salvadora persica) in vivo, especially on streptococcus mutans and
      lactobacilli. The study was conducted clinically using patients' saliva and
      measuring the effect of miswak (chewing stick), miswak extract, toothbrush, and
      normal saline on mutans and lactobacilli. Forty male subjects aged 20-45 years
      were included in the study; there were four groups of ten subjects each. For the
      study, 50% of miswak extract (solution) was used. The levels of mutans
      streptococci and lactobacilli were measured using commercially available Vivacare
      line CRT (Caries Risk Test) bacteria 2 in 1 kit. The results showed there was a
      marked reduction of streptococcus mutans among all groups. When the groups were
      compared, the reduction of streptococcus mutans was significantly greater using
      miswak in comparison to toothbrushing (p = 0.013), and there was no significant
      difference for lactobacilli reduction (p = 0.147). It may be concluded miswak has
      an immediate antimicrobial effect. Streptococcus mutans were more susceptible to
      miswak antimicrobial activity than lactobacilli. Dietary intake of sugar and oral
      health status may be considered for controlled clinical trials with special
      emphasis on the antibacterial activity of miswak on cariogenic bacteria for a
      longer period of time. A toothbrush with and without toothpaste should be
      compared with miswak alone. Further research is needed with a larger sample size.

PMID- 14973565
TI  - Influence of passive ultrasonic activation on the penetration depth of different
      sealers.
AB  - Correct use of instruments and irrigating solutions are major factors during
      chemo-mechanical preparation of root canals. Ultrasonically activated files and
      solutions are used for debridement of canals. In this study 42 single rooted
      anterior human teeth were used. The roots were divided into two groups. One group
      received an application of 17% ethylenediamine tetra acetic acid (EDTA) of 1 ml
      for 1 min using an ultrasonically energized file. The other group received an
      application of 17% EDTA of 1 ml for 0.5 min using an ultrasonically energized
      file. The groups were divided again into two subgroups. The roots were filled
      with a resin based sealer, AH26 and a glass ionomer sealer--Endion with lateral
      condensation technique. The roots were separated into two halves. The specimens
      were viewed through a scanning electron microscope (SEM). Statistical differences
      between the groups and regions were analyzed with Variance and Duncan tests.
      Under the conditions of this study, it can be said that ultrasonically activated
      irrigation did not reduce the smear layer effectively at 1 min and 0.5 min time
      intervals. According to this result, no difference was observed between the
      penetration of sealers.

PMID- 14973566
TI  - Applying social learning theory to children with dental anxiety.
AB  - Through a review of the literature dental anxiety has been found to be prevalent
      and problematic within the child population. Dentists are forced to treat the
      dentally anxious child in such ways that do little to reduce the anxiety of the
      child and in some cases cause dental anxiety to increase. This article seeks to
      apply Albert Bandura's social learning theory to reduce dental anxiety in
      children, in a preventative nature. A description of the social learning theory
      is offered as well as evidence indicating the effectiveness of applying the
      social learning theory to dental anxiety in children. Finally, suggestions for
      applications within the dental office are discussed.

PMID- 14973567
TI  - Orthodontic treatment of fused and geminated central incisors: a case report.
AB  - A 10-year old Egyptian male presented with a geminated upper right central
      incisor along with a fused and rotated upper left central incisor in cross bite.
      He also had severe crowding in the maxillary arch and a congenitally missing
      lower right first permanent premolar. Orthodontic treatment was carried out to
      align upper right and left central incisors, lateral incisors, and canines.
      Treatment options were discussed.

PMID- 14973568
TI  - AAOMP case challenge: Multiple painful oral ulcers.
AB  - A 66-year old white male was referred with a chief complaint of multiple painful
      oral and pharyngeal ulcerations (Figure 1). He stated his symptoms began four
      months earlier with the occurrence of a mild sore throat, which was followed by
      the development of numerous ulcers throughout the rest of his mouth. Because of
      the pain from these lesions, the patient suffered from dysphagia and resultant
      weight loss.

PMID- 14973569
TI  - Iron oxide chemistry. From molecular clusters to extended solid networks.
AB  - This overview features the chemical background on condensation phenomena of iron
      cations in aqueous solution. The formation of molecular clusters or nanosized
      solid phases is interpreted with illustrative mechanisms building a bridge
      between solution chemistry and solid state chemistry. Iron chemistry gives a very
      nice example of chemical versatility.

PMID- 14973570
TI  - Medicinal chemistry in academia: molecular recognition with biological receptors.
AB  - Why carry out medicinal chemistry at a university, when it means competing with
      the billion-dollar research efforts of the pharmaceutical industry? In academic
      research, the race to get a drug to market is not the prime motivation. Instead,
      university-based medicinal chemistry is driven by the search for new knowledge
      and the opportunity to educate a new generation of chemists. Furthermore,
      academia can complement commercial efforts by addressing diseases neglected by
      private industry.

PMID- 14973571
TI  - A monomolecularly imprinted dendrimer (MID) capable of selective binding with a
      tris(2-aminoethyl)amine guest through multiple functional group interactions.
AB  - A molecularly imprinted dendrimer (MID) with a colorimetric reporter group
      exhibits three-point binding of tris(aminoethyl)amine in THF with a K(assoc)= 3.3
      x 10(6) M(-1).

PMID- 14973572
TI  - Self-assembly of heteroleptic [2 x 2] and [2 x 3] nanogrids.
AB  - Using the HETPHEN concept a general and quantitative approach to the formation of
      heteroleptic nanogrids is illustrated.

PMID- 14973573
TI  - A host-guest complex between a metal-organic cyclotriveratrylene analog and a
      polyoxometalate: [Cu6(4,7-phenanthroline)8(MeCN)4]2PM12O40(M = Mo or W).
AB  - The synthesis and crystal structure of Cu(6)(4,7-phenanthroline)(8)(MeCN)(4)(6+)
      a novel Cu(i)-molecular hexamer is described in which the metal cations and
      phenanthroline molecules self-assemble into a dimer of shallow triangular-shaped
      bowls, within which are located large spherical polyoxometalate anions
      PM(12)O(40)(3-)(M = Mo or W).

PMID- 14973574
TI  - Synthesis and X-ray single crystal structure of a bivalent glycocluster.
AB  - The crystal structure of a bivalent glycocluster containing aromatic amides
      reveals that alkylation of secondary amides alters amide configuration and thus
      carbohydrate presentation. This also facilitates non covalent interactions (azide
      azide, carbonyl-pyranose and aromatic-pyranose) and thus carbohydrate
      carbohydrate stacking.

PMID- 14973575
TI  - A ratiometric fluorescent probe for imaging hydroxyl radicals in living cells.
AB  - A novel fluorescent probe, the detection mechanism of which is based on the 'on
      off' switching of a FRET triggered by the *OH-induced cleavage of a DNA strand,
      has been developed for the ratiometric imaging of *OH.

PMID- 14973576
TI  - The influence of solvation on short strong hydrogen bonds: a density functional
      theory study of the Asp-His interaction in subtilisins.
AB  - The effect of a structural water molecule on the electronic nature of the His64
      Asp32 hydrogen bond in subtilisins is examined by DFT calculations; the
      structural water is found to favor a short strong hydrogen bond in the catalytic
      triad in sharp contrast to some current beliefs.

PMID- 14973577
TI  - Confined organization of Au nanocrystals in glycolipid nanotube hollow cylinders.
AB  - Mild fabrication of anisotropic metal-lipid nanotube (LNT) nanocomposites, in
      which Au nanoparticles of 3-10 nm wide are organized in a glycolipid nanotube
      hollow cylinder, has been achieved by filling the internal channel of the LNT
      with HAuCl(4) aqueous solution by capillary force and subsequent photochemical
      reduction of [AuCl(4)](-).

PMID- 14973578
TI  - Self-indicating amine scavenger resins.
AB  - Self-indicating methylisocyanate resin, which functions as both a scavenger and
      an indicator for amines, was used for in-situ reaction monitoring and
      purification of a urea based library.

PMID- 14973579
TI  - From metal to ligand electroactivity in nickel(II) oxamato complexes.
AB  - The locus of oxidation in square-planar nickel(ii) oxamato complexes can be
      continuously shifted from the metal to the ligand by an appropriate choice of
      electron-donating substituents on the aromatic moiety of the ligand.

PMID- 14973580
TI  - Influence of substrate on self-assembled photonic crystal.
AB  - Freestanding monolayers of two-dimensional particle arrays, in which fine
      particles are two-dimensionally self-assembled in a highly oriented manner, was
      prepared to examine the influence of substrate on the transmission spectra of 2D
      particle array; as a result, the spectrum of the freestanding 2D particle array
      has less noise than that of the 2D particle array on the substrate, and besides,
      agree with the theoretical result particularly in the near-field discussion.

PMID- 14973581
TI  - Highly substituted pyridines via tethered imine-enamine (TIE) methodology.
AB  - A tethered imine-enamine methodology has been developed for the direct conversion
      of 1,2,4-triazines into highly substituted pyridines via the inverse electron
      demand Diels-Alder reaction which avoids the need for a discrete aromatisation
      step. This TIE methodology has also been applied in one pot reaction cascades
      involving 1,2,4-triazines and utilising MnO(2)-mediated tandem oxidation
      processes (TOPs).

PMID- 14973582
TI  - Total synthesis of (+)-belactosin A.
AB  - A concise first total synthesis of the antitumour antibiotic belactosin A is
      reported, involving coupling of beta-lactone carboxylic acid 3 with N-Ala
      aminocyclopropyl alanine 11.

PMID- 14973583
TI  - Cyclopropyl fatty acids implicate a radical but not a cation as an intermediate
      in P450BM3-catalysed hydroxylations.
AB  - Novel cyclopropyl containing fatty acids are good substrates for P450(BM3)
      catalysed hydroxylation and analysis of their oxidation products indicates the
      presence of a radical intermediate (maximum rebound rate 2.6 x 10(10) s(-1)) and
      the absence of any cationic intermediate.

PMID- 14973584
TI  - The Sonogashira coupling reaction catalyzed by ultrafine nickel(0) powder.
AB  - The Sonogashira coupling reaction catalyzed by ultrafine nickel(0) powder has
      been developed; terminal alkynes couple with aryl, alkenyl iodide and aryl
      bromide in the presence of cuprous iodide, triphenylphosphine, potassium
      hydroxide and ultrafine particle nickel(0) to provide the corresponding cross
      coupling products with high yields.

PMID- 14973586
TI  - Controlled functionalization of gold nanoparticles through a solid phase
      synthesis approach.
AB  - A novel solid phase synthetic strategy was developed in this work for controlled
      functionalization of gold nanoparticles.

PMID- 14973585
TI  - Nucleic acid binding properties of thyminyl and adeninyl pyrrolidine-amide
      oligonucleotide mimics (POM).
AB  - Adeninyl POM was prepared using solid-phase peptide chemistry and shown to
      exhibit higher affinity for complementary DNA and RNA than the corresponding
      adeninyl PNA.

PMID- 14973587
TI  - VIII(OH)[O2C-C6H4-CO2].(HO2C-C6H4-CO2H)x(DMF)y(H2O)z(or MIL-68), a new
      vanadocarboxylate with a large pore hybrid topology: reticular synthesis with
      infinite inorganic building blocks?
AB  - V(III)(OH)[O(2)C-C(6)H(4)-CO(2)].(HO(2)C-C(6)H(4)-O(2)H)(x)(DMF)(y)(H(2)O)(z) or
      MIL-68 was solvothermally synthesised in a non-aqueous medium. Its structure,
      built up from octahedral chains connected by terephthalate linkers, exhibits
      large hexagonal channels containing different occluded moieties. Their
      irreversible removal releases a specific surface area of 603(22) m(2).g(-1)(BET).

PMID- 14973588
TI  - Electrospray mass spectrometry of undiluted ionic liquids.
AB  - Ionic liquids have been analyzed in undiluted form using electrospray mass
      spectrometry (ES-MS); results indicate that signal-to-noise ratios for minor
      constituents are comparable to those observed in conventional, diluted ES-MS and
      that this approach could be readily applied for mass spectrometric analysis of
      ionic liquids and ionic impurities/additives dissolved therein, especially those
      that are solvent reactive.

PMID- 14973589
TI  - Surface energy and surface area measurements by 19F MAS NMR of adsorbed
      trifluoroacetic acid.
AB  - Trifluoroacetic acid, when adsorbed on the surface of inorganic materials, is a
      useful (19)F NMR probe molecule for studying surface properties including surface
      energy and surface area.

PMID- 14973590
TI  - Carbon nanotube conducting arrays by consecutive amidation reactions.
AB  - Carbon nanotube conducting arrays were constructed via consecutive amidation
      reactions with the aid of a linker molecule and a condensation agent on a
      patterned amine-terminated glass substrate. The electrical resistivity of the
      nanotube films was sensitive to the degree of coverage for the substrate, making
      it possible to tailor nanotube multilayers suitable for use in micro- or
      nanoscale electronic devices and circuits.

PMID- 14973591
TI  - Preparation of highly accessible mordenite coatings on ceramic monoliths at
      loadings exceeding 50% by weight.
AB  - A mordenite layer with a high accessibility has been synthesised on cordierite
      monolith supports; substantial loadings of mordenite were achieved (above 50 wt%)
      under the synthesis conditions used.

PMID- 14973592
TI  - Preparation of chiral triarylphosphines by Pd-catalysed asymmetric P-C cross
      coupling.
AB  - Enantioselective C-P cross-coupling of diarylphosphines and ortho-substituted
      aryl iodides has been achieved with >90%ee, using an in situ catalyst prepared
      from Et,Et-FerroTANE, Pd(2)(dba)(3) x CHCl(3) and LiBr.

PMID- 14973593
TI  - Nickel-catalyzed highly chemoselective cocyclotrimerization of arynes with
      allenes: a novel method for 10-methylene-9,10-dihydrophenanthrenes.
AB  - The NiBr(2)(dppe)-Zn system effectively catalyzes the [2+2+2]
      cocyclotrimerization of arynes with allenes, leading to 10-methylene-9,10
      dihydrophenanthrenes in moderate to good yields. The cocyclotrimerization is
      highly selective with only the internal double bond of the allenes being involved
      in the reaction.

PMID- 14973594
TI  - Prediction of formation constants of metal-ammonia complexes in aqueous solution
      using density functional theory calculations.
AB  - Density functional theory calculation of gas-phase Delta G of replacement of a
      water molecule by NH(3) on [M(H(2)O)(6)](n+)(g) for 19 different metal ions
      correlates well with Delta G of formation of mono NH(3) complexes of these ions
      in water, suggesting this approach will permit prediction of formation constants
      in aqueous solution, and produce insights into theories of metal complex
      formation reactions.

PMID- 14973595
TI  - Novel imprinted soluble microgels with hydrolytic catalytic activity.
AB  - The synthesis and kinetic characterisation of soluble imprinted acrylamide based
      microgels incorporating arginine and tyrosine derivatives as additional
      functional monomers is reported.

PMID- 14973596
TI  - Cooperative C-F...Si interaction in optically active helical polysilanes.
AB  - Cooperative amplification of the C-F...Si weak interaction between side chains
      and the main chain was found to afford rigid rodlike helical polysilanes with a
      preferential screw sense.

PMID- 14973597
TI  - Easy access to diastereomerically pure platinacycles.
AB  - The synthesis of the first examples of diastereomerically pure platinacycles
      having simultaneously a chiral carbon and a sigma[Pt-C(sp(2), ferrocene)] bond is
      described.

PMID- 14973598
TI  - The kinetics of propene and hexene polymerisation with [(SBI)ZrR]+X-: evidence
      for monomer-dependent early or late transition states.
AB  - Whereas the rates of propene polymerisation catalysed by zirconocene ion pairs
      are strongly anion-dependent, hexene polymerisations are not; the findings
      demonstrate the existence of very different kinetic regimes for two closely
      related reactions.

PMID- 14973599
TI  - First three examples of taxane-derived di-propellanes in Taxus canadensis
      needles.
AB  - The first three examples of taxane-derived [3.3.3][3.4.5] di-propellanes isolated
      from the needles of a yew tree are reported. They differ in their acetylation
      pattern and their biogenesis from a putative taxane precursor is proposed.

PMID- 14973600
TI  - Insights into the reactivity and structure of silylene phosphonium ions.
AB  - Experimental evidence for the intermediate occurrence of a so far unknown
      silylene phosphonium ion is presented and its reactivity and bond situation is
      discussed on the basis of ab initio calculations.

PMID- 14973601
TI  - Fabrication of two-dimensionally ordered macroporous silica materials with
      controllable dimensions.
AB  - The formation of 2-D arrays of cavities of varying size and depth on an electrode
      surface via colloidal templating is described.

PMID- 14973602
TI  - Sn-Beta zeolite as diastereoselective water-resistant heterogeneous Lewis-acid
      catalyst for carbon-carbon bond formation in the intramolecular carbonyl-ene
      reaction.
AB  - The water-tolerant Lewis acid Sn-Beta isomerises citronellal to isopulegol with
      high diastereoselectivity working in batch or in fixed bed reactors with very
      high turnover numbers.

PMID- 14973603
TI  - Porphyrin-acetylene-thiophene polymer wires.
AB  - 5,15-Bis[acetylene-4-(ethylenedioxy)thiophene]-10,20-bis(4
      carboxyphenyl)porphyrin was synthesized by a Sonogashira coupling and polymerized
      to fibres; TEM and AFM images show uniform porphyrin wires with a length of
      several micrometers and a thickness of less than 4 nm.

PMID- 14973604
TI  - Synthesis and characterization of novel chiral sulfonato-salen-manganese(III)
      complex in a zinc-aluminium LDH host.
AB  - A novel heterogeneous catalyst,
      [Zn(2.15)Al(0.86)(OH)(6.02)][Mn](0.19)[C(6)H(5)COO](0.48.2H(2)O, where [[Mn]=
      chiral sulfonato(-)salen-manganese(iii) complex,
      Na(2)MnC(20)H(22)N(2)S(2)O(12)Cl, intercalated into Zn(II)-Al(III) layered double
      hydroxide host], has been synthesized and found to be an effective heterogeneous
      catalyst for the stereoselective epoxidation of R-(+)-limonene using molecular
      oxygen. The catalyst could be recycled without loss of performance.

PMID- 14973605
TI  - Template-free synthesis of single-crystalline cadmium nanotubes.
AB  - By pyrolysis of CdS powder in inert gas, single-crystalline cadmium nanotubes
      growing in the form of a heap, were produced for the first time in high yield.

PMID- 14973606
TI  - Utilisation of [11C]-labelled boron carbonyl complexes in palladium carbonylation
      reaction.
AB  - The use of the [(11)C]BH(3).CO complex as a source of carbon monoxide in the
      carbonylation of iodobenzene catalysed by palladium(0) is described, which allows
      the synthesis of an amide and a lactone in a straightforward manner.

PMID- 14973607
TI  - New magnetically responsive polydicarbazole-magnetite nanoparticles.
AB  - Magnetically responsive COOH-polydicarbazole-magnetite nanocomposites have been
      prepared by chemical oxidation of three COOH-dicarbazole monomers and - in the
      presence of magnetite nanoparticles. These functionalized nanoparticles have been
      tested for DNA hybridization experiments.

PMID- 14973608
TI  - Mesocellular polymer foams with unprecedented uniform large mesopores and high
      surface areas.
AB  - Mesocellular polymer foams with uniform approximately 17 nm cellular pores were
      fabricated using mesocellular silica foams as inorganic templates. The
      mesocellular polymer foams have high surface areas up to approximately 600 m(2)g(
      1) and pore volumes of 1.6 cm(3)g(-1).

PMID- 14973609
TI  - Microwave-assisted Negishi and Kumada cross-coupling reactions of aryl chlorides.
AB  - Rapid Pd or Ni-catalyzed microwave-accelerated Negishi and Kumada cross-coupling
      reactions of aryl chlorides in solution and on solid phase are reported.

PMID- 14973610
TI  - C1 Coupling via bromine activation and tandem catalytic condensation and
      neutralization over CaO/zeolite composites.
AB  - We demonstrate here an alternative scheme for C(1) coupling by way of methane
      bromination, followed by concurrent bromomethane condensation and quantitative
      HBr neutralization; regeneration of the metal oxide with O(2) with recovery of
      Br(2) completes the cycle.

PMID- 14973611
TI  - Spontaneous template-free assembly of ordered macroporous titania.
AB  - Spontaneous formation of ordered macroporous titania is achieved by dropwise
      addition of titanium alkoxides to aqueous ammonia in the absence of auxiliary
      organic templates.

PMID- 14973612
TI  - Synthesis and structural characterisation of a novel phosphine-borane-stabilised
      dicarbanion and an unusual bis(phosphine-borane).
AB  - The reaction between the phosphine-borane-substituted alkene
      [Pr(n)(2)P(BH(3))](Me(3)Si)C[double bond]CH(2) and elemental lithium in THF
      yields the complex [(pmdeta)Li[Pr(n)(2)P(BH(3))](Me(3)Si)CCH(2)](2)(2b) after
      recrystallisation; an X-ray crystallographic study of 2b reveals that the lithium
      is bound to the BH(3) hydrogens of the ligand, with no Li-C(carbanion) contact.

PMID- 14973613
TI  - A versatile pathway for the direct assembly of organo-functional mesostructures
      from sodium silicate.
AB  - Silica mesostructures with well-expressed hexagonal and wormhole framework
      structures and up to 50% organo-functionalization of the framework silicon sites
      have been directly assembled from sodium silicate.

PMID- 14973614
TI  - Protein-DNA interaction: impedance study of MutS binding to a DNA mismatch.
AB  - MutS binding to a double-stranded DNA containing a single nucleotide mismatch can
      be conveniently monitored by impedance spectroscopy and represents the first step
      in developing an electrochemical binding essay for single nucleotide mismatch
      detection.

PMID- 14973615
TI  - Single-step fabrication of drug-encapsulated inorganic microspheres with complex
      form by sonication-induced nanoparticle assembly.
AB  - Sonication of nanoparticle suspensions confined within aqueous droplets of drug
      molecules in toluene produces drug-loaded silica or titania porous microspheres
      with complex morphology and storage/release properties.

PMID- 14973616
TI  - Electrochromic tetrathiafulvalene derivatives functionalised with 2,5-diaryl
      1,3,4-oxadiazole chromophores.
AB  - Electrochromism has been demonstrated by three novel electrochemically-reversible
      compounds and, which were synthesised by Pd catalysed cross-coupling of
      iodotrimethylTTF (6) and 2,6(7)-diiodoTTF (7) with the 2,5-diaryl-1,3,4
      oxadiazole derivatives 1 and 2 containing terminal ethyne and butadiyne groups.

PMID- 14973617
TI  - Reactive barium-promoted Reformatsky-type reaction of alpha-chloroketones with
      aldehydes.
AB  - A Reformatsky-type aldol reaction of alpha-chloroketones with aldehydes has been
      achieved using reactive barium as a low-valent metal in THF; this one-pot process
      is more effective for obtaining the desired beta-hydroxy ketones in high yields
      than the stepwise process in which barium enolates are prepared prior to the
      reaction with aldehydes.

PMID- 14973618
TI  - Direct epoxidation of propylene by molecular oxygen over a catalyst system
      containing palladium and a peroxo-heteropoly compound in methanol.
AB  - A catalyst system consisting of palladium and a peroxo-heteropoly compound in
      methanol showed 81.6% selectivity for propylene oxide at 42.7% propylene
      conversion using molecular oxygen as oxidant in an autoclave reactor at 373 K for
      6 h.

PMID- 14973619
TI  - Formation of cyclic compounds and carbenium ions by conversion of methanol on
      weakly dealuminated zeolite H-ZSM-5 investigated via a novel in situ CF MAS
      NMR/UV-Vis technique.
AB  - In studying the conversion of methanol on weakly dealuminated zeolite H-ZSM-5,
      simultaneously by in situ MAS NMR and in situ UV-Vis spectroscopy under
      continuous-flow conditions, the formation of cyclic compounds and carbenium ions
      were found to be formed already at 413 K.

PMID- 14973620
TI  - A new method of solvent free O- and N-glycosylation using activated carbon fiber
      (ACF) as a promoter. Application to the synthesis of saponin and nucleoside
      analogues.
AB  - By using activated carbon fiber (ACF) as solid acid promoter, we display a new
      system for solvent free O- and N-glycosylation, with a simple process which takes
      place in a drying oven; this method has been applied to the synthesis of sterol
      and triterpene O-glycosides (saponin analogues), as well as nucleoside analogues.

PMID- 14973621
TI  - A powerful route to C-functionalised tetraazamacrocycles.
AB  - The bisaminal template approach represents a powerful synthetic tool for the
      preparation of various C-functionalised tetraazacycloalkanes which are efficient
      precursors of bifunctional chelating agents.

PMID- 14973622
TI  - Modelling catalytic turnover frequencies in ionic liquids: the determination of
      the bimolecular rate constant for solvent displacement from [(C6H6)Cr(CO)2Solv]
      in 1-n-butyl-3-methylimidazolium hexafluorophosphate.
AB  - The bimolecular rate constant for solvent displacement, k(2), from
      [(C(6)H(6))Cr(CO)(2)Solv] by an incoming ligand has been determined in the room
      temperature ionic liquid, [bmim][PF(6)], and is compared to that for the same
      process in cyclohexane and dichloroethane.

PMID- 14973623
TI  - Identification of 5-fluoro-5-deoxy-D-ribose-1-phosphate as an intermediate in
      fluorometabolite biosynthesis in Streptomyces cattleya.
AB  - 5'-Fluoro-5'-deoxy-D-ribose-1-phosphate (FDRP) is identified as a biosynthetic
      intermediate during fluorometabolite biosynthesis in Streptomyces cattleya.

PMID- 14973624
TI  - The first general method for alpha-trifluoromethylation of carboxylic acids using
      BrF3.
AB  - 2-Carbomethoxy-1,1-bis(methylsulfide)-1-alkenes, easily made from carboxylic
      acids, CS(2) and MeI, were treated with BrF(3) producing eventually the desired
      alpha-trifluoromethyl carboxylate derivatives--RCH(CF(3))COOR'--in good yields.

PMID- 14973625
TI  - A practical synthesis of amphiphilic cyclodextrins fully substituted with sugar
      residues on the primary face.
AB  - New amphiphilic cyclodextrins fully substituted with sugar residues on the
      primary face have been synthesised and enzymatically modified.

PMID- 14973626
TI  - A direct meta-lithiation route to 1,3-disubstituted ferrocenes.
AB  - Ferrocenyl sulfides afford meta-lithiation products with up to 94%
      regioselectivity on reaction with s-BuLi; the resulting 1,3-disubstituted
      ferrocenes can then be reacted with a variety of electrophiles.

PMID- 14973627
TI  - The first fullerene-heterofullerene dyad.
AB  - The highly regioselective attack of a C(60) malonate containing a terminal acetyl
      function to the heterofullerene cage C(59)N leads to the formation of the first
      fullerene-heterofullerene dyad, representing a new scaffold for directional
      energy transduction.

PMID- 14973628
TI  - Well-defined self-assembling supramolecular structures in water containing a
      small amount of C60.
AB  - In this communication, we report for the first time on the spherical bilayer
      vesicle formation of a dendritic C(60)-amphiphile-surfactant hybrid in aqueous
      solutions.

PMID- 14973629
TI  - Poly(ethylene glycol) as solvent for transition metal mediated living radical
      polymerisation.
AB  - The use of poly(ethylene glycol)(PEG) with low molecular weights as a novel
      solvent for the transition metal mediated radical polymerisation of methyl
      methacrylate and styrene is reported. The utilisation of PEG leads to
      polymerisation kinetics that differ from those observed with more traditional
      organic solvents. Moreover, the amount of residual copper catalyst in the product
      is greatly reduced by precipitation of the polymer in ethanol.

PMID- 14973630
TI  - Tandem aminoxylation-allylation reactions: a rapid, asymmetric conversion of
      aldehydes to mono-substituted 1,2-diols.
AB  - A facile and rapid synthesis of enantiopure mono-substituted 1,2-diols was
      achieved by the tandem aminoxylation-allylation reactions of aldehydes.

PMID- 14973632
TI  - The affinity of phosphates to zinc(II) complexes can be increased with hydrogen
      bond donors.
AB  - Amino H-bond donors adjacent to a zinc(II) centre increase the affinity of
      phosphates to the zinc(II) centre.

PMID- 14973631
TI  - An efficient approach for aromatic epoxidation using hydrogen peroxide and
      Mn(III) porphyrins.
AB  - Efficient epoxidation, in very high conversions and selectivities, of aromatic
      hydrocarbons with hydrogen peroxide, in the presence of Mn(III) porphyrins
      [Mn(TDCPP)Cl, Mn(beta NO(2)TDCPP)Cl, Mn(TPFPP)Cl] as catalysts is described;
      naphthalene and anthracene afford the anti-1,2:3,4-arene dioxides whereas with
      phenanthrene the 9,10-oxide is obtained.

PMID- 14973633
TI  - Continuous flow homogeneous catalysis using supercritical fluids.
AB  - The continuous flow hydroformylation of 1-octene catalysed by
      Rh/[RMIM][Ph(2)PC(6)H(4)SO(3)](R = 1-propyl, 1-pentyl or 1-octyl) dissolved only
      in the steady state reaction mixture and using scCO(2) as a transport vector for
      both substrates and products gives rates up to 160-240 catalyst turnovers h(-1)
      with low rhodium leaching over a 12 h period at a total pressure of 125-140 bar.

PMID- 14973634
TI  - A novel scandium fluoride, [C2N2H10]0.5[ScF4], with an unprecedented tungsten
      bronze-related layer structure.
AB  - [C(2)N(2)H(10)](0.5)[ScF(4)] exhibits isolated anionic layers of corner-linked
      ScF(6) octahedra enclosing 3-, 4-, 5- and 6-membered rings, with features
      reminiscent of both hexagonal and tetragonal tungsten bronze-type structures.

PMID- 14973635
TI  - Biotinylated and enzyme-immobilized carrier prepared by hetero-bifunctional latex
      beads.
AB  - Biotinylated and pyruvate kinase immobilized nano-bio element have been prepared
      using hetero-bifunctional latex beads, where the enzyme activity is roughly half
      of the free enzyme.

PMID- 14973636
TI  - On the regioselectivity of Pd-catalyzed additions of organoboronic acids to
      unsymmetrical alkynes.
AB  - The Pd-catalyzed reaction of unsymmetrical alkynes with organoboronic acids gave
      a mixture of products and, whose ratios were controlled by the electronic as well
      as steric effects of the substrates.

PMID- 14973637
TI  - Cubane-like structure of a silanethiol--primary amine assembly--a novel, unusual
      hydrogen bond pattern.
AB  - A reaction of silanethiol and primary amine leads to a product whose crystals are
      built of well-defined supermolecules--assemblies of four ammonium silanethiolate
      units (RS(-)H(3)N(+)R')(4) with a novel, unusual 3D hydrogen bond pattern.

PMID- 14973638
TI  - Osteon remodeling dynamics in Macaca mulatta: normal variation with regard to
      age, sex, and skeletal maturity.
AB  - As research into bone maintenance and turnover is accelerated and expanded due to
      public health concerns about osteoporosis and other age-related changes and
      pathologies of bone, nonhuman animal models are becoming increasingly important
      as they allow for enhanced experimental manipulation and environmental control
      relative to humans. Old World Monkeys, such as the rhesus macaque, share
      physiological and developmental characteristics that make these primates
      particularly well suited to such studies. The purpose of this study was to
      characterize normal age and sex variation in osteon remodeling dynamics in
      skeletally immature and mature rhesus macaques. Femoral cross-sections from 75
      Macaca mulatta were examined to evaluate the effect of age, sex, and skeletal
      maturity on osteon remodeling dynamics in this popular research primate. Results
      indicate that sex has a significant effect on osteon area (On.Ar), but generally
      is not an important contributor to normal variation in intracortical remodeling
      dynamics. Age and skeletal maturity, however, contribute significantly to
      variation in osteon population density (OPD), activation frequency (Ac.f), and
      bone formation rate (BFR), as is the case in humans. This study is the first to
      characterize normal age and sex variation in osteon remodeling in growing and
      adult rhesus macaques and its results support the use of this animal as a model
      for age-related changes and pathologies in the human skeleton.

PMID- 14973640
TI  - Chairman's Editorial: Reprioritizing radiologist education: teaching old dogs new
      tricks.

PMID- 14973641
TI  - Editorial: Submitting manuscripts for publication through Manuscript Central.

PMID- 14973643
TI  - Use of infliximab, an anti-tumor necrosis alpha antibody, for inflammatory
      dermatoses.
AB  - BACKGROUND: Infliximab is a monoclonal antibody against tumor necrosis factor
      alpha currently approved by the U.S. FDA for the treatment of Crohn's disease and
      rheumatoid arthritis. Recently, a controlled trial reported its effectiveness for
      psoriasis. OBJECTIVE: The object of our study was to evaluate the efficacy and
      safety of infliximab for inflammatory or autoimmune cutaneous disorders. METHODS:
      A retrospective chart review was performed for patients who received infliximab
      at the University of Miami, Cedars Medical Center. RESULTS: Patients with various
      disease, including panniculitis, pityriasis rubra pilaris, eosinophilic
      fasciitis, discoid lupus erythematosus, and necrobiosis lipoidica diabeticorum,
      received infliximab infusion at a dose of 5 mg/kg. All patients had refractory
      disease or adverse effects to previous therapy, which included cyclosporine,
      systemic steroids, azathioprin, clofazimine, mycophenolate mofetil, acitretin,
      UVB, and thalidomide. Six out of the seven patients improved after treatment.
      CONCLUSIONS: Infliximab was well tolerated in most patients and the majority
      benefited from the use of infliximab.

PMID- 14973644
TI  - Generalized cutis laxa associated with heavy chain deposition disease.
AB  - BACKGROUND: Cutis laxa is a heterogeneous group of inherited and acquired
      disorders characterized clinically by loose skin and histologically by altered
      elastic tissue. Heavy chain deposition disease is a very rare monoclonal
      immunoglobulin disorder, distinct from multiple myeloma, in which there is
      production and deposition of defective immunoglobulin heavy chains without light
      chain deposition. OBJECTIVE: We describe a case of acquired cutis laxa associated
      with heavy chain deposition disease. RESULTS: A 50-year-old male presented with
      acute renal failure, IgG4 heavy chain deposition in the kidneys, and no evidence
      of multiple myeloma. Four years later, he developed generalized acquired cutis
      laxa, emphysema, and a peripheral polyneuropathy. On pathology, there was
      destruction of elastic fibers within the dermis. CONCLUSION: This case describes
      a previously unreported association between acquired cutis laxa and heavy chain
      deposition disease.

PMID- 14973645
TI  - Basaloid follicular hamartoma with trichoblastomatous proliferations.
AB  - BACKGROUND: Basaloid follicular hamartomas (BFH) are rare, benign, adnexal
      lesions with diverse clinical presentations. Previous studies documented BFHs
      with fibroepithelioma of Pinkus-like proliferations, or proliferations that
      resemble trichoepitheliomas. OBJECTIVE: We report on a patient with linear,
      unilateral BFH and extensive trichoblastomatous proliferations involving the
      right arm, torso, and leg. An 18-year-old female presented with multiple,
      hyperkeratotic, linear nodules and plaques limited to her right side from the
      shoulder to the leg. The lesions had existed since birth and gradually increased
      over time. RESULTS: The lesions contained hyperpigmented, exophytic nodules with
      acanthosis, pseudoepitheliomatous hyperplasia, focally associated with
      hyperkeratosis, and squamous eddies. Some areas contained trichoepithelioma-like
      proliferations, or large nodules of basaloid cells with numerous cystic spaces,
      marked hyperpigmentation, and melanophages. The diagnosis was linear, unilateral
      BFH with an unusual trichoblastomatous component. CONCLUSION: While
      trichoblastomatous proliferations could occur in a BFH, to our knowledge this
      finding has not been reported.

PMID- 14973646
TI  - Presentation of telangiectasia macularis eruptiva perstans as a long-standing
      solitary plaque associated with renal carcinoma.
AB  - BACKGROUND: Mastocytosis is a rare disease characterized by a primary
      pathological increase in mast cells in different tissues. The skin is the most
      frequently affected organ. Cutaneous mastocytosis, including urticaria
      pigmentosa, solitary mastocytoma, diffuse cutaneous mastocytosis, and
      telangiectasia macularis eruptiva perstans (TMEP), is usually distinguished from
      systemic mastocytosis. TMEP is characterized mainly by telangiectatic macules.
      OBJECTIVE AND METHODS: We report a case of TMEP with an unusual clinical
      presentation as a solitary plaque of telangiectatic macules. A renal clear cell
      carcinoma was detected in a workup for systemic mastocytosis. We discuss the
      clinical and histological findings and treatment of TMEP. CONCLUSIONS: TMEP is a
      rare form of mastocytosis, which occurs mainly in adults, generally has a good
      prognosis, and little tendency to urticate or show constitutional symptoms.
      Clinicians should consider this disorder when confronted with a progressive
      atypical telangiectatic lesion. However, the malignant neoplasm also found in
      this patient is of uncertain significance.

PMID- 14973660
TI  - Guidelines for institutions granting bariatric privileges utilizing laparoscopic
      techniques.

PMID- 14973662
TI  - Scientific inquiry: why don't surgeons practice what they preach?

PMID- 14973667
TI  - The future is now Surgical Endoscopy announces the electronic publication of
      multimedia articles and dynamic manuscripts.

PMID- 14973675
TI  - Intrahepatic subcapsular hematoma complicating laparoscopic cholecystectomy.
AB  - A 64-year-old woman underwent endoscopic retrograde cholangiopancreatography for
      bile duct stones, followed 2 days later by an uneventful laparoscopic
      cholecystectomy. She presented after 10 days with upper abdominal discomfort,
      nausea, and pyrexia. Investigations revealed a decrease in hemoglobin, and
      computed tomography identified a large intrahepatic subcapsular hematoma in
      segments V and VI. There was no intraabdominal collection and the rest of the
      viscera were normal. The collection was drained percutaneously under ultrasound
      guidance and a wide-bore catheter placed. She was treated with intravenous
      antibiotics and the catheter was removed 14 days later upon cessation of
      drainage. Serial ultrasonographic examinations showed a reduction in the size of
      the hematoma and complete resolution at 4 months. She remained well and
      asymptomatic at follow-up 16 months later. We report this case due to its rarity
      and review the previously documented cases of this complication.

PMID- 14973676
TI  - Endoscopic repair of gastrostomy after inadvertent removal of percutaneous
      endoscopic gastrostomy tube.
AB  - Percutaneous endoscopic gastrostomy (PEG) tube placement has become the preferred
      method of enteral feeding for many patients. Neurologic disease and cancer are
      the most frequent indications for PEG tube placement. PEG tubes are also becoming
      more frequent in trauma patients for early initiation of enteral feeding.
      Inadvertent PEG tube removal is a well-known complication of PEG tubes. Patients
      undergoing PEG tube placement are frequently malnourished and in poor general
      medical condition, making them relatively high risk for surgical intervention. In
      the past, after early inadvertent PEG removal, patients underwent laparotomy for
      surgical repair of the gastrostomy site. Recently, laparoscopic replacement of
      the PEG tube has been described. We present a new technique of endoscopic repair
      of the gastrostomy site with hemoclip placement followed by later PEG tube
      placement.

PMID- 14973683
TI  - Robot-assisted mediastinal parathyroidectomy.
AB  - We report the first case of robot-assisted thoracoscopic resection of a
      mediastinal parathyroid adenoma in the aorto-pulmonary window. Intervention
      planning was based on preoperative CT-MIBI image fusion, a new imaging modality
      that enabled reliable and precise localization of the parathyroid. The technique
      consists of taking MIBI-SPECT and CT separately, using a fixation unit that
      provides reproducible positioning of the patients head and neck. The data sets
      are then superimposed upon each other using special software. After the
      localization process, a minimally invasive operation was performed using the
      DaVinci operating robot. The procedure proved not only to be feasible but also
      safe and not time-consuming. The postoperative course was uneventful, and the
      patient was discharged 4 days postoperatively. Compared to conventional
      thoracoscopic surgery, the robotic operating system provides better visualization
      of the operating field and facilitates the movement of the instruments. Precise
      preoperative imaging enables the careful planning of robot-assisted surgery for
      ectopic parathyroids located at relatively inaccessible regions such as the
      anterior mediastinum.

PMID- 14973690
TI  - Laparoscopic management of Chilaiditi's syndrome.
AB  - Chilaiditi's syndrome refers to the symptoms of abdominal pain, distention,
      vomiting, anorexia, and constipation caused by hepatodiaphragmatic interposition
      of the intestine. Although patients with this radiographic finding are commonly
      asymptomatic, presentation with symptoms is rare and accurately refers to this
      syndrome. There is an increased incidence of Chilaiditi's syndrome among mentally
      ill adults. Traditionally, Chilaiditi's syndrome is managed medically by
      discontinuing causative medicines. However, among the mentally ill population
      whose psychotropic medications precipitate the interposition of the colon,
      ceasing these psychotropic medications is not an appropriate option. The case
      presented involves a mentally ill patient with Chilaiditi's syndrome who was
      successfully managed with laparoscopic colopexy. At follow-up, the patient
      reported marked improvement of abdominal symptoms.

PMID- 14973691
TI  - Perforation of an ileostomy by a retained percutaneous endoscopic gastrostomy
      (PEG) tube bumper.
AB  - Percutaneous endoscopic gastrostomy (PEG) has become the procedure of choice for
      long-term enteral feeding. Complications are generally infrequent and often
      avoidable. We describe an unusual case in which a PEG tube bumper caused
      subcutaneous perforation of an ileostomy. After conservative treatment proved
      unsuccessful, revision of the ileostomy via a peristomal incision was performed,
      with good result. Caution must be exercised before considering the severance of a
      PEG tube at the skin, especially in patients with an ileostomy.

PMID- 14973692
TI  - Should surgeons be told what research they can do?

PMID- 14973693
TI  - A prospective randomized study of prophylactic antibiotics in elective
      laparoscopic cholecystectomy.

PMID- 14973724
TI  - Multimedia article. Laparoscopic infracolic necrosectomy for infected pancreatic
      necrosis.
AB  - Infected pancreatic necrosis carries a high morbidity and mortality from sepsis
      and multisystem organ failure. Following confirmation of the infection by CT
      guided fine needle aspiration, treatment consists of broad spectrum antibiotics
      (imipenim-cilastin) followed by emergency open (laparotomy) digital necrosectomy
      and insertion of drains for postoperative lavage with hyperosmolar dialysate as
      advocated by Beger et al. This video shows an alternative laparoscopic technique
      to open necrosectomy and has been used in Dundee since 1994. After elevation of
      the transverse colon, the lesser sac is opened through the root of the transverse
      colon between the middle and left colic vessels. The necrosectomy is accomplished
      from inside the lesser sac under vision with a combination of pulsed irrigation
      and graspers. On completion of the necrosectomy, two large drains are inserted
      into the lesser sac for postoperative irrigation. The experience with this
      technique has been favorable with a patient survival of 85%.

PMID- 14973726
TI  - Thoracoscopic plication of the diaphragm for postoperative phrenic paralysis: a
      report of two cases.
AB  - Unilateral phrenic nerve paralysis after cardiothoracic surgery is not uncommon.
      When symptomatic, it can require surgical treatment. Plication of the diaphragm
      through a thoracotomy is known to provide excellent long-term results. Plication
      is now being performed via video-assisted thoracoscopic surgery (VATS). We report
      the cases of two patients with postoperative left phrenic nerve paralysis who
      underwent plication of the diaphragm using VATS and achieved total relief of all
      symptoms.

PMID- 14973727
TI  - Needle-knife suprapapillary sphincterotomy avoids postprocedure pancreatitis in
      patients with sphincter of Oddi dysfunction of biliary type II: a report of three
      cases.
AB  - We report the cases of three patients who fulfilled the criteria for sphincter of
      Oddi dysfunction of biliary type II and underwent needle-knife suprapapillary
      sphincterotomy. These patients presented with episodes of biliary-type pain after
      cholecystectomy and significant elevation of liver enzymes. Ultrasonography and
      MRI cholangiography revealed dilatation of the common bile duct, without visible
      stones. The patients all underwent needle-knife suprapapillary sphincterotomy
      because free cannulation of the common bile duct could not be achieved. Needle
      knife suprapapillary sphincterotomy enabled catheterization of the common bile
      duct. After clearing of the common bile duct with a balloon catheter, no stones,
      fragments of stones, or sludge were observed to exit from the sphincterotomy.
      None of our patients developed postprocedure pancreatitis. When needle-knife
      suprapillary sphincterotomy is performed by an experienced biliary endoscopist,
      it is a safe and effective procedure for patients with sphincter of Oddi
      dysfunction of biliary type II, who otherwise constitute a high-risk group for
      the development of postsphincterotomy pancreatitis.

PMID- 14973734
TI  - Primary endotracheal neurogenic tumors.
AB  - Benign tumors in the tracheobronchial tree are rare. We report two cases of
      primary endotracheal neurogenic tumors in patients who presented insidiously.
      Both patients did not manifest other clinical features of neurofibromatosis (Von
      Recklinghausen's disease). A single procedure using rigid bronchoscopy and
      neodymium: yttrium-aluminum-garnet laser resection resulted in excellent
      resolution of airway patency with good follow-up results in both cases.

PMID- 14973743
TI  - Laparoscopic pancreatic cystgastrostomy via the lesser sac approach.
AB  - Laparoscopic cystgastrostomy offers the benefits of a minimally invasive
      procedure while providing effective drainage for pancreatic pseudocysts. The
      lesser sac approach to laparoscopic cystgastrostomy provides adequate working
      space with excellent visualization. This assures meticulous hemostasis,
      debridement of the cyst, and wide internal drainage of the pancreatic pseudocyst.
      Additionally, the laparoscopic approach to this difficult problem can be
      augmented by other minimally invasive therapies. This video outlines the
      management of a patient with a pancreatic pseudocyst and concomitant splenic vein
      thrombosis treated with preoperative splenic embolization and laparoscopic
      cystgastrostomy via the lesser sac approach.

PMID- 14973744
TI  - Peritoneal tear leads to leakage of carbon dioxide into the peritoneal cavity.

PMID- 14973745
TI  - Prosthetic material for crural closure in laparoscopic antireflux surgery.

PMID- 14973749
TI  - Mini-laparoscopic placement of a peritoneal dialysis catheter.
AB  - BACKGROUND: The laparoscopic placement of continuous ambulatory peritoneal
      dialysis (CAPD) catheters is now an accepted technique. We evaluated a new
      technique for CAPD catheter placement that requires only a single 2-mm port.
      METHODS: A pilot study was conducted at an academic minimally invasive surgery
      center. Seven consecutive patients in whom a CAPD catheter was required underwent
      placement of a 2-mm Veress port and a laparoscope. A carbon dioxide
      pneumoperitoneum was induced up to 14 mmHg. Under direct visualization with a 2
      mm scope, a CAPD catheter was advanced over the right lower quadrant toward the
      pelvis using a modified Seldinger technique. RESULTS: Seven patients (four women
      and three men) with end-stage renal disease underwent mini-laparoscopic placement
      of a CAPD catheter. Mean patient age was 35.3 +/- 11.3 years (range, 17-50). Mean
      operative time was 20.7 +/- 5.0 min (range, 14-29). Patients were dialyzed in the
      immediate postoperative period. No leaks were identified, and there were no
      intraoperative or postoperative complications. CONCLUSION: A mini-laparoscopic
      technique using a single 2-mm port and a modified Seldinger technique is
      feasible, safe, and effective for peritoneal dialysis catheter placements.

PMID- 14973750
TI  - Concomitant laparoscopic gastric and biliary bypass and bilateral thoracoscopic
      splanchnotomy: the full package of minimally invasive palliation for pancreatic
      cancer.
AB  - INTRODUCTION: Pancreatic cancer is unresectable in 80% or more of patients.
      Biliary and duodenal obstruction and intractable abdominal and back pain are the
      most common complications of the disease. These complications may be palliated
      effectively using minimally invasive techniques. Their combined application in a
      single setting is presented and discussed in this article. CASE REPORT: A 59-year
      old man with a locally advanced carcinoma of the head of the pancreas presented
      with obstructive jaundice and intractable pain requiring opiate analgesia. An
      attempt at endoscopic biliary stenting was unsuccessful, and a percutaneous
      biopsy was deemed unsafe. Preoperative magnetic resonance cholangiography showed
      cystic duct insertion abutting the upper limit of the biliary stricture. A
      laparoscopic Roux-en-Y hepaticojejunostomy, prophylactic loop gastroenterostomy,
      and tumor biopsy were combined with a bilateral thoracoscopic splanchnotomy.
      RESULT: Surgery and subsequent recovery were uneventful, and the patient was
      discharged from hospital on the fourth postoperative day off opiates. He remained
      free of jaundice and severe pain, until 6 months later, when he represented with
      jaundice, cachexia, and proximal small bowel obstruction secondary to multiple
      liver and peritoneal metastases. He underwent further palliative laparoscopic
      enteric bypass with resolution of the intestinal obstruction, but died of the
      disease 10 days later. CONCLUSION: Laparoscopic gastric and biliary bypass and
      bilateral thoracoscopic splanchnotomy may be safely combined to provide an
      effective comprehensive minimally invasive palliation of incurable pancreatic
      cancer.

PMID- 14973751
TI  - Mediastinal bronchogenic cyst treated by mediastinoscopic drainage.
AB  - Bronchogenic cysts are rare congenital anomalies located in the mediastinum and
      lung parenchyma. We present the clinical findings and describe the
      mediastinoscopic treatment of a bronchogenic cyst at the subcarinal space in a 50
      year-old man. CT revealed a lesion at the subcarinal space with soft tissue
      density. Initially, mediastinoscopy was performed for diagnostic purposes.
      Histopathological evaluation of biopsy material taken from the cyst wall
      confirmed that the lesion was a bronchogenic cyst. The cyst contents were drained
      and a sclerosant agent was applied to the cyst lumen via the drainage tube.
      Mediastinoscopy not only provides diagnostic information but can also be used
      safely in the treatment of anterior bronchogenic cysts in patients not amenable
      to a second operation.

PMID- 14973752
TI  - Venocutaneous fistula.
AB  - This is the first description of venocutaneous fistula, a late complication of
      elective laparoscopic cholecystectomy that arose 18 months after the initial
      operation. Postoperatively, the patient twice developed an abscess in the
      abdominal wall at the former site of the umbilical trocar. The first abscess
      occurred on the 6th postoperative day; the second, after 14 months. After an
      additional 4 months, a fistula opening appeared just below the umbilicus.
      Fistulography revealed a connection with the venous system of the omentum majus.
      During subsequent resection of the fistula, a pigment gallstone was retrieved
      from the base of the fistula.

PMID- 14973753
TI  - Videothoracoscopic resection of intrathoracic neurogenic tumors: report of two
      cases.
AB  - Two cases of intrathoracic neurogenic tumors are discussed. The benign neoplasms
      were located in the posterior mediastinum and caused no clinical symptoms. In
      both cases, complete resection of the lesion was achieved by video-assisted
      thoracic surgery (VATS). There were no intraoperative complications.
      Postoperatively, one patient presented with Claude Bernard-Horner syndrome, which
      resolved spontaneously after 1 week. Although the great majority of mediastinal
      neurogenic neoplasms are benign, resection is necessary to prevent malignant
      transformation and intraspinal extension.

PMID- 14973754
TI  - Laparoscopic resection of an abdominal wall desmoid using a modified suture
      traction technique: the "marionette trick".
AB  - Desmoids are rare mesenchimal tumors that may originate also inside the abdomen
      or in the abdominal wall. These tumors are biologically characterized by a
      tendency to local growth, and only rarely are they able to develop distant
      metastases. Surgical excision usually is the best treatment with a chance of a
      cure. In the few reports on intraabdominal or abdominal wall desmoids, open
      surgery always was performed. The first case of successful laparoscopic resection
      of a symptomatic anterior wall desmoid tumor with intraabdominal growth is
      reported. During the procedure, it was difficult to mobilize and grasp the mass
      using the common laparoscopic instruments, but with the help of the "marionette
      trick," modified suture traction technique, the tumor could be removed easily
      using only three trocars. With four traction sutures minimizing the wall trauma,
      the trick made it possible to mobilize the mass in at least, seven directions,
      according to the principles of physical forces and vectors. This simple trick can
      be helpful for other common laparoscopic procedures, avoiding the insertion of
      sometimes ineffective instruments through more traumatic trocars.

PMID- 14973755
TI  - Fatal bile pulmonary embolism after radiofrequency treatment of a hepatocellular
      carcinoma.
AB  - Radiofrequency is increasingly used to manage liver tumors. This report describes
      the case of a 74-year-old man who received two courses of percutaneous
      radiofrequency thermal ablation for a hepatocellular carcinoma over a 4-month
      period. He subsequently required computed tomography-guided drainage for an area
      of intrahepatic necrosis. During the procedure, hemobilia developed, followed by
      respiratory distress and collapse. The diagnosis of bile pulmonary embolism was
      established on the basis of high biliary acid concentrations in pulmonary fluid
      aspiration and blood plasma. Radiofrequency thermoablation provides local control
      of advanced liver tumors with low recurrence and morbidity. However, this
      interventional procedure risks damage to liver parenchyma involving vascular and
      biliary structures, which may lead to biliary-venous fistula and possible bile
      emboli.

PMID- 14973756
TI  - Small bowel perforation after incomplete removal of percutaneous endoscopic
      gastrostomy catheter.
AB  - Percutaneous endoscopic gastrostomy (PEG) is a well-established technique for
      providing long-term nutritional support. The advantages and most frequent
      complications have been widely documented, but less is known about the danger of
      removing or replacing a PEG by cutting the device at skin level without
      endoscopic assistance to ensure the removal of the inner part. Laparotomy is
      often required in elderly and high-risk patients to relieve an intestinal
      obstruction or perforation. We describe a fatal case of small bowel perforation,
      resulting from the inability to remove an inner bumper.

PMID- 14973758
TI  - Amniotic fluid exchange vs amniofusion in gastroschisis.

PMID- 14973757
TI  - Choledocholithiasis caused by migration of a surgical clip into the biliary tract
      following laparoscopic cholecystectomy.
AB  - As experience with laparoscopic cholecystectomy (LC) has increased, so have the
      number and variety of complications. We report a case of choledocholithiasis
      caused by migration of a surgical clip applied during LC. A 57-year-old Japanese
      man who had undergone LC 6 years previously was referred to our hospital with
      pruritus and jaundice. Magnetic resonance cholangiopancreatography and
      ultrasonography revealed a solid mass in the common hepatic duct and dilatation
      of the intrahepatic bile ducts. Abdominal arteriography demonstrated interruption
      of the right hepatic artery by surgical clips. Five days after a biopsy of the
      mass was performed through a percutaneous transhepatic biliary drainage tube, the
      mass moved to the terminus of the common bile duct along with one of the surgical
      clips. A basket catheter was used to remove the mass via endoscopy. Despite the
      fact that other clips in the common hepatic duct were partially exposed, the
      patient has been well for 2 years with no additional interventions.

PMID- 14973760
TI  - Prediction of postoperative gas bloating after laparoscopic antireflux procedures
      based on 24-h pH acid reflux pattern.

PMID- 14973761
TI  - Laparoscopic management of mesenteric cysts.

PMID- 14973762
TI  - Guidelines for institutions granting bariatric privileges utilizing laparoscopic
      techniques. Society of American Gastrointestinal Endoscopic Surgeons (SAGES) and
      the SAGES Bariatric Task Force.

PMID- 14973764
TI  - Indexes to Volume 22, 2003.

PMID- 14973765
TI  - Technical performance: relation between surgical dexterity and technical
      knowledge.
AB  - Technical performance consists of surgical knowledge, judgment, and dexterity.
      Although assessment of surgical dexterity is now possible, assessing technical
      knowledge and its relation to dexterity has not been elucidated. Surgeons of
      varying experience were recruited to the skills laboratory to undertake three
      assessments: simple surgical dexterity (at 14 stations scored by motion
      analysis), an operating room equipment examination, and a novel error analysis.
      The scores were correlated, and p < 0.05 was deemed to be significant. Thirty
      surgeons were recruited; and construct validity was exhibited in all areas.
      Correlations were shown to exist between the two knowledge examinations
      (Spearman's rho = 0.39). Correlations existed between all dexterity task
      parameters and the equipment examination, whereas they existed for only 15 of the
      28 parameters of the error examination and were always weaker. The stronger
      correlations between dexterity and instrument and operating room (OR) equipment
      reflect greater surgical experience and time spent in the OR. The weaker
      correlations between the error analysis and dexterity suggest that these skills
      are learned at different times. The identification of common surgical errors
      should be more formally taught to ensure greater uniformity.

PMID- 14973766
TI  - Quantitative evaluation of the utero-ovarian venous pattern in the adult human
      female cadaver with plastination.
AB  - We described the anatomy of the utero-ovarian venous system in the adult
      postmenopausal female cadaver using casts and the von Hagen's plastination
      technique. To qualitatively and quantitatively evaluate the uterine vein, the
      utero-ovarian arcade, the ovarian vein and the ramus communicans between left and
      right parametrium, we injected epoxy resin into the internal iliac vein and
      artery and the ovarian vein and artery in six cadavers. In two cases the internal
      genital organs were excised before injection and in the other four after the
      injection and polymerization of the resin. All specimens were macroscopically
      examined and venous diameters were digitally measured, the average values of the
      measured diameters being 3.38 mm for the uterine vein, 3.71 mm for the utero
      ovarian arcade, 3.49 mm for the ovarian vein, and 3.71 mm for the ramus
      communicans. The veins were completely filled out and could be best examined in
      the four cases where in situ injection was performed. We could observe that the
      utero-ovarian arcade is an important vein with a caliber similar to that of the
      ovarian and uterine veins, that there is an impressive network of venous
      anastomoses between the left and right parametrium and that the fallopian tubes
      are drained by three separate veins: internal, median, and external tubal veins.
      Pelvic venous congestion was present in two specimens; in one of them it was
      located in the region of the left uterine vein and in the other one in the region
      of the left ovarian vein. Given the similar average diameters of the uterine
      vein, ovarian vein, and utero-ovarian arcade, we assume that there is no
      preferential uterine or ovarian venous drainage and that the veins of the
      internal genital organs are behaving like a venous pool. Nevertheless, congestion
      can affect limited sites, which can and should be treated locally.

PMID- 14973768
TI  - Primary reconstruction of a degloved hand using multiple toe transfers on a
      single pedicle and a reversed radial artery flap.
AB  - This case study reports one-stage reconstructive surgery on an 18-year-old man
      who was injured by an industrial roller machine and who presented with a degloved
      hand. Non-replantable delgloving occurred in all fingers, with the loss of the
      palmar and part of the dorsal skin. Multiple free contiguous toes were
      transferred based on a single dorsalis pedis artery pedicle. The artery was
      anastomosed to a reversed radial artery flap, which was used to cover the palm
      for primary reconstruction of the degloved hand. Multiple toes were harvested
      from the same foot, based on a single pedicle, to contain the potential morbidity
      to one foot, to enable primary reconstruction, and to decrease the length of the
      operation. The flaps healed well, and the patient demonstrated adequate tripod
      pinch and key pinch with the transferred toes, with a two-point discrimination of
      12 mm at 1-year follow-up. The patient was satisfied with both the appearance and
      function of the hand and foot.

PMID- 14973769
TI  - Distal anterior interosseous nerve in the recurrent motor branch graft for
      reconstruction of a median nerve neuroma-in-continuity.
AB  - Median nerves with neuromas-in-continuity are preferably managed by the
      identification and preservation of the functioning motor fascicles proximal and
      distal to the neuroma. The non-functioning, painful sensory fibers are divided
      proximally and distally and are reconstructed with nerve grafts. In cases where
      the proximal motor fascicle may not be safely and effectively isolated because of
      scarring or previous surgical intervention, the distal anterior interosseous
      nerve (dAIN) may be grafted to the recurrent motor branch of the median (RMB)
      nerve distal to the neuroma. The primarily motor fibers of the dAIN provide an
      expendable donor of adequate size and fascicle number to restore thenar muscle
      function.

PMID- 14973770
TI  - Vascularized fibular grafting in the treatment of methicillin-resistant
      Staphylococcus aureus osteomyelitis and infected nonunion.
AB  - Twenty patients with methicillin-resistant Staphylococcus aureus (MRSA)
      osteomyelitis and bone infection were treated with vascularized fibular grafts.
      There were 16 males and four females, and the patient ages at operation ranged
      from 17 to 73 years. Nine of the lesions affected the femur, eight the tibia, and
      there were three others. All of the patients were treated with extensive
      debridement of the lesions and local antibiotic therapy. Continuous local
      irrigation was applied in two patients, antibiotic-formulated bone cement in
      five, and both in 10 patients. Recurrence of local infection occurred in six
      patients, including one failed graft. Eventually, 18 of the 20 cases attained
      successful subsidence of the inflammation. The mean period required to obtain
      radiographic bone union was 7 months in the femoral reconstruction group, 6.1
      months in the tibial reconstruction group, and 6 months in the remaining
      patients. The authors believe that vascularized fibular grafting is the most
      reliable procedure for the treatment of MRSA osteomyelitis and infected nonunion.

PMID- 14973771
TI  - Obturator nerve injury associated with femur fracture fixation detected during
      gracilis muscle harvesting for functioning free muscle transfer.
AB  - A rare case is reported in which injury of the motor nerve of the gracilis
      (obturator nerve) was detected during its harvesting for functioning free muscle
      transfer. The probable cause of this rare injury was considered to be accidental
      penetration while drilling for a proximal locking screw in intramedullary nailing
      during previous femur fracture surgery.

PMID- 14973772
TI  - Masseteric-facial nerve anastomosis: case report.
AB  - When a viable proximal facial nerve is not accessible, facial nerve paralysis has
      been managed with hypoglossal facial anastomosis, which results in varying
      degrees of hemiglossal atrophy and its sequelae. These authors have used the
      masseteric nerve to neurotize the facial nerve in one patient.

PMID- 14973773
TI  - Free flap neovascularization: myth or reality?
AB  - The blood supply of 17 free flaps was studied several months after surgery. The
      aim was to see whether or not the free flaps acquired blood flow through vessels
      across the flap inset independently of the main vascular anastomoses. A color
      Doppler flowmeter was used to identify the original arterial and venous
      anastomoses, the vessels in the margin of the flap, and also across the flap
      inset. The main vascular pedicle was then manually compressed for 2 min and blood
      flow was again examined in the vessels at the margin of the flap. The flap
      vessels (post-anastomotic), the anastomoses, and the recipient vessels (pre
      anastomotic) could be identified in every case. There was no evidence of
      anastomotic stenosis. No vessels (neo-vascularization) greater than 0.5 mm could
      be identified across the flap inset. Small arteries could be identified in the
      flap near the inset. These vessels emptied completely on manual compression of
      the vascular pedicle for 2 min and did not refill until the compression was
      released. This evidence suggests that the free flaps do not receive significant
      blood flow through vessels across the flap inset, and are therefore significantly
      dependent for vascularity on the original anastomoses even 1 year after surgery.

PMID- 14973774
TI  - Continuous and real-time blood perfusion monitoring in prefabricated flaps.
AB  - The Thermal Diffusion Probe (TDP) System allows continuous real-time measurement
      of tissue perfusion in flaps. The authors used a TDP with two thermistors, one
      active, the other passive, embedded in a 0.9-mm diameter catheter to measure
      continuous tissue perfusion in rabbit epigastric flaps. The distal thermistor is
      heated to 2 degrees C above the tissue baseline temperature. The power required
      to maintain this temperature difference is mathematically related to the tissue
      perfusion in the volume surrounding the probe tip. Central and peripheral TDPs
      were placed. The TDP effectiveness in detecting and measuring daily tissue
      perfusion in buried epigastric flaps was tested. Contralateral epigastric
      pedicles were transposed into the flaps prior to ligation of the original
      pedicle. Flaps with transposed pedicles showed a progressive and significant
      increase in tissue perfusion during the initial 3 weeks of the experiment,
      compared to flaps without the pedicle transfer. The TDP System is a useful
      experimental method for the continuous and real-time quantification of flap
      perfusion and may be helpful in making clinical decisions about prefabricated
      flap transfer.

PMID- 14973775
TI  - Immune unresponsiveness by intraportal UV-B-irradiated donor antigen
      administration requires persistence of donor antigen in a nerve allograft model.
AB  - The purpose of this study was to characterize the mechanism of unresponsiveness
      produced by the intraportal administration of ultraviolet-B (UV-B)-irradiated
      donor antigen. Pretreated Buffalo rats accepted Lewis nerve allografts, had
      decreased in vitro T-cell reactivity, and demonstrated nerve regeneration and
      recovery of limb function, while rejecting third-party nerve allografts.
      Regenerated nerve grafts were then retransplanted into a second naive recipient.
      Rejection of the retransplanted allograft by naive donor-strain, but not
      recipient-strain, animals suggests that the allografts were completely replaced
      by host tissue. Pretreated Buffalo rats were also given a second Lewis allograft
      after the first had regenerated. The second allograft was rejected and in vitro
      immune reactivity was comparable to naive animals. Because the unresponsiveness
      state was extinguished with loss of exposure to donor antigen, these findings
      suggest that the intraportal administration of UV-B-irradiated donor antigen
      works by anergic or suppressive regulatory, rather than deletional, mechanisms.

PMID- 14973776
TI  - Effects of vascular endothelial growth factor on nerve regeneration in acellular
      nerve grafts.
AB  - The purpose of this study was to evaluate the effects of human recombinant
      vascular endothelial growth factor (VEGF-165) on peripheral nerve axonal
      sprouting and elongation following peripheral nerve injury and repair. Two
      centimeter nerve gaps were created in rat peroneal nerves and repaired with
      either peripheral nerve autografts, acellular peripheral nerve isografts, or VEGF
      165-treated acellular peripheral nerve isografts. Four months postoperatively,
      the peroneal nerves were harvested and histomorphometric analysis was performed.
      The reinnervated extensor digitorum longus (EDL) muscles were harvested and
      weighed. At the proximal nerve gap coaptation site, there was a statistically
      significant increase in the total number of axons and percent neural tissue in
      the VEGF-treated acellular nerve graft group, compared with the acellular
      peripheral nerve isograft and autograft groups. At the distal coaptation site,
      however, the total number of axons and percent neural tissue was similar in the
      acellular and VEGF-treated groups, which was significantly less than the
      autograft group. VEGF-165 treatment of acellular nerve grafts resulted in greater
      EDL muscle masses than acellular nerve grafts alone. VEGF treatment of acellular
      peripheral nerve isografts enhances axonal sprouting, resulting in an increased
      number of axons and percent neural tissue at the proximal nerve graft coaptation
      site. In the absence of any cellular elements, VEGF-impregnated acellular
      peripheral nerve grafts do not demonstrate enhanced axonal elongation, as noted
      by relatively few axons at the distal nerve graft coaptation site.

PMID- 14973777
TI  - On "Management of significant venous discrepancy with microvascular venous
      coupler" (J Reconstr Microsurgery 2003;19:377-380).

PMID- 14973778
TI  - Deficiency of GDP-Man:GlcNAc2-PP-dolichol mannosyltransferase causes congenital
      disorder of glycosylation type Ik.
AB  - The molecular nature of a severe multisystemic disorder with a recurrent
      nonimmune hydrops fetalis was identified as deficiency of GDP-Man:GlcNAc(2)-PP
      dolichol mannosyltransferase, the human orthologue of the yeast ALG1 gene (MIM
      605907). The disease belongs to the group of congenital disorders of
      glycosylation (CDG) and is designated as subtype CDG-Ik. In patient-derived
      serum, the total amount of the glycoprotein transferrin was reduced. Moreover, a
      partial loss of N-glycan chains was observed, a characteristic feature of CDG
      type I forms. Metabolic labeling with [6-(3)H]glucosamine revealed an
      accumulation of GlcNAc(2)-PP-dolichol and GlcNAc(1)-PP-dolichol in skin
      fibroblasts of the patient. Incubation of fibroblast extracts with
      [(14)C]GlcNAc(2)-PP-dolichol and GDP-mannose indicated a severely reduced
      activity of the beta 1,4-mannosyltransferase, elongating GlcNAc(2)-PP-dolichol to
      Man(1)GlcNAc(2)-PP-dolichol at the cytosolic side of the endoplasmic reticulum.
      Genetic analysis of the patient's hALG1 gene identified a homozygous mutation
      leading to the exchange of a serine residue to leucine at position 258 in the
      hALG1 protein. The disease-causing nature of the hALG1 mutation for the
      glycosylation defect was verified by a retroviral complementation approach in
      patient-derived primary fibroblasts and was confirmed by the expression of wild
      type and mutant hALG1 in the Saccharomyces cerevisiae alg1-1 strain.

PMID- 14973779
TI  - X-chromosome inactivation patterns are unbalanced and affect the phenotypic
      outcome in a mouse model of rett syndrome.
AB  - Rett syndrome (RTT), a neurodevelopmental disorder affecting mostly females, is
      caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2
      (MeCP2). Although the majority of girls with classic RTT have a random pattern of
      X-chromosome inactivation (XCI), nonbalanced patterns have been observed in
      patients carrying mutant MECP2 and, in some cases, account for variability of
      phenotypic manifestations. We have generated an RTT mouse model that
      recapitulates all major aspects of the human disease, but we found that females
      exhibit a high degree of phenotypic variability beyond what is observed in human
      patients with similar mutations. To evaluate whether XCI influences the
      phenotypic outcome of Mecp2 mutation in the mouse, we studied the pattern of XCI
      at the single-cell level in brains of heterozygous females. We found that XCI
      patterns were unbalanced, favoring expression of the wild-type allele, in most
      mutant females. It is notable that none of the animals had nonrandom XCI favoring
      the mutant allele. To explore why the XCI patterns favored expression of the wild
      type allele, we studied primary neuronal cultures from Mecp2-mutant mice and
      found selective survival of neurons in which the wild-type X chromosome was
      active. Quantitative analysis indicated that fewer phenotypes are observed when a
      large percentage of neurons have the mutant X chromosome inactivated. The study
      of neuronal XCI patterns in a large number of female mice carrying a mutant Mecp2
      allele highlights the importance of MeCP2 for neuronal viability. These findings
      also raise the possibility that there are human females who carry mutant MECP2
      alleles but are not recognized because their phenotypes are subdued owing to
      favorable XCI patterns.

PMID- 14973780
TI  - Human male recombination maps for individual chromosomes.
AB  - Meiotic recombination is essential for the segregation of chromosomes and the
      formation of normal haploid gametes, yet we know very little about the meiotic
      process in humans. We present the first (to our knowledge) recombination maps for
      every autosome in the human male obtained by new immunofluorescence techniques
      followed by centromere-specific multicolor fluorescence in situ hybridization in
      human spermatocytes. The mean frequency of autosomal recombination foci was
      49.8+/-4.3, corresponding to a genetic length of 2,490 cM. All autosomal
      bivalents had at least one recombination focus. In contrast, the XY bivalent had
      a recombination focus in 73% of nuclei, suggesting that a relatively large
      proportion of spermatocytes may be at risk for nondisjunction of the XY bivalent
      or elimination by meiotic arrest. There was a very strong correlation between
      mean length of the synaptonemal complex (SC) and the number of recombination foci
      per SC. Each bivalent presented a distinct distribution of recombination foci,
      but in general, foci were near the distal parts of the chromosome, with
      repression of foci near the centromere. The position of recombination foci
      demonstrated positive interference, but, in rare instances, foci were very close
      to one another.

PMID- 14973781
TI  - The Levant versus the Horn of Africa: evidence for bidirectional corridors of
      human migrations.
AB  - Paleoanthropological evidence indicates that both the Levantine corridor and the
      Horn of Africa served, repeatedly, as migratory corridors between Africa and
      Eurasia. We have begun investigating the roles of these passageways in
      bidirectional migrations of anatomically modern humans, by analyzing 45
      informative biallelic markers as well as 10 microsatellite loci on the
      nonrecombining region of the Y chromosome (NRY) in 121 and 147 extant males from
      Oman and northern Egypt, respectively. The present study uncovers three important
      points concerning these demic movements: (1) The E3b1-M78 and E3b3-M123 lineages,
      as well as the R1*-M173 lineages, mark gene flow between Egypt and the Levant
      during the Upper Paleolithic and Mesolithic. (2) In contrast, the Horn of Africa
      appears to be of minor importance in the human migratory movements between Africa
      and Eurasia represented by these chromosomes, an observation based on the
      frequency distributions of E3b*-M35 (no known downstream mutations) and M173. (3)
      The areal diffusion patterns of G-M201, J-12f2, the derivative M173 haplogroups,
      and M2 suggest more recent genetic associations between the Middle East and
      Africa, involving the Levantine corridor and/or Arab slave routes. Affinities to
      African groups were also evaluated by determining the NRY haplogroup composition
      in 434 samples from seven sub-Saharan African populations. Oman and Egypt's NRY
      frequency distributions appear to be much more similar to those of the Middle
      East than to any sub-Saharan African population, suggesting a much larger
      Eurasian genetic component. Finally, the overall phylogeographic profile reveals
      several clinal patterns and genetic partitions that may indicate source,
      direction, and relative timing of different waves of dispersals and expansions
      involving these nine populations.

PMID- 14973782
TI  - Congenital disorder of glycosylation type Ik (CDG-Ik): a defect of
      mannosyltransferase I.
AB  - This study describes the discovery of a new inherited disorder of glycosylation
      named "CDG-Ik." CDG-Ik (congenital disorder of glycoslyation type Ik) is based on
      a defect of human mannosyltransferase I (MT-I [MIM 605907]), an enzyme necessary
      for the elongation of dolichol-linked chitobiose during N-glycan biosynthesis.
      Mutations in semiconserved regions in the corresponding gene, HMT-1 (yeast
      homologue, Alg1), in two patients caused drastically reduced enzyme activity,
      leading to a severe disease with death in early infancy. One patient had a
      homozygous point mutation (c.773C-->T, S258L), whereas the other patient was
      compound heterozygous for the mutations c.773C-->T and c.1025A-->C (E342P).
      Glycosylation and growth of Alg1-deficient PRY56 yeast cells, showing a
      temperature-sensitive phenotype, could be restored by the human wild-type allele,
      whereas only slight restoration was observed after transformation with the
      patients' alleles.

PMID- 14973784
TI  - Multiple comparisons in studies of gene x gene and gene x environment
      interaction.

PMID- 14973783
TI  - Melanocortin-4 receptor gene variant I103 is negatively associated with obesity.
AB  - Several rare mutations in the melanocortin-4 receptor gene (MC4R) predispose to
      obesity. For the most common missense variant V103I (rs2229616), however, the
      previously reported similar carrier frequencies in obese and nonobese individuals
      are in line with in vitro studies, which have not shown a functional implication
      of this variant. In the present study, we initially performed a
      transmission/disequilibrium test on 520 trios with obesity, and we observed a
      lower transmission rate of the I103 allele (P=.017), which was an unexpected
      finding. Therefore, we initiated two large case-control studies (N=2,334 and
      N=661) and combined the data with those from 12 published studies, for a total of
      7,713 individuals. The resulting meta-analysis provides evidence for a negative
      association of the I103 allele with obesity (odds ratio 0.69; 95% confidence
      interval 0.50-0.96; P=.03), mainly comprising samples of European origin.
      Additional screening of four other ethnic groups showed comparable I103 carrier
      frequencies well below 10%. Genomic sequencing of the MC4R gene revealed three
      polymorphisms in the noncoding region that displayed strong linkage
      disequilibrium with V103I. In our functional in vitro assays, the variant was
      indistinguishable from the wild-type allele, as was the result in previous
      studies. This report on an SNP/haplotype that is negatively associated with
      obesity expands the successful application of meta-analysis of modest effects in
      common diseases to a variant with a carrier frequency well below 10%. The
      respective protective effect against obesity implies that variation in the MC4R
      gene entails both loss and gain of function.

PMID- 14973786
TI  - Revisiting the clinical validity of multiplex genetic testing in complex
      diseases.

PMID- 14973788
TI  - Impact of genotyping errors on type I error rate of the haplotype-sharing
      transmission/disequilibrium test (HS-TDT).

PMID- 14973791
TI  - Perioperative medicine: NHLBI working group deliberations and recommendations.

PMID- 14973792
TI  - Cost-effectiveness of differing perioperative beta-blockade strategies in
      vascular surgery patients.
AB  - OBJECTIVES: To determine the incremental value of different strategies of both
      oral and intravenous beta-blockade during the perioperative period in high-risk
      vascular patients in reducing costs and improving outcomes. DESIGN: Decision
      analytic model incorporating costs from provider's perspective INTERVENTIONS:
      Five perioperative strategies in patients undergoing abdominal aortic aneurysm
      surgery: (1). no routine beta-blockade, (2). preoperative oral bisoprolol for 7
      days followed by perioperative intravenous metoprolol and oral bisoprolol based
      on preoperative titration, (3). immediate preoperative atenolol with
      postoperative intravenous then oral atenolol, (4). intraoperative esmolol and
      postoperative intravenous then oral atenolol, and (5). intraoperative and 18
      hours of postoperative esmolol then atenolol. MEASUREMENTS AND MAIN RESULTS:
      Perioperative death was associated with a net increase of US dollars 21909 in
      charges to Medicare, whereas sustaining a perioperative myocardial infarction was
      associated with a net increase in charges of US dollars 15000. There is a net
      hospital saving of US dollars 500 using a strategy of titration of an oral beta
      blocker medication for a minimum of 7 days, with a net increase in efficacy of
      0.0304. All of the strategies involving acute perioperative blockade were
      associated with a net cost savings and increase in efficacy, although less than
      the strategy involving preoperative oral titration. CONCLUSION: Perioperative
      beta-blockade is both cost effective as well as efficacious from a short-term
      provider perspective. The optimal strategy of treatment for patients who do not
      present to surgery already on beta-blockers requires further study, although all
      strategies save money even accounting for pharmaceutical costs.

PMID- 14973793
TI  - Perioperative beta-blockade: a survey of physician attitudes in the department of
      Veterans Affairs.
AB  - OBJECTIVE: To delineate clinician opinion on the efficacy, safety, and logistics
      of perioperative beta-adrenergic blockade for patients undergoing noncardiac
      surgery. DESIGN: Survey of opinions and clinical practices. SETTING: Internet
      based survey form. PARTICIPANTS: Members of the Associations of Veterans Affairs
      Anesthesiologists and Surgeons and chiefs of cardiology in centers with surgical
      programs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty
      seven responses from 62 Veterans Affairs Medical Centers in 35 states (57
      anesthesiologists, 45 surgeons, 25 cardiologists) were analyzed. Ninety-two
      percent agreed that it is effective in reducing short-term adverse outcomes,
      declining to 60% for long-term outcome. There was greater enthusiasm for its use
      in patients with known coronary artery disease (87%) than in patients with risk
      factors only (72%). Although 66% considered it efficacious in vascular surgery,
      only 30% were convinced it was for nonvascular surgery (with a similar
      distribution for safety in these settings). Preoperative use was favored (94%),
      with most physicians favoring use within 1 week of surgery (52%). Most favored 1
      to 2 weeks of postoperative therapy (43%), with the remainder favoring shorter
      (19%) or longer (35%) durations. Although 71% of clinicians reported frequent use
      in their practice, most believed its use was largely informal by their colleagues
      (83%) and rarely based on a formal clinical pathway (13%). CONCLUSION: A wide
      range of opinions by clinicians regarding the efficacy, safety, and logistics of
      perioperative beta-adrenergic blockade was encountered, suggesting need for
      additional clinical research and centralized efforts at increasing compliance
      with existing guidelines.

PMID- 14973794
TI  - A prospective, randomized study of endothelin and postoperative recovery in off
      pump versus conventional coronary artery bypass surgery.
AB  - OBJECTIVE: The objectives are 2-fold: (1). to serially determine endothelin (ET)
      levels in arterial vascular compartments in patients undergoing coronary artery
      bypass surgery using either cardiopulmonary bypass or off-pump techniques, and
      (2). to define potential relationships between endothelial levels and specific
      perioperative parameters of patient recovery. METHODS: In a prospective,
      randomized study, endothelin plasma content was measured from patients undergoing
      coronary artery bypass grafting using either off-pump techniques (OPCAB group, n
      = 25) or conventional cardiopulmonary bypass (CPB group, n = 25) before surgery,
      before and after coronary artery anastomosis, and 6 and 24 hours postoperatively.
      Specific indices of patient recovery including pulmonary artery pressures,
      ventilation requirement, and hospital stay were documented for patients in both
      study groups. RESULTS: Postoperative systemic arterial ET levels were
      significantly increased by 200% in the CPB group and 50% in the OPCAB group. ET
      levels remained significantly higher in the CPB group relative to the OPCAB group
      throughout the postoperative period of observation (p < 0.05). Pulmonary artery
      pressures, ventilation requirement, and hospital stay were significantly
      increased in patients in the CPB group. CONCLUSIONS: Postoperative ET levels were
      higher in patients who underwent CPB for coronary artery bypass surgery.
      Increased ET in the postoperative period may contribute to a more complex
      recovery from coronary artery bypass surgery in patients undergoing
      cardiopulmonary bypass.

PMID- 14973795
TI  - Perioperative changes in atrial natriuretic peptide plasma levels associated with
      mitral and aortic valve replacement.
AB  - OBJECTIVE: Atrial natriuretic peptide (ANP) plasma levels are increased in
      patients with valvular heart disease. The present study investigates possible
      changes after mitral or aortic valve replacement (MVR, AVR). METHODS: In this
      prospective study, ANP plasma levels were measured in 11 patients undergoing MVR
      for mitral stenosis, in 11 patients undergoing AVR for aortic valve stenosis, and
      in 6 patients without heart disease undergoing thoracotomy for lung resection
      (control group). Blood samples were collected preoperatively (1 day before),
      during, and 8 days after the operation by serial blood sampling and were
      determined by radioimmunoassay method. ANP values were correlated with the
      duration of cardiopulmonary bypass (CPB), the aortic cross-clamping time, and the
      left atrial filling pressures. RESULTS: ANP plasma levels were increased in all
      patients with valvular heart disease preoperatively and did not change during
      anesthesia or CPB; nor were they correlated with CPB duration or atrial filling
      pressures. The left atriotomy did not alter ANP plasma levels. The intracardiac
      surgical manipulations as well as CPB did not influence the ANP secretion
      intraoperatively and during the first postoperative week. Patients who underwent
      lung resection showed no change of ANP plasma levels perioperatively. CONCLUSION:
      ANP levels are not altered during and 1 week after valve replacement and,
      therefore, do not reflect hemodynamic changes perioperatively.

PMID- 14973796
TI  - Cardiac biomarker release after CABG with different surgical techniques.
AB  - OBJECTIVE: To investigate the release of cardiac biomarkers (troponin I and CK
      MB) in patients undergoing coronary artery bypass graft (CABG) with or without
      cardiopulmonary bypass (CPB). DESIGN: Prospective study. SETTING: University
      tertiary hospital. PARTICIPANTS: Sixty-five consecutive patients undergoing
      coronary artery bypass grafting (>or=2 vessel disease, ejection fraction
      >or=0.35%, elective procedure). INTERVENTIONS: Cardiac biomarkers were measured
      before surgery, at intensive care unit arrival, 4 and 18 hours after the end of
      the procedure. MEASUREMENTS AND MAIN RESULTS: Cardiac biomarker release was
      higher in on-pump than in off-pump patients at every time point. On multivariate
      analysis, CPB (p < 0.0001), number of distal grafts (p = 0.005), and hypertension
      treatment (p = 0.03) were the only independent predictors of peak cardiac
      troponin release. CONCLUSIONS: Cardiac troponin I release after multivessel CABG
      is associated with the technique. Different values for the normal range should be
      considered. OPCABG is minimally invasive for the heart as far as myocardial
      marker release is concerned.

PMID- 14973797
TI  - ECG changes after CABG: the role of the surgical technique.
AB  - OBJECTIVE: The purpose of this study was to determine whether coronary artery
      bypass grafting (CABG) surgery on the beating heart (BH) is associated with
      reduction of R-wave potentials on the precordial leads on the surface
      electrocardiogram (ECG) as previously shown for CABG with cardiopulmonary bypass.
      METHODS: Fifty-four patients undergoing CABG surgery at a single tertiary care
      university hospital were analyzed. Patients suffering a postoperative cardiac
      event (myocardial infarction) or nonspecific ECG changes were excluded. ECG
      results were recorded at arrival in the intensive care unit, after 4 and 18 hours
      postoperatively; simultaneously, myocardial cell damage biomarkers (CK-MB and
      cTnI) were assayed. A control group of 31 patients undergoing mitral valve repair
      was also evaluated. RESULTS: Patients operated with the BH (OPCABG) technique did
      not show any decrease of R-wave amplitude at 0, 4, and 18 hours postoperatively;
      whereas those operated with CPB, both for coronary artery surgery and for mitral
      repair, had a similar extent and pattern of R-wave reduction. The release of
      myocardial necrosis markers was significantly lower in coronary artery patients
      operated with BH than in those operated with CPB; however, no statistically
      significant correlation between the ECG changes and release of myocardial cell
      damage markers was observed in any of the groups. CONCLUSIONS: The findings
      indicate, for the first time, that CABG surgery on the BH is not followed by any
      reduction of R-wave amplitude on precordial leads and confirms that the BH
      technique is associated with a lower release of myocardial cell damage markers.

PMID- 14973798
TI  - Cardiac output monitoring during off-pump coronary artery bypass grafting.
AB  - OBJECTIVE: To evaluate and compare monitors of cardiac output during
      repositioning and stabilization of the heart for off-pump coronary artery bypass
      (OPCAB) surgery. DESIGN: Prospective, observational, clinical study. SETTING:
      University teaching hospital. PARTICIPANTS: Consecutive patients scheduled to
      undergo elective OPCAB (n = 19). INTERVENTIONS: Monitoring, induction, and
      anesthesia followed a routine protocol for coronary artery bypass patients. This
      included the use of transesophageal echocardiography (TEE) and pulmonary artery
      catheter placement. MEASUREMENTS AND MAIN RESULTS: After positioning and
      stabilization for OPCAB surgery, the changes in descending aortic flow velocity
      (VTI) times heart rate (HR) and the mixed venous oxygen saturation (SvO(2)) could
      be used to predict the changes in thermodilution cardiac output (TDCO) using the
      following model: deltaTDCO((calc))=-13.15+0.35(deltaVTI*HR)+0.61(deltaSvO(2))
      where Delta indicates the percentage change from baseline values. The changes in
      mean arterial pressure, mean pulmonary artery pressure, and continuous cardiac
      output did not correlate with the changes in TDCO. CONCLUSION: The use of the
      VTI*HR, as determined by TEE, in addition to the SvO(2) can strengthen clinical
      decision making during repositioning and stabilization of the heart during OPCAB.
      Changes in the VTI*HR and SvO(2) can be used as surrogate markers for changes in
      CO during OPCAB surgery.

PMID- 14973799
TI  - Noninvasive measurement of intrapulmonary shunting.
AB  - OBJECTIVE: To investigate the accuracy and precision of a noninvasive approach to
      measurement of pulmonary shunt fraction using simultaneous application of 2
      fundamental respiratory mixing equations: the direct Fick equation for oxygen and
      the shunt equation of Berggren. This can be performed without mixed venous blood
      sampling and requires measurement of oxygen uptake and pulmonary blood flow.
      DESIGN: Comparison with invasive shunt fraction measured using mixed venous blood
      sampling and with estimated shunt fraction using an assumed arteriovenous O(2)
      content difference. SETTING: Major teaching hospital. PARTICIPANTS: Nine patients
      undergoing anesthesia for cardiac surgery. INTERVENTIONS: Pulmonary blood flow
      was measured using an indirect Fick technique (nitrous oxide throughflow) and by
      bolus thermodilution for comparison. MEASUREMENTS AND MAIN RESULTS: The mean
      shunt fraction measured by the invasive method was 0.145 (range 0.057-0.263).
      When pulmonary blood flow was measured using an indirect Fick technique (nitrous
      oxide throughflow), the absolute mean bias for noninvasive shunt fraction was 
      0.005 with a standard deviation of 0.012. Correlation was excellent (r(2) = 0.95,
      p < 0.001). Agreement was less precise when pulmonary blood flow was measured
      using thermodilution (mean bias + 0.001 with a standard deviation of 0.018).
      CONCLUSIONS: The noninvasive method is an accurate substitute for invasive shunt
      fraction measurement with mixed venous blood sampling.

PMID- 14973800
TI  - The effect of intravenous quinaprilat on plasma cytokines and hemodynamic
      variables during cardiac surgery.
AB  - OBJECTIVES: Perioperative treatment with angiotensin-converting enzyme (ACE)
      inhibitors in cardiac surgery with cardiopulmonary bypass is still controversial.
      Using ACE inhibitors during cardiac surgery might be associated with an increased
      risk of critical hypotensive episodes. On the other hand, ACE inhibitors could
      have beneficial effects with respect to the development of the systemic
      inflammatory response syndrome. DESIGN: The effect of acute administration of
      quinaprilat on hemodynamic variables and plasma cytokines was assessed under
      double-blind, randomized, and placebo-controlled conditions. SETTING: Department
      of anesthesiology and cardiovascular surgery clinic in a university hospital.
      PARTICIPANTS: Forty patients without preexisting cardiac failure, undergoing
      coronary artery bypass grafting. INTERVENTIONS: Patients received 0.08 mg/kg of
      intravenous quinaprilat or intravenous isotonic saline solution after induction
      of anesthesia. MEASUREMENTS AND RESULTS: Blood samples were taken after induction
      of anesthesia (T0), before cardiopulmonary bypass (T1), at the end of surgery
      (T2), and 4 hours after the end of surgery (T3). There was no difference between
      the 2 groups regarding mean arterial pressure and inotropic or vasopressor
      support. Systemic vascular resistance index was significantly lower in the
      quinaprilat group at T2 (p = 0.016) and T3 (p = 0.017). No difference in
      proinflammatory cytokine levels was observed between the 2 groups. CONCLUSIONS:
      The present investigation shows that acute administration of an intravenous ACE
      inhibitor, quinaprilat, has no influence on proinflammatory cytokines during
      cardiac surgery with cardiopulmonary bypass. The patients treated with
      quinaprilat showed an improved systemic vascular resistance index with no
      increased risk of deleterious hemodynamic episodes.

PMID- 14973801
TI  - Postoperative intravenous iron used alone or in combination with low-dose
      erythropoietin is not effective for correction of anemia after cardiac surgery.
AB  - OBJECTIVES: The aim of this study was to examine whether intravenous iron III
      hydroxide sucrose complex (IHSC) used alone was sufficient to provide rapid
      correction of anemia after cardiac surgery and whether additional stimulation of
      erythropoiesis is possible by means of a single low dose of recombinant-human
      erythropoietin (r-HuEPO) administration. DESIGN: Prospective, randomized, double
      blind study. SETTING: The study was conducted in a university hospital.
      PARTICIPANTS: One hundred twenty American Society of Anesthesiologists II or III
      patients, who underwent elective cardiac surgery using cardiopulmonary bypass and
      in whom postpump hemoglobin ranged between 7 and 10 g/dL. INTERVENTIONS: Patients
      were divided into 3 groups: group I = control; group II received postoperative
      intravenous iron supplementation with an iron III-hydroxide sucrose complex
      (IHSC); and group III received IV iron and a single dose of r-HuEPO (300 U/kg).
      MEASUREMENTS AND RESULTS: No significant difference in transfusion needs was
      observed among the 3 groups (22%, 25%, and 17% of patients transfused in groups
      I, II, and III, respectively). Hemoglobin levels, reticulocyte counts, and serum
      ferritin levels were evaluated at different time intervals (until day 30
      postoperatively). No side effects because of iron administration were noted in
      the study. Reticulocyte counts increased rapidly at day 5 (2.24% +/- 1.11%, 1.99%
      +/- 1.44%, and 3.84% +/- 2.02% in groups I, II, and III, respectively) and
      decreased after day 15 in the 3 groups. Ferritin levels increased significantly
      at day 5 in the 2 treated groups (899.33 +/- 321.55 ng/mL in group II, 845.75 +/-
      289.96 ng/mL in group III v 463.15 +/- 227.74 ng/mL in group I). In group I,
      ferritin levels, after a slight elevation on day 5, decreased at day 15 to lower
      than baseline levels. No significant difference in hemoglobin increase was noted
      among the 3 groups. CONCLUSION: Postoperative intravenous iron supplementation
      alone or in combination with a single dose of r-HuEPO (300 U/kg) is not effective
      in correcting anemia after cardiac surgery.

PMID- 14973802
TI  - Similar pain scores after early and late extubation in heart surgery with
      cardiopulmonary bypass.
AB  - OBJECTIVE: To investigate if early extubation, 2 hours after surgery, would
      result in more postoperative pain or in an increased use of opioid analgesics
      compared with late extubation, 6 hours after surgery. DESIGN: Prospective,
      randomized study. SETTING: Intensive care unit, university hospital.
      PARTICIPANTS: Sixty patients undergoing cardiac surgery with cardiopulmonary
      bypass. INTERVENTIONS: Patients were randomized into 2 groups: extubation at
      about 2 (early) or 6 (late) hours. Anesthesia was based on propofol and
      remifentanil. There was no epidural analgesia and no local anesthesia in the
      wound. A bolus of the opioid ketobemidone was administered toward the end of
      surgery followed by a continuous infusion. MEASUREMENTS AND MAIN RESULTS: Pain,
      provoked during deep breathing or coughing, evaluated with a visual analog scale
      (VAS) going from 0 to 10, was measured after extubation, and at 8 and 16 hours
      after surgery. Unprovoked pain was measured hourly. If VAS was greater than 3,
      the infusion rate was increased and a bolus of ketobemidone was given. Three
      patients in the late group were excluded because of incomplete data. Pain did not
      differ between the early and late groups at any time. In all patients, 21 never
      scored >3, 11 scored >3 once, and 25 scored >3 more than once. Nine patients had
      1 score >5. The amount of ketobemidone was similar in both groups. CONCLUSIONS:
      Early extubation had no negative effect on the quality of postoperative pain
      control and was not followed by an increased use of analgesics.

PMID- 14973803
TI  - Acupressure wristbands for the prevention of postoperative nausea and vomiting in
      adults undergoing cardiac surgery.
AB  - OBJECTIVE: To determine whether the application of acupressure bands would lead
      to a reduction in postoperative nausea and vomiting after cardiac surgery.
      DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: University
      affiliated tertiary care teaching hospital. PARTICIPANTS: Adult patients
      undergoing cardiac surgery. INTERVENTIONS: One hundred fifty-two patients were
      enrolled to receive either acupressure treatment (n = 75) or placebo (n = 77).
      All patients had acupressure bands placed on both wrists before induction of
      anesthesia; those in the treatment group had a bead placed in contact with the P6
      point on the forearm. MEASUREMENTS AND MAIN RESULTS: Patients were assessed for
      nausea, vomiting, and pain scores during the first 24 hours of the postoperative
      period. The incidences of nausea, vomiting, pain scores, and analgesic and
      antiemetic requirements were similar between the 2 groups. A subgroup analysis by
      gender implied that acupressure treatment may be effective only in female
      patients. CONCLUSION: Acupressure treatment did not lead to a reduction in
      nausea, vomiting, or antiemetic requirements in patients after cardiac surgery.

PMID- 14973804
TI  - Interruption of gravity-driven carrier fluid infusing through a pulmonary artery
      catheter venous infusion port.

PMID- 14973805
TI  - Extravascular placement of a central venous catheter in the mediastinum.

PMID- 14973806
TI  - Esophageal mucosal tear from a transesophageal echocardiography probe despite
      preliminary assessment via esophagoscopy in a patient with esophageal disease.

PMID- 14973807
TI  - Delayed-onset adrenal insufficiency after cardiac surgery despite perioperative
      steroid supplementation.

PMID- 14973808
TI  - Reduction of bispectral index value associated with clinically significant
      cerebral air embolism.

PMID- 14973809
TI  - Transmyocardial laser revascularization.

PMID- 14973810
TI  - Heparin is much more than just an anticoagulant.

PMID- 14973811
TI  - CASE 1--2004. Intraoperative diagnosis of a patent foramen ovale in a patient
      undergoing coronary artery bypass graft surgery.

PMID- 14973814
TI  - Pro: intraoperative transesophageal echocardiography is of utility in patients at
      high risk of adverse cardiac events undergoing noncardiac surgery.

PMID- 14973815
TI  - Con: intraoperative transesophageal echocardiography is not of utility in
      patients at high risk of adverse cardiac events undergoing noncardiac surgery.

PMID- 14973816
TI  - Bubble trouble.

PMID- 14973817
TI  - Incidental transesophageal echocardiographic findings of a mass on the aortic
      valve.

PMID- 14973819
TI  - Inadvertent intravenous administration of a high dose of ephedrine.

PMID- 14973820
TI  - Propofol infusion into the pump during cardiopulmonary bypass: is it safe and
      effective?

PMID- 14973821
TI  - Massive epistaxis after nasopharyngeal temperature probe insertion after cardiac
      surgery.

PMID- 14973854
TI  - Mobile- vs. fixed-bearing total knee arthroplasty: a clinical and radiologic
      study.
AB  - A consecutive series of patients undergoing total knee arthroplasty (TKA) using
      either a mobile-bearing (MB) or a fixed-bearing (FB) implant were studied. Forty
      four patients received 57 MB rotating platforms, and 40 patients received 45 FB
      posterior stabilized implants. At an average 41-month follow-up (range, 2-6
      years), no significant differences were found between the groups with respect to
      Knee Society ratings or pain scores. Postoperative flexion was not different
      between the groups (116 degrees for MB and 118 degrees for FB). Three MB knees
      were revised for implant-related complications. There was no difference between
      these MB or FB knee implants clinically or radiographically at early follow-up.
      However, more patients with a MB knee required early revision for failure of
      rotating patellar or tibial polyethylene implants.

PMID- 14973855
TI  - Long-stem cemented calcar replacement arthroplasty for proximal femoral bone
      loss.
AB  - Revision total hip arthroplasty with accompanying bone defects may require calcar
      replacement prostheses to restore hip stability and function. Twenty-nine hips in
      27 patients were followed for a mean of 41 months (range, 24-101 months). The
      average Harris Hip Score increased from 34 to 82 points. Acceptable cement
      mantles (A, B, C1) were present in all cases. Three femoral components (10.3%)
      were re-revised as a result of aseptic loosening. Two others (6.9%) were loose by
      radiographic criteria. Thus, 24 (82.8%) of the 29 index femoral components were
      rigidly fixed according to radiographic criteria, whereas 26 (89.7%) still were
      in place at the time of review. The results of this study suggest that long-stem
      cemented calcar-replacement prostheses with modern cementing technique are a
      reasonable option in femoral revision arthroplasties involving proximal bone
      loss.

PMID- 14973856
TI  - Primary total hip arthroplasty with an uncemented femoral component: a long-term
      study of the Taperloc stem.
AB  - The purpose of the current study was to evaluate the long-term result of a
      tapered, uncemented femoral component. We retrospectively reviewed the clinical
      and radiographic records of 121 patients (129 hips) who underwent primary total
      hip arthroplasty with the use of the Taperloc uncemented stem. Follow-up averaged
      11 years (range, 6-15 years). The mean Harris Hip Score at the latest follow-up
      was 92.1. Thigh pain was reported in 5 patients (3.6%). One stem was revised at 6
      years because of severe proximal femoral osteolysis. There was no evidence of
      radiographic subsidence or loosening around any stems. The overall medium- to
      long-term outcome of the Taperloc stem is excellent, with a low revision rate and
      high patient satisfaction.

PMID- 14973857
TI  - Recurrent hemarthrosis after knee joint arthroplasty: etiology and treatment.
AB  - This study reports the results for 10 patients with recurrent hemarthrosis after
      knee joint arthroplasty. The average interval between arthroplasty and the first
      instance of hemarthrosis was at 26 months, and the average number of hemarthroses
      per patient was 3.8. In 3 patients, the bleeding responded to simple conservative
      measures. The remaining 7 needed surgery; there were 6 arthroscopic synovectomies
      and 1 polyethylene revision. Impingement of the proliferative synovium was
      observed in only 2 patients during surgical intervention. In the 2 patients in
      whom arthroscopic management was successful, another procedure with an electric
      coagulator, in addition to a formal synovectomy, was performed. The use of a
      coagulator may be helpful for direct coagulation when arthroscopic management is
      selected, although open synovectomy is curative in most cases.

PMID- 14973858
TI  - Influence of component positions on dislocation: computed tomographic evaluations
      in a consecutive series of total hip arthroplasty.
AB  - Component positions in a consecutive series of total hip arthroplasty through a
      posterolateral approach without capsular and external rotator repair, using the
      same prosthesis type, head size, and liner, were evaluated using computed
      tomography, and correlation with occurrence of postoperative dislocation was
      assessed. The 9 hips with posterior dislocation had significantly lower cup
      anteversion than the 181 hips without dislocation. Seven (78%) of the 9 hips with
      posterior dislocation had cup anteversion <20 degrees, irrespective of stem
      anteversion. These findings suggest that among variables of component positions,
      cup anteversion is one of the important factors for risk of dislocation, and that
      intentionally placing the cup at low anteversion to compensate for high femoral
      neck anteversion may predisposes the hip to postoperative dislocation.

PMID- 14973859
TI  - The results of tibial tubercle osteotomy for revision total knee arthroplasty.
AB  - Tibial tubercle osteotomy was used in the surgical exposure of 67 knees in 64
      patients undergoing revision total knee arthroplasty. The clinical and
      radiographic results were reviewed retrospectively. The mean follow-up time was
      30 months (range, 5-60 months). Knee Society scores (KSS) confirmed good or
      excellent results in 87% of the knees, and the mean KSS was 86. The procedure was
      particularly effective in 2-stage exchanges for infected total knee arthroplasty,
      in which infection was eradicated in 9 of 10 cases, with a mean KSS of 82. In
      this series, no patellofemoral complications, no component malalignments, and no
      avulsions of the patellar tendon occurred. Serious complications directly related
      to the tibial tubercle osteotomy occurred in 5 patients (7%).

PMID- 14973860
TI  - Displaced femoral neck fractures in the elderly: disposition and outcome after 3-
      to 6-year follow-up evaluation.
AB  - This study evaluated the relationship of the disposition and outcome of patients
      with displaced femoral neck fractures with the type of surgical treatment. From
      1993 to 1996, 186 patients with displaced femoral neck fractures who were 65
      years of age or older were treated at one hospital. One hundred and twenty
      fractures were treated with reduction and internal fixation; 66 were treated with
      arthroplasty. The time interval from fracture to death and to repeat surgery was
      significantly less for the internal fixation group than for the arthroplasty
      group. The possibility of nursing home residence is increased in patients who
      were treated with reduction and internal fixation compared with patients who were
      treated with arthroplasty.

PMID- 14973861
TI  - Economic evaluation in total hip arthroplasty: analysis and review of the
      literature.
AB  - We performed a bibliographic search of MEDLINE databases from January 1966 to
      July 2002 to identify English language articles that contained either "cost" or
      "economic" in combination with "total hip arthroplasty" (THA) in the abstract or
      title. Each study was then critically reviewed for content, technique, and
      adherence to established healthcare economic principles. Only 81 of the 153
      studies retrieved contained actual economic data. Only 6% of studies adhered to
      established criteria for a comprehensive health care economic analysis. Although
      the number of publications regarding economic evaluation of THA is on the rise,
      the methodologic quality of many of these studies remains inadequate. Future
      studies should employ sound healthcare economic techniques to properly evaluate
      and assess the true social and economic value of THA.

PMID- 14973862
TI  - Total knee arthroplasty in Ehlers-Danlos syndrome.
AB  - The Ehlers-Danlos syndromes (EDS) are a rare group of connective tissue disorders
      characterized by severe joint hypermobility and instability. Ten patients with 12
      primary knee arthroplasties were identified. Average age at time of surgery was
      43.3 years, with follow-up data acquired at an average of 65 months after
      surgery. Primary indications for surgery were tibiofemoral or patellar
      instability (n = 8) and arthritis (n = 4). Knee Society Functional scores
      averaged 29.6 before surgery and 51.3 at time of interview (P<.005). Knee Society
      Knee scores at time of follow-up evaluation averaged 70. Tibiofemoral and patella
      stability were significantly improved. Arthroplasty appears to be an effective
      option for knee arthritis and instability in EDS patients, although results and
      satisfaction are lower than that reported for conventional arthroplasty
      indications.

PMID- 14973863
TI  - Primary total hip arthroplasty using a modular proximally coated prosthesis in
      patients older than 70: two to eight year results.
AB  - Patients older than 70 years who underwent primary total hip arthroplasty using a
      modular proximally porous-coated femoral stem with an ingrowth hemispherical
      acetabular component were evaluated. This included 135 hips in 122 patients, with
      an average 5-year follow-up period. This study included 96 patients (107 hips)
      still living; 26 patients (28 hips) patients had died, and 8 patients were lost
      to follow up. In this study, 93% of patients had little or no pain, and 95% were
      extremely or very satisfied with the operation. Mean Harris Hip score was 83,
      with a Short Form-36 (SF-36) physical component and mental component summary
      score of 41 and 51, respectively. Osteolysis surrounding the femur was seen in 8
      hips (7%) and around the acetabulum in 6 hips (5%). No components were loose or
      required revision.

PMID- 14973864
TI  - Mechanical strength of repairs of the hip piriformis tendon.
AB  - Mechanical properties of repairs of the piriformis tendon to the proximal femur
      were examined in a cadaveric model. Four constructs were separately tested: a
      suture anchor in the proximal femur, the anchor to suture interface, the suture
      in tendon interface, and a bone bridge style repair. The weakest interface was
      the anchor in the bone in cases in which the bone quality was poor. In specimens
      with high bone quality, the weakest interface was the suture in the anchor. A
      positive correlation was seen between Singh score for each femur and failure load
      of the anchor-bone constructs. Therefore, repairing the short external rotators
      after procedures involving a posterior approach to the hip may be warranted in
      patients with good bone quality.

PMID- 14973865
TI  - Evaluation of knee and hindfoot alignment before and after total knee
      arthroplasty: a prospective analysis.
AB  - A prospective study on 100 cases was performed to evaluate the effect of total
      knee arthroplasty (TKA) on hindfoot alignment, and to compare knee alignment and
      hindfoot alignment preoperatively and postoperatively. Preoperative knee
      alignment ranged from 30 degrees of valgus to 13 degrees of varus. Postoperative
      knee alignment ranged from 14 degrees of valgus to 0 degrees. Preoperative foot
      alignment ranged from 22 degrees of valgus to 13 degrees of varus. Postoperative
      foot alignment ranged from 22 degrees of valgus to 11 degrees of varus.
      Preoperative knee alignment did not correlate with foot alignment (P =.182).
      Postoperative knee alignment and foot alignment also showed no correlation (P
      =.222). Preoperative and postoperative knee alignment were correlated, as
      expected (P =.000). Notably, hindfoot alignment was changed by knee arthroplasty,
      and changed in a predictable fashion (P=.000). The alignment of the foot before
      knee arthroplasty was the largest contributing factor to the hindfoot alignment
      after arthroplasty of the knee. Hindfoot alignment was changed by TKA, and
      changed in a predictable fashion.

PMID- 14973866
TI  - An in vivo biomechanical analysis of the soft-tissue envelope of osteoarthritic
      knees.
AB  - Soft-tissue balancing and the amount of tension applied to the ligaments in a
      well-functioning total knee arthroplasty (TKA) has, thus far, not been accurately
      quantified. A ligament-tensioning device was used to measure displacement between
      the tibia and femur versus load during 86 consecutive TKAs. Measurements were
      made in flexion and extension following bone cuts and final soft-tissue balancing
      to calculate mean effective stiffness (MES) of the soft-tissue envelope and mean
      resting force on the implanted polyethylene component. MES was not affected by
      age or gender and did not differ in flexion versus extension. MES was
      significantly higher in posterior cruciate-retaining knees compared with
      posterior cruciate-sacrificing knees. There was no statistical difference between
      mean resting force on the polyethylene in flexion versus extension, or in
      posterior cruciate-retaining versus -sacrificing knees. These biomechanical data
      will serve as a good starting point for which to compare the expected stiffness
      of the ligaments and resting load on the polyethylene in well-balanced knees.

PMID- 14973867
TI  - Function of the anterior cruciate ligament after unicompartmental knee
      arthroplasty: an in vitro robotic study.
AB  - The objective of this study was to investigate the role of the anterior cruciate
      ligament (ACL) in the anterior-posterior (AP) stability of the knee after
      unicompartmental knee arthroplasty (UKA). AP tibial loads were applied to human
      cadaveric knee specimens using a robotic testing system. After UKA, the knee
      exhibited tibial translations similar to that of the native knee, and the forces
      in the ACL were also similar to those seen in the native knee. The ACL-deficient
      knee after UKA exhibited significantly greater anterior tibial translations than
      the native knee and the knee after UKA with an intact ACL. These data suggest
      that medial UKA does not alter the anterior stability of the knee, but a
      functional ACL is necessary to ensure normal stability after UKA.

PMID- 14973868
TI  - The pumping of fluid in cementless cups with holes.
AB  - Ten patients who were scheduled for revision for pelvic osteolysis were studied.
      All had bone-ingrown metal-backed cups with holes and polyethylene liners.
      Pressures were measured in the osteolytic lesion and in the hip joint while
      applying cyclic forces across the artificial joint. In 4 cases with lesions that
      were fully contained by bone, loading of the hip produced a pressure wave in the
      osteolytic lesion. Cyclic forces, such as those that occur in normal gait, can
      act on the polyethylene liner, the metal shell, and the supporting bone to pump
      fluid in the retroacetabular osteolytic lesion. This pumping action may
      contribute to the pathogenesis of osteolysis by the mechanisms of fluid pressure,
      fluid flow, or the transportation of wear particles.

PMID- 14973869
TI  - Cutaneous neoplasm arising from total knee replacement incision in the early
      postoperative period.
AB  - Potential wound healing complications after total knee arthroplasty includes
      infection, skin edge necrosis, and dehiscence. We report another type of wound
      problem: the rapid development of a skin malignancy (or premalignancy) along an
      immature scar after knee arthroplasty.

PMID- 14973870
TI  - Failure of a new constrained acetabular insert: a report of 2 cases.
AB  - A new constrained total hip arthroplasty (THA) is currently in use. We report on
      one patient with 2 failed Trilogy constrained acetabular liners in the same hip
      (Zimmer, Warsaw, IN). We are not aware of any other published reports concerning
      failure of this implant. Both times, the constrained THA seems to have been
      properly assembled. Impingement of the modular femoral head skirt on the
      polyethylene liner appears to have caused the reinforcing ring to disengage and
      the THA to dislocate. Skirted modular femoral heads should probably not be used
      with this implant.

PMID- 14973871
TI  - Displacement of a cemented socket after reduction of a dislocated total hip
      arthroplasty.
AB  - Acute displacement of the cemented acetabular component of a hip arthroplasty
      after attempted reduction of a dislocation is described. The causes of
      displacement of the socket, which was not radiologically loose, are discussed.
      Potential causes include impingement of the femoral head and the ceramic screw
      head overhanging the acetabular bone, which was used to fix the bone graft.

PMID- 14973872
TI  - Acute pasteurella multocida in total knee arthroplasty.
AB  - Pasturella multocida is a rare cause of joint sepsis in total joint arthroplasty,
      and all case reports have identified a distant source of infection from an animal
      bite that has caused potential hematogenous seeding of the prosthesis. We report
      a case in which no potential distal wound source was found and the only likely
      etiology was local wound seeding from an old injury. In that injury, a saddle
      stirrup had caused a severe traumatic soft tissue injury as a horse had rolled
      over the patient. We draw attention to the fact that this particular bacteria is
      virulent in producing septic contamination of a total joint prosthesis, and
      aggressive treatment is indicated when such infection is identified.

PMID- 14973873
TI  - Candidal prosthetic hip infection in a patient with previous candidal septic
      arthritis.
AB  - We describe the case of a patient with chronic monocytic leukemia who underwent
      total hip arthroplasty (THA) for hip arthrosis. The patient has a history of
      Candida albicans arthritis of the same joint 5 months before THA surgery. Seven
      months after the prosthetic joint surgery, the patient developed a C albicans
      prosthetic infection that was successfully treated with amphotericin B and
      prosthesis removal. At surgery, the patient was believed cured of the candidal
      infection. Risk of infection after prosthetic joint surgery in patients with
      previous fungal joint infections has not been fully investigated. A lengthy
      infection-free follow-up period is probably necessary but may not be sufficient
      to prevent the occurrence of postoperative infections in these patients.

PMID- 14973944
TI  - Acupuncture for chronic asthma.
AB  - BACKGROUND: Acupuncture has traditionally been used to treat asthma in China and
      is used increasingly for this purpose internationally. OBJECTIVES: The objective
      of this review was to assess the effects of acupuncture for the treatment of
      asthma or asthma-like symptoms. SEARCH STRATEGY: We searched the Cochrane Airways
      Group trials register (searched August 2003), the Cochrane Complementary Medicine
      Field trials register, the Alternative Medicine Database (August 2003) and
      reference lists of articles. We also contacted trialists and researchers in the
      field of complementary and alternative medical research. SELECTION CRITERIA:
      Randomised and possibly randomised trials using needle acupuncture or other forms
      of stimulation of acupuncture. Any form of control treatment was considered (no
      treatment in addition to conventional asthma treatment, sham or placebo
      interventions, active comparator interventions). Studies were included provided
      outcome was assessed at one week or more. DATA COLLECTION AND ANALYSIS: At least
      two reviewers independently assessed trial quality. A reviewer experienced in
      acupuncture assessed the adequacy of the active and sham acupunctures used in the
      studies. Study authors were contacted for missing information. MAIN RESULTS:
      Eleven studies met the inclusion criteria with 324 participants. Trial reporting
      was poor and trial quality was deemed inadequate to generalise findings. There
      was variation in the type of active and sham acupunctures, the outcomes measured
      and time-points presented. The points used in the sham arm of some studies are
      used for the treatment of asthma according to traditional Chinese medicine. Two
      studies used individualised treatment strategies and one study used a combination
      strategy of formula acupuncture with the addition of individualised points. No
      statistically significant or clinically relevant effects were found for
      acupuncture compared to sham acupuncture. Data from two small studies were pooled
      for lung function (post-treatment FEV1): Standardised Mean Difference 0.12, 95%
      confidence interval -0.31 to 0.55). REVIEWER'S CONCLUSIONS: There is not enough
      evidence to make recommendations about the value of acupuncture in asthma
      treatment. Further research needs to consider the complexities and different
      types of acupuncture.

PMID- 14973945
TI  - Antibiotic prophylaxis to reduce respiratory tract infections and mortality in
      adults receiving intensive care.
AB  - BACKGROUND: Pneumonia is an important cause of mortality in intensive care units.
      The incidence of pneumonia in such patients ranges between 7% and 40%, and the
      crude mortality from ventilator associated pneumonia may exceed 50%. Although not
      all deaths in patients with this form of pneumonia are directly attributable to
      pneumonia, it has been shown to contribute to mortality in intensive care units
      independently of other factors that are also strongly associated with such
      deaths. OBJECTIVES: The objective of this review was to assess the effects of
      antibiotics for preventing respiratory tract infections and overall mortality in
      adults receiving intensive care. SEARCH STRATEGY: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL) (issue 3, 2003), which contains
      the Acute Respiratory Infections (ARI) Group specialised trials register; MEDLINE
      (January 1966 to September 2003); EMBASE (January 1990 to September 2003);
      proceedings of scientific meetings and reference lists of articles from January
      1984 to December 2002. We also contacted investigators in the field. SELECTION
      CRITERIA: Randomised trials of antibiotic prophylaxis for respiratory tract
      infections and deaths among adult intensive care unit patients. DATA COLLECTION
      AND ANALYSIS: At least two reviewers independently extracted data and assessed
      trial quality. MAIN RESULTS: Overall 36 trials involving 6922 people were
      included. There was variation in the antibiotics used, patient characteristics
      and risk of respiratory tract infections and mortality in the control groups. In
      17 trials (involving 4295 patients) that tested a combination of topical and
      systemic antibiotic, the average rates of respiratory tract infections and deaths
      in the control group were 36% and 29% respectively. There was a significant
      reduction of both respiratory tract infections (odds ratio 0.35, 95% confidence
      interval 0.29 to 0.41) and total mortality (odds ratio 0.78, 95% confidence
      interval 0.68 to 0.89) in the treated group. On average 5 patients needed to be
      treated to prevent one infection and 21 patients to prevent one death. In 17
      trials (involving 2664 patients) that tested topical antimicrobials alone (or
      comparing topical plus systemic versus systemic alone) the rates of respiratory
      tract infections and deaths in the control groups were 30% and 26% respectively.
      There was a significant reduction of respiratory tract infections (odds ratio
      0.52, 95% confidence interval 0.43 to 0.63) but not in total mortality (odds
      ratio 0.97, 95% confidence interval 0.81 to 1.16) in the treated group.
      REVIEWER'S CONCLUSIONS: A combination of topical and systemic prophylactic
      antibiotics reduces respiratory tract infections and overall mortality in adult
      patients receiving intensive care. A treatment based on the use of topical
      prophylaxis alone reduces respiratory infections but not mortality. The risk of
      occurrence of resistance as a negative consequence of antibiotic use was
      appropriately explored only in the most recent trial by de Jonge which did not
      show any such effect.

PMID- 14973946
TI  - Gamma and other cephalocondylic intramedullary nails versus extramedullary
      implants for extracapsular hip fractures.
AB  - BACKGROUND: Cephalocondylic intramedullary nails, which are inserted proximally
      to distally (cephalocondylic), have been used for the surgical treatment of
      extracapsular hip fractures. OBJECTIVES: To compare all cephalocondylic
      intramedullary nails with extramedullary implants for the surgical treatment of
      extracapsular hip fractures in adults. This is the fourth substantive update of
      our original review which compared the Gamma nail with the sliding hip screw
      (SHS). SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group
      trials register, MEDLINE, several orthopaedic journals and conference
      proceedings, and reference lists of relevant articles. We contacted trialists,
      colleagues and implant manufacturers. Date of the most recent search: May 2003.
      SELECTION CRITERIA: All randomised and quasi-randomised trials comparing
      cephalocondylic nails with extramedullary implants for extracapsular hip
      fractures. DATA COLLECTION AND ANALYSIS: Both reviewers independently assessed
      trial quality and extracted data. Additional information was sought from all
      trialists. Wherever appropriate and possible, results were pooled. MAIN RESULTS:
      Eighteen trials comparing the Gamma nail with the SHS were included, with data
      available for 2575 patients. The Gamma nail was associated with an increased risk
      of operative and later fracture of the femur and an increased re-operation rate.
      There were no major differences in the incidence of wound infection, mortality or
      medical complications between implants. Data were inadequate for other outcomes.
      Five trials involving 623 patients compared the intramedullary hip screw (IMHS)
      with the SHS. Fracture fixation complications were more common in the IMHS group:
      all cases of operative and later fracture of the femur occurred in this group.
      Results for post-operative complications, mortality and functional outcomes were
      similar in the two groups. One trial of 206 patients with a trochanteric fracture
      showed no advantages for proximal femoral nail (PFN) compared with the SHS. One
      trial of 60 patients reported favourable preliminary results for an experimental
      mini-invasive static intramedullary nail compared with the SHS. One trial of 230
      patients, which compared the Kuntscher-Y nail with the SHS, reported no major
      difference in outcome aside from a significantly increased number of patients
      with leg shortening, and a tendency for poorer recovery of mobility in the
      Kuntscher-Y nail group. Two trials, involving 65 patients with reverse and
      transverse fractures at the level of the lesser trochanter, compared an
      intramedullary nail (Gamma or PFN nail) with an extramedullary implant (a 90
      degree blade plate or dynamic condylar plate). The intramedullary nails were
      associated with better intra-operative results and fewer fracture fixation
      complications for these rare fractures. REVIEWER'S CONCLUSIONS: Given the lower
      complication rate of the SHS in comparison with intramedullary nails, it appears
      that the SHS is superior for trochanteric fractures. Further studies are required
      to determine if different types of intramedullary nail produce similar results,
      or if intramedullary nails have advantages for selected fracture types (for
      example, reversed fracture lines and subtrochanteric fractures).

PMID- 14973947
TI  - Treatment of latent tuberculosis infection in HIV infected persons.
AB  - BACKGROUND: Individuals with HIV infection are at an increased risk of developing
      active tuberculosis. It is known that treatment of latent tuberculosis infection
      (LTBI), also referred to as preventive therapy or chemoprophylaxis, helps to
      prevent progression to active disease in human immunodeficiency virus (HIV)
      negative populations. However, the extent and magnitude of protection (if any)
      associated with preventive therapy in those infected with HIV should be
      quantified. OBJECTIVES: To determine the effectiveness of tuberculosis preventive
      therapy in reducing the risk of active tuberculosis and death in persons infected
      with HIV. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register
      (CCTR), MEDLINE, EMBASE, AIDSLINE, AIDSTRIALS and AIDSDRUGS. We also scanned
      reference lists of articles and contacted authors and other researchers in the
      field. SELECTION CRITERIA: We included studies in which HIV positive individuals
      were randomly allocated to preventive therapy for TB and placebo, or to
      alternative TB preventive therapy regimens. Participants could be tuberculin skin
      test positive or negative, but without active tuberculosis. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently applied study selection criteria, assessed
      study quality and extracted data. Effects were assessed using relative risk for
      dichotomous data and weighted mean difference for continuous data. MAIN RESULTS:
      11 trials were included with a total of 8,130 randomized participants. Preventive
      therapy (any anti-TB drug) versus placebo was associated with a lower incidence
      of active tuberculosis (RR 0.64, 95% CI 0.51 to 0.81). This benefit was more
      pronounced in individuals with a positive tuberculin skin test (RR 0.38, 95% CI
      0.25 to 0.57) than in those who had a negative test (RR 0.83, 95% CI 0.58 to
      1.18.). Limited data suggest that the initial protective effect against
      tuberculosis may decline over the short to medium term. Efficacy was similar for
      all regimens (regardless of drug type, frequency or duration of treatment).
      However, compared to INH monotherapy, short -course multi-drug regimens were much
      more likely to require discontinuation of treatment due to adverse effects.
      Overall, there was no evidence that preventive therapy versus placebo reduced all
      cause mortality (RR 0.95, 95% CI 0.85 to 1.06), although a favourable trend was
      found in people with a positive tuberculin test (RR 0.80, 95% CI 0.63 to 1.02).
      REVIEWER'S CONCLUSIONS: Treatment of latent tuberculosis infection (LTBI) reduces
      the risk of active tuberculosis in HIV positive individuals with a positive
      tuberculin skin test. The choice of regimen will depend on factors such as cost,
      adverse effects, adherence and drug resistance. Future studies should assess
      these aspects. In addition, trials evaluating the long-term effects of anti
      tuberculosis chemoprophylaxis and the influence of level of immunocompromise on
      effectiveness are needed.

PMID- 14973948
TI  - Interventions to help external cephalic version for breech presentation at term.
AB  - BACKGROUND: Breech presentation places a fetus at increased risk. The outcome for
      the baby is improved by planned caesarean section compared with planned vaginal
      delivery. External cephalic version attempts to reduce the chances of breech
      presentation at birth, but is not always successful. Tocolytic drugs to relax the
      uterus as well as other methods have been used in an attempt to facilitate
      external cephalic version at term. OBJECTIVES: To assess the effects of routine
      tocolysis, fetal acoustic stimulation, epidural or spinal analgesia and
      transabdominal amnioinfusion for external cephalic version at term on successful
      version and measures of pregnancy outcome. SEARCH STRATEGY: The Cochrane
      Pregnancy and Childbirth Group trials register (September 2003) and the Cochrane
      Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2003) were
      searched. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing
      routine versus selective or no tocolysis; fetal acoustic stimulation in midline
      fetal spine positions versus dummy or no stimulation; epidural or spinal
      analgesia versus no regional analgesia; or transabdominal amnioinfusion versus no
      amnioinfusion for external cephalic version at term. DATA COLLECTION AND
      ANALYSIS: The reviewer assessed eligibility and trial quality. MAIN RESULTS: In
      six trials, routine tocolysis with beta-stimulants was associated with fewer
      failures of external cephalic version (relative risk (RR) 0.74, 95% confidence
      interval (CI) 0.64 to 0.87). The reduction in non-cephalic presentations at birth
      was not statistically significant. Caesarean sections were reduced (RR 0.85, 95%
      CI 0.72 to 0.99). In four small trials, sublingual nitroglycerine used as a
      tocolytic was associated with significant side-effects, and was not found to be
      effective. Fetal acoustic stimulation in midline fetal spine positions was
      associated with fewer failures of external cephalic version at term (RR 0.17, 95%
      CI 0.05 to 0.60). With epidural or spinal analgesia, external cephalic version
      failure, non-cephalic births and caesarean sections were reduced in two trials
      but not the other. The overall differences were not statistically significant. No
      randomised trials of transabdominal amnioinfusion for external cephalic version
      at term were located. REVIEWER'S CONCLUSIONS: Routine tocolysis appears to reduce
      the failure rate of external cephalic version at term. There is not enough
      evidence to evaluate the use of fetal acoustic stimulation in midline fetal spine
      positions, nor of epidural or spinal analgesia. Large volume intravenous
      preloading may have contributed to the effectiveness demonstrated in two of the
      latter trials.

PMID- 14973949
TI  - Prophylactic ergometrine-oxytocin versus oxytocin for the third stage of labour.
AB  - BACKGROUND: The routine prophylactic administration of an uterotonic agent is an
      integral part of active management of the third stage of labour, helping to
      prevent postpartum haemorrhage (PPH). The two most widely used uterotonic agents
      are: ergometrine-oxytocin (Syntometrine) (a combination of oxytocin 5
      international units (iu) and ergometrine 0.5 mg) and oxytocin (Syntocinon).
      OBJECTIVES: To compare the effects of ergometrine-oxytocin with oxytocin in
      reducing the risk of PPH (blood loss of at least 500 ml) and other maternal and
      neonatal outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group trials register (May 2003). SELECTION CRITERIA: Randomised
      trials comparing ergometrine-oxytocin use with oxytocin use in women having the
      third stage of labour managed actively. DATA COLLECTION AND ANALYSIS: We
      independently assessed trial eligibility and quality and extracted data. We
      contacted study authors for additional information. MAIN RESULTS: Six trials were
      included (9332 women). Compared with oxytocin, ergometrine-oxytocin was
      associated with a small reduction in the risk of PPH using the definition of PPH
      of blood loss of at least 500 ml (odds ratio 0.82, 95% confidence interval 0.71
      to 0.95). This advantage was found for both a dose of 5 iu oxytocin and a dose of
      10 iu oxytocin, but was greater for the lower dose. There was no difference
      detected between the groups using either 5 or 10 iu for the stricter definition
      of PPH of blood loss at least 1000 ml. Adverse effects of vomiting, nausea and
      hypertension were more likely to be associated with the use of ergometrine
      oxytocin. When heterogeneity between trials was taken into account there were no
      statistically significant differences found for the other maternal or neonatal
      outcomes. REVIEWER'S CONCLUSIONS: The use of ergometrine-oxytocin as part of the
      routine active management of the third stage of labour appears to be associated
      with a small but statistically significant reduction in the risk of PPH when
      compared to oxytocin for blood loss of 500 ml or more. No statistically
      significant difference was observed between the groups for blood loss of 1000 ml
      or more. A statistically significant difference was observed in the presence of
      maternal side-effects, including elevation of diastolic blood pressure, vomiting
      and nausea, associated with ergometrine-oxytocin use compared to oxytocin use.
      Thus, the advantage of a reduction in the risk of PPH, between 500 and 1000 ml
      blood loss, needs to be weighed against the adverse side-effects associated with
      the use of ergometrine-oxytocin.

PMID- 14973950
TI  - Calcium channel blockers for neuroleptic-induced tardive dyskinesia.
AB  - BACKGROUND: Tardive dyskinesia is a disfiguring movement disorder of the
      orofacial region often caused by antipsychotic drugs. A wide range of strategies
      has been used to help manage tardive dyskinesia and, for people who are unable to
      have their antipsychotic medication stopped or substantially changed, the calcium
      channel blocking group of drugs (diltiazem, nifedipine, nimodipine, verapamil)
      has been suggested as a useful adjunctive treatment. OBJECTIVES: To determine the
      effects of calcium-channel blocker drugs (diltiazem, nifedipine, nimodipine,
      verapamil) for treatment of neuroleptic-induced tardive dyskinesia in people with
      schizophrenia, schizoaffective disorder or other chronic mental illnesses. SEARCH
      STRATEGY: We updated previous searches of the Cochrane Schizophrenia Group
      Register (1982-2000), Cochrane Library (Issue 4, 2000), Cochrane Schizophrenia
      Group's register of trials (November 2000), EMBASE (1980-2000), LILACS (1982
      2000), MEDLINE (1966-2000), PsycLIT (1974-2000), and SCISEARCH by searching the
      Cochrane Schizophrenia Group Register (September 2003). We searched references of
      all identified studies for further trial citations and contacted authors of
      trials. SELECTION CRITERIA: Randomised clinical trials comparing calcium-channel
      blockers to placebo or no intervention for people with both tardive dyskinesia
      and schizophrenia or serious mental illness. DATA COLLECTION AND ANALYSIS: Data
      were to have been independently extracted and analysed on an intention-to-treat
      basis. The relative risk (RR) and 95% confidence intervals (CI) of homogeneous
      dichotomous data were to have been calculated using a random effects model, and,
      where possible, the number needed to treat calculated. Weighted mean differences
      (WMD) were to have been calculated for continuous data. MAIN RESULTS: No trials
      were included. We excluded fourteen studies; eight were not randomised, one did
      not use calcium channel blockers and five small, randomised, studies reported no
      usable data. REVIEWER'S CONCLUSIONS: The effects of calcium-channel blockers for
      antipsychotic induced tardive dyskinesia are unknown. Their use is experimental
      and should only be given in the context of well designed randomised studies.

PMID- 14973951
TI  - Antibiotics for acute otitis media in children.
AB  - BACKGROUND: Acute otitis media is one of the most common diseases in early
      infancy and childhood. Antibiotic use for acute otitis media varies from 31% in
      the Netherlands to 98% in the USA and Australia. OBJECTIVES: The objective of
      this review was to assess the effects of antibiotics for children with acute
      otitis media. SEARCH STRATEGY: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL); MEDLINE, Index Medicus (pre 1965), Current Contents
      and reference lists of articles from 1958 to January 2000. The search was updated
      in 2003. SELECTION CRITERIA: Randomised trials comparing antimicrobial drugs with
      placebo in children with acute otitis media. DATA COLLECTION AND ANALYSIS: Three
      reviewers independently assessed trial quality and extracted data. MAIN RESULTS:
      Ten trials were eligible based on design, only eight of the trials, with a total
      of 2,287 children, included patient-relevant outcomes. The methodological quality
      of the included trials was generally high. All trials were from developed
      countries. The trials showed no reduction in pain at 24 hours, but a 30% relative
      reduction (95% confidence interval 19% to 40%) in pain at two to seven days.
      Since approximately 80% of patients will have settled spontaneously in this time,
      this means an absolute reduction of 7% or that about 15 children must be treated
      with antibiotics to prevent one child having some pain after two days. There was
      no effect of antibiotics on hearing problems of acute otitis media, as measured
      by subsequent tympanometry. However, audiometry was done in only two studies and
      incompletely reported. Nor did antibiotics influence other complications or
      recurrence. There were few serious complications seen in these trials: only one
      case of mastoiditis occurred in a penicillin treated group. REVIEWER'S
      CONCLUSIONS: Antibiotics provide a small benefit for acute otitis media in
      children. As most cases will resolve spontaneously, this benefit must be weighed
      against the possible adverse reactions. Antibiotic treatment may play an
      important role in reducing the risk of mastoiditis in populations where it is
      more common.

PMID- 14973953
TI  - Multicomponent fortified human milk for promoting growth in preterm infants.
AB  - BACKGROUND: For term infants, human milk provides adequate nutrition to
      facilitate growth, as well as potential beneficial effects on immunity and the
      maternal-infant emotional state. However, the role of human milk in premature
      infants is less well defined as it contains insufficient quantities of some
      nutrients to meet the estimated needs of the infant. Observational studies have
      suggested that infants fed formula have a higher rate of growth than infants who
      are breast fed. However, there are potential short term and long term benefits
      from human milk. Commercially-produced multicomponent fortifiers provide
      additional nutrients to supplement human milk (in the form of protein, calcium,
      phosphate, and carbohydrate, as well as vitamins and trace minerals). OBJECTIVES:
      The main objective was to determine if addition of multicomponent nutritional
      supplements to human milk leads to improved growth, bone metabolism and
      neurodevelopmental outcomes without significant adverse effects in premature
      infants. SEARCH STRATEGY: Searches were made of the Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 3003), MEDLINE
      (searched August 29, 2003), previous reviews including cross references,
      abstracts, conferences and symposia proceedings, expert informants, journal
      handsearching mainly in the English language. SELECTION CRITERIA: All trials
      utilising random or quasi-random allocation to supplementation of human milk with
      multiple nutrients or no supplementation in premature infants within a nursery
      setting were eligible. DATA COLLECTION AND ANALYSIS: Data were extracted using
      the standard methods of the Cochrane Collaboration and its Neonatal Review Group,
      with separate evaluation of trial quality and data extraction by each author and
      synthesis of data using relative risk and weighted mean difference. MAIN RESULTS:
      Supplementation of human milk with multicomponent fortifiers is associated with
      short term increases in weight gain, linear and head growth. There is no effect
      on serum alkaline phosphatase levels; it is not clear if there is an effect on
      bone mineral content. Nitrogen retention and blood urea levels appear to be
      increased. There are insufficient data to evaluate long term neurodevelopmental
      and growth outcomes, although there appears to be no effect on growth beyond one
      year of life. Use of multicomponent fortifiers does not appear to be associated
      with adverse effects, although the total number of infants studied and the large
      amount of missing data reduces confidence in this conclusion. Blood urea levels
      are increased and blood pH levels minimally decreased, but the clinical
      significance of this is uncertain. REVIEWER'S CONCLUSIONS: Multicomponent
      fortification of human milk is associated with short-term improvements in weight
      gain, linear and head growth. Despite the absence of evidence of long-term
      benefit and insufficient evidence to be reassured that there are no deleterious
      effects, it is unlikely that further studies evaluating fortification of human
      milk versus no supplementation will be performed. Further research should be
      directed toward comparisons between different proprietary preparations and
      evaluating both short-term and long-term outcomes in search of the "optimal"
      composition of fortifiers.

PMID- 14973952
TI  - Discharge planning from hospital to home.
AB  - BACKGROUND: Discharge planning is a routine feature of health systems in many
      countries. The aim is to reduce hospital length of stay and unplanned readmission
      to hospital, and improve the co ordination of services following discharge from
      hospital thereby bridging the gap between hospital and place of discharge.
      Sometimes discharge planning is offered as part of an integrated package of care,
      which may cover both the hospital and community. The focus of this review is
      discharge planning that occurs while a patient is in hospital; we exclude studies
      that evaluate discharge planning with follow up care. OBJECTIVES: To determine
      the effectiveness of planning the discharge of patients moving from hospital.
      SEARCH STRATEGY: Relevant studies were identified using Medline, Embase, SIGLE
      database for grey literature, Bioethics database, Health Plan, Psych. Lit,
      Sociofile, CINAHL, Cochrane Library, Econ Lit, Social Science Citation Index,
      EPOC register. The review was updated using the EPOC trials register in August
      2002. SELECTION CRITERIA:  STUDY DESIGN: randomised controlled trials (RCTs) that
      compare discharge planning (the development of an individualised discharge plan)
      with routine discharge care. PARTICIPANTS: all patients in hospital.
      INTERVENTION: the development of an individualised discharge plan. DATA
      COLLECTION AND ANALYSIS: Data analysis and quality assessment was undertaken
      independently by two reviewers using a data checklist. Studies are grouped
      according to patient group (elderly medical patients, surgical patients, and
      those with a mix of conditions), and by outcome. MAIN RESULTS: Three new studies
      were included in this update. In total we included eleven RCTS: 6 trials
      recruited patients with a medical condition (2,368 patients), and four recruited
      patients with a mix of medical and surgical conditions (2,983 patients), one of
      these four recruited medical and surgical patients as separate groups, and the
      final trial recruited 97 patients in a psychiatric hospital and from a general
      hospital. We failed to detect a difference between groups in mortality for
      elderly patients with a medical condition (OR 1.44 95% CI 0.82 to 2.51), hospital
      length of stay (weighted mean difference -0.86, 95% CI -1.9 to 0.18), readmission
      rates (OR 0.91 95% CI 0.67 to 1.23) and being discharged from hospital to home
      (OR 1.15 95% CI 0.72 to 1.82). This was also the case for trials recruiting
      patients recovering from surgery and those recruiting patients with a mix of
      medical and surgical conditions. One trial comparing a structured care pathway
      for patients recovering from a stroke with multidisciplinary care reported a
      significant rate of improvement in functional ability and quality of life for the
      control group (median change in Barthel score between 4 to 12 weeks of 2 points
      for the treatment group, versus 6 for the control group, p<0.01); (Euroqol scores
      at 6 months 63 for the treatment group, vs. 72 for the control group, p<0.005).
      Two trials reported that patients with medical conditions allocated to discharge
      planning reported increased satisfaction compared with those who received routine
      discharge. No statistically significant differences were reported for overall
      health care costs. REVIEWER'S CONCLUSIONS: The impact of discharge planning on
      readmission rates, hospital length of stay, health outcomes and cost is
      uncertain. This reflects a lack of power as the degree to which we could pool
      data was restricted by the different reported measures of outcome. It is possible
      that even a small reduction in length of stay, or readmission rate, could have an
      impact on the timeliness of subsequent admissions in a system where there is an
      shortage of acute hospital beds.

PMID- 14973954
TI  - Homeopathy for chronic asthma.
AB  - BACKGROUND: Homeopathy involves the use, in dilution, of substances which cause
      symptoms in their undiluted form. It is one of the most widespread forms of
      complementary medicines and is also used to treat asthma. OBJECTIVES: The
      objective of this review was to assess the effects of homeopathy in people with
      chronic stable asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group
      trials register, the Cochrane Complementary Medicine Field trials register, the
      Glasgow Homeopathic Hospital database, the Munchener Modell database and
      reference lists of articles. Searches were current as of August 2003. SELECTION
      CRITERIA: Randomised trials of homeopathy for the treatment of stable chronic
      asthma, with observation periods of at least one week were included. DATA
      COLLECTION AND ANALYSIS: Data extraction was undertaken by two reviewers. Trial
      quality was assessed by the reviewers. MAIN RESULTS: Six trials with a total of
      556 people were included. These trials were all placebo-controlled and double
      blind, but of variable quality. They used different homeopathic treatments which
      precluded quantitative pooling of results for the primary outcome. Standardised
      treatments in these trials are unlikely to represent common homeopathic practice,
      where treatment tends to be individualised. No trial reported a significant
      difference on validated symptom scales. There were conflicting results in terms
      of lung function between the studies. There has been only a limited attempt to
      measure a 'package of care' effect (i.e., the effect of the medication as well as
      the consultation, which is considered a vital part of individualised homeopathic
      practice). REVIEWER'S CONCLUSIONS: There is not enough evidence to reliably
      assess the possible role of homeopathy in asthma. As well as randomised trials,
      there is a need for observational data to document the different methods of
      homeopathic prescribing and how patients respond. This will help to establish to
      what extent people respond to a 'package of care' rather than the homeopathic
      intervention alone.

PMID- 14973955
TI  - Intravenous immunoglobulin for preventing infection in preterm and/or low-birth
      weight infants.
AB  - BACKGROUND: Nosocomial infections continue to be a significant cause of morbidity
      and mortality among preterm and/or low birth weight infants. Maternal transport
      of immunoglobulins to the fetus mainly occurs after 32 weeks gestation and
      endogenous synthesis does not begin until several months after birth.
      Administration of intravenous immunoglobulin provides IgG that can bind to cell
      surface receptors, provide opsonic activity, activate complement, promote
      antibody dependent cytotoxicity, and improve neutrophilic chemo luminescence.
      Intravenous immunoglobulin thus has the potential of preventing or altering the
      course of nosocomial infections. OBJECTIVES: To assess the effectiveness/safety
      of intravenous immunoglobulin (IVIG) administration (compared to placebo or no
      intervention) to preterm (< 37 weeks gestational age at birth) and/or low birth
      weight (LBW) (< 2500 g BW) infants in preventing nosocomial infections. SEARCH
      STRATEGY: MEDLINE, EMBASE, and The Cochrane Library Databases were searched in
      September 2003 using the keywords: immunoglobulin and infant-newborn and random
      allocation or controlled trial or randomized controlled trial (RCT). The
      reference lists of identified RCTs and personal files were searched. No language
      restrictions were applied. SELECTION CRITERIA: The criteria used to select
      studies for inclusion in this overview were: 1) DESIGN: RCTs in which
      administration of IVIG was compared to a control group that received a placebo or
      no intervention. 2) POPULATION: preterm (< 37 weeks gestational age) and/or LBW
      (<2500 g) infants. 3) INTERVENTION: IVIG for the prevention of bacterial/fungal
      infection during initial hospital stay (8 days or longer). (Studies that were
      primarily designed to assess the effect of IVIG on humoral immune markers were
      excluded as were studies in which the follow-up period was one week or less).4)
      At least one of the following outcomes was reported: sepsis, any serious
      infection, death from all causes, death from infection, length of hospital stay,
      intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC),
      bronchopulmonary dysplasia (BPD). DATA COLLECTION AND ANALYSIS: Two reviewers
      independently abstracted information for each outcome reported in each study, and
      one researcher (AO) checked for any discrepancies and pooled the results.
      Relative risk (RR) and Risk Difference (RD) with 95% confidence intervals (CI)
      using the fixed effects model are reported. When a statistically significant RD
      was found the number needed to treat (NNT) was also calculated with 95% CIs. The
      results include all accepted studies in which the outcome of interest was
      reported. Statistically significant between study heterogeneity was reported. The
      results of the inconsistency test (I squared) are also reported when
      statistically significant heterogeneity was found. MAIN RESULTS: No new trials
      were identified in September 2003. Nineteen studies met inclusion criteria. These
      included approximately 5,000 preterm and/or LBW infants and reported on at least
      one of the outcomes of interest for this systematic review. When all studies were
      combined there was a statistically significant reduction (p = 0.02) in sepsis, RR
      [0.85 (95% CI 0.74, 0.98)] and RD [-0.03 (95% CI 0.00, -0.05)], NNT 33. There was
      statistically significant between-study heterogeneity (p = 0.02); I squared 54%.
      A statistically significant reduction was found for any serious infection, one or
      more episodes, when all studies were combined [RR 0.82 (95% CI 0.74, 0.92); RD 
      0.04 (95% CI -0.02, -0.06,); NNT 25 (95% CI, 16.7, 50). There was statistically
      significant between-study heterogeneity (p = 0.0006); I squared 50%. There were
      no statistically significant differences for mortality from all causes, mortality
      from infection, incidence of NEC, BPD and IVH or length of hospital stay. No
      major adverse effects of IVIG were reported in any of the studies. REVIEWER'S
      CONCLUSIONS: IVIG administration results in a 3% reduction in sepsis and a 4%
      reduction in any serious infection, one or more episodes, but is not associated
      with reductions in other important outcomes: sepsis, NEC, IVH, or length of
      hospital stay. Most importantly, IVIG administration does not have any
      significant effect on mortality from any cause or from infections. Prophylactic
      use of IVIG is not associated with any short term serious side effects. From a
      clinical perspective a 3-4% reduction in nosocomial infections without a
      reduction in mortality or other important clinical outcomes is of marginal
      importance.The decision to use prophylactic IVIG will depend on the costs and the
      values assigned to the clinical outcomes. There is no justification for further
      RCTs testing the efficacy of previously studied IVIG preparations to reduce
      nosocomial infections in preterm and/or LBW infants. The results of these meta
      analyses should encourage basic scientists and clinicians to pursue other avenues
      to prevent nosocomial infections.

PMID- 14973956
TI  - Longchain polyunsaturated fatty acid supplementation in preterm infants.
AB  - BACKGROUND: The n-3 and n-6 essential fatty acids alpha linolenic acid (ALA) and
      linoleic acid (LA) are the precursors of the n-3 and n-6 longchain
      polyunsaturated fatty acids (LCPUFA). Controversy exists over whether LCPUFA are
      essential nutrients for preterm infants who may not be able to synthesise
      sufficient amounts of LCPUFA to satisfy the needs of the developing brain and
      retina. OBJECTIVES: The aim of this review is to assess whether supplementation
      of formula with LCPUFA is safe and of benefit to preterm infants. SEARCH
      STRATEGY: Trials were identified by MEDLINE (October 2003), Oxford Database of
      Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library, Issue 2, 2003) and by checking reference lists of relevant
      articles and conference proceedings. SELECTION CRITERIA: All randomised trials of
      formula supplemented with LCPUFA and with clinical endpoints were reviewed. DATA
      COLLECTION AND ANALYSIS: Eleven randomised trials assessing the clinical effects
      of feeding formula supplemented with LCPUFA were included in the review. MAIN
      RESULTS: Of the eleven randomised trials included in the review, two of these
      were not classified as of high quality despite blinded assessment and complete
      follow-up, due to problems with assessment methodology. VISUAL ACUITY: Visual
      acuity over the first year was measured by Teller acuity cards in six studies, by
      VEP in four studies and by ERG in two studies. Most studies found no significant
      differences in any visual assessment between supplemented and control infants.
      DEVELOPMENT: Most of the trials have used Bayley Scales of Infant Development
      (BSID) at 12 to 24 months postterm and shown no significant effect following
      supplementation. Meta-analysis of BSID of three studies (Fewtrell 2002, O'Connor
      2001, van Wezel 2002) shows no significant effect of supplementation on
      development. Carlson 1993 and Carlson 1996 demonstrated lower novelty preferences
      (possibly predictive of lower intelligence) in the supplemented compared with the
      control group. The investigators however concluded that supplemented infants may
      have more rapid visual information processing given that they had more looks and
      each look was of shorter duration. GROWTH: Most trials have reported no
      significant effect of LCPUFA supplementation on growth of preterm infants. Two
      trials (Carlson 1993, Carlson 1996) suggest that LCPUFA supplemented infants grow
      less well than controls, possibly due to a reduction in AA levels which occurs
      when n-3 supplements are used without n-6 supplements. Recent trials with
      addition of AA to the supplement have reported no significant effect on growth.
      Fewtrell 2002 reported mild reductions in length and weight z scores at 18
      months. Contrary to these results, the meta-analysis of five studies (Uauy 1992,
      Carlson 1996, Hansen 1997, Vanderhoof 1999, Innis 2002) showed increased weight
      and length at two months post-term in supplemented infants. SIDE EFFECTS: Uauy
      1992 reported no significant effect of LCPUFA supplementation on bleeding time
      and red cell membrane fragility. REVIEWER'S CONCLUSIONS: Infants enrolled in the
      trials were relatively mature and healthy preterm infants. Assessment schedule
      and methodology, dose and source of supplementation and fatty acid composition of
      the control formula varied between trials. No long-term benefits were
      demonstrated for infants receiving formula supplemented with LCPUFA. There was no
      evidence that supplementation of formula with n-3 and n-6 LCPUFA impaired the
      growth of preterm infants.

PMID- 14973957
TI  - Pulsatile gonadotrophin releasing hormone for ovulation induction in subfertility
      associated with polycystic ovary syndrome.
AB  - BACKGROUND: In normal menstrual cycles, gonadotrophin releasing hormone (GnRH)
      secretion is pulsatile, with intervals of 60-120 minutes in the follicular phase.
      Treatment with pulsatile GnRH infusion by the intravenous or subcutaneous route
      using a portable pump has been used successfully in patients with
      hypogonadotrophic hypogonadism. Assuming that the results would be similar in
      women with polycystic ovary syndrome (PCOS), pulsatile GnRH has been used to
      induce ovulation in these women. Although ovulation and pregnancy have been
      achieved, the effectiveness of pulsatile GnRH in women with PCOS has not been
      clearly demonstrated. OBJECTIVES: To assess the effectiveness of pulsatile GnRH
      administration in women with polycystic ovary syndrome (PCOS), in terms of
      ongoing pregnancy, ovulation, clinical pregnancy, ovarian hyperstimulation
      syndrome (OHSS), multiple pregnancy, miscarriage, and multifollicular growth.
      SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders & Subfertility
      Group trials register (searched 13 August 2003), the Cochrane Central Register of
      Controlled Trials (CENTRAL) (Cochrane Library Issue 2, August 2001), MEDLINE
      (January 1966 to August 2003), EMBASE (January 1985 to August 2003) and reference
      lists of articles. We also contacted manufacturers and researchers in the field.
      SELECTION CRITERIA: All relevant published randomised clinical trials were
      selected for inclusion if treatment consisted of pulsatile GnRH administration
      versus another treatment for ovulation induction in subfertile women with PCOS.
      DATA COLLECTION AND ANALYSIS: Relevant data were extracted independently by two
      reviewers (NB, MW). Validity was assessed in terms of method of randomisation,
      completeness of follow-up, presence or absence of crossover and co-intervention.
      All trials were screened and analysed for predetermined quality criteria. DATA
      SYNTHESIS: 2X2 tables were generated for all the relevant outcomes. Odds ratios
      were generated using the Peto method. MAIN RESULTS: Four randomised clinical
      trials involving 57 women were identified comparing four different treatments:
      GnRH versus HMG, GnRH and FSH versus FSH, GnRH following pretreatment with GnRH
      agonist (GnRHa) versus GnRH only, GnRH following pretreatment with GnRHa versus
      clomiphene citrate. This means that there was only one trial in any one
      comparison. In two studies, data of pre- and post-crossover were not described
      separately. All trials were small and of too short duration to show any
      significant differences in pregnancy results. The odds ratio for ongoing
      pregnancy, only described in one trial, was 7.5 (95% CI 0.44 to 127) in the
      comparison GnRH following pretreatment with GnRHa versus GnRH only in favour of
      the first group. Multiple pregnancies were not seen. Ovarian hyperstimulation
      syndrome was seen only in women allocated to ovulation induction with HMG.
      REVIEWER'S CONCLUSIONS: The four trials describing four different comparisons
      with a short follow up (1 to 3 cycles) were too small to either prove or discard
      the value of pulsatile GnRH treatment in patients with polycystic ovary syndrome.

PMID- 14973958
TI  - Spinal manipulative therapy for low back pain.
AB  - BACKGROUND: Low-back pain is a costly illness for which spinal manipulative
      therapy is commonly recommended. Previous systematic reviews and practice
      guidelines have reached discordant results on the effectiveness of this therapy
      for low-back pain. OBJECTIVES: To resolve the discrepancies related to the use of
      spinal manipulative therapy and to update previous estimates of effectiveness, by
      comparing spinal manipulative therapy with other therapies and then incorporating
      data from recent high-quality randomized, controlled trials (RCTs) into the
      analysis. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials,
      MEDLINE, EMBASE and CINAHL were electronically searched from their respective
      beginning to January 2000, using the Back Group search strategy; references from
      previous systematic reviews were also screened. SELECTION CRITERIA: Randomized,
      controlled trials (RCT) that evaluated spinal manipulative therapy for patients
      with low-back pain, with at least one day of follow-up, and at least one
      clinically-relevant outcome measure. DATA COLLECTION AND ANALYSIS: Two authors,
      who served as the reviewers for all stages of the meta-analysis, independently
      extracted data from unmasked articles. Comparison treatments were classified into
      the following seven categories: sham, conventional general practitioner care,
      analgesics, physical therapy, exercises, back school, or a collection of
      therapies judged to be ineffective or even harmful (traction, corset, bed rest,
      home care, topical gel, no treatment, diathermy, and minimal massage). MAIN
      RESULTS: Thirty-nine RCTs were identified. Meta-regression models were developed
      for acute or chronic pain and short-term and long-term pain and function. For
      patients with acute low-back pain, spinal manipulative therapy was superior only
      to sham therapy (10-mm difference [95% CI, 2 to 17 mm] on a 100-mm visual
      analogue scale) or therapies judged to be ineffective or even harmful. Spinal
      manipulative therapy had no statistically or clinically significant advantage
      over general practitioner care, analgesics, physical therapy, exercises, or back
      school. Results for patients with chronic low-back pain were similar. Radiation
      of pain, study quality, profession of manipulator, and use of manipulation alone
      or in combination with other therapies did not affect these results. REVIEWER'S
      CONCLUSIONS: There is no evidence that spinal manipulative therapy is superior to
      other standard treatments for patients with acute or chronic low-back pain.

PMID- 14973959
TI  - Prostaglandins for prevention of postpartum haemorrhage.
AB  - BACKGROUND: Prostaglandins have mainly been used for postpartum haemorrhage when
      other measures fail. Misoprostol, a new and inexpensive prostaglandin E1
      analogue, has been suggested as an alternative for routine management of the
      third stage of labour. OBJECTIVES: To assess the effects of prophylactic
      prostaglandin use in the third stage of labour. SEARCH STRATEGY: The Cochrane
      Pregnancy and Childbirth Group trials register (March 2003). SELECTION CRITERIA:
      Randomized or quasi-randomized trials comparing a prostaglandin agent with
      another uterotonic or no prophylactic uterotonic (nothing or placebo) as part of
      management of the third stage of labour. There were no language preferences. DATA
      COLLECTION AND ANALYSIS: Eligibility, trial quality and data extraction were done
      by two reviewers independently. MAIN RESULTS: Twenty-four misoprostol and eight
      intramuscular prostaglandin trials (34,203 participants) were included. The data
      comparing oral misoprostol to no uterotonics/placebo are from five trials and
      difficult to interpret because of the heterogeneity between trials. However, the
      data do not suggest a substantive reduction in the rate of postpartum haemorrhage
      or other measures of blood loss. Oral misoprostol 600 mcg shows clinically and
      statistically significantly more blood loss = 1000 ml compared with conventional
      injectable uterotonics (seven trials, 22,749 women, 3.6% versus 2.7%; relative
      risk (RR) 1.34, 95% confidence interval (CI) 1.16 to 1.55). Shivering and
      elevated body temperature (> 38 masculine C) are the main side-effects of
      misoprostol and are dose related (600 mcg versus 400 mcg: shivering - two trials,
      RR: 1.33; 95% CI: 1.07 to 1.64). Compared to oxytocin the RR of any shivering
      with 600 mcg oral misoprostol is 3.29 (seven trials, 22746 women; 19.7% versus
      6.0%, 95% CI 3.03 to 3.56) and temperature greater than 38 masculine C is RR 6.78
      (seven trials, 22,09 women; 6.3% versus, 95% CI 5.55 to 8.30). Injectable
      prostaglandins are associated with reduced mean blood loss in the third stage of
      labour (weighted mean difference -70 ml, 95% CI -73 to -67 ml) when compared to
      conventional injectable uterotonics but have more side-effects. There are scarce
      data from this comparison on severe postpartum haemorrhage and the use of
      additional uterotonics, the primary outcomes of this review. REVIEWER'S
      CONCLUSIONS: Neither intramuscular prostaglandins nor misoprostol are preferable
      to conventional injectable uterotonics as part of the active management of the
      third stage of labour especially for low-risk women. Future research on
      prostaglandin use after birth should focus on the treatment of postpartum
      haemorrhage rather than prevention where they seem to be more promising.

PMID- 14973960
TI  - Interventions for treating hallux valgus (abductovalgus) and bunions.
AB  - BACKGROUND: Hallux valgus is classified as an abnormal deviation of the great toe
      (hallux) towards the midline of the foot. OBJECTIVES: To identify and evaluate
      the evidence from randomised trials of interventions used to correct hallux
      valgus. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group
      trials register (2003/1), the Cochrane Central Register of Controlled Trials (The
      Cochrane Library issue 1, 2003), MEDLINE (January 1966 to March 2003) and EMBASE
      (1980 to January 2003). No language restrictions were applied. Hand searching of
      specific foot journals was also undertaken. Date of the most recent search: 31st
      March 2003. SELECTION CRITERIA: Randomised or quasi-randomised trials of both
      conservative and surgical treatments of hallux valgus. Excluded were studies
      comparing areas of surgery not specific to the control of the deformity such as
      use of anaesthetics or tourniquet placement. DATA COLLECTION AND ANALYSIS:
      Methodological quality of trials which met the inclusion criteria was
      independently assessed by two reviewers. Data extraction was undertaken by two
      reviewers. The trials were grouped according to the interventions being compared,
      but the dissimilarity in the comparisons prevented pooling of results. MAIN
      RESULTS: The methodological quality of the 21 included trials was generally poor
      and trial sizes were small. Three trials involving 332 participants evaluated
      conservative treatments versus no treatment. There was no evidence of a
      difference in outcomes between treatment and no treatment. One good quality trial
      involving 140 participants compared surgery to conservative treatment. Evidence
      was shown of an improvement in all outcomes in patients receiving chevron
      osteotomy compared with those receiving orthoses. The same trial also compared
      surgery to no treatment in 140 participants. Evidence was shown of an improvement
      in all outcomes in patients receiving chevron osteotomy compared with those
      receiving no treatment. Two trials involving 133 people with hallux valgus
      compared Keller's arthroplasty with other surgical techniques. In general, there
      was no advantage or disadvantage using Keller's over the other techniques. When
      the distal osteotomy was compared to Keller's arthroplasty, the osteotomy showed
      evidence of improving the intermetatarsal angle and preserving joint range of
      motion. The arthroplasty was found to have less of an impact on walking ability
      compared to the arthrodesis. Six trials involving 309 participants compared
      chevron (and chevron-type) osteotomy with other techniques. The chevron osteotomy
      offered no advantages in these trials. For some outcomes, other techniques gave
      better results. Two of these trials (94 participants) compared a type of proximal
      osteotomy to a proximal chevron osteotomy and found no evidence of a difference
      in outcomes between techniques. Three trials involving 157 participants compared
      outcomes between original operations and surgeon's adaptations. There was no
      advantage found for any of the adaptations. Three trials involving 71 people with
      hallux valgus compared new methods of fixation to traditional methods. There was
      no evidence that the new methods of fixation were detrimental to the outcome of
      the patients. Four trials involving 162 participants evaluated methods of post
      operative rehabilitation. The use of continuous passive motion appeared to give
      an improved range of motion and earlier recovery following surgery. Early
      weightbearing or the use of a crepe bandage were not found to be detrimental to
      final outcome. REVIEWER'S CONCLUSIONS: Only a few studies had considered
      conservative treatments. The evidence from these suggested that orthoses and
      night splints did not appear to be any more beneficial in improving outcomes than
      no treatment. Surgery (chevron osteotomy) was shown to be beneficial compared to
      orthoses or no treatment, but when compared to other osteotomies, no technique
      was shown to be superior to any other. Only one trial had compared an osteotomy
      to an arthroplasty. There was limited evidence to suggest that the osteotomy gat
      the osteotomy gave the better outcomes. It was notable that the numbers of
      participants in some trials remaining dissatisfied at follow-up were consistently
      high (25 to 33%), even when the hallux valgus angle and pain had improved. A few
      of the more recent trials used assessment scores that combine several aspects of
      the patients outcomes. These scoring systems are useful to the clinician when
      comparing techniques but are of dubious relevance to the patient if they do not
      address their main concern and such scoring systems are frequently unvalidated.
      Only one study simply asked the patient if they were better than before the
      treatment. Final outcomes were most frequently measured at one year, with a few
      trials maintaining follow-up for 3 years. Such time-scales are minimal given that
      the patients will be on their feet for at least another 20-30 years after
      treatment. Future research should include patient-focused outcomes, standardised
      assessment criteria and longer surveillance periods, more usefully in the region
      of 5-10 years.

PMID- 14973961
TI  - Infusion techniques for peripheral arterial thrombolysis.
AB  - BACKGROUND: Thrombolytic therapy is a useful tool in the management of acute
      peripheral arterial ischaemia. Fibrinolytic drugs are used to disperse blood clot
      to clear arterial occlusion. A variety of techniques are used to deliver these
      agents. OBJECTIVES: To determine the optimal technique for infusion of
      fibrinolytic drugs in peripheral arterial ischaemia. SEARCH STRATEGY: The
      Cochrane Library (issue 3, 2003) and the Specialised Trials Register of the
      Cochrane Review Group on Peripheral Vascular Diseases (July 2003) were searched.
      Proceedings from meetings of British, European and North American Vascular
      Surgical and Radiological Societies, plus reference lists of identified studies
      were also searched for relevant trials. Major pharmaceutical firms and trialists
      were asked about unpublished trials. SELECTION CRITERIA: Two reviewers
      independently selected randomised controlled trials comparing infusion techniques
      of fibrinolytic agents in the treatment of acute peripheral arterial ischaemia.
      Trials with poor quality methodology were excluded. DATA COLLECTION AND ANALYSIS:
      Data from included trials were collated and analysed for the following outcomes:
      limb salvage, amputation, death, vessel patency, time to achieve thrombolysis,
      and reduction in the need for surgical intervention. Complication rates were
      compared for: major haemorrhage, cerebrovascular accident and distal
      embolization. MAIN RESULTS: Intra-arterial delivery of thrombolytic agents
      appeared to be more effective than intravenous administration. Thrombolysis was
      more effective when the angiographic catheter was placed within the thrombus.
      Although 'high dose' and 'forced infusion' techniques achieved vessel patency in
      less time than 'low dose infusion', there were more bleeding complications, and
      no increase in patency rates or improvement in limb salvage at 30 days.
      REVIEWER'S CONCLUSIONS: Implications for practice Thrombolysis should be reserved
      for patients with limb threatening ischaemia, due to the high risk of haemorrhage
      or death. Greater benefit is seen when the thrombolytic agent is delivered into
      the thrombus. Systemic intravenous thrombolysis is less effective than intra
      arterial thrombolysis and is associated with an increase in bleeding
      complications. 'High dose' and 'forced infusion' techniques, or adjunctive agents
      such as platelet glycoprotein IIb/IIIa inhibitors may speed up thrombolysis, but
      these are not accompanied by lower amputation rates or a decreased need for
      adjunctive endovascular or surgical procedures. 'Low dose continuous infusion',
      following initial lacing of the thrombus with a high dose of the thrombolytic
      agent, is the least labour intensive technique. Implications for research Only
      large multicentre trials with carefully controlled inclusion criteria will be
      sufficiently powerful to demonstrate genuine benefit for a particular
      thrombolytic regime.

PMID- 14973962
TI  - Prostanoids for intermittent claudication.
AB  - BACKGROUND: Peripheral arterial occlusive disease (PAOD) is a common cause of
      morbidity in the general population. While numerous studies have established the
      efficacy of prostanoids in PAOD stages III and IV the question of the role of
      prostanoids as an alternative or additive treatment in patients suffering from
      claudicatio intermittens (PAOD II) has not yet been clearly answered. OBJECTIVES:
      The aim of this review was to evaluate effects of prostanoids in patients with
      intermittent claudication. SEARCH STRATEGY: Computerised searches of the Cochrane
      Peripheral Vascular Diseases Specialised Register (last searched April 2003), The
      Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue 1,
      2003), MEDLINE and EMBASE were undertaken. In addition relevant journals were
      hand-searched. SELECTION CRITERIA: Randomized clinical trials describing the
      effects of prostanoids in the treatment of patients suffering from intermittent
      claudication have been considered for inclusion. DATA COLLECTION AND ANALYSIS:
      All reviewers assessed the quality of studies and extracted data unblinded.
      Statistical analysis including tests for heterogeneity and overall effect were
      performed by using MetaView of Review Manager 4.2. All numeric values are
      expressed as mean +/- Standard deviation (SD). MAIN RESULTS: Eighteen studies
      were included for analysis. A significant heterogeneity between the included
      studies was detected in most of the subgroup analysis. Five studies compared the
      effects of prostaglandin E1 (PGE1) versus placebo, and reported in their
      individual results significant increases in walking distances after the
      administration of PGE1. The attained increase in walking distances appears to be
      not merely a short-term effect because several studies reported that walking
      capacity remained increased even after termination of treatment. On the other
      hand, oral or intravenous prostacyclin did not increase the walking distances
      significantly. At least one adverse reaction was reported from 23.6% of the
      patients treated with prostacyclin (PGI2), and its analogues and from 13.7% of
      the patients treated with PGE1. REVIEWER'S CONCLUSIONS: Because of the
      heterogeneity between most of the included studies, we did not pool relevant
      parts of the data by meta-analysis. Based on the individual results of the
      published literature, patients with intermittent claudication seem to benefit
      from administration (intravenous or intra-arterial) of PGE1 by a significant
      improvement of their walking capacity. Further well-conducted randomized, double
      blinded trials, with a sufficient number of patients to provide statistical
      powerful information, should be performed to confirm the results of this review.

PMID- 14973963
TI  - Topical ointment for preventing infection in preterm infants.
AB  - BACKGROUND: Nosocomial sepsis is a frequent and serious complication of premature
      infants. The increased susceptibility of ELBW infants to infection has been
      attributed to less effective immune function compared to mature newborns and the
      invasive nature of necessary supportive care. Breakdown of the barrier function
      of the skin may be an additional risk factor for nosocomial sepsis. OBJECTIVES:
      To assess the effect of prophylactic application of topical ointment on
      nosocomial sepsis rates and other complications of prematurity in preterm
      infants. SEARCH STRATEGY: Searches were made of the Cochrane Central Registry of
      Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2003), Ovid DC MEDLINE
      through June 2003, previous reviews including cross references, abstracts,
      conference and symposia proceedings, expert informants, and journal hand
      searching in the English language. SELECTION CRITERIA: Randomized controlled
      trials which compared the effect of prophylactic application of topical ointment
      to routine (standard) skin care or as needed topical therapy in preterm infants
      are included in this review. DATA COLLECTION AND ANALYSIS: Data regarding
      clinical outcomes including infection [including any bacterial infection,
      bacterial infection with a known pathogen, coagulase negative staphylococcal
      infection, fungal infection, and any nosocomial infection (bacterial or fungal)],
      patent ductus arteriosus, oxygen requirement at 28 days, chronic lung disease and
      mortality were excerpted from the reports of the clinical trials by the
      reviewers. Data analysis was done in accordance with the standards of the
      Cochrane Neonatal Review Group. MAIN RESULTS: Four randomized controlled trials
      were identified. All four studies reported improved skin condition in infants
      treated with prophylactic topical ointment (results not reported here). All four
      studies reported on the incidence of any nosocomial infection, fungal infection
      and coagulase negative staphylococcal infection. Infants treated with
      prophylactic topical ointment are at increased risk of coagulase negative
      staphylococcal infection (typical relative risk 1.31, 95% CI 1.02, 1.70; typical
      risk difference 0.04, 95% CI 0.00, 0.08); and any nosocomial infection (typical
      relative risk 1.20, 95% CI 1.00, 1.43; typical risk difference 0.05, 95% CI 0.00,
      0.09). A trend toward increased risk of any bacterial infection was found in
      infants treated with prophylactic topical ointment (typical relative risk 1.19,
      95% CI 0.97, 1.46; typical risk difference 0.04, 95% CI -0.01, 0.08). There was
      no significant difference found in the risk of bacterial infection with a known
      pathogen, fungal infection, or other complications related to prematurity.
      REVIEWER'S CONCLUSIONS: Prophylactic application of topical ointment increases
      the risk of coagulase negative staphylococcal infection and any nosocomial
      infection. A trend toward increased risk of any bacterial infection was noted in
      infants prophylactically treated. Topical ointment should not be used routinely
      in preterm infants.

PMID- 14973964
TI  - Nursing interventions for smoking cessation.
AB  - BACKGROUND: Health care professionals, including nurses, frequently advise
      patients to improve their health by stopping smoking. Such advice may be brief,
      or part of more intensive interventions. OBJECTIVES: To determine the
      effectiveness of nursing-delivered smoking cessation interventions. SEARCH
      STRATEGY: We searched the Cochrane Tobacco Addiction Group specialized register
      and CINAHL in June 2003. SELECTION CRITERIA: Randomized trials of smoking
      cessation interventions delivered by nurses or health visitors with follow-up of
      at least six months. DATA COLLECTION AND ANALYSIS: Two authors extracted data
      independently. MAIN RESULTS: Twenty-nine studies met the inclusion criteria.
      Twenty studies comparing a nursing intervention to a control or to usual care
      found the intervention to significantly increase the odds of quitting (Peto Odds
      Ratio 1.47, 95% CI 1.29 to 1.68). There was heterogeneity among the study
      results, but pooling using a random effects model did not alter the estimate of a
      statistically significant effect. There was limited evidence that interventions
      were more effective for hospital inpatients with cardiovascular disease than for
      inpatients with other conditions. Interventions in non-hospitalized patients also
      showed evidence of benefit. Five studies comparing different nurse-delivered
      interventions failed to detect significant benefit from using additional
      components. Five studies of nurse counselling on smoking cessation during a
      screening health check, or as part of multifactorial secondary prevention in
      general practice (not included in the main meta-analysis) found the nursing
      intervention to have less effect under these conditions. REVIEWER'S CONCLUSIONS:
      The results indicate the potential benefits of smoking cessation advice and/or
      counselling given by nurses to patients, with reasonable evidence that
      interventions can be effective. The challenge will be to incorporate smoking
      behaviour monitoring and smoking cessation interventions as part of standard
      practice, so that all patients are given an opportunity to be asked about their
      tobacco use and to be given advice and/or counselling to quit along with
      reinforcement and follow-up.

PMID- 14973965
TI  - Intravenous immunoglobulin for suspected or subsequently proven infection in
      neonates.
AB  - BACKGROUND: Congenital and nosocomial infections are important causes of neonatal
      morbidity and mortality. Maternal transport of immunoglobulins to the fetus
      mainly occurs after 32 weeks gestation and endogenous synthesis does not begin
      until several months after birth. Administration of intravenous immunoglobulin
      provides IgG that can bind to cell surface receptors, provide opsonic activity,
      activate complement, promote antibody dependent cytotoxicity, and improve
      neutrophilic chemo luminescence. Theoretically infectious morbidity and morbidity
      could be reduced by the administration of intravenous immunoglobulin. OBJECTIVES:
      To assess the effectiveness of intravenous immunoglobulin (IVIG) to reduce
      mortality/morbidity caused by suspected infection in newborn infants. In
      secondary analyses to assess the effectiveness of IVIG to reduce
      mortality/morbidity in those neonates who entered into the studies with suspected
      infection and who later were confirmed as being infected. SEARCH STRATEGY:
      MEDLINE, EMBASE and the Cochrane Library were searched in September 2003. The
      reference lists of identified RCTs, meta-analyses and personal files were
      searched. No language restrictions were applied. Unpublished information was
      requested from and obtained from five researchers (Erdem 1993; Gokalp 1994; Haque
      1988; Mancilla-R 1992; Shenoi 1999). For this update no new trials were
      identified but additional information on one trial (Mancilla-R 1992) was obtained
      in February 2002. SELECTION CRITERIA: The criteria used to select studies for
      inclusion were: 1) DESIGN: RCT (including quasi-randomized trials) 2) Newborn
      infants (< 28 days old)3) INTERVENTION: IVIG for treatment of suspected (and in
      some infants subsequently proved) bacterial/fungal infection compared to placebo
      or no intervention. 4) At least one of the following outcomes was reported:
      mortality during initial hospital stay; length of hospital stay; side effects;
      psychomotor development/growth at follow up. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently abstracted information for the outcomes of interest and
      one researcher (AO) checked for any discrepancies and pooled the results. Typical
      Relative Risk (RR) and Risk Difference (RD) with 95% confidence intervals (CI)
      using the fixed effects model are reported for dichotomous outcomes and weighted
      mean difference (WMD) for continuous data. NNT were to be calculated for outcomes
      that showed a statistically significant reduction in RD. For this update we did
      not calculate the RD and the NNT for the subset of patients, who entered the
      trials with suspected sepsis and who were subsequently proven to have sepsis.
      Such estimates are meaningless as the clinician is unaware at the point of
      starting treatment, whether the infant will have proven sepsis or not. For this
      update we added the I(2) statistic. MAIN RESULTS: Five hundred fifty three
      neonates with suspected infection have been enrolled in RCTs to evaluate the
      effect of IVIG on neonatal outcomes. These studies were undertaken in seven
      countries. Six studies (n = 318) reported on the outcome of mortality for
      randomized patients with clinically suspected infection. The results showed a
      reduction in mortality following IVIG treatment [typical RR 0.63 (95% CI; 0.40,
      1.00), RD -0.09 (95% CI; 0.00, -0.17) of borderline statistical significance.
      Treatment with IVIG (seven trials, n = 262) in cases of subsequently proven
      infection did result in a statistically significant reduction in mortality
      [typical RR 0.55 (95% CI; 0.31, 0.98)In spite of different geographical locations
      of the studies, differences in the mortality in the control groups (range 0% -
      43.8%), the use of different IVIG preparations, and different dosing regimens,
      there was no statistically significant between-study heterogeneity for the
      outcome of mortality in the two analyses. I(2 )= 0%. REVIEWER'S CONCLUSIONS: The
      conclusions did not change in this updated review. There is insufficient evidence
      to support the routine administration of IVIG preparations investigated to date
      to prevent mortality in infants with gated to date to prevent mortality in
      infants with suspected or subsequently proved neonatal infection. Researchers
      should be encouraged to undertake well-designed trials to confirm or refute the
      effectiveness of IVIG to reduce adverse outcomes in neonates with suspected
      infection. Such a trial is currently ongoing in the UK and Australia
      (Brocklehurst 2001). The sample size is 5000 neonates and as of September 2003
      more than 600 patients have been enrolled.

PMID- 14973966
TI  - Breathing exercises for asthma.
AB  - BACKGROUND: There is much anecdotal evidence in Eastern and Western literature
      describing considerable benefits for patients with asthma when treated with
      breathing interventions. The term 'breathing exercise, training and retraining'
      has numerous interpretations depending on the nature of the therapy, therapist
      and cultural background. OBJECTIVES: To assess the evidence for the efficacy of
      breathing retraining in the treatment of patients with asthma. SEARCH STRATEGY:
      Trials were searched for in the Cochrane Airways Group trials register, Cochrane
      Complementary Medicine Field trials register, EMBASE: Physical Medicine &
      Rehabilitation Field, and Databases of the physiotherapy library of current
      research, World Congress of Physical Therapy Proceedings (1995) and AMED (Allied
      & Complementary Medicine Database 1985-2003/4). Hand searching of the Association
      of Chartered Physiotherapists in Respiratory Care Journals was undertaken.
      Chartered physiotherapists in the field of respiratory medicine were contacted
      and appeals made in the 'Physiotherapy' Journal and the Physiotherapy Respiratory
      Care magazine. Searches were undertaken of bibliographies from the included
      studies and other appropriate papers. Authors of included studies were contacted
      for information concerning other relevant trials. SELECTION CRITERIA: Randomised
      or quasi-randomised controlled trials of breathing retraining in patients of all
      ages with a diagnosis of asthma. Breathing retraining should be a major component
      of the treatment intervention. DATA COLLECTION AND ANALYSIS: Two reviewers (EH &
      FR) independently assessed trial quality and extracted data. Authors of included
      trials were contacted for additional data. Where possible adverse effects were
      noted. MAIN RESULTS: Abstracts were identified and 42 full text papers were
      obtained for assessment and possible inclusion. Thirty five studies were
      excluded. A total of five studies were included in the original review. Two
      further studies have been added to this update. Most studies were of small size.
      Two studies demonstrated significant reductions in rescue bronchodilator use and
      three studies showed reductions in acute exacerbations, although these were
      measured in different ways. Two single studies showed significant improvements in
      quality of life measures. Overall, benefits of breathing exercises were found in
      isolated outcome measures in single studies. Five studies compared breathing
      retraining with no active control and two with asthma education control groups.
      REVIEWER'S CONCLUSIONS: Comparisons and conclusions were difficult to evaluate as
      treatment interventions and outcome measurements from the seven trials varied
      considerably. At present therefore no reliable conclusions can be drawn
      concerning the use of breathing exercises for asthma in clinical practice.
      However trends for improvement, notably in quality of life measurements, are
      encouraging and further studies including full descriptions of treatment methods
      and outcome measurements are required.

PMID- 14973967
TI  - Bladder training for urinary incontinence in adults.
AB  - BACKGROUND: Urinary incontinence is a common and distressing problem. Bladder
      training aims to increase the interval between voids and is widely used for the
      treatment of urinary incontinence. OBJECTIVES: To assess the effects of bladder
      training for the treatment of urinary incontinence. SEARCH STRATEGY: We searched
      the Cochrane Incontinence Group trials register (January 2003). The reference
      lists of relevant articles were searched, and trialists contacted for details of
      other trials. Date of the most recent search: January 2003. SELECTION CRITERIA:
      Randomised or quasi-randomised trials of bladder training for the treatment of
      any type of urinary incontinence. DATA COLLECTION AND ANALYSIS: Two reviewers
      assessed trial quality and independently extracted data. Five primary outcomes
      were prespecified: participant's perception of cure of urinary incontinence;
      participant's perception of improvement of urinary incontinence; number of
      incontinent episodes; number of micturitions; and quality of life. Adverse events
      were also noted. Three hypotheses were tested: bladder training is better than no
      bladder training; bladder training is better than other treatments; and combining
      bladder training with another treatment is better than that other treatment
      alone. MAIN RESULTS: We assessed 73 reports of 36 potentially relevant trials; 28
      reports of ten trials were eligible for inclusion with a total of 1366,
      predominantly female, participants. Not all participants' with overactive
      bladder, in five trials had urinary incontinence. Data from five trials with 467
      participants, all female, are therefore included in the review. The quality of
      trials was variable. Few data describing long term follow up are available.Is
      bladder training better than no bladder training? Data were available for 149
      women from two trials comparing bladder training with no bladder training. These
      described only a limited number of prespecified outcomes, which varied across the
      two trials. Point estimates of effect favoured bladder training however
      confidence intervals were wide and no statistically significant differences were
      found for primary outcome variables.Is bladder training better than other
      treatments? Only two trials including 125 women compared bladder training with
      drugs: one with oxybutynin and one with imipramine plus flavoxate. In the former
      trial the only outcomes demonstrating a statistically significant difference were
      participant's perception of cure at six months (RR 1.69; 95% CI 1.21 to 2.34) and
      adverse events (RR 0.03; 95% CI 0.00 to 0.44), both favouring bladder training.
      In the latter trial participant's perception of cure immediately after treatment
      just achieved statistical significance (RR 1.50; 95% CI 1.02 to 2.21) favouring
      bladder training, and this difference was maintained at approximately two months
      post treatment. One comparison of bladder training with pelvic floor muscle
      training plus biofeedback included 132 women: none of the differences in the
      primary outcomes achieved statistical significance.Is combining bladder training
      with another treatment better than that other treatment alone? One trial compared
      pelvic floor muscle training plus biofeedback supplemented with bladder training
      versus pelvic floor muscle training plus biofeedback alone and included 125
      women. Of the primary outcomes both participants' perception of improvement and
      quality of life, both immediately after treatment, achieved statistical
      significance, favouring the bladder training combined with pelvic floor muscle
      training and biofeedback group (perception of improvement: RR 1.18; 95% CI 1.01
      to 1.39; quality of life: MD -47.20; 95% CI -87.03 to -7.37), this was not
      sustained at three months. REVIEWER'S CONCLUSIONS: The limited evidence available
      suggests that bladder training may be helpful for the treatment of urinary
      incontinence, but this conclusion can only be tentative as the trials were of
      variable quality and of small size with wide confidence intervals around the
      point estimates of effect. There was also not enough evidence to determine w
      evidence to determine whether bladder training was useful as a supplement to
      another therapy. Definitive research has yet to be conducted: more research is
      required.

PMID- 14973968
TI  - Cranberries for preventing urinary tract infections.
AB  - BACKGROUND: Cranberries (particularly in the form of cranberry juice) have been
      used widely for several decades for the prevention and treatment of urinary tract
      infections (UTIs). The aim of this review is to assess the effectiveness of
      cranberries in preventing such infections. OBJECTIVES: To assess the
      effectiveness of cranberry juice and other cranberry products in preventing UTIs
      in susceptible populations. SEARCH STRATEGY: Electronic databases and the
      Internet were searched using English and non English language terms; companies
      involved with the promotion and distribution of cranberry preparations were
      contacted; reference lists of review articles and relevant trials were searched.
      Cochrane Central Register of Controlled Trials (CENTRAL - the Cochrane Library,
      issue 1, 2003) was searched in February 2003. SELECTION CRITERIA: All randomised
      or quasi randomised controlled trials of cranberry juice/products for the
      prevention of urinary tract infections in susceptible populations. Trials of men,
      women or children were included. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed and extracted information. Information was collected on
      methods, participants, interventions and outcomes (urinary tract infections
      (symptomatic and asymptomatic), side effects and adherence to therapy). RR were
      calculated where appropriate, otherwise a narrative synthesis was undertaken.
      Quality was assessed using the Cochrane criteria. MAIN RESULTS: Seven trials met
      the inclusion criteria (four cross-over, three parallel group). The effectiveness
      of cranberry juice (or cranberry-lingonberry juice) versus placebo juice or water
      was evaluated in six trials, and the effectiveness of cranberries tablets versus
      placebo was evaluated in two trials (one study evaluated both juice and tablets).
      In two good quality RCTs, cranberry products significantly reduced the incidence
      of UTIs at twelve months (RR 0.61 95% CI:0.40 to 0.91) compared with
      placebo/control in women. One trial gave 7.5 g cranberry concentrate daily (in 50
      ml), the other gave 1:30 concentrate given either in 250 ml juice or in tablet
      form. There was no significant difference in the incidence of UTIs between
      cranberry juice versus cranberry capsules (RR 1.11 95% CI:0.49 to 2.50). Five
      trials were not included in the meta-analyses due to methodological flaws or lack
      of available data. However, only one reported a significant result for the
      outcome of symptomatic UTIs. Side effects were common in all trials, and
      dropouts/withdrawals in several of the trials were high. REVIEWER'S CONCLUSIONS:
      There is some evidence from two good quality RCTs that cranberry juice may
      decrease the number of symptomatic UTIs over a 12 month period in women. If it is
      effective for other groups such as children and elderly men and women is not
      clear. The large number of dropouts/withdrawals from some of the trials indicates
      that cranberry juice may not be acceptable over long periods of time. In addition
      it is not clear what is the optimum dosage or method of administration (e.g.
      juice or tablets). Further properly designed trials with relevant outcomes are
      needed.

PMID- 14973969
TI  - Ketotifen alone or as additional medication for long-term control of asthma and
      wheeze in children.
AB  - BACKGROUND: Ketotifen is an antihistamine which may be used to treat asthma.
      Since administering inhaled therapy to younger children can be difficult, an oral
      agent such as ketotifen offers potential advantages. OBJECTIVES: The objective of
      this review is to determine, whether ketotifen alone or in combination with other
      co-interventions results in better control of asthma in children with asthma
      and/or wheezing and examine its safety profile. SEARCH STRATEGY: We searched the
      Cochrane Airways Group register of trials (based on MEDLINE, EMBASE, CINAHL and
      handsearched respiratory journals) and reference lists of articles. The latest
      search was carried out in October 2002. SELECTION CRITERIA: Clinical studies had
      to be randomised-controlled and double-blinded, comparing oral ketotifen with
      placebo in children with asthma and/or wheeze for at least eight weeks at a dose
      not less than one mg daily. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently performed selection of trials, quality assessment and data
      extraction; a third reviewer was included in the consensus process if necessary.
      MAIN RESULTS: A total of 26 relevant studies involving 1826 participants were
      included in this review. Children's age ranged from 4 months to 18 years and
      ketotifen was given between 10 and 32 weeks. The proportion of children able to
      reduce or stop their bronchodilator use within 12 to 16 weeks of treatment was
      significantly higher in the ketotifen group (relative risk 2.39, 95% CI 1.64 to
      3.48) based on four trials; this result was statistically significant in a
      subgroup of two trials with well described and adequate method of blinding.
      Statistically significant beneficial effects of ketotifen were also observed in
      the following secondary outcomes: efficacy evaluated by physician (10 trials) and
      parents/patients (7 trials), asthma symptom score (4 trials), asthma
      exacerbations (2 trials), and reduction in use of oral steroids (4 trials).
      However, sub-group analyses of trials with well described and adequate method of
      blinding was only significant for the outcome asthma symptom score and non
      significant for the remaining secondary outcomes. Reported side effects were more
      frequent in the ketotifen group (sedation: 21%, weight gain: 27%) than in the
      placebo group (sedation: 12%, weight gain: 17%). REVIEWER'S CONCLUSIONS: Evidence
      from randomised controlled trials indicates that ketotifen alone or in
      combination with other co-interventions improves control of asthma and wheezing
      in children with mild and moderate asthma. However due to the high proportion of
      children with atopy in some trials the results cannot necessarily be generalised
      to all asthmatic children. The benefit is obtained at the cost of minor side
      effects, namely sedation and weight gain. The validity of this conclusion is
      limited by the low reported, methodological quality of included trials.

PMID- 14973970
TI  - Pneumococcal vaccines for preventing otitis media.
AB  - BACKGROUND: Acute otitis media (AOM) is one of the most common diseases in early
      infancy and childhood. Long term effects of recurrent episodes of otitis media,
      rapid emergence of drug resistant bacteria associated with AOM worldwide and huge
      estimated direct and indirect annual costs associated with otitis media have
      emphasized the need for an effective vaccination program to prevent episodes of
      AOM. OBJECTIVES: The object of this review was to assess the effect of
      pneumococcal vaccination in preventing AOM in children up to 12 years of age.
      SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (issue 2, 2003) which contains the Cochrane Acute Respiratory Infection
      Group's specialised register (30th June 2003), MEDLINE (January 1966 to June
      2003), EMBASE (January 1990 to June 2003) and reference lists of all studies and
      review articles retrieved. We also contacted two vaccine manufacturers and first
      or corresponding authors of some of the included studies. SELECTION CRITERIA:
      Randomised controlled clinical trials of pneumococcal vaccination with prevention
      of AOM as outcome in children aged 12 years or younger and a follow-up of at
      least six months after vaccination. DATA COLLECTION AND ANALYSIS: Five reviewers
      independently assessed trial quality and two reviewers extracted data. Two study
      authors were contacted. MAIN RESULTS: Eight trials on 8-to 14-valent pneumococcal
      polysaccharide vaccine (PPV) and four trials on 7-to 9-valent pneumococcal
      conjugate vaccine (PCV) were included. The highest efficacy of PPV was found in
      children aged 24 months and older: the rate ratio was 0.779 [95% CI: 0.625
      0.970]. PPV has little effect on the prevention of AOM in children without
      documented prior episodes of AOM and only a moderate effect in the group of
      children with documented AOM episodes prior to vaccination. Pooled results of the
      four PCV trials in infants vaccinated as early as two months of age and toddlers
      attending daycare and toddlers with recurrent AOM showed only a small effect on
      prevention of AOM (rate ratio 0.921; 95% CI: 0.894-0.950). REVIEWER'S
      CONCLUSIONS: Based on the currently available results of the effectiveness of
      pneumococcal vaccination for the prevention of AOM, a large scale use of
      pneumococcal polysaccharide and conjugate vaccination for this specific
      indication is not yet recommended. So far, pneumococcal conjugate vaccinations
      are not indicated in the management of recurrent AOM in toddlers and older
      children. The results of currently ongoing trials of 9- and 11-valent conjugate
      vaccines should provide more information as to whether pneumococcal vaccines are
      more effective in specific high-risk populations like infants and older children
      with recurrent AOM or immunodeficiency.

PMID- 14973971
TI  - Beta2-agonists for acute bronchitis.
AB  - BACKGROUND: The optimal treatment for acute bronchitis is not clear. Because many
      patients with acute bronchitis have airflow limitation as well as cough, beta2
      agonists may be useful. OBJECTIVES: To determine whether beta2-agonists improve
      the symptoms of acute bronchitis in patients who do not have underlying pulmonary
      disease. SEARCH STRATEGY: The Cochrane Library (through August 2000), MEDLINE
      (1966 to 2000), EMBASE (1974 to 2000), and Conference Proceedings using
      "bronchodilator (exp)", "adrenergic beta-agonist (exp)", or "sympathomimetics
      (exp)" and "bronchitis" or "cough"; Science Citation Index for referenced
      publications; and letters to manufacturers of beta2-agonists. An updated search
      of the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 3, 2003);
      MEDLINE (January 2000 to July 2003); EMBASE (January 2000 to July 2003) was run
      in July 2003. SELECTION CRITERIA: Trials in which patients (adults or children
      over two years of age) without known pulmonary disease who were diagnosed with
      acute bronchitis or acute cough without other cause were randomized to beta2
      agonist versus placebo, no treatment, or alternative treatment. DATA COLLECTION
      AND ANALYSIS: Three reviewers independently first selected outcomes and evaluated
      trial quality while blinded to study results, and then extracted data. Trials in
      children and in adults were analyzed separately. MAIN RESULTS: Two trials in
      children (n = 109) with acute cough and no evidence of airway obstruction did not
      find any benefits from beta2-agonists. Combined data did not show a significant
      difference in daily cough scores between patients given oral beta2-agonists and
      those in the control groups. Five trials in adults (n = 418) with acute cough or
      acute bronchitis had mixed results, but overall summary statistics did not reveal
      any significant benefits from oral (three trials) nor inhaled (two trials) beta2
      agonists. There were no significant differences in daily cough scores nor in the
      number of patients still coughing after seven days (control rate 73%; RR = 0.77,
      95% CI 0.54-1.09). Subgroups of patients with evidence of airflow limitation had
      lower symptom scores if given beta2-agonists in one trial; and the trials that
      did note quicker resolution of cough in patients given beta2-agonists were those
      that had a higher proportion of patients with wheezing at baseline. Patients
      given beta2-agonists were more likely to report tremor, shakiness, or nervousness
      than patients in the control groups (for trials in children control rate 0%; RR
      6.76, 95% CI 0.86 to 53.12, NNH 9, 95% CI 5 to 100; for trials in adults, control
      rate 11%; RR 7.94, 95% CI 1.17 to 53.94, NNH 2.3, 95% CI 2 to 3). REVIEWER'S
      CONCLUSIONS: There is no evidence to support using beta2-agonists in children
      with acute cough who do not have evidence of airflow obstruction. There is also
      little evidence that the routine use of beta2-agonists for adults with acute
      cough is helpful. These agents may reduce symptoms, including cough, in patients
      with evidence of airflow obstruction; but this potential benefit is not well
      supported by the available data and must be weighed against the adverse effects
      associated with beta2-agonists.

PMID- 14973972
TI  - Oral immunoglobulin for preventing necrotizing enterocolitis in preterm and low
      birth-weight neonates.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is the most common emergency of the
      gastrointestinal tract occurring in the neonatal period. There have been
      published reports which suggest that oral immunoglobulins IgA and IgG produce an
      immunoprotective effect in the gastrointestinal mucosa. This systematic review
      was undertaken to clarify the issue. OBJECTIVES: To assess whether oral
      immunoglobulin administered to preterm and low birth-weight neonates reduces the
      incidence of necrotizing enterocolitis without adverse effects. SEARCH STRATEGY:
      The databases MEDLINE, CINAHL, EMBASE (1966 to October 26, 2003) and the Cochrane
      Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3,
      2003) were searched. Proceedings of the Perinatal Society of Australia and New
      Zealand were hand searched. The computer neonatal discussion site 'Nicu Net' was
      also used. Additionally, all references in the identified trials were checked and
      authors were contacted to request any additional published or unpublished data.
      No new trials were identified. SELECTION CRITERIA: All randomised or quasi
      randomised controlled trials where oral immunoglobulins were used as prophylaxis
      against necrotizing enterocolitis in preterm (<37 weeks gestation) and/or low
      birth-weight (<2500 gms) neonates. DATA COLLECTION AND ANALYSIS: The procedures
      of the Cochrane Neonatal Review Group (CNRG) were used. The two reviewers
      independently assessed the trials for their methodological quality and subsequent
      inclusion in the review. Relative risk (RR), risk difference (RD), and number
      needed to treat (NNT) were used in the analysis. MAIN RESULTS: Five studies on
      oral immunoglobulin for the prevention of necrotizing enterocolitis were
      identified of which three met the inclusion criteria. In this review of the three
      eligible trials (including a total of 2095 neonates) the oral administration of
      IgG or an IgG/IgA combination did not result in a significant reduction in the
      incidence of definite NEC [RR 0.84 (95% CI 0.57, 1.25), RD -0.01 (95% CI -0.03,
      0.01)], suspected NEC [RR 0.84 (95% CI 0.49, 1.46), RD -0.01 (95% CI -0.02,
      0.01)], need for surgery [RR 0.21 (95% CI 0.02, 1.75), RD -0.03 (95% CI -0.06,
      0.00)] or death from NEC [RR 1.10 (95% CI 0.47, 2.59), RD 0.00 (95% CI -0.01,
      0.01)]. REVIEWER'S CONCLUSIONS: Based on the available trials, the evidence does
      not support the administration of oral immunoglobulin for the prevention of NEC.
      There are no randomised controlled trials of oral IgA alone for the prevention of
      NEC.

PMID- 14973973
TI  - Nutritional supplementation for hip fracture aftercare in the elderly.
AB  - BACKGROUND: Fractures of the hip are an important cause of later ill health and
      mortality in elderly people. People with hip fractures are often malnourished at
      the time of fracture, and have poor food intake in hospital. OBJECTIVES: This
      review assesses the effects of nutritional interventions in elderly people
      recovering from hip fracture. SEARCH STRATEGY: We searched the Cochrane
      Musculoskeletal Injuries Group specialised register, the Cochrane Central
      Register of Controlled Trials (The Cochrane Library issue 2, 2003), MEDLINE (1966
      to July 2003), Nutrition Abstracts and Reviews (1984 to March 2003), EMBASE (1980
      to week 29 2003), BIOSIS (1985 to July 2003), CINAHL (1982 to July 2003),
      HEALTHSTAR (1975 to March 2002), the National Research Register and reference
      lists. We contacted investigators, and handsearched the American Journal of
      Clinical Nutrition, Proceedings of the Nutrition Society, Clinical Nutrition and
      the Journal of Parenteral and Enteral Nutrition. SELECTION CRITERIA: Randomised
      and quasi-randomised trials of nutritional interventions of mainly older patients
      (aged over 65 years) with hip fracture. DATA COLLECTION AND ANALYSIS: Trial
      allocation to included, excluded and awaiting assessment categories, was by
      consensus. Both reviewers independently extracted data and assessed trial
      quality. Additional information was sought from all trialists. Pooling of data
      for primary outcomes and select exploratory analyses were undertaken. MAIN
      RESULTS: Seventeen randomised trials involving 1266 participants were included.
      Overall the quality of trials was poor; specifically in terms of allocation
      concealment, assessor blinding and intention to treat analysis. This, and the
      limited availability of outcome data, mean that the following results must be
      interpreted with caution. Oral multinutrient feeds (providing non-protein energy,
      protein, some vitamins and minerals), evaluated by seven trials, may reduce
      unfavourable outcome (death or complications) (14/66 versus 26/73; relative risk
      0.52, 95% confidence interval 0.32 to 0.84), but did not demonstrate an effect on
      mortality (12/91 versus 14/97; relative risk 0.85, 95% confidence interval 0.42
      to 1.70). Four trials, examining nasogastric multinutrient feeding, showed no
      evidence for an effect on mortality (relative risk 0.99, 95% confidence interval
      0.50 to 1.97), but the studies were heterogeneous regarding case-mix.
      Insufficient information was provided to evaluate unfavourable outcome. The
      effect of protein in an oral feed, tested in three trials, showed no evidence for
      an effect on mortality (relative risk 1.38, 95% confidence interval 0.82 to
      2.34). It may have reduced the number of long term complications and days spent
      in rehabilitation wards. Two trials, testing intravenous thiamin (vitamin B1) and
      other water soluble vitamins, or 1-alpha-hydroxycholecalciferol (an active form
      of vitamin D) respectively, produced no evidence of benefit for either vitamin
      supplement. REVIEWER'S CONCLUSIONS: The strongest evidence for the effectiveness
      of nutritional supplementation exists for oral protein and energy feeds, but the
      evidence is still very weak. Future trials are required which overcome the
      defects of the reviewed studies, particularly inadequate size, methodology and
      outcome assessment.

PMID- 14973975
TI  - Glucocorticoids for croup.
AB  - BACKGROUND: Since the initial version of this systematic review in 1997, a number
      of randomised trials examining the benefit of glucocorticoids have been
      published, reflecting a continued interest in the use of glucocorticoids to treat
      patients with croup. The objective of this review was to provide evidence to
      guide clinicians in their treatment of patients with croup by determining the
      effectiveness of glucocorticoids and to identify areas of uncertainty for future
      research. OBJECTIVES: To determine the effect of glucocorticoids for children
      with croup. SEARCH STRATEGY: We searched The Cochrane Central Register of
      Controlled Trials (CENTRAL) (issue 1, 2003), MEDLINE (January 1966 to April 2003)
      and Excerpta Medica/EMBASE (January 1974 to August 2003). We also contacted
      authors of identified croup trials published in the last ten years to inquire
      about additional published or unpublished trials. SELECTION CRITERIA: Randomised
      controlled trials that examine children with croup and objectively measure the
      effectiveness of glucocorticoid treatment. DATA COLLECTION AND ANALYSIS: Based on
      review of the title and abstract (when available), two researchers identified
      studies for potential relevance. The complete text was retrieved and using a
      priori inclusion criteria, the studies were independently reviewed for relevance
      by two reviewers. Two observers independently assessed quality. Differences with
      respect to inclusion status and quality assessment were resolved by consensus.
      Data were extracted using a structured form by one reviewer and checked for
      accuracy by a second reviewer. Standard statistical analyses were performed. MAIN
      RESULTS: Thirty-one studies were deemed relevant for inclusion (N = 3736).
      Glucocorticoid treatment was associated with an improvement in the Westley score
      at six hours with a weighted mean difference of -1.2 (95% confidence interval 
      1.6 to -0.8) and at 12 hours -1.9 (-2.4 to -1.3); at 24 hours this improvement
      was no longer significant (-1.3, -2.7 to 0.2). Fewer return visits and/or
      (re)admissions occurred in patients treated with glucocorticoids (relative risk
      0.50; 0.36 to 0.70). Length of time spent in accident and emergency or hospital
      (weighted mean difference 12 hours, five to 19 hours) was significantly decreased
      for patients treated with glucocorticoids. Use of epinephrine decreased for
      children treated with a glucocorticoid (risk difference 10%; 1 to 20). No other
      decreases in additional treatments were found in the primary analysis.
      Publication bias does not impact results importantly. No between-trial
      significant differences were found between populations with mild and moderate
      croup. Oral dexamethasone may be superior to intramuscular dexamethasone.
      REVIEWER'S CONCLUSIONS: Dexamethasone and budesonide are effective in relieving
      the symptoms of croup as early as six hours after treatment. Fewer return visits
      and/or (re)admissions are required and the length of time spent in hospital is
      decreased in inpatients. Dexamethasone is also effective in mild croup
      populations. Research is required to examine the most beneficial method for
      disseminating croup practice guidelines and to increase the uptake of evidence to
      improve outcomes.

PMID- 14973974
TI  - Desmopressin for minimising perioperative allogeneic blood transfusion.
AB  - BACKGROUND: Public concerns regarding the safety of transfused blood have
      prompted re-consideration of the use of allogeneic (from an unrelated donor) red
      blood cell (RBC) transfusion, and of a range of techniques designed to minimise
      transfusion requirements. OBJECTIVES: To examine the evidence for the efficacy of
      desmopressin acetate (1-deamino-8-D-arginine-vasopressin; DDAVP), in reducing
      perioperative blood loss and the need for red cell transfusion in patients who do
      not have congenital bleeding disorders. SEARCH STRATEGY: Articles were identified
      by: computer searches of MEDLINE, EMBASE, Current Contents (to May 2003), and the
      Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue
      1, 2003). References in the identified trials and review articles were searched
      and authors contacted to identify additional studies. SELECTION CRITERIA:
      Controlled parallel group trials in which adult patients, scheduled for non
      urgent surgery, were randomised to DDAVP, or to a control group, who did not
      receive the intervention. DATA COLLECTION AND ANALYSIS: Trial quality was
      assessed using criteria proposed by Schulz et al. (Schulz 1995) and Jadad et al.
      (Jadad 1996). Main outcomes measured were: the number of patients exposed to
      allogeneic red cell transfusion, and the amount of blood transfused. Other
      outcomes measured were: re-operation for bleeding, blood loss, post-operative
      complications (thrombosis, infection, non-fatal myocardial infarction),
      mortality, and length of hospital stay (LOS). MAIN RESULTS: Eighteen trials of
      DDAVP (n=1295) reported data on the number of patients transfused with allogeneic
      RBC transfusion. In subjects treated with DDAVP, the pooled relative risk of
      exposure to perioperative allogeneic RBC transfusion was 0.95 (95%CI = 0.86 to
      1.06). The use of DDAVP did not significantly reduce blood loss; weighted mean
      difference (WMD) = -114.3ml: 95% confidence interval (95%CI) = -258.8 to 30.2ml
      per patient) or the volume of RBC transfused (WMD = -0.35 units: 95%CI = -0.70 to
      0.01 units). In DDAVP-treated patients the relative risk of requiring re
      operation due to bleeding was 0.69 (95%CI = 0.26 to 1.83). There was no
      statistically significant effect overall for mortality and non-fatal myocardial
      infarction in DDAVP-treated patients compared with control (RR = 1.72: 95%CI =
      0.68 to 4.33) and (RR = 1.38: 95%CI = 0.77 to 2.50) respectively. REVIEWER'S
      CONCLUSIONS: There is no convincing evidence that desmopressin minimises
      perioperative allogeneic RBC transfusion in patients who do not have congenital
      bleeding disorders. These data suggest that there is no benefit from using DDAVP
      as a means of minimising perioperative allogeneic RBC transfusion.

PMID- 14973976
TI  - Homoeopathic Oscillococcinum for preventing and treating influenza and influenza
      like syndromes.
AB  - BACKGROUND: Influenza is a highly infectious viral disease that is particularly
      common in the winter months. Oscillococcinum is a patented, commercially
      available homoeopathic medicine. The rationale for its use in influenza comes
      from the homoeopathic principle of 'let like be cured by like'. The medicine is
      manufactured from wild duck heart and liver, which are said to be reservoirs for
      influenza viruses. OBJECTIVES: To determine whether homoeopathic Oscillococcinum
      or similar medicines are more effective than placebo in the prevention and
      treatment of influenza and influenza-like syndromes. SEARCH STRATEGY: The
      Cochrane Central Register of Controlled Trials (CENTRAL) issue 2, 2003; MEDLINE
      (January 1966 to June 2003) and EMBASE (1980 to June 2003) were searched, using
      the term "homeopathy" with "influenza", "respiratory tract", "infection",
      "cough", "virus" and "fever". The manufacturers of Oscillococcinum were contacted
      for information. SELECTION CRITERIA: Placebo-controlled trials of Oscillococcinum
      or homeopathically-prepared influenza virus, influenza vaccine or avian liver in
      the prevention and treatment of influenza and influenza-like syndromes. DATA
      COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed methodological
      quality independently. MAIN RESULTS: Seven studies were included in the review,
      three prevention trials (n = 2265) and four treatment trials (n = 1194). Only for
      two studies was there sufficient information to complete data extraction fully.
      There was no evidence that homoeopathic treatment can prevent influenza-like
      syndrome (relative risk 0.64, 95% confidence interval 0.28 to 1.43).
      Oscillococcinum treatment reduced length of influenza illness by 0.28 days (95%
      confidence interval 0.50 to 0.06). Oscillococcinum also increased the chance of a
      patient considering treatment effective (relative risk 1.08; 95% CI 1.17, 1).
      REVIEWER'S CONCLUSIONS: Though promising, the data are not strong enough to make
      a general recommendation to use Oscillococcinum for first-line treatment of
      influenza and influenza-like syndrome. Further research is warranted but required
      sample sizes are large. Current evidence does not support a preventative effect
      of Oscillococcinum-like homeopathic medicines in influenza and influenza-like
      syndromes.

PMID- 14973977
TI  - Interventions for treating oral candidiasis for patients with cancer receiving
      treatment.
AB  - BACKGROUND: Treatment of cancer is increasingly effective but is associated with
      short and long-term side effects. Oral side effects, including oral candidiasis,
      remain a major source of illness despite the use of a variety of agents to treat
      them. OBJECTIVES: To assess the effectiveness of interventions for the treatment
      of oral candidiasis for patients with cancer receiving chemotherapy and or
      radiotherapy. SEARCH STRATEGY: Computerised searches of Cochrane Oral Health
      Group's Trials Register, CENTRAL, MEDLINE and EMBASE were undertaken. Reference
      lists from relevant articles were searched and the authors of eligible trials
      were contacted to identify trials and obtain additional information.Date of the
      most recent searches: August 2003: (CENTRAL) (The Cochrane Library Issue 3,
      2003). SELECTION CRITERIA: All randomised controlled trials comparing agents
      prescribed to treat oral candidiasis in people receiving chemotherapy or
      radiotherapy for cancer. The outcomes were eradication of oral candidiasis,
      dysphagia, systemic infection, amount of analgesia, length of hospitalisation,
      cost and patient quality of life. DATA COLLECTION AND ANALYSIS: Data were
      independently extracted, in duplicate, by two reviewers. Authors were contacted
      for details of randomisation and withdrawals and a quality assessment was carried
      out. The Cochrane Oral Health Group statistical guidelines were followed and
      relative risk values calculated using random effects models where significant
      heterogeneity was detected (P < 0.1). MAIN RESULTS: Eight trials involving 418
      patients, satisfied the inclusion criteria and are included in this review. Only
      two agents, each in single trials, were found to be effective for eradicating
      oral candidiasis. A drug absorbed from the gastrointestinal tract, ketoconazole,
      was more beneficial than placebo in eradicating oral candidiasis (relative risk
      (RR) = 0.35, 95% confidence interval (CI) 0.20 to 0.61) and clotrimazole, at a
      higher dose of 50 mg was more effective than a lower 10 mg dose in eradicating
      oral candidiasis, when assessed mycologically (RR = 0.47, 95% CI 0.25 to 0.89).
      Another trial demonstrated no statistically significant difference between a 10
      mg dose of the partially absorbed drug, clotrimazole, and placebo. No differences
      were found when comparing different absorbed drugs; and comparing absorbed drugs
      with drugs which are not absorbed. REVIEWER'S CONCLUSIONS: There is weak and
      unreliable evidence that the absorbed drug, ketoconazole, may eradicate oral
      candidiasis and that a higher dose of the partially absorbed drug, clotrimazole,
      may give greater benefit than a lower 10 mg dose, however, researchers may wish
      to prevent rather than treat oral candidiasis. Further well designed, placebo
      controlled trials assessing the effectiveness of old and new interventions for
      treating oral candidiasis are needed.

PMID- 14973978
TI  - Laser prostatectomy for benign prostatic obstruction.
AB  - BACKGROUND: Symptomatic benign prostatic obstruction is a common problem for
      older men. The gold standard treatment, transurethral resection of the prostate
      (TURP), significantly improves urinary symptoms and urinary flow. However, TURP
      has up to a 20% morbidity. Currently, there are a number of minimally invasive
      procedures that may be safe, effective alternatives to TURP. One promising
      surgical technique is laser prostatectomy. OBJECTIVES: To assess the therapeutic
      efficacy and safety of laser prostatectomy techniques for treating men with
      symptomatic benign prostatic obstruction. SEARCH STRATEGY: Randomized controlled
      trials were identified from the Cochrane Collaboration Library, MEDLINE, EMBASE,
      bibliographies of retrieved articles and reviews, and contacting expert relevant
      trialists and laser manufacturers. SELECTION CRITERIA: All randomized controlled
      trials evaluating laser prostatectomy treatment for men with symptomatic BPH.
      Trials were eligible if they (1) were randomized comparisons of a laser technique
      with TURP, (2) included at least 10 men with BPO in each treatment arm, (3)
      provided at least 6-months follow-up, and (4) included clinical outcomes such as
      urologic symptom scales or urodynamic measurements. DATA COLLECTION AND ANALYSIS:
      Data extraction and assessment of methodologic quality was performed
      independently by two reviewers. Information on study design, subject and
      treatment characteristics, adverse events, urinary symptoms, and urinary flow
      were extracted using a standard form. MAIN RESULTS: 20 studies involving 1898
      subjects were evaluated, including studies 4 with multiple comparisons. We found
      8 comparisons of TURP with contact lasers, 8 with non-contact lasers, 4 with
      hybrid techniques, and one with interstitial laser coagulation (ILC). Two studies
      compared transurethral electrovaporization (TUVP) with contact lasers, one study
      compared interstitial laser coagulation with transurethral microwave
      thermotherapy (TUMT), and one study compared holmium contact lasers (HoLRP) with
      open prostatectomy. Among the studies comparing laser prostatectomy with TURP,
      follow-up duration ranged from 6 to 36 months. Mean age (67.2 yrs), mean baseline
      symptom score (20.2), and mean baseline peak urinary flow (9.2 ml/s) did not
      differ by treatment group. The pooled percentage improvements for mean urinary
      symptoms ranged from 59% to 68% with lasers and 63% to 77% with TURP. The
      improvements for mean peak urinary flow ranged from 56% to 119% with lasers and
      96% to 127% with TURP. Overall, laser subjects were less likely to receive
      transfusions or develop strictures and their hospitalizations were shorter. Non
      contact laser subjects were more likely to have dysuria, urinary tract infection,
      and retention. Re-operation occurred more often following laser procedures.
      REVIEWER'S CONCLUSIONS: Laser techniques are a useful alternative to TURP for
      treating BPO. Small sample sizes and differences in study design limit any
      definitive conclusions regarding the preferred type of laser technique. Data were
      insufficient to compare laser techniques with other minimally invasive
      procedures.

PMID- 14973979
TI  - Screening for lung cancer.
AB  - BACKGROUND: While population based screening for lung cancer has not been adopted
      by most countries, it is not clear whether sputum examinations, chest radiography
      or newer methods such as computed tomography are effective in reducing mortality
      from lung cancer. OBJECTIVES: To determine whether screening for lung cancer
      using regular sputum examinations or chest radiography or CT chest reduces lung
      cancer mortality. SEARCH STRATEGY: Electronic databases (the Cochrane Central
      Register of Controlled Trials, MEDLINE, PREMEDLINE and EMBASE; 1966 to July 2000)
      ), bibliographies, hand searching of a journal and discussion with experts were
      used to identify published and unpublished trials. SELECTION CRITERIA: Controlled
      trials of screening for lung cancer using sputum examinations, chest radiography
      or CT chest. DATA COLLECTION AND ANALYSIS: Intention to screen analysis was
      performed. Where there was significant statistical heterogeneity relative risks
      were reported using the random effects model, but for other outcomes the fixed
      effect model was used. MAIN RESULTS: Seven trials were included (6 randomised
      controlled studies and 1 non-randomised controlled trial) with a total of 245,610
      subjects. There were no studies with an unscreened control group. Frequent
      screening with chest x-rays was associated with an 11% relative increase in
      mortality from lung cancer compared with less frequent screening (RR 1.11, CI:
      1.00-1.23). A non statistically significant trend was observed to reduced
      mortality from lung cancer when screening with chest x-ray and sputum cytology
      was compared with chest x-ray alone (RR 0.88, CI:0.74-1.03). Several of the
      included studies had potential methodological weaknesses. There were no
      controlled studies of spiral CT. REVIEWER'S CONCLUSIONS: The current evidence
      does not support screening for lung cancer with chest radiography or sputum
      cytology. Frequent chest x-ray screening might be harmful. Further,
      methodologically rigorous trials are required.

PMID- 14973980
TI  - Position for women during second stage of labour.
AB  - BACKGROUND: For centuries, there has been controversy around whether being
      upright (sitting, birthing stools, chairs, squatting) or lying down have
      advantages for women delivering their babies. OBJECTIVES: To assess the benefits
      and risks of the use of different positions during the second stage of labour
      (i.e. from full dilatation of the cervix). SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group trials register (16 April 2003).
      SELECTION CRITERIA: Trials that used randomised or quasi-randomised allocation
      and appropriate follow up and compared various positions assumed by pregnant
      women during the second stage of labour. DATA COLLECTION AND ANALYSIS: We
      independently assessed the trials for inclusion and extracted the data. MAIN
      RESULTS: Results should be interpreted with caution as the methodological quality
      of the 19 included trials (5764 participants) was variable. Use of any upright or
      lateral position, compared with supine or lithotomy positions, was associated
      with: reduced duration of second stage of labour (10 trials: mean 4.29 minutes,
      95% confidence interval (CI) 2.95 to 5.64 minutes) - this was largely due to a
      considerable reduction in women allocated to the use of the birth cushion; a
      small reduction in assisted deliveries (18 trials: relative risk (RR) 0.84, 95%
      CI 0.73 to 0.98); a reduction in episiotomies (12 trials: RR 0.84, 95% CI 0.79 to
      0.91); an increase in second degree perineal tears (11 trials: RR 1.23, 95% CI
      1.09 to 1.39); increased estimated blood loss greater than 500 ml (11 trials: RR
      1.68, 95% CI 1.32 to 2.15); reduced reporting of severe pain during second stage
      of labour (1 trial: RR 0.73, 95% CI 0.60 to 0.90); fewer abnormal fetal heart
      rate patterns (1 trial: RR 0.31, 95% CI 0.08 to 0.98). REVIEWER'S CONCLUSIONS:
      The tentative findings of this review suggest several possible benefits for
      upright posture, with the possibility of increased risk of blood loss greater
      than 500 ml. Women should be encouraged to give birth in the position they find
      most comfortable. Until such time as the benefits and risks of various delivery
      positions are estimated with greater certainty, when methodologically stringent
      trials' data are available, women should be allowed to make informed choices
      about the birth positions in which they might wish to assume for delivery of
      their babies.

PMID- 14973981
TI  - Parent-training programmes for improving maternal psychosocial health.
AB  - BACKGROUND: Mental health problems are common and there is evidence to suggest
      that the origins of such problems lie in infancy and childhood. In particular,
      there is evidence from a range of studies to suggest that maternal psychosocial
      health can have a significant effect on the mother-infant relationship, and that
      this in turn can have consequences for both the short and long-term psychological
      health of the child. The use of parenting programmes is increasing in the UK and
      elsewhere and evidence of their effectiveness in improving outcomes for children
      has been provided. Evidence is now required of their effectiveness in improving
      outcomes for mothers. OBJECTIVES: The objective of this review is to address
      whether group-based parenting programmes are effective in improving maternal
      psychosocial health including anxiety, depression, and self-esteem. SEARCH
      STRATEGY: A range of biomedical, social science, educational and general
      reference electronic databases were searched including MEDLINE, EMBASE CINAHL,
      PsychLIT, ERIC, ASSIA, Sociofile and the Social Science Citation Index. Other
      sources of information included the Cochrane Library (SPECTR, CENTRAL), and the
      National Research Register (NRR). SELECTION CRITERIA: Only randomised controlled
      trials were included in which participants had been randomly allocated to an
      experimental and a control group, the latter being a waiting-list, no-treatment
      or a placebo control group. Studies had to include at least one group-based
      parenting programme, and one standardised instrument measuring maternal
      psychosocial health. DATA COLLECTION AND ANALYSIS: A systematic critical
      appraisal of all included studies was undertaken using a modified version of the
      Journal of the American Medical Association (JAMA) published criteria. The
      treatment effect for each outcome in each study was standardised by dividing the
      mean difference in post-intervention scores for the intervention and treatment
      group, by the pooled standard deviation, to produce an effect size. Where
      appropriate the results were then combined in a meta-analysis using a fixed
      effect model, and 95% confidence intervals were used to assess the significance
      of the findings. MAIN RESULTS: A total of 23 studies were included in the
      original review which was increased to 26 at the first udate (2003). Of these 20
      provided sufficient data to calculate effect sizes. The 20 studies provided a
      total of 64 assessments of outcome on a range of aspects of psychosocial
      functioning including depression, anxiety, stress, self-esteem, social
      competence, social support, guilt, mood, automatic thoughts, dyadic adjustment,
      psychiatric morbidity, irrationality, anger and aggression, mood, attitude,
      personality, and beliefs. Data sufficient to combine in a meta-analysis existed
      for only five outcomes (depression; anxiety/stress; self-esteem; social support;
      and relationship with spouse/marital adjustment). The results of the meta
      analyses show statistically significant results favouring the intervention group
      for depression; anxiety/stress; self-esteem; and relationship with spouse/marital
      adjustment. The meta-analysis of the social support data showed no evidence of
      effectiveness. Of the remaining data that it was not possible to combine in a
      meta-analysis, approximately 22% of the outcomes measured, showed significant
      differences between the intervention group and the control group. A further 40%
      showed non-significant differences favouring the intervention group.
      Approximately one-third of outcomes showed no evidence of effectiveness.A meta
      analysis of the follow-up data on three outcomes was also conducted - depression,
      self-esteem and relationship with spouse/marital adjustment. The results show
      that there was a continued improvement in self-esteem, depression, and marital
      adjustment at follow-up, although the latter two findings were not statistically
      significant. This review has been updated (2003) with the addition of 3 new
      included studies. A number of additional excluded studies have also been added.
      There is one additional study awaiting 03) with the addition of 3 new included
      studies. A number of additional excluded studies have also been added. There is
      one additional study awaiting assessment and 2 ongoing studies listed for
      inclusion at a future update of this review. The size of effect for the main
      outcomes has not been substantially altered by this update. Additional
      sensitivity analyses to assess the impact of quasi randomised studies on the
      result have also been added. Where the quasi randomised studies are excluded from
      the analysis, the result was found to be slightly more conservative. REVIEWER'S
      CONCLUSIONS: It is suggested that parenting programmes can make a significant
      contribution to the short-term psychosocial health of mothers. However, there is
      currently a paucity of evidence concerning whether these results are maintained
      over time, and the limited follow-up data which are available show equivocal
      results. This points to the need for further evidence concerning the long-term
      effectiveness of parenting programmes on maternal mental health. Whilst the
      results of this review are positive overall, some studies showed no effect.
      Further research is needed to assess which factors contribute to successful
      outcomes in these programmes with particular attention being paid to the quality
      of delivery.These results suggest that parenting programmes have a potential role
      to play in the promotion of mental health.

PMID- 14973982
TI  - Intravenous immunoglobulin for Guillain-Barre syndrome.
AB  - BACKGROUND: Guillain-Barre syndrome is an acute, paralysing, inflammatory
      peripheral nerve disease. Intravenous immunoglobulin purified from donated blood
      is beneficial in other autoimmune diseases. OBJECTIVES: We aimed to determine the
      efficacy of intravenous immunoglobulin for treating Guillain-Barre syndrome.
      SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group register
      (search updated 11 February 2003), MEDLINE and EMBASE (from January 2000 to
      February 2003) using Guillain-Barre syndrome and acute polyradiculoneuritis as
      the search terms. We also searched bibliographies of trials and made contact with
      their authors and other experts. SELECTION CRITERIA: We included all randomised
      and quasi-randomised trials. DATA COLLECTION AND ANALYSIS: Two reviewers examined
      the titles and abstracts of all the papers retrieved by the search, extracted the
      data and assessed the quality of the trials independently. MAIN RESULTS: Two
      trials comparing intravenous immunoglobulin with supportive treatment were
      inadequate to establish its value. Another Cochrane systematic review has shown
      that plasma exchange hastens recovery. We found six randomised trials that
      compared intravenous immunoglobulin with plasma exchange. In a meta-analysis of
      five trials involving 536, mostly adult, participants who were unable to walk
      unaided and had been ill for less than two weeks. The primary outcome measure in
      this review was the change in a seven grade disability scale four weeks after
      randomisation. The weighted mean difference of this measure was not statistically
      significant, being only 0.04 (95% CI -0.26 to 0.19) of a disability grade more
      improvement in the intravenous immunoglobulin group than the plasma exchange
      group. There were also no statistically significant differences in time to walk
      unaided, mortality, and proportion of participants unable to walk without aid
      after a year. One trial involving 249 participants compared plasma exchange
      followed by intravenous immunoglobulin with plasma exchange alone, and another
      involving 37 participants compared immunoabsorption followed by intravenous
      immunoglobulin with immunoabsorption alone. Neither revealed significant extra
      benefit from intravenous immunoglobulin. One study of only 39 participants showed
      a trend towards more improvement with high-dose compared with low-dose
      intravenous immunoglobulin. REVIEWER'S CONCLUSIONS: Although there are no
      adequate comparisons with placebo, intravenous immunoglobulin hastens recovery
      from Guillain-Barre syndrome as much as plasma exchange. Giving intravenous
      immunoglobulin after plasma exchange is not significantly better than plasma
      exchange alone. Randomised trials are needed to decide the effect of intravenous
      immunoglobulin in children, in adults with mild disease and in adults who start
      treatment after more than two weeks.

PMID- 14973983
TI  - Corticosteroids for HELLP syndrome in pregnancy.
AB  - BACKGROUND: Hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome
      is a severe form of pre-eclampsia. Pre-eclampsia is a multi-system disease of
      pregnancy associated with an increase in blood pressure and increased perinatal
      and maternal morbidity and mortality. Eighty per cent of women with HELLP
      syndrome present before term. There are suggestions from observational studies
      that steroid treatment in HELLP syndrome may improve disordered maternal
      hematological and biochemical features and perhaps perinatal mortality and
      morbidity. OBJECTIVES: To summarise the evidence on the effects of
      corticosteroids on maternal and neonatal mortality and morbidity in women with
      HELLP syndrome. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group trials register (October 2003). We scanned lists of references
      from review articles and primary studies. SELECTION CRITERIA: Randomised and
      quasi-randomised trials evaluating the effects of adjunctive corticosteroids in
      patients diagnosed with HELLP syndrome were sought. DATA COLLECTION AND ANALYSIS:
      The two authors independently applied inclusion criteria, assessed trial quality
      and extracted relevant data. MAIN RESULTS: Of the five studies reviewed (n =
      170), three were conducted antepartum and two postpartum. Four of the studies
      randomised participants to standard therapy or dexamethasone. One study compared
      dexamethasone with betamethasone. DEXAMETHASONE VERSUS CONTROL: There were no
      significant differences in the primary outcomes of maternal mortality and
      morbidity due to placental abruption, pulmonary oedema and liver hematoma or
      rupture. Of the secondary maternal outcomes, there was a tendency to a greater
      platelet count increase over 48 hours, statistically significantly less mean
      number of hospital stay days (weighted mean difference (WMD) -4.50, 95%
      confidence interval (CI) -7.13 to -1.87), mean interval (hours) to delivery (41
      +/- 15) versus (15 +/- 4.5) (p = 0.0068) in favour of women allocated to
      dexamethasone. There were no significant differences in perinatal mortality or
      morbidity due to respiratory distress syndrome, need for ventilatory support,
      intracerebral hemorrhage, necrotizing enterocolitis and a five minute Apgar less
      than seven. The mean birthweight was significantly greater in the group allocated
      to dexamethasone (WMD 247.00, 95% CI 65.41 to 428.59). DEXAMETHASONE VERSUS
      BETAMETHASONE: There were no significant differences in all the maternal and
      perinatal mortality and in primary morbidity outcomes. Women randomised to
      dexamethasone fared significantly better for: oliguria, mean arterial pressure,
      mean increase in platelet count, mean increase in urinary output and liver enzyme
      elevations. REVIEWER'S CONCLUSIONS: There is insufficient evidence to determine
      whether adjunctive steroid use in HELLP syndrome decreases maternal and perinatal
      mortality, major maternal and perinatal morbidity.

PMID- 14973984
TI  - Corticosteroids for treating severe sepsis and septic shock.
AB  - BACKGROUND: Sepsis may be complicated by impaired corticosteroid production.
      Giving corticosteroids could potentially benefit patients. OBJECTIVES: To examine
      the effects of corticosteroids on death at one month in patients with severe
      sepsis and septic shock. SEARCH STRATEGY: We searched the Cochrane Infectious
      Diseases Group's trial register (August 2003), the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003), MEDLINE (August
      2003), EMBASE (August 2003), LILACS (August 2003), reference lists of articles,
      and also contacted trial authors. SELECTION CRITERIA: Randomized and quasi
      randomized controlled trials of corticosteroids versus placebo or supportive
      treatment in severe sepsis and septic shock. DATA COLLECTION AND ANALYSIS: Two
      pairs of reviewers agreed the eligibility of trials. One reviewer extracted data,
      which was checked by the other reviewers and the primary author of the paper
      whenever possible. We obtained some missing data from the trial authors. We
      assessed trial methodological quality. MAIN RESULTS: We identified 15 trials (n
      =2023). Corticosteroids did not change 28-day all-cause mortality (15 trials, n =
      2022, relative risk (RR) 0.92, 95% confidence interval (CI) 0.75 to 1.14; random
      effects model) and hospital mortality (13 trials, n = 1418, RR 0.89, 95% CI 0.71
      to 1.11; random effects model); however, there was statistically significant
      heterogeneity, with some evidence that this was related to the dosing strategy.
      Corticosteroids reduced intensive care unit mortality (4 trials, n = 425, RR
      0.83, 95% CI 0.70 to 0.97), increased the proportion of shock reversal by day 7
      (6 trials, n = 728, RR 1.22, 95% CI 1.06 to 1.40) and by day 28 (4 trials, n =
      425, RR 1.26, 95% CI 1.04 to 1.52), without increasing the rate of gastroduodenal
      bleeding (10 trials, n = 1321, RR 1.16, 95% CI 0.82 to 1.65), superinfection (12
      trials, n = 1705, RR 0.93, 95% CI 0.73 to 1.18), and of hyperglycaemia (6 trials,
      n = 608, RR 1.22, 0.84 to 1.78). REVIEWER'S CONCLUSIONS: Overall, corticosteroids
      did not change 28-day mortality and hospital mortality in severe sepsis and
      septic shock. Long course of low dose corticosteroids reduced 28-day all-cause
      mortality, and intensive care unit and hospital mortality.

PMID- 14973985
TI  - Retention procedures for stabilising tooth position after treatment with
      orthodontic braces.
AB  - BACKGROUND: Retention is the phase of orthodontic treatment that attempts to keep
      teeth in the corrected positions after orthodontic (dental) braces. Without a
      phase of retention there is a tendency for the teeth to return to their initial
      position (relapse). To prevent relapse almost every patient who has orthodontic
      treatment will require some type of retention. OBJECTIVES: To evaluate the
      effectiveness of different retention strategies used to stabilise tooth position
      after orthodontic braces. SEARCH STRATEGY: The Cochrane Oral Health Group's
      Trials Register, CENTRAL, MEDLINE and EMBASE were searched. Several journals were
      handsearched. No language restrictions were applied. Authors of randomised
      controlled trials (RCTs) were identified and contacted to identify unpublished
      trials. Most recent search: December 2002. SELECTION CRITERIA: RCTs on children
      and adults, who have had retainers fitted or adjunctive procedures undertaken,
      following orthodontic treatment with braces to prevent relapse. The outcomes are:
      how well the teeth are stabilised, survival of retainers, adverse effects on oral
      health and quality of life. DATA COLLECTION AND ANALYSIS: Screening of eligible
      studies, assessment of the methodological quality of the trials and data
      extraction were conducted in duplicate and independently by two reviewers. As no
      two studies compared the same retention strategies (interventions) it was not
      possible to combine the results of any studies. MAIN RESULTS: Four trials
      satisfied the inclusion criteria. These trials all compared different
      interventions: circumferential supracrestal fiberotomy (CSF) combined with full
      time removable retainer versus a full-time removable retainer alone;
      circumferential supracrestal fiberotomy (CSF) combined with a nights-only
      removable retainer versus a nights-only removable retainer alone; removable
      Hawley retainer versus a clear overlay retainer; and three types of fixed
      retainers versus a removable retainer. There was weak unreliable evidence, based
      on data from one trial, that there was a statistically significant increase in
      stability in both the mandibular (p < 0.001) and maxillary anterior segments (p <
      0.001) when the CSF was used, compared with when it was not used. There was also
      weak, unreliable evidence that teeth settle quicker with a Hawley retainer than
      with a clear overlay retainer after 3 months. The quality of the trial reports
      was generally poor. REVIEWER'S CONCLUSIONS: There are insufficient research data
      on which to base our clinical practice on retention at present. There is an
      urgent need for high quality randomised controlled trials in this crucial area of
      orthodontic practice.

PMID- 14973986
TI  - Feverfew for preventing migraine.
AB  - BACKGROUND: Feverfew (Tanacetum parthenium L.) extract is a herbal remedy used
      for preventing attacks of migraine. OBJECTIVES: To systematically review the
      evidence from double-blind randomised controlled trials (RCTs) assessing the
      clinical efficacy and safety of feverfew versus placebo for preventing migraine.
      SEARCH STRATEGY: Publications describing (or which might describe) double-blind
      RCTs of feverfew extract for migraine were sought through the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2003);
      PREMEDLINE/MEDLINE (1966 to July 2003); EMBASE (1974 to July 2003); the trials
      register of the Cochrane Pain, Palliative and Supportive care group (July 2003);
      and AMED (1985 to July 2003). Manufacturers of feverfew were contacted and the
      bibliographies of identified articles checked for further trials. SELECTION
      CRITERIA: Randomised, placebo-controlled, double-blind trials assessing the
      efficacy of feverfew for preventing migraine were included. Trials using clinical
      outcome measures were included. Trials focusing exclusively on physiological
      parameters were excluded. There were no restrictions regarding the language of
      publication. DATA COLLECTION AND ANALYSIS: Data on patients, interventions,
      methods, outcome measures, results and adverse events were extracted
      systematically. Methodological quality was evaluated using the scoring system
      developed by Jadad and colleagues. Two reviewers independently selected studies,
      assessed methodological quality and extracted data. Disagreements concerning
      evaluation of individual trials were resolved through discussion. MAIN RESULTS:
      Five trials (343 patients) met the inclusion criteria. Results from these trials
      were mixed and did not convincingly establish that feverfew is efficacious for
      preventing migraine. Only mild and transient adverse events were reported in the
      included trials. REVIEWER'S CONCLUSIONS: There is insufficient evidence from
      randomised, double-blind trials to suggest an effect of feverfew over and above
      placebo for preventing migraine. It appears from the data reviewed that feverfew
      presents no major safety problems.

PMID- 14973987
TI  - Nitrates for achalasia.
AB  - BACKGROUND: Achalasia is a disease that impairs oesophageal motility. Though
      nitrates have been used to treat achalasia for a long time, the effectiveness of
      nitrates for achalasia is still controversial. OBJECTIVES: To quantify short-term
      and long-term effects of nitrate therapy in patients with achalasia. SEARCH
      STRATEGY: Trials were identified by searching the Cochrane Controlled Trials
      Register (Issue 4-2001), MEDLINE (1966-2001), EMBASE (1980-2001), LILACS - Latin
      American and Caribbean health science literature (1982-2001) and CBM-Chinese
      Biomedical database(1980-2000). Additionally, all references in the identified
      trials were checked for further relevant trials. An updated search was run on the
      Cochrane Library, MEDLINE, and EMBASE in September 2003 - no new trials were
      found. SELECTION CRITERIA: All randomised controlled trials involving achalasic
      patients given any type of nitrates were included. DATA COLLECTION AND ANALYSIS:
      Data were extracted by two independent observers based on the intention to treat
      principle. MAIN RESULTS: Two randomised cross-over studies were found, but no
      results are included. Due to the design of the studies and the method of
      reporting the results in the original paper it was not possible to extract the
      necessary information to examine any of the outcomes. REVIEWER'S CONCLUSIONS: We
      can conclude no implications for practice at this stage. Appropriately designed
      parallel group randomised controlled trials with long term follow-up are needed
      to determine the effects of nitrates.

PMID- 14973988
TI  - Psychological interventions for non-ulcer dyspepsia.
AB  - BACKGROUND: Studies have also shown that NUD patients have higher scores of
      anxiety, depression, neurotism, chronic tension, hostility, hypochondriasis, and
      tendency to be more pessimistic when compared with the community controls.
      However, the role of psychological interventions in NUD remains uncertain.
      OBJECTIVES: This review aims to determine the effectiveness of psychological
      interventions including psychotherapy, psychodrama, cognitive behavioral therapy,
      relaxation therapy and hypnosis in the improvement of either individual or global
      dyspepsia symptom scores and quality of life scores patients with NUD. SEARCH
      STRATEGY: Trials were located through electronic searches of the Cochrane
      Controlled Trials Register (CCTR), MEDLINE, EMBASE, CINAHL and PsycLIT, using
      very broad subject headings and text words. Bibliographies of retrieved articles
      were also searched and experts in the field were contacted. SELECTION CRITERIA:
      All randomised controlled trials (RCTs) or quasi-randomised studies assessing the
      effectiveness of psychological interventions (including psychotherapy,
      psychodrama, cognitive behavioural therapy, relaxation therapy and hypnosis) for
      non-ulcer dyspepsia (NUD) were identified. DATA COLLECTION AND ANALYSIS: Data
      collected included individual, global dyspepsia symptom scores and quality of
      life (QoL) scores. MAIN RESULTS: We identified only four trials, each using
      different psychological interventions and three presenting results in a manner,
      that did not allow synthesis of the data to form a meta-analysis. All trials
      suggest that psychological interventions benefit dyspepsia symptoms and this
      effect persists for one year. However, all trials use statistical techniques that
      adjusted for baseline differences between groups. This should not be necessary
      for a randomised trial that is adequately powered suggesting that the sample size
      of these papers was too small. Unadjusted data was not statistically significant.
      The other problem of psychological intervention include low recruitment and high
      drop out rate which has been shown to be greater in patients receiving group
      therapy. REVIEWER'S CONCLUSIONS: There is currently insufficient evidence from
      this review to confirm the efficacy of psychological intervention in NUD. There
      is also no evidence on the combined effects of pharmacological and psychological
      therapy. Nevertheless, if there are any benefits of psychological therapies, they
      are likely to persist long-term and NUD is a chronic relapsing and remitting
      disorder. Psychological therapies may therefore be offered to patients with
      severe symptoms that have not responded to pharmacological therapies.

PMID- 14973989
TI  - Interventions for tears of the rotator cuff in adults.
AB  - BACKGROUND: Tears of the rotator cuff tendons, which surround the joints of the
      shoulder, are one of the most common causes of pain and disability in the upper
      extremity. OBJECTIVES: To review the efficacy and safety of common interventions
      for tears of the rotator cuff in adults. SEARCH STRATEGY: We searched the
      Cochrane Musculoskeletal Injuries Group specialised trail register (July 2002),
      the Cochrane Controlled Trials Register (The Cochrane Library issue 2, 2002),
      MEDLINE (1966 to December 2001), EMBASE (1974 to December 2001), Biological
      Abstracts (1980 to December 2001), LILACS (1982 to December 2001), CINAHL
      (November 1982 to December 2001), Science Citation Index and reference lists of
      articles. We also contacted authors and handsearched conference proceedings
      focusing on shoulder conditions. SELECTION CRITERIA: Randomised or quasi
      randomised clinical trials involving tears of the rotator cuff were the focus of
      this review. All trials involving conservative interventions or surgery were
      included (non-steroidal anti-inflammatory drugs, intra-articular or subacromial
      glucocorticosteroid injection, oral glucocorticosteroid treatment, physiotherapy,
      and open or arthroscopic surgery). DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed suitability for inclusion, methodological quality and
      extracted data. Dichotomous data were presented as relative risks (RR) and 95%
      confidence intervals (CI), using the fixed effects model. MAIN RESULTS: Eight
      trials involving 455 people were included and 393 patients analysed. Trials were
      grouped in eight categories of conservative or surgical treatment. The median
      quality score of all trials combined was 16 out of a possible 24 points, with a
      range of 12-18. In general, included trials differed on diagnostic criteria for
      rotator cuff tear, there was no uniformity in reported outcome measures, and data
      which could be summarised were rarely reported. Only results from two studies
      comparing open repair to arthroscopic debridement could be pooled. There is weak
      evidence for the superiority of open repair of rotator cuff tears compared with
      arthroscopic debridement. REVIEWER'S CONCLUSIONS: There is little evidence to
      support or refute the efficacy of common interventions for tears of rotator cuff
      in adults. As well as the need for further well designed clinical trials, uniform
      methods of defining interventions for rotator cuff tears and validated outcome
      measures are also essential.

PMID- 14973990
TI  - Stabilisation splint therapy for temporomandibular pain dysfunction syndrome.
AB  - BACKGROUND: Pain dysfunction syndrome (PDS) is the most common temporomandibular
      disorder (TMD). There are many synonyms for this condition including facial
      arthromylagia, TMJ dysfunction syndrome, myofacial pain dysfunction syndrome,
      craniomandibular dysfunction and myofacial pain dysfunction. The aetiology of PDS
      is multifactorial and many different therapies have been advocated. OBJECTIVES:
      To establish the effectiveness of stabilisation splint therapy in reducing
      symptoms in patients with pain dysfunction syndrome. SEARCH STRATEGY: Electronic
      databases (including the Cochrane Oral Health Group's Trials Register; the
      Cochrane Central Register of Controlled Trials (CENTRAL); The Cochrane Library
      Issue 2, 2003; MEDLINE (1966 to June 2001); EMBASE (1966 to June 2001)) were
      searched. Handsearching of relevant journals was undertaken and reference lists
      of included studies screened. Experts in the field were contacted to identify
      unpublished articles. There was no language restriction. SELECTION CRITERIA:
      Randomised or quasi-randomised controlled trials (RCTs), in which splint therapy
      was compared concurrently to no treatment, other occlusal appliances, or any
      other active intervention. DATA COLLECTION AND ANALYSIS: Data extraction was
      carried out independently and in duplicate. Validity assessment of the included
      trials was carried out at the same time as data extraction. Discrepancies were
      discussed and a third reviewer consulted. The author of the primary study was
      contacted where necessary. The studies were grouped according to treatment type
      and duration of follow up. MAIN RESULTS: Twenty potentially relevant RCTs were
      identified. Eight trials were excluded leaving 12 RCTs for analysis.
      Stabilisation splint therapy was compared to: acupuncture, bite plates,
      biofeedback/stress management, visual feedback, relaxation, jaw exercises, non
      occluding appliance and minimal/no treatment. There was no evidence of a
      statistically significant difference in the effectiveness of stabilisation splint
      therapy (SS) in reducing symptoms in patients with pain dysfunction syndrome
      compared with other active treatments. There is weak evidence to suggest that the
      use of SS for the treatment of PDS may be beneficial for reducing pain severity,
      at rest and on palpation, when compared to no treatment. REVIEWER'S CONCLUSIONS:
      There is insufficient evidence either for or against the use of stabilisation
      splint therapy for the treatment of temporomandibular pain dysfunction syndrome.
      This review suggests the need for further, well conducted RCTs that pay attention
      to method of allocation, outcome assessment, large sample size, and enough
      duration of follow up. A standardisation of the outcomes of the treatment of PDS
      should be established in the RCTs.

PMID- 14973991
TI  - One topical fluoride (toothpastes, or mouthrinses, or gels, or varnishes) versus
      another for preventing dental caries in children and adolescents.
AB  - BACKGROUND: Topical fluorides in the form of toothpaste, mouthrinse, varnish and
      gel are effective caries preventive measures. However, there is uncertainty about
      the relative value of these interventions. OBJECTIVES: To compare the
      effectiveness of one form of topical fluoride intervention with another when used
      for the prevention of dental caries in children. SEARCH STRATEGY: We searched the
      Cochrane Oral Health Group's Trials Register (May 2000), the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2000),
      MEDLINE (1966 to January 2000), plus several other databases. We handsearched
      journals, reference lists of articles and contacted selected authors and
      manufacturers. SELECTION CRITERIA: Randomized or quasi-randomized controlled
      trials with blind outcome assessment, comparing fluoride varnish, gel,
      mouthrinse, or toothpaste with each other in children up to 16 years during at
      least 1 year. The main outcome was caries increment measured by the change in
      decayed, missing and filled tooth surfaces (D(M)FS). DATA COLLECTION AND
      ANALYSIS: Inclusion decisions, quality assessment and data extraction were
      duplicated in a random sample of one third of studies, and consensus achieved by
      discussion or a third party. Authors were contacted for missing data. The primary
      measure of effect was the prevented fraction (PF) that is the difference in mean
      caries increments between the 'experimental' and 'control' groups expressed as a
      percentage of the mean increment in the control group. Random effects meta
      analyses were performed where data could be pooled. MAIN RESULTS: There were 17
      studies included, and 15 contributed data for the meta-analyses. Fluoride
      toothpaste was not significantly different from mouthrinse (pooled DMFS PF 0%;
      95% CI, -18% to 19%; p = 0.94), or gel (pooled DMFS PF 0%; 95% CI, -21% to 21%; p
      = 1), or both gel and mouthrinse (pooled DMFS PF 1%; 95% CI, -13% to 14%; p =
      0.94); heterogeneity was substantial. Results from the single trial comparing
      toothpaste with varnish (in deciduous teeth) were inconclusive (dfs PF 5%; CI not
      obtainable). The pooled results from the comparisons of fluoride varnish with
      mouthrinse was a non-significant difference favouring varnish (DMFS PF 10%; 95%
      CI, -12% to 32%; p = 0.40), but this result was not robust to sensitivity
      analysis performed, and heterogeneity was considerable. Results from the single
      trial comparing varnish with gel (14%, 95% CI, -12% to 40%; p = 0.30) and the
      single trial comparing gel with mouthrinse (-14% DMFS PF; 95% CI, -40% to 12%; p
      = 0.30) were inconclusive (favoured varnish and mouthrinse respectively).
      REVIEWER'S CONCLUSIONS: Fluoride toothpastes in comparison to mouthrinses or gels
      appear to have a similar degree of effectiveness for the prevention of dental
      caries in children. There is no clear suggestion that fluoride varnish is more
      effective than mouthrinses and the evidence for the comparative effectiveness of
      fluoride varnishes and gels, and mouthrinses and gels is inconclusive. No
      conclusions about adverse effects could be reached, because no data were reported
      on in the trials. Acceptance is likely to be greater for fluoride toothpaste.

PMID- 14973992
TI  - Combinations of topical fluoride (toothpastes, mouthrinses, gels, varnishes)
      versus single topical fluoride for preventing dental caries in children and
      adolescents.
AB  - BACKGROUND: Topical fluoride therapy (TFT) in the form of toothpastes,
      mouthrinses, varnishes and gels are effective caries preventive measures.
      However, there is uncertainty about the relative value of these interventions
      when used together. OBJECTIVES: To compare the effectiveness of two TFT
      modalities combined with one of them alone (mainly toothpaste) when used for the
      prevention of dental caries in children. SEARCH STRATEGY: We searched the
      Cochrane Oral Health Group's Trials Register (May 2000), the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2000),
      MEDLINE (1966 to January 2000), plus several other databases. We handsearched
      journals, reference lists of articles and contacted selected authors and
      manufacturers. SELECTION CRITERIA: Randomized or quasi-randomized controlled
      trials with blind outcome assessment, comparing fluoride varnish, gel,
      mouthrinse, or toothpaste in combination with each other in children up to 16
      years during at least 1 year. The main outcome was caries increment measured by
      the change in decayed, missing and filled tooth surfaces (D(M)FS). DATA
      COLLECTION AND ANALYSIS: Inclusion decisions, quality assessment and data
      extraction were duplicated in a random sample of one third of studies, and
      consensus achieved by discussion or a third party. Authors were contacted for
      missing data. The primary measure of effect was the prevented fraction (PF) that
      is the difference in mean caries increments between the 'treatment' and 'control'
      groups expressed as a percentage of the mean increment in the control group.
      Random effects meta-analyses were performed where data could be pooled. MAIN
      RESULTS: Eleven of the 12 included studies contributed data for the meta
      analyses. For the nine trials that provided data for the main meta-analysis on
      the effect of fluoride mouthrinses, gels or varnishes used in combination with
      toothpaste (involving 4026 children) the D(M)FS pooled PF was 10% (95% CI, 2% to
      17%; p = 0.01) in favour of the combined regimens. Heterogeneity was not
      substantial in these results (I square = 32%). The separate meta-analyses of
      fluoride gel or mouthrinse combined with toothpaste versus toothpaste alone
      favour the combined regimens, but differences were not statistically significant;
      the significant difference in favour of the combined use of fluoride varnish and
      toothpaste accrues from a very small trial and appears likely to be a spurious
      result. Not all other combinations of possible practical value were tested in the
      included studies. The only other statistically significant result was in favour
      of the combined use of fluoride gel and mouthrinse in comparison to gel alone
      (pooled DMFS PF 23%; 95% CI, 4% to 43%; p = 0.02), based on two trials. No other
      combinations of TFT were consistently superior to a single TFT. REVIEWER'S
      CONCLUSIONS: Topical fluorides (mouthrinses, gels, or varnishes) used in addition
      to fluoride toothpaste achieve a modest reduction in caries compared to
      toothpaste used alone. No conclusions about any adverse effects could be reached,
      because data were scarcely reported in the trials.

PMID- 14973993
TI  - Timed voiding for the management of urinary incontinence in adults.
AB  - BACKGROUND: Timed voiding is a fixed time interval toileting assistance program
      that has been promoted for the management of people with urinary incontinence who
      cannot participate in independent toileting. For this reason, it is commonly
      assumed to represent current practice in residential aged care settings.
      OBJECTIVES: To assess the effects of timed voiding for the management of urinary
      incontinence in adults who cannot participate in independent toileting. SEARCH
      STRATEGY: We searched the Cochrane Incontinence Group specialised register (9 May
      2002), MEDLINE (January 1966 to December 2002), EMBASE (January 1980 to Week 18
      2002), CINAHL (January 1982 to February 2001), PsycINFO (January 1972 to
      current), Biological Abstracts (January 1980 to December 2000), Current Contents
      (January 1993 to December 2001) and the reference lists of relevant articles. We
      also contacted experts in the field, searched relevant websites and handsearched
      journals and conference proceedings. SELECTION CRITERIA: We selected all
      randomised and quasi-randomised trials that addressed timed voiding in an adult
      population and that had an alteration in continence status as a primary outcome.
      We included those trials that had assessed timed voiding delivered either alone
      or in combination with another intervention and compared it with either usual
      care, or no timed voiding, or another intervention. DATA COLLECTION AND ANALYSIS:
      Data extraction and quality assessment were undertaken by at least two people
      working independently of each other. Any differences were resolved by discussion
      until agreement was reached. The relative risk for dichotomous data were
      calculated with 95% confidence intervals. Where data were insufficient to support
      a quantitative analysis, a narrative overview was undertaken. MAIN RESULTS: Two
      trials with a total of 298 participants met the inclusion criteria. Both compared
      timed voiding plus additional intervention with usual care. In one of these timed
      voiding was combined with continence products, placement of a bedside commode for
      each participant, education to staff on transfer techniques, feedback and
      encouragement to staff, praise to participants for "successful responses" and
      administration of oxybutynin in small doses. The mean percentage who were
      incontinent when checked daily was 20% in the intervention group compared with
      80% in the control group. No further between group analysis was possible from the
      data reported. The other trial combined timed voiding with a medical assessment
      and individualised medical management that was based on clinical data. Reduction
      in the number of participants with daytime and night-time incontinence was
      greater in the intervention group but this difference was statistically
      significant only for night-time wetting. There was no difference in the volume of
      urine lost as determined by pad weighing. The methodological quality of these
      trials was not high based on the quality appraisal criteria of the Cochrane
      Incontinence Group. In particular, there was a lack of clarity regarding levels
      of blinding. It was not possible to combine data from trials. In both trials, the
      fixed schedule of toileting was combined with other interventions. The extent to
      which the results reflect the contribution of timed voiding is unknown because
      the trials' design did not allow assessment of the effects of the fixed schedule
      of toileting separately from other components of the interventions. REVIEWER'S
      CONCLUSIONS: The data were too few and of insufficient quality to provide
      empirical support for or against the intervention of timed voiding.

PMID- 14973994
TI  - Rotavirus vaccine for preventing diarrhoea.
AB  - BACKGROUND: Rotaviruses cause viral gastroenteritis and result in more deaths
      from diarrhoea in children under 5 years of age than any other single agent,
      particularly in low- and middle-income countries. OBJECTIVES: To assess rotavirus
      vaccines in relation to preventing rotavirus diarrhoea, death, and adverse
      events. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group's
      trial register (October 2003), the Cochrane Central Register of Controlled Trials
      (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to October 2003), EMBASE
      (January 1980 to October 2003), LILACS (1982 to October 2003), Biological
      Abstracts (January 1982 to October 2003), reference lists of articles, and
      contacted researchers and rotavirus vaccine manufacturers. SELECTION CRITERIA:
      Randomized controlled trials comparing rotavirus vaccines to placebo, no
      intervention, or other rotavirus vaccines in children and adults. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently extracted data and assessed trial
      methodological quality, and contacted trial authors for additional information.
      MAIN RESULTS: Sixty-four trials provided information on efficacy and safety of
      three main types of rotavirus vaccine (bovine, human, and rhesus) for 21,070
      children. Different levels of efficacy were demonstrated with different vaccines
      varying from 22 to 89% to prevent one episode of rotavirus diarrhoea, 11 to 44%
      to prevent one episode of all-cause diarrhoea, and 43 to 90% to prevent one
      episode of severe rotavirus diarrhoea. Rhesus vaccine demonstrated a similar
      efficacy against one episode of rotavirus diarrhoea (37 and 44% respectively),
      and one episode of all-cause diarrhoea (around 15%) for trials performed in high
      and middle-income countries. Results on mortality and safety of the vaccines were
      scarce and incomplete. We noticed important heterogeneity among the pooled
      studies and were unable to discard a biased estimation of effect. REVIEWER'S
      CONCLUSIONS: Current evidence shows that rhesus rotavirus vaccines (particularly
      RRV-TV) and the human rotavirus vaccine 89-12 are efficacious in preventing
      diarrhoea caused by rotavirus and all-cause diarrhoea. Evidence about safety, and
      about mortality or prevention of severe outcomes, is scarce and inconclusive.
      Bovine rotavirus vaccines were also efficacious, but safety data are not
      available. Trials of new rotavirus vaccines will hopefully improve the evidence
      base. Randomized controlled trials should be performed simultaneously in high-,
      middle-, and low-income countries.

PMID- 14973995
TI  - Medical methods for first trimester abortion.
AB  - BACKGROUND: Surgical abortion up to 63 days by vacuum aspiration or dilatation
      and curettage has been the method of choice since the 1960s. Medical abortion
      became an alternative method of first trimester pregnancy termination with the
      availability of prostaglandins in the early 1970s and anti-progesterones in the
      1980s. The most widely researched drugs are prostaglandins (PGs) alone,
      mifepristone alone, methotrexate alone, mifepristone with prostaglandins and
      methotrexate with prostaglandins. OBJECTIVES: To compare different medical
      methods for first trimester abortion. SEARCH STRATEGY: The Cochrane Controlled
      Trials Register, MEDLINE and Popline were systematically searched. Reference
      lists of retrieved papers were also searched. Experts in WHO/HRP were contacted.
      SELECTION CRITERIA: Types of studies. Randomised controlled trials comparing
      different medical methods (e.g. single drug, combination), ways of application,
      or different dose regimens, single or combined, for medical abortion, were
      considered. Trials were assessed and included if they had adequate concealment of
      allocation, randomisation procedure and follow-up. Women, pregnant in the first
      trimester, undergoing medical abortion were the participants. Different medical
      methods used for first trimester abortion, compared with each other or placebo
      were included. The outcomes sought include mortality, failure to achieve complete
      abortion, surgical evacuation (as emergency procedure, non-emergency procedure,
      or undefined), ongoing pregnancy at follow-up, time until passing of conceptus (>
      3-6 hours), blood transfusion, blood loss (measured or clinically relevant drop
      in haemoglobin), days of bleeding, pain resulting from the procedure (reported by
      the women or measured by use of analgesics), additional uterotonics used, women's
      dissatisfaction with the procedure, nausea, vomiting, diarrhoea. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently selected trials for inclusion from the
      results of the search strategy described previously. The selection of trials for
      inclusion in the review was performed independently by two reviewers after
      employing the search strategy described previously. Trials under consideration
      were evaluated for appropriateness for inclusion and methodological quality
      without consideration of their results. A form was designed to facilitate the
      data extraction. Data were processed using Revman software. MAIN RESULTS: Thirty
      nine trials were included in the review. The effectiveness outcomes below refer
      to 'failure to achieve complete abortion' with the intended method unless
      otherwise stated. 1) Combined regimen mifepristone/prostaglandin: Mifepristone
      600 mg compared to 200 mg shows similar effectiveness in achieving complete
      abortion (4 trials, RR 1.07, 95% CI 0.87 to 1.32). Misoprostol administered
      orally is less effective (more failures) than the vaginal route (RR 3.00, 95% CI
      1.44 to 6.24) and may be associated with more frequent side effects such as
      nausea and diarrhoea. 2) Mifepristone alone is less effective compared to the
      combined regimen mifepristone/prostaglandin (RR 3.76 95% CI 2.30 to 6.15). 3)
      Similarly, the 5 trials included in the comparison of prostaglandin compared to
      the combined regimen reported in all but one higher effectiveness with the
      combined regime compared to prostaglandin. The results of these studies were not
      pooled but the RR of failure with prostaglandin alone is between 1.4 to 3.75 and
      the 95% confidence intervals indicate statistical significance. 4) In one trial
      comparing gemeprost 0.5 mg with misoprostol 800 mcg, misoprostol was more
      effective (failure with gemeprost: RR 2.86, 95% CI 1.14 to 7.18). 5) There was no
      difference when using split dose compared to single dose of prostaglandin. 6)
      Combined regimen methotrexate/prostaglandin: there was no statistically
      significant difference in failure to achieve complete abortion comparing
      methotrexate administered intramuscular to oral (RR 2.04, 95% CI 0.51 to 8.07).
      Similarly, early (day 3) vs late (day 5) administration of prostaglandin showed
      no significant of prostaglandin showed no significant difference (RR 0.72, 95% CI
      0.36 to 1.43). One trial compared the effect of tamoxifen vs methotrexate and no
      statistically significant differences were observed in effectiveness between the
      groups. REVIEWER'S CONCLUSIONS: Safe and effective medical abortion methods are
      available. Combined regimens are more effective than single agents. In the
      combined regimen, the dose of mifepristone can be lowered to 200 mg without
      significantly decreasing the method effectiveness. Misoprostol vaginally is more
      effective than orally. Some of the results are based on small studies only and
      therefore carry some uncertainty. Almost all trials were conducted in hospital
      settings with good access to support and emergency services. It is therefore not
      clear if the results are readily applicable to under-resourced settings where
      such services are lacking even if the agents used are available.

PMID- 14973996
TI  - Acupuncture for Bell's palsy.
AB  - BACKGROUND: Bell's palsy or idiopathic facial palsy is an acute facial paralysis
      due to inflammation of the facial nerve. A number of studies published in China
      have suggested acupuncture is beneficial for facial palsy. OBJECTIVES: The
      objective of this review was to examine the efficacy of acupuncture in hastening
      recovery and reducing long-term morbidity from Bell's palsy. SEARCH STRATEGY: We
      searched the Cochrane Neuromuscular Disease Group Register, MEDLINE (January 1966
      to December 2002), EMBASE (January 1980 to December 2002), LILACS (from January
      1982 to December 2002) and the Chinese Biomedical Retrieval System (January 1978
      to December 2002) for randomised controlled trials using 'Bell's palsy' and its
      synonyms, 'idiopathic facial paralysis' or 'facial palsy' as well as search terms
      including 'acupuncture'. Chinese journals in which we thought we might find
      randomised controlled trials or controlled clinical trials relevant to our study
      were handsearched. We reviewed the bibliographies of the randomised trials and
      contacted the authors and known experts in the field to identify additional
      published or unpublished data. SELECTION CRITERIA: We included all randomised or
      quasi-randomised controlled trials involving acupuncture in the treatment of
      Bell's palsy irrespective of any language restrictions. DATA COLLECTION AND
      ANALYSIS: Two reviewers identified potential articles from the literature search
      and extracted data independently using a data extraction form. The assessment of
      methodological quality included allocation concealment, patient blinding,
      differences at baseline of the experimental groups and completeness of follow-up.
      Two reviewers assessed quality independently. All disagreements were resolved by
      discussion between the reviewers. MAIN RESULTS: Three studies including a total
      of 238 patients met the inclusion criteria. Two of them used acupuncture while
      the third used acupuncture combined with drugs. No trials reported on the
      outcomes specified for this review. Three included studies showed that the
      therapeutic effect of acupuncture alone was superior to that of medication or
      that acupuncture combined with medication was better than medication alone.
      Harmful side-effects were not reported in any of the trials. Flaws in study
      design or reporting (particularly uncertain allocation concealment and
      substantial loss to follow-up) and clinical differences between trials prevented
      a meta-analysis. REVIEWER'S CONCLUSIONS: The quality of the included trials was
      inadequate to allow any conclusion about the efficacy of acupuncture. More
      research with high quality trials is needed.

PMID- 14973997
TI  - Pleurodesis for malignant pleural effusions.
AB  - BACKGROUND: Approximately half of all patients with metastatic cancer develop a
      malignant pleural effusion which is likely to lead to a significant reduction in
      quality of life secondary to symptoms such as dyspnoea and cough. The aim of
      pleurodesis in these patients is to prevent re-accumulation of the effusion and
      thereby of symptoms, and avoid the need for repeated hospitalization for
      thoracocentesis. Numerous clinical studies have been performed to try to
      determine the optimal pleurodesis strategy, and synthesis of the available
      evidence should facilitate this. OBJECTIVES: The aims of this review were to
      ascertain the optimal technique of pleurodesis in cases of malignant pleural
      effusion; to confirm the need for a sclerosant; and to clarify which, if any, of
      the sclerosants is the most effective. SEARCH STRATEGY: The Cochrane Central
      Register of Controlled Trials was searched for studies on 'pleurodesis'. Studies
      for inclusion were also identified from MEDLINE (1980 to June 2002) and EMBASE
      (1980 to May 2002). No language restriction was applied. SELECTION CRITERIA: RCTs
      of adults subjects undergoing pleurodesis for pleural effusion in the context of
      metastatic malignancy (or a malignant process leading to pleural effusion) were
      included. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected
      studies for inclusion in the review, and extracted data using a standard data
      collection form. Primary outcome measures sought were effectiveness of
      pleurodesis as defined by freedom from recurrence of effusions, and mortality
      after pleurodesis. Secondary outcomes were adverse events due to pleurodesis.
      Dichotomous data were meta-analysed using a fixed effect model and expressed as
      relative risk. The number-needed-to-treat (NNT) was calculated for pleurodesis
      efficacy. In addition, for adverse events, the overall percentage of patients
      across studies exhibiting a particular adverse effect such as fever, pain, or
      gastrointestinal symptoms was calculated. MAIN RESULTS: A total of 36 RCTs with
      1499 subjects were eligible for meta-analysis. The use of sclerosants
      (mitozantrone, talc and tetracycline combined)compared with control (instillation
      of isotonic saline or equivalent pH isotonic saline or tube drainage alone) was
      associated with an increased efficacy of pleurodesis. The relative risk (RR) of
      non-recurrence of an effusion is 1.20 (95% CI 1.04 to 1.38) in favour of the use
      of sclerosants based on five studies with a total 228 subjects. Comparing
      different sclerosants, talc was found to be the most efficacious. The RR of
      effusion non-recurrence was 1.34 (95% CI 1.16 to 1.55) in favour of talc compared
      with bleomycin, tetracycline, mustine or tube drainage alone based on 10 studies
      comprising 308 subjects. This was not associated with increased mortality post
      pleurodesis. The RR of death was 1.19 (95% CI 0.08 to 1.77) for talc compared to
      bleomycin, tetracycline, mustine and tube drainage alone based on six studies of
      186 subjects. Death was not reported in all studies and, when reported, was
      attributed to underlying disease, only one death being reported as procedure
      related. In the comparison of thoracoscopic versus medical pleurodesis,
      thoracoscopic pleurodesis was found to be more effective. The RR of non
      recurrence of effusion is 1.19 (95% CI 1.04 to 1.36) in favour of thoracoscopic
      pleurodesis compared with tube thoracostamy pleurodesis utilizing talc as
      sclerosant based on two studies with 112 subjects. Comparing thoracoscopic versus
      bedside instillation (with different sized chest tubes) of various sclerosants
      (tetracycline, bleomycin, talc or mustine) the RR of non-recurrence of effusion
      is 1.68 (95% CI 1.35 to 2.10) based on five studies with a total of 145
      participants.Adverse events were not reported adequately to enable meta-analysis.
      REVIEWER'S CONCLUSIONS: The available evidence supports the need for chemical
      sclerosants for successful pleurodesis, the use of talc as the sclerosant of
      choice, and thoracoscopic pleurodesis as the preferred technique for pleurodesis
      based on efficacy. There was no evidence for an increase in mortality following
      talc pleurodesis.

PMID- 14973998
TI  - Treatment for lupus nephritis.
AB  - BACKGROUND: Lupus nephritis is the renal manifestation of systemic lupus
      erythematosus (SLE) - a disease mainly affecting young women with substantial
      morbidity and mortality. It is classified by the World Health Organization (WHO)
      criteria I - VI based on histology. WHO Class IV is a diffuse proliferative
      glomerulonephritis which has the worst prognosis without treatment, with a
      reported 17% five year survival in the era 1953-1969. This survival was 82% in
      the early 1990's and continues to improve. An important factor behind this has
      been the use of cytotoxics such as cyclophosphamide in addition to steroids.
      OBJECTIVES: To assess the benefits and harms of different treatments in biopsy
      proven proliferative lupus nephritis (LN). SEARCH STRATEGY: We searched the
      Cochrane Renal Group's specialised register (January 2003), the Cochrane Central
      Register of Randomised Controlled Trials (CENTRAL - The Cochrane Library issue 1,
      2003), MEDLINE (1966 - 31 January 2003), EMBASE (1980 - 31 January 2003) and
      handsearched reference lists of retrieved articles. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) and quasi-RCTs comparing treatments for PLN
      in both adult and paediatric patients with Class III, IV, Vc, Vd lupus nephritis
      were included. All treatments were considered. DATA COLLECTION AND ANALYSIS: Data
      was extracted and quality assessed independently by two reviewers, with
      differences resolved by discussion. Dichotomous outcomes are reported as relative
      risk (RR) and measurements on continuous scales are reported as weighted mean
      differences (WMD) with 95% confidence intervals. Subgroup analysis by study
      quality, drug type and drug route have been performed where possible to explore
      reasons for heterogeneity. MAIN RESULTS: Of 920 articles identified, 25 were RCTs
      suitable for inclusion, which enrolled 915 patients. The majority compared
      cyclophosphamide or azathioprine plus steroids versus steroids alone.
      Cyclophosphamide plus steroids reduced the risk of doubling of serum creatinine
      (RR 0.59, 95% CI 0.40 to 0.88) compared to steroids alone but had no impact on
      mortality (RR 0.98, 95% CI 0.53 to 1.82). The risk of ovarian failure was
      significantly increased (RR 2.18, 95% CI 1.10 to 4.34). Azathioprine plus
      steroids reduced the risk of all cause mortality compared to steroids alone (RR
      0.60, 95% CI 0.36 to 0.99), but did not alter renal outcomes. Neither therapy was
      associated with increased risk of major infection. No benefit was found with
      addition of plasma exchange to cyclophosphamide or azathioprine plus steroids for
      mortality ( RR 0.71, 95% CI 0.50 to 1.02), doubling of serum creatinine (RR 0.17,
      95% CI 0.02 to 1.26) or end-stage renal failure (RR 1.24, 95% CI 0.60 to 2.57).
      There was also no increased risk of major infection (RR 0.69, 95% CI 0.35 to
      1.37). REVIEWER'S CONCLUSIONS: Until future RCTs of newer agents are completed,
      the current use of cyclophosphamide combined with steroids remains the best
      option to preserve renal function in proliferative LN. The smallest effective
      dose and shortest duration of treatment should be used to minimise gonadal
      toxicity, without compromising efficacy.

PMID- 14973999
TI  - Acupuncture for induction of labour.
AB  - BACKGROUND: This is one of a series of reviews of methods of cervical ripening
      and labour induction using standardised methodology. The use of complementary
      therapies is increasing and some women look to complementary therapies during
      pregnancy and childbirth to be used alongside conventional medical practice.
      Acupuncture involves the insertion of very fine needles into specific points of
      the body. The limited observational studies to date suggest acupuncture for
      induction of labour appears safe, has no known teratogenic effects, and may be
      effective. The evidence regarding the clinical effectiveness of this technique is
      limited. OBJECTIVES: To determine the effects of acupuncture for third trimester
      cervical ripening or induction of labour. SEARCH STRATEGY: The Cochrane Pregnancy
      and Childbirth Group trials register (February 2003), the Cochrane Central
      Register of Controlled Trials (The Cochrane Library, Issue 1, 2003), PubMed (1966
      to present), CISCOM (1960 to present), EMBASE (1980 to present) and
      bibliographies of relevant papers. SELECTION CRITERIA: Clinical trials comparing
      acupuncture used for third trimester cervical ripening or labour induction with
      placebo/no treatment or other methods listed above it on a predefined list of
      labour induction methods. DATA COLLECTION AND ANALYSIS: A strategy was developed
      to deal with the large volume and complexity of trial data relating to labour
      induction. This involved a two-stage method of data extraction. MAIN RESULTS: One
      trial of 56 women was included in the review. Data were not in a form that could
      be included in the meta-analysis. REVIEWER'S CONCLUSIONS: There is a need for
      well-designed randomised controlled trials to evaluate the role of acupuncture to
      induce labour and for trials to assess clinically meaningful outcomes.

PMID- 14974000
TI  - Psychotherapeutic interventions for adults with asthma.
AB  - BACKGROUND: Many people have asthma, and for some their symptoms may be triggered
      by psychological factors. In addition compliance with medical therapy may have a
      psychological dimension. Therefore, psychological interventions aim to reduce the
      burden of symptoms and improve management of the disease. OBJECTIVES: To assess
      the effectiveness of psychological interventions for adults with asthma. SEARCH
      STRATEGY: The Cochrane Airways Group specialised register and PsycINFO were
      searched with pre-defined terms until September 2003. SELECTION CRITERIA:
      Randomised controlled trials published in any language assessing the effects of a
      psychological intervention compared with a form of control in adult participants
      were included in the review. DATA COLLECTION AND ANALYSIS: Two reviewers assessed
      the relevance of abstracts identified by electronic searching and retrieved
      agreed studies for further scrutiny. The studies that met the inclusion criteria
      were assembled and data extracted. MAIN RESULTS: Twelve studies were included in
      the review, however study quality was poor and sample sizes were frequently
      small. No meta-analysis could be performed due to the diversity of interventions
      and the outcomes assessed. Findings between studies were conflicting. This may
      have been due to the different types of interventions used and the deficiencies
      in trial design. REVIEWER'S CONCLUSIONS: This review was unable to draw firm
      conclusions for the role of psychological interventions in asthma due to the
      absence of an adequate evidence base. Large, well-conducted and reported
      randomised trials are required in this area, in order to determine the effects of
      these techniques in the treatment of asthma in adults.

PMID- 14974001
TI  - Perioperative fluid volume optimization following proximal femoral fracture.
AB  - BACKGROUND: Proximal Femoral Fracture (PFF) or 'hip fracture' is a frequent
      injury, and adverse outcomes are common. Several factors suggest the importance
      of developing techniques to optimize intravascular fluid volume. These may
      include protocols that enhance the efficacy of clinicians' assessments, invasive
      techniques such as oesophageal Doppler or central venous pressure monitoring, or
      advanced non-invasive techniques such as plethysmographic pulse volume
      determination. OBJECTIVES: To determine the optimal method of fluid volume
      optimization for adult patients undergoing surgical repair of PFF. Comparisons of
      fluid types, of blood transfusion strategies or of pharmacological interventions
      are not considered in this review. SEARCH STRATEGY: We searched CENTRAL (The
      Cochrane Library, issue 4, 2003), MEDLINE (1985 to 2003), EMBASE (1985 to 2003),
      and bibliographies of retrieved articles. Relevant journals and conference
      proceedings were handsearched. SELECTION CRITERIA: Randomized controlled studies
      comparing a fluid optimization intervention with normal practice or with another
      fluid optimization intervention, in patients following PFF undergoing surgery of
      any type under anaesthesia of any type. DATA COLLECTION AND ANALYSIS: Searches
      and exclusion of clearly irrelevant articles were performed by one reviewer. Two
      reviewers examined independently the remaining studies, extracting study quality
      and results data. A wide range of short- and long-term outcome data were sought.
      Studies were excluded if they did not meet selection criteria or if results were
      likely to be biased. Due to inconsistent data reporting, combination of data was
      not generally possible. MAIN RESULTS: Searches identified four trials, of which
      two studies, randomizing a total of 130 patients, were of adequate quality and
      addressed the review question. Both studies were of invasive advanced
      haemodynamic monitoring, either oesophageal Doppler ultrasonography or central
      venous pressure monitoring, during the intraoperative period only. In both,
      invasive monitoring led to significant increases in fluid volumes infused and
      reductions in length of hospital stay. The pooled Peto odds ratio for in-hospital
      fatality was 1.44 (95% confidence interval 0.45-4.62). Neither study followed
      patients beyond hospital discharge or assessed functional outcomes. No serious
      complications were directly attributable to the interventions. There were no
      studies of protocol-guided fluid optimization or of advanced non-invasive
      techniques. REVIEWER'S CONCLUSIONS: Invasive methods of fluid optimization during
      surgery may shorten hospital stay, but their effects on other important, patient
      centred, longer-term outcomes are uncertain. Adverse effects on fatality cannot
      be excluded. Other fluid optimization techniques have not been evaluated. The
      lack of randomized studies of adequate quality addressing this important question
      is disappointing. More research is needed.

PMID- 14974002
TI  - Active placebos versus antidepressants for depression.
AB  - BACKGROUND: Although there is a consensus that antidepressants are effective in
      depression, placebo effects are also thought to be substantial. Side effects of
      antidepressants may reveal the identity of medication to participants or
      investigators and thus may bias the results of conventional trials using inert
      placebos. Using an 'active' placebo which mimics some of the side effects of
      antidepressants may help to counteract this potential bias. OBJECTIVES: To
      investigate the efficacy of antidepressants when compared with 'active' placebos.
      SEARCH STRATEGY: The Cochrane Collaboration Depression, Anxiety and Neurosis
      review groups's search strategy was used to search MEDLINE (1966-2000), PsychLIT
      (1980-2000) and EMBASE (1974-2000) and this was last done in July 2000. Reference
      lists from relevant articles and textbooks were searched and 12 specialist
      journals were handsearched up to 1996. SELECTION CRITERIA: Randomised and quasi
      randomised controlled trials comparing antidepressants with active placebos in
      people with depression. DATA COLLECTION AND ANALYSIS: Since many different
      outcome measures were used a standard measure of effect was calculated for each
      trial. A subgroup analysis of inpatient and outpatient trials was conducted. Two
      reviewers independently assessed whether each trial met inclusion criteria. MAIN
      RESULTS: Nine studies involving 751 participants were included. Two of them
      produced effect sizes which showed a consistent and statistically significant
      difference in favour of the active drug. Combining all studies produced a pooled
      estimate of effect of 0.39 standard deviations (confidence interval, 0.24 to
      0.54) in favour of the antidepressant measured by improvement in mood. There was
      high heterogeneity due to one strongly positive trial. Sensitivity analysis
      omitting this trial reduced the pooled effect to 0.17 (0.00 to 0.34). The pooled
      effect for inpatient and outpatient trials was highly sensitive to decisions
      about which combination of data was included but inpatient trials produced the
      lowest effects. REVIEWER'S CONCLUSIONS: The more conservative estimates from the
      present analysis found that differences between antidepressants and active
      placebos were small. This suggests that unblinding effects may inflate the
      efficacy of antidepressants in trials using inert placebos. Further research into
      unblinding is warranted.

PMID- 14974003
TI  - Smoking cessation for the secondary prevention of coronary heart disease.
AB  - BACKGROUND: Although the importance of smoking as a risk factor for coronary
      heart disease is beyond doubt, the speed and magnitude of risk reduction when a
      smoker with coronary heart disease quits are still subjects of debate.
      OBJECTIVES: To estimate the magnitude of risk reduction when a patient with CHD
      stops smoking. SEARCH STRATEGY: We searched the Cochrane Register of Controlled
      Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index, CINAHL, PsychLit,
      Dissertation Abstracts, BIDS ISI Index to Scientific and Technical Proceedings,
      UK National Research Register from the start of each database. Sixty-one large
      international cohort studies of cardiovascular disease were identified, and
      contact made with authors to search for any unpublished results. The search was
      supplemented by cross-checking references and contact with various experts. Date
      of last search was April 2003. SELECTION CRITERIA: Any prospective cohort studies
      of patients with a diagnosis of CHD, which include all-cause mortality as an
      outcome measure. Smoking status must be measured on at least two occasions to
      ascertain which smokers have quit, and followed-up for at least two years. DATA
      COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed
      independently by two reviewers. MAIN RESULTS: Twenty studies were included. There
      was a 36% reduction in crude relative risk (RR) of mortality for those who quit
      smoking compared with those who continued to smoke (RR 0.64, 95% confidence
      interval 0.58 to 0.71). There was also a reduction in non-fatal myocardial
      infarctions (crude RR 0.68, 95% confidence interval 0.57 to 0.82). Many studies
      did not adequately address quality issues, such as control of confounding, and
      misclassification of smoking status. However, there was little difference in the
      results for the six 'higher quality' studies, and little heterogeneity between
      these studies. This review was not able to assess how quickly the risk of
      mortality was reduced. REVIEWER'S CONCLUSIONS: Quitting smoking is associated
      with a substantial reduction in risk of all-cause mortality among patients with
      CHD. The pooled crude RR was 0.64 (95% CI 0.58 to 0.71). This 36% risk reduction
      appears substantial compared with other secondary preventive therapies such as
      cholesterol lowering which have received greater attention in recent years. The
      risk reduction associated with quitting smoking seems consistent regardless of
      differences between the studies in terms of index cardiac events, age, sex,
      country, and time period. However, relatively few studies have included large
      numbers of older people, women, or people of non-European descent, and most were
      carried out in Western countries.

PMID- 14974004
TI  - Hyperbaric oxygen therapy for multiple sclerosis.
AB  - BACKGROUND: Multiple Sclerosis (MS) is a chronic, recurrent and progressive
      illness with no cure. On the basis of speculative pathophysiology, it has been
      suggested that Hyperbaric Oxygen Therapy (HBOT) may slow or reverse the progress
      of the disease. OBJECTIVES: The object of this review was to evaluate the
      efficacy and safety of HBOT in the treatment of MS. SEARCH STRATEGY: We searched
      the Cochrane MS Group trials register (July 2002), the Cochrane Central Register
      of Controlled Trials (The Cochrane Library, Issue 2, 2002), MEDLINE (January 1966
      to October 2002) and the National Library of Medicine (NLM) database (July 2002),
      along with specialised hyperbaric resources and handsearching of relevant
      journals and proceedings. SELECTION CRITERIA: All randomised, controlled trials
      involving a comparison between HBOT and a sham therapy in MS were evaluated. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently appraised all comparative
      trials identified, extracted data and scored them for methodological quality.
      MAIN RESULTS: We identified ten reports of nine trials that satisfied selection
      criteria (504 participants in total). Two trials produced generally positive
      results, while the remaining seven reported generally no evidence of a treatment
      effect. None of our three a priori subgroup analyses placed these two trials in
      the same group and were therefore unable to account for this difference. Three
      analyses (of 21) did indicate some benefit. For example, the mean Expanded
      Disability Status Scale (EDSS) at 12 months was improved in the HBOT group (group
      mean reduction in EDSS compared to sham -0.85 of a point, 95% confidence interval
      -1.28 to -0.42, P = 0.0001). Only the two generally positive trials reported on
      this outcome at this time (16% of the total participants in this review).
      REVIEWER'S CONCLUSIONS: We found no consistent evidence to confirm a beneficial
      effect of hyperbaric oxygen therapy for the treatment of multiple sclerosis and
      do not believe routine use is justified. The small number of analyses suggestive
      of benefit are isolated, difficult to ascribe with biological plausibility and
      would need to be confirmed in future well-designed trials. Such trials are not,
      in our view, justified by this review.

PMID- 14974005
TI  - Occupational therapy for rheumatoid arthritis.
AB  - BACKGROUND: For persons with rheumatoid arthritis (RA) the physical, personal,
      familial, social and vocational consequences are extensive. Occupational therapy
      (OT), with the aim to facilitate task performance and to decrease the
      consequences of rheumatoid arthritis for daily life activities, is considered to
      be a cornerstone in the management of rheumatoid arthritis. Till now the efficacy
      of occupational therapy for patients with rheumatoid arthritis on functional
      performance and social participation has not been systematically reviewed.
      OBJECTIVES: To determine whether OT interventions (classified as comprehensive
      therapy, training of motor function, training of skills, instruction on joint
      protection and energy conservation, counseling, instruction about assistive
      devices and provision of splints) for rheumatoid arthritis patients improve
      outcome on functional ability, social participation and/or health related quality
      of life. SEARCH STRATEGY: Relevant full length articles were identified by
      electronic searches in Medline, Cinahl, Embase, Amed, Scisearch and the Cochrane
      Musculoskeletal group Specialised Register. The reference list of identified
      studies and reviews were examined for additional references. Date of last search:
      December 2002. SELECTION CRITERIA: Controlled (randomized and non-randomized) and
      other than controlled studies (OD) addressing OT for RA patients were eligible
      for inclusion. DATA COLLECTION AND ANALYSIS: The methodological quality of the
      included trials was independently assessed by two reviewers. Disagreements were
      resolved by discussion. A list proposed by Van Tulder et al. (Van Tulder 1997)
      was used to assess the methodological quality. For outcome measures, standardized
      mean differences were calculated. The results were analysed using a best evidence
      synthesis based on type of design, methodological quality and the significant
      findings of outcome and/or process measures. MAIN RESULTS: Thirty-eight out of 58
      identified occupational therapy studies fulfilled all inclusion criteria. Six
      controlled studies had a high methodological quality. Given the methodological
      constraints of uncontrolled studies, nine of these studies were judged to be of
      sufficient methodological quality. The results of the best evidence synthesis
      shows that there is strong evidence for the efficacy of "instruction on joint
      protection" (an absolute benefit of 17.5 to 22.5, relative benefit of 100%) and
      that limited evidence exists for comprehensive occupational therapy in improving
      functional ability (an absolute benefit of 8.7, relative benefit of 20%).
      Indicative findings for evidence that "provision of splints" decreases pain are
      found (absolute benefit of 1.0, relative benefit of 19%). REVIEWER'S CONCLUSIONS:
      There is evidence that occupational therapy has a positive effect on functional
      ability in patients with rheumatoid arthritis.

PMID- 14974006
TI  - Epinephrine for bronchiolitis.
AB  - BACKGROUND: Bronchodilators are commonly used in the management of bronchiolitis.
      A recent systematic review showed that bronchodilators produce modest short-term
      benefit among patients with mild or moderate bronchiolitis. OBJECTIVES: To
      compare epinephrine versus placebo and other bronchodilators in infants less than
      2 years of age with bronchiolitis. SEARCH STRATEGY: Electronic searches were
      conducted on the following bibliographic databases: The Cochrane Central Register
      of Controlled Trials (CENTRAL) (issue 1, 2003), MEDLINE (January 1966 to May
      2003), and EMBASE (January 1988 to May 2003). The reference lists of all selected
      articles were examined for relevant studies. Primary authors were contacted for
      information on additional trials. SELECTION CRITERIA: Studies were included if
      they: 1) were RCTs comparing epinephrine with placebo or other bronchodilator; 2)
      involved children less than two years with bronchiolitis; 3) presented at least
      one quantitative outcome. DATA COLLECTION AND ANALYSIS: Searches were screened
      and inclusion criteria applied independently by two reviewers. Quality was
      assessed by two reviewers using the Jadad scale and allocation concealment. Data
      were extracted by one reviewer using a structured form and checked by a second.
      Separate analyses were conducted for the two types of control groups (placebo,
      non-epinephrine bronchodilators) and for patient status (inpatient, outpatient).
      MAIN RESULTS: Fourteen studies were included. Quality ranged from one to five
      (Jadad scale) with a median of three (inter-quartile range: two to three).
      Allocation concealment was adequate in six trials and unclear in eight. Among
      inpatient studies comparing epinephrine and placebo (n = five), there was one
      significant outcome favouring epinephrine: change in clinical score at 60 minutes
      post-treatment (SMD -0.52; 95% CI -1.00,-0.03). For outpatient studies (n =
      three), change in clinical score at 60 minutes (SMD -0.81; -1.56,-0.07), change
      in oxygen saturation at 30 minutes (WMD 2.79;1.50,4.08), respiratory rate at 30
      minutes (WMD -4.54;-8.89-0.19), and "improvement" (OR 25.06; 4.95,126.91)
      favoured epinephrine. Heart rate at 60 minutes post-treatment favoured placebo
      (WMD 11.80; 5.20,18.40). Admission rates and change in oxygen saturation at 60
      minutes post-treatment were not significantly different. For inpatient studies
      comparing epinephrine and salbutamol (n = four), only one of the seven outcomes
      was statistically significant: respiratory rate at 30 minutes favoured
      epinephrine (WMD -5.12; -6.83;-3.41). Among outpatient studies (n = four), change
      in oxygen saturation at 60 minutes (WMD 1.91; 0.38,3.44), heart rate at 90
      minutes (WMD -14.00; -22.95;-5.05), respiratory rate at 60 minutes (WMD -7.76; 
      11.35,-4.17) post-treatment and "improvement" (OR 4.51; 1.93,10.53) favoured
      epinephrine. Admission rates were not significantly different (OR 0.40;
      0.12,1.33). Pallor at 30 minutes post-treatment was significantly higher in the
      epinephrine group (OR 6.00; 1.33,27.00). REVIEWER'S CONCLUSIONS: There is
      insufficient evidence to support the use of epinephrine for the treatment of
      bronchiolitis among inpatients. There is some evidence to suggest that
      epinephrine may be favourable to salbutamol and placebo among outpatients. A
      number of large, multi-centered trials are required to examine the effectiveness
      of epinephrine compared to placebo and salbutamol for infants presenting to
      outpatient settings. There is a need to develop a validated, reliable scoring
      system that is sensitive to important clinical changes in patients with
      bronchiolitis.

PMID- 14974007
TI  - Positive expiratory pressure physiotherapy for airway clearance in people with
      cystic fibrosis.
AB  - BACKGROUND: Chest physiotherapy is widely prescribed to assist the clearance of
      airway secretions in people with cystic fibrosis (CF). Positive expiratory
      pressure (PEP) devices provide constant back pressure to the airways during
      expiration. This may improve clearance by building up gas behind mucus via
      collateral ventilation. Given the widespread use of PEP devices, there is a need
      to determine the evidence for their effect. OBJECTIVES: To determine the
      effectiveness and acceptability of PEP devices compared to other forms of
      physiotherapy as a means of improving mucus clearance and other outcomes in
      people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and
      Genetic Disorders Group trials register comprising of references identified from
      comprehensive electronic database searches and handsearching of relevant journals
      and abstract books of conference proceedings. The electronic database CINAHL was
      also searched from 1982 to 2001. Most recent search of the Group's register:
      November 2003. SELECTION CRITERIA: Randomised controlled trials in which PEP was
      compared with any other form of physiotherapy in people with CF. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently applied the inclusion and exclusion
      criteria to publications and assessed the quality of the included studies. MAIN
      RESULTS: Thirty-three studies were identified and twenty studies involving 429
      participants met review inclusion criteria. Most included studies had low scores
      on a scale of study quality. Sixteen of these studies involving 257 participants
      were cross-over in design. Data were not published in sufficient detail in these
      studies to perform meta-analysis.Forced expiratory volume in one second (FEV1)
      was the most frequently measured outcome. Single interventions or series of
      treatments continued for up to one month demonstrated no significant difference
      in effect between PEP and other methods of airway clearance on FEV1. Long-term
      studies had equivocal or conflicting results regarding the effect on FEV1.
      Patient preference was reported in nine studies. In all studies with an
      intervention period of at least one month, measures of patient preference were in
      favour of PEP. The results for the remaining outcome measures were not examined
      or reported in sufficient detail to provide any high level evidence. REVIEWER'S
      CONCLUSIONS: There was no clear evidence that PEP was a more or less effective
      intervention overall than other forms of physiotherapy. There was limited
      evidence that PEP was preferred by participants compared to other techniques but
      this finding is from studies of low quality.

PMID- 14974008
TI  - Continuous infusion versus bolus injection of loop diuretics in congestive heart
      failure.
AB  - BACKGROUND: Loop diuretics, when given as intermittent bolus injections in
      acutely decompensated heart failure, may cause fluctuations in intravascular
      volume, increased toxicity and development of tolerance. Continuous infusion has
      been proposed to avoid these complications and result in greater diuresis,
      hopefully leading to faster symptom resolution, decrease in morbidity and
      possibly, mortality. OBJECTIVES: To compare the effects and adverse effects of
      continuous intravenous infusion of loop diuretics with those of bolus intravenous
      administration among patients with congestive heart failure Class III-IV. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The
      Cochrane Library Issue 2, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003)
      and the HERDIN database. We also contacted pharmaceutical companies. SELECTION
      CRITERIA: Randomized controlled trials comparing the efficacy of continuous
      intravenous infusion versus bolus intravenous administration of loop diuretics in
      congestive heart failure were included DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed study eligibility, methodological quality and
      did data extraction. Included studies were assessed for validity. Authors were
      contacted when feasible. Adverse effects information was collected from the
      trials. MAIN RESULTS: Eight trials involving 254 patients were included. In seven
      studies which reported on urine output, the output (as measured in cc/24 hours)
      was noted to be greater in patients given continuous infusion with a weighted
      mean difference (WMD) of 271 cc/24 hour (95%CI 93.1 to 449; p<0.01). Electrolyte
      disturbances (hypokalemia, hypomagnesemia) were not significantly different in
      the two treatment groups with a relative risk (RR) of 1.47 (95%CI 0.52 to 4.15;
      p=0.5). Less adverse effects (tinnitus and hearing loss) were noted when
      continuous infusion was given, RR 0.06 (95%CI 0.01 to 0.44; p=0.005). Based on a
      single study, the duration of hospital stay was significantly shortened by
      3.1days with continuous infusion WMD -3.1 (95%CI -4.06 to -2.20; p<0.0001) while
      cardiac mortality was not significantly different in the two treatment groups, RR
      0.47 (95% CI 0.33 to 0.69; p<0.0001). Based on two studies, all cause mortality
      was not significantly different in the two treatment groups, RR 0.52 (95%CI 0.38
      to 0.71; p<0.0001). REVIEWER'S CONCLUSIONS: Currently available data are
      insufficient to confidently assess the merits of the two methods of giving
      intravenous diuretics. Based on small and relatively heterogenous studies, this
      review showed greater diuresis and a better safety profile when loop diuretics
      were given as continuous infusion. The existing data still does not allow
      definitive recommendations for clinical practice and larger studies should be
      done to more adequately settle this issue.

PMID- 14974009
TI  - Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of
      malignant lymphoma.
AB  - BACKGROUND: Granulopoiesis-stimulating factors (G-CSF and GM-CSF) are being used
      to prevent febrile neutropenia and infections in the treatment of patients with
      malignant lymphoma. The question whether G-CSF and GM-CSF improve dose-intensity,
      tumour response and overall survival in this patient population has not been
      answered yet. Since the results from single studies are inconclusive a systematic
      review was required. OBJECTIVES: To undertake a systematic review in patients
      with malignant lymphoma to determine the effectiveness of G-CSF and GM-CSF to
      prevent neutropenia, febrile neutropenia, infection, improve quality of life,
      adherence to the treatment protocol, tumour response, freedom from treatment
      failure (FFTF), overall survival (OS) and to assess adverse events of G-CSF and
      GM-CSF. SEARCH STRATEGY: Medline, Embase, CancerLit, the Cochrane Library and
      smaller databases, Internet-databases of ongoing trials, conference proceedings
      of the American Society of Clinical Oncology and the American Society of
      Hematology were searched. We included full-text and abstract publications as well
      as unpublished data. SELECTION CRITERIA: Randomised controlled trials comparing
      prophylaxis with G-CSF or GM-CSF versus placebo/no prophylaxis in adult patients
      with malignant lymphoma undergoing chemotherapy were included in this review.
      Both study arms had to receive identical chemotherapy and supportive care. DATA
      COLLECTION AND ANALYSIS: Eligibility and quality assessment, data extraction and
      analysis were done in duplicate. Authors were contacted to obtain missing data.
      MAIN RESULTS: We included 12 eligible studies with 1.823 randomised patients.
      Compared with no prophylaxis, G-/GM-CSF significantly reduced the relative risk
      for severe neutropenia (RR 0.67 [95% CI 0.60-0.73]), febrile neutropenia (RR 0.74
      [95% CI 0.62-0.89]) and infection (RR 0.74 [95% CI 0.64-0.85]). There was no
      evidence for G-/GM-CSF to decrease the number of patients who required iv
      antibiotics (RR 0.82 [95%CI 0.57-1.18]), to reduce infection related mortality
      (RR 1.37 [95% CI 0.66-2.82]), or to improve complete tumour response (RR 1.02
      [95% CI 0.94-1.11]), FFTF (HR 1.11 [95% CI 0.91-1.35]) and OS (HR 1.00 [95% CI
      0.86-1.16]). One study evaluated quality of life parameters and did not find
      differences between the groups. REVIEWER'S CONCLUSIONS: G-CSF and GM-CSF, when
      given prophylactically in patients with malignant lymphoma undergoing
      conventional chemotherapy, reduce the risk of neutropenia, febrile neutropenia
      and infection. However, based on the currently available randomised trials in
      this clinical setting, there is no evidence for G-/GM-CSF to provide a
      significant advantage in terms of complete tumour response, FFTF and OS.

PMID- 14974010
TI  - Interventions for rosacea.
AB  - BACKGROUND: Rosacea is a common skin condition affecting the face, characterised
      by flushing, redness, pimples, pustules and dilated blood vessels. The eyes are
      often also involved. The cause of rosacea is unclear. It is a chronic disease,
      which can be controlled in most cases with appropriate treatment. Numerous
      treatments are in use although it is unclear which are best, and which are most
      appropriate for the different types of rosacea. OBJECTIVES: To assess and
      summarise current evidence for the efficacy and safety of treatments for rosacea.
      SEARCH STRATEGY: We searched the Skin Group Specialised Trials Register (March
      2002), Cochrane Central Register of Controlled Trials (CENTRAL, March 2002),
      MEDLINE (from 1966 to March 2002), EMBASE (from 1980 to March 2002), Biosis (from
      1970 to March 2002) and the Science Citation Index (from 1988 to March 2002).
      Reference lists of trials and key review articles were also searched. Relevant
      manufacturers and experts were contacted. SELECTION CRITERIA: Randomised
      controlled trials in people with moderate to severe rosacea were included.
      Studies judged by the reviewers to have seriously flawed methodology were
      excluded. DATA COLLECTION AND ANALYSIS: Study selection, assessment of
      methodological quality, data extraction and analysis were carried out by two
      independent reviewers. MAIN RESULTS: The evidence provided by twenty-two included
      studies was generally weak because of poor methodology and reporting. One of our
      primary outcome measures, 'quality of life', was not assessed in any of the
      studies. Only two studies of ocular rosacea could be included. Pooled data from
      two trials involving 174 participants indicated that topical metronidazole is
      more effective than placebo (odds ratio 5.96, 95% confidence interval 2.95 to
      12.06). Data from a between-patient trial (114 patients) and a within-patient
      trial (33 patients) of azelaic cream versus placebo were not pooled, but both
      showed good evidence of efficacy. Data pooled from three studies of oral
      tetracycline versus placebo involving 152 participants showed that, according to
      physicians' ratings, tetracycline was effective (odds ratio 6.06, 95% confidence
      interval 2.96 to 12.42). Some evidence of efficacy of oral metronidazole was
      provided by one small study. REVIEWER'S CONCLUSIONS: The quality of studies
      evaluating rosacea treatments was generally poor. There is evidence that topical
      metronidazole and azelaic acid cream have a therapeutic effect. There is some
      evidence that oral metronidazole and tetracycline are effective. There is
      insufficient evidence concerning the effectiveness of other treatments. As many
      of these treatments are used for rosacea, good RCTs are urgently needed.

PMID- 14974011
TI  - Azathioprine as an oral corticosteroid sparing agent for asthma.
AB  - BACKGROUND: For the majority of chronic asthmatics, symptoms are best controlled
      by using inhaled steroids. However, for a small group of asthmatics, symptoms can
      only be controlled by high doses of oral steroids. Continuous use of oral steroid
      is associated with severe side-effects, but it has been suggested that
      azathioprine, an immunosuppressive anti-metabolite, often used to reduce the
      immune response in chronic active hepatitis and severe rheumatoid arthritis,
      could be useful as an oral steroid sparing agent. There is a need to
      systematically evaluate the evidence regarding its use to reduce or eliminate
      oral corticosteroid usage. OBJECTIVES: The objective of this review is to assess
      the efficacy of adding azathioprine in patients with stable asthma who are
      dependent on oral corticosteroids with the intention of eventually minimizing or
      eliminating the use of these steroids. SEARCH STRATEGY: Searches of the Cochrane
      Airways Group asthma and wheeze trials register were undertaken with predefined
      search terms. Searches were current as of February 2003 SELECTION CRITERIA: Only
      studies with a randomised placebo-controlled design met the inclusion criteria
      for the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      assessed studies for suitability for inclusion in the review. Data were extracted
      and entered into RevMan 4.2.2. MAIN RESULTS: Two small trials recruiting 23
      participants met the inclusion criteria for the review. Participants may have
      been suffering from comorbid lung disease. No data on oral steroid consumption
      were reported. No significant differences were observed in the studies for
      FEV(1), FVC, PaO(2) and symptoms. One study reported a statistically significant
      difference in SGaw, but the clinical importance of this is uncertain. Due to
      concerns over the small sample sizes and methodological shortcomings in terms of
      inadequate washout in one study, and methods used in outcome assessment for both
      studies, the findings of the studies are not generalisable to the issue of
      steroid tapering. REVIEWER'S CONCLUSIONS: Currently there is a clear lack of
      evidence to support the use of azathioprine in the treatment of chronic asthma as
      a steroid sparing-agent. Large, long-term studies with pre-defined steroid
      reducing protocols are required before recommendations for clinical practice can
      be made.

PMID- 14974012
TI  - Physical fitness training for stroke patients.
AB  - BACKGROUND: Stroke patients have impaired physical fitness and this may
      exacerbate their disability. It is not known whether improving physical fitness
      after stroke reduces disability. OBJECTIVES: The primary aims of the review were
      to establish whether physical fitness training reduces death, dependence and
      disability after stroke. The secondary aims of the review included an
      investigation of the effects of fitness training on secondary outcome measures
      (including, physical fitness, mobility, physical function, health and quality of
      life, mood and the incidence of adverse events). SEARCH STRATEGY: We searched the
      Cochrane Stroke Group Trials Register (June 2003). In addition, the following
      electronic databases were searched: Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library, 2002 Issue 4), MEDLINE (1966 to December
      2002), EMBASE (1980 to December 2002), CINAHL (1982 to December 2002),
      SPORTDiscus (1949 to December 2002), Science Citation Index Expanded (1981 to
      December 2002), Web of Science Proceedings (1982 to December 2002), Physiotherapy
      Evidence Database (December 2002), REHABDATA (1956 to December 2002) and Index to
      UK Theses (1970 to December 2002). We hand searched relevant journals and
      conference proceedings and screened reference lists. To identify unpublished and
      ongoing trials we searched trials directories and contacted experts in the field.
      SELECTION CRITERIA: Randomised controlled trials were included when an
      intervention represented a clear attempt to improve either muscle strength and/or
      cardiorespiratory fitness, and whose control groups comprised either usual care
      or a non-exercise intervention. DATA COLLECTION AND ANALYSIS: Data from eligible
      studies were independently extracted by two reviewers. The primary outcome
      measures were death, disability and dependence. The lack of common outcome
      measures prevented some of the intended analysis. MAIN RESULTS: A total of twelve
      trials were included in the review. No trials reported death and dependence data.
      Two small trials reporting disability showed no evidence of benefit. The
      remaining available secondary outcome data suggest that cardiorespiratory
      training improves walking ability (mobility). Observed benefits appear to be
      associated with specific or 'task-related' training. REVIEWER'S CONCLUSIONS:
      There are few data available to guide clinical practice at present with regard to
      fitness training interventions after stroke. More general research is needed to
      explore the efficacy and feasibility of training, particularly soon after stroke.
      In addition more specific studies are required to explore the effect of content
      and type of training. Further research will require careful planning to address a
      number of issues peculiar to this type of intervention.

PMID- 14974013
TI  - Conservative treatments for whiplash.
AB  - BACKGROUND: Our previous review examining conservative treatments for whiplash
      was published in 2001. Since then, new trials have been published.Whiplash
      associated disorders (WAD) can be classified by the severity of signs and
      symptoms: WAD Grade 0 indicates no complaints or physical signs; Grade 1
      indicates neck complaints but no physical signs; Grade 2 indicates neck
      complaints and musculoskeletal signs; Grades 3 and 4 indicate neck complaints and
      neurological signs or fracture/dislocation, respectively. OBJECTIVES: To assess
      the effectiveness of conservative treatment in patients with WAD Grades 1 or 2.
      SEARCH STRATEGY: We completed a computerised search of CENTRAL, MEDLINE, EMBASE,
      CINAHL, PsycLIT, and PEDro, to April 2003. We also screened references of
      identified trials and relevant systematic reviews. SELECTION CRITERIA: Studies
      were selected if they were a (randomised) clinical trial, examined patients with
      a WAD, examined conservative treatments, measured one of: pain, global perceived
      effect or participation in daily activities, and were published in English,
      French, German or Dutch. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed the methodological quality using the Delphi list and
      extracted the data using standardised forms. Because the population,
      interventions and outcome measures were heterogeneous, we used a rating system
      with levels of evidence rather than statistical pooling for the analysis.
      Clinically relevant improvement was defined as a 15% improvement relative to a
      control. A pre-planned stratified analysis was performed in three groups. MAIN
      RESULTS: We found four new studies since the previous review, resulting in 15
      studies that met the inclusion criteria. Just one study evaluated patients with
      chronic WAD. Only three studies satisfied one of our criteria of high quality,
      indicating overall a poor methodological quality. The broad array of conservative
      interventions were divided into passive and active interventions and were
      compared with each other, no treatment, or a placebo group. There was limited
      evidence that both passive and active interventions seemed to be more effective
      than no treatment. Contrary to our earlier review, we found conflicting evidence
      about the effectiveness of active interventions compared to passive ones. All but
      one study mentioned positive results, but the actual data of the high quality
      studies were conflicting. REVIEWER'S CONCLUSIONS: When looking at the actual data
      presented in the current included trials, our conclusion from the previous
      version of this review, that 'rest makes rusty', can no longer be justified.
      There is a trend suggesting that active interventions are more effective than
      passive ones, but no clear conclusion can be drawn. We can draw no conclusion
      about the most effective therapy for patients with chronic WAD, because only one
      low quality trial was found.

PMID- 14974014
TI  - Psychological and/or educational interventions for the prevention of depression
      in children and adolescents.
AB  - BACKGROUND: Depression is the fourth most important disease in the estimation of
      the burden of disease Murray 1996 and is a common problem with prevalence rates
      estimated to be as high as 8% in young people. Depression in young people is
      associated with poor academic performance, social dysfunction, substance abuse,
      suicide attempts, and completed suicide (NHMRC 1997). This has precipitated the
      development of programmes aimed at preventing the onset of depression. This
      review evaluates evidence for the effectiveness of these prevention programmes.
      OBJECTIVES: To determine whether psychological and/or educational interventions
      (both universal and targeted) are effective in reducing risk of depressive
      disorder by reducing depressive symptoms immediately after intervention or by
      preventing the onset of depressive disorder in children and adolescents over the
      next one to three years. SEARCH STRATEGY: The Cochrane Depression, Anxiety and
      Neurosis Group trials register (August 2002), MEDLINE (1966 to December Week 3
      2002), EMBASE (1980 to January Week 2 2003), PsychInfo (1886 to January Week 2
      2003) and ERIC (1985 to December 2002) were searched. In addition, conference
      abstracts, the reference lists of included studies, and other reviews were
      searched and experts in the field were contacted. SELECTION CRITERIA: Each
      identified study was assessed for possible inclusion by two independent reviewers
      based on the methods sections. The determinants for inclusion were that the trial
      include a psychological and/or educational prevention programme for young people
      aged 5 to 19 years-old, who did not meet DSM or ICD criteria for depression
      and/or did not fall into the clinical range on standardised, validated, and
      reliable rating scales of depression. DATA COLLECTION AND ANALYSIS: The
      methodological quality of the included trials was assessed by two independent
      reviewers according to a list of pre-determined criteria, which were based on
      quality ratings devised by Moncrieff and colleagues (Moncrieff 2001). Outcome
      data was extracted and entered into Revman 4.2. Means and standard deviations for
      continuous outcomes and number of events for dichotomous outcomes were extracted
      where available. For trials where the required data were not reported or could
      not be calculated, further details were requested from first authors. If no
      further details were provided, the trial was included in the review and
      described, but not included in the meta-analysis. Results were presented for each
      type of intervention: targeted or universal interventions; and educational or
      psychological interventions and if data were provided, by gender. Where possible
      data were combined in meta-analyses to give a treatment effect across all trials.
      Sensitivity analysis were conducted on studies rated as "adequate" or "high"
      quality, that is with a score over 22, based on the scale by Moncrieff et al
      (Moncrieff 2001). The presence of publication bias was assessed using funnel
      plots. MAIN RESULTS: Studies were divided into those that compared intervention
      with an active comparison or placebo (i.e. a control condition that resembles the
      intervention being investigated but which lacks the elements thought to be active
      in preventing depression) and those that used a "wait-list" or no intervention
      comparison group. Only two studies fell into the former category and neither
      showed effectiveness although one study was inadequately powered to show a
      difference and in the other the "placebo" contained active therapeutic elements,
      reducing the ability to demonstrate a difference from intervention. Psychological
      interventions were effective compared with non-intervention immediately after the
      programmes were delivered with a significant reduction in scores on depression
      rating scales for targeted (standardised mean difference (SMD) of -0.26 and a 95%
      confidence interval (CI) of -0.40 to -0.13 ) but not universal interventions (SMD
      -0.21, 95% CI -0.48, 0.06), with a significant effect maintained on pooling data
      (SMD -0.26, 95% CI -0.36, -0.15). While small effect sizes were reported, these
      were associated with a significant reduction in depressive episodes. The overall
      risk difference after intervention translates to "numbers needed to treat" (NNT)
      of 10. The most effective study is the targeted programme by Clarke (Clarke 2001)
      where the initial effect size of -0.46 is associated with an initial risk
      difference of -0.22 and NNT 5. There was no evidence of effectiveness for
      educational interventions. Reports of effectiveness for boys and girls were
      contradictory. The quality of many studies was poor, and only two studies made
      allocation concealment explicit. Sensitivity analysis of only high quality
      studies did not alter the results significantly. The only analysis in which there
      was significant statistical heterogeneity was the sub-group analysis by gender
      where there was variability in the response to different programmes for both
      girls and boys. For the most part funnel plots indicate findings are robust for
      short term effects with no publication bias evident. There are too few studies to
      comment on whether there is publication bias for studies reporting long-term (12
      36 month) follow-up. REVIEWER'S CONCLUSIONS: Although there is insufficient
      evidence to warrant the introduction of depression prevention programmes
      currently, results to date indicate that further study would be worthwhile. There
      is a need to compare interventions with a placebo or some sort of active
      comparison so that study participants do not know whether they are in the
      intervention group or not, to investigate the impact of booster sessions to see
      if effectiveness immediately after intervention can be prolonged, ideally for a
      year or longer, and to consider practical implementation of prevention programmes
      when choosing target populations. Until now most studies have focussed on
      psychological interventions. The potential effectiveness of educational
      interventions has not been fully investigated. Given the gender differences in
      prevalence, and the change in these that occurs in adolescence with a
      disproportionate increase in prevalence rates for girls, it is likely that girls
      and boys will respond differently to interventions. Although differences have
      been reported in studies in this review the findings are contradictory and a more
      definitive delineation of gender specific responses to interventions would be
      helpful.

PMID- 14974015
TI  - Calcium channel blockers for preventing acute tubular necrosis in kidney
      transplant recipients.
AB  - BACKGROUND: The incidence of delayed graft function in cadaveric grafts has
      increased over the last few years due in part to the large demand for cadaveric
      kidneys necessitating the use of kidneys from marginal donors. Calcium channel
      blockers have the potential to reduce the incidence of post-transplant acute
      tubular necrosis (ATN) if given in the peri-operative period. However, there is
      controversy surrounding their use in this situation with no consensus as to their
      efficacy. OBJECTIVES: To evaluate the benefits and harms of using calcium channel
      blockers in the peri-transplant period in patients at risk of ATN following
      cadaveric kidney transplantation. SEARCH STRATEGY: We searched the Cochrane Renal
      Group's specialised register, the Cochrane Central Register of Controlled Trials
      (CENTRAL, in The Cochrane Library issue 2, 2003) MEDLINE (1966 to January 2003)
      and EMBASE (1980 - January 2003). The Trials Search Coordinator was contacted to
      develop the search strategy. SELECTION CRITERIA: Randomised controlled trials
      comparing calcium channel blockers given in the peri-transplant period with
      controls were included. Quasi-randomised trials were excluded. DATA COLLECTION
      AND ANALYSIS: Data was extracted and quality assessed independently by two
      reviewers, with differences resolved by discussion. Dichotomous outcomes are
      reported as relative risk (RR) and measurements on continuous scales are reported
      as weighted mean differences (WMD) with 95% confidence intervals (CI). MAIN
      RESULTS: Nine trials were suitable for inclusion. Treatment with calcium channel
      blockers in the peri-transplant period was associated with a significant decrease
      in the incidence of post transplant ATN (RR 0.57, 95%CI 0.40 to 0.82) and delayed
      graft function (RR 0.44, 95% CI 0.28 to 0.69). There was no difference between
      control and treatment groups in graft loss, mortality, requirement for
      haemodialysis. There was insufficient information to comment on adverse events.
      REVIEWER'S CONCLUSIONS: These results suggest that calcium channel blockers given
      in the peri-operative period may reduce the incidence of ATN post
      transplantation. The result should be treated with caution due to the
      heterogeneity of the trials which made comparison of studies and pooling of data
      difficult.

PMID- 14974016
TI  - Ergonomic and physiotherapeutic interventions for treating upper extremity work
      related disorders in adults.
AB  - BACKGROUND: Conservative interventions such as physiotherapy and ergonomic
      adjustments play a major part in the treatment of most work-related
      musculoskeletal disorders (WRMD). OBJECTIVES: The objective of this systematic
      review is to determine whether conservative interventions have a significant
      impact on short and long-term outcomes for upper extremity WRMD in adults. SEARCH
      STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised
      register (January 2002) and Cochrane Rehabilitation and Related Therapies Field
      specialised register (January 2002), the Cochrane Controlled Trials Register (The
      Cochrane Library Issue 3, 2001), PubMed (1966 to November 2001), EMBASE (1988 to
      November 2001), and CINAHL (1982 to November 2001). We also searched the
      Physiotherapy Index (1988 to November 2001) and reference lists of articles. No
      language restrictions were applied. SELECTION CRITERIA: Only randomised
      controlled trials and concurrent controlled trials studying conservative
      interventions for adults suffering from upper extremity WRMD were included.
      Conservative interventions may include exercises, relaxation, physical
      applications, biofeedback, myofeedback and work place adjustments. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently selected the trials from the
      search yield and assessed the clinical relevance and methodological quality using
      the Delphi list. In the event of clinical heterogeneity or lack of data we used a
      rating system to assess levels of evidence. MAIN RESULTS: We included 15 trials
      involving 925 people. Twelve trials included people with chronic non-specific
      neck or shoulder complaints, or non-specific upper extremity disorders. Over 20
      interventions were evaluated; seven main subgroups of interventions could be
      determined: exercises, manual therapy, massage, ergonomics, multidisciplinary
      treatment, energised splint and individual treatment versus group therapy.
      Overall, the quality of the studies appeared to be poor. In 10 studies a form of
      exercise was evaluated, and there is limited evidence about the effectiveness of
      exercises only when compared to no treatment. Concerning manual therapy (1
      study), massage (4 studies), multidisciplinary treatment (1 study) and energised
      splint (1 study) no conclusions can be drawn. Limited evidence is found
      concerning the effectiveness of specific keyboards for patients with carpal
      tunnel syndrome. REVIEWER'S CONCLUSIONS: This review shows limited evidence for
      the effectiveness of keyboards with an alternative force-displacement of the keys
      or an alternative geometry, and limited evidence for the effectiveness of
      individual exercises. The benefit of expensive ergonomic interventions (such as
      new chairs, new desks etc) in the workplace is not clearly demonstrated.

PMID- 14974017
TI  - Prophylactic oral antifungal agents to prevent systemic candida infection in
      preterm infants.
AB  - BACKGROUND: Systemic fungal infection has increased in prevalence in neonatal
      intensive care units (NICU) caring for very low birth weight infants. It is
      associated with a prolonged stay and an increase in morbidity and mortality. An
      assessment of the use of oral prophylactic antifungals to prevent systemic
      infection is needed. OBJECTIVES: To assess whether the prophylactic
      administration of oral antifungal agents to very preterm infants reduces the
      occurrence of systemic fungal infection. SEARCH STRATEGY: The standard methods of
      the Cochrane Collaboration and its Neonatal Review Group were used. Searches were
      carried out up to July 2003 on the Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library Issue 2, 2003), MEDLINE from 1966, EMBASE from
      1980, CINAHL from 1992. Abstracts from SPR (1993 - 2003) and ESPR (1995 to 2002)
      were hand searched. SELECTION CRITERIA: Randomized and quasi randomized
      controlled trials in very low birth weight or very preterm infants in which an
      oral antifungal agent was compared with placebo or no treatment or another oral
      antifungal agent DATA COLLECTION AND ANALYSIS: Data were extracted using the
      standard methods of the Cochrane Neonatal Review Group, with separate evaluation
      of the trial quality and data extraction undertaken by each author. Results were
      reported using relative risk (RR) and risk difference (RD) and weighted mean
      difference (WMD). 95% confidence intervals were reported. MAIN RESULTS: We
      identified three eligible trials, one comparing nystatin with no treatment (67
      infants), one comparing miconazole with placebo (600 infants), and one comparing
      nystatin with fluconazole (21 infants). As the two trials comparing nystatin or
      miconazole with placebo or no treatment were clinically quite different, meta
      analysis was not performed. In the trial of nystatin versus no treatment,
      systemic fungal infection was significantly reduced [RR 0.19 (0.04,0.78)] in the
      group treated with nystatin. In the study comparing miconazole with placebo there
      was no significant effect on systemic fungal infection [RR 1.32 (0.46,3.75)].
      Neither study found a significant effect on mortality, and there was no
      significant difference in the mean number of days infants received ventilation or
      stayed in the neonatal intensive care unit. In the small trial comparing oral
      fluconazole with nystatin, no significant difference in systemic fungal infection
      [RR 0.17 (0.01, 2.84)] or mortality [RR 0.17 (0.01, 2.84)] was reported. Adverse
      drug reactions were not reported in any study. REVIEWER'S CONCLUSIONS: There is
      insufficient evidence to support the use of prophylactic oral antifungal agents
      in very low birth weight infants in the neonatal intensive care unit. Randomised
      controlled trials in current neonatal practice settings are needed, comparing
      oral antifungal agents with placebo and with each other and including an
      assessment of side effects, in order to determine whether oral antifungal agents
      have a role in preventing systemic fungal infections in preterm infants.

PMID- 14974018
TI  - Prolonged versus short course of indomethacin for the treatment of patent ductus
      arteriosus in preterm infants.
AB  - BACKGROUND: Indomethacin is a prostaglandin inhibitor used to treat patent ductus
      arteriosus (PDA) in preterm infants. Although indomethacin produces ductal
      closure in the majority of cases, it is ineffective in up to 40% of patients.
      Furthermore, the ductus will re-open in up to 35% of infants who initially
      respond to the drug. A more prolonged course of indomethacin has been studied
      regarding the potential to achieve higher rates of ductal closure. OBJECTIVES: To
      determine if a prolonged course of indomethacin (compared to a short course)
      reduces the rate of treatment failure in preterm infants with PDA without
      unwanted side-effects. SEARCH STRATEGY: The search included review of personal
      files, abstracts of conferences, and the following electronic databases: MEDLINE
      (1966 to April 2003), EMBASE (1974 to April 2003), and Oxford Database of
      Perinatal Trials, Cochrane Central Register of Controlled Trials (The Cochrane
      Library, Issue 3, 2003). No language restrictions were applied. SELECTION
      CRITERIA: 1) DESIGN AND POPULATION: Randomized or quasi-randomized controlled
      trials including preterm infants with PDA diagnosed on clinical and/or
      echocardiographic examination.2) INTERVENTION: Indomethacin treatment by any
      route given as a long course (four or more doses) vs a short course (three or
      fewer doses). 3) OUTCOMES: Report of at least one of the following outcomes:
      failure of PDA to close, need for re-treatment, PDA re-opening, PDA ligation,
      mortality, duration of assisted ventilation, chronic lung disease (CLD), duration
      of supplemental oxygen dependence, intraventricular hemorrhage (IVH) (all and
      severe), diminished urine output, increased serum creatinine, necrotizing
      enterocolitis (NEC), bleeding diathesis, retinopathy of prematurity (ROP), and
      duration of hospital stay. DATA COLLECTION AND ANALYSIS: The three reviewers
      independently abstracted data from each study. Relative risk (RR) and Risk
      Difference (RD) with 95% confidence intervals (CI) using the fixed effect model
      for meta-analysis are reported. When a statistically significant RD was found,
      the number needed to treat (NNT) or number needed to harm (NNH) was also
      calculated with 95% CIs. A chi-square test was used to test for heterogeneity of
      results among included trials. MAIN RESULTS: Prolonged indomethacin treatment
      when compared to the short course resulted in a borderline statistically
      significant difference in PDA re-opening rate favoring the prolonged course [RR
      0.54 (95% CI 0.3, 0.99); RD -0.12 (95% CI -0.24, -0.01); NNT = 8 (4, 100). There
      was no statistically significant treatment effect on PDA closure, re-treatment,
      or ligation rates. The prolonged course was associated with a decreased incidence
      of severe IVH [RR 0.49 (95% CI 0.25, 0.98); RD -0.12 (95% CI -0.24, -0.01); NNT 8
      (4, 100)] and renal function impairment, as evidenced by a lower proportion of
      infants having an increased creatinine level [RR 0.52 (95% CI 0.34, 0.81); RD 
      0.20 (95% CI -0.33, -0.08); NNT 5 (3, 13)]. However, there was a trend for the
      prolonged course to increase the proportion of infants with CLD in the one trial
      reporting this outcome [RR 2.24 (95% CI 0.98, 5.12); RD 0.24 (95% CI 0.01,
      0.47)]. REVIEWER'S CONCLUSIONS:  IMPLICATIONS FOR PRACTICE: Prolonged as compared
      to short course of indomethacin for the treatment of PDA in preterm infants has a
      borderline effect on reducing the rate of PDA re-opening and it may be associated
      with an increased risk for CLD. However, prolonged course of indomethacin appears
      to reduce the risk of severe intracranial hemorrhage and renal impairment in this
      population. Definitive recommendations about the preferred duration of
      indomethacin therapy, i.e. prolonged versus short course, for the treatment of
      PDA in premature infants cannot be made based on the current findings of this
      review. IMPLICATIONS FOR RESEARCH: There is a paucity of data on optimal duration
      of indomethacin therapy for the treatment of PDA, in particular for ELBW
      premature infants. Future randomized clinical trials should include this high
      risk population and investigate the premature infants. Future randomized clinical
      trials should include this high risk population and investigate the possibility
      of tailoring duration of therapy (prolonged versus short) to individual response
      in terms of echocardiographic findings and/or prostaglandin levels, focusing on
      clinically significant outcomes and potential complications associated with
      either strategy. In addition, factors which may influence treatment effect need
      to be taken into account when designing such studies.

PMID- 14974019
TI  - Pre-operative education for hip or knee replacement.
AB  - BACKGROUND: Hip or knee replacement is a major surgical procedure which can be
      physically and psychologically stressful for patients. It is hypothesised that
      education before surgery reduces anxiety and enhances postoperative outcomes.
      OBJECTIVES: To determine whether preoperative education improves postoperative
      outcomes (anxiety, pain, mobility, length of stay and the incidence of deep vein
      thrombosis) in patients undergoing hip or knee replacement surgery. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The
      Cochrane Library issue 2, 2003), MEDLINE (1966 to April 2003), EMBASE (1980 to
      June 2002), CINAHL, PsycINFO and PEDro until May 2003. We handsearched the
      Australian Journal of Physiotherapy (1954 to 2001) and reviewed the reference
      lists. SELECTION CRITERIA: Randomised trials of preoperative education (verbal,
      written or audiovisual) delivered by a health professional within six weeks of
      surgery to patients undergoing hip or knee replacement. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently assessed study quality and extracted data.
      Continuous outcomes were combined using weighted mean difference (WMD) and 95%
      confidence intervals (CI). MAIN RESULTS: Nine studies involving 782 participants
      met the inclusion criteria. Four studies involving 365 participants assessed
      length of hospital stay (days) but detected no significant difference between
      preoperative education and usual care (WMD -0.97; 95% CI -2.67 to 0.73). However,
      one study of 133 participants with more complex needs, indicated that
      individually tailored programmes of education and support were beneficial in
      reducing length of stay. The four studies reporting length of stay did not find
      any significant effect of preoperative education on days to standing and days to
      climb stairs. Three trials found preoperative education was beneficial in
      reducing preoperative anxiety (WMD -5.64; -7.45 to -3.82) on a scale of 0 to 100.
      No significant effect on postoperative anxiety was detected either on the day
      following surgery, or at discharge. None of the five studies reporting
      postoperative pain detected any difference between the groups. REVIEWER'S
      CONCLUSIONS: There is little evidence to support the use of pre-operative
      education over and above standard care to improve postoperative outcomes in
      patients undergoing hip or knee replacement surgery, especially with respect to
      pain, functioning and length of hospital stay. There is evidence that
      preoperative education has a modest beneficial effect on preoperative anxiety.
      There may also be beneficial effects when preoperative education is tailored
      according to anxiety, or targeted at those most in need of support (e.g. those
      who are particularly disabled, or have limited social support structures).

PMID- 14974020
TI  - Trifluoperazine for schizophrenia.
AB  - BACKGROUND: Trifluoperazine is an inexpensive accessible 'high potency'
      antipsychotic drug, widely used to treat schizophrenia or related psychoses.
      OBJECTIVES: To estimate the effects of trifluoperazine compared with placebo and
      other drugs. SEARCH STRATEGY: Searches of the Cochrane Schizophrenia Group's
      register of trials (March 2002), supplemented with hand searching, reference
      searching, personal communication and contact with industry. SELECTION CRITERIA:
      All clinical randomised trials involving people with schizophrenia and comparing
      trifluoperazine with any other treatment. DATA COLLECTION AND ANALYSIS: Studies
      were reliably selected and quality rated and data was extracted. For dichotomous
      data, relative risks (RR) were estimated, with 95% confidence intervals (CI).
      Where possible, we undertook intention-to-treat analyses. For statistically
      significant results, the number needed to treat (NNT) was calculated. We
      estimated heterogeneity (I-square technique) and publication bias. MAIN RESULTS:
      1162 people from 13 studies were randomised to trifluoperazine or placebo. For
      global improvement, small short-term studies favoured trifluoperazine (n=95, 3
      RCTs, RR 0.62 CI 0.49 to 0.78 NNT 3 CI 2 to 4). Loss to follow up was about 12%
      in both groups (n=280, 7 RCTs, RR 0.99 CI 0.62 to 1.57) and more people allocated
      trifluoperazine used antiparkinson drugs to alleviate movements disorders
      compared with placebo (n=195, 4 RCTs, RR 5.06 CI 2.49 to 10.27, NNH 4 CI 2 to 9).
      2230 people from 49 studies were randomised to trifluoperazine or another older
      generation antipsychotic. Trifluoperazine was not clearly different in terms of
      'no substantial improvement' (n=1016, 27 RCTs, RR 1.06 CI 0.98 to 1.14) or
      leaving the study early (n=930, 22 RCTs, RR 1.15 CI 0.83 to 1.58). Almost
      identical numbers of people reported at least one adverse event (60%) in each
      group (n=585, 14 RCTs, RR 0.99 CI 0.87 to 1.13), although trifluoperazine was
      more likely to cause extrapyramidal adverse effects overall when compared to low
      potency antipsychotics such as chlorpromazine (n=130, 3 RCTs, RR 1.66 CI 1.03 to
      2.67, NNH 6 CI 3 to 121). One small study (n=38) found no clear differences
      between trifluoperazine and the atypical drug, sulpiride. REVIEWER'S CONCLUSIONS:
      Although there are shortcomings and gaps in the data, there appears to be enough
      consistency over different outcomes and periods to confirm that trifluoperazine
      is an antipsychotic of similar efficacy to other commonly used neuroleptics for
      people with schizophrenia. Its adverse events profile is similar to that of other
      drugs. It has been claimed that trifluoperazine is effective at low doses for
      patients with schizophrenia but this does not appear to be based on good quality
      trial based evidence.

PMID- 14974021
TI  - Dietary calcium supplementation for preventing colorectal cancer and adenomatous
      polyps.
AB  - BACKGROUND: Several dietary factors have been considered to be involved in the
      increasing incidence of colorectal cancer in industrialised countries.
      Experimental and epidemiological evidence has been suggestive but not conclusive
      for a protective role for high dietary calcium intake. Intervention studies with
      colorectal cancer as an endpoint are difficult to perform owing to the large
      number of patients and the long follow-up required; studies using the appearance
      of colorectal adenomatous polyps as a surrogate endpoint are therefore considered
      in reviewing the existing evidence. OBJECTIVES: This systematic review aims to
      assess the effect of supplementary dietary calcium on the incidence of colorectal
      cancer and the incidence or recurrence of adenomatous polyps. SEARCH STRATEGY: We
      searched the Cochrane Controlled Trials Register, the Cochrane Colorectal Cancer
      Group specialised register, MEDLINE, Cancerlit, and Embase, to April 2002. The
      reference lists of identified studies were inspected for further studies, and the
      review literature was scrutinized. SELECTION CRITERIA: Randomised controlled
      trials of the effects of dietary calcium on the development of colonic cancer and
      adenomatous polyps in humans are reviewed. Studies of healthy adults and studies
      of adults at higher risk of colon cancer due to family history, previous
      adenomatous polyps, or inflammatory bowel disease were considered; data from
      subjects with familial polyposis coli are excluded. The primary outcomes were the
      occurrence of colon cancer, and occurrence or recurrence of any new adenomas of
      the colon. Secondary outcomes were any adverse event that required
      discontinuation of calcium supplementation, and drop-outs before the end of the
      study. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data,
      assessed trial quality and resolved discrepancies by consensus. The outcomes were
      reported as odds ratios (OR) with 95% confidence intervals (CI). The data were
      combined with the fixed effects model. MAIN RESULTS: Two studies with 1346
      subjects met the inclusion criteria. Both trials were well designed, double -
      blind, placebo controlled trials, included participants with previous adenomas.
      The doses of supplementary elemental calcium used were 1200 mg daily for a mean
      duration of 4 years, and 2000 mg/day for three years. The rates of loss to follow
      -up were 14 % and 11%. For the development of recurrent colorectal adenoma, a
      reduction was found (OR 0.74, CI 0.58,0.95) when the results from both trials
      were combined. REVIEWER'S CONCLUSIONS: Although the evidence from two RCTs
      suggests that calcium supplementation might contribute to a moderate degree to
      the prevention of colorectal adenomatous polyps, this does not constitute
      sufficient evidence to recommend the general use of calcium supplements to
      prevent colorectal cancer.

PMID- 14974022
TI  - Tumor necrosis factor-alpha antibody for induction of remission in Crohn's
      disease.
AB  - BACKGROUND: Crohn's disease may be refractory to conventional treatments such as
      corticosteroids, enteral nutrition and immuno-suppressive agents. A number of
      patients with the disease may also become steroid-dependent leading to increased
      risk of developing steroid-related adverse effects. Recent studies suggest that
      TNF-a blocking agents may be effective in inducing remission in Crohn's disease.
      OBJECTIVES: To conduct a systematic review to evaluate the effectiveness of TNF-a
      blocking agents in inducing remission in patients with active Crohn's disease.
      SEARCH STRATEGY: We searched MEDLINE (1966-June 2003), EMBASE (1984-June 2003),
      the Cochrane Central Register of Controlled Trials from the Cochrane Library
      (Issue 2, 2003) and the IBD Review Group Specialized Trials Register. We hand
      searched the articles cited in each publication obtained. SELECTION CRITERIA: We
      included only randomised controlled trials in which patients with active Crohn's
      disease (defined by a validated Crohn's disease activity index) were randomly
      allocated to receive a TNF-a blocking agent in the treatment arm, or to receive
      placebo or another treatment in the comparison arm. DATA COLLECTION AND ANALYSIS:
      Data extraction and assessment of the methodological quality of each trial were
      independently performed by two reviewers. Any disagreement among reviewers was
      resolved by consensus. Outcome measures reported in the primary studies included
      clinical remission, clinical response and changes in disease activity index. MAIN
      RESULTS: Ten studies were identified of which 4 met the inclusion criteria. The
      included studies either differed in the type of TNF-a blocking agent used or in
      the way outcomes were assessed to such an extent that we considered it
      inappropriate to combine the data statistically. There is evidence from one
      randomised controlled trial that suggests that a single intravenous infusion of
      the monoclonal antibody cA2, infliximab, may be effective for induction of
      remission in Crohn's disease. There was no difference in response rates among
      infliximab doses of 5, 10 or 20 mg/kg. The results of two other trials suggested
      that CDP571, the genetically engineered human TNF monoclonal antibody, may also
      be effective in reducing disease activity index at 2 weeks after an infusion. We
      did not find any evidence to support the use of etanercept in Crohn's disease.
      REVIEWER'S CONCLUSIONS: Evidence from one randomized controlled trial suggests
      that a single infusion of infliximab may be effective for induction of remission
      in Crohn's disease. Based on this study, we can recommend a dose of 5 mg/kg.
      There is also some evidence that CDP571 may be effective in inducing remission in
      Crohn's disease. We did not find any evidence that supports the use of etanercept
      in Crohn's disease. The period of follow up for the patients in these studies was
      probably too short to allow adequate assessment of recently reported serious
      adverse effects such as tuberculosis and lymphoma.

PMID- 14974023
TI  - Interventions for treating collagenous colitis.
AB  - BACKGROUND: Collagenous colitis is a disorder that is recognized as a cause of
      chronic diarrhea. Treatment has been based mainly on anecdotal evidence. This
      review was performed to identify therapies for collagenous colitis that have been
      proven in randomized trials. OBJECTIVES: To determine effective treatments for
      patients with clinically active collagenous colitis. SEARCH STRATEGY: Relevant
      papers published between 1970 and August 2003 were identified via the MEDLINE and
      PUBMED databases. Manual searches from the references of identified papers, as
      well as review papers on collagenous or microscopic colitis were performed to
      identify additional studies. Abstracts from major gastroenterological meetings
      were searched to identify research submitted in abstract form only. Finally, the
      Cochrane Controlled Trials Register and the Cochrane Inflammatory Bowel Disease
      Group Specialized Trials Register were searched for other studies. SELECTION
      CRITERIA: Five randomized trials were identified. One trial studied bismuth
      subsalicylate (published in abstract form only), one trial studied prednisolone,
      and 3 trials studied budesonide in the therapy of collagenous colitis. DATA
      COLLECTION AND ANALYSIS: Data were extracted independently by each author onto
      2x2 tables (treatment versus placebo and response versus no response). For
      therapies assessed in one trial only, p-values were derived using the chi-square
      test. For therapies assessed in more than one trial, summary test statistics were
      derived using the Peto odds ratio and 95% confidence intervals. Data were
      combined for analysis only if the outcomes were sufficiently similar in
      definition. MAIN RESULTS: There were 9 patients with collagenous colitis in the
      trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks).
      Those randomized to active drug were more likely to have clinical (p=0.003) and
      histological (p=0.003) improvement than those assigned to placebo. Eleven
      patients were enrolled in the trial studying prednisolone (50 mg daily for 2
      weeks). There was a trend towards clinical response in patients on active
      medication compared to placebo (p=0.064). The effect of prednisolone on
      histologic improvement was not studied. A total of 94 patients were enrolled in 3
      trials studying budesonide (9 mg daily or in a tapering schedule for 6 to 8
      weeks). The pooled odds ratio for clinical response to treatment with budesonide
      was 12.32 (95% CI 5.53-27.46), with a number needed to treat of 2 patients. There
      was significant histological improvement with treatment in all 3 trials studying
      budesonide therapy. REVIEWER'S CONCLUSIONS: Budesonide is effective for the
      treatment of collagenous colitis. The evidence for benefit with bismuth
      subsalicylate is weaker. Prednisolone may be effective for treatment of
      collagenous colitis, but only a single very small study has been reported. The
      effectiveness of these and other therapies for induction or maintenance of
      remission (as opposed to producing clinical or histological improvement) of
      collagenous colitis is unknown.

PMID- 14974024
TI  - Bed rest in singleton pregnancies for preventing preterm birth.
AB  - BACKGROUND: Bed rest in hospital or at home is widely recommended for the
      prevention of preterm birth. This advice is based on the observation that hard
      work and hard physical activity during pregnancy could be associated with preterm
      birth and with the idea that bed rest could reduce uterine activity. However, bed
      rest may have some adverse effects on other outcomes. OBJECTIVES: To evaluate the
      effect of prescription of bed rest in hospital or at home for preventing preterm
      birth in pregnant women at high risk of preterm birth. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group trials register (July 2003),
      the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue
      2, 2003), MEDLINE (July 2003), LILACS (July 2003), EMBASE (July 2003), POPLINE
      (July 2003) and bibliographies of relevant papers. SELECTION CRITERIA: Randomized
      and quasi-randomized controlled trials with reported data that assess clinical
      outcomes in women at high risk of spontaneous preterm birth who were prescribed
      bed rest in hospital or at home for preventing preterm birth, and their babies.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility,
      trial quality and extracted data. MAIN RESULTS: One study met the inclusion
      criteria (1266 women). This trial has uncertain methodological quality due to
      lack of reporting. Four hundred and thirty-two women were prescribed bed rest at
      home and a total of 834 women received a placebo (412) or no intervention (422).
      Preterm birth before 37 weeks was similar in both groups (7.9% in the
      intervention group versus 8.5% in the control group), and the relative risk was
      0.92 with a 95% confidence interval from 0.62 to 1.37. No other results were
      available. REVIEWER'S CONCLUSIONS: There is no evidence, either supporting or
      refuting the use of bed rest at home or in hospital, to prevent preterm birth.
      Although bed rest in hospital or at home is widely used as the first step of
      treatment, there is no evidence that this practice could be beneficial. Due to
      the potential adverse effects that bed rest could have on women and their
      families, and the increased costs for the healthcare system, clinicians should
      not routinely advise women to rest in bed to prevent preterm birth. Potential
      benefits and harms should be discussed with women facing an increased risk of
      preterm birth. Appropriate research is mandatory. Future trials should evaluate
      both the effectiveness of bed rest, and the effectiveness of the prescription of
      bed rest, to prevent preterm birth.

PMID- 14974025
TI  - Artificial and bioartificial support systems for liver failure.
AB  - BACKGROUND: Artificial and bioartificial liver support systems may 'bridge'
      patients with acute or acute-on-chronic liver failure to liver transplantation or
      recovery. OBJECTIVES: To evaluate beneficial and harmful effects of artificial
      and bioartificial support systems for acute and acute-on-chronic liver failure.
      SEARCH STRATEGY: Trials were identified through The Cochrane Hepato-Biliary Group
      Controlled Trials Register (September 2002), The Cochrane Central Register of
      Controlled Trials on The Cochrane Library (Issue 3, 2002), MEDLINE (1966 -
      September 2002), EMBASE (1985 - September 2002), and The Chinese Biomedical
      Database (September 2002), manual searches of bibliographies and journals,
      authors of trials, and pharmaceutical companies. SELECTION CRITERIA: Randomised
      clinical trials on artificial or bioartificial support systems for acute or acute
      on-chronic liver failure were included irrespective of blinding, publication
      status, or language. Non-randomised studies were included in explorative
      analyses. DATA COLLECTION AND ANALYSIS: Data were extracted independently by
      three reviewers. Results were presented as relative risks (RR) with 95%
      confidence intervals (CI). Sources of heterogeneity were explored through
      sensitivity analyses and meta-regression. The primary outcome was mortality. MAIN
      RESULTS: Twelve trials on artificial or bioartificial support systems versus
      standard medical therapy (483 patients) and two trials comparing different
      artificial support systems (105 patients) were included. Most trials had unclear
      methodological quality. Compared to standard medical therapy, support systems had
      no significant effect on mortality (RR 0.86; 95% CI 0.65-1.12) or bridging to
      liver transplantation (RR 0.87; 95% CI 0.73-1.05), but a significant beneficial
      effect on hepatic encephalopathy (RR 0.67; 95% CI 0.52-0.86). Meta-regression
      indicated that the effect of support systems depended on the type of liver
      failure (P = 0.03). In subgroup analyses, artificial support systems appeared to
      reduce mortality by 33% in acute-on-chronic liver failure (RR 0.67; 95% CI 0.51
      0.90), but not in acute liver failure (RR 0.95; 95% CI 0.71-1.29). Two trials
      comparing artificial support systems showed significant mortality reductions with
      intermittent versus continuous haemofiltration (RR 0.58; 95% CI 0.36-0.94) and no
      significant difference between five versus ten hours of charcoal haemoperfusion
      (RR 1.03; 95% CI 0.65-1.62). The incidence of adverse events was inconsistently
      reported. REVIEWER'S CONCLUSIONS: This Review indicates that artificial support
      systems may reduce mortality in acute-on-chronic liver failure. Artificial and
      bioartificial support systems did not appear to affect mortality in acute liver
      failure. However, considering the strength of the evidence additional randomised
      clinical trials are needed before any support system can be recommended for
      routine use.

PMID- 14974026
TI  - Cerebrospinal fluid drainage for thoracic and thoracoabdominal aortic aneurysm
      surgery.
AB  - BACKGROUND: During aortic aneurysm surgery, cross-clamping can lead to inadequate
      blood supply to the spinal cord resulting in neurological deficit. Cerebrospinal
      fluid drainage (CSFD) may increase the perfusion pressure to the spinal cord and
      hence reduce the risk of ischaemic spinal cord injury. OBJECTIVES: To determine
      the effect of CSFD during thoracic and thoracoabdominal aortic aneurysm (TAAA)
      surgery on the risk of developing spinal cord injury. SEARCH STRATEGY: The
      reviewers searched the Cochrane Peripheral Vascular Diseases Group Specialised
      Trials Register (last searched October 2003), the Cochrane Central Register of
      Controlled Trials (CENTRAL) database (last searched Issue 4, 2003), MEDLINE and
      EMBASE, and reference lists of relevant articles. Recent conference proceedings
      were scanned. SELECTION CRITERIA: Randomised trials involving CSFD during
      thoracic and TAAA surgery. DATA COLLECTION AND ANALYSIS: Both reviewers assessed
      the quality of trials independently. One reviewer (SNK) extracted data and the
      other reviewer (GS) verified the data. MAIN RESULTS: Three trials, with a total
      of 287 participants operated on for type I or II TAAA, were included. In the
      first trial of 98 patients, neurological deficits in the lower extremities
      occurred in 14 (30%) CSFD and 17 (33%) controls. The deficit was observed within
      24 hours of the operation in 21 (68%), and from 3 to 22 days in 10 (32%). CSFD
      did not have a significant benefit in preventing ischaemic injury to the spinal
      cord. The second trial of 33 patients used a combination of CSFD and intrathecal
      papaverine. It showed a statistically significant reduction in the rate of
      postoperative neurological deficit (p = 0.039), compared to controls. Analysis
      was undertaken after only one third of the estimated sample size had entered the
      trial. In the third trial TAAA repair was performed on 145 patients. CSFD was
      initiated during the operation and continued for 48 hours after surgery.
      Paraplegia or paraparesis occurred in 9 of 74 patients (12.2%) in the control
      group versus 2 of 82 patients (2.7%) with CSFD (p = 0.03). Overall, CSFD resulted
      in an 80% reduction in the relative risk of postoperative deficits. Meta-analysis
      showed an odds ratio (OR) of 0.48 (0.25 to 0.92; confidence interval (CI) 95%).
      For CSFD trials only OR was 0.57 (0.28 to 1.17) and for intention-to-treat in
      CSFD only studies OR remained unchanged. REVIEWER'S CONCLUSIONS: There are
      limited data supporting the role of CSFD in thoracic and thoracoabdominal
      aneurysm surgery for prevention of neurological injury. Further clinical and
      experimental studies are indicated.

PMID- 14974027
TI  - Advice to reduce dietary salt for prevention of cardiovascular disease.
AB  - BACKGROUND: Restricting sodium intake in elevated blood pressure over short
      periods of time reduces blood pressure. Long term effects (on mortality,
      morbidity or blood pressure) of advice to reduce salt in patients with elevated
      or normal blood pressure are unclear. OBJECTIVES: To assess in adults the long
      term effects (mortality, cardiovascular events, blood pressure, quality of life,
      weight, urinary sodium excretion, other nutrients and use of anti-hypertensive
      medications) of advice to restrict dietary sodium using all relevant randomised
      controlled trials. SEARCH STRATEGY: The Cochrane Library, MEDLINE, EMBASE,
      bibliographies of included studies and related systematic reviews were searched
      for unconfounded randomised trials in healthy adults aiming to reduce sodium
      intake over at least 6 months. Attempts were made to trace unpublished or missed
      studies and authors of all included trials were contacted. There were no language
      restrictions. SELECTION CRITERIA: Inclusion decisions were independently
      duplicated and based on the following criteria: 1) randomisation was adequate; 2)
      there was a usual or control diet group; 3) the intervention aimed to reduce
      sodium intake; 4) the intervention was not multifactorial; 5) the participants
      were not children, acutely ill, pregnant or institutionalised; 6) follow-up was
      at least 26 weeks; 7) data on any of the outcomes of interest were available.
      DATA COLLECTION AND ANALYSIS: Decisions on validity and data extraction were made
      independently by two reviewers, disagreements were resolved by discussion or if
      necessary by a third reviewer. Random effects meta-analysis, sub-grouping,
      sensitivity analysis and meta-regression were performed. MAIN RESULTS: Three
      trials in normotensives (n=2326), five in untreated hypertensives (n=387) and
      three in treated hypertensives (n=801) were included, with follow up from six
      months to seven years. The large, high quality (and therefore most informative)
      studies used intensive behavioural interventions. Deaths and cardiovascular
      events were inconsistently defined and reported; only 17 deaths equally
      distributed between intervention and control groups occurred. Systolic and
      diastolic blood pressures were reduced at 13 to 60 months in those given low
      sodium advice as compared with controls (systolic by 1.1 mm Hg, 95% CI 1.8 to
      0.4, diastolic by 0.6 mm hg, 95% CI 1.5 to -0.3), as was urinary 24 hour sodium
      excretion (by 35.5 mmol/ 24 hours, 95% CI 47.2 to 23.9). Degree of reduction in
      sodium intake and change in blood pressure were not related. People on anti
      hypertensive medications were able to stop their medication more often on a
      reduced sodium diet as compared with controls, while maintaining similar blood
      pressure control. REVIEWER'S CONCLUSIONS: Intensive interventions, unsuited to
      primary care or population prevention programmes, provide only minimal reductions
      in blood pressure during long-term trials. Further evaluations to assess effects
      on morbidity and mortality outcomes are needed for populations as a whole and for
      patients with elevated blood pressure. Evidence from a large and small trial
      showed that a low sodium diet helps in maintenance of lower blood pressure
      following withdrawal of antihypertensives. If this is confirmed, with no increase
      in cardiovascular events, then targeting of comprehensive dietary and behavioural
      programmes in patients with elevated blood pressure requiring drug treatment
      would be justified.

PMID- 14974028
TI  - Auditory integration training and other sound therapies for autism spectrum
      disorders.
AB  - BACKGROUND: Autism spectrum disorders (ASD) are a heterogeneous group of
      disorders encompassing Autistic Disorder, Asperger's Disorder, Semantic-Pragmatic
      disorder and Pervasive Developmental Disorder Not Otherwise Specified. Auditory
      integration therapy (AIT) was developed as a technique for improving abnormal
      sound sensitivity in individuals with behavioural disorders including autism.
      Other sound therapies bearing similarities to AIT include the Tomatis Method and
      Samonas Sound Therapy. OBJECTIVES: To determine the effectiveness of AIT or other
      methods of sound therapy in individuals with ASD. SEARCH STRATEGY: We searched
      the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 2,
      2003), MEDLINE (1966 - February 2002), EMBASE (1980 - February 2002), CINAHL
      (1982 - December 2001), PsycINFO (1887 - February 2002), ERIC (1965 - December
      2001) and LILACS (1982 - March 2002). Reference lists of articles identified
      electronically were searched for further relevant publications. SELECTION
      CRITERIA: Randomised controlled trials of adults or children with ASD. Treatment
      was auditory integration therapy (AIT) or other sound therapies involving
      listening to music modified by filtering and modulation. Control groups could be
      no treatment, waiting list, usual therapy or placebo equivalent. Outcomes sought
      were changes in core and associated features of ASD, auditory processing, quality
      of life and adverse events. DATA COLLECTION AND ANALYSIS: All outcome data
      reported in included papers were continuous. Initial intention was to undertake
      meta-analyses using mean difference and standard deviation to take into account
      differences between treatment and control groups at baseline. These data were not
      available. Instead, point estimates and standard errors were calculated from t
      test scores and post intervention means. Meta-analysis was attempted but deemed
      inappropriate at present. MAIN RESULTS: No trials assessing sound therapies other
      than AIT were found. Six RCTs of AIT, including one cross-over trial, were
      identified with a total of 171 individuals aged 3-39 years. Four trials had fewer
      than 20 participants. Allocation concealment was inadequate for all of the
      studies. Seventeen different outcome measures were used. Only two outcomes were
      used by three or more studies: Aberrant Behaviour Checklist (ABC) (5) and
      Fisher's Auditory Problems Checklist (FAPC) (3). Meta-analysis was not possible
      due to very high heterogeneity (Aberrant Behaviour Checklist subscores), or
      presentation of data in unusable forms. Three studies (Bettison 1996, Zollweg
      1997, Mudford 2000) did not demonstrate benefit of AIT over control conditions.
      The remaining trials (Veale 1993, Rimland 1995, Edelson 1999) reported
      improvements at 3 months for the AIT group based on improvements of total mean
      scores for the ABC, which is of questionable validity. Rimland 1995 also reported
      improvements at 3 months in the AIT group for ABC subgroup scores. No significant
      adverse effects of AIT were reported. REVIEWER'S CONCLUSIONS: More research is
      needed to inform parents', carers' and practitioners' decision making about this
      therapy for individuals with autism spectrum disorders.

PMID- 14974029
TI  - Exercise to improve self-esteem in children and young people.
AB  - BACKGROUND: Psychological and behavioural problems in children and adolescents
      are common, and improving self-esteem may help to prevent the development of such
      problems. There is strong evidence for the positive physical health outcomes of
      exercise, but the evidence of exercise on mental health is scarce. OBJECTIVES: To
      determine if exercise alone or exercise as part of a comprehensive intervention
      can improve self-esteem among children and young people. SEARCH STRATEGY:
      Computerised searches in MEDLINE, EMBASE, The Cochrane Controlled Trials Register
      (CENTRAL), CINAHL, PsycINFO and ERIC were undertaken and reference lists from
      relevant articles were scanned. Relevant studies were also traced by contacting
      authors. Dates of most recent searches: May 2003 in (CENTRAL), all others:
      January 2002. SELECTION CRITERIA: Randomised controlled trials where the study
      population consisted of children and young people aged from 3 to 20 years, in
      which one intervention arm was gross motor activity for more than four weeks and
      the outcome measure was self-esteem. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently selected trials for inclusion, assessed the validity of included
      trials and extracted data. Investigators were contacted to collect missing data
      or for clarification when necessary. MAIN RESULTS: Twenty-three trials with a
      total of 1821 children and young people were included. Generally, the trials were
      small, and only one was assessed to have a low risk of bias. Thirteen trials
      compared exercise alone with no intervention. Eight were included in the meta
      analysis, and overall the results were heteregeneous. One study with a low risk
      of bias showed a standardised mean difference (SMD) of 1.33 (95% CI 0.43 to
      2.23), while the SMD's for the three studies with a moderate risk of bias and the
      four studies with a high risk of bias was 0.21 (95% CI -0.17 to 0.59) and 0.57
      (95% CI 0.11 to 1.04), respectively. Twelve trials compared exercise as part of a
      comprehensive programme with no intervention. Only four provided data sufficient
      to calculate overall effects, and the results indicate a moderate short-term
      difference in self-esteem in favour of the intervention [SMD 0.51 (95% CI 0.15 to
      0.88)]. REVIEWER'S CONCLUSIONS: The results indicate that exercise has positive
      short-term effects on self-esteem in children and young people. Since there are
      no known negative effects of exercise and many positive effects on physical
      health, exercise may be an important measure in improving children's self-esteem.
      These conclusions are based on several small low-quality trials.

PMID- 14974030
TI  - Thrombolysis for cerebral vein and dural sinus thrombosis.
AB  - BACKGROUND: Treatment of cerebral sinus thrombosis with thrombolytics has been
      reported in cases with a deteriorating clinical course despite anticoagulant
      therapy. The rationale of this treatment is to promote rapid recanalisation of
      the occluded sinus. OBJECTIVES: To review the available evidence on the efficacy
      and safety of thrombolysis in confirmed cerebral sinus thrombosis. SEARCH
      STRATEGY: We searched the Cochrane Stroke Group trials register (March 2003), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1,
      2003), MEDLINE (1966 to March 2003), EMBASE (1980 to March 2003), and reference
      lists of all relevant publications. SELECTION CRITERIA: We aimed to analyse
      separately unconfounded randomised controlled trials comparing thrombolytic agent
      with placebo, or thrombolytic agent with antithrombotic therapy, or thrombolytic
      agent and antithrombotic with antithrombotic alone, in patients with dural sinus
      thrombosis (confirmed by MR venography, intra-arterial venography or CT
      venography). DATA COLLECTION AND ANALYSIS: Two groups of reviewers independently
      applied the inclusion criteria. MAIN RESULTS: No randomised controlled trials
      were found. REVIEWER'S CONCLUSIONS: There is currently no available evidence from
      randomised controlled trials regarding the efficacy or safety of thrombolytic
      therapy in dural sinus thrombosis. A randomised controlled trial is justified to
      test this therapy especially in patients predicted to have a poor prognosis.

PMID- 14974031
TI  - Community pharmacy personnel interventions for smoking cessation.
AB  - BACKGROUND: Smoking cessation is a potentially appropriate role for community
      pharmacists because they are encouraged to advise on the correct use of nicotine
      replacement therapy (NRT) products and to provide behavioural support to aid
      smoking cessation. OBJECTIVES: This review assessed the effectiveness of
      interventions by community pharmacy personnel to assist clients to stop smoking.
      SEARCH STRATEGY: A search was made of the Cochrane Tobacco Addiction Group
      database for smoking cessation studies conducted in the community pharmacy
      setting, using the search terms pharmacist* or pharmacy or pharmacies. Date of
      the most recent search: March 2003. SELECTION CRITERIA: Randomized trials which
      compared interventions by community pharmacy personnel to promote smoking
      cessation amongst their clients who were smokers compared to usual pharmacy
      support or any less intensive programme. The main outcome measure was smoking
      cessation rates at six months or more after the start of the intervention. DATA
      COLLECTION AND ANALYSIS: Data were extracted by one author and checked by the
      second, noting: the country of the trial, details of participant community
      pharmacies, method of subject recruitment, smoking behaviour and characteristics
      of participants on recruitment, method of randomization, description of the
      intervention and of any pharmacy personnel training, and the outcome measures.
      Methodological quality was assessed according to the extent to which the
      allocation to intervention or control was concealed. Because of the potentially
      important cluster effects, we also rated trials according to whether they checked
      for or adjusted for these but, in the absence of consensus on how to pool cluster
      level data, we adopted a narrative approach to synthesizing the data, rather than
      a formal meta-analysis. MAIN RESULTS: We identified two trials which met our
      selection criteria. They included a total of 976 smokers. Both trials were set in
      the UK and involved a training intervention which included the Stages of Change
      Model; they then compared a support programme involving counselling and record
      keeping against a control receiving usual pharmacy support. In both studies a
      high proportion of intervention and control participants began using NRT. Both
      studies reported smoking cessation outcomes at three time points. However, the
      follow-up points were not identical (three, six and 12 months in one, and one,
      four and nine months in the other), and the trend in abstinence over time was not
      linear in either study, so the data could not be combined. One study showed a
      significant difference in self-reported cessation rates at 12 months: 14.3%
      versus 2.7% (p < 0.001); the other study showed a positive trend at each follow
      up with 12.0% versus 7.4% (p = 0.09) at nine months. REVIEWER'S CONCLUSIONS: The
      limited number of studies to date suggests that trained community pharmacists,
      providing a counselling and record keeping support programme for their customers,
      may have a positive effect on smoking cessation rates. The strength of evidence
      is limited because only one of the trials showed a statistically significant
      effect.

PMID- 14974032
TI  - Anticholinergics for neuroleptic-induced acute akathisia.
AB  - BACKGROUND: Neuroleptic-induced akathisia is one of the most common and
      distressing early-onset adverse effects of conventional antipsychotic drugs,
      being associated with poor compliance with treatment, and thus, ultimately, with
      an increased risk of relapse. This review assesses the role of anticholinergic
      drugs as an adjunct to standard antipsychotic medication in the pharmacological
      treatment of this problem. OBJECTIVES: To determine the clinical effects of
      anticholinergic drugs for neuroleptic-induced acute akathisia. SEARCH STRATEGY:
      The reviewers undertook electronic searches of Biological Abstracts (1982-1999),
      CINAHL (1982-1999), Cochrane Library (Issue 4 1999), Cochrane Schizophrenia
      Group's Register (October 1999), EMBASE (1980-1999), LILACS (1982-1999), MEDLINE
      (1966-1999) and PsycLIT (1974-1999). References of all identified studies were
      inspected for more trials and first authors contacted. Each included study was
      sought as a citation on the Science Citation Index database. SELECTION CRITERIA:
      All randomised clinical trials of anticholinergic drugs versus placebo for people
      with neuroleptic-induced acute akathisia. DATA COLLECTION AND ANALYSIS: Two
      reviewers, working independently, selected, quality assessed and extracted data.
      These data were then analysed on an intention-to-treat basis. For homogeneous
      dichotomous data the fixed effects relative risk (RR), the 95% confidence
      intervals (CI) and, where appropriate, the number needed to treat (NNT) were
      calculated on an intention-to-treat basis. For continuous data, reviewers
      calculated weighted mean differences. MAIN RESULTS: No randomised controlled
      trials could be included. REVIEWER'S CONCLUSIONS: At present, there is no
      reliable evidence to support or refute the use of anticholinergics for people
      suffering from neuroleptic-induced acute akathisia. Akathisia is a most
      distressing movement disorder that remains highly prevalent, both in the
      developed and developing world. This review highlights the need for well
      designed, conducted and reported clinical trials to address the claims of open
      studies as regards the effects of the anticholinergic group of drugs for
      akathisia.

PMID- 14974033
TI  - Type of incision for below knee amputation.
AB  - BACKGROUND: Below knee amputation (BKA) may be necessary in patients with
      advanced critical limb ischaemia or diabetic foot sepsis in whom no other
      treatment option is available. There is no consensus as to which surgical
      technique achieves the maximum rehabilitation potential. OBJECTIVES: To look at
      the evidence comparing different surgical techniques for BKA using stump healing,
      wound infection, reamputation rate and mobility with a prosthetic limb as outcome
      measures. SEARCH STRATEGY: Publications describing randomised controlled trials
      comparing different types of incision for below knee amputation were sought using
      the search strategy described by the Cochrane Review Group on Peripheral Vascular
      Diseases. This involved searching the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE and EMBASE. Additional searches were made of
      bibliographies of papers found through these searches, and also by handsearching
      relevant journals. SELECTION CRITERIA: Randomised controlled trials comparing two
      or more types of skin incision for BKA were identified. All patients with lower
      limb ischaemia (acute or chronic) and/or diabetic foot sepsis were considered for
      inclusion. Patients undergoing below knee amputation for other conditions were
      excluded. DATA COLLECTION AND ANALYSIS: Three studies were included in the
      analysis: two-stage versus one-stage BKA; skew flaps BKA versus long posterior
      flap BKA; sagittal flaps BKA versus long posterior flap BKA. Data were extracted
      independently by both authors. MAIN RESULTS: BKA using skew flaps or sagittal
      flaps conferred no advantage over the well established long posterior flap
      technique. For patients with wet gangrene, a two-stage procedure with a
      guillotine amputation at the ankle followed by a definitive long posterior flap
      amputation leads to better primary stump healing than a one-stage procedure.
      REVIEWER'S CONCLUSIONS: Evidence suggests that the choice of amputation technique
      has no effect on outcome and can therefore be a simple matter of surgeon
      preference. Factors which might influence this include previous experience of a
      particular technique, the extent of non-viable tissue, and the location of pre
      existing surgical scars.

PMID- 14974034
TI  - Albendazole for lymphatic filariasis.
AB  - BACKGROUND: Mass treatment with albendazole, co-administered with another
      antifilarial drug, is being promoted as part of a global programme to eliminate
      lymphatic filariasis. OBJECTIVES: To assess the effects of albendazole on
      patients or populations with filarial infection, and on morbidity in patients
      with filarial infection; and to assess the frequency of adverse events for
      albendazole both given singly or in combination with another antifilarial drug
      (diethylcarbamazine or ivermectin). SEARCH STRATEGY: We searched the Cochrane
      Infectious Disease Group's trial register (September 2003), the Cochrane Central
      Register of Controlled Trials (The Cochrane Library Issue 3, 2003), MEDLINE
      (September 2003), EMBASE (September 2003), LILACS (September 2003); and checked
      the reference lists and contacted experts, international organizations, and a
      pharmaceutical company. SELECTION CRITERIA: Randomized and quasi-randomized
      controlled trials of albendazole singly or in combination with anti-filarial
      drugs in people or populations with lymphatic filariasis. DATA COLLECTION AND
      ANALYSIS: Two reviewers assessed eligibility and trial methodological quality. We
      calculated relative risks (RR) with 95% confidence intervals (CI) for binary
      outcomes, and where appropriate, combined them in a meta-analysis using the fixed
      effect model or random effects model. MAIN RESULTS: Four small studies met the
      inclusion criteria (a total of 2473 children and adults, of whom 536 had
      detectable microfilariae). No effect of albendazole on microfilaraemia was
      demonstrated in two studies (placebo controlled, RR 0.97, 95%CI 0.87 to 1.09, n =
      195). When compared to ivermectin, albendazole performed worse (RR 0.84, 95% CI
      0.72 to 0.98, 2 studies of patients initially microfilariae positive, n = 198).
      When compared to diethylcarbamazine, no statistically significant difference was
      detected, but numbers were small (n = 56). Two studies compared albendazole plus
      ivermectin to ivermectin alone on the presence of microfilaraemia. Results were
      mixed: one study showed the combination to be more effective (RR 0.27, 95% CI
      0.11 to 0.70, n = 52), but the other did not demonstrate a statistically
      significant difference (RR 1.04, 95% CI 0.87 to 1.25, n = 145). A further study
      compared albendazole plus diethylcarbamazine to diethylcarbamazine alone and did
      not demonstrate a difference on microfilaraemia prevalence (RR 1.57, 95% CI 0.44
      to 5.60, n=35). No study examined the effects of the drugs on adult worms.
      REVIEWER'S CONCLUSIONS: There is insufficient reliable research to confirm or
      refute whether albendazole alone, or co-administered with diethylcarbamazine or
      ivermectin, has an effect on lymphatic filariasis.

PMID- 14974035
TI  - Antibiotics for preventing infection in open limb fractures.
AB  - BACKGROUND: Wound and bone infections are frequently associated with open
      fractures of the extremities and may add significantly to the resulting
      morbidity. The administration of antibiotics is routinely used in developed
      countries as an adjunct to a comprehensive management protocol that also includes
      irrigation, surgical debridement and stabilisation when indicated, and is thought
      to reduce the frequency of infections. OBJECTIVES: To quantify the evidence for
      the effectiveness of antibiotics in the initial treatment of open fractures of
      the limbs. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries
      Group specialised register (April 2003), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library issue 1, 2003), MEDLINE (1966 to April
      2003), EMBASE (1988 to April 2003), LILACS (1992 to June 2002) and reference
      lists of articles. Proceedings of meetings of the American Academy of Orthopaedic
      Surgeons (1980 to 2001), the Orthopaedic Trauma Association (1990 to 2001) and
      the Societe Internationale de Chirurgie Orthopedique et Traumatologique (1980 to
      2001) were hand searched. We also contacted published researchers in the field.
      SELECTION CRITERIA: Randomised or quasi-randomised controlled trials involving:
      participants - people of any age with open fractures of the limbs; intervention -
      antibiotic administered before or at the time of primary treatment of the open
      fracture compared with placebo or no antibiotic; outcome measures - early wound
      infection, chronic drainage, acute or chronic osteomyelitis, delayed unions or
      non-unions, amputations and deaths. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently screened papers for inclusion, assessed trial quality using an
      eight item scale, and extracted data. Additional information was sought from
      three trialists. Pooled data are presented graphically. MAIN RESULTS: Data from
      913 participants in seven studies were analysed. The use of antibiotics had a
      protective effect against early infection compared with no antibiotics or placebo
      (relative risk 0.41 (95% confidence interval (CI) 0.27 to 0.63); absolute risk
      reduction 0.08 (95% CI 0.04 to 0.12); NNT 13 (95% CI 8 to 25)). There were
      insufficient data in the included studies to evaluate other outcomes. REVIEWER'S
      CONCLUSIONS: Antibiotics reduce the incidence of early infections in open
      fractures of the limbs. Further placebo controlled randomised trials are unlikely
      to be justified in middle and high income countries. Further research is
      necessary to the determine the avoidable burden of morbidity in countries where
      antibiotics are not used routinely in the management of open fractures.

PMID- 14974036
TI  - Antibiotics for ureaplasma in the vagina in pregnancy.
AB  - BACKGROUND: Preterm birth is a significant obstetric problem in high-income
      countries. Genital infection including ureaplasmas are suspected of playing a
      role in preterm birth and preterm rupture of the membranes. Antibiotics are used
      to treat women with preterm prelabour rupture of the membranes and results in
      prolongation of pregnancy and lowers the risks of maternal and neonatal
      infection. However, antibiotics may be beneficial earlier in pregnancy to
      eradicate potentially causative agents. OBJECTIVES: The objective of this review
      is to assess whether antibiotic treatment of pregnant women with ureaplasma in
      the vagina reduces the incidence of preterm birth and other adverse pregnancy
      outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth
      Group trials register (April 2003). SELECTION CRITERIA: All randomised controlled
      trials that compared any antibiotic regimen with placebo or no treatment in
      pregnant women with ureaplasma detected in the vagina. DATA COLLECTION AND
      ANALYSIS: Three reviewers independently assessed eligibility and trial quality
      and extracted data. MAIN RESULTS: One trial involving 1071 women was included. Of
      these, 644 randomly received antibiotic treatment (174 erythromycin estolate, 224
      erythromycin sterate, and 246 clindamycin hydrochloride) and 427 received
      placebo. This trial did not report data on preterm birth. Incidence of low
      birthweight less than 2500 grams was only evaluated for erythromycin (combined)
      (n = 398 ) compared to placebo (n = 427) and there was no statistically
      significant difference between those treated and those not treated (relative risk
      (RR) 0.70, 95% confidence interval (CI) 0.46 to 1.07). In regards to side-effects
      sufficient to stop treatment, data were available for all women, and there were
      no statistically significant differences between any antibiotic (combined) and
      the placebo group (RR 1.25, 95% CI 0.85 to 1.85). REVIEWER'S CONCLUSIONS: There
      is insufficient evidence to show whether giving antibiotics to women with
      ureaplasma in the vagina will prevent preterm birth.

PMID- 14974037
TI  - Paracetamol versus nonsteroidal anti-inflammatory drugs for rheumatoid arthritis.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are usually preferred
      for simple analgesics such as paracetamol for rheumatoid arthritis. It is not
      clear, however, whether the trade-offs between benefits and harms of NSAIDs are
      preferable to those of paracetamol (paracetamol is also called acetaminophen).
      OBJECTIVES: To compare the benefits and harms of paracetamol with NSAIDs in
      patients with rheumatoid arthritis. SEARCH STRATEGY: Medline Silverplatter,
      Embase databases were searched up until Sept 2002. Reference lists of identified
      articles were also searched. SELECTION CRITERIA: Randomised double-blind studies
      comparing paracetamol with an NSAID. DATA COLLECTION AND ANALYSIS: Decisions on
      inclusion of trials and data extraction were performed by the two authors
      independently. MAIN RESULTS: Four cross-over studies, published between 1968 and
      1982, involving 121 patients, and four different NSAIDs were included. The
      generation of the allocation sequence and the use of methods to conceal the
      allocation were not described in any of the studies. The studies were double
      blind but it was not clear whether the blinding was effective. Methods for
      collecting adverse effects were not described. The NSAIDs were preferred more
      often than paracetamol by the patients or the investigator. In the largest trial,
      20 out of 54 patients (37%) preferred ibuprofen and 7 out of 54 (13%)
      paracetamol. Investigators preference (as established by joint tenderness, grip
      strength and joint circumference) was 17 out of 35 for diclofenac versus 5 out of
      35 for paracetamol in another trial. However, because of the weaknessess in the
      trials, no firm conclusion can be drawn. REVIEWER'S CONCLUSIONS: When considering
      the trade off between the benefits and harms of non-steroidal anti-inflammatory
      drugs and paracetamol/acetaminophen, it is not known whether one is better than
      the other for rheumatoid arthritis. But people with rheumatoid arthritis and the
      researchers in the study did prefer non-steroidal anti-inflammatory drugs more
      than acetaminophen/paracetamol. There is a need for a large trial, with
      appropriate randomisation, double-blinding, test of the success of the blinding,
      and with explicit methods to measure and analyse pain and adverse effects.

PMID- 14974038
TI  - Specialist outreach clinics in primary care and rural hospital settings.
AB  - BACKGROUND: Specialist medical practitioners have conducted clinics in primary
      care and rural hospital settings for a variety of reasons in many different
      countries. Such clinics have been regarded as an important policy option for
      increasing the accessibility and effectiveness of specialist services and their
      integration with primary care services. OBJECTIVES: To undertake a descriptive
      overview of studies of specialist outreach clinics and to assess the
      effectiveness of specialist outreach clinics on access, quality, health outcomes,
      patient satisfaction, use of services, and costs. SEARCH STRATEGY: We searched
      the Cochrane Effective Practice and Organisation of Care (EPOC) specialised
      register (March 2002), the Cochrane Controlled Trials Register (CCTR) (Cochrane
      Library Issue 1, 2002), MEDLINE (including HealthStar) (1966 to May 2002), EMBASE
      (1988 to March 2002), CINAHL (1982 to March 2002), the Primary-Secondary Care
      Database previously maintained by the Centre for Primary Care Research in the
      Department of General Practice at the University of Manchester, a collection of
      studies from the UK collated in "Specialist Outreach Clinics in General Practice"
      (Roland 1998), and the reference lists of all retrieved articles. SELECTION
      CRITERIA: Randomised trials, controlled before and after studies and interrupted
      time series analyses of visiting specialist outreach clinics in primary care or
      rural hospital settings, either providing simple consultations or as part of
      complex multifaceted interventions. The participants were patients, specialists,
      and primary care providers. The outcomes included objective measures of access,
      quality, health outcomes, satisfaction, service use, and cost. DATA COLLECTION
      AND ANALYSIS: Four reviewers working in pairs independently extracted data and
      assessed study quality. MAIN RESULTS: 73 outreach interventions were identified
      covering many specialties, countries and settings. Nine studies met the inclusion
      criteria. Most comparative studies came from urban non-disadvantaged populations
      in developed countries. Simple 'shifted outpatients' styles of specialist
      outreach were shown to improve access, but there was no evidence of impact on
      health outcomes. Specialist outreach as part of more complex multifaceted
      interventions involving collaboration with primary care, education or other
      services was associated with improved health outcomes, more efficient and
      guideline-consistent care, and less use of inpatient services. The additional
      costs of outreach may be balanced by improved health outcomes. REVIEWER'S
      CONCLUSIONS: This review supports the hypothesis that specialist outreach can
      improve access, outcomes and service use, especially when delivered as part of a
      multifaceted intervention. The benefits of simple outreach models in urban non
      disadvantaged settings seem small. There is a need for good comparative studies
      of outreach in rural and disadvantaged settings where outreach may confer most
      benefit to access and health outcomes.

PMID- 14974039
TI  - Posterior versus lateral surgical approach for total hip arthroplasty in adults
      with osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) of the hip is a progressive condition that has no
      cure and often requires a total hip arthroplasty (THA). The principal methods for
      THA are the posterior and direct lateral approaches. The posterior approach is
      considered to be easy to perform, however, increased rates of dislocation have
      been reported. The direct lateral approach facilitates cup positioning which may
      decrease rates of hip dislocation and diminishes the risk of injury to the
      sciatic nerve. However, there is an increased risk of limp. Dislocation of a hip
      prosthesis is a clinically important complication after THA, in terms of
      morbidity implications and costs. OBJECTIVES: To determine the risks of
      prosthesis dislocation, postoperative Trendelenburg gait and sciatic nerve palsy
      after a posterior approach, compared to a direct lateral approach, for adult
      patients undergoing THA for primary OA. SEARCH STRATEGY: MEDLINE, EMBASE, CINHAL
      and Cochrane databases were searched until 2002. No language restrictions were
      applied. SELECTION CRITERIA: Published trials comparing posterior and direct
      lateral surgical approaches to THA in participants 18 years and older with a
      diagnosis of primary hip OA. DATA COLLECTION AND ANALYSIS: Retrieved articles
      were assessed independently by the two reviewers for their methodological
      quality. MAIN RESULTS: Four prospective cohort studies involving 241 participants
      met the inclusion criteria. The primary outcome, dislocation, was reported in two
      studies. No significant difference between posterior and direct lateral surgical
      approach was found [1/77 (1.3%) versus 3/72 (4.2%); relative risk (RR) 0.35; 95%
      confidence intervals (CI) 0.04 to 3.22]. The presence of postoperative
      Trendelenburg gait was not significantly different between these surgical
      approaches. The risk of nerve palsy or injury was significantly higher among the
      direct lateral approaches [1/43 (2%) versus 10/49 (20%); RR 0.16, 95% CI 0.03 to
      0.83]. However, there were no significant differences when comparing this risk
      nerve by nerve for both approaches, in particular for the sciatic nerve. Of the
      other outcomes considered only the average range of internal rotation in
      extension of the hip was significantly higher (weighted mean difference 16
      degrees, 95% CI 8 to 23) in the posterior approach group (mean 35 degrees,
      standard deviation 13 degrees ) compared to the direct lateral approach (mean 19
      degrees, standard deviation 13 degrees ). REVIEWER'S CONCLUSIONS: The quality and
      quantity of information extracted from the trials performed to date are
      insufficient to make any firm conclusion on the optimum choice of surgical
      approach in adult patients undergoing primary THA for OA.

PMID- 14974040
TI  - Prophylactic intravenous antifungal agents to prevent mortality and morbidity in
      very low birth weight infants.
AB  - BACKGROUND: Invasive fungal infection is an increasingly common cause of
      mortality and morbidity in very low birth weight infants. As the diagnosis is
      often difficult, and treatment is often delayed, there is a need to assess
      whether antifungal prophylaxis is beneficial. OBJECTIVES: To assess whether
      prophylactic intravenous antifungal therapy reduces mortality and adverse
      neurodevelopmental outcomes in very low birth weight infants. SEARCH STRATEGY: We
      used the standard search strategy of the Cochrane Neonatal Review Group. This
      included searches of the Cochrane Central Register of Controlled Trials (CENTRAL,
      The Cochrane Library, Issue 4, 2003), MEDLINE (1966 - October 2003), EMBASE (1980
      - October 2003), conference proceedings, and previous reviews. SELECTION
      CRITERIA: Randomised controlled trials that compared the effect of prophylactic
      intravenous antifungal therapy versus placebo, or no drug, or another antifungal
      agent, in very low birth weight infants. DATA COLLECTION AND ANALYSIS: We
      extracted the data using the standard methods of the Cochrane Neonatal Review
      Group, with separate evaluation of trial quality and data extraction by each
      author, and synthesis of data using relative risk and risk difference. The pre
      specified outcomes were death prior to hospital discharge, longer term
      neurodevelopment, incidence of invasive fungal infection, emergence of antifungal
      resistance, and adverse drug reactions. MAIN RESULTS: We identified three
      eligible trials enrolling a total of 214 infants. Each of the trials compared the
      effect of prophylactic intravenous fluconazole versus placebo. Two of the trials
      reported death prior to hospital discharge as an outcome. 29 of the 203 infants
      recruited to these studies died. Meta-analysis revealed a statistically
      significantly reduced risk of death prior to hospital discharge for the infants
      who received fluconazole prophylaxis: typical relative risk: 0.44 (95% confidence
      interval 0.21, 0.91); typical risk difference: -0.11 (95% confidence interval 
      0.21, -0.02); number needed to treat: 9 (95% confidence interval 5, 50). None of
      the trials reported data on longer term outcomes. REVIEWER'S CONCLUSIONS: We have
      found some evidence that prophylactic intravenous fluconazole reduces mortality
      prior to hospital discharge in very low birth weight infants. The meta-analysis
      suggests that there will be one fewer death in every nine infants treated with
      this intervention, but the 95% confidence interval around this estimate of effect
      is wide. The longer term neurodevelopmental consequences for infants exposed to
      this intervention remain to be determined. It will be important to identify any
      subgroups of very low birth weight infants that receive the most benefit from
      this intervention. There is also a need for further data on the effect of the
      intervention on the emergence of organisms with stable antifungal resistance.

PMID- 14974041
TI  - Information for pregnant women about caesarean birth.
AB  - BACKGROUND: Information is routinely given to pregnant women, but information
      about caesarean birth may be inadequate. OBJECTIVES: To examine the effectiveness
      of information about caesarean birth. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth register, CENTRAL (26 November 2002), MEDLINE [online
      via PubMed 1966-] and the Web of Science citation database [1995-] (20 September
      2002), and reference lists of relevant articles. SELECTION CRITERIA: Randomised
      controlled trials, non-randomised clinical trials and controlled before-and-after
      studies of information given to pregnant women about caesarean birth. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and
      extracted data. Missing and further data were sought from trial authors
      unsuccessfully. Analyses were based on 'intention to treat'. Relative risk and
      confidence intervals were calculated and reported. Consumer reviewers commented
      on adequacy of information reported in each study. MAIN RESULTS: Two randomised
      controlled trials involving 1451 women met the inclusion criteria. Both studies
      aimed to reduce caesarean births by encouraging women to attempt vaginal
      delivery. One used a program of prenatal education and support, and the other
      cognitive therapy to reduce fear. Results were not combined because of
      differences in the study populations. Non-clinical outcomes were ascertained in
      both studies through questionnaires, but were subject to rates of loss to follow
      up exceeding 10%.A number of important outcomes cannot be reported: knowledge or
      understanding; decisional conflict; and women's perceptions: of their ability to
      discuss care with clinicians or family/friends, of whether information needs were
      met, and of satisfaction with decision-making. Neither study assessed women's
      perception of participation in decision-making about caesarean birth, but Fraser
      1997, who examined the effect of study participation on decision making, found
      that women in the intervention group were more likely to consider that attempting
      vaginal birth was easier (51% compared to 28% in control group), or more
      difficult (10% compared to 6%). These results could be affected by the attrition
      rate of 11%, and are possibly subject to bias. Neither intervention used in these
      trials made any difference to clinical outcomes. About 70% or more women
      attempted vaginal delivery in both trials, yet caesarean delivery rates exceeded
      40%, at least 10% higher than was hoped. There was no significant difference
      between control and intervention groups for any of the outcomes measured: vaginal
      birth, elective/scheduled caesarean, and attempted vaginal delivery. Outcome
      data, although similar for both groups, were not sufficient to compare maternal
      and neonatal morbidity or neonatal mortality. There was no difference in the
      psychological outcomes for the intervention and control groups reported by either
      of the included trials. Consumer reviewers said information for women considering
      a vaginal birth after caesarean (VBAC) should include: risks of VBAC and elective
      caesarean; warning signs in labour; philosophy and policies of hospital and
      staff; strategies to improve chances of success; and information about
      probability of success with specific care givers. REVIEWER'S CONCLUSIONS:
      Research has focussed on encouraging women to attempt vaginal delivery. Trials of
      interventions to encourage women to attempt vaginal birth showed no effect, but
      shortcomings in study design mean that the evidence is inconclusive. Further
      research on this topic is urgently needed.

PMID- 14974042
TI  - Pneumococcal vaccines for sickle cell disease.
AB  - BACKGROUND: People with sickle cell disease are particularly susceptible to
      pneumococcal infection, which may be fatal. Infants (children aged up to 23
      months) are at particularly high risk, but conventional polysaccharide
      pneumococcal vaccines may be ineffective in this age group. New conjugate
      pneumococcal vaccines are now available, which may help to reduce the incidence
      of infection in people with sickle cell disease. OBJECTIVES: To determine the
      efficacy of pneumococcal vaccines for reducing morbidity and mortality in people
      with sickle cell disease. SEARCH STRATEGY: We searched the Cochrane Cystic
      Fibrosis and Genetic Disorders Group trials register, comprising of references
      identified from comprehensive electronic database searches and hand searching
      relevant journals and abstract books of conference proceedings. In addition, we
      contacted relevant pharmaceutical companies and experts in the field.Date of most
      recent search of Group's trials register: November 2003. SELECTION CRITERIA: All
      randomised and quasi-randomised controlled trials comparing a polysaccharide or
      conjugate pneumococcal vaccine regimen with a different regimen or no vaccination
      in people with sickle cell disease. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently selected studies for inclusion, extracted data and assessed trial
      quality. MAIN RESULTS: Nine trials were identified in the searches and five
      trials, with a total of 547 participants, met the inclusion criteria. Only one
      trial reported incidence of pneumococcal infection, and this demonstrated that
      the polysaccharide pneumococcal vaccine used (PPV14) failed to significantly
      reduce the risk of infection in children under three years of age, but was
      associated with only minor adverse events. Three trials of conjugate pneumococcal
      vaccines found that immune response was increased compared to control groups,
      including in infants, although clinical outcomes were not measured in these
      trials. REVIEWER'S CONCLUSIONS: Previous trials have shown that conjugate
      pneumococcal vaccines are safe and effective in normal healthy patients, even
      those under the age of two years. The controlled trials included in this review
      have demonstrated immunogenicity (the body's response, without which there is no
      protection) of these vaccines, and observational studies in people with sickle
      cell disease support these findings. We therefore recommend that conjugate
      pneumococcal vaccines are used in people with sickle cell disease. Randomised
      trials in patients with sickle cell disease will be needed to determine the
      optimal vaccination regimen when further, potentially more effective vaccines
      become available. Such trials should measure clinical outcomes of effectiveness.

PMID- 14974043
TI  - Interleukin 2 receptor antagonists for kidney transplant recipients.
AB  - BACKGROUND: Interleukin 2 receptor antagonists (IL2Ra) are used as induction
      therapy for prophylaxis against acute rejection in kidney transplant recipients.
      Use of IL2Ra has increased steadily, with 38% of new kidney transplant recipients
      in the United States, and 23% in Australasia receiving IL2Ra in 2002. OBJECTIVES:
      This study aims to systematically identify and summarise the effects of using an
      IL2Ra, as an addition to standard therapy, or as an alternative to other antibody
      therapy. SEARCH STRATEGY: The Cochrane Renal Group's specialised register (June
      2003), the Cochrane Controlled Trials Register (in The Cochrane Library issue 3,
      2002), MEDLINE (1966-November 2002) and EMBASE (1980-November 2002). Reference
      lists and abstracts of conference proceedings and scientific meetings were hand
      searched from 1998-2003. Trial groups, authors of included reports and drug
      manufacturers were contacted. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) in all languages comparing IL2Ra to placebo, no treatment, other IL2Ra or
      other antibody therapy. DATA COLLECTION AND ANALYSIS: Data was extracted and
      quality assessed independently by two reviewers, with differences resolved by
      discussion. Dichotomous outcomes are reported as relative risk (RR) with 95%
      confidence intervals (CI). MAIN RESULTS: One hundred and seventeen reports from
      38 trials involving 4893 participants were included. Where IL2Ra were compared
      with placebo (17 trials; 2786 patients), graft loss was not significantly
      different at one (RR 0.83, 95% CI 0.66 to 1.04) or three years (RR 0.88, 95% CI
      0.64 to 1.22). Acute rejection (AR) was significantly reduced at six months (RR
      0.66, 95% CI 0.59 to 0.74) and at one year (RR 0.67, 95% CI 0.60 to 0.75). At one
      year, cytomegalovirus (CMV) infection (RR 0.82, 95% CI 0.65 to 1.03) and
      malignancy (RR 0.67, 95% CI 0.33 to 1.36) were not significantly different. Where
      IL2Ra were compared with other antibody therapy no significant differences in
      treatment effects were demonstrated, but adverse effects strongly favoured IL2Ra.
      REVIEWER'S CONCLUSIONS: Given a 40% risk of rejection, seven patients would need
      treatment with IL2Ra to prevent one patient having rejection, with no definite
      improvement in graft or patient survival. There is no apparent difference between
      basiliximab and daclizumab. IL2Ra are as effective as other antibody therapies
      and with significantly fewer side effects

PMID- 14974044
TI  - Concomitant hydroxyurea plus radiotherapy versus radiotherapy for carcinoma of
      the uterine cervix.
AB  - BACKGROUND: A number of randomised studies suggest hydroxyurea given alongside
      radiotherapy improves survival in patients with locally advanced cervix cancer.
      Following publication of five large randomised trials in 1999 and 2000
      concomitant chemoradiotherapy has become standard treatment for these patients.
      In two of the studies hydroxyurea was given to patients in both control and
      experimental arms. The precise role of this orally administered cytotoxic drug is
      not known. OBJECTIVES: To assess the effectiveness (survival and toxicity) of
      concomitant radiation and hydroxyurea compared with radiotherapy alone in
      treating locally advanced cervix cancer. SEARCH STRATEGY: We searched the
      following:Cochrane Gynaecological Cancer Group's Specialised RegisterCENTRAL
      (Cochrane Library on CD ROM, issue 4, 2002) MEDLINE (Silver Platter, from 1970 to
      2001) EMBASE (from 1980 to 2001) CANCERLIT (from 1970 to 2001) PDQ (search for
      open and closed trials) LILACSMeta-register (ongoing trials)Searches were not
      language or publication restricted. Investigators of relevant trials were
      contacted for further information. SELECTION CRITERIA: Randomized controlled
      trials comparing concomitant radiotherapy (+/- surgery) with hydroxyurea versus
      radiotherapy (+/- surgery) for locally advanced cervix cancer. DATA COLLECTION
      AND ANALYSIS: Two authors independently reviewed trials for inclusion and
      extracted data. Discussions on all aspects of data collection and analysis took
      place among all the authors at regular intervals. MAIN RESULTS: Seven studies
      were found to be suitable for inclusion from 33 identified as relevant. None of
      the trials provided adequate evidence to support the use of hydroxyurea owing to
      small sample size, large numbers of post-randomisation exclusions and
      questionable rules for censoring, particularly a failure to include treatment
      related deaths in the survival analysis. Details of statistical analysis were
      limited and often confusing, and we felt meta-analysis would lead to unreliable
      and invalid conclusions. Most studies appeared to be double blind placebo
      controlled studies but none give details of power calculations or reasons for
      stopping recruitment. Only two studies had more than 50 patients. Patients were
      excluded from analysis in most trials for treatment-related reasons; in one, less
      than half those recruited were used in the analysis, the remainder having been
      excluded because of tumour progression or treatment-related conditions e.g.
      septicaemia, worsening renal/hepatic function. In another trial five out of 20 in
      the hydroxyurea group died of treatment-related complications but the five-year
      survival group was presented as 94%. REVIEWER'S CONCLUSIONS: We found no evidence
      to support the use of hydroxyurea in addition to radiotherapy in the routine
      treatment of cervix cancer.

PMID- 14974045
TI  - Systemic antifungal drugs for invasive fungal infection in preterm infants.
AB  - BACKGROUND: Invasive fungal infection is an increasingly common cause of
      mortality and morbidity in preterm infants. In addition to amphotericin B, a
      variety of newer antifungal drugs and drug preparations are available for
      treatment. There is a need to assess their relative merits. OBJECTIVES: In
      preterm infants with suspected or confirmed invasive fungal infection, does
      treatment with newer systemic antifungal drugs or drug preparations, versus
      conventional amphotericin B alone, reduce mortality and adverse
      neurodevelopmental outcomes? SEARCH STRATEGY: We used the standard search
      strategy of the Cochrane Neonatal Review Group. This included searches of the
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library,
      Issue 3, 2003), MEDLINE (1966 - August 2003), EMBASE (1980 - August 2003),
      conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised and
      quasi-randomised control trials comparing one antifungal agent or combination of
      agents with another in preterm infants with suspected or confirmed invasive
      fungal infection. DATA COLLECTION AND ANALYSIS: We extracted the data using the
      standard methods of the Cochrane Neonatal Review Group, with separate evaluation
      of trial quality and data extraction by each author, and synthesis of data using
      relative risk and risk difference. The pre-specified outcomes were death prior to
      hospital discharge, longer term neurodevelopment, and adverse drug reactions
      resulting in discontinuation of therapy. MAIN RESULTS: We identified only one
      small trial. This study compared the use of fluconazole with amphotericin B (5
      Fluorocytosine added if fungal meningitis present). Three of 11 infants who were
      treated with fluconazole died and four of 10 infants who were treated with
      amphotericin B died : Relative risk: 0.68 (95% confidence interval 0.20, 2.33),
      Risk Difference -0.13 (95% confidence interval -0.53, 0.27) There were not any
      data on longer term outcomes. REVIEWER'S CONCLUSIONS: From this one small study
      there are insufficient data to favour one antifungal agent or combination to
      reduce mortality and adverse neurodevelopmental outcomes in preterm infants with
      suspected or confirmed invasive fungal infection. A large randomised controlled
      trial is required to compare the newer antifungal preparations with conventional
      amphotericin B. Further research may also determine the relative convenience and
      cost effectiveness of the available drugs.

PMID- 14974046
TI  - Diazepam for treating tetanus.
AB  - BACKGROUND: Clinical management of the muscle spasms and rigidity of tetanus
      poses a difficult therapeutic problem to physicians everywhere, especially in
      resource poor countries. There are wide variations in therapeutic regimens
      commonly used in clinical practice due to uncertainties about effectiveness of
      conventional drugs. Diazepam compared to other drugs (eg phenobarbitone and
      chlorpromazine) may have advantages because of combined anticonvulsant, muscle
      relaxant, sedative and anxiolytic effects. OBJECTIVES: To compare diazepam to
      other drugs in treating the muscle spasms and rigidity of tetanus in children and
      adults. SEARCH STRATEGY: We searched the Cochrane Neonatal Group trials register
      (October 2003), Cochrane Central Register of Controlled Trials (The Cochrane
      Library, Issue 3, 2003), MEDLINE (1966 to October 2003), EMBASE (1980 to October
      2003), LILACS (2003), CINAHL (October 2003), Science Citation Index, African
      Index Medicus, conference abstracts and reference lists of articles. We contacted
      researchers, experts and organizations working in the field and used personal
      communication. SELECTION CRITERIA: Randomized and quasi-randomized controlled
      trials. DATA COLLECTION AND ANALYSIS: We independently identified eligible
      trials, assessed trial methodological quality and extracted data. MAIN RESULTS:
      Two studies met the inclusion criteria. Method of generation of allocation
      sequence, concealment of allocation and blinding were unclear in both studies. A
      total of 134 children were allocated to three treatment groups comprising
      diazepam alone, phenobarbitone and chlorpromazine, or phenobarbitone and
      chlorpromazine and diazepam.Meta-analysis of in-hospital deaths indicates that
      children treated with diazepam alone had a better chance of survival than those
      treated with combination of phenobarbitone and chlorpromazine (Relative Risk for
      death 0.36; 95% confidence interval 0.15 to 0.86; Risk Difference -0.22; 95% CI 
      0.38 to -0.06). Giving diazepam alone, or supplementing conventional
      anticonvulsants (phenobarbitone and chlorpromazine) with diazepam, was reported
      in one study to be associated with a statistically significantly milder clinical
      course and shorter duration of hospitalization. REVIEWER'S CONCLUSIONS: Although
      there is evidence that diazepam alone compared with combination of phenobarbitone
      and chlorpromazine is more effective in treating tetanus, the small size,
      methodological limitations and lack of data on drug safety from available trials
      preclude definite conclusions to support change in current clinical practice. The
      application of the present evidence should be moderated by local needs and
      circumstances, pending the availability of more evidence. We recommend a large
      multicenter, randomized controlled trial which compares diazepam alone with
      combinations of other drugs (excluding diazepam).

PMID- 14974047
TI  - Naloxone for preventing morbidity and mortality in newborn infants of greater
      than 34 weeks' gestation with suspected perinatal asphyxia.
AB  - BACKGROUND: Studies in animal models have suggested that naloxone, a specific
      opiate antagonist, may improve outcomes for newborn infants with perinatal
      asphyxia. OBJECTIVES: In newborn infants of greater than 34 weeks' gestation with
      suspected perinatal asphyxia: to assess the effects of naloxone versus placebo or
      no drug, and of single versus multiple doses of naloxone, on mortality, long term
      neurological problems, severity of hypoxic-ischaemic encephalopathy, and
      frequency of neonatal seizures. SEARCH STRATEGY: We used the standard search
      strategy of the Cochrane Neonatal Review Group. This included searches of the
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library,
      Issue 3, 2003), MEDLINE (1966 - August 2003), EMBASE (1980 - August 2003),
      conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised or
      quasi-randomised controlled trials comparing naloxone versus placebo, or no drug,
      or another dose of naloxone, in newborn infants of greater than 34 weeks'
      gestation with suspected perinatal asphyxia. DATA COLLECTION AND ANALYSIS: We
      extracted data using the standard methods of the Cochrane Neonatal Review Group,
      with separate evaluation of trial quality and data extraction by two authors. The
      pre-specified outcomes for this review were: death before hospital discharge,
      severe neurodevelopmental disability, severity of hypoxic-ischaemic
      encephalopathy, and seizures in the neonatal period. MAIN RESULTS: We identified
      only one eligible randomised controlled trial. This study compared the use of
      naloxone with placebo in newborn infants with an Apgar score of six or less at
      one minute after birth. There were not any data on the pre-specified outcomes for
      this review. REVIEWER'S CONCLUSIONS: There are insufficient data available to
      evaluate the safety and effectiveness of the routine use of naloxone for newborn
      infants of greater than 34 weeks' gestation with suspected perinatal asphyxia. A
      further randomised controlled trial is needed to determine if naloxone benefits
      newborn infants with suspected perinatal asphyxia. Such a trial should assess
      clinically important outcomes such as mortality, and adverse short and long term
      neurological outcomes.

PMID- 14974048
TI  - Adrenaline for prevention of morbidity and mortality in preterm infants with
      cardiovascular compromise.
AB  - BACKGROUND: Inotropes are widely used in preterm infants to treat cardiovascular
      compromise, which may result from early adaptive problems of the transitional
      circulation, perinatal asphyxia or sepsis. Sustained hypotension and poor organ
      blood flow are associated with brain injury including peri/intraventricular
      haemorrhage and subsequent poor neurodevelopmental outcomes. Adrenaline
      (epinephrine) infusions are used in preterm infants with clinical cardiovascular
      compromise. OBJECTIVES: To determine the effectiveness and safety of adrenaline
      compared to no treatment or other inotropes in reducing mortality and morbidity
      in preterm infants with cardiovascular compromise. SEARCH STRATEGY: Randomised
      controlled trials were identified by searching MEDLINE (1966-August 2003), The
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library,
      Issue 3, 2003) and EMBASE (1980 - 2003), supplemented with searches of reference
      lists of published trials and abstracts of conference proceedings. SELECTION
      CRITERIA: Randomised controlled trials of preterm newborn infants that compared
      adrenaline to no treatment or other inotropic agents (including dopamine,
      dobutamine, noradrenaline or isoprenaline). DATA COLLECTION AND ANALYSIS: Data
      were extracted and analysed independently by two reviewers. Treatment effects on
      the following outcomes were to be determined: mortality in the newborn period,
      long term neurodevelopmental outcomes, radiological evidence of brain injury,
      short term haemodynamic changes, adverse drug effects and short term neonatal
      outcomes. Study authors were contacted for additional information. Studies were
      analysed for methodological quality using the criteria of the Cochrane Neonatal
      Review Group. MAIN RESULTS: One ongoing study (Pellicer 2003) was identified. One
      study comparing adrenaline with dopamine infusion was included but was published
      in abstract form only (Phillipos 1996). It enrolled hypotensive, predominantly
      preterm infants in the first 24 hours. Only infants >1750g are included in this
      review (report for infants <=1750g appears incomplete). The study was reported as
      being randomised and double blinded, but methods were not reported. Both
      adrenaline and dopamine significantly increased heart rate and mean BP, with no
      statistically significant effect on left or right ventricular outputs. No other
      clinical outcomes were reported. No studies were identified that compared
      adrenaline to other inotropes, placebo or no treatment. REVIEWER'S CONCLUSIONS:
      There are insufficient data on the use of adrenaline infusions in preterm infants
      with cardiovascular compromise to make recommendations for practice. There is a
      need for larger trials to determine whether adrenaline is effective in reducing
      morbidity and mortality in preterm infants with cardiovascular compromise.

PMID- 14974049
TI  - Tegaserod for the treatment of irritable bowel syndrome.
AB  - BACKGROUND: IBS is a complex disorder that encompasses a wide profile of
      symptoms. Current drug treatments for irritable bowel syndrome (IBS) are of
      limited value. Many target specific symptoms only. Tegaserod, a 5HT(4) partial
      agonist, represents a novel mechanism of action in the treatment of IBS.
      OBJECTIVES: The objective of this review was to evaluate the efficacy and
      tolerability of tegaserod for the treatment of IBS in adults and adolescents aged
      12 years and above. SEARCH STRATEGY: MEDLINE 1966-November 2002 and EMBASE 1980
      November 2002 were searched. The text and key words used included "tegaserod",
      "HTF 919", "irritable bowel", and "colonic diseases, functional". The Cochrane
      Central Register of Controlled Trials, the Inflammatory Bowel Disease Review
      Group Specialized Trials Register, and Science Citation Index were also searched.
      Proceedings from the British Society of Gastroenterology Annual Meeting, and
      Digestive Disease Week (1998-2002) were hand searched. The manufacturer of
      tegaserod was contacted. Relevant articles were retrieved, and their reference
      lists were also reviewed. SELECTION CRITERIA: Randomised or quasi-randomised
      controlled trials comparing tegaserod with placebo, no treatment or any other
      intervention (pharmacological or non-pharmacological) in subjects aged 12 years
      and above with a diagnosis of IBS, focusing on clinical endpoints were considered
      for review. DATA COLLECTION AND ANALYSIS: Study inclusion and exclusion, data
      extraction and quality assessment was undertaken by two reviewers independently.
      Meta-analysis was performed where study populations, designs, outcomes, and
      statistical reporting allowed combination of data in a valid way, using the
      summary statistic relative risk with 95% CI. Eight short-term placebo-controlled
      studies fulfilled our inclusion criteria. These were predominantly conducted in
      women. Seven studies evaluated the efficacy of tegaserod on global
      gastrointestinal (GI) symptoms in patients with constipation-predominant IBS (C
      IBS). One small study evaluated safety in patients with diarrhoea-predominant
      IBS. MAIN RESULTS: The relative risk (RR) of being a responder in terms of global
      relief of GI symptoms was significantly higher with tegaserod 12 mg (RR 1.19, 95%
      CI 1.09, 1.29) and tegaserod 4 mg (RR 1.15, 95% CI 1.02, 1.31) compared with
      placebo, with a number needed to treat (NNT) of 14 and 20 respectively. When all
      tegaserod doses were combined and compared with placebo (n=4040), the RR of being
      a responder was 1.17 (95% CI 1.08, 1.27), with a NNT of 17. Although the pooled
      results indicate statistically significant benefit with tegaserod, the a priori
      minimal clinically important differences set in two of the four pooled studies
      were not reached. Tegaserod did not significantly improve the patients'
      individual symptoms of abdominal pain and discomfort although bowel habit showed
      a statistically significant improvement with tegaserod 4 mg and there was a non
      significant trend in favour of tegaserod 12 mg. When GI symptoms were assessed
      separately, those indicative of GI motility such as number of bowel movements and
      days without bowel movements were generally improved with tegaserod although the
      proportion of patients experiencing diarrhoea was significantly higher in the
      tegaserod 12 mg group compared with placebo (RR 2.75, 95% CI 1.90, 3.97), with a
      number needed to harm (NNH) of 20. Effects of tegaserod on GI symptoms such as
      bloating, stool consistency, and straining were not consistent across the
      studies. REVIEWER'S CONCLUSIONS: Tegaserod appears to improve the overall
      symptomatology of IBS but there are currently few data on its effect on quality
      of life. In addition, more information is needed about its efficacy in men. It
      would also be of interest to know whether treatment with tegaserod leads either
      directly, or indirectly, to changes in visceral sensitivity or psychopathology,
      which are also considered important in the pathophysiology of this condition.

PMID- 14974050
TI  - Prescription of prosthetic ankle-foot mechanisms after lower limb amputation.
AB  - BACKGROUND: A correct prosthetic prescription can be derived from adapting the
      functional benefits of a prosthesis to the functional needs of the prosthetic
      user. For adequate matching, the functional abilities of the amputees are of
      value, as well as the technical and functional aspects of the various prosthetic
      ankle-foot mechanisms. There seems to be no clear clinical consensus on the
      precise prescription criteria for the various prosthetic ankle-foot mechanisms
      related to the functional abilities of amputees. OBJECTIVES: To obtain
      information about aspects of prosthetic ankle-foot mechanisms and daily
      functioning of amputees with a prosthesis, for appropriate prosthetic
      prescription criteria. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal
      Injuries Group specialised register of trials (April 2003), the Cochrane Central
      Register of Controlled Trials (The Cochrane Library issue 1, 2003), MEDLINE (1966
      to April 2003), EMBASE (1983 to April 2003), CINAHL (1982 to April 2003) and
      reference lists of articles. No language restrictions were applied. SELECTION
      CRITERIA: All randomised controlled trials and quasi-randomised controlled trials
      comparing different prosthetic devices for lower limb amputation in adults. No
      language restrictions were applied. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently identified potential articles from the literature search.
      Methodological quality was assessed using a checklist comprising 13 criteria. The
      reviewers extracted data using pre-defined extraction forms. MAIN RESULTS: Twenty
      three trials were included, with a total of 217 participants. The methodological
      quality was moderate. Only one study was of high quality. No classical RCT's were
      identified, yet, all included studies used cross-over designs allowing sufficient
      control for confounding. In high activity transfemoral amputees, there is limited
      evidence for the superiority of the Flex foot during level walking compared with
      the SACH foot in respect of energy cost and, gait efficiency. This benefit has
      only been confirmed in transtibial amputees during decline and incline walking
      and increased walking speeds. REVIEWER'S CONCLUSIONS: There is insufficient
      evidence from high quality comparative studies for the overall superiority of any
      individual type of prosthetic ankle-foot mechanism. In high activity transfemoral
      amputees, there is limited evidence for the superiority of the Flex foot during
      level walking compared with the SACH foot in respect of energy cost and, gait
      efficiency. This benefit has only been confirmed in transtibial amputees during
      decline and incline walking and increased walking speeds. In prescribing
      prosthetic-ankle foot mechanisms for lower-limb amputees, practitioners should
      take into account availability, patient functional needs, and cost.

PMID- 14974051
TI  - Excitatory amino acid inhibitors for traumatic brain injury.
AB  - BACKGROUND: Glutamate is the principal excitatory neurotransmitter in the brain.
      Injury to the brain can cause an ionic imbalance in cerebral tissue, creating an
      excitotoxic cascade involving glutamate and other excitatory amino acids, that
      leads to neuronal death in the tissue surrounding the original injury site.
      Research has centred around inhibiting this increase in excitatory amino acid
      during injury either pre- or post-synaptically. Animal studies appeared
      promising, but as yet, those results have not been repeated in human clinical
      trials. OBJECTIVES: To assess systematically the efficacy of excitatory amino
      acid inhibitors on improving patient outcome following traumatic brain injury.
      SEARCH STRATEGY: Online searches of the databases; CENTRAL, MEDLINE, EMBASE,
      IDdb3, and Science Citation Index. Online searches of clinical trial registers.
      General online searches of the Internet. Authors of published works and
      associated pharmaceutical companies were contacted. SELECTION CRITERIA: Trials
      were included if they were randomised, double-blind, controlled trials where
      excitatory amino acid inhibitors were administered to patients with traumatic
      brain injury, within 24 hours of sustaining that injury, and compared to a
      control group. DATA COLLECTION AND ANALYSIS: Twelve trials, involving eight
      compounds, were identified that appeared to fit the inclusion criteria. Further
      investigation excluded three of these trials. Two of the remaining trials are
      ongoing. Of the seven included studies, one trial did not report GOS data and we
      were unable to acquire them. Three trials have not been published and the data
      were not made available to us. One trial is currently being prepared for
      publication, leaving two trials where data were available. Data were extracted by
      two independent reviewers. MAIN RESULTS: Data were available for two of the seven
      relevant trials identified, with 760 recruited participants. Mortality is similar
      between patients who receive excitatory amino acid inhibitors and those that
      receive placebo: odds ratio (OR) 1.11; 95% confidence interval (CI) 0.78, 1.60.
      Patients who have a favourable outcome six months after injury are also similar
      between treatment and placebo groups: OR 0.86; 95% CI 0.64, 1.16. REVIEWER'S
      CONCLUSIONS: The case for efficacy of excitatory amino acid inhibitor therapy
      remains unproven. To date, no product has proven to be efficacious (as determined
      by the criteria applied) for improving the outcomes of brain-injured patients.
      Early termination, unpublished, and underpowered studies limit a clear
      appreciation of the merits of this form of intervention. Additional studies, some
      of which remain in progress, may more clearly define the efficacy and
      effectiveness issues.

PMID- 14974052
TI  - Types of urethral catheters for management of short-term voiding problems in
      hospitalised adults.
AB  - BACKGROUND: Urinary tract infection is the most common hospital acquired
      infection. The major associated cause is indwelling urinary catheters. Currently
      there are many types of catheters available. A variety of specialised urethral
      catheters have been designed to reduce the risk of infection. These include
      antiseptic impregnated catheters and antibiotic impregnated catheters. Other
      issues that should be considered when choosing a catheter are ease of use,
      comfort and the cost. OBJECTIVES: The primary objective of this review was to
      determine the effect of type of indwelling urethral catheter on the risk of
      urinary tract infection in adults who undergo short-term urinary catheterisation.
      SEARCH STRATEGY: We searched the specialised trials registers of the Cochrane
      Incontinence Group (November 2003) and the Cochrane Renal Group (February 2003).
      We also examined the bibliographies of relevant articles and contacted catheter
      manufacturer representatives for trials. SELECTION CRITERIA: All randomised and
      quasi randomised trials comparing types of indwelling urinary catheters for short
      term catheterisation in hospitalised adults. Short-term catheterisation was
      defined as up to and including fourteen days, or other temporary short-term use
      as defined by the trialists. DATA COLLECTION AND ANALYSIS: Data were extracted by
      one reviewer and independently verified by a second reviewer. Disagreements were
      resolved by discussion. Data were processed as described in the Cochrane
      Handbook. Where data in trials were not fully reported, clarification was sought
      directly from the trialists (secondary sources were used to confirm results of
      one trial). MAIN RESULTS: Eighteen trials met the inclusion criteria involving
      4237 hospitalised adults in 17 parallel group trials and 27,878 adults in one
      large cluster-randomised cross-over trial. Only three of the possible six
      comparisons were addressed in these trials: antiseptic impregnated catheters
      versus standard catheters (n=11 trials), antibiotic impregnated catheters versus
      standard catheters (n=1 trial) and comparison of different standard catheters
      (n=6 trials). The results of the antiseptic versus standard catheter trials
      differed according to the antiseptic used to impregnate the catheter. The
      antiseptic catheters were either impregnated with silver oxide or silver alloy.
      Silver oxide catheters were not associated with a statistically significant
      reduction in bacteriuria in short-term catheterised hospitalised adults but the
      confidence intervals were wide (RR 0.89, 95% CI 0.68 to 1.15). Silver alloy
      catheters were found to significantly reduce the incidence of asymptomatic
      bacteriuria (RR 0.36, 95% CI 0.24 to 0.52) in hospitalised adults catheterised
      for less than one week. At greater than one week catheterisation the risk of
      asymptomatic bacteriuria was still reduced with the use of silver alloy catheters
      (RR 0.67, 95% CI 0.50 to 0.90). The risk of symptomatic urinary tract infection
      was also found to be reduced with the use of silver alloy catheters (RR 0.60, 95%
      CI 0.50 to 0.73). The randomised cross-over trial of silver alloy catheters
      versus standard catheters was excluded from the pooled results because data were
      not available prior to crossover. The results of this trial indicated benefit
      from the silver alloy catheters and included an economic analysis that indicated
      cost savings of between 3.3 per cent and 35.5 per cent. One small trial
      investigated men post radical prostatectomy catheterised with antibiotic
      impregnated catheter versus standard catheters and found a lower rate of
      asymptomatic bacteriuria in the antibiotic group at less than one week of
      catheterisation (RR 0.36, 95% CI 0.18 to 0.73). The trial at less than one week
      found that the risk of bacteriuria was also less in the antibiotic impregnated
      catheter group (RR 0.36, 95% CI 0.18 to 0.73); however, at greater than one week
      the result was not significant (RR 0.94, 95% CI 0.86 to 1.03). One of 56 men in
      the antibiotic impregnated group had a symptomatic UTI compared with 6 of 68 who
      had standard catheters (RR 0.20, 9h 6 of 68 who had standard catheters (RR 0.20,
      95% CI 0.03 to 1.63). Three trials compared two different types of standard
      catheters (defined as catheters that are not impregnated with antiseptics or
      antibiotics) to investigate infection but the results were not pooled because of
      the clinical and statistical heterogeneity between trials. Individual findings of
      the trials did not show whether or not one type of standard catheter reduced the
      risk of catheter related urinary tract infection compared to another type of
      standard catheter. Another three trials compared different types of standard
      catheters to investigate for adverse urethral effects in catheterised men. Once
      again the trials were not pooled due to significant heterogeneity; however, the
      results of the individual trials indicate a trend toward silicone catheters being
      less likely to result in adverse urethral effects in men. REVIEWER'S CONCLUSIONS:
      The results suggest that the use of silver alloy indwelling catheters for
      catheterising hospitalised adults short-term reduces the risk of catheter
      acquired urinary tract infection. Further economic evaluation is required to
      confirm that the reduction of infection compensates for the increased cost of
      silver alloy catheters.Catheters coated with a combination of minocycline and
      rifampin may also be beneficial in reducing bacteriuria in hospitalised men
      catheterised less than one week but this requires further testing. There was not
      enough evidence to suggest whether or not any standard catheter was better than
      another in terms of reducing the risk of urinary tract infection in hospitalised
      adults catheterised short-term. Siliconised catheters may be less likely to cause
      urethral side effects in men: however, this result should be interpreted with
      some caution as the trials were small and the outcome definitions and specific
      catheters compared varied.

PMID- 14974053
TI  - Effects of low sodium diet versus high sodium diet on blood pressure, renin,
      aldosterone, catecholamines, cholesterols, and triglyceride.
AB  - BACKGROUND: One of the controversies in preventive medicine is, whether a general
      reduction in sodium intake can decrease the blood pressure of a population and
      thereby reduce cardiovascular mortality and morbidity. In recent years the debate
      has been extended by studies indicating that reducing sodium intake has effects
      on the hormone and lipid profile. OBJECTIVES: To estimate the effects of low
      sodium versus high sodium intake on systolic and diastolic blood pressure (SBP
      and DBP), plasma or serum levels of renin, aldosterone, catecholamines,
      cholesterol and triglycerides. SEARCH STRATEGY: "MEDLINE" and reference lists of
      relevant articles were searched from 1966 through December 2001. SELECTION
      CRITERIA: Studies randomising persons to low sodium and high sodium diets were
      included if they evaluated at least one of the above outcome parameters. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted the data, which were
      analysed by means of Review Manager 4.1. MAIN RESULTS: In 57 trials of mainly
      Caucasians with normal blood pressure, low sodium intake reduced SBP by -1.27 mm
      Hg (CI: -1.76; -0.77)(p<0.0001) and DBP by -0.54 mm Hg (CI: -0.94; -0.14) (p =
      0.009) as compared to high sodium intake. In 58 trials of mainly Caucasians with
      elevated blood pressure, low sodium intake reduced SBP by -4.18 mm Hg (CI: -5.08;
      - 3.27) (p < 0.0001) and DBP by -1.98 mm Hg (CI: -2.46; -1.32) (p < 0.0001) as
      compared to high sodium intake. The median duration of the intervention was 8
      days in the normal blood pressure trials (range 4-1100) and 28 days in the
      elevated blood pressure trials (range 4-365). Multiple regression analyses showed
      no independent effect of duration on the effect size. In 8 trials of blacks with
      normal or elevated blood pressure, low sodium intake reduced SBP by -6.44 mm Hg
      (CI: -9.13; -3.74) (p < 0.0001) and DBP by -1.98 mm Hg (CI: -4.75; 0.78) (p =
      0.16) as compared to high sodium intake. The magnitude of blood pressure
      reduction was also greater in a single trial in Japanese patients. There was also
      a significant increase in plasma or serum renin, 304% (p < 0.0001), aldosterone,
      322%, (p < 0.0001), noradrenaline, 30% (p < 0.0001), cholesterol, 5.4% (p <
      0.0001) and LDL cholesterol, 4.6% (p < 0.004), and a borderline increase in
      adrenaline, 12% (p = 0.04) and triglyceride, 5.9% (p = 0.03) with low sodium
      intake as compared with high sodium intake. REVIEWER'S CONCLUSIONS: The magnitude
      of the effect in Caucasians with normal blood pressure does not warrant a general
      recommendation to reduce sodium intake. Reduced sodium intake in Caucasians with
      elevated blood pressure has a useful effect to reduce blood pressure in the short
      term. The results suggest that the effect of low versus high sodium intake on
      blood pressure was greater in Black and Asian patients than in Caucasians.
      However, the number of studies in black (8) and Asian patients (1) was
      insufficient for different recommendations. Additional long-term trials of the
      effect of reduced dietary sodium intake on blood pressure, metabolic variables,
      morbidity and mortality are required to establish whether this is a useful
      prophylactic or treatment strategy.

PMID- 14974054
TI  - Valproate for schizophrenia.
AB  - BACKGROUND: Many people with schizophrenia do not achieve a satisfactory
      treatment response with ordinary antipsychotic drug treatment. In these cases,
      various add-on medications are used, among them valproate. OBJECTIVES: To review
      the effects of valproate for the treatment of schizophrenia and schizophrenia
      like psychoses. SEARCH STRATEGY: The reviewers searched the Cochrane
      Schizophrenia Group's register (July 2002). This register is compiled of
      methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS,
      MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching
      of relevant journals and numerous conference proceedings. We also contacted a
      pharmaceutical company and authors of relevant studies in order to identify
      further trials. SELECTION CRITERIA: All randomised controlled trials comparing
      valproate to antipsychotics or to placebo (or no intervention), whether as the
      sole agent or as an adjunct to antipsychotic medication for the treatment of
      schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS:
      Citations and, where possible, abstracts were independently inspected by
      reviewers, papers ordered, re-inspected and quality assessed. Data were extracted
      independently by at least two reviewers. Dichotomous data were analysed using
      relative risks (RR) and the 95% confidence intervals (CI). Continuous data were
      analysed using weighted mean differences. Where possible the number needed to
      treat (NNT) or number needed to harm statistics were calculated. MAIN RESULTS:
      Five studies with a total of 379 participants were included. All trials examined
      the effectiveness of valproate as an adjunct to antipsychotics. With one
      exception the studies were small, short-term and incompletely reported. Adding
      valproate was as acceptable as adding placebo to antipsychotic drugs (n=130, RR
      leaving the study early 1.6 CI 0.8 to 3.1). No significant effect of using
      valproate as an adjunct to antipsychotic medication on the participants' global
      state or general mental state at the endpoint studies was evident. However, one
      study showed a quicker onset of action in the combination group. Participants
      receiving valproate more frequently experienced sedation than those in the
      placebo group. The effects of valproate on important subgroups such as those with
      schizophrenia and aggressive behaviour or those with schizoaffective disorder are
      unknown. REVIEWER'S CONCLUSIONS: Based on randomised trial-derived evidence which
      is currently available, there are no data to support or to refute the use of
      valproate as a sole agent for schizophrenia. There is some evidence for a more
      rapid improvement with valproate augmentation, but this effect vanished over
      time. Given this limited evidence, further large, simple well-designed and
      reported trials are necessary. These might focus on people with schizophrenia and
      violent episodes, on those with treatment resistant forms of the disorder and on
      people with schizoaffective disorders.

PMID- 14974055
TI  - Thiamine for Wernicke-Korsakoff Syndrome in people at risk from alcohol abuse.
AB  - BACKGROUND: Autopsy studies suggest that Wernicke-Korsakoff Syndrome (WKS) is not
      a rare disorder, particularly in individuals who abuse alcohol. Thiamine has been
      established as the treatment of choice for over 50 years, but there is
      uncertainty about appropriate dosage and duration. Current practice guidelines
      are based on case reports and clinical experience. OBJECTIVES: To determine the
      quality of evidence for the efficacy of thiamine in preventing and treating the
      manifestations of WKS as a consequence of alcohol excess, and if so in which form
      it should be given, at what dose and for how long. SEARCH STRATEGY: Trials were
      identified from the latest updated search of the Specialized Register of the
      Cochrane Dementia and Cognitive Improvement Group on 3 February 2003 using the
      terms "(thiamin* or aneurin*) and (Korsakoff* or Wernicke* or alcohol*). The
      CDCIG Specialized register contains up-to-date records from all major health care
      databases (Medline, Embase, PsycInfo, Cinahl and others) as well as from many
      trials databases. SELECTION CRITERIA: All randomized trials in which treatment
      with thiamine or thiamine-containing products was administered and compared with
      alternative interventions for people with, or at risk of developing, WKS
      secondary to alcohol abuse. DATA COLLECTION AND ANALYSIS: All abstracts were
      independently inspected by two reviewers (ED & PB) and relevant papers were
      retrieved and assessed for methodological quality using Cochrane Reviewers'
      Handbook criteria. MAIN RESULTS: Two studies were identified that met the
      inclusion criteria, but only one contained sufficient data for quantitative
      analysis. Ambrose (2001) randomized participants (n=107) to one of five doses of
      intramuscular thiamine and measured outcomes after 2 days of treatment. We
      compared the lowest dose (5mg/day) with each of the other four doses. There was a
      significant difference in favour of the 200mg/day compared with the 5 mg/day dose
      in the number of trials taken to reach criterion on a delayed alternation test
      (MD -17.90, 95% CI -35.4 to -0.40, p=0.04). No significant differences emerged in
      comparing the other doses with 5 mg/day. The pattern of results did not present a
      simple dose-response relationship. The study had methodological shortcomings in
      design and the presentation of results that limited further analysis. REVIEWER'S
      CONCLUSIONS: There is insufficient evidence from randomized controlled clinical
      trials to guide clinicians in the dose, frequency, route or duration of thiamine
      treatment for prophylaxis against or treatment of WKS due to alcohol abuse.

PMID- 14974056
TI  - High-frequency ventilation versus conventional ventilation for treatment of acute
      lung injury and acute respiratory distress syndrome.
AB  - BACKGROUND: High-frequency ventilation is often used to treat patients with acute
      lung injury (ALI) or acute respiratory distress syndrome (ARDS) but the effect of
      this treatment on clinical outcomes has not been well established. OBJECTIVES:
      The objective of this review is to examine the effect of high-frequency
      ventilation compared with conventional ventilation as a therapy for ALI or ARDS
      in children (1 to 17 years old) and adults in order to quantify its effect on
      patient outcome (mortality, morbidity and other relevant outcomes). SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library, issue 4, 2002), MEDLINE (1966 to October Week 5,
      2002), EMBASE (1980 to Week 51, 2002), World Wide Web (www.controlled-trials.com,
      ARDS clinical network), and used Cited Reference Search (Web of Science 1988 to
      2002, for specific reference lists of articles). We also contacted authors from
      each included trial, as well as manufacturers of high-frequency ventilators and
      other researchers in the field. SELECTION CRITERIA: Randomized controlled
      clinical trials of children and adults comparing treatment using high-frequency
      ventilation with conventional ventilation for patients diagnosed with ALI or
      ARDS. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial
      quality and extracted data. Study authors were contacted for additional
      information. MAIN RESULTS: Two trials met the inclusion criteria for this review.
      One trial recruited children (including some children less than one year old) (n
      = 58) and the other recruited adults (n = 148). Both trials used a high-frequency
      oscillatory ventilator as the intervention and included variable use of lung
      volume recruitment strategies. The intervention groups showed a trend towards
      lower 30 day mortality (children relative risk (RR) 0.83, 95% confidence interval
      (CI) 0.43 to 1.62; adults RR 0.72, 95% CI 0.50 to 1.03), although neither study
      showed a statistically significant difference. Similarly, there was no
      statistically significant difference between the intervention and control groups
      for 'Total length of ventilator days' (WMD) -2.00, 95% CI -18.36 to 14.36; and
      WMD 2.00, 95% CI -6.55 to 10.55 for the child and adult trials respectively). The
      studies used only proxies to measure long-term quality of life. There was a
      statistically significant reduction in the risk of requiring supplemental oxygen
      amongst survivors at 30 days in the paediatric study (RR 0.36, 95% CI 0.14 to
      0.93). REVIEWER'S CONCLUSIONS: There is not enough evidence to conclude whether
      high-frequency ventilation reduces mortality or long-term morbidity in patients
      with ALI or ARDS; further trials are needed.

PMID- 14974057
TI  - Non-invasive positive pressure ventilation for treatment of respiratory failure
      due to exacerbations of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Non-invasive positive pressure ventilation (NPPV) is being used
      increasingly in the management of patients admitted to hospital with acute
      respiratory failure secondary to an exacerbation of chronic obstructive pulmonary
      disease (COPD). OBJECTIVES: To determine the efficacy of NPPV in the management
      of patients with respiratory failure due to an acute exacerbation of COPD. SEARCH
      STRATEGY: An initial search was performed using the Cochrane Airways Group trials
      register and other relevant electronic databases. An updated search was conducted
      in September 2003. SELECTION CRITERIA: Randomised controlled trials comparing
      NPPV plus usual medical care (UMC) versus UMC alone were selected. Trials needed
      to recruit adult patients admitted to hospital with respiratory failure due to an
      exacerbation of COPD and with PaCO(2) > 6 kPa (45 mmHg). DATA COLLECTION AND
      ANALYSIS: Two reviewers independently selected articles for inclusion, evaluated
      methodological quality of the studies and abstracted the data. MAIN RESULTS:
      Fourteen studies were included in the review. NPPV resulted in decreased
      mortality (Relative Risk 0.52; 95%CI 0.35, 0.76), decreased need for intubation
      (RR 0.41; 95%CI 0.33, 0.53), reduction in treatment failure (RR 0.48; 95%CI 0.37,
      0.63), rapid improvement within the first hour in pH (Weight Mean Difference
      0.03; 95%CI 0.02, 0.04), PaCO(2) (WMD -0.40 kPa; 95%CI -0.78, -0.03) and
      respiratory rate (WMD -3.08 bpm; 95%CI -4.26, -1.89). In addition, complications
      associated with treatment (RR 0.38; 95%CI 0.24, 0.60) and length of hospital stay
      (WMD -3.24 days; 95%CI -4.42, -2.06) was also reduced in the NPPV group.
      REVIEWER'S CONCLUSIONS: Data from good quality randomised controlled trials show
      benefit of NPPV as first line intervention as an adjunct therapy to usual medical
      care in all suitable patients for the management of respiratory failure secondary
      to an acute exacerbation of COPD. NPPV should be considered early in the course
      of respiratory failure and before severe acidosis ensues, as a means of reducing
      the likelihood of endotracheal intubation, treatment failure and mortality.

PMID- 14974058
TI  - Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal
      colic.
AB  - BACKGROUND: Renal colic is a common cause of acute severe pain. Both opioids and
      nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for treatment, but
      the relative efficacy of these drugs is uncertain. OBJECTIVES: To examine the
      benefits and disadvantages of NSAIDs and opioids for the management of pain in
      acute renal colic. SEARCH STRATEGY: We searched the Cochrane Renal Group's
      specialised register (May 2003), the Cochrane Central Register of Randomised
      Controlled Trials (CENTRAL - The Cochrane Library issue 2, 2003), MEDLINE (1966 -
      31 January 2003), EMBASE (1980 - 31 January 2003) and handsearched reference
      lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) comparing any opioid with any NSAID, regardless of dose or route of
      administration were included. DATA COLLECTION AND ANALYSIS: Data was extracted
      and quality assessed independently by two reviewers, with differences resolved by
      discussion. Dichotomous outcomes are reported as relative risk (RR) and
      measurements on continuous scales are reported as weighted mean differences (WMD)
      with 95% confidence intervals. Subgroup analysis by study quality, drug type and
      drug route have been performed where possible to explore reasons for
      heterogeneity. MAIN RESULTS: Twenty trials from nine countries with a total of
      1613 participants were identified. Both NSAIDs and opioids lead to clinically
      significant falls in patient-reported pain scores. Due to unexplained
      heterogeneity these results could not be pooled although 10/13 studies reported
      lower pain scores in patients receiving NSAIDs. Patients treated with NSAIDs were
      significantly less likely to require rescue medication (RR 0.75, 95% CI 0.61 to
      0.93, P = 0.007), though most of these trials used pethidine. The majority of
      trials showed a higher incidence of adverse events in patients treated with
      opioids, but there was significant heterogeneity between studies so the results
      could not be pooled. There was significantly less vomiting in patients treated
      with NSAIDs (RR 0.35, 95% CI 0.23 to 0.53, P < 0.00001). In particular, patients
      receiving pethidine had a much higher rate of vomiting compared with patients
      receiving NSAIDs. Gastrointestinal bleeding and renal impairment were not
      reported. REVIEWER'S CONCLUSIONS: Both NSAIDs and opioids can provide effective
      analgesia in acute renal colic. Opioids are associated with a higher incidence of
      adverse events, particularly vomiting. Given the high rate of vomiting associated
      with the use of opioids, particularly pethidine, and the greater likelihood of
      requiring further analgesia, we recommend that if an opioid is to be used it
      should not be pethidine.

PMID- 14974059
TI  - Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease.
AB  - BACKGROUND: Spasticity commonly affects patients with motor neuron disease and it
      is likely to contribute to worsening muscle dysfunction, increased difficulty
      with activities of daily living and deteriorating quality of life. OBJECTIVES:
      The objective of this review is to systematically review all types of treatments
      for spasticity in amyotrophic lateral sclerosis, also known as motor neuron
      disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group
      specialised trials register (searched January 2003), MEDLINE (January 1966 to
      January 2003), EMBASE (January 1980 to January 2003), CINAHL (January 1982 to
      January 2003), AMED (January 1985 to January 2003) and LILACS (January 1982 to
      January 2003) for randomized controlled trials. We reviewed the bibliographies of
      the randomized trials identified, and contacted trial authors and known experts
      in the field. SELECTION CRITERIA: We included quasi-randomized or randomized
      controlled trials of participants with probable or definite amyotrophic lateral
      sclerosis according to the El Escorial diagnostic criteria (or a revised version)
      or the Airlie House revision. We would have included trials of physical therapy,
      modalities, prescription medications, non-prescription medications, chemical
      neurolysis, surgical interventions, alternative therapies. Our primary outcome
      measure was reduction in spasticity at three months or greater as measured by
      Ashworth (or modified Ashworth) spasticity scale. Our secondary outcome measures
      were: validated measures based on history, physical examination, physiological
      measures, measures of function, measures of quality of life, serious adverse
      events, and measures of cost. DATA COLLECTION AND ANALYSIS: We identified only
      one randomized controlled trial that met the inclusion criteria for this review.
      Two authors extracted the data. We also contacted the author of the paper and
      obtained further information not available in the published article. MAIN
      RESULTS: The included study was a trial of moderate intensity, endurance type
      exercise versus 'usual activities' in 25 patients with amyotrophic lateral
      sclerosis. At three months patients performing the 15 minute twice daily
      exercises had significantly less spasticity (mean reduction of 0.43 Ashworth
      grades versus an increase of 0.25 in controls), as measured by the Ashworth
      scale. REVIEWER'S CONCLUSIONS: Individualized, moderate intensity, endurance type
      exercises for the trunk and limbs may help to reduce spasticity in motor neuron
      disease. No other medical, surgical or alternative treatment and therapy has been
      evaluated in a randomized fashion in this patient population.

PMID- 14974060
TI  - Non-pharmaceutical measures for prevention of post-thrombotic syndrome.
AB  - BACKGROUND: Post-thrombotic syndrome (PTS) is a long-term complication of deep
      vein thrombosis (DVT) characterised by chronic pain, swelling and skin changes in
      the affected limb. One in every three patients with DVT will develop post
      thrombotic complications within five years. OBJECTIVES: To determine the relative
      effectiveness of, and the rate of complications using non-pharmaceutical
      interventions in patients with DVT in the prevention of PTS. SEARCH STRATEGY: The
      reviewers searched the Cochrane Peripheral Vascular Diseases Group Specialised
      Trials Register (last searched January 2003), and the Cochrane Central Register
      of Controlled Trials (CENTRAL) (last searched Issue 4, 2002). In addition, hand
      searching of non-listed journals and personal communications with researchers was
      undertaken. SELECTION CRITERIA: Randomised controlled trials (RCTs) of non
      pharmaceutical interventions, such as bandaging and elastic stockings in patients
      with clinically confirmed DVT. The primary outcome was the occurrence of PTS.
      There was no restriction on date or language. One reviewer (DNK) identified and
      assessed titles and abstracts for relevance. This was verified independently by a
      second reviewer (RS). DATA COLLECTION AND ANALYSIS: Data extraction was
      undertaken independently by two reviewers (DNK, RS), using data extraction
      sheets. MAIN RESULTS: Three RCTs that evaluated compression therapy were
      identified. Two studies compared elastic compression stockings with a pressure of
      30-40 mm Hg at the ankle with no intervention applied directly after an episode
      of DVT. The other small study compared elastic compression stockings (pressure 20
      30 mm Hg) with stockings that were one to two sizes too large in patients one
      year after DVT. Overall, in the treatment group at two years, the use of elastic
      compression stockings was associated with a highly statistically significant
      reduction in the incidence of PTS with odds ratio (OR) 0.31 (95% confidence
      interval (CI) 0.20 to 0.48). In addition, the incidence of severe PTS was reduced
      from OR 0.39 (95% CI 0.20 to 0.76). In another RCT that considered the first nine
      days post DVT, no difference in the incidence of pulmonary embolism and size of
      thrombus in the femoral vein was found. A statistically significant reduction (p
      <0.05) was found in pain, swelling and clinical scores, favouring the compression
      group. REVIEWER'S CONCLUSIONS: There is substantial evidence that elastic
      compression stockings reduce the occurrence of PTS after DVT. No serious adverse
      effects were mentioned in the studies. Hence, elastic compression stockings
      should be added to the treatment of DVT to prevent the development of post
      thrombotic syndrome.

PMID- 14974061
TI  - Day care versus in-patient surgery for age-related cataract.
AB  - BACKGROUND: Age-related cataract accounts for more than 40% of cases of blindness
      in the world with the majority of people who are blind from cataract found in the
      developing world. With the increased number of people with cataract there is an
      urgent need for cataract surgery to be made available as a day-care procedure.
      OBJECTIVES: The objective of this review is to provide reliable evidence
      regarding the safety, feasibility, effectiveness and cost-effectiveness of
      cataract extraction performed as day-care versus in-patient procedure. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (which contains the Cochrane Eyes and Vision Group trials register) on
      The Cochrane Library (Issue 4 2002), MEDLINE (1966 to November 2002), EMBASE
      (1980 to November 2002) and LILACS (November 2002). SELECTION CRITERIA: This
      review includes randomised controlled trials comparing day-care and in-patient
      surgery for age-related cataract. The primary outcome was the achievement of a
      satisfactory visual acuity six weeks after the operation. DATA COLLECTION AND
      ANALYSIS: Although two trials are included in the review, adequate data were
      available for only one trial and therefore pooling of data from studies was not
      attempted. A descriptive summary is presented. MAIN RESULTS: Two trials,
      involving a total of 1284 people, are included in this review. One trial reported
      statistically significant differences in early postoperative complication rates
      in the day-care group, with an increased risk of increased intraocular pressure,
      which had no clinical relevance to visual outcomes four months postoperatively.
      The mean change in visual acuity (Snellen lines) of the operated eye four months
      postoperatively was 4.1 (standard deviation (SD) 2.3) for the day-care group and
      4.1 (SD 2.2) for the in-patient group and not statistically significant. The four
      month postoperative mean change in quality of life score measured using the VF14
      showed minimal differences between the two groups. Costs were 20% more for the in
      patient group and this was attributed to higher costs for overnight stay. One
      study only reported hotel costs for the non-hospitalised participants making
      aggregation of data on costs impossible. REVIEWER'S CONCLUSIONS: This review
      provides some evidence that there is a cost saving but no significant difference
      in outcome or risk of postoperative complications between day-care and in-patient
      cataract surgery. This is based on one detailed and methodologically sound trial
      conducted in the developed world. The success, safety and cost-effectiveness of
      cataract surgery as a day-care procedure appears to be acceptable but additional
      well-designed trials are required to confirm these perceptions.

PMID- 14974062
TI  - Alpha lipoic acid for dementia.
AB  - BACKGROUND: Oxidative processes have been implicated in the pathogenesis of
      neurodegenerative dementias including Alzheimer's disease. Protecting the central
      nervous system against these damaging mechanisms may be a useful therapeutic
      approach. Alpha lipoic acid (ALA) is an endogenous antioxidant that interrupts
      cellular oxidative processes in both its oxidized and reduced forms. These
      properties might qualify ALA for a modulatory role in the treatment of people
      with dementia. OBJECTIVES: To assess the role and clinical efficacy of alpha
      lipoic acid in the treatment of dementia. SEARCH STRATEGY: A search of the
      Specialized Register of the Cochrane Dementia and Cognitive Improvement Group
      (CDCIG) on 3 February 2003 using the terms 'alpha lipoic acid' and 'thioctic'.
      The CDCIG Specialized register is updated regularly and contains records from all
      major health care databases (MEDLINE, EMBASE, PsycInfo, CINAHL) as well as from
      many trials databases. SELECTION CRITERIA: All double-blind randomized placebo
      controlled trials examining the efficacy of alpha lipoic acid in dementia DATA
      COLLECTION AND ANALYSIS: No trials were found that met the selection criteria
      MAIN RESULTS: No meta-analysis could be performed. A systematic search of the
      Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, as
      well as registers of ongoing and unpublished trials could not identify any
      studies investigating the use of ALA for dementia. REVIEWER'S CONCLUSIONS: In the
      absence of randomized double-blind placebo-controlled trials investigating ALA
      for dementia, no evidence exists to explore any potential effects. Until data
      from trials become available for analysis, ALA cannot be recommended for people
      with dementia.

PMID- 14974063
TI  - Manipulation and mobilisation for mechanical neck disorders.
AB  - BACKGROUND: Neck disorders are common, disabling, and costly. The effectiveness
      of manipulation and mobilisation remains unclear. OBJECTIVES: To assess whether
      manipulation and mobilisation, either alone or in combination with other
      treatments, relieve pain or improve function/disability, patient satisfaction,
      and global perceived effect in adults with mechanical neck disorders (MND).
      SEARCH STRATEGY: Computerised bibliographic databases including CENTRAL, MEDLINE,
      EMBASE, MANTIS, CINAHL, and ICL, were searched without language restrictions from
      their respective starting dates to March 2002. SELECTION CRITERIA: The studies
      had to be randomised (RCT) or quasi-randomised and investigate the use of
      manipulation or mobilisation as a treatment for mechanical neck disorders. DATA
      COLLECTION AND ANALYSIS: Two independent reviewers conducted citation
      identification, study selection, data abstraction, and methodological quality
      assessment. Using a random effects model, relative risk and standardised mean
      differences were calculated. The reasonableness of combining studies was assessed
      on clinical and statistical grounds. In the absence of heterogeneity, pooled
      effect measures were calculated. MAIN RESULTS: Of the 33 selected trials, 42%
      were high quality trials. Single sessions of manipulation or multiple sessions (3
      to 11 weeks) of manipulation or mobilisation, or manipulation and mobilisation
      showed a nonsignificant benefit in pain relief when assessed against placebo,
      control groups or other treatments for acute/subacute/chronic MNDs with or
      without headache. There was strong evidence of benefit favouring multimodal care
      over a waiting list control for pain reduction [pooled SMD -0.85 (95% CI: -1.20
      to -0.50)], improvement in function [pooled SMD -0.57 (95% CI: -0.94 to -0.21)]
      and global perceived effect [SMD -2.73 (95% CI: -3.30 to -2.16)] for
      subacute/chronic MND with or without headache. The common elements in this care
      strategy were mobilisation and/or manipulation plus exercise. There was moderate
      evidence of no difference in effect when multimodal care was compared to various
      other treatments. REVIEWER'S CONCLUSIONS: Multimodal care has short-term and long
      term maintained benefits for subacute/chronic MND with or without headache. The
      common elements in this care strategy were mobilisation and/or manipulation plus
      exercise. The evidence did not favour manipulation and/or mobilisation done alone
      or in combination with various other physical medicine agents; when compared to
      one another, neither was superior. There was insufficient evidence available to
      draw conclusions for neck disorder with radicular findings. The added benefit of
      exercise needs to be further explored. Factorial design would help determine the
      active treatment agent(s) within a treatment mix. Phase II trials would help
      identify the most effective treatment characteristics and dosages. Greater
      attention to methodological quality is needed.

PMID- 14974064
TI  - Surgical versus non-surgical treatment for acute anterior shoulder dislocation.
AB  - BACKGROUND: Acute anterior shoulder dislocation is the commonest type of shoulder
      dislocation. Subsequently, the shoulder is less stable and more susceptible to re
      dislocation, especially in active young adults. OBJECTIVES: We aimed to compare
      surgical versus non-surgical treatment for acute anterior dislocation of the
      shoulder. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries
      Group specialised register (August 2003), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library Issue 3, 2003), MEDLINE (1966 to
      September week 3 2003), EMBASE (1988 to 2003 week 39), the National Research
      Register (UK) (Issue 3, 2003), conference proceedings and reference lists of
      articles. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials
      comparing surgical with conservative interventions for treating acute anterior
      shoulder dislocation. DATA COLLECTION AND ANALYSIS: Selection of the included
      trials was by all three reviewers. Two reviewers independently assessed
      methodological quality and extracted data. Where appropriate, results of
      comparable studies were pooled. MAIN RESULTS: Five studies were included. These
      involved a total of 239 young (mainly aged around 22 years) active and mainly
      male people, all of whom had had a primary (first time) traumatic anterior
      shoulder dislocation. Methodological quality was variable, but notably there was
      insufficient information to judge whether allocation was effectively concealed in
      all five trials. Two trials, involving 115 participants, were only reported in
      conference abstracts.One trial involving military personnel reported that all had
      returned to active duty. Another trial reported similar numbers in the two
      intervention groups with reduced sports participation, and a third trial reported
      that significantly fewer people in the surgical group failed to attain previous
      levels of sports activity. Pooled results from all five trials showed that
      subsequent instability, either redislocation or subluxation, was statistically
      significantly less frequent in the surgical group (relative risk (RR) 0.20;
      95%confidence interval (CI) 0.11 to 0.33). This result remained statistically
      significant (RR 0.32, 95%CI 0.17 to 0.59) for the three trials reported in full.
      Half (17/33) of the conservatively treated patients with shoulder instability in
      these three trials opted for subsequent surgery.Different, mainly patient-rated,
      functional assessment measures for the shoulder were recorded in the five trials.
      The results were more favourable, usually statistically significantly so, in the
      surgically treated group. Aside from a septic joint in a surgically treated
      patient, there were no other treatment complications reported. There was no
      information on shoulder pain, long-term complications such as osteoarthritis or
      on service utilisation and resource use. REVIEWER'S CONCLUSIONS: The limited
      evidence available supports primary surgery for young adults, usually male,
      engaged in highly demanding physical activities who have sustained their first
      acute traumatic shoulder dislocation. There is no evidence available to determine
      whether non-surgical treatment should not remain the prime treatment option for
      other categories of patient. Sufficiently powered, good quality and adequately
      reported randomised trials of good standard surgical treatment versus good
      standard conservative treatment for well-defined injuries are required; in
      particular, for patient categories at lower risk of activity-limiting recurrence.
      Long term surveillance of outcome, looking at shoulder disorders including
      osteoarthritis is also required. Reviews comparing different surgical
      interventions and different conservative interventions including rehabilitation
      are needed.

PMID- 14974065
TI  - Prophylactic antibiotics to reduce morbidity and mortality in ventilated newborn
      infants.
AB  - BACKGROUND: Bacterial colonisation of the respiratory tract is associated with
      intubation and may increase the risk of acquiring infection. This may prolong the
      need for mechanical ventilation and increase the risk of chronic lung disease.
      The use of prophylactic antibiotics has been advocated for all mechanically
      ventilated newborns in order to reduce the risk of colonisation and acquired
      infection. Countering this is the possibility that harm may outweigh benefit.
      OBJECTIVES: To assess the effects of prophylactic antibiotics in reducing
      mortality and morbidity in intubated and ventilated newborn infants who are not
      known to have infection. In separate comparisons, we reviewed two different
      policies regarding the prophylactic use of antibiotics in intubated, ventilated
      infants: 1) among babies who are being intubated for mechanical ventilation, a
      policy of prophylactic antibiotics for the duration of intubation versus placebo
      or no treatment. 2) among intubated, ventilated babies who had been started on
      antibiotics at the time of intubation but whose initial cultures to rule our
      sepsis are negative, a policy of continuing versus discontinuing prophylactic
      antibiotics. SEARCH STRATEGY: We searched MEDLINE (January 1966 to May 2003),
      CINAHL (1982 to May 2003), the Cochrane Central Register of Controlled Trials
      (The Cochrane Library, Issue 1, 2003), the Cochrane Neonatal Group Specialised
      Register and reference lists of articles. SELECTION CRITERIA: Randomised
      controlled trials of sufficient quality in which mechanically ventilated newborn
      infants are randomised to receive prophylactic antibiotics versus placebo or no
      treatment. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      trial quality. MAIN RESULTS: One study, of insufficient quality, met the criteria
      for inclusion in this review. REVIEWER'S CONCLUSIONS: There is no evidence from
      randomised trials to support or refute the use of prophylactic antibiotics when
      commencing mechanical ventilation in newborn infants, or to support or refute
      continuing antibiotics once initial cultures rule out infection in mechanically
      ventilated newborn infants.

PMID- 14974066
TI  - Direct versus indirect veneer restorations for intrinsic dental stains.
AB  - BACKGROUND: Patients with discoloured teeth frequently present to the dentist
      requesting restorations designed to improve their appearance. For teeth that are
      sound, this might include the use of a veneer restoration. The veneer acts as a
      thin layer of a material covering the labial surface of a tooth and can be
      applied directly to the tooth, or by using indirect methods. OBJECTIVES: To
      examine the effectiveness of direct versus indirect laminate veneer restorations.
      SEARCH STRATEGY: The following electronic databases were searched: The Cochrane
      Oral Health Group's Trials Register, The Cochrane Central Register of Controlled
      Trials (CENTRAL), (The Cochrane Library Issue 3, 2002), MEDLINE (1980 to
      19/11/2002) and EMBASE (1980 to 19/11/2002). There was no restriction on
      language. SELECTION CRITERIA: All randomised controlled trials (RCTs) of
      participants with permanent anterior teeth suitable for restorations using
      laminate veneers, comparing direct (different composite materials) and indirect
      techniques for making dental veneers. The indirect restorations may be either
      composite or porcelain. The primary outcome was restoration failure. DATA
      COLLECTION AND ANALYSIS: Assessment of relevance and validity and data extraction
      were conducted in triplicate. Authors of the primary studies were contacted to
      provide additional information as necessary. MAIN RESULTS: Six full publications
      were screened as being potentially relevant to the review, only one trial was
      found to meet the review's inclusion criteria. Although the trial met the
      review's inclusion criteria with regard to participant characteristics,
      interventions and outcomes assessed, problems with the reporting of the data
      prevented any statistical analysis of the results. REVIEWER'S CONCLUSIONS: There
      is no reliable evidence to show a benefit of one type of veneer restoration
      (direct or indirect) over the other with regard to the longevity of the
      restoration.

PMID- 14974067
TI  - Inhaled anti-cholinergics for prolonged non-specific cough in children.
AB  - BACKGROUND: Non-specific cough is defined as non-productive cough in the absence
      of identifiable respiratory disease or known aetiology. It is commonly seen in
      paediatric practice. These children are treated with a variety of therapies
      including inhaled anti-cholinergic medications. OBJECTIVES: To determine the
      efficacy of inhaled anti-cholinergic medications in the management of prolonged
      non-specific cough in children. SEARCH STRATEGY: The Cochrane Register of
      Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register and
      Cochrane Airways Group, MEDLINE and EMBASE databases were searched. Relevant
      pharmaceutical companies were contacted. The latest searches were performed in
      July 2003. SELECTION CRITERIA: All randomised controlled trials comparing inhaled
      anti-cholinergic medication with a placebo medication. DATA COLLECTION AND
      ANALYSIS: Results of searches were reviewed against pre-determined criteria for
      inclusion. No eligible trials were identified and thus no data were available for
      analysis. A single small trial in adults has been reported. MAIN RESULTS: No
      randomised-controlled trials that examined the efficacy of inhaled anti
      cholinergic medications in the management of prolonged non-specific cough in
      children were found. REVIEWER'S CONCLUSIONS: There is currently no evidence to
      support the use of inhaled anti-cholinergics for symptomatic control of non
      specific cough in children. Further research examining the effects of this
      intervention is needed.

PMID- 14974068
TI  - Donepezil for vascular cognitive impairment.
AB  - BACKGROUND: Vascular disease is the second commonest cause of dementia after
      Alzheimer's disease. There are difficulties in classifying patients with this
      type of cognitive impairment owing to varied clinical presentation and different
      types of arterial disease. There is some degree of overlap in the neuropathology
      of Alzheimer's and vascular dementia. Deficient cholinergic neurotransmission, a
      characteristic of Alzheimer's disease, has been postulated to contribute to the
      cognitive impairment of vascular disease of the brain. Cholinesterase inhibitors,
      such as donepezil, may therefore be a rational treatment. OBJECTIVES: To assess
      the clinical efficacy and tolerability of donepezil on cognitive function,
      clinical global impression, activities of daily living and social functioning of
      people with vascular cognitive impairment. SEARCH STRATEGY: Relevant randomized
      controlled trials were identified from a search of the Cochrane Dementia and
      Cognitive Improvement Group Specialized Register on 21 July 2003 using the terms
      donepezil, E2020 and Aricept. This Register consists of records from all major
      healthcare databases and many ongoing trials databases. Unpublished trials were
      requested from the drug company Eisai Inc and they provided us with the required
      data. SELECTION CRITERIA: All unconfounded randomized double-blind trials
      comparing donepezil with placebo were eligible for inclusion. Trials using
      combinations of donepezil with other pharmacological interventions were excluded.
      DATA COLLECTION AND ANALYSIS: Both reviewers assessed studies against the
      criteria for inclusion and extracted data. Data were pooled where appropriate,
      and weighted mean differences or Peto odds ratios with 95% confidence intervals
      calculated. Intention-to-treat analysis was undertaken when possible. MAIN
      RESULTS: Two large-scale, randomized, double-blind, parallel-group controlled
      trials were identified for inclusion. A total of 1219 people with mild to
      moderate cognitive decline due to probable or possible vascular dementia
      (according to the NINCDS/AIREN criteria and the Hachinski Ischemia Scale) were
      recruited. Donepezil, at doses of 5 or 10 mg a day was compared with placebo for
      24 weeks. For each outcome measure, mean change from baseline at weeks 12 and 24,
      using a last observation carried forward analysis, was calculated. Cognitive
      function: The donepezil groups showed statistically significantly better
      performance than the placebo groups on the cognitive subscale of the Alzheimer's
      Disease Assessment Scale (ADAS-Cog) at 12 and 24 weeks. The donepezil groups
      produced statistically significantly better scores than the placebo groups on the
      Mini-Mental State Examination (MMSE) at 12 and 24 weeks. Global function: The sum
      of the boxes of the Clinical Dementia Rating (CDR-SB) showed at 24 weeks a
      statistically significant benefit of 10 mg donepezil daily over both placebo and
      a 5 mg daily dosage. The Clinician's Interview-Based Impression of Change-plus
      version (CIBIC-plus) showed improved global function of participants taking 5 mg
      of donepezil daily compared with the placebo group but this was not seen in the
      higher dose group. Activities of daily living and social behaviour: On the
      Instrumental Activity of Daily Living (IADL) scale, there was no statistically
      significant difference between the groups taking donepezil 5mg per day donepezil
      and placebo, but the group taking 10 mg of donepezil a day showed benefit
      compared with placebo There were statistically significant benefit for donepezil
      at either dosage compared with placebo on the Alzheimer's Disease Functional
      Assessment and Change Scale (ADFACS). Tolerability and adverse effects: Broad
      range of adverse events were reported in the studies and data confirmed that
      donepezil was well tolerated, and most of the side effects were transient and
      were resolved by stopping the medication. Some of these events, especially
      nausea, diarrhoea, anorexia and cramp appeared more frequently on the 10 mg dose
      where there was a statistically significant difference compared with placebo.
      Drop-out: The drop-out rate was similar between the groups, 84.2% (330) patients
      completed the studies. The withdrawal rate was low and due mainly to side
      effects. REVIEWER'S CONCLUSIONS: Evidence from the available studies support the
      benefit of donepezil in improving cognition function, clinical global impression
      and activities of daily living in patients with probable or possible mild to
      moderate vascular cognitive impairment after 6 months treatment. Extending
      studies for longer periods would be desirable to establish the efficacy of
      donepezil in patients with advanced stages of cognitive impairment. Moreover,
      there is an urgent need for establishing specific clinical diagnostic criteria
      and rating scales for vascular cognitive impairment.

PMID- 14974069
TI  - Interventions for recurrent idiopathic epistaxis (nosebleeds) in children.
AB  - BACKGROUND: Recurrent idiopathic epistaxis (nosebleeds) in children is repeated
      nasal bleeding in patients up to the age of 16 for which no specific cause has
      been identified. Although nosebleeds are very common in children, and most cases
      are self-limiting or settle with simple measures (such as pinching the nose),
      more severe recurrent cases can require treatment from a healthcare professional.
      However, there is no consensus on the effectiveness of the different clinical
      interventions currently used in managing this condition. OBJECTIVES: To assess
      the effects of different interventions for the management of recurrent idiopathic
      epistaxis in children. SEARCH STRATEGY: We searched the Cochrane ENT Group
      Specialised Register, the Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library Issue 3, 2003), MEDLINE (January 1966 to August
      2003), EMBASE (January 1980 to August 2003), CINAHL (January 1982 to August
      2003), and reference lists of relevant articles. SELECTION CRITERIA: We
      identified all randomised controlled trials (with or without blinding) in which
      any surgical or medical intervention for the treatment of recurrent idiopathic
      epistaxis in children was evaluated in comparison with either no treatment, a
      placebo, or another intervention, and in which the frequency and severity of
      episodes of nasal bleeding following treatment was stated or calculable. The full
      text articles of all the retrieved trials of possible relevance were reviewed by
      the two reviewers and the inclusion criteria applied independently. DATA
      COLLECTION AND ANALYSIS: Trials were graded for methodological quality using the
      Cochrane approach. Data extraction was performed in a standardised manner by one
      reviewer and rechecked by the other, and where necessary investigators were
      contacted to obtain missing information. A meta-analysis was not undertaken
      because of the heterogeneity of the treatments, procedures and quality of the
      included trials. A narrative overview of the results is therefore presented. MAIN
      RESULTS: Three studies - two randomised controlled trials (RCTs) and one
      controlled clinical trial (CCT) - involving 256 participants satisfied the
      inclusion criteria. One RCT compared Naseptin antiseptic cream with no treatment,
      the second RCT compared Vaseline(R) petroleum jelly with no treatment, and the
      CCT compared Naseptin antiseptic cream with silver nitrate cautery. Overall,
      results were inconclusive, with no statistically significant difference found
      between the compared treatments. No serious adverse effects were reported from
      any of the interventions, although children receiving silver nitrate cautery
      reported that it was a painful experience (despite the use of local anaesthetic).
      REVIEWER'S CONCLUSIONS: The optimal management of children with recurrent
      idiopathic epistaxis is unknown. High quality randomised controlled trials
      comparing interventions either with placebo or no treatment, and with a follow-up
      period of at least a year, are needed to assess the relative merits of the
      various treatments currently in use.

PMID- 14974070
TI  - Calcium supplementation on bone loss in postmenopausal women.
AB  - BACKGROUND: Although calcium is one the simplest and least expensive strategies
      for preventing osteoporotic fractures calcium supplementation is nevertheless not
      without controversy (Kanis 1989; Nordin 1990). The Food and Drug Administration
      in the US has permitted a bone health claim for calcium-rich foods, and the NIH
      in its Consensus Development Process approved a statement that high calcium
      intake reduces the risk of osteoporosis. OBJECTIVES: To assess the effects of
      calcium on bone density and fractures in postmenopausal women. SEARCH STRATEGY:
      We searched Cochrane Controlled Register, MEDLINE and EMBASE up to 2001, and
      examined citations of relevant articles and proceedings of international
      meetings. SELECTION CRITERIA: Trials that randomized postmenopausal women to
      calcium supplementation or usual calcium intake in the diet and reported bone
      mineral density of the total body, vertebral spine, hip, or forearm or recorded
      the number of fractures, and followed patients for at least one year were
      considered for inclusion. DATA COLLECTION AND ANALYSIS: Three independent
      reviewers assessed the methodologic quality and extracted data for each trial.
      For each bone density site (lumbar spine, total body, combined hip and combined
      forearm), we calculated the weighted mean difference in bone density between
      treatment and control groups using the percentage change from baseline. We
      constructed regression models in which the independent variables were year and
      dose, and the dependent variable was the effect size. This regression was used to
      determine the years across which pooling was appropriate. Heterogeneity was
      assessed. For each fracture analysis we calculated a risk ratio. MAIN RESULTS:
      Fifteen trials, representing 1806 participants, were included. Calcium was more
      effective than placebo in reducing rates of bone loss after two or more years of
      treatment. The pooled difference in percentage change from baseline was 2.05%
      (95% CI 0.24 to 3.86) for total body bone density, 1.66% (95% CI 0.92 to 2.39)
      for the lumbar spine at 2 years, 1.60% (95% CI 0.78 to 2.41) for the hip, and
      1.91% (95% CI 0.33 to 3.50) for the distal radius. The relative risk of fractures
      of the vertebrae was 0.79 (95% CI 0.54 to 1.09); the relative risk for non
      vertebral fractures was 0.86 (95% CI 0.43 to 1.72). REVIEWER'S CONCLUSIONS:
      Calcium supplementation alone has a small positive effect on bone density. The
      data show a trend toward reduction in vertebral fractures, but it is unclear if
      calcium reduces the incidence of non vertebral fractures.

PMID- 14974071
TI  - Pin site care for preventing infections associated with external bone fixators
      and pins.
AB  - BACKGROUND: Metal pins are used to apply skeletal traction or external fixation
      devices in the management of orthopaedic fractures. These pins protrude through
      the skin and are therefore described as 'percutaneous' and much has been written
      on the management of the associated skin wound. The way in which percutaneous
      pins are treated may affect the incidence of pin site infection. Recommendations
      for care are not necessarily evidence based. This review set out to summarise the
      research evidence on the effect of pin site care on infection rates. OBJECTIVES:
      To assess the effect on infection rates of different methods of cleansing and
      dressing orthopaedic percutaneous pin sites. SEARCH STRATEGY: The following
      electronic databases were searched: Medline (from 1966), the Cochrane Central
      Register of Controlled Trials (2003 issue 1) and the Wounds Group Specialised
      Trials Register (March 2003). In addition reference lists of review articles and
      relevant trials were also searched and some handsearching undertaken. SELECTION
      CRITERIA: All randomised controlled trials (RCTs) in people comparing the effect
      on infection rates of different methods of cleansing or dressing orthopaedic
      percutaneous pin sites were evaluated. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently assessed the citations retrieved by the search strategies
      for reports of relevant RCTs. MAIN RESULTS: Only one trial was eligible for
      inclusion in the review. Henry (1996) compared cleansing with 0.9% saline,
      cleansing with 70% alcohol and no cleansing and found significantly fewer
      infections in pin sites which had not been cleansed. REVIEWER'S CONCLUSIONS:
      There is very little evidence as to which pin site care regimen best reduces
      infection rates. Clearly there is a need for large RCTs to determine the best
      method of pin site management.

PMID- 14974072
TI  - Drug therapy for anxiety in palliative care.
AB  - BACKGROUND: Anxiety is common among patients with advanced disease. It can be a
      natural response to impending death, but may also result from an underlying
      anxiety disorder, pain, or other untreated or poorly managed symptoms.
      OBJECTIVES: The primary objective of this review was to identify and evaluate
      studies examining medications used to treat patients suffering from anxiety
      during the terminal phases of disease. SEARCH STRATEGY: We searched the following
      sources: MEDLINE (1966 to July 2003), EMBASE (1980 to July 2003), CINAHL (1982 to
      July 2003), PsycLit (1974 to July 2003), PsycInfo (1990 to July 2003), and the
      Cochrane Library (Issue 2, 2003) for literature pertaining to this topic
      published in any language using a detailed search strategy. SELECTION CRITERIA:
      Prospective, randomized trials with or without blinding involving the use of
      pharmacological agents for the treatment of anxiety at the end of life were
      sought. DATA COLLECTION AND ANALYSIS: Six potential studies were identified by
      the search strategy but none met the criteria for inclusion in this review. Two
      of these studies assessed the effectiveness of alprazolam in patients with a
      diagnosis of cancer, but who would not be considered in the end-stage of life.
      MAIN RESULTS: No data were available to enable an assessment to be made of the
      effectiveness of drugs to treat anxiety in palliative care patients. REVIEWER'S
      CONCLUSIONS: There remains insufficient evidence to draw a conclusion about the
      effectiveness of pharmacotherapy for anxiety in terminally ill patients. To date
      no studies were found that met the inclusion criteria for this review.
      Prospective controlled clinical trials are necessary in order to establish the
      benefits and harms of pharmacotherapy for the treatment of anxiety in palliative
      care.

PMID- 14974073
TI  - Single dose oral paracetamol (acetaminophen) for postoperative pain.
AB  - BACKGROUND: Paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs
      (NSAIDs) are widely used for the relief of mild and moderate pain arising from
      headache, musculoskeletal conditions and dysmenorrhoea. A prior Cochrane
      systematic review concluded that paracetamol is also effective for postoperative
      pain, but additional trials have since been published. This review sought to
      evaluate the efficacy and safety of paracetamol using current data, and to
      compare the findings with other analgesics evaluated in the same way. OBJECTIVES:
      To assess the efficacy of single dose oral paracetamol for the treatment of acute
      postoperative pain. SEARCH STRATEGY: We searched the Cochrane Library (Issue 3,
      2002), the trials register of the Cochrane Pain, Palliative and Supportive Care
      group (November 2002); MEDLINE (1966 to May 1996); PubMed (1996 to August 2001);
      EMBASE (1980 to 1996); the Oxford Pain Relief Database (1950 to 1994); and
      reference lists of articles in order to update an existing version of the review.
      SELECTION CRITERIA: Randomised, double-blind, placebo-controlled clinical trials
      of paracetamol for acute postoperative pain in adults. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently assessed trial quality and extracted data.
      The area under the 'pain relief versus time' curve was used to derive the
      proportion of patients with paracetamol or placebo experiencing least 50% pain
      relief over four to six hours using validated equations. The number-needed-to
      treat (NNT) was calculated using 95% confidence intervals. Information on adverse
      effects was also collected. MAIN RESULTS: Forty-seven reports that enrolled 4186
      patients (2561 patients were treated with a single oral dose of paracetamol and
      1625 with placebo) met the inclusion criteria and were included in the analyses.
      The NNTs for at least 50% pain relief over four to six hours following a single
      dose of paracetamol were as follows: 325 mg NNT 3.8 (2.2 to 13.3); 500 mg NNT 3.5
      (2.7 to 4.8); 600/650 mg NNT 4.6 (3.9 to 5.5); 975/1000 mg NNT 3.8 (3.4 to 4.4);
      and 1500 mg NNT 3.7 (2.3 to 9.5). Sub-group analysis showed no significant
      differences between smaller and larger trials, or lower and higher quality
      trials. Drug-related study withdrawals were rarely reported. Studies reported a
      variable incidence of adverse effects that were generally mild and transient.
      There were no statistically significant differences in the frequency of reported
      adverse effects between paracetamol 975/1000 mg and placebo. REVIEWER'S
      CONCLUSIONS: Single doses of paracetamol are effective analgesics for acute
      postoperative pain and give rise to few adverse effects.

PMID- 14974074
TI  - Single dose oral rofecoxib for postoperative pain.
AB  - BACKGROUND: Rofecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor licensed
      in the UK and the US for acute pain treatment and is associated with fewer
      gastrointestinal adverse events than conventional NSAIDs. Rofecoxib is believed
      to be at least as effective as conventional non-steroidal anti-inflammatory drugs
      (NSAIDs) for postoperative pain. OBJECTIVES: To assess the analgesic efficacy and
      adverse effects of a single oral dose of rofecoxib for moderate to severe
      postoperative pain, and to compare its effectiveness with other analgesics used
      for treating acute pain. SEARCH STRATEGY: We searched Cochrane Library (Issue 1,
      2002), MEDLINE (1966 to March 2002), Biological Abstracts (1985 to Dec 2001),
      CINAHL (1982 to Dec 2001), Psychinfo (1967 to Jan 2002), PubMed (March 2001) and
      the Oxford pain database. SELECTION CRITERIA: Randomised controlled trials of
      adult patients who received either rofecoxib or placebo for postoperative pain.
      DATA COLLECTION AND ANALYSIS: Trials were quality scored and the data extracted
      by two reviewers independently. Summed pain relief (TOTPAR) or pain intensity
      difference (SPID) was extracted and converted into dichotomous information
      yielding the number of patients with at least 50% pain relief. These derived
      results were used to calculate the relative benefit (RB) and number-needed-to
      treat (NNT) for one patient to achieve at least 50% pain relief. MAIN RESULTS:
      Seven studies met the inclusion criteria. All the trials were funded by Merck &
      Company, the manufacturer of rofecoxib. In total, 667 patients were treated with
      rofecoxib 50 mg and 315 with placebo. The NNT for rofecoxib 50 mg was 2.2 (95% CI
      1.9 to 2.4), ie, for every two patients treated with rofecoxib 50 mg, one patient
      experienced at least 50% pain relief that would not have done had they received
      placebo. All the studies were of short duration, and reported adverse events
      occurred less frequently with rofecoxib 50 mg than with placebo. REVIEWER'S
      CONCLUSIONS: Rofecoxib 50 mg (a dose 2 to 4 times the standard daily dose for
      chronic pain) is an effective single dose oral analgesic for acute postoperative
      pain.

PMID- 14974075
TI  - Antiplatelet agents for preventing pre-eclampsia and its complications.
AB  - BACKGROUND: Pre-eclampsia is associated with deficient intravascular production
      of prostacyclin, a vasodilator, and excessive production of thromboxane, a
      platelet-derived vasoconstrictor and stimulant of platelet aggregation. These
      observations led to the hypotheses that antiplatelet agents, low-dose aspirin in
      particular, might prevent or delay the development of pre-eclampsia. OBJECTIVES:
      To assess the effectiveness and safety of antiplatelet agents when given to women
      at risk of developing pre-eclampsia. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group trials register (September 2003), the Cochrane
      Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003),
      EMBASE (1994 to 2003) and we handsearched the congress proceedings of the
      International and European Societies for the Study of Hypertension in Pregnancy.
      SELECTION CRITERIA: All randomised trials comparing antiplatelet agents with
      either placebo or no antiplatelet agent during pregnancy. Quasi-random study
      designs were excluded. Participants were pregnant women considered to be at risk
      of developing pre-eclampsia. Interventions were any comparisons of an
      antiplatelet agent (such as low-dose aspirin or dipyridamole) with either placebo
      or no antiplatelet agent. DATA COLLECTION AND ANALYSIS: Two reviewers assessed
      trials for inclusion in the review and extracted data. We entered data into the
      Review Manager software and double checked. MAIN RESULTS: Fifty-one trials
      involving 36,500 women are included in this review. There is a 19% reduction in
      the risk of pre-eclampsia associated with the use of antiplatelet agents ((43
      trials, 33,439 women; relative risk (RR) 0.81, 95% confidence interval (CI) 0.75
      to 0.88); number needed to treat (NNT) 69 (51, 109)).Twenty-eight trials (31,845
      women) reported preterm birth. There is a small (7%) reduction in the risk of
      delivery before 37 completed weeks ((RR 0.93, 95% CI 0.89 to 0.98); NNT 83 (50,
      238)). Fetal or neonatal deaths were reported in 38 trials (34,010 women).
      Overall there is a 16% reduction in baby deaths in the antiplatelet group (RR
      0.84, 95% CI 0.74 to 0.96); NNT 227 (128, 909)). Small-for-gestational age babies
      were reported in 32 trials (24,310 women), with an 8% reduction in risk (RR 0.92,
      95% CI 0.85 to 1.00). There were no significant differences between treatment and
      control groups in any other measures of outcome. REVIEWER'S CONCLUSIONS:
      Antiplatelet agents, in this review largely low-dose aspirin, have small-moderate
      benefits when used for prevention of pre-eclampsia. Further information is
      required to assess which women are most likely to benefit, when treatment is best
      started, and at what dose.

PMID- 14974076
TI  - Complex behavioural and educational interventions for nocturnal enuresis in
      children.
AB  - BACKGROUND: Nocturnal enuresis (bedwetting) is a socially disruptive and
      stressful condition which affects around 15-20% of five year olds, and up to 2%
      of young adults. OBJECTIVES: To assess the effects of complex behavioural and
      educational interventions on nocturnal enuresis in children, and to compare them
      with other interventions. SEARCH STRATEGY: We searched the Cochrane Incontinence
      Group trials register (December 2002) and the reference lists of relevant
      articles. Date of the most recent searches: December 2002. SELECTION CRITERIA:
      All randomised or quasi-randomised trials of complex behavioural or educational
      interventions for nocturnal enuresis in children were included, except those
      focused solely on daytime wetting. Comparison interventions included no
      treatment, simple and physical behavioural methods, alarms, desmopressin,
      tricyclics, and miscellaneous other interventions. DATA COLLECTION AND ANALYSIS:
      Two reviewers independently assessed the quality of the eligible trials, and
      extracted data. MAIN RESULTS: Sixteen trials involving 1081 children were
      identified which included a complex or educational intervention for nocturnal
      enuresis. The trials were mostly small and some had methodological problems
      including the use of a quasi-randomised method of concealment of allocation in
      three trials and baseline differences between the groups in another three.A
      complex intervention (such as dry bed training (DBT) or full spectrum home
      training (FSHT)) including an alarm was better than no-treatment control groups
      (eg RR for failure or relapse after stopping DBT 0.25; 95% CI 0.16 to 0.39) but
      there was not enough evidence about the effects of complex interventions alone if
      an alarm was not used. A complex intervention on its own was not as good as an
      alarm on its own or the intervention supplemented by an alarm (eg RR for failure
      or relapse after DBT alone versus DBT plus alarm 2.81; 95% CI 1.80 to 4.38). On
      the other hand, a complex intervention supplemented by a bed alarm might reduce
      the relapse rate compared with the alarm on its own (eg RR for failure or relapse
      after DBT plus alarm versus alarm alone 0.5; 95% CI 0.31 to 0.80).There was not
      enough evidence to judge whether providing educational information about enuresis
      was effective, irrespective of method of delivery. There was some evidence that
      direct contact between families and therapists enhanced the effect of a complex
      intervention, and that increased contact and support enhanced a package of simple
      behavioural interventions, but these were addressed only in single trials and the
      results would need to be confirmed by further randomised controlled trials, in
      particular the effect on use of resources. REVIEWER'S CONCLUSIONS: Although DBT
      and FSHT were better than no treatment when used in combination with an alarm,
      there was insufficient evidence to support their use without an alarm. An alarm
      on its own was also better than DBT on its own, but there was some evidence that
      combining an alarm with DBT was better than an alarm on its own, suggesting that
      DBT may augment the effect of an alarm. There was also some evidence that direct
      contact with a therapist might enhance the effects of an intervention.

PMID- 14974077
TI  - Therapy with glatiramer acetate for multiple sclerosis.
AB  - BACKGROUND: Some clinical data have shown that glatiramer acetate (Copaxone), a
      synthetic amino acid polymer empirically found to suppress experimental allergic
      encephalomyelitis (EAE), an animal model of MS, might help improve the outcome of
      patients with multiple sclerosis (MS). OBJECTIVES: We performed a Cochrane review
      of all randomised, placebo-controlled trials of glatiramer acetate in MS,
      whatever the disease course. SEARCH STRATEGY: We searched the Cochrane MS Group
      trials register (June 2003), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (Issue 2, 2003), MEDLINE (PubMed) (January 1966 to June 2003), EMBASE
      (January 1988 to June 2003) and hand searching of symposia reports (1990-2002)
      from the neurological Associations and MS Societies in both Europe and America.
      SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing glatiramer
      acetate and placebo in patients with definite MS, whatever the administration
      schedule and disease course, were eligible for this review. DATA COLLECTION AND
      ANALYSIS: Both patients with relapsing-remitting (RR) and chronic progressive
      (CP) MS were analysed. Study protocols were comparable across trials as to
      patient entry criteria and outcome definition. No major flaws were found in
      methodological quality. However, efficacy of blinding should be balanced against
      well-known side effects, including injection-site reactions in glatiramer acetate
      treated patients. MAIN RESULTS: A total of 646 patients contributed to this
      review, as it is summarised in Table 01. Glatiramer acetate did not show any
      significant effect on disease progression, measured as a sustained worsening in
      the Expanded Disability Status Scale (EDSS). On the other hand, a slight decrease
      in the mean EDSS score, driven by a major study, should be considered in the
      light of the limited validity of this outcome measure. No benefit was shown in CP
      MS patients (progression at two years: RR=0.69, 95% CI [0.33 to 1.46]). The
      frequency of reported adverse events does not support any major toxicity
      associated with glatiramer acetate administration. The most common systemic
      adverse event was a transient and self-limiting patterned reaction of flushing,
      chest tightness, sweating, palpitations, anxiety (relative risk = 3.40 (95% CI
      [2.22 to 5.21], p <0.00001]). Local injection-site reactions were observed in up
      to a half of patients treated with glatiramer acetate, thus making a blind
      assessment of outcomes questionable. REVIEWER'S CONCLUSIONS: Glatiramer acetate
      did not show any beneficial effect on the main outcome measures in MS, i.e.
      disease progression, and it does not substantially affect the risk of clinical
      relapses. Therefore its routine use in clinical practice is not currently
      supported. More investigations are needed. Further research should also develop
      more reliable measures of patient disability over time and include quality of
      life among primary outcomes.

PMID- 14974078
TI  - Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA
      hydroxylase (PHYH) and the PTS2 receptor (PEX7).
AB  - Refsum disease has long been known to be an inherited disorder of lipid
      metabolism characterized by the accumulation of phytanic acid (3,7,11,15
      tetramethylhexadecanoic acid) caused by an alpha-oxidation deficiency of this
      branched chain fatty acid in peroxisomes. The mechanism of phytanic acid alpha
      oxidation and the enzymes involved had long remained mysterious, but they have
      been resolved in recent years. This has led to the resolution of the molecular
      basis of Refsum disease. Interestingly, Refsum disease is genetically
      heterogeneous; two genes, PHYH (also named PAHX) and PEX7, have been identified
      to cause Refsum disease, as reviewed in this work.

PMID- 14974079
TI  - Gross Rearrangement Breakpoint Database (GRaBD).
AB  - Translocations and gross gene deletions are an important cause of both cancer and
      inherited disease. Such DNA rearrangements are nonrandomly distributed in the
      human genome as a consequence of selection for growth advantage and/or the
      inherent potential of some DNA sequences to be particularly susceptible to
      breakage and recombination. The Gross Rearrangement Breakpoint Database (GRaBD;
      http://www.uwcm.ac.uk/uwcm/mg/grabd/) was established primarily for the analysis
      of the sequence context of translocation and deletion breakpoints in a search for
      characteristics that might have rendered these sequences prone to rearrangement.
      GRaBD, which contains 397 germline and somatic DNA breakpoint junction sequences
      derived from 219 different rearrangements underlying human inherited disease and
      cancer, is the only comprehensive collection of gross gene rearrangement
      breakpoint junctions currently available.

PMID- 14974080
TI  - The role of cathepsin C in Papillon-Lefevre syndrome, prepubertal periodontitis,
      and aggressive periodontitis.
AB  - We have previously reported that loss-of-function mutations in the cathepsin C
      gene (CTSC) result in Papillon-Lefevre syndrome, an autosomal recessive condition
      characterized by palmoplantar keratosis and early-onset, severe periodontitis.
      Others have also reported CTSC mutations in patients with severe prepubertal
      periodontitis, but without any skin manifestations. The possible role of CTSC
      variants in more common types of non-mendelian, early-onset, severe periodontitis
      ("aggressive periodontitis") has not been investigated. In this study, we have
      investigated the role of CTSC in all three conditions. We demonstrate that PLS is
      genetically homogeneous and the mutation spectrum that includes three novel
      mutations (c.386T>A/p.V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS
      families (including eight from our previous study) provides an insight into
      structure-function relationships of CTSC. Our data also suggest that a complete
      loss-of-function appears to be necessary for the manifestation of the phenotype,
      making it unlikely that weak CTSC mutations are a cause of aggressive
      periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects
      with aggressive periodontitis and age-sex matched controls, which demonstrated
      that there was no significant difference between these two groups (1,728.7 +/- SD
      576.8 micro moles/mg/min vs. 1,678.7 +/- SD 527.2 micro moles/mg/min,
      respectively, p = 0.73). CTSC mutations were detected in only one of two families
      with prepubertal periodontitis; these did not form a separate functional class
      with respect to those observed in classical PLS. The affected individuals in the
      other prepubertal periodontitis family not only lacked CTSC mutations, but in
      addition did not share the haplotypes at the CTSC locus. These data suggest that
      prepubertal periodontitis is a genetically heterogeneous disease that, in some
      families, just represents a partially penetrant PLS.

PMID- 14974081
TI  - Mutational analysis of mucopolysaccharidosis type VI patients undergoing a trial
      of enzyme replacement therapy.
AB  - Mucopolysaccharidosis type VI (MPS VI), or Maroteaux-Lamy syndrome, is a
      lysosomal storage disorder caused by a deficiency of N-acetylgalactosamine-4
      sulfatase (ARSB). Seven MPS VI patients were chosen for the initial clinical
      trial of enzyme replacement therapy. Direct sequencing of genomic DNA from these
      patients was used to identify ARSB mutations. Each individual exon of the ARSB
      gene was amplified by PCR and subsequently sequenced. Nine substitutions
      (c.289C>T [p.Q97X], c.629A>G [p.Y210C], c.707T>C [p.L236P], c.936G>T [p.W312C],
      c.944G>A [p.R315Q], c.962T>C [p.L321P], c.979C>T [p.R327X], c.1151G>A [p.S384N],
      and c.1450A>G [p.R484G]), two deletions (c.356_358delTAC [p.Y86del] and
      c.427delG), and one intronic mutation (c.1336+2T>G) were identified. A total of 7
      out of the 12 mutations identified were novel (p.Y86del, p.Q97X, p.W312C,
      p.R327X, c.427delG, p.R484G, and c.1336+2T>G). Two of these novel mutations
      (p.Y86del and p.W312C) were expressed in Chinese hamster ovary cells and analyzed
      for residual ARSB activity and mutant ARSB protein. The two common polymorphisms
      c.1072G>A [p.V358M] and c.1126G>A [p.V376M] were identified among the patients,
      along with the silent mutation c.1191A>G. Cultured fibroblast ARSB mutant protein
      and residual activity were determined for each patient, and, together with
      genotype information, were used to predict the expected clinical severity of each
      MPS VI patient.

PMID- 14974082
TI  - Large deletions of the MECP2 gene detected by gene dosage analysis in patients
      with Rett syndrome.
AB  - MECP2 mutations are responsible for Rett syndrome (RTT). Approximately a quarter
      of classic RTT cases, however, do not have an identifiable mutation of the MECP2
      gene. We hypothesized that larger deletions arising from a deletion prone region
      (DPR) occur commonly and are not being routinely detected by the current PCR
      mediated screening strategies. We developed and applied a quantitative PCR
      strategy (qPCR) to samples referred for diagnostic assessment from 140 patients
      among whom RTT was strongly suspected and from a second selected group of 31
      girls with classical RTT. Earlier MECP2 mutation screening in both groups of
      patients had yielded a wild-type result. We identified 10 large deletions (7.1%)
      within the first group and five deletions in the second group (16.1%). Sequencing
      of the breakpoints in 11 cases revealed that eight cases had one breakpoint
      within the DPR. Among seven cases, the breakpoint distant to the DPR involved one
      of several Alu repeats. Sequence analysis of the junction sequences revealed that
      eight cases had complex rearrangements. Examination of the MECP2 genomic sequence
      reveals that it is highly enriched for repeat elements, with the content of Alu
      repeats rising to 27.8% in intron 2, in which there was an abundance of
      breakpoints among our patients. Furthermore, a perfect chi sequence, known to be
      recombinogenic in E. coli, is located in the DPR. We propose that the chi
      sequence and Alu repeats are potent factors contributing to genomic
      rearrangement. We suggest that routine mutation screening in MECP2 should include
      quantitative analysis of the genomic sequences flanking the DPR.

PMID- 14974083
TI  - APECED-causing mutations in AIRE reveal the functional domains of the protein.
AB  - A defective form of the AIRE protein causes autoimmune destruction of target
      organs by disturbing the immunological tolerance of patients with a rare
      monogenic disease, autoimmune polyendocrinopathy (APE)-candidiasis (C)-ectodermal
      dystrophy (ED), APECED. Recently, experiments on knockout mice revealed that AIRE
      controls autoimmunity by regulating the transcription of peripheral tissue
      restricted antigens in thymic medullary epithelial cells. Thus, AIRE provides a
      unique model for molecular studies of organ-specific autoimmunity. In order to
      analyze the molecular and cellular consequences of 16 disease-causing mutations
      in vitro, we studied the subcellular localization, transactivation capacity,
      homomultimerization, and complex formation of several mutant AIRE polypeptides.
      Most of the mutations altered the nucleus-cytoplasm distribution of AIRE and
      disturbed its association with nuclear dots and cytoplasmic filaments. While the
      PHD zinc fingers were necessary for the transactivation capacity of AIRE, other
      regions of AIRE also modulated this function. Consequently, most of the mutations
      decreased transactivation. The HSR domain was responsible for the
      homomultimerization activity of AIRE; all the missense mutations of the HSR and
      the SAND domains decreased this activity, but those in other domains did not. The
      AIRE protein was present in soluble high-molecular-weight complexes. Mutations in
      the HSR domain and deletion of PHD zinc fingers disturbed the formation of these
      complexes. In conclusion, we propose an in vitro model in which AIRE
      transactivates transcription through heteromeric molecular interactions that are
      regulated by homomultimerization and conditional localization of AIRE in the
      nucleus or in the cytoplasm.

PMID- 14974084
TI  - A nicotine C-oxidase gene (CYP2A6) polymorphism important for promoter activity.
AB  - In humans, several polymorphic variants have been described for the gene encoding
      the major nicotine C-oxidase, cytochrome P450 2A6 (CYP2A6), which is to a great
      extent responsible for the large interindividual differences seen at the
      enzymatic and activity levels. Hitherto, mainly polymorphic variants in the open
      reading frame have been identified. In the present study, we identified a novel
      single nucleotide polymorphism (SNP) located in the 5' flanking region of the
      CYP2A6 gene. Sequencing of 1.4 kb of the 5'-upstream region of the CYP2A6 gene
      from eight individuals revealed a c.-1013A>G polymorphism defining two new
      alleles, CYP2A6*1D and CYP2A6*1E, lacking or having also the CYP2A7 3'-UTR.
      Analysis of genomic DNA from 32 Swedish and 109 Turkish subjects by dynamic
      allele-specific hybridization (DASH) showed that, in both groups, the variants
      carrying the c.-1013A>G SNP represent approximately 70% of the total number of
      alleles. Transfection of HepG2 cells with luciferase reporter constructs
      containing 1019 bp of the CYP2A6 5'-regulatory sequence showed that the region
      between c.-1005 and c.-1019 elicited a strong enhancer effect and that the
      CYP2A6*1D promoter had significantly reduced expression as compared to CYP2A6*1A
      carrying c.-1013A. Electrophoretic mobility shift assays (EMSA) showed that
      nuclear proteins from HepG2 and B16A2 cells exhibited a higher binding affinity
      to the probe harboring c.-1013A as compared to the c.-1013G probe, although the
      transcription factor(s) responsible for this binding could not be identified. In
      conclusion, our results indicate the presence of a strong enhancer or promoter
      responsive element between c.-1005 and c.-1019 in the CYP2A6 gene and that a c.
      1013A>G polymorphism in this region affects CYP2A6 transcription.

PMID- 14974085
TI  - Noonan syndrome-associated SHP2/PTPN11 mutants cause EGF-dependent prolonged GAB1
      binding and sustained ERK2/MAPK1 activation.
AB  - Noonan syndrome is a developmental disorder with dysmorphic facies, short
      stature, cardiac defects, and skeletal anomalies, which can be caused by missense
      PTPN11 mutations. PTPN11 encodes Src homology 2 domain-containing tyrosine
      phosphatase 2 (SHP2 or SHP-2), a protein tyrosine phosphatase that acts in signal
      transduction downstream to growth factor, hormone, and cytokine receptors. We
      compared the functional effects of three Noonan syndrome-causative PTPN11
      mutations on SHP2's phosphatase activity, interaction with a binding partner, and
      signal transduction. All SHP2 mutants had significantly increased basal
      phosphatase activity compared to wild type, but that activity varied
      significantly between mutants and was further increased after epidermal growth
      factor stimulation. Cells expressing SHP2 mutants had prolonged extracellular
      signal-regulated kinase 2 activation, which was ligand-dependent. Binding of SHP2
      mutants to Grb2-associated binder-1 was increased and sustained, and tyrosine
      phosphorylation of both proteins was prolonged. Coexpression of Grb2-associated
      binder-1-FF, which lacks SHP2 binding motifs, blocked the epidermal growth factor
      mediated increase in SHP2's phosphatase activity and resulted in a dramatic
      reduction of extracellular signal-regulated kinase 2 activation. Taken together,
      these results document that Noonan syndrome-associated PTPN11 mutations increase
      SHP2's basal phosphatase activity, with greater activation when residues directly
      involved in binding at the interface between the N-terminal Src homology 2 and
      protein tyrosine phosphatase domains are altered. The SHP2 mutants prolonged
      signal flux through the RAS/mitogen-activated protein kinase (ERK2/MAPK1) pathway
      in a ligand-dependent manner that required docking through Grb2-associated binder
      1 (GAB1), leading to increased cell proliferation.

PMID- 14974086
TI  - Analysis of CBP (CREBBP) gene deletions in Rubinstein-Taybi syndrome patients
      using real-time quantitative PCR.
AB  - Rubinstein-Taybi syndrome (RTS) is a well-defined syndrome characterized by
      facial abnormalities, broad thumbs, broad big toes, and growth and mental
      retardation as the main clinical features. RTS was shown to be associated with
      disruption of the CREB-binding protein gene CBP (CREBBP), either by gross
      chromosomal rearrangements or by point mutations. Translocations and inversions
      involving chromosome band 16p13.3 form the minority of CBP mutations, whereas
      microdeletions occur more frequently (about 10%). Most deletion studies in RTS
      are performed by FISH analysis, and five cosmids must be used to cover the whole
      of the CBP gene, which spreads over 150 kb. Here we report the design of gene
      dosage assays by real-time quantitative PCR that are targeted on three exons
      located respectively at the 5' end (exon 2), in the middle (exon 12), and at the
      3' end (exon 30) of the CBP gene. This technique proved to be efficient and
      powerful in finding deletions and complementary to the other available
      techniques, since it allowed us to identify deletions at the 3' end of the gene
      that had been missed by FISH analysis, and to refine some deletion breakpoints.
      Our results therefore suggest that real-time quantitative PCR is a useful
      technique to be included in the deletion search in RTS patients.

PMID- 14974087
TI  - Eight novel MSH6 germline mutations in patients with familial and nonfamilial
      colorectal cancer selected by loss of protein expression in tumor tissue.
AB  - Germline mutations in mismatch repair (MMR) genes, predominantly in MLH1 and
      MSH2, are responsible for hereditary nonpolyposis colorectal cancer (HNPCC), a
      cancer-susceptibility syndrome with high penetrance. In addition, MSH6 mutations
      have been reported to account for about 10% of all germline mismatch repair (MMR)
      gene mutations in HNPCC patients, and have been associated with a later age of
      onset of the disease compared to MLH1 and MSH2 mutations. Here, we report eight
      novel germline mutations in MSH6. The patients were selected by having developed
      tumors with loss of MSH6 protein expression. All tumors showed high-level
      microsatellite instability (MSI-H). Seven mutations resulted in premature stop
      codons, comprised of two nonsense mutations (c.426G>A [p.W142X], c.2105C>A
      [p.S702X]), two insertions (c.2611_2614dupATTA [p.I872fsX10], c.3324dupT
      [p.I1109fsX3]) and three deletions (c.1190_1191delAT [p.Y397fsX3],
      c.1632_1635delAAAA [p.E544fsX26], c.3513_3514delTA [p.1171fsX5]). In addition, an
      amino acid substitution of an arginine residue (c.2314C>T [p.R772W]) conserved
      throughout a wide variety of mutS homologs has been found in a patient not
      fulfilling the Bethesda criteria for HNPCC. Our results emphasize the suitability
      of IHC as a pre-selection tool for MSH6 mutation analysis and the high frequency
      of germline mutation detection in patients with MSH6-deficient tumors. In
      addition, our findings point towards a broad variability regarding penetrance
      associated with MSH6 germline mutations.

PMID- 14974088
TI  - Molecular characterization of familial hypercholesterolemia in German and Greek
      patients.
AB  - We used the denaturing gradient gel electrophoresis (DGGE) method to define
      mutations in the promoter region, the 18 exons, and their flanking intronic
      sequences of the low-density lipoprotein (LDL) receptor gene LDLR, causing
      familial hypercholesterolemia (FH) phenotype in 100 German and in 100 Greek
      hypercholesterolemic individuals. In addition, we tested all patients for the
      presence of mutations in codons 3456-3553 of the gene encoding apolipoprotein B
      100 (APOB). Twenty-six aberrant DGGE patterns were identified and subsequently
      directly sequenced. In LDLR, two novel missense mutations (c.1957G>T/p.V653F,
      c.647 G>A/p.C216Y) and one novel homozygous base substitution c.1-156 C>T in the
      repeat 2 of the promoter region were identified among German FH patients; one
      novel splice site c.1060+10C>G was identified among Greek FH patients. One of the
      German FH patients was a carrier for the mutations c.1171G>A/p.A391T and p.V653F,
      and two of the Greek FH patients were compound heterozygotes for the mutations
      c.1150C>T/p.Q384X and c.1158C>G/p.D386E. Two German FH patients carried the
      mutation p.R3500Q within APOB. Comparing the mutations within the LDLR gene of
      the two European FH populations, the German population seems to be more
      heterogeneous than the Greek cohort. Further studies in progress are trying to
      elucidate the responsiveness to drug therapy in association with LDLR genotype
      and the nutritional habits of the two FH populations.

PMID- 14974089
TI  - BTK: 22 novel and 25 recurrent mutations in European patients with X-linked
      agammaglobulinemia.
AB  - X linked agammaglobulinemia (XLA) is an immunodeficiency disease caused by
      mutations in the gene coding for Bruton's agammaglobulinemia tyrosine kinase
      (BTK), that is involved in signal transduction pathways regulating survival,
      activation, proliferation, and differentiation of B lineage lymphoid cells. XLA
      is a primary immunodeficiency disorder characterized by lack of mature,
      circulating B lymphocytes, and recurrent infections. Using Single Strand
      Conformation Polymorphism (SSCP) followed by direct sequencing we investigated 57
      patients with XLA phenotype, with or without a positive family history, from 52
      unrelated families enrolled in the Italian XLA Multicenter Clinical Study. We
      have identified 25 recurrent mutations, 22 novel mutations including one large
      deletion comprising the coding sequence from exon 11 to 18. Among the mutations
      identified, three were detected in different unrelated families, whereas all the
      others were private mutations.

PMID- 14974090
TI  - A homozygous GJA1 gene mutation causes a Hallermann-Streiff/ODDD spectrum
      phenotype.
AB  - Oculodentodigital dysplasia (ODDD) and Hallermann-Streiff syndrome (HSS) share
      several clinical characteristics. However, while ODDD is a dominantly inherited
      disorder due to mutations in the connexin 43 gene GJA1, the inheritance pattern
      of the HSS syndrome is still debated. Overlapping phenotypes have been described.
      In one of such cases we found a homozygous change at the very conserved R76 codon
      (c.227G>A, p.R76H), the clinically normal parents being heterozigous carriers of
      the same mutation. A different base change at the same codon (p.R76S) leads to a
      complete dominant ODDD phenotype. A case of full-blown HSS phenotype was also
      analysed but GJA1 mutations were not found. GJA1 homozygous hypomorphic mutations
      can result in a phenotype in the HSS/ODDD spectrum.

PMID- 14974091
TI  - Novel androgen receptor gene mutations in Australian patients with complete
      androgen insensitivity syndrome.
AB  - We have identified androgen receptor (AR) gene mutations in eight Australian
      subjects with complete androgen insensitivity syndrome (AIS). Four individuals,
      from three families, have novel mutations that introduce premature termination
      codons. Two siblings have the nonsense mutation Glu681X, and another subject has
      the nonsense mutation p.Ser884X. The other subject has a CA insertion at codon
      829 (c.2847_2848insCA), causing a frameshift mutation that introduces four
      nonsense amino acids prior to a Stop codon. All the termination codons occur in
      the ligand binding domain, and cause reduced androgen binding in patient genital
      skin fibroblasts. Four further patients have missense mutations. One subject has
      two different mutations, p.Ala645Asp in the hinge region of the receptor, and
      p.Arg752Gln in the ligand binding domain. Both these mutations have previously
      been reported in patients with AIS, but the combination of these two mutations in
      one subject is unique. Another subject has a novel c.2533G>C transversion at the
      first nucleotide in exon 5, introducing the amino acid change p.Gly724Ala at a
      highly conserved residue in the ligand binding domain. Androgen binding is normal
      in fibroblasts from this subject, although other point mutations at this amino
      acid totally abolish binding. Two other subjects have mutations previously
      described as causing AIS, namely p.Arg779Trp and p.Val889Met substitutions in the
      ligand binding domain of the receptor. The p.Arg779Trp mutation is associated
      with the detection of a truncated AR protein in this patient's fibroblasts,
      suggesting the mutation renders the receptor susceptible to proteolysis.

PMID- 14974093
TI  - Fenestration of the superior medullary velum as treatment for a trapped fourth
      ventricle: a feasibility study.
AB  - We developed a novel approach for fenestration of the trapped fourth ventricle
      utilizing the superior medullary velum (valve of Vieussens). Trapped fourth
      ventricles, which are seen often in the pediatric hydrocephalic population, are
      troublesome entities surgically. A right burr hole was carried out in 10 adult
      cadavers with no gross intracranial pathology and the superior medullary velum
      was fenestrated to the quadrigeminal cistern with the aid of an endoscope. This
      technique was carried out easily in all cadaveric specimens. With endoscopy, no
      vascular insult was appreciated either before or after fenestration of the
      superior medullary velum. These preliminary findings demonstrate that
      fenestration of the superior medullary velum may provide a good alternative to
      the present therapy of shunting trapped fourth ventricles, a therapy wrought with
      complications.

PMID- 14974094
TI  - Distribution pattern of the human lingual nerve.
AB  - The tongue is an intricate organ with many functions. Despite the knowledge of
      the presence of muscular and neural connections in the tongue, a detailed
      neuroanatomical depiction of the nerves' topography in the tongue has not been
      demonstrated. The topography, branching patterns and neuronal interconnections of
      the lingual nerve were studied in five postmortem human tongues. They were
      stained with Sihler's stain, a technique that renders most of the tongue tissue
      translucent while counterstaining nerves. The lingual nerve reaches the tongue
      posterolaterally. There are two main branches off of the main trunk: the medial
      branch sends 2-4 small branches to the medial part of the ventrolateral tongue
      and the lateral branch runs along the lateral tongue border and sends 3-4 large
      branches to the anterior tip of tongue. Each subdivision gives off 2-5 distal
      branches. Both medial and lateral branches have interconnections with the
      proximal part of the hypoglossal nerve. One of the unexpected discoveries in this
      study was the high density of nervous fibers in the lateral aspect of the tongue
      as compared to the midline region. The average diameter of the main trunk of the
      lingual nerve is 3.5 mm. The medial and lateral branches average 1 mm in
      diameter, the more distal subdivisions measure 0.5-0.75 mm, and the lingual
      hypoglossal interconnections measure 0.125-0.250 mm. In summary, this study
      provides the first detailed depiction of the topography of the human lingual
      nerve and its branches in situ, confirmation of lingual-hypoglossal nerve
      connection, and the first depiction of the high density of lingual nerve
      innervation in the lateral tongue.

PMID- 14974095
TI  - Morphological studies for retrusive movement of the human adult tongue.
AB  - This study identified the anatomical and close functional relationship between
      the transverse lingual and superior pharyngeal constrictor muscle. Two en bloc
      samples (including the tongue and mid-pharyngeal wall) and four whole tongues
      were obtained from adult human cadavers. We found that fibers of the superior
      pharyngeal constrictor muscle connected with fibers of the transverse lingual
      muscle, forming a ring of muscle at the base of the tongue. The average diameters
      of the transverse muscle fibers increased in size gradually as they approached
      the base of the tongue. Distribution of the muscle spindles in the transverse
      lingual muscle and the genioglossus muscle also increased as they reached
      posteriorly near the base of the tongue. These findings suggest that a ring of
      muscle formed by the postero-inferior portion of the transverse lingual muscle
      and the superior pharyngeal constrictor may be largely responsible for the
      retrusive movement of the tongue and the constrictive movement of the pharyngeal
      cavity as an antagonist of the genioglossus muscle.

PMID- 14974096
TI  - Development of the sensory nerves to the dorsum of the tongue in staged human
      embryos.
AB  - To determine in selected, staged human embryos the time period and manner of
      formation of the sensory nerves to the mucosa on the dorsum of the tongue,
      cranial nerves V(3) and IX and their lingual branches were traced
      microscopically. These two cranial nerves along with cranial nerve VII are
      present in the dorsal part of their respective pharyngeal arch 1, 2, and 3 at
      Stage 13. All three nerves grow ventrally at Stage 16, and the lingual branches
      of V(3) and IX become closer to the developing tongue region. The lingual fibers
      begin to enter the tongue substance at Stage 17 when they appear as large short
      branches that terminate 100-400 microm from the dorsal mucosal basement membrane;
      of the fibers that are in the tissue deep to the surface mucosa, those in the
      posterior tongue segment terminate the closest and those in the anterior segment
      the farthest. Chorda tympani nerve fibers are joined with V(3) at Stage 20. At
      this stage nerve fibers reach the basement membrane in the posterior tongue
      segment and by Stage 23 they terminate at the basement membrane throughout the
      tongue, being sparsest in the anterior segment. Primordial papillae appear as
      small mucosal projections throughout the tongue at Stage 20 and are innervated by
      Stage 23. The study found that innervation to the dorsum of the tongue develops
      during the second month of prenatal life. During the 4-week period, Stages 13-23,
      an innervation pattern was observed based on the relative time fibers terminate
      at the basement membrane. The pattern begins caudally in the root, then moves
      rostrally lateral to the middle tongue segment, proceeding then to the tip of the
      tongue. The last area to become innervated is the medial part of the middle
      segment or central portion of the tongue.

PMID- 14974097
TI  - Intrabony course of the inferior alveolar nerve in the edentulous mandible.
AB  - The purpose of this study was to investigate the vertical positioning and
      intrabony branching patterns of the inferior alveolar nerve (IAN) in 39
      edentulous human cadaveric mandibles by buccal microdissection. Dissected
      mandibles were classified on the basis of the height of the IAN within the body
      of the mandible and the branching pattern of the IAN. The IAN was located in the
      superior part of the body of the mandible in 30.7% (12/39) of cases, all of which
      showed a small posterior molar plexus of branches. In 69.2% (27/39) of cases the
      IAN was half-way or closer to the inferior border of the mandible. Of these
      latter cases, 41% demonstrated a small, posterior molar plexus of branches, 37%
      showed posterior and anterior plexuses, and 22% showed either no branches or a
      single trunk with a small number of single branches directed at the superior
      border of the mandible. These findings were rendered in 3D computer format for
      instructional purposes.

PMID- 14974098
TI  - In vivo 3D analysis of the adipose tissue in the orbital apex and the
      compartments of the parasellar region.
AB  - As tissue dissections carried out on formaldehyde-fixed anatomical specimens
      demonstrate, the parasellar region (PSR), traditionally referred to as the
      cavernous sinus, is composed of three distinct compartments: orbital,
      pterygopalatine, and lateral sellar. The aim of our study was to identify and
      measure these compartments in the living and to describe the topography of their
      adipose body tissues. For this purpose data sets of 35 patients, who had
      undergone thin-section multislice computed tomography (CT), were examined using
      3D-reconstruction software. The pterygopalatine and orbital compartments of the
      PSR could be identified in the images by their adipose bodies. We provide more
      exacting measurements of their size than have been presented in earlier studies.
      Furthermore, we include data about the uni- and bilateral presence of the single
      compartments and analyze the topography of the adipose tissue bodies in the
      orbital apex region. Our quantitative data and topographical descriptions confirm
      the compartmentalization concept of the PSR, allow for correct interpretation of
      CT scans of the orbital apex and anterior PSR, and provide baseline information
      for individual planning of surgical and radiological interventions.

PMID- 14974099
TI  - Fossa navicularis: anatomic variation at the skull base.
AB  - The fossa navicularis is a relatively rare anatomic variation of the skull base.
      Awareness of its existence will avoid misinterpretations of radiological images
      and unnecessary investigations. This study describes the appearance of the fossa
      navicularis, and investigates its incidence and whether it is related to
      pathology at the basiocciput. We studied 492 dry human skulls and 525 computer
      tomography (CT) images of patients. Dry skulls showing a fossa navicularis were
      investigated by CT scan, whereas patients identified as having a fossa
      navicularis were further examined with magnetic resonance imaging (MRI). To
      document the position of the fossa more precisely, measurements were made between
      the fossa navicularis and certain anatomic landmarks such as the foramen ovale,
      the pharyngeal tubercle, the posterior border of the vomer, the foramen lacerum,
      the carotid canal, and the occipital condyle. Upon examination, 26 of 492 skulls
      (5.3%) were found to have a fossa navicularis. Twelve were <2 mm in depth and the
      other 14 had a depth of >/=2 mm. Of the 525 patients, 16 (3.0%) were identified
      as having a fossa navicularis in CT images. Evaluation of MRIs showed no soft
      tissue lesions in any of these patients. Comprehensive anatomic details of the
      fossa navicularis have not been reported in the literature. The results of this
      study may be useful to radiologists, anatomists, and surgeons interested in the
      skull base.

PMID- 14974100
TI  - Anatomy of the pelvic plexus and innervation of the prostate gland.
AB  - We have examined the anatomy of the pelvic (inferior hypogastric) plexus in six
      male cadavers, paying particular attention to gross anatomical landmarks that
      might aid in locating it and have used immunohistochemistry to study the small
      branches of the plexus that supply the prostate gland. The pelvic plexus was
      found two finger breadths lateral to the third anterior sacral foramina, lying
      deep to a line drawn from third sacral vertebra, the conventional level of the
      recto-sigmoid junction, and the palpable posterior superior surface of the pubic
      symphysis. Immunohistochemical staining showed small nerve branches from the
      pelvic plexus entering the prostate gland and the presence of ganglia within the
      prostate gland that contained both tyrosine hydroxylase positive and negative
      neuronal cell bodies. This information may be useful in nerve-sparing surgical
      procedures and in discussions of the functional implications of perturbations of
      prostate innervation.

PMID- 14974101
TI  - Kinematics of the toe touching test: an investigation using motion analysis.
AB  - We describe a technique for measuring dynamic motion at the low back along with
      the major lower limb joints during the toe touching maneuver. This type of motion
      analysis was carried out on eight normal volunteers. Flexion during the toe
      touching maneuver involves not only low back and hip movement but also ankle
      plantar flexion and a varying degree of knee movement. The low back and ankle
      movements were highly correlated within each subject to an extent that suggests a
      functional connection between the lower limb and low back movements. The
      significance of our work is two-fold. First, we emphasize that the toe touching
      test represents a combined movement of the low back, the hips, the knees, and the
      ankles and it is reasonable to suggest that abnormalities of these joints may
      affect the clinical relevance of the test as an indicator of back movement.
      Second, we point out that the guidelines of the American Medical Association in
      using the test to determine hip movement are incorrect as they do not take into
      account the effect of knee and ankle movements on the estimation of hip movement.

PMID- 14974102
TI  - Variant of the coracobrachialis muscle with a tunnel for the median nerve and
      brachial artery.
AB  - This case report documents a variation in the insertion of the coracobrachialis
      muscle of the right arm of an adult male cadaver of unknown age. In addition to
      the normal insertion of the coracobrachialis muscle into the middle of the medial
      border of the humerus, an additional slender tendon passed inferiorly, crossing
      anterior to the median nerve and brachial artery before attaching to the medial
      epicondyle of the humerus. Most of the proximal part of the tendon gave rise to
      an aponeurotic expansion that inserted into the distal medial border of the
      humerus. The tendinous insertion and aponeurotic expansion may represent a
      variant of the coracobrachialis longus (Wood's) muscle and the internal brachial
      ligament, respectively. The median nerve and brachial artery traversed a tunnel
      bounded by the additional tendon and aponeurotic expansion as well as the usual
      humeral insertion of the coracobrachialis muscle. The clinical implication of
      this variation is that it may be a cause of median nerve entrapment and brachial
      artery compression.

PMID- 14974103
TI  - Effects of an alternate dissection schedule on gross anatomy laboratory practical
      performance.
AB  - The current medical curricula reform that is taking place in many medical schools
      throughout the world has resulted in less time for gross anatomy laboratory
      instruction. In response, anatomists are using a variety of approaches (e.g.,
      peer teaching, prosections, plastinated anatomical models, etc.) to adapt to
      these changes. To accommodate recent curricular reform at the University of
      Health Sciences College of Osteopathic Medicine, an alternating dissection
      schedule was implemented. The purpose of this study is to examine the effects of
      the alternating schedule on gross anatomy laboratory practical performance. Using
      a Mann-Whitney Rank Sum test, back and upper limb (back-upper limb), and lower
      extremity laboratory practical performance for students who dissected in every
      laboratory (EL group; n = 227) is compared to students who dissected in every
      other laboratory (EOL group; n = 254). For the back-upper limb part of the
      anatomy laboratory practical, the mean percentage scores for the EL and EOL
      groups were 74.5% and 68.1%, respectively (P < 0.001). The mean percentage scores
      for the EL and EOL groups on the lower limb portion of the anatomy lab practical
      were 75.9% and 75.6%, respectively (P = 0.994). These data suggest that the use
      of an alternating dissection schedule had an equivocal effect on the students'
      gross anatomy laboratory practical performance for these two sections. The
      reasons for these conflicting results may have been related to regional
      complexity or volume of information, and the sequence in which the regions were
      taught.

PMID- 14974104
TI  - Unilateral double axillary artery.

PMID- 14974107
TI  - Dorsal and ventral portions of ligamentum nuchae are not independent of each
      other.

PMID- 14974108
TI  - Crista aortae ascendentis, ascending aortic fold or Rindfleisch's fold-an enigma.

PMID- 14974110
TI  - Maternal education modifies the age-related increase in the birth prevalence of
      Down syndrome.
AB  - OBJECTIVE: To test the hypothesis that the age-related increase in the birth
      prevalence of Down syndrome is less for women with higher levels of education due
      to their more frequent use of prenatal diagnosis. METHODS: We compared the
      effects of maternal age on the odds of Down syndrome at birth, and on
      amniocentesis use, in women with <12 years of education with those who had >or=12
      years of education. We used a national data set and analyzed the effects of
      education separately for African Americans (N = 1643054), and non-Hispanic whites
      (N = 6676885) in the US birth cohorts of 1989-1991. Analyses included Mantel
      Haenszel and logistic regression models with the likelihood ratio test to assess
      interactions between education and age effects. RESULTS: For both African
      Americans and non-Hispanic whites, the age-related increase in the odds of Down
      syndrome was substantially less for women with higher levels of education (p <
      0.001). For both ethnic groups, women with higher levels of education were more
      likely to use amniocentesis (p < 0.001). CONCLUSIONS: Our results suggest that
      women with higher levels of education are more likely to use prenatal diagnosis.
      Moreover, this effect of education on prenatal diagnosis use, translates into a
      lower rate of age-related increase in the birth prevalence of Down syndrome.

PMID- 14974111
TI  - Fetal DNA in maternal plasma as a screening variable for preeclampsia. A
      preliminary nonparametric analysis of detection rate in low-risk nonsymptomatic
      patients.
AB  - OBJECTIVE: Our objective was to examine whether plasma fetal DNA can be used as a
      screening variable in those women who developed preeclampsia but without any
      clinical symptom at the time of blood draw. METHODS: Fetal DNA was extracted from
      1.5-mL plasma samples, and the DYS14 gene was analyzed by real-time quantitative
      polymerase chain reaction. Plasma collected and frozen from six women were each
      paired with five matched control samples of identical specimen type from gravid
      women carrying a presumed normal male fetus. Matched rank-sum analysis and
      nonparametric receiver operating characteristic (ROC) curves analysis of
      estimated multiples of median (MoM) were used for calculating detection rate (DR)
      and false-positive rate (FPR). RESULTS: The mean observed rank of 5.08 in the
      cases was significantly higher than the expected 3.18 (p-value = 0.013).
      Pregnancies that will develop a preeclampsia exhibit 2.39-fold higher levels of
      maternal plasma cell-free fetal DNA compared to matched controls. DR was 33 and
      50% at an FPR of 5 and 10% respectively. CONCLUSIONS: The estimated DR allows to
      consider fetal DNA as a potential variable to predict preeclampsia in a low-risk
      population. Further studies will be addressed to calculate a parametric
      statistical algorithm and to estimate a proper posterior risk of the disease by
      means of fetal DNA alone or combined with other markers.

PMID- 14974112
TI  - Pilot study on the midsecond trimester examination of fetal nasal bone in the
      Chinese population.
AB  - OBJECTIVES: Hypoplasia of the nasal bone of fetuses affected by trisomy 21 and
      other aneuploidies could be detected by prenatal ultrasound examination and was
      an important new marker in the detection of Down syndrome in the second
      trimester. Racial differences in fetal nasal bone length have been reported.
      However, there was no reference range for the fetal nasal bone length (NBL) in
      the Chinese population. We conducted a pilot study to investigate the
      reproducibility of the measurement of fetal NBL in the mid second trimester and
      to determine whether there is any difference in NBL between the Chinese and the
      Caucasian population. METHODS: From June 2002 to February 2003, 198 Chinese women
      were examined. Ultrasound measurements of NBL were performed on a strictly
      midsagittal plane in normal singleton fetuses at 15 to 23 weeks' gestation.
      RESULTS: The mean difference in the NBL between the two investigators was small
      (mean = 0.043 mm; 95% CI, -0.033 to 0.12), and there was substantial agreement
      between the measurements for each observer. Limits of agreement were -0.48 to
      0.35 and -0.29 to 0.22 mm in the two investigators respectively. It was found
      that the median length of the nasal bones increased from 3.5 mm at 15 weeks to
      6.7 mm at 23 weeks' gestation. There was a linear relationship between the length
      of the nasal bone and the gestational age. CONCLUSION: It was demonstrated that
      the measurement of nasal bone length was feasible and reproducible in the second
      trimester. The fetal nasal bone length in Chinese population appeared shorter
      than that of Caucasian and African-Americans. There is a need to establish a
      reference range of fetal NBL for the Chinese population.

PMID- 14974113
TI  - Ultrasound screening of fetal structural abnormalities at 12 to 14 weeks in Hong
      Kong.
AB  - OBJECTIVE: Ultrasound screening for fetal abnormalities is conventionally
      performed at 18 to 20 weeks of gestation. Recent data suggested that many fetal
      structural abnormalities could be detected by ultrasound examination at 12 to 14
      weeks of pregnancy. In this study, we investigated the effectiveness of early
      ultrasound examination in the detection of fetal abnormalities in women aged 35
      years or older. METHODS: From February 1998 to March 2001, pregnant women aged 35
      or above were examined by transabdominal and transvaginal sonography between 12
      and 14 weeks of gestation. If the anatomical survey was normal, the women
      underwent routine 16- to 20-week ultrasound examination. Pregnancy outcome was
      obtained from the hospital records or by contacting the subjects. RESULTS: Twenty
      six of the 1609 fetuses had structural abnormalities. Fourteen were detected at
      the ultrasound examination at 12 to 14 weeks. Detection rate was 53.8% (14/26;
      95% CI 44, 64) with a false-positive rate of 0.3% (5/1583; 95% CI 0.16, 0.44).
      Six additional abnormalities (23.1%, 6/26) were detected at 16- to 20-week
      ultrasound examination. The overall detection rate of structural abnormalities
      was 76.9% (20/26; 95% CI 68.6, 85.2). CONCLUSIONS: The effectiveness of
      ultrasound examination at 12 to 14 weeks to screen for fetal abnormalities
      approached that achieved at 20 weeks and can be a good adjunct to the
      conventional examination.

PMID- 14974114
TI  - Prenatal diagnosis of enteric duplication cyst of the tongue.
AB  - Cysts located on the tongue are rare and usually diagnosed in childhood. Here we
      report on the prenatal diagnosis of an unusual cystic malformation of the tongue
      with heterotopic intestinal tissue explored by prenatal ultrasound, magnetic
      resonance imaging and on its surgical treatment and histological examination. The
      prenatal differential diagnoses as well as perinatal management of cystic lesions
      of the tongue are reviewed.

PMID- 14974115
TI  - Structural chromosomal mosaicism and prenatal diagnosis.
AB  - True structural chromosomal mosaicism are rare events in prenatal cytogenetics
      practice and may lead to diagnostic and prognostic problems. Here is described
      the case of a fetus carrying an abnormal chromosome 15 made of a whole chromosome
      2p translocated on its short arm in 10% of the cells, in association with a
      normal cell line. The fetal karyotype was 46,XX,add(15)(p10).ish
      t(2;15)(p10;q10)(WCP2+)[3]/46,XX[27]. Pregnancy was terminated and fetus
      examination revealed a growth retardation associated with a dysmorphism including
      dolichocephaly, hypertelorism, high forehead, low-set ears with prominent
      anthelix and a small nose, which were characteristic of partial trisomy 2p.
      Possible aetiologies for prenatal mosaicism involving a chromosomal structural
      abnormality are discussed.

PMID- 14974116
TI  - Reversal of twin-twin transfusion syndrome: frequency, vascular anatomy,
      associated anomalies and outcome.
AB  - OBJECTIVE: To determine the frequency of reversal of transfusional gradient and
      phenotype in a large cohort of prospectively studied cases of twin-twin
      transfusion syndrome (TTTS) and seek evidence of clinical or placental
      anastomotic associations. METHODS: Consecutive cases of TTTS seen over an eight
      year period with serial documentation of ultrasonic growth, liquor volume and
      fetal and placental Doppler studies were reviewed. Postnatal injection studies
      were inspected. RESULTS: Reversal of TTTS occurred in 5 of 96 affected
      pregnancies (5%). Two of the five cases had underlying aneuploidy or genetic
      syndrome, higher than the 2% frequency found in cases without reversal of TTTS (p
      < 0.05). Placental anastomotic configurations provided no consistent explanation
      for reversal of phenotype. CONCLUSION: This study documents the frequency of
      reversal of the direction of TTTS, and suggests that it is a heterogeneous
      condition. Reversal of donor-recipient phenotype may be explained by haemodynamic
      changes secondary to underlying aneuploidy/genetic syndromes, to the presence of
      multiple anastomoses in either direction or following laser ablation. This series
      together with previous case reports argues for a high level of suspicion for
      underlying aneuploidy, genetic syndrome or structural defects where there is
      reversal of the donor-recipient phenotype.

PMID- 14974117
TI  - Retrospective diagnosis and subsequent prenatal diagnosis of Nijmegen breakage
      syndrome.
AB  - OBJECTIVE: We report on the retrospective diagnosis of Nijmegen breakage syndrome
      (NBS) confirmed by molecular genetic analysis and consecutive prenatal diagnosis
      in the same family. METHOD: Thirteen years after the death of their daughter due
      to fatal recurrent infections, a couple presented in our genetic counselling unit
      asking for the recurrence risk of their daughter's disease. Retrospective
      analysis of the medical record suggested that the girl might have suffered from
      NBS. Therefore, molecular genetic analysis for NBS was performed in the parents.
      RESULTS: After the diagnosis, NBS could be indirectly proven by molecular genetic
      heterozygosity testing of the parents, and a reliable prenatal diagnosis for a
      new pregnancy could be offered. In a following pregnancy, a massive hydrocephalus
      was diagnosed by ultrasound investigation. Amniocentesis was performed, and
      molecular analysis of the fetal DNA revealed homozygosity for the NBS1 mutation
      657del5. CONCLUSION: The analysis of this family allows a further delineation of
      the prenatal NBS phenotype including hydrocephalus and dystopic kidneys that are
      helpful parameters to recognise NBS prenatally, also by ultrasound investigations
      in pregnancy. Additionally, we conclude that hydrocephalus might be more common
      in NBS patients than previously suggested.

PMID- 14974118
TI  - The prenatal diagnosis of congenital disorders of glycosylation (CDG).

PMID- 14974119
TI  - ROC analysis of an erythroblast morphologic scoring system to improve
      identification of fetal cells in maternal blood.
AB  - OBJECTIVES: Nucleated red blood cells are used in research settings as a target
      cell type for investigations of noninvasive prenatal diagnosis, and these cells
      have a characteristic nuclear morphology and hemoglobin staining pattern that
      makes them distinguishable from maternal cells. Recently, we developed an
      erythroblast scoring system based on these characteristics. Here, we employ
      statistical analyses to further characterize the utility of this scoring system.
      METHODS: A total of 170 nucleated red blood cells isolated from peripheral blood
      of four women undergoing elective termination of a trisomy 21 male fetus were
      analyzed. Each of the four scoring system parameters, whose values range from 0
      to 3 points, served as an independent variable to determine its significance for
      the correct identification of a cell as fetal or maternal. A logistic regression
      was used as a multivariable statistical tool. RESULTS: Forty-four patterns of the
      four parameters were found in the overall series. Some patterns were exclusively
      associated with maternal cells (e.g. 1-1-1-1 and 1-1-2-2), and others were
      exclusively associated with fetal cells (e.g. 3-2-2-2 and 3-2-3-2). A detection
      rate of 73.9% at a false-positive rate of 5% resulted from a random simulation
      model performed with a 1:5 case:control matched set. The variables most
      predictive of a cell being fetal were gamma hemoglobin staining intensity of
      cytoplasm and nuclear roundness. CONCLUSIONS: The modified scoring system
      presented here improves upon the previously reported, unmodified erythroblast
      scoring system. These statistical analyses suggest that the scoring system is a
      promising method that aids in distinguishing fetal and maternal NRBCs for
      prenatal diagnostic applications and that it may be amenable to automated
      microscopy by applying the discrete morphological parameters as computational
      classifiers.

PMID- 14974120
TI  - Prenatal diagnosis of mos46,X,del(Y)(q11.2)/45,X by cytogenetic and molecular
      studies with multiplex STR analysis.
AB  - OBJECTIVES: To present the prenatal diagnosis of a fetus of
      mos46,X,del(Y)(q11.2)/45,X by cytogenetic and molecular analysis. CASE AND
      METHODS: A 35-year-old pregnant woman came to our hospital for amniocentesis, and
      fetal chromosomal aberrations with mos46,X, + mar/45,X were found. Fluorescence
      in situ hybridization revealed the existence of a Y centromere on the marker
      chromosome. Analysis with six pairs of short tandem repeat markers showed that
      the genomic DNA extracted from the uncultured amniotic fluid cells contained a
      deletion of Yq11.1-Yq11.2. Spermatogenesis loci of the Y chromosome were studied
      using four sets of multiplex PCR. The proximal two markers DYS271 and KALY were
      present and the other 16 distal markers were deleted. No deletion was noted in
      the Y chromosome of the father. RESULTS: Cytogenetic and molecular analyses
      revealed deletions of AZFb, d, and c regions on Yq11.2-Yqter in the fetal Y
      chromosome. Postmortem examination of the fetus showed a grossly normal male
      fetus with normal external genitalia and testes. CONCLUSION: The present report
      demonstrates that molecular analysis using polymorphic microsatellite markers and
      multiplex PCR is a useful complement to cytogenetic methods for the
      identification and the characterization of Y-chromosomal deletions.

PMID- 14974121
TI  - Integrated first- and second-trimester Down syndrome screening test among
      unaffected IVF pregnancies.
AB  - OBJECTIVE: The aim of the current study was to assess the profile of markers that
      constitute the integrated test and to measure its false-positive rates (FPR)
      among a preselected group of unaffected IVF pregnancies. These results were
      compared with the reference laboratory values that reflect the general obstetric
      population, which underwent the same investigative protocol. METHODS: Ninety-nine
      unaffected singletons from IVF-pregnant women and 1781 controls, all evaluated by
      the same laboratory, underwent a nondisclosure integrated Down syndrome screening
      test. This test comprised first-trimester nuchal translucency (NT) and pregnancy
      associated plasma protein-A (PAPP-A) assessment, followed by a midgestation
      quadruple test. Only upon completion of the integrated screening test, the
      parturient women were informed of its results. RESULTS: The mean maternal age of
      the study and the control group was 32.2 +/- 4 and 30.4 +/- 4 years respectively
      (t-test <0.005). The marker levels were expressed as multiples of the gestation
      specific normal medians. The IVF group had lower PAPP-A (0.78 vs 1.03, t-test P <
      0.05) and higher NT (1.14 vs 1.01, t-test P < 0.05) values, respectively. All the
      other markers were similar for both groups. On the basis of the integrated test,
      a higher rate of IVF pregnancies were defined as being screen-positive (6.1% vs
      3.7%), although the values did not reach a level of statistical significance.
      CONCLUSIONS: Since NT alone yielded the same FPR as the integrated test, the
      option of various sonographic screening combinations in this group warrants
      further investigation.

PMID- 14974122
TI  - Prenatal diagnosis of the distal 11q deletion and review of the literature.
AB  - OBJECTIVES: To present the prenatal diagnosis of de novo distal 11q deletions and
      a review of the literature. CLINICAL SUBJECTS AND METHODS: A 31-year-old
      primigravid woman underwent amniocentesis at 20 weeks' gestation because of a
      maternal serum alpha-fetoprotein (MSAFP) level of 2.63 multiples of the median.
      Amniocentesis demonstrated a karyotype of 46,XY,del(11)(q24.2). The parental
      karyotypes were normal. Level II ultrasound revealed short femurs and humeri, and
      overlapping of the toes. Postnatally, the proband manifested additional findings
      of the characteristic facial dysmorphism and camptodactyly. A 38-year-old gravida
      2, para 1, woman underwent amniocentesis at 18 weeks' gestation because of
      advanced maternal age. Amniocentesis revealed a karyotype of
      46,XX,del(11)(q24.1). The parental karyotypes were normal. Level II ultrasound
      did not show fetal structural abnormalities. Postnatally, the proband manifested
      characteristic facial dysmorphism and camptodactyly. RESULTS: Of these two cases,
      genetic marker analysis determined the paternally derived distal deletions of
      chromosome 11q and the deletion breakpoints. A comparison of the present cases
      with the reported cases of prenatally diagnosed distal 11q deletion is made.
      CONCLUSION: The distal 11q deletion can be identified prenatally because of
      parental balanced translocations involving chromosome 11, previous-term infants
      with an unbalanced rearrangement, advanced parental age, sonographically detected
      fetal abnormalities and abnormal maternal serum screening. Fetuses with de novo
      distal 11q deletions may be associated with elevated MSAFP and abnormal
      sonographic findings of the digits and limbs in the second trimester.

PMID- 14974123
TI  - Trisomy 13 mosaicism: study of serial cytogenetic changes in a case from early
      pregnancy to infancy.
AB  - We report a patient whose chorionic villus sampling showed a nonmosaic trisomy 13
      [46,XX,der(13;13)(q10;q10)]. Subsequent amniocentesis and cordocentesis showed
      varying percentages of abnormal cells (77 and 78% in two amniocentesis; 14% in
      cordocentesis) and mosaic trisomy 13 was impressed. Prenatal fetal ultrasound
      scanning revealed only mild structural abnormalities (echogenic cardiac foci,
      transient lemon head, transient skin oedema). The mother chose to continue the
      pregnancy. Karyotyping of the cord blood, peripheral blood, umbilical cord,
      urine, and chorion were performed postpartum. The process of correction appeared
      to exist in the placenta (indirect evidence from coexistence of trisomy 13
      [46,XX,der(13;13)(q10,q10)], euploidy [46,XX], aneuploidy [46,XX,-13, +mar], and
      monosomy 13 [45,XX,-13] in the chorion at birth). The baby had survived beyond
      eight months of age at the time of submission. Few structural abnormalities
      except low-set ears, absence of the 12th rib, and cardiomegaly with ventricular
      septal defect, were noted postnatally. The growth reached 95th percentile at the
      age of one month. Development milestones were not delayed at serial evaluations.
      Her ventricular septal defect was corrected surgically at the age of six months.
      Karyotypes of her skin fibroblasts, blood lymphocytes, and cardiac tissue were
      all normal [46,XX] at the time of surgery. Difficulties of the genetic counseling
      are also discussed.

PMID- 14974124
TI  - Megacystis in the first trimester.

PMID- 14974125
TI  - Nuchal translucency and gestational age.

PMID- 14974126
TI  - First-trimester increased nuchal translucency as a prenatal sign of Zellweger
      syndrome.

PMID- 14974127
TI  - Special issue: I.C. Gunsalus.

PMID- 14974128
TI  - Pet owners and risk factors in cardiovascular disease.

PMID- 14974129
TI  - [Cabbage leaf therapy of gonarthrosis. At first I smiled about white cabbage,
      then I tried it].

PMID- 14974130
TI  - Magnetism and the brain.

PMID- 14974133
TI  - Sharks in the soup.

PMID- 14974132
TI  - 'Smart dust' is way cool.

PMID- 14974131
TI  - Wired by words.

PMID- 14974134
TI  - Medicare bill expected to benefit PTs.

PMID- 14974135
TI  - Back to school.

PMID- 14974136
TI  - Therapeutic light.

PMID- 14974137
TI  - Purchasing prowess.

PMID- 14974138
TI  - Universal challenges.

PMID- 14974139
TI  - Getting up goals.

PMID- 14974140
TI  - Freestyle seating.

PMID- 14974141
TI  - The power cycle.

PMID- 14974142
TI  - Private practice premonitions, the sequel.

PMID- 14974143
TI  - Good news from the Hill.

PMID- 14974144
TI  - Employer options. The new Medicare Prescription Drug Act will have a big impact
      on employers and their health insurance plans.

PMID- 14974145
TI  - [Biofilms in infectious diseases].
AB  - Microorganisms attack and grow upon living as well inorganic surfaces, forming a
      "biofilm". Biofilms are a serious problem of public health, because biofilm
      associated microorganisms exhibit increased resistance to antibiotics. The
      mechanisms of biofilm formation, the mechanisms of resistance and the
      possibilities of therapy are briefly summarized.

PMID- 14974146
TI  - [Telemedicine system for remote medical consultation. Internal medicine patients
      cared for in Italy from Angola].
AB  - Thirty-five patients, living in Italy and bearing chronicle internal diseases,
      have been followed by a senior specialist, displaced to Angola for three months.
      The senior specialist was assisted by a junior physician, who was in touch with
      the patients in Italy. Both of them were provided with a network equipped
      portable personal computer. Five patients dropped-out. At least 4 of them were
      brought about by the method. Despite the senior specialist has always fed back
      the junior physician within 48 hours as a maximum, in 8 patients the time was too
      long to challenge acute complications of the diseases, requiring urgent decisions
      or consultations by extra-expertise. The transmission of X-ray, ultrasound and
      radionuclide scan pictures was satisfactory. The rapid development of both
      hardware and software and the high technology network like ISDN will enable to
      overcome most of the problems and keep the patient and the doctor in a narrow
      contact. But project inputting telematic and informatic systems into the
      developing countries are expectedly to be poorly sustainable.

PMID- 14974147
TI  - [Stress, job satisfaction, and quality of life in the health professions: the
      role of burn-out and personality features].
AB  - Emotional exhaustion, depersonalisation and personal achievement represent the
      main dimensions of the "burn-out syndrome" (B.O.). The risk of B.O. is especially
      elevated among people working in helping professions. These professionals work in
      settings that are characterised by a very strong emotional involvement. The
      representative sample of this study consisted of 100 subjects of whom a part of
      them worked in a psychiatric setting and others who didn't. All of them have been
      assessed through the M.B.I. and the E.P.Q. The purpose of the present study was
      especially: 1) to explore the existence of B.O. and its level, and 2) to verify
      the existence of some personality characteristics of employees which could be
      considered as possible predictors of B.O. syndrome. The statistical analysis
      showed that the three B.O. dimensions and therefore the B.O. syndrome were within
      the group of persons working in helping professions. The outcomes of this study
      encouraged an intervention focused on three parts: job organisation, self
      management of psychological well-being and teamwork effectiveness.

PMID- 14974148
TI  - [Non-invasive hemodynamic assessment with bioimpedance in patients with
      subclinical hypothyroidism before and after treatment with levo-thyroxin].
AB  - Subclinical hypothyroidism is characterized by normal serum levels of free
      thyroxine and triiodothyronine with increased serum levels of thyroid-stimulating
      hormone (TSH) without symptoms. We evaluated by thoracic electrical bioimpedance
      cardiography the hemodynamic pattern of 38 patients with subclinical
      hypothyroidism, before and after 6-month therapy with levo(L)-thyroxine. We have
      not evidenced statistically significant differences for cardiac index, cardiac
      frequency and vascular peripheral resistances. TSH levels were decreased in a
      statistically significant way. Results obtained in our study show that
      hemodynamic pattern is not changed after hormone therapy in patients affected by
      subclinical hypothyroidism.

PMID- 14974149
TI  - [Non-tubercular and non-brucellar spondylodiscitis: preliminary clinico
      microbiologic analysis of 37 cases].
AB  - Disk-space infection caused by organisms other than Mycobacterium tuberculosis or
      Brucella species seems to be an emerging disease due to an increase of the
      population at risk. However, few data are presently available from Italian
      institutions. In this article we report our "tot" month prospective experience on
      etiology and clinical presentation of disk-space infections in relation to their
      community (COM) or nosocomial (postoperative [POS] or non-postoperative [NPOS])
      acquisition. Major results were: 1) a different microbial distribution among
      etiologies of COM, NPOS and POS infections; 2) more frequent distance infection
      as predisponing factor among NPOS infection than among COM and NPOS ones; 3)
      absence of fever and more frequent radicular extension of pain among POS
      infections. Due to the numerous potential microbial etiologies, culture of TC
      guided-disk aspirated material is of paramount importance for pathogen-targeted
      antimicrobial therapy.

PMID- 14974150
TI  - [Treatment of HIV infection in clinical practice. Wide-range genotypic resistance
      to all nucleoside analogues and protease inhibitors, and severe intolerance to
      all non-nucleoside inhibitors of inverse transcriptase].

PMID- 14974151
TI  - [The devil and the patient].

PMID- 14974152
TI  - ["Understanding cancer": a passionate message from Antonio Tabucchi to the
      physicians].

PMID- 14974153
TI  - [Complications following radical hysterectomy for cervical carcinoma].
AB  - Reporting and scoring treatment complications in gynecological cancers is
      difficult because of the variety of normal tissues, anatomical structures and
      treatment disciplines involved, making it impossible to compare series of
      patients treated in different institutions even with the same strategy. An
      international group of experts developed a multidisciplinary database to
      identify, score and report early and late normal tissue damage regardless of
      treatment strategy. The Franco-Italian Glossary provides clinicians with a
      comprehensive tool for scoring and describing complications regardless of the
      type of treatment delivered. The widespread use of this Glossary should at last
      allow objective comparisons on the nature and intensity of complications in
      patients treated in different Centers and/or with different strategies. The
      urinary tract is confirmed as the dominant site of complications after radical
      surgery with or without radiotherapy. Among the urological complications, the
      changes in bladder capacity and compliance appear as one of the major problems
      for the patients. The attempt to tailor the radicality according to tumour and
      patients characteristics seems to be one of the strategies to reduce the
      incidence of complications and their severity after surgical treatment of
      cervical cancer. The association of radiotherapy with radical surgery is
      generally recognized as an important risk factor in the determination of organ
      complications through vascular and fibrotic damage.

PMID- 14974154
TI  - [Neuroendocrine features of prostatic tumors: state of the art].
AB  - Neuroendocrine (NE) differentiation in prostate cancer has received much
      attention recently because it has been found to be associated with androgen
      independence and shortened patient survival in some studies. The present review
      focuses on morphogenics origins of NE cells, growth properties and the androgen
      receptor status and relationship between NE-secreted products and regulation of
      angiogenesis and apoptosis.

PMID- 14974155
TI  - [Churg-Strauss syndrome].
AB  - Churg-Strauss syndrome (CSS) is a rare systemic vasculitis occurring in patients
      with a history of asthma or allergy and eosinophilia. Although lungs, skin, and
      peripheral nervous system are the most common sites of involvement, many other
      organs, including heart, kidneys, and gastrointestinal tract, can be affected.
      CSS is an eosinophil-mediated disease, but its pathophysiology is not fully
      known. There are no specific laboratory tests for CSS. The main laboratory
      characteristics are peripheral blood eosinophilia, elevated serum IgE levels, and
      the presence of an inflammatory syndrome. Antineutrophil cytoplasmic antibodies
      directed against myeloperoxidase are positive in approximately one-half of
      patients. The diagnosis of CSS rests on the association of the clinical features
      of the disease with its histologic hallmarks. The biopsy of affected tissues may
      show a spectrum of histologic changes, including leukocytoclastic or necrotizing
      vasculitis, eosinophilic tissue infiltration, vascular and extravascular
      granulomas. The involved vessels are small arteries, veins, arterioles, venules,
      and capillaries. Corticosteroids, sometimes in combination with a cytotoxic
      agent, such as cyclophosphamide, are the most effective treatment of CSS.
      Intravenous immunoglobulins or interferon-alpha may be useful for patients
      refractory to conventional treatment.

PMID- 14974156
TI  - [Effect of learning about the human genome on the development of pathology].
AB  - On the basis of data of the Human Genome Project, it was embraced the newest
      information about the gene content of the human genome, the disease genes, the
      parasitic DNA, the single nucleotide polymorphisms, the repeat sequences, the
      cytoskeletons, the regulation of cell proliferation, and their medical
      consequences. The applicability of the acquaintance with the human genome in
      pathology is presented with a few examples of our own. The significance of the
      single nucleotide polymorphisms in susceptibility to, or protection from, a host
      of disease is illustrated by the example of the allele variation of Apo-E gene.
      The copy number of the N-myc gene in neuroblastomas and HER2/neu gene in breast
      carcinomas was determined with quantitative PCR techniques. The monoclonally
      increased abnormal p53 protein expression was found in small cell lung cancer (in
      90% frequency), in oro-pharyngeal carcinomas (82%), in esophageal squamous cell
      carcinomas (59%) in stomach cancer (33%), in colon carcinomas (27%) and in soft
      tissue sarcomas (13%). These data advert to the fact that the mutation of the p53
      gene is much more frequent in those tumors in which the basic tissue is directly
      exposed to with the environmental carcinogens. It is now known, that near the
      repetitive sequences, gene rearrangement can more easily be evolve. Finally, we
      have determined the conditions of the accomplishment of the molecular
      pathological diagnosis: (1) It is applicable, when the classic morphology does
      not eventuate a conclusive result. (2) Well known and validated gene alterations
      are admissible to diagnostic purpose. (3) Only standard methods are applicable
      along with positive and negative controls. (4) The result has to correlate with
      the morphological picture, the immunohistochemical profile and the clinical data.
      (5) It is necessary to be able to appropriately interpret the molecular
      biological result, which is then incorporated in the pathological report. (6) The
      ethical, legal and social consequences must be considered.

PMID- 14974157
TI  - [ATP7B gene mutations in Hungarian patients with Wilson disease--case reports to
      illustrate the diverse clinical presentations].
AB  - ATP7B gene mutations were examined in 70 Wilson patients from Hungary. 11
      different mutations were found. In Hungary, similarly to other Central-Eastern
      European countries, the H1069Q was the most the frequent mutation, detected in 51
      patients (73%) by semi-nested polymerase chain reaction (PCR) based restriction
      fragment length polymorphism (RFLP) assay. 10 further mutations have been found
      by sequencing as follows: P767P-fs, R778G, K844K-fs, I857T, R969Q, T977M, E1064K,
      M769L, Y715H and P1273S. These latter three mutations have not been described
      before. Among the 11 mutations there are five, which have been published only in
      patients of Turkish, Italian or Albanian origin. It might be the genetic
      consequence of the 150 years long occupation of Hungary in the 16th and 17th
      century by Turks. The genotype-phenotype analysis showed that the Kayser
      Fleischer ring was more frequent (10/12 = 83%), and the age at the diagnosis was
      higher in H1069Q homozygous patients than in compound heterozygous or negative
      patients. Diverse clinical presentation of the disease was demonstrated by case
      reports giving messages for the practitioners. The gene mutation analysis is of
      particular importance in siblings of the index patient, since the detection of
      two mutant allels confirm the diagnosis of the disease even in absence of
      symptoms. The clinical manifestation of the disease can be preceded by the
      treatment.

PMID- 14974158
TI  - [Exhaled breath condensate and its analysis--a new method in pulmonology].
AB  - In the middle of the nineties a new, non-invasive method for investigation of the
      lung aroused the interest of many researchers: the exhaled breath condensate. It
      shows the extent of the interest that in the last five years more than 80
      original articles have been published in this theme. Many substances are found in
      the expired breath which are detectable in the liquid that we obtain by cooling
      (= condensing) the exhaled breath. The advantages of this method are that it is
      non-invasive, convenient, it could be performed with mechanically ventilated
      patients as well as with children. The most studied substance is the hydrogen
      peroxide, which is the marker of oxidative stress, and its level in condensate is
      elevated in numerous inflammatory diseases. 8-isoprostane was also studied a lot,
      which is another marker of oxidative stress. Numerous substances could be even
      measured in condensate, so the decay-product of nitric-oxide (nitrite, nitrate,
      nitrotyrosine), further nitrosothiol, adenosine, ammonia, different ions,
      leukotrienes, cytokines; recently even other feature of condensate is examined,
      such as its pH. The different mediators could help us to know better the
      diseases, support the diagnosis, follow the treatment or the disease. In this
      study the authors attempt to present the most important knowledge till now.

PMID- 14974159
TI  - [Lingual thyroid].
AB  - Lingual thyroid is a rare embryological aberration with incidence of 1:100,000.
      It is an ectopic thyroid tissue. In most cases, it is diagnosed in childhood and
      young adulthood but frequently around menopause. It appears as a mass on the base
      of the tongue causing mostly local symptoms often with hypothyroidism, rarely
      with thrive and mental retardation. Authors describe the features, diagnosis and
      therapy of lingual thyroid with the case of a 23-year-old woman. They analyze the
      probable pathomechanism and potential risk of malignant transformation of lingual
      thyroid. In this case, the diagnosis was described at the age of 17, but therapy
      or further investigation did not take place then. Six years later the patient
      visited our surgery with local complaints in euthyroid phase. Since the
      suppression therapy proved to be unsuccessful, the problem was finally solved by
      operation.

PMID- 14974160
TI  - [Chronic recurrent multifocal osteomyelitis].
AB  - The chronic recurrent multifocal osteomyelitis has been reported very rarely in
      the literature. However, its significance must be emphasized, because it is a
      spontaneously healing, benign disease, as compared to the classical forms of
      osteomyelitis. It leaves behind almost no residual symptoms, and many operations,
      long antimicrobial therapy may be avoided by diagnosing it. In this case report
      the authors provide the review of the disease through the history of a 9-year-old
      boy.

PMID- 14974161
TI  - [Long-term pharmacotherapy of epilepsy].

PMID- 14974162
TI  - A scientific journal.

PMID- 14974163
TI  - Orthodontic case report--the Rowland Award.

PMID- 14974164
TI  - Almost 200,000 children with disabilities in Texas.

PMID- 14974165
TI  - Why not gold? Contemporary esthetics and restorative practice.
AB  - In today's dental world, there are many more options of materials and equipment
      than there was years ago. It can be very confusing for anyone to sift through the
      marketing and lectures and determine which of the new materials are best suited
      for our patients. Classic gold techniques have been around for over 100 years and
      have an obvious track record. Leinfelder (7) has stated, "Gold alloys are
      certainly the best materials by far in terms of maintaining a functional
      occlusion and longevity." Underutilized in the recent past, gold is undergoing a
      comeback in many areas. A major dental company recently introduced a new casting
      gold and recent advertisements for gold-related products have reappeared in
      dental magazines. It is incumbent upon the modern dental professional to be aware
      of all the restorative options available, learn how to perform them, and then
      choose the technique that will be the most appropriate for each situation.
      Longevity should always be a factor in the decision making process and gold is
      the answer in many applications.

PMID- 14974166
TI  - "I'm sure it is all right (swallowed/aspirated casting?)" Response to ethical
      dilemma #45.

PMID- 14974167
TI  - Oral and maxillofacial pathology case of the month. Cicatricial pemphigoid
      (mucous membrane pemphigoid).

PMID- 14974168
TI  - Structure of peripheral cementum of normal equine cheek teeth.
AB  - The structure of peripheral cementum of mandibular and maxillary cheek teeth was
      studied by gross observation, light microscopy, and scanning and transmission
      electron microscopy. Teeth from four horses aged 4, 8, 17, and 30-years-old were
      examined. The cementum of the occlusal surface was thicker on the buccal aspect
      when compared with the lingual aspect of mandibular teeth. The cementum of the
      occlusal surface was thicker on the palatal aspect when compared with the buccal
      aspect of maxillary teeth. There was no peripheral cementum on the interdental
      aspects of either mandibular or maxillary cheek teeth. In the adult tooth,
      cementum covered the crown and root surfaces. The peripheral cementum of the
      gingival region showed a dramatic increase in thickness compared with cementum
      covering the alveolar portion of the embedded tooth. At a microscopic level,
      three layers (primary, secondary, and tertiary) were identified within cementum.
      The increase in cementum in the gingival region was of tertiary cementum. All
      three layers contained vital cementocytes. There was a well-developed vascular
      system within the cementum. Nerve bundles were also present. Three cementoblast
      profiles were identified at the junction of the cementum with the periodontal
      ligament. The results reported in this paper show that cementum is a dynamic
      vital tissue. These findings should contribute to a greater understanding of the
      etiology and pathogenesis of cemental caries and periodontal disease in the
      horse.

PMID- 14974169
TI  - Surgical extraction of a fractured, non-vital deciduous tooth in a tiger.
AB  - A 10-month-old, female/intact tiger (Panthra tigris) was presented for a
      fractured deciduous mandibular right canine tooth, mandibular swelling, and a
      cutaneous draining tract ventral to the apex of the fractured tooth. The tooth
      had chronic pulpal exposure and was considered non-vital with periapical
      osteomyelitis. This case report describes treatment to optimize normal
      development and eruption of the permanent mandibular right canine tooth.

PMID- 14974170
TI  - Radicular cyst of the premaxilla in a dog.
AB  - A 13-year-old, male/neutered Border Collie dog was diagnosed with a radicular
      cyst of the left premaxilla. Tooth extraction and curettage of the lesion
      resulted in a positive clinical outcome 6-months following treatment.

PMID- 14974171
TI  - Trismus secondary to squamous cell carcinoma in a cat.

PMID- 14974172
TI  - Line angle incisions.

PMID- 14974173
TI  - Mandibular incisor apically repositioned flap in the dog.

PMID- 14974174
TI  - [Analysis of depression among persons with middle and moderate asthma].
AB  - The aim of the study was to establish a difference/lack of difference in
      depression level between 83 patients with moderate or middle asthma and 78
      healthy persons. Investigated group consisted of 37 men (aged 35.2 years) and 46
      woman (38.5 years), and control group accordingly of 37 men (35.6 years) and 41
      women (35.2 years). Results of Beck Depression Inventory appeared in asthmatic
      group 41% persons without depression symptoms and 18%--with severe depression
      level (in comparison to healthy persons 78.2% and 3.8%). Difference was
      statistically significant (p < 0.000).

PMID- 14974175
TI  - [Depression and perceived general control, effort and reward at work, in men and
      women at age 45-64, residents of Cracow].
AB  - The aim of the study was to assess the relation between depression: effort and
      reward at work, perceived general control, control over life and over health. The
      studied sample were 3544 men and women aged 45-64 years, residents of Cracow.
      After adjustment for age, education, marital status, smoking and physical
      activity the increase of the effort coefficient by 1 standard deviation was
      related with an increase in the risk of depression by 31% in men and 43% in
      women. Increase of the reward coefficient by 1 standard deviation was related to
      a decline in the risk of depression by 31% in men and 36% in women. Increase of
      the perceived general control coefficient by 1 standard deviation was related
      with a decrease in the risk of depression by 55% in men and 51% in women and
      increase in the perceived life control coefficient by 1 standard deviation was
      related to a decline in the risk of depression by 62% in men and 52% in women.
      Increase of the health control coefficient by 1 standard deviation was related
      with a decrease in the risk of depression by 17% in women only. Effort and reward
      at work, perceived general control and control over life was related to
      depression in men and women. Perceived control over health was related to
      depression in women but not in men.

PMID- 14974176
TI  - [Assessment of nutritional status of prepubertal students in Southeast Poland].
AB  - The aim of the investigation was to estimate the prevalence of malnutrition,
      overweight and obesity in prepubertal schoolchildren from Southeast Poland and to
      obtain information on obesity risk factors in children. A representative national
      sample of 480 school children (252 girls and 228 boys) between 8-9 years old was
      selected from 23 schools from Southeast Poland. Examinations included
      anthropometric measurements (weight and height) and questionnaires covering
      familial, socioeconomic and psychosocial factors. Body mass index (BMI) was
      calculated and used as an indicator of overweight. As a statistical method a
      cross-sectional, three-stage, probability-proportionate-to-size cluster sampling
      method was used. The prevalence of malnutrition was: 8%, the prevalence of
      overweight: 6.7% and of obesity 1.9%. A statistical significance between
      parenteral obesity and obesity of their offspring was found. The mothers obesity
      represented a higher risk of the condition for girls (p = 0.001), and obesity in
      fathers represented a higher risk for boys (p = 0.016) than girls. We found the
      association between obesity in children and physical activity (odds ratio: 2.55;
      95% CI: 1.12 5.8). A greater number of obese children skip breakfast as compared
      with other children (p = 0.058).

PMID- 14974178
TI  - The advantage of transverse laparotomy closed with continuous absorbable single
      layer stitch.
AB  - The authors emphasize the advantage of transverse incisions because they provide
      the surgeon not only with excellent bilateral view of the operated area, but what
      is most important, they have significantly least negative effect on respiratory
      functions and the composition of blood gases, which are of major importance in
      patients with chronic respiratory failure. Due to the much smaller retraction
      forces, the incidence of postoperative dehiscences and hernias is smaller. It is
      an incision which interferes the least with the innervation of the abdominal wall
      and thus is not only less painful, but has also better healing parameters, offers
      excellent access to pathology from oesophagus up to sigmoid. It is an ideal
      incision for left open abdomen due to much less retraction of the abdominal wall
      and described closure is safe, simple, cheap, fast and reliable in risk, obese
      patients with impaired healing. The closure by a continuous, absorbable, looped
      double suture is not only simple, but what is most important, it is reliable and
      associated with minimal postoperative complications. The mean time of closure
      13.6 min., supuration after 10th post-op day in 2%, none burst abdomen, 4
      incisional hernias (0.8%), these are significantly better results than compared
      to longitudinal incisions. Authors in details describe the running Smead Jones
      closure technique.

PMID- 14974177
TI  - [Thyroid peroxidase antibodies and thyroid diseases in children and adolescents
      with type 1 diabetes mellitus from Southeast Poland].
AB  - The authors evaluated the prevalence of TPO Ab and thyroid disorders in 219
      children and adolescents (119/54% girls) with type 1 diabetes from southeast
      Poland aged 3.2-22.3 years (mean age-13.7 +/- 3.9 years). Their age upon
      diagnosis ranged from 1.6 to 17.2 years (mean age--8.1 +/- 3.6 years), while
      diabetes duration was between 1 and 18.7 years (mean, 6.4 +/- 3.7 years). In
      addition to clinical assessment of all patients, determinations were made of
      serum TPO Ab, FT4 and TSH; thyroid ultrasound was performed in each patient with
      abnormal thyroid morphology and/or positive TPO Ab titer. Positive TPO Ab titer
      was demonstrated in 76 (34.7%) patients with type 1 diabetes; in this group 49
      showed no other overt thyroid pathological symptoms. Hashimoto's disease was
      detected in 26 children, Graves's disease in 1 girl. Twenty children (9.1%) with
      negative TPO Ab titter were shown to have euthyrotic goiter. Thus, thyroid
      abnormalities were demonstrated in 43.8% of the patients and were seen twice as
      often in girls than in boys (+ n = 69 > n = 27). Thyroid dysfunction was detected
      in 11 (5.05%) patients. These 11 patients with thyroid dysfunction constituted
      14.5% of the entire group of children with both type 1 diabetes and positive TPO
      Ab titer (n = 76). Ten patients were hypothyroid (including 8 with previously
      undiagnosed disease) and 1 girls had hyperthyroidism. The present results
      indicate that in each child with type 1 diabetes--apart from diabetes control-
      thyreologic assessment should be done, and the frequency and type of examinations
      should depend on the comprehensive preliminary evaluation.

PMID- 14974179
TI  - [Glimepiride in daily practice].
AB  - Application of the strategies and principles of oral diabetic therapy in type 2
      diabetes should be individualized based on the degree of hyperglycemia, insulin
      deficiency and insulin resistance. This paper presents the evaluation of the new
      third-generation sulfonylurea compound, glimepiride in daily practice.
      Glimepiride appears to have several clinical advantages over conventional
      sulfonylureas: different binding kinetics, advisable cardiovascular effects and
      beneficial extrapancreatic activity. This may explain the observation that
      glimepiride provides more stable blood glucose control and lower risk of
      hypoglycemia over some second-generation sulfonylureas. Glimepiride is safe and
      well tolerated in patients with type 2 diabetes. Finally, glimepiride also has
      been shown to be safe and effective in combination with other oral agents or with
      insulin treatment.

PMID- 14974180
TI  - [The modern view on the role of inflammatory factors in chronic heart failure and
      possibilities of pharmacological modification].
AB  - Chronic heart failure (CHF) is the state of reciprocal influences of
      neurohormonal factors and inflammatory markers. Many years of research and
      observations proved a particular meaning of cytokines and acute phase proteins in
      the pathophysiology of CHF. These markers are responsible for the repairing
      processes. There is a correlation between the activity of inflammatory factors,
      their plasma concentrations and clinical state of the patient. Basing on the
      cytokine's concentrations, the level of C-Reactive Protein (CRP) in the patient's
      blood and their changes in time we can predict the progression of the disease.
      Known medical references emphasise the fact that the pharmacological modification
      of inflammatory markers (interleukins, TNF-alfa, CRP) can have significant
      clinical consequences and in some cases can even cause regression of pathological
      symptoms. CRP plays an important role in the development and progression CHF and
      can be the clinical predictor not only in the cases of coronary disease but also
      can be useful in the group of patients with CHF. The introduction of drugs
      influencing CRP, interleukins and TNF-alfa levels to CHF therapy can be an
      effective solution called 'a golden therapy' improving clinical state and quality
      of patient's life.

PMID- 14974181
TI  - [Calcimimmetic and calcilytics: new perspectives of correction of abnormal
      parathormone (PTH) secretion].
AB  - Treatment of excessive secretion of parathyroid hormone (PTH) in primary
      hyperparathyroidism (I degree HPT) as well as in secondary hyperparathyroidism
      (II degree HPT) in chronic renal insufficiency is symptomatic, short-term acting
      and far from expectations. Recognition of properties of calcium receptor (CaR)
      expressed on parathyroid principal cell membranes created possibilities to
      explore new compounds that could alter directly PTH secretion and provide a novel
      therapy for direct correction of increased secretion of the hormone in these
      disorders. Ligands that activate this receptor and inhibit PTH secretion are
      called calcimimetics. Recently clinical trials with NPS R-568, a calcimimetic of
      the Ist generation, and AMG 073, a representative of calcimimetics of IInd
      generation, were completed. Calcimimetics, taken orally, effectively lower
      increased secretion of PTH and hypercalcemia in I degree HPT, by "pharmacologic
      parathyroidectomy". Such compounds are also safe and effective in dialysed
      patients with II degree HPT in chronic renal insufficiency: they decrease PTH
      plasma level and prevent parathyroid cell hyperplasia. The other compounds,
      called calcilytics and represented by NPS 2143, inhibit CaR resulting therefore
      in increase of PTH secretion. Administration of calcilytics would provide a
      valuable alternative to inhibit progression of osteoporosis. Subcutaneous,
      pulsative low doses of recombinant PTH (ALX1-11) administration induces increase
      of bone formation. Such an effect to some extent was obtained by transient
      increase of endogenous PTH secretion induced by oral administration of calcilytic
      NPS 2143 to osteopenic ovariectomized rats, especially if it was accompanied by
      supplementation of estrogens.

PMID- 14974182
TI  - [Hepatocyte growth factor: from diagnosis to clinical application].
AB  - Hepatocyte growth factor (HGF), initially identified and molecularly cloned as
      potent mitogen of primary cultured hepatocytes, has multiple activities in a
      variety of tissues during the course of development and also in various disease
      states. HGF plays key roles in the attenuation of disease progression as an
      intrinsic repair factor. It is also evident that HGF levels are regulated under
      different conditions, for example, during the course of pregnancy, aging, and
      disease. This review focuses on the levels of HGF in normal and
      pathophysiological situations and examines the relationships between HGF levels
      and disease, disease stage, and disease prognosis. The clinical potential of HGF
      as a treatment for subjects with various diseases is also given attention.

PMID- 14974183
TI  - [Carbonyl stress significance in the pathogenesis of dialysis-related
      amyloidosis].
AB  - Advanced glycation end products play a causal role in the pathogenesis of
      diabetic complications. Increased concentration of advanced glycation and
      lipooxidation end products in uremia are independent of hyperglycemia and
      decreased glomerular filtration rate. Increased carbonyl stress in chronic renal
      failure leads to nonenzymatic protein modification. Beta-2-microglobulin modified
      with carbonyl stress induces cell reaction, which may initiate dialysis
      arthropathy.

PMID- 14974184
TI  - [Primary hyperaldosteronism: report of two cases (normalization of hypertension
      after adrenalectomy)].
AB  - Two cases of Conn Syndrome with high hypertension, who were successful operated,
      have been prescribed. Retrospective evaluation of both cases suggests that severe
      and hypocalemic hypertension should motivate the researchers towards primary
      hyperaldosteronism. Etiology of the disease remains to be an important diagnostic
      challenge, optimal treatment will vary for each case of primary
      hyperaldosteronism. For individuals with aldosterone producing tumours the
      recommended type of treatment will be surgical as in most cases; it results in
      stabile normalization of RR level and abatement of metabolic dysfunction.

PMID- 14974185
TI  - [Otorhinolaryngological achievements of the 19th century Polish provincial
      physicians].
AB  - The history of the country town Sterdyn an administrative district of Siedlce is
      presented briefly. History of the hospital at this country town is described in
      more detail. The life, scientific, professional and organizational achievements
      of Sebastian Rosicki are presented (1830-1877), a distinquished Polish provincial
      physician. The Rosicki's successors at Sterdyn: Alojzy Podolski, Jozef
      Tchorznicki and Adam Jarosinski and their achievements are also depicted. Rosicki
      described a new method of medical examination of the posterior wall of the
      larynx, resembling the Gustav Killian method from 1891. The hospital reports from
      Sterdyn hospital in the "Tygodnik Lekarski" ("Weekly Medical") are a source of
      interesting information concerning XIX-th century Polish medicine. Rosicki used
      many interesting rhinolaryngological instruments, he treated many
      otolaryngological diseases.

PMID- 14974186
TI  - Newly enacted legislation addresses proper disposal of elemental mercury.

PMID- 14974187
TI  - Prompt payment.

PMID- 14974188
TI  - Orthodontic and cosmetic dental masking of avulsed maxillary central incisors.
AB  - Maxillary central incisors were avulsed and fractured to the extent that they
      were nonrestorable and unable to be reimplanted. Orthodontic treatment was
      advised to center and advance the lateral incisors so they could be cosmetically
      enlarged to replace the central incisors.

PMID- 14974189
TI  - Growing population diversity challenges New York State dentists.
AB  - Minority populations are becoming an increasingly larger component of the general
      population. A review of 2000 Census demographic-related data for the increasing
      number of minority children in New York State presents concerns regarding
      parental household living arrangements, family income, neighborhood
      characteristics, parental employment, education and disability rates. As minority
      populations increase in size, their children may well become the mainstay of
      dental practices, from now into adulthood. The challenge will be for
      practitioners to recognize these (and many related) factors as they develop
      programs to provide needed oral health services.

PMID- 14974190
TI  - Mediastinitis secondary to an odontogenic infection. A case report.
AB  - Infectious mediastinitis of odontogenic etiology is a rare occurrence in the
      United States. The mortality associated with descending necrotizing mediastinitis
      is estimated at 40% to 50%, even with advances made in management of such serious
      infections. The early diagnosis and aggressive treatment of odontogenic
      infections has made this entity relatively obsolete, but we have not been able to
      eliminate the disease process altogether. We report on a case that was managed
      successfully, albeit with a long, protracted course.

PMID- 14974191
TI  - Don't 'just do it' anymore.

PMID- 14974192
TI  - Gays and the seminary.

PMID- 14974193
TI  - Are body scans a scam?

PMID- 14974194
TI  - Aspirin: the oldest new wonder drug.

PMID- 14974195
TI  - Confessions of a fallen priest.

PMID- 14974196
TI  - Inner peace, good eats!

PMID- 14974197
TI  - How cities make their own weather.

PMID- 14974198
TI  - Stem cells in limbo.

PMID- 14974199
TI  - First-aid myths. Quick! You've just cut your finger. Are you sure you know what
      to do?

PMID- 14974200
TI  - Fat foods: back in court.

PMID- 14974201
TI  - Busted! Drug dealers are planting pot farms all over our national parks.

PMID- 14974202
TI  - Just say Om.

PMID- 14974203
TI  - Nuts (and fiber) to high cholesterol. Who needs statin drugs when you've got the
      grocery store?

PMID- 14974204
TI  - The new science of dyslexia.

PMID- 14974205
TI  - Too old to drive? How to tell when a senior is a danger--and how to take away the
      car keys.

PMID- 14974206
TI  - [Evidence Based Medicine (EBM)- an ideal solution or a fashionable ideology?].

PMID- 14974207
TI  - [Epidemiological aspects and methodological difficulties in establishing the
      causal relationship of Chernobyl nuclear accident with cancer].
AB  - The epidemiological, etiologic and clinical polymorphism of the morbid states,
      those accounted by radioactivity included, create major obstacles in the
      standardization of the methods for assessing the incidence of some diseases and
      their lethality. The many risk factors that can associate to radiations from
      various sources make the epidemiological data difficult to evaluate. The
      Chernobyl nuclear accident has revived the concerns and research in the field of
      prevention, early diagnosis and intervention of the effects of nuclear radiations
      by development of comparative, spatial and temporal, researches based on
      standardized methods, thus comparable results being provided. In Romania, the
      multidisciplinary epidemiological researches on the effects of Chernobyl accident
      upon health are still limited, and consequently insignificant for global
      conclusions.

PMID- 14974208
TI  - [Cytosolic calcium dynamics and smooth muscle contraction(II): Reticular calcium
      fluxes].
AB  - The contractile status of smooth muscle depends upon cytosolic Ca2+, the Ca(2+)
      sensitivity of actin-myosin interaction and various calcium-independent
      mechanisms. This second part of our overview is devoted to the complex
      involvement of endoplasmic reticulum in the cytosolic Ca2+ signals related to
      smooth muscle contractile activity, with a focus on the functional structure of
      reticular membrane proteins that ensure the respective Ca2+ fluxes. Ca2+ release
      is activated by cytosolic Ca2+, involving reticular channels called inositol
      triphosphate receptors and ryanodine receptors. Beside calcium and inositol
      triphosphate, cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate
      have recently emerged as intracellular signals that activate Ca2+ release. The
      reticular Ca2+ pump is essential both for the control of cytosolic Ca2+ and for
      the preservation of reticular stores.

PMID- 14974209
TI  - [Apoptosis--basic regulatory mechanism of bone remodeling].
AB  - Bone remodeling and regeneration take place permanently and are the result of a
      perfect balance between osteoclastic bone resorption and osteoblastic bone
      synthesis performed in the bone multicellular unit. Osteoblasts and osteoclasts
      differentiate from precursors under the influence of cytokines, growth factors
      mand cellular interactions controlled by adhesion molecules. The same growth
      factors and cytokines that promote bone cell differentiation have an important
      role in the prevention of cell death that is usually produced by apoptosis. The
      molecular mechanism of cytokines' and growth factors' actions is the activation
      of the pathway glicoprotein 130/Janus kinases/signal transductors and activators
      of transcription. The final step is the inhibition of cycline-dependent kinases,
      resulting in the inhibition of cell cycle and transition from G1 phase to S
      phase. Osteoblastogenesis and osteoclastogenesis are strongly bound together.
      Osteocytes are the most numerous bone cells, they have a long life, but
      ultimately die by apoptosis.

PMID- 14974210
TI  - [Possibilities and limits of antiretroviral actual therapy].
AB  - The therapies now approved for HIV-infection inhibit one of two viral-specific
      enzymes, reversetranscriptase or protease. Combining this drugs into regimes
      based on at least three individual drugs--so-called HAART--has resulted in a
      remarkable reduction in HIV-associated morbidity and mortality. Despite these
      therapeutic advances, many patients are either intolerant of available agents or
      develop virologic failure. Problems of adherence, drug-resistance, latent
      reservoirs and drug-induced toxic effects that compromise effective viral control
      point to need for new strategies (e.g. structured treatment interruptions--STIs)
      and new classes of anti-HIV drugs with different modes of action (e.g. blocking
      HIV entry into human cells or fusion process). The use of adjunctive immune-based
      therapy such as IL-2 may permit more extensive immune restoration.

PMID- 14974211
TI  - [The assessment of left ventricular function in cardiac and extracardiac
      disorders in children].
AB  - The left ventricle (LV) suffers during various cardiac and extracardiac diseases.
      After the description of the cardiac performance during human development, the
      authors present the assessment of the left ventricle function in some cardiac and
      also extracardiac disorders of the child. There are listed the changes in
      myocardial structure, systolic and diastolic function in hypertrophy and dilation
      of the LV determined by systemic diseases that affect the pediatric patients and
      can lead to severe cardiac failure.

PMID- 14974212
TI  - [Arrhythmogenic right ventricular dysplasia].
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) is a new form of cardiomyopathy
      probably more frequent than commonly reported. The incidence is unknown. ARVD is
      a heart muscle disorder of unknown cause that is characterised pathologically by
      fibro-fatty replacement of the right ventricular myocardium. It is a rare but
      important cause of sudden cardiac death in young, otherwise healthy persons. The
      right ventricle should be extensively sampled histologically in all cases of
      sudden unexpected death, especially those that are exercise related. The disease
      is often familial (about 30%) with an autosomal dominant inheritance.

PMID- 14974213
TI  - [Actualities regarding the degenerative valvular heart].
AB  - The degenerative valvular heart disease became prioritary from the
      epidemiological point of view by contrast with the rheumatismal one, as a
      consequence of the increase of the economic standard and of average life
      expectancy. The calcific aortic stenosis is the most frequently encountered among
      the valvular heart lesions. Since the history of this disease is not well known,
      many efforts have been made in order to research all its aspects from the
      etiology to therapeutical and prophylactic methods.

PMID- 14974214
TI  - [Current treatment of esophageal achalasia. Surgeons' opinion].
AB  - This present paper is proposing a presentation of the current therapeutical
      possibilities in the esophageal achalazia. This severe esophagian motility
      disorder is profiting, in the current context of minim invasive therapy, of
      either pneumatic dilatation, either esocardiomyotonomy. Both methods have given
      favorable results, but degradable in time. Starting from the experience of my
      gastroentheriologists colleagues, presented in previous papers, we insist on
      minim invasive therapeutical gestures. And, because the pneumatical dilatation,
      besides the smaller percentage of favorable results and the need of being
      periodically repeated, determines anatomical alterations of the esopagian
      junction that make difficult and even dangerous the surgical intervention, we
      plead for esocardiomyotonomy from the beginning. The possibility of operating
      videooscopically is imposing this therapeutical method. Regarding the videoscopic
      alternative, we are pleading for the abdominal way and for the Bailey esomyotomy
      or Heller esocardiomyotomy with fundoplicatura.

PMID- 14974215
TI  - Emergency care: the tumor lysis syndrome.
AB  - The Tumor Lysis Syndrome (TLS) is a constellation of metabolic disturbances due
      to the rapid tumoral cell destruction, either spontaneous or induced by
      cytoreduction therapy, which manifests as an acute, subacute or chronic renal
      insufficiency. Hyperuricemia is the hallmark of the TLS. The therapy consists in
      management of hydro-electrolytic and metabolic disturbances, treatment of
      hyperuricemia (Allopurinol and a new therapeutical agent, Uricase), hemodialysis.
      If promptly supported during the TLS, a number of these patients have an
      excellent probability of long-term remission.

PMID- 14974216
TI  - [The role and importance of antidrug educational program in preventing
      toxicomania in adolescents].
AB  - If before 1989 the use of drugs in Romania was an exceptional situation, in the
      last few years our country evolved from a transit area to a potential market. The
      drug users in Romania a coming from all the social classes (workers, unemployed,
      students and even medical staff), but more vulnerable are the adolescents and the
      young unemployed people. There is a certain risk that the drug use in Romania to
      become a wide spread phenomenon, with a tendency of getting out of control. Thus
      we need an operational program in the fight against the drug use.

PMID- 14974217
TI  - [Detection of lymph nodes micrometastases in breast carcinoma using
      immunohistochemistry for cytokeratin 8].
AB  - The lymph nodes status is one of the most important prognostic factors in breast
      cancer. The routine hematoxilin-eosin staining is efficient for the metastases
      detection only when there is a large number of tumor cells, while a small number
      of metastatic cells can easily remain undetectable. For those situations, the
      immunohistochemistry for cytokeratins, markers of the epithelial cells, is a very
      sensitive method. We have investigated the cytokeratin 8 expression in 10 primary
      breast carcinomas and in the corresponding axillary lymph nodes, comparing with
      hematoxilin-eosin. The routine examination has detected axillary lymph nodes
      metastases in six cases, confirmed by the immunohistochemistry for cytokeratin 8.
      Four cases were diagnosed as negative for the axillary lymph nodes metastases by
      the hematoxilin-eosin staining. In all those four cases, immunohistochemistry for
      cytokeratin 8 has detected a small number of tumor cells, either spread in the
      lymph nodes tissues, either confluent as small islets.

PMID- 14974218
TI  - [Diagnosis of gastric cancer on endobiopsies using the WHO classification].
AB  - Gastric cancer (GC), one of the most frequent malignancies can be early detected
      on endobiopsies. Our aim was to evaluate histologically the GC on endobiopsies,
      using WHO 2000 and Lauren classifications. The study included 2424 gastric
      endobiopsies, routine processed; sections stained with HE, Giemsa, PAS and AB. GC
      was diagnosed in 451 cases (19%), mostly in men (311 cases--69%). The highest
      incidence was in 60-69 year-old aged patients (34%). Using Lauren classification,
      279 cases were included in diffuse type (62%), 167 intestinal-type (37%) and 5
      (1%) mixed type. Each of these three types were also histologically analyzed
      considering the WHO classification. We pointed out that GC can be diagnosed
      histologically on endobiopsy specimens, although it is difficult to diagnose the
      GC--mixt type, due to reduced size of endobiopsies. Lauren classification
      (including the two major types: diffuse and intestinal) is very useful,
      especially if correlated with histological criteria of WHO classification.

PMID- 14974219
TI  - [Clinical and epidemiological aspects in patients with colorectal cancer].
AB  - The aim of this study was to evaluate the clinical factors of the patients with
      CCR histologically confirmed. PATIENTS AND METHODS: In the study group there were
      included 117 patients (females: 49-41%, males: 68-59%, range: 39-88 years) with
      CCR confirmed (rectosigmoidoscopy/colonoscopy + biopsy, X-ray) hospitalized in
      the Second Medical Clinic Gastroenterology during January 2000-May 2001. RESULTS:
      For 56 (47.86%) patients the principal sign was rectal bleeding, intestinal
      disorders (diarrhoea--constipation) in 24 (20.51%) patients, anemia in 19
      (16.23%) patients and abdominal pain in 18 (15.38%) patients. The time interval
      between the onset and the diagnosis of CCR was 1 month up to 2.5 years. For 83
      patients (71%) was possible surgical treatment and for 34 patients (29%)
      palliative method. CONCLUSIONS: At diagnosis the clinical data suggested a
      malignant disease for most of the patients. The delay of diagnosis was associated
      with advanced staging of the disease, with limiting therapeutic possibilities.
      Using the screening for CCR may give the possibility for a curative treatment.

PMID- 14974220
TI  - [Transitional cell carcinoma of the upper urinary tract- staging by computed
      tomography].
AB  - PURPOSE: To determine the accuracy of computed tomography (CT) in staging
      transitional cell carcinoma of the renal pelvis and calyces and to identify
      whether hydronephrosis proximal to the tumor used as a criterion for minimal
      invasion may improve the overall accuracy of the method. MATERIALS AND METHODS:
      24 patients with transitional cell carcinoma of the upper urinary tract underwent
      preoperative CT. In all cases nephroureterectomy was performed and CT and
      pathologic staging were compared. RESULTS: Pathologic staging revealed two stage
      I tumors, eight stage II tumors, five stage III tumors, and 9 stage IV tumors.
      The initial overall CT staging accuracy was 66.66% (16 of 24 patients).
      Reevaluation of the CT studies by using proximal hydronephrosis as a criterion
      for minimal invasion improved the overall CT staging accuracy (83.33%).
      CONCLUSIONS: When CT demonstrates direct tumor extension through the pelvic wall,
      it is a sensitive indicator of high-stage tumor. Hydronephrosis proximal to the
      tumor may cause overstaging of stage 0-II disease.

PMID- 14974221
TI  - Pepstatin A is inducing contractile effects on isolated rat aorta rings.
AB  - In a series of experiments dealing with the effects of angiotensin I (AI) and
      angiotensinogen on isolated rat aorta we observed that pepstatin A was able to
      induce contractile effects by itself. The endothelin pathway was excluded by the
      inhibitory effects of captopril, chymostatin and amastatin. In addition, few
      preliminary experiments showed that the contractile effects of pepstatin A were
      inhibited by the pretreatment with losartan, an antagonist of AT1 angiotensin
      receptors. Pepstatin A-induced contractile effects on isolated rat aorta were
      inhibited with high potency by captopril, chymostatin and amastatin and were
      totally blocked by captopril + amastatin and captopril + chymostatin. Finally, we
      concluded that the pepstatin A-induced contractile effects on isolated rat aorta
      rings are dependent on an angiotensinogen vascular pool, compulsory involve an
      angiotensin-converting enzyme-1 (ACE-1) mediated pathway and one or more non
      classical pathways for the generation of angiotensin peptides. Further
      experiments are necessary to elucidate the mechanisms associated to pepstatin A
      induced effects.

PMID- 14974222
TI  - [The cardiovascular reflex tests in autonomic cardiac neuropathy diagnosis].
AB  - Ewing's five standard cardiovascular reflex tests were used for the assessment of
      autonomic function. Changes in heart rate during deep inspiration and expiration,
      Valsalva manoeuvre or standing up evaluate parasympathetic innervation, whereas
      blood pressure fluctuations during standing up and handgrip evaluate sympathetic
      innervation. According to physiological principles we must remind that each test
      is useful predominantly but not exclusively to reveal the impairment of
      parasympathetic or sympathetic innervation. A total of 271 patients (247 with
      diabetes mellitus) were estimated for the diagnosis of autonomic neuropathy.
      Computed time domain analysis of the heart rate variability reveals 21% of the
      patients with autonomic neuropathy, but this method doesn't rich the performance
      of spectral analysis witch is x3 times greater. The deep inspiration and
      expiration remains the preferable test according to its sensibility, specificity
      and predictive value. I found that handgrip test has, beside the known
      limitations (arterial hypertension, heart failure, valvular disease, emphysema,
      advanced diabetic retinopathy, drugs like digitalis, beta-receptor blockers,
      antihypertensives, sedatives, etc.) one more linked by the hand muscular force.
      Orthostatic hypertension has too many false results so the interpretation must be
      done with much precaution.

PMID- 14974223
TI  - [Knodell and Metavir scoring systems--advantages and limits].
AB  - The study relies upon the analysis of hepatic biopsies from 36 adults
      hospitalised in "Infections Disease Clinical Hospital" Iasi. The clinical
      diagnosis was chronic hepatitis. The histological exam revealed 33 cases of
      chronical hepatitis, 1 case of cirrhosis, 2 cases are still open to
      interpretation. The lesions have been interpreted according to Knodell and
      Metavir scoring systems. The scores are significantly important in identifying
      the grades of histological activity and the stages of the fibrosis. The result of
      these scoring systems allow the classification of the cases into aggressivity
      based forms, the estimation of the prognosis and offer indication in therapy.

PMID- 14974224
TI  - [Morphometrical analyze of the middle cerebral artery system at the 13-15 weeks
      fetuses].
AB  - Tele-encephalization process is accompanied by the appearance and progressive
      complication of the middle cerebral artery system. The aim of our study is to
      analyze the morphometrical parameters of the middle cerebral artery branches in
      the beginning of the edification of its system. We used 162 cerebral hemispheres
      from 88 fetuses aged of 13-15 weeks. Middle cerebral artery system was injected
      with a gelatin-China ink mixture and images recorded by means of a Zeiss surgical
      microscope. Parameters evaluation (length, proximal and distal diameters,
      external surface, volume, angles of bifurcation) was realized with KS-300
      program. At this early age middle cerebral artery system has only 4-5 generations
      of branches usually resulting from acute angle bifurcations.

PMID- 14974225
TI  - [Pediatric ocular trauma. Retrospective study 1997-1999].
AB  - The aim of this study is to identify the major mechanisms and the aetiology of
      ocular trauma in children population. It is a retrospective study of 138 children
      treated for ocular injuries in Clinica I Ophthalmology, between 1 January 1997
      and 31 December 1999. The mean age of study was 9.9 years for girls and for boys
      10.7 years. Boys were more frequently involved as girls (ratio 3.6/1). Injuries
      were in 25% to have occurred at home and in 46% with their own toys. In
      conclusions, ocular trauma occurs most frequently in the home setting, after
      sharp tools. It is necessary to treat trauma early and complete for prevention
      amblyopia.

PMID- 14974226
TI  - [Male gender-- difficulty factor in cholecystectomies for cholelithiasis].
AB  - Male gender has been recognized as a risk factor for an increased conversion rate
      of laparoscopic cholecystectomy and more severe disease in those with symptomatic
      cholelithiasis. The aim of this study was to determine the effect of male gender
      on the clinical presentation of symptomatic cholelithiasis, relation between male
      gender and acute cholecystectes, the operating time, the frequency of conversion
      and postoperative morbidity. The medical records of all patients with symptomatic
      cholelithiasis from 31 mars 1993 to 31 mars 2001 (4145 patients) were evaluated.
      These cases were divided into four groups: A--elective laparoscopic
      cholecystectomy group--patients with cholecystectes with elective laparoscopic
      cholecystectomy (3995 cases); B--patients with acute cholecystectes whose
      laparoscopic cholecystectomy was performed successfully (660 cases); C--acute
      conversion group converted to open surgery (240 cases); D--acute open group with
      elective open cholecystectomy. The study reveals that males suffer from a severe
      form of cholecystectes that raise difficulties when laparoscopic cholecystectomy
      is performed.

PMID- 14974227
TI  - [Diaphragmatic blunt injuries: analysis of cases].
AB  - Blunt injuries of diaphragm are frequently encountered in polytrauma and thoraco
      abdominal injuries. Between 1992/2001, 12 cases were analyzed, representing
      19.64% of of a total of 52 cases with diaphragmatic injuries (12 blunt and 40
      penetrating). 11 were victims of traffic accidents (91.66%) and one of
      precipitation (8.3%). There were six men and five women. When they were admitted
      all patients presented with signs of trauma and hemorrhagic shock. 11 cases were
      operated. On the first 3 hours and in 3 cases, the patients were directly
      transported in operator theatre. Death rate was quite high--27.27%. Hospital stay
      was 15.54 days in average (13-38 days). Complication rate was 27.3%.
      Diaphragmatic injury are life threatening injuries, always challenging,
      associated with a high rate of mortality.

PMID- 14974228
TI  - [Recurrent abdominal pain and genital diseases in young girls].
AB  - Recurrent abdominal pain represents one of the most frequent syndrome met in
      pediatrics pathology at all ages, sometimes raising difficulties in establishing
      the diagnosis. One of the most frequent causes of recurrent abdominal pain is the
      genital disease at young girls. A retrospective study realized on a 10,000 girls
      lot, consulted in pediatrics offices from St. Spiridon Hospital of Iasi, between
      1999-2001, emphasized the presence of recurrent abdominal pain and genital
      pathology at 300 young girls, that is 25% of the cases with genital diseases and
      12% of the cases recurrent abdominal pain. Genital pathology means represented
      by: dysmenorrhea in 36% of cases, pelvic inflammatory disease in 26.67% of cases,
      functional ovarian cyst in 6% of cases, ovarian tumors in 0.33% of cases, ectopic
      pregnancy in 0.33% of cases, vulvovaginitis in 27.67% of cases. The most affected
      age was 13-16. The study of those diseases related to a genital pain diagnosed as
      responsible, ethiologically, for the recurrent painful abdomen, confirmed the
      existence of a very tight correlation between the genital pathology and the
      general one.

PMID- 14974230
TI  - [Road accidents morbidity and mortality in district of Vrancea].
AB  - Nowadays, road accidents represent an important cause of morbidity and mortality.
      The present paper is a descriptive study of the most important factors involved
      in road accidents appearance from the district of Vrancea, in year 2001 and
      assesses the gravity of premature deaths using potential years of lost life
      (PYLL). In this district, the level of PYLL due to road accidents in male is
      significant higher in comparison with female (964 and respectively 408), these
      data being in concordance with PYLL of the entire country. The most frequent
      causes involved in road accidents are related to human factor and less to vehicle
      or road conditions. This category of trauma and deaths may be entirely prevented
      through educational, law, control or technical measures and using descriptive
      epidemiological data regarding road traffic.

PMID- 14974229
TI  - Variation of carboxyhemoglobin and of thiocyanates in smokers.
AB  - Smoking is one of the most important public health problems of our times. In this
      paper, we focus on the watching of smoking effect on carboxyhaemoglobin (COHb)
      and plasma thiocyanate values. The study was accomplished on two groups of blood
      donors: smokers, 18 men, between 20-51 years old and controls, non-smokers, 10
      men, between 22-55 years old. On the blood samples, there have been
      spectrophotometrically determined: COHb with palladium chloride by microdiffusion
      method and haemoglobin (Hb) with Drabkin Reagent. The plasmatic thiocyanates were
      determined spectrophotometrically by Liebig reaction. The data were processed by
      "t Student" test. The statistical analysis shows that the obtained average values
      for the COHb from total Hb in smokers (12.51 +/- 10.19) are higher than the
      average values of the control group (11.45 +/- 10.34). The plasma thiocyanate (mg
      %) in the smokers' group presents average values of 2.03 +/- 0.58, higher values
      than those in the control group (1.68 +/- 0.68). From the analysis of the
      presented results, we notice that the differences between the two groups are
      statistically non-significantly. These results may be explained by the existence
      of many factors, which may influence the values of the biotoxicological
      indicators, among which we mention: passive smoking, the atmospheric pollution in
      the urban environment, the presence of the chemical noxae at the work place.

PMID- 14974231
TI  - [Cognitive level and behaviour in nutritional health education in a group of
      parents].
AB  - In the last years, the education for health developed itself rapidly, due to the
      close relationship between scientific development and social life dynamics. The
      relation between the cognitive level, behaviour and nutrition was assessed in a
      group of parents with children 9 to 12 years of age. The majority of the parents,
      and also of children, have an adequate cognitive level, knowing very well the
      basic principles of a sanogenic diet. Many parents give as their information
      source the mass-media, and especially the television, the education for
      nutritional health must be reconsidered, in order to have a greater impact in
      preserving the health status of the individual.

PMID- 14974232
TI  - [Preclinical assay on a magnetic carrier type ferrofluid].
AB  - The aim of the study was to determine the acute toxicity and the antimicrobial
      actions of an original magnetic carrier, type ferrofluid. The hydrophilic
      ferrofluid was prepared by covering the Fe3O4 nannoparticles with ammoniumoleate.
      The absolute amount of iron was of 40 mg/ml ferrofluid. METHODS: Acute toxicity
      was evaluated on five groups of Swiss male mice, after a single intraperitoneal
      administration of 1, 0.75, 0.5, 0.25 and 0.125 ml dose of pure ferrofluid/100 g
      body weight (b.w.), using step-level toxicity method. The study groups of mice
      were follow-up for 10 days. We did not use the same volume of solution for all
      the study groups because we were concerned about not to modify the behavior of
      the ferrofluid (but for each group we used the same volume of solution). The
      tasks of this part of the study were: 1) the record of the mice death in the
      first 10 days after intraperitoneal administration of ferrofluid; 2) the behavior
      of the animal subjects; 3) the morphopathologic examination of kidney, lung,
      heart, liver and peritoneum samples from the death mice and from the after ten
      days survivors which were sacrificed. We also investigated the possible
      antibacterial actions of the ferrofluid on E. coli spp., Klebsiella spp.,
      Staphylococcus aureus Streptococcus group D., in the second part of the study,
      using standard lab kit. The validation of the results was performed using
      controls for E. colli and Staphylococcus aureus. RESULTS: The death of the mice
      was registered between 24 and finished after 96 hours. The maximum tolerated dose
      (MTD), was of 0.25 ml (10 mg iron/100 g b.w.) and the lethal dose hundred percent
      (LD100) was of 0.75 ml/(30 mg iron/100 b.w.). In our study we did not determined
      any kind of antibacterial action of the ferrofluid. CONCLUSIONS: 1) LD100, in our
      study, was of 30 mg iron/100 g b.w., and DMT of 10 mg iron/100 g b.w. 2) The
      death of the mice may be due to toxic aggression of ammonium ions released, in
      vivo, from the ammoniumoleate coverage of magnetite nannoparticles. 3) There were
      no in vitro antibacterial actions for this ferrofluid.

PMID- 14974233
TI  - [The experimental evaluation regarding analgesic activity of some extracts
      isolated from Achillea collina J. Becker ex Reichenb].
AB  - In the present investigation we have evaluated the potential existence of
      analgesic activity of the residue of tincture and of the crude lipophilic (AC 2,
      AC 4) and hydrophilic portions (AC 1, AC 3) of infusion and decoction obtained
      from flower heads of Achillea collina J. Becker ex Reichenb. Acid acetic induced
      writhing and vascular permeability test was performed by the method of Whittle.
      Comparison was made with indomethacin, morphine and rutin, as references drugs.
      The mice were dosed orally with samples. AC 2 induced a potent inhibition
      (47.23%; p < 0.05) of the nociceptive response after oral administration of 250
      mg/kg--a dose ten folds higher than the dose of indomethacin. AC 3, at a dose of
      5000 mg/kg (p.o.) inhibited with 47.6% (p < 0.001) and 19.8% (p < 0.05) the
      increase in peritoneal vascular permeability caused by 0.5% acetic acid. Relative
      unexpected, morphine (1.14 mg/kg, p.o.), an opioid analgesic, also produced a
      significant reduction of the leakage (41.2%, p < 0.01). This finding is
      consistent with the reports in which the role of the endogenous opiate system in
      the physiological response to injury/inflammation, mainly controlling fluid
      leakage into the interstitial space, is sustained.

PMID- 14974234
TI  - [An experimental study of tolerance to benzodiazepines].
AB  - The intention of the study was to demonstrate the appearance of the tolerance
      phenomenon after repeated administration of three of the most used benzodazepines
      (BDZ): Diazepam, Alprazolam and Oxazepam using three pharmacological tests, which
      monitored the neuromotor coordination, the myorelaxing and the anxiolitic effect.
      For each drug were used 3 doses, in geometrical progression, beginning with the
      partial dose, extrapolated from human to mouse according to the body surface. The
      treatment was made once a day, during 4 days. The appearance of tolerance was
      noticed, meaning an approximately 4-fold decrease of the sedative effect after
      the repeated administration of the 3 BDZ for all doses used. No tolerance was
      shown for the anxiolytic and myorelaxing effects, with the exception of
      alprazolam, which induced tolerance also for the myorelaxing effect. Our study
      has shown that repeated administration of BDZ might have different consequences
      on their pharmacological spectrum. The study indirectly explains the success of
      Alprazolam in therapy. This is due to the fact that small doses have
      approximately the some efficiency as the big ones in unique administration,
      decreasing the abuse potential. The rapid onset of the tolerance for the sedative
      and myorelaxing effect recommends its long-term administration in anxiolytic
      therapy.

PMID- 14974235
TI  - Cardiac consequences of the systemic lupus erythematosus therapy with
      corticosteroids morphological study.
AB  - It is presented the case of a fifty years old women, diagnosed 3 years ago with
      systemic lupus erythematosus, under therapy with prednisone and cyclophosphamid
      therapy. She was admitted in our hospital for right decompensated heart disease
      and the presence of an apical right ventricular mass occluding part of the right
      ventricular cavity. The endomyocardial biopsy was made to clearify the nature of
      this mass. After processing the specimen, the histological study evidenciated an
      organizing apical thrombotic mass formed in a large right ventricular cavity in
      conditions of pulmonary hypertention. There are presented data concerning the
      adverse effects of the systemic lupus erythematosus drug therapy, as well. In
      these circumstances, we demonstrated histologically, that both conditions could
      alter the heart morphology.

PMID- 14974236
TI  - Thoracoscopic sympathectomy for upper limb ischemic disease.
AB  - We treated in 2001 in our clinic two patients with upper limb ischemic disease.
      Both patients had chronic pain and cyanosis of the fingers, with trophic
      disorders and partial amputations of distal phalanges. They were previously
      submitted to medical treatment with no result. We present the technique used,
      resectional thoracoscopic sympathectomy including T2 and T3 ganglia. First of the
      patients was operated on bilaterally in two successive operations, the second one
      only on the right side. There was an uneventful postoperative evolution with good
      immediate and short term results.

PMID- 14974237
TI  - [Osler--Rendu Disease: an example of a family clustering in a genetic disorder].
AB  - The case of a 75 years old woman with hereditary hemorrhagic telangiectasia (HHT)
      is presented. This condition is an autosomal dominant mucocutaneous and visceral
      fibrovascular dysplasia in which telangiectasia, arteriovenous malformations and
      aneurysms may be widely distributed throughout the cardiovascular system. It is
      usually recognized as a "triad" of telangiectasia, recurrent epistaxis and a
      family history of the disorder.

PMID- 14974238
TI  - [Chronic lead poisoning-- a" forgotten" cause of anemia].
AB  - We present the case of a female patient with a chronic hypersideremic anemia
      associated with digestive and neurological symptoms, with a long time ignored
      toxic history. The diagnose was based on very high levels of lead in serum and
      urine, very high levels of D-aminolaevulinic acid in the urine, and the presence
      of basophilic stippling of erythrocytes in the smear of the patient. Lead
      intoxication was due to ingestion of home-made alcohol (domestic devices made
      from lead mixtures) and of yogurt preserved in lead-glazed mugs.

PMID- 14974239
TI  - Two cases of Marfan syndrome.
AB  - The early identification of the Marfan Syndrome should be essential for the
      prevention of the aortic dilatation and dissection, but the wide phenotypic
      expression of the disorder makes the clinical diagnosis very difficult. The aim
      of this study is to emphasise the necessity of a widely applicable method of
      morpho-clinical diagnosis. The diagnosis was confirmed on surgical biopsies from
      ascending aortic wall and aortic cusps, using routine morphological techniques.
      The macroscopical examination revealed a thin ascending aortic wall, presenting a
      transversal intimal tear, without secondary dissecting hematoma, and an aortic
      dilated annulus, producing aortic regurgitation. Microscopically, the diagnosis
      was supported by the identification of cystic medical necrosis, a specific
      degenerative lesion in the Marfan Syndrome, in patients with or without family
      history of aortic aneurysms. This study defines the morpho-clinical changes of
      the disease, emphasising the necessity of a permanent monitorization of the
      patient after surgery, due to the risk of late complications.

PMID- 14974240
TI  - [2 cases of Lowe syndrome].
AB  - Lowe syndrome is a form of X-linked mental retardation with short stature,
      cataracts, renal tubular dysfunction and hypotonia. We present 2 cases to
      illustrate this rare entity, but also to discuss the suggestive aspect of the
      face and to underline the importance of molecular tests for genetic counselling.
      Both cases associate ocular, cerebral and renal defects. Molecular tests changed
      the recurrence risk in the first family.

PMID- 14974241
TI  - [ Rare sites of hydatic cyst].
AB  - The aim of this case report is to underline that the hydratic disease is still a
      healthcare problem in our country. Moreover, the atypical site of the cyst, as
      shown in the report, is a rare event and sometimes, an intraoperative or
      histological finding. Difficulties could arise from the operative management,
      during the radical procedures, to preserve some anatomic important structures.
      Modern imagistic data will certainly improve the preoperative diagnosis.

PMID- 14974242
TI  - Wireless capsule endoscopy--a novel technique for visualising the gut.
AB  - This review is presenting the "capsule endoscopy", a developing method for
      visualizing the gut and especially its "dark" areas, the small intestine. It is
      presented its description, and the evaluation of its present indications. The
      capsule endoscopy is good for identifying bleeding of unknown origin, tumors and
      inflammatory lesions of small bowel. Capsule endoscopy seems to be an expanding
      method for investigating the gut.

PMID- 14974243
TI  - [Proposal for macroscopic examination of the heart , of the great vessels and of
      the lungs in forensic pathology].
AB  - Our work presents a kind of proceeding for the cardio-pulmonary dissection and
      forensic examination. As a result of the necessity to have right from the time of
      the autopsy more clear data regarding the cause of death, in order to be able to
      direct the judicial investigation towards a certain type of death, this
      proceeding presents, in our opinion, several important advantages--in comparison
      to the common examination method--such as the facility macroscopic diagnosis in
      some heart diseases: arrhythmogenic displasy of the right ventricle, mitral valve
      prolapse and other valvulopathies.

PMID- 14974244
TI  - [The role of intravenous urography in the diagnosis of urinary tract lithiasis in
      the era of new therapeutical methods].
AB  - Urinary stones continue to be an interesting and major problem for both
      urologists and radiologists. The authors try to present the imaging diagnosis
      possibilities for this pathology according to the expectations of the urologists
      who have to deal with urinary tract lithiasis with the new methods
      (extracorporeal shock wave lithotripsy, percutaneous nephrolithotomy, and
      ureteroscopy). Helical CT has certain advantages and in different centers in
      Europe appear to be less expensive than intravenous urography (IVU), but
      unfortunately, is not available in our medical center. So, for us, IVU remains
      the basic investigation for urinary stones. Echography helps a lot for correct
      strategy, but together with KUB cannot replace IVU if we want to avoid mistakes.

PMID- 14974245
TI  - [Clinical competitive examination in surgery].

PMID- 14974246
TI  - [Professor doctor Alexandrina Gaiginschi ( 23 July-28 December 2002)].

PMID- 14974247
TI  - Your latest legal threat: consumer fraud.

PMID- 14974248
TI  - Coding: what's new in 2004.

PMID- 14974249
TI  - Group practice. The IRS cracks down on bonuses.

PMID- 14974250
TI  - An odd practice booster--my nurse quit.

PMID- 14974251
TI  - Are you taking HIPAA too far?

PMID- 14974252
TI  - Toward better senior healthcare.

PMID- 14974253
TI  - If the computer ate your charts.

PMID- 14974254
TI  - Let's be realistic about countersuits.

PMID- 14974255
TI  - The shape of things to come.

PMID- 14974256
TI  - The predictions of nursing leaders.

PMID- 14974257
TI  - Reinventing the nursing role.

PMID- 14974258
TI  - Sharing best practice across the Atlantic.

PMID- 14974259
TI  - The outlook for a new generation. Interview by Alison Whyte.

PMID- 14974260
TI  - Food allergies, food intolerance and food-related anaphylaxis.
AB  - The incidence and complexity of allergic disease has increased dramatically in
      the UK in recent years. Existing services are inadequate and need to be expanded
      so that patients with complex allergic conditions can be treated by allergy
      specialists and members of the primary health care team can be given training to
      enable them to teat non-complex cases.

PMID- 14974261
TI  - What you need to know about ... personality disorder.

PMID- 14974262
TI  - The role of EEGs in the treatment and prognosis of epilepsy.
AB  - The significance of what is recorded in an electroencephalogram (EEG) can be
      easily misunderstood or misinterpreted. Even after years of use, it is still not
      an exact science. There appear to be many possible uses of the EEG but no clear
      agreement on its best use. Even its role in assessing the treatment, severity,
      progress and prognosis of epilepsy is varied. The need to find answers to
      questions around areas such as severity, treatment, progress and prognosis seems
      to be detracting from the area that the EEG can provide most help in: the
      classification of epileptic syndromes.

PMID- 14974263
TI  - The development of an online quiz for drug calculations.
AB  - This article describes the development and implementation of an online drug
      calculation quiz. The multiple-choice quiz was designed to help staff to identify
      their learning needs and reduce the incidence of medication errors. The system
      implemented shifted the responsibility of training from trainer to learner and so
      promoted individual accountability.

PMID- 14974264
TI  - The challenge of managing patients with multiple sclerosis.
AB  - Multiple sclerosis (MS) is the most common cause of neurological disability in
      young adults in the UK. It is variable in presentation and progression. Although
      there is no cure, there are many symptomatic treatments available. Nurses have a
      vital role in the ongoing assessment and management of people with MS.

PMID- 14974265
TI  - Acute wounds: an overview of the physiological healing process.
AB  - When an injury occurs and the skin is damaged, the process of tissue repair
      begins immediately, but some wounds can take up to two years or more to heal
      completely. Healing is usually categorised into stages to aid understanding of
      the complex physiological processes that are occurring. However, it is a
      continuous process and different parts of a wound may be at different stages of
      healing at any one time.

PMID- 14974266
TI  - Procedures for cleansing, closing and covering acute wounds.
AB  - Every wound and patient is different so there is no single method for the
      management of acute wounds. However, there are some guiding principles that can
      assist in the decision-making process. Most wounds are suitable for primary
      closure, for example with sutures, while for other wounds closure is either
      delayed or not attempted (healing by secondary intention). Atiyeh et al (2002)
      provide a list of the principles of wound care that must always be observed in
      order to avoid sepsis and to achieve optimal wound healing (Box 1).

PMID- 14974267
TI  - The protective effects on wound edges of a new preparation.
AB  - Marked progress has been made in the management of chronic wounds in recent
      years. However, every attempt to protect the wound edges has been unsatisfactory
      and in many cases the products used were not developed for the purpose of skin
      protection.

PMID- 14974268
TI  - Evaluating the effectiveness of Tegapore wound-contact material.
AB  - During wound healing, new-forming granulation tissue is often extremely fragile
      and can be easily disrupted during dressing changes. This can lead to a delay in
      the completion of wound healing and increased pain and discomfort for the patient
      (European Wound Management Association, 2002; Fear, 2002).

PMID- 14974269
TI  - [Low yield of HPV DNA determination in the distal region of the male urethra].
AB  - OBJECTIVE: To assess the prevalence of Human Papillomavirus (HPV)
      Deoxyribonucleic acid (DNA), and of clinical and subclinical condilomatosis in
      men whose sex partners had been diagnosed with cervical intraepithelial
      neoplasia. MATERIAL AND METHODS: A cross-sectional study was conducted from
      October 1997 to August 1998, among 200 men aged 17 to 64 years referred to the
      Oncology Department of the National Institute of Perinatology in Mexico City. A
      physical examination of the penis (penoscopy) was performed after applying 3-5%
      acetic acid. A colposcope was used to identify acetowhite areas and vascular
      abnormalities associated with HPV infection. HPV DNA was detected by PCR and
      reverse line hybridization. The exploratory and univariant statistical analysis
      was made with the package Stata V6.0. RESULTS: The beta-globin gene was present
      in 93.5% (n = 187) of the 200 urethral exfoliated cell samples collected. HPV DNA
      was detected in only 2% (4/187) of the study subjects. Penoscopy data showed the
      presence of acetowhite areas in 43% (81/187) of subjects. CONCLUSIONS: Study
      findings show that the presence of HPV DNA in urethra is uncommon, as has been
      reported in several previous studies. Research is needed to evaluate the presence
      of HPV DNA in the coronal sulcus, as compared with the distal urethral region.
      The English version of this paper is available
      at:http://www.insp.mx/salud/index.html.

PMID- 14974270
TI  - [Affection, kisses, and condoms: the ABC of sexual practices of female sex
      workers in Mexico City].
AB  - OBJECTIVE: To describe and explore the meanings of sexual practices among female
      sex workers (FSW) in Mexico City. MATERIAL AND METHODS: A qualitative and
      quantitative study was carried out. The qualitative approach was conducted in
      1992 and the latter from 1991 to 1992. The study population was a representative
      sample of FSW (n = 335) who completed a questionnaire; 52 of them also
      participated in six focal groups. Simple frequencies, central trend, and
      dispersion measures were calculated. Qualitative data were interpreted using
      Grounded Theory and a feminist perspective. RESULTS: Female sex workers accepted
      vaginal penetration with clients and oral penetration to a lesser extent, while
      anal penetration and kissing were rejected. All sexual modalities were accepted
      with personal partners. In their practice, FSW use psychophysical dissociation as
      a psychological defense mechanism and to construct their identities. Services
      requested by their latest clients were: 98.4% vaginal, 39.1% oral, and 7.7% anal
      sex. Condom use was reported by 94%. With their personal partner, 72.6% of FSW
      never used condoms. The week before the study, FSW worked 3.7 +/- 1.5 days on
      average and had sexual intercourse with 8.6 +/- 8.1 clients. CONCLUSIONS:
      Interventions are needed to promote safe sex among FSW in their private and
      professional lives. The English version of this paper is available
      at:http://www.insp.mx/salud/index.html.

PMID- 14974271
TI  - [Seroprevalence of type 2 herpes simplex virus infection in 3 population groups
      of Mexico City].
AB  - OBJECTIVE: To determine the seroprevalence of type 2 herpes simplex virus (HSV-2)
      infection and risk factors in three female population groups in Mexico City.
      MATERIAL AND METHODS: A cross-sectional study was carried out in 2000, among a
      sample population of women living in Mexico City, diagnosed with breast or
      cervical cancer, and women with negative Pap test results from the general
      population. Informed consent was obtained from all participants to answer a
      sociodemographic and sex life questionnaire and draw a blood specimen. The
      presence of antibodies against type 2 herpes simplex virus was determined using
      the type-specific Western blot technique. Crude and adjusted statistical analyses
      were performed on the associations between survey data and infection outcomes.
      RESULTS: Women with cervical cancer had a seroprevalence of HSV-2 infection of
      46.8% (191/408); that of women from the general population who were Pap negative
      was 29.3% (214/730). For women with breast cancer, the seroprevalence was 22.6%
      (29/128). Variables significantly associated with seropositivity against HSV-2
      infection were older age, more sexual partners, having cervical cancer, and,
      among cervical cancer patients, beginning sexual activity before 21 years of age
      and being divorced or separated. CONCLUSIONS: Study findings showed statistically
      significant differences in the prevalence of viral infection by population
      groups. The overall frequency of viral infection among study subjects shows that
      this is an intermediate risk population, as compared with other population groups
      in Mexico at high (sexual workers) and low (college students) risk. The main
      characteristics associated with exposure to type 2 herpes simplex virus for the
      subpopulations corresponded, as expected, to sexual behavior and to the
      probability of infection with older age. The English version of this paper is
      available too at:http://www.insp.mx/salud/index.html.

PMID- 14974272
TI  - [Prevalence and factors associated with syphilis and genital herpes in 2 groups
      of the female population].
AB  - OBJECTIVE: To assess the frequency of HSV-2 and Treponema pallidum markers and
      their relationship with characteristics of women during gynecological outpatient
      visits. MATERIAL AND METHODS: In 1994 and 1995, two populations of 388 and 448
      women were studied in two hospitals; one in Cuernavaca, Morelos, Mexico, and the
      other in Mexico City. Participants provided a blood specimen for detection of
      antibodies against HSV-2 and T pallidum using the Western blot technique and the
      VDRL and FTA-ABS tests. Also, participants answered a questionnaire on their
      sociodemographic characteristics and sexual behavior. The data were analyzed with
      the SPSS and EGRET statistical packages. RESULTS: The frequencies of HSV-2
      antibodies were 28.3% in women from the first hospital, and 18.1% for those in
      the second. The frequencies of T pallidum antibodies were 2.3% and 1.1%,
      respectively. Age, marital status, education level, and number of sexual partners
      were associated with HSV-2 infection. CONCLUSIONS: Low frequencies were found for
      infection by the microorganisms studied in both groups. HSV-2 infection was
      associated to exposure periods, sexual behavior, and socioeconomic level. The
      English version of this paper is available
      at:http://www.insp.mx/salud/index.html.

PMID- 14974273
TI  - [Social representation of AIDS among students of Mexico City].
AB  - OBJECTIVE: To analyze the social representation of AIDS in a group of high school
      students aged 16 to 23 years in Mexico City. MATERIAL AND METHODS: A non
      probabilistic, cross-sectional research was carried out in a public high school
      in Mexico City. Students of all grades were invited to participate in the study,
      which took place between 1999 and 2000. Forty-six students participated; 28% male
      and 72% female. This exploratory field study consisted of three phases, each to
      address one of three dimensions: cognitive using free association techniques,
      representational field using semi-structured interviews; and context attitude by
      means of two discussion groups. In the latter, the information was previously
      collected for discussion. RESULTS: The cognitive nucleus on AIDS included the
      association between sex, disease, and death. The representational field of AIDS
      is constructed around the transmission-prevention unit. Construct elements are
      virus, contagion, sex, protection, and condom. An ambivalent attitude was
      identified towards HIV prevention and transmission: "We are only half
      responsible". Situations such as "rape, blood transfusions, infected syringes"
      were prominent in the discussion group, deemed beyond their control to prevent
      transmission, thus explaining the group's ambivalent attitude towards prevention.
      The usefulness of condoms was associated with prevention of pregnancy rather than
      with prevention of sexually transmitted infections. CONCLUSIONS: The social
      representation of HIV/AIDS in young students conforms a multidimensional corpus
      where different elements of scientific order and common sense converge and
      interact, such as beliefs, myths, taboos, and fears. All of these contribute to
      construct the meaning of AIDS. The English version of this paper is available
      at:http://www.insp.mx/salud/index.html.

PMID- 14974274
TI  - [Use of condoms among Mexican adolescents for the prevention of sexually
      transmitted diseases].
AB  - OBJECTIVE: To investigate the current sexual behavior and condom use during the
      first sexual intercourse among adolescents, as well as variations and factors
      influencing condom use at first sexual intercourse. MATERIAL AND METHODS: The
      data source for this study was Mexico's National Health Survey 2000. Study
      subjects were male and female adolescents aged 12 to 19 years (n = 16,258).
      Statistical analysis consisted of descriptive statistics and multivariate
      logistic regression, to assess the association of four types of factors
      (demographic, socioeconomic, cultural, and cognitive) with condom use during the
      first sexual intercourse. RESULTS: Males and residents of urban areas reported
      greater sexual activity and condom use. Typically, adolescents who used condoms
      during the first sexual intercourse were male, older, resided in urban areas, non
      speakers of an indigenous language, and with higher schooling. CONCLUSIONS: New
      policies should be framed to prevent sexually transmitted infections to span the
      gap between knowledge and practice, targeting adolescents starting sexual
      activity earlier, those who speak an indigenous language, living in rural areas,
      with less schooling, and females. The English version of this paper is available
      too at:http://www.insp.mx/salud/index.html.

PMID- 14974275
TI  - Sexually transmitted infections associated with vulvovaginal symptoms in
      adolescents denying sexual activity.
AB  - OBJECTIVE: To identify clinical, laboratory and ultrasonographic evidence of a
      probable sexually transmitted infection associated with vulvovaginal symptoms in
      adolescents denying sexual activity. MATERIAL AND METHODS: The medical records of
      female adolescents, aged 10-18 years were reviewed. These women received first
      time medical care for vulvovaginitis, between 1995 and 1999 at Hospital Infantil
      de Mexico Federico Gomez, (Children's Hospital). Comparisons between groups were
      performed, as appropriate, by the unpaired Student's t-test, the Z test or the
      chi-square test; statistically significant differences were set at a two-tailed p
      < 0.05. Odds ratios with 95% confidence intervals were calculated. RESULTS: Of
      258 adolescents with vulvovaginitis, 53 (20.5%) had a sexually transmitted
      microorganism and 52 of them denied ever having sexual activity. Age, education
      and socioeconomic level, development of sexual characters, and presence of
      menstruation did not differ between patients with and without sexually
      transmitted infections. The presence of sexually transmitted infections was
      associated with lower abdominal pain, abnormally colored vaginal discharge, a
      positive urine culture, and an abdominal ultrasonographic evidence, compatible
      with pelvic inflammatory disease (ultrasonographic odds ratio 144.8; 95% CI 51.0
      to 411.3). CONCLUSIONS: There is an association between sexually transmitted
      infections in young women with vulvovaginitis and lower abdominal pain,
      abnormally colored vaginal discharge, a positive urine culture, and an abdominal
      ultrasonographic evidence compatible with pelvic inflammatory disease. The
      English version of this paper is available too
      at:http://www.insp.mx/salud/index.html.

PMID- 14974276
TI  - [Identification of meeting places of sexual partners in 2 cities of the Southern
      Mexican borders, using the PLACE method].
AB  - OBJECTIVE: To identify the meeting sites of new sexual partners in two Southern
      border cities in Mexico. MATERIAL AND METHODS: A descriptive epidemiologic study
      was carried out in May 2001, by surveying key informants in two border cities.
      Each reported site was visited to interview a resident subject. Subjects
      socializing in a subsample of sites were also interviewed. RESULTS: The key
      informants of the community reported 134 meeting sites in Chetumal and 111 in
      Ciudad Hidalgo. Both sites had scarce HIV/AIDS prevention activities.
      Characteristics were obtained for 89 sites in Chetumal and 42 in Ciudad Hidalgo.
      Almost 21% of interviewees reportedly met a new sexual partner in these sites in
      the past four weeks. CONCLUSIONS: Preventive actions are needed in meeting sites
      of new sexual partners. This method may provide information to plan for future
      interventions. The English version of this paper is available too
      at:http://www.insp.mx/salud/index.html.

PMID- 14974277
TI  - [Chlamydia trachomatis infection in women using 2 family planning clinics].
AB  - OBJECTIVE: To determine the prevalence of Chlamydia trachomatis in women
      attending two family planning clinics in Merida, Yucatan, Mexico. MATERIAL AND
      METHODS: From January to December 1998, a cross-sectional study was conducted in
      1,100 sexually active women between 15 and 45 years of age. Study subjects had
      not received antibiotic therapy for at least one month prior to their visit to
      the clinic. Endocervical samples were taken for bacterial detection with the
      enzymatic Wellcozyme immunoassay method. Data were analyzed using the Epi-Info
      program. Statistical analysis was conducted using the chi-squared test and
      prevalence ratios. RESULTS: Seventy four women were positive to Chlamydia
      trachomatis (6.7%). Almost 50% of those women were asymptomatic. No statistically
      significant differences were found between the group with Chlamydia and the group
      without it who had vulvar-vaginal symptoms. Cervical changes were more frequent
      in infected women. More positive cases of Chlamydia infection were found in oral
      contraceptive users (8.3%) than among non users (5.4%). CONCLUSIONS: Study
      results confirm the high prevalence of asymptomatic infections and emphasize the
      importance of timely diagnosis to avoid infection sequelae. The English version
      of this paper is available at:http://www.insp.mx/salud/index.html.

PMID- 14974278
TI  - Sexual behavior patterns and HIV risks in bisexual men compared to exclusively
      heterosexual and homosexual men.
AB  - OBJECTIVE: To compare patterns of sexual behavior among bisexual, heterosexual
      and homosexual men. MATERIAL AND METHODS: A household probability survey was
      carried out in Mexico City in 1992-1993 using the national health surveys
      sampling frame. Information from 8,068 men was obtained; however, the main
      analysis of this paper refers only to men sexually active in the previous 5
      years. RESULTS: Bisexuals reported more prevalent anal intercourse with women
      (16% vs. 3%, p = 0.01), and more sexual encounters with female sex workers than
      exclusive heterosexuals (10% vs. 4%; p = 0.04). Bisexuals used condoms more often
      with sex workers than did heterosexuals (p = 0.01). Most of the bisexuals (79%)
      did not engage in anal receptive or insertive intercourse with males in the
      previous year, practicing instead oral insertive sex or only masturbation; 35% of
      homosexuals did not report practicing anal sex. Bisexuals who engaged in anal
      intercourse had less anal receptive behavior than homosexuals (13% vs. 60%, p <
      0.01); of these, due to condom use, only 7% of bisexuals and 18% of homosexuals
      had unprotected anal receptive sex in the last intercourse with a male.
      CONCLUSIONS: Bisexuals practice less risky sexual behavior with males than
      exclusive homosexuals. This finding may imply that bisexual men in Mexico are an
      ineffective epidemiological bridge for HIV transmission. The English version of
      this paper is available too at:http://www.insp.mx/salud/index.html.

PMID- 14974279
TI  - [Risk factors and reproductive sequelae associated with Chlamydia trachomatis
      infection in infertile women].
AB  - OBJECTIVE: To assess the clinical and sexual lifestyle characteristics associated
      with Chlamydia trachomatis infection among women diagnosed with infertility.
      MATERIAL AND METHODS: Study subjects were women with an infertility diagnosis
      attending the infertility clinic at the National Institute of Perinatology.
      Endocervical specimens from 309 women were examined for Chlamydia trachomatis
      using the direct immunofluorescence method. Vaginal culture samples were taken
      before initiating treatment. The presence of other sexually-transmitted
      infections was also assessed. Demographic, sexual behavioral, historical, and
      clinical data were collected for each subject. RESULTS: Seventy-seven women
      (24.9%) were infected with C trachomatis. Of these women, 70 (90.9%) had only one
      sexual partner, 58 (75.3%) were married, and 19 (24.7%) were single or had a
      common-law sex partner. Intrauterine device (IUD) was the main contraceptive
      method used in 15 women (19.5%). A coinfection with other sexually-transmitted
      microorganisms was detected in 41 of these patients (53.2%). Nineteen (24.7%)
      women had undergone tubal ligation. Among women with C trachomatis infection,
      reproductive sequelae were found: 24 (31.2%) women had had abortions and 50
      (64.9%) had had a miscarriage. In 26 women cervical abnormalities were detected
      (33.8%); 50 (64.9%) had purulent vaginal discharge and 14 (18.1%) had pelvic
      pain. Bivariate analysis revealed that the risk factors for C trachomatis
      infection in women with infertility were: having a sex partner (OR = 2.96, 95% CI
      1.22-7.5, p = 0.008), common-law union (OR = 3.68, p = 0.03), and IUD use (OR =
      2.42, p = 0.01). CONCLUSIONS: A consistent relationship between C trachomatis
      infection and infertility was found. Infection with C trachomatis in women with
      infertility was associated with having one single sexual partner, marital status,
      and IUD use. The presence of ectropion and friability of the cervix may signal C
      trachomatis infection. Identification and presumptive therapy should be evaluated
      as measures to prevent and control C trachomatis infection in patients at risk.
      The English version of this paper is available
      at:http://www.insp.mx/salud/index.html.

PMID- 14974280
TI  - [Prevalence of anti-Chlamydia trachomatis and anti-Neisseria gonorrhoeae
      antibodies in Mexican populations].
AB  - OBJECTIVE: To estimate the prevalence of Chlamydia trachomatis (CT) and Neisseria
      gonorrhoeae (NG) infection in groups of individuals at different risks of
      sexually transmitted infections (STI). MATERIAL AND METHODS: Between January 1992
      and December 1993, a cross-sectional multicentric study was carried out at the
      Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (National
      Institute of Medical Sciences and Nutrition "Salvador Zubiran") in Mexico City.
      The study population consisted of 945 reproductive age subjects (585 females and
      360 males). Low and high risk groups were classified according to their risk for
      STI. High risk groups included infertile women with tubal damage, women with a
      history of ectopic pregnancy or abortion, infertile men, HIV/AIDS patients, homo-
      or bisexual men, and female commercial sex workers. Low risk groups included
      primigravidae, fertile men, and infertile women with no tubal damage. Serum anti
      NG and anti-CT IgG and IgA were determined, in duplicate by immune-enzymatic
      assay, using as antigens NG pili and the LI fraction of CT. Descriptive analysis
      is presented as percentages. RESULTS: NG prevalence in females was 13.7% by IgG
      and 14.3% by IgA. CT prevalence was 11.4% by IgG and 4.4% by IgA. In males, NG
      prevalences were 3.3% and 13.3% by IgG and IgA, respectively; CT prevalences were
      7.2% and 5.5%, respectively. In commercial sex workers, NG prevalences were 31.2%
      by IgG and 28.4% by IgA, and CT 25.0% and 5.7% by IgG and IgA, respectively. In
      women with infertility due to tubal damage the prevalences of NG were 5.6% and
      9.8%, respectively, and those of CT were 8.4% and 1.4%, respectively. In 110
      young primigravid NG prevalences were 4.5% and 10.0%, respectively, and CT 3.6%
      and 9.1%. CONCLUSIONS: These data confirm the high prevalence of Neisseria
      gonorrhoeae and Chlamydia trachomatis in female commercial sex workers and homo-
      or bisexual men, but not in other high-risk groups like infertile women or women
      with a history of ectopic pregnancy or abortion. The English version of this
      paper is available at:http://www.insp.mx/salud/index.html.

PMID- 14974281
TI  - [Seroprevalence of HBV, HCV, and HIV among blood donors in Irapuato, Mexico].
AB  - OBJECTIVE: To investigate the seroprevalence of viral markers for the human
      immunodeficiency virus (HIV), and the hepatitis B (HBV) and C (HCV) viruses, in
      blood donors at the General Hospital No. 2 Family Medicine Unit, of the Mexican
      Social Security Institute in Irapuato, Mexico. MATERIAL AND METHODS: A cross
      sectional descriptive study. Data was recorded on blood bank forms, and risk
      factors and illnesses were studied in the 7,056 blood donors at the General
      Hospital No. 2 Family Medicine Unit, of the Mexican Social Security Institute in
      Irapuato, Guanajuato, Mexico, over a period of two years (from July 1998 to June
      2000). A sample of 4,010 donors was obtained, each of whom underwent serological
      tests for HBV, HCV and HIV, serotypes 1 and 2, using an enzymatic immunoassay of
      third generation in serum or human plasma; seroprevalence rate of seropositive
      donors was calculated and stratified by age and sex. RESULTS: The combined
      seroprevalence for HBV, HCV and HIV was 2.5% (101); HCV was 1.14% (46), HBV,
      1.12% (45), and HIV, 0.24% (10). In males, HBV was 1.04% (33), HCV 1.07% (34),
      and HIV, 0.28% (9). In females, HBV was 1.42% (12), HCV was 1.42% (12), and HIV
      was 0.11% (1). Seropositive males had a 2.4 higher rate as compared to females.
      CONCLUSIONS: The seroprevalence of viral markers was greater than that reported
      in previous studies carried out in Mexico, which suggests that sexual
      transmission was the principal mechanism of infection; this reflects poor health
      education and the need to carefully select potential donors. The English version
      of this paper is available at:http://www.insp.mx/salud/index.html.

PMID- 14974282
TI  - [Etiology of cervical vaginal infection among patients of the Juarez Hospital of
      Mexico].
AB  - OBJECTIVE: To identify the etiologic agents of cervicovaginal infection in order
      to establish an accurate diagnosis and proper treatment. MATERIAL AND METHODS:
      From January 1995 to December 1999, bacteriological studies were done in cervical
      discharge specimens from 6,811 patients aged 13 to 65 years, seen at Hospital
      Juarez in Mexico City. All patients had leucorrhea, pruritus, hyperemia, and
      abdominal pain. Statistical significance was assessed using the chi-squared test.
      RESULTS: The frequencies of infectious agents were as follows: G. vaginalis,
      22.65%, Candida spp, 19.13%, C, albicans, 7.8%, T. vaginalis, 1.5%, Streptococcus
      group D, 11.78%, Streptococcus beta hemolytic, 4.59%, E. coli, 13.46%, and
      Klebsiella spp, 2.0%. Less frequent enterobacteria were: Citrobacter spp,
      Enterobacter spp, Pseudomonas spp, M. morganii, and P. mirabilis. Almost 3% of
      patients presented anaerobic species, which were always associated with G.
      vaginalis. Neisseria spp and N. weaveri were isolated in 0.15% each; N.
      gonorrhoeae was not isolated in any of the patients. Comparative data showed that
      Streptococcus beta hemolytic and E. coli increased markedly in the past two years
      (p < 0.001 for the latter). CONCLUSIONS: The diversity of etiologic agents
      requires performing bacteriological cultures of cervical and vaginal discharge to
      all symptomatic patients. The English version of this paper is available
      at:http://www.insp.mx/salud/index.html.

PMID- 14974283
TI  - Advances in diagnostic tests for bacterial STDs.
AB  - Because of their asymptomatic nature and nonspecific symptoms, laboratory tests
      are often required to diagnose a sexually transmitted infection. Over the past
      few years, there have been advances in technology, such as the development of
      nucleic acid amplification assays, which have improved our ability to diagnose
      infections caused by Chlamydia trachomatis. The finding that nucleic acid
      amplification tests can detect more infected individuals and are useful in
      screening low prevalence populations, has led to the development of strategies
      designed to reduce the cost of these assays without significantly impacting their
      sensitivity. The development of new tests for the diagnosis of syphilis has
      gained momentum from the report of a synthetic VDRL antigen, which will result in
      better nontreponemal antibody tests for syphilis. In spite of the completion of
      the genome sequence of Treponema pallidum and its annotation, we are still unable
      to cultivate this microorganism in vitro. However, the molecular revolution has
      resulted in the development of PCR assays for detecting Treponema pallidum in
      various types of clinical specimens, and to the production of recombinant
      antigens for use in tests that detect treponemal-specific antibodies. Further
      research will improve the availability of low cost, sensitive tests for the
      diagnosis of sexually transmitted infections. The English version of this paper
      is available too at:http://www.insp.mx/salud/index.html.

PMID- 14974284
TI  - [Experience with care of attempted suicide cases at a private hospital of Mexico
      City. The difficulty of diagnosing depression as risk factor of suicide].

PMID- 14974285
TI  - [The monkeypox virus appears in the American continent].

PMID- 14974286
TI  - [DDT/DDE concentrations and risk of hypospadias. Pilot case-control study].
AB  - OBJECTIVE: To evaluate the association between maternal serum DDT/DDE levels and
      risk of hypospadias. MATERIAL AND METHODS: A case-control study in Mexico City
      was conducted during 1997-1999 among 41 subjects with hypospadias and 28
      controls. Blood samples were obtained from study subjects. Information was
      obtained using a standardized questionnaire. Data were analyzed using
      multivariate logistic regression models. RESULTS: Maternal DDT and DDE levels
      showed no association with hypospadias (OR 1.13; 95% CI 0.24-5.29 and OR = 0.48;
      95% CI 0.15-1.60, respectively). Associated factors were older age of mothers (OR
      8.69; 95% CI 1.69-44.9), and working during pregnancy (OR 4.68; 95% CI 1.15
      18.9). CONCLUSIONS: Information about the endocrine effects of different levels
      of DDT/DDE in human subjects is scarce; dosage may be a determinant factor of the
      type of effect. The English version of this paper is available
      at:http://www.insp.mx/salud/index.html.

PMID- 14974287
TI  - [Ultraviolet radiation doses in Mexican students].
AB  - OBJECTIVE: To determine the ultraviolet radiation dose received by children and
      adolescents at elementary, middle, or high school. MATERIAL AND METHODS: A cohort
      study was conducted in the City of San Luis Potosi between May 2001 and April
      2002. The study population consisted of 80 school male and female children,
      selected at random, aged 6 to 19 years of age. The dose was quantitated during an
      entire schoolyear by recording the time each student was exposed to sunlight.
      Ultraviolet radiation was simultaneously monitored with terrestrial radiometry
      equipment. Holidays and weekends were excluded. Data were analyzed using
      univariate analysis and comparative analysis by sex and months of exposure. A
      regression model was fit to explain the dose of solar exposure. RESULTS: The
      erythemally weighted UV dose for Mexican schoolchildren averaged 16,456
      J/m2/year. Differences by gender were found: 14,264 J/m2/year in females vs.
      18,648 J/m2/year in males (Kolmogorov-Smirnov, p = 0.003). No significant
      differences were found among groups. Significant differences were found among
      months of exposure (Kruskal-Wallis, p = < 0.0001). Stepwise regression models
      were fit to find the best model, using generalized linear modeling and the Akaike
      information criterion, to explain the radiation dose according to month of
      exposure; the final equation was 587.20 + 438.45(gender)0.16(month)
      49.65(month2). The results showed higher radiation doses between March and
      September. CONCLUSIONS: A theoretical framework is advanced to formulate policies
      aimed at protecting children in Mexican schools from solar overexposure.
      Implementing prevention measures at least during the months of greatest exposure
      (March to June) is in order since 51% of the annual ultraviolet radiation dose is
      received in this period. By avoiding exposure 8 minutes daily, the radiation dose
      could be decreased in 39,495 J/m2, which is the dose accumulated in two years.
      The English version of this paper is available
      at:http://www.insp.mx/salud/index.html.

PMID- 14974288
TI  - [Prenatal care at the first level of care: characteristics of providers that
      affect users' satisfaction].
AB  - OBJECTIVE: To assess the satisfaction level attained by prenatal care users in
      primary health services in Mexico, and to compare the level of satisfaction
      according to characteristics of the provider and the service. MATERIAL AND
      METHODS: A cross-sectional survey was conducted to analyze data from 217 care
      provider-user pairs. Interviews were carried out in 95 primary care units in
      eight Mexican states. The information was collected through a) direct observation
      of the medical encounter, b) interviews with providers and users, and c) a
      questionnaire and knowledge examination to providers. Users' satisfaction was
      analyzed according to providers' clinical ability and the treatment received
      during the visit. Summary and dispersion measures of the main issues were
      calculated, as well as bivariate and trends analysis. RESULTS: User satisfaction
      in prenatal care is associated with the treatment received during the visit and
      to the waiting time before being attended, but not with the provider's clinical
      ability, nor with his or her age or gender. The treatment received during the
      visit was also associated with the user's socioeconomic level, where the poorer
      users received the worst treatment. CONCLUSIONS: Health services should assess
      users' satisfaction according with the type of medical encounter, particularly
      where resources are scarce and where economic disparities are present. In such
      cases, the provision of healthcare services may intensify inequality, with
      greater impact on the poorest. The English version of this paper is available
      at:http://www.insp.mx/salud/index.html.

PMID- 14974289
TI  - [Frequency of mycosis in immunosuppressed patients at a regional hospital of
      Mexico City].
AB  - OBJECTIVE: To isolate and identify the fungi in specimens collected from
      immunocompromised patients seen in Mexico City hospital, and to assess their
      association with mycosis. MATERIAL AND METHODS: A total of 268 specimens from 108
      patients were processed for mycological study, including direct examination,
      smears, cultures, and microcultures in specific media, in addition to biochemical
      tests. Most of the patients had been diagnosed with pulmonary tuberculosis and
      Acquired Immunodeficiency Syndrome (AIDS). RESULTS: One hundred and eighty-three
      yeasts and 66 mycelial fungi were isolated. Forty-five mycoses were diagnosed;
      the most frequent mycosis was pulmonary candidosis (32 cases). Candida albicans
      and C parapsilosis were the predominant species associated with mycotic
      infection. Five Cryptococcus neoformans var. neoformans, one C albidus, three
      Histoplasma capsulatum and one Geotrichum candidum isolates were associated with
      mycosis. CONCLUSIONS: Of the studied patients, 41.6% showed a mycotic infection,
      principally associated with AIDS and pulmonary tuberculosis. The English version
      of this paper is available at:http://www.insp.mx/salud/index.html.

PMID- 14974290
TI  - [Couples' knowledge and attitudes regarding the practice of family planning in
      the jungle of Peru].
AB  - OBJECTIVE: To assess the association of knowledge and attitudes about family
      planning (FP) with its practice in couples of the Peruvian jungle region.
      MATERIAL AND METHODS: A cross-sectional study was carried out in the jungle
      region in Peru (Pucallpa and Tarapoto), among 600 couples. Males were > or = 15
      years old and females between 15 and 49 years old, who had resided in the area
      for at least two years. A questionnaire was used to determine FP practices
      (defined as the use of modern contraceptive methods (MCM) for > or = 12 months),
      as well as attitudes and knowledge regarding FP. Frequencies were compared using
      the chi-squared test. Logistic regression was used to assess the association
      between demographic variables and MCM knowledge as well as MCM utilization. The
      association between sociodemographic variables and attitudes toward MCM was
      assessed with linear regression models. RESULTS: Males with primary education or
      with no formal education were twice as likely to have no knowledge about MCM
      compared with males with professional education (OR: 2.18, 95% CI: 1.05, 4.50).
      Females with a catholic partner were more likely to know about MCM than those
      whose partners did not practice any religion (OR: 0.60, 95% CI: 0.37, 0.97).
      Partner's lower education, older age of women, and rural background of males were
      all factors associated with a less favorable attitude toward FP practices.
      Couples in which the man did not know about contraceptive methods were more
      likely not to use MCM than couples where the man knew about MCM (OR: 1.57, 95%
      CI: 1.07, 2.30). Couples where the man had an intermediate level of acceptance
      towards FP were more likely not to use MCM than those where the man had a high
      level of acceptance (OR: 1.90, 95% CI: 1.03, 3.48). The strength of association
      was higher when the man had a low level of acceptance toward PF (OR: 2.23, 95%
      CI: 10, 4.51). CONCLUSIONS: Knowledge of contraceptive methods and attitudes
      toward FP among men are associated with the practice of FP by couples. Study
      findings show that male acceptance of MCM and FP is a necessary, important, and
      influential factor in FP promotion and practice. The English version of this
      paper is available at:http://www.insp.mx/salud/index.html.

PMID- 14974291
TI  - [Violence against women: knowledge and attitudes of the the medical staff at the
      Mexican Institute of Social Security, Morelos, Mexico].
AB  - OBJECTIVE: To asses the affective, cognitive, and behavioral attitudes of
      healthcare providers at the Mexican Institute of Social Security (MISS) in
      Morelos, Mexico; to identify the institutional and medical practice barriers that
      hinder screening and reference of battered women. MATERIAL AND METHODS: A cross
      sectional study was conducted between September and December 1999. A self
      administered questionnaire was applied to 269 general practitioners, specialists,
      and pre- and postdoctoral students working in 30 primary and secondary level of
      healthcare units in Morelos State. The data collection instrument was designed to
      assess healthcare providers' knowledge of and attitudes towards domestic violence
      during medical office visits. A knowledge index was constructed and analyzed
      using multivariate regression methods. RESULTS: Ninety percent of healthcare
      providers had never received training on violence against women. Healthcare
      providers' affective and cognitive attitudes after receiving training on the
      subject matter were more favorable compared to those with no training. Favorable
      attitudes were directly related to the number of training sessions. Most
      participants (63%) showed a moderate degree of knowledge on the subject, whereas
      21% were slightly knowledgeable and 16% were highly knowledgeable. Medical
      personnel with a moderate or high level of knowledge were 2.1 and 6 times more
      likely, respectively, to have favorable attitudes than those with a low degree of
      knowledge. Female physicians showed more favorable attitudes towards identifying
      and referring battered women. Medical personnel interested in further training on
      the subject of violence against women were 7.6 times more likely to show
      favorable attitudes than personnel not interested on the subject. CONCLUSIONS:
      Healthcare providers were not sufficiently able to assess and manage battered
      women. General and family practitioners were more interested in being trained, as
      compared with specialist physicians. Training on violence against women should be
      included in graduate medical, nursing, social service, psychology, and other
      public health areas. The English version of this paper is available
      at:http://www.insp.mx/salud/index.html.

PMID- 14974292
TI  - [Expenditure evaluation of the construction of health units: example of community
      participation].
AB  - OBJECTIVE: Demonstrate the economic benefits that community participation may
      render in the construction of health units. MATERIALS AND METHODS: The purpose of
      this study was to analyze the efficiency in the construction of 21 auxiliary
      health units and 81 rural health built through the Program to Support the
      Development of Health Services for the Non-Insured Population (PASSPA) through
      three different construction models (national public bidding, restricted
      invitation and community participation). Comparisons were also made with the
      units built through regular construction procedures of the Ministry of Health and
      other institutions. To evaluate the expenditure/m2, a univariate analysis using
      non-parametric statistics and a mathematical model of bootstrapping were used.
      RESULTS: The median expenditure/m2 and the delivery times for auxiliary health
      units, and the median expenditure/m2 for rural health units were smaller when
      using community participation. The expenditure/m2 of those units built through
      PASSPA was considerably lower than that of health units built through regular
      construction procedures. CONCLUSIONS: The use of community participation in the
      construction of auxiliary health units and rural health units may impact
      positively the resource investment and the delivery times when compared with
      units built through national public biddings and restricted invitations. The
      possibility of using community participation in other health activities
      (supervision, maintenance) should be evaluated. The English version of this paper
      is available at:http://www.insp.mx/salud/index.html.

PMID- 14974293
TI  - [Transvaginal bleeding in pregnancy, as risk factor of Rhesus-D antigen
      isoimmunization].
AB  - OBJECTIVE: The aim of the present study was to evaluate transvaginal bleeding
      (TVB) as a risk factor for Rhesus isoimmunization during pregnancy, in order to
      optimize the application of Anti-D gammaglobulin in non-immunized pregnant women,
      as an alternative to the routine application of Anti-D at 28 weeks of gestation.
      MATERIAL AND METHODS: This case-control study was conducted from 1995 to 2001 at
      Mexico's National Perinatology Institute. Cases (n = 24) were non-immunized
      pregnant women who showed positive anti-D antibody seroconversion during
      pregnancy or during the early puerperium. Controls (n = 24) were non-immunized
      pregnant women who enrolled after each case, with similar clinical
      characteristics but who had no anti-D antibody seroconversion during pregnancy.
      In all cases the newborns were Rh-positive. None of the patients received
      immunoprophylaxis at 28 weeks of gestation. The presence of TVB was recorded at
      any stage of pregnancy and before labor. Odds ratios with 95% confidence
      intervals were used to assess associations. RESULTS: TVB was observed in 18/24
      (75%) cases and in 5/24 (20%) controls. Preterm uterine contractions and
      threatened miscarriage were the most frequent causes of TVB. The presence of one
      TVB event during pregnancy increased 11.4 times (95% CI 2.9-44.0) the likelihood
      of Rhesus isoimmunization. TVB after 20 weeks of gestation increased the
      likelihood 5.0 times (95% CI 1.3-19.1). TVB before 20 weeks of gestation was not
      significantly associated with Rh isoimmunization (OR = 7.6, 95% CI 0.8-69.5).
      CONCLUSIONS: Prophylaxis with anti-D gammaglobulin should be given to all non
      immunized Rhesus-negative pregnant woman with TVB at any stage of pregnancy. The
      English version of this paper is available
      at:http://www.insp.mx/salud/index.html.

PMID- 14974294
TI  - [Physico-chemical signals involved in host localization and in the induction of
      mosquito bites].
AB  - Disease vector female mosquitoes respond to physic-chemical signals to localize
      vertebrate hosts for blood meals. Zoophylic mosquitoes preferentially respond to
      CO2 and octenol released in the breath and bodily fluids, while anthropophylic
      mosquitoes respond to lactic acid and a variety of sweat compounds. These
      compounds are modified by saprophytic microorganisms in the skin sebaceous
      glands. Other factors present in human dwellings contribute to the integration of
      microsystems with characteristic odors that have different attraction for
      mosquitoes, explaining the focalization of malaria transmission in few households
      in endemic areas. The identification of the chemical attractants and their
      molecular receptors could be used to complement new methods to attract mosquitoes
      to traps during epidemiological surveys, to increase their contact with
      insecticides in control interventions, and for genetic manipulation to divert
      mosquito bites towards other animal populations. The English version of this
      paper is available at:http://www.insp.mx/salud/index.html.

PMID- 14974295
TI  - [Accurate interpretation of point estimates, confidence intervals, and hypothesis
      contrasts in public health].
AB  - This essay reviews some statistical concepts frequently used in public health
      research that are commonly misinterpreted. These include point estimates,
      confidence intervals, and hypothesis tests. By comparing them using the classical
      and the Bayesian perspectives, their interpretation becomes clearer. The English
      version of this paper is available at:http://www.insp.mx/salud/index.html.

PMID- 14974296
TI  - [Statistics of hospital discharges of the National Health System public sector,
      2002].

PMID- 14974297
TI  - An ounce of prevention. The AHA tries to ward off political attacks by showing
      its worth through healthcare ROI study, election cards and a new logo.
AB  - Fearing political backlash, the American Hospital Association is taking the
      offensive, crafting an image that shows hospitals are providing essential
      services despite the hefty price tag. In an attempt to rebrand itself, the AHA is
      touting a study on healthcare return on investment, has created an election card
      detailing "Seven Steps to a Healthier America" and debuted a new logo.

PMID- 14974298
TI  - Sell, sell. Tenet escalates sell-off of hospitals as outlook for profits falls
      short of analysts' expectations.

PMID- 14974300
TI  - Healthcare is, isn't the issue.

PMID- 14974299
TI  - Dueling spending projections. OMB pins $534 billion price tag on Rx benefit.

PMID- 14974301
TI  - Cautiously quiet. Execs tight-lipped about Baxter shake-up.

PMID- 14974302
TI  - Disassociate from this plan. Pre-empting state regulation of insurance pools
      would hurt consumers.

PMID- 14974303
TI  - Connecting the dots. Verispan's annual 'IHN 100' ranks organizations that are
      using higher degrees of integration to excel clinically and financially.

PMID- 14974304
TI  - Back from the brink. Walter Becker specializes in helping rural, financially
      stressed hospitals regain their health.

PMID- 14974305
TI  - [Hypertension in young adults: indication for possible aortic coarctation].
AB  - Three adult patients, a woman aged 37 and two men aged 22 and 23 years
      respectively, were admitted due to an unexplained hypertension. After a
      significant delay, the diagnosis of aortic coarctation was established for these
      patients. In two of them the abnormality was operatively corrected and the blood
      pressure subsequently normalised; the third patient is on the waiting list for
      the operation. In all three patients an earlier diagnosis could have been
      established, had accurate blood-pressure measurements of both arms and at least
      one leg been performed. Late detection and treatment of aortic coarctation have a
      profound detrimental effect on survival. Therefore it is extremely important to
      accurately measure the blood pressure in the limbs of young patients with
      hypertension.

PMID- 14974306
TI  - ['New pathways to organ donation'; a recommendation of the Dutch Health Council].
AB  - Despite recent efforts at improvement, the current status of postmortem organ
      donation in the Netherlands is a reason for serious concern. The waiting lists
      for all organ transplantations are increasing in length. The Dutch Health Council
      was asked by the Minister of Health to report on any available alternative
      sources of donor organs, focusing especially on donation from living donors and
      postmortem donors in whom the heart is no longer beating. Kidney donation by
      living relatives is a well-known procedure that has been performed since 1950.
      Since HLA-matching is now less important due to new immunosuppressive regimens,
      transplants from unrelated living volunteers are also possible with good results.
      Live donation from emotionally involved persons should be encouraged. In case of
      ABO incompatibility, donors could be exchanged via the organ exchange
      institution. Live donation of liver segments by an adult to benefit a child
      recipient is justified. In case of an adult recipient this should be performed
      only under exceptional circumstances. Live donation of lung lobes and segments of
      intestine is still in a developmental phase. Postmortem donation of kidneys and
      livers from donors in whom the heart is no longer beating should also be
      encouraged. Donation of the lungs and pancreas from these donors is still an
      experimental procedure.

PMID- 14974307
TI  - [Fetal DNA in maternal blood].
AB  - There is a certain degree of foetal-maternal transfusion in every pregnancy. The
      possibilities for using intact foetal cells extracted from maternal blood for
      prenatal diagnosis are limited. Recently real-time polymerase chain reaction
      (PCR) techniques have allowed the identification and quantification of foetal DNA
      in the maternal blood. Foetal sex determination with Y-chromosome-PCR has been
      found to have a specificity of 100%. The sensitivity is 96% but increases with
      gestational age, so that from 10 weeks onwards the sensitivity approaches 100%.
      In the case of X-linked diseases, this technique can reduce invasive prenatal
      diagnosis by 50%. In the case of a foetus with an elevated risk for congenital
      adrenal hyperplasia, early non-invasive foetal sexing can also shorten the period
      of maternal dexamethasone use so as to prevent virilisation in the female foetus.
      Early second trimester non-invasive foetal RhD genotyping with an RhD-PCR has a
      sensitivity and specificity of 100% each. Therefore in the future, anti-D
      immunoprophylaxis will be superfluous in RhD-negative women with an RhD-negative
      foetus. Theoretically all new and paternal inherited disorders with a known gene
      defect can be detected in maternal plasma. Some examples have already been
      described. Recently published small scale studies describe elevated
      concentrations of free foetal DNA in maternal plasma in (threatening) preterm
      labour, pre-eclampsia and aneuploidy. Large-scale studies are necessary to
      demonstrate the value of these findings.

PMID- 14974308
TI  - [Gallstones following considerable weight loss and recommendations for their
      prevention].
AB  - Obesity is an increasing public health problem. As a consequence, many people
      attempt to lose weight by dieting or participation in weight loss programmes.
      Weight loss is associated with an increased risk of symptomatic gallstones.
      Preventive measures include keeping the rate of weight loss below 1.5 kg per
      week, and providing a fat intake of at least 7 g a day. If it is expected that
      the rate of weight loss will be faster or difficult to control, for example after
      bariatric surgery, prophylaxis with ursodeoxycholic acid may be considered.

PMID- 14974309
TI  - [Diagnostic image (173). A pregnant woman with an abnormal position of the fetus.
      Intra-abdominal pregnancy presenting as a abnormal fetal position].
AB  - A 42-year-old pregnant Namibian woman presented with an abnormal position of the
      foetus due to intra-abdominal pregnancy.

PMID- 14974310
TI  - [From gene to disease; spastin and hereditary spastic paraparesis].
AB  - Hereditary spastic paraparesis (HSP) belongs to a group of genetically and
      clinically heterogeneous disorders characterised by progressive spasticity of the
      legs and hyperreflexia. A further clinical distinction is drawn between pure and
      complicated HSP depending on the presence of other neurological and non
      neurological signs. HSP may be inherited either as autosomal dominant, recessive,
      or X-linked. Twenty-two loci have been identified and additional ones are
      envisaged. In autosomal dominant HSP, 11 loci (five genes) have been identified,
      the most prevalent of which is linked to chromosome 2p, coding for spastin, an
      ATPase belonging to the AAA family (acronym of 'ATPase associated with diverse
      cellular activities'). Spastin is a nuclear protein, present in neurons, but not
      in glial cells, and seems to be involved in microtubule dynamics. Nonsense and
      frameshift mutations result in a reduced amount of spastin.

PMID- 14974311
TI  - [Colonic lavage prior to colonoscopy: comparable outcomes of two polyethylene
      glycol preparations and a sodium-phosphate solution].
AB  - OBJECTIVE: Comparison of three cleansing solutions for bowel preparation prior to
      colonoscopy. DESIGN: Prospective, randomized. METHOD: 140 outpatients referred
      for colonoscopy were randomized into three groups for cleansing with 4 litres PEG
      4000, 4 litres PEG 3350 or with 90 ml sodium phosphate with an additional 2.5
      litres of fluid. Between cleansing and colonoscopy, patients filled in a
      questionnaire concerning taste, abdominal cramps and tolerance to the procedure.
      Blinded to the type of cleansing the endoscopist scored the effects on the colon
      and rectosigmoid, and made the endoscopic diagnosis. RESULTS: All data were
      available for 127 of the 140 patients (50 men, 77 women), mean age 51 years
      (range 18-96). Comparison between the three groups showed no statistically
      significant difference in the opinion of the patients concerning taste, abdominal
      cramps and tolerance of lavage. The endoscopist's scoring of total colon
      cleansing showed a small reduction in colon cleanliness when using sodium
      phosphate compared to PEG 3350 (p = 0.03). No differences were found between the
      two PEG solutions. Combining both PEG solutions and comparing them with the
      sodium-phosphate solution showed fewer abdominal cramps (p = 0.07) with sodium
      phosphate and a cleaner colon with PEG (p = 0.07). Women complained slightly more
      of abdominal cramps and were slightly less tolerant of the procedure than men.
      Previous colonic surgery did not influence the results. Patients with diverticula
      were older, but no other effect of cleansing was found. CONCLUSION: The three
      preparations are comparable in their cleansing effect and tolerance by the
      patient.

PMID- 14974313
TI  - [Symptoms of cholelithiasis following cholecystectomy; possibly a second
      gallbladder].
AB  - Three patients with cholelithiasis were found to possess a duplicate gallbladder.
      A 48-year-old woman continued to have symptoms one year after cholecystectomy, a
      69-year-old woman had symptoms even though her gallbladder had been removed 40
      years before, and in a 29-year-old woman a second gallbladder was found during
      cholecystectomy. In all three patients, the second gallbladder was removed as
      well, after which they recovered. The differential diagnosis of persistent
      symptoms following cholecystectomy should also consider the possible presence of
      an accessory gallbladder.

PMID- 14974312
TI  - [Reasons why patients do or do not participate in clinical trials; a systemic
      review of the literature].
AB  - OBJECTIVE: To assess the factors that may influence a patient's consent to
      participate in a clinical trial. DESIGN: Systematic literature survey. METHOD:
      Studies on the characteristics of patients, trials, the physicians requesting
      informed consent and the informed consent procedures were looked for in Medline,
      Embase, and Cinahl. Articles published in English, German, Dutch or French in the
      period 1980-2002 and originating in Europe, the United States, Canada, New
      Zealand or Australia were included. Studies on non-adults, healthy experimental
      subjects or less than 30 patients were excluded. RESULTS: Thirty suitable studies
      were retrieved. Factors that may affect the granting of consent to participate in
      a clinical trial included: uncertainty of the patient, randomisation and the use
      of a placebo, the relationship between the person asking for informed consent and
      the patient, and the dissemination of information during the informed consent
      procedure. Since these factors are often interrelated, no single factor could be
      identified as decisive for participation in a clinical trial; they can influence
      the decision of the patient to participate in a trial in either a positive or a
      negative direction. CONCLUSION: Optimalization of the information concerning
      informed consent, the way the information is provided and the attitude of the
      person requesting informed consent are important and sometimes decisive factors
      that may determine the participation process.

PMID- 14974314
TI  - [Integration of training in pharmacology and pharmacotherapy in the medical
      curriculum in Leiden, the Netherlands].
AB  - In the new medical curriculum at Leiden University Medical Centre, the
      Netherlands, two aspects of the training in pharmacology and pharmacotherapy--the
      acquisition of knowledge and its application--have been integrated. On the basis
      of the approved subject matter and goals, four computer programmes were
      developed: the Teaching Resource Centre (TRC) Pharmacology database, the
      interactive TRC teaching programme, the Individual Therapy: Evaluation and Plan
      (ITEP), and the relational curriculum database. Together, these programmes
      provide the necessary knowledge in pharmacodynamics and pharmacokinetics,
      pharmacotherapy and the mechanisms of drug action, as well as possibilities for
      monitoring the educational process. The figures are created with the aid of a
      symbolic language, assuring a uniform presentation of all the information
      throughout the curriculum. Attention is also paid to the integration of these
      aspects with other subjects in the medical curriculum. Implementation of the
      teaching system in pharmacology was started at the beginning of 2001. Currently,
      the TRC database contains almost all the subject matter that is planned to be
      included. The next step in the process will be the assessment of both the
      knowledge and its application. TRC Pharmacology is a new method of integrating
      basic knowledge of pharmacology and pharmacotherapy in a medical school
      curriculum.

PMID- 14974315
TI  - [The 'Inguinal Hernia' guideline of the Association of Surgeons of the
      Netherlands].

PMID- 14974316
TI  - [Bilateral swelling of the parotid glands as part of a systemic disease].

PMID- 14974317
TI  - [Intracystic carcinoma of the breast: diagnosis and treatment in retrospective
      investigation and published literature].

PMID- 14974318
TI  - [When the physician's calling demands special fearlessness. Doctor Courage].

PMID- 14974319
TI  - [Migraine, inflammation, genes. New risk factors for stroke].

PMID- 14974320
TI  - [New prevention program in obesity. When one becomes mobile then the pounds
      tumble, too].

PMID- 14974321
TI  - [Great topical mix in the MMW, but please do not set physicians against each
      other!].

PMID- 14974322
TI  - [Aortic valve replacement in patients older than 70. Is the effort justified?].

PMID- 14974323
TI  - [Diagnosis and therapy of aortic stenosis in older age. When does it become
      critical?].
AB  - Together with mitral valve insufficiency, aortic stenosis is the most common
      heart defect in adulthood. The two major forms are degenerative senile aortic
      stenosis of old age, and secondary degenerated bicuspid valve manifesting in
      middle age. A typical feature is a lengthy asymptomatic course due to
      compensating ventricular hypertrophy with a constant systolic wall tension. With
      the aid of Doppler echocardiography aortic stenosis can be accurately quantified.
      Although effective drug treatment is not available, evidence is mounting that
      statins are capable of slowing the progression of valvular sclerosis, presumably
      on the basis of pleiotropic, anti-inflammatory effects. As a rule, the onset of
      symptoms (dyspnea, angina, syncope) is an indication for surgery. As a result of
      rising life expectancy, the proportion of elderly and very old patients with
      degenerative senile aortic stenosis is increasing appreciably, and presents a
      challenge in terms of deciding appropriate individual therapy. Advances in
      valvular surgery in high old age, however, can offer many of these patients the
      option of a procedure with an acceptably low risk and longer-term prognostic and
      symptomatic benefits following successful surgery.

PMID- 14974324
TI  - [Surgical treatment of aortic valve disease in old age].
AB  - In terms of long-term survival and quality of life, excellent results with aortic
      valve replacement (AVR) can also be achieved in patients older than 70 years of
      age. An indication for this procedure is given in symptomatic patients with
      significant aortic valve stenosis, patients with severe acute aortic
      insufficiency (AI), those with signs of cardiac insufficiency but still normal
      left ventricular function, and asymptomatic AI patients with an ejection fraction
      of less than 50% and/or an end-diastolic LV diameter (EDD) of more than 75 mm or
      an end-systolic diameter (ESD) of more than 55 mm. Many patients with a heart
      defect in need of surgical treatment also have CAD as well, in which case a
      bypass should be performed at the same time. For AVR, both mechanical and
      biological prostheses are available, the latter being regarded as the method of
      choice in patients aged over 70. The mechanical variant requires life-long
      anticoagulation therapy with phenprocoumon.

PMID- 14974325
TI  - [Treating acne: avoid the development of antibiotic resistance by applying
      topical and combined therapy].

PMID- 14974326
TI  - [Difficult differential diagnosis. Chronic pseudo-erosive lesion of the
      foreskin].

PMID- 14974327
TI  - [What did the ALLHAT study bring? To do the one without foregoing the other].

PMID- 14974328
TI  - [Proven in the practice. Follow up of the use confirms high trial value].

PMID- 14974329
TI  - [First comparison of 2 statins shows: only radical LDL lowering stops coronary
      atherosclerosis].

PMID- 14974330
TI  - [The proton pump especially steady in grip. Fast help for nightly reflux
      complaints].

PMID- 14974331
TI  - [Vascular patient with high infarction risk. Does the AT-1 blocker protect as
      well as an ACE inhibitor?].

PMID- 14974332
TI  - [New antiviral agent. Hepatitis B therapy with slight resistance risk].

PMID- 14974333
TI  - [Microcirculation in peripheral arterial occlusive diseases will improve.
      Prostaglandin can prevent surgery].

PMID- 14974334
TI  - [Beta blocker improves the endothelial function. Gas-forming blood vessel
      protection].

PMID- 14974335
TI  - [Humidity and winter temperatures make the pain patient suffer. When the cold
      front affects the joints].

PMID- 14974336
TI  - [How does it function? Abdominal duplex ultrasonography].

PMID- 14974337
TI  - [Continuation 50. Type 2 diabetes: possibilities and limitations of
      pharmacological therapy].

PMID- 14974338
TI  - [Coronary surgery in patients over 65 year of age].
AB  - The aim of the study was to analyze the risk and operative results in bypassed
      patients with ischemic heart disease (IHD) older than 65 years. MATERIAL: The
      study group was 117 patients over 65 years old (66-87, mean 71 years) and the
      controls were 233 patients below 65 years old (31-64, mean 51 years), who
      underwent coronary artery grafting. METHODS: The frequency of such risk factors
      as diabetes, smoking, hypertension and IHD and myocardial infarction (MI) family
      history were performed. Theoretical operative risk in study group and in control
      group were estimated using: Parsonnette, The Cleveland Clinic Foundation and Euro
      Score scales. The number of anastomoses, the frequency of using the internal
      mammary artery (IMA) graft to left anterior descending (LAD) coronary artery and
      perfusion, aorta clamping and repercussion times were compared in both groups.
      The operative mortality, Q wave MI and stroke were analysed in study and control
      groups as the operative results. RESULTS: There was the higher percent of women
      and patient with hypertension and lower percent of smokers in the study group.
      The total cholesterol, HDL-cholesterol, LDL-cholesterol, PAI-1, fibrinogen,
      creatinine levels and the number of the patients with cerebral or peripheral
      atherosclerosis were similar in both groups. The triglycerides level was higher
      in the study group. In the study group the use of IMA, as the conduit was lower.
      There was no difference in the perfusion time, aorta clamping time and
      reperfusion time. An operative mortality was higher in the older group (8.5% vs
      2.6%; p < 0.05). The perioperative Q wave MI rate was 7.7% and 4.3% (ns) and
      stroke rate was 3.4% and 2.6% (ns). Estimated in our patients, theoretical
      operative mortality in the study group was 6.5-8.7% and in the control group was
      2.1-2.7%, and there was no statistical differences compare to real operative
      mortality. The most adequate to real mortality was theoretical mortality
      estimated using EuroScore scale. CONCLUSIONS: 1. Coronary bypass surgery
      mortality was higher in the patients over 65 years old and the myocardial
      infarction was the main reason of death. 2. Using operative risk scales, the
      prognosis individual operative risk mortality to every patient can be estimated
      and if this risk is too high it is possible to eliminate some risk factors or
      desist from operative treatment.

PMID- 14974339
TI  - [Safety and efficacy of ANGIOGUARD protection device for the prevention of distal
      embolization during PCI in patients with unstable angina].
AB  - The use of IIbIIIa receptor blockers decreases the number of major ischemic
      adverse cardiac events during PCI. However, microinfarcts (post procedural CK-MB
      elevations) still occur despite optimal antithrombotic treatment. In patients
      (pts) with increased risk of atheroembolization during PCI the use of additional
      mechanical protection of embolization can be considered. The purpose of the study
      was to determine safety and efficacy of additional use of first generation
      coronary filter (Angioguard) to prevent microembolization during PCI in pts with
      unstable angina (UA). METHODS: 31 pts with UA (Braunwald IIB, IIIB) undergoing
      urgent PCI were randomized in the catheterization laboratory for additional use
      of Angioguard coronary filter or not (placebo). All pts were treated with
      aspirin, ticlopidine (500 mg/d), heparin (60 U/kg, ACT 200-300 sec.) and
      eptifibatide (bolus 2 x 180 micrograms/kg i.v. and 2 micrograms/kg/min. infusion
      for 18-24 h). We analyzed the extent of microembolization (serial CK-MB),
      presence of embolic material in the device after procedure, technical problems.
      Major cardiac events (death, myocardial infarction (MI), urgent target vessel
      revascularization (TVR)) were also considered. RESULTS: PCI was successful in all
      pts. There was no death, Q wave MI or urgent TVR. Angioguard was successfully
      installed in 100% pts; however balloon predilatation was necessary in 9 (60%)
      pts. In 9 pts (60%) there was no possibility to prevent embolization oflarge side
      branches that originated close to the culprit lesion. Presence of embolic
      material in the filter was confirmed in microscopic analysis of each device.
      However CK-MB level was elevated in 4 pts (29%) in Angioguard group comparing to
      0% in control group without protection device. CONCLUSION: First generation
      Angioguard protection device do not successfully prevent distal embolisation
      during PCI in pts with UA and its use is associated with many technical problems.

PMID- 14974340
TI  - [Improvement of coronary flow reserve during intravascular ultrasound guided
      percutaneous coronary intervention (PCI)].
AB  - Experience with intravascular ultrasound (IVUS) and physiological methods for
      measuring coronary flow reserve during percutaneous coronary interventions (PCI)
      has shown that quantitative coronary angiography (QCA) is far from ideal to
      evaluate immediate efficacy of PCI. Balloon angioplasty under IVUS guidance
      allows for safe use of larger balloon catheters than estimated by QCA and
      provides long-term outcomes similar to stenting. The aim of the present study was
      to evaluate the effect of percutaneous balloon angioplasty guided by IVUS on
      postprocedural coronary flow reserve. The study population included 21 patients
      undergoing percutaneous transluminal coronary angioplasty using balloon catheters
      sized according to the angiographic reference segment diameter, in whom residual
      stenosis did not exceed 35% and there was no vascular wall dissection requiring
      stenting. CFR was measured at baseline, after dilatation with QCA sized balloons
      and after IVUS guided intervention. As compared with angio-graphically guided
      balloon angio-plasty, PTCA with IVUS guidance resulted in a significantly
      increased CFR relative to its baseline value. The present findings suggest that
      impaired coronary flow reserve after angiographically guided PCI may be a result
      of non-optimal vessel dilatation due to limitations of quantitative coronary
      angiography in balloon sizing. PCI with IVUS guidance allows for improvement of
      CFR as compared with conventional balloon angioplasty.

PMID- 14974341
TI  - [Knowledge of hypertension and blood pressure measurement procedure among
      students of last year of medical school in Cracow].
AB  - The knowledge about hypertension--especially its diagnosis and therapy--among
      graduates of medical schools, is very important in view of hypertensive
      epidemics. The aim of this study was to assess the medical graduate's knowledge
      about recommended technique of blood pressure (BP) measurements, the factors
      affecting BP measurement value, the WHO/ISH--1999 hypertension diagnostic
      criteria, and its complications and basic therapy rules. The questionnaire
      investigating the respondent's knowledge was filled out by 132 medical students
      of the 6th year Medical College of the Jagiellonian University, in Cracow, from
      February till June 2000. Only 21.2% of students had good knowledge about BP
      measurement technique, 70% to 90% of subjects knew hypertension diagnostic
      criteria, about 30% gave the correct values defined as "high-normal". About 37.1%
      were aware of complications concerning heart, brain, kidney, eye and peripheral
      blood vessels. Only 11% knew all drugs recommended by WHO/ISH guidelines, as
      first-line medication; but 95% were only able to mention at least four of them
      (diuretics, beta-blockers, ACE-I, Ca-blockers). The students have unsatisfactory
      levels of knowledge about hypertension. This indicates poor preparation of future
      physicians in treatment of hypertensive problems.

PMID- 14974342
TI  - [First ischemic stroke in the very old: etiology, clinical course and outcome].
AB  - This study was designed to investigate the prevalence of risk factors, etiology,
      clinical course and outcome of the first-ever ischemic stroke in patients aged at
      least 85 when compared with younger patients with ischemic stroke. We studied 802
      patients with first-ever ischemic stroke, including 103 patients at the age of 85
      and more, and 699 patients at the age of 60-84. We collected data regarding the
      prevalence of risk factors, etiology of stroke, severity of neurological deficit
      and the presence of consciousness disturbances. The major complications were
      registered and the infarction volume was assessed using computed tomography.
      Mortality and functional status of the survivors were assessed on the 30th and
      90th day after stroke using Barthel Index. Very old patients with ischemic stroke
      were characterized by greater percentage of women and higher frequency of
      ischemic heart disease; diabetes, obesity and smoking were all noted less
      frequently in this group. Very elderly subjects presented more frequently with
      TACI syndrome (24.3% and 14.6%, respectively; p < 0.05). They had greater
      neurological deficit in all days of assessment and were more likely to have the
      consciousness disorders on admission (39% and 22.3%, respectively; p < 0.001).
      Urinary tract infection was the only major complication more frequently seen in
      very old subjects (53.4% and 35.3%, respectively; p < 0.05). The studied groups
      did not differ regarding etiology of stroke, the length of hospital stay and the
      incidence of other complications. 30th and 90th-day mortality was greater among
      very elderly subjects (28.1% vs 16.4% and 46.6% vs 24.6%, respectively; both p <
      0.05). The disability assessed 30 and 90 days after stroke was also much greater
      in very old patients. Very old patients with first ischemic stroke have greater
      neurological deficit, worse functional status and greater mortality after stroke.
      They are more likely to have ischemic heart disease and less likely to have
      diabetes or obesity. The causes of stroke, incidence of complications (with the
      exception of urinary tact infections), size of the lesion and length of hospital
      stay are similar in very old and younger patients with stroke.

PMID- 14974343
TI  - [Percutaneous closure of patent foramen ovale: prevention of recurrent strokes.
      Immediate results and one year follow-up].
AB  - Patent foramen ovale (PFO) is a risk factor for transient ischemic attack (TIA)
      or ischemic stroke. In this study we investigated short and long-term safety and
      efficacy of percutaneous closure of PFO in secondary stroke prevention. METHODS
      AND RESULTS: We implanted PFO-closure devices in 8 patients (3 men and 5 women)
      after TIA or ischemic stroke (mean age 38 +/- 15.2). The implantation procedures
      were performed in general anesthesia, under transoesophageal echocardiography and
      fluoroscopy. No periprocedural complications were observed. Post-procedural
      shunts were not observed either. All patients did not experience any TIA or
      stroke during follow-up (5 patients completed a 1-year period). Only in one
      patient transient ventricular extrasystolia was observed 1 month after device
      implantation. CONCLUSIONS: Percutaneous PFO closure seems to be a safe and
      effective technique in prevention of recurrent stroke.

PMID- 14974344
TI  - Calpain 10 gene polymorphisms and the risk of ischaemic stroke in a Polish
      population.
AB  - Experimental studies showed that calpain inhibitors suppressed post-ischaemic
      changes in the brain. We examined whether an association exists between variants
      of three single nucleotide polymorphisms (SNPs) -43, -19, and -63 in the calpain
      10 gene and either stroke or size of ischaemic lesions on the CT in a Polish
      population. We included 209 patients with a first ischaemic stroke and 148
      controls. The patients were divided into four groups based on the infarct size
      assessed on the CT taken within two week after stroke. Alleles of SNP19 were
      determined by electrophoresis of the PCR product on agarose gel by size; while
      for SNP43 and -63 the RFLP method was used. The allele frequencies for patients
      and controls were similar in both groups: SNP43- G/A- 73.5%/26.5% vs. 71.0%/29%,
      SNP19-three 32 bp/two 32 bp repeats--65.7%/34.2% vs. 62.2%/37.7%; SNP63- C/T-
      89.5%/10.5% vs. 90.9%/9.1%, respectively. The distribution of the genotypes,
      haplotypes, and haplotype combinations did not differ in both groups. The
      distribution in the subgroups of patients based on the size of the ischaemic
      lesions was similar to controls. Our study did not showed any association between
      calpain 10 SNPs: -43, -19, and -63 and ischaemic stroke, or with the size of post
      ischaemic cerebral lesions in a Polish population.

PMID- 14974345
TI  - [Stroke prevention: carotid stenting or carotid endarterectomy?].
AB  - Carotid angioplasty and stenting (CAS) has been introduced as an alternative to
      carotid endarterectomy (CEA) for treatment of carotid atherosclerosis. This paper
      summarizes benefits and limitations of CAS and CEA, describes the main technical
      points of CAS procedure, use of protection devices and adjunctive pharmacotherapy
      to reduce procedure related incidents.

PMID- 14974346
TI  - [Is homocysteine a new factor in the pathogenesis of restenosis after
      percutaneous coronary angioplasty?].
AB  - Restenosis after coronary angioplasty is still a significant problem despite the
      dynamic development of intervention cardiology. Homocysteine causes endothelial
      dysfunction and disorders of the coagulation system, increases in platelets
      aggregation and stimulates the proliferation of the vascular smooth cell. These
      were the reasons for investigating the relation between homocysteine level and
      the risk of restenosis. Some studies indicate that higher homocysteine levels
      increase the risk of restenosis after coronary angioplasty, while it has not been
      proven in other studies. The results of the only one randomized trial
      demonstrated that pharmacological lowering of the homocysteine level decreased
      the risk of restenosis after coronary angioplasty. At this time there are some
      studies which started focusing on the role of lowering homocysteine level in
      cardiovascular risk. These investigations may explain the importance of
      homocysteine level in the development of cardiovascular diseases. There is a need
      of a large prospective multicenter trial assessing the relationship between
      increased homocysteine level and the frequency of restenosis after coronary
      angioplasty. Using intravascular ultrasonography could be especially helpful in
      assessing the role of decreasing homocysteine level on neo-intima formation and
      arterial remodeling after intervention.

PMID- 14974347
TI  - [Erythropoietin administration in diabetic patients].
AB  - This paper presents the role of erythropoietin application in diabetic patients
      with accompanying renal failure. The main cause of anemia in diabetics are:
      nephropathy, structural lesions of erythrocyte membrane and blood loss connected
      with diagnostic and therapeutic actions. There are publications which demonstrate
      that in patients with diabetes type 1 or 2 with accompanying nephropathy, anemia
      appears more frequently than in the group of patients with chronic renal failure
      caused by other factors. It is supposed, that the impaired erythropoietin
      synthesis in diabetics can be caused by autonomic neuropathy. Erythropoietin
      administration in case of diabetic nephropathy has a beneficial influence on fat
      metabolism, immune response and reduction of insuline resistance. Erythropoietin
      because of reduction of vascular endothelial growth factor synthesis blocks the
      development of diabetic retinopathy and macroangiopathy. Erythropoietin reduces
      the risk of the left-ventricular hypertrophy caused by anemia. Very important is
      that the erythropoietin resistance is lower in diabetics. Scientists who are
      adverse to erythropoietin administration in patients with diabetic nephropathy
      maintain, that it can lead to vascular complications and the deterioration of
      glycemia control.

PMID- 14974348
TI  - [New antiretroviral medications in therapy of HIV infections].
AB  - Therapeutic options continue to expand with the development of new drugs and new
      strategies for using them. This report describes progress in laboratory and
      clinical trials of new inhibitors of reverse transcriptase and viral protease,
      turning special attention on their efficacy for therapy of patient with drug
      resistant viruses for current therapies. The second group is a new class of anti
      HIV drugs called "fusion inhibitors" or "viral entry inhibitors" The fusion
      inhibitors halt HIV at a unique point in the virus life cycle blocking attachment
      of virus to the membrane of target cells. All of the described drugs are not
      potent enough to eradicate the virus. Diminished toxicity of proposed new
      antiretroviral substances, more tolerable regimens easier for patients and
      efficacy against resistant viruses to currently used drugs are giving hope for
      further prolongation of life of HIV infected patients.

PMID- 14974349
TI  - [Multiple myeloma: the role of angiogenesis and therapeutic application of
      thalidomide].
AB  - This article contains biological, epidemiological and clinical data on multiple
      myeloma and the role of proangiogenetic cytokines in the development of this
      neoplasm. The role of angiogenesis in the transformation and development of
      multiple myeloma is a topic which is presently readily studied in leading
      scientific centres in many parts of the world. Serum and bone marrow levels of
      cytokines such as VEGF, b-FGF, IL-6, sIL-6R, HGFare raised in patients with
      multiple myeloma as compared to healthy subjects; their values correlate with the
      severity of disease and are presently recognised as prognostic factors.
      Thalidomide has anti-inflammatory, immuno-modulating and antiangiogeneic
      properties but the mechanism of its action is not yet completely understood.
      Thalidomide is presently used in therapy of patients with resistant and relapsed
      multiple myeloma with very promising results.

PMID- 14974350
TI  - Takeout nation.

PMID- 14974351
TI  - A family's tangled ties.

PMID- 14974352
TI  - Hope sprouts eternal.

PMID- 14974353
TI  - Avian influenza A(H5N1).

PMID- 14974354
TI  - Recommendations from the Strategic Advisory Group of Experts to the Department of
      Immunization, Vaccines and Biologicals.

PMID- 14974355
TI  - KT/V: the denominator dilemma.
AB  - The efficacy of solute removal by renal replacement therapy can be assessed by
      the commonly used index of KT/V. However, KT/V has a different meaning in
      hemodialysis (HD) and peritoneal dialysis (PD), and KT/V in HD and PD can
      therefore not be compared. For example, in HD one uses an instantaneous clearance
      K = (solute removal rate)/CB, where CB is solute concentration in blood. Thus, K
      is the clearance of the purification device (hemodialyzer) and in continuous
      ambulatory peritoneal dialysis (CAPD) it is the diffusive mass transport
      parameter (KBD, MTAC) but this is not used in clinical practice. Instead, in CAPD
      one uses a treatment clearance KT = (average rate of solute removal per
      treatment)/CBO, where CBO is CB at the beginning of the treatment. Whereas K is
      constant, KT decreases during the CAPD dwell. The current practice of using KTT/V
      for CAPD but KT/V for HD leads to confusion. Furthermore, T is different in CAPD
      (about 150 hours per week) and HD (about 12 hours per week). Finally, V, the
      distribution volume of the solute (usually urea), is calculated in different ways
      in HD and PD. V is strongly related to nutritional status and as such it is a
      strong predictor of survival. KT in HD, and KTT in CAPD, represents the dialysis
      dose and as such also a predictor of survival. This may at least in part explain
      why the recent Ademex study in PD patients and the Hemo study in HD patients
      could not demonstrate any strong impact of different levels of KT/V (KTT/V) on
      clinical outcome. In this review, we discuss the shortcomings of the "KT/V"
      concept, in particular its limited value for comparisons between dialysis
      efficiency in PD and HD, as well as the dilemma of using V as the denominator
      considering that V in itself may represent a strong predictor of outcome.

PMID- 14974356
TI  - Mathematical models of fluid and solute transport in peritoneal dialysis.
AB  - Three types of mathematical models of peritoneal transport are reviewed:
      distributed models, membrane models, and pore models. The distributed model
      described the capillary bed distributed within the tissue with two sets of
      transport parameters for the capillary wall and for the tissue separately. The
      membrane and the three pore models consider blood as a compartment separated by a
      transport barrier from the dialysis fluid in the peritoneal cavity. The membrane
      model describes the barrier using "black box" transport parameters, whereas the
      three pore model assumes three types of pores across the barrier (large, small,
      and ultra small pores) and a mathematical theory of fluid and solute transport
      through the pore. Each model contributes its specific share to investigations of
      peritoneal transport. The basic features and specific areas of application of all
      three types of the models are discussed.

PMID- 14974357
TI  - Efficacy of automated peritoneal dialysis: from minimum to optimum.
AB  - The aim of the study was assessment of theoretical possibilities of the Automated
      Peritoneal Dialysis (APD) optimization. The analysis of influence of dwells
      number modification and peritoneal transport character on Nightly Intermittent
      Peritoneal Dialysis (NIPD) efficacy and adequacy was performed. In the study the
      alternative method of theoretical foreseeing of peritoneal dialysis efficacy and
      adequacy was applied. This method was based on direct measurement of the velocity
      of solute peritoneal transport (SMTR). On the basis of SMTR, the dialysis
      efficacy expressed as total dialysed urea and dialysis adequacy expressed as Kt/V
      were estimated. The values of listed parameters were calculated for the different
      NIPD schedules (4-9 dwells during 8-hours session). It was revealed that the
      shortening of dwell time with simultaneous multiplying of dwell numbers resulted
      in increase of dialysis efficacy and adequacy. However, this improvement was non
      proportional to the increase of dialysis solution volume and it did not provide
      the optimum of dialysis nor recommended level of adequacy even during the session
      consisting of 9 dwells. There were no statistically significant differences of
      Kt/V values between subgroups of patients with different character of peritoneal
      transport assessed according to PET test. The tendency to achieve the recommended
      values of Kt/V was observed in high transporters group. The results of the study
      indicate the large capabilities of APD optimization. The direct measurement of
      peritoneal transport velocity allows to provide better individualization of PD
      program. The prediction of APD efficacy and adequacy on the base of presented
      method seams to be an interesting alternative.

PMID- 14974358
TI  - [Pathomechanism of hyperlipoproteinemia in chronic renal failure].
AB  - Lipid disorders are one of the known metabolic changes associated with chronic
      renal failure (CRF) [1, 2]. They are present as: hypertriglyceridemia--existed in
      60% of CRF patients and hypercholesterolemia observed in 20-30% of people with
      this syndrome. These disorders, what was shown also in our own studies, are
      existing in different intensity in patients treated with maintenance
      haemodialysis [3], peritoneal dialysis [4] and after renal transplantation as
      well [5]. Mechanism of hypertriglyceridemia, despite over thirty years of
      studies, is still not finally elucidated. The opinion that it is a result of
      impaired triglyceride removal (due to decreased activities of both lipoprotein
      and hepatic lipases) is well documented, however the role of lipogenesis in its
      development is obscure [6, 7]. The reports concerning this problem contain
      contradictory data. In our studies performed several years ago we have shown that
      lipogenesis rate in white adipose tissue of uremic rats is significantly
      augmented [8, 9, 10] due to activation of free fatty acid synthase. Therefore,
      recently we paid once again our attention on the activity of this lipogenesis
      rate limiting enzyme responsible for the long term regulation. We measured its
      activity, protein abundance and mRNA level in liver and epididymal white adipose
      tissue of rats with surgically induced renal failure (two-stage subtotal
      nephrectomy). The results support the thesis that lipogenesis takes a part in a
      hypertriglyceridemia found in renal failure. There have been observed a
      significant increase in plasma triglyceride and VLDL concentrations in uremic
      animals and it was associated with the increase of FAS activity, FAS protein
      abundance and FAS mRNA. The results were similar in both studied tissues.
      Moreover, there have been also observed the increased activities of malic enzyme,
      glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. All these
      enzymes participate in NADPH production, which is a necessary substrate for fatty
      acid biosynthesis [11, 12, 13]. Concluding, it appears that the rise in plasma
      triglyceride and VLDL concentrations observed in CRF rats is not only the result
      of increased liver and white adipose tissue lipogenesis rate. One has to
      remember, that these date are strictly original and enabling to elucidation
      further pathogenesis of hyperlipidemia in CRF. In the second set of experiments
      performed also in rats with experimentally induced CRF we have found that
      hypercholesterolemia observed in those animals is dependent on the significant
      activation of cholesterol synthase, induced by increased production of this
      enzyme (increment of protein abundance and synthase mRNA [14, 15].
      Simultaneously, we have performed original studies on the diurnal rhythm of
      cholesterologenesis, showing that activity of this process is significantly
      augmented during whole twenty four hours [15]. Summarizing, one have to underline
      that our observations have important impact to the elucidation of lipid
      disturbances pathomechanism. Nevertheless further studies are necessary to
      establish how experimental data are corresponding with human pathology.

PMID- 14974359
TI  - [Influence of erythropoietin on immunological system of patients with chronic
      renal failure].
AB  - Recombinant human erythropoietin (epoetin) administration is a well established
      therapy of anaemia in maintenance hemodialysis (HD) patients. During the
      treatment, along with an increase in haemoglobin (Hb) level also an improvement
      of physical and sexual activity and cognitive functions was observed. Moreover,
      recent studies have shown an impact of epoetin on lipid-carbohydrate and protein
      metabolism, endocrinological functions and immune system [1-7]. It is still
      unclear whether all these changes are caused by direct epoetin activity or they
      are associated with the correction of anaemia and better oxygen supply and
      therefore an improvement of the conditions required for many metabolic function.
      The goal of the first study performed in our centre was to estimate the influence
      of epoetin alpha (Eprex) administered in the doses not affecting erythropoiesis
      (7-10 IU/kg/three times a week for 12 weeks) on serum levels of interleukin (IL)
      2, 6 and tumor necrosis factor TNF-alpha [8, 9]. 10 HD patients (3 F, 7 M) aged
      from 33 to 62 years participated in that study. The level of IL-2, IL-6 and TNF
      alpha was measured by means of bioassay using a highly sensitive cell line
      respectively CTLL, B9 and fibrosarcoma--WEHI 164 (clone 13). Cells viability was
      tested by colorimetric MTT assay. During the first period of observation stable
      Hb concentration and unchanged although significantly higher than in healthy
      people levels of TNF-alpha and IL-6 were noticed. Serum level of IL-2 increased
      significantly and in the 10 week it reached the values observed in healthy humans
      although after that period of time it dropped to the initial values. The aim of
      the following study was to estimate the influence of epoetin on IL-2, IL-10 and
      TNF-alpha production by whole blood cell culture [1, 2]. 10 HD patients (2 F, 8
      M) aged from 35 to 53 years receiving standard doses of epoetin alpha (Eprex) for
      six months (in vivo experiments) and another 10 HD patients (3 F, 7 M) aged from
      40 to 60 years not receiving epoetin participated in the study (in vitro
      experiments--cell culture were stimulated with different doses of (epoetin alpha-
      Eprex and epoetin beta--Recormon): 0.05; 0.1; 0.5; 1.0 IU/ml). IL 2 and TNF-alpha
      were measured using the bioassay mentioned above, IL 10 by ELISA immunoassay. The
      levels of IL10 increased in all epoetin treated patients and it was accompanied
      by transitory decrease of TNF-alpha. The levels of IL-2 increased in 7/10
      patients under the study. Addition of epoetin in vitro to the whole blood culture
      of HD patients before implementation of epoetin confirmed that it is able to
      directly stimulate IL-2 production. The highest levels of stimulation of IL-2
      secretion were observed for the physiological doses of epoetin (0.05 IU/ml). The
      aim of the more recent study was to examine changes in CD4+ and CD8+ T-cell
      subpopulations, the expression of the inhibitory molecule, CD152+ on T
      lymphocytes and the levels of IL-2, IL-6, IL-10, IL-12 and TNF-alpha in HD
      patients [10]. Additionally serum levels of C reactive protein (CRP), C3, C4
      components of complement and immunoglobulin IgG, IgM and IgA were measured. 14
      patients (8 F, 6 M) aged from 31 to 64 years receiving standard doses of epoetin
      alpha (Eprex) for twelve months (in vivo experiments) and another 4 HD patients
      (2 F, 2 M) aged from 43 to 57 years not receiving epoetin participated in the
      study (in vitro experiments--cell culture were stimulated with epoetin as in
      previous study). METHODS: IL-2, IL-6, and TNF-alpha were measured using bioassays
      described above, IL-12 and IL-10 by ELISA immunoassay. Expression of T-cell
      surface molecules was measured both in vivo by flow cytometry of lymphocytes
      sampled from peripheral blood and in vitro using whole blood cell culture
      stimulated with physiological as well as non-physiological doses of epoetin. The
      levels of C3, C4, IgG, IgM and IgA were estimated using nephelometric method.
      Compared with the findings before the start of epoetin therapy the CD4+/CD8+
      ratio increased after 1 year of follow-up, whereas the percentage of CD152+
      peripheral blood lymphocytes decreased. The increase of the CD4+/CD8+ ratio was
      dependent on a decrease of the percentage of CD8+ cells. The decrease of CD152+
      population affected mainly CD8+152+ T cells. All these effects became apparent
      after 6 months of epoetin treatment. In vitro stimulation of whole blood cultures
      revealed that the addition of physiological concentration of epoetin decreased
      the percentage of CD8+152+ T cells. The pattern of the cytokines shifted towards
      Th1 phenotype (increase of IL-2 and IL-12) with a decreased level of
      proinflammatory cytokines (decrease of IL-6 and TNF-alpha). Treatment with
      epoetin did not alter plasma CRP, C3, C4 components of complement,
      immunoglobulin, as well as total count of lymphocytes. Summing up, administration
      of epoetin to maintenance HD patients not only treats the anaemia but also
      results in favourable changes in immune system. Epoetin is probably not only
      hemopoietic factor but also an immunomodulatory cytokine.

PMID- 14974360
TI  - [Quality of life and therapy in the elderly patients on chronic peritoneal
      dialysis].
AB  - In this study quality of life adequacy of treatment was assessed in 32 PD
      patients over 65 years of age and compared with younger patients on PD (age 40 on
      average). Quality of life was examined with help of QLQ-C30 questionnaire,
      negative emotions with use of HADS and own Aggression Scale, life satisfaction on
      the Cantril's Ladder. Total weekly clearances were used for adequacy assessment
      as well as nutrition parameters and rate of anaemia and EPO use. Frequency of
      complications was also compared. Elderly patients were starting dialysis with
      lower GFR, but in the course of observation neither total clearances nor
      nutrition parameters and degree of anaemia did not differ between the groups.
      Elderly used EPO significantly less frequently in comparison to the younger
      patients. Peritonitis rate was similar and exit site infections were less
      frequent in elderly population. There was no difference between quality of life
      and level of negative emotions between the groups. IN CONCLUSION: PD appears to
      be effective and acceptable method of dialysis for the elderly.

PMID- 14974361
TI  - [Malnutrition -- inflammation -- atherosclerosis (MIA syndrome) in patients with
      renal failure].
AB  - Cardiovascular disease (CVD) is the major cause of death in end-stage renal
      disease (ESRD). Malnutrition may worsen patient outcome by aggravating existing
      inflammation and heart failure, accelerating atherosclerosis and increasing
      susceptibility to infection. Available data demonstrate that chronic
      inflammation, a non-traditional risk factor which is observed commonly in uremic
      patients, play a key role in the genesis of both malnutrition and CVD in ESRD.
      Moreover, inflammation is associated with congestive heart failure. Pro
      inflammatory cytokines are pivotal to the inflammation. There is evidence that a
      chronic inflammation with activation of C-reactive protein, interleukin-6, tumour
      necrosis factor alpha and other cytokines is associated with increased oxidative
      stress and endothelial dysfunction in ESRD patients. Strong relations between
      malnutrition, inflammation and atherosclerosis in ESRD patients suggest the
      presence of a MIA (malnutrition, inflammation, and atherosclerosis) syndrome,
      which is associated with high mortality rate. Thus, it could be speculated that
      suppression of the vicious cycle of malnutrition, inflammation and
      atherosclerosis (MIA) would improve survival in ESRD patients. Therefore, the
      early stage of chronic renal failure is the ideal time to start therapeutic
      interventions.

PMID- 14974362
TI  - [Arterial hypertension in glomerulonephritis].
AB  - Numerous factors causing the disturbances of pressure natriuresis mechanism may
      be involved in the development of arterial hypertension in kidney diseases. In
      particular patients with parenchymatous kidney disease, the relative effect of
      the impaired renal sodium excretion causing extracellular fluid volume expansion
      and the disequilibrium of vasoconstricting and vasorelaxating factors may differ,
      and in addition, these effects are influenced by the type of kidney disease, the
      degree of the kidney function impairment and sodium intake. In our studies on the
      hypertension in kidney disease we have choosen the evaluation of incidence of
      hypertension in the early stage of primary glomerulonephritis (GN) and the
      comparison of distribution of genotypes and alleles depending on
      insertion/deletion polymorphism of angiotensin converting enzyme (ACE) gene in
      patients with early stage of GN and healthy subjects. Arterial hypertension was
      diagnosed according to actual criteria in 46% out of 74 patients with early stage
      of GN. It was also found that hypertension was more common in patients with
      nephrotic syndrome (63%) than in patients with lower proteinuria (36% of
      patients). Among 50 patients with early stage of GN the distribution of genotypes
      and alleles depending on the polymorphism ACE gene was significantly different
      from 100 healthy controls. These results indicate that hypertension is often
      present in early stage of GN, particularly in patients with nephrotic syndrome
      and depends on the morphological type of glomerular disease. Further studies are
      needed for verification of the role of ACE gene polymorphism in the
      predisposition to development of GN and associated arterial hypertension.

PMID- 14974363
TI  - [Evaluation of selected interleukins, tumor necrosis factor, insulin and leptin
      in obese patients with hypertension].
AB  - Both hypertension and obesity are speculated to stimulate inflammation process.
      THE AIM OF THE STUDY: Evaluation of selected inflammatory markers in obese
      hypertensives and estimation of their relationship to selected anthropometric and
      biochemical parameters. 32 patients with hypertension (group I), 34 patients with
      obesity and hypertension (group II) and 16 healthy volunteers (control) were
      studied. Percentage of fat content (%FAT) was estimated. Serum concentration of
      tumor necrosis factor (TNF-alpha), interleukins (IL-4, IL-6, IL-10), leptin,
      insulin were measured. Insulin resistance ratio (IRI/G) was calculated as an
      insulin: glucose ratio. Higher concentrations of TNF-alpha, IL-4, IL-6, IL-10,
      leptin, insulin, IRI/G ratio as compared to a control were found in both
      investigated groups. In group II higher TNF-alpha, IL-10, leptin, insulin and
      IRI/G as compared to group I were observed. In group II correlations between in
      (TNF-alpha) and BMI, %FAT, insulin, IRI/G ratio and SBP (systolic blood pressure)
      were found. BMI and TNF-alpha emerged as independent predictors of SBP.
      CONCLUSIONS: 1. Hypertension is associated with increased level of inflammatory
      markers. 2. Obesity can aggravate inflammation in patients with hypertension. 3.
      TNF-alpha should be considered as a potential player in the state of insulin
      resistance in obese hypertensives. 4. Both BMI and TNF-alpha emerged as
      independent predictors of SBP.

PMID- 14974364
TI  - [Evaluation of acute phase proteins in hypertensive and obese patients].
AB  - The inflammatory process contributes to the development of atherosclerotic
      changes. The aim of this study was to evaluate concentrations of selected acute
      phase proteins (APP) and their glycosylation profile in hypertensive subjects. 92
      hypertensive patients (53 men and 39 women, average age 45.1 yrs) were recruited
      to the study. Hypertension was proved to be essential, mild to moderate (mean
      blood pressure values were 141/87 mmHg). The control group comprised 75 healthy
      persons in comparable age. In all subjects assessment of C-reactive protein
      (CRP), alpha 1-acid glycoprotein (AGP), alpha 1-antichimotripsin (ACT),
      transferrin, alpha 1-antitripsin (rocket immunoelectrophoresis method) and C3c
      and C4c complement fractions (radial immunoelectrophoresis according to Mancini)
      were performed. Evaluation of glycosylation profile and reactivity coefficient
      (RC) for AGP were done by means of affinity immunoelectrophoresis with
      concanavalin A as a ligand (according to Bog-Hansen). When compared to the
      control group hypertensive subjects had significantly higher C-reactive protein
      and interleukin 6 concentrations. Level of transferrin (negative APP--decreasing
      in the course of the inflammatory process) was statistically lower in the studied
      group. Hypertensive patients were also found to have elevated AGP-AC values
      proving acute character of the inflammatory reaction. The intensification of the
      inflammatory reaction was greater in the subgroup of hypertensive patients with
      unsatisfactory control of blood pressure. CONCLUSIONS: 1. Hypertension may evoke
      the acute phase reaction. 2. Quantitative and qualitative changes in acute phase
      proteins observed in hypertension prove that hypertension itself is an acute
      inflammatory condition. 3. Markers of acute phase response are particularly
      strongly expressed in smokers and subjects with insufficient control of blood
      pressure. The most probable factor leading to the enhanced acute phase response
      in hypertension is interleukin 6.

PMID- 14974365
TI  - [Cytokines and growth factors serum level and renal allograft function
      (preliminary report)].
AB  - Long-term cyclosporine nephrotoxicity, subclinical rejections are risk factors of
      chronic allograft nephropathy. In a prospective, randomized study 44 pts. were
      randomized either to a reduced dose of CyA and daclizumab (group A, n = 22) or to
      a normal dose of CyA without daclizumab (group B, n = 22). Both groups were
      treated with MMF and prednisone. Number of rejection episodes was the primary
      endpoint. The secondary endpoints were renal function; histological parameters
      related to CyA; serum level of TGF-beta, PDGF-BB, blockade of CD25 molecule and
      surface expression of CD3, CD4, CD8, CD69, CD11a, CD49d, CD28, CD152 molecules in
      the subpopulations of T cells in the peripheral blood. A low incidence of
      clinically suspected rejection episodes were observed (19% in group A and 12.4%
      in group B; NS). The protocol biopsies at 3 month emerged 7 subclinical rejection
      episodes (4 in group A and 3 in group B). Serum creatinine level did not differ
      between examined groups. Chronic histopathologic changes related to CyA
      progressed significantly at the 3 month biopsies in both groups (with no
      differences between groups). Serum TGF-beta, PDGF did not differ between groups.
      Expression of CD25, CD152 molecule was significantly lower in group A than in
      group B. Immunosuppression regiment with low CyA dose with daclizumab, MMF,
      prednisone seems to be efficient and safe in low-risk rejection kidney allograft
      recipients.

PMID- 14974366
TI  - [The usefulness of tubular and glomerular proteinuria measurement in non-invasive
      diagnosis of vascular changes accompanying chronic allograft nephropathy].
AB  - Chronic allograft nephropathy (CAN) is the most important cause of late renal
      allograft loss. The standard diagnosis of CAN is based on pathological
      examinations according to Banff'97 scheme. The aim of the study was to evaluate
      the usefulness of tubular and glomerular proteinuria in non-invasive recognition
      of vascular changes accompanying CAN (AH--arteriolar hyaline thickening, CV-
      vascular fibrous intimal thickening). beta 2- and alpha 2-microglobulin (beta 2-m
      and alpha 2-m), albumin (alb), immunoglobulin G (IgG), total protein (tp) and
      creatinine (cr) concentration were measured in the second time urine specimen in
      66 renal allograft recipients. Then the subsequent renal biopsies were done. The
      aim of statistical analysis (MANOVA, Stepwise Discriminant Analysis, SDA) was to
      diagnose CV and AH changes based on results of urine analysis listed above and
      the patient's age, time after transplantation and serum creatinine level (scr).
      Results obtained with statistical analysis were in 90.91% and 87.69% identical
      with CV and AH pathological diagnoses, respectively.

PMID- 14974367
TI  - [Complement split product C4 as the indicator of immunological activity in
      chronic allograft rejection].
AB  - The patients after renal transplantation with deteriorating graft function were
      included to the study. The aim of the study was to establish the usefulness of
      stabile complement split product C4d expression as the independent indicator of
      immunological activity in chronic rejection. The C4d expression was studied on
      fresh frozen tissue with immunofluorescence method. The intensification of
      immunosuppression regimen was also introduced and azathioprine was exchanged with
      mycofenolate mofetil. The protocol biopsies a year after inclusion are planned to
      be done. In our study there was positive correlation between C4d expression and
      previous acute rejection episodes, morphological changes specific for chronic
      rejection and clinical improvement after immunosuppression enhancement.

PMID- 14974368
TI  - [The influence of lamivudine therapy on the course of chronic hepatitis B in
      renal allograft recipients].
AB  - The aim of this study was to evaluate efficacy and safety of lamivudine therapy
      in renal allograft recipients with chronic hepatitis B infection. Twenty-four
      patients with chronic hepatitis B after renal transplantation were observed. We
      obtained HBV replication blockage in 95% of patients, in half of them also ALT
      normalisation was observed. Delayed HBV replication blockage was observed in
      patients with prolonged duration of haemodialysotherapy or HBV infection and HCV
      coinfection, although listed parameters did not influence overall treatment
      efficacy. After lamivudine discontinuation HBV replication relapsed, in part of
      patients with ALT activity elevation. We did not observed any serious adverse
      reactions under lamivudine therapy.

PMID- 14974369
TI  - [Renovascular hypertension: is it only the top of the iceberg?].
AB  - Essential hypertension accounts for 95% of all cases of hypertension. A small
      number of patients (between 2% and 5%) have a reversible disease as the cause for
      raised blood pressure. Unilateral and bilateral renal artery stenosis may be
      responsible for secondary hypertension. Diagnosis and treatment of renal artery
      stenosis are of a great importance. Revascularization of ischemic kidney may
      correct blood pressure control and preserve renal function. Much data suggest
      close pathophysiological relation between renal artery stenosis, ischemic
      nephropathy and development of hypertension. However, it should be stressed that
      not every renal artery stenosis leads to hypertension and ischemic nephropathy.
      Therefore diagnosis of renal artery stenosis in hypertensive patient is not
      always equivalent with renovascular hypertension. The true prevalence of renal
      artery stenosis is unknown. In unselected population it accounts for less than 1%
      of hypertensive patients. Renovascular etiology of hypertension may be suggested
      by abrupt onset of hypertension, resistant and malignant hypertension or
      recurrent pulmonary edema of unknown etiology. Physical examination may reveal
      bruits over major vessels, including the abdominal aorta and renal arteries. The
      principle aim of the renal artery stenosis investigation is to confirm presence
      and size of vessel obstruction and its association with hypertension. Typical
      evaluation is based on imaging techniques and physiological studies. Former
      include: doppler duplex ultrasonography, conventional angiography, intraarterial
      and intravenous digital subtraction angiography, computed axial tomography,
      magnetic resonance angiography and intravascular ultrasonography. Functional
      studies are occasionally used. These are renal scintigraphy, evaluation of plasma
      renin activity in renal veins and evaluation of plasma rennin activity after ACE
      inhibition. Treatment of patients with renal artery stenosis and hypertension
      should restore vessel patency and inhibit its occlusion. Revascularization should
      elicit an improvement in or normalization of blood pressure control and renal
      function. Therapeutic approach include percutaneous renal artery angioplasty
      (PTRA), with or without stenting, revascularization by surgery and
      pharmacotherapy. PTRA is currently the first choice option. In general, it is
      simpler and similarly effective as surgical reconstruction. In some cases PTRA is
      completed with stent placement. It prevents immediate recoil but does not
      completely eliminate restenosis of revascularized artery. Surgical bypass is
      currently reserved for patients in whom PTRA and stenting fail and in patients
      with extensive atherosclerotic lesions. Patients with renal artery stenosis and
      hypertension should be provided with pharmacological treatment according to
      current recommendations. Specific procedures to limit associated risk factors of
      atherosclerosis should also be introduced.

PMID- 14974370
TI  - [The role of magnetic resonance angiography in the diagnosis of renovascular
      hypertension].
AB  - This review presents the techniques of magnetic resonance imaging used in the
      evaluation of renal arteries and renal function. The advantages and disadvantages
      of magnetic resonance angiography were described and compared with another
      imaging modalities including standard angiography, doppler ultrasound and CT
      angiography. The MR techniques used for the assessment of renal function, such as
      MR renography, PC flow measurements and diffusion-weighted imaging, were
      presented.

PMID- 14974371
TI  - [Non-traditional atherosclerosis risk factors in patients with renal artery
      stenosis and hypertension].
AB  - The most investigated novel risk factors of atherosclerosis are: fibrinogen (Fb),
      homocysteine (Hcy), lipoprotein (a) (Lp(a)), plasminogen activator inhibitor (PAI
      1), markers of inflammation and infectious factors. Atherosclerotic renal artery
      stenosis (RAS) is a manifestation of generalized atherosclerosis and often
      coexist with hypertension and renal failure. The aim of the study was to assess
      plasma concentration of Hcy, von Willebrand factor (VWF), (Lp(a), Fb, PAI-1, and
      assessment of ACE gene polymorphism in pts with RAS and hypertension. The study
      included 15 patients with RAS (mean age 51.4 +/- 16.5 yrs) and 27 healthy
      volunteers (C) (mean age 42.9 +/- 9.5 yrs). Plasma concentrations of Hcy were
      significantly higher in RAS (11.0 +/- 3.9 mumol/L) than in C (6.8 +/- 1.3
      mumol/L). Plasma concentration of VWF was also significantly higher in RAS than C
      (104.7 +/- 40 vs 73.6 +/- 20%) as was FB concentration (325.9 +/- 70.0 vs 256.2
      +/- 54.7 mg%). DD genotype was present in 45% of RAS pts and in 12% of controls.
      In patients with atherosclerotic RAS novel markers of atherosclerosis may be an
      additional risk factor in the development and progression of atherosclerotic
      lesions.

PMID- 14974372
TI  - [Serum concentration and urinary excretion of soluble receptors for tumor
      necrosis factor in patients with primary glomerulonephritis].
AB  - In sera and urine of healthy and diseased patients two soluble types of TNF
      receptors--p55--sTNF RI and p75--sTNF RII have been detected. They can protect
      cells against excessive cytotoxic activity of TNF-alpha in vitro and in vivo. The
      aim of the study was to investigate the prognostic significance and role of sTNF
      R in various types of glomerular diseases. We studied 49 patients with primary
      glomerular diseases (5 minimal change--MC; 4 focal glomerulosclerosis--FSGN; 4
      membranous nephropathy--MN; 12 mesangial proliferative GN--MSPGN; 18 IgA
      nephropathy--IgAN; and 6 membranoproliferative GN--MPGN) and 10 healthy persons.
      Renal biopsies were evaluated by light and immunofluorescence microscopy. STNF RI
      and sTNF RII concentrations were measured by ELISA (BIOSOURCE international
      kits). The treatment of patients consisted of 3 to 5 i.v. methylprednisolone
      pulses (1.0 g per single dose, average total 1.0 g/20 kg given alternate days)
      followed by oral prednisone 20 to 25 mg/day and six monthly i.v. cyclophosphamide
      0.6 g/1 m2/month. The studied groups showed a significantly higher concentration
      of sTNF RI and sTNF RII in their sera and urine when compared with the control.
      In patient groups serum Cr showed significant correlations with volume of
      interstitial tissue in renal biopsy, correlation of serum Cr with serum sTNF RI,
      serum sTNF RI with serum sTNF RII and with urinary sTNF RI, serum sTNF RII with
      urinary sTNF RI and with urinary sTNF RII. The ratio of serum sTNF RI to serum
      sTNF RII in patients was unchanged compared to the controls but ratio of urinary
      sTNF RI to sTNF RII was higher in all patient groups except patients with MC. In
      patients with renal sufficiency (Cr < 1.3 mg/dl) and reduction of proteinuria >
      50% after 1 year of therapy urinary secretion of sTNF RII was higher before
      treatment than in patients with protein reduction < 50%. In patients with renal
      insufficiency and reduction of proteinuria > 50% urinary excretion of sTNF RI was
      lower than in patients with lower reduction of proteinuria (< 50%) after 1 year
      of therapy. Our results suggest that serum sTNF R could be useful as indicator of
      clinical activity of the disease and urinary excretion of soluble receptors as a
      predictor of effectiveness of immunosuppressive therapy.

PMID- 14974373
TI  - [Multifocal fungal infections in patients after renal transplantation undergoing
      immunosuppression].
AB  - The aim of the study was to estimate the prevalence of fungi in monofocal and
      multifocal infections in renal transplant recipients and the characteristics of
      60 species and intraspecies features of fungal strains isolated from the organ
      ontocenoses: oral cavity, rectum and genital organs in 32 patients undergoing
      permanent immunosuppression after renal transplantation. Fungal strains were
      recovered in 66 out of 96 samples (68.2% off all renal transplant recipients).
      There were in ontocenoses: oral cavity (65.6%), rectum (37.5%) and genital organs
      (25.0%). Monofocals mycosis were found only in 21.9% of the patients. Multifocal
      infections occurred in 68.2% and contained ontocenoses of oral cavity and rectum
      (34.4%) the most frequently. Trifocal infection occurred in 12.5% of all examined
      renal transplant recipients. Fungal strains identified using API 20 C and API 20
      C AUX (bioMerieux). The activity of 19 hydrolases was investigated using API ZYM.
      From among 41 strains of fungi the following were found: Candida albicans (31
      strains), Candida glabrata (5), Candida guilliermondii (2), Candida krusei (2)
      and Saccharomyces cerevisiae (1). The enzymograms were described for all strains
      and the highest activity was noted in case of: leucine arylamidase, acid
      phosphatase, esterase, naphtol-AS-BI-phosphohydrolase. The presence high mean of
      activity of this enzymes means high pathogenicity of C. albicans strains.

PMID- 14974374
TI  - [Assessment of autonomic nervous system by spectral analysis of heart rate and
      blood pressure in hemodialysed patients].
AB  - The aim of the presented study was to assess autonomic nervous system (ANS) among
      hemodialysed patients. Twenty-seven pts. were included to the study (15 M, 12 F)
      and as a control group 22 (12 M, 10 F) healthy persons were taken. To asses
      cardiovascular part of ANS we used Ewing battery, time and spectral analysis of
      heart rate variability (HRV) and spectral analysis of blood pressure variability
      (BPV). QT interval was analyzed from standard 12-lead ECG. The hemodialysed
      patients showed certain signs of autonomic dysregulation. Forty two percent of
      pts had abnormalities in Ewing tests most prevalent in parasympathetic part of
      ANS. Spectral HRV parameters were pathological in 44.4% patients. The low
      frequency component of BPV was significantly lower in HD patients without changes
      in the high frequency component. QT interval dispersion and corrected by heart
      rate QT interval dispersion were significantly higher in hemodialysed patients
      than in the control group.

PMID- 14974375
TI  - [Using clinical epidemiology to improve the quality of clinical research
      articles].

PMID- 14974376
TI  - Cialis is here. The soft sell.

PMID- 14974377
TI  - Prevention. Activists protest as CDC shifts to HIV identification.

PMID- 14974378
TI  - Top HIV experts convene at national HIV prevention conference.

PMID- 14974380
TI  - Senate approves child testing bill.

PMID- 14974379
TI  - Testing. Pregnant women go untested despite CDC recommendations.

PMID- 14974381
TI  - Texas ADAP administrator loses whistleblower protection.

PMID- 14974382
TI  - Awareness. Black Americans unaware HIV treatment options available.

PMID- 14974383
TI  - Blood supply. 5 charged with knowingly selling own HIV-positive blood.

PMID- 14974385
TI  - Criminal transmission. HIV-infected man gets prison for unprotected sex.

PMID- 14974384
TI  - Discrimination. HIV-positive man drops suit after receiving home-care offer.

PMID- 14974386
TI  - Discrimination. San Francisco nondiscrimination ordinance upheld.

PMID- 14974387
TI  - Sentencing. Rehearing set to review sentence of HIV-positive man.

PMID- 14974388
TI  - Drug patent. Court rejects Glaxo's motion to dismiss AZT patent lawsuit.

PMID- 14974389
TI  - ADA. Disability discrimination claim fails for nondisabled worker.

PMID- 14974390
TI  - Guinean youth devise innovative prevention program.

PMID- 14974391
TI  - Tips for organizational effectiveness now online.

PMID- 14974392
TI  - Agency homes mother-to-child HIV prevention programs.

PMID- 14974393
TI  - Controversial measures, activities mark World AIDS Day.

PMID- 14974394
TI  - Clinton: AIDS threatens stability.

PMID- 14974395
TI  - Medical center cleared of faulty sterilization accusation.

PMID- 14974396
TI  - Disclosure. SSA worker cleared of violating HIV patient's privacy.

PMID- 14974397
TI  - Africa finds drug giants guilty of excessive pricing.

PMID- 14974398
TI  - Drug pricing. AHF to file suit against Glaxo for African AIDS-related deaths.

PMID- 14974399
TI  - Patent infringement. Court denies motion to alter patent claim decision.

PMID- 14974400
TI  - Denial of HIV-positive man's SSI benefits vacated on appeal.

PMID- 14974401
TI  - Discrimination. U.S. survey finds 'massive' HIV/AIDS civil rights violations.

PMID- 14974402
TI  - Discrimination. ACLU documents abuses against people with HIV.

PMID- 14974403
TI  - Transfusion. HIV-positive hemophiliac must reimburse Medicaid.

PMID- 14974404
TI  - Variance appropriate to accommodate AIDS housing.

PMID- 14974405
TI  - CalPERS to reopen drug giant's AIDS drug-pricing issue.

PMID- 14974406
TI  - What are HIV+ persons' HIV prevention needs?

PMID- 14974407
TI  - "HIV stops with me".

PMID- 14974408
TI  - Effective point-of-care rapid HIV testing at labor and delivery.

PMID- 14974409
TI  - Kiss and gel.

PMID- 14974410
TI  - Senators applauded for new legislation promoting HIV prevention technology for
      women.

PMID- 14974411
TI  - HIV/AIDS among US women: minority and young women at continuing risk.

PMID- 14974412
TI  - AIDS and the African-American community.

PMID- 14974413
TI  - Nutrition & pregnancy.

PMID- 14974415
TI  - Prayer in the lives of people with HIV.

PMID- 14974414
TI  - Healing HIV: mind, body, and spirit.

PMID- 14974416
TI  - Government prevention research 'hit list' draws protests from scientists. Recent
      NIH 'hit list' is unprecedented, they say.
AB  - Scientists, AIDS service organizations, and professional associations have
      denounced what they see as attacks on their work to stop the HIV/AIDS epidemic
      aimed at high-risk populations. In the past year, pressure has fallen on
      researchers mounted from Congress and the NIH, they say.

PMID- 14974417
TI  - Attacks on prevention work have increased. One researcher experienced in-depth
      federal audit.
AB  - Over the past three years, those who work in HIV prevention have come under
      increased political scrutiny. HIV-prevention programs first came under fire in
      the fall of 2001 from the Office of Inspector General and later the Department of
      Health and Human Services.

PMID- 14974418
TI  - Jails in unique position to ID high-risk population. Cook County in Illinois
      serves as model.
AB  - 10 million people pass through the United States correctional system each year,
      and 2 million of these people are incarcerated, while a large proportion of the
      remaining 8 million people spend at least a little time behind bars. In the midst
      of those unfortunate statistics, is an opportunity to identify and refer for
      treatment high-risk populations.

PMID- 14974419
TI  - Studies shed light on youth sex and drinking. Parents and teens don't see eye to
      eye.
AB  - Researchers looking into early sexual behavior and attitudes about sex among
      youths have found that alcohol use does play a role in sexual initiation, and
      that children have different attitudes about sexual behavior even as young as
      preteens.

PMID- 14974420
TI  - CDC emphasizing role of STDs in HIV care.
AB  - What do you do with a patient with stable HIV but presents with a new STD? The
      CDC is offering suggestions to providers fro handling this and other situations.

PMID- 14974421
TI  - FDA grants approval to fosamprenavir calcium.
AB  - The Food and Drug Administration has granted approval to fosamprenavir calcium
      (Lexiva), a protease inhibitor used to treat HIV infection.

PMID- 14974422
TI  - New horizons in the treatment of HIV.

PMID- 14974423
TI  - Antiretroviral news from the Chicago: the 43rd ICAAC.

PMID- 14974424
TI  - The HIV Research Network: a unique opportunity for real time clinical utilization
      analysis in HIV.

PMID- 14974425
TI  - Management of infants born to HIV infected mothers.

PMID- 14974426
TI  - Drug profile: fosamprenavir (Lexiva).

PMID- 14974427
TI  - The forgotten minority. Asians & Pacific-Islanders in New York battling HIV/AIDS.

PMID- 14974428
TI  - The United Nations report on HIV/AIDS in Asia.

PMID- 14974429
TI  - HIV prevention among NYC Asian immigrants.

PMID- 14974430
TI  - Choose HIV drugs that work for you.

PMID- 14974431
TI  - Sleepless in the city. What can I do to control my stressful thoughts and to get
      some sleep?

PMID- 14974432
TI  - Guidelines for food and water safety for persons with HIV.

PMID- 14974433
TI  - Leptomonas wallacei shows distinct morphology and surface carbohydrates
      composition along the intestinal tract of its host Oncopeltus fasciatus
      (Hemiptera: Lygaeidae) and in axenic culture.
AB  - Leptomonas wallacei is a monoxenic trypanosomatid that colonizes the digestive
      tract of the phytophagous hemipteran Oncopeltus fasciatus. This infection was
      specific and took place exclusively in midgut intestinal ventricles V3 and V4,
      and in the hindgut. Abundances of parasites in the hindgut were 54% less than
      those in the hindgut. Parasites in the hindgut were more slender and had a longer
      flagellum than those from the hindgut, which were rounded, with a shorter
      flagellum. Moreover, hindgut forms expressed sugar residues on the cell surface,
      recognized by the lectins from Griffonia simplicifolia-I (alpha-galactose, alpha
      N-acetyl-galactosamine) and Helix pomatia (N-acetyl-galactosamine); those sugar
      residues were not present in protozoa from the midgut. In culture, parasites were
      morphologically similar to midgut forms, but differed from them because they did
      not express sugar residues that bind to lectin (beta-galactose(1-3) N-acetyl
      galactosamine) from Arachis hypogaea.

PMID- 14974434
TI  - [Not Available].

PMID- 14974435
TI  - [Does maternal consumption of coffee during pregnancy increase the risk of
      stillbirth and infant death? A prospective follow-up study].

PMID- 14974436
TI  - The role of international medical graduates in America's small rural critical
      access hospitals.
AB  - CONTEXT: Critical access hospitals (CAHs) are a federal Medicare category for
      isolated rural facilities with 15 or fewer acute care beds that receive cost
      based reimbursement from Medicare. PURPOSE: This study examines the role of
      foreign-born international medical graduates (IMGs) in the staffing of CAHs.
      METHODS: Chief executive officers (CEOs) of CAH facilities answered a telephone
      survey on their use of IMGs and the characteristics of those IMGs in winter 2002
      (388 responded, for a 96% response rate). This descriptive report presents roles
      and characteristics of IMGs in CAH facilities and the opinions of the CEOs about
      these practitioners. FINDINGS: Overall, 1 (24%) in 4 admitting physicians in CAHs
      are graduates of non-US medical schools (compared with 23% of physicians
      nationally), although the rates are higher for CAHs in persistent poverty
      counties, CAHs that report recruitment problems, and CAHs with smaller medical
      staffs. Hospitals east of the Mississippi River are more heavily reliant on IMGs
      than hospitals in the west. Most IMGs are internists (59%) and most (61%) come
      from India, the Philippines, or Pakistan. Hospital administrators rate the
      clinical skills of their IMGs highly and their interpersonal skills only slightly
      lower. Almost half of CAH administrators said their communities recruited their
      first IMGs during or after 1994, the year of pro-IMG legislative changes.
      CONCLUSION: IMG physicians play a significant and possibly growing role in
      staffing CAHs.

PMID- 14974437
TI  - Transcanal labyrinthectomy in childhood: report of a case.
AB  - Vertigo in children is caused by several factors. One such factor is viruses
      (e.g., mumps, measles, and rubeola) afflicting the inner ear by various
      mechanisms. In the majority of cases, affected patients improve with clinical
      therapy and vestibular rehabilitation. We present the case of a child with
      vertigo as a sequela of mumps virus infection that did not improve with clinical
      treatment and vestibular rehabilitation. Consequently, the child was submitted to
      a transcanal labyrinthectomy followed by vestibular rehabilitation, with
      significant postprocedure improvement of symptoms. We discuss surgical
      indications, the technique used in this case, and the importance of vestibular
      rehabilitation in the postoperative period.

PMID- 14974438
TI  - Acute tinnitus and permanent audiovestibular damage after hepatitis B
      vaccination.
AB  - Yeast-derived recombinant DNA hepatitis B vaccine usage has been widely accepted
      since the early 1990s, especially for high-risk patients. Severe adverse effects
      have been reported infrequently. Certain neurological complications raise concern
      for hepatitis B vaccine: central nervous system demyelination, acute myelitis,
      acute cerebellar ataxia, and various peripheral mononeuropathies. Case reports on
      tinnitus, hearing loss, and vestibular damage are extremely scarce. The case
      presented here concerns a professionally active nurse, born in 1953, with a
      medical history of progressive renal failure and hemodialysis. Eleven hours after
      a second injection of the hepatitis B vaccine Engerix B, an acute left-sided
      tinnitus occurred and, a few hours later, severe left hearing loss and intense
      vertigo. Tinnitus and the sensation of vertigo regressed fairly quickly, but the
      hearing loss and the vestibular paresis were permanent. Increased interpeak
      intervals on auditory brain responses and lack of recruitment suggested that the
      lesion probably is located at the level of cranial nerve VIII. From a medicolegal
      point of view, this audiovestibular damage had to be considered an accident at
      work and not as an occupational disease.

PMID- 14974439
TI  - Finance issue brief: mandated benefits: breast cancer screening coverage
      requirements: year end report-2003.

PMID- 14974440
TI  - [Advances in the study on Hypericum japonicum Thunb. and its injections].

PMID- 14974441
TI  - Energy balance and body composition in sports and exercise.
AB  - Many athletes, especially female athletes and participants in endurance and
      aesthetic sports and sports with weight classes, are chronically energy
      deficient. This energy deficiency impairs performance, growth and health.
      Reproductive disorders in female athletes are caused by low energy availability
      (defined as dietary energy intake minus exercise energy expenditure), perhaps
      specifically by low carbohydrate availability, and not by the stress of exercise.
      These reproductive disorders can be prevented or reversed by dietary
      supplementation in compensation for exercise energy expenditure without any
      moderation of the exercise regimen. Energy balance is not the objective of
      athletic training. To maximize performance, athletes strive to achieve an optimum
      sport-specific body size, body composition and mix of energy stores. To pursue
      these objectives, athletes need to manage fat, protein and carbohydrate balances
      separately, but it is impractical for athletes to monitor these balances
      directly, and appetite is not a reliable indicator of their energy and
      macronutrient needs. To guide their progress, athletes need to eat by discipline
      and to monitor specific, reliable and practical biomarkers of their objectives.
      Skinfolds and urinary ketones may be the best biomarkers of fat stores and
      carbohydrate deficiency, respectively. Research is needed to identify and
      validate these and other markers.

PMID- 14974442
TI  - Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex
      agnus-castus L. (chaste-berry).
AB  - A methanol extract of chaste-tree berry (Vitex agnus-castus L.) was tested for
      its ability to displace radiolabeled estradiol from the binding site of estrogen
      receptors alpha (ERalpha) and beta (ERbeta). The extract at 46 +/- 3 microg/ml
      displaced 50% of estradiol from ERalpha and 64 +/- 4 microg/ml from ERbeta.
      Treatment of the ER+ hormone-dependent T47D:A18 breast cancer cell line with the
      extract induced up-regulation of ERbeta mRNA. Progesterone receptor (PR) mRNA was
      upregulated in the Ishikawa endometrial cancer cell line. However, chaste-tree
      berry extract did not induce estrogen-dependent alkaline phosphatase (AP)
      activity in Ishikawa cells. Bioassay-guided isolation, utilizing ER binding as a
      monitor, resulted in the isolation of linoleic acid as one possible estrogenic
      component of the extract. The use of pulsed ultrafiltration liquid chromatography
      mass spectrometry, which is an affinity-based screening technique, also
      identified linoleic acid as an ER ligand based on its selective affinity,
      molecular weight, and retention time. Linoleic acid also stimulated mRNA ERbeta
      expression in T47D:A18 cells, PR expression in Ishikawa cells, but not AP
      activity in Ishikawa cells. These data suggest that linoleic acid from the fruits
      of Vitex agnus-castus can bind to estrogen receptors and induce certain estrogen
      inducible genes.

PMID- 14974444
TI  - [A review on chronic uric-acid nephropathy treated with Chinese traditional
      medicine].

PMID- 14974443
TI  - New technologies: bioluminescence resonance energy transfer (BRET) for the
      detection of real time interactions involving G-protein coupled receptors.
AB  - The natural phenomenon of bioluminescence resonance energy transfer (BRET) has
      become an extremely useful tool for studying protein-protein interactions in the
      laboratory, including those involving G-protein coupled receptors (GPCRs). The
      technology involves fusion of donor and acceptor molecules to proteins of
      interest. Following assessment to ensure correct functionality, co-expression of
      fusion constructs in live cells enables their interaction to be studied in real
      time in a quantitative manner. Energy is transferred from the donor to the
      acceptor when in close proximity, resulting in fluorescence emission at a
      characteristic wavelength. The energy emitted by the acceptor relative to that
      emitted by the donor is termed the BRET signal. It is dependent upon the spectral
      properties, ratio, distance and relative orientation of the donor and acceptor
      molecules, as well as the strength and stability of the interaction between the
      proteins of interest. The ability to study interactions in live mammalian cells
      circumvents many of the problems associated with techniques such as co
      immunoprecipitation and yeast two-hybrid screening. Furthermore, the high
      sensitivity of BRET enables the study of proteins at physiological
      concentrations, a significant advantage over techniques that require high levels
      of protein expression. BRET technology has already made a substantial
      contribution to our understanding of GPCRs and protein-protein interactions, in
      particular by providing strong evidence that GPCRs homo- and hetero-oligomerize.
      New BRET detection systems and the potential for novel high throughput screening
      applications means that BRET promises to play an important role in future
      research and drug discovery.

PMID- 14974445
TI  - Primate cloning and stem cells--options and impacts.

PMID- 14974446
TI  - Embryonic-endometrial interactions at implantation in humans.

PMID- 14974447
TI  - Implantation in the baboon.

PMID- 14974448
TI  - Morphology, endocrinology and paracrinology of embryo growth and implantation in
      the rhesus monkey.

PMID- 14974449
TI  - The olive baboon (Papio anubis): a potential animal model to study the function
      of human leukocyte antigen-G (HLA-G).
AB  - The human class Ib major histocompatibility complex (MHC) molecule, HLA-G, is
      unique in its limited polymorphism, high expression in the placenta and
      generation of multiple transcripts by alternative splicing. The proteins encoded
      by these transcripts are believed to modulate maternal-fetal immunological
      relationships during pregnancy. The baboon placenta expresses Paan-AG, a novel
      MHC molecule that is evolutionarily related to the MHC-A locus but shares unique
      characteristics with HLA-G. In this brief review, we present evidence suggesting
      that Paan-AG may be the functional homologue of HLA-G, and propose that the
      baboon would compromise an excellent animal model for functional studies of HLA-G
      proteins in human pregnancy.

PMID- 14974450
TI  - The prevalence of anti-phospholipid antibodies in a selected population of Kenyan
      women and development of a non-human primate model.
AB  - The mechanisms by which anti-phospholipid antibodies (aPLs) may induce pregnancy
      losses, intrauterine growth retardation and pregnancy-induced hypertension are
      not clearly understood. Moreover, there is a controversy regarding the possible
      direct effects of these antibodies on the physiology of the placenta since the
      target antigens of these antibodies are intracellular antigens and are
      potentially inaccessible to the antibody. Also, controversy exists regarding the
      usefulness of the treatment regimens currently available. In this study, we
      present preliminary data on the prevalence of aPLs in a selected population (n =
      80) of Kenyan women visiting Kenyatta National Hospital, Nairobi, Kenya for
      obstetrical complications including recurrent pregnancy losses. Our results
      showed approximately 13.8% of the patients were positive for anti-cardiolipin
      antibodies whereas 33.8% were positive for aPS. Additionally, we screened 72 non
      human primates for presence of aPLs and our results showed that the olive baboon
      (Papio anubis) had the highest prevalence rate (52.2%, n = 23). Overall, our
      results suggest that the olive baboon may be a suitable animal model for studying
      the mechanism of action of the anti-phospholipid antibody and pregnancy
      complications associated with aPLs.

PMID- 14974451
TI  - Pre-eclampsia and vascular activation in women and non-human primates.

PMID- 14974452
TI  - The prevalence of endometriosis among African-American and African-indigenous
      women.
AB  - Endometriosis is gynaecological disorder, characterized by the growth of
      endometrial tissue outside the uterine cavity. It is the most common cause of
      pelvic pain and occurs in 20-25% of women with infertility. Although Sampson
      first described endometriosis in 1927, studies on the prevalence of endometriosis
      among African women are still lacking. The current thinking is that endometriosis
      rarely affects women from the African origin. However, in African-American women
      in the USA, endometriosis is one of the commonest indications for major
      gynaecological surgery and hysterectomy, and is associated with long hospital
      stay and high hospital charges. There is also some evidence that endometriosis is
      more commonly found in African-American patients from private practice than in
      African-American patients treated in public hospitals. The prevalence of
      endometriosis in African-indigenous women with infertility seems low, possibly
      due to a different life style (early pregnancy, increased risk for PID and
      blocked Fallopian tubes) and due to lack of laparascopic facilities and specific
      training of African gynecologists to diagnose ascites caused by endometriosis
      appear to be more frequently observed in African-indigenous of African-American
      women than in women with other ethnic backgrounds.

PMID- 14974453
TI  - Etiology of endometriosis: hypotheses and facts.

PMID- 14974454
TI  - Baboon model for fundamental and preclinical research in endometriosis.

PMID- 14974455
TI  - Endometriosis in the baboon.

PMID- 14974456
TI  - The future of endometriosis research: genomics and proteomics?

PMID- 14974457
TI  - Quantitative assessment of endometrial-peritoneal interaction in vitro: a non
      invasive diagnostic test for women with endometriosis?

PMID- 14974458
TI  - Medical treatment of endometriosis.

PMID- 14974459
TI  - Inhibition of endometrial peritoneal attachment in the prevention and treatment
      of endometriosis.

PMID- 14974460
TI  - Steroid and cytokine regulation of matrix metalloproteinases and the
      pathophysiology of endometriosis.

PMID- 14974461
TI  - Anti-angiogenic treatment of endometriosis: biochemical aspects.

PMID- 14974462
TI  - Infertility: addressing changes in its management in Africa.

PMID- 14974463
TI  - The need for infertility services in the developing world: the WHO point of view.

PMID- 14974464
TI  - Perception of infertility in two communities in Kenya.

PMID- 14974465
TI  - Defining mechanisms of interaction between enterohemorrhagic Escherichia coli
      O157:H7 and host epithelia.

PMID- 14974466
TI  - 6-Thioguanine can cause serious liver injury in inflammatory bowel disease
      patients.

PMID- 14974467
TI  - Clinical quiz. White sponge nevus.

PMID- 14974469
TI  - Gas chromatography problem solving and troubleshooting.

PMID- 14974470
TI  - The black death: A problem of population-wide infection.

PMID- 14974471
TI  - Birth spacing and infant mortality on the isle of Skye, Scotland, in the 1880s: A
      comparison with the town of Ipswich, England.

PMID- 14974472
TI  - Birth-baptism intervals in Whickham Parish, Co. Durham c. 1770-1820.

PMID- 14974473
TI  - Australian charities call for government reinvestment in screening.

PMID- 14974474
TI  - Panel eases US drug approval process.

PMID- 14974475
TI  - Urine test for renal-cell carcinoma.

PMID- 14974476
TI  - Hope fades for major public health projects.

PMID- 14974477
TI  - Tissue banks: who decides what is ethical?

PMID- 14974478
TI  - Mechanotransduction in root gravity sensing cells.
AB  - The analysis of the dose-response curve of the gravitropic reaction of lentil
      seedling roots has shown that these organs are more sensitive when they have been
      grown in microgravity than when they have been grown on a 1 g centrifuge in space
      before gravistimulation. This difference of gravisensitivity is not due to the
      volume or the density of starch grains of statoliths, which are about the same in
      both conditions (1 g or microgravity). However, the distribution of statoliths
      within the statocyte may be responsible for this differential sensitivity, since
      the dispersion of these organelles is greater in microgravity than in 1 g. When
      lentil roots grown in microgravity or in 1 g are stimulated at 0.93 g for 22 min,
      the amyloplasts sediment following two different trajectories. They move from the
      proximal half of the statocytes toward the lower longitudinal wall in the
      microgravity grown sample and from the distal half toward the longitudinal wall
      in the 1 g grown sample. At the end of the stimulation, they reach a similar
      position within the statocytes. If the roots of both samples are left in
      microgravity for 3 h, the amyloplasts move toward the cell centre in a direction
      that makes an average angle of 40 degrees with respect to the lower longitudinal
      wall. The actin filaments, which are responsible for this movement, may have an
      overall orientation of 40 degrees with respect to this wall. Thus, when roots
      grown in microgravity are stimulated on the minicentrifuge the amyloplasts slide
      on the actin filaments, whereas they move perpendicular to them in 1 g grown
      roots. Our results suggest that greater sensitivity of seedling roots grown in
      microgravity should be due to greater dispersion of statoliths, to better
      contacts between statoliths and the actin network and to greater number of
      activated mechanoreceptors. One can hypothesize that stretch activated ion
      channels (SACs) located in the plasma membrane are responsible for the
      transduction of gravistimulus. These SACs may be connected together by elements
      of the cytoskeleton lining the plasma membrane and to the actin filaments. They
      could be stimulated by the action of statoliths on the actin network and/or on
      these elements of the cytoskeleton which link the mechanoreceptors (SACs).

PMID- 14974479
TI  - William W. Montgomery, MD, 1923-2003.

PMID- 14974481
TI  - Fatal outcome of a hypersensitivity reaction to paclitaxel: a critical review of
      premedication regimens.
AB  - Hypersensitivity reactions (HSRs) to paclitaxel are frequently encountered in
      patients receiving this antitumour drug. Administration of histamine H1- and H2
      receptor antagonists and corticosteroids has been shown to reduce significantly
      the risk of developing an HSR in patients receiving taxanes. In this case report,
      we describe the fatal outcome of an HSR in a patient receiving paclitaxel despite
      short-course premedication. The level of evidence supporting the short-course
      i.v. premedication schedule is challenged, as it is not compatible with the
      pharmacokinetic properties of dexamethasone.

PMID- 14974482
TI  - State experiences with crowd-out under SCHIP.

PMID- 14974483
TI  - New approaches to non-emergency Medicaid transportation.

PMID- 14974484
TI  - Preventing cancer: using health dollars wisely.

PMID- 14974485
TI  - "Learning curves" of cardiac surgery in relation to risk stratification and
      hospital location.
AB  - AIM: The purpose of this study was to determine any significant differences in
      "learning curves" between private and public hospitals when the same senior
      surgeon was responsible during the initial phases of open-heart surgery programs
      development, in relation to risk stratification and hospital location. METHODS: A
      prospective review of 610 patients records was performed at a newly-opened
      cardiothoracic program in a public University Hospital (PUH) in the periphery of
      Greece, and a private institution (PI) with an experienced intensive care unit
      (ICU) in the capital city of Athens. Preoperative risk stratification, mortality
      and postoperative length of stay (LOS) were analysed between 1999 to 2001.
      RESULTS: At PUH 298 patients were operated and 312 patients at PI. There were 136
      low risk (EuroSCORE 0-2) and 474 medium and high-risk patients (EuroSCORE > or
      =3). There was no significantly elevated mortality or learning curve in low risk
      surgery either at PUH (57 patients with 1 death) or PI (79 patients and 1 death).
      In medium and high-risk surgery at PI there was no mortality in 68 patients
      operated by the senior surgeon and no learning curve in all 233 such patients. In
      240 medium and high-risk patients at PUH there was a learning curve despite the
      involvement of the same senior surgeon. In 1999 and 2000 the observed mortality
      (OM) in 150 patients was 15.33%, EuroSCORE 5.98, and in 2001 in 91 patients OM
      3.29%, EuroSCORE 5.95 with p=0.00.8 when "experienced" ICU staff was employed.
      LOS was significantly reduced in 97 patients in 2001 at PUH (8.7 d +/- 2.81 vs
      11.07 days +/- 7.9 in 1999 and 2000, p=0.046) confirming the existence of a
      learning curve at the PUH. No such change was observed at PI (8.2 days vs 7.8,
      p=0.45). CONCLUSION: No mortality differences or learning curve characteristics
      were detected for low risk operations either at PUH or PI. For medium and high
      risk surgery there appears to be a learning curve in PUH but not in PI despite
      senior surgeon involvement in both. The presence of an experienced ICU appears to
      play a critical role in the outcome of operations in newly opened cardiothoracic
      programs.

PMID- 14974486
TI  - The costs of depression in the workplace.

PMID- 14974487
TI  - The obesity epidemic.

PMID- 14974488
TI  - EAP follow-up in the workplace boosts alcohol treatment success.

PMID- 14974489
TI  - Triad's new market strategy: a threat to community hospitals.
AB  - Faced with unprecedented financial pressures, many nonprofit hospitals today
      contemplate hooking up with large corporations and converting to for-profit
      status. In the deals that result, the talk is largely about stock value and the
      interests of investors. The larger public-interest question of how the conversion
      will affect the health of community members often receives short shift. Most
      recently, Triad, an HCA spin-off, has emerged as a major player in the market for
      faltering nonprofits, zeroing in on institutions all the way from Alaska to North
      Carolina, and this has advocates worried, because the company can be singularly
      insensitive to community health care needs. But Triad is also remarkably adept at
      winning public favor. In this States of Health, we'll look at the broader public
      policy questions raised by such corporate health ventures, questions that point
      to the need for stronger oversight and regulatory mechanisms to assure that the
      public interest is protected in our increasingly market-driven health system.

PMID- 14974490
TI  - Sensory characterization of a ready-to-eat sweetpotato breakfast cereal by
      descriptive analysis.
AB  - The sweetpotato [Ipomoea batatas (L.) Lam], an important industry in the United
      States, has been selected as a candidate crop to be grown on future long-duration
      space missions by NASA. Raw sweetpotato roots were processed into flour, which
      was used to formulate ready-to-eat breakfast cereal (RTEBC). Twelve trained
      panelists evaluated the sensory attributes of the extruded RTEBC using
      descriptive analysis. The samples were significantly different (P<0.05) for all
      attributes. Twelve perceived sensory attributes, which could be used to
      differentiate the appearance, texture, and flavor of sweetpotato RTEBC, were
      described. The data could be used to optimize the RTEBC and for designing studies
      to test its consumer acceptance.

PMID- 14974491
TI  - Relapsing and painful horny excrescence of the sole: a case of ectopic plantar
      nail.

PMID- 14974492
TI  - Possible role of divalproex sodium in sedation induced by antipsychotic
      medications.

PMID- 14974493
TI  - Valproate for hostility in schizophrenia patients.

PMID- 14974494
TI  - Use of propofol for alcohol withdrawal delirium: a case report.

PMID- 14974495
TI  - Two cases of perospirone-induced mania in schizophrenia.

PMID- 14974497
TI  - Prescription drug access disparities among working-age Americans.
AB  - Working-age African Americans and Latinos are much more likely than white
      Americans to report they cannot afford all of their prescription drugs, according
      to a new study by the Center for Studying Health System Change (HSC). In 2001,
      nearly one in five blacks and one in six Latinos 18 to 64 years old did not
      purchase all of their prescriptions because of cost, compared with slightly more
      than one in 10 whites. Cost-related prescription drug access problems are
      considerably higher for people with chronic conditions, particularly African
      Americans. Regardless of race or ethnicity, uninsured working-age people with
      chronic conditions are at particular risk for not being able to afford all of
      their prescriptions, with about half reporting cost-related prescription access
      problems. Increased patient cost sharing for prescription drugs will likely
      increase prescription drug access disparities for insured African Americans and
      Latinos, especially those with chronic conditions.

PMID- 14974498
TI  - Getting along or going along? Health plan-provider contract showdowns subside.
AB  - Although contract negotiations between health plans and providers have remained
      tense during the past two years, overt impasses have declined, according to
      findings from the Center for Studying Health System Change's (HSC) 2002-03 site
      visits to 12 nationally representative communities. The balance of power
      stabilized during the period, with providers, particularly hospitals, solidifying
      their dominant negotiating positions and securing concessions from plans in the
      form of significant payment rate increases and more favorable contract terms.
      Many plans have recognized and accepted their weaker position relative to
      providers, suggesting the recent lull indicates plans have found it in their
      interests to accommodate provider demands for higher payments, rather than resist
      them and possibly trigger a contract showdown. Though no immediate change is
      likely in this environment, there are emerging forces that could swing the power
      pendulum back toward plans.

PMID- 14974499
TI  - [Pharmacological action of hesperidin].

PMID- 14974500
TI  - [A review of the study on anti-obesity therapies with traditional Chinese
      medicine].

PMID- 14974501
TI  - Postural control in order to prevent chronic locomotor injuries in top level
      athletes.
AB  - Chronic injuries of the locomotor apparatus represent the main cause of drop-out
      among top level gymnasts. The aim of the present paper was to verify whether the
      postural control, investigated by using an integrated approach and accordingly
      optimized, could be an effective tool for the secondary prevention of training
      related disorders of the locomotor apparatus, in a cohort of 20 young female
      athletes practicing rythmic gymnastic at top level. After a preliminary medical
      consultation all the subjects underwent a static and dynamic baropodometric test,
      an ophtalmological and a dental screening. Then athletes were given prescriptions
      based upon the results of the above named examination. After 6 months, symptoms
      were completely disappeared in 80% and remarkably improved in 20%, and at
      baropodometric test, the contact duration as well as the contact surface, the max
      and mean contact pressure were significantly increased in all the athletes. Our
      data show that the proposed integrated approach is actually an effective tool for
      the secondary prevention of training related disorders of the locomotor
      apparatus.

PMID- 14974502
TI  - Effect of Nd: YAG laser on titanium dental implants studied by AFM.
AB  - Bacterial contamination of dental implants is considered the main cause of
      implant failure. Recently, the laser treatment of the implant surface has been
      proposed as an useful method for decontamination. In such a view, the present
      study was conducted to investigate the effects of a Nd:YAG laser on the surface
      morphology of a titanium dental implant by means of an atomic force microscope.
      We demonstrated that, when the pulse energy of the laser was kept below 30 mJ,
      independently from the pulse rate, the laser-treated specimens exhibited a
      qualitatively similar surface morphology when compared to the untreated titanium
      implants, suggesting that the implant surface was unaffected by the treatment, in
      these particular conditions. We also found that, by cooling the implant surface
      with an air flow? during laser irradiation, the mean temperature of the implant
      was maintained under 37 degrees C. All these data taken together suggest the
      possibility to use Nd:YAG laser for the treatment of failing dental implants.

PMID- 14974503
TI  - Effects of physical activity on blood pressure monitoring and morphometric
      parameters of the left ventricle and of the abdominal aorta in healthy elderly
      subjects.
AB  - To investigate the effects of physical activity not only on morphometric left
      ventricular parameters, but also on the abdominal aorta diameter and on blood
      pressure, we enrolled 100 healthy subjects, 50 males and 50 females, aged between
      63 and 91 years (mean 73.3 +/- s.d. 7.7), each divided into two subgroups,
      sedentary and non sedentary, come to our observation for a diagnostic screening.
      For each subject an Echography was performed, by using an Acuson 128XP10
      apparatus, equipped with a 2 MHz phased array probe, both for the study of the
      heart and for the study of the abdominal aorta. Then, all the subjects underwent
      24 hours blood pressure monitoring by using a P6 Delmar apparatus in order to get
      mean systolic and diastolic blood pressure. Diastolic blood pressure was
      significantly related to physical activity (sedentary > non sedentary, P < 0.01),
      while systolic blood pressure was not; left ventricle and abdominal aorta
      diameters were both significantly related to sex (males > females, P < 0.001),
      but left ventricle diameter was significantly related to diastolic blood pressure
      (P < 0.01), while abdominal aorta diameter was significantly related to systolic
      blood pressure (P < 0.001). Our data suggest that physical activity might be
      strongly recommended to control blood pressure.

PMID- 14974504
TI  - Neuromuscular patterns of finger movements during piano playing. Definition of an
      experimental protocol.
AB  - Body movements require the activity of muscles fired by their motor neurons,
      controlled and coordinated according to central motor patterns modulated by the
      sensory feedback. The direct analysis of movements and forces produced by
      muscular activity can provide useful information into anatomical details of
      difficult observation. For instance, the analysis of movement trajectories can be
      used to obtain some insight into the underlying neuromuscular processes. Piano
      playing is a learned ability which links natural hand and finger movements in a
      complex and well-codified pattern. In the present study, the repeatability of
      finger movements was assessed in pianists of different experience. Five pianists
      (two females, 9, 23 years; three males, 24, 39, 70 years; all professionals)
      played nine two-octave C-major scales at 80, 112 and 160 bpm. The three
      dimensional coordinates of their right hand fingers were digitized by a motion
      analyzer. For each pianist, data from each of the three repetition performed at
      the same velocity were aligned on the time of onset of the first C keypress
      (thumb), and a coefficient of superimposition was computed. Significant (analysis
      of variance, p < 0.001) differences were found between pianists and velocities,
      with a significant pianist x velocity interaction. The oldest man (a well-known
      concert player) was the less repeatable (mean superimposition 65.8%, SD 17), the
      39-y-old man (a piano teacher) was the most repeatable (mean superimposition
      81.4%, SD 8.1). In both of them, the thumb was the most repeatable finger; in the
      girl, the fifth and fourth fingers scored the best repeatability. The fastest
      scales were the less repeatable in the 70 and 24-y-old men, and the most
      repeatable in the 39-y-old man and 23-y-old woman. Even a simple and basic piano
      exercise can be performed with different movement patterns, without a direct
      relationship to the pianist experience. Apparently, repeatability was lower in
      concert pianists than in teachers and learners.

PMID- 14974505
TI  - Three-dimensional geometrical models of the inguinal region. Towards a new
      stereology.
AB  - In this work we studied the inguinal-abdominal region and the inguinal canal
      using three-dimensional geometrical models. We built the models through computer
      aided geometric modeling techniques on the basis of observations during real
      dissections, operations and diagnostic medical imaging. The obtained models show
      in a complete modular synthesis and with a schematic iconology the structural
      organization of the anatomical districts in a logic sequence of layers and
      topographic and spatial relationships among its components. The models represent
      an amazing support to anatomy and clinical anatomy for teaching and research
      purposes on organogenesis, surgery and diagnosis.

PMID- 14974506
TI  - In vitro study of Human Dermal Fibroblasts seeded on two kinds of surgical
      meshes: monofilamented Polypropylene and multifilamented Polyestere.
AB  - Many different synthetic biomaterials have been recently proposed in the majority
      of the techniques for hernioplasty and pelvic floor surgery. Required qualities
      of an implantable prosthetic material have been well established in the past and
      today the biomaterials better performing to this purpose are the monofilamented
      Polypropylene (Marlex) and the multifilamented Polyestere (Mersilene). But, in
      spite of a wide surgical use of these two kinds of meshes, many failures of these
      implantations are reported leading to removal of the prosthetic implanted
      material. If some of these failures are due to errors in surgical technique,
      others seem to be due to inadequacy of the selected material, too much soft or
      too much stiff, or too much or too little incorporated into the host tissue. This
      experiment investigated the different behaviour of in vitro cultured Human Dermal
      Fibroblasts, seeded on specimens of both meshes and then observed by Light (LM)
      and Scanning Electron Microscopy (SEM). Around the multifilamented threads of
      Polyestere mesh, fibroblasts could grow very well, filling the holes and making a
      continous cell layer completely envelopping the mesh. At the same culture time,
      around the Polypropylene mesh only big groups of fibroblasts were evident at the
      thread interlacing points. Therefore, it could be concluded that both meshes
      stimulate good fibroblast attachment and proliferation but in a very different
      way and amount; it will be up to the surgeon to select the appropriate mesh
      according to the specific surgical purpose.

PMID- 14974507
TI  - Further observations on the sensitive innervation of some bird's proctodeum.
AB  - The AA. studied the autonomic and sensitive somatic innervation of some female
      bird's proctodeum, through the properly modified Ruffini's gold chloride method.
      The vegetative component was constituted by ganglion cells of different size,
      isolated or grouped to form ganglia, found along the course of nerve trunks or in
      the concurrent point of different nerve bundles. The sensitive somatic
      innervation was represented by free and encapsulated endings differently
      distributed in the thickness of the wall. The former were composed of thin
      networks, while the latter, located more frequently in the muscular tunica and in
      the subadventitial connective, were composed of encapsulated receptors classified
      as Pacini, Pacini-like and Herbst corpuscles. The morphology of these receptors
      was described and hypotheses were brought up about their probable functional
      role. The AA, also found, even if very rarely, helicoidal collagen fibres around
      nerve fascicles.

PMID- 14974509
TI  - Nurse-managed centers: increasing access to health care.

PMID- 14974510
TI  - Developing the academic nursing practice in the midst of new realities in higher
      education.
AB  - The academic nursing practice has a role in replenishing the diminished resources
      that confront higher education and, if well conceived and managed, is a viable
      option to support existing academic program stability and growth. An alternative
      model for defining the academic practice--beyond traditional nurse-managed
      centers--is presented in this article. The cohesive interconnection of the
      education, research, and practice missions is addressed with examples of how each
      contributes to a variety of communities of interest and expands professional
      nursing roles through innovative care model testing and development. With
      effective business planning and infrastructure support, faculty practice plans
      can evolve to a second generation, with heightened societal accountability for
      service, academic, and collaborative research outcomes.

PMID- 14974511
TI  - Academic nursing centers: the road from the past, the bridge to the future.
AB  - This article explores the development of academic nursing centers within an
      environment of evolving health policy and changing priorities and resources
      within nursing education during the past 3 decades. Etheredge's framework for
      this discussion identifies three health policy eras: the Age of Traditional
      Health Insurance (1965-1982); the Age of Regulated Prices for Government Programs
      (1983-1992); and the Age of Markets, Purchasing, and Managed Care (1993-2000). In
      this article, I suggest the current era is the Age of Uncertainty and
      Opportunity. Within each era, health policy changes are summarized, and changes
      in nursing education that influenced the evolution of academic nursing centers
      are identified. The uncertainty and opportunity of the current era is explored
      within the context of the Institute of Medicine (IOM) reports issued in 2000 and
      2001. The new vision for clinical education in the health professions described
      in the 2001 report provides new opportunities for academic nursing centers. To
      take advantage of these opportunities, these centers must focus on quality issues
      as they continue to maintain a precarious balance between meeting the service
      needs of their clients and the academic needs of the nursing programs that own
      them. Centers that maintain this balance will be a bridge to the future for
      quality health professions education.

PMID- 14974512
TI  - The academic nursing practice dean: an emerging role.
AB  - This article describes the contributions of academic nursing practice to nursing
      education; delineates the role characteristics and competencies needed by
      academic practice deans; and provides examples of the challenges and issues
      academic practice deans face related to nursing education, research, and
      practice. While schools' missions vary from a strong focus on education to
      multiple emphases on education, research, and practice, academic nursing practice
      has the potential to facilitate achievement in each of these areas. Academic
      nursing practice deans play important roles in advancing the missions of their
      schools through the clinical practice activities within the schools. Strong
      academic nursing practice programs can serve as catalysts for the development and
      refinement of new models of care delivery and for the development of future
      nursing leaders who are comfortable with innovation.

PMID- 14974513
TI  - Center for Integrated Health Care: primary and mental health care for people with
      severe and persistent mental illnesses.
AB  - The Center for Integrated Health Care capitalizes on the abilities, drive, and
      autonomy of advanced practice nurses, resulting in an exciting, timely academic
      nursing center exemplar. People with severe and persistent mental illnesses
      receive care that is targeted specifically to a population with chronic mental
      illnesses and tailored to the unique individual by integrating primary and mental
      health care. This Center is a partnership between Thresholds, a psychosocial
      rehabilitation center, staff and University of Illinois at Chicago, College of
      Nursing faculty. The Center's goals are to provide quality care, support teaching
      and learning for nursing and other health professional learners, and generate new
      knowledge related to the integration of mental and physical health care. To
      achieve long-term sustainability, the Center must partner with a federally
      qualified health center.

PMID- 14974514
TI  - Academic nursing practice in rural West Virginia.
AB  - This exemplar highlights how a rural academic nursing practice has been effective
      in facilitating the integration of the tripartite academic role of education,
      research, and service for one university faculty member. The integration of
      students into the practice is described. The experience provided them with
      critical insights into rural academic practice during their delivery of prenatal
      care services to a vulnerable population of women in rural Appalachia. This
      exemplar also describes the use of the academic nursing practice as a laboratory
      both for studying the specific problems of this vulnerable population of women
      and their families, and testing interventions tailored to the needs of the
      community. Finally, the other ways the academic nursing practice benefits faculty
      and students, including integration of educational technology into the practice
      setting and opportunities for faculty leadership in rural community development,
      are discussed.

PMID- 14974515
TI  - Associate degree nursing in a community-based health center network: lessons in
      collaboration.
AB  - This exemplar highlights the ability of community experiences to enhance nursing
      students' understanding of the principles of community-based care: advocating
      self-care; focusing on prevention, family, culture, and community; providing
      continuity of care; and collaborating. An innovative teaching-practice model
      (i.e., a nurse-managed "network" of clinics), incorporating service-learning, was
      created. The Network's purposes are to provide practice sites in community-based
      primary care settings for student clinical rotations, increasing the awareness of
      the civic and social responsibility to provide quality health care for
      disadvantaged populations; and to reduce health disparities by increasing access
      to free primary health care, including health promotion and disease prevention,
      for disadvantaged individuals. Network clients receive free health care,
      referrals, and guidance to effectively obtain additional health care resources
      for themselves and their families. The Network is a national pioneer in modeling
      the delivery of primary care services through a faculty-student practice plan,
      with leadership emanating from a community college.

PMID- 14974516
TI  - Senior care: making a difference in long-term care of older adults.
AB  - This article describes the creation of Senior Care, a practice of the University
      of Missouri Sinclair School of Nursing (MUSSON). Senior Care is a home care
      agency that specializes in care of frail older adults. Grant funds assisted
      Senior Care in start up, and the program generated more than 1.25 million dollars
      in service revenue during the past fiscal year. More than 300 students, from
      nursing and other schools across the university, have used Senior Care as a
      clinical or service-learning site, and it is currently the site of several
      studies, totaling more than 3 million dollars in funding. Senior Care is the
      service component of the MUSSON Aging in Place initiative. The next phase is the
      completion of Tiger Place, a living community for older adults, built in
      affiliation with Americare Systems. Senior Care and the Aging in Place initiative
      provide an excellent example of how nurses can be leaders in health system
      change.

PMID- 14974517
TI  - Complexity theory: a long-term care specialty practice exemplar for the education
      of advanced practice nurses.
AB  - This clinical exemplar highlights how an academic clinical practice supported
      gerontological nursing students as they learned evidence-based approaches to
      managing complex geriatric syndromes in long-term care. Urinary incontinence
      (UI), which occurs in more than two thirds of nursing home residents, was the
      focus of the faculty practice. Advanced practice nursing skills developed by
      students included advanced physical assessment and diagnostic reasoning
      techniques, critical appraisal of the scientific evidence for UI management, and
      the ability to teach evidence-based approaches to UI care to bedside nursing
      staff. Outcomes of the practice for the facilities included improved detection of
      urinary retention, reduced wetness rates, and strengthened systems of care for
      UI. Student outcomes included an increased sense of self-efficacy in management
      of UI and other complex geriatric problems. Complexity theory guides a discussion
      of how curriculum design and research-based practices can be implemented to
      enhance both student and facility outcomes.

PMID- 14974518
TI  - Geospatial information technology: an adjunct to service-based outreach and
      education.
AB  - This exemplar highlights how geospatial information technology was effective in
      supporting academic practice, faculty outreach, and education initiatives at the
      University of Mississippi School of Nursing. Using this cutting-edge technology
      created a community-based prototype for fully integrating point-of-service
      research, practice, and academics into a cohesive strategy to influence change
      within the health care delivery system. This exemplar discusses ways this
      knowledge benefits practice and curriculum development; informs critical decision
      making affecting the people we serve; underscores the vital role nurses play in
      linking this technology to practice; and develops community residents as partners
      in their own health and that of the community.

PMID- 14974519
TI  - The Governor's Wellmobile: Maryland's mobile primary care clinic.
AB  - This article describes the development and implementation of the Governor's
      Wellmobile program. Designed to increase access to community-based health care
      for uninsured, underserved populations and to provide innovative clinical
      practice, research, and education opportunities for students and faculty, this
      fleet of four full-service, primary care clinics "on wheels" is managed and
      operated by the University of Maryland School of Nursing, demonstrating that
      nurse-managed practice models are valuable to the state's health care delivery
      system. Issues of long-term financial sustainability are presented, as well as
      lessons learned about the importance of public, private, and philanthropic
      partnerships and political support in ensuring the success of such programs.

PMID- 14974520
TI  - Immune system modulation in the highly sensitized transplant candidate.
AB  - Heart transplantation can be a lifesaving option for patients with end-stage
      heart failure. However, implanting recipients with an organ or tissue from a
      donor presents immunologic challenges. Sensitized recipients are at risk for
      hyperacute rejection because of the presence of preformed antibodies. Immune
      modulation with cyclophosphamide, plasmapheresis, and intravenous gamma globulin
      are methods used to desensitize transplant candidates with preformed anti-HLA
      antibodies to achieve successful transplantation.

PMID- 14974521
TI  - Cardiac allograft vasculopathy.
AB  - The purpose of this article is to discuss the pathogenesis, characteristics, and
      treatment modalities for heart transplant recipients with cardiac allograft
      vasculopathy (CAV). Cardiac transplantation has become an acceptable mainstream
      treatment for end-stage cardiac disease. Unfortunately, CAV is the leading cause
      of death after the first year of transplant. CAV is an accelerated form of
      obliterative coronary artery disease that occurs in the heart transplant
      recipient. Currently, retransplantation is the only definitive treatment. Ethical
      concerns and the shortage of donor organs present a huge obstacle to
      retransplantation and the long-term outcome of heart transplant recipients.

PMID- 14974522
TI  - Postoperative nursing care of the cardiac transplant recipient.
AB  - While considerable progress is being made in the medical management of heart
      failure, mortality for this disease process continues to be significant. Cardiac
      transplantation becomes the treatment of choice for those with end-stage diseases
      that are acceptable candidates. While care of the cardiac transplant patient is
      similar to those recovering from cardiopulmonary bypass after sternotomy there
      are several issues unique to the cardiac transplant recipient. These include
      cardiac denervation, allograft dysfunction, management of arrhythmias, rejection,
      immunosuppression, and infectious complications. This article provides an
      overview of the postoperative management of the cardiac transplant recipient
      while in the intensive care unit. Additionally, a brief description of the
      surgical techniques employed and the physiology related to cardiac denervation
      are presented.

PMID- 14974523
TI  - What every patient should know...pretransplantation and posttransplantation.
AB  - This article addresses an overview of patient education required for the
      postoperative heart transplant patient. The overall purpose of patient education
      is to insure the patient and, when appropriate, his or her significant other(s)
      are provided with education to enhance knowledge, skills, and behavior change.
      Patient education needs are to be continually assessed, identified, and
      addressed. Education includes instruction in the specific knowledge and skills
      needed by the patient and his or her significant other(s) to meet the patient's
      needs. Health education of the postoperative heart transplant patients may add
      significant and sustained benefits to their recovery and compliance with regime
      while reducing costs.

PMID- 14974524
TI  - The management of immunosuppression: the art and the science.
AB  - The optimal use of immunosuppressant drugs requires an understanding of their
      mechanism of action as well as a basic understanding of the biology of transplant
      rejection and tolerance. The ability to tailor a drug regimen that strikes a fine
      balance between allograft maintenance and patient well-being demands a
      sensitivity to the patient's needs and expectations as well. The object of this
      article is to cover the basic biological principles involved in selecting an
      immunosuppressant protocol while sharing our experiences with these various
      regimen.

PMID- 14974525
TI  - Sensitivity, ventricular assist devices, and the waiting game in heart
      transplantation: what's new?
AB  - Orthotopic heart transplantation became more successful with the introduction of
      cyclosporine in the late 1970s. Although congestive heart failure has become a
      significant public health issue and the proportion of patients with advanced
      heart failure has increased, the number of heart transplants performed has not
      increased substantially in the past decade. Transplant waiting times have been
      related to many different factors. Unfortunately, implantation of ventricular
      assist devices (VADS) may provoke antibody responses. These result in the
      sensitization of patients and increased waiting time prior to transplantation.
      The purpose of this article is to explore etiologies of waiting times for pre
      heart transplant and left ventricular assist device pre heart transplant
      candidates, explain new theories of sensitization, define current methods to
      detect sensitization, and discuss nursing care implications.

PMID- 14974526
TI  - A ventricular assist device bridges the way to a new life.
AB  - Cardiac transplantation is a recognized and lifesaving treatment for those
      unresponsive to all other available treatments (Hosenpud JD, Bennett LE, Kech BM,
      Boucek MM, Novick RJ. The registry of the International Society for Heart and
      Lung Transplantation: eighteenth official report-2001. J Heart Lung Transplant.
      2001;20:805-815). The number of transplants performed in the United States grows
      steadily yearly with improving drugs for infection and rejection, the 2 most
      common medical complications and still the primary causes of death in long-term
      follow-up (Zugibe F, Costello J, Breithaupt M, Segalbacher J. Model organ
      description protocols for completion by transplant surgeons using organs procured
      from medical examiner cases. J Transplant Coord. 1999;9:73). Sometimes, getting
      the patient to the transplant process is in itself a struggle. As the need for
      heart transplants increase across the nation, donor hearts have not increased,
      even with more awareness in the medical community. Therefore, our struggle
      remains with keeping the patient alive, stable, and in the best position for
      transplantation when the perfect donor heart arrives. As critical care nurses, we
      see this bridge to transplantation in the form of pharmaceutical agents and/or
      mechanical assist devices (Scherr K, Jensen L, Koshal A. Mechanical circulatory
      support as a bridge to cardiac transplantation: towards the 21st century. Am J
      Crit Care. 1999;8:324-337). The patient waits patiently for a donor heart to be
      available, but is becoming weaker in the process. We wish to see those hearts
      come sooner and healthier. In truth, this in not usually seen. Sometimes the wish
      comes true, and with the help of nurses, doctors, ancillary departments, and even
      multiple hospital systems pulling together a miracle can still happen.

PMID- 14974527
TI  - A case study in Hansen's disease acquired after heart transplant.
AB  - Hansen's disease, leprosy, is a chronic infectious disease caused by the acid
      fast bacillus Mycobacterium leprae. There are multiple forms of the disease
      ranging from the relatively benign to the progressive, malignant lepromatous
      leprosy. There is effective antimicrobial treatment available that is capable of
      curing the disease. We report the case of a post heart transplant patient
      acquiring Hansen's disease.

PMID- 14974528
TI  - Depression and anxiety in the heart transplant patient: a case study.
AB  - Depression and anxiety are potential psychological problems that a heart
      transplant patient may face both before and after transplant. In addition, there
      is the potential for difficulty in adjusting to life after transplantation.
      Anxiety and depression and their effects, both pretransplant and posttransplant,
      are explored. A case study is used to illustrate the psychological effects of
      trans plantation.

PMID- 14974529
TI  - Osteoporosis: The dynamic relationship between magnesium and bone mineral density
      in the heart transplant patient.
AB  - Osteoporosis is a common, and potentially severe, complication seen in the heart
      transplant recipient. Frequently there is loss of bone mineral density prior to
      transplant that begins the downward spiral to fractures of the femoral neck and
      vertebrae. Multiple factors are responsible for the development of osteoporosis
      posttransplant. These factors include pretransplant bone mineral loss, use of
      corticosteroids and cyclosporine posttransplant, and development of persistent
      hypomagnesemia posttransplant. This article explores the relationship of serum
      magnesium levels to maintenance of bone mineral density.

PMID- 14974530
TI  - Comparison of methods for handling censored records in beef fertility data:
      simulation study.
AB  - A simulation study was conducted to compare methods for handling censored records
      for days to calving in beef cattle data. Days to calving was defined as the time,
      in days, between when a bull is turned out in the pasture and the subsequent
      parturition. Simulated data were generated to have data structure and genetic
      relationships similar to an available field data set. Records were simulated for
      33,176 daughters of 4,238 sires. Data were simulated using a mixed linear model
      that included the fixed effects of contemporary group and sex of calf, linear and
      quadratic covariates for age at mating, and random effects of animal and residual
      error. Two methods for handling censored records were evaluated, and two
      censoring rates of 12 and 20% were applied to assess the influence of higher
      censoring rates on inferences. Censored records were assigned penalty values on a
      within-contemporary group basis under the first method (DCPEN). Under the second
      method (DCSIM), censored records were drawn from their respective predictive
      distributions. A Bayesian approach via Gibbs sampling was used to estimate
      variance components and predict breeding values. Posterior means (PM) and
      standard deviations (SD) of additive genetic variance for DCPEN at 12 and 20%
      censoring were 23.2 (3.7) and 21.0 (3.6), respectively, whereas the same
      estimates for DCSIM at 12 and 20% censoring were 23.7(3.3) and 21.9 (3.4),
      respectively. In all cases, the true value of the genetic variance was within the
      high posterior density (HPD) interval (95%). The PM (SD) of residual variance for
      DCPEN at 12 and 20% censoring were 415.7 (4.7) and 440.0 (4.8) respectively,
      whereas the same estimates for DCSIM at 12 and 20% censoring were 371.0 (4.3) and
      365.4 (4.4), respectively. The true value of the residual variance was within the
      HPD (95%) for DCSIM, but it was outside this interval for DCPEN at both censoring
      rates, indicating a systematic bias for this parameter. Bayes Factor and Deviance
      Information Criteria were used for model comparisons, and both criteria indicated
      the superiority of the DCSIM method. However, little difference was observed
      between the two methods for correlations between true breeding values and
      posterior means of animal effects for sires, indicating that no major reranking
      of sires would be expected. This finding suggests that either censored data
      handling technique can be successfully used in a genetic evaluation for days to
      calving.

PMID- 14974531
TI  - Comparison of methods for handling censored records in beef fertility data: field
      data.
AB  - The purpose of this study was to compare methods for handling censored days to
      calving records in beef cattle data, and verify results of an earlier simulation
      study. Data were records from natural service matings of 33,176 first-calf
      females in Australian Angus herds. Three methods for handling censored records
      were evaluated. Censored records (records on noncalving females) were assigned
      penalty values on a within-contemporary group basis under the first method
      (DCPEN). Under the second method (DCSIM), censored records were drawn from their
      respective predictive truncated normal distributions, whereas censored records
      were deleted under the third method (DCMISS). Data were analyzed using a mixed
      linear model that included the fixed effects of contemporary group and sex of
      calf, linear and quadratic covariates for age at mating, and random effects of
      animal and residual error. A Bayesian approach via Gibbs sampling was used to
      estimate variance components and predict breeding values. Posterior means (PM)
      (SD) of additive genetic variance for DCPEN, DCSIM, and DCMISS were 22.6d2
      (4.2d2), 26.1d2 (3.6d2), and 13.5d2 (2.9d2), respectively. The PM (SD) of
      residual variance for DCPEN, DCSIM, and DCMISS were 431.4d2 (5.0d2), 371.4d2
      (4.5d2), and 262.2d2 (3.4d2), respectively. The PM (SD) of heritability for
      DCPEN, DCSIM, and DCMISS were 0.05 (0.01), 0.07 (0.01), and 0.05 (0.01),
      respectively. Simulating trait records for noncalving females resulted in similar
      heritability to the penalty method but lower residual variance. Pearson
      correlations between posterior means of animal effects for sires with more than
      20 daughters with records were 0.99 between DCPEN and DCSIM, 0.77 between DCPEN
      and DCMISS, and 0.81 between DCSIM and DCMISS. Of the 424 sires ranked in the top
      10% and bottom 10% of sires in DCPEN, 91% and 89%, respectively, were also ranked
      in the top 10% and bottom 10% in DCSIM. Little difference was observed between
      DCPEN and DCSIM for correlations between posterior means of animal effects for
      sires, indicating that no major reranking of sires would be expected. This
      finding suggests little difference between these two censored data handling
      techniques for use in genetic evaluation of days to calving.

PMID- 14974532
TI  - Genetic evaluation of calving to first insemination using natural and artificial
      insemination mating data.
AB  - Mating and calving records for 51,084 first-parity heifers in Australian Angus
      herds were used to examine the relationship between probability of calving to
      first insemination (CFI) in artificial insemination and natural service (NS)
      mating data. Calving to first insemination was defined as a binary trait for both
      sources of data. Two Bayesian models were employed: 1) a bivariate threshold
      model with CFI in AI data regarded as a trait separate from CFI in NS data and 2)
      a univariate threshold model with CFI regarded as the same trait for both sources
      of data. Posterior means (SD) of additive variance in the bivariate analysis were
      similar: 0.049 (0.013) and 0.075 (0.021) for CFI in AI and NS data, respectively,
      indicating lack of heterogeneity for this parameter. A similar trend was observed
      for heritability in the bivariate analysis, with posterior means (SD) of 0.025
      (0.007) and 0.048 (0.012) for AI and NS data, respectively. The posterior means
      (SD) of the additive covariance and corresponding genetic correlation between the
      traits were 0.048 (0.006) and 0.821 (0.138), respectively. Differences were
      observed between posterior means for herd-year variance: 0.843 vs. 0.280 for AI
      and NS data, respectively, which may reflect the higher incidence of 100%
      conception rates within a herd-year class (extreme category problem) in AI data.
      Parameter estimates under the univariate model were close to the weighted average
      of the corresponding parameters under the bivariate model. Posterior means (SD)
      for additive, herd-year, and service sire variance and heritability under the
      univariate model were 0.063 (0.007), 0.56 (0.029), 0.131 (0.013), and 0.036
      (0.007), respectively. These results indicate that, genetically, cows with a
      higher probability of CFI when mated using AI also have a high probability of CFI
      when mated via NS. The high correlation between the two traits, along with the
      lack of heterogeneity for the additive variance, implies that a common additive
      variance could be used for AI and NS data. A single-trait analysis of CFI with
      heterogeneous variances for herd-year and service sire could be implemented. The
      low estimates of heritability indicate that response to selection for probability
      of calving to first insemination would be expected to be low.

PMID- 14974533
TI  - Genetic diversity analyses of 10 indigenous Chinese pig populations based on 20
      microsatellites.
AB  - To study the genetic diversity of Chinese indigenous pig breeds, a total of 403
      pigs from 10 local populations and 1 exotic Duroc breed were genotyped for 20
      microsatellite markers. Heterozygosity and Wright's F-statistics (F(IS), F(ST),
      and F(IT)) were calculated to determine the genetic variation in those
      populations. The observed heterozygosities were in the range of 0.31 (Duroc) to
      0.66 (Shengxian). The F(IS) value was in a range of -0.07 to 0.48. The mean F(ST)
      showed that approximately 78% of the genetic variation was within-population and
      22% was across the populations. The 10 Chinese local breeds were classified into
      two major groups according to the phylogenetic tree, which was based on standard
      genetic distance. Four pig populations, Jianli, Ganxi Two Ends Black, Shaziling,
      and Dongshan were grouped into one branch. Before the study, these four
      populations were all classified as Central China Two Ends Black according to coat
      color, shape of the head, and shape of the ear. The Jinhua pig, which also has
      the two-ends-black coat color, was also grouped to the same branch but was not
      traditionally classified into this type. The five populations were located in
      various provinces in central China. The other five populations, Nanyang Black,
      Hainan Spotted, Huainan Black, Jiaxing Black, and Shengxian Spotted (black body,
      white feet), were grouped into another branch. The two groups of pig breeds had
      the same F(ST) value (0.14) when calculated separately. This value was similar to
      that of Iberian pigs (0.13) but smaller than that of the European pigs (0.27) as
      reported by other researchers. Our study showed that large genetic
      differentiation exists in Chinese pig breeds. The grouping of the five two-ends
      black populations into one branch of the phylogenetic tree may indicate that the
      number of conservation farms can be decreased for this type of pig.

PMID- 14974534
TI  - Genetic parameters for calving difficulty, stillbirth, and birth weight for
      Hereford and Charolais at first and later parities.
AB  - The aim of this study was to estimate direct and maternal genetic parameters for
      calving difficulty score, stillbirth, and birth weight at first and later
      parities for Charolais and Hereford cattle in Sweden. Calving traits have long
      been recorded for pure-bred beef cattle in Sweden, but only birth weight has been
      used in the selection in order to avoid calving difficulties. Linear animal model
      analyses included records on birth weight for 60,309 Charolais and 30,789
      Hereford calves born from 1980 to 1999, and calving traits for 74,538 Charolais
      and 37,077 Hereford calves born from 1980 to 2001. The frequencies of difficult
      calvings and stillbirths were approximately 6% at first and 1 to 2% at later
      parities for both breeds. Fewer than half the stillborn calves were born from
      difficult calvings. Heritabilities estimated for birth weight in different
      univariate and bivariate analyses for Charolais and Hereford calves born at first
      and later parities ranged from 0.44 to 0.51 for direct effects and 0.06 to 0.15
      for maternal effects. Heritabilities on the observable scale for calving
      difficulty score of Charolais and Hereford, scored in three classes, ranged from
      0.11 to 0.16 for direct and 0.07 to 0.12 for maternal effects at first parity,
      and lower at later parities. All estimated heritabilities for stillbirth were
      very low (0.002 to 0.016 on the observable scale). Direct-maternal genetic
      correlations were negative, with few exceptions. Genetic correlations between the
      traits and between parities within traits were generally moderate to high and
      positive. Calving difficulty score should be included in the genetic evaluation
      of beef breeds in Sweden, whereas progeny groups in Swedish beef populations are
      too small for stillbirth to be considered directly.

PMID- 14974535
TI  - Identifying critical parameters in the dynamics and control of microparasite
      infection using a stochastic epidemiological model.
AB  - A stochastic epidemic model is presented to study infection transmission
      dynamics, and hence epidemic severity and disease incidence, in a closed
      population. The aim was to understand the relative importance of various
      parameters that influence the dynamics of potential epidemics, particularly when
      the genetic mechanisms of resistance or tolerance to infection are considered.
      Simulations explored the effect of varying the transmission coefficient, latent
      period, recovery period, mortality rate, and the period of loss of immunity on
      overall epidemic outcomes. The critical parameters influencing the transmission
      of infection, and hence disease incidence, were the transmission coefficient, the
      latent period, and the recovery period; the period of loss of immunity had only
      trivial effects. Ideally, control strategies should decrease the transmission
      coefficient and/or increase the latent period and/or decrease the recovery
      period. By equating measured traits with disease transmission parameters, the
      model described in this paper can be used to identify which disease resistance
      genes or QTL will be truly effective in helping to develop disease-resistant
      livestock that suffer fewer epidemics and side-effects of infection. In
      particular, emphases should be placed on finding genes that decrease the
      transmission of infection, increase the latent period, or decrease the recovery
      period.

PMID- 14974536
TI  - Effect of dietary mannanoligosaccharide and sodium chlorate on the growth
      performance, acute-phase response, and bacterial shedding of weaned pigs
      challenged with Salmonella enterica serotype Typhimurium.
AB  - A 28-d experiment evaluated the growth, acute-phase response, and bacterial
      shedding patterns in pigs (n = 96; initially 6.8 +/- 1.3 kg) fed
      mannanoligosaccharides (MANNAN) and sodium chlorate (CHLORATE) before and after
      oral challenge with Salmonella enterica serotype Typhimurium (ST). The negative
      control diet contained no antimicrobial (CON), and the positive control contained
      carbadox (CARB; 55 ppm). Test diets contained (as-fed basis) MANNAN (1,500 ppm)
      or CHLORATE (800 ppm). Pigs were fed diets for 14 d and then given ST orally.
      Pigs fed CARB had greater ADG over the entire study than pigs from other
      treatments (P < 0.05). During wk 1 to 2, before ST challenge, feed intake (as-fed
      basis) was lower for pigs fed MANNAN and CHLORATE than pigs fed CARB (P < 0.05).
      During the final 2 wk, pigs fed CARB had greater feed intake than pigs on other
      treatments (P < 0.05). Gain/feed was greater for pigs fed CARB in the 2 wk before
      ST (P < 0.05); however, in wk 3 to 4 after ST, gain/feed was reduced for CON pigs
      compared to pigs on other treatments (P < 0.05). Serum IGF-I was decreased at 2
      and 4 d after ST (P < 0.001), and, overall, IGF-I was greater in pigs fed CARB
      than CON or CHLORATE (P < 0.05). Serum haptoglobin concentrations were greater (P
      < 0.001) for all treatments at d 6 compared with d 13 after ST. Overall,
      haptoglobin was greater for MANNAN than for CARB and CHLORATE (P < 0.05) and
      tended to be increased (P < 0.06) relative to CON. Interleukin-6 was not affected
      by treatment or day post-ST challenge. Fecal shedding of salmonellae organisms
      was less for CHLORATE (P < 0.05) than all other treatments at 7 d after ST.
      Shedding scores decreased from d 7 to 14 after ST (P < 0.05) for the CON, CARB,
      and MANNAN treatments. We conclude that feeding MANNAN and CHLORATE before acute
      enteric disease challenge may support improved gut function as evidenced by
      improved gain/feed, and that CHLORATE may decrease bacterial shedding. But
      neither MANNAN nor CHLORATE enhanced growth relative to the absence of dietary
      antimicrobials, nor was either treatment as effective as CARB following ST
      challenge.

PMID- 14974537
TI  - Intermittent suckling: effects on piglet and sow performance before and after
      weaning.
AB  - An experiment was conducted to study effects of intermittent suckling on creep
      feed intake and weight gain of litters. Loss of weight and backfat during
      lactation, as well as reproductive performance, were also measured. Batches of
      multiparous sows (Parity 1 to 12, 4.1 on average) were either suckled
      intermittently (IS, eight batches; n = 50) or continuously (control, eight
      batches; n = 62). Litters were weaned at 27 +/- 2 d of age, on average. Litter
      size (11.1 +/- 0.2 piglets, on average) was standardized within a batch within 3
      d of birth. All litters had free access to creep feed and water from 1 wk of age
      onward. In the IS group, litters were separated from the sow for a period of 12
      h/d (0930 to 2130), starting 11 d before weaning. Rectal ultrasonography was
      applied at d 3 after weaning to check the ovaries for follicle development or
      presence of corpora lutea. Creep feed intake by the litters during lactation was
      higher in IS litters than in control litters (686 +/- 57 vs. 314 +/- 42 g/piglet,
      P < 0.01). The distribution of creep feed intake shifted from a skewed one, with
      a majority of litters consuming less than 250 g/piglet in control litters, to a
      normal distribution, with an average creep feed intake of 500 to 750 g/piglet in
      IS litters. During the 7 d after weaning, creep feed intake in IS litters was
      also higher (281 +/- 15 vs. 204 +/- 9 g-piglet(-1) x d(-1), P < 0.01). The ADG of
      piglets during lactation was negatively affected by IS, resulting in lower weight
      at weaning (7,229 +/- 140 vs. 7,893 +/- 145 g/piglet, P < 0.05). During the 7 d
      after weaning, however, ADG was higher in IS litters (255 +/- 10 vs. 177 +/- 8 g
      piglet-1 x d(-1), P < 0.01), and 7 d after weaning, the weights of the litters
      were similar (9,011 +/- 167 vs. 9,132 +/- 164 g/ piglet, P = 0.81). The IS
      litters that consumed little or no feed during lactation had an ADG after
      lactation that was higher than in control litters, with comparable creep feed
      intake during lactation: 204 vs. 136 g/d. Body weight loss by the sows during
      lactation was lower in IS sows (-10 +/- 2 vs. -16 +/- 1 kg, P < 0.05). A higher
      percentage of IS sows ovulated during lactation (22 vs. 3%, P < 0.01), and
      weaning-to-ovulation interval (excluding sows with lactational ovulation) was
      shorter in IS sows (4.7 +/- 0.2 vs. 5.3 +/- 0.2 d, P < 0.05). We conclude that IS
      increased creep feed intake during lactation, and that IS increased ADG after
      weaning, despite lower weaning weights. Ovulation during lactation was induced in
      22% of the IS sows.

PMID- 14974538
TI  - Within-litter variation in muscle fiber characteristics, pig performance, and
      meat quality traits.
AB  - The objective of this study was to examine the intralitter variation in postnatal
      growth performance, meat quality, and muscle fiber characteristics when
      littermates were categorized by carcass weight. Thirty-nine litters were weaned
      at 4 wk of age and had free access to feed from 2 wk of age until slaughter. They
      were slaughtered by litter at an average BW of 104 +/- 14 kg, and six pigs per
      litter were selected for analysis: the heaviest- (HW), middle- (MW), and lightest
      weight (LW) pig of each sex. Categorizing littermates in LW, MW, and HW pigs at
      the same age reflected the differences in postnatal growth rate within a litter;
      thus ADG, muscle mass, and muscle deposition rate differed across pig weight
      groups (P < 0.001). Also, the total DNA content was different among pig weight
      groups (P < 0.001) and reflected differences in muscle growth rate. The
      difference in muscle growth rate between LW and MW pigs could be explained by a
      larger (P < 0.05) mean fiber area (MFA) in MW pigs, whereas the number of muscle
      fibers was similar. Growth rate differences between MW and HW pigs could in part
      be explained by a higher number (P < 0.01) of equal-sized muscle fibers in HW
      pigs. The difference in MFA was due to a higher estimated DNA and RNA content per
      muscle fiber in MW and HW compared with LW pigs (P < 0.05). Pigment content was
      higher in MW and HW compared with LW pigs (P < 0.01), but no other measured meat
      quality traits were significantly different across pig weight groups. These
      results indicate that both the number and the growth rate of muscle fibers
      contribute to intralitter variation in postnatal growth performance.

PMID- 14974539
TI  - Effects of birth weight and postnatal nutrition on neonatal sheep: IV. Organ
      growth.
AB  - This study investigated effects of birth weight and postnatal nutrition on organ
      growth in neonatal lambs. Suffolk x (Finnsheep x Dorset) low- (mean +/- SD 2.29
      +/- 0.34 kg, n = 28) and high- (4.84 +/- 0.45 kg, n = 20) birth-weight male lambs
      were studied. Lambs within each birth weight category were allocated to be
      individually grown rapidly (ad libitum fed, ADG 337 g, n = 20) or slowly (ADG 150
      g, n = 20) on a liquid diet to live weights up to approximately 20 kg. All organs
      weighed less at birth in small than in large newborns (P < 0.001), except the
      adrenals (P = 0.10). At birth, as a percentage of empty body weight (EBW), small
      newborns had larger testes (0.14 vs. 0.10%, P = 0.023) and smaller thymus (0.17
      vs. 0.37%, P = 0.009), and tended to have a larger heart (0.85 vs. 0.75%, P =
      0.060) and a smaller spleen (0.10 vs. 0.14%, P = 0.054) than large newborns.
      During the first 2 to 3 wk postpartum, small newborns had greater fractional
      growth rates of organs than large newborns, most notably spleen, thymus, and
      liver. Postnatal growth of organs was more closely associated with EBW than age,
      except for lungs, testes, and stomach. At completion of rearing to 20 kg of live
      weight, small newborns had a spleen approximately 30% heavier than large newborns
      (P < 0.001). Testes weights were 37% and 24% greater in small newborns reared
      slowly and rapidly, respectively, compared with their high-birth-weight
      counterparts (P = 0.034). It was also evident that postnatal nutrition altered
      the mass of individual organs at the conclusion of the rearing period without
      affecting the combined weight of dissected organs. Slowly reared lambs had a
      larger pancreas (+27%, P = 0.002), stomach complex (+83%, P < 0.001), large
      intestine (+39%, P < 0.001), entire gastrointestinal tract (+18%, P = 0.002), and
      testes (+54%, P = 0.016) and tended to have a larger heart (+6%, P = 0.068) than
      their rapidly reared counterparts at 20 kg of live weight. Rapidly reared lambs
      had a larger thymus (+61%, P = 0.003), liver (+34%, P < 0.001), kidneys (+33%, P
      < 0.001), and small intestine (+17%, P < 0.001) and tended to have a larger
      thyroid (+13%, P = 0.054) at 20 kg of live weight than slowly reared lambs. The
      functional significance of the smaller thymus at birth and increase in spleen and
      testes weights at 20 kg of live weight in low- compared with high-birth-weight
      lambs warrants further investigation. It also remains to be established whether
      these differences at 20 kg of live weight persist.

PMID- 14974540
TI  - Recruitment and differentiation of intramuscular preadipocytes in stromal
      vascular cell cultures derived from neonatal pig semitendinosus muscles.
AB  - The present study examined the influence of dexamethasone (DEX) treatment on
      preadipocyte recruitment and expression of CCAAT/enhancing binding protein-alpha
      (C/EBPalpha) and peroxisome proliferator-activated receptor-gamma (PPARgamma)
      proteins in stromal-vascular (SV) cell cultures derived from neonatal
      subcutaneous adipose tissue and semitendinosus muscles. One adipose tissue SV
      cell culture and one semitendinosus muscle SV cell culture were established from
      each of six young pigs (5 to 7 d of age). Conventional SV cell-culture procedures
      were used to digest adipose and muscle tissue and to harvest and culture adipose
      and muscle SV cells. Muscles were digested after the removal of all visible
      connective tissue from the excised muscle. One hour after seeding, muscle SV cell
      cultures were rinsed and refed new media to remove debris and insoluble muscle
      protein. The SV cell cultures were double-stained for lipid and the AD-3
      antibody, a preadipocyte marker, at 1, 3, and 6 d and were double-stained for
      lipid and C/EBPalpha or PPARgamma at d 6. Preadipocytes were randomly distributed
      and not clustered after 1 d in muscle and adipose SV cultures. Regardless of
      treatment, relative and absolute fat cell numbers were lower (P < 0.05) in muscle
      than in adipose-SV cell cultures. The DEX treatments produced similar magnitudes
      of increase in relative and absolute preadipocytes and adipocytes in muscle- and
      adipose-SV cultures. Several extracellular matrix substrata had no influence on
      adipogenesis in muscle-SV cell cultures. These studies indicate that muscle-SV
      cultures are characterized by a low number of adipocytes under basal conditions
      and a low number of glucocorticoid-responsive preadipocytes.

PMID- 14974541
TI  - Plasma hormones and metabolites in Piedmontese cows during late pregnancy:
      relationships with calf birth weight.
AB  - Relationships among plasma hormonal and metabolic variables in the last trimester
      of gestation in 59 Piedmontese dams (n = 15 heifers, n = 44 cows) and the calf
      birth weight (BWT) class of their offspring were investigated in seven herds. The
      BWT data were categorized as follows: > 50 kg (BWT-A), 46 to 50 kg (BWT-B), 41 to
      45 kg (BWT-C), and < 41 kg (BWT-D). Blood samples were collected at 33, 36, and
      39 wk of gestation. Packed cell volume (PCV) and plasma concentrations of
      insulin, estrone sulfate (E1SO4), NEFA, and creatinine were determined and
      correlated to BWT class. Creatinine: E1SO4 ratio also was calculated. Duration of
      gestation was greater for dams producing a BWT-A calf than for the other BWT
      classes, and calf BWT was heavier (P < 0.001) for calves in the BWT-A vs. BWT-D
      class. The heaviest calf in BWT-A was associated with the highest calving
      difficulty score. Insulin and PCV values were not affected by week of gestation,
      whereas plasma E1SO4, NEFA, and creatinine content increased (P < 0.001) and
      creatinine:E1SO4 decreased (P < 0.001) during late gestation. Calf BWT class did
      not affect PCV value. Plasma E1SO4 concentrations were lower (P < 0.01) in BWT-D
      dams than the other dams, showing the greatest difference at 39 wk of gestation.
      At 36 and 39 wk of gestation, dams bearing BWT-C and BWT-D calves had a higher (P
      < 0.01) plasma insulin concentration than those bearing BWT-A and BWT-B calves.
      Plasma NEFA concentrations at 39 wk of gestation were higher (P < 0.05) in dams
      of calf BWT-A than in the other dams. We conclude that plasma E1SO4 level is a
      variable that can be used to monitor problems related to a small size calf.
      Conversely, the forthcoming birth of a calf with a heavy BW seems to be preceded
      by a pronounced increase in plasma NEFA level in the dam just a few days before
      calving.

PMID- 14974542
TI  - Plasma concentrations of leptin, insulin-like growth factor-I, and insulin in
      relation to changes in body condition score in heifers.
AB  - The objective of this study was to determine the relationships among plasma
      concentrations of leptin, insulin, and IGF-I with dynamic changes in body
      condition scores (BCS) in heifers. Nineteen Zebu-Brown Swiss crossbred heifers,
      24 to 30 mo old, weighing 322 +/- 9 kg, and with an initial BCS of 2.6 +/- 0.11
      (range = 1 to 9) were used. Heifers were fed 60% of their maintenance
      requirements until they reached a BCS of < or = 2. Heifers were then maintained
      at that level for 25 d, after which they were fed to gain 1 kg of body weight
      daily until a BCS of 6 was reached. Heifers were weighed weekly and BCS was
      measured every 2 wk. Plasma samples were collected twice weekly, and leptin and
      insulin were determined by RIA. An immunoradiometric assay was used to measure
      IGF-I from one sample every 2 wk. Plasma concentrations of leptin were positively
      correlated during nutritional restriction (NR) and weight gain (WG) periods with
      BCS (r = 0.47 for NR, and r = 0.83 for WG; P < 0.01) and body weight (r = 0.40
      for NR, and r = 0.78 for WG; P < 0.01). Plasma concentrations of leptin decreased
      during nutritional restriction (P < 0.01) as BCS decreased. During weight gain,
      leptin concentration increased at BCS 3 and thereafter for each integer change in
      the BCS. Regression analysis showed that changes in body weight affect leptin
      concentrations within a given BCS. There was a decrease in IGF-I as BCS declined
      (P < 0.01). During weight gain, by contrast, IGF-I increased significantly (P <
      0.01) with every unit change in body condition up to BCS of 4 and plateaued
      thereafter. Insulin concentrations did not change during nutritional restriction
      when BCS decreased from 3 to 1. However, once the diet was improved, there was a
      large increase in insulin concentrations in heifers with BCS 1 (P < 0.01). Among
      heifers of BCS 2 and 3, insulin did not differ and was lower than in heifers of
      BCS 1 (P < 0.01). Insulin increased (P < 0.01) among heifers at BCS 4 to 6.
      Leptin was positively correlated (P < 0.01) with both IGF-I (r = 0.34 for NR, and
      r = 0.36 for WG) and insulin (r = 0.18 for WG). Insulin was correlated with IGF-I
      (r = 0.60; P < 0.01). During nutritional restriction, insulin did not correlate
      with leptin (r = -0.05), BCS (r = -0.03), or IGF-I (r = 0.07). It was concluded
      that leptin serves as a dynamic indicator of body condition in heifers, as well
      as an indicator of nutritional status.

PMID- 14974543
TI  - The relationship of porcine sperm zona-binding ability to fertility.
AB  - Several laboratory assays have been designed to assess the fertility potential of
      a semen sample before insemination, but none have been consistent and accurate
      predictors of fertility. To determine whether zona-binding ability may be a
      useful fertility predictor, we validated and used an in vitro competitive assay
      to measure the ability of porcine sperm to bind to the zona pellucida. The zona
      binding ability of sperm from 11 boars that exhibited a broad range in average
      litter size and farrowing rate was determined. Sperm from each boar were compared
      directly with sperm from eight other boars in a systematic, pairwise fashion.
      Sperm from two semen samples were labeled with fluorophores at concentrations
      that did not affect motility or zona-binding ability. An equal number of labeled
      sperm from each boar was coincubated with homologous oocytes. Least squares means
      from analysis of variance were used to rank boars based on zona-binding ability.
      The competitive assay was effective in establishing a ranking of the boars (R2 =
      0.62). Furthermore, there was a correlation between zona-binding ability and
      fertility when estimated by average litter size (r = 0.64, P < 0.05) but not when
      estimated by farrowing rate (r = -0.28). The explanation for this difference was
      that litter size and farrowing rate were poorly correlated (r = 0.14). In
      conclusion, a competitive zona-binding assay distinguished boars that sired
      either small or large litters. Competitive zona-binding ability may be useful for
      identifying boars with reduced fertility that produce smaller litters following
      insemination.

PMID- 14974544
TI  - Ovarian follicular development in cattle selected for twin ovulations and births.
AB  - Comparisons of numbers of antral ovarian follicles and corpora lutea (CL), of
      blood hormone concentrations, and of follicular fluid steroid concentrations and
      IGFBP activity were conducted between cows selected (twinner) and unselected
      (control) for twin births to elucidate genetic differences in the regulation of
      ovarian follicular development. Ovarian follicular development was synchronized
      among cows by a single i.m. injection of PGF2alpha on d 18 of the estrous cycle;
      six cows per population were slaughtered at 0, 24, 48, and 72 h after PGF2alpha.
      Jugular vein blood was collected from each animal at PGF2alpha injection and at
      24-h intervals until slaughter. Ovaries of twinner cows contained more small (<
      or = 5 mm in diameter, P < 0.05), medium (5.1 to 9.9 mm, P < 0.05), and large (>
      or = 10.0 mm, P < 0.01) follicles and more (P < 0.01) CL than ovaries of
      controls. Follicular fluid concentrations of estradiol, androstenedione,
      testosterone, and progesterone reflected the stage of follicular development and
      were similar for twinner and control follicles at the same stage. Earlier
      initiation of follicular development and/or selection of twin-dominant follicles
      in some twinner cows resulted in greater concentrations of estradiol in plasma at
      0, 24, and 48 h and of estradiol, androstenedione, and testosterone in follicular
      fluid of large follicles at 0 h after PGF2alpha for twinner vs. control cows
      (follicular status x time x population, P < 0.01). Binding activities of IGFBP-5
      and -4 were absent or reduced (P < 0.01) in follicular fluid of developing medium
      and large estro-gen-active (estradiol:progesterone ratio > 1) follicles but
      increased with atresia. Only preovulatory Graafian follicles lacked IGFBP-2
      binding, suggesting a possible role for IGFBP-2 in selection of the dominant
      follicle. Concentrations of IGF-I were twofold greater (P < 0.01), but GH (P =
      0.10) and cholesterol (P < 0.05) were less in blood of twinners. Three
      generations of selection of cattle for twin ovulations and births enhanced
      ovarian follicular development as manifested by increased numbers of follicles
      within a follicular wave and subsequent selection of twin dominant follicles.
      Because gonadotropin secretion and ovarian steroidogenesis were similar for
      control and twinner cattle, enhanced follicular development in twinners may
      result from decreased inhibition by the dominant follicle(s), increased ovarian
      sensitivity to gonadotropins, and/or increased intragonadal stimulation, possibly
      by increased IGF-I.

PMID- 14974545
TI  - Lack of an association between plasma follicle-stimulating hormone concentrations
      and ovarian weight in prepubertal gilts.
AB  - Selection for increased number of corpora lutea in gilts is associated with
      increased plasma FSH concentrations during pubertal development. In the current
      study, 270 gilts from a control (CO) line and a line selected for increased
      ovulation rate (OR) were unilaterally ovariectomized at 85 d of age, and this
      ovarian weight was related to FSH concentrations at 65, 75, and 85 d of age.
      Gilts were produced during two farrowing seasons, spring and fall, and the age at
      first estrus was monitored from 160 to 250 d. Plasma FSH was greater in OR than
      in CO gilts at 65 (P < 0.01) and 75 d (difference in spring greater than in fall,
      P < 0.01), but FSH at these ages was not correlated with ovarian weight at 85 d.
      At 85 d, FSH did not differ in gilts of these lines; however, FSH was negatively
      correlated (r = -0.27, P < 0.01) with ovarian weight. The proportion of gilts
      detected in estrus was less for spring-born CO gilts than for spring-born OR or
      for fall-born CO and OR gilts (78 vs. 92%, season x line, P < 0.02). The age at
      first estrus was similar in the two lines but was earlier (P < 0.01) for spring
      born than for fall-born gilts (194 vs. 204 d). Concentrations of FSH at each of
      the ages examined were not correlated with the age at first estrus. These
      observations support the conclusion that selection for a greater number of
      corpora lutea produces a correlated increase in plasma FSH during early pubertal
      development. This increase in FSH most likely reflects differences in FSH
      synthesis and release and not differences in the stage of pubertal development.

PMID- 14974546
TI  - Oxidation of glucose, glutamate, and glutamine by isolated ovine enterocytes in
      vitro is decreased by the presence of other metabolic fuels.
AB  - The objective of this study was to evaluate oxidative metabolism of glucose,
      glutamate, and glutamine by isolated ovine enterocytes in the presence of other
      metabolic fuels in vitro. A mixed mucosal primary cell culture containing
      enterocytes was isolated from crossbred wether sheep (n = 6) fed a mixed forage
      concentrate diet and incubated for 90 min with 1 mM U-14C-glucose, -glutamate, or
      -glutamine and additional substrates (water as negative control, acetate,
      propionate, butyrate, glucose, glutamate, or glutamine) at concentrations of 0.1,
      1.0, and 10.0 mM. Oxidation of labeled substrates to CO2 and net production of
      lactate and pyruvate in incubation media were measured. Oxidation of glucose and
      glutamine to CO2 was decreased (P < 0.05) by 5 to 40% in the presence of
      additional substrates except acetate. Our observation that glutamine oxidation
      can be decreased by the presence of additional substrates is contrary to
      observations in the literature using enterocytes from nonruminants, indicating
      that ruminant enterocytes might rely on glutamine to a lesser extent as an energy
      source. Net glucose utilization was decreased (P < 0.05) 16% by propionate (10
      mM) compared with control but was not affected by the other additional
      substrates. Glutamate oxidation to CO2 was decreased 28% (P < 0.05) in the
      presence of propionate (10 mM) or by 17 and 33% in the presence of glutamine (1.0
      and 10 mM, respectively), but not by that of the other additional substrates.
      Acetate did not affect the oxidation of glucose, glutamate, and glutamine.
      Propionate decreased (P < 0.05) the oxidation of glucose and glutamate only at
      the highest concentration (10 mM), indicating that the sparing effects of
      propionate on substrate oxidation are affected by its concentration in the
      incubation media. These observations indicate that ruminant enterocytes possess
      metabolic flexibility for oxidative metabolism of glucose, glutamine, and
      glutamate depending on the type and concentration of available additional
      substrates.

PMID- 14974547
TI  - Effect of forage quality on digestion and performance responses of cattle to
      supplementation with cooked molasses blocks.
AB  - We evaluated the effect of forage quality on response of cattle to
      supplementation with cooked molasses blocks. In Exp. 1, 175 heifers had ad
      libitum access to prairie hay (5.2% CP, DM basis). Treatments were a 2 x 3
      factorial: supplementation with 0 or 1.96 kg/d of alfalfa DM, and supplementation
      with no cooked molasses block or with a low-protein or a high-protein cooked
      molasses block (14.4 and 27.5% CP, respectively, DM basis). There were no
      significant interactions between alfalfa and cooked molasses block for intake or
      gain. Forage intake and ADG were increased (P < 0.05) by alfalfa supplementation.
      Heifers fed high-protein cooked molasses blocks gained more (P < 0.05) weight
      than those fed low-protein cooked molasses blocks or no cooked molasses block.
      Heifers fed high-protein cooked molasses blocks ate more (P < 0.05) forage than
      those fed low-protein cooked molasses blocks, with heifers fed no cooked molasses
      block being intermediate. In Exp. 2, responses to cooked molasses blocks
      containing 33% CP (DM basis) were measured in 18 steers fed: 1) brome (8.4% CP),
      2) alfalfa (19.2% CP), or 3) brome supplemented with 1.93 kg/d of alfalfa DM.
      Forages were available ad libitum. Forage DM intake was not affected by cooked
      molasses block and was greater (P < 0.05) for alfalfa than the alfalfa/brome mix,
      which in turn was greater (P < 0.05) than brome. Digestibility of DM was greater
      (P < 0.05) for alfalfa than brome or the alfalfa/brome mix and was not affected
      by cooked molasses block supplementation. Supplementation with cooked molasses
      blocks had only small effects on intake and digestion of medium- to high-quality
      forages, but it improved gains and feed efficiencies of heifers fed prairie hay
      ad libitum, with or without supplemental alfalfa.

PMID- 14974548
TI  - Nitrogen balance in lambs fed a high-concentrate diet and infused with differing
      proportions of casein in the rumen and abomasum.
AB  - Twenty-five wether lambs (34 +/- 0.9 kg) fitted with ruminal and abomasal
      infusion catheters were used in a completely randomized design to determine the
      effects of differing proportions of ruminal and abomasal casein infusion on N
      balance in lambs fed a high-concentrate diet (85% corn grain, 1.6% N; DM basis)
      for ad libitum intake. Wethers were infused with 0 (control) or 10.4 g/d of N
      from casein with ruminal:abomasal infusion ratios of 100:0, 67:33, 33:67, or
      0:100% over a 14-d period. Feed, orts, feces, and urine were collected over the
      last 5 d. Total N intake and excretion were greater (P < 0.01) in lambs infused
      with casein than in controls; however, N retention did not differ in lambs
      infused with casein compared with controls, suggesting that N requirements were
      met without casein supplementation. Total N intake and total N excretion did not
      differ among casein infusion treatments. Urinary N excretion decreased linearly
      (P = 0.07) with decreasing ruminal infusion of casein. Site of casein infusion
      quadratically (P = 0.06) influenced N retained (g/d), with the greatest retention
      observed in the 33:67 ruminal:abomasal infusion treatment. Dry matter intake from
      feed decreased from 1,183 to 945 g/d (P = 0.02) in lambs infused with casein
      compared with controls, but apparently digested DM did not differ among
      treatments. These data indicate that decreasing the ruminal degradability of
      supplemental protein above that required to maximize N retention results in
      decreased urinary excretion of N without greatly affecting apparent diet
      digestion.

PMID- 14974549
TI  - Nitrogen balance in lambs fed low-quality brome hay and infused with differing
      proportions of casein in the rumen and abomasum.
AB  - Twenty wether lambs (46 +/- 2 kg) fitted with ruminal and abomasal infusion
      catheters were used in a completely randomized design to determine the effects of
      differing proportions of ruminal and abomasal casein infusion on N balance in
      lambs fed low-quality brome hay (0.8% N, DM basis) for ad libitum intake. Wethers
      were infused with 0 (control) or 10.7 g/d of N from casein with ratios of
      ruminal:abomasal infusion of 100:0 (100R:0A), 67:33 (67R:33A), 33:67 (33R:67A),
      or 0:100% (0R:100A), respectively, over a 12-d period. Total N supply (hay N
      intake + N from casein infusion) was greater (P = 0.001) in lambs receiving
      casein infusion than in controls. Urinary N excretion (g/d) was greater (P =
      0.001) in lambs receiving casein infusion than in controls. Urinary N excretion
      decreased as casein infusion was shifted from 100R:0A to 33R:67A and then
      slightly increased in lambs receiving 0R:100A (quadratic, P = 0.02). Total N
      excretion was greater (P = 0.001) in lambs receiving casein infusion than in
      controls and decreased linearly (P = 0.005) as casein infusion was shifted to the
      abomasum. Retained N (g/d, % of N intake, and % of digested N) was greater (P =
      0.001) in lambs receiving casein than in controls. Retained N increased as
      infusion was shifted from 100R:0A to 33R:67A and then slightly decreased in lambs
      receiving 0R: 100A (quadratic, P < 0.07). Based on regression analysis, the
      predicted optimum proportion of casein infusion to maximize N retention was 68%
      into the abomasum. The regression suggests that supplementation with undegradable
      intake protein had an additional benefit over supplementation with ruminally
      degradable intake protein (100R:0A) and that changing the percentage of ruminally
      undegradable intake protein in supplemental protein from 33 to 100% resulted in
      minimal differences in N retention. Apparent N, DM, OM, and energy digestibility
      (% of intake) was greater (P < 0.03) in lambs infused with casein than controls
      but did not differ among casein infusion groups. These data suggest that feeding
      protein supplements containing a portion (greater than 0%) of the crude protein
      as ruminally undegradable intake protein, as compared to 100% ruminally
      degradable intake protein, to lambs consuming low-quality forage increases N
      retention and the efficiency of N utilization without influencing total-tract
      nutrient digestion.

PMID- 14974550
TI  - Flow paths of plant tissue residues and digesta through gastrointestinal segments
      in Spanish goats and methodological considerations.
AB  - A sequence of eight twice-daily meals, each marked with different rare earth
      elements, was fed to 24 Spanish goats (BW = 20.6 +/- 1.94 kg) to produce meal
      based profiles of rare earth markers within segments of the gastrointestinal
      digesta on subsequent slaughter. Accumulative mean residence time and time delay
      of rare earths and segmental and accumulative mean residence times of
      indigestible NDF (IDF) were estimated for each sampled segment. Diets consisted
      of ad libitum access to bermudagrass hay with a limit feeding of one of four
      supplements: 1) minerals (basal, B); 2) B + energy (E); 3) B + CP (CP); or 4) B +
      E + CP for 84 d. Mean daily intake (g/kg of BW) during the 5 d before slaughter
      differed (P < 0.05) via diet for DM but not for IDF (8.0 +/- 0.35 g/kg of BW).
      Larger estimates of cumulative mean residence time for IDF vs. rare earths were
      suggested to be the consequence of a meal-induced bias in the single measurement
      of IDF pool size by anatomical site. The rare earth compartment method was
      considered more reliable than the IDF pool dilution method because it yielded
      flow estimates based on the flux of eight meal-dosed rare earth markers over 4 d
      and was independent of anatomical definitions of pool size. Statistically
      indistinguishable estimates for gastrointestinal mean residence times for IDF and
      rare earths conform to assumed indelibility for the specifically applied rare
      earths and indigestibility of IDF. The potentially digestible NDF (PDF):IDF ratio
      of dietary fragments (0.8) progressively decreased in the following order:
      caudodorsal reticulorumen (0.390) > crainodorsal reticulorumen (0.357)
      approximately reticulum (0.354) > mid-dorsal reticulorumen (0.291) approximately
      ventral reticulorumen (0.286), to that within the omasal folds and in the
      abomasum (0.259). Such a gradient of progressively aging mixture of plant tissue
      fragments is consistent with age-dependent flow paths established in the
      reticulorumen and flowing to the omasum and abomasum. Such heterogeneity of
      fragment ages within the reticulorumen is also indicated by the superior fit of
      marker dose site double dagger marker sampling site model assumptions.
      Additionally, cyclic meal- and rumination-induced variations in escape rate
      occur. Estimates of mean escape rates over days, needed for the practice of
      ruminant nutrition, must consider the complex interactions among plant tissues
      and the dynamics of their ruminal digestion of PDF.

PMID- 14974551
TI  - Evaluating consumer acceptability of various muscles from the beef chuck and rib.
AB  - One hundred thirty-eight consumers evaluated steaks from the complexus (CX),
      infraspinatus (IF), serratus ventralis (SV), supraspinatus (SS), and triceps
      brachii (TB) from the wholesale beef chuck; the deep pectoral (DP) from the
      wholesale brisket; and the longissimus thoracis (LT) from the wholesale rib. The
      LT was used as a reference for comparison to the other muscles. Ten USDA Choice
      and ten USDA Select boneless boxed beef subprimals were used for each muscle.
      Subprimals were aged 14 d from box date, frozen, and cut into 2.5-cm-thick
      steaks. Consumers rated the IF highest (P < 0.05) for overall like, tenderness,
      juiciness, and flavor, and assigned it the highest (P < 0.05) price/0.45 kg. The
      TB also was rated higher (P < 0.05) than the LT for overall like, tenderness,
      juiciness, flavor, and price/0.45 kg. The SV and CX were rated as being similar
      (P < 0.05) to the LT for overall like, tenderness, juiciness, flavor, and
      price/0.45 kg. Consumers rated the SS lower (P < 0.05) than the LT for
      tenderness, juiciness, flavor, and price. The DP was rated as the toughest,
      driest, and blandest (P < 0.05), resulting in assignment of the lowest (P < 0.05)
      price/0.45 kg. Differences in palatability ratings due to quality grade were
      found for several muscles; USDA Choice SV and SS were rated higher (P < 0.05) for
      overall like, tenderness, and juiciness than USDA Select SV and SS. For the IF,
      USDA Choice was rated higher (P < 0.05) for tenderness and juiciness than USDA
      Select. The USDA Choice TB was rated higher (P < 0.05) for juiciness, and the
      USDA Choice DP was rated higher (P < 0.05) for overall like, than their USDA
      Select counterparts. Tenderness, juiciness, and flavor ratings were correlated
      with overall like ratings (r = 0.84, 0.77, and 0.76, respectively) and with price
      (r = 0.73, 0.70, and 0.68, respectively). These results indicate the IF, TB, SV,
      and CX were acceptable, whereas and the SS and DP were unacceptable as steaks.

PMID- 14974552
TI  - The effects of gender and slaughter weight on the growth performance, carcass
      traits, and meat quality characteristics of heavy pigs.
AB  - Crossbred pigs (n = 192) from Pietrain x Large White sires mated to Landrace x
      Large White dams, with a mean BW of 75 +/- 1.3 kg, were used to investigate the
      effects of gender and slaughter weight (SW) on growth performance, carcass
      characteristics, and meat quality. Pens of pigs (eight pigs/pen) were assigned
      randomly to one of six treatments arranged in a 2 x 3 factorial design with two
      genders (barrows or gilts) and three SW (116, 124, or 133 kg). Each treatment was
      replicated four times. Over the entire trial, barrows had higher (P < 0.001) ADFI
      (as-fed basis) and ADG than gilts; however, gilts had higher (P < 0.05) gain-to
      feed ratios (G:F) than barrows. Barrows had lower (P < 0.01) dressing percents
      than gilts and produced fatter (P < 0.001) carcasses that had lower trimmed
      shoulder (P < 0.10) and ham (P < 0.001) yields than gilts. There was a trend for
      the semimembranosus muscle (SM) from barrows to have a higher (P < 0.10) 45-min
      pH than that of gilts, but 24-h pH was 0.11 pH unit higher (P < 0.01) in the SM
      of barrows than gilts. Gender had no (P > 0.10) effect on the moisture and lipid
      content of the longissimus muscle (LM), nor did gender affect (P > 0.10) LM
      color, myoglobin content, or thaw loss percentage. However, the LM from barrows
      had lower (P < 0.05) cooking loss percentages and tended to have lower (P < 0.10)
      shear force values than the LM from gilts. Pigs slaughtered at 116 kg had higher
      (P < 0.05) ADG than pigs slaughtered at 124 and 133 kg. Daily feed intake (as-fed
      basis) was not (P > 0.10) different among SW; however, pigs slaughtered at 116
      and 124 kg had higher (P < 0.001) G:F than those slaughtered at 133 kg. Dressing
      percent, backfat depth, carcass length, and ham and shoulder weights increased (P
      < 0.001) as SW increased from 116 to 133 kg. The initial (45-min) pH of the SM
      from pigs slaughtered at 133 kg was higher (P < 0.05) than from pigs slaughtered
      at 116 or 124 kg; however, 24-h pH was not (P > 0.10) affected by SW. The LM from
      pigs slaughtered at 133 kg was darker (lower L* values; P < 0.001), redder
      (higher a* value; P < 0.01), and had more (P < 0.001) myoglobin than the LM of
      pigs slaughtered at 116 and 124 kg. Barrows and gilts of this particular
      crossbreed can be used to produce acceptable quality fresh pork when slaughtered
      at 116 kg; however, increasing SW to 124 kg, or more, decreased live pig
      performance and carcass leanness without any additional benefits to pork quality
      attributes.

PMID- 14974553
TI  - Variation in palatability and biochemical traits within and among eleven beef
      muscles.
AB  - The objective of this study was to determine the extent of variation in, and
      relationships among, biochemical and palatability traits within and among 11
      major beef muscles. Longissimus thoracis et lumborum (LD), psoas major (PM),
      gluteus medius (GM), semimembranosus (SM), adductor (AD), biceps femoris (BF),
      semitendinosus (ST), rectus femoris (RF), triceps brachii (TB), infraspinatus
      (IS), and supraspinatus (SS) from one side of 31 Charolais x MARC III steer
      carcasses were vacuum-packaged, stored at 2 degrees C until 14 d postmortem, and
      then frozen at -30 degrees C. The 2.54-cm-thick steaks were obtained from two or
      three locations within muscles in order to assess biochemical traits and Warner
      Bratzler shear force, and from near the center for sensory trait evaluation. The
      PM was most tender and was followed by IS in both shear force and tenderness
      rating (P < 0.05). The other muscles were not ranked the same by shear force and
      tenderness rating. The BF had the lowest (P < 0.05) tenderness rating. The PM,
      GM, and LD had lower (P < 0.05) collagen concentration (2.7 to 4.5 mg/g muscle)
      than muscles from the chuck and round (5.9 to 9.0 mg/g), except for the AD (4.9
      mg/g). Desmin proteolysis was highest (P < 0.05) for BF and LD (60.7 and 60.1%
      degraded), and was lowest (P < 0.05) for PM (20.2%). The PM, TB, IS, RF, and ST
      had relatively long sarcomere lengths (> 2.1 microm), whereas the GM had the
      shortest (P < 0.05) sarcomere length (1.7 microm). Cooking loss was lowest (P <
      0.05) for BF (18.7%) and was followed by LD and IS (20.7%); it was highest (P <
      0.05) for ST (27.4%). Across all muscles, tenderness rating was highly correlated
      (r > 0.60) with shear force, connective tissue rating, sarcomere length, and
      collagen content. Within a muscle, correlations among all traits were generally
      highest in LD and lowest in AD. Within muscle, location effects were detected (P
      < 0.05) for shear force (PM, ST, BF, SM, and RF), sarcomere length (PM, ST, BF,
      LD, SS, IS, SM, and RF), collagen concentration (PM, BF, SS, IS, SM. AD, TB, and
      RF), desmin degradation (PM, GM, BF, SM, AD, and, RF), and cooking loss (all
      muscles except SS and AD). There is a large amount of variation within and among
      muscles for tenderness traits and tenderness-related biochemical traits. These
      results increase our understanding of the sources of variation in tenderness in
      different muscles and provide a basis for the development of muscle-specific
      strategies for improving the quality and value of muscles.

PMID- 14974554
TI  - Rapid chilling cannot prevent inferior pork quality caused by high preslaughter
      stress.
AB  - The present experiment investigated whether increasing chilling rate could
      improve meat quality in pigs exposed to either minimal or high stress immediately
      preslaughter. Pigs (n = 192) were offspring of halothane-free lines. On various
      days, four groups of 48 pigs were processed at a commercial plant. Within each
      group, half the pigs were exposed to either minimal or high preslaughter stress.
      Before entering the cooler at 45 min postmortem, carcasses of both minimal and
      high preslaughter stress treatments were allocated randomly to either
      conventional (+4 degrees C for 22 h) or rapid (three-phase chilling tunnel: -15, 
      10, and -1 degrees C for 15, 38, and 38 min, respectively, followed by storage at
      4 degrees C until 22 h postmortem) chilling. Temperature and pH were measured in
      the blood at exsanguination and in the longissimus lumborum (LL) and
      semimembranosus (SM) muscle at 0.5, 2.5, 4.5, 6.5, and 22 h postmortem. Meat
      quality attributes (water-holding capacity and objective color measurements) were
      assessed on the LL. Preslaughter stress level affected pH and temperature in both
      blood and muscle, with lower (P < 0.001) pH values and higher (P < 0.001)
      temperatures for pigs exposed to high vs. minimal stress. Rapid chilling led to a
      faster (P < 0.001) temperature decline regardless of preslaughter stress level.
      Rapid chilling did not (P > 0.05) influence the rate of pH decline in the LL
      muscle, but reduced (P = 0.061) pH decline in the SM. Rapid chilling, as opposed
      to conventional chilling, decreased (P < 0.05) electrical conductivity in the LL,
      regardless of preslaughter stress; however, it could not compensate for the
      detrimental effect (P < 0.05) of stress on drip loss, filter paper moisture
      absorption, and meat color (L* value). Results from the present study indicated
      that increasing chilling rate is not a suitable method to resolve pork quality
      problems caused by inadequate preslaughter handling.

PMID- 14974555
TI  - The accuracy and repeatability of untrained laboratory consumer panelists in
      detecting differences in beef longissimus tenderness.
AB  - The objective of this study was to determine the accuracy and repeatability of
      untrained laboratory consumer panelists in detecting differences in beef
      longissimus tenderness. At 14 d postmortem, slice shear force was measured on one
      steak from 192 strip loins and used to select 54 strip loins and assign 18 of the
      strip loins to each of three tenderness classes (tender = < 15 kg, intermediate =
      15 to 27 kg, and tough = > 27 kg). Sixty-eight untrained, laboratory consumer
      panelists evaluated paired steaks from each tenderness class in each of two
      sessions (12 total observations per panelist). Mean slice shear forces for
      "tender," "intermediate," and "tough" were 11.1, 21.0, and 32.2 kg, respectively.
      Mean tenderness ratings of the untrained laboratory consumer panel were different
      (P < 0.05) among tenderness classes (mean of 16 panelists = 6.2, 4.9, and 3.3 for
      tender, intermediate, and tough, respectively), and these differences were
      similar regardless of how many untrained panelists were averaged to determine the
      panel mean (4, 8, 12, or 16). The correlations (P < 0.01) between slice shear
      force and the mean untrained consumer panel tenderness rating (mean of 4, r = 
      0.82; mean of 8, r = -0.89; mean of 12, r = -0.91; and mean of 16, r = -0.92;)
      were similar. Overall repeatability of the untrained consumer panel was 0.80.
      Repeatability of individual untrained consumer panelists for tenderness rating
      was highly variable: 31% were > 0.80, 36% were 0.60 to 0.79, and 33% were < 0.60.
      Thirty-two percent of the consumers were both accurate (correlation to slice
      shear force = -0.75 to -1.00, P < 0.01) and repeatable (repeatability > 0.75).
      There is wide variability in the ability of untrained laboratory consumer
      panelists to detect differences in beef tenderness. Nonetheless, untrained
      consumer panels can accurately and repeatedly detect differences in beef
      tenderness under controlled laboratory conditions. An untrained laboratory
      consumer panel may be able to provide as effective an evaluation of beef
      longissimus tenderness as a trained descriptive attribute panel.

PMID- 14974556
TI  - Coping capacity of dairy cows during the change from conventional to automatic
      milking.
AB  - In conventional milking systems, dairy cows are driven to the milking stall twice
      or thrice daily, whereas in automatic milking systems (AMS), the cows enter the
      milking stall voluntarily. In this study, noninvasive methods were used to
      analyze the physiological reaction of 17 cows toward the changeover from
      conventional to automatic milking. Milk yield and composition were analyzed.
      Heart rate was recorded continuously, and feces was sampled twice daily to
      determine cortisol metabolites (11, 17-dioxoandrostanes) for a period of 2 wk.
      During the first visit to the AMS (without milking), heart rate was elevated
      compared with parlor milking by 35 +/- 3 beats per minute (bpm) above basal heart
      rate (P < 0.05). Heart rate during the first milking in AMS (eighth visit) was
      already similar to the heart rate previously measured during milking in the
      parlor (18.1 +/- 2.2 bpm above basal level). Concentration of fecal cortisol
      metabolites was unchanged during the change-over compared with parlor milking. A
      decreased (P < 0.05) milk yield of 68 +/- 7% relative to previous parlor yield
      during the first AMS milking indicated a disturbance of milk ejection in most
      cows. Individual yields ranged from 8 to 96% of the previous parlor yield. To
      examine the relationship between adrenal cortex sensitivity and the coping
      process, an ACTH challenge experiment was performed after the changeover period.
      Cows that released more cortisol after ACTH injection, indicating a higher
      adrenal cortex sensitivity, had a less enhanced heart rate and a near normal milk
      ejection during the first AMS milkings (P < 0.05). In conclusion, the reactions
      toward the changeover to AMS milking varied widely within cows. Adaption to the
      AMS was easier in animals with a higher adrenal cortex sensitivity to ACTH.

PMID- 14974557
TI  - Performance of growing-finishing pigs fed diets containing Roundup Ready corn
      (event nk603), a nontransgenic genetically similar corn, or conventional corn
      lines.
AB  - Two studies were conducted at two locations to evaluate growth performance and
      carcass characteristics of growing-finishing pigs fed diets containing either
      glyphosate-tolerant Roundup Ready (event nk603) corn, a nontransgenic genetically
      similar control corn (RX670), or two conventional sources of nontransgenic corn
      (RX740 and DK647). A randomized complete block design (three and four blocks in
      Studies 1 and 2, respectively) with a 2 x 4 factorial arrangement of treatments
      (two genders and four corn lines) was used. Study 1 used 72 barrows and 72 gilts
      (housed in single-gender groups of six; six pens per dietary treatment) with
      initial and final BW of approximately 22 and 116 kg, respectively. Study 2 used
      80 barrows and 80 gilts (housed in single-gender groups of five; eight pens per
      dietary treatment) with initial and final BW of approximately 30 and 120 kg,
      respectively. Pigs were housed in a modified open-front building in Study 1 and
      in an environmentally controlled finishing building in Study 2. The test corns
      were included at a fixed proportion of the diet in both studies. Animals had ad
      libitum access to feed and water. Pigs were slaughtered using standard procedures
      and carcass measurements were taken. In Study 1, overall ADG, ADFI (as-fed
      basis), and gain:feed (G:F) were not affected (P > 0.05) by corn line. In Study
      2, there was no effect of corn line on overall ADFI (as-fed basis) or G:F ratio.
      In addition, overall ADG of barrows fed the four corn lines did not differ (P >
      0.05); however, overall ADG of gilts fed corn DK647 was greater (P < 0.05) than
      that of pigs fed the other corn lines. There was no effect (P > 0.05) of corn
      line on carcass yield or fatness measurements in either study. Differences
      between barrows and gilts for growth and carcass traits were generally similar
      for both studies and in line with previous research. Overall, these results
      indicate that Roundup Ready corn (nk603) gives equivalent animal performance to
      conventional corn for growing pigs.

PMID- 14974558
TI  - Effect of phosphorylated mannans and pharmacological additions of zinc oxide on
      growth and immunocompetence of weanling pigs.
AB  - Three experiments were conducted to evaluate the efficacy of phosphorylated
      mannans (MAN) and pharmacological levels of ZnO on performance and immunity when
      added to nursery pig diets. Pigs (216 in each experiment), averaging 19 d of age
      and 6.2, 4.6, and 5.6 kg of BW in Exp. 1, 2, and 3, respectively, were blocked by
      BW in each experiment, and penned in groups of six. A lymphocyte blastogenesis
      assay was performed in each experiment to measure in vitro lymphocyte
      proliferation response. In Exp. 1, diets were arranged as a 2 x 2 factorial with
      two levels of Zn (200 and 2,500 ppm) and two levels of MAN (0 and 0.3% from d 0
      to 10, and 0 and 0.2% from d 10 to 38). Zinc oxide increased (P < 0.05) ADG,
      ADFI, and G:F from d 0 to 10, and ADG and ADFI from d 10 to 24. In Exp. 2, diets
      were arranged as a 2 x 3 factorial with two levels of Zn (200 and 2,500 ppm) and
      three levels of MAN (0, 0.2, and 0.3%). Pigs fed 2,500 ppm Zn from d 0 to 10 had
      greater (P < 0.05) ADG, ADFI, and G:F than pigs fed 200 ppm Zn. From d 10 to 24,
      ADG was similar when pigs were fed 200 ppm Zn, regardless of MAN supplementation;
      however, ADG increased (P < 0.05) when 0.2% MAN was added to dietscontaining
      2,500 ppm Zn (MAN x Zn interaction, P < 0.05). In Exp. 3, diets were arranged as
      a 2 x 3 factorial with two levels of MAN (0 and 0.3%) and three levels of Zn
      (200, 500, and 2,500 ppm). Zinc was maintained at 200 ppm from d 21 to 35, so
      only two dietary treatments (0 and 0.3% MAN) were fed during this period. Average
      daily gain was greater (P < 0.05) from d 7 to 21 when pigs were fed 2,500 ppm Zn
      compared with pigs fed 200 or 500 ppm Zn. The addition of MAN improved (P < 0.05)
      G:F from d 7 to 21 and d 0 to 35. Lymphocyte proliferation of unstimulated cells
      and phytohemagglutinin-stimulated cells was decreased (P < 0.05) in cells
      isolated from pigs fed MAN compared with cells isolated from pigs fed diets
      without MAN. Lymphocyte proliferation of pokeweed mitogen-stimulated cells
      isolated from pigs fed MAN was less (P < 0.05) than for pigs fed diets devoid of
      MAN when diets contained 200 ppm Zn; however, MAN had no effect on lymphocyte
      proliferation when the diet contained 500 or 2,500 ppm Zn (MAN x Zn interaction,
      P < 0.05). Although the magnitude of response to MAN was not equivalent to that
      of pharmacological concentrations of Zn, MAN mayimprove growth response when
      pharmacological Zn levels are restricted.

PMID- 14974559
TI  - Antioxidant supplementation and subsequent oxidative stress of horses during an
      80-km endurance race.
AB  - This study tested the development of oxidative stress and the effects of
      antioxidant supplementation in an 80-km ride. A precompetition survey revealed
      that no competitor would participate without vitamin E supplementation;
      therefore, 46 horses were paired for past performances and randomly assigned to
      two groups of 23 each for 3 wk of supplementation before the ride. One group (E)
      was orally supplemented with 5,000 IU of vitamin E per day; the other group (E+C)
      received that dose of vitamin E plus 7 g/d of vitamin C. Blood samples,
      temperature, and heart rate were taken the day before the race, at 21 and 56 km
      during the ride, at completion, and after 20 min of recovery. Plasma was assayed
      for lipid hydroperoxides, alpha-tocopherol, total ascorbate, albumin, creatine
      kinase (CK), and aspartate aminotransferase (AST). Total glutathione and
      glutathione peroxidase activity were determined in red blood cells and white
      blood cells. Thirty-four horses completed the race, 12 horses (six in E and six
      in E+C) did not finish for reasons including lameness, metabolic problems, and
      rider option. Plasma ascorbate was higher (P = 0.045) in the E+C group than in
      the E group. Other than ascorbate, neither antioxidant status nor CK and AST
      activities were affected by supplementation with E+C vs. E. Red blood cell
      glutathione peroxidase, white blood cell total glutathione, lipid hydroperoxides,
      CK, and AST increased, and red blood cell total glutathione and white blood cell
      glutathione peroxidase activity decreased with distance (P < 0.001). Positive
      correlations were found for plasma lipid hydroperoxides on CK (r = 0.25; P =
      0.001) and AST (r = 0.33; P < 0.001). These results establish an association
      between muscle leakage and a cumulative index of oxidative stress.

PMID- 14974560
TI  - Performance of hair sheep composite breeds: resistance of lambs to Haemonchus
      contortus.
AB  - This study was designed to evaluate breed differences in resistance to Haemonchus
      contortus in lambs. A total of 181 ewe lambs representing crossbred Dorsets (DO)
      and Dorpers (DP; out of 1/2-Dorset, 1/4-Rambouillet, 1/4-Finnsheep ewes) and
      straight-bred Katahdins (KT) were evaluated over 3 yr. An additional 144 DO, DP,
      KT, and Barbados Blackbelly x St. Croix (HH) wethers were evaluated over 2 yr.
      Lambs were weaned at 60 to 90 d of age. After deworming at about 4 mo of age, ewe
      lambs received approximately 10,000 infective larvae and were evaluated for
      parasite resistance in drylot, whereas wethers were evaluated on pasture under
      conditions of natural infection. Each sex was analyzed separately. Egg counts per
      gram of feces (FEC), log-transformed FEC (LFEC), packed cell volumes (%), and
      body weights (kg) measured at 3, 4, 5, and 6 wk after deworming and reinfection
      were analyzed. Breed influenced all traits (P < 0.05) except BW in ewe lambs and
      PCV in wethers. Year and week influenced (P < 0.05) all traits. At most times, DP
      had the highest FEC, DO had the lowest PCV, and KT and HH had lower FEC and
      higher PCV than either DO or DP. Clearly, Dorper sheep were not more resistant to
      parasites than DO, but they were able to cope with infection better by
      maintaining similar or higher (P < 0.05) PCV and similar BW. Katahdin and HH were
      more resistant, with lower FEC (P < 0.05) than DO or DP. Breed differences were
      more apparent when infection levels were higher; DO and DP were less affected
      when infection levels were low and when animals were on a better plane of
      nutrition. Caribbean hair sheep originated in hot, humid regions of West Africa.
      They and the derivative Katahdin breed seem relatively resistant to parasitism.
      The Dorper, in contrast, was developed in more arid regions and exhibited little
      parasite resistance.

PMID- 14974561
TI  - Effect of aluminum chloride and dietary phytase on relative ammonia losses from
      swine manure.
AB  - Ammonia (NH3) losses from swine manure contribute to odor problems, decrease
      animal productivity, and increase the risk of acid rain deposition. This study
      was conducted to determine whether aluminum chloride (AlCl3) or dietary
      manipulation with phytase could decrease relative NH3 losses from swine manure.
      Twenty-four pens of nursery pigs were used in two trials, and the pigs were fed
      normal or phytase-supplemented (500 IU/kg) diets. Aluminum chloride was added to
      manure pits (1.9 x 1.2 x 0.5 m) under each pen at 0, 0.25, 0.50, or 0.75%
      (vol:vol) of final manure volume. Manure pH and NH3 losses (measured by relative
      NH3 flux) were determined twice weekly. The addition of AlCl3 at 0.75% decreased
      (P < 0.05) manure pH from 7.48 to 6.69. Phytase decreased (P < 0.05) manure pH to
      7.07 compared with 7.12 in the normal diet manure. Aluminum chloride administered
      at 0.75% without phytase reduced (P < 0.05) relative NH3 losses 52% for the
      entire 6-wk period. Relative NH3 losses were decreased (P < 0.05) from 109 mg of
      NH3/(m2 x h) in pens containing pigs fed the normal diet without AlCl3 to 81 mg
      of NH3/(m2 x h) in pens housing pigs administered the phytase diet, a 26%
      reduction. When the phytase diet and 0.75% AlCl3 additions were used in
      combination, relative NH3 losses were reduced (P < 0.05) by 60% compared with
      pens of pigs fed the control diet without AlCl3. Decreases in manure pH were
      likely responsible for the observed reduction in NH3 losses. Multiple regression
      was performed with relative rates of NH3 losses as the dependent variable and
      rate of AlCl3 addition, diet, and manure pH as independent variables. The model
      was tested using a stepwise regression (P < 0.001), and results indicated that
      the most important factors determining NH3 losses were manure pH and diet.
      However, the contribution of AlCl3 cannot be discounted. When manure pH was
      regressed against AlCl3 and dietary phytase, AlCl3 levels accounted for 64% of
      the variation in manure pH (P < 0.001). Dietary manipulation with phytase and
      application of AlCl3 to manure are promising management practices for the
      reduction of NH3 from swine facilities.

PMID- 14974562
TI  - Relationship between litter birth weight and litter size in six breeds of sheep.
AB  - Metabolizable energy requirements of the ewe increase during pregnancy due to
      increases in fetal and maternal metabolism. Fetal metabolism is related to total
      weight of the fetuses. Fetal number is a primary contributor to fetal weight.
      Litter birth weight represents the culminated fetal growth of the litter and can
      be used to estimate the effect of fetal metabolism on energy requirements of the
      ewe. We hypothesized that litter weight in sheep would increase at a decreasing
      rate with increasing litter size. Birth weights of lambs born to yearling (11 to
      15 mo) and mature ewes (> 34 mo) were collected on litters born to Dorset,
      Rambouillet, Suffolk, Finnsheep, Romanov, and Composite III ewes mated to produce
      straightbred lambs. Litter birth weight expressed as a function of litter size
      increased at a decreasing rate and the quadratic term differed from zero for
      mature Rambouillet, Suffolk, Finnsheep, Romanov, and Composite III litters (P <
      0.042). The quadratic coefficient differed among breeds. In yearlings, litter
      weight increased at a decreasing rate for Suffolk ewes (P = 0.002). The quadratic
      term for the relationship between litter weight and litter size did not differ
      from zero for Finnsheep (P = 0.39) or Romanov litters (P = 0.07). The hypothesis
      that litter weight increases at a decreasing rate with increased litter size is
      supported by experimental results.

PMID- 14974563
TI  - Effects of ribose supplementation on selected metabolic measurements and
      performance in maximally exercising Thoroughbreds.
AB  - The objective of this study was to investigate the effects of ribose
      supplementation on blood ammonia-N, plasma lactic acid, plasma glucose, volume of
      oxygen consumption (VO2), heart rate, and performance in Thoroughbred geldings
      performing a maximal treadmill standardized exercise test (SET). The hypothesis
      tested was that ribose supplementation would decrease ammonia-N and lactic acid
      accumulation during exercise, and improve performance. Eight Thoroughbred
      geldings were assigned randomly to one of two groups: glucose or ribose. The
      glucose group received 0.15 g glucose/kg of BW, and the ribose group received
      0.15 g of ribose/kg BW top-dressed on the feed twice daily. After 2 wk of glucose
      or ribose supplementation, a SET was performed. Blood was analyzed for blood
      ammonia-N, plasma lactic acid, and plasma glucose before exercise (0 min), every
      minute during SET, and at 15 and 30 min after exercise. Heart rate and VO2 were
      recorded for the duration of SET. After a 10-d washout period, geldings switched
      groups. Following another 2 wk of supplementation, a second SET was performed,
      and same data recorded. Blood ammonia-N and plasma lactic acid increased as
      duration of SET increased and reached a peak at 15 min after exercise. Peak
      plasma glucose was observed at 15 min after exercise, and peak heart rate and VO2
      were recorded at highest speed during SET. Geldings supplemented with ribose had
      blood ammonia-N, plasma lactic acid, plasma glucose, VO2, heart rate, and
      performance similar to those of geldings supplemented with glucose. Results from
      this study show that supplementation with 0.15 g ribose/kg BW twice daily in the
      diet of conditioned Thoroughbred geldings for 2 wk does not influence blood
      ammonia-N, plasma lactic acid, plasma glucose, VO2, heart rate, or performance
      during SET or the first 30 min of recovery.

PMID- 14974564
TI  - Effect of vitamin supplements on some aspects of performance, vitamin status, and
      semen quality in boars.
AB  - The aim of the present study was to determine the effects of dietary supplements
      of vitamins on vitamin status, libido, and semen characteristics in young boars
      under normal and intensive semen collection. Sixty Landrace, Yorkshire, and Duroc
      boars were allocated randomly from 6 to 10 mo of age to one of the following
      diets: 1) basal diet (industry level) for minerals and vitamins (Control, n =
      15); 2) basal diet supplemented with vitamin C (ASC, n = 15); 3) basal diet
      supplemented with fat-soluble vitamins (FSV, n = 15); and 4) basal diet
      supplemented with water-soluble vitamins (WSV, n = 15). After puberty
      (approximately 12 mo of age), semen was collected at a regular frequency (three
      times every 2 wk) for 5 wk. Thereafter, all boars were intensively collected
      (daily during 2 wk). A recovery period (semen collection three times every 2 wk)
      followed and lasted for 10 wk. Sperm quality (percentage of motile cells and
      percentage of morphologically normal cells) and quantity (sperm concentration,
      semen volume, and total sperm number) were recorded as well as direct and hormone
      related measurements of boar libido. Blood and seminal plasma samples were taken
      to monitor vitamin status. High concentrations of B6 (P < 0.05) and folic acid (P
      < 0.05) were observed in the blood plasma of WSV boars, whereas greater
      concentrations of vitamin E (P < 0.01) were obtained in FSV boars. In the seminal
      plasma, folic acid concentrations tended to be greater in WSV boars (P < 0.08).
      During the intensive collection period, there was a tendency (P < 0.06) for semen
      production to be greater in WSV boars, the effect being less pronounced (P <
      0.10) in FSV boars. During the recovery period, the percentage of motile sperm
      cells was greater in WSV boars (P < 0.03) and, to a lesser extent, in FSV boars
      (P < 0.10) compared with Control boars. Sperm morphology and libido were not
      affected by treatments. These results indicate that the transfer of vitamins from
      blood to seminal plasma is limited and the dietary supplements of water-soluble
      and fat-soluble vitamins may increase semen production during intensive semen
      collection.

PMID- 14974565
TI  - Effects of endophyte-infected tall fescue on indicators of thermal status and
      growth in Hereford and Senepol steers.
AB  - Poor growth often occurs in cattle consuming ergot alkaloids associated with
      endophyte-infected (EI) tall fescue. Hyperthermia may contribute significantly to
      poor growth resulting from fescue toxicosis. This study examined indicators of
      thermal status and growth in Hereford (n = 30; heat-sensitive Bos taurus; H) and
      Senepol (n = 28; heat-tolerant Bos taurus; S) steers fed EI tall fescue (TF) or
      orchardgrass (OG) in 2 x 2 factorial experiments. Respiration rates, daytime
      shade use, tail skin temperatures, and body weights were measured during the
      summer and fall of 2000 (Exp. 1) and 2001 (Exp. 2). Experimental diets consisted
      of hay and seed for 12 wk in 2000, hay for 6 wk during the summer of 2001, and
      hay plus seed for 6 wk during the fall of 2001. In Exp. 1, EI tall fescue
      increased (P < 0.01) respiration rates, shade use, and skin temperatures in both
      breeds. Breed x diet affected (P < 0.01) 12-wk ADG in Exp. 1. Growth rate was
      lower for H-TF (262 g/d) than for S-TF, S-OG, and H-OG (475, 497, and 524 g/d,
      respectively). In Exp. 2, Senepol had lower (P < 0.01) respiration rates, shade
      use, and skin temperatures compared with Hereford, but diet did not alter (P >
      0.14) these indicator traits in either breed. Breed x diet affected (P < 0.01)
      summer growth rates. Growth rate was lower for H-TF (88 g/d) than for H-OG, S-TF,
      and S-OG (508, 555, and 566 g/d, respectively). Adding seed to the diets in Exp.
      2 decreased (P < 0.01) ADG for both breeds on TF during the fall. Thermal status
      indicator traits in Senepol and Hereford steers were similarly altered by TF;
      however, only Hereford showed consistently poor growth. Senepol showed resilience
      in their capacity for growth under conditions of fescue toxicosis. Senepol
      influence may enhance cattle performance in production systems that use EI tall
      fescue as the base forage.

PMID- 14974566
TI  - Questions conclusions in article on dorsolateral subluxation method.

PMID- 14974567
TI  - Effects of bovine lactoferrin hydrolysate on the in vitro antimicrobial
      susceptibility of Escherichia coli strains isolated from baby pigs.
AB  - OBJECTIVE: To determine the antibacterial activity of bovine lactoferrin
      hydrolysate (bLf-lysate) alone or in combination with other antimicrobials
      against antimicrobial-resistant Escherichia coli strains isolated from baby pigs.
      SAMPLE POPULATION: 3 clinical strains of E coli were isolated from baby pigs with
      severe diarrhea and designated as strains 9061, 9062, and 9065. PROCEDURE: The
      broth microdilution checkerboard and fractional inhibitory (or bactericidal)
      concentration index were used to evaluate the antibacterial effect elicited by
      bLf-lysate in combination with kanamycin, gentamicin, cephalothin, cefamandole,
      penicillin G, ampicillin, tetracycline, erythromycin, or rifampicin against the 3
      strains of E coli. RESULTS: The 3 strains of E coli were susceptible to
      gentamicin and rifampicin but highly resistant to most of the other
      antimicrobials tested, except for strain 9061 that was also susceptible to
      cephalothin but intermediately inhibited by kanamycin and cefamandole.
      Synergistic growth-inhibitory activity was observed between bLf-lysate and
      gentamicin against 1 strain of E coli (strain 9062); synergistic bactericidal
      activity was found between bLf-lysate and rifampicin against all 3 strains of E
      coli. Moreover, partial synergy was observed between bLf-lysate and kanamycin,
      gentamicin, cephalothin, or cefamandole against the strains of E coli, but this
      partial synergistic activity was mostly seen against only 1 of the strains.
      Little interaction between bLf-lysate and tetracycline, ampicillin, penicillin G,
      or erythromycin was observed against the clinical strains of E coli. CONCLUSIONS
      AND CLINICAL RELEVANCE: A combination of bLf-lysate and certain antimicrobials
      may prove clinically effective against antimicrobial-resistant strains of E coli.

PMID- 14974568
TI  - Evaluation of effects of dietary carbohydrate on formation of struvite crystals
      in urine and macromineral balance in clinically normal cats.
AB  - OBJECTIVE: To evaluate effects of dietary carbohydrate on urine volume; struvite
      crystal formation; and calcium, phosphorus, and magnesium balance in clinically
      normal cats. ANIMALS: 21 healthy adult cats (15 sexually intact males and 6
      sexually intact females). PROCEDURE: Diets containing no carbohydrate source
      (control diet), control plus starch, or control plus fiber were given in a 3 X 3
      Latin-square design. The diets were available ad libitum in study 1 (n = 12) and
      given under restrictions in study 2 (9) to equalize daily intakes of crude
      protein among the 3 groups. Formation of struvite crystals and balance of
      calcium, phosphorus, and magnesium were measured. RESULTS: Urine volume was lower
      in the starch group and fiber group in study 1, whereas no differences were
      detected among the groups in study 2. Urinary pH and struvite activity product
      were higher in the starch group in both studies, and the fiber group also had
      higher struvite activity product in study 2. In both studies, urinary
      concentrations of HCl-insoluble sediment were higher in the starch group and
      fiber group. In the fiber group, a net loss of body calcium, phosphorus, and
      magnesium was detected in study 2. CONCLUSIONS AND CLINICAL RELEVANCE: Starch and
      fiber in diets potentially stimulate formation of struvite crystals. Hence,
      reducing dietary carbohydrate is desirable to prevent struvite urolith formation.
      In addition, a net loss of body calcium, phosphorus, and magnesium during feeding
      of the fiber diet suggests that dietary inclusion of insoluble fiber could
      increase macromineral requirements of cats.

PMID- 14974569
TI  - Evaluation of serum concentrations of biomarkers of skeletal metabolism and
      results of radiography as indicators of severity of osteochondrosis in foals.
AB  - OBJECTIVE: To determine whether serum concentrations of biomarkers of skeletal
      metabolism can, in conjunction with radiographic evaluation, indicate severity of
      osteochondrosis in developing horses. ANIMALS: 43 Dutch Warmblood foals with
      varying severity of osteochondrosis. PROCEDURE: 24 foals were monitored for 5
      months and 19 foals were monitored for 11 months. Monthly radiographs of
      femoropatellar-femorotibial and tibio-tarsal joints were graded for osteochondral
      abnormalities. Serial blood samples were assayed for 8 cartilage and bone
      biomarkers. At the end of the monitoring period, foals were examined for
      macroscopic osteochondrosis lesions. RESULTS: Temporal relationships were evident
      between certain serum biomarkers and osteochondrosis severity in foals during
      their first year. Biomarkers of collagen degradation (collagenase-generated
      neoepitopes of type-II collagen fragments, type-I and -II collagen fragments
      [COL2-3/4C(short)], and cross-linked telopeptide fragments of type-I collagen)
      and bone mineralization (osteocalcin) were positive indicators of osteochondrosis
      severity at 5 months of age. In foals with lesions at 11 months of age,
      osteochondrosis severity correlated negatively with COL2-3/4C(short) and
      osteocalcin and positively with C-propeptide of type-II procollagen (CPII), a
      collagen synthesis marker. Radiographic grading of osteochondrosis lesions
      significantly correlated with macroscopic osteochondrosis severity score at both
      ages and was strongest when combined with osteocalcin at 5 months and CPII at 11
      months. CONCLUSIONS AND CLINICAL RELEVANCE: The ability of serum biomarkers to
      indicate osteochondrosis severity appears to depend on stage of disease and is
      strengthened with radiography. In older foals with more permanent lesions,
      osteochondrosis severity is significantly related to biomarker concentrations of
      decreased bone formation and increased cartilage synthesis.

PMID- 14974570
TI  - Evaluation of the bioequivalence of two formulations of deltamethrin for
      treatment of sheep with psoroptic mange.
AB  - OBJECTIVE: To evaluate efficacy of 2 deltamethrin emulsifiable concentrates that
      differed on the basis of vehicle (methyl glycol acetate [AMG] or 2-propylene
      glycol 1-methyl ether acetate [AMP]) for the treatment of sheep with mange.
      ANIMALS: 30 ewes between 11 months and 7 years old that weighed 16 to 71 kg and
      were naturally infested with Psoroptes ovis. PROCEDURE: Sheep were randomly
      allocated into 3 groups (13 sheep in group AMP, 13 sheep in group AMG, and 4
      negative-control sheep). Each sheep was dipped twice (10-day interval between
      dippings) in the assigned formulation. Assessment of efficacy was performed on
      days 3, 7, 14, 21, 28, 35, 42, 49, 56, and 63 after the first dipping. Efficacy
      was assessed by determining the number of eggs or live mites on those days, as
      well as regrowth of wool at the end of the study. RESULTS: Psoroptic mange
      infestation was maintained in the 4 control sheep throughout the study. We did
      not detect live Psoroptes mites in scrapings after day 7 (AMP group) or after day
      14 (AMG group). No parasites were seen after day 14 in either treatment group.
      Therefore, efficacy was 100% for both treatment groups from days 14 to 63.
      CONCLUSIONS AND CLINICAL RELEVANCE: The 2 formulations of deltamethrin were
      equally able to eradicate Psoroptes infestation of sheep after 2 dippings
      performed in accordance with the label recommendations.

PMID- 14974571
TI  - Electromyographic activity of the longissimus dorsi muscles in horses during
      trotting on a treadmill.
AB  - OBJECTIVE: To use electromyography (EMG) to measure physiologic activity of the
      longissimus dorsi muscles of horses during trotting on a treadmill. ANIMALS: 15
      adult horses (5 to 20 years old that weighed 450 to 700 kg) that did not have
      clinical signs of back pain. PROCEDURE: Data were recorded for each horse during
      trotting on a treadmill at speeds of 2.6 to 4.4 m/s. Surface electromyography was
      recorded bilaterally from the longissimus dorsi muscles at the levels of T12,
      T16, and L3. RESULTS: In each motion cycle, 2 EMG maxima were found at the end of
      the diagonal stance phases. The EMG activity peaked slightly later at L3 than at
      T12 and T16. Maximum EMG amplitudes were highest at T12 and decreased caudally,
      with mean +/- SD values of 4.51 +/- 1.20 mV at T12, 3.00 +/- 0.83 mV at T16, and
      1.78 +/- 0.67 mV at L3. Mean minimum EMG activity was 1.30 +/- 0.63 mV at T12,
      0.83 +/- 0.35 mV at T16, and 0.80 +/- 0.39 mV at L3. The relative amplitudes (ie,
      [maximum - minimum]/maximum) were 67 +/- 11% at T12, 66 +/- 8% at T16, and 71 +/-
      8% at L3. CONCLUSIONS AND CLINICAL RELEVANCE: Activity of the longissimus dorsi
      muscles is mainly responsible for stabilization of the vertebral column against
      dynamic forces. The difference between minimum and maximum activity may allow
      application of this method as a clinical tool. Data reported here can serve as
      reference values for comparison with values from clinically affected horses.

PMID- 14974572
TI  - Kinetic analysis of demethylation of 13C-aminopyrine in healthy dogs.
AB  - OBJECTIVE: To describe the kinetics of demethylation of 13C-aminopyrine in
      healthy dogs for use in determining the most appropriate time for collection of
      blood samples for a 13C-aminopyrine demethylation blood test for evaluation of
      hepatic function. ANIMALS: 9 healthy dogs. PROCEDURES: A 2-mL baseline blood
      sample was collected into an evacuated heparinized tube, and 13C-aminopyrine was
      administered to each dog (2 mg/kg, IV). Additional 2-mL blood samples were
      collected 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 180, 240, 300, and 360
      minutes after 13C-aminopyrine administration. The CO2 was extracted from blood
      samples by addition of a strong acid, and the percentage dose of 13CO2 (PCD) in
      the extracted gas was determined by fractional mass spectrometry. RESULTS: No
      dogs had gross evidence of adverse effects, and all had an increase in PCD after
      IV administration of 13C-aminopyrine. The PCD had the least variability among 5
      variables used to evaluate hepatic demethylating capacity. Peak PCD was detected
      at 30 minutes in 1 dog, 45 minutes in 5 dogs, 60 minutes in 2 dogs, and 75
      minutes in 1 dog. The mean PCD for the 9 dogs peaked at 45 minutes after 13C
      aminopyrine administration. CONCLUSIONS AND CLINICAL RELEVANCE: PCD appears to be
      the preferable variable for evaluation of hepatic demethylating capacity.
      Intravenous administration of 13C-aminopyrine leads to a consistent increase in
      PCD. Mean PCD peaked 45 minutes after administration, suggesting that blood
      sample collection 45 minutes after 13C-aminopyrine administration may be
      appropriate for use in estimating hepatic demethylating capacity.

PMID- 14974573
TI  - Characterization of gelatinases in bronchoalveolar lavage fluid and gelatinases
      produced by alveolar macrophages isolated from healthy calves.
AB  - OBJECTIVE: To characterize gelatinases in bronchoalveolar lavage fluid (BALF) and
      gelatinases produced by alveolar macrophages of healthy calves. SAMPLE
      POPULATION: Samples of BALF and alveolar macrophages obtained from 20 healthy 2
      month-old calves. PROCEDURE: BALF was examined by use of gelatin zymography and
      immunoblotting to detect gelatinases and tissue inhibitor of metalloproteinase
      (TIMP)-1 and -2. Cultured alveolar macrophages were stimulated with
      lipopolysaccharide (LPS), and conditioned medium was subjected to zymography.
      Alveolar macrophage RNA was used for reverse transcriptase-polymerase chain
      reaction assay of matrix metalloproteinases (MMPs), cyclooxygenase-2, and
      inducible nitric oxide synthase. RESULTS: Gelatinolytic activity in BALF was
      evident at 92 kd (14/20 calves; latent MMP-9) and 72 kd (18/20; latent MMP-2).
      Gelatinolytic activity was evident at 82 kd (10/20 calves; active MMP-9) and 62
      kd (17/20; active MMP-2). Gelatinases were inhibited by metal chelators but not
      serine protease inhibitors. Immunoblotting of BALF protein and conditioned medium
      confirmed the MMP-2 and -9 proteins. Endogenous inhibitors (ie, TIMPs) were
      detected in BALF from all calves (TIMP-1) or BALF from only 4 calves (TIMP-2).
      Cultured alveolar macrophages expressed detectable amounts of MMP-9 mRNA but not
      MMP-2 mRNA. CONCLUSIONS AND CLINICAL RELEVANCE: Healthy calves have detectable
      amounts of the gelatinases MMP-2 and -9 in BALF Endogenous inhibitors of MMPs
      were detected in BALF (ie, TIMP-1, all calves; TIMP-2, 4 calves).
      Lipopolysaccharide-stimulated alveolar macrophages express MMP-9 but not MMP-2
      mRNA. The role of proteases in the pathogenesis of lung injury associated with
      pneumonia has yet to be determined.

PMID- 14974574
TI  - Concentrations of gentamicin in serum and bronchial lavage fluid after once-daily
      aerosol administration to horses for seven days.
AB  - OBJECTIVE: To assess gentamicin concentrations in serum and bronchial lavage
      fluid (BLF) of horses during a 24-hour period after once-daily aerosol
      administration of gentamicin (GAER) for 7 days and the pattern and degree of
      bronchial tree inflammation associated with repeated GAER. ANIMALS: 13 healthy
      adult horses (9 geldings and 4 mares). PROCEDURE: The treatment group comprised 8
      horses, and 5 horses were untreated control animals. Gentamicin (20 mL of
      gentamicin [50 mg/mL]) was administered via aerosol once daily for 7 days.
      Samples of serum and BLF were obtained from all horses before GAER and 0.5, 4, 8,
      and 24 hours after the final day of GAER. Gentamicin concentrations were
      determined for all samples from treated horses, and cytologic examinations were
      performed on all BLF samples. RESULTS: Peak median BLF gentamicin concentration
      detected at 0.5 hours was 2.50 microg/mL. Median serum gentamicin concentration
      was < 0.50 microg/mL at all time points. Significant differences were not
      observed in total nucleated cell counts or differential cell counts in BLF
      between groups at any time point. Neutrophil count in BLF for all horses was
      increased over baseline at 4 and 24 hours. CONCLUSIONS AND CLINICAL RELEVANCE: We
      did not detect evidence of gentamicin accumulation or respiratory inflammation
      after once-daily GAER for 7 days. This protocol appears unlikely to result in
      local or systemic toxicosis. Repeated daily GAER to horses appears to be a safe
      procedure and may have clinical use in the treatment of horses with bacterial
      infections of the airways.

PMID- 14974575
TI  - Effects of atracurium on intraocular pressure, eye position, and blood pressure
      in eucapnic and hypocapnic isoflurane-anesthetized dogs.
AB  - OBJECTIVE: To determine effects of atracurium on intraocular pressure (IOP), eye
      position, and arterial blood pressure in eucapnic and hypocapnic dogs
      anesthetized with isoflurane. ANIMALS: 16 dogs. PROCEDURE: Ventilation during
      anesthesia was controlled to maintain Paco2 at 38 to 44 mm Hg in group- I dogs (n
      = 8) and 26 to 32 mm Hg in group-II dogs (8). Baseline measurements for IOP,
      systolic, diastolic, and mean arterial blood pressure, central venous pressure
      (CVP), and heart rate (HR) were recorded. Responses to peroneal nerve stimulation
      were monitored by use of a force-displacement transducer. Atracurium (0.2 mg/kg)
      was administered i.v. and measurements were repeated at 1, 2, 3, and 5 minutes
      and at 5-minute intervals thereafter for 60 minutes. RESULTS: Atracurium did not
      affect IOP, HR, or CVP Group II had higher CVP than group I, but IOP was not
      different. There was no immediate effect of atracurium on arterial blood
      pressure. Arterial blood pressure increased gradually over time in both groups.
      Thirty seconds after administration of atracurium, the eye rotated from a
      ventromedial position to a central position and remained centrally positioned
      until 100% recovery of a train-of-four twitch response. The time to 100% recovery
      was 53.1 +/- 5.3 minutes for group I and 46.3 +/- 9.2 minutes for group II.
      CONCLUSIONS AND CLINICAL RELEVANCE: Atracurium did not affect IOP or arterial
      blood pressure in isoflurane-anesthetized dogs. Hyperventilation did not affect
      IOP or the duration of effect of atracurium.

PMID- 14974576
TI  - Evaluation of an electrolyte analyzer for measurement of ionized calcium and
      magnesium concentrations in blood, plasma, and serum of dogs.
AB  - OBJECTIVE: To evaluate an electrolyte analyzer for measurement of ionized calcium
      (Ca(i)) and magnesium (Mg(i)) concentrations in blood, plasma, and serum;
      investigate the effect of various factors on measured values; and establish
      reference ranges for Ca(i) and Mg(i) in dogs. ANIMALS: 30 healthy adult dogs of
      various breeds. PROCEDURE: Precision in a measurement series, day-to-day
      precision, and linearity were used to evaluate the analyzer. The effects of
      exposure of serum samples to air, type of specimen (blood, plasma, or serum), and
      storage temperature on sample stability were assessed. Reference ranges were
      established with anaerobically handled serum. RESULTS: The coefficient of
      variation for precision in a measurement series was < or = 1.5% for both
      electrolytes at various concentrations. The Ca(i) and Mg(i) concentrations were
      significantly lower in aerobically handled serum samples, compared with
      anaerobically handled samples. The Ca(i) and Mg(i) concentrations differed
      significantly among blood, plasma, and serum samples. In anaerobically handled
      serum, Ca(i) was stable for 24 hours at 22 degrees C, 48 hours at 4 degrees C,
      and 11 weeks at -20 degrees C; Mg(i) was stable for 8 hours at 22 degrees C, < 24
      hours at 4 degrees C, and < 1 week at -20 degrees C. In anaerobically handled
      serum, reference ranges were 1.20 to 1.35 mmol/L for Ca(i) and 0.42 to 0.58
      mmol/L for Mg(i). CONCLUSIONS AND CLINICAL RELEVANCE: The electrolyte analyzer
      was suitable for determination of Ca(i) and Mg(i) concentrations in dogs.
      Accurate results were obtained in anaerobically handled serum samples analyzed
      within 8 hours and kept at 22 degrees C.

PMID- 14974577
TI  - Determination of passive mechanical properties of the superficial and deep
      digital flexor muscle-ligament-tendon complexes in the forelimbs of horses.
AB  - OBJECTIVE: To determine the relative contributions of the muscles, tendons, and
      accessory ligaments to the passive force-length properties of the superficial
      (SDF) and deep digital flexor (DDF) myotendinous complexes. SAMPLE POPULATION: 8
      cadaveric forelimbs from 6 adult Thoroughbreds. PROCEDURE: In vitro, limb
      configurations during slack position and myotendinous lengths during subsequent
      axial loading of forelimbs were recorded before and after transection of
      accessory ligaments. Expressions were derived to describe the force-length
      behavior of each muscle, tendon, and accessory ligament-tendon unit; linear
      stiffness was computed for these components. The elastic modulus was established
      for the SDF and DDF tendons. RESULTS; Linear stiffness was 2.80 +/- 0.38 kN/cm
      for the SDF muscle, 3.47 +/- 0.66 kN/cm for the DDF muscle, 2.73 +/- 0.18 kN/cm
      for the SDF tendon, 3.22 +/- 0.20 kN/cm for the DDF tendon, 6.46 +/- 0.85 kN/cm
      for the SDF accessory ligament, 1.93 +/- 0.11 kN/cm for the SDF accessory
      ligament-tendon unit, and 2.47 +/- 0.11 kN/cm for the DDF accessory ligament
      tendon unit. The elastic modulus for the SDF and DDF tendons was 920 +/- 77 and
      843 +/- 56 MPa, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Both the muscle
      tendon and ligament-tendon portions of SDF and DDF myotendinous complexes had
      important roles in supporting the forelimb of horses. Although muscle tension can
      be enhanced by elbow joint flexion and active contraction, the accessory
      ligaments transmitted more force to the distal tendons than did the muscles under
      the conditions tested.

PMID- 14974578
TI  - Effects of extracorporeal shock wave therapy and radial pressure wave therapy on
      elasticity and microstructure of equine cortical bone.
AB  - OBJECTIVE: To measure changes in the modulus of elasticity (E) and describe
      histologic findings after extracorporeal shock wave therapy and radial pressure
      wave therapy on equine cortical bone specimens. SAMPLE POPULATION: 16 bone
      specimens from the proximodorsal cortex of an equine third metacarpal or
      metatarsal bone. PROCEDURE: Baseline E was determined by the density (p) and
      unidirectional ultrasound transmission velocity (C) of each specimen according to
      the equation E = pC2. Eight specimens were treated with 500 pulses of 0.15 mJ/mm2
      of extracorporeal shock wave therapy, and 8 specimens were treated with 500
      pulses of 0.16 mJ/mm2of radial pressure wave therapy. After treatment, C was
      determined again. Four treatment sessions resulted in 2,000 pulses and 5 C
      measurements. The p of each sample was measured again. Mean post-treatment E was
      calculated for each group. Nondecalcified sections of all specimens were stained
      with toluidine blue or basic fuchsin for histologic evaluation. RESULTS: Overall
      treatment group effect was not significant for C or E. Final E was not different
      from baseline values for extracorporeal shock wave therapy and radial pressure
      wave therapy. No histologic changes could be attributed to either treatment
      modality. CONCLUSIONS AND CLINICAL RELEVANCE: Extracorporeal shock wave therapy
      and radial pressure wave therapy did not affect the material properties of equine
      bone at the energy and pulse values used in this study.

PMID- 14974579
TI  - Isolation, characterization, and expression of feline stromelysin-1 in naturally
      developing tumors in cats.
AB  - OBJECTIVE: To detect, isolate, and characterize feline stromelysin-1 (ie, matrix
      metalloproteinase [MMP]-3) in naturally developing tumors in cats. SAMPLE
      POPULATION: 31 tissue samples obtained from primary tumors and 6 samples of
      normal tissues from cats. PROCEDURE: Biopsy specimens were obtained from primary
      tumors. Primers were designed on the basis of known sequences. The sequence of
      stromelysin-1 was cloned and analyzed. An additional primer set was used as a
      screening tool. Samples were assayed in duplicate or triplicate, when possible.
      Data obtained were analyzed for differences in expression of stromelysin-1 with
      regard to overall survival among cats of various sex, age, and disease status.
      RESULTS: A 1,181-bp cDNA nucleotide sequence was amplified. The open reading
      frame encoded 393 amino acids. This amino acid sequence shared 70% to 85%
      sequence homology with sequences of other species. In addition, samples were
      screened for stromelysin-1. Of the 31 tumor samples tested, 16 (51.6%) had
      positive results for expression of stromelysin-1. Total RNA expression was
      detected in a diverse group of tumor types. Prognostic factors associated with a
      shorter duration of survival included evidence of metastasis and metastasis
      associated with expression of stromelysin-1. CONCLUSIONS AND CLINICAL RELEVANCE:
      Feline stromelysin-1 contains all the conserved regions typically found in
      members of the MMP family. Activity of stromelysin-1 has been implicated in a
      wide number of physiologic and pathologic processes. Identification of this gene
      may lead to the development of useful reagents to assist with diagnosis and
      management of neoplastic diseases in cats.

PMID- 14974580
TI  - In vitro investigation of the effects of nonsteroidal anti-inflammatory drugs,
      prostaglandin E2, and prostaglandin F2alpha on contractile activity of the third
      compartment of the stomach of llamas.
AB  - OBJECTIVE: To determine the in vitro effect of prostaglandin (PG) E2, PGF2alpha,
      and the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin, ketoprofen,
      and nabumetone on the contractile strength of the circular smooth muscle layer of
      the third compartment of the stomach of llamas. SAMPLE POPULATION: Specimens of
      the third compartment obtained from 5 healthy adult llamas. PROCEDURE: Full
      thickness tissue samples were collected from the third compartment immediately
      after euthanasia. Specimens were cut into strips oriented along the circular
      muscle layer and mounted in a tissue bath system. Incremental amounts of
      ketoprofen, nabumetone, indomethacin, PGE2, and PGF2alpha were added, and
      contractile strength (amplitude of contractions) was recorded. RESULTS:
      Generally, PGE2 reduced contractile strength of the circular smooth layer of the
      third compartment, whereas PGF2alpha, increased the strength of contractions. The
      activity of the NSAIDs was generally excitatory in a concentration-dependent
      manner, although significant changes were induced only by administration of
      indomethacin. CONCLUSIONS AND CLINICAL RELEVANCE: On isolated smooth muscle
      strips of the third compartment of llamas, exogenous PGE2 and PGF2alpha had a
      variable effect on contractile strength. Administration of the NSAIDs did not
      inhibit contractility and would not be likely to induce stasis of the third
      compartment in the absence of an underlying disease process.

PMID- 14974581
TI  - Effects of infusion of adenosine triphosphate-magnesium chloride on
      cardiopulmonary and clinicopathologic variables, cytokine activity, and
      endothelin concentration in horses administered a low dose of endotoxin.
AB  - OBJECTIVE: To evaluate systemic effects of i.v. infusion of ATP-MgCl2 subsequent
      to infusion of a low dose of endotoxin in horses. ANIMALS: 12 adult horses.
      PROCEDURE: Horses were administered endotoxin (lipopolysaccharide [LPS]) or
      saline (0.9% NaCl) solution i.v., during a 30-minute period. Immediately
      thereafter, horses in each group were infused i.v. with ATP-MgCl2 or saline
      solution. Two weeks later, horses were administered the opposite solution (LPS or
      saline solution), but it was followed by the same infusion as 2 weeks previously
      (ie, ATP-MgCl2 or saline solution). Cardiopulmonary and clinicopathologic
      variables, cytokine activity, and endothelin (ET) concentrations were recorded.
      RESULTS: IV infusion of ATP-MgCl2 after administration of a low dose of endotoxin
      failed to attenuate the cardiopulmonary, clinicopathologic, and cytokine
      alterations that develop secondary to endotoxin exposure. The combination of LPS
      and ATP-MgCl2 potentiated pulmonary hypertension, leukopenia, and neutropenia
      when compared with the combination of LPS and saline solution. The combination of
      LPS and ATP-MgCl2 resulted in thrombocytopenia. Endothelin concentration was
      increased in jugular venous and pulmonary arterial plasma in horses receiving LPS
      and ATP-MgCl2. Similar increases were not observed with LPS and saline solution.
      CONCLUSIONS AND CLINICAL RELEVANCE: Administration of ATP-MgCl2 did not protect
      horses from systemic effects of experimentally induced endotoxemia. Furthermore,
      the use of ATP-MgCl2 during endotoxemia may worsen the cardiopulmonary and
      clinicopathologic status of affected horses. Because ATP and other adenine
      nucleotides are released from cells during shock, their potential role in the
      development of hemodynamic derangements, leukocyte adherence, and coagulopathies
      during endotoxemic episodes warrants further investigation.

PMID- 14974582
TI  - Effects of insulin-like growth factor-II on the mitogenic and metabolic
      activities of equine articular cartilage with and without interleukin 1-beta.
AB  - OBJECTIVE: To investigate the effects of insulin-like growth factor-II (IGF-II)
      on DNA and glycosaminoglycan (GAG) synthesis and the expression of matrix-related
      genes in equine articular cartilage explants and chondrocytes, respectively, with
      and without interleukin 1-beta (IL1-beta). SAMPLE POPULATION: Articular cartilage
      from 12 adult horses. PROCEDURE: Articular cartilage was incubated in standard
      media with and without equine IL1-beta (10 ng/mL) containing various
      concentrations of IGF-II for 72 hours. Synthesis of DNA and GAG was determined by
      incorporation of thymidine labeled with radioactive hydrogen (3H) and sulfate
      labeled with radioactive sulfur (35S), respectively. Total GAG content of the
      explants and spent media was determined by use of the 1,9-dimethylmethylene blue
      assay. Northern blots of RNA from cultured equine articular cartilage
      chondrocytes were hybridized with cDNA of major matrix molecules. RESULTS:
      Insulin-like growth factor-II stimulated DNA and GAG synthesis at concentrations
      of 25 and 50 ng/mL, respectively. In cartilage explants conditioned with IL1
      beta, IGF-II stimulated DNA and GAG synthesis at concentrations of 500 and 50
      ng/mL, respectively. Insulin-like growth factor-II had no effect on total GAG
      content as determined by the 1,9-dimethylmethylene blue assay. No specific
      effects on steady-state levels of messenger RNAs were observed. CONCLUSIONS AND
      CLINICAL RELEVANCE: Insulin-like growth factor-II stimulated DNA and GAG
      synthesis in equine adult cartilage and may have potential application in vivo.

PMID- 14974583
TI  - Blood pressure assessment in healthy cats and cats with hypertensive retinopathy.
AB  - OBJECTIVE: To determine whether there was an association between hypertensive
      retinopathy and high systolic, diastolic, and mean arterial blood pressures in
      cats. ANIMALS: 181 cats. PROCEDURE: Systolic, diastolic, and mean arterial blood
      pressures were measured by use of a noninvasive oscillometric technique. The
      range of blood pressure measurements in healthy cats from various age groups was
      determined. Associations among systolic, diastolic, and mean arterial blood
      pressure; hypertensive retinopathy; hyperthyroidism; left ventricular cardiac
      hypertrophy; chronic renal failure; and serum biochemical abnormalities were
      determined. RESULTS: All blood pressure measurements increased with age in
      healthy cats. The frequency of hypertensive retinopathy also increased with age
      and with blood pressure, and hypertensive retinopathy was particularly found in
      cats with systolic blood pressures > 168 mm Hg. There was an increased risk for
      hypertensive retinopathy in cats that were female, > 10 years old, and neutered.
      The risk of chronic renal failure also increased as blood pressure, particularly
      systolic blood pressure, increased. CONCLUSIONS AND CLINICAL RELEVANCE:
      Hypertensive retinopathy was common in cats > or = 10 years of age and was
      associated with systolic blood pressures > 168 mm Hg when measured by the
      noninvasive oscillometric technique.

PMID- 14974584
TI  - Erectile dysfunction in the patient with diabetes mellitus.

PMID- 14974585
TI  - Translating imaging into health: the Radiology Alliance for Health Services
      Research.

PMID- 14974586
TI  - What is evidence-based medicine?
AB  - RATIONALE AND OBJECTIVES: In this review article, we present the definition and
      useful concepts of evidence-based medicine (EBM). The principles of EBM are
      provided and major steps of practicing EBM are described. MATERIALS AND METHODS:
      We emphasize the importance of the Cochrane Collaboration (see
      http://www.cochrane.org), which initiated the research and practice in this area.
      Because it can be difficult to systematically access and review individual
      research studies, it is often useful to focus on a critical overview of clinical
      trials by conducting a meta-analysis. RESULTS: Useful literature and resources
      related to meta-analysis are provided. CONCLUSION: Statistical methods for
      evaluating radiologic diagnostic performances derived from meta-analysis are
      summarized, with a special focus on summary outcomes measures.

PMID- 14974587
TI  - Critically assessing the radiology literature.
AB  - To practice evidence-based radiology, knowledge of how to critically assess the
      literature is vital. This article outlines how to evaluate the radiology
      literature by asking these questions: Is it true?, Is it relevant?, and Is it
      sufficient? Clinical examples are used to explain several important causes of
      bias, as well as to clarify how these biases can affect the relevance of a
      particular study to a given clinical situation. Finally, discussion centers on
      the strength of evidence for both positive and negative findings in a research
      study.

PMID- 14974588
TI  - Introduction to cost-effectiveness analysis in radiology: principles and
      practical application.
AB  - The objectives of this paper are to provide the framework for understanding the
      principles of cost-effectiveness analysis and to practically apply these
      principles when reading a cost-effectiveness article. The article focuses on the
      application of these concepts to radiology procedures. To illustrate these
      concepts, we will use a hypothetical case of a physician deciding on the most
      cost-effective method for initially evaluating a 60-year-old menopausal woman who
      complains of new vaginal bleeding.

PMID- 14974589
TI  - Getting started in radiology research: asking the right question and identifying
      an appropriate study population.
AB  - Establishing a solid research question and appropriate methodology for selecting
      study participants forms the basis for good study design. For example, the
      diminished reputation of retrospective studies can be traced to problems with
      defining the research question and study population. In retrospective studies,
      one sets out to use data collected in the past, usually for a purpose other than
      the research study being executed. Therefore, the investigator does not have the
      opportunity to tailor the data collection to the research question or control the
      selection of study participants. The potential mismatch between the collected
      data, the intended research question, and the intended study population is a
      major cause, if not the main cause of bias in retrospective studies. Prospective
      studies offer an investigator the opportunity to collect all data relevant to the
      research question and to control the selection of study participants to minimize
      selection bias. It is up to the investigator to take full advantage of this
      opportunity through adequate planning of the study. Retrospective studies are not
      without merit, however, because they may be the only practical way to study rare
      diseases or patient outcomes. Whatever the study design, problems in defining the
      study population should either be addressed in the study or stated as a
      limitation of the study. In this article, I have discussed the importance of
      considering the research question and selection of study participants and have
      provided some basic related advice (Table). These two aspects of clinical
      research have a substantial effect on whether a study's results are
      scientifically worthwhile and ultimately useful to others. Attention to these
      issues should be helpful to the various roles involved in the life of a study:
      the investigator planning the study, the reviewer of the resulting manuscript,
      and the reader of the published research article.

PMID- 14974590
TI  - Continuous quality improvement for radiologists.
AB  - Continuous quality improvement methods provide a relatively new way to improve
      quality in healthcare by using a systems approach with key features of customer
      mindedness, data collection, experimentation, and teamwork. CQI is not meant to
      solve simple problems but is increasingly applied in our complex healthcare
      organizations. In fact, CQI is as much philosophy as it is both a qualitative and
      quantitative method to assess quality. This review describes the general methods
      and potential application for radiologists.

PMID- 14974591
TI  - Screening issues for radiologists.

PMID- 14974592
TI  - A cost-minimizing diagnostic methodology for discrimination between neoplastic
      and non-neoplastic brain lesions: utilizing a genetic algorithm.
AB  - RATIONAL AND OBJECTIVES: The purpose of this study was to make an improvement in
      the performance of a logistic regression model in predicting the presence of
      brain neoplasia with magnetic resonance spectroscopy data by using a new approach
      for logistic regression coefficient estimation. This new approach, termed cost
      minimizing (C-min), introduced by one of the authors (Chetty), uses the cost
      function for prediction outcomes to estimate model coefficients and the
      prediction decision rule. To do this requires use of a genetic algorithm.
      MATERIALS AND METHODS: Consecutive patients with suspected brain neoplasms or
      recurrent neoplasia referred for magnetic resonance spectroscopy were enrolled
      once a final diagnosis was established by histopathology or clinical course,
      laboratory data, and serial imaging. For the same magnetic resonance spectroscopy
      explanatory (input) variables, logistic regression models were constructed with
      conventional and C-min coefficient estimates, and sensitivity and specificity
      outcomes were compared at alternative probability threshold levels. RESULTS: The
      C-min approach dominated the conventional approach in 14 of 18 trials, in that C
      min had either fewer of both false negatives and false positives, or it had the
      same number of one type, and less of the other type of diagnostic error. C-min
      was always less costly. CONCLUSION: The C-min approach to logistic or other
      regression model estimation may be a step forward in reducing the cost and,
      often, the errors of diagnostic (and treatment) processes. However, this new
      approach must be validated on larger and more varied datasets, and its
      statistical performance characteristics determined before it can be implemented
      as a practical clinical tool.

PMID- 14974593
TI  - Statistical validation of image segmentation quality based on a spatial overlap
      index.
AB  - RATIONALE AND OBJECTIVES: To examine a statistical validation method based on the
      spatial overlap between two sets of segmentations of the same anatomy. MATERIALS
      AND METHODS: The Dice similarity coefficient (DSC) was used as a statistical
      validation metric to evaluate the performance of both the reproducibility of
      manual segmentations and the spatial overlap accuracy of automated probabilistic
      fractional segmentation of MR images, illustrated on two clinical examples.
      Example 1: 10 consecutive cases of prostate brachytherapy patients underwent both
      preoperative 1.5T and intraoperative 0.5T MR imaging. For each case, 5 repeated
      manual segmentations of the prostate peripheral zone were performed separately on
      preoperative and on intraoperative images. Example 2: A semi-automated
      probabilistic fractional segmentation algorithm was applied to MR imaging of 9
      cases with 3 types of brain tumors. DSC values were computed and logit
      transformed values were compared in the mean with the analysis of variance
      (ANOVA). RESULTS: Example 1: The mean DSCs of 0.883 (range, 0.876-0.893) with
      1.5T preoperative MRI and 0.838 (range, 0.819-0.852) with 0.5T intraoperative MRI
      (P < .001) were within and at the margin of the range of good reproducibility,
      respectively. Example 2: Wide ranges of DSC were observed in brain tumor
      segmentations: Meningiomas (0.519-0.893), astrocytomas (0.487-0.972), and other
      mixed gliomas (0.490-0.899). CONCLUSION: The DSC value is a simple and useful
      summary measure of spatial overlap, which can be applied to studies of
      reproducibility and accuracy in image segmentation. We observed generally
      satisfactory but variable validation results in two clinical applications. This
      metric may be adapted for similar validation tasks.

PMID- 14974594
TI  - A software application for multiattribute utility models.
AB  - RATIONALE AND OBJECTIVES: A software application for the building of preference
      weighted quality of life instruments was constructed. The purpose of this
      application is to make the process of building such instruments with
      multiattribute utility (MAU) methods more accessible to physician investigators.
      Our application, "multiattribute outcomes evaluator" or "MOE," could facilitate
      the use of such methods for constructing disease-specific instruments for
      assessing the cost-effectiveness of new treatments. MOE could also be useful for
      building outcomes measures that are intended to aid individual decision making,
      assessment of patient satisfaction with care, or measuring of multiattribute
      outcomes that do not need to be scaled for cost-effectiveness analysis. MATERIALS
      AND METHODS: MOE was programmed in Visual Basic and runs atop a Microsoft Access
      data base. Data from groups or individuals can be stored, and valuations of
      health states can be performed using standard gambles and rating scale methods.
      Solutions to MAU models with multiplicative or additive utility independence are
      possible with this application. RESULTS: Initial tests of the program algorithms
      have been successful. CONCLUSION: We anticipate The MOE approach to MAU modeling
      will be a useful tool for health services researchers.

PMID- 14974595
TI  - Expect the unexpected: thoughts, insights and musing about research in radiology.

PMID- 14974596
TI  - Lee Lusted: a pioneer in radiology health services research.

PMID- 14974597
TI  - Quantitative perfusion map of malignant liver tumors, created from dynamic
      computed tomography data.
AB  - RATIONALE AND OBJECTIVES: To apply perfusion computed tomography (CT) technique
      to variable malignant liver tumors, and to define the usefulness of quantitative
      color mapping. MATERIALS AND METHODS: Perfusion CT images were created for 36
      malignant liver tumors in 28 patients (age, 66.4 +/- 10.1 years; range, 48-85)
      with metastatic liver tumors (n = 17; nine colorectal carcinomas, eight other
      malignant tumors) and hepatocellular carcinomas (n = 11). A single-slice dynamic
      CT was performed after an intravenous bolus injection of 40 mL of contrast
      material (320 mgI/mL) with 8 mL/sec. The parameters were calculated pixel-by
      pixel using maximum slope method, and quantitative maps of arterial and portal
      perfusion were created. In four patients who underwent transcatheter arterial
      chemoembolization, perfusion CT was performed before and after transcatheter
      arterial chemoembolization. RESULTS: In all patients, liver tumors were shown as
      hypervascular lesions on arterial perfusion CT. The average arterial perfusion
      value of the metastatic tumors from the colorectal carcinomas was 0.67 +/- 0.33
      mL/min/mL, and that of hepatocellular carcinomas was 0.94 +/- 0.26 mL/min/mL (P =
      .03). The other metastatic tumors from various primary tumors showed a wide range
      (0.19-1.45 mL/min/mL) of arterial perfusion. Arterial perfusion of the liver
      tumors was obviously decreased after successful transcatheter arterial
      chemoembolization. In 12 of 15 tumors, in which portal perfusion CT images could
      be created, region-of-interest analysis showed no portal perfusion in the tumors.
      In two cases, decreased portal perfusion in the segments, which malignant tumors
      involved, was demonstrated. CONCLUSION: Perfusion CT can provide quantitative
      information about arterial and portal perfusion of liver tumors, combined with
      good anatomic detail in one image. This technique has a potential to evaluate the
      angiogenesis of liver tumors, to show secondary changes in perfusion, such as
      decreased portal perfusion in apparently normal liver adjacent to metastases, and
      to monitor the therapeutic response in vivo.

PMID- 14974599
TI  - Consistency of reporting basic characteristics of lung nodules and masses on
      computed tomography.
AB  - RATIONALE AND OBJECTIVES: To assess the consistency of chest computed tomography
      (CT) reports in describing basic characteristics of lung nodules and masses.
      MATERIALS AND METHODS: We retrospectively identified 107 consecutive patients
      with preoperative chest CT scans before resection of a lung nodule or mass over a
      4-year period within a single institution. There were 54 men and 53 women with a
      mean age of 64 years (range, 37-86) years. The CT scans were reported by a cohort
      of 20 board-certified radiologists, three of whom reviewed more than 10 CT scans
      (n = 60 exams). The CT reports were reviewed for lesion characteristics including
      size, location, and description of margins, presence or absence of calcification,
      fat and cavitation, and the diagnosis or differential diagnosis. Pathology
      reports were reviewed for the same characteristics and the final diagnosis. Both
      CT and pathologic reports of emphysema were noted in lobectomy specimens. The
      differences between the interpreting radiologists were also sought. RESULTS: A
      diagnosis or differential diagnosis was provided in 90% (96/107) of CT reports.
      The diagnosis of bronchogenic carcinoma was made in 78% (59/76) of those with
      bronchogenic carcinoma, compared with 65% (20/31) of those with other diagnoses
      (P = NS). Radiologists described the margins of the nodule or mass in 64%
      (68/107) of cases, similar in frequency to 66% of pathologists (71/107).
      Radiologic description of an irregular/spiculated margins predicted bronchogenic
      carcinoma in 86% of cases (42/49), while a smooth/lobulated margins predicted a
      diagnosis other than bronchogenic carcinoma in 58% (11/19; P < .05). The presence
      or absence of calcification was noted in 7% (5/76) of cases of bronchogenic
      carcinoma and 32% (10/31) of those with other diagnoses (P < .05, chi square).
      Both radiologists and pathologists consistently reported the size of the lesions
      with a correlation coefficient between radiology and pathology reports of 0.88.
      CT reporting of the characteristics of the lesion did not differ among lesions of
      different sizes. There was no significant difference between major reporters
      (more than 10 cases) in this study. Emphysema in the surrounding lung was
      reported in 25% (20/81) of radiology and 38% (31/81) of pathology reports (P =
      NS). CONCLUSION: This series demonstrates a lack of consistent reporting of the
      margins of resected lung nodules both on CT and on pathologic specimens. The
      presence or absence of calcification was inconsistently reported, although more
      frequently noted in diagnoses other than bronchogenic carcinoma. As large-scale
      CT screening for lung cancer becomes more common, radiologists should prioritize
      developing and adopting standardized reporting criteria for the CT evaluation of
      lung nodules.

PMID- 14974598
TI  - Comparison of single-shot echo-planar and line scan protocols for diffusion
      tensor imaging.
AB  - RATIONALE AND OBJECTIVES: Both single-shot diffusion-weighted echo-planar imaging
      (EPI) and line scan diffusion imaging (LSDI) can be used to obtain magnetic
      resonance diffusion tensor data and to calculate directionally invariant
      diffusion anisotropy indices, ie, indirect measures of the organization and
      coherence of white matter fibers in the brain. To date, there has been no
      comparison of EPI and LSDI. Because EPI is the most commonly used technique for
      acquiring diffusion tensor data, it is important to understand the limitations
      and advantages of LSDI relative to EPI. MATERIALS AND METHODS: Five healthy
      volunteers underwent EPI and LSDI diffusion on a 1.5 Tesla magnet (General
      Electric Medical Systems, Milwaukee, WI). Four-mm thick coronal sections,
      covering the entire brain, were obtained. In addition, one subject was tested
      with both sequences over four sessions. For each image voxel, eigenvectors and
      eigenvalues of the diffusion tensor were calculated, and fractional anisotropy
      (FA) was derived. Several regions of interest were delineated, and for each, mean
      FA and estimated mean standard deviation were calculated and compared. RESULTS:
      Results showed no significant differences between EPI and LSDI for mean FA for
      the five subjects. When intersession reproducibility for one subject was
      evaluated, there was a significant difference between EPI and LSDI in FA for the
      corpus callosum and the right uncinate fasciculus. Moreover, errors associated
      with each FA measure were larger for EPI than for LSDI. CONCLUSION: Results
      indicate that both EPI- and LSDI-derived FA measures are sufficiently robust.
      However, when higher accuracy is needed, LSDI provides smaller error and smaller
      inter-subject and inter-session variability than EPI.

PMID- 14974600
TI  - The roles of the board examination.

PMID- 14974601
TI  - Comparative dosimetry of BEIR VI revisited.
AB  - The BEIR VI Committee applied recent developments in the comparative dosimetry of
      radon exposures in mines and homes to evaluate the so-called K-factor used to
      extrapolate the excess relative risk of lung cancer determined for underground
      uranium miners to exposures in homes. This paper describes methodological aspects
      of these developments that were specified ambiguously in the BEIR VI report.
      Specifically, in the section dealing with dosimetry (Appendix B of the BEIR VI
      report), the K-factor was unusually defined in terms of exposure to radon gas
      (K(gas)), and not in terms of exposure to potential alpha energy (K). An
      incorrect value of unity was calculated for K(gas). This implies a value of 0.44
      for K. In this paper, we describe how application of the ICRP Publication 66 lung
      and dosimetric models to evaluate the regional lung dose per unit exposure to
      potential alpha-energy in mines and homes yields the value of K = unity. This
      confirms the BEIR VI Committee's choice of K = 1 for application in their risk
      extrapolation model. The paper also reviews the use of doses to specific sub
      cellular targets in the evaluation of K. This yields a somewhat greater
      divergence in the corresponding estimates of K, but again an overall average
      value of K = unity. The paper describes the methods used to calculate alpha
      particle hit probabilities for specific subcellular targets, and the resulting
      estimates of single- and multiple-hit probabilities obtained for exposures in
      mines and homes, as a function of the respective exposure rates.

PMID- 14974602
TI  - Dose due to scattered radiation in external radiotherapy: a prostate cancer case
      history.
AB  - One of the authors was subjected to external radiotherapy with 6 MeV photons to
      treat a prostate cancer. The dose due the radiation scattered by the target was
      measured by means of pen dosemeters distributed along the body. Subsequently,
      both the equivalent dose delivered to some organs and the effective dose
      delivered to the body, due to scattering only, were evaluated.

PMID- 14974603
TI  - Calibration of dosemeters used in mammography with different X ray qualities:
      EUROMET project no. 526.
AB  - The effect of different X ray radiation qualities on the calibration of
      mammographic dosemeters was investigated within the framework of a EUROMET
      (European Collaboration in Measurement Standards) project. The calibration
      coefficients for two ionization chambers and two semiconductor detectors were
      established in 13 dosimetry calibration laboratories for radiation qualities used
      in mammography. They were compared with coefficients for other radiation
      qualities, including those defined in ISO 4037-1, with first half value layers in
      the mammographic range. The results indicate that the choice of the radiation
      quality is not crucial for instruments with a small energy dependence of the
      response. However, the radiation quality has to be chosen carefully if
      instruments with a marked dependence of their response to the radiation energy
      are calibrated.

PMID- 14974604
TI  - Chromosome aberrations induced in human lymphocytes by heavy charged particles in
      track segment mode.
AB  - Human blood was irradiated with accelerated ions: 20 MeV 4He, 425 MeV 12C and
      1480 MeV and 996 MeV 16O. For each ion, the blood was exposed to a range of doses
      as thin specimens in the track segment mode, so that irradiations took place at
      nearly constant LETs of 31.4, 61, 52 and 69 keV microm(-1), respectively.
      Lymphocytes were cultured to the first in vitro metaphase, analysed for
      chromosomal damage and the dicentric aberration frequencies fitted to the linear
      quadratic model of dose-response. For these high LET radiations, the linear
      (alpha) yield coefficient predominated and increased with LET, at least up to 60
      keV microm(-1). Apart from the 996 MeV oxygen ions, the data indicated the
      presence of a quadratic (beta) coefficient, statistically consistent with values
      obtained with low LET radiations. However, the associated uncertainties on the
      measured beta values were large, illustrating the general problem that beta is
      more difficult to measure against a dominating and ever-increasing alpha term.
      The existence or otherwise of a beta component of the dose-response at these
      radiation qualities has important consequences for modelling mechanisms of
      aberration induction by radiation.

PMID- 14974605
TI  - Short-term temporal variations of soil gas radon concentration and comparison of
      measurement techniques.
AB  - Short-term temporal variations of soil gas radon concentration have been studied
      using different measuring techniques--instantaneous methods (grab sampling) using
      Lucas cells, continuous monitors, and integral nuclear track-etch detectors. A
      relatively low variability appeared during a 72-h follow-up. Different temporal
      changes were observed by using different methods. A substantial part of these
      changes was probably caused by fluctuations and errors connected with measuring
      methods themselves and did not reflect real variations of the measured parameter.

PMID- 14974606
TI  - Patient effective dose and radiogenic risks from fluoroscopically assisted
      surgical reconstruction of femoral fractures.
AB  - The objectives were to assess patient effective radiation dose from
      fluoroscopically guided surgical reconstruction of femoral fractures and provide
      normalized data for the estimation of patient effective dose and risks associated
      with such procedures performed in any laboratory. The fluoroscopic control
      required during surgical reconstruction of femoral fractures was classified into
      two types identified by beam orientation, i.e., posterior-anterior (PA) and
      lateral crosstable (LC) exposures. The duration and the dose area product (DAP)
      of each exposure were monitored in 24 patients with femoral fractures. Patient
      dose per DAP unit and per minute of fluoroscopy were measured at 14
      radiosensitive organs/tissues using an anthropomorphic phantom and
      thermoluminescence dosimetry. The typical effective dose to patients with femoral
      fracture treated surgically in our institution was 11.6-21.7 microSv. This
      effective dose is estimated to cause an excess of 1.4 fatal cancers per million
      patients treated, and an excess of 0.4 hereditary disorders per million of
      births. Induction of deterministic skin injuries to treated patients is highly
      improbable at the dose levels found in this study. Patient effective dose and
      associated risks from a typical fluoroscopically guided surgical fixation of
      femoral fracture are low. However, they may be significantly elevated if treated
      patients are young individuals and/or the fluoroscopic exposure is prolonged. The
      present data may be used to determine effective dose to patients undergoing
      surgical reconstruction of femoral fracture in any institution.

PMID- 14974607
TI  - Dose rate assessment of terrestrial gamma radiation in the Delta region of
      Nigeria.
AB  - In situ gamma spectroscopy has been employed to characterise natural radiation in
      the soil at 32 locations in the Delta region of Nigeria. The outdoor gamma dose
      rates in the air due to 40K, 238U and 232Th in the soil were 1.5 +/- 0.9 nGy h(
      1), 6.9 +/- 1.6 nGy h(-1) and 16.3 +/- 3.1 nGy h(-1) respectively. The estimated
      total annual outdoor effective dose to the people in the region was 31.6 microSv
      y(-1).

PMID- 14974608
TI  - Developments in the synthesis of LiF:Mg,Cu,Na,Si TL material.
AB  - A procedure for synthesis of the highly sensitive pellet-type LiF:Mg,Cu,Na,Si
      thermoluminescent (TL) detector has been newly developed. It was found that the
      optimum concentrations of dopants for a pellet-type LiF:Mg,Cu,Na,Si TL detector
      were found to be Mg: 0.2 mol %, Cu: 0.05 mol %, Na: 0.9 mol%, and Si: 0.9 mol%.
      The TL sensitivity of this new detector was about 30 times higher than that of
      the TLD-100 by light integration measurements. Reusability study of the detector
      was carried out for 10 cycles. The results show that the coefficients of
      variation for each detector separately did not exceed 0.016, and that for all 10
      detectors collectively was 0.0054.

PMID- 14974609
TI  - The validation of organ dose calculations using voxel phantoms and Monte Carlo
      methods applied to point and water immersion sources.
AB  - The Monte Carlo program 'Visual Monte Carlo-dose calculation' (VMC-dc) uses a
      voxel phantom to simulate the body organs and tissues, transports photons through
      this phantom and reports the absorbed dose received by each organ and tissue
      relevant to the calculation of effective dose as defined in ICRP Publication 60.
      This paper shows the validation of VMC-dc by comparison with EGSnrc and with a
      physical phantom containing TLDs. The validation of VMC-dc by comparison with
      EGSnrc was made for a collimated beam of 0.662 MeV photons irradiating a cube of
      water. For the validation by comparison with the physical phantom, the case
      considered was a whole body irradiation with a point 137Cs source placed at a
      distance of 1 m from the thorax of an Alderson-RANDO phantom. The validation
      results show good agreement for the doses obtained using VMC-dc and EGSnrc
      calculations, and from VMC-dc and TLD measurements. The program VMC-dc was then
      applied to the calculation of doses due to immersion in water containing gamma
      emitters. The dose conversion coefficients for water immersion are compared with
      their equivalents in the literature.

PMID- 14974610
TI  - Polyprenyl-hydroquinones and -furans from three marine sponges inhibit the cell
      cycle regulating phosphatase CDC25A.
AB  - The CDC25 phosphatases regulate the cell division cycle by controlling the
      activity of cyclin-dependent kinases. While screening for inhibitors of
      phosphatases among natural products we repeatedly found that some polyprenyl
      hydroquinones and polyprenyl-furans (furanoterpenoids) (furospongins,
      furospinosulins) were potent CDC25 phosphatase inhibitors. These compounds were
      extracted, isolated and identified independently from three sponge species
      (Spongia officinalis, Ircinia spinulosa, Ircinia muscarum), collected at
      different locations in the Mediterranean Sea. The compounds were inactive on the
      Ser/Thr phosphatase PP2C-alpha and on three kinases (CDK1, CDK5, GSK-3),
      suggesting that some potent and selective CDC25 phosphatase might be designed
      from these initial structures.

PMID- 14974611
TI  - Negative ion FAB mass spectroscopy of some ribose alkylated 5'-UMP derivatives.
AB  - Characteristic fragment ions obtained in Fast atom bombardment (FAB) mass
      spectroscopy of ribose alkylated Uridine 5'-monophosphate (5'-UMP) derivatives in
      negative ion mode are described. All the compounds examined exhibited either [M]-
      or quasimolecular ion [M - H]- the fragmentations can be used to characterize
      these nucleotides.

PMID- 14974612
TI  - Diterpene derivative and chromone from Hypericum perforatum.
AB  - A novel diterpene derivative, 5-methyl-5-(4,8,12-trimethyl-tridecyl)-dihydro
      furan-2-one (1) and a new chromone, 5-hydroxy-7-methoxy-3-methyl-chromen-4-one
      (2), along with a known compound, phytol (3) have been isolated from the aerial
      parts of Hypericum perforatum. Their structures were established on the basis of
      spectroscopic analysis and by comparison with published values.

PMID- 14974613
TI  - Synthesis, antifungal, and phytotoxic effects of some benzopyrone derivatives.
AB  - Syntheses of benzopyrones 1, 13, and their derivatives, as well as their
      phytotoxic (in vitro) and antifungal (in vitro) screening was carried out.
      Compounds 2, 7, 8, and 10 showed significant phytotoxic activity, whereas 3, 8,
      10, and 12 exhibited significant antifungal (in vitro) activity.

PMID- 14974614
TI  - Phenolic components of Olea europaea--isolation of tyrosol derivatives.
AB  - A new tyrosol derivative, the oleic ester of tyrosol, was isolated from fruits of
      Olea europaea, Cassanese cultivar. Salidroside, the known glucosyl derivative of
      thyrosol, was isolated from the Carolea cultivar.

PMID- 14974615
TI  - A new tetracyclic triterpene from the latex of Euphorbia nerifolia.
AB  - A new tetracyclic triterpene 9,19-cyclolanost-22(22'), 24-diene-3beta-ol, named
      as nerifoliene (2) along with euphol (1) were isolated from the fresh latex of
      Euphorbia nerifolia. Their structures were elucidated on the basis of spectral
      (IR, 1H and 13C NMR, FAB and EI Mass) data.

PMID- 14974616
TI  - 1,3-dimethyl-8-oxoisoguanine, a new purine from the New Zealand ascidian
      Pseudodistoma cereum.
AB  - A new purine, 1,3-dimethyl-8-oxoisoguanine (2) was isolated from the New Zealand
      ascidian Pseudodistoma cereum. The structure of 2 was elucidated by the use of
      standard spectroscopic techniques, including natural abundance 1H-15N 2D NMR.

PMID- 14974617
TI  - Halogenated secondary metabolites from Laurencia obtusa.
AB  - A new sesquiterpene (1), and a halogenated C15 acetogenin (2), a stereoisomer of
      neoisoprelaurefucin were isolated from Laurencia obtusa. Four known compounds
      laurencienyne (3), rogiolenyne B (4), obtusenol (5), and (3E)-dactomelyne (6)
      were also isolated from this alga. Rogiolenyne B (4) and (3E)-dactomelyne (6)
      were found for the first from this species. The structures of these compounds
      were elucidated by spectroscopic methods. The unambiguous assignments of the 1H
      and 13C NMR spectral data of (5) and 13C NMR data of (6) were also reported for
      the first time.

PMID- 14974618
TI  - Cytotoxicity of in vitro produced podophyllotoxin from Podophyllum hexandrum on
      human cancer cell line.
AB  - Podophyllotoxin was produced by cell culture of Podophyllum hexandrum under in
      vitro culture conditions. A maximum of 4.26 mg/L of podophyllotoxin was produced
      when P. hexandrum was cultivated in 3 L stirred tank bioreactor. The compound
      extracted from the cell culture was applied to the human breast cancer cell line
      (MCF-7) and 1 nM podophyllotoxin was able to inhibit the growth of the cancer
      cells by 50%. The most profound inhibitory effect of podophyllotoxin was observed
      when it was applied in the beginning of cell growth.

PMID- 14974619
TI  - Resurgence of natural colourants: a holistic view.
AB  - Today, natural colourants are emerging globally, leaving synthetic colourants
      behind in the race, due to the realisation that are safer and ecofriendly in
      nature. In this context, a brief review of natural colourant sources, their
      classification, chemical constituents responsible for producing different
      colours, its activities and effect of different mordants on the hue is discussed.

PMID- 14974620
TI  - A new flavonoid and sulphur-containing amides from Glycosmis chlorosperma.
AB  - A new flavonoid, dihydroglychalcone-A, was isolated from the leaves extract of
      Glycosmis chlorosperma in addition to two known sulphur-containing amides,
      dambullin and gerambullin. The structure of the new compound was assigned as 2'
      hydroxy-4,6'-dimethoxy-3',4'-(2",2"-dimethylpyrano)dihydrochalcone. The extract
      of the leaves was also found to exhibit antimicrobial and cytotoxic activities.

PMID- 14974621
TI  - Cytotoxic isoquinoline quinones from sponges of the genus Petrosia.
AB  - Bioassay-guided fractionation of two Philippine sponges of the genus Petrosia has
      resulted in the isolation of the novel natural product cribrostatin 7 (1) and the
      known compounds renierone (2) and O-demethylrenierone (3). The structures of
      these isoquinoline quinones were determined by interpretation of spectroscopic
      data. Compounds 1, 2 and 3 were cytotoxic against the HCT 116 human colon
      carcinoma cell line with IC50 values of 45, 24 and 34 microg/mL, respectively.

PMID- 14974622
TI  - A new method of synthesis and antibacterial activity evaluation of piper amides.
AB  - Several natural piper amides and their mimics were synthesized by developing a
      new strategy of amide formation. The piper amides were tested against both gram
      +ve and gram -ve bacterial strains and found that they are particularly more
      active against Staphylococcus aureus and Chromobacterium violaceum strains.

PMID- 14974623
TI  - Comparison of three procedures for initial fitting of compression hearing aids.
      II. Experienced users, fitted unilaterally.
AB  - This paper is the second in a series comparing three procedures for the initial
      fitting of multichannel compression hearing aids. The first paper reported the
      results for a group of 10 experienced hearing aid users fitted bilaterally. This
      paper reports the results for a different group of 10 experienced hearing aid
      users fitted unilaterally. The three procedures were: (1) CAMEQ, which aims to
      amplify speech so as to give equal loudness per critical band over the frequency
      range 500-5000 Hz, and to give similar overall loudness to normal over a wide
      range of speech levels; (2) CAMREST, which aims to amplify speech so as to
      restore normal specific loudness patterns, over a wide range of speech levels;
      and (3) DSL [i/o], which aims to map the dynamic range of normal-hearing people
      into the reduced dynamic range of hearing-impaired people, with full restoration
      of audibility. Each subject was fitted with one Danalogic 163D digital hearing
      aid, using each of the three fitting procedures in turn; the order was counter
      balanced across subjects. Prescribed insertion gains for 55 and 80 dB SPL input
      levels were verified using real-ear measurements. Immediately after fitting with
      a given procedure, and 1 week after fitting. the gains were adjusted, when
      required, by the minimum amount necessary to achieve acceptable fittings. On
      average, the adjustments were smallest for the CAMREST procedure, slightly larger
      for the CAMEQ procedure, and largest of all for DSL [i/o]. For the DSL [i/o] the
      gain changes were mostly negative, especially for high frequencies and the higher
      input level. After these gain adjustments, users wore the aids for at least 3
      weeks before speech reception thresholds (SRTs) for sentences in quiet and in
      steady and fluctuating background noise were measured. The APHAB questionnaire
      was also administered. The hearing aids were then refitted with the next
      procedure. SRTs and APHAB scores did not differ significantly between the three
      procedures. We conclude that the CAMEQ and CAMREST procedures provide a more
      appropriate initial fitting than DSL [i/o] for unilaterally experienced hearing
      aid wearers. Comparison with our earlier study based on bilateral fittings
      suggests that the preferred gains are similar for unilateral and bilateral
      fittings.

PMID- 14974624
TI  - Development and validation of an automatic speech-in-noise screening test by
      telephone.
AB  - To meet the need for an objective self-test for hearing screening. a new Dutch
      speech-in-noise test was developed. Digit triplets were used as speech material.
      The test was made fully automatic, was controlled by a computer, and can be done
      by telephone. It measures the speech reception threshold (triplet SRT(n)) using
      an adaptive procedure, in about 3 min. Our experiments showed no significant
      influence of telephone type or listening environment. Measurement errors were
      within 1 dB. which makes the test accurate. In additional experiments with
      hearing-impaired subjects (76 ears of 38 listeners), the new test was compared to
      the existing sentence SRT(n) test of Plomp and Mimpen, which is considered to be
      the standard. The correlation between both SRT(n)s was 0.866. As expected,
      correlations between the triplet SRT(n) test by telephone and average pure-tone
      thresholds are somewhat lower: 0.732 for PTA(0,5,1,2), and 0.770 for
      PTA(0,5,2,4). When proper SRT(n) values were chosen for distinguishing between
      normal-hearing and hearing-impaired subjects, the triplet SRT(n) test was found
      to have a sensitivity of 0.91 and a specificity of 0.93.

PMID- 14974625
TI  - Auditory brainstem evoked responses in insulin-dependent (ID) and non-insulin
      dependent (NID) diabetic subjects with normal hearing.
AB  - Hearing impairment has been reported to be one of the late complications of
      diabetes mellitus (DM), and the frequency varies. Previous data suggest that
      auditory brainstem potentials deteriorate long before the hearing impairment
      appears in patients with DM. Delay in neural conductance along the auditory
      pathway due to DM was assessed by means of auditory brainstem response (ABR) in
      43 patients with normal hearing in a controlled study. Patients were classified
      according to age, presence of neuropathy. metabolic control, and duration and
      type of DM. ABR recordings revealed that absolute latencies of waves I, III and V
      were prolonged significantly in the diabetic group when compared to the control
      group (p < 0.05). When two diabetic groups (insulin-dependent and non-insulin
      dependent) were compared with each other, the difference between the latency of
      wave I and the inter-peak latencies of I-III, III-V and I-V was not significant
      (p > 0.05). However, the difference between the latencies of waves III and V in
      the two diabetic groups was statistically significant. The duration of diabetes,
      blood glucose level and age were not associated with prolonged ABR latencies (p >
      0.05). Prolongation of latency of ABR in patients with DM should alert us to
      possible damage to the auditory nerve, and close follow-up is needed in these
      patients.

PMID- 14974626
TI  - Development of auditory processing in 6-12-year-old children: a longitudinal
      study.
AB  - The development of auditory processing in children was investigated in a
      longitudinal study. A group of 20 children with normal cognitive and language
      development underwent several auditory tests at the ages of 6, 7, 8, 10 and 12
      years. At the age of 10 years, three subjects were lost to follow-up, as was one
      more subject at the age of 12 years. The auditory performance of the children was
      compared to the performance of a group of 20 adults. The auditory test battery
      consisted of a speech-in-noise test, a filtered speech test, a binaural fusion
      test and two auditory sequencing tests. At the ages of 6, 7 and 8 years, data on
      the performance on an auditory word discrimination test, an auditory synthesis
      test, an auditory closure test and a number recall test were also obtained. All
      auditory tests except the speech-in-noise test showed a clear effect of age on
      the performance of children. Our data suggest that maturational effects play an
      important role in auditory processing (at least) up to an age of 12-13 years.
      Correlations between the tests are in general not indicative of large amounts of
      overlap between the different tests. Factor analysis shows that three factors
      account for 68-70% of explained variance, with the three factors contributing
      equally. A composite score obtained by averaging all (sub)test scores can be used
      next to the individual test scores to describe the development of auditory
      processing abilities in children.

PMID- 14974627
TI  - Diplacusis, hearing threshold and otoacoustic emissions in an episode of sudden,
      unilateral cochlear hearing loss.
AB  - Limited data are available on the relationship between diplacusis and otoacoustic
      emissions and sudden hearing threshold changes, and the detail of the mechanism
      underlying diplacusis is not well understood. Data are presented here from an
      intensively studied single episode of sudden, non-conductive, mild hearing loss
      with associated binaural diplacusis, probably due to a viral infection. Treatment
      with steroids was administered for 1 week. This paper examines the relationships
      between the hearing loss, diplacusis and otoacoustic emissions during recovery on
      a day-by-day basis. The hearing thresholds were elevated by up to 20 dB at 4kHz
      and upwards, and there was an interaural pitch difference up to 12% at 4 and 8
      kHz. There was also a frequency-specific change in transient evoked otoacoustic
      emission (TEOAE) and distortion-product otoacoustic emission (DPOAE) level. DPOAE
      level was reduced by up to 20 dB. with the greatest change seen when a stimulus
      with a wide stimulus frequency ratio was used. Frequency shifts in the 2f2-fi
      DPOAE fine structure corresponded to changes in the diplacusis. Complete recovery
      to previous levels was observed for TEOAE, DPOAE and hearing threshold. The
      diplacusis recovered to within normal limits after 4 weeks. The frequency shift
      seen in the DPOAE fine structure did not quite resolve, suggesting a very slight
      permanent change. The time-courses of TEOAE. diplacusis and hearing threshold
      were significantly different: most notably, the hearing threshold was stable over
      a period when the diplacusis deteriorated. This suggests that the cochlear
      mechanisms involved in diplacusis, hearing threshold and OAE may not be
      identical.

PMID- 14974628
TI  - Self-reported hearing difficulty and hearing impairment in Japanese people living
      in a community.
AB  - Nine hundred and eighteen people aged 40 years and over were examined to assess
      the relationship between self-reported hearing difficulty and hearing impairment
      at 1 kHz and 4kHz during annual health check-ups. After adjustment for potential
      confounding factors of self-reported hearing difficulty such as age, sex, noise
      exposure, ear disease and tinnitus. the odds ratios for self-reported hearing
      difficulty at 1 kHz compared with a hearing threshold of 30 dB were 1.74. 3.37
      and 4.97 for hearing thresholds of 40 dB, 50 dB, and over 50 dB, respectively (p
      value for trend = 0.003). At 4 kHz, the respective odds ratios for self-reported
      hearing difficulty were 1.53, 2.59 and 1.83 (p-value for trend = 0.012). These
      results suggest that self-reported hearing difficulty is closely associated with
      the severity of hearing impairment at 1 kHz and 4 kHz in a community-residing
      population and that people with hearing impairment at 1 kHz would be more
      sensitive to their hearing difficulty than those with hearing impairment at 4
      kHz.

PMID- 14974629
TI  - Comment on tinnitus in older adults from the Blue Mountains Study by Sindhusake
      et al and comparison with tinnitus data from the Epidemiology of Hearing Loss
      Study.

PMID- 14974630
TI  - Tribulations of transition care for the developmentally disabled.

PMID- 14974631
TI  - Neurological recovery in obstetric brachial plexus injuries: an historical cohort
      study.
AB  - An historical cohort study was conducted to investigate the rate and extent of
      neurological recovery in obstetric brachial plexus injury (OBPI) and to identify
      possible prognostic factors in a cohort of children with OBPI from birth to 7
      years. All children (n=56; 31 females, 25 males) with OBPI were evaluated at
      fixed time intervals by one examiner. They underwent a final neurological
      examination at a mean age of 3 years 10 months (range 1 to 7 years). Neurological
      outcome was not as favourable as is often reported: complete neurological
      recovery occurred in 37 out of 56 children (66%). In half of these there was
      delayed recovery, in which case complete neurological recovery was assessed from
      1.5 to 16 months of age (median age 6.5 months, SD 4.2 months). External rotation
      and supination were the last to recover and recovered the least. Although biceps
      function at three months was considered to be the best indicator for operative
      treatment, external rotation and supination were found to be better in predicting
      eventual complete recovery. Initial symptoms directly post partum were not found
      to be prognostic. Functional outcome was mainly reported to be good.

PMID- 14974632
TI  - Electrostimulation at sensory level improves function of the upper extremities in
      children with cerebral palsy: a pilot study.
AB  - The aim of this study was to evaluate the effect of electrical stimulation (ES)
      on the function of the upper extremities in children with cerebral palsy (CP).
      The participants were 12 children (seven females and five males) with spastic
      hemiplegia (mean age 5 years 7 months, SD 3 years 9 months). Indications were
      weak wrist dorsiflexion and elbow extension. The ES was given at sensory level
      (20-40 minutes) on the infraspinatus muscle and on the wrist dorsiflexors during
      12 regularly scheduled physical and occupational therapy sessions (during 4-5
      weeks). The Goal Attainment Scale, the Zancolli classification of hand function,
      muscle testing according to Daniels and Worthington, and King hypertonicity scale
      were used for evaluation. Assessments were made twice before (between 4 weeks)
      and twice after (between 12 weeks) the stimulation period except the King
      hypertonicity scale, which was used once before and 3 months after the
      stimulation period. Active elbow extension, wrist dorsiflexion, and forearm
      supination with the elbow flexed and extended improved when the results of
      assessments before ES were compared with those made immediately before (p<0.001)
      and three months after (p<0.01) this treatment. Results of this pilot
      uncontrolled study suggest that ES at sensory level can be used as an adjunct to
      physiotherapy and/or occupational therapy in children with spastic hemiplegia.
      These results will be used as basis for further research.

PMID- 14974633
TI  - Short-term outcome of multilevel surgical intervention in spastic diplegic
      cerebral palsy compared with the natural history.
AB  - Outcome in 24 ambulant children with spastic diplegic cerebral palsy, in whom
      multilevel surgical intervention was recommended following gait analysis, is
      reviewed. Twelve children had surgical intervention (treatment group; eight
      males, four females; mean age 9 years 10 months, SD 3 years 4 months) while the
      other 12 did not (control group; five males, seven females; mean age 10 years 1
      month, SD 2 years 11 months). All children had interval three-dimensional gait
      analyses (mean time between analyses: control group, 14.1 months; treatment
      group, 17.9 months). At follow-up the control group (mean age 11 years 9 months)
      showed a significant increase in minimum hip and knee flexion in stance which was
      not related to age, the interval between analyses, changes in the passive joint
      range of motion, nor changes in anthropometric measurements. The treatment group
      (mean age at follow-up 11 years 3 months) showed a significant improvement in
      minimum knee flexion and in ankle dorsiflexion in stance. Parents of nine
      children said their child's walking distance had increased following
      intervention. Of five children using posterior walkers preoperatively, two
      continued to use them postoperatively; two were using crutches or sticks and the
      remaining child walked independently. Two children who walked independently
      preoperatively used sticks postoperatively for community ambulation. The
      deterioration seen in the kinematics of the control group suggests that previous
      outcome studies comparing postoperative gait with preoperative gait have
      underestimated the immediate effects of surgery. It also raises concerns about
      the long-term effects of surgical intervention.

PMID- 14974634
TI  - International Classification of Functioning, Disability and Health in a cohort of
      children with cognitive, motor, and complex disabilities.
AB  - The recently endorsed World Health Organization (WHO) International
      Classification of Functioning, Disability and Health (ICF) is proposed as a new
      tool to describe human functioning and health in a multiprofessional approach for
      individuals of all ages. Its application to paediatric neurorehabilitation may be
      of great help, especially in children with complex disabilities. However,
      experience with its application in this field is still limited. We tested the
      application of ICF in 40 children (26 males, 14 females; age range 3 to 18 years;
      mean age 11 years 1 month, SD 5 years 3 months) with various types and degrees of
      disability. We tested the applicability and reliability of the classification,
      and studied its correlation with well-established measures of functioning (Verbal
      IQ; gross motor function measure; functional independence measure). The ICF
      proved to be applicable and reliable, and strongly correlated with established
      scales. However, several of the Activity and Participation components do not
      fully capture the developmental nature of many abilities of children. Our study,
      although acknowledging the universal application of the ICF, and the ICF's value
      as a clinical tool, calls for its specific adaptation to accommodate better the
      peculiarities of child functioning and disability.

PMID- 14974635
TI  - Effect of age at thyroid stimulating hormone normalization on postural control in
      children with congenital hypothyroidism.
AB  - Neonatal screening programmes allow early treatment to limit the consequences of
      congenital hypothyroidism on maturation of the central nervous system, and on
      psychomotor and educational outcome. Consequences of age at thyroid stimulating
      hormone (TSH) normalization on postural control were evaluated in 17 children
      with congenital hypothyroidism (14 females, three males; median age 12 years 1
      month, range 7 to 14 years) and in 11 control individuals (eight females, three
      males: median age 10 years 6 months, range 8 to 14 years). Children with
      congenital hypothyroidism were split into two groups according to time of TSH
      normalization: before (group 1) or after (group 2) 3 months of age. Posturography
      (static and dynamic tests), educational (school performance), and psychomotor
      (WISC and revised Bruininks Oseretsky tests) evaluations were carried out. Group
      2 results showed significant abnormalities in postural, educational, and
      psychomotor aptitudes in comparison with group 1 and control children (stability,
      Bruininks-Oseretsky, school performance: p < or = 0.05 or p < or = 0.01). Early
      TSH normalization is necessary to allow for normal development of the
      neurosensorial afferent pathways (vestibular, proprioceptive) and of central
      integration (cerebellum, vestibular nuclei).

PMID- 14974636
TI  - Effects of phototherapy on cerebral haemodynamics in preterm infants: is fibre
      optic different from conventional phototherapy?
AB  - We hypothesized that conventional phototherapy (CPT) and fibre-optic phototherapy
      (FPT) could exert different effects on cerebral blood perfusion. Our aim was to
      assess this hypothesis in a prospective study of the cerebral haemodynamics in
      preterm infants. Twenty-three infants (gestational age <34 weeks) were randomized
      for CPT (n=12) and for FPT (n=11). Cerebral Doppler ultrasounds were performed on
      all infants immediately before phototherapy (time 0), 6-12 hours (time 1) and 24
      36 hours (time 2) after the start of phototherapy, and 6-12 hours after
      discontinuing phototherapy (time 3). CPT and FPT were associated with a
      significant increase of peak-systolic blood flow velocity and mean blood flow
      velocity at time 1 and 2, which disappeared at time 3, whereas end-diastolic
      blood flow velocity and resistance index were unchanged. No difference was shown
      between the groups. CPT and FPT were found to exert similar effects on cerebral
      haemodynamics. Both were associated with an increase of cerebral blood flow
      velocity which ended when phototherapy was stopped.

PMID- 14974637
TI  - Familial cancer and developmental dyslexia: an observational pilot study.
AB  - The aim of the study was to test the hypothesis that raised platelet-activating
      factor (PAF) may contribute to the aetiology of developmental dyslexia. PAF is a
      potent proinflammatory mediator which signals cell damage and facilitates natural
      killer cell activity. Raised PAF may help protect against tumourigenesis. As
      dyslexia has a partial genetic basis, the PAF hypothesis predicts that dyslexia
      may be negatively associated with a family history of cancer. To test this
      prediction, children with dyslexia (n=163) and children without dyslexia (n=154),
      with (n=152) and without (n=165) a family history of cancer (total n=317; mean
      age 11 years 5 months, SD 2 years 11 months), were compared on standard
      psychometrics (British Ability Scales subtests). Results showed that
      proportionately fewer children with dyslexia (38%) than controls (58.4%) had a
      family history of cancer, and there was some evidence of a 'dose' effect:
      children who had more relatives with cancer showed better reading and spelling.
      It was concluded that children at genetic risk of dyslexia who have a family
      history of cancer have better reading and spelling than those without a family
      history of cancer, confirming the prediction of the PAF hypothesis.

PMID- 14974638
TI  - Variability of clinical expression and evolution of spinal deformity in a family
      with late detection of dopa-responsive dystonia.
AB  - This case report documents an unusual presentation of dopa-responsive dystonia
      (DRD) in three siblings (two females, one male) which simulated cerebral palsy
      (CP) and describes the evolution of their spinal deformity in relation to growth
      and responsiveness to levodopa therapy. The siblings were normal at birth with a
      negative history of neurological disease or spinal imbalance. They showed marked
      phenotypic variation but all developed progressive scoliosis and neurological
      impairment with mixed spastic dystonic features, leading to the misdiagnosis of
      spastic dystonic CP. Age at establishment of the diagnosis of DRD and levodopa
      trial for the three patients was 12 years, 9 years 6 months, and 3 years 6 months
      respectively. In patients 1 and 3, spinal deformity responded dramatically to
      levodopa treatment and neurological symptoms were ameliorated. Patient 2
      developed a rigid scoliotic curve and, despite neurological improvement with
      levodopa, the spinal curvature remained unresponsive necessitating surgical
      correction. Spinal decompensation is a common manifestation of DRD, which with
      early diagnosis and initiation of levodopa treatment has an excellent prognosis.
      This report highlights the variability of clinical expression in DRD and the
      importance of an adequate trial of levodopa when unexplained dystonic features
      are documented.

PMID- 14974639
TI  - Natural history of obstetric brachial plexus palsy: a systematic review.

PMID- 14974640
TI  - Plus ca change?

PMID- 14974641
TI  - Outcome after prolonged convulsive seizures in 186 children: low morbidity, no
      mortality.
AB  - Prolonged convulsive seizures are a common neurological emergency and a potential
      cause of neuronal damage and functional sequelae. We explored the role of seizure
      duration and various background factors for neurological sequelae in children
      with prolonged convulsive seizures. The population-base of this study was all
      children (age < 16 years) who had been admitted to the Tampere University
      Hospital, Finland between 1993 and 1999 with convulsive seizures lasting more
      than 5 minutes. Patients were followed up individually (mean length of follow-up
      2 years 1 month, range 0 to 7 years 8 months). All available data on the
      prolonged seizure episodes and clinical follow-up were analyzed retrospectively
      by a detailed review of all medical charts and records. In 186 children (94
      males, 92 females; mean age 4 years 5 months, SD 3 years 10 months, range 1 month
      to 15 years 4 months) there were 279 separate convulsive seizure episodes lasting
      over 5 minutes, yielding an annual incidence of 47.5 out of every 100000
      episodes. Seizure aetiology was idiopathic in 26.2% of episodes, febrile in
      41.9%, remote symptomatic in 28%, and acute symptomatic in 3.9% of episodes. Mean
      duration of all seizure episodes was 42.5 minutes (SD 46.1 minutes) and was
      significantly correlated with the aetiology: shortest in the febrile group (mean
      35.4 minutes) and longest in the acute symptomatic group (mean 88.6 minutes; p <
      0.001). There was no mortality related directly to these acute seizure episodes.
      The most common sequela was an onset of epilepsy in 40 children (22%). Permanent
      neurological sequelae were noted in only four patients (2.2%; mean seizure
      duration 16 minutes) and non-permanent sequelae in six patients (3.2%; mean
      seizure duration 38 minutes). Neurological sequelae of prolonged convulsive
      seizures in children are rare and are related to aetiological factors rather than
      the duration of a single seizure. The role of acute seizures in the evolution of
      epilepsy in children remains obscure.

PMID- 14974642
TI  - Clinical validation of the paediatric pain profile.
AB  - The Paediatric Pain Profile (PPP) is a 20-item behaviour rating scale designed to
      assess pain in children with severe neurological disability. We assessed the
      validity and reliability of the scale in 140 children (76 females, mean age 9
      years 11 months, SD 4 years 7 months; range 1 to 18 years), unable to communicate
      through speech or augmentative communication. Parents used the PPP to rate
      retrospectively their child's behaviour when 'at their best' and when in pain. To
      assess interrater reliability, two raters concurrently observed and individually
      rated each child's behaviour. To assess construct validity and responsiveness of
      the scale, behaviour of 41 children was rated before and for four hours after
      administration of an 'as required' analgesic. Behaviour of 30 children was rated
      before surgery and for five days after. Children had significantly higher scores
      when reported to have pain than 'at their best' and scores increased in line with
      global evaluations of pain. Internal consistency ranged from 0.75 to 0.89
      (Cronbach's alpha) and interrater reliability from 0.74 to 0.89 (intraclass
      correlation). Sensitivity (1.00) and specificity (0.91) were optimized at a cut
      off of 14/60. PPP score was significantly greater before administration of the
      analgesic than after (paired-sample t-tests, p<0.001). Though there was no
      significant difference in mean pre- and postoperative scores, highest PPP score
      occurred in the first 24 hours after surgery in 14 (47%) children. Results
      suggest that the PPP is reliable and valid and has potential for use both
      clinically and in intervention research.

PMID- 14974643
TI  - Disturbances in programming goal-directed arm movements in children with ADHD.
AB  - We investigated in children with attention-deficit-hyperactivity disorder (ADHD)
      the ability to programme and execute goal-directed arm movements. The sample
      consisted of 25 males with ADHD (mean age 11 years 6 months, SD 1 year 11 months,
      range 8 to 15 years) and 25 age-matched typically developing males. The children
      moved a cursor on a screen by moving a hand-held indicator on a horizontal
      digitizing tablet. Start and target positions on the screen were always visible
      during the movement. The screen cursor, however, could either be visible
      throughout the movement (visual feedback) or blanked at movement initiation
      (without visual feedback). Analysis showed that movement control was impaired in
      children with ADHD and that their problems were especially pronounced during the
      without-visual-feedback condition. In this condition, the children with ADHD
      exhibited large end-point errors and prolonged movement durations. As there can
      be no visual corrections of the movement during this condition, results indicate
      poorer motor programming in children with ADHD. Moreover, children with ADHD
      performed jerky movements and showed a reduced capacity to select a movement
      speed that met with the accuracy demands of the movement.

PMID- 14974644
TI  - Control of reaching movements in children and young adults with myelomeningocele.
AB  - The aim of the present study was to analyze the ability to programme and execute
      reaching movements in individuals with myelomeningocele (MMC) and in a control
      group. Thirty-one participants (18 males, 13 females; mean age 12 years 11
      months, SD 2 years 7 months, range 9 to 19 years) with MMC and 31 participants
      (matched for age and sex) without disabilities were investigated. Reaching was
      performed with and without visual feedback toward three targets displayed on a
      computer screen and data were collected using a digitizing tablet linked to a
      computer. The kinematics of reaching were analyzed and analysis of variance was
      used for statistical analysis. Results showed that both groups were able to
      programme reaching movements under both visual conditions. Although the execution
      of reaching was poor in the MMC group compared with the control individuals, as
      indicated by larger end-point errors (p=0.002), less straight movements
      (p=0.018), and shorter deceleration phases (p=0.004), movement time was not
      prolonged in the MMC group. Those with shunt treatment (n=21) had more
      difficulties when visual feedback was provided. Those with symptoms of early
      brainstem dysfunction (n=5) had shorter deceleration phases under both visual
      conditions.

PMID- 14974645
TI  - Energy cost of walking in children with cerebral palsy: relation to the Gross
      Motor Function Classification System.
AB  - This study compared the energy cost of walking in children with cerebral palsy
      (CP) classified at different levels of the Gross Motor Function Classification
      System (GMFCS) with that in children with typical development. Sixteen female and
      14 male children with CP (mean age 9 years 6 months, SD 2 years 4 months, range 6
      years 4 months to 13 years 4 months) and 14 male and 13 female typically
      developing children (mean age 10 years, SD 1 year 6 months, range 7 years 1 month
      to 12 years 11 months) participated. Children with CP were classified at GMFCS
      level I, n=5; level II, n=10; level II, n=9; and level IV, n=6. Energy cost was
      assessed by the gas dilution method as each child walked around an oval track
      wearing a dilution mask. Significant differences were found across GMFCS levels
      (p<0.0001) and between adjacent levels (p<0.013). Children with CP displayed a
      higher energy cost of walking than the typically developing children (p<0.0001).
      A strong correlation (0.87) was found between the energy cost of walking and
      GMFCS level (p<0.01) when children with typical development were assigned a GMFCS
      level of zero to allow statistical analysis. This indicates increasing energy
      cost of walking with increasing severity of functional involvement. These
      differences in energy cost across GMFCS levels provide another distinguishing
      factor between GMFCS levels and further emphasize the importance of considering
      metabolic demand in determining treatment options.

PMID- 14974646
TI  - Effectiveness of the Innsbruck Sensorimotor Activator and Regulator in improving
      saliva control in children with cerebral palsy.
AB  - The aim of this study was to determine the effectiveness of an intraoral
      appliance, the Innsbruck Sensorimotor Activator and Regulator (ISMAR), in
      improving drooling and eating skills in a group of children with cerebral palsy,
      and to determine which factors might indicate good candidates for this type of
      treatment. Eighteen children (13 males, five females; mean age 7 years 10 months,
      range 4 to 13 years) were selected. Measures of drooling and feeding skills were
      taken at baseline, at the completion of a 6-month control phase, and at two more
      6-monthly time points after the ISMAR was fitted. Children varied greatly in both
      the length of time taken to tolerate wearing the ISMAR and duration for which the
      appliance was worn. Only six children (four females, two males) completed the
      full study. Their motor disabilities were athetosis (n=3), spastic quadriplegia
      (n=2), and hypotonia (n=1); four of the six children used a wheelchair for
      locomotion. None had epilepsy and none had greater than mild cognitive
      impairment. For these children drooling severity scores and eating and drinking
      skills improved significantly over the treatment period in comparison with the
      control phase. We conclude that the ISMAR remains a valid option in improving
      drooling in children and merits further study.

PMID- 14974647
TI  - Effects of very low birthweight on brain structure in adulthood.
AB  - Very-low-birthweight (VLBW) individuals are at high risk of brain injury in the
      perinatal period. We wished to determine how such early brain lesions affect
      brain structure in adulthood. Thirty-two VLBW adults (20 female, 12 male) and 18
      term, normal birthweight sibling control individuals (nine female, nine male)
      underwent structural MRI at a mean age of 23 years 4 months (range 17 to 33
      years; SD 3.4). Images were analyzed using an automated tissue segmentation
      algorithm in order to estimate whole brain tissue class volumes in native space.
      Images were then warped to a template image in standard space. There was no
      significant between-group difference in whole brain, grey matter, white matter,
      or total cerebral spinal fluid (CSF) volumes. However, lateral ventricular volume
      was significantly increased by 41% in those with VLBW. The ratio of grey to white
      matter was also significantly increased (by 10%) in those with VLBW. Group
      comparison maps showed widespread changes in the distribution of grey and white
      matter, and relative excess of ventricular CSF, in the brains of VLBW
      individuals. Increased ventricular volume predicted decreased grey matter in
      subcortical nuclei and limbic cortical structures, and decreased periventricular
      white matter. We conclude that these diffuse abnormalities of grey and white
      matter are a consequence of the interaction of perinatal brain injury and ongoing
      neurodevelopmental processes.

PMID- 14974648
TI  - Congenital trigeminal anaesthesia.
AB  - Two patients with congenital trigeminal nerve anaesthesia are described. The
      first (male, aged 14 years) had an isolated unilateral loss of sensation in all
      three divisions of the trigeminal nerve with no other abnormalities. The second
      patient (male, aged 3 years 6 months) had bilateral loss of sensation in all
      three divisions of the trigeminal nerve, associated with other neurological
      abnormalities. No explanation for their abnormalities was found. The Rosenberg
      classification of congenital trigeminal anaesthesia is discussed with reference
      to these patients and also with reference to the developmental biology of the
      trigeminal nerve.

PMID- 14974649
TI  - Patient with partial trisomy 9q and learning disability but no pyloric stenosis.
AB  - Partial trisomy of the long arm of chromosome 9 represents a very rare and
      heterogeneous group of chromosomal aberrations. Associated clinical features
      include learning disability and pyloric stenosis. We present the first patient to
      be reported with a duplication of the chromosome region 9q22.1-->q33. The patient
      (female, age 17 years) presented with growth retardation, microcephaly, facial
      dysmorphia, oesophageal atresia, aortic stenosis, ventricular septal defect,
      atrial septal defect II, hypothyroidism, and learning disability, but no pyloric
      stenosis. A review of all cases of partial trisomy 9q reported in the literature
      demonstrates that learning disability is a characteristic feature of this group
      of chromosomal aberrations. However, there are cases of duplications of the same
      chromosome 9 material, with and without pyloric stenosis. This study provides new
      information for future genetic counselling, especially in cases of prenatal
      diagnosis of partial trisomy 9q.

PMID- 14974650
TI  - Gross Motor Function Classification System: impact and utility.
AB  - In summary, the GMFCS has had, and continues to have, a major effect on the
      health care of children with CP. The number of citations of the GMFCS has been
      increasing every year, and the classification system has had good uptake
      internationally and across the spectrum of health professionals for use in
      research design and clinical practice by providing a system for clearly
      communicating about children's gross motor function. The utility of diagnostic
      labels such as diplegia has been questioned. However, although by definition CP
      is a disorder of posture and movement, the movement disability is often only one
      of the neurodevelopmental problems for many children with CP. When a complete
      description of a child's clinical presentation is required we recommend that the
      GMFCS be used together with the Surveillance of Cerebral Palsy in Europe
      classification indicating the type and topography of movement impairment. When
      appropriate the clinical profile will similarly be enhanced with details of other
      impairments and disabilities such as epilepsy or sensory, learning, feeding, or
      emotional disturbance. The observations in this annotation are constrained by the
      amount of information in the public domain. Although these sources adequately
      represent the effect of the GMFCS on research design, they are less likely to
      inform us of how the GMFCS is being used in administration, clinical practice, or
      education. It is not yet clear whether information is being used for these
      purposes or in assisting with case load management, as intended by the
      developers. By its localized nature, such information might remain difficult to
      gauge. We would therefore be interested to hear from others who are using the
      system for these or any other purposes.

PMID- 14974651
TI  - Visual impairment in children with brain damage: towards a diagnostic procedure?

PMID- 14974652
TI  - Developing Mac Keith "college".

PMID- 14974653
TI  - The US medical liability system--a system in crisis.

PMID- 14974654
TI  - Laparoscopic ureteroneocystostomy and vesicopsoas hitch for infiltrative
      endometriosis.
AB  - OBJECTIVE: To report a series of laparoscopic vesicopsoas hitch procedures
      performed for the treatment of infiltrative ureteral endometriosis. METHODS: A
      retrospective chart review of 6 women with severe endometriosis and ureteral
      obstruction caused by infiltrative disease of the distal ureter was performed.
      The patients underwent successful laparoscopic ureteroneocystostomy and
      vesicopsoas hitch. RESULTS: Five of the 6 patients had a history of
      endometriosis, and their obstructions were diagnosed during prior surgeries. The
      other patient was diagnosed with severe endometriosis of the rectum, bladder, and
      ureter at the time of the procedure. She was referred for evaluation of an
      incidental finding of hydroureter and hydronephrosis. Three patients were treated
      with gonadotrophin-releasing hormone (GnRH) analog for at least 3 months
      preoperatively. Five patients had ureteral stents in place prior to the psoas
      hitch surgery. No intra- or postoperative complications occurred. All patients
      had a normal cystogram performed 10 to 14 days postoperatively prior to Foley
      catheter removal. Stents were kept in place for 6 to 8 weeks, and an intravenous
      pyelogram (IVP) was done 2 weeks after removal. All patients had a normal renal
      ultrasound, computer tomography, or intravenous pyelogram at least 1 year
      postoperatively. CONCLUSION: Laparoscopic vesicopsoas hitch can be a safe and
      effective alternative to the laparotomy with the known benefits of laparoscopy.

PMID- 14974655
TI  - Octylcyanoacrylate skin closure in laparoscopy.
AB  - OBJECTIVES: Octylcyanoacrylate (Dermabond) is a dermal bond useful in closing
      surgical skin incisions. We compared skin octylcyanoacrylate with subcuticular
      skin sutures to close laparoscopic trocar sites. METHODS: A randomized, double
      armed, prospective study was performed with 59 patients, in whom 228 trocar sites
      were closed. Twenty-nine patients underwent subcuticular closure of laparoscopic
      incisions, and 30 patients received closure with octylcyanoacrylate. Sutured
      trocar sites were closed with subcuticular 4-0 absorable suture.
      Octylcyanoacrylate wounds received closure in accordance with the recommendations
      of the manufacturer (Ethicon, Somerville, NJ). The number of sutures or vials of
      octylcyanoacrylate used, closure times, and postoperative wound problems were
      recorded. Wounds were assessed 2 weeks postoperatively for healing complications.
      Closure costs were estimated using published operating room time per hour plus
      the cost of octylcyanoacrylate or suture. The Student paired t test was used for
      statistical analysis. RESULTS: The overall mean time for skin closure using
      octylcyanoacrylate and suture was 3.7 minutes and 14 minutes, respectively
      (P<0.00001). An average of 2.2 packets of suture were used to close all port
      sites, while those closed with octylcyanoacrylate required an average of 3.4
      vials per patient. Wound complications consisted of subcuticular seroma with skin
      separation. No difference was noted in complication rates between the 2 groups.
      Overall average cost per closure using octylcyanoacrylate was 198 dollars while
      cost for closure using suture was 497 dollars (P<0.00001). CONCLUSIONS:
      Laparoscopic port-site skin closure with octylcyanoacrylate is rapid and
      effective. Closure with octylcyanoacrylate yields cost savings and a decrease in
      operative time of more than 9 minutes per case.

PMID- 14974656
TI  - Preemptive analgesia does not reduce pain or improve postoperative functioning.
AB  - OBJECTIVES: To examine the effectiveness of preemptive analgesia in gynecologic
      laparoscopy patients. METHODS: A double-blinded, randomized trial was performed
      from June 2000 to June 2001. Preoperatively, patients were randomly assigned to
      0.25% bupivicaine or normal saline control. Following anesthetic induction, the
      study drug or a placebo was injected prior to the proposed incisions. RESULTS: Of
      the 164 patients enrolled, 85 were randomized to the study group and 79 to the
      control. Age, surgery indication, and estimated blood loss did not vary
      significantly between groups. Overall mean pain score (+/-standard error of the
      mean) for study and control groups did not differ at 4 hours (3.2+/-0.3 vs 3.2+/
      0.3) or at 24 hours (4.2+/-0.3 vs 4.2+/-0.3). Incisional pain scores also did not
      differ at 4 hours (3.0+/-0.3 vs 2.7+/-0.3) or at 24 hours (3.6+/-0.3 vs 3.6+/
      0.3). Both groups were similar in activity limitation at 24 hours and oral
      narcotic consumption within 24 hours postoperatively. After stratifying surgery
      type for level of complexity, no difference was noted between groups. Multiple
      logistic regression analysis also noted no difference in outcomes. CONCLUSION:
      Preemptive analgesia in patients undergoing gynecologic laparoscopy does not
      reduce postoperative pain or decrease the time to return of normal activities.

PMID- 14974657
TI  - Laparoscopic Roux-en-Y gastric bypass for recalcitrant gastroesophageal reflux
      disease in morbidly obese patients.
AB  - BACKGROUND AND OBJECTIVES: Gastroesophageal reflux disease (GERD) is commonly
      associated with morbid obesity (MO). Antireflux surgery has a higher failure rate
      in MO and addresses only one of the comorbidities present. This paper reviews the
      results of laparoscopic Roux-en-Y gastric bypass (LRYGBP) performed for
      recalcitrant GERD in MO. METHODS: Patients with recalcitrant GERD and a body mass
      index (BMI)>35 undergoing LRYGBP were included. LRYGB included crural repair,
      creation of a small gastric pouch (30 mL), and intestinal bypass (150 to 180 cm).
      All patients were followed in clinic and by telephone. RESULTS: From February
      1999 to April 2001, 57 patients (51 F, 6 M) with a mean age of 43 (range, 22 to
      67) and a median BMI of 43 underwent LRYGBP. Hiatal hernia or esophagitis, or
      both, were present in 48, Barrett's in 2. LRYGBP was possible in 52 patients; 5
      required open conversion. The median hospital stay was 3 days. Complications
      included 1 leak, 1 pulmonary emboli, 2 reoperations for internal roux limb
      hernia, and 7 gastrojejunal strictures. At a mean follow-up of 18 months (range,
      3 to 30), all patients report improvement or no symptoms of GERD and a mean
      weight loss of 40 kg (range, 16 to 70). Quality of life scores (SF-36) were above
      national norms for physical and mental components (median 55, norms=50). GERD
      health related quality of life median score was <1 (scale, 0 to 45,
      0=asymptomatic, 45=worse). CONCLUSION: LRYGBP was effective for recalcitrant GERD
      in MO. LRYGBP also led to weight loss and improvement in other comorbidites.
      Surgeons with minimally invasive expertise should consider LRYGBP for treatment
      of GERD in the morbidly obese.

PMID- 14974658
TI  - The laparoscopic approach in abdominal emergencies: a single-center 10-year
      experience.
AB  - INTRODUCTION: Laparoscopy has rapidly emerged as the preferred surgical approach
      to a number of different diseases because it allows for a correct diagnosis and
      proper treatment. In abdominal emergencies, both components of treatment-
      exploration and surgery--can be accomplished via laparoscopy. The aim of the
      present work is to illustrate retrospectively the results of a case-control
      experience with laparoscopic versus open surgery for abdominal emergencies
      performed at our institution. METHODS: From January 1992 to January 2002, 935
      patients (mean age, 42.3+/-17.2 years) underwent emergent or urgent surgery, or
      both. Of these, 602 (64.3%) were operated on laparoscopically (small bowel
      obstruction, 28; gastroduodenal ulcer disease, 25; biliary disease, 165; pelvic
      disease, 370 cases; colonic perforations, 14) based on the availability of a
      surgical team trained in laparoscopy. Patients with a history of malignancy, more
      than 2 previous major abdominal surgeries, or massive bowel distension were not
      treated laparoscopically. Peritonitis was not deemed a contraindication to
      laparoscopy. RESULTS: The conversion rate was 5.8% and was mainly due to the
      presence of dense intraabdominal adhesions. Major complications ranged as high as
      2.1% with a postoperative mortality of 0.6%. A definitive diagnosis was
      accomplished in 96.3% of cases, and 94.1% of these patients were treated
      successfully with laparoscopy. CONCLUSIONS: Even if limited by its retrospective
      nature, the present experience shows that the laparoscopic approach to abdominal
      emergencies is as safe and effective as conventional surgery, has a higher
      diagnostic yield, and results in less trauma and a more rapid postoperative
      recovery. Such features make laparoscopy an attractive alternative to open
      surgery in the management algorithm for abdominal emergencies.

PMID- 14974659
TI  - Pediatric empyema--an algorithm for early thoracoscopic intervention.
AB  - INTRODUCTION: The management of pediatric empyema remains controversial. We
      contend that early thoracoscopic intervention results in shorter hospital stays,
      decreased morbidity, and superior outcomes. We propose an algorithm using early
      image-guided thoracoscopy as an effective treatment for pediatric empyema.
      METHODS: Consecutive pediatric empyemas treated from November 1997 to April 2001
      using a prospective management algorithm were reviewed. Demographic data, days to
      diagnosis, days to surgery, length of stay, chest tube days, complications, and
      follow-up were recorded. RESULTS: Twenty-two children with 24 empyemas were
      treated using this algorithm. Their mean age was 49 months. Mean days to
      diagnosis was 11 and from diagnosis to surgery was 3. Imaging included chest
      radiography (CXR) in all, ultrasound in 17 (77%), and computed tomography (CT)
      scan in 13 (59%). One thoracoscopy was converted to a mini-thoracotomy because of
      difficulty with ventilation. Chest tube removal averaged 3 days with an average
      length of stay of 13 days. One patient required a second thoracoscopy for
      recurrent empyema, and 1 patient developed a contralateral empyema. No other
      complications or deaths occurred. Follow-up in 19 of 22 (86%) children at 5
      months revealed no recurrences or mortality. CONCLUSION: This treatment
      algorithm, using early image-guided thoracoscopy, is a safe and effective means
      of managing pediatric empyema, while shortening hospital stay and avoiding the
      morbidity of thoracotomy.

PMID- 14974660
TI  - Video-assisted thoracoscopic suture closure of blebs to treat primary spontaneous
      pneumothorax.
AB  - BACKGROUND AND OBJECTIVES: If surgery is indicated for primary spontaneous
      pneumothorax (PSP), video-assisted thoracoscopic surgery (VATS) using an
      endoscopic linear cutter to resect the involved blebs is the most popular
      treatment. We tried to determine whether closure of the blebs with sutures
      without resection is also efficacious enough to treat PSP. METHODS: We
      prospectively analyzed 22 episodes of PSP in 21 patients from January 2001 to
      April 2002. We endosutured the blebs, without removing them, no matter what the
      size and the number of the blebs were. Coagulation pleurodesis was added in every
      case. Only 3 ports were needed during the procedure. RESULTS: Morbidity and cost
      efficiency were acceptable. Two recurrences were experienced. The reasons for the
      recurrences were poor performance of the endo-suture in 1 patient, and no obvious
      blebs found in the other. CONCLUSIONS: We believe that VATS wedge closure of
      blebs by imbricating and buttressing them, without resection, is a feasible and
      effective alternative treatment for primary spontaneous pneumothorax.

PMID- 14974661
TI  - Impalpable testis and laparoscopy: when the gonad is not visualized.
AB  - The diagnostic accuracy of laparoscopy for impalpable testis is well recognized.
      However, in some cases, laparoscopic findings may be misleading, and a viable
      gonad may be missed with significant medico-legal implications. From January 1993
      to December 2000, 202 patients with 219 impalpable testes were evaluated. In 95
      cases, the gonad was immediately visualized, and in 5, the presence of a testis
      was documented by inserting the scope into the processus vaginalis. In the 119
      remaining cases, no gonad was seen while entering the abdomen with the
      laparoscope. All patients with documented vas and vessels exiting the inguinal
      ring were surgically explored. Ten testes were found, 8 ectopic, with significant
      changes in shape and position, and 2 were canalicular. In the absence of hormone
      stimulation, no testes were found while exploring patients with cord structures
      coursing a closed inguinal ring and with contralateral hypertrophy. In 1 patient
      with absent vas and vessels, the testis was found at the lower renal pole while
      removing a dysplastic kidney. Despite technical refinements and an increase in
      clinical practice, a small percentage of viable testes may be missed with
      laparoscopic findings consistent with absent/vanished inguinal testis. Therefore,
      inguinal exploration is mandatory in all these cases.

PMID- 14974662
TI  - The role of laparoscopy in the localization and management of adult impalpable
      testes.
AB  - BACKGROUND: Very few studies are available that describe the role of laparoscopy
      in adults with impalpable testes. This study compares laparoscopy with
      ultrasonography in this subset of patients. METHODS: Fourteen adults, having a
      mean age of 21 years, with 19 undescended testes were evaluated. None of the
      testes was palpable, preoperative ultrasound localized 7 testes (36.8%), but a
      change in findings was observed in 3 of these cases (42.8%) on subsequent
      laparoscopy. On laparoscopy, 18 (94.7%) of the testes were localized as
      intraabdominal. The remaining patient had a case of true anorchia. Seven patients
      with unilateral undescended testes underwent laparoscopic orchiectomy, and 2
      patients with unilateral undescended testes and all the patients with bilateral
      undescended testes underwent laparoscopic-assisted orchiopexy. No complication
      was noted in any of the cases. Hernia, present in 4 patients, was simultaneously
      repaired laparoscopically. CONCLUSION: Laparoscopy is a safe and effective
      modality in the localization and management of adult undescended testes. In
      adults, orchiectomy with the subsequent reduction in the risk of malignancy is
      the major issue of concern. Also, the repair of concomitant hernias is desirable.
      Both of these procedures can be done laparoscopically in the same sitting without
      the need for inguinal exploration.

PMID- 14974663
TI  - The use of blunt-tipped 12-mm trocars without fascial closure in laparoscopic
      live donor nephrectomy.
AB  - OBJECTIVES: Blunt-tipped trocar placement may eliminate the need for fascial
      closure in transperitoneal laparoscopic live donor nephrectomies (LDN). The
      process of 12-mm blunt-tipped trocar insertion through the abdominal wall
      involves fascial and muscle spreading, not incision. Coaptation of the tissue
      layers occurs during withdrawal of the trocar, preventing volume gaps that can be
      prone to herniation. METHODS: We retrospectively assessed the safety and efficacy
      of fascial nonclosure after 12-mm blunt-tipped port insertion in 70
      transperitoneal LDNs performed between October 1998 and March 2001. Five ports
      (two 12-mm blunt-tipped and three 5-mm blunt-tipped) were used in all cases. The
      12-mm trocars were inserted at the lateral border of the rectus muscle,
      approximately 8 cm below the costal margin and also along the anterior axillary
      line approximately 8 cm below the costal margin. Fascial non-closure was
      performed in all 70 patients. Postoperative data were analyzed regarding
      complications and long-term outcomes. RESULTS: Three major and 7 minor
      complications occurred in this series. No patient developed clinically detectable
      trocar-site hernias or other complications related to blunt-trocar placement.
      CONCLUSIONS: Our data shows that fascial nonclosure after transperitoneal 12-mm
      blunt-tipped trocar insertion is safe. Visualization of the tissue layers during
      port placement facilitated the insertion process. Further application of this
      method in a larger number of patients is needed to confirm its clinical
      applicability.

PMID- 14974664
TI  - Laparoscopic partial nephrectomy using holmium laser in a porcine model.
AB  - OBJECTIVE: To evaluate the utility of the holmium laser for partial nephrectomy
      in a porcine model. METHODS: Transperitoneal lower pole laparoscopic partial
      nephrectomy was performed in 5 farm pigs. All animals underwent a left-sided
      laparoscopic partial nephrectomy and were kept alive for 2 weeks (survival
      group). Subsequently, a right laparoscopic partial nephrectomy was performed
      (acute group), and the animals were sacrificed. A 1000-microm (n=6) or 550-microm
      (n=4) end-fire holmium laser fiber set at 0.2 joules and 60 pulses per second was
      used to transect the lower pole of the kidney 1 cm below the level of the hilum.
      The cut parenchymal surface was then sealed with fibrin glue in the survival
      animals. The operated on kidneys were inspected grossly and evaluated
      microscopically. RESULTS: Laser transection was successfully completed in all
      cases, and hemostasis proved adequate without any adjunctive measures. No
      perioperative complications occurred. Estimated blood loss was less than 50 cc
      for each laparoscopic partial nephrectomy. The acute and survival pigs showed no
      statistically significant differences in specimen size or weight. Serum
      creatinine levels were normal in all survival animals. Extravasation was noted on
      retrograde pyelograms of 2 animals in the survival group. CONCLUSIONS: The
      Holmium:YAG laser provides an efficacious modality for transecting the kidney in
      a porcine model. Clinical trials are necessary to determine its role in
      laparoscopic partial nephrectomy in humans.

PMID- 14974665
TI  - Operative laparoscopy in pregnancy.
AB  - OBJECTIVE: We compared the surgical outcomes of pregnant women undergoing
      laparotomy in the first 2 trimesters of pregnancy with those undergoing
      laparoscopy for the management of acute pelvic pain. METHODS: We performed a
      systematic retrospective chart review of patients whose discharge diagnosis
      included intrauterine pregnancy with exploratory laparotomy or laparoscopy from
      August 1, 1993 to October 31, 1999. The following factors were assessed:
      preoperative diagnosis, postoperative diagnosis, gestational age at the time of
      surgery, operative time, hospital stay, pathology, gestational age at delivery,
      complications, and outcome of the pregnancy in both groups. RESULTS: Sixteen
      pregnant patients underwent surgery during the study period. All but one had
      abdominopelvic pain, and all patients had an associated adnexal mass. The mean
      gestation age at the time of surgery was 15+/-6 weeks versus 13+/-4 weeks in the
      laparoscopic and laparotomy groups, respectively (P=NS). All patients undergoing
      laparoscopy remained in the hospital for one day compared with a mean of 4.4+/
      1.1 days in the laparotomy group (P<0.0001). Pregnancy outcomes were similar and
      uniformly good. CONCLUSION: Laparotomy can be avoided and pregnant patients
      managed safely by operative laparoscopy, with shorter hospital stays.

PMID- 14974666
TI  - Acute cholecystitis and severe ischemic cardiac disease: is laparoscopy
      indicated?
AB  - BACKGROUND AND OBJECTIVES: Laparoscopy in patients with poor cardiac function has
      been the subject of controversy and is considered by many surgeons a relative
      contraindication. METHODS: We report the case of a patient who presented with
      acute cholecystitis and choledocholithiasis concurrent with unstable angina. Our
      experience in laparoscopic management of patients with calculous biliary disease
      and severe coronary artery disease is examined. RESULTS: The patient was managed
      by coronary angioplasty and stenting immediately followed by laparoscopic
      cholecystectomy and common bile duct exploration under close invasive hemodynamic
      monitoring and low-pressure pneumoperitoneum. Between 1996 and 2001, 39 patients
      with coronary artery disease and an ASA class of III or IV underwent laparoscopic
      cholecystectomy. Eight of these patients (20.5%) had common bile duct stones
      necessitating laparoscopic common bile duct exploration. No conversions were
      necessary, and no major morbidity or mortalities occurred. CONCLUSIONS:
      Laparoscopic cholecystectomy and common bile duct exploration can be safely
      performed in patients with severe ischemic cardiac disease under close
      hemodynamic monitoring and a low-pressure pneumoperitoneum (10 to 12 mm Hg).

PMID- 14974667
TI  - Recurrent asystolic cardiac arrest and laparoscopic cholecystectomy: a case
      report and review of the literature.
AB  - Laparoscopic surgery has become a durable alternative for both gynecologic and
      general surgical procedures, but reported complications are increasing. We
      describe the case of a 70-year-old male undergoing routine laparoscopic
      cholecystectomy for gallstone pancreatitis who developed asystolic cardiac arrest
      intraoperatively. A review of the literature revealed 2 cases of asystolic
      cardiac arrest during laparoscopy: one was during laparoscopic cholecystectomy
      and one was during diagnostic laparoscopy for gynecologic evaluation.

PMID- 14974668
TI  - Hand-assisted laparoscopic splenectomy: indications and technique.
AB  - INTRODUCTION: Laparoscopic splenectomy has become the procedure of choice for
      those patients who need to have a splenectomy. The skills required to perform a
      laparoscopic splenectomy are not easy to learn and therefore may limit the
      availability of this procedure to patients. METHODS: We present a hand-assisted
      technique that allows the performance of a laparoscopic splenectomy safely and
      rapidly by surgeons without a great deal of experience with this procedure.
      RESULTS: A laparoscopic hand-assisted splenectomy was performed by a chief
      resident who had not performed this procedure before. The operative time was
      comparable to that of a laparoscopic splenectomy performed by an experienced
      laparoscopic surgeon at our institution (65 vs 62 min). CONCLUSIONS: The hand
      assisted technique is useful in a number of laparoscopic situations. We suggest
      that hand-assisted laparoscopic surgery might be used as an adjunct for surgeons
      with limited laparoscopic experience and for residents who are learning advanced
      laparoscopic skills.

PMID- 14974669
TI  - Biliary stent causing colovaginal fistula: case report.
AB  - OBJECTIVES: Perforation of the bowel during placement of a biliary stent is a
      known complication of this procedure. We report the endoluminal loss of a biliary
      stent during routine stent extraction that ultimately led to a chronic
      colovaginal fistula. This case emphasizes the need for evaluation of fecal
      passage of stents in patients with a known dislodged prosthesis. CASE REPORT: A
      65-year-old white female underwent biliary stent placement for an episode of
      choledocholithiasis. The stent was lost in the duodenum during routine
      extraction. The patient was managed expectantly. She denied ever passing this
      stent via the rectum and began to develop symptoms of colovaginal fistula.
      Evaluation found a retained biliary stent in the sigmoid colon and a fistula into
      the vagina. The patient underwent elective low anterior resection and colovaginal
      fistula repair. DISCUSSION: Reports exist of migration of stents that lead to
      acute colonic perforation and the need for emergent surgery. For this reason, it
      has been suggested that dropped or migrated stents be purposefully retrieved.
      However, if the option of expectant observation is used, it is important to
      clearly document the fecal passage of these stents and be prepared to retrieve
      these objects if they have a prolonged bowel transit time.

PMID- 14974670
TI  - Laparoscopic wedge resection of gastric leiomyoma.
AB  - Gastric leiomyoma is a relatively rare gastric neoplasm. Before the routine use
      of laparoscopy, various methods of treatment for gastric leiomyoma included open
      celiotomy with gastric wedge resection, partial gastrectomy, enucleation, and
      extended gastrectomy with en bloc resection of adjacent organs. Below, we
      describe a case of laparoscopic wedge resection and review the various
      laparoscopic techniques for the treatment of gastric leiomyoma.

PMID- 14974671
TI  - External iliac vein injury and its repair during laparoscopic radical cystectomy.
AB  - We describe a case of external iliac vein injury, sustained during laparoscopic
      radical cystectomy, which was managed laparoscopically with intracorporeal
      suturing.

PMID- 14974672
TI  - Sporadic gastric carcinoid tumor laparoscopically resected: a case report.
AB  - Sporadic gastric carcinoid tumors are relatively infrequent malignancies of the
      stomach. Tumors measuring less than 1 cm can sometimes be safely removed
      endoscopically; however, larger neoplasias require surgical ablation. The present
      case report represents a gastric carcinoid tumor laparoscopically resected in a
      patient with a history of hematemesis. The tumor was first marked endoscopically
      with India ink, which facilitated subsequent localization of the area to be
      resected. Laparoscopic resection of the mass was without complication, and the
      pathology study confirmed the preoperative diagnosis and negativity of the
      margins. In patients who present with masses that are not amended for endoscopic
      resection, sporadic gastric carcinoid tumors can be resected laparoscopically.

PMID- 14974673
TI  - Intestinal obstruction after totally extraperitoneal laparoscopic inguinal hernia
      repair.
AB  - Laparoscopic hernia repair is a frequently performed operation. Although it has
      many advantages over open inguinal hernia repair, laparoscopic surgery is not
      without complications. Small bowel obstruction is a complication unique to
      laparoscopic repair of inguinal hernias. It is reported following transabdominal
      preperitoneal repairs. We present a case of small bowel incarceration through a
      peritoneal defect after a totally extraperitoneal inguinal hernia repair.
      Techniques to avoid this complication are presented. The literature is reviewed.

PMID- 14974674
TI  - Laparoscopic management of traumatic hemorrhagic cholecystitis.
AB  - BACKGROUND AND OBJECTIVES: Blunt trauma to the gallbladder is a rare entity,
      particularly when no other organ is injured. In isolated blunt traumatic injury
      to the gallbladder, treatment options vary depending on the specific injury. The
      types of blunt trauma injuries to the gallbladder and their appropriate
      management are discussed. In addition, a case successfully managed with minimally
      invasive techniques is presented. METHODS: A passenger admitted after a high
      speed front-end motor vehicle crash was safely managed with laparoscopic surgery
      for a rare case of isolated gallbladder trauma. The preoperative and operative
      management are discussed as well as the application of minimally invasive surgery
      for this rare process. RESULTS: Laparoscopic cholecystectomy was performed
      successfully. The patient did well postoperatively with no complications. No
      other injuries were identified at the time of laparoscopy. CONCLUSION: Minimally
      invasive techniques may be safely applied to blunt trauma of the gallbladder in
      certain circumstances.

PMID- 14974675
TI  - Profile of Ralph Victor Clayman, MD, professor and Chair, Department of Urology,
      University of California Irvine.

PMID- 14974676
TI  - Introduction and overview: sex steroids in the mammary gland.

PMID- 14974677
TI  - Introduction: models of premalignant breast disease.

PMID- 14974678
TI  - Substantial genetic effects involved in determination of circulating levels of
      calciotropic hormones in human pedigrees.
AB  - This paper reports the results of a series of univariate and bivariate
      statistical genetic analyses that were performed on a sample of nuclear and more
      complex pedigrees (N = 567 individuals) of an ethnically homogenous White
      population. Our major objectives were: (1) To quantitatively evaluate the extent
      and pattern of the putative genetic effects on plasma level variation and
      covariation of the intact parathyroid hormone (PTH) and 25-hydroxyvitamin D
      [25(OH)D]; (2) To evaluate the extent of the possible genetic covariation between
      each of the two calciotropic hormones and two important bone mass traits, namely
      radiographic hands bone mineral density (BMD) and cortical index (CI). Variance
      component analysis, as implemented in the statistical package FISHER unambigously
      demonstrated that in addition to age, genetic factors contribute significantly to
      interindividual variation of both calciotropic hormones (37.5% for PTH and 53.3%
      for 25(OH)D). Complex segregation analysis strongly suggested the involvement of
      major gene effects into the determination of 25(OH)D levels, but was not clear
      cut with respect to PTH. Significant correlations between circulating levels of
      study hormones were found (-0.146, P < 0.05 in men and -0.194, P < 0.01 in
      women). However, no genetic correlation was revealed between PTH and 25(OH)D
      plasma concentrations. Bivariate analyses showed that familial cross correlations
      between PTH and BMD and CI measured at the bones of the hand were consistently
      statistically significant, suggesting moderate, but detectable pleiotropic
      genetic effects. The corresponding genetic correlations were -0.461 +/- 0.153 and
      -0.223 +/- 0.113, respectively. Circulating levels of 25(OH)D showed neither
      phenotypic nor genetic correlation with any of the BMD or CI variation.

PMID- 14974679
TI  - A mini review of the high mobility group proteins of insects.
AB  - High mobility group (HMG) proteins are an abundant class of chromosomal proteins
      facilitate assembly of higher order structures. The mammalian HMG proteins have
      been grouped into three distinct families on the basis of their characteristic
      functional sequence: the HMGB, the HMGN, and the HMGA family. The HMG proteins of
      Drosophila melanogaster and Chironomus tentans are the best characterized
      dipteran insect HMG proteins. Three abundant members of this group of nonhistone
      proteins were detected in those insects. Two of them belong to the HMGB family
      and one to the HMGA family. The possible relatedness of these proteins to the
      formation of higher order nucleoprotein structures and their possible role in the
      regulation of transcription is discussed.

PMID- 14974680
TI  - Mitochondrial DNA control region and cytochrome b sequence variation in the genus
      Mystacoleucus Gunther (Pisces: Cyprinidae: Barbinae) from China.
AB  - Mitochondrial DNA (mtDNA) hypervariable segment I sequences (HVSI, 471 bp) of the
      control region and partial cytochrome b sequences (Cytb, 403 bp) were analyzed in
      three tentative species of the genus Mystacoleucus in China (M. chilopterus, M.
      marginatus, and M. lepturus). Not more than two mutations were found in both the
      HVSI and Cytb fragments among the samples from M. chilopterus and M. marginatus.
      However, M. lepturus differed from each of them by at least 25 mutations in Cytb
      and 51 mutations in HVSI. Moreover the HVSI sequence variation within M. lepturus
      was larger than that between M. chilopterus and M. marginatus. Given that M.
      chilopterus and M. marginatus are very similar in morphology, it is reasonable to
      consider M. chilopterus and M. marginatus as conspecific. Our results also
      suggest a recent radiation of M. marginatus from downstream to upstream of the
      Lancangjiang (Mekong) River.

PMID- 14974681
TI  - Cloning and identification of a novel human RNPC3 gene that encodes a protein
      with two RRM domains and is expressed in the cell nucleus.
AB  - The RNA recognition motifs (RRM) domain is one of the most common eukaryotic
      protein folds. Proteins containing RRM domains function in important steps of
      posttranscriptional regulation of gene expression and are involved in processing
      and transport of mRNA precursors. Here we describe the cloning and
      characterization of a novel human RNPC3 gene containing two RNA recognition
      motifs. The 1870 bp cDNA encodes a protein with 517 amino acids. It also contains
      two bipartite nuclear targeting sequences, which is important for nuclear
      targeting for proteins, especially those functioning in the cell nucleus. The GFP
      location of the RNPC3 gene product shows that this protein is located in the cell
      nucleus. RT-PCR reveals that it is abundantly expressed in kidney and pancreas.

PMID- 14974682
TI  - Quantitative trait locus analysis of plasma cholesterol and triglyceride levels
      in KK x RR F2 mice.
AB  - A previous quantitative trait locus (QTL) study on hyperlipidemia in C57BL/6J x
      KK-Ay/a F2 mice identified three significant cholesterol QTLs (Cq1 and Cq2 on
      chromosome 1, and Cq3 on chromosome 3), and a suggestive triglyceride QTL on
      chromosome 9. An alternative analysis of this study identified a novel
      cholesterol QTL on chromosome 9 (Cq4), and a significant triglyceride QTL on
      chromosome 9 (Tgq1). In the present study, QTL analysis was performed on KK x RR
      F2 mice. A significant cholesterol QTL (Cq5, lod score 5.6) was identified on
      chromosome 9, and a significant triglyceride QTL (Tgq2, lod score 4.7) was
      identified on chromosome 8. The Cq5 locus was mapped to a region similar to the
      Cq4 locus. On the other hand, the Tgq2 locus overlapped with the QTL region
      responsible for glucose intolerance (Giq1) that was identified in a previous
      study. The results suggest that a different combination of QTLs is involved in
      the trait when a different counterpart strain is used. Identification of
      distinct, but related traits in an identical chromosomal region will facilitate
      revealing the responsible gene.

PMID- 14974683
TI  - Genetic polymorphism of 11 allozyme loci in populations of wall lizards (Podarcis
      sp.) from the Iberian Peninsula and North Africa.
AB  - The taxonomy of Iberian and North African wall lizards (Podarcis sp.) has been
      controversial. Recently, morphological and mtDNA sequence data have provided new
      information on differentiation within these lacertids. To compare these results
      to those provided by nuclear markers, we investigated variation at 11 polymorphic
      protein loci using conventional electrophoresis and isoelectric focusing in 11
      populations belonging to seven different mtDNA lineages. A total of 62 alleles
      were found. Populations belonging to the same mtDNA type presented high genetic
      similarity, whereas strong differentiation was observed between groups. These
      results are consistent with those previously obtained from morphological and
      mtDNA analysis and support the idea that Iberian and North African Podarcis are
      composed of several well-differentiated entities, some of which are already
      recognized as species, whereas others (belonging to the P. hispanica complex)
      clearly need taxonomic revision.

PMID- 14974685
TI  - Tomato transgenic lines and Tetranychus urticae: changes in plant suitability and
      susceptibility.
AB  - A critical aspect dealing with the use of transgenic plants is the global
      evaluation of their environmental impact. The polyphagous mite Tetranychus
      urticae can be considered a suitable species to investigate unpredictable and
      undesirable effects on phytophagous arthropods. Three tomato near isogenic lines,
      that is, the cv. Riogrande (RIG), the transgenic lines RC332 (containing the Gox
      gene and showing high glucose oxidase activity), and MS498 (containing the KTI3
      gene and exhibiting a high trypsin inhibition) were used in laboratory and
      greenhouse trials. Trichomes and contents of C and N of the leaves, differences
      in development and oviposition of T. urticae and damage caused were evaluated for
      each line. The laboratory trials evidenced that (1) the intrinsic rate of
      increase of two strains of T. urticae (T from tomato, B from bindweed), reared on
      the lower surface of tomato leaflets, was significantly lower in RIG than in
      transgenic lines and doubling time ranged between 6.9 and 11.6 days in the first
      and between 3.9 and 5.3 days in the latter; (2) the glandular four-lobed
      trichomes were always higher in RIG than in other genotypes; (3) the N leaf
      content was from 1.3 to 1.9 fold lower and the C/N ratio from 1.3 to 1.9 fold
      higher in RIG than in other lines. The greenhouse experiment, that lasted over a
      month and was performed by inducing an initially equal infestation of strain T,
      evidenced: (1) no significant difference between plant lines in the final mite
      infestation (motile stages per plant), nevertheless an almost double number of
      spider mites was counted in RC332; (2) a significantly higher percentage of
      damaged leaves and a significant higher average damage index on RC332 than on RIG
      (79% and 2.3 in the former, and 62% and 2.1 in the latter, respectively), even if
      in both transgenics a higher level of the most severe damages and a shorter time
      to approach them were observed; (4) a comparable number of mites causing the same
      damage level in all genotypes and a strong linear relation between the first four
      levels of damage and mite infestation. Although in the laboratory studies both
      transgenic lines enhanced the T. urticae population increase, the glasshouse
      studies were not as conclusive and they only suggest the possibility of any real
      difference between the transgenic and non-transgenic genotypes.

PMID- 14974684
TI  - Development of genetic differentiation and postzygotic isolation in experimental
      metapopulations of spider mites.
AB  - We studied the development of genetic differentiation and postzygotic isolation
      in experimental metapopulations of the two-spotted spider mite, Tetranychus
      urticae Koch. A genetically diverse starter population was made by allowing six
      inbred sublines to interbreed. Then three migration patterns were tested: no
      migration, or one or three immigrants per subpopulation per generation.
      Variations in four traits were investigated: allozymes, acaricide resistance,
      diapause, and hatchability. In the allozymes, acaricide resistance, and diapause,
      genetic variation among subpopulations became high in metapopulations with no
      migration, but not in the others, which showed that one immigrant is enough to
      prevent genetic differentiation. Hatchability, which was decreased by
      interbreeding among the six sublines, gradually recovered in succeeding
      generations. In metapopulations with no migration, hatchability was reduced again
      after in-migration at the 15th generation. Different karyotypes or coadapted gene
      complexes can survive in different subpopulations by genetic drift, and both
      Wolbachia-infected and -noninfected subpopulations may be selected, which would
      lead to postzygotic isolation between isolated subpopulations. Our results
      indicate that sampling effects such as genetic drift or stochastic loss of
      Wolbachia produce postzygotic isolation in laboratory populations of spider mite.

PMID- 14974686
TI  - Oviposition model of overwintered adult Tetranychus urticae (Acari:
      Tetranychidae) and mite phenology on the ground cover in apple orchards.
AB  - The phenology of overwintered Tetranychus urticae was studied on the ground cover
      in apple orchards in the early season, and an oviposition model of overwintered
      adults was developed. The movement of overwintered adults from trees to ground
      cover started from mid-March and continued until mid-April. One life cycle from
      eggs to new adults (the 1st generation adults) on the ground cover was from late
      March to early May. The longevity and fecundity of overwintered T. urticae were
      affected largely by temperature. The longevity ranged from 46.6 days at 10
      degrees C to 6.5 days at 35 degrees C. The total fecundity was minimum (0.2 eggs)
      at 10 degrees C and maximum (45.5 eggs) at 25 degrees C. The relationship between
      total fecundity and temperature was described well by a nonlinear equation. The
      cumulative age-specific oviposition rate was described well by the two-parameter
      Weibull function. The overall adult survival exhibited a reverse logistic curve.
      Three temperature-dependent components, age-specific cumulative oviposition rate,
      temperature-dependent total fecundity and age-specific survival rate functions,
      were incorporated into an oviposition model. The oviposition model simulation
      described the occurrence pattern of eggs laid by overwintered T. urticae on the
      ground cover in apple orchards relatively well.

PMID- 14974687
TI  - Diapause and implications for control of Penthaleus species and Halotydeus
      destructor (Acari: Penthaleidae) in southeastern Australia.
AB  - Blue oat mites, Penthaleus spp., and redlegged earth mites, Halotydeus destructor
      (Tucker) are major winter pests of a variety of crops and pastures. In southern
      Australia earth mites exhibit a facultative egg diapause to survive unfavorable
      summer conditions. The initiation of diapause egg production in earth mites was
      investigated using field and shade-house experiments. Species differed in their
      timing of diapause. H. destructor mainly produced diapausing eggs towards the end
      of the active mite season in spring, although small numbers were also produced in
      winter. In contrast, Penthaleus major (Duges) produced diapause eggs almost
      immediately after emergence in autumn and continued producing these eggs
      throughout the season. Penthaleus falcatus (Qin and Halliday) also produced
      diapause eggs in early winter, although the first appearance of these eggs was
      slightly later in the season than for P. major. The diapause response of an
      undescribed species was also somewhat later than in P. major and P. falcatus, but
      earlier than in H. destructor. Electrophoresis of P. major samples indicated that
      clones of this parthenogenic species may differ in their timing of diapause egg
      production, providing another potential selective factor contributing to the
      maintenance of clonal diversity within this group. The results highlight the
      importance of determining species composition when devising control strategies
      for earth mite outbreaks.

PMID- 14974688
TI  - Interactions in an acarine predator guild: impact on Typhlodromalus aripo
      abundance and biological control of cassava green mite in Benin, West Africa.
AB  - To determine the impact of an acarine predator guild on the abundance of a shared
      herbivorous prey and its principal exotic predator, a series of surveys were
      conducted in ca. 200 cassava fields in swamp and non-swamp areas in southwestern
      Benin, West Africa. For each field, the surveys provided data on the density of a
      pest arthropod, the cassava green mite Mononychellus tanajoa (Bondar), of an
      introduced and successfully established natural enemy, the apex-inhabiting
      predatory mite Typhlodromalus aripo DeLeon, and on occurrence of other predator
      species that inhabit the leaves and share the same prey. These other predators
      included one exotic species, Typhlodromalus manihoti Moraes, that is successfully
      established mainly in swamp areas, and two indigenous species, Euseius fustis
      (Pritchard and Baker) and Typhlodromalus saltus (Denmark and Matthysse), that are
      commonly found on cassava in Africa. Our aim was to assess the association
      between the density of M. tanajoa and that of T. aripo, the most successful
      predator in terms of establishment and abundance, and subsequently determine how
      this association was affected by the presence or absence of the other predator
      species. No obvious density-dependent relationship was found by inspecting the
      scattergrams of T. aripo versus M. tanajoa densities, but high T. aripo densities
      did not occur when M. tanajoa densities were low and--during the dry season in
      February--the densities of M. tanajoa steeply increased when T. aripo numbers
      were low. Given the establishment of T. aripo in all fields, the presence of
      other species of predatory mites (T. manihoti, both in swamp and non-swamp areas;
      T. saltus in absence--as well as presence--of T. manihoti in swamp areas; E.
      fustis in absence of T. manihoti in non-swamp areas) reduced the density of M.
      tanajoa by a factor 2-3. Thus in all these cases, the presence of an exotic or
      indigenous species of predatory mite in addition to T. aripo was associated with
      lower M. tanajoa density. The density of T. aripo was usually positively affected
      by the presence of other predator species except for T. saltus in presence of T.
      manihoti that negatively affected the density of T. aripo in swamp areas, an
      effect likely mediated by either intraguild predation or competition for food.
      Path analysis showed that indigenous phytoseiid species were more important in
      suppression of M. tanajoa populations in cassava fields than previously thought.
      We suggest that the lack of negative effects of the predator species complex is
      likely due to differential niche use by the various species which reduces
      interference among the predators. Manipulative experiments are, however, needed
      to provide details on the relative importance in M. tanajoa suppression by each
      species within this acarine predator guild.

PMID- 14974689
TI  - Factors affecting mite herbivory on eggplants in Brazil.
AB  - The objective of this study was to determine effects of total rainfall, mean
      temperature, predators, height of canopy, levels of nitrogen and potassium in
      leaves, and the density of leaf trichomes on the attack intensity of Tetranychus
      evansi and T. urticae (Acari: Tetranychidae) and Aculops lycopersici (Acari:
      Eriophyidae) in five plantations of the eggplant Solanum melongena var. 'Natu
      Nobilis' in two regions of Brazil. Higher numbers of individuals of A.
      lycopersici, T. evansi and T. urticae/cm2 were observed on eggplants in the
      Municipality of Guidoval than in Vicosa which might be explained by the fact that
      Guidoval showed hotter and more rainy weather. A. lycopersici was positively
      correlated with mean temperature (r=0.54, P=0.03), and T. evansi was positively
      correlated with total rainfall (r=0.54; P=0.04), while for T. urticae the
      correlation with total rainfall was almost significant (r=0.47, P=0.055). No
      significant effects were found (P>0.05) of natural enemies, levels of N and K and
      leaf trichome density on population densities of mites. A. lycopersici showed
      higher density on the apical leaves while nymphs and adults of T. evansi and eggs
      of T. urticae had higher numbers on leaves of the apical and medium parts of
      eggplants than on the lower leaves. Nymphs and adults of T. urticae showed higher
      attack intensity on leaves from the medium and lower thirds of the plants.

PMID- 14974690
TI  - Influence of volunteer wheat plant condition on movement of the wheat curl mite,
      Aceria tosichella, in winter wheat.
AB  - The wheat curl mite (WCM), Aceria tosichella Keifer, is the vector of wheat
      streak mosaic virus and high plains virus which cause significant crop loss in
      winter wheat throughout the western Great Plains. Volunteer wheat emerging before
      harvest, as a result of severe hail, is the primary source of mites and virus
      that infect fall-planted winter wheat. Wind-borne movement of the WCM is of key
      importance in the spread and infection of the virus complex. Significant movement
      of WCM from wheat has been thought to be closely tied to the senescence or
      deterioration of the host. Results from field and greenhouse studies indicated
      that movement from un-vernalized winter wheat was not closely associated with the
      deterioration of the wheat host. Greenhouse studies showed no correlation between
      WCM movement and plant condition, but there was a highly significant relationship
      between WCM movement and mite population on the host plant. Field studies did not
      demonstrate increased movement associated with deteriorating un-vernalized winter
      wheat. However, healthier hosts which were able to support a larger population of
      mites were associated with increased movement. The main influence on the level of
      mite movement relates to the size of the source population and not the condition
      of the host plant, but plant condition appears to be a factor in limiting the
      increase of the WCM population.

PMID- 14974691
TI  - The reproductive program of female Varroa destructor mites is triggered by its
      host, Apis mellifera.
AB  - Reproducing Varroa females begin oviposition on a host larva by laying an
      unfertilized (male) egg, followed by fertilized (female) offspring. Using
      transfer experiments, we examined whether the sequence of sexes in the brood cell
      is triggered by a host stimulus. When reproducing Varroa females were transferred
      from white-eyed pupae (worker brood) into freshly capped worker brood cells, 77%
      (n = 22 fertile mites after the transfer) began a new reproductive cycle by
      laying a male egg. The proportion of brood cells with male offspring was similar
      to naturally infested brood cells. Varroa females transferred into brood cells
      with young pupae reproduced, but only 6% (n = 16 fertile mites after the
      transfer) produced male offspring. This was significantly different from male
      production in naturally reproducing Varroa females and those transferred into
      freshly capped brood cells. We conclude that a host stimulus present in freshly
      capped brood cells triggers both the start of reproduction and the sequence of
      sexes.

PMID- 14974692
TI  - Toxicity of imidacloprid to Galendromus occidentalis, Neoseiulus fallacis and
      Amblyseius andersoni (Acari: Phytoseiidae) from hops in Washington State, USA.
AB  - The toxicity of systemic and spray formulations of imidacloprid to Galendromus
      occidentalis Nesbitt, Neoseiulus fallacis Garman and Amblyseius andersoni (Chant)
      from hop yards in Washington State was evaluated in laboratory bioassays. The
      field rate of imidacloprid for hop aphids (0.13 g a.i. l) was highly toxic (100%
      mortality) to G. occidentalis and N. fallacis but less so (35.6% mortality) to A.
      andersoni. Half and quarter rates were also highly toxic to G. occidentalis and
      N. fallacis (79.5-100% mortality) but again had lower toxicity to A. andersoni
      (8.2-31.3% mortality). Systemic toxicity (via consumption of spider mite motiles
      feeding on leaf discs cut from imidacloprid-treated (0.13 g a.i. l) dwarf bean
      plants) was also high for G. occidentalis (98.3% mortality), as was toxicity from
      dried residues (93-98% mortality). Residual toxicity to N. fallacis was also high
      (89% mortality). The significance of these results for biological control of
      spider mites in hops and other crops is discussed.

PMID- 14974693
TI  - Amblyomma aureolatum and Ixodes auritulus (Acari: Ixodidae) on birds in southern
      Brazil, with notes on their ecology.
AB  - Between January 1999 and December 2000, 876 bird specimens were captured in three
      different ecological environments from the Reinhard Maack Park, Curitiba, State
      of Parana, southern Brazil. A total of 142 birds (16.2%) were infested with
      Amblyomma aureolatum (Pallas 1772) (N=699) and/or Ixodes auritulus Neumann, 1904
      (N=18) ticks. Questing A. aureolatum nymphs (N=2) and adults (N=5) were also
      collected from the soil and the vegetation. None of the I. auritulus were
      collected off-host. We collected only immatures of A. aureolatum on birds, but
      all life stages of I. auritulus. The latter species was collected on Turdus
      rufiventris and on Synallaxis ruficapilla, which is herein recognized as a host
      of I. auritulus for the first time. Moreover, this is also the first report of A.
      aureolatum infesting birds, and 16 different bird species were found infested. It
      was observed that larval infestation was positively correlated with the dry and
      cold season, while nymphal infestation was positively correlated with the warm
      and rainy season. Although only 2-years worth of data is provided, our results
      suggest the infestation of birds by ticks was significantly higher at the
      biotopes formed by forest at its first stage of regeneration 'capoeira' and the
      original Araucaria forest habitat 'mata' than the ecotone between forest and
      urban areas 'peripheral area'.

PMID- 14974695
TI  - Media coverage of the quintessence breasffeeding challenge.

PMID- 14974694
TI  - Experimental immunisation of crossbred cattle with glycoproteins isolated from
      the larvae of Hyalomma anatolicum anatolicum and Boophilus microplus.
AB  - In India, control of tick infestations is a major problem facing the owners of
      highly productive crossbred cattle. To develop suitable immunoprotective measures
      against the multitick infestations, specific problem encountered by the Indian
      farmers, an attempt has been made to identify candidate protein molecules in the
      larvae of Hyalomma anatolicum anatolicum and Boophilus microplus. Employing two
      steps affinity chromatography method, glycoproteins of 34 and 29 kDa were
      isolated from H. a. anatolicum and B. microplus, respectively. The additive
      effect of the isolated glycoproteins was tested by the immunisation of crossbred
      male calves at a dose of 200 microg/animal of each glycoprotein, three divided
      dosages. Following challenge infestations by the stages of two species of ticks,
      a significant rejection of (73.6%; P < 0.01) of larvae and adults (75.0%; P <
      0.01) of H. a. anatolicum and adults (89.8%; P < 0.01) of B. microplus were
      noted. The direct effect of immunisation on the stages of the challenged ticks
      (%DT) was calculated as 69%, 52% against larvae and adults of H. a. anatolicum
      and 60% against adults of B. microplus. A direct corelation between protection
      and anti-glycoprotein antibody titre was detected. The effect of the isolated
      glycoproteins on limiting the tick infestation is discussed in detail.

PMID- 14974696
TI  - Exclusive breastfeeding rates and associated factors in Swiss baby-friendly
      hospitals.
AB  - Monitoring of infant feeding and related health care practices was introduced in
      all 28 Swiss Baby-Friendly Hospitals to assess exclusive breastfeeding rates and
      potentially associated factors. Data on 5790 neonates were collected in 1999, and
      rates of exclusive breastfeeding in different health facilities were calculated.
      Odds ratios were calculated to estimate the effects of different determinants on
      exclusive breastfeeding rates. Of all infants, 97% were initially breastfed, but
      only 38% were exclusively breast milk fed in Baby-Friendly maternity wards, and
      proportions varied from 8% to 85% among hospitals. The strongest determinants for
      exclusive breastfeeding were health facility factors. Furthermore, exclusive
      breastfeeding rates significantly increased with every month of monitoring
      duration. The findings suggest that the introduction of continuous monitoring of
      infant nutrition and related health care practices might have a positive effect
      on breastfeeding management in health facilities.

PMID- 14974697
TI  - High prepregnant body mass index is associated with poor lactation outcomes among
      white, rural women independent of psychosocial and demographic correlates.
AB  - To determine whether high prepregnant body mass index (BMI) is associated with
      later onset of lactogenesis II (LGII) and shorter duration of breastfeeding, we
      questioned 151 women about their demographic and psychosocial characteristics
      during pregnancy and about the onset of LGII during days 1 to 5 postpartum.
      Compared to women with earlier (< 72 hours) onset of LGII, those with later onset
      had a higher BMI (P < .05), a higher proportion of primiparity (P < .01), and a
      lower infant score on the Mother-Baby Assessment (P < .05). Prepregnant BMI (P <
      .04) and primiparity (P < .005) were each associated with later onset of LGII,
      but only primiparity remained significant when both factors were considered
      simultaneously. These results suggest that, in addition to those who have just
      delivered their first infant, those with higher prepregnant BMI values also
      warrant extra support to decrease their risk of early discontinuation of
      breastfeeding.

PMID- 14974698
TI  - Breastfeeding duration in an Australian population: the influence of modifiable
      antenatal factors.
AB  - Despite well-documented health benefits of breastfeeding for mothers and babies,
      most women discontinue breastfeeding before the recommended 12 months to 2 years.
      The purpose of this study was to assess the effect of modifiable antenatal
      variables on breastfeeding outcomes. A prospective, longitudinal study was
      conducted with 300 pregnant, Australian women. Questionnaires containing
      variables of interest were administered to women during their last trimester;
      infant feeding method was assessed at 1 week and 4 months postpartum. Intended
      breastfeeding duration and breastfeeding self-efficacy were identified as the
      most significant modifiable variables predictive of breastfeeding outcomes.
      Mothers who intended to breastfeed for < 6 months were 2.4 times as likely to
      have discontinued breastfeeding at 4 months compared to those who intended to
      breastfeed for > 12 months (35.7% vs 87.5%). Similarly, mothers with high
      breastfeeding self-efficacy were more likely to be breastfeeding compared to
      mothers with low self-efficacy (79.3% vs 50.0%).

PMID- 14974699
TI  - Social capital, acculturation, and breastfeeding initiation among Puerto Rican
      women in the United States.
AB  - To examine reasons for not breastfeeding, and to identify factors associated with
      ever breastfeeding among Puerto Rican women, a retrospective study was done using
      a convenience sample of 161 low-income Latino women with children younger than 6
      years. Women were recruited from the Hispanic Health Council (43.5%), the
      Supplemental Nutrition Program for Women, Infants, and Children (29.8%), and
      other places (26.7%). Participants were interviewed using a pretested
      questionnaire specific to the target community. Most (73%) of the respondents
      chose to be interviewed in Spanish. Chi-square analyses were used to examine the
      bivariate association between ever breastfeeding and the independent variables.
      Multivariate logistic regression was conducted to estimate the independent
      association between acculturation, social capital, and breastfeeding. Women with
      more social capital were more likely (odds ratio = 2.25, 95% confidence interval,
      1.02-4.95) to have breastfed the index child, suggesting that social capital is
      an important predictor of breastfeeding initiation in this community.

PMID- 14974700
TI  - Couples' relationships and breastfeeding: is there an association?
AB  - One hundred fifty-three Brazilian families with 4-month-old infants--51 cases
      (breastfeeding had ceased) and 102 controls (breastfeeding maintained)--were
      recruited to verify if a problematic couple relationship is associated with early
      breastfeeding termination. The relationships of the 118 cohabiting couples were
      assessed by clinical interviews and the Global Assessment of Relational
      Functioning and Beavers-Timberlawn scales, examining marital and parental
      functions, parents' satisfaction with the quality of care each partner provided
      to their infants, mothers' opinions of paternal breastfeeding support, and
      interviewers' assessments of paternal breastfeeding support and involvement in
      the infants' care. The quality of a couple relationship was not associated with
      the interruption of breastfeeding before 4 months postpartum. However, a good
      couple relationship was associated with more paternal breastfeeding support (P <
      .01) and involvement in the infant's care (P < .0001).

PMID- 14974701
TI  - Practices of vitamin D recommendation in Las Vegas, Nevada.
AB  - Reports of vitamin D deficiency rickets, although rare in the United States, have
      increased over the past few years, including in children living in climates with
      abundant sunshine. The purpose of this study was to describe vitamin D
      recommendation practices among pediatric health care providers in Las Vegas,
      Nevada. Of the 155 providers surveyed, 52.3% did not recommend vitamin D for
      exclusively breastfed babies. Providers who were more likely to recommend
      supplementation were doctors of medicine, were female, specialized in pediatrics,
      were of Hispanic ethnicity, had previously practiced and trained in states less
      sunny than Nevada, had graduated from training 21 or more years previously, had
      taken histories of infants' sun exposure, and had clinical experience with cases
      of rickets. Providers demonstrated a knowledge deficitforquestions that dealt
      with preventive measures.

PMID- 14974702
TI  - Methadone maintenance and lactation: a review of the literature and current
      management guidelines.
AB  - Methadone offers significant therapeutic benefits to the population of pregnant,
      opiate-dependent women and is currently the treatment of choice for this group.
      Yet the problem of women who elect to breastfeed while on methadone maintenance
      frequently vexes providers. Although breast milk offers advantages clearly
      beneficial to the general population of infants, there is debate about
      recommending breastfeeding to postpartum women receiving methadone maintenance.
      Although previous research has shown that amounts of methadone in breast milk
      appear to be very small, and therefore breastfeeding seems to be safe, women on
      methadone do not often breastfeed, for a variety of reasons. This article
      provides an overview of the issues facing providers in treating methadone
      maintained women who elect to breastfeed. A comprehensive review of existing
      literature on the subject is offered, along with clinical advice for
      practitioners providing care to this population of women and children.

PMID- 14974703
TI  - How can kangaroo mother care and high technology care be compatible?

PMID- 14974704
TI  - Stories of success: the use of donor milk is increasing in North America.
AB  - Donor milk has been used to successfully treat a number of medical conditions in
      infants. This article highlights 3 such success stories describing the use of
      human milk in cases of velocardiofacial syndrome, very-low-birth weight, and
      failure to thrive. In 2002, more than 300 infants and young children and 15
      adults received donor milk from 6 milk banks in the United States and I milk bank
      in Canada. Donor milk is often used to ensure optimal outcomes in full term or
      preterm infants until their own mother's milk volume is sufficient to meet their
      needs. However, human milk may be a lifesaving therapy for infants and young
      children with unusual medical conditions.

PMID- 14974705
TI  - Statistical report of the 2003 IBLCE examination.

PMID- 14974706
TI  - [Adult stem cells. Prospects for the therapy].

PMID- 14974707
TI  - [Ethical problems of stem cell research. A theological contribution].

PMID- 14974708
TI  - [Symposium. "Adult stem cell therapy", Monchengladbach, 6/28/2003].

PMID- 14974709
TI  - Electron transfer interaction of dihydroxyquinones with amine quenchers:
      dependence of the quenching kinetics on the aliphatic and aromatic nature of the
      amine donors.
AB  - Studies on the electron transfer (ET) interaction of 1,4-dihydroxy-9,10
      anthraquinone and 6,11-dihydroxy-5,12-naphthacenequinone with aliphatic and
      aromatic amine (AlA and ArA, respectively) donors have been investigated in
      acetonitrile solutions. Steady-state (SS) measurements show quenching of the
      quinone fluorescence by amines, without indicating any change in the shape of the
      fluorescence spectra. No significant change in the absorption spectra of the
      quinones is also observed in the presence of the amines. For all the quinone
      amine pairs, the bimolecular quenching constants (kq) estimated from SS and time
      resolved measurements are found to be similar. Variation in the kq values with
      the oxidation potentials of the amines indicates the involvement of the ET
      mechanism for the quenching process. A reasonably good correlation between the kq
      values and the free energy changes (deltaG0) for the ET reactions following
      Marcus' outer-sphere ET theory also supports this mechanism. It is seen that for
      both the quinone-ArA and quinone-AlA systems, the kq values initially increase
      and then get saturated at some diffusion-controlled limiting values (kqDC) as
      deltaG0 values gradually become more negative. Interestingly, however, it is seen
      that the kqDC value for the quinone-AlA systems is substantially lower than that
      for quinone-ArA systems. Such a large difference in the kqDC values between
      quinone-AlA and quinone-ArA systems is quite unusual. Present results have been
      rationalized based on the assumption that an orientational restriction is imposed
      for the encounter complexes in quinone-AlA systems to undergo ET reactions, which
      arises because of the localized (at amino nitrogen) shapes of the highest
      occupied molecular orbitals (HOMO) of AlA in comparison to the pi-like HOMO of
      the ArA.

PMID- 14974710
TI  - Fluorescence polarization studies of B-phycoerythrin oriented in polymer film.
AB  - Polarized steady-state fluorescence and fluorescence excitation spectra as well
      as time-resolved fluorescence for B-phycoerythrin (B-PE) from red algae,
      Porphyridium cruentum, embedded in polyvinyl stretched films were measured. The
      lifetimes of polarized fluorescence were analyzed using exponential components
      and fractal models. The interactions between various chromophores of the pigment
      protein complexes investigated were discussed. The anisotropy of fluorescence
      excitation spectra differs from the anisotropy of absorption spectra and depends
      on the wavelength of observation. This shows that differently oriented
      chromophores take part in various paths of excitation energy transfer (ET) or
      change their excitation into heat with various efficiencies (or both). Also,
      analysis of time-resolved fluorescence measured in various spectral regions gives
      different polarized components of emission. Fractal analysis of lifetimes, done
      under supposition of the Foerster resonance ET mechanism, suggests different
      arrangements of energy donors and acceptors for molecules absorbing in different
      spectral regions. It shows that several fractions of differently oriented "forms"
      of chromophores exhibiting different spectral properties occur in B-PE complexes.
      Small changes in the orientation of the chromophores can be followed by
      modification of the path of excitation energy migration. Based on the results
      obtained a new reorientational mechanism of the State 1 --> State 2 transition
      was proposed: Even small conformational modifications of biliproteins, which
      could be caused in vivo by the change in the conditions of preillumination of
      bacteria, are able to modify the path of excitation ET. Such a reorientation may
      be responsible for the change in the partition of biliprotein excitation energy
      between photosystem II (PSII) and PSI (State 1 --> State 2 transition). The
      proposed mechanism needs further verification by the investigation of whole
      bacteria cells.

PMID- 14974711
TI  - Generation of fluorescent adducts of malondialdehyde and amino acids: toward an
      understanding of lipofuscin.
AB  - Lipofuscin is a yellow-brown, highly fluorescent pigment that undergoes an age
      related progressive accumulation in animal cells, mainly in postmitotic cells. It
      is a heterogeneous, high-molecular weight material associated with proteins,
      lipids and nucleic acids. Lipofuscin is implicated in many aspects of human
      health, including aging, oxidative stress, macular degeneration, lipid
      peroxidation, atherosclerosis, dementia (Alzheimer's Disease) and diseases
      associated with prions. Although the fluorescent properties of lipofuscin have
      long been recognized, neither histologists nor chemists have yet isolated the
      pigments themselves or characterized their optical properties. We have prepared
      lipofuscinlike species by reacting malondialdehyde (MDA) with cysteine (Cys).
      MDA:Cys adducts 3:2 and 2:2 are two of those that have been identified among the
      many that were present in the reaction. Whereas previous attempts to synthesize
      lipofuscinlike species resulted in compounds that were either nonfluorescent or
      emitted principally in the blue, the MDA:Cys adducts reported in this study are
      not only fluorescent but also emit over a broader range.

PMID- 14974712
TI  - Coupling of climate change and biotic UV exposure through changing snow-ice
      covers in terrestrial habitats.
AB  - During the spring, when ozone depletion at the polar regions is at its maximum
      and consequently the environmental UV exposure is potentially high, many
      terrestrial communities are covered in snow and heterogeneous snow-encrusted ice
      that form near the edges of snowpack. Using field measurements and a theoretical
      radiative transfer model, we calculated the thicknesses of these covers that are
      necessary to reduce DNA-weighted dose to levels equal to or lower than those
      received later in the season in the absence of covers when there is no ozone
      depletion. This depth is approximately 4 cm for a 60% depletion of the ozone
      column, suggesting that even thin snow-ice covers are enough to completely cancel
      the biological effects of ozone depletion. Loss of snow-ice covers during early
      summer can be rapid. The maximum rate of retreat of snow cover measured during
      November at Mars Oasis, Antarctica (71.9 degrees S, 68.2 degrees W), was 44.1
      cm/day, with a mean retreat of 15.4 cm/day. Climate warming might increase UV
      radiation damage by melting UV-protecting terrestrial snow-ice covers earlier in
      the season, when ozone depletion is more severe. Conversely, climate cooling
      could increase UV-protection afforded to terrestrial communities by increasing
      the extent of snow and ice covers. Even if anthropogenic ozone depletion is
      eventually reversed, these data suggest the importance of climate forcing in
      determining UV exposures of terrestrial microbial communities in snow- and ice
      covered environments.

PMID- 14974713
TI  - Global Solar UV Index: Australian measurements, forecasts and comparison with the
      UK.
AB  - The 2002 revision of the UV index (UVI) issued by the World Health Organisation
      (WHO), the World Meteorological Office (WMO), the United Nations Environment
      Programme (UNEP) and the International Commission on Non-Ionizing Radiation
      Protection (ICNIRP) (World Health Organization [2002] Global Solar UV Index: A
      Practical Guide. WHO, Geneva) was motivated by the need to further standardize
      the use and presentation of the UVI. Awareness of the hazards of solar UV
      radiation (UVR) is generally high in Australia, but more effective use of the UVI
      will assist in promoting further changes to the population's sun exposure
      behavior. UVI levels for a number of cities around Australia as measured by the
      Australian Radiation Protection and Nuclear Safety Agency (ARPANSA), covering the
      time period 1996-2000, are presented. Also shown are UVI forecasts from the
      Australian Bureau of Meteorology (BOM). Agreement between the BOM data and the
      measurements varies depending on the location but is within 2 UVI units
      approximately 75% of the time. UVI levels are supplied to the media, and in
      summer values in excess of 12-14 are regularly recorded, although the more
      northerly locations occasionally reach 16 and 17. The factors affecting the solar
      UVR environment and the measured UVI are also discussed and compared against
      measurements from the UK.

PMID- 14974714
TI  - Modeling the anatomical distribution of sunlights.
AB  - One of the major technical challenges in calculating solar irradiance on the
      human form has been the complexity of the surface geometry (i.e. the surface
      normal vis-a-vis the incident radiation). Over 80% of skin cancers occur on the
      face, head, neck and back of the hands. The quantification, as well as the
      mapping of the anatomical distribution of solar radiation on the human form, is
      essential if we are to study the etiology of skin cancers or cataracts or immune
      system suppression. Using advances in computer graphics, including high
      resolution three-dimensional mathematical representations of the human form, the
      calculation of irradiance has been attained to subcentimeter precision. Lighting
      detail included partitioning of direct beam and diffuse skylight, shadowing
      effects and gradations of model surface illumination depending on model surface
      geometry and incident light angle. With the incorporation of ray-tracing and
      irradiance algorithms, the results are not only realistic renderings but also
      accurate representations of the distribution of light on the subject model. The
      calculation of light illumination at various receptor points across the anatomy
      provides information about differential radiant exposure as a function of subject
      posture, orientation relative to the sun and sun elevation. The integration of a
      geodesic sun-tracking model into the lighting module enabled simulation of
      specific sun exposure scenarios, with instantaneous irradiance, as well as the
      cumulative radiant exposure, calculated for a given latitude, date, time of day
      and duration. Illustration of instantaneous irradiance or cumulative radiant
      exposure is achieved using a false-color rendering--mapping light intensity to
      color--creating irradiance or exposure isopleths. This approach may find
      application in the determination of the reduction in exposure that one achieves
      by wearing a hat, shirt or sunglasses. More fundamentally, such an analysis tool
      could provide improved estimates of scenario-specific dose (i.e. absorbed radiant
      exposure) needed to develop dose-response functions for sunlight-induced disease.

PMID- 14974715
TI  - Role of p38 mitogen-activated protein kinase and caspases in UV-B-induced
      apoptosis of murine peritoneal macrophages.
AB  - The mechanisms of ultraviolet-B (UV-B)-induced apoptosis and the role of p38
      mitogen-activated protein kinase (MAPK) were investigated in murine peritoneal
      macrophages. Exposure of murine peritoneal macrophages to UV-B irradiation
      induced rapid apoptosis concurrent with DNA fragmentation and activation of
      caspase-3 but did not activate caspase-1. UV-B irradiation (100 mJ/cm2) also
      induced expression of phospho-p38 and -c-Jun N-terminal kinase (JNK) MAPK;
      however, no significant expression of phospho-p42/44 was observed 120 min after
      exposure. Pretreatment of macrophages with a p38 MAPK inhibitor, 4-(4
      fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole (SB202190), and a
      caspase-3 inhibitor, N-acetyl-Asp-Glu-Val-Asp-CHO, suppressed UV-B irradiation
      induced apoptosis as observed by DNA laddering and DNA fragmentation estimation
      quantitatively. Pretreatment with caspase-1 inhibitor, N-acetyl-Tyr-Val-Ala-Asp
      CHO, had no effect. UV-B-induced caspase-3 activation resulted in the cleavage of
      poly-(ADP-ribose) polymerase (PARP), which was inhibited by the caspase-3
      inhibitor. SB202190 pretreatment also prevented activation of caspase-3 and the
      cleavage of PARP. However, the caspase-3 and -1 inhibitors did not affect UV-B
      induced expression of phospho-p38 and -JNK. These results suggest that activation
      of p38 MAPK upstream of caspases might play an important role in the apoptotic
      process of macrophages exposed to UV-B irradiation.

PMID- 14974716
TI  - Diastereoselective self-aggregation of synthetic 3-(1-hydroxyethyl)
      bacteriopyrochlophyll-a as a novel photosynthetic antenna model absorbing near
      the infrared regions.
AB  - 3-Deacetyl-3-(1-hydroxyethyl)bacteriopyrochlorophyll-a (1), 7,8
      dihydrobacteriochlorophyll-d possessing 8-ethyl, 12-methyl and 17(4)-phytyl
      groups, was prepared by modifying naturally occurring bacteriochlorophyll-a. The
      synthetic 3(1)-epimers were separated by high-performance liquid chromotagraphy,
      and the absolute configuration at the 3(1)-position was determined by
      derivatization of 1 to a structurally determined chlorin. A dichloromethane
      solution of 3(1)R-1 or 3(1)S-1 was diluted with a 1000-fold volume of cyclohexane
      to give self-aggregation species absorbing light at a near-infrared (NIR) region
      (<910 nm). The resulting Qy maximum in 3(1)R-1 was 860 nm and redshifted by 2170
      cm(-1) from the monomeric one, whereas epimeric 3(1)S-1 showed a less redshifted
      peak at ca 800 nm, with a small dimeric band around 740 nm. Such visible spectra
      indicated that 3(1)R/S-1 formed different supramolecular structures in the self
      aggregates. In contrast, self-aggregation of the 7,8-dehydro-compound 2,
      bacteriochlorophyll-dP, found in natural antennas of photosynthetic green
      bacteria showed much smaller diastereomeric control. The self-aggregates of 3(1)R
      1 absorbing light in the NIR region would be models of intrinsic membraneous
      light-harvesting complexes 1 in photosynthetic purple bacteria as well as
      extramembranous antennas in green bacteria.

PMID- 14974717
TI  - Fluorescence lifetimes and spectral properties of protochlorophyllide in organic
      solvents in relation to the respective parameters in vivo.
AB  - In this work, absorption and fluorescence spectra of protochlorophyllide
      (Pchlide), as well as its fluorescence lifetime, were investigated in organic
      solvents having different physical properties. The obtained Pchlide spectral
      features are discussed in relation to the parameters describing solvent
      properties (refractive index and dielectric constant) and taking into account the
      specific solvent-Pchlide interaction. The correlation of Pchlide Qy and Soret
      absorption bands with solvent polarizability function ((n2 - 1)/(n2 + 2)) has
      been found; however, the dispersion of the observed points was rather high. A
      small Stokes shift of a magnitude between 50 and 300 cm(-1) was found, which
      indicates low sensitivity of Pchlide to nonspecific solvation. The fluorescence
      decay of Pchlide was single exponential in all the investigated solvents, with
      the lifetime value ranging from 5.2 ns for dioxane to 3.5 ns for methanol.
      Dependence of the obtained fluorescence lifetimes on the solvent orientation
      polarizability, a parameter being the function of both refractive index and
      dielectric constant, was discussed. In water-methanol mixtures, a further
      decrease of the fluorescence lifetime was observed, giving values of 2.9 ns for
      25% methanol. Double-exponential decay of Pchlide fluorescence was found for
      Pchlide in a solution of 15% methanol with the lifetimes of 4.5 +/- 0.5 ns and
      1.2 +/- 0.3 ns and in pure water with the lifetimes of 2.5 +/- 0.5 ns and 0.4 +/-
      0.1 ns. The obtained results are discussed in relation to spectroscopic
      properties of Pchlide in vivo.

PMID- 14974718
TI  - Multichannel flash spectroscopy of the reaction centers of wild-type and mutant
      Rhodobacter sphaeroides: bacteriochlorophyllB-mediated interaction between the
      carotenoid triplet and the special pair.
AB  - Multichannel flash spectroscopy (with microsecond time resolution) has been
      applied to carotenoid (Car)-containing and Car-less reaction centers (RC) of
      Rhodobacter sphaeroides with a view to investigate the interaction between the
      Car and its neighboring pigments at room temperature. Under neutral redox
      potential conditions, where the primary quinone acceptor (QA) is oxidized, the
      light-induced spectral changes in the 350-1000 nm region are attributed to the
      photochemical oxidation of the special pair (denoted here as P870), the
      generation of P870(+)QA(-), and the attendant electrochromism of adjacent
      chromophores. A bathochromic shift of <1 nm in the visible absorption region of
      Car reveals the sensitivity of Car to the P870 photooxidation. Under low redox
      potential conditions, where QA is reduced, P870 triplets (P870(+)) are formed.
      The time-resolved triplet-minus-singlet (TmS) spectrum of Car-less RC shows a
      deep bleaching at 870 nm, which belongs to P870(+), and additional (but smaller)
      bleaching at 800 nm; the entire spectrum decays at the same rate (with a lifetime
      of about 50 micros). The bleaching at 800 nm arises from the pigment interaction
      between P870(+) and the accessory bacteriochlorophylls on A and B branches
      (BA,B). In Car-containing RC, the TmS spectra of Car are accompanied by two
      smaller, negative signals--a sharp peak at 809 +/- 2 nm and a broad band at 870
      nm--which decay at the same rate as the TmS spectrum of Car (ca 10 micros). The
      former is ascribed to the perturbation, by Car(+), of the absorption spectrum of
      BB; the latter, to the TmS spectrum of P870(+), a species that appears to be in
      approximate thermal equilibrium with Car(+). These assignments are consistent
      with the absorption-detected magnetic resonance spectra obtained by other workers
      at low temperatures.

PMID- 14974719
TI  - Assessment of cellular response to thermal laser injury through bioluminescence
      imaging of heat shock protein 70.
AB  - Assessment of laser-induced tissue damage is not complete without an
      investigation into the resulting cellular and molecular changes. In the past,
      tissue damage was quantified macroscopically by visual effects such as tissue
      mass removal, carbonization and melting. Microscopically, assessment of tissue
      damage has been typically limited to histological analysis of excised tissue
      samples. In this research, we used heat shock protein (hsp70) transcription to
      track cellular response to laser-induced injury. A stable cell line (NIH-3T3) was
      generated containing the firefly luciferase (luc) reporter gene attached to the
      hsp promoter (murine hsp70a1). After thermal injury with a pulsed holmium-yttrium
      aluminum garnet laser (lambda = 2.1 microm, taup = 250 micros, 30 pulses, 3 Hz),
      luciferase is produced on hsp70 activation and emits broad-spectrum
      bioluminescence over a range of 500-700 nm, with a peak at 563 nm. The onset of
      bioluminescence can be seen as early as 2 h after treatment and usually peaks at
      8-12 h depending on the severity of heat shock. The luminescence was quantified
      in live cells using bioluminescence imaging. A minimum pulse energy (65 mJ/pulse
      [total energy 1.95 J; total radiant exposure = 6 J/cm2]) was needed to activate
      the hsp70 response, and a higher energy (103 mJ/pulse [total energy 3.09 J; total
      radiant exposure = 9.6 J/cm2]) was associated with a reduction in hsp70 response
      and cell death. Bioluminescence levels correlated well with actual hsp70 protein
      concentrations as determined by enzyme-linked immunosorbent assay. Photon counts
      were normalized to the percentage of live cells by means of a flow cytometry cell
      viability assay. Within a relatively small range between a lower activation
      threshold and an upper threshold that leads to cell death, the hsp70 response
      followed an Arrhenius relationship when constant-temperature water bath and laser
      experiments were carried out.

PMID- 14974720
TI  - Effects of UVR and UVR-induced cytokines on production of extracellular matrix
      proteins and proteases by dermal fibroblasts cultured in collagen gels%.
AB  - Synthesis of extracellular matrix (ECM) proteins and their degradation by matrix
      metalloproteinases (MMP) are part of the dermal remodeling resulting from chronic
      exposure of skin to ultraviolet radiation (UVR). We have compared two alternative
      mechanisms for these responses, namely, a direct mechanism in which UV-B or UV-A
      is absorbed by fibroblasts and an indirect mechanism in which cytokines, produced
      in skin in response to UVR, stimulate production of the ECM proteins and MMP.
      These studies were carried out on human dermal fibroblasts grown in contracted,
      free-floating 9 day old collagen gels as a dermal equivalent. Synthesis of
      tropoelastin, collagen, fibrillin, MMP-1, -2, -3 and -9 and tissue inhibitors of
      metalloproteinases (TIMP)-1 and -2 were measured. Tropoelastin, collagen and
      fibrillin levels were stable between days 4 and 10, and MMP and TIMP decreased by
      day 10. Neither UV-B (2.5-50 mJ/cm2) nor UV-A (2-12 J/cm2) altered synthesis of
      ECM proteins, but UV-A increased MMP-1 and -3 production. Tropoelastin synthesis
      increased in response to transforming growth factor-beta1 (5 ng/mL) treatment.
      Both interleukin-1beta and tumor necrosis factor-alpha (10 ng/mL) decreased
      fibrillin messenger RNA levels but increased MMP-1, -3 and -9 synthesis markedly.
      Collagen synthesis was not modulated by UV-B, UV-A or cytokine treatment. These
      results indicate that certain cytokines may have greater effects on production of
      ECM proteins and MMP than absorption of UV-B and UV-A by fibroblasts grown in
      dermal equivalents and suggest that the former pathway may play a role in the
      dermal remodeling in photoaged skin.

PMID- 14974721
TI  - Squaraine dyes for photodynamic therapy: mechanism of cytotoxicity and DNA damage
      induced by halogenated squaraine dyes plus light (>600 nm).
AB  - Halogenated squaraine dyes 1 and 2 possess favorable photophysical and in vitro
      photobiological properties that make these new class of molecules interesting for
      photodynamic therapeutic applications. For a better understanding of the
      mechanism of their photobiological activity, we have analyzed the DNA damage and
      the cytotoxicity induced by these photosensitizers in mammalian cells and cell
      free systems in the presence and absence of various additives and scavengers.
      Both photoactivated squaraines were found to be similar efficient in inducing
      single-strand breaks (SSB) in cell-free DNA when compared with the cellular DNA.
      Superoxide dismutase and catalase did not show any influence. However, the
      presence of tert-butanol and glutathione inhibited the formation of the DNA SSB,
      indicating an indirect (possibly squaraine radical mediated) mechanism under cell
      free conditions. Replacing H2O in the buffer by D2O resulted in a five- to six
      fold increase in the number of the SSB in cell-free DNA and a significant
      enhancement of the photocytotoxicity in mouse lymphoma cells. The results
      demonstrate that singlet oxygen is the major reactive species under cell-free and
      cellular conditions and confirm that squaraine-based sensitizers 1 and 2 can have
      potential applications in photodynamic therapy.

PMID- 14974722
TI  - The effect of photofrin on DNA strand breaks and base oxidation in HaCaT
      keratinocytes: a comet assay study.
AB  - Photodynamic therapy (PDT) kills cells via the production of singlet oxygen and
      other reactive oxygen species. PDT causes chromosomal damage and mutation to
      cultured cells. However, DNA damage does not contribute to the phototoxic effect.
      To study the effect of Photofrin-PDT-induced DNA damage, we used the comet assay
      in combination with endonuclease III and formamidopyrimidine DNA glycosylase and
      a human keratinocyte cell line to investigate photogenotoxicity and its
      prevention by tocopherol (TOC). This study shows that PDT induced DNA damage in
      HaCaT cells at doses allowing cells to survive 7 days after irradiation. alpha
      TOC did not prevent the acute cell lysis caused by Photofrin-PDT but did prevent
      Photofrin-PDT-induced DNA damage. However, the concentration of TOC that
      conferred protection (100 microM) was higher than is detected in human serum.
      Base oxidation was also measured using the comet assay. Although TOC could
      prevent frank DNA strand breaks caused by PDT, it was unable to decrease the
      level of base oxidation as revealed by enzyme-sensitive sites. It is suggested
      that the potential genotoxic risk from laser-PDT could be low, and that topical
      micro-TOC at a high concentration may be useful in preventing some types of DNA
      damage without preventing acute photolysis after Photofrin-PDT.

PMID- 14974724
TI  - Oxygen triggering reversible modulation of Vibrio fischeri strain Y1
      bioluminescence in vivo.
AB  - Yellow-emitting Vibrio fischeri Y1 modulates its bioluminescence (BL) depending
      on the dissolved O2 concentration. On supplying O2 to the cells under
      anaerobiosis, the cells begin to emit striking yellow BL peaking around 535 nm.
      The enhanced yellow emission reverts reversibly to the original level after O2 is
      consumed. Moreover, the reversible rise and fall of the yellow emission occurs
      repeatedly in accord with the repeating cycles of aeration on and off. This
      indicates that an increase in the cellular amount of yellow fluorescent protein
      (YFP) is not an immediate cause of the yellow emission enhancement. One suggested
      explanation is that the activity of YFP originating from its highly fluorescent
      property is altered by redox interaction with the respiratory components,
      including the soluble cytochrome c. Under the O2-limited conditions, the cellular
      YFP molecules, in part, seem to lose the fluorescent property possibly because of
      being reduced via redox interaction with some respiratory components in reduced
      form. On stimulating aerobic respiration with O2 supply, the reduced YFP seems to
      retrieve its fluorescent property via oxidation possibly with both O2, diffused
      across the cell membrane, and ferricytochrome c, generated during the respiratory
      turnover. The suggested redox interactions seem primarily to cause the reversible
      BL modulation.

PMID- 14974723
TI  - Calcium is involved in photomovement of cyanobacterium Synechocystis sp. PCC
      6803.
AB  - The unicellular cyanobacterium Synechocystis sp. PCC 6803 (Syn6803) exhibits
      photomovement through gliding motility. For a better understanding of
      photomovement in Syn6803, we examined the effects of Ca2+ on photoorientation and
      motility using a computer-assisted videomicroscope motion analysis system. When
      calcium ion was chelated from the basic motility medium by adding 0.5 mM ethylene
      glycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), the
      photoorientation was completely inhibited, whereas the gliding motility remained
      approximately 70% of the control. Photoorientation impaired by EGTA was nearly
      recovered within 30 min upon addition of 1 mM Ca2+. The recovery of
      photoorientation by Ca2+ was mimicked by either Mn2+ or Mg2+ but not by Ba2+ or
      Sr2+. Lanthanum ion at 10 microM completely inhibited both phototactic
      orientation and gliding motility of Syn6803. Furthermore, pimozide (voltage-gated
      L-type calcium channel inhibitor), orthovanadate (calcium efflux blocker) and
      A23187 (calcium ionophore) partially inhibited phototactic orientation and
      gliding motility. Interestingly, photoorientation was prevented with increasing
      concentrations of calmodulin antagonist such as trifluoperazine (TFP) and
      chlorpromazine, but gliding motility was inhibited in proportion to the
      concentration of TFP. The results we present strongly indicate that Ca2+ plays a
      significant role in regulating the photomovement of Syn6803.

PMID- 14974725
TI  - Effects of different quantities of fat on serum and liver lipids, phospholipid
      class distribution and fatty acid composition in alcohol-treated rats.
AB  - The present study investigated the quantitative effect of dietary fats and
      ingestion of alcohol on serum and liver lipids, fatty acid bound to phospholipids
      and their class distribution of male Wistar rats. The rats in C (control) and A
      (alcohol) groups were fed a standard laboratory diet, HFC (high fat-control) and
      HFA (high fat-alcohol) groups were fed a high fat diet (standard diet
      supplemented with 20 g%w/w, sunflower oil: lard mixture 1: 1) for 6 wk. Alcohol
      treated rats consumed alcohol at the rate of 9 g/kgbw/d (15-20% energy). Liver
      phospholipid (PL) content was decreased, and phospholipid/cholesterol liver molar
      ratio increased in the alcohol treated rats. The proportion of serum
      sphingophospholipid (Sph) was significantly lower and proportion of
      phosphatidylcholin (PC) significantly higher in serum PL in alcohol-treated rats.
      Phospholipid class distribution was unaffected by alcohol feeding in liver.
      Significantly lower levels of 16:1n-7 and higher levels of 20:5n-3 and 22:4n-6 in
      the serum PL were observed in the alcohol-treated rats. The groups on the HF diet
      increased levels of 20:4n-6, 22:4n-6 and total n-6, polyunsaturated fatty acid
      (PUFA) and decreased levels of 18:1n-9 and total monounsaturated fatty acids
      (MUFA)in both liver and serum PL, but n-3 fatty acid increased in serum PL and
      decreased in liver PL compared to groups on the standard diet. Alcohol fat
      interaction was evident in MUFA and PUFA/SFA in serum PL and n-6, MUFA, PUFA and
      polyunsaturated/saturated fatty acid ratios (PUFA/SFA) in liver PL. This study
      showed that the high fat intake in alcohol-treated rats increased levels of 20:4n
      6, 22:4n-6 and 20:4/18:2 ratio, and decreased level of 18:1n-9 in liver and serum
      phospholipids.

PMID- 14974726
TI  - Decreased blood levels of lactic acid and urinary excretion of 3-methylhistidine
      after exercise by chronic taurine treatment in rats.
AB  - Taurine is reported to increase contractility of skeletal muscle and cardiac
      myocyte, which can increase exercise performance. The present study aimed to
      clarify taurine's effect on chronic endurance exercise, especially accumulation
      of lactic acid (LA), a marker of fatigue and ability of aerobic exercise, and
      urinary secretion of 3-methylhistidine (3-MH), a marker of muscle breakdown in
      rats. After exercise blood levels of LA and urinary excretion of 3-MH were
      significantly increased and this increase was significantly less in those with
      chronic treatment of taurine. Taurine treatment also significantly decreased fat
      accumulation and blood levels of cholesterol and triglyceride, which might
      improve insulin resistance and utilization of fat and glucose. These results
      indicate taurine treatment is useful for reducing physical fatigue and muscle
      damage during exercise training in rats, presumably due to antioxidant property
      and improvement of muscle and cardiac functions by taurine.

PMID- 14974727
TI  - Barley beta-glucan lowers serum cholesterol based on the up-regulation of
      cholesterol 7alpha-hydroxylase activity and mRNA abundance in cholesterol-fed
      rats.
AB  - Barley, which is high in soluble dietary fiber (particularly beta-glucan), is
      thought to have hypocholesterolemic effects. The present study was performed to
      further elucidate the hypocholesterolemic actions of waxy barley, and the extent
      to which they can be attributed to beta-glucan. Male Sprague-Dawley rats (n=21)
      were fed control (fiber-free) diets, diets with the addition of 2.5%, refined
      beta-glucan or 30% waxy barley that provides approximately 2.5% beta-glucan in
      the diet for 2 wk. Body weight gain and food efficiency of rats were unaffected
      by diet. beta-glucan or waxy barley decreased serum levels of total cholesterol
      (p < 0.05) by 13.5% or 18.9%, and also decreased LDL-cholesterol 19.4% or 24.3%,
      respectively. Addition of refined beta-glucan or waxy barley to the diet resulted
      in greater bile acid excretions (p < 0.05) compared to the control group. The
      waxy barley diet up-regulated by 2. 3 times and the beta-glucan diet by 1.5 times
      the activity of cholesterol 7a-hydroxylase (CYP7A1). Hepatic CYP7A1 mRNA level
      paralleled the increases in enzyme activity. The results of this study suggest
      that the hypocholesterolemic effects of both beta-glucan and a waxy barley diet
      may be due to the enhancement of CYP7A1 expression resulting from increased fecal
      excretion of bile acids.

PMID- 14974728
TI  - The effects of nutrients in improving the depression of gonadal development in
      growing male rats kept under disturbed daily rhythm--investigations based on the
      L8(2(7)) type orthogonal array--.
AB  - The purpose of this experiment was to clarify the effects of nutrients on the
      gonadal development of male rats kept under constant darkness as a model of
      disturbed daily rhythm. Protein, methionine, vitamins, minerals and fat were
      selected as experimental factors, and eight kinds of diets were prepared based on
      the L8(2(7)) type orthogonal array. Dietary contents of the nutrients were normal
      (AIN-76 diet) or 1/3 to 1/2 of the normal content. Four-week-old rats (Fischer
      344 strain) were kept under constant darkness for 4 wk. Control groups were kept
      under 12-h light/dark cycle. After 4 wk, the gonadal weights and serum
      testosterone content were evaluated. The effects of nutrients on gonadal
      development in rats differed between constant darkness groups (D-groups) and
      normal lighting groups (N-groups). Among the D-groups, the highest value for
      testes weight was observed under the normal protein, methionine added, low
      vitamin, low mineral and normal fat diet. The lowest value for testes weight was
      observed under the low protein, methionine added, normal vitamin, normal mineral
      and low fat diet. Among the N-groups, the highest value for testes weight was
      observed under the normal protein and no methionine diet, and the lowest value
      was observed under the low protein and no methionine diet. Among the D-groups,
      the highest value for serum testosterone was observed under the normal protein
      and low mineral diet. In the N-groups, serum testosterone was not affected by
      nutritional factors. It became clear that the amounts of protein, methionine,
      vitamins, minerals, and oil which are necessary for the gonadal development of
      growing male rats change when kept in constant darkness.

PMID- 14974729
TI  - The relationship between serum selenium levels and lipid profiles in adult women.
AB  - Low selenium status draws much attention because of the possible involvement in
      the etiology of cardiovascular disease (CVD). Hyperlipidmia or dyslipidemia, a
      very important risk factor for CVD, occurs frequently in middle-aged Koreans.
      While selenium deficiency is supposed to aggravate blood lipid profiles, it has
      been shown that selenium status diminishes with advanced age. However, little is
      known about the selenium status of Koreans, its age-related change, and its
      relationship to blood lipid levels. In this study the serum selenium level of
      females according to age and its association with blood lipid profiles were
      examined. Serum selenium concentration was determined by the instrumental neutron
      activation analysis method (INAA) using the HANARO research reactor. The overall
      proportion of women having selenium deficiency, with less than 80.0 microg/L of
      the selenium concentrations in the serum, was 18.3%. The serum selenium levels in
      the young-adult. middle-aged and elderly groups were 120.6 microg/L, 97.2
      microg/L, and 90.8 microg/L, respectively. Biochemical indices derived from serum
      selenium levels showed that subjects with the lowest tertile of selenium
      concentration had significantly higher atherogenic index and lower HDL
      cholesterol levels compared to those with the highest tertile. However, only the
      serum HDL-cholesterol level showed the dependency on the selenium status as
      determined by step-wise analysis in the subjects below the age of 40. It was
      noted that in the subjects over the age of 40 (pooled middle-aged and elderly),
      any dependency of serum lipid profiles on the selenium status was not observed.
      The results of this study indicated that there is a decreasing tendency of
      selenium levels with age and that selenium status is associated with blood lipid
      levels only in young-adult females.

PMID- 14974730
TI  - Zinc in oysters (Crassostrea gigas): chemical characteristics and action during
      in vitro digestion.
AB  - To obtain information on the luminal absorption of oyster zinc, the zinc action
      during an in vitro protease digestion of oysters was examined. More than 90% of
      the zinc rendered solute at pH 1.3 or 3.0 irrespective of the pepsin digestion.
      The solute zinc was partially re-precipitated by neutralization, and trypsin
      digestion did not render the re-precipitated zinc solute. When the pepsin
      digestion was performed at pH 5.0, the ratio of soluble zinc in trypsin digest
      decreased. When the trypsin digest was fractionated by Sephadex G-25 , the zinc
      was eluted later than the peptide fragments. These results indicate that the pH
      of the stomach juice rather than peptides released by the digestion of oyster
      protein highly contributes to the oyster zinc in the small intestine becoming
      solute.

PMID- 14974731
TI  - Alum augments the experimental allergenicity of Kunitz-type soybean trypsin
      inhibitor independent of the antigen-adsorption.
AB  - In order to inspect the significance of the adsorbing property in the adjuvant
      activity to enhance IgE production, we immunized BALB/c mice against Kunitz-type
      soybean trypsin inhibitor (KSTI), the most potent experimental allergen among
      soybean proteins, associated with Aluminum hydroxide (alum) or DEAE-Sephadex
      particles. The production of immunoglobulin isotypes was analyzed at the various
      amounts, 3-3,000 microg per mouse, of the antigen dosages. In our experiments,
      although alum did not adsorb KSTI significantly, it augmented the total and the
      antigen-specific IgE without affecting the optimal range of the antigen dosage.
      On the other hand, alum did not effectively enhance the production of the other
      immunoglobulin isotypes. The production of immunoglobulin isotypes other than IgE
      increased dose-dependently on the antigen. These results ensured our previous
      finding that another protein, ovalbumin, was used as the antigen. We also
      demonstrated that the adsorption of KSTI by DEAE-Sephadex in the immunizing
      vehicle resulted in the requirement of more KSTI for accomplishing the equal
      immunity in BALB/c mice compared to the control. Moreover, we demonstrated that,
      regardless of the inability to adsorb KSTI, alum exerted its adjuvant activity
      only when it was co-injected with the antigen. These results showed that some
      biochemical effect, other than adsorptive activity, to enhance the production of
      the antigen-specific IgE resides in alum.

PMID- 14974732
TI  - Stimulation of butyrate production in the large intestine of weaning piglets by
      dietary fructooligosaccharides and its influence on the histological variables of
      the large intestinal mucosa.
AB  - Fructooligosaccharides (FOS) reach the large intestine and are fermented into
      short-chain fatty acids (SCFA), lactate, and carbon dioxide. As the major energy
      source for the epithelial cells of the large intestine, n-butyrate stimulates the
      proliferation of cells as well as mineral and water absorption from the lumen. We
      examined the effect of dietary FOS supplementation on luminal SCFA production and
      its influence on the morphometrical variables of mucosa of the large intestine in
      commercially available pigs. Six weaning piglets were used. After 7 d of
      adaptation, three pigs were given a test diet containing FOS (10%) ad libitum for
      10 d. The other three remained on the basal diet and were used as controls. At
      the end of the experiment, their large intestines were removed, and the cecum,
      gyri centripetales, gyri centrifugales, and rectum were separated. The contents
      of each portion were collected and measured for SCFA concentration, pH, and
      moisture. A micrometer was used to measure the crypt depth. The numbers of
      epithelial and mitotic cells in the crypt columns were also counted. The
      concentration of SCFA was significantly higher in piglets fed FOS than in the
      controls. The concentration of n-butyrate was markedly stimulated by FOS. The
      number of epithelial. mitotic, and mucin-containing cells was higher in piglets
      fed FOS than in the controls. Accordingly, the crypt depth was larger in the FOS
      fed piglets. The luminal n-butyrate concentration showed a significantly positive
      correlation with the crypt depth and the number of epithelial, mitotic, and mucin
      containing cells.

PMID- 14974733
TI  - Evidence suggesting that difructose anhydride III is an indigestible and low
      fermentable sugar during the early stages after ingestion in humans.
AB  - We investigated the influences of difructose anhydride III (DFAIII), a novel
      commercially available disaccharide, on sugar metabolism, breath hydrogen and
      serum acetate in the early stages after ingestion to determine whether DFAIII is
      an indigestible sugar and to what degree it is fermentable in humans. This study
      was designed as a randomized controlled single-blind crossover test with 9
      healthy subjects, who drink a 200 mL water solution containing 10 g of DFAIII,
      lactulose or sucrose following overnight fasting. Blood samples (for analysis of
      glucose, fructose, insulin, triacylglycerol, free fatty acids, and acetate) were
      collected at 0, 0.5, 1, 2, 4, 8 h after the ingestion and breath samples (for
      analysis of hydrogen and methane gases) were collected at 1 h intervals until 8 h
      after the ingestion. We also interviewed each subject hourly about the incidence
      and severity of specific abdominal complaints and other symptoms. The results
      revealed that ingestion of 10 g of DFAIII did not change the serum levels of
      glucose, fructose, and insulin, similarly to the case with lactulose, and no
      increase in breath hydrogen excretion was comparable to the case with sucrose.
      The incidence of specific abdominal symptoms tended to be lower after DFAIII
      ingestion than after lactulose ingestion. It thus turned out that DFAIII was
      indigestible and low fermentable in the early stages after ingestion.

PMID- 14974734
TI  - Bitter melon malt vinegar increases daily energy turnover in rats.
AB  - Vinegar is generally believed to be good for health. A mash consisting of 35%
      ethanolic extract from bitter melon malt vinegar-water (8:50:42) was subjected to
      further acetate fermentation and the resulting vinegar was converted to dried
      vinegar powder by spray drying after adsorption on dextrin, which was mixed with
      a commercial rat chow (CRF-1) in the ratio of 1:19 so as to prepare an
      experimental diet. Male 12-wk old rats of LETO and OLETF strains were fed this
      experimental diet in parallel with CRF-1 (control) and examined for respiratory
      quotient (RQ) and blood or plasma parameters associated with diabetes mellitus.
      Administration of the experimental diet increased daily food intake as well as
      daily energy expenditure in both strains. RQ significantly lessened in the
      vinegar diet-fed group of LETO strain, which was reflected not only in the
      increased energy consumption from fat but also in the decreased energy
      consumption from carbohydrate, while no significant difference was observed
      between both dietary groups of OLETF strain in this respect. The profiles of
      diurnal energy expenditure in both dietary groups of LETO strain exerted two
      peaks before lights-on and lights-off. Nevertheless, there was a clear difference
      between both dietary groups of OLETF strain: interestingly the reproduction of
      the two peaks became conspicuous in the vinegar diet-fed group despite the lack
      of such peaks in the control. As a consequence of blood or plasma inspection, it
      turned out that there was no change in HbA1c but a significant increase in plasma
      cholesterol in the vinegar diet-fed OLETF rats. From these results, a long-term
      administration of bitter melon malt vinegar can be expected to suppress a
      lowering of energy turnover inherent with aging and thereby improve anorexia
      rather than to bring about a preventive effect against the manifestation of
      NIDDM.

PMID- 14974735
TI  - Synthesis and antioxidative activity of 6-hydroxypyridoxine.
AB  - An attempt to synthesize 6-hydroxypyridoxine (OPN), hydroxylation on C-6 of
      pyridoxine (PN) by hydroxyl radical (OH*). was conducted. Application of two well
      known OH* generating reactions, i.e. the Fenton reaction and the Fe2+
      EDTA/ascorbate reaction, were unsuccessful, as large amounts of by-products were
      formed. Although generation of OH* by autoxidation of ascorbic acid in the
      absence of metal ions was slow, by-products were formed in small quantities, and
      OPN was easily obtained in colorless crystals. Its structure was confirmed by
      spectral analyses. OPN was comparable to polyphenols such as (+)-catechin, rutin
      and gallic acid in the antioxidative activity against linoleic acid peroxidation,
      and was an effective DPPH radical scavenger, though the DPPH radical-scavenging
      activity of OPN was somewhat lower than that of the polyphenols. PN was
      relatively inactive under the conditions used here, indicating that the
      introduction of a hydroxyl group on C-6 of PN greatly enhanced both activities.

PMID- 14974736
TI  - Clinical study on the combined effect of capsaicin, green tea extract and essence
      of chicken on body fat content in human subjects.
AB  - This study was conducted to assess the body fat content of free-living healthy
      human subjects taking a health supplement containing 0.4 mg capsaicin, 625 mg
      green tea extract (125 mg catechins and 50 mg caffeine) and 800 mg essence of
      chicken (CGTE). Subjects were advised to maintain their regular dietary habits
      and routine physical activity throughout study duration. Their body fat content
      was measured before and throughout the trial duration using a hand-grip body fat
      monitor. After 2 wk of supplementation with CGTE, the mean body fat percentage of
      males and female subjects was significantly less than the initial value (p <
      0.05; t-test). 70.6%, of volunteers showed a trend for decreasing body fat
      content with 4 subjects showing a significant decrease in body fat content over
      time. The findings suggested that the effects were more prominent in subjects
      with higher initial body fat content. It was also demonstrated that the resting
      energy expenditure (REE) of the subjects taking the test samples were
      significantly increased in groups supplemented with CGTE, compared to placebo
      group. Thus, the combined thermogenic effect of capsaicin, green tea extract and
      essence of chicken could translate to a positive clinical effect by reducing
      approximately 460 g of body fat, following 2 wk of supplementation and the
      application of this natural health supplement for excess fat regulation, should
      be considered.

PMID- 14974737
TI  - Effects of sesamin and capsaicin on the mRNA expressions of delta6 and delta5
      desaturases in rat primary cultured hepatocytes.
AB  - Sesamin, a lignan in sesame seeds and sesame seed oil, and capsaicin, the pungent
      principle of hot red pepper, affect lipid metabolism. Sesamin specifically
      inhibits delta5 desaturase activity in the Mortierella alpina fungus and rat
      liver microsomes, however, the effects of sesamin and capsaicin on mRNA
      expressions of delta6 and delta5 desaturases are not still clear. In this study,
      we investigated the effects of sesamin and capsaicin on the desaturation indexes
      of delta6 [(gamma-linolenic acid+dihomo-gamma-linolenic acid)/linolenic acid,
      (GLA+DGLA)/LA] and delta5 (arachidonic acid/DGLA, AA/DGLA) and mRNA expressions
      of delta6 and delta5 desaturases in rat primary cultured hepatocytes. To measure
      the mRNA expressions of delta6 and delta5 desaturase, hepatocytes were cultured
      in the presence of sesamin or capsaicin for 24 h. To investigate the delta6 or
      delta5 desaturation index, hepatocytes were cultured in the presence of LA or
      DGLA, respectively, with sesamin or capsaicin for 24 h. The fatty acid
      composition of the cells was measured by GLC. The mRNA expressions of delta6 and
      delta5 desaturases were detected by real time quantitative RT-PCR. Sesamin and
      capsaicin had no effect on the mRNA expressions of delta6 and delta5 desaturases
      in rat hepatocytes. Capsaicin had no effect on both delta6 and delta5
      desaturation indexes, either. On the other hand, sesamin significantly reduced
      the index of delta5 desaturation but not delta6 desaturation. These results
      suggested that sesamin reduced the delta5 desaturation index without the changing
      of the delta5 desaturase mRNA level.

PMID- 14974738
TI  - Glucosyl hesperidin improves serum cholesterol composition and inhibits
      hypertrophy in vasculature.
AB  - Long-term administration of hesperidin (HES) or glucosyl hesperidin (GHES), a
      water-soluble analogue of HES, brings about an antihypertensive effect on
      spontaneously hypertensive rats (SHR). In the present study, we investigated the
      effects of long-term administration of HES and GHES (corresponding to 30 mg/d/kg
      body weight) on serum lipid concentration and morphology of vasculature. Serum
      HDL cholesterol increased in both SHR and Wistar-Kyoto rats (WKY) fed a HES- or
      GHES-containing diet for 25 wk. Simultaneously, GHES administration reduced the
      vascular diameter and media-intimal cross-sectional area of the abdominal aorta
      in SHR. These results suggest that HES as well as GHES improves serum cholesterol
      composition and that GHES inhibits hypertrophy in vasculature as well.

PMID- 14974739
TI  - Antioxidative activity and protective effect against ethanol-induced gastric
      mucosal damage of a potato protein hydrolysate.
AB  - Antioxidative activity and protective effect against ethanol-induced gastric
      mucosal damage of potato protein hydrolysate (potato peptides, Po-P) were studied
      in vitro and in vivo. The Po-P obtained by proteolysis with Amano P and
      pancreatin inhibited linoleic acid oxidation either by 83%, at its coexistent
      0.005% in a ferric thiocyanate assay system or by 32% at its coexistent 0.0002%
      in a beta-carotene decolorization assay system. Meanwhile Po-P were orally
      administered to male Wistar rats at doses of 12.5-100 mg/kg of body weight (BW)
      30 min prior to ethanol injection. Consequently the ethanol-induced gastric
      damage was significantly reduced in a dose-dependent manner in the Po-P
      administered rat. The highest effect was observed in the group dosed with 100 mg
      Po-P/kg BW; the inhibition ratio was 69.6%. The extent of antioxidation or
      protection against ethanol-induced gastritis was quite similar to those of the
      respective peptides from casein, corn protein and ovalbumin, suggesting that the
      potato protein hydrolysate could serve as a useful food ingredient in practical
      eating habits.

PMID- 14974740
TI  - The burden and impact of COPD in Asia and Africa.
AB  - Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and
      mortality worldwide. The World Health Organization (WHO) estimated that COPD is
      currently the seventh leading cause of death and disability worldwide, but will
      rise to the fifth position by 2020. The estimated prevalence of COPD worldwide in
      2001 was 1013/100,000 population; it was highest in the Western Pacific Region
      and lowest in Africa. The mortality from COPD followed the same pattern. The
      prevalence of smoking is slowly decreasing in the industrialised world and rising
      in developing countries, especially in Asia and Africa. Cigarette consumption per
      adult has also decreased in the Americas, remained the same in Europe but
      increased in all other regions, especially the Western Pacific. Indoor air
      pollution from combustion of biomass/traditional fuels and coal, previous
      tuberculous infection, outdoor air pollution and childhood respiratory infections
      are other important risk factors for COPD in developing countries. The rise in
      morbidity and mortality from COPD will be most dramatic in Asian and African
      countries over the next two decades, mostly due to progressive increase in the
      prevalence of smoking. As developing countries can ill afford the added economic
      burden of COPD and other smoking-related diseases, there is an urgent need for
      multi-dimensional actions in reducing the main risk factor of cigarette smoking.

PMID- 14974741
TI  - Study of resistance to anti-tuberculosis drugs in five districts of Equatorial
      Guinea: rates, risk factors, genotyping of gene mutations and molecular
      epidemiology.
AB  - SETTING: Five districts in Equatorial Guinea, March 1999 to February 2001.
      OBJECTIVES: To determine tuberculosis drug resistance among new and previously
      treated cases, the risk factors associated with resistance, and the mutations
      associated with isoniazid and rifampicin (katG, inhA and rpoB genes) resistance,
      and to genotype resistant strains. RESULTS: A positive culture identified as
      Mycobacterium tuberculosis complex was obtained in 240/499 patients.
      Susceptibility testing was performed in 236 strains. The overall resistance rate
      in new cases was 16.9% compared to 41.6% in previously treated cases. Isoniazid
      resistance was the most frequent (respectively 12.5% and 16.6%) in the two
      groups, while multidrug resistance was observed in 1.7% and 25% of new and
      previously treated cases, respectively. Female sex was statistically associated
      with resistance in new cases. Of 41 isoniazid-resistant strains, 33 (80.5%) had
      mutations in the inhA gene; none had mutations in the katG gene and eight had no
      mutations in either gene. All strains had low-level isoniazid resistance. Of
      eight strains resistant to rifampicin, six had mutations in the rpoB gene.
      Genotyping defined seven clusters. CONCLUSIONS: Moderate resistance was found in
      new cases. Low-level isoniazid resistance predominated among mutations in the
      inhA gene, with a high percentage of clustering in resistant strains.

PMID- 14974742
TI  - Drug resistance monitoring: combined rates may be the best indicator of programme
      performance.
AB  - SETTING: Greater Mymensingh District, Bangladesh. OBJECTIVES: To determine
      changes in prevalence of drug resistance of Mycobacterium tuberculosis under
      DOTS. DESIGN: Drug susceptibility testing of systematic samples of M.
      tuberculosis isolated from all sputum smear-positive cases newly registered in
      sentinel centres during 1995 and 2001. Continuous monitoring of retreatment
      registrations and resistance of strains from relapse and failure cases. RESULTS:
      Of 942 strains from the new cases in 2001, 10.8% showed resistance to any drug,
      6.2% to isoniazid, 0.4% to rifampicin (all of them multidrug-resistant, MDR),
      7.1% to streptomycin, and 1.0% to ethambutol. Corresponding rates for 99 strains
      from previously treated cases were 32%, 20%, 3%, 20% and 2%, respectively.
      Although most rates of resistance had decreased since 1995, increased
      streptomycin resistance was the only significant change when new and previously
      treated cases were considered separately. However, combined resistance for any
      drug, isoniazid, rifampicin and MDR had decreased significantly. CONCLUSION: As
      suggested by monitoring of resistance in failure and relapse cases and by routine
      programme reports, drug resistance had decreased. Combined resistance
      demonstrated changes between periodic surveys better than its subgroups, and may
      be a more reliable and comprehensive indicator. However, continuous monitoring of
      the pool of resistant retreatment cases is a more efficient strategy.

PMID- 14974743
TI  - Development of acquired drug resistance in recurrent tuberculosis patients with
      various previous treatment outcomes.
AB  - SETTING: Chiang Rai province, Northern Thailand. OBJECTIVE: To study the
      probability of acquiring drug resistance to isoniazid (H) and rifampicin (R) on
      recurrence after treatment success, default and failure, among sputum smear
      positive pulmonary tuberculosis (TB) patients treated with standardised short
      course chemotherapy. DESIGN: Retrospective analysis of registration records of TB
      patients from May 1996 to December 2000 in Chiang Rai, where routine drug
      susceptibility testing (DST) is conducted for surveillance purposes. Patients
      registered twice or more were examined. RESULTS: Of 59 cases treated with HRZE/HR
      who underwent DST at the time of registration, 31 were fully susceptible to H and
      R at first registration, of whom four acquired drug resistance to H or R. Of 13
      cases resistant to H or R at first registration, 11 became multidrug-resistant
      (MDR). The remaining 15 patients were original MDR cases. Among 28 MDR or H- or R
      resistant cases, six reverted from resistant to susceptible. DISCUSSION: A high
      proportion of patients with H- or R-resistant TB became MDR after treatment with
      2HRZE/HR. Using this regimen, MDR may increase in a population with a high
      prevalence of H or R resistance. We are unable to explain why some drug-resistant
      cases became drug-susceptible. Further investigation is necessary.

PMID- 14974744
TI  - Molecular epidemiology of tuberculosis in the north Hokkaido district of Japan.
AB  - SETTING: The incidence of tuberculosis in Japan has fallen rapidly in the past 50
      years, to 27.9 cases per 100,000 population in 2001. OBJECTIVE: To assess the
      molecular epidemiology of tuberculosis in the north Hokkaido district, Japan.
      DESIGN: Restriction fragment length polymorphism analysis was consecutively
      performed on Mycobacterium tuberculosis strains from patients with pulmonary
      tuberculosis from April 1999 to March 2002. RESULTS: Of 229 patients, strains
      from 227 (99.1%) were available for analysis. The mean age of the patients
      analysed was 69.4 years. There was one immigrant patient. Two hundred and seven
      patients had six or more copies of IS6110. Of these, 16 (7.7%) in eight clusters
      had identical patterns, 120 (58.0%) belonged to five groups that had similar
      patterns (Dice coefficient >0.7) and 80 (38.6%) belonged to the 35 groups with
      the most common patterns (Dice coefficient >0.9). CONCLUSION: These results may
      reflect the epidemiological characteristics, age and migration of the residents
      and the incidence of tuberculosis of the area, and also those of Japan: many
      elderly patients were infected in the past, when the incidence of tuberculosis
      was very high.

PMID- 14974745
TI  - Tuberculin reactivity and tuberculosis epidemiology in the Pakaanova (Wari')
      Indians of Rondonia, south-western Brazilian Amazon.
AB  - OBJECTIVE: To investigate the characteristics of tuberculin skin test reactivity
      in the Pakaanova Indians, in Amazonia, Brazil, after revaccination of all study
      participants with bacille Calmette-Guerin (BCG). METHODS: The investigation was
      designed as a post-BCG vaccination purified protein derivative (PPD) survey. Data
      included PPD readings, age, sex, nutritional status, place of residence, previous
      tuberculosis, physical examinations and BCG status. Bivariate and multivariate
      logistic regression analyses were conducted. RESULTS: About 90% (n = 505) of the
      total population participated. One third (32.1%) of the subjects presented
      induration > or = 10 mm at 72 h. Induration sizes showed weak linear correlation
      with age; differences between sexes were not observed. Skin reaction was not
      associated with nutritional status. Individuals with a history of tuberculosis
      were six times more likely to test positive. History of tuberculosis, age, and
      previous BCG vaccination were significantly associated with PPD reactivity in the
      multivariate analyses. CONCLUSION: The Pakaanova showed a high proportion (58.4%)
      of non-reactors, even with a recent BCG booster. Sex differences in PPD
      reactivity were either not present or could not be demonstrated. The association
      between age and PPD reactivity resembles that observed in other Amazonian
      populations. The authors discuss the potential of PPD testing as a screening tool
      to enhance tuberculosis detection, especially in indigenous populations in
      Amazonia with limited access to health services.

PMID- 14974746
TI  - Identifying early treatment failure on category I therapy for pulmonary
      tuberculosis in Lima Ciudad, Peru.
AB  - SETTING: Ambulatory, public tuberculosis treatment facilities, central Lima,
      Peru. OBJECTIVE: To identify risk factors for failure on directly observed
      Category I therapy. DESIGN: Case-control study. All failures of Category I
      (2HREZ/4H2R2) therapy in 2000 (2.9% of smear-positive TB patients) were included
      as cases; two controls per case were matched on health center and approximate
      time of treatment initiation. RESULTS: The study included 38 cases and 76
      controls, all new smear-positive, pulmonary TB patients treated with Category I
      therapy in central Lima in 2000. Neither treatment irregularity nor incidence of
      adverse events predicted failure in the study group. Mean baseline body mass
      index was lower in cases than in controls (P = 0.06). Cases gained less weight
      during therapy (P = 0.01). Smear positivity at 2 months of therapy was strongly
      associated with failure (OR 11.7; 95%CI 2.4-57.5). No controls had positive
      smears at or after 3 months of therapy (OR [corrected] 144.9; 95%CI 8.4-2500).
      Nearly 75% of cases with isolates tested for susceptibility to first-line drugs
      had multidrug-resistant TB (MDR-TB). CONCLUSION: A large proportion of failures
      on Category I therapy can be identified early. As three-quarters of patients with
      susceptibility results have MDR-TB, early referral for culture and drug
      susceptibility testing is critical for prompt initiation of appropriate therapy
      and improved outcomes.

PMID- 14974747
TI  - Vertical transmission of Mycobacterium tuberculosis in KwaZulu Natal: impact of
      HIV-1 co-infection.
AB  - BACKGROUND: Increases in perinatal TB have paralleled the exacerbation of the TB
      epidemic in KwaZulu Natal. The exact risks for vertical transfer of Mycobacterium
      tuberculosis (VTRTB) to the baby are unknown, as is the impact of HIV-1 co
      infection, which frequently accompanies maternal TB disease in the region.
      DESIGN: Prospective case series study of 82 HIV-1-infected and 25 non-infected
      pregnant mothers, King Edward VIII Hospital, KwaZulu Natal, South Africa.
      RESULTS: Perinatal mortality in HIV-1/TB diseased mothers was 85/1000 and
      associated with maternal anaemia (P = 0.02); 46% of newborns were premature, 66%
      low birth weight and 49% intrauterine growth restricted. These were significantly
      higher than overall hospital rates (P < 0.01, OR 4.8, 95%CI 3.2-7.0). Sites of
      detection of maternal TB, distribution of bacteriologically-proven TB, obstetric
      comorbidity and perinatal morbidity were similar in HIV-1-infected and non
      infected mothers. VTRTB was detected in 16 newborns (16%), occurring similarly in
      bacteriologically-proven and suspected maternal TB disease, with no difference
      between HIV-1-infected and non-infected mothers. Eleven newborns with VTRTB were
      HIV-1 exposed; 64% acquired HIV-1 and died from rapidly progressive disease by 10
      months of age. HIV-1-infected mothers and their exposed newborns had
      significantly lower CD4 counts. No association between perinatal maternal viral
      load, CD4 count or VTRTB was detected. CONCLUSION: Mothers with TB disease in
      pregnancy are at risk for significant perinatal morbidity, mortality and VTRTB.

PMID- 14974748
TI  - A gender-focused qualitative study of barriers to accessing tuberculosis
      treatment in The Gambia, West Africa.
AB  - SETTING: The Medical Research Council unit in Fajara, The Gambia. OBJECTIVE: To
      explore gender differences in care seeking behaviour, access to treatment, and
      knowledge and perceptions about tuberculosis. DESIGN: Fifteen government health
      workers were interviewed to define the scope of the issues involved, then 15 male
      and 15 female tuberculosis patients were interviewed. Qualitative semi-structured
      questionnaires were used in health worker and patient interviews. Data were
      analysed using the thematic framework method. The main themes were compared
      between male and female patients. RESULTS: Patients often initially consulted
      traditional healers and pharmacies. Women used traditional healers more, probably
      because of stronger traditional beliefs, time constraints and increased
      confidentiality. Regardless of sex, most patients acknowledged problems affording
      the transport costs to access treatment. Health workers and patients highlighted
      negative perceptions of tuberculosis. Lack of knowledge about tuberculosis and
      stigma were widely reported, and were worst in female patients. CONCLUSIONS:
      Tuberculosis is a stigmatised disease in The Gambia, particularly in women, and
      its management is associated with access problems. Health education is required
      to provide basic knowledge about the disease and to reduce stigma, and further
      decentralisation of tuberculosis services is needed to improve access.

PMID- 14974749
TI  - Cultural case management of latent tuberculosis infection.
AB  - SETTING: The proportion of tuberculosis (TB) among foreign-born individuals in
      the United States is steadily increasing. Treatment of latent TB infection can
      prevent future cases of disease, although generally only 60% of patients who
      start a 6-month regimen of isoniazid complete therapy. OBJECTIVE: Cultural case
      management--employing case manager cultural mediators who serve patient-defined
      needs in addition to performing TB control functions--may improve results of
      testing and treatment in one high-risk group, new refugees. DESIGN: A cultural
      case management approach was established for finding and treating latent TB
      infection among three groups of new refugees: from the former Soviet Union (FSU),
      former Yugoslavia (FY), and Somalia. RESULTS: From July 1999 through December
      2000, treatment was offered to 442 refugees, of whom 389 (88%) started and 319
      (82%) completed therapy. The completion rate among starters from the FSU was 76%,
      for those from FY it was 94% and for those from Somalia it was 88%. Among all
      refugees to whom treatment was offered, 319/442 (72%) completed therapy.
      CONCLUSION: Cultural case management may be a useful tool for expanding treatment
      of latent TB infection among foreign-born individuals.

PMID- 14974750
TI  - Can the poor adhere? Incentives for adherence to TB prevention in homeless
      adults.
AB  - SETTING: Community-based population of homeless adults living in San Francisco,
      California. OBJECTIVE: To compare the effect of cash and non-cash incentives on
      1) adherence to treatment for latent tuberculosis infection, and 2) length of
      time needed to look for participants who missed their dose of medications.
      DESIGN: Prospective, randomized clinical trial comparing a 5 dollar cash or a 5
      dollar non-cash incentive. All participants received directly observed preventive
      therapy and standardized follow-up per a predetermined protocol. Completion rates
      and amount of time needed to follow up participants was measured. RESULTS: Of the
      119 participants, 102 (86%) completed therapy. There was no difference between
      the cash and non-cash arms. Completion was significantly higher among males (OR
      5.65, 95%CI 1.36-23.40, P = 0.02) and persons in stable housing at study entry
      (OR 4.86, 95%CI 1.32-17.94, P = 0.02). No substance use or mental health measures
      were associated with completion. Participants in the cash arm needed
      significantly less follow-up to complete therapy compared to the non-cash arm (P
      = 0.03). In multivariate analysis, non-cash incentive, use of crack cocaine, and
      no prior preventive therapy were associated with more follow-up time. CONCLUSION:
      Simple, low cost incentives can be used to improve adherence to TB preventive
      therapy in indigent adults.

PMID- 14974751
TI  - Tuberculosis in patients with end-stage renal disease.
AB  - OBJECTIVE: To elucidate the clinical manifestations and risk factors of the
      mortality rate in uraemic patients with tuberculosis (TB) infection. DESIGN: We
      retrospectively analysed 62 patients with uraemia and active tuberculosis who
      were admitted to our hospital from 1990 through 2000. The patients were followed
      up for 2 years after discharge or until death. RESULTS: There were 43 men and 19
      women, with a mean age of 63 +/- 13 years. Extra-pulmonary TB was noted in 51.6%.
      The peritoneum and pleura were the two most common organs involved. Fever of
      unknown origin was the most common manifestation (77.4%). The corrected serum
      Ca2+ level of the patients was >10.5 mg/dl in 46.8%. C-reactive protein >6 mg/dl
      and leukocytosis (white blood cell count >10,000/mm3) at presentation were noted
      in more than half of the patients. A reversed serum albumin/globulin ratio and
      leukocytosis were found to be associated with mortality rate. CONCLUSION: More
      than half of the TB infections in patients with end-stage renal disease presented
      with extra-pulmonary involvement. Fever of unknown origin, reversed serum
      albumin/globulin ratio, and unexplained hypercalcaemia in maintenance dialysis
      patients suggested the possibility of tuberculosis.

PMID- 14974752
TI  - B-lymphocytes and co-stimulatory molecules in Mycobacterium tuberculosis
      infection.
AB  - SETTING: The immunological mechanisms that lead to the control of Mycobacterium
      tuberculosis infection are not well known. OBJECTIVE: To study the role of
      lymphocyte subsets and co-stimulatory molecules in M. tuberculosis infection.
      DESIGN: In 35 patients with pulmonary tuberculosis (PTB) and their contacts, 29
      persons with tuberculin skin test conversion (TSTC) and 20 healthy individuals
      with negative tuberculin skin test (NTST), we studied T-lymphocyte subsets (CD3,
      CD4, CD8, alphabetaTCR and gammadeltaTCR), B-cells, monocytes and co-stimulatory
      molecules CD28 and CD86 in peripheral blood. The results were analysed at
      univariate and multivariate level through discriminant analysis. RESULTS: At
      univariate level, compared with TSTC and NTST, PTB patients presented a decrease
      in CD4+ T-cells (P = 0.002), and B-cells (P = 0.02 and 0.001, respectively). With
      regard to NTST subjects, PTB patients also showed a decrease in the percentage of
      CD86+ monocytes (P = 0.02) and an increase in the percentage of CD86+ B
      lymphocytes (P = 0.02). At multivariate level, CD4+ T-lymphocytes showed
      statistical differences between PTB and TSTC subjects (P = 0.001). B-lymphocytes
      were discriminant between PTB and NTST (P < 0.001) and between TSTC and NTST
      individuals (P = 0.01). CONCLUSION: The number of total CD4+ T-cells is the best
      discriminant parameter for distinguishing between disease and infection, whereas
      the B-cell count is the best between healthy and infected individuals.

PMID- 14974753
TI  - Prospective evaluation of in-house polymerase chain reaction for diagnosis of
      mycobacterial diseases in patients with HIV infection and lung infiltrates.
AB  - SETTING: Rapid diagnosis of tuberculosis (TB) in AIDS is critical for optimal
      treatment to reduce mycobacterial dissemination, HIV-1 replication and mortality.
      The inadequate sensitivity of Ziehl-Neelsen staining and its inability to
      distinguish atypical mycobacteria delays accurate diagnosis. OBJECTIVE: To
      evaluate the polymerase chain reaction (PCR) for diagnosis of TB in
      bronchoalveolar lavage (BAL), blood and extra-pulmonary samples from patients
      with AIDS and pulmonary infiltrates. DESIGN: Specimens from 103 HIV-1-infected
      patients were prospectively analysed using bacteriological methods and IS6110
      PCR. Smear-positive samples were also tested using 16S ribosomal-DNA-PCR to
      identify Mycobacterium avium complex (MAC) infections. Gold standard diagnosis
      relied on positive cultures or treatment outcome. RESULTS: Thirty-four patients
      exhibited TB, one TB and MAC and four MAC. The sensitivity of IS6110-PCR was 100%
      in smear-positive samples, 81.8% in smear-negative BAL, 66.7% in extra-pulmonary
      samples and 42.9% in blood. Its specificity was 97.1% in BAL and 100% in extra
      pulmonary and blood specimens. The 16S rDNA-PCR identified M. avium from all
      smear-positive samples that grew MAC. CONCLUSIONS: IS6110-PCR proved useful in
      evaluating episodes with probable clinical diagnosis of pulmonary or mixed TB and
      negative smears, whereas 16S rDNA-PCR would be helpful for prompt differential
      diagnosis of MAC in smear-positive specimens.

PMID- 14974754
TI  - Appropriateness of extending the intensive phase of treatment based on smear
      results.

PMID- 14974755
TI  - Global Partnership to Stop TB: a model of an effective public health partnership.
AB  - SETTING: The Global Partnership to Stop TB. OBJECTIVE: To describe the need for a
      partnership, its development, its aims and how it goes about its business.
      RESULT: The international health community finds itself working under new
      constraints and in the presence of new actors and opportunities, including
      globalisation, economic and cultural changes, lack of resources, and the need for
      intersectoral collaboration. The World Health Organization (WHO) declared
      tuberculosis a global emergency in 1993. However, political commitment to
      controlling the growing pandemic was lacking, and TB continued to exact its
      remorseless toll. The Global Partnership to Stop TB can be seen as the result of
      the development over the last century of progressively more powerful forms of
      international organisations against tuberculosis. An outline is given of the
      current Global Partnership to Stop TB, including its goals, its progress from
      values to achievements and how it functions through various bodies. CONCLUSION:
      The Partnership is potentially an effective model for other public health issues.
      As such, it can contribute to and catalyse a new era of international
      cooperation.

PMID- 14974756
TI  - The Global TB Drug Facility: innovative global procurement.
AB  - The Global TB Drug Facility (GDF) is a new initiative to increase access to high
      quality tuberculosis drugs. The GDF, a project of the Global Partnership to Stop
      TB, is managed by its secretariat, in the World Health Organization (WHO),
      Geneva. It aims to provide tuberculosis drugs to treat up to 11.6 million
      patients over the next 5 years and to assist countries to reach the WHO global TB
      control targets by 2005. The GDF was launched on 24 March 2001. Six rounds of
      applications have been completed, with 46 countries and non-governmental
      organisations (NGOs) approved for support. The GDF is not a traditional
      procurement mechanism. It has adopted an innovative approach to the supply of
      drugs, by linking demand for drugs to supply and monitoring, using partners to
      provide services, using product packaging to simplify drug management and linking
      grants to TB programme performance. This paper describes the GDF operational
      procedures and experience gained so far. Key achievements to date are also
      outlined, including the creation of a flexible supply system to meet differing
      programme needs, rapid establishment of procedures, reduction in TB drug prices-
      a catalyst for DOTS expansion in countries, standardisation of products, and
      collaboration with partners. The GDF is flexible enough to meet the needs of
      countries with a TB burden. The GDF experience could be used as an example for
      global procurement of drugs and commodities for other diseases, such as HIV/AIDS
      and malaria. In the future it is likely that the GDF will expand to include
      second-line drugs and diagnostic materials for TB and could assist other
      partnerships to develop similar mechanisms and facilities to meet country needs.

PMID- 14974757
TI  - DOTS expansion: will we reach the 2005 targets?
AB  - The global targets for tuberculosis control consist of detecting 70% of estimated
      infectious cases and curing 85% of these by 2005. Since the introduction of the
      DOTS strategy, DOTS geographical coverage has increased substantially and
      treatment success rates under DOTS are approaching the targets, standing at 82%
      in 2000. However, DOTS case detection, albeit increasing, is still relatively
      low, at 32% in 2001. This target may not be reached by 2005. The low case
      detection is unlikely to stem from overestimating the global number of TB cases
      which has been estimated on several occasions, but from TB cases not being
      detected or notified for various reasons. The population may have poor access to
      TB services, cases may not be suspected or correctly diagnosed, cases may not be
      notified, and/or public health programmes or the private sector may not be
      adequately linked to the National Tuberculosis Programmes. Since the global TB
      targets were set, progress has been made. Political commitment has increased,
      additional financial resources mobilised, access to anti-tuberculosis drugs
      augmented and planning and coordination improved. Constraints still remain, the
      most important related to human resource capacity. Although the issue is being
      tackled, many countries still suffer from a lack of trained health care
      professionals. Finally, new strategies have been developed to face the current
      challenges such as public-private mix, community TB care, social mobilisation,
      TB/HIV collaborative interventions and Practical Approach to Lung Health. The
      current efforts should be maintained and strengthened in order to approach these
      targets.

PMID- 14974758
TI  - Stop TB-Halte a la Tuberculose-Canada: engaging industrialised nations in the
      challenge to meet global targets.
AB  - The Stop TB Partnership has engaged the 22 high-burden countries in a drive
      toward the goal of finding 70% of cases and curing 85% by 2005. Traditional
      partners, aid agencies and governments of industrialised nations have joined the
      Partnership, but the broader range of civil society remains outside the
      discourse, risking disinterest on the part of the donor community. Stop TB-Halte
      a la Tuberculose-Canada was organised to engage new partners to support the
      Canadian government's commitment to the goal of reducing poverty and diseases of
      poverty, including tuberculosis, by 50% by 2010. The successes and challenges are
      explored, and the possibility raised that having a Stop TB movement in every
      country will ensure that support is sustained and goals of global tuberculosis
      control reached.

PMID- 14974759
TI  - Prospects for new TB vaccines: Stop TB Working Group on TB Vaccine Development.
AB  - Research towards the development of improved TB vaccines has reached an important
      turning point. A large number of vaccine candidates such as modified BCG,
      attenuated Mycobacterium tuberculosis and protein or DNA subunit vaccines,
      resulting from over a decade of work in experimental laboratory models, are now
      getting ready for clinical testing. The transition from laboratory to clinical
      trials has a wide range of strategic and technical implications. Facilities and
      funding need to be identified for the production of clinical vaccine lots, an
      issue that is difficult to tackle due to the live organisms in some of the new
      vaccine candidates; regulatory hurdles need to be overcome; protocols and trial
      sites need to be developed, for phase III clinical efficacy trials in particular.
      The Stop TB Working Group on TB Vaccine Development provides a global forum that
      brings laboratory and clinical researchers together with experts in tuberculosis
      control and representatives from commercial and non-profit funding agencies to
      address these issues and to facilitate progress towards the common goal of
      improved vaccination strategies for tuberculosis.

PMID- 14974760
TI  - The marriage of cancer control and advocacy.

PMID- 14974761
TI  - Cancer statistics, 2004.
AB  - Each year, the American Cancer Society estimates the number of new cancer cases
      and deaths expected in the United States in the current year and compiles the
      most recent data on cancer incidence, mortality, and survival rates based on
      incidence data from the National Cancer Institute and mortality data from the
      National Center for Health Statistics. Incidence and mortality rates are age
      standardized to the 2000 US standard million population. A total of 1,368,030 new
      cancer cases and 563,700 deaths are expected in the United States in 2004.
      Incidence rates stabilized among men from 1995 through 2000 but continued to
      increase among females by 0.4% per year from 1987 through 2000. Mortality rates
      have decreased by 1.5% per year since 1992 among men, but have stabilized from
      1998 through 2000 among women. Cancer death rates continued to decrease from the
      three major cancer sites in men (lung and bronchus, colon and rectum, and
      prostate) and from female breast and colorectal cancers in women. In analyses by
      race and ethnicity, African-American men and women have 40% and 20% higher death
      rates from all cancers combined compared with White men and women, respectively.
      Cancer incidence and mortality rates are lower in other racial and ethnic groups
      than in Whites and African Americans for all sites combined and for the four
      major cancer sites. However, these groups generally have higher rates for
      stomach, liver, and cervical cancers than do Whites. Furthermore, minority
      populations are more likely to be diagnosed with advanced stage disease than are
      Whites. Progress in reducing the burden from cancer can be accelerated by
      applying existing cancer control knowledge into practice among all segments of
      the population.

PMID- 14974762
TI  - A new method of predicting US and state-level cancer mortality counts for the
      current calendar year.
AB  - Every January for more than 40 years, the American Cancer Society (ACS) has
      estimated the total number of cancer deaths that are expected to occur in the
      United States and individual states in the upcoming year. In a collaborative
      effort to improve the accuracy of the predictions, investigators from the
      National Cancer Institute and the ACS have developed and tested a new prediction
      method. The new method was used to create the mortality predictions for the first
      time in Cancer Statistics, 2004 and Cancer Facts & Figures 2004. The authors
      present a conceptual overview of the previous ACS method and the new state-space
      method (SSM), and they review the results of rigorous testing to determine which
      method provides more accurate predictions of the observed number of cancer deaths
      from the years 1997 to 1999. The accuracy of the methods was compared using
      squared deviations (the square of the predicted minus observed values) for each
      of the cancer sites for which predictions are published as well as for all cancer
      sites combined. At the national level, the squared deviations were not
      consistently lower for every cancer site for either method, but the average
      squared deviations (averaged across cancer sites, years, and sex) was
      substantially lower for the SSM than for the ACS method. During the period 1997
      to 1999, the ACS estimates of deaths were usually greater than the observed
      numbers for all cancer sites combined and for several major individual cancer
      sites, probably because the ACS method was less sensitive to recent changes in
      cancer mortality rates (and associated counts) that occurred for several major
      cancer sites in the early and mid 1990s. The improved accuracy of the new method
      was particularly evident for prostate cancer, for which mortality rates changed
      dramatically in the late 1980s and early 1990s. At the state level, the accuracy
      of the two methods was comparable. Based on these results, the ACS has elected to
      use the new method for the annual prediction of the number of cancer deaths at
      the national and state levels.

PMID- 14974763
TI  - American Cancer Society guidelines for the early detection of cancer, 2004.
AB  - Each January, the American Cancer Society (ACS) publishes a summary of its
      recommendations for early cancer detection, including updates, emerging issues
      that are relevant to screening for cancer, or both. In the spring of 2003, the
      ACS announced updated guidelines for breast cancer screening, and several other
      organizations released updated guidelines that we compare with recent ACS
      updates. Finally, the most recent data pertaining to participation rates in
      cancer screening are presented by age and sex from the Centers for Disease
      Control and Prevention's Behavioral Risk Factor Surveillance System, as are U.S.
      maps profiling states based on the proportion of the age-eligible population not
      recently screened for breast cancer or colorectal cancer.

PMID- 14974764
TI  - Patient pages. Finding cancer early.

PMID- 14974765
TI  - Inhaled nitric oxide therapy in the near-term or term neonate with hypoxic
      respiratory failure.
AB  - Inhaled nitric oxide (iNO) has altered the management strategy for treating near
      term and term infants with hypoxic respiratory failure (HRF). There is a strong
      relationship between HRF and persistent pulmonary hypertension of the newborn
      (PPHN). PPHN is characterized by elevated pulmonary resistance, pulmonary
      vasoconstriction, and altered vascular reactivity. The resulting high pulmonary
      pressure may lead to HRF, which is defined as a relative deficiency of oxygen in
      arterial blood and insufficient minute ventilation. iNO improves oxygenation and
      decreases the need for extracorporeal membrane oxygenation. Although iNO therapy
      is effective, its efficacy can depend on the fine points of its use and on other
      care the infant is receiving. Even in NICUs that do not have iNO available, those
      who care for term infants with HRF must be familiar with its use and know when
      and how to transfer these infants and how to help families through this difficult
      period. Because iNO therapy will probably be used more frequently in nurseries
      over the next few years, more information on the safety and efficacy of its use
      in the broader neonatal population needs to be available.

PMID- 14974766
TI  - Neonatal HIV infection.
AB  - The purpose of this article is to describe the pertinent issues related to mother
      to-child transmission of HIV infection. Significant succcss has been achieved in
      developed countries to reduce the incidence of this devastating disease in
      neonates through screening of pregnant women, maternal antiretroviral therapy to
      reduce transmission, and cesarean section for delivery. Prophylaxis continues for
      the first six weeks of the newborn's life with antiretroviral therapy and careful
      monitoring of clinical well-being. Antiretroviral therapy offers significant
      reduction in the rate of mother-to child transmission, and this is presently the
      cornerstone of therapy for the HIV-infected pregnant woman. Clinical studies of
      treatment modalities continue to offer new hope to prevent transmission of the
      virus to the fetus. Care for the HIV infected newborn is highly complex and
      constantly evolving. All neonatal nurses should be aware of these issues so that
      they can be partners in the identification of new cases and the ongoing treatment
      of babies who are infected.

PMID- 14974767
TI  - Determination of positional skin-surface pressures in premature infants.
AB  - PURPOSE: To describe the skin-surface pressure distributions and points of
      maximal pressure that are generated by healthy premature infants in the supine,
      prone, and right side-lying positions. DESIGN: A descriptive, repeated-measures
      design. SAMPLE: Four medically stable premature infants of 34 weeks
      postconceptional age. The mean weight was 2,180 gm, and the mean age was 24.5
      days. RESULTS: Similar regions of increased skin-surface pressures were
      identified for the four infants. Within areas of peak pressure, some sensor cells
      reached 28-32 millimeters of mercury, which is considered to be the critical
      compressive pressure for obstruction of nutritive flow to the underlying body
      tissues. These descriptive results may be a starting point for development of
      research studies to determine positioning strategies to optimize the skin
      integrity of premature infants while minimizing unnecessary handling.

PMID- 14974768
TI  - Recognizing and managing violence in the NICU.
AB  - PURPOSE: To determine (1) the nature and frequency of threatening or violent
      events in the NICU workplace, (2) whether nurses feel confident in their ability
      to recognize and deal with these events, (3) whether there is an association
      between violence training and confidence in the ability to recognize and manage
      violence, and (4) whether NICU nurses report and document these events. DESIGN: A
      descriptive, self administered questionnaire. SAMPLE: A nonprobability sample
      comprised of 68 RNs employed in a Level III NICU in a midwestern metropolitan
      area hospital. MAIN OUTCOME VARIABLES: Types and frequencies of threatening or
      violent events in the NICU; nurses' confidence in their ability to
      recognize/manage these events; nurses' reporting/documentation of these events.
      RESULTS: Fifty-four percent of the sample experienced threatening or violent
      workplace events; 83.8 percent of the sample felt confident in their ability to
      recognize violent situations; 69.1 percent felt confident in their ability to
      manage violent situations. Various means were reported for documenting and
      reporting such events, but 27 percent neither reported nor documented violent
      events.

PMID- 14974769
TI  - It's always something.

PMID- 14974770
TI  - The high-risk infant is going home: what now?

PMID- 14974771
TI  - Toy or tool of the trade? Part II.

PMID- 14974772
TI  - Validity and reliability: part I.
AB  - Internal and external validity of a study determine the generalizability of its
      findings. Measurement reliability and validity, which also have an impact on the
      overall validity of the study, will be discussed in the next column. Although the
      concepts have been pulled apart for this discussion, all of these factors
      influence the overall confidence with which researchers can say that they have
      measured what was intended and that the findings can be applied to a larger
      population of individuals.

PMID- 14974773
TI  - Findings from the National Institute of Nursing Research related to neonatal
      care.

PMID- 14974774
TI  - Work-related mortality among British seafarers employed in flags of convenience
      shipping, 1976-95.
AB  - OBJECTIVE: To establish and analyse the causes and circumstances of all deaths
      among British seafarers who were working in flags of convenience merchant
      shipping between 1976 and 1995, to compare mortality with British seafarers
      employed in British merchant shipping, and to discuss implications for health and
      safety. METHODS: A retrospective longitudinal study of occupational mortality,
      based on official mortality files. RESULTS: Out of a total of 200 deaths in flags
      of convenience shipping, illnesses caused 68 deaths, accidents 91, homicide 3,
      suicide 7, drug and alcohol intoxication 4, and disappearances at sea and other
      unknown causes 27. Deaths from non-natural causes and, in particular, maritime
      disasters accounted for a significantly higher proportion of all deaths in flags
      of convenience than in British shipping. The maritime disasters largely involved
      small cargo ships foundering or disappearing in bad weather. CONCLUSIONS:
      Although mortality rates could not be calculated, because of the unavailability
      of population information, British seafarers who work for flags of convenience
      registries appear to be at increased risk of mortality through maritime
      disasters, as well as through occupational accidents and suicide. Many of the
      occupational accidents, such as asphyxiation in cargo holds, were caused by
      hazardous working practices, and the disappearances of small cargo ships raises
      questions about their seaworthiness. Future efforts should focus on investigating
      the mortality and health of seafarers working in flags of convenience ships, and
      on improving mortality and population information systems for these registries.

PMID- 14974775
TI  - Myocardial infarction (MI) at the work-site among Polish seafarers. The risk and
      the impact of occupational factors.
AB  - OBJECTIVES: To study the incidence of myocardial infarction (MI) on board ship,
      the impact of conditions of work on the mortality and survival rate, to analyze
      the recommendations and possible preventive interventions to reduce the loss of
      life at the work-site among Polish seafarers and deep-sea fishermen. METHODS: To
      use various sources of information for the retrospective study of the MI
      incidence among 11,325 Polish seamen and deep-sea fishermen. To analyse the
      impact of the marine environment and work-related factors on the course,
      treatment and prognosis of MI. The results were compared with the incidence and
      mortality rate of MI among general male workers population in Poland. RESULTS: In
      this retrospective study, 106 cases of the MI at sea were included. Their
      diagnosis was based on the medical documentation and legal investigation of
      cases. The most significant findings seem to indicate that the incidence of MI at
      the work-site among Polish seafarers was not higher than among general population
      of Polish males in the same decade, probably due to the "healthy worker" effect.
      However, the pre-hospital and one-month mortality due to MI were higher in the
      group of seafarers as compared to the group of general male population. The
      analysis of conditions of seafarers' work and life and the possibility of
      treatment at sea in a case of the MI on board strongly suggest that the work
      related factors had significant impact on the loss of life among them. The
      preventive measures, very complex and difficult from the organizational and
      economic point of view, are still far from being recommended and implemented in
      the shipping industry. CONCLUSIONS: The study has confirmed that seafarers are at
      high risk of death in case of a MI on board. The impact of their work environment
      and work-related factors reduce significantly the chance of survival at sea in
      such cases. The preventive measures are difficult to implement.

PMID- 14974776
TI  - Selected risk factors of ischemic heart disease in Polish seafarers. Preliminary
      report.
AB  - Cardiovascular diseases are a serious health problem for seafarers. Work-related
      exposures, their diet and limited physical exercise during work at sea are
      contributing factors for the development of ischemic heart disease (IHD) in this
      group of workers. The objective of the present study was determination of
      incidence of selected risk factors of IHD, such as overweight and obesity,
      tobacco smoking, arterial hypertension, type 2 diabetes mellitus, dyslipidaemia,
      and elevated serum concentration of uric acid. A survey was conducted in 1998
      2001 among 715 Polish seafarers examined at the Institute of Maritime and
      Tropical Medicine in Gdynia. One or more of the above risk factors were detected
      in 593 examined persons (82.9%). A single risk factor was present in 30.5% of the
      study population, two factors in 50.3% three factors in 13.2%, while four or more
      risk factors were present in 6% of examined seafarers. The authors suggest that,
      during the periodic medical examinations, physicians should advice seafarers
      about prevention of cardiovascular disease, and those of them in whom three or
      more risk factors of IHD are detected, should be referred to cardiological
      consultation comprising the assessment of coronary performance (exercise test).

PMID- 14974777
TI  - Prevention of post traumatic stress disorder amongst maritime pilots.

PMID- 14974778
TI  - The social isolation of seafarers: causes, effects, and remedies.
AB  - The human element is increasingly acknowledged as an important factor
      contributing to accidents at sea. What is infrequently considered however, is the
      extent to which social isolation, and its effects on seafarers, contributes to
      both marine incidents and to the problems of seafarer retention currently
      experienced throughout the industry as a whole. This paper draws on the findings
      of several related studies undertaken at the Seafarers International Research
      Centre (1999-2002) along with a number of published studies on seafarer health.
      In doing so it considers both the causes and potential effects of social
      isolation on seafarers. These areas have not traditionally been subject to
      systematic scrutiny and analysis. As such they are substantially under-researched
      and are often under-emphasised by policy makers and practitioners in the maritime
      sector. Using participant observation and detailed qualitative studies the paper
      explores these issues in an effort to bring them on to the accident prevention
      agenda and to highlight the need for further detailed research in this area. In
      drawing to a conclusion the paper highlights a number of steps that could be
      taken by shipping companies to militate against social isolation and to encourage
      better mental health amongst modern day seafarers.

PMID- 14974779
TI  - Psychological evaluation of seafarers.
AB  - The CIA Factor Assessment is a psychological testing and related research
      activities carried out under auspices of Wartsila Land and Sea Academy at WLSA
      Regional Training Centre in the Philippines in June 2003. The purpose was to
      evaluate seafarers against their mental and physical health and obtain their
      charachteristic as individuals and as a group. The CIA (Consciousness, Intuition.
      Anticipation, professional psychometric testing) is a set of tests covering three
      essential values to determine one's suitability and fitness for work at sea
      developed in order to recognize and improve potentials of professional seafarers.
      The results of the evaluation were good. The examined persons had good or very
      good scores, only few of them were below average, requiring professional
      individual psychological attention/assistance, extended specialized training, or
      intensive pertinent testing.

PMID- 14974780
TI  - Regulations and control of in-transit fumigated containers as well as of
      fumigated cargo ships.
AB  - INTRODUCTION: According to IMO's international regulations, e.g. "Recommendations
      on the safe use of pesticides in ships", fumigated containers and ship cargoes
      must be labeled giving specifications about dates of fumigation and the
      fumigation gas used. Furthermore, appropriate certificates are necessary and
      these records have to be forwarded to the Port Health Authorities without their
      explicitly asking for them. BACKGROUND AND OBJECTIVES: According to IMO
      (DSC/Circ.8.24.7.2001) a recent inspection of containers unloaded in ports showed
      that some were under fumigation, but not declared as such and in a few cases
      these ventilated containers arrive with "Degas Certificates" stating that
      fumigant has been removed, but still have a high fumigant concentration inside
      when opened. There are similar reports from The Netherlands, where 21% of the
      fumigated containers had missing or false declarations and contained measurable
      amounts of toxic gas. In England 6% were mentioned to be allegedly false. Reports
      exist of a number of other incidents with containers under fumigation arriving in
      English ports with no accompanying documents on the ship or at the port of
      discharge as to the type of cargo. In one case several people were hospitalized
      after exposure to phosphine gas because the fumigant tablets were not yet totally
      decomposed before the ship arrived at its destination port. In Bavaria, Germany,
      a bad accident recently occurred through a non declared fumigated container (see
      press release). Our sample: a large container ship in the Port of Hamburg where
      27 of the cargo's containers were found fumigated with 27 non/incomplete/false
      declarations. These examples show that missing/false labelling is frequent.
      CONCLUSIONS AND RECOMMENDATIONS: Clearance of in-transit fumigated containers in
      ports is complicated and time-consuming for the captain and shipping company. The
      above mentioned accident and also the results of our spot check prove, as do the
      experiences in The Netherlands and England, that false declarations of fumigated
      containers seem commonplace. This coincides with a considerable danger for ship
      crews, port workers and end users. More stringent controls, including gas
      analysis, are necessary as well as a systematic study. As a first step in that
      direction, we included the question "Are fumigated containers on board?", in the
      form of the Maritime Declaration of Health we demand. A computer controlled
      information and communication system network between ports and its link with the
      Waterways and Shipping Directorate would enable comprehensive plausibility
      monitoring and thus help achieve a better surveillance.

PMID- 14974781
TI  - Life rafts--ventillation is vital.

PMID- 14974782
TI  - Malaria relapse and recrudescence among travellers to the tropics.
AB  - This study describes 14 cases of relapse and recrudescence of malaria, treated
      between 1991 and 2003. In that period, 146 patients were hospitalized in the
      Clinic of the Institute in Gdynia: 20 women and 126 men. In 103 cases the disease
      was caused by Plasmodium falciparum, in 31 cases by Plasmodium vivax, in 5 cases
      by Plasmodium malariae, and in 2 cases by Plasmodium ovale. Five patients were
      found to have mixed infections, with either P. falciparum and P. vivax or P.
      falciparum and P. ovale. Relapses in patients previously treated in the country
      or abroad accounted for 9.6% of all the treated cases of malaria. Recrudescences
      and relapses were diagnosed of both the tropical malaria (6 cases), and the
      tertian malaria caused by P. vivax (4 cases). Moreover, in 4 patients diagnosis
      was made of secondary malaria due to P. vivax infection, while the primary attack
      was caused by invasion of P. falciparum. Also discussed was the issue of drug
      resistance of plasmodia and the resulting problems with the treatment.

PMID- 14974783
TI  - Sexually transmitted diseases among Polish soldiers serving in the U.N. peace
      missions in Lebanon and Cambodia.
AB  - The results are presented of a survey conducted on the incidence of sexually
      transmitted diseases (STD) among Polish military personnel of the United Nations
      Forces in Lebanon (UNIFIL) in 1993-2000, and Cambodia (UNTAC) in 1992-1993. The
      analysis was based on the medical documentation of the patients treated in the
      UNIFIL Hospital in years 1993-2000. The most frequently recorded cases of
      sexually transmitted diseases in Cambodia were those of gonorrhoea. The results
      showed that sexually transmitted diseases did not present a serious health
      problem among soldiers in Lebanon, but were a problem in Cambodia. Specific
      living conditions and social norms characteristic for these countries were taken
      into consideration in presenting the results of the survey.

PMID- 14974784
TI  - The maximum tissue half-time for nitrogen elimination from divers' body.
AB  - Both the longest tissue half-time (T1/2max) and the maximum allowable pressure
      gradient (deltaP) define the safe rate of decompression (DR) after saturation
      expositions. The mathematical relation between them (DR = -k x deltaP, where: k =
      ln(2)/(T1/2max)) suggests that experimentally established decompression rate can
      be hypothetically described by the infinite number of T1/2max and deltaP
      combinations. The observed number of decompression sickness after saturation
      decompressions forced to change those parameters subsequently and finally led to
      values far outside physiological range. Therefore the aim of this study was to
      compare values of the longest tissue half-time of nitrogen desaturation from
      diver's body published since 1908 in order to present the evolution of opinions
      concerning desaturation process. Non-physiological values of T1/2max (from 75 to
      1280 minutes) have been published during historical evolution of decompression
      tables and systems. The currently accepted values of T1/2max (in the range of 320
      480 minutes) for saturation and non-saturation air and nitrox divings and
      hypobaric decompressions, still need to be precised. The discrepancy between
      T1/2max values obtained using isobaric decompression method and decompressions
      after diving indicates different physiological phenomena during nitrogen
      elimination in both methods.

PMID- 14974785
TI  - Oxidative stress during oxygen tolerance test.
AB  - Reactive oxygen species, including oxygen free radicals are normally generated in
      human cells during aerobic metabolism. Their production may increase during
      breathing of hyperoxic mixtures. The 'oxidative stress' has been postulated to be
      an important contributor to CNS oxygen toxicity. One of the highest partial
      pressure of oxygen used in healthy humans is 280 kPa(a) during 30 min of 'oxygen
      tolerance tests' (OTT). This test is conducted in order to detect some
      individuals with an increased sensitivity to high partial pressures of oxygen
      leading them to develop CNS oxygen toxicity earlier than others. The purpose of
      this study was to investigate whether the OTT (30 min of breathing pure oxygen at
      280 kPa(a)) would significantly induce oxidative stress in healthy population.
      The first group consisted of 52 subjects, in whom total antioxidant status (TAS)
      was measured. The second group consisted of 44 subjects, in whom protein
      carbonyls (PC), total thiol (t-SH) and heat shock proteins (HSP70) were measured.
      All measurements were done just before and immediately after the OTT. There was
      no statistically significant change of TAS. We observed a small, however
      statistically significant increase of PC and decrease of t-SH. A significant
      decrease of HSP70 was detected, however false positives of initial measurements
      are suspected. In summary, in young healthy subjects 30 min of breathing oxygen
      under pressure of 280 kPa(a) induces oxidative stress which can be detected by
      increase of protein carbonyls and by decrease of total thiol. In our study this
      stress was not reflected in measurement of total oxidative status and heat shock
      proteins.

PMID- 14974786
TI  - Change of occurance of type 1 and type 2 decompression sickness of divers treated
      at the Croatian Naval Medical Institute in the period from 1967 to 2000.
AB  - A significant change of occurrence (p=0.0343) of type 1 and type 2 decompression
      sickness (DCS) of divers in Croatia was observed in the period from 1991 to 2002
      (type 1: n=26, 37.68% and type 2: n=43, 62.32%) compared with the period from
      1967 to 1990 (type 1: n=93, 52.84% and type 2: n=83, 47.16%). The change was
      attributed to the extensive usage of diving computers and artificial gas mixtures
      which enable extended bottom times and deeper dives, thus putting divers at an
      increased decompression risk. The importance of the results of this report is in
      the fact that permanent neurological deficit occurs only after type 2 DCS.
      Injured divers with permanent loss after type 2 DCS are not fit for diving and
      require a long term medical care, thus becoming a significant public health
      problem.

PMID- 14974787
TI  - Standards on medical fitness examinations for Navy divers.
AB  - The German Navy employs approximately 480 divers in their primary and secondary
      role. Before entering diving training, every diver has to pass an intensive
      physical examination programme at the German Naval Medical Institute (NMI) in
      Kiel-Kronshagen. Annual follow-ups ensure the currency of the medical findings.
      Criteria of medical fitness for diving reflect industrial medical standards for
      hyperbaric workers as well as the general medical guidelines for NATO divers. A
      diving examination consists of the individual medical history, a physical
      examination including the neurological status and the assessment of the
      cardiovascular fitness by ECG and bicycle ergometry. The respiratory system is
      screened by regular chest x-rays and spirometry or body plethysmography. Blood
      and urine samples are taken to look for abnormal haematological and metabolic
      conditions as well as disorders of the genito-urinary system. In order to
      determine visual fitness, diver's visual acuity, colour vision and stereopsis as
      well as eye fundi are examined by an eye specialist. Also the ENT examination
      involves a speciality consultant and consists of audiometry, inspection of the
      external ear and tympanic membrane and functional tests. To ensure a high
      standard of dental fitness, screening by a dental officer is part of the annual
      check-up. Every routine diving medical examination at the NMI includes a pressure
      test in the hyperbaric chamber. Divers who use nitrox or oxygen-rebreather
      devices have to pass successfully an oxygen tolerance test under hyperbaric
      conditions. The annual routine diving medical examination contributes to minimize
      the risk of accidents in military diving operations.

PMID- 14974788
TI  - The network of WHO Collaborating Centres in Occupational Health and the role of
      maritime centres.
AB  - The WHO Network of Collaborating Centres in Occupational Health comprises 70
      Collaborating Centres. Four of these Centres are specialised in Maritime
      Occupational Health and they are situated in Poland, Germany, Denmark and the
      Ukraine. All Collaborating Centres follow the mandate of the Occupational Health
      Programme in WHO, which is the Global Strategy on Occupational Health for All.
      Collaborating Centres in Maritime Occupational Health cover a specific group of
      workers who are exposed to different work environments than workers on land. They
      are often not at all or only insufficiently covered by any health services. The
      Collaborating Centres in Maritime Occupational Health provide an excellent
      example of international collaboration.

PMID- 14974789
TI  - Safety and health in the fishing industry.
AB  - Safety and health problems of fishermen are reviewed in this article, including
      work related accidents and illness and their costs, and national and
      international preventive interventions. The article also discusses current ILO
      action to address these issues.

PMID- 14974790
TI  - The Lithuanian Maritime Medical Center in Klaipeda.

PMID- 14974791
TI  - The principles of writing the medical guide for ships.
AB  - The medical training and skills of seafarers are rather limited. In Finland, the
      master is responsible for medical care of his crew members, having only a 5-day
      training in medical matters which is refreshed every year. As medical incidents
      are rather rare events on board ship, he has not many opportunities to increase
      his knowledge in this field. Highly educated and experienced medical doctors have
      written medical guides for ships, describing diseases and advising on their
      treatment. This advice is based on diagnoses made on board ship by masters. They
      are often incorrect, therefore the advice on treatment may also be not correct.
      Authors of medical guides for ships should take into consideration the limited
      skills and medical knowledge of persons responsible for providing health services
      for crews at sea. This service is usually limited to giving first aid in
      accidents and sudden diseases, and care of the injured or sick seafarer until he
      can be transported to a medical facility on shore. Long lists of possible
      diagnoses in the text of such a guide only cause confusion in situations on board
      ship. In the new edition of the guide published in Finland in 2002, the advice on
      treatment is based on symptoms rather than on diagnoses.

PMID- 14974792
TI  - Activities in maritime medicine in countries of Central and Eastern Europe:
      symposia on maritime medicine, 1963-1989.
AB  - The history of a line of international symposia on maritime medicine conducted in
      1963-1989 in countries of Central and Eastern Europe is presented.

PMID- 14974793
TI  - Keeping criticism at bay: suggestions for forensic psychiatry experts.

PMID- 14974794
TI  - Should forensic psychiatrists testify about evil?

PMID- 14974795
TI  - Response to Simon: Legal relevance demands that evil be defined and standardized.

PMID- 14974796
TI  - "The whole truth" versus "the admissible truth": an ethics dilemma for expert
      witnesses.
AB  - The expert witness testifies under oath to tell "the whole truth," yet certain
      aspects of the legal system itself make this ideal difficult or impossible. The
      authors present both a philosophical and a practical discussion of the challenges
      for the expert in attaining this goal. After review of oaths in general and truth
      telling in particular, real-life examples are provided to examine the
      vicissitudes of the whole truth in court. Recommendations are provided for
      experts, to preserve the truth in the adversary system.

PMID- 14974797
TI  - Truth in forensic psychiatry: a cultural response to Gutheil and colleagues.

PMID- 14974798
TI  - Stalking and serious violence.
AB  - Studies of violence in stalking have treated interpersonal violence as a
      homogeneous phenomenon. This study was conducted to ascertain whether the
      associations of serious violence in stalking are the same as those of general
      violence in stalking. Of 85 stalkers referred to a forensic service, those who
      had committed acts of serious violence (homicide and serious assaults) were
      compared with those who had not on preselected clinical, demographic, and
      criminological variables. Associations of serious violence were found to differ
      from those reported for general violence. In particular, serious violence was
      significantly associated with an absence of criminal convictions and the presence
      of employment. There was no association with substance abuse, previous
      convictions for violence, or personality disorder. Different degrees of violence
      have different associations. This has implications for the development of
      violence prediction instruments and for violence prevention in stalking.

PMID- 14974799
TI  - Commentary: Update on assessing risk for violence among stalkers.

PMID- 14974800
TI  - Concealment of psychopathology in forensic evaluations: a pilot study of
      intentional and uninsightful dissimulators.
AB  - Dissimulation is the concealment of genuine psychiatric symptoms in an attempt to
      present a picture of psychiatric health. In this pilot study, the authors set out
      to demonstrate that defendants may conceal psychiatric illness even in forensic
      settings, contrary to their apparent self-interest. They reviewed their records
      for forensic assessments of dissimulators and malingerers and classified
      dissimulators as "intentional" or "uninsightful" depending on whether their
      concealment of symptoms appeared to be a volitional act or driven by a lack of
      insight. Although there were obvious diagnostic differences, the only other
      significant difference between malingerers and dissimulators was that malingerers
      were more likely to be facing charges related to financial crimes. Uninsightful
      dissimulators were significantly older than were intentional dissimulators.
      Uninsightful dissimulators were also more likely to be psychotic, particularly
      delusional and schizophrenic, than were intentional dissimulators. While forensic
      psychiatrists are vigilant in attempts to detect malingering, these data suggest
      that they should be equally vigilant regarding the possibility of dissimulation.
      Although further study is indicated, it appears that dissimulators are a
      heterogeneous group.

PMID- 14974801
TI  - Confessions and expert testimony.
AB  - In this clinical paper, the author discusses criminal confessions from the point
      of view of the expert witness who may be asked to comment on the reliability of
      the statement and waiver of rights. From the time a suspect is in police custody,
      constitutional protections against self-incrimination and for due process are in
      place. The Supreme Court set the standard for these situations in the 1966
      Miranda v. Arizona decision. Although it has long been criticized by law
      enforcement, the decision was upheld in the 2000 decision in Dickerson v. U.S.
      For a waiver of rights to be valid, it must be a knowing, intelligent, and
      voluntary decision. Voluntariness is an equation of objective and subjective
      variables. Treatment by police, physical conditions of interrogation, the
      suspect's experience and mental state can alter the reliability of a confession.
      Accordingly, the author has devised a mnemonic for the recognition of conditions
      that may give rise to expert testimony. The conditions are: Mental illness,
      Intoxication, Retardation, Acquiescence, Narcotic withdrawal, Deception, and
      Abuse. These are discussed, supported by examples from the author's practice.

PMID- 14974802
TI  - Filicidal mothers and the impact of psychosis on maternal filicide.
AB  - The objective of this study was to examine a sample (n = 55) of filicidal mothers
      to compare those with and without psychotic symptoms at the time of the filicide.
      Clinical data were gathered through retrospective chart review of filicidal women
      referred for criminal responsibility/competence to stand trial evaluations from
      1974 to 1996 at Michigan's Center for Forensic Psychiatry. Most (52.7%) women had
      psychotic symptoms at the time of filicide. Women with psychosis were more likely
      than those without to have a history of substance abuse; to have past and ongoing
      psychiatric treatment; and to be older, unemployed, more educated, and divorced
      or separated. They were less likely to be first time mothers or to have had prior
      contact with Children's Protective Services. The psychotic mothers more often
      confessed, attempted suicide at the time of the filicide, used weapons, killed
      multiple children, and expressed homicidal thoughts and/or concerns about their
      children to psychiatrists and family before the filicide. Psychotic women were as
      likely as nonpsychotic women to have used alcohol or illegal drugs at the time of
      the filicide.

PMID- 14974803
TI  - Expert testimony in sexually violent predator commitments: conceptualizing legal
      standards of "mental disorder" and "likely to reoffend".
AB  - The most recent type of civil commitment for dangerous sex offenders is found
      under the sexually violent predator laws. Forensic psychiatrists or psychologists
      must render an opinion as to whether the sex offender has a diagnosed mental
      disorder and, as such, represents a risk to public safety if released from
      custody into the community. Thus, expert testimony provided by these
      professionals has taken a central role in the commitment determinations. There is
      considerable debate as to what disorders predispose individuals to sexual
      recidivism and what the term "likely" signifies. In this article, the authors
      explore the debate in terms of whether Antisocial Personality Disorder is a
      qualifying diagnosed mental disorder for classification as a sexually violent
      predator and how a likely threshold of risk of sexual recidivism can be
      conceptualized.

PMID- 14974804
TI  - Psychosocial and biological treatment considerations for the paraphilic and
      nonparaphilic sex offender.
AB  - There is a growing consensus among clinicians that sex offenders represent a
      heterogeneous group of individuals. Assessment and treatment of sex offenders is
      complicated by phenomenological and etiological differences and the presence of
      psychopathology, including paraphilias. The authors discusses the most commonly
      employed psychosocial therapies for sex offenders in general. Pharmacologically
      based treatments for paraphilic sex offenders are also reviewed.

PMID- 14974805
TI  - Sex offender registration and community notification challenges: the Supreme
      Court continues its trend.
AB  - All states and the District of Columbia have passed sex offender registration and
      community notification laws. While the specific provisions of these statutes
      vary, all have public safety as a primary goal. The authors discuss two recent
      cases heard by the United States Supreme Court that challenged the
      constitutionality of Alaska's and Connecticut's statutes. The laws were
      challenged as violations of the United States Constitution's prohibition on ex
      post facto laws and its Fourteenth Amendment guarantee of procedural due process.
      In both cases, the statutes were upheld. As it has found in challenges to
      sexually violent predator statutes, the Court emphasized that the registration
      and community notification schemes are civil and not criminal in nature. The
      article concludes with a discussion of possible implications for clinicians
      involved in evaluating or treating sex offenders.

PMID- 14974806
TI  - Castration of sex offenders: prisoners' rights versus public safety.
AB  - Sexual victimization of children and adults is a significant treatment and public
      policy problem in the United States. To address increasing concerns regarding sex
      offender recidivism, nine states have passed legislation since 1996 authorizing
      the use of either chemical or physical castration. In most statutes, a repeat
      offender's eligibility for probation or parole is linked to acceptance of
      mandated hormonal therapy. Future legal challenges to this wave of legislation
      will probably include arguments that such laws violate constitutional rights
      guaranteed to the offender by the First, Eighth, and Fourteenth Amendments. When
      the promise of freedom is predicated on mandated treatment, the clinician must
      carefully assess the validity of informed consent.

PMID- 14974807
TI  - Sex offender treatment and legislation.
AB  - The current issue of the Journal contains three articles related to sex
      offenders. The first, by Scott and Holmberg, discusses legislation that mandates
      either "chemical or surgical castration." The second, by Saleh and Guidry,
      reviews diagnostic and treatment considerations. The third, by Scott and Gerbasi,
      discusses sex offender registration and community notification. Much of the
      relevant sex offender legislation, including that pertaining to testosterone
      lowering treatments, has been enacted in response to intense public passion. When
      it comes to the issue of sex offenders, there is a pressing need to develop a
      coherent body of evidence-based forensic concepts and knowledge that can
      rationally inform both clinical practice and future public policy. That may
      require a closer collaboration between both the criminal justice and legislative
      sectors, and the scientific-medical communities. The three papers published in
      this issue provide useful information that may assist toward such a goal.

PMID- 14974808
TI  - Prosecutions of patients because of the actions of their psychiatrists.

PMID- 14974809
TI  - Tarasoff warnings result in criminal charges.

PMID- 14974810
TI  - Slater Method.

PMID- 14974811
TI  - Effect of Porphyromonas gingivalis lipopolysaccharide, tumor necrosis factor
      alpha, and interleukin-1beta on calprotectin release in human monocytes.
AB  - BACKGROUND: Calprotectin is a major cytosolic protein of monocytes, granulocytes,
      and epithelial cells. It is known that calprotectin is released in inflammatory
      tissues and detected in gingival crevicular fluid (GCF) of periodontitis patients
      at high levels. The origin of calprotectin in GCF and its regulation in
      periodontal disease are unknown. In this study, we investigated the distribution
      of calprotectin in gingival tissue with inflammation and the induction of
      calprotectin release from human monocytes by lipopolysaccharide of Porphyromonas
      gingivalis (P-LPS), tumor necrosis factor-alpha (TNF-alpha), or interleukin-1beta
      (IL-1beta). METHODS: Gingival tissues were obtained from a healthy donor and a
      periodontitis patient and calprotectin in gingival tissues was examined by
      immunohistochemical staining. Monocytes were isolated from the peripheral blood
      of healthy donors and cultured with P-LPS, TNF-alpha or IL-1beta for 30 minutes
      to 4 hours. The content of calprotectin in the cell and medium fractions was
      determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Calprotectin
      was markedly detected at the epithelial and adjacent connective tissue with many
      inflammatory cells in the gingival tissue from the periodontitis patient. P-LPS
      increased calprotectin release from monocytes to the maximum level after 30
      minutes of treatment and its level was elevated to about 2- to 3-fold of the
      control level in a dose-dependent manner (1 to 1,000 ng/ml). When the effect of
      TNF-alpha and IL-1beta on calprotectin release was investigated, calprotectin
      release significantly increased to about 2.2- and 1.5-fold that of the control
      level, respectively. CONCLUSION: These results demonstrate that calprotectin
      release from monocytes is induced by P-LPS, TNF-alpha, and IL-1beta, which in
      turn, cause and aggravate periodontal disease.

PMID- 14974812
TI  - Enamel matrix proteins and bovine porous bone mineral in the treatment of
      intrabony defects: a comparative controlled clinical trial.
AB  - BACKGROUND: Various clinical studies have demonstrated that applying commercially
      available enamel matrix proteins (EMP) on the instrumented root surface during
      access flap surgery promotes clinically significant gains of clinical attachment
      and bone in intrabony defects. The aim of the present controlled clinical trial
      was to evaluate the adjunctive effect of filling the intrabony lesion with bovine
      porous bone mineral (BPBM) to a simplified papilla preservation (SPP) flap and
      EMP surgical procedure. METHODS: Sixty deep interproximal intrabony lesions in 60
      patients with chronic periodontitis were treated with the SPP flap and EMP. In
      the 30 test defects, the intrabony component was filled with BPBM particles
      previously reconstituted with the EMP gel. A stringent infection control program
      was adopted for 1 year. The clinical and radiographical reevaluation was made 1
      year after surgery. RESULTS: Both techniques resulted in clinically and
      statistically significant improvements between baseline and 1 year, in terms of
      clinical attachment level (CAL) gain, probing depth (PD) reduction, and
      radiographic bone fill; however, the BPBM test treatment showed statistically
      significantly greater CAL (5.8 +/- 1.1 versus 4.9 +/- 1.0) and radiographic bone
      (DEPTH) level gains (5.3 +/- 1.1 versus 4.3 +/- 1.5), and less increase in
      gingival recession (0.4 +/- 0.6 versus 0.9 +/- 0.5) than the control surgical
      procedure. CONCLUSION: The present study data supported the hypothesis that the
      adjunctive use of BPBM in grafting intrabony defects has the ability to improve
      clinical and radiographical outcomes achievable with EMP alone.

PMID- 14974813
TI  - Reproducibility of probing depth measurement using a constant-force electronic
      probe: analysis of inter- and intraexaminer variability.
AB  - BACKGROUND: Probing depth (PD) is a commonly used method to determine periodontal
      disease severity in both treating and evaluating disease progression. Agreement
      among examiners collecting data in scientific investigations is necessary to
      establish reliable criteria for determining levels of periodontal attachment
      loss. The objective of our study was to evaluate inter- and intraexaminer
      variability of PD measurements among study examiners using a constant force
      periodontal probe, and to compare the variability of tooth-mean and quadrant
      mean. METHODS: Three examiners, who had been previously trained and calibrated,
      performed measurements on 20 volunteers. Intra- and interexaminer variability of
      sites was determined by means of standard error of measurement (SE). Data
      analysis included determination of error for both quadrant mean and tooth mean.
      RESULTS: PD measurements for the quadrant-mean were used to calculate the
      intraexaminer variability, resulting in a mean (SD) value for an SE of 0.40 mm
      (+/- 0.02). Interexaminer variability for quadrant mean was 0.16 mm (+/- 0.02).
      For tooth-mean SE, the intraexaminer variability values were equal to 0.38 mm (+/
      0.07), and interexaminer variability equal to 0.24 mm (+/- 0.05). CONCLUSIONS:
      All three examiners participating in our study were able to obtain reliable
      measurements for PD, using the constant force electronic probe. Reproducibility
      did not vary appreciably when using the whole quadrant mean compared to the tooth
      mean. These trained examiners were able to provide reproducible measures under
      0.5 mm.

PMID- 14974814
TI  - Association between alveolar bone loss and elevated serum C-reactive protein in
      Japanese men.
AB  - BACKGROUND: Moderate elevation of C-reactive protein (CRP) is thought to predict
      type 2 diabetes and cardiovascular disease (CVD), both of which are associated
      with periodontitis. Recent studies indicate that periodontal disease is
      associated with moderate elevation of CRP; however, the relationship between
      alveolar bone loss (ABL) and CRP elevation is unclear. METHODS: A total of 179
      Japanese men aged 50 to 54 years old, with at least 10 teeth, were examined as
      part of a comprehensive health examination before retirement from the Japan Self
      Defense Force. ABL was measured at proximal sites of posterior teeth on a
      panoramic x-ray film. The relationship between the mean ratio of ABL to root
      length and serum CRP level and other variables was analyzed. RESULTS: ABL was
      significantly correlated with serum CRP level (P = 0.008), alkaline phosphatase
      (P = 0.008), high-density lipoprotein (HDL) cholesterol (P = 0.04, inversely),
      white blood cell count (P < 0.001), erythrocyte sedimentation rate (P = 0.002),
      age (P = 0.03), and smoking history (P < 0.001). In a multiple logistic
      regression model adjusted for age, smoking history, systolic blood pressure, body
      mass index, triglyceride, and HDL cholesterol, subjects in the highest tertile of
      ABL had an increased risk for CRP elevation > or = 1.3 mg/l (odds ratio [OR] =
      8.20; 95% confidence interval [CI], 1.6 to 40.7; P = 0.01) when compared to the
      lowest tertile of ABL. CONCLUSION: ABL around posterior teeth was associated with
      elevated CRP in Japanese men, suggesting an association between periodontal
      disease and increased risk of type 2 diabetes and CVD.

PMID- 14974815
TI  - Gene expression of extracellular matrix proteoglycans in human cyclosporin
      induced gingival overgrowth.
AB  - BACKGROUND: Gingival overgrowth is one of the side effects associated with the
      systemic use of cyclosporin A (CsA). In vitro studies on the extracellular matrix
      of gingival tissues have demonstrated an altered composition, particularly an
      accumulation of proteoglycans and collagen. We investigated the gene expression
      of extracellular matrix proteoglycans in CsA-induced gingival tissue alterations.
      METHODS: mRNA expression of the proteoglycans perlecan, decorin, biglycan, and
      versican was analyzed by reverse transcription polymerase chain reaction (RT-PCR)
      in gingival samples obtained from 12 individuals, six with CsA-induced gingival
      overgrowth (CsA group) and six with a normal gingiva (control group). The RT-PCR
      products were subjected to 1% agarose gel electrophoresis containing ethidium
      bromide and analyzed qualitatively and semiquantitatively by densitometry.
      Density values were normalized by determining the expression of the housekeeping
      gene beta-actin in the same sample. Groups were compared by the Student's t test.
      RESULTS: Perlecan expression showed a marked increase (54%) in the CsA group
      compared to the control group (P < 0.01), while no significant differences were
      observed for the other proteoglycans. CONCLUSION: CsA-induced gingival overgrowth
      seems to be associated with increased expression of perlecan, a typical basement
      membrane proteoglycan, but not decorin, biglycan, or versican.

PMID- 14974816
TI  - Cyclooxygenase-2 inhibitors decrease interleukin-1beta-stimulated prostaglandin
      E2 and IL-6 production by human gingival fibroblasts.
AB  - BACKGROUND: Previous work showed that normal and aggressive periodontitis (AgP)
      gingival fibroblasts produce the bone-resorbing cytokine IL-6. PGE2 is important
      in regulating IL-6 production. Non-steroidal anti-inflammatory drugs inhibit PG
      synthesis via COX-1 and/or COX-2 isoenzymes and may inhibit periodontal
      destruction. COX-2 is induced after cellular activation (i.e., by inflammatory
      cytokines such as IL-1beta). Little is known about IL-1beta-stimulated AgP
      fibroblast IL-6 and PGE2 production and their regulation by COX inhibitors. The
      objective of this study was to determine the effects of COX-2 inhibitors on
      amounts of PGE2 and IL-6 made by IL-1beta-stimulated gingival fibroblasts.
      METHODS: Gingival fibroblasts (2.5 x 10(4)) from healthy or severe periodontitis
      patients were cultured in serum-free medium, with or without IL-1beta (10(-11)M)
      for 24 hours, with or without the COX-1/2 inhibitor indomethacin or the selective
      COX-2 inhibitors NS-398, celecoxib, or rofecoxib. PGE2 and IL-6 in culture
      supernatants were determined by specific enzyme-linked immunosorbent assay
      (ELISA)s. RESULTS: All of the COX inhibitors caused dose-dependent decreases in
      IL-1beta-stimulated PGE2, to a maximum of > 90% in all cell lines (P < or =
      0.0001). The selective COX-2 inhibitors, but not indomethacin, caused partial
      (generally up to approximately 60%), dose-dependent decreases in IL-1beta
      stimulated IL-6 in all cell lines (P < or = 0.003). When exogenous PGE2 was added
      concurrently with COX-2 inhibitors before addition of IL-1beta, IL-6 production
      returned to levels at or approaching that produced by cells exposed only to IL
      1beta (P < or = 0.04). CONCLUSION: The results suggest that COX-2 inhibition may
      be useful in helping to control fibroblast production of IL-6 in patients with
      severe periodontitis.

PMID- 14974817
TI  - Associations between systemic status, periodontal status, serum cytokine levels,
      and delivery outcomes in pregnant women with a diagnosis of threatened premature
      labor.
AB  - BACKGROUND: Threatened premature labor (TPL) often results in preterm birth (PB).
      The aim of the present study was to evaluate the associations of periodontal and
      general health conditions with TPL and PB in relation to serum cytokine levels
      and the composition of subgingival plaque. METHODS: Eighty-eight women were
      enrolled in the study. Systemic conditions were assessed, and subgingival plaque
      samples obtained for bacterial analysis. Periodontal examinations included
      assessments of plaque, gingivitis, clinical attachment level, probing depth, and
      bleeding on probing. Serum cytokine levels also were analyzed. Gestational age at
      delivery was recorded, and the mothers were divided into a TPL or non-TPL group,
      and into a non-TPL-TB (term birth), non-TPL-PB, TPL-TB, or TPL-PB group,
      accordingly. RESULTS: Forty subjects were classified as TPL and 18 as TPL-PB.
      There were significant differences between the TPL and non-TPL subjects in
      several of the systemic and periodontal parameters and serum cytokine levels.
      Significant differences were observed between the TPL-TB and TPL-PB groups in the
      percentage of Tannerella forsythensis (Tf, formerly Bacteroides forsythus), and
      the serum interleukin (IL)-8 and IL-1beta levels. Significant negative
      correlations between the gestational age at delivery and several periodontal
      parameters and serum IL-8 and IL-1beta levels, and significant positive
      correlations between periodontal status and serum IL-8 and IL-1beta levels, were
      observed. CONCLUSIONS: The TPL women revealed worsened periodontal conditions and
      elevated serum IL-8 and IL-1beta levels compared to the non-TPL women. The
      elevated levels of serum IL-8 and IL-1beta could have affected the maintenance of
      the proper uterine-fetus relationship, resulting in premature uterine
      contractions.

PMID- 14974818
TI  - Anabolic potential of fibroblasts from chronically inflamed gingivae grown in a
      hyperglycemic culture medium in the presence or absence of insulin and nicotine.
AB  - BACKGROUND: Impaired fibroblast function due to hyperglycemia shows reversal in
      response to insulin. The aim of this investigation was to use a hyperglycemic
      cell-culture model to study the anabolic products of androgen metabolism in
      fibroblasts in response to insulin and nicotine. METHODS: Human gingival
      fibroblasts were derived from chronically inflamed gingivae of six nondiabetic
      periodontal patients with no history of smoking. Six cell lines were established
      in monolayer culture in 24 well multiwell plates, and duplicate incubations were
      performed with each cell line for all three experiments. Eagle's minimum
      essential medium was used in a range of individual experiments, with radiolabeled
      testosterone as substrate, in the presence or absence of (1) glucose (1 to 4,000
      microg/ml); (2) insulin (1 to 100 microg/ml) independently; (3) an effective
      concentration of glucose (500 microg/ml) with serial concentrations of insulin (1
      to 100 microg/ml); and (4) effective concentrations of nicotine (250 microg/ml),
      glucose, and their combinations in response to insulin (5 microg/ml). The
      controls contained no agents other than the radiolabeled substrate. At the end of
      a 24-hour incubation period, the medium was solvent extracted with ethyl acetate,
      and androgen metabolites were separated by thin-layer chromatography and were
      quantified using a radioisotope scanner. RESULTS: The androgen substrate 14C
      testosterone was metabolized mainly to 5alpha-dihydrotestosterone (DHT) and 4
      androstenedione. (1) Glucose at a concentration of 500 microg/ml reduced yields
      of DHT by 36% (n = 6; P < 0.01). (2) Insulin caused a small but significant
      inhibition of DHT in normoglycemic cells. (3) Serial concentrations of insulin
      significantly counteracted the inhibitory effects of glucose on the yields of DHT
      (n = 6; P < 0.01). (4) The independent inhibitory effects of nicotine and glucose
      on metabolic yields of DHT were marginally more pronounced in combination but
      significantly overcome in the presence of insulin. CONCLUSION: Human gingival
      fibroblasts obtained from chronically inflamed tissue of nondiabetic patients
      demonstrated that the inhibitory effects of glucose and nicotine on androgen
      metabolism can be overcome by insulin, in varying degrees.

PMID- 14974819
TI  - Blood test values and Community Periodontal Index scores in medical checkup
      recipients.
AB  - BACKGROUND: We examined the blood test values of people who received general
      medical checkups and their Community Periodontal Index (CPI) score. METHODS: A
      total of 7,452 persons (5,742 males and 1,710 females), who had general medical
      and dental checkups, were the subjects of the study. Many were people who worked
      for companies in and around Nagoya and their family members, ranging in age from
      16 to 80 years. The blood test in our study consisted of 37 items used in general
      blood tests. Partial-mouth recordings were used to measure CPI scores. The
      highest CPI score for each subject was used for analysis. Odds ratios and
      confidence interval values were obtained using the Mantel-Haenszel method to
      analyze the results. RESULTS: CPI scores of 3 and 4 were related to the test
      values of high-density-lipoprotein cholesterol, serum iron, white blood cell
      count, fasting blood sugar, glycosylated hemoglobin A1, glycosylated hemoglobin
      A1c, and C-reactive protein. CONCLUSION: Blood test values tended to show
      correlations with CPI scores, more clearly seen in males than in females.

PMID- 14974820
TI  - Vertical distance from the crest of bone to the height of the interproximal
      papilla between adjacent implants.
AB  - BACKGROUND: As patient demand increases for more natural restorations in the
      esthetic zone, clinicians must have the highest level of skill and knowledge to
      maintain or reform the interdental papilla between teeth, between implants and
      teeth, and between adjacent implants. To date, there are no reports that have
      measured the distance from the contact point to the bony crest between implants.
      One reason for this may be the fact that, with two adjacent implants, the contact
      point of the crown can be established at any distance from the gingival margin
      according to the restorative dentist's specifications. Therefore, in this study,
      the height of the soft tissue to the crest of bone was measured between two
      adjacent implants independent of the location of the contact point. The purpose
      of this study was to determine the range and average height of tissue between two
      adjacent implants. METHODS: A total of 136 interimplant papillary heights were
      examined in 33 patients by eight different examiners in five private dental
      offices. After administration of appropriate local anesthesia, a standardized
      periodontal probe was placed vertically from the height of the papilla to the
      crest of bone. The measurements were rounded off to the nearest millimeter.
      RESULTS: The mean height of papillary tissue between two adjacent implants was
      3.4 mm, with a range of 1 mm to 7 mm. CONCLUSIONS: Clinicians should proceed with
      great caution when placing two implants adjacent to each other in the esthetic
      zone. In most cases, only 2, 3, or 4 mm of soft tissue height (average 3.4 mm)
      can be expected to form over the interimplant crest of bone. These results showed
      that modification of treatment plans may be necessary when esthetics are critical
      for success.

PMID- 14974821
TI  - Periodontal health, salivary status, and metabolic control in children with type
      1 diabetes mellitus.
AB  - BACKGROUND: The aim of this study was to determine whether detectable periodontal
      destruction and alterations in the salivary status were present with duration of
      diabetes in children with type 1 insulin-dependent diabetes mellitus (type 1 DM)
      as compared to healthy controls. METHODS: Sixteen newly diagnosed children with
      DM (group 1), 16 children with type 1 DM of long duration (group 2), and 16
      healthy children (group 3) participated in the study. Periodontal health was
      assessed by plaque index, gingival index, bleeding on probing, and periodontal
      probing depths. The flow rate, pH, buffering capacity, and peroxidase activities
      of stimulated saliva were determined. The data were analyzed by Kruskall-Wallis,
      Student t test, and Pearson's correlation analysis. RESULTS: The mean values for
      fasting blood glucose levels for the diabetic groups were significantly higher
      than for the controls. The mean values for salivary buffering capacities and
      salivary pH from the diabetic groups were significantly lower than for the
      controls. The plaque index values for the diabetic groups were significantly
      higher than for the controls. The mean gingival index value for group 1 was
      significantly lower than for group 2. The mean periodontal probing depths for
      group 1 were similar to those of the non-DM controls, but the mean periodontal
      probing depths for group 2 were significantly greater than for both the non-DM
      controls and group 1. Group 1 had significantly greater bleeding on probing
      scores than did the other groups (P < 0.05). CONCLUSION: The glycemic status of
      the diabetic subjects affects the periodontal probing depths, salivary pH,
      buffering capacity, and peroxidase activity.

PMID- 14974822
TI  - Distribution of interleukin-1beta(+3954) and IL-1alpha(-889) genetic variations
      in a Thai population group.
AB  - BACKGROUND: The severe form of chronic periodontitis (CP) has been reported to be
      strongly associated with the presence of allele 2 of composite IL-1beta(+3954)
      and IL-1alpha(-889) genetic polymorphisms (genotype positive). However, other
      studies have reported conflicting findings, not only on the association between
      the composite IL-1 gene polymorphisms and CP, but also the link between IL-1 gene
      polymorphisms and aggressive periodontitis (AgP). These might have resulted from
      differences in ethnic background and disease entities. The aim of this study was
      to determine the distribution of IL-1beta(+3954) and IL-1alpha(-889) genetic
      polymorphisms in a group of Thai subjects based on their periodontal status,
      including CP, AgP, and healthy groups. METHODS: A total of 123 Thai subjects were
      clinically and radiographically assessed for their periodontal status. Blood
      samples were collected by fingerstick and adsorbed onto filter paper. The IL
      1beta(+3954) and IL-1alpha(-889) genotypes were performed by polymerase chain
      reaction, digested with restriction enzymes, and separated by gel
      electrophoresis. RESULTS: The distribution of allele 1 homozygous genotype was
      97.6% and 84.6% for IL-1beta(+3954) and IL-1alpha(-889), respectively. No allele
      2 homozygous genotype was detected in either of these two gene loci. Only 1.6% (2
      out of 123) of the subjects were genotype positive, which was too low to
      determine the association between the composite genotype of IL-1beta(+3954) and
      IL-1alpha(-889) and severe forms of periodontal disease. CONCLUSION: Genetic
      polymorphism of IL-1 genes in these two loci may not be useful in predicting the
      severity of periodontal disease in the Thai ethnic group.

PMID- 14974823
TI  - Alveolar bone response in an experimental model of renal failure and periodontal
      disease: a histomorphometric and histochemical study.
AB  - BACKGROUND: Chronic destructive periodontal disease is characterized by gingival
      inflammation, periodontal pocket formation, and bacterial plaque that lead to
      alveolar bone destruction. Polymorphonuclear neutrophil leukocytes (PMNs) are the
      first line of defense against infection caused by dental plaque bacteria. Renal
      patients present functional abnormalities of PMN, including impaired chemotaxis,
      phagocytosis, and intracellular killing of bacteria. In view of the above, the
      aim of this work was to evaluate the effect of renal failure on bone damaged by
      periodontal disease using histomorphometric and histochemical parameters.
      METHODS: Twenty male Wistar rats weighing 250 g were assigned to one of the
      following four groups: 1) control (no treatment); 2) renal failure (RF); 3)
      periodontal disease (PD); and 4) renal failure plus periodontal disease (RF+PD).
      All the animals were sacrificed 31 days after the onset of the experiment. Mesio
      distally oriented sections of the first lower molar were obtained for
      histomorphometric and histochemical evaluation. RESULTS: Total erosion, active
      erosion, and total number of tartrate-resistant acid phosphatase-positive (TRAP+)
      osteoclasts were found to be increased in the RF+PD group compared with the PD
      group. CONCLUSION: Our results demonstrate increased bone resorption in animals
      with untreated renal failure and periodontal disease, and thus indicate that the
      release of different factors by inflammatory cells is magnified, accelerating the
      progression of the disease in this animal model.

PMID- 14974824
TI  - Favorable healing following space creation in rhBMP-2-induced periodontal
      regeneration of horizontal circumferential defects in dogs with experimental
      periodontitis.
AB  - BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is believed
      to be capable of inducing periodontal regeneration. However, the risk of aberrant
      healing events, such as root resorption and ankylosis, has been reported. We
      hypothesized that implantation of BMP-containing carriers directly on the root
      planed surface may be the cause of unfavorable healing. The purpose of this study
      was to evaluate the influence of a 1 mm spacer membrane, which separated the
      rhBMP-2 in polymer-coated gelatin sponge (PGS) and the root surface, on
      periodontal regeneration of experimentally induced horizontal defects in dogs.
      METHODS: Horizontal circumferential periodontal defects were surgically created,
      and experimental periodontitis was induced in 72 maxillary and mandibular
      premolars of four male beagle dogs. The recipient sites of each quadrant
      received: 1) rhBMP-2/PGS (B group) (rhBMP-2 at 1.0 mg/ml, total implant volume/
      site approximately 7.2 microl) (n = 24); 2) rhBMP-2/PGS with a spacer membrane
      (PB group) (n = 24); and 3) physiological saline (PS)/PGS as a control (P group)
      (n = 24). One quadrant was left untreated. Dogs were sacrificed at 12 weeks post
      surgery, and healing was evaluated histologically. RESULTS: Both groups treated
      with rhBMP-2/PGS demonstrated enhanced new bone formation and connective tissue
      attachment with cementum regeneration when compared to the control group. Sites
      treated with rhBMP-2/PGS showed a greater degree of bone formation than sites
      treated with rhBMP-2/PGS and spacer membrane, although the latter sites showed no
      ankylosis. CONCLUSIONS: Implantation of rhBMP-2/PGS enhances bone formation and
      connective tissue attachment in horizontal circumferential defects. In addition,
      the use of a spacer membrane reduces the degree of bone formation, but minimizes
      ankylosis.

PMID- 14974825
TI  - Conversion from cyclosporin A to tacrolimus as a non-surgical alternative to
      reduce gingival enlargement: a preliminary case series.
AB  - BACKGROUND: Gingival enlargement (GE) is a frequent side effect that occurs in
      organ transplant recipients (OTR) after the administration of cyclosporin A
      (CsA). The availability of new drugs used to suppress graft rejection in OTR
      offers an opportunity to manage GE non-surgically. This preliminary case series
      aimed to analyze the effect of CsA withdrawal and its substitution by another
      immunosuppressant in OTR with severe GE. METHODS: Four organ transplant
      recipients who had received a liver or renal allograft were recruited for this
      study. All OTR had developed clinically severe CsA-induced GE. GE scores were
      assessed for each patient at baseline and at weeks 2, 4, 8, 12, 16, and 54
      following conversion to tacrolimus. Scaling and root planing were initially
      performed and repeated monthly during the first 6 months. Careful polishing of
      the teeth was carried out once every 2 weeks until month 6 and then monthly until
      month 12. Hygiene instructions and reinforcement to optimize oral hygiene were
      maintained throughout the study. RESULTS: The four patients showed a rapid
      decrease in their gingival symptoms and in the size of the gingivae. This change
      was clinically evident 8 weeks after conversion to tacrolimus. One year later,
      all the patients experienced GE regression, although some anatomic irregularities
      persisted in the interdental papillae of one of the patients. No adverse effects
      from tacrolimus were observed during the study except in one patient who
      presented headaches. CONCLUSION: It seems that CsA withdrawal and its conversion
      to tacrolimus in organ transplant recipients who develop severe gingival
      enlargement, together with an extensive plaque control program, provide an
      effective means to control/eliminate gingival hyperplasia, with minimal risk of
      graft dysfunction.

PMID- 14974826
TI  - Re: Use of orthodontic treatment as an aid to third molar extraction: A method
      for prevention of mandibular nerve injury and improved periodontal status. Hirsch
      A, Shteiman S, Boyan BD, Schwartz Z (2003;74:887-892).

PMID- 14974827
TI  - President's address. 2020 Vision for periodontics.

PMID- 14974828
TI  - Pediatric aphakic glaucoma.

PMID- 14974829
TI  - Primary megalocornea: clinical features for differentiation from infantile
      glaucoma.
AB  - PURPOSE: To describe the ocular findings in megalocornea to assist in its
      differentiation from infantile glaucoma in the evaluation of children with
      abnormally enlarged corneas. METHODS: The clinical findings of 4 boys found to
      have megalocornea following referral for evaluation of large corneas and
      suspected glaucoma were reviewed. RESULTS: Three of the 4 patients had
      photophobia. Clear and enlarged corneas were observed associated with deep
      anterior chambers, posterior bowing of the irides, and normal intraocular
      pressures (IOPs) in all eyes. Transillumination of the irides was found in 6 of 8
      eyes and pigment dispersion was seen in 4 of 8 eyes. Pigment dispersion appeared
      to be acquired over time, and the youngest patient in this series who had pigment
      dispersion detected on slit-lamp examination was 15 years; the youngest patient
      with the condition detected on gonioscopy was 8 years. No breaks in Descemet's
      membrane were present. Family history obtained from 3 of the 4 patients revealed
      evidence of sex-linked recessive inheritance. These findings are distinct from
      the clinical features of infantile glaucoma characterized by elevated IOP, breaks
      in Descemet's membrane, corneal edema, a generally flat iris profile, less
      pronounced enlargement of the anterior segment, the absence of iris
      transillumination and pigment dispersion, and autosomal recessive inheritance.
      Three patients had corneal size asymmetry, a finding that has not been previously
      reported. CONCLUSION: Hereditary megalocornea has defining clinical findings that
      help to identify and differentiate it from other causes of enlarged corneas.
      Asymmetry in corneal size does not preclude its diagnosis.

PMID- 14974830
TI  - Atypical presentations of retinoblastoma.
AB  - PURPOSE: To study the atypical presentations of retinoblastoma in our
      institution. METHOD: Retrospective, clinical study. RESULTS: A total of 392 cases
      of retinoblastoma were reviewed; 72.2% of the patients had leukocoria, 13% had
      proptosis, 10% had strabismus, 1.5% were asymptomatic (detected on screening),
      and 3.3% had atypical presentations. Fourteen different atypical findings were
      observed including endophthalmitis (0.76%), secondary glaucoma (0.76%), uveitis
      (0.5%), corneal edema (0.5%), phthisis bulbi (0.5%), orbital cellulitis (0.5%),
      cataract (0.25%), pseudohypopyon (0.25%), iris nodules (0.25%), hyphema (0.25%),
      iris neovascularization (0.25%), microphthalmos (0.25%), exposure keratopathy
      (0.25%), and corneal blood staining (0.25%). All of the patients had Reese
      Ellsworth grade V disease. On histopathology, invasion of neighboring structures
      was seen in 10 patients. All patients underwent enucleation with adjuvant
      radiotherapy, chemotherapy, or both. CONCLUSIONS: Retinoblastoma can mimic any
      orbital or ocular pathology. Atypical presentations of retinoblastomas are
      usually associated with advanced disease. The possibility of ocular tumor should
      be entertained whenever there is an unusual presentation that is unresponsive to
      the usual therapy. Ultrasonography and computed tomography should be performed in
      all such patients, especially if the posterior segment is not visible.

PMID- 14974831
TI  - Vertical diplopia following peribulbar anesthesia: the role of hyaluronidase.
AB  - PURPOSE: To estimate the incidence of vertical diplopia following peribulbar
      anesthesia in otherwise uncomplicated cataract surgery and to establish whether
      the use of hyaluronidase in the peribulbar injection mixture affected the
      likelihood of this complication. METHODS: Nine hundred forty consecutive
      phacoemulsification procedures using peribulbar anesthesia were retrospectively
      reviewed to identify cases of postoperative vertical diplopia. Case notes were
      reviewed to establish the nature and timing of the onset of diplopia, the
      anesthetic technique, and whether hyaluronidase was used. The patterns of
      progression as demonstrated by serial Hess charts were compared. RESULTS: There
      were 6 cases of vertical diplopia (incidence, 0.64%). All showed an immediate
      postoperative hypertropia in the injected eye changing during a 4- to 6-week
      period to hypotropia with restriction of upgaze. All applications of anesthesia
      were administered by consultant anesthetists, associate specialists, or residents
      under their direct supervision using 25-mm, 25-gauge needles with 2% lidocaine.
      Hyaluronidase was included in the injection mixture for 435 (46%) of the cases
      and was not included for 505 (54%) of the cases. All 6 cases of vertical diplopia
      occurred in the group in which hyaluronidase was not used, which has a
      significant association (chi-square test, 5.22; P = .023). CONCLUSION:
      Hyaluronidase should be included in peribulbar anesthetics to reduce the risk of
      postoperative vertical diplopia.

PMID- 14974832
TI  - Screening for retinopathy of prematurity: results of a retrospective 3-year study
      of 502 infants.
AB  - PURPOSE: To describe the surveillance, results of screening, and treatment of
      retinopathy of prematurity (ROP) in a university hospital setting in southeast
      France. PATIENTS AND METHODS: Five hundred two premature infants were included in
      the screening protocol between January 1997 and December 1999. Criteria for
      inclusion in the study were a gestational age of 32 weeks or younger, a birth
      weight of less than 1,501 g, or both. The first fundus examination was performed
      between 4 and 6 weeks of life. Thereafter, fundus examination was performed in
      the absence of ROP every 2 weeks until complete retinal vasculature developed,
      gestational age of 50 weeks, or death. Examination was weekly in cases of
      retinopathy, biweekly if progression was ascertained, and less frequent only if
      regression was evident. Hospital records were reviewed to assess the presence or
      absence and eventual degree of ROP. RESULTS: Stage 1 was observed in 32 infants,
      and stage 2 in 11 infants; all of these cases regressed. Three cases of bilateral
      stage 3 (two threshold and one prethreshold) disease underwent diode laser
      peripheral retinal ablation and regressed. One infant with bilateral stage 3
      disease who underwent peripheral cryoablative surgery progressed to stage 4A in
      one eye and 4B in the other eye and then underwent scleral buckling surgery in
      the second eye. CONCLUSIONS: Despite survival increasing with improved neonatal
      intensive care, the incidence of ROP does not appear to be increasing. In our
      center, the incidence appears to be lower than previously reported.

PMID- 14974833
TI  - Changes in astigmatism after congenital cataract surgery and foldable intraocular
      lens implantation.
AB  - PURPOSE: To evaluate the changes in astigmatism after cataract extraction and
      implantation of a foldable intraocular lens (IOL) in children. Only eyes with
      astigmatism of 3.0 D or more were included in the study. METHODS: The charts of
      children who had undergone surgery for nontraumatic cataract using a foldable IOL
      were retrospectively reviewed. In 13 eyes with astigmatism of 3.0 D or more, the
      refraction was tested and recorded at 1 week, 3 months, and 5 months
      postoperatively. A paired t test was used to compare the variables. RESULTS: Mean
      astigmatism 1 week postoperatively was 4.7 +/- 1.9 D (range, 3.0-10.0 D).
      Thereafter, the astigmatic component of the refractive error underwent a
      spontaneous steady decline, reaching a mean value of 0.9 +/- 0.9 D (range, 0-2.25
      D) 5 months after surgery. The difference between the mean values at 1 week and 5
      months was statistically significant (P < .0001). CONCLUSION: Children who
      underwent congenital cataract surgery and IOL implantation showed a significant
      spontaneous reduction in astigmatism postoperatively.

PMID- 14974834
TI  - Peripheral and central visual fields in 11-year-old children who had been born
      prematurely and at term.
AB  - PURPOSE: To examine the peripheral and central visual fields in children who had
      been born prematurely and at term. METHODS: Four groups of 11-year-old children
      were examined: group 1 included 24 children who had been born at term (control
      group); group 2 included 20 children who had been born prematurely without ROP;
      group 3 included 22 children who had been born prematurely with untreated ROP
      (stages 2 and 3); and group 4 included 21 children who had been born prematurely
      and underwent cryotreatment for severe ROP. Their peripheral visual fields were
      examined with Goldmann perimetry. Static high-pass resolution perimetry was used
      to evaluate their central visual fields within 30 degrees. RESULTS: The
      peripheral visual fields were constricted in children who had undergone
      cryotreatment (group 4), as compared with the other groups (1 to 3). We found no
      difference between the groups of children who had been born prematurely with or
      without ROP (groups 2 and 3) and the control group. The function of the central
      visual fields, expressed as neural capacity, was reduced in the children who had
      been born prematurely compared with the controls, significantly in their left
      eyes only. The children who underwent cryotreament did not differ from the other
      children who had been born prematurely in this respect. CONCLUSIONS: The
      peripheral visual fields were constricted in children who had undergone
      cryotreatment. It is uncertain whether this was caused by the treatment or by
      severe ROP. The central visual fields showed a tendency of reduced neural
      capacity in the children who had been born prematurely, reflecting a reduced
      density of retinocortical neural channels. However, this was not related to ROP
      or cryotreatment.

PMID- 14974835
TI  - Medulloepithelioma of the optic nerve.

PMID- 14974836
TI  - Large pedunculated congenital corneal dermoid in association with eyelid
      coloboma.

PMID- 14974837
TI  - Conjunctival melanoma in a child.

PMID- 14974838
TI  - Spontaneous rupture of the anterior lens capsule combined with macular hole in a
      child with Alport's syndrome.

PMID- 14974839
TI  - E. P. Pope Memorial Award to Dr. Terry F. McElwain.

PMID- 14974840
TI  - Diagnosis of West Nile virus infection in horses.
AB  - The North American West Nile virus (WNV) epizootic, which began in 1999, has
      caused significant morbidity and mortality in horses. Because experimental
      infection has failed to consistently produce encephalitis in inoculated horses,
      investigation of naturally occurring cases was used to optimize strategies for
      diagnosis of this disease. Although WNV RNA could be detected by reverse
      transcriptase-polymerase chain reaction (RT-PCR) performed on whole blood
      collected from both clinically affected horses and unaffected herdmates, the
      diagnostic sensitivity of this approach was low compared with IgM-capture enzyme
      linked immunosorbent assay. In addition, it was observed that 18.5% of herdmates
      of clinically ill horses seroconverted to WNV yet exhibited no overt clinical
      signs of WNV encephalitis. West Nile viral RNA was detected in neural tissue of
      46 of 64 dead horses that were suspected of having WNV encephalitis. Some of
      these animals were IgM negative or had not been tested serologically. A primary
      cause of death other than WNV encephalitis was identified in 15 of the 64 cases,
      whereas the final diagnosis for 3 of these cases remains unresolved. Quantitative
      RT-PCR analysis of neural tissue from WNV RNA-positive horses demonstrated that
      the medulla contained the highest mean concentration of viral RNA and that WNV
      RNA could be detected in samples extracted from formalin-fixed neural tissue. A
      comparison of WNV RT-PCR amplification strategies found that nested RT-PCR
      improved diagnostic sensitivity only slightly over a single round of
      amplification and that a quantitative (TaqMan) assay had sensitivity and
      specificity that were equivalent to those of nested amplification.

PMID- 14974841
TI  - A simulation model of intraherd transmission of foot and mouth disease with
      reference to disease spread before and after clinical diagnosis.
AB  - Intraherd transmission of foot and mouth disease virus (FMDV) was examined using
      a simulation model for a hypothetical 1,000-cow dairy, assuming clinical
      diagnosis was made when at least 1% (10 cows) or 5% (50 cows) had clinical signs
      of FMD, I index case cow, and transition state distributions for the latent,
      subclinically infectious, and clinically infectious periods of FMD calculated
      from published data. Estimates assumed for the number of animal-to-animal
      contacts (k) adequate for transmission ranged from 0.6 to 9.0 per hour (13.7
      216.0 per day). A total of 40,000 iterations (5,000 for each scenario, assessing
      4 adequate contact rates and 2 detection criteria) were run. The model predicted
      that FMD would not be diagnosed in the herd until 10.0-13.5 days after the index
      case cow had become infected, at which time between 65% and 97% of the cows (646
      967 cows) to nearly 100% (978-996 cows) would already have become infected with
      the virus, if the number of cows showing clinical signs of FMD at the time of
      diagnosis were 10 or 50, respectively. At the time of diagnosis, the simulated
      number of infectious cattle varied substantially from 82-472 to 476-537 cows,
      depending on adequate contact rate and whether the diagnosis was made when 10 or
      50 animals were showing clinical signs, respectively. The simulated number of
      infectious cows increased rapidly during the first few days after diagnosis. In
      the scenario where at least 10 cows showing clinical signs was necessary before a
      clinical diagnosis was made, each day after diagnosis, the number of infectious
      animals increased by nearly 100 to more than 200 cases per day up to day 5,
      assuming 0.57-9.0 animal-to-animal contacts per hour, respectively. Results
      obtained when it was assumed that at least 50 clinical cases were present at the
      time of diagnosis showed smaller relative increases because nearly one-half of
      the herd was projected to be infected at the time of diagnosis. From these
      results, it is clear that once an individual in a herd becomes infected with
      FMDV, herd infectivity is not static, rather it accelerates as would be expected
      as long as there are sufficient susceptible animals to sustain the increasing
      transmission rate, after which time the rate at which new infections occurs will
      diminish. Results indicate that biosecurity strategies aimed at minimizing both
      intraherd and interherd contact will be critical in minimizing the spread of FMD
      before the initial diagnosis is made. In addition, simulations suggest that very
      early clinical diagnosis of FMD and effective isolation or depopulation and
      disposal will be critical in limiting the number of infectious animals capable of
      transmitting the virus to other herds and thus in timely control of an epidemic.
      Early diagnosis will rely on early virus detection from animals in the
      preclinical phase of infection, rather than waiting for clinical signs to
      manifest in sufficient numbers to be noticed and to warrant investigation.

PMID- 14974842
TI  - Evaluation of an in vitro blood-based assay to detect production of interferon
      gamma by Mycobacterium bovis-infected white-tailed deer (Odocoileus virginianus).
AB  - Tuberculosis due to Mycobacterium bovis in captive Cervidae was identified as an
      important disease in the United States in 1990 and prompted the addition of
      captive Cervidae to the USDA Uniform Methods and Rules for eradication of bovine
      tuberculosis. As well, M. bovis infection was identified in free-ranging white
      tailed deer in northeast Michigan in 1995. Tuberculosis in both captive and free
      ranging Cervidae represents a serious challenge to the eradication of M. bovis
      infection from the United States. Currently, the only approved antemortem tests
      for tuberculosis in Cervidae are the intradermal tuberculin skin test and the
      blood tuberculosis test (BTB). At present, the BTB is not available in North
      America. Tuberculin skin testing of Cervidae is time-consuming and involves
      repeated animal handling and risk of injury to animals and humans. This study
      evaluated the potential of a new blood-based assay for tuberculosis in Cervidae
      that would decrease animal handling, stress, and losses due to injury. In
      addition, a blood-based assay could provide a more rapid diagnosis. Twenty 6-9
      month-old white-tailed deer, male and female, were experimentally inoculated by
      instillation of 300 colony-forming units of M. bovis in the tonsillar crypts.
      Seven, age-matched uninfected deer served as controls. Blood was collected on
      days 90, 126, 158, 180, 210, 238, 263, and 307 after inoculation and was analyzed
      for the production of interferon-gamma (IFN-gamma) in response to incubation with
      M. bovis purified protein derivative (PPDb), M. avium PPDa, pokeweed mitogen
      (PWM), or media alone. Production of IFN-gamma in response to PPDb was
      significantly greater (P < 0.05) at all time points in samples from M. bovis
      infected deer as compared with uninfected control deer, whereas IFN-gamma
      production to PWM did not differ significantly between infected and control deer.
      Measurement of IFN-gamma production to PPDb may serve as a useful assay for the
      antemortem diagnosis of tuberculosis in Cervidae.

PMID- 14974843
TI  - A simple, rapid, and effective method for the extraction of Mycobacterium
      paratuberculosis DNA from fecal samples for polymerase chain reaction.
AB  - Diagnosis of paratuberculosis (Johne's disease) is stymied by the lack of 1
      diagnostic tool that can be used to detect both subclinically and clinically
      infected animals. At present, fecal culture remains the single diagnostic test
      that can detect infection in both disease states provided the animals actively
      shed Mycobacterium paratuberculosis in their feces. Yet, fecal culture has a
      disadvantage associated with the protracted incubation period of 8-16 weeks
      before results are available. Detection of nucleic acids specific to M.
      paratuberculosis in fecal samples is a technique that can circumvent the culture
      method. This study describes a rapid, simple, and effective method to extract DNA
      from fecal samples and modification of a polymerase chain reaction assay for
      optimal sensitivity of detection. An evaluation of 1,000 well-characterized fecal
      samples was performed by the Colorado Department of Agriculture (Denver, CO) and
      the National Animal Disease Center (Ames, IA) to determine the sensitivity,
      specificity, and reproducibility of the new method. Results from this study show
      that the sensitivity of detection was highly dependent on the load of bacteria in
      the fecal sample with 81% detection of samples containing >70 colony-forming
      units (cfu)/g of feces and a 45% detection rate for samples containing less than
      1 cfu/g. Similarly, reproducibility of the technique between the 2 laboratories
      (n = 250 samples) was much higher (75%) for the fecal samples containing high
      levels of M. paratuberculosis and reduced to 25% for samples with less than 1
      cfu/g. An overall specificity of 83% was obtained for known negative samples. The
      method described here is rapid, simple, and inexpensive compared with other
      techniques. In addition, this method can detect animals that are shedding less
      than 1 cfu/g.

PMID- 14974844
TI  - Effects of prevalence and testing by enzyme-linked immunosorbent assay and fecal
      culture on the risk of introduction of Mycobacterium avium subsp.
      paratuberculosis-infected cows into dairy herds.
AB  - A stochastic simulation model was developed to assess the risk of introduction of
      Mycobacterium avium subsp. paratuberculosis infection into a dairy herd through
      purchase of female replacement cattle. The effects of infection prevalence in the
      source herd(s), number of females purchased, and testing by enzyme-linked
      immunosorbent assay (ELISA) alone or ELISA and fecal culture as risk mitigation
      strategies were evaluated. Decisions about negative test results were made on a
      lot and individual basis. A hypothetical dairy herd, free from M. a.
      paratuberculosis, which replaced 1 lot (10, 30, or 100) of cows per year, was
      considered. Probability distributions were specified for the sensitivities and
      specificities of ELISA and fecal culture, the proportion of infected herds and
      within-herd prevalence for randomly selected replacement source herds (high
      prevalence) and herds in level 2 (medium prevalence) and level 3 (low prevalence)
      of the Voluntary Johne's Disease Herd Status Program (VJDHSP). Simulation results
      predicted that 1-56% of the lots had at least 1 M. a. paratuberculosis-infected
      cow. Assuming that ELISA sensitivity was 25%, simulation results showed on a lot
      basis that between 0.4% and 18% and between 0.1% and 9% were predicted to have at
      least 1 infected cow not detected by ELISA and by a combination of ELISA and
      fecal culture, respectively. On an individual cow basis, between 0.1% and 8.3% of
      ELISA-negative cattle in ELISA-positive lots were estimated to be infected. In
      both the lot and individual analyses, the probability of nondetection increased
      with larger lot sizes and greater prevalence. Sensitivity analysis indicated that
      the effect of a lower ELISA sensitivity (10%) was a variable decrease in mean
      detection probabilities for all combinations of prevalence and lot size. The
      benefit of testing introduced cattle with ELISA alone or in combination with
      fecal culture was found to be minimal if cows were purchased from known, low
      prevalence (level 3) herds. The value of testing by ELISA alone or in combination
      with fecal culture was greatest in high-prevalence herds for all lot sizes.
      Testing of random-source cattle, bought as herd replacements, can partially
      mitigate the risk of introduction of M. a. paratuberculosis but not as well as by
      using low-prevalence source herds (level-3 VJDHSP), with or without testing.

PMID- 14974845
TI  - Laboratory diagnosis of canine GM2-gangliosidosis using blood and cerebrospinal
      fluid.
AB  - In the present study, laboratory techniques were used to diagnose canine GM2
      gangliosidosis using blood and cerebrospinal fluid (CSF) that can be collected
      noninvasively from living individuals. Lysosomal acid beta-hexosaminidase (Hex)
      was measured spectrofluorometrically using 4-methylumbelliferyl N-acetyl-beta-D
      glucosaminide and 4-methylumbelliferyl 7-(6-sulfo-2-acetamido-2-deoxy-beta-D
      glucopyranoside) as substrates. Main isoenzymes A and B of Hex in leukocytes were
      also analyzed using cellulose acetate membrane electrophoresis. GM2-ganglioside
      in CSF was detected and determined quantitatively by using thin-layer
      chromatography/enzyme-immunostaining method with anti-GM2-ganglioside antibody.
      In normal dogs, Hex activities could be determined in leukocytes, serum, and CSF
      and the total activities were markedly reduced in all the enzyme sources in a dog
      with Sandhoff disease. Electrophoresis of a leukocyte lysate from a normal dog
      showed that the Hex A and Hex B were not separated distinctively with formation
      of a broad band, whereas there were no bands in electrophoresis of a lysate from
      a dog with Sandhoff disease, showing a deficiency in the total enzyme activity.
      GM2-ganglioside could be detected and determined quantitatively in as little as
      100 microl of canine CSE GM2-ganglioside in CSF in a dog with Sandhoff disease
      increased to 46 times the normal level. In conclusion, the methods in the present
      study are useful for diagnosis of canine GM2-gangliosidosis. These techniques
      enable definitive and early diagnosis of canine GM2-gangliosidosis even if
      tissues and organs cannot be obtained.

PMID- 14974846
TI  - A comparison of virus isolation, polymerase chain reaction, immunohistochemistry,
      and in situ hybridization for the detection of porcine circovirus 2 and porcine
      parvovirus in experimentally and naturally coinfected pigs.
AB  - Virus isolation, polymerase chain reaction (PCR), immunohistochemistry, and in
      situ hybridization were compared for the detection of porcine circovirus 2 (PCV2)
      and porcine parvovirus (PPV) from experimentally and naturally coinfected pigs.
      All coinfected pigs developed postweaning multisystemic wasting syndrome (PMWS),
      characterized by sudden onset of depression and anorexia. Microscopically,
      granulomatous inflammation with intracytoplasmic inclusion bodies was present in
      lymph node from all coinfected pigs at 32 days postinoculation. Of the 200
      tissues from 20 experimentally coinfected pigs evaluated, 99 and 58 tissues were
      positive for PCV2 and PPV, respectively, by 4 techniques. Virus isolation, PCR,
      immunohistochemistry, and in situ hybridization identified PCV2 infection in 137,
      148, 103, and 129 tissues and PPV infection in 107, 132, 59, and 94 tissues. Of
      the 200 tissues from 20 naturally coinfected pigs evaluated, 109 and 45 tissues
      were positive for PCV2 and PPV, respectively, by 4 techniques. Virus isolation,
      PCR, immunohistochemistry, and in situ hybridization identified PCV2 infection in
      144, 155, 113, and 139 tissues and PPV infection in 93, 109, 45, and 82 tissues.
      Because the characteristic microscopic lesions are important criteria for the
      diagnosis of clinical PMWS, immunohistochemistry and in situ hybridization for
      the detection of PCV2 and PPV in formalin-fixed, paraffin-embedded tissues
      provide confirmation of a histopathological diagnosis of PMWS.

PMID- 14974847
TI  - Application and evaluation of RT-PCR-ELISA for the nucleoprotein and RT-PCR for
      detection of low-pathogenic H5 and H7 subtypes of avian influenza virus.
AB  - Three 1-tube Reverse Transcriptase Polymerase Chain Reactions (RT-PCR) directed
      against the genes encoding the nucleoprotein (NP) and the H5 and H7 hemagglutinin
      (HA) gene, respectively, were used for detection of avian influenza virus (AIV)
      in various specimens. A total of 1,040 samples originating from chickens
      experimentally infected with 2 different low pathogenic avian influenza viruses,
      from domestic ducks and from wild aquatic birds were examined. The outcome of 1)
      the universal AIV RT-PCR including a PCR-enzyme-linked immunosorbent assay
      (ELISA) procedure directed against NP (NP RT-PCR-ELISA) and 2) the subtype
      specific RT-PCR for H5 and H7 were compared to the results obtained by
      inoculation of the same specimens into the allantoic cavity of embryonated
      specific pathogen free (SPF) hen's eggs. Using inoculation in SPF fowl eggs as
      standard the sensitivity of the NP RT-PCR-ELISA and the RT-PCR for H5 or H7 was
      91% and 94%, and the corresponding specificity 98% and 96%. In comparison with
      inoculation into eggs an additional of 9 samples were positive by NP RT-PCR-ELISA
      and 13 samples were positive by RT-PCR for one of the HA subtypes. Hence, the 3
      RT-PCR procedures described are fast, sensitive and specific for detecting AIV
      and subtyping H5 and H7 and they are obvious alternatives when testing large
      numbers of samples.

PMID- 14974848
TI  - Transmission of transmissible mink encephalopathy to raccoons (Procyon lotor) by
      intracerebral inoculation.
AB  - To determine the transmissibility of transmissible mink encephalopathy (TME)
      agent to raccoons and to provide information about clinical course, lesions, and
      suitability of currently used diagnostic procedures for detection of
      transmissible spongiform encephalopathies (TSEs) in raccoons, 4 raccoon kits were
      inoculated intracerebrally with a brain suspension from mink experimentally
      infected with TME. One uninoculated raccoon kit served as a control. All 4
      animals in the TME-inoculated group showed clinical signs of neurologic disorder
      and were euthanized between 21 and 23 weeks postinoculation (PI). Necropsy
      examinations revealed no gross lesions. Spongiform encephalopathy was observed by
      light microscopy, and the presence of protease-resistant prion protein (PrPres)
      was detected by immunohistochemistry and Western blot techniques. Scrapie
      associated fibrils were observed by negative-stain electron microscopy in the
      brains of 3 of the 4 inoculated raccoons. These findings confirm that TME is
      experimentally transmissible to raccoons and that diagnostic techniques currently
      used for TSE in livestock detect prion protein in raccoon tissue. According to
      previously published data, the incubation period of sheep scrapie in raccoons is
      2 years, whereas chronic wasting disease (CWD) had not shown transmission after 3
      years of observation. Because incubation periods for the 3 US TSEs (scrapie, TME,
      and CWD) in raccoons appear to be markedly different, it may be possible to use
      raccoons for differentiating unknown TSE agents. Retrospective genotyping of
      raccoons using frozen spleens showed that the raccoon PrP gene is identical to
      the mink gene at codons 179 and 224. Further studies, such as the incubation
      periods of bovine spongiform encephalopathy and other isolates of scrapie, CWD,
      and TME in raccoons, are needed before the model can be further characterized for
      differentiation of TSE agents.

PMID- 14974849
TI  - West Nile virus meningoencephalitis in a Suri alpaca and Suffolk ewe.
AB  - The first confirmed cases of West Nile virus (WNV) in the Western Hemisphere were
      reported in the state of New York in 1999. Since then, the virus has spread
      throughout the eastern and central United States and continues to extend
      westward. This report describes clinical signs and microscopic lesions associated
      with WNV infection in a Suffolk ewe and an alpaca, 2 species in which the disease
      has not been reported previously. In late August 2002, a 4.5-year-old female
      alpaca developed an acute onset of clinical signs characterized by torticollis,
      hyperesthesia, ataxia, recumbency, and altered mentation. The animal died 3.5
      days after the onset of clinical signs. Microscopic examination of the brain
      revealed a mild to moderate, diffuse, lymphoplasmacytic meningoencephalitis. In
      early September 2002, a 3-year-old Suffolk ewe developed a rapidly progressive
      illness characterized by ataxia and convulsions. The apparent duration from onset
      of clinical signs until death was less than 8 hours. The ewe had a moderate,
      diffuse, lymphoplasmacytic meningoencephalitis with focal gliosis. Reverse
      transcription-polymerase chain reaction assays and immunohistochemistry on the
      brain were positive for WNV in both animals. These cases demonstrate that WNV is
      capable of causing sporadic, fatal, nonsuppurative meningoencephalitis in alpacas
      and sheep.

PMID- 14974850
TI  - Detection and nucleotide sequencing of a DNA-packaging protein gene of equine
      gammaherpesviruses.
AB  - In previous studies, novel putative viral pathogens designated that asinine
      herpesvirus 4 (AsHV4) and asinine herpesvirus 5 (AsHV5) were associated with
      fatal interstitial pneumonia in donkeys (Equus asinus). Nucleotide sequence
      analysis of a portion of the DNA polymerase gene identified these putative
      pathogens as herpesviruses and possibly as members of the Gammaherpesvirinae
      subfamily. Although similar to equine herpesvirus 2 (EHV2) and equine herpesvirus
      5 (EHV5), sequence diversity was observed among the detected viruses. In this
      study, novel sequence is reported for a DNA-packaging protein gene of EHV5 plus
      AsHV4, AsHV5, and a newly described putative pathogen herein designated asinine
      herpesvirus 6 (AsHV6). Phylogenetic analysis of these sequences suggested that
      the equine gammaherpesviruses may form a separate clade within the
      Gammaherpesvirinae subfamily. Based on the sequence of EHV2 and the novel
      sequences reported in this study, a PCR assay was developed to detect equine
      gammaherpesviruses. Products of the predicted size were produced after
      amplification of DNA from EHV2, EHV5, AsHV4, AsHV5, and AsHV6. This nonnested
      assay was shown to consistently amplify approximately 10 genomic copies of EHV2.
      Amplification products were not produced from DNA template of other alpha- and
      gammaherpesviruses. Because the role of gammaherpesviruses has not been well
      defined in equine disease, it is envisioned that a single, sensitive PCR assay to
      detect these potential pathogens will facilitate further assessment of their role
      in disease.

PMID- 14974851
TI  - Detection of equine herpesvirus 3 in equine skin lesions by polymerase chain
      reaction.
AB  - During a recent breeding season, ulcerative, pustular skin lesions were observed
      on the external genitalia of 2 mares and 1 stallion within a small herd. Based on
      the location and description of the skin lesions plus the clinical history,
      equine coital exanthema, caused by equine herpesvirus 3 (EHV3), was the primary
      differential diagnosis. Scrapings of skin lesions from the perineum of 2 mares
      were submitted for diagnostic evaluation. Virus isolation was attempted by
      inoculation of several cell lines of equine origin, but no cytopathic agent was
      detected. The skin scrapings were processed for DNA extraction, and polymerase
      chain reaction (PCR) amplification was performed for herpesvirus DNA polymerase
      and DNA-packaging protein (terminase) genes using nested, degenerate primers
      targeted to conserved regions of the herpesvirus genome. Products of the expected
      sizes were generated for both assays, and subsequent nucleotide sequencing of the
      amplification products established that EHV3 had been detected in DNA extracted
      from the skin lesions. Detection of EHV3 was confirmed using an EHV3-specific PCR
      assay targeted to the gC gene. Using the novel EHV3 nucleotide sequence
      identified in this report, a sensitive and specific PCR assay targeted to the
      highly conserved DNA polymerase gene was developed.

PMID- 14974852
TI  - Escherichia coli O157:H7 in the gallbladders of experimentally infected calves.
AB  - Fifteen weaned calves (age 89-141 days) were treated with dexamethasone (0.25
      mg/kg, IV) for 3 days before, the day of, and the day after inoculation with 10
      colony-forming units of either Escherichia coli O157:H7 (strain 86-24, which
      produces Shiga toxin 2 and intimin; n = 13) or nonpathogenic E. coli (strain 123,
      which does not produce Shiga toxin or intimin; n = 2). All calves were necropsied
      4 days after inoculation. Histologic lesions of attaching and effacing bacteria
      were observed in the large intestine (12/13) and in the gallbladder mucosa (5/13)
      of calves inoculated with E. coli 86-24. Cholecystitis was present in 12 of 13
      calves that received E. coli 86-24. Inoculum bacteria were recovered from the
      distal colons or feces (13/13) and gallbladders (3/4) of calves inoculated with
      86-24.

PMID- 14974853
TI  - Localized cutaneous infection with Francisella tularensis resembling
      ulceroglandular tularemia in a cat.
AB  - A chronically draining subcutaneous mass was removed from the ventral cervical
      region of a 6-year-old spayed female Domestic Shorthair cat. The histopathologic
      diagnosis was severe locally extensive pyogranulomatous and necrotizing
      cellulitis. Bacterial culture yielded Francisella tularensis subsp. tularensis as
      the causative agent. Immunohistochemical evaluation of sections for F. tularensis
      was negative. One year later, the cat was euthanized because of progressive
      lethargy found to be due to hypertrophic cardiomyopathy with pulmonary
      thromboembolism. No evidence of cutaneous or systemic infection by F. tularensis
      was found at necropsy. This case appears to be a localized form of tularemia
      resembling the ulceroglandular form of tularemia in humans and suggests that
      bacterial culture may be more sensitive than immunohistochemistry in detecting
      organisms in cases of localized F. tularensis infection.

PMID- 14974854
TI  - Comparison of a commercial enzyme-linked immunosorbent assay with
      hemagglutination inhibition assay for serodiagnosis of swine influenza virus
      (H1N1) infection.
AB  - A commercial indirect swine influenza virus (SIV) H1N1 enzyme-linked
      immunosorbent assay (ELISA) was compared with the hemagglutination inhibition
      (HI) assay by testing 72 samples from experimentally infected pigs and 780 field
      samples of undefined SIV status. The HI assay was performed using SIV isolates
      A/Swine/IA/73 for H1N1 and A/Swine/IA/8548-1/98 for H3N2. The ELISA used an SIV
      isolated in 1988. The results showed that HI and ELISA detected an antibody in 11
      and 6, respectively, of 72 serum samples collected from pigs experimentally
      infected with a 1992 SIV isolate (A/Swine/IA/40776/92). The presence of
      antibodies in these experimental samples was confirmed by HI tests in which all
      72 samples were positive against the homologous virus, a more recent H1N1 SIV
      isolate (A/Swine/NVSL/01) supplied by National Veterinary Services Laboratories,
      Ames, Iowa, and a 1999 H1N1 isolate currently used in a commercial vaccine. On
      testing 780 field samples, an overall agreement of 85.5% was generated between
      the HI and ELISA. This study demonstrated that the ELISA is a useful
      serodiagnostic screening test at herd level for detecting swine antibodies
      against SIV. However, a new SIV isolate representing current SIV strains
      circulating in the field is needed to replace the older isolates used in the HI
      and ELISA to increase the test accuracy for serodiagnosis of SIV.

PMID- 14974855
TI  - Keratinizing ameloblastoma in a 9-month-old llama (Lama glama).
AB  - A 9-month-old male llama (Lama glama) was presented because of a rapidly growing
      mass on the right side of the face. Radiographs revealed a marked expansion of
      the right caudal face region with bone lysis involving the maxilla and the nasal,
      lacrimal, zygomatic, and palatine bones. Cytologically, the mass consisted of
      atypical round to polygonal cells with round nuclei and basophilic cytoplasms
      that formed acini and rows. Histologically, the mass consisted of anastomosing
      cords and sheets of neoplastic odontogenic epithelial cells embedded in a loose
      fibrovascular connective tissue. Single layers of peripheral, polarized,
      palisading, columnar epithelial cells were seen at the edges of some cords.
      Within the centers of the cords, epithelial cells showed rapid progression to
      keratin production. The histologic diagnosis was keratinizing ameloblastoma.
      Ameloblastomas are neoplasms of odontogenic epithelium that tend to be locally
      aggressive and can cause substantial destruction of bony structures. Because
      ameloblastomas do not tend to metastasize, they can be successfully treated by
      complete surgical excision, performed before extensive bony destruction occurs.
      Ameloblastoma, although expected to be rare, should be onthe list of differential
      diagnoses for facial swelling in llamas.

PMID- 14974856
TI  - Infection control for the otolaryngologist in the era of severe acute respiratory
      syndrome.
AB  - OBJECTIVES: Severe acute respiratory syndrome (SARS) has affected more than 8400
      persons in 28 countries, with more than 800 deaths. The current SARS outbreak,
      especially in North American health care centers, has motivated a re-evaluation
      of infection control practices in the hospital and clinic environment. These
      considerations are particularly important to otolaryngology, in which examination
      and diagnostic procedures often bring the otolaryngologist in close--if not
      direct--contact with the patient's upper airway, mucosa, and secretions. The
      otolaryngologist is at increased risk of contracting a respiratory pathogen.
      METHOD: A joint effort by the Department of Otolaryngology at Queen's University
      and the Infection Control Services of the Hotel Dieu Hospital, Kingston, Ontario,
      was carried out to develop specific infection control guidelines for the
      otolaryngologists using strategies from the Centers for Disease Control and
      Prevention in the United States and the Laboratory Center for Disease Control,
      Health Canada. RESULTS: A set of specific recommendations was developed for the
      otolaryngologists to augment current infection control, including diligent use of
      personal protective equipment with every patient encounter. Moreover, this
      equipment should be removed according to specific protocol, to avoid
      contamination of self, others, and surroundings. Finally, a number of practice
      modifications are being adopted as prudent precautionary measures. CONCLUSION: It
      is essential to adhere to these recommendations in order to protect the health
      and safety of clinicians, colleagues, and patients.

PMID- 14974857
TI  - Intratympanic gentamicin for intractable Meniere's disease: 5-year follow-up.
AB  - OBJECTIVE: To determine the efficacy and morbidity of intratympanic gentamicin
      titration therapy on patients with incapacitating unilateral Meniere's disease.
      METHOD: The study consisted of a retrospective chart review and patient
      interviews. Sixty-eight patients had been followed for a minimum of 24 months and
      were reported on in an earlier study. Forty-six of these individuals were
      available for detailed follow-up at 5 years post-gentamicin therapy. MAIN OUTCOME
      MEASURES: Vertigo frequency, hearing status, personal disability ratings, and
      tinnitus level before and after gentamicin therapy were measured. RESULTS:
      Seventy-four percent of patients showed complete vertigo control and an
      additional 7% showed substantial vertigo control. There was also significant
      improvement in personal ratings of social and economic functioning. Overall, the
      group showed no combined statistically significant changes in any of the hearing
      parameters. CONCLUSION: Intratympanic gentamicin titration therapy provides
      excellent vertigo control, with a similarly significant improvement in both
      personal and occupational functioning.

PMID- 14974858
TI  - Assessment of the protective effects of amifostine against cisplatin-induced
      toxicity.
AB  - OBJECTIVE: The goals of this study were to determine whether the toxicity of
      cisplatin, a chemotherapeutic alkylating agent, could be reduced by the use of
      amifostine and to determine whether amifostine alone could cause ototoxicity.
      STUDY DESIGN: Prospective, animal study. METHODS: Auditory brainstem response
      click threshold, latencies, and blood work were used to measure ototoxicity,
      nephrotoxicity, and myelotoxicity before and 4 weeks after treatment. Groups of
      guinea pigs received either cisplatin alone (30 mg/kg), amifostine (1000 mg/kg),
      cisplatin plus amifostine (1000 mg/kg), or no agent. RESULTS: Amifostine reduced
      the hearing loss caused by cisplatin for many animals. Amifostine partially
      protected against cisplatin-induced ototoxicity and renal toxicity. We did not
      find evidence for myelotoxicity owing to cisplatin in this sample. CONCLUSION:
      Amifostine may have a role in reducing toxicity or permitting larger doses of
      cisplatin to be given, but toxicity can still be significant even with
      protection.

PMID- 14974859
TI  - Parotid surgery in an outpatient setting: the Vancouver Hospital experience.
AB  - OBJECTIVE: The goal of the present study was to review our experience with
      parotid surgery in an outpatient setting. Particular attention was given to
      examining the demographics of the population suitable for this approach as well
      as to evaluating complication and readmission rates. Waiting times for surgery
      were reviewed. Our experience is then compared with that of other researchers
      reported in the literature. METHODS: A retrospective chart review of 76 patients
      undergoing parotid surgery by a single surgeon in a free-standing surgical centre
      associated with Vancouver General Hospital, a tertiary teaching facility, was
      undertaken for the following: age, gender, American Association of Anesthesiology
      classification, time between initial visit and surgery, type of procedure,
      pathology, operative and recovery times and rates of complications, emergency
      department visitation, and readmission. RESULTS: Thirty-seven males and 39
      females with a mean age of 44.8 +/- 16.2 years were reviewed. Mean operative and
      recovery times were 109.8 +/- 20 and 268.6 +/- 58 minutes, respectively. The
      minor complication rate was 6.6%. One patient (1.3%) required readmission and two
      others (2.6%) visited the emergency department. CONCLUSIONS: Parotid surgery is
      possible on an outpatient basis, given appropriate patient selection. Our rates
      of complications, emergency department visitation, and hospital admission compare
      favourably with those reported in the literature.

PMID- 14974860
TI  - American Society of Anesthesiology classification may predict severe post
      tonsillectomy haemorrhage in children.
AB  - OBJECTIVE: The purpose of this study was to identify pre- or intraoperative
      markers for post-tonsillectomy haemorrhage (PTH) that may help to define in
      /outpatient tonsillectomy. DESIGN: A retrospective case-control study of
      tonsillectomized patients. SETTING: A tertiary referral university hospital.
      METHODS: Twenty-three children with PTH were compared with 69 tonsillectomized
      age- and sex-matched children without bleeding. The cohort consisted of 559
      individuals under 18 years old who were scheduled for tonsillectomy or
      adenotonsillectomy between 1996 and 2000. MAIN OUTCOME MEASURES: Physical and
      analytical variables were investigated, including blood pressure, haemoglobin and
      haematocrit levels, coagulation profile, American Society of Anesthesiology (ASA)
      physical status classification, indications for surgery, obstructive sleep apnea
      and snoring, surgical experience, addition of adenoidectomy, method of
      tonsillectomy, type of anaesthesia, method of haemostasis, and total surgical
      time. Statistical significance was calculated by the Mann-Whitney U test and
      Fisher's exact test. RESULTS: The incidence of PTH was 4.11%, and all but one
      case were primary bleedings. Nineteen cases occurred within the first 8 hours. A
      possible risk marker identified was ASA class 2 (odds ratio = 5.69, p = .04).
      Other investigated factors were not significant. CONCLUSIONS: The ASA
      classification may be a predictor for PTH and could be used to select outpatients
      before tonsillectomy.

PMID- 14974861
TI  - Sudden sensorineural hearing loss: literature survey on recent studies.
AB  - Sudden sensorineural hearing loss (SSHL) is a symptom of cochlear injury. It is
      characterized by sudden onset, and, within a few hours, it reaches its maximum
      peak. It may be accompanied by vertigo and tinnitus. Many hypotheses have been
      advanced to explain its etiology: viral inflammation, vascular diseases, allergic
      reaction, rupture of intralabyrinthine membranes, and autoimmune diseases. The
      decrease in hearing may be unilateral or bilateral. To assess the histopathology
      of the labyrinth in cases of SSHL and to provide a better understanding of the
      etiopathogenesis, many studies have been carried out. Atrophy of the organ of
      Corti, loss of cochlear neurons, labyrinthine fibrosis, formation of new bone,
      and degeneration of the spiral ligament, vascular stria, hairy cells, dendrites,
      and apical spiral ganglion cells have been reported in temporal bone studies. In
      this article, new studies on the histopathologic and therapeutic bases of SSHL
      are reviewed.

PMID- 14974862
TI  - Anatomic landmarks for locating parotid lesions in relation to the facial nerve:
      cross-sectional radiologic study.
AB  - OBJECTIVES: To determine the accuracy of using surrogate anatomic structures
      radiologically to predict the relation of parotid lesions to the intraparotid
      facial nerve. SETTING: Tertiary centre. DESIGN: Retrospective. PATIENTS AND
      METHODS: All patients with parotid masses over a 5-year period who undertook
      parotidectomy were considered. A radiologist and an otolaryngologist reviewed the
      images. Their decision regarding the location of the lesions using four surrogate
      structures was compared with intraoperative documentation. OUTCOME MEASURE: We
      determined the sensitivity and the specificity of using the external carotid
      artery, retromandibular vein, posterior belly of the digastric muscle, and tragal
      pointer. RESULTS: Thirty films were examined (24 magnetic resonance images [MRIs]
      and 6 computed tomographic [CT] scans). The sensitivity and the specificity of
      the retromandibular vein were 0.85 and 0.57, respectively, whereas for the
      external carotid artery, they were 0.94 and 0.3, respectively. It was too
      impractical to relate the other two structures to the lesions. CONCLUSIONS: The
      retromandibular vein is the most accurate surrogate structure to use on MRI or CT
      for predicting the location of a parotid lesion to the facial nerve. However, the
      substantial proportion of deep lesions misjudged limits the benefit of performing
      the imaging.

PMID- 14974863
TI  - Cytokeratin subtypes in thyroid tumours: immunohistochemical study with emphasis
      on the follicular variant of papillary carcinoma.
AB  - OBJECTIVE: The follicular variant of papillary thyroid carcinoma (FV-PTC) may be
      difficult to differentiate from other thyroid neoplasms with follicular
      architecture such as follicular adenoma, follicular carcinoma, and dominant
      nodules in nodular goitre. Obvious differences in treatment and expected outcome
      between these lesions mandate that the distinction between them be made
      accurately. To decrease the subjectivity of this differential diagnosis, we
      undertook this study to determine if any difference in cytokeratin profile exists
      between FV-PTC and other follicular lesions of the thyroid gland. DESIGN:
      Immunohistochemical analysis based on a retrospective pathology review. SETTING:
      Vancouver General Hospital, Vancouver, BC. METHODS: The files of the Vancouver
      General Hospital anatomic pathology laboratory were searched for cases of typical
      papillary thyroid carcinoma (PTC), FV-PTC, follicular adenoma, follicular
      carcinoma, and nodular goitre. The slides and reports were reviewed, and those
      cases with confirmed diagnosis and adequate tissue were selected for inclusion in
      the study. Monoclonal antibodies to cytokeratin 19 (CK19), 20 (CK20), and 7 (CK7)
      were applied to formalin-fixed, paraffin-embedded tissue sections. RESULTS: All
      cases of PTC, including FV-PTC, as well as all follicular adenomas, follicular
      carcinomas, and nodular goitres, stained positively for CK7 and, except for a
      single follicular carcinoma, were negative for CK20. CK19 decorated almost all
      PTCs, including FV-PTC, although the staining was sometimes focal. The majority
      of the cases of follicular adenoma, follicular carcinoma, and nodular goitre were
      negative or showed focal staining with CK19, although occasional cases showed
      diffuse positivity. CONCLUSIONS: CK19 strongly stains the majority of PTC,
      including FV-PTC, in a diffuse manner. However, overlap with the staining seen in
      other follicular lesions limits its utility in a routine diagnostic setting.

PMID- 14974864
TI  - Quality of life following ear surgery measured by the 36-item Short Form Health
      Survey and the Glasgow Benefit Inventory.
AB  - BACKGROUND: Quality of life (QOL) following ear surgery is an important outcome
      measure. Most QOL studies are retrospective and therefore biased by uncertainties
      about preoperative QOL. OBJECTIVES: The primary objective was to prospectively
      assess change in QOL following ear surgery. The secondary objective was to
      determine if QOL was associated with audiometric change. METHODS: Twenty-six
      patients undergoing ear surgery were studied prospectively between 1999 and 2000.
      Before and after surgery, patients received a detailed audiometric evaluation and
      completed a generic (36-Item Short Form Health Survey [SF-36]) and a disease
      specific (Glasgow Benefit Inventory [GBI]) QOL instrument. RESULTS: Significant
      audiometric improvement was noted following surgery. For six of the eight
      subsections of the SF-36, there was significant improvement following surgery.
      Three subsections correlated with the reduction in air-bone gap. GBI scores
      indicated that 50% of patients experienced an increase in QOL. The GBI correlated
      with one subsection of the SF-36. Higher GBI scores were associated with a
      reduction in the air-bone gap, but there was no significant correlation.
      CONCLUSIONS: QOL improved following ear surgery. QOL can be effectively assessed
      using both generic and disease-specific instruments. Improvement in the SF-36
      score was correlated with reduction of the air-bone gap, suggesting that improved
      hearing was a determinant of improved QOL.

PMID- 14974865
TI  - HER2/neu and Ki-67 as prognostic indicators in mucoepidermoid carcinoma of
      salivary glands.
AB  - INTRODUCTION: Mucoepidermoid carcinoma is the most common salivary gland
      malignancy, representing up to 30% of all cases. Despite attempts to correlate
      histopathologic grades to clinical outcomes, some histologically "low"-grade
      lesions continue to behave aggressively despite appropriate treatment. OBJECTIVE:
      This preliminary study will attempt to evaluate the use of immunohistochemical
      markers HER2/neu and Ki-67 as prognostic markers of biologic aggressiveness for
      mucoepidermoid carcinoma of the salivary glands. DESIGN AND METHODS: A
      retrospective chart review of 42 patients with mucoepidermoid carcinoma of major
      and minor salivary glands treated between 1970 and 1995 was conducted. A
      combination of primary resection with or without postoperative irradiation was
      used. Histologic grading and correlation with outcome analyses are provided.
      RESULTS: In the current study, positive HER2/neu staining and strong Ki-67
      staining occurred in patients with high-grade mucoepidermoid carcinoma, whereas
      low-grade carcinoma was correlated with negative or weak staining. CONCLUSION:
      These preliminary results indicate that, overall, the overexpression of both the
      HER2/neu and the Ki-67 oncoproteins may serve as prognostic markers for poor
      outcome in salivary gland mucoepidermoid carcinoma.

PMID- 14974866
TI  - Cartilaginous tumours of the larynx.
AB  - Cartilaginous tumours of the larynx are rare. Chondrosarcomas represent the most
      common sarcoma involving this site. A series of seven patients with the diagnosis
      of chondrosarcoma of the larynx from the cancer registry at the University of
      Michigan Medical Center from 1975 to 1997 and one recent case from the Ann Arbor
      Department of Veterans Affairs Hospital were identified. One patient with a
      laryngeal chondroma was also included in the series. Pertinent clinical,
      pathologic, and therapeutic data were reviewed. In three of the nine patients,
      tumours involved the thyroid cartilage; the remainder, including the chondroma,
      arose from the cricoid cartilage. Four of the chondrosarcomas were
      histopathologic grade I, three were grade II, and one was grade III. Surgical
      treatment of the chondrosarcomas included five total laryngectomies, three
      laryngofissures with resection, and a partial cricoid resection. Six patients are
      alive without disease, including one patient who had direct spread to the thyroid
      gland and a peristomal recurrence that was excised. The patient with a grade III
      tumour developed pulmonary metastases 6 months after total laryngectomy and
      radiation therapy and died. One patient died of other causes. These findings
      confirm previous reports that chondrosarcomas are usually slow growing and
      demonstrate an indolent clinical course and that low-grade chondrosarcomas
      arising in the larynx may be excised with close surgical margins without
      compromising survival. This series suggests that local recurrence of low-grade
      lesions can be salvaged surgically, even after total laryngectomy, and that high
      grade chondrosarcomas, although exceedingly rare, are much more aggressive
      neoplasms with a greater tendency to metastasize.

PMID- 14974867
TI  - Epidural abscess drainage using endoscopic sinus surgery: a first case in the
      literature.

PMID- 14974868
TI  - Successful management of persistent hyperparathyroidism without finding the
      adenoma.

PMID- 14974869
TI  - Dental implant migration into the ethmoid sinus.

PMID- 14974870
TI  - Squamous cell carcinoma of the lip in long-standing oral lichen planus: case
      report, surgical approach.

PMID- 14974871
TI  - Primary hydatid cyst: a rare cause of neck mass.

PMID- 14974873
TI  - A review of self-report instruments measuring health-related work productivity: a
      patient-reported outcomes perspective.
AB  - Health impairment often leads to work impairment in the form of both absenteeism
      and presenteeism (i.e. reduced productivity while at work). Several self-report
      productivity instruments have been designed over the past few years to measure
      the impact of illness on productivity at work and/or in non-work activities. In a
      review of the literature we identified six generic subjective instruments - the
      Endicott Work Productivity Scale, Health and Labor Questionnaire, Health and Work
      Questionnaire, Health and Work Performance Questionnaire, Work Limitations
      Questionnaire (WLQ) and the Work Productivity and Activity Impairment
      Questionnaire (WPAI) - that could theoretically be used in any working
      population. These instruments were usually validated against other subjective
      measures (such as health-related QOL). Each productivity instrument has benefits
      in certain research settings, but the psychometric properties of the WPAI have
      been assessed most extensively. It was the most frequently used instrument and
      has also been modified to measure productivity reductions associated with
      specific diseases (e.g. allergic rhinitis, gastro-oesophageal reflux disease,
      chronic hand dermatitis). The WLQ has also been tested extensively to measure the
      general health impact and impact of specific conditions. Two migraine-specific
      subjective instruments were also identified: the Migraine Disability Assessment
      questionnaire and the Migraine Work and Productivity Loss Questionnaire, of which
      the latter was found to have better psychometric properties. Productivity
      outcomes are useful in that they characterise the impact of an illness in the
      workplace and show the effect of treatment on productivity. Evidence of
      psychometric properties and generalisability of different instruments was found
      to a varying degree. Thus, further research is needed to assess the accuracy and
      usefulness of individual instruments in certain research settings. Health-related
      productivity has been increasingly recognised as an important component of the
      burden of illness associated with a given disease; without it, one cannot
      reliably assess this burden.

PMID- 14974872
TI  - Aggressive non-Hodgkin's lymphoma: economics of high-dose therapy.
AB  - High-intermediate grade non-Hodgkin's lymphoma (NHL) is an aggressive form of the
      disease, which can respond well to combination chemotherapy, with long-term
      survival seen in 40-50% of patients. When NHL relapses following standard
      treatment, high-dose chemotherapy with peripheral blood stem cell or bone marrow
      support may still cure a significant proportion of patients. Despite a
      significant rise in the incidence of NHL over recent years, there remains only
      limited published economic study concerning the overall lifetime cost of
      treatment, the cost effectiveness of specific treatments or the overall societal
      cost burden of the disease. The majority of studies identified for the purposes
      of this review considered the cost of alternative forms of chemotherapy and bone
      marrow support strategies for patients with advanced disease. Data from these
      studies suggest that there is a definite trend towards reduced costs for high
      dose therapy, possibly reflecting increasing technical experience and improved
      bone marrow recovery through the use of stem cell transplantation and growth
      factors. The limited number of cost-effectiveness evaluations suggest that high
      dose therapy, following a chemosensitive relapse, is likely to be considered
      favourable against commonly quoted cost-effectiveness thresholds. Cost
      effectiveness is becoming an increasingly important factor to consider in the
      formal assessment of new interventions conducted by groups such as the UK
      National Institute for Clinical Excellence. In light of the increasing incidence
      of NHL and the extended use of high-dose treatments in other subgroups of
      patients, there is a need for increased research into the economics of new
      interventions for NHL.

PMID- 14974874
TI  - Development and validation of an acceptability and satisfaction questionnaire for
      a contraceptive vaginal ring, NuvaRing.
AB  - OBJECTIVE: To validate an acceptability questionnaire for NuvaRing, a new
      combined contraceptive vaginal ring. METHODS: A 21-item questionnaire was
      developed covering: ease of ring use, ease of package use, clarity of
      instructions, sexual comfort, cycle-related characteristics, compliance and
      satisfaction. A total of 2145 women completed the questionnaire after 3, 6 or 13
      cycles of NuvaRing use. The psychometric properties and predictive value of the
      questionnaire were assessed using cycle 3 data (n = 1950). The quality of
      completed questionnaires, item content analysis, construct validity, internal
      consistency reliability, known groups validity and predictive validity were
      evaluated. RESULTS: Excluding non-ordinal items, 0.6% of the data were missing.
      Principal component analysis of 15 ordinal items indicated that two hypothesised
      dimensions ('ease of package use' and 'clarity of instructions') were
      consistently linked and so were combined into a single 'ease of comprehension'
      scale. Item convergent validity (the degree of correlation between an item and
      its own scale) was 100% for 'ease of ring use' (r = 0.44) and 'satisfaction' (r =
      0.58), 83% for 'ease of comprehension' (r = 0.25-0.62) and 67% (r = 0.38-0.54)
      for 'sexual comfort', but 0% for 'cycle-related characteristics' (r = 0.31). Item
      discriminant validity (the degree to which an item correlates with its own scale
      compared with other scales) was >/=96% for all dimensions. Internal consistency
      reliability was acceptable for all dimensions (adjusted Cronbach's alpha
      coefficient >0.70). Satisfaction was higher than in the complementary groups for
      respondents who had no adverse events, chose NuvaRing as the best method of
      contraception or completed the study; this indicated good known groups validity.
      Low satisfaction with the method was a good predictor of early discontinuation
      after cycle 3, indicating that the questionnaire had good predictive validity.
      CONCLUSIONS: The acceptability questionnaire has good psychometric properties and
      can predict early discontinuation of the NuvaRing vaginal ring method of
      contraception.

PMID- 14974875
TI  - Cost effectiveness of peginterferon alpha-2a plus ribavirin versus interferon
      alpha-2b plus ribavirin as initial therapy for treatment-naive chronic hepatitis
      C.
AB  - INTRODUCTION: In adults with previously untreated chronic hepatitis C (CHC), the
      combination of peginterferon alpha-2a plus ribavirin produces a higher rate of
      sustained virological response (SVR) than interferon alpha-2b plus ribavirin, but
      it is still unproven whether this increase is cost effective. The objective of
      this study was to determine if the gain in SVR with peginterferon alpha-2a plus
      ribavirin is worth the incremental cost. METHODS: We constructed a Markov model
      of disease progression in which cohorts of patients received peginterferon alpha
      2a plus ribavirin or interferon alpha-2b plus ribavirin for 48 weeks (hepatitis C
      virus [HCV] genotype 1 and non-1 patients with fibrosis) or 24 weeks (genotype
      non-1 patients without fibrosis), and were followed for their expected lifetimes.
      The reference patient was a 45-year-old male with CHC without cirrhosis. The SVRs
      with peginterferon alpha-2a plus ribavirin and interferon alpha-2b plus ribavirin
      used to populate the model were 46% and 36% for patients infected with HCV
      genotype 1 and 76% and 61% for patients infected with HCV non-1 genotypes,
      respectively. QOL and costs for each health state were based on literature
      estimates and on Italian treatment patterns. Costs were in 2002 euros and
      benefits were discounted at 3%. Sensitivity analyses on key clinical and economic
      parameters were performed. The analysis was reported from the perspective of the
      Italian National Health Service. RESULTS: In patients infected with HCV genotype
      1, peginterferon alpha-2a plus ribavirin increased life-years (LYs) by 0.78 years
      and QALYs by 0.67 years, compared with interferon alpha-2b and ribavirin. The
      incremental cost per LY and QALY gained was euro9433 and euro10 894,
      respectively. In patients infected with HCV non-1 genotypes, peginterferon alpha
      2a plus ribavirin increased LYs by 1.17 and QALY by 1.01 years, compared with
      interferon alpha-2b plus ribavirin. The incremental cost per LY and QALY gained
      was euro3261 and euro3766, respectively. Using genotype distribution estimates,
      the weighted average ICER for all genotypes was euro6811 per LY gained and
      euro7865 per QALY gained. CONCLUSION: Our model suggests that peginterferon alpha
      2a plus ribavirin is cost effective compared with conventional interferon alpha
      2b plus ribavirin for treatment of naive adults with CHC, regardless of HCV
      genotype, under a wide range of assumptions regarding treatment effectiveness and
      costs.

PMID- 14974876
TI  - The NICE reference case requirement: implications for drug manufacturers and
      health systems.

PMID- 14974877
TI  - The NICE reference case requirement: more pain for what, if any, gain?

PMID- 14974878
TI  - [Changes in the surroundings].

PMID- 14974879
TI  - [Cost-minimization study on the prescription of intravenous proton pump
      inhibitors: pantoprazole versus omeprazole].
AB  - OBJECTIVE: To compare and quantify intravenous omeprazole versus intravenous
      pantoprazole prescription habits in common acid-related diseases such as gastro
      esophageal reflux disease, duodenal ulcer, and gastric ulcer. MATERIAL AND
      METHODS: We designed an observational, longitudinal prospective and multicenter
      cost-minimization study to be carried out in Spanish hospitals. RESULTS: The
      pantoprazole regimen consisted of 40 mg/day (median), one half of that of
      omeprazole with 80 mg/day overall for these conditions (p < 0.05). This dosage
      was significantly different for duodenal ulcer (40.0 +/- 0.0 versus 90.6 +/- 22.5
      mg/day, p < 0.05), and gastric ulcer (50.3 +/- 17.8 versus 85.8 +/- 39 mg/day, p
      < 0.05), but not for gastro-esophageal reflux disease (50.9 +/- 18.7 versus 62.2
      +/- 21.1, p > 0.05). Costs for these regimens make treatments using pantoprazole
      54% less expensive than treatments using omeprazole. By indication, the cost of
      duodenal ulcer treatment was 65% less expensive, and that of gastric ulcer 53%
      less expensive. CONCLUSIONS: Cost differences amount to approximately one half in
      treatments using pantoprazole, which is primarily due to the use of doses higher
      than indicated in treatments using intravenous omeprazole. To reduce expenses
      stemming from the inadequate use of intravenous proton pump inhibitors the use of
      pantoprazole is brought forward as a valid option.

PMID- 14974880
TI  - [Profhylaxis and treatment of hereditary and acquired angioedema at HUB; use of
      the C1-esterase inhibitor].
AB  - INTRODUCTION: Hereditary and acquired angioedema result from a deficiency in
      first complement component esterase (C1-esterase) inhibitor. It is characterized
      by transient subcutaneous tissue, intestinal wall, and upper airway swelling,
      which may lead to asphyxia and death. The pathophysiology, classification,
      diagnosis, and treatment of this condition are discussed, as is the follow-up of
      patients diagnosed with angioedema who received 1 vial of concentrated C1-INH
      (Berinert); the contribution of the Pharmacy Department in the dispensation and
      control of said drug is also assessed. MATERIAL AND METHODS: PubMed and other
      relevant sources were searched. Patient, dispensation, and Berinert(R) indication
      data were collected from controlled prescriptions; follow-up was completed by
      performing a medical history, collecting laboratory data, and patient interview
      when needed. RESULTS: Eight out of 9 cases were of hereditary angioedema, and 1
      case was of acquired angioedema. Danazol was used as long-term prophylaxis in 8
      patients, but side effects forced discontinuation in some of them. The C1-INH
      concentrate was effective in 6 acute episodes that were detected during the
      study, as well as in 3 surgical prophylaxis cases (overall use 6,500 U).
      CONCLUSION: Danazol was effective as prophylactic treatment, but had severe side
      effects. The C1-INH concentrate was effective both as prophylactic therapy and
      treatment for acute episodes. An adequate stock of this product will be available
      at the Pharmacy Department.

PMID- 14974881
TI  - [Drug information made available to the population via Internet from a Pharmacy
      Department].
AB  - OBJECTIVES: To describe and discuss the work of a Pharmacy Department for the
      health-care portal www.viatusalud.com. METHODS: Using a web portal, a Pharmacy
      Department develops and updates a vademecum on drugs, and answers enquiries by
      end-users. RESULTS: On December 31, 2002 more than 750 records on drugs were
      available, and 3030 enquiries had been answered. CONCLUSIONS: With this drug
      information and online enquiry service, our Pharmacy Department helps meet the
      demand of health-care information posed by the community and by patients
      previously seen at Clinica Universitaria. In addition, it allows areas of
      improvement to be detected in the information to be offered to patients fron a
      Pharmacy Department, and represents a tertiary source of information for health
      care professionals.

PMID- 14974882
TI  - [New perspectives in the treatment of rheumatoid arthritis].
AB  - Rheumatoid arthritis affects 0.5% of the Spanish population. It is a disabling,
      slowly progressive disease which primarily affects joints, and results in
      functional impairment and important quality of life reductions in most patients.
      Its etiology is presently unknown. Treatment is aimed at reducing inflammatory
      activity, preserving function, and delaying joint lesions, which result in high
      morbidity and mortality. Treatment is usually initiated with NSAIDs and
      glycocorticoids to relieve symptoms, and then followed by disease-modifying anti
      rheumatic drugs. Recent advances in the understanding of etiopathogenic
      mechanisms have permitted the development of novel, much more specific treatments
      aimed at modifying disease progression. These include those acting on the tumoral
      necrosis factor (TNF) - etanercept and infliximab - and more recently an
      interleukin-1 receptor antagonist - anakinra. Despite their demonstrated improved
      tolerance and faster onset of action, their high cost warrants further efficacy
      studies and the establishment of objective criteria for their use.

PMID- 14974883
TI  - [Chronic hepatitis C drug therapy update].
AB  - Chronic hepatitis produced by Hepatitis C Virus (HCV) is a major health problem
      with relevant healthcare and financial consequences. The major goal of chronic
      hepatitis C treatment is the eradication of HCV, which is considered an
      equivalent of disease cure and is defined in terms of sustained viral response
      (SVR). Therapeutic expectancy has greatly improved over the past five years,
      going from efficacy rates of approximately 15% SVR using standard interferon
      monotherapy to an overall response of 55% using pegylated interferons in
      association with ribavirin. In addition, significant differences in efficacy have
      been found specially for patient stratification by genotyping and viral load.
      Such satisfactory clinical findings are associated with a most relevant increase
      in pharmaceutical costs, as they entail therapeutic measures of high financial
      impact. Therefore, their inclusion within a Hospital"s Pharmacotherapeutic Guide
      must be regarded as a part of a rational drug use policy, and usage criteria
      should be established and compiled into a therapeutic protocol including
      prescriptions and pharmacotherapeutic monitoring.

PMID- 14974884
TI  - [Phenytoin: paradoxical toxicity; a discussion of 4 cases].
AB  - INTRODUCTION: Phenytoin overdosing results in a wide variety of signs and
      symptoms - ataxia, nistagmus, loss of consciousness. On occasions increased
      frequence of seizures may be seen in patients with high phenytoin serum levels
      and no evidence of standard toxicity symptoms - paradoxical toxicity. OBJECTIVE:
      To study the frequency of phenytoin paradoxical toxicity, and to analyze
      patients" clinical status. PATIENTS AND METHOD: Prospective study of 100% of
      patients monitored by the Pharmacy Department during August-December, 1998 and
      who had phenytoin serum levels above therapeutic range and seizures. Laboratory
      determinations in samples was performed by polarized immunofluorescence analysis.
      The outcome of each patient was monitored through their pharmacotherapeutic
      record and clinical history. RESULTS: The number of patients was 1706; 124 of
      wich had serum levels above the therapeutic range. Out of this group, 3 males and
      1 female, with ages ranging from 17 to 73, a diagnosis of epilepsy, and chronic
      therapy using phenytoin, come to our Emergency Department because of convulsions.
      Serum levels of phenytoin were ordered due to suspected lack of compliance or
      underdosing. In all 4 patients phenytoin was discontinued until the therapeutic
      range was reached, to be then reset with plasma level-adjusted dosages.
      CONCLUSIONS: Paradoxical toxicity may lead to errors, and therefore we should
      rule out such possibility in patients with exacerbated epilepsy undergoing
      treatment with phenytoin.

PMID- 14974885
TI  - [Protein C concentrate in the treatment of severe sepsis in the pediatric
      setting].
AB  - Patients with severe sepsis develop acquired protein C deficiency, and the extent
      of such deficiency and negative clinical outcomes correlate. Replacing this
      protein may help prevent such a condition. Two protein C types are commercially
      available - concentrated and activated proteins. None is registered for the
      treatment of severe sepsis in the pediatric setting. Experience with protein C in
      this group of conditions is limited. Appropriate clinical trials are required to
      establish effectiveness and safety, and to elucidate the role of either protein C
      type in the management of this condition in the pediatric setting. This paper
      discusses experience with the use of protein C concentrate as an adjuvant
      treatment in addition to conventional therapy in three children with severe
      sepsis at a Pediatric Intensive Care Unit. In all 3 cases of our study, high
      levels of protein C correlated to coagulation parameter normalization and reduced
      dimer D levels. Two out of three had a favorable outcome following treatment,
      whereas the third patient died as a result of septic shock and multiple organ
      dysfunction.

PMID- 14974886
TI  - [Drug safety. Preventing medication errors].

PMID- 14974887
TI  - [International therapeutics].

PMID- 14974888
TI  - [Continuous domiciliary oxygen therapy: a right treatment if it is well done].

PMID- 14974889
TI  - [Value of pulse oxymetry for the follow-up control of domiciliary oxygen
      therapy].
AB  - OBJECTIVE: To evaluate long-term domiciliary oxygen therapy (LTOT) in our setting
      and the utility of pulse oxymetry for follow-up control. PATIENTS AND METHOD: 140
      patients were studied. The data on the indication for LTOT and the degree of
      therapeutic compliance were obtained by means of a clinical interview;
      spirometry, full blood count, arterial blood gas measurement, and pulse oxymetry
      were also carried out. RESULTS: 12 (8.6%) patients who fulfilled criteria for
      provisional oxygen therapy were excluded and 22 (15.7%) due to recent
      exacerbations. Of the remaining 106 individuals, 67 (63%) were men and 39 (37%)
      women, and the mean age was 73 +/- 12 years. 54% (57/106) of the patients used
      the oxygen therapy for at least 15 hours/day. Only 36 (34%) patients fulfilled
      the indication criteria for LTOT and only 24 (23%) both fulfilled the indication
      criteria and demonstrated appropriate administration of the LTOT. The oxygen
      saturation measured by pulse oxymetry (SpO2) showed a good correlation with the
      partial pressure of oxygen (PaO2) obtained by arterial blood gas measurement
      (r=0.857 and K=0.937). CONCLUSIONS: In our setting, the follow-up control of LTOT
      and therapeutic compliance were not optimal. The SpO2 shows a good correlation
      with the PaO2 and represents a good alternative for the follow-up control of
      LTOT.

PMID- 14974890
TI  - [Epidemiologic survey of acute poisoning in the south area of the community of
      Madrid. The VEIA 2000 Study].
AB  - OBJECTIVE: Extensive observational studies of acute intoxications (AI) allow the
      detection of trend changes indispensable for the design of preventive actions.
      VEIA is an evolutional study of AI attended at the Emergency Services of the
      Hospital "Doce de Octubre" of Madrid over all-round annual periods (1979, 1985,
      1990, 1994 and 1997); we present the results of 2000 and compare them with those
      of previous years. METHODS AND RESULTS: An identical method was used. The
      hospital attended 1,128 AI, 88% of them voluntary. There were 451 suicide
      attempts. Forty four per cent of drugs involved were benzodiazepines. Alcohol
      represented 75% of non-pharmacological toxic substances and drugs, 19%.
      CONCLUSIONS: An increase of AI caused by alcohol and drugs was observed among
      women, as well as a decrease of suicide attempts, which reflects an approximation
      of man/woman roles. An aging trend was observed in suicide attempts (Is suicide
      "outmoded" among young people?), along with two patterns: Suicide attempts with
      drugs had a mortality rate of 0.1% and suicide attempts without drugs, of 3%. Two
      out of five men attempting suicide had drug addictions. There had been a
      reduction of benzodiazepines use and substitution of aspirin for paracetamol and
      of other analgesics for NSAID. Alcohol was the predominant non-pharmacological
      toxic substance, but had decreased 11%. Drugs, that had surpassed the traditional
      poisons (gases, solvents, etc.) represented 40% more than in 1997. When 1994 and
      2000 were compared, heroine had not changed significantly, but cocaine had
      increased from 13 cases to 67 and amphetamines type MDMA had increased
      geometrically.

PMID- 14974891
TI  - [Preliminary study of the drug consumption in hospitalized elders].
AB  - BACKGROUND: The absence of studies that evaluate the effect of the medical acts
      is an example of "mala praxis". The irrational use of medications is one of these
      cases. This study shows the characteristics of the drugs consumption in elders.
      MATERIAL AND METHODS: We include 53 elders hospitalized between 1/02/02 and the
      31/05/02. RESULTS: The elders received an average of 6.45 medicaments/day. The
      factors of more consumption are the origin from nursing home residents and the
      number of previous surgeries. The adverse effects were related in 25% of the
      hospitalizations. CONCLUSIONS: The basis of this situation is in the loss of the
      global perspective of the patients and in the abuse of the sanitary resources.
      Each drug is the result of an isolated medical act, determining the appearance of
      iatrogenic disease.

PMID- 14974892
TI  - [Study of the derivations to an external consultation of Internal Medicine: can
      be managed the waiting list?].
AB  - BACKGROUND: The lack of coordination and organization between primary and
      specialized attention, generates inefficiency bags in the area of external
      consultations. MATERIAL AND METHOD: The characteristics of the attention of 120
      patients derived consecutively to an external Internal Medicine consultation of a
      local hospital are analyzed. RESULTS: Of the 120 mentioned patients 19 did not
      appear (16.23%). 70.3% of the taken care of patients came from primary attention
      and 29.7% did it of specialized attention. Of the patients derived by primary
      attention: 63.3% went without data adapted in the derivation leaf, 59.2% did not
      contribute complementary diagnostic tests and 40.8% were registered in the first
      consultation. Of the patients derived from specialized attention: 100% contribute
      clinical information to the consultation, 90% contribute complementary studies
      and 56.65% are registered in the first consultation. CONCLUSIONS: The
      discontinuity in the attention between primary and specialized attention
      generates an inefficient use of the resources, that in the area of external
      consultations influences in the appearance of waiting lists.

PMID- 14974893
TI  - [Listeriosis in the adult. Revision of 10 cases].
AB  - Listeria monocytogenes is still a very rare opportunist infection in
      immunosuppressive patients. The clinical-epidemiological and therapeutic
      characteristics in 10 patients with infection produced by LM are reported--four
      of them had primary bacteriemia, three patients had a meningeal involvement,
      there were two patients with spontaneous bacterial peritonitis and one suffered
      from abdominal access. All of the patients had underlying disorders favouring the
      infection. Sepsis and meningeal syndrome were the most common presenting forms.
      Ampicillin was the most used antibiotic. The overall mortality was 40%.

PMID- 14974894
TI  - [Henoch-Schonlein purpura in adults: a study of 9 cases].
AB  - OBJECTIVE: Schonlein-Henoch purpura (PSH) is a predominantly pediatric vasculitis
      with, generally, a benign prognosis. However, in adults can acquire greater
      severity and more frequency of renal involvement. We report our experience with 9
      cases of this entity. MATERIAL AND METHODS: Retrospective review of the
      leukocytoclastic vasculitis admitted to our hospital in 1995-2002. Patients
      fulfilling > or =3 of Michels's criteria for PSH: a) palpable purpura; b)
      abdominal angina; c) gastrointestinal bleeding; d) hematuria; e) age >20 years;
      and f) absence of responsible medication), were identified. The incidence was
      0.65 cases/100,000 inhabitants >15 years, without seasonal predominance. We
      identified 9 patients (7 males, age range: 22 to 88 years). There was palpable
      purpura in 100%, gastrointestinal involvement in 67%, renal in 78%, and
      oligoarticular in 22%. Recovery was uneventful, except for a case with previous
      renal insufficiency. CONCLUSIONS: We found a low frequency of articular
      involvement and high renal affectation but with an excellent prognosis.

PMID- 14974895
TI  - [Gastric uptake of gallium67 in the human immunodeficiency virus infection].
AB  - Nowadays, the human immunodeficiency virus infection (HIV) is a chronic disease.
      In the frequent clinical situations with fever, lymph nodes and loss weight it is
      necessary to determine their etiology, for establishing a specific treatment.
      Gastrointestinal opportunistic infections or gastric lymphomatous or sarcomatous
      process, which can accumulate Ga67, may be present in the patient with acquired
      immunodeficiency syndrome. We report 2 cases with gastric uptake in which
      endoscopy and biopsy was obtained. In the first one, with previous treatment with
      omeprazol and almalgate for gastroesophagic reflux, endoscopy and biopsy were
      normal and in the second patient an Helicobacter pylori infection was diagnosed.
      We think that gastric uptake of Ga67 in HIV patients, must indicate to the
      clinician to rule out associated pathologies.

PMID- 14974896
TI  - [Hereditary angioedema of delayed onset].
AB  - Hereditary angioedema is a disorder characterized by episodes of angioedema of
      the skin, respiratory and gastrointestinal tract resulting from a defect in the
      C1 esterase inhibitor. The disease is hereditary. Inheritance is autosomal
      dominant with incomplete penetration. We report a 56-year-old man with edema in
      different locations as forearm, testicles and palms. It started recently. The
      study showed low levels of C4, and C1 inhibitor. He was diagnosed of hereditary
      angioedema and it was necessary the family study.

PMID- 14974897
TI  - [Osteoporotic hip fracture. Predictive factors of short-and long-term functional
      recovery].

PMID- 14974898
TI  - [Infective endocarditis of pacemakers leads].

PMID- 14974899
TI  - [Cardiogenic shock due to intestinal obstruction].

PMID- 14974900
TI  - [Spontaneous enterocutaneous fistula as sole manifestation of recidive in Crohn's
      disease].

PMID- 14974901
TI  - [Deep venous thrombosis associated with varicella pneumonia and anticardiolipin
      antibody].

PMID- 14974902
TI  - [Acute ischemia secondary to ergotism].

PMID- 14974903
TI  - [Xanthogranulomatous pyelonephritis mimicking colonic cancer].

PMID- 14974905
TI  - Editorial.

PMID- 14974904
TI  - [Opportunistic Campylobacter fetus bacteremia in an apparently healthy patient].

PMID- 14974906
TI  - Growth hormone, acromegaly, and heart failure: an intricate triangulation.
AB  - Short-term GH or IGF-I excess provides a model of physiological cardiac growth
      associated with functional advantage. The physiological nature of cardiac growth
      is accounted for by the following: (i) the increment in cardiomyocyte size occurs
      prevalently at expense of the short axis. This is the basis for the concentric
      pattern of left ventricular (LV) hypertrophy, with consequent fall in LV wall
      stress and functional improvement; (ii) cardiomyocyte growth is associated with
      improved contractility and relaxation, and a favourable energetic setting; (iii)
      the capillary density of the myocardial tissue is not affected; (iv) there is a
      balanced growth of cardiomyocytes and nonmyocyte elements, which accounts for the
      lack of interstitial fibrosis; (v) myocardial energetics and mechanics are not
      perturbed; and (vi) the growth response is not associated with the gene re
      programming that characterizes pathologic cardiac hypertrophy and heart failure.
      Overall, the mechanisms activated by GH or IGF-I appear to be entirely different
      from those of chronic heart failure. Not to be neglected is also the fact that
      GH, through its nitric oxide (NO)-releasing action, contributes to the
      maintenance of normal vascular reactivity and peripheral vascular resistance.
      This particular kind of interaction of GH with the cardiovascular system accounts
      for: (i) the lack of cardiac impairment in short-term acromegaly; (ii) the
      beneficial effects of GH and IGF-I in various models of heart failure; (iii) the
      protective effect of GH and IGF-I against post-infarction ventricular
      remodelling; (iv) the reversal of endothelial dysfunction in patients with heart
      failure treated with GH; and (v) the cardiac abnormalities associated with GH
      deficiency and their correction after GH therapy. If it is clear that GH and IGF
      I exert favourable effects on the heart in the short term, it is equally
      undeniable that GH excess with time causes pathologic cardiac hypertrophy and, if
      it is not corrected, eventually leads to cardiac failure. Why then, at one point
      in time in the natural history of acromegaly, does physiological cardiac growth
      become maladaptive and translate into heart failure? Before this transition takes
      places, the acromegalic heart shares very few features with other models of
      chronic heart failure. None of the mechanisms involved in the progression of
      heart failure is clearly operative in acromegaly, save for the presence of
      insulin-resistance and mild alterations of lipoproteins and clot factors. Is this
      enough to account for the development of heart failure? Probably not. On the
      other hand, it must be stressed that GH and IGF-I activate several mechanisms
      that play a protective role against the development of heart failure. These
      include ventricular unloading, deactivation of neurohormonal components,
      antiapoptotic effect and enhanced vascular reactivity. Ultimately, all data
      available concur to hypothesize that acromegalic cardiomyopathy represents a
      progressive model of cardiac hypertrophy in which the cardiotoxic and pro
      remodelling effect is intrinsic to the excessive and unrestrained myocardial
      growth.

PMID- 14974907
TI  - Residual goitre in the postiodization phase: iodine status, thiocyanate exposure
      and autoimmunity.
AB  - OBJECTIVE: This study was done to assess goitre prevalence, thyroid functional
      status and cause of residual goitre among school children in the postsalt
      iodization phase in India. DESIGN: A cross-sectional study in which, 14762 school
      children in the age group of 6-18 years, from different States and Union
      territories of India, were evaluated for goitre prevalence, urinary iodine and
      thiocyanate excretion, functional status of the thyroid as well as serological
      and cytopathological markers for thyroid autoimmunity. MEASUREMENTS: Urinary
      iodine (wet ashing method), urinary thiocyanate (colourimetric method), serum
      thyroxine [in-house radioimmunoassay (RIA)], serum TSH (IRMA), antithyroid
      microsomal and antithyroglobulin antibodies (haemagglutination method) were
      estimated. Fine-needle aspiration cytology was performed in all goitrous subjects
      giving consent. RESULTS: The overall goitre prevalence was 23% (27.1% girls;
      17.8% boys, P < 0.001). Subjects belonging to poor socio-economic strata had
      significantly higher goitre prevalence. Median urinary iodine excretion (UIE) in
      goitrous subjects (2-53 micromol/l) was significantly higher than in controls (2
      24 micromol/l; P < 0.001). Levels of UIE observed among goitrous subjects showed
      no relationship with the presence or absence of thyroid dysfunction or with
      thyroid antibody status. High titres (> or = 1:1600) of TMA were present more
      often in goitrous subjects (6.08%) than nongoitrous controls (0.34%; P < 0.001)
      and in girls (7.3%) than boys (2.35%; P < 0.001). TMA positivity were
      significantly more among goitrous subjects with thyroid dysfunction than in
      euthyroid subjects. Significantly higher median urinary thiocyanate (USCN)
      excretion was observed in goitrous subjects (0.75 mg/dl) compared to controls
      (0.64 mg/dl; P < 0.001) and goitrous girls compared to goitrous boys. USCN
      excretion of goitrous subjects and controls showed no relationship with
      functional or thyroid antibody status in various groups. CONCLUSIONS: Persistent,
      albeit reduced prevalence of goitre, despite adequate iodine prophylaxis,
      suggests existence of additional factors in goitrogenesis in India. Thyroid
      autoimmunity can explain only a part of the goitre prevalence. The role of
      goitrogens in residual goitre prevalence is brought forth.

PMID- 14974908
TI  - Metabolic, inflammatory and haemostatic effects of a low-dose continuous combined
      HRT in women with type 2 diabetes: potentially safer with respect to vascular
      risk?
AB  - BACKGROUND: Conventional hormone replacement therapy (HRT) containing conjugated
      equine oestrogen (CEE) and medroxyprogesterone acetate (MPA) increases
      triglyceride, C-reactive protein (CRP) and coagulation Factor VII concentrations,
      potentially explaining their increased coronary heart disease (CHD) and stroke
      risk. OBJECTIVE: To assess the metabolic effects of a continuous combined HRT
      containing 1 mg oestradiol and 0.5 mg norethisterone or matching placebo. DESIGN:
      Double-blind, randomized placebo-controlled trial. PATIENTS: Fifty women with
      type 2 diabetes. MEASUREMENTS: Classical and novel risk factors for vascular
      disease. RESULTS: Triglyceride concentration was not altered (P = 0.31, change in
      active arm relative to placebo) and low-density lipoprotein (LDL) cholesterol
      concentration declined 13% (P = 0.018). IL-6 concentration (mean difference -1.42
      pg/ml, 95% CI: -2-55 to -0-29 IU/dl, P = 0.015), Factor VII (-32 IU/dl, -43 to 
      21 IU/l, P < 0.001) and tissue plasminogen activator antigen (by 13%, P = 0.005)
      concentrations fell, but CRP was not significantly altered (P = 0.62). Fasting
      glucose (P = 0.026) also declined significantly, but there are no significant
      effects on HBA1c, Factor IX or APC resistance. CONCLUSIONS: HRT containing 1 mg
      oestradiol and 0.5 mg norethisterone may avoid the adverse metabolic effects
      potentially implicated in the elevated CHD and stroke risk induced by
      conventional higher dose HRT. This type of preparation may therefore be more
      suitable than conventional HRT for women at elevated CHD risk such as those with
      type 2 diabetes. Large randomized controlled trials of such low dose
      preparations, powered for cardiovascular end points, are now needed.

PMID- 14974909
TI  - Modulation by progestogens of the effects of oestrogen on hepatic endocrine
      function in postmenopausal women.
AB  - OBJECTIVE: Oral but not transdermal oestrogen administration reduces IGF-I, and
      increases GH binding protein (GHBP) reflecting effects on hepatic endocrine
      function in postmenopausal women. As progestogens attenuate the effects of
      oestrogen on circulating lipid levels according to their androgenic properties,
      we have investigated the impact of progestogen types on the hepatic endocrine
      effects of oestrogen. DESIGN: Four progestogens differing in androgenicity were
      co-administered in a monthly cyclical regimen in random order to postmenopausal
      women receiving either oral (n = 9, premarin 1.25 mg) or transdermal (n = 10,
      Estraderm 100 microg patches twice weekly). The four progestogens were
      cyproterone acetate (CA 5 mg, antiandrogenic), dydrogesterone (20 mg, neutral),
      medroxyprogesterone acetate (MPA 10 mg, mildly androgenic), norethisterone (2.5
      mg, androgenic). PATIENTS: Nineteen postmenopausal women (age 57 +/- 3 years,
      mean +/- SE) were studied. MEASUREMENTS: The effects of oestrogen alone and the
      combined effects with each progestogen type on IGF-I, GHBP, SHBG, cholesterol,
      triglycerides and lipoprotein(a) were investigated. RESULTS: Mean IGF-I fell
      while GHBP and SHBG levels increased with oral (P < 0.01) but not transdermal
      oestrogen administration. When the combined effects were examined, progestogens
      did not affect IGF-I, GHBP and SHBG during oral oestrogen treatment, while they
      significantly increased (P < 0.01) mean IGF-I levels during transdermal therapy.
      Among the progestogen types, only norethisterone prevented the fall in IGF-I
      induced by oral oestrogen. During transdermal therapy, MPA and norethisterone but
      not CA or dydrogesterone significantly increased (P < 0.005) IGF-I. The rise in
      GHBP induced by oral oestrogens tended to be lower during co-administration of
      MPA and norethisterone. The increase in SHBG induced by oral oestrogen was
      attenuated (P < 0.05) by norethisterone which was the only progestogen that
      lowered SHBG (P < 0.05) during transdermal oestrogen treatment. Mean IGF-I was
      higher (P < 0.001), GHBP and SHBG lower during co-administration of androgenic
      progestogens (MPA and norethisterone). CONCLUSIONS: Oestrogen effects on IGF-I,
      GHBP and SHBG are dependent on the route of administration with progestogens
      having variable effects. Among the progestogen types, norethisterone, the most
      androgenic, had the greatest effect, particularly on IGF-I. Progestogens modulate
      the effects of oestrogen on hepatic endocrine function in relation to their
      intrinsic androgenic properties. The modulatory effects of progestogens on IGF-I
      during oestrogen therapy may have long-term implications for lean body mass.

PMID- 14974910
TI  - Increased IGF-I : IGFBP-3 ratio in patients with hepatocellular carcinoma.
AB  - BACKGROUND: The development of hepatocellular carcinoma in liver cirrhosis is
      associated with altered synthesis and secretion of several growth factors. AIM:
      The aim of this prospective study was to investigate the potential implication of
      IGF-I and its major binding protein (IGFBP-3) in the development of
      hepatocellular carcinoma. PATIENTS AND METHODS: IGF-I and IGFBP-3 were measured
      in 150 healthy subjects, 40 patients with liver cirrhosis and 63 with liver
      cirrhosis and untreated hepatocellular carcinoma. The ratio between IGF-I and
      IGFBP-3 was also calculated. RESULTS: Serum IGF-I (70 +/- 10 and 65 +/- 7 vs. 185
      +/- 6.4 microg/l, P < 0.001) and IGFBP-3 levels (1225 +/- 113 and 984 +/- 67 vs.
      3017 +/ -80 microg/l, P < 0.001) were lower in patients with liver cirrhosis,
      without or with hepatocellular carcinoma, than in controls. Age was negatively
      correlated with IGF-I levels in patients with liver cirrhosis (r = -0.6; P =
      0.0002) as well as in controls (r = -0.8, P < 0.0001), but not in patients with
      hepatocellular carcinoma (r = -0.2; P = 0.2). Additionally, in patients with
      liver cirrhosis (r = -0.54; P = 0.0003) and more weakly in those with
      hepatocellular carcinoma (r = -0.24; P = 0.04) IGF-I levels were negatively
      correlated with liver failure measured according with Child class. Despite
      patients with class C hepatocellular carcinoma being older than those in the same
      functional class with cirrhosis (64 +/- 2 vs. 57 +/- 12 years, P < 0.01), they
      had a significantly increased IGF-I : IGFBP-3 ratio (0.18 +/- 0.05 vs. 0.41 +/-
      0.09, P = 0.04), due mostly to increased IGF-I levels (27.1 +/- 5.6 vs. 42 +/-
      6.2 microg/l) as IGFBP-3 levels were similar to patients with cirrhosis (734 +/-
      81 vs. 679 +/- 83 microg/l). CONCLUSIONS: Hepatocellular carcinoma is associated
      with a higher IGF-I : IGFBP-3 ratio than that found in patients with liver
      cirrhosis and a similar degree of liver failure.

PMID- 14974911
TI  - Fine analysis of the short arm of chromosome 1 in sporadic and familial
      pheochromocytoma.
AB  - OBJECTIVE: Despite the very recent discovery that about 25% of apparently
      sporadic forms of pheochromocytoma are actually due to germline mutations of RET,
      VHL, SDHB or SDHD genes, the genetic bases of the tumourigenesis of this type of
      cancer are still incompletely understood. Recent studies provided evidence that a
      new tumour suppressor gene, mapping on the short arm of chromosome 1, could be
      involved in early tumourigenesis of pheochromocytoma. DESIGN: We have performed a
      fine analysis of loss of heterozygosity (LOH) of this region. In particular, we
      have analysed 31 highly polymorphic microsatellites distributed at 3.8 Mege base
      (Mb) mean intervals along the short arm of the chromosome 1 in paired samples of
      DNA extracted from peripheral blood lymphocytes and tumour tissues. PATIENTS: The
      study was carried out on 38 patients with pheochromocytoma that had been grouped,
      by careful clinical and molecular investigation, in the following classes: 21
      sporadic, five multiple endocrine neoplasia type 2 (MEN2), two type 1
      neurofibromatosis (NF1), five von Hippel-Lindau (VHL), one somatic VHL mutated
      and four nonsyndromic familial cases. RESULTS: In 12/21 sporadic cases (57.1%),
      in 4/5 MEN2 (80%), 2/4 non-syndromic familial cases (50%), and in 2/2 NF1 (100%),
      the entire short arm was deleted, while in 6/21 sporadic (28.6%) and 1/5 MEN2
      (20%) cases a partial deletion was detected. On the other hand, none of the five
      cases due to VHL mutation (either germline or somatic) had LOH at chromosome 1.
      In total, complete or partial deletion of 1p was detected in 27/38 (71%) of the
      cases. The most frequently deleted marker was D1S2890, which maps at 1p32.1. This
      region, which spans from 50 to 62 Mb from telomere, was therefore further
      investigated with markers located at a mean interval of 1.3 Mb in the subset of
      cases that showed a partial deletion of 1p. This analysis showed that a small
      region between 55.1 and 59.0 Mb was most frequently missing, which could
      therefore contain a novel pheochromocytoma locus. CONCLUSIONS: The results
      presented here confirm that the short arm of chromosome 1 harbours one or more
      genes responsible for the development of pheochromocytoma and suggest that one of
      them could map in a 3.9-Mb fragment between 1p32.3 and 1p32.1.

PMID- 14974912
TI  - Serum leptin levels in patients with premenstrual syndrome treated with GnRH
      analogues alone and in association with tibolone.
AB  - OBJECTIVE: Leptin seems to regulate reproductive function and it has been
      hypothesised that its secretion may be induced by oestrogens. Changes in its
      levels has been advocated as a determinant in the pathogenesis of premenstrual
      syndrome (PMS). We evaluated serum leptin levels in patients affected by PMS and
      in controls to establish: (i) if induced hypoestrogenism has an impact on leptin
      concentrations; (ii) if the administration of tibolone modifies the effects of
      hypoestrogenism on serum leptin levels; and (iii) if the improvement in PMS
      symptomatology can be correlated to changes in serum leptin levels. DESIGN:
      Prospective, randomized study. PATIENTS: Twenty-eight women affected by PMS and
      20 unaffected controls. Affected patients were randomly assigned to two groups to
      receive leuprolide acetate (3.75 mg intramuscularly) plus tibolone (2.5 mg/day)
      (group A; n = 14) or plus placebo (group B; n = 14), at the onset of the
      vasomotor symptoms. MEASUREMENTS: Serum leptin, oestradiol and progesterone
      levels, PMS signs and symptoms evaluated during a 2 months' pretreament period
      and after 2 months of therapy. RESULTS: No differences in leptin levels among the
      three groups and within the same group at all time evaluated were observed.
      Oestradiol and progesterone concentrations were significantly lower in all groups
      during treatment in comparison with pretreatment values. Before therapy, leptin
      levels were positively correlated both with oestradiol and progesterone in the
      follicular and luteal phase in all groups. This correlation was lost after
      treatment. All PMS patients showed a significant improvement of the
      symptomatology. CONCLUSIONS: Hypoestrogenism induced by GnRH analogues (GnRHa)
      does not seem to influence leptin levels in normal women and those with PMS, and
      the addition of tibolone does not impact on these levels. Because PMS
      symptomatology did significantly improve during treatment with GnRHa alone, or in
      associtation with tibolone, it is unlikely that changes in leptin levels could
      have an important role in the pathophysiology of PMS.

PMID- 14974913
TI  - Vasoactive intestinal peptide (VIP): a new neuroendocrine marker of clinical
      progression in chronic heart failure?
AB  - OBJECTIVE: Vasoactive intestinal peptide (VIP) is a powerful vasodilatory
      neuropeptide with positive inotropic and chronotropic properties. The aim of the
      study was to investigate the pathophysiological role of VIP in heart failure.
      DESIGN AND RESULTS: VIP was assayed in plasma within the first in-hospital day in
      52 patients with heart failure due to dilated cardiomyopathy. The concentration
      of VIP was: (i) higher in patients than in healthy subjects; (ii) higher in
      elderly but not in younger patients compared with healthy controls; (iii)
      inversely related to NYHA class: higher in NYHA 2 than in NYHA > 2 patients and
      in normal subjects, in both young and elderly groups; (iv) not correlated with
      echocardiographic parameters and (v) not influenced by the aetiology of dilated
      cardiomyopathy. CONCLUSIONS: The physiological properties of VIP suggest that the
      increased plasma concentrations in patients with heart failure contribute to
      restore the compromised haemodynamic balance either by improving myocardial
      performance or by counteracting the harmful effects related to simultaneous
      activation of other neuroendocrine systems, i.e. the sympathetic and renin
      angiotensin systems. Decreased VIP concentrations are related to progressive
      worsening of heart failure. The higher VIP concentrations in elderly patients
      compared with healthy controls suggest that the capacity to increase VIP
      production is preserved in older people.

PMID- 14974914
TI  - Genetic analysis of mitochondrial complex II subunits SDHD, SDHB and SDHC in
      paraganglioma and phaeochromocytoma susceptibility.
AB  - BACKGROUND: Germline mutations in three subunits of mitochondrial complex II
      (SDHB, SDHC and SDHD) may be associated with susceptibility to phaeochromocytoma
      (PC) and/or head and neck paraganglioma (HNPGL). METHODS: To further define the
      role of SDH subunit mutations in these disorders, we analysed a series of 22
      probands with PC and evidence of genetic susceptibility (seven with familial PC
      only, one with familial PC and HNPGL, 10 sporadic cases with multiple PC and four
      cases of isolated paediatric onset PC) for germline SDHB, SDHC and SDHD
      mutations. In addition, we analysed 34 cases of HNPGL (30 isolated cases with
      single tumours, three isolated cases with multiple tumours and one familial case
      with multiple tumours) for somatic and germline mutations in SDHB, SDHC and SDHD.
      RESULTS: We identified four germline mutations (three SDHB and one SDHD, three
      novel) in the 22 PC probands. Combining these results with our previous series,
      we have detected germline SDHB or SDHD mutations in 2/12 (17%) of familial PC
      only kindreds, 4/5 (80%) of familial PC and HNPGL cases, 1/10 of sporadic
      multiple PC cases and 2/4 (50%) of paediatric PCs. No somatic mutations were
      detected in the HNPGL tumours, but four cases with multiple HNPGL had the common
      P81L germline SDHD mutation. Intriguingly a silent SNP (c.204C > T) in SDHD was
      significantly more common in HNPGL cases (6/34) than in controls (1/100, P =
      0.0011). Combining our results with those from two other large studies in which
      both SDHB and SDHD have been analysed, SDHB mutations were most commonly
      associated with phaeochromocytoma susceptibility and SDHD with the development of
      HNPGL (P = 0.025). However, germline SDHB and SDHD mutations demonstrate
      considerable phenotypic variability and genotype-phenotype correlations are
      complex. CONCLUSION: The significantly lower frequency (P = 0.028) of germline
      SDH subunit mutations in familial PC only cases compared to those with familial
      PC and HNPGL suggests that further PC susceptibility gene(s) remain to be
      identified.

PMID- 14974915
TI  - Thyroid cancer immuno-therapy with retroviral and adenoviral vectors expressing
      granulocyte macrophage colony stimulating factor and interleukin-12 in a rat
      model.
AB  - BACKGROUND: Introduction of genes encoding immuno-stimulatory cytokine(s) into
      cancer cells is well known to enhance anti-tumour immunity. AIM: The present
      studies were designed to evaluate the therapeutic efficacy of retroviral- and
      adenoviral-mediated delivery of IL-12 and/or granulocyte macrophage colony
      stimulating factor (GM-CSF) genes for thyroid cancer in an immuno-competent rat
      model. METHODS: A rat thyroid cancer cell line FRTL-Tc syngeneic to Fisher rat
      was used. RESULTS: Expression of these exogenous cytokines did not affect in
      vitro cell growth. Subcutaneous injection of FRTL-Tc cells retrovirally
      transduced with IL-12 or GM-CSF genes formed significantly smaller tumours than
      that of the parental cells, but had little effect on growth of distant tumours,
      suggesting no vaccine effect. Similarly, injection of the cells infected with
      adenovirus expressing IL-12 or GM-CSF (AdIL-12 or AdGM-CSF) almost completely
      abolished tumourigenicity and injection of AdGM-CSF into pre-established tumours
      significantly inhibited growth of the tumours injected; neither, however, showed
      a systemic vaccine affect. On the other hand, injection of AdIL-12 into the pre
      established tumours significantly inhibited growth of not only the tumours
      injected but also distant tumours, indicating induction of systemic anti-tumour
      immunity. Serum IL-12 was detectable only in this approach. There was neither a
      synergistic or additive effect of these two cytokines. CONCLUSIONS: Our data
      demonstrate in a rat thyroid cancer model that only injection of AdIL-12 into the
      pre-established tumours elicited systemic anti-tumour immunity, but injection of
      AdGM-CSF or injection of the cells expressing IL-12 or GM-CSF elicited only local
      effect, indicating that in situdelivery of IL-12 gene with adenovirus appears
      most efficacious but may still require adjuvant modalities to enhance the anti
      tumour effect.

PMID- 14974916
TI  - Acquired prolactin deficiency indicates severe hypopituitarism in patients with
      disease of the hypothalamic-pituitary axis.
AB  - OBJECTIVE: Prolactin deficiency has been the subject of many scientific studies,
      but there is a paucity of information regarding prolactin deficiency in humans.
      In this report, adults with disease of the hypothalamic-pituitary axis (HPA) were
      studied to determine the prevalence of severe acquired prolactin deficiency (APD)
      and the pathophysiological characteristics associated with it. PATIENTS AND
      METHODS: APD was defined as a serum prolactin level persistently below the
      detection limit of the assay, i.e. less than 50 mU/l (normal range: male 85-444,
      female 85-530). Patients with a diagnosis of acromegaly, prolactinoma or with
      congenital or drug induced prolactin deficiency were excluded. Three hundred and
      sixty-nine patients (190 women, age range 17-79 years) with disease of the HPA,
      meeting the specified criteria were identified. RESULTS: Twenty-two (13 women,
      age range 29-76 years), showed evidence of APD. Thirteen of the 22 patients with
      APD had been treated for Cushing's disease. In all, 62 patients treated for
      Cushing's disease were identified, resulting in a prevalence of APD in treated
      Cushing's disease of 20.97%. Excluding treated Cushing's disease, the prevalence
      of APD in the remainder of the cohort was 2.93%. Nineteen patients with APD
      (86.4%) and 183 without APD (52.7%) underwent surgery in the region of the HPA (P
      = 0.0042). In contrast, nine patients with APD (40.9%) and 283 without APD
      (80.4%) had received radiotherapy, with fields which included the HPA (P <
      0.001). No patient with isolated APD was identified. All patients with APD had
      evidence of severe GH deficiency (GHD) with a peak GH response to provocative
      stimuli of < 1.6 mU/l and a median IGF-I standard deviation score (SDS) of -4.85
      (quartiles -9.56 to -2.80). Of the 13 patients with APD and Cushing's disease,
      all were gonadotrophin and TSH-deficient, six were adrenocorticotropic hormone
      (ACTH)-deficient and six (46.1%) had cranial diabetes insipidus (CDI). Of the
      remaining nine patients with APD, total anterior pituitary hormone failure was
      present in all and CDI was present in two (22.2%). CONCLUSIONS: The presence of
      APD indicates severe hypopituitarism in adults with HPA disease. It is
      universally associated with severe GHD. It is more common after surgery to the HP
      region. It has a low overall prevalence except in patients surgically treated for
      Cushing's disease.

PMID- 14974917
TI  - The androgen receptor gene CAG polymorphism is associated with the severity of
      coronary artery disease in men.
AB  - OBJECTIVE: The role of androgens in the pathogenesis of coronary artery disease
      (CAD) remains controversial. The length of the polyglutamine stretch of the
      transactivation domain (CAG repeat) of the androgen receptor (AR) inversely
      affects androgen activity. The aim of this study was to investigate the effect of
      this polymorphism of the AR gene in the extent of CAD in male patients. DESIGN
      AND PATIENTS: The relationship of the length of the AR gene CAG repeat on the
      severity of CAD was examined in 131 men (36-86 years old) undergoing coronary
      angiography. MEASUREMENTS: The severity of CAD was assessed by the number (0-3)
      of coronary vessels with > 50% reduction in the luminal diameter. The interaction
      of the AR gene polymorphism with the intima media thickness (IMT) of peripheral
      arteries and serum levels of sex steroids, insulin and biochemical parameters
      were also studied. RESULTS: The upper quartile of CAG length (range 9-30) was >
      or = 23 repeats (longAR). The mean body mass index (BMI) of patients with shorter
      repeats (< 23; shortAR) was significantly lower than in men with longAR (26.1 vs.
      27.6, respectively; P = 0.043 M-W Rank test). There was no correlation between
      the AR gene repeat length and serum testosterone. Oestradiol levels were
      significantly higher in longAR (0.19 +/- 0.08 nmol/l vs. 0.14 +/- 0.07 in
      shortAR, P = 0.031). This difference was independent of BMI. Men with shortAR had
      significant CAD (i.e. one to three arteries with stenosis) more frequently
      (79.5%) than men with longAR (20.5%); of the subjects with stenosis in no
      arteries, 56.5% had shortAR and 43.5% longAR (chi2 = 4.3, P = 0.038). This
      association was independent of age and BMI. The IMT of peripheral arteries, lipid
      parameters, basal insulin resistance, blood pressure and family history for early
      CAD, did not differ according to AR length. CONCLUSIONS: The shorter CAG repeat
      of the AR gene is associated with more severe CAD, which suggests a role for the
      sensitivity to androgens in the increased frequency of CAD in males. In addition,
      a protective role of endogenous oestrogen, which is higher in the longAR
      subgroup, can contribute to the observed difference.

PMID- 14974918
TI  - Fasting insulin sensitivity and post-oral glucose hyperinsulinaemia related to
      cardiovascular risk factors in adolescents with precocious pubarche.
AB  - OBJECTIVE: Adolescents and young women with a history of precocious pubarche (PP,
      appearance of pubic hair before 8 years) exhibit hyperlipidaemia, and ovarian
      hyperandrogenism, indicating increased risk of coronary heart disease in the long
      term. The aim of this study was to determine the relative contribution of fasting
      insulin sensitivity, and post oral glucose tolerance test (OGTT) measures of
      insulin secretion to metabolic risk markers of adult disease. PATIENTS AND
      DESIGN: We have analysed data from 51 young women presenting with isolated PP
      (age range, 5.9-19.0 years) in early, mid and late puberty and 68 puberty-matched
      controls (age range, 6.2-16.8 years). Body composition data from a further 67
      girls with PP are also presented. MEASUREMENTS: The homeostasis model of
      assessment insulin sensitivity index (HOMA Si) based on fasting glucose and
      insulin measurements and MSI120 based on insulin levels over the first 120 min
      following standard oral glucose load were selected as measures of fasting insulin
      sensitivity and 0-120-min insulinaemia, respectively. ISI30 was used as an index
      of insulin secretion 30 min following oral glucose load. RESULTS: The
      physiological decrease in fasting insulin sensitivity, 30-min insulin secretion
      and 0-120-min insulinaemia during puberty were exaggerated in PP girls. The
      relationship between fasting insulin sensitivity and 0-120-min insulinaemia was
      similar in PP girls and in controls but at each level of fasting insulin
      sensitivity the PP girls had a higher level of insulin secretion in response to
      an oral glucose load (P < 0.001). Fasting insulin sensitivity and 0-120 minute
      insulinaemia but not 30-min insulin secretion were strongly related to known
      cardiovascular risk factors. In a multivariate model incorporating fasting
      insulin sensitivity, 0-120-min insulinaemia, pubertal stage and body mass index
      (BMI) SDS as covariates, 0-120-min insulinaemia was strongly associated with
      elevated free androgen index, total cholesterol and truncal fat mass (P < 0.001)
      whereas fasting insulin sensitivity was associated only with reduced free
      androgen index (P < 0.02). CONCLUSIONS: Chronic exposure to insulin as reflected
      by 0-120 min hyperinsulinaemia, rather than 30 min insulin secretion, or fasting
      insulin senstivity, was most closely related cardiovascular disease risk in girls
      with PP.

PMID- 14974919
TI  - Reduced exercise capacity in untreated adults with primary growth hormone
      resistance (Laron syndrome).
AB  - OBJECTIVE: Primary IGF-I deficiency (Laron syndrome, LS) may decrease exercise
      capacity as a result of a lack of an IGF-I effect on heart, peripheral muscle or
      lung structure and/or function. METHODS: Eight patients (six females) who had
      never received treatment with IGF-I, with mean age of 36 +/- 10 (SD) years (range
      21-48), weight 47 +/- 9 kg (31-61), height 126 +/- 12 cm (112-140) and body mass
      index of 29 +/- 4 kg/m2 (24-34), and 12 age-matched controls, underwent lung
      function tests and incremental cycling to the limit of tolerance (CPX,
      MedGraphics). Predicted values for the patients were derived from adult equations
      based on height. RESULTS: In LS patients, lung function was near normal; vital
      capacity was 84 +/- 11% of expected (66-103). Peak exercise O2-uptake and the
      anaerobic threshold were reduced, 57 +/- 20% of predicted and 33 +/- 9% of
      predicted peak (P = 0.005 vs. controls), despite normal mean exercise breathing
      reserve. All parameters were normal in the controls. CONCLUSION: Exercise
      capacity in untreated adults with LS is significantly reduced. The limitation for
      most patients was not ventilatory but resulted either from low cardiac output
      and/or from dysfunction of the peripheral muscles. However, the relative
      contribution of each of these elements and/or the role of poor fitness needs
      further study.

PMID- 14974920
TI  - Fibrous bodies are associated with lower GH production and decreased expression
      of E-cadherin in GH-producing pituitary adenomas.
AB  - OBJECTIVE: A retrospective study was conducted in order to elucidate the
      clinicopathological significance of fibrous bodies, a hallmark of the sparsely
      granulated variant of GH-producing pituitary adenomas. METHODS: A total of 37
      acromegalic patients, 14 men and 23 women, with pure GH adenomas were studied.
      Immunohistochemistry was performed with antibodies specific for cytokeratin 8 and
      18 (CAM5.2), GH, prolactin and E-cadherin. The tumour volume was estimated with
      high-resolution magnetic resonance imaging. RESULTS: The percentages of adenoma
      cells with dot-like immunoreactivity for CAM5.2, fibrous bodies, were variable,
      ranging continuously from 0 to 100%. An increased percentage was associated with
      a lower basal GH level per unit tumour volume, a lower GH response to a
      bromocriptine suppression test, decreased immunoreactivities for GH and
      prolactin, and a decreased expression of E-cadherin immunoreactivity. CONCLUSION:
      GH adenomas could not be distinctly separated into those with or without fibrous
      bodies. Decreased expression of E-cadherin may be involved in formation of
      fibrous bodies and result in lower GH production.

PMID- 14974921
TI  - Determinants of IGF-I status in a large cohort of growth hormone-deficient (GHD)
      subjects: the role of timing of onset of GHD.
AB  - BACKGROUND: IGF-I standard deviation score (SDS) is widely used in clinical
      practice; however, factors determining IGF-I SDS in GH-deficient (GHD)
      individuals remain incompletely understood. Earlier studies have been limited by
      the small size of cohorts studied. We have used the KIMS database to examine if a
      true difference exists between subjects who developed GHD in adult life (AO), and
      those who developed GHD in childhood (CO). PATIENTS: A total of 1317 patients
      fulfilled the inclusion criteria, 1073 with AO GHD and 244 with CO GHD. METHODS:
      Serum IGF-I concentrations were determined by a hydrochloric acid-ethanol
      extraction radioimmunoassay method using synthetic IGF-I for labelling. The
      reference range was calculated using normative data from healthy Swedish
      individuals. RESULTS: A total of 86% of patients with CO GHD but only 52% of
      patients with AO GHD had IGF-I SDS below -2 SDS. The CO cohort had a lower IGF-I
      SDS (-4.69 vs. -2.24, P < 0.0001), a smaller body mass index (BMI; 26.6 vs. 28.6
      kg/m2, P < 0.0001) and waist-hip ratio (WHR; 0.90 vs. 0.92 P < 0.001) than the AO
      cohort. A stepwise multiple linear regression was performed to examine the
      principal determinants of IGF-I SDS. Age at onset of GHD was the most important
      determinant of IGF-I SDS, contributing 17% towards the variability of IGF-I SDS.
      Timing of onset, gender, BMI, and number of pituitary hormone deficiencies other
      than GH deficiency were also significant determinants of IGF-I SDS. CONCLUSION:
      Whilst age at onset of GHD was the most important determinant of IGF-I SDS,
      individuals with CO GHD had values on average 1.43 lower than those with AO GHD,
      all other factors being equal. Potential explanations include differences in GH
      secretory patterns, variation in body composition, and/or suboptimal treatment of
      GHD in childhood.

PMID- 14974922
TI  - GH treatment and its effect on bone mineral density, bone maturation and growth
      in short children born small for gestational age: 3-year results of a randomized,
      controlled GH trial.
AB  - BACKGROUND: To investigate in a group of short children born small for
      gestational age (SGA), the effects of 3 years of GH treatment vs. no treatment on
      bone age (BA), height and bone mineral density (BMD). Also, to evaluate the
      influence of the severity of growth retardation at start and the GH dose on the
      gain in height. PATIENTS AND METHODS: The study design was an open-labelled,
      controlled multicentre GH study for 3 years. Non-GH-deficient (GHD) children (n =
      87) were randomized to either a GH group (n = 61) or an untreated control group
      (n = 26). In addition, 12 SGA children had GHD (GHD group) and were treated in
      parallel. Both the GH and the GHD group were treated with a GH dose of 33
      microg/kg/day. BMD was evaluated using dual energy X-ray absorptiometry (DEXA).
      In addition, data of our first GH trial in which short SGA children were treated
      with a GH dose of 66 microg/kg/day (n = 24) were used for comparison of height
      gain. RESULTS: In contrast to the control group, the GH group showed a
      significant increase in height (P < 0.001), as did the parallel GHD group. Bone
      maturation [delta bone age (BA)/delta calendar age (CA)] increased significantly
      during the first 2 years of GH treatment but slowed-down thereafter. The 3-year
      deltaBA/deltaCA ratio correlated significantly with the gain in height (r = 0.6,
      P < 0.001). At start, mean BMD SDS and mean BMAD SDS were significantly lower
      than zero. During GH treatment both increased impressively (P < 0.001). The gain
      in height of children with severe short stature at start (< or = -3.00 SDS), did
      not differ between those receiving either a GH dose of 33 or 66 microg/kg/day.
      CONCLUSION: Three years of GH treatment in short children born SGA results in a
      normalization of height during childhood. Also, bone maturation increased
      proportionately to the height gain. At start, mean values of BMD and BMAD were
      significantly reduced but normalized during GH treatment. We did not find an
      indication to treat very short SGA children (H SDS < or = -3.00) with a higher GH
      dose. We rather suggest to start GH treatment at an early age in order to achieve
      a normal height before puberty starts.

PMID- 14974923
TI  - Acromegalic features in growth hormone (GH)-deficient patients after long-term GH
      therapy.
AB  - BACKGROUND: Craniofacial, hand, foot and somatic growth depend on normal GH
      secretion. Acromegalic features have been described in children with GH
      insensitivity after IGF-I treatment. We observed patients with acromegalic
      features such as increase of foot size, nose and jaw enlargement among our cases
      with GH deficiency, treated with standard recombinant (rh)GH doses. The aim of
      our study was to analyse the possible factors involved in the development of
      acromegalic features in these patients. PATIENTS: We evaluated 21 patients, 17
      with combined pituitary hormone deficiency and four with isolated GH deficiency
      treated with rhGH (0.05-0.15 U/kg/day, sc, at night) for 2-12 years who achieved
      final height. IGF-I and IGFBP-3 were measured before and every 6 months during
      therapy and bone age was evaluated yearly. At the end of therapy, patients' hand
      and foot sizes and height were measured and plotted on nomograms for hand
      according to height and age, and foot size according to height. Lateral
      radiographs of the face were performed to obtain the linear measurement of the
      lower jaw length. RESULTS: Foot size was greater than 97th percentile in 8/21
      patients and lower jaw length was greater than +2SD in 4/21 patients. Patients
      were classified in two groups: group 1 (with foot size greater than 97th
      percentile and/or lower jaw length greater than +2SD) consisted of 11 patients
      (six females); nine had combined pituitary hormone deficiency (six associated to
      hypogonadotrophic hypogonadism) and three had isolated GH deficiency; group 2
      (with foot size smaller than 97th percentile and lower jaw length less than +2SD)
      consisted of 10 patients (seven boys); nine had combined pituitary hormone
      deficiency (six associated to hypogonadotrophic hypogonadism) and one with
      isolated GH deficiency. During treatment, IGF-I levels ranged from < or = 3 to
      +2SD and IGFBP-3 levels ranged from -3 to +2SD, in both groups. We observed no
      statistically significant differences between the two groups regarding
      chronological age, bone age, height at the beginning and at the end of therapy,
      pubertal development, duration of rhGH treatment and IGF-I and IGFBP-3 levels (P
      > 0.05). Foot size percentile exceeded final height percentile in 11/21 patients
      (seven girls). CONCLUSION: Long-term rhGH treatment with standard doses might be
      associated with acromegalic features (increased foot size and lower jaw
      measurements) in patients with GH deficiency who achieved final height,
      especially in girls. Neither the clinical nor the hormonal parameters, IGF-I and
      IGFBP-3 levels, were useful to predict the development of these features. Further
      studies are necessary to analyse the frequency of this side-effect and how to
      prevent it.

PMID- 14974924
TI  - Octreoscan in patients with bronchial carcinoid tumours.
AB  - OBJECTIVES: Scintigraphy with radiolabelled octreotide (octreoscan) is useful for
      imaging various neuroendocrine tumours, especially in patients with midgut
      carcinoids. We were interested in estimating the efficacy of octreoscan for
      detection of the primary tumour and metastases in patients with bronchial
      carcinoids. PATIENTS AND METHODS: Twenty-eight patients with histologically
      verified bronchial carcinoids underwent octreoscan and the imaging results were
      compared to CT regarding soft tissue metastases, and to bone scan and MRI
      regarding bone metastases. The primary tumour had been removed prior to the
      octreoscan in 12 patients. Metastatic disease was diagnosed in 22 patients.
      RESULTS: Altogether, 20 patients (71%) had octreoscan-positive tumours, including
      2/5 patients with ectopic ACTH secretion resulting in Cushing's syndrome and 8/9
      patients with carcinoid syndrome. The primary tumour was octreoscan-positive in
      13/16 patients and could be detected on CT in 15/16 patients. CT failed to
      localize the primary tumour in one octreoscan-positive patient, presenting with
      ectopic ACTH secretion and Cushing's syndrome. Intrathoracic
      recurrences/metastases were visualized by octreoscan in 7/9 patients and by CT in
      8/9 patients. CT showed liver metastases in 14 patients; nine of these patients
      (64%) had octreoscan-positive liver metastases. Ten patients had bone metastases;
      octreoscan was positive in seven and bone scan in nine of these 10. CONCLUSIONS:
      Octreoscan may be used for follow-up and detection of recurrent disease in
      patients with somatostatin receptor-positive bronchial carcinoids. In our limited
      patient material, CT however, seems to be better than octreoscan for
      visualization of the primary tumour as well as liver metastases.

PMID- 14974925
TI  - A dose-response study of salivary cortisol after dexamethasone suppression test
      in Cushing's disease and its potential use in the differential diagnosis of
      Cushing's syndrome.
AB  - OBJECTIVE: A dose-response study with different doses of dexamethasone (dex) to
      assess the corticotrophic resistance in Cushing's disease (CD) using salivary
      cortisol as an end point has not yet been evaluated. We also reported our
      experience with salivary cortisol compared to plasma cortisol determination
      during dex suppression test (DST) and after ovine corticotrophin release hormone
      (oCRH) test in the differential diagnosis of Cushing's syndrome (CS). DESIGN: We
      studied 46 patients with CS, including 28 patients with CD, 16 with adrenal
      disease and two with occult ectopic adrenocorticotropic hormone (ACTH) tumours.
      Salivary cortisol was compared to plasma cortisol and ACTH during a DST 2 mg for
      2 days, 8 mg for 2 days and 24 mg for 1 day, and after oCRH test. RESULTS: We
      observed a dose-dependent suppression of salivary cortisol, plasma cortisol and
      ACTH in CD patients. Salivary cortisol presented a higher percentage of
      suppression than plasma cortisol: 42% vs. 15% (P < 0.002), 82% vs. 67% (P <
      0.002) and 90% vs. 83% (P < 0.03) after 2, 8 and 24 mg/day dex, respectively. The
      lowest percentage of suppression was observed for plasma ACTH. The parallelism of
      these lines identified that the criterion of 65% suppression of salivary cortisol
      corresponding to 50% suppression of plasma cortisol after 8 mg/day for 2 days is
      consistent with CD. The sensitivity and specificity using 50% suppression for
      plasma cortisol were 81% and 83%, respectively, for 8 mg DST. Using the criterion
      of 65% suppression of salivary cortisol, the sensitivity and specificity were 86%
      and 100%, respectively, for 8 mg DST. After oCRH test the sensitivity and
      specificity were 86% and 91%, respectively, for ACTH, 100% and 64%, respectively,
      for plasma cortisol and 93% and 91%, respectively, (20% of increment) or 86% and
      100%, respectively, (35% increment) for salivary cortisol. CONCLUSION: In
      conclusion, salivary cortisol presents more profound suppression than plasma
      cortisol or ACTH in a dose-response pattern after different doses of dex in
      patients with CD. In addition, our data suggest that measurement of salivary
      cortisol might improve the DST as compared to plasma cortisol in the differential
      diagnosis of CS.

PMID- 14974926
TI  - Recombinant hGH replacement therapy and the hypothalamus-pituitary-thyroid axis
      in children with GH deficiency: when should we be concerned about the occurrence
      of central hypothyroidism?
AB  - OBJECTIVE: Recombinant hGH treatment may alter thyroid hormone metabolism and we
      have recently reported that 50% of patients with GH deficiency (GHD) due to
      organic lesions, previously not treated with thyroxine, developed hypothyroidism
      during treatment with recombinant human GH (rhGH). These results prompted us to
      evaluate the impact of rhGH treatment on thyroid function in children with GHD.
      DESIGN: Open study of GH treatment up to 12 months. Investigations were performed
      at baseline, and after 6 and 12 months of GH therapy. MEASUREMENT AND STUDY
      SUBJECTS: Serum TSH, FT4, FT3, AbTg and AbTPO, IGF-I, height and weight, were
      evaluated in 20 euthyroid children (group A) with idiopathic isolated GHD and in
      six children (group B) with multiple pituitary hormone deficiencies (MPHD) due to
      organic lesions. Among the latter, four already had central hypothyroidism and
      were on adequate LT4 replacement therapy, while two were euthyroid at the
      beginning of the study. RESULTS: Serum IGF-I levels normalized in all patients.
      In both groups, a significant reduction in FT4 levels (P < 0.01) occurred during
      rhGH therapy. No patient in group A had FT4 values into the hypothyroid range,
      while in four of six patients in group B, fell FT4 levels into the hypothyroid
      range during rhGH. In particular, the two euthyroid children developed central
      hypothyroidism during rhGH treatment, and their height velocities did not
      normalize until the achievement of euthyroidism through appropriate LT4
      substitution. No variation in serum FT3 and TSH levels was recorded in either
      groups. CONCLUSION: Contrary to that observed in patients with MPHD, rhGH
      replacement therapy does not induce central hypothyroidism in children with
      idiopathic isolated GHD, further supporting the view that in children with MPHD,
      as in adults, GHD masks the presence of central hypothyroidism. Slow growth (in
      spite of adequate rhGH substitution and normal IGF-I levels) is an important
      clinical marker of central hypothyroidism, therefore a strict monitoring of
      thyroid function is mandatory in treated children with MPHD.

PMID- 14974927
TI  - Prolonged psychological stress suppresses cortisol secretion.
AB  - OBJECTIVE: Response to acute psychological stress is characterized by activation
      of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous
      system. However, response to the prolonged psychological stress is less well
      known. DESIGN: This study was designed as a prospective assessment of cortisol
      secretion during prolonged psychological stress induced by continuous air raids
      and after elimination of the stress-inducing factor. SUBJECTS: The study group
      consisted of five healthy subjects (34-39 years). MEASUREMENTS: Psychological and
      endocrine (morning cortisol and 1 microg ACTH test) testing was done 2 months
      after the war had begun and 18 months after the end of it. Psychiatric assessment
      was done at the same periods, and 30 months after the start of the study.
      RESULTS: After 2.5 years of follow-up, there were no signs of endocrine or
      psychiatric disorders in any of the subjects. After the war, Beck Inventory of
      Depression and Hamilton Anxiety Rating Scale scores were significantly reduced.
      Suppression of the HPA axis was present during the war but not after.
      CONCLUSIONS: Prolonged psychological stress is associated with a transient
      suppression of the HPA axis, manifested by low morning cortisol and reduced
      cortisol response to ACTH. The reduction of cortisol response is sufficient to
      cause false diagnosis of HPA insufficiency.

PMID- 14974928
TI  - Variants of uncoupling protein-2 gene and obesity: interaction with peroxisome
      proliferator-activated receptorgamma2.
AB  - OBJECTIVE: To analyse the association of the UCP2 gene, alone or in combination
      with the PPARgamma2 gene, with obesity. DESIGN: Cross-sectional, case-control
      study. STUDY POPULATION: From a working population of 4500 Italian Caucasian
      employees of the Italian telephone company participating in a firm-sponsored
      health screening programme, we selected all those with obesity [n = 122; body
      mass index (BMI) > or = 30 kg/m2]. For each case, three nonobese age- and sex
      matched individuals were selected as controls from the same population (n = 374).
      Included in the study were also 76 severely obese (BMI > or = 40 kg/m2) patients
      consecutively admitted to the obesity clinic of the department. Diabetic
      individuals were excluded. MEASUREMENTS: The -866G/A UCP2 and the Pro12Ala
      PPARgamma2 polymorphisms were determined on genomic DNA of the studied
      individuals. Several metabolic and anthropometric measures were also obtained,
      like plasma glucose, insulin, triglycerides, total cholesterol, high-density
      lipoprotein (HDL) cholesterol and BMI. RESULTS: BMI, plasma glucose, insulin,
      triglycerides, total and HDL cholesterol were not significantly different in
      carriers and noncarriers of the -866G/A variant. No significant association was
      observed between the -866G/A UCP2 gene polymorphism and moderate or severe
      obesity. This was also observed when the UCP2 polymorphism was analysed in
      combination with the PPARgamma2 polymorphisms. CONCLUSIONS: The -866G/A variants
      of the UCP2 gene are not associated with either obesity or other features of the
      metabolic syndrome in the studied groups of the Italian population. This negative
      finding is not modified after a combined analysis of the UCP2 polymorphism and
      the Pro12Ala polymorphism of PPARgamma2.

PMID- 14974929
TI  - 99mTc-SestaMIBI scintigraphy of thyroid gland in a patient with primary
      hyperparathyroidism: unusual features due to coesistence of a thyroid papillary
      carcinoma.

PMID- 14974930
TI  - Partial thyroxine-binding globulin (TBG) deficiency in a family with no
      detectable mutation of the TBG gene.

PMID- 14974931
TI  - Osteoporosis: Pathophysiology and Clinical Management.

PMID- 14974932
TI  - Genetics for Endocrinologists: The Molecular Genetic Basis of Endocrine
      Disorders.

PMID- 14974933
TI  - The malignant side of successful transplantation.

PMID- 14974934
TI  - Clarence Cook Little (1888-1971): the genetic basis of transplant immunology.

PMID- 14974935
TI  - Vital role of medical examiners and coroners in organ transplantation.
AB  - Many people die owing to the shortage of donor organs. Medical examiners and
      coroners (MEs/Cs) play a vital role in making organs available for potential
      recipients. Medical examiners'/coroners' case data were collected using a
      structured confirmatory-recorded methodology for calendar years 2000-01 and were
      linked and analyzed with donor and transplant data from the United Network for
      Organ Sharing, predicting the nature and extent of the loss of donor organs.
      Nearly seven percent of ME/C cases were denied recovery during 2000-01. Because
      353 and likely, 411 potential organ donors (PODs) were denied, as many as 1400
      persons on transplant waiting lists did not receive organs because of ME/C
      denials. Problematically for pediatric patients awaiting transplantation, nearly
      half of all ME/C denials occurred in pediatric patients. Eighteen percent of PODs
      aged five or less and 44.2% of child abuse PODs were denied recovery by the ME/C.
      There were no (zero) denials in three of the five largest U.S. cities and in four
      states. Since 1994, two states have enacted legislation restricting the
      circumstances of ME/C denials, resulting in an 83% decrease in ME/C denials.
      Release of all organs from ME/C cases is needed urgently to protect the lives of
      those persons awaiting transplantation. Medical examiners and coroners deserve
      recognition for their efforts in advocating methods and/or regulation/legislation
      designed to achieve 100% release of life-saving organs for transplantation.

PMID- 14974936
TI  - The role of viruses in cardiac allograft vasculopathy.
AB  - Considerable evidence suggests a role for viruses in transplant arteriosclerosis
      (TA), including observational data, experimental models and therapeutic trials
      implicating human cytomegalovirus (HCMV) in the progression to TA. In pediatric
      heart transplant patients, adenoviral genome in endomyocardial biopsies (EMB) is
      an important predictor of TA and graft loss. During CMV viremia, EMBs from adult
      patients demonstrate endothelialitis and vascular smooth muscle cell
      proliferation. These changes are predictors of subsequent diffuse TA. HCMV
      immediate early proteins (IE-1 and IE-2) increase the constitutive expression of
      intercellular adhesion molecule-1 (ICAM-1) independent of other intracellular
      cytokines. Likewise, viral chemokines such as US28 have been implicated in
      vascular disease because of their ability to induce smooth muscle cell migration.
      Recent data suggests that CMV might accelerate TA through its ability to abrogate
      the vascular protective effects of the endothelium-derived nitric oxide system
      (eNOS). Confirmation of causality requires clinical trials demonstrating that
      antiviral agents such as ganciclovir inhibit TA. Such studies in patients though
      limited to retrospective analyses, suggest that ganciclovir prophylaxis early
      after heart transplantation reduces the risk of TA. These observations emphasize
      the need for randomized controlled clinical trials to confirm a causal role for
      CMV (and other viruses) in TA.

PMID- 14974937
TI  - The consequences of public policy to buy and sell organs for transplantation.

PMID- 14974938
TI  - Endothelial cell protection by dextran sulfate: a novel strategy to prevent acute
      vascular rejection in xenotransplantation.
AB  - We showed recently that low molecular weight dextran sulfate (DXS) acts as an
      endothelial cell (EC) protectant and prevents human complement- and NK cell
      mediated cytotoxicity towards porcine cells in vitro. We therefore hypothesized
      that DXS, combined with cyclosporine A (CyA), could prevent acute vascular
      rejection (AVR) in the hamster-to-rat cardiac xenotransplantation model.
      Untreated, CyA-only, and DXS-only treated rats rejected their grafts within 4-5
      days. Of the hearts grafted into rats receiving DXS in combination with CyA, 28%
      survived more than 30 days. Deposition of anti-hamster antibodies and complement
      was detected in long-term surviving grafts. Combined with the expression of
      hemoxygenase 1 (HO-1) on graft EC, these results indicate that accommodation had
      occurred. Complement activity was normal in rat sera after DXS injection, and
      while systemic inhibition of the coagulation cascade was observed 1 h after DXS
      injection, it was absent after 24 h. Moreover, using a fluorescein-labeled DXS
      (DXS-Fluo) injected 1 day after surgery, we observed a specific binding of DXS
      Fluo to the xenograft endothelium. In conclusion, we show here that DXS + CyA
      induces long-term xenograft survival and we provide evidence that DXS might act
      as a local EC protectant also in vivo.

PMID- 14974939
TI  - Transplantation-induced functional/morphological changes in rat aorta allografts
      differ from those in arteries of rat kidney allografts.
AB  - The functional/morphological changes observed in rat aorta allografts were
      compared with those seen in the arteries of rat kidney allografts. Untreated
      allografts (F344-to-LEW) were collected at various times post-transplantation
      (Tx). Vascular smooth muscle cell (SMC) constriction to phenylephrine (Phe) and
      endothelial cell (EC)-dependent relaxation to acetylcholine (Ach) were assessed.
      Neointima formation in graft vessels was assessed by histology. In aorta
      allografts, the effects of Phe and Ach were irreversibly abolished within 3-2
      weeks post-Tx. Neointima formation was consistently detected between 4 and 8
      weeks post-Tx. In kidney allografts, sign of vasculopathy was seen in 10, 30 and
      40% of resistance arteries at 8, 16 and 33 weeks post-Tx, respectively. In the
      main renal artery, substantial neointima formation was not apparent before 33
      weeks post-Tx, the vasoconstrictor effect of Phe was fully maintained until then,
      and Ach-induced vasorelaxation was irreversibly reduced by approximately 70% from
      week 2 post-Tx onwards. These results indicate that the post-Tx
      functional/morphological changes seen in aorta allografts do not reflect those
      seen in arteries of kidney allografts. Hence, renal arteries from rat kidney
      allografts can be considered as a more relevant model to study the cascade of
      events leading to Tx-induced CGA in solid organ allografts.

PMID- 14974940
TI  - Linking inflammation to acute rejection in small-for-size liver allografts: the
      potential role of early macrophage activation.
AB  - This study aims to investigate the immunological status of small-for-size liver
      allografts and possible mechanism that contributes to the accelerated immune
      response in these allografts. Eight experimental groups were: whole isografts;
      40% isografts; whole allografts, no treatment; 40% allografts, no treatment;
      whole allografts with sodium salicylate intraperitoneal injection, D0-3; 40%
      allografts with sodium salicylate, D0-3; whole allografts with FK506
      intramuscular injection D0-3, and 40% allografts with FK506, D0-3. The 40%
      allografts survived significantly shorter than whole allografts (p=0.02). At 72 h
      after reperfusion, a higher number of macrophages infiltrated into the periportal
      area of small-for-size allografts than whole allografts. Remarkable up-regulation
      of interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-10 (IL-10) and
      interferon-gamma (IFN-gamma) messenger RNA (mRNA) levels were detected in small
      for-size allografts within 24 h after reperfusion. Sodium salicylate
      administration reduced IL-1beta and IFN-gamma mRNA in both small-for-size and
      whole allografts, but it could decrease IL-2 and IL-10 mRNA levels only in small
      for-size allografts. In vitro study revealed that CD80, CD86 and CD11b expression
      on macrophages was augmented after IL-1beta stimulation, whereas the up
      regulation could be blocked by sodium salicylate. In conclusion, early activation
      of macrophages as a result of graft injury might play an important role in the
      accelerated acute rejection process in small-for-size allografts.

PMID- 14974941
TI  - Brain death impairs pancreatic microcirculation.
AB  - Brain death (BD) influences the quality of donor grafts in transplantation. To
      evaluate the impact of BD on pancreas grafts, we investigated the influence of BD
      on the microcirculation and histology of the pancreas in a rat model of explosive
      BD. A group of Wistar rats (n=7), rendered brain dead by inflating an
      intracranially inserted Fogarty catheter was compared with controls (CO) using
      intravital epifluorescence-microscopy over 4 h after BD induction; functional
      capillary density (FCD), leukocyte adherence (AL) in post-capillary venules,
      histology and pancreatic enzymes were investigated. Four hours after BD, FCD
      decreased (333 +/- 11 vs. baseline 444 cm/cm2 +/- 5 SEM; p<0.01) and showed lower
      values than CO (388 +/- 9 p<0.01). In BD, AL was increased (628 cells/mm2 +/- 110
      SEM vs. baseline 123 +/- 32, and vs. CO 180 +/- 33; p<0.001). BD caused increased
      histological damage (CO 1.6 score-points +/- 0.7 SD vs. BD 8.3 +/- 7.1; p<0.05).
      Amylase was higher in BD (p<0.05) but did not reach pathological values. We show
      for the first time that BD causes relevant changes in pancreatic
      microcirculation, histology and leukocyte endothelial interaction which might
      have a serious impact on the function of grafts. New strategies for preventing
      this damage are therefore highly desirable in order to improve the outcome of
      pancreas transplantation.

PMID- 14974942
TI  - Payment for living donor (vendor) kidneys: a cost-effectiveness analysis.
AB  - The supply of kidneys does not meet the demand. As a consequence, the waiting
      time for a cadaver kidney continues to lengthen, and there is renewed debate
      about payment for living donors. To facilitate this debate, we studied what
      amount of payment would be cost-effective for society, i.e. what costs would be
      saved (if any) by removing a patient from the waiting list using a paid (living
      unrelated: LURD) donor-vendor. A Markov model was developed to calculate the
      expected average cost and outcome benefits of increasing the organ supply and
      reducing waiting times by adding paid LURD organs to the available pool. We found
      that a LURD transplant saved $94,579 (US dollars, 2002), and 3.5 quality-adjusted
      life years (QALYs) were gained. Adding the value of QALYs, a LURD transplant
      saved $269 319, assuming society values additional QALYs from transplantation at
      the rate paid per QALY while on dialysis. At a minimum, a vendor program would
      save society >$90,000 per transplant and provides QALYs for the ESRD population.
      Thus, society could break even while paying $90,000/kidney vendor.

PMID- 14974943
TI  - Lymphomas after solid organ transplantation: a collaborative transplant study
      report.
AB  - We used the Collaborative Transplant Study database to analyze the incidence,
      risk, and impact of malignant lymphomas in approximately 200,000 organ transplant
      recipients. Over a 10-year period, the risk in renal transplant recipients was
      11.8-fold higher than that in a matched nontransplanted population (p<0.0001).
      The majority of lymphomas were diagnosed after the first post-transplant year.
      Heart-lung transplants showed the highest relative risk (RR 239.5) among
      different types of organ transplants. In kidney recipients, immunosuppression
      with cyclosporine did not confer added risk compared with azathioprine/steroid
      treatment, whereas treatment with FK506 increased the risk approximately twofold.
      Induction therapy with OKT3 or ATG, but not with anti-IL2 receptor antibodies,
      increased the risk of lymphoma during the first year. Antirejection therapy with
      OKT3 or ATG also increased the risk. First-year mortality in renal and heart
      transplant patients with lymphoma was approximately 40% and 50%, respectively,
      and showed no improvement in recent years. A pattern of preferential localization
      to the vicinity of the transplant was noted, and the prognosis of the patient was
      related to localization. This study highlights the continuing risk for lymphoma
      with time post-transplantation, the contribution of immunosuppression to
      increased risk, and continuing poor outcomes in patients with post-transplant
      lymphoma.

PMID- 14974944
TI  - Enteric-coated mycophenolate sodium is therapeutically equivalent to
      mycophenolate mofetil in de novo renal transplant patients.
AB  - The introduction of mycophenolate mofetil (MMF) represented a major advance in
      transplant medicine, although optimal use may be limited by gastrointestinal (GI)
      side-effects. An enteric-coated formulation of mycophenolate sodium (EC-MPS;
      myfortic) has been developed with the aim of improving the upper GI tolerability
      of mycophenolic acid. Therapeutic equivalence of EC-MPS (720 mg b.i.d.) and MMF
      (1000 mg MMF b.i.d.), with concomitant cyclosporine microemulsion (Neoral) and
      corticosteroids, was assessed in 423 de novo kidney transplant patients recruited
      to a 12-month, double-blind study. Efficacy failure (biopsy-proven acute
      rejection [BPAR], graft loss, death or loss to follow up) at 6 months (EC-MPS
      25.8% vs. MMF 26.2%; 95% CI: [-8.7, +8.0]) demonstrated therapeutic equivalence.
      At 12 months, the incidence of BPAR, graft loss or death was 26.3% and 28.1%, and
      of BPAR alone was 22.5% and 24.3% for EC-MPS and MMF, respectively. Among those
      with BPAR, the incidence of severe acute rejection was 2.1% with EC-MPS and 9.8%
      with MMF (p=ns). The safety profile and incidence of GI adverse events were
      similar for both groups. Within 12 months, 15.0% of EC-MPS patients and 19.5% of
      MMF patients required dose changes for GI adverse events (p=ns). Enteric-coated
      MPS 720 mg b.i.d. is therapeutically equivalent to MMF 1000 mg b.i.d. with a
      comparable safety profile.

PMID- 14974945
TI  - Enteric-coated mycophenolate sodium can be safely administered in maintenance
      renal transplant patients: results of a 1-year study.
AB  - With the objective of enhancing upper gastrointestinal (GI) tolerability, enteric
      coated mycophenolate sodium (EC-MPS, myfortic, Novartis Pharma AG, Basel,
      Switzerland) has been developed. This double-blinded, 12-month study investigated
      whether renal transplant patients taking mycophenolate mofetil (MMF) can be
      safely converted to EC-MPS. Stable kidney transplant patients were randomized to
      receive EC-MPS (720 mg b.i.d.; n=159) or continue receiving MMF (1000 mg b.i.d.;
      n=163). The incidence of GI adverse events (AEs) was similar at 3 months (primary
      endpoint: EC-MPS 26.4%; MMF 20.9%; p=NS) and at 12 months (EC-MPS 29.6%; MMF
      24.5%; p=NS). The increase from baseline in mean GI AE severity score, adjusted
      for duration, tended to be lower in EC-MPS patients (3 months: 0.15 vs. 0.20; 12
      months: 0.23 vs. 0.47; p=NS). Neutropenia (<1500 cells/mm3) within the first 3
      months (coprimary endpoint) was low in both groups (EC-MPS 0.6%; MMF 3.1%; p=NS).
      Although the overall incidence of infections was similar, the number of serious
      infections was significantly lower in EC-MPS patients (8.8% vs. 16.0%; p<0.05).
      Similar rates of efficacy failure (EC-MPS 2.5%; MMF 6.1%; p=NS), biopsy-proven
      acute rejection (EC-MPS 1.3%; MMF 3.1%; p=NS) and biopsy-proven chronic rejection
      (EC-MPS 3.8%; MMF 4.9%; p=NS) were observed in both groups. In conclusion, renal
      maintenance patients can be converted from MMF to EC-MPS without compromising the
      safety and efficacy profile associated with MMF.

PMID- 14974946
TI  - Systolic blood pressure diurnal variation is not a predictor of renal target
      organ damage in kidney transplant recipients.
AB  - Elevated blood pressure and diurnal blood pressure variation detected by
      ambulatory blood pressure monitoring has been shown to be predictive of worse
      outcome in end-stage renal disease patients in small studies. What has been
      lacking is a large study to determine whether these ambulatory blood pressure
      monitoring (ABPM)-derived variables are predictors of worse outcome in renal
      transplant recipients. All the patients that underwent renal transplantation and
      follow up at this institution from January 1998 till October 2002 were involved
      in this study (n=177). All patients were followed up for at least 48 weeks. Last
      creatinine correlated positively with duration of dialysis (p=0.035, r=0.158),
      kidney-donor age (p<0.0001, r=0.377), early kidney function (p<0.0001, r=0.610,
      r=0.683), 24-h systolic blood pressure (SBP) load (p=0.002, r=0.228), and ABPM
      derived pulse pressure (p<0.0001, r=0.269). However neither office blood pressure
      nor SBP diurnal variation were predictors of kidney outcome. Regression analysis
      showed that early kidney function was the only independent predictor of
      transplant outcome (p<0.0001). Systolic blood pressure diurnal variation, though
      an important predictor of target organ damage in chronic kidney disease patients,
      was not a predictor of renal transplant function in renal transplant recipients.
      Only early kidney function was an independent predictor of later serum
      creatinine.

PMID- 14974947
TI  - Correlation of quantitative digital image analysis with the glomerular filtration
      rate in chronic allograft nephropathy.
AB  - Chronic allograft nephropathy (CAN) is characterized by progressive renal
      functional loss and histologic abnormalities of one or more tissue compartments.
      In this study, correlations between histologic abnormalities and graft function
      [glomerular filtration rate (GFR, measured by iothalamate clearance), serum
      creatinine (SCr) and urinary protein (UPr)] were investigated using biopsies from
      49 patients with newly diagnosed CAN. Extent of tubulointerstitial fibrosis
      (%TIF), as assessed by a semi-quantitative score, correlated significantly with
      GFR, SCr and UPr. The close correlation between %TIF and GFR suggested that
      quantitative measurement of %TIF may predict functional consequences of CAN.
      Calculation of %TIF by computerized digital analysis was performed using four
      strategies: (a) quantitation of blue material in Masson's trichrome (MT)-stained
      sections, (b) quantitation of red material in Sirius Red-stained sections (SR
      nonpolarized), (c) quantitation of birefringent material in Sirius Red stained
      sections examined under polarized light (SR-polarized) and (d) quantification of
      brown material in sections stained by immunoperoxidase for alpha-smooth muscle
      actin. Only the SR-nonpolarized score correlated significantly with GFR at the
      time of biopsy-diagnosis of CAN. We conclude that digital analysis strategies
      demonstrate variable accuracy in quantifying %TIF. Validation of the SR
      nonpolarized strategy against histologic scoring and GFR supports the application
      of this technique to longitudinal studies of CAN.

PMID- 14974948
TI  - Impact of donor spontaneous intracranial hemorrhage on outcome after heart
      transplantation.
AB  - Donor cause of death has been suggested to have a significant impact on cardiac
      transplant morbidity and mortality. Our objective was to evaluate the impact of
      donor spontaneous intracranial bleeding on clinical outcome after heart
      transplantation. A group of 160 recipients underwent cardiac transplantation from
      donors with spontaneous intracranial bleeding (ICB group). These were compared
      with 197 recipients who were transplanted from trauma donors (Trauma group). A
      higher 4-year mortality rate was noted in the ICB group (24% vs. 14%, p=0.015).
      ICB as a cause of donor death was an independent predictor of recipient mortality
      (adjusted hazard ratio 2.02, 95% CI 1.27-3.40, p<0.0001). Compared with the
      Trauma group, the ICB group had an increased incidence of post-transplant graft
      dysfunction during the first week of transplant (10% vs. 3%, p=0.007), and higher
      incidence of interstitial myocardial fibrosis on their endomyocardial biopsies
      within 4 weeks of transplant (21% vs. 9%, p=0.0012). There was a trend towards an
      increased rate of allograft vasculopathy in the ICB group (competing risks
      adjusted hazard ratio 1.39, 95% CI 0.90-2.13, p = 0.14).

PMID- 14974949
TI  - The burden of chronic kidney disease in renal transplant recipients.
AB  - The National Kidney Foundation has developed guidelines for the diagnosis and
      classification of chronic kidney disease (CKD) but it is not known whether these
      are applicable to renal transplant recipients. This study determined the
      prevalence of CKD according to the stages defined in the guidelines, the
      complications related to CKD and whether the prevalence of complications was
      related to CKD stage in 459 renal transplant recipients. CKD was present in 412
      patients (90%) and 60% were in CKD Stage 3 with a glomerular filtration rate
      (GFR) between 30 and 59 mL/min/1.73 m2. The prevalence of anemia increased from
      0% in Stage 1 to 33% in Stage 5 (p<0.001). Hypertension was present in 86% and
      increased from 60% in Stage 1 to 100% in Stage 5 (p=0.02). The number of anti
      hypertensives per patient increased from 0.7 in Stage 1 to 2.3 in Stage 5
      (p<0.001). The number of CKD complications per patient increased from 1.1 in
      Stage 1 to 2.7 in Stage 5 (p<0.001). We conclude that CKD and the complications
      of CKD are highly prevalent in renal transplant recipients. The classification of
      renal transplant patients by CKD stage may help clinicians identify patients at
      increased risk and target appropriate therapy to improve outcomes.

PMID- 14974950
TI  - Complement factor H deficiency in acute allograft glomerulopathy and post
      transplant hemolytic uremic syndrome.
AB  - Acute allograft glomerulopathy (AAG) is a distinct form of allograft rejection
      characterized by cytotoxic T-cell-mediated injury to the renal glomerular and
      arteriolar endothelium. Acute allograft glomerulopathy is characterized by
      mononuclear cell infiltration of glomerular capillary tufts in association with
      endothelial cell hypertrophy and injury. Intra-glomerular thrombi have been
      described in AAG, suggesting that overlapping features of AAG and post-transplant
      thrombotic microangiopathy (TMA) may coexist. We present a case suggesting that
      complement factor H deficiency, a known hereditary risk factor for TMA, may also
      favor development of AAG. We discuss the potential implications of factor H
      deficiency in the pathophysiology of renal allograft microvascular injury,
      leukocyte infiltration and formation of intraglomerular platelet thrombi. We
      propose that unopposed complement activation is a risk factor for both immune and
      nonimmune forms of microvascular injuries in renal allografts.

PMID- 14974951
TI  - Recovery from pure red cell aplasia caused by anti-erythropoietin antibodies
      after kidney transplantation.
AB  - The use of recombinant human erythropoietin (rHuEPO) is a major advance in the
      treatment of patients with anemia caused by chronic renal failure (CRF). The
      development of antierythropoietin (anti-EPO) antibodies following treatment with
      rHuEPO has been observed in an increasing number of patients. This causes pure
      red cell aplasia (PRCA) and requires the definitive withdrawal of rHuEPO. Many
      patients require immunosuppressive therapy before anti-EPO antibodies disappear
      completely. We report a case of PRCA owing to anti-EPO in a 20-year-old
      hemodialyzed man who was receiving immunosuppressive therapy for a liver
      transplantation carried out in childhood. He required repeated red cell
      transfusions until a kidney transplantation was performed. He received an
      induction therapy with antithymocyte globulins and a maintenance regimen
      consisting of steroids, tacrolimus and mycophenolate mofetil. This new
      immunosuppressive treatment led to the complete disappearance of anti-EPO
      antibodies within a few weeks after the kidney transplantation. Erythropoiesis
      and endogenous erythropoietin synthesis were restored following transplantation,
      without leading to an increase in the titer of anti-EPO antibodies.

PMID- 14974952
TI  - Unresectable squamous cell carcinoma of donor origin treated with
      immunosuppression withdrawal and liver retransplantation.
AB  - Posttransplantation allograft malignancy of donor origin is a rare complication
      after liver transplantation. In the case described, subjective fevers and
      nonspecific abdominal complaints nearly 6 months following cadaveric liver
      transplantation in a young woman prompted an evaluation which was remarkable for
      a large central liver mass. A poorly differentiated squamous cell carcinoma was
      diagnosed, but was unresectable at exploration. The tumor was confined to the
      liver. Histocompatibility testing using polymerase chain reaction (PCR)
      amplification techniques identified both donor and recipient HLA alleles. The
      patient was treated with chemoembolization, systemic chemotherapy and cessation
      of immunosuppression. Repeat biopsy 2 months later showed the tumor to be
      completely necrotic. With decompensated liver disease, she was relisted and
      retransplanted. More than 2 years later she remains disease-free with complete
      pathological remission. This is the only reported case of squamous cell carcinoma
      of donor origin arising in a transplanted liver.

PMID- 14974953
TI  - Human renal allograft rejection despite the absence of allogeneic passenger
      leukocytes.
AB  - Passenger leukocytes have been suggested to be both pro-tolerant and immunogenic.
      The opportunity to evaluate the role of allogeneic passenger leukocytes in humans
      was presented by a 47-year-old man who donated bone marrow to his HLA-identical
      leukemic sister. Eleven years later he developed renal failure. The sister's
      marrow was noted to be 100% XY karyotype and free of malignancy. She donated a
      kidney to her brother. Immunosuppression was tapered following transplantation.
      After 6 months, the recipient was on monotherapy sirolimus, 1 mg every third day.
      A surveillance biopsy was normal and sirolimus was stopped. Eight weeks later, he
      presented with severe rejection that reversed with Thymoglobulin. Renal function
      returned to baseline and has been stable on conventional immunosuppression.

PMID- 14974954
TI  - First report of cryopreserved human hepatocytes based bioartificial liver
      successfully used as a bridge to liver transplantation.
AB  - Cryopreserved human hepatocytes could be the best type of cells to be used in a
      bioartificial liver (BAL) device due to reduced biosafety and biocompatibility
      risks. Banking of primary human hepatocytes, obtained from livers unwanted for
      transplantation at harvesting, could be used as a source of human liver cells for
      BAL treatment. We describe herein for the first time the case of a patient
      affected by fulminant hepatic failure (FHF) due to acute HBV infection that was
      successfully bridged to emergency liver transplantation by BAL treatment using
      cryopreserved primary human hepatocytes. The use of cryopreserved primary human
      hepatocytes as the biological part of the BAL device has never been described
      before and might be considered as a possible alternative to xenogenic material or
      human tumoral cell lines due to reduced biosafety and biocompatibility risks.

PMID- 14974955
TI  - Hepatic artery and post-transplantation hemodynamics and function.

PMID- 14974957
TI  - The time for a grand challenge in wound healing is at hand.

PMID- 14974958
TI  - Advances in the treatment of the diabetic foot: Is there a role for adjunctive
      hyperbaric oxygen therapy?
AB  - There have been many advances in the treatment of wounds made in the last decade.
      Innovative techniques of wound closure, topical agents, aggressive vascular
      repair, focused wound care management, and adjunctive hyperbaric oxygen therapy
      are but a few of these improvements. The vital role of oxygen in wound healing is
      becoming better understood, in no small part, due to Dr. T. K. Hunt and his
      colleagues at the Wound Healing Laboratory at the University of California, San
      Francisco. Elements of that contribution will be examined in this article. How
      these elements may be applied to improve wound healing will be explained and the
      possible role of adjunctive hyperbaric oxygen therapy based on sound science in
      the management of the difficult diabetic foot wound, will be highlighted.

PMID- 14974959
TI  - Bacterial load in relation to vacuum-assisted closure wound therapy: a
      prospective randomized trial.
AB  - Vacuum-assisted closure has become a new technique in the challenging management
      of contaminated, acute, and chronic wounds. Although promising clinical results
      have been described, scientific proof to substantiate the mechanism of action of
      this therapy is scarce. In the present study, we examined whether the positive
      effect on wound healing found in vacuum-assisted closure-treated wounds could be
      explained by an effect on the bacterial load. Fifty-four patients who needed open
      wound management before surgical closure were included in this study. Wounds were
      randomized to either vacuum-assisted closure therapy (n= 29) or treatment by
      conventional moist gauze therapy (n= 25). Healing was characterized by
      development of a clean granulating wound bed ("ready for surgical therapy") and
      reduction of wound surface area. To quantify bacterial load, biopsies were
      collected. No significant difference was found in time needed to reach "ready for
      surgical therapy" comparing both therapies. Wound surface area reduction was
      significantly larger in vacuum-assisted closure-treated wounds: 3.8 +/- 0.5
      percent/day (mean +/- SEM) compared to conventional-treated wounds (1.7 +/- 0.6
      percent/day; p < 0.05). The total quantitative bacterial load was generally
      stable in both therapies. However, nonfermentative gram negative bacilli showed a
      significant decrease in vacuum-assisted closure-treated wounds (p < 0.05),
      whereas Staphylococcus aureus showed a significant increase in vacuum-assisted
      closure-treated wounds (p < 0.05). In conclusion, this study shows a positive
      effect of vacuum-assisted closure therapy on wound healing, expressed as a
      significant reduction of wound surface area. However, this could not be explained
      by a significant quantitative reduction of the bacterial load.

PMID- 14974960
TI  - Role of "fibrin" cuffs in chronic nonspecific oral ulceration.
AB  - We report the novel finding of matrix-rich "fibrin" cuffs in chronic nonspecific
      oral ulceration and propose a possible role for these lesions. Pericapillary
      cuffs are typically found in chronic venous ulceration. Vascular cuffs, which
      form in the base and margins of leg ulcers, have been reported to contain fibrin,
      laminin, fibronectin, tenascin, and types I and III collagen. Histologically
      identical vascular cuffs are present in oral ulcers of unusually prolonged
      chronicity and their occurrence in the oral cavity suggests that chronic venous
      insufficiency and back pressure are not essential to their formation. It is
      proposed that the matrix-rich pericapillary cuffs may act as a scaffold for
      angiogenesis in ulceration of prolonged duration.

PMID- 14974961
TI  - Effects of a CDK inhibitor on lens regeneration.
AB  - Lens regeneration in adult newts is always initiated from the dorsal iris by
      transdifferentiation of the pigment epithelial cells. One of the most important
      early events should be the ability of pigment epithelial cells to dedifferentiate
      and re-enter the cell cycle. As a first step in an attempt to study this event,
      we have decided to examine the effects of a cyclin-dependent kinase-2 inhibitor
      on lens regeneration. At the appropriate concentration, this inhibitor completely
      abolished the ability of pigment epithelial cells to form a new lens, but it did
      not stop them from dedifferentiating and forming a small lens vesicle. The
      effects of this inhibitor seem to be mediated by its opposite effects on cell
      proliferation and apoptosis. The inhibitor significantly reduced cell
      proliferation and enhanced apoptosis of pigment epithelial cells both in vitro
      and in vivo and of the regenerating lens in vivo.

PMID- 14974962
TI  - Transplantation of the urinary bladder and other organs in the subcutaneous
      tissue induces cyst formation and epithelialization: its potential usefulness in
      regenerative medicine.
AB  - Certain hollow organs are known to form cysts when heterologously transplanted.
      In order to examine the usefulness of the phenomenon for regenerative medicine,
      rat urinary bladders and other organs were allo-transplanted under the
      subcutaneous tissue of the back. These transplanted tissues very often formed
      cysts covered with epithelia. The epithelia covered an area about twice the
      original size. In the case of the urinary bladder, the epithelium started moving
      from the edge of the transplants around day 3 after the operation, and as time
      proceeded, the tela submucosa and tunica muscularis also moved to encircle the
      epithelium, and formed the wall of the cyst. The basal laminae were formed under
      the newly expanded epithelium slightly behind the leading tip. All of the organs
      tested had the capability of cyst formation and epithelialization, although their
      rate differed between organs. The results are discussed with reference to the
      potential use of cyst formation for regenerating damaged organs.

PMID- 14974963
TI  - Effect of cytokine growth factors on the prevention of acute wound failure.
AB  - Cytokine growth factor treatment of chronic wounds has met with mixed results.
      The chronic wound presents a hostile environment to peptides such as growth
      factors. Cytokine growth factors have not been studied extensively in acute
      wounds. However, incisional hernias are a major example of acute wound failure
      that has not been solved by various mechanical approaches. A biological approach
      to acute wound failure by use of cytokine growth factors may offer a new
      strategy. A rodent incisional hernia model was used. Seventy-six rats underwent 3
      cm midline celiotomies and were closed with fine, fast-absorbing sutures to
      induce intentional acute wound failure. Group 1 received no other treatment. The
      midline fascia in Groups 2-10 was infiltrated with 100 microl of vehicle alone or
      vehicle containing various test cytokine growth factors. Necropsy was performed
      on postoperative day 28 and the wounds were examined for herniation. Incisional
      hernias developed in 83 percent (13/16) of untreated incisional and 88 percent
      (7/8) and 83 percent (5/6) of the two vehicle-treated incisions (PBS and
      carboxymethylcellulose). Hernia incidences were decreased by priming of the
      fascial incision with transforming growth factor-beta(2) (12%, 1/8), basic
      fibroblast growth factor (25%, 2/8) and interleukin-1 beta (50%, 3/6) (p < 0.05).
      Aqueous platelet-derived growth factor, becaplermin, insulin-like growth factor,
      and granulocyte macrophage-colony stimulating factor did not significantly
      decrease the incidence of acute wound failure (p > 0.05). A biological approach
      to acute wound failure as measured by incisional hernia formation can be useful
      in reducing the incidence of this complication. Transforming growth factor
      beta(2), basic fibroblast growth factor, and interleukin 1 beta all eliminated or
      significantly reduced the development of incisional hernias in the rat model.

PMID- 14974964
TI  - Nerve growth factor accelerates wound healing in diabetic mice.
AB  - Patients with diabetic neuropathy have reduced numbers of cutaneous nerves, which
      may contribute to an increased incidence of nonhealing wounds. Nerve growth
      factor (NGF) has been reported to augment wound closure. We hypothesized that
      topical 2.5S NGF, a biologically active subunit of the NGF polymer, would
      accelerate wound repair, augment nerve regeneration, and increase inflammation in
      excisional wounds in diabetic mice. A full-thickness 6-mm punch biopsy wound was
      created on the dorsum of C57BL/6J-m+ Leprdb mice (db/db) and heterozygous (db/-)
      littermates and treated daily with normal saline or 2.5S NGF (1 microg/day or 10
      microg/day) on post-injury days 0-6. Time to closure, wound epithelialization,
      and degree of inflammation were compared using a Student's t-test. Color
      subtractive-computer-assisted image analysis was used to quantify immunolocalized
      nerves in wounds. Non-overlapping (20x) digital images of the wound were analyzed
      for nerve profile counts, area density (number of protein gene product 9.5
      positive profiles per unit dermal area) and area fraction (protein gene product
      9.5 positive area per unit dermal area). Healing times in db/db mice decreased
      from 30 days in normal saline-treated mice to 26 days in mice treated with 1
      microg/day NGF (p<0.05) and 24 days in mice treated with 10 microg/day NGF
      (p<0.02). A similar trend in db/- mice was not significant. NGF treatment
      augmented epithelialization in the db/db mice (p<0.05). Histological evaluation
      of inflammation in healed wounds showed no statistical difference between
      treatment groups. Total nerve number, area density, and area fraction were
      increased in NGF-treated wounds at 14, 21, and 35 days (p<0.05). The 2.5 NGF
      subunit may improve wound closure kinetics by promoting epithelialization and
      nerve regeneration. Further studies to determine the role of nerves in wound
      repair are warranted.

PMID- 14974965
TI  - TGF beta-like regulation of matrix metalloproteinases by anti-transforming growth
      factor-beta, and anti-transforming growth factor-beta 1 antibodies in dermal
      fibroblasts: Implications for wound healing.
AB  - Transforming growth factor beta (TGF-beta) stimulates collagen and matrix
      metalloproteinase-2 expression and inhibits MMP-1 expression in dermal
      fibroblasts. Anti-TGF-beta antibodies have been proposed in the prevention of
      wound scars. The goal of this research was to investigate the regulation of
      matrix metalloproteinases-1 and -2 expression at the protein, mRNA, and
      transcriptional levels using an anti-TGF-beta antibody to TGF-beta 1, 2, 3, and 5
      (all isoforms), and specifically by an anti-TGF-beta 1 antibody. Both antibodies,
      though at doses lower than the recommended neutralization dose, stimulated the
      expression of TGF-beta, and exhibited TGF-beta-like regulation of the matrix
      metalloproteinases. The antibodies inhibited matrix metalloproteinase-1 protein,
      mRNA, and promoter activity. The protein levels of matrix metalloproteinase-2
      were up-regulated to a greater extent than the matrix metalloproteinase-2 mRNA
      level by both antibodies. These effects of anti-TGF-beta and anti-TGF-beta 1
      antibodies on matrix metalloproteinase regulation were mimicked by exogenous TGF
      beta 1 but not rabbit or chicken IgG. We infer that the anti-TGF-beta1 isoform
      that forms part of the composition of the anti-TGF-beta antibody to all isoforms
      may be responsible for the feedback stimulation of TGF-beta and the resultant
      alterations in the expression of the matrix metalloproteinases by the anti-TGF
      beta antibodies.

PMID- 14974966
TI  - Down-regulation of connective tissue growth factor and type I collagen mRNA
      expression by connective tissue growth factor antisense oligonucleotide during
      experimental liver fibrosis.
AB  - Transforming growth factor (TGF)-beta 1 is a major mediator of liver fibrosis.
      Connective tissue growth factor (CTGF) mediates TGF-beta 1 pro-fibrogenic effects
      in vitro, but its in vivo role is unknown. Both TGF-beta 1 and CTGF are
      overexpressed in hepatic stellate cells during liver fibrosis. We have used
      antisense oligonucleotides to examine the role of CTGF in carbon tetrachloride
      induced liver fibrosis in mice. Mice received carbon tetrachloride together with
      CTGF or TGF-beta 1 antisense oligonucleotides for 2 weeks (preventive model), or
      carbon tetrachloride for 2 weeks followed by carbon tetrachloride and
      oligonucleotides for 2 more weeks (curative model). In both models, CTGF and TGF
      beta 1 oligonucleotides decreased by more than 50 percent the mRNA expression of
      their targets. Type I collagen mRNA was also decreased by about 40 percent in the
      preventive experiment. Tissue inhibitor of matrix metalloproteinase-1 mRNA
      expression and fibrotic deposition evaluated by Sirius red staining were not
      modified in any group. In summary, our results suggest that hepatic stellate
      cells can be targeted in vivo with oligonucleotides, and that reducing CTGF
      levels can lead to a decrease in fibrogenesis as shown by the reduction in type I
      collagen expression. The lack of effect on fibrosis may be due to the persistence
      of high tissue inhibitor of matrix metalloproteinase-1 expression.

PMID- 14974967
TI  - Combined administration of basic fibroblast growth factor protein and the
      hepatocyte growth factor gene enhances the regeneration of dermis in acute
      incisional wounds.
AB  - Hepatocyte growth factor (HGF) is a ligand for the c-Met receptor tyrosine
      kinase. This study was aimed to characterize the role of the HGF gene combined
      with basic fibroblast growth factor (bFGF) protein in wound healing by
      administering both of them locally to acute incisional skin wounds created on the
      backs of rats. The bFGF protein and the HGF gene were administered intradermally
      after incisional surgery. Apoptotic cells in wound lesions were identified by the
      terminal deoxynucleotide transferase-mediated nick-end labeling method, as well
      as by immunological detection of active caspase-3. While there was almost
      complete suppression of apoptosis with well-organized wound healing in animals
      treated with the HGF gene, the combination of bFGF protein and the HGF gene
      paradoxically resulted in less scarring along with the promotion of apoptosis.
      Histopathological examination revealed that scar formation was least apparent in
      rats treated with both bFGF and the HGF gene compared with controls or those
      treated with the bFGF or the HGF gene alone. It is thought that the combined
      administration of bFGF and the HGF gene immediately after skin incision may make
      the healing process occur closer to tissue regeneration through the induction of
      apoptosis, which occurred 1 week after surgery. HGF supplementation through gene
      therapy combined with bFGF protein may be an effective strategy for treating
      wounds, as it increases the apparent regeneration of the dermis to allow for
      "scarless wound healing."

PMID- 14974968
TI  - Liposome-mediated transfer of vascular endothelial growth factor cDNA augments
      survival of random-pattern skin flaps in the rat.
AB  - Tissue engineering is an application for gene therapy that is in its infancy. We
      show that simple liposomal-mediated gene transfer could result in a potentially
      useful biological effect in the field of wound healing. cDNA encoding the 165
      amino acid form of vascular endothelial growth factor complexed to commercially
      available liposomes was injected into rat skin 1 week before raising a random
      pattern 3 x 10 cm flap. The flap survival was enhanced by 14 percent, and was
      accomplished without accessing the arterial inflow of the territory. These
      results were statistically significant (p<0.002) and reproducible. No adverse
      effects were seen. Histological analysis of the angiogenesis localized much of
      the new vessel formation to the area around the hair follicles. Polymerase chain
      reaction amplification of extracted flap tissue confirmed the presence of the
      transgene.

PMID- 14974969
TI  - The JCR:LA-cp rat: a novel model for impaired wound healing.
AB  - JCR:LA-cp/cp obese rats and their lean controls were evaluated as a type 2
      diabetic wound healing model and the healing quality was characterized. This
      model of insulin resistance has been used extensively to study atherosclerosis
      but has not previously been used to study wound healing. Six circular excisional
      wounds were made on the dorsum of each rat and followed to day 21. Tracings of
      the wounds were made and used to assess the rate of wound closure. Planimetry
      showed a significantly diminished contraction of wounds in obese rats, but no
      significant difference in reepithelialization was observed. Collagen content was
      determined from the hydroxyproline content in wounded and unwounded skin. There
      were significantly lower levels of hydroxyproline in the wounds of obese compared
      to lean animals at day 21. Histology showed adipose tissue in place of dermal
      tissue in the JCR:LA-cp/cp rat in both unwounded tissue and in the wound at day
      21. Active transforming growth factor-beta 1 (TGF-beta 1) was measured in the
      serum using the plasminogen activator inhibitor-1/luciferase assay and serum
      total TGF-beta was measured using an enzyme-linked immunosorbent assay. Active
      TGF-beta was significantly higher in the serum of obese animals compared with
      lean animals, while total TGF-beta 1 was not significantly different between the
      groups. Both active and total TGF-beta was measured in tissue sections using the
      plasminogen activator inhibitor-1/luciferase assay. There was no significant
      difference in active TGF-beta between genotypes, while obese rats had
      significantly higher levels of total TGF-beta at day 21. These results indicate a
      deficiency in wound healing in obese animals characterized by decreased wound
      contraction, decreased collagen production, and changes in histology. The JCR:LA
      cp rat develops insulin resistance, atherosclerosis and early type 2 diabetes and
      may be a good model for impairment of wound healing in humans with metabolic
      syndrome.

PMID- 14974970
TI  - Lansoprazole promotes gastric mucosal cell proliferation and migration by
      activating p44/p42 mitogen-activated protein kinase.
AB  - Cell proliferation and migration are important repair mechanisms in cell defect
      type mucosal injuries, such as peptic ulcers. To evaluate the level of cell
      restitution in vitro, we established a normalized assay system for analyzing the
      area of a tissue defect created in the center of a cultured cell layer. Although
      proton pump inhibitors are known to be potently effective in the treatment of
      peptic ulcers by inducing acid suppression, they are also effective in low-acid
      conditions, such as in gastric ulcers associated with severe atrophic gastritis
      of the corpus. The present study was designed to examine the pH-independent
      effect of lansoprazole (LPZ) on cell restitution in vitro. The mouse gastric
      mucosal cell line, GSM06, was cultured to confluence. A 4-fluoric ethylene-tipped
      aluminum stick was then used to produce a cell-free area in the center of the
      culture well. After measuring the area of the cell defect using a digital
      analyzer equipped with an inverted microscope, LPZ was added to each well; the
      area of the residual cell defect was then measured 6 and 24 hours after LPZ
      administration. To investigate the involvement of the p44/p42 mitogen-activated
      protein kinase (MAPK) and p38 MAPK in this process, PD98059 (a MEK inhibitor) or
      FR167653 (a p38 MAPK inhibitor) was added to the cell cultures. In a separate
      experiment, GSM06 cells were cultured to the subconfluent level, each test agent
      was added, and the cell number in each well was measured using an MTT assay 16
      hours after the administration of the agents. Six hours after the addition of
      LPZ, a slight but significant increase in the cell restitution rate was observed
      in the LPZ-treated groups compared with that in the control group. After 24
      hours, a further significant increase in the cell restitution rate was observed
      in the LPZ groups compared with that in the control group. While the addition of
      PD98059 significantly attenuated the cell restitution rate in the LPZ groups, the
      addition of FR167653 had no such effect. The total cell number in the
      subconfluent cell cultures was significantly increased in the LPZ-treated groups
      compared with that in the control group. In conclusion, LPZ promotes the healing
      of injured gastric mucosal cells following injury by enhancing cell proliferation
      and migration. Furthermore, the mechanism by which cell proliferation and
      migration is promoted by LPZ may involve the activation of p44/p42 MAPK.

PMID- 14974971
TI  - Effects of a topical enamel matrix derivative on skin wound healing.
AB  - Enamel matrix derivative, obtained from developing porcine teeth, is composed
      mainly of amelogenin proteins and used topically in periodontal surgery for
      advanced periodontitis to regenerate lost connective tissues. The primary
      objective of this study was to investigate the effects of enamel matrix
      derivative on skin wound healing. Secondly, in vitro effects of enamel matrix
      derivative on dermal fibroblasts and microvascular endothelial cells were
      examined. Full-thickness, circular 2-cm skin wounds in white 16-week-old rabbits
      were treated thrice weekly with enamel matrix derivative (30 mg/ml) in the
      vehicle propylene glycol alginate or with vehicle alone. Enamel matrix derivative
      treatment increased the amount of granulation tissue and accelerated time to
      complete epithelialization by 3 days (p < 0.001) compared to vehicle treatment.
      In cultured fibroblasts, vascular endothelial growth factor levels in conditioned
      media were increased more than fivefold (p < 0.001) with enamel matrix derivative
      treatment (0.1mg/ml) over control, measured by specific enzyme-linked
      immunosorbent assay. Enamel matrix derivative also increased release of matrix
      metalloproteinase-2 more than threefold from fibroblasts (p < 0.001) and from
      endothelial cells (p < 0.001). Thus, enamel matrix derivative significantly
      accelerated wound closure in rabbits, possibly by increasing levels of growth
      factors and proteinases important for granulation tissue formation and
      remodeling.

PMID- 14974972
TI  - The early influence of albumin administration on protein metabolism and wound
      healing in burned rats.
AB  - Hypoalbuminemia is often claimed to impair wound healing, and therefore albumin
      has traditionally been administered to derive beneficial effects on general
      physiologic conditions including the nutritional state. However, the influence of
      albumin administration on systemic protein metabolism and wound healing is still
      unclear. Therefore, the objective of this study was to investigate the influence
      of albumin administration on protein metabolism and wound healing in burned rats.
      After receiving basic total parenteral nutrition (TPN) for 4 days, Sprague-Dawley
      rats underwent a 6-cm skin incision in the back and a burn involving 20 percent
      of the whole body surface. The rats were divided into three groups. Group I
      continued to receive basic TPN. Group II was given basic TPN, but 20 percent of
      the total nitrogen was replaced by albumin. Group III was administered basic TPN
      plus albumin equivalent to 20 percent of the total nitrogen of basic TPN. Group
      IV had the skin incision but no burn, receiving only basic TPN. All the groups
      were euthanized 4 days after the burn or skin incision. The wound healing
      potential in terms of tensile strength was enhanced by replacement and addition
      of albumin (groups II and III, respectively) after a 20 percent burn.
      Hydroxyproline levels in the wound tended to increase in group II, and
      significantly increased in group III. Whereas albumin replacement (group II) did
      not remarkably change the protein metabolism, albumin addition (group III)
      significantly increased both protein synthesis (S) and breakdown (B) with the S/B
      ratio and nitrogen balance remaining the same as with albumin-free nutrition
      (group I). The urinary 3-methyl-histidine/creatinine ratio significantly
      increased after burn in group III. We conclude that intravenous albumin
      administration enhanced incisional wound healing in burned rats. Increased
      protein synthesis with concurrent myolysis and protein breakdown by albumin
      addition (group III) was observed during wound healing.

PMID- 14974973
TI  - WOCN releases new clinical guideline.

PMID- 14975035
TI  - Unprecedented heat-related deaths during the 2003 heat wave in Paris:
      consequences on emergency departments.
AB  - In August 2003, France sustained an unprecedented heat wave that resulted in
      14,800 excess deaths. The consequences were maximal in the Paris area. The
      Assistance Publique-Hopitaux de Paris reported more than 2600 excess emergency
      department visits, 1900 excess hospital admissions, and 475 excess deaths despite
      a rapid organization. Indeed, simple preventice measures before hospital
      admissions are only able to reduce mortality which mostly occurred at home and in
      nursing homes.

PMID- 14975036
TI  - Prehospital advanced trauma life support: how should we manage the airway, and
      who should do it?
AB  - Adequate oxygenation at all times is of paramount importance to the critically
      injured patient to avoid secondary damage. The role of endotracheal intubation in
      out-of-hospital advanced trauma life support, however, remains controversial.
      Initiated by a recent observational study, this commentary discusses risks and
      benefits associated with prehospital intubation, the required personnel and
      training, and ethical implications. Recent evidence suggests that comprehensive
      ventilatory care already initiated in the field and maintained during transport
      may require the presence of a physician or another adequately skilled person at
      the scene. Benefits of such as service need to be balanced against increased
      costs.

PMID- 14975037
TI  - Recently published papers: all the usual suspects and carbon dioxide.

PMID- 14975038
TI  - Expanding intensive care medicine beyond the intensive care unit.
AB  - Intensive care medicine probably requires the artificial boundaries of an
      intensive care unit to nurture and legitimize the specialty. The next major step
      in intensive care medicine is to explore ways of optimizing the outcome of
      seriously ill patients by recognizing and resuscitating them at an earlier stage.
      Some of these ways include better education of existing staff; earlier
      consultation; and automatic calling by intensive care staff to abnormalities
      identifying at-risk patients. Some of these interventions are currently being
      evaluated and results should soon indicate their relative effectiveness.

PMID- 14975039
TI  - Time-dependent interventions.
AB  - The contribution by Pepe and colleagues provides additional evidence that initial
      defibrillation is not necessarily the optimal intervention for victims of cardiac
      arrest and especially when cardiac arrest has been untreated for more than 3 min.
      Precordial compression therefore remains the mainstay of basic life support
      cardiopulmonary resuscitation after sudden death. It is increasingly apparent
      that neither epinephrine whether in conventional or high doses nor vasopressin
      improve ultimate survival. To the contrary, there is evidence favoring beta1
      adrenergic blockade.

PMID- 14975040
TI  - Remifentanil for analgesia-based sedation in the intensive care unit.
AB  - Providing effective analgesia and adequate sedation is a generally accepted goal
      of intensive care medicine. Due to its rapid, organ independent and predictable
      metabolism the short acting opioid remifentanil might be particularly useful for
      analgesia-based sedation in the intensive care unit (ICU). This hypothesis was
      tested by two studies in this issue of Critical Care. The study by Breen et al.
      shows that remifentanil does not exert prolonged clinical effects when
      continuously infused in renal failure patients, although the weak acting
      metabolite remifentanil acid accumulates. The study by Muellejans et al. reports
      a multicenter trial comparing a remifentanil versus a fentanyl based regimen in
      ICU patients. With both substances a target analgesia and sedation level was
      reached, and no major differences were found when frequent assessments of the
      sedation level and according readjustments of doses were performed. These results
      are in accordance with other studies suggesting that the adherence to a clear
      analgesia-based sedation protocol might be more important then the choice of
      medications itself.

PMID- 14975041
TI  - Science Review: Vasopressin and the cardiovascular system part 2 - clinical
      physiology.
AB  - Vasopressin is emerging as a rational therapy for vasodilatory shock states. In
      part 1 of the review we discussed the structure and function of the various
      vasopressin receptors. In part 2 we discuss vascular smooth muscle contraction
      pathways with an emphasis on the effects of vasopressin on ATP-sensitive K+
      channels, nitric oxide pathways, and interaction with adrenergic agents. We
      explore the complex and contradictory studies of vasopressin on cardiac inotropy
      and coronary vascular tone. Finally, we summarize the clinical studies of
      vasopressin in shock states, which to date have been relatively small and have
      focused on physiologic outcomes. Because of potential adverse effects of
      vasopressin, clinical use of vasopressin in vasodilatory shock should await a
      randomized controlled trial of the effect of vasopressin's effect on outcomes
      such as organ failure and mortality.

PMID- 14975043
TI  - Clinical review: Outreach - a strategy for improving the care of the acutely ill
      hospitalized patient.
AB  - We examined the literature relating to the safe care of acutely ill hospitalized
      patients, and found that there are substantial opportunities for improvement.
      Recent research suggests substantial benefit may be obtained by systems of
      outreach care that facilitate better integration, co-ordination, collaboration
      and continuity of multidisciplinary care. Herein we review the various approaches
      that are being adopted, and suggest the need for continuing evaluation of these
      systems as they are introduced into different health care systems.

PMID- 14975042
TI  - Bench-to-bedside review: beta2-Agonists and the acute respiratory distress
      syndrome.
AB  - The acute respiratory distress syndrome (ARDS) is a devastating constellation of
      clinical, radiological and pathological signs characterized by failure of gas
      exchange and refractory hypoxia. Despite nearly 30 years of research, no specific
      pharmacological therapy has yet proven to be efficacious in manipulating the
      pathophysiological processes that underlie this condition. Several in vitro and
      in vivo animal or human studies suggest a potential role for beta2-agonists in
      the treatment of ARDS. These agents have been shown to reduce pulmonary
      neutrophil sequestration and activation, accelerate alveolar fluid clearance,
      enhance surfactant secretion, and modulate the inflammatory and coagulation
      cascades. They are also used widely in clinical practice and are well tolerated
      in critically ill patients. The present review examines the evidence supporting a
      role for beta2-agonists as a specific pharmacological intervention in patients
      with ARDS.

PMID- 14975044
TI  - Clinical review: Reappraising the concept of immediate defibrillatory attempts
      for out-of-hospital ventricular fibrillation.
AB  - Despite well developed emergency medical services with rapid response advanced
      life support capabilities, survival rates following out-of-hospital ventricular
      fibrillation (VF) have remained bleak in many venues. Generally, these poor
      resuscitation rates are attributed to delays in the performance of basic
      cardiopulmonary resuscitation by bystanders or delays in defibrillation, but
      recent laboratory data suggest that the current standard of immediately providing
      a countershock as the first therapeutic intervention may be detrimental when VF
      is prolonged beyond several minutes. Several studies now suggest that when
      myocardial energy supplies begin to dwindle following more prolonged periods of
      VF, improvements in coronary artery perfusion must first be achieved in order to
      prime the heart for successful return of spontaneous circulation after
      defibrillation. Therefore, before countershocks, certain pharmacologic and/or
      mechanical interventions might take precedence during resuscitative efforts. This
      evolving concept has been substantiated recently by clinical studies, including a
      controlled clinical trial, demonstrating a significant improvement in survival
      when basic cardiopulmonary resuscitation is provided for several minutes before
      the initial countershock. Although this evolving concept differs from current
      standards and may pose a potential problem for automated defibrillator
      initiatives (e.g. public access defibrillation), successful defibrillation and
      return of spontaneous circulation have been rendered more predictable by evolving
      technologies that can score the VF waveform signal and differentiate between
      those who can be shocked immediately and those who should receive other
      interventions first.

PMID- 14975045
TI  - Statistics review 8: Qualitative data - tests of association.
AB  - This review introduces methods for investigating relationships between two
      qualitative (categorical) variables. The chi2 test of association is described,
      together with the modifications needed for small samples. The test for trend, in
      which at least one of the variables is ordinal, is also outlined. Risk
      measurement is discussed. The calculation of confidence intervals for proportions
      and differences between proportions are described. Situations in which samples
      are matched are considered.

PMID- 14975046
TI  - Should central venous catheters be used to drain pleural effusions?

PMID- 14975048
TI  - 8th Annual Toronto Critical Care Medicine Symposium, 30 October-1 November 2003,
      Toronto, Ontario, Canada.

PMID- 14975049
TI  - Remifentanil versus fentanyl for analgesia based sedation to provide patient
      comfort in the intensive care unit: a randomized, double-blind controlled trial
      [ISRCTN43755713].
AB  - INTRODUCTION: This double-blind, randomized, multicentre study was conducted to
      compare the efficacy and safety of remifentanil and fentanyl for intensive care
      unit (ICU) sedation and analgesia. METHODS: Intubated cardiac, general
      postsurgical or medical patients (aged >/= 18 years), who were mechanically
      ventilated for 12-72 hours, received remifentanil (9 microgram/kg per hour; n =
      77) or fentanyl (1.5 microgram/kg per hour; n = 75). Initial opioid titration was
      supplemented with propofol (0.5 mg/kg per hour), if required, to achieve optimal
      sedation (i.e. a Sedation-Agitation Scale score of 4). RESULTS: The mean
      percentages of time in optimal sedation were 88.3% for remifentanil and 89.3% for
      fentanyl (not significant). Patients with a Sedation-Agitation Scale score of 4
      exhibited significantly less between-patient variability in optimal sedation on
      remifentanil (variance ratio of fentanyl to remifentanil 1.84; P = 0.009). Of
      patients who received fentanyl 40% required propofol, as compared with 35% of
      those who received remifentanil (median total doses 683 mg and 378 mg,
      respectively; P = 0.065). Recovery was rapid (median time to extubation: 1.1
      hours for remifentanil and 1.3 hours for fentanyl; not significant). Remifentanil
      patients who experienced pain did so for significantly longer during extubation
      (6.5% of the time versus 1.4%; P = 0.013), postextubation (10.2% versus 3.6%; P =
      0.001) and post-treatment (13.5% versus 5.1%; P = 0.001), but they exhibited
      similar haemodynamic stability with no significant differences in adverse event
      incidence. CONCLUSION: Analgesia based sedation with remifentanil titrated to
      response provided effective sedation and rapid extubation without the need for
      propofol in most patients. Fentanyl was similar, probably because the dosing
      algorithm demanded frequent monitoring and adjustment, thereby preventing over
      sedation. Rapid offset of analgesia with remifentanil resulted in a greater
      incidence of pain, highlighting the need for proactive pain management when
      transitioning to longer acting analgesics, which is difficult within a double
      blind study but would be quite possible under normal circumstances.

PMID- 14975050
TI  - Procalcitonin as a marker of bacterial infection in the emergency department: an
      observational study.
AB  - INTRODUCTION: Procalcitonin (PCT) has been proposed as a marker of infection in
      critically ill patients; its level is related to the severity of infection. We
      evaluated the value of PCT as a marker of bacterial infection for emergency
      department patients. METHODS: This prospective observational study consecutively
      enrolled 120 adult atraumatic patients admitted through the emergency department
      of a 3000-bed tertiary university hospital in May 2001. Fifty-eight patients were
      infected and 49 patients were not infected. The white blood cell counts, the
      serum C-reactive protein (CRP) level (mg/l), and the PCT level (ng/ml) were
      compared between the infected and noninfected groups of patients. RESULTS: A
      white blood cell count >12,000/mm3 or <4000/mm3 was present in 36.2% of the
      infected patients and in 18.4% of the noninfected patients. The best cut-off
      serum levels for PCT and CRP, identified using the Youden's Index, were 0.6 ng/ml
      and 60 mg/l, respectively. Compared with CRP, PCT had a comparable sensitivity
      (69.5% versus 67.2%), a lower specificity (64.6% versus 93.9%), and a lower area
      under the receiver operating characteristic curve (0.689 versus 0.879). PCT
      levels, but not CRP levels, were significantly higher in bacteremic and septic
      shock patients. Multivariate logistic regression identified that a PCT level >/=
      2.6 ng/ml was independently associated with the development of septic shock (odds
      ratio, 38.3; 95% confidence interval, 5.6-263.5; P < 0.001). CONCLUSIONS: PCT is
      not a better marker of bacterial infection than CRP for adult emergency
      department patients, but it is a useful marker of the severity of infection.

PMID- 14975052
TI  - The effects of different weaning modes on the endocrine stress response.
AB  - INTRODUCTION: The aim of the present study was to investigate the effects of the
      stress response on plasma insulin, cortisol, glucose, and urinary vanilmandelic
      acid during weaning and after extubation, using pressure support (PS), continuous
      positive airway pressure (CPAP) and T-piece modes. METHODS: Sixty patients were
      randomly divided into three groups (n = 20). The PS group received FiO2 </= 0.4,
      PS </= 10 cmH2O, and positive end expiratory pressure </= 5 cmH2O for 2 hours.
      The CPAP group was given FiO2 </= 0.4 and CPAP 5 </= cmH2O for 2 hours. The T
      piece group (group T) received 4 l/min oxygen via a T-piece for 2 hours. After 1
      hour and 2 hours in their respective weaning modes, blood and urine samples were
      taken for insulin, cortisol, glucose and vanilmandelic acid measurements. Forty
      eight hours after extubation, blood and urine samples were again taken. RESULTS:
      Plasma insulin was greater in group T than in the PS and CPAP groups (P < 0.01
      and P < 0.01). The plasma cortisol concentration was greater in group T than in
      group PS during weaning (P < 0.05) and after extubation (P < 0.05). Blood glucose
      concentrations were greater in group T than in the other groups (both P < 0.01)
      both during weaning and post extubation. Urine vanilmandelic acid was greater in
      group T than in the other groups during weaning and after extubation (both P <
      0.001). CONCLUSION: Weaning via the T-piece caused a greater stress response than
      the PS and CPAP modes.

PMID- 14975051
TI  - Offset of pharmacodynamic effects and safety of remifentanil in intensive care
      unit patients with various degrees of renal impairment.
AB  - INTRODUCTION: This open label, multicentre study was conducted to assess the
      times to offset of the pharmacodynamic effects and the safety of remifentanil in
      patients with varying degrees of renal impairment requiring intensive care.
      METHODS: A total of 40 patients, who were aged 18 years or older and had
      normal/mildly impaired renal function (estimated creatinine clearance >/= 50
      ml/min; n = 10) or moderate/severe renal impairment (estimated creatinine
      clearance <50 ml/min; n = 30), were entered into the study. Remifentanil was
      infused for up to 72 hours (initial rate 6-9 microgram/kg per hour), with
      propofol administered if required, to achieve a target Sedation-Agitation Scale
      score of 2-4, with no or mild pain. RESULTS: There was no evidence of increased
      offset time with increased duration of exposure to remifentanil in either group.
      The time to offset of the effects of remifentanil (at 8, 24, 48 and 72 hours
      during scheduled down-titrations of the infusion) were more variable and were
      statistically significantly longer in the moderate/severe group than in the
      normal/mild group at 24 hours and 72 hours. These observed differences were not
      clinically significant (the difference in mean offset at 72 hours was only 16.5
      min). Propofol consumption was lower with the remifentanil based technique than
      with hypnotic based sedative techniques. There were no statistically significant
      differences between the renal function groups in the incidence of adverse events,
      and no deaths were attributable to remifentanil use. CONCLUSION: Remifentanil was
      well tolerated, and the offset of pharmacodynamic effects was not prolonged
      either as a result of renal dysfunction or prolonged infusion up to 72 hours.

PMID- 14975053
TI  - Endotoxin neutralization and anti-inflammatory effects of tobramycin and
      ceftazidime in porcine endotoxin shock.
AB  - INTRODUCTION: Antibiotics used for treatment of severe bacterial infections have
      been shown to exert effects on the inflammatory response in addition to their
      antibacterial effects. The aim of the present study was to investigate whether
      the biological effects of endotoxin in a porcine model could be neutralized by
      tobramycin, and whether tobramycin or ceftazidime was able to modulate the
      inflammatory response. METHOD: Thirteen piglets were subjected to endotoxin
      infusion at an initial rate of 4 microgram/kg per hour, which was reduced to 1
      microgram/kg per hour after 30 min. Before endotoxin infusion, the animals
      received saline (n = 4), ceftazidime (n = 5), or tobramycin (n = 4) at clinically
      relevant doses. Physiological parameters were measured and blood samples were
      taken hourly for 6 hours for analysis of tumour necrosis factor-alpha, IL-6 and
      endotoxin concentrations. RESULTS: All of the animals exhibited physiological
      signs of severe sepsis without major differences between the groups. Plasma
      endotoxin concentration was stable after 1 hour. There were no differences in
      endotoxin concentration or initial tumour necrosis factor-alpha and IL-6
      concentrations between the groups. At 6 hours the IL-6 concentration was
      significantly lower in the ceftazidime group than in the saline group (P < 0.05),
      and in both the ceftazidime and the tobramycin groups there were significantly
      greater reductions from peak values (P < 0.05). CONCLUSION: There was no
      neutralization of the biological effects of endotoxin in this porcine model.
      However, our data indicate a possible anti-inflammatory effect exerted by both
      ceftazidime and tobramycin, which manifested as a significantly greater reduction
      in IL-6 in comparison with the untreated group.

PMID- 14975054
TI  - Multiresistant coagulase-negative staphylococci disseminate frequently between
      intubated patients in a multidisciplinary intensive care unit.
AB  - INTRODUCTION: The intensive care unit is burdened with a high frequency of
      nosocomial infections often caused by multiresistant nosocomial pathogens.
      Coagulase-negative staphylococci (CoNS) are reported to be the third causative
      agent of nosocomial infections and the most frequent cause of nosocomial
      bloodstream infections. CoNS are a part of the normal microflora of skin but can
      also colonize the nasal mucosa, the lower airways and invasive devices. The main
      aim of the present study was to investigate colonization and the rate of cross
      transmissions of CoNS between intubated patients in a multidisciplinary intensive
      care unit. MATERIALS AND METHODS: Twenty consecutive patients, ventilated for at
      least 3 days, were included. Samples were collected from the upper and lower
      airways. All samples were cultured quantitatively and CoNS were identified by
      morphology and biochemical tests. A total of 199 CoNS isolates from 17 patients
      were genetically fingerprinted by pulsed-field gel electrophoresis in order to
      identify clones and to monitor dissemination within and between patients.
      RESULTS: An unexpected high number of transmission events were detected. Five
      genotypes were each isolated from two or more patients, and 14/20 patients were
      involved in at least one and up to eight probable transmission events.
      CONCLUSIONS: A frequent transmission of CoNS was found between patients in the
      intensive care unit. Although transmission of bacteria does not necessarily lead
      to infection, it is nevertheless an indication that infection control measures
      can be improved.

PMID- 14975055
TI  - Application of the Italian version of the Intensive Care Unit Memory tool in the
      clinical setting.
AB  - INTRODUCTION: The aims of the present study were to assess patients' memories of
      their stay in the intensive care unit (ICU) over time, using the Italian version
      of the ICU Memory (ICUM) tool, and to examine the relationship between memory and
      duration of ICU stay and infection. PATIENTS AND METHOD: Adult patients
      consecutively admitted to a four-bed ICU of a university hospital, whose stay in
      the ICU was at least 3 days, were prospectively studied. The ICUM tool was
      administered twice: face to face 1 week after ICU discharge to 93 patients
      (successfully in 87); and by phone after 3 months to 67 patients. Stability of
      memories over time was analyzed using Kappa statistics. RESULTS: Delusional
      memories appeared to be the most persistent recollections over time (minimum
      kappa value = 0.68), followed by feelings (kappa value > 0.7 in three out of six
      memories) and factual memories (kappa value > 0.7 in three out of 11 memories).
      The patients without a clear memory of their stay in the ICU reported a greater
      number of delusional memories than did those with a clear memory. Of patients
      without infection 35% had one or two delusional memories, and 60% of patients
      with infection had one to four delusional memories (P = 0.029). CONCLUSION: The
      ICUM tool is of value in a setting and language different from those in which it
      was created and used. Delusional memories are the most stable recollections, and
      are frequently associated both with lack of clear memory of ICU experience and
      with presence of infection during ICU stay.

PMID- 14975056
TI  - Case report: fatal poisoning with Colchicum autumnale.
AB  - INTRODUCTION: Colchicum autumnale, commonly known as the autumn crocus, contains
      alkaloid colchicine with antimitotic properties. CASE REPORT: A 76-year-old man
      with a history of alcoholic liver disease and renal insufficiency, who mistakenly
      ingested Colchicum autumnale instead of wild garlic (Aliium ursinum), presented
      with nausea, vomiting and diarrhea 12 hours after ingestion. On admission the
      patient had laboratory signs of dehydration. On the second day the patient became
      somnolent and developed respiratory insufficiency. The echocardiogram showed
      heart dilatation with diffuse hypokinesia with positive troponin I. The
      respiratory insufficiency was further deteriorated by pneumonia, confirmed by
      chest X-ray and later on by autopsy. Laboratory tests also revealed
      rhabdomyolysis, coagulopathy and deterioration of renal function and hepatic
      function. The toxicological analysis disclosed colchicine in the patient's urine
      (6 microgram/l) and serum (9 microgram/l) on the second day. Therapy was
      supportive with hydration, vasopressors, mechanical ventilation and antibiotics.
      On the third day the patient died due to asystolic cardiac arrest. DISCUSSION AND
      CONCLUSION: Colchicine poisoning should be considered in patients with
      gastroenterocolitis after a meal of wild plants. Management includes only
      intensive support therapy. A more severe clinical presentation should be expected
      in patients with pre-existing liver and renal diseases. The main reasons for
      death are cardiovascular collapse, respiratory failure and leukopenia with
      infection.

PMID- 14975057
TI  - A new instrument to describe indicators of well-being in old-old patients with
      severe dementia--the Vienna List.
AB  - BACKGROUND: In patients with very severe dementia self-rating of quality of life
      usually is not possible and appropriate instruments for proxy-ratings are not
      available. The aim of this project is to develop an instrument of clinical proxy
      ratings for this population. METHODS: Using electronic instruments, physicians
      and nurses recorded patient behaviour and changes of behaviour over a period of
      one year. Based on these data a list of 65 items was generated and subsequently
      allocated to 14 categories. This list was tested in 217 patients (61-105 yrs)
      with dementia diagnosed according to ICD-10 by both physicians and nurses. The
      severity of dementia was assessed by means of the Global Deterioration Scale
      (GDS) and the Brief Cognitive Rating Scale (BCRS). The Spitzer-Index (proxy
      rating) was used as a global quality of life measure. Activity of daily living
      was rated using the Barthel Index. RESULTS: A factor analysis of the original 65
      items revealed 5 factors (communication, negative affect, bodily contact,
      aggression, and mobility). By stepwise removing items we obtained satisfactory
      internal consistencies of the factors both for nurses' and physicians' ratings.
      The factors were generally unrelated. The validity of the instrument was proven
      by correlations of the factors communication and mobility with the Brief
      Cognitive Rating Scale (BCRS) and the Barthel-Index. CONCLUSION: The results
      demonstrate the reliability and validity of the Vienna List as a proxy rating
      measurement of quality of life in patients with severe dementia. The psychometric
      properties of the scale have to be proved in further studies.

PMID- 14975058
TI  - Overview: Report of a Scientific Working Group on Serious Adverse Events
      following Mectizan(R) treatment of onchocerciasis in Loa loa endemic areas.

PMID- 14975059
TI  - Report of a Scientific Working Group on Serious Adverse Events following
      Mectizan(R) treatment of onchocerciasis in Loa loa endemic areas.
AB  - The occurrence of Serious Adverse Experiences (SAEs) following Mectizan(R)
      treatment of onchocerciasis in Loa loa endemic areas has been increasingly
      reported over the past decade. These SAEs include a severely disabling, and
      potentially fatal, encephalopathy, which appears to correlate with a high load of
      L. loa microfilariae (> 30,000 mf/ml).Previous consultations organized by the
      Mectizan(R) Donation Program (MDP) in 1995 and 1999 have developed useful "case"
      definitions of encephalopathic SAEs following Mectizan(R) treatment and have
      summarized available evidence on its pathogenesis and optimal clinical
      management. At both meetings, the need for better understanding of the
      pathogenesis of the encephalopathy was emphasized, including the need for
      biological and autopsy specimens from the affected cases.Following a
      recommendation at the Joint Action Forum of the African Programme for
      Onchocerciasis Control in December 2001, the MDP, on behalf of the Mectizan(R)
      Expert Committee, organized a Scientific Working Group on L. loa associated SAEs
      following Mectizan(R) treatment in May 2002. The present report includes the
      background, new evidence, conclusions and recommendations from that Scientific
      Working Group. The following points represent a summary of the present status:1.
      Although there are more and better quality clinical and epidemiological data on
      L. loa, the pathogenesis of the Mectizan(R)-related L. loa encephalopathy remains
      obscure.2. Very limited progress has been made in research on the pathogenesis of
      encephalopathy, because of the lack of specimens from cases, and the lack of
      animal models.3. There has been no particular breakthrough in terms of the
      medical management of patients with L. loa encephalopathy; however, a favorable
      outcome usually results from prompt general nursing and nutritional care which
      remain the major interventions.The main recommendations for future actions are as
      follows:1. Validate and update the mapping of L. loa with a combination of remote
      sensing and RAPLOA techniques.2. Conduct an expert analysis of the apparent
      clustering of encephalopathic SAEs reported so far.3. Investigate a possible "pre
      treatment" scheme with high-dose albendazole in L. loa endemic communities at
      high risk of encephalopathic SAEs if treated with Mectizan(R); this study will be
      conducted in collaboration with WHO/TDR.4. Establish a post of Loiasis Technical
      Advisor for research and operational support in Cameroon, to conduct population
      surveys and to facilitate better data collection from SAE cases, including
      postmortem studies as appropriate.5. Investigate the possibility of developing an
      animal model of L. loa encephalopathy; this activity would be linked to the above
      mentioned research agenda in Cameroon.6. Investigate the best care model for
      encephalopathic SAEs, including identification of early warning signs and
      therapeutic interventions.7. Develop further models for health education messages
      needed for community compliance with Mectizan(R) treatment, and family support
      for SAE cases.8. Conduct research studies on the safety of combination therapy of
      Mectizan(R) and albendazole in areas co-endemic for L. loa and lymphatic
      filariasis (LF) with coordination from the relevant technical bodies that oversee
      these issues.The above recommendations will be implemented through a continuing
      collaboration between the interested parties represented at the Scientific
      Working Group, involved in onchocerciasis control and/or the Global Programme to
      Eliminate Lymphatic Filariasis.

PMID- 14975060
TI  - Serious adverse events following treatment with ivermectin for onchocerciasis
      control: a review of reported cases.
AB  - This paper presents a summary of reported cases of Serious Adverse Events (SAEs)
      following treatment with Mectizan(R) (ivermectin, Merck, Sharpe & Dohme) in
      onchocerciasis mass treatment programs from January 1, 1989 to December 31, 2001
      through a passive surveillance system. A total of 207 SAE cases were reported out
      of approximately 165 million reported treatments delivered during the period
      under review, giving rise to a cumulative incidence of 1 reported SAE per 800,000
      reported treatments. The mean age was 40 years and 70% of the cases were males.
      The mean time between ivermectin intake and onset of illness was 1 day. For 57%
      of the cases (n = 118), that was their first exposure to ivermectin. The majority
      of cases were reported from Cameroon (n = 176; 85%) with peaks in the incidence
      of SAE reporting in 1989-1991 and 1994-1995 when the program expanded to
      ivermectin-naive populations. Fifty-five percent of the cases from Cameroon (i.e.
      97 out of 176 cases) were encephalopathic and were reported from the central
      southern region of the country; two-thirds of these cases were 'probable' or
      'possible' cases of Loa loa encephalopathy temporally related to ivermectin
      treatment. Reporting bias may explain some but not all of the differences in SAE
      reporting between the 34 onchocerciasis-endemic countries that have, or have had,
      mass treatment programs. Further research is needed to understand the apparent
      clustering of encephalopathy cases in central-southern Cameroon since L. loa
      infection alone probably does not explain the increased incidence of this type of
      SAE from this region.

PMID- 14975061
TI  - Clinical picture, epidemiology and outcome of Loa-associated serious adverse
      events related to mass ivermectin treatment of onchocerciasis in Cameroon.
AB  - In August 2002, 65 cases of Loa-associated neurological Serious Adverse Events
      were reported after ivermectin treatment. The first signs, occurring within the
      12-24 hours following treatment, included fatigue, generalized arthralgia, and
      sometimes agitation, mutism, and incontinence. Disorders of consciousness,
      including coma, generally appeared between 24 and 72 hours, and showed a rapid
      variation with time. The most frequent objective neurological signs were
      extrapyramidal. The patients presented with haemorrhages of the conjunctiva and
      of the retina. Biological examinations showed a massive Loa microfilaruria, the
      passage of Loa microfilariae into the cerebrospinal fluid, haematuria, and an
      increase in the C-reactive protein, all of which have been correlated with the
      high intensity of the initial Loa microfilaraemia. Eosinophil counts decreased
      dramatically within the first 24 hours, and then rose again rapidly.
      Electroencephalograms suggested the existence of a diffuse pathological process
      within the first weeks; the abnormalities disappearing after 3-6 months. Death
      may occur when patients are not properly managed, i.e. in the absence of good
      nursing. However, some patients who recovered showed sequelae such as aphasia,
      episodic amnesia, or extrapyramidal signs. The main risk factor for these
      encephalopathies is the intensity of the initial Loa microfilaraemia. The
      disorders of consciousness may occur when there are >50,000 Loa microfilariae per
      ml. The possible roles of co-factors, such as Loa strains, genetic predisposition
      of individuals, co-infestations with other parasites, or alcohol consumption,
      seem to be minor but they should be considered. The mechanisms of the post
      ivermectin Loa-related encephalopathies should be investigated to improve the
      management of patients developing the condition.

PMID- 14975062
TI  - Possible pathogenic pathways in the adverse clinical events seen following
      ivermectin administration to onchocerciasis patients.
AB  - BACKGROUND: Reactions are commonly associated with the chemotherapy of
      onchocerciasis. However unmanageable reactions are uncommon when ivermectin
      (Mectizan(R)) is used for the treatment of this infection, and this drug has
      proved to be a great improvement over previously used agents. Serious adverse
      events (SAE) nevertheless have occurred, and there is considerable concern about
      the negative effect such events may have on mass drug administration
      programs.This paper reviews the basic pathogenic mechanisms that can be involved
      in the destruction of microfilaria by chemotherapeutic agents. A central
      challenge to filarial chemotherapy is the need to remove parasites from
      biologically sensitive tissues, a more difficult medical challenge than
      eliminating nematodes from the gastrointestinal tract.Explanations for the
      etiology of the serious adverse reactions occurring with ivermectin treatment in
      specific geographic areas where there is coincident heavy Loa loa infections are
      hampered by a lack of specific pathological case material. Ways to investigate
      these possibilities are reviewed. Possible pathogenic mechanisms include embolic
      vascular pathology accompanied by local inflammation, blood brain barrier mdr1
      abnormalities, and genetic predisposition to excessive inflammatory responses.
      CONCLUSION: It is important to keep ivermectin, and all its associated adverse
      clinical events, in perspective with the many other chemotherapeutic agents in
      general use - many of which produce serious adverse events even more frequently
      than does ivermectin. Currently available evidence indicates that the
      pathogenesis of the Loa-associated adverse reactions are probably related to
      inflammatory responses to microfilariae in specific tissues. However, the
      possibility of genetic predispositions to pathology should also be considered.

PMID- 14975063
TI  - Clinical picture and outcome of Serious Adverse Events in the treatment of
      Onchocerciasis.
AB  - Ivermectin (Mectizan(R)) is the only drug currently recommended for the treatment
      and control of onchocerciasis. Serious adverse events rarely occur during
      treatment, except in subjects heavily infected with Loa Loa. This review of drug
      related serious adverse events in the treatment of onchocerciasis therefore
      revisited the pre-Mectizan(R) reference drugs, DEC and suramin, and other
      candidate drugs studied extensively for the treatment of human onchocerciasis.
      The benzimidazole carbamate derivatives and the antibiotic doxycycline were
      excluded, since no serious adverse events have been reported regarding their use.
      Using recommended definitions, serious adverse events reported or observed after
      the use of each drug were summarised, the level of attribution determined, and
      the results tabulated. Prominence was given to treatment-related deaths. The
      clinical picture of severe symptomatic postural hypotension is described and used
      to illustrate the difference between the severity and the seriousness of an
      adverse event. The epidemiology, management and outcome of serious adverse events
      are presented. The role of future research is discussed.

PMID- 14975064
TI  - Loa loa encephalopathy temporally related to ivermectin administration reported
      from onchocerciasis mass treatment programs from 1989 to 2001: implications for
      the future.
AB  - Of the 207 Serious Adverse Events (SAEs) following treatment with Mectizan(R)
      (ivermectin, Merck, Sharpe & Dohme) that were reported from 1989 to 2001 through
      the passive SAE surveillance system required of all onchocerciasis mass treatment
      programs, 65 were cases of 'Probable' or 'Possible' Loa loa Encephalopathy
      temporally Related to treatment with Mectizan(R) (PLERM).A retrospective analysis
      of these 65 PLERM cases revealed that 97% were from southern Cameroon, 85% were
      male and 93% were being treated with ivermectin for the first time. The mean time
      to onset of symptoms was 1.7 days (95% CI: 1.3, 2.2) but the mean time to
      receiving medical attention after the onset of symptoms was 2.0 days (95% CI:
      1.5, 2.6). Hospitalization was reported in 53 cases with a mean duration of 27.5
      days (95% CI: 13.3, 41.6, n = 35). Clinical outcome was reported in 34 cases:
      64.7% recovered fully, 11.8% had partial neurologic deficit and 23.5% died. For
      the 32 cases where quantitative L. loa data were reported, the arithmetic means
      with 95% confidence intervals were for 1) peripheral blood: pre-treatment -
      164,250 mf/ml (79,537, 248,963; n = 4); post-treatment within 1 month - 3926
      mf/ml (2,128, 5,725; n = 21) and within 5 to 6 months - 7800 mf/ml (3417, 12,183;
      n = 7); and for 2) cerebrospinal fluid: 32 mf/ml (7, 37; n = 10) within 1 month
      post-treatment.Pending further research on practical methods to exclude
      individuals with high intensity L. loa infection from onchocerciasis mass
      treatment programs, more emphasis should be placed on surveillance and monitoring
      to ensure early recognition, referral and management of SAEs, during the first 2
      years when majority of the population is presumably naive to ivermectin.

PMID- 14975065
TI  - Ivermectin: does P-glycoprotein play a role in neurotoxicity?
AB  - The macrocyclic lactone ivermectin (Mectizan(R)) is widely used for the control
      of human filarial infections, particularly as a donated product for
      onchocerciasis and lymphatic filariasis. In the case of control of lymphatic
      filariasis in Africa, it is used in combination with donated albendazole. In
      areas co-endemic for Onchocerciasis and Loa loa, serious adverse reactions have
      been observed in patients with apparently high microfilaria counts of Loa loa.
      Recent findings suggest that the severe central nervous system side effects seen
      in various vertebrates following ivermectin treatment may be due to an absence
      of, or functional deficiency in P-glycoprotein. P-glycoprotein is expressed in
      the apical membrane of brain capillary epithelial cells and is responsible for
      limiting the brain penetration of a range of compounds. Toxicity of ivermectin in
      some collie dogs may be explained by a 4-bp deletion mutation of the mdr1 gene
      resulting in a frame shift, generating stop codons that prematurely terminate
      synthesis of P-glycoprotein. Additionally, sub-populations of CF-1 identified as
      expressing reduced levels of P-glycoprotein exhibit increased toxicity to
      substrates of this transporter. Furthermore, while the traditional view of drug
      drug interactions is alteration in drug clearance mediated through a change in
      hepatic drug metabolism, some of these changes may arise through competition for
      binding sites on P-glycoprotein in the blood-brain barrier, resulting in reduced
      extracellular efflux and enhanced CNS toxicity. In conclusion, P-glycoprotein is
      an integral component of the human blood brain barrier and plays a central role
      in limiting drug uptake into the brain. Altered expression or function of p
      glycoprotein could conceivably allow elevation of brain concentrations of
      ivermectin and produce severe neurotoxicity. This might arise through a genetic
      polymorphism in p-glycoprotein or co-administration of ivermectin with a drug or
      foodstuff that might inhibit this efflux transporter.

PMID- 14975066
TI  - A Framework for Decision-Making for Mass Distribution of Mectizan(R) in Areas
      Endemic for Loa loa.
AB  - BACKGROUND: The occurrence of Loa loa encephalopathy following mass treatment of
      onchocerciasis with Mectizan(R) has adversely affected onchocerciasis control
      efforts in central Africa. Persons with very high densities of L. loa
      microfilaremia are at increased risk of encephalopathy, but little is known about
      the geographic distribution of these persons within central Africa. RAPLOA, a new
      technique that correlates the proportion of community members reporting a history
      of eyeworm with the prevalence of high-intensity L. loa microfilaremia in that
      community, may be useful for rapid assessment of areas at potential risk of
      treatment-related L. loa encephalopathy. Validation of RAPLOA is ongoing. The
      operational and risk-reduction advantages of RAPLOA over the current technique of
      village-by-village rapid epidemiologic assessment for onchocerciasis (REA) are
      unknown. METHODS: We developed a decision model to compare four strategies for
      minimizing sequelae of L. loa encephalopathy following mass treatment with
      Mectizan(R) in areas co-endemic for onchocerciasis and loiasis: REA; RAPLOA with
      threshold eyeworm prevalences of 40% and 20% (RAPLOA-40 and RAPLOA-20,
      respectively); and combined REA/RAPLOA-40. RESULTS: In the model, all four
      strategies significantly reduced risk of death and neurologic complications from
      L. loa encephalopathy, but RAPLOA-20 and REA resulted in half as many such cases
      as did RAPLOA-40 or combined REA/RAPLOA-40. CONCLUSION: RAPLOA is likely to be
      useful programmatically in reducing risk of L. loa encephalopathy following mass
      treatment with Mectizan(R). It also may be cost-saving. Before full-scale
      implementation, additional data are needed on geographic clustering of high
      density L. loa microfilaremia and on RAPLOA's reliability and cost.

PMID- 14975067
TI  - Programmatic and Communication Issues in Relation to Serious Adverse Events
      Following Ivermectin Treatment in areas Co-endemic for Onchocerciasis and
      Loiasis.
AB  - In areas co-endemic for loiasis and onchocerciasis, the classic Community
      Directed Treatment using ivermectin (Mectizan(R)) must be adapted as additional
      program activities, better communication and tighter control of ivermectin stocks
      are required to minimize risk and manage serious adverse events following
      ivermectin treatment in patients co-infected with Loa loa. The importance of
      these serious adverse events on community participation in onchocerciasis control
      efforts has not been adequately studied. Program implementers do not as of yet
      fully understand the psychological impact of serious adverse events on
      communities and therefore have not designed communication strategies that
      adequately address the real concerns of community members. It is clear, however,
      that along with an effective case detection and management strategy, a reinforced
      communication strategy will be required to motivate at least 65% of the total
      population in onchocerciasis and loiasis co-endemic areas to participate in the
      treatment program and to take ivermectin over an extended period. This strategy
      must be based on research undertaken at the community level in order to address
      the concerns, fears and issues associated with adverse events due to ivermectin -
      to ensure that communities believe that the benefits of taking ivermectin
      outweigh the risks. In addition to an overall increase in the time required to
      sustain onchocerciasis control programs in co-endemic areas, each aspect of the
      reinforced program and communication strategy - rapid epidemiological
      assessments, materials development, training, advocacy, community sensitization
      and mobilization, case management and counselling, supervision, monitoring and
      evaluation will require additional resources and support from all stakeholders
      concerned.

PMID- 14975069
TI  - Proceedings of the Genetic Analysis Workshop 13: analysis of longitudinal family
      data for complex diseases and related risk factors. November 11-14, 2002. New
      Orleans, Louisiana, USA.

PMID- 14975068
TI  - Off-label indications for atypical antipsychotics: A systematic review.
AB  - INTRODUCTION: With the introduction of newer atypical antipsychotic agents, a
      question emerged, concerning their use as complementary pharmacotherapy or even
      as monotherapy in mental disorders other than psychosis. MATERIAL AND METHOD:
      MEDLINE was searched with the combination of each one of the key words:
      risperidone, olanzapine and quetiapine with key words that refered to every DSM
      IV diagnosis other than schizophrenia and other psychotic disorders, bipolar
      disorder and dementia and memory disorders. All papers were scored on the basis
      of the JADAD index. RESULTS: The search returned 483 papers. The selection
      process restricted the sample to 59 papers concerning Risperidone, 37 concerning
      Olanzapine and 4 concerning Quetiapine (100 in total). Ten papers (7 concerning
      Risperidone and 3 concerning Olanzapine) had JADAD index above 2. Data suggest
      that further research would be of value concerning the use of risperidone in the
      treatment of refractory OCD, Pervasive Developmental disorder, stuttering and
      Tourette's syndrome, and the use of olanzapine for the treatment of refractory
      depression and borderline personality disorder. DISCUSSION: Data on the off-label
      usefulness of newer atypical antipsychotics are limited, but positive cues
      suggest that further research may provide with sufficient hard data to warrant
      the use of these agents in a broad spectrum of psychiatric disorders, either as
      monotherapy, or as an augmentation strategy.

PMID- 14975070
TI  - Description of the Framingham Heart Study data for Genetic Analysis Workshop 13.

PMID- 14975071
TI  - Genetic Analysis Workshop 13: simulated longitudinal data on families for a
      system of oligogenic traits.
AB  - The Genetic Analysis Workshop 13 simulated data aimed to mimic the major features
      of the real Framingham Heart Study data that formed Problem 1, but under a known
      inheritance model and with 100 replicates, so as to allow evaluation of the
      statistical properties of various methods. The pedigrees used were the 330 real
      pedigree structures (comprising 4692 individuals) with some minor changes to
      protect confidentiality. Fifty trait genes and 399 microsatellite markers were
      simulated by gene dropping on 22 autosomal chromosomes. Assuming random
      ascertainment of families, a system of eight longitudinal quantitative traits
      (designed to be similar to those in the real data) was generated with a wide
      range of heritabilities, including some pleiotropic and interactive effects.
      Genes could affect either the baseline level or the rate of change of the
      phenotype. Hypertension diagnosis and treatment were simulated with treatment
      availability, compliance, and efficacy depending on calendar year. Nongenetic
      traits of smoking and alcohol were generated as covariates for other traits.
      Death was simulated as a hazard rate depending upon age, sex, smoking,
      cholesterol, and systolic blood pressure. After the complete data were simulated,
      missing data indicators were generated based on logistic models fitted to the
      real data, involving the subject's history of previous missing values, together
      with that of their spouses, parents, siblings, and offspring, as well as marital
      status, only-child indicators, current value at certain simulated traits, and the
      data collection pattern on the cohort into which each subject was ascertained.

PMID- 14975072
TI  - Variance components linkage analysis for adjusted systolic blood pressure in the
      Framingham Heart Study.
AB  - We performed variance components linkage analysis in nuclear families from the
      Framingham Heart Study on nine phenotypes derived from systolic blood pressure
      (SBP). The phenotypes were the maximum and mean SBP, and SBP at age 40, each
      analyzed either uncorrected, or corrected using two subsets of
      epidemiological/clinical factors. Evidence for linkage to chromosome 8p was
      detected with all phenotypes except the uncorrected maximum SBP, suggesting this
      region harbors a gene contributing to variation in SBP.

PMID- 14975073
TI  - Use of a random coefficient regression (RCR) model to estimate growth parameters.
AB  - We used a random coefficient regression (RCR) model to estimate growth parameters
      for the time series of observed serum glucose levels in the Replicate 1 of the
      Genetic Analysis Workshop 13 simulated data. For comparison, a two time-point
      interval was also selected and the slope between these two observations was
      calculated. This process yielded four phenotypes: the RCR growth phenotype, a two
      time-point slope phenotype, and Time 1 and Time 2 serum glucose level phenotypes.
      These four phenotypes were used for linkage analyses on simulated chromosomes 5,
      7, 9, and 21, those chromosomes that contained loci affecting the growth course
      for serum glucose levels. The linkage analysis of the RCR-derived phenotype
      showed overwhelming evidence for linkage at one locus (LOD 65.78 on chromosome
      5), while showing elevated but nonsignificant LOD scores for two other loci (LOD
      1.25 on chromosome 7, LOD 1.10 on chromosome 9), and no evidence of linkage for
      the final locus. The two time-point slope phenotype showed evidence for linkage
      at one locus (LOD 4.16 on chromosome 5) but no evidence for linkage at any of the
      other loci. A parallel cross-sectional approach, using as input phenotypes the
      endpoints of the two-point slope phenotype, gave strong linkage results for the
      major locus on chromosome 5 (maximal LOD scores of 17.90 and 27.24 for Time 1 and
      Time 2, respectively) while showing elevated but nonsignificant linkage results
      on chromosome 7 (maximal LOD scores of 1.71 and 1.48) and no evidence for linkage
      at the two remaining loci. The RCR growth parameter showed more power to detect
      linkage to the major locus than either the cross-sectional or two-point slope
      approach, but the cross-sectional approach gave a higher maximal LOD score for
      one of the minor loci.

PMID- 14975074
TI  - Linkage analysis of a derived glucose phenotype in the Genetic Analysis Workshop
      13 simulated data using a variety of Haseman-Elston based regression methods.
AB  - A variety of Haseman-Elston type regression procedures were used to perform a
      genome scan across five chromosomes, using replicates 1-5 of the Genetic Analysis
      Workshop 13 simulated data. The traits of interest were variables corresponding
      to 'baseline' and 'slope' effects derived from the fasting glucose phenotypes.
      Performance in terms of detecting the locations of known trait loci was poor for
      all methods, even when all five replicates were combined to produce a large data
      set (9230 sib pairs). All methods performed well, however, when applied to new
      simulated data in which the true genetic effects were allowed to explain a
      greater proportion of the overall variance.

PMID- 14975075
TI  - Quantitative trait linkage analysis of longitudinal change in body weight.
AB  - One of the great strengths of the Framingham Heart Study data, provided for the
      Genetic Analysis Workshop 13, is the long-term survey of phenotypic data. We used
      this unique data to create new phenotypes representing the pattern of
      longitudinal change of the provided phenotypes, especially systolic blood
      pressure and body weight. We performed a linear regression of body weight and
      systolic blood pressure on age and took the slopes as new phenotypes for
      quantitative trait linkage analysis using the SOLAR package. There was no
      evidence for heritability of systolic blood pressure change. Heritability was
      estimated as 0.15 for adult life "body weight change", measured as the regression
      slope, and "body weight gain" (including only individuals with a positive
      regression slope), and as 0.22 for body weight "change up to 50" (regression
      slope of weight on age up to an age of 50). With multipoint analysis, two regions
      on the long arm of chromosome 8 showed the highest LOD scores of 1.6 at 152 cM
      for "body weight change" and of >1.9 around location 102 cM for "body weight
      gain" and "change up to 50". The latter two LOD scores almost reach the threshold
      for suggestive linkage. We conclude that the chromosome 8 region may harbor a
      gene acting on long-term body weight regulation, thereby contributing to the
      development of the metabolic syndrome.

PMID- 14975076
TI  - An autosome-wide search using longitudinal data for loci linked to type 2
      diabetes progression.
AB  - A genome-wide screen was conducted for type 2 diabetes progression genes using
      measures of elevated fasting glucose levels as quantitative traits from the
      offspring enrolled in the Framingham Heart Study. We analyzed young (20-34 years)
      and old (>or= 35 years) subjects separately, using single-point and multipoint
      sibpair analysis, because of the possible differential impact of progression on
      the groups of interest. We observed significant linkage with change in fasting
      glucose levels on 1q25-32 (p = 5.21 x 10(-8)), 3p26.3-21.31 (p = 1 x 10(-11)),
      8q23.1-24.13 (p = 2.94 x 10(-6)), 9p24.1-21.3 (p = 7 x 10(-7)), and 18p11.31
      q22.1 (p < 10(-11)). The evidence for linkage on chromosomes 8 and 18 was
      consistent for the subset of study participants aged 43 through 55 years.

PMID- 14975077
TI  - Detecting susceptibility genes in case-control studies using set association.
AB  - Complex diseases are generally caused by intricate interactions of multiple genes
      and environmental factors. Most available linkage and association methods are
      developed to identify individual susceptibility genes assuming a simple disease
      model blind to any possible gene - gene and gene - environmental interactions. We
      used a set association method that uses single-nucleotide polymorphism markers to
      locate genetic variation responsible for complex diseases in which multiple genes
      are involved. Here we extended the set association method from bi-allelic to
      multiallelic markers. In addition, we studied the type I error rates and power
      for both approaches using simulations based on the coalescent process. Both bi
      allelic set association (BSA) and multiallelic set association (MSA) tests have
      the correct type I error rates. In addition, BSA and MSA can have more power than
      individual marker analysis when multiple genes are involved in a complex disease.
      We applied the MSA approach to the simulated data sets from Genetic Analysis
      Workshop 13. High cholesterol level was used as the definitive phenotype for a
      disease. MSA failed to detect markers with significant linkage disequilibrium
      with genes responsible for cholesterol level. This is due to the wide spacing
      between the markers and the lack of association between the marker loci and the
      simulated phenotype.

PMID- 14975078
TI  - Using simultaneous equation modeling for defining complex phenotypes.
AB  - BACKGROUND: Interactions between multiple biological phenotypes are difficult to
      model. Simultaneous equation modelling (SEM), as used in econometric modelling,
      may prove an effective tool for this problem. Generalized linear models were used
      to derive the structural equations defining the interactions between cholesterol,
      glucose, triglycerides and high-density lipoprotein cholesterol (HDL-C). These
      structural equations were then applied, using SEM, to Cohort 2 data (replicates 1
      100) to estimate the phenotypic structure underlying the simulation. The goal was
      to determine if this empiric method of deriving structural equations for use in
      SEM was able to recover the simulation model better than generalized linear
      models. RESULTS: First, the underlying structural equations were estimated using
      generalized linear model techniques, which found strong a relationship between
      glucose, triglycerides and HDL-C. Using these structural equations, I used SEM to
      evaluate these relationships jointly. I found that a combination of the empiric
      structural equations and the SEM method was better at recovering the underlying
      simulated relationship between biologic measures than generalized linear
      modelling. CONCLUSION: The empiric SEM procedure presented here estimated
      different relationships between dependent variables than generalized linear
      modelling. The SEM procedure using empirically developed structural equations was
      able to recover the underlying simulation relationship partially and thus holds
      promise as a technique for complex phenotype analysis. Robust methods for
      determining the structural equations must be developed for application of SEM to
      population data.

PMID- 14975079
TI  - Are there mappable genes for family resemblance for the magnitude of intra
      individual variation in systolic blood pressure?
AB  - BACKGROUND: The genetic regulation of variation in intra-individual fluctuations
      in systolic blood pressure over time is poorly understood. Analysis of the
      magnitude of the average fluctuation of a person's systolic blood pressure around
      his or her age-adjusted trend line, however, shows moderate, albeit significant,
      family resemblance in Cohort 1 of the Framingham Heart Study. To determine
      whether genomic regions affecting this phenotype could be identified, we pursued
      a "model-free" multipoint quantitative linkage analysis. RESULTS: Two different
      linkage methods revealed multiple nominally significant signals, two to four of
      which are "replicated" in Cohort 2. When both cohorts are assembled into extended
      pedigrees, three linkage signals remain nominally significant by one or both
      methods. CONCLUSION: Any or all of the genomic regions in the vicinity of
      D5S1456, D11S2359, and D20S470 may contain elements that regulate systolic blood
      pressure homeostasis.

PMID- 14975080
TI  - Genome-wide linkage analysis of longitudinal phenotypes using sigma2A random
      effects (SSARs) fitted by Gibbs sampling.
AB  - The study of change in intermediate phenotypes over time is important in
      genetics. In this paper we explore a new approach to phenotype definition in the
      genetic analysis of longitudinal phenotypes. We utilized data from the
      longitudinal Framingham Heart Study Family Cohort to investigate the familial
      aggregation and evidence for linkage to change in systolic blood pressure (SBP)
      over time. We used Gibbs sampling to derive sigma-squared-A-random-effects
      (SSARs) for the longitudinal phenotype, and then used these as a new phenotype in
      subsequent genome-wide linkage analyses. Additive genetic effects (sigma2A.time)
      were estimated to account for approximately 9.2% of the variance in the rate of
      change of SBP with age, while additive genetic effects (sigma2A) were estimated
      to account for approximately 43.9% of the variance in SBP at the mean age. The
      linkage results suggested that one or more major loci regulating change in SBP
      over time may localize to chromosomes 2, 3, 4, 6, 10, 11, 17, and 19. The results
      also suggested that one or more major loci regulating level of SBP may localize
      to chromosomes 3, 8, and 14. Our results support a genetic component to both SBP
      and change in SBP with age, and are consistent with a complex, multifactorial
      susceptibility to the development of hypertension. The use of SSARs derived from
      quantitative traits as input to a conventional linkage analysis appears to be
      valuable in the linkage analysis of genetically complex traits. We have now
      demonstrated in this paper the use of SSARs in the context of longitudinal family
      data.

PMID- 14975081
TI  - Genome-wide linkage analysis of systolic blood pressure: a comparison of two
      approaches to phenotype definition.
AB  - Problem 1 of the Genetic Analysis Workshop 13(GAW13) contains longitudinal data
      of cardiovascular measurements from 330 pedigrees. The longitudinal data
      complicates the phenotype definition because multiple measurements are taken on
      each individual. To address this complication, we propose an approach that uses
      generalized estimating equations to obtain residuals for each time point for each
      person. The mean residual is then taken as the new phenotype with which to use in
      a variance components linkage analysis. We compare our phenotype definition
      approach to an approach that first reduces the multiple measurements to a single
      measurement and then models these summary statistics as regression terms in a
      variance components analysis. For each approach, multipoint linkage analysis was
      performed using the residuals and the SOLAR computer program. Our results show
      little difference between the methods based on the LOD scores.

PMID- 14975082
TI  - The genetics of cross-sectional and longitudinal body mass index.
AB  - There has been a lack of consistency in detecting chromosomal loci that are
      linked to obesity-related traits. This may be due, in part, to the phenotype
      definition. Many studies use a one-time, single measurement as a phenotype while
      one's weight often fluctuates considerably throughout adulthood. Longitudinal
      data from the Framingham Heart Study were used to derive alternative phenotypes
      that may lead to more consistent findings. Body mass index (BMI), a measurement
      for obesity, is known to increase with age and then plateau or decline slightly;
      the decline phase may represent a threshold or survivor effect. We propose to use
      the weight gain phase of BMI to derive phenotypes useful for linkage analysis of
      obesity. Two phenotypes considered in the present study are the average of and
      the slope of the BMI measurements in the gain phase (gain mean and gain slope).
      For comparison, we also considered the average of all BMI measurements available
      (overall mean). Linkage analysis using the gain mean phenotype exhibited two
      markers with LOD scores greater than 3, with the largest score of 3.52 on
      chromosome 4 at ATA2A03. In contrast, no LOD scores greater than 3 were observed
      when overall mean was used. The gain slope produced weak evidence for linkage on
      chromosome 4 with a multipoint LOD score of 1.77 at GATA8A05. Our analysis shows
      how omitting the decline phase of BMI in the definition of obesity phenotypes can
      result in evidence for linkage which might have been otherwise overlooked.

PMID- 14975083
TI  - Empirically derived phenotypic subgroups - qualitative and quantitative trait
      analyses.
AB  - BACKGROUND: The Framingham Heart Study has contributed a great deal to advances
      in medicine. Most of the phenotypes investigated have been univariate traits
      (quantitative or qualitative). The aims of this study are to derive multivariate
      traits by identifying homogeneous groups of people and assigning both qualitative
      and quantitative trait scores; to assess the heritability of the derived traits;
      and to conduct both qualitative and quantitative linkage analysis on one of the
      heritable traits. METHODS: Multiple correspondence analysis, a nonparametric
      analogue of principal components analysis, was used for data reduction. Two-stage
      clustering, using both k-means and agglomerative hierarchical clustering, was
      used to cluster individuals based upon axes (factor) scores obtained from the
      data reduction. Probability of cluster membership was calculated using binary
      logistic regression. Heritability was calculated using SOLAR, which was also used
      for the quantitative trait analysis. GENEHUNTER-PLUS was used for the qualitative
      trait analysis. RESULTS: We found four phenotypically distinct groups. Membership
      in the smallest group was heritable (38%, p < 1 x 10(-6)) and had characteristics
      consistent with atherogenic dyslipidemia. We found both qualitative and
      quantitative LOD scores above 3 on chromosomes 11 and 14 (11q13, 14q23, 14q31).
      There were two Kong & Cox LOD scores above 1.0 on chromosome 6 (6p21) and
      chromosome 11 (11q23). CONCLUSION: This approach may be useful for the
      identification of genetic heterogeneity in complex phenotypes by clarifying the
      phenotype definition prior to linkage analysis. Some of our findings are in
      regions linked to elements of atherogenic dyslipidemia and related diagnoses,
      some may be novel, or may be false positives.

PMID- 14975084
TI  - Power of maximum HLOD tests to detect linkage to obesity genes.
AB  - BACKGROUND: We investigate the power of heterogeneity LOD test to detect linkage
      when a trait is determined by several major genes using Genetic Analysis Workshop
      13 simulated data. We consider three traits, two of which are disease-causing
      traits: 1) the rate of change in body mass index (BMI); and 2) the maximum BMI;
      and 3) the disease itself (hypertension). Of interest is the power of "HLOD2",
      the maximum heterogeneity LOD obtained upon maximizing over the two genetic
      models. RESULTS: Using a trait phenotype Obesity Slope, we observe that the power
      to detect the two markers closest to the two genes (S1, S2) at the 0.05 level
      using HLOD2 is 13% and 10%. The power of HLOD2 for Max BMI phenotype is 12% and
      9%. The corresponding values for the Hypertension phenotype are 8% and 6%.
      CONCLUSION: The power to detect linkage to the slope genes is quite low. But the
      power using disease-related traits as a phenotype is greater than the power using
      the disease (hypertension) phenotype.

PMID- 14975085
TI  - Comparison of longitudinal variance components and regression-based approaches
      for linkage detection on chromosome 17 for systolic blood pressure.
AB  - We compare two methods to detect genetic linkage by using serial observations of
      systolic blood pressure in pedigree data from the Framingham Heart Study focusing
      on chromosome 17. The first method is a variance components (VC) approach that
      incorporates longitudinal pedigree data, and the second method is a regression
      based approach that summarizes all longitudinal measures in one single measure.
      No evidence of linkage was found either using the VC longitudinal approach or the
      regression-based approach, except when all time points were used from Cohorts 1
      and 2 and only subjects aged 25 and 75 years were included.

PMID- 14975086
TI  - Analysis of gene x environment interactions in sibships using mixed models.
AB  - BACKGROUND: Gene x environment models are widely used to assess genetic and
      environmental risks and their association with a phenotype of interest for many
      complex diseases. Mixed generalized linear models were used to assess gene x
      environment interactions with respect to systolic blood pressure on sibships
      adjusting for repeated measures and hierarchical nesting structures. A data set
      containing 410 sibships from the Framingham Heart Study offspring cohort (part of
      the Genetic Analysis Workshop 13 data) was used for all analyses. Three mixed
      gene x environment models, all adjusting for repeated measurement and varying
      levels of nesting, were compared for precision of estimates: 1) all sibships with
      adjustment for two levels of nesting (sibs within sibships and sibs within
      pedigrees), 2) all sibships with adjustment for one level of nesting (sibs within
      sibships), and 3) 100 data sets containing random draws of one sibship per
      extended pedigree adjusting for one level of nesting. RESULTS: The main effects
      were: gender, baseline age, body mass index (BMI), hypertensive treatment,
      cigarettes per day, grams of alcohol per day, and marker GATA48G07A. The
      interaction fixed effects were: baseline age by gender, baseline age by
      cigarettes per day, baseline age by hypertensive treatment, baseline age by BMI,
      hypertensive treatment by BMI, and baseline age by marker GATA48G07A. The
      estimates for all three nesting techniques were not widely discrepant, but
      precision of estimates and determination of significant effects did change with
      the change in adjustment for nesting. CONCLUSION: Our results show the importance
      of the adjustment for all levels of hierarchical nesting of sibs in the presence
      of repeated measures.

PMID- 14975087
TI  - Multilevel modeling for the analysis of longitudinal blood pressure data in the
      Framingham Heart Study pedigrees.
AB  - BACKGROUND: The data arising from a longitudinal familial study have a complex
      correlation structure that cannot be modeled using classical methods for the
      analysis of familial data at a single time point. METHODS: To fit the
      longitudinal systolic blood pressure (SBP) pedigree data arising from the
      Framingham Heart Study, we proposed to use multilevel modeling. That approach was
      used to distinguish multiple levels of information with individual repeated
      measurements (Level 1) being made within individuals (Level 2), and individuals
      clustered within pedigrees (Level 3). Residuals from the subject-specific and
      pedigree-specific regression models were summed both for the mean SBP and slope
      of SBP change over time, in order to define two new outcomes that were then used
      in a genome-wide linkage analysis. RESULTS: Evidence for linkage for the two
      outcomes (mean SBP and slope) was found in several chromosomal regions with a
      maximum LOD score of 3.6 on chromosome 8 and 3.5 on chromosome 17 for the mean
      SBP, and 2.5 on chromosome 1 for SBP slope. However, the linkage on chromosome 8
      was only detected when the sample was restricted to subjects between age 25 and
      75 and with at least four exams (Cohort 1) or 3 exams (Cohort 2). DISCUSSION:
      Multilevel modeling is a powerful approach to detect genes involved in complex
      traits when longitudinal data are available. It allows for complex hierarchical
      data structure to be taken into account and therefore, a better partitioning of
      random within-individual variation from other sources of variability (genetic or
      nongenetic).

PMID- 14975088
TI  - Comparison of the linkage results of two phenotypic constructs from longitudinal
      data in the Framingham Heart Study: analyses on data measured at three time
      points and on the average of three measurements.
AB  - BACKGROUND: Family studies are often conducted in a cross-sectional manner
      without long-term follow-up data. The relative contribution of a gene to a
      specific trait could change over the lifetime. The Framingham Heart Study offers
      a unique opportunity to investigate potential gene x time interaction. We
      performed linkage analysis on the body mass index (BMI) measured in 1970, 1978,
      and 1986 for this project. RESULTS: We analyzed the data in two different ways:
      three genome-wide linkage analyses on each exam, and one genome-wide linkage
      analysis on the mean of the three measurements. Variance-component linkage
      analyses were performed by the SOLAR program. Genome-wide scans show consistent
      evidence of linkage of quantitative trait loci (QTLs) on chromosomes 3, 6, 9, and
      16 in three measurements with a maximum multipoint LOD score > 2.2. However, only
      chromosome 9 has a LOD score = 2.14 when the mean values were analyzed. More
      interestingly, we found potential gene x environment interactions: increasing LOD
      scores with age on chromosomes 3, 9, and 16 and decreasing LOD scores on
      chromosome 6 in the three exams. CONCLUSION: The results indicate two points: 1)
      it is possible that a gene (or genes) influencing BMI is (are) up- or down
      regulated as people aged due to aging process or changes in lifestyle,
      environments, or genetic epistasis; 2) using mean values from longitudinal data
      may reduce the power to detect linkage and may have no power to detect gene x
      time, and/or gene x gene interactions.

PMID- 14975089
TI  - Segregation and linkage analysis for longitudinal measurements of a quantitative
      trait.
AB  - We present a method for using slopes and intercepts from a linear regression of a
      quantitative trait as outcomes in segregation and linkage analyses. We apply the
      method to the analysis of longitudinal systolic blood pressure (SBP) data from
      the Framingham Heart Study. A first-stage linear model was fit to each subject's
      SBP measurements to estimate both their slope over time and an intercept, the
      latter scaled to represent the mean SBP at the average observed age (53.7 years).
      The subject-specific intercepts and slopes were then analyzed using segregation
      and linkage analysis. We describe a method for using the standard errors of the
      first-stage intercepts and slopes as weights in the genetic analyses. For the
      intercepts, we found significant evidence of a Mendelian gene in segregation
      analysis and suggestive linkage results (with LOD scores >or= 1.5) for specific
      markers on chromosomes 1, 3, 5, 9, 10, and 17. For the slopes, however, the data
      did not support a Mendelian model, and thus no formal linkage analyses were
      conducted.

PMID- 14975090
TI  - Longitudinal variance-components analysis of the Framingham Heart Study data.
AB  - The Framingham Heart Study offspring cohort, a complex data set with irregularly
      spaced longitudinal phenotype data, was made available as part of Genetic
      Analysis Workshop 13. To allow an analysis of all of the data simultaneously, a
      mixed-model- based random-regression (RR) approach was used. The RR accounted for
      the variation in genetic effects (including marker-specific quantitative trait
      locus (QTL) effects) across time by fitting polynomials of age. The use of a
      mixed model allowed both fixed (such as sex) and random (such as familial
      environment) effects to be accounted for appropriately. Using this method we
      performed a QTL analysis of all of the available adult phenotype data (26,106
      phenotypic records). In addition to RR, conventional univariate variance
      component techniques were applied. The traits of interest were BMI, HDLC, total
      cholesterol, and height. The longitudinal method allowed the characterization of
      the change in QTL effects with aging. A QTL affecting BMI was shown to act mainly
      at early ages.

PMID- 14975091
TI  - Comparison of Haseman-Elston regression analyses using single, summary, and
      longitudinal measures of systolic blood pressure.
AB  - To compare different strategies for linkage analyses of longitudinal quantitative
      trait measures, we applied the "revisited" Haseman-Elston (RHE) regression model
      (the cross product of centered sib-pair trait values is regressed on expected
      identical-by-descent allele sharing) to cross-sectional, summary, and repeated
      measurements of systolic blood pressure (SBP) values in replicate 34, randomly
      selected from the Genetic Analysis Workshop 13 simulated data. RHE linkage scans
      were performed without knowledge of the generating model using the following
      phenotypes derived from untreated SBP measurements: the first, the last, the
      mean, the ratio of the change between the first and last over time, and the
      estimated linear regression slope coefficient. Estimates of allele sharing in
      sibling pairs were obtained from the complete genotype data of Cohorts 1 and 2,
      but linkage analyses were restricted to the five visits of Cohort 2 siblings.
      Evidence for linkage was suggestive (p < 0.001) at markers neighboring SBP genes
      Gb35, Gs10, and Gs12, but weaker signals (p < 0.01) were obtained at markers
      mapping close to Gb34 and Gs11. Linkage to baseline genes Gb34 and Gb35 was best
      detected using the first SBP measurement, whereas linkage to slope genes Gs10-12
      was best detected using the last or mean SBP value. At markers on chromosomes 13
      and 21 displaying strongest linkage signals, marginal RHE-type models including
      repeated SBP measures were fit to test for overall and time-dependent genetic
      effects. These analyses assumed independent sib pairs and employed generalized
      estimating equations (GEE) with a first-order autoregressive working correlation
      structure to adjust for serial correlation present among repeated observations
      from the same sibling pair.

PMID- 14975092
TI  - Genetic linkage analysis of longitudinal hypertension phenotypes using three
      summary measures.
AB  - BACKGROUND: Longitudinal data often have multiple (repeated) measures recorded
      along a time trajectory. For example, the two cohorts from the Framingham Heart
      Study (GAW13 Problem 1) contain 21 and 5 repeated measures for hypertension
      phenotypes as well as epidemiological risk factors, respectively. Direct
      modelling of a large number of serially and biologically correlated traits in the
      context of linkage analysis can be prohibitively complex. Alternatively, we may
      consider using univariate transformation for linkage analysis of longitudinal
      repeated measures. RESULTS: We evaluated the utility of three conventional
      summary measures (mean, slope, and principal components) for genetic linkage
      analysis of longitudinal phenotypes by analyzing the chromosome 10 data of the
      Framingham Heart Study. Except for the temporal slope, all of the summary methods
      and the multivariate analysis identified the previously reported region, marker
      GATA64A09, for systolic blood pressure or high blood pressure. Further analysis
      revealed that this region may harbor gene(s) affecting human blood pressure at
      multiple stages of life. CONCLUSION: We conclude that mean and principal
      components are feasible alternatives for genetic linkage analysis of longitudinal
      phenotypes, but the slope might have a separate genetic basis from that of the
      original longitudinal phenotypes.

PMID- 14975093
TI  - Longitudinal variance components models for systolic blood pressure, fitted using
      Gibbs sampling.
AB  - This paper describes an analysis of systolic blood pressure (SBP) in the Genetic
      Analysis Workshop 13 (GAW13) simulated data. The main aim was to assess evidence
      for both general and specific genetic effects on the baseline blood pressure and
      on the rate of change (slope) of blood pressure with time. Generalized linear
      mixed models were fitted using Gibbs sampling in WinBUGS, and the additive
      polygenic random effects estimated using these models were then used as
      continuous phenotypes in a variance components linkage analysis. The first-stage
      analysis provided evidence for general genetic effects on both the baseline and
      slope of blood pressure, and the linkage analysis found evidence of several
      genes, again for both baseline and slope.

PMID- 14975094
TI  - Linkage analysis of cross-sectional and longitudinally derived phenotypic
      measures to identify loci influencing blood pressure.
AB  - BACKGROUND: The design of appropriate strategies to analyze and interpret linkage
      results for complex human diseases constitutes a challenge. Parameters such as
      power, definition of phenotype, and replicability have to be taken into account
      in order to reach meaningful conclusions. Incorporating data on repeated
      phenotypic measures may increase the power to detect linkage but requires
      sophisticated analysis methods. Using the simulated Genetic Analysis Workshop 13
      data set, we have estimated a variety of systolic blood pressure (SBP) phenotypic
      measures and examined their performance with respect to consistency among
      replicates and to true and false positive linkage signals. RESULTS: The whole
      genome scan conducted on a dichotomous hypertension phenotype indicated the
      involvement of few true loci with nominal significance and gave rise to a high
      rate of false positives. Analysis of a cross-sectional quantitative SBP measure
      performed better, although genome-wide significance was again not reached.
      Additional phenotypic measures were derived from the longitudinal data using
      random effects modelling for censored data with varying levels of covariate
      adjustment. These models provided evidence for significant linkage to most genes
      influencing SBP and produced few false positive results. Overall, replicability
      of results was poor for loci, representing weak effects. CONCLUSION:
      Longitudinally derived phenotypes performed better than cross-sectional measures
      in linkage analyses. Bearing in mind the sample design and size of these data,
      linkage results that fail to replicate should not be dismissed; instead,
      different lines of evidence derived from complementary analysis methods should be
      combined to prioritize follow up.

PMID- 14975095
TI  - Linkage analysis of longitudinal data.
AB  - BACKGROUND: We propose a statistical model for linkage analysis of the
      longitudinal data. The proposed model is a mixed model based on the new Haseman
      and Elston model and allows several random effects. Specifically, the proposed
      model includes a random effect for correlation among sib pairs having one sibling
      in common, and one for the correlation among siblings from the same parents.
      RESULTS: The proposed model was applied to the analysis of the Genetic Analysis
      Workshop 13 simulated data set for a quantitative trait of the systolic blood
      pressure. A simple independence model and two kinds of random effects models
      yielded good power for detecting linkage for these data sets, while the random
      effects models performed slightly better than the independence model. Both random
      effects models showed similar performance. CONCLUSIONS: The proposed models seem
      not only quite useful in detecting linkage with the longitudinal data for the
      trait but also quite flexible. They can handle a wide class of correlation
      structures. Models with a more general class of covariance structure are
      desirable.

PMID- 14975096
TI  - Power of linkage analysis using traits generated from simulated longitudinal data
      of the Framingham Heart Study.
AB  - The Framingham Heart Study is a very successful longitudinal research for
      cardiovascular diseases. The completion of a 10-cM genome scan in Framingham
      families provided an opportunity to evaluate linkage using longitudinal data.
      Several descriptive traits based on simulated longitudinal data from the Genetic
      Analysis Workshop 13 (GAW13) were generated, and linkage analyses were performed
      for these traits. We compared the power of detecting linkage for baseline and
      slope genes in the simulated data of GAW13 using these traits. We found that
      using longitudinal traits based on multiple follow-ups may not be more powerful
      than using cross-sectional traits for genetic linkage analysis.

PMID- 14975097
TI  - Genetic analyses of longitudinal phenotype data: a comparison of univariate
      methods and a multivariate approach.
AB  - BACKGROUND: We explored three approaches to heritability and linkage analyses of
      longitudinal total cholesterol levels (CHOL) in the Genetic Analysis Workshop 13
      simulated data without knowing the answers. The first two were univariate
      approaches and used 1) baseline measure at exam one or 2) summary measures such
      as mean and slope from multiple exams. The third method was a multivariate
      approach that directly models multiple measurements on a subject. A variance
      components model (SOLAR) was employed in the univariate approaches. A mixed
      regression model with polynomials was employed in the multivariate approach and
      implemented in SAS/IML. RESULTS: Using the baseline measure at exam 1, we
      detected all baseline or slope genes contributing a substantial amount (0.08) of
      variance (LOD > 3). Compared to the baseline measure, the mean measures yielded
      slightly higher LOD at the slope genes, and a lower LOD at the baseline genes.
      The slope measure produced a somewhat lower LOD for the slope gene than did the
      mean measure. Descriptive information on the pattern of changes in gene effects
      with age was estimated for three linked loci by the third approach. CONCLUSION:
      We found simple univariate methods may be effective to detect genes affecting
      longitudinal phenotypes but may not fully reveal temporal trends in gene effects.
      The relative efficiency of the univariate methods to detect genes depends heavily
      on the underlying model. Compared with the univariate approaches, the
      multivariate approach provided more information on temporal trends in gene
      effects at the cost of more complicated modelling and more intense computations.

PMID- 14975098
TI  - Consistency of linkage results across exams and methods in the Framingham Heart
      Study.
AB  - BACKGROUND: The repeated measures in the Framingham Heart Study in the Genetic
      Analysis Workshop 13 data set allow us to test for consistency of linkage results
      within a study across time. We compared regression-based linkage to variance
      components linkage across time for six quantitative traits in the real data.
      RESULTS: The variance components approach found 11 significant linkages, the
      regression-based approach found 4. There was only one region that overlapped.
      Consistency between exams generally decreased as the time interval between exams
      increased. The regression-based approach showed higher consistency in linkage
      results across exams. CONCLUSION: The low consistency between exams and between
      methods may help explain the lack of replication between studies in this field.

PMID- 14975099
TI  - Age-stratified QTL genome scan analyses for anthropometric measures.
AB  - With the availability of longitudinal data, age-specific (stratified) or age
      adjusted genetic analyses have the potential to localize different putative trait
      influencing loci. If age does not influence the locus-specific penetrance
      function within the range examined, age-stratified analyses will tend to yield
      comparable results for an individual trait. However, age-stratified results
      should vary across age strata when the locus-specific penetrance function is age
      dependent. In this paper, age-stratified and age-adjusted quantitative trait loci
      (QTL) linkage analyses were contrasted for height, weight, body mass index (BMI),
      and systolic blood pressure on a subset of the Framingham Heart Study. The strata
      comprised individuals with data present in each of three age groups: 31-49, 50
      60, 61-79. Genome-wide QTL analyses were performed using SOLAR. Over all ages, a
      linkage signal for height was detected on chromosome 14q11.2 near marker
      GATA74E02A (LOD for ages 31-49 = 2.38, LOD for ages 50-60 = 1.84, LOD for ages 61
      79 = 2.45). Evidence of linkage to BMI in the 31-49 age group was found on
      chromosome 3q22 (GATA3C02, LOD = 2.89, p = 0.0003) at the same location as the
      signal for weight (LOD = 3.10, p = 0.0002). Linkage was also supported on
      chromosome 1p22.1 for BMI (LOD = 2.21, p = 0.0014) and weight (LOD = 2.47, p =
      0.0007) in the 31-49 age group. Our age-stratified results suggest that QTL that
      are expressed over long periods of time and affecting multiple, correlated traits
      may be identified using genome scan and variance-component methodology to help
      detect early and/or late gene expression.

PMID- 14975100
TI  - Age-stratified heritability estimation in the Framingham Heart Study families.
AB  - The Framingham Heart Study provides a unique source of longitudinal family data
      related to CVD risk factors. Age-stratified heritability estimates were obtained
      over three age groups (31-49 years, 50-60 years, and 61-79 years), reflecting the
      longitudinal nature of the data, for four quantitative traits. Age-adjusted
      heritability estimates were obtained at a single common time point for the same
      four quantitative traits. The importance of these groups is that they consist of
      the same individuals. The highest age-stratified heritability estimate (h2 = 0.88
      (+/- 0.06)) was for height in the model adjusting for gender over all three age
      groups. SBP gave the lowest heritability estimate (h2 = 0.15 (+/- 0.11)) for the
      70 age group in the model adjusting for gender, height, BMI, smoker, and drinker.
      BMI had slightly higher estimates (h2 = 0.64 (+/- 0.11)) in the 40 age group than
      previously published. The highest age-adjusted heritability estimate (h2 = 0.90
      (+/- 0.06)) was for height in the model adjusting for gender. SBP gave the lowest
      heritability estimate (h2 = 0.38 (+/- 0.09)) for unadjusted model. These results
      indicate that some common, complex traits may vary little in their genetic
      architecture over time and suggest that a common set of genes may be contributing
      to observed variation for these longitudinally collected phenotypes.

PMID- 14975101
TI  - Sibling recurrence risk ratio analysis of the metabolic syndrome and its
      components over time.
AB  - BACKGROUND: The purpose of this study was to estimate both cross-sectional
      sibling recurrence risk ratio (lambdas) and lifetime lambdas for the metabolic
      syndrome and its individual components over time among sibships in the
      prospectively followed-up cohorts provided by the Genetic Analysis Workshop 13.
      Five measures included in the operational criteria of the metabolic syndrome by
      the Adult Treatment Panel III were examined. A method for estimating sibling
      recurrence risk with correction for complete ascertainment was used to estimate
      the numerator, and the prevalence in the whole cohort was used as the denominator
      of lambdas. RESULTS: Considerable variability in the lambdas was found in terms
      of different time-points for the cross-sectional definition, the times of
      fulfilling the criterion for lifetime definition, and different components.
      Obesity and hyperglycemia had the highest cross-sectional lambdas of the five
      components. Both components also had the largest slopes in the linear trend of
      the lifetime lambdas. However, the magnitudes of the lifetime lambdas were
      similar to that of the mean cross-sectional lambdas, which were <2. The results
      of nonparametric linkage analysis showed only suggestive evidence of linkage
      between one marker and lifetime diagnosis of low high-density lipoprotein
      cholesterol and metabolic syndrome, respectively. CONCLUSION: The lambdas of the
      metabolic syndrome and its components varies substantially across time, and the
      lambdas of lifetime diagnosis was not necessarily larger than that of a cross
      sectional diagnosis. The magnitude of lambdas does not predict well the maximum
      LOD score of linkage analysis.

PMID- 14975102
TI  - Strategy and model building in the fourth dimension: a null model for genotype x
      age interaction as a Gaussian stationary stochastic process.
AB  - BACKGROUND: Using univariate and multivariate variance components linkage
      analysis methods, we studied possible genotype x age interaction in
      cardiovascular phenotypes related to the aging process from the Framingham Heart
      Study. RESULTS: We found evidence for genotype x age interaction for fasting
      glucose and systolic blood pressure. CONCLUSIONS: There is polygenic genotype x
      age interaction for fasting glucose and systolic blood pressure and quantitative
      trait locus x age interaction for a linkage signal for systolic blood pressure
      phenotypes located on chromosome 17 at 67 cM.

PMID- 14975103
TI  - Genome-wide linkage analysis using cross-sectional and longitudinal traits for
      body mass index in a subsample of the Framingham Heart Study.
AB  - To evaluate linkage evidence for body mass index (BMI) using both cross-sectional
      and longitudinal data, we performed genome-wide multipoint linkage analyses on
      subjects who had complete data at four selected time points (initial, 8th, 12th,
      and 16th year following the initial visit) from the Framingham Heart Study. The
      cross-sectional measures included BMI at each of the four selected time points
      and the longitudinal measure was the within-subject mean of BMI at the above four
      time points. Using the variance components method, we consistently observed the
      maximum LOD score out of the genome scan using BMI at each time point and the
      mean of BMI between 049xd2 and GATA71H05 on chromosome 16. The highest LOD score
      (3.0) was at time point 1, while the lowest (1.9) was at time point 4. We also
      observed other suggestive linkages on chromosome 6, 10, and 18 at time point 1
      only. The longitudinal measure we studied (mean of BMI) did not provide greater
      power to identify a positive linkage than some of the cross-sectional measures
      (e.g., time point 1). The changing of linkage evidence over time provided some
      insights on the variation of genetic effect on BMI with aging. There may be a QTL
      on chromosome 16 that contributes to BMI and this locus, and maybe others, is
      more likely to affect BMI during early adulthood.

PMID- 14975104
TI  - Comparison of year-of-exam- and age-matched estimates of heritability in the
      Framingham Heart Study data.
AB  - Several different approaches can be used to examine generational and temporal
      trends in family studies. The measurement of offspring and parents can be made
      over a short period of time with parents and offspring having quite different
      ages, or measurements can be made at the same ages but with decades between
      parent and offspring measures. A third approach, used in the Framingham Heart
      Study, has repeated examinations across a broad range of age and time, and
      provides a unique opportunity to compare these approaches. Parents and offspring
      were matched both on (year of exam) and on age. Heritability estimates for
      systolic blood pressure, body mass index, height, weight, cholesterol, and
      glucose were obtained by regressing offspring on midparent values with and
      without adjustment for age. Higher estimates of heritability were obtained for
      age-matched than for year-of-exam-matched data for all traits considered. For
      most traits, estimates of the heritability of the change over time (slope) of the
      trait were near zero. These results suggest that the optimal design to identify
      genetic effects in traits with large age-related effects may be to measure
      parents and offspring at similar ages and not to rely on age-adjustment or
      longitudinal measures to account for these temporal effects.

PMID- 14975105
TI  - Lack of reproducibility of linkage results in serially measured blood pressure
      data.
AB  - BACKGROUND: Using the longitudinal Framingham Heart Study data on blood pressure,
      we analyzed the reproducibility of linkage measures from serial cross-sectional
      surveys of a defined population by performing genome-wide model-free linkage
      analyses to systolic blood pressure (SBP) and history of hypertension (HTN)
      measured at five separate time points. RESULTS: The heritability of SBP was
      relatively stable over time, ranging from 11.6 to 23.5% (coefficient of variation
      = 25.7%). However, the variability in linkage results was much greater. The
      average correlation in LOD scores at any pair of time points was 0.46 for HTN
      (NPL All LOD) and 0.17 for SBP (Variance Components LOD). No evidence of
      reproducible linkage results was found, with a mean kappa of 0.02 for linkage to
      HTN and -0.03 for SBP linkage. At loci with potential evidence for linkage (LOD >
      1.0 at one or more time points), the correlation was even lower. The coefficient
      of variation at loci with potential evidence of linkage was 126% for HTN and 135%
      for SBP. None of 15 chromosomal regions for HTN and only one of 28 regions for
      SBP with potential evidence for linkage had a LOD > 1.0 at more than two of the
      five time points. CONCLUSION: These data suggest that, although heritability
      estimates at different time points are relatively robust, the reproducibility of
      linkage results in serial cross-sectional samples of a geographically defined
      population at successive time points is poor. This may explain in part the
      difficulty encountered in replicating linkage studies of complex phenotypes.

PMID- 14975106
TI  - Stability of exploratory multivariate data modeling in longitudinal data.
AB  - Exploratory data-driven multivariate analysis provides a means of investigating
      underlying structure in complex data. To explore the stability of multivariate
      data modeling, we have applied a common method of multivariate modeling (factor
      analysis) to the Genetic Analysis Workshop 13 (GAW13) Framingham Heart Study
      data. Given the longitudinal nature of the data, multivariate models were
      generated independently for a number of different time points (corresponding to
      cross-sectional clinic visits for the two cohorts), and compared. In addition,
      each multivariate model was used to generate factor scores, which were then used
      as a quantitative trait in variance component-based linkage analysis to
      investigate the stability of linkage signals over time. We found surprisingly
      good correlation between factor models (i.e., predicted factor structures),
      maximum LOD scores, and locations of maximum LOD scores (0.81< rho <0.94 for
      factor scores; rho >0.99 for peak locations; and 0.67< rho <0.93 for peak LOD
      scores). Furthermore, the regions implicated by linkage analysis with these
      factor scores have also been observed in other studies, further validating our
      exploratory modeling.

PMID- 14975107
TI  - Bootstrap calibration of TRANSMIT for informative missingness of parental
      genotype data.
AB  - Informative missingness of parental genotype data occurs when the genotype of a
      parent influences the probability of the parent's genotype data being observed.
      Informative missingness can occur in a number of plausible ways and can affect
      both the validity and power of procedures that assume the data are missing at
      random (MAR). We propose a bootstrap calibration of MAR procedures to account for
      informative missingness and apply our methodology to refine the approach
      implemented in the TRANSMIT program. We illustrate this approach by applying it
      to data on hypertensive probands and their parents who participated in the
      Framingham Heart Study.

PMID- 14975108
TI  - An examination of the genotyping error detection function of SIMWALK2.
AB  - This investigation was undertaken to assess the sensitivity and specificity of
      the genotyping error detection function of the computer program SIMWALK2. We
      chose to examine chromosome 22, which had 7 microsatellite markers, from a single
      simulated replicate (330 pedigrees with a pattern of missing genotype data
      similar to the Framingham families). We created genotype errors at five overall
      frequencies (0.0, 0.025, 0.050, 0.075, and 0.100) and applied SIMWALK2 to each of
      these five data sets, respectively assuming that the total error rate (specified
      in the program), was at each of these same five levels. In this data set, up to
      an assumed error rate of 10%, only 50% of the Mendelian-consistent mistypings
      were found under any level of true errors. And since as many as 70% of the errors
      detected were false-positives, blanking suspect genotypes (at any error
      probability) will result in a reduction of statistical power due to the
      concomitant blanking of correctly typed alleles. This work supports the
      conclusion that allowing for genotyping errors within likelihood calculations
      during statistical analysis may be preferable to choosing an arbitrary cut-off.

PMID- 14975109
TI  - Pedigree and genotype errors in the Framingham Heart Study.
AB  - The pedigree and genotype data from the Framingham Heart Study were examined for
      errors. Errors in 21 of 329 pedigrees were detected with the program PREST, and
      of these the errors in 16 pedigrees were resolved. Genotyping errors were then
      detected with SIMWALK2. Five Mendelian errors were found following the pedigree
      corrections. Double-recombinant errors were more common, with 142 being detected
      at mistyping probabilities of 0.25 or greater.

PMID- 14975110
TI  - Imputation methods for missing data for polygenic models.
AB  - Methods to handle missing data have been an area of statistical research for many
      years. Little has been done within the context of pedigree analysis. In this
      paper we present two methods for imputing missing data for polygenic models using
      family data. The imputation schemes take into account familial relationships and
      use the observed familial information for the imputation. A traditional multiple
      imputation approach and multiple imputation or data augmentation approach within
      a Gibbs sampler for the handling of missing data for a polygenic model are
      presented.We used both the Genetic Analysis Workshop 13 simulated missing
      phenotype and the complete phenotype data sets as the means to illustrate the two
      methods. We looked at the phenotypic trait systolic blood pressure and the
      covariate gender at time point 11 (1970) for Cohort 1 and time point 1 (1971) for
      Cohort 2. Comparing the results for three replicates of complete and missing data
      incorporating multiple imputation, we find that multiple imputation via a Gibbs
      sampler produces more accurate results. Thus, we recommend the Gibbs sampler for
      imputation purposes because of the ease with which it can be extended to more
      complicated models, the consistency of the results, and the accountability of the
      variation due to imputation.

PMID- 14975111
TI  - Multiple imputation methods for longitudinal blood pressure measurements from the
      Framingham Heart Study.
AB  - Missing data are a great concern in longitudinal studies, because few subjects
      will have complete data and missingness could be an indicator of an adverse
      outcome. Analyses that exclude potentially informative observations due to
      missing data can be inefficient or biased. To assess the extent of these problems
      in the context of genetic analyses, we compared case-wise deletion to two
      multiple imputation methods available in the popular SAS package, the propensity
      score and regression methods. For both the real and simulated data sets, the
      propensity score and regression methods produced results similar to case-wise
      deletion. However, for the simulated data, the estimates of heritability for case
      wise deletion and the two multiple imputation methods were much lower than for
      the complete data. This suggests that if missingness patterns are correlated
      within families, then imputation methods that do not allow this correlation can
      yield biased results.

PMID- 14975112
TI  - Comparison of missing data approaches in linkage analysis.
AB  - BACKGROUND: Observational cohort studies have been little used in linkage
      analyses due to their general lack of large, disease-specific pedigrees.
      Nevertheless, the longitudinal nature of such studies makes them potentially
      valuable for assessing the linkage between genotypes and temporal trends in
      phenotypes. The repeated phenotype measures in cohort studies (i.e., across
      time), however, can have extensive missing information. Existing methods for
      handling missing data in observational studies may decrease efficiency, introduce
      biases, and give spurious results. The impact of such methods when undertaking
      linkage analysis of cohort studies is unclear. Therefore, we compare here six
      methods of imputing missing repeated phenotypes on results from genome-wide
      linkage analyses of four quantitative traits from the Framingham Heart Study
      cohort. RESULTS: We found that simply deleting observations with missing values
      gave many more nominally statistically significant linkages than the other five
      approaches. Among the latter, those with similar underlying methodology (i.e.,
      imputation- versus model-based) gave the most consistent results, although some
      discrepancies remained. CONCLUSION: Different methods for addressing missing
      values in linkage analyses of cohort studies can give substantially diverse
      results, and must be carefully considered to protect against biases and spurious
      findings.

PMID- 14975113
TI  - Interaction of gender and body mass index (BMI) reveals evidence of linkage for
      hypertension in the Framingham Heart Study.
AB  - BACKGROUND: Genetic heterogeneity and complex biologic mechanisms of blood
      pressure regulation pose significant challenges to the identification of
      susceptibility loci influencing hypertension. Previous linkage studies have
      reported regions of interest, but lack consistency across studies. Incorporation
      of covariates, in particular the interaction between two independent risk factors
      (gender and BMI) greatly improved our ability to detect linkage. RESULTS: We
      report a highly significant signal for linkage to chromosome 2p, a region that
      has been implicated in previous linkage studies, along with several suggestive
      linkage regions. CONCLUSION: We demonstrate the importance of including
      covariates in the linkage analysis when the phenotype is complex.

PMID- 14975114
TI  - Comparison of significance level at the true location using two linkage
      approaches: LODPAL and GENEFINDER.
AB  - BACKGROUND: We compare two new software packages for linkage analysis, LODPAL and
      GENEFINDER. Both allow for covariate adjustment. Replicates 1 to 3 of Genetic
      Analysis Workshop 13 simulated data sets were used for the analyses. We described
      the results of searching for evidence of loci contributing to a simulated
      quantitative trait related to systolic blood pressure (SBP). Individuals with SBP
      greater than 130 mm Hg were defined as affected individuals, and all others as
      unaffected. Total cholesterol was treated as a covariate. RESULTS: Using LODPAL,
      the power of detecting one of the three major genes related to SBP is 44.4% when
      a LOD score of 1 is used as the cut-off point. The power of GENEFINDER is lower
      than that of LODPAL. It is 22.2%. CONCLUSIONS: Based on the limited comparison,
      LODPAL provided the more reasonable power to detect linkage compared to
      GENEFINDER. After adjusting for the total cholesterol covariate, the current
      version of both programs appeared to give a high number of false positives.

PMID- 14975115
TI  - Genome-wide scan on plasma triglyceride and high density lipoprotein cholesterol
      levels, accounting for the effects of correlated quantitative phenotypes.
AB  - BACKGROUND: Plasma triglyceride and high density lipoprotein cholesterol levels
      are inversely correlated and both are genetically related. Two correlated traits
      may be influenced both by shared and unshared genes. The power to detect unshared
      trait-specific genes may be increased by incorporating correlated traits as
      covariates. The power to localize the shared genes may be improved by bivariate
      analysis. Univariate genome scans were carried out on triglyceride (high density
      lipoprotein cholesterol) with and without using high density lipoprotein
      cholesterol (triglyceride) as a covariate, and bivariate linkage analysis on
      triglyceride and high density lipoprotein cholesterol using the 330 Framingham
      pedigrees of the Genetic Analysis Workshop 13 data. The results of five genome
      scans were compared to determine the chromosomal regions which may harbor the
      genes influencing variation specific to triglycerides, specific to high density
      lipoprotein cholesterol, or the covariation of both triglyceride and high density
      lipoprotein cholesterol. RESULTS: The results of our five genome scans identified
      some chromosomal regions with possible quantitative trait loci (QTL) that may
      specifically influence one trait, such as the regions on chromosome 1 (at 1 cM
      near marker 280we5), on high density lipoprotein cholesterol, or control the
      covariation of both traits, such as the regions on chromosome 7 (at 169 cM near
      marker GATA30D09), chromosome 12 (at 3 cM near marker GATA4H03), chromosome 20
      (at 49 cM near marker GATA29F06), chromosome 2 (at 146 cM near marker GATA8H05),
      and chromosome 6 (at 148 cM near marker GATA184A08) on triglyceride and high
      density lipoprotein cholesterol. The one on chromosome 6 had a LOD score of 3.1
      with the bivariate linkage analysis. CONCLUSION: There is strong evidence for a
      QTL on chromosome 6 near marker GATA184A08 appearing to influence the variation
      of high density lipoprotein cholesterol and triglycerides in the Framingham
      population.

PMID- 14975116
TI  - Transmission ratio distortion in families from the Framingham Heart Study.
AB  - BACKGROUND: One implicit assumption in most linkage analysis is that live-born
      siblings unselected for a phenotype do not share alleles greater than the
      Mendelian expectation at any particular locus. However, since most families are
      recruited for genetic studies because of the presence of disease, there is little
      data available to confirm that this is the case. We hypothesized that loci that
      behave in a non-Mendelian fashion could be identified using genotype data from
      the Framingham Heart Study families. We tested the hypothesis that live-born
      sibs, either stratified by or irrespective of gender, demonstrate excess sharing
      of alleles on the autosomes, i.e., transmission ratio distortion. Multipoint
      linkage analysis of siblings either according to gender or not was performed
      using an allele-sharing method. Such observations may have implications for the
      mapping of loci for complex disease and quantitative traits in human pedigrees.
      RESULTS: No results that reached genome-wide significance were observed. However,
      four regions demonstrated excess sharing of alleles at p < 0.002 when sibships
      were stratified by gender-three of which were present in males. Of note, a female
      specific locus co-localized with region that is linked to mean systolic blood
      pressure in the same families. In addition, three other regions demonstrated
      excess sharing of alleles in sibships irrespective of gender, including a region
      on chromosome 10p14-p15 (p = 7.5 x 10(-4)). CONCLUSION: Although no loci meeting
      genome-wide significance were detected to demonstrate transmission ratio
      distortion, loci with suggestive evidence for linkage were detected. These may
      have implications for the mapping of susceptibility loci for complex disease in
      human pedigrees.

PMID- 14975117
TI  - Susceptibility scoring in family-based association testing.
AB  - BACKGROUND: Family-based association testing is an important part of genetic
      epidemiology. Tests are available to include multiple siblings, unaffected
      offspring, and to adjust for environmental covariates. We explore a
      susceptibility residual method of adjustment for covariates. RESULTS: Through
      simulation, we show that environmental adjustments that down-weight persons who
      are "destined" to be affected decrease the power to detect genetic association.
      We used the residual adjusted method on the Framingham Heart Study offspring
      data, provided for Genetic Analysis Workshop 13, and got mixed results.
      CONCLUSION: When the genetic effect and environmental effects are independent, a
      susceptibility residual method of adjustment for environmental covariates reduces
      the power of the association test. Further study is necessary to determine if
      residual adjustment is appropriate in more complex disease models.

PMID- 14975118
TI  - Adjusting for covariates on a slippery slope: linkage analysis of change over
      time.
AB  - BACKGROUND: We analyzed the Genetic Analysis Workshop 13 (GAW13) simulated data
      to contrast and compare different methods for the genetic linkage analysis of
      hypertension and change in blood pressure over time. We also examined methods for
      incorporating covariates into the linkage analysis. We used methods for
      quantitative trait loci (QTL) linkage analysis with and without covariates and
      affected sib-pair (ASP) analysis of hypertension followed by ordered subset
      analysis (OSA), using variables associated with change in blood pressure over
      time. RESULTS: Four of the five baseline genes and one of the three slope genes
      were not detected by any method using conventional criteria. OSA detected
      baseline gene b35 on chromosome 13 when using the slope in blood pressure to
      adjust for change over time. Slope gene s10 was detected by the ASP analysis and
      slope gene s11 was detected by QTL linkage analysis as well as by OSA analysis.
      Analysis of null chromosomes, i.e., chromosomes without genes, did not reveal
      significant increases in type I error. However, there were a number of genes
      indirectly related to blood pressure detected by a variety of methods.
      CONCLUSIONS: We noted that there is no obvious first choice of analysis software
      for analyzing a complicated model, such as the one underlying the GAW13 simulated
      data. Inclusion of covariates and longitudinal data can improve localization of
      genes for complex traits but it is not always clear how best to do this. It
      remains a worthwhile task to apply several different approaches since one method
      is not always the best.

PMID- 14975119
TI  - A statistical method for adjusting covariates in linkage analysis with sib pairs.
AB  - BACKGROUND: We propose a statistical method that includes the use of longitudinal
      regression models and estimation procedures for adjusting for covariate effects
      in applying the Haseman-Elston (HE) method for linkage analysis. Our methodology,
      which uses the covariate adjusted trait, contains three steps: a) modelling the
      covariate-adjusted population means of quantitative traits through regression; b)
      estimating the value of covariate-adjusted quantitative traits; and c) evaluating
      the linkage between the adjusted trait values and the markers based on alleles
      shared identically by descent. RESULTS: We applied our adjusted HE method and the
      standard HE method in S.A.G.E. to the sib-pair subset of the Framingham Heart
      Study distributed by Genetic Analysis Workshop 13 with systolic blood pressure as
      the quantitative trait. Both methods gave similar patterns for the LOD scores,
      and exhibited highest multipoint LOD scores near location 70 cM of chromosome 12.
      CONCLUSION: The adjusted HE method has two major advantages over the standard HE
      method used in S.A.G.E.: a) it has the capability to handle longitudinal data; b)
      it provides a more natural approach for adjusting the repeatedly measured
      covariates from each subject.

PMID- 14975120
TI  - Evidence for bivariate linkage of obesity and HDL-C levels in the Framingham
      Heart Study.
AB  - BACKGROUND: Epidemiological studies have indicated that obesity and low high
      density lipoprotein (HDL) levels are strong cardiovascular risk factors, and that
      these traits are inversely correlated. Despite the belief that these traits are
      correlated in part due to pleiotropy, knowledge on specific genes commonly
      affecting obesity and dyslipidemia is very limited. To address this issue, we
      first conducted univariate multipoint linkage analysis for body mass index (BMI)
      and HDL-C to identify loci influencing variation in these phenotypes using
      Framingham Heart Study data relating to 1702 subjects distributed across 330
      pedigrees. Subsequently, we performed bivariate multipoint linkage analysis to
      detect common loci influencing covariation between these two traits. RESULTS: We
      scanned the genome and identified a major locus near marker D6S1009 influencing
      variation in BMI (LOD = 3.9) using the program SOLAR. We also identified a major
      locus for HDL-C near marker D2S1334 on chromosome 2 (LOD = 3.5) and another
      region near marker D6S1009 on chromosome 6 with suggestive evidence for linkage
      (LOD = 2.7). Since these two phenotypes have been independently mapped to the
      same region on chromosome 6q, we used the bivariate multipoint linkage approach
      using SOLAR. The bivariate linkage analysis of BMI and HDL-C implicated the
      genetic region near marker D6S1009 as harboring a major gene commonly influencing
      these phenotypes (bivariate LOD = 6.2; LODeq = 5.5) and appears to improve power
      to map the correlated traits to a region, precisely. CONCLUSIONS: We found
      substantial evidence for a quantitative trait locus with pleiotropic effects,
      which appears to influence both BMI and HDL-C phenotypes in the Framingham data.

PMID- 14975121
TI  - Exploring pleiotropy using principal components.
AB  - A standard multivariate principal components (PCs) method was utilized to
      identify clusters of variables that may be controlled by a common gene or genes
      (pleiotropy). Heritability estimates were obtained and linkage analyses performed
      on six individual traits (total cholesterol (Chol), high and low density
      lipoproteins, triglycerides (TG), body mass index (BMI), and systolic blood
      pressure (SBP)) and on each PC to compare our ability to identify major gene
      effects. Using the simulated data from Genetic Analysis Workshop 13 (Cohort 1 and
      2 data for year 11), the quantitative traits were first adjusted for age, sex,
      and smoking (cigarettes per day). Adjusted variables were standardized and PCs
      calculated followed by orthogonal transformation (varimax rotation). Rotated PCs
      were then subjected to heritability and quantitative multipoint linkage analysis.
      The first three PCs explained 73% of the total phenotypic variance. Heritability
      estimates were above 0.60 for all three PCs. We performed linkage analyses on the
      PCs as well as the individual traits. The majority of pleiotropic and trait
      specific genes were not identified. Standard PCs analysis methods did not
      facilitate the identification of pleiotropic genes affecting the six traits
      examined in the simulated data set. In addition, genes contributing 20% of the
      variance in traits with over 0.60 heritability estimates could not be identified
      in this simulated data set using traditional quantitative trait linkage analyses.
      Lack of identification of pleiotropic and trait-specific genes in some cases may
      reflect their low contribution to the traits/PCs examined or more importantly,
      characteristics of the sample group analyzed, and not simply a failure of the PC
      approach itself.

PMID- 14975122
TI  - Pleiotropic effects on cardiovascular risk factors within and between the fourth
      and sixth decades of life: implications for genotype x age interactions.
AB  - We used an approach for detecting genotype x environment interactions to detect
      and characterize genotype x age interaction in longitudinal measures of three
      well known cardiovascular risk factors: total plasma cholesterol (TC), systolic
      blood pressure (SBP), and body weight (Wgt). Our objectives were to determine if
      the same gene or suite of genes influences quantitative variation in each of
      these phenotypes in the 4th and 6th decades of life, to assess the impact of
      additive gene effects in these two decades, and to evaluate the stability of
      pleiotropic relationships among these phenotypes. Using the Framingham Heart
      Study data, we constructed two cross-sectional samples comprising individuals on
      whom these phenotypes were measured at ages 30-39 years (Original Cohort: exam 1,
      Offspring Cohort: exam 2) and at ages 50-59 years (Original Cohort: exam 11,
      Offspring Cohort: exam 5). We also constructed a longitudinal sample from the
      cross-sectional sample members for whom measures on these traits were available
      at both ages (i.e., 4th and 6th decades of life). Patterns of pleiotropy,
      inferred from genetic correlations between traits, differ between the two age
      classes. Further, additive genetic variance in SBP during the 4th decade of life
      is attributable to a different gene or suite of genes than during the 6th. The
      magnitude of the effect increases for SBP. Variation in TC and Wgt appear to be
      influenced by the same gene or genes in both decades. The magnitude of the effect
      is stable for TC, but increases dramatically with age for Wgt.

PMID- 14975123
TI  - Multivariate variance-components analysis of longitudinal blood pressure
      measurements from the Framingham Heart Study.
AB  - Multivariate variance-components analysis provides several advantages over
      univariate analysis when studying correlated traits. It can test for pleiotropy
      or (in the longitudinal context) gene x age interaction. It can also have more
      power than univariate analyses to detect a quantitative trait locus influencing
      several traits. We apply multivariate variance components to longitudinal
      systolic blood pressure data from the Framingham Heart Study. We find evidence
      for a polygenic influence on blood pressure (heritabilities at different ages
      range from 27% to 38%). Tests based on a factor-analytic parameterization of the
      polygenic variance find significant (p < 2 x 10(-3)) evidence that different
      genes affect blood pressure at different ages. Still, estimates for the
      proportion of polygenic variance due to shared genes ran as high as 85% for some
      trait pairs. Univariate and multivariate linkage analyses replicate previous
      linkage results on chromosome 17 (maximum LOD scores of 2.2 and 2.4,
      respectively). In this study, multivariate analysis provides no increase in
      power; this is likely due to the strong positive correlation in systolic blood
      pressure measured at different ages.

PMID- 14975124
TI  - Genetic analysis of common factors underlying cardiovascular disease-related
      traits.
AB  - BACKGROUND: Cardiovascular disease-related traits, such as body mass index (BMI),
      systolic blood pressure (SBP), triglycerides (TG), total cholesterol (TC), high
      density lipoprotein cholesterol (HDL), and glucose levels (GLUC), have moderate
      to high correlations with each other. We hypothesized that there might be some
      common factors underlying the correlations of these traits, and attempted to
      identify these factors and their genetic structures. Cross-sectional measurements
      from the 330 extended Framingham Heart Study families were used in this study.
      Principal component factor analysis was applied to obtain the factors that were
      then analyzed using variance components linkage analysis. RESULTS: With the above
      six traits three factors were generated: BMI-SBP-GLUC, HDL-TG, and TC-TG. The
      heritabilities for these factors were 32%, 45%, and 49%, respectively. Comparing
      the linkage results of the factors with the results of their component traits,
      evidence for linkage was observed for the TC-TG factor to a locus on chromosome
      2p23 with a two-point LOD score 2.73 (marker GATA8F07) and a multipoint LOD score
      1.81 (at 54 cM), while the LOD scores for TC and TG did not exceed 1 at this
      region. CONCLUSION: Our analysis showed a locus on chromosome 2 might have a
      pleiotropic effect on the cardiovascular disease-related traits TC and TG.

PMID- 14975125
TI  - Localization of genes involved in the metabolic syndrome using multivariate
      linkage analysis.
AB  - There are no well accepted criteria for the diagnosis of the metabolic syndrome.
      However, the metabolic syndrome is identified clinically by the presence of three
      or more of these five variables: larger waist circumference, higher triglyceride
      levels, lower HDL-cholesterol concentrations, hypertension, and impaired fasting
      glucose. We use sets of two or three variables, which are available in the
      Framingham Heart Study data set, to localize genes responsible for this syndrome
      using multivariate quantitative linkage analysis. This analysis demonstrates the
      applicability of using multivariate linkage analysis and how its use increases
      the power to detect linkage when genes are involved in the same disease
      mechanism.

PMID- 14975126
TI  - Identification of genes for complex disease using longitudinal phenotypes.
AB  - Using the simulated data set from Genetic Analysis Workshop 13, we explored the
      advantages of using longitudinal data in genetic analyses. The weighted average
      of the longitudinal data for each of seven quantitative phenotypes were computed
      and analyzed. Genome screen results were then compared for these longitudinal
      phenotypes and the results obtained using two cross-sectional designs: data
      collected near a single age (45 years) and data collected at a single time point.
      Significant linkage was obtained for nine regions (LOD scores ranging from 5.5 to
      34.6) for six of the phenotypes. Using cross-sectional data, LOD scores were
      slightly lower for the same chromosomal regions, with two regions becoming
      nonsignificant and one additional region being identified. The magnitude of the
      LOD score was highly correlated with the heritability of each phenotype as well
      as the proportion of phenotypic variance due to that locus. There were no false
      positive linkage results using the longitudinal data and three false-positive
      findings using the cross-sectional data. The three false positive results appear
      to be due to the kurtosis in the trait distribution, even after removing extreme
      outliers. Our analyses demonstrated that the use of simple longitudinal
      phenotypes was a powerful means to detect genes of major to moderate effect on
      trait variability. In only one instance was the power and heritability of the
      trait increased by using data from one examination. Power to detect linkage can
      be improved by identifying the most heritable phenotype, ensuring normality of
      the trait distribution and maximizing the information utilized through novel
      longitudinal designs for genetic analysis.

PMID- 14975127
TI  - Similarity by state/descent and genetic vector spaces: analysis of a longitudinal
      family study.
AB  - Using the genome-wide screening data of the Framingham Heart Study (394 nuclear
      families, 1328 genotyped subjects, 397 marker loci) we have quantified the
      underlying genetic diversity through high-dimensional genetic feature vectors and
      constructed a genetic vector space for the analysis of population substructure.
      Adaptive clustering procedures led to three major subgroups that were regarded as
      being related to "biological" ethnicity and that included more than 70% of the
      subjects. Based on these subgroups we addressed the question of ethnicity-related
      and ethnicity-independent risk factors for coronary heart disease (CHD). To this
      end, we relied upon hypertension as an endophenotype of CHD and applied a
      multivariate sib-pair method in order to search for oligogenic marker
      configurations for which the sib-sib similarities deviated from the parent
      offspring similarities. Indeed, the latter similarities are always "0.5"
      irrespective of the affection status of parents and offspring. Loci with
      significant contributions to the oligogenic marker configuration constituted a
      CHD-specific genetic vector space. We found several ethnicity-independent
      signals. One signal on chromosome 8 may relate to the CYP11B1/CYP11B2 genes.

PMID- 14975128
TI  - Correlation between quantitative traits and correlation between corresponding LOD
      scores: detection of pleiotropic effects.
AB  - BACKGROUND: We address the question of whether statistical correlations among
      quantitative traits lead to correlation of linkage results of these traits. Five
      measured quantitative traits (total cholesterol, fasting glucose, HDL
      cholesterol, blood pressure, and triglycerides), and one derived quantitative
      trait (total cholesterol divided by the HDL cholesterol) are used for phenotype
      correlation studies. Four of them are used for linkage analysis. RESULTS: We show
      that although correlation among phenotypes partially reflects the correlation
      among linkage analysis results, the LOD-score correlations are on average low.
      The most significant peaks found by using different traits do not often overlap.
      CONCLUSION: Studying covariances at specific locations in LOD scores may provide
      clues for further bivariate linkage analyses.

PMID- 14975129
TI  - Genome-wide linkage scan on estimated breeding values for a quantitative trait.
AB  - BACKGROUND: A genome-wide linkage scan was performed on Replicate 1 of the
      simulated data for fasting triglyceride levels. The aim of this study was to
      implement mixed-model methodology to estimate breeding values for each individual
      for this trait and to assess the merit of these breeding values in linkage
      analysis. These breeding values utilize all the pedigree information, and the
      genetic and phenotypic correlations with other measured traits across the two
      cohorts. A genome-wide linkage scan was run on both the new breeding value traits
      and the original traits. RESULTS: Using breeding values, a maximum LOD of 7.78
      was found on chromosome 5 at a position very close to a gene underlying the
      triglyceride levels. This effect was not detected using the original trait.
      CONCLUSION: The results imply that estimating breeding values may be a suitable
      method of deriving traits for use in genome-wide scans.

PMID- 14975130
TI  - Bivariate linkage analysis of cholesterol and triglyceride levels in the
      Framingham Heart Study.
AB  - We performed a bivariate analysis on cholesterol and triglyceride levels on data
      from the Framingham Heart Study using a new score statistic developed for the
      detection of potential pleiotropic, or cluster, genes. Univariate score
      statistics were also computed for each trait. At a significance level 0.001,
      linkage signals were found at markers GATA48B01 on chromosome 1, GATA21C12 on
      chromosome 8, and ATA55A11 on chromosome 16 using the bivariate analysis. At the
      same significance level, linkage signals were found at markers 036yb8 on
      chromosome 3 and GATA3F02 on chromosome 12 using the univariate analysis. A
      strong linkage signal was also found at marker GATA112F07 by both the bivariate
      analysis and the univariate analysis, a marker for which evidence for linkage had
      been reported previously in a related study.

PMID- 14975131
TI  - Screening the genome to detect an association with hypertension.
AB  - We report tree-based association analysis as applied to the two Framingham
      cohorts and to the first replication of the simulated data obtained from the
      Genetic Analysis Workshop 13. For this analysis, familial association is ignored.
      The two endpoints examined are hypertension status at initial visit and time-to
      hypertension, using a censored data approach. Although linkage association has
      previously been reported with hypertension, we found no association using the
      tree-based methodology.

PMID- 14975132
TI  - Mapping complex traits using Random Forests.
AB  - Random Forest is a prediction technique based on growing trees on bootstrap
      samples of data, in conjunction with a random selection of explanatory variables
      to define the best split at each node. In the case of a quantitative outcome, the
      tree predictor takes on a numerical value. We applied Random Forest to the first
      replicate of the Genetic Analysis Workshop 13 simulated data set, with the
      sibling pairs as our units of analysis and identity by descent (IBD) at selected
      loci as our explanatory variables. With the knowledge of the true model, we
      performed two sets of analyses on three phenotypes: HDL, triglycerides, and
      glucose. The goal was to approach the mapping of complex traits from a
      multivariate perspective. The first set of analyses mimics a candidate gene
      approach with a high proportion of true genes among the predictors while the
      second set represents a genome scan analysis using microsatellite markers. Random
      Forest was able to identify a few of the major genes influencing the phenotypes,
      such as baseline HDL and triglycerides, but failed to identify the major genes
      regulating baseline glucose levels.

PMID- 14975133
TI  - A genome-wide scan using tree-based association analysis for candidate loci
      related to fasting plasma glucose levels.
AB  - BACKGROUND: In the analysis of complex traits such as fasting plasma glucose
      levels, researchers often adjust the trait for some important covariates before
      assessing gene susceptibility, and may at times encounter confounding among the
      covariates and the susceptible genes. Previously, the tree-based method has been
      employed to accommodate the heterogeneity in complex traits. In this study, we
      performed a genome-wide screen on fasting glucose levels in the offspring
      generation of the Framingham Heart Study provided by the Genetic Analysis
      Workshop 13. We defined one quantitative trait and converted it to a dichotomous
      trait based on a predetermined cut-off value, and performed association analyses
      using regression and classification trees for the two traits, respectively. A
      marker was interpreted as positive if at least one of its alleles exhibited
      association in both analyses. Our purpose was to identify candidate genes
      susceptible to fasting glucose levels in the presence of other covariates. The
      covariates entered in the analysis including sex, body mass index, and lipids
      (total plasma cholesterol, high density lipoprotein cholesterol, and
      triglycerides) of the subjects, and those of their parents. RESULTS: Four out of
      seven positive regions in chromosomes 1, 2, 6, 11, 16, 18, and 19 from our
      analyses harbored or were very close to previously reported diabetes related
      genes or potential candidate genes. CONCLUSION: This screen method that employed
      tree-based association showed promise for identifying candidate loci in the
      presence of covariates in genome scans for complex traits.

PMID- 14975134
TI  - Use of tree-based models to identify subgroups and increase power to detect
      linkage to cardiovascular disease traits.
AB  - BACKGROUND: Our goal was to identify subgroups of sib pairs from the Framingham
      Heart Study data set that provided higher evidence of linkage to particular
      candidate regions for cardiovascular disease traits. The focus of this method is
      not to claim identification of significant linkage to a particular locus but to
      show that tree models can be used to identify subgroups for use in selected sib
      pair sampling schemes. RESULTS: We report results using a novel recursive
      partitioning procedure to identify subgroups of sib pairs with increased evidence
      of linkage to systolic blood pressure and other cardiovascular disease-related
      quantitative traits, using the Framingham Heart Study data set provided by the
      Genetic Analysis Workshop 13. This procedure uses a splitting rule based on
      Haseman-Elston regression that recursively partitions sib-pair data into
      homogeneous subgroups. CONCLUSIONS: Using this procedure, we identified a
      subgroup definition for use as a selected sib-pair sampling scheme. Using the
      characteristics that define the subgroup with higher evidence for linkage, we
      have identified an area of focus for further study.

PMID- 14975135
TI  - Risk factors for coronary artery disease and the use of neural networks to
      predict the presence or absence of high blood pressure.
AB  - BACKGROUND: The Framingham Heart Study was initiated in 1948 as a long-term
      longitudinal study to identify risk factors associated with cardiovascular
      disease (CVD). Over the years the scope of the study has expanded to include
      offspring and other family members of the original cohort, marker data useful for
      gene mapping and information on other diseases. As a result, it is a rich
      resource for many areas of research going beyond the original goals. As part of
      the Genetic Analysis Workshop 13, we used data from the study to evaluate the
      ability of neural networks to use CVD risk factors as training data for
      predictions of normal and high blood pressure. RESULTS: Applying two different
      strategies to the coding of CVD risk data as risk factors (one longitudinal and
      one independent of time), we found that neural networks could not be trained to
      clearly separate individuals into normal and high blood pressure groups. When
      training was successful, validation was not, suggesting over-fitting of the
      model. When the number of parameters was reduced, training was not as good. An
      analysis of the input data showed that the neural networks were, in fact, finding
      consistent patterns, but that these patterns were not correlated with the
      presence or absence of high blood pressure. CONCLUSION: Neural network analysis,
      applied to risk factors for CVD in the Framingham data, did not lead to a clear
      classification of individuals into groups with normal and high blood pressure.
      Thus, although high blood pressure may itself be a risk factor for CVD, it does
      not appear to be clearly predictable using observations from a set of other CVD
      risk factors.

PMID- 14975136
TI  - Multivariate sib-pair linkage analysis of longitudinal phenotypes by three step
      wise analysis approaches.
AB  - BACKGROUND: Current statistical methods for sib-pair linkage analysis of complex
      diseases include linear models, generalized linear models, and novel data mining
      techniques. The purpose of this study was to further investigate the utility and
      properties of a novel pattern recognition technique (step-wise discriminant
      analysis) using the chromosome 10 linkage data from the Framingham Heart Study
      and by comparing it with step-wise logistic regression and linear regression.
      RESULTS: The three step-wise approaches were compared in terms of statistical
      significance and gene localization. Step-wise discriminant linkage analysis
      approach performed best; next was step-wise logistic regression; and step-wise
      linear regression was the least efficient because it ignored the categorical
      nature of disease phenotypes. Nevertheless, all three methods successfully
      identified the previously reported chromosomal region linked to human
      hypertension, marker GATA64A09. We also explored the possibility of using the
      discriminant analysis to detect gene x gene and gene x environment interactions.
      There was evidence to suggest the existence of gene x environment interactions
      between markers GATA64A09 or GATA115E01 and hypertension treatment and gene x
      gene interactions between markers GATA64A09 and GATA115E01. Finally, we answered
      the theoretical question "Is a trichotomous phenotype more efficient than a
      binary?" Unlike logistic regression, discriminant sib-pair linkage analysis might
      have more power to detect linkage to a binary phenotype than a trichotomous one.
      CONCLUSION: We confirmed our previous speculation that step-wise discriminant
      analysis is useful for genetic mapping of complex diseases. This analysis also
      supported the possibility of the pattern recognition technique for investigating
      gene x gene or gene x environment interactions.

PMID- 14975137
TI  - Locating disease genes using Bayesian variable selection with the Haseman-Elston
      method.
AB  - BACKGROUND: We applied stochastic search variable selection (SSVS), a Bayesian
      model selection method, to the simulated data of Genetic Analysis Workshop 13. We
      used SSVS with the revisited Haseman-Elston method to find the markers linked to
      the loci determining change in cholesterol over time. To study gene-gene
      interaction (epistasis) and gene-environment interaction, we adopted prior
      structures, which incorporate the relationship among the predictors. This allows
      SSVS to search in the model space more efficiently and avoid the less likely
      models. RESULTS: In applying SSVS, instead of looking at the posterior
      distribution of each of the candidate models, which is sensitive to the setting
      of the prior, we ranked the candidate variables (markers) according to their
      marginal posterior probability, which was shown to be more robust to the prior.
      Compared with traditional methods that consider one marker at a time, our method
      considers all markers simultaneously and obtains more favorable results.
      CONCLUSIONS: We showed that SSVS is a powerful method for identifying linked
      markers using the Haseman-Elston method, even for weak effects. SSVS is very
      effective because it does a smart search over the entire model space.

PMID- 14975138
TI  - Linkage analysis of the simulated data - evaluations and comparisons of methods.
AB  - The goal of this study is to evaluate, compare, and contrast several standard and
      new linkage analysis methods. First, we compare a recently proposed confidence
      set approach with MAPMAKER/SIBS. Then, we evaluate a new Bayesian approach that
      accounts for heterogeneity. Finally, the newly developed software SIMPLE is
      compared with GENEHUNTER. We apply these methods to several replicates of the
      Genetic Analysis Workshop 13 simulated data to assess their ability to detect the
      high blood pressure genes on chromosome 21, whose positions were known to us
      prior to the analyses. In contrast to the standard methods, most of the new
      approaches are able to identify at least one of the disease genes in all the
      replicates considered.

PMID- 14975139
TI  - Approaches to mapping genetically correlated complex traits.
AB  - Our Markov chain Monte Carlo (MCMC) methods were used in linkage analyses of the
      Framingham Heart Study data using all available pedigrees. Our goal was to detect
      and map loci associated with covariate-adjusted traits log triglyceride (lnTG)
      and high-density lipoprotein cholesterol (HDL) using multipoint LOD score
      analysis, Bayesian oligogenic linkage analysis and identity-by-descent (IBD)
      scoring methods. Each method used all marker data for all markers on a
      chromosome. Bayesian linkage analysis detected a linkage signal on chromosome 7
      for lnTG and HDL, corroborating previously published results. However, these
      results were not replicated in a classical linkage analysis of the data or by
      using IBD scoring methods.We conclude that Bayesian linkage analysis provides a
      powerful paradigm for mapping trait loci but interpretation of the Bayesian
      linkage signals is subjective. In the absence of a LOD score method accommodating
      genetically complex traits and linkage heterogeneity, validation of these signals
      remains elusive.

PMID- 14975140
TI  - On different approximations to multilocus identity-by-descent calculations and
      the resulting power of variance component-based linkage analysis.
AB  - An empirical comparison between three different methods for estimation of pair
      wise identity-by-descent (IBD) sharing at marker loci was conducted in order to
      quantify the resulting differences in power and localization precision in
      variance components-based linkage analysis. On the examined simulated, error-free
      data set, it was found that an increase in accuracy of allele sharing calculation
      resulted in an increase in power to detect linkage. Linkage analysis based on
      approximate multi-marker IBD matrices computed by a Markov chain Monte Carlo
      approach was much more powerful than linkage analysis based on exact single
      marker IBD probabilities. A "multiple two-point" approximation to true
      "multipoint" IBD computation was found to be roughly intermediate in power. Both
      multi-marker approaches were similar to each other in accuracy of localization of
      the quantitative trait locus and far superior to the single-marker approach. The
      overall conclusions of this study with respect to power are expected to also hold
      for different data structures and situations, even though the degree of
      superiority of one approach over another depends on the specific circumstances.
      It should be kept in mind, however, that an increase in computational accuracy is
      expected to go hand in hand with a decrease in robustness to various sources of
      errors.

PMID- 14975141
TI  - Importance sampling method of correction for multiple testing in affected sib
      pair linkage analysis.
AB  - Using the Genetic Analysis Workshop 13 simulated data set, we compared the
      technique of importance sampling to several other methods designed to adjust p
      values for multiple testing: the Bonferroni correction, the method proposed by
      Feingold et al., and naive Monte Carlo simulation. We performed affected sib-pair
      linkage analysis for each of the 100 replicates for each of five binary traits
      and adjusted the derived p-values using each of the correction methods. The type
      I error rates for each correction method and the ability of each of the methods
      to detect loci known to influence trait values were compared. All of the methods
      considered were conservative with respect to type I error, especially the
      Bonferroni method. The ability of these methods to detect trait loci was also
      low. However, this may be partially due to a limitation inherent in our binary
      trait definitions.

PMID- 14975142
TI  - Mapping loci influencing blood pressure in the Framingham pedigrees using model
      free LOD score analysis of a quantitative trait.
AB  - This paper presents a method of performing model-free LOD-score based linkage
      analysis on quantitative traits. It is implemented in the QMFLINK program. The
      method is used to perform a genome screen on the Framingham Heart Study data. A
      number of markers that show some support for linkage in our study coincide
      substantially with those implicated in other linkage studies of hypertension.
      Although the new method needs further testing on additional real and simulated
      data sets we can already say that it is straightforward to apply and may offer a
      useful complementary approach to previously available methods for the linkage
      analysis of quantitative traits.

PMID- 14975143
TI  - A model-integrated multipoint Bayesian analysis of hypertension in the Framingham
      Heart Study data finds little evidence of linkage.
AB  - This Genetic Analysis Workshop 13 contribution presents a linkage analysis of
      hypertension in the Framingham data based on the posterior probability of
      linkage, or PPL. We dichotomized the phenotype, coding individuals who had been
      treated for hypertension at any time, as well as those with repeated high blood
      pressure measurements, as affected. Here we use a new variation on the multipoint
      PPL that incorporates integration over the genetic model. PPLs were computed for
      chromosomes 1 through 5, 11, 14, and 17 and remained below the 2% assumed prior
      probability of linkage for 73% of the locations examined. The maximum PPL of 4.5%
      was obtained on chromosome 1 at 178 cM. Although this is more than twice the
      assumed prior probability of linkage, it is well below a level at which we would
      recommend committing substantial additional resources to molecular follow-up.
      While the PPL analysis of this data remains inconclusive, Bayesian methodology
      gives us a clear mechanism for using the information gained here in further
      studies.

PMID- 14975144
TI  - Linkage analysis of adult height with parent-of-origin effects in the Framingham
      Heart Study.
AB  - Current linkage analysis methods for quantitative traits do not usually
      incorporate imprinting effects. Here, we carried out genome-wide linkage analysis
      for loci influencing adult height in the Framingham Heart Study subjects using
      variance components while allowing for imprinting effects. We used a sex-averaged
      map for the 22 autosomes, while chromosomes 6, 14, 18, and 19 were also analyzed
      using sex-specific maps. We compared results from these four analyses: 1) non
      imprinted with sex-averaged maps, 2) imprinted with sex-averaged maps, 3) non
      imprinted with sex-specific maps, and 4) imprinted with sex-specific maps. We
      found four regions on three chromosomes (14q32, 18p11-q21, 18q21-22, and 19q13)
      with LOD scores above 2.0, with a maximum LOD score of 3.12, allowing for
      imprinting and sex-specific maps, at D18S1364 on 18q21. While we obtained
      significant evidence of imprinting effects in both the 18p11-q21 and 19q13
      regions when using sex-averaged maps, there were no significant differences
      between the imprinted and non-imprinted LOD scores when we used sex-specific
      maps. Our results illustrate the importance of allowing for gender-specific
      effects in linkage analyses, whether these are in the form of gender-specific
      recombination frequencies, or in the form of imprinting effects.

PMID- 14975145
TI  - Linkage analysis of systolic blood pressure: a score statistic and computer
      implementation.
AB  - A genome-wide linkage analysis was conducted on systolic blood pressure using a
      score statistic. The randomly selected Replicate 34 of the simulated data was
      used. The score statistic was applied to the sibships derived from the general
      pedigrees. An add-on R program to GENEHUNTER was developed for this analysis and
      is freely available.

PMID- 14975146
TI  - Genome-wide linkage analysis of blood pressure under locus heterogeneity.
AB  - We describe a method for mapping quantitative trait loci that allows for locus
      heterogeneity. A genome-wide linkage analysis of blood pressure was performed
      using sib-pair data from the Framingham Heart Study. Evidence of linkage was
      found on four markers (GATA89G08, GATA23D06, GATA14E09, and 049xd2) at a
      significance level of 0.01. Two of them (GATA14E09 and 049xd2) seem to overlap
      with linkage signals reported previously, while the other two are not linked to
      any known signals.

PMID- 14975147
TI  - Segregation analysis comparing liability and quantitative trait models for
      hypertension using the Genetic Analysis Workshop 13 simulated data.
AB  - Discrete (qualitative) data segregation analysis may be performed assuming the
      liability model, which involves an underlying normally distributed quantitative
      phenotype. The appropriateness of the liability model for complex traits is
      unclear. The Genetic Analysis Workshop 13 simulated data provides measures on
      systolic blood pressure, a highly complex trait, which may be dichotomized into a
      discrete trait (hypertension). We perform segregation analysis under the
      liability model of hypertensive status as a qualitative trait and compare this
      with results using systolic blood pressure as a quantitative trait (without prior
      knowledge at that stage of the true underlying simulation model) using 1050
      pedigrees ascertained from four replicates on the basis of at least one affected
      member. Both analyses identify models with major genes and polygenic components
      to explain the family aggregation of systolic blood pressure. Neither of the
      methods estimates the true parameters well (as the true model is considerably
      more complicated than those considered for the analysis), but both identified the
      most complicated model evaluated as the preferred model. Segregation analysis of
      complex diseases using relatively simple models is unlikely to provide accurate
      parameter estimates but is able to indicate major gene and/or polygenic
      components in familial aggregation of complex diseases.

PMID- 14975148
TI  - Age-of-onset of hypertension vs. a single measurement of systolic blood pressure
      in a combined linkage and segregation analysis.
AB  - BACKGROUND: Often, multiple measures of a trait are available in a genetic
      linkage analysis. We compare Monte Carlo Markov chain analysis of two very
      different measures of hypertension in the simulated Genetic Analysis Workshop 13
      data to examine how choice of measure affects the results. The measures selected
      were age-of-onset of hypertension and systolic blood pressure at first visit.
      RESULTS: In combined segregation and linkage analysis of the complete pedigrees
      using the first replicate of the simulated data with missing values, we found
      that the age-of-onset analysis was better at identifying "slope" genes, while the
      systolic blood pressure analysis was better at identifying "baseline" genes.
      CONCLUSION: Analysis of different trait measures may identify different trait
      related genes. When linkage analysis is conducted on multiple trait measures, a
      linkage signal found for only one measure can represent a true trait locus.

PMID- 14975149
TI  - Bivariate variance-component analysis, with application to systolic blood
      pressure and total cholesterol levels in the Framingham Heart Study.
AB  - BACKGROUND: The correlations between systolic blood pressure (SBP) and total
      cholesterol levels (CHOL) might result from genetic or environmental factors that
      determine variation in the phenotypes and are shared by family members. Based on
      330 nuclear families in the Framingham Heart Study, we used a multivariate normal
      model, implemented in the software FISHER, to estimate genetic and shared
      environmental components of variation and genetic and shared environmental
      correlation between the phenotypes. The natural logarithm of the phenotypes
      measured at the last visit in both Cohort 1 and 2 was used in the analyses. The
      antihypertensive treatment effect was corrected before adjustment of the systolic
      blood pressure for age, sex, and cohort. RESULTS: The univariate correlation
      coefficient was statistically significant for sibling pairs and parent-offspring
      pairs, but not significant for spouse pairs. In the bivariate analysis, the cross
      trait correlation coefficients were not statistically significant for all
      relative pairs. The shared environmental correlation was statistically
      significant, but the genetic correlation was not significant. CONCLUSION: There
      is no significant evidence for a close genetic correlation between systolic blood
      pressure and total cholesterol levels. However, some shared environmental factors
      may determine the variation of both phenotypes.

PMID- 14975150
TI  - Genome-wide linkage scan for genes affecting longitudinal trends in systolic
      blood pressure.
AB  - Only one genome scan to date has attempted to make use of the longitudinal data
      available in the Framingham Heart Study, and this attempt yielded evidence of
      linkage to a gene for mean systolic blood pressure. We show how the additional
      information available in these longitudinal data can be utilized to examine
      linkages for not only mean systolic blood pressure (SBP), but also for its trend
      with age and its variability. Prior to linkage analysis, individuals treated for
      hypertension were adjusted to account for right-censoring of SBP. Regressions on
      age were fitted to obtain orthogonal measures of slope, curvature, and residual
      variance of SBP that were then used as dependent variables in the model-free
      linkage program SIBPAL. We included mean age, gender, and cohort as covariates in
      the analysis. To improve power, sibling pairs were weighted for informativity
      using weights derived from both the marker and trait. The most significant
      results from our analyses were found on chromosomes 12, 15, and 17 for mean SBP,
      and chromosome 20 for both SBP slope and curvature.

PMID- 14975151
TI  - Genome scan linkage results for longitudinal systolic blood pressure phenotypes
      in subjects from the Framingham Heart Study.
AB  - The relationship between elevated blood pressure and cardiovascular and
      cerebrovascular disease risk is well accepted. Both systolic and diastolic
      hypertension are associated with this risk increase, but systolic blood pressure
      appears to be a more important determinant of cardiovascular risk than diastolic
      blood pressure. Subjects for this study are derived from the Framingham Heart
      Study data set. Each subject had five records of clinical data of which systolic
      blood pressure, age, height, gender, weight, and hypertension treatment were
      selected to characterize the phenotype in this analysis. We modeled systolic
      blood pressure as a function of age using a mixed modeling methodology that
      enabled us to characterize the phenotype for each individual as the individual's
      deviation from the population average rate of change in systolic blood pressure
      for each year of age while controlling for gender, body mass index, and
      hypertension treatment. Significant (p = 0.00002) evidence for linkage was found
      between this normalized phenotype and a region on chromosome 1. Similar linkage
      results were obtained when we estimated the phenotype while excluding values
      obtained during hypertension treatment. The use of linear mixed models to define
      phenotypes is a methodology that allows for the adjustment of the main factor by
      covariates. Future work should be done in the area of combining this phenotype
      estimation directly with the linkage analysis so that the error in estimating the
      phenotype can be properly incorporated into the genetic analysis, which, at
      present, assumes that the phenotype is measured (or estimated) without error.

PMID- 14975152
TI  - Using an age-at-onset phenotype with interval censoring to compare methods of
      segregation and linkage analysis in a candidate region for elevated systolic
      blood pressure.
AB  - BACKGROUND: Genetic studies of complex disorders such as hypertension often
      utilize families selected for this outcome, usually with information obtained at
      a single time point. Since age-at-onset for diagnosed hypertension can vary
      substantially between individuals, a phenotype based on long-term follow up in
      unselected families can yield valuable insights into this disorder for the
      general population. METHODS: Genetic analyses were conducted using 2884
      individuals from the largest 330 families of the Framingham Heart Study. A
      longitudinal phenotype was constructed using the age at an examination when
      systolic blood pressure (SBP) first exceeds 139 mm Hg. An interval for age-at
      onset was created, since the exact time of onset was unknown. Time-fixed (sex,
      study cohort) and time-varying (body mass index, daily cigarette and alcohol
      consumption) explanatory variables were included. RESULTS: Segregation analysis
      for a major gene effect demonstrated that the major gene effect parameter was
      sensitive to the choice for age-at-onset. Linkage analyses for age-at-onset were
      conducted using 1537 individuals in 52 families. Evidence for putative genes
      identified on chromosome 17 in a previous linkage study using a quantitative SBP
      phenotype for these data was not confirmed. CONCLUSIONS: Interval censoring for
      age-at-onset should not be ignored. Further research is needed to explain the
      inconsistent segregation results between the different age-at-onset models
      (regressive threshold and proportional hazards) as well as the inconsistent
      linkage results between the longitudinal phenotypes (age-at-onset and
      quantitative).

PMID- 14975153
TI  - Nonparametric longitudinal allele-sharing model.
AB  - Basically no methods are available for the analysis of quantitative traits in
      longitudinal genetic epidemiological studies. We introduce a nonparametric
      factorial design for longitudinal data on independent sib pairs, modelling the
      phenotypic quadratic differences as the dependent variable. Factors are the
      number of alleles shared identically by descent (IBD) and the age categories at
      which the dependent variable is measured, allowing for dependence due to age. To
      identify a linked marker a rank statistic tests the influence of IBD group on
      phenotypic quadratic differences. No assumptions are made on normality or
      variances of the dependent variable. We apply our method to 71 sib pairs from the
      Framingham Heart Study data provided at the Genetic Analysis Workshop 13. For all
      15 available markers on chromosome 17 we analyzed the influence on systolic blood
      pressure. In addition, different selection strategies to sample from the whole
      data are discussed.

PMID- 14975154
TI  - Genome-wide linkage analysis of systolic blood pressure slope using the Genetic
      Analysis Workshop 13 data sets.
AB  - Systolic blood pressure (SBP) is an age-dependent complex trait for which both
      environmental and genetic factors may play a role in explaining variability among
      individuals. We performed a genome-wide scan of the rate of change in SBP over
      time on the Framingham Heart Study data and one randomly selected replicate of
      the simulated data from the Genetic Analysis Workshop 13. We used a variance
      component model to carry out linkage analysis and a Markov chain Monte Carlo
      based multiple imputation approach to recover missing information. Furthermore,
      we adopted two selection strategies along with the multiple imputation to deal
      with subjects taking antihypertensive treatment. The simulated data were used to
      compare these two strategies, to explore the effectiveness of the multiple
      imputation in recovering varying degrees of missing information, and its impact
      on linkage analysis results. For the Framingham data, the marker with the highest
      LOD score for SBP slope was found on chromosome 7. Interestingly, we found that
      SBP slopes were not heritable in males but were for females; the marker with the
      highest LOD score was found on chromosome 18. Using the simulated data, we found
      that handling treated subjects using the multiple imputation improved the linkage
      results. We conclude that multiple imputation is a promising approach in
      recovering missing information in longitudinal genetic studies and hence in
      improving subsequent linkage analyses.

PMID- 14975155
TI  - Longitudinal familial analysis of blood pressure involving parametric
      (co)variance functions.
AB  - BACKGROUND: For analyzing longitudinal familial data we adopted a log-linear form
      to incorporate heterogeneity in genetic variance components over the time, and
      additionally a serial correlation term in the genetic effects at different levels
      of ages. Due to the availability of multiple measures on the same individual, we
      permitted environmental correlations that may change across time. RESULTS:
      Systolic blood pressure from family members from the first and second cohort was
      used in the current analysis. Measures of subjects receiving hypertension
      treatment were set as censored values and they were corrected. An initial check
      of the variance and covariance functions proposed for analyzing longitudinal
      familial data, using empirical semi-variogram plots, indicated that the observed
      trait dispersion pattern follows the assumptions adopted. CONCLUSION: The
      corrections for censored phenotypes based on ordinary linear models may be an
      appropriate simple model to correct the data, ensuring that the original
      variability in the data was retained. In addition, empirical semi-variogram plots
      are useful for diagnosis of the (co)variance model adopted.

PMID- 14975156
TI  - Genome-wide linkage analysis of the tracking of systolic blood pressure using a
      mixed model.
AB  - BACKGROUND: Elevated blood pressure in middle age is a major risk factor for
      subsequent cardiovascular complications. An important longitudinal characteristic
      of blood pressure is the "tracking phenomenon". Tracking is defined as the
      persistence of the rank of a person's blood pressure level in a group over a long
      period of time. In this analysis, we used the Framingham data to investigate
      whether there are some genes responsible for this phenomenon. RESULTS: Both two
      point and multipoint linkage analyses were applied to family members with
      complete data only and to all family data with missing values imputed by a
      Gaussian model. The results of two-point linkage analysis indicated that two loci
      for linkage with the intercept were on chromosomes 10 and 13, and two loci for
      linkage with both slope and intercept were on chromosomes 1 and 3. Multipoint
      linkage analysis indicated only one region, 200-240 cM on chromosome 1, to be
      linked with both intercept and slope. For the intercept of SBP, the highest LOD
      (4.43) was found at 214 cM when missing data were imputed, and the highest LOD
      (2.81) was at 231 cM for the complete case data. For the slope of SBP, the
      highest multipoint LODs were 3.63 at 227 cM and 2.02 at 234 cM for the complete
      case data and imputation data, respectively. CONCLUSION: One or more genes in the
      range of 200-240 cM on chromosome 1 may be related to the tracking phenomenon of
      SBP.

PMID- 14975157
TI  - A cautionary note on the appropriateness of using a linkage resource for an
      association study.
AB  - BACKGROUND: Utilizing a linkage resource for association analysis requires
      consideration both of the marker data used and correlations among relatives in
      pedigrees. We previously developed a method for association testing in pedigrees.
      We applied our method to 50 replicates of microsatellite data surrounding five
      genes involved in high-density lipoprotein (HDL) in the Genetic Analysis Workshop
      13 (GAW13) simulated data and examined association with HDL as well as linkage
      disequilibrium (LD) between markers. RESULTS: Although no association was
      intentionally simulated, we found significant evidence of weak LD between
      microsatellite markers (flanking/~5 cM from the genes), in some but not all
      replicates. This level of LD compared well to that observed in the real GAW13
      Framingham data. Only one region had sufficient replicates to assess power, and
      this was low (12.5-20.8%). More power was attained using all individuals and
      accounting for relationships, compared with one independent individual/pedigree,
      although this was not significant due to small sample sizes. Not accounting for
      relatedness inflated statistical significance (p < 0.0001). CONCLUSION: A
      correction for dependence is necessary in association studies to avoid an
      inflation of significance probabilities. Our results further illustrate that use
      of microsatellite marker data is not an effective approach for association
      testing.

PMID- 14975158
TI  - Comparison between two analytic strategies to detect linkage to obesity with
      genetically determined age of onset: the Framingham Heart Study.
AB  - BACKGROUND: Genes have been found to influence the age of onset of several
      diseases and traits. The occurrence of many chronic diseases, obesity included,
      appears to be strongly age-dependent. However, an analysis of potential age of
      onset genes for obesity has yet to be reported. There are at least two analytic
      methods for determining an age of onset gene. The first is to consider a person
      affected if they possess the trait before a certain age (an early age of onset
      phenotype). The second is to define the phenotype based on the residual from a
      survival analysis. RESULTS: No regions provided evidence for linkage at the more
      stringent level of p < 0.001. However, five regions showed consistent suggestive
      evidence for linkage (one marker with p < 0.01 and a second contiguous marker at
      p < 0.05). These regions were chromosome 1 (280-294 cM) and chromosome 16 (56-64
      cM) for overweight using the survival analysis residual method and chromosome 13
      (102-122 cM), chromosome 17 (127-138 cM), and chromosome 19 (23-47 cM) for obese
      before age 35. CONCLUSION: Only one region (chromosome 19 at 23-47 cM) showed
      somewhat consistent results between the two analytic methods. Potential reasons
      for inconsistent results between the two methods, as well as their strengths and
      weaknesses, are discussed. The use of both methods together to explore the
      genetics of the age of onset of a trait may prove to be beneficial in determining
      a gene that is linked only to an early age of onset phenotype versus one that
      determines age of onset through all age groups.

PMID- 14975159
TI  - Genome scan for body mass index and height in the Framingham Heart Study.
AB  - BACKGROUND: Body mass index (BMI) and adult height are moderately and highly
      heritable traits, respectively. To investigate the genetic background of these
      quantitative phenotypes, we performed a linkage genome scan in the extended
      pedigrees of the Framingham Heart Study. Two variance-components approaches
      (SOLAR and MERLIN-VC) and one regression method (MERLIN-REGRESS) were applied to
      the data. RESULTS: Evidence for linkage to BMI was found on chromosomes 16 and 6
      with maximum LOD scores of 3.2 and 2.7, respectively. For height, all markers
      showing a LOD score greater than 1 in our analysis correspond to previously
      reported linkage regions, including chromosome 6q with a maximum LOD score of
      2.45 and chromosomes 9, 12, 14, 18, and 22. Regarding the analysis, the three
      applied methods gave very similar results in this unselected sample with
      approximately normally distributed traits. CONCLUSION: Our analysis resulted in
      the successful identification of linked regions. In particular, we consider the
      regions on chromosomes 6 and 16 for BMI and the regions on chromosomes 6, 9, and
      12 for stature interesting for fine mapping and candidate gene studies.

PMID- 14975160
TI  - Linkage mapping of total cholesterol level in a young cohort via nonparametric
      regression.
AB  - BACKGROUND: Compared to model-based approaches, nonparametric methods for
      quantitative trait loci mapping are more robust to deviations in distributional
      assumptions. In this study, we modify a nonparametric regression method and the
      "contrast function"- based regression method to analyze total cholesterol level
      in the younger cohort (the offspring generation) of the Genetic Analysis Workshop
      13 simulated data set. RESULTS: We obtained significant evidence of linkage near
      four of the six non-sex-specific genes in at least 30% of the replicates.
      CONCLUSIONS: The proposed nonparametric method seems to be a powerful robust
      alternative to distribution-based methods.

PMID- 14975161
TI  - Comparison of linkage analysis methods for genome-wide scanning of extended
      pedigrees, with application to the TG/HDL-C ratio in the Framingham Heart Study.
AB  - BACKGROUND: High triglycerides (TG) and low high-density lipoprotein cholesterol
      (HDL-C) jointly increase coronary disease risk. We performed linkage analysis for
      TG/HDL-C ratio in the Framingham Heart Study data as a quantitative trait, using
      methods implemented in LINKAGE, GENEHUNTER (GH), MCLINK, and SOLAR. Results were
      compared to each other and to those from a previous evaluation using SOLAR for
      TG/HDL-C ratio on this sample. We also investigated linked pedigrees in each
      region using by-pedigree analysis. RESULTS: Fourteen regions with at least
      suggestive linkage evidence were identified, including some that may increase and
      some that may decrease coronary risk. Ten of the 14 regions were identified by
      more than one analysis, and several of these regions were not previously
      detected. The best regions identified for each method were on chromosomes 2 (LOD
      = 2.29, MCLINK), 5 (LOD = 2.65, GH), 7 (LOD = 2.67, SOLAR), and 22 (LOD = 3.37,
      LINKAGE). By-pedigree multi-point LOD values in MCLINK showed linked pedigrees
      for all five regions, ranging from 3 linked pedigrees (chromosome 5) to 14 linked
      pedigrees (chromosome 7), and suggested localizations of between 9 cM and 27 cM
      in size. CONCLUSION: Reasonable concordance was found across analysis methods. No
      single method identified all regions, either by full sample LOD or with by
      pedigree analysis. Concordance across methods appeared better at the pedigree
      level, with many regions showing by-pedigree support in MCLINK when no evidence
      was observed in the full sample. Thus, investigating by-pedigree linkage evidence
      may provide a useful tool for evaluating linkage regions.

PMID- 14975162
TI  - Familial aggregation of components of the multiple metabolic syndrome in the
      Framingham Heart and Offspring Cohorts: Genetic Analysis Workshop Problem 1.
AB  - BACKGROUND: The multiple metabolic syndrome is defined by a clustering of risk
      factors for cardiovascular disease. We sought to evaluate the familial
      correlations of the components of the syndrome using data from the Framingham
      Heart Study original and offspring cohorts as provided for the Genetic Analysis
      Workshop 13. Measures of plasma cholesterol (total and HDL), body mass index
      (BMI), and systolic blood pressure were used from selected calendar years of
      exams. Familial correlations were calculated using FCOR in S.A.G.E. RESULTS: The
      sibling correlations were relatively high for all measures and exams, from 0.17
      for systolic blood pressure to 0.27 for HDL cholesterol. The parent-child
      correlations were very similar, except for systolic blood pressure. The avuncular
      correlations were much smaller and the cousin correlations were even smaller. For
      HDL cholesterol the avuncular correlation was half the sibling correlation and
      the cousin correlation was half that again. Spousal correlations ranged from 0.07
      for systolic blood pressure to 0.34 for BMI. Correlations were somewhat lower
      from 1984 to 1987 examinations than from 1971 to 1975 examinations, except for
      spousal correlations for systolic blood pressure and BMI. CONCLUSION: The results
      of the family pair correlations are suggestive of genetic determinants of lipid
      levels and BMI. These components have been shown to be predictive of
      cardiovascular disease as well as diabetes. Genes in common with each of the
      components might also influence development of cardiovascular disease and
      diabetes, both complex diseases.

PMID- 14975163
TI  - Phenotypic, genetic, and genome-wide structure in the metabolic syndrome.
AB  - BACKGROUND: Insulin resistance, obesity, dyslipidemia, and high blood pressure
      characterize the metabolic syndrome. In an effort to explore the utility of
      different multivariate methods of data reduction to better understand the genetic
      influences on the aggregation of metabolic syndrome phenotypes, we calculated
      phenotypic, genetic, and genome-wide LOD score correlation matrices using five
      traits (total cholesterol, high density lipoprotein cholesterol, triglycerides,
      systolic blood pressure, and body mass index) from the Framingham Heart Study
      data set prepared for the Genetic Analysis Workshop 13, clinic visits 10 and 1
      for the original and offspring cohorts, respectively. We next applied factor
      analysis to summarize the relationship between these phenotypes. RESULTS: Factors
      generated from the genetic correlation matrix explained the most variation.
      Factors extracted using the other matrices followed a different pattern and
      suggest distinct effects. CONCLUSIONS: Given these results, different methods of
      multivariate data reduction may provide unique clues on the clustering of this
      complex syndrome.

PMID- 14975164
TI  - A QTL genome scan of the metabolic syndrome and its component traits.
AB  - BACKGROUND: Because high blood pressure, altered lipid levels, obesity, and
      diabetes so frequently occur together, they are sometimes collectively referred
      to as the metabolic syndrome. While there have been many studies of each
      metabolic syndrome trait separately, few studies have attempted to analyze them
      combined, i.e., as one composite variable, in quantitative trait linkage or
      association analysis. We used genotype and phenotype data from the Framingham
      Heart Study to perform a full-genome scan for quantitative trait loci underlying
      the metabolic syndrome. RESULTS: Heritability estimates for all of the covariate
      adjusted and age- and gender-standardized individual traits, and the composite
      metabolic syndrome trait, were all fairly high (0.39-0.62), and the composite
      trait was among the highest at 0.61. The composite trait yielded no regions with
      suggestive linkage by Lander and Kruglyak's criteria, although there were several
      noteworthy regions for individual traits, some of which were also observed for
      the composite variable. CONCLUSION: Despite its high heritability, the composite
      metabolic syndrome trait variable did not increase the power to detect or
      localize linkage peaks in this sample. However, this strategy and related methods
      of combining correlated individual traits deserve further investigation,
      particularly in settings with complex causal pathways.

PMID- 14975165
TI  - A genome-wide linkage scan for body mass index on Framingham Heart Study
      families.
AB  - BACKGROUND: Genome-wide scan data from a community-based sample was used to
      identify the genetic factors that affect body mass index (BMI). BMI was defined
      as weight (kg) over the square of height (m), where weight and height were
      obtained from the first measurement available between the ages of 40 and 50
      years. RESULTS: Significant familial correlations were observed in mother:father
      (spouse) relative pairs and in all relative pairs examined except parent:daughter
      pairs. Single-point sib-pair regression analysis provided nominal evidence for
      linkage (p < 0.05) of loci to BMI at 23 markers. Multi-point sib-pair regression
      analysis provided nominal evidence for linkage to BMI at 42 loci on 12
      chromosomes. Empirical p-values showed results consistent with the multi-point
      results; all but three of the loci identified by multi-point analysis were also
      significant. CONCLUSION: The largest regions of nominally significant linkage
      were found on chromosomes 2, 3, and 11. The most significant evidence for linkage
      was obtained with markers D2S1788, D2S1356, D2S1352, D3S1744, and D11S912 from
      multi-point sib-pair single-trait regression analysis. Our results are in
      agreement with some of the recently published reports on BMI using various data
      sets including the Framingham Heart Study data.

PMID- 14975166
TI  - HDL cholesterol in females in the Framingham Heart Study is linked to a region of
      chromosome 2q.
AB  - BACKGROUND: Despite strong evidence for a genetic component to variation in high
      density lipoprotein cholesterol levels (HDL-C), specific polymorphisms associated
      with normal variation in HDL-C have not been identified. It is known, however,
      that HDL-C levels are influenced in complex ways by factors related to age and
      sex. In this paper, we examined the evidence for age- and sex-specific linkage of
      HDL-C in a longitudinal sample of participants from the Framingham Heart Study.
      To determine if aging could influence our ability to detect linkage, we explored
      the evidence for linkage of HDL-C at three time points, t1, t2, and t3, spaced
      approximately 8 years apart and corresponding respectively to visits 11, 15, and
      20 for the original cohort and 1, 2, and 4 for the offspring and spouses.
      Additionally, to examine the effects of sex on linkage at each time point, we
      estimated the heritability and genetic correlation of HDL-C, performed linkage
      analysis of HDL-C, tested for genotype-by-sex interaction at a QTL, and performed
      linkage analysis of HDL-C in males and females separately. RESULTS AND
      CONCLUSION: In women, we found evidence for a QTL on chromosome 2q influencing
      HDL-C variation. Although the QTL could be detected in the combined sample of
      males and females at the first time point, the linkage was not significant at
      subsequent time points.

PMID- 14975167
TI  - Structural equation model-based genome scan for the metabolic syndrome.
AB  - BACKGROUND: The metabolic syndrome is characterized by the clustering of several
      traits, including obesity, hypertension, decreased levels of HDL cholesterol, and
      increased levels of glucose and triglycerides. Because these traits cluster,
      there are likely common genetic factors involved. RESULTS: We used a multivariate
      structural equation model (SEM) approach to scan the genome for loci involved in
      the metabolic syndrome. We found moderate evidence for linkage on chromosomes 2,
      3, 11, 13, and 15, and these loci appear to have different relative effects on
      the component traits of the metabolic syndrome. CONCLUSION: Our results suggest
      that the metabolic syndrome components, diabetes, obesity, and hypertension, are
      under the pleiotropic control of several loci.

PMID- 14975168
TI  - Search for genetic factors predisposing to atherogenic dyslipidemia.
AB  - BACKGROUND: Atherogenic dyslipidemia (AD) is a common feature in persons with
      premature coronary heart disease. While several linkage studies have been carried
      out to dissect the genetic etiology of lipid levels, few have investigated the AD
      lipid triad comprising elevated serum triglyceride, small low density lipoprotein
      (LDL) particles, and reduced high density lipoprotein (HDL) cholesterol levels.
      Here we report the results of a whole-genome screen for AD using the Framingham
      Heart Study population. RESULTS: Our analyses provide some evidence for linkage
      to AD on chromosomes 1q31, 3q29, 10q26, 14p12, 14q13, 16q24, 18p11, and 19q13.
      CONCLUSION: AD susceptibility is modulated by multiple genes in different
      chromosomes. Our study confirms results from other populations and suggests new
      areas of potential importance.

PMID- 14975169
TI  - Genomic regions linked to alcohol consumption in the Framingham Heart Study.
AB  - BACKGROUND: Pedigree, demographic, square-root transformed maximum alcohol
      (SRMAXAPD) and maximum cigarette (MAXCPD) consumption, and genome-wide scan data
      from the Framingham Heart Study (FHS) were used to investigate genetic factors
      that may affect alcohol and cigarette consumption in this population-based
      sample. RESULTS: A significant sister:sister correlation greater than spouse
      correlation was observed for MAXCPD only. Single-point sib-pair regression
      analysis provided nominal evidence for linkage of loci to both SRMAXAPD and
      MAXCPD consumption traits, with more significant evidence of linkage to SRMAXAPD
      than to MAXCPD. One genomic region, chr9q21.11, exhibits significant multi-point
      sib-pair regression to SRMAXAPD. CONCLUSION: SRMAXAPD exhibits greater evidence
      for genetic linkage than does MAXCPD in the FHS sample. Four regions of the
      genome exhibiting nominal evidence for linkage to SRMAXAPD in the FHS sample
      correspond to regions of the genome previously identified as linked to alcoholism
      or related traits in the family data set ascertained on individuals affected with
      alcohol dependence known as COGA.

PMID- 14975170
TI  - Multiple genome-wide analyses of smoking behavior in the Framingham Heart Study.
AB  - BACKGROUND: Cigarette smoking behavior may have a genetic basis. We assessed
      evidence for quantitative trait loci (QTLs) affecting the maximum number of
      cigarettes smoked per day, a trait meant to quantify this behavior, using data
      collected over 40 years as part of the Framingham Heart Study's original and
      offspring cohorts. RESULTS: Heritability was estimated to be approximately 21%
      using variance components (VC) methods (SOLAR), while oligogenic linkage and
      segregation analysis based on Bayesian Markov chain Monte Carlo (MCMC) methods
      (LOKI) estimated a mean of two large QTLs contributing approximately 28% and 20%,
      respectively, to the trait's variance. Genome-wide parametric (FASTLINK) and VC
      linkage analyses (SOLAR) revealed several LOD scores greater than 1.0, with peak
      LOD scores using both methods on chromosomes 2, 17, and 20; multi-point MCMC
      methods followed up on these chromosomes. The most robust linkage results were
      for a QTL between 65 and 84 cM on chromosome 20 with signals from multiple sex-
      and age-adjusted analyses including two-point LOD scores of 1.30 (parametric) and
      1.07 (heritability = 0.17, VC) at 70.51 cM, a multi-point LOD score of 1.50
      (heritability = 0.20, VC) at 84 cM, and an intensity ratio of 12.0 (MCMC) at 65
      cM. CONCLUSION: Familial aggregation of the maximum number of cigarettes smoked
      per day was consistent with a genetic component to this behavior, and oligogenic
      segregation analyses using MCMC suggested two important QTLs. Linkage signals on
      chromosome 20 between 65 and 84 cM were seen using multiple analytical methods.
      No linkage result, however, met genome-wide statistical significance criteria,
      and the true relationship between these regions and smoking behavior remains
      unclear.

PMID- 14975171
TI  - A genome-wide scan to identify loci for smoking rate in the Framingham Heart
      Study population.
AB  - BACKGROUND: Although many years of genetic epidemiological studies have
      demonstrated that genetics plays a significant role in determining smoking
      behavior, little information is available on genomic loci or genes affecting
      nicotine dependence. Several susceptibility chromosomal regions for nicotine
      dependence have been reported, but few have received independent confirmation. To
      identify susceptibility loci for nicotine dependence, 313 extended pedigrees
      selected from the Framingham Heart Study population were analyzed by both the
      GENEHUNTER and S.A.G.E. programs. RESULTS: After performing linkage analyses on
      the 313 extended Framingham Heart Study families, the EM Haseman-Elston method
      implemented in GENEHUNTER provided evidence for significant linkage of smoking
      rate to chromosome 11 and suggestive linkage to chromosomes 9, 14, and 17.
      Multipoint sib-pair regression analysis using the SIBPAL program of S.A.G.E. on
      1389 sib pairs that were split from the 313 extended families identified
      suggestive linkage of smoking rate to chromosomes 4, 7, and 17. Of these
      identified positive regions for nicotine dependence, loci on chromosomes 7, 11,
      and 17 were identified by both GENEHUNTER and S.A.G.E. programs. CONCLUSION: Our
      genome-wide scan results on the Framingham Heart Study data provide evidence for
      significant linkage of smoking rate to chromosome 11 and suggestive linkage to
      chromosomes 4, 7, 9, 14, and 17. These findings suggest that some of these
      regions may harbor susceptibility loci for nicotine dependence, and warrant
      further investigation in this and other populations.

PMID- 14975172
TI  - Mapping susceptibility loci for alcohol consumption using number of grams of
      alcohol consumed per day as a phenotype measure.
AB  - BACKGROUND: There is substantial evidence for a significant genetic component to
      the risk for alcoholism. However, susceptibility loci or genes for alcohol
      dependence remain largely unknown. To identify susceptibility loci for alcohol
      dependence, we selected 329 extended families from the Framingham Heart Study
      population in which at least one family member reported alcohol consumption
      during the interview in 1970-1971, and performed genome-wide linkage analyses
      using various analytical methods. RESULTS: Multi-point sib-pair regression
      analysis using the SIBPAL program of S.A.G.E. provided strong evidence for
      linkage of alcohol dependence to chromosomes 9 (p-value < 0.0001) and weak
      evidence to chromosomes 15 and 16 (p-value < 0.005). To confirm these findings,
      we re-analyzed the same data set by various methods implemented in GENEHUNTER and
      found that only one region was significant with a LOD score > 2.0 by the variance
      component method. This region is located on chromosome 9 between markers
      GATA21F05 and GATA81C04. CONCLUSION: Analyses of the Framingham Heart Study
      population provided evidence of genetic susceptibility loci for alcohol
      dependence on chromosomes 9, 15, and 16. The genomic region identified on
      chromosome 9 was particularly interesting because the region has also been
      previously reported to be linked to alcohol dependence in the American Indian
      population by another group.

PMID- 14975173
TI  - Genetic analysis of maximum cigarette-use phenotypes.
AB  - BACKGROUND: Using the Framingham Heart Study data set provided for Genetic
      Analysis Workshop 13, we defined the cigarette-use phenotype M for smokers to be
      the maximum number of cigarettes-per-day (MAXCIG) reported over the longitudinal
      course of the study. Adjustments were made for the significant covariates of
      gender and year of birth, and sib-pair based linkage analysis was performed.
      RESULTS: The primary analyses, in which individuals with MAXCIG = 0 were
      considered to have missing phenotype, resulted in modest linkage evidence, with
      LOD scores over 1 on chromosomes 5, 9, 13, 14, and 22. CONCLUSIONS: While the
      results reported here do not indicate definitive evidence for linkage to specific
      chromosomal regions, future studies may find it useful to include direct
      assessments of maximum and quantitative cigarette use. In defining and analyzing
      quantitative or "maximum use" phenotypes, the choice of how to handle individuals
      with MAXCIG = 0, or alternatively, individuals who are substance-naive, is a
      crucial one for genetic studies of nicotine and other substance use. In this
      study, the linkage results vary greatly depending on whether or not these
      "unexposed" individuals are included in the analyses.

PMID- 14975174
TI  - Genome-wide screen for heavy alcohol consumption.
AB  - BACKGROUND: To find specific genes predisposing to heavy alcohol consumption
      (self-reported consumption of 24 grams or more of alcohol per day among men and
      12 grams or more among women), we studied 330 families collected by the
      Framingham Heart Study made available to participants in the Genetic Analysis
      Workshop 13 (GAW13). RESULTS: Parametric and nonparametric methods of linkage
      analysis were used. No significant evidence of linkage was found; however, weak
      signals were identified in several chromosomal regions, including 1p22, 4q12,
      4q25, and 11q24, which are in the vicinity of those reported in other similar
      studies. CONCLUSION: Our study did not reveal significant evidence of linkage to
      heavy alcohol use; however, we found weak confirmation of studies carried out in
      other populations.

PMID- 14975175
TI  - GOTree Machine (GOTM): a web-based platform for interpreting sets of interesting
      genes using Gene Ontology hierarchies.
AB  - BACKGROUND: Microarray and other high-throughput technologies are producing large
      sets of interesting genes that are difficult to analyze directly. Bioinformatics
      tools are needed to interpret the functional information in the gene sets.
      RESULTS: We have created a web-based tool for data analysis and data
      visualization for sets of genes called GOTree Machine (GOTM). This tool was
      originally intended to analyze sets of co-regulated genes identified from
      microarray analysis but is adaptable for use with other gene sets from other high
      throughput analyses. GOTree Machine generates a GOTree, a tree-like structure to
      navigate the Gene Ontology Directed Acyclic Graph for input gene sets. This
      system provides user friendly data navigation and visualization. Statistical
      analysis helps users to identify the most important Gene Ontology categories for
      the input gene sets and suggests biological areas that warrant further study.
      GOTree Machine is available online at http://genereg.ornl.gov/gotm/. CONCLUSION:
      GOTree Machine has a broad application in functional genomic, proteomic and other
      high-throughput methods that generate large sets of interesting genes; its
      primary purpose is to help users sort for interesting patterns in gene sets.

PMID- 14975176
TI  - Effects of oral anticoagulation with various INR levels in deep vein thrombosis
      cases.
AB  - AIM: In order to avoid the complications associated with thromboembolic disease,
      patients with this condition typically are placed on long-term anticoagulant
      therapy. This report compares bleeding complications in this patient population
      by level of achieved INR. MATERIALS AND METHODS: During the 6-year period between
      January 1997 and January 2003, 386 patients with venous thromboembolism of the
      lower extremities were admitted to the Cardiovascular Surgery Outpatient Clinic
      of Alsancak State Hospital. Of the 386 patients, 198 (51.2%) were women, and the
      average age was 52.3 years. All diagnoses of venous thromboembolism were
      confirmed by means of Doppler ultrasonography. Further investigation showed
      occult neoplasms in 22 (5.6%) of the cases. We excluded the patients with occult
      disease, and the remaining 364 constituted our study population. RESULTS: Oral
      anticoagulation was standardized at 6 months' duration in all cases. We divided
      the patients into two groups. Group I consisted of 192 patients (52.7%) with INR
      values between 1.9 and 2.5; Group II comprised 172 patients with INR values
      between 2.6 and 3.5. Complications in each group were assessed and compared. The
      minor hemorrhage rate was 1.04% in Group I and 4.06% in Group II. The major
      hemorrhage rate was also 1.04% in Group I and was 6.3% in Group II. We determined
      that the complication rates for both minor and major hemorrhage were significant
      in patients with INR values above 2.5. CONCLUSION: Oral anticoagulation must be
      followed closely in patients with venous thromboembolism. Higher INR levels are
      associated with significant increases in hemorrhage and associated complications.
      INR values of 2.0 to 2.5 are sufficient for long-term anticoagulant therapy,
      ensuring ideal anticoagulation levels and minimizing the complication rate.

PMID- 14975177
TI  - Hypotonicity-induced ATP release is potentiated by intracellular Ca2+ and cyclic
      AMP in cultured human bronchial cells.
AB  - We have examined the cultured human bronchial epithelial cells (16HBE) to learn
      if changes in Cl(-) concentration or osmolality stimulate the cells to release
      ATP and to determine whether its release is cyclic AMP (cAMP)- and/or Ca(2+)
      dependent by using the luciferin-luciferase luminometric assay. In a control
      solution (290 mosmol kg H(2)O(-1)), the external ATP concentration and the rate
      of ATP release were 0.52 +/- 0.20 nM and 0.036 +/- 0.034 pmol min(-1),
      respectively. Upon hypotonicity (205 mosmol kg H(2)O(-1)), they increased to 7.0
      +/- 1.3 nM and 3.1 +/- 0.6 pmol min(-1), respectively, at 6 min, then decreased.
      At the peak, the rate of ATP release is estimated to be 6.2x10(4) ATP molecules
      s(-1) per cell. An accumulation of the released ATP for the initial 10 min
      increased significantly (p < 0.005) by 71.5% in the presence of forskolin (10
      microM), adenylyl cyclase activator, however, it was abolished (p < 0.001) by
      pretreatment with BAPTA-AM (25 microM), a membrane permeable Ca(2+) chelator. On
      the other hand, neither low Cl(2-) (75 mM, isotonic) nor hypertonicity (+NaCl or
      +mannitol, 500 mosmol kg H(2)O(-1)) could significantly increase the ATP release.
      Further, forskolin or ionomycin (a Ca(2+) ionophore) or, both, failed to
      stimulate ATP release under the isotonic condition. In conclusion, first,
      hypertonicity and changes in Cl(-) concentrations are not effective signals for
      the ATP release; second, hypotonicity-induced ATP release is potentiated by the
      level of intracellular Ca(2+) and cAMP; and third, a biphasic increase in ATP
      release and its low rate at the peak support the hypothesis that ATP is released
      through a non-conducting pathway model, such as exocytosis, or through a volume
      dependent, ATP-conductive anion channel.

PMID- 14975178
TI  - The effect of muscle contraction velocity on cardiorespiratory responses to
      repetitive isokinetic exercise in humans.
AB  - We investigated the effect of muscle contraction velocity on cardiorespiratory
      responses during exercise. Eight males (23 +/- 2 years, 175 +/- 5 cm, 64 +/- 6
      kg, mean +/- SD) performed 3-min repetitive one-leg extension exercises at
      various angular velocities (30, 60, 120, and 240 deg/s) with a controlled
      relaxation interval, relatively constant (duty cycle = 1:1, A trial) and
      absolutely constant (relaxation time = 0.75 s, B trial) at a total work of 2,100
      2,400 J in an isokinetic mode, using a Cybex II dynamometer. We measured heart
      rate (HR), mean blood pressure (MAP), minute ventilation (Vdot;E), and oxygen
      uptake (Vdot;O(2)) during the exercise. The angular velocity significantly
      affected the increase in HR, MAP, Vdot;E, and Vdot;O(2) at the end of exercise
      from resting in both A and B trials (e.g., MAP: 12 +/- 2, 10 +/- 2, 11 +/- 2, and
      18 +/- 2 mmHg in the A trial). The result suggests that muscle contraction
      velocity affects cardiorespiratory responses during repetitive isokinetic
      exercise.

PMID- 14975179
TI  - Age-dependent changes in the regulatory roles of nitric oxide and vasodilator
      prostanoids on the mechanical activities of isolated rabbit spinal arterioles.
AB  - The developmental changes in acetylcholine (ACh)-induced vasodilator response in
      isolated rabbit spinal arterioles were investigated with special reference to
      endogenous nitric oxide (NO) and vasodilator prostaglandins. Spinal arterioles
      from juvenile (1-3 months) and adult (12-14 months) Japanese white rabbits were
      dissected, cannulated, and perfused. In both age groups, ACh produced a
      comparable vasodilation of the arterioles preconstricted with KCl (20-40 mM). In
      juveniles, a major part of the ACh-induced vasodilation was eliminated by the
      cyclo-oxygenase inhibitor indomethacin (10 microM), whereas the effect of the NO
      synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 30 microM) was
      smaller. In contrast, L-NAME completely eliminated the ACh-induced vasodilation
      in the adult group, which was partially restored with additional treatment with L
      arginine (1 mM). Vasodilations induced by isocarbacyclin (a prostacyclin
      analogue) and cilostazol (a cAMP-phosphodiesterase inhibitor) was attenuated in
      the adult, whereas that induced by sodium nitroprusside was unaltered. These
      results suggest that the mechanisms of ACh-induced vasodilation of rabbit spinal
      arterioles change with the development: prostanoid-associated in juveniles and NO
      associated in the adult. Such age-related modulation of the mediator roles of
      prostanoids and NO might represent an increase in NO production and a decreased
      sensitivity of the vascular smooth muscle to cAMP-mediated responses with age.

PMID- 14975180
TI  - Leukocyte behavior in angiogenic vessels is affected by tumor-derived nitric
      oxide.
AB  - Recent studies indicate a possible role of nitric oxide (NO) in regulating
      leukocyte-endothelial cell interactions, which plays a key role in the tumor
      immunity. The purpose of the present study is aimed to observe the tumor
      hemodynamics intravitally and to clarify the effect of NO on tumor
      microcirculation by means of a real-time confocal laser-scanning microscope using
      NO-reactive indicators. Visualization of localization of NO and the leukocyte
      behavior was made in the mesenteric microvessels of an experimental tumor model
      rat. Production of NO was clearly visualized along the endothelium of the tumor
      free rats, but scarcely found in the newly formed tumor microvessels. A higher
      level of NO production was observed in a solid tumor region, where a more marked
      decrease in the leukocyte-endothelial cell interactions was observed. Local
      administration of a NO synthase (NOS) inhibitor increased leukocyte adhesion.
      This indicates that tumor-derived NOS creates the tumor specific microenvironment
      of the immature angiogenic tumor vessels, thereby modulating leukocyte behavior.

PMID- 14975181
TI  - The redox states of serum and synovial fluid of patients with temporomandibular
      joint disorders.
AB  - The redox states of albumin in serum and synovial fluid (SF) were analyzed in 35
      female patients with temporomandibular joint disorders and 9 asymptomatic female
      healthy volunteers by high-performance liquid chromatographic (HPLC) analysis.
      Human serum albumin (HSA) is divided by HPLC analysis into three fractions:
      mercaptalbumin (HMA, reduced form) and nonmercaptalbumin (HNA-1 and HNA-2,
      oxidized forms). It was found that the characterized values of albumin in SF of
      patients with the disorders were the fraction of HMA (f (HMA), 65.8 +/- 9.1%),
      the fraction of HNA-1 (f (HNA-1), 31.3 +/- 8.8%), and the fraction of HNA-2 (f
      (HNA-2), 2.9 +/- 0.9%), respectively, and similarly the values of albumin in
      serum of same subjects were f (HMA), 79.4 +/- 4.0%; f (HNA-1), 18.7 +/- 3.8%; and
      f (HNA-2), 1.9 +/- 0.5%. The HNA fractions in SF were significantly higher than
      those in serum (p < 0.0001). The SF of patients and even control showed more
      oxidative condition compared with sera of the same subjects. Each fraction of SF
      showed significant difference in control (p < 0.05), and greater significance in
      patients (p < 0.0001). Furthermore, the HNA-2 fraction (f (HNA-2), 2.9 +/- 0.9%)
      in SF of the patients with temporomandibular joint disorders revealed a
      significantly higher value (p < 0.01) than that (f (HNA-2), 1.7 +/- 0.3%) of
      controls. These findings suggested that SF of the temporomandibular joint is more
      locally oxidized than serum; thus oxidative factors are concerned in the
      pathogenesis of the temporomandibular joint disorders. It was also suggested that
      synovial albumin may play a scavenging role against the intraarticular oxidative
      stress.

PMID- 14975182
TI  - Ischemia-induced enhancement of CFTR expression on the plasma membrane in
      neonatal rat ventricular myocytes.
AB  - Pathophysiological functions of cardiac cystic fibrosis transmembrane conductance
      regulator (cCFTR) in ischemia are not well known. Using neonatal rat ventricular
      cardiomyocytes in primary culture in this study, we thus examined whether the
      CFTR protein is expressed and is functioning as a cAMP-activated anion channel on
      the plasma membrane under ischemic conditions. After the cells were subjected to
      simulated ischemia (O(2) and glucose deprivation), an up-regulation of the CFTR
      expression was transiently observed in the membrane fraction by Western blot. A
      peak expression of mature CFTR protein was found at 3 h of ischemia, and
      thereafter the signal diminished gradually. In contrast, the results of Northern
      blot indicated that the expression level of CFTR mRNA changed little until 3 h of
      ischemia, whereas the level slightly decreased after 8 h of ischemia. An
      immunohistochemical examination showed, in agreement with the results of Western
      blot analysis, that the expression of CFTR protein on the plasma membrane became
      most prominent at 3 h of ischemia, whereas the plasmalemmal CFTR signal was
      markedly reduced after 8 h of ischemia. Whole-cell recordings showed that the
      cardiomyocytes responded to cAMP with an activation of time- and voltage
      independent currents that contained an anion-selective component sensitive to
      CFTR Cl(-) channel blockers (NPPB and glibenclamide) but not to a stilbene
      derivative conventional Cl(-) channel blocker (SITS). This cAMP-activated Cl(-)
      channel current was found to be enhanced after an application of ischemic stress
      for 3 to 4 h. These findings indicate that a plasmalemmal expression of CFTR is
      transiently enhanced under glucose-free hypoxic conditions presumably because of
      a posttranslational control.

PMID- 14975183
TI  - Blocking NF-kappaB activation may be an effective strategy in the fever therapy.
AB  - Lipopolysaccharide (LPS) stimulates peripheral mononuclear cells (PBMC) to
      synthesize or release pyrogenic cytokines, including interleukin-1beta (IL
      1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha). Nuclear factor-kappa B
      (NF-kappaB) influences inflammatory responses through the regulation of genes
      encoding cytokines. In the present study, experiments were carried out to
      determine whether an inhibition of NF-kappaB mechanisms causes an inhibition of
      pyrogenic cytokine synthesis or release from PBMC and results in antipyresis.
      Intravenous administration of the supernatant fluids obtained from the human PBMC
      incubated with LPS caused feverlike hyperthermia in rabbits. The febrile
      responses were in parallel with the levels of IL-1beta, IL-6, and TNF-alpha in
      supernatant fluids. Both the fever and the increased levels of these cytokines in
      supernatant fluids were decreased by incubating LPS-PBMC with NF-kappaB
      inhibitors, including pyrrolidine dithiocarbamate, sodium pyrithione, N-acetyl
      cysteine, and curcumin. Moreover, an intravenous administration of LPS (0.5-2
      microg/kg) produced dose-dependent fever in the rabbits. The fevers were in
      parallel with the levels of IL-1beta, IL-6, and TNF-alpha in rabbit serum. A
      pretreatment of rabbits with an intravenous injection of pyrrolidine
      dithiocarbamate, sodium pryithione, N-acetyl-cysteine, or curcumin 1 h before the
      intravenous administration of LPS significantly attenuated the LPS-induced fever
      and/or increased levels of these cytokines in the serum of rabbits. Furthermore,
      pretreatment with an intravenous dose of anti-IL-1beta, anti-IL-6, or anti-TNF
      alpha monoclonal antibody significantly attenuated the fever induced by the
      intravenous injection of LPS in rabbits. The antipyretic effects exerted by anti
      L-1beta monoclonal antibody were greater than those exerted by anti-L-6 or anti
      NF-alpha monoclonal antibody. The data indicate that NF-kappaB activation
      correlates with an LPS-induced synthesis or a release of cytokines (in
      particular, IL-1beta) from PBMC and triggers fever. Blocking NF-kappaB mechanisms
      in the PBMC with NF-kappaB inhibitors may be an effective strategy in the fever
      therapy.

PMID- 14975184
TI  - Cardiopulmonary hemodynamics of blue-sheep, Pseudois nayaur, as high-altitude
      adapted mammals.
AB  - The blue-sheep, pika, and yak live in the Tibetan highlands at an altitude of
      6,100 m and are typical mammals adapted to high-altitudes. These animals have a
      long history of habitation at high-altitudes and are considered to be "animals
      completely adapted to high-altitudes" because of their physiological and
      morphological traits that are well adapted to high-altitude environments. To
      evaluate the physiological characteristics of high-altitude adaptation in the
      blue-sheep, changes in the pulmonary hemodynamics during exposure to simulated
      altitudes at 0, 2,300, and 4,500 m were examined by means of a climatic chamber
      in Qinghai Province, China (altitude 2,300 m). Seven blue-sheep inhabiting the
      mountains (3,000 m) of Qinghai Province, China, were compared with 5 pigs raised
      in the same area as controls. The primary items of measurement were the body
      weight (BW), systemic arterial pressure (Psa), pulmonary artery pressure (Ppa),
      hematocrit (Ht), left ventricular weight (LVW), right ventricular weight (RVW),
      and blood gas profile. The principal findings of this study are: (1) Ht, an index
      of right ventricular hypertrophy (RVW/LVW), and oxygen consumption (Vdot;O(2))
      were significantly lower in the blue sheep compared with the pigs; (2) When the
      animals were exposed to simulated-altitudes at 0, 2,300, and 4,500 m, Ppa
      increased significantly in tandem with altitude elevation in both species, but
      the increases were significantly smaller in the blue-sheep; and (3) Ppa/Psa, an
      index of the right ventricular load, increased with the altitude in both species,
      but the increases were smaller in the blue sheep. From these observations, low Ht
      and RVW/LVW and significant attenuation of hypoxic pulmonary vasoconstriction
      (HPV) in the blue-sheep is considered to be characteristics of animals completely
      adapted to high-altitudes, such as the pika.

PMID- 14975185
TI  - Video-imaging visualization of blood flow dynamics in early chick embryo.
AB  - The blood flow dynamics in the early chick embryo were visualized by using a
      video-imaging method without invasion to the circulatory system. The movement of
      juvenile blood cells in the dorsal aorta was tracked and the flow velocity of
      blood cells calculated by using an image processor and a computer.

PMID- 14975186
TI  - Viral interleukin-10-engineered autologous hematopoietic stem cell therapy: a
      novel gene therapy approach to prevent graft rejection.
AB  - The Epstein-Barr virus-encoded protein BCRF1 (viral interleukin [vIL]-10) is a
      biologically active homologue of cellular interleukin (IL)-10. In this study, a
      novel gene therapy approach to prolong allograft survival was designed.
      Autologous (syngeneic) hematopoietic progenitor/stem cell-enriched (HSC; lineage(
      ve)) population derived from CBA/J mouse bone marrow were transduced with
      retrovirus encoding vIL-10 gene (vIL-10-HSC), ex vivo; vIL-10-HSC were injected
      (4-6 x 10(6) cells intravenously) into lethally (9.5 Gy) or sublethally (4 Gy)
      irradiated CBA/J mice. Six weeks after vIL-10-HSC administration, vascular
      heterotopic heart (C57BL/6) transplantation was performed. Ex vivo, the vIL-10
      HSC produced 5.4 +/- 0.5 ng of vIL-10 protein/2 x 10(5) cells per 24 hr. In vivo,
      serum vIL-10 production was 187 +/- 205 pg/ml during 3-10 weeks after vIL-10-HSC
      administration. Cardiac allograft survival was prolonged (p < 0.004) in lethally
      (71 +/- 40 days) and sublethally (114 +/- 15 days) irradiated mice that received
      vIL-10-HSC compared to controls that received unengineered (UE) HSC or vector DNA
      engineered HSC (12-16 days). However, secondary skin graft (C57BL/6) survival was
      not prolonged in cardiac allograft-tolerant animals. In the vIL-10-HSC
      administered group, graft histopathology demonstrated mild arteritis/venulitis
      (grade 0.7) and rejection (grade 1.0). Intragraft expression of costimulatory
      molecules (B7.1, B7.2), cytokines (IL-2, IL-4, mIL-10, interferon [IFN]-gamma),
      and inducible nitric oxide synthase (iNOS) molecules was markedly lower in vIL-10
      HSC-treated tolerant grafts that survived more than 100 days compared to vector
      DNA-HSC- or UE-HSC-treated controls. Furthermore, T lymphocytes derived from vIL
      10-HSC-treated tolerant recipients demonstrated hyporeactivity to donor antigens
      in mixed lymphocyte cultures. Administration of autologous vIL-10-engineered HSC
      prior to organ transplantation prolonged cardiac allograft survival
      significantly.

PMID- 14975187
TI  - Sustained improvement of muscle function one year after full-length dystrophin
      gene transfer into mdx mice by a gutted helper-dependent adenoviral vector.
AB  - Dystrophin gene transfer using helper-dependent adenoviral vectors (HDAd) deleted
      of all viral genes is a promising option to treat muscles in Duchenne muscular
      dystrophy (DMD). Previously, we reported high-level dystrophin expression and
      functional correction of dystrophin-deficient (mdx) mouse muscle 60 days after
      gene transfer with an HDAd encoding two full-length murine dystrophin cDNAs
      (referred to as HDCBDysM). In the present study, we tested the long-term efficacy
      of HDCBDysM by examining muscle contractility parameters and the stability of
      dystrophin expression 1 year after injection into neonatal mdx muscles. At this
      point, HDCBDysM-treated muscles averaged 52% dystrophin-positive fibers. Treated
      muscles also displayed significantly greater isometric force production as well
      as greater resistance to the force deficits and damage caused by eccentric
      contractions. The level of protection against eccentric contraction-induced force
      deficits correlated with the percentage of dystrophin-positive fibers.
      Furthermore, HDCBDysM treatment restored the dystrophin-glycoprotein complex
      (DGC) to the sarcolemma and improved other aspects of mdx muscle histopathology
      examined (central nucleation, muscle hypertrophy, and mononuclear [phagocytic]
      cell infiltration). These improvements occurred despite the induction of a
      humoral response against murine dystrophin. Our results indicate that major
      therapeutic benefits of HDCBDysM are maintained for a long period of the animals'
      lifespan and suggest that HDCBDys holds promise for treating DMD by gene therapy.

PMID- 14975188
TI  - A single lentivirus vector mediates doxycycline-regulated expression of
      transgenes in the brain.
AB  - A single lentivirus vector allowing doxycycline-regulated expression of
      transgenes in the brain was generated by incorporating the tetracycline (Tet)
      dependent regulatory system into the backbone of the vector. Two distinct
      expression cassettes were inserted upstream and downstream from the central Flap
      sequence that provides for enhanced transduction of nondividing cells. The first
      cassette was used to express the transgene under the control of the Tet-dependent
      minimal cytomegalovirus promoter. The second cassette was employed to express
      constitutively the Tet-dependent transactivator rtTA2-M2, which activates the Tet
      dependent promoter after binding of doxycycline (Tet-on system). Vectors carrying
      luciferase and tyrosine hydroxylase as the transgene were constructed, tested in
      astroglia-rich primary cultures, and injected into the striata of rats. The
      constructs allowed in vitro and in vivo robust expression of the transgene that
      could be regulated over two orders of magnitude by the addition and withdrawal of
      doxycycline. The vector may thus be useful for many applications in gene therapy
      research, including the development of a therapeutic protocol for the treatment
      of Parkinson's disease based on the restoration of regulated dopamine production.

PMID- 14975189
TI  - Vaccination with a DNA vaccine encoding herpes simplex virus type 1 VP22 linked
      to antigen generates long-term antigen-specific CD8-positive memory T cells and
      protective immunity.
AB  - Intradermal vaccination with DNA encoding herpes simplex virus type 1 (HSV-1)
      VP22 linked to antigen leads to spread of antigen within the epithelium and
      results in enhanced antigen-specific CD8+ T cell immune responses in vaccinated
      mice. In this study, we characterized the number of antigen-expressing dendritic
      cells (DCs) in the draining lymph nodes of vaccinated mice and determined whether
      the linkage of VP22 to antigen would influence the ability of antigen-expressing
      DCs to activate antigen-specific CD8+ T cells in vivo. Vaccination with DNA
      encoding HSV-1 VP22 linked to human papillomavirus type 16 E7 antigen generated
      more antigen-expressing DCs in the draining lymph nodes of vaccinated mice than
      E7 alone. In addition, the linkage of VP22 to E7 improved the MHC class I
      presentation of E7 in transfected DCs and led to enhanced activation of E7
      specific CD8+ T cells. We also observed that vaccination with DNA encoding VP22
      linked to E7 generated more E7-specific CD8+ memory T cells, and enhanced long
      term protective antitumor immunity against an E7-expressing tumor in vaccinated
      mice compared with vaccination with DNA encoding E7 alone. Thus, administration
      of DNA encoding VP22 linked to antigen represents a plausible approach for the
      development of protective DNA vaccines.

PMID- 14975190
TI  - Helper-dependent adenoviral vectors containing modified fiber for improved
      transduction of developing and mature muscle cells.
AB  - Adenoviruses (Ads) have shown great utility as vectors for the delivery of genes
      to mammalian cells, partly because of their ability to infect a wide range of
      different cell types independent of the replicative state of the cell. However,
      Ads do not transduce mature muscle efficiently because of low levels of the
      natural viral primary receptor, the coxsackie virus and adenovirus receptor, on
      the surface of adult muscle cells. In this study, we have addressed whether
      incorporation of polylysine [p(K)] or arginine-glycine-aspartic acid (RGD) placed
      in the H-I loop of the adenoviral fiber protein can improve helper-dependent Ad
      vector (hdAd) transduction of mature muscle cells. We show that incorporation of
      the p(K) motif into the fiber of early region 1 (E1)-deleted Ad results in
      enhanced transduction of undifferentiated and differentiated C2C12 cells relative
      to a virus, containing a wild-type fiber (12- and 21-fold enhancement,
      respectively). Incorporation of the RGD motif resulted in only a 60-70% increase
      in transduction efficiency in these cells. The two fiber modifications were then
      incorporated into helper viruses for use in the Cre-lox system for generating
      hdAd, and the resulting retargeted Ad vectors, which encoded the beta
      galactosidase reporter gene (beta-Gal), demonstrated enhanced transduction of
      C2C12 cells in culture. Although hdAdpK also showed enhanced infection of mature
      mouse muscle in vivo, hdAdRGD did not. All hdAd vectors elicited only minor anti
      Ad immune responses, compared with an E1-deleted control vector, but each vector
      elicited strong anti-beta-Gal immunoreactivity. Our results demonstrate that hdAd
      with modified cell tropism can be generated efficiently and, in the case of
      polylysine-modified hdAd, can lead to improved transduction of adult muscle cells
      in vivo.

PMID- 14975191
TI  - Gene therapy of collagen-induced arthritis by electrotransfer of human tumor
      necrosis factor-alpha soluble receptor I variants.
AB  - Electrotransfer is a simple and efficient strategy of nonviral gene delivery. We
      have used this method to deliver plasmids encoding three human tumor necrosis
      factor-alpha soluble receptor I variants (hTNFR-Is) a monomeric hTNFR-Is, a
      chimeric hTNFR-Is/mIgG1, and a dimeric (hTNFR-Is)(2) form. Electrotransfer
      parameters were studied and because anti-TNF strategies have proven efficient for
      the treatment of rheumatoid arthritis in clinics, we used a collagen-induced
      arthritis (CIA) mouse model to assess the efficacy of our constructs in the
      treatment of the disease. All proteins were proven bioactive, both in vitro and
      ex vivo. Plasmid intramuscular electrotransfer in mice resulted in a local
      expression of the three variants for at least 6 months; systemic expression
      lasted also more than 6 months for the hTNFR-Is/mIgG1 form, while it was shorter
      for the two other forms. This expression was plasmid dose-dependent.
      Electrotransfer of 50 microg of hTNFR-Is/mIgG1 at the onset of a CIA induced a
      clear-cut decrease in both clinical and histologic signs of the disease; the
      dimeric form also showed some efficacy. Moreover, the long-lasting protective
      effect was observed for more than 5 weeks. Comparison of this electrotransfer
      approach with repeated recombinant protein (etanercept) injections highlighted
      the potential practical interest of gene therapy approach for CIA, which leads to
      sustained therapeutic effect after single treatment. These results show that
      electrotransfer may be a useful method to deliver cytokine or anticytokine
      therapy in rheumatoid arthritis and also illustrate the potentiality of plasmid
      intramuscular electrotransfer for the rapid screening and assessment of different
      variant forms of secreted proteins.

PMID- 14975192
TI  - Hepatitis B virus-based vectors allow the elimination of viral gene expression
      and the insertion of foreign promoters.
AB  - It has recently been shown that hepatitis B virus (HBV)-based vectors are
      suitable for a hepatocyte specific gene transfer. As candidate vectors for gene
      therapy, however, they should no longer express any viral gene products. In
      addition, the insertion of promoters that do not originate from HBV is needed to
      allow a variation of the level of gene expression. Furthermore, production of
      high-titer stocks is required. To eliminate viral gene expression, we knocked out
      all HBV open reading frames (ORFs) in the transfer construct used to express
      recombinant HBV RNA. To minimize the chance of homologous recombination, we
      generated an improved helper construct. With these constructs, recombinant
      viruses containing single or combined knockouts of the viral ORFs were produced
      at titers equal to wild-type HBV produced in parallel. We identified a site in
      the HBV genome that allows insertion of foreign promoter elements without
      interfering with maturation of infectious HBV particles. Successful gene transfer
      was demonstrated on infection of primary human hepatocytes using recombinant HBV
      in which all viral ORFs were knocked out and a foreign promoter controlled
      transgene expression. These improvements represent a major step toward the
      development of HBV vectors as candidates for human gene therapy.

PMID- 14975194
TI  - Evaluation of plasmid DNA removal from lentiviral vectors by benzonase treatment.
AB  - To improve the purity of lentiviral vector supernatants for clinical studies we
      have evaluated plasmid DNA removal from lentiviral vectors and also the extent of
      plasmid DNA associated with transduced CD34 cells in an ex vivo transduction
      protocol. Optimal conditions of plasmid DNA removal by benzonase treatment were
      established by varying the temperature, time, and benzonase concentrations in the
      reaction mix and were determined to be 50 units of benzonase per milliliter of
      vector supernatant at 37 degrees C, for 15 min. No plasmid DNA was detected,
      suggesting efficient plasmid degradation was achieved under these experimental
      conditions. The infectious titer of benzonase-treated lentiviral vector (RRL-CMV
      GFP) was nearly identical to the titer of untreated vector (2.3 +/- 0.3 x 10(6)
      transduction units per milliliter (TU/ml) and 2.7 +/- 0.3 x 10(6) TU/ml,
      respectively). Analysis of plasmid DNA in concentrated lentiviral vectors shows
      that concentration substantially decreases the amount of DNA per TU. Analysis of
      the extent of plasmid DNA associated with transduced CD34 cells in an ex vivo
      transduction protocol suggests that a minimal amount of plasmid is transferred to
      transduced cells if the vector supernatant was not previously treated with
      benzonase. In conclusion, benzonase treatment is effective in eliminating plasmid
      DNA from vector supernatants and treatment does not affect infectious titers.
      However, because there is minimal transfer of plasmid DNA to transduced cells
      under ex vivo transduction conditions, DNA removal from lentiviral vectors may
      not be essential for all ex vivo clinical applications.

PMID- 14975193
TI  - Transduction of human islets with pseudotyped lentiviral vectors.
AB  - Type I diabetes is caused by an autoimmune-mediated elimination of insulin
      secreting pancreatic islets. Genetic modification of islets offers a powerful
      molecular tool for improving our understanding of islet biology. Moreover,
      efficient genetic engineering of islets could allow for evaluation of new
      strategies aimed at preventing islet destruction. The present study evaluated the
      ability of a human immunodeficiency virus (HIV)-based lentiviral vector
      pseudotyped with various viral envelopes to target human islets ex vivo, with the
      goal of improving efficiency while minimizing toxicity. Transfer of the enhanced
      green fluorescent protein reporter gene in human islets was first evaluated with
      an HIV-based vector pseudotyped with the vesicular stomatitis virus (VSV), murine
      leukemia virus, Ebola, rabies, Mokola, or lymphocytic choriomeningitis virus
      (LCMV) envelope glycoprotein to optimize transduction efficiency. Results
      indicated that LCMV-pseudotyped vector transduced insulin-secreting beta cells
      with the highest efficiency. Moreover, toxicity associated with transduction of
      islets was found to be lower with LCMV-pseudotyped vector than with VSV-G
      pseudotyped vector, the second most efficient vector for islet transduction.
      Overall, our study describes an improved methodology for achieving safe and
      efficient gene transfer into cells of human islets.

PMID- 14975195
TI  - A long-term follow-up study of serum lipid levels and coronary heart disease in
      the elderly.
AB  - BACKGROUND: It is still controversial whether or not the correlation between
      lipid abnormality and coronary heart disease (CHD) becomes weaker in the elderly,
      and whether patients above 80 years old still benefit from lipid management for
      the secondary prevention of CHD. The purpose of this study is to assess the
      correlation between hyperlipidemia and the risk of CHD events in the elderly, and
      to determine if it is appropriate to use lipid-lowering drugs in those aged above
      80, as prescribed by the recommended guidelines for lipid management. METHODS:
      One thousand two hundred and eleven retirees, mainly males (92%), aged 70 +/- 9
      years, were enrolled in this study. Lifestyle habits and medical history were
      recorded via questionnaires. During the period 1986 - 2000, all subjects
      participated in an annual physical examination with a blood chemistry survey. The
      mean follow-up period was 11.2 years. Subjects with incidental illnesses,
      especially cardiovascular diseases, were diagnosed or treated promptly. Serum
      lipid parameters, including total cholesterol (TC), low and high-density
      lipoprotein cholesterol (LDL-C and HDL-C) and triglyceride (TG) levels were
      analyzed according to standardization of lipid and lipoprotein measurements. The
      association between lipid levels and the prevalence of acute myocardial
      infarction (AMI) or coronary death was analyzed statistically. RESULTS: Lipid
      abnormalities occurred in 2/3 of the 1211 subjects. The most common lipid
      disorder was high TC and high LDL-C, which was much more prevalent than high TG.
      Among the subjects, 51.6% had TC levels above 5.2 mmol/L. Mean TC and LDL-C
      reached peak levels in the 65 - 74 age group without significant decrease until
      ages over 90. The cumulative total number of deaths due to various causes was 397
      in the 15-year follow-up period, with the mortality rate in the high lipid group
      slightly lower than that in the normal lipid group (30.6% vs 35.3%), although the
      difference was not significant (P = 0.1931). However, there were more cases of
      coronary death in the high lipid group than in the normal lipid group (7.9% vs
      4.6%, P = 0.0045). When examining AMI survivors, more AMI cases were found in the
      high lipid group than in the low lipid group (20.9% vs 11.4%, P < 0.0001). The
      cumulative number of coronary deaths was 89 (with 88 cases above age 70), and the
      total number of CHD cases was 214 (17.7% of the whole group). Logistic regression
      analysis reveals that age, hypertension, LDL-C, and HDL-C are important risk
      factors for CHD. Lifestyle changes were common, but only 45% of the
      hyperlipidemic cases received drug treatment. Statins were commonly used only in
      recent years. CONCLUSION: The above results show that high TC and LDL-C levels
      are correlated with a high CHD risk even in people over 80. For elderly patients
      with clinical CHD and an aggregation of CHD risk factors, cholesterol-lowering
      therapy might be considered if the general health of the patient makes this
      permissible.

PMID- 14975196
TI  - Radiofrequency catheter ablation at the left coronary cusp in treatment of
      repetitive monomorphic tachycardia of the left ventricular outflow tract.
AB  - BACKGROUND: The aim of this study was to clarify the electrocardiographic
      characteristics of repetitive monomorphic ventricular tachycardia (RMVT)
      originating from the left ventricular outflow tract, and to describe the results
      of treatment with radiofrequency catheter ablation (RFCA). METHODS: Routine 12
      lead surface electrocardiography and electrophysiological studies were performed
      on 11 RMVT patients with no organic heart disease, who were subsequently treated
      with RFCA directed at targets identified by pace mapping. RESULTS: The surface
      electrocardiogram QRS characteristics of RMVT included an atypical left bundle
      branch block and right axis deviation, with a low amplitude "rs" or "rS" pattern
      in lead I, an "rS" or "RS" pattern in V1, and a precordial R wave transition zone
      in V2 or V3. In 1 patient, a small S wave was observed in V5. Using pace mapping
      techniques, we selected the left coronary cusp as the ablation target. RMVT was
      eliminated in all 11 patients immediately after radiofrequency energy delivered.
      During a follow-up of 13 +/- 7 months, RMVT recurred in only 1 patient.
      CONCLUSION: RMVT originating from the left ventricular outflow tract has specific
      electrocardiographic characteristics, and can be successfully and safely cured
      using RFCA directed at the left coronary cusp.

PMID- 14975197
TI  - Polymorphism K469E of intercellular adhesion molecule-1 gene and restenosis after
      coronary stenting in Chinese patients.
AB  - BACKGROUND: Inflammation is a major cause of restenosis after coronary stenting.
      Intercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule that
      plays a key role in the tight adhesion between leukocytes and vascular
      endothelium. The object of this study was to investigate the association between
      the K469E polymorphism of the ICAM-1 gene and restenosis after coronary stenting
      in North Chinese population. METHODS: The ICAM-1 K469E polymorphism was genotyped
      using polymerase chain reaction-restriction fragment length polymorphism method
      in 124 patients who had undergone coronary stenting and coronary angiography at
      least 3 months earlier. Information on clinical risk factors and procedure
      related data were also collected. RESULTS: Of 124 enrolled patients in total,
      there were 72 cases of in-stent restenosis. The restenosis rate in this
      population was 58.1%. The frequencies of the three possible genotypes of the ICAM
      1 K469E polymorphism were: KK genotype 50.8%, EE genotype 41.9%, and EK genotype
      41.9%. Among restenosis patients, the frequency of the KK genotype was 58.3% and
      the frequency of E allele carriers was 41.7%. Among non-restenosis patients, the
      frequency of the KK genotype was 40.4%, and the frequency of E allele carriers
      was 59.6%. The distribution of these two genotype groups between restenosis and
      non-restenosis patients was significantly different (P = 0.049). Using
      multivariate logistic regression, the difference between the two groups was more
      apparent. The odds ratio of KK homozygotes vs E allele carriers was 2.6, with 95%
      confidence interval 1.2 - 5.8 (P = 0.018). After grading of risk factors, we
      found that the KK genotype was a stronger predictor of in-stent restenosis in
      obesity or hyperlipemia patients, with an odds ratio of 9.3 and 3.7, respectively
      (P < 0.05). CONCLUSION: In our study population, KK homozygotes of the ICAM-1
      codon 469 mutation had a higher risk of restenosis after coronary stenting,
      especially in the case of obese or hyperlipemia patients.

PMID- 14975198
TI  - Prognostic value of Doppler transmitral filling patterns in patients with chronic
      heart failure.
AB  - BACKGROUND: Chronic heart failure is a significant cause of cardiovascular
      morbidity and mortality. This study tested the hypothesis that restrictive
      filling pattern may provide useful prognostic data for identifying patients with
      chronic heart failure at high risk of all-cause cardiac death. METHODS: Ninety
      patients with chronic heart failure [70 men and 20 women, mean age (58.1 +/-
      11.6) years] were investigated and followed for (18.8 +/- 7.9) months. During
      this period, 14 patients died of progressive pump failure, 12 patients underwent
      heart transplantation, 5 patients died suddenly, and 2 patients died of acute
      myocardial infarction. A new criterion, the restrictive filling index (RFI), was
      designed to subgroup patients into a restrictive and a nonrestrictive group.
      RESULTS: Patients with restrictive filling pattern had a more severe left
      ventricular dysfunction and a higher cardiac mortality. Analysis by the Kaplan
      Meier method revealed that patients in the RFI > or = 1 and RFI < 1 groups had a
      cardiac events-free survival rate of 52% versus 94% at 1 year, and 27.5% versus
      92% at 2 years, respectively. The multivariate Cox proportional hazard model
      selected RFI as the most powerful prognostic factor (chi(2) = 8.8017, P = 0.0030)
      for all-cause cardiac death. CONCLUSION: These results indicate that RFI is a
      simple, noninvasive, and specific clinical predictor for adult chronic heart
      failure patients who are at a high risk for all-cause cardiac death.

PMID- 14975199
TI  - Clinical features and management of Crohn's disease in Chinese patients.
AB  - BACKGROUND: An increasing incidence of Crohn's disease has been found in China in
      recent years. Our study has been focused on evaluating the diversity of the
      clinical manifestations of Crohn's disease in order to improve early diagnostic
      accuracy and therapeutic efficacy. METHODS: Thirty patients with active Crohn's
      disease were enrolled and their clinical data, including diagnostic and
      therapeutic results, were analyzed. Endoscopy combined with histological
      examination of biopsy specimens provided characteristic features of the disease.
      Transabdominal bowel sonography (TABS) was used for detecting intestinal
      complications. Nutritional supportive therapy was given to 20 subjects with
      active cases of the disease. RESULTS: Most patients were young adults with a
      higher proportion of females to males (ratio: 1.14:1). The disease affects any
      segment or a combination of segments along with the alimentary tract (from the
      mouth to the anus). In this study, the colon and small bowel were the major sites
      involved. Recurrent episodes of abdominal pain in the right lower quadrant and
      watery diarrhea were the most common symptoms. Granulomas were identifiable in
      nearly one-third (30.8%) of all biopsy specimens. In moderate cases of the
      disease, remission was achieved more quickly through the use of oral prednisone
      therapy than with SASP or 5-ASA. Beneficial effects on the host's nutritional
      status were observed. Immunosuppressives were used on an individual basis and
      showed variable therapeutic effects. Sixteen patients had surgery due to
      intestinal obstruction or failure to respond to drug therapies. Rapid improvement
      after surgery was reported. CONCLUSION: Endoscopy (with biopsy) and TABS were
      both crucial procedures for diagnosis. SASP (or 5-ASA) and prednisone were
      effective as inductive therapies. Azathioprine has demonstrable benefits after
      induction therapy with prednisone. Surgery, as an alternative treatment, provided
      another effective choice in selected patients.

PMID- 14975200
TI  - Menopausal depression: comparison of hormone replacement therapy and hormone
      replacement therapy plus fluoxetine.
AB  - BACKGROUND: To compare the efficacy and safety of hormone replacement therapy
      (HRT) combined with fluoxetine, with HRT alone, in post-menopausal women
      suffering from depression. METHODS: A randomized, open-label, parallel trial was
      applied. HRT was administered to all patients for 2 cycles, with 14 days of
      estrogen therapy and 14 days of estrogen plus progesterone. Patients who were
      randomly assigned to the HRT plus fluoxetine group were given fluoxetine in
      combination with HRT. Hamilton Depression Rating Scale (HAMD), Kupperman
      Menopausal Index (KMI), and Clinical Global Impressions scale were used to
      measure the efficacy. RESULTS: One hundred and twenty-three post-menopausal
      patients with depression were enrolled in the study. Among them, 120 had at least
      one post-treatment visit and entered into the statistical analysis. The mean
      total HAMD scores were significantly lower, and the percentages of HAMD score
      reductions were higher in the HRT plus fluoxetine Group compared with the HRT
      Group, after at least 3 weeks of treatment, with an average difference of 5
      points at the endpoint. The Clinical Global Impression-Severity and Clinical
      Global Impression-Improvement scores were significantly different in the 2
      groups, in favor of the combination therapy. The mean total KMI was significantly
      lower in the Combination Group compared with the HRT Group, after at least 6
      weeks of treatment, with an average 4.5-point difference between the groups. No
      statistically significant differences were found in most of the adverse events
      reported in the Combination Group compared with the HRT group, with the exception
      of 3 symptoms, i.e., dry mouth, loss of appetite, and abdominal distention. They
      were mild to moderate in severity. Two patients in the HRT group, but none in the
      combination group, dropped out due to adverse events. CONCLUSION: HRT plus
      fluoxetine therapy was effective in the treatment of menopausal depression with a
      satisfactory safety profile.

PMID- 14975201
TI  - Small-diameter prosthetic H-graft portacaval shunts in the treatment of portal
      hypertension.
AB  - BACKGROUND: Portasystemic shunts, especially total shunts, are effective tools
      for reducing portal pressure and controlling variceal bleeding but lead to high
      risk of encephalopathy and accelerating liver failure. The purpose of this study
      is to evaluate the clinical effects of small-diameter expanded
      polytetrafluoroethylene (ePTFE) H-graft portacaval shunts in the treatment of
      portal hypertension. METHODS: Thirty-one patients with portal hypertension were
      treated with ePTFE small-diameter H-graft portacaval shunts from December 1995 to
      April 2002. Twenty-one had externally ringed grafts and 10 had non-ringed grafts;
      20 had 10 mm diameter grafts and 11 had 8 mm grafts. The left gastric artery and
      coronary vein were ligated in 22 patients. Additionally, 6 patients underwent
      pericardial devascularization, and splenectomies were performed on 30 patients.
      RESULTS: An average decrease of free portal pressure (FPP) from (32.13 +/- 4.86)
      cmH2O before shunting to (12.55 +/- 5.57) cmH2O after shunting was observed.
      Portal blood flow was reduced by 1/3 compared with the levels measured before
      shunting. Twenty-eight patients survived after the operation, and no upper
      gastrointestinal rebleeding occurred in the follow-up period (40.2 months on
      average). We lost contact with one patient. Color Doppler ultrasonography and/or
      portography revealed the shunts to be patent in 28 cases and occluded in 2 (6.4%)
      cases. Encephalopathy developed in 4 patients (12.9%). CONCLUSION: Small-diameter
      ePTFE H-graft portacaval shunts can effectively reduce portal pressure. Moreover,
      the majority of the hepatopetal flow from the portal vein can be adequately
      maintained. The reinforced shunts may achieve a higher rate of patency. Morbidity
      from encephalopathy was less frequent than in patients receiving total shunts.
      Small-diameter H-graft portacaval shunts are also effective in preventing
      recurrent variceal bleeding.

PMID- 14975202
TI  - Topical melagenine for repigmentation in twenty-two child patients with vitiligo
      on the scalp.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy of topical
      melagenine for repigmentation in child patients with vitiligo on the scalp.
      METHODS: Twenty-two child patients with vitiligo on the scalp were treated with
      1.2 mg/ml aqueous melagenine in combination with 20 minutes of infrared exposure
      twice daily. RESULTS: In 4 patients (18.2%), melagenine treatment in combination
      with infrared exposure led to complete recovery; in 6 patients (27.3%), treatment
      was shown to be effective; in 8 patients (36.3%), treatment led to improvements
      in patient condition; and only 4 patients (18.2%) showed no response after 1 - 2
      treatment sessions. The general effective rate of melagenine-infrared combination
      treatment was 45.5% for the children with vitiligo on the scalp, and treatment
      was accompanied by minimal side effects. CONCLUSION: Melagenine may be
      efficacious and a safe treatment option for childhood vitiligo affecting the
      scalp.

PMID- 14975203
TI  - Telomerase activity in cervical intraepithelial neoplasia.
AB  - BACKGROUND: It was reported that telomerase expression is closely associated with
      cellular immortality and cancer. This study was designed to investigate the
      relationship between telomerase expression and the carcinogenesis of cervical
      cancer, the possible use of telomerase as a marker of cervical intraepithelial
      neoplasia (CIN) progression or regression, and the natural history of CIN.
      METHODS: Telomeric repeat amplification protocol (TRAP) assay was used to measure
      telomerase activity in cervical scrapings and biopsy samples obtained from 105
      cases affected with various cervical conditions, including chronic cervicitis (n
      = 20), CIN (n = 64, 16 cases of CIN I, 20 cases of CIN II, and 28 cases of CIN
      III), and invasive squamous cell carcinoma (n = 21). RESULTS: In exfoliated cell
      samples, telomerase activity was detected in 5 of 20 (25.0%) cases of cervicitis,
      10 of 16 (62.5%) cases of CIN I, 11 of 20 (55.0%) cases of CIN II, 23 of 28
      (82.1%) cases of CIN III, and 13 of 21 (61.9%) cases of carcinoma. In cervical
      biopsy samples, telomerase activity was detected in 6 of 20 (30.0%) cases of
      cervicitis, 8 of 16 (50.0%) cases of CIN I, 9 of 20 (45.0%) cases of CIN II, 27
      of 28 (96.4%) cases of CIN III, and 20 of 21 (95.2%) cases of carcinoma.
      Telomerase activation was significantly higher in CIN samples than in cervicitis
      samples. Telomerase activity was detected at similar frequency in samples from
      cervical scrapings and cervical biopsies. CONCLUSION: These results seem to
      suggest that telomerase expression may be associated with carcinogenesis of the
      cervix. TRAP assay of cervical scraping samples could be used to monitor and
      predict the development of CIN in clinical practice.

PMID- 14975204
TI  - Differences in coronary microvascular lesions in coronary heart disease and
      hypertension: an autopsy study of elderly patients.
AB  - BACKGROUND: In the case of hypertension, lesions in the microvessels of the
      target organs precede and deteriorate further after arteriosclerosis in the small
      arteries. Thus coronary microvascular lesion (CML) was considered the crucial
      factor contributing to damage to the target organs. The purpose of this study is
      to observe the characteristics and differences of CML in autopsies of elderly
      patients with essential hypertension (EHT), coronary heart disease (CHD), or EHT
      with CHD, given the same degree of left ventricular wall thickness (LVWT).
      METHODS: A retrospective study was performed on 246 cases of patients over 60
      years old with EHT, CHD, or EHT with CHD, and on 26 cases without cardiovascular
      disease as controls, out of a total of 3195 consecutive autopsied cases. The
      arterioles (with diameter 10 - 60 microm) and the capillaries in the cardiac
      muscle layer were examined by haematoxylin and eosin staining, elastic van Gieson
      staining, and CD31 immunohistochemistry. To quantify CML severity, measurements
      were taken of arteriole density (AD), the ratio of wall-to-lumen area of
      arteriole (RWL), and capillary density (CD), using light microscopy and computer
      image analysis. Based on LVWT, the cases were divided into four degrees, from I
      to IV. The EHT, CHD, and EHT with CHD groups all rated LVWT I-IV, and the control
      group rated LVWT I. SAS software was used for statistical analysis. RESULTS: With
      the aggravation of LVWT, both AD and RWL increased while CD decreased
      significantly in the EHT group (P < 0.05 - 0.0001); there were similar but more
      severe changes in the EHT with CHD group (P < 0.001 - 0.0001); and AD increased
      (P < 0.001) while RWL and CD did not change significantly in the CHD group.
      CONCLUSION: Comparing EHT with CHD patients, there are similar patterns of change
      to AD, but different patterns of change to RWL and CD. CML is much more severe in
      EHT patients with CHD. We conclude that CML is one of the main causes of
      decreased coronary flow reserve and myocardial damage in both EHT patients and
      EHT patients with CHD.

PMID- 14975205
TI  - Differential thymosin beta 10 expression levels and actin filament organization
      in tumor cell lines with different metastatic potential.
AB  - BACKGROUND: To investigate the differential expression levels of thymosin beta 10
      (T beta 10) and the corresponding changes of actin filament organization in human
      tumor cell lines with different metastatic potential. METHODS: Four groups of
      nine human tumor cell lines with different metastatic potential were analyzed for
      the amount of T beta 10 mRNAs by Northern blot and for their peptide expression
      levels by immunohistochemistry. The filamentous actin (F-actin) was observed by
      staining of TRITC-phalloidin to detect changes in actin organization. RESULTS: In
      comparison with non-/weakly metastatic counterparts, T beta 10 was upregulated in
      highly metastatic human lung cancer, malignant melanoma and breast cancer cell
      lines. Staining of TRITC-phalloidin revealed less actin bundles, a fuzzy network
      of shorter filaments and some F-actin aggregates in the highly metastatic tumor
      cells. Meanwhile, the actin filaments were robust and orderly arranged in the non
      /weakly metastatic cancer cell lines. CONCLUSION: T beta 10 levels correlate
      positively with the metastatic capacity in human tumors currently examined. The
      increasing metastatic potential of tumor cells is accompanied by a loss of F
      actin, poorly arranged actin skeleton organizations and presence of F-actin
      aggregates. There is a consistent correlation between the elevated T beta 10
      expression and the disrupted actin skeleton.

PMID- 14975206
TI  - DNA sequences of Paragonimus skrjabini populations from five provinces in China.
AB  - BACKGROUND: To study differences among Paragonimus skrjabini (P. skrjabini)
      populations from five provinces in China (Guangdong, Fujian, Yunnan, Hubei, and
      Sichuan) and Paragonimus szechuanensis. METHODS: DNA sequences were obtained from
      the ITS2 and CO1 genes and phylogenetic trees were constructed from the results.
      Sequences were also obtained from several other species of Paragonimus for
      comparative purposes. RESULTS: Although differences existed in the DNA sequence
      among P. skrjabini populations from five provinces, the differences were very
      small. There was also some resemblance between P. miyazakii from Japan and Fujian
      strains of P. skrjabini. CONCLUSION: All studied populations can be regarded as
      different strains of P. skrjabini; P. szechuanensis is not a separate species but
      may be a geographical strain of P. skrjabini. We also found that P. miyazakii may
      be synonymous with P. skrjabini.

PMID- 14975207
TI  - NF-kappa B involved in transcription enhancement of TGF-beta 1 induced by Ox-LDL
      in rat mesangial cells.
AB  - BACKGROUND: To determine the binding activity of nuclear factor-kappa B (NF-kappa
      B) and the transcription of transforming growth factor-beta 1 (TGF-beta 1)
      induced by oxidized low density lipoprotein (Ox-LDL) in rat mesangial cells and
      to elucidate the mechanism of renal injury of Ox-LDL. METHODS: NF-kappa B binding
      activity was measured by gel shift assay in mesangial cells with or without
      inducement of Ox-LDL. Protein kinase inhibitors and activators were then used to
      determine the signal transduction pathways. In this course I kappa B protein
      expression was analyzed by Western blot assay. TGF-beta 1 mRNA was measured in
      mesangial cells exposed to Ox-LDL by RT-PCR assay. TGF-beta 1 promoter from -1551
      to +57 were constructed into a pGL3-Basic vector with a luciferase reporting
      gene. A putative binding site of NF-kappa B was mutated. The wild and mutant
      promoters activity was analyzed by transfection into mesangial cells. RESULTS: NF
      kappa B was activated by Ox-LDL persistently and rebounded in the early period.
      Ox-LDL induced NF-kappa B activation in a dose dependent way. It also induced I
      kappa B degradation in 2 hours and resumed to normal levels. NF-kappa B
      activation was not alleviated by inhibitors of protein kinase A (PKA),
      extracellular signal-regulated kinase (ERK), and p38 MAP kinase (p38MAPK).
      Inhibitors of protein kinase C (PKC) and proteinsome inhibited the enhancement of
      NF-kappa B binding activity. Ox-LDL induced the transcription of TGF-beta1 in a
      time and dose dependent manner. Mutation of the putative binding site of NF-kappa
      B reduced the activity of TGF-beta1 promoter. CONCLUSION: Ox-LDL induced
      activation of NF-kappa B persistently. It was probably regulated by the
      degradation of I kappa B mediated by PKC pathway. NF-kappa B may be involved in
      the enhancement of TGF-beta 1 induced by Ox-LDL in rat mesangial cells.

PMID- 14975208
TI  - Concentrations of propofol in cerebral spinal fluid: target-controlled infusion.
AB  - BACKGROUND: Although the performance of target-controlled infusion (TCI) have
      been studied extensively, the accuracy and safety of a TCI system that targets
      the effect site remains to be demonstrated. This study was to investigate the
      relations of TCI of propofol to its concentrations in cerebral spinal fluid
      (CSF), the effect-site concentrations and bispectral index (BIS). METHODS: Twelve
      mongrel dogs were used for investigations. The target effect-site concentration
      was set at 3 microg/ml and the infusion was lasted for 15 minutes. CSF and blood
      samples were then collected and propofol concentrations were determined by using
      high performance liquid chromatography with fluorescence detection. BIS and
      hemodynamic data were monitored continuously. RESULTS: The predicted plasma
      concentrations were generally overestimated. Median performance error (MDPE) and
      absolute median performance error (MDAPE) were -10.0% and 29.9% respectively.
      Propofol CSF concentrations were much lower than its effect-site concentrations.
      Changes in BIS were consistent with propofol concentrations in CSF, both of which
      changed direction at 5 minutes while the effect-site concentrations relatively
      lagged behind. Better correlation (r(2) = 0.9195) was found between BIS and CSF
      concentrations, when compared with that between BIS and effect-site
      concentrations (r(2) = 0.554). CONCLUSION: With 1% enflurane inhaled, the
      inconsistency of drug effect to the effect-site concentrations may result from
      inaccuracy of pharmacokinetic parameters. CSF may show effect-site concentrations
      more accurately than plasma when using target effect-site concentration infusion.

PMID- 14975209
TI  - Effect of human osteopontin on proliferation, transmigration and expression of
      MMP-2 and MMP-9 in osteosarcoma cells.
AB  - BACKGROUND: To explore the effect of human osteopontin (hOPN) on the
      proliferation, transmigration and expression of matrix metallproteinase-2 (MMP-2)
      and matrix metallproteinase-9 (MMP-9) in osteosarcoma (OS) cells in vitro.
      METHODS: The prokaryotic-expression vector of hOPN was produced. hOPN was then
      subcloned into E. coli BL21 (DE3) cells and purified with ProBond trade mark
      Columns. The proliferation, cell cycle and the expression of cyclin A in OS cells
      were investigated by using MTT assay, flow cytometry and Western blot
      respectively. The transmigration of OS cells was checked by using transwell cell
      culture chamber. The micro-pore-filter-membrane system was used to study the
      chemiotaxis of hOPN to OS cells. The levels of total protein were examined
      according to Coomassie Brilliant Blue manuals. The expression of MMP-2 and MMP-9
      were evaluated by detecting the volume of degradation of gelatin on SDS-PAGE gel.
      RESULTS: The prokaryotic-expression vector of hOPN and purified hOPN protein were
      achieved hOPN promoted OS cells proliferation in a dose-dependent manner, and
      stimulated cyclin A expression in OS cells to accelerate cell division cycle.
      hOPN facilitated the trans-membrane migration of OS cells. hOPN also enhanced the
      secretion of MMP-2 and MMP-9 in OS cells. CONCLUSION: hOPN could stimulate cyclin
      A expression in OS cells. hOPN has chemiotaxis to OS cells and increases their
      transmigration. hOPN enhances the secretion of MMP-2 and MMP-9 in OS cells.

PMID- 14975210
TI  - Specific inhibiting effects of Ilexonin A on von Willebrand factor-dependent
      platelet aggregation under high shear rate.
AB  - BACKGROUND: Ilexonin A (IA), purified from the Chinese herbal medicine
      Maodongqing (Ilex pubescens Hook, et Arn) has been commonly used in south China
      to treat thrombotic disorders. In this study, we aimed to study the inhibiting
      effects and mechanism of IA on von Willebrand factor (vWF)-dependent high shear
      induced platelet aggregation. METHODS: vWF-dependent high shear (10,800 s(-1))
      induced aggregation of platelets obtained from normal donors in the presence or
      absence of IA was measured by a modified cone-plate viscometer and shear-induced
      vWF binding was measured by quantitative flow cytometry with monoclonal antibody
      known to bind exclusively to the C-terminal domain of vWF (LJ-C3) directly
      labeled with fluorescein isothiocyanate (FITC). P-selectin surface expression was
      also measured by a similar method with FITC conjugated anti-P-selectin monoclonal
      antibody (WGA1). RESULTS: Shear-induced platelet aggregation was inhibited by IA
      in a dose-dependent manner. The extent of aggregation decreased from (78.6 +/-
      4.6)% in the absence of IA to (36.5 +/- 2.1)% in the presence of IA (3.3 mmol/L)
      (P < 0.0001, n = 9) with a high shear rate of 10800 s(-1). vWF binding and P
      selectin expression were also inhibited by IA in a dose dependent manner. The
      number of binding FITC-LJ-C3 molecules increased after exposure of platelet-rich
      plasma to a high shear rate of 10800 s(-1) for 6 minutes, but this shear-induced
      increased binding platelet surface vWF molecules and P-selectin expression can be
      decreased in the presence of IA. CONCLUSION: vWF binding and vWF mediated
      platelet activation, aggregation occurring under high shear rate were inhibited
      by IA. IA may be a unique antithrombotic drug inhibiting the vWF-GP Ibalpha
      interaction, and may thus facilitate drug design targeting arterial thrombosis.

PMID- 14975211
TI  - Diabetic retinopathy: VEGF, bFGF and retinal vascular pathology.
AB  - BACKGROUND: Previous research indicated that the development of diabetic
      retinopathy (DR) is closely related to the excessive expression of growth
      factors. This paper was to study the relationship of DR with vascular endothelial
      growth factor (VEGF), basic fibroblast growth factor (bFGF) and the retinal
      vascular pathological change. METHODS: Fifty-five Wistar rats, weighing 100 - 200
      g, were selected and randomly divided into four groups: control group (no
      streptozocin injection, n = 10), M1 group (streptozocin induced diabetes for 1
      month, n = 15), M3 group (streptozocin induced diabetes for 3 months, n = 15),
      and M5 group (streptozocin induced diabetes for 5 months, n = 15). In situ
      hybridization and immunohistochemistry were used to investigate the expressions
      of bFGF and VEGF on retinal vascular, and retinal vessels were observed by
      transmission electron microscope. RESULTS: There was no difference in the number
      of pericytes between M1 and control group (P > 0.05), but the number of pericytes
      decreased obviously in M3 and M5 groups compared with the control group (P <
      0.01, P < 0.001, respectively). Capillary embolization and non-cell capillary
      were seen in M5 group. Positive expression of VEGF was found in M5 group using in
      situ hybridization and immunohistochemistry respectively. Positive expression of
      bFGF could be seen in M3 (78%) and M5 group (89%). Most remarkable changes of
      vessels were observed in M5 group including fragmental thickness, split of
      basement membrane, swelling and distortion of endothelial cells. CONCLUSIONS: In
      retinal vascular of the streptozocin (STZ) rats, there shows the expression of
      bFGF at the third month and that of VEGF at the fifth month.

PMID- 14975212
TI  - Therapeutic effect of bFGF on retina ischemia-reperfusion injury.
AB  - BACKGROUND: Basic fibroblast growth factor (bFGF) plays important roles in retina
      degeneration, light injury, mechanical injury, especially in retina ischemia
      reperfusion injury (RIRI). This study was to investigate the therapeutical effect
      of bFGF on RIRI and its mechanisms. METHODS: Experimental RIRI was induced by
      increasing intraocular pressure (IOP) in the eyes of 48 rats. These rats were
      divided into normal control, ischemia-reperfusion and bFGF-treated groups.
      Histological and ultrastructural changes of in the retina of different groups
      were observed, and the number of retinal ganglion cells (RGCs) was quantitatively
      analyzed under microscopy. Apoptotic cells were detected using the TdT-dUTP
      terminal nick-end labeling (TUNEL) method. The expression of caspase-3 was
      determined by streptavidin peroxidase (SP) immunohistochemistry. Atomic
      absorption spectrum method was used to evaluate the intracellular calcium
      changes. RESULTS: At the early stage of retinal ischemia-reperfusion injury,
      retina edema in the treated group was significantly eliminated compared with the
      untreated ischemic animals. RGCs in the bFGF-treated group was more than those in
      the untreated ischemic group during the post-reperfusion stages. In ischemic
      group, apoptotic cells could be found at 6th hour after reperfusion and reached
      the peak at 24 hours. At 72nd hour no apoptotic cells could be found.The changes
      in caspase-3 expression had a similar manner. The intracellular calcium of rat
      retina began to increase at 1st hour, reached the peak at 24 hours, and began to
      decrease at 72 hours. The change of the three markers in the treatment group
      showed a similar pattern, but they were all relatively less obvious. CONCLUSION:
      Apoptosis may play a vital role in RIRI. bFGF may has therapeutical effects on
      RIRI by inhibiting the increase of intracellular calcium and caspase-3
      expression.

PMID- 14975213
TI  - In vivo distribution of c-myc antisense oligodeoxynucleotides local delivered by
      gelatin-coated platinum-iridium stents in rabbits and its effect on apoptosis.
AB  - BACKGROUND: Post-stenting restenosis is a significant clinical problem, involving
      vascular smooth muscle cells (VSMCs) proliferation and apoptosis. It is reported
      that c-myc antisense oligodeoxynucleotides (ASODNs) local delivered by catheter
      can inhibit VSMCs proliferation. This study was designed to assess tissue
      distribution of c-myc ASODN local delivered using gelatin-coated platinum-iridium
      (Pt-Ir) stents, and its effect on apoptosis of VSMCs. METHODS: Gelatin-coated Pt
      Ir stents that had absorbed caroboxyfluorescein-5-succimidyl ester (FAM) labeled
      c-myc ASODNs (550 microg per stent) were implanted into the right carotid
      arteries of 6 rabbits. Tissue samples were obtained at 45 minutes, 2 hours, and 6
      hours. Tissue distribution of c-myc ASODNs was assessed by fluorescence
      microscopy. In addition, 32 rabbits were randomly divided into two groups.
      Rabbits in the control group (n = 16) were implanted with gelatin-coated Pt-Ir
      stents, and those in the treatment group (n = 16) were implanted with gelatin
      coated stents that had absorbed c-myc ASODNs. 7, 14, 30, or 90 days (n = 4,
      respectively, for each group) after the stenting procedure, the stented segments
      were harvested, and histopathological examinations were performed to calculate
      neointimal area and mean neointimal thickness. The expression of c-myc was
      assessed using in situ hybridization (ISH) and immunohistochemical methods.
      Apoptotic VSMCs were detected using terminal deoxynucleotidyl transferase
      mediated dUTP nick end labeling (TUNEL) and transmission electron microscope
      (TEM). RESULTS: According to fluorescence microscopic results, FAM-labeled c-myc
      ASODNs were concentrated in the target vessel media at the 45 minutes time point,
      and then dispersed to the adventitia. Morphometric analysis showed that
      neointimal area and mean neointimal thickness increased continuously up to 90
      days after stent implantation, but that total neointimal area and mean neointimal
      thickness were less in the treatment group than in the control group at all time
      points (P < 0.0001). At day 7 and day 14 after stenting, there were no detectable
      apoptotic cells in either group. However, apoptotic cells were present in the
      neointima 30 and 90 days after stenting, and the number of apoptotic cells was
      less at 30 days than at 90 days. Meanwhile, c-myc ASODNs appeared to induce
      apoptosis in more cells in the treatment group than that in the control group.
      Typical apoptotic VSMCs were observable under TEM. The expression of c-myc was
      positive in the control group and negative or weakly positive in the c-myc ASODN
      treatment group, according to both ISH and immunohistochemical examination.
      CONCLUSION: Gelatin-coated Pt-Ir stent mediated local delivery of c-myc ASODNs is
      feasible. The localization of c-myc ASODN is primarily in the target vessel
      walls. c-myc ASODNs can inhibit VSMCs proliferation and induce its apoptosis
      after local delivery in vivo.

PMID- 14975214
TI  - Prophylactic treatment with growth hormone improves intestinal barrier function
      and alleviates bacterial translocation in stressed rats.
AB  - BACKGROUND: Damage to the gut barrier often occurs during critical illnesses. In
      such cases, it is very important to alleviate impairment of the intestinal
      barrier and protect intestinal barrier function. This study investigated the
      protective effect of growth hormone on intestinal barrier function in rats under
      stress. METHODS: This study consisted of prospective, randomized, and controlled
      animal experiments. Twenty-five Sprague-Dawley rats served as total parenteral
      nutrition (TPN) models and were divided into three groups: TPN group, sepsis
      (Sep) group, and growth hormone (GH) group. Another 8 rats served as normal
      controls. Each group received different stress stimuli. Rats were fed for 7 days,
      and samples were taken for examination 24 hours after gavaging with dual
      saccharides. RESULTS: The architecture of the small intestinal mucosa in the Sep
      group showed the most severe damage among all groups. Nitric oxide levels in
      blood plasma and immunoglobulin A levels in the intestinal mucosa of the GH group
      were significantly lower than in the Sep group (P < 0.02). There were no
      significant changes in CD3 counts and in the CD4/CD8 ratio between the four
      groups. Dual sugar tests and bacteriological examinations revealed that
      intestinal permeability and rate of bacterial translocation in the GH group were
      lower than in the Sep group (P < 0.01, respectively). CONCLUSION: Prophylactic
      treatment with growth hormone can alleviate damage to intestinal barrier function
      caused by trauma and endotoxemia in rats under stress.

PMID- 14975215
TI  - Evaluation of periodontal healing in class II furcation defects following guided
      tissue regeneration with two different types of polylactic acid membranes.
AB  - BACKGROUND: Guided tissue regeneration procedures provide predictable
      reconstruction of periodontal tissues in the treatment of furcation involvements
      in animals and humans. This study was to compare long-term effectiveness of two
      different types of polylactic acid (PLA) membranes on periodontal regeneration in
      surgically created class II furcation defects in dogs. METHODS: Full thickness
      mucoperiosteal flap was raised on the buccal aspects of the experimental teeth
      and class II furcation defects having 5 mm vertical dimensions were created on
      mandibular premolar III and IV on each quadrant. The exposed root surfaces were
      thoroughly planed and PLA membranes were placed over the experimental defects on
      both sites. One site received liquid polymer membrane (LPM), and resorbable
      periodontal mesh (RPM) membranes were applied to the other site. The animals were
      sacrificed at 7 months after surgery and the specimens were processed for
      histological evaluation. RESULTS: The average length of new attachment formed on
      the treated roots in both groups ranged from 3.02 mm to 4.5 mm. Complete bone
      filling was observed at the furcation sites. No statistically significant
      differences were found between two membranes in any of the parameters (P > 0.05).
      CONCLUSION: This study demonstrates favorable regenerative outcomes by the use of
      two different types of PLA membranes that could be used as alternatives for
      guided tissue regeneration (GTR).

PMID- 14975216
TI  - Protective effects of lidocaine injected into the hepatoduodenal ligament on warm
      ischemia-reperfusion injury to the rat liver.
AB  - BACKGROUND: Ischemia-reperfusion (IR) injury to the liver is still a critical and
      daunting problem in the field of hepatobiliary surgery. Ischemic preconditioning
      (IP) of the liver serves as an effective approach against IR injury. This study
      was to develop a novel procedure that could mimic IP, but might be more feasible
      than IP during surgery. METHODS: Eighty-two SD rats were randomly divided into 5
      groups. L group (n = 21): 0.4% lidocaine (10 mg/kg) was injected into the
      hepatoduodenal ligament 10 minutes before a 40-minute hepatic IR. IP group (n =
      16): a 5-minute ischemia was followed by a 10-minute reperfusion prior to a 40
      minute hepatic IR. ILR group (n = 15): after a 40-minute ischemia of the liver,
      0.4% lidocaine (10 mg/kg) was injected into the hepatoduodenal ligament 10
      minutes prior to a 40-minute reperfusion of the liver. IR group (n = 15): the
      liver of the rat was subjected to a 40-minute IR. Control group (n = 15): 0.9%
      sodium chloride was injected into the hepatoduodenal ligament without other
      treatments. The levels of plasma alanine transaminase (ALT) and aspartate
      transaminase (AST) were determined for each group after treatment. RESULTS: The
      mean concentrations of ALT and AST were (379.80 +/- 141.69) U/L and (606.05 +/-
      220.26) U/L for the L group, (334.64 +/- 141.94) U/L and (625.68 +/- 267.06) U/L
      for the IP group, (523.36 +/- 170.35) U/L and (765.47 +/- 238.45) U/L for the ILP
      group, (524.29 +/- 163.59) U/L and (764.63 +/- 246.79) U/L for the IR group, and
      (150.90 +/- 27.05) U/L and (298.15 +/- 47.68) U/L for the control group (standard
      error of the mean). CONCLUSION: A significant decrease in ALT and AST levels was
      observed in the L and IP groups when compared to the ILR and IR groups (P <
      0.05), but no significant difference in ALT and AST levels was observed in the L
      group when compared to the IP group (P > 0.05). These results suggest that
      pretreatment with lidocaine injected into the hepatoduodenal ligament prior to IR
      provides effective protection against subsequent IR injury to the liver. The
      novel approach of blocking innervation with lidocaine mimics hepatic IP, but is
      more convenient than IP at the time of liver surgery.

PMID- 14975217
TI  - The three-dimensional structure and the relationship between external and
      internal vascularizations in the brain of rat embryos.
AB  - BACKGROUND: There have been no detailed reports of the three-dimensional
      structure and the relationship between the external and internal vascularizations
      observed successively for a long duration in the rat fetus, although many authors
      have studied the vascular morphology of the developing brain. This study examined
      the three-dimensional structure of both the external and internal
      vascularizations of the prenatal rat telencephalon from embryonic days 12 (E12)
      to 20 (E20). METHOD: A microvascular casting method for scanning electron
      microscopy (SEM) was used in this study, along with vascular staining using gold
      gelatin solution-autometallography (GGS-AMG) after intravascular injection of
      colloidal gold, as well as hematoxylin-eosin (HE) staining for paraffin embedded
      specimens. RESULTS: In GGS-AMG stains, E16 fetuses had a few short perforating
      cortical blood vessels (SPCVs); E17 fetuses had long perforating cortico
      medullary vessels (LPCVs). Older fetuses had specific patterns of vascular
      networks in the cortex and the deeper subcortical part of the telencephalon. In
      the cortex, fine longitudinal blood vessels were connected by transverse
      channels. The deep telencephalon had fine blood vessels running in all
      directions. Using SEM, the external vascularization was already visible in E12
      fetuses as arborizations of arterial branches, forming a mesh of fine vascular
      networks covering the telencephalon. A coralliform fine venous plexus was
      observed in the external vascularization of E16 fetuses. There were ring-like
      anastomoses and bud-like protrusions in the network of small blood vessels, most
      likely the angiogenesis of fetal vessels. From E12 to E16, an immature and
      incomplete internal vascularization began to appear. There were short blood
      vessels with ballooned terminals branching from the external vascularization.
      They penetrated the brain tissue to form networks in the superficial layer,
      comparable to SPCVs. In E17 to E20 fetuses, tortuous venous branches, straight
      arterial blood vessels, and a fine network of small blood vessels formed the
      external vascularization. There were fewer arterial than venous branches
      connecting to the fine networks of small blood vessels. LPCVs were noted at E17,
      at the time the white matter emerged. They branched from the external
      vascularization, and perpendicularly penetrated the brain surface, traversing the
      cortical plate, and entering into the deep brain. At E17, arterial and venous
      blood vessels could be clearly distinguished in the external vascularization. At
      E20, the cortex and white matter contained specific arrangements of networks of
      fine blood vessels, as seen by GGS-AMG staining. CONCLUSION: These findings show
      that the development of both the external and internal vascularization follows
      the development of the telencephalon. In particular, the emergence of the
      cortical plate and white matter on E16 and E17 influence the development of both
      the internal and the external vascularization. The laminal arrangement of blood
      vessels was not observed corresponding to the respective laminal neuronal layers.

PMID- 14975218
TI  - Urine products of bone breakdown as markers of bone resorption and clinical
      usefulness of urinary hydroxyproline: an overview.
AB  - PURPOSE: The purpose of this study is to review the urine products of bone
      breakdown as markers of bone resorption and usefulness of urinary hydroxyproline.
      DATA: Related researches published in 1985 - 2000 were systematically reviewed.
      RESULTS: Bone markers could be used for early diagnosis of bone metabolic
      diseases. Biochemical markers of bone resorption that reflect osteoclast activity
      and/or collagen degradation provide a new and potentially important clinical tool
      for the assessment and monitoring of bone metabolism. Assessment of bone
      resorption can be achieved with measurement of urinary hydroxylysine glycosides,
      urinary excretion of the collagen pyridinium cross-links, urinary excretion of
      type I collagen telopeptide breakdown products (cross-linked telopeptides) and
      urinary hydroxyproline. CONCLUSION: Urinary hydroxyproline has been in use as a
      marker of bone resorption, but it lacks sensitivity and specificity. It is a
      modified amino acid that is a metabolic product of collagen breakdown.
      Hydroxyproline may be released either free or with fragments of the collagen
      molecule attached during bone resorption, and it is also liberated by the
      breakdown of complement and nonskeletal collagen.

PMID- 14975219
TI  - Transcoronary ablation of septal hypertrophy compared with surgery in the
      treatment of hypertrophic obstructive cardiomyopathy.

PMID- 14975220
TI  - Left atrial appendage flow velocity in rheumatic mitral stenosis.

PMID- 14975221
TI  - Relationship between hyperemesis gravidarum and Helicobacter pylori
      seropositivity.

PMID- 14975222
TI  - Effects of morphine and fentanyl on tumor necrosis factor-alpha and interleukin-6
      concentrations in human whole blood in vitro.

PMID- 14975223
TI  - Latex allergy in Bozyaka Social Security Hospital workers, Turkey.

PMID- 14975224
TI  - Mycobacterial spindle cell pseudotumor of lymph nodes after receiving Bacille
      Calmette-Guerin (BCG) vaccination.

PMID- 14975225
TI  - An unusual case of incidental rupture of liver hemangioma during labor.

PMID- 14975226
TI  - Three cases of hyperlipidemic pancreatitis in late pregnancy.

PMID- 14975227
TI  - Cesarean scar pregnancy: a case report.

PMID- 14975228
TI  - Circular versus longitudinal myometrial contractile response to selective
      tachykinin receptor agonists in rat.
AB  - This study compared the nature and magnitude of the contractile response produced
      in vitro by selective NK1, NK2 and NK3 tachykinin receptor agonists in circularly
      and longitudinally oriented strips of myometrium from ovariectomised and
      ovariectomised oestrogen-treated rats. The nature of the responses produced upon
      stimulation of the tachykinin receptors varied between the different myometrial
      preparations and the hormonal environment from which the tissue was taken.
      Variations included: (i) sustained contraction until washout of agonist; (ii)
      biphasic contraction until washout of agonist; and (iii) monophasic contraction.
      The major differences in magnitude of contractions were seen in preparations from
      oestrogen-treated animals in which responses to stimulation of all tachykinin
      receptors were reduced in comparison to preparations from non-oestrogen treated
      animals. Furthermore, the responses in circularly oriented myometrium
      preparations from oestrogen-treated animals were all markedly reduced compared to
      responses in longitudinally oriented myometrium preparations. These results
      suggest that the tachykinin receptors in longitudinally and circularly oriented
      myometrial layers are differentially regulated, especially in tissue isolated
      from an oestrogen-dominated environment.

PMID- 14975229
TI  - Use of a new drug delivery formulation of the gonadotrophin-releasing hormone
      analogue Deslorelin for reversible long-term contraception in male dogs.
AB  - In the present study, we tested the effect of treatment with a slow-release
      implant containing the gonadotrophin-releasing hormone agonist Deslorelin(TM)
      (Peptech Animal Health Australia, North Ryde, NSW, Australia) on pituitary and
      testicular function in mature male dogs. Four dogs were treated with Deslorelin
      (6-mg implant) and four were used as controls (blank implant). In control dogs,
      there were no significant changes over the 12 months of the study in plasma
      concentrations of luteinising hormone (LH) or testosterone, or in testicular
      volume, semen output or semen quality. In Deslorelin-treated dogs, plasma
      concentrations of LH and testosterone were undetectable after 21 and 27 days,
      testicular volume fell to 35% of pretreatment values after 14 weeks and no
      ejaculates could be obtained after 6 weeks. Concentrations returned to the
      detectable range for testosterone after 44 weeks and for LH after 51 weeks and
      both were within the normal range after 52 weeks. Semen characteristics had
      recovered completely by 60 weeks after implantation. At this time, the testes and
      prostate glands were similar histologically to those of control dogs. We conclude
      that a single slow-release implant containing 6 mg Deslorelin has potential as a
      long-term, reversible antifertility agent for male dogs.

PMID- 14975230
TI  - Male germ line stem cells: from cell biology to cell therapy.
AB  - Research using stem cells has several applications in basic biology and clinical
      medicine. Recent advances in the establishment of male germ line stem cells
      provided researchers with the ability to identify, isolate, maintain, expand and
      differentiate the spermatogonia, the primitive male germ cells, as cell lines
      under in vitro conditions. The ability to culture and manipulate stem cell lines
      from male germ cells has gradually facilitated research into spermatogenesis and
      male infertility, to an extent beyond that facilitated by the use of somatic stem
      cells. After the introduction of exogenous genes, the spermatogonial cells can be
      transplanted into the seminiferous tubules of recipients, where the transplanted
      cells can contribute to the offspring. The present review concentrates on the
      origin, life cycle and establishment of stem cell lines from male germ cells, as
      well as the current status of transplantation techniques and the application of
      spermatogonial stem cell lines.

PMID- 14975231
TI  - Effect of ovariectomy and graft position on cryopreserved common wombat (Vombatus
      ursinus) ovarian tissue following xenografting to nude mice.
AB  - Ovarian tissue xenografting may be applied to increase the population size of
      rare or endangered animals. However, optimal grafting conditions, such as graft
      position and recipient hormonal status, are yet to be established. The present
      study, using common wombat ovarian tissue, showed that development of xenografted
      ovarian tissue to the antral follicle stage can be achieved irrespective of graft
      position. However, increased graft recovery rates and follicle survival were
      evident after grafting under the kidney capsule compared with grafting to
      subcutaneous sites. No increase in follicle development was observed after
      placing grafts both under the kidney capsule and subcutaneously in the one
      recipient compared with grafts placed under the kidney capsule alone or
      subcutaneously alone. Removal of the recipient's own ovaries at the time of
      grafting accelerated graft follicle development, with antral follicles seen by
      Week 12 after grafting compared with by Week 16 in recipients that retained their
      own ovaries. More oocytes were collected from xenograft recipients receiving
      hormonal stimulation before collection compared with non-stimulated recipients.
      No oocytes were mature (extruded a polar body) at the time of collection or after
      a subsequent period of in vitro maturation. This is the first study to
      demonstrate that antral follicle development can occur and oocytes can be
      collected from xenografted common wombat ovarian tissue.

PMID- 14975232
TI  - Effect of different vitrification protocols for human ovarian tissue on reactive
      oxygen species and apoptosis.
AB  - The aim of the present study was to evaluate the effect of different
      vitrification protocols on reactive oxygen species (ROS) and apoptosis in human
      ovarian tissue. Human ovarian tissue pieces were exposed to different
      vitrification solutions. The intracellular redox state level was measured using
      the fluorescent dye dichlorodihydrofluorescein diacetate. Imaging of apoptotic
      cells was monitored by anti-caspase-3 immunolabelling after vitrification and
      warming. Following equilibration in either 40% ethylene glycol (EG) (v/v), 0.35 M
      sucrose + 10% egg yolk extract (v/v) or 40% EG (v/v), 18% Ficoll-70 (w/v) + 0.35
      M sucrose for 6 min, ovarian pieces were cooled to -196 degrees C using four
      different protocols. Tissue that was cooled very rapidly (plunged directly into
      liquid nitrogen in straws or on grids or plunged directly into metal filings
      precooled to -196 degrees C) showed no statistically significant increase in
      either tissue ROS levels or the number of apoptotic cells after warming. In
      contrast, cooling using a less rapid method (nitrogen vapour at -120 degrees C)
      resulted in significantly elevated ROS levels and apoptosis after warming. There
      were no significant differences between the two vitrification solutions. This
      indicates that human ovarian tissue pieces should be vitrified using very rapid
      cooling rates.

PMID- 14975233
TI  - In vitro and in vivo assessment of functional capacity of flow cytometrically
      sorted ram spermatozoa after freezing and thawing.
AB  - The effect of sex sorting and freeze-thawing on the viability and fertility of
      ram spermatozoa was investigated in the present study. Non-sorted (control)
      frozen-thawed spermatozoa had a higher motility and forwards progressive motility
      (FPM) than sorted frozen-thawed spermatozoa (60.9 +/- 2.9% v. 57.0 +/- 3.3% and
      4.0 +/- 0.1 v. 3.5 +/- 0.1 FPM, respectively; P < 0.001) after incubation (6 h at
      37 degrees C). Sorted and non-sorted (control) frozen-thawed spermatozoa had
      similar acrosome integrity (73.7 +/- 1.8% v. 75.2 +/- 2.1%, respectively) after
      thawing and incubation. A greater proportion of sorted spermatozoa displayed
      chlortetracycline staining patterns that were characteristic of capacitation
      (22.0 +/- 2.8%; P < 0.05) than non-sorted (control) spermatozoa (15.4 +/- 2.6% B
      pattern) before freezing. Overall, more sorted frozen-thawed spermatozoa showed
      patterns characteristic of being acrosome reacted (12.8 +/- 0.7%; P < 0.01) and
      less were uncapacitated (35.5 +/- 0.6%; P < 0.05) than non-sorted (control)
      frozen-thawed spermatozoa (7.7 +/- 0.8%; and 38.6 +/- 0.6% for AR and F pattern,
      respectively). Similar numbers of non-sorted (control) and sorted frozen-thawed
      spermatozoa migrated through artificial cervical mucus after 1 h (76.4 +/- 11.9
      v. 73.9 +/- 11.9 spermatozoa, respectively). The distance travelled by the
      vanguard spermatozoon was also similar (56.9 +/- 7.8 v. 38.6 +/- 5.8 mm for
      control and sorted spermatozoa, respectively). Sorted and control frozen-thawed
      spermatozoa displayed a similar pattern of binding to, and release from, an
      oviduct epithelial cell monolayer (OECM), but sorted frozen-thawed spermatozoa
      were released more rapidly (P < 0.05) than non-sorted (control) frozen-thawed
      spermatozoa. The pregnancy rate was higher for ewes inseminated with 100 x 10(6)
      (commercial control) frozen-thawed spermatozoa (59%) than for 5, 10, 20 and 40  x
      10(6) total sorted frozen-thawed spermatozoa (41% overall; P < 0.001).
      Insemination of 16 x 10(6) resulted in a higher pregnancy rate (31%) than 10(6)
      (17%; P < 0.05), but was similar to ewes that received 4  x 10(6) sorted frozen
      thawed spermatozoa (24%). Time of insemination (54, 58 and 62 h after sponge
      removal) had no effect on pregnancy rate. Pregnancy in gonadotrophin-releasing
      hormone-treated ewes was affected by insemination dose (P < 0.05) but not sperm
      type (sorted and non-sorted) or ram. Pregnancy was higher after insemination of
      40 x 10(6) than 5 or 20 x 10(6) non-sorted (control) or sorted frozen-thawed
      spermatozoa (70%, 33% and 35%, respectively; P < 0.05). Sorted frozen-thawed
      spermatozoa may have a shorter viability within the female tract than non-sorted
      frozen-thawed spermatozoa.

PMID- 14975234
TI  - Mast cells provide a "HINT" to the function of an exotic nucleotide.
AB  - One or more members of the HIT (histidine triad) family of proteins is encoded in
      the genomes of diverse species, ranging from prokaryotes to humans. However, the
      precise cellular and biochemical functions of many of these proteins are largely
      enigmatic. Therefore, the paper by Lee et al. in this issue of Immunity that
      ascribes a role for the histidine triad protein HINT (also designated HINT1) in
      regulating the activity of the microphthalmia transcription factor (MITF) is of
      great interest. Furthermore, this study implicates a role for an exotic
      endogenous nucleotide Ap4A in this process. This naturally occurring compound
      consists of two adenosines linked by four phosphate residues, and has been
      proposed as an intracellular and extracellular signaling molecule.

PMID- 14975235
TI  - Routes to transplant tolerance versus rejection; the role of cytokines.
AB  - The alloimmune response can be divided into specific junctures where critical
      decisions between tolerance and immunity are made which define the outcome of the
      transplant. At these "decision nodes" various cytokines direct alloresponsive T
      cells to develop either a proinflammatory response aimed at graft destruction or
      an immunoregulatory response facilitating graft acceptance. This review will
      focus on the role of these cytokines in influencing the progression of an
      alloimmune response leading ultimately to either allograft survival or rejection.

PMID- 14975236
TI  - T cell-independent somatic hypermutation in murine B cells with an immature
      phenotype.
AB  - Somatic hypermutation contributes to the generation of antibody diversity and is
      strongly associated with the maturation of antigen-specific immune responses. We
      asked whether somatic hypermutation also plays a role in the generation of the
      murine immunoglobulin repertoire during B cell development. To facilitate
      identification of somatic mutations, we examined mouse systems in which only
      antibodies expressing lambda1, lambda2, and lambdax light chains can be
      generated. Somatic mutations were found in cells, which, by surface markers, RAG
      expression, and rapid turnover, had the phenotype of immature B cells. In
      addition, expression of AID was detected in these cells. The mutations were
      limited to V regions and were localized in known hotspots. Mutation frequency was
      not diminished in the absence of T cells. Our results support the idea that
      somatic hypermutation can occur in murine immature B cells and may represent a
      mechanism for enlarging the V gene repertoire.

PMID- 14975237
TI  - The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF
      activity in FcepsilonRI-activated mast cells.
AB  - The involvement of microphthalmia transcription factor (MITF) in the function of
      mast cells, melanocytes, and osteoclasts has recently started to be investigated
      in depth. In a previous study, we found Hint to be associated with MITF in mast
      cells and showed that it suppresses MITF's transcriptional activity. Here, we
      have found that lysyl-tRNA synthetase (LysRS) is also associated with MITF and
      forms a multicomplex with MITF and Hint. We have also shown that Ap4A, an
      endogenous molecule consisting of two adenosine linked by four phosphate which is
      known to be synthesized by LysRS, is accumulated intracellularily above 700
      microM in IgE-Ag-activated mast cells, binds to Hint, liberates MITF, and thus
      leads to the activation of MITF-dependent gene expression. This implies that
      LysRS plays a key role via Ap4A as an important signaling molecule in MITF
      transcriptional activity.

PMID- 14975239
TI  - The collagen binding alpha1beta1 integrin VLA-1 regulates CD8 T cell-mediated
      immune protection against heterologous influenza infection.
AB  - A common feature of many infections is that many pathogen-specific memory T cells
      become established in diverse nonlymphoid tissues. A mechanism that promotes the
      retention and survival of the memory T cells in diverse tissues has not been
      described. Our studies show that the collagen binding alpha1beta1 integrin, VLA
      1, is expressed by the majority of influenza-specific CD8 T cells recovered from
      nonlymphoid tissues during both the acute and memory phases of the response.
      Antibody treatment or genetic deficiency of VLA-1 decreased virus-specific CTL in
      the lung and other nonlymphoid tissues, and increased them in the spleen. In
      spite of the increase in the spleen, secondary heterosubtypic immunity against
      flu was compromised. This suggests that VLA-1 is responsible for retaining
      protective memory CD8 T cells in the lung and other tissues via attachment to the
      extracellular matrix.

PMID- 14975238
TI  - SOCS3 is a critical physiological negative regulator of G-CSF signaling and
      emergency granulopoiesis.
AB  - To determine the importance of suppressor of cytokine signaling-3 (SOCS3) in the
      regulation of hematopoietic growth factor signaling generally, and of G-CSF
      induced cellular responses specifically, we created mice in which the Socs3 gene
      was deleted in all hematopoietic cells. Although normal until young adulthood,
      these mice then developed neutrophilia and a spectrum of inflammatory
      pathologies. When stimulated with G-CSF in vitro, SOCS3-deficient cells of the
      neutrophilic granulocyte lineage exhibited prolonged STAT3 activation and
      enhanced cellular responses to G-CSF, including an increase in cloning frequency,
      survival, and proliferative capacity. Consistent with the in vitro findings,
      mutant mice injected with G-CSF displayed enhanced neutrophilia, progenitor cell
      mobilization, and splenomegaly, but unexpectedly also developed inflammatory
      neutrophil infiltration into multiple tissues and consequent hind-leg paresis. We
      conclude that SOCS3 is a key negative regulator of G-CSF signaling in myeloid
      cells and that this is of particular significance during G-CSF-driven emergency
      granulopoiesis.

PMID- 14975240
TI  - C-terminal SRC kinase controls acute inflammation and granulocyte adhesion.
AB  - To establish whether the widely expressed regulator of Src family kinases Csk
      contributes to the control of acute inflammation in vivo, we inactivated csk in
      granulocytes by conditional mutagenesis (Cre/loxP). Mutant mice (Csk-GEcre)
      developed acute multifocal inflammation in skin and lung. Animals were protected
      from the disease in a microbiologically controlled environment, but remained
      hypersensitive to LPS-induced shock. Csk-deficient granulocytes showed enhanced
      spontaneous and ligand-induced degranulation with hyperinduction of integrins.
      This hyperresponsiveness was associated with hyperadhesion and impaired migratory
      responses in vitro. Hyperphosphorylation of key signaling proteins such as Syk
      and Paxillin in mutant granulocytes further supported breakdown of the activation
      threshold set by Csk. By enforcing the need for ligand engagement Csk thus
      prevents premature granulocyte recruitment while supporting the motility of
      stimulated cells through negative regulation of cell adhesion.

PMID- 14975241
TI  - Probabilistic regulation of IL-4 production in Th2 cells: accessibility at the
      Il4 locus.
AB  - IL-4 secreting and nonsecreting cells from Th2 cultures have a similar
      probability of producing IL-4 upon subsequent stimulation, implying that there is
      stochastic element in IL-4 production by stimulated Th2 cells. Purified IL-4
      producers and nonproducers have similar Gata3 and c-maf mRNA expression. Il4 gene
      accessibility, analyzed by restriction enzyme accessibility (REA) at sites in the
      promoter, in the second intron (DNase I hypersensitivity sites HSII and HSIII)
      and in CNS-1 in the two populations was also similar. However, upon TCR
      stimulation, site VA, which is 5 kB 3' of exon 4, displayed a striking increase
      in accessibility but REA was 2- to 3-fold greater in producers than nonproducers.
      Cyclosporin A treatment inhibited VA opening, implying the involvement of NFAT in
      increased VA accessibility. Induction of VA accessibility is sensitive to
      cycloheximide, suggesting an additional factor(s) is needed. Thus, opening of VA
      is a probabilistic event determining which Th2 cells transcribe Il4.

PMID- 14975242
TI  - Transcriptional inactivation of STAT3 by PPARgamma suppresses IL-6-responsive
      multiple myeloma cells.
AB  - Multiple myeloma (MM) remains largely incurable despite conventional and high
      dose therapies. Therefore, novel biologically based treatment approaches are
      urgently required. Here we demonstrate that expression of peroxisome proliferator
      activated receptor gamma (PPARgamma) in MM cells and its agonists 15-d-PGJ2 and
      troglitazone completely abolished IL-6-inducible MM cell proliferation and
      induced apoptosis through affecting expression of multiple cell cycle or
      apoptosis genes, whereas PPARgamma antagonist GW9662 and PPARalpha agonist
      WY14643 did not display this inhibitory effect. These PPARgamma agonists
      significantly inhibited DNA binding and transactivation of STAT3 bound to the
      promoter of target genes in chromatin, but did not affect the expression of IL-6
      receptor and phosphorylation of JAK/STAT3, MAPK, and PI3K/Akt. Interestingly,
      although inactivation of STAT3 by PPARgamma agonists is in a PPARgamma-dependent
      manner, the molecular mechanism by which two structurally distinct PPARgamma
      agonists suppress IL-6-activated STAT3 shows the divergent interactions between
      PPARgamma and STAT3 including direct or SMRT-mediated association.

PMID- 14975243
TI  - Human CD8+ T cells store RANTES in a unique secretory compartment and release it
      rapidly after TcR stimulation.
AB  - The chemokine RANTES is secreted rapidly after activation of human CD8+ T cells,
      with a cycloheximide-resistant burst during the first hour. This pattern was
      observed in purified memory and effector phenotype CD8+ cells from blood as well
      as in blasts. In contrast, secretion of other chemokines and interferon-gamma by
      these cells was sensitive to cycloheximide and detectable only after a lag.
      Immunofluorescence microscopy of CD8+ memory and effector cells and blasts showed
      RANTES present in intracellular vesicles that do not significantly colocalize
      with cytotoxic granule markers or other markers of defined cytoplasmic
      compartments. Immunoelectron microscopy confirmed that RANTES is stored in small
      vesicles distinct from the lysosomal secretory granules. RANTES+ vesicles
      polarize rapidly in response to TcR engagement and are more rapidly depleted from
      the cytoplasm. These results show that CD8+ T cells have two distinct TcR
      regulated secretory compartments characterized by different mobilization
      kinetics, effector molecules, and biological function.

PMID- 14975244
TI  - Developmentally distinct Th cells control plasma cell production in vivo.
AB  - Differential Ly6C expression identifies a major phenotypic division in
      CD44loCD62LhiCD4+ Th cells. Using two separate models of single subset adoptive
      transfer, we demonstrate the unique capacity of Ly6Chi Th cells to promote
      antigen-specific plasma cell production in vivo. In contrast, both compartments
      support germinal center formation and proliferate to equivalent levels upon TCR
      triggering in vivo and in vitro. Developmentally, CD4+CD8- thymocytes leave the
      thymus expressing low levels of Ly6C; 3 days later approximately 50% stably
      upregulate Ly6C without cell division or TCR engagement in the periphery.
      Interestingly, antigen-specific Th cell clonotypes unevenly assort into these
      peripheral compartments, creating separate TCR repertoires that underpin
      peripheral functional diversity. Taken together, these data reveal a
      developmentally distinct Ly6Chi naive Th cell compartment subspecialized to
      regulate plasma cell production in vivo.

PMID- 14975245
TI  - The Balbiani body and germ cell determinants: 150 years later.

PMID- 14975246
TI  - Fetal-maternal interactions: prenatal psychobiological precursors to adaptive
      infant development.

PMID- 14975247
TI  - Paradoxical role of methyl-CpG-binding protein 2 in Rett syndrome.

PMID- 14975248
TI  - Genetic approaches to analyzing mitochondrial outer membrane permeability.

PMID- 14975249
TI  - Mitochondrial dynamics in mammals.

PMID- 14975250
TI  - Histone modifications in corepressor functions.

PMID- 14975251
TI  - Death by Abl: a matter of location.

PMID- 14975254
TI  - Transcriptional regulation in neutrophils: teaching old cells new tricks.

PMID- 14975255
TI  - Tumor vaccines.

PMID- 14975256
TI  - Immunotherapy of allergic disease.

PMID- 14975257
TI  - Interactions of immunoglobulins outside the antigen-combining site.

PMID- 14975258
TI  - The role of antibodies in mouse models of rheumatoid arthritis, and relevance to
      human disease.

PMID- 14975259
TI  - MUC1 immunobiology: from discovery to clinical applications.

PMID- 14975260
TI  - Human models of inherited immunoglobulin class switch recombination and somatic
      hypermutation defects (hyper-IgM syndromes).

PMID- 14975261
TI  - The biological role of the C1 inhibitor in regulation of vascular permeability
      and modulation of inflammation.

PMID- 14975295
TI  - Fluorescence anisotropy assays for analysis of ISWI-DNA and ISWI-nucleosome
      interactions.

PMID- 14975296
TI  - Biophysical analysis of specific genomic loci assembled as chromatin in vivo.

PMID- 14975297
TI  - Visualization and 3D structure determination of defined sequence chromatin and
      chromatin remodeling complexes.

PMID- 14975298
TI  - Electron microscopic analysis of the RSC chromatin remodeling complex.

PMID- 14975299
TI  - Use of optical trapping techniques to study single-nucleosome dynamics.

PMID- 14975300
TI  - Single-molecule analysis of chromatin.

PMID- 14975301
TI  - Biochemical and structural characterization of recombinant histone
      acetyltransferase proteins.

PMID- 14975302
TI  - Use of nuclear magnetic resonance spectroscopy to study structure-function of
      bromodomains.

PMID- 14975303
TI  - Assays for the determination of structure and dynamics of the interaction of the
      chromodomain with histone peptides.

PMID- 14975304
TI  - Expression, purification, and biophysical studies of chromodomain proteins.

PMID- 14975305
TI  - Quantitative assays for characterization of the Sir2 family of NAD(+)-dependent
      deacetylases.

PMID- 14975306
TI  - Selective HAT inhibitors as mechanistic tools for protein acetylation.

PMID- 14975307
TI  - Histone deacetylase inhibitors: assays to assess effectiveness in vitro and in
      vivo.

PMID- 14975308
TI  - Immunochemical analysis of chromatin.

PMID- 14975309
TI  - Generation and characterization of antibodies directed against di-modified
      histones, and comments on antibody and epitope recognition.

PMID- 14975310
TI  - Generation and characterization of methyl-lysine histone antibodies.

PMID- 14975311
TI  - Tips in analyzing antibodies directed against specific histone tail
      modifications.

PMID- 14975312
TI  - Histone methylation: recognizing the methyl mark.

PMID- 14975313
TI  - Analysis of genome-wide histone acetylation state and enzyme binding using DNA
      microarrays.

PMID- 14975314
TI  - Use of chromatin immunoprecipitation assays in genome-wide location analysis of
      mammalian transcription factors.

PMID- 14975315
TI  - High-throughput screening of chromatin immunoprecipitates using CpG-island
      microarrays.

PMID- 14975316
TI  - Chromatin immunoprecipitation in the analysis of large chromatin domains across
      murine antigen receptor loci.

PMID- 14975317
TI  - The use of chromatin immunoprecipitation assays in genome-wide analyses of
      histone modifications.

PMID- 14975318
TI  - Sequential chromatin immunoprecipitation from animal tissues.

PMID- 14975319
TI  - Immunofluorescent staining of polytene chromosomes: exploiting genetic tools.

PMID- 14975320
TI  - Indirect immunofluorescent labeling of Drosophila polytene chromosomes:
      visualizing protein interactions with chromatin in vivo.

PMID- 14975321
TI  - X-chromosome inactivation in mouse embryonic stem cells: analysis of histone
      modifications and transcriptional activity using immunofluorescence and FISH.

PMID- 14975322
TI  - X inactivation in mouse ES cells: histone modifications and FISH.

PMID- 14975355
TI  - Expression of costimulatory molecules (CD80, CD86, CD28, CD152), accessory
      molecules (TCR alphabeta, TCR gammadelta) and T cell lineage molecules (CD4+,
      CD8+) in PBMC of leprosy patients using Mycobacterium leprae antigen (MLCWA) with
      murabutide and T cell peptide of Trat protein.
AB  - In leprosy, cell-mediated immunity (CMI) is more significant than humoral
      response to eliminate intracellular pathogen. T cell defect is a common feature
      in lepromatous leprosy (LL) patients as compared to tuberculoid type (TT)
      patients. For efficient initiation of CD4+, T cell response requires T cell
      receptor (TCR) activation and costimulation provided by molecules on antigen
      presenting cells (APC) and their counter receptors on T cells. In our previous
      study, the defective T cell function in LL patients was restored to a
      proliferating state with the release of TH1 type cytokines using mycobacterial
      antigen(s) with two immunomodulators (Murabutide (MDP-BE) and T cell epitope of
      Trat protein of Escherichia coli) by presenting the antigen in particulate form
      in vitro to PBMC derived from leprosy patients. This observation prompted us to
      study the expression of the costimulatory molecules (CD80, CD86, CD28, CD152),
      other accessory molecules (TCR alphabeta/gammadelta) and T cell lineage molecules
      (CD4+ and CD8+) during constitutive and activated state of peripheral blood
      mononuclear cells (PBMC) derived from normal and leprosy individuals using
      different formulations of Mycobacterium leprae total cell wall antigen (MLCWA),
      Trat and MDP-BE using flow cytometric analysis. An increased surface expression
      of CD80, CD86 and CD28 but decreased CD152 expression was observed when PBMC of
      normal, BT/TT (tuberculoid) and BL/LL (lepromatous) patients were stimulated in
      vitro with MLCWA+MDP-BE+Trat peptide using liposomal mode of antigen delivery,
      while opposite results were obtained with the antigen alone. Antibody inhibition
      study using antihuman CD80 or CD86 completely abolished the T cell
      lymphoproliferation, thereby reconfirming the importance of these costimulatory
      molecules during T cell activation/differentiation. Though the liposome-entrapped
      antigen formulation has no effect on expression of alphabeta/gammadelta T cell
      receptor, the constitutive levels of TCR gammadelta were high in lepromatous
      patients. Thus, TCR bearing gammadelta appears to have a negligible regulatory
      role in peripheral blood of leprosy patients. The percentage of cells positive
      for CD4+ are increased in inducible state in all the three groups, while CD8+
      positive cells were decreased in LL patients, thereby reconfirming the fact that
      priming of CD4+ cells are necessary for producing final effector functions.
      Lastly, intracellular cytokine staining experiment indicated that CD4+ cells are
      the major producers of IFN-gamma but not NK cells. The study highlights the
      reversal of T cell anergy especially in lepromatous patients through the
      modulation of costimulatory molecule expression under the influence of Th1
      cytokines, i.e., IL-2 and IFNgamma.

PMID- 14975356
TI  - Suramin has adjuvant properties and promotes expansion of antigen-specific Th1
      and Th2 cells in vivo.
AB  - Aluminum hydroxide and incomplete Freund's adjuvant (IFA) are the only adjuvants
      approved for human use. Both are T helper 2 (Th2) adjuvants, however, T helper 1
      (Th1) immunity is induced if microbial products such as mycobacteria, CpG's, or
      bacterial toxins are included in the adjuvant preparation. The usefulness of
      bacterial toxins, such as Pertussis toxin (PT) or Cholera toxin (CT), as
      adjuvants for human vaccination is limited by toxic side effects and high
      immunogenicity. Hence, we asked whether or not the adjuvant activity of bacterial
      toxins on Th1 and Th2 immunity could be mimicked by chemical compounds of small
      molecular weight and less immunogenicity. In the present study, we show that
      Suramin, a small molecular weight naphthylurea, which mainly acts on G-proteins
      and on P2X/P2Y receptors, promotes expansion of hen eggwhite lysozyme (HEL)
      specific Th1 and Th2 cells upon immunization of BALB/c mice with HEL in aluminum
      hydroxide (alum). The results indicated that the adjuvant effects of Suramin on T
      cell responses were mediated by enhancing the expression of MHC class II and
      costimulatory molecules on antigen presenting cells (APCs), and by increasing
      their pro-inflammatory cytokine production. Together, the results suggest that
      small molecular weight compounds such as Suramin could be used as alternative
      vaccine adjuvants.

PMID- 14975357
TI  - Environmental contaminant and disinfection by-product trichloroacetaldehyde
      stimulates T cells in vitro.
AB  - It had been shown previously that MRL+/+ mice exposed to occupationally relevant
      doses of the environmental contaminant trichloroethylene in their drinking water
      developed lupus-like symptoms and autoimmune hepatitis in association with
      activation of Interferon-gamma (IFN-gamma)-producing CD4+ T cells. Since
      trichloroethylene must be metabolized in order to promote the T-cell activation
      associated with autoimmunity, the present study was initiated to determine
      whether the immunoregulatory effects of trichloroethylene could be mimicked by
      one of its major metabolites, trichloroacetaldehyde (TCAA). At concentrations
      ranging from 0.04 to 1 mM TCAA co-stimulated proliferation of murine T-helper
      type 1 (Th1) cells treated with anti-CD3 antibody or antigen in vitro. TCAA at
      similar concentrations also induced phenotypic alterations commensurate with
      activation (upregulation of CD28 and downregulation of CD62L) in both cloned
      memory Th1 cells, as well as naive CD4+ T cells from MRL+/+ mice. TCAA-induced
      Th1 cell activation was accompanied by phoshorylation of activating transcription
      factor 2 (ATF-2) and c-Jun, two components of the activator protein-1 (AP-1)
      transcription factor. TCAA at higher concentrations was also shown to form a
      Schiff base on T cells, and inhibition of Schiff base formation suppressed the
      ability of TCAA to phosphorylate ATF-2. Taken together, these results suggest
      that TCAA promotes T-cell activation via stimulation of the mitogen-activated
      protein (MAP) kinase pathway in association with Schiff base formation on T-cell
      surface proteins. By demonstrating that TCAA can stimulate T-cell function
      directly, these results may explain how the environmental toxicant
      trichloroethylene promotes T-cell activation and related autoimmunity in vivo.

PMID- 14975359
TI  - Proinflammatory cytokines enhance COX-1 gene expression in cultured rat
      glomerular mesangial cells.
AB  - Glomerular mesangial cells (GMC) exert an essential maintaining effect on
      hemodynamic integrity and immune competence of the kidney through arachidonate
      metabolism. To clarify this, cultured rat GMC were measured for the expression
      and production of cyclooxygenase (COX) and excretion of prostaglandin (PG). The
      rat GMC spontaneously expressed type 1 cyclooxygenase (COX-1), but not COX-2. The
      PGE2 and thromboxane B2 (TXB2) were spontaneously produced by the cells.
      Interleukin (IL)-1beta (25 ng/ml), IL-8 (25 ng/ml), growth-related oncogene-alpha
      (GRO, 50 ng/ml) and tumor necrosis factor-alpha (TNF-alpha, 25 ng/ml) stimulated
      the COX-1 protein production as demonstrated by Western blot and enhanced PGE2
      synthesis in GMC, beginning on 2 h of incubation, and steadily enhanced TXB2
      synthesis over a 24-h period. Lipopolysaccharide (LPS, 100 ng/ml) enhanced both
      PGE2 and TXB2 syntheses from 2 h to at least 24 h of incubation. Collectively,
      the proinflammatory cytokines could enhance COX-1 but not COX-2 expression in GMC
      leading to increased PGE2 and TXB2 production. These biochemical events may be
      implicated in normal renal physiology as well as in pathogenesis of glomerular
      diseases.

PMID- 14975358
TI  - Maturation of monocyte-derived dendritic cells by Hochu-ekki-to, a traditional
      Japanese herbal medicine.
AB  - To investigate the immunological effect of the traditional Japanese herbal
      medicine (kampo), Hochu-ekki-to (HOT), on dendritic cells (DC), we examined in
      vitro if HOT would stimulate the maturation process of human monocyte-derived DC
      as do TNF-alpha and LPS. Monocytes from a healthy volunteer were cultured in the
      presence of IL-4 and GM-CSF, and the generated immature DC were stimulated with
      HOT, TNF-alpha, or LPS (HOT-DC, TNF-DC, and LPS-DC, respectively) for 2 days.
      Flow cytometric analysis showed that HOT stimulated DC to express the surface
      maturation markers CD80, CD83, and CD86 dose-dependently and that the up
      regulation level was identical to TNF-alpha and LPS. The antigen-uptake capacity
      of HOT-DC was determined by FITC-labeled albumin uptake. HOT-DC lost albumin
      uptake capacity comparable to LPS-DC, indicating DC maturity. IL-12 (p70)
      production by HOT-DC and TNF-DC was not increased in comparison with LPS-DC. The
      antigen-presenting capacity of HOT-DC as analyzed by allogeneic T cell
      proliferation was significantly increased in comparison with immature DC and was
      identical to LPS-DC. These results demonstrate that HOT stimulates DC maturation
      as well as the other known maturation factors, despite low IL-12 production, and
      suggests the possibility that DC maturation by HOT can play an important role in
      the improvement of the immunoregulatory function in patients with impaired host
      defense.

PMID- 14975360
TI  - Effect of a topical steroid on gene expressions for chemokines in mice with
      contact hypersensitivity.
AB  - Effects of a topical corticosteroid drug, diflucortolone valerate, on the mRNA
      expressions for four CC- and four CXC-chemokines, which have been reported to be
      associated with recruitment of different kinds of proinflammatory and
      inflammatory cells, were investigated by RT-PCR in mice with 2,4,6
      trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) response. All
      of the eight gene expressions were clearly up-regulated in the lesion site of the
      CHS response up to 24 h post-challenge of TNCB at which ear swelling response
      reached a peak, so that heavy infiltration of inflammatory cells consisting
      mainly of mononuclear cells and neutrophils was likely induced by these
      chemokines. Topical treatment with diflucortolone valerate suppressed completely
      the infiltrates as well as the ear swelling response. In addition, the up
      regulation of gene expressions for these eight chemokines were suppressed by the
      treatment, indicating that the corticosteroid drug attenuates the expression of
      chemokine genes essential for orientating nonspecific skin response to hapten
      specific CHS response through the recruitment of inflammatory cells from the
      circulation into the tissue site.

PMID- 14975361
TI  - Immunostimulating effects of sugar cane extract on X-ray radiation induced
      immunosuppression in the chicken.
AB  - The present study was undertaken to evaluate the effect of sugar cane (Saccharum
      officinarum L.) extract (SCE) on the immune system of X-ray immunosuppressed
      chickens. SCE (500 mg/kg/day) was administrated into the crop of 3-week-old
      chickens for three consecutive days before or after irradiation. The results
      indicated that administration of SCE before or after whole body X-ray irradiation
      enhanced both primary and secondary immune responses in chickens immunized with
      sheep red blood cells and Brucella abortus (BA) as well as cell-mediated immunity
      measured by delayed type hypersensitivity to human gamma-globulin.

PMID- 14975362
TI  - Signaling pathway involved in methionine enkephalin-promoted survival of
      lymphocytes infected by simian immunodeficiency virus in the early stage in
      vitro.
AB  - Methionine enkephalin, the endogenous opioid peptide, has a diversity of effects
      on the immune system. Although the biological effects of the pentapeptide have
      been well documented, little is known about the intracellular events involved in
      the effects of opioids on human immunodeficiency virus (HIV) infected immune
      cells. In the present investigation, the possible mechanism of apoptosis
      alleviated by exposure of methionine enkephalin at 1 micromol/l to CEM x 174
      cells, the hybrid lymphocytes, infected with simian immunodeficiency virus (SIV)
      in vitro is elucidated. Apoptosis and cell cycle analysis is carried out by flow
      cytometry, the phosphorylation of mitogen-activated protein kinases (MAPK) ERK1
      and ERK2 is detected by Western blotting assay, and changes of calcium
      concentration were analyzed using the calcium-sensitive dye Fluo-3 AM. The
      results exhibit that methionine enkephalin at the concentrations of 1 micromol/l
      increase remarkably the proportion of vital cells and decrease the apoptotic
      cells based on annexin V binding assay. In response to the treatment with
      methionine enkephalin, SIV-infected cells display a prolonged survival and are
      accumulated in G1 phase. Methionine enkephalin increase obviously the content of
      intracellular calcium in normal cells within 1-2 min and maintains a high level
      within monitoring time. However, the intracellular calcium reaches the highest
      level at 1 min and subsequently decline to background in SIV infected group. In
      addition, methionine enkephalin also elevates the levels of protein kinase C
      (PKC) activity and phosphorylated extracellular signal-regulated kinase (ERK)
      1/2. It is proposed that calcium-PKC-MAPK cascade is involved in methionine
      enkephalin-prolonged survival of SIV-infected cells in the early stages of virus
      infection. The results provide a further evidence for potential use of methionine
      enkephalin on the therapy of Acquired Immunodeficiency Syndrome (AIDS).

PMID- 14975363
TI  - Maitake beta-glucan MD-fraction enhances bone marrow colony formation and reduces
      doxorubicin toxicity in vitro.
AB  - Previous studies have indicated that MD-fraction (MDF), in which the active
      component is beta 1,6-glucan with beta 1,3-branches, has anti-tumor activity as
      an oral agent and acts as an immune adjuvant. Since some other beta glucans
      appear to promote mobilization of hematopoietic stem cells, the effects of a beta
      glucan extract from the Maitake mushroom "MD-fraction" on hematopoietic stem
      cells were examined in a colony forming assay. Here we report for the first time
      that MDF has a dose response effect on mouse bone marrow cells (BMC)
      hematopoiesis in vitro. Using the Colony Forming Unit (CFU) assay to detect
      formation of granulocyte-macrophage (CFU-GM) colonies, and the XTT cytotoxicitiy
      assay to measure BMC viability, the data showed that the addition of MDF
      significantly enhanced the development of CFU-GM in a dose range of 50-100
      microg/ml (p<0.004). The mechanism of action included significant increase of
      nonadherent BMC viability, which was observed at MDF doses of 12.5-100 microg/ml
      (p<0.005). In the presence of Doxorubicin (DOX), MDF promoted BMC viability and
      protected CFU-GM from DOX induced toxicity. In addition, MDF treatment promoted
      the recovery of CFU-GM colony formation after BMC were pretreated with DOX. These
      studies provided the first evidence that MDF acts directly in a dose dependent
      manner on hematopoietic BMC and enhances BMC growth and differentiation into
      colony forming cells.

PMID- 14975364
TI  - A chronic model for evaluating the itching associated with allergic
      conjunctivitis in rats.
AB  - The present study was performed to develop a new model for evaluating itching
      associated with allergic conjunctivitis in rats. Repeated topical application of
      antigen caused an increase in eye scratching behavior in sensitized animals, and
      a significant difference was observed from days 21 to 42. Almost the same
      findings were observed in allergic symptoms, hyperemia and edema. Instillation of
      histamine also resulted in an increase in eye scratching behavior. The
      sensitivity to histamine in eye scratching behavior was increased by topical
      antigen application for 42 days after sensitization. In addition, the number of
      conjunctival eosinophils was significantly increased by repeated topical antigen
      application from days 21 to 42 in sensitized rats. Some anti-allergic drugs such
      as olopatadine (H1 antagonist), cetiridine (H1 antagonist) and ramatroban
      (thromboxane A2 (TXA2) antagonist) caused an inhibition of eye scratching
      behavior induced by topical sensitization in a dose-related manner. However,
      zafirlukast (cys-LT antagonist) caused no significant inhibition even at a dose
      of 30 mg/kg. The findings in present model of itching in allergic conjunctivitis
      were mainly through histamine H1-activity, and thromboxane A2 receptors were also
      involved in the response.

PMID- 14975365
TI  - Promotion of Sophora subprosrate polysaccharide on nitric oxide and interleukin-2
      production in murine T lymphocytes: implicated Ca2+ and protein kinase C.
AB  - SSP1, a polysaccharide isolated from Sophora subprosrate, increased the
      productions of nitric oxide (NO) and interleukin-2 (IL-2) in murine splenic T
      lymphocytes. SSP1-treated T lymphocytes showed an enhanced activity of protein
      kinase C (PKC) from the cellular membrane fraction as well as an increase in
      concentration of cytoplasmic free Ca2+. The results showed that SSP1 activated T
      cells to release NO and secrete IL-2 by modulating activity of PKC and level of
      intracellular free calcium. Nifedipine, a Ca2+ blocker, inhibited the activation
      of T cells by SSP1, indicating a role of Ca2+ in the activation of T cells. SSP1
      treated T cells showed an enhanced translocation of PKC, indicating that SSP1
      activated T cells via the activation of PKC.

PMID- 14975366
TI  - Inhibitory effects of bucillamine on the expression of vascular cell adhesion
      molecule-1 in human umbilical vein endothelial cells.
AB  - Bucillamine (BUC) has been found to have beneficial effects in the treatment of
      rheumatoid arthritis (RA), in which the activation of endothelial cells plays an
      important role in the pathogenesis. The current studies examined the effect of
      BUC and its intramolecular disulfide form (BUC-ID) on the expression of adhesion
      molecules in human umbilical vein endothelial cells (HUVEC) stimulated with tumor
      necrosis factor-alpha (TNF-alpha). HUVEC (4 x 10(4)/well) were incubated with
      medium M199 containing heparin and 20% FCS with endothelial cell growth
      supplement (ECGS) for 24 h in the presence or absence of BUC or BUC-ID, after
      which the culture medium was replaced with ECGS free medium. Then the cultures
      were further carried out for additional 24 h with TNF-alpha (10 ng/ml) in the
      presence or absence of BUC or BUC-ID. BUC-ID, but not BUC, appeared to suppress
      the expression of VCAM-1 on HUVEC stimulated with TNF-alpha in a dose-response
      manner at its pharmacologically relevant concentrations (0.3-3.0 microg/ml),
      whereas only the 3 microg/ml concentration level of BUC-ID had a statistically
      significant effect, although the effect was relatively small. By contrast, lower
      concentrations of BUC-ID (1-3 microg/ml) suppressed the secretion of soluble VCAM
      1 by HUVEC much more effectively. Of note, at the concentration of 3 microg/ml
      neither BUC nor BUC-ID significantly influenced the expression of ICAM-1 and E
      selectin on TNF-alpha stimulated HUVEC. These results indicate that BUC-ID, but
      not BUC, specifically downregulates the surface expression of VCAM-1 as well as
      the release of soluble VCAM-1 by HUVEC stimulated with TNF-alpha. BUC-ID
      suppressed the production of solubleVCAM-1 by RA bone marrow CD34+ cells
      stimulated with SCF, GM-CSF and TNF-alpha more effectively than BUC. The data
      thus suggest that one of the mechanisms of action of BUC involves the inhibition
      of the activation of endothelial cells.

PMID- 14975367
TI  - Novel immunomodulatory oligonucleotides prevent development of allergic airway
      inflammation and airway hyperresponsiveness in asthma.
AB  - Oligodeoxynucleotides containing unmethylated CpG motifs (CpG oligos) have been
      shown to prevent development of allergic airway inflammation and airway
      hyperresponsiveness (AHR) in mouse models of asthma. Recently, we reported
      immunomodulatory oligonucleotides (IMOs) containing novel structures (immunomers)
      and synthetic immunostimulatory CpR (R=2'-deoxy-7-deazguanosine) motifs show
      potent stimulatory activity with distinct cytokine secretion profiles. Since type
      2 T cells predominate in asthma and increase in type 1 cells can prevent the
      differentiation of naive T lymphocytes to a type 2 phenotype, we hypothesized
      that IMOs can prevent the development of allergic airway inflammation and AHR in
      the ovalbumin (OVA)-sensitized and challenged mouse model. We found that co
      administration of novel IMOs during OVA-sensitization abrogated both early and
      late allergic responses (LARs). AHR to methacholine was also blocked with IMO
      treatment. Analysis of bronchoalveolar lavage (BAL) fluid of mice treated with
      IMOs demonstrated complete reduction in eosinophils, with concomitant decreases
      in both serum and BAL fluid IL-4, IL-5, and IL-6 levels. In addition, there was a
      significant reduction in serum IL-10 levels. IMOs, in general, significantly
      attenuated the rise in serum IgE levels. In comparison, IMOs showed a
      significantly more potent effect on early and late allergic response than a
      conventional CpG oligo in this model. These data suggest that the treatment with
      these novel IMOs prevents OVA-induced allergic airway inflammation and AHR in
      asthma in the mouse and may provide a useful agent in the treatment of human
      asthma.

PMID- 14975368
TI  - Expression of the negative co-stimulatory ligand sCD152 in the yeast, Pichia
      pastoris, and its regulation of antigen specific immune responses.
AB  - CD152, a ligand expressed on the surface of the activated T cells that inhibits
      co-stimulatory signals, is associated with negative regulation of T-cell
      activation in the antigen-presenting process. In order to interfere with immune
      signal transmission, obtain functional proteins with specific immunosuppressive
      effects, and regulate the immune response, we cloned the full-length
      extracellular domain of CD152 into the expression vector pPICTLA and transformed
      Pichia pastoris GS115 cells by electroporation. Yeast colonies expressing and
      secreting large quantities of the extracellular soluble fragment of CD152
      (sCD152) were isolated, and the protein was purified and used in assays designed
      to investigate the ability of sCD152 to regulate the immune system. In a series
      of antigen specific immune response interference tests in mice, human allogeneic
      mixed lymphocyte reaction and antigen specific lymphocyte transformation tests,
      we found that sCD152 had a marked immunosuppressive effect. This protein reduced
      antibody titer in mice immunized with BSA, significantly inhibited the killing of
      antibody-dependent cytotoxicity and CTL-mediated donor target cells, and reduced
      the expression of IL2 in mice. In the absence of exposure of sCD152, long-term
      stimulation (>5 days) by the same antigen in vivo partially restored the immune
      response-correlated stimulation index (SI), showing the characteristics of a
      primary immune response. Following the deletion of sCD152, however, there was no
      obvious inhibitory effect on the primary immune response triggered by the
      nonrelevant antigen OVA, indicating that sCD152 had an antigen-specific
      immunosuppressive effect and that the inhibitory effect of sCD152 required the co
      administration of antigen. These findings suggest that sCD152 may have clinical
      potential as an immunosuppressive agent.

PMID- 14975369
TI  - A human dual-color enzyme-linked immunospot assay for simultaneous detection of
      interleukin 2- and interleukin 4-secreting cells.
AB  - The enzyme-linked immunospot (ELISPOT) assay is an efficient technique for the
      enumeration of single cells secreting antibodies and cytokines. For simultaneous
      differentiation of individual cells producing interleukin-2 (IL-2) and
      interleukin-4 (IL-4) at a single cell level in human peripheral blood mononuclear
      cells (PBMCs), a human dual-color ELISPOT assay has been optimized. In the
      present system, the red spots corresponding to IL-2-secreting cells (T helper
      type 1, Th1, cells) were developed with horseradish peroxidase and the amino
      ethyl carbazole (AEC)/H2O2. The blue spots corresponding to IL-4-secreting cells
      (T helper type 2, Th2, cells) were developed with an alkaline phosphatase and the
      Vector blue. The usefulness of the assay method was tested. With this system, we
      could detect the IL-2- and IL-4-secreting cells simultaneously in human PBMCs of
      a juvenile rheumatoid arthritis (JRA) patient. This procedure provides useful
      information on clinical immune disorders.

PMID- 14975370
TI  - Matalliotakis IM, Goumenou AG, Koumantakis GE, Neonaki MA, Koumantakis EE,
      Dionyssopoulou E, Athanassakis I, Vassiliadis S. Serum concentrations of growth
      factors in women with and without endometriosis: the action of anti-endometriosis
      medicines [Int Immunopharmacol 2003; 3(1):81-89].

PMID- 14975372
TI  - Possible molecular mechanisms to account for the efficacy of allopurinol against
      experimental autoimmune uveitis.

PMID- 14975374
TI  - Opioids and renal function.
AB  - Opioids, both endogenous and exogenous, have a strong influence on the renal
      function through different mechanisms, producing changes in the renal excretion
      of water and sodium. Several studies have demonstrated that opioids influence
      renal function, according to the agonist profile used. Mu, kappa, and delta
      agonists produce different renal effects, although the mechanisms remain unclear.
      Experimental data have given the input for a possible therapeutic role of kappa
      agonists for some specific conditions, for example, in treating water retention
      or hyponatremia occurring in patients who have hepatic cirrhosis with ascites. On
      the other hand, changes in renal function might strongly condition the use of
      opioids in the clinical setting, and the knowledge of the relationship between
      opioids and renal function is mandatory for a tailored approach to accommodate
      the individual responses in terms of pain intensity, tolerance, and adverse
      effects experienced by these groups of patients. The influence of renal function
      when using different opioids in the clinical setting is reviewed, as well as
      problems related to transplantation, renal damage induced by opioid addiction,
      and problems related to the use of opioid antagonists in such conditions.
      PERSPECTIVE: Endogenous opioids exert physiologic effects on renal function, and
      the use of opioids may have an influence on renal activity. Renal impairment has
      a serious impact on the clearance of most opioids used in the clinical setting.
      Biochemical and clinical monitoring is mandatory to prevent serious
      complications.

PMID- 14975375
TI  - Study on biologic effects of radon and thermal therapy on osteoarthritis.
AB  - Radon therapy uses radon (222Rn) gas, which mainly emits alpha-rays and induces a
      small amount of active oxygen in the body. We first examined the temporal changes
      in antioxidants, immune, vasoactive, and pain-associated substances in human
      blood by therapy to elucidate the mechanism of osteoarthritis in which radon
      therapy is used as a treatment. Results showed that radon inhalation enhanced the
      antioxidation and immune function, and the findings suggest that radon therapy
      contributes to the prevention of osteoarthritis related to peroxidation reactions
      and immune depression. Moreover, the changes in vasoactive and pain-associated
      substances indicated increases in tissue perfusion brought about by radon
      therapy, suggesting that radon inhalation plays a role in alleviating pain.
      PERSPECTIVE: The findings suggest that an appropriate amount of active oxygen is
      produced in the body after radon inhalation, and this contributes to the
      alleviation of the symptoms of active oxygen diseases such as osteoarthritis.

PMID- 14975376
TI  - A new rodent model of hind limb penetrating wound injury characterized by
      continuous primary and secondary hyperalgesia.
AB  - This article reports the development of a new hind limb pain model in which an
      incisional stab wound is placed on the front and back of the calf, causing both
      superficial and deep tissue injury. The injury causes primary mechanical
      hyperalgesia on the calf and secondary hind paw hyperalgesia, which served as the
      focus of the present study. Animals with unilateral stab wounds showed a
      significant increase in percent paw withdrawal (secondary mechanical
      hyperalgesia, reversed by morphine administration) from 2 to 48 hours after
      surgery, but no evidence of thermal hyperalgesia. In contrast, animals with
      bilateral leg injuries showed bilateral secondary mechanical and thermal
      hyperalgesia. Rats with unilateral leg incisional stab wounds showed a
      significant decrease in cage activity in both the horizontal and vertical
      directions, monitored by using a novel activity box approach, as compared to
      their 24-hour baseline levels or to the activity of naive animals. Analysis of
      spinal cord Fos labeling demonstrated that calf injury significantly increased
      Fos expression in laminae I to VI of the L3-L5 cord segments. The data indicate
      that this model might be useful for evaluation of the mechanisms underlying
      penetrating injury-induced primary and secondary hyperalgesia or for testing the
      effect of analgesics on hyperalgesia induced by such injury. PERSPECTIVE: Stab
      wounds and other types of penetrating wounds routinely encountered in emergency
      rooms and clinics are accompanied by pain associated with superficial and deep
      tissue injury. Here we present a rodent stab wound model that affords an
      opportunity to study the mechanisms of pain associated with traumatic injury.

PMID- 14975377
TI  - A polymeric membrane dressing with antinociceptive properties: analysis with a
      rodent model of stab wound secondary hyperalgesia.
AB  - The putative antinociceptive properties of a commercially available polymeric
      membrane dressing were tested by using a hind limb penetrating stab wound model
      in which secondary hyperalgesia could be evaluated from the hind paw. We examined
      the responses to mechanical and thermal stimuli applied to the hind paw remote to
      2 small penetrating stab wounds of the calf. Application of the polymeric
      membrane dressing, but not gauze dressing, significantly reduced the development
      of both mechanical and thermal hyperalgesia induced by the penetrating stab
      wounds. In addition, animals with stab wounds showed a significant decrease in
      cage activity, and this decrease was prevented by application of the polymeric
      dressing. Analysis of spinal cord Fos expression demonstrated that the polymeric
      membrane, but not gauze, dressing significantly decreased stab wound-induced Fos
      expression in laminae I to VI of the ipsilateral L3-L5 cord segments. In
      addition, application of the polymeric membrane, but not gauze, dressing to the
      hind limb of naive animals elicited Fos expression in laminae III and IV of the
      lumbar spinal cord. The data indicate that this model might be useful for
      evaluation of the mechanisms underlying deep tissue injury-induced secondary
      hyperalgesia, but they also demonstrate that the polymeric membrane dressing
      tested is capable of significantly reducing secondary hyperalgesia. PERSPECTIVE:
      Surgery and other types of penetrating wounds cause pain that is not always
      relieved by opioids and/or less potent analgesics. The present results suggest
      that the polymeric membrane dressing tested here may be used alone or in
      conjunction with analgesics to relieve pain caused by penetrating tissue injury.

PMID- 14975378
TI  - Suramin inhibits spinal cord microglia activation and long-term hyperalgesia
      induced by formalin injection.
AB  - Previous studies in our laboratory have shown that long-term (a period of weeks)
      increases in pain-related behavior were correlated with the activation of spinal
      microglia after subcutaneous injection of formalin into the dorsal surface of 1
      hind paw. The present study examined whether intrathecal delivery of suramin (a
      P2 receptor antagonist) blocks microglia activation and long-term hyperalgesia
      induced by formalin injection. Suramin was administered by using an osmotic pump
      attached to an intrathecal catheter. Suramin delivery (1.25 microg/kg/h) began 1
      day before the formalin injection and lasted for 4 days. Rats were observed by
      using a modified hot plate test before and at different times after formalin
      injection. The spinal cord was surveyed for changes in microglia labeling as
      shown by OX-42 staining at different times after formalin injection. Suramin
      decreased both the hyperalgesic sensitivity to the thermal stimuli and microglial
      activation induced by formalin injection as compared to the saline-treated group.
      This suggests that adenosine triphosphate is one potential mediator that
      activates spinal cord microglia and enhances pain-related behavior in the
      formalin model. PERSPECTIVE: This report suggests that blocking specific spinal
      P2 receptors might decrease the central enhancement of pain caused by peripheral
      injury and inflammation. One mechanism might be by blocking the activation of
      spinal microglia. Thus, P2 antagonists might have therapeutic usefulness in
      certain pain conditions.

PMID- 14975379
TI  - Sialochemical and gustatory analysis in patients with oral sensory complaints.
AB  - Our objective was to perform concomitant taste and salivary analyses in subjects
      with oral sensory complaints (OSC), including burning mouth syndrome (BMS),
      idiopathic taste aberrations, and xerostomia without established etiology, to
      attempt to find a possible explanation for the mechanism underlying those
      complaints. BMS is a disorder characterized by a painful burning or scalding
      sensation in clinically normal and healthy oral mucosa. Taste and salivary
      analyses were performed on 163 subjects with OSC who complained of BMS, taste
      aberration, or xerostomia, alone or in combination. These subjects were compared
      with 84 healthy, age- and sex-matched control subjects. The salivary and taste
      analyses were found to be helpful in distinguishing control subjects from
      complaining subjects. The most striking result found was the great similarity of
      both salivary and taste analyses in the BMS, taste aberration, and xerostomia
      groups, which were significantly different from the results obtained in the
      control group. An oral neuropathy or neurologic transduction interruption induced
      by salivary compositional alterations is suggested as the possible etiology for
      the complaints. This report might add an important objective diagnostic tool to
      the clinician treating such patients. PERSPECTIVE: The merit of the current study
      stems from the fact that it suggests for the first time a salivary-related local
      neuropathic mechanism for oral sensorial complaints. This may be of paramount
      importance, both with respect to the biological background of these complaints
      and to the possible therapeutic modalities that might be offered to suffering
      patients.

PMID- 14975380
TI  - Intrathecal but not intravenous opioids release adenosine from the spinal cord.
AB  - Opioids increase spinal release of adenosine in rats, and analgesia from systemic
      and intrathecal morphine is reduced in animals by adenosine receptor antagonists.
      We performed 3 studies to determine whether opioid administration also induces
      adenosine release in humans. To determine the effect of intrathecal opioid
      exposure, 15 women received intrathecal fentanyl, 50 microg, or saline, and
      cerebrospinal fluid was sampled at 2-minute intervals for 6 minutes before
      surgery. In a second study, 8 healthy volunteers received intrathecal morphine,
      50 microg, plus fentanyl, 50 microg, with cerebrospinal fluid sampled 20 and 60
      minutes later. To determine the effect of intravenous opioid exposure, 9 healthy
      volunteers received intravenous remifentanil for 60 minutes, and cerebrospinal
      fluid was sampled before and at the end of the infusion. Adenosine concentrations
      were similar in the 3 studies before opioid administration. Intrathecal fentanyl
      or saline did not affect adenosine concentrations during the 6 minutes in the
      first study. Adenosine concentrations increased significantly 20 and 60 minutes
      after intrathecal morphine plus fentanyl was administered. In contrast, adenosine
      concentrations were unaffected by intravenous remifentanil. These results suggest
      that intrathecal but not systemic opioid analgesia in humans is associated with
      spinal release of adenosine. PERSPECTIVE: Although the role of adenosine release
      in the spinal cord for opioid receptor activation in subsequent analgesia from
      opioids is controversial in laboratory studies, these clinical data suggest that
      local opioid receptor stimulation in the spinal cord of humans does release
      adenosine. Whether adenosine participates in analgesia from spinal opioids in
      humans is not known, but spinal adenosine itself is analgesic in humans,
      consistent with an opioid-adenosine role in analgesia.

PMID- 14975382
TI  - Updating equine influenza strains in a combined equine influenza and herpesvirus
      vaccine.

PMID- 14975383
TI  - Laminitis in the 21st century--clinical awareness must include show horses.

PMID- 14975384
TI  - Science, epidemiological models and decision making.

PMID- 14975385
TI  - Classification of canine lymphoma: a step forward.

PMID- 14975386
TI  - Predictive models and FMD: the emperor's new clothes?

PMID- 14975387
TI  - Current research and theories on the pathogenesis of acute laminitis in the
      horse.
AB  - A large number of studies have been undertaken in recent years aimed at
      furthering our understanding of the complex mechanisms underlying the common and
      debilitating condition of acute laminitis in the horse. Many of these studies
      have either reinforced or cast doubt on previously held theories on the
      pathogenesis of this disease, while others have suggested new mechanisms which
      may play a key role in its development. This review seeks to put the current
      hypotheses into the context of this recent body of evidence. While a unifying
      theory may not yet seem to be achievable, this review demonstrates that most of
      the current theories are not mutually exclusive. Studies utilising in vitro and
      in vivo models of the disease, particularly addressing the areas of inflammation,
      haemodynamic disturbances and enzyme activation in the hoof, as well as the
      preceding events occurring in the hindgut, have helped to explain many clinical
      observations of the disease and may possibly lead to more effective therapies and
      means of prevention in the future.

PMID- 14975388
TI  - Modelling and costing BVD outbreaks in beef herds.
AB  - Results from an epidemiological model of an outbreak of Bovine Viral Diarrhoea
      (BVD) within a Scottish beef suckler herd are presented. These results concurred
      with field observations and encouraged us to fulfill the objective of providing
      an estimate of losses due to BVD to assist decision makers. Using the output from
      the model, estimates were made of losses associated with the outbreak. Without
      taking into account any financial premiums associated with disease-free status,
      the estimate of pound 37 (58) mean loss per cow per annum suggests that health
      schemes and vaccination should be of immediate financial interest to farmers and
      veterinary advisors.

PMID- 14975389
TI  - Efficacy and duration of immunity of a combined equine influenza and equine
      herpesvirus vaccine against challenge with an American-like equine influenza
      virus (A/equi-2/Kentucky/95).
AB  - It has been recommended that modern equine influenza vaccines should contain an
      A/equi-1 strain and A/equi-2 strains of the American and European-like subtype.
      We describe here the efficacy of a modern updated inactivated equine influenza
      herpesvirus combination vaccine against challenge with a recent American-like
      isolate of equine influenza (A/equine-2/Kentucky/95 (H3N8). The vaccine contains
      inactivated Influenza strains A-equine-1/Prague'56, A-equine-2/Newmarket-1/'93
      (American lineage) and A-equine-2/ Newmarket-2/93 (Eurasian lineage) and
      inactivated EHV-1 strain RacH and EHV-4 strain V2252. It is adjuvanted with
      alhydrogel and an immunostim. Horses were vaccinated at the start of the study
      and 4 weeks later. Four, six and eight weeks after the first vaccination high
      anti-influenza antibody titres were found in vaccinated horses, whereas at the
      start of the study all horses were seronegative. After the challenge, carried out
      at 8 weeks after the first vaccination, nasal swabs were taken, rectal
      temperatures were measured and clinical signs were monitored for 14 days. In
      contrast to unvaccinated control horses, vaccinated animals shed hardly any virus
      after challenge, and the appearance of clinical signs of influenza such as nasal
      discharge, coughing and fever were reduced in the vaccinated animals. Based on
      these observations, it was concluded that the vaccine protected against clinical
      signs of influenza and, more importantly, against virus excretion induced by an
      American-like challenge virus strain. In a second experiment the duration of the
      immunity induced by this vaccine was assessed serologically. Horses were
      vaccinated at the start of the study and 6 and 32 weeks later. Anti-influenza
      antibody titres were determined in bloodsamples taken at the first vaccination,
      and 2, 6, 8, 14, 19, 28, 32, 37, 41, 45 and 58 weeks after the first vaccination.
      Vaccinated horses had high anti-influenza antibody titres, above the level for
      clinical protection against influenza, against all strains present in the vaccine
      until 26 weeks after the third vaccination.

PMID- 14975390
TI  - Prognostic significance of morphological subtypes in canine malignant lymphomas
      during chemotherapy.
AB  - The aim of this study was to determine the response of different morphological
      subtypes of canine lymphoma to a standardized therapeutic protocol. Diagnosis of
      lymphoma was based on cytohistological analysis and immunophenotyping with
      antibodies against CD3 and CD79a of an enlarged lymph node or an extranodal mass.
      Fifty-seven cases were classified according to the updated Kiel classification
      adapted to the canine species, into 24 B-cell lymphomas (20 centroblastic
      polymorphic and four Burkitt-type subtypes), and 33 T-cell lymphomas (10
      pleomorphic mixed, 10 lymphoblastic, eight unclassifiable high grade
      plasmacytoid, and five small clear-cell subtypes). All dogs were clinically
      staged at diagnosis. The protocol used l-asparaginase, vincristine,
      cyclophosphamide, doxorubicin, and prednisone. First remission duration and
      overall survival time were evaluated. Although the T-cell phenotype was
      associated, on the whole, with a poor prognosis, as previously reported in
      veterinary and human medicine, the study showed significant prognostic
      differences between the B- and the T-cell subtypes of canine lymphoma and
      suggests that clinico-morphological characterization of the disease is justified
      in dogs, as in humans.

PMID- 14975391
TI  - A generic spreadsheet model of a disease epidemic with application to the first
      100 days of the 2001 outbreak of foot-and-mouth disease in the UK.
AB  - A generic, stochastic spreadsheet model was developed to calculate the number of
      cases within the first 100 days of a propagating epidemic and with the ability to
      incorporate generic control measures. Foot-and-mouth disease (FMD) epidemics were
      simulated with a range of assumptions about the number of cases incubating the
      disease on day 1 and the efficiency of control measures. Particularly severe
      epidemics resulted from scenarios with low efficiency of control measures and
      high numbers incubating. Control measures that prevented 0.8 of cases from
      resulting in new cases were able to reduce substantially the cumulative number of
      cases. The results of various scenarios using the model were compared to the
      number of cases of FMD in the first 100 days of the 2001 outbreak in the UK, with
      specific reference to cases in Cumbria and Anglesey. Potential practical and
      educational applications of the model are discussed.

PMID- 14975392
TI  - The similarity of the physical sign frequencies of bovine spongiform
      encephalopathy and selected differential diagnoses.
AB  - This paper describes a method which enables the similarity of diseases based upon
      their physical sign frequencies to be defined relative to bovine spongiform
      encephalopathy (BSE). The means of the absolute differences between the sign
      frequencies of BSE and the differential diagnoses were used as measure of
      similarity. Four sets of signs were compared. The most useful quantitative
      measurement of difference between the diseases was achieved when only the variant
      signs were used. Diseases that have a high similarity to BSE when the variant
      signs are compared are more likely to have case presentations that approximate to
      those found in BSE. These are the diseases that are most likely to be confused
      with BSE by clinicians. Previously published BSE differential diagnoses from
      clinical opinion and brain histopathology are reported and compared to the
      diseases used in this study.

PMID- 14975393
TI  - Parasitic helminths in the digestive tract of six species of owls (Strigiformes)
      in Spain.
AB  - A survey was carried out in Catalonia, Spain to determine the prevalence of
      parasitic helminths infesting the digestive tract of nocturnal raptors
      (Strigiformes). One hundred birds belonging to six owl species were examined. The
      number of birds examined ranged between three and 30. The overall level of
      infestation was 65% and the most frequent helminths present were nematodes,
      followed by trematodes, cestodes and acanthocephalans. Strigiformes showing the
      highest levels of infestation were little owls (Athene noctua), 86.7% of which
      were infested. Helminths with the highest prevalence were Synhimantus spp.,
      intestinal capillarids, Brachylaima spp., cestodes and Centrorhynchus aluconis.

PMID- 14975394
TI  - Experimental comparison of ketamine with a combination of ketamine, butorphanol
      and medetomidine for general anaesthesia of the Eurasian badger (Meles meles L.).
AB  - The refinement of anaesthetic regimes is central to improving the welfare of
      captured wildlife. The Eurasian badger (Meles meles) has been the subject of an
      intensive long-term ecological and epidemiological study at Woodchester Park,
      Gloucestershire, England. During routine trapping operations (June 21st, 2000
      January 23rd, 2001) an experimental trial was conducted on 89 badgers to compare
      the physiological effects of anaesthesia using ketamine hydrochloride alone, and
      in conjunction with medetomidine hydrochloride and butorphanol tartrate. The
      mixture induced a significantly longer period of anaesthesia, and either
      substantially reduced or eliminated the adverse effects associated with ketamine
      anaesthesia (e.g., excessive salivation, bouts of sneezing, rough recoveries, and
      muscle rigidity). In a sub-sample of badgers given the mixture, anaesthesia was
      reversed using atipamezole hydrochloride. Under ketamine anaesthesia, heart rates
      were initially significantly higher and respiration rates were consistently
      higher, than in badgers given the mixture. In all badgers heart rates declined
      and respiration rates increased during anaesthesia, but the rate of change was
      greatest in animals given only ketamine. Overall, the mixture provided a more
      balanced anaesthesia characterised by muscle relaxation and complete
      unconsciousness.

PMID- 14975395
TI  - Intratesticular morphometric, cellular and endocrine changes in dromedary bulls
      exhibiting azoospermia.
AB  - Twenty bulls, aged 7-12 years and selected from six dromedary farms were used in
      this study. Fifteen previously fertile animals were divided into fertile
      (controls) and infertile groups on the basis of abnormal scrotal contents
      following palpation and azoospermic ejaculates collected by electroejaculation.
      An examination of the clinical and histological findings as well as the
      testicular patterns of oestradiol-17beta, testosterone and histamine indicated
      that three bulls displayed normal ranges comparable to the controls but with
      bilateral spermatocoeles in the caput epididymides in conjunction with the soft
      texture of the testicles. Seven bulls showed moderate testicular firmness and
      springiness, a marked increase in testicular oestradiol-17beta and histamine
      concentrations, and increases in surface area, density of mast cells and
      percentages of seminiferous tubules containing premeiotic spermatogenic cells as
      well as decreases in testicular testosterone concentrations, surface area of
      Leydig cells and diameter of the seminiferous tubules. The remaining five
      infertile animals had small hard testicles, supranormal testicular testosterone
      concentrations, baseline values of testicular oestradiol-17beta and histamine,
      decreased numbers of Sertoli and mast cells, with a predominance (98.2%) of
      seminiferous tubules containing spermatogonia resting on a thickened tubular
      basement membrane. The results provide information on the relationship between
      gonadotrophin, testicular oestrogen, androgens and histamine as well as
      spermatogenesis in normal and azoospermic dromedary bulls.

PMID- 14975396
TI  - Intestinal candidiasis in a loggerhead sea turtle (Caretta caretta): an
      immunohistochemical study.
AB  - Post mortem examination of a juvenile loggerhead sea turtle (Caretta caretta)
      stranded in the Canary Islands revealed a fishing-line in the small intestine.
      Histologically, severe necrotic enteritis, multiple haemorrhages, and marked
      oedema of the intestinal submucosa were observed. Yeast cells and fungal hyphae
      were seen in the lamina propria of the intestinal mucosa and in the connective
      tissue of the submucosa. Because fungal cultures were not taken at the time of
      necropsy, an immunohistochemical study was performed in order to identify the
      fungus involved. Specific monoclonal and heterologously absorbed polyclonal
      antibodies served as the primary reagents for identification of aspergillosis,
      candidiasis, fusariosis, geotricosis, scedosporiosis, and zygomycosis, using an
      indirect immunofluorescence staining technique. The fungal elements were strongly
      stained only by a polyclonal antibody against Candida albicans and a monoclonal
      antibody against C. albicans. There are no known previous reports of Candida sp.
      causing skin disease or systemic mycotic infection in sea turtles.

PMID- 14975397
TI  - Immune responses to bovine respiratory syncytial virus (BRSV) following use of an
      inactivated BRSV-PI3-Mannheimia haemolytica vaccine and a modified live BRSV-BVDV
      vaccine.

PMID- 14975398
TI  - In vitro adherence and invasion of ovine mammary epithelium by Mannheimia
      (Pasteurella) haemolytica.

PMID- 14975399
TI  - An outbreak of pneumonic pasteurellosis in sheep due to Mannheimia (Pasteurella)
      haemolytica serotype 7.

PMID- 14975400
TI  - Ultrasound measurements of skin thickness after UV exposure: a feasibility study.
AB  - High-frequency ultrasound images were used to measure the thickness of the dermis
      and epidermis of four human subjects. These measurements were performed before
      and after a single exposure to ultraviolet radiation (UV). Doses ranging from 0.5
      to 3 minimal erythema doses (MED) were delivered to the skin of the back of four
      human subjects, and thickness measurements were made over a period of 16 days. We
      found: (1) exposures > or = 2 MED caused a 10-30% increase in the thickness of
      the dermis-epidermis layer; (2) the thickening response was not always in direct
      proportion to the UV dose; (3) maximum thickening response time was 48 h for the
      2.8-3.0 MED exposure levels; (4) "diffusion" or spreading of the thickening
      response to neighboring areas occurred in some cases, as far as 4 cm from the
      exposed region (center-to-center), with changes ranging from 12% to 17%; (5)
      decreased thickness of the dermis-epidermis layer of up to 12% was observed for 3
      out of 4 of the subjects.

PMID- 14975401
TI  - Activation of c-Jun N-terminal kinase is required for ultraviolet B-induced
      apoptosis of murine peritoneal macrophages in vitro.
AB  - The mechanisms of ultraviolet B (UVB)-induced apoptosis and the role of c-Jun N
      terminal kinase (JNK) mitogen activated protein kinase (MAPK) in murine
      peritoneal macrophages, the terminally differentiated non-dividing cells were
      investigated. Exposure of macrophages to UVB 100 mJ/cm2 induced rapid apoptosis
      concurrent with activation of JNK and mitochondrial cytochrome c release leading
      to procaspase-3 activation. Late into the UVB-induced apoptosis, a caspase
      mediated cleavage of Bid was observed. Caspase inhibitors N-Benzylocarbonyl-Val
      Asp-fluoromethyl ketone and N-Acetyl-Asp-Glu-Val-Asp-aldehyde inhibited the UVB
      induced apoptosis without preventing the release of cytochrome c and JNK
      activation. The inhibition of JNK MAPK prevented UVB-induced apoptosis,
      concomitant with inhibition in cytochrome c release and procaspase-3 activation.
      However, it had no effect on procaspase-8 activation. These results indicate that
      activation of JNK MAPK upstream of caspases might play an important role in the
      apoptotic process of macrophages exposed to UVB irradiation.

PMID- 14975402
TI  - Longer term assessment of photodynamic therapy for intimal hyperplasia: a pilot
      study.
AB  - PURPOSE: To determine the potential long term (three or six months) effectiveness
      of photodynamic therapy (PDT) in reducing intimal hyperplasia in swine. METHODS:
      Intimal hyperplasia in the abdominal aortae of swine was created by a combination
      of fat-supplemented diet and balloon catheter injury prior to PDT. Swine were
      randomly allocated into one of three groups which received either: (i) both drug
      and light (PDT), (ii) drug only, or (iii) light only. Twenty-four hours following
      administration of the photosensitizer PHOTOFRIN (porfimer sodium) at 2.5 mg/kg,
      two distinct 1 cm spots on the posterior wall of the abdominal aorta were
      illuminated by an argon pumped dye laser tuned to 630 nm for an energy fluence of
      120 J/cm2. After three or six months, swine were sacrificed, perfusion fixed, and
      had their aortae removed for light and electron microscopy. RESULTS: Intimal
      hyperplasia reduction following PDT persisted for the three or six months follow
      up period. Experimental vessels receiving PDT showed a 26.0+/-4.5% ( n = 2, ie.
      four spots) and 30.8+/-5.4% ( n = 1, ie. two spots) smaller percent intimal area
      after three or six months of recovery, respectively. Control groups receiving
      either light or drug only showed less than a 6% difference in percent intimal
      area. Medial and adventitial layers were unaffected in all groups. Electron
      microscopy demonstrated that the endothelium or endothelial-like cells had
      regenerated in both the posterior and adjacent areas of the abdominal aortae with
      no clear difference between them. CONCLUSIONS: These findings suggest that PDT
      may be beneficial in reducing intimal hyperplasia for up to three or six months
      in swine.

PMID- 14975403
TI  - Photoacclimation in spathiphyllum.
AB  - We studied photoacclimation in Spathiphyllum grown at an irradiance of 40 or 420
      micromol/m2 s (LL or HL, respectively). All parameters studied responded to
      acclimation. Leaves at LL, in contrast to HL, were thinner and oriented
      perpendicular to the incident light, had more chlorophyll per g f w, fewer
      stomata on the upper leaf surface and a reduced layer of mesophyll cells. Their
      chloroplasts at HL had wider grana with less thylakoids per granum, and better
      organized photosystems than at LL. PSI and PSII activities per mg chlorophyll (
      Vmax ), and PSI and PSII content (total activity per g f w), were lower at LL
      than at HL and so was the light requirement for saturation of the PSI or PSII
      partial photoreactions, suggesting that fewer photosystems with larger antenna
      size prevail at LL, but many more with smaller antenna size at HL. Analysis of
      chlorophyll distribution among the thylakoid pigment-protein complexes showed
      less antenna chlorophyll serving PSII (CPa+LHCP1+LHCP3) than that serving PSI
      (CPIa+CPI+LHCP2) at LL as compared to HL, and thus a lower PSII/PSI ratio at LL,
      in agreement with the general finding that LL plants, with larger PSII antenna
      size, have lower PSII/PSI ratio. The increase in PSI antenna size at LL was
      correlated with the increase in the distribution of chlorophyll in pigment
      protein complexes serving PSI, and a very large chlorophyll/protein molar ratio
      in the isolated CPI complex. On the other hand, the PSII antenna chlorophyll
      (CPa+LHCP1+LHCP3) on a g f w basis, and the chlorophyll a/b ratio remained more
      or less constant at LL or HL. This may reflect our finding that Spathiphyllum
      contains mainly the 27 kDa inner LHCII antenna protein, the size of which remains
      unaffected by photoacclimation. The increase in the distribution of chlorophyll
      in pigment-protein complexes serving PSII at HL, therefore, reflects the higher
      population of PSII at HL. Very high PSI activity was found at HL, which we
      attribute to the highly organized small in size PSI.

PMID- 14975404
TI  - Thylakoid dismantling of damaged unfunctional chloroplasts modulates the Cab and
      RbcS gene expression in wheat leaves.
AB  - Thylakoid membrane dismantling and Lhcb and RbcS nuclear gene expression have
      been analysed in leaves of wheat plants grown in high fluence rate light and
      deprived of photoprotective carotenoids by treatments with the two bleaching
      herbicides, either norflurazon or amitrole. The Lhcb transcript was not
      detectable in cells of norflurazon-supplied leaves, having chloroplasts totally
      devoid of both inner membranes and pigments. In contrast, a substantial amount of
      Lhcb mRNA could be found in cells of amitrole-treated leaves, whose severely
      damaged organelles still contained few strikingly altered and photosynthetically
      unfunctional thylakoids, as well as chlorophyll traces. A possible relationship
      between chlorophyll synthesis and Lhcb expression, with the transcript level
      depending on the rate of pigment production in photodamaged chloroplasts is
      discussed. Also the RbcS expression was linked to the chloroplast membrane
      photodamage. However, a detectable level of transcript was still produced in
      norflurazon-treated cells, despite complete thylakoid demolition. Thus, the wheat
      cell behaviour had to be placed between that of species, such as maize, in which
      the RbcS expression is broken off in these conditions, and that of species, such
      as pea, in which it is slightly lowered. Interestingly, the dramatically
      photodamaged chloroplasts still maintained the ability to synthesize proteins and
      this allowed SSU and LSU Rubisco subunits to be found in the organelles of both
      norflurazon- and amitrole-treated plants.

PMID- 14975405
TI  - Formamidopyrimidines as major products in the low- and high-intensity UV
      irradiation of guanine derivatives.
AB  - Two major UV-induced transformation products of guanosine (Guo) in oxygen-free
      aqueous solution were isolated and characterized using reverse-phase HPLC-ESI-MS
      and UV absorption spectrophotometric techniques. These products were identified
      as two different sugar isomers of 2,6-diamino-4-hydroxy-5-formamidopyrimidine
      ribonucleosides, FapyGuo. A formation quantum yield of the order of 10(-3) for
      these products was obtained at a 75 microM concentration of Guo, while an
      increase in the ground state concentration of Guo from 10(-5) to 10(-4) M
      decreased their formation yield by a factor of ten. The formation of FapydGuo was
      also observed in the 254 nm photolysis of 2'-deoxyguanosine. In addition, the
      formation FapyGua was identified in the UV photolysis of all the guanine
      derivatives investigated. A formation quantum yield of the order of 10(-4) was
      obtained for the latter product, except in the photolysis of Gua in which a
      higher formation yield (10(-3)) was determined. These results suggest that
      hydration of the radical cation of guanine, followed by opening of the imidazole
      ring to form Fapy products, is one of the main low-intensity UV radiation-induced
      photo-transformation pathway of the guanine derivatives in oxygen-free aqueous
      solutions. Furthermore, the formation of the Fapy products and base release
      occurs through a similar photo-transformation pathways using a high-intensity UV
      radiation source.

PMID- 14975406
TI  - The influence of water on the photochemical reaction cycle of proteorhodopsin at
      low and high pH.
AB  - Dried samples were prepared from suspension of proteorhodopsin. With HCl and NaOH
      the pH of the samples was adjusted below and above the pKa of the proton acceptor
      Asp-97, which was established earlier to be 7.1. Both types of samples were
      photoactive, and exhibited a truncated photocycle, compared to that measured in
      suspension. The photocycle of the low pH sample had a K like red shifted
      intermediate, decaying through an energized PR' intermediate to the ground state
      protein. The high pH sample had a more complex photocycle in which beside of the
      red shifted intermediate an M like intermediate could be identified, having a
      deprotonated Schiff-base. This blue shifted intermediate decays through an
      intermediate we designated PR', which is spectrally identical to the unphotolysed
      ground state. The humidity and temperature dependence of the photocycle in both
      cases was studied to understand the role of water in the function of the
      proteorhodopsin. The effects measured on proteorhodopsin were very similar to
      that measured earlier on bacteriorhodopsin.

PMID- 14975407
TI  - Pharmacokinetics of Photogem using fluorescence monitoring in Wistar rats.
AB  - In this study we investigated the pharmacokinetics of a hematoporphyrin
      derivative (Photogem) in Wistar rats using the fluorescence spectroscopy to
      evaluate the drug distribution in liver, kidney and skin tissues. The detection
      system is composed of a 532 nm exciting laser, a Y-type catheter for light
      delivery and collection, a monochromator and a computer for data acquisition. The
      analysis of the fluorescence spectra was based on the intensity of porphyrin
      emission bands from specific tissues of the investigated organ. A simple
      transport model is proposed to determine the accumulation and elimination times
      for each type of investigated tissue. The obtained results show the viability of
      the fluorescence spectroscopic technique for the drug concentration monitoring in
      different target tissues and related pharmacokinetics. These effects should be
      considered before any in vivo study of Photodynamic Therapy using Photogem.

PMID- 14975408
TI  - ADAM proteins in the brain.
AB  - ADAM proteins are a family of metalloproteinases with a disintegrin domain. They
      have proteolytic as well as adhesive functions and can be involved in cell fusion
      events. Some ADAM proteins are expressed in a highly tissue restricted fashion,
      whereas others are expressed quite ubiquitously. In the brain, ADAM proteins have
      a role in neural development, axon guidance and inflammatory responses. Although
      there may be some functional overlap, homozygous deletion of some ADAM genes in
      mice can have fatal consequences. The expression and possible role of ADAM
      proteins in the brain will be discussed.

PMID- 14975409
TI  - Snow sports related head and spinal injuries: an eight-year survey from the
      neurotrauma centre for the Snowy Mountains, Australia.
AB  - Neurotrauma from snow-sports related injuries is infrequently documented in the
      literature. In Australia no collective data has ever been published. The aim of
      this study is to document the injury pattern of snow sports related neurotrauma
      admissions to The Canberra Hospital, the regional trauma centre for the Snowy
      Mountains. A computerised hospital record search conducted between January 1994
      and July 2002 revealed 25 head and 66 spinal injury admissions. The incidence of
      severe injuries requiring referral to tertiary trauma hospital was estimated to
      be 7.4 per 100,000 skier-days and for head and spinal injury 1.8 per 1,000,000
      skier-days and 5.6 per 1,000,000 skier-days, respectively. Collision with a
      stationary object was disproportionately associated with head injury ( [Formula:
      see text] ) and falling forward with spinal injury ( [Formula: see text] ).
      Snowboarders tended to sustain cervical fractures more often than skiers (
      [Formula: see text] ). The importance of helmet usage in buffering the impact of
      head-on collision and the proposition of having both feet fastened to a snowboard
      in leading to cervical injury were highlighted.

PMID- 14975410
TI  - Increased risk of lead fracture and migration in dystonia compared with other
      movement disorders following deep brain stimulation.
AB  - Deep brain stimulation (DBS) therapy is a continually expanding field in the
      functional neurosurgical treatment of movement disorders. However, the occurrence
      of adverse events related to implanted hardware cannot be overlooked. We report
      on a specific feature noted in our experience of DBS-related complications. From
      1998 until present we have found an overall rate of 5.3% of DBS electrode lead
      dysfunction (out of 133 patients) in our series (slipped leads 2.3%, lead
      fracture 3.8%). Interestingly, all of these failures occurred in dystonia
      patients (18.4% of all dystonia patients and 9.2% of all electrodes). We
      postulate on mechanisms that may explain why these complications predominate in
      this group of patients.

PMID- 14975411
TI  - Spinal cord schistosomiasis: a prospective study of 63 cases emphasizing clinical
      and therapeutic aspects.
AB  - A prospective study was conducted on 63 patients with schistosomal
      myeloradiculopathy admitted to a university hospital in Brazil. They were
      evaluated according to a protocol and treated with corticosteroid and
      praziquantel. The disease, in general, presented as a lower cord syndrome of
      acute progression characterized by motor, sensory and autonomic dysfunctions. The
      severity of the clinical picture was different among the patients, but the
      symptoms were quite constant. Cerebrospinal fluid examination showed an
      inflammatory pattern with or without eosinophils and/or IgG against schistosomal
      antigens. The most frequent alterations detected by imaging methods were
      enlargement of the medullary cone and of the roots of the cauda equina.
      Schistosome egg counts suggested a low parasite burden in 71.6% of the cases.
      Outcome was favorable in 38 (60.3%) patients and improvement usually started
      within the first 48 h after commencing on corticoid and was faster during the
      early period of treatment.

PMID- 14975412
TI  - Intracranial aneurysms in Sarawak General Hospital over a 30-month period.
AB  - This is a prospective study conducted from February 2000 to July 2002 in a single
      neurosurgeon neurosurgical service in the state of Sarawak, Malaysia. There were
      66 cases of subarachnoid hemorrhage or intracranial aneurysm presenting to this
      hospital over the study period. Fifty cases had their aneurysms clipped. Eighty
      percent of our patients were operated within 48 h of presentation. Forty-four
      percent presented with poor WFNS grades of 4 and 5. We had a 20% operative
      mortality and 29% total management mortality. Twenty-nine (58%) of the operated
      cases had a favorable outcome with a mean follow-up of 32 weeks. Multiple
      aneurysms were less common. The diagnosis of aneuysmal subarachnoid hemorrhage
      and clipping of aneurysms have increased dramatically over the previous two and
      half years indicating an increased awareness of the diagnosis and treatment. This
      series supports the previously reported beliefs that the lower rate of aneurymal
      subarachnoid hemorrhage in developing countries is likely due to both
      underdiagnosis and undertreatment. Good results can be achieved in developing
      countries with early diagnosis and intensive management.

PMID- 14975413
TI  - Intracerebral haemorrhage: surgical therapy vs. patient-adapted treatment
      concept.
AB  - In spontaneous intracerebral haemorrhage (SICH), the indication for surgery is
      still controversial. Therefore we developed clinical guidelines for therapy and
      compared the outcome of these patients to an exclusively surgically treated
      group. We retrospectively evaluated outcome in 70 patients with SICH, who were
      treated only surgically and compared this group with 58 prospectively collected
      patients, who were treated surgically (n=13) or medically (n=45). Initial level
      of consciousness, haematoma volume, and ventricular extension of blood were
      inversely correlated with mortality (p<0.0001, respectively). Use of clinical
      guidelines reduced the number of operations without affecting the outcome. We can
      formulate the following guidelines according to our data: comatose patients with
      and without brain herniation signs should be treated conservatively. Patients
      with a haematoma volume between 25 and 85 ml and a clinical deterioration are
      candidates for surgical therapy.

PMID- 14975414
TI  - Stereotactic biopsy for multifocal, diffuse, and deep-seated brain tumors using
      Leksell's system.
AB  - Using the Leksell stereotactic system, we selectively performed 91 biopsies for
      surgically inaccessible brain lesions. There were 25 multiple (27.5%), 15 diffuse
      (16.5%), and 51 (56.0%) deep-seated lesions. However, we avoided subjecting the
      patients with lesions adjacent to major vascular trunks or complex vascular
      structures such as the cavernous sinus, peri-insular regions and the pineal
      regions to stereotactic biopsy. The diagnosis was histologically confirmed in 84
      cases (92.3%). Sixty-nine (75.8%) lesions were primary tumors; 44 (48.4%) were
      malignant gliomas, 18 (19.8%) malignant lymphomas, and five (5.5%) low-grade
      gliomas. Thirteen (14.3%) cases had previously undergone radiation and/or
      chemotherapy for brain tumors, seven had recurrent glioma (five with malignant
      transformation) and six manifested radiation necrosis. None of the patients died
      due to the stereotactic procedure; one (1.1%) exhibited morbidity due to
      complicated hemorrhage. We found asymptomatic minor bleeding occurred in nine
      (9.9%) patients; the rate of hemorrhage was significantly higher in patients with
      preoperative angiographic evidence of tumor stain. Two patients (2.2%) suffered
      seizures, in one case seizure was induced by electric stimulation test at the
      target site. All five patients younger than 15 years underwent the procedure
      without complications. The Leksell stereotactic system is useful for diagnostic
      tissue sampling and contributes effectively to the selection of appropriate
      therapy in patients with malignant brain tumors. While it carries a low morbidity
      rate without mortality in our series, care must be taken for selected target
      sites in highly vascularized lesions exhibiting positive tumor stains.

PMID- 14975415
TI  - Atypical presentations of conus medullaris and filum terminale myxopapillary
      ependymomas.
AB  - Out of 27 cases of spinal ependymomas seen during a 21 year period (1978-1999),
      we observed three out of 12 myxopapillary tumours of the conus medullaris and
      filum terminale with atypical presentations. All the three cases presented with
      subarachnoid haemorrhage and intracranial hypertension. In addition, the second
      patient developed persistently low CSF sugar, while the third patient developed
      hydrocephalus, acute autonomic crisis and SIADH. Although subarachnoid
      haemorrhage (SAH), intracranial hypertension and hydrocephalus were previously
      scarcely reported in the literature, the low CSF sugar, acute autonomic crisis
      and SIADH were never reported singly or in combination. Up to our best knowledge,
      this is the first report that clearly outlines all these atypical manifestations
      in this particularly interesting neoplasm. Hence, the above challenging clinical
      presentations should be borne in mind with cryptic presentations of lower spinal
      cord and filum terminale ependymomas. A proposal of the mechanism of their
      production is suggested.

PMID- 14975416
TI  - Surgical experience of syringomyelia with reference to the findings of magnetic
      resonance imaging.
AB  - We present our surgical experience of 20 patients with syringomyelia, who were
      divided into two groups based on the findings of magnetic resonance (MR) imaging:
      a "non-visible cisterna magna" group, in which MR imaging did not reveal
      cerebrospinal fluid (CSF) in the cisterna magna, and a "visible cisterna magna"
      group. Patients with non-visible cisterna magna were associated with Chiari
      malformation (14 patients) or tight cisterna magna (4 patients) and underwent
      craniocervical decompression. Intradural exploration was performed when CSF
      movement in the cisterna magna or CSF outflow from the fourth ventricle appeared
      to be insufficient. It is important to confirm CSF outflow from the foramen of
      Magendie. Patients with visible cisterna magna were associated with tuberculous
      meningitis (2 patients) and underwent shunting procedures. Postoperatively,
      improvement in symptoms and a reduction in syrinx size were demonstrated in all
      patients except one. Two patients experienced recurrence of symptoms and syrinx
      dilatation.

PMID- 14975417
TI  - Anaesthesia for paediatric epilepsy surgery.

PMID- 14975418
TI  - Surgical anatomy of the anterior clinoid process.
AB  - We studied the surgical anatomy of the anterior clinoid process (ACP) and its
      adjacent structures in cadaver heads. We paid special attention to the anatomical
      relationships between the ACP and adjacent structures to determine the surgical
      landmarks for safe anterior clinoidectomy. Thirty-five cadaver heads were
      dissected and the ACP regions were examined in 55 skull sides. We observed that
      in eight sides the ACP had been pneumatized from the sphenoid sinus. The
      caroticoclinoid foramen was revealed in only eight sides. The extra-ocular nerves
      ran forward to the superior orbital fissure at the inferolateral aspect of the
      ACP, with the oculomotor nerve being closest. The posterolateral area of the
      carotico-oculomotor membrane was thin and incomplete in nine sides. The study
      clarified the anatomical relationship between the ACP and its surrounding
      structures, and identified the major variations experienced. We used these to
      identify anatomical landmarks to assist the surgeon in the planning of a safe and
      effective anterior clinoidectomy.

PMID- 14975419
TI  - Images in neuroscience: question. Erdheim-Chester disease.

PMID- 14975422
TI  - Head holder for microsurgical dissection.
AB  - A new apparatus to hold cadaveric head is described. The apparatus has a ring
      with the possibility of attaching multiple screws. The assembly is attached to a
      heavy rectangular base. The apparatus provides wide manoeuverability and firm
      stabilisation of the head in the desired optimal surgical position.

PMID- 14975420
TI  - Plasticity of gene expression in injured human dorsal root ganglia revealed by
      GeneChip oligonucleotide microarrays.
AB  - Root avulsion from the spinal cord occurs in brachial plexus lesions. It is the
      practice to repair such injuries by transferring an intact neighbouring nerve to
      the distal stump of the damaged nerve; avulsed dorsal root ganglia (DRG) are
      removed to enable nerve transfer. Such avulsed adult human cervical DRG (
      [Formula: see text] ) obtained at surgery were compared to controls, for the
      first time, using GeneChip oligonucleotide arrays. We report 91 genes whose
      expression levels are clearly altered by the injury. This first study provides a
      global assessment of the molecular events or "gene switches" as a consequence of
      DRG injuries, as the tissues represent a wide range of surgical delay, from 1 to
      100 days. A number of these genes are novel with respect to sensory ganglia,
      while others are known to be involved in neurotransmission, trophism, cytokine
      functions, signal transduction, myelination, transcription regulation, and
      apoptosis. Cluster analysis showed that genes involved in the same functional
      groups are largely positioned close to each other. This study represents an
      important step in identifying new genes and molecular mechanisms in human DRG,
      with potential therapeutic relevance for nerve repair and relief of chronic
      neuropathic pain.

PMID- 14975423
TI  - Epidural hematoma of the cervical spine after cervical laminectomy in a patient
      with ventriculo-peritoneal shunt.
AB  - Cervical laminectomy is one of the most common procedures performed in the
      sitting position. However in the presence of intracranial hypotension, a negative
      intradural pressure develops when the patients are in the sitting position. They
      are therefore at risk of developing cervical spinal epidural hematomas after
      cervical laminectomy. We report a case of a shunted patient who developed an
      epidural hematoma 3 days after a cervical laminectomy procedure in a seated
      position when he began to ambulate. When performing a cervical laminectomy
      procedure on a shunted patient, an upright position should be avoided during the
      operation. Intra-operative hypercapnia as well as intra- and post-operative
      intravenous hydration should be maintained in order to increase intradural
      pressure, preventing the formation of cervical spinal epidural hematoma after
      cervical laminectomy.

PMID- 14975424
TI  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) in a Chinese family: clinical, radiological and
      skin biopsy features.
AB  - We describe the clinical, radiological, genetic and skin biopsy findings of the
      first Chinese family with cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL). Of the 43-member family
      tree extending over three generations, eight had typical clinical features of
      CADASIL with recurrent ischemic stroke. In the three surviving affected family
      members, brain MRI showed extensive leukoaraiosis. Genotyping revealed
      heterozygous C to T mutation at nucleotide 406 in exon 3. Unusual clinical
      features were cerebellar infarction as a presenting complaint and a late age of
      onset with mild symptoms at age 69. A novel finding is the suggestion of a direct
      correlation between clinical disease severity and the quantity of ultrastructural
      pathognomonic granular osmophilic material (GOM) seen on skin biopsy.

PMID- 14975425
TI  - Recurrent Miller-Fisher syndrome.
AB  - A case of recurrent Miller-Fisher syndrome is presented and features of this very
      rare condition are discussed.

PMID- 14975426
TI  - Melkerrson-Rosenthal syndrome with cardiac involvement.
AB  - Melkerrson-Rosenthal syndrome (MRS) is a granulomatous disease usually restricted
      to the orofacial region. We report a case of MRS in a 37-year-old Malay patient
      who presented with complete heart block on a background of recurrent oro-facial
      swelling and facial diplegia. Lip biopsy showed lymphohistocytic granulomatous
      inflammation typical for MRS. Extensive work-up excluded other causes of the
      complete heart block. To our knowledge, this is the first reported case of MRS
      affecting cardiac connective tissues and the first report of MRS in an ethnic
      Malay. We postulate granulomatous infiltration of the conductive tissues as the
      basis for the heart block. Another unusual feature of the case was the presence
      of left eye abduction limitation.

PMID- 14975427
TI  - Traumatic acute subdural hygroma mimicking acute subdural hematoma.
AB  - Subdural hygroma is a frequent delayed complication of head trauma. Most hygromas
      are clinically 'silent' and a few cases have shown slow deterioration in the
      chronic stage. We report a case of subdural hygroma showing unique radiological
      findings and rapid deterioration. A 74-years-old female presented with a mild
      headache and consciousness disturbance after head injury. Computed tomography
      showed a midline shift as a result of two components piling up in the subdural
      space; the outer components showed low density, the inner components high
      density. Magnetic resonance imaging demonstrated that these two subdural
      components were subdural hygroma and subarachnoid hematoma. Simple burr hole
      irrigation, rather than large craniotomy, was thought to be more appropriate
      treatment to reduce the mass effect. Simple burr hole irrigation was performed to
      remove the subdural hygroma and the patient showed an excellent recovery. Careful
      examination of the radiological findings prevented an unnecessary procedure in
      this case. A possible mechanism of this phenomenon is discussed.

PMID- 14975428
TI  - Normal pressure hydrocephalus manifesting as transient prosopagnosia,
      topographical disorientation, and visual objective agnosia.
AB  - Usually, dementia, gait disturbance and urinary incontinence are an integral part
      of the clinical presentation of normal pressure hydrocephalus (NPH). However, NPH
      with transient visual cognitive disorders has not been reported previously. We
      herein describe an extremely rare case of NPH that presented with transient
      visual cognitive disorders and long lasting visual memory disturbances that
      subsided after CSF shunting. A 38-years-old man developed transient
      prosopagnosia, topographical disorientation, color vision disturbance, and visual
      objective agnosia that progressed over 5 years. Magnetic resonance images showed
      ventriculomegaly with ischemic lesions in the paraventricular deep white matter.
      ECD-SPECT showed a reduction of the cerebral blood flow (CBF) in the
      periventricular deep white matter. Three months after CSF shunting, the
      radiological findings normalized with dramatic improvement of the extremely rare
      symptoms.

PMID- 14975429
TI  - Arachnoid cyst presenting as subdural hygroma.
AB  - Arachnoid cysts are developmental lesions which are usually asymptomatic or may
      present with a variety of clinical features. Subdural hygroma is an extremely
      unusual complication associated with arachnoid cysts. A case of subdural hygroma
      that developed after the rupture of an asymptomatic middle cranial fossa cyst,
      following minor head injury is reported.

PMID- 14975430
TI  - Hypokalemic paralysis revealing Sjogren's syndrome.
AB  - A rare case of a lady with acute hypokalemic quadriparesis and underlying distal
      renal tubular acidosis manifesting as a presentation of Sjogren's syndrome is
      described. The case highlights the concept that acute hypokalemia due to
      unrecognized renal tubular acidosis may unmask Sjogren's syndrome in patients
      without sicca symptoms and it may be a marker of more severe renal disease. Acute
      paralysis is a life threatening consequence of hypokalemia and when due to
      potassium wasting secondary to renal tubular acidosis may be easily prevented.
      Underlying Sjogren's syndrome should be considered in all patients of either sex
      and at any age presenting with hypokalemic paralysis.

PMID- 14975431
TI  - Re-occlusion of the superior sagittal sinus after surgical recanalisation.
AB  - A 24-year-old woman was struck on the head by a hammer. Because of early signs
      and symptoms of intercranial hypertension, she underwent surgery for elevation of
      the depressed fragments which was compressing the superior sagittal sinus (SSS).
      After operation, the intracranial pressure (ICP) once decreased, but it gradually
      increased again. After hypothermia and barbiturate therapy, she recovered fully
      except for partial visual field defect due to brain contusion. A carotid
      angiogram 28 days after injury revealed complete occlusion of the whole SSS with
      good collateral circulation. After brain edema had subsided, a follow-up
      angiogram revealed normal blood flow through the SSS. Elevation of depressed bony
      fragments is required for a case presenting with early signs and symptoms of
      intracranial hypertension due to sinus compression. In a case with severe
      destruction of the SSS, one needs to know that re-occlusion of the dural sinus
      may occur after surgical recanalisation.

PMID- 14975432
TI  - A giant fusiform basilar aneurysm treated by bilateral vertebral artery
      occlusion.
AB  - OBJECTIVE AND IMPORTANCE: Fusiform aneurysms of the vertebrobasilar arteries that
      progressively enlarge causing symptomatic brainstem compression are dangerous and
      their treatment is difficult. A patient with such an aneurysm treated
      successfully with staged, microsurgical occlusions of the proximal vertebral
      arteries is described, and the literature pertaining to this rare condition is
      briefly reviewed. CLINICAL PRESENTATION: A 48-year-old man with a fusiform
      basilar trunk aneurysm of uncertain etiology presented initially with transient
      ischemic attacks (TIAs) of the posterior circulation that ceased with
      anticoagulation. Four years later he presented again with progressive ataxia,
      dysphagia and dysphonia due to considerable enlargement of the aneurysm causing
      brainstem compression. INTERVENTION: Staged microsurgical vertebral artery
      occlusions proximal to the aneurysm were performed. The second (left) vertebral
      artery was clipped only after the patient passed its temporary occlusion with an
      endovascular test balloon. The aneurysm subsequently thrombosed, the distal
      basilar artery kept patent by a single (left) posterior communicating artery. The
      patient's clinical condition improved markedly over a number of months as the
      aneurysm mass atrophied. CONCLUSION: Giant vertebrobasilar aneurysms are rare but
      treacherous lesions, sometimes justifying aggressive management. Carefully
      selected patients with progressive and severe symptoms due to brainstem
      compression may tolerate proximal vertebral artery occlusions, provided there is
      adequate collateral flow to the basilar termination and all of its perforating
      branches.

PMID- 14975433
TI  - Primary central nervous lymphoma presenting as bilateral cerebellopontine angle
      lesions: a rare case report.
AB  - The authors describe a rare case of primary central nervous system (CNS) lymphoma
      presenting as bilateral cerebellopontine angle lesions. Imaging showed bilateral
      cerebellopontine angle lesions and also a small mass in right lateral ventricle
      and anterior third ventricle region. The right cerebellopontine angle mass was
      surgically excised and radio- and chemotherapy given for the remaining lesions.
      This is the second case reported in the world literature. The case is discussed
      and the literature is reviewed.

PMID- 14975434
TI  - Possible participation of clip rotation in the formation of de novo aneurysm.
AB  - During long term follow-up after successful treatment of ruptured intracranial
      aneurysms, a few patients develop newly formed (de novo) aneurysms, which account
      for 0.9-1.1% of all cerebral aneurysms. As for the etiology of de novo cerebral
      saccular aneurysms, hemodynamic stress is considered to be the most important
      factor. The woman whose case we present here had developed a ruptured anterior
      communicating aneurysm at the age of 52, and the aneurysm with its anterior
      projection was completely clipped. Eight years later, she suffered
      intraventricular hemorrhage. Angiogram showed a newly formed anterior
      communicating artery aneurysm, which projected to the side opposite the clip.
      Surgical exploration found the head of the clip had rotated and become trapped
      between optic nerves. We speculated the rotation of the clip used for the
      aneurysm at the first operation was one of the possible mechanisms, which caused
      a change in the direction of hemodynamics to the anterior communicating artery,
      leading to the development of de novo aneurysm. Every neurosurgeon should pay
      attention to the clip position until dural closure has been completed.

PMID- 14975435
TI  - Long-term efficacy of surgical clipping for cerebral aneurysms.

PMID- 14975436
TI  - Subarachnoid haemorrhage due to a dissecting aneurysm of the anterior cerebral
      artery: a case report.
AB  - Dissecting aneurysms of the intracranial carotid circulation are becoming
      increasingly recognised as a cause of subarachnoid haemorrhage. We present a case
      where SAH caused by anterior cerebral artery dissection was diagnosed on a repeat
      angiogram and successfully treated by surgical trapping. Diagnosis may be
      difficult as angiographic signs may be subtle and variable. Accurate diagnosis
      and prompt treatment is important, as the re-bleed rate is high.

PMID- 14975437
TI  - Cavernous haemangioma of the internal auditory canal: a case report.
AB  - We report a patient with a cavernous haemangioma of the internal auditory canal
      (IAC). A 47-year-old man presented with a left profound hearing loss and a left
      facial palsy that had progressed over 5 years. With a preoperative diagnosis of
      acoustic or facial nerve neurinoma, the tumour was removed totally by a
      translabyrinthine approach. Intraoperatively, the tumour appeared red; it
      compressed the facial and cochlear nerves, and adhered to the vestibular nerve.
      The tumour was diagnosed as a cavernous haemangioma upon histologic and
      immunohistochemical examination. No recurrence of tumour occurred, but hearing
      loss and left facial palsy persisted. Although cavernous haemangiomas of the IAC
      is found in small size less than 10 mm, they often cause severe hearing loss and
      facial palsy. Our patient had no improvement of facial palsy, but many reports
      describe recovery of facial nerve function.

PMID- 14975438
TI  - C1-C2 tuberculosis: a case report.
AB  - Tuberculosis of the atlantoaxial spine is a rare condition that is often
      overlooked and remains a diagnostic dilemma. We report the rare case of a 56-year
      old woman with cervical myelopathy secondary to a lytic lesion of C1-C2 complex
      with a histological diagnosis of tuberculosis.

PMID- 14975439
TI  - Identification and removal of an epileptogenic lesion using Ictal-EEG, functional
      neuronavigation and electrocorticography.
AB  - PURPOSE: Cases with intractable epilepsy may present with multiple lesions in
      their brains. Ictal-EEG carries a great value in identification of the primary
      epileptogenic source. On the other hand, removal of low-grade tumors located
      around the eloquent cortex may be risky with conventional techniques. Functional
      neuronavigation (f-NN) is the integration of functional magnetic resonance
      imaging and stereotactic technologies; and provides interactive data regarding
      localization of the motor cortex. This report presents a case with
      dysembryoplastic neuroepithelial tumor (DNET), which was removed using f-NN and
      electrocorticography (ECoG) techniques. METHODS: A 19-year-old patient with
      intractable complex partial and secondary generalized seizures is presented. MRI
      revealed a low-grade tumor located in right parietal region just behind the motor
      cortex, and a contralateral temporal arachnoid cyst. Ictal-EEG demonstrated the
      right parietal origin of the seizures. The patient underwent a right parietal
      craniotomy and tumor excision using f-NN and ECoG techniques intraoperatively.
      ECoG findings correlated with epileptogenicity of the parietal lesion. RESULTS:
      Postoperative course was uneventful. No postoperative deficit was observed. The
      patient was seizure free in eight months follow-up. Pathological examination
      reported the lesion as DNET. CONCLUSIONS: Ictal-EEG has a very important role in
      identification of the epileptogenic focus in cases with multiple brain lesions.
      Preservation of the functional cortex is the most prominent aim during lesional
      surgery of epilepsy. Intraoperative mapping using f-NN and ECoG supports the
      orientation of the neurosurgeon to the functional and epileptogenic cortical
      areas; and thus, increase the safety and efficacy of surgical procedures.

PMID- 14975440
TI  - Letter to the editor. Nocardia brain abscess misinterpreted as cerebral
      infarction.

PMID- 14975442
TI  - Physiologic, pathologic and therapeutic implications for hemoglobin interactions
      with nitric oxide.

PMID- 14975443
TI  - Hemoglobin-nitric oxide cooperativity: is NO the third respiratory ligand?
AB  - Through its cooperative binding mechanism, hemoglobin is an effective transporter
      of oxygen and carbon dioxide. Although data have recently been presented
      suggesting otherwise, the rate at which nitric oxide binds to hemoglobin is not
      cooperative. On the other hand, the rate at which nitric oxide dissociates from
      hemoglobin is cooperative so that, similar to the case of oxygen, the
      cooperativity in equilibrium ligand binding is manifested in the dissociation
      rate rather than the association rate. Two general factors that diminish the
      likelihood that hemoglobin transports nitric oxide are the slow dissociation rate
      of nitric oxide from hemoglobin and the very fast hemoglobin oxidation reaction,
      which converts nitric oxide to the inert molecule nitrate. Despite these factors
      the possibility that NO is delivered by hemoglobin under certain conditions or
      through more complicated mechanisms needs further study.

PMID- 14975444
TI  - Circulating NO pool: assessment of nitrite and nitroso species in blood and
      tissues.
AB  - The formation of nitric oxide (NO) has been linked to many regulatory functions
      in mammalian cells. With the appreciation that NO-mediated nitrosation reactions
      are involved in cell signaling and pathology there is a need to elucidate and
      better characterize the different biochemical pathways of NO in vivo. Despite
      significant methodological advances over the years one major obstacle in
      assessing the significance of nitrosated species and other NO-related metabolites
      remains: their reliable measurement in complex biological matrices. In this
      review we briefly discuss the major routes of NO metabolism and transport in the
      mammalian circulation, considering plasma, red blood cell, and tissue
      compartments separately. In addition, we attempt to give a recommendation as to
      the most appropriate analytical technique and sample processing procedures for
      the reliable quantification of either species.

PMID- 14975445
TI  - Effect of vitamin B6 on oxygen radicals, mitochondrial membrane potential, and
      lipid peroxidation in H2O2-treated U937 monocytes.
AB  - Vitamin B6 (Vit.B6) supplementation has been shown to be beneficial in reducing
      diabetic complications, cognitive aging, and in the prevention of coronary heart
      disease. It was hypothesized that Vit.B6 compounds may function as antioxidants
      and thus offer protection against oxidative stress under various
      pathophysiological and or experimental conditions. To test this hypothesis, U937
      monocytes were cultured with pyridoxine (P), pyridoxal phosphate (PP) and
      pyridoxamine (PM) and H2O2, either alone or together for 2 h. Oxidative stress
      was determined by measuring superoxide radical production, lipid peroxidation,
      and mitochondrial transmembrane potential. Results demonstrate that Vit.B6
      compounds can prevent the oxygen radical generation and lipid peroxidation caused
      by hydrogen peroxide in U937 monocytes, and that some of the protective effect of
      Vit.B6 may occur via modification of mitochondrial function.

PMID- 14975446
TI  - HSP25 overexpression attenuates oxidative stress-induced apoptosis: roles of
      ERK1/2 signaling and manganese superoxide dismutase.
AB  - HSP25 has been shown to induce resistance to radiation and oxidative stress;
      however, its exact mechanisms remain unclear. In the present study, a high
      concentration of H2O2 was found to induce DNA fragmentation in L929 mouse
      fibroblast cells, and HSP25 overexpression attenuated this phenomenon. To
      elucidate the mechanisms of H2O2-mediated cell death, ERK1/2, p38 MAPK, and
      JNK1/2 phosphorylation in the cells after treatment with H2O2 were examined.
      ERK1/2 and JNK1/2 were activated by H2O2; ERK1/2 activation was inhibited in
      HSP25-overexpressed cells, while JNK1/2 was indifferent. Inhibition of ERK1/2
      activation by treatment of the cells with PD98059 or dominant-negative ERK2
      transfection blocked H2O2-induced cell death; similarly treated HSP25
      overexpressed cells were not at all affected. Moreover, inhibition of JNK1/2 by
      dominant-negative JNK1 or JNK2 transfection did not affect H2O2-mediated cell
      death in control cells. Dominant-negative Ras or Raf transfection inhibited H2O2
      mediated ERK1/2 activation and cell death in control cells. On the contrary,
      HSP25-overexpressed cells did not show any differences. Upstream pathways of H2O2
      mediated ERK1/2 activation and cell death involved both tyrosine kinase (PDGFbeta
      receptor and Src) and PKCdelta, while in HSP25-overexpressed cells these kinases
      did not respond to H2O2 treatment. Since HSP25 overexpression reduced reactive
      oxygen species (ROS), increased manganese superoxide dismutase (MnSOD) gene
      expression, and increased enzyme activity, involvement of MnSOD in HSP25-mediated
      attenuation of H2O2-mediated ERK1/2 activation and cell death was examined.
      Blockage of MnSOD with antisense oligonucleotides prevented DNA fragmentation and
      returned the ERK1/2 activation to the control level. Indeed, when MnSOD was
      overexpressed in L929 cells, similar to in HSP25-overexpressed cells, DNA
      fragmentation and ERK1/2 activation were reduced. From the above results, we
      suggest for the first time that reduced oxidative damage by HSP25 was due to
      MnSOD-mediated downregulation of ERK1/2.

PMID- 14975447
TI  - Analysis of gene expression in neural cells subject to chronic proteasome
      inhibition.
AB  - A number of studies have suggested that proteasome inhibition plays a causal role
      in the neuropathological processes observed in aging, Alzheimer's disease (AD),
      and Parkinson's disease (PD). Although the effects of acute and toxic proteasome
      inhibition on neural viability are well documented, at present little is known
      about the effects of chronic low-level proteasome inhibition on neural
      homeostasis. In order to address this issue we have established clonal lines of
      neural SH-SY5Y cells, which were generated after continual exposure to low
      concentrations of a pharmacological proteasome inhibitor. We have recently
      utilized these clonal cell lines to demonstrate that chronic low-level proteasome
      inhibition induces neural alterations that are highly relevant to aging, AD, and
      PD. The focus of this study was to elucidate the alterations in gene expression
      that occurred in our clonal cell lines after chronic low-level proteasome
      inhibition. Taken together, data presented in this report indicate that, although
      chronic low-level proteasome inhibition alters the expression of a limited number
      of genes (less than 0.8%), it is observed to significantly alter the expression
      of genes within specific categories that are highly relevant to aging, AD, and
      PD. Perhaps just as importantly, our analysis revealed that the vast majority of
      genes altered by chronic low-level proteasome inhibition have not been
      significantly characterized, suggesting that proteasome inhibition may mediate
      effects on neural homeostasis through as yet unidentified cellular processes.

PMID- 14975448
TI  - Vitamin E delivery to human skin: studies using deuterated alpha-tocopherol
      measured by APCI LC-MS.
AB  - Enrichment of skin surface lipids with deuterium-labeled alpha-tocopherol was
      compared with plasma enrichment to evaluate kinetics of the delivery of vitamin E
      to skin surface lipids. For 7 d, subjects consumed 75 mg each of RRR-alpha-[5
      (C2H3)]- (d3) and all rac-alpha-[5,7-(C2H3)2]- (d6) tocopheryl acetates with
      breakfast. Blood was drawn and skin lipids were collected daily for 2 weeks, then
      every other day for 2 weeks. A liquid chromatography-mass spectrometry
      atmospheric pressure chemical ionization method for quantification of deuterium
      labeled (d3, d6, d9-alpha-tocopherols) and unlabeled (d0-) alpha- and gamma
      tocopherols was developed. Tocopherols were quantified at their m/z [M-1] using
      single ion recording. alpha-Tocopherol detection was linear from 1 to 100 pmol
      with a detection limit of 40 pg (93 fmol). Detection of gamma-tocopherol was
      twice as sensitive due to greater ionization efficiency. Though d3- and d6-alpha
      tocopherols appeared in plasma within 24 h of the first dose, d3-alpha-tocopherol
      was not detected in skin surface lipids until approximately 1 week. Plasma
      percentage d3 peaked at day 8, while skin surface lipid percentage d3 increased
      on average until day 19. Apparently skin employs a mechanism to deliver alpha
      tocopherol into skin via lipid secretions.

PMID- 14975449
TI  - Enhanced protein glutathiolation and oxidative stress in cigarette smokers.
AB  - There are many functional assays of oxidative damage to DNA, protein, and lipids
      but few reliable markers of chronic oxidative stress. The glutathiolation of
      proteins at key Cys residues is considered an important redox-sensitive,
      posttranslational signaling mechanism in the regulation of critical cellular
      functions. To determine whether protein bound glutathione (GSSP) is a sensitive
      indicator of oxidative stress, red blood cell and plasma concentrations were
      measured and compared between smokers and nonsmokers. In a community-based study
      conducted in Westchester County, New York, USA, blood samples were obtained from
      354 cigarette smokers and 97 never smokers. The mean concentration of blood GSSP
      (micromol/L) was 32% higher in cigarette smokers and 43% higher when standardized
      by hemoglobin concentrations (p <.01). Plasma GSSP levels were also 20% higher in
      smokers than in nonsmokers (p <.001). The relationship was dose-dependent, with
      blood GSSP levels significantly correlated with cigarettes smoked per day, plasma
      cotinine, and plasma thiocyanate (r values ranged from .25 to .40). In smokers,
      there were no significant differences in GSSP and GSH levels by GSTM1 or GSTM3
      genotype. Intraindividual variation in blood samples, as determined by taking
      serial samples over a 2-week period, was low (CV = 12.1%, n = 8). GSSP levels are
      stable over time but increase in response to the abundant free radicals in
      cigarette smoke. These findings support the use of GSSP as a sensitive biomarker
      of oxidative stress.

PMID- 14975450
TI  - Reactions of desferrioxamine with peroxynitrite-derived carbonate and nitrogen
      dioxide radicals.
AB  - The iron chelating agent desferrioxamine inhibits peroxynitrite-mediated
      oxidations and attenuates nitric oxide and oxygen radical-dependent oxidative
      damage both in vitro and in vivo. The mechanism of protection is independent of
      iron chelation and has remained elusive over the past decade. Herein, stopped
      flow studies revealed that desferrioxamine does not react directly with
      peroxynitrite. However, addition of peroxynitrite to desferrioxamine in both the
      absence and the presence of physiological concentrations of CO2 and under excess
      nitrite led to the formation of a one-electron oxidation product, the
      desferrioxamine nitroxide radical, consistent with desferrioxamine reacting with
      the peroxynitrite-derived species carbonate (CO3*-) and nitrogen dioxide (*NO2)
      radicals. Desferrioxamine inhibited peroxynitrite-dependent free radical-mediated
      processes, including tyrosine dimerization and nitration, oxyhemoglobin oxidation
      in the presence of CO2, and peroxynitrite plus carbonate-dependent
      chemiluminescence. The direct two-electron oxidation of glutathione by
      peroxynitrite was unaffected by desferrioxamine. The reactions of desferrioxamine
      with CO3*- and *NO2 were unambiguously confirmed by pulse radiolysis studies,
      which yielded second-order rate constants of 1.7 x 10(9) and 7.6 x 10(6) M(-1) s(
      1), respectively. Desferrioxamine also reacts with tyrosyl radicals with k = 6.3
      x 10(6) M(-1) s(-1). However, radical/radical combination reactions between
      tyrosyl radicals or of tyrosyl radical with *NO2 outcompete the reaction with
      desferrioxamine and computer-assisted simulations indicate that the inhibition of
      tyrosine oxidation can be fully explained by scavenging of the peroxynitrite
      derived radicals. The results shown herein provide an alternative mechanism to
      account for some of the biochemical and pharmacological actions of
      desferrioxamine via reactions with CO3*- and *NO2 radicals.

PMID- 14975451
TI  - Protective mechanisms against peptide and protein peroxides generated by singlet
      oxygen.
AB  - Reaction of certain amino acids, peptides, and proteins with singlet oxygen
      yields substrate-derived peroxides. Recent studies have shown that these species
      are formed within intact cells and can inactivate key cellular enzymes. This
      study examines potential mechanisms by which cells might remove or detoxify such
      peroxides. It is shown that catalase, horseradish peroxidase, and Cu/Zn
      superoxide dismutase do not react rapidly with these peroxides. Oxymyoglobin and
      oxyhemoglobin, but not the met (Fe3+) forms of these proteins, react with peptide
      but not protein, peroxides with oxidation of the heme iron. Glutathione
      peroxidase, in the presence of reduced glutathione (GSH) rapidly removes peptide,
      but not protein, peroxides, consistent with substrate size being a key factor.
      Protein thiols, GSH, other low-molecular-weight thiols, and the seleno-compound
      ebselen react, in a nonstoichiometric manner, with both peptide and protein
      peroxides. Cell lysate studies show that thiol consumption and peroxide removal
      occur in parallel; the stoichiometry of these reactions suggests that thiol
      groups are the major direct, or indirect, reductants for these species. Ascorbic
      acid and some derivatives can remove both the parent peroxides and radicals
      derived from them, whereas methionine and the synthetic phenolic antioxidants
      Probucol and BHT show little activity. These studies show that cells do not have
      efficient enzymatic defenses against protein peroxides, with only thiols and
      ascorbic acid able to remove these materials; the slow removal of these species
      is consistent with protein peroxides playing a role in cellular dysfunction
      resulting from oxidative stress.

PMID- 14975452
TI  - Repair of peroxynitrite damage to tubulin by the thioredoxin reductase system.
AB  - Cumulative oxidative damage to proteins coupled with a decrease in repair has
      been implicated in the pathology of several neurodegenerative diseases. Herein we
      report that peroxynitrite-induced disulfides in porcine brain tubulin are
      repaired by the thioredoxin reductase system composed of rat liver thioredoxin
      reductase, human or Escherichia coli thioredoxin, and NADPH. Disulfide bonds
      between the alpha-tubulin and the beta-tubulin subunits were repaired by
      thioredoxin reductase as determined by Western blot under nonreducing conditions.
      Total disulfide repair by thioredoxin reductase was assessed using a sulfhydryl
      specific labeling reagent, 5-iodoacetamido-fluorescein. Treatment of tubulin with
      1.0 mM peroxynitrite anion decreased 5-iodoacetamido-fluorescein labeling by 48%;
      repair of peroxynitrite-damaged tubulin with thioredoxin reductase restored
      sulfhydryl labeling to control levels. Tubulin disulfide reduction by thioredoxin
      reductase restored tubulin polymerization activity that was lost after
      peroxynitrite was added. The extent of activity restored by thioredoxin reductase
      and by the nonspecific disulfide-reducing agent tris(2-carboxyethyl)phosphine
      hydrochloride was identical; however, activity was not restored to control
      levels. Tyrosine nitration of tubulin was detected at all concentrations of
      peroxynitrite tested; thus, tubulin nitration may be responsible for the fraction
      of activity that could not be restored. Thiol-disulfide exchange between tubulin
      and thioredoxin was detected by Western blot, thereby providing further support
      for our observations that optimal repair of tubulin disulfides required
      thioredoxin.

PMID- 14975453
TI  - Depletion of deoxyribonucleoside triphosphate pools in tumor cells by nitric
      oxide.
AB  - Nitric oxide displays pro- and anti-tumor activities, prompting further studies
      to better understand its precise role. Nitric oxide inhibits ribonucleotide
      reductase (RnR), the limiting enzyme for de novo dNTP synthesis. We report here
      the first detailed analysis of dNTP variations induced in tumor cells by NO. NO
      prodrugs induced a depletion in dNTP pools and an activation of the pyrimidine
      salvage pathway, as did hydroxyurea, the prototypic RnR inhibitor. In the
      presence of dipyridamole, which blocked salvaged dNTP synthesis, depletion of
      dNTP pools was also observed in tumor cells cocultured with macrophages
      expressing the high-output iNOS activity. This effect was rapid, reversible,
      blocked by NO scavengers, and cGMP independent. It was quantitatively correlated
      to iNOS activity. In the absence of dipyridamole, NO still induced a decrease in
      dATP concentration in tumor cells cocultured with macrophages, whereas
      surprisingly, concentrations of dCTP and dTTP expanded considerably, resulting in
      a strong imbalance in dNTP pools. NO prodrugs did not cause such an increase in
      pyrimidine dNTP, suggesting that pyrimidine nucleosides were released by NO
      injured macrophages. Altered dNTP levels have been reported to promote
      mutagenesis and apoptosis. It is suggested that abnormal changes in dNTP pools in
      tumors might contribute to NO-dependent toxicity.

PMID- 14975454
TI  - Pharmacokinetic study of acyl-protected hydroxylamine probe, 1-acetoxy-3
      carbamoyl-2,2,5,5-tetramethylpyrrolidine, for in vivo measurements of reactive
      oxygen species.
AB  - 1-Acetoxy-3-carbamoyl-2,2,5,5-tetramethylpyrrolidine (ACP) is a unique probe for
      in vivo measurements of reactive oxygen species (ROS), because it is hydrolyzed
      by esterase to a hydroxylamine form (CP-H), which is oxidized to an electron spin
      resonance-detectable nitroxyl radical (CP) by a reaction with superoxide anion
      radical, etc. Although a knowledge of pharmacokinetics is essential for the use
      of ACP in vivo, such information is limited. We investigated the pharmacokinetics
      of ACP in mice by examining the time course of the tissue distribution of ACP, CP
      H, and CP after intravenous or intraperitoneal injection of ACP. Esterase
      activity for ACP in tissue homogenates was also measured. The concentration of
      ACP decreased in all tissues obeying a one-compartment model. ACP was hydrolyzed
      to CP-H in the liver and kidney predominantly, and the first-pass effect of liver
      on the hydrolysis of ACP was very large. A homogeneous biodistribution of CP-H
      was obtained 10 min after the injection of ACP regardless of the injection route,
      and concentrations remained stable over at least 20 min. Because of these
      pharmacokinetic properties, ACP should be suitable for the imaging of ROS in
      animals.

PMID- 14975455
TI  - Paradigm shifts in cardiovascular medicine.
AB  - Cardiovascular medicine is changing rapidly with the development, testing, and
      introduction of new diagnostic and therapeutic methods. New interventional
      techniques such as the use of drug-eluting stents have important implications for
      the care of individual patients and the delivery and economics of health care in
      general. Drug-eluting stents have been shown to improve outcomes among patients
      undergoing percutaneous coronary intervention by significantly reducing
      restenosis rates. Two randomized trials have documented that per 100 patients
      treated with the sirolimus drug-eluting stent, 12.5 to 13.6 patients avoided the
      need for subsequent target lesion revascularization, when compared with patients
      treated with conventional stents. The economic effect of the introduction of
      these stents, which are projected to be two to three times as expensive as
      conventional stents, is complex and depends on which segment of health care is
      considered. These stents will be favorably received by patients, physicians,
      employers, and society as well as payers. However, hospitals may be adversely
      affected by having increased procedural costs for the stents, along with fewer
      procedures for evaluation and treatment of restenosis and probably decreased
      surgical volumes. Drug-eluting stents are only the first of many new technologic
      advances that will affect cardiovascular care. These procedures have many
      features in common, including: 1). replacement of major surgical procedures with
      less invasive approaches; and 2). redistribution of costs, with a decrease in
      hospital profits but potentially lower costs of health care delivery for society
      as a whole.

PMID- 14975456
TI  - Can we afford to eliminate restenosis? Can we afford not to?
AB  - Over the past decade, coronary stenting has emerged as the dominant form of
      percutaneous coronary revascularization. However, bare metal stents remain
      limited by a high incidence of restenosis, leading to frequent repeat
      revascularization procedures and substantial economic burden. Antiproliferative
      drug-eluting stents (DES) have recently demonstrated dramatic reductions in rates
      of restenosis, compared with conventional stenting, but important concerns about
      their costs have been raised. In this article, we summarize current evidence on
      the economic impact of restenosis and explore the potential benefits and economic
      outcomes of DES. In addition to examining the long-term costs of this promising
      technology, we consider the potential cost-effectiveness of DES from a health
      care system perspective and the impact of specific patient, lesion, and provider
      characteristics on these parameters.

PMID- 14975457
TI  - Nonsteroidal anti-Inflammatory drugs and cardiovascular risk.
AB  - Nonsteroidal anti-inflammatory drugs (NSAID) inhibit cyclooxygenase (COX)
      enzymes, which exist in at least two isoforms, COX-1 and COX-2. Aspirin and older
      agents in this class are nonselective inhibitors of both COX-1 and COX-2. Newer
      agents termed "coxibs" are selective inhibitors of COX-2. Among the NSAID, only
      aspirin has been proven to significantly reduce cardiovascular risk, primarily
      through inhibition of COX-1-mediated platelet aggregation. It has been suggested
      that other nonselective agents, especially naproxen, may provide some lesser
      degree of cardioprotection, but conclusive evidence is lacking. Conversely, there
      are concerns that the COX-2 inhibitors may increase cardiovascular risk. However,
      mechanisms for this potentially adverse cardiovascular effect are unknown, and it
      is becoming increasingly clear that our understanding of the role of COX-2 in
      cardiovascular function is incomplete. Some studies have demonstrated a
      potentially beneficial effect of COX-2 on cardiovascular function that could be
      negated by COX-2 inhibition, while other studies have reported improved
      endothelial function with COX-2 inhibitors. Additionally, the impact of combined
      therapy with aspirin and other COX inhibitors is not yet clear. This article will
      review the studies that have examined these issues.

PMID- 14975458
TI  - Optimal suppression of thromboxane A(2) formation by aspirin during percutaneous
      transluminal coronary angioplasty: no additional effect of a selective
      cyclooxygenase-2 inhibitor.
AB  - OBJECTIVES: We examined the contribution of cyclooxygenase (COX)-1 and -2 to the
      generation of prostacyclin, thromboxane (Tx) A(2), and 8-epi prostaglandin (PG)
      F(2alpha) during percutaneous transluminal coronary angioplasty (PTCA).
      BACKGROUND: Both TxA(2) and 8-epi PGF(2alpha) activate platelets and are
      mitogenic, whereas prostacyclin is a platelet inhibitor, and therefore may
      influence the outcome of PTCA. METHODS: Twenty-one patients undergoing PTCA while
      receiving aspirin 300 mg daily or aspirin plus the selective COX-2 inhibitor
      nimesulide were compared with 13 patients treated only with fradafiban, a
      glycoprotein IIb/IIIa antagonist. Urine was analyzed for the metabolites of
      TxA(2) (Tx-M) and prostacyclin (PGI-M) and for the isoprostane, 8-epi
      PGF(2alpha). RESULTS: In the fradafiban group, there was a marked increase in Tx
      M during PTCA (mean, 1973; 95% confidence interval [CI] 112 to 3834 rising to
      mean 7645; 95% CI 2,009 to 13281 pg/mg creatinine, p = 0.018). The Tx-M excretion
      was similarly reduced by aspirin and the combination of aspirin and nimesulide.
      In contrast, the combination of nimesulide and aspirin inhibited PGI-M excretion
      to a greater extent than aspirin (p = 0.001). Urinary 8-epi PGF(2alpha) excretion
      was elevated following PTCA compared with normal subjects (p = 0.002) and
      appeared to be unaffected by any of the treatments. CONCLUSIONS: The increase in
      TxA(2) during PTCA is primarily COX-1 dependent, and aspirin alone is effective
      in suppressing its formation. In contrast, prostacyclin generation is both COX-1
      and COX-2 dependent. The inhibition of COX-1 and COX-2 did not prevent the
      production of 8-epi PGF(2alpha), suggesting that this is not enzymatically
      derived. The persistent generation of 8-epi PGF(2alpha) may contribute to the
      thrombosis and restenosis that complicate PTCA.

PMID- 14975459
TI  - Cyclooxygenase inhibition in patients with coronary artery disease.

PMID- 14975460
TI  - Short- and long-term recovery of left ventricular function predicted at the time
      of primary percutaneous coronary intervention in anterior myocardial infarction.
AB  - OBJECTIVES: The aim of this study was to determine predictors of left ventricular
      (LV) function recovery at the time of primary percutaneous coronary intervention
      (PCI). BACKGROUND: Angiographic, intracoronary Doppler flow, and
      electrocardiographic variables have been reported to be predictors of recovery of
      LV function after acute myocardial infarction (MI). We directly compared the
      predictive value of Thrombolysis In Myocardial Infarction (TIMI) flow grade,
      corrected TIMI frame count (cTfc), myocardial blush grade, coronary Doppler flow
      velocity analysis, and resolution of ST-segment elevation for recovery of LV
      function in patients undergoing primary PCI for acute MI. METHODS: We
      prospectively studied 73 patients who underwent PCI for an acute anterior MI.
      Recovery of global and regional LV function was measured using an
      echocardiographic 16-segment wall motion index (WMI) before PCI, at 24 h, at one
      week, and at six months. Directly after successful PCI, coronary flow velocity
      reserve (CFR), cTfc, TIMI flow grade, and myocardial blush grade were assessed.
      RESULTS: Mean global and regional WMI improved gradually over time from 1.86 +/-
      0.23 before PCI to 1.54 +/- 0.34 at six-month follow-up (p < 0.0001) and from
      2.39 +/- 0.30 before PCI to 1.87 +/- 0.48 at six-month follow-up (p < 0.0001),
      respectively. Multivariate analysis revealed CFR as the only independent
      predictor for global and regional recovery of LV function at six months.
      CONCLUSIONS: Doppler-derived CFR is a better prognostic marker for LV function
      recovery after anterior MI than other currently used parameters of myocardial
      reperfusion.

PMID- 14975461
TI  - Outcome of acute ST-segment elevation myocardial infarction in diabetics treated
      with fibrinolytic or combination reduced fibrinolytic therapy and platelet
      glycoprotein IIb/IIIa inhibition: lessons from the GUSTO V trial.
AB  - OBJECTIVES: We studied the outcome of diabetics enrolled in the Global Use of
      Strategies to Open Occluded Coronary Arteries (GUSTO) V trial to assess whether
      the combination of half-dose reteplase and abciximab provides any propitious
      benefits over standard fibrinolytic therapy in diabetic patients. BACKGROUND:
      Diabetics with acute ST-segment elevation myocardial infarction (MI) have a worse
      outcome compared with nondiabetics. Higher-risk patients are usually more likely
      to benefit from advances in medical therapy. METHODS: We analyzed diabetic
      patients enrolled in the GUSTO V trial to assess the outcome of those randomized
      to the combination of half-dose reteplase and abciximab versus those randomized
      to reteplase. We also evaluated whether any differences existed in presentation
      and outcome of MI among the diabetics versus the nondiabetics enrolled in the
      study. RESULTS: The trial enrolled 13782 nondiabetics and 2633 diabetics.
      Compared to nondiabetics, diabetics had a significantly higher mortality at 30
      days (8.5% vs. 5.1%, p < 0.001) and at 1 year (12.7% vs. 7.5%, p < 0.001). Among
      the diabetic subset, no significant difference existed in the incidence of 30-day
      (8.8% vs. 8.2%, p = 0.52) or 1-year mortality (13.0% vs. 12.4%, p = 0.62) among
      patients randomized to reteplase compared to those receiving combination of
      abciximab and reteplase. The incidence of reinfarction (2.5% vs. 4.3%, p =
      0.013), recurrent ischemia (11.8% vs. 14.9%, p = 0.017), and urgent
      revascularization (10.9% vs. 13.3%, p = 0.055) at seven days was lower in
      diabetics treated with the combination therapy. CONCLUSIONS: Compared to
      nondiabetics, diabetics continue to have a worse outcome with MI. Although
      combination therapy did not provide a survival benefit, nonfatal ischemic
      outcomes, including reinfarction, recurrent ischemia, and urgent
      revascularization, were substantially reduced.

PMID- 14975462
TI  - Improved speed and stability of ST-segment recovery with reduced-dose
      tenecteplase and eptifibatide compared with full-dose tenecteplase for acute ST
      segment elevation myocardial infarction.
AB  - OBJECTIVES: This sub-study of the Integrilin and Tenecteplase in Acute Myocardial
      Infarction (INTEGRITI) trial evaluated of the impact of combination reperfusion
      therapy with reduced-dose tenecteplase plus eptifibatide on continuous ST-segment
      recovery and angiographic results. BACKGROUND: Combination therapy with reduced
      dose fibrinolytics and glycoprotein IIb/IIIa inhibitors for ST-segment elevation
      myocardial infarction improves biomarkers of reperfusion success but has not
      reduced mortality when compared with full-dose fibrinolytics. METHODS: We
      evaluated 140 patients enrolled in the INTEGRITI trial with 24-h continuous 12
      lead ST-segment monitoring and angiography at 60 min. The dose-combination
      regimen of 50% of standard-dose tenecteplase (0.27 microg/kg) plus high-dose
      eptifibatide (2 boluses of 180 microg/kg separated by 10 min, 2.0 microg/kg/min
      infusion) was compared with full-dose tenecteplase (0.53 microg/kg). RESULTS: The
      dose-confirmation regimen of reduced-dose tenecteplase plus high-dose
      eptifibatide was associated with a faster median time to stable ST-segment
      recovery (55 vs. 98 min, p = 0.06), improved stable ST-segment recovery by 2 h
      (89.6% vs. 67.7%, p = 0.02), and less recurrent ischemia (34.0% vs. 57.1%, p =
      0.05) when compared with full-dose tenecteplase. Continuously updated ST-segment
      recovery analyses demonstrated a modest trend toward greater ST-segment recovery
      at 30 min (57.7% vs. 40.6%, p = 0.13) and 60 min (82.7% vs. 65.6%, p = 0.08) with
      this regimen. These findings correlated with improved angiographic results at 60
      min. CONCLUSIONS: Combination therapy with reduced-dose tenecteplase and
      eptifibatide leads to faster, more stable ST-segment recovery and improved
      angiographic flow patterns, compared with full-dose tenecteplase. These findings
      question the relationship between biomarkers of reperfusion success and clinical
      outcomes.

PMID- 14975463
TI  - A comparison of short- and long-term outcomes after off-pump and on-pump coronary
      artery bypass graft surgery with sternotomy.
AB  - OBJECTIVES: This study was designed to compare in-hospital mortality and
      complications and three-year mortality and revascularization for off-pump and on
      pump coronary artery bypass graft (CABG) surgery after adjusting for patient
      risk. BACKGROUND: The use of off-pump CABG surgery has increased tremendously in
      recent years, but little is known about its long-term outcomes relative to on
      pump CABG surgery, and most studies have been very small. METHODS: Short- and
      long-term outcomes (inpatient mortality and complications, three-year risk
      adjusted mortality, and mortality/revascularization) were explored for patients
      who underwent off-pump CABG surgery (9135 patients) and on-pump CABG surgery
      (59044 patients) with median sternotomy from 1997 to 2000 in the state of New
      York. RESULTS: Risk-adjusted inpatient mortality was 2.02% for off-pump versus
      2.16% for on-pump (p = 0.390). Off-pump patients had lower rates of perioperative
      stroke (1.6% vs. 2.0%, p = 0.003) and bleeding requiring reoperation (1.6% vs.
      2.2%, p < 0.001) and higher rates of gastrointestinal bleeding, perforation, or
      infarction (1.2% vs. 0.9%, p = 0.003). Off-pump patients had lower postoperative
      lengths of stay (median 5 days vs. 6 days, p < 0.001). On-pump patients had
      higher three-year survival (adjusted risk ratio [RR] =1.086, p = 0.045) and
      higher freedom from death or revascularization (adjusted RR = 1.232, p < 0.001).
      When analyses were limited to 1999 to 2000, the two-year adjusted hazard ratio
      for survival was not significant (adjusted RR = 0.99, p = 0.81). CONCLUSIONS: On
      pump patients experience better long-term survival and freedom from
      revascularization than off-pump patients. However, the survival benefit from on
      pump procedures was no longer present in the last two years of the study.

PMID- 14975464
TI  - Heart rate-corrected QT interval prolongation predicts risk of coronary heart
      disease in black and white middle-aged men and women: the ARIC study.
AB  - OBJECTIVES: We aimed to study the predictive value of heart rate-corrected QT
      interval (QTc) for incident coronary heart disease (CHD) and cardiovascular
      disease (CVD) mortality in the black and white general population, and to
      validate various QT measurements. BACKGROUND: QTc prolongation is associated with
      higher risk of mortality in cardiac patients and in the general population.
      Little is known about the association with incident CHD. No previous studies
      included black populations. METHODS: We studied the predictive value of QTc
      prolongation in a prospective population study of 14,548 black and white men and
      women, age 45 to 64 year. QT was determined by the NOVACODE program in the
      digital electrocardiogram recorded at baseline. RESULTS: In quintiles of QTc,
      cardiovascular risk profile deteriorated with longer QTc, and risk of CHD and CVD
      mortality increased. The high risk in the upper quintile was mostly explained by
      the 10% with the longest QTc. The age-, gender-, and race-adjusted hazard ratios
      for CVD mortality and CHD in subjects with the longest 10% relative to the other
      90% of the gender-specific QTc distribution were 5.13 (95% confidence interval
      3.80 to 6.94) and 2.14 (95% confidence interval 1.71 to 2.69), respectively. The
      increased risk was partly, but not completely, attributable to other risk factors
      or the presence of chronic disease. The association was stronger in black than in
      white subjects. Manual- and machine-coded QT intervals were highly correlated,
      and the method of rate correction did not affect the observed associations.
      CONCLUSIONS: Long QTc is associated with increased risk of CHD and CVD mortality
      in black and white healthy men and women.

PMID- 14975465
TI  - QT interval prolongation and prognosis: further validation of the quantitative
      approach to electrocardiography.

PMID- 14975466
TI  - The prognostic importance of comorbidity for mortality in patients with stable
      coronary artery disease.
AB  - OBJECTIVES: To identify the prevalent and prognostically important coexisting
      illnesses among single coronary artery disease (CAD) patients. BACKGROUND: As the
      population ages, physicians are increasingly required to make decisions
      concerning patients with multiple co-existing illnesses (comorbidity). Many
      trials of CAD therapy have excluded patients with significant comorbidity, such
      that there are limited data to guide the management of those patients. METHODS:
      To consider the long-term prognostic importance of comorbid illness, we examined
      a cohort of 1471 patients with CAD who underwent cardiac catheterization between
      1985 and 1989 and were followed up through 2000 in the Duke Databank for
      Cardiovascular Diseases. Weights were assigned to individual diseases according
      to their prognostic significance in Cox proportional hazards models, thus
      creating a new CAD-specific index. The new index was compared with the widely
      used Charlson index, according to prevalence of conditions, individual and
      overall associations with survival, and agreement. RESULTS: The Charlson index
      and the CAD-specific index were highly associated with long-term survival and
      almost equivalent to left ventricular ejection fraction. When considering the
      components of the Charlson index, diabetes, renal insufficiency, chronic
      obstructive pulmonary disease, and peripheral vascular disease had greater
      prognostic significance among CAD patients, whereas peptic ulcer disease,
      connective tissue disease, and lymphoma were less significant. Hemiplegia,
      leukemia, lymphoma, severe liver disease, and acquired immunodeficiency syndrome
      were rarely identified among patients undergoing coronary angiography.
      CONCLUSIONS: Comorbid disease is strongly associated with long-term survival in
      patients with CAD. These data suggest co-existing illnesses should be measured
      and considered in clinical trials, disease registries, quality comparisons, and
      counseling of individual patients.

PMID- 14975467
TI  - Comorbidity and outcome in patients with coronary artery disease.

PMID- 14975468
TI  - Diabetes mellitus: the major risk factor in unstable coronary artery disease even
      after consideration of the extent of coronary artery disease and benefits of
      revascularization.
AB  - OBJECTIVES: This study was designed to study the influence of diabetes on the
      outcome of unstable coronary artery disease (CAD). BACKGROUND: Diabetes mellitus
      is a major contributor to CAD. Despite improvement in the management of patients
      with unstable coronary syndromes, this condition is still linked to a
      substantially increased mortality and morbidity among diabetic patients. Recent
      evidence advocates early revascularization in unstable coronary syndromes.
      Diabetic patients subjected to coronary interventions under stable conditions
      have a higher risk for complications and a more dismal prognosis than nondiabetic
      subjects. Accordingly, it is of considerable interest to obtain further
      information regarding the best possible management of diabetic patients with
      unstable CAD. METHODS: A total of 2158 patients without and 299 with diabetes
      mellitus were randomized to an early invasive or a noninvasive strategy. The
      severity of CAD was expressed as the number and extent of vessel involvement.
      RESULTS: Three-vessel disease was diagnosed in 42% of diabetic and 31% of
      nondiabetic patients (p = 0.006). The percentages of patients with ST-depression
      and troponin-T >0.03 microg/l at admission were comparable among diabetic and
      nondiabetic patients. Mortality and reinfarction after 12 months were more
      frequent among diabetic than nondiabetic patients in both treatment groups.
      Diabetes remained a strong independent predictor for death and myocardial
      infarction in multivariable analysis. The invasive strategy reduced event rate in
      nondiabetic patients from 12.0% to 8.9% (odds ratio [OR] = 0.72; confidence
      interval [CI] 0.54 to 0.95; p = 0.019) and in diabetic patients from 29.9% to
      20.6% (OR 0.61; CI 0.36 to 1.04; p = 0.066). In a multivariate analysis including
      the extent of CAD, diabetes remained a strong independent predictor of the
      combined end point (relative risk [RR] 2.40; CI 1.47 to 3.91; p = 0.0001) and of
      mortality (RR 5.43; CI 2.09 to 14.12; p = 0.001). CONCLUSIONS: An invasive
      strategy improved outcome for both diabetic and nondiabetic patients with
      unstable CAD. However, diabetes mellitus remained an independent and important
      risk factor for death and myocardial infarction in the invasive group. Thus,
      factors beyond the extent of flow-limiting coronary lesions are of considerable
      importance for outcome in diabetic subjects with unstable coronary syndromes.

PMID- 14975469
TI  - Ischemic and viable myocardium in patients with non-Q-wave or Q-wave myocardial
      infarction and left ventricular dysfunction: a clinical study using positron
      emission tomography, echocardiography, and electrocardiography.
AB  - OBJECTIVES: We investigated whether patients with non-Q-wave myocardial
      infarction (NQMI) have more ischemic viable myocardium (IVM) than patients with Q
      wave myocardial infarction (QMI). BACKGROUND: Non-Q-wave myocardial infarction is
      associated with higher incidences of cardiac events than QMI, suggesting more
      myocardium at risk in NQMI. METHODS: To identify myocardial ischemia,
      hibernation, and scar, the resting and stress (82)rubidium perfusion and F-18
      fluorodeoxyglucose metabolic positron emission tomographic imaging (PET) was
      performed in 64 consecutive patients with NQMI (n = 21) or QMI (n = 43).
      Echocardiography was performed for assessment of left ventricular function and
      wall motion index (WMI). The relationships between PET, echocardiographic, and
      electrocardiographic findings were analyzed. RESULTS: There were no significant
      differences in left ventricular ejection fraction (LVEF) between NQMI and QMI
      groups (28 +/- 10% vs. 25 +/- 11%, p > 0.05). Ischemic and viable myocardium was
      more common in NQMI than in QMI (91% vs. 61%, p < 0.05). The total amount of IVM
      was significantly higher in NQMI than in QMI (6.5 +/- 5.2 vs. 2.9 +/- 2.8
      segments, p < 0.001). Neither the number of Q waves, residual ST-segment
      depression of >or=0.5 mm or elevation of >or=1 mm, nor LVEF and WMI were
      significant predictors for IVM. Wall motion index correlated with scar segments
      (r = 0.54, p < 0.001) and LVEF (r = -0.67, p < 0.001). CONCLUSIONS: Ischemic and
      viable myocardium is common in patients with NQMI and left ventricular
      dysfunction, suggesting that aggressive approaches should be taken to salvage the
      myocardium at risk in such patients.

PMID- 14975470
TI  - Akinesia becoming dyskinesia after exercise testing: prevalence and relationship
      to clinical outcome.
AB  - OBJECTIVES: The aim of this study was to determine the prevalence and prognostic
      implications of dyskinesia developing after exercise. BACKGROUND: The prevalence
      and prognostic implications of new-onset dyskinesia with exercise testing have
      not been previously described. METHODS: We considered 1005 consecutive patients
      who underwent exercise echocardiography and had akinetic segments at rest.
      Patients were divided according to the presence or absence of exercise-induced
      dyskinesia. Baseline clinical and echocardiographic parameters were compared, and
      patients were followed up for a median of 2.7 years. RESULTS: One hundred four
      (10%) patients developed dyskinesia after exercise. Compared to patients with
      segments that remained akinetic, these patients were more likely to have
      electrocardiographic (ECG) evidence of prior myocardial infarction and, during
      exercise, had a less pronounced rise in systolic blood pressure and more often
      had ECG evidence of ischemia. Their resting left ventricular (LV) ejection
      fraction was worse and improved little after exercise. However, all-cause
      mortality and the incidence of major adverse cardiac events were similar in the
      two groups, even after correction for age, gender, and resting LV function
      (hazard ratio for major adverse cardiac events = 1.36, 95% confidence interval
      [CI] 0.82 to 2.26, p = 0.23; hazard ratio for total mortality = 1.20, 95% CI 0.75
      to 1.94, p = 0.45). CONCLUSIONS: One in 10 patients with akinetic myocardium at
      rest will develop dyskinesia after exercise. This is associated with poorer LV
      function at rest and little improvement in systolic function after exercise.
      However, this response has no impact on prognosis.

PMID- 14975471
TI  - Treadmill scores in elderly men.
AB  - OBJECTIVES: This study seeks to further characterize the role of exercise testing
      in the elderly for prognosis and diagnosis of coronary artery disease.
      BACKGROUND: Recent exercise testing guidelines have recognized that statements
      regarding the elderly do not have an adequate evidence-based quality because the
      studies they are based on have limitations in sample size and design. The Duke
      Treadmill Score has been recommended for risk stratification, but recent evidence
      has suggested that it does not function in the elderly. METHODS: The study
      population consisted of male veterans (1872 patients >or=65 years; 3798 patients
      <65 years) who underwent routine clinical exercise testing with a mean follow-up
      of six years. A subset who underwent coronary angiography as clinically indicated
      (elderly, n = 405; younger, n= 809) were included. The primary outcome for all
      subjects was cardiovascular mortality with coronary angiographic findings as the
      outcome in those selected for angiography. RESULTS: In survival analysis,
      exercise-induced ST depression was prognostic in both age groups only when
      cardiovascular death was considered as the end point. Peak metabolic equivalents
      were the most significant predictor for both age groups only when all-cause death
      was considered as the end point. New age-specific prognostic scores were
      developed and found to be predictive for cardiovascular mortality in the elderly.
      Moreover, in the angiographic subset of the elderly, a specific diagnostic score
      provided significantly better discrimination than exercise ST measurements alone.
      For any new score, there is a need for validation in another elderly population.
      CONCLUSIONS: The mortality end point affected the choice of prognostic variables.
      This study demonstrates that exercise test scores can be helpful for the
      diagnosis and prognosis of coronary disease in the elderly.

PMID- 14975472
TI  - The relative importance of vascular structure and function in predicting
      cardiovascular events.
AB  - OBJECTIVES: We sought to assess the prognostic utility of brachial artery
      reactivity (BAR) in patients at risk of cardiovascular events. BACKGROUND:
      Impaired flow-mediated vasodilation measured by BAR is a marker of endothelial
      dysfunction. Brachial artery reactivity is influenced by risk factors and is
      responsive to various pharmacological and other treatments. However, its
      prognostic importance is uncertain, especially relative to other predictors of
      outcome. METHODS: A total of 444 patients were prospectively enrolled to undergo
      BAR and follow-up. These patients were at risk of cardiovascular events, based on
      the presence of risk factors or known or suspected cardiovascular disease. We
      took a full clinical history, performed BAR, and obtained carotid intima-media
      thickness (IMT) and left ventricular mass and ejection fraction. Patients were
      followed up for cardiovascular events and all-cause mortality. Multivariate Cox
      regression analysis was performed to assess the independent association of
      investigation variables on outcomes. RESULTS: The patients exhibited abnormal BAR
      (5.2 +/- 6.1% [mean +/- SD]) but showed normal nitrate-mediated dilation (9.9 +/-
      7.2%) and normal mean IMT (0.67 +/- 0.12 mm [average]). Forty-nine deaths
      occurred over the median follow-up period of 24 months (interquartile range 10 to
      34). Patients in the lowest tertile group of BAR (<2%) had significantly more
      events than those in the combined group of highest and mid-tertiles (p = 0.029,
      log-rank test). However, mean IMT (rather than flow-mediated dilation) was the
      vascular factor independently associated with mortality, even in the subgroup (n
      = 271) with no coronary artery disease and low risk. CONCLUSIONS: Brachial artery
      reactivity is lower in patients with events, but is not an independent predictor
      of cardiovascular outcomes in this cohort of patients.

PMID- 14975473
TI  - Vascular structure versus function: is endothelial dysfunction of independent
      prognostic importance or not?

PMID- 14975474
TI  - Long-term effect of combined vitamins E and C on coronary and peripheral
      endothelial function.
AB  - OBJECTIVES: We tested whether long-term administration of antioxidant vitamins C
      and E improves coronary and brachial artery endothelial function in patients with
      coronary artery disease (CAD). BACKGROUND: Endothelial function is a sensitive
      indicator of vascular health. Oxidant stress and oxidized low-density lipoprotein
      (LDL) impair endothelial function by reducing nitric oxide bioavailability in the
      artery wall. METHODS: We randomly assigned 30 subjects with CAD to combined
      vitamin E (800 IU per day) and C (1000 mg per day) or to placebos in a double
      blind trial. Coronary artery endothelial function was measured as the change in
      coronary artery diameter to acetylcholine infusions (n = 18 patients), and
      brachial artery endothelial function was assessed by flow-mediated dilation (n =
      25 patients) at baseline and six months. Plasma markers of oxidant stress
      (oxidized LDL and autoantibodies) were also measured. RESULTS: Plasma alpha
      tocopherol (p < 0.001) and ascorbic acid (p < 0.02) increased with active
      therapy. Compared to placebo, there was no improvement in coronary and brachial
      endothelial vasomotor function over six months. Although vitamins C and E tended
      to reduce F2-isoprostanes (p = 0.065), they failed to alter oxidized LDL or
      autoantibodies to oxidized LDL. CONCLUSIONS: Long-term oral vitamins C and E do
      not improve key mechanisms in the biology of atherosclerosis or endothelial
      dysfunction, or reduce LDL oxidation in vivo.

PMID- 14975475
TI  - Predischarge B-type natriuretic peptide assay for identifying patients at high
      risk of re-admission after decompensated heart failure.
AB  - OBJECTIVES: The aim of this study was to determine the value of serial B-type
      natriuretic peptide (BNP) assay for predicting post-discharge outcome of patients
      admitted for decompensated congestive heart failure (CHF). BACKGROUND: Patients
      hospitalized for decompensated CHF are frequently re-admitted. Thus,
      identification of high-risk patients before their discharge is a major issue that
      remains challenging. B-type natriuretic peptide measurement could be useful.
      METHODS: Serial BNP measurements were performed from admission to discharge in
      two samples of consecutive patients. Survivors were monitored for six months; the
      main end point combined death or first re-admission for CHF. RESULTS: Among the
      105 survivors of the derivation study, all serial BNP values, percentage change
      in BNP levels, and predischarge Doppler mitral pattern correlated with the
      outcome. In contrast, clinical variables and left ventricular ejection fraction
      were poorly predictive. The predischarge BNP assay had the best discriminative
      power (area under the receiver operating characteristic [ROC] curve = 0.80) and
      remained the lone significant variable in multivariate analysis (hazard ratio
      [HR] = 1.14 [95% confidence interval [CI], 1.02 to 1.28], p = 0.027). Among the
      97 survivors of the validation study, the predischarge BNP assay was also the
      most predictive parameter (area under the ROC curve = 0.83). The risk of death or
      re-admission increased in stepwise fashion across increasing predischarge BNP
      ranges (p < 0.0001). After adjustment for baseline covariables, the HRs were 5.1
      [95% CI 2.8 to 9.1] for BNP levels between 350 and 700 ng/l and 15.2 [95% CI 8.5
      to 27] for BNP levels >700 ng/l, compared with BNP <350 ng/l. CONCLUSIONS: High
      predischarge BNP assay is a strong, independent marker of death or re-admission
      after decompensated CHF, more relevant than common clinical or echocardiographic
      parameters and more relevant than changes in BNP levels during acute cares.

PMID- 14975476
TI  - Statin therapy is associated with improved survival in ischemic and non-ischemic
      heart failure.
AB  - OBJECTIVES: This study aimed to investigate the impact of hydroxymethylglutaryl
      coenzyme A reductase inhibitor (statin) therapy in patients with advanced heart
      failure (HF). BACKGROUND: Although statins are known to reduce mortality in
      coronary artery disease (CAD), the impact of statin therapy in patients with HF
      has not been well studied. Both the potential risks and benefits of statins in HF
      have been described. METHODS: We studied a cohort of 551 patients with systolic
      HF (left ventricular ejection fraction [EF] <or=40%) referred to a single
      university center for clinical management and/or transplant evaluation. Survival
      without the necessity of urgent heart transplantation was determined. RESULTS:
      The patients' mean age was 52 +/- 13 years; mean EF was 25 +/- 7%. Forty-five
      percent of the cohort had CAD, and 45% were receiving statin therapy, including
      73% and 22% of CAD and non-CAD patients with HF, respectively. Patients receiving
      statins were significantly older and more likely to be male, with higher rates of
      hypertension, diabetes, and smoking. The EF and cholesterol levels were similar
      between treated and non-treated patients. Statin use was associated with improved
      survival without the necessity of urgent transplantation in both non-ischemic and
      ischemic HF patients (91% vs. 72%, p < 0.001 and 81% vs. 63%, p < 0.001 at one
      year follow-up, respectively). After risk adjustment for age, gender, CAD,
      cholesterol, diabetes, medications, hemoglobin, creatinine, and New York Heart
      Association functional class, statin therapy remained an independent predictor of
      improved survival (hazard ratio 0.41 95% confidence interval 0.18 to 0.94).
      CONCLUSIONS: Statin therapy is associated with improved survival in patients with
      ischemic and non-ischemic HF. Randomized trials are needed for confirmation of a
      therapeutic benefit.

PMID- 14975477
TI  - Magnetic resonance angiography is equivalent to X-ray coronary angiography for
      the evaluation of coronary arteries in Kawasaki disease.
AB  - OBJECTIVES: The purpose of this study was to compare the results of magnetic
      resonance angiography (MRA) with X-ray coronary angiography (XCA) in a pediatric
      population. BACKGROUND: Coronary artery abnormalities in Kawasaki disease (KD)
      develop in about 15% to 25% of young patients, mostly in the form of aneurysms.
      METHODS: Thirteen patients (12 male), age three to eight years, were studied. The
      maximal diameter and length of the aneurysm were recorded. Coronary MRA was
      performed using a 1.5 T Philips Intera CV magnetic resonance scanner with an
      electrocardiographically triggered pulse sequence. It was a three-dimensional
      segmented k-space gradient-echo sequence (TE = 2.1 ms, TR = 7.5 ms, flip angle =
      30 degrees, slice thickness = 1.5 mm) employing a T2-weighted preparation pre
      pulse and a frequency selective fat-saturation pre-pulse. Data acquisition was
      performed in mid-diastole. All scans were carried out with the patient free
      breathing using a two-dimensional real-time navigator beam. All patients
      underwent XCA within a week. RESULTS: In six patients, aneurysms of the coronary
      arteries were identified, while coronary ectasia alone was present in the
      remaining seven patients. Magnetic resonance angiography and XCA diagnosis of
      coronary artery aneurysm agreed completely. Maximal aneurysm diameter and length
      and ectasia diameter by MRA and XCA were similar. No stenotic lesion was
      identified by either technique. CONCLUSIONS: In conclusion, MRA is a reliable
      diagnostic tool, equivalent to XCA for coronary artery aneurysm identification in
      patients with KD. Magnetic resonance angiography may prove to be of great value
      for the serial non-invasive evaluation of these patients.

PMID- 14975478
TI  - Estimation of myocardial hemodynamics before and after intervention in children
      with Kawasaki disease.
AB  - OBJECTIVES: We used myocardial fractional flow reserve (FFR(myo)) and coronary
      flow reserve (CFR) to estimate cut-off values for assessment of the functional
      severity of coronary stenosis and myocardial ischemia, and we tested the
      usefulness of coronary blood hemodynamic measurements before and after plain old
      balloon angioplasty (POBA) and coronary artery bypass graft surgery (CABG).
      BACKGROUND: Fractional flow reserve and CFR are useful for assessing the
      functional severity of coronary artery stenosis, coronary microvascular
      dysfunction, and myocardial ischemia during cardiac catheterization in adults.
      However, there have been no reports on the use of these measurements in children
      with Kawasaki disease (KD). METHODS: The study group included 128 patients with
      314 coronary branches. The subjects were classified into three groups: normal
      coronary group, with 206 branches; abnormal coronary artery without ischemia
      group, with 58 branches; and ischemia group, with 50 branches. RESULTS: In each
      branch, CFR and FFR(myo) were significantly lower in the ischemia group than in
      the other groups. Cut-off values for assessing the functional severity of
      coronary stenosis and CFR were approximately equal to those obtained for adults
      (CFR: <2.0; FFR(myo): <0.75). We obtained very high sensitivity and specificity
      for estimating myocardial ischemia using CFR and FFR(myo) (CFR: 94.0% and 98.5%,
      respectively; FFR(myo): 95.7% and 99.1%, respectively). Both CFR and FFR(myo)
      were reliable indicators of coronary hemodynamics before and after POBA and CABG.
      CONCLUSIONS: Together, CFR and FFR(myo) provide a useful index for assessing the
      functional severity of coronary artery stenosis and myocardial ischemia and
      estimating the effectiveness of POBA and CABG in children with KD, the same as
      they do for adults.

PMID- 14975479
TI  - Do we have a gold standard yet?

PMID- 14975480
TI  - Characterizing the young patient with aortic dissection: results from the
      International Registry of Aortic Dissection (IRAD).
AB  - OBJECTIVES: The goal of this study was to better characterize the young patient
      with aortic dissection (AoD). BACKGROUND: Aortic dissection is unusual in young
      patients, and frequently associated with unusual presentations. METHODS: Data
      were collected on 951 patients diagnosed with AoD between January 1996 and
      November 2001. Two categories of patients, <40 years and >or=40 years, were
      compared using chi-square cross tabulations for categorical and Student t test
      for continuous data. RESULTS: Sixty-eight patients (7%) with AoD were <40 years
      of age. Compared with patients >or=40 years, younger patients were less likely to
      have a prior history of hypertension (p < 0.05); however, younger patients were
      more likely to have Marfan syndrome, bicuspid aortic valve, and prior aortic
      surgery (all, p < 0.05). Clinical presentations in the two age groups were
      similar; however, younger patients were less likely to be hypertensive (25% vs.
      45%, p = 0.003). The proximal aortas of young AoD patients were larger (all, p <
      0.05) compared with older patients. These differences in aortic size between age
      groups were not entirely related to Marfan syndrome. Mortality among young
      patients was similar to patients >or=40 years of age (22% vs. 24%, p = NS),
      irrespective of the site of dissection. CONCLUSIONS: Compared with older patients
      with AoD, young patients have unique risk factors for dissection: Marfan
      syndrome, bicuspid aortic valves, and larger aortic dimensions. Surprisingly, the
      mortality risk for young AoD patients is not lower than older AoD patients.

PMID- 14975481
TI  - Diastolic coronary vascular reserve: a new index to detect changes in the
      coronary microcirculation in hypertrophic cardiomyopathy.
AB  - OBJECTIVES: The present study introduces a modification of the diastolic coronary
      conductance concept that maintains its sensitive properties to detect changes in
      the coronary microcirculation in human hypertrophy. BACKGROUND: Decrements of
      coronary flow in hypertrophy have been explained by changes in the coronary
      microcirculation. No measure is available to detect these changes. METHODS:
      Doppler velocity catheters were introduced into the left anterior descending
      artery (LAD) and left circumflex coronary artery (LCx) of patients with
      obstructive hypertrophic cardiomyopathy (HCM) (n = 11) and into the LAD of
      cardiac transplant recipients (n = 9). The diastolic coronary conductance was
      measured at rest and after maximal hyperemia induced by a bolus injection of
      adenosine. Diastolic coronary vasodilator reserve (DCVR) was calculated as the
      hyperemic diastolic coronary conductance, divided by the coronary conductance
      during resting conditions. RESULTS: Left ventricular outflow tract gradient in
      the HCM group (83 +/- 31 mm Hg) was significantly higher (p < 0.05). Septal wall
      thickness was significantly increased (p < 0.05), while wall thickness was
      unchanged in the posterior wall of the HCM group. The coronary flow reserve was
      significantly decreased in the HCM-LCx region (to 64 +/- 7% of control) and in
      the HCM-LAD regions (to 57 +/- 7% of control). The DCVR was only decreased in the
      HCM-LAD (to 46 +/- 3% of control) and not in the HCM-LCx group (86 +/- 6%, p >
      0.05). Esmolol did affect the pressure gradient and systolic shortening, but did
      not affect the maximal diastolic conductance. CONCLUSIONS: The DCVR, in contrast
      with the coronary flow reserve, is decreased in those regions that display a
      disturbance in the microcirculation and may, therefore, offer a new way to study
      coronary adaptations in patients with hypertrophy.

PMID- 14975483
TI  - Highlights of the 2003 Transcatheter Cardiovascular Therapeutics annual meeting:
      clinical implications.

PMID- 14975482
TI  - Effect of sleep loss on C-reactive protein, an inflammatory marker of
      cardiovascular risk.
AB  - OBJECTIVES: We sought to investigate the effects of sleep loss on high
      sensitivity C-reactive protein (CRP) levels. BACKGROUND: Concentrations of high
      sensitivity CRP are predictive of future cardiovascular morbidity. In
      epidemiologic studies, short sleep duration and sleep complaints have also been
      associated with increased cardiovascular morbidity. Two studies were undertaken
      to examine the effect of acute total and short-term partial sleep deprivation on
      concentrations of high-sensitivity CRP in healthy human subjects. METHODS: In
      Experiment 1, 10 healthy adult subjects stayed awake for 88 continuous hours.
      Samples of high-sensitivity CRP were collected every 90 min for 5 consecutive
      days, encompassing the vigil. In Experiment 2, 10 subjects were randomly assigned
      to either 8.2 h (control) or 4.2 h (partial sleep deprivation) of nighttime sleep
      for 10 consecutive days. Hourly samples of high-sensitivity CRP were taken during
      a baseline night and on day 10 of the study protocol. RESULTS: The CRP
      concentrations increased during both total and partial sleep deprivation
      conditions, but remained stable in the control condition. Systolic blood pressure
      increased across deprivation in Experiment 1, and heart rate increased in
      Experiment 2. CONCLUSIONS: Both acute total and short-term partial sleep
      deprivation resulted in elevated high-sensitivity CRP concentrations, a stable
      marker of inflammation that has been shown to be predictive of cardiovascular
      morbidity. We propose that sleep loss may be one of the ways that inflammatory
      processes are activated and contribute to the association of sleep complaints,
      short sleep duration, and cardiovascular morbidity observed in epidemiologic
      surveys.

PMID- 14975484
TI  - News from the European Society of Cardiology congress in Vienna, August 30 to
      September 3, 2003.

PMID- 14975485
TI  - Early experience with percutaneous transcatheter implantation of heart valve
      prosthesis for the treatment of end-stage inoperable patients with calcific
      aortic stenosis.
AB  - OBJECTIVES: This study was done to assess the results of percutaneous heart valve
      (PHV) implantation in non-surgical patients with end-stage calcific aortic
      stenosis. BACKGROUND: Replacement of PHV has been shown to be feasible in animals
      and humans. We developed a PHV composed of three pericardial leaflets inserted
      within a balloon-expandable stainless steel stent. We report the acute and early
      follow-up results of the initial six PHV implantations. METHODS: An anterograde
      approach was used in all cases. The PHV, crimped over a 22-mm diameter balloon,
      was advanced through a 24-F sheath from the femoral vein to the aortic valve and
      delivered by balloon inflation. Clinical, hemodynamic, and echocardiographic
      outcomes were assessed serially. RESULTS: All patients were in New York Heart
      Association functional class IV. The PHV was successfully delivered in five
      patients. Early migration with subsequent death occurred in one patient who
      presented with a torn native valve. Acute hemodynamic and angiographic results
      showed no residual gradient, mild (three patients) or severe (two patients)
      aortic regurgitation, and patent coronary arteries. On echocardiography, the
      aortic valve area was increased from 0.5 +/- 0.1 cm(2) to 1.70 +/- 0.03 cm(2) and
      the aortic regurgitation was paravalvular. Marked and sustained hemodynamic and
      clinical improvement was observed after successful PHV implants. The first three
      patients died of a non-cardiac cause at 18, 4, and 2 weeks, respectively, and the
      other patients are alive at 8 weeks with no signs of heart failure. CONCLUSIONS:
      Implantation of the PHV can be achieved in patients with end-stage calcific
      aortic stenosis and might become an important therapeutic option for patients not
      amenable to surgical valve replacement.

PMID- 14975486
TI  - Short- and long-term clinical benefit of sirolimus-eluting stents compared to
      conventional bare stents for patients with acute myocardial infarction.
AB  - OBJECTIVES: This study investigated the clinical outcomes of patients with ST
      segment elevation myocardial infarction (MI) treated with sirolimus-eluting
      stents (SESs) or with conventional bare stents. BACKGROUND: The clinical impact
      of SES implantation for patients with ST-segment elevation MI is currently
      unknown. METHODS: Primary angioplasty was performed with SESs in 186 consecutive
      patients with acute MI who were compared with 183 patients treated with bare
      stents. The incidence of death, reinfarction, and repeat revascularization was
      assessed at 30 and 300 days. RESULTS: Postprocedure vessel patency, enzymatic
      release, and the incidence of short-term adverse events were similar in both the
      sirolimus and the bare stents (30-day rate of death, reinfarction, or repeat
      revascularization: 7.5% vs. 10.4%, respectively; p = 0.4). Stent thrombosis was
      not diagnosed in any patient in the sirolimus group and occurred in 1.6% of
      patients treated with bare stents (p = 0.1). At 300 days, treatment with SESs
      significantly reduced the incidence of combined adverse events (9.4% vs. 17%;
      hazard ratio [HR] 0.52 [95% confidence interval (CI) 0.30 to 0.92]; p = 0.02),
      mainly due to a marked reduction in the risk of repeat intervention (1.1% vs.
      8.2%; HR 0.21 [95% CI 0.06 to 0.74]; p = 0.01). CONCLUSIONS: Compared to
      conventional bare stents, the SESs were not associated with an increased risk of
      stent thrombosis and were effective in reducing the incidence of adverse events
      at 300 days in unselected patients with ST-segment elevation acute MI referred
      for primary angioplasty.

PMID- 14975487
TI  - Editorials: why, when, and how.

PMID- 14975488
TI  - President's page: members' benevolence stretches the ACC mission well beyond US
      borders.

PMID- 14975489
TI  - Risk of noncardiac surgery in the months following placement of a drug-eluting
      coronary stent.

PMID- 14975490
TI  - Percutaneous coronary intervention before noncardiac surgery: more threat than
      benefit?

PMID- 14975493
TI  - Neuroophthalmology: a brief Vademecum.
AB  - The stunning, intricate interaction between the visual, vestibular and optomotor
      systems--each a miracle on its own--ensures maintenance of orientation in space
      as well as visual recognition and target selection despite a host of sensory
      conflicts and adversary disturbances. Their main goals are to keep a target of
      interest on the fovea by either maintaining or shifting the direction of gaze in
      order to produce an accurate internal representation of the visual surroundings,
      in particular the selected target, and to continuously mirror the spatial
      relationship between these various visual elements and the self. Not surprising,
      the implementation of this host of elaborate neural networks encompasses almost
      every part of the brain, including the brainstem, cerebellum, extrapyramidal
      system and many areas of the cerebral cortex. Thus far, these systems are among
      the best investigated in brain research; and enormous knowledge was amassed over
      the last century employing a variety of techniques, including single cell
      recordings, eye movement studies, functional imaging and neuropsychological
      observations. In addition, this prolific line of research has enlightened many
      fundamental principles of neural and neuronal processing, which have subsequently
      enriched other fields of brain research as well as computational neuroscience,
      e.g. the discovery of receptive fields, which have now become a ubiquitous
      concept in many other areas of neurophysiology. This (improperly) brief,
      fractional and undoubtedly biased Vademecum is meant to accompany the reader into
      this marvellous field of neurophysiology and neurology. In particular, it
      stresses the clinical application of its functional neuroanatomy at the bedside,
      which, in many respects, is superior to other means of investigating a patient.

PMID- 14975494
TI  - Investigations of the human visual system using functional magnetic resonance
      imaging (FMRI).
AB  - The application of functional magnetic resonance imaging (fMRI) in studies of the
      visual system provided significant advancement in our understanding of the
      organization and functional properties of visual areas in the human cortex.
      Recent technological and methodological improvements allowed studies to correlate
      neuronal activity with visual perception and demonstrated the ability of fMRI to
      observe distributed neural systems and to explore modulation of neural activity
      during higher cognitive processes. Preliminary applications in patients with
      visual impairments suggest that this method provides a powerful tool for the
      assessment and management of brain pathologies. Recent research focuses on
      obtaining new information about the spatial localization, organization,
      functional specialization and participation in higher cognitive functions of
      visual cortical areas in the living human brain and in further establishment of
      the method as a useful clinical tool of diagnostic and prognostic significance
      for various pathologic processes affecting the integrity of the visual system. It
      is anticipated that the combined neuroimaging approach in patients with lesions
      and healthy controls will provide new insight on the topography and functional
      specialization of cortical visual areas and will further establish the clinical
      value of the method for improving diagnostic accuracy and treatment planning.

PMID- 14975495
TI  - Comparison of MRI and renal cortical scintigraphy findings in childhood acute
      pyelonephritis: preliminary experience.
AB  - OBJECTIVE: The diagnosis of acute pyelonephritis in children remains a clinical
      challenge. It may cause permanent renal scar formation and results in the chronic
      renal failure if prompt diagnosis and treatment are delayed. The purpose of this
      study is to compare magnetic resonance imaging (MRI) and renal cortical
      scintigraphy (RCS) findings in childhood acute pyelonephritis and to determine
      pyelonephritic foci in the acute phase. MATERIALS AND METHOD: Twenty children (15
      females and five males) with symptoms dysuria, enuresis, costovertebral pain,
      fever of 37.5 degrees C or more and/or positive urine culture were imaged by
      unenhanced turbo spin echo T2, spin echo T1-weighted, pre- and post-gadolinium
      inversion recovery MRI and RCS. Both imaging techniques were read independently
      by two radiologists and nuclear medicine specialists. Sensitivity and specificity
      of MRI in detecting acute pyelonephritic foci and scar lesions were calculated.
      Furthermore, in order to calculate the reliability of MRI over RCS in
      differentiating scar tissue and acute pyelonephritic foci, follow-up MRI studies
      were done in six patients after treatment of acute pyelonephritis. RESULTS:
      Sensitivity and specificity of MRI in the detection of pyelonephritic lesions
      were found to be 90.9 and 88.8%, respectively. There is no statistically
      significant difference in lesion detection between the two diagnostic modalities
      (P>0.05). CONCLUSION: Post-gadolinium MR images show significant correlation with
      RCS in the determination of renal pathology. Moreover, the ability of
      discriminating acute pyelonephritic foci and renal scar in early stages of
      disease is the superiority of MRI.

PMID- 14975496
TI  - Endovascular stent placement in the treatment of upper extremity central venous
      obstruction in hemodialysis patients.
AB  - OBJECTIVE: To evaluate the efficacy of stent placement for treating upper
      extremity central venous obstruction in chronic hemodialysis patients. METHODS
      AND MATERIAL: Between January 1999 and October 2001, we inserted metallic stents
      into the upper extremity central veins of 14 patients with shunt dysfunction
      and/or arm swelling. The indications for stent placement were stenosis or
      occlusion of the central vein in the upper extremity used for dialysis. Six of
      the individuals were diagnosed with subclavian vein stenosis, and 5 with
      brachiocephalic vein stenosis. Of the remaining 3 patients, 2 had subclavian vein
      occlusion, and 1 had left brachiocephalic vein occlusion. RESULTS: All the stent
      placement procedures were technically successful, and there were no major
      complications. Follow-up ranged from 2 weeks to 29 months. The 1-, 3-, 6- and 12
      month primary stent patency rates were 92.8, 85.7, 50 and 14.3%, respectively.
      Repeat interventions, including percutaneous transluminal angioplasty and
      additional stent placement, were required in 9 patients. The 3-, 6-, 12-month,
      and 2-year assisted primary stent patency rates were 100, 88.8, 55.5 and 33.3%,
      respectively. CONCLUSION: Endovascular stent placement is an effective
      alternative to surgery in patients with shunt dysfunction due to obstruction of
      an upper extremity central vein. Repeated interventions are usually required to
      prolong stent patency.

PMID- 14975497
TI  - Clubbed fingers: the claws we lost?
AB  - Clubbed digits resemble the human embryonic fingers and toes, which look like the
      digits of a claw. Clubbed digits, thus, may represent the return of the embryonic
      claw and may even represent the claws man has lost during evolution, if
      ontogenesis really recapitulates phylogenesis. We put forward the hypothesis that
      secondary clubbing, like gynecomastia, is caused by a pathologic condition, which
      alters hormone levels in the blood, leading to the activation of 'dormant' genes,
      resulting in the development of an organ. However, the nature of the diseases
      that cause clubbing suggests that these hormones may actually be cytokines,
      acting as hormones. The nature of these cytokines is not known. They may be
      identified by comparing their blood levels or the combination of their blood
      levels to the presence or absence of clubbing, but also to the degree of clubbing
      and its disappearance after treatment of the primary disease.

PMID- 14975498
TI  - The potential pathogenetic link between peripheral immune activation and the
      central innate immune response in neuropsychiatric systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology.
      Neuropsychiatric disturbances unexplained by drugs or by other untoward
      manifestations of disease are present in up to one-half of SLE patients and have
      profound economic and social impact. In patients with neuropsychiatric SLE,
      structural lesions have been identified in the hippocampus and proinflammatory
      cytokines have been detected in the cerebrospinal fluid. Similarly, murine models
      of lupus, such as MRL-lpr/lpr mice display behavioral disturbances which map to
      the hippocampus and exhibit overexpression of proinflammatory cytokine genes in
      hippocampal homogenates. Neuropsychiatric SLE typically occurs in the presence of
      serologically and clinically active lupus. In animal models of SLE, such as MRL
      lpr/lpr, NZB, BXSB, and [NZB x NZW]F(1), uncontrolled autoreactivity in the
      periphery is accompanied by behavioral disturbances that are chronic and
      progressive. These observations suggest the hypothesis that central nervous
      system disease in SLE is driven by cross-talk between the peripheral immune
      system and the brain's innate immune system, which results in the inexorable
      activation of astrocytes, microglia, and/or neurons within the hippocampus. This
      leads to overproduction of brain cytokines, which induce the synthesis of pro
      oxidant molecules, such as eicosanoids and reactive oxygen species, with
      resultant tissue injury. The cascade becomes self-perpetuating and eventuates in
      neuronal death, which is followed by impaired cognition. A better understanding
      of the molecular events that operate in the pathogenesis of neuropsychiatric SLE
      may provide the basis for a more rational therapeutic approach to this
      incompletely understood disease.

PMID- 14975499
TI  - Mechanical immunology: every mechanical crushing of a cell in living organisms
      results in an immunological reaction.
AB  - Throughout a living organism, the cells are constantly exposed to mechanical
      stresses. Because of these stresses, cells are continually broken down into
      various organs and structures. Thus, internal components of the cell that do not
      appear in the serum or extracellular space under stress-free conditions are
      released. These components, according to the ideas described here, can lead to an
      immune reaction and a subsequent inflammatory reaction. For these reasons the
      organism attempts to prevent the destruction of cells and employs a variety of
      mechanisms to try and achieve this aim. Apoptosis, i.e. suicide by the damaged
      cell, is one such mechanism as is the work of phagocytes that appear in the most
      varied organs. Further protection for the cell consists in the separation of the
      spaces in which the destruction of cells takes place by means of membranes and
      basal membranes. A further conclusion, which follows from this concept, is the
      separation of the CD4 and CD8 T-cell receptor spectra. Whereas CD4 T receptors
      recognise extracellular antigens the CD8 T-cell receptors recognise intracellular
      antigens. Conversely, the body's own extracellular structures do not lead to a
      reaction via the CD4 cells, the corresponding T-cell populations are eliminated
      and the body's own intracytoplasmic structures do not lead to a reaction via the
      CD8 cells. Each of the reverse combinations between structures and cell
      populations should lead, however, to an immune system reaction.

PMID- 14975500
TI  - A new therapeutic approach for the treatment of sepsis.
AB  - Despite important advances in understanding its pathophysiology, therapy for
      septic shock remains largely symptomatic and supportive. Aiming to elevate the
      systemic arterial blood pressure by using vasoconstrictor manoeuvers are
      preferred without paying much attention to the ischaemia produced at the
      peripheral tissues. Since, these maneuvers proved no remarkable success in
      reducing the mortality up to date, we now propose a different perspective in this
      manuscript. Although it is not always easy to distinguish the different phases of
      septic shock, at least two fundamentally different phases can be distinguished,
      i.e. (i) hyperdynamic phase and (ii) hypodynamic phase mandating the adoption of
      vasodilative and vasoconstrictive interventions, consequently. Additionally,
      endothelium-derived vasodilator and vasoconstrictor substances such as nitric
      oxide and endothelin play key roles in systemic inflammatory response syndrome
      that lead to fatal multiple organ dysfunction. Therefore, we hypothesize that the
      inhibition of nitric oxide production during earlier phases of septic shock
      combined with the blockade of endothelin receptors at later stages appear
      feasible and a novel strategy for the therapy of septic shock.

PMID- 14975501
TI  - Hypothesis of interference to superinfection between bovine spastic paresis and
      bovine spongiform encephalopathy; suggestions for experimentation, theoretical
      and practical interest.
AB  - Sub-acute transmissible spongiform encephalopathies (TSEs) or prion diseases are
      diseases of little known etiology. The origin of these diseases would appear to
      be an abnormal protease-resistant prion protein (PrP(res)) which would be
      infectious by directly inducing its defective conformation to the normal native
      protein (PrP(C)). This hypothesis does not account for certain aspects of TSEs,
      such as interference to superinfection: in laboratory animals, inoculation by
      means of an attenuated strain with a long incubation period protects against
      later infection by a very virulent strain with a short incubation period. The
      hypothesis is put forward that there exists a possibility of interference to
      superinfection between neurodegenerative diseases of unknown origin, thought to
      be similar to TSEs, and a later infection by a TSE. The study of this
      interference between bovine spastic paresis (BSP) and bovine spongiform
      encephalopathy (BSE) could be used as a model for this hypothesis. BSP is a very
      rare disease among cattle, of unknown etiology; it is curable, in the very early
      stages, by using tryptophan and especially lithium, potentiated by copper and
      manganese. An etiology close to that of TSEs has been suggested on several
      occasions. If interference could be demonstrated between BSP and BSE, interesting
      data would be provided concerning the etiology, the pathogenesis and possibly the
      treatment and prevention of these diseases. Notably, such data could lead to the
      development of a treatment and a prevention with lithium and amino acids
      precursors of neuromediators (tryptophan, tyrosine, glutamic acid, etc.), as well
      as the developing of a vaccine to combat TSEs, especially BSE and scrapie.

PMID- 14975502
TI  - Hypothesis links emergence of chloroquine-resistant malaria and other
      intracellular pathogens and suggests a new strategy for treatment of diseases
      caused by intracellular parasites.
AB  - Chloroquine and related anti-malarial drugs appear to promote apoptosis in T
      cells by suppressing NF-kappa-B, which enhances the expression of anti-apoptotic
      proteins (e.g., Bcl-2). Thus, chloroquine has found applications in autoimmune
      diseases where it apparently facilitates apoptosis of abnormally persistent T
      cell clones. The mode of action of chloroquine in prevention of malaria is not
      known, but it may be to minimize replication of the parasite in the liver cells,
      which occurs before invasion of the erythrocytes, by facilitating premature
      apoptosis of the infected host cells. After introduction of chloroquine in the
      1950s world-wide for prophylactic use, chloroquine-resistant malaria emerged.
      Here it is hypothesized that concurrent with emergence of chloroquine-resistant
      malaria (presumably with enhanced anti-apoptotic capabilities), other
      intracellular parasites have evolved to enhance their ability to prevent
      apoptosis in host cells. Two examples of viral diseases that have emerged from
      areas of high incidence of chloroquine-resistant malaria are AIDS from HIV and
      SARS from coronavirus. The hypothesis holds that prophylactic exposure to pro
      apoptotic chloroquine drugs caused natural selection for strains of viruses and
      other parasites that have enhanced anti-apoptotic abilities. When transmitted to
      host organisms that are not under the influence of the pro-apoptotic drug, the
      new "anti-apoptotic" strains may cause unexpected diseases. In the case of SARS,
      the coronavirus appears to have accessed a new niche where it proves to be lethal
      to its host. In the case of AIDS, the HIV (which has had a long-term symbiotic
      relationship with primates) has run amuck because the infected cells are now
      substantially more tolerant to the toxins (i.e., resistant to apoptosis) that
      they secrete than the uninfected bystander cells, which are not unusually
      resistant to apoptosis. A corollary to the hypothesis is that if the level of
      resistance to apoptosis in the infected cells were no higher than the level of
      resistance in the bystander cells, then the infected cells would preferentially
      kill themselves through apoptosis. It appears that in the case of HIV, the
      increased resistance to apoptosis is provided by expression of Bcl-2 and
      suppression of p53. Hence, drugs that suppresses Bcl-2 or restore p53 function
      might be effective in restoring the parity of resistance to apoptosis between
      infected and uninfected cells. Currently, an antisense drug targeting Bcl-2
      (G3139/Genasense(TM), Genta, Inc.) is in late-stage cancer trials and may be on
      the market for those indications in months. It would be interesting to try these
      drugs against various intracellular parasites including HIV. This approach to
      prevent or eliminate active infections might be particularly attractive against a
      range of parasites (virus, bacteria, protozoa, fungus) when safe and effective
      vaccines are not available.

PMID- 14975503
TI  - Human immunodeficiency virus reservoir might be actively eradicated as residual
      malignant cells by cytotoxic chemotherapy.
AB  - A unique characteristic of human immunodeficiency virus (HIV) infection is that
      the virus must incorporate its cDNA into the host genomic DNA for replication.
      Once the virus gets into the host genome and becomes a part of the host genetic
      materials, elimination of the virus without killing the infected cells is
      virtually impossible. The use of highly active antiretroviral therapy (HAART) can
      result in a substantial decline in viremia. However, HAART does not eradicate
      HIV. The progressive HIV infection will unavoidably rebound after a cessation of
      the treatment. Searching for a new combination therapeutic strategy with
      cytotoxic agents that eliminate or significantly reduce the HIV reservoir is a
      potential way for better control of the disease. Theoretically, the HIV reservoir
      can be gradually eradicated by long-term use of certain antimetabolic cytotoxic
      drugs coupled with proper activation of latently infected cells, if viral
      replication is completely blocked by antiretroviral chemotherapy to protect
      uninfected, susceptible cells.

PMID- 14975504
TI  - How against HIV - using immunology or genetic engineering.
AB  - How against HIV - using Immunology or Genetic Engineering represents a thinking
      about the way how to overarch the HIV virus. Namely, by the combination of
      Immunological and the methods of Genetic Engineering, we could create a new
      nonreproducible virus which would be a competitor to real HIV for CD4 receptors.
      Competitors, by their affinity, would be acting in order to engage the CD4
      receptors, making them nonaccessible for real HIV. But, at the same time,
      competitors, by their size, would be just physically covering a small deal of CD4
      receptors. That way these free CD4 receptors would also be nonaccessible for real
      HIV, but accessible for immunomolecules, like, for an example MHC II is. That way
      the physiological role of CD4 receptors in immunological reactions, would be
      saved, and that fact would help us in our intention to expel the provirus
      integrated in its host CD4 lymphocite, by already known immunological mechanisms.
      Out of the host cell (CD4 Lymphocite) the HIV virus is very responsive for our
      Immune System and it would be destroyed.

PMID- 14975505
TI  - Bactericidal cationic peptides can also function as bacteriolysis-inducing agents
      mimicking beta-lactam antibiotics?; it is enigmatic why this concept is
      consistently disregarded.
AB  - Although there is a general consensus that highly cationic peptides kill bacteria
      primarily by injuring their membranes, an additional hypothesis is proposed
      suggesting that a large variety of cationic peptides might also render bacteria
      non viable by activating their autolytic wall enzymes - muramidases (a "Trojan
      Horse" phenomenon), resulting in bacteriolysis. This group of cationic peptides
      includes: lysozyme, lactoferrin, neutrophil-derived permeability increasing
      peptides, defensins, elastase, cathepsin G, and secretory phopholipase A2. In
      this respect, cationic peptides mimic the bactericidal/bacteriolytic effects
      exerted by of beta-lactam antibiotics. Bacteriolysis results in a massive release
      of the pro-inflammatory cell-wall components, endotoxin (LPS), lipoteichoic acid
      (LTA) and peptidoglycan (PPG), which if not effectively controlled, can trigger
      the coagulation and complement cascades, the release from phagocytes of
      inflammatory cytokines, reactive oxygen and nitrogen species, and proteinases.
      Synergism (a "cross-talk") among such agonists released following bacteriolysis,
      is probably the main cause for septic shock and multiple organ failure. It is
      proposed that a use of bacteriolysis-inducing antibiotics should be avoided in
      bacteremic patients and particularly in those patients already suspected of
      developing shock symptoms as these might further enhance bacteriolysis and the
      release of LPS, LTA and PPG. Furthermore, in additonal to the supportive regimen
      exercised in intensive care settings, a use of non bacteriolysis-inducing
      antibiotics when combined with highly sulfated compounds (e.g. heparin, and other
      clinically certified polysufates) should be considered instead, as these might
      prevent the activation of the microbial own autolytic systems induced either by
      highly cationic peptides released by activated phagocytes or by the highly
      bacteriolytic beta-lactams. Polysulfates might also depress the deleterious
      effects of the complement cascade and the use of combinations among anti-oxidants
      ( N-acetyl cysteine), proteinase inhibitors and phospholipids might prove
      effective to depress the synergistic cytotoxic effects induced by inflammatory
      agonists. Also, a use of gamma globulin enriched either in anti-LPS or in anti
      LTA activities might serve to prevent the binding of these toxins to receptors
      upon macrophage which upon activation generate inflammatory cytokines. Thus, a
      use of "cocktails" of anti-inflammatory agents might replace the unsuccessful use
      of single antagonists proven in scores of clinical trials of sepsis to by
      ineffective in prolonging the lives of patients. It is enigmatic why the concept,
      and the publications which support a role for cationic peptides also as potent
      inducers of bacteriolysis, an arch evil and a deleterious phenomenon which
      undoubtedly plays a pivotal role in the pathophysiology of post-infectious
      sequelae, has been consistently disregarded.

PMID- 14975506
TI  - Principles of magnetodynamic chemotherapy.
AB  - Basic principles of a novel method of cancer treatment are explained. Method is
      based on the thermal activation of an inactive prodrug encapsulated in
      magnetoliposomes via Neel and Brown effects of inductive heating of subdomain
      superparamagnetic particles to sufficiently high temperatures. This principle may
      be combined with targeted drug delivery (using constant magnetic field) and
      controlled release (using high-frequency magnetic field) of an activated drug
      entrapped in magnetoliposomes. Using this method drug may be applied very
      selectively in the particular site of organism and this procedure may be repeated
      several times using e.g. stealth magnetoliposomes which are circulating in a
      blood-stream for several days. Moreover the magnetoliposomes concentrated by
      external constant magnetic field in tumor vasculature may lead to embolic lesions
      and necrosis of a tumor body and further the heat produced for thermal activation
      of a drug enhances the effect of chemotherapy by local hyperthermic treatment of
      neoplastic cells.

PMID- 14975507
TI  - Induction of apoptosis as a proposed pathophysiological link between glaucoma and
      Helicobacter pylori infection.
AB  - Although apoptosis is equally important both for the development and for the
      maintenance of homeostasis in some adult tissues, it can also be associated with
      disease processes. Current studies indicate that apoptosis is a mechanism of cell
      death in several important ocular and gastrointestinal diseases including
      glaucoma, and Helicobacter pylori (H. pylori)-induced upper gastrointestinal
      disorders and/or extraintestinal diseases, including autoimmune and
      neurodegenerative ones (Sjogren's syndrome, Guillain-Barre syndrome or
      Parkinson's disease). Glaucoma is also associated with similar autoimmune and
      neurodegenerative disorders, characterized by apoptotic loss of specific
      populations of neurons. Recently, a high prevalence of H. pylori infection has
      been recognized in patients with chronic open-angle glaucoma. In addition, H.
      pylori eradication may positively influence glaucoma parameters, thereby
      suggesting a possible causal link between H. pylori and glaucoma. H. pylori
      infection may influence the pathophysiology of glaucoma by releasing various
      proinflammatory and vasoactive substances, as well as by influencing apoptotic
      process; parameters that may also exert their own effects in the induction and/or
      progression of glaucomatous neuropathy. Importantly, H. pylori infection and
      glaucoma share the Fas/FasL and the mitochondria-mediated apoptotic pathways,
      thereby proposing an apoptotic link in the pathophysiology of both diseases.

PMID- 14975508
TI  - Recommendation of modified classification for odontogenic carcinomas.
AB  - Primary squamous cell carcinoma (SCC) derived from odontogenic epithelium is
      diagnosed as primary intraosseous carcinoma (PIOC). The term "intraosseous" means
      the bone marrow spaces. Odontogenic cells, however, exist not only in the bone
      marrow space but also in the periodontal space and the subepithelial soft tissue
      space. In our survey for 36 SCC lesions of odontogenic origin, many lesions
      involved two or all of the three spaces. There was only one lesion which involved
      the bone marrow space alone. In some cases, the extent of the early lesions was
      restricted around the tooth or at a part of the alveolar crest. The possibility
      of a SCC of odontogenic origin arising in the periodontal and the subepithelial
      soft tissue spaces was suggested. We proposed the term "Odontogenic SCC" to
      replace "PIOC".

PMID- 14975509
TI  - EBV-associated neoplasms: alternative pathogenetic pathways.
AB  - We propose that there are two main classes of Epstein-Barr virus (EBV) associated
      lymphomas: primarily malignant Burkitt's Lymphoma (BL) and Hodgkin's Disease
      (HD), on one hand, and primarily benign lymphoproliferations, e.g., post
      transplant lymphoproliferative disease (PTLD) on the other hand. PTLD may start
      as a benign lymphoproliferation which becomes malignant if out of T cell control
      for too long. Our discovery of a binding site for the oncoprotein c-Myc at a
      central position of the EBV genome favours a distinction of pathogenetic pathways
      or scenarios for the proposed lymphoma classes. In the first scenario nuclear
      maintenance of the EBV genome and activation of viral anti-apoptotic functions
      with the help of c-Myc are indispensable for the origin of malignant tumours (BL,
      HD) from the germinal centre B-cell. In the second scenario expression of the
      main viral transforming protein EBNA2 is essential for immortalisation and non
      malignant morphological transformation of any (germinal centre derived or non
      germinal centre) B-cell in the absence of T cell control. Although EBNA2
      expression is permissible, under specific circumstances, in malignant B-cells, it
      is not required for oncogenesis.

PMID- 14975510
TI  - A new proposal for the mechanism of glycine hydroxylation as catalyzed by
      peptidylglycine alpha-hydroxylating monooxygenase (PHM).
AB  - The title enzyme, peptidylglycine alpha-hydroxylating monooxygenase (PHM), is
      essential to the in vivo generation of a wide variety of physiologically
      significant alpha-amidated peptide hormones from the corresponding C-terminal
      glycine-extended prohormones. Over a 20-year period of time a massive amount of
      experimental information about the enzyme has accumulated, but its mechanism of
      action has remained obscure. A major stumbling block to proposed mechanisms is
      the fact that the two copper atoms found in the active site are fixed 11 A apart.
      A novel mechanism is now proposed which accommodates and, indeed, requires this
      separation and proceeds through energetically accessible steps. It is proposed
      that hydroxylation at the terminal glycine residue of the C-terminal glycine
      extended prohormone proceeds first by a concerted sequence of single-electron
      electromeric shifts, whereby both copper atoms are oxidized to Cu(II), oxygen is
      reduced to peroxide coordinated to Cu(M), and the glycyl group is tautomerized to
      its enolate coordinately bound to Cu(H). Upon subsequent reversion to the
      carbonyl tautomer, by a sequence of two-electron shifts, the enolate as
      nucleophile reacts with peroxide as electrophile, generating product alpha
      hydroxyglycine, decoordinated from Cu(H), reopening the mouth of the active-site
      pocket to egress of product and ingress of substrates.

PMID- 14975511
TI  - Slower and incomplete retrieval of speech motor plans is the proximal source of
      stuttering: stutters occur when syllable motor plans stored in memory are
      concatenated to produce the utterance motor plan.
AB  - This paper describes a hypothesis about stuttering that distinguishes between two
      methods of assembling the speech motor plan for an utterance - speech
      construction, which involves real-time preparation of the speech motor plan and
      speech concatenation, which involves retrieval and chaining of syllable motor
      plans stored in memory. It is hypothesized that stutters are significantly
      reduced when people who stutter (PWS) speak in novel speaking patterns such as
      whispering and prolonged speech because these unaccustomed speaking tasks require
      speech construction. In contrast, when PWS speak in their habitual speech
      pattern, concatenating syllable motor plans stored in memory, they stutter.
      Reaction time studies and the effect of word frequency on stutter rate show that
      PWS are slower in retrieving stored motor plans during speech concatenation. On
      the other hand, conditions that positively prime the retrieval of motor plans -
      phonological priming, reading, production of serial speech, speech shadowing, and
      stuttering adaptation tasks - speed up the retrieval of motor plans and,
      therefore, reduce the amount of stutters. The slower retrieval of syllable motor
      plans may lead to an incomplete specification of the utterance motor plan.
      Stutters result when the articulatory system attempts to execute an
      underspecified utterance motor plan.

PMID- 14975512
TI  - The "Yoking" of glutamatergic brain mechanisms involved in controlling brain
      neuronal excitability and psychosis to brain mechanisms involved in appetite
      regulation: a new hypothesis on the origin of psychosis.
AB  - The authors speculate that the human primate evolved psychosis generating brain
      mechanisms in the service of certain feeding behaviors (i.e., appetite, foraging)
      during the course of evolution. Furthermore, these "psychosis generating brain
      mechanisms" may have grown directly out of brain mechanisms servicing appetite,
      of which neuropeptide Y (NPY) played an important role. A case is made for an NPY
      contribution to the pathophysiology of psychosis. We hypothesize that the
      psychomimetic effects of NPY extend to supporting certain "psychomotor" functions
      that might have been useful for obtaining food resources in "stressful
      environments" (potentially food resource rich/predator-competitor dangerous). The
      "psychomotor" functions proposed include helping the evolving ancestral human
      primate overcome behavioral inhibitions and fears related to venturing into
      "stressful environments" (potentially food resource rich/predator-competitor
      dangerous) after their home ranges had been stripped of resources, by providing
      feelings of decreased anxiety (anxiolysis), infatigability, and, perhaps, even
      grandiose delusions of physical ability and supernatural supports. We further
      speculate that it is this NPY mechanism that in part becomes dysregulated in
      idiopathic psychotic disorders such as schizophrenia. The NPY connection with
      psychosis could theoretically account for the possible associations between
      weight changes and antipsychotic response (e.g. [Acta Psychiatr. Scand. 100
      (1999) 3] reported by others and body mass index and cocaine-induced psychosis by
      our group (i.e. [Israel J. Psychiatr. (2004), in submission]).

PMID- 14975513
TI  - Depression as a communicable disorder.
AB  - 'Communicable disorder' can be defined as a disorder capable of being transmitted
      in the form of negative emotion(s) from living or non-living being(s) to
      susceptible host. Thus, communicable disorder is transmitted from the source or
      reservoir of disorder to the susceptible host. The source of disorder can be
      defined as the living or non-living being from which the disorder in the form of
      negative emotion(s) gets transmitted to the susceptible host. The reservoir of
      disorder can be defined as the living or non-living being in which the negative
      emotion(s) lives, on which it depends primarily for survival, and where it
      preserves and reproduces itself in such a manner that it can be transmitted to
      the susceptible host. Depression is a disorder and can be transmitted in the form
      of negative emotion(s) and therefore can be considered to fall under the category
      of communicable disorder. The detection and depression of the source and
      reservoir of depression can not only help in its diagnosis and treatment but can
      also prevent its spread. The paper proposes a study to help calculate the
      percentage susceptibility of an individual to depression and a means to treat
      depression by depressing the source and reservoir of depression. The paper also
      proposes a new word, Emotional immunization and defines it as that as that
      positive activity of emotion(s), which leads to its stabilization when, subjected
      to negative emotion(s).

PMID- 14975514
TI  - Schizophrenia and cancer: the adrenochrome balanced morphism.
AB  - Cancer might be expected to be more common amongst schizophrenics than the
      general population. They frequently live in selenium deficient regions, have
      seriously compromised antioxidant defense systems and chain-smoke. The available
      literature on the cancer-schizoprenia relationship in patients from England,
      Wales, Ireland, Denmark, USA and Japan, however, strongly suggests that the
      reverse is true. One of the authors (Hoffer) has treated 4000 schizophrenics
      since 1952. Only four of these patients has developed cancer. Since low cancer
      incidence has been recorded amongst patients treated by both conventional
      physicians using pharmaceuticals and by orthomolecular doctors who emphasize
      vitamins and minerals, it follows that this depressed cancer incidence must be
      related to the biochemistry of the disorder itself. Taken as a whole, therefore,
      the evidence seems to suggest that schizophrenics, their siblings and parents are
      less susceptible to cancer than the general population. These relationships seem
      compatible with one or more genetic risk factors for schizophrenia that offer(s)
      a selective advantage against cancer. There is experimental evidence that appears
      to support this possibility. Matrix Pharmaceuticals Inc. has received a US patent
      covering the composition of IntraDose Injectable Gel. This gel contains cisplatin
      and epinephrine (adrenaline) and is designed to be injected directly into tumour
      masses. Cisplatin is a very powerful oxidant which will almost certainly rapidly
      convert the adrenaline to adrenochrome. While the manufacturers of IntraDose
      consider cisplatin to be the active cytotoxic agent in IntraDose, it seems more
      likely that adrenochrome and its derivatives may, in fact, be more effective.
      IntraDose gel has undergone or is undergoing a series of Phase III open-label
      clinical studies, being injected into patients' tumours that have been identified
      as the most troublesome by their physicians. The results have been impressive for
      breast cancer, malignant melanoma, esophageal cancer and cancer of the head, neck
      and liver. The evidence suggests that there are balanced morphisms in
      schizophrenia that result in above normal exposure to catecholamine derivatives.
      Since such catecholamines are both hallucinogenic and anticarcinogenic abnormally
      high exposure to them simultaneously increases susceptibility to schizophrenia
      and reduces the probability of developing cancer. These observations have
      significant implications for the treatment of both illnesses.

PMID- 14975515
TI  - Stress and dopamine: implications for the pathophysiology of chronic widespread
      pain.
AB  - Fibromyalgia has been called a "stress-related disorder" due to the onset and
      exacerbation of symptoms in the context of stressful events. Evidence suggests
      that inhibition of tonic pain is mediated by activation of mesolimbic dopamine
      neurons, arising from the cell bodies of the ventral tegmental area and
      projecting to the nucleus accumbens. This pain-suppression system is activated by
      acute stress, via the release of endogenous opioids and substance P within the
      ventral tegmental area. However, prolonged exposure to unavoidable stress
      produces both reduction of dopamine output in the nucleus accumbens and
      development of persistent hyperalgesia. It is proposed that a stress-related
      reduction of dopaminergic tone within the nucleus accumbens contributes to the
      development of hyperalgesia in the context of chronic stress and thus plays a
      role in the pathogenesis of fibromyalgia. A stress-related dysfunction of
      mesolimbic dopaminergic activity might serve as the basis for other fibromyalgia
      associated phenomena as well.

PMID- 14975516
TI  - Time to reevaluate the therapeutic use of calcitonin and biological role
      attributable to parafollicular (C) cells.
AB  - There is rich anecdotal evidence that calcitonin significantly increases bone
      mineral density and reduces fracture risk. However, observation in a previous
      study of an increased bone formation in calcitonin-deficient mice has led us to
      reevaluate the therapeutic use of calcitonin and to investigate the primary role
      of parafollicular (C) cells of the thyroid gland. We found that C cells are
      involved mainly in the regulation of follicular cell activity in a paracrine
      manner and in doing so they may regulate the growth rate in newborn by affecting
      the thyroid hormone levels in the early postnatal period. In the light of reports
      that showed thyroid physiology is different between populations and it is
      affected by environmental factors we suggested that C cells may be involved in
      population differences in thyroid physiology and environmental adaptation. We
      conclude that C cells may facilitate the adaptation of the follicular cells to
      environmental changes, enabling more effective coordinated functions of the body
      and producing variations between populations.

PMID- 14975517
TI  - Anti-thyroid thioureylenes in the treatment of psoriasis.
AB  - Psoriasis is a common skin disorder associated with significant morbidity. Many
      agents are used in the medical management of this debilitating condition with the
      newer anti-cytokine agents being the most recent addition to the pharmacological
      armamentarium to battle the disorder. Cost concerns are very important with the
      newer "biologic" treatments costing in excess of 10,000 US dollars annually. The
      need for cheaper, orally administered agents is therefore imperative. This paper
      addresses the potential role of anti-thyroid thioureylenes, propylthiouracil and
      methimazole, in the treatment of psoriasis and reviews the possible mechanism of
      action of these drugs in this disorder. It is hypothesized that the beneficial
      effect of anti-thyroid thioureylenes in psoriasis is linked to their effect as
      anti-proliferative agents as reflected by significant decrease in markers of
      cellular proliferation such as proliferative cell nuclear antigen in biopsy
      specimens after treatment with these drugs. Propylthiouracil has been shown to
      bind to the hepatic T 3 receptor and it is possible that propylthiouracil (6-n
      propyl-2-thiouracil) binding to the ligand-binding site normally occupied by T 3
      impairs transcription by inactivating the effect of T 3 as well as by squelching
      retinoic X receptor heterodimer formation with other receptors of the steroid
      receptor superfamily such as the peroxisome proliferator-activated receptor,
      retinoic acid receptor and vitamin D receptors.

PMID- 14975518
TI  - Is androgenic alopecia a result of endocrine effects on the vasculature?
AB  - Androgenic alopecia is a condition of concern for many patients. Though much has
      been learned about this condition, the exact pathophysiological mechanism is yet
      to be established. Currently most study concerning androgenic alopecia has
      focused on the effects of androgens on the pilosebaceous unit itself. An area of
      study that has received considerably less attention is that of androgens inducing
      baldness by indirect effects, that is, effects on tissues other than the
      pilosebaceous unit. In this paper, the author offers a novel hypothesis in which
      androgenic hair loss is mediated via the effects of androgens on the vasculature
      supplying the scalp. In this new hypothesis androgens effect anatomical changes
      in the vasculature of susceptible individuals, resulting in an environment in
      which hair growth is hindered and eventually ceases. The author discusses past
      studies demonstrating the effects of androgens on vessels and how these effects
      may relate to anatomical changes in the vasculature leading to hair loss. Also
      included is a discussion on future experimentation to test this new hypothesis.

PMID- 14975519
TI  - Serum markers of stored body iron are not appropriate markers of health effects
      of iron: a focus on serum ferritin.
AB  - Experimental studies have consistently shown that iron is a critical catalyst in
      generating oxygen free radicals via Fenton chemistry. Nevertheless, epidemiologic
      studies conflict on the association between stored body iron markers and disease
      outcomes, including coronary heart disease. We hypothesize that stored body iron
      markers common in epidemiologic studies, such as serum ferritin, transferrin
      saturation, iron, or iron-binding capacity, are inappropriate to investigate
      harmful health effects related to iron overload. Oxygen free radicals are
      produced only by free iron, but stored body iron markers reflect iron bound to
      ferritin or transferrin, which are produced to sequester catalytically active
      free iron. Moreover, increased serum ferritin may occur as a defense mechanism in
      response to oxidative stress; such increase might eventually minimize oxidative
      stress and consequent pathology due to free iron. Therefore, though highly
      correlated with stored body iron, a measure of bound iron will fail to identify
      any harmful effect, unless it is also a marker of free iron. It is generally
      believed that free iron rarely exists, except in iron-overload with 100%
      transferrin saturation. However, some recent studies find non-transferrin bound
      iron (NTBI) or the intracellular labile iron pool (LIP) in the presence of
      triggers disturbing iron homeostasis, such as alcohol consumption. In contrast to
      the tight bond in ferritin or transferrin, free iron is more likely to dissociate
      from a looser bond. Therefore research on the relation of iron with disease
      outcomes should investigate NTBI or the intracellular LIP. Any positive influence
      of iron on coronary heart and other diseases might be observable only when a
      trigger is present. These factors may explain why there have been conflicting
      results between serum markers of stored body iron and disease outcomes in
      epidemiological studies.

PMID- 14975520
TI  - Paroxetine for hepatopulmonary syndrome?
AB  - Hepatopulmonary syndrome (HPS) is a severe pulmonary sequela which can affect up
      to 15% of patients with cirrhotic liver disease. There is no treatment for HPS
      other than liver transplantation. The cause of HPS is incompletely understood,
      but the pulmonary vasodilation in HPS is thought to be related to increased
      levels of nitric oxide. We therefore suggest that, the extremely safe and
      commonly used antidepressant medication paroxetine (Paxil) which is a potent
      nitric oxide synthase (NOS) inhibitor be considered for use in HPS.

PMID- 14975521
TI  - Pathophysiological aspects of bladder dysfunction: a new hypothesis for the
      prevention of 'prostatic' symptoms.
AB  - This article reviews the literature on the pathophysiology of male lower urinary
      tract symptoms (LUTS) with the intention of developing a new preventive
      intervention for this bothersome disease. Traditionally, male voiding dysfunction
      has been thought to arise from bladder outlet obstruction (BOO) caused by
      prostatic enlargement. Many years of research, however, have shown that a clear
      relationship between the size of the prostate and the occurrence or severity of
      symptoms is doubtful. Because of its crucial role in urination, it is
      increasingly being accepted that the clinical manifestation of voiding
      dysfunction relies on the functional behaviour of the bladder. Several animal
      studies have shown that bladder performance can be improved by increasing urine
      output. Contrary to alterations observed in pathologic situations, an increased
      urine output provides a physiologic stimulus for animal bladder function
      improvement. We hypothesise that a trained bladder should be less susceptible to
      the harmful effects of ageing and obstruction. Future symptoms may thus be
      prevented. In humans an increased urine output can be achieved by drinking
      additional water, which could be an adequate preventive intervention.

PMID- 14975522
TI  - Pathogenesis of spontaneous cervico-cerebral artery dissection. A hypothesis and
      a review of the literature.
AB  - The pathogenesis of spontaneous cervico-cerebral artery dissection remains
      speculative due to the rarity of histopathological observations, which often
      correspond to late stage lesions. Transposition of theoretic data from
      experimental models, study of pathologies with morphological lesions of the same
      type, and review of some clinical cases, suggest a sequence for the pathological
      events leading to arterial dissection. Arterial dysplasia, aneurysms and
      dissections could all result from vascular remodeling in response to endothelial
      injury. It induces morphologic changes of the internal elastic lamina, smooth
      muscle cell proliferation, various matrix abnormalities involving the fibrillary
      components or their enzymatic regulation, arterial wall neoangiogenesis and
      dissection. Endothelial dysfunction could so play a key role in the imbalance
      between arterial degenerative and reparative processes and the initiation of
      cervico-cerebral artery dissection.

PMID- 14975523
TI  - Are living beings in the state of self-organized criticality? A new
      interpretation of data on work incapacity due to low back pain.
AB  - Using data published elsewhere I demonstrate in this paper that the frequency
      distribution of the duration of work incapacity from low back pain follows a
      power law. Power laws are not common in medicine and the question arises why we
      can find one here. The peculiarity of the data considered here is that they
      embrace not only the passive reaction but also the whole spectrum of possible
      active responses of a living being to a disturbance. For the duration of sick
      leave due to low back pain is not only influenced by the defect a person is
      affected by, but even more dependent on how he or she copes with it. Coping
      comprises a broad range of possibilities from denial of the disability to its
      aggravation, from therapy to malingering. In contrast to the scientific ideal
      none of these faculties has been excluded in the data used here. They concern the
      whole living being. Power laws are typical for systems in the state of self
      organized criticality. The system involved in the case of low back pain is the
      whole living human being with all its possibilities to react and to respond.
      Thus, my findings support empirically the hypothesis that living beings are in
      the state of self-organized criticality.

PMID- 14975524
TI  - Is acne really a disease?: a theory of acne as an evolutionarily significant,
      high-order psychoneuroimmune interaction timed to cortical development with a
      crucial role in mate choice.
AB  - Adolescent acne is considered from the perspective of evolutionary psychology
      with an emphasis on a role in mate choice. The fact that acne, which is almost
      universal and not a true infection, is (1) initiated at puberty by the action of
      pubertal hormones on likely distinct, pro-acne follices, and (2) typically
      resolves in one's early twenties when prefrontal cortex development is complete,
      suggests that the condition's timeframe is meaningful. Acne's conspicuous
      localization on the face, and its ability to elicit reflexive disgust and
      avoidance in observers, suggests a possible role in sexual selection. The
      pathophysiology of acne is reviewed, and the suggestion made that, far from being
      a disease, adolescent acne is a normal physiological process - a high-order
      psychoneuroimmune interaction - that functions to ward off potential mates until
      the afflicted individual is some years past the age of reproductive maturity, and
      thus emotionally, intellectually, and physically fit to be a parent.

PMID- 14975527
TI  - Translocation of proteins across archaeal cytoplasmic membranes.
AB  - All cells need to transport proteins across hydrophobic membranes. Several
      mechanisms have evolved to facilitate this transport, including: (i) the
      universally-conserved Sec system, which transports proteins in an unfolded
      conformation and is thought to be the major translocation pathway in most
      organisms and (ii) the Tat system, which transports proteins that have already
      obtained some degree of tertiary structure. Here, we present the current
      understanding of these processes in the domain Archaea, and how they compare to
      the corresponding pathways in bacteria and eukaryotes.

PMID- 14975528
TI  - Some like it cold: biocatalysis at low temperatures.
AB  - In the last few years, increased attention has been focused on a class of
      organisms called psychrophiles. These organisms, hosts of permanently cold
      habitats, often display metabolic fluxes more or less comparable to those
      exhibited by mesophilic organisms at moderate temperatures. Psychrophiles have
      evolved by producing, among other peculiarities, "cold-adapted" enzymes which
      have the properties to cope with the reduction of chemical reaction rates induced
      by low temperatures. Thermal compensation in these enzymes is reached, in most
      cases, through a high catalytic efficiency associated, however, with a low
      thermal stability. Thanks to recent advances provided by X-ray crystallography,
      structure modelling, protein engineering and biophysical studies, the adaptation
      strategies are beginning to be understood. The emerging picture suggests that
      psychrophilic enzymes are characterized by an improved flexibility of the
      structural components involved in the catalytic cycle, whereas other protein
      regions, if not implicated in catalysis, may be even more rigid than their
      mesophilic counterparts. Due to their attractive properties, i.e., a high
      specific activity and a low thermal stability, these enzymes constitute a
      tremendous potential for fundamental research and biotechnological applications.

PMID- 14975529
TI  - Shigella flexneri infection: pathogenesis and vaccine development.
AB  - Shigella flexneri is a gram-negative bacterium which causes the most communicable
      of bacterial dysenteries, shigellosis. Shigellosis causes 1.1 million deaths and
      over 164 million cases each year, with the majority of cases occurring in the
      children of developing nations. The pathogenesis of S. flexneri is based on the
      bacteria's ability to invade and replicate within the colonic epithelium, which
      results in severe inflammation and epithelial destruction. The molecular
      mechanisms used by S. flexneri to cross the epithelial barrier, evade the host's
      immune response and enter epithelial cells have been studied extensively in both
      in vitro and in vivo models. Consequently, numerous virulence factors essential
      to bacterial invasion, intercellular spread and the induction of inflammation
      have been identified in S. flexneri. The inflammation produced by the host has
      been implicated in both the destruction of the colonic epithelium and in
      controlling and containing the Shigella infection. The host's humoral response to
      S. flexneri also appears to be important in protecting the host, whilst the role
      of the cellular immune response remains unclear. The host's immune response to
      shigellosis is serotype-specific and protective against reinfection by the same
      serotype, making vaccination a possibility. Since the 1940s vaccines for S.
      flexneri have been developed with little success, however, the growing
      understanding of S. flexneri's pathogenesis and the host's immune response is
      assisting in the generation of more refined vaccine strategies. Current research
      encompasses a variety of vaccine types, which despite disparity in their efficacy
      and safety in humans represent promising progress in S. flexneri vaccine
      development.

PMID- 14975530
TI  - Oncomodulatory signals by regulatory proteins encoded by human cytomegalovirus: a
      novel role for viral infection in tumor progression.
AB  - A high frequency of human cytomegalovirus (HCMV) genome and antigens in tumor
      samples of patients with different malignancies is now well documented, although
      the causative role for HCMV in the development of the neoplasias remains to be
      established. HCMV infection can modulate multiple cellular regulatory and
      signalling pathways in a manner similar to that of oncoproteins of small DNA
      tumor viruses such as human papilloma virus or adenoviruses. However, in contrast
      to these DNA tumor viruses, HCMV infection fails to transform susceptible normal
      human cells. There is now growing evidence that tumor cells with disrupted
      regulatory and signalling pathways enable HCMV to modulate their properties
      including stimulation of cell proliferation, survival, invasion, production of
      angiogenic factors, and immunogenic properties. In contrast to previously
      suggested "hit and run" transformation we suggest that persistence in tumor cells
      is essential for HCMV to fully express its oncomodulatory effects. These effects
      are observed particularly in persistent HCMV infection and are mediated mainly by
      activity of HCMV regulatory proteins. In persistently HCMV-infected tumor cell
      lines - a selection of novel, slowly growing virus variants with changes in
      coding sequences for virus regulatory proteins takes place. As a result,
      oncomodulatory effects of HCMV infection may lead to a shift to more malignant
      phenotype of tumor cells contributing to tumor progression.

PMID- 14975531
TI  - A classification scheme for mobilization regions of bacterial plasmids.
AB  - Transmissible plasmids can be classified according to their mobilization ability,
      as being conjugative (self-transmissible) or mobilizable (transmissible only in
      the presence of additional conjugative functions). Naturally occurring
      mobilizable plasmids carry the genetic information necessary for relaxosome
      formation and processing, but lack the functions required for mating pair
      formation. Mobilizable plasmids have a tremendous impact in horizontal gene
      transfer in nature, including the spread of antibiotic resistance. However,
      analysis of their promiscuity and diversity has attracted less attention than
      that of conjugative plasmids. This review will focus on the analysis of the
      diversity of mobilizable plasmids. For this purpose, we primarily compared the
      amino acid sequences of their relaxases and, when pertinent, we compared these
      enzymes with conjugative plasmid relaxases. In this way, we established
      phylogenetic relationships among the members of each superfamily. We conducted a
      database and literature analysis that led us to propose a classification system
      for small mobilizable plasmids in families and superfamilies according to their
      mobilization regions. This review outlines the genetic organization of each
      family of mobilization regions, as well as the most relevant properties and
      relationships among their constituent encoded proteins. In this respect, the
      present review constitutes a first approach to the characterization of the global
      gene pool of mobilization regions of small mobilizable plasmids.

PMID- 14975532
TI  - Exploiting the potential of insects for in vivo pathogenicity testing of
      microbial pathogens.
AB  - Conventional assays for quantifying the virulence of microbial pathogens and
      mutants have traditionally relied upon the use of a range of mammalian species. A
      number of workers have demonstrated that insects can be used for evaluating
      microbial pathogenicity and provide results comparable to those that can be
      obtained with mammals since one component of the vertebrate immune system, the
      innate immune response, remains similar to that found in insects. Larvae of the
      Greater Wax Moth Galleria mellonella have been used to evaluate the virulence of
      a range of bacterial and fungal pathogens and a correlation with the virulence of
      these microbes in mice has been established. This review highlights the
      similarities of the vertebrate and insect innate immune responses to infection
      and identifies the potential use of insects for the in vivo evaluation of the
      microbial pathogenicity.

PMID- 14975533
TI  - Ecological role of energy taxis in microorganisms.
AB  - Motile microorganisms rapidly respond to changes in various physico-chemical
      gradients by directing their motility to more favorable surroundings. Energy
      generation is one of the most important parameters for the survival of
      microorganisms in their environment. Therefore it is not surprising that
      microorganisms are able to monitor changes in the cellular energy generating
      processes. The signal for this behavioral response, which is called energy taxis,
      originates within the electron transport system. By coupling energy metabolism
      and behavior, energy taxis is fine-tuned to the environment a cell finds itself
      in and allows efficient adaptation to changing conditions that affect cellular
      energy levels. Thus, energy taxis provides cells with a versatile sensory system
      that enables them to navigate to niches where energy generation is optimized.
      This behavior is likely to govern vertical species stratification and the active
      migration of motile cells in response to shifting gradients of electron donors
      and/or acceptors which are observed within microbial mats, sediments and soil
      pores. Energy taxis has been characterized in several species and might be
      widespread in the microbial world. Genome sequencing revealed that many
      microorganisms from aquatic and soil environments possess large numbers of
      chemoreceptors and are likely to be capable of energy taxis. In contrast, species
      that have a fewer number of chemoreceptors are often found in specific, confined
      environments, where relatively constant environmental conditions are expected.
      Future studies focusing on characterizing behavioral responses in species that
      are adapted to diverse environmental conditions should unravel the molecular
      mechanisms underlying sensory behavior in general and energy taxis in particular.
      Such knowledge is critical to a better understanding of the ecological role of
      energy taxis.

PMID- 14975534
TI  - Cardiac resynchronisation may reduce all-cause mortality: meta-analysis of
      preliminary COMPANION data with CONTAK-CD, InSync ICD, MIRACLE and MUSTIC.
AB  - Landmark trials have demonstrated that biventricular pacing (also called cardiac
      resynchronisation therapy or CRT) in chronic heart failure due to left
      ventricular dysfunction improves symptomatic status, exercise capacity and
      quality of life. Yet critically, all-cause mortality has not been demonstrated to
      be reduced in any of the four randomised controlled trials with mortality data
      (CONTAK-CD, InSync implantable-cardioverter defibrillator (ICD), MIRACLE and
      MUSTIC). With the much larger COMPANION study now terminated, however, the
      currently available pooled data from all five trials shows a significant
      reduction in all-cause mortality, odds ratio (OR), 0.74: 95% confidence interval
      (CI) 0.56-0.97. This may now establish biventricular pacing as a standard therapy
      for a specific subset of patients with chronic heart failure and LBBB.

PMID- 14975535
TI  - Meta-analyses of mortality and morbidity effects of an angiotensin receptor
      blocker in patients with chronic heart failure already receiving an ACE inhibitor
      (alone or with a beta-blocker).
AB  - BACKGROUND: While treatment with either angiotensin-converting enzyme inhibitors
      (ACEi) and angiotensin receptor blockers (ARBs) is clearly superior to placebo in
      the treatment of heart failure patients, controversy still surrounds the effects
      of ARBs in patients already receiving an ACEi. Even more controversial is the
      wisdom of administering ARBs in patients already on an ACEi and beta-blocker.
      METHODS: We present meta-analyses of the available randomised controlled trials
      to date (October 2003) of angiotensin II receptor antagonists versus placebo in
      patients with symptomatic chronic heart failure in which both groups received
      ACEi. The two largest eligible trials were CHARM-Added and Val-HeFT. We examined
      two endpoints: mortality and a combined endpoint of mortality and morbidity.
      RESULTS: In the first meta-analysis, covering all patients regardless of beta
      blocker use, we found a significant reduction in the combined endpoint (odds
      ratio [OR]=0.89; 95% confidence interval [CI] 0.81-0.98), but no significant
      reduction in mortality itself (OR=0.97; CI: 0.87-1.08). In the second meta
      analysis, covering patients concomitantly on beta-blockers, we found no
      significant effect on mortality (OR=1.08; CI: 0.90-1.29) or on the combined
      endpoint (OR=0.94; CI: 0.82-1.10). In the third meta-analysis, covering patients
      not on concomitant beta-blockers, there is clear evidence of a reduction in the
      combined endpoint (OR=0.83; CI: 0.73-0.94), but not on mortality (OR=0.93; CI:
      0.81-1.06). CONCLUSION: There is now good evidence for the use of ARBs to prevent
      events in patients with heart failure on ACEi who are not suitable for beta
      blockers.

PMID- 14975536
TI  - A rapid troponin I assay is not optimal for determination of troponin status and
      prediction of subsequent cardiac events at suspicion of unstable coronary
      syndromes.
AB  - BACKGROUND: Troponin is a specific marker of myocardial damage. For early
      prediction of coronary events in patients with suspicion of acute coronary
      syndromes the assay also needs to be highly sensitive. METHODS AND RESULTS: A
      rapid troponin I assay was performed prior to inclusion in 4447 acute coronary
      syndrome patients in the GUSTO-IV trial. A quantitative troponin T analysis was
      later performed on blood samples obtained at randomization by a central
      laboratory. There was an agreement between the rapid troponin I assay and
      troponin T (< or =/>0.1 microg/l) in 3596 (80.9%) patients. A positive rapid
      troponin I was identifying any elevation of troponin T (>0.01 microg/l) in 1990
      patients (90.4%) whereas a negative rapid troponin I was corresponding to
      negative troponin T (< or =0.01 microg/l) in only 1217 patients (54.2%). Patients
      with a positive versus negative rapid troponin I had an increased risk of death
      or myocardial infarction at 30 days (9.3 vs. 5.9%; odds ratio, O.R. 1.64; 95%
      confidence interval, 1.31-2.06). Troponin T elevation (>0.1 microg/l) provided a
      better (10.5 v. 4.9%, O.R. 2.26; C.I. 1.79-2.85) risk stratification. Regardless
      of a positive or a negative rapid troponin I, the troponin T result (>0.1 vs. <
      or =0.1 microg/l) stratified the patients into high and low risk of events at 30
      days, (10.3 vs. 5.7%, P=0.002) and (11.5 vs. 4.8%, P<0.001), respectively.
      CONCLUSION: In a population with non-ST elevation acute coronary syndrome a
      positive rapid troponin I assay is a specific indicator of troponin elevation and
      a predictor of early outcome. However, a negative rapid troponin I is not a
      reliable indicator of the absence of myocardial damage and does not indicate a
      low risk of subsequent cardiac events. A rapid troponin I assay was performed
      prior to inclusion in 4447 acute coronary syndrome patients in the GUSTO-IV trial
      and related to a centrally analyzed quantitative troponin T test. A positive
      rapid troponin I was well corresponding to any elevation of troponin T (>0.01
      microg/l) and predicted an unfavorable outcome at 30 days. However, a negative
      rapid troponin I was corresponding to troponin T < or =0.01 microg/l in only half
      of the patients. Troponin T >0.1 microg/l vs. < or =0.1 microg/l provided a
      better risk stratification than the rapid troponin I result. For patients with
      troponin T elevation (>0.1 microg/l) the 30 day event rate was high regardless of
      the rapid troponin I result.

PMID- 14975537
TI  - Effect of exercise on natriuretic peptides in plasma and urine in chronic heart
      failure.
AB  - BACKGROUND: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide
      (BNP) are elevated in chronic heart failure (CHF). ANP is known to be increased
      during exercise in healthy subjects and CHF, while the response in BNP during
      exercise is less clear and does not exist in C-type natriuretic peptide (CNP) and
      aquaporin-2 (AQP2) in either healthy subjects or CHF. METHODS: Eleven patients
      with CHF and eleven healthy subjects performed a maximal aerobic exercise test.
      ANP and BNP in plasma were determined every 3 min and at maximum exercise by
      radioimmunoassay (RIA) and CNP and AQP2 in urine were determined before and after
      the exercise test by RIA. RESULTS: The absolute increase in BNP during exercise
      was higher in patients with CHF (CHF: 4.1 pmol/l; healthy subjects: 1.3 pmol/l,
      P<0.05) and was positively correlated to BNP at rest (P<0.05), while the absolute
      increase in ANP during exercise was the same in the two groups (CHF: 4.2 pmol/l;
      healthy subjects: 6.8 pmol/l, not significant, NS). In CHF, exercise did not
      change either u-CNP excretion (rest: 9.8 ng/mmol creatinine; after exercise: 8.8
      ng/mmol, NS) or u-AQP2 (rest: 466 ng/mmol creatinine; after exercise: 517 ng/mmol
      creatinine, NS) as well as in healthy subjects where u-CNP (rest: 9.7 ng/mmol
      creatinine; after exercise: 9.2 ng/mmol creatinine) and u-AQP2 (rest: 283 ng/mmol
      creatinine; after exercise: 307 ng/mmol creatinine) were the same at rest and
      after exercise. CONCLUSION: The absolute increase in BNP during exercise is
      higher in patients with CHF compared to healthy subjects. It is suggested that
      this is a compensatory phenomenon to improve the exercise capacity in CHF, and
      that BNP is a more important factor in cardiovascular homeostasis during exercise
      in CHF than ANP.

PMID- 14975538
TI  - Common carotid intima-media thickness is correlated with myocardial flow reserve
      in patients with coronary artery disease: a useful non-invasive indicator of
      coronary atherosclerosis.
AB  - BACKGROUND: The common carotid intima-media thickness (IMT) is correlated with
      the angiographically determined coronary artery stenosis. However, their
      correlation is weak, which limits the clinical application of the IMT as a
      predictor of coronary artery stenosis. The IMT reflects diffuse early-phase
      atherosclerosis, whereas the angiographically determined coronary artery stenosis
      is a late-phase phenomenon. The latter is localized and rapidly progressive with
      plaque rupture and acute thrombosis. Instead of the angiographically determined
      coronary artery stenosis, we employed myocardial flow reserve (MFR) that reflects
      diffuse early-phase coronary atherosclerosis and impaired coronary vasodilatation
      function. We evaluated the relationship between the IMT and the MFR. METHODS:
      Twenty-three patients with angiographically diagnosed coronary artery disease
      (CAD) underwent B-mode ultrasound examination to measure their common carotid IMT
      and positron emission tomography (PET) with dipyridamole intervention to obtain
      their MFR. We also performed B-mode ultrasound examination in 21 patients with
      hypertension without CAD and in 15 control subjects. RESULTS: The common carotid
      IMT in patients with CAD was thickened (0.92+/-0.15 vs. 0.81+/-0.14 mm in
      patients with hypertension (P<0.05) and 0.69+/-0.13 mm in control subjects
      (P<0.01)). The IMT was inversely correlated with the MFR (r=0.51, P<0.01). The
      correlations between the MFR and most of the coronary risk factors (age, blood
      pressure, serum cholesterol level and triglyceride level, HbA1c level, smoking
      index) did not reach statistical significance. CONCLUSIONS: Thickened common
      carotid IMT is also an indicator of reduced MFR or early-phase coronary
      atherosclerosis.

PMID- 14975539
TI  - Incremental prognostic value of myocardial perfusion 99m-technetium-sestamibi
      SPECT in the elderly.
AB  - Coronary artery disease (CAD) is the main cause of death in elderly patients.
      Single-photon emission computed tomography (SPECT) with technetium-99m ((99m)Tc)
      labeled agents is extremely useful for the diagnosis and risk stratification of
      CAD in the general population. However, its prognostic value for the elderly has
      not been established. This study examined disease outcome in 328 patients aged 74
      or older, with suspected CAD who were submitted to either pharmacological
      (dipyridamole) or exercise stress SPECT with (99m)Tc-sestamibi, seven of whom
      were completely lost to follow-up. Endpoints were defined as hard (myocardial
      infarction or cardiac death) or total events (myocardial infarction, cardiac
      death or myocardial revascularization). Mean follow-up was 34+/-15 months. During
      this period 24 cardiac deaths, 11 myocardial infarctions and 21 cases of
      revascularization were observed. Perfusion defects were found in 27.1% of
      patients (12.8% reversible, 6.2% partially reversible and 8.1% fixed). Abnormal
      studies were predominant in men, patients with chest pain and those with ST-T
      abnormalities in the baseline electrocardiogram (ECG) or in the exercise
      treadmill test. An abnormal scan was significantly associated with cardiac events
      (P<0.0001). Multivariate analysis revealed that a abnormal scan was the most
      important independent predictor of hard or total cardiac events. Event rates
      increased according to myocardial perfusion scintigraphy (MPS): <1.0% of hard
      events per year in patients with normal MPS versus 14.3% per year in those with
      abnormal MPS. (99m)Tc-sestamibi SPECT was demonstrated to be a powerful tool for
      the prognostic evaluation of elderly patients with suspected CAD.

PMID- 14975540
TI  - Atrial septal defect in adults > or =40 years old: negative impact of low
      arterial oxygen saturation.
AB  - BACKGROUND: Although good prognosis and clinical long-term outcome have been
      commonly reported in minimally symptomatic adult patients with ASD, this
      information has been based on studies with a relatively small number of adult
      patients. We studied unoperated patients aged over 40 years to define the
      patterns of presentation, anatomical characteristics, outcome and predictive
      factors for free-event survival of major cardiovascular and pulmonary events.
      METHODS AND RESULTS: Two-hundred survivors of atrial septal defect aged over 40
      yr attended from 1985 to 1998 were reviewed and followed-up from 1.6 to 22 years.
      Patients were classified in three groups according to age at entry: Group 1,
      between 40 and 49; Group 2; 50 and 59; and Group 3, > or =60 years old. The mean
      age at presentation was 48.8+/-9.2 years, and the most common clinical
      presentations were arrhythmia and dyspnea (51.4%). There were 37 (18.5%) events:
      7 heart failure-related, 5 sudden death, 13 severe pulmonary infections, 5
      embolisms, and 4 strokes. According to Cox's regression analysis, predictors of
      primary end point included age group at presentation (hazard ratio 1.71, 95%
      confidence limits 1.16 to 2.54), and either pulmonary hypertension (mean
      pulmonary pressure >35 mmHg; hazard ratio=0.65 (4.6, confidence limits 2.2 to
      9.5) or, arterial oxygen saturation <80% (hazard ratio 1.71, 95% confidence
      limits 1.16 to 2.54). CONCLUSIONS: This study supports that long term outcome of
      patients aged >40 years with unoperated ASD is importantly determined by the mPAP
      (>35 mmHg), SaO2% (_80) and the age at diagnosis. Nevertheless we identified an
      inverse association between the mPAP level and SaO2% (interaction). The event
      free survival expectancy may be estimated using the age at diagnosis and either
      SaO2% or mPAP. This prognostic stratification based on pathophysiological
      principles, may help in making decisions for therapeutic interventions. SaO2%
      should always be measured as a part of the initial clinical approach of those
      patients with atrial septal defect aged over 40 years.

PMID- 14975541
TI  - Impact of the Gulf war on congenital heart diseases in Kuwait.
AB  - BACKGROUND: There has been concern over the increase in the number of babies born
      with congenital heart diseases (CHD) in Kuwait after the Gulf War. METHODS: We
      evaluated retrospectively the number of Kuwaiti infants who were diagnosed to
      have CHD within the first year of life. The comparison was made between those
      presented from January 1986 to December 1989 (preinvasion) and those presented
      after the liberation of Kuwait (from January 1992 to December 2000). The number
      of cases was considered per 10,000 live births in that year. RESULTS: The numbers
      of cases were 2704 (326 before the invasion and 2378 after liberation). The mean
      annual incidence of CHD was 39.5 and 103.4 (per 10,000 live births) before and
      after the Gulf War, respectively (P<0.001). There was an increase in the number
      of babies with CHD during the immediate 3 years postliberation with a relative
      reduction in the trend from 1995 to 2000, in some types of CHD. CONCLUSIONS: In
      our series, there was an increased incidence of CHD almost immediately following
      the end of the Gulf War period. The cause of this increase remains relatively
      obscure. Environmental pollution may be a contributing factor; others such as
      possible psychological trauma remain subject to speculation.

PMID- 14975542
TI  - Valsalva maneuver in chagasic patients with documented past medical history of
      acute chagasic myocarditis.
AB  - BACKGROUND: We studied the heart rate responses to the Valsalva maneuver in eight
      patients with documented past medical history of acute Chagas' disease. METHODS:
      Four patients were studied 8-21 months after the acute episode and four, 58-68
      months thereafter (age 25+/-8.65 years M+/-S.D.). Seventeen healthy subjects of
      similar age were included as controls (age 27+/-7.5 years, P=NS). RESULTS:
      Baseline heart rate was higher in chagasic patients (88+/-15 beats/min) compared
      to controls (69.8+/-9.8, P=0.001). Maximum heart rate at phase II of the maneuver
      was also higher (114+/-16.3 vs. 101.5+/-9.9, P=0.02). Minimum heart rate at phase
      IV was, however, not different (57.4+/-10.4 vs. 63.3+/-7.3 P=NS). The magnitude
      of the absolute negative change at phase IV was larger in the chagasic patients,
      although, not different (-50.8+/-13.8 vs. -44+/-13.8, P=NS). The Valsalva index
      was 1.81+/-0.26 in the chagasic patients and 1.82+/-0.42 in the controls (P=NS).
      Minimum heart rate at phase IV correlated neither with the baseline heart rate
      (r=-0.28, P=NS) nor with the Valsalva index (r=-0.40, P=NS). The magnitude of the
      absolute negative change during phase IV correlated with, both, the baseline
      heart rate (r=-0.80, P<0.01) and the Valsalva index (r=-0.95, P<0.0001). The
      higher baseline high rate influenced the magnitude of the negative heart rate
      change, but not the minimum heart rate reached at phase IV. CONCLUSIONS: Chagasic
      patients with proven past medical history of acute Chagas' disease had unimpaired
      heart responses to the Valsalva maneuver.

PMID- 14975543
TI  - Cigarette smoking and inflammatory indices in coronary artery disease.
AB  - BACKGROUND: Smoking-induced endothelial dysfunction may lead to inflammatory
      activation within a vascular wall mediated by cytokines and adhesion molecules.
      The aim of the study was to assess the relationship between the smoking status
      and serum levels of tumor necrosis factor (TNF) alpha, sTNFR 1 and 2 (soluble
      forms of TNF receptor), Interleukin (IL)-2, IL-10 and some selected adhesion
      molecules (AM): sE-selectin, sP-selectin, Vascular Cell AM-1 (sVCAM-1) and
      Intercellular AM-1 (sICAM-1) in patients with coronary artery disease (CAD).
      METHODS AND RESULTS: The study group consisted of 122 consecutive admissions with
      stable CAD (class II/III CCS): 31 current smokers (group I; mean age+/-S.E.M.:
      53.8+/-1.6 years), 38 ex-smokers (group II; mean age+/-S.E.M.: 57.8+/-1.4 years)
      and 53 patients who have never smoked (group III; mean age+/-S.E.M.: 62.4+/-1.1
      years). Serum concentration of IL-2 was higher in the group of active smokers
      (77.5+/-12.7 pg/ml) than in ex-smokers (40.0+/-10.6 pg/ml; P=0.017). AM
      determination also revealed differences between groups I and II-elevated serum sP
      selectin levels in active smokers (174.7+/-17.1 ng/ml) than in ex-smokers
      (123.5+/-10.3 ng/ml; P=0.024). Serum sTNFR 2 level was higher in group III
      (2457.3+/-120.5 pg/ml) in comparison to group II (2018.4+/-121.5 pg/ml; P=0.006).
      There were no differences between TNF alpha, sTNFR 1, IL-10, sE-selectin, sICAM
      1, sVCAM-1 levels in the groups examined. CONCLUSIONS: Cigarette smoking is
      associated with the elevation of IL-2 and sP-selectin serum levels in patients
      with stable CAD. CAD patients who have never smoked are characterized by delayed
      onset of angina and increased sTNFR 2 concentrations.

PMID- 14975544
TI  - Efficacy of folic acid when added to statin therapy in patients with
      hypercholesterolemia following acute myocardial infarction: a randomised pilot
      trial.
AB  - BACKGROUND: Folic acid is assumed to have favourable effects on vascular
      endothelium, directly as well as indirectly through its effect on homocysteine
      metabolism. However, the clinical value of folic acid in secondary prevention
      after acute myocardial infarction (MI) has never been tested. Thus, a randomised,
      open-label, multicentre trial was performed in order to study the effect of folic
      acid 5 mg o.d. when added to statin therapy on the incidence of recurrent major
      clinical events up to 1 year post-MI. METHODS: A total of 283 patients with a
      total cholesterol >6.5 mmol/l (251 mg/dl) (mean 7.3 mmol/l) were included. All
      patients received 40 fluvastatin. In 140 of the 283 patients, folic acid (5 mg
      o.d.) was instituted at discharge, and the remaining 143 patients served as
      controls. Other secondary prevention measures for both groups were advocated. The
      primary endpoint was a composite consisting of all vascular events, including
      death, recurrent MI, strokes, and unplanned invasive coronary interventions.
      RESULTS: At baseline, the two groups were well-matched for all clinical and
      demographic parameters. After 1 year of treatment, no difference was noticed in
      the primary endpoint between the two groups. These endpoints occurred in 43
      patients (31%) in the folic acid group, as opposed to 45 patients (31%) in the
      control group. All separate cardiovascular events were also equally distributed
      between both groups. Total cholesterol levels decreased to a similar extent in
      the two groups (to 5.5 and 5.7 mmol/l, in folic acid and control groups,
      respectively). CONCLUSIONS: In this medium-size pilot study, folic acid did not
      demonstrate any beneficial additive effects on cardiovascular mortality or
      morbidity in post-MI patients with hypercholesterolemia who were treated with
      statin therapy. Larger trials, possibly targeting at selected populations, must
      be awaited before definitive conclusions regarding the potentially favourable
      effects of folic acid supplementation in secondary prevention can be drawn.

PMID- 14975545
TI  - Clearance of a 3H-labeled chylomicron-like emulsion following the acute phase of
      myocardial infarction.
AB  - BACKGROUND: Plasma lipids may be altered during acute myocardial infarction and
      may not reflect patient baseline lipid profile. The metabolism of chylomicrons,
      the lipoproteins that carry the dietary lipids in the bloodstream has not yet
      been studied in acute myocardial infarction patients. METHODS: In this study, a
      lipidic emulsion that mimics the intravascular behavior of chylomicrons labeled
      with cholesteryl oleate ((3)H-CO) was injected intravenously in 17 normolipidemic
      patients on the seventh and on the 45th day post-non complicated acute myocardial
      infarction after a 12-h fast. The plasma decay curve of the emulsion label was
      determined from blood samples collected during 60 min. Data were also compared
      with a group of 10 patients with chronic coronary artery disease. RESULTS: In the
      acute myocardial infarction group, the plasma fractional catabolic rates of the
      emulsion (3)H-CO, expressed as median and confidence intervals, did not change
      from the seventh to the 45th day after the acute event [0.0773 (0.061, 0.1025)
      min(-1) vs. 0.0672 (0.00507, 0.1009) min(-1) P=0.61] and was similar to that
      determined in chronic coronary artery disease patients. High-density lipoprotein
      cholesterol and apolipoprotein AI were lower on the seventh day when compared to
      the 45th day post acute myocardial infarction (P=0.01 and P=0.004, respectively).
      No changes were found in LDL and total cholesterol as well as in plasma
      triglycerides in myocardial infarction group. CONCLUSIONS: No changes were found
      in chylomicron metabolism is in the acute phase of myocardial infarction.

PMID- 14975546
TI  - Cardiovascular autonomic function testing in asymptomatic T. cruzi carriers: a
      sensitive method to identify subclinical Chagas' disease.
AB  - BACKGROUND: Although impaired cardio-vagal response characterizes full-blown
      Chagas' disease, this feature among otherwise healthy T. cruzi serology carriers
      (SERO[+]) requires confirmation. The purpose of this study was to determine
      whether abnormal cardio-vagal responses were different among SERO[+] subjects
      with varying ECG alterations. METHODS: We assessed cardio-vagal reflex response
      in 57 randomly selected healthy blood donors (36 SERO[+], 15 with ECG
      rhythm/conduction abnormalities). The following cardiac autonomic tests were
      performed: (1) short-term heart rate variability (HRV), (2) Deep breathing test
      (DBT), (3) cold face test, (4) cold pressor test (CPT), (5) Valsalva maneuver,
      and (6) baroreflex sensitivity after administration of nitroprusside (BRS-NTP)
      and phenylephrine (BRS-PNP). RESULTS: Overall, SERO[+] subjects had 161/324
      (49.7%) abnormal responses, compared to 41/189 (21.7%) in SERO[-] (p<0.001).
      Similar rates were found in SERO[+] according to ECG status (68/135, 50.4% in
      ECG[+] and 93/189, 49.2% in ECG[-], p=0.836). Covariate-adjusted pooled odd
      ratios (95%CI) for abnormal responses compared to SERO[-] were: 2.73 (1.71-4.35)
      for SERO[+], and 2.63 (1.63-4.34) for SERO[+]/ECG[-] (p<0.001). BRS-NTP, CPT and
      DBT individually showed significant differences between SERO[-] and SERO[+]
      groups. Conversely, ECG changes among SERO[+] were not associated with a
      significant excess of autonomic abnormality either overall (OR=1.09, 95%CI: 0.67
      1.78, p=0.719) or by any individual test. CONCLUSIONS: Early cardio-vagal
      dysfunction was documented in SERO[+] subjects regardless of ECG status. Cardiac
      autonomic evaluation may be useful for identification of subclinical disease in
      SERO[+] subjects.

PMID- 14975547
TI  - Percutaneous transluminal septal myocardial ablation for hypertrophic obstructive
      cardiomyopathy; The Chinese experience in 119 patients from a single center.
AB  - BACKGROUND: Percutaneous transluminal septal myocardial ablation (PTSMA) has been
      introduced as an alternative treatment for hypertrophic obstructive
      cardiomyopathy (HOCM). We report on the acute, short- and long-term results of
      our experiences in 119 patients from a single center in China. METHODS AND
      RESULTS: PTSMA was performed in 119 patients with symptomatic HOCM (mean age
      35.4+/-14.8 years, male 80, female 39). All patients had echocardiography
      performed prior to the procedure, 2-week post-PTSMA, and 6-month post-PTSMA, and
      65 patients had echocardiography repeated at 2-year follow-up. The average left
      ventricular outflow tract (LVOT) gradient was 67.3+/-7.8 mm Hg before the
      procedure, and 15.9+/-6.8 mm Hg after the procedure (p<0.05). The thickness of
      interventricular septum (IVS) was 23.3+/-5.6 mm before the procedure, 18.6+/-4.8
      mm 2-week post-PTSMA (p<0.05), and 16.8+/-3.4 mm 6-month post-PTSMA in all of the
      patients, and 15.6+/-3.1 mm 2-year post-PTSMA in 65 patients. The mean width of
      LVOT was 6.7+/-2.0 mm before the procedure, 8.2+/-3.4 mm 2-week post-PTSMA
      (p<0.05), 13.7+/-6.3 mm 6-month post-PTSMA and 15.1+/-2.4 mm 2-year post-PTSMA.
      The incidence of right bundle branch block development post-PTSMA was 52.9%, and
      three patients (2.5%) had complete heart block. There was no death. CONCLUSIONS:
      PTSMA is a promising non-surgical procedure for symptomatic patients with HOCM
      because of its low risk and its significant hemodynamic, echocardiographic and
      clinical improvement. The significant therapeutic remodeling period was up to 6
      months rather than 2 years following the procedure.

PMID- 14975548
TI  - Body surface potential mapping improves detection of ST segment alteration during
      percutaneous coronary intervention.
AB  - BACKGROUND: The 12-lead electrocardiogram underestimates ST segment alteration in
      acute coronary syndromes compared with multi-lead body surface mapping. We
      assessed whether 80-lead mapping would improve detection of ST alteration during
      percutaneous coronary intervention. METHODS: Simultaneous maps and 12-lead
      electrocardiograms were recorded pre-procedure, during balloon inflation and post
      procedure from patients undergoing elective intervention to native coronary
      arteries. Recordings were obtained from 39 inflations (19 patients). All arteries
      were successfully stented. RESULTS: Mean 'lead specific' ST alteration (the
      difference in ST elevation/depression between pre-procedure and inflation
      recordings in the lead showing maximal ST alteration) was greater on the map than
      on electrocardiogram, both for ST elevation (0.16+/-0.02 vs. 0.06+/-0.01 mV;
      p<0.001) and ST depression (0.11+/-0.017 vs. -0.03+/-0.006 mV; p<0.001). During
      first inflations (n=19), mean lead specific ST elevation and depression on map
      were greater than on electrocardiogram (0.20+/-0.034 vs. 0.07+/-0.015 mV; p<0.001
      and 0.11+/-0.029 vs. 0.03+/-0.009 mV; p=0.001, respectively). Mapping detected
      greater summated ST elevation and depression during inflation than
      electrocardiogram (0.04+/-0.005 vs. 0.021+/-0.003 mV; p<0.001 and 0.026+/-0.004
      vs. 0.011+/-0.002 mV; p<0.001, respectively). Qualitative analysis of maps and
      electrocardiograms showed that 21/39 (53.8%) maps recorded during inflation met
      criteria for myocardial ischaemia compared with 7/39 (17.9%) electrocardiograms
      (p<0.001). CONCLUSION: Body surface mapping compared with the 12-lead
      electrocardiogram improves detection of myocardial ischaemia during intervention.

PMID- 14975549
TI  - Vascular endothelial growth factor: the link between cardiovascular risk factors
      and microalbuminuria?
AB  - BACKGROUND: Microalbuminuria, i.e. slightly elevated urinary albumin excretion,
      is associated with increased cardiovascular risk factors and cardiovascular
      morbidity in the general population. Microalbuminuria has been proposed to
      indicate increased endothelial permeability. Unknown are the mechanisms
      underlying this increased vascular permeability. Vascular endothelial growth
      factor (VEGF), also known as vascular permeability factor, increases endothelial
      permeability. We hypothesised that plasma VEGF levels may be associated with
      microalbuminuria in a large sample of the general population. METHODS: Out of a
      large sample of the general population, we studied 189 control subjects (urinary
      albumin excretion (UAE): 0-30 mg/24 h) and 194 microalbuminuric subjects (UAE: 30
      300 mg/24 h), matched for age, sex and the presence of ischemia on the
      electrocardiogram. RESULTS: Subjects with microalbuminuria had significant higher
      plasma levels of VEGF (p<0.05). The correlation between plasma levels of VEGF and
      systolic and diastolic blood pressure, cholesterol, glucose, diabetes and body
      mass index were statistically significant. Using logistic regression analysis,
      microalbuminuria was significantly associated with VEGF (odds ratio 1.62; 95%
      confidence interval: 1.15-2.27; p<0.01). This association was dependent on
      cardiovascular risk factors. CONCLUSION: This study suggests a relation between
      increased plasma VEGF levels and subsequent occurrence of microalbuminuria.

PMID- 14975550
TI  - Drug prescriptions and referral to cardiac rehabilitation after acute coronary
      events: comparison between men and women in the French PREVENIR Survey.
AB  - BACKGROUND AND AIM: The problem of a possible gender bias in coronary heart
      disease management is still controversial. We studied gender differences in
      secondary preventive drug prescriptions and in referral to cardiac rehabilitation
      after acute coronary events in France. METHODS: An observational survey was
      carried out in 1998-1999 in 150 French intensive cardiac care units. A sample of
      2626 consecutive patients admitted for myocardial infarction or unstable angina
      and alive at discharge was included. Data were retrospectively collected from
      medical records after discharge. RESULTS: The sample was composed of 1921 men and
      705 women. At discharge, antiplatelet agents were prescribed in 93.4% of men and
      91.5% of women (p=0.09), beta-blockers in 73.4% and 63.7% (p<0.0001), angiotensin
      converting enzyme (ACE) inhibitors in 39.9% and 44.3% (p<0.05), and statins in
      47.0% and 40.7% (p<0.01). The percentage of subjects referred to a cardiac
      rehabilitation program at discharge was 26.2% in men and 15.5% in women
      (p<0.0001). In multivariate analysis, taking into account confounding factors,
      gender did not appear as an independent determinant of drug prescriptions.
      Conversely, being a woman was independently associated with a lower probability
      to be referred to a cardiac rehabilitation program at discharge (adjusted female
      to-male odds ratio: 0.44 (95% confidence interval: [0.31-0.64], p<0.0001).
      CONCLUSIONS: In this study, gender was not an independent determinant of
      secondary preventive drug prescriptions after acute coronary events. Conversely,
      we found a gender bias in referral to cardiac rehabilitation programs at
      discharge.

PMID- 14975551
TI  - Contemporary outcome of cardiac catheterizations in 1085 consecutive
      octogenarians.
AB  - BACKGROUND: A growing number of patients > or = 80 years require cardiac
      catheterization. Since little is known about the overall safety of these
      procedures in this population, we assessed the procedure-related risks and
      determined predictors for complications. METHODS: We studied 1085 consecutive
      patients > or = 80 years (82.6+/-2.6 years; 526 males, 544 females), who
      underwent 1384 cardiac catheterizations in a tertiary specialist university
      hospital (3% of 43,517 procedures). RESULTS: A total of 373 patients (35%)
      required percutaneous coronary interventions (PCI), and 331 (31%) received
      coronary artery bypass surgery. Thirty-one patients died during hospital stay.
      Procedure-related complications including vascular injuries occurred in 2.1%
      after CATH and 11.6% after PCI. CONCLUSIONS: Despite the widespread notion that
      cardiac catheterization exposes patients > or = 80 years to an unwarranted risk,
      these data demonstrate an acceptable complication rate. Patients #10878;80 years
      of age should thus not be refused to undergo cardiac catheterization merely based
      on their age.

PMID- 14975552
TI  - Radiofrequency ablation of atrial fibrillation.
AB  - Twenty-five patients (16 males, mean age 46 years) underwent radiofrequency
      ablation because of either paroxysmal (13 patients) or persistent atrial
      fibrillation (12 patients). Ablation aimed at earliest activation of spontaneous
      and catheter-induced repetitive ectopy in left and right atria and appendages,
      and pulmonary veins. Catheter-induced repetitive ectopy was defined as acute
      onset of a burst of rapid atrial premature beats on touching the wall, sustained
      irritability while at the spot and acute termination of rapid activity upon
      release of the catheter. Post-ablation patients received antiarrhythmic drugs to
      prevent tachycardias, thereby allowing reversal of atrial remodeling. RESULTS:
      Lone atrial fibrillation was present in 19 patients, 4 patients had hypertension
      and 2 patients coronary artery disease with preserved left ventricular function.
      The median duration of the history of atrial fibrillation was 4 years (range 1-14
      years) and the median number of antiarrhythmic drug failures 5 (range 1-6).
      Ablation was successful, i.e. no recurrences of atrial fibrillation with or
      without antiarrhythmic drugs in eight patients (32%) during a median follow-up of
      28 months (range 18-52). The median number of foci was 3 (range 2-6) and 2 (range
      1-7) in the successfully and unsuccessfully treated patients, respectively. Minor
      complications occurred in three patients. CONCLUSIONS: Radiofrequency ablation of
      atrial fibrillation aiming at spontaneous and catheter-induced repetitive ectopy
      is a safe procedure. However, it is only successful in one third of the patients.
      Further investigations are warranted to identify the ideal patient, as well as to
      develop better ablation strategies.

PMID- 14975553
TI  - Reoperations in adults with congenital heart disease: analysis of early outcome.
AB  - BACKGROUND: Grown-ups with congenital heart disease (GUCH) are an increasingly
      important group of patients, with many requiring reoperations because of late
      complications or residual defects, correction after palliation, further
      palliation or heart transplantation. METHODS: In order to identify perioperative
      risk factors, we have retrospectively analysed perioperative mortality and
      morbidity of 66 consecutive GUCH patients needing reoperations between July 1987
      and December 2000 with a mean age of 28+/-12 (14.2-63.5) years and preoperative
      ejection fraction of 57+/-21%. Primary cardiac defects were LVOT pathology (17
      patients), coarctation (10), Tetralogy of Fallot (TOF) (9), VSD (9),
      transposition of the great arteries (TGA) (7), Marfan syndrome (6), ASD (5) and
      others (3). RESULTS: Reoperations included various aortic valve procedures (28),
      aortic replacements (16), ASD/VSD closures (16), conduits (11), RVOT procedures
      (8), coarctation repair (5), cardiac transplantation (3) or others (8). Early
      mortality was 7.6%. Serious postoperative complications occurred in 24%. Presence
      of cyanosis, heart failure, VSD, TGA, pulmonary atresia, correction after
      palliative surgery and number of previous operations were preoperative risk
      factors and duration of operation, cardiopulmonary bypass and aortic cross-clamp,
      core temperature, low output syndrome, use of epinephrine, pneumonia and ARDS,
      renal failure, dialysis and stroke perioperative risk factors for fatal outcome.
      CONCLUSIONS: Reoperations in GUCH patients are mostly due to outflow tract
      lesions, coarctations and TOF. Perioperative risks remain important especially
      with cyanosis, TGA, pulmonary atresia and poor ventricular function. Therefore,
      close follow-up, timely referral for re-intervention and adequate perioperative
      management are mandatory to reduce perioperative risks and improve results.

PMID- 14975554
TI  - Circadian variation of cardiac autonomic nervous activity is well preserved in
      patients with mild to moderate chronic heart failure: effect of patient position.
AB  - BACKGROUND: It remains unclear whether circadian variation (CV) of cardiac
      autonomic nervous activity (CANA) is preserved in patients with chronic heart
      failure (CHF) as in healthy subjects. We have demonstrated that CANA in CHF
      patients is largely affected by patient recumbent position. METHODS: We studied
      eight mild to moderate CHF patients and eight age, sex-matched healthy subjects.
      Each subject underwent 24-h ambulatory ECG monitoring. One channel was used to
      record the CM5 lead, and another to record the signal of patient position from a
      newly developed, small-sized detector. By using spectral analysis of heart rate
      variability, frequency-domain measures were calculated. Normalized high-frequency
      (HF: 0.15-0.40 Hz) power was used as an index of vagal activity and the low
      frequency (LF: 0.04-0.15 Hz)/HF power ratio was used as an index of sympathovagal
      balance. These indexes in the same recumbent position were compared between night
      (2:00-4:00 a.m.) and morning (6:00-8:00 a.m.). RESULTS: In healthy subjects, a
      definite CV of CANA was observed in each recumbent position. In patients with
      CHF, in each position, normalized HF power was lower in the morning than at
      night, whereas LF/HF was higher in the morning than at night. Thus, CANA in CHF
      patients is influenced not only by patient position but also by the time of day.
      CONCLUSION: CV of CANA in mild to moderate CHF patients is well preserved when
      taking patient position into consideration.

PMID- 14975555
TI  - Effect of atrial septal aneurysm on risk of cerebrovascular events in Japanese
      patients.
AB  - BACKGROUND: The aim of the present study was to determine whether atrial septal
      aneurysm (ASA) detected by transthoracic echocardiography (TTE) is an independent
      risk factor of cerebrovascular events for Japanese people. METHODS: A control
      study was conducted with 178 patients with ASA (follow-up rate, 96.7%; median
      follow-up period, 5.6 years) and 176 control patients (follow-up rate, 97.8%;
      median follow-up period, 5.4 years), selected from 42,528 consecutive patients
      who underwent TTE in the Omiya Medical Center, Jichi Medical School, from April
      1991 to March 2001. Data were collected by structured review of patient charts
      and a subsequent telephone survey. Long-term cerebrovascular risk factors were
      evaluated by logistic regression analysis. RESULTS: A previous episode of
      cerebral infarction had occurred in nine ASA patients (5.1%) and 11 control
      patients (6.3%). During the follow-up period, new cerebral infarction occurred in
      12 ASA patients (6.7%) and six control patients (3.4%). Only atrial fibrillation
      was found to be an independent risk factor of new cerebral infarction (OR, 5.06;
      95% CI, 1.32-19.46; P=0.04). CONCLUSIONS: ASA is not an independent risk factor
      of cerebrovascular events for Japanese patients. Thus, aggressive strategies such
      as anticoagulation are not essential for ASA patients without embolic episodes.

PMID- 14975556
TI  - Re-angioplasty of in-stent restenosis versus balloon restenoses--a matched pair
      comparison.
AB  - BACKGROUND: Despite different biological mechanisms involved in the restenotic
      process of in-stent restenosis and restenosis after balloon angioplasty alone,
      the occurrence of a second restenosis has been reported in the same range. There
      are no data available comparing the outcome after re-angioplasty of such lesions.
      We analyzed in a matched pair comparison the clinical outcome and angiographic
      long-term result of patients with balloon angioplasty of a first in-stent
      restenosis versus patients with balloon re-angioplasty of a first balloon
      restenosis. METHODS: Both groups consisted of 74 lesions matched by treated
      vessel, lesion location differentiated in proximal and non-proximal, and
      angiographic appearance of coronary artery disease differentiated in singular
      stenosis, diffuse or mixed pattern. Clinical follow-up was 100%. Angiographic
      follow-up was 78.4% after median 174 days. RESULTS: Angiographic restenosis rate
      in matched pairs of patients (n=46/74) was significantly higher in the balloon
      restenosis group (41.3%, n=19/46) compared to the in-stent restenosis group
      (21.7%, n=10/46, p<0.042). There was no death or myocardial infarction. After
      clinical follow-up, target lesion revascularization rate was significantly lower
      in the in-stent restenosis group compared to the balloon restenosis group (12.1%,
      n=9/74 versus 27.0%, n=20/74; difference between groups 14.9%, 95% confidence
      interval 2.0-27.3%, p<0.023). Multivariate logistic regression analysis revealed
      as predictors for a second restenosis unstable angina pectoris, non-proximal
      lesion, restenosis after balloon angioplasty and the occurrence of the first
      restenosis within 90 days after initial intervention. CONCLUSION: Clinical and
      angiographic outcome after balloon angioplasty of a first in-stent restenosis was
      significantly better compared with balloon re-angioplasty of a first balloon
      restenosis.

PMID- 14975557
TI  - Risk stratification and survival in post myocardial infarction patients: a large
      prospective and multicenter study in Japan.
AB  - BACKGROUND: Recent clinical trials suggest that the mortality in high-risk
      patients with ischemic heart disease can be significantly reduced with the use of
      implantable cardioverter-defibrillator (ICD). Given the high cost and
      invasiveness of the procedure, it is important to apply it to the patients after
      myocardial infarction (MI) highly susceptible to sudden arrhythmic death.
      OBJECTIVE: The purpose of this study was to assess clinical predictors of
      mortality in post-MI patients in Japan. METHODS AND RESULTS: In 495 consecutive
      MI survivors, 350 (71%) received acute-reperfusion therapy, whereas 145 (29%) did
      not. Nonsustained ventricular tachycardia (NSVT) was present in 136 patients
      (28%) in 24-h ambulatory ECGs at 7+/-6 in-hospital days. Left ventricular
      dysfunction (LVEF< or =35%) was present in 20/347 patients (5.7%) at 13+/-8 days.
      Forty-eight patients (9.7%) died during the follow-up period (48+/-13 months); 23
      from cardiac and 25 from noncardiac causes. Kaplan-Meier survival analyses showed
      that mortality rates were higher among patients who were > or =70 years old (log
      rank test, P<0.0001); had heart failure at admission (Killip scale> or =2,
      P=0.001); did not receive acute-reperfusion (P=0.004); and had left ventricular
      dysfunction with LVEF< or =35% (P=0.02). The presence of NSVT was a significant
      predictor of death (P=0.036) only in the patients who did not receive acute
      reperfusion. Multivariate Cox regression analysis revealed that an independent
      predictor of total mortality was an age> or =70 (odds ratio, 1.06; 95% confidence
      interval, 1.01-1.11; P<0.00001). CONCLUSIONS: High-risk patients after acute MI
      can be identified on the basis of age, ventricular dysfunction, heart failure and
      acute-reperfusion therapy. The presence of NSVT before discharge has a prognostic
      value only in the patients without acute-reperfusion.

PMID- 14975558
TI  - Significance of extension of exercise-induced ischemia toward apex of left
      ventricle.
AB  - BACKGROUND: The aim of this study was to evaluate the significance of extension
      of exercise-induced ischemia toward apex of left ventricle. METHODS: After
      injections of technetium-99m tetrofosmin at peak ergometer exercise and thallium
      201 at 3 min post-exercise, dual-isotope single photon emission computed
      tomography (SPECT) images were obtained simultaneously with cross-talk
      compensation using triple-energy window in 70 patients (65.8+/-9.5 years) with
      angiographically proven ischemic heart disease. The left ventricle was divided
      into a total of 18 areas in 3 levels of apical, middle, basal, and the extent and
      localization of ischemia to long axis of left ventricle were measured at peak
      exercise and 3 min into the recovery. RESULTS: Of 57 patients with exercise
      induced reversible ischemia, in 25 patients with the ischemia in 2 levels to long
      axis of left ventricle, the ischemia extended mainly to the middle and basal
      levels (p<0.0001) and was localized during recovery mainly in the basal level
      (p<0.0005). In 21 patients with the ischemia in all 3 levels, the ischemia was
      localized during recovery mainly to the middle and basal levels (p<0.05). The
      persistence of ischemia in apex at post-exercise reflected the delay of recovery
      from ischemia on the whole of left ventricle and was related to the enlargement
      of resting end-diastolic volume of left ventricle as compared to the quick
      recovery of ischemia in apex (p<0.0005 and p<0.05, respectively). CONCLUSIONS:
      Although the ischemia recovers earliest in the peripheral apical level within
      exercise-induced ischemic territory, the delay of recovery from the ischemia in
      the apical level may be related to the development of heart failure, independent
      of intensity of occurred ischemia during exercise.

PMID- 14975559
TI  - Pericardial fluid level of heart-type cytoplasmic fatty acid-binding protein (H
      FABP) is an indicator of severe myocardial ischemia.
AB  - BACKGROUND: Heart-type cytoplasmic fatty acid-binding protein (H-FABP) has been
      reported as a sensitive and specific marker for the early diagnosis of acute
      myocardial infarction. Our hypothesis was that serum or pericardial fluid levels
      of H-FABP can reflect not only myocardial infarction but also myocardial
      ischemia. METHODS: A total of 34 patients with unstable angina, who had anginal
      symptoms and/or ST-changes in ECG monitoring within 24 h before operation, were
      classified into group A (n=17), and those without these symptoms and changes into
      group B (n=17). Blood and pericardial fluid samples were obtained immediately
      after median sternotomy, and serum and pericardial fluid levels of creatine
      kinase-MB, cardiac troponin-T, and H-FABP were measured. RESULTS: Serum H-FABP
      levels were slightly elevated compared with their normal values in both groups.
      While they showed no difference between groups A and B (group A vs. B: 8.5+/-1.0
      vs. 7.1+/-0.7 ng/ml, P=0.25), pericardial fluid levels of H-FABP were
      significantly higher in group A than in group B (16.3+/-2.0 vs. 9.6+/-1.0 ng/ml,
      P=0.0046). H-FABP showed a weak correlation between its serum levels and
      pericardial fluid levels (r=0.40). CONCLUSIONS: Pericardial fluid levels of H
      FABP reflect myocardial ischemia occurring within 24 h of their measurements. H
      FABP may be secreted into the interstitial space by increased permeability of the
      myocardial cell membrane associated with severe myocardial ischemia. Thus,
      pericardial fluid reflects pathophysiological conditions of cardiomyocytes more
      sensitively than circulating blood.

PMID- 14975560
TI  - Accessory pathway associated with an anomalous coronary sinus.
AB  - Congenital coronary sinus anomalies are unusual and they rarely coexist with
      accessory atrioventricular pathways. These anomalies are generally asymptomatic,
      however they can cause difficulty in mapping. The association between accessory
      pathway and coronary sinus anomalies may suggest an embryologic link. In this
      case, we report a male patient with permanent form of reciprocating tachycardia
      coexistent with anomalous coronary sinus.

PMID- 14975561
TI  - Floating thrombi on the Eustachian valve as a complication of venous
      thromboembolic disease.
AB  - Floating right heart thrombi can occur in 4-18% of patients with pulmonary
      embolism. Usually, the diagnosis is done by echocardiography and carries an
      important prognostic significance as thrombi can embolize at any moment and
      severe pulmonary embolism is the most frequent way of floating right heart
      thrombi presentation (mortality rate >40%). We present a case report of floating
      right thrombi in a patient with proven deep venous thrombosis complicated with
      nonmassive pulmonary embolism that was successfully treated with thrombolysis.

PMID- 14975562
TI  - Left-sided or transposed inferior vena cava ascending as hemiazygos vein and
      draining into the coronary sinus via persistent left superior vena cava: case
      report.

PMID- 14975563
TI  - Nobody is perfect--a pacemaker dysfunction.

PMID- 14975564
TI  - Takayasu's arteritis with bilateral renal artery stenosis: unilateral kissing
      balloon angioplasty.

PMID- 14975566
TI  - Fate of internal mammary artery grafted on to totally occluded coronary arteries.

PMID- 14975565
TI  - Cocaine and accelerated atherosclerosis: insights from intravascular ultrasound.

PMID- 14975567
TI  - Hyperkalemia in fatal MDMA ('ecstasy') toxicity.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is an amphetamine synthetic
      analog widely used as an recreational drug. Acute and severe toxic effects
      following MDMA ingestion include hyperthermia, arrhythmias, rhabdomyolisis,
      disseminated intravascular coagulation, hepatotoxicity and even death. Recently,
      we treated a patient in whom hyperkalemia, in the absence of renal failure,
      aggravated the expected toxic complications of MDMA, becoming the immediate cause
      of his death.

PMID- 14975568
TI  - Diastolic heart failure in female patient 20 years after radiotherapy due to
      Hodgkin's disease-a case report.
AB  - We present the case of a 36-year-old female with severe heart failure which
      developed 20 years after irradiation due to Hodgkin's disease.

PMID- 14975569
TI  - A new hereditary form of ectopic atrial tachycardia with autosomal dominant
      inheritance.
AB  - We report a family with a previously not described hereditary form of ectopic
      atrial tachycardia. The tachycardia had an autosomal dominant mode of
      inheritance, was not associated with structural heart disease and had a benign
      course.

PMID- 14975570
TI  - Epsilon wave.

PMID- 14975571
TI  - Brucella endocarditis complicated with a mycotic aneurysm of the superior
      mesenteric artery: a case report.
AB  - Brucella endocarditis, although a rare complication of brucellosis, is the main
      cause of death attributable to this disease. Mycotic aneurysm is an important
      extracardiac complication of infective endocarditis. Mycotic aneurysm of the
      superior mesenteric artery is extremely rare. In the present case, we report a
      patient with Brucella melitensis endocarditis complicated with a superior
      mesenteric artery aneurysm. To our knowledge, this is the first such reported
      case.

PMID- 14975572
TI  - Nonocclusive subacute stent thrombosis as a source of distal macroembolism.

PMID- 14975573
TI  - Effect of homocysteine-lowering vitamin treatment on electrocardiography stress
      tests in a randomized, placebo-controlled trial: comparison between ST-segment
      changes and Athen QRS-score.

PMID- 14975574
TI  - Clinical importance of the initiation pattern of monomorphic ventricular
      tachycardia.
AB  - We investigated the clinical and electrophysiological features of monomorphic
      ventricular tachycardia (MVT) with different initiation patterns in patients with
      implantable cardioverter defibrillator to assess whether there is a relationship
      between the initiation patterns of sustained MVT and clinical characteristics,
      and the efficacy of antiarrhythmic and electrical therapy. Fifty-five stored
      IECGs in twenty-two patients with MVT were evaluated. All MVT episodes were
      classified as initiating with ventricular premature beats (non-sudden onset MVT)
      or without ventricular ectopy preceding tachycardia (sudden onset MVT). Non
      sudden onset MVT was characterized by shorter tachycardia cycle length (CL) and
      required higher shock energy for termination. Sudden onset MVT was precipitated
      by shortening of the sinus CL before tachycardia and was more common with
      relatively better preserved systolic function.

PMID- 14975575
TI  - Mechanism of spontaneous diminution of mitral regurgitation following
      percutaneous mitral valvuloplasty with the Inoue balloon.

PMID- 14975576
TI  - Secondhand smoke and cardiologists: the missing link.

PMID- 14975578
TI  - Fatal potential of supraventricular tachycardia in hypertrophic cardiomyopathy.

PMID- 14975579
TI  - Atrial septal defect in apical hypertrophic cardiomyopathy associated with
      coronary spasm.
AB  - Apical hypertrophic cardiomyopathy (HCM) is a well-known myocardial disease, but
      the additional coexistence of an atrial septal defect (ASD) and coronary spasm is
      quite rare. We report here on a 62-year-old man suffering from congestive heart
      failure due to apical HCM complicated by coronary spasm and secundum-type ASD.
      The transthoracic, transesophageal echocardiography and cardiac catheterization
      were useful for diagnosing and evaluating of the patient's status. A calcium
      channel blocker was given to prevent coronary spasm, and a surgical patch closure
      operation was successfully performed. Afterwards, his symptoms were alleviated.

PMID- 14975580
TI  - Successful catheter ablation of ventricular tachycardia originating from the
      idiopathic saccular apical left ventricular aneurysm.
AB  - Left ventricular (LV) aneurysm has been recognized to frequently become a
      substrate of ventricular tachyarrhythmias. We report a case of a 66-year-old
      woman with symptomatic sustained monomorphic ventricular tachycardia (SMVT)
      originating from saccular apical LV aneurysm without definite underlying
      diseases. We performed catheter ablation using electroanatomical and conventional
      bipolar potential mapping. During SMVT, we found an area of fragmented potential 
      40 ms preceding the earliest wide QRS complex in the area of the apical LV
      aneurysm. Radiofrequency applications were delivered to this area. Since then,
      SMVT was no longer inducible by programmed electrical stimulation. The patient
      has remained free of VT recurrences during a subsequent 12-month follow-up
      period.

PMID- 14975581
TI  - T cell and antibody responses in remitting-relapsing experimental autoimmune
      encephalomyelitis in (C57BL/6 x SJL) F1 mice.
AB  - To characterize T cell and antibody responses in remitting-relapsing experimental
      autoimmune encephalomyelitis (RR-EAE), we compared myelin oligodendrocyte
      glycoprotein (MOG)-induced RR-EAE in C57BL/6 (B6) x SJL (F1) mice and chronic
      progressive EAE (CP-EAE) in B6 mice at week 8 p.i. when clinical scores were
      comparable. Although these two strains exhibited similar
      inflammation/demyelination pattern and MOG-induced T cell responses, RR-EAE mice
      produced significantly higher levels of anti-MOG IgG1/IgG2a antibodies. Further,
      lymphocytes of RR-EAE mice proliferated vigorously to the secondary epitope
      myelin basic protein (MBP) 1-11. These results support a potential involvement of
      anti-MOG antibodies and epitope spreading in T cell responses in the development
      of MOG-induced RR-EAE model.

PMID- 14975582
TI  - Intracerebral expression of CXCL13 and BAFF is accompanied by formation of
      lymphoid follicle-like structures in the meninges of mice with relapsing
      experimental autoimmune encephalomyelitis.
AB  - Given the abnormalities in B-cell activity occurring in the central nervous
      system (CNS) of patients with multiple sclerosis (MS), we have explored the
      possibility that CNS inflammation induced in mouse models of experimental
      autoimmune encephalomyelitis (EAE) triggers expression of molecules that control
      the development and functional organization of lymphoid follicles, the sites
      where B-cell responses are initiated. By reverse transcription-polymerase chain
      reaction (RT-PCR), we find that gene expression of CXCL13, a chemokine involved
      in B-cell recruitment into lymphoid follicles, and BAFF, a key regulator of B
      cell survival, is markedly and persistently upregulated in the CNS of mice with
      relapsing-remitting and chronic-relapsing EAE. Using immunohistochemical
      techniques, we also show the presence of lymphoid follicle-like structures
      containing B cells and a reticulum of CXCL13+ and FDC-M1+ follicular dendritic
      cells within the meninges of several mice undergoing progressive relapsing EAE.
      These observations indicate that, under chronic inflammatory conditions, the less
      immunoprivileged meningeal compartment is the site where ectopic lymphoid
      follicles preferentially develop and where pathogenic B-cell responses could be
      sustained in autoimmune disorders of the CNS.

PMID- 14975583
TI  - Triptolide, a Chinese herbal extract, protects dopaminergic neurons from
      inflammation-mediated damage through inhibition of microglial activation.
AB  - Mounting lines of evidence have suggested that brain inflammation participates in
      the pathogenesis of Parkinson's disease. Triptolide is one of the major active
      components of Chinese herb Tripterygium wilfordii Hook F, which possesses potent
      anti-inflammatory and immunosuppressive properties. We found that triptolide
      concentration-dependently attenuated the lipopolysaccharide (LPS)-induced
      decrease in [3H]dopamine uptake and loss of tyrosine hydroxylase-immunoreactive
      neurons in primary mesencephalic neuron/glia mixed culture. Triptolide also
      blocked LPS-induced activation of microglia and excessive production of TNFalpha
      and NO. Our data suggests that triptolide may protect dopaminergic neurons from
      LPS-induced injury and its efficiency in inhibiting microglia activation may
      underlie the mechanism.

PMID- 14975584
TI  - Intraparenchymal administration of interleukin-1beta induces cyclooxygenase-2
      mediated expression of membrane- and cytosolic-associated prostaglandin E
      synthases in mouse brain.
AB  - Interleukin (IL)-1beta is a proinflammatory cytokine expressed in neural tissue
      following injury and in neurodegenerative states. To understand the consequences
      of its presence in brain, we carried out intraparenchymal IL-1beta injections and
      found significant increases in prostaglandin (PG)E2, a critical factor in
      inflammatory and physiological processes. Elevated mRNA and protein expression of
      the PGE2-synthetic-related enzymes cyclooxygenase (COX)-2 and membrane-associated
      PGE synthase (PGES) accompanied local PGE2 production. In addition, IL-1beta
      stimulated protein expression of cytosolic PGES. Finally, we showed attenuation
      of these IL-1beta-inductions by COX-2 inhibition, suggesting in vivo regulation
      of both PGE synthase isoforms in the brain.

PMID- 14975585
TI  - Deficient p75 low-affinity neurotrophin receptor expression exacerbates
      experimental allergic encephalomyelitis in C57/BL6 mice.
AB  - We have investigated the role of p75NTR in inflammation in experimental allergic
      encephalomyelitis (EAE), a model for the human disease multiple sclerosis (MS).
      Induction of EAE in C57/BL6 wild-type mice resulted in expression of p75NTR in
      endothelial cells in the CNS. In contrast to the clinical manifestation of EAE
      observed in wild-type C57/BL6 mice, mice deficient for p75NTR (p75NTR knockout
      mice) developed severe or lethal disease and concomitant increased levels of
      inflammation in the CNS. Our findings suggest a physiological significant role
      for p75NTR in CNS endothelial cells during inflammation and involvement in
      preservation of blood-brain barrier integrity during a severe infiltrative
      attack.

PMID- 14975586
TI  - Morphine-induced alterations of immune status are blocked by the dopamine D2-like
      receptor agonist 7-OH-DPAT.
AB  - Morphine administration produces profound effects on the immune system, including
      reductions in natural killer cell activity, mitogen-induced lymphocyte
      proliferation, and cytokine production. Although it has been established that the
      activation of central nervous system (CNS) micro-opioid receptors by morphine
      induces immunomodulation, little is known about the neural mechanisms underlying
      such processes. Interestingly, it has been shown that the dopamine (DA) D2-like
      receptor agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) blocks the
      effect of morphine on a number of behaviors that are mediated by central dopamine
      pathways. The present study examined whether dopamine is involved in the
      immunomodulatory effects of morphine. In separate experiments, 7-OH-DPAT was
      administered either systemically (subcutaneous, s.c.) or centrally
      (intracerebroventricularly, i.c.v.) prior to morphine treatment in male Lewis
      rats. The results demonstrate that both systemic and central administration of 7
      OH-DPAT attenuate the suppressive effect of morphine on several measures of
      immune status. Overall, these findings provide the first evidence that CNS
      dopaminergic mechanisms are directly involved in morphine-induced
      immunomodulation.

PMID- 14975587
TI  - Induction of IL-10 in rat peritoneal macrophages and dendritic cells by
      glatiramer acetate.
AB  - Glatiramer acetate (GLAT) is a mixture of basic polypeptides that have been shown
      to suppress experimental autoimmune encephalomyelitis (EAE). As Copaxone, GLAT is
      approved for the treatment of relapsing-remitting multiple sclerosis (MS).
      Different immunomechanisms have been suggested to contribute to the beneficial
      effects of GLAT which rely on blockade of MHC class II molecules or cross
      recognition with myelin basic protein (MBP). Because GLAT could also inhibit
      experimental autoimmunity not related to myelin proteins, we searched for
      additional, less-restricted immunomodulatory actions of GLAT. Using freshly
      isolated resident peritoneal macrophages from naive Lewis rats, it is shown that
      GLAT profoundly modulates cytokine secretion of the cells. In unseparated
      macrophages (MPhi) and MPhi of low density, GLAT enhanced constitutive and LPS
      induced production of interleukin 10 (IL-10) while LPS-induced synthesis of tumor
      necrosis factor-alpha (TNF-alpha) was dose-dependently suppressed by GLAT.
      Although both basic proteins GLAT and MBP facilitated adherence of MPhi, MBP had
      opposite effects on cytokine production suggesting unique properties of GLAT. In
      contrast to MPhi, peritoneal mast cells produced only little amounts of
      cytokines. The inductive effect of GLAT on IL-10 production by antigen-presenting
      cells was also observed in bone marrow-derived rat dendritic cells (DCs) which,
      unlike MPhi, were not suppressed in their production of TNF-alpha. Induction of
      IL-10 in different antigen-presenting cells is a new immunomodulatory mechanism
      of GLAT. In part, it goes along with the inhibition of TNF-alpha and may be a
      common basis for the known beneficial effects of GLAT on various cellular
      autoimmune responses including MS.

PMID- 14975588
TI  - Social stress alters the severity of acute Theiler's virus infection.
AB  - Our laboratory has previously shown that restraint stress resulted in decreased
      Theiler's virus-induced CNS inflammation, while exacerbating illness behaviors
      during the acute phase of disease. In contrast, social disruption stress (SDR)
      applied prior to infection led to the development of glucocorticoid (GC)
      resistance, and these animals developed more severe disease course, with
      increased inflammation. However, when SDR was applied concurrent with infection,
      GC resistance fails to develop, disease course is less severe and inflammation
      was moderate. These results suggest that the effects of SDR on Theiler's virus
      infection are dependent upon the timing of SDR application in relation to
      infection.

PMID- 14975589
TI  - Morphine modulates HIV-1 gp160-induced murine macrophage and human monocyte
      apoptosis by disparate ways.
AB  - We studied the effect of HIV-1 gp160 protein and morphine on murine macrophage
      and human monocyte apoptosis. gp160 not only promoted murine macrophage apoptosis
      but also enhanced macrophage iNOS expression/NO generation. gp160 also altered
      macrophage bax and bcl-2 expression. Morphine enhanced (P<0.001) the effect of
      gp160 on macrophage apoptosis as well as iNOS expression/NO generation.
      Nevertheless, both morphine- and gp160-induced murine macrophage apoptosis was
      attenuated by nitric oxide synthase (NOS) inhibitors (L-NAME and L-NMMA). On the
      other hand, free radical scavengers such as superoxide dismutase (SOD),
      dimethylthiourea (DMTU) and catalase attenuated morphine and gp160-induced human
      monocyte apoptosis.

PMID- 14975590
TI  - Thymic myoid cells express high levels of muscle genes.
AB  - To explore the possible contribution of thymic myoid cells in tolerance induction
      mechanisms, we quantified by real-time RT-PCR, the expression of 12 muscle genes
      (the five subunits of acetylcholine receptor, Musk, rapsyn, utrophin, ErbB2,
      ErbB3, troponin T, and MCK) in a human thymic myoid cell line (MITC), compared to
      thymic epithelial cells (TEC) and thymocytes. Although expression of all the
      genes analyzed was detected in TEC and thymocytes, the level of expression in
      these cells was much lower than in MITC, except for -AChR, utrophin and ErbB3
      genes. Since myoid cells express high level of most muscle genes and are
      consistently found in the thymic medulla, they may contribute to the mechanisms
      involved in the induction and maintenance of immune tolerance.

PMID- 14975591
TI  - Effects of repeated social stress on leukocyte distribution in bone marrow,
      peripheral blood and spleen.
AB  - Leukocyte trafficking between the various body compartments has an important
      surveillance function that ensures the detection of antigen and enables the
      immune system to initiate a rapid and effective response. Repeated social defeat
      of group-housed male mice induced by daily, acute encounters with an aggressive
      conspecific substantially altered leukocyte trafficking and led to a gradual
      redistribution of immune cells in bone marrow, peripheral blood and spleen.
      Recurrent exposure to the stressor over a period of 2, 4 or 6 consecutive days
      was associated with cell mobilization and increased myelopoiesis in the bone
      marrow that was paralleled by an accumulation of neutrophils and monocytes in
      circulation and spleen. Substantial depletion of B cells in bone marrow and blood
      was associated with an increase in splenic B cells indicating a redirection of
      this cell type to the spleen. In contrast, T cells were markedly reduced in these
      immune compartments. The recruitment of CD11b+ leukocytes (i.e.,
      monocytes/macrophages and neutrophils) from the bone marrow to the spleen might
      play a critical role in the development of functional glucocorticoid resistance
      in the murine spleen that was reported in context with repeated social defeat.

PMID- 14975592
TI  - Ligands for the peroxisome proliferator-activated receptor-gamma and the retinoid
      X receptor exert additive anti-inflammatory effects on experimental autoimmune
      encephalomyelitis.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the
      nuclear-receptor superfamily that binds to DNA with retinoid X receptors (RXRs)
      as PPAR-RXR heterodimers. In experimental autoimmune encephalomyelitis (EAE), the
      gene expression of PPAR-gamma was demonstrated in spinal cord during the course
      of EAE. Administration of 15-deoxy-(12,14)-prostaglandin J2 (15d-PGJ2) or 9-cis
      retinoic acid (RA) alone at the onset of clinical signs of EAE reduced the
      severity of disease, however, their combination resulted in enhanced amelioration
      of disease. These results suggest that use of RXR specific ligands may be highly
      effective when combined with PPAR-gamma agonists in the treatment of autoimmune
      demyelinating diseases such as multiple sclerosis (MS).

PMID- 14975593
TI  - TNF-related apoptosis-inducing ligand mediates human neuronal apoptosis: links to
      HIV-1-associated dementia.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is a type II integral membrane
      protein that interacts with multiple receptors and cell types including neurons.
      In this report, TRAIL protein levels were increased in human monocyte-derived
      macrophages (MDM) after HIV-1 infection and immune activation. In HIV-1
      encephalitic (HIVE) human brain tissue, TRAIL-expressing macrophages were found
      in association with active caspase-3 positive neurons. Cytotoxic TRAIL receptors
      1 and 2 were expressed on neurons in primary human fetal cultures and HIV-1
      encephalitic brain tissue. Furthermore, TRAIL induced a dose-dependent effect on
      neuronal apoptosis. These results support a role for TRAIL in mononuclear
      phagocyte (MP)-mediated neurotoxicity in HIV-1-associated dementia (HAD).

PMID- 14975594
TI  - Central but not the peripheral action of cholinergic compounds suppresses the
      immune system.
AB  - Cholinergic compounds modulate the immune system; however, the mechanism of
      cholinergic immunotoxicity is largely unknown. Lewis rats were exposed
      chronically to cholinergic compounds via subcutaneous or intracerebroventricular
      routes. Compounds that crossed the blood-brain barrier (BBB) inhibited the
      antibody response when given by either route, however, poorly permeable
      compounds, unless given in high doses, inhibited the antibody response only by
      intracerebroventricular administration. Intracerebroventricular administration of
      cholinergic agents also reduced serum corticosterone levels, which along with the
      antibody response was attenuated by pretreatment with the ganglionic blocker
      chlorisondamine. Thus, cholinergic agents affect the neuroimmune communication
      and inhibit glucocorticoid production; the latter may be a biomarker for
      cholinergic toxicity.

PMID- 14975595
TI  - Alpha-lipoic acid is effective in prevention and treatment of experimental
      autoimmune encephalomyelitis.
AB  - Alpha-lipoic acid (alpha-LA) is a neuroprotective metabolic antioxidant that has
      been shown to cross the blood brain barrier. We tested whether alpha-LA is
      capable to prevent MOG35-55-induced experimental autoimmune encephalomyelitis
      (EAE), an established model of multiple sclerosis (MS). Daily oral administration
      of alpha-LA, starting at the time of immunization, significantly prevented EAE
      progression as compared to control mice. This was associated with a reduction of
      CNS infiltrating T cells and macrophages as well as decreased demyelination. We
      then tested alpha-LA in a therapeutic protocol aimed at suppressing EAE after its
      onset. Intraperitoneal (i.p.), but not oral, administration of alpha-LA
      significantly prevented disease progression when compared to vehicle-treated
      controls. Similarly, we observed significant reduction of demyelination and
      inflammatory infiltration. This clinical effect was not due to an impairment of
      MOG35-55 recognition by encephalitogenic T cells. In contrast, MOG-specific T
      cells showed a decreased production of IFNgamma and IL-4, suggesting an
      immunosuppressive activity on both Th1 and Th2 cytokines. In addition, alpha-LA
      inhibited the proteolytic activity of MMP2 and MMP9 only at very high doses. Our
      data indicate that alpha-LA can effectively interfere with the autoimmune
      reaction associated with EAE through mechanisms other than its antioxidant
      activity and supports further studies on the use of alpha-LA as a potential
      therapy for MS.

PMID- 14975596
TI  - The MBP-reactive repertoire is shaped by recognition of minor histocompatibility
      antigens.
AB  - While it is known that the degeneracy of T-cell antigen recognition is involved
      in many aspects of T cell-immunology, its importance in the selection of the T
      cell repertoire remains an aspect to be better investigated. Here we examined if
      an intrathymic degenerate T cell recognition mechanism shapes the myelin basic
      protein (MBP)-reactive repertoire inducing resistance to experimental autoimmune
      encephalomyelitis (EAE) in some MHC and/or minor histocompatibility antigens
      (MiHAs) heterozygous F1 mice bearing the H-2(s) susceptibility allele. We found a
      considerable degree of cross-reactivity between MBP and MiHAs encoded in various
      EAE resistant mouse strains: (1) MBP-specific T cells can be re-stimulated in
      vitro by cells expressing these MiHAs and maintain their encephalitogenic
      activity, and (2) lymphoid cells from parental strains that generate EAE
      resistant F1 hybrids can induce disease relapse when injected into EAE
      susceptible hosts. The results suggest that heterozygosity, through the
      degeneracy of T cell antigen recognition mechanism, may provide further means to
      constrain the potential autoreactive repertoire.

PMID- 14975597
TI  - Treatment with an acetylcholinesterase inhibitor in Alzheimer patients modulates
      the expression and production of the pro-inflammatory and anti-inflammatory
      cytokines.
AB  - Elevated levels of cytokines have been detected in brains of Alzheimer's disease
      (AD) patients, and altered peripheral levels of IL-1beta, TNFalpha and IL-6 have
      been reported in these patients. We studied the ability of PBMC from patients
      with AD, matched with a control group, to release pro- and anti-inflammatory
      cytokines, and the effect of AChEI treatment on cytokine release. Our data
      indicates that AChEI treatment down-regulates IL-1, IL-6 and TNF, and up
      regulates the expression and production of IL-4 in PBMC in AD patients, and that
      AChEI leads to the remodelling of the cytokine network, probably acting on the
      lymphocytic cholinergic system.

PMID- 14975598
TI  - Monocyte activation and disease activity in multiple sclerosis. A longitudinal
      analysis of serum MRP8/14 levels.
AB  - In active multiple sclerosis (MS) lesions macrophages expressing myeloid related
      protein (MRP) 8/14 are present. The aim of this study was to determine whether
      serum levels of MRP8/14 complexes are related to disease activity in MS. In a
      longitudinal study of 16 relapsing remitting (RR) MS patients that underwent
      monthly gadolinium diethylentriaminepenta acid (Gd-DTPA) magnetic resonance
      imaging (MRI), the relation between serum MRP8/14 levels and disease activity was
      investigated. Patients were participating in a monoclonal antibody study
      targeting a specific T cell population (Vbeta5.2/5.3+ T-cells). In time, within
      patients large variations in serum MRP8/14 levels were observed. Serum MRP8/14
      levels were not related to changes in clinical disease activity or increase in Gd
      DTPA lesion enhancement. Neither did comparison of active (>1 relapse in follow
      up period) with inactive (0-1 relapse) MS patients reveal any differences in
      MRP8/14 levels. Therefore, we conclude that although MRP8/14 expression is a good
      histopathological marker for monocyte activation, serum levels of these proteins
      do not correlate with disease activity in RR MS.

PMID- 14975599
TI  - Histocompatibility antigens, aspirin use and cognitive performance in non
      demented elderly subjects.
AB  - HLA genotype and anti-inflammatory drug use have independently been associated
      with a lower risk of Alzheimer's disease (AD). We recently reported a negative
      association between aspirin use and AD. To investigate this further, we performed
      a cross-sectional study to investigate cognitive performance in 151 non-demented
      individuals in relation to HLA-DRB1 genotype and aspirin use. Aspirin and HLA
      DRB1*01 were positive predictors of performance on logical memory (aspirin,
      p=0.04) and verbal fluency tests (HLA-DRB1*01, p=0.018), respectively. HLA
      DRB1*05 had a negative impact on the Boston naming test (p=0.002). Our results
      suggest that aspirin use and inflammatory genotype may influence cognition in non
      demented subjects.

PMID- 14975600
TI  - The autoimmune T and B cell repertoires in monozygotic twins discordant for
      myasthenia gravis.
AB  - Two pairs of monozygotic twins, discordant for myasthenia gravis (MG) for more
      than 30 years, were studied regarding T cell and antibody reactivity against
      disease related autoantigens, the acetylcholine receptor, one idiotypic and one
      anti-idiotypic human monoclonal antibody. The healthy and myasthenic twins had
      very similar autoantibody repertoires. IgG fractions from both healthy and
      myasthenic twins had the same capacity to decrease the free acetylcholine
      receptor content in mice after passive transfer. In comparison with their
      myasthenic sisters, the healthy twins had lower T cell responses against the
      acetylcholine receptor.

PMID- 14975601
TI  - Immunomonitoring measures in relapsing-remitting multiple sclerosis.
AB  - Forty-five patients with relapsing-remitting multiple sclerosis (MS) were
      examined to determine intracellular cytokine profiles and the surface phenotype
      of circulating lymphocytes during active, recovery, and stable stages. Active
      stage patients were characterized by decreases in CD4(+)IL-4(+) Th2 as well as
      CD4(+)IFN-gamma(+) Th1 cells, when compared with stable stage patients and 16
      healthy controls. CCR4(+) Th2 cells were persistently decreased at every MS stage
      as compared to the controls. CD4(+)CD29(+) and CD4(+)CXCR3(+) cells were closely
      correlated with IFN-gamma-producing cells. These findings suggest that
      simultaneous flow cytometry for these two types of measurements can provide
      information concerning current immune status in MS.

PMID- 14975602
TI  - Usefulness of anti-GQ1b IgG antibody testing in Fisher syndrome compared with
      cerebrospinal fluid examination.
AB  - Fisher syndrome (FS), a variant of Guillain-Barre syndrome (GBS), is a rare
      disorder, and there are few reported studies of a large number of patients with
      FS. Cerebrospinal fluid (CSF) albuminocytological dissociation was found in 59%
      of 123 FS patients during the first 3 weeks of illness, while serum anti-GQ1b IgG
      antibody was positive in 85%. Whereas the incidence of CSF albuminocytological
      dissociation increased from the first to second weeks in FS, anti-GQ1b IgG
      antibody peaked in the first week, but there was no CSF albuminocytological
      dissociation. Statistically, anti-GQ1b antibody testing was superior to a CSF
      examination in supporting a diagnosis of FS during the first 3 weeks of illness,
      especially in the first week.

PMID- 14975603
TI  - Beneficial effect of interferon-beta 1b treatment in patients with relapsing
      remitting multiple sclerosis is associated with an increase in serum levels of
      soluble HLA-I molecules during the first 3 months of therapy.
AB  - It has recently become clear that interferon-beta (IFN-beta) treatment is
      effective in ameliorating relapsing-remitting multiple sclerosis (RRMS) through
      an as yet unidentified mechanism. As there is no recognisable biological
      indicator to predict responsiveness to IFN-beta treatment, we have investigated
      fluctuations in serum sHLA-I levels in MS patients undergoing IFN-beta 1b
      therapy. Serum sHLA-I concentrations measured by enzyme-linked immunosorbent
      assay (ELISA) were assessed at baseline and, longitudinally, over a period of 18
      months after the start of treatment in 29 RRMS patients grouped as responders and
      nonresponders according to their clinical response to IFN-beta 1b therapy. Thirty
      nine healthy volunteers served as controls. Serum sHLA-I concentrations were
      significantly higher (p<0.001) in pretreated RRMS patients than in healthy
      donors. In MS patients, changes in mean serum levels of sHLA-I from baseline
      showed a temporal pattern characterized by a strong increase in the first
      trimester of treatment, a return toward basal values in the following 6 months, a
      slight decline at 12th and 15th months and a further moderate increase at the
      18th month. Mean serum sHLA-I levels were significantly more elevated in
      responders than in nonresponders at the first (p<0.02), second (p<0.01), and at
      third (p<0.02) months after the beginning of treatment and significantly lower
      (p<0.01) at the time of relapses in comparison to baseline values. Overall, these
      results seem to indicate that IFN-beta 1b can modulate fluctuations in serum sHLA
      I levels and argue in favour of a potential role for serum levels of sHLA-I as a
      sensitive marker to monitor response to IFN-beta treatment in MS.

PMID- 14975604
TI  - Effects of the multiple sclerosis associated -330 promoter polymorphism in IL2
      allelic expression.
AB  - The -330 IL2 gene promoter polymorphism has been associated with multiple
      sclerosis (MS) [J. Neuroimmunol. 119 (2001) 101], but the basis underlying this
      association remains unknown to date. In the present work, we have found that IL2
      promoter-luciferase constructs, transfected in Jurkat cell line, showed twofold
      higher levels of gene expression in the -330 G allele. However, the
      transcriptional effect of this polymorphism in lymphocytes showed that the G
      allele was related to lower expression of IL2. This difference increased in the
      patient group. Divergence between in vivo and in vitro influence of the -330 IL2
      promoter polymorphic site suggests the existence of additional unknown
      polymorphisms affecting gene regulation. Our data show an increased IL2
      expression among GT and TT genotypes previously associated with susceptibility to
      MS.

PMID- 14975605
TI  - Association of common T cell activation gene polymorphisms with multiple
      sclerosis in Australian patients.
AB  - Susceptibility to multiple sclerosis (MS) may be influenced by the interaction of
      several genes within a biological pathway. T cell activation and costimulation
      may be potentially important in MS pathogenesis. We have therefore investigated
      associations between MS and polymorphisms in the CD152 (CTLA-4), CD28, CD80 and
      CD86 genes in Australian patients. We found no significant MS association with
      CTLA-4 exon 1 +49 alleles, and meta-analysis showed no significant association
      across nine comparable datasets (OR=1.04, p=0.54), nor with primary progressive
      MS across seven datasets (OR=1.19, p=0.21). Haplotype analysis showed a trend
      towards a decrease of the CTLA-4-1722C, -1577G, +49G haplotype in +49 G positive
      MS patients compared with controls (p=0.06). Screening of CD28, CD80 and CD86
      genes identified novel polymorphisms in the putative promoter regions of CD28 (
      372 G/A) and CD86 (exon 2 -359 deletionAAG). There was a significant increase of
      the CD28 -372 G allele frequency in MS patients vs. controls (p=0.045) and a
      trend towards a significant interaction between this allele and the CTLA-4 +49 G
      allele (OR=4.00, p=0.058). Our results suggest that the CTLA-4 +49 alone is not
      associated with overall susceptibility to MS, but may be important in clinical
      subsets of patients and/or may interact epistatically with other gene
      polymorphisms.

PMID- 14975606
TI  - Keeping ideology and bureaucracy out of science.

PMID- 14975607
TI  - Prolonged hospital stay after acute myocardial infarction: assessing the
      evidence.

PMID- 14975608
TI  - Sex, alloimmunisation, and susceptibility to HIV infection.

PMID- 14975609
TI  - Primary biliary cirrhosis: for want of an X chromosome?

PMID- 14975610
TI  - Butter-fingers.

PMID- 14975611
TI  - Telomere length and possible link to X chromosome.
AB  - BACKGROUND: Because telomeres are eroded during mitosis, telomere length
      indicates the replicative history of human somatic cells. Clinical markers of
      ageing--such as pulse pressure and survival--are associated with telomere length.
      On the basis of findings of studies in twins, telomere length seems to be
      familial, but little is known about its mode of inheritance. We aimed to
      investigate the inheritance of telomere length. METHODS: We measured terminal
      restriction fragment (TRF) length in white-blood-cell DNA taken from individuals
      from the family-based cohort of the Flemish Study on Environment, Genes, and
      Health Outcomes. FINDINGS: We recorded no correlation in sex and age adjusted TRF
      length between spouses (r=-0.05; p=0.70) nor between fathers and sons (r=-0.16;
      p=0.35). By contrast, we noted robust correlations in TRF length between fathers
      and daughters (r=0.60; p<0.0001); between mothers and sons (r=0.41; p=0.0017) and
      daughters (r=0.59; p<0.0001); and among siblings (r> or =0.61; p< or =0.0004).
      INTERPRETATION: X-linked inheritance of TRF length is the most probable
      explanation for our findings. Pending confirmation, our observations suggest that
      the process of ageing might be an X-linked trait.

PMID- 14975612
TI  - International differences in evolution of early discharge after acute myocardial
      infarction.
AB  - BACKGROUND: Early discharge of low-risk patients with acute myocardial infarction
      is feasible and can be achieved at no additional risk of adverse events. We aimed
      to identify the extent to which countries have taken advantage of the opportunity
      for early discharge. METHODS: The study population consisted of 54174 patients
      enrolled in GUSTO-I, GUSTO-III, and ASSENT-2 studies (enrollment period 1990-98)
      in the USA, Canada, Australia, New Zealand, Belgium, France, Germany, Spain, and
      Poland. We identified patients with uncomplicated acute myocardial infarction who
      were eligible for early discharge on the basis of previously established
      criteria, and assessed the extent to which these patients were discharged early-
      defined as discharged alive within 4 days of admission. The economic consequences
      (defined as potentially unnecessary hospital days consumed per 100 patients
      enrolled) were also investigated. FINDINGS: Patients in all European countries
      had significantly longer stays than did those from non-European countries. Over
      the study period, the number of eligible patients discharged on or before day 4
      increased in the USA, Canada, Australia, and New Zealand. Despite this increase,
      no more than 40% of patients who were eligible for early discharge were actually
      discharged early. The rate of early discharge of eligible patients was
      consistently low (<2%) in Belgium, France, Germany, Spain, and Poland. In ASSENT
      2, which is the most recent trial in this study, the number of potentially
      unnecessary hospital days (per 100 patients enrolled) ranged from 65 in New
      Zealand to 839 in Germany. INTERPRETATION: Despite more than a decade of
      research, there is still a lot of variation between countries in international
      length-of-stay patterns in acute myocardial infarction. The potential for more
      efficient discharge of low-risk patients exists in all countries investigated,
      but was especially evident in the European countries included in the study
      (Belgium, France, Germany, Spain, and Poland).

PMID- 14975613
TI  - Migraine prodrome: a nose on a face.

PMID- 14975614
TI  - Effect of heterosexual intercourse on mucosal alloimmunisation and resistance to
      HIV-1 infection.
AB  - BACKGROUND: Unprotected sexual intercourse between regular heterosexual partners
      could elicit alloimmune responses that might be associated with inhibition of in
      vitro HIV-1 infectivity. We investigated this hypothesis in people practising
      unprotected sex and those using protection. METHODS: We recruited 82 participants
      from an outpatient genitourinary medicine clinic. 29 monogamous heterosexual
      couples having unprotected sex; and 15 women and 10 men having condom protected
      or no sex. We used the mixed leucocyte reaction (MLR), stimulating one partner's
      peripheral blood mononuclear cells (PBMC) with the other partner's irradiated
      PBMC and compared the resulting response with control PBMC. We studied resistance
      to HIV-1 infection by challenging activated CD4-positive T cells with CCR5
      binding and CXCR4-binding HIV-1 strains, and comparing the infectivity in
      participants having unprotected sex with those practising protected sex. We used
      the correlation coefficient to establish the significance of the relation between
      MLR and HIV-1 infectivity. FINDINGS: We recorded a significant increase in the
      stimulation indices in PBMC from women whose cells were stimulated with
      irradiated PBMC (2%, 10%, or 50%) from their regular partners. The mean with 10%
      partner's cells was 8.6 (SD 7.7), compared with those from unrelated cells (4.7
      [3.9], p=0.009). Significant alloimmune responses were also seen in corresponding
      male partners, but only with 50% stimulating cells (p=0.013). Dose-dependent
      inhibition of activated CD4-positive T cells to HIV-1 infection with both binding
      strains was noted in vitro in women practising unprotected intercourse, compared
      with those having protected sex or having no sex for more than 1 year. Highly
      significant differences were found for CCR5 (p=0.0001) and for CXCR4 (p=0.001)
      strains of HIV-1 at all four virus-concentrations. Male partners also showed in
      vitro inhibition of HIV-1 but this was less than that in women. INTERPRETATION:
      Unprotected sexual intercourse might result in alloimmunisation stimulated by HLA
      antigens in seminal or cervicovaginal fluid. Mucosal alloimmunisation may reduce
      infection by HIV-1, and the role of such immunisation in preventive and
      therapeutic vaccination should be investigated.

PMID- 14975615
TI  - Castleman's tumours and production of autoantibody in paraneoplastic pemphigus.
AB  - BACKGROUND: Paraneoplastic pemphigus is an autoimmune mucocutaneous disease
      associated with Castleman's tumours, which when surgically removed often result
      in great improvement of mucocutaneous lesions. An IgG autoantibody against
      epidermal proteins is often used as a diagnostic marker for disease. Our aim was
      to ascertain the role of Castleman's tumours in production of the autoantibody
      and pathogenesis of paraneoplastic pemphigus. METHODS: We enrolled seven patients
      with paraneoplastic pemphigus associated with Castleman's disease and assessed
      the effect of removal of tumours on mucocutaneous lesions in six individuals and
      on autoantibody titre with indirect immunofluorescence in four patients. We
      cultured tumour cells from one patient and assayed the secreted autoantibody.
      Finally, we characterised the gene sequence and expression of the variable region
      of the immunoglobulin heavy chain (IgV(H)) in tumour B cells from all patients by
      reverse transcription-PCR, DNA sequencing, and in-situ hybridisation. FINDINGS:
      Cutaneous lesions disappeared within 6-11 weeks after resection of tumours.
      Mucosal lesions also improved in this period, but lasted for 5-10 months overall.
      Autoantibody titre decreased and became undetectable within 5-9 weeks in three of
      four patients assessed. We identified secreted autoantibody, similar to that
      identified in patients' serum, in cultured tumour cells. The tumour B-cells of
      the seven patients shared and expressed two rearrangement patterns of
      complementarity determining region 3 (CDR3) of IgV(H). INTERPRETATION: Secreted
      autoantibody from Castleman's tumours, which reacts against epidermal proteins,
      could be an essential factor in the pathogenesis of paraneoplastic pemphigus. We
      noted clonal rearrangement, resulting in similar variable regions of IgV(H), in
      tumour B cells isolated from all seven patients. However, whether this pattern is
      associated with autoimmunity remains to be ascertained.

PMID- 14975616
TI  - A silver man.

PMID- 14975617
TI  - Frequency of monosomy X in women with primary biliary cirrhosis.
AB  - The mechanisms that cause the female predominance of primary biliary cirrhosis
      (PBC) are uncertain, but the X chromosome includes genes involved in
      immunological tolerance. We assessed the rate of X monosomy in peripheral white
      blood cells from 100 women with PBC, 50 with chronic hepatitis C, and 50 healthy
      controls, by fluorescence in-situ hybridisation. Frequency of X monosomy
      increased with age in all groups, but was significantly higher in women with PBC
      than in controls (p<0.0001); age-adjusted back-transformed mean frequencies were
      0.050 (95% CI 0.046-0.055) in women with PBC, 0.032 (0.028-0.036) in those with
      chronic hepatitis C, and 0.028 (0.025-0.032) in controls. We suggest that
      haploinsufficiency for specific X-linked genes leads to female susceptibility to
      PBC.

PMID- 14975618
TI  - Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell
      acute lymphoblastic leukaemia.
AB  - The activation of oncogenic transcription factors defines distinct molecular
      subsets of T-cell acute lymphoblastic leukaemia and has prognostic relevance in
      children. We investigated the prognostic effect of the expression levels of eight
      oncogenic transcription factors--TLX1 (HOX11), TLX3 (HOX11L2), TAL1, TAL2, LYL1,
      OLIG2 (BHLHB1), LMO1, and LMO2--in 52 adults with T-cell acute lymphoblastic
      leukaemia. The leukaemia-specific survival rate for the 16 TLX1-positive patients
      was 88% (90% CI 73-100%), compared with 56% (42-70%) for all other cases
      (p=0.019). Only the TLX1 oncogene expression subgroup showed difference in
      leukaemia-specific survival. Our results suggest that overexpression of TLX1
      confers a good outlook for adults with T-cell acute lymphoblastic leukaemia.
      Furthermore, our findings lead to questions about whether stem-cell
      transplantation in first remission is necessary for effective treatment of
      patients in the low-risk subgroup of patients with TLX1 oncogene expression.

PMID- 14975619
TI  - Sexually transmissible infections other than HIV.
AB  - Sexually transmitted infections (STIs) are notable for their fastidious
      requirements for transmission and growth in the laboratory and for their high
      physical and psychosocial morbidity. The combination of subtle or absent symptoms
      and stigma preventing the seeking of health care, leaves many infections
      undiagnosed. The development of nucleic-acid amplification tests heralded a new
      era in sensitive and robust diagnostic procedures for STIs. Unfortunately, many
      of these tests are not commercially available or are too expensive for the
      populations that need them most. Single-dose oral azithromycin has improved the
      treatment of several bacterial STIs, but quinolones are rapidly becoming
      ineffective for gonorrhoea. Self-treatment of genital warts with podophyllotoxin
      or imiquimod preparations is attractive to patients and might be cost effective
      for health services. The prospect of effective vaccines against genital
      papillomaviruses in the near future is real. Such vaccines could reduce the
      global incidence of some anogenital cancers. Episodic treatment of genital herpes
      is getting easier and cheaper, and suppressive treatment can reduce transmission
      to regular sexual partners. A vaccine against herpes simplex virus type 2 has
      shown some limited efficacy. Ultimately, better control of STIs, and reduction of
      their contribution to the spread of HIV, will require a broad health-sector
      response with adequate resourcing, and a change in social and political
      attitudes.

PMID- 14975620
TI  - The role of civil society in protecting public health over commercial interests:
      lessons from Thailand.

PMID- 14975621
TI  - Distortions and difficulties in data for trafficking.

PMID- 14975622
TI  - MMR and autism: the debate continues.

PMID- 14975624
TI  - MMR and autism: the debate continues.

PMID- 14975625
TI  - MMR and autism: the debate continues.

PMID- 14975626
TI  - MMR immunisation after contact with measles virus.

PMID- 14975627
TI  - Effect of HAART on liver-related mortality in patients with HIV/HCV coinfection.

PMID- 14975628
TI  - Effect of HAART on liver-related mortality in patients with HIV/HCV coinfection.

PMID- 14975631
TI  - Coronary risk scores.

PMID- 14975632
TI  - Epilepsy and manganese.

PMID- 14975633
TI  - Relevant research for health-systems management and policy.

PMID- 14975634
TI  - Developing healthy public policy in Nigeria.

PMID- 14975635
TI  - Vitamin D supplementation in pregnancy.

PMID- 14975636
TI  - The versatile lymphocyte count.

PMID- 14975637
TI  - Rosemary Edwards.

PMID- 14975638
TI  - What a gummer!

PMID- 14975639
TI  - Paul B Spiegel. Interview.

PMID- 14975640
TI  - Physico-chemical factors affecting the E. coli removal in a rotating biological
      contactor (RBC) treating UASB effluent.
AB  - The removal mechanism of E. coli from UASB effluent using a Rotating Biological
      Contractor (RBC) has been investigated. Preliminary batch experiments in a RBC
      indicate a first-order removal kinetics. Variation in the dissolved oxygen
      concentration and E. coli counts over the depth of the RBC has been recorded and
      indicates that the RBC is not a completely mixed reactor. Therefore batch
      experiments were carried out in a beaker where the different operating conditions
      can be controlled. Factors affecting the removal of E. coli via a biofilm system
      as stirring, dissolved oxygen concentration, pH, and addition of cationic polymer
      were investigated. The results obtained indicated that the most important removal
      mechanism of E. coli in the biofilm is the adsorption process, followed by
      sedimentation. Die-off is a relatively minor removal mechanism in an RBC system.
      Higher removal rate of E. coli was observed in an aerobic compared to an
      anaerobic biofilm system. Variation of dissolved oxygen concentration (3.3-8.7
      mgl(-1)) and pH-values between 6.5 and 9.3 did not exert any significant effect
      on the removal rate of the E. coli by the heterotrophic biofilm. A rapid
      adsorption of E. coli to the biofilm occurred during the first days after adding
      the cationic polymer, after which the adsorption slowed down.

PMID- 14975641
TI  - Reaeration in sewers.
AB  - The sewer system is a very dynamic system with an abundance of mass transfer
      processes and transformations. A key process is the mass exchange between the
      wastewater and the sewer atmosphere. An equation that describes the gas-liquid
      mass transfer under different hydrodynamic conditions is essential when sewer
      processes are to be quantified or modelled. In this work, a calibrated reaeration
      equation is proposed. It is based on the shear Reynolds and the Froude number to
      correct the increased gas-liquid interface roughness to higher flow rates. The
      equation was calibrated with previously published data and with new data. This
      data was obtained with a safe and environmentally friendly gas tracer method for
      gravity sewers based on the inert gas sulphur hexafluoride (SF6), a new method
      for the sewer system. Measurements were conducted in four channels under
      different conditions. The resulting equation will allow for more accurate
      simulations of the sewer system. Finally, the effect of reaeration with regard to
      the oxygen consuming processes for different hydrodynamic conditions is
      discussed.

PMID- 14975642
TI  - Sampling and quantifying invertebrates from drinking water distribution mains.
AB  - Water utilities in the Netherlands aim at controlling the multiplication of
      (micro-) organisms by distributing biologically stable water through biologically
      stable materials. Disinfectant residuals are absent or very low. To be able to
      assess invertebrate abundance, methods for sampling and quantifying these animals
      from distribution mains were optimised and evaluated. The presented method for
      collecting invertebrates consists of unidirectionally flushing a mains section
      with a flow rate of 1 ms(-1) and filtering the flushed water in two separate
      flows with 500 microm and 100 microm mesh plankton gauze filters. Removal
      efficiency from mains was evaluated in nine experiments by collecting the
      invertebrates removed from the mains section by intensive cleaning immediately
      subsequent to sampling. Of 12 taxa distinguished, all except case-building
      Chironomidae larvae (2%) and Oligochaeta (30%) were removed well (51-75%).
      Retention of invertebrates in 100 microm filters was evaluated by filtering 39
      filtrates using 30 microm filters. Except for flexible and small invertebrates
      such as Turbellaria (13%), Nematoda (11%) and Copepoda larvae (24%), most taxa
      were well retained in the 100 microm filters (53-100%). During sample processing,
      the method for taking sub-samples with a 10 ml pipette from the suspension of
      samples with high sediment concentrations was found to perform well in 75% of the
      samples. During a 2-year national survey in the Netherlands and consecutive
      investigations, the method appeared to be very suitable to assess the abundance
      of most invertebrate taxa in drinking water distribution systems and to be
      practicable for relatively inexperienced sampling and lab technicians. Although
      the numbers of small, less abundant or sessile taxa were not accurately assessed
      using the method, these taxa probably should not be the primary focus of
      monitoring by water utilities, as consumer complaints are not likely to be caused
      by these invertebrates. The accuracy of quantifying small invertebrates was
      further improved, however, by filtering the 100microm filtrate with a 30microm
      mesh plankton gauze filter.

PMID- 14975643
TI  - Die-off of enteric bacterial pathogens during mesophilic anaerobic digestion.
AB  - Conventionally treated sewage sludge may contain high concentrations of
      potentially pathogenic microorganisms and additional treatment is required to
      minimise the risks to health if it is to be recycled to agricultural land.
      Mesophilic anaerobic digestion (MAD) is the most widely used process in the UK
      for stabilising sludge prior to agricultural recycling, but little is known about
      the fate of a number of enteric pathogens as the sludge passes through the
      treatment processes. The aim of this study was to determine the efficiency of MAD
      in removing the bacterial enteric pathogens, Salmonella senftenberg, Listeria
      monocytogenes and Campylobacter jejuni which were added as a spike to the
      digester feedstock, together with the die-off of indigenous Escherichia coli
      already present in the sludge. The primary sludge digestion stage of MAD was
      found to achieve a log removal of 1.66 for E. coli, 2.23 for L. monocytogenes and
      2.23 for S. senftenberg. However, the extent of die-off was a function of the
      numbers of pathogens in the feed and as these increased the log removal also
      increased. The numbers of C. jejuni were not affected by primary sludge
      digestion. Additional die-off was provided by secondary sludge digestion with log
      removals of 1.70 for E. coli, 2.10 for S. senftenberg and 0.36 for C. jejuni.

PMID- 14975644
TI  - Mobilization of adsorbed copper and lead from naturally aged soil by bacterial
      extracellular polymers.
AB  - Sorption of pollutants is a dominant phase transfer process affecting the fate
      and transport of metals through the subsurface. The movement of contaminants is
      retarded by sorption to the stationary subsurface porous media and can seriously
      hinder remediation efforts. Research has shown that the binding of adsorbed
      metals becomes more pronounced the longer the contaminant is in the subsurface
      and the release rates of aged metal contaminants have not received the research
      attention given to freshly added metals in laboratory studies. Metal release
      rates are also influenced by the presence of dissolved ligands that compete with
      mineral soil surfaces by providing binding sites. Dissolved organic matter such
      as bacterial extracellular polymers are common in natural soil solutions and the
      metal binding properties of bacterial polymers are well established. Therefore,
      binding of metals to dissolved biopolymers may result in mobilization of an
      adsorbed metal. This is important for cases where the metals are assumed to be
      relatively immobile such as in the case of land applied biosolids. In addition,
      naturally occurring adherent bacteria commonly produce extracellular polymers and
      thus may modify the bioavailability of meal contaminants at the point of their
      attachment. In this study samples from three sites, one a land applied sludge
      test site, were used to investigate the ability of bacterial extracellular
      polymers to release metals from soils with long-term exposures. The presence of
      ?200mg/L bacterial extracellular polymer was found to increase the short-term
      (less than 350h) release of Cu and Pb by a factor of 2-4-fold.

PMID- 14975645
TI  - Nature of ammonium ion adsorption by sepiolite: analysis of equilibrium data with
      several isotherms.
AB  - Adsorption isotherms for an ammonium ion-sepiolite system have been established
      for initial ammonium ion solution concentrations in the range of 8.32-388.06 mmol
      NH(4)(+)/L (150-7000 ppm). The change of the "g sepiolite/mL solution" ratios
      from 1/10 to 1/70 caused an increase in the adsorption from 1.82 to 3.70 mmol
      NH(4)(+)/g for the average particle size of 2.8mm. The equilibrium data were
      fitted to "general-purpose isotherms" and "first-order adsorption model", and the
      adjustable parameters of the isotherms were estimated by nonlinear least-squares
      analysis. Langmuir and Freundlich models were found insufficient to explain the
      adsorption equilibrium, while Langmuir-Freundlich and Tooth isotherms explained
      the data well. Goodness of fit increased with the increased sepiolite quantity in
      the treated suspension.

PMID- 14975646
TI  - Study on characteristics of biocometabolic removal of omethoate by the
      Aspergillus spp.
AB  - A strain Aspergillus spp. F1 which could effectively metabolized omethoate was
      screened out in this study. F1 tended to form granula with diameter 4-5mm after 5
      days culture in shaker. The pH range from 4.5 to 6.5 was the suitable pH range
      for growth and metabolism of Aspergillus spp. F1. The maximum omethoate removal
      rate was about 3.0mg/(hL), and the removal fraction of omethoate reached 90%
      after 8 days culture when initial concentrations of omethoate were not more than
      2000mg/L in medium. There was no obvious relativity between cell growth and
      cometabolism of omethoate. Starch was the best carbon source for omethoate
      removal and the result after 3 days reached 56.6% removal. F1 could use omethoate
      to metabolize as single nitrogen or phosphate source. The residual fragments in
      medium after treatment with the Aspergillus spp. F1 were determined by gas
      chromatography-mass spectrometry. The analysis results showed that only fragment
      o,o,s,-trimethyl phosphorothioate (TEP) containing phosphorus was available and
      the fragment containing nitrogen was consumed by F1 thoroughly in culture
      process. But no accumulations of TEP were observed in the omethoate
      bioremediation process. F1 could effectively remove omethoate in complex
      nutritional environment safely.

PMID- 14975647
TI  - Solar photocatalytic treatment of synthetic municipal wastewater.
AB  - The photocatalytic organic content reduction of a selected synthetic municipal
      wastewater by the use of heterogeneous and homogeneous photocatalytic methods
      under solar irradiation has been studied at a pilot-plant scale at the Plataforma
      Solar de Almeria. In the case of heterogeneous photocatalysis the effect of
      catalysts and oxidants concentration on the decomposition degree of the
      wastewater was examined. By an accumulation energy of 50 kJL(-1) the synergetic
      effect of 0.2 gL(-1)TiO(2) P-25 with hydrogen peroxide (H(2)O(2)) and
      Na(2)S(2)O(8) leads to a 55% and 73% reduction of the initial organic carbon
      content, respectively. The photo-fenton process appears to be more efficient for
      this type of wastewater in comparison to the TiO(2)/oxidant system. An
      accumulation energy of 20 kJL(-1) leads to 80% reduction of the organic content.
      The presence of oxalate in the Fe(3+)/H(2)O(2) system leads to an additional
      improvement of the photocatalytic efficiency.

PMID- 14975648
TI  - Arsenic-sulfides confound anion exchange resin speciation of aqueous arsenic.
AB  - A field-portable anion exchange resin method (often cited as the Ficklin method
      (1983)) has been extensively used to distinguish between dissolved arsenite
      (As(III)) and arsenate (As(V)) species in natural waters. As(III) occurs largely
      as As(OH)(3), which is uncharged at ca. pH 7, while As(V) is negatively charged
      and will sorb to the resin. However, we show that negatively charged As(III)
      sulfide (thioarsenite) species, important at sulfide concentrations >10 microM,
      also bind to the anion exchange resins, and therefore might be interpreted
      incorrectly as As(V). Furthermore, we show that nitrogen-purging, which results
      in a conversion of As(III)-sulfides to arsenite, can be used to obtain accurate
      arsenic speciation when resins are used on sulfidic water samples.

PMID- 14975649
TI  - Nitrogen control in AO process with recirculation of solubilized excess sludge.
AB  - In order to establish a sludgeless process with a nitrogen-controlled effluent,
      batch and continuous experiments in a lab scale anoxic-oxic (AO) process were
      carried out to investigate the possibility of ozonized sludge (OS) usage as a
      denitrification energy source. Through ozonation at an ozone dose of 1.2g O(3)/g
      MLVSS, 63.2% of treated MLVSS was solubilized, 12.7% of COD was lost (probably
      due to complete oxidation to CO(2)), and soluble COD/TN ratio of OS appeared to
      be only about 10.78 because ozonation released cellular proteins and other
      nitrogenous substances. In oxic conditions, incubation of OS supernatant with
      activated sludge generated nitrate without significant ammonia accumulation,
      which meant that rapid nitrification occurred following ammonia generation from
      heterotrophic degradation of nitrogen-bearing cellular substances. In anoxic
      conditions, externally supplied nitrate was removed at the expense of organic
      carbons in the OS supernatant. However, ammonia was accumulated as anoxic
      incubation proceeded probably because of heterotrophic degradation of nitrogenous
      materials as in oxic conditions. Thus it was appeared that solubilized excess
      sludge acted as a reducing power for denitrification but also as a nitrogen
      source. In addition, 24-41% of COD contained in OS supernatant were found to be
      consumed for denitrification. But the remaining COD was not assimilated further
      even in the presence of nitrate. It was concluded by a nitrogen balance analysis
      that the energy source contained in OS was not sufficient to completely reduce
      the nitrogen that was originated from OS itself to nitrogen gas.

PMID- 14975650
TI  - Treatment of drinking water residuals: comparing sedimentation and dissolved air
      flotation performance with optimal cation ratios.
AB  - Spent filter backwash water (SFBW) and clarifier sludge generally comprise the
      majority of the waste residual volume generated and in relative terms, these can
      be collectively referred to as combined filter backwash water (CFBW). CFBW is
      essentially a low-solids wastewater with metal hydroxide flocs that are typically
      light and slow to settle. This study evaluates the impact of adding calcium and
      magnesium carbonates to CFBW in terms of assessing the impacts on the
      sedimentation and DAF separation processes. Representative CFBW samples were
      collected from two surface water treatment plants (WTP): Lake Major WTP
      (Dartmouth, Nova Scotia, Canada) and Victoria Park WTP (Truro, Nova Scotia,
      Canada). Bench-scale results indicated that improvements in the CFBW settled
      water quality could be achieved through the addition of the divalent cations,
      thereby adjusting the monovalent to divalent (M:D) ratios of the wastewater. In
      general, the DAF process required slightly higher M:D ratios than the
      sedimentation process. The optimum M:D ratios for DAF and sedimentation were
      determined to be 1:1 and 0.33:1, respectively. It was concluded that the
      optimisation of the cation balance between monovalent cations (e.g., Na(+), K(+))
      and added divalent cations (i.e., Ca(2+), Mg(2+)) aided in the settling mechanism
      through charge neutralisation-precipitation. The increase in divalent cation
      concentrations within the waste residual stream promoted destabilisation of the
      negatively charged colour molecules within the CFBW, thereby causing the
      colloidal content to become more hydrophobic.

PMID- 14975651
TI  - Comparison of bacterial indicator analysis methods in stormwater-affected coastal
      waters.
AB  - Membrane filtration (MF) and multiple tube fermentation (MTF) have been used for
      decades to measure indicator bacteria levels in beach water samples, but new
      methods based on chromogenic substrate (CS) technology are becoming increasingly
      popular. Only a few studies have compared results among these methods and they
      have generally been based on samples collected from a limited number of sites
      during dry weather. In this study, samples were collected from 108 sites the day
      after a major rainstorm, and three indicator bacteria (total coliforms (TCs),
      fecal coliforms (FCs) or E. coli, and enterococci (EC)) were each measured using
      MF, MTF, and CS. Sampling sites were selected using a stratified random design,
      stratified by open sandy beach, rocky shoreline, and beach areas near urban
      runoff outlets. The CS results were found to be highly correlated with both MF
      and MTF for all three indicators regardless of whether the samples were taken
      along open shoreline or near a runoff outlet. While correlated, TC values were
      higher using the CS method, consistent with other studies that have demonstrated
      false positives with this method. FC values were 12% lower with CS, reflecting
      the specificity of the CS method for E. coli rather than for the entire FC group.
      No significant differences were observed for EC, although some differences were
      observed within specific laboratories. Differences for all of these indicators
      were small enough that, when assessed categorically, there was more than 90%
      agreement between CS methods and either MF or MTF methods as to whether State of
      California Beach Water Quality Standards were met or exceeded.

PMID- 14975652
TI  - Investigation of biocide efficacy by photoacoustic biofilm monitoring.
AB  - The undesired growth of biofilms on solid surfaces is often termed biofouling.
      Biofilms consist mainly of water and microbial cells which are embedded in a
      biopolymer matrix. Biofouling lowers the water quality and increases the
      frictional resistance in tubes. Further, biofilms increase the pressure
      differences in membrane processes and can clog filtration membranes, valves, and
      nozzles. For investigation and improvement of biocide efficacy and anti-fouling
      strategies, on-line and in situ monitoring of the biofilm is necessary. In this
      study, photoacoustic spectroscopy (PAS) was employed for biofilm monitoring. PAS
      allows the depth-resolved investigation of growth and detachment processes of
      biofilms. Strategies based on the oxidant hydrogen peroxide were compared to
      popular isothiazolinone biocides. Hydrogen peroxide allowed a very fast and
      efficient removal of attached biofilms, whereas no effect on the biofilm matrix
      was observed in most cases when isothiazolinone biocides were used.

PMID- 14975653
TI  - Investigation of natural biofilms formed during the production of drinking water
      from surface water embankment filtration.
AB  - Populations of bacteria in biofilms from different sites of a drinking water
      production system were analysed. Polymerase chain reaction (PCR) and denaturing
      gradient gel electrophoresis (DGGE) analyses revealed changing DNA band patterns,
      suggesting a population shift during bank filtration and processing at the
      waterworks. In addition, common DNA bands that were attributed to ubiquitous
      bacteria were found. Biofilms even developed directly after UV disinfection (1-2m
      distance). Their DNA band patterns only partly agreed with those of the biofilms
      from the downstream distribution system. Opportunistic pathogenic bacteria in
      biofilms were analysed using PCR and Southern blot hybridisation (SBH). Surface
      water appeared to have a direct influence on the composition of biofilms in the
      drinking water distribution system. In spite of preceding filtration and UV
      disinfection, opportunistic pathogens such as atypical mycobacteria and
      Legionella spp. were found in biofilms of drinking water, and Pseudomonas
      aeruginosa was detected sporadically. Enterococci were not found in any biofilm.
      Bacterial cell counts in the biofilms from surface water to drinking water
      dropped significantly, and esterase and alanine-aminopeptidase activity
      decreased. beta-glucosidase activity was not found in the biofilms. Contrary to
      the results for planktonic bacteria, inhibitory effects were not observed in
      biofilms. This suggested an increased tolerance of biofilm bacteria against toxic
      compounds.

PMID- 14975654
TI  - Effects of pH and competing anions on the speciation of arsenic in fixed ionic
      strength solutions by solid phase extraction cartridges.
AB  - Anion exchange resins (AERs) separate As(V) and As(III) in solution by retaining
      As(V) and allowing As(III) to pass through. Anion exchange resins offer several
      advantages including cost, portability, and ease of use. The use of AERs for the
      instantaneous speciation of As minimizes the effects of preservatives on As
      species analysis. The aims of this study were to: (1) Examine the effects of pH
      and competing anions on the efficacy of solid phase extraction cartridges (SPECs)
      for speciation of As in a 0.01 molL(-1) NaNO(3) background electrolyte. (2)
      Identify optimal conditions (e.g. flow rates) for As speciation. (3) Calculate
      method detection limits (MDLs) from spiked background electrolyte and percent
      recoveries of As species from spiked extracts of mine wastes. The most effective
      SPEC retained As(V) through a range of environmentally relevant pH values (4-8).
      The mass loading capacity for As(V) was reduced in the background electrolyte
      (0.006 mg) compared with As(V) in deionized H(2)O (0.75 mg). Some retention (10
      20%) of As(III) occurred on pre-wetted cartridges. Approximately 98% of spiked
      As(III) passed through dry cartridges. The recommended flow rate (0.5 mL min(-1))
      was increased to 5 mL min(-1) without significant effect on As(V) retention. The
      presence of anions decreased the retention of As(V) with sulfate and phosphate
      having the greatest impact. MDLs were 0.004 mg L(-1) for both inorganic species.
      Spike recoveries in 0.01 M NaNO(3) mine waste extracts averaged 94% for As(III)
      and 107% for As(V).

PMID- 14975655
TI  - Faecal bacteria yields in artificial flood events: quantifying in-stream stores.
AB  - Stream sediments have been recognised as an in-channel store of faecal
      contamination that can be mobilised during floods or other sediment-disturbing
      events. We studied this store of faecal contamination by creating artificial
      floods during dry weather when, in the absence of overland flow from the
      catchment, the only source of faecal bacteria was stores within the channel.
      Artificial floods, created by releasing water from a supply reservoir, increased
      the E. coli concentration in the water column by two orders of magnitude, from a
      background level of 10(2) cfu per 100 mL to over 10(4) cfu per 100 mL. The
      bacterial peak concentrations and yields declined systematically through a
      triplicate flood series. The size of the total in-channel store, calculated as
      the sum of yields of an infinite series of artificial floods, was approximately
      10(8) cfu m(-2) of streambed area. Direct measurements of sediment E. coli found
      few sites (only those associated with cattle crossings) with areal concentrations
      as high as 10(8) cfu m(-2), consistent with flood yields. Concentrations of E.
      coli in the biofilms on exposed rocks were orders of magnitude lower, indicating
      that exposed rocks were not a source of E. coli released by the artificial
      floods.

PMID- 14975656
TI  - Removal of benzoic acid in aqueous solution by Fe(III) homogeneous
      photocatalysis.
AB  - The behaviour of the system Fe(III)/Air/UV-benzoic acid is investigated in the pH
      range 2.0-5.5 and Fe(III) concentration up to 60 microM. The oxidation process
      develops through the establishment of an iron cycle in which HO radicals are
      produced by Fe(OH)2+ photolysis and the resulting Fe(II) photo-oxidized to
      Fe(III) by dissolved oxygen. A kinetic model is developed and used to simulate
      the behaviour of the system.

PMID- 14975657
TI  - Quantification of oxygen fluxes in a long gravity sewer.
AB  - Quantification of the oxygen fluxes in the sewer system is at present the optimal
      methodology to obtain information about the influence of sewers on
      transformations and mass balances in the urban drainage system. However, the
      relative and absolute values of these fluxes are practically unknown. In this
      work, the oxygen fluxes were quantified experimentally in a full-scale aerobic
      main sewer. The sewer biofilm respiration was determined with an in situ flow
      cell, a method that has not been used before in the sewer. The surface reaeration
      was determined with a gas tracer method based on the inert, non-radio-active and
      non-toxic gas tracer sulphur hexafluoride. In addition, the wastewater biomass
      respiration rate was measured. The validity of the applied methods was verified
      with redundant oxygen balances over a 2-km-long section. Measurement campaigns
      under different hydrodynamic conditions showed that the relative contribution of
      the biofilm, the wastewater, the reaeration and the in- and outflow with the
      water, all contributed significantly. However, the absolute contributions varied
      extensively and depended especially on the discharge. The COD conversion in the
      sewer could be estimated from the aerobic activity. The aerobic total degradation
      in the study reach was 3%. However, when extrapolated to the entire sewer net of
      the catchment area with 5000 PE, the COD conversion was estimated as high as 30%
      of the dissolved COD during the night. This indicates that the wastewater
      composition at the treatment plant will be strongly affected by the sewer system.

PMID- 14975658
TI  - Micro-profiles of activated sludge floc determined using microelectrodes.
AB  - The microbial activity within activated sludge floc is a key factor in the
      performance of the activated sludge process. In this study, the microenvironment
      of activated sludge flocs from two wastewater treatment plants (Mill Creek
      Wastewater Treatment Plant and Muddy Creek Wastewater Treatment Plant, with
      aeration tank influent CODs of 60-120 and 15-35 mg/L, respectively) were studied
      by using microelectrodes. Due to microbial oxygen utilization, the aerobic region
      in the activated sludge floc was limited to the surface layer (0.1-0.2mm) of the
      sludge aggregate at the Mill Creek plant. The presence of an anoxic zone inside
      the sludge floc under aerobic conditions was confirmed in this study. When the
      dissolved oxygen (DO) in the bulk liquid was higher than 4.0mg/L, the anoxic zone
      inside the activated sludge floc disappeared, which is helpful for
      biodegradation. At the Muddy Creek plant, with its lower wastewater pollutant
      concentrations, the redox potential and DO inside the sludge aggregates were
      higher than those at the Mill Creek plant. The contaminant concentration in the
      bulk wastewater correlates with the oxygen utilization rate, which directly
      influences the oxygen penetration inside the activated sludge floc, and results
      in redox potential changes within the floc. The measured microprofiles revealed
      the continuous decrease of nitrate concentration inside the activated sludge
      floc, even though significant nitrification was observed in the bulk wastewater.
      The oxygen consumption and nitrification rate analyses reveal that the increase
      of ammonia flux under aerobic conditions correlates with nitrification. Due to
      the metabolic mechanisms of the microorganisms in activated sludge floc, which
      varies from one treatment plant to another, the oxygen flux inside the sludge
      floc changes accordingly.

PMID- 14975659
TI  - Iron release from corroded iron pipes in drinking water distribution systems:
      effect of dissolved oxygen.
AB  - Iron release from corroded iron pipes is the principal cause of "colored water"
      problems in drinking water distribution systems. The corrosion scales present in
      corroded iron pipes restrict the flow of water, and can also deteriorate the
      water quality. This research was focused on understanding the effect of dissolved
      oxygen (DO), a key water quality parameter, on iron release from the old corroded
      iron pipes. Corrosion scales from 70-year-old galvanized iron pipe were
      characterized as porous deposits of Fe(III) phases (goethite (alpha-FeOOH),
      magnetite (Fe(3)O(4)), and maghemite (alpha-Fe(2)O(3))) with a shell-like, dense
      layer near the top of the scales. High concentrations of readily soluble Fe(II)
      content was present inside the scales. Iron release from these corroded pipes was
      investigated for both flow and stagnant water conditions. Our studies confirmed
      that iron was released to bulk water primarily in the ferrous form. When DO was
      present in water, higher amounts of iron release was observed during stagnation
      in comparison to flowing water conditions. Additionally, it was found that
      increasing the DO concentration in water during stagnation reduced the amount of
      iron release. Our studies substantiate that increasing the concentration of
      oxidants in water and maintaining flowing conditions can reduce the amount of
      iron release from corroded iron pipes. Based on our studies, it is proposed that
      iron is released from corroded iron pipes by dissolution of corrosion scales, and
      that the microstructure and composition of corrosion scales are important
      parameters that can influence the amount of iron released from such systems.

PMID- 14975660
TI  - (Un)certainty of overall binding constants of Al with dissolved organic matter
      determined by the Scatchard approach.
AB  - One of the best approaches to date to obtain overall binding constants (Ko) for
      Al and dissolved organic matter (DOM) from acidic soil solutions is to collect
      'free' Al data with diffusive gradients in thin films (DGT) and to infer the Ko
      values by fitting a continuous distribution model based on Scatchard plots.
      Although there is clear established literature demonstrating the usefulness of
      the Scatchard approach, relatively little attention has been given to a realistic
      assessment of the uncertainties associated with the final fitted Ko values. In
      this study we present an uncertainty analysis of the fitted Ko values using a
      synthetic dataset with different levels of random noise and a real data set using
      DGT data from an acidic soil solution. The parameters in the continuous
      distribution model and their corresponding upper and lower 95% uncertainty bounds
      were determined using the Shuffled Complex Evolution Metropolis (SCEM) algorithm.
      Although reasonable fits of the distribution model to the experimental data were
      obtained in all cases, an appreciable uncertainty in the resulting Ko values was
      found due to three main reasons. Firstly, obtaining 'free' Al data even with the
      DGT method is relatively difficult, leading to uncertainty in the data. Secondly,
      before Scatchard plots can be constructed, the maximum binding capacity (MBC)
      must be estimated. Any uncertainty in this MBC propagates into uncertainty
      associated with the final plots. Thirdly, as the final fitted Ko values are
      largely based on extrapolation, a small uncertainty in the fit of the binding
      data results in an appreciable uncertainty in the obtained Ko. Therefore, while
      trends in Ko for Al and DOM could easily be discerned and compared, the
      uncertainty in the Ko values hinders the application in quantitative speciation
      calculation. More comprehensive speciation models that avoid the use of Ko seem
      to fit better for this purpose.

PMID- 14975661
TI  - Bench-scale and field-scale evaluation of catechol 2,3-dioxygenase specific
      primers for monitoring BTX bioremediation.
AB  - The objective of this work was to test a molecular genetic method for in situ
      monitoring of aerobic benzene, toluene, and xylene (BTX) biodegrading
      microorganisms. Catechol 2,3-dioxygenase (C23DO) genes occur in bacteria that
      biodegrade benzene, toluene, xylenes, phenol, biphenyl, and naphthalene. A
      competitive quantitative polymerase chain reaction (QC-PCR) technique using a
      single set of primers specific for an entire subfamily of C23DO genes was
      recently developed. To determine whether bacteria containing these C23DO genes
      actually exist in environments contaminated by BTX, aerobic microcosms containing
      previously uncontaminated soil were amended with different aromatic hydrocarbons
      and DNA extracts were analyzed by QC-PCR for C23DO genes. Anaerobic microcosms
      were established to confirm that oxygen was also necessary for the enrichment of
      C23DO genes. Field testing was done at two sites undergoing monitored natural
      attenuation. In microcosm experiments naphthalene, m-xylene, and p-xylene
      strongly enriched for C23DO genes while benzene, toluene, and o-xylene produced
      only transient, weakly detectable genes. In the field study, C23DO genes were
      detected in groundwater samples contaminated with either xylenes or naphthalene.
      The results of this study demonstrated that molecular genetic techniques can
      provide an accurate and rapid method to detect microorganisms capable of aromatic
      hydrocarbon biodegradation. Such a technique would be useful for monitoring the
      effectiveness of aeration technologies and for documenting microbial processes
      for monitored natural attenuation.

PMID- 14975662
TI  - Improvement of cadmium ion removal by base treatment of juniper fiber.
AB  - Juniper is a small-diameter underutilized lignocellulosic material. We evaluated
      the efficacy of base-treated juniper fiber (BTJF) for cadmium (Cd2+) sorption and
      the viability of juniper fiber as a sorbent for removing Cd2+ from water. Fourier
      transform infrared spectroscopy analysis indicated that carboxylate ion is a
      major functional group responsible for Cd2+ sorption. The apparent ideal sodium
      hydroxide concentration for base treatment is approximately 0.5M. A batch
      sorption isotherm test showed that equilibrium sorption data were better
      represented by the Langmuir model than the Freundlich model. After base
      treatment, the maximum Cd2+ sorption loading, Qmax, was greatly improved (9.18
      29.54 mg/g), despite a decrease in specific surface area. A pseudo-second-order
      kinetic model fitted well for the sorption of Cd2+ onto BTJF. Initial metal ion
      concentration and treatment alkalinity were found to be major parameters
      influencing the kinetics of the sorption reaction. As a result of its strong
      ability to bind cadmium and its faster kinetics in low concentration, BTJF could
      be an inexpensive and efficient sorbent for removing heavy metals from stormwater
      runoff.

PMID- 14975663
TI  - Derivation of numerical values for the World Health Organization guidelines for
      recreational waters.
AB  - In April 2001, draft 'Guidelines' for safe recreational water environments were
      developed at a World Health Organization (WHO) expert consultation. Later the
      same month, these were presented and discussed at the 'Green Week' in Brussels
      alongside the on-going revision of the European Union Bathing Water Directive
      76/160/EEC. The WHO Guidelines cover general aspects of recreational water
      management as well as define water quality criteria for various hazards. For
      faecal pollution, these include faecal indicator organism concentrations and an
      assessment of vulnerability to faecal contamination. Central to the approach set
      out in the WHO Guidelines are: (i) the concept of beach profiling to produce a
      'sanitary inspection category' which implies a priori hazard assessment as a core
      management tool and (ii) the prediction of poor water quality to assist in real
      time risk assessment and public health protection. These management approaches
      reflect a harmonized approach towards the assessment and management of risk for
      water-related infectious disease being applied by WHO. Numerical microbiological
      criteria for intestinal enterococci are proposed in the new Guidelines. These
      were developed using a novel approach to disease burden assessment, which has
      been applied to both recreational waters and urban air quality. This paper
      explains the scientific rationale and mathematical basis of the new approach,
      which is not presented in the WHO Guidelines for recreational waters.

PMID- 14975664
TI  - Modelling particle size distribution dynamics in marine waters.
AB  - Numerical simulations were carried out to determine the particle size
      distribution (PSD) in marine waters by accounting for particle influx,
      coagulation, sedimentation and breakage. Instead of the conventional rectilinear
      model and Euclidean geometry, a curvilinear collision model and fractal scaling
      mathematics were used in the models. A steady-state PSD can be achieved after a
      period of simulation regardless of the initial conditions. The cumulative PSD in
      the steady state follows a power-law function, which has three linear regions
      after log-log transformation, with different slopes corresponding to the three
      collision mechanisms, Brownian motion, fluid shear and differential
      sedimentation. The PSD slope varies from -3.5 to -1.2 as a function of the size
      range and the fractal dimension of the particles concerned. The environmental
      conditions do not significantly alter the PSD slope, although they may change the
      position of the PSD and related particle concentrations. The simulation
      demonstrates a generality in the shape of the steady-state PSD in the ocean,
      which is in agreement with many field observations. Breakage does not affect the
      size distribution of small particles, while a strong shear may cause a notable
      change in the PSD for larger and fractal particles only. The simplified approach
      of previous works using dimensional analysis still offers valuable approximations
      for the PSD slopes, although the previous solutions do not always agree with the
      simulation results. The variation in the PSD slope observed in field
      investigations can be reproduced numerically. It is argued that non-steady-state
      conditions in natural waters could be the main reason for the deviation of PSD
      slopes. A change in the nature of the particles, such as stickiness, and
      environmental variables, such as particle input and shear intensity, could force
      the PSD to shift from one steady state to another. During such a transition, the
      PSD slope may vary to some extent with the particle population dynamics.

PMID- 14975665
TI  - Adsorptive removal of phosphate from aqueous solutions using iron oxide tailings.
AB  - This study explored the feasibility of utilizing industrial waste iron oxide
      tailings for phosphate removal in laboratory experiments. The experimental work
      emphasized on the evaluation of phosphate adsorption and desorption
      characteristics of the tailing material. The adsorption isotherm, kinetics, pH
      effect and desorption were examined in batch experiments. Five isotherm models
      were used for data fitting. The three-parameter equations (Redlich-Peterson and
      Langmuir-Freundlich) showed more applicability than the two-parameter equations
      (Freundlich, Langmuir and Temkin). A modified equation for calculation of the
      separation factor using the Langmuir-Freundlich equation constants was developed.
      The initial phosphate adsorption on the tailings was rapid. The adsorption
      kinetics can be best described by either the simple Elovich or power function
      equation. The phosphate adsorption on the tailings tended to decrease with an
      increase of pH. A phosphate desorbability of approximately 13-14% was observed,
      and this low desorbability likely resulted from a strong bonding between the
      adsorbed PO(4)(3-)and iron oxides in the tailings. Column flow-through tests
      using both synthetic phosphate solution and liquid hog manure confirmed the
      phosphate removal ability of the tailings. Due to their low cost and high
      capability, this type of iron oxide tailings has the potential to be utilized for
      cost-effective removal of phosphate from wastewater.

PMID- 14975666
TI  - Modeling of aerobic biodegradation of feces using sawdust as a matrix.
AB  - Composting in the bio-toilet system is a continuous thermophilic-aerobic
      biodegradation process. Unlike to the traditional composting systems,
      biodegradation rates of organic matter are very important because feces are daily
      added into the composting reactor of the bio-toilet and an accelerated
      decomposition is aimed. The models developed for conventional composting
      processes include simple formulations of biodegradation kinetics and deal mainly
      with energy and water balances. Therefore, formulation of kinetics that can
      reasonably describe the biodegradation process in the bio-toilet system is
      required for better modeling predictions. In this work, a bio-kinetic model was
      introduced to describe the aerobic biodegradation of feces in the bio-toilet
      system. This model includes three processes for carbonaceous material degradation
      and is prepared by using the activated sludge modeling techniques and
      formulations. Stoichiometric parameters were adopted from literature on activated
      sludge processes. Kinetic parameters were estimated by conducting batch tests for
      several organic loadings and by using respirometry, curve-fitting techniques, and
      sensitivity analysis. Feasibility and applicability of these parameters were
      assessed by conducting feces intermittent-feeding tests and by simulating the
      experimental respiration rates. Model, stoichiometric and kinetic parameters
      proved to be affordable for describing the biodegradation of feces in the bio
      toilet system.

PMID- 14975667
TI  - Optimization of PCR-based methods for rapid detection of Campylobacter jejuni,
      Campylobacter coli and Yersinia enterocolitica serovar 0:3 in wastewater samples.
AB  - PCR-based methods were evaluated for their adequacy to assess the removal of
      pathogens from wastewater samples. For the development and optimization of the
      methods, samples were taken at two different sites from two different constructed
      wetlands. Campylobacter jejuni/coli and Yersinia enterocolitica serogroup 0:3
      were selected as model pathogens and Enterococcus faecalis as a standard
      microbiological indicator. The chosen PCR protocols were optimized for wastewater
      DNA extracts in order to obtain high sensitivity and reproducibility
      independently of the background flora. All PCR protocols were successfully
      performed and reproducible with a background of up to 10(10) nontarget cells per
      reaction. Five cells of Y. enterocolitica, 50 cells of C. jejuni/coli, and 500
      cells of E. faecalis per 100ml treated water could be detected. The method
      detection limit in the settled wastewater was higher: 200 cells per 100ml for Y.
      enterocolitica, 2000 cells per 100ml for C. jejuni/coli, and 20,000 cells per
      100ml for E. faecalis. C. jejuni/coli and Y. enterocolitica PCRs were adapted to
      municipal wastewater, with higher loads of potential PCR inhibitors. Sensitivity
      was lower for this type of wastewater: 200 cells of Y. enterocolitica and 2000
      cells of C. jejuni/coli were detected per 100ml treated wastewater, 2500 cells of
      Y. enterocolitica and 25,000 cells of C. jejuni/coli per 100ml settled
      wastewater. The developed PCR methods enable the detection of C. jejuni/coli, Y.
      enterocolitica serogroup 0:3 and E. faecalis within 12h. They show specificity,
      reproducibility and low detection limits for the investigated pathogens.

PMID- 14975668
TI  - Separation of monovalent and divalent ions from aqueous solution by
      electrodialysis and nanofiltration.
AB  - The possibilities of separating monovalent and multivalent ions by
      electrodialysis (ED) and nanofiltration (NF) are explored. Five synthetic single
      salt solutions were applied to ED and NF: NaCl, Na(2)SO(4), MgCl(2), MgSO(4) and
      NaNO(3). Two combinations of anionic and cationic exchange membranes were
      evaluated for ED (AMV/CMV Selemion membranes and ACS/CMS Tokuyama membranes), and
      two membranes were evaluated for NF (NTR 7450 and UTC-60). The separation was
      evaluated using an alternative parameter, the separation efficiency, in order to
      compare ED and NF. The separation efficiency ranges from 0% (no separation) to
      100% (perfect separation). Both NF membranes had a good separation efficiency for
      the separation of monovalent and divalent anions (ca. 60%); the ED membranes
      performed worse. For the separation of monovalent and divalent cations, the UTC
      60 membrane was the best for the considered separation because of size exclusion
      effects for the larger divalent ion. The ACS/CMS membranes had a similar
      separation efficiency (ca. 60%); the NTR 7540 membrane and AMV/CMV ED membranes
      showed only a small separation.

PMID- 14975669
TI  - MGS0039: a potent and selective group II metabotropic glutamate receptor
      antagonist with antidepressant-like activity.
AB  - The present study describes the pharmacological profile of (1R,2R,3R,5R,6R)-2
      Amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic
      acid (MGS0039), a novel group II mGluR antagonist. MGS0039 showed high affinity
      for both mGluR2 (Ki = 2.2 nM) and mGluR3 (Ki = 4.5 nM), which are comparable to
      LY341495, another group II mGluR antagonist. MGS0039 attenuated both glutamate
      induced inhibition of forskolin-evoked cyclic AMP formation in CHO cells
      expressing mGluR2 (IC50 = 20 nM) or mGluR3 (IC50 = 24 nM) and glutamate-increased
      [35S]GTPgammaS binding to mGluR2 (pA2 = 8.2), which means that MGS0039 acts as an
      antagonist. MGS0039 shifted the dose-response curve of glutamate-increased
      [35S]GTPgammaS binding rightward without altering the maximal response, and
      thereby indicating competitive antagonism. MGS0039 showed no significant effects
      on other mGluRs as well as the other receptors and transporters we studied.
      MGS0039 (0.3-3 mg/kg, i.p.) as well as LY341495 (0.1-3 mg/kg, i.p.) had dose
      dependent antidepressant-like effects in the rat forced swim test and in the
      mouse tail suspension test. In contrast, MGS0039 (0.3-3 mg/kg, i.p.) had no
      apparent effect in the rat social interaction test and in the rat elevated plus
      maze. These results indicate that MGS0039 is a potent and selective antagonist of
      group II mGluR, and that group II mGluR antagonists, like MGS0039, have an
      antidepressant-like potential in experimental animal models.

PMID- 14975670
TI  - Blockade of glutamate mGlu5 receptors in a rat model of neuropathic pain prevents
      early over-expression of pro-apoptotic genes and morphological changes in dorsal
      horn lamina II.
AB  - We used rats with a sciatic nerve chronic constrictive injury (CCI) and combined
      behavioural, molecular and morphological approaches to assess the involvement of
      mGlu5 receptors in neuropathic pain-associated hyperalgesia and spinal cord
      neuron apoptosis. Mechanical and thermal hyperalgesia developed 2-3 days after
      surgery. Morphological changes in the ipsilateral L4-L5 lamina II consisted of:
      (i) cell loss (38 +/- 5%), (ii) increased TUNEL-positive profiles, (iii)
      decreased SP-immunoreactive primary afferents, and (iv) reactive gliosis.
      Molecular expression data suggested a bi-phasic response of bcl-2 family genes in
      CCI. An early (2-3 days post-CCI) E2F1- and p53-independent apoptosis appeared in
      the spinal cord as the pro-apoptotic bax gene increased (320 +/- 19%), followed
      by an increased expression of the anti-apoptotic bcl-2 and bcl-xL genes (60 +/-
      11% and 110 +/- 15%, respectively) 7 days from CCI. The selective mGlu5 receptor
      antagonist, MPEP (2 mg/kg i.p. twice daily), prevented the development of thermal
      hyperalgesia and transiently reduced mechanical hyperalgesia. Despite the MPEP
      treatment, which normalised bax/bcl-2 and bcl-xL/bcl-xS ratios at all times post
      CCI, mechanical hyperalgesia reappeared by 7 days after CCI. Similarly, MPEP was
      cytoprotective at 3, but not 7 days post-CCI. This study shows that: (a) spinal
      cord neuron loss may be triggered by a p53- and E2F1-independent apoptosis in
      lamina II with the participation of glutamate mGlu5 receptors, (b) these
      receptors seem to be involved transiently, as their blockade was no longer
      protective by 7 days CCI, and (c) this delayed cell death occurred in the absence
      of Bax activation, suggesting the involvement of an alternative death pathway.

PMID- 14975671
TI  - GABA(A), but not NMDA, receptors modulate in vivo NO-mediated cGMP synthesis in
      the rat cerebral cortex.
AB  - We have investigated the functional relationships between NMDA receptors and the
      NOS/sGC system in the rat pre-frontal cortex in vivo by microdialysis. cGMP basal
      levels were sensitive to NOS or sGC inhibitors (L-NARG or ODQ) or NO donors
      (SNAP) when enzymatic breakdown was blocked by the phosphodiesterase inhibitor
      IBMX, indicating that basal cGMP production derives, at least in part, from the
      NOS/sGC pathway activity and that the pre-frontal cortex possesses a very
      efficient degradation system for cGMP. The glutamate receptor agonist NMDA did
      not alter extracellular cGMP either in absence or presence of IBMX. cGMP was not
      augmented when NMDA was co-infused with the NOS substrate L-arginine, the glycine
      site agonist d-serine or the glutamate receptor agonist AMPA. Interestingly, the
      selective GABA(A) receptor antagonist bicuculline enhanced cGMP production,
      revealing that the cortical NOS/sGC system is tonically inhibited by endogenous
      GABA. However, in the presence of bicuculline, NMDA did not increase
      extracellular cGMP. In the presence of bicuculline, blockade of 5-HT1/2
      receptors, known to inhibit the NMDA/NOS/sGC pathway, with the antagonist
      methiothepin did not unmask cGMP elevations by NMDA. Thus, it would seem that
      NMDA receptors do not regulate cortical NOS/sGC activity that, on the other hand,
      is modulated by endogenous GABA acting at GABA(A) receptors.

PMID- 14975672
TI  - NAAG fails to antagonize synaptic and extrasynaptic NMDA receptors in cerebellar
      granule neurons.
AB  - The peptide transmitter N-acetylaspartylglutamate (NAAG) selectively activates
      the group II metabotropic glutamate receptors. Several reports also suggest that
      this peptide acts as a partial agonist at N-methyl-D-aspartate (NMDA) receptors
      but its putative antagonist effects have not been directly tested. To do this, we
      used whole cell recordings from cerebellar granule cells (CGC) in culture that
      allow the highest possible resolution of NMDA channel activation. When CGC were
      activated with equimolar concentrations of NMDA and NAAG, the peptide failed to
      alter the peak current elicited by NMDA. Very high concentrations of NAAG (100
      200 microM) did not significantly reduce the current elicited by 10 microM NMDA
      or 0.1 microM glutamate, while 400 microM NAAG produced only a very small (less
      than 15%) reduction in these whole cell currents. Similarly, NAAG (400 microM)
      failed to significantly alter the average decay time constant or the peak
      amplitude of NMDA receptor-mediated miniature excitatory post-synaptic currents
      (mEPSCs). We conclude that high concentrations of the peptide do not exert
      physiologically relevant antagonist actions on synaptic NMDA receptor activation
      following vesicular release of glutamate. As an agonist, purified NAAG was found
      to be at least 10,000-fold less potent than glutamate in increasing "background"
      current via NMDA receptors on CGC. Inasmuch as it is difficult to confirm that
      NAAG preparations are completely free from contamination with glutamate at the
      0.01% level, the peptide itself appears unlikely to have a direct agonist
      activity at the NMDA receptor subtypes found in CGC. Recent reports indicate that
      enhancing the activity of endogenous NAAG may be an important therapeutic
      approach to excitotoxicity and chronic pain perception. These effects are likely
      mediated by group II mGluRs, not NMDA receptors.

PMID- 14975673
TI  - Activation of dopamine D4 receptors modulates [3H]GABA release in slices of the
      rat thalamic reticular nucleus.
AB  - The thalamic reticular nucleus (nRt) is innervated by dopaminergic projections
      from the sustantia nigra compacta (SNc) and is rich in dopamine D4 receptors,
      however, the functional effects of dopamine on this structure are unknown. We
      examined whether the D1 receptor agonist SKF 38393, or the D2 class receptor
      agonist quinpirole, modify depolarization evoked Ca(2+)-dependent [3H]GABA
      release. SKF 38393 was without effects, whereas quinpirole inhibited [3H]GABA
      release with an IC50 of 81 +/- 33 nM. Dose-dependence determinations of agonists
      (quinpirole and PD 168, 077) and antagonists (L-745,870, U-101958, clozapine and
      raclopride) with different affinities for different D2 class subtype receptors
      showed that a D4 receptor mediates quinpirole inhibition. We used
      methylphenidate, an agent that acts by increasing interstitial dopamine, to
      determine whether endogenous dopamine modulates [3H]GABA release. Methylphenidate
      inhibited [3H]GABA release showing that the nRt contains sufficient endogenous
      dopamine to activate D4 receptors. This inhibition was completely reversed by
      selectively blocking D4 receptors with L-745,870 or U-101958 indicating that the
      catecholamine receptors that modulate GABA release are D4 receptors. Given the
      importance of the nRt in the control of attention, sensory processing and the
      generation of rhythmic activity during slow wave sleep, it is possible that
      abnormal nRt function may generate some of the manifestations of the disorders of
      dopaminergic transmission.

PMID- 14975674
TI  - 5-HT2 receptors differentially modulate dopamine-mediated auto-inhibition in A9
      and A10 midbrain areas of the rat.
AB  - 5-HT (20 microM) enhanced dopamine (DA) D2-like receptor mediated reduction of
      the firing rate of DA neurons in the substantia nigra pars compacta (A9) and
      ventral tegmental area (A10) in a rat midbrain slice preparation. Quinpirole (30
      nM) induced a mean reduction of the firing rate in A9 and A10 DA neurons to 64 +/
      4%, respectively, 71 +/- 5% of the baseline value. Bath application of 5-HT in
      the presence of quinpirole further reduced the firing rate to 37 +/- 7% in A9 and
      33 +/- 13% in A10. The 5-HT2 receptor agonist (+/-)-1-(2,5-dimethoxy-4
      iodophenyl)-2-aminopropane hydrochloride (DOI, 500 nM) enhanced quinpirole
      induced reduction of firing rate of A10 DA neurons, but not of A9 DA neurons,
      suggesting that different 5-HT receptor subtypes are involved in modulation of
      dopamine D2-like receptor mediated inhibition in the two regions. The selective 5
      HT2A receptor antagonist MDL100907 and the selective 5-HT2C receptor antagonist
      SB242084 (50 and 500 nM) both abolished the enhancement of quinpirole-induced
      reduction by either 5-HT or DOI, suggesting the involvement of direct and
      indirect (possibly via interneurons) modulation pathways in A10. The involvement
      of 5-HT and specific 5-HT2 receptors in augmentation of auto-inhibition in A10
      could have important implications for our understanding of the mechanism of
      atypical antipsychotic drug action.

PMID- 14975675
TI  - 5-HT has contrasting effects in the frontal cortex, but not the hypothalamus, on
      changes in noradrenaline efflux induced by the monoamine releasing-agent, d
      amphetamine, and the reuptake inhibitor, BTS 54 354.
AB  - There is extensive evidence for functional interactions between central
      noradrenergic and serotonergic neurones. Here, dual-probe microdialysis was used
      in freely-moving rats to compare the effects of 5-HT on noradrenergic
      transmission in the rat frontal cortex and hypothalamus. We studied the effects
      of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA; which depleted 5
      HT stores in both the frontal cortex and the hypothalamus), on spontaneous efflux
      of noradrenaline and on the noradrenergic responses to d-amphetamine, and the
      monoamine reuptake inhibitor, BTS 54 354. pCPA pretreatment alone did not affect
      spontaneous noradrenaline efflux in either brain region, whether or not alpha2
      autoreceptors were inactivated by administration of the alpha2-antagonist,
      atipamezole (1 mg/kg i.p). However, in the frontal cortex, pCPA pretreatment
      augmented the amplitude of, and prolonged, the noradrenergic response to local
      infusion of d-amphetamine (10 microM). In contrast, pCPA abolished the increase
      in cortical noradrenaline efflux induced by local infusion of BTS 54 354 (50
      microM). In the hypothalamus, pCPA did not affect the amplitude of the response
      to either of these agents but did prolong the effects of d-amphetamine on
      noradrenaline efflux. These findings suggest that serotonergic transmission has
      complex effects on the noradrenergic response to drugs that increase
      noradrenergic transmission in the frontal cortex, but has less influence in the
      hypothalamus.

PMID- 14975676
TI  - Neurofilament proteins and cAMP pathway in brains of mu-, delta- or kappa-opioid
      receptor gene knock-out mice: effects of chronic morphine administration.
AB  - Opiate addiction is associated with abnormalities of neurofilament (NF) proteins
      and upregulation of cAMP signaling in the brain, which may modulate neuronal
      plasticity. This study investigated, using gene-targeted mice lacking mu-, delta-
      or kappa-opioid receptors, the role of these receptors in modulating the basal
      activity and the chronic effects of morphine on both intracellular targets. In WT
      mice, chronic treatment (5 days) with morphine (20-100 mg/kg) resulted in
      decreases in the immunodensity of neurofilament (NF)-L in the cerebral cortex (14
      23%). In contrast, chronic morphine did not decrease NF-L in cortices of mu-,
      delta-, and kappa-KO mice, suggesting the involvement of the three types of
      opioid receptors in this effect of morphine. Also, the marked increase in
      phosphorylated NF-H induced by chronic morphine in WT mice (two-fold) was
      abolished in mu -KO mice. In cortex and/or striatum of mu-, delta- and kappa-KO
      mice, the basal immunodensities of Galphai1/2 proteins, the catalytic isoform
      (Calpha) of protein kinase A (PKA) and the total content of cAMP response element
      binding protein (CREB, the nuclear target of PKA) were not different from those
      of WT mice. In contrast, phosphorylated CREB (the active form of this
      transcription factor) was reduced in cortex and/or striatum (23-26%) of mu- and
      delta-KO mice, but not in kappa-KO animals. These results suggest that the
      endogenous opioid tone acting on mu-/delta-receptors tonically stimulate CREB
      activation in the brain. In cortex and/or striatum of WT mice, chronic morphine
      did not induce upregulation of the main components of the cAMP signaling pathway.
      In contrast, chronic morphine treatment in mu-KO mice, but not in delta- or kappa
      KO, resulted in a paradoxical upregulation of Galphai1/2 (12-19%), PKA (19-21%,)
      and phosphorylated CREB (21-73%), but not total CREB, in cortex and/or striatum.
      The induction of heterologous receptor adaptations in mu-KO mice may explain this
      paradoxical effect of morphine.

PMID- 14975677
TI  - Functional interaction among opioid receptor types: up-regulation of mu- and
      delta-opioid receptor functions after repeated stimulation of kappa-opioid
      receptors.
AB  - It has been widely accepted that repeated administration of kappa-opioid receptor
      agonists leads to the development of antinociceptive tolerance. The present study
      was designed to investigate the effect of repeated administration of a selective
      kappa-opioid receptor agonist (1S-trans)-3,4-dichloro-N-methyl-N-[2-(1
      pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride ((-)U-50,488H) on the mu-
      and delta-opioid receptor agonist-induced antinociception and G-protein
      activation in mice. The mice were injected either subcutaneously (s.c.) or
      intracerebroventricularly (i.c.v.) pretreated with saline or (-)U-50,488H once a
      day for seven consecutive days. Two hours after the last injection, the mice were
      challenged by either mu- or delta-opioid receptor agonist for the antinociceptive
      assay. Repeated treatment with (-)U-50,488H (s.c. or i.c.v.) significantly
      enhanced antinociceptive effect of both mu-opioid receptor agonist (morphine) and
      delta-opioid receptor agonists ([d-Ala2]deltorphin (DELT) and (+)-4-[(alphaR)
      alpha-((2S,5R)-4-allyl-2,5-dime thyl-1-piperazinyl)-3-methoxybenzyl]-N,N
      diethylbenzamide (SNC-80) compared to saline-treated groups. Under these
      conditions, repeated s.c. injection of (-)U-50,488H significantly enhanced both
      mu- and delta-opioid receptor agonist-stimulated [35S]GTPgammaS binding in the
      membrane of the thalamus. On the contrary, either repeated administration of
      morphine (s.c. or i.c.v.) or SNC-80 failed to affect the kappa-opioid receptor
      agonist-induced antinociception and G-protein activation. Taken together, these
      results suggest that repeated stimulation of kappa-opioid receptor markedly
      increases the functional mu- and delta-opioid receptors, whereas repeated
      stimulation of either mu- or delta-opioid receptor had no direct effect on kappa
      opioidergic function in mice.

PMID- 14975678
TI  - The sleep lipid oleamide may represent an endogenous anticonvulsant: an in vitro
      comparative study in the 4-aminopyridine rat brain-slice model.
AB  - cis-Oleamide (cOA) is a putative endocannabinoid, which modulates GABA(A)
      receptors, Na+ channels and gap-junctions (important targets for clinical and
      experimental anticonvulsants). Here we address the hypothesis that cOA possesses
      seizure limiting properties and might represent an endogenous anticonvulsant.
      Field potentials were recorded from the rat hippocampus and visual cortex. The
      effects of cOA, were compared to carbamazepine (CBZ), pentobarbital (PB) and
      carbenoxolone (CRX) on 4-Aminopyridine(4AP)-induced epileptiform discharges. CBZ
      (100 microM), PB (50 microM) and CRX (100 microM), but not cOA (64 microM),
      significantly attenuated the duration of the evoked epileptiform discharges in
      CA1. Interictal activity in CA3 was significantly depressed by CRX and cOA
      (irreversible by AM251), increased by CBZ and remained unaffected by PB. CBZ, PB
      and CRX abolished spontaneous ictal events and attenuated evoked ictal discharges
      in the visual cortex. cOA did not abolish spontaneous ictal events, but
      significantly (albeit weakly) reduced the duration of evoked ictal events. cOA
      and CRX, in contrast to CBZ or PB, caused a significant delay in the development
      of the evoked (tonic phase) epileptiform discharges. The weak effects of cOA seem
      independent of cannabinoid (CB1) receptors. Enzymatic cleavage and lack of
      specific antagonists for cOA confound simple interpretations of its actions in
      slices. Its high lipophilicity, imposing a permeability barrier, may also explain
      the lack of anticonvulsant activity. The effects of cOA may well be masked by
      release of the endogenous ligand upon ictal depolarisation as we demonstrate here
      for established endocannabinoids. cOA does not possess profound antiepileptic
      actions in our hands compared to CBZ, PB or CRX.

PMID- 14975679
TI  - Valproate reduced excitatory postsynaptic currents in hippocampal CA1 pyramidal
      neurons.
AB  - Valproate (VPA) is one of the most widely used antiepileptic drugs, and it is
      also increasingly used for the treatment of neuropsychological disorders and
      neuropathic pain, as well as migraine prophylaxis. However, the underlying
      cellular mechanisms of VPA on the synaptic physiology remain unclear. We
      investigated the effects of VPA on synaptic transmission using the in vitro rat
      hippocampal slice technique and whole-cell patch clamp recordings from CA1
      pyramidal neurons. Perfusion with VPA, at therapeutically attainable
      concentrations, decreased the amplitude of excitatory postsynaptic currents
      (EPSCs) evoked by Schaffer collateral stimulation, without modifying inhibitory
      postsynaptic currents (IPSCs). Furthermore, VPA induced a significant reduction
      of the non-NMDA EPSC (non-NMDA(EPSC)) component, without modifying the NMDA EPSC
      (NMDA(EPSC)) component. Paired pulse facilitation and EPSC variance were not
      significantly affected by VPA, indicating that VPA did not decrease transmitter
      release probability, which suggests a postsynaptic mechanism of action. We
      therefore conclude that VPA decreases excitatory synaptic activity through the
      modulation of postsynaptic non-NMDA receptors, without modifying synaptic
      inhibition, and that this reduction of excitation is, at least in part,
      responsible for the effects of VPA.

PMID- 14975680
TI  - Differences in toxicity of the catechol-O-methyl transferase inhibitors,
      tolcapone and entacapone to cultured human neuroblastoma cells.
AB  - Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors used
      as adjuncts to levodopa in the treatment of Parkinson's disease (PD). The use of
      tolcapone has been limited by its hepatotoxicity, the cause of which remains
      uncertain. Tolcapone compound is an uncoupler of mitochondrial respiration in
      isolated mitochondria and this action may be relevant to its effect on liver
      function. We have examined the actions of COMT inhibitors on cultured cells,
      comparing them with those of the classical uncoupler carbonyl cyanide p
      (trifluoromethoxy) phenylhydrazone (FCCP), in order to provide insight into their
      mechanism of potential toxicity. Tolcapone and FCCP were shown to be toxic to
      human neuroblastoma SH-SY5Y cells and caused a profound reduction in ATP
      synthesis. Entacapone was not toxic to SH-SY5Y. Tolcapone and FCCP were shown to
      be equally toxic to cells depleted of mtDNA and thus devoid of a functional
      respiratory chain. This study demonstrates that tolcapone markedly inhibits ATP
      synthesis in cultured cells mirroring the effects of a classical uncoupler.
      However its toxicity may also involve a mechanism independent of its effects upon
      oxidative phosphorylation.

PMID- 14975681
TI  - Chronic intermittent ethanol (CIE) administration in rats decreases levels of
      neurosteroids in hippocampus, accompanied by altered behavioral responses to
      neurosteroids and memory function.
AB  - The administration of ethanol on a chronic intermittent regimen (CIE) involving
      multiple withdrawal episodes is a model for ethanol dependence. After CIE, rats
      exhibited reduced seizure threshold, increased anxiety, tolerance to GABAergic
      sedative-hypnotic drugs, and changes in GABA(A) receptor function and subunit
      composition in hippocampus. Previous studies have shown that acute and chronic
      ethanol may induce changes in the levels of the neurosteroid 3alpha
      hydroxysteroid-5alpha-pregnan-20-one (3alpha, 5alpha-THP) in the brain.
      Therefore, the current study analyses the correlation between chronic
      intermittent ethanol effects on the level of 3alpha, 5alpha-THP in hippocampus of
      CIE rats and the behavioral changes in sensitivity to neurosteroids. After CIE,
      the levels for 3alpha, 5alpha-THP were significantly reduced in hippocampus of
      rats. The mRNA levels for the enzymes 5alpha-reductase and 3alpha-HSD in
      hippocampus were also reduced. In vivo, (in contrast to a tolerance to the
      hypnotic effect of steroids), CIE rats showed increased sensitivity to the
      anticonvulsant and to the anxiolytic effect of the steroid alphaxalone. Perhaps,
      this is a response to lowered levels of endogenous neuroactive steroids. CIE rats
      also showed impairment of hippocampus-dependent memory function. These results
      suggest that changes in neurosteroids level and in vivo sensitivity to these
      compounds are involved in the development of ethanol dependence in the CIE model.

PMID- 14975682
TI  - Enhanced binding activity of nuclear antioxidant-response element through
      possible formation of Nrf2/Fos-B complex after in vivo treatment with kainate in
      murine hippocampus.
AB  - To evaluate whether in vivo glutamate signals modulate signaling processes
      mediated by antioxidant-response element (ARE), we examined ARE binding in
      nuclear extracts from the hippocampus after in vivo treatment of mice with
      kainate. Enhancement of ARE binding was found at 2 h to 3 days after kainate
      treatment. Supershift analysis indicated possible involvement of Nrf2, Fos-B, and
      c-Fos in ARE binding in hippocampal nuclear extracts obtained from kainate
      treated animals. On super-supershift analysis by combination of these antibodies,
      ARE probe/protein complex was shifted by the anti-Fos-B antibody alone, but not
      by the anti-c-Fos antibody alone, and further addition of the anti-Nrf2 antibody
      dramatically eliminated binding of the complex shifted by the anti-Fos-B antibody
      in hippocampal nuclear extracts from kainate-treated animals. Kainate treatment
      induced a profound increase in levels of c-Fos and Fos-B, without markedly
      affecting that of Nrf2 in nuclear extracts from the hippocampus. Co-localization
      of Nrf2 with both Fos-B and c-Fos was found in neuronal cell layers of the
      hippocampus in kainate-treated animals. RT-PCR analysis revealed that kainate
      treatment increases glutathione-S-transferase mRNA level in the hippocampus.
      Taken together, kainate signals may enhance nuclear ARE binding through an
      interaction between constitutive Nrf2 with inducible Fos-B expressed in murine
      hippocampus.

PMID- 14975683
TI  - Evidence for the involvement of vanilloid receptor in the antinociception
      produced by the dialdeydes unsaturated sesquiterpenes polygodial and drimanial in
      rats.
AB  - This study investigated whether or not the neonatal treatment of rats with the
      sesquiterpenes polygodial or drimanial could cause persistent antinociception
      similar to that induced by capsaicin. Rats were injected subcutaneously 48 h
      after birth with capsaicin (50 mg/kg), polygodial (150 mg/kg), drimanial (150
      mg/kg) or vehicle (1ml/kg). Six to eight weeks later, rats were tested in models
      of nociception. Treatment of rats with capsaicin, polygodial or drimanial
      produced significant inhibition of the first phase and, to a lesser extent, the
      second phase of formalin-induced nociception. A significant reduction in Complete
      Freund's Adjuvant and capsaicin-induced hyperalgesia was observed in the animals
      neonatally treated with capsaicin, polygodial or drimanial compared with vehicle
      treated rats. Moreover, both sesquiterpenes caused inhibition of plasma
      extravasation induced by injection of capsaicin. The neonatal treatment with
      capsaicin, polygodial or drimanial significantly decreased [3H]-resiniferatoxin
      binding sites in the rat spinal cord, but only capsaicin neonatal treatment
      significantly reduced the expression of TRPV1 in dorsal root ganglia (DRG) when
      assessed by Western blot. These results extend our previous findings
      demonstrating that the neonatal treatment of rats with polygodial or drimanial,
      similar to that reported for capsaicin, produced persistent antinociception in
      adult animals associated with TRPV1 down-regulation in the spinal cord, but not
      TRPV1 expression in DRG.

PMID- 14975684
TI  - M-current modulators alter rat spinal nociceptive transmission: an
      electrophysiological study in vitro.
AB  - M-currents constitute a unique effector system to control neuronal excitability
      due to their voltage and ligand sensitivities. Here we have used retigabine, an M
      current agonist, and XE-991, an M-current antagonist, to study the possible
      involvement of these currents in the processing of spinal sensory and motor
      processing of nociceptive information in normal, untreated rats. Experiments were
      performed in a hemisected spinal cord preparation from rat pups using
      extracellular recordings. Responses to activation of nociceptive and non
      nociceptive afferent fibres were recorded. M-current modulators were bath applied
      to the entire cord or applied locally by pressure ejection. Retigabine and XE-991
      produced long-lasting and concentration-dependent effects on nociceptive reflexes
      showing only minor effects on non-nociceptive reflexes. Retigabine depressed
      responses to repetitive stimulation of the dorsal root recorded from motor
      neurones and dorsal horn neurones, whereas XE-991 showed the opposite
      potentiatory effect and reversed effects of retigabine. Local application of the
      modulators close by motor nuclei produced changes in reflex responses similar to
      those caused by bath application. These results constitute a clear indication of
      the existence of functional M-currents in dorsal and ventral horn elements of the
      mammalian spinal cord where they may serve to regulate early sensory and motor
      processing of nociceptive information. The weak effect of modulators on non
      nociceptive reflexes suggest that M-currents constitute a promising novel target
      for analgesics.

PMID- 14975685
TI  - Orchestration of synaptic plasticity through AKAP signaling complexes.
AB  - Significant progress has been made toward understanding the mechanisms by which
      organisms learn from experiences and how those experiences are translated into
      memories. Advances in molecular, electrophysiological and genetic technologies
      have permitted great strides in identifying biochemical and structural changes
      that occur at synapses during processes that are thought to underlie learning and
      memory. Cellular events that generate the second messenger cyclic AMP (cAMP) and
      activate protein kinase A (PKA) have been linked to synaptic plasticity and long
      term memory. In this review we will focus on the role of PKA in synaptic
      plasticity and discuss how the compartmentalization of PKA through its
      association with A-Kinase Anchoring Proteins (AKAPs) affect PKA function in this
      process.

PMID- 14975686
TI  - An NMDAR-independent LTP mediated by group II metabotropic glutamate receptors
      and p42/44 MAP kinase in the dentate gyrus in vitro.
AB  - The induction of long-term potentiation (LTP) under conditions of blockade of the
      N-methyl-D-aspartate receptor (NMDAR) was studied in the medial perforant path to
      granule cell synapse in the dentate gyrus. A small amplitude NMDAR-independent
      potentiation was induced by a single brief high frequency stimulation (HFS), and
      a summated larger LTP was induced by repeated spaced HFS. The NMDAR-independent
      LTP was mediated by activation of group II mGluR as it was inhibited by the group
      II antagonists EGLU and also low concentrations of LY341495, but not the group I
      mGluR antagonist MPEP. Perfusion of the group II mGluR agonist DCG-IV induced
      NMDAR-independent LTP in media containing an NMDAR antagonist. The NMDAR
      independent LTP induced by HFS was mediated via activation of p42/44 MAP kinase
      as it was blocked by the selective inhibitor PD98059.

PMID- 14975687
TI  - Hypoxia alters GABAA receptor function and subunit expression in NT2-N neurons.
AB  - Hypoxia causes dysfunction of excitatory and inhibitory neurotransmission, often
      resulting in encephalopathy, seizures or myoclonus. We evaluated the effects of
      hypoxia on GABAA receptor (GABAAR) function and expression in an in vitro model
      of neuronal hypoxia. NT2-N cells, derived from the human NT2 teratocarcinoma cell
      line, were exposed to < or =1% O2 for 8 h and then used immediately for
      experiments or allowed to recover under normoxic conditions (95% air/5% CO2) for
      24, 48 or 96 h. Hypoxic treatment did not cause obvious morphological changes or
      cell death. In whole-cell patch-clamp recordings, the GABA current EC50 was
      unchanged, however, maximal GABA-evoked currents changed in a biphasic manner.
      Maximal GABA currents were significantly increased immediately after hypoxia, but
      were significantly reduced after 48 h normoxic recovery, and then returned to
      baseline after 96 h recovery. Maximal potentiation of 10 microM GABA currents by
      diazepam was increased 48 h after hypoxia, but potentiation by zolpidem was
      decreased. Barbiturate enhancement and zinc inhibition of GABA currents were
      unchanged. Semiquantitative reverse transcriptase (RT)-PCR showed decreased
      alpha1, alpha5, beta2 and gamma2 subunit mRNA after hypoxia. Hypoxic exposure
      altered GABAAR physiology and subunit mRNA expression, which may correlate with
      symptoms observed after hypoxia in vivo.

PMID- 14975688
TI  - Glutamate receptor activation is involved in 5-HT2 agonist-induced Arc gene
      expression in the rat cortex.
AB  - Brain 5-HT regulates the expression of gene transcription factor as well as novel
      effector immediate early genes (IEGs). The 5-HT regulation of the gene
      transcription factor IEG, c-fos, involves activation of 5-HT2A and ionotropic
      glutamate receptors. Here, we investigate whether these receptors are also
      involved in the regulation of the effector IEG, Arc. In rats, the 5-HT2 agonist
      DOI induced a marked increase in expression of Arc mRNA in a variety of cortical
      regions. This effect was blocked by the selective 5-HT2A receptor antagonist, MDL
      100,907, but not the 5-HT(2B/2C) receptor antagonist, SB206553. The AMPA receptor
      antagonist GYKI 52466 also attenuated DOI-induced Arc mRNA expression, as did the
      NMDA receptor antagonist MK801 in some regions. Immunofluorescence studies showed
      that DOI increased Arc-immunoreactivity in cortical cells that expressed AMPA and
      NMDA receptor subunits but not the 5-HT2A receptor. Finally, DOI-induced Arc
      immunoreactivity in cortical cells was extensively co-localised with c-fos
      immunoreactivity. These results suggest that, as with c-fos expression,
      ionotropic glutamate receptors (AMPA and NMDA) are involved in 5-HT2A receptor
      induced Arc expression. This finding, together with evidence of extensive Arc and
      c-fos co-localisation, suggests that 5-HT2A receptor activation may induce the
      expression of both effector and transcription factor IEGs via common molecular
      and cellular substrates.

PMID- 14975689
TI  - Fluvoxamine, a selective serotonin reuptake inhibitor, suppresses
      tetrahydrobiopterin in the mouse hippocampus.
AB  - In the present study, we investigated the effects of fluvoxamine, a selective
      serotonin reuptake inhibitor, on brain tetrahydrobiopterin (BH4) levels. We
      directly measured levels of BH4 by Tani and Ohno's direct method as well as the
      serotonin (5-HT) turnover ratio, i.e. 5-hydroxyindoleacetic acid (5-HIAA)/5-HT,
      after sub-acute s.c. injection of fluvoxamine in the hippocampus of mice. Our
      animal model incorporated two risk factors of depression, social isolation and
      acute environmental change. Male ddY mice (6W) were housed in isolation (1 per
      cage; 35 days), injected with fluvoxamine (20 or 40 mg/kg; days 29-35), and
      exposed to novelty stress (20 min; day 35). In the stress session, behavioral
      parameters, i.e. total distance and rearing behavior, were measured. Isolation
      housing increased both behaviors. Fluvoxamine attenuated rearing behavior, but
      did not influence total distance. Isolation housing increased BH4 levels. Novelty
      stress increased BH4 levels in group housing, although it did not change them in
      isolation housing. Fluvoxamine suppressed BH4 levels. In isolation housing,
      fluvoxamine increased 5-HT turnover ratios, while it decreased them in group
      housing. In conclusion, fluvoxamine, housing condition, and novelty stress
      regulated BH4 levels. Fluvoxamine may have changed behavior and 5-HT turnover by
      suppressing BH4 levels as well as by inhibiting 5-HT reuptake.

PMID- 14975690
TI  - Chronic nicotine differentially alters cocaine-induced locomotor activity in
      adolescent vs. adult male and female rats.
AB  - Tobacco use is prevalent in the adolescent population. It is a major concern
      because tobacco is highly addictive and has also been linked to illicit drug use.
      There is not much research, however, on the interaction between nicotine and
      other stimulant drugs in animal models of early adolescence. This study examined
      the effects of chronic nicotine alone and on cocaine-stimulated activity in male
      and female periadolescent rats compared to male and female adult rats. During the
      seven-day nicotine pretreatment period, nicotine increased locomotor activity in
      all groups compared to vehicle controls. Male and female adult rats and female
      periadolescent rats developed sensitization to the locomotor-activating effects
      of nicotine over the 7-day treatment period, while male periadolescent rats did
      not. All groups treated with nicotine, however, exhibited sensitization to
      nicotine-induced repetitive motion over the 7-day nicotine treatment period. On
      day 8, male periadolescent rats pretreated with nicotine were more markedly
      sensitized to the locomotor-activating effects of cocaine than male adult rats,
      while female rats pretreated with nicotine were not sensitized to cocaine. In
      contrast, male and female periadolescent rats, but not adult rats, had increased
      amounts of repetitive beam breaks induced by cocaine after nicotine pretreatment.
      Overall, it appears that cross-sensitization to cocaine is greater in
      periadolescent than in adult rats, and that males are more sensitized than
      females. Thus, it may be that nicotine use during adolescence carries a greater
      risk than during adulthood and that male adolescents may be particularly
      vulnerable to the risk of cocaine abuse after nicotine use. This information
      should be taken into account so as to help us better understand the development
      of drug addiction in adolescents compared to adults.

PMID- 14975691
TI  - The role of nicotinic receptor alpha 7 subunits in nicotine discrimination.
AB  - The subtypes of nicotinic receptors at which the behavioural effects of nicotine
      originate are not fully understood. The experiments described here use mice
      lacking the alpha7 subunit of nicotinic receptors to investigate the role of
      alpha7-containing receptors in nicotine discrimination. Wild-type and alpha7
      knockout mice were trained in a two-lever nicotine discrimination procedure using
      a tandem schedule of food reinforcement. Mutant mice exhibited baseline rates of
      lever-pressing as low as 52.2% of rates in wild-type controls (n=21-24). Mutant
      and wild-type mice acquired discrimination of nicotine (0.4 or 0.8 mg/kg) at a
      similar rate (n=10-12) and reached similar final levels of accuracy (71.9 +/-
      4.4% and 90.8 +/- 3.1% after 60 training sessions for 0.4 and 0.8 mg/kg training
      doses, respectively, in mutant mice, as compared with 75.0 +/- 6.5% and 87.6 +/-
      4.8% for wild types). The genotypes exhibited similar steep dose-response curves
      for nicotine discrimination. In both genotypes, dose-response curves for mice
      trained with 0.8 mg/kg of nicotine were displaced three- to four-fold to the
      right as compared with those for the mice trained with the smaller dose. The
      predominant effect of nicotine on the overall rate of responding was a reduction
      at the largest doses tested and there was no difference between the genotypes.
      The results suggest that nicotinic receptors containing the alpha7 subunit do not
      contribute to the discriminative stimulus or response-rate-depressant effects of
      nicotine, although they may regulate baseline rates of operant responding.

PMID- 14975692
TI  - Voltage gated P/Q and N-type calcium channels mediate the nicotinic facilitation
      of GABAergic and glycinergic inputs to cardiac vagal neurons.
AB  - Previous work has shown endogenous cholinergic activity facilitates both
      GABAergic and glycinergic neurotransmission to premotor cardiac vagal neurons.
      Exogenous application of nicotine increases the frequency of glycinergic and
      GABAergic inhibitory postsynaptic currents (IPSCs) and miniature IPSCs (mIPSCs)
      to cardiac vagal neurons. In this study we examined whether the nicotine evoked
      facilitation of GABAergic and glycinergic neurotransmission to cardiac vagal
      neurons is dependent or independent of activation of voltage dependent calcium
      channels. Nicotine evoked increases in GABAergic and glycinergic mIPSCs in
      cardiac vagal neurons which were blocked by the non-specific calcium channel
      antagonist cadmium (100 microM). Application of the L (Cav 1) type calcium
      channel antagonist nimodipine (10 microM) had no effect. However, the increase in
      both GABAergic and glycinergic mIPSCs elicited by nicotine was abolished by the
      P/Q (Cav 2.1) voltage gated calcium channel antagonist omega-agatoxin IVA (100
      nM). Omega-conotoxin GVIA (1 microM), a specific blocker of N (Cav 2.2) type
      voltage gated calcium currents, inhibited the nicotine elicited augmentation of
      GABA and abolished the increase in glycine mIPSC frequency. This work
      demonstrates that the nicotine evoked facilitation of GABAergic and glycinergic
      neurotransmission to cardiac vagal neurons is dependent upon activation of P/Q
      (Cav 2.1) and N (Cav 2.2) type calcium channels.

PMID- 14975693
TI  - Detection of cannabinoid agonist evoked increase in BOLD contrast in rats using
      functional magnetic resonance imaging.
AB  - BOLD-contrast functional magnetic resonance imaging (fMRI) was used to
      investigate the effects of the synthetic cannabinoid agonist HU210 on the rat
      brain in order to determine potential CNS sites of action for the functional
      effects of cannabinoids. After obtaining basal data, rats (n=8) were given the
      cannabinoid agonist HU210 (10 microg/kg i.v.) and volume data sets collected for
      85 mins. Significant increases in functional BOLD activity were observed in
      specific brain regions including those important in pain (PAG), reward (VTA and
      accumbens) and motor function (striatum). In order to confirm cannabinoid
      receptor involvement in the HU210 evoked functional BOLD activity, rats (n=8)
      were pre-treated with the CB1 cannabinoid receptor antagonist SR141716A (100
      microg/kg i.v.) prior to HU210. Pretreatment with SR141716A abolished all
      significant evoked HU210 functional BOLD activity. To exclude the involvement of
      potential systemic effects induced by the cannabinoid agonist administration on
      the observed evoked functional BOLD activity a separate experiment investigated
      the effect of HU210 (10 microg/kg i.v.) on mean arterial pressure and showed that
      HU210 had no significant effect on pressure under chloral hydrate anaesthesia. In
      summary, this study demonstrates that the cannabinoid agonist HU210 evokes a
      significant increase in BOLD functional activity in specific regions and that
      this was cannabinoid receptor mediated. Furthermore the study indicates the
      potential value of fMRI in rodents to delineate pharmacologically induced changes
      in regional brain function.

PMID- 14975694
TI  - Somatostatin inhibits glutamate release from mouse cerebrocortical nerve endings
      through presynaptic sst2 receptors linked to the adenylyl cyclase-protein kinase
      A pathway.
AB  - The effects of somatostatin (SRIF, somatotropin release inhibiting factor) on the
      release of glutamate have been investigated using superfused mouse
      cerebrocortical synaptosomes. SRIF-14 inhibited the K+ (12 mM)-evoked overflow of
      preaccumulated [3H]D-aspartate as well as that of endogenous glutamate. Cyanamid
      154806, a selective sst2 receptor antagonist, but not BIM-23056, an antagonist at
      sst5 receptors, prevented the SRIF-14 effect. Octreotide and L779976, selective
      agonists at sst2 receptors, mimicked SRIF-14, whereas L797591, L796778, L803087
      and L362855, selective agonists at sst1, sst3, sst4 and sst5 receptor subtypes,
      were inactive. Activation of sst2 receptors seems to involve inhibition of the
      adenylyl cyclase-protein kinase A pathway present in glutamatergic terminals
      since the adenylyl cyclase inhibitor MDL-12,330A and the protein kinase A
      inhibitor H89 prevented the K+-evoked [3H]D-aspartate overflow. Consistent with
      the involvement of adenylyl cyclase, depolarization with 12 mM K+ increased
      synaptosomal cyclic AMP (cAMP) content, while forskolin, an adenylyl cyclase
      activator, potentiated basal [3H]D-aspartate release in an octreotide-, MDL
      12,330A- and H89-sensitive manner. To conclude, glutamatergic cerebrocortical
      nerve endings possess release-inhibiting sst2 receptors which represent potential
      targets for new drugs able to mitigate the effects of excessive glutamate
      transmission.

PMID- 14975695
TI  - Imidazenil: a potent and safe protective agent against diisopropyl
      fluorophosphate toxicity.
AB  - Convulsions are major and life-threatening signs of organophosphate (OP) nerve
      agents induced neurotoxicity. Thus, early intervention with anticonvulsant drugs
      to control seizure propagation and the consequent irreversible neuronal damage
      that may occur during OP exposure is essential. Diazepam is the standard
      anticonvulsant used in the therapeutic management of OP poisoning. However, its
      use has been associated with several unwanted effects including, sedation,
      amnesia, and in the large doses used for such treatment, respiratory depression.
      Moreover, protracted administration of diazepam has been associated with
      tolerance and dependence liabilities. In this study, we compared the efficacy and
      safety of diazepam (full allosteric modulator of GABA action) to that of
      imidazenil (partial, selective allosteric modulator of GABA action) as preventive
      treatment against diisopropyl fluorophosphate (DFP)-induced convulsions and
      mortality. Our results show that imidazenil is more potent and efficacious than
      diazepam in protecting rats against DFP-induced convulsions and death. Moreover,
      imidazenil was effective at doses (1 and 0.5 mg/kg) we have previously shown to
      be devoid of sedation, amnesia, respiratory depression, or tolerance and/or
      dependence. In contrast, diazepam was effective at doses (5 and 2.5 mg/kg) that
      produce sedation, amnesia, and ataxia. Furthermore, the combination of imidazenil
      with atropine was more potent and efficacious than that with diazepam.

PMID- 14975696
TI  - Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell
      death induced by activated microglia.
AB  - The phosphodiesterase inhibitor, ibudilast, has many effects on lymphocytes,
      endothelial cells, and glial cells. We examined the neuroprotective role of
      ibudilast in neuron and microglia co-cultures. Ibudilast significantly suppressed
      neuronal cell death induced by the activation of microglia with
      lipopolysaccharide (LPS) and interferon (IFN)-gamma. To examine the mechanisms by
      which ibudilast exerts a neuroprotective role against the activation of
      microglia, we examined the production of inflammatory and anti-inflammatory
      mediators and trophic factors following ibudilast treatment. In a dose-dependent
      manner, ibudilast suppressed the production of nitric oxide (NO), reactive oxygen
      species, interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha and
      enhanced the production of the inhibitory cytokine, IL-10, and additional
      neurotrophic factors, including nerve growth factor (NGF), glia-derived
      neurotrophic factor (GDNF), and neurotrophin (NT)-4 in activated microglia. Thus,
      ibudilast-mediated neuroprotection was primarily due to the inhibition of
      inflammatory mediators and the upregulation of neurotrophic factor. In the CA1
      region of hippocampal slices, long-term potentiation (LTP) induced by high
      frequency stimulation (HFS) could be inhibited with LPS and interferon-gamma
      stimulation. Ibudilast returned this LTP inhibition to the levels observed in
      controls. These results suggest that ibudilast may be a useful neuroprotective
      and anti-dementia agent counteracting neurotoxicity in activated microglia.

PMID- 14975697
TI  - Prolactin-releasing peptide affects pain, allodynia and autonomic reflexes
      through medullary mechanisms.
AB  - Prolactin-releasing peptide (PrRP) and neuropeptide FF (NPFF) are RF-amide
      peptides expressed in brain areas involved in pain modulation. NPFF displays
      multiple effects on acute, inflammatory and neuropathic pain. The potential role
      of PrRP in pain was addressed by intrathecal and intracerebral injections of PrRP
      on pain-related responses in both neuropathic and normal rats. Particularly in
      the dorsal medulla, PrRP produced significant antinociception in normal rats and
      an antiallodynic effect in neuropathic rats. To understand the basis of PrRP
      induced pain modulation, distributions of PrRP, PrRP receptor, and NPFF were
      compared in the rat central nervous system. PrRP and NPFF mRNA were expressed in
      different parts of the nucleus of the solitary tract. In the medulla, PrRP
      receptor mRNA expression was abundant only in area postrema. Of the peptides
      studied, only NPFF mRNA was found in the dorsal horn of the spinal cord and
      spinal nucleus of the trigeminal nerve. PrRP-immunoreactivity corresponded to the
      mRNA distribution. Even if the neuronal groups producing NPFF and PrRP were
      distinct, the fiber networks immunoreactive for PrRP and NPFF overlapped. The
      results show that PrRP modulates nociception due to supraspinal rather than
      spinal action, and that its antinociceptive mechanism differs from that
      previously characterized for NPFF.

PMID- 14975698
TI  - Heterologous expression and functional analysis of rat Nav1.8 (SNS) voltage-gated
      sodium channels in the dorsal root ganglion neuroblastoma cell line ND7-23.
AB  - The voltage-gated sodium channel NaV1.8 (SNS, PN3) is thought to be a molecular
      correlate of the dorsal root ganglion (DRG) tetrodotoxin resistant (TTX-R) Na+
      current. TTX-R/NaV1.8 is an attractive therapeutic drug target for inflammatory
      and neuropathic pain on the basis of its specific distribution in sensory
      neurones and its modulation by inflammatory mediators. However, detailed analysis
      of recombinant NaV1.8 has been hampered by difficulties in stably expressing the
      functional protein in mammalian cells. Here, we show stable expression and
      functional analysis of rat NaV1.8 (rNaV1.8) in the rat DRG/mouse N18Tg2
      neuroblastoma hybridoma cell line ND7-23. Rat NaV1.8 Na+ currents were recorded
      (789 +/- 89 pA, n=62, over 20-cell passages) that qualitatively resembled DRG TTX
      R in terms of gating kinetics and voltage-dependence of activation and
      inactivation. The local anaesthetic drug tetracaine produced tonic inhibition of
      rNaV1.8 (mean IC50 value 12.5 microM) and in repeated gating paradigms (2-10 Hz)
      also showed frequency-dependent block. There was a correlation between the
      ability of several analogues of the anticonvulsant/analgesic compound lamotrigine
      to inhibit TTX-R and rNaV1.8 (r=0.72, P<0.001). RT-PCR analysis of wild type ND7
      23 cells revealed endogenous expression of the beta1 and beta3 accessory Na+
      channel subunits-the possibility that the presence of these subunits assists and
      stabilises expression of rNaV1.8 is discussed. We conclude that the neuroblastoma
      ND7-23 cell line is a suitable heterologous expression system for rNaV1.8 Na+
      channels in that it allows stable expression of a channel with biophysical
      properties that closely resemble the native TTX-R currents in DRG neurones. This
      reagent will prove useful in the search for pharmacological inhibitors of rNaV1.8
      as novel analgesics.

PMID- 14975699
TI  - Evidence for a protective role played by the Na+/Ca2+ exchanger in cerebral
      ischemia induced by middle cerebral artery occlusion in male rats.
AB  - In the present paper, the role played by Na+/Ca2+ exchanger (NCX) in focal
      cerebral ischemia was investigated. To this aim, permanent middle cerebral artery
      occlusion (pMCAO) was performed in male rats. The effects on the infarct volume
      of some inhibitors, such as tyrosine-6 glycosylated form of the exchanger
      inhibitory peptide (GLU-XIP), benzamil derivative (CB-DMB) and
      diarylaminopropylamine derivative (bepridil), and of the NCX activator, FeCl3,
      were examined. FeCl3, CB-DMB, bepridil and GLU-XIP, a modified peptide
      synthesized in our laboratory in order to facilitate its entrance into the cells
      through the glucose transporter, were intracerebroventricularly (i.c.v.) infused.
      FeCl3 (10 microg/kg) was able to reduce the extension of brain infarct volume.
      This effect was counteracted by the concomitant icv administration of CB-DMB (120
      microg/kg). All NCX inhibitors, GLU-XIP, CB-DMB and bepridil, caused a worsening
      of the brain infarct lesion. These results suggest that a stimulation of NCX
      activity may help neurons and glial cells that are not irreversibly damaged in
      the penumbral zone to survive, whereas its pharmacological blockade can
      compromise their survival.

PMID- 14975700
TI  - Interplay between PACAP and NO in mouse ileum.
AB  - We investigated the possibility that pituitary adenylate cyclase activating
      peptide (PACAP) has a role in the control of contractility in the mouse ileum.
      PACAP-(1-27) produced tetrodotoxin (TTX)-insensitive, concentration-dependent
      reduction of the amplitude of the spontaneous contractions of longitudinal muscle
      up to their complete disappearance. This effect was inhibited by PACAP-(6-38),
      PACAP receptor antagonist, and by apamin, blocker of small-conductance Ca2+
      activated K+-channels. Nomega-nitro-L-arginine methyl ester (L-NAME), nitric
      oxide (NO) synthase inhibitor, reduced the PACAP-inhibitory response, and the
      joint application of apamin plus L-NAME produced additive effects. 1H-[1,2,4]
      oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), inhibitor of NO-stimulated soluble
      guanylate cyclase, significantly reduced the effect of PACAP. Exogenous NO, given
      as sodium nitroprusside (SNP), induced a concentration-dependent suppression of
      the phasic contractions, which was unaffected by apamin but reduced by either
      PACAP-(6-38) or TTX. Neurally evoked muscular relaxation was deeply antagonised
      by L-NAME. PACAP-(6-38) induced a reduction of the response to EFS only in the
      absence L-NAME. In conclusion, our results suggest that PACAP controls smooth
      muscle contractility, acting directly on the muscle cells through PACAP-27
      preferring receptors coupled to apamin-sensitive Ca2+-dependent K+-channels and
      indirectly through the stimulation of NO production. In turn, NO would stimulate
      the release of PACAP from inhibitory neurones.

PMID- 14975701
TI  - Involvement of Na+/H+ exchanger in hypoxia/re-oxygenation-induced neonatal rat
      cardiomyocyte apoptosis.
AB  - Although increased Na(+)/H(+) exchanger type-1 (NHE-1) activity has been
      implicated in the pathogenesis of myocardial infarction, the role of NHE-1 in
      induction of apoptosis, and the potential mechanisms involved have not been fully
      characterized. This study tested the hypothesis that NHE-1 activity is involved
      in hypoxia (H)/re-oxygenation (Re)-induced cardiomyocyte apoptosis by increasing
      mitochondrial Ca(2+) ([Ca(2+)]m). Primary cultured neonatal rat cardiomyocytes
      were subjected to 4.5 h of H followed by 12 h of Re. Relative to H alone, the
      level of X-rhod-1 acetoxymethyl (AM)-labeled [Ca(2+)]m was increased, and the
      frequency of cell death (propidium iodide (PI) staining) and apoptotic cells
      (terminal deoxynucleotidyl transferase (TdT)-mediated-UTP nick end labeling
      [TUNEL]), confirmed by Annexin-V, were augmented at the end of Re, along with
      appearance of cytosolic cytochrome c, activation of caspase-3, and increased
      ratio of Bax and Bcl-2. Addition of cariporide (20 micromol/l), a well-known NHE
      1 inhibitor, to cultured cells before H significantly reduced [Ca(2+)]m, the
      number of PI and TUNEL positive cells relative to the levels at end of Re, but
      did not completely eliminate these changes compared to Sham control. There was a
      strong trend for attenuation in increased levels of [Ca(2+)]m, and the number of
      PI and TUNEL positive cells when same dose of cariporide was added only at Re,
      but the difference in these variables did not reach significance. In contrast,
      the levels of [Ca(2+)]m and the number of PI and TUNEL positive cells were
      significantly reduced to a level comparable to Sham control when cariporide (20
      micromol/l) was administered before H and during Re, respectively, associated
      with a reduction in cytosolic cytochrome c, caspase-3 activity and ratio of Bax
      and Bcl-2. In conclusion, these data suggest that NHE-1 is involved in induction
      of cardiomyocyte apoptosis during both H and Re through a [Ca(2+)]m-dependent
      manner, thereby resulting in activation of cytochrome c-caspase-3 signaling
      pathways.

PMID- 14975702
TI  - Y-26763: ATP-sensitive K+ channel activation and the inhibition of insulin
      release from human pancreatic beta-cells.
AB  - The effect of Y-26763 [(-)-(3S,4R)-4-(N-acetyl-N-hydroxyamino)-6-cyano-3,4
      dihydro-2,2-dimethyl-2H-1-benzopyran-3-ol], a novel ATP-sensitive K(+) (K(ATP))
      channel activator, was tested on insulin secretion from human pancreatic islets
      in vitro. Y-26763 was able to inhibit both glucose- and tolbutamide-induced
      insulin secretion from islets as assessed by radioimmunoassay. The mechanism for
      inhibition of insulin secretion was characterised using patch clamp
      electrophysiology on dispersed human pancreatic beta-cells which express K(ATP)
      channels comprised of Kir6.2 and SUR1, and the NES2Y human beta-cell line,
      transfected with Kir6.2DeltaC26. Y-26763 activated K(ATP) channels in a
      reversible manner with a similar activity to diazoxide. This required the
      presence of hydrolysable nucleotides and appeared to be mediated by interaction
      of Y-26763 with SUR1 since: (a) tolbutamide was able to reverse the actions of Y
      26763 and (b) Y-26763 failed to activate Kir6.2DeltaC26 in the absence of SUR1.
      We conclude that Y-26763-induced inhibition of insulin release is dependent upon
      the activation of K(ATP) channels in human beta-cells.

PMID- 14975703
TI  - Expression of adhesion molecules by sphingosine 1-phosphate and histamine in
      endothelial cells.
AB  - We investigated the effects of sphingosine 1-phosphate and histamine on the
      expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion
      molecule-1 (ICAM-1) and E-selectin, and their signaling pathways in human
      umbilical vein endothelial cells. Sphingosine 1-phosphate increased the mRNA and
      protein level of VCAM-1, and the mRNAs of E-selectin and ICAM-1. The effects of
      sphingosine 1-phosphate were inhibited by the pertussis toxin and the respective
      inhibitors (10 microM 1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17
      yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122) for phosphoinositide-specific
      phospholipase C; 10 microM 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4
      pyridyl)-1H-imidazole (SB203580) for p38 mitogen-activated protein kinase (MAPK);
      1 microM 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3
      a)pyrrolo(3,4-c)-carbazole (Go6976) for the alpha form of protein kinase C (PKC
      alpha)), but not by a PKC-delta inhibitor (1 microM rottlerin). Histamine, which
      alone showed no effect, enhanced the sphingosine 1-phosphate-induced expressions
      via histamine H(1) receptor. The histamine response decreased by U73122 and
      rottlerin, but not by SB203580 and Go6976. The effects of sphingosine 1-phosphate
      with and without histamine were abolished by the higher concentrations of PKC
      inhibitors and in the PKC-depleted cells. Sphingosine 1-phosphate and histamine
      alone stimulated phosphorylation of p38 MAPK in a phosphoinositide-specific
      phospholipase C-dependent but not in a PKCs-independent manner. These findings
      suggest that sphingosine 1-phosphate-induced expression of adhesion molecules was
      mediated by phosphoinositide-specific phospholipase C and preferentially by PKC
      alpha and p38 MAPK, and the histamine response was mediated by phosphoinositide
      specific phospholipase C and PKC-delta in human umbilical vein endothelial cells.

PMID- 14975704
TI  - Enhanced antidepressant efficacy of sigma1 receptor agonists in rats after
      chronic intracerebroventricular infusion of beta-amyloid-(1-40) protein.
AB  - Treatment of depressive symptoms in patients suffering from neurodegenerative
      disorders remains a challenging issue, since few available antidepressants
      present an adequate efficacy during pathological aging. Previous reports
      suggested that selective sigma(1) receptor agonists might constitute putative
      candidates. We here examined the pharmacological efficacy of igmesine and (+)-SKF
      10,047 and the sigma(1) receptor-related neuroactive steroid
      dehydroepiandrosterone sulfate, in rats infused intracerebroventricularly during
      14 days with the beta-amyloid-(1-40) protein and then submitted to the
      conditioned fear stress test. Igmesine and (+)-SKF-10,047 significantly reduced
      the stress-induced motor suppression at 30 and 6 mg/kg, respectively, in beta
      amyloid-(40-1)-treated control rats. Active doses were decreased, to 10 and 3
      mg/kg, respectively, in beta-amyloid-(1-40)-treated animals. The
      dehydroepiandrosterone sulfate effect was also facilitated, both in dose (10 vs.
      30 mg/kg) and intensity, in beta-amyloid-(1-40)-treated rats. Neurosteroid levels
      were measured in several brain structures after beta-amyloid infusion, in basal
      and stress conditions. Progesterone levels, both under basal and stress-induced
      conditions, were decreased in the hippocampus and cortex of beta-amyloid-(1-40)
      treated rats. The levels in pregnenolone, dehydroepiandrosterone and their
      sulfate esters appeared less affected by the beta-amyloid infusion. The sigma(1)
      receptor agonist efficacy is known to be inversely correlated to brain
      progesterone levels, synthesized mainly by neurons that are mainly affected by
      the beta-amyloid toxicity. The present study suggests that sigma(1) receptor
      agonists, due to their enhanced efficacy in a nontransgenic animal model, may
      alleviate Alzheimer's disease-associated depressive symptoms.

PMID- 14975705
TI  - Neurotrophic actions of the novel AMPA receptor potentiator, LY404187, in rodent
      models of Parkinson's disease.
AB  - Recent developments in the molecular biology and pharmacology of alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors has led to the
      discovery of selective, potent and systemically active AMPA receptor
      potentiators. These molecules enhance synaptic transmission and evidence suggests
      that they play important roles in plasticity and cognitive processes. Activation
      of AMPA receptors also increases neuronal activation and activity-dependent
      signalling, which may increase brain-derived neurotrophic factor (BDNF)
      expression and enhance cell proliferation in the brain. We therefore hypothesised
      that an AMPA receptor potentiator may provide neurotrophic effects in rodent
      models of Parkinson's disease. In the present studies we report that the potent
      and selective AMPA receptor potentiator, R,S-N-2-(4-(4-Cyanophenyl)phenyl)propyl
      2-propanesulfonamide (LY404187), provides both functional, neurochemical and
      histological protection against unilateral infusion of 6-hydroxydopamine into the
      substantia nigra or striatum of rats. The compound also reduced 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in mice. Interestingly, we
      were also able to observe large functional and histological effects when we
      delayed treatment until after cell death had occurred (3 or 6 days after 6
      hydroxydopamine infusion), supporting a neurotrophic mechanism of action. In
      addition, LY404187 provided a dose-dependent increase in growth-associated
      protein-43 expression in the striatum. Therefore, we propose that AMPA receptor
      potentiators offer the potential of a new therapy to halt the progression and
      perhaps repair the degeneration in Parkinson's disease.

PMID- 14975706
TI  - Nicotine-antipsychotic drug interactions and attentional performance in female
      rats.
AB  - Schizophrenia is marked by pronounced cognitive impairments in addition to the
      hallmark psychotic symptoms like hallucinations. Antipsychotic drugs can
      effectively reduce these hallucinations; however, the drugs have not resolved the
      cognitive impairment. Interestingly, nicotine, a drug commonly self-administered
      by people with schizophrenia, has been shown to significantly improve cognitive
      function of people with schizophrenia. The current study was conducted to
      determine the effect of typical (haloperidol) and atypical (clozapine and
      risperidone) antipsychotic drug treatment on sustained attention in rats
      performing a visual signal detection task. In addition, the interaction of
      haloperidol with chronic nicotine administration was assessed. Female Sprague
      Dawley rats were injected subcutaneously with clozapine (0, 0.6, 1.25 and 2.5
      mg/kg), risperidone (0, 0.025, 0.05 and 0.1 mg/kg) or haloperidol (0, 0.01, 0.02
      and 0.04 mg/kg). In the second part of the study, the interaction of acute
      haloperidol (0, 0.005, 0.01 and 0.02 mg/kg) and chronic nicotine (5 mg/kg/day,
      for 4 weeks via osmotic minipump) was characterized. Clozapine, risperidone and
      haloperidol all caused dose-related impairments in percent hit performance. There
      was a significant linear dose-related impairment in percent hit caused by
      risperidone. All the doses of clozapine caused a significant impairment in
      percent hit at the higher luminance intensities in the visual signal detection
      task. The 0.01 and 0.02 mg/kg haloperidol doses caused significant decreases in
      percent hit. The 0.04 mg/kg haloperidol dose impaired performance of the task to
      the point that reliable choice accuracy measurements could not be made. Chronic
      nicotine infusion significantly diminished the impairing effects of haloperidol
      on performance during weeks 1-2. In summary, both typical and atypical
      antipsychotic drugs significantly impaired sustained attention in rats.
      Haloperidol was more detrimental than clozapine and risperidone. Chronic nicotine
      diminished the adverse effects of haloperidol on performance. This study
      establishes a paradigm to reliably determine the attentional impairment caused by
      antipsychotic drugs.

PMID- 14975707
TI  - Pre-weaning carvedilol treatment in spontaneously hypertensive rats.
AB  - Hypertension in spontaneously hypertensive rats (SHR) has been permanently
      abolished by aggressive treatment regimens targeted against the sympathetic
      nervous system and adrenal medulla, initiated during the pre-weaning period
      (guanethidine and nerve growth factor antiserum combined with either adrenal
      demedullation or prazosin treatment). To investigate the components of the
      sympatho-adrenal system involved, we treated pre-weaning SHR with the combined
      alpha(1)- and beta-adrenoceptor antagonist carvedilol (60 mg/kg/day s.c.;
      postnatal days 1-21). Carvedilol treatment significantly blocked adrenoceptors
      during the treatment period, delayed development (eye opening), reduced growth,
      and reduced arterial pressure and heart rate. However, there was only modest
      attenuation of the subsequent development of hypertension at 10 weeks of age
      (mean arterial pressure 129.5+/-1.8 versus 136.1+/-1.6 mm Hg in vehicle-treated
      littermates; P<0.05). Thus pre-weaning carvedilol treatment slightly but
      significantly attenuated the development of SHR hypertension at 10 weeks,
      suggesting that the profound antihypertensive effects of pre-weaning sympatho
      adrenal ablation are attributable to factors other than alpha(1)- and beta
      adrenoceptor-mediated effects of catecholamines during this period.

PMID- 14975708
TI  - In vivo experimental approach for the risk assessment of fluoroquinolone
      antibacterial agents-induced long QT syndrome.
AB  - The proarrhythmic effects of fluoroquinolone antibacterial agents, sitafloxacin,
      gatifloxacin and moxifloxacin, were compared using three in vivo models. In the
      halothane-anesthetized dogs (n=5), intravenous 10-min infusion of gatifloxacin
      and moxifloxacin (1-3 mg/kg) prolonged the ventricular effective refractory
      period and the repolarization period to a similar extent, whereas sitafloxacin (1
      3 mg/kg) prolonged the former only. No significant change was detected in other
      cardiovascular parameters. In the chronic complete atrioventricular block dogs
      (n=4), oral administration of 100 mg/kg of gatifloxacin (2 of 4) and moxifloxacin
      (3 of 4) induced torsades de pointes, which was not observed by sitafloxacin. In
      the alpha-chloralose-anesthetized rabbits (n=5), intravenous 20-min infusion of
      60 mg/kg of gatifloxacin induced torsades de pointes (1 of 5) in the presence of
      methoxamine infusion, which was not observed by sitafloxacin or moxifloxacin.
      Thus, the halothane-anesthetized model is suitable for assessing QT prolongation,
      whereas the chronic complete atrioventricular block model is sensitive for
      detecting torsadogenic action of drugs. The alpha-chloralose-anesthetized model
      is the simplest and least expensive method, but its sensitivity to detect
      proarrhythmic action may be less great.

PMID- 14975709
TI  - Influence of the endothelium on ex vivo tolerance and metabolism of glyceryl
      trinitrate in rat aorta.
AB  - The influence of the endothelium on glyceryl trinitrate metabolism and relaxation
      and the relationship to tolerance induced by transdermal glyceryl trinitrate was
      explored in rat aorta. Metabolism was assessed in artery segments incubated with
      glyceryl trinitrate (1.0 microM) for 2 min and the contents of 1,2- and 1,3
      glyceryl dinitrate measured by gas chromatography. In non-tolerant arteries mean
      contents of glyceryl trinitrate, 1,2-glyceryl dinitrate and 1,3-glyceryl
      dinitrate were 3.2, 0.23 and 0.10 nmol/g, respectively; in tolerant arteries the
      content of 1,2-glyceryl dinitrate was reduced by approximately 60%. Endothelium
      removal or nitric oxide synthase (NOS) inhibition did not affect metabolite
      contents but increased the relaxant response to glyceryl trinitrate in the
      tolerant artery to an extent that tolerance was significantly attenuated. It is
      concluded that (i) tolerance is associated with depression of glyceryl trinitrate
      metabolism by an endothelium-independent mechanism and (ii) the endothelium
      contributes to tolerance by a mechanism which is independent of metabolism and
      may be linked with endothelial NOS.

PMID- 14975710
TI  - Differential effect of HERG blocking agents on cardiac electrical alternans in
      the guinea pig.
AB  - Beat-to-beat alternations of the cardiac monophasic action potential, known as
      electrical alternans, were studied at drug concentrations that have known
      arrhythmogenic outcomes. Electrical alternans were elicited from the heart of
      anesthetized guinea pigs, both in the absence and presence of drugs that inhibit
      the delayed rectifier K(+) channel encoded by the human ether a-go-go related
      gene (HERG), and are associated with the fatal arrhythmia, Torsade de Pointes.
      Two other HERG inhibiting drugs not associated with Torsade de Pointes were also
      studied. At concentrations known to be proarrhythmic, E-4031 and bepridil
      increased mean alternans 10 and 40 ms at pacing frequencies </=160 ms.
      Terfenadine and cisapride both increased mean alternans up to 20 and 21 ms,
      respectively, at pacing frequencies of </=150 ms. On the other hand, verapamil
      and risperidone showed no increase in mean alternans while risperidone
      significantly reduced alternans at concentrations up to 74 times its therapeutic
      level. The magnitude of effect on rate-dependent alternans may allow the
      differentiation of proarrhythmia and non-arrhythmic HERG blockers at clinically
      relevant concentrations.

PMID- 14975711
TI  - Influence of polyethylene-glycol-superoxide dismutase and combined depletion and
      repletion of antioxidants on nitrergic relaxation in the pig gastric fundus.
AB  - In circular smooth muscle strips of porcine gastric fundus, polyethylene-glycol
      superoxide dismutase, a membrane-permeable analogue of endogenous copper/zinc
      (Cu/Zn) superoxide dismutase, reversed the inhibitory effect of the superoxide
      anion generator 6-anilino-5,8-quinolinedione (LY83583) on electrically induced
      nitrergic relaxations of fundic tissues which are depleted of the endogenous
      antioxidant Cu/Zn superoxide dismutase by diethyldithiocarbamate, to the same
      extent as exogenously added Cu/Zn superoxide dismutase. Addition of a second
      antioxidant together with Cu/Zn superoxide dismutase does not result in a higher
      degree of reversal of the inhibitory effect of LY83583. Depletion of either
      tissue glutathione or tissue catalase in combination with diethyldithiocarbamate
      does not increase the inhibitory action of LY83583 or the nitric oxide (NO)
      scavenger hydroxocobalamin upon nitrergic relaxations (electrically induced or by
      exogenous NO) when compared to their action in the presence of
      diethyldithiocarbamate alone. In conclusion, these results demonstrate that
      endogenous Cu/Zn superoxide dismutase is the essential antioxidant responsible
      for safeguarding peripheral nitrergic neurotransmission, whereby extracellular
      protection of endogenous NO is most important.

PMID- 14975712
TI  - Endogenous ligands of PPAR-gamma reduce the liver injury in haemorrhagic shock.
AB  - We demonstrate here for the first time that the novel, potent peroxisome
      proliferator-activated receptor (PPAR)-gamma antagonist GW9662 (2-chloro-5
      nitrobenzanilide) augments the degree of liver injury associated with
      haemorrhagic (haemorrhage for 90 min and resuscitation for 4 h), but not
      endotoxic (6 mg/kg E. coli endotoxin i.v. for 6 h) shock in the anaesthetised
      rat. Thus, endogenous ligands for PPAR-gamma are released in haemorrhagic, but
      not endotoxic, shock in sufficient amounts to protect against injury.

PMID- 14975713
TI  - Maintenance of meiotic prophase arrest in vertebrate oocytes by a Gs protein
      mediated pathway.
AB  - Maintenance of meiotic prophase arrest in fully grown vertebrate oocytes depends
      on an elevated level of cAMP in the oocyte. To investigate how the cAMP level is
      regulated, we examined whether the activity of an oocyte G protein of the family
      that stimulates adenylyl cyclase, Gs, is required to maintain meiotic arrest.
      Microinjection of a dominant negative form of Gs into Xenopus and mouse oocytes,
      or microinjection of an antibody that inhibits the Gs G protein into zebrafish
      oocytes, caused meiosis to resume. Together with previous studies, these results
      support the conclusion that Gs-regulated generation of cAMP by the oocyte is a
      common mechanism for maintaining meiotic prophase arrest in vertebrate oocytes.

PMID- 14975715
TI  - Developmental switch in axon guidance modes of hippocampal mossy fibers in vitro.
AB  - Hippocampal mossy fibers (MFs), axons of dentate granule cells, run through a
      narrow strip, called the stratum lucidum, and make synaptic contacts with CA3
      pyramidal cells. This stereotyped pathfinding is assumed to require a tightly
      controlled guidance system, but the responsible mechanisms have not been proven
      directly. To clarify the cellular basis for the MF pathfinding, microslices of
      the dentate gyrus (DG) and Ammon's horn (AH) were topographically arranged in an
      organotypic explant coculture system. When collagen gels were interposed between
      DG and AH slices prepared from postnatal day 6 (P6) rats, the MFs passed across
      this intervening gap and reached CA3 stratum lucidum. Even when the recipient AH
      was chemically pre-fixed with paraformaldehyde, the axons were still capable of
      accessing their normal target area only if the DG and AH slices were directly
      juxtaposed without a collagen bridge. The data imply that diffusible and contact
      cues are both involved in MF guidance. To determine how these different cues
      contribute to MF pathfinding during development, a P6 DG slice was apposed
      simultaneously to two AH slices prepared from P0 and P13 rats. MFs projected
      normally to both the host slices, whereas they rarely invaded P0 AH when the two
      hosts were fixed. Early in development, therefore, the MFs are guided mainly by a
      chemoattractant gradient, and thereafter, they can find their trajectories by a
      contact factor, probably via fasciculation with pre-established MFs. The present
      study proposes a dynamic paradigm in CNS axon pathfinding, that is, developmental
      changes in axon guidance cues.

PMID- 14975714
TI  - Essential roles of Meltrin beta (ADAM19) in heart development.
AB  - Morphogenesis of the heart requires development of the endocardial cushion tissue
      that gives rise to the membranous septa and valves. Here we show that Meltrin
      beta/ADAM19, a novel metalloprotease-disintegrin, participates in the development
      of the endocardial cushion. Mice lacking Meltrin beta exhibit ventricular septal
      defect (VSD) and immature valves, and most of the animals die soon after birth.
      During development of the endocardial cushion, epithelial-mesenchymal
      transformation (EMT) of endocardial epithelial cells generates most of the
      cushion mesenchymes that constitute the main components of the septa and valves.
      Meltrin beta is expressed in both the epithelia and the mesenchymes of the
      endocardial cushion. In the absence of Meltrin beta, the cushion is small or thin
      in the septum-forming region and show poor remodeling of cardiac jelly
      components; both of these characteristics suggest impaired growth and
      differentiation of the endocardial cushion. When embryonic fibroblasts are
      cultured sparsely, Meltrin beta-lacking cells exhibit aberrant ectodomain
      shedding of type I Neuregulin, one of the ErbB ligands expressed in endocardial
      cells. These results suggest the necessity of proteolytic regulation of ErbB
      ligands by Meltrin beta for proper heart development.

PMID- 14975716
TI  - HyBMP5-8b, a BMP5-8 orthologue, acts during axial patterning and tentacle
      formation in hydra.
AB  - Developmental gradients play a central role in axial patterning in hydra. As part
      of the effort towards elucidating the molecular basis of these gradients as well
      as investigating the evolution of the mechanisms underlying axial patterning,
      genes encoding signaling molecules are under investigation. We report the
      isolation and characterization of HyBMP5-8b, a BMP5-8 orthologue, from hydra.
      Processes governing axial patterning are continuously active in adult hydra.
      Expression patterns of HyBMP5-8b in normal animals and during bud formation,
      hydra's asexual form of reproduction, were examined. These patterns, coupled with
      changes in patterns of expression in manipulated tissues during head
      regeneration, foot regeneration as well as under conditions that alter the
      positional value gradient indicate that the gene is active in two different
      processes. The gene plays a role in tentacle formation and in patterning the
      lower end of the body axis.

PMID- 14975717
TI  - Hermes is a localized factor regulating cleavage of vegetal blastomeres in
      Xenopus laevis.
AB  - We have identified the RNA-binding protein Hermes in a screen for vegetally
      localized RNAs in Xenopus oocytes. The RNA localizes to the vegetal cortex
      through both the message transport organizer (METRO) and late pathways. Hermes
      mRNA and protein are both detected at the vegetal cortex of the oocyte; however,
      the protein is degraded within a several hour period during oocyte maturation.
      Injection of antisense morpholino oligonucleotides (HE-MO) against Hermes caused
      a precocious reduction in Hermes protein present during maturation and resulted
      in a phenotype characterized by cleavage defects in vegetal blastomeres. The
      phenotype can be partially rescued by injecting Hermes mRNA. These results
      demonstrate that the localized RNA-binding protein Hermes functions during oocyte
      maturation to regulate the cleavage of specific vegetally derived cell lineages.
      Hermes most likely performs its function by regulating the translation or
      processing of one or more target RNAs. This is an important mechanism by which
      the embryo can generate unique cell lineages. The regulation of region-specific
      cell division is a novel function for a localized mRNA.

PMID- 14975718
TI  - Frontonasal process-specific disruption of AP-2alpha results in postnatal
      midfacial hypoplasia, vascular anomalies, and nasal cavity defects.
AB  - A majority of the bones of the vertebrate cranial vault and craniofacial complex
      develop via intramembranous ossification, and are separated by fibrous sutures
      that undergo osteogenic differentiation in response to growth stimuli.
      Craniosynostosis is a common human birth defect that results from the premature
      bony fusion within skull sutures, and causes a myriad of complications including
      mental retardation and craniofacial anomalies. Synostosis of facial sutures has
      been reported to cause midfacial hypoplasia in some craniosynostosis cases, but
      most studies focus on cranial vault sutures. In this study, we have generated a
      mouse model of frontonasal suture synostosis and midfacial hypoplasia through the
      tissue-specific elimination of the AP-2alpha transcription factor. We report here
      the generation AP-2CRE, a frontonasal process (FNP)- and limb-specific CRE
      recombinase allele that is directed by human AP-2alpha promoter and enhancer
      elements. We used the AP-2CRE line in combination with the conditional AP-2alpha
      line to produce a new frontonasal knockout (FKO) mutant that lacks AP-2alpha in
      the FNP and limbs. FKO mice exhibit shortened snouts and wide-set eyes that
      become apparent at postnatal day 15. The most prominent defects in FKO snouts are
      (1) a lack of growth within the frontonasal sutures, and (2) a reduction in the
      snout vasculature. Additional defects are observed in the FKO nasal bones and
      sutures, the nasal cavity cartilage and bony projections, and the olfactory
      epithelium. The characteristics of the FKO mouse model are a unique combination
      of midfacial growth anomalies, and provide the first evidence that AP-2alpha is
      essential for appropriate postnatal craniofacial morphogenesis.

PMID- 14975719
TI  - PITX2 is required for normal development of neurons in the mouse subthalamic
      nucleus and midbrain.
AB  - Pitx2, a homeodomain transcription factor, is essential for normal development of
      the pituitary gland, craniofacial region, eyes, heart, abdominal viscera, and
      limbs. Complete loss of Pitx2 in mice (Pitx2(-/-)) results in embryonic lethality
      by approximately e15 due to cardiac defects, whereas embryos with partial loss of
      function (Pitx2(neo/-) or Pitx2(neo/neo)) survive until later in development (e17
      e19). Pitx2 is expressed in discrete populations of postmitotic neurons in the
      mouse brain, but its role in mammalian central nervous system (CNS) development
      is not known. We undertook an analysis of Pitx2-deficient embryos to determine
      whether loss of Pitx2 affects CNS development. The CNS is normal in hypomorphic
      e16.5 Pitx2(neo/-) and e18.5 Pitx2(neo/neo) embryos, with no evidence of midline
      or other defects. Midgestation (e10.5) Pitx2(-/-) embryos have normally formed
      neural tube structures and cerebral vesicles, whereas older (e14.5) Pitx2(-/-)
      embryos exhibit loss of gene expression and axonal projections in the subthalamic
      nucleus (a group of cells in the ventrolateral thalamus) and in the developing
      superior colliculus of dorsal midbrain. Our results suggest a role for Pitx2 in
      regulating regionally specific terminal neuronal differentiation in the
      developing ventrolateral thalamus and midbrain.

PMID- 14975720
TI  - Widespread tangential dispersion and extensive cell death during early
      neurogenesis in the mouse neocortex.
AB  - The development of the mammalian neocortex requires radial and tangential
      migration of cells. Radial migration of differentiated neurons from the
      ventricular zone (VZ) is well established. It is hypothesised that an earlier
      phase of tangential migration of mitotically active cells lays down a widespread
      periodically spaced set of progenitors that generate radial arrays of postmitotic
      neurons. We use a transgenic cell lineage marker to label and observe the
      behaviour of progenitors before and during the early stages of neurogenesis.
      Using optical projection tomography (OPT), we show that individual progenitor
      cells generate many radially arrayed columns of periodically spaced cells. Column
      positions indicate the paths taken by these progenitor cells as they migrate,
      often over long distances, through the proliferative zone. Clonally related cells
      can be distributed in both hemispheres, suggesting progenitor cells cross the
      midline in the anterior neural plate. We observe a dramatic and rapid decline in
      the number of labelled clones after E13.5, indicating that there is extensive
      cell death at this time.

PMID- 14975721
TI  - FGF signaling is required for determination of otic neuroblasts in the chick
      embryo.
AB  - The interplay between intrinsic and extrinsic factors is essential for the
      transit into different cell states during development. We have analyzed the
      expression and function of FGF10 and FGF-signaling during the early stages of the
      development of otic neurons. FGF10 is expressed in a highly restricted domain
      overlapping the presumptive neurogenic region of the chick otic placode. A
      detailed study of the expression pattern of FGF10, proneural, and neurogenic
      genes revealed the following temporal sequence for the onset of gene expression:
      FGF10>Ngn1/Delta1/Hes5>NeuroD/NeuroM. FGF10 and FGF receptor inhibition cause
      opposed effects on cell determination and cell proliferation. Ectopic expression
      of FGF10 in vivo promotes an increase in NeuroD and NeuroM expression. BrdU
      incorporation experiments showed that the increase in NeuroD-expressing cells is
      not due to an increase in cell proliferation. Inhibition of FGF receptor
      signaling in otic explants causes a severe reduction in Neurogenin1, NeuroD,
      Delta1, and Hes5 expression with no change in non-neural genes like Lmx1.
      However, it does not interfere with NeuroD expression within the CVG or with
      neuroblast delamination. The loss of proneural gene expression caused by FGF
      inhibition is not caused by decreased cell proliferation or by increased cell
      death. We suggest that FGF signaling in the otic epithelium is required for
      neuronal precursors to withdraw from cell division and irreversibly commit to
      neuronal fate.

PMID- 14975722
TI  - Wnt1-Cre-mediated deletion of AP-2alpha causes multiple neural crest-related
      defects.
AB  - The AP-2alpha transcription factor is required for multiple aspects of vertebrate
      development and mice lacking the AP-2alpha gene (tcfap2a) die at birth from
      severe defects affecting the head and trunk. Several of the defects associated
      with the tcfap2a-null mutation affect neural crest cell (NCC) derivatives
      including the craniofacial skeleton, cranial ganglia, and heart outflow tract.
      Consequently, there is considerable interest in the role of AP-2alpha in neural
      crest cell function in development and evolution. In addition, the expression of
      the AP-2alpha gene is utilized as a marker for premigratory and migratory neural
      crest cells in many vertebrate species. Here, we have specifically addressed how
      the presence of AP-2alpha in neural crest cells affects development by creating a
      conditional (floxed) version of tcfap2a which has subsequently been intercrossed
      with mice expressing Cre recombinase under the control of Wnt1 cis-regulatory
      sequences. Neural crest-specific disruption of tcfap2a results in frequent
      perinatal lethality associated with neural tube closure defects and cleft
      secondary palate. A small but significant fraction of mutant mice can survive
      into adulthood, but have retarded craniofacial growth, abnormal middle ear
      development, and defects in pigmentation. The phenotypes obtained confirm that AP
      2alpha directs important aspects of neural crest cell function. At the same time,
      we did not observe several neurocristopathies affecting the head and heart that
      might be expected based on the phenotype of the AP-2alpha-null mouse. These
      results have important implications for the evolution and function of the AP-2
      gene family in both the neural crest and the vertebrate embryo.

PMID- 14975723
TI  - Temporal regulation of cerebellar EGL migration through a switch in cellular
      responsiveness to the meninges.
AB  - We have studied the temporal and spatial control of cell migration from the
      external germinal layer (EGL) in the mammalian cerebellum as a model for cortical
      migration. Our results have demonstrated that embryonic EGL cells do not migrate
      into internal layers because they respond to a diffusible attractant in the
      meninges, the nonneural tissues covering the nervous system, and to a repellent
      in the neuroepithelium. Two developmental changes are important for postnatal EGL
      migration: the disappearance of the repellent in the inner layers and a switch in
      cellular responsiveness of EGL cells so that the postnatal EGL cells respond to
      the repellent, but not the attractant in the meninges. Besides revealing the
      signaling role of meninges in cortical development, our study suggests that an
      active mechanism is required to prevent cell migration, and that mechanisms of
      cell migration should be studied even in the absence of apparent changes in cell
      positions. We propose a model for the developmental control of neuronal migration
      in the cerebellar cortex.

PMID- 14975724
TI  - Sequential antagonism of early and late Wnt-signaling by zebrafish colgate
      promotes dorsal and anterior fates.
AB  - The establishment of the vertebrate body plan involves patterning of the
      ectoderm, mesoderm, and endoderm along the dorsoventral and antero-posterior
      axes. Interactions among numerous signaling molecules from several multigene
      families, including Wnts, have been implicated in regulating these processes.
      Here we provide evidence that the zebrafish colgate(b382) (col) mutation results
      in increased Wnt signaling that leads to defects in dorsal and anterior
      development. col mutants display early defects in dorsoventral patterning
      manifested by a decrease in the expression of dorsal shield-specific markers and
      ectopic expression of ventrolaterally expressed genes during gastrulation. In
      addition to these early patterning defects, col mutants display a striking
      regional posteriorization within the neuroectoderm, resulting in a reduction in
      anterior fates and an expansion of posterior fates within the forebrain and
      midbrain-hindbrain regions. We are able to correlate these phenotypes to the
      overactivation of Wnt signaling in col mutants. The early dorsal and anterior
      patterning phenotypes of the col mutant embryos are selectively rescued by
      inactivation of Wnt8 function by morpholino translational interference. In
      contrast, the regionalized neuroectoderm posterioriorization phenotype is
      selectively rescued by morpholino-mediated inactivation of Wnt8b. These results
      suggest that col-mediated antagonism of early and late Wnt-signaling activity
      during gastrulation is normally required sequentially for both early dorsoventral
      patterning and the specification and patterning of regional fates within the
      anterior neuroectoderm.

PMID- 14975725
TI  - Cooperation of JAK/STAT and Notch signaling in the Drosophila foregut.
AB  - Temporal and spatial regulation of morphogenesis is pivotal to the formation of
      organs from simple epithelial tubes. In a genetic screen for novel genes
      controlling cell movement during posterior foregut development, we have
      identified and molecularly characterized two alleles of the domeless gene which
      encodes the Drosophila Janus kinase (JAK)/STAT receptor. We demonstrate that
      mutants for domeless or any other known component of the canonical JAK/STAT
      signaling pathway display a failure of coordinated cell movement during the
      development of the proventriculus, a multiply folded organ which is formed by
      stereotyped cell rearrangements in the posterior foregut. Whereas the JAK/STAT
      receptor is expressed in all proventricular precursor cells, expression of upd
      encoding its ligand and of STAT92E, the signal transducer of the pathway, is
      locally restricted to cells that invaginate during proventriculus development. We
      demonstrate by analyzing gene expression mediated by a model Notch response
      element and by studying the expression of the Notch target gene short stop, which
      encodes a cytoskeletal crosslinker protein, that JAK/STAT signaling is required
      for the activation of Notch-dependent gene expression in the foregut. Our results
      provide strong evidence that JAK/STAT and Notch signaling cooperate in the
      regulation of target genes that control epithelial morphogenesis in the foregut.

PMID- 14975726
TI  - Cre-mediated excision of Fgf8 in the Tbx1 expression domain reveals a critical
      role for Fgf8 in cardiovascular development in the mouse.
AB  - Tbx1 has been implicated as a candidate gene responsible for defective pharyngeal
      arch remodeling in DiGeorge/Velocardiofacial syndrome. Tbx1(+/-) mice mimic
      aspects of the DiGeorge phenotype with variable penetrance, and null mice display
      severe pharyngeal hypoplasia. Here, we identify enhancer elements in the Tbx1
      gene that are conserved through evolution and mediate tissue-specific expression.
      We describe the generation of transgenic mice that utilize these enhancer
      elements to direct Cre recombinase expression in endogenous Tbx1 expression
      domains. We use these Tbx1-Cre mice to fate map Tbx1-expressing precursors and
      identify broad regions of mesoderm, including early cardiac mesoderm, which are
      derived from Tbx1-expressing cells. We test the hypothesis that fibroblast growth
      factor 8 (Fgf8) functions downstream of Tbx1 by performing tissue-specific
      inactivation of Fgf8 using Tbx1-Cre mice. Resulting newborn mice display DiGeorge
      like congenital cardiovascular defects that involve the outflow tract of the
      heart. Vascular smooth muscle differentiation in the great vessels is disrupted.
      This data is consistent with a model in which Tbx1 induces Fgf8 expression in the
      pharyngeal endoderm, which is subsequently required for normal cardiovascular
      morphogenesis and smooth muscle differentiation in the aorta and pulmonary
      artery.

PMID- 14975727
TI  - A novel aminophospholipid transporter exclusively expressed in spermatozoa is
      required for membrane lipid asymmetry and normal fertilization.
AB  - Through the use of a functionally unbiased signal peptide trap screen, we have
      discovered an ATP-dependent aminophospholipid transporter that is exclusively
      expressed in the acrosomal region of spermatozoa; it is about 62% similar to the
      flippase, FIC1. We disrupted the transporter gene and found that the size of
      litters from male null mice was slightly smaller than found with wild-type males.
      Sperm morphology and motility were the same between null and wild-type
      littermates, but agents (merocyanine and annexin) that measure phospholipid
      packing or phosphatidylserine (PS) in the outer membrane leaflet showed that PS
      already existed in the outer leaflet of null spermatozoa before sperm
      capacitation. Fertilization rates were normal when null spermatozoa were added to
      zona pellucida-free eggs, but in the presence of the extracellular matrix, fewer
      transporter(-/-) spermatozoa bound tightly or penetrated the zona pellucida (ZP),
      and fewer underwent acrosome reactions. In vitro fertilization was compromised,
      especially at early time points or at low sperm concentrations after mixing null
      spermatozoa and eggs. Thus, a new aminophospholipid transporter expressed
      exclusively in spermatozoa is critical for normal phospholipid distribution in
      the bilayer, and for normal binding, penetration, and signaling by the zona
      pellucida.

PMID- 14975728
TI  - Intermediate filaments are required for C. elegans epidermal elongation.
AB  - Cytoplasmic intermediate filaments (cIFs) are thought to provide mechanical
      strength to vertebrate cells; however, their function in invertebrates has been
      largely unexplored. The Caenorhabditis elegans genome encodes multiple cIFs. The
      C. elegans ifb-1 locus encodes two cIF isoforms, IFB-1A and IFB-1B, that differ
      in their head domains. We show that both IFB-1 isoforms are expressed in
      epidermal cells, within which they are localized to muscle-epidermal attachment
      structures. Reduction in IFB-1A function by mutation or RNA interference (RNAi)
      causes epidermal fragility, abnormal epidermal morphogenesis, and muscle
      detachment, consistent with IFB-1A providing mechanical strength to epidermal
      attachment structures. Reduction in IFB-1B function causes morphogenetic defects
      and defective outgrowth of the excretory cell. Reduction in function of both IFB
      1 isoforms results in embryonic arrest due to muscle detachment and failure in
      epidermal cell elongation at the 2-fold stage. Two other cIFs, IFA-2 and IFA-3,
      are expressed in epidermal cells. We show that loss of function in IFA-3 results
      in defects in morphogenesis indistinguishable from those of embryos lacking ifb
      1. In contrast, IFA-2 is not required for embryonic morphogenesis. Our data
      indicate that IFB-1 and IFA-3 are likely the major cIF isoforms in embryonic
      epidermal attachment structures.

PMID- 14975729
TI  - Crosstalk between protein kinase A and C regulates phospholipase D and F-actin
      formation during sperm capacitation.
AB  - Mammalian spermatozoa should reside in the female reproductive tract for a
      certain time before gaining the ability to fertilize. During this time, the
      spermatozoa undergo a series of biochemical processes collectively called
      capacitation. We recently demonstrated that actin polymerization is a necessary
      step in the cascade leading to capacitation. We demonstrate here for the first
      time a role for phospholipase D (PLD) in the induction of actin polymerization
      and capacitation in spermatozoa. The involvement of PLD is supported by specific
      inhibition of F-actin formation during sperm capacitation by PLD inhibitors and
      the stimulation of fast F-actin formation by exogenous PLD or phosphatidic acid
      (PA). Moreover, PLD activity is enhanced during capacitation before actin
      polymerization. Protein kinase A (PKA), known to be active in sperm capacitation,
      and protein kinase C (PKC), involved in the acrosome reaction, can both activate
      PLD and actin polymerization. We suggest that PKA- and PKC-dependent signal
      transduction pathways can potentially lead to PLD activation; however, under
      physiological conditions, actin polymerization depends primarily on PKA activity.
      Activation of PKA during capacitation causes inactivation of phospholipase C, and
      as a result, PKC activation is prevented. It appears that PKA activation promotes
      sperm capacitation whereas early activation of PKC during capacitation would
      jeopardize this process.

PMID- 14975730
TI  - A role for Noggin in the development of oligodendrocyte precursor cells.
AB  - Oligodendrocyte precursor cells (OPCs) can be differentiated in culture into
      either oligodendrocytes or type-2 astrocytes (2As), depending on the culture
      conditions. Whereas oligodendrocyte development can occur in the absence of
      inducing signals, 2A development apparently cannot. Fetal calf serum (FCS) and
      bone morphogenetic proteins (BMPs) are powerful inducers of 2A development in
      culture, but there is no compelling evidence that OPCs develop into astrocytes in
      vivo. We show here that BMPs are made by glial cells in the developing rat optic
      nerve, raising the question of why 2As do not normally develop in the optic
      nerve. We demonstrate that the BMP antagonist Noggin is strongly expressed by
      both OPCs and type-1 astrocytes in the developing optic nerve. We also show that
      depletion of Noggin by a small interference RNA inhibits OPC proliferation and
      induces 2A differentiation in the presence of a low, non-2A-inducing
      concentration of FCS. By contrast, enforced expression of Noggin in OPCs blocks
      FCS-induced 2A differentiation. These findings suggest that BMPs in FCS are
      largely responsible for the 2A-inducing activity of FCS and that Noggin may
      normally inhibit the formation of 2As in the developing CNS.

PMID- 14975731
TI  - The nT1 translocation separates vulval regulatory elements from the egl-18 and
      elt-6 GATA factor genes.
AB  - egl-18 and elt-6 are partially redundant, adjacent genes encoding GATA factors
      essential for viability, seam cell development, and vulval development in
      Caenorhabditis elegans. The nT1 reciprocal translocation causes a strong
      Vulvaless phenotype, and an nT1 breakpoint was previously mapped to the left arm
      of LGIV, where egl-18/elt-6 are located. Here we present evidence that the nT1
      vulval phenotype is due to a disruption of egl-18/elt-6 function specifically in
      the vulva. egl-18 mutations do not complement nT1 for vulval defects, and the nT1
      breakpoint on LGIV is located within approximately 800 bp upstream of a potential
      transcriptional start site of egl-18. In addition, we have identified a
      approximately 350-bp cis-regulatory region sufficient for vulval expression just
      upstream of the nT1 breakpoint. By examining the fusion state and division
      patterns of the cells in the developing vulva of nT1 mutants, we demonstrate that
      egl-18/elt-6 prevent fusion and promote cell proliferation at multiple steps of
      vulval development.

PMID- 14975732
TI  - Characterization and identification of the inhibitory domain of GDF-8 propeptide.
AB  - GDF-8 is a negative regulator of skeletal muscle mass. The mechanisms which
      regulate the biological activity of GDF-8 have not yet been elucidated. Analogous
      to the TGF-beta system, GDF-8 propeptide binds to and inhibits the activity of
      GDF-8. In these studies, we define the critical domain of the GDF-8 propeptide
      necessary for inhibitory activity. Two molecules of GDF-8 propeptide monomer
      inhibit the biological activity of one molecule of GDF-8 homodimer. Although the
      propeptide contains N-linked glycosylation when synthesized in mammalian cells,
      this glycosylation is not necessary for the inhibition of GDF-8. Taking advantage
      of the bacterial expression system, we express and purify GDF-8 propeptide which
      retains full inhibitory activity. To define the functional regions of the
      propeptide, we express a series of truncated GST-propeptide fusion proteins and
      examined their inhibitory activity. We observe that fusion proteins containing
      the C-terminal region (amino acid residues 99-266) are very stable, but do not
      exhibit inhibitory activity; while fusion proteins containing the N-terminal
      region (amino acid residues 42-115) are labile but contain essential inhibitory
      activity. The data suggest that the C-terminal region may play a role in the
      stability of the GDF-8 propeptide and that the inhibitory domain is located in
      the region between amino acids 42 and 115.

PMID- 14975733
TI  - Evidence that the anti-obesity effect of conjugated linoleic acid is independent
      of effects on stearoyl-CoA desaturase1 expression and enzyme activity.
AB  - The trans-10,cis-12 isomer of conjugated linoleic acid (CLA) reduces body fat
      gain in animals and inhibits stearoyl-CoA desaturase (SCD) activity in 3T3-L1
      adipocytes. To test whether CLA's body fat reduction is mediated by SCD1, wild
      type and SCD1-null mice were fed diet supplemented with 0.2% trans-10,cis-12
      (t10c12) CLA for 4 weeks. The t10c12 CLA-supplemented diet significantly reduced
      body fat mass in both wild type and SCD1-null mice. Similarly, t10c12 CLA diet
      decreased blood triglyceride and free fatty acid levels regardless of SCD1
      genotypes. Mice fed t10c12 CLA exhibited increased mRNA expression of fatty acid
      synthase and uncoupling protein 2 in both genotypes. Taken together, the effects
      of t10c12 CLA on reduction of body fat gain, blood parameters, and mRNA
      expression in both SCD1-null mice and wild-type mice were similar, indicating
      that the anti-obesity effect of t10c12 CLA may be independent of the effects of
      this CLA isomer on SCD1 gene expression and enzyme activity.

PMID- 14975734
TI  - Ca2+-induced activation of ATPase activity of myosin Va is accompanied with a
      large conformational change.
AB  - We succeeded in expressing the recombinant full-length myosin Va (M5Full) and
      studied its regulation mechanism. The actin-activated ATPase activity of M5Full
      was significantly activated by Ca(2+), whereas the truncated myosin Va without C
      terminal globular domain is not regulated by Ca(2+) and constitutively active.
      Sedimentation analysis showed that the sedimentation coefficient of M5Full
      undergoes a Ca(2+)-induced conformational transition from 14S to 11S. Electron
      microscopy revealed that at low ionic strength, M5Full showed an extended
      conformation in high Ca(2+) while it formed a folded shape in the presence of
      EGTA, in which the tail domain was folded back towards the head-neck region.
      Furthermore, we found that the motor domain of myosin Va folds back to the neck
      domain in Ca(2+) while the head-neck domain is more extended in EGTA. It is
      thought that the association of the motor domain to the neck inhibits the binding
      of the tail to the neck thus destabilizing a folded conformation in Ca(2+). This
      conformational transition is closely correlated to the actin-activated ATPase
      activity. These results suggest that the tail and neck domain play a role in the
      Ca(2+) dependent regulation of myosin Va.

PMID- 14975735
TI  - Heme controls the expression of cell cycle regulators and cell growth in HeLa
      cells.
AB  - Heme plays a central role in oxygen utilization and in the generation of cellular
      energy. Here we examined the effect of heme and heme deficiency on cell cycle
      progression and the expression of key regulators in HeLa cells. We found that
      inhibition of heme synthesis causes cell cycle arrest and induces the expression
      of molecular markers associated with senescence and apoptosis, such as increased
      formation of PML nuclear bodies. Our data show that succinyl acetone-induced heme
      deficiency increases the protein levels of the tumor suppressor gene product p53
      and CDK inhibitor p21, and decreases the protein levels of Cdk4, Cdc2, and cyclin
      D2. Further, we found that heme deficiency diminishes the
      activation/phosphorylation of Raf, MEK1/2, and ERK1/2-components of the MAP
      kinase signaling pathway. Our results show that heme is a versatile molecule that
      can effectively control cell growth and survival by acting on multiple
      regulators.

PMID- 14975736
TI  - Differential regulation of phosphatidylinositol 3-kinase/Akt, mitogen-activated
      protein kinase, and AMP-activated protein kinase pathways during menadione
      induced oxidative stress in the kidney of young and old rats.
AB  - We investigated regulation of various signal transduction pathways during
      oxidative stresses in the kidney of young and aged rats. Menadione-induced
      regulation of molecules in PI 3-kinase, MAPK, and AMPK pathways was determined in
      the young (2 months) and old (24 months) groups. PI 3-kinase activity and Akt
      phosphorylation were significantly reduced in the old compared with the young.
      PTEN tumor suppressor was also lower in its expression and phosphorylation levels
      in the old. Response of the molecules in PI 3-kinase pathway to menadione was
      minimized. In contrast, over 5-fold induction of ERK1/2 phosphorylation by
      menadione was observed in both groups. On the other hand, basal activities as
      well as menadione-induced activities of JNK1 and AMPK were higher in the old than
      in the young. While p27(Kip1), p53, and p21(Waf1) were slightly increased by
      menadione in both groups, the basal induction level in the old was considerably
      higher. In conclusion, the results suggest that the age-related down-regulation
      of PI 3-kinase/Akt pathway and up-regulation of JNK1, AMPK, and p53 pathways may
      be responsible for the increased susceptibility to oxidative stress.

PMID- 14975737
TI  - Bcl-2 family gene modulation during spontaneous apoptosis of B-chronic
      lymphocytic leukemia cells.
AB  - Malignant cell accumulation in B-cell chronic lymphocytic leukemia (B-CLL) is
      primarily caused by defective apoptosis rather than increased proliferation. To
      further understand the role of Bcl-2 family members, known regulators of
      apoptosis, in the abnormal B-CLL survival, we have measured their mRNA levels in
      fresh B-CLL cells and in cultures undergoing spontaneous apoptosis. Using RNA
      protection assays we found constitutive expression of most bcl-2 members with
      high levels of bcl2, bcl-w, bad, bak, bax, and the bcl-2/bax ratio, compared to
      normal PBL. Spontaneous apoptosis of B-CLL cells by in vitro culture resulted in
      decreased bcl-2, bcl-w, bfl-1, mcl-1, bak, bax, and bcl-2/bax expression. The pro
      apoptotic member bik was only expressed in 5/19 cases and was not modulated
      during apoptosis, suggesting that bik is not involved in this process. Thus,
      several Bcl-2 family genes are regulated during B-CLL spontaneous apoptosis and
      their relative levels may contribute to in vivo progression of the disease.

PMID- 14975738
TI  - Identification and H2O2 sensitivity of the major constitutive MAPK phosphatase
      from rat brain.
AB  - The present study examined in subcellular fractions from rat brain the nature and
      sensitivity to hydrogen peroxide of constitutively expressed mitogen-activated
      protein kinase (MAPK) phosphatase activity. MAPK phosphatase activity was defined
      as the activity directed towards a dual-phosphorylated (pT/pY) peptide
      corresponding to the activation domain of the extracellular-regulated kinase
      (ERK) subtype of the MAPKs. The use of phosphatase inhibitors and biochemical
      analyses demonstrate that the MAPK phosphatase activity, which was highest in the
      microsomal membrane and soluble fractions, was attributable mainly, if not
      entirely, to protein phosphatase 2A (PP2A). Moreover, hydrogen peroxide (in the
      absence and presence of reduced glutathione) and glutathione disulfide inhibited
      the MAPK phosphatase activity by a dithiothreitol-reversible mechanism. These
      results provide direct support for mounting evidence that PP2A is a major
      regulator of MAPK phosphorylation in brain and suggest that inhibition of PP2A
      activity via reversible oxidation of a cysteine thiol(s) may underlie at least in
      part the activation of MAPKs occurring in response to hydrogen peroxide and
      oxidative stress.

PMID- 14975739
TI  - SMP30 deficiency in mice causes an accumulation of neutral lipids and
      phospholipids in the liver and shortens the life span.
AB  - Senescence marker protein-30 (SMP30) is an androgen-independent factor that
      decreases with aging. SMP30-deficient (SMP30Y/-) mice are viable and fertile but
      lower in body weight and shorter in life span than the wild-type. In the electron
      microscope, hepatocytes from SMP30Y/- but not the wild-type mice at 12 months of
      age clearly contained many lipid droplets, abnormally enlarged mitochondria with
      indistinct cristae, and enlarged lysosomes filled with electron-dense bodies. In
      liver specimens from SMP30Y/- mice, the marked number of lipid droplets visible
      around the central vein increased notably in size and amount as the animals aged.
      Biochemical analysis of neutral lipids, total hepatic triglyceride, and
      cholesterol from SMP30Y/- mice showed approximately 3.6- and 3.3-fold higher
      levels, respectively, than those from age-matched wild-type mice. Moreover,
      values for total hepatic phospholipids from SMP30Y/- mice were approximately 3.7
      fold higher than those for their wild-type counterparts. By thin-layer
      chromatography analysis, phosphatidylethanolamine, cardiolipin,
      phosphatidylcholine, phosphatidylserine, and sphingomyelin accumulations were
      detected separately in lipid extracts from SMP30Y/- mouse livers and provided
      results that strongly indicate the profound effect of an SMP30 deficiency on the
      metabolism of these neutral lipids and phospholipids. Conceivably, this
      abnormality of lipid metabolism is sufficient to curtail the life span of SMP30
      deficient mice.

PMID- 14975740
TI  - Newly expressed proteins of mouse embryonic fibroblasts irradiated to be
      inactive.
AB  - It has been found that post-radiation mouse embryonic fibroblasts can well
      maintain the pluripotency in human embryonic stem cells. However, the molecular
      mechanism remains unclear. In the present study, the new protein expression
      profile of post-radiation mouse embryonic fibroblasts was analyzed by immobilized
      pH gradient 2-dimensional polyacrylamide gel electrophoresis. Image analysis
      following silver staining revealed (969+/-57) vs. (1085+/-107) spots from post
      radiation mouse embryonic fibroblasts and pre-radiation ones, respectively. Some
      newly expressed proteins, which were only abundantly present after irradiation,
      were subjected to peptide mass fingerprint analysis and identified using MALDI
      TOF-MS, SWISS-PROT database, and RT-PCR. Several of those proteins were
      preliminarily identified to participate in cytokine secretion, cell signal
      transduction, transcriptional regulation, and apoptosis, etc., which suggested
      that inactive post-radiation mouse embryonic fibroblasts expressed some new
      proteins that may underlie the molecular mechanisms to maintain the pluripotency
      in human embryonic stem cells.

PMID- 14975741
TI  - alpha-Bisabolol, a nontoxic natural compound, strongly induces apoptosis in
      glioma cells.
AB  - In this study, alpha-bisabolol, a sesquiterpene alcohol present in natural
      essential oil, was found to have a strong time- and dose-dependent cytotoxic
      effect on human and rat glioma cells. After 24 h of treatment with 2.5-3.5 microM
      alpha-bisabolol, the viability of these cells was reduced by 50% with respect to
      untreated cells. Furthermore, the viability of normal rat glial cells was not
      affected by treatment with alpha-bisabolol at the same concentrations as above.
      Glioma cells treated with high concentration of alpha-bisabolol (10 microM)
      resulted in a 100% cell death. Judging from hypo-G1 accumulation, poly(ADP
      ribose) polymerase cleavage, and DNA ladder formation, the cytotoxicity triggered
      by alpha-bisabolol resulted from apoptosis induction. Moreover, the dissipation
      of mitochondrial-inner transmembrane potential and the release of cytochrome c
      from mitochondria indicated that, in these glioma cells, apoptosis occurred
      through an intrinsic pathway. As pointed out by the experimental results, alpha
      bisabolol may be considered a novel compound able to inhibit glioma cell growth
      and survival.

PMID- 14975742
TI  - Effect on ribonucleotide reductase of novel lipophilic iron chelators: the
      desferri-exochelins.
AB  - Desferri-exochelins are siderophores secreted by Mycobacterium tuberculosis that
      are both lipid- and water-soluble and have a high binding affinity for iron.
      Desferri-exochelin 772SM inhibits DNA replication and ribonucleotide reductase
      activity at 10-fold less concentration than the lipid-insoluble iron chelator
      deferoxamine, which is currently in clinical use. Neither chelator can extract
      iron directly from ribonucleotide reductase. However, because of its lipid
      solubility and high binding affinity, desferri-exochelin is able to enter cells
      rapidly and access intracellular iron, while deferoxamine has limited capacity to
      cross the cell membrane.

PMID- 14975743
TI  - A hypothermic-temperature-sensitive gene silencing by the mammalian RNAi.
AB  - RNA interference (RNAi) has been attracting a great deal of attention. This
      pathway is highly conserved among most eukaryotes and believed to be important
      for antiviral reactions and epigenetic gene regulation. Because a temperature
      sensitive RNAi was reported in both plant and insect systems, suggesting its
      evolutional conservation, we analyzed the effect of different temperatures on
      mammalian RNAi, targeting the ectopic gene expression, and detected suppression
      at hypothermic temperatures. This phenomenon could be critical and useful to
      control ectopic and internal gene expressions by RNAi.

PMID- 14975744
TI  - A novel function of N-cadherin and Connexin43: marked enhancement of alkaline
      phosphatase activity in rat calvarial osteoblast exposed to sulfated hyaluronan.
AB  - In this study, we examined the interaction of the osteoblast which forms bone and
      sulfated hyaluronan (SHya). For the purpose of the creation of a new functional
      polysaccharide, we introduced a sulfate group in hyaluronan (Hya) of high
      molecular weight, and SHya of high molecular weight could be obtained for the
      first time. When rat calvarial osteoblast (rOB) cells were cultured with a high
      concentration of SHya, they formed aggregated spheroids after 4h and the
      spheroids grew to about 200microm after 24h. We examined the expression of cell
      adhesion molecules in order to clarify the mechanism of aggregate formation. The
      N-cadherin (N-cad) and Connexin43 (Cx43) expression level of rOB cells cultured
      with SHya remarkably increased after 2h. A difference in the expression of
      Integrin beta1 (Intbeta1) could not be observed between the SHya addition and
      control group. The alkaline phosphatase (ALPase) activity of rOB cells cultured
      with SHya after 8h was significantly enhanced in comparison with control.
      Therefore, the sulfate group of SHya seems to enhance expression of cell adhesion
      protein such as N-cad and Cx43, resulting in aggregate formation and further
      remarkable induction of the ALPase activity of rOB cells.

PMID- 14975745
TI  - Improvement of catalytic antibody activity by protease processing.
AB  - An immunoglobulin L chain (HIR) was treated with lysyl-endopeptidase. Gel
      filtration chromatography of the digestion mix identified a peak displaying a
      significantly higher specific catalytic activity than that of the original
      sample. The protein in the peak was 11 kDa in size and constituted the VL
      fragment of HIR. The Km and Kcat values of Chromozym TRY hydrolysis for HIR were
      1.5 x 10(-4) M and 6.2 min(-1), and for the VL fragment 7.3 x 10(-4) M and 4.8 x
      10(2) min(-1), respectively. Three out of the five BJPs studied in this paper
      displayed elevated catalytic activity after processing with lysyl-endopeptidase.
      Similar results were also obtained for the complete antibody.

PMID- 14975746
TI  - ARL1 participates with ATC1/LIC4 to regulate responses of yeast cells to ions.
AB  - ATC1/LIC4, previously identified as a suppressor of the Li(+)-sensitive phenotype
      of calcineurin mutants, was also identified as a suppressor of the hygromycin B
      sensitive phenotype of strains lacking the G protein gene, ARL1. Although loss of
      ARL1 confers several phenotypes, including sensitivity to hygromycin B and Li(+),
      reduced influx of K(+), and increased secretion of carboxypeptidase Y (CPY), loss
      of ATC1 was without effect by these and other measures. However, loss of ATC1 in
      an arl1 background exacerbated ion sensitivities, although not the CPY phenotype.
      Moreover, overexpression of ATC1 in an arl1 background partially suppressed ion
      sensitivities, but not the CPY phenotype. Additionally, expression of ENA1, the
      Na(+)/Li(+) efflux ATPase, and activated calcineurin, but not normal calcineurin,
      suppressed the Li(+)-sensitive phenotype of the arl1 atc1 double mutant. These
      results show ARL1 and ATC1 interact to control intracellular ion levels, but ATC1
      has little influence on other functions of ARL1.

PMID- 14975747
TI  - Rapid induction of apoptosis in prostate cancer cells by selenium: reversal by
      metabolites of arachidonate 5-lipoxygenase.
AB  - Recent clinical trials have documented that selenium significantly reduces the
      incidence of clinical prostate cancer. However, nothing is clearly known about
      the underlying molecular mechanisms by which selenium exerts its anti-cancer
      effect. This report provides evidence that selenium at micro-molar concentrations
      induces rapid apoptotic death in human prostate cancer cells, but not in normal
      prostate epithelial cells. Apoptosis involves activation of caspase 3 which plays
      a critical role in the cell death process. Interestingly, the apoptosis-inducing
      effect of selenium in prostate cancer cells is substantially alleviated by the 5
      lipoxygenase metabolites, 5(S)-HETE and its dehydrogenated derivative 5-oxoETE,
      but not by metabolites of 12-lipoxygenase (12(S)-HETE) or 15-lipoxygenase (15(S)
      HETE). Apoptosis is also prevented by their precursor, arachidonic acid, an omega
      6, polyunsaturated fatty acid, presumably by metabolic conversion through the 5
      lipoxygenase pathway. These results indicate that selenium's anticancer effect
      may involve induction of apoptosis specifically in prostate cancer cells sparing
      normal prostate epithelial cells, and that 5-lipoxygenase may be a molecular
      target of selenium's anticancer action. The present report warrants that care
      should be taken about high intake of dietary fat containing arachidonic acid or
      its precursor fatty acids when selenium is used for the management of prostate
      cancer, and suggests that a combination of selenium and 5-lipoxygenase inhibitors
      may be a more effective regimen for prostate cancer control.

PMID- 14975748
TI  - Statins inhibit osteoblast migration by inhibiting Rac-Akt signaling.
AB  - Cell migration is a key event in repair and remodeling of skeletal tissues, but
      the mechanism of osteoblast migration has not been resolved. Statins, which are
      inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase, increase bone. However,
      the effect of statins on osteoblast migration remains to be clarified. We
      investigated the effect of fluvastatin and mevastatin on platelet-derived growth
      factor (PDGF)-induced migration of osteoblastic MC3T3-E1 cells. PDGF promoted
      osteoblast migration, while the statins inhibited PDGF-induced migration, and
      mevalonate and geranylgeranylpyrophosphate but not farnesylpyrophosphate
      abolished the effect of statins. Dominant-negative Rac severely inhibited PDGF
      induced osteoblast migration and reduced Akt phosphorylation. Further,
      fluvastatin reduced Akt phosphorylation and dominant-negative Akt inhibited PDGF
      induced osteoblast migration. These results demonstrate that statins inhibit PDGF
      induced osteoblast migration and Rac-Akt signaling plays an important role in the
      osteoblast migration, and suggest that statins restrain Rac function by
      inhibiting geranylgeranylation of Rac, which leads to the reduction in Akt
      activation and osteoblast migration.

PMID- 14975750
TI  - Cloning and biochemical characterization of a novel mouse ADP-dependent
      glucokinase.
AB  - Glycolysis, the catabolism of glucose to pyruvate, is an iconic central metabolic
      pathway and often used as a paradigm for explaining the general principles of the
      regulation/control of cellular metabolism. The ubiquitous mammalian ATP-dependent
      hexokinases I-III and hexokinase IV, also termed glucokinase, initiate the
      process by phosphorylating glucose to glucose-6-phosphate. Despite glycolysis
      having been studied extensively for over 70 years and the last new mammalian ATP
      dependent hexokinase isotype having been described in the 1960s, we report here
      the biochemical characterization of a recombinant ADP-dependent glucokinase
      cloned from a full-length Mus musculus cDNA, identified by sequence analysis. The
      recombinant enzyme is quite specific for glucose, is monomeric, has an apparent
      Km for glucose and ADP of 96 and 280 microM, respectively, and is inhibited by
      both high concentrations of glucose and AMP. The metabolic role of this enzyme in
      cells would be dependent on the relative level of its activity to those of the
      ATP-dependent hexokinases. The greatest advantage of an ADP-GK would clearly be
      during ischemia/hypoxia, clinically relevant conditions in multiple major disease
      states, by decreasing the priming cost for the phosphorylation of glucose, saving
      ATP.

PMID- 14975749
TI  - Immortalization of human osteoblasts by transferring human telomerase reverse
      transcriptase gene.
AB  - In the current study, in order to establish an immortalized osteoblast cell line,
      human mesenchymal stem cells (hMSCs) had been inducted into osteoblasts
      directionally by an osteo-inductive conditioned medium, then the osteoblasts were
      steadily transduced by a retroviral vector containing human telomerase reverse
      transcriptase (hTERT) gene. The expression of hTERT, the telomerase activity, the
      telomere lengths, the tumorigenesis and the osteogenesis characteristics of
      transduced cells at different population doublings (PDs) and the primary normal
      human osteoblast (hOB) were identified. The results demonstrated that hTERT gene
      had been transferred into human osteoblasts successfully; the transduced cell
      line-clone5 expressed telomerase activity and divided vigorously and now have
      undergone more than 120 PDs; The telomere length of clone5 elongated and was
      stable; Different eras of clone5 (PD 40 and PD 88) both expressed bone-specific
      markers, such as alkaline phosphatase (ALP), collagen type I, and osteopontin.
      And the quantitative assay of ALP activity showed that there were no significant
      differences among untransduced cells, PD 40 and PD 88 clone5 cells. Furthermore,
      the immortalized cell line was benign in nude mice tumor formation and soft agar
      colony formation assay.

PMID- 14975751
TI  - Conformational transition state is responsible for assembly of microtubule
      binding domain of tau protein.
AB  - In the brains of Alzheimer's disease patients, the tau protein dissociates from
      the axonal microtubule and abnormally aggregates to form a paired helical
      filament (PHF). One of the priorities in Alzheimer research is to clarify the
      mechanism of PHF formation. Although several reports on the regulation of tau
      assembly have been published, it is not yet clear whether in vivo PHFs are
      composed of beta-structures or alpha-helices. Since the four-repeat microtubule
      binding domain (4RMBD) of the tau protein has been considered to play an
      essential role in PHF formation, its heparin-induced assembly propensity was
      investigated by the thioflavin fluorescence method to clarify what conformation
      is most preferred for the assembly. We analyzed the assembly propensity of 4RMBD
      in Tris-HCl buffer with different trifluoroethanol (TFE) contents, because TFE
      reversibly induces the transition of the random structure to the alpha-helical
      structure in an aqueous solution. Consequently, it was observed that the 4RMBD
      assembly is most significantly favored to proceed in the 10-30% TFE solution, the
      concentration of which corresponds to the activated transition state of 4RMBD
      from a random structure to an alpha-helical structure, as determined from the
      circular dichroism (CD) spectral changes. Since such an assembly does not occur
      in a buffer containing TFE of < 10% or > 40%, the intermediate conformation
      between the random and alpha-helical structures could be most responsible for the
      PHF formation of 4RMBD. This is the first report to clarify that the non-native
      alpha-helical intermediate in transition from random coil is directly associated
      with filament formation at the start of PHF formation.

PMID- 14975752
TI  - Basis for fusion inhibition by peptides: analysis of the heptad repeat regions of
      the fusion proteins from Nipah and Hendra viruses, newly emergent zoonotic
      paramyxoviruses.
AB  - Nipah virus (NiV) and Hendra virus (HeV) are novel zoonotic members of the
      Paramyxoviridae family and are the prototypes for a newly designated genus, Genus
      Henipavirus. Recent studies have shown that paramyxovirus might adopt a similar
      mechanism of virus fusion-entry. Under this mechanism, the two highly conserved
      heptad repeat (HR) regions, HR1 and HR2, in the fusion (F) protein, seem to show
      characteristic structure in the fusion core: the formation of a 6-helix coiled
      coil bundle. The three HR1s form the alpha-helix coiled-coil surrounded by three
      HR2s. In this study, the two HR regions of NiV or HeV were expressed in an
      Escherichia coli system as a single chain and the results do show that HR1 and
      HR2 interact with each other in both NiV and HeV and form typical 6-helix coiled
      coil bundles. This provides the molecular basis of HR2 inhibition to NiV and HeV
      fusion as observed in an earlier report.

PMID- 14975753
TI  - Sorting of Von Willebrand factor to lysosome-related granules of haematopoietic
      cells.
AB  - The aim of this work was to investigate sorting mechanisms of von Willebrand
      factor (VWF) when expressed in haematopoietic cells. The processing and sorting
      of both the wild-type VWF and a multimerization defective propeptide-mutant
      (VWF(m)) were investigated after expression in the 32D cell line. Normal
      proteolytic processing was observed for both proteins, however the processing of
      VWF(m) was much slower and a large portion was unprocessed. Results from
      subcellular fractionation and immunoelectron microscopy confirmed that a part of
      VWF, but not VWF(m), was targeted to lysosome-related granules. Partial
      constitutive secretion was also observed for all forms of VWF and VWF(m).
      Inhibition of acidification by chloroquine blocked VWF processing but allowed
      unprocessed pro-VWF targeting to dense organelles. In conclusion, our
      observations are consistent with VWF multimerization being of importance in
      cellular retention and targeting to lysosome-related organelles in haematopoietic
      cells, suggesting a role of protein aggregation for sorting in these cells.

PMID- 14975754
TI  - Characterization and tissue distribution of a novel human cytochrome P450-CYP2U1.
AB  - A novel human cytochrome P450 cDNA designated CYP2U1 was identified using
      homology searches, and the corresponding gene is located on chromosome 4. The
      deduced 544 amino acid sequence displays up to 39% identity to other CYP2 family
      members, with closest resemblance to CYP2R1 and is highly conserved between
      species. CYP2U1 shows some structural differences compared to other CYP2 family
      members. The gene has only five exons and the enzyme harbors two insertions in
      the N-terminal region. Northern blot analysis revealed high mRNA expression in
      human thymus, with weaker expression in heart and brain, whereas in the rat
      similar mRNA levels were detected in thymus and brain. Western blot analysis
      revealed much higher CYP2U1 protein expression in rat brain than in thymus,
      particularly in limbic structures and in cortex. The physiological and
      toxicological role of this novel P450 is still unknown, but the selective tissue
      distribution suggests an important endogenous function.

PMID- 14975755
TI  - Expression of seven main Rho family members in gastric carcinoma.
AB  - Rho GTPases were previously shown to have an important role in cancer development
      and progression, including cell transformation, proliferation, invasion,
      metastasis, and angiogenesis. However, there is still little information
      available on the clinical significance of Rho GTPases expression in human cancer
      specimens. In the present study, we systemically investigated the mRNA expression
      levels of seven main members RhoA, RhoB, RhoC, Rac1, Rac2, Rac3, and Cdc42 of Rho
      family using semi-quantitative reverse transcription-PCR in 53 patients with
      gastric carcinoma and 7 gastric cancer cell lines. The total and activities of
      RhoA, Rac1 and Cdc42 in 5 gastric cancer cell lines were also examined. The mean
      mRNA expression levels of RhoA and Rac1 in gastric cancer tissue specimens were
      significantly higher than those in the adjacent non-tumorous tissue specimens (p
      < 0.01). The higher expression of RhoA was significantly correlated with higher
      TNM stage (p < 0.05) as well as with pooly differentiated histological type (p <
      0.05) of gastric carcinoma. The increased expression of Rac1 was related to
      higher TNM stages of gastric carcinoma (p < 0.05). The expression levels of mRNA,
      total protein and activities of RhoA and Rac1 in 7 gastric cancer cell lines were
      all higher than that in gastric mucosal epithelial cell line GES-1. These
      findings indicate that RhoA and Rac1 may play important roles in the
      carcinogenesis and progression of gastric carcinoma.

PMID- 14975756
TI  - Cross-talk between endocrine-disrupting chemicals and cytokine signaling through
      estrogen receptors.
AB  - STAT3 mainly acts as a signal transducer of IL-6 family cytokines and
      transcriptionally activates specific target genes. STAT3 has also been
      demonstrated to mediate cellular transformation and is found in numerous cancers.
      Endocrine-disrupting chemicals (EDCs) are a diverse group of chemicals that bind
      to estrogen receptors (ERs), mimic estrogenic actions, and may have adverse
      effects on human health. In our previous study, we demonstrated that estrogens
      suppressed the STAT3-mediated transcription activity through ERs. In this study,
      we examined the effects of EDCs on STAT3-mediated signaling through ERs.
      Surprisingly, some of EDCs enhanced STAT3-mediated transcription activity through
      ERs. This finding strongly suggests that EDCs may play an important role in the
      endocrine functions by mimicking cytokine activity by stimulating STAT3 actions
      through ERs.

PMID- 14975757
TI  - Acarbose attenuates experimental non-alcoholic steatohepatitis.
AB  - The alpha-glucosidase inhibitor acarbose is beneficial in the prevention of type
      2 diabetes. To determine whether it attenuates the commonly associated non
      alcoholic steatohepatitis (NASH), we used an experimental NASH model. Rats were
      fed ad libitum a nutritionally adequate high fat diet (71% of calories as fat)
      with or without acarbose (200 mg/1000 calories) for 3 weeks. All rats given the
      high fat diet only developed typical NASH whereas acarbose attenuated several of
      the characteristic hepatic alterations of NASH: there was less steatosis and
      inflammation, with a significant reduction in the mRNA of the hepatic
      inflammatory cytokine TNF-alpha and of its protein. There was also a decrease in
      the CYP2E1 mRNA and in collagen, with similar trends for CYP2E1 protein and
      procollagen mRNA. Because acarbose attenuates many of the hepatic alterations
      associated with experimental NASH, it is now indicated to determine whether it
      exerts similar beneficial effects in patients afflicted by this disease.

PMID- 14975758
TI  - Lipoxygenase-catalyzed polymerization of phenolic lipids suggests a new mechanism
      for allergic contact dermatitis induced by urushiol and its analogs.
AB  - Lipoxygenase was found to catalyze the oxidative polymerization of phenolic
      lipids containing a (Z,Z)-pentadiene in the side chain, the model compounds of
      urushiol and its analog, yielding methanol-soluble and insoluble polymers. The
      structural analysis of the resulted polymers suggested that the polymerization
      occurred at both the phenol and the unsaturated side chain. The key step of the
      polymerization was the generation of the hydroperoxide at the unsaturated side
      chain by lipoxygenase. The decomposition of hydroperoxide and concomitant
      dehydrogenation of phenol ring catalyzed by lipoxygenase might produce radicals
      that could be coupled to form cross-linked polymers. This lipoxygenase-mediated
      reaction implies a new mechanism for contact allergy of urushiol and its analogs.

PMID- 14975759
TI  - Kinetics of parasite cysteine proteinase inactivation by NO-donors.
AB  - NO-donors block Plasmodium, Trypanosoma, and Leishmania life cycle inactivating
      parasite cysteine proteinases. In this study, the inactivation of falcipain,
      cruzipain, and Leishmania infantum cysteine proteinase by S-nitroso-5
      dimethylaminonaphthalene-1-sulphonyl (dansyl-SNO), S-nitrosoglutathione (GSNO),
      (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (NOR-3), and S
      nitrosoacetylpenicillamine (SNAP) is reported. With NO-donors in excess over the
      parasite cysteine proteinase, the time course of enzyme inactivation corresponds
      to a pseudo-first-order reaction for more than 90% of its course. The
      concentration dependence of the pseudo-first-order rate constant is second-order
      at low NO-donor concentrations but tends to first-order at high NO-donor
      concentrations. This behavior may be explained by a relatively fast pre
      equilibrium followed by a limiting pseudo-first-order process. Kinetic parameters
      of cruzipain inactivation by GSNO were affected by the acidic pK shift of one
      ionizing group (from pKunl = 5.7 to pKlig = 4.8) upon GSNO-induced enzyme
      inactivation. Falcipain, cruzipain, and L. infantum cysteine proteinase
      inactivation by dansyl-SNO, GSNO, NOR-3, and SNAP is prevented and reversed by
      dithionite and l-ascorbic acid. However, the incubation of L. infantum cysteine
      proteinase with dansyl-SNO does not result in the appearance of fluorescence of
      the enzyme. More than 90% of the S-transnitrosylation product GSH existed in the
      inactivation reaction, suggesting that S-transnitrosylation is the favorite
      process for parasite cysteine proteinase inactivation. Furthermore, the
      fluorogenic substrate N-alpha-benzyloxycarbonyl-l-phenylalanyl-l-arginine-(7
      amino-4-methylcoumarin) protects L. infantum cysteine proteinase from
      inactivation by SNAP. These results indicate that parasite cysteine proteinase
      inactivation by NO-donors occurs via NO-mediated S-nitrosylation of the Cys25
      catalytic residue.

PMID- 14975760
TI  - Mapping of the MRPm5 epitope to the cytosolic region between transmembrane
      helices 13 and 14 in the drug and organic anion transporter, MRP1 (ABCC1).
AB  - Multidrug resistance in human tumour cells is often associated with increased
      expression of the 190kDa multidrug resistance protein, MRP1, that belongs to the
      ATP-binding cassette superfamily of transport proteins. MRP1 is also an efficient
      transporter of many organic anions. In the present study, we have mapped the
      epitope of the MRP1-specific murine monoclonal antibody (MAb) MRPm5 to the
      decapeptide (1063)FFERTPSGNL(1072) located in the cytoplasmic loop (CL6) linking
      transmembrane helices 13 and 14 in the third membrane spanning domain of the
      protein. Several amino acids in the cytoplasmic loops of MRP1 have been reported
      to be important for its transport function; nevertheless, MAb MRPm5 does not
      inhibit vesicular uptake of the high affinity substrate leukotriene C(4). None of
      the other MRP1-reactive MAbs described to date map to CL6 of MRP1 which in turn
      enhances the utility of MAb MRPm5 for both clinical and experimental
      investigations of this transporter.

PMID- 14975761
TI  - Structure determination of fibrillarin from the hyperthermophilic archaeon
      Pyrococcus furiosus.
AB  - The methyltransferase fibrillarin is the catalytic component of ribonucleoprotein
      complexes that direct site-specific methylation of precursor ribosomal RNA and
      are critical for ribosome biogenesis in eukaryotes and archaea. Here we report
      the crystal structure of a fibrillarin ortholog from the hyperthermophilic
      archaeon Pyrococcus furiosus at 1.97A resolution. Comparisons of the X-ray
      structures of fibrillarin orthologs from Methanococcus jannashii and
      Archaeoglobus fulgidus reveal nearly identical backbone configurations for the
      catalytic C-terminal domain with the exception of a unique loop conformation at
      the S-adenosyl-l-methionine (AdoMet) binding pocket in P. furiosus. In contrast,
      the N-terminal domains are divergent which may explain why some forms of
      fibrillarin apparently homodimerize (M. jannashii) while others are monomeric (P.
      furiosus and A. fulgidus). Three positively charged amino acids surround the
      AdoMet-binding site and sequence analysis indicates that this is a conserved
      feature of both eukaryotic and archaeal fibrillarins. We discuss the possibility
      that these basic residues of fibrillarin are important for RNA-guided rRNA
      methylation.

PMID- 14975762
TI  - Expression of p300 protects cardiac myocytes from apoptosis in vivo.
AB  - Doxorubicin is an anti-tumor agent that represses cardiac-specific gene
      expression and induces myocardial cell apoptosis. Doxorubicin depletes cardiac
      p300, a transcriptional coactivator that is required for the maintenance of the
      differentiated phenotype of cardiac myocytes. However, the role of p300 in
      protection against doxorubicin-induced apoptosis is unknown. Transgenic mice
      overexpressing p300 in the heart and wild-type mice were subjected to doxorubicin
      treatment. Compared with wild-type mice, transgenic mice exhibited higher
      survival rate as well as more preserved left ventricular function and cardiac
      expression of alpha-sarcomeric actin. Doxorubicin induced myocardial cell
      apoptosis in wild-type mice but not in transgenic mice. Expression of p300
      increased the cardiac level of bcl-2 and mdm-2, but not that of p53 or other
      members of the bcl-2 family. These findings demonstrate that overexpression of
      p300 protects cardiac myocytes from doxorubicin-induced apoptosis and reduces the
      extent of acute heart failure in adult mice in vivo.

PMID- 14975763
TI  - beta-Helix is a likely core structure of yeast prion Sup35 amyloid fibers.
AB  - We have studied the core structure of amyloid fibers of yeast prion protein
      Sup35. We developed procedures to prepare straight fibers of relatively uniform
      diameters from three kinds of fragments; N (1-123), NMp (1-189), and NM (1-253).
      X-ray fiber diffraction patterns from dried oriented fibers gave common
      reflections in all three cases; a sharp meridional reflection at 4.7A, and a
      diffuse equatorial peak at around 9A, apparently supporting the typical "cross
      beta" structure with stacked beta-sheets proposed for many different amyloid
      fibers. However, X-ray fiber diffraction from hydrated fibers showed the
      meridional reflection at 4.7A but no equatorial reflections at 9A in all three
      cases, indicating that the stack of beta-sheets in dried fibers is an artifact
      produced by drying process. Thus, the core structure of these amyloid fibers made
      of the N domain is likely to be beta-helix nanotube as proposed by Perutz et al.

PMID- 14975764
TI  - Effects of tempol on renal angiotensinogen production in Dahl salt-sensitive
      rats.
AB  - We have recently reported that Dahl salt-sensitive rats (DS) on high salt diet
      (HS) have an inappropriate augmentation of intrarenal angiotensinogen. Recent
      studies also reported that the augmented superoxide anion formation plays
      important roles in this animal model of hypertension. This study was performed to
      address the hypothesis that an inappropriate augmentation of intrarenal
      angiotensinogen by HS is caused by the augmented reactive oxygen species. Male DS
      (200-220 g) were maintained on low salt diet LS (N = 7) or HS (N = 27) for 4
      weeks. The HS group was subdivided into three subgroups to receive null (N = 12),
      superoxide dismutase mimetic, tempol (3 mmol/l, N = 8), or vasodilator,
      hydralazine (0.5 mmol/l, N = 7) in drinking water during the period. Systolic BP
      was significantly increased in the DS+HS group compared to the DS+LS group (184+/
      7 mmHg vs. 107+/-5 at 4-week). Tempol or hydralazine treatment equivalently
      attenuated the hypertension (128+/-3 and 127+/-5 at 4-week, respectively).
      Urinary excretion of thiobarbituric acid reactive substances at 4-week was
      significantly increased in the DS+HS group compared to the DS+LS group (0.66+/
      0.05 micromol/day vs. 0.14+/-0.01). Tempol treatment prevented this effect
      (0.24+/-0.04) but hydralazine treatment only partially prevented the effect
      (0.40+/-0.03). Kidney angiotensinogen levels, measured by Western blot analysis,
      were significantly increased in the DS+HS group compared to the DS+LS group (32+/
      5 densitometric units vs. 21+/-1). Tempol (14+/-3) but not hydralazine (32+/-5)
      treatment prevented the intrarenal angiotensinogen augmentation. The evidence
      suggests that the enhanced intrarenal angiotensinogen in DS challenged with HS is
      associated with the augmented reactive oxygen species.

PMID- 14975765
TI  - Characterization of phytochelatin synthase-like protein encoded by alr0975 from a
      prokaryote, Nostoc sp. PCC 7120.
AB  - Phytochelatins (PCs) are well known as the heavy metal-detoxifying peptides in
      higher plants, eukaryotic algae, fungi, and nematode. In contrast, neither PCs
      nor PC synthase genes have ever been identified in any prokaryotes. The genome
      sequences for the cyanobacterium Nostoc sp. PCC 7120 were recently completed and
      allowed us to identify a gene encoding a PC synthase-like protein, termed
      alr0975. The predicted product of alr0975 contains the conserved N-terminal
      domain but not the variable C-terminal domain found in eukaryotic PC synthases.
      The recombinant alr0975 protein strongly catalyzed the first step of PC
      synthesis, in which glutathione (GSH) is converted to gamma-glutamylcysteine
      (gamma-EC), although the protein only weakly catalyzed the second step of PC
      synthesis, namely the transfer of gamma-EC moiety to an acceptor GSH molecule to
      form PC(2). These results suggest alr0975 protein may be a more primitive form of
      the PC synthases found in eukaryotes.

PMID- 14975766
TI  - Characterization of the interaction of P1,P4-diadenosine 5'-tetraphosphate with
      luciferase.
AB  - Adenylated dinucleotides (Ap(n)A) are regulatory molecules that control various
      cellular processes. A very likely intracellular target for Ap(4)A are enzymes
      that require ATP as either substrate or modulator. We report the results of new
      biochemical studies aimed at characterizing the Ap(4)A interaction with firefly
      luciferase, by using the luminometric and thin layer chromatography techniques.
      The data presented herein demonstrate that Ap(4)A is a noncompetitive inhibitor
      for the ATP-induced luminescence. These results together with our previous
      findings that Ap(4)A is a luciferase substrate [Nucleosides Nucleotides Nucleic
      Acids 23 (2004) in press.] support the notion that, similar to its interaction
      with P(2) receptors, Ap(4)A also has a dual interaction with luciferase. Other
      Ap(n)As (n = 2, 5, and 6) also inhibited the ATP-luciferase interaction. Since
      Ap(n)As may have similar interactions with other intracellular ATP-requiring
      enzymes, the study presented herein validates ulterior investigations of the
      Ap(n)A interaction with such enzymes, and opens the way to a better understanding
      of their intracellular roles.

PMID- 14975767
TI  - Formation and dynamic alterations of horizontal microdomains in sperm membranes
      during progesterone-induced acrosome reaction.
AB  - Capacitated mammalian spermatozoa undergo a fusion response of their head plasma
      membrane and the outer acrosomal membrane leading to vesiculation classically
      known as acrosome reaction. Acrosome reaction occurs in response to various
      acrosome reaction inducers including zona pellucida proteins, calcium ionophore,
      dibutyryl cAMP, progesterone, etc. All the acrosome reaction inducers cause a
      transient of calcium influx into the sperm through voltage-dependent cation
      channels. Efflux of chloride, stimulation of activity of phospholipases, and
      phosphorylation of proteins are other known changes introduced by acrosome
      reaction inducers. Macromolecular organization and dynamics of sperm membranes
      during the progression of this vesiculation are largely unexplored. In this
      study, we report that progesterone induced the formation of horizontal
      microdomains within the exofacial surfaces of sperm membranes, which showed
      progressive and independent alterations in molecular dynamics. In the light of
      this observation, we propose that sperm membrane rafts may contain both
      horizontal and vertical microdomains.

PMID- 14975768
TI  - Bcl-2 and Bcl-xL are important for the induction of paclitaxel resistance in
      human hepatocellular carcinoma cells.
AB  - In this study we have investigated the mechanism underlying resistance to the
      chemotherapeutic drug paclitaxel in tumors of hepatocellular carcinoma (HCC)
      patients. Treatment with paclitaxel led to potent inhibition of growth of Hep3B
      hepatoma cells, but did not affect the growth properties of SNU-368 and SNU-398
      cell lines that were established from primary HCC tumors. The growth inhibitory
      effect induced by paclitaxel correlated with levels of intracellular p21 and
      resulted in cell cycle arrest at the G2/M phase. However, paclitaxel treatment
      did not alter intracellular p53 levels. Instead, SNU-398 cells express high
      levels of the anti-apoptotic Bcl-2 and Bcl-x(L) proteins and the level of Bcl
      x(L) could be further induced upon paclitaxel treatment. In contrast, Hep3B cells
      express pro-apoptotic members of the Bcl family and fail to induce Bcl-x(L) upon
      paclitaxel treatment. Therefore, these results strongly suggest that Bcl-2 and
      Bcl-x(L) play an important role in mediating resistance to paclitaxel.

PMID- 14975769
TI  - Attention to phobic stimuli during exposure: the effect of distraction on anxiety
      reduction, self-efficacy and perceived control.
AB  - To replicate and extend the finding that distraction facilitates between session
      anxiety reduction (), 27 spider phobics underwent three 10-min sessions of in
      vivo exposure followed by one 10-min exposure session at a 4-week follow-up,
      while having either stimulus-relevant focused conversation or stimulus-irrelevant
      distracting conversation with the experimenter. Physiological arousal and
      subjective anxiety were measured during exposure, and self-efficacy, perceived
      control and performance on a behavioural task were measured at pre-treatment,
      post session-3, and follow-up. Monitoring and blunting coping styles were also
      measured at pre-treatment to assess their impact on treatment outcome. Despite
      equal physiological activation between the groups, those who underwent distracted
      exposure showed greater reductions in subjective fear within and between
      sessions, and showed greater increases in self-efficacy ratings, internal
      perceived control and performance on a behavioural task. Coping style did not
      interact with the effect of distraction or focusing during exposure, however
      blunters had less subjective anxiety reduction overall, particularly when they
      underwent focused exposure. Results are discussed in terms of the emotional
      processing model and self-efficacy theory.

PMID- 14975770
TI  - A survey of psychologists' attitudes towards and utilization of exposure therapy
      for PTSD.
AB  - Although research supports the efficacy of exposure therapy for PTSD, some
      evidence suggests that exposure is under-utilized in general clinical practice.
      The purpose of this study was to assess licensed psychologists' use of imaginal
      exposure for PTSD and to investigate perceived barriers to its implementation. A
      total of 852 psychologists from three states were randomly selected and surveyed.
      An additional 50 members of a trauma special interest group of a national
      behavior therapy organization were also surveyed. The main survey results
      indicate that a large majority of licensed doctoral level psychologists do not
      report use of exposure therapy to treat patients with PTSD. Although
      approximately half of the main study sample reported that they were at least
      somewhat familiar with exposure for PTSD, only a small minority used it to treat
      PTSD in their clinical practice. Even among psychologists with strong interest
      and training in behavioral treatment for PTSD, exposure therapy is not completely
      accepted or widely used. Clinicians also appear to perceive a significant number
      of barriers to implementing exposure.

PMID- 14975771
TI  - Avoidance and depression: the construction of the cognitive-behavioral avoidance
      scale.
AB  - Previous research has demonstrated a relationship between avoidance and
      depression, although the nature of this relationship has been confused by
      inconsistent definitions of avoidance. Following a review of the construct of
      avoidance and an examination of past research, a new multidimensional measure of
      avoidance was developed and validated using an undergraduate student sample (245
      females and 146 males). Four reliable factors reflecting combinations of
      cognitive/behavioral and social/nonsocial dimensions of avoidance were obtained
      from the factor analysis of the new scale, entitled the "Cognitive-Behavioral
      Avoidance Scale" (CBAS). The scale showed the predicted relationships with
      convergent and divergent measures used for construct validation. As predicted,
      subscales of the CBAS, as well as the overall scale score, were significantly
      related to the depression and anxiety criterion measures. The findings from this
      study suggest that avoidance may be an important construct in the psychosocial
      conceptualization of depression. In addition, this integrated measure of
      avoidance has potential utility for depression researchers. Suggestions for
      further scale development and research are provided.

PMID- 14975772
TI  - The relationship between acute stress disorder and posttraumatic stress disorder
      in severely injured trauma survivors.
AB  - This prospective longitudinal study was designed to investigate the relationship
      between acute stress disorder (ASD) and the subsequent development of
      posttraumatic stress disorder (PTSD) in a population of severely injured
      hospitalised trauma survivors. Symptoms of ASD were assessed just prior to
      discharge in 307 consecutive admissions to a Level 1 Trauma Centre, with PTSD
      assessments completed at 3 and 12 months post-injury. A well-established
      structured clinical interview was adopted for both assessments. Only 1% of the
      sample met criteria for an ASD diagnosis (at a mean of 8 days post-injury), while
      the incidence of PTSD was 9% at 3 months and 10% at 12 months. Although all ASD
      symptom clusters contributed to the prediction of subsequent PTSD severity,
      logistic regression indicated that only re-experiencing and arousal predicted a
      categorical PTSD diagnosis. The dissociative symptoms that form the core of ASD
      were rarely endorsed and showed high specificity but low sensitivity, resulting
      in a high proportion of false negative diagnoses. Reducing the number of
      dissociative symptoms required for a diagnosis ameliorated, but did not resolve,
      the problem. In this particular population, the low sensitivity of the ASD
      diagnosis renders it a poor screening test for use in identifying high risk
      individuals for early intervention and prevention strategies.

PMID- 14975773
TI  - Autobiographical memories of anxiety-related experiences.
AB  - Ninety-nine undergraduate students retrieved three memories associated with each
      of the five emotional experiences: panic, trauma, worry, social anxiety, and
      feeling content. Subsequently, they answered 24 questions assessing properties of
      each memory, including the vividness and perceived accuracy of the memories and
      sensory, emotional, and anxiety-related experiences during retrieval. Memories
      were coded for affective tone and specificity. Results indicated that panic
      related and trauma-related memories were rated similarly as content memories, but
      that they generally were associated with more imagery and emotional experiencing
      than worry-related or social anxiety-related memories. Participants experienced
      panic and worry symptoms to the greatest degree when they retrieved panic-related
      and trauma-related memories. All anxiety-related memories were characterized by
      more negative tone than content memories. Panic-related and trauma-related
      memories were more specific than worry-related, social anxiety-related, and
      content memories. These findings can explain partially why individuals with some,
      but not all, anxiety disorders experience enhanced memory for threatening
      material.

PMID- 14975774
TI  - The effect of cues on young children's abilities to discriminate among thoughts,
      feelings and behaviours.
AB  - OBJECTIVE: To determine if cues help young children discriminate among thoughts,
      feelings and behaviours. PARTICIPANTS: Ninety-six children aged 4-7 years from
      three schools in Norwich, UK. DESIGN: Within each age band (4, 5, 6, 7), children
      were randomised to the cue or the no cue condition on a stratified basis ensuring
      that equal numbers of boys and girls from each school were in each of the eight
      cells (cue condition x age). Cues were glove puppets and post boxes. The effect
      of IQ was controlled. MEASURES: A discrimination task, in which children were
      asked to identify a thought, a feeling and a behaviour from each of six brief
      stories, and a brief IQ assessment were administered to children individually.
      RESULTS: There was a significant effect of age and cue condition on performance;
      older children and those who were presented with the cue performed better. There
      were no gender differences and no interaction between cue condition and age.
      CONCLUSION: Many young children discriminated among thoughts, feelings and
      behaviours suggesting that they may be able to engage in this aspect of cognitive
      behaviour therapy. Simple cues (puppets and posting boxes) improved children's
      performance and these may be useful therapeutic tools with young children.

PMID- 14975775
TI  - Cognitive-behavioural interventions in a patient with an anxiety disorder related
      to diabetes.
AB  - This study extends the data on the efficacy of cognitive interventions for
      patients with chronic medical problems and describes the case of a 37-year-old
      woman with an anxiety disorder related to diabetes. The effects on panic
      frequency, use of safety behaviour and related beliefs were investigated after
      the introduction of two main cognitive-behavioral interventions. The results are
      consistent with predictions from the cognitive model of panic. This case
      demonstrates the usefulness of directly challenging the 'meaning' of the feared
      situation in order to produce clinically significant improvements in the
      management of physical disease.

PMID- 14975776
TI  - Effects of aerobic exercise on anxiety sensitivity.
AB  - Anxiety sensitivity is a known precursor to panic attacks and panic disorder, and
      involves the misinterpretation of anxiety-related sensations. Aerobic exercise
      has been shown to reduce generalized anxiety, and may also reduce anxiety
      sensitivity through exposure to feared physiological sensations. Accordingly, 54
      participants with elevated anxiety sensitivity scores completed six 20-min
      treadmill exercise sessions at either a high-intensity aerobic ( n = 29 ) or low
      intensity ( n = 25 ) level. Self-ratings of anxiety sensitivity, fear of
      physiological sensations associated with anxiety, and generalized anxiety were
      obtained at pre-treatment, post-treatment, and one-week follow-up. Results
      indicated that both high- and low-intensity exercise reduced anxiety sensitivity.
      However, high-intensity exercise caused more rapid reductions in a global measure
      of anxiety sensitivity and produced more treatment responders than low-intensity
      exercise. Only high-intensity exercise reduced fear of anxiety-related bodily
      sensations. The implications of these findings are discussed.

PMID- 14975777
TI  - Acquired sensitivity to relevant physiological activity in patients with chronic
      health problems.
AB  - The hypothesis that biased symptom perception toward excessive symptoms is common
      when relatively normal chronic patients enter symptom-relating situations,
      irrespective of emotional variables, was tested in 19 women with severe asthma,
      18 with somatization-like characteristics, and 18 controls. Each underwent three
      experimental conditions: mental stress, resting, and physical exercise. Each
      condition included three breathing conditions: breathing normally, normal
      compressed air, and 5.5% CO2-enriched compressed air. Results yielded no group
      differences in physiological measures, e.g. elevated CO2 in exhaled air (end
      tidal partial pressure of CO2, PetCO2), or lung function. Asthma patients
      experienced more breathlessness, and somatization-like participants more
      breathlessness, miscellaneous symptoms, and subjective stress than controls.
      Although these differences suggested acquired biased symptom perception, as it
      turned out, breathlessness in asthmatics was more influenced by PetCO2 and less
      by subjective stress compared to controls. Likewise, breathlessness in
      somatization-like participants was similarly influenced by PetCO2 and subjective
      stress compared to controls, and miscellaneous symptoms were even more influenced
      by PetCO2 and less by subjective stress compared to controls. It was concluded
      that acquired sensitivity to physiological activity associated with habitual
      symptoms may account for excessive symptoms in patients with chronic health
      problems.

PMID- 14975778
TI  - Differentiating between memory and interpretation biases in socially anxious and
      nonanxious individuals.
AB  - Although individual cognitive biases toward threat in social anxiety are well
      established, few studies have examined the manner in which cognitive biases work
      in conjunction. In the present study, socially anxious ( n = 54 ) and nonanxious
      ( n = 58 ) individuals read 10 passages consisting of positive social or
      evaluative, negative social or evaluative, and neutral content and completed two
      cognitive tasks assessing memory of factual details and interpretation
      immediately and after 48 h. Socially anxious and nonanxious individuals did not
      differ in their memory for details presented in the passages. However, they made
      less positive and more negative interpretations of details included in the
      passages, particularly in positive passages that were self-relevant and
      particularly in positive passages after the delay. After including depression,
      state anxiety, and trait anxiety as covariates, biased interpretation of positive
      passages after the time delay remained significant, but biased interpretation of
      the self-relevant, positive passages did not. It is concluded that socially
      anxious individuals are characterized by accurate memory of threatening, factual
      material, but that they impose a biased interpretation upon that material,
      especially after some time has passed.

PMID- 14975779
TI  - Feelings of mental pollution subsequent to sexual assault.
AB  - This paper describes an investigation of the phenomenon of mental pollution in a
      sample of 50 female victims of sexual assault. Feelings of mental pollution were
      assessed using an interview and a questionnaire. An experimental procedure was
      employed to determine if feelings of dirtiness and the urge to wash could be
      provoked by deliberate attention to the assault memory. Thirty (60%) of the 50
      participants reported some feelings of mental pollution subsequent to the
      assault, and feelings of mental pollution were related to post-assault washing
      behaviour. Deliberate recall of the assault resulted in stronger feelings of
      dirtiness and the urge to wash than did deliberate attention to a pleasant memory
      or scene. Nine women reported washing their hands in response to deliberate
      recall of the assault. These findings suggest that feelings of mental pollution
      may be prominent in victims of sexual assault.

PMID- 14975780
TI  - Studies of the vicarious traumatization of college students by the September 11th
      attacks: effects of proximity, exposure and connectedness.
AB  - From mid-October 2001 through the end of November 2001, we collected fairly large
      sets of questionnaires from undergraduates at three public universities (Albany,
      NY, n = 507, Augusta, GA, n = 336, Fargo, ND, n = 526 ) to assess rate of acute
      stress disorder (ASD) and level of ASD symptoms following the September 11th
      attacks, rate of current posttraumatic stress disorder (PTSD) and level of PTSD
      symptoms, and current level of depressive symptoms resulting from the September
      11th attacks. We also gathered information on exposure to media coverage of the
      attacks, connectedness to the World Trade Center (WTC) and personnel there, and
      degree of engagement in reparative acts such as giving blood, attending vigils.
      We found higher levels of ASD, ASD symptoms, PTSD and PTSD symptoms as a function
      of geographical proximity to New York City (and within the Albany site, proximity
      of students' homes) and gender. Exposure (hours of TV watched) was a predictor in
      some instances as was connectedness to WTC victims. ASD symptoms were the
      strongest predictor of subsequent PTSD symptoms. Path models accounted for over
      60% of the variance in PTSD symptoms.

PMID- 14975781
TI  - Behavioral avoidance tests and disgust in contamination fears: distinctions from
      trait anxiety.
AB  - Much of the existing literature examining the role of disgust is limited to
      specific phobia. Recent research has begun to examine the role of disgust in
      contamination fear, a subtype of obsessive-compulsive symptoms. Through the use
      of behavioral avoidance tasks (BATs), the current study was designed to examine
      the role of disgust in people with contamination fears, with attention to
      distinguishing high and low trait anxiety. From a large screening of
      undergraduate students, three groups were formed based on their level of
      contamination fear and level of trait anxiety: contamination fearful ( n = 12 ),
      high-trait anxiety ( n = 11 ), and low trait anxiety ( n = 15 ). Subjects were
      asked to engage in six different BATs corresponding to six domains of disgust
      (food, animals, body products, body envelope violations, death, and sympathetic
      magic). One-way analysis of variance (ANOVA) showed significant differences
      between the contamination fearful group and the high trait anxiety group on the
      animal and sympathetic magic BATs. Significant differences on the food, animal,
      body envelope violations, and death BATs were also found between the
      contamination fearful group and the low-trait anxious group. The findings
      modestly support the importance of disgust in contamination fears. Implications
      for the study of disgust in contamination fear are provided.

PMID- 14975782
TI  - Positive schizotypal symptoms predict treatment outcome in obsessive-compulsive
      disorder.
AB  - Previous research has suggested that the presence of schizotypal personality
      disorder may represent a risk factor for treatment failure in obsessive
      compulsive disorder (OCD). Relying on a dimensional approach, the present study
      investigated whether the predictive importance of schizotypal personality is
      shared by all of its features to the same extent or whether it is confined to a
      subset of symptoms. Fifty-three patients underwent multi-modal cognitive
      behavioral therapy with or without adjunctive antidepressive medication. Therapy
      response was defined as a 35% decline of the Y-BOCS total score. At baseline
      assessment, patients were asked to fill out the schizotypal personality
      questionnaire, the perceptual aberration scale and the Beck depression inventory.
      Stepwise regression analysis and group comparisons conducted with the schizotypal
      and depression scales revealed that elevated scores in the positive schizotypal
      scales, especially perceptual aberrations, were highly predictive for treatment
      failure. Responders to treatment and non-responders did not significantly differ
      on other variables or on scores in two scales which measured response biases. The
      study provides evidence that positive schizotypal symptoms are antecendents for
      treatment failure in OCD. It needs to be evaluated whether these at-risk
      individuals benefit from additional intervention, such as the adminstration of
      low-dose atypical neuroleptics and specifically tailored behavorial intervention.

PMID- 14975783
TI  - Treatment of acrophobia in virtual reality: the role of immersion and presence.
AB  - In this study the effects of virtual reality exposure therapy (VRET) were
      investigated in patients with acrophobia. Feelings of presence in VRET were
      systematically varied by using either a head-mounted display (HMD) (low presence)
      or a computer automatic virtual environment (CAVE) (high presence). VRET in
      general was found to be more effective than no treatment. No differences were
      found in effectiveness between VRET using an HMD or CAVE. Results were maintained
      at 6 months follow-up. Results of VRET were comparable with those of exposure in
      vivo (Cyberpsychology and Behavior 4 (2001) 335). In treatment completers no
      relationship was found between presence and anxiety. Early drop-outs experienced
      less acrophobic complaints and psychopathology in general at pre-test. They also
      experienced less presence and anxiety in the virtual environment used in session
      one as compared to patients that completed VRET.

PMID- 14975784
TI  - The factor structure of the Anxiety Sensitivity Index among Northern Plains
      Native Americans.
AB  - Within our current research climate, an emphasis has been placed on examining the
      cross-cultural applicability of psychological tools, and exploring their utility
      with people of different backgrounds. Within this line of investigation lies the
      risk of classifying people too broadly and masking important regional, tribal, or
      dialectical differences. This may be particularly potent among Native Americans,
      given the number of distinct indigenous entities. This study examined the
      psychometric characteristics of the Anxiety Sensitivity Index with a tribally
      homogeneous sample, as compared to previous tribally-heterogeneous and majority
      culture findings. Results suggested that data from a homogeneous Native American
      sample poorly fit factor solutions reported from heterogeneous Native American
      and Caucasian samples, and favored a unifactorial solution. Implications for
      assessment with Native American peoples are discussed.

PMID- 14975785
TI  - Hypothalamic hamartoma and epilepsy: the pathway of discovery.

PMID- 14975786
TI  - The anatomy and embryology of the hypothalamus in relation to hypothalamic
      hamartomas.
AB  - The hypothalamus is involved in a variety of autonomic, endocrine, neurological
      and behavioural functions including temperature, osmostatic and autonomic nervous
      system regulation, pituitary, thyroid, adrenal and gonadal control, thirst,
      appetite and weight control, memory and emotional behaviour including aggression
      and laughter, and biological (circadian) rhythms. The functional anatomy of the
      hypothalamus and its major afferent and efferent neurological connections are
      described, with particular reference to hypothalamic hamartomas (HH), gelastic
      seizures, MRI of the hypothalamus, and potential effects of surgery for HH.
      Normal development of the hypothalamus is reviewed in relation to models of
      forebrain development, descriptive hypothalamic embryology and the importance of
      known transcription factors. Potential environmental antecedents to HH
      development are discussed, and the significance for sporadic, isolated HH of
      several syndromes associated with HH is explored.

PMID- 14975787
TI  - Hypothalamic hamartoma and epilepsy in children: illustrative cases of possible
      evolutions.
AB  - The progresses of neuroimaging have allowed an earlier detection of hypothalamic
      hamartoma in children presenting with gelastic or dacrystic seizures. Associated
      symptoms can include other types of seizures, precocious puberty, and behavioral
      or cognitive deterioration. Combination of all these features is not constant
      and, when present, their evolution may be variable. When epilepsy proves
      intractable, surgery may be a solution but is not without risks. Therefore, it
      can only be justified on the basis of a considerable degree of certainty on the
      progressive character of the disorder, both in terms of epilepsy and global
      development. Even though epilepsy is a major and usually the most important
      problem, it is not always possible to predict its course and to be able to
      evaluate its potential effects on development. Available data suggests that
      deterioration is partly related to the epileptogenic activity. We reviewed data
      from 16 personal cases and discussed the possible evolutions of the epilepsy
      syndrome on the basis of 6 illustrative cases and a review of the literature. We
      point out that seizures may start early in life and evolve either towards a
      catastrophic encephalopathy or may be transiently severe and will progressively
      settle down. Intermediate situations also exist as well as cases presenting with
      a mild epilepsy. In almost all cases cognitive difficulties are present and may
      be associated with behavioral disturbances. They are of variable severity,
      usually in relation to the severity of the epilepsy and the evolution of the EEG
      abnormalities. Some of our cases also illustrate that, in young children whose
      seizures are limited to "a sensation of a pleasant feeling", "a pressure to
      laugh" or "smiling", early detection of the hamartoma may still be difficult and
      the epilepsy pattern may be misdiagnosed as an epilepsy temporal or frontal
      origin. Detailed analysis of the electro-clinical evolution of representative
      cases highlights the variable expression of the epilepsy syndrome and renders
      difficult any dogmatic position on early surgery. However, recent data suggests
      that a surgical solution must be sought early. Prospective studies are needed to
      evaluate, not only outcome in terms of control the seizures without unacceptable
      side effects but also on the evolution of the cognitive and behavioral profile of
      children with HH and epilepsy are needed.

PMID- 14975788
TI  - Hypothalamic hamartoma in adults.
AB  - Epilepsy in adult patients with hypothalamic hamartoma has not been well studied.
      It is uncommon but merits recognition. In this paper, 14 adult patients with
      hypothalamic hamartoma and epilepsy, of whom three developed epilepsy only in
      adult life, are presented. The later onset of epilepsy appears to be associated
      with a milder epilepsy syndrome, less severe learning difficulties and behaviour
      problems, and better occupational and social status. Gelastic seizures are less
      prominent in this age group. Of particular interest, one patient had prominent
      sleep disturbances characterized by a reduction in total slow wave and REM sleep
      without daytime sleepiness. The milder epilepsy and preserved cognitive and
      social functioning have implications for management. A number of patients were
      controlled by anticonvulsant medication, and were functioning satisfactorily. For
      such patients minimally invasive surgical procedures, or medical therapy should
      be considered.

PMID- 14975789
TI  - From hypothalamic hamartoma to cortex: what can be learnt from depth recordings
      and stimulation?
AB  - Patients having a hypothalamic hamartoma (HH) frequently present gelastic or
      dacrystic seizures, and they often later experience multiple additional seizure
      types which lead to a severe epileptic encephalopathy. There is now increasing
      evidence that the HH itself plays a crucial role in this syndrome, but the
      relationships between the lesion and the different types of seizures remain a
      questionable issue. Stereotactic intracerebral EEG recordings were performed in 5
      patients suffering from a medically intractable epilepsy associated with a HH.
      The hamartoma was investigated in all cases, and various cortical areas were also
      evaluated in 4 of the 5 patients. The epileptic discharges arose and remained
      confined within the hamartoma in 3 of the 4 patients in whom laughing and crying
      episodes were recorded. In addition, interictal spikes were recorded from the
      hamartoma in 4 of the 5 patients, whereas the stimulation of the HH could
      reproduce gelastic or dacrystic episodes in 3. The three patients in whom other
      types of seizure were recorded showed that the latter were associated with
      cortical ictal discharges not affecting the HH. Ictal onset appeared either
      bifrontal, right fronto-central and lateral temporal, or bifrontal with a right
      side predominance. The cingulate gyrus was involved in all these 3 cases, and the
      lateralization of the ictal discharges was always ipsilateral to the
      predominating side of the hamartoma. Interestingly, these seizure types were
      sometimes immediately preceded by the laughing or crying attacks, as if ictal
      discharges within the hamartoma triggered those which seemed to originate in the
      cortex. Therefore, if these findings confirm the intrinsic epileptogenicity of
      HH, they also demonstrate that epileptic seizures associated with HH can exhibit
      different types of electroclinical patterns. We propose a speculative
      pathophysiology in which the mamillo-thalamo-cingulate tract would serve as a
      relay of HH discharges towards the cortex, the excitability of which would then
      progressively increase, first leading to cortical interictal epileptiform
      abnormalities and then to seizures of cortical origin. Whether this proposal of
      secondary epileptogenesis is valid or not remains a major issue, since it could
      provide arguments on the moment to discuss surgery.

PMID- 14975790
TI  - Positron emission tomography in epileptogenic hypothalamic hamartomas.
AB  - Whether the intrinsic epileptogenicity of hypothalamic hamartomas (HH) is
      responsible for the entire clinical spectrum of epileptic, neuropsychological and
      behavioural disorders associated with HH, remains an open issue, in as much as
      morphologically similar HH can be associated with dramatically different seizure
      types and cognitive outcomes. The aim of this study was to investigate brain
      glucose metabolism in patients with epileptogenic HH, in an attempt to identify
      signs of focal cortical and subcortical dysfunction which might correlate with
      other clinical data. We have studied five patients with epileptogenic HH using
      [18F]-fluoro-desoxyglucose and positron emission tomography (FDG-PET). All our
      patients also underwent an optimal MRI and a video-EEG monitoring, as well as an
      intra-cranial EEG recording in one of them. The anatomical distribution of FDG
      PET abnormalities was compared to that of interictal and ictal electroclinical
      findings. All five patients demonstrated focal hypometabolism, ipsilateral to the
      predominant EEG abnormalities and side of HH. Hypometabolic areas greatly varied
      between patients, but were grossly concordant with the cortical regions suspected
      to participate in the ictal discharges in each individual. Epileptogenic
      hypothalamic hamartomas are usually associated with focal cortical hypometabolism
      in regions which might participate in the overall HH-driven epileptic network.
      Whether these cortical abnormalities only reflect the propagation of ictal
      discharges, or a potentially independent seizure onset zone remains unknown.

PMID- 14975791
TI  - Psychiatric aspects of patients with hypothalamic hamartoma and epilepsy.
AB  - Uncontrolled rage, while long associated with hypothalamic hamartoma, has not
      been as extensively studied as the epilepsy. Rage can be more detrimental to
      quality of life than seizures. It is now realized that behavior and aggression
      improve after a complete resection of the hypothalamic hamartoma correlating with
      a good seizure control post-surgically. We report on the longitudinal psychiatric
      history of a patient with hypothalamic hamartoma and rage whose severe and
      refractory epilepsy was ultimately treated by thalamic and intrahamartoma chronic
      stimulation. Our patient did not exhibit sham rage typical of hypothalamic
      lesions, but rather multifactorial aggressive bouts typical of challenging
      behaviors seen with mental retardation. The anxious and social features of the
      aggression suggest that psychiatric interventions, which have been neglected as
      the emphasis has been on seizure control, are worthwhile in the overall
      management of this difficult case.

PMID- 14975792
TI  - Heritable syndromes with hypothalamic hamartoma and seizures: using rare
      syndromes to understand more common disorders.
AB  - Manifestations of non-syndromic hypothalamic hamartomas are different from those
      of the syndromic hamartomas, and the syndromic ones are rare. In spite of the
      rarity of the syndromic hamartomas, they can be a powerful biological tool to
      help us understand the pathophysiology of these heritable disorders. Several
      disorders that include hypothalamic hamartomas are reviewed here and the current
      understanding of the biology of the lesions is summarized.

PMID- 14975793
TI  - The endocrinology of hypothalamic hamartoma surgery for intractable epilepsy.
AB  - Intractable epilepsy has replaced central precocious puberty (CPP) as the main
      indication for surgery in patients with hypothalamic hamartoma (HH). However,
      concern about endocrine complications and the paucity of published endocrine data
      may dissuade clinicians from recommending HH surgery. We report the preoperative
      endocrine status and postoperative endocrine findings of patients undergoing HH
      surgery at our centre. Twenty-nine patients aged 4-23 years (mean 10 years)
      underwent detailed clinical assessment and biochemical testing of the
      hypothalamic-pituitary axis before and after transcallosal resection of their HH.
      The perioperative evaluation included comprehensive evaluation of pubertal
      status, growth, weight, thyroid and adrenal function, and osmoregulation. Forty
      five percent of patients had CPP at presentation and this was not altered by HH
      surgery. Asymptomatic deficiencies in thyroid hormone, growth hormone and
      cortisol response were identified in several patients prior to surgery, and
      biochemical CPP was present in four, clinically prepubertal children. Free
      thyroxine fell after surgery in the majority, and to clinically significant
      levels prompting treatment in 5 patients. Low growth hormone was present in 5/8
      patients who had had previous HH surgery and in 6/29 following transcallosal
      surgery at our centre; short stature did not result during the period of follow
      up. Hypernatraemia developed in most patients postoperatively with sodium >150
      mmol/L seen in 16 (55%) patients; however, this was asymptomatic, not often
      associated with polyuria, and transient; no patient required ongoing antidiuretic
      hormone replacement. Appetite stimulation and early postoperative weight gain
      occurred in 45% patients, but resolved in half. Disturbance of endocrine function
      may be clinically silent and should be routinely evaluated prior to HH surgery
      for intractable epilepsy. Following surgery, hypernatraemia, low thyroxine, low
      growth hormone, and weight gain are the main endocrine problems encountered.
      Prior, unsuccessful surgery may be a risk factor for endocrinopathy. Except for
      weight gain in some patients, these postoperative endocrine disturbances appear
      to be transient, mild or asymptomatic, and easily treated where necessary. Long
      term follow-up of growth and sexual development in a large series of patients is
      required.

PMID- 14975794
TI  - The treatment of patients with hypothalamic hamartomas, epilepsy and behavioural
      abnormalities: facts and hypotheses.
AB  - The growing interest in the association between hypothalamic hamartomas (HH),
      epilepsy and behavioural abnormalities witnessed in recent years, has led to
      significant progress regarding the clinical presentations, pathophysiology and
      management of this entity. Patients with these lesions may occupy different
      points within a spectrum of severity of the epileptic and behavioural disorder,
      and may dynamically progress toward more malignant epilepsies with time. The role
      of the subcortical lesion in the generation of the gelastic seizures has been
      established, and encouraging results have been obtained with surgical resection,
      destruction or disconnection of the hamartoma. The present work highlights
      several aspects that should be taken into account for the selection of medical
      and surgical treatment for individual patients. We conclude with a reflection on
      what we still do not understand as regards in the genesis and surgical management
      of the neuropsychiatric disabilities related to this disorder.

PMID- 14975795
TI  - Transcallosal resection of hypothalamic hamartomas in patients with intractable
      epilepsy.
AB  - A variety of surgical treatments for intractable epilepsy with hypothalamic
      hamartoma (HH) are described, although most are derived from limited patient
      experience gathered from several centres. We describe the results of
      transcallosal resection of HH in 29 consecutive patients undergoing surgery at
      one centre. Twenty-nine patients aged 4-23 years (mean 10 years) underwent HH
      surgery with a minimum of 12 months follow-up. A comprehensive, presurgical
      epilepsy evaluation, supplemented with endocrine and ophthalmological assessments
      was performed in all cases. HH were resected via a transcallosal, interforniceal
      approach to the third ventricle, with the assistance of frameless stereotaxy,
      limiting the resection to the margins of the third ventricular walls and floor
      and minimising traction and diathermy. Complete or near-complete (>95%) resection
      of the HH was achieved in 18/29 patients, 75-95% resection was achieved in seven
      patients (four of whom had complete or near-complete disconnection of residual
      HH) and less than 50% resection was achieved in four. Postoperatively (follow-up
      12-70 months, mean 30 months), 15 became seizure-free (nine off antiepileptic
      medication), seven had >90% reduction in seizure frequency, three had 55-80%
      reduction in seizure frequency, and four had less than 40% reduction in seizure
      frequency. Of 16 patients who had seizures in the early postoperative period, six
      became seizure. No patient or lesion characteristics were associated with
      postoperative seizure freedom, including features of symptomatic generalised
      epilepsy. Neurobehavioural improvement and resolution of EEG abnormalities were
      seen in the majority. Complications were transient hemiparesis in two, transient
      hypernatraemia in 17, short-term memory impairment in 14 (persistent in four),
      weight gain in ten (persistent in five), need for supplemental thyroxine in five,
      and lowered growth hormone (uncertain clinical significance) in six.
      Transcallosal resection of HH is an effective treatment for intractable epilepsy,
      with 76% patients in our seizures being seizure-free or having >90% seizure
      reduction. The operative risks include stroke, short-term memory disturbance,
      weight gain and minor endocrine disturbances. Based on published data, the
      transcallosal approach appears to be safer and more effective than other
      operative strategies.

PMID- 14975796
TI  - Hypothalamic hamartoma with refractory epilepsy: surgical procedures and results
      in 18 patients.
AB  - AIM: To study the surgical procedures and results on seizures, in 18 patients
      with refractory epilepsy due to hypothalamic hamartoma. PATIENTS AND METHODS:
      Eighteen patients aged from 9 months to 32 years underwent surgery between 1997
      and 2002. The mean age at seizure onset was 15.5 months. Seventeen patients had
      gelastic seizures, 14 had partial seizures, two had infantile spasms, 10 had
      tonic or atonic seizures and three had generalized seizures. The mean seizure
      frequency was 21 per day. Four patients had borderline intellectual disability
      and the others were mentally retarded. Five patients had precocious puberty, one
      had acromegaly and four suffered from obesity. Brain MRI, performed at least
      twice in each patient showed the hamartoma as a stable, homogeneous
      interpeduncular mass implanted either on the mammillary tubercle or on the wall
      of the third ventricle, with variable extension to the bottom. Ictal SPECT,
      performed in four patients, showed hyperperfusion within the hamartoma in two.
      SURGICAL PROCEDURE: Twenty-six operations were performed in 18 patients. The
      first patient underwent a total removal of the hamartoma, whereas the following
      patients underwent a disconnection, either through open surgery (14 patients) or
      endoscopy (10 patients). RESULTS: Regarding the seizure outcome with a mean
      follow up of three years four months (one year to 4.5 years), nine patients are
      seizure-free, one patient has only brief gelastic seizures and eight are
      dramatically improved. Surgery was uncomplicated in all but two patients: one had
      transitory hemiplegia and paresis of the third cranial nerve, the other presented
      with hemiplegia due to ischemia of the middle cerebral artery territory. The
      quality of life, behavior and school performance were greatly improved in most of
      the patients. CONCLUSION: Our series illustrates the feasibility and relative
      safety of disconnecting surgery of hypothalamic hamartomas, with seizure relief
      in 50% and a dramatic improvement in the others. Endoscopic disconnection seems
      to be a very safe way to treat the intra-ventricular part of hamartomas.

PMID- 14975797
TI  - Stereotactic surgical approach to hypothalamic hamartomas.
AB  - Hypothalamic hamartomas are often associated to a progressive epileptic
      encephalopathy. Non-invasive data indicates that destruction or isolation of the
      hamartoma may stop seizures. We present data on patients who underwent
      stereotactic radiofrequency with or without endoscopy. Epilepsy improved in 60%
      of patients with minimal morbidity. This approach was less successful in large
      lesions. These results indicate that this approach should be considered in
      patients with small/medium lesions.

PMID- 14975799
TI  - [Oncologically speaking, are our countrywomen and countrymen in good health?].

PMID- 14975798
TI  - Resective surgery for hypothalamic hamartoma.
AB  - Hypothalamic hamartoma presents with precocious puberty, epilepsy or both. There
      are two epileptic syndromes, one presenting initially in infancy with gelastic
      seizures evolving rapidly into a syndrome with multiple seizures, developmental
      delay and a moderate to severe behaviour disorder. The other presents later with
      a milder epileptic syndrome, again usually including gelastic seizures, but with
      normal intellect and behaviour. Magnetic resonance imaging identifies and gives a
      detailed anatomical picture of these lesions. Direct surgery, using microsurgical
      techniques and neuronavigation guidance has been used for these lesions. Three
      surgical approaches have been used, one lateral pterional, another midline
      frontal through the lamina terminalis and a third is a transcallosal
      interforniceal approach. In addition a disconnection procedure, usually
      pterional, aims to disconnect the lesion without the risks of major resection.
      The transcallosal interforniceal approach is the most successful with 69% of
      patients seizure-free. There are complications in about 24% of patients, the same
      as other approaches, but the complications are milder and include fewer
      neurological deficits than the other routes. Alternate strategies include
      stereotactic radiosurgery and radiofrequency ablation under stereotactic control.

PMID- 14975800
TI  - [Frequency of cancer in France: 2004 update].
AB  - The most recent cancer mortality and morbidity data available for France are
      presented. In 1999, cancers are the first cause of death among men (87,000
      deaths) and the second most common among women (57,000 deaths) after
      cardiovascular diseases. Lung cancer is the most common cause of cancer death
      (21,000) in the male population, and breast cancer is the most common cause of
      death (11 000) in the female population. Cancer mortality rates decrease both in
      the male population since 1987 and in the female population since 1950, but the
      different sites present different trends. The total number of cancers diagnosed
      in 2000 is estimated to be equal to 280,000, 160,000 in the male population and
      120,000 in the female population. The most frequent cancer sites are prostate
      among men (40,000 cases) and breast among women (42,000 cases), two sites for
      which screening activities are in widespread use. The tobacco-related lung cancer
      epidemic is accelerating markedly in the female population and is beginning to
      decrease in the male population.

PMID- 14975801
TI  - [RNA interference and its possible use in cancer therapy].
AB  - Post-transcriptional gene silencing (PTGS) or RNA interference (RNAi) is a
      powerful tool for silencing gene expression. This mechanism was initially
      considered as a strange phenomenon limited to few plant species. It has become
      clear that PTGS occurs in both plants and animals and has roles in viral defense
      and transposon silencing mechanisms. However, the use of RNA interference
      triggered by the introduction of small double-stranded RNA (dsRNA or siRNA) into
      mammalian cells as a tool to knock down expression of specific genes holds the
      promise to selectively inhibit expression of disease-associated genes in humans.
      On the other hand, there are about 40,000 protein-coding genes in the human
      genome, but the function of most of them remains unknown. RNAi technology has now
      been developed for systematically deciphering the functions and interactions of
      these thousands of genes.

PMID- 14975802
TI  - [Recent advances in pharmacogenomics in oncology].
AB  - Progress in understanding the molecular mechanisms of oncogenesis, together with
      the sequencing of the human genome and the availability of huge databases, bring
      new tools for the discovery and the evaluation of new potential targets for
      cancer therapy and for the individualisation of cancer chemotherapy as a function
      of the molecular characteristics of tumours. Targeting the genetic alterations of
      cancer cells appears feasible and the first successes of this approach allow to
      remain optimistic about the renewal of our therapeutic armamentarium. In
      addition, seeking for correlations between gene expression profiles and
      chemosensitivity has been performed on the in vitro models of the National Cancer
      Institute and may allow crucial improvements in the identification of patients
      who world best take advantage of a specific chemotherapy. Clinical trials, first
      on a retrospective basis, then performed prospectively, are implemented to
      validate this approach.

PMID- 14975803
TI  - [Cytogenetics, cytogenomics and cancer: 2004 update].
AB  - Cytogenetics has clearly established the key role chromosomal rearrangements play
      in neoplastic initiation and progression. Investigation methods have evolved
      considerably from banding analysis of chromosome morphology to fluorescence in
      situ hybridization (FISH) and now to comparative genomic hybridization (CGH) on
      chromosomes or micro-array analysis of DNA. In addition to its contributions to
      the description, prognosis and understanding of oncogenesis and tumor
      progression, cytogenomics provides the information required for the rational use
      of new targeted therapies among which Imatimib is the most achieved example.

PMID- 14975804
TI  - [Optical diagnosis of cervical dysplasia].
AB  - Cervix cancer is a curable disease when diagnosed at an early stage. Screening of
      cervical lesions by cytology and colposcopy with in situ staining has allowed for
      substantial progress in early diagnosis and consequently the cure of cervix
      cancer. Nevertheless, because of its low specificity, this approach generally
      implies repetitive tissue sampling and, thus a relative long time before the
      treatment of the lesions. Furthermore, the cost of preparation and analysis of
      biopsy samples is sufficiently high to represent a burden for industrialized
      countries and a virtual impossibility for the developing world. To overcome these
      problems, various biophotonic methods using optical fibers have been developed to
      allow for detection of cervical epithelial anomalies in a specific, fast and non
      invasive way. This process, known as "optical biopsy", is based on the
      measurement of light-tissue interactions, which are analysed by various
      mathematical and data processing methods, to provide information on the
      metabolism and morphology of epithelial tissue. Currently investigated methods
      can be distinguished according to the type of signal used to probe the tissue
      (fluorescence, reflectance), the depth of analysed tissue (surface analysis,
      confocal imaging, tomography), the analysis modalities (spectral measurements or
      imaging), and the use of additive molecules (contrasting or photosensitizing
      agents, inorganic fluorophores). While most of the methods remain experimental,
      constant progress in the understanding of the mechanisms of light behavior in
      biological environments as well as advances in optical fibers technology, will
      make a number of these methods soon available for clinical practice to contribute
      efficiently to the reduction of biopsy number and cost of cervical screening.

PMID- 14975805
TI  - [Neoadjuvant endocrine therapy for breast cancer: an overview].
AB  - The clinical benefits of endocrine therapy for patients with hormonosensitive
      breast cancer remains perfectly established. For instance, tamoxifen, the gold
      standard of the adjuvant treatment, has largely contributed of the effectiveness
      of such a therapy. The recent development of new endocrine agents (the third
      generation aromatase inhibitors, selective estrogen receptors modulators),
      provides to physicians the opportunity of a more effective and tolerable
      therapeutic approach, in the metastatic disease setting or likely in adjuvant
      setting for breast cancer patients. Preoperative therapy has been widely used for
      the treatment of initially inoperable locally advanced breast cancers with the
      main objective of breast-conserving surgery. The benefits of neoadjuvant
      chemotherapy has widely been demonstrated; however, the success of neoadjuvant
      endocrine therapy is much recent. The clinical and pharmacological data of the
      main published studies using neoadjuvant hormonotherapy are presented herein this
      review. Therefore, clinical and histologic assessments of response brings
      essential informations about the breast cancer hormonal sensitivity, but may also
      be predictor of the future (adjuvant or metastatic) treatment responsiveness.

PMID- 14975806
TI  - [Adjuvant chemotherapy in non-small cell lung cancer].
AB  - Lung cancer is the leading cause of cancer death in France. Nearly 80% of lung
      tumors are non-small cell lung cancers (NSCLC). Surgery is the best curative
      approach, but it only concerns 30% of NSCLC, since the diagnosis is frequently
      made in patients with locally advanced or metastatic disease. Even when surgery
      is performed relapse occurs in up to 50% of patients. Several adjuvant trials
      have been led in the late 90's after an individual data-based meta-analysis
      suggested a 5% survival benefit at 5 years. Among those, the IALT study, with 1
      867 patients included, confirms the benefit of post-operative chemotherapy in
      resected NSCLC. In this article, the current status of adjuvant chemotherapy is
      reviewed, and future prospects are discussed.

PMID- 14975807
TI  - [Hormone therapy for prostate cancer].
AB  - Hormonal deprivation has been used for more than 60 years in the treatment of
      advanced prostate cancer However, the optimal form of this therapy is still an
      enigma. This review discusses some of the current challenges in the hormonal
      management of prostate cancer, regarding complete androgen blockade, intermittent
      treatment and the question of whether early hormonal deprivation is superior to
      delayed therapy. The choice of hormone therapy for cancer of the prostate depends
      not only on the desired progression free survival and overall survival but also
      an the patient's quality of life and on the treatment toxicities and costs.

PMID- 14975808
TI  - [Colon cancer: what is new in 2004?].
AB  - Two thousand and three was a particularly dense year for publications and
      communications on therapy for colon cancer summarizing the real advance performed
      in this field. The last ten years allowed a rapid evolution for colon
      chemotherapy with a switch from 5-FU modulated by leucovorin to poly-chemotherapy
      (fluoropyrimidines with oxaliplatin or irinotecan) integrated into therapeutic
      strategies, where surgery had a place more and more important in metastatic
      patients. In correlation with these advances, median survival of patient with
      metastatic colorectal cancer is between 17 and 22 months. Targeted therapeutics
      with monoclonal antibody such as EGF inhibitors (cetuximab) or VEGF inhibitors
      (bevacizumab) had for the first time demonstrated efficacy with encouraging
      results in randomised trials. In adjuvant situation, LV5FU2 is less toxic than
      monthly FUFOL and no statistically significant difference could be detected in
      disease-free or overall survival between the two schedules. Oxaliplatin combined
      with 5 fluorouracil and leucovorin (FOLFOX4) is the first combination to
      demonstrate significant superiority over 5 fluorouracil and leucovorin in
      adjuvant treatment of colorectal cancer. Fluorouracil-based adjuvant chemotherapy
      benefited to patients with stage II or III colon cancer with microsatellite
      stable tumours or tumour exhibiting low-frequency microsatellite instability but
      may be not those with tumours exhibiting high-frequency microsatellite
      instability (MSI). These data need to be confirmed by prospective studies before
      changing our therapeutic references. The number of lymph nodes analyzed for colon
      cancer staging is itself a prognostic variable on outcome. Laparoscopic surgery
      of colon cancer is demonstrated as a feasible and safe procedure. Shrinkage of
      tumours after administration of preoperative chemotherapy and availability of
      ablative techniques (radiofrequency and cryotherapy) now allow to treat with
      curative intent metastases initially considered as non-resectable.

PMID- 14975809
TI  - [Radiosurgery of brain metastasis: reflexions, controversies and unanswered
      questions in 2004].
AB  - The quantity of results published since the development of the radiochirurgie
      does not always lead to consider overall the consequences of the introduction of
      this treatment into the therapeutic arsenal of the clinician. The role of this
      treatment in front of the surgery, its association with the whole brain radiation
      therapy, the impact on the survival of this treatment and the incorporation of
      the various prognostic factors to the therapeutic decision are some one of the
      unresolved question. Best indications of radiosurgery concern probably patient
      with a good performance status, without extra-cranial disease and presenting no
      more than 4 metastasis. However, in an obviously palliative context, any
      dogmatism must be avoided. Development of prospective trials is the best solution
      to well specify the indication of the technique.

PMID- 14975810
TI  - [What's new in the treatment of cancer pain?].
AB  - Improvements have been made recently in the treatment of cancer pain. First of
      all, this symptom is better recognized and evaluated in cancer patients. Then new
      therapeutic options have became available in France : tramadol, WHO level II
      analgesic, for intermediate to severe pain; gabapentine, a new anticonvulsivant
      drug, for neuropathic pain; oral transmucosal fentanyl citrate for breakthrough
      pain; hydromorphone and oxycodone, morphine agonists, as an alternative to
      morphine; development of patient controlled analgesia via portable pump; better
      evaluation of alternative therapeutics.

PMID- 14975811
TI  - [Psycho-oncology and the present tasks of psycho-oncologists].
AB  - This article aims to contribute to a better apprehension by oncologists of the
      work done by psycho-oncologists, by diminishing misconceptions and
      misunderstandings end promoting collaboration between them. First, we describe
      the main aspects of their practice, which is still too poorly apprehended, the
      landmarks they use (when they support a patient they take into account his/her
      body, social and professional position, personal and family history, objectives,
      psychopathology and the family), and the tools they have at their disposal. We
      then describe how psycho-oncology is currently organised, the "players" in the
      field and their allies (oncology on one side, social and human sciences on the
      other) and the main practice and research themes as reported in recent congresses
      and articles. More and more psychotherapeutic groups, community support, the
      patient's social, cultural and ethnic specificity and family, information,
      genetic issues, burn out among care providers, and children are being considered
      important. We hope this article gives a true image and a sufficiently detailed,
      though not exhaustive, account of psycho-oncology today, of the range of its
      possibilities, of its central interests.

PMID- 14975812
TI  - Gas exchange and dry matter allocation responses to elevation of atmospheric
      CO(2) concentration in seedlings of three tree species.
AB  - Photosynthetic rates of 13-month-old Pinus radiata D. Don, Nothofagus fusca (Hook
      f.) Orst. and Pseudotsuga menziesii (Mirb.) Franco seedlings grown and measured
      at elevated atmospheric concentrations of CO(2) (~620 microl l(-1)) were 32 to
      55% greater than those of seedlings grown and measured at ambient (~310 microl l(
      1)) concentrations of CO(2). Seedlings grown in ambient and elevated
      concentrations of CO(2) had similar rates of photosynthesis when measured at ~620
      microl l(-1) CO(2), but when measured at ~310 microl l(-1) CO(2), the P. radiata
      and N. fusca seedlings which were grown at elevated CO(2) had lower rates of
      photosynthesis than the seedlings grown at an ambient concentration of CO(2).
      Stomatal conductances in general were lower when measured at ~620 microl l(-1)
      CO(2) than at ~310 microl l(-1) CO(2). Stomatal conductances declined in all
      species grown at both CO(2) concentrations when the leaf-air water vapor
      concentration gradient (DeltaW) was increased from 10 to 20 mmol H(2)O mol(-1)
      air. The percent enhancement in photosynthesis for P. radiata and P. menziesii at
      elevated CO(2) was greater at 20 mmol than at 10 mmol DeltaW, suggesting that
      elevated CO(2) may moderate the effects of atmospheric water stress. Dry matter
      allocation patterns were not significantly different for plants grown in ambient
      or high CO(2) air.

PMID- 14975813
TI  - Carbon allocation, root exudation and mycorrhizal colonization of Pinus echinata
      seedlings grown under CO(2) enrichment.
AB  - Increased exudation of carbon compounds from roots may provide a mechanism for
      enhancement of nutrient availability to plants growing in a CO(2)-enriched
      atmosphere. Therefore, the effect of atmospheric CO(2) concentration on carbon
      allocation and root exudation was investigated in Pinus echinata Mill. (shortleaf
      pine) seedlings. After 34 and 41 weeks, seedlings growing in 695 microl l(-1)
      CO(2) allocated proportionately more (14)C-labeled photosynthate to fine roots
      than did seedlings growing in ambient air. This was associated with greater fine
      root mass and mycorrhizal density in CO(2)-enriched plants after 34 weeks.
      Exudation of soluble, (14)C-labeled compounds from roots also was greater in
      these plants at 34 weeks, but the effect of CO(2) concentration on exudation did
      not persist at 41 weeks.

PMID- 14975814
TI  - Effects of low night temperature and light on chlorophyll fluorescence of field
      grown seedlings of Scots pine (Pinus sylvestris L.).
AB  - In vivo chlorophyll fluorescence kinetics was observed in naturally regenerated
      and planted Scots pine (Pinus sylvestris L.) seedlings growing at two adjacent
      sites in northern Sweden. Some seedlings were shaded from direct solar radiation
      and some were protected from frost at night. Air temperature and solar radiation
      were monitored. In vivo chlorophyll fluorescence kinetics of current-year needles
      was measured at both room temperature and 77 K. On clear days during August,
      variable fluorescence of photosystem II of needles from exposed, naturally
      regenerated seedlings was reduced by night frosts, whereas frost caused little
      change in fluorescence of needles from shaded seedlings. Overnight frost
      protection reduced the inhibition of photosystem II by direct sunlight. Recovery
      from photoinhibitory damage occurred on cloudy days. In September, the decline of
      variable fluorescence of photosystem II was more pronounced in unshaded than in
      shaded seedlings, and coincided with frosts at night. In addition, the reduction
      in variable fluorescence was larger for planted seedlings than for naturally
      regenerated seedlings. It is suggested that the inhibition of photosystem II
      activity was caused by an interaction between low temperatures and light. Natural
      night frosts are proposed to increase the susceptibility to photoinhibition in
      the following day(s).

PMID- 14975815
TI  - Differences in stem respiration responses to temperature between balsam fir trees
      in thinned and unthinned stands.
AB  - The change in stem respiration rates with change of temperature was significantly
      lower in a recently thinned balsam fir (Abies balsamea (L.) Mill.) stand than in
      an unthinned stand. A comparison of respiration measurements made in the morning
      with those made in the afternoon indicated that there was more variation among
      afternoon readings and greater responses to changes in temperature among morning
      readings. Lower respiration rates in the afternoon were more common in the
      thinned stand than in the unthinned stand.

PMID- 14975816
TI  - Identification and quantitation of indole-3-acetic and abscisic acids in the
      cambial region of Quercus robur by combined gas chromatography-mass spectrometry.
AB  - A technique is described for the rapid purification of indole-3-acetic acid (IAA)
      and abscisic acid (ABA) from small quantities of the basal trunk cambial region
      tissues of 34-year-old trees of Quercus robur L. Mass spectra of IAA and ABA
      obtained from the purified extracts provide the first reported unequivocal
      identification of endogenous IAA and ABA in the cambial region of a hardwood
      species. By use of the combined gas chromatography-mass spectrometry technique of
      multiple ion monitoring, with deuterated analogs as internal standards, it was
      shown that the levels of IAA in the cambial region tissues varied from ~1 to ~20
      microg g(-1) and those of ABA from ~1 to ~5 microg g(-1) dry weight during the
      growing season. The high levels of IAA are similar to those found in the newly
      differentiating xylem tissues of softwoods.

PMID- 14975817
TI  - Identification of two compounds correlated with lack of rooting capacity of
      chestnut cuttings.
AB  - Cuttings from mature chestnut (Castanea spp.) trees are very difficult to root,
      whereas juvenile or etiolated cuttings root easily. The HPLC chromatograms from
      mature cuttings consistently showed two well-defined peaks that were absent from
      juvenile or etiolated cuttings. The compounds responsible for these two peaks
      were isolated and identified as derivatives of ellagic acid, 3,3',4-tri-O
      methylellagic acid (compound 1) and 3,4,4'-tri-O-methylellagic acid (compound
      II). Compound I significantly inhibited rooting as measured by the bean test; a
      concentration of 3.0 x 10(-5) M caused a 32% inhibition in number of roots formed
      compared with controls grown in 10(-5) M IAA. When compound I was mixed with an
      equal quantity of IAA, the rooting activity of the auxin was reduced by 31.5%. An
      insufficient amount of compound II was available for the bean assay.

PMID- 14975818
TI  - Nucleotide and nucleic acid status in shoot tips from juvenile and mature clones
      of Sequoiadendron giganteum during rest and growth phases.
AB  - Nucleoside triphosphate and nucleic acid contents of shoot tips of juvenile and
      mature clones of Sequoiadendron giganteum Buchholz were analyzed during rest and
      growth phases. In both juvenile and mature clones, shoot growth activity was
      characterized by significant increases in ATP, non-adenylic nucleoside
      triphosphate (NTP) and RNA levels. During the rest period, both ATP/NTP and
      RNA/DNA ratios were significantly higher in the juvenile clone than in the mature
      clone. However, during the growth phase, only the ATP/NTP ratio was higher in the
      juvenile than in the mature clone. The results suggest that the physiological
      differences between shoot tips of juvenile and mature tissues during the rest
      phase tend to decline as active shoot growth commences. This conclusion is
      consistent with morphological observations and with the varying organogenetic
      capacities of in vitro cultures of explants removed from stock plants at
      different times.

PMID- 14975819
TI  - In vitro meristem culture of juvenile and mature Sequoiadendron giganteum.
AB  - A total of 7000 meristems were used in experiments to investigate the possibility
      of cloning Sequoiadendron giganteum Buchholz by in vitro meristem culture of
      juvenile (2-year-old) and mature (100-year-old) ortets. Cultures were initiated
      on a low-salt medium containing 0.1 mg l(-1) 1-naphthaleneacetic acid to
      stimulate meristematic activity. Benzylamino purine (0.01-0.5 mg l(-1)) inhibited
      meristematic activity, whereas gibberellic acid (0.01-0.5 mg l(-1)) had no effect
      on meristematic development. The mature ortet showed more specific mineral
      requirements and a lower capacity for cloning than the juvenile ortet. Rooted
      plants were obtained only from the juvenile clone. There was a marked seasonal
      effect on meristematic activity, especially for the mature clone, the most active
      material being obtained during budbreak.

PMID- 14975820
TI  - In vitro plantlet formation from embryonic explants of eastern white cedar (Thuja
      occidentalis L.).
AB  - A protocol is described for the in vitro production of plantlets from embryonic
      explants of eastern white cedar (Thuja occidentalis L.). Bud induction was
      optimal when embryonic explants were cultured for 20-25 days on half-strength
      Quoirin and Le Poivre mineral salts containing equimolar concentrations (10(-6)
      M) of N(6)-benzyladenine and 2-isopentyl adenine. Bud development was achieved in
      phytohormone-free medium in the presence of activated charcoal. Maximal shoot
      elongation occurred on half-strength Quoirin and Le Poivre salts, whereas shoot
      multiplication was optimal on half-strength Bornman's MCM salts in the presence
      of cytokinin. Hardened shoots, dipped in commercial rooting powder containing
      indole-3-butyric acid, rooted optimally in mist under non-sterile greenhouse
      conditions. Both rooting and subsequent plantlet growth was best when Redi
      Earth((R)) was used as a substrate. Over 250 plantlets per embryo can be produced
      annually by this technique.

PMID- 14975821
TI  - Nitrate metabolism in Scots pine seedlings during their first growing season.
AB  - Fluctuations in nitrate reductase activity (NRA), nitrate, nitrite, protein and
      total nitrogen content of bare-root Scots pine seedlings (Pinus sylvestris L.)
      raised outdoors were investigated during the first growing season. Nitrate
      reductase activity was higher in roots than in needles, whereas NO(3) (-) content
      was higher in needles than in roots and increased in both from June to October.
      Nitrate reductase activity in roots correlated more closely with NO(3) (-) N in
      the soil than did NO(3) (-) in the roots. In autumn, there was a closer
      correlation between foliar NRA and NO(3) (-) in the needles than with NO(3) (-)-N
      in the soil. Nitrite was not detected in the seedlings during the growing season.
      Total nitrogen content decreased toward the autumn, whereas protein content
      initially decreased but increased again in autumn. Acrylic netting placed above
      the seedlings increased both air and soil temperatures and apparently accelerated
      the use of nitrate.

PMID- 14975822
TI  - Accumulation and partitioning of dry matter and mineral nutrients in developing
      kiwifruit vines.
AB  - Size, dry weight and mineral nutrient content of fruit, leaves, shoots, canes,
      leader, stem and roots of kiwifruit (Actinidia deliciosa (A. Chev.) C.F. Liang et
      A.R. Ferguson var. deliciosa) vines, aged from one to five years, were measured.
      The distribution of fruit yield among single canes was examined in three of the
      vines. Total dry weight increased from a mean of 1.29 kg vine(-1) for one-year
      old vines to 29.2 kg vine(-1) for five-year-old vines. The proportion of total
      dry weight in roots declined from the first to the third year (55 to 40%) and
      then remained approximately constant, whereas the proportion of dry weight in
      fruits increased from the first to the third year before attaining a more or less
      constant value. The proportion of total canopy dry weight contained in the
      current season's growth (fruit, leaves and shoots) averaged 75% for all ages.
      Roots of five-year-old vines had only penetrated a small proportion of the total
      soil volume available. Total fruit yield increased linearly with number of floral
      shoots for whole vines and single canes within vines, but with cane size (length
      or dry weight) for whole vines only. The productivity of single canes declined
      from 2.5 kg m(-1) for canes shorter than 0.25 m to about 1.1 kg m(-1) for canes
      longer than 1.0 m, in accordance with a declining bud density with increasing
      cane length. For vines of all ages, mineral nutrient concentrations in various
      tissues were similar, except that Ca in leaves and S in leaves and shoots
      increased with vine age. Major sites of accumulation of N, Ca, Mg, S, Fe, Mn and
      B were the leaves, whereas P and K accumulated predominantly in the fruits, Zn in
      the leader, and Na and Cu in the roots. Estimated annual mineral nutrient uptake
      increased with vine size and fruit yield, and for five-year-old vines the values
      per hectare were 141 kg N, 19 kg P, 169 kg K, 161 kg Ca, 28 kg Mg, 32 kg S, and
      less than 2 kg for Na and all micronutrients. The nutrient content of the
      harvested fruit provided an inaccurate estimate of annual nutrient uptake of the
      developing vines.

PMID- 14975823
TI  - Abscisic acid relations and the response of Populus trichocarpa stomata to leaf
      water potential.
AB  - The role of abscisic acid (ABA) in the mediation of stomatal responses to low
      leaf water potential was examined with intact plants and epidermal strips of
      Populus trichocarpa Torr. & A. Gray. Clones of this species grown under well
      watered conditions maintain a high leaf conductance when the foliage wilts.
      However, foliar ABA concentration in P. trichocarpa increased manyfold in
      response to water stress as it did also in P. deltoides Bartr. ex Marsh. and P.
      trichocarpa x deltoides hybrids. Application of ABA to epidermal strips appeared
      to cause solute leakage, however stomata of P. trichocarpa remained partially
      open even when the guard cells were plasmolyzed. Foliar application of ABA
      induced closure of stomata in young expanding leaves, but not in fully expanded
      foliage. Ten days after ABA application, stomata on young leaves were open at
      high water potential but closed at low water potential. These characteristics are
      discussed with respect to wilty mutants of tomato and potato, which also have
      stomata unresponsive to leaf wilting.

PMID- 14975824
TI  - The physiological basis for loss of rootability with age in avocado seedlings.
AB  - Rooting ability of cuttings from avocado (Persea americana Mill.) seedlings
      declined during the first 12 months of development. Cuttings from one-year-old
      seedlings rooted at a similar rate to cuttings prepared from mature plants. The
      amount of gibberellin-like substances in the leaves decreased during this time
      whereas abscisic acid content increased. Application of GA to avocado seedlings
      induced shoot elongation but failed to maintain the initial, high rooting
      ability. Treatments with ABA and AM0 1618 had no effect on either rooting or
      elongation. During the development of roots, the endogenous Avocado Rooting
      Promoter (ARP) accumulated at a faster rate in juvenile cuttings than in mature
      cuttings.

PMID- 14975825
TI  - Micropropagation of mature Calabrian pine (Pinus brutia Ten.) from fascicular
      buds.
AB  - Dormant meristems of fascicles explanted from 10-year-old, field-grown trees of
      Pinus brutia Ten. were cultured in vitro. Browning of cultured fascicles was
      reduced by including 150 mg l(-1) sodium diethyldithiocarbamate (SDD) in a
      cytokinin-containing medium. The stage of development of fascicles when placed in
      culture affected both shoot-bud production and the degree of browning. Only
      fascicles at an advanced stage of development had a high rate of shoot-bud
      production. Fascicles cultured for 6 weeks in initiation medium containing 150 mg
      l(-1) SDD and then for 4 weeks in initiation medium containing 1 mg l(-1)
      insoluble polyvinylpolypyrrolidone showed the highest rate (23%) of shoot-bud
      development and the lowest rate (15%) of browning. Elongation of activated shoot
      buds was considerably enhanced by reducing the concentration of cytokinin in the
      culture medium. Only shoots >/= 20 mm in height were capable of producing further
      crops of buds and shoots. When treated with a combination of auxin and cytokinin,
      only 16% of the elongated shoots produced roots.

PMID- 14975826
TI  - Short-term canopy interactions of beech trees: mineral ion leaching and
      absorption during rainfall.
AB  - Mineral nutrient composition of the stemflow of 70-120-year-old beech trees Fagus
      sylvatica L. in 26 stands in northwestern Switzerland was compared with that of
      incident precipitation. Four mm of precipitation was sufficient to wash-off the
      bulk of the dry deposition intercepted by the canopy. Thereafter, differences in
      composition between precipitation and stemflow provided a measure of net ion
      absorption by or leaching from the canopy. Depending on the acidity of the rain
      and on the buffering of protons by the canopy, different interactions were
      observed. Highest rates of leaching were detected for potassium whereas ammonium
      was absorbed in some stands and leached in others. Absorption of chloride was
      associated with the occurrence of H(+) buffering. The latter took place to a
      greater extent in more acidic precipitations. Interrelations of short-term canopy
      ion interactions are discussed and some implications examined.

PMID- 14975827
TI  - Comparison of the responses to flooding of seedlings and cuttings of Gmelina.
AB  - The effects of flooding on Gmelina arborea Roxb. seedlings and cuttings of the
      same parent stock were compared to determine their suitability as transplanting
      stock. Flooding caused reductions in stomatal conductance, xylem pressure
      potential and dry matter accumulation in both groups of plants. In seedlings,
      flooding induced formation of hypertrophied lenticels, stem hypertrophy and
      production of short, thick, adventitious roots in seedlings, whereas in cuttings,
      only thin roots and numerous smaller lenticels were induced. For 8 days after the
      flooding treatment ended, the flooded seedlings grew faster than control
      seedlings, whereas in cuttings, post-flooding growth was similar to that of
      control plants. It is suggested that seedlings may perform better than cuttings
      in very wet or saturated soil.

PMID- 14975828
TI  - Diurnal changes in leaf chemical constituents and (14)C partitioning in
      cottonwood.
AB  - Diurnal changes in concentrations of leaf chemical fractions and partitioning of
      photosynthetically fixed (14)C within the plant and among chemical fractions were
      studied in rapidly growing cottonwood (Populus deltoides Bartr. ex Marsh.)
      seedlings. During the light period, leaf weight (mg cm(-2)) increased by about
      25% primarily as a result of the accumulation of starch and sucrose, and to a
      lesser extent because of an increase in the content of amino acids and the
      chloroform fraction (pigments plus lipids). In contrast, reducing sugars and
      organic acids decreased in concentration. The partitioning of (14)C within the
      plant also changed during the light period. Acropetal transport to developing
      leaves and stem decreased from 81 to 55% of the total (14)C translocated from a
      source leaf in 4 hours, whereas basipetal transport to stem and roots increased
      from 13 to 37%. Although assimilation rate ((14)C fixed in 0.5 h) remained
      constant during the light period, the percentage of fixed (14)C translocated out
      of the source leaf in 4 h decreased from 27 to 9%. This change in transport rate
      of recently fixed (14)C was caused by a shift in (14)C partitioning from
      transport sucrose to storage starch. During the light period, the incorporation
      ratio ((14)C-sugar/(14)C-starch) decreased from 40 at 0700 h to 2 at 1900 h. The
      partitioning of carbon to different chemical fractions within the source leaf and
      the interactions or feedback between different sinks and the source leaf have a
      major influence on plant growth and development. Control of this carbon
      partitioning is located in both source and sink leaves.

PMID- 14975829
TI  - Indole 3-acetic acid concentration in the leading shoot and living stem bark of
      Scots pine: seasonal variation and effects of pruning.
AB  - Seasonal changes in the concentration of indole-3-acetic acid (IAA) in the
      leading shoot and in the live tissue external to the xylem (living bark) of 2-3 m
      tall Scots pine (Pinus sylvestris L.) trees were observed over a period of three
      years. Both the leading shoot and the living bark showed a consistent pattern of
      seasonal variation in IAA content, with maxima of about 150 and 350 ng g(-1)
      (fresh weight), respectively. The IAA concentration in both tissues increased in
      late June at the time of shoot growth termination, decreased from late August,
      and by October reached a low value, which was maintained throughout the winter.
      Excision of current year shoots on the upper branches decreased the annual stem
      diameter increment without affecting the concentration of IAA in the living bark.
      However, excising the leading shoot, or girdling the mainstem beneath the leading
      shoot, caused a substantial reduction in the IAA content of the living stem bark.

PMID- 14975830
TI  - Dynamics of indole-3-acetic acid during germination of Picea abies seeds.
AB  - High performance liquid chromatography and combined gas chromatography-mass
      spectrometry were used to identify indole-3-acetic acid (IAA) and indole-3
      ethanol as endogenous constituents of germinating Norway spruce (Picea abies (L.)
      Karst.) seeds. Indole-3-methanol was tentatively identified by multiple ion
      monitoring. The free IAA content of the seeds rose from about 20 ng g(-1) to
      about 60 ng g(-1) (dry weight) during the first five days of germination and
      thereafter declined to around 20 ng g(-1). Indole-3-acetic acid released by
      alkaline hydrolysis, which was initially present at about 110 ng g(-1), decreased
      to 5-10 ng g(-1) during the first week of germination. The IAA content of seed
      lots differing in germination behavior was investigated. The findings are
      discussed in relation to the metabolism of IAA in conifer seeds.

PMID- 14975831
TI  - Pollution-induced injury in North American forests: facts and suspicions.
AB  - Toxic gases are the only airborne chemicals that have been demonstrated to cause
      detrimental effects on forest trees in North America. Ozone is the only
      regionally dispersed pollutant known to have injured foliage, decreased radial
      growth, decreased resistance to insects and diseases, and increased mortality of
      sensitive tree species over a wide geographic range. All of these effects have
      been observed in eastern white pine (Pinus strobus L.) throughout its natural
      range, in some conifers and hardwood trees in southern California, and in a few
      tree species in the central Appalachian Mountains. Very little research has been
      done to determine effects of airborne chemicals on forests as a whole. At
      present, there is no conclusive evidence that acid deposition or other regionally
      dispersed pollutants are affecting the productivity of any forest in North
      America.

PMID- 14975832
TI  - Stand dynamics and the evaluation of forest decline.
AB  - The importance of understanding effects of stand dynamics on growth as they
      relate to identifying and evaluating forest declines is discussed. Decline
      diseases and some of their characteristics are reviewed, as are general patterns
      of normal growth and development of forest trees and stands. The need to develop
      an expectation of normal growth is discussed and a minimally sufficient set of
      growth stratifying factors; namely, site quality, stand density and age, is
      proposed.

PMID- 14975833
TI  - Forest decline: modeling the effect of climate in tree rings.
AB  - Tree rings provide an historical record of forest growth that reflects changes
      with time in site factors including, competition, tree and stand age, fire and
      other disturbances, and climate. Statistical methods can be used to factor out
      climatic influences on radial growth to yield a climate response model that can
      indicate whether declines in forest productivity are related to the modeled
      climatic variables or to other influences such as atmospheric pollutants. A
      general method, based on ordinary least squares, is presented for creating
      climatic response models for forest decline studies. The crux of the method is
      model verification, whereby the time-stability of the model is tested before it
      is used to forecast tree-ring variations during a period of decline. Three
      studies are described that employ monthly mean temperatures to predict tree-ring
      indices in declining red spruce (Picea rubens Sarg.) stands in the Appalachian
      Mountains of North America. The results indicate that, since 1960, red spruce
      trees at most of the sites sampled have undergone a period of growth decline that
      is unrelated to changes in mean monthly temperature. However, an association
      between annual ring width and unusual departures from the mean summer and winter
      temperatures during both present and past periods of decline suggests that
      climatic effects are implicated to some degree in the current decline.

PMID- 14975834
TI  - Physiology and genetics of tree growth response to moisture and temperature
      stress: an examination of the characteristics of loblolly pine (Pinus taeda L.).
AB  - Water stress and temperature impose fundamental limits to forest productivity.
      Stresses caused by fluctuating or extreme temperatures or limited water
      availability vary both seasonally and from year to year. The role of these
      stresses should be considered when investigating the causes of declines in forest
      productivity. Forest growth, or carbon gain, can be related quantitatively to
      three components: leaf area, rate of net photosynthesis and rate of respiration.
      This paper examines effects of temperature and water supply on these components
      with particular reference to loblolly pine (Pinus taeda L.), a species of
      economic importance in the southeastern United States where declines, of unknown
      cause, in forest productivity have been reported.

PMID- 14975835
TI  - Quantifying plant response to ozone: a unifying theory.
AB  - Published information about the effects of ozone on plants and ecosystems is
      synthesized into a conceptual model to explain the response of evergreen
      conifers, deciduous hardwoods and agricultural crops to ambient levels of ozone
      pollution. The effects of ozone on carbon balance and growth of individual plants
      can be quantified on the basis of concentration, external dose (concentration x
      duration of exposure), or uptake. For an equivalent dose within a single growing
      season, agricultural crops are the most sensitive to ozone, with hardwoods
      intermediate and conifers least sensitive. In contrast, all species display a
      similar decline in photosynthesis and growth in response to equivalent total
      uptake or uptake per leaf life span, with trees somewhat less sensitive than
      agricultural crops on a calendar time scale, but slightly more sensitive on a
      relative (leaf life span) time scale. Among species, differences in ozone uptake
      and response can be predicted from differences in the inherent leaf diffusive
      conductance.

PMID- 14975836
TI  - Interactions of insects, trees and air pollutants.
AB  - Hypotheses of forest decline are summarized. Stressed trees may be a more
      suitable food source for invertebrate herbivores than unstressed trees because
      stress causes an increase in the tissue content of soluble nitrogenous compounds.
      There is reasonable correlative evidence that air pollutants influence the
      outbreak patterns of forest insect species. In some cases, formerly innocuous
      insects may become pests. The occurrence of specific insect pests with specific
      air contaminants is reviewed. Emphasis is placed on the decline of Fraser fir
      (Abies fraseri (Pursh) Poir.) in the southern Appalachians and the occurrence of
      the balsam woolly adelgid. Variable mortality patterns of Fraser fir may be
      caused by locally distributed air pollutants acting in combination with other
      types of stress including that caused by the adelgid.

PMID- 14975837
TI  - The role of physiology in forestry.
AB  - Although a great deal of information concerning the physiology of trees has been
      accumulated, physiology has made a smaller contribution to forestry than it
      should. This is partly because of a lack of communication between field and
      laboratory workers and partly because of a lack of a general understanding of the
      role of physiology in forestry. The physiological processes of trees are the
      machinery through which the genetic potential and the environment operate to
      determine the quantity and quality of growth. Actual wood production usually is
      far below the genetic and physiological potential because important physiological
      processes are often inhibited by environmental stresses such as drought, mineral
      deficiencies, unfavorable temperatures, and air pollution. The most useful
      contribution that physiologists can make to forestry is to determine which
      physiological processes are inhibited by particular stresses and suggest to tree
      breeders what characteristics will minimize the inhibitory effects of these
      stresses. Cooperative screening studies with geneticists to identify differences
      among families and provenances that result in differences in stress tolerance
      should be very productive. Perhaps as the cost of establishing forest stands
      increases, more attention will be paid to the selection of genotypes with
      physiological characteristics best suited to local environments. Because of the
      complex interactions among stresses there is need for long-term interdisciplinary
      research programs in which soil scientists, meteorologists, and physiologists
      cooperate with foresters and forest geneticists in identifying stresses and their
      inhibitory effects on forest productivity. Because of the increasing
      specialization in science there also is great need for broadly trained
      generalists who can understand research in several fields, identify important
      contributions, and show their significance to investigators in other fields.

PMID- 14975838
TI  - Site fertility affects seasonal carbon reserves in loblolly pine.
AB  - Concentrations of nitrogen, phosphorus and total non-structural carbohydrates
      were examined in loblolly pine foliage from control stands and stands fertilized
      with sludge containing 450 kg N ha(-1). Needles from the fertilized sites had
      higher N concentrations regardless of needle age. Fertilization increased P
      concentration in needles relative to the control sites. Seasonal patterns of
      change in sugar concentrations were similar among sites for both current-year and
      one-year-old needles, the highest concentration (126 mg g(-1)) occurring in
      February. Sugar concentrations were lowest in June and were generally lower in
      current needles than year-old needles. Starch concentrations and the amount of
      starch per fascicle varied both seasonally and among sites. Fertilization
      increased starch reserves in current needles at the end of the growing season (7
      mg g(-1) and 14 mg g(-1) for the control and fertilized sites, respectively), and
      increased the rate of starch mobilization during the initiation of needle growth.
      In the growing season, starch concentrations were lower in current foliage from
      high fertility sites than low fertility sites. Carbon reserves accumulated during
      the growing season in mature one-year-old needles from control sites indicating a
      lower sink strength for carbon under low nutrient conditions. There was a
      positive relationship between starch and nitrogen concentrations during the
      dormant season whereas the relationship was negative during the growing season.
      The magnitude and direction of change in starch reserves with the onset of growth
      following the dormant season may indicate nutrient limitation and potential
      growth response to fertilization.

PMID- 14975839
TI  - A comparison of rates of aboveground growth and carbon dioxide assimilation by
      aspen on sites of high and low quality.
AB  - Net assimilation rates of 10-year-old naturally regenerated bigtooth aspen
      (Populus grandidentata Michx.) at two sites in northern Michigan, USA, were
      compared to test the hypothesis that site-related differences in aboveground
      production depends solely on differences in rates of CO(2) assimilation. On a
      leaf weight basis, aboveground production on the better site was over twice that
      on the poorer site, whereas maximum CO(2) assimilation rates on the better site
      were only 48% higher, leading to a rejection of the hypothesis. Soil respiration
      rates on the two sites were comparable, suggesting that the difference between
      sites in aboveground production can be attributed in part to a difference in the
      proportion of total assimilate allocated belowground.

PMID- 14975840
TI  - Accumulation of starch in roots and foliage of loblolly pine (Pinus taeda L.):
      effects of season, site and fertilization.
AB  - Accurate predictions of stand response to nitrogen fertilization require a better
      understanding of the plant processes associated with stand nutrition. This study
      examined the relationship between stand nutrition and starch accumulation in
      roots and foliage of loblolly pine (Pinus taeda L.). A field study was located on
      the lower Coastal Plain of North Carolina on four sites of differing soil types.
      Stands of 8-year-old trees were fertilized with nitrogen (225 kg ha(-1)) or
      nitrogen plus phosphorus (225 kg N ha(-1) + 75 kg P ha(-1)) in 1981. Roots and
      foliage were collected from five trees per plot at six sampling dates from July
      1983 through January 1985 and analyzed for starch. Starch concentrations showed
      seasonal fluctuations, with levels generally highest in early spring prior to
      budbreak. Root starch concentrations were lowest in autumn, whereas foliar
      concentrations were lowest in winter.

PMID- 14975841
TI  - Physiographic, stand, and environmental effects on individual tree growth and
      growth efficiency in subalpine forests.
AB  - Annual volume growth of subalpine trees in the central Rocky Mountains was
      studied in relation to site and stand conditions. Growth of individual trees was
      most strongly influenced by estimated potential absorbed radiation, which varied
      with physiographic conditions and tree leaf area. Growth efficiency was estimated
      by the ratio of annual volume growth to potential radiation absorption by the
      crown. Growth efficiency was higher in young lodgepole pine (Pinus contorta var.
      latifolia Engelm.) than in Engelmann spruce (Picea engelmannii Parry ex Engelm.)
      or subalpine fir (Abies lasiocarpa (Hook.) Nutt.). In all species, growth
      efficiency declined sharply with age, and suppressed and overtopped trees had
      growth efficiencies equal to the highest efficiencies observed for
      dominant/codominant or intermediate trees. Lodgepole pine growth was most
      responsive to site and stand variables, Engelmann spruce was intermediate, and
      subalpine fir was rather unresponsive.

PMID- 14975842
TI  - Uptake of carbon and nitrogen at decreased nutrient availability in small birch
      (Betula pendula Roth.) plants.
AB  - Uptake of carbon and nitrogen in relation to mineral nutrient supply was
      investigated in small birch (Betula pendula Roth.) plants grown in solution
      culture. A step-decrease in nutrient availability (from near-optimal to a low
      rate of supply) caused an immediate and temporary cessation in net uptake of
      nitrogen to leaves and a sharp reduction in rate of leaf expansion. Both net
      uptake of nitrogen to leaves and leaf area expansion subsequently resumed but at
      a rate matching the decreased nutrient supply. Whole plant- and root-relative
      growth rates also decreased with mineral nutrient supply, although root growth
      rate decreased more slowly than that of the whole plant, resulting in an
      increased fraction of plant dry matter in the roots. During the lag phase, net
      shoot photosynthesis exceeded carbon use in structural growth and respiration as
      indicated by high starch concentrations in the whole plant. Over a wide range of
      mineral nutrient availabilities, the stable ratios of leaf area and plant growth
      rate to plant nitrogen content remained unchanged. Starch concentrations were
      higher at the lower nutrient availabilities, suggesting that carbon uptake was
      not regulated solely by the rate of carbon use in structural growth and
      respiration. It was calculated that net photosynthetic and transpiration rates
      were such that the intercellular-CO(2) concentration of leaves was largely
      independent of plant nutrient supply.

PMID- 14975843
TI  - Relationships between nutrient status, carbon assimilation and water use
      efficiency in Pinus radiata (D. Don) needles.
AB  - The productivity of Pinus radiata D. Don plantations can be increased on many
      soils by N and P fertilization. Foliar analyses are usually taken as a guide for
      nutrient management, but there is little information about the relationship of
      foliar nutrient status to foliar physiology. This paper provides such information
      from N and P fertilization experiments. The concentrations and contents of N and
      P in the needles of P. radiata change because of accumulation during needle
      growth, retranslocation during shoot growth, and replenishment from current
      uptake during periods of little shoot growth. Up to 60% P and 50% N may be
      retranslocated in a single growing season from needles less than one year old.
      Three years after fertilizer application to a 10-year-old thinned P. radiata
      stand, net carbon assimilation rate per unit leaf area was in the order NP>P>N.
      There were positive associations between foliar P and assimilation at full
      sunlight, diffusive conductance and quantum yield. Foliar N was negatively
      associated with these variables. Higher concentrations of P and N were both
      accompanied by higher instantaneous water use efficiency by the foliage.
      Estimated trends in whole tree assimilation were similar to those in aboveground
      biomass accumulation. The interplay between the dynamic nature of nutrients in
      the foliage and their influence on the physiology of needles is discussed.

PMID- 14975844
TI  - Stomatal responses to humidity in selected conifers.
AB  - Stomatal response to changes in leaf-to-air water vapor pressure difference (D)
      was studied in needles of the current year's shoot of three-year-old seedlings of
      Picea sitchensis (Bong.) Carr., Pinus contorta Dougl. ex Loud., Larix x eurolepis
      Henry, and Pinus sylvestris L. Both eight-week- and ten-month-old shoots of P.
      sylvestris were studied. Stomata of all the species responded by closing to some
      degree as D was increased over the range 0.4-2.0 kPa. Ten-month-old shoots of P.
      sylvestris showed the smallest reduction (7.5%), and shoots of P. sitchensis the
      largest reduction (64.6%) in stomatal conductance. However, in no species was
      stomatal closure sufficient to cause a reduction in transpiration (E) as D
      increased. Net photosynthesis (A) declined linearly as D was increased and as a
      result the ratio of E/A increased linearly in all species. Only the stomata of P.
      contorta and L. x eurolepis behaved in an 'optimal' way, i.e., estimated values
      of dEdA were approximately constant as D increased. For P. sylvestris, shoots of
      both ages, dE/dA increased markedly with D, whereas in P. sitchensis it declined.
      Explanation of these data does not require a mechanism of stomatal closure
      involving a site that senses the vapor pressure deficit outside the leaf.
      However, it is unlikely that a simple 'feedback' response involving bulk leaf
      water potential can explain the responses measured because changes in needle
      water potential were less than 0.1 MPa during an experiment.

PMID- 14975845
TI  - Transpiration of a 31-year-old Chamaecyparis obtusa Endl. stand before and after
      thinning.
AB  - Daily transpiration before and after thinning was measured on six individual
      trees in a 31-year-old Chamaecyparis obtusa Endl. stand by the heat pulse method.
      After thinning, daily transpiration of a tree at a given level of solar radiation
      increased, and the difference between before and after thinning increased with
      solar radiation. The increase after thinning was related to a high rate of crown
      transpiration caused by greater canopy exposure and, subsequently, to the
      increase in foliage biomass per tree. Stand transpiration was calculated on the
      basis of two parameters, daily solar radiation and daily maximum vapor saturation
      deficit of the air. During the growing season (April to September), transpiration
      of a tree increased following thinning whereas transpiration of the stand
      decreased 21% after thinning. This decrease was associated with a 24% decrease in
      leaf mass of the stand following thinning.

PMID- 14975846
TI  - The influence of NaCl on leaf water relations and the proportions of K, Na, Ca,
      Mg, and Cl in epidermal cells of Fraxinus excelsior L.
AB  - The influence of NaCl on leaf water relations was investigated in 3-4-year-old,
      potted Fraxinus excelsior L. trees. Until midsummer, the application of NaCl to
      the soil resulted in increased leaf water potentials (Psi) and stomatal diffusive
      resistances (r(s)). The improved water status seems to be due to a latent injury
      rather than to an adaptive response of the plant because, despite the initial
      increases in Psi and r(s), leaf necrosis developed in midsummer. Altered
      hydraulic resistances were detected at the time the leaves became necrotic. X-ray
      analysis of frozen, hydrated leaf tissue from NaCl-treated trees showed
      substantial increases in Ca(2+) and Mg(2+) content in the epidermal cells. These
      changes in elemental composition of the leaves from NaCl-treated plants may be
      associated with malfunction of the stomatal apparatus.

PMID- 14975847
TI  - Stomatal resistance, photosynthesis and water relations in mountain birch in the
      subarctic.
AB  - The role of water in regulating stomatal aperture and carbon assimilation of
      mountain birch (Betula pubescens Ehrh. ssp. tortuosa (Ledeb.) Nyman) was studied
      in the Swedish Subarctic. Stomata exhibited a clear response to changes in
      humidity and water potential. High evaporative demand caused stomatal closure at
      midday. The diurnal curve of net photosynthesis, measured on a warm day in early
      July, had two peaks, and photosynthetic rate was reduced by 25-30% at midday.

PMID- 14975848
TI  - Stomatal and nonstomatal limitations to net photosynthesis in Pinus taeda L.
      under different environmental conditions.
AB  - Net photosynthesis, transpiration and stomatal conductance of two-year-old Pinus
      taeda L. seedlings were compared under various environmental conditions.
      Responses to air temperature, irradiance, ambient CO(2) concentration, absolute
      humidity deficit and xylem pressure potential were examined. The seedlings
      exhibited little response to a wide range of absolute humidity deficits (7 to 16
      g m(-3)) and temperatures (20 to 35 degrees C), but were sensitive to changes in
      water deficit, irradiance and CO(2) concentration. Net photosynthesis and
      stomatal conductance were linearly related under all of the environmental
      conditions measured. However, the gas phase limitation to photosynthesis was
      generally small (20 to 30%). It was concluded that although the stomatal response
      was closely coupled to changes in photosynthesis, internal limitations, rather
      than the rate of gaseous diffusion of CO(2), were primarily responsible for
      limiting photosynthesis.

PMID- 14975849
TI  - Effect of low root temperature on net photosynthesis, stomatal conductance and
      carbohydrate concentration in Engelmann spruce (Picea engelmannii Parry ex
      Engelm.) seedlings.
AB  - The effect of low root temperature on net photosynthesis, stomatal conductance
      and carbohydrate concentration in potted Engelmann spruce (Picea engelmannii
      Parry ex Engelm.) seedlings was examined under controlled growth-chamber
      conditions. Root temperature had no effect on net photosynthesis between 10 and
      20 degrees C, however, conductance and photosynthesis declined sharply below 8
      degrees C. Net photosynthesis and stomatal conductance decreased to 50 and 34% of
      the initial values after 7 days at a root temperature of 0.7 degrees C. Low root
      temperature also caused a decrease in photosynthetic utilization of internal
      CO(2), carboxylation efficiency and apparent quantum yield, and it was concluded
      that the decrease in photosynthetic rate was caused primarily by nonstomatal
      limitations. Root chilling caused a small increase in starch content in needles
      and stems and induced the hydrolysis of starch to glucose in roots. The increase
      in glucose concentration may enable continued root growth at low temperatures.

PMID- 14975850
TI  - On estimating canopy photosynthesis and stomatal conductance in a deciduous
      forest with clumped foliage.
AB  - The foliage in a fully-leafed deciduous forest canopy is clumped. Consequently,
      theory indicates that the probability of beam penetration will be estimated more
      accurately with a model based on the negative binomial distribution than with a
      model based on the Poisson distribution, incorporating an assumption of a
      spherical leaf inclination angle distribution. Flux densities of
      photosynthetically active radiation (PAR) were measured in and above a deciduous
      forest canopy and were computed with the canopy radiative transfer models based
      on the negative binomial and Poisson distributions. These radiation values were
      used to compute canopy photosynthesis and stomatal conductance. Canopy
      photosynthesis and stomatal conductance, based on the negative binomial model,
      overestimated values computed from measured PAR profiles by 8 and 9%.
      respectively. The canopy photosynthesis and stomatal conductance values computed
      with the spherical Poisson model under-estimated measured values by 17 and 10%,
      respectively. Thus, the negative binomial radiative transfer model improves
      estimates of canopy photosynthesis and, to a lesser extent, stomatal conductance,
      inside a deciduous forest.

PMID- 14975851
TI  - Optimal control of gas exchange.
AB  - A major difficulty in evaluating the optimization theory of leaf gas exchange
      under conditions of water deficit has been that of obtaining suitable
      experimental data. Mathematical solutions to three formulations of optimal
      stomatal control are presented which can be tested experimentally. First, it is
      assumed that the movement of stomata and changes in environmental factors are
      slow compared to changes in the internal CO(2) concentration. The optimization
      problem is solved under this assumption, and the procedures for testing the
      solution experimentally are described. Second, instantaneous stomatal response is
      postulated and the solution suggests that very rapid oscillations provide optimal
      CO(2) uptake. Third, variable stomatal dynamics are postulated and the
      mathematical solution shown to be similar to that of the second case. The second
      and third cases can also be tested empirically.

PMID- 14975852
TI  - Carbon, water and nitrogen relations in evergreen and deciduous conifers.
AB  - Comparisons of carbon, water and nitrogen relations in 33-year-old trees were
      made among evergreen spruce (Picea abies L.) and three deciduous larch species
      (Larix decidua Mill., L. leptolepis Gord. and their hybrid L. dec. x lep.), in a
      field experiment near Bayreuth (West Germany). Nitrogen content per unit dry
      weight was higher in larch needles than in spruce needles as was the
      photosynthetic capacity per unit of needle dry weight and area. Area related
      water demand of the deciduous needles was higher at the needle and crown level
      than in spruce, whereas evergreen spruce needles displayed a higher water use
      efficiency. However, because of foliage longevity and thus lower carbon
      investment in current-year foliage, spruce trees achieved the same stem increment
      as larch trees of similar age and height. A simulation illustrates that evergreen
      trees are able to achieve annual carbon gains comparable to deciduous trees
      because deciduous trees have a higher water demand and nitrogen investment in the
      current-year needles compared with evergreen trees that depend on longevity of
      functioning needles.

PMID- 14975853
TI  - Changes in carbon allocation patterns in spruce and pine trees following
      irrigation and fertilization.
AB  - The paper presents an overview of the results of long-term fertilization and
      irrigation experiments in stands of Scots pine (Pinus sylvestris L.) and Norway
      spruce (Picea abies (L.) Karst.). Large increases in stemwood production during
      the first 12 years of the experiments were achieved by fertilization especially
      when a balanced mixture of macro- and micronutrients was applied. The effect of
      irrigation alone was small, but it greatly enhanced the response of the ground
      vegetation to the application of a balanced fertilizer. Fertilization did not
      greatly affect the leaf/stemwood biomass ratio, but reduced the ratio of fine
      roots to total biomass. Drought reduced the coarse-root biomass/fine-root biomass
      ratio.

PMID- 14975854
TI  - Simulation model of a laboratory-grown phreatophytic woody legume.
AB  - A mechanistic model was developed to simulate growth of mesquite Prosopis
      glandulosa Torr. trees under a phreatic (groundwater) moisture regime.
      Experimental data obtained in a greenhouse reproducing the phreatic environment
      (2 m soil columns with 10 cm of water-saturated soil at the bottom) were used to
      parameterize three submodels predicting carbon (C), nitrogen (N) and water
      dynamics in leaves, branches, roots and root nodules. In the column simulation
      model (COLSIM), photosynthesis was driven by air temperature and soil salinity.
      Water availability was nonlimiting. Nitrogen was absorbed by the roots from
      inorganic soil N and also fixed by root nodules. Comparison of the simulation
      with results from the greenhouse experiment showed that the model accurately
      reproduced shoot biomass and nitrogen content dynamics up to three years with or
      without a high soil salinity content. Root biomass was underestimated when soil
      salinity was high because the model did not account for the increased allocation
      of C to roots under conditions of high salinity. Observed annual cycles of water
      uptake during the three-year run were not reproduced because the model did not
      include a phenological function which apparently drives these cycles.

PMID- 14975855
TI  - A conceptual model for primary productivity, decomposition and nitrogen cycling
      in the Chihuahuan creosotebush desert.
AB  - The conceptual framework for a simulation model of primary productivity,
      decomposition and nitrogen cycling in a shrub-dominated desert ecosystem in
      southern New Mexico is presented. This model is based on our previous attempt to
      simulate carbon allocation patterns in the desert shrub Larrea tridentata Cov.,
      which demonstrated that moisture patterns alone are insufficient to predict
      desert productivity. These results, as well as others, suggest that mineral
      nutrients, especially nitrogen, may also be an important determinant of
      productivity in arid environments. Our current research in the Chihuahuan desert
      is directed towards elucidating the numerous biotic and abiotic interactions that
      determine the rates and directions of carbon, nitrogen and water fluxes in this
      ecosystem. The development of this working model will serve as a tool to
      accomplish three major objectives: (1) to synthesize the large amount of existing
      data on decomposition and nitrogen cycling in deserts, (2) to quantify our
      present state of knowledge about the structure and function of ecosystem
      components important in carbon and nitrogen dynamics in deserts, and (3) to
      address hypotheses concerning the complex mechanisms of interactions and
      feedbacks among the organisms involved in carbon and nitrogen exchanges in
      deserts.

PMID- 14975856
TI  - Effects of carbon dioxide enrichment and nitrogen supply on growth of boreal tree
      seedlings.
AB  - The effects of two levels of atmospheric carbon dioxide (350 microl l(-1), 750
      microl l(-1)) and three levels of nitrogen (15.5 mM, 1.55 mM, 0.155 mM N) on
      biomass accumulation and partitioning were examined in aspen (Populus tremuloides
      Michx.) and white spruce (Picea glauca (Moench) Voss) seedlings grown in
      controlled environment rooms for 100 days after germination. Nitrogen supply had
      pronounced effects on biomass accumulation, height, and leaf area of both
      species. Root weight ratio (RWR) of white spruce was significantly increased at
      the lowest level of nitrogen, whereas RWR of aspen did not change much with
      increasing levels of nitrogen. Carbon dioxide enrichment significantly increased
      (1) the leaf and total biomass of spruce seedlings grown in the high-N regime,
      (2) the RWR of seedlings in the medium-N regime, and (3) the root biomass of
      seedlings in the low-N regime after 100 days. Carbon dioxide enrichment of aspen
      temporarily increased biomass and height in all three nitrogen regimes. Root,
      stem, and leaf mass, height, and leaf area of aspen were increased only at the 30
      day harvest in the high-N treatment and at 50 and 60 days in the low-N treatment.
      Height, stem biomass, and leaf biomass of aspen seedlings were significantly
      increased by CO(2) enrichment after 40 days in the medium-N treatment. These
      effects did not persist, possibly because of the onset of mineral nutrient supply
      limitations with increasing plant size.

PMID- 14975857
TI  - Carbon-nitrogen interactions in CO(2)-enriched white oak: physiological and long
      term perspectives.
AB  - The responses of forest trees to atmospheric CO(2) enrichment will depend in part
      on carbon-nutrient linkages. Insights into the possible long-term ecological
      consequences of CO(2) enrichment can be gained from studying physiological
      responses in short-term experiments. One-year-old white oak (Quercus alba L.)
      seedlings were grown in unfertilized forest soil for 40 weeks in controlled
      environment chambers with ambient (362 microl l(-1)) or elevated (690 microl l(
      1)) CO(2). As previously reported, seedling dry weight was 85% greater in the
      elevated CO(2) environment, despite severe nitrogen deficiency in all seedlings.
      The increase in growth occurred without a concomitant increase in nitrogen
      uptake, indicating an increase in nitrogen-use efficiency in elevated CO(2). The
      weight of new buds was greater in elevated CO(2), suggesting that shoot growth in
      the next year would have been enhanced relative to that of seedlings in ambient
      CO(2). However, there was less translocatable nitrogen in perennial woody tissue
      in elevated CO(2); thus, further increases in nitrogen-use efficiency may not be
      possible. The leaves that abscised from seedlings in elevated CO(2) contained
      higher amounts of soluble sugars and tannin and a lower amount of lignin compared
      with amounts in abscised leaves in ambient CO(2). Based on lignin:N and lignin:P
      ratios, the rates of litter decomposition might not be greatly affected by CO()
      enrichment, but the total amount of nitrogen returned to soil would be lower in
      elevated CO(2).

PMID- 14975858
TI  - Growth and physiological responses of Pinus ponderosa Dougl ex P. Laws. to long
      term elevated CO(2) concentrations.
AB  - Seven-year-old ponderosa pine (Pinus ponderosa Dougl. ex P. Laws.) saplings and
      one- and two-year-old ponderosa pine seedlings of a Sierra Nevada and a Rocky
      Mountain seed source, respectively, were exposed to CO(2)-enriched atmospheres in
      an outdoor open-top chamber facility for 2.5 years. Seedling growth (main stem
      diameter, height, volume) increased with increasing CO(2) concentration, though
      the two populations exhibited different patterns of response. By the beginning of
      the last growth season, however, the trees under the highest CO(2) concentrations
      showed signs of stress that included accelerated needle abscision, chlorosis, and
      apparent alteration of tolerance to heat. The stress response is at least partly
      attributable to elevated foliar temperatures resulting from CO(2)-induced
      stomatal closure, which in turn lowered transpirational cooling of needles.

PMID- 14975859
TI  - High technology biomass production by Salix clones on a sandy soil in southern
      Sweden.
AB  - An investigation was undertaken to (1) determine maximum biomass production of
      fast-growing Salix clones on dry or nutrient-deficient land where adequate
      nutrients and water are supplied by irrigation and fertilization, (2) compare the
      efficiency of different irrigation-fertilization systems, (3) investigate the
      possibilities of successively increasing soil fertility by a fertilization
      routine adjusted to growth and uptake, (4) monitor the leakage of different
      nutrients to groundwater, and (5) make economic calculations with respect to the
      different irrigation-fertilization systems. The experimental area, which was
      abandoned farmland, was planted in 1982 with clones of Salix. The soil was very
      sandy with small amounts of organic matter. The groundwater table was 2-3 m deep.
      The pH of the soil at 0-15 cm depth was initially 4.8-5.5. Three irrigation
      fertilization systems were used: (1) drip, (2) sprinklers, and (3) subsurface
      irrigation. During summer 1984, the area was irrigated and fertilized once a week
      for 12 weeks with a complete liquid fertilizer equivalent to 10 kg N per week.
      Production was about 1 kg m(-2) and 3 kg m(-2) for 1- and 2-year-old shoots,
      respectively. There were no significant differences between the irrigation
      fertilization systems or between the species and clones, for either 1- or 2-year
      old shoots.

PMID- 14975860
TI  - A morphological index of Quercus seedling ontogeny for use in studies of
      physiology and growth.
AB  - Attempts to relate plant metabolic activity with developmental stage are often
      hindered by lack of an appropriate developmental index. Existing indices of
      morphological development are unsuitable for use with plants having a
      semideterminate, recurrently flushing pattern of growth as displayed by Quercus
      seedlings. We propose the following morphological index (QMI) to define the
      stages of Quercus seedling ontogeny: (1) radicle emergence; (2) epicotyl
      emergence from the soil; and (for each flush) (3) termination of elongation of
      the second internode, which corresponds with the period of most rapid stem
      elongation; (4) completion of elongation by all internodes, which corresponds
      with the period of most rapid leaf elongation; and (5) completion of elongation
      of the last leaf but one, which usually precedes closely the pause between one
      growth flush and another. The relationship between QMI and net photosynthesis by
      individual leaves of Quercus rubra L. seedlings was determined. Net
      photosynthesis increased with QMI during a flush, but at a particular QMI stage,
      generally decreased from one flush to the next.

PMID- 14975861
TI  - Dimensions of the growing shoot and the absolute growth rate of a poplar shoot.
AB  - Plants of Populus euramericana (Dode) Guinier Robusta were grown in sub
      irrigated, gravel-filled containers under conditions of constant temperature and
      irradiance. Lengths of leaves and internodes and diameters of internodes were
      measured three times a week. Dates of internode maturation were estimated from
      the growth curves of the internodes. At these dates, the length of the elongating
      portion of the shoot, or growing shoot (GS), could be determined. The growing
      shoot increased in length as a function of plant age. The diameter of GS was
      related to its length. The relationship between the volume of GS and both the
      absolute growth rate of a branch and the architecture of the vascular system are
      discussed.

PMID- 14975862
TI  - Leaf development and leaf stress: increased susceptibility associated with sink
      source transition.
AB  - Relationships between leaf age and leaf susceptibility to biotic and abiotic
      stress agents have been studied, but unifying concepts relating leaf ontogeny to
      stress susceptibility are not well developed. Leaves go through predictable and
      orderly physiological stages as they progress from metabolite sinks to metabolite
      sources and then become senescent. During this process, they may pass through a
      stage of maximum susceptibility to a given stress. It is proposed that, for many
      leaf stresses, this stage occurs at the time of the sink-source transition and
      can be related to anatomical, physiological and biochemical leaf ontogeny. This
      concept may be useful in relating host-plant growth habit and leaf production
      pattern to the distribution and abundance of herbivores and leaf pathogens.

PMID- 14975863
TI  - Evidence of competition for photosynthates between growth processes and oleoresin
      synthesis in Pinus taeda L.
AB  - A group of 10 pines (Pinus taeda L.) in a 35-year-old stand in Central Louisiana
      was sampled periodically from March through December 1984 for oleoresin flow from
      small wounds. Oleoresin yield was closely associated with periods of calculated
      moderate soil water deficit and presumed growth reduction. The period of maximum
      oleoresin flow coincided with the period of calculated maximum soil water
      depletion. Calculated potential evapotranspiration reached a maximum in late
      June, but water deficits did not reach maximum levels until September.
      Apparently, moderate seasonal water deficits that limit growth, but do not limit
      photosynthesis and translocation of photosynthates, favor differentiation
      processes, such as oleoresin synthesis. Because oleoresin is a primary defense
      against southern pine beetle (Dendroctonus frontalis Zimm.) attack in pines,
      recognition of these relationships should contribute to an understanding of
      southern pine beetle-host tree interactions.

PMID- 14975864
TI  - Effects of aluminum on growth, development, and nutrient composition of
      honeylocust (Gleditsia triacanthos L.) seedlings.
AB  - Hydroponic experiments were conducted to determine the effects of aluminum (Al)
      on root development, shoot morphology and the nutrient composition of honeylocust
      seedlings (Gleditsia triacanthos L.). Seedlings were grown at pH 4 in a nutrient
      solution containing 0, 50, 150, 600 or 1500 microM Al. Within seven days, there
      were significant differences in root growth and root nutrient composition between
      control seedlings and seedlings grown in the presence of 150 or 600 microM Al. By
      day 14, significant reductions in leaf production and plant height were observed
      in seedlings treated with 1500 microM Al. At the lowest Al concentration, 50
      microM, leaf size and expansion rates were significantly lower than in the
      controls. By the third week of the experiment, Ca and Mg concentrations in young
      leaves of the Al-treated seedlings were significantly lower than in leaves of
      control plants. Analysis of old leaf tissue, however, revealed no consistent
      pattern of nutrient concentration with Al treatment.

PMID- 14975865
TI  - Alkaline runoff, soil pH and white oak manganese deficiency.
AB  - Rainfall, surface runoff, and root zone pH values were determined in an effort to
      explain symptoms of decline in white oaks (Quercus alba L.) growing in, and
      downslope from, a parking lot. The soil was a Morley silt loam (Typic Hapludalf).
      Root zones within and downslope from the lot were dominated by alkaline soil
      reactions. Soil pH values along 15-m transects radiating from a white oak tree in
      a healthy stand upslope from the lot were predominantly acid beneath the crown,
      averaging between pH 5.5 and 6.1 to a depth of 90 cm within a 1.5 m radius of the
      tree trunk. Rainfall pH values varied from 4.3 to 5.9. Rainwater runoff from the
      parking lot and roadway varied from pH 7.5 to 8.0. Sampled in late summer,
      foliage of stressed trees in, and downslope from, the parking lot were all
      deficient in manganese (26-38 mg kg(-1)). It was concluded that Morley soils can
      be alkalinized by alkaline runoff from surfaces of calcium carbonate-containing
      structures, thereby reducing the solubility of soil manganese to a degree
      sufficient to cause deficiency of this element in white oaks.

PMID- 14975866
TI  - Effects of anaerobic growth conditions on phosphorus tissue concentrations and
      absorption rates of southern pine seedlings.
AB  - A non-circulating, continuously flowing solution culture was used to examine the
      long- and short-term effects of anaerobic growth conditions on phosphorus uptake
      in 12-week-old seedlings of three pine species. Sand pine (Pinus clausa (Engelm.)
      Sarg.) and a drought-hardy loblolly pine (P. taeda L.) had the largest reductions
      in biomass after 8 weeks in anaerobic solution, whereas the more flood-tolerant
      pond pine (P. serotina Michx.) and wet-site loblolly pine seedlings were least
      affected. Anaerobic growth conditions reduced P concentrations in the shoot and
      increased P concentrations in the root. Short-term (32)P-uptake experiments were
      conducted with intact seedlings to determine absorption rates (influx) of
      inorganic phosphate (Pi) by aerobically and anaerobically grown pine seedlings.
      Influx of Pi was weakly correlated with shoot fresh weight, root fresh weight,
      root P and shoot P per gram fresh weight root, suggesting that internal P levels
      and biomass influenced Pi absorption. The highest Pi absorption rates were found
      in anaerobically grown seedlings under anaerobic (32)P-uptake conditions. Of
      these, sand pine had the highest absorption rate in 50 microM KH(2)PO(4) (0.96
      micromol Pi g(-1) FW root h(-1)), and the wet-site loblolly pine exhibited the
      lowest rate (0.24 micromol Pi g(-1) FW root h(-1)). Aerobically grown seedlings
      had similar Pi absorption rates that were not significantly affected by O(2)
      concentration in the (32)P-uptake solution.

PMID- 14975867
TI  - Biomass, photosynthesis and water use efficiency of woody swamp species subjected
      to flooding and elevated water temperature.
AB  - Seedlings of water tupelo (Nyssa aquatica L.), bald cypress (Taxodium distichum
      (L.) Richard) and button bush (Cephalanthus occidentalis L.) and cuttings of
      black willow (Salix nigra Marshall) were established in pots and included in a
      complete factorial experiment with three water temperatures (maximums of about
      30, 35 or 40 degrees C) and three water levels (maximum flood depth was 6 cm
      above soil level). Flooding for 3 months at 30 degrees C reduced dry weight of
      roots and shoots in all species except water tupelo. At 40 degrees C, however,
      flooding significantly reduced growth of water tupelo as well as the other
      species. High water temperatures reduced stomatal conductance and photosynthetic
      rates in water tupelo and black willow, but not in the other species. In
      combination with flooding, high temperature reduced water use efficiency in all
      species except button bush and most sharply in water tupelo.

PMID- 14975868
TI  - Coupling of carbon and water interactions in forest stands.
AB  - Some measured values of the ratio transpiration rate/assimilation rate (E/A) for
      a Sitka spruce stand in Scotland and an oak-hickory stand are presented and
      compared with E/A for some agricultural crops. Typical midday values of E/A (on a
      molar basis) range from 100 to 900. Analysis suggests that this variation can be
      explained by differences in climate, canopy conductance and degree of coupling of
      the vegetation to the atmosphere. During the day, E/A varied considerably in the
      tree stands at the same time as there were changes in radiation, vapor saturation
      deficit and temperature. A lumped parameter, 'big leaf' model of canopy
      transpiration and assimilation was used to provide insight into how this complex
      of variables might influence E/A. The model predicted little response to
      radiation, but increase in E/A with increasing vapor saturation deficit and
      temperature, in agreement with the trends in the data. It was concluded that
      there is a great need for measurements of E/A of stands in relation to nutrient
      and water stress.

PMID- 14975869
TI  - Report on discussion of paper by P. G. Jarvis.
AB  - Unavailable

PMID- 14975870
TI  - Carbon x nutrient interactions-the limitations to productivity.
AB  - The interaction of nutrient cycles with the production, accumulation and death of
      organic matter is considered, in particular the relation to changes with stand
      age. It is shown that, because of efficient recycling within the tree and through
      the litter, the demands made by forests on the soil nutrient capital fall
      markedly after canopy closure. Because this effect is primarily a result of the
      ability of the tree to conserve and reuse nutrients in the foliage, the
      significance of the evergreen habit is examined. Although there are many reports
      of a net photosynthetic contribution from foliage older than one year, the
      relationships examined suggest that whereas there is virtually no correlation
      between growth rate and total foliage carried, there is quite a good relationship
      with weight of current-year foliage irrespective of whether trees are deciduous
      or the age at which evergreen foliage is shed. It is suggested that the evergreen
      habit would be a nutritional disadvantage prior to canopy closure but thereafter
      a considerable advantage.

PMID- 14975871
TI  - Report on discussion of paper by H. G. Miller.
AB  - Unavailable

PMID- 14975872
TI  - Interactions between carbon and nutrients in the forest ecosystem.
AB  - "There is little understanding of how improved plant nutrition increases the
      production of dry matter" (Linder and Rook 1984). Much of the work with forest
      trees has been at the broad level of concentration of nutrients, rather than with
      detailed physiological studies of nutrient response functions, of factors
      controlliing 'efficiency' of nutrient utilization, and of the redistribution of
      nutrients from aging to developing tissues. The sustained supply of nutrients in
      forest ecosystems depends on processes by which nutrients are cycled from plant
      (in organic combinations) to soil and back to plant (in simple inorganic form).
      Studies of the key processes of decomposition and mineralization, and of
      equilibria determining nutrient availability have been hampered by lack both of
      appropriate chemical methods and of methods that distinguish among fractions of
      organic matter of varying nutritional quality. The root systems of forests must
      also be studied more intensively. In particular, mechanisms by which nutrients in
      short supply are taken up (for example, the role of mycorrhizae and of
      specialized systems such as proteoid roots) and the redistribution of nutrients
      associated with turnover of the fine root system are fields for future research.

PMID- 14975873
TI  - Report on discussion of paper by P. M. Attiwill.
AB  - Unavailable

PMID- 14975874
TI  - Spatial considerations in physiological models of tree growth.
AB  - To include competitive interactions in a physiologically-based model of mixed
      growth-form plant communities presents a major methodological problem. This paper
      outlines a two-step solution: (1) a spatial framework for calculating a
      continuous surface that depicts the magnitude of influences of crowns, roots, and
      stems on resource availability, termed ECOLOGICAL FIELD THEORY (EFT), and (2) a
      mathematical technique for coupling water, light, and nutrients into a single
      growth equation using a physiologically-based continuous-time Markov approach,
      termed the CTM METHOD. Assumptions, limitations, and an application of the
      methodology to plant growth in a semiarid woodland community in Australia are
      presented.

PMID- 14975875
TI  - Report on discussion of paper by P. J. H. Sharpe.
AB  - Unavailable

PMID- 14975876
TI  - Experimental approaches to the study of the effects of nutrients and water on
      carbon assimilation by trees.
AB  - This paper outlines the experiemental approaches needed to provide detailed
      information about the effects of nutrients and water on carbon assimilation, and
      hence growth of trees. Data from a large multidisciplinary experiment being
      conducted in Australia illustrate important aspects of the approach advocated.
      The system model consists of a series of submodels describing the main
      physiological processes considered to govern the growth of trees. It is argued
      that field experiments designed to investigate physiological processes and their
      interactions should involve treatments that cause large differences in the growth
      rates of trees and in the condition of the trees at any time. The biomass of
      experimental stands should be defined. Measurements of stem and leaf growth,
      litterfall, leaf photosynthetic characteristics, plant water status and soil
      water content, plant nutrient status and nutrient mineralization rates in the
      soil provide the information needed to explain observed differences in growth and
      to refine the models underlying the research.

PMID- 14975877
TI  - Report on discussion of paper by J. J. Landsberg.
AB  - Unavailable

PMID- 14975878
TI  - Report on summary session.
AB  - Three participants were asked to contribute to a summary session on the last day
      of the symposium. They were invited to discuss the three major cycles of external
      phenomena that affect plant physiological processes; namely, the diurnal cycle,
      the wetting and drying cycle, and the annual cycle.

PMID- 14975879
TI  - Seasonal patterns of radial root growth and starch dynamics in plantation-grown
      Sitka spruce trees of different ages.
AB  - Seasonal patterns of radial root growth within 1 m of tree stems were examined in
      Scottish plantations of Sitka spruce trees aged 9, 15 and 20 years. Results were
      compared with parallel measurements of shoot extension, radial growth of stems
      and amounts of starch stored in tissues external to root wood. Youngest trees
      produced the largest annual increments in root cross-sectional area and numbers
      of new cells along radial files of tracheids. Irrespective of tree age, new cells
      were present in roots before bud burst and the onset of radial growth occurred
      progressively later with increasing distances from the stems. At ages 15 and 20,
      both stem cross-sectional area and radial root growth up to 0.5 m from the stem
      base had a minor peak of activity preceding and a major peak following shoot
      elongation. Further than 0.5 m from the stem, root growth was frequently
      restricted to the period following shoot extension. Starch storage in the roots
      reached a maximum in April and May, which was greatest for 9-year-old trees and
      least for 20-year-old trees. At all ages, radial root growth in early spring
      occurred concurrently with increased starch storage. Later in the season starch
      reserves declined rapidly during the period of shoot elongation and root growth
      occurred whilst reserves were low. At all ages for positions on the root at the
      base of the stem and 0.25 m from it, starch depletion, at its maximum rate during
      June, accounted for less than the measured increment of root wood growth at that
      point. This indicates a substantial translocation of substrates to these zones
      during growth. At the same time, the reduction in starch concentrations at more
      distal points from the stem far exceeded that required for local root thickening.

PMID- 14975880
TI  - Root growth potential, seedling morphology and bud dormancy correlate with
      survival of loblolly pine seedlings planted in December in Alabama.
AB  - First-year survival of December-planted loblolly pine seedlings sampled from 20
      nurseries ranged from 36 to 86%. Various characteristics of the seedlings
      including root growth potential (RGP), shoot/root ratio, root weight and stem
      length were correlated with survival. A regression model using the number of new
      roots >/= 0.5 cm and the shoot/root ratio accounted for 80% of the variation in
      first-year survival. Alone, the number of new roots >/= 0.5 cm accounted for 76%
      of the variation in survival. Foliar nutrients were not correlated with survival.
      Seedlings with a high proportion of quiescent buds at planting had a higher RGP
      and better survival than seedlings with dormant (endodormant) buds. The data
      suggest that seedlings with dormant buds should not be planted on sites where
      rapid new root growth is needed for survival.

PMID- 14975881
TI  - Water relations of loblolly pine seedlings from diverse geographic origins.
AB  - Leaf conductance at three absolute humidity deficits (AHDs) (7, 14 and 21 g m(
      3)), hydraulic conductance and components of tissue water potential were measured
      in one-year-old loblolly pine seedlings from six origins representing the
      geographic range of the species. Measurements were made on seedlings grown (a)
      with ample water (moist regime) and (b) with recurring severe drought (dry
      regime). However, all seedlings were well-watered prior to and during
      measurements. Seedlings grown in the moist regime had greater mean leaf
      conductances (0.30 versus 0.13 cm s(-1)) and greater responses to AHD than
      seedlings grown in the dry regime. They also exhibited greater hydraulic
      conductances (0.53 versus 0.35 microg cm(-2) s(-1) MPa(-1), less negative osmotic
      potentials (-1.45 versus -1.57 MPa) and higher relative water contents at turgor
      loss (0.72 versus 0.65). Seed source differences in water relations
      characteristics were detected only in seedlings grown in the moist regime. In
      these, trees from the three interior origins had greater mean leaf conductances
      than those from the three coastal sources (0.32 versus 0.28 cm s(-1)), but no
      differences in response to changing AHD were observed. Seedlings from North
      Carolina had lower osmotic potentials at turgor loss than those from Florida,
      Georgia or Texas. These differences in water relations characteristics are not
      clearly related to the observed greater survival ability of trees from interior
      origins compared with those from coastal origins.

PMID- 14975882
TI  - Douglas-fir and western larch: chemical and physical properties in relation to
      Douglas-fir bark beetle attack.
AB  - Frequency of Douglas-fir bark beetle, Dendroctonus pseudotsugae Hopkins
      (Coleoptera: Scolytidae), attack on western larch (Lark occidentalis Nutt.) was
      negatively correlated with 3-carene content of the xylem oleoresin.
      Concentrations of all oleoresin volatiles from stem cores of standing trees were
      higher in Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) than in western
      larch with the single exception of 3-carene. Successful brood production by the
      Douglas-fir bark beetle in standing trees of Douglas-fir but not western larch
      may therefore be explained, at least in part, by the high 3-carene content of
      western larch. Other differences between the species that might affect
      susceptibility to beetle attack include thinner phloem, higher phloem moisture
      content and larger diameter vertical resin ducts in western larch compared with
      Douglas-fir. Live standing western larch had no oleoresin exudation pressure,
      suggesting that this trait is not associated with resistance to attack by the
      Douglas-fir bark beetle in this species.

PMID- 14975883
TI  - In vitro regeneration of plantlets from embryonic and seedling explants of
      Engelmann spruce (Picea engelmannii Parry).
AB  - A protocol has been developed for the in vitro production of plantlets of
      Engelmann spruce. Embryos and various parts of Engelmann spruce seedlings formed
      multiple shoots when cultured on defined media containing a cytokinin. The site
      and time of occurrence of the shoot buds, as well as their number, differed in
      the various explants. The frequency of shoot-forming explants was influenced by
      the salt formulation used, the type and concentrations of cytokinins and their
      mode of application. Development of buds was achieved by transferring the
      explants to basal medium containing no growth regulators. Elongation of shoots
      was stimulated by reducing the concentration of salts and sugar, addition of
      activated charcoal and transferral to increased photoperiod and lower temperature
      regimes. Maximum rooting was induced by giving a pulse of high concentration of
      indolebutyric acid to the shoots. The roots developed within 8-10 weeks and the
      regenerated plantlets were transferred to soil under non-sterile conditions.

PMID- 14975884
TI  - Dormancy of micropropagated sour cherry plantlets.
AB  - Micropropagation of fruit trees results in the early onset of dormancy in the
      young plantlets. Prechilling of shoot cultures of sour cherry cvs Schattenmorelle
      and North Star at 4 degrees C for 6-8 weeks prolonged shoot extension of the
      plantlets but longer cold treatments adversely affected shoot growth and
      survival. Chilling of cultures had no affect on rhizogenesis. No significant
      influence of ABA, GA(3) or ABA + GA(3) was observed on root development.
      Gibberellic acid A(3) did not stimulate extension of the shoots, but when
      supplied together with ABA, it significantly decreased both shoot extension and
      the number of actively growing apices of plantlets of cv Schattenmorelle. The
      combined hormonal treatment had no effect on plantlets of the North Star cv.

PMID- 14975885
TI  - A dynamic model for studying flow of water in single trees.
AB  - Flow of water in a single tree was modeled in terms of the Darcy equation using a
      catena of four compartments: root, stem (further divided into discs), branches
      and leaves. Within each compartment or disc, water content was related to both
      water potential and conductivity of the xylem tissue using power or logarithmic
      functions, thus introducing both capacitance and variable resistance to flow in
      the model. Transpiration from the leaves to the atmosphere was used as the upper
      boundary to the model, and the soil-root interface as the lower boundary.
      Parameters for the water content, water potential and conductivity functions,
      together with physical dimensions were obtained by direct measurement or from the
      literature. A sensitivity analysis showed that the largest changes in simulated
      water potential and flow were associated with changes in the parameters directly
      controlling conductivity. Simulation of both smoothed diurnal changes and
      stepwise changes showed a phase lag down the tree, with flow tending to approach
      a steady state, but with changes in the gradients of water potential, water
      content and conductivity. A preliminary test of the model was made against field
      data using the Penman-Monteith equation to estimate the transpiration rate in a
      well-watered Pinus contorta Dougl. stand. Stem flow, water potential and water
      content were measured directly on a representative tree, which was subsequently
      harvested to provide dimensions and laboratory estimations of the parameters in
      the functions by direct measurement.

PMID- 14975886
TI  - Free proline changes in Pinus taeda L. callus in response to drought stress.
AB  - The amino acid, proline (PRO), may have an important role in plant adaptation to
      drought stress. To study the effect of drought stress on PRO content of pine
      tissues, we measured free PRO by high pressure liquid chromatography in control (
      -0.4 MPa) and drought-stressed ( -0.8, -1.0, -1.3, -1.6 MPa) callus tissue of
      Pinus taeda L. after eight weeks of growth. Drought stress was induced by adding
      polyethylene glycol (PEG) to the nutrient media. The relation between PRO
      accumulation and water potential was influenced by composition of the medium and
      temperature. Callus growing in media with water potentials of -0.8 MPa showed no
      increase in PRO compared to control callus in media at -0.4 MPa. When callus
      tissue was subjected to low water potentials (-1.6 MPa), endogenous PRO
      concentration increased 40-fold, while callus fresh weight decreased by more than
      90%. When exogenous PRO was added to the nutrient media, endogenous PRO was
      directly proportional to the exogenous PRO concentration rather than reduction in
      callus growth. Thus low water potential in callus results in endogenous PRO
      accumulation and large reductions in callus fresh weight growth. Proline
      accumulation in pine cells appears to be related to mechanisms associated with
      tolerance to desiccation.

PMID- 14975887
TI  - Determining nitrogen status of young loblolly pine by leaf reflectance.
AB  - Five-year-old lobloliy pine (Pinus taeda L.) seedlings were grown in sand culture
      in a completely randomized experimental design with eight nitrogen concentrations
      and three replications. Nitrogen concentration in the nutrient solution varied
      from 2 to 400 ppm. After a full growing season under treatment, percent
      reflectance of sunlight by new foliage was determined. Foliar samples were
      analyzed for nitrogen and chlorophyll. There was a strong positive correlation
      between nitrogen content and chlorophyll content (r = 0.895). The natural
      logarithm of percent reflectance was negatively correlated with both percent
      nitrogen content (r = -0.845) and chlorophyll content (r = -0.838). From these
      results, prediction equations for estimating nitrogen and chlorophyll content, as
      a function of reflectance, were formulated by regression analysis.

PMID- 14975888
TI  - Genetic and environmental control of crown development in Picea sitchensis and
      its relation to stem wood production.
AB  - Differences in stem wood production were found among four clones of Picea
      sitchensis (Bong.) Carr. at both an agricultural and a forest site. Clonal
      rankings were not consistent between the sites. Four variables were identified
      that may influence stem wood production, foliage amount, total aboveground
      production per unit foliage, proportional allocation of production to new foliage
      and to branch wood thickening. Comparison of clonal performance between sites
      showed that stem wood production could be influenced by differences in each of
      these variables. The four variables were themselves determined by components of
      crown structure, these were (i) production of new branches from the main stem,
      (ii) the numbers and lengths of branchlets supported on branches from the main
      stem, (iii) foliage production per unit branchlet length and foliage longevity,
      and (iv) branch wood thickening per unit branch length. These components varied
      both among clones and between sites. Branch production from the mainstem varied
      among clones, and for some clones it varied substantially between sites. In some
      clones branch production was positively correlated with mainstem height
      increment. There were differences among clones in the way that branchlet
      production varied between the agricultural and forest sites. In the absence of
      needle fall, foliage weight/branch length varied threefold among clones, but for
      each clone, varied little between sites. Branch wood weight/branch length was
      generally greater when foliage weight/branch length was large, but total branch
      wood increment/tree was strongly influenced by total branch length. The dynamics
      of crown development and its relation to stem wood production are discussed with
      reference to (i) the importance of needle longevity, (ii) the importance of
      tallness and narrowness of crowns and (iii) the importance of branch thickening,
      a process that competes with stem growth in the utilization of photosynthate. It
      is concluded that although each of these factors may be important, none singly
      accounts for the observed differences in stem wood production among genotypes and
      the way these change in response to the environment.

PMID- 14975889
TI  - Precision weighing lysimetry for trees, using a simplified tared-balance design.
AB  - Four weighing lysimeters (1.8 m diameter, 1 m depth, weight 3.5-4.5 Mg) were used
      to estimate transpiration from single, isolated trees. The weighing mechanism
      incorporated a simple, new system of wire ropes around torsion tubes, producing a
      lever action through which most of the weight was tared off with a counter
      weight. Weight differences measured by load cell under the main lever arm were
      unaffected by hysteresis or temperature change. Sensitivity better than 100 g was
      achieved in windless conditions. Daily measurements over yearly periods (trees
      could be regularly replaced using extra pots) revealed both sigmoid seasonal
      patterns, and sigmoid diurnal changes closely related to micrometeorological
      variables, for a range of tree species. Measurements taken during rainfall
      demonstrated that an isolated tree intercepts considerably more precipitation
      than does a uniform crop covering the same ground area, and that substantial
      evaporation from the canopy takes place while it is raining.

PMID- 14975890
TI  - Effects of pretreatment conditions on ammonium and nitrate uptake by Douglas-fir
      seedlings.
AB  - Effects of pretreatment solutions containing varying concentrations of calcium,
      potassium, ammonium and nitrate were evaluated by measuring fluxes of the same
      ions during a subsequent 4-hour uptake by Douglas-fir seedlings. Maximal rate of
      ammonium uptake (11 microeq g(-1) root dry weight h(-1)) was about 5 times faster
      than that of nitrate (2 microeq g(-1) root dry weight h(-1)). Ammonium uptake was
      most rapid after pretreatment with low potassium levels and was unaffected by
      ammonium pretreatment. Nitrate uptake was most rapid after pretreatment with high
      levels of nitrate and low levels of potassium. Calcium uptake was greater when
      nitrate replaced ammonium as the N source. High calcium pretreatment levels
      depressed subsequent calcium uptake or resulted in calcium release in both
      ammonium and nitrate experiments. Potassium efflux occurred with both N sources,
      but the release was less during nitrate uptake than during ammonium uptake.
      Efflux of potassium is probably associated with the high potassium status of the
      seedlings and the exchange between potassium and other cations. High levels of
      potassium in the pretreatment solutions enhanced potassium efflux and caused a
      reduction in the subsequent rates of uptake of both ammonium and nitrate. Length
      of pretreatment and seedling size generally did not affect uptake rates.

PMID- 14975891
TI  - Seed germination and seedling development in the mango (Mangifera indica L.).
AB  - Mango (Mangifera indica L., cv Ruby) seeds taken from ripe fruit showed no
      dormancy. They germinated at temperatures between 5 and 40 degrees C, but
      germination was most rapid near the upper end of this range (25-40 degrees C).
      The fresh seeds had a high moisture content (85%, dry weight basis) and quickly
      died on dehydration. The optimal temperature for growth of the seedlings was
      close to 30 degrees C. High temperatures (40 degrees C) and temperatures below 15
      degrees C were lethal. Growth of the stem occurred in successive flushes
      separated by rest periods. When the leaves of the preceding flush finished
      growing, the axis lengthened beneath the apical bud.

PMID- 14975892
TI  - Relationships among drought resistance, transpiration rates, and abscisic acid
      levels in three northern conifers.
AB  - Water potentials, transpiration rates and abscisic acid (ABA) levels in shoots of
      black spruce (Picea mariana (Mill.) BSP), white spruce (Picea glauca (Moench)
      Voss) and jack pine (Pinus banksiana Lamb.) seedlings were monitored during
      periods of drought and recovery from drought. Abscisic acid contents of shoots
      increased during the period of drought as water potentials decreased. The
      increase in levels of ABA was closely associated with a decrease in rates of
      transpiration. In the spruces, the levels of ABA peaked and then fell while plant
      water potentials continued to decrease, whereas in jack pine, the level of ABA
      rose throughout the drought treatment. After rewatering, the levels of ABA in all
      three conifers fell concurrent with a rise in transpiration rates. At the end of
      the three-day recovery period, ABA levels and transpiration rates in the spruces
      were either at or near control levels, whereas the concentration of ABA in jack
      pine remained approximately twice the control level, and transpiration was only
      60% of the control rate. A compound tentatively identified as phaseic acid
      followed trends similar to those for ABA.

PMID- 14975893
TI  - Foliar mineral composition, fertilization and dieback of Norway spruce in the
      Belgian Ardennes.
AB  - Needles from healthy Norway spruce (Picea abies (L.) Karst.) at Willerzie in the
      West Ardennes and from trees with symptoms of dieback at Langesthal in the East
      Ardennes were analyzed by age class for mineral composition. Both stands were on
      acid oligotrophic soils. At Willerzie, needles were sampled from plots fertilized
      12 to 17 years earlier (dolomitic lime plus N, P and K) as well as unfertilized
      plots. Effects of fertilization included increased levels of calcium, manganese,
      phosphorus, and copper and reduced levels of total sulfur, sulfate-S, sulfate
      S:total S, potassium and aluminum. Levels of calcium, magnesium, copper and boron
      were low at both sites and, at Langesthal, calcium and magnesium may have been
      deficient. Sulfur level was normal at Willerzie, but at Langesthal, mean sulfur
      content for needles of all age classes was 198 mg 100 g(-1) dry weight, a level
      that may be toxic. In older needles, the N:S ratio at Langesthal was below the
      threshold value of eight reported to be necessary for healthy growth. Other
      symptoms of stress observed were high sulfate-S:total S and nitrate-N:total N
      ratios. At Langesthal, manganese level was probably adequate although only one
      fifth the level at Willerzie. Levels of aluminum and iron were very high at both
      sites. Most of the iron and much of the aluminum occurred as a surface deposit
      that could be removed by washing the needles in chloroform.

PMID- 14975894
TI  - Factors contributing to forest decline in northwestern Switzerland.
AB  - Possible causes of decline of 37 beech (Fagus sylvatica L.) forests in
      northwestern Switzerland were investigated. The trees were assessed for symptoms
      of damage or disease including loss of leaves, chlorosis and dead shoots. In
      addition, nutrients and pollutants were analyzed in soil, leaves, stemflow and
      rainwater. Air pollutants were monitored at several sites. The results indicate
      that a variety of factors may have contributed to forest decline.

PMID- 14975895
TI  - Effects of temperature on shoot growth in northern provenances of Pinus
      sylvestris L.
AB  - Effects of temperature on shoot growth in northern provenances of Pinus
      sylvestris L. were studied under natural long-day conditions (Lat. 69 degrees 39'
      N) at controlled temperatures. The optimum constant temperature for formation of
      stem unit primordia in the terminal resting bud was 18 to 21 degrees C. Stem unit
      number decreased linearly with temperature between 15 and 9 degrees C.
      Temperature during bud formation had a significant effect on final stem unit
      length achieved in the following year. Final shoot length was significantly
      affected by temperature during shoot elongation. The optimum constant temperature
      for elongation growth was 18 to 21 degrees C. The rate of shoot elongation was
      positively correlated with the number of stem units.

PMID- 14975896
TI  - Physiological, environmental and genetic variation in apical dominance as
      determined by decapitation in Triplochiton scleroxylon.
AB  - Patterns of lateral shoot growth following decapitation in 1-meter tall, rooted
      Triplochiton scleroxylon K. Schum. cuttings varied with clone and in response to
      a range of environmental conditions and growth regulator treatments. Two phases
      of bud activity were identified, the Sprouting Phase, in which many buds were
      released from correlative inhibition, and the Dominance Phase (starting 3-4 weeks
      after decapitation) in which uppermost laterals began to dominate and suppress
      growth, and sometimes cause apical abscission of lower lateral shoots. Except in
      non-erect plants, the most distal lateral to elongate became the new leading
      shoot. During the Sprouting Phase, the proportion of active buds was increased by
      removing leaves from the upper part of the stem, and by reducing the photoperiod
      from 13-15 h to 11 h, particularly at 20 degrees C rather than 25 degrees C.
      Conversely, the proportion of sprouting buds was decreased by injecting plant
      stems with NAA (250 microg/plant). During the Dominance Phase, suppression of
      lateral shoot growth was hastened by stem injection with GA(3) (200
      microg/plant), especially when applied to the uppermost shoot at the end of the
      Sprouting Phase. Reimposition of dominance was delayed, however, by (1) high
      rates of N:P:K fertilization, (2) low temperature (20 versus 25 degrees C) under
      relatively long days (13 and 15 h), (3) low photon flux density (160 micromol m(
      2) s(-1)) and (4) severe defoliation. Plant orientation had no effect on bud
      activity of decapitated plants, but affected the relative vigor and orientation
      of new lateral shoots. High temperature (25 versus 20 degrees C) and injection
      with GA(3) increased the erectness of newly developing lateral shoots.

PMID- 14975897
TI  - Leaf growth characteristics of fast-growing poplar hybrids Populus trichocarpa x
      P. deltoides.
AB  - Fast-growing hybrid poplar trees (Populus trichocarpa Torr. & A. Gray x P.
      deltoides Bartr. ex Marsh.) were compared with slower-growing parental types in
      both field and laboratory experiments to determine physiological components of
      leaf growth that could be closely related to biomass production. Stem volume was
      correlated with individual leaf area (r = 0.81) and leaf growth rate (r = 0.82).
      Hybrids had a greater total leaf area, not because they produced more leaves, but
      because they had larger leaves than either parental type. The greater leaf size
      of the hybrids may be explained by inheritance of larger cell number from P.
      deltoides and larger cell size from P. trichocarpa. Rates of enlargement of
      isolated leaf discs in liquid culture were approximately 50% of those observed in
      intact leaves of field-grown plants.

PMID- 14975898
TI  - Comparison of yellow poplar growth models on the basis of derived growth analysis
      variables.
AB  - Quadratic and cubic polynomials, and Gompertz and Richards asymptotic models were
      fitted to yellow poplar growth data. These data included height, leaf area, leaf
      weight and new shoot height for 23 weeks. Seven growth analysis variables were
      estimated from each function. The Gompertz and Richards models fitted the data
      best and provided the most accurate derived variables. However, the Richards
      model was more complex to fit.

PMID- 14975899
TI  - Relationships between respiratory activity and water-soluble sulfhydryl content
      of Norway spruce needles.
AB  - The rate of respiration of spruce needles was affected by the level of foliar
      glutathione. At 37 degrees C the rate of respiration increased with increasing
      water-soluble sulfhydryl content up to 1.3 micromol g(-1) fresh weight. Higher
      thiol concentrations inhibited the rate of respiration. At 25 degrees C no
      relationship was observed between glutathione content and rate of respiration. It
      was concluded that the mechanism by which SO(2) affects plants is temperature
      dependent.

PMID- 14975900
TI  - Tissue culture and the propagation and genetic improvement of conifers: problems
      and possibilities.
AB  - The utilization of tissue culture in the propagation and genetic improvement of
      conifers holds promise of many benefits including faster multiplication of
      selected genotypes, faster development of improved genotypes and the transfer of
      genes between non-fertile parents. However, many of the techniques required for
      the realization of this potential remain to be developed. Furthermore, genetic
      differentiation of cells in culture creates uncertainty as to the fidelity of
      reproduction by micropropagation. Aspects of the problem of nuclear DNA variation
      during reproduction by tissue culture are reviewed with particular reference to
      the genus Pinus.

PMID- 14975901
TI  - Boron and ectomycorrhizal influences on indole-3-acetic acid levels and indole-3
      acetic acid oxidase and peroxidase activities of Pinus echinata Mill. roots.
AB  - The level of indole-3-acetic acid (IAA) in shortleaf pine (Pinus echinata Mill.)
      roots was increased by inoculation with the ectomycorrhizal fungus Pisolithus
      tinctorius (Pers.) Coker and Couch. Indole-3-acetic acid oxidase activity was
      also increased suggesting that the increased level of IAA was the result of
      increased synthesis. Boron fertilization reduced IAA levels in roots inoculated
      with P. tinctorius but not in noninoculated roots.

PMID- 14975902
TI  - An estimate of the photosynthetic production of individual trees in a
      Chamaecyparis obtusa plantation.
AB  - A Weibull function was used to model the vertical distribution of leaf area of
      individual trees in a 25-year-old Chamaecyparis obtusa (Siebold & Zucc.) Endl.
      plantation. The parameter representing the shape of the leaf distribution was
      independent of tree size. A scale parameter tended to decrease with tree size
      suggesting a critical minimum height for retention of foliage by trees. On the
      basis of leaf distribution, the photosynthetic production of individual trees was
      estimated from the canopy photosynthetic production, which was determined from a
      model of canopy photosynthesis. The data indicated that the photosynthesis of a
      tree was proportional to the corresponding tree weight to the power of 1.84.
      Furthermore, the photosynthetic production varied as the 3/2nd power of total
      leaf area of the tree. Thus, it was concluded that the photosynthetic production
      per unit of leaf area, that is, the mean photosynthetic activity of a tree, is
      proportional to the stem girth at clear length, or the square root of the leaf
      area of the tree.

PMID- 14975903
TI  - Sustained division of protoplast-derived cells from primary leaves of Pinus
      pinaster, factors affecting growth and change in nuclear DNA content.
AB  - Leaf protoplasts were isolated from apical and in vitro-induced axillary buds of
      Pinus pinaster Ait. seedlings. First divisions were seen after 8-10 days of
      culture in a 650 mOsm kg H(2)O(-1) medium in which glutamine was the sole
      nitrogen source. Colony formation was achieved in 6-7 weeks in a modified
      protoplast culture medium in which a reduction in the concentrations of both
      calcium and carbon was essential for sustained divisions. To maintain cell
      suspension growth, it was necessary to subculture every three weeks to a 170 mOsm
      kg H(2)O(-1) medium. Lowering the C/N ratio did not support better growth.
      Phenolic compounds were detected in stationary phase cultures. Analysis by HPLC
      indicated that the cinnamate pathway was involved in their synthesis. After 3 and
      7 months of culture, 65 and 74%, respectively, of protoplast-derived cells had a
      nuclear DNA content comparable to that of leaf protoplasts.

PMID- 14975904
TI  - Seasonal variation in the biomass and non-structural carbohydrate content of fine
      roots of teak (Tectona grandis L. f.) plantations in a dry tropical region.
AB  - Seasonal variation in the biomass and total non-structural carbohydrate content
      (TNC) of fine roots of teak (Tectona grandis L. f.) were studied in 19- and 29
      year-old plantations in a dry tropical region. Fine root TNC content was highest
      during the dry summer (May), and lowest in the early part of the rainy season
      (July). Generally, seasonal trends in TNC content were the opposite of those in
      fine root biomass. The TNC concentration of roots increased with diameter and
      decreased with soil depth. In the 19-year-old plantation, fine root TNC content
      was approximately 12% higher than in the 29-year-old plantation.

PMID- 14975905
TI  - Effects of atmospheric humidity and acclimation temperature on the temperature
      response of photosynthesis in young Larix decidua Mill.
AB  - Larch (Larix decidua Mill.) seedlings of a low altitude (600 m) Austrian
      provenance were raised outdoors and acclimated in chambers for 14 to 24 days
      during August and September at either 8 degrees C and an atmospheric saturation
      vapor pressure deficit (DeltaW) of 2.5 Pa kPa(-1), or 24 degrees C and a DeltaW
      of 6.2 Pa kPa(-1). Subsequently, their rates of photosynthesis, dark respiration
      and transpiration were measured at temperatures between 5 and 30 degrees C with
      DeltaW either maintained below 10 Pa kPa(-1) or allowed to increase with
      temperature up to 38 Pa kPa(-1). Below 15 degrees C the photosynthetic rate of
      cold-acclimated plants was higher, but above 15 degrees C it was lower, than that
      of warm-acclimated plants. Temperature acclimation caused a greater shift in the
      temperature optimum for photosynthesis when DeltaW was kept small than when it
      was allowed to increase with temperature. When DeltaW was kept small, leaf
      conductance of cold-acclimated plants, unlike that of warm-acclimated plants, did
      not increase with temperature above 15 degrees C. When DeltaW increased with
      temperature, leaf conductance of cold-acclimated plants decreased more rapidly
      with temperature than that of warm-acclimated plants. Low temperature acclimation
      increased the rate of photosynthesis below 15 degrees C without affecting leaf
      conductance, which indicates that there was an adaptation in leaf internal
      processes. Further evidence of a metabolic adaptation to acclimation temperature
      is that dark respiration of cold-acclimated plants was twice that of warm
      acclimated plants at all temperatures.

PMID- 14975906
TI  - An effect of gravity on bud-burst in balsam fir.
AB  - Bud-burst on first order lateral branches of Abies bafsamea L. (balsam fir) was
      delayed when the branches were rotated 180 degrees about their long axis. This
      was not a consequence of injury caused by the treatment because buds rotated 180
      degrees on inverted plants flushed at the same time as the controls, whereas
      flushing of all other buds was delayed. Buds thus appear to be more vigorous when
      maintained in the same orientation to gravity in which they are formed and the
      site of gravitational stimulus perception appears to be the bud itself. Except on
      the leading shoot, leaves from inverted buds turned so that their adaxial surface
      faced upward, unless there was intense illumination from below. However, both
      anisophylly and positioning of leaves on lateral shoots were apparently
      predetermined because the shorter, more forward pointing leaves appeared below
      the longer distichous leaves on shoots from inverted buds. Shoots with normally
      oriented leaves appeared the next season.

PMID- 14975907
TI  - Ribulose-1,5-bisphosphate carboxylase activity of Populus tremuloides Michx. bark
      tissues.
AB  - Ribulose-1,5-bisphosphate (RubP) carboxylase was isolated from bark tissue of
      Populus tremuloides Michx. by a one-step Sephadex G l00-120 column chromatography
      procedure. The peak fraction had specific activity of 1.3 micromol CO(2) mg(-1)
      chlorophyll min(-1). The bark RubP carboxylase activity was comparable to that of
      leaf tissues. Thus, young corticular tissues are photosynthetically competent and
      contain sufficient RubP carboxylase to account for the reported rates of
      photosynthesis.

PMID- 14975908
TI  - Germination of Eucalyptus sieberi, L. Johnson seeds. I. Response to substrate and
      atmospheric moisture.
AB  - Consistent germination of Eucalyptus sieberi L. Johnson seeds required a low
      vapor pressure deficit (< 5 x 10(-6) MPa) and a high matric water potential (> -5
      x 10(-3) MPa). Eucalyptus sieberi seeds, under moist but less favorable
      conditions, were unable to germinate but underwent changes that enabled them to
      germinate more rapidly when suitable conditions occurred. Such pregerminative
      development was interrupted but not reversed by a dry period as long as eight
      months. This may explain how seeds of this species germinate successfully on the
      surface of exposed seedbeds subject to intermittent drying.

PMID- 14975909
TI  - Germination of Eucalyptus sieberi L. Johnson seeds. II. Internal water relations.
AB  - At 15-20 degrees C, seeds of Eucalyptus sieberi L. Johnson need to maintain a
      water content equal to 30% or more of dry weight for approximately 60 h in order
      to germinate. Several shorter periods of imbibition at 30% water content
      separated by between 6 and 120 h desiccation were as effective as an unintenupted
      imbibition in bringing seeds to the point of germination. Even after 8 months'
      desiccation an earlier imbibition shortened the time required for the completion
      of germination, although it did not hasten the onset of germination. The water
      potential of seeds sufficiently hydrated to germinate was about -0.6 MPa, whereas
      that of the embryo was only about -4.5 MPa. The difference was caused by the
      inhibition of water uptake by the inner integument of the seed coat. During
      germination, reserve protein in a small group of cells above the collet was
      hydrolyzed. Subsequent expansion of these cells caused rupture of the inner
      integument thereby allowing further water uptake by the embryo. The balance of
      water absorption and evaporative loss by the outer integument was such that most
      seeds on a moist substrate but exposed to dry air (6.5-8 x 10(-4) MPa) did not
      maintain the 30% water content necessary for germination. Thus although able to
      germinate on seedbeds subject to intermittent drying, E. sieberi seeds have the
      capacity to avoid germination except under humid conditions.

PMID- 14975910
TI  - Effects of ABA application on cessation of shoot elongation in long-day grown
      Norway spruce seedlings.
AB  - Abscisic acid (ABA) was applied in lanolin to apical buds of Norway spruce (Picea
      abies (L.) Karst.) seedlings actively growing in a 24 h photoperiod. At a rate of
      100 microg per plant, ABA suspended shoot elongation for about three weeks in the
      majority of plants but failed to induce normal winter buds. The role of ABA in
      the induction of dormancy is thus uncertain in conifers as well as in deciduous
      woody plants.

PMID- 14975911
TI  - The electrical conductivity of Norway spruce needle diffusate as affected by
      certain air pollutants.
AB  - Four-year-old potted Norway spruce (Picea abies (L.) Karst.) grafts established
      with scion material from three mature trees, were exposed to either long-term
      fumigation with SO(2), with and without water stress, or long-term ozone
      fumigation. The electrical conductivity of the needle diffusate was measured
      after the needles had been washed with chloroform and then leached in distilled
      water. Although none of the treatments caused visible symptoms of injury, SO(2)
      fumigation and water stress both caused an increase in diffusate conductivity,
      but the effects were not synergistic. Ozone fumigation lowered both conductivity
      and nutrient ion concentration in the leachate.

PMID- 14975912
TI  - Effect of GA(4 + 7) on the initiation and development of the inflorescence bud of
      evergreen azalea.
AB  - Apical buds of evergreen azalea (Rhododendron sp.) were treated with GA(4 + 7) at
      different stages of development. Treatment of vegetative buds stimulated shoot
      growth, slightly delayed both flower initiation and development, but increased
      the number of flower primordia. Treatment at the time of floral transition
      induced bud abortion at an early stage of the reproductive development. Treatment
      of inflorescence buds which contained at least one complete flower substituted
      for chilling in overcoming dormancy and prevented inflorescence bud abortion.

PMID- 14975913
TI  - Effects of gibberellin A(4 + 7) and bark-ringing on cone initiation in mature
      Picea sitchensis grafts.
AB  - Large numbers of cones (strobili) were induced in a 10-year-old plot of mature
      grafts of Picea sitchensis (Bong.) Carr. All trees injected with 20 mg GA(4 + 7)
      in June initiated female and male cones in the same year. This treatment
      increased the number of female cones per plant 12-fold above the controls, more
      than doubling the percentage of cones that were female. Complete bark-ringing
      (done in May of the previous year) showed an additive effect with GA on the
      number of female cones formed, but a negative interaction on the number of male
      cones induced. Ringing promoted male cone production most when used alone.
      Treatments, singly or combined, also increased the proportion of cones that were
      lateral, compared with the preponderance of terminal male cones in the controls.
      The effects were apparently not directly associated with alterations in
      vegetative vigor, although these occurred causing a reduction in the proportion
      of buds containing vegetative shoots the following year. The clones differed in
      most characteristics, but both sparse and prolific clones were induced to
      reproductive activity. Viable seed yields per tree, and notional production from
      seed-orchards were enhanced almost 10-fold by GA injection, and about 4-fold by
      bark-ringing and GA + bark-ringing.

PMID- 14975914
TI  - Influence of gibberellic acid and stock plant irradiance on carbohydrate content
      and rooting in cuttings of Scots pine seedlings (Pinus sylvestris L.).
AB  - Seedlings of Pinus sylvestris L. were grown at three different irradiances (12,
      30, or 60 W m(-2)) under a 17 h photoperiod. After six weeks, cuttings were
      excised and rooted at 30 W m(-2). Gibberellic acid (GA(3), 5 microl of 2 x 10(-4)
      or 2 x 10(-3) M) was applied to each cutting immediately after excision. Cuttings
      from stock plants grown at the low irradiance rooted most quickly, whereas the
      highest number of roots per cutting was obtained in cuttings from stock plants
      grown at 30 W m(-2). Gibberellic acid delayed rooting and reduced the number of
      roots in cuttings from stock plants grown at 12, 30, or 60 W m(-2). The initial
      carbohydrate content of cuttings increased with stock plant irradiance. For all
      carbohydrates, except myoinositol and an unknown inositol derivative, the content
      per cutting increased during the first 28 days of rooting. The GA(3) treatment
      significantly reduced the starch content of cuttings during the rooting period,
      but did not significantly change the content of ethanol soluble carbohydrates.

PMID- 14975915
TI  - Evaluation of transpiration in a Douglas-fir stand by means of sap flow
      measurements.
AB  - Transpiration of a Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) stand was
      evaluated by sap flow measurements during a 4-month period. Between-tree
      variation in sap flow depended on crown class. On a sunny day, total
      transpiration was 1.6, 8.0 and 22.0 liters day(-1) for suppressed, codominant and
      dominant trees, respectively. Transpiration estimated by sap flow fell below
      potential evapotranspiration when available soil water decreased below 30% of its
      maximum value. Sap flow measurements gave transpiration values similar to those
      obtained by the water balance method.

PMID- 14975916
TI  - Adaptations to soil drying in woody seedlings of African locust bean, (Parkia
      biglobosa (Jacq.) Benth.).
AB  - Stomatal conductance, transpiration and xylem pressure potential of African
      locust bean (Parkia biglobosa (Jacq.) Benth.) seedlings subjected from the sixth
      week after emergence to four weeks of continuous soil drought did not differ from
      those of well-watered, control plants until two-thirds of the available soil
      water had been used. In both well-watered and drought-treated plants, stomatal
      conductance was highest early in the day when vapor pressure deficits were low,
      but decreased sharply by midday when evaporative demand reached its highest
      value. There was no increase in stomatal conductance later in the day as vapor
      pressure deficit declined. The relationship between transpiration rate and xylem
      pressure potential showed non-linearity and hysteresis in both control and
      drought-treated plants, which seems to indicate that the plants had a substantial
      capacity to store water. The rate of leaf extension in African locust bean
      seedlings subjected to six consecutive 2-week cycles of soil drought declined
      relative to that of well-watered, control plants, whereas relative root extension
      increased. It appears that African locust bean seedlings minimized the impact of
      drought by: (1) restricting transpiration to the early part of the day when a
      high ratio of carbon gain to water loss can be achieved; (2) utilizing internally
      stored water during periods of rapid transpiration; (3) reducing the rate of leaf
      expansion and final leaf size in response to soil drought without reducing the
      rate of root extension, thereby reducing the ratio of transpiring leaf surface
      area to absorbing root surface area.

PMID- 14975917
TI  - Variation in water relations of black spruce stock types planted in Ontario.
AB  - Upland, intermediate and lowland sites in northeastern Ontario were planted
      between May 28 and June 8 with three types of black spruce (Picea mariana (Mill.)
      BSP) nursery stock: (1) spring-lifted, 1.5 + 1.5 bareroot plants (BR); (2) 24
      week-old, winter-sown, container stock (CWS); and (3) spring-sown, overwintered,
      container stock (CO). At the beginning of the growing season, the BR stock had
      the lowest xylem pressure potentials (Psi(x)), stomatal conductances (g(wv)), and
      net photosynthetic (P(n)) rates. By the end of the growing season, the BR stock
      still had lower g(wv)s than the container stock types, but had higher shoot
      Psi(x) values. In August, the turgor loss points for the BR, CO and CWS stock
      types were -2.8, -1.93 and -1.6 MPa, respectively, while the minimum observed
      shoot Psi(x) values were -1.4, -1.7 and -1.9 MPa, respectively. The BR stock
      produced the greatest dry weight of new shoots and unsuberized roots. No new
      shoots were produced by the CWS stock, but they produced a greater dry weight of
      unsuberized roots than the CO stock. As a percent of the dry weight of suberized
      roots, the greatest production of unsuberized roots was by the CWS stock, the
      least by the BR trees.

PMID- 14975918
TI  - Growth and the composition and transport of carbohydrate in compatible and
      incompatible peach/plum grafts.
AB  - The growth of scions and rootstocks of compatible (Prunus persica L. Batsch cv.
      Springtime/Prunus cerasifera L. Ehrh. cv. myrobolan P2032) and incompatible
      (Prunus persica L. Batsch cv. Springtime/Prunus cerasifera L. Ehrh. cv. myrobolan
      P18) peach/plum grafts were compared. The composition of soluble carbohydrates in
      phloem and cortical tissues of both peach/plum grafts and ungrafted plums and the
      translocation of these compounds across the union of grafted plants were
      examined. Sorbitol and sucrose were the dominant sugars in the phloem and
      cortical tissues of plum. A cyanogenic glycoside, prunasin, was present in peach
      tissues in amounts equivalent to those of sorbitol or sucrose, whereas only small
      amounts of prunasin were detected in plum tissues. The concentration of prunasin
      was significantly higher in the phloem of the P18 rootstock of the incompatible
      graft. Sorbitol was the only sugar significantly depleted in rootstock tissues of
      the incompatible graft when the first foliar symptoms of graft incompatibility
      became evident. Translocation studies with 1-(14)C-deoxyglucose showed that the
      relative distribution of radioactivity across the graft union was similar in both
      compatible and incompatible grafts. However, the total amount of radioactivity
      translocated across the incompatible graft was less than one-third of that
      translocated across the compatible graft. The results are consistent with the
      hypothesis of a progressive poisoning of the root system in the incompatible
      graft by a compound synthesized in peach foliage. The role of prunasin as a
      possible candidate is discussed.

PMID- 14975919
TI  - Young's modulus of sections of living branches and tree trunks.
AB  - Young's modulus along the grain (elasticity, E) was measured on 10 sections of
      branches and three tree trunks, with bark, of Picea sitchensis (Bong.) Carr.,
      Pinus contorta Dougl. ex Loud., Larix decidua Mill. and Betula pendula Roth. syn.
      verrucosa Ehrh. The sections were simply supported and corrections were made for
      taper and deflection due to shear. The E values for trunks were at the lower end
      of the range reported for green timber (2.4-7.5 GPa), and those for branches were
      still lower (0.7-4.6 GPa). Values of E for branches decreased with decrease in
      specific gravity, which corresponded with an increase in percentage water
      content. When E values were calculated using underbark diameters they fell more
      closely within the range reported for green timber.

PMID- 14975920
TI  - Structural analysis of tree trunks and branches: tapered cantilever beams subject
      to large deflections under complex loading.
AB  - The dimensions, deflections and support costs of tree trunks and branches can be
      deduced using the structural theory for cantilever beams. However, elementary
      theory applies only as long as deflections are small, and complex analytical
      solutions are required to account for complex taper and patterns of loading. This
      paper describes a method that copes with large deflections, any patterns of
      taper, and any patterns of distributed loading, point loading or externally
      applied bending moments. A beam is considered to be composed of a series of short
      segments, such that each has only a small deflection, and each can have specified
      dimensions, Young's modulus and loading. The transport matrix method of
      structural analysis is used to determine the end conditions of each segment and
      of the whole beam. The method is verified by comparing predicted deflections with
      deflections (a) calculated using an analytical solution by Bisshopp and Drucker
      (1945), (b) calculated and measured for sapling tree trunks by Leiser and Kemper
      (1968), and (c) measured on tapered and untapered plastic rods.

PMID- 14975921
TI  - Ecophysiological characteristics of the seed of the tropical forest pioneer Urera
      caracasana (Urticaceae).
AB  - Urera caracasana (Jacq.) Griseb is a small, fast-growing evergreen pioneer tree
      which colonizes openings in the tropical rain forest of 'Los Tuxtlas', Veracruz,
      Mexico. Annual seed production by 10 trees was estimated to range from 0.4 x
      10(5) to 1.6 x 10(6) seeds per tree. Fifteen species of resident and migratory
      birds were observed to visit the plants and disperse the seeds. Most seeds
      imbibed in petri dishes placed on the forest floor beneath a small opening in the
      canopy, where the red/far-red ratio of the light was around 1.0, germinated
      within 2 weeks. Germination beneath the forest canopy, where the red/far-red
      ratio of the light was approximately 0.2, was much slower and did not exceed 40%.
      A minimum of 4 h daily exposure to unfiltered natural light was required for
      rapid germination in the forest. In the laboratory rapid germination at 25
      degrees C required a minimum of 4 h white light. However, if temperature during
      the light period was 35 degrees C, 30 min exposure to white light daily was
      sufficient to induce germination. Seeds that failed to germinate when imbibed for
      60-360 days in petri dishes placed on the forest floor beneath the forest canopy,
      germinated rapidly in the laboratory when held at 25 degrees C and exposed daily
      to 12 h white or red light. Seeds imbibed for 120 days or more beneath the forest
      canopy were also induced to germinate by 12 h daily exposure to far-red light
      when this was combined with a 35/25 degrees C day/night temperature regime. Seeds
      buried in vermiculite-filled nylon mesh bags disappeared rapidly with few
      remaining after 2 months. Seeds that survived remained viable and germinated when
      incubated in petri dishes at 25 degrees C. Initially, buried seeds required light
      for germination. However, after 17 months' burial, seeds germinated in darkness
      when transferred to the laboratory and incubated on agar at 25 degrees C.

PMID- 14975922
TI  - Rapid field measurement of the assimilation rate versus internal CO(2)
      concentration relationship in green ash (Fraxinus pennsylvanica Marsh.): the
      influence of light intensity.
AB  - Assimilation rate (A) versus intercellular CO(2) concentration (C(i))
      relationships for leaflets of five-year-old green ash (Fraxinus pennsylvanica
      Marsh.) trees were computed from gas exchange measurements obtained in the field
      with a closed-circuit, portable photosynthesis measurement system comprising an
      LI-6200 gas analyzer and an LI-6000 computer, (Li-Cor, Inc., Lincoln, Nebraska,
      USA). Observations were made over a range of light intensities achieved by
      attenuating direct sunlight with neutral density filters, and over a range of
      ambient CO(2) concentrations achieved by breathing into the assimilation chamber
      and then lowering the CO(2) concentration to the desired level with the LI-6200's
      soda-lime scrubber. Boundary layer conductance was determined by use of a leaf
      replica made of moist filter paper. Typically, A-C(i) curves at four light
      intensities were obtained in three to four hours. The initial slope (when A = 0)
      of the A-C(i) curve obtained at a light intensity of 1750 micromol m(-2) s(-1)
      (full sunlight) was similar to that obtained at a light intensity of 840 micromol
      m(-2) s(-1). However, when light intensity was reduced further (to 370 and 160
      micromol m(-2) s(-1)), the initial slope of the A-C(i) curve also decreased,
      indicating that at these light intensities, assimilation was limited by
      photochemical energy supply, as well as CO(2) concentration.

PMID- 14975923
TI  - A semi-automated data processing system for root growth analysis: application to
      a growing oak seedling.
AB  - A data acquisition and processing system for analyzing root structure and growth
      is presented. Two-dimensional drawings are made of root systems growing against
      the inclined, transparent wall of a rhizotron. For analysis, a root is treated as
      a number of straight segments between points determined by the position of root
      apices at successive times of observation and the insertion points of lateral
      roots. The coordinates of the points are digitized by means of a graphics tablet
      and the description of the root system completed with information about root
      branching pattern and root order. From the recorded data, various root
      characteristics and growth parameters can be computed with a program available
      from the authors. Use of the data processing system in studies of root
      architecture is discussed and its application in the analysis of root growth of a
      pedunculate oak seedling (Quercus robur L.) reported.

PMID- 14975924
TI  - Programming of adult cardiovascular function after early maternal undernutrition
      in sheep.
AB  - The prenatal nutritional environment influences the subsequent risk of
      hypertension in adulthood. Animal studies have used, generally, the rat as a
      model species to illustrate the association between maternal nutrient intake and
      blood pressure in the resulting adult offspring. No study to date has shown
      programming of adult cardiovascular function in the sheep through maternal
      dietary intervention. We therefore fed pregnant sheep to either 100% recommended
      intake from day 0 of gestation to term [ approximately 147 days gestational age
      (dGA); controls n = 8] or to 50% recommended intake from day 0 to 95 dGA and
      thereafter to 100% intake (NR; n = 9). Sheep lambed naturally, offspring were
      weaned at 16 wk, and the male offspring were reared on pasture until 3 yr of age.
      At this time, cardiovascular catheters were inserted under halothane anesthesia
      and sheep were allowed 2-4 days recovery. Basal cardiovascular status and pressor
      responses to infusion of norepinephrine, angiotensin II, and captopril were then
      assessed alongside basal plasma concentrations of glucose, cortisol, and leptin.
      NR sheep were of similar birth weight to controls but at 3 yr of age had higher
      blood pressure before, but not after, feeding. Peripheral sensitivity to
      vasoconstrictor infusion was similar between dietary groups, although a reflex
      bradycardia was not apparent in NR sheep during norepinephrine infusion.
      Circulating leptin correlated well with fat mass and increased more after
      vasoconstrictor infusion in NR sheep. In conclusion, early NR has been shown to
      program aspects of cardiovascular control and adipocyte function in adult sheep.

PMID- 14975925
TI  - Angiotensin II mediates uterine vasoconstriction through alpha-stimulation.
AB  - Intravenous angiotensin II (ANG II) increases uterine vascular resistance (UVR),
      whereas uterine intra-arterial infusions do not. Type 2 ANG II (AT(2)) receptors
      predominate in uterine vascular smooth muscle; this may reflect involvement of
      systemic type 1 ANG II (AT(1)) receptor-mediated alpha-adrenergic activation. To
      examine this, we compared systemic pressor and UVR responses to intravenous
      phenylephrine and ANG II without and with systemic or uterine alpha-receptor
      blockade and in the absence or presence of AT(1) receptor blockade in pregnant
      and nonpregnant ewes. Systemic alpha-receptor blockade inhibited phenylephrine
      mediated increases in mean arterial pressure (MAP) and UVR, whereas uterine alpha
      receptor blockade alone did not alter pressor responses and resulted in
      proportionate increases in UVR and MAP. Although neither systemic nor uterine
      alpha-receptor blockade affected ANG II-mediated pressor responses, UVR responses
      decreased >65% and also were proportionate to increases in MAP. Systemic AT(1)
      receptor blockade inhibited all responses to intravenous ANG II. In contrast,
      uterine AT(1) receptor blockade + systemic alpha-receptor blockade resulted in
      persistent proportionate increases in MAP and UVR. Uterine AT(2) receptor
      blockade had no effects. We have shown that ANG II-mediated pressor responses
      reflect activation of systemic vascular AT(1) receptors, whereas increases in UVR
      reflect AT(1) receptor-mediated release of an alpha-agonist and uterine
      autoregulatory responses.

PMID- 14975926
TI  - PKC-epsilon regulation of extracellular signal-regulated kinase: a potential role
      in phenylephrine-induced cardiocyte growth.
AB  - Hypertrophic growth of cardiac muscle is dependent on activation of the PKC
      epsilon isoform. To define the effectors of PKC-epsilon involved in growth
      regulation, recombinant adenoviruses were used to overexpress either wild-type
      PKC-epsilon (PKC-epsilon/WT) or dominant negative PKC-epsilon (PKC-epsilon/DN) in
      neonatal rat cardiocytes. PKC-epsilon/DN inhibited acute activation of PKC
      epsilon produced in response to phorbol ester and reduced ERK1/2 activity as
      measured by the phosphorylation of p42 and p44 isoforms. The inhibitory effects
      were specific to PKC-epsilon because PKC-epsilon/DN did not prevent translocation
      of either PKC-alpha or PKC-delta. Overexpression of PKC-epsilon/DN blunted the
      acute increase in ERK1/2 phorphorylation induced by the alpha(1)-adrenergic
      agonist phenylephrine (PE ). Inhibition of PKC-delta with rottlerin potentiated
      the effects of PE on ERK1/2 phosphorylation. PKC-epsilon/DN adenovirus also
      blocked cardiocyte growth as measured after 48 h of PE treatment, although the
      multiplicity of infection was lower than that required to block acute ERK1/2
      activation. PE activated p38 mitogen-activated protein kinase as measured by its
      phosphorylation, but the response was not blocked by PKC inhibitors or by
      overexpression of PKC-epsilon/DN. Taken together, these studies show that the
      hypertrophic agonist PE regulates ERK1/2 activity in cardiocytes by a pathway
      dependent on PKC-epsilon and that PE-induced growth is mediated by PKC-epsilon.

PMID- 14975927
TI  - Cyclopiazonic acid decreases spontaneous transient depolarizations in guinea pig
      mesenteric lymphatic vessels in endothelium-dependent and -independent manners.
AB  - Guinea pig mesenteric lymphatic vessels exhibit vasomotion through a pacemaker
      mechanism that involves intracellular Ca(2+) release and resultant spontaneous
      transient depolarizations (STDs) of the smooth muscle membrane potential. This
      study presents a detailed characterization of the effects of cyclopiazonic acid
      (CPA) on this pacemaker activity. Microelectrode recordings from smooth muscle in
      vessel segments revealed that application of CPA (1-10 microM) caused a
      hyperpolarization accompanied by a decrease in the frequency and amplitude of
      STDs. The CPA-induced hyperpolarization was abolished after destruction of the
      endothelium and in the presence of N(G)-nitro-L-arginine (100 microM) or 1H
      [1,2,4]oxadiazolol-[4,3-a]quinoxaline-1-one (10 microM), which suggests a
      contribution of endothelium-derived nitric oxide (EDNO) in this response. In the
      absence of EDNO-induced effects, CPA decreased the frequency and amplitude of
      STDs recorded before and in the presence of the thromboxane A(2) mimetic U-46619,
      norepinephrine, or thimerosal. CPA abolished U-46619-induced vasomotion as
      determined by measurement of constriction-associated intracellular Ca2+
      concentration using the ratiometric Ca2+ indicator fura-2. The endothelial
      actions of CPA were compared with those of ACh, which is known to cause EDNO
      release in this preparation. Although CPA and ACh both increased endothelial
      intracellular Ca2+ concentration and depolarized the membrane potential, the
      kinetics of action for both parameters were markedly slower for CPA than ACh.
      These results suggest that CPA first hyperpolarizes the lymphatic smooth muscle
      and decreases STD frequency and amplitude through endothelial release of EDNO,
      and second, consistent with the action of CPA to inhibit sarcoplasmic reticulum
      Ca2+-ATPase and deplete Ca2+ stores, it further reduces STD activity. Inhibition
      of the lymphatic smooth muscle pacemaker mechanism is thought to abolish agonist
      induced vasomotion.

PMID- 14975928
TI  - Molecular and functional characterization of common polymorphisms in HERG (KCNH2)
      potassium channels.
AB  - Long QT syndrome (LQTS) is a cardiac repolarization disorder that can lead to
      arrhythmias and sudden death. Chromosome 7-linked inherited LQTS (LQT2) is caused
      by mutations in human ether-a-go-go-related gene (HERG; KCNH2), whereas drug
      induced LQTS is caused primarily by HERG channel block. Many common polymorphisms
      are functionally silent and have been traditionally regarded as benign and
      without physiological consequence. However, the identification of common
      nonsynonymous single nucleotide polymorphisms (nSNPs; i.e., amino-acid coding
      variants) with functional phenotypes in the SCN5A Na(+) channel and MiRP1 K(+)
      channel beta-subunit have challenged this viewpoint. In this report, we test the
      hypothesis that common missense HERG polymorphisms alter channel physiology.
      Comprehensive mutational analysis of HERG was performed on genomic DNA derived
      from a population-based cohort of sudden infant death syndrome and two reference
      allele cohorts derived from 100 African American and 100 Caucasian individuals.
      Amino acid-encoding variants were considered common polymorphisms if they were
      present in at least two of the three study cohorts with an allelic frequency
      >0.5%. Four nSNPs were identified: K897T, P967L, R1047L, and Q1068R. Wild-type
      (WT) and polymorphic channels were heterologously expressed in human embryonic
      kidney cells, and biochemical and voltage-clamp techniques were used to
      characterize their functional properties. All channel types were processed
      similarly, but several electrophysiological differences were identified: 1) K897T
      current density was lower than the other polymorphic channels; 2) K897T channels
      activated at more negative potentials than WT and R1047L; 3) K897T and Q1068R
      channels inactivated and recovered from inactivation faster than WT, P967L, and
      R1047L channels; and 4) K897T channels showed subtle differences compared with WT
      channels when stimulated with an action potential waveform. In contrast to K897T
      and Q1068R channels, P967L and R1047L channels were electrophysiologically
      indistinguishable from WT channels. All HERG channels had similar sensitivity to
      block by cisapride. Therefore, some HERG polymorphic channels are
      electrophysiologically different from WT channels.

PMID- 14975929
TI  - Effects of specific signal transduction inhibitors on increased permeability
      across rat endothelial monolayers induced by neuropeptide Y or VEGF.
AB  - Neuropeptide Y (NPY) elevates the permeability of cultured rat aortic endothelial
      cells (RAECs) in monolayer cultures under hypoxic conditions (5% O(2)) possibly
      by binding to the NPY Y(3) receptor. The present study evaluated the effects of
      NPY compared to vascular endothelial growth factor (VEGF). RAECs were cultured on
      the upper chamber base of a double-chamber culture system, FITC-labeled albumin
      was introduced into the chamber, and permeation into the lower chamber was
      measured. Treatment was with 3 x 10(-7) M NPY or 10(-7) g/ml VEGF for 2 h along
      with specific inhibitors. The VEGF receptor-2 tyrosine kinase inhibitor
      tyrphostin SU-1498 and the protein kinase C inhibitor bis-indolylmaleimide I (GF
      109203X) suppressed the VEGF-induced increase in monolayer permeability but not
      that caused by NPY. Furthermore, although the action of NPY was blocked in a
      concentration-dependent manner by phospholipase C inhibitor 1-(6-[[(17beta)-3
      methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl)-1H-pyrrole-2,5-dione (U-73122),
      it was less sensitive than VEGF. However, the effects of both NPY and VEGF on the
      permeability of the RAEC monolayer were blocked with equal concentration
      dependence by STI571 (imatinib mesylate), which is an inhibitor of Abl tyrosine
      kinase in the nucleus and/or cytoplasm. The myosin light-chain kinase inhibitor 1
      (5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine HCl (ML-9) suppressed
      both NPY- and VEGF-induced increment in permeability by approximately 70%,
      whereas the calmodulin-dependent kinase inhibitor DY-9760e could decrease to
      below the baseline. These results indicate that the NPY Y(3)-receptor subtype is
      specifically linked to the effects of STI571 on endothelial cells, and that NPY,
      a sympathetic coneurotransmitter, may increase vascular permeability in
      association with altered intracellular or nuclear signal transduction.

PMID- 14975930
TI  - Antioxidant-independent ascorbate enhancement of catecholamine-induced
      contractions of vascular smooth muscle.
AB  - Ascorbate reduces the oxidation rate of catecholamines and, by an independent
      mechanism, enhances rabbit aortic ring contractions initiated by catecholamines.
      The largest significantly different fractional increases in force produced by
      ascorbate enhancement of norepinephrine (NE), epinephrine, phenylpropanolamine
      (PPA), and ephedrine (Eph) are 5.5, 1.8, 1.6, and 1.3 times, respectively. In
      physiological salt solutions bubbled with 95% O(2) at 37 degrees C, NE, PPA, and
      Eph have oxidation rate constants of 1.24, 247, and 643 h, respectively.
      Ascorbate significantly enhances 100 nM NE contractions by at least twofold at
      all ascorbate concentrations >15 microM, including the entire physiological range
      of 40-100 microM. Ascorbate preloading and washout followed by NE exposure
      produces significantly greater contractions than NE without ascorbate preloading
      but significantly lower than NE simultaneously with ascorbate. Ascorbate does not
      enhance K(+)- or angiotensin II-induced contractions. Ascorbate enhancement of
      catecholamine contractions occurs in addition to the reduction in oxidation rate,
      because the increases in force occur faster than oxidation can occur, the
      increases occur with compounds that have negligible oxidation rates, and the
      increases occur when ascorbate and NE are not physically present together. These
      results are consistent with ascorbate acting on the adrenergic receptor.
      Ascorbate may play a role in shock and asthma treatments and potentiate the
      cardiovascular health consequences of PPA and Eph (Ephedra).

PMID- 14975931
TI  - Augmentation of moxonidine-induced increase in ANP release by atrial hypertrophy.
AB  - Imidazoline receptors are divided into I(1) and I(2) subtypes. I(1)-imidazoline
      receptors are distributed in the heart and are upregulated during hypertension or
      heart failure. The aim of this study was to define the possible role of I(1)
      imidazoline receptors in the regulation of atrial natriuretic peptide (ANP)
      release in hypertrophied atria. Experiments were performed on isolated, perfused,
      hypertrophied atria from remnant-kidney hypertensive rats. The relatively
      selective I(1)-imidazoline receptor agonist moxonidine caused a decrease in pulse
      pressure. Moxonidine (3, 10, and 30 micromol/l) also caused dose-dependent
      increases in ANP secretion, but clonidine (an alpha(2)-adrenoceptor agonist) did
      not. Pretreatment with efaroxan (a selective I(1)-imidazoline receptor
      antagonist) or rauwolscine (a selective alpha(2)-adrenoceptor antagonist)
      inhibited the moxonidine-induced increases in ANP secretion and interstitial ANP
      concentration and decrease in pulse pressure. However, the antagonistic effect of
      efaroxan on moxonidine-induced ANP secretion was greater than that of
      rauwolscine. Neither efaroxan nor rauwolscine alone has any significant effects
      on ANP secretion and pulse pressure. In hypertrophied atria, the moxonidine
      induced increase in ANP secretion and decrease in pulse pressure were markedly
      augmented compared with nonhypertrophied atria, and the relative change in ANP
      secretion by moxonidine was positively correlated to atrial hypertrophy. The
      accentuation by moxonidine of ANP secretion was attenuated by efaroxan but not by
      rauwolscine. These results show that moxonidine increases ANP release through
      (preferentially) the activation of atrial I(1)-imidazoline receptors and also via
      different mechanisms from clonidine, and this effect is augmented in
      hypertrophied atria. Therefore, we suggest that cardiac I(1)-imidazoline
      receptors play an important role in the regulation of blood pressure.

PMID- 14975932
TI  - Microvascular pressure and functional capillary density in extreme hemodilution
      with low- and high-viscosity dextran and a low-viscosity Hb-based O2 carrier.
AB  - Blood losses are usually corrected initially by the restitution of volume with
      plasma expanders and subsequently by the restoration of oxygen-carrying capacity
      using either a blood transfusion or possibly, in the near future, oxygen-carrying
      plasma expanders. The present study was carried out to test the hypothesis that
      high-plasma viscosity hemodilution maintains perfused functional capillary
      density (FCD) by preserving capillary pressure. Microvascular pressure responses
      to extreme hemodilution with low- (LV) and high-viscosity (HV) plasma expanders
      and an exchange transfusion with a polymerized bovine cell-free Hb (PBH) solution
      were analyzed in the awake hamster window chamber model (n = 26). Systemic
      hematocrit was reduced from 50% to 11%. PBH produced a greater mean arterial
      blood pressure than the nonoxygen carriers. FCD was higher after a HV plasma
      expander (70 +/- 15%) vs. PBH (47 +/- 12%). Microvascular pressure spanning the
      capillary network was higher after a HV plasma expander (16-19 mmHg) compared
      with PBH (12-16 mmHg) and a LV plasma expander (11-14 mmHg) but lower than
      control (22-26 mmHg). FCD was found to be directly proportional to capillary
      pressure. The use of a HV plasma expander in extreme hemodilution maintained the
      number of perfused capillaries and tissue perfusion by comparison with a LV
      plasma expander due to increased mean arterial blood pressure and capillary
      pressure. The use of PBH increased mean arterial pressure but reduced capillary
      pressure due to vasoconstriction and did not maintain FCD.

PMID- 14975933
TI  - Caspase-dependent cytochrome c release and cell death in chick cardiomyocytes
      after simulated ischemia-reperfusion.
AB  - We recently demonstrated that reperfusion rapidly induces the mitochondrial
      pathway of apoptosis in chick cardiomyocytes after 1 h of simulated ischemia.
      Here we tested whether ischemia-reperfusion (I/R)-induced apoptosis could be
      initiated by caspase-dependent cytochrome c release in this model of
      cardiomyocyte injury. Fluorometric assays of caspase activity showed little, if
      any, activation of caspases above baseline levels induced by 1 h of ischemia
      alone. However, these assays revealed rapid activation of caspase-2, yielding a
      2.95 +/- 0.52-fold increase (over ischemia only) within the 1st h of reperfusion,
      whereas activities of caspases-3, -8, and -9 increased only slightly from their
      baseline levels. The rapid and prominent activation of caspase-2 suggested that
      it could be an important initiator caspase in this model, and using specific
      caspase inhibitors given only at the point of reperfusion, we tested this
      hypothesis. The caspase-2 inhibitor benzyloxycarbonyl-Val-Asp(Ome)-Val-Ala
      Asp(Ome)-CH(2)F was the only caspase inhibitor that significantly inhibited
      cytochrome c release from mitochondria. This inhibitor also completely blocked
      activation of caspases-3, -8, and -9. The caspase-3/7 inhibitor transiently and
      only partially blocked caspase-2 activity and was less effective in blocking the
      activities of caspases-8 and -9. The caspase-8 inhibitor failed to significantly
      block caspase-2 or -3, and the caspase-9 inhibitor blocked only caspase-9.
      Furthermore, the caspase-2 inhibitor protected against I/R-induced cell death,
      but the caspase-8 inhibitor failed to do so. These data suggest that active
      caspase-2 initiates cytochrome c release after reperfusion and that it is
      critical for the I/R-induced apoptosis in this model.

PMID- 14975934
TI  - Gender differences in myogenic tone in superoxide dismutase knockout mouse:
      animal model of oxidative stress.
AB  - Oxidative stress mediated by prooxidants has been implicated in the pathogenesis
      of vascular disorders. However, the effect of prooxidants on myogenic regulation
      of vascular function and the differential influence of gender is not known. SOD,
      an intracellular enzyme, restricts excess prooxidant levels and may limit
      vascular dysfunction. We therefore tested the effects of Cu,Zn SOD deficiency on
      vascular tone in both male and female SOD knockout (SOD-/-) mice. We hypothesized
      that myogenic tone would be enhanced in SOD-/- mice by excess prooxidants
      compared with wild-type control mice. Indeed, resistance-sized mesenteric
      arteries from SOD-/- mice exhibited enhanced myogenic tone compared with control
      mice. Myogenic tone was lower in female than male control mice. Interestingly,
      this gender effect was absent in SOD-/- mice, such that myogenic tone of
      mesenteric arteries from females was equated to that of arteries from males.
      Furthermore, the pathways that modulate myogenic tone were diverse. In both male
      and female control mice, inhibition of prostaglandin H synthase (PGHS) and nitric
      oxide synthase (NOS) pathways enhanced myogenic tone. In female SOD-/- mice,
      inhibition of PGHS and NOS pathways enhanced myogenic tone to a greater extent
      compared with control mice. Conversely, in male SOD-/- mice, NOS and PGHS
      inhibition did not alter tone and only inhibition of gap junctions enhanced
      myogenic tone. In conclusion, this study revealed enhanced myogenic tone in SOD-/
      mice compared with control mice. Furthermore, Cu,Zn SOD deficiency particularly
      enhanced myogenic tone in female mice such that their vascular tone attained the
      level of male SOD-/- mice, possibly mediated by prooxidants.

PMID- 14975935
TI  - Glycosaminoglycan polymerization may enable osmotically inactive Na+ storage in
      the skin.
AB  - Osmotically inactive skin Na(+) storage is characterized by Na(+) accumulation
      without water accumulation in the skin. Negatively charged glycosaminoglycans
      (GAGs) may be important in skin Na(+) storage. We investigated changes in skin
      GAG content and key enzymes of GAG chain polymerization during osmotically
      inactive skin Na(+) storage. Female Sprague-Dawley rats were fed a 0.1% or 8%
      NaCl diet for 8 wk. Skin GAG content was measured by Western blot analysis. mRNA
      content of key dermatan sulfate polymerization enzymes was measured by real-time
      PCR. The Na(+) concentration in skin was determined by dry ashing. Skin Na(+)
      concentration during osmotically inactive Na(+) storage was 180-190 mmol/l.
      Increasing skin Na(+) coincided with increasing GAG content in cartilage and
      skin. Dietary NaCl loading coincided with increased chondroitin synthase mRNA
      content in the skin, whereas xylosyl transferase, biglycan, and decorin content
      were unchanged. We conclude that osmotically inactive skin Na(+) storage is an
      active process characterized by an increased GAG content in the reservoir tissue.
      Inhibition or disinhibition of GAG chain polymerization may regulate osmotically
      inactive Na(+) storage.

PMID- 14975936
TI  - Ozone-induced acute pulmonary injury in inbred mouse strains.
AB  - To determine if host factors influence the time course and extent of lung injury
      after acute inhalation of ozone (O3), we evaluated the physiologic and biologic
      response of nine genetically diverse inbred strains of mice (C57BL/6J, 129/SvIm,
      BTBR, BALB/cJ, DBA/2J, A/J, FVB/NJ, CAST/Ei, and C3H/HeJ) exposed to O3 (2.0 ppm
      x 3 h). Whole lung lavage determined that 129/Svlm, BTBR, DBA/2J, and FVB/NJ had
      a peak increase in polymorphonuclear cells (PMNs) at 6 h, whereas C57BL/6J and
      CAST/Ei had a peak increase at 24 h after exposure; airway PMNs were minimally
      elevated in A/J and C3H/HeJ; BALB/cJ had a predominant lymphocytic influx.
      Interleukin-6 concentration in the lavage fluid was associated with the influx of
      PMNs, whereas the total protein in the lavage fluid did not always correlate with
      lavage cellularity. Respiratory responses were monitored using whole body
      plethysmography and enhanced pause index. C57BL/6J, BALB/cJ, 129/SvIm, and BTBR
      were highly sensitive to O3 and exhibited significant increases in enhanced pause
      to methacholine aerosol stimulation at 6 and 24 h after exposure to O3. In
      contrast, DBA/2J, A/J, FVB/NJ, CAST/Ei, and C3H/HeJ strains had demonstrated
      increases in sensitivity to MCh at 6 h after exposure, but responses had returned
      to near baseline by 24 h after exposure to O3. Epithelial cell proliferation as
      assessed by proliferating cell nuclear antigen staining was evident at 24 h after
      exposure to O3. C57BL/6J and A/J showed 4% proliferating cell nuclear antigen
      positive cells; 129/SvIm, DBA/2J, and FVB/NJ had 1-3%; and BTBR, BALB/cJ,
      CAST/Ei, and C3H/HeJ had < 1%. Phenotypic measurements in six inbred strains were
      used for an in silico genome analysis based on the Roche mouse database.
      Consistent loci on chromosomes 1, 7, and 15 were among those identified to have a
      significant association with the phenotypes studied. In aggregate, our approach
      has identified O3-resistant (C3H/HeJ and A/J) and -vulnerable (C57BL/6J and
      129/SvIm) strains of mice, and determined novel genomic loci, suggesting a clear
      genetic basis for the lung response to inhaled O3.

PMID- 14975937
TI  - Fibroblast growth factor-10 attenuates H2O2-induced alveolar epithelial cell DNA
      damage: role of MAPK activation and DNA repair.
AB  - Fibroblast growth factor-10 (FGF-10), an alveolar epithelial cell (AEC) mitogen
      that is critical for lung development, may promote AEC repair. We determined
      whether FGF-10 attenuates H2O2-induced, A549 and rat alveolar type II cell DNA
      damage. We show that FGF-10 prevents H2O2-induced DNA damage assessed by an
      alkaline elution, ethidium bromide fluorescence as well as by a comet assay.
      Mitogen-activated protein kinase inhibitors abolished the protective effect of
      FGF-10 against H2O2-induced DNA damage yet had no effect on H2O2-induced DNA
      damage. A Grb2-SOS inhibitor (SH3 binding peptide), an Ras inhibitor (farnesyl
      transferase inhibitor 277), and an Raf-1 inhibitor (forskolin) each prevented FGF
      10- and H2O2-induced A549 cell ERK1/2 phosphorylation. Also, FGF-10 and H2O2 each
      induced negligible ERK1/2 phosphorylation in Ras dominant-negative (N17) cells.
      Inhibitors of Ras and Raf-1 blocked the protective effect of FGF-10 against H2O2
      induced DNA damage but had no effect on H2O2-induced DNA damage. Furthermore,
      cold conditions and aphidicolin, an inhibitor of DNA polymerase-alpha, -delta,
      and -epsilon, each blocked the protective effects of FGF-10, suggesting a role
      for DNA repair. We conclude that FGF-10 attenuates H2O2-induced AEC DNA damage by
      mechanisms that involve activation of Grb2-SOS/Ras/RAF-1/ERK1/2 pathway and DNA
      repair.

PMID- 14975938
TI  - Proteomic analysis of exosomes isolated from human malignant pleural effusions.
AB  - Exosomes are membrane vesicles from endosomal origin secreted by various cells
      such as hematopoietic, epithelial, and tumor cells. Exosomes secreted by tumor
      cells contain specific antigens potentially useful for immunotherapeutic
      purposes. Our aim was to determine if exosomes are present in human cancerous
      pleural effusions and to identify their proteomic content. Exosomes were purified
      by sucrose gradient ultracentrifugation, and electron microscopy was used to
      check both concentration and purity of exosomes. Proteins were separated by one
      dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and
      protein bands were identified by matrix-assisted laser desorption ionization time
      of-flight mass spectrometry and Western blotting. Exosomes were present in
      pleural fluid obtained from patients suffering from mesothelioma (n = 4), lung
      cancer (n = 2), breast cancer (n = 2), and ovarian cancer (n = 1). As previously
      reported by others, antigen-presenting molecules, cytoskeletal proteins, and
      signal transduction-involved proteins were present. Proteins not previously
      reported were identified (SNX25, BTG1, PEDF, thrombospondin 2). Different types
      of immunoglobulins and complement factors were abundantly present in the sucrose
      fractions containing exosomes. Exosome-directed specificity of these
      immunoglobulins was not observed. In conclusion, sucrose gradient
      ultracentrifugation allows isolation of exosomes from malignant pleural
      effusions. However, pleural fluid proteins and especially immunoglobulins are
      coisolated and may hamper the use of exosomes isolated from malignant effusion
      for immunotherapy programs.

PMID- 14975939
TI  - Mechanical strain inhibits airway smooth muscle gene transcription via protein
      kinase C signaling.
AB  - Mechanical strain affects airway myocyte phenotype, cytoskeletal architecture,
      proliferation, and contractile function. We hypothesized that (i) short-term
      mechanical strain modulates transcription of smooth muscle-specific gene
      promoters for SM22 and smooth muscle myosin heavy chain (smMHC); and (ii) strain
      induced change is mediated by altered actin polymerization in association with
      activation of protein kinase C (PKC). Primary cultured canine tracheal myocytes
      were transiently transfected with luciferase reporter plasmids harboring a murine
      SM22, human smMHC, or artificial serum response factor (SRF)-specific gene
      promoter and then subjected to cyclic strain for 48 h. This strain protocol
      significantly reduced transcriptional activity of SM22 and smMHC promoters and an
      artificial SRF-dependent promoter by 55 +/- 5.9%, 57 +/- 6.4%, and 75 +/- 7.9%,
      respectively, with concomitant reduction in F/G actin ratio by 31 +/- 8%. PKC
      inhibitors, GF109203X or Go6976, significantly attenuated these affects. Similar
      to strain, strain-independent activation of PKC inhibited SM22, smMHC, and SRF
      dependent promoter activity by 61 +/- 4%, 66 +/- 5%, and 28 +/- 15%,
      respectively, and reduced the F/G actin ratio by 30 +/- 5%. Gel shift assay
      revealed that PKC activation led to decreased binding of the required
      transcription factor, SRF, to CArG elements in the SM22 promoter. These data
      suggest a previously unknown role for PKC isoforms in mechanosensitive signaling
      in airway myocytes that is associated with coordinated regulation of actin
      cytoskeletal dynamics and smooth muscle-specific gene transcription.

PMID- 14975940
TI  - Characterization of the effect of interleukin-10 on silica-induced lung fibrosis
      in mice.
AB  - We previously described a reduction of silica-induced lung fibrosis in
      interleukin-10-deficient mice (IL-10-/-) (Huaux and colleagues; Am. J. Respir.
      Cell Mol. Biol. 1998;18:51-59). In the present study, we further dissect the
      exact functions of IL-10 in experimental silicosis. The reduced lung fibrotic
      response to silica in IL-10-/- mice was accompanied by a marked recruitment of
      TH1 CD4+ lymphocytes. However, treatment with anti-CD4 antibodies reduced silica
      induced lung fibrosis in both IL-10-/- and IL-10+/+ mice, suggesting that this T
      cell population actually contributes to the extension of the fibrotic lesions in
      a manner that is independent of IL-10. In IL-10-/- mice, silica-induced lung
      production of the profibrotic mediator transforming growth factor (TGF)-beta1 and
      the antifibrotic eicosanoid PGE2 were reduced and increased, respectively,
      relative to that in IL-10+/+ mice. In addition, in vitro experiments indicated
      that recombinant IL-10 upregulated TGF-beta1 expression in alveolar macrophages
      while in contrast it downregulated PGE2 production and cyclooxygenase-2
      expression in both lung fibroblasts and macrophages. Thus the net profibrotic
      activity of IL-10 in vivo appears to be mediated by its ability to stimulate the
      expression of the profibrotic cytokine TGF-beta1 while suppressing the expression
      of cyclooxygenase-2 and thus production of the antifibrotic eicosanoid PGE2.
      These effects appear to be independent of the enhanced lung CD4+ T-lymphocytosis
      observed in IL-10-deficient mice.

PMID- 14975941
TI  - Role of interleukin-5 and eosinophils in allergen-induced airway remodeling in
      mice.
AB  - Asthma is a chronic inflammatory disease characterized by variable bronchial
      obstruction, hyperresponsiveness, and by tissue damage known as airway
      remodeling. In the present study we demonstrate that interleukin (IL)-5 plays an
      obligatory role in the airway remodeling observed in experimental asthma. BALB/c
      mice sensitized by intraperitoneal injections of ovalbumin and exposed daily to
      aerosol of ovalbumin for up to 3 wk, develop eosinophilic infiltration of the
      bronchi and subepithelial and peribronchial fibrosis. The lesions are associated
      with increased amounts of hydroxyproline in the lungs and elevated levels of
      eosinophils and transforming growth factor (TGF)-beta1 in the bronchoalveolar
      lavage fluid. After 1 wk of allergen challenge, TGF-beta is mainly produced by
      eosinophils accumulated in the peribronchial and perivascular lesions. At a later
      stage of the disease, the main source of TGF-beta is myofibroblasts, identified
      by alpha-smooth muscle actin mAb. We show that all these lesions, including
      fibrosis, are abolished in sensitized and allergen-exposed IL-5 receptor-null
      mice, whereas they are markedly accentuated in IL-5 transgenic animals. More
      importantly, treatment of wild-type mice with neutralizing anti-IL-5 antibody,
      administered before each allergen challenge, almost completely prevented
      subepithelial and peribronchial fibrosis. These findings demonstrated that
      eosinophils are involved in allergen-induced subepithelial and peribronchial
      fibrosis probably by producing a fibrogenic factor, TGF-beta1.

PMID- 14975942
TI  - Beryllium-induced tumor necrosis factor-alpha production by CD4+ T cells is
      mediated by HLA-DP.
AB  - Beryllium (Be) presentation to CD4+ T cells from patients with chronic beryllium
      disease (CBD) results in T cell activation, and these Be-specific CD4+ T cells
      undergo clonal proliferation and T-helper 1-type cytokine production. In exposed
      workers, genetic susceptibility to this granulomatous disorder is associated with
      particular HLA-DPB1 alleles. We hypothesized that these HLA-DP molecules could
      mediate Be-stimulated tumor necrosis factor-alpha (TNF-alpha) messenger RNA
      (mRNA) and protein production. Using intracellular cytokine staining, we found
      that treatment with an anti-HLA-DP, but not anti-HLA-DR, monoclonal antibody
      inhibited Be-stimulated TNF-alpha expression in lung CD3+ CD4+ T cells. This
      monoclonal antibody also blocked Be-specific T cell proliferation, increased
      production of TNF-alpha mature-mRNA transcripts, and increased TNF-alpha protein
      production by Be-stimulated CBD peripheral blood mononuclear cells and
      bronchoalveolar lavage (BAL) cells. The Be-stimulated upregulation of TNF-alpha
      mature-mRNA levels with TNF-alpha protein production was a unique property of CBD
      BAL cells, and did not occur in BAL cells from Be-sensitized patients without
      CBD, or sarcoidosis BAL cells. This study identifies HLA-DP as a regulatory
      component in the activation of T cell receptors on Be-specific CD4+ T cells from
      CBD patients resulting in proliferation and proinflammatory cytokine production.

PMID- 14975944
TI  - Small renal cell carcinomas: correlation of size with tumor stage, nuclear grade,
      and histologic subtype.
AB  - OBJECTIVE: Our goal was to correlate the size of renal cell carcinoma with tumor
      stage, nuclear grade, and histologic subtype in patients treated using partial or
      radical nephrectomy. MATERIALS AND METHODS: We retrospectively reviewed 213
      consecutive renal cell carcinomas resected at our institution from 1995 through
      1999. Three groups of lesions stratified by size (< or = 3 cm, > 3-5 cm, > 5 cm)
      were compared with regard to pathologic findings. Statistical significance was
      assessed using Fisher's exact test. RESULTS: Of 50 lesions 3 cm or smaller, 19
      (38%) had extension outside the renal capsule (T3 or T4) and 14 (28%) were a high
      nuclear grade (Fuhrman grade 3 or 4). Lesions 3 cm or smaller and those greater
      than 3 cm to 5 cm did not differ statistically with regard to T stage or nuclear
      grade. Lesions larger than 5 cm showed a statistically higher T stage (p < 0.001)
      and nuclear grade (p = 0.001) than the other smaller lesions. More non-clear cell
      tumors were found in the two groups of smaller lesions (p = 0.105) but without
      statistical significance. The majority (58%) of the tumors were asymptomatic and
      had been detected incidentally on cross-sectional imaging. Lesions larger than 5
      cm were significantly more likely to be symptomatic (p < 0.001). Seventy-nine
      percent of the tumors 3 cm or smaller were incidental, and these lesions did not
      differ significantly from the symptomatic lesions with regard to stage, grade, or
      histology. CONCLUSION: In our study population, renal cell carcinomas up to 3 cm,
      including asymptomatic lesions, showed a significant incidence of high nuclear
      grade and tumor extension beyond the renal capsule; these findings support
      aggressive management of small lesions. Symptomatic status was not an adequate
      discriminator to guide management. A longitudinal study is necessary to further
      evaluate the efficacy of current patterns of therapy.

PMID- 14975946
TI  - Carcinoid tumors of the small bowel: a multitechnique imaging approach.

PMID- 14975947
TI  - Prognostic value of CT in the early assessment of patients with acute
      pancreatitis.
AB  - OBJECTIVE: This study investigates the prognostic value of early CT in acute
      pancreatitis, the role of pancreatic necrosis as a indicator of prognosis, and
      the need for the routine use of IV iodinated contrast material in early CT to
      assess prognosis in these patients. MATERIALS AND METHODS: We conducted a
      retrospective review of 148 patients who underwent unenhanced and contrast
      enhanced helical CT within 72 hr after onset of symptoms of a first episode of
      acute pancreatitis. Patients were classified by CT grade and grouped into two
      categories (mild: grades A, B, C; and severe: grades D and E) that were
      correlated with complications and death. In the grades including patients with
      pancreatic necrosis, it was also correlated with complications and death.
      RESULTS: All complications (n = 15) and deaths (n = 4) occurred in patients with
      a CT grade of severe disease; differences as compared with mild grade were
      significant (p < 0.001 and p < 0.03, respectively). CT grade had a sensitivity
      and specificity of 100% and 61.6%, respectively, for predicting morbidity and
      100% and 56.9% for predicting mortality. The 13 patients with necrosis were all
      in the severe group (p < 0.001). Necrosis detection on early CT had a sensitivity
      and specificity of 53.3% and 90.2%, respectively, for predicting morbidity and
      75% and 83.8% for mortality. CONCLUSION: Early unenhanced CT alone was a good
      indicator of severity of acute pancreatitis in our selected population. CT grade
      was sensitive for predicting outcome in acute pancreatitis. Pancreatic necrosis,
      estimated on early, contrast-enhanced CT and seen only in patients having severe
      disease, was a specific predictor of morbidity and mortality. These findings lead
      us to suggest that the use of iodinated contrast material to assess necrosis can
      be reserved for only those patients classified as having severe disease on
      unenhanced CT.

PMID- 14975948
TI  - Medical radionuclide supplies and national policy: time for a change?

PMID- 14975949
TI  - Computer-aided detection schemes: the effect of limiting the number of cued
      regions in each case.
AB  - OBJECTIVE: We assessed performance changes of a mammographic computer-aided
      detection scheme when we restricted the maximum number of regions that could be
      identified (cued) as showing positive findings in each case. MATERIALS AND
      METHODS: A computer-aided detection scheme was applied to 500 cases (or 2,000
      images), including 300 cases in which mammograms showed verified malignant
      masses. We evaluated the overall case-based performance of the scheme using a
      free-response receiver operating characteristic approach, and we measured
      detection sensitivity at a fixed false-positive detection rate of 0.4 per image
      after gradually reducing the maximum number of cued regions allowed for each case
      from seven to one. RESULTS: The original computer-aided detection scheme achieved
      a maximum case-based sensitivity of 97% at 3.3 false-positive detected regions
      per image. For a detection decision score set at 0.565, the scheme had a 79%
      (237/300) case-based sensitivity, with 0.4 false-positive detected regions per
      image. After limiting the number of maximum allowed cued regions per case, the
      false-positive rates decreased faster than the true-positive rates. At a maximum
      of two cued regions per case, the false-positive rate decreased from 0.4 to 0.21
      per image, whereas detection sensitivity decreased from 237 to 220 masses. To
      maintain sensitivity at 79%, we reduced the detection decision score to as low as
      0.36, which resulted in a reduction of false-positive detected regions from 0.4
      to 0.3 per image and a reduction in region-based sensitivity from 66.1% to 61.4%.
      CONCLUSION: Limiting the maximum number of cued regions per case can improve the
      overall case-based performance of computer-aided detection schemes in
      mammography.

PMID- 14975950
TI  - Rewarding authors in a digital era: assigning academic credit for contributions
      to digital articles, web sites, teaching files, and lectures.

PMID- 14975951
TI  - Value of fat suppression in the MRI evaluation of suspected arrhythmogenic right
      ventricular dysplasia.
AB  - OBJECTIVE: Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by
      intramyocardial fibrofatty change. Fat suppression performed during conventional
      spin-echo imaging has been used to confirm fatty infiltration. The utility of fat
      suppression for enhancing the interpretation of studies of suspected ARVD has not
      previously been formally tested. We investigated the value of fat suppression for
      enhancing the interpretation of intramyocardial fatty infiltration. MATERIALS AND
      METHODS: Twenty-six consecutive patients clinically referred for evaluation of
      possible ARVD underwent cardiac MRI. Two independent observers reviewed the
      images retrospectively. Intramyocardial areas (n = 101) that had increased signal
      intensity relative to normal surrounding myocardium on T1-weighted conventional
      spin-echo images ("index areas") were identified. The index areas were
      interpreted for presence of fatty infiltration using two sets of images: The
      first set was obtained without fat suppression, and the second set was obtained
      with fat suppression. Agreement between reviewers and confidence of
      interpretation were determined and compared. RESULTS: Interobserver agreement was
      measured using a 5-point scale: 1, definitely not fat; 2, probably not fat; 3,
      equivocal; 4, probably fat; and 5, definitely fat. The resulting kappa values
      were 0.35 for non-fat-suppressed images and 0.55 for fat-suppressed images.
      Interobserver kappa increased from 0.67 without fat suppression to 0.90 with fat
      suppression using a 3-point scale: 1, not fat; 2, equivocal; and 3, fat.
      Confidence in the diagnosis increased from 7.2 without fat suppression to 8.8
      with fat suppression (p < 0.0001) on a 10-point scale ranging from 1, not
      confident, to 10, very confident. CONCLUSION: The use of fat-suppressed in
      addition to non-fat-suppressed conventional T1-weighted spin-echo imaging
      increased interobserver agreement and confidence in diagnosis and evaluation of
      intramyocardial fatty infiltration in patients who were suspected to have ARVD.

PMID- 14975953
TI  - Using MRI to assess aortic wall thickness in the multiethnic study of
      atherosclerosis: distribution by race, sex, and age.
AB  - OBJECTIVE: Understanding the determinants of subclinical atherosclerosis may aid
      in elucidating the pathogenesis of atherosclerosis and guide prevention
      strategies. In this pilot study, we investigated the role of aortic wall
      thickness as a measure of subclinical atherosclerosis, assessed a method by which
      to measure aortic wall thickness using MRI, and attempted to define differences
      in aortic wall thickness by patient race, sex, and age. SUBJECTS AND METHODS. In
      this prospective study, 196 participants (99 black, 97 white; 98 men, 98 women)
      were selected from the Multiethnic Study of Atherosclerosis, which consists of
      participants 45-84 years old without clinical cardiovascular disease, who were
      recruited from six study centers in the United States. We performed fast spin
      echo double inversion recovery MRI to measure thoracic aortic wall thickness. We
      tested interobserver agreement using the intraclass correlation coefficient, for
      sex and race differences in wall thickness using the Mann-Whitney test, and for
      associations between age and wall thickness using linear regression. RESULTS:
      Reproducibility was excellent for measurements of average and maximal wall
      thickness on MRI. Average and maximal wall thickness increased with age (p <
      0.001 and p = 0.002, respectively). Men had greater mean average wall thickness
      (2.32 vs 2.11 mm, p = 0.028) and mean maximal wall thickness (3.85 vs 3.31 mm, p
      = 0.010) than women. Blacks had greater mean maximal wall thickness than whites
      (3.74 vs 3.42 mm, p = 0.023). CONCLUSION: MRI is a feasible method to measure
      aortic wall thickness with high interobserver agreement. Aortic wall thickness
      increases with age and also varies by race and sex.

PMID- 14975954
TI  - MRI of atypical lipomatous hypertrophy of the interatrial septum.

PMID- 14975955
TI  - Noninvasive coronary imaging with MDCT in comparison to invasive conventional
      coronary angiography: a fast-developing technology.

PMID- 14975956
TI  - Use of inversion recovery contrast-enhanced MRI for cardiac imaging: spectrum of
      applications.

PMID- 14975957
TI  - Medicine in American art: The diagnosis.

PMID- 14975958
TI  - MDCT of a malignant anomalous right coronary artery.

PMID- 14975959
TI  - Detection of small pancreatic tumors with multiphasic helical CT.
AB  - OBJECTIVE: The purpose of this study was to evaluate the sensitivity and
      specificity of helical CT in the detection of adenocarcinomas of the pancreas
      measuring 2 cm or smaller at pathologic examination. MATERIALS AND METHODS: Thin
      section triple phase (20, 40, and 70 sec after the start of injection) contrast
      enhanced helical CT scans of the abdomen in 18 patients with a pancreatic
      carcinoma that was 2 cm or smaller and 18 patients with a normal pancreas were
      retrospectively reviewed by two senior radiologists who specialized in oncologic
      abdominal imaging. Discrepancies were resolved by consensus. The observers were
      unaware of the clinical information. CT scans were evaluated for the presence of
      a pancreatic mass, bile, and pancreatic duct stricture. The location and size of
      tumors as determined on CT were compared with pathologic findings. The CT results
      were also compared with the prospective CT interpretations derived from the
      radiology reports and with the endoscopic sonographic reports when available.
      RESULTS: The sensitivity of thin-section triple-phase helical CT in the detection
      of small pancreatic masses was 77%, and the specificity was 100% for the two
      experienced observers. The sensitivity and specificity were 72% and 100%,
      respectively, for the prospective interpretations done by 10 observers. There was
      no correlation between the tumor size at pathology and the CT measurements.
      CONCLUSION: Thin-section contrast-enhanced helical CT is sensitive and highly
      specific for the detection of pancreatic tumors measuring 2 cm or smaller.
      Improvement in the detection rate of this technique compared with previous
      techniques lies in the optimization of parenchymal enhancement during the
      pancreatic phase and the decrease in slice thickness.

PMID- 14975960
TI  - CT of Meckel's diverticulitis in 11 patients.
AB  - OBJECTIVE: This study reviews the CT findings of Meckel's diverticulitis in 11
      patients and, to our knowledge, represents the largest series of such cases
      reported to date. CONCLUSION: The inflamed Meckel's diverticulum may be
      visualized on CT in most patients, appearing as a blind-ending pouch of variable
      size and mural thickness and containing fluid, air, or particulate material with
      surrounding mesenteric inflammation. The location of the diverticulum may vary
      from the right lower quadrant to the mid abdomen, with most cases in this series
      located near midline. Optimal luminal opacification of the ileocecal bowel with
      oral contrast material facilitated detection of the diverticulum and also proved
      invaluable in enabling identification of the normal appendix. The diagnosis is
      most difficult in the setting of secondary intestinal obstruction.

PMID- 14975961
TI  - Extracolonic and incidental findings on CT colonography (virtual colonoscopy).
AB  - OBJECTIVE: The objective of our study was to prospectively determine the
      frequency and clinical importance of extracolonic findings on CT colonography in
      symptomatic patients. SUBJECTS AND METHODS. One hundred eleven symptomatic
      patients referred for colonoscopy underwent CT colonography before colonoscopy.
      Helical CT from the diaphragm to the symphysis was performed with the patient in
      the supine and prone positions after rectal air insufflation. Image
      interpretation was done on a digital workstation. Extracolonic findings were
      classified as minor, moderate, or major according to potential clinical
      importance. Patient records, with a follow-up time of about 3 years, were
      reviewed to determine final diagnoses. RESULTS: Twenty-six (23%) of the patients
      had CT findings of major importance such as lymphadenopathy (n = 7), aortic
      aneurysm (n = 6), suspected solid hepatic masses (n = 5), and suspected solid
      renal masses (n = 4). Fifty-eight patients (52%) had findings of moderate
      importance such as gallstones (n = 16), indeterminate renal masses (n = 9),
      adrenal masses with benign appearance (n = 8), and hiatal hernia (n = 7). Forty
      six patients (41%) had no or only minor findings, such as renal cysts (n = 34),
      renal calcifications (n = 19), and hepatic cysts (n = 14). Review of patient
      records showed that CT colonography contributed to the detection of major,
      previously unknown extracolonic disorders in 14 (13%) of the 111 patients.
      CONCLUSION: Potentially important extracolonic findings were revealed in 23% of
      the patients, leading to additional diagnostic or therapeutic considerations.
      Some of these findings were clinically important, whereas others were previously
      known or led to unnecessary workup. This finding must be taken into account when
      CT colonography is considered for routine diagnostic workup or screening.

PMID- 14975962
TI  - Abdominal cocoon: preoperative diagnostic clues from radiologic imaging with
      pathologic correlation.

PMID- 14975963
TI  - Triple-phase MDCT of hepatocellular carcinoma.
AB  - OBJECTIVE: The purpose of this study was to describe the appearances of
      hepatocellular carcinoma including intralesional contrast washout using a triple
      phase liver protocol on an MDCT scanner. MATERIALS AND METHODS: Fifty-one
      patients with newly diagnosed hepatocellular carcinoma underwent standardized
      triple-phase CT using a multidetector scanner. Pathologic proof was obtained in
      35 patients (69%); in 16 patients (31%), hepatocellular carcinoma was diagnosed
      on clinical and laboratory findings. Two radiologists independently reviewed the
      CT studies for the appearance and attenuation of the lesions. Intralesional
      washout of contrast material was evaluated subjectively and objectively.
      Statistical analysis was performed using Fisher's exact test to analyze the
      relationships between tumor appearance and alpha-fetoprotein level, tumor grade,
      and risk factor. Correlation between tumor size and appearance was analyzed using
      the Student's t test and Wilcoxon's rank sum test. RESULTS: The most common
      enhancement pattern for hepatocellular carcinoma was hypervascularity on hepatic
      arterial phase images with a mosaic pattern on both arterial and portal venous
      images; this finding was seen in 86% and 78% of lesions by the two observers,
      respectively. A hypervascular component was seen in 96% of lesions by both
      observers, and the observers recorded 86% and 63% of lesions as showing washout,
      respectively. Objective washout was present in 76% of lesions. Both subjective
      and objective washout correlated with an elevated alpha-fetoprotein level (p =
      0.01). CONCLUSION: The appearances of hepatocellular carcinoma on images obtained
      using MDCT scanners are similar to those described for images obtained using
      single-detector helical scanners. However, the prevalence of hypervascular
      hepatocellular carcinoma on MDCT images is higher than previously described on
      single-detector helical images and most lesions showed washout on portal venous
      MDCT images.

PMID- 14975965
TI  - Hepatic capsular retraction in metastatic carcinoma of the breast occurring with
      increase or decrease in size of subjacent metastasis.
AB  - OBJECTIVE: We evaluated the prevalence and significance of hepatic capsular
      retraction in hepatic metastases from breast cancer and correlated these with
      metastatic number, size, change in size over time, breast tumor histopathology,
      chemotherapeutic regimen, and tumor-receptor status. MATERIALS AND METHODS:
      Abdominal CT scans of 200 consecutive women with breast carcinoma (mean age, 57
      years; range, 33-81 years), obtained over a 7-month period, were retrospectively
      reviewed. Fifty-eight women had hepatic metastases. Two hundred seventy-two CT
      scans, including present and prior examinations (mean [+/- SD], 4.6 +/- 2 per
      patient), were evaluated. The number and diameter of liver metastases at all
      examinations, chemotherapeutic agents used, histopathologic diagnosis of breast
      tumor, and tumor-receptor status were compared in patients with and without
      capsular retraction. Descriptive analyses of the variables and comparisons of
      means and proportions as well as correlations were conducted. RESULTS: Hepatic
      capsular retraction was observed in 29 patients with hepatic metastases (50%).
      Retraction ranged from 1 to 10 mm in depth. Patients with capsular retraction had
      significantly larger metastases than those without retraction (p < 0.05). The
      associations between retraction and increase in size of the subjacent metastasis
      and between retraction and decrease in size were statistically significant (p <
      0.05). Capsular retraction was independent of the number of hepatic metastases,
      histopathologic diagnosis, tumor-receptor status, and chemotherapeutic regimen.
      CONCLUSION: Hepatic capsular retraction is common in patients with hepatic
      metastases from breast cancer and is associated with larger metastases and both
      increase and decrease in subjacent lesion size. It is unrelated to lesion number,
      histopathology, receptor status, or chemotherapeutic regimen.

PMID- 14975966
TI  - Radiofrequency ablation of hepatic tumors: variability of lesion size using a
      single ablation device.
AB  - OBJECTIVE: In this study, we examined the variability of lesion sizes produced by
      a single radiofrequency ablation using the same device and algorithm in patients
      with small malignant hepatic tumors. MATERIALS AND METHODS: A review of the
      clinical records of 208 patients who underwent radiofrequency ablation of
      malignant hepatic tumors during a 6-year period revealed 31 patients with small
      tumors that were treated with a single ablation. Clinical data were recorded
      using standardized work sheets. Tumor and lesion sizes after ablation were
      measured from CT scans. The influences of tumor size, tumor type, presence or
      absence of cirrhosis, and tissue temperature on the ablation size were analyzed.
      RESULTS: The size of tumor before treatment ranged from 0.8 to 4.0 cm (mean
      diameter [+/- SD] = 1.8 +/- 0.9 cm) with corresponding volumes of 0.27-30.24 mL
      (mean volume = 27.1 +/- 15.9 mL). The lesion sizes after ablation ranged from 1.7
      to 5.3 cm (mean diameter = 3.6 +/- 0.7 cm) with corresponding volumes of 2.29
      75.87 mL (mean volume = 4.9 +/- 7.1 mL). Tumor type (p > 0.25), presence or
      absence of cirrhosis (p > 0.45), and tissue temperature (p = 0.055) had no
      relationship to ablation size. Tumor size had a statistically significant
      influence on ablation lesion size (p < 0.04). Ablation of small tumors (diameter
      < or = 2.25 cm, n = 32) produced random lesion sizes whereas ablation of large
      tumors (diameter > 2.25 cm, n = 11) produced larger lesions (mean diameter = 4.0
      +/- 0.8 cm). CONCLUSION: Significant variation occurs in the lesion size produced
      using the same ablation device and algorithm. These findings must be considered
      when planning ablation strategies.

PMID- 14975967
TI  - Percutaneous treatment of biliary stones: sphincteroplasty and occlusion balloon
      for the clearance of bile duct calculi.
AB  - OBJECTIVE: Our study describes the percutaneous expulsion of bile duct calculi
      into the duodenum by dilating the papilla with a balloon catheter. SUBJECTS AND
      METHODS. Patients (n = 212; 101 men and 111 women; mean age, 73 years; range, 31
      95 years) had their calculi (single, 131; multiple, 81) percutaneously expelled
      into the duodenum in 73 patients via an indwelling T tube, and in 139 via
      transhepatic or transcystic duct route. Stone expulsion was facilitated with an
      occlusion balloon after balloon sphincteroplasty and with prior mechanical
      fragmentation in only 37 patients. After the expulsion of the calculi into the
      duodenum, drainage of the main bile duct to the exterior was maintained for 2-8
      days. RESULTS: Technical success was initially 90.4%, increasing to 93% at the
      second attempt. There were 13 failures due to the large size of the calculi in
      nine patients, excessive tortuosity of the T tube (Kher tube) in one, and
      breaches of the established protocol in two. Residual lithiasis was resolved in
      98.6% of cases, decreasing to 92% in the group of native, or nonresidual,
      lithiasis. There were 10 major complications (hemobilia) with three cases of poor
      clinical outcome: hepatic necrosis, multiorgan failure, or death. CONCLUSION:
      Percutaneous anterograde evacuation of bile duct stones with dilatation of the
      papilla using an angioplasty catheter and assisted with an occlusion balloon to
      expel the calculi is a cost-effective, nontraumatic, and safe procedure that
      retains the anatomic and functional integrity of the sphincter. It is a viable
      alternative procedure in the treatment of bile duct lithiasis.

PMID- 14975968
TI  - CT density measurements for characterization of adrenal tumors ex vivo:
      variability among three CT scanners.
AB  - OBJECTIVE: Many studies have suggested that Hounsfield measurements on unenhanced
      CT can reliably differentiate adrenal adenomas from nonadenomas using a scanner
      independent threshold level. The purpose of this study was to determine whether
      establishment of a scanner-independent threshold for differentiation of adenomas
      from nonadenomas is technically feasible. MATERIALS AND METHODS: Surgically
      resected adrenal tumor specimens (total, seven; adenomas, three; nonadenomas,
      four; size range, 17-76 mm), were placed in an anthropomorphic phantom. Lesion
      specimens were scanned with one MDCT and two single-detector scanners. Scanning
      protocols for all three scanners included variations in kilovoltage (140, 120,
      and 80 [Somatom Plus 4, Somatom VolumeZoom] or 100 [Tomoscan AV] kVp) and slice
      thickness. Hounsfield measurements were performed on exactly matched slices using
      regions of interest of a constant size. RESULTS: The difference in lesion
      Hounsfield measurements among scanning protocols with 140, 120, and 100/80 kVp
      was up to 6.2 H for the adenoma group and up to 3.8 H for the nonadenoma group.
      The comparison of the Tomoscan AV and the Somatom Plus 4 scanners showed a mean
      difference of 2.6 H at 120 kVp and of 4.6 H at 140 kVp. The differences between
      the Tomoscan AV and Somatom VolumeZoom scanners were 1.7 and 3.6 H for 120 and
      140 kVp, respectively. Between the two Somatom scanners, the divergence was 2.9
      and 3.3 H for the two kilovoltage settings. Differentiation between adenomas and
      nonadenomas was better at lower kilovoltage. Slice thickness did not affect the
      CT density measurements significantly. CONCLUSION: Significant differences in CT
      density measurements of adrenal tumors may occur when different CT scanners or
      imaging protocols are used. The dependence of measurements on scanner type and
      scanning technique makes the recommendation of a universal, scanner- and protocol
      independent threshold problematic.

PMID- 14975969
TI  - MRI of female urethral and periurethral disorders.

PMID- 14975970
TI  - Diagnosis of pelvic congestion syndrome using transabdominal and transvaginal
      sonography.
AB  - OBJECTIVE: We prospectively evaluated transabdominal and transvaginal sonographic
      findings of patients with pelvic congestion syndrome and compared them with those
      of healthy volunteers. SUBJECTS AND METHODS. We examined 32 patients with pelvic
      congestion syndrome and 35 control subjects. Using transabdominal sonography, we
      evaluated the ovarian veins for diameter and flow direction, presence of pelvic
      varicocele, diameter of the pelvic veins, change of the duplex waveform during
      the Valsalva's maneuver, volume of the uterus, and presence of polycystic changes
      in the ovaries. We compared and statistically analyzed each parameter in the
      pelvic congestion syndrome group and in the control group. RESULTS: The mean (+/-
      SD) diameter of the left ovarian vein was 0.79 +/- 0.23 cm in the pelvic
      congestion syndrome group and 0.49 +/- 0.15 cm in the control group (p = 0.000).
      Reversed caudal flow in the left ovarian vein was present in 22 of 22 patients
      and in four of 16 control subjects. Pelvic varicoceles were present in all
      patients with pelvic congestion syndrome and in six control subjects. The mean
      diameter of the left pelvic vein was 0.68 +/- 0.21 cm in the pelvic congestion
      syndrome group and 0.42 +/- 0.19 cm in the control group; the mean diameter of
      the right pelvic vein was 0.64 +/- 0.24 cm in the pelvic congestion syndrome
      group and 0.35 +/- 0.14 cm in the control group (p = 0.000). Polycystic changes
      of the ovary were present in 13 patients with pelvic congestion syndrome (40.6%)
      and four control subjects (11.4%). CONCLUSION: Sonographic findings of pelvic
      congestion syndrome were dilated left ovarian vein with reversed caudal flow,
      presence of varicocele, dilated arcuate veins crossing the uterine myometrium,
      polycystic changes of the ovary, and variable duplex waveform during the
      Valsalva's maneuver. Combined transabdominal and transvaginal sonography are
      potentially useful as a noninvasive screening tool for determining which patients
      with chronic pelvic pain may benefit from selective ovarian venography and
      transcatheter embolization.

PMID- 14975971
TI  - Complementary role of MRI after sonography in assessing bilateral urinary tract
      anomalies in the fetus.
AB  - OBJECTIVE: The objectives of our study were to evaluate the contribution of
      adding MRI findings to inconclusive sonographic data when assessing fetal urinary
      tract anomalies and to determine how this addition may affect the management of
      pregnancy. SUBJECTS AND METHODS. We prospectively used MRI to study 16 third
      trimester fetuses in whom sonography suggested bilateral urinary tract anomalies
      but failed to provide a definite diagnosis. These anomalies included enlarged
      hyperechoic kidneys (n = 6), bilateral pelvicaliceal dilatation (n = 6), renal
      cystic lesions (n = 2), and renal agenesis associated with severe oligohydramnios
      (n = 2). RESULTS: The addition of MRI to sonography modified the diagnosis in
      five fetuses. In a fetus with suspected bilateral ureteropelvic obstruction, the
      diagnosis of bilateral ureterohydronephrosis associated with reflux or
      ureterovesical junction obstruction was made. In a fetus with an enlarged bladder
      at 32 weeks' gestational age, a possible diagnosis of megacystic microcolon was
      excluded on the basis of the normal appearance of the colon. In two fetuses with
      enlarged hyperechoic kidneys, MRI showed localized medullary hyperintense lesions
      suggesting autosomal recessive polycystic kidney disease in one fetus and
      medullary cystic dysplasia in another fetus with Jeune's syndrome. In a patient
      with suspected unilateral renal agenesis, MRI showed bilateral agenesis. In four
      fetuses, the addition of MRI to sonography led to a diagnosis that modified the
      decision to continue or terminate the pregnancy. CONCLUSION: MRI can accurately
      show many urinary tract anomalies in third-trimester fetuses. It may be a useful
      complementary tool in the assessment of bilateral urinary tract anomalies of
      fetuses, particularly in cases with inconclusive sonographic findings.

PMID- 14975972
TI  - Improved interpretation of digitized mammography with wavelet processing: a
      localization response operating characteristic study.
AB  - OBJECTIVE: Our objective was the implementation and evaluation of a novel
      enhancement technique for improved interpretation of high-resolution digitized
      mammograms from computer monitors. MATERIALS AND METHODS: A wavelet algorithm was
      designed to attenuate the image spectral characteristics responsible for the long
      range image correlation that often interferes with digital display. The algorithm
      was evaluated with a localization response operating characteristic (LROC)
      experiment with 500 negative, benign, and cancer cases with masses and
      calcification clusters. Three observers reviewed the original and wavelet
      enhanced images on a 5-Mpixel monitor using a custom-made workstation user
      interface. RESULTS: Performance indexes were estimated for four different case
      combinations, each observer, and each interpretation mode. Wavelet enhancement
      improved the performance of all observers in all case combinations. Detection
      accuracy ranged from 0.678 to 0.827 for the unprocessed original data and 0.709
      0.871 for the enhanced cases. Localization accuracy ranged from 0.547 to 0.785
      for the original images and 0.568-0.847 for the enhanced cases, yielding
      increases of 5-15%. The difference between enhanced and original performances was
      statistically significant at the 0.10 level and in a few combinations at the 0.05
      level. CONCLUSION: Soft-copy digitized mammography could replace standard film
      mammography under appropriate display parameters and conditions. The optimization
      of the soft-copy quality is expected to require more advanced processing
      techniques than standard gray-scale adjustments. Wavelet-based algorithms, such
      as the one proposed here, offer better soft-copy quality than the originals and a
      better starting point for additional manual gray-scale adjustments or automated
      postprocessing.

PMID- 14975973
TI  - Computerized evaluation of mammographic lesions: what diagnostic role does the
      shape of the individual microcalcifications play compared with the geometry of
      the cluster?
AB  - OBJECTIVE: The objective of this study was to compare the diagnostic role of
      features reflecting the geometry of clusters with features reflecting the shape
      of the individual microcalcification in a mammographic computer-aided diagnosis
      system. MATERIALS AND METHODS: Three hundred twenty-four cases of clustered
      microcalcifications with biopsy-proven results were digitized at 42-microm
      resolution and analyzed on a computerized system. The shape factor and number of
      neighbors were computed for each microcalcification, and the eccentricity of the
      cluster was computed as well. The shape factor is related to the individual
      microcalcification; the average number of neighbors and the cluster eccentricity
      reflect the cluster geometry. Stepwise discriminant analysis was used to evaluate
      the contribution of the extracted features in predicting malignancy. The
      performance of a classifier based on the features selected by stepwise
      discriminant analysis was evaluated by receiver operating characteristic (ROC)
      analysis. RESULTS: To obtain the best discrimination model, we used stepwise
      discriminant analysis to select the average number of neighbors and the shape of
      the individual microcalcification, but excluded cluster eccentricity. A
      classification scheme assigned the average number of neighbors a weighting
      factor, which was 1.49 times greater than that assigned to the shape factor of
      the individual microcalcification. A scheme based only on these two features
      yielded an ROC curve with an area under the curve (A(z)) of 0.87, indicating a
      positive predictive value of 61% for 98% sensitivity. CONCLUSION: Computerized
      analysis permitted calculations reflecting the shape of individual
      microcalcification and the geometry of clusters of microcalcifications. For the
      computerized classification scheme studied, the cluster geometry was more
      effective in differentiating benign from malignant clusters than was the shape of
      individual microcalcification.

PMID- 14975974
TI  - Mammographic breast glandularity in Malaysian women: data derived from
      radiography.
AB  - OBJECTIVE: This study was undertaken to estimate mammographic breast glandularity
      in Malaysian women from radiographic data. MATERIALS AND METHODS: A mammography X
      ray unit was used to expose different thicknesses of phantom material of varying
      glandular and adipose composition at 27 kV. A least squares method was then used
      to fit the combined data of phantom glandularity, thickness, and milliampere
      seconds. The subsequent fitted equation was then applied to calculate breast
      glandularity for 705 women who underwent diagnostic mammography, who were drawn
      equally from the three major ethnic groups of Malaysia: Malay, Chinese, and
      Indian. The difference in breast glandularity among ethnic groups was tested for
      significance using the nonparametric Kruskal-Wallis test. RESULTS: The fitted
      equation gave an absolute error of less than or equal to +/- 8% when applied to
      the data from phantom exposure. The average breast glandularity of the study
      sample was 48.9% +/- 18.7%. Breast glandularity was found to decrease with breast
      thickness and age. CONCLUSION: No significant difference was seen in breast
      glandularity among the ethnic groups (p > 0.05, Kruskal-Wallis test).

PMID- 14975975
TI  - "Baby wrist": MRI of an overuse syndrome in mothers.
AB  - OBJECTIVE: The purpose of our study was to describe the MRI findings and
      interesting clinical aspects of a postpartum overuse syndrome of the wrist and
      thumb, de Quervain's tenosynovitis, or "baby wrist." CONCLUSION: Mothers may
      experience a wrist and thumb overuse syndrome, which can be diagnosed by MRI with
      an increase in size and low signal intensity on both T1- and T2-weighting, in and
      around the first dorsal tendon sheath compartment of the wrist.

PMID- 14975976
TI  - Prognostic significance of MRI findings in patients with myxoid-round cell
      liposarcoma.
AB  - OBJECTIVE: The aims of this study were to determine the prognostic significance
      of MRI findings in patients with myxoid-round cell liposarcomas and to clarify
      which MRI features best indicate tumors with adverse clinical behavior. MATERIALS
      AND METHODS: The initial MRI studies of 36 pathologically confirmed myxoid-round
      cell liposarcomas were retrospectively reviewed, and observations from this
      review were correlated with the histopathologic features. MR images were
      evaluated by two radiologists with agreement by consensus, and both univariate
      and multivariate analyses were conducted to evaluate survival with a median
      clinical follow-up of 33 months (range, 9-276 months). RESULTS: Statistically
      significant MRI findings that favored a diagnosis of intermediate- or high-grade
      tumor were large tumor size (> 10 cm), deeply situated tumor, tumor possessing
      irregular contours, absence of lobulation, absence of thin septa, presence of
      thick septa, absence of tumor capsule, high-intensity signal pattern, pronounced
      enhancement, and globular or nodular enhancement. Of these MRI findings, thin
      septa (p < 0.05), a tumor capsule (p < 0.01), and pronounced enhancement (p <
      0.01) were associated significantly, according to univariate analysis, with
      overall survival. Multivariate analysis indicated that pronounced enhancement was
      associated significantly with overall survival (p < 0.05). CONCLUSION: Contrast
      enhanced MRI findings can indicate a good or adverse prognosis in patients with
      myxoid-round cell liposarcomas.

PMID- 14975977
TI  - Lipomas, lipoma variants, and well-differentiated liposarcomas (atypical
      lipomas): results of MRI evaluations of 126 consecutive fatty masses.
AB  - OBJECTIVE: Our objectives were to evaluate the reliability of MRI in
      distinguishing simple lipomas, lipoma variants, and well-differentiated
      liposarcomas (atypical lipomas) and to identify various imaging mimics of well
      differentiated liposarcoma. MATERIALS AND METHODS: One hundred twenty-six
      consecutively imaged grossly fatty masses were retrospectively reviewed. MRI
      examinations, their prospective interpretations, and their corresponding
      pathology reports were compared to determine the reliability of MRI in
      distinguishing simple lipomas, lipoma variants, and well-differentiated
      liposarcomas. RESULTS: The success of MRI in identifying well-differentiated
      liposarcomas among other fatty masses was as follows: sensitivity, 100%;
      specificity, 83%; accuracy, 84%; positive predictive value, 38%; and negative
      predictive value, 100%. MRI was 100% specific in the diagnosis of simple lipoma.
      Sixty-three percent of lesions considered suspicious for well-differentiated
      liposarcoma were actually simple lipomas (13%) and benign lipoma variants (50%),
      including chondroid lipoma (13%), osteolipoma (6%), hibernoma (6%), lipoleiomyoma
      (6%), angiolipoma (6%), and infarcted lipoma (13%). CONCLUSION: Because of
      differences in treatment, prognosis, and long-term follow-up, it is important to
      preoperatively distinguish simple lipomas from well-differentiated liposarcomas.
      MRI is highly sensitive in the detection of well-differentiated liposarcomas and
      highly specific in the diagnosis of simple lipomas. However, when an extremity or
      body wall lesion is considered suspicious for well-differentiated liposarcoma, it
      is more likely (64%) to represent one of many benign lipoma variants.

PMID- 14975978
TI  - Cortical aneurysmal bone cyst of the tibia.

PMID- 14975979
TI  - Sonographic characteristics of peripheral nerve sheath tumors.
AB  - OBJECTIVE: We have found variability in the sonographic appearance of peripheral
      nerve sheath tumors. The purpose of this study was to characterize the
      sonographic appearances of pathologically proven peripheral nerve sheath tumors.
      CONCLUSION: Peripheral nerve sheath tumors are often hypoechoic with posterior
      acoustic enhancement and so may simulate a ganglion cyst. The presence of
      intrinsic blood flow on color Doppler sonography and peripheral nerve continuity
      suggests the diagnosis of peripheral nerve sheath tumor. Sonography cannot
      reliably distinguish neurofibromas from schwannomas.

PMID- 14975980
TI  - Unusual soft-tissue metastasis of an invasive lobular carcinoma mimicking
      fasciitis.

PMID- 14975981
TI  - Comparison of in vitro and in vivo MRI of the spine using parallel imaging.
AB  - OBJECTIVE: The purpose of this study was to compare the image quality of two
      parallel-imaging methods applied to standard turbo spin-echo T2-weighted imaging
      of the lumbar spine. MATERIALS AND METHODS: Phantom imaging and lumbar spine
      studies of 15 healthy subjects were performed using T2-weighted turbo spin-echo
      sequences obtained with and without parallel imaging (generalized autocalibrating
      partially parallel acquisition [GRAPPA] and modified sensitive encoding [mSENSE])
      on a 1.5-T magnet. The signal-to-noise ratio (SNR) and uniformity were measured
      in the phantom, and SNR and signal difference-noise ratio were evaluated in
      cerebrospinal fluid, vertebral bodies, and subcutaneous fat of the volunteers,
      using both techniques sequentially. Aliasing artifacts on GRAPPA and mSENSE
      images were visually evaluated. SNRs were compared using the Student's paired t
      test, with p values less than 0.05 considered significant. RESULTS: In the
      phantom study, when the same number of coil elements were used (n = 3), SNR and
      uniformity values obtained with standard T2-weighted turbo spin-echo sequences
      were higher than those obtained with parallel sequences. The GRAPPA SNR obtained
      with three coil elements was higher than the standard T2-weighted SNR obtained
      with one coil element. Similar findings were noted regarding uniformity. In the
      lumbar spine, GRAPPA SNR values for fat, cerebrospinal fluid, and vertebral
      bodies were significantly higher than mSENSE SNR values, with a p value less than
      0.01, but were not significantly different from T2-weighted turbo spin-echo SNR
      values. GRAPPA signal difference-noise ratio values were significantly higher
      than mSENSE signal difference-noise ratio values, with a p value less than 0.01,
      but were not significantly different from T2-weighted turbo spin-echo signal
      difference-noise ratio values. GRAPPA produced fewer aliasing artifacts than
      mSENSE. CONCLUSION: In spine MRI, GRAPPA may be used to reduce scanning time and
      yields a higher SNR than mSENSE without any increase in aliasing artifacts and
      with an SNR similar to that obtained with standard T2-weighted turbo spin-echo.

PMID- 14975982
TI  - High-resolution CT using MDCT: comparison of degree of motion artifact between
      volumetric and axial methods.
AB  - OBJECTIVE: The purpose of this study was to compare the degree of motion artifact
      on high-resolution CT images obtained using volumetric and axial (nonvolumetric)
      CT methods. CONCLUSION: Volumetric high-resolution CT is associated with
      significantly greater motion artifact compared with axial noncontiguous high
      resolution imaging.

PMID- 14975983
TI  - Thoracic CT findings of adult T-cell leukemia or lymphoma.
AB  - OBJECTIVE: The aim of this study was to assess pulmonary CT findings in patients
      with adult T-cell leukemia or lymphoma. MATERIALS AND METHODS: We retrospectively
      reviewed CT scans of the lung in 87 patients with adult T-cell leukemia or
      lymphoma who had undergone chest CT between January 1996 and March 2002 at two
      institutions. The CT scans were interpreted by two chest radiologists working in
      consensus. Parenchymal abnormalities (ground-glass attenuation, consolidation,
      nodules, thickening of bronchovascular bundles, interlobular septal thickening,
      honeycombing, crazy-paving appearance, and bronchiectasis) were evaluated, as
      were enlarged lymph nodes, pleural effusion, and pleural thickening. In 46
      patients who underwent surgical biopsy or autopsy, CT-pathologic correlation was
      performed with the actual specimens by a pathologist and two chest radiologists.
      RESULTS: On the CT scans, abnormal findings were seen in 60 patients (69.0%). CT
      findings consisted of ground-glass attenuation (n = 37), centrilobular nodules (n
      = 25), thickening of bronchovascular bundles (n = 22), and consolidation (n =
      13). These abnormalities were predominantly seen in the peripheral lung
      parenchyma (n = 26). Pathologically, these findings corresponded with atypical
      lymphocyte infiltration along the interstitium and the alveolar spaces. Pleural
      effusion and enlarged lymph nodes were found in 22 and 27 patients, respectively.
      CONCLUSION: CT findings in patients with adult T-cell leukemia or lymphoma
      consisted mainly of ground-glass attenuation, centrilobular nodules, and
      thickening of the bronchovascular bundles in the peripheral lung. These findings,
      although nonspecific, are considered suggestive of thoracic involvement in
      patients with adult T-cell leukemia or lymphoma.

PMID- 14975984
TI  - Imaging spectrum of Castleman's disease.

PMID- 14975985
TI  - MDCT evaluation of thoracic aortic anomalies in pediatric patients and young
      adults: comparison of axial, multiplanar, and 3D images.
AB  - OBJECTIVE: The objective of our study was to compare accuracies of axial,
      multiplanar, and 3D volume-rendered images in the diagnosis of thoracic aortic
      anomalies in pediatric patients and young adults. MATERIALS AND METHODS: Fourteen
      patients, 17 days to 20 years old, with thoracic aortic anomalies underwent MDCT
      using axial, multiplanar, and 3D volume-rendering imaging. All images were
      reviewed by three radiologists for position of the aortic arch, coarctation,
      vascular compression of the airway, collateral vessel formation, and
      aortopulmonary shunts (patent ductus arteriosus). Final diagnosis was determined
      by echocardiography, conventional angiography, bronchoscopy, or surgery.
      Diagnostic accuracy, sensitivity, and interobserver agreement were evaluated.
      RESULTS: Average accuracies (average of the three observers for a correct
      diagnosis) were greater than or equal to 96% for diagnoses of aortic position and
      airway narrowing on all image types. For the diagnosis of coarctation, average
      sensitivities (average of the three observers for a true diagnosis) were 73% for
      axial, 100% for multiplanar, and 100% for 3D volume-rendered images. For the
      diagnosis of patent ductus arteriosus, average sensitivities were 78% for axial,
      94% for multiplanar, and 89% for 3D volume-rendered images. No patients in this
      study had collateral vessel formation. For the diagnosis of absence of collateral
      vessel formation, average sensitivities were 100% for axial, 100% for
      multiplanar, and 100% for 3D volume-rendered images. There were no significant
      statistical differences in diagnostic performances, agreement with truth, or
      confidence scores among observers or imaging formats (p > 0.05). CONCLUSION:
      Axial, multiplanar, and 3D volume-rendered images serve equally well as methods
      for assessing the side of the aorta to diagnose anomalies. For evaluation of
      coarctation and patent ductus arteriosus, multiplanar and 3D volume-rendered
      images perform slightly better than axial images.

PMID- 14975986
TI  - Infantile hepatic hemangiomas: clinical and imaging findings and their
      correlation with therapy.
AB  - OBJECTIVE: This study was undertaken to determine different imaging patterns in
      infantile hepatic hemangiomas and to explore the relationship between clinical
      presentations, imaging findings, and response to therapy. MATERIALS AND METHODS:
      The imaging studies and clinical records of all patients with infantile hepatic
      hemangiomas from two tertiary children's hospitals were reviewed. Univariate and
      multivariate stepwise logistic regression techniques were used to determine
      whether clinical presentation and imaging variables differentiated the type of
      treatment required. RESULTS: Typical hemangiomas appeared as focal or multifocal
      T2-hyperintense spheres with centripetal contrast enhancement and dilated feeding
      and draining vessels. Three atypical patterns included focal mass lesions with
      central varix with or without direct shunts, focal mass with central necrosis or
      thrombosis, and massive hemangiomatous involvement of the liver with abdominal
      vascular compression. In general, patients with focal lesions without high flow
      needed no treatment, and those with central varix and direct shunts developed
      severe high-output cardiac failure that responded quickly to embolization. The
      pattern of massive replacement of liver was associated with hypothyroidism,
      abdominal compartment syndrome, and a high mortality rate. Multivariate analysis
      of 55 patients indicated that congestive heart failure was the only independent
      predictor of treatment (p = 0.005). The presence of a shunt was the only
      independent factor associated with embolization or surgery (p = 0.002).
      CONCLUSION: Although the imaging features of infantile hepatic hemangiomas vary
      to some extent, MRI features are typical in most patients and certain imaging
      findings are predictive of the clinical course. MRI is the technique of choice in
      diagnosing infantile hepatic masses.

PMID- 14975987
TI  - Creating an international comprehensive web-based curriculum in pediatric
      radiology.
AB  - OBJECTIVE: This article describes the creation of a standardized comprehensive
      resident curriculum in pediatric radiology that uses adult learning principles
      authored by international experts and addresses the six general competencies
      required by the Accreditation Council for Graduate Medical Education. CONCLUSION:
      Web-based learning with an online curriculum has the potential to become an
      integral component of residency training. The use of radiology experts as authors
      allows compilation of an authoritative, comprehensive, and current body of
      knowledge that enhances the current teaching file approach to Web-based
      instruction in radiology. We describe the approach, design, and tools necessary
      for the construction of a complete Web-based curriculum in pediatric radiology
      that includes self-assessment through pre- and post-testing, text with
      interactive images, curriculum evaluation, and the ability to record trainee
      demographics.

PMID- 14975988
TI  - Pharyngeal perforation from an impacted fish.

PMID- 14975989
TI  - Correlating MRI and histologic tumor thickness in the assessment of oral tongue
      cancer.
AB  - OBJECTIVE: Tumor thickness in oral tongue cancer is an important independent
      prognostic factor for local recurrence, nodal metastasis, and patient survival.
      An accurate preoperative assessment of tumor thickness is therefore essential for
      optimal treatment planning. The aim of our study was to evaluate the accuracy of
      MRI findings for the preoperative measurement of tumor thickness. SUBJECTS AND
      METHODS. Eighteen patients with oral tongue cancer underwent preoperative MRI of
      the tongue. After surgery, the glossectomy specimens were serially sectioned. The
      radiologic tumor thickness of contrast-enhanced T1-weighted and T2-weighted
      images was compared with the histologic tumor thickness using our proposed tumor
      thickness staging classifications. These included stage I (tumor < or = 3 mm),
      stage II (> 3 mm but < or = 9 mm) and stage III (> 9 mm). RESULTS: The overall
      accuracy in assessment of proposed tumor thickness staging using contrast
      enhanced T1-weighted and T2-weighted images was 83% and 56%, respectively. The
      radiologic tumor thickness as measured on contrast-enhanced T1-weighted and T2
      weighted images had significant correlation with histologic tumor thickness (R =
      0.938 and 0.941, respectively). CONCLUSION: MR images provide satisfactory
      accuracy for the measurement of tumor thickness and staging of oral tongue
      cancer. Preoperative MRI is recommended to assist in treatment planning for
      patients with this disease.

PMID- 14975990
TI  - Osmotic demyelination syndrome in end-stage renal disease after recent
      hemodialysis: MRI of the brain.
AB  - OBJECTIVE: Osmotic demyelination syndrome has been reported in patients with end
      stage renal disease, but the specific MRI findings in this patient group have not
      been documented in detail. Our aims were to present the brain MRI findings during
      an episode after hemodialysis and at follow-up, and to identify possible factors
      that may contribute to lesion development. MATERIALS AND METHODS: Seventeen
      patients with osmotic demyelination syndrome who had undergone hemodialysis at
      least once and had brain MRI examinations were retrospectively reviewed.
      Neurologic and MRI examinations were performed during a clinical episode. Serum
      levels of sodium, creatinine, blood urea nitrogen, and glucose were assessed, and
      serum osmolality and the ratio of blood urea nitrogen to creatinine (BUN:Cr) were
      calculated. Follow-up MRI was performed in nine cases. Laboratory and imaging
      findings were evaluated. RESULTS: An altered level of consciousness and
      convulsions were the most common neurologic symptoms. The pons was involved in 11
      patients (65%) and extrapontine sites in 12 (71%). Four patients had
      dysequilibrium syndrome. Follow-up MRI showed complete resolution in six patients
      and lesion reduction in three within a short time. The most common biochemical
      changes at the time of MRI were hyponatremia and low BUN:Cr in the blood. Only
      one patient showed rapid correction of hyponatremia and a rapid change in
      osmolality during the acute stage. CONCLUSION: In patients who develop osmotic
      demyelination syndrome after hemodialysis, the lesions may involve the pons or
      the pons and extrapontine sites. Most lesions that were followed up resolved
      rapidly and almost completely, favoring transient edema rather than
      demyelination. Blood chemistries suggested underlying changes in osmolality,
      particularly as a result of urea shift from the extracellular fluid.

PMID- 14975991
TI  - Direct communication of radiologic abnormalities: pushing the pendulum back.

PMID- 14975992
TI  - Gas in the epidural space after percutaneous vertebroplasty: where does the gas
      come from?

PMID- 14975993
TI  - Pregnancy policy.

PMID- 14975994
TI  - Fitz-Hugh-Curtis syndrome caused by Chlamydia trachomatis: atypical CT findings.

PMID- 14975995
TI  - Why CT-guided?

PMID- 14975996
TI  - Cavernous sinus syndrome.

PMID- 14975997
TI  - Today's plantiff's attorneys.

PMID- 14975998
TI  - CT findings in patient with head injury from captive bolt gun.

PMID- 14975999
TI  - Lumbar subarachnoid air after head trauma.

PMID- 14976000
TI  - MR enteroclysis in solitary ileal metastasis from renal cell carcinoma.

PMID- 14976001
TI  - Pulmonary and lower extremity vascular lesions in a patient with homocystinuria:
      radiologic findings.

PMID- 14976002
TI  - Is oxidative stress the pathogenic mechanism underlying insulin resistance,
      diabetes, and cardiovascular disease? The common soil hypothesis revisited.
AB  - Type 2 diabetes is a worldwide increasing disease resulting from the interaction
      between a subject's genetic makeup and lifestyle. In genetically predisposed
      subjects, the combination of excess caloric intake and reduced physical activity
      induces a state of insulin resistance. When beta cells are no longer able to
      compensate for insulin resistance by adequately increasing insulin production,
      impaired glucose tolerance appears, characterized by excessive postprandial
      hyperglycemia. Impaired glucose tolerance may evolve into overt diabetes. These 3
      conditions, ie, insulin resistance, impaired glucose tolerance, and overt
      diabetes, are associated with an increased risk of cardiovascular disease.
      Because all these conditions are also accompanied by the presence of an oxidative
      stress, this article proposes oxidative stress as the pathogenic mechanism
      linking insulin resistance with dysfunction of both beta cells and endothelium,
      eventually leading to overt diabetes and cardiovascular disease. This hypothesis,
      moreover, may also contribute to explaining why treating cardiovascular risk with
      drugs, such as calcium channel blockers, ACE inhibitors, AT-1 receptor
      antagonists, and statins, all compounds showing intracellular preventive
      antioxidant activity, results in the onset of new cases of diabetes possibly
      being reduced.

PMID- 14976003
TI  - CD154/CD40-mediated expression of CD154 in endothelial cells: consequences for
      endothelial cell-monocyte interaction.
AB  - OBJECTIVE: CD40 ligand (CD154) expressed on activated T helper cells is a key
      costimulatory molecule for antigen-presenting cells expressing the corresponding
      receptor CD40. Moreover, CD40 stimulation in nonimmune cells, such as endothelial
      cells, may play an important role in atherogenesis. One gene product that is
      induced in endothelial cells on exposure to CD154 is CD154 itself. METHODS AND
      RESULTS: In human primary cultured endothelial cells, constitutive CD154
      expression was virtually absent and insensitive to proinflammatory cytokines such
      as tumor necrosis factor alpha and/or interferon-gamma. However, CD154 expression
      was markedly induced, both on the mRNA and protein level, after CD40 stimulation.
      Moreover, CD40-positive human monocytes (THP-1 cell line) transmigrating through
      CD154-expressing endothelial cells responded with an increased expression of
      interleukin-1beta (IL-1beta) mRNA, indicative of their activation. This increase
      in IL-1beta expression was confirmed on the protein level and could be abrogated
      by prior treatment of the endothelial cells with a neutralizing anti-CD154
      antibody. CONCLUSIONS: By way of CD154-induced CD154 expression, human
      endothelial cells thus seem capable of influencing the progression of
      proinflammatory reactions, including atherogenesis through activation of
      extravasating monocytes.

PMID- 14976004
TI  - Signaling in leukocyte transendothelial migration.
AB  - Under a variety of (patho) physiological conditions, leukocytes will leave the
      bloodstream by crossing the endothelial monolayer that lines the vessels and
      migrate into the underlying tissues. It is now clear that the process of
      extravasation involves a range of adhesion molecules on both leukocytes and
      endothelial cells, as well as extensive intracellular signaling that drives
      adhesion and chemotaxis on the one hand and controls a transient modulation of
      endothelial integrity on the other. We review here the current knowledge of the
      intracellular signaling pathways that are activated in the context of
      transendothelial migration in leukocytes and in endothelial cells. In leukocytes,
      polarization of receptors and of the signaling machinery is of key importance to
      drive adhesion and directional migration. Subsequent adhesion-induced signaling
      in endothelial cells, mediated by Rho-like GTPases and reactive oxygen species,
      induces a transient and focal loss of endothelial cell-cell adhesion to allow
      transmigration of the leukocyte. This review underscores the notion that we have
      likely just scratched the surface in revealing the complexity of the signaling
      that controls leukocyte transendothelial migration.

PMID- 14976005
TI  - Molecular Electronics III. Proceedings of the 6th United Engineering Foundation
      Conference on Molecular Electronics, Science and Technology. December 15-19,
      2002, Key West, Florida, USA.

PMID- 14976006
TI  - An overview of the first half-century of molecular electronics.
AB  - The seminal ideas from which molecular electronics has developed were the
      theories of molecular conduction advanced in the late 1940s by Robert S. Mulliken
      and Albert Szent-Gyorgi. These were, respectively, the concept of donor-acceptor
      charge transfer complexes and the possibility that proteins might in fact not be
      insulators The next two decades saw a burgeoning of experimental and theoretical
      work on electron transfer systems, together with a lone effort by D.D. Eley on
      conduction in proteins. The call by Feynman in his famous 1959 lecture There's
      Plenty of Room at the Bottom for chemists, engineers and physicists to combine to
      build up structures from the molecular level was influential in turning attention
      to the possibility of engineering single molecules to function as elements in
      information-processing systems. This was made tangible by the proposal of Aviram
      and Ratner in 1974 to use a Mulliken-like electron donor-acceptor molecule as a
      molecular diode, generalizing molecular conduction into molecular electronics. In
      the early 1970s the remarkably visionary work of Forrest L. Carter of the U.S.
      Naval Research Laboratories began to appear: designs for molecular wires,
      switches, complex molecular logic elements, and a host of related ideas were
      advanced. Shortly after that, conferences on molecular electronics began to be
      held, and the interdisciplinary programs that Feynman envisaged. There was a
      surge in both experimental and theoretical work in molecular electronics, and the
      establishment of many research centres. The past five years or so have seen
      extraordinarily rapid progress in fabrication and theoretical understanding. The
      history of how separate lines of research emanating from fundamental insights of
      about 50 years ago have coalesced into a thriving international research program
      in what might be called the ultimate nanotechnology is the subject of this
      review; it concentrates on the lesser-appreciated early developments in the
      field.

PMID- 14976007
TI  - Mechanism of electron conduction in self-assembled alkanethiol monolayer devices.
AB  - Electron tunneling through self-assembled monolayers (SAMs) of alkanethiols was
      investigated using nanometer scale devices that allow temperature-dependent
      current-voltage, I(V, T), measurements. The I(V, T) measurement results show, for
      the first time, temperature-independent electron transport characteristics,
      proving direct tunneling as the transport mechanism in alkanethiol SAMs. The
      measured tunneling currents can be fitted with theoretical calculations using the
      modified rectangular barrier model of direct tunneling with a barrier height
      Phi(B) = 1.42 +/- 0.04 eV and a non-ideal barrier factor alpha = 0.65 +/- 0.01
      (that may correspond to effective mass of 0.42 m). From the length-dependent
      conduction measurement on different alkanethiols of various lengths, the
      tunneling current exhibits exponential dependence on the molecular length, d, as
      I proportional, variant exp(-betad), where beta is a decay coefficient that was
      found to be bias-dependent and agrees with the existing theory of direct
      tunneling. A zero field decay coefficient beta(0) of 0.79 +/- 0.01 A(-1) was
      obtained.

PMID- 14976008
TI  - Electrical characterization of metal-molecule-silicon junctions.
AB  - Direct assembly of molecules onto silicon surfaces is of particular interest for
      potential employment in hybrid organic-semiconductor devices. In the study we
      report here, aryl diazonium salts were used to assemble covalently bound
      molecular groups on a hydride-passivated, oxide-free n-type Si(111) surface. The
      reaction of 4-(trimethylsilylethynyl)benzenediazonium tetrafluoroborate generates
      a molecular layer of 4-(trimethylsilylethynyl)phenylene (TMS-EP) on the n++
      Si(111) surface. The monolayer modifies the electrical properties of the
      interface and exhibits nonlinear current-voltage characteristics, as compared
      with the ohmic behavior observed from metal-n++-Si(111) junctions. The result of
      current-voltage measurements at variable temperatures (from 300 to 10 K) on
      samples made with the TMS-EP molecule does not show significant thermally
      activated transport, indicating that tunneling is the dominant transport
      mechanism. The measured data is compared to a tunneling model.

PMID- 14976009
TI  - NEGF-HF method in molecular junction property calculations.
AB  - Electron-electron interaction is an essential issue in predicting the properties
      of a molecular conduction junction. An accurate treatment requires taking proper
      account of the potential distribution across the junction as well as for the
      change in electronic structure under the external voltage drop. Another important
      point is the necessity to treat molecules as open quantum systems. In this paper
      we address these issues within the framework of the non-equilibrium Green's
      function formalism at the Hartree-Fock level (NEGF-HF), which permits a self
      consistent treatment of the problem. We apply the method to study the
      experimentally observed asymmetry in the I-V curves with respect to polarity of
      voltage bias in Hg-Au junctions containing bilayers of alkanethiols of various
      chain lengths. The origin of the effect is suggested to be the asymmetric
      behavior of the character of the highest occupied molecular orbital (HOMO) of the
      junction at opposite biases, which leads to different effective barriers for
      electron transfer across the junction at opposite signs of the voltage drop. The
      calculated potential profile shows the capacitor-like nature for the junction
      with the weak link.

PMID- 14976011
TI  - Molecular landers as probes for molecular device-metal surface interactions.
AB  - Specifically designed series of molecules (landers), comprising a central rigid
      polyaromatic core and several spacers that decouple the board from the metallic
      surface, have been synthesized. UHV-STM studies, on one hand, have shown
      important distortions of the molecule by interaction with the substrate. On the
      other hand, surface restructuring results from the presence of the molecules.

PMID- 14976010
TI  - A simple theoretical model to study the voltage dependence of the electronic
      structure of phenyl ethylene oligomers.
AB  - Although very few measurements have appeared in the open literature and there
      seems to be a controversy about the existence of the NDR phenomenon in molecules,
      the prospects of building such systems have attracted significant attention. In
      the work reported in this paper we used a model based on DFT calculations of the
      electronic structure of the 2'-amino-4,4'-di(ethynylphenyl)-5'-nitro-1
      benzenethiolate molecule (previously reported to exhibit NDR behavior) in a
      capacitor-like electric field that mimics the potential spatial profile of the
      junction. Our results suggest that in these systems, there seems to be a
      correlation between a substantial charge density rearrangement of the neutral
      bridge at a threshold voltage and the NDR behavior observed in previous
      experiments. Our results highlight the importance of inclusion of the field in
      the study of electrified interfaces. We applied this model to a fluorine
      substituted conjugated diethynylphenyl molecule and found that these calculations
      predict similar behavior. Results based on extended system calculations,
      including electrode-molecule interactions, confirm the validity of the model
      based on the isolated molecule and suggest the use of these simple models to
      rationally design molecular devices with similar switching characteristics.

PMID- 14976012
TI  - Optical switching in chiropticenes.
AB  - Chiropticenes are a novel class of predesigned chiral molecular switches that are
      triggered and controlled by a combination of both light and electric field.
      Chiropticenes contain an optically active (chiral) center and, as a consequence,
      provide two accessible equal energy bistable states resembling the molecular
      elements of binary logic. Structural engineering of the basic switch design is
      investigated to modulate the thermal and optical switching behavior of the
      resulting compounds. A simple screening methodology is presented to detect
      switching behavior in the solid state employing standard NMR and FT-IR
      spectroscopy. Validation of this method is demonstrated by the switching
      properties of newly synthesized anthraquinone dye based Chiropticenes.
      Functioning as a chiroptical dipole switch, Chiropticenes promise broad
      applications in emerging optoelectronic and molecular electronic technologies.

PMID- 14976013
TI  - Synthesis, electronic properties, and applications of indium oxide nanowires.
AB  - Single-crystalline indium oxide nanowires were synthesized using a laser ablation
      method and characterized using various techniques. Precise control over the
      nanowire diameter down to 10 nm was achieved by using monodisperse gold clusters
      as the catalytic nanoparticles. In addition, field effect transistors with on/off
      ratios as high as 10(4) were fabricated based on these nanowires. Detailed
      electronic measurements confirmed that our nanowires were n-type semiconductors
      with thermal emission as the dominating transport mechanism, as revealed by
      temperature-dependent measurements. Furthermore, we studied the chemical sensing
      properties of our In(2)O(3) nanowire transistors at room temperature. Upon
      exposure to a small amount of NO(2) or NH(3), the nanowire transistors showed a
      decrease in conductance of up to five or six orders of magnitude, in addition to
      substantial shifts in the threshold gate voltage. Our devices exhibit
      significantly improved chemical sensing performance compared to existing solid
      state sensors in many aspects, such as the sensitivity, the selectivity, the
      response time and the lowest detectable concentrations. We have also demonstrated
      the use of UV light as a "gas cleanser" for In(2)O(3) nanowire chemical sensors,
      leading to a recovery time as short as 80 seconds.

PMID- 14976014
TI  - Electrical transport study of phenylene-based pi-conjugated molecules in a three
      terminal geometry.
AB  - We fabricated three-terminal devices with conjugated molecules. Two different
      device layouts were used to measure both very short molecules (with one or two
      benzene rings) and relatively long ones (as long as 8 nm). To achieve an optimum
      gate effect, we used aluminum gates covered with a very thin native oxide layer.
      Molecules with thiol end groups were positioned between the source and drain
      electrodes by self-assembly. The device yield was low for short molecules, most
      likely due to defects in the self-assembled monolayers. Most of the devices made
      with short molecules did not show any gate effect at all; a small gate effect was
      only observed in two samples made with 1,3-benzenedithiol. Some devices showed
      clear negative differential conductance peaks. In some devices made with long
      molecules, we observed a small change of conductance with gate voltage.

PMID- 14976015
TI  - Analysis of electron transfer in substituted biphenylmethane.
AB  - We present an analysis of electron transfer in a molecular structure containing
      two phenyl rings connected by a methylene barrier, with the addition of a donor
      group (NH(2)) on one ring and an acceptor group (NO(2)) on the other. Such
      molecules are among those currently being considered for the implementation of
      molecular circuits for information processing. We have performed both a study of
      the response of electron polarization to the application of an external
      electrostatic perturbation, and an analysis of the time-dependent behavior of
      electron transfer across the barrier. A detailed evaluation of the electron
      affinity and of the ionization energy of the molecular structure under
      investigation has also been performed, obtaining results that show the inadequacy
      of representations in terms of simple HOMO and LUMO orbitals.

PMID- 14976016
TI  - CrossNets: high-performance neuromorphic architectures for CMOL circuits.
AB  - The exponential, Moore's Law, progress of electronics may be continued beyond the
      10-nm frontier if the currently dominant CMOS technology is replaced by hybrid
      CMOL circuits combining a silicon MOSFET stack and a few layers of parallel
      nanowires connected by self-assembled molecular electronic devices. Such hybrids
      promise unparalleled performance for advanced information processing, but require
      special architectures to compensate for specific features of the molecular
      devices, including low voltage gain and possible high fraction of faulty
      components. Neuromorphic networks with their defect tolerance seem the most
      natural way to address these problems. Such circuits may be trained to perform
      advanced information processing including (at least) effective pattern
      recognition and classification. We are developing a family of distributed
      crossbar network (CrossNet) architectures that permit the combination of high
      connectivity neuromorphic circuits with high component density. Preliminary
      estimates show that this approach may eventually allow us to place a cortex-scale
      circuit with about 10(10) neurons and about 10(14) synapses on an approximately
      10 x 10 cm(2) silicon wafer. Such systems may provide an average cell-to-cell
      latency of about 20 nsec and, thus, perform information processing and system
      training (possibly including self-evolution after initial training) at a speed
      that is approximately six orders of magnitude higher than in its biological
      prototype and at acceptable power dissipation.

PMID- 14976017
TI  - Conductive probe AFM measurements of conjugated molecular wires.
AB  - The electrical conduction of self-assembled monolayers (SAMs) made from
      conjugated molecules was measured using conductive probe atomic force microscopy
      (CP-AFM), with a focus on the molecular structural effect on conduction. First,
      the electrical conduction of SAMs made from phenylene oligomer SAMs was measured.
      The resistances through the monolayers increased exponentially with an increase
      in molecular length and the decay constants of transconductance beta were about
      0.45 to 0.61 A(-1) measured at lower bias region. We further investigated the
      influence of applied load on the resistances. The resistances through terphenyl
      SAMs increased with an increase in the applied load up to 14 nN. Second, using an
      insertion technique into insulating alkanethiol SAMs, the electrical conduction
      of single conjugated terphenyl methanethiol and oligo(para-phenylenevinylene)
      (OPV) molecules embedded into insulating alkanethiol SAMs were measured.
      Electrical currents through these single molecules of OPVs were estimated to be
      larger than those through single terphenyl molecules, suggesting that the OPV
      structure can increase the electrical conduction of single molecules. Third,
      apparent negative differential resistance (NDR) was observed at higher bias
      measurements of SAMs. The appearance of NDR might be related to roughness of SAM
      surface, because apparent NDR was often observed on rough surfaces. In any case,
      the tip-molecule contact condition strongly affected carrier transport through
      metal tip/SAM/metal junction.

PMID- 14976019
TI  - Single-molecule designs for electric switches and rectifiers.
AB  - A design for molecular rectifiers is proposed. Current rectification is based on
      the spatial asymmetry of a molecule and requires only one resonant conducting
      molecular orbital. Rectification is caused by asymmetric coupling of the orbital
      to the electrodes, which results in asymmetric movement of the two Fermi levels
      with respect to the orbital under external bias. Results from numerical studies
      of the family of suggested molecular rectifiers, HS-(CH(2))(n)
      C(6)H(4)(CH(2))(m)SH, are presented. Current rectification ratios in excess of
      100 are achievable for n = 2 and m > 6. A class of bistable stator-rotor
      molecules is proposed. The stationary part connects the two electrodes and
      facilitates electron transport between them. The rotary part, which has a large
      dipole moment, is attached to an atom of the stator via a single sigma bond.
      Electrostatic bonds formed between the oxygen atom of the rotor and hydrogen
      atoms of the stator make the symmetric orientation of the dipole unstable. The
      rotor has two potential minima with equal energy for rotation about the sigma
      bond. The dipole can be flipped between the two states by an external electric
      field. Both rotor-orientation states have asymmetric current-voltage
      characteristics that are the reverse of each other, so they are distinguishable
      electrically. Theoretical results on conformation, energy barriers, retention
      times, switching voltages, and current-voltage characteristics are presented for
      a particular stator-rotor molecule. Such molecules could be the base for single
      molecule switches, reversible diodes, and other molecular electronic devices.

PMID- 14976018
TI  - A protein-based three terminal electronic device.
AB  - Because of their natural functional characteristics, involving inter- and
      intramolecular electron transfer, metalloproteins are good candidates for
      biomolecular nanoelectronics. In particular, blue copper proteins, such as
      azurin, can bind gold via a disulfide site present on its surface and they have a
      natural electron transfer activity that can be exploited for the realization of
      molecular switches whose conduction state can be controlled by tuning their redox
      state through an external voltage source. We report on the implementation of a
      prototype of protein transistor operating in air and in the solid state, based on
      this class of proteins. The three terminal devices exhibit various functions
      depending on the relative source-drain and gate-drain voltages bias, opening a
      way to the implementation of a new generation of logic architectures.

PMID- 14976020
TI  - TranSIESTA: a spice for molecular electronics.
AB  - Our recently developed method, TranSIESTA, enables modelling of molecular
      electronic devices under operation conditions. The method is based on density
      functional theory, and calculates the self-consistent electronic structure of a
      nanostructure coupled to three-dimensional electrodes with different
      electrochemical potentials. It uses a full atomistic ab initio description of
      both the electrodes and the nanoscale device. The calculations reveal information
      about the scattering states, transmission coefficients, electron current, and non
      equilibrium forces in the systems. In this paper we use the method to investigate
      the electrical properties of three ring phenyl-ethynylene oligomers (OPE). We
      present results for the electrical effect of side groups and molecular
      conformations of the molecules. The calculations indicate that molecular
      switching and negative differential conductance (NDC) are related to rotations of
      the middle phenyl ring.

PMID- 14976021
TI  - Molecular electronics on silicon: an ultrahigh vacuum scanning tunneling
      microscopy study.
AB  - An ultrahigh vacuum scanning tunneling microscope (STM) was employed as a tool to
      characterize two distinct molecular electronic strategies on the Si(100) surface.
      Initially, the self-directed growth of one-dimensional styrene molecular chains
      on hydrogen-passivated Si(100) was investigated. High-resolution empty states
      imaging of these styrene nanostructures confirms alignment of phenyl groups along
      the chain. However, attempts at STM charge transport measurements were limited by
      tip induced desorption of styrene molecules. Consequently, an alternative oxygen
      radical chemistry was also investigated. In particular, the chemical adsorption
      of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) onto clean Si(100) leads to the
      formation of an exceptionally stable silicon-oxygen bond that can withstand high
      bias charge transport measurements up to +/- 5 volts. Direct charge transport
      measurements through individual TEMPO molecules on degenerately n-type doped
      Si(100) reveal room temperature negative differential resistance behavior for
      negative sample biases exceeding - 3 volts.

PMID- 14976022
TI  - The appropriateness of density-functional theory for the calculation of molecular
      electronics properties.
AB  - As molecular electronics advances, efficient and reliable computation procedures
      are required for the simulation of the atomic structures of actual devices, as
      well as for the prediction of their electronic properties. Density-functional
      theory (DFT) has had widespread success throughout chemistry and solid-state
      physics, and it offers the possibility of fulfilling these roles. In its modern
      form it is an empirically parameterized approach that cannot be extended toward
      exact solutions in a prescribed way, ab initio. Thus, it is essential that the
      weaknesses of the method be identified and likely shortcomings anticipated in
      advance. We consider four known systematic failures of modern DFT: dispersion,
      charge transfer, extended pi conjugation, and bond cleavage. Their ramifications
      for molecular electronics applications are outlined and we suggest that great
      care is required when using modern DFT to partition charge flow across electrode
      molecule junctions, screen applied electric fields, position molecular orbitals
      with respect to electrode Fermi energies, and in evaluating the distance
      dependence of through-molecule conductivity. The causes of these difficulties are
      traced to errors inherent in the types of density functionals in common use,
      associated with their inability to treat very long-range electron correlation
      effects. Heuristic enhancements of modern DFT designed to eliminate individual
      problems are outlined, as are three new schemes that each represent significant
      departures from modern DFT implementations designed to provide a priori
      improvements in at least one and possible all problem areas. Finally, fully
      semiempirical schemes based on both Hartree-Fock and Kohn-Sham theory are
      described that, in the short term, offer the means to avoid the inherent problems
      of modern DFT and, in the long term, offer competitive accuracy at dramatically
      reduced computational costs.

PMID- 14976023
TI  - Unimolecular rectifiers and proposed unimolecular amplifier.
AB  - The rectification by three molecules that form Langmuir-Blodgett monolayers
      between gold electrodes is reviewed, along with a proposal for the means to
      obtain gain in a unimolecular amplifier, the molecular analog of a bipolar
      junction transistor.

PMID- 14976024
TI  - Understanding charge transport in molecular electronics.
AB  - For molecular electronics to become a viable technology the factors that control
      charge transport across a metal-molecule-metal junction need to be elucidated. We
      use an experimentally simple crossed-wire tunnel junction to interrogate how
      factors such as metal-molecule coupling, molecular structure, and the choice of
      metal electrode influence the current-voltage characteristics of a molecular
      junction.

PMID- 14976025
TI  - Molecular assembly and self-assembly: molecular nanoscience for future
      technologies.
AB  - In this review the emerging science of single molecules is discussed in the
      perspective of nanoscale molecular functions and devices. New methods for the
      controlled assembly of well-defined molecular nanostructures are presented: self
      assembly and single molecular positioning. The observation and selective
      modification of conformation, electronics, and molecular mechanics of individual
      molecules and molecular assemblies by scanning probes is demonstrated. To
      complement this scientific review, some of the possible consequences and visions
      for future developments are discussed, as far as they derive from the presented
      systems. The prospects of nanoscale science to stimulate technological evolution
      are exemplified.

PMID- 14976026
TI  - A three terminal ring interferometer logic gate.
AB  - We propose a carbon-based logic gate where and, or, and xor logic operations are
      available. It consists of a carbon nanotube (CNT) ring coupled to three external
      CNT-leads, two of them used as input channels, and the third as the output
      channel. The total transmission for two inputs displays characteristic
      interference effects. The constructive interference leads to total transmission
      significantly larger than that for a single input and validates and gates,
      whereas the destructive interference corresponds to xor gates. For or gates a
      negligible interference between the transmittance of each single inputs is
      needed.

PMID- 14976027
TI  - Scalability simulations for nanomemory systems integrated on the molecular scale.
AB  - Simulations were performed to assess the prospective performance of a 16 Kbit
      nanowire-based electronic nanomemory system. Commercial off-the-shelf
      microcomputer system modeling software was applied to evaluate the operation of
      an ultra-dense storage array. This array consists of demonstrated experimental
      non-volatile nanowire diode switches, plus encoder-decoder structures consisting
      of demonstrated experimental nanowire-based nanotransistors, with nanowire
      interconnects among all the switching devices. The results of these simulations
      suggest that a nanomemory of this type can be operated successfully at a density
      of 10(11) bits/cm(2). Furthermore, modest device alterations and system design
      alternatives are suggested that might improve the performance and the scalability
      of the nanomemory array. These simulations represent early steps toward the
      development of a simulation-based methodology to guide nanoelectronic system
      design in a manner analogous to the way such methodologies are used to guide
      microelectronic system design in the silicon industry.

PMID- 14976028
TI  - Analysing microarray data using modular regulation analysis.
AB  - MOTIVATION: Microarray experiments measure complex changes in the abundance of
      many mRNAs under different conditions. Current analysis methods cannot
      distinguish between direct and indirect effects on expression, or calculate the
      relative importance of mRNAs in effecting responses. RESULTS: Application of
      modular regulation analysis to microarray data reveals and quantifies which mRNA
      changes are important for cellular responses. The mRNAs are clustered, and then
      we calculate how perturbations alter each cluster and how strongly those clusters
      affect an output response. The product of these values quantifies how an input
      changes a response through each cluster. Two published datasets are analysed. Two
      mRNA clusters transmit most of the response of yeast doubling time to galactose;
      one contains mainly galactose metabolic genes, and the other a regulatory gene.
      Analysis of the response of yeast relative fitness to 2-deoxy-D-glucose reveals
      that control is distributed between several mRNA clusters, but experimental error
      limits statistical significance.

PMID- 14976029
TI  - Prediction of Saccharomyces cerevisiae protein functional class from functional
      domain composition.
AB  - MOTIVATION: A key goal of genomics is to assign function to genes, especially for
      orphan sequences. RESULTS: We compared the clustered functional domains in the
      SBASE database to each protein sequence using BLASTP. This representation for a
      protein is a vector, where each of the non-zero entries in the vector indicates a
      significant match between the sequence of interest and the SBASE domain. The
      machine learning methods nearest neighbour algorithm (NNA) and support vector
      machines are used for predicting protein functional classes from this
      information. We find that the best results are found using the SBASE-A database
      and the NNA, namely 72% accuracy for 79% coverage. We tested an assigning
      function based on searching for InterPro sequence motifs and by taking the most
      significant BLAST match within the dataset. We applied the functional domain
      composition method to predict the functional class of 2018 currently unclassified
      yeast open reading frames. AVAILABILITY: A program for the prediction method,
      that uses NNA called Functional Class Prediction based on Functional Domains
      (FCPFD) is available and can be obtained by contacting Y.D.Cai at
      y.cai@umist.ac.uk

PMID- 14976030
TI  - TANDEM: matching proteins with tandem mass spectra.
AB  - SUMMARY: Tandem mass spectra obtained from fragmenting peptide ions contain some
      peptide sequence specific information, but often there is not enough information
      to sequence the original peptide completely. Several proprietary software
      applications have been developed to attempt to match the spectra with a list of
      protein sequences that may contain the sequence of the peptide. The application
      TANDEM was written to provide the proteomics research community with a set of
      components that can be used to test new methods and algorithms for performing
      this type of sequence-to-data matching. AVAILABILITY: The source code and
      binaries for this software are available at
      http://www.proteome.ca/opensource.html, for Windows, Linux and Macintosh OSX. The
      source code is made available under the Artistic License, from the authors.

PMID- 14976031
TI  - GeneSyn: a tool for detecting conserved gene order across genomes.
AB  - GeneSyn is a software tool that allows automatic detection of conserved gene
      order from annotated genomes. AVAILABILITY: Available free of charge for
      Unix/Linux/Cygwin platforms at ftp://159.149.110.11/pub/GeneSyn_1.0/
      SUPPLEMENTARY INFORMATION: ftp://159.149.110.11/pub/GeneSyn_1.0/

PMID- 14976032
TI  - Spectral Repeat Finder (SRF): identification of repetitive sequences using
      Fourier transformation.
AB  - MOTIVATION: Repetitive DNA sequences, besides having a variety of regulatory
      functions, are one of the principal causes of genomic instability. Understanding
      their origin and evolution is of fundamental importance for genome studies. The
      identification of repeats and their units helps in deducing the intra-genomic
      dynamics as an important feature of comparative genomics. A major difficulty in
      identification of repeats arises from the fact that the repeat units can be
      either exact or imperfect, in tandem or dispersed, and of unspecified length.
      RESULTS: The Spectral Repeat Finder program circumvents these problems by using a
      discrete Fourier transformation to identify significant periodicities present in
      a sequence. The specific regions of the sequence that contribute to a given
      periodicity are located through a sliding window analysis, and an exact search
      method is then used to find the repetitive units. Efficient and complete
      detection of repeats is provided together with interactive and detailed
      visualization of the spectral analysis of input sequence. We demonstrate the
      utility of our method with various examples that contain previously unannotated
      repeats. A Web server has been developed for convenient access to the automated
      program. AVAILABILITY: The Web server is available at
      http://www.imtech.res.in/raghava/srf and http://www2.imtech.res.in/raghava/srf

PMID- 14976033
TI  - Enhanced homology searching through genome reading frame predetermination.
AB  - MOTIVATION: Many bioinformatic approaches exist for finding novel genes within
      genomic sequence data. Traditionally, homology search-based methods are often the
      first approach employed in determining whether a novel gene exists that is
      similar to a known gene. Unfortunately, distantly related genes or motifs often
      are difficult to find using single query-based homology search algorithms against
      large sequence datasets such as the human genome. Therefore, the motivation
      behind this work was to develop an approach to enhance the sensitivity of
      traditional single query-based homology algorithms against genomic data without
      losing search selectivity. RESULTS: We demonstrate that by searching against a
      genome fragmented into all possible reading frames, the sensitivity of homology
      based searches is enhanced without degrading its selectivity. Using the ETS
      domain, bromodomain and acetyl-CoA acetyltransferase gene as queries, we were
      able to demonstrate that direct protein-protein searches using BLAST2P or FASTA3
      against a human genome segmented among all possible reading frames and translated
      was substantially more sensitive than traditional protein-DNA searches against a
      raw genomic sequence using an application such as TBLAST2N. Receiver operating
      characteristic analysis was employed to demonstrate that the algorithms remained
      selective, while comparisons of the algorithms showed that the protein-protein
      searches were more sensitive in identifying hits. Therefore, through the
      overprediction of reading frames by this method and the increased sensitivity of
      protein-protein based homology search algorithms, a genome can be deeply mined,
      potentially finding hits overlooked by protein-DNA searches against raw genomic
      data.

PMID- 14976034
TI  - galaxie--CGI scripts for sequence identification through automated phylogenetic
      analysis.
AB  - MOTIVATION: The prevalent use of similarity searches like BLAST to identify
      sequences and species implicitly assumes the reference database to be of
      extensive sequence sampling. This is often not the case, restraining the
      correctness of the outcome as a basis for sequence identification. Phylogenetic
      inference outperforms similarity searches in retrieving correct phylogenies and
      consequently sequence identities, and a project was initiated to design a freely
      available script package for sequence identification through automated Web-based
      phylogenetic analysis. RESULTS: Three CGI scripts were designed to facilitate
      qualified sequence identification from a Web interface. Query sequences are
      aligned to pre-made alignments or to alignments made by ClustalW with entries
      retrieved from a BLAST search. The subsequent phylogenetic analysis is based on
      the PHYLIP package for inferring neighbor-joining and parsimony trees. The
      scripts are highly configurable. AVAILABILITY: A service installation and a
      version for local use are found at
      http://andromeda.botany.gu.se/galaxiewelcome.html and http://galaxie.cgb.ki.se

PMID- 14976035
TI  - Caspase-3 has a nonapoptotic function in erythroid maturation.
AB  - Caspase-3 plays a central role in apoptosis. It is also activated in normal
      erythropoiesis, with its activity peaking early during development (erythroid
      colony-forming unit [CFU-E] stage). In the present study, we have reduced the
      expression and subsequent enzymatic activity of caspase-3 by transfection of
      small interfering RNA (siRNA) directed to caspase-3 in a differentiating human
      erythroid culture system. We find that siRNA treatment yields a 50% reduction in
      cells that undergo enucleation with no change in the fraction of cells that
      undergo apoptosis, measured throughout the culture. Furthermore, a substantial
      fraction of treated cells are unable to complete the transition from
      pronormoblasts to basophilic normoblasts. These results demonstrate that caspase
      3 is required for efficient erythropoiesis in this model system.

PMID- 14976036
TI  - Platelet-associated autoantibodies as detected by a solid-phase modified antigen
      capture ELISA test (MACE) are a useful prognostic factor in idiopathic
      thrombocytopenic purpura.
AB  - There were 50 consecutive idiopathic thrombocytopenic purpura (ITP) adult
      patients (platelet count < 100 x 10(9)/L) grouped according to positivity or
      negativity of a solid-phase modified antigen capture enzyme-linked immunosorbent
      assay (ELISA) test (MACE) against glycoprotein IIb/IIIa (GPIIb/IIIa), Ib/IX, and
      IIa/IIIa. Observation started on the day of MACE assay and lasted at least 6
      months. Clinical worsening was defined as the need for starting or modifying
      therapy because of thrombocytopenia lower than 20 x 10(9)/L or patient admission
      due to bleeding symptoms. MACE-positive patients had a higher probability of
      clinical worsening than MACE-negatives (P <.004). The proportion of patients
      worsening was 18 (72%) of 25 among MACE-positives and 8 (32%) of 25 among MACE
      negatives. The median time to clinical worsening was 2.1 months for MACE-positive
      patients and 27.7 months for MACE-negatives. The assay of specific platelet
      autoantibodies may be a useful prognostic tool for the clinical course of ITP.

PMID- 14976037
TI  - Differences in prognostic factors and outcomes in African Americans and whites
      with acute myeloid leukemia.
AB  - Whites have a more favorable prognosis than African Americans for a number of
      cancers. The relationship between race and outcome is less clear in acute myeloid
      leukemia (AML). Using data from 7 Cancer and Leukemia Group B studies initiated
      from 1985 to 1997, we conducted a retrospective cross-sectional analysis of 2570
      patients (270 African American and 2300 white) with de novo AML who received
      induction chemotherapy. African Americans were younger than whites (48 versus 54
      years, P <.001). African Americans also had different cytogenetic risk group
      distributions than whites (P <.001): they were more commonly classified in the
      favorable (23% versus 14%) and unfavorable (31% versus 23%) groups, and less
      commonly classified in the intermediate group (47% versus 63%). African American
      men had a lower complete remission (CR) rate (54%, compared with 64% for white
      men, 65% for white women, and 70% for African American women, P =.001) and a
      worse overall survival compared with all other patients (P =.004), when known
      risk factors are taken into account. African Americans and whites with AML differ
      with respect to important prognostic factors. African American men have worse CR
      rates and overall survival than whites and African American women, and should be
      considered a poor-risk group.

PMID- 14976038
TI  - Hematopoietic stem cell dose correlates with the speed of immune reconstitution
      after stem cell transplantation.
AB  - In the current study, we tested whether higher numbers of hematopoietic stem
      cells correlate with the speed of immune reconstitution in a congenic
      transplantation model (C57BL/Ka, CD45.1, Thy1.1-->C57BL/6, CD45.2, Thy1.2) using
      purified hematopoietic stem cells (c-Kit(+)Thy1.1(low)Lin(-/low)Sca-1(+)). There
      were 3 different doses of stem cells used (400, 1000, and 5000). Phenotypic
      analyses in peripheral blood and spleen demonstrated that higher numbers of
      infused stem cells are associated with more rapid regeneration of T cells
      (CD4(+), CD8(+), naive CD4(+), naive CD8(+)) and B cells at early time points.
      The numbers of T and B cells eventually became equivalent between different dose
      groups at late time points. Production of interleukin-2 and inter-feron-gamma per
      T cell was similar regardless of stem cell dose even when tested at the time when
      there were significant differences in peripheral T-cell counts. The improved
      immune recovery was attributed to a more rapid regeneration of donor-type immune
      cells. Higher numbers of total thymocytes and signal joint T-cell receptor
      excision circles were observed in the higher dose stem cell recipients,
      suggesting that accelerated regeneration of T cells was due to enhanced
      thymopoiesis.

PMID- 14976039
TI  - Modification of hematopoietic stem cell fate by 5aza 2'deoxycytidine and
      trichostatin A.
AB  - Efforts to change the fate of human hematopoietic stem cells (HSCs) and
      progenitor cells (HPCs) in vitro have met with limited success. We hypothesized
      that previously utilized in vitro conditions might result in silencing of genes
      required for the maintenance of primitive HSCs/HPCs. DNA methylation and histone
      deacetylation are components of an epigenetic program that regulates gene
      expression. Using pharmacologic agents in vitro that might possibly interfere
      with DNA methylation and histone deacetylation, we attempted to maintain and
      expand cells with phenotypic and functional characteristics of primitive
      HSCs/HPCs. Human marrow CD34(+) cells were exposed to a cytokine cocktail
      favoring differentiation in combination with 5aza 2'deoxycytidine (5azaD) and
      trichostatin A (TSA), resulting in a significant expansion of a subset of CD34(+)
      cells that possessed phenotypic properties as well as the proliferative potential
      characteristic of primitive HSCs/HPCs. In addition, 5azaD- and TSA-pretreated
      cells but not the CD34(+) cells exposed to cytokines alone retained the ability
      to repopulate immunodeficient mice. Our findings demonstrate that 5azaD and TSA
      can be used to alter the fate of primitive HSCs/HPCs during in vitro culture.

PMID- 14976040
TI  - Loss of MHC class II gene and protein expression in diffuse large B-cell lymphoma
      is related to decreased tumor immunosurveillance and poor patient survival
      regardless of other prognostic factors: a follow-up study from the Leukemia and
      Lymphoma Molecular Profiling Project.
AB  - The Leukemia and Lymphoma Molecular Profiling Project recently published results
      from DNA microarray analyses of 240 diffuse large B-cell lymphomas (DLBCLs). Four
      gene expression "signatures" were identified as correlated with patient outcome,
      including the major histocompatibility complex (MHC) class II genes (eg, HLA-DRA)
      which correlated with better survival. We further analyzed the effects of HLA-DRA
      on survival and correlated gene expression with protein status and tumor
      infiltrating lymphocytes. The 5-year overall survival was 24% in the lowest 10%
      of HLA-DRA expression, 37% in the 10% to 25% group, 50% in the 25% to 50% group,
      and 55% for patients in the highest 50%. Further analysis demonstrated that the
      hazard ratio of death was a nonlinear function of HLA-DRA expression. Adjustment
      for the International Prognostic Index did not alter the impact of HLA-DRA on
      survival. Other MHC class II genes were found to predict survival similarly.
      Microarray HLA-DRA expression correlated with the presence or absence of human
      leukocyte antigen-DR (HLA-DR) protein in 20 of 22 cases assessed. Fewer tumor
      infiltrating CD8(+) T cells were detected in MHC class II-negative cases compared
      with positive cases (2.8% versus 11.0%; P =.001), supporting the hypothesis that
      loss of tumor immunosurveillance has a devastating effect on patient outcome in
      DLBCL.

PMID- 14976041
TI  - Mechanisms associated with IL-6-induced up-regulation of Jak3 and its role in
      monocytic differentiation.
AB  - We report here that Janus kinase 3 (Jak3) is a primary response gene for
      interleukin-6 (IL-6) in macrophage differentiation, and ectopic overexpression of
      Jak3 accelerates monocytic differentiation of normal mouse bone marrow cells
      stimulated with cytokines. Furthermore, we show that incubation of normal mouse
      bone marrow cells with a JAK3-specific inhibitor results in profound inhibition
      of myeloid colony formation in response to granulocyte-macrophage colony
      stimulating factor or the combination of stem cell factor, IL-3, and IL-6. In
      addition, mutagenesis of the Jak3 promoter has revealed that Sp1 binding sites
      within a -67 to -85 element and a signal transducer and activator of
      transcription (Stat) binding site at position -44 to -53 are critical for
      activation of Jak3 transcription in murine M1 myeloid leukemia cells stimulated
      with IL-6. Electrophoretic mobility shift assay (EMSA) analysis has demonstrated
      that Sp1 can bind to the -67 to -85 element and Stat3 can bind to the -44 to -53
      STAT site in IL-6-stimulated M1 cells. Additionally, ectopic overexpression of
      Stat3 enhanced Jak3 promoter activity in M1 cells. This mechanism of activation
      of the murine Jak3 promoter in myeloid cells is distinct from a recently reported
      mechanism of activation of the human JAK3 promoter in activated T cells.

PMID- 14976042
TI  - Efficient gene transfer into rhesus repopulating hematopoietic stem cells using a
      simian immunodeficiency virus-based lentiviral vector system.
AB  - High-titer, HIV-1-based lentiviral vector particles were found to transduce
      cytokine-mobilized rhesus macaque CD34(+) cells and clonogenic progenitors very
      poorly (< 1%), reflecting the postentry restriction in rhesus cells to HIV
      infection. To overcome this barrier, we developed a simian immunodeficiency virus
      (SIV)-based vector system. A single exposure to a low concentration of
      amphotropic pseudotyped SIV vector particles encoding the green fluorescent
      protein (GFP) resulted in gene transfer into 68% +/- 1% of rhesus bulk CD34(+)
      cells and 75% +/- 1% of clonogenic progenitors. Polymerase chain reaction (PCR)
      analysis of DNA from individual hematopoietic colonies confirmed these relative
      transduction efficiencies. To evaluate SIV vector-mediated stem cell gene
      transfer in vivo, 3 rhesus macaques underwent transplantation with transduced,
      autologous cytokine-mobilized peripheral blood CD34(+) cells following
      myeloablative conditioning. Hematopoietic reconstitution was rapid, and an
      average of 18% +/- 8% and 15% +/- 7% GFP-positive granulocytes and monocytes,
      respectively, were observed 4 to 6 months after transplantation, consistent with
      the average vector copy number of 0.19 +/- 0.05 in peripheral blood leukocytes as
      determined by real-time PCR. Vector insertion site analysis demonstrated
      polyclonal reconstitution with vector-containing cells. SIV vectors appear
      promising for evaluating gene therapy approaches in nonhuman primate models.

PMID- 14976043
TI  - Epitope mapping of ADAMTS13 autoantibodies in acquired thrombotic
      thrombocytopenic purpura.
AB  - Severe deficiency of the von Willebrand factor (VWF)-cleaving protease ADAMTS13
      can lead to thrombotic thrombocytopenic purpura (TTP), a disease associated with
      the widespread formation of platelet-rich thrombi in many organs. Autoantibodies
      that inactivate ADAMTS13 are the most frequent cause of acquired TTP. Little is
      known about epitope specificity and reactivity of anti-ADAMTS13 antibodies. In
      this study, a series of ADAMTS13 domains were expressed in Escherichia coli, and
      the reactivity of purified recombinant fragments with anti-ADAMTS13 auto
      antibodies from 25 patients with severe ADAMTS13 deficiency was evaluated in
      vitro. All TTP plasmas contained antibodies directed against the cysteine-rich
      spacer (cys-rich/spacer) domain of ADAMTS13. In the plasma of 3 patients,
      antibodies were detected that reacted exclusively with the cys-rich/spacer
      domain, underscoring the importance of this region for functional activity of
      ADAMTS13. In 64% of the plasmas, antibodies reacted with the 2 CUB domains, and
      in 56% they reacted with the isolated first thrombospondin type 1 (TSP-1) repeat
      and with the compound fragment consisting of the catalytic, the disintegrin-like,
      and the TSP1-1 domain. Less frequently, in 28% of the plasmas, antibodies reacted
      with the TSP1 repeats 2 to 8. Unexpectedly, antibodies reacted with the
      propeptide region in 20% of the plasmas. In conclusion, this study shows that
      even though anti-ADAMTS13 autoantibodies react with multiple domains of the
      protease, the cys-rich/spacer domain is consistently involved in antibody
      reactivity.

PMID- 14976044
TI  - The occurrence of graft-versus-host disease is the major predictive factor for
      response to donor lymphocyte infusions in multiple myeloma.
AB  - The graft-versus-myeloma (GVM) effect of donor lymphocyte infusions (DLIs) is
      well established. We now report the outcome of DLI in 54 patients with relapsed
      myeloma following allogeneic transplantation. Twenty-eight patients (52%)
      responded, 19 patients (35%) with a partial response and 9 patients (17%) with a
      complete response. Progression-free and overall survival were 19 and 23 months,
      respectively. We found that acute and chronic graft-versus-host disease (GVHD)
      observed in 57% and 47% of patients, respectively, following DLI were the
      strongest predictors for response. This suggests that targets for GVHD and GVM
      are identical. In a subgroup analysis, deletion of chromosome 13, as determined
      by double-color fluorescence in situ hybridization (FISH), had no impact on
      outcome, indicating that these patients are candidates for early allogeneic
      transplantation followed by DLI, in case of insufficient response.

PMID- 14976045
TI  - Evidence for anti-inflammatory activity of statins and PPARalpha activators in
      human C-reactive protein transgenic mice in vivo and in cultured human
      hepatocytes in vitro.
AB  - Inflammatory processes, aside from cholesterol, play a central role in
      atherogenesis. Human C-reactive protein (huCRP) signals systemic inflammation and
      independently predicts future cardiovascular risk. Cholesterol-lowering statins
      reduce atherosclerosis and plasma huCRP levels. Evidence is sought for a direct
      anti-inflammatory statin effect in vivo, independent of effects on plasma
      cholesterol and atherogenesis. The effect of atorvastatin and simvastatin on
      huCRP expression was studied in nonatherosclerotic huCRP transgenic mice and
      compared with another class of hypolipidemic drugs, peroxisome proliferator
      activated receptor-alpha (PPARalpha) activators, notably fenofibrate and Wy14643.
      Like statins, PPARalpha activators combine antiatherosclerotic properties with
      huCRP-lowering effects. Dietary treatment with statins or PPARalpha activators
      decreased basal and interleukin-1beta (IL-1beta)-induced plasma huCRP levels
      independently of cholesterol lowering. These direct anti-inflammatory in vivo
      effects occurred at the transcriptional level and could be confirmed in cultured
      human liver slices and in human hepatoma cells transiently transfected with a
      huCRP promoter-driven luciferase reporter. A molecular rationale for the
      suppression of IL-1-induced huCRP transcription is provided by showing that
      statins and PPARalpha activators up-regulate IkappaBalpha protein expression.
      This results in a reduced nuclear translocation of p50-nuclear factor kappa B
      (NFkappaB) and thereby decreased amounts of nuclear p50-NFkappaB approximately
      CCAAT/enhancer binding protein beta (C/EBPbeta) complexes, which determine the
      huCRP transcription rate. Our results provide conclusive evidence for a direct
      suppressive effect of statins and PPARalpha activators on huCRP expression
      independent of cholesterol lowering and atherogenesis.

PMID- 14976046
TI  - Prolonged treatment with rituximab in patients with follicular lymphoma
      significantly increases event-free survival and response duration compared with
      the standard weekly x 4 schedule.
AB  - The potential benefits of extended rituximab treatment have been investigated in
      a randomized trial comparing the standard schedule with prolonged treatment in
      202 patients with newly diagnosed or refractory/relapsed follicular lymphoma
      (FL). All patients received standard treatment (rituximab 375 mg/m(2) weekly x
      4). In 185 evaluable patients, the overall response rate was 67% in chemotherapy
      naive patients and 46% in pretreated cases (P <.01). Patients responding or with
      stable disease at week 12 (n = 151) were randomized to no further treatment or
      prolonged rituximab administration (375 mg/m(2) every 2 months for 4 times). At a
      median follow-up of 35 months, the median event-free survival (EFS) was 12 months
      in the no further treatment versus 23 months in the prolonged treatment arm (P
      =.02), the difference being particularly notable in chemotherapy-naive patients
      (19 vs 36 months; P =.009) and in patients responding to induction treatment (16
      vs 36 months; P =.004). The number of t(14;18)-positive cells in peripheral blood
      (P =.0035) and in bone marrow (P =.0052) at baseline was predictive for clinical
      response. Circulating normal B lymphocytes and immunoglobulin M (IgM) plasma
      levels decreased for a significantly longer time after prolonged treatment, but
      the incidence of adverse events was not increased. In patients with FL, the
      administration of 4 additional doses of rituximab at 8-week intervals
      significantly improves the EFS.

PMID- 14976047
TI  - Imatinib mesylate (STI571) decreases the vascular endothelial growth factor
      plasma concentration in patients with chronic myeloid leukemia.
AB  - Increased angiogenesis in bone marrow (BM) is one of the characteristics of
      chronic myeloid leukemia (CML), a clonal myeloproliferative disorder that
      expresses a chimeric Bcr/Abl protein. Recently, the therapeutic strategy in CML
      has been totally modified with the development of a new drug: imatinib mesylate
      (STI571), a specific inhibitor of Bcr/Abl tyrosine kinase activity. The aim of
      our study was to determine, in patients with CML, the capacity of imatinib
      mesylate to modulate one of the most potent regulators of angiogenesis, the
      vascular endothelial growth factor (VEGF). In newly diagnosed CML, we observed
      significantly increased VEGF secretion by CML BM cells and significantly
      increased VEGF plasma concentrations. We showed that low plasma VEGF
      concentrations could be one of the characteristics of complete cytogenetic
      remission. To understand the molecular mechanisms leading to the inhibition of
      VEGF production by imatinib, we focused our experiments on the human cell line
      K562, which is Bcr/Abl positive. We demonstrated that imatinib inhibits VEGF gene
      transcription by targeting the Sp1 and Sp3 transcription factors. Taken together,
      our results highlight the potential prognostic value of VEGF concentrations in
      evaluating the evolution of CML patients treated with imatinib.

PMID- 14976048
TI  - Phosphoinositide 3-kinase signaling is essential for ABL oncogene-mediated
      transformation of B-lineage cells.
AB  - BCR-ABL and v-ABL are oncogenic forms of the Abl tyrosine kinase that can cause
      leukemias in mice and humans. ABL oncogenes trigger multiple signaling pathways
      whose contribution to transformation varies among cell types. Activation of
      phosphoinositide 3-kinase (PI3K) is essential for ABL-dependent proliferation and
      survival in some cell types, and global PI3K inhibitors can enhance the
      antileukemia effects of the Abl kinase inhibitor imatinib. Although a significant
      fraction of BCR-ABL-induced human leukemias are of B-cell origin, little is known
      about PI3K signaling mechanisms in B-lineage cells transformed by ABL oncogenes.
      Here we show that activation of class I(A) PI3K and downstream inactivation of
      FOXO transcription factors are essential for survival of murine pro/pre-B cells
      transformed by v-ABL or BCR-ABL. In addition, analysis of mice lacking individual
      PI3K genes indicates that products of the Pik3r1 gene contribute to
      transformation efficiency by BCR-ABL. These findings establish a role for PI3K
      signaling in B-lineage transformation by ABL oncogenes.

PMID- 14976049
TI  - SOCS1 and SHP1 hypermethylation in multiple myeloma: implications for epigenetic
      activation of the Jak/STAT pathway.
AB  - SOCS1 and SHP1 negatively regulate the Janus kinase/signal transducer and
      activator of transcription (Jak/STAT) signaling pathway. The role of promoter
      hypermethylation leading to epigenetic inactivation of SOCS1 and SHP1 in myeloma
      was investigated. The methylation-specific polymerase chain reaction (MSP) was
      used to define SOCS1 and SHP1 methylation in 34 diagnostic myeloma samples. For
      SOCS1, MSP primers 3' to the translation start site were unreliable and gave
      positive results in normal controls. However, primers in the 5' promoter region
      were specific, although no myeloma samples showed methylation. For SHP1, 27 of 34
      (79.4%) myeloma samples showed SHP1 hypermethylation. The biologic significance
      of SHP1 methylation was investigated in the U266 human myeloma line. U266
      contained completely methylated SHP1. Furthermore, there was constitutive STAT3
      phosphorylation. Treatment with 5-azacytidine led to progressive demethylation of
      SHP1 on days 2 to 5, with consequent increasing reexpression of SHP1 as shown by
      reverse transcription-polymerase chain reaction (RT-PCR). Concomitant with
      increasing SHP1, a parallel down-regulation of phosphorylated STAT3 occurred, so
      that by day 5 phosphorylated STAT3 was barely detectable. The overall survivals
      of patients with and without SHP1 methylation were similar. SHP1 methylation
      leading to epigenetic activation of the Jak/STAT pathway might have a tentative
      role in the pathogenesis of myeloma, which should be further confirmed by
      functional studies in primary myeloma samples.

PMID- 14976050
TI  - Hemangiopoietin, a novel human growth factor for the primitive cells of both
      hematopoietic and endothelial cell lineages.
AB  - The cells of hematopoietic and vascular endothelial cell lineages are believed to
      share a common precursor, termed hemangioblast. However, the existence of a
      growth factor acting relatively specifically on hemangioblasts remains unclear.
      Here we report the identification of hemangiopoietin (HAPO), a novel growth
      factor acting on both hematopoietic and endothelial cell lineages. In vitro in
      the human system, recombinant human HAPO (rhHAPO) significantly stimulated the
      proliferation and hematopoietic and/or endothelial differentiation of human bone
      marrow mononuclear cells and of purified CD34+, CD133+, kinase domain receptor
      positive (KDR+), or CD34+/KDR+ cell populations. In the murine system, rhHAPO
      stimulated the proliferation of long-term culture-initiating cells (LTC-ICs) as
      well as CD34+ and stem cell antigen-1 (Sca-1+) cell subsets. In vivo,
      subcutaneous injection of rhHAPO into normal mice resulted in a significant
      increase in bone marrow hematopoietic cells. Furthermore, irradiated mice
      injected with rhHAPO had an enhanced survival rate and accelerated hematopoiesis.
      Our data suggest that HAPO is a novel growth factor acting on the primitive cells
      of both hematopoietic and endothelial cell lineages and that HAPO may have a
      clinical potential in the treatment of various cytopenias and radiation injury
      and in the expansion of hematopoietic and endothelial stem/progenitor cells.

PMID- 14976051
TI  - The interferon regulatory factor ICSBP/IRF-8 in combination with PU.1 up
      regulates expression of tumor suppressor p15(Ink4b) in murine myeloid cells.
AB  - CDKN2B (INK4B), which encodes the cyclin-dependent kinase inhibitor p15(INK4b),
      is up-regulated by many cytokines found in hematopoietic environments in vivo. In
      human acute myeloid leukemias (AMLs), it is inactivated with high frequency. To
      gain insight into the regulatory pathways leading to the normal activation of
      p15(Ink4b) expression, we examined interferon beta (IFNbeta)-induced
      transcription. Using reporter gene assays in murine myeloid cells M1, we
      determined that a 328-bp fragment, located 117 to 443 bp upstream of the
      translation initiation site, was sufficient to activate transcription. Both the
      interferon consensus sequence-binding protein/interferon regulatory factor 8
      (ICSBP/IRF-8) and PU.1 were able to increase transcription from this region. It
      was determined that both ICSBP and PU.1 must bind to DNA to form a stable
      PU.1/ICSBP binding complex. Interestingly, introduction of the ICSBP into ICSBP
      null Tot2 cells led to a significant increase in p15(Ink4b) RNA expression. This
      regulation of the Ink4b promoter is apparently myeloid specific because both
      ICSBP and PU.1 are myeloid commitment factors. Importantly, this provides a
      mechanism to explain in part the tumor suppressor activity of ICSBP, since ICSBP
      deficient mice develop a chronic myelogenous leukemia (CML)-like disease and a
      high percentage of human AML and CML lack ICSBP transcripts.

PMID- 14976052
TI  - Human potassium chloride cotransporter 1 (SLC12A4) promoter is regulated by AP-2
      and contains a functional downstream promoter element.
AB  - Most K-Cl cotransport in the erythrocyte is attributed to potassium chloride
      cotransporter 1 (KCC1). K-Cl cotransport is elevated in sickle erythrocytes, and
      the KCC1 gene has been proposed as a modifier gene in sickle cell disease. To
      provide insight into our understanding of the regulation of the human KCC1 gene,
      we mapped the 5' end of the KCC1 cDNA, cloned the corresponding genomic DNA, and
      identified the KCC1 gene promoter. The core promoter lacks a TATA box and is
      composed of an initiator element (InR) and a downstream promoter element (DPE), a
      combination found primarily in Drosophila gene promoters and rarely observed in
      mammalian gene promoters. Mutational analyses demonstrated that both the InR and
      DPE sites were critical for full promoter activity. In vitro DNase I
      footprinting, electrophoretic mobility shift assays, and reporter gene assays
      identified functional AP-2 and Sp1 sites in this region. The KCC1 promoter was
      transactivated by forced expression of AP-2 in heterologous cells. Sequences
      encoding the InR, DPE, AP-2, and Sp1 sites were 100% conserved between human and
      murine KCC1 genes. In vivo studies using chromatin immunoprecipitation assays
      with antihistone H3 and antihistone H4 antibodies demonstrated hyperacetylation
      of this core promoter region.

PMID- 14976053
TI  - Induction of antigen-specific tolerance to bone marrow allografts with CD4+CD25+
      T lymphocytes.
AB  - Thymus-derived regulatory T lymphocytes of CD4(+)CD25(+) phenotype regulate a
      large variety of beneficial and deleterious immune responses and can inhibit
      lethal graft-versus-host disease in rodents. In vitro, CD4(+)CD25(+) T cells
      require specific major histocompatibility complex (MHC)/peptide ligands for their
      activation, but once activated they act in an antigen-nonspecific manner. In
      vivo, regulatory T cells are also activated in an antigen-specific fashion, but
      nothing is known about antigen specificity of their suppressor-effector function.
      Here we show that CD4(+)CD25(+) regulatory T lymphocytes isolated from naive mice
      and activated in vitro with allogeneic antigen-presenting cells (APCs) induced
      specific long-term tolerance to bone marrow grafts disparate for major and minor
      histocompatibility antigens; whereas "target" bone marrow was protected, third
      party bone marrow was rejected. Importantly, in mice injected with a mix of
      target and third-party bone marrows, protection and rejection processes took
      place simultaneously. These results indicate that CD4(+)CD25(+) regulatory T
      cells can act in an antigen-specific manner in vivo. Our results suggest that
      CD4(+)CD25(+) regulatory T cells could in the future be used in clinical settings
      to induce specific immunosuppression.

PMID- 14976054
TI  - High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple
      sclerosis revealed by novel flow cytometric assay.
AB  - Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central
      nervous system (CNS) with features suggestive of T-cell-mediated pathology. Most
      prior reports have focused on CD4(+) T cells with the underlying assumption that
      MS is predominantly a CD4(+) T helper 1 (Th1)-mediated disease. In this report,
      we used a novel flow cytometric approach to evaluate autoreactive T-cell
      responses against a large variety of neuroantigenic targets. We found that both
      CD4(+) and CD8(+) T cells targeted against several CNS autoantigens were widely
      prevalent in patients with MS and healthy individuals. Whereas the distribution
      of CD4(+) responses was similar in different groups, patients with relapsing
      remitting MS showed a higher proportion of CNS-specific CD8(+) responses.
      Autoreactive CD4(+) T cells from patients with MS exhibited a more differentiated
      Th1 phenotype compared with healthy subjects. Similarly, CNS-specific CD8(+) T
      cell responses from patients with MS were functionally distinct from those in
      healthy individuals. Collectively, these studies reveal the high prevalence of
      class I-restricted autoreactive CD8(+) T-cell responses in MS that has been
      underappreciated thus far. The results emphasize the need to evaluate both CD4(+)
      and CD8(+) T-cell responses in MS and to make both subsets a consideration in the
      development of novel therapeutic strategies.

PMID- 14976055
TI  - A single recombinant anti-RhD IgG prevents RhD immunization: association of RhD
      positive red blood cell clearance rate with polymorphisms in the FcgammaRIIA and
      FcgammaIIIA genes.
AB  - A single recombinant immunoglobulin G1 (IgG1) anti-RhD antibody (MonoRho) was
      compared with a currently used polyclonal anti-RhD product (Rhophylac) in a phase
      1 study for safety, efficacy of Rhesus D (RhD)-positive red blood cell (RBC)
      clearance, and prevention of RhD immunization in RhD-negative men challenged with
      15 mL RhD-positive RBCs. Both the polyclonal product and recombinant anti-RhD
      effectively cleared RhD-positive RBCs after intravenous and intramuscular
      injection. The recombinant anti-RhD demonstrated a slower clearance rate compared
      with the polyclonal anti-RhD. There was no dose response, and there was
      considerable variation among subjects who received the same dose of recombinant
      anti-RhD. Interestingly, RhD-positive RBC clearance rates were strongly
      associated with Fcgamma receptor IIA (FcgammaRIIA) and FcgammaIIIA but not with
      FcgammaIIIB polymorphisms. Subjects homozygous for FcgammaRIIA-131H or
      FcgammaRIIIA-158V allotypes showed a faster clearance rate compared with both the
      heterozygote and the corresponding alternative homozygote allotypes. A similar
      but less marked trend was seen for the polyclonal anti-RhD. Despite the variation
      in clearance rates there was no evidence of anti-RhD alloantibodies in any of the
      subjects at +6 months after the RBC challenge.

PMID- 14976056
TI  - The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon
      stimulation from endothelial cell Weibel-Palade bodies.
AB  - The angiopoietins Ang-1 and Ang-2 have been identified as ligands with opposing
      functions of the receptor tyrosine kinase Tie-2 regulating endothelial cell
      survival and vascular maturation. Ang-1 acts in a paracrine agonistic manner,
      whereas Ang-2 appears to act primarily as an autocrine antagonistic regulator. To
      shed further light on the complexity of autocrine/paracrine
      agonistic/antagonistic functions of the angiopoietin/Tie-2 system, we have
      studied Ang-2 synthesis and secretion in different populations of wild-type and
      retrovirally Ang-2-transduced endothelial cells. Endogenous and overexpressed
      endothelial cell Ang-2 is expressed in a characteristic granular pattern
      indicative of a cytoplasmic storage granule. Light and electron microscopic
      double staining revealed Ang-2 colocalization with von Willebrand factor,
      identifying Ang-2 as a Weibel-Palade body molecule. Costaining with P-selectin
      showed that storage of Ang-2 and P-selectin in Weibel-Palade bodies is mutually
      exclusive. Stored Ang-2 has a long half-life of more than 18 hours and can be
      secreted within minutes of stimulation (eg, by phorbol 12-myristate 13-acetate
      [PMA], thrombin, and histamine). Collectively, the identification of Ang-2 as a
      stored, rapidly available molecule in endothelial cells strongly suggests
      functions of the angiopoietin/Tie-2 system beyond the established roles during
      angiogenesis likely to be involved in rapid vascular homeostatic reactions such
      as inflammation and coagulation.

PMID- 14976057
TI  - Impaired APC cofactor activity of factor V plays a major role in the APC
      resistance associated with the factor V Leiden (R506Q) and R2 (H1299R) mutations.
AB  - Activated protein C (APC) resistance is a major risk factor for venous
      thrombosis. Factor V (FV) gene mutations like FV(Leiden) (R506Q) and FV(R2)
      (H1299R) may cause APC resistance either by reducing the susceptibility of FVa to
      APC-mediated inactivation or by interfering with the cofactor activity of FV in
      APC-catalyzed FVIIIa inactivation. We quantified the APC cofactor activity
      expressed by FV(Leiden) and FV(R2) and determined the relative contributions of
      reduced susceptibility and impaired APC cofactor activity to the APC resistance
      associated with these mutations. Plasmas containing varying concentrations of
      normal FV, FV(Leiden), or FV(R2) were assayed with an APC resistance assay that
      specifically measures the APC cofactor activity of FV in FVIIIa inactivation, and
      with the activated partial thromboplastin time (aPTT)-based assay, which probes
      both the susceptibility and APC cofactor components. FV(R2) expressed 73% of the
      APC cofactor activity of normal FV, whereas FV(Leiden) exhibited no cofactor
      activity in FVIIIa inactivation. Poor susceptibility to APC and impaired APC
      cofactor activity contributed equally to FV(Leiden)-associated APC resistance,
      whereas FV(R2)-associated APC resistance was entirely due to the reduced APC
      cofactor activity of FV(R2). Thrombin generation assays confirmed the importance
      of the anticoagulant activity of FV and indicated that FV(Leiden) homozygotes are
      exposed to a higher thrombotic risk than heterozygotes because their plasma lacks
      normal FV acting as an anticoagulant protein.

PMID- 14976058
TI  - Plasticity of endothelial cells: rapid dedifferentiation of freshly isolated high
      endothelial venule endothelial cells outside the lymphoid tissue
      microenvironment.
AB  - Endothelial cells display remarkable heterogeneity in different organs and
      vascular beds. Although many studies suggest that tissues "speak" to endothelial
      cells, endothelial cell diversity remains poorly characterized at the molecular
      level. Here, we describe a novel strategy to characterize tissue-specific
      endothelial cell phenotypes and to identify endothelial cell genes that are under
      the control of the local microenvironment. By comparing post-capillary high
      endothelial venule endothelial cells (HEVECs), freshly isolated from human
      tonsils without any cell culture step, with HEVECs cultured for 2 days, we found
      that HEVECs rapidly lost their specialized characteristics when isolated from the
      lymphoid tissue microenvironment. Striking changes occurred as early as after 48
      hours, with complete loss of the postcapillary venule-specific Duffy antigen
      receptor for chemokines (DARCs) and the HEV-specific fucosyltransferase Fuc-TVII.
      DNA microarray analysis identified several other candidate HEV genes that were
      rapidly down-regulated ex vivo, including type XV collagen, which we
      characterized as a novel, abundant HEV transcript in situ. Together, our results
      demonstrate that blood vessel type-specific and tissue-specific characteristics
      of endothelial cells are under the control of their microenvironment. Therefore,
      even short-term primary cultures of human endothelial cells may not adequately
      mimic the differentiated endothelial cell phenotypes existing in vivo.

PMID- 14976059
TI  - Myeloid-biased hematopoietic stem cells have extensive self-renewal capacity but
      generate diminished lymphoid progeny with impaired IL-7 responsiveness.
AB  - The adult hematopoietic stem cell (HSC) compartment contains a substantial
      population of lineage-biased (Lin-bi) HSCs. Lin-bi HSCs generate cells of all
      hematopoietic lineages, albeit with skewed ratios of lymphoid to myeloid cells.
      The biased ratios are stable through serial transplantation, demonstrating that
      lineage bias is an inherent function of the HSCs. To define the mechanisms that
      cause lineage bias, the developmental potential of myeloid-biased (My-bi) HSCs
      was characterized. In serial transplantation experiments, My-bi HSCs contributed
      significantly longer to repopulation than other types of HSCs. The long lifespan
      indicates that My-bi HSCs are important for the persistence of HSC function
      throughout life. My-bi HSCs produce normal levels of myeloid precursors but
      reduced levels of precursors for the T- and B- lymphocyte lineages. Gene array
      analysis suggested that the lymphoid progeny of My-bi HSCs express lowered levels
      of interleukin-7 (IL-7) receptor. Indeed, the progeny derived from My-bi HSCs
      failed to respond to IL-7 in vitro. Thus, My-bi HSCs are programmed for
      diminished lymphopoiesis through a mechanism that involves a blunted response of
      its progeny to the central lymphokine IL-7. The data demonstrate that epigenetic
      regulation on the level of the HSCs can directly affect the number, composition,
      and function of the mature progeny.

PMID- 14976060
TI  - Deletion of the alternatively spliced fibronectin EIIIA domain in mice reduces
      atherosclerosis.
AB  - The alternatively spliced and highly conserved EIIIA domain of fibronectin (FN)
      is included in most FN of the extracellular matrix in embryos. In adults, both
      extracellular matrix and plasma FN essentially lack EIIIA. In diverse
      inflammatory situations however, EIIIA is specifically included by regulated RNA
      splicing. In atherosclerotic lesions, FN, including the EIIIA domain (EIIIA-FN),
      is abundant, whereas FN in the flanking vessel wall lacks EIIIA. Lesional EIIIA
      FN is localized with endothelial cells and macrophage foam cells. To directly
      test the function of EIIIA-FN, we generated EIIIA-null (EIIIA(-/-)) mice that
      lack the EIIIA exon and crossed them with apolipoprotein E (ApoE)-null (ApoE(-/
      )) mice that develop arterial wall lesions. Compared with ApoE(-/-) controls,
      EIIIA(-/-)ApoE(-/-) mice had significantly smaller lesions throughout the aortic
      tree. EIIIA-FN was increased in ApoE(-/-) plasma, and total plasma cholesterol
      was reduced in EIIIA(-/-)ApoE(-/-) mice, specifically in large lipoprotein
      particles, suggesting a functional role for plasma EIIIA-FN. To assess a role for
      macrophage EIIIA-FN in the vessel wall, we conducted in vitro foam cell assays.
      EIIIA(-/-)ApoE(-/-) macrophages accumulated significantly less intracellular
      lipid than control ApoE(-/-) cells. These results provide genetic evidence that
      suggests roles for EIIIA-FN in plasma lipoprotein metabolism and in foam cell
      formation.

PMID- 14976061
TI  - Expression of KIR2DL1 on the entire NK cell population: a possible novel
      immunodeficiency syndrome.

PMID- 14976062
TI  - Imatinib mesylate impairs Flt3L-mediated dendritic cell expansion and antitumor
      effects in vivo.

PMID- 14976063
TI  - Prophylaxis with defibrotide prevents veno-occlusive disease in stem cell
      transplantation after gemtuzumab ozogamicin exposure.

PMID- 14976064
TI  - CD38 on B-cell chronic lymphocytic leukemia cells has higher expression in lymph
      nodes than in peripheral blood or bone marrow.

PMID- 14976065
TI  - Efficacy of alemtuzumab treatment for refractory T-cell large granular
      lymphocytic leukemia.

PMID- 14976066
TI  - Rituximab administration following autologous stem cell transplantation for
      multiple myeloma is associated with severe IgM deficiency.

PMID- 14976067
TI  - Thrombophilia as a common predisposing factor in pseudotumor cerebri.

PMID- 14976068
TI  - IVIg-mediated amelioration of murine ITP via FcgammaRIIb is not necessarily
      independent of SHIP-1 and SHP-1 activity.

PMID- 14976069
TI  - Asymmetrical involvement of frontal lobes in social reasoning.
AB  - The frontal lobes are widely implicated in logical reasoning. Recent neuroimaging
      studies suggest that frontal lobe involvement in reasoning is asymmetric (L>R)
      and increases with the presence of familiar, meaningful content in the reasoning
      situation. However, neuroimaging data can only provide sufficiency criteria. To
      determine the necessity of prefrontal involvement in logical reasoning, we tested
      19 patients with focal frontal lobe lesions and 19 age- and education-matched
      normal controls on the Wason Card Selection Task, while manipulating social
      knowledge. Patients and controls performed equivalently on the arbitrary rule
      condition. Normal controls showed the expected improvement in the social
      knowledge conditions, but frontal lobe patients failed to show this facilitation
      in performance. Furthermore, left hemisphere patients were more affected than
      right hemisphere patients, suggesting that frontal lobe involvement in reasoning
      is asymmetric (L>R) and necessary for reasoning about social situations.

PMID- 14976070
TI  - How do strength, sensation, spasticity and joint individuation relate to the
      reaching deficits of people with chronic hemiparesis?
AB  - Hemiparetic subjects present with movement deficits including weakness,
      spasticity and an inability to isolate movement to one or a few joints. Voluntary
      attempts to move a single joint often result in excessive motion at adjacent
      joints. We investigated whether the inability to individuate joint movements is
      associated with deficits in functional reaching. Controls and hemiparetic
      subjects performed two different reaching movements and three individuated arm
      movements, all in the parasagittal plane. The reaching movements were a sagittal
      'reach up' (shoulder flexion and elbow flexion) and 'reach out' (shoulder flexion
      and elbow extension). Joint individuation was assessed by getting each subject to
      perform an isolated flexion-extension movement at each of the shoulder, elbow and
      wrist joints. In addition, we measured strength, muscle tone and sensation using
      standard clinical instruments. Hemiparetic subjects showed varying degrees of
      impairment when performing reaching movements and individuated joint movements.
      Reaching impairments (hand path curvature, velocity) were worse in the reach out
      versus the reach up condition. Typical joint individuation abnormalities were
      excessive flexion of joints that should have been held fixed during movement of
      the instructed joint. Hemiparetic subjects tended to produce concurrent flexion
      motions of shoulder and elbow joints when attempting any movement, one
      explanation for why they were better at the 'reach up' than the 'reach out' task.
      Hierarchical regression analysis showed that impaired joint individuation
      explained most of the variance in the reach path curvature and end point error;
      strength explained most of the variance in reaching velocity. Sensation also
      contributed significantly, but spasticity and strength were not significant in
      the model. We conclude that the deficit in joint individuation reflects a
      fundamental motor control problem that largely explains some aspects of voluntary
      reaching deficits of hemiparetic subjects.

PMID- 14976071
TI  - Human cells from cloned embryos in research and therapy.

PMID- 14976072
TI  - Patients' expectations of consultations.

PMID- 14976073
TI  - Making amends for negligence.

PMID- 14976074
TI  - No time to train the surgeons.

PMID- 14976075
TI  - Prognosis after cochlear implantation.

PMID- 14976076
TI  - Korean scientists clone 30 human embryos.

PMID- 14976079
TI  - 100 000 children die needlessly from cancer every year.

PMID- 14976080
TI  - Charity makes cancer gene freely available across Europe.

PMID- 14976083
TI  - Officials warn of looming humanitarian crisis in Sudan.

PMID- 14976085
TI  - Pregnant women should have two scans, Scottish agency says.

PMID- 14976087
TI  - Loophole to be closed on recognition of qualifications.

PMID- 14976088
TI  - New HIV cases in England and Wales increase by 20% in past year.

PMID- 14976089
TI  - Australia makes concessions on drug approvals after US pressure.

PMID- 14976090
TI  - Mothers suspected of killing their babies might be dealt with outside criminal
      system.

PMID- 14976092
TI  - Surgeons introduce computer assisted, minimally invasive surgery for hip
      replacement.

PMID- 14976093
TI  - FAO/WHO meeting warns of contamination of powdered infant formula.

PMID- 14976094
TI  - WHO warns that avian flu could still be in the environment.

PMID- 14976097
TI  - Bearing witness.

PMID- 14976098
TI  - Systematic review of prevalence of aspirin induced asthma and its implications
      for clinical practice.
AB  - OBJECTIVE: To reassess the prevalence of aspirin induced asthma and other issues
      related to the syndrome. DATA SOURCES: Biosis, SciSearch (1990 to March 2002),
      Embase (1974 to March 2002), Medline (1966 to March 2002), Toxline, Derwent Drug
      File (1964 to March 2002), Conference Papers Index and Inside Conferences, Int'l
      Pharmaceutical Abstracts, Pharma-Online (1978 to March 2002). SELECTION CRITERIA:
      Study type, patient population, and outcome measures. Review was restricted to
      respiratory responses to analgesics available without prescription. RESULTS: The
      prevalence of aspirin induced asthma was highest when determined by oral
      provocation testing (adults 21%, 95% confidence interval 14% to 29%; children 5%,
      0% to 14%) than by verbal history (adults 3%, 2% to 4%; children 2%, 1% to 3%).
      Cross sensitivity to doses of over the counter non-steroidal anti-inflammatory
      drugs was present in most patients with aspirin induced asthma: ibuprofen, 98%;
      naproxen, 100%; and diclofenac, 93%. The incidence of cross sensitivity to
      paracetamol among such patients was only 7%. CONCLUSIONS: Aspirin induced asthma
      in adults is more prevalent than previously suggested. When there is a clinical
      necessity to use aspirin or a non-steroidal anti-inflammatory drug and there is
      uncertainty about safety, oral provocation testing should be performed.

PMID- 14976099
TI  - Training for patients in a randomised controlled trial of self management of
      warfarin treatment.

PMID- 14976100
TI  - Coeliac disease and schizophrenia: population based case control study with
      linkage of Danish national registers.

PMID- 14976101
TI  - How strong is the evidence of a link between environmental chemicals and adverse
      effects on human reproductive health?

PMID- 14976102
TI  - Bradycardia in acute haemorrhage.

PMID- 14976103
TI  - Nicotine replacement therapy.

PMID- 14976104
TI  - The future of clinical negligence litigation?

PMID- 14976105
TI  - What's the problem?

PMID- 14976106
TI  - Sickness certification system in the United Kingdom: medical certificates are
      challenging but essential part of job.

PMID- 14976107
TI  - Sickness certification system in the United Kingdom: Department for Work and
      Pensions is trying to address challenges.

PMID- 14976108
TI  - Sickness certification system in the United Kingdom: maybe charging for
      certificates clarifies matters.

PMID- 14976109
TI  - Sickness certification system in the United Kingdom: doctors are indeed agents of
      social control.

PMID- 14976110
TI  - Public involvement in health care: every voice counts, not just that of patients.

PMID- 14976111
TI  - Public involvement in health care: public involvement is needed at highest level.

PMID- 14976112
TI  - Public involvement in health care: process needs to be transparent and open.

PMID- 14976113
TI  - Public involvement in health care: Some things do count.

PMID- 14976114
TI  - Health needs of women who have sex with women: maybe new subspecialty is needed.

PMID- 14976115
TI  - Health needs of women who have sex with women: methodological assumptions
      underlying conclusions should have been questioned.

PMID- 14976116
TI  - NHS Modernisation Agency's way to improve health care.

PMID- 14976117
TI  - Health needs of women who have sex with women: evidence is lacking that women who
      have sex with women are high risk group for cancer.

PMID- 14976118
TI  - Health needs of women who have sex with women: cervical screening is offered
      without asking for sexual preferences.

PMID- 14976119
TI  - Health risks of overseas travel: ignorance and complacency prevail about
      infectious diseases.

PMID- 14976120
TI  - Health risks of overseas travel: perhaps treatment on return home should depend
      on having taken drug prophylaxis.

PMID- 14976121
TI  - Validity of Canadian studies: Author's response.

PMID- 14976125
TI  - Fibroblast network in rabbit sinoatrial node: structural and functional
      identification of homogeneous and heterogeneous cell coupling.
AB  - Cardiomyocytes form a conducting network that is assumed to be electrically
      isolated from nonmyocytes in vivo. In cell culture, however, cardiac fibroblasts
      can contribute to the spread of excitation via functional gap junctions with
      cardiomyocytes. To assess the ability of fibroblasts to form gap junctions in
      vivo, we combine in situ detection of connexins in rabbit sinoatrial node (a
      tissue that is particularly rich in fibroblasts) with identification of myocytes
      and fibroblasts using immunohistochemical labeling and confocal microscopy. We
      distinguish two spatially distinct fibroblast populations expressing different
      connexins: fibroblasts surrounded by other fibroblasts preferentially express
      connexin40, whereas fibroblasts that are intermingled with myocytes largely
      express connexin45. Functionality of homogeneous and heterogeneous cell coupling
      was investigated by dye transfer in sinoatrial node tissue explants. These
      studies reveal spread of Lucifer yellow, predominantly along extended threads of
      interconnected fibroblasts (probably via connexin40), and occasionally between
      neighboring fibroblasts and myocytes (probably via connexin45). Our findings show
      that cardiac fibroblasts form a coupled network of cells, which may be
      functionally linked to myocytes in rabbit SAN.

PMID- 14976124
TI  - Cyclosporin A enhances colchicine-induced apoptosis in rat cerebellar granule
      neurons.
AB  - 1. Cyclosporin A (CsA, 1-50 microM), an immunosuppressive drug with known
      neurotoxic effects, did not decrease the viability of primary cultures of rat
      cerebellar granule neurons (CGN) or induce apoptotic features. However, CsA
      specifically enhanced the cytotoxicity and apoptosis induced by colchicine (1
      microM). 2. Flavopiridol, an inhibitor of cyclin-dependent kinases (CDKs),
      prevented the neurotoxic effects of colchicine plus CsA. At 0.1-5 microM, it also
      showed antiapoptotic effects, as revealed by propidium iodide staining, flow
      cytometry and counting of cell nuclei. 3. Roscovitine (25-50 microM), a selective
      cdk1, 2 and 5 inhibitor, showed an antiapoptotic effect against colchicine- and
      colchicine plus CsA-induced apoptosis. 4. CsA increased the expression of cdk5
      and cdk5/p25 mediated by colchicine, a CDK involved in neuronal apoptosis. After
      treatment of CGN with colchicine plus CsA, the changes in the p25/p35 ratio
      pointed to cdk5 activation. 5. Immunohistochemical results showed a nuclear
      localization of cdk5 after neurotoxic treatment, which was prevented by cdk
      inhibitors. Thus, we propose a new mechanism of modulation of CsA neurotoxicity
      mediated by cdk5.

PMID- 14976127
TI  - Low CYP1A2 activity associated with testicular cancer.
AB  - The incidence rate of testicular cancer has increased during the last 50 years.
      An interplay between changing environmental factors and individual
      susceptibility, e.g. in foreign compound metabolizing enzymes, may have important
      influences on the risk of testicular cancer. The cytochrome P4501A2 (CYP1A2)
      enzyme and the bimodally expressed enzyme N-acetyltransferase2 (NAT2) metabolize
      many procarcinogens/carcinogens. The aim of this population-based case-control
      study was to investigate if CYP1A2 or NAT2 activity measured as a ratio of
      urinary metabolites of dietary caffeine is a risk factor in testicular cancer.
      378 men participated (80 seminomas, 104 non-seminomas and 194 controls). The
      CYP1A2 activity was lower in the cases than in the controls [median and 30-70%
      percentiles: 4.7 (3.9-5.7) and 5.2 (4.4-6.4), respectively]. The subjects were
      classified in tertiles with low, medium or high CYP1A2 activity. A low CYP1A2
      activity was associated with the highest risk of testicular cancer. Including all
      participants except men using drugs suspected to influence CYP1A2 activity (n =
      15), medium and low activity conferred odds ratios (ORs) of 1.54 [confidence
      intervals of 95% (CI(95%)) 0.93-2.55] and 2.11; CI(95%) (1.23-3.62),
      respectively, of having testicular cancer. Excluding smokers (n = 157) the ORs of
      medium and low activity were 3.63; CI(95%) (1.53-8.60) and 4.70; CI(95%) (2.03
      10.89), respectively. After further exclusion of cases that had received
      chemotherapy or radiation (n = 47), similar significant results were achieved. In
      the groups with the lowest CYP1A2 activity the ORs for seminoma and non-seminoma
      were 2.12; CI(95%) (0.93-4.81) and 2.10; CI(95%) (1.02-4.32). The phenotype of
      NAT2 was not associated with testicular cancer. In conclusion, we found no
      association of NAT2 phenotype to testicular cancer, whereas significant
      associations between CYP1A2 activity and testicular cancer were shown.

PMID- 14976126
TI  - Opioid-induced cardioprotection occurs via glycogen synthase kinase beta
      inhibition during reperfusion in intact rat hearts.
AB  - Glycogen synthase kinase (GSK) inhibition produced by ischemic preconditioning
      has been previously shown to be regulated through phosphatidylinositol-3 kinase
      (PI3K). Therefore, we determined whether opioid-induced cardioprotection (OIC)
      occurs during reperfusion by altering GSK phosphorylation through PI3K and target
      of rapamycin (TOR). Furthermore, we determined if selective GSK inhibitors,
      SB216763(SB21) or SB415286(SB41), emulate OIC. Rats were treated with the
      nonselective opioid agonist, morphine (MOR, 0.3 mg/kg), the delta-selective
      opioid agonist BW373U86 (BW, 1 mg/kg), or the GSK inhibitors, SB21 (0.6 mg/kg) or
      SB41(1.0 mg/kg), either 10 minutes before ischemia or 5 minutes before
      reperfusion. Five minutes before opioid or SB21 treatment, some rats received
      either the PI3K inhibitor wortmannin (15 microg/kg) or LY294002 (0.3 mg/kg) or
      the TOR inhibitor rapamycin (3 microg/kg). After 30 minutes of ischemia followed
      by 2 hours of reperfusion, infarct size was assessed. MOR, BW, SB41, and SB21
      reduced infarct size compared with vehicle when administered before ischemia
      (42.9+/-2.6, 40.3+/-2.3, 46.6+/-1.6, 42.2+/-1.8 versus 60.0+/-1.1%, respectively;
      P<0.001) and showed similar protection when administered 5 minutes before
      reperfusion (43.6+/-2.3, 40.2+/-2.6, 44.8+/-2.8, 39.4+/-0.8%, respectively;
      P<0.001). Wortmannin, LY294002, and rapamycin were found to inhibit OIC; however,
      they did not abrogate SB21-induced infarct size reduction. At 5 minutes of
      reperfusion, both MOR and BW increased P-GSKbeta at Ser9 in the ischemic zone
      compared with vehicle (181+/-20, 178+/-15 versus 75+/-17 DU, respectively;
      P<0.05), and this effect was abrogated by prior administration of wortmannin or
      rapamycin in MOR-treated rats. Furthermore, no differences were seen in
      phosphorylation of GSKalpha (Ser21 or Tyr279) or phosphorylation of GSKbeta
      (Tyr216). These data indicate that OIC occurs via the phosphorylation of GSKbeta
      at Ser9 during reperfusion.

PMID- 14976128
TI  - 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) triggers apoptosis by DNA
      double-strand breaks caused by inhibition of topoisomerase I.
AB  - 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) is one of the dietary
      carcinogens. At the initial step in the carcinogenic process, its exocyclic amino
      group is metabolically activated to the hydroxyamino derivative by the cytochrome
      P450 (CYP) 1A and 1B subfamily and then form DNA adducts, which are considered to
      be the main cause of DNA damage during the carcinogenic process. On the other
      hand, our previous study has shown that Trp-P-1 exhibits cytotoxicity to primary
      cultured rat hepatocytes, via induction of caspase-9-dependent apoptosis without
      being metabolized by CYP 1A1. In the present study, we investigated what type of
      DNA damage would be involved in the induction of apoptosis induced by Trp-P-1.
      When RL-34 cells derived from normal rat liver were treated with a high (30
      microM) concentration of Trp-P-1, apoptotic events such as the loss of cell
      viability, nuclear condensation and the activation of caspase-3 were observed. In
      these apoptotic cells, intracellular topoisomerase I activity was inhibited and
      histone H2AX phosphorylation, which occurs after introduction of DNA double
      strand breaks (DSBs), was observed in the early phase of the apoptosis. On the
      other hand, treatment with a non-apoptotic concentration (1 microM) of Trp-P-1
      increased the formation of 8-hydroxy-2'-deoxyguanosine. The formation of DNA
      adducts was detected at almost the same level in both cells exposed to the
      apoptotic and non-apoptotic concentrations of Trp-P-1. These results indicate
      that Trp-P-1-induced apoptosis was triggered by DNA DSBs through the inhibition
      of topoisomerase I but not the formation of DNA adducts.

PMID- 14976129
TI  - Temporal- and dose-dependent hepatic gene expression changes in immature
      ovariectomized mice following exposure to ethynyl estradiol.
AB  - Temporal- and dose-dependent changes in hepatic gene expression were examined in
      immature ovariectomized C57BL/6 mice gavaged with ethynyl estradiol (EE), an
      orally active estrogen. For temporal analysis, mice were gavaged every 24 h for 3
      days with 100 microg/kg EE or vehicle and liver samples were collected at 2, 4,
      8, 12, 24 and 72 h. Gene expression was monitored using custom cDNA microarrays
      containing 3067 genes/ESTs of which 393 exhibited a change at one or more time
      points. Functional gene annotation extracted from public databases associated
      temporal gene expression changes with growth and proliferation, cytoskeletal and
      extracellular matrix responses, microtubule-based processes, oxidative metabolism
      and stress, and lipid metabolism and transport. In the dose-response study,
      hepatic samples were collected 24 h following treatment with 0, 0.1, 1, 10, 100
      or 250 microg/kg EE. Thirty-nine of the 79 genes identified as differentially
      regulated at 24 h in the time course study exhibited a dose-response relationship
      with an average ED50 value of 47 +/- 3.5 microg/kg. Comparative analysis
      indicated that many of the identified temporal and dose-dependent hepatic
      responses are similar to EE-induced uterine responses reported in the literature
      and in a companion study using the same animals. Results from these studies
      confirm that the liver is a highly estrogen responsive tissue that exhibits a
      number of common responses shared with the uterus as well as distinct estrogen
      mediated profiles. These data will further aid in the elucidation of the
      mechanisms of action of estrogens in the liver as well as in other classical and
      non-classical estrogen responsive tissues.

PMID- 14976130
TI  - Conjugated linoleic acids (CLAs) decrease prostate cancer cell proliferation:
      different molecular mechanisms for cis-9, trans-11 and trans-10, cis-12 isomers.
AB  - The aims of this study were to examine the anti-proliferative effects of
      different concentrations of a commercial preparation of conjugated linoleic acids
      (CLA) mixture of isomers [cis-9, trans-11 CLA (c9,t11 CLA): trans-10, cis-12 CLA
      (50:50)] and their constituent isomers on PC-3, a human prostatic carcinoma cell
      line, and to study their effects on gene expression (mRNA and protein levels) of
      different enzymes and oncoproteins involved in oncogenesis and progression of
      prostate cancer. This includes pathways for arachidonic acid metabolism
      [cyclooxygenase 1 (COX-1), 2 (COX-2) and 5-lipoxygenase (5-LOX)], apoptosis (bcl
      2) and cell cycle control (p21(WAF/Cip1)). Our results indicate a significant
      decrease in PC-3 proliferation elicited by CLA, although with high variability
      between isomers. The trans-10, cis-12 CLA was the most effective isomer (55%
      inhibition). This isomer was also able to decrease bcl-2 gene expression and to
      increase p21(WAF1/Cip1) mRNA levels (60% increase at highest concentration). In
      contrast, cis-9, trans-11 had no effect on these proteins but had a clear effect
      on 5-LOX expression and to a lesser degree on COX-2 protein level isomers. In
      conclusion, the anti-proliferative effects on PC-3 of CLA mixture and their
      constituent isomers are not equivalent, due to the different pathways involved
      for individual isomers. Trans-10, cis-12 seems to work preferentially through
      modulation of apoptosis and cell cycle control, while c9,t11 CLA isomer affects
      arachidonic acid metabolism.

PMID- 14976131
TI  - APC mutations in sporadic colorectal carcinomas from The Netherlands Cohort
      Study.
AB  - The adenomatous polyposis coli (APC) gene is considered to be a gatekeeper in
      colorectal tumourigenesis. Inactivating mutations in APC have been reported in 34
      70% of sporadic colorectal cancer patients, the majority of which occur in the
      mutation cluster region (MCR). In this study, tumour tissue from 665 incident
      colorectal cancer patients, who originate from 120 852 men and women (55-69 years
      of age at baseline) participating in The Netherlands Cohort Study, was evaluated
      for the occurrence and type of APC mutations with regard to age at diagnosis,
      gender, family history of colorectal cancer, Dukes' stage, tumour differentiation
      and sub-localization. Mutation analysis of the MCR, which spans codons 1286-1513,
      was performed on archival adenocarcinoma samples using macrodissection, nested
      PCR and direct sequencing of purified PCR fragments. A large number of genetic
      aberrations (n = 978), including point mutations (n = 833), deletions (n = 126)
      and insertions (n = 19) was detected in the MCR in 72% of patients (479/665). In
      particular, we observed a large number of missense mutations, more than reported
      previously. This may indicate involvement in colorectal carcinogenesis, although
      their significance for APC functions is unclear. Truncating mutations were found
      in 37% of patients (248/665). Patients with rectosigmoid and rectum tumours
      relatively more frequently harboured C > T nonsense mutations and truncating
      frameshift mutations as compared with patients with proximal and distal colon
      tumours (P = 0.009 and P = 0.045, respectively). Differences in occurrence of
      truncating mutations with regard to tumour sub-localization suggest a different
      aetiology of tumourigenesis in colon and rectum.

PMID- 14976132
TI  - DNA array analysis of the effects of aspirin on colon cancer cells: involvement
      of Rac1.
AB  - Aspirin and other non-steroidal anti-inflammatory drugs show efficacy in the
      prevention of colon cancer. The mechanism by which they do this is unclear. We
      used a commercially available DNA microarray to study changes in gene expression
      in 1176 cancer related genes in the HT29 colon cancer cell line induced by
      aspirin. Overall we find more genes that are significantly induced than are
      repressed. The pattern of gene expression changes is different at high
      concentrations of aspirin (5 mM) than at lower levels (500 and 50 microM). Genes
      involved in DNA damage signaling, nucleotide metabolism and the stress response
      are induced, and cell cycle related genes repressed. The small GTPase Rac1 is
      highly induced and this was confirmed by immunoblotting. We show using
      immunohistochemistry that Rac1 is expressed in mature colonocytes at the
      intercrypt table in human and mouse colon tissue. These results support the
      previous findings that aspirin has different actions at high concentrations than
      at low concentrations and further show the use of DNA array technology in the
      investigation of drug mechanisms of action. Furthermore, they point towards a
      role for Rac1 in the action of aspirin in colon cancer.

PMID- 14976133
TI  - Suppression of human pancreatic cancer cell proliferation by AGN194204, an RXR
      selective retinoid.
AB  - Retinoids may be useful agents for the treatment of pancreatic cancer. However,
      retinoic acid receptor (RAR)-selective retinoids produce unwanted side effects.
      In contrast, retinoid X receptor (RXR)-selective retinoids produce fewer side
      effects; however, it was not known whether RXR-selective retinoids could reduce
      pancreatic tumor cell proliferation. In the present study, the novel RXR
      selective retinoid, AGN194204, was compared with that of other retinoids for the
      ability to suppress pancreatic cancer cell proliferation. We treated various
      pancreatic cancer cell lines with receptor-selective ligands and cytotoxic agents
      and monitored the effects on cell proliferation, markers of apoptosis and cell
      cycle. Our results indicate that AGN194204, at concentrations >10 nM, inhibits
      proliferation of MIA PaCa-2 and BxPC-3 cells but not the proliferation of AsPC-1
      cells. Moreover, in BxPC-3 and MIA PaCa-2 cells, AGN194204 was 10-100 times more
      effective than RAR-selective retinoids. AGN194204-dependent suppression of MIA
      PaCa-2 cell proliferation is associated with reduced cyclin E and cyclin
      dependent kinase 6 (cdk6) level, but cyclin D1, cdk2 and cdk4 content is not
      altered. In addition, p27 level increases 2-fold. The RXR-selective antagonist,
      AGN195393, reverses the AGN194204-dependent growth inhibition and the decline in
      cyclin E and cdk6 levels. In contrast, these changes are not reversed by
      treatment with the RAR antagonist, AGN193109. AGN194204 did not appear to alter
      cell apoptosis as measured by change in cleavage of procaspase-3, -8 or -9. We
      also examined the effects AGN194204 co-treatment with cytotoxic agents. Treatment
      of MIA PaCa-2 cells with AGN194204 + cisplatin, gemcitabine, 5-fluorouracil,
      interferon (IFN)alpha or IFNgamma resulted in an additive but not synergistic
      reduction in MIA PaCa-2 cell number. These results indicate that AGN194204, an
      RXR-selective retinoid, is a more effective inhibitor of pancreatic cell
      proliferation than the RAR-selective retinoids, and further indicate that
      AGN194204 produces an additive reduction in cell number when given with other
      agents. Our results suggest that RXR-selective ligands, which are less toxic than
      RAR-selective ligands, may be suitable agents for the treatment of pancreatic
      cancer.

PMID- 14976134
TI  - Diallyl disulfide (DADS) increases histone acetylation and p21(waf1/cip1)
      expression in human colon tumor cell lines.
AB  - Diallyl disulfide (DADS) is a naturally occurring organosulfur compound, from
      garlic, which exerts pleiotropic biological effects. In rodents, DADS inhibits
      colon chemically induced carcinogenesis. DADS anti-promoting effect may partly
      result from its ability to inhibit tumoral cell proliferation in vivo and in
      vitro. As far as DADS may modulate the expression of a subset of genes, we
      investigated DADS effect on histone acetylation, in two human colon tumor cell
      lines. Our study demonstrates that in Caco-2 and HT-29 cells treated for 6 h, 200
      microM DADS increases histone H3 acetylation (x2 and x1.4, respectively). In Caco
      2 cells, we also observed histone H4 hyperacetylation, preferentially at the
      lysine residues 12 and 16. We explored the effects of DADS and one of its
      metabolites, allyl mercaptan (AM), on histone deacetylase (HDAC) activity: using
      nuclear extracts of Caco-2 cells, 200 microM DADS decreased HDAC activity by 29%
      and AM at the same concentration was more efficient (92% inhibition). We also
      observed that DADS induced an increase in p21(waf1/cip1) expression, at mRNA and
      protein levels, in both cell lines. This effect was associated with an
      accumulation of cells in the G2 phase of the cell cycle. Our results suggest that
      in Caco-2 and HT-29 cells, DADS could inhibit cell proliferation through the
      inhibition of HDAC activity, histone hyperacetylation and increase in
      p21(waf1/cip1) expression. The present study provides evidence for cellular and
      molecular responses triggered by DADS that could be linked to its effect on
      histone acetylation and play a role in its protective properties on colon
      carcinogenesis.

PMID- 14976135
TI  - Defective expression of Notch1 and Notch2 in connection to alterations of c-Myc
      and Ikaros in gamma-radiation-induced mouse thymic lymphomas.
AB  - Gamma-radiation-induced thymic lymphomas constitute a heterogeneous group of T
      cell lymphomas. Some tumour suppressor genes and oncogenes have been shown to be
      defective in a fraction of such lymphomas, yet a considerable number of these
      remain elusive in terms of gene alterations. In the present work we present
      evidence that gamma-radiation-induced thymic lymphomas in (C57BL/6 J x BALB/c) F1
      hybrid mice often exhibit increased levels of Notch1 expression, but, contrary to
      what was expected, they also exhibit a clearly reduced Notch2 mRNA expression,
      suggesting a cooperative antagonism of these genes. These results represent the
      first reported instance for the involvement of Notch2 inactivation in the
      development of thymic primary tumours while confirming the role of Notch1 as an
      activated oncogene. Additional analyses revealed that c-Myc over-expression and
      partial inactivation of Znfn1a1/Ikaros appear to be relevant events some how
      coupled to alterations in Notch genes inducing these kinds of tumours.

PMID- 14976136
TI  - Apoptosis of vascular cells by oxidized LDL: involvement of caspases and LOX-1
      and its implication in atherosclerotic plaque rupture.

PMID- 14976137
TI  - Tied down by shear force: role for Tie1 in postnatal vascular remodeling?

PMID- 14976138
TI  - Development gone awry: congenital heart disease.
AB  - Significant advances in the understanding of the molecular and genetic basis of
      congenital heart disease have emerged from gene inactivation studies in mice and
      from human genetic investigations. However, the ability to utilize information
      gleaned from animal models to inform clinical care of patients depends on an
      accurate anatomic analysis and presentation in terms that are meaningful to the
      clinical pediatric cardiologist. Likewise, the enormous depth and breadth of
      accumulated clinical experience can inform the developmental biologist and can
      highlight the importance and interrelationships of particular phenotypes. The
      explosion of potentially informative genetic tools demands that basic scientists
      and clinicians concerned with congenital cardiac disease enhance the ongoing
      bidirectional dialogue. In some cases, categories of congenital disease familiar
      to clinicians are not recognized by developmental biologists, and mechanisms
      accepted by the biologist seem inconsistent with clinical experience. In this
      review, we summarize some of the more clinically significant forms of congenital
      heart disease, and we highlight relevant genetic and developmental pathways.

PMID- 14976139
TI  - The giant protein titin: a major player in myocardial mechanics, signaling, and
      disease.
AB  - The sarcomere contains, in addition to thin and thick filaments, a filament
      composed of the giant protein titin (also known as connectin). Titin molecules
      anchor in the Z-disc and extend to the M-line region of the sarcomere. The
      majority of titin's I-band region functions as a molecular spring. This spring
      maintains the precise structural arrangement of thick and thin filaments, and
      gives rise to passive muscle stiffness; an important determinant of diastolic
      filling. Earlier work on titin has been reviewed before. In this study, our main
      focus is on recent findings vis-a-vis titin's molecular spring segments in
      cardiac titins, including the discovery of fetal cardiac isoforms with novel
      spring elements. We also discuss new insights regarding the role of titin as a
      biomechanical sensor and signaling molecule. We will end with focusing on the
      rapidly growing knowledge regarding titinopathies.

PMID- 14976140
TI  - At the crossroads of myocardial signaling: the role of Z-discs in intracellular
      signaling and cardiac function.
AB  - Understanding the molecular interactions among components of cardiac Z-discs and
      their role in signaling has become pivotal in explaining long- and short-term
      regulation of cardiac function. In striated muscle, the ends of the thin
      filaments from opposing sarcomeres overlap and are cross-linked by an elaborate
      array of proteins to form a highly ordered, yet dynamic network that is the Z
      disc. We review here a current picture of the function and structure of the Z
      disc of mammalian cardiac myocytes. We emphasize provocative findings that
      advance new theories about the place of cardiac Z-discs in myocardial intra- and
      intercellular signaling in myocardial physiology and pathology. Relatively new
      approaches, especially yeast two-hybrid screens, immunoprecipitation, and pull
      down assays, as well as immunohistochemical analysis have significantly altered
      previous views of the protein content of the Z-disc. These studies have generally
      defined domain structure and binding partners for Z-disc proteins, but the
      functional significance of the binding network and of the domains in cardiac cell
      biology remains an unfolding story. Yet, even at the present level of
      understanding, perceptions of potential functions of the Z-disc proteins are
      expanding greatly and leading to new and exciting experimental approaches toward
      mechanistic understanding. The theme of the following discussion of these Z-disc
      proteins centers on their potential to function not only as a physical anchor for
      myofilament and cytoskeletal proteins, but also as a pivot for reception,
      transduction, and transmission of mechanical and biochemical signals.

PMID- 14976141
TI  - Differential response to exogenous and endogenous myostatin in myoblasts suggests
      that myostatin acts as an autocrine factor in vivo.
AB  - Myostatin is a member of the TGF-beta superfamily that is essential for proper
      regulation of skeletal muscle growth. As do other TGF-beta superfamily members,
      myostatin signals into the cell via a receptor complex that consists of two
      distinct transmembrane proteins, known as the type I and type II receptors.
      Vertebrates have seven distinct type I receptors, each of which can mix and match
      with one of five type I receptors to mediate signals for all the TGF-beta family
      ligands. Accumulating evidence indicates that myostatin shares its pair of
      receptors with activin, and therefore, the question arises about how specificity
      in signaling is achieved. Our hypothesis is that a mechanism has to exist to
      restrict myostatin actions to the muscle cells. To investigate this possibility,
      we compared the effect of endogenous myostatin (myostatin overexpressed by
      myoblasts) and exogenous myostatin (recombinant myostatin added to the culture
      medium) in cultured myoblasts. As opposed to exogenous myostatin, endogenous
      myostatin induced the transcription of a reporter vector in cultured myoblasts.
      Notably, the myostatin concentrations that failed to induce a response in
      myoblasts were effective in MCF-7 cells (human mammary carcinoma) and in HepG2
      cells (human hepatic carcinoma). Based on our observations, we propose that a
      mechanism exists that differentially regulates the bioavailability of endogenous
      and exogenous myostatin to muscle cells. This is consistent with a model in which
      myostatin actions are exerted in vivo in an autocrine fashion.

PMID- 14976142
TI  - Photic stimulation inhibits growth hormone secretion in rats: a hypothalamic
      mechanism for transient entrainment.
AB  - It is well established that photic cues are used by the suprachiasmatic nucleus
      (SCN) to entrain circadian rhythms to the light/dark cycle, but the role of
      photic stimuli in the regulation of ultradian neuroendocrine rhythms is ill
      defined. In relation to the rhythms of GH secretion, recent studies have shown
      that nocturnal photic stimulation induces gene expression not only in the SCN but
      also in periventricular (PeN) somatostatin (SRIF) neurons. We have, therefore,
      investigated the effect of nocturnal photic stimulation on spontaneous and
      induced GH secretion in conscious rats. Nocturnal photic stimulation (lights on
      at 2400 h for 1 h) suppressed spontaneous GH secretion in male and female rats
      and reduced the GH response to SRIF withdrawal and iv injection of GH-releasing
      factor. A similar trough in GH secretion was also observed during the first hour
      of the normal light phase (0600 h). Using immunohistochemical analysis, we have
      also shown that expression of the transcription factor, Egr-1, is induced at the
      commencement of the light phase in the SCN, PeN, and medial preoptic nucleus.
      This effect is abolished by maintaining rats in the dark during this period.
      These data, together with our previous demonstration that 50% of SRIF-positive
      neurons in the PeN coexpress Egr-1 after photic stimulation, suggest that
      activation of SRIF neurons in the PeN may entrain the episodes of GH secretion to
      the dark/light interface. However, the absence of synchrony in GH pulses between
      animals by the second half of the light period suggests that this entrainment is
      transient.

PMID- 14976143
TI  - Histone deacetylase inhibitors restore radioiodide uptake and retention in poorly
      differentiated and anaplastic thyroid cancer cells by expression of the
      sodium/iodide symporter thyroperoxidase and thyroglobulin.
AB  - Iodide uptake by the thyroid is mediated by the sodium/iodide symporter. Upon
      iodide uptake, thyroperoxidase catalyzes iodination of tyrosine residues in
      thyroglobulin, retaining iodide within thyroid follicles. Dedifferentiation
      induced loss of these functions in cancers, rendering them unresponsive to
      radioiodide, occurs with most poorly differentiated and anaplastic tumors. We
      focused on the histone deacetylase (HDAC) inhibitors (HDACI) as a way to induce
      differentiation of thyroid cancer cells. We assessed re-expression of thyroid
      specific genes mRNA induced by HDACI using quantitative RT-PCR and immunostaining
      in poorly differentiated papillary and anaplastic thyroid cancer cells. HDACI
      induced expression of thyroid-specific gene mRNAs and proteins, and accumulation
      of radioiodide through iodination of generic cellular proteins were detected.
      HDACI-treated tumors could specifically accumulate (125)I as revealed by imaging
      experiments and radioiodide concentration in vivo. In an attempt to determine the
      mechanism by which these gene expressions occurred, we detected the inhibition of
      protein synthesis by cycloheximide, which up-regulated the expression of
      thyroperoxidase and thyroglobulin mRNA in HDACI-treated cells and down-regulated
      that of sodium/iodide symporter mRNA. Together, our results suggest that HDACI
      induced expression of thyroid-specific genes, some of which is mediated by some
      protein synthesis, may contribute to development of novel strategy against
      thyroid cancer.

PMID- 14976144
TI  - Glucose-induced expression of the cyclin-dependent protein kinase 5 activator p35
      involved in Alzheimer's disease regulates insulin gene transcription in
      pancreatic beta-cells.
AB  - The deposition of amyloid within the insulin-producing islets of Langerhans in
      the pancreas is a common pathological finding in patients with type 2 diabetes.
      Its relationship with age and the progression of the disease resembles the
      pathological deposition of beta-amyloid in the brains of Alzheimer's patients.
      Endocrine cells of pancreatic islets and cells of neuronal lineages express a
      shared subset of specialized genes. The hyperactivity of the cyclin-dependent
      protein kinase CDK5, involved in the development and differentiation of the
      nervous system, is associated with Alzheimer's disease. Overactivity of CDK5
      occurs by proteolytic cleavage and cellular mislocalization of its activator,
      p35. These alterations in p35/CDK5 signaling pathway may mediate, at least in
      part, the functional abnormalities characteristic of Alzheimer's disease. In this
      study we report that both the p35 and CDK5 genes are expressed in insulin
      producing beta-cells of the pancreas. We detect in beta-cells the formation of an
      active p35/CDK5 complex with specific kinase activity. Notably, elevations of the
      extracellular concentration of glucose result in increases in p35 mRNA and
      protein levels that parallel elevations of p35/CDK5 activity. Functional studies
      show that p35 stimulates the activity of the insulin promoter and that the
      stimulation requires CDK5 because stimulation is blocked by roscovitine, an
      inhibitor of CDK5 activity, a dominant negative form of CDK5, and small
      interfering RNAs against p35. Our findings indicate that the expression of p35
      and CDK5 in insulin-producing beta-cells ensembles a new signaling pathway, the
      activity of which is controlled by glucose, and its functional role may comprise
      the regulation of various biological processes in beta-cells, such as is the case
      for expression of the insulin gene.

PMID- 14976145
TI  - Fibroblast growth factor 19 increases metabolic rate and reverses dietary and
      leptin-deficient diabetes.
AB  - Hormonal control of metabolic rate can be important in regulating the imbalance
      between energy intake and expenditure that underlies the development of obesity.
      In mice fed a high-fat diet, human fibroblast growth factor 19 (FGF19) increased
      metabolic rate [1.53 +/- 0.06 liters O(2)/h.kg(0.75) (vehicle) vs. 1.93 +/- 0.05
      liters O(2)/h.kg(0.75) (FGF19); P < 0.001] and decreased respiratory quotient
      [0.82 +/- 0.01 (vehicle) vs. 0.80 +/- 0.01 (FGF19); P < 0.05]. In contrast to the
      vehicle-treated mice that gained weight (0.14 +/- 0.05 g/mouse.d), FGF19-treated
      mice lost weight (-0.13 +/- 0.03 g/mouse.d; P < 0.001) without a significant
      change in food intake. Furthermore, in addition to a reduction in weight gain,
      treatment with FGF19 prevented or reversed the diabetes that develops in mice
      made obese by genetic ablation of brown adipose tissue or genetic absence of
      leptin. To explore the mechanisms underlying the FGF19-mediated increase in
      metabolic rate, we profiled the FGF19-induced gene expression changes in the
      liver and brown fat. In brown adipose tissue, chronic exposure to FGF19 led to a
      gene expression profile that is consistent with activation of this tissue. We
      also found that FGF19 acutely increased liver expression of the leptin receptor
      (1.8-fold; P < 0.05) and decreased the expression of acetyl coenzyme A
      carboxylase 2 (0.6-fold; P < 0.05). The gene expression changes were consistent
      with the experimentally determined increase in fat oxidation and decrease in
      liver triglycerides. Thus, FGF19 is able to increase metabolic rate concurrently
      with an increase in fatty acid oxidation.

PMID- 14976146
TI  - Critical in vivo roles for classical estrogen receptors in rapid estrogen actions
      on intracellular signaling in mouse brain.
AB  - Estrogen exerts classical genomic as well as rapid nongenomic actions on neurons.
      The mechanisms involved in rapid estrogen signaling are poorly defined, and the
      roles of the classical estrogen receptors (ERs alpha and beta) are unclear. We
      examined here the in vivo role of classical ERs in rapid estrogen actions by
      evaluating the estrogen-induced effects on two major signaling pathways within
      the brains of alphaER-, betaER-, and double alphabetaER-knockout (ERKO)
      ovariectomized female mice. Estrogen significantly (P < 0.05) increased the
      numbers of phospho-cAMP response element binding protein (phospho-CREB)
      immunoreactive cells in specific brain regions of wild-type mice in a time
      dependent manner beginning within 15 min. In brain areas that express
      predominantly ERbeta, this response was absent in betaERKO mice, whereas brain
      regions that express mostly ERalpha displayed no change in alphaERKO mice. In the
      medial preoptic nucleus (MPN), an area that expresses both ERs, the estrogen
      induced phosphorylation of CREB was normal in both alphaERKO and betaERKO mice.
      However, estrogen had no effect on CREB phosphorylation in the MPN, or any other
      brain region, in double alphabetaERKO animals. Estrogen was also found to
      increase MAPK phosphorylation levels in a rapid (<15 min) manner within the MPN.
      In contrast to CREB signaling, this effect was lost in either alphaERKO or
      betaERKO mice. These data show that ERalpha and ERbeta play region- and pathway
      specific roles in rapid estrogen actions throughout the brain. They further
      indicate an indispensable role for classical ERs in rapid estrogen actions in
      vivo and highlight the importance of ERs in coordinating both classical and rapid
      actions of estrogen.

PMID- 14976147
TI  - The liver-enriched inhibitory protein isoform of CCAAT/enhancer-binding protein
      beta, but not nuclear factor-kappaB, mediates the transcriptional inhibition of
      beta-casein by tumor necrosis factor-alpha.
AB  - TNF-alpha is a physiological regulator of mammary gland development that
      stimulates the growth of both normal and malignant mammary epithelial cells in
      primary culture and inhibits functional differentiation. To understand how TNF
      exerts its effects, the current study examined the mechanism by which TNF down
      regulates expression of the beta-casein and whey acidic protein (WAP) genes. TNF
      treatment markedly decreased activity of the beta-casein and WAP promoters in
      transiently transfected HC11 mammary epithelial cells. Overexpression of the
      nuclear factor-kappaB (NFkappaB) p50 and/or p65 proteins increased the
      transcriptional activity of the beta-casein and WAP promoters in HC11 cells,
      suggesting that the inhibitory effect of TNF on transcription of these genes is
      not mediated by NFkappaB. This was further confirmed in experiments in which an
      NFkappaB super-repressor was overexpressed, and by deletion of an NFkappaB
      binding site in the beta-casein promoter. In contrast, we found that TNF induced
      both nuclear expression and the DNA-binding activity of liver-enriched inhibitory
      protein (LIP) isoform of CCAAT/enhancer-binding protein beta. Moreover,
      cotransfection of LIP and beta-casein expression vectors showed that LIP
      suppressed the transcriptional activity of the beta-casein promoter. Together,
      these results suggest that LIP plays a critical role in mediating TNF-induced
      down-regulation of the beta-casein gene.

PMID- 14976148
TI  - Transactivation of the insulin-like growth factor-I receptor by angiotensin II
      mediates downstream signaling from the angiotensin II type 1 receptor to
      phosphatidylinositol 3-kinase.
AB  - Angiotensin II (AngII) activates phosphatidylinositol 3-kinase (PI3-kinase), a
      known effector of receptor tyrosine kinases. Treatment of smooth muscle cells
      with AngII has also been shown to promote phosphorylation of various tyrosine
      kinase receptors. We therefore investigated the relationship between AngII and
      IGF-I receptor activation in smooth muscle cells with a phosphorylation-specific
      antibody. Our experiments showed that IGF-I receptor phosphorylation was
      maximally stimulated within 10 min by AngII. Inclusion of an IGF-I-neutralizing
      antibody in the culture media did not prevent IGF-I receptor phosphorylation
      after AngII treatment, which argues that a paracrine/autocrine loop is not
      required. Furthermore, this process was blocked by losartan and 1-(1,1
      dimethylethyl)-1-(4-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (PP-1),
      indicating stimulation of IGF-I receptor phosphorylation occurs via AngII type 1
      receptor-dependent activation of Src kinase. The functional significance of IGF-I
      receptor transactivation was examined with selective inhibitors of the IGF-I
      receptor kinase (AG1024, AG538). When AngII-treated cells were incubated with
      AG1024 or AG538, phosphorylation of the regulatory p85 subunit of PI3-kinase was
      blocked. Furthermore, phosphorylation of the downstream factor p70(S6K) did not
      occur. In contrast, AG1024 did not prevent MAPK or Src kinase activation by
      AngII. AG1024 also did not inhibit AngII-dependent cell migration, although this
      process was blocked by inhibitors of the epidermal growth factor and platelet
      derived growth factor receptors. Transactivation of the IGF-I receptor is
      therefore a critical mediator of PI3-kinase activation by AngII but is not
      required for stimulation of the MAPK cascade.

PMID- 14976149
TI  - Plasma fluorescence scanning and fecal porphyrin analysis for the diagnosis of
      variegate porphyria: precise determination of sensitivity and specificity with
      detection of protoporphyrinogen oxidase mutations as a reference standard.
AB  - BACKGROUND: Variegate porphyria (VP) is the autosomal dominant disorder
      associated with deficiency of the enzyme protoporphyrinogen oxidase (PPOX).
      Plasma fluorescence scanning has been reported to be a more sensitive test for VP
      than traditional fecal chromatography. Previous comparisons of these techniques
      predated identification of the PPOX gene. We assessed these techniques in a large
      group of patients characterized for VP at the DNA level. METHODS: We evaluated
      all patients for whom the genotype and a plasma scan or fecal porphyrin result
      were available. Mutations were detected by restriction digest analysis. Plasma
      fluorescence scanning was conducted according to published methods. Fecal
      porphyrins were identified and quantified by thin-layer chromatography. RESULTS:
      Plasma fluorescence scanning was assessed in 679 patients (205 with VP who were
      carriers of a PPOX mutation, either with disease symptoms or asymptomatic) and
      fecal analysis in 473 (190 with VP). Sensitivity and specificity of both tests
      were higher in adults than in children and higher for adults with disease
      symptoms than for asymptomatic carriers. In a direct comparison in 168 adults (73
      with VP), plasma scanning was significantly more sensitive than fecal porphyrin
      analysis [sensitivity, 0.96 (95% confidence interval, 0.89-0.99) vs 0.77 (0.66
      0.85)]. Fecal coproporphyrin [area under the curve, 0.87 (0.83-0.90)] was a
      better predictor of VP than protoporphyrin [0.80 (0.76-0.84)]. CONCLUSIONS:
      Plasma scanning is a more sensitive and specific test for VP than fecal porphyrin
      analysis. Neither test is sensitive in children, and both are less sensitive in
      asymptomatic carriers than in symptomatic cases. DNA analysis therefore remains
      the preferred method for the identification of carriers, particularly in
      children.

PMID- 14976150
TI  - A new paradigm in the treatment of carcinoma: specific molecular targeting.

PMID- 14976151
TI  - Dehydroepiandrosterone (DHEA): a misunderstood adrenal hormone and spine-tingling
      neurosteroid?

PMID- 14976152
TI  - Can you teach an old dogma new tricks?

PMID- 14976153
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 14976154
TI  - National Hormone Peptide Program. National Institute of Diabetes and Digestive
      and Kidney Diseases. Peptides hormone, antisera & other regents available.

PMID- 14976155
TI  - Parkin genetics: one model for Parkinson's disease.
AB  - The genetic epidemiology of late-onset idiopathic Parkinson's disease (PD) and
      'parkin-proven' parkinsonism (AR-JP) are limited. The clinical phenotype,
      prognosis and treatments are similar although PD is prevalent while AR-JP is
      rare. Molecular genetic and functional analysis suggests the E3 ubiquitin protein
      ligase activity of parkin, and the ubiquitin-proteosomal pathway, is central to
      disease pathogenesis. Herein, we compare and contrast PD and AR-JP and discuss
      the implications of recent data about parkin's genomic organization, regulation
      and function.

PMID- 14976156
TI  - Inflammatory bowel disease susceptibility loci defined by genome scan meta
      analysis of 1952 affected relative pairs.
AB  - Crohn's disease and ulcerative colitis (the inflammatory bowel diseases) have a
      strong genetic component. Although over 20 putative susceptibility loci have been
      identified by individual genome scans, the majority of these loci have not been
      replicated. Many individual studies are at the lower limit of acceptable power
      for complex disease linkage analysis. Genome scan meta-analysis (GSMA), by use of
      sample sizes an order of magnitude greater than individual linkage studies, has
      increased power to detect novel loci, may confirm or refute regions detected in
      smaller individual studies, and enables regions to be prioritized for further
      gene identification efforts. Genome scan data (markers, significance scores) were
      obtained from 10 separate studies and meta-analysis was performed using the GSMA
      method. These studies comprised 1952 inflammatory bowel disease, 1068 Crohn's
      disease and 457 ulcerative colitis affected relative pairs. Study results were
      divided into 34 cM chromosomal bins, ranked, weighted by study size, summed
      across studies and bin-by-bin significance obtained by simulation. A region on
      chromosome 6p (containing the HLA) met genome wide significance for inflammatory
      bowel disease. Loci meeting suggestive significance for inflammatory bowel
      disease were 2q, 3q, 5q, 7q and 16 (NOD2/CARD15 region); Crohn's disease, 2q, 3q,
      6p, 16 (NOD2/CARD15 region), 17q, 19p; and ulcerative colitis, 2q. Clustering of
      adjacent bins was observed for chromosomes 6p, 16, 19p. The meta-analysis has
      identified novel loci and prioritized genomic regions for further gene
      identification studies.

PMID- 14976157
TI  - A candidate gene association study on preterm delivery: application of high
      throughput genotyping technology and advanced statistical methods.
AB  - Preterm delivery (PTD) is the leading cause of infant mortality and morbidity
      worldwide. The etiology of PTD is largely unknown but is believed to be complex,
      encompassing multiple genetic and environmental determinants. To date, reports of
      genetic studies on PTD are sparse. We conducted a large-scale case-control study
      exploring the associations of 426 single-nucleotide polymorphisms with PTD in 300
      mothers with PTD and 458 mothers with term deliveries at the Boston Medical
      Center. Twenty-five candidate genes were included in the final haplotype
      analysis, and a significant association of F5 gene haplotype with PTD was
      revealed and remained significant after Bonferroni correction for multiple
      testing (P=0.025). We applied different statistical algorithms (both Gibbs
      sampling and expectation-maximization) in reconstructing haplotype phases and
      different tests (both likelihood ratio test and permutation test) in association
      analyses, and all yielded similar results. We also performed exploratory
      ethnicity-specific analyses, which confirmed the consistent findings of the F5
      gene across the ethnic groups. Moreover, IL1R2 (P=0.002 in Blacks), NOS2A
      (P<0.001 in Whites) and OPRM1 (P=0.004 in Hispanics) gene haplotypes were
      associated with PTD in specific ethnic groups but not at global significance
      level. In summary, our results underscore the potentially important role of F5
      gene variants in the pathogenesis of PTD, and demonstrate the utility of high
      throughput genotyping and a haplotype-based approach in dissecting genetic basis
      of complex traits.

PMID- 14976158
TI  - The oligogenic properties of Bardet-Biedl syndrome.
AB  - Bardet-Biedl syndrome (BBS: OMIM 209900) is a rare developmental disorder that
      exhibits significant clinical and genetic heterogeneity. Although modeled
      initially as a purely recessive trait, recent data have unmasked an oligogenic
      mode of disease transmission, in which mutations at different BBS loci can
      interact genetically in some families to cause and/or modify the phenotype. Here,
      I will review and discuss recent advances in elucidating both genetic and
      cellular aspects of this phenotype and their potential application in
      understanding the genetic basis of phenotypic variability and oligogenic
      inheritance.

PMID- 14976159
TI  - The law of mass action applied to neurodegenerative disease: a hypothesis
      concerning the etiology and pathogenesis of complex diseases.
AB  - Loci underlying autosomal dominant forms of most neurodegenerative disease have
      been identified: prion mutations cause Gerstmann Straussler syndrome and
      hereditary Creuzfeldt-Jakob disease, tau mutations cause autosomal dominant
      frontal temporal dementia, and alpha-synuclein mutations cause autosomal dominant
      Parkinson's disease. In all these cases, the pathogenic mutation is in the
      protein that is deposited in the diseased tissue and in these cases the whole
      protein is deposited. In Alzheimer's disease, mutations in APP or presenilin 1 or
      2 cause autosomal dominant disease and these are the substrate and proteases,
      respectively, which are responsible for the production of the deposited peptide,
      Abeta. Thus, in all cases, the mutations lead to the disease by a mechanism that
      involves the deposition process. We briefly review this remarkably predictable
      biology, but also point out that it seems sporadic forms of all these diseases
      are predisposed to by genetic variability at the same loci, strongly suggesting
      that the quantity of the normal protein produced influences risk for the sporadic
      forms of the disease. The evidence for this assertion is strongest in Parkinson's
      disease (PD), where genetic variability in alpha-synuclein expression affects
      risk of developing disease, although the oldest evidence for the notion that
      increased expression of normal sequence protein can lead to disease comes from
      the observation of Alzheimer's disease in trisomy 21 cases. From these
      observations, we make predictions concerning the etiology and pathogenesis of
      neurodegenerative diseases in general.

PMID- 14976160
TI  - A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain
      perception.
AB  - Identification of genes associated with pain insensitivity syndromes can increase
      the understanding of the pathways involved in pain and contribute to the
      understanding of how sensory pathways relate to other neurological functions. In
      this report we describe the mapping and identification of the gene responsible
      for loss of deep pain perception in a large family from northern Sweden. The loss
      of pain perception in this family is characterized by impairment in the sensing
      of deep pain and temperature but with normal mental abilities and with most other
      neurological responses intact. A severe reduction of unmyelinated nerve fibers
      and a moderate loss of thin myelinated nerve fibers are observed in the patients.
      Thus the cases in this study fall into the class of patients with loss of pain
      perception with underlying peripheral neuropathy. Clinically they best fit into
      HSAN V. Using a model of recessive inheritance we identified an 8.3 Mb region on
      chromosome 1p11.2-p13.2 shared by the affected individuals in the family.
      Analysis of functional candidate genes in the disease critical region revealed a
      mutation in the coding region of the nerve growth-factor beta (NGFB) gene
      specific for the disease haplotype. This NGF mutation seems to separate the
      effects of NGF involved in development of central nervous system functions such
      as mental abilities, from those involved in peripheral pain pathways. This
      mutation could therefore potentially provide an important tool to study different
      roles of NGF, and of pain control.

PMID- 14976161
TI  - Tissue-specific imprinting of the G protein Gsalpha is associated with tissue
      specific differences in histone methylation.
AB  - The G protein Gsalpha is imprinted in a tissue-specific manner, being primarily
      expressed from the maternal allele in some tissues, such as renal proximal
      tubules. The Gsalpha promoter is unmethylated, but is downstream of a
      differentially methylated region [the exon 1A differentially methylated region
      (DMR)] that is methylated on the maternal allele. Maternal Gsalpha null mutations
      or loss of maternal-specific exon 1A methylation leads to
      pseudohypoparathyroidism types 1A or 1B, respectively. We now have examined the
      chromatin state of each parental allele within the exon 1A-Gsalpha promoter
      region by chromatin immunoprecipitation of samples derived from mice with
      heterozygous deletions within the region using antibodies to covalently modified
      histones. The exon 1A DMR had allele-specific differences in histone acetylation
      and methylation, with histone acetylation and H3 lysine 4 (H3K4) methylation of
      the paternal allele, and H3 lysine 9 (H3K9) methylation of the maternal allele.
      Both parental alleles had similar levels of histone acetylation and H3K4
      methylation within the Gsalpha promoter and first exon, with no H3K9 methylation.
      In liver, where Gsalpha is biallelically expressed, both parental alleles had
      similar levels of tri- and dimethylated H3K4 within the Gsalpha first exon. In
      contrast, in renal proximal tubules there was a greater ratio of tri- to
      dimethylated H3K4 of Gsalpha exon 1 in the more transcriptionally active maternal
      as compared with the paternal allele. These results show that allele-specific
      differences in Gsalpha expression correlate in a tissue-specific manner with
      allele-specific differences in the extent of H3K4 methylation, and are the first
      demonstration that chronic transcriptional activation in mammals is correlated
      with trimethylation of H3K4.

PMID- 14976162
TI  - Genomic evidence for recent positive selection at the human MDR1 gene locus.
AB  - The MDR1 multidrug transporter regulates the traffic of drugs, peptides and
      xenobiotics into the body as well as sensitive tissues like the brain, germ cells
      and the developing fetus. Hence, it may influence an individual's response to
      drugs as well as his/her susceptibility to complex diseases in which
      environmental factors, especially xenobiotics, play a role. Polymorphisms within
      this gene, especially single-nucleotide polymorphism e26/3435(C/T), have been
      variously associated with differences in MDR1 expression, function, drug response
      and disease susceptibility. Here, we report the detailed characterization of the
      haplotype and linkage disequilibrium architecture of the entire 200 kb of the
      MDR1 gene in five world populations, namely, Chinese, Malays, Indians, Caucasians
      and African-Americans. We observed varied haplotype diversity across the entire
      gene in the different populations. The major haplotype mh5, which contains the
      subhaplotype e12/1236T-e21/2677T-e26/3435T, is highly represented among the four
      non-African populations, while mh7, which contains the subhaplotype e12/1236C
      e21/2677G-e26/3435C, accounts for over a third of African-American chromosomes.
      These observations are inconsistent with a simple population evolution model, but
      instead are suggestive of recent historical events that have maintained such long
      range linkage disequilibrium. Using a modified long-range haplotype test, we
      found statistically significant evidence of recent positive selection for the
      e21/2677T and e26/3435T alleles in the Chinese population, and for the e26/3435T
      allele in the Malay population. Interestingly, we also detected evidence for
      positive selection of the alternative allele e26/3435C in the African-American
      population. These data suggest that independent mutational events may have
      occurred on the mh5 and mh7 haplotypes of the MDR1 gene to confer positive
      selection in the non-African and African-American populations, respectively.

PMID- 14976163
TI  - A mouse genetic model for familial cholestasis caused by ATP8B1 mutations reveals
      perturbed bile salt homeostasis but no impairment in bile secretion.
AB  - Mutations in ATP8B1, a broadly expressed P-type ATPase, result, through unknown
      mechanisms, in disorders of bile secretion. These disorders vary in severity from
      mild and episodic to progressive with liver failure. We generated
      Atp8b1G308V/G308V mutant mice, which carry a mutation orthologous to that present
      in homozygous form in patients from the Amish index kindred for severe ATP8B1
      disease. In contrast to human patients, Atp8b1(G308V/G308V) mice had unimpaired
      bile secretion and no liver damage, but showed mild abnormalities including
      depressed weight at weaning and elevated serum bile salt levels. We challenged
      the hepatobiliary metabolism of Atp8b1G308V/G308V mice by administering exogenous
      bile salts. Upon bile salt feeding, Atp8b1G308V/G308V mice, but not wild-types,
      demonstrated serum bile salt accumulation, hepatic injury and expansion of the
      systemic bile salt pool. Unexpectedly, this failure of bile salt homeostasis
      occurred in the absence of any defect in hepatic bile secretion. Upon infusion of
      a hydrophobic bile salt, wild-type mice developed cholestasis while
      Atp8b1G308V/G308V mice maintained high biliary output and more extensively
      rehydroxylated the infused bile salt. Increased bile salt hydroxylation, which
      reduces bile salt toxicity, may explain the milder phenotype in Atp8b1G308V/G308V
      mice compared with humans with the equivalent mutation. These results demonstrate
      the key role of Atp8b1 in bile salt homeostasis and highlight the importance of
      bile salt hydroxylation in the prevention of cholestasis. The mouse phenotype
      reveals that loss of Atp8b1 disrupts bile salt homeostasis without impairment of
      canalicular bile secretion; in humans this process is likely to be obscured by
      early onset of severe liver disease.

PMID- 14976164
TI  - Oculopharyngeal muscular dystrophy-like nuclear inclusions are present in normal
      magnocellular neurosecretory neurons of the hypothalamus.
AB  - Intranuclear inclusions composed of tubular filaments constitute a pathological
      hallmark of oculopharyngeal muscular dystrophy (OPMD). Autosomal dominant OPMD is
      caused by (GCG) repeat expansions in the gene that encodes for poly(A) binding
      protein nuclear 1 (PABPN1). The mutation results in the expansion of a
      polyalanine stretch in the N-terminus of the protein. It has been proposed that
      mutated PABPN1 induces protein aggregation, which in turn causes the formation of
      the filamentous nuclear inclusions. Here we report the presence of intranuclear
      inclusions composed of tubular filaments in oxytocin-producing neurons from
      normal rat hypothalamus. Like OPMD inclusions, the filamentous structures in
      neurosecretory neurons accumulate PABPN1, poly(A) RNA, ubiquitin and proteasomes.
      These inclusions do not contain members of Hsp40 and HDJ-2/DNAJ families of
      chaperones. The proportion of oxytocin-producing neurons that contain inclusions
      decreases during parturition and lactation (when synthesis and release of
      oxytocin is maximal) and increases at 1 day post-weaning (when occurs a drastic
      reduction in the production of the hormone). Thus, PABPN1 filaments in normal
      neurons are dynamic structures, the appearance of which correlate with changes in
      cellular activity. These data provide the first physiological evidence that
      polyalanine expansions are not essential to induce polymerization of PABPN1 into
      filamentous nuclear inclusions.

PMID- 14976165
TI  - BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent
      on K6 of ubiquitin, in cells during DNA replication and repair.
AB  - The N-terminus of the BRCA1 protein bears a RING finger domain that functions as
      an E3 ubiquitin ligase in vitro where it is able to catalyse the synthesis of
      monoubiquitin and polyubiquitin targeted proteins. This activity is greatly
      increased when BRCA1 is in a complex with its N-terminal binding partner BARD1.
      In this report we use an immunohistochemical approach to demonstrate the
      association of cellular BRCA1 with the end product of the ubiquitin conjugation
      and ligation pathway, conjugated ubiquitin. Association is apparent at DNA
      replication structures in S-phase and following treatment with hydroxyurea and
      also at sites of double strand break repair after exposure to ionizing radiation.
      Down-regulation of endogenous, cellular BRCA1 : BARD1 using siRNA results in
      abrogation of ubiquitin conjugation in these structures, suggesting that
      heterodimer activity is required for their formation. Conversely, ectopically
      expressed full-length BRCA1, but not BRCA1 bearing specific N-terminal amino acid
      substitutions, is able to cooperate with BARD1 to increase ubiquitin conjugation
      in cells. Conjugation of ubiquitin in foci is inhibited by the expression of
      ubiquitin bearing a lysine 6 mutation suggesting that the ubiquitin polymers
      formed at these sites are dependent on lysine-6 for linkage. Together these data
      demonstrate that BRCA1 directed ligation of ubiquitin occurs during S-phase and
      in response to replication stress and DNA damage and is therefore likely to be a
      significant aspect of BRCA1 cellular activity.

PMID- 14976166
TI  - Health promotion's record card: how principled are we 20 years on?

PMID- 14976167
TI  - Exploring the intersectoral partnerships guiding Australia's dietary advice.
AB  - In 1986, the Ottawa Charter alerted a new generation of health promotion
      practitioners to the benefits of working with the non-health sectors, including
      the commercial sector. Since then, the establishment of partnerships with
      government and non-government bodies has been advanced as a positive way of
      fostering policies that enhance health and well-being. The food and nutrition
      field has enthusiastically adopted partnerships between government, non
      government and industry. In this article, we focus on the tactics employed by
      industry bodies to further their cause in a range of fields that are
      characterized by risk and contestation. We describe the nature of the alliances
      and interactions between commercial, scientific and government groups whose
      stated aim is to improve Australia's diet. Our analysis shows that these
      partnerships have been guided less by the ethos of the Ottawa Charter and more by
      the interests of the various parties: namely the food industry's need for
      credibility in making health claims, the financial imperatives of professional
      bodies and scientists whose public funding is inadequate, and government
      endorsement of public-private partnerships as the preferred mechanism for service
      delivery. The symbiotic relationship that is emerging between segments of the
      food industry and the nutrition professions raises questions about the
      independence of the dietary advice being given to consumers. We conclude by
      arguing for a research programme to investigate the consequences of intersectoral
      partnerships on the nutritional status of the population.

PMID- 14976168
TI  - Measuring the 'obesogenic' food environment in New Zealand primary schools.
AB  - Childhood obesity is an increasing health problem in New Zealand and many other
      countries. Information is needed to guide interventions that reduce the
      'obesogenic' (obesity-promoting) elements of school environments. The aim of this
      study was to identify and measure the obesogenic elements of the school
      environment and the canteen sales of energy-dense foods and drinks. A self
      completion questionnaire was developed for assessing each school's nutrition
      environment and mailed to a stratified random sample of New Zealand schools. The
      responses from primary schools (n = 200, response rate 61%) were analysed. Only
      15.5% of schools had purpose-built canteen facilities and over half ran a food
      service for profit (31% profit to the school, 24.5% profit for the contractors).
      Only 16.5% of schools had a food policy, although 91% of those rated the policy
      as effective or very effective. The most commonly available foods for sale were
      pies (79%), juice (57%) and sausage rolls (54.5%). Filled rolls were the most
      expensive item (mean dollars 1.79) and fruit the least expensive (mean dollars
      0.47). The ratio of 'less healthy' to 'more healthy' main choices was 5.6:1, for
      snacks it was 9.3:1 and for drinks it was 1.4:1. In contrast, approximately 60%
      of respondents said that nutrition was a priority for the school. Only 50% felt
      there was management support for healthy food choices and only 39% agreed that
      mainly nutritious food was offered by the food service. 'Less healthy' choices
      dominated food sales by more than 2:1, with pies being the top selling item
      (>55000 per week). We found that the food environment was not conducive to
      healthy food choices for the children at New Zealand schools and that this was
      reflected in the high sales of relatively unhealthy foods from the school food
      services. Programmes that improve school food through policies, availability,
      prices and school ethos are urgently needed.

PMID- 14976169
TI  - The Dutch Heart Health community intervention 'Hartslag Limburg': results of an
      effect study at individual level.
AB  - 'Hartslag Limburg' (Dutch for Heartbeat Limburg), a regional cardiovascular
      diseases (CVD) prevention program, integrates a community strategy and a high
      risk strategy to reduce CVD risk behaviors. The present paper focuses on the
      effects of the community intervention on fat intake and physical activity. The
      project was based on community organization principles and health education
      theories and methods. In order to implement the intervention, nine local Health
      Committees were set up, each organizing activities that facilitate and encourage
      people to adopt a healthier lifestyle. A pre-test-post-test control group design
      with two post-tests was used to evaluate the intervention. At baseline,
      representative random cohort research samples were selected in the Maastricht
      region and in a control region. Data on fat intake and physical activity, and on
      the psychosocial determinants of these behaviors, were gathered by means of mail
      surveys. The present study indicates that the intervention had a significant
      effect on fat reduction, especially among respondents aged <or=48 years (median
      age). Respondents in the Maastricht region were also more realistic about their
      fat intake at post-test as compared with the control region. Only a limited
      effect on intentions to increase physical activity was found.

PMID- 14976170
TI  - Health benefits of Tai Chi exercise: improved balance and blood pressure in
      middle-aged women.
AB  - Tai Chi has been widely practiced as a Chinese martial art that focuses on slow
      sequential movements, providing a smooth, continuous and low intensity activity.
      It has been promoted to improve balance and strength and to reduce falls in the
      elderly, especially those 'at risk'. The potential benefits in healthy younger
      age cohorts and for wider aspects of health have received less attention. The
      present study documented prospective changes in balance and vascular responses
      for a community sample of middle-aged women. Seventeen relatively sedentary but
      healthy normotensive women aged 33-55 years were recruited into a three times per
      week, 12-week Tai Chi exercise programme. A further 17 sedentary subjects matched
      for age and body size were recruited as a control group. Dynamic balance measured
      by the Functional Reach Test was significantly improved following Tai Chi, with
      significant decreases in both mean systolic (9.71 mmHg) and diastolic (7.53 mmHg)
      blood pressure. The data confirm that Tai Chi exercise can be a good choice of
      exercise for middle-aged adults, with potential benefits for ageing as well as
      the aged.

PMID- 14976171
TI  - Defining and operationalizing capacity for heart health promotion in Nova Scotia,
      Canada.
AB  - This paper presents an operational definition of capacity building for heart
      health promotion, instruments developed to measure heart health capacity, and
      baseline results of capacity for 20 organizations. Qualitative and quantitative
      research methods were used to collect data. Three instruments were developed to
      measure organizational capacity for heart health promotion: a survey of community
      agencies involved in heart health, a questionnaire of organizational practices
      supportive of heart health promotion, and an interview guide that focused on
      factors influencing heart health promotion. These instruments proved effective
      and informed the development of a comprehensive framework for heart health
      promotion.

PMID- 14976172
TI  - Issues of participation, ownership and empowerment in a community development
      programme: tackling smoking in a low-income area in Scotland.
AB  - Founded on community development principles and practice, the 'Breathing Space'
      initiative aimed to produce a significant shift in community norms towards non
      toleration and non-practice of smoking in a low-income area in Edinburgh,
      Scotland. The effectiveness of Breathing Space was evaluated using a quasi
      experimental design, which incorporated a process evaluation in order to provide
      a description of the development and implementation of the intervention. Drawing
      on qualitative data from the process evaluation, this paper explores the varied
      and sometimes competing understandings of the endeavour held by those
      implementing the intervention. The paper examines the principles that underpin
      health promotion in the community setting, particularly the concepts of
      ownership, empowerment and participation, and their differential interpretation
      and employment by participants. The data illustrate how these varied
      understandings had implications for the joint planning and implementation of
      Breathing Space objectives. In addition, the different understandings raise
      questions about the appropriateness and viability of utilizing community
      development approaches in this context.

PMID- 14976173
TI  - Evaluation of a health promotion programme to prevent the misuse of androgenic
      anabolic steroids among Swedish adolescents.
AB  - The aim of this study was to design an appearance programme in order to prevent
      the misuse of androgenic anabolic steroids among adolescents and to evaluate the
      adolescents' perception of this programme. The study was performed in all schools
      in a primary health care area on the south west coast of Sweden. The intervention
      targeted all 16- and 17-year-old males and females (n = 921). The intervention
      and evaluation were completed by 451 boys. The strategy of the appearance
      programme was to create awareness of and to discuss attitudes towards steroid
      hormones among these adolescents. Youth leaders and health workers, who discussed
      these subjects with adolescents over a period of 2 years, carried out the
      intervention programme. The perception of the programme was analysed anonymously
      using questionnaires. Effects on the total population of youths were assessed by
      two cross-sectional surveys. The intervention programme was well received by the
      adolescents. The misuse of androgenic anabolic steroids had a tendency to
      decrease after the appearance programme. We demonstrated a method for involving
      the community in an appearance programme to reduce misuse of anabolic steroids
      and showed that youth were sensitive to our discussions about appearance and
      attitudes. This study indicates that drug abuse among adolescents can be
      decreased by health promotion activities, such as group discussions. Controlled
      studies are needed before the results of this appearance programme can be
      generalized.

PMID- 14976174
TI  - A model HIV/AIDS risk reduction programme in the Philippines: a comprehensive
      community-based approach through participatory action research.
AB  - A 3-year, longitudinal, quasi-experimental study using participatory action
      research (PAR) was conducted to determine the feasibility and efficiency of an
      expanded sexually transmitted infection (STI) HIV/AIDS prevention program among
      diverse high-risk male heterosexual populations in the southern Philippines. A
      total of 3389 participants ( approximately 200 males from each of 18 study
      groups) were recruited, and 221 were trained as peer counselors to develop
      educational materials and reinforce safe sexual practices among their peers.
      Condom usage (36.10% to 38.70% to 46.31%), attitudes towards condoms (21.67% to
      24.55% to 25.15%) and knowledge about HIV/STI transmission (41.87% to 42.19% to
      33.31%) increased significantly from baseline to post-test and 6-month follow up,
      respectively (p < 0.01). Furthermore, the reported STI incidence decreased
      significantly (7.4% to 4.6% to 2.4%, respectively). Changes differed
      significantly between the intervention and control group at post-test and follow
      up (p < 0.01). These findings illustrate the appropriateness of using PAR
      methodology in promoting and sustaining positive behavior change.

PMID- 14976175
TI  - Capacity and transparency of potable water regulation in Tijuana, Mexico:
      challenges for ensuring water quality at community level.
AB  - The ability of public institutions to provide efficient and equitable potable
      water services is key to reducing water-borne diseases, one of the leading causes
      of morbidity and mortality in the developing world. In this article, a case study
      of potable water and public health programs in Tijuana, Mexico, is used to direct
      attention to practical examples of policy and institutional incapacities. A
      qualitative methodology was used to gain access to local context and the formal
      and informal actions of the key informants. This paper concludes that public
      health agencies are creating the illusion of program action through disease
      surveillance, however capacity gaps demonstrate that institutional policy is not
      pragmatically reflected on the local community level. Political client-patron
      relationships are used to circumvent bureaucratic barriers and distribute
      resources at the local level. This raises the question of whether further
      accountability will bring the much-expected equitable distribution of public
      goods in the developing world.

PMID- 14976176
TI  - Issues in measuring health promotion capacity in Canada: a multi-province
      perspective.
AB  - Significant international progress has been made researching and addressing the
      economic and social burden of cardiovascular disease, advanced particularly by
      international conferences and subsequent declarations, and the Canadian Heart
      Health Initiative (CHHI). The implementation focus of the CHHI on building
      capacity for heart health promotion is paralleled by efforts to measure capacity.
      Through the collective experience of Heart Health Programs in Nova Scotia,
      Saskatchewan, Alberta and British Columbia, critical issues in measuring health
      promotion capacity are identified and strategies for addressing them are
      presented. The provincial contexts for the programs vary, as do the
      conceptualizations of capacity and intervention strategies to build capacity.
      Yet, despite such differences across provinces, shared issues influencing
      measuring capacity number many. These include: multiple understandings of terms;
      evolving understanding of capacity; invisibility of capacity building; detecting
      change within a dynamic system; staff turnover; time course required for change;
      attribution for change in capacity; understanding a process through 'snap-shot'
      measurements; lack of existing 'gold standard' measurement tools; validity and
      credibility of instruments; evolving nature of measurement tools; gathering
      perspectives from multiple levels within organizations; dealing with conflicting
      perspectives; and managing and disseminating sensitive data. A number of
      strategies have been devised or adopted to address measurement issues, ranging
      from adopting participatory processes to the development of monitoring systems.
      Understanding and addressing issues in measuring capacity deserve attention as
      they may be potent influences in the dynamic interplay between research and
      intervention in the process of capacity building in the context of health
      promotion generally, and/or heart health specifically.

PMID- 14976177
TI  - Unsafe injections in low-income country health settings: need for injection
      safety promotion to prevent the spread of blood-borne viruses.
AB  - Injections are one of the most frequently used medical procedures. The World
      Health Organization (WHO) estimates that 12 billion injections are given
      annually, 5% of which are administered for immunization and 95% for curative
      purposes. Unsafe injection practices (especially needle and syringe re-use) are
      commonplace in low-income country health settings, and place both staff and
      patients at risk of infection with blood-borne viruses (BBVs). It is estimated
      that up to 160000 human immunodeficiency virus (HIV), 4.7 million hepatitis C and
      16 million hepatitis B infections each year are attributable to these practices.
      The problem is complex and fueled by a mixture of socio-cultural, economic and
      structural factors. An appropriate response on the part of international
      organizations, governments, health administrators, community organizations and
      health workers, including those who work in the area of HIV/AIDS prevention, has
      been slow to emerge. This paper reviews the literature relating to unsafe
      injection practices and the transmission of BBVs in low-income countries in order
      to raise awareness of the issue and the consequent need to promote injection
      safety messages amongst both consumers and providers of health care services in
      these countries. The nature and extent of unsafe injection practices, the burden
      of blood-borne viral illness attributable to unsafe injection practices, and the
      factors contributing to these practices are summarized, and possible strategies
      for promoting injection safety discussed.

PMID- 14976178
TI  - A partnership approach to health promotion: a case study from Northern Ireland.
AB  - In recent years there has been a renewal of interest in community development and
      partnership approaches in the delivery of health and social services in Northern
      Ireland. The general thrust of these approaches is that local communities can be
      organized to address health and social needs and to work with government
      agencies, voluntary bodies and local authorities in delivering services and local
      solutions to problems. Since the Ottawa Charter was launched in 1986, government
      in Northern Ireland has stressed that community development should no longer
      simply be added on to key aspects of Health and Social Services, but should
      instead be at the core of their work. There is increasing consensus that
      traditional approaches to improving health and well-being, which have focused on
      the individual, are paternalistic and have failed to tackle inequalities
      effectively. Partnerships within a community development setting have been
      heralded as a means to facilitate participation and empowerment. This paper
      outlines the policy background to community development approaches in health
      promotion and delivery in Northern Ireland. Drawing on evidence from a case study
      of a community health project it highlights the benefits and difficulties with
      this approach. The findings suggest that partnerships can positively influence a
      community's health status, but in order to be effective they require effective
      planning and long-term commitment from both the state and the local community.

PMID- 14976179
TI  - Social inclusion/exclusion: dancing the dialectic.
AB  - The last decade has seen many of the 'community' concepts in health (community
      empowerment, community capacity) replaced by 'social' concepts (social capital,
      social cohesion). The continuous re-labelling of roughly similar phenomena may be
      a necessary stratagem to attract attention to the economic and power inequalities
      that arise from undisciplined markets. Social concepts also have an advantage
      over community ones by directing that attention to higher orders of political
      systems. The latest construct being wielded by health practitioners, researchers
      and policy-makers are the twinned concepts of social inclusion and social
      exclusion. These represent a conceptual sophistication over social capital and
      social cohesion. Like their predecessors, however, there are risks in their
      adoption without a critical examination of the premises that underpin them. For
      example, how can one 'include' people and groups into structured systems that
      have systematically 'excluded' them in the first place? The cautions expressed in
      this article do not dissuade use of the concepts. Their utility, however,
      particularly at a time when not only inequalities, but also their rate of growth,
      is increasing, requires careful questioning.

PMID- 14976180
TI  - The sustainability of health promotion interventions for different levels of
      social organization.
AB  - In health promotion, enthusiasm for sustainability has frequently overshadowed
      critical reflection with regard to whether this aim is warranted, let alone
      feasible. Consequently, the not insubstantial body of literature on
      sustainability in health promotion is not particularly helpful to decision
      makers. In this paper we seek to provide some guidance for the development of
      sustainability for health promotion interventions, arguing that it is necessary
      to be able to differentiate between (i). levels of social organization which are
      the focus of change, (ii). the programmes and agencies which are the means
      employed to achieve change, and (iii). the outcomes or effects that are achieved.
      Furthermore, funding allocations need to be congruent with programme
      characteristics if one is serious about achieving sustainability.

PMID- 14976183
TI  - RGS2 binds directly and selectively to the M1 muscarinic acetylcholine receptor
      third intracellular loop to modulate Gq/11alpha signaling.
AB  - RGS proteins serve as GTPase-activating proteins and/or effector antagonists to
      modulate Galpha signaling events. In live cells, members of the B/R4 subfamily of
      RGS proteins selectively modulate G protein signaling depending on the associated
      receptor (GPCR). Here we examine whether GPCRs selectively recruit RGS proteins
      to modulate linked G protein signaling. We report the novel finding that RGS2
      binds directly to the third intracellular (i3) loop of the G(q/11)-coupled M1
      muscarinic cholinergic receptor (M1 mAChR; M1i3). This interaction is selective
      because closely related RGS16 does not bind M1i3, and neither RGS2 nor RGS16
      binds to the G(i/o)-coupled M2i3 loop. When expressed in cells, RGS2 and M1 mAChR
      co-localize to the plasma membrane whereas RGS16 does not. The N-terminal region
      of RGS2 is both necessary and sufficient for binding to M1i3, and RGS2 forms a
      stable heterotrimeric complex with both activated G(q)alpha and M1i3. RGS2
      potently inhibits M1 mAChR-mediated phosphoinositide hydrolysis in cell membranes
      by acting as an effector antagonist. Deletion of the N terminus abolishes this
      effector antagonist activity of RGS2 but not its GTPase-activating protein
      activity toward G(11)alpha in membranes. These findings predict a model where the
      i3 loops of GPCRs selectively recruit specific RGS protein(s) via their N termini
      to regulate the linked G protein. Consistent with this model, we find that the i3
      loops of the mAChR subtypes (M1-M5) exhibit differential profiles for binding
      distinct B/R4 RGS family members, indicating that this novel mechanism for GPCR
      modulation of RGS signaling may generally extend to other receptors and RGS
      proteins.

PMID- 14976184
TI  - Myeloid Elf-1-like factor, an ETS transcription factor, up-regulates lysozyme
      transcription in epithelial cells through interaction with promyelocytic leukemia
      protein.
AB  - Myeloid elf-1-like factor (MEF) or Elf4, which is a member of the ETS
      transcription factor family, up-regulates the basal expression of lysozyme gene
      in epithelial cells and is constitutively localized in the nucleus. The mammalian
      cell nucleus is organized into distinct nuclear domains or compartments that are
      essential for diverse physiological processes. Promyelocytic leukemia (PML)
      nuclear body or nuclear domain 10 is one of the nuclear domains and is involved
      in tumor suppression and regulation of transcription. Here, we investigate the
      role of PML nuclear body in MEF transactivation. We show that PML, but not Sp100,
      induced the accumulation of MEF in PML nuclear bodies and that MEF and PML
      physically interacted. This interaction stimulated MEF transcriptional activity,
      resulting in the up-regulation of endogenous lysozyme expression. Amino acids 348
      517 of MEF were required for the accumulation of MEF in PML nuclear bodies and up
      regulation of lysozyme transcription, which is enhanced by PML. Moreover, the C
      terminal region of MEF spanning amino acids 477-517 was the putative region
      required for interaction between MEF and PML as determined with the use of the
      mammalian two-hybrid system. In addition, heat-shock treatment induced the
      accumulation of MEF in endogenous PML nuclear bodies and enhanced MEF
      transactivation of lysozyme gene. Thus, the recruitment of MEF to PML nuclear
      bodies may partly regulate lysozyme transcription in epithelial cells.

PMID- 14976185
TI  - ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel
      subunit in sensory neurons via the partner protein PICK-1.
AB  - ASIC3, an acid-sensing ion channel subunit expressed essentially in sensory
      neurons, has been proposed to be involved in pain. We show here for the first
      time that native ASIC3-like currents were increased in cultured dorsal root
      ganglion (DRG) neurons following protein kinase C (PKC) stimulation. This
      increase was induced by the phorbol ester PDBu and by pain mediators, such as
      serotonin, which are known to activate the PKC pathway through their binding to G
      protein-coupled receptors. We demonstrate that this regulation involves the
      silent ASIC2b subunit, an ASIC subunit also expressed in sensory neurons. Indeed,
      heteromultimeric ASIC3/ASIC2b channels, but not homomeric ASIC3 channels, are
      positively regulated by PKC. The increase of ASIC3/ASIC2b current is accompanied
      by a shift in its pH dependence toward more physiological pH values and may lead
      to an increase of sensory neuron excitability. This regulation by PKC requires
      PICK-1 (protein interacting with C kinase), a PDZ domain-containing protein,
      which interacts with the ASIC2b C terminus.

PMID- 14976186
TI  - Unique and selective effects of five Ets family members, Elf3, Ets1, Ets2, PEA3,
      and PU.1, on the promoter of the type II transforming growth factor-beta receptor
      gene.
AB  - Previous studies have shown that the promoter of the type II TGF-beta receptor
      gene (TbetaR-II) is strongly stimulated by Elf3, a member of the Ets
      transcription factor family. The TbetaR-II gene behaves as a tumor suppressor and
      it is expressed in nearly all cell types, whereas Elf3 is expressed primarily in
      epithelial cells. Hence, the TbetaR-II gene is likely to be regulated by other
      Ets proteins in nonepithelial cells. In this study, we examined the effects of
      four other Ets family members (Ets1, Ets2, PEA3, and PU.1) on TbetaR-II
      promoter/reporter constructs that contain the two essential ets sites of this
      gene. These studies employed F9 embryonal carcinoma cells and their
      differentiated cells, because transcription of the TbetaR-II gene increases after
      F9 cells differentiate. Here we demonstrate that Ets2, which is expressed in F9
      differentiated cells along with Elf3, does not stimulate or bind to the TbetaR-II
      promoter in these cells. In contrast, PEA3 stimulates the TbetaR-II promoter in
      F9-differentiated cells, but it inhibits this promoter in F9 cells. Thus, the
      effects of PEA3 on the TbetaR-II promoter are cell context-dependent. We also
      show that the effects of Elf3 are cell context-dependent. Elf3 strongly
      stimulates the TbetaR-II promoter in F9-differentiated cells, but not in F9
      cells. In contrast to Elf3 and PEA3, Ets1 strongly stimulates this promoter in
      both F9 cells and F9-differentiated cells. Finally, we show that PU.1 exerts
      little or no effect on the activity of the TbetaR-II promoter. Together, our
      findings indicate that Elf3 is not the only Ets protein capable of stimulating
      the TbetaR-II promoter. Importantly, our findings also indicate that each of the
      five Ets proteins influences the TbetaR-II promoter in a unique manner because of
      important differences in their biochemical properties or their patterns of
      cellular expression.

PMID- 14976187
TI  - Mobilization of adenine nucleotide translocators as molecular bases of the
      biochemical threshold effect observed in mitochondrial diseases.
AB  - The existence of a biochemical threshold effect in the metabolic expression of
      oxidative phosphorylation deficiencies has considerable implications for the
      understanding of mitochondrial bioenergetics and the study of mitochondrial
      diseases. However, the molecular bases of this phenomenon remain unclear. We
      report here a new mechanism to explain this threshold effect, based on a reserve
      of enzymes not initially participating in the respiratory rate that can be
      activated either to respond to a flux increase or to compensate for a defect
      induced by a mutation. We show that this mobilization occurs through 1) the
      assembly of inactive adenine nucleotide translocator isoform 1 subunits into
      oligomeric active carriers or 2) conformational changes in the adenine nucleotide
      translocator isoform 1 in a permeability transition pore-like structure. We
      discuss how these transitions are sensitive to the steady state of oxidative
      phosphorylation functioning or tissue and analyze their consequences on the
      threshold effect.

PMID- 14976188
TI  - Activation and repression of interleukin-12 p40 transcription by erythroid
      Kruppel-like factor in macrophages.
AB  - Transcription of interleukin (IL)-12 p40 in myeloid cells is attributed to the
      recruitment of multiple activated transcription factors such as nuclear factor
      kappaB (NFkappaB), CCAAT enhancer-binding protein beta, ets-2, PU.1, and so
      forth. We now provide the first description of the human erythroid Kruppel-like
      factor (EKLF) in human primary macrophages and identify the role of EKLF in IL-12
      p40 expression. EKLF-specific binding to the CACCC element (-224 to -220) on the
      human IL-12 p40 promoter was observed in resting human primary macrophages.
      Functional analysis of the CACCC element revealed a dependent role for EKLF
      binding in activating IL-12 p40 transcription in resting RAW264.7 cells, whereas
      EKLF overexpression in the presence or absence of this element repressed IL-12
      p40 transcription in interferon gamma/lipopolysaccharide-stimulated RAW264.7
      cells. Murine endogenous IL-12 p40 mRNA was consistently induced by overexpressed
      EKLF in resting RAW264.7 cells, whereas EKLF suppressed IL-12 p40 expression in
      activated RAW264.7 cells. Modulation of nuclear binding activities at the IL-12
      p40 NFkappaB half-site was induced by EKLF for down-regulation of IL-12 p40
      transcription in activated RAW264.7 cells, but no effect of EKLF on NFkappaB
      activity was observed in resting RAW264.7 cells. Taken together, we identify EKLF
      as a transcription factor in macrophages able to regulate IL-12 p40 transcription
      depending on the cellular activation status. The bifunctional control of IL-12
      p40 by EKLF and its modulation of NFkappaB support a potential function for this
      factor in orchestrating IL-12 p40 production in macrophages.

PMID- 14976189
TI  - The CD20 calcium channel is localized to microvilli and constitutively associated
      with membrane rafts: antibody binding increases the affinity of the association
      through an epitope-dependent cross-linking-independent mechanism.
AB  - CD20 is a B cell-specific membrane protein that functions in store-operated
      calcium entry and serves as a useful target for antibody-mediated therapeutic
      depletion of B cells. Antibody binding to CD20 induces a diversity of biological
      effects, some of which are dependent on lipid rafts. Rafts are isolated as low
      density detergent-resistant membranes, initially characterized using Triton X
      100. We have previously reported that CD20 is soluble in 1% Triton but that
      antibodies induce the association of CD20 with Triton-resistant rafts. However,
      by using several other detergents to isolate rafts and by microscopic co
      localization with a glycosylphosphatidylinositol-linked protein, we show in this
      report that CD20 is constitutively raft-associated. CD20 was distributed in a
      punctate pattern on the cell surface as visualized by fluorescence imaging and
      was also localized to microvilli by electron microscopy. The mechanism underlying
      antibody-induced association of CD20 with Triton-resistant rafts was investigated
      and found not to require cellular ATP, kinase activity, actin polymerization, or
      antibody cross-linking but was dependent on the epitope recognized. Thus,
      antibody-induced insolubility in 1% Triton most likely reflects a transition from
      relatively weak to strong raft association that occurs as a result of a
      conformational change in the CD20 protein.

PMID- 14976190
TI  - Inhibitors of protein kinase C (PKC) prevent activated transcription: role of
      events downstream of NF-kappaB DNA binding.
AB  - In pulmonary A549 cells, the protein kinase C (PKC) inhibitor, Ro 31-8220, and
      the phosphotidylcholine-specific phospholipase C inhibitor, D609, prevent NF
      kappaB-dependent transcription, yet NF-kappaB DNA binding is unaffected
      (Bergmann, M., Hart, L., Lindsay, M., Barnes, P. J., and Newton, R. (1998) J.
      Biol. Chem. 273, 6607-6610). We now show that this effect also occurs in BEAS-2B
      bronchial epithelial cells as well as with other PKC inhibitors (Go 6976,
      GF109203X, and calphostin C) in A549 cells. Similarly, phorbol ester, a
      diacylglycerol mimetic, activates NF-kappaB-dependent transcription and
      potentiates tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB-dependent
      transcription, yet unlike TNFalpha, poorly activates IkappaB kinase (IKK)
      activity, IkappaBalpha degradation, or NF-kappaB DNA binding in both A549 and
      BEAS-2B cells. As phorbol ester-induced NF-kappaB-dependent transcription was
      relatively insensitive to the proteasome inhibitor, MG-132, PKC may affect NF
      kappaB-dependent transcription via mechanisms other than the core IKK-IkappaB
      pathway. This is supported by Gal4 one hybrid analysis of p65/RelA
      transactivation, which was potentiated by TNFalpha and phorbol ester and was
      inhibited by Ro 31-8220 and D609. Additionally, a number of PKC isoforms,
      particularly the novel isoform PKCepsilon, induced p65/RelA transactivation.
      Phosphorylation of p65/RelA and cAMP-responsive element-binding protein (CREB)
      binding protein (CBP) was increased by TNFalpha treatment and, in the case of
      CBP, was prevented by Ro 31-8220 or D609. However, p65/RelA-CBP interactions were
      unaffected by either compound. As this effect was not limited to NF-kappaB, but
      was a more general feature of inducible gene transcription, we suggest PKC
      isoforms may provide a point of intervention in diseases such as inflammation, or
      cancer, where activated gene expression is prominent.

PMID- 14976191
TI  - Structure-function analysis of PrsA reveals roles for the parvulin-like and
      flanking N- and C-terminal domains in protein folding and secretion in Bacillus
      subtilis.
AB  - The PrsA protein of Bacillus subtilis is an essential membrane-bound lipoprotein
      that is assumed to assist post-translocational folding of exported proteins and
      stabilize them in the compartment between the cytoplasmic membrane and cell wall.
      This folding activity is consistent with the homology of a segment of PrsA with
      parvulin-type peptidyl-prolyl cis/trans isomerases (PPIase). In this study,
      molecular modeling showed that the parvulin-like region can adopt a parvulin-type
      fold with structurally conserved active site residues. PrsA exhibits PPIase
      activity in a manner dependent on the parvulin-like domain. We constructed
      deletion, peptide insertion, and amino acid substitution mutations and
      demonstrated that the parvulin-like domain as well as flanking N- and C-terminal
      domains are essential for in vivo PrsA function in protein secretion and growth.
      Surprisingly, none of the predicted active site residues of the parvulin-like
      domain was essential for growth and protein secretion, although several active
      site mutations reduced or abolished the PPIase activity or the ability of PrsA to
      catalyze proline-limited protein folding in vitro. Our results indicate that PrsA
      is a PPIase, but the essential role in vivo seems to depend on some non-PPIase
      activity of both the parvulin-like and flanking domains.

PMID- 14976192
TI  - An arginine-histone methyltransferase, CARMER, coordinates ecdysone-mediated
      apoptosis in Drosophila cells.
AB  - Developmentally programmed cell death is regulated by a balance between pro- and
      anti-death signaling. During Drosophila metamorphosis, the removal of larval
      tissues is dependent on the steroid hormone ecdysone, which controls the levels
      of pro- and anti-death molecules. Ecdysone binds to its heterodimeric receptor
      ecdysone receptor/ultraspiracle to mediate transcription of primary response
      genes. Here we show that CARMER, an arginine-histone methyltransferase, is
      critical in coordinating ecdysone-induced expression of Drosophila cell death
      genes. Ablation of CARMER blocks ecdysone-induced cell death in Drosophila cells,
      but not apoptosis induced by cell stress. We demonstrate that CARMER associates
      with the ecdysone receptor complex and modulates the ecdysone-induced
      transcription of a number of apoptotic genes. Thus, the chromatin-modifying
      protein, CARMER, modulates cell death by controlling the hormone-dependent
      expression of the core cell death machinery.

PMID- 14976193
TI  - A common cross-species function for the double epidermal growth factor-like
      modules of the highly divergent plasmodium surface proteins MSP-1 and MSP-8.
AB  - An understanding of structural and functional constraints on the C-terminal
      double epidermal growth factor (EGF)-like modules of merozoite surface protein
      (MSP)-1 and related proteins is of importance to the development of these
      molecules as malaria vaccines and drug targets. Using allelic replacement, we
      show that Plasmodium falciparum parasites can invade erythrocytes and grow
      efficiently in the absence of an MSP-1 protein with authentic MSP-1 EGF domains.
      In this mutant parasite line, the MSP-1 EGFs were replaced by the corresponding
      double EGF module from P. berghei MSP-8, the sequence of which shares only low
      identity with its MSP-1 counterpart. Hence, the C-terminal EGF domains of at
      least some Plasmodium surface proteins appear to perform the same function in
      asexual blood-stage development. Mapping the surface location of the few residues
      that are common to these functionally complementary EGF modules revealed the
      presence of a highly conserved pocket of potential functional significance. In
      contrast to MSP-8, an even more divergent double EGF module, that from the sexual
      stage protein PbS25, was not capable of complementing MSP-1 EGF function. More
      surprisingly, two chimeric double EGF modules comprising hybrids of the EGF
      domains from P. falciparum and P. chabaudi MSP-1 were also not capable of
      replacing the P. falciparum MSP-1 EGF module. Together, these data suggest that
      although the MSP-1 EGFs can accommodate extensive sequence diversity, there
      appear to be constraints that may restrict the simple accumulation of point
      mutations in the face of immune pressure in the field.

PMID- 14976194
TI  - Delineation of the HLA-DR region and the residues involved in the association
      with the cytoskeleton.
AB  - Whereas the association of major histocompatibility complex (MHC) class II
      molecules with the cytoskeleton and their recruitment into lipid rafts play a
      critical role during cognate T/antigen-presenting cell interactions, MHC class II
      induced signals, regions, and residues involved in their association and
      recruitment have not yet been fully deciphered. In this study, we show that
      oligomerization of HLA-DR molecules induces their association with the
      cytoskeleton and their recruitment into lipid rafts. The association of
      oligomerized HLA-DR molecules with the cytoskeleton and their recruitment into
      lipid rafts occur independently. Furthermore, the association with the
      cytoskeleton is HLA-DR-specific, since oligomerization of HLA-DP triggers its
      recruitment only into lipid rafts. HLA-DR molecules devoid of both alpha and beta
      cytoplasmic tails did not associate with the cytoskeleton, but their recruitment
      into lipid rafts was unimpeded. Deletion of either the alpha or beta cytoplasmic
      tail did not affect the association of HLA-DR with the cytoskeleton and/or
      recruitment into lipid rafts. HLA-DR molecules that were devoid of the alpha
      cytoplasmic chain and that had their beta cytoplasmic chain replaced with the HLA
      DP beta chain or with a beta chain in which the residues at positions Gly(226)
      His(227)-Ser(228) were substituted by alanine no longer associated with the
      cytoskeleton. They were, however, still recruited into lipid rafts. Together,
      these results support the involvement of different regions of the cytoplasmic
      tails in the association and the recruitment of HLA-DR into different
      compartments. The differential behavior of HLA-DP and -DR with respect to their
      association with the cytoskeleton may explain the previously described difference
      in their transduced signals.

PMID- 14976195
TI  - Expression cloning of a human cDNA restoring sphingomyelin synthesis and cell
      growth in sphingomyelin synthase-defective lymphoid cells.
AB  - Sphingomyelin (SM) synthase has been assumed to be involved in both cell death
      and survival by regulating pro-apoptotic mediator ceramide and pro-survival
      mediator diacylglycerol. However, its precise functions are ambiguous due to the
      lack of molecular cloning of SM synthase gene(s). We isolated WR19L/Fas-SM(-)
      mouse lymphoid cells, which show a defect of SM at the plasma membrane due to the
      lack of SM synthase activity and resistance to cell death induced by an SM
      directed cytolytic protein lysenin. WR19L/Fas-SM(-) cells were also highly
      susceptible to methyl-beta-cyclodextrin (MbetaCD) as compared with the WR19L/Fas
      SM(+) cells, which are capable of SM synthesis. By expression cloning method
      using WR19L/Fas-SM(-) cells and MbetaCD-based selection, we have succeeded in
      cloning of a human cDNA responsible for SM synthase activity. The cDNA encodes a
      peptide of 413 amino acids named SMS1 (putative molecular mass, 48.6 kDa), which
      contains a sterile alpha motif domain near the N-terminal region and four
      predicted transmembrane domains. WR19L/Fas-SM(-) cells expressing SMS1 cDNA
      (WR19L/Fas-SMS1) restored the resistance against MbetaCD, the accumulation of SM
      at the plasma membrane, and SM synthesis by transferring phosphocholine from
      phosphatidylcholine to ceramide. Furthermore, WR19L/Fas-SMS1 cells, as well as
      WR19L/Fas-SM(-) cells supplemented with exogenous SM, restored cell growth
      ability in serum-free conditions, where the growth of WR19L/Fas-SM(-) cells was
      severely inhibited. The results suggest that SMS1 is responsible for SM synthase
      activity in mammalian cells and plays a critical role in cell growth of mouse
      lymphoid cells.

PMID- 14976196
TI  - Glyoxalase II of African trypanosomes is trypanothione-dependent.
AB  - The glyoxalase system is a ubiquitous pathway catalyzing the glutathione
      dependent detoxication of ketoaldehydes such as methylglyoxal, which is mainly
      formed as a by-product of glycolysis. The gene encoding a glyoxalase II has been
      cloned from Trypanosoma brucei, the causative agent of African sleeping sickness.
      The deduced protein sequence contains the highly conserved metal binding motif
      THXHXDH but lacks three basic residues shown to fix the glutathione-thioester
      substrate in the crystal structure of human glyoxalase II. Recombinant T. brucei
      glyoxalase II hydrolyzes lactoylglutathione, but does not show saturation
      kinetics up to 5 mm with the classical substrate of glyoxalases II. Instead, the
      parasite enzyme strongly prefers thioesters of trypanothione
      (bis(glutathionyl)spermidine), which were prepared from methylglyoxal and
      trypanothione and analyzed by high performance liquid chromatography and mass
      spectrometry. Mono-(lactoyl)trypanothione and bis-(lactoyl)trypanothione are
      hydrolyzed by T. brucei glyoxalase II with k(cat)/K(m) values of 5 x 10(5) m(-1)
      s(-1) and 7 x 10(5) m(-1) s(-1), respectively, yielding d-lactate and
      regenerating trypanothione. Glyoxalase II occurs in the mammalian bloodstream and
      insect procyclic form of T. brucei and is the first glyoxalase II of the order of
      Kinetoplastida characterized so far. Our results show that the glyoxalase system
      is another pathway in which the nearly ubiquitous glutathione is replaced by the
      unique trypanothione in trypanosomatids.

PMID- 14976197
TI  - Regulation of immature protein dynamics in the endoplasmic reticulum.
AB  - The quality of nascent protein folding in vivo is influenced by the microdynamics
      of the proteins. Excessive collisions between proteins may lead to terminal
      misfolding, and the frequency of protein interactions with molecular chaperones
      determines their folding rates. However, it is unclear how immature protein
      dynamics are regulated. In this study, we analyzed the diffusion of immature
      tyrosinase in the endoplasmic reticulum (ER) of non-pigmented cells by taking
      advantage of the thermal sensitivity of the tyrosinase. The diffusion of
      tyrosinase tagged with yellow fluorescence protein (YFP) in living cells was
      directly measured using fluorescent correlation spectroscopy. The diffusion of
      folded tyrosinase in the ER of cells treated with brefeldin A, as measured by
      fluorescent correlation spectroscopy, was critically affected by the expression
      level of tyrosinase-YFP. Under defined conditions in which random diffusional
      motion of folded protein was allowed, we found that the millisecond-order
      diffusion rate observed for folded tyrosinase almost disappeared for the
      misfolded molecules synthesized at a nonpermissive high temperature. This was not
      because of enhanced aggregation at the high temperature, as terminally misfolded
      tyrosinase synthesized in the absence of calnexin interactions showed comparable,
      albeit slightly slower, diffusion. Yet, the thermally misfolded tyrosinase was
      not immobilized when measured by fluorescence recovery after photobleaching. In
      contrast, terminally misfolded tyrosinase synthesized in cells in which alpha
      glucosidases were inhibited showed extensive immobilization. Hence, we suggest
      that the ER represses random fluctuations of immature tyrosinase molecules while
      preventing their immobilization.

PMID- 14976198
TI  - Identification of methionine-rich clusters that regulate copper-stimulated
      endocytosis of the human Ctr1 copper transporter.
AB  - Copper uptake and subsequent delivery to copper-dependent enzymes are essential
      for many cellular processes. However, the intracellular levels of this nutrient
      must be controlled because of its potential toxicity. The hCtr1 protein functions
      in high affinity copper uptake at the plasma membrane of human cells. Recent
      studies have shown that elevated copper stimulates the endocytosis and
      degradation of the hCtr1 protein, and this response is likely an important
      homeostatic mechanism that prevents the overaccumulation of copper. The domains
      of hCtr1 involved in copper-stimulated endocytosis and degradation are unknown.
      In this study we examined the importance of potential copper-binding sequences in
      the extracellular domain and a conserved transmembrane (150)MXXXM(154) motif for
      copper-stimulated endocytosis and degradation of hCtr1. The endocytic response of
      hCtr1 to low copper concentrations required an amino-terminal methionine cluster
      ((40)MMMMPM(45)) closest to the transmembrane region. However, this cluster was
      not required for the endocytic response to higher copper levels, suggesting this
      motif may function as a high affinity copper-sensing domain. Moreover, the
      transmembrane (150)MXXXM(154) motif was absolutely required for copper-stimulated
      endocytosis and degradation of hCtr1 even under high copper concentrations.
      Together with previous studies demonstrating a role for these motifs in high
      affinity copper transport activity, our findings suggest common biochemical
      mechanisms regulate both transport and trafficking functions of hCtr1.

PMID- 14976199
TI  - Mutations at the S1 sites of methionine aminopeptidases from Escherichia coli and
      Homo sapiens reveal the residues critical for substrate specificity.
AB  - Methionine aminopeptidase (MetAP) catalyzes the removal of methionine from newly
      synthesized polypeptides. MetAP carries out this cleavage with high precision,
      and Met is the only natural amino acid residue at the N terminus that is
      accepted, although type I and type II MetAPs use two different sets of residues
      to form the hydrophobic S1 site. Characteristics of the S1 binding pocket in type
      I MetAP were investigated by systematic mutation of each of the seven S1 residues
      in Escherichia coli MetAP type I (EcMetAP1) and human MetAP type I (HsMetAP1). We
      found that Tyr-65 and Trp-221 in EcMetAP1, as well as the corresponding residues
      Phe-197 and Trp-352 in HsMetAP1, were essential for the hydrolysis of a
      thiopeptolide substrate, Met-S-Gly-Phe. Mutation of Phe-191 to Ala in HsMetAP1
      caused inactivity in contrast to the full activity of EcMetAP1(Y62A), which may
      suggest a subtle difference between the two type I enzymes. The more striking
      finding is that mutation of Cys-70 in EcMetAP1 or Cys-202 in HsMetAP1 opens up
      the S1 pocket. The thiopeptolides Leu-S-Gly-Phe and Phe-S-Gly-Phe, with
      previously unacceptable Leu or Phe as the N-terminal residue, became efficient
      substrates of EcMetAP1(C70A) and HsMetAP1(C202A). The relaxed specificity shown
      in these S1 site mutants for the N-terminal residues was confirmed by hydrolysis
      of peptide substrates and inhibition by reaction products. The structural
      features at the enzyme active site will be useful information for designing
      specific MetAP inhibitors for therapeutic applications.

PMID- 14976200
TI  - Contribution of distinct structural elements to activation of calpain by Ca2+
      ions.
AB  - The effect of Ca2+ in calpain activation is mediated via several binding sites in
      the enzyme molecule. To test the contribution of structural elements suspected to
      be part of this Ca2+ relay system, we made a site-directed mutagenesis study on
      calpains, measuring consequential changes in Ca2+ binding and Ca2+ sensitivity of
      enzyme activity. Evidence is provided for earlier suggestions that an acidic loop
      in domain III and the transducer region connecting domains III and IV are part of
      the Ca2+ relay system. Wild-type Drosophila Calpain B domain III binds two to
      three Ca2+ ions with a K(d) of 3400 microm. Phospholipids lower this value to 220
      microm. Ca2+ binding decreases in parallel with the number of mutated loop
      residues. Deletion of the entire loop abolishes binding of the ion. The Ca2+
      dependence of enzyme activity of various acidic-loop mutants of Calpain B and rat
      m-calpain suggests the importance of the loop in regulating activity. Most
      conspicuously, the replacement of two adjacent acidic residues in the N-terminal
      half of the loop evokes a dramatic decrease in the Ca2+ need of both enzymes,
      lowering half-maximal Ca2+ concentration from 8.6 to 1.3 mm for Calpain B and
      from 250 to 7 microm for m-calpain. Transducer-region mutations in m-calpain also
      facilitate Ca2+ activation with the most profound effect seen upon shortening the
      region by deletion mutagenesis. All of these data along with structural
      considerations suggest that the acidic loop and the transducer region form an
      interconnected, extended structural unit that has the capacity to integrate and
      transduce Ca2+-evoked conformational changes over a long distance. A schematic
      model of this "extended transducer" mechanism is presented.

PMID- 14976201
TI  - Polyoma enhancer activator 3, an ets transcription factor, mediates the induction
      of cyclooxygenase-2 by nitric oxide in colorectal cancer cells.
AB  - Abundant evidence supports the role of cyclooxygenase-2 (COX-2) in colorectal
      cancer. Nitric oxide (NO), a pro-inflammatory signaling factor, may regulate COX
      2 expression and activity thereby linking hyper-inflammatory states to cancer
      susceptibility. Previously we showed that NO induced COX-2 expression. Although
      NO also activated the beta-catenin.T-cell factor/lymphocyte enhancing factor
      transcriptional pathway, a direct causal link between this pathway and COX-2
      expression was not demonstrated. In this current study, we focused on NO-induced
      transcriptional activity and elucidated its role in COX-2 expression. NO donors
      stimulated the expression of peroxisome proliferator-activated receptor-delta and
      c-myc, both downstream genes of beta-catenin. They also induced the expression of
      polyoma enhancer activator 3 (PEA3) and increased its DNA-binding activity. To
      establish a role for PEA3 to beta-catenin-induced COX-2, we transfected RKO cells
      with beta-catenin and found that beta-catenin increased PEA3 expression. Also,
      there was higher PEA3 in immortal mouse colon epithelium cells (Apc(Min/)(+))
      compared with young adult mouse colon cells (Apc(+/+)). Luciferase reporter
      assays revealed that, although several transcription factors/coactivator, acting
      alone or in synergistic combination, induced COX-2 promoter activity, PEA3 was
      one of the most potent. Interestingly, NO from NO donors or generated
      endogenously from transfected inducible nitric-oxide synthase, increased
      PEA3/p300-induced COX-2 promoter activity. We also found that an ETS site (-75/
      72) and the NF-IL6 site were responsible for COX-2 activity induced by PEA3,
      PEA3/p300, and NO. Taken together, our results demonstrated that NO through beta
      catenin signaling stimulated PEA3 to increase COX-2 activity. In addition, NO
      augmented the synergistic interaction between PEA3 and CBP/p300.

PMID- 14976202
TI  - Nm23-H2 interacts with a G protein-coupled receptor to regulate its endocytosis
      through an Rac1-dependent mechanism.
AB  - G protein-coupled receptors (GPCRs) represent a vast family of transmembrane
      proteins involved in the regulation of several physiological responses. The
      thromboxane A2 receptor (present as two isoforms: TP alpha and TP beta) is a GPCR
      displaying diverse pharmacological effects. As seen for many other GPCRs, TP beta
      is regulated by agonist-induced internalization. In the present study, we report
      the identification by yeast two-hybrid screening of Nm23-H2, a nucleoside
      diphosphate kinase, as a new interacting molecular partner with the C-terminal
      tail of TP beta. This interaction was confirmed in a cellular context when Nm23
      H2 was co-immunoprecipitated with TP beta in HEK293 cells, a process dependent on
      agonist stimulation of the receptor. We observed that agonist-induced
      internalization of TP beta was regulated by Nm23-H2 through modulation of Rac1
      signaling. Immunofluorescence microscopy in HEK293 cells revealed that Nm23-H2
      had a cytoplasmic and nuclear localization but was induced to translocate to the
      plasma membrane upon stimulation of TP beta to show extensive co-localization
      with the receptor. Our findings represent the first demonstration of an
      interaction of an Nm23 protein with a membrane receptor and constitute a novel
      molecular regulatory mechanism of GPCR endocytosis.

PMID- 14976203
TI  - Positive and negative allosteric modulators of the Ca2+-sensing receptor interact
      within overlapping but not identical binding sites in the transmembrane domain.
AB  - A three-dimensional model of the human extracellular Ca(2+)-sensing receptor
      (CaSR) has been used to identify specific residues implicated in the recognition
      of two negative allosteric CaSR modulators of different chemical structure, NPS
      2143 and Calhex 231. To demonstrate the involvement of these residues, we have
      analyzed dose-inhibition response curves for the effect of these calcilytics on
      Ca(2+)-induced [(3)H]inositol phosphate accumulation for the selected CaSR
      mutants transiently expressed in HEK293 cells. These mutants were further used
      for investigating the binding pocket of two chemically unrelated positive
      allosteric CaSR modulators, NPS R-568 and (R)-2-[1-(1-naphthyl)ethylaminomethyl]
      1H-indole (Calindol), a novel potent calcimimetic that stimulates (EC(50) = 0.31
      microM) increases in [(3)H]inositol phosphate levels elicited by activating the
      wild-type CaSR by 2 mM Ca(2+). Our data validate the involvement of Trp
      818(6.48), Phe-821(6.51), Glu-837(7.39), and Ile-841(7.43) located in
      transmembranes (TM) 6 and TM7, in the binding pocket for both calcimimetics and
      calcilytics, despite important differences observed between each family of
      compounds. The TMs involved in the recognition of both calcilytics include
      residues located in TM3 (Arg-680(3.28), Phe-684(3.32), and Phe-688(3.36)).
      However, our study indicates subtle differences between the binding of these two
      compounds. Importantly, the observation that some mutations that have no effect
      on calcimimetics recognition but which affect the binding of calcilytics in TM3
      and TM5, suggests that the binding pocket of positive and negative allosteric
      modulators is partially overlapping but not identical. Our CaSR model should
      facilitate the development of novel drugs of this important therapeutic target
      and the identification of the molecular determinants involved in the binding of
      allosteric modulators of class 3 G-protein-coupled receptors.

PMID- 14976204
TI  - Syndecan-2 regulates transforming growth factor-beta signaling.
AB  - Transforming growth factor-beta (TGF-beta) has multiple functions including
      increasing extracellular matrix deposition in fibrosis. It functions through a
      complex family of cell surface receptors that mediate downstream signaling. We
      report here that a transmembrane heparan sulfate proteoglycan, syndecan-2 (S2),
      can regulate TGF-beta signaling. S2 protein increased in the renal interstitium
      in diabetes and regulated TGF-beta-mediated increased matrix deposition in vitro.
      Transfection of renal papillary fibroblasts with S2 or a S2 construct that has a
      truncated cytoplasmic domain (S2DeltaS) promoted TGF-beta binding and S2 core
      protein ectodomain directly bound TGF-beta. Transfection with S2 increased the
      amounts of type I and type II TGF-beta receptors (TbetaRI and TbetaRII), whereas
      S2DeltaS was much less effective. In contrast, S2DeltaS dramatically increased
      the level of type III TGF-beta receptor (TbetaRIII), betaglycan, whereas S2
      resulted in a decrease. Syndecan-2 specifically co-immunoprecipitated with
      betaglycan but not with TbetaRI or TbetaRII. This is a novel mechanism of control
      of TGF-beta action that may be important in fibrosis.

PMID- 14976205
TI  - The coxsackievirus 2B protein suppresses apoptotic host cell responses by
      manipulating intracellular Ca2+ homeostasis.
AB  - Enteroviruses, small cytolytic RNA viruses, confer an antiapoptotic state to
      infected cells in order to suppress infection-limiting apoptotic host cell
      responses. This antiapoptotic state also lends protection against cell death
      induced by metabolic inhibitors like actinomycin D and cycloheximide. The
      identity of the viral antiapoptotic protein and the underlying mechanism are
      unknown. Here, we provide evidence that the coxsackievirus 2B protein modulates
      apoptosis by manipulating intracellular Ca(2+) homeostasis. Using fluorescent
      Ca(2+) indicators and organelle-targeted aequorins, we demonstrate that ectopic
      expression of 2B in HeLa cells decreases the Ca(2+) content of both the
      endoplasmic reticulum and the Golgi, resulting in down-regulation of Ca(2+)
      signaling between these stores and the mitochondria, and increases the influx of
      extracellular Ca(2+). In our studies of the physiological importance of the 2B
      induced alterations in Ca(2+) signaling, we found that the expression of 2B
      suppressed caspase activation and apoptotic cell death induced by various
      stimuli, including actinomycin D and cycloheximide. Mutants of 2B that were
      defective in reducing the Ca(2+) content of the stores failed to suppress
      apoptosis. These data implicate a functional role of the perturbation of
      intracellular Ca(2+) compartmentalization in the enteroviral strategy to suppress
      intrinsic apoptotic host cell responses. The putative down-regulation of an
      endoplasmic reticulum-dependent apoptotic pathway is discussed.

PMID- 14976206
TI  - NMR solution structures of delta-conotoxin EVIA from Conus ermineus that
      selectively acts on vertebrate neuronal Na+ channels.
AB  - Delta-conotoxin EVIA, from Conus ermineus, is a 32-residue polypeptide cross
      linked by three disulfide bonds forming a four-loop framework. delta-Conotoxin
      EVIA is the first conotoxin known to inhibit sodium channel inactivation in
      neuronal membranes from amphibians and mammals (subtypes rNa(v)1.2a, rNa(v)1.3,
      and rNa(v)1.6), without affecting rat skeletal muscle (subtype rNa(v)1.4) and
      human cardiac muscle (subtype hNa(v)1.5) sodium channel (Barbier, J., Lamthanh,
      H., Le Gall, F., Favreau, P., Benoit, E., Chen, H., Gilles, N., Ilan, N.,
      Heinemann, S. F., Gordon, D., Menez, A., and Molgo, J. (2004) J. Biol. Chem. 279,
      4680-4685). Its structure was solved by NMR and is characterized by a 1:1
      cis/trans isomerism of the Leu(12)-Pro(13) peptide bond in slow exchange on the
      NMR time scale. The structure of both cis and trans isomers could be calculated
      separately. The isomerism occurs within a specific long disordered loop 2,
      including residues 11-19. These contribute to an important hydrophobic patch on
      the surface of the toxin. The rest of the structure matches the "inhibitor
      cystine-knot motif" of conotoxins from the "O superfamily" with a high structural
      order. To probe a possible functional role of the Leu(12)-Pro(13) cis/trans
      isomerism, a Pro(13) --> Ala delta-conotoxin EVIA was synthesized and shown to
      exist only as a trans isomer. P13A delta-conotoxin EVIA was estimated only two
      times less active than the wild-type EVIA in binding competition to rat brain
      synaptosomes and when injected intracerebroventricularly into mice.

PMID- 14976207
TI  - A predicted amphipathic helix mediates plasma membrane localization of GRK5.
AB  - G protein-coupled receptor kinases (GRKs) specifically phosphorylate agonist
      occupied G protein-coupled receptors at the inner surface of the plasma membrane
      (PM), leading to receptor desensitization. GRKs utilize a variety of mechanisms
      to bind tightly, and sometimes reversibly, to cellular membranes. Previous
      studies demonstrated the presence of a membrane binding domain in the C terminus
      of GRK5. Here we define a mechanism by which this short C-terminal stretch of
      amino acids of GRK5 mediates PM localization. Secondary structure predictions
      suggest that a region contained within amino acids 546-565 of GRK5 forms an
      amphipathic helix, with the key features of the predicted helix being a
      hydrophobic patch of amino acids on one face of the helix, hydrophilic amino
      acids on the opposite face, and a number of basic amino acids surrounding the
      hydrophobic patch. We show that amino acids 546-565 of GRK5 are sufficient to
      target the cytoplasmic green fluorescent protein (GFP) to the PM, and the
      hydrophobic amino acids are necessary for PM targeting of GFP-546-565. Moreover,
      full-length GRK5-GFP is localized to the PM, but mutation of the hydrophobic
      patch or the surrounding basic amino acids prevents PM localization of GRK5-GFP.
      Last, we show that mutation of the hydrophobic residues severely diminishes
      phospholipid-dependent autophosphorylation of GRK5 and phosphorylation of
      membrane-bound rhodopsin by GRK5. The findings in this report thus suggest the
      presence of a membrane binding motif in GRK5 and define the importance of a group
      of hydrophobic amino acids within this motif in mediating its PM localization.

PMID- 14976208
TI  - Regulated internalization and phosphorylation of the native norepinephrine
      transporter in response to phorbol esters. Evidence for localization in lipid
      rafts and lipid raft-mediated internalization.
AB  - The effects of norepinephrine in the brain and periphery are terminated primarily
      by active reuptake of the catecholamine via cocaine- and amphetamine-sensitive
      norepinephrine transporters (NETs). Activation of protein kinase C (PKC) down
      regulates NET by sequestering it from the plasma membrane, although the
      underlying mechanism is not yet known. Previously, we showed robust expression of
      endogenous NETs in rat placental trophoblasts (Jayanthi, L. D., Vargas, G., and
      DeFelice, L. J. (2002) Br. J. Pharmacol. 135, 1927-1934). Here we report a
      significant reduction in native NET function and surface expression in these
      cells following phorbol ester (beta-PMA) treatment. The beta-PMA-mediated down
      regulation of NET occurs by a rapid sequestration of NETs from the plasma
      membrane and is calcium-independent. Reversible biotinylation experiments
      revealed a significant enhancement of NET endocytosis following beta-PMA
      treatment. Chemical treatments and expression of dominant negative mutants of
      dynamin 1 and 2 failed to prevent the beta-PMA effect, suggesting a clathrin
      independent pathway. In contrast, treatment with the cholesterol-disrupting agent
      filipin, which blocks caveolae/lipid raft-mediated internalization, completely
      blocked the beta-PMA-mediated NET sequestration. Discontinuous sucrose density
      gradient centrifugation revealed NET in the lipid raft fractions. Following beta
      PMA treatment, there was reduced NET levels in the lipid raft fractions
      suggesting that cholesterol-rich lipid rafts mediate PKC-triggered NET
      internalization. Metabolic labeling and immunoprecipitation studies revealed that
      NET phosphorylation is stimulated severalfold by PKC activation and protein
      phosphatase 1/2A inhibition. Together, these findings demonstrate for the first
      time that in trophoblasts (i) PKC activation regulates NET function and surface
      expression by an enhanced internalization process that is lipid raft-mediated and
      (ii) PKC and protein phosphatase(s) modulation regulates NET phosphorylation.

PMID- 14976209
TI  - Involvement of UBE1L in ISG15 conjugation during retinoid-induced differentiation
      of acute promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) cases expressing the t(15,17) product,
      promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARalpha), have
      clinical remissions through leukemic cell differentiation after all-trans
      retinoic acid (RA) treatment. This differentiation therapy propelled interest in
      uncovering molecular mechanisms for RA-dependent APL differentiation. We
      previously identified the ubiquitin-activating enzyme-E1-like protein (UBE1L) as
      an RA-regulated target gene in APL that triggers PML/RARalpha degradation and
      apoptosis. This study reports that conjugation of the ubiquitin-like species,
      interferon-stimulated gene, 15-kDa protein (ISG15), also occurs during RA-induced
      APL differentiation. Knock-down of UBE1L expression inhibited this conjugation.
      RA treatment of APL and other RA-responsive leukemic cells induced expression of
      UBE1L and ISG15 as well as intracellular ISG15 conjugates. Notably, ISG15
      conjugation did not occur in RA-resistant NB4-R1 APL cells. Induction of UBE1L
      and ISG15 along with ISG15 conjugation in RA-sensitive NB4-S1 APL cells were
      detected following treatment with specific retinoids and type I interferon (IFN).
      UBE1L and ISG15 mRNAs were co-expressed in normal human tissues that were
      examined. In contrast, UBE1L mRNA expression was markedly repressed in several
      cancer cell lines. A physical association was found between UBE1L and ISG15 in
      vivo. This required the conserved diglycine motif in the carboxyl terminus of
      ISG15. Targeting UBE1L expression with small inhibitory RNA or small hairpin RNA
      inhibited IFN and RA-induced ISG15 conjugation. Formation of ISG15 conjugates
      through induction of an activating enzyme represents a novel pharmacologic
      mechanism for regulation of this ubiquitin-related species. Taken together, the
      observed rela tionship between expression of UBE1L and ISG15, their physical
      association and coordinate regulation, and induced ISG15 conjugation during
      leukemic cell differentiation implicate an important role for these proteins in
      retinoid response.

PMID- 14976210
TI  - The Bacillus subtilis response regulator Spo0A stimulates sigmaA-dependent
      transcription prior to the major energetic barrier.
AB  - At the spoIIG promoter phosphorylated Spo0A (Spo0A approximately P) binds 0A
      boxes overlapping the -35 element, interacting with RNA polymerase to facilitate
      open complex formation. We have compared in vitro transcription from a series of
      heteroduplex templates containing denatured regions within the promoters.
      Transcription from heteroduplex templates with 12, 8, or 6 base pairs denatured
      was independent of Spo0A approximately P, but heteroduplexes with 4 or 2 base
      pairs denatured required Spo0A approximately P for maximal levels of
      transcription. Investigation of the thermal dependence of transcription suggested
      that strand separation was the primary thermodynamic barrier to transcription
      initiation but indicated that Spo0A approximately P does not reduce this
      energetic barrier. Kinetic assays revealed that Spo0A approximately P stimulated
      both the rate of formation of initiated complexes as well as increasing the
      number of complexes capable of initiating transcription. These results imply that
      Spo0A approximately P stimulates transcription at least in part by stabilizing
      the RNA polymerase-spoIIG complex until contacts between RNA polymerase and the 
      10 element induce strand separation.

PMID- 14976211
TI  - Mutational analysis of different regions in the coxsackievirus 2B protein:
      requirements for homo-multimerization, membrane permeabilization, subcellular
      localization, and virus replication.
AB  - The coxsackievirus 2B protein is a small hydrophobic protein (99 amino acids)
      that increases host cell membrane permeability, possibly by forming homo
      multimers that build membrane-integral pores. Previously, we defined the
      functional role of the two hydrophobic regions HR1 and HR2. Here, we investigated
      the importance of regions outside HR1 and HR2 for multimerization, increasing
      membrane permeability, subcellular localization, and virus replication through
      analysis of linker insertion and substitution mutants. From these studies, the
      following conclusions could be drawn. (i) The hydrophilic region ((58)RNHDD(62))
      between HR1 and HR2 is critical for multimerization and increasing membrane
      permeability. Substitution analysis of Asn(61) and Asn(62) demonstrated the
      preference for short polar side chains (Asp, Asn), residues that are often
      present in turns, over long polar side chains (Glu, Gln). This finding supports
      the idea that the hydrophilic region is involved in pore formation by
      facilitating a turn between HR1 and HR2 to reverse chain direction. (ii) Studies
      undertaken to define the downstream boundary of HR2 demonstrated that the
      aromatic residues Trp(80) and Trp(82), but not the positively charged residues
      Arg(81), Lys(84), and Lys(86) are important for increasing membrane permeability.
      (iii) The N terminus is not required for multimerization but does contribute to
      the membrane-active character of 2B. (iv) The subcellular localization of 2B does
      not rely on regions outside HR1 and HR2 and does not require multimerization. (v)
      Virus replication requires both the membrane-active character and an additional
      function of 2B that is not connected to this activity.

PMID- 14976212
TI  - Bacterial penetration of bladder epithelium through lipid rafts.
AB  - Type 1 fimbriated Escherichia coli represents the most common human uropathogen,
      owing much of its virulence to invasion of the uroepithelium, which is highly
      impermeable due to the preponderance of uroplakins and highly ordered lipid
      components. We sought to elucidate the molecular basis for E. coli invasion of
      the bladder epithelium by employing human 5637 bladder epithelial cells, and we
      found the following: (i) intracellular E. coli associated with caveolae and lipid
      raft components; (ii) RNA(i) reduction of caveolin-1 expression inhibited
      bacterial invasion; (iii) a signaling molecule required for E. coli invasion was
      located in lipid rafts and physically associated with caveolin-1; (iv) bacterial
      invasion was inhibited by lipid raft disrupting/usurping agents. In the mouse
      bladder, the E. coli type 1 fimbrial receptor, uroplakin Ia, was located in lipid
      rafts, and lipid raft disruptors inhibited E. coli invasion. Cumulatively, E.
      coli uroepithelial invasion occurs through lipid rafts, which, paradoxically,
      contribute to bladder impermeability.

PMID- 14976213
TI  - Biochemical characterization of the high affinity binding between the glycine
      receptor and gephyrin.
AB  - Gephyrin is an essential and instructive molecule for the formation of inhibitory
      synapses. Gephyrin binds directly to the large cytoplasmic loop located between
      transmembrane helices three and four of the beta-subunit of the glycine receptor
      and to microtubules, thus promoting glycine receptor (GlyR) anchoring to the
      cytoskeleton and clustering in the postsynaptic membrane. Besides its structural
      role, gephyrin is involved in the biosynthesis of the molybdenum cofactor that is
      essential for all molybdenum-dependent enzymes in mammals. Gephyrin can be
      divided into an N-terminal trimeric G domain and a C-terminal E domain, which are
      connected by a central linker region. Here we have studied the in vitro
      interaction of gephyrin and its domains with the large cytoplasmic loop of the
      GlyR beta-sub-unit (GlyRbeta-loop). Binding of gephyrin to the GlyR is
      exclusively mediated by the E domain, and the binding site was mapped to one of
      its sub-domains (residues 496-654). By using isothermal titration calorimetry, a
      high affinity (K(d) = 0.2-0.4 microm) and low affinity (K(d) = 11-30 microm)
      binding site for the GlyRbeta-loop was found on holo-gephyrin and the E domain,
      respectively, with a binding stoichiometry of two GlyRbeta-loops per E domain in
      both cases. Binding of the GlyRbeta-loop does not change the oligomeric state of
      either full-length gephyrin or the isolated E domain.

PMID- 14976214
TI  - Furcatin hydrolase from Viburnum furcatum Blume is a novel disaccharide-specific
      acuminosidase in glycosyl hydrolase family 1.
AB  - Furcatin hydrolase (FH) is a unique disaccharide-specific acuminosidase, which
      hydrolyzes furcatin (p-allylphenyl 6-O-beta-D-apiofuranosyl-beta-D
      glucopyranoside (acuminoside)) into p-allylphenol and the disaccharide acuminose.
      We have isolated a cDNA coding for FH from Viburnum furcatum leaves. The open
      reading frame in the cDNA encoded a 538-amino acid polypeptide including a
      putative chloroplast transit peptide. The deduced protein showed 64% identity
      with tea leaf beta-primeverosidase, which is another disaccharide glycosidase
      specific to beta-primeverosides (6-O-beta-D-xylopyranosyl-beta-D
      glucopyranosides). The deduced FH also shared greater than 50% identity with
      various plant beta-glucosidases in glycosyl hydrolase family 1. The recombinant
      FH expressed in Escherichia coli exhibited the highest level of activity toward
      furcatin with a Km value of 2.2 mm and specifically hydrolyzed the beta
      glycosidic bond between p-allylphenol and acuminose, confirming FH as a
      disaccharide glycosidase. The FH also hydrolyzed beta-primeverosides and beta
      vicianoside (6-O-alpha-L-arabinopyranosyl-beta-D-glucopyranoside) but poorly
      hydrolyzed beta-gentiobiosides (6-O-beta-D-glucopyranosyl-beta-d
      glucopyranosides), indicating high substrate specificity for the disaccharide
      glycone moiety. The FH exhibited activity toward p-allylphenyl beta-D
      glucopyranoside containing the same aglycone as furcatin but little activity
      toward the other beta-D-glucopyranosides. Stereochemical analysis using 1H NMR
      spectroscopy revealed that FH is a retaining glycosidase. The subcellular
      localization of FH was analyzed using green fluorescent protein fused with the
      putative N-terminal signal peptide, indicating that FH is localized to the
      chloroplast. Phylogenetic analysis of plant beta-glucosidases revealed that FH
      clusters with beta-primeverosidase, and this suggests that the disaccharide
      glycosidases will form a new subfamily in glycosyl hydrolase family 1.

PMID- 14976215
TI  - Ligand-regulated chimeric receptor approach reveals distinctive subcellular
      localization and signaling properties of the Toll-like receptors.
AB  - Toll-like receptors (TLRs) are sensors for the detection of invading infectious
      agents and can initiate innate immune responses. Because the innate immune system
      induces an appropriate defense against different pathogens, different TLR
      signaling domains may have unique properties that are responsible for eliciting
      distinctive responses to different types of pathogens. To test this hypothesis,
      we created ligand-regulated TLR chimeric receptors composed of the extracellular
      region of TLR4 and the transmembrane and cytoplasmic regions of other TLRs and
      expressed these chimeras in macrophages lacking endogenous TLR4. Interestingly,
      the chimeras between TLR4 and either TLR3, TLR7, or TLR9 were localized
      completely intracellularly whereas other chimeras were expressed on the cell
      surface. Lipopolysaccharide (LPS), a ligand for these chimeras, induced the
      activation of nuclear factor kappa B and mitogen-activated protein kinases and
      the subsequent production of pro-inflammatory cytokines in macrophages expressing
      TLR4, TLR4/TLR5, or TLR4/TLR8 chimeras but not in macrophages expressing
      TLR4/TLR1, TLR4/TLR2, or TLR4/TLR6 chimeras. Co-expression of unresponsive
      chimeras in some combinations (chimeras with TLR1+TLR2 or TLR2+TLR6 but not
      TLR1+TLR6) resulted in LPS responsiveness, indicating functional complementarity.
      Furthermore, the pair of TLR2+TLR6 chimera required approximately 10-fold less
      LPS to induce the same responses compared with the TLR1+TLR2 pair. Finally, LPS
      induced effective interferon-beta production and subsequent Stat1 phosphorylation
      in macrophages expressing full-length TLR4 but not other cell surface TLR
      chimeras. These results suggest that the functions of TLRs are diversified not
      only in their extracellular regions for ligand recognition but also in their
      transmembrane and cytoplasmic regions for subcellular localization and signaling
      properties.

PMID- 14976216
TI  - A conserved Val to Ile switch near the heme pocket of animal and bacterial nitric
      oxide synthases helps determine their distinct catalytic profiles.
AB  - Nitric oxide (NO) release from nitric oxide synthases (NOSs) is largely dependent
      on the dissociation of an enzyme ferric heme-NO product complex (Fe(III)NO).
      Although the NOS-like protein from Bacillus subtilis (bsNOS) generates Fe(III)NO
      from the reaction intermediate N-hydroxy-l-arginine (NOHA), its NO dissociation
      is about 20-fold slower than in mammalian NOSs. Crystal structures suggest that a
      conserved Val to Ile switch near the heme pocket of bsNOS might determine its
      kinetic profile. To test this we generated complementary mutations in the mouse
      inducible NOS oxygenase domain (iNOSoxy, V346I) and in bsNOS (I224V) and
      characterized the kinetics and extent of their NO synthesis from NOHA and their
      NO-binding kinetics. The mutations did not greatly alter binding of Arg, (6R)
      tetrahydrobiopterin, or alter the electronic properties of the heme or various
      heme-ligand complexes. Stopped-flow spectroscopy was used to study heme
      transitions during single turnover NOHA reactions. I224V bsNOS displayed three
      heme transitions involving four species as typically occurs in wild-type NOS, the
      beginning ferrous enzyme, a ferrous-dioxy (Fe(II)O(2)) intermediate, Fe(III)NO,
      and an ending ferric enzyme. The rate of each transition was increased relative
      to wild-type bsNOS, with Fe(III)NO dissociation being 3.6 times faster. In V346I
      iNOSoxy we consecutively observed the beginning ferrous, Fe(II)O(2), a mixture of
      Fe(III)NO and ferric heme species, and ending ferric enzyme. The rate of each
      transition was decreased relative to wild-type iNOSoxy, with the Fe(III)NO
      dissociation being 3 times slower. An independent measure of NO binding kinetics
      confirmed that V346I iNOSoxy has slower NO binding and dissociation than wild
      type. Citrulline production by both mutants was only slightly lower than wild
      type enzymes, indicating good coupling. Our data suggest that a greater shielding
      of the heme pocket caused by the Val/Ile switch slows down NO synthesis and NO
      release in NOS, and thus identifies a structural basis for regulating these
      kinetic variables.

PMID- 14976217
TI  - Clathrin-mediated endocytosis of Na+,K+-ATPase in response to parathyroid hormone
      requires ERK-dependent phosphorylation of Ser-11 within the alpha1-subunit.
AB  - Parathyroid hormone (PTH) inhibits Na(+),K(+)-ATPase activity through protein
      kinase C- (PKC) and extracellular signal-regulated kinase- (ERK) dependent
      pathways and increases serine phosphorylation of the alpha(1)-subunit. To
      determine whether specific serine phosphorylation sites within the Na(+),K(+)
      ATPase alpha(1)-subunit are involved in the Na(+),K(+)-ATPase responses to PTH,
      we examined the effect of PTH in opossum kidney cells stably transfected with
      wild type rat Na(+),K(+)-ATPase alpha(1)-subunit (WT), serine 11 to alanine
      mutant alpha(1)-subunit (S11A), or serine 18 to alanine mutant alpha(1)-subunit
      (S18A). PTH increased phosphorylation and endocytosis of the Na(+),K(+)-ATPase
      alpha(1)-subunit into clathrin-coated vesicles in cells transfected with WT and
      S18A rat Na(+),K(+)-ATPase alpha(1)-subunits. PTH did not increase the level of
      phosphorylation or stimulate translocation of Na(+),K(+)-ATPase alpha(1)-subunits
      into clathrin-coated vesicles in cells transfected with the S11A mutant. PTH
      inhibited ouabain-sensitive (86)Rb uptake and Na(+),K(+)-ATPase activity (ouabain
      sensitive ATP hydrolysis) in WT- and S18A-transfected opossum kidney cells but
      not in S11A-transfected cells. Pretreatment of the cells with the PKC inhibitors
      and ERK inhibitor blocked PTH inhibition of (86)Rb uptake, Na(+),K(+)-ATPase
      activity, alpha(1)-subunit phosphorylation, and endocytosis in WT and S18A cells.
      Consistent with the notion that ERK phosphorylates Na(+),K(+)-ATPase alpha(1)
      subunit, ERK was shown to be capable of causing phosphorylation of Na(+),K(+)
      ATPase alpha(1)-subunit immunoprecipitated from WT and S18A but not from S11A
      transfected cells. These results suggest that PTH regulates Na(+),K(+)-ATPase by
      PKC and ERK-dependent alpha(1)-subunit phosphorylation and that the
      phosphorylation requires the expression of a serine at the 11 position of the
      Na(+),K(+)-ATPase alpha(1)-subunit.

PMID- 14976218
TI  - In vivo chromatin remodeling events leading to inflammatory gene transcription
      under diabetic conditions.
AB  - The transcription factor NF-kappaB (NF-kappaB) plays a pivotal role in regulating
      inflammatory gene expression. Its effects are optimized by various coactivators
      including histone acetyltransferases (HATs) such as CBP/p300 and p/CAF. Evidence
      shows that high glucose (HG) conditions mimicking diabetes can activate the
      transcription of NF-kappaB-regulated inflammatory genes. However, the underlying
      in vivo transcription and nuclear chromatin remodeling events are unknown. We
      therefore carried out chromatin immunoprecipitation (ChIP) assays in monocytes to
      identify 1) chromatin factors bound to the promoters of tumor necrosis factor
      alpha (TNF-alpha) and related NF-kappaB-regulated genes under HG or diabetic
      conditions, 2) specific lysine (Lys (K)) residues on histone H3 (HH3) and HH4
      acetylated in this process. HG treatment of THP-1 monocytes increased the
      transcriptional activity of NF-kappaB p65, which was augmented by CBP/p300 and
      p/CAF. ChIP assays showed that HG increased the recruitment of NF-kappaB p65,
      CPB, and p/CAF to the TNF-alpha and COX-2 promoters. Interestingly, ChIP assays
      also demonstrated concomitant acetylation of HH3 at Lys(9) and Lys(14), and HH4
      at Lys(5), Lys(8), and Lys(12) at the TNF-alpha and COX-2 promoters.
      Overexpression of histone deacetylase (HDAC) isoforms inhibited p65-mediated TNF
      alpha transcription. In contrast, a HDAC inhibitor stimulated gene transcription
      and histone acetylation. Finally, we demonstrated increased HH3 acetylation at
      TNF-alpha and COX-2 promoters in human blood monocytes from type 1 and type 2
      diabetic subjects relative to nondiabetic. These results show for the first time
      that diabetic conditions can increase in vivo recruitment of NF-kappaB and HATs,
      as well as histone acetylation at the promoters of inflammatory genes, leading to
      chromatin remodeling and transcription.

PMID- 14976219
TI  - In vivo interactions of the Acanthamoeba TBP gene promoter.
AB  - Transcription of the TATA box binding protein (TBP) gene in Acanthamoeba
      castellanii is regulated by TATA box binding protein promoter binding factor
      (TPBF), which binds to an upstream TBP promoter element to stimulate
      transcription, and to a TATA proximal element, where it represses transcription.
      In order to extend these observations to the in vivo chromatin context, the TBP
      gene was examined by in situ footprinting and chromatin immunoprecipitation
      (ChIP). Acanthamoeba DNA is nucleosomal with a repeat of approximately 160 bp,
      and an intranucleosomal DNA periodicity of 10.5 bp. The TBP gene comprises a 220
      bp micrococcal nuclease hypersensitive site corresponding to the promoter
      regulatory elements previously identified, flanked by protected regions of a size
      consistent with the presence of nucleosomes. ChIP data indicated that TPBF is
      associated with the TBP, TPBF and MIL gene promoters, but not to the CSP21,
      MIIHC, 5SrRNA or 39SrRNA promoters, or to the MIL gene C-terminal region. Binding
      by TPBF to the TPBF and MIL gene promoters was confirmed by in vitro assays.
      These results validate the in vitro model for TBP gene regulation and further
      suggest that TPBF may be autoregulated and may participate in the regulation of
      the MIL gene.

PMID- 14976220
TI  - Roles of AUF1 isoforms, HuR and BRF1 in ARE-dependent mRNA turnover studied by
      RNA interference.
AB  - HT1080 cells stably expressing green fluorescent protein (GFP) linked to a 3'
      terminal AU-rich element (ARE) proved to be a convenient system to study the
      dynamics of mRNA stability, as changes in mRNA levels are reflected in increased
      or decreased fluorescence intensity. This study examined whether mRNA stability
      can be regulated by small interfering RNAs (siRNAs) targeted to AU-binding
      proteins (AUBPs), which in turn should reveal their intrinsic role as stabilizers
      or destabilizers of ARE-mRNAs. Indeed, siRNAs targeting HuR or BRF1 decreased or
      increased fluorescence, respectively. This effect was abolished if cells were
      treated with both siRNAs, thus indicating antagonistic control of ARE-mRNA
      stability. Unexpectedly, downregulation of all four AUF1 isoforms by targeting
      common exons did not affect fluorescence whereas selective downregulation of
      p40AUF1/p45AUF1 strongly increased fluorescence by stabilizing the GFP-ARE
      reporter mRNA. This observation was fully confirmed by the finding that only
      selective reduction of p40AUF1/p45AUF1 induced the production of GM-CSF, an
      endogenous target of AUF1. These data suggest that the relative levels of
      individual isoforms, rather than the absolute amount of AUF1, determine the net
      mRNA stability of ARE-containing transcripts, consistent with the differing ARE
      binding capacities of the isoforms.

PMID- 14976221
TI  - Leptin increases hepatic insulin sensitivity and protein tyrosine phosphatase 1B
      expression.
AB  - Leptin has been shown to improve insulin sensitivity and glucose metabolism in
      obese diabetic ob/ob mice, yet the mechanisms remain poorly defined. We found
      that 2 d of leptin treatment improved fasting but not postprandial glucose
      homeostasis, suggesting enhanced hepatic insulin sensitivity. Consistent with
      this hypothesis, leptin improved in vivo insulin receptor (IR) activation in
      liver, but not in skeletal muscle or fat. To explore the cellular mechanism by
      which leptin up-regulates hepatic IR activation, we examined the expression of
      the protein tyrosine phosphatase PTP1B, recently implicated as an important
      negative regulator of insulin signaling. Unexpectedly, liver PTP1B protein
      abundance was increased by leptin to levels similar to lean controls, whereas
      levels in muscle and fat remained unchanged. The ability of leptin to augment
      liver IR activation and PTP1B expression was also observed in vitro in human
      hepatoma cells (HepG2). However, overexpression of PTP1B in HepG2 cells led to
      diminished insulin-induced IR phosphorylation, supporting the role of PTP1B as a
      negative regulator of IR activation in hepatocytes. Collectively, our results
      suggest that leptin acutely improves hepatic insulin sensitivity in vivo with
      concomitant increases in PTP1B expression possibly serving to counterregulate
      insulin action and to maintain insulin signaling in proper balance.

PMID- 14976222
TI  - Partitioning-defective protein 6 regulates insulin-dependent glycogen synthesis
      via atypical protein kinase C.
AB  - The atypical isoforms of protein kinase C (aPKCs) play an important role in
      insulin signaling and are involved in insulin-stimulated glucose uptake in
      different cell systems. On the other hand, aPKCs also are able to negatively
      regulate important proteins for insulin signaling, like phosphatidylinositol 3
      kinase and protein kinase B/Akt. To find aPKC-interacting proteins that may
      promote positive or negative activities of aPKCs, a yeast two-hybrid screen was
      performed. Partitioning-defective protein 6 (Par6) was detected in human cDNA
      libraries of different adult insulin-sensitive tissues. Although Par6 is known as
      an aPKC-interacting protein during development, no role for Par6 in insulin
      signaling has been reported so far. We therefore studied the effects of Par6
      overexpression in C2C12 murine myoblasts. In these cells, Par6 associated
      constitutively with endogenous aPKCs, and the expression level as well as the
      activity of aPKCs were increased. Insulin-dependent association of the p85
      subunit of phosphatidylinositol 3-kinase with insulin receptor substrate 1 was
      hampered and the phosphorylation of Akt/glycogen synthase kinase-3alpha/beta was
      significantly impaired after stimulation with insulin or with platelet-derived
      growth factor. Consequently, insulin-dependent glycogen synthesis was down
      regulated (1.44 vs. 2.24 fold, P < 0.01). We therefore suggest that Par6 acts as
      a negative regulator of the insulin signal.

PMID- 14976223
TI  - Uterine Msx-1 and Wnt4 signaling becomes aberrant in mice with the loss of
      leukemia inhibitory factor or Hoxa-10: evidence for a novel cytokine-homeobox-Wnt
      signaling in implantation.
AB  - Successful implantation absolutely depends on the reciprocal interaction between
      the implantation-competent blastocyst and the receptive uterus. Expression and
      gene targeting studies have shown that leukemia inhibitory factor (LIF), a
      cytokine of the IL-6 family, and Hoxa-10, an abdominalB-like homeobox gene, are
      crucial to implantation and decidualization in mice. Using these mutant mice, we
      sought to determine the importance of Msx-1 (another homeobox gene formerly known
      as Hox-7.1) and of Wnt4 (a ligand of the Wnt family) signaling in implantation
      because of their reported functions during development. We observed that Msx-1,
      Wnt4, and a Wnt antagonist sFRP4 are differentially expressed in the mouse uterus
      during the periimplantation period, suggesting their role in implantation. In
      addition, we observed an aberrant uterine expression of Msx-1 and sFRP4 in Lif
      mutant mice, and of Wnt4 and sFRP4 in Hoxa-10 mutant mice, further reinforcing
      the importance of these signaling pathways in implantation. Collectively, the
      present results provide evidence for a novel cytokine-homeotic-Wnt signaling
      network in implantation.

PMID- 14976224
TI  - Real-time detection of interactions between the human oxytocin receptor and G
      protein-coupled receptor kinase-2.
AB  - Although the oxytocin receptor (OTR) mediates many important functions including
      uterine contractions, milk ejection, and maternal behavior, the mechanisms
      controlling agonist-induced OTR desensitization have remained unclear, and
      attempts to demonstrate involvement of a G protein-coupled receptor kinase (GRK)
      have so far failed. Using the OTR as a model, we demonstrate here directly for
      the first time the dynamics of agonist-induced interactions of a GRK with a G
      protein-coupled receptor in real time, using time-resolved bioluminescence
      resonance energy transfer. GRK2/receptor interactions started within 4 sec,
      peaked at 10 sec, and decreased to less than 40% within 8 min. By contrast, beta
      arrestin/OTR interactions initiated only at 10 sec, reached plateau levels at 120
      sec, but remained stable with little decrease thereafter. Physical GRK2/OTR
      association was further demonstrated by coimmunoprecipitation of endogenous GRK2
      with activated OTR. In COS-7 cells, which express low levels of GRK2 and beta
      arrestin, overexpression of GRK2 and beta-arrestin increased receptor
      phosphorylation, desensitization, and internalization to the high levels observed
      in human embryonic kidney 293 cells. By contrast, specific inhibition of
      endogenous GRK2 by dominant-negative mutants robustly inhibited OTR
      phosphorylation and internalization as well as arrestin/OTR interactions. These
      data characterize the temporal and causal relationship of GRK-2/OTR and beta
      arrestin/OTR interactions and establish GRK/OTR interaction as a prerequisite for
      beta-arrestin-mediated OTR desensitization.

PMID- 14976225
TI  - The Wnt antagonist secreted frizzled-related protein-1 is a negative regulator of
      trabecular bone formation in adult mice.
AB  - Previous studies have associated activation of canonical Wnt signaling in
      osteoblasts with elevated bone formation. Here we report that deletion of the
      murine Wnt antagonist, secreted frizzled-related protein (sFRP)-1, prolongs and
      enhances trabecular bone accrual in adult animals. sFRP-1 mRNA was expressed in
      bones and other tissues of +/+ mice but was not observed in -/- animals. Despite
      its broad tissue distribution, ablation of sFRP-1 did not affect blood and urine
      chemistries, most nonskeletal organs, or cortical bone. However, sFRP-1-/- mice
      exhibited increased trabecular bone mineral density, volume, and mineral
      apposition rate when compared with +/+ controls. The heightened trabecular bone
      mass of sFRP-1-/- mice was observed in adult animals between the ages of 13-52
      wk, occurred in multiple skeletal sites, and was seen in both sexes.
      Mechanistically, loss of sFRP-1 reduced osteoblast and osteocyte apoptosis in
      vivo. In addition, deletion of sFRP-1 inhibited osteoblast lineage cell apoptosis
      while enhancing the proliferation and differentiation of these cells in vitro.
      Ablation of sFRP-1 also increased osteoclastogenesis in vitro, although changes
      in bone resorption were not observed in intact animals in vivo. Our findings
      demonstrate that deletion of sFRP-1 preferentially activates Wnt signaling in
      osteoblasts, leading to enhanced trabecular bone formation in adults.

PMID- 14976226
TI  - Correlation between in vitro peptide binding profiles and cellular activities for
      estrogen receptor-modulating compounds.
AB  - Numerous biochemical and structural studies have shown that the conformation of
      the estrogen receptor alpha (ERalpha) can be influenced by ligand binding. In
      turn, the conformational state of ERalpha affects the ability of the receptor to
      interact with a wide variety of protein accessory factors. To globally
      investigate ligand-based cofactor recruitment activities of ERalpha, we have
      applied a flow cytometric multiplexed binding assay to determine the simultaneous
      binding of ERalpha to over 50 different peptides derived from both known cofactor
      proteins and random peptide phage display. Using over 400 ERalpha-binding
      compounds, we have observed that the multiplexed in vitro peptide-binding
      profiles are distinct for a number of compounds and that these profiles can
      predict the effect that ERalpha ligands have on various cellular activities.
      These cell-based activities include transcriptional regulation at an estrogen
      response element, MCF-7 cell proliferation, and Ishikawa endometrial cell
      stimulation. The majority of the compound-induced diversity in the peptide
      profiling assay is provided by the unique phage display peptides. Importantly,
      some of these peptides show a sequence relationship with the corepressor motif,
      suggesting that peptides identified via phage display might represent natural
      binding partners of ERalpha. These in vitro:cellular correlations may in part
      explain tissue-specific activities of ERalpha-modulating compounds.

PMID- 14976227
TI  - Potent and metabolically stable agonists for protease-activated receptor-2:
      evaluation of activity in multiple assay systems in vitro and in vivo.
AB  - To develop potent and metabolically stable agonists for protease-activated
      receptor-2 (PAR-2), we prepared 2-furoylated (2f) derivatives of native PAR-2
      activating peptides, 2f-LIGKV-OH, 2f-LIGRL-OH, 2f-LIGKV-NH(2), and 2f-LIGRL
      NH(2), and systematically evaluated their activity in PAR-2-responsive cell lines
      and tissues. In both HCT-15 cells and NCTC2544 cells overexpressing PAR-2, all
      furoylated peptides increased cytosolic Ca(2+) levels with a greater potency than
      the corresponding native peptides, although a similar maximum response was
      recorded. The absolute potency of each peptide was greater in NCTC2544, possibly
      due to a higher level of receptor expression. Furthermore, the difference in
      potency between the 2-furoylated peptides and the native peptides was enhanced
      when evaluated in the rat superior mesenteric artery and further increased when
      measuring PAR-2-mediated salivation in ddY mice in vivo. The potency of 2f-LIGRL
      NH(2), the most powerful peptide, relative to SLIGKV-OH, was about 100 in the
      cultured cell Ca(2+) signaling assays, 517 in the vasorelaxation assay, and 1100
      in the salivation assay. Amastatin, an aminopeptidase inhibitor, augmented
      salivation caused by native peptides, but not furoylated peptides. The PAR-2
      activating peptides, including the furoylated derivatives, also produced
      salivation in the wild-type C57BL/6 mice, but not the PAR-2-deficient mice. Our
      data thus demonstrate that substitution of the N-terminal serine with a furoyl
      group in native PAR-2-activating peptides dramatically enhances the agonistic
      activity and decreases degradation by aminopeptidase, leading to development of
      2f-LIGRL-NH(2), the most potent peptide. Furthermore, the data from PAR-2
      deficient mice provide ultimate evidence for involvement of PAR-2 in salivation
      and the selective nature of the 2-furoylated peptides.

PMID- 14976228
TI  - Agonist-induced serotonin 2A receptor desensitization in the rat frontal cortex
      and hypothalamus.
AB  - This study examined the time course and possible mechanisms of agonist-induced
      desensitization of 5-hydroxytryptamine serotonin 2A receptors in the rat frontal
      cortex and hypothalamic paraventricular nucleus after 1, 4, and 7 days of
      treatment with (-)-1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane HCl [(-)-DOI] (1
      mg/kg i.p.), a selective 5-HT(2A/2C) receptor agonist. In the frontal cortex, 5
      HT-mediated phospholipase C (PLC) enzyme activity decreased by 24 to 30% after 4
      to 7 days of (-)-DOI treatment without any significant changes in the guanosine
      5'-3-O-(thio)triphosphate-mediated PLC enzyme activity. Additionally, treatment
      with (-)-DOI did not significantly change the levels of G(alpha11), regulator of
      G protein signaling (RGS)4, or RGS7 proteins in the frontal cortex, whereas
      G(alphaq) protein levels in the frontal cortex decreased (47%) only after 7 daily
      (-)-DOI injections. The functional status of 5-HT(2A) receptors in the
      hypothalamic paraventricular nucleus was examined using 5-HT(2A) receptor
      mediated increases in plasma hormone levels. Plasma adrenocorticotrophic hormone
      (ACTH) and oxytocin measurements showed that 5-HT(2A) receptor desensitization
      began after only 1 day of (-)-DOI treatment, and the desensitization continued to
      increase after 4 and 7 days of treatment (ACTH response decreased 64.2-67.7%;
      oxytocin response decreased 82.3-90.1%). There were no significant alterations in
      levels of G(alphaq) or G(alpha11) lamic paraventricular proteins in the
      hypothanucleus. In conclusion, these results suggest that chronically
      administered (-)-DOI induces desensitization of 5-HT(2A) receptors in vivo, via a
      reduction in the ability of 5-HT(2A) receptors to activate G proteins without
      consistently altering levels of G(alpha) proteins or RGS proteins.

PMID- 14976229
TI  - Role of alpha7 nicotinic acetylcholine receptors in the pressor response to
      intracerebroventricular injection of choline: blockade by amyloid peptide Abeta1
      42.
AB  - Systemic blood pressure and cardiac function have long been known to be under the
      control of central autonomic and hormonal pathways that, in part, use cholinergic
      neural systems. Recently choline, a precursor and product of acetylcholine
      metabolism, has been shown to serve as a selective endogenous agonist for the
      alpha7 subtype of the nicotinic acetylcholine receptor (alpha7nAChR). This
      receptor subtype mediates several responses to nicotine in animals, most notably,
      neuroprotection and enhanced cognition. The purpose of this study was to
      determine whether the cardiovascular changes induced by central injection of
      choline in rats also were mediated by alpha7nAChRs. Moreover, we sought to
      determine whether these cardiovascular changes to choline could be blocked by
      central pretreatment with amyloid beta peptide (1-42) (Abeta1-42), a neurotoxic
      component of cerebral amyloid that is known to bind with high affinity to
      alpha7nAChRs. Central, i.c.v. injection of choline (50, 100, or 150 microg)
      produced dose-dependent (10-15-min duration) pressor response of up to about 20
      mm Hg. The most consistent change in heart rate included a brief increase (up to
      40 beats/min) that lasted 2 to 3 min, followed by a prolonged decrease averaging
      50 beats/min that lasted up to 30 min. Pretreatment (i.c.v.) with the selective
      alpha7nAChR antagonists alpha-bungarotoxin and methyllycaconitine significantly
      inhibited the pressor and heart rate responses to subsequent injection of
      choline. Pretreatment with the non-alpha7-preferring antagonist dihydro-beta
      erythroidin was not effective. These findings suggested that the cardiovascular
      response to i.c.v. injection of choline was mediated at least in part through
      alpha7nAChRs. Pretreatment (30 min) with low doses (1-100 pmol) of amyloid
      peptide Abeta1-42 (but not with Abeta40-1) administered by the i.c.v. route
      significantly inhibited the choline-induced blood pressure increase as well as
      the choline-induced decrease in heart rate.

PMID- 14976230
TI  - 2-furoyl-LIGRLO-amide: a potent and selective proteinase-activated receptor 2
      agonist.
AB  - A peptide corresponding to a proteinase-activated receptor 2 (PAR(2))-activating
      peptide with an N-terminal furoyl group modification, 2-furoyl-LIGRLO-NH(2), was
      assessed for PAR(2)-dependent and -independent biological activities. 2-Furoyl
      LIGRLO-NH(2) was equally effective to and 10 to 25 times more potent than
      SLIGRLNH(2) for increasing intracellular calcium in cultured human and rat PAR(2)
      expressing cells, respectively. In bioassays of tissue PAR(2) activity, measured
      as arterial vasodilation and hyperpolarization, 2-furoyl-LIGRLO-NH(2) was 10 to
      300 times more potent than SLIGRL-NH(2). Unlike trans-cinnamoyl-LIGRLO-NH(2), 2
      furoyl-LI-GRLO-NH(2) did not cause a prominent non-PAR(2)-mediated contraction of
      murine femoral arteries. In conclusion, 2-furoyl-LI-GRLO-NH(2) represents the
      most potent and selective activator of PAR(2) in biological systems described to
      date.

PMID- 14976231
TI  - Bacterial volatiles induce systemic resistance in Arabidopsis.
AB  - Plant growth-promoting rhizobacteria, in association with plant roots, can
      trigger induced systemic resistance (ISR). Considering that low-molecular weight
      volatile hormone analogues such as methyl jasmonate and methyl salicylate can
      trigger defense responses in plants, we examined whether volatile organic
      compounds (VOCs) associated with rhizobacteria can initiate ISR. In Arabidopsis
      seedlings exposed to bacterial volatile blends from Bacillus subtilis GB03 and
      Bacillus amyloliquefaciens IN937a, disease severity by the bacterial pathogen
      Erwinia carotovora subsp. carotovora was significantly reduced compared with
      seedlings not exposed to bacterial volatiles before pathogen inoculation.
      Exposure to VOCs from rhizobacteria for as little as 4 d was sufficient to
      activate ISR in Arabidopsis seedlings. Chemical analysis of the bacterial
      volatile emissions revealed the release of a series of low-molecular weight
      hydrocarbons including the growth promoting VOC (2R,3R)-(-)-butanediol. Exogenous
      application of racemic mixture of (RR) and (SS) isomers of 2,3-butanediol was
      found to trigger ISR and transgenic lines of B. subtilis that emitted reduced
      levels of 2,3-butanediol and acetoin conferred reduced Arabidopsis protection to
      pathogen infection compared with seedlings exposed to VOCs from wild-type
      bacterial lines. Using transgenic and mutant lines of Arabidopsis, we provide
      evidence that the signaling pathway activated by volatiles from GB03 is dependent
      on ethylene, albeit independent of the salicylic acid or jasmonic acid signaling
      pathways. This study provides new insight into the role of bacteria VOCs as
      initiators of defense responses in plants.

PMID- 14976232
TI  - Molecular and biochemical analysis of two cDNA clones encoding dihydroflavonol-4
      reductase from Medicago truncatula.
AB  - Dihydroflavonol-4-reductase (DFR; EC1.1.1.219) catalyzes a key step late in the
      biosynthesis of anthocyanins, condensed tannins (proanthocyanidins), and other
      flavonoids important to plant survival and human nutrition. Two DFR cDNA clones
      (MtDFR1 and MtDFR2) were isolated from the model legume Medicago truncatula cv
      Jemalong. Both clones were functionally expressed in Escherichia coli, confirming
      that both encode active DFR proteins that readily reduce taxifolin
      (dihydroquercetin) to leucocyanidin. M. truncatula leaf anthocyanins were shown
      to be cyanidin-glucoside derivatives, and the seed coat proanthocyanidins are
      known catechin and epicatechin derivatives, all biosynthesized from
      leucocyanidin. Despite high amino acid similarity (79% identical), the
      recombinant DFR proteins exhibited differing pH and temperature profiles and
      differing relative substrate preferences. Although no pelargonidin derivatives
      were identified in M. truncatula, MtDFR1 readily reduced dihydrokaempferol,
      consistent with the presence of an asparagine residue at a location known to
      determine substrate specificity in other DFRs, whereas MtDFR2 contained an
      aspartate residue at the same site and was only marginally active on
      dihydrokaempferol. Both recombinant DFR proteins very efficiently reduced 5
      deoxydihydroflavonol substrates fustin and dihydrorobinetin, substances not
      previously reported as constituents of M. truncatula. Transcript accumulation for
      both genes was highest in young seeds and flowers, consistent with accumulation
      of condensed tannins and leucoanthocyanidins in these tissues. MtDFR1 transcript
      levels in developing leaves closely paralleled leaf anthocyanin accumulation.
      Overexpression of MtDFR1 in transgenic tobacco (Nicotiana tabacum) resulted in
      visible increases in anthocyanin accumulation in flowers, whereas MtDFR2 did not.
      The data reveal unexpected properties and differences in two DFR proteins from a
      single species.

PMID- 14976233
TI  - myo-inositol oxygenase offers a possible entry point into plant ascorbate
      biosynthesis.
AB  - Two biosynthetic pathways for ascorbate (l-ascorbic acid [AsA]; vitamin C) in
      plants are presently known, the mannose/l-galactose pathway and an l-GalUA
      pathway. Here, we present molecular and biochemical evidence for a possible
      biosynthetic route using myo-inositol (MI) as the initial substrate. A MI
      oxygenase (MIOX) gene was identified in chromosome 4 (miox4) of Arabidopsis
      ecotype Columbia, and its enzymatic activity was confirmed in bacterially
      expressed recombinant protein. Miox4 was primarily expressed in flowers and
      leaves of wild-type Arabidopsis plants, tissues with a high concentration of AsA.
      Ascorbate levels increased 2- to 3-fold in homozygous Arabidopsis lines
      overexpressing the miox4 open reading frame, thus suggesting the role of MI in
      AsA biosynthesis and the potential for using this gene for the agronomic and
      nutritional enhancement of crops.

PMID- 14976234
TI  - Functional characterization of allantoinase genes from Arabidopsis and a
      nonureide-type legume black locust.
AB  - The availability of nitrogen is a limiting factor for plant growth in most soils.
      Allantoin and its degradation derivatives are a group of soil heterocyclic
      nitrogen compounds that play an essential role in the assimilation, metabolism,
      transport, and storage of nitrogen in plants. Allantoinase is a key enzyme for
      biogenesis and degradation of these ureide compounds. Here, we describe the
      isolation of two functional allantoinase genes, AtALN (Arabidopsis allantoinase)
      and RpALN (Robinia pseudoacacia allantoinase), from Arabidopsis and black locust
      (Robinia pseudoacacia). The proteins encoded by those genes were predicted to
      have a signal peptide for the secretory pathway, which is consistent with earlier
      biochemical work that localized allantoinase activity to microbodies and
      endoplasmic reticulum (Hanks et al., 1981). Their functions were confirmed by
      genetic complementation of a yeast mutant (dal1) deficient in allantoin
      hydrolysis. The absence of nitrogen in the medium increased the expression of the
      genes. In Arabidopsis, the addition of allantoin to the medium as a sole source
      of nitrogen resulted in the up-regulation of the AtALN gene. The black locust
      gene (RpALN) was differentially regulated in cotyledons, axis, and hypocotyls
      during seed germination and seedling growth, but was not expressed in root
      tissues. In the trunk wood of a mature black locust tree, the RpALN gene was
      highly expressed in the bark/cambial region, but had no detectable expression in
      the sapwood or sapwood-heartwood transition zone. In addition, the gene
      expression in the bark/cambial region was up-regulated in spring and fall when
      compared with summer, suggesting its involvement in nitrogen mobilization.

PMID- 14976235
TI  - Manipulation of endogenous trypsin proteinase inhibitor production in Nicotiana
      attenuata demonstrates their function as antiherbivore defenses.
AB  - Evidence for the in planta defensive function of trypsin protease inhibitors
      (TPIs) comes from observations of enhanced herbivore resistance after
      heterologous TPI expression or the manipulation of signal cascades that activate
      numerous defense responses, including TPI production; no studies have altered the
      expression of an endogenous pi gene to examine defensive function. We isolated
      two genes with seven- and six-repeat TPI domains from Nicotiana attenuata from
      the potato (Solanum tuberosum) PI-II family. To determine whether endogenous TPIs
      in N. attenuata function defensively against the native herbivores, hornworm
      (Manduca sexta) and mirids (Tupiocoris notatus), we expressed 175 bp of the seven
      domain pi from N. attenuata in an antisense orientation in a TPI-producing
      genotype to reduce TPI expression and expressed the full-length seven-domain pi
      in a sense orientation under control of a constitutive promoter to restore TPI
      activity in a natural genotype from Arizona unable to produce TPIs. Constitutive
      and inducible TPI production in two antisense lines were diminished by 80% to 90%
      and 33% to 52%, respectively, and sense expression restored 67% of the activity
      found in the TPI-producing genotype after caterpillar attack in the TPI-deficient
      A genotype. Hornworm larvae fed on genotypes with low or no TPI activity grew
      faster, had higher survivorship, and produced heavier pupae than those that fed
      on genotypes with high TPI activity. T. notatus showed higher preference for
      genotypes with low or no TPI activity than for genotypes with high TPI levels. We
      conclude that endogenous TPIs are an effective defense against these native
      herbivores.

PMID- 14976236
TI  - The Arabidopsis cytosolic thioredoxin h5 gene induction by oxidative stress and
      its W-box-mediated response to pathogen elicitor.
AB  - The AtTRXh5 protein belongs to the cytosolic thioredoxins h family that, in
      Arabidopsis, contains eight members showing very distinct patterns and levels of
      expression. Here, we show that the AtTRXh5 gene is up-regulated during wounding,
      abscission, and senescence, as well as during incompatible interactions with the
      bacterial pathogen Pseudomonas syringae. By electrophoretic mobility shift
      assays, a binding activity on a W-box in the AtTRXh5 promoter region was found
      induced by treatments with the P. syringae-derived elicitor peptide flg22,
      suggesting that a WRKY transcription factor controls AtTRXh5 induction upon
      elicitor treatment. Remarkably, AtTRXh5 was up-regulated in plants overexpressing
      WRKY6. More generally, AtTRXh5 is induced in response to oxidative stress
      conditions. Collectively, our data indicate a possible implication of the
      cytosolic thioredoxin AtTRXh5 in response to pathogens and to oxidative stresses.
      In addition, this regulation is unique to AtTRXh5 among the thioredoxin h family,
      arguing in favor of a speciation rather than to a redundancy of the members of
      this multigenic family.

PMID- 14976237
TI  - Plastid lysophosphatidyl acyltransferase is essential for embryo development in
      Arabidopsis.
AB  - Lysophosphatidyl acyltransferase (LPAAT) is a pivotal enzyme controlling the
      metabolic flow of lysophosphatidic acid into different phosphatidic acids in
      diverse tissues. A search of the Arabidopsis genome database revealed five genes
      that could encode LPAAT-like proteins. We identified one of them, LPAAT1, to be
      the lone gene that encodes the plastid LPAAT. LPAAT1 could functionally
      complement a bacterial mutant that has defective LPAAT. Bacteria transformed with
      LPAAT1 produced LPAAT that had in vitro enzyme activity much higher on 16:0
      coenzyme A than on 18:1-coenzyme A in the presence of 18:1-lysophosphatidic acid.
      LPAAT1 transcript was present in diverse organs, with the highest level in green
      leaves. A mutant having a T-DNA inserted into LPAAT1 was identified. The
      heterozygous mutant has no overt phenotype, and its leaf acyl composition is
      similar to that of the wild type. Selfing of a heterozygous mutant produced
      normal-sized and shrunken seeds in the Mendelian ratio of 3:1, and the shrunken
      seeds could not germinate. The shrunken seeds apparently were homozygous of the T
      DNA-inserted LPAAT1, and development of the embryo within them was arrested at
      the heart-torpedo stage. This embryo lethality could be rescued by transformation
      of the heterozygous mutant with a 35S:LPAAT1 construct. The current findings of
      embryo death in the homozygous knockout mutant of the plastid LPAAT contrasts
      with earlier findings of a normal phenotype in the homozygous mutant deficient of
      the plastid glycerol-3-phosphate acyltransferase; both mutations block the
      synthesis of plastid phosphatidic acid. Reasons for the discrepancy between the
      contrasting phenotypes of the two mutants are discussed.

PMID- 14976238
TI  - Poplar peroxiredoxin Q. A thioredoxin-linked chloroplast antioxidant functional
      in pathogen defense.
AB  - Peroxiredoxins are ubiquitous thioredoxin- or glutaredoxin-dependent peroxidases,
      the function of which is to destroy peroxides. Peroxiredoxin Q, one of the four
      plant subtypes, is a homolog of the bacterial bacterioferritin comigratory
      proteins. We show here that the poplar (Populus tremula x Populus tremuloides)
      protein acts as a monomer with an intramolecular disulfide bridge between two
      conserved cysteines. A wide range of electron donors and substrates was tested.
      Unlike type II peroxiredoxin, peroxiredoxin Q cannot use the glutaredoxin or
      cyclophilin isoforms tested, but various cytosolic, chloroplastic, and
      mitochondrial thioredoxins are efficient electron donors with no marked
      specificities. The redox midpoint potential of the peroxiredoxin Q catalytic
      disulfide is -325 mV at pH 7.0, explaining why the wild-type protein is reduced
      by thioredoxin but not by glutaredoxin. Additional evidence that thioredoxin
      serves as a donor comes from the formation of heterodimers between peroxiredoxin
      Q and monocysteinic mutants of spinach (Spinacia oleracea) thioredoxin m.
      Peroxiredoxin Q can reduce various alkyl hydroperoxides, but with a better
      efficiency for cumene hydroperoxide than hydrogen peroxide and tertiary butyl
      hydroperoxide. The use of immunolocalization and of a green fluorescence protein
      fusion construct indicates that the transit sequence efficiently targets
      peroxiredoxin Q to the chloroplasts and especially to those of the guard cells.
      The expression of this protein and of type II peroxiredoxin is modified in
      response to an infection by two races of Melampsora larici-populina, the
      causative agent of the poplar rust. In the case of an hypersensitive response,
      the peroxiredoxin expression increased, whereas it decreased during a compatible
      interaction.

PMID- 14976239
TI  - A novel endo-beta-mannanase gene in tomato LeMAN5 is associated with anther and
      pollen development.
AB  - Endo-beta-mannanase (EC 3.2.1.78) is involved in cell wall disassembly and the
      weakening of plant tissues by degrading mannan polymers in the cell walls. Endo
      beta-mannanase genes are expressed in tomato (Lycopersicon esculentum) seeds
      (LeMAN1 and LeMAN2) and fruits (LeMAN3 and LeMAN4). A novel endo-beta-mannanase
      gene (termed LeMAN5) was found in the tomato genome by genome-walking PCR and
      bacterial artificial chromosome library screening. The 5'-upstream region of this
      endo-beta-mannanase gene contained four copies of the pollen-specific cis-acting
      elements POLLEN1LELAT52 (AGAAA). A GUS-reporter gene driven with the putative
      LeMAN5 promoter (-543 to +38) was activated in anthers and pollen of transgenic
      Arabidopsis, with the highest beta-glucuronidase activity detected in pollen.
      beta-Glucuronidase expression was detected in mature pollen retained in
      sporangia, discharged pollen, and elongating pollen tubes in transgenic
      Arabidopsis. Consistently, expression of LeMAN5 mRNA and endo-beta-mannnanase
      activity was detected in tomato anthers and pollen. In anthers, the highest mRNA
      expression and endo-beta-mannanase activity were detected during late stages of
      anther development, when pollen maturation occurred. Endo-beta-mannanase activity
      was present in discharged pollen, which was easily eluted in a buffer, indicating
      that the enzyme proteins are probably secreted from, and deposited on, the
      surface of pollen. These data suggest that the LeMAN5 endo-beta-mannanase is
      associated with anther and pollen development.

PMID- 14976240
TI  - E1A and E1B proteins inhibit inflammation induced by adenovirus.
AB  - Replication-defective human adenovirus (Ad) group C transducing vectors, most of
      which have the E1A, E1B, and E3 genes deleted, are highly inflammatory despite
      the fact that the parental viruses typically cause subclinical or mild
      infections. To investigate this paradox, the roles that the E1A, E1B, and E3
      genes play in inflammation were tested by using replication-incompetent viruses
      carrying a deletion of the preterminal protein gene. The viruses were injected
      into BALB/c mouse ears, and edema was monitored as a sensitive surrogate marker
      of inflammation. A virus deleted for the E1A 289R (transcription activating)
      protein was noninflammatory, and inhibited edema induced by empty virus
      particles. The E1A 243R and E1B 55-kDa (p53 binding) proteins play the most
      important roles in inhibition of inflammation by the noninflammatory virus. The
      E1B 19-kDa antiapoptotic protein inhibited edema when both the E1A 243R and E1B
      55-kDa proteins were expressed but strongly induced edema when only one was
      expressed. E3 proteins had their greatest effect on the inhibition of edema
      induced by the E1A 289R protein. The results support a model in which
      inflammation is countered through a mechanism that involves complex genetic
      interactions between Ad early region proteins and offer promise for the design
      and construction of noninflammatory Ad gene therapy vectors that are relatively
      easy to grow and purify.

PMID- 14976241
TI  - Two structural features of lambda integrase that are critical for DNA cleavage by
      multimers but not by monomers.
AB  - Despite many years of genetic and biochemical studies on the lambda integrase
      (Int) recombination system, it is still not known whether the Int protein is
      competent for DNA cleavage as a monomer. We have addressed this question, as part
      of a larger study of Int functions critical for the formation of higher-order
      complexes, by isolating "multimer-specific" mutants. We identify a pair of
      oppositely charged residues, E153 and R169, that comprise an intermolecular salt
      bridge within a functional Int multimer. Mutation of either of these residues
      significantly reduces both the cleavage of full-att sites and the resolution of
      Holliday junctions without compromising the cleavage of half-att site substrates.
      Allele-specific suppressor mutations were generated at these residues. Their
      interaction with wild-type Int on preformed Holliday junctions indicates that the
      mutated residues comprise an intermolecular salt bridge. We have also shown that
      the most C-terminal seven residues of Int, which comprise another previously
      identified subunit interface, inhibit DNA cleavage by monomeric but not
      multimeric Int. Taken together, our results lead us to conclude that Int can
      cleave DNA as a monomer. We also identify and discuss unique structural features
      of Int that act negatively to reduce its activity as a monomer and other features
      that act positively to enhance its activity as a multimer.

PMID- 14976242
TI  - The archaeal feast/famine regulatory protein: potential roles of its assembly
      forms for regulating transcription.
AB  - The classification feast/famine regulatory proteins (FFRPs) encompasses archaeal
      DNA-binding proteins with Escherichia coli transcription factors, the leucine
      responsive regulatory protein and the asparagine synthase C gene product. In this
      paper, we describe two forms of the archaeal FFRP FL11 (pot0434017), both
      assembled from dimers. When crystallized, a helical cylinder is formed with six
      dimers per turn. In contrast, in solution, disks are formed, most likely
      consisting of four dimers each; an observation by cryoelectron microscopy.
      Whereas each dimer binds a 13-bp sequence, different forms will discriminate
      between promoters, based on the numbers of repeating 13-bp sequences, and types
      of linkers inserted between them, which are either of 7-8 or approximately 18 bp.
      The amino acid sequences of these FFRPs are designed to form the same type of 3D
      structures, and the transition between their assembly forms is regulated by
      interaction with small molecules. These considerations lead us to propose a
      possible mechanism for regulating a number of genes by varying assembly forms and
      by combining different FFRPs into these assemblies, responding to environmental
      changes.

PMID- 14976243
TI  - Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the
      treatment of leukemias caused by oncogenic PTKs.
AB  - Abnormal protein tyrosine kinases (PTKs) cause many human leukemias. For example,
      BCR/ABL causes chronic myelogenous leukemia (CML), whereas FLT3 mutations
      contribute to the pathogenesis of acute myelogenous leukemia. The ABL inhibitor
      Imatinib (Gleevec, STI571) has remarkable efficacy for treating chronic phase
      CML, and FLT3 inhibitors (e.g., PKC412) show similar promise in preclinical
      studies. However, resistance to PTK inhibitors is a major emerging problem that
      may limit long-term therapeutic efficacy. Development of rational combination
      therapies will probably be required to effect cures of these and other neoplastic
      disorders. Here, we report that the mTOR inhibitor rapamycin synergizes with
      Imatinib against BCR/ABL-transformed myeloid and lymphoid cells and increases
      survival in a murine CML model. Rapamycin/Imatinib combinations also inhibit
      Imatinib-resistant mutants of BCR/ABL, and rapamycin plus PKC412 synergistically
      inhibits cells expressing PKC412-sensitive or -resistant leukemogenic FLT3
      mutants. Biochemical analyses raise the possibility that inhibition of 4E-BP1
      phosphorylation may be particularly important for the synergistic effects of PTK
      inhibitor/rapamycin combinations. Addition of a mitogen-activated protein kinase
      kinase inhibitor to rapamycin or rapamycin plus PTK inhibitor further increases
      efficacy. Our results suggest that simultaneous targeting of more than one
      signaling pathway required by leukemogenic PTKs may improve the treatment of
      primary and relapsed CML and/or acute myelogenous leukemia caused by FLT3
      mutations. Similar strategies may be useful for treating solid tumors associated
      with mutant and/or overexpressed PTKs.

PMID- 14976244
TI  - Mice deficient for soluble adenylyl cyclase are infertile because of a severe
      sperm-motility defect.
AB  - To acquire the ability to fertilize, spermatozoa undergo complex, but at present
      poorly understood, activation processes. The intracellular rise of cAMP produced
      by the bicarbonate-dependent soluble adenylyl cyclase (sAC) has been suggested to
      play a central role in initiating the cascade of the events that culminates in
      spermatozoa maturation. Here, we show that targeted disruption of the sAC gene
      does not affect spermatogenesis but dramatically impairs sperm motility, leading
      to male sterility. sAC mutant spermatozoa are characterized by a total loss of
      forward motility and are unable to fertilize oocytes in vitro. Interestingly,
      motility in sAC mutant spermatozoa can be restored on cAMP loading, indicating
      that the motility defect observed is not caused by a structural defect. We,
      therefore, conclude that sAC plays an essential and nonredundant role in the
      activation of the signaling cascade controlling motility and, therefore, in
      fertility. The crucial role of sAC in fertility and the absence of any other
      obvious pathological abnormalities in sAC-deficient mice may provide a rationale
      for developing inhibitors that can be applied as a human male contraceptive.

PMID- 14976245
TI  - K channel gating by an affinity-switching selectivity filter.
AB  - A universal property of ion channels is their ability to alternate stochastically
      between two permeation states, open and closed. This behavior is thought to be
      controlled by a steric "gate", a structure that physically impedes ion flow in
      the closed state and moves out of the way during channel opening. Experiments
      employing macroscopic currents in the Shaker K channel have suggested a
      cytoplasmic localization for the gate. Crystallographic structures of the KcsA K
      channel indeed reveal a cytoplasmic constriction, implying that the gate and
      selectivity filter are localized to opposite ends of the permeation pathway.
      However, analysis of K channel subconductance behavior has suggested a strict
      coupling between channel opening (gating) and permeation. The idea that the
      selectivity filter is the gate was therefore investigated by using Monte Carlo
      simulations. Gating is accomplished by allowing the filter to alternate
      stochastically between two conformations: a high-affinity state, which
      selectively binds K ions (but not Na ions) and traps them, and a completely
      nonselective, low-affinity state, which allows both Na and K ions to permeate.
      The results of these simulations indicate that affinity switching not only endows
      the selectivity filter with gating abilities, it also allows efficient permeation
      without jeopardizing ion selectivity. In this model, permeation and gating result
      from the same process.

PMID- 14976246
TI  - Impetus for sowing and the beginning of agriculture: ground collecting of wild
      cereals.
AB  - The Agricultural Revolution in Western Asia, which took place some 11,000 years
      ago, was a turning point in human history [Childe, V. G. (1952) New Light on the
      Most Ancient East (Routledge & Kegan Paul, London)]. In investigating the
      cultural processes that could have led from gathering to intentional cultivation,
      various authors have discussed and tested wild cereal harvesting techniques. Some
      argue that Near Eastern foragers gathered grains by means of sickle harvesting,
      uprooting, plucking (hand stripping), or beating into baskets [Hillman, G. C. &
      Davies, M. S. (1999) in Prehistory of Agriculture: New Experimental and
      Ethnographic Approaches, ed. Anderson, P. (The Institute of Archaeology,
      University of California, Los Angeles), pp. 70-102]. During systematic
      experiments, we found that archaeobotanical data from regional Neolithic sites
      support ground collection of grains by early hunter-gatherers. Ground collecting
      suits the natural shattering of wild species that ripen and drop grains at the
      beginning of summer. We show that continual collection off the ground from May to
      October would have provided surplus grains for deliberate sowing in more
      desirable fields, and facilitate the transition to intentional cultivation.
      Because ground gathering enabled collectors to observe that fallen seeds are
      responsible for the growth of new plants in late fall, they became aware of the
      profitability of sowing their surplus seeds for next year's food. Ground
      collecting of wild barley and wild wheat may comprise the missing link between
      seed collecting by hunter-gatherers and cereal harvesting by early farmers.

PMID- 14976247
TI  - Fluorescence-activated cell sorting (FACS) of Drosophila hemocytes reveals
      important functional similarities to mammalian leukocytes.
AB  - Drosophila is a powerful model for molecular studies of hematopoiesis and innate
      immunity. However, its use for functional cellular studies remains hampered by
      the lack of single-cell assays for hemocytes (blood cells). Here we introduce a
      generic method combining fluorescence-activated cell sorting and nonantibody
      probes that enables the selective gating of live Drosophila hemocytes from the
      lymph glands (larval hematopoietic organ) or hemolymph (blood equivalent). Gated
      live hemocytes are analyzed and sorted at will based on precise quantitation of
      fluorescence levels originating from metabolic indicators, lectins, reporters
      (GFP and beta-galactosidase) and antibodies. With this approach, we discriminate
      and sort plasmatocytes, the major hemocyte subset, from lamellocytes, an
      activated subset present in gain-of-function mutants of the Janus kinase and Toll
      pathways. We also illustrate how important, evolutionarily conserved, blood-cell
      regulatory molecules, such as calcium and glutathione, can be studied
      functionally within hemocytes. Finally, we report an in vivo transfer of sorted
      live hemocytes and their successful reanalysis on retrieval from single hosts.
      This generic and versatile fluorescence-activated cell sorting approach for
      hemocyte detection, analysis, and sorting, which is efficient down to one animal,
      should critically enhance in vivo and ex vivo hemocyte studies in Drosophila and
      other species, notably mosquitoes.

PMID- 14976248
TI  - Glycosylation-independent targeting enhances enzyme delivery to lysosomes and
      decreases storage in mucopolysaccharidosis type VII mice.
AB  - Enzyme-replacement therapy is an established means of treating lysosomal storage
      diseases. Infused therapeutic enzymes are targeted to lysosomes of affected cells
      by interactions with cell-surface receptors that recognize carbohydrate moieties,
      such as mannose and mannose 6-phosphate, on the enzymes. We have tested an
      alternative, peptide-based targeting system for delivery of enzymes to lysosomes
      in a murine mucopolysaccharidosis type VII (MPS VII) model. This strategy depends
      on the interaction of a fragment of insulin-like growth factor II (IGF-II), with
      the IGF-II binding site on the bifunctional, IGF-II cation-independent mannose 6
      phosphate receptor. A chimeric protein containing a portion of mature human IGF
      II fused to the C terminus of human beta-glucuronidase was taken up by MPS VII
      fibroblasts in a mannose 6-phosphate-independent manner, and its uptake was
      inhibited by the addition of IGF-II. Furthermore, the tagged enzyme was delivered
      effectively to clinically significant tissues in MPS VII mice and was effective
      in reversing the storage pathology. The tagged enzyme was able to reduce storage
      in glomerular podocytes and osteoblasts at a dose at which untagged enzyme was
      much less effective. This peptide-based, glycosylation-independent lysosomal
      targeting system may enhance enzyme-replacement therapy for certain human
      lysosomal storage diseases.

PMID- 14976249
TI  - Sister grouping of chimpanzees and humans as revealed by genome-wide phylogenetic
      analysis of brain gene expression profiles.
AB  - Gene expression profiles from the anterior cingulate cortex (ACC) of human,
      chimpanzee, gorilla, and macaque samples provide clues about genetic regulatory
      changes in human and other catarrhine primate brains. The ACC, a cerebral
      neocortical region, has human-specific histological features. Physiologically, an
      individual's ACC displays increased activity during that individual's performance
      of cognitive tasks. Of approximately 45,000 probe sets on microarray chips
      representing transcripts of all or most human genes, approximately 16,000 were
      commonly detected in human ACC samples and comparable numbers, 14,000-15,000, in
      gorilla and chimpanzee ACC samples. Phylogenetic results obtained from gene
      expression profiles contradict the traditional expectation that the non-human
      African apes (i.e., chimpanzee and gorilla) should be more like each other than
      either should be like humans. Instead, the chimpanzee ACC profiles are more like
      the human than like the gorilla; these profiles demonstrate that chimpanzees are
      the sister group of humans. Moreover, for those unambiguous expression changes
      mapping to important biological processes and molecular functions that
      statistically are significantly represented in the data, the chimpanzee clade
      shows at least as much apparent regulatory evolution as does the human clade.
      Among important changes in the ancestry of both humans and chimpanzees, but to a
      greater extent in humans, are the up-regulated expression profiles of aerobic
      energy metabolism genes and neuronal function-related genes, suggesting that
      increased neuronal activity required increased supplies of energy.

PMID- 14976250
TI  - A small molecular activator of cardiac hypertrophy uncovered in a chemical screen
      for modifiers of the calcineurin signaling pathway.
AB  - The calcium, calmodulin-dependent phosphatase calcineurin, regulates growth and
      gene expression of striated muscles. The activity of calcineurin is modulated by
      a family of cofactors, referred to as modulatory calcineurin-interacting proteins
      (MCIPs). In the heart, the MCIP1 gene is activated by calcineurin and has been
      proposed to fulfill a negative feedback loop that restrains potentially
      pathological calcineurin signaling, which would otherwise lead to abnormal
      cardiac growth. In a high-throughput screen for small molecules capable of
      regulating MCIP1 expression in muscle cells, we identified a unique 4
      aminopyridine derivative exhibiting an embedded partial structural motif of
      serotonin (5-hydroxytryptamine, 5-HT). This molecule, referred to as pyridine
      activator of myocyte hypertrophy, acts as a selective agonist for 5-HT(2A/2B)
      receptors and induces hypertrophy of cardiac muscle cells through a signaling
      pathway involving calcineurin and a kinase-dependent mechanism that inactivates
      class II histone deacetylases, which act as repressors of cardiac growth. These
      findings identify MCIP1 as a downstream target of 5-HT(2A/2B) receptor signaling
      in cardiac muscle cells and suggest possible uses for 5-HT(2A/2B) agonists and
      antagonists as modulators of cardiac growth and gene expression.

PMID- 14976251
TI  - Human tumor p53 mutations are selected for in mouse embryonic fibroblasts
      harboring a humanized p53 gene.
AB  - To date, there has been no way to examine induced human p53 gene mutations in
      cell cultures exposed to mutagenic factors, other than by restriction site
      analysis. Here, we used embryonic cells from our Hupki (human p53 knock-in) mouse
      strain to generate human p53 DNA-binding domain (DBD) mutations experimentally.
      Twenty cultures of untreated primary mouse Hupki fibroblasts and 20 short
      wavelength UV light (UVC)-treated cultures (20J/m(2)) were passaged >20 times.
      Established Hupki embryonic fibroblast cell lines (HUFs) were genotyped by
      dideoxy DNA sequencing of p53 exons 4-9. Seven of the HUFs harbored point
      mutations in the humanized p53 DBD. Of the 9 mutations (6 single- and 1 triple
      site mutation), 2 were at the most frequently mutated codons in human cancers
      (c.248 and c.273). The Affymetrix p53 GeneChip assay also readily identified the
      6 single-base substitutions. All mutations in HUFs from UV-treated cultures were
      at dipyrimidine sites, including 3 nontranscribed strand C -->T transitions. The
      mutant HUFs were deficient in p53 transactivation function, and missense mutants
      had high levels of nuclear p53 protein. In a second experiment, primary Hupki
      cells were exposed to the carcinogen aristolochic acid I (AAI). Five of 10
      cultures that became established within 2 months harbored p53 DBD mutations. All
      were transversions, including 4 A --> T substitutions on the nontranscribed
      strand, a hallmark of DNA mutation by AAI. We conclude that establishment of
      Hupki mouse fibroblasts in culture readily selects for p53 DBD mutations found in
      human tumors, providing a basis for generating experimental mutation patterns in
      human p53.

PMID- 14976252
TI  - Intact type 1 immunity and immune-associated coagulative responses in mice
      lacking IFN gamma-inducible fibrinogen-like protein 2.
AB  - Fibrinogen-like protein 2 (Fgl2, fibroleukin) is a leukocyte product that
      exhibits significant homology to secreted proteins of diverse function, including
      growth factors, lectins, and components of extracellular matrix. Prior studies
      found that Fgl2 is IFN gamma-inducible, possesses direct coagulant activity, and
      inhibits T cell proliferation and dendritic cell maturation in vitro. Here, we
      demonstrate that Fgl2 expression is up-regulated during type 1 immunity in vivo
      and establish that such up-regulation is IFN gamma-, signal transducer and
      activation of transcription protein 1-, and IFN response factor 1-dependent. To
      investigate functional roles for Fgl2 during type 1 immunity, we generated Fgl2
      deficient mice. Those animals are born at predicted Mendelian frequencies, appear
      overtly healthy, and contain normal numbers and frequencies of lymphoid cells.
      Although Fgl2 is IFN gamma-inducible and putatively regulates T cell
      activation/proliferation, we demonstrate that Fgl2-deficient and control mice
      exhibit similar degrees of T cell expansion, immunopathology, and/or pathogen
      burdens during protozoan (Toxoplasma gondii), bacterial (Yersinia enterocolitica,
      Listeria monocytogenes, and Mycobacterium tuberculosis), and viral (murine gamma
      herpesvirus-68 and Sendai) infections. Fgl2-deficient mice also reject allografts
      with similar kinetics as control mice. Moreover, despite prior reports that Fgl2
      functions as a procoagulant enzyme, we demonstrate that Fgl2-deficient and
      control mice produce similar levels of fibrin, a product of the coagulation
      cascade, during T. gondii infection and allograft rejection. Together, our
      findings suggest that Fgl2, although highly conserved and IFN gamma-inducible, is
      not a critical mediator of either type 1 immunity or immune-associated coagulant
      activity.

PMID- 14976253
TI  - Blue light-induced transcription of plastid-encoded psbD gene is mediated by a
      nuclear-encoded transcription initiation factor, AtSig5.
AB  - Light is one of the most important environmental factors regulating expression of
      photosynthesis genes. The plastid psbD gene encoding the photosystem II reaction
      center protein D2 is under the control of a unique blue light responsive promoter
      (BLRP) that is transcribed by a bacterial-type plastid RNA polymerase (PEP).
      Promoter recognition of PEP is mediated by one of the six nuclear-encoded sigma
      factors in Arabidopsis. The replacement of the plastid sigma factor associated
      with PEP may be the major mechanism for switching of plastid transcription
      pattern in response to environmental and developmental signals. This study
      demonstrates that AtSig5 is a unique sigma factor that is essential for psbD BLRP
      activity. A T-DNA insertional mutant with reduced AtSIG5 expression resulted in
      loss of primary transcripts from the psbD BLRP. Furthermore, transient
      overexpression of AtSig5 in dark-adapted protoplasts specifically elevated psbD
      and psbA transcription activities. On the other hand, overproduction of AtSig2
      enhanced the transcription of psbA gene and trnE operon, but not psbD
      transcription. The AtSIG5 gene is phylogenetically distinct from other plastid
      sigma factors, and its expression is induced exclusively by blue light. We
      propose that AtSig5 acts as a mediator of blue light signaling that specifically
      activates the psbD BLRP in response to blue light in Arabidopsis.

PMID- 14976254
TI  - The simultaneous evolution of author and paper networks.
AB  - There has been a long history of research into the structure and evolution of
      mankind's scientific endeavor. However, recent progress in applying the tools of
      science to understand science itself has been unprecedented because only recently
      has there been access to high-volume and high-quality data sets of scientific
      output (e.g., publications, patents, grants) and computers and algorithms capable
      of handling this enormous stream of data. This article reviews major work on
      models that aim to capture and recreate the structure and dynamics of scientific
      evolution. We then introduce a general process model that simultaneously grows
      coauthor and paper citation networks. The statistical and dynamic properties of
      the networks generated by this model are validated against a 20-year data set of
      articles published in PNAS. Systematic deviations from a power law distribution
      of citations to papers are well fit by a model that incorporates a partitioning
      of authors and papers into topics, a bias for authors to cite recent papers, and
      a tendency for authors to cite papers cited by papers that they have read. In
      this TARL model (for topics, aging, and recursive linking), the number of topics
      is linearly related to the clustering coefficient of the simulated paper citation
      network.

PMID- 14976255
TI  - Recycling of a regulatory protein by degradation of the RNA to which it binds.
AB  - When Bacillus subtilis is grown in the presence of excess tryptophan,
      transcription of the trp operon is regulated by binding of tryptophan-activated
      TRAP to trp leader RNA, which promotes transcription termination in the trp
      leader region. Transcriptome analysis of a B. subtilis strain lacking
      polynucleotide phosphorylase (PNPase; a 3'-to-5' exoribonuclease) revealed a
      striking overexpression of trp operon structural genes when the strain was grown
      in the presence of abundant tryptophan. Analysis of trp leader RNA in the PNPase(
      ) strain showed accumulation of a stable, TRAP-protected fragment of trp leader
      RNA. Loss of trp operon transcriptional regulation in the PNPase(-) strain was
      due to the inability of ribonucleases other than PNPase to degrade TRAP-bound
      leader RNA, resulting in the sequestration of limiting TRAP. Thus, in the case of
      the B. subtilis trp operon, specific ribonuclease degradation of RNA in an RNA
      protein complex is required for recycling of an RNA-binding protein. Such a
      mechanism may be relevant to other systems in which limiting concentrations of an
      RNA-binding protein must keep pace with ongoing transcription.

PMID- 14976256
TI  - Competition for self-peptide-MHC complexes and cytokines between naive and memory
      CD8+ T cells expressing the same or different T cell receptors.
AB  - To study competition between naive and memory T cells, we examined proliferation
      of adoptively transferred naive CD8(+) T cells in lymphopenic recipients or
      recipients containing a clonal population of CD8(+) T cells. We find a hierarchy
      in the extent of T cell proliferation that appears to correlate with the strength
      of T cell receptor (TCR)-self-peptide-MHC (pepMHC) interactions. CD8(+) T cells
      also proliferate in recipients containing a full complement of CD8(+) cells with
      a different TCR if the transferred T cells experience stronger TCR-self-pepMHC
      interactions than the resident T cells. Furthermore, CD8(+) T cells proliferate
      in recipients that contain memory CD8(+) cells with a different TCR, but in this
      case the relative strengths of TCR-self-pepMHC interactions are not as critical.
      In contrast, CD8(+) T cells do not proliferate significantly in recipients
      harboring naive or memory CD8(+) cells that bear the same TCR as the transferred
      cells. These results suggest that, among naive T cells and between naive and
      memory T cells, CD8(+) cells having the same TCR compete for both self-pepMHC and
      cytokines, whereas TCR-different CD8(+) cells compete for cytokines. These
      competitive relationships probably help maintain the size and TCR diversity of
      naive and memory T cell populations required for optimal immune responses.

PMID- 14976257
TI  - P2X7 receptors control 2-arachidonoylglycerol production by microglial cells.
AB  - Endogenous cannabinoid ligands (endocannabinoids) produced by neurons,
      astrocytes, and microglial cells activate cannabinoid receptors, the molecular
      target for marijuana's bioactive ingredient Delta(9)-tetrahydrocannabinol. The
      molecular mechanism underlying the production of the most abundant
      endocannabinoid, 2-arachidonoylglycerol (2-AG), is unclear. A prevalent
      hypothesis proposes that activation of metabotropic receptors coupled to the
      phosphatidylinositol-specific phospholipase C and diacylglycerol (DG) lipase
      pathway will systematically lead to increases in 2-AG production. Here, we show
      that ATP increases 2-AG production by cultured microglial cells in a
      phosphatidylinositol-specific phospholipase C and DG lipase-dependent manner.
      However, efficacious activation of metabotropic P2Y purinergic receptors coupled
      to phosphatidylinositol-specific phospholipase C does not increase 2-AG
      production. This suggests that ionotropic, and not metabotropic, purinergic
      receptors control 2-AG production at an unexpected enzymatic step of its
      metabolic pathway. We show that activation of P2X(7) ionotropic receptors, which
      are highly permeable to calcium, is necessary and sufficient to increase 2-AG
      production in microglial cells. We also show that the sustained rise in
      intracellular calcium induced by activation of P2X(7) receptors directly
      increases DG lipase activity while inhibiting the activity of monoacylglycerol
      lipase, the enzyme that degrades 2-AG. This inverse sensitivity of DG lipase and
      monoacylglycerol lipase to calcium constitutes an original and efficient modality
      for sustained accumulation of 2-AG. Because prolonged increases in 2-AG amounts
      in brain parenchyma are thought to orchestrate neuroinflammation, the enzymatic
      steps involved in 2-AG synthesis and degradation by microglial cells constitute
      appealing targets for therapy aimed at controlling exacerbated neuroinflammation.

PMID- 14976258
TI  - Targeted analysis and discovery of posttranslational modifications in proteins
      from methanogenic archaea by top-down MS.
AB  - For more complete characterization of DNA-predicted proteins (including their
      posttranslational modifications) a "top-down" approach using high-resolution
      tandem MS is forwarded here by its application to methanogens in both hypothesis
      driven and discovery modes, with the latter dependent on new automation
      benchmarks for intact proteins. With proteins isolated from ribosomes and whole
      cell lysates of Methanococcus jannaschii (approximately 1,800 genes) using a 2D
      protein fractionation method, 72 gene products were identified and characterized
      with 100% sequence coverage via automated fragmentation of intact protein ions in
      a custom quadrupole/Fourier transform hybrid mass spectrometer. Three incorrect
      start sites and two modifications were found, with one of each determined for
      MJ0556, a 20-kDa protein with an unknown methylation at approximately 50%
      occupancy in stationary phase cells. The separation approach combined with the
      quadrupole/Fourier transform hybrid mass spectrometer allowed targeted and
      efficient comparison of histones from M. jannaschii, Methanosarcina acetivorans
      (largest Archaeal genome, 5.8 Mb), and yeast. This finding revealed a striking
      difference in the posttranslational regulation of DNA packaging in Eukarya vs.
      the Archaea. This study illustrates a significant evolutionary step for the MS
      tools available for characterization of WT proteins from complex proteomes
      without proteolysis.

PMID- 14976259
TI  - Transgenic male mating advantage provides opportunity for Trojan gene effect in a
      fish.
AB  - Genetically modified (GM) strains now exist for many organisms, producing
      significant promise for agricultural production. However, if these organisms have
      some fitness advantage, they may also pose an environmental harm when released.
      High mating success of GM males relative to WT males provides such an important
      fitness advantage. Here, we provide documentation that GM male medaka fish
      modified with salmon growth hormone possess an overwhelming mating advantage. GM
      medaka offspring possess a survival disadvantage relative to WT, however. When
      both of these fitness components are included in our model, the transgene is
      predicted to spread if GM individuals enter wild populations (because of the
      mating advantage) and ultimately lead to population extinction (because of the
      viability disadvantage). Mating trials indicate that WT males use alternative
      mating tactics in an effort to counter the mating advantage of GM males, and we
      use genetic markers to ascertain the success of these alternative strategies.
      Finally, we model the impact of alternative mating tactics by WT males on
      transgene spread. Such tactics may reduce the rate of transgene spread, but not
      the outcome.

PMID- 14976260
TI  - Disruption of TRPM6/TRPM7 complex formation by a mutation in the TRPM6 gene
      causes hypomagnesemia with secondary hypocalcemia.
AB  - Impaired magnesium reabsorption in patients with TRPM6 gene mutations stresses an
      important role of TRPM6 (melastatin-related TRP cation channel) in epithelial
      magnesium transport. While attempting to isolate full-length TRPM6, we found that
      the human TRPM6 gene encodes multiple mRNA isoforms. Full-length TRPM6 variants
      failed to form functional channel complexes because they were retained
      intracellularly on heterologous expression in HEK 293 cells and Xenopus oocytes.
      However, TRPM6 specifically interacted with its closest homolog, the Mg(2+)
      permeable cation channel TRPM7, resulting in the assembly of functional
      TRPM6/TRPM7 complexes at the cell surface. The naturally occurring S141L TRPM6
      missense mutation abrogated the oligomeric assembly of TRPM6, thus providing a
      cell biological explanation for the human disease. Together, our data suggest an
      important contribution of TRPM6/TRPM7 heterooligomerization for the biological
      role of TRPM6 in epithelial magnesium absorption.

PMID- 14976261
TI  - Innate antiviral responses by means of TLR7-mediated recognition of single
      stranded RNA.
AB  - Interferons (IFNs) are critical for protection from viral infection, but the
      pathways linking virus recognition to IFN induction remain poorly understood.
      Plasmacytoid dendritic cells produce vast amounts of IFN-alpha in response to the
      wild-type influenza virus. Here, we show that this requires endosomal recognition
      of influenza genomic RNA and signaling by means of Toll-like receptor 7 (TLR7)
      and MyD88. Single-stranded RNA (ssRNA) molecules of nonviral origin also induce
      TLR7-dependent production of inflammatory cytokines. These results identify ssRNA
      as a ligand for TLR7 and suggest that cells of the innate immune system sense
      endosomal ssRNA to detect infection by RNA viruses.

PMID- 14976262
TI  - Species-specific recognition of single-stranded RNA via toll-like receptor 7 and
      8.
AB  - Double-stranded ribonucleic acid (dsRNA) serves as a danger signal associated
      with viral infection and leads to stimulation of innate immune cells. In
      contrast, the immunostimulatory potential of single-stranded RNA (ssRNA) is
      poorly understood and innate immune receptors for ssRNA are unknown. We report
      that guanosine (G)- and uridine (U)-rich ssRNA oligonucleotides derived from
      human immunodeficiency virus-1 (HIV-1) stimulate dendritic cells (DC) and
      macrophages to secrete interferon-alpha and proinflammatory, as well as
      regulatory, cytokines. By using Toll-like receptor (TLR)-deficient mice and
      genetic complementation, we show that murine TLR7 and human TLR8 mediate species
      specific recognition of GU-rich ssRNA. These data suggest that ssRNA represents a
      physiological ligand for TLR7 and TLR8.

PMID- 14976263
TI  - Nanos maintains germline stem cell self-renewal by preventing differentiation.
AB  - Despite much progress in understanding how extrinsic signaling regulates stem
      cell self-renewal, little is known about how cell-autonomous gene regulation
      controls this process. In Drosophila ovaries, germline stem cells (GSCs) divide
      asymmetrically to produce daughter GSCs and cystoblasts, the latter of which
      develop into germline cysts. Here, we show that removing the translational
      repressor Nanos from either GSCs or their precursors, the primordial germ cells
      (PGCs), causes both cell types to differentiate into germline cysts. Thus, Nanos
      is essential for both establishing and maintaining GSCs by preventing their
      precocious entry into oogenesis. These functions are likely achieved by
      repressing the translation of differentiation factors in PGCs and GSCs.

PMID- 14976265
TI  - Trigeminal neuralgia.

PMID- 14976264
TI  - Stress-dependent regulation of FOXO transcription factors by the SIRT1
      deacetylase.
AB  - The Sir2 deacetylase modulates organismal life-span in various species. However,
      the molecular mechanisms by which Sir2 increases longevity are largely unknown.
      We show that in mammalian cells, the Sir2 homolog SIRT1 appears to control the
      cellular response to stress by regulating the FOXO family of Forkhead
      transcription factors, a family of proteins that function as sensors of the
      insulin signaling pathway and as regulators of organismal longevity. SIRT1 and
      the FOXO transcription factor FOXO3 formed a complex in cells in response to
      oxidative stress, and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1
      had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce
      cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's
      ability to induce cell death. Thus, one way in which members of the Sir2 family
      of proteins may increase organismal longevity is by tipping FOXO-dependent
      responses away from apoptosis and toward stress resistance.

PMID- 14976266
TI  - Rectal cancer: mesorectal lymph nodes at MR imaging with USPIO versus
      histopathologic findings--initial observations.
AB  - PURPOSE: To compare histopathologic findings with appearances of mesorectal lymph
      nodes at magnetic resonance (MR) imaging with ultrasmall particles of iron oxide
      (USPIO) in rectal cancer. MATERIALS AND METHODS: Mesorectal lymph nodes in 12
      patients with adenocarcinoma of the rectum were evaluated with USPIO and high
      spatial-resolution MR imaging. Appearance and signal intensity of lymph nodes at
      T2- and T2*-weighted imaging were recorded before and after USPIO administration.
      Two radiologists visually assessed pattern of enhancement; interobserver
      agreement was tested with the kappa statistic. After total mesorectal excision,
      MR imaging of surgical specimens was performed, and it enabled node-by-node
      correlation with histopathologic findings. RESULTS: Appearances of 74 nodes at in
      vivo MR imaging were compared with histopathologic findings. Sixty-eight nodes
      were nonmalignant (34 were normal, 34 showed reactive changes); six nodes were
      malignant. Four patterns of USPIO uptake were demonstrated at T2*-weighted
      imaging: uniform low signal intensity, central low signal intensity, eccentric
      high signal intensity, and uniform high signal intensity. Two radiologists showed
      good interobserver agreement (kappa = 0.88, P <.01) in classification of nodes
      into these four categories. Sixty-five (96%) of 68 nonmalignant nodes showed
      uniform or central low-signal-intensity patterns; 16 (47%) of 34 reactive nodes
      showed central low-signal-intensity patterns. Compared with uniform low-signal
      intensity pattern, central low-signal-intensity pattern was more commonly
      observed in reactive nodes (P <.01, chi(2) test; positive predictive value, 67%;
      95% CI: 47%, 87%). Eccentric and uniform high-signal-intensity patterns were
      observed in lymph nodes that contained metastases larger than 1 mm in diameter.
      CONCLUSION: Mesorectal lymph nodes can be characterized by using USPIO and T2*
      weighted MR imaging. Uniform and central low-signal-intensity patterns are
      features of nonmalignant nodes. Reactive nodes frequently show central low signal
      intensity at T2*-weighted imaging.

PMID- 14976267
TI  - Research Governance: a barrier to ethical research?

PMID- 14976268
TI  - Managing malignant disease in patients with porphyria.
AB  - Certain types of porphyria have an increased incidence of malignant disease. In
      addition, patients with all forms of porphyria may develop malignant disease as a
      'normal life event'. The investigation and treatment of porphyric patients with
      malignant disease requires specific precautions to minimize the risk of an acute
      porphyric attack, and to ensure optimum treatment of the malignancy. We briefly
      review the biochemical basis, clinical features and current management of
      porphyria in cancer patients.

PMID- 14976269
TI  - Secondary prevention for coronary artery disease.
AB  - BACKGROUND: Secondary prevention of coronary artery disease is effective in
      reducing morbidity and mortality, but deficiencies in implementation and
      prescription bias have been identified. AIM: To assess progress in secondary
      prevention measures for coronary heart disease and whether there was a difference
      between patient subgroups with angina, post myocardial infarction or
      revascularization. DESIGN: Retrospective analysis. METHODS: Between 1997 and
      2001, data were collected on prophylactic prescribing, demographic and lifestyle
      information, at baseline and 1 year following attendance at a hospital-based,
      cardiac-nurse-led out-patient clinic. RESULTS: Patients (n = 945) were entered
      into the database at hospital discharge and 619 (72%) attended at 1 year. Aspirin
      and statin prescribing increased, though ACE inhibitor use was less. Mean total
      cholesterol at baseline reduced to 4.92 +/- 0.11 mmol/l (p < 0.001) in 2000, with
      a further reduction to 4.59 +/- 0.08 mmol/l at the 1-year visit in 2001 (p <
      0.001). The proportion of patients with total cholesterol < 5 mmol/l increased to
      38% in 2000, reaching 70% in 2001. Smokers at baseline were similar at around
      30%, although this had reduced to 10% in 2001 (p < 0.001). No change in weight
      was seen for patients with BMI >or=30 (p = NS). No significant differences were
      seen between patient subgroups (p = NS). DISCUSSION: Secondary prevention
      measures are improving, especially in prophylactic prescribing, lipid management
      and smoking cessation, although scope for further improvement remains. No
      difference was seen between the patient subgroups. Lifestyle measures need to be
      addressed to gain maximum benefit in addressing overall cardiovascular risk.

PMID- 14976270
TI  - Heart failure in a district general hospital: are target doses of beta-blockers
      realistic?
AB  - BACKGROUND: Carvedilol therapy reduces mortality in patients with chronic heart
      failure. Multi-centre studies suggest a low first dose failure rate and high
      levels of tolerability to carvedilol. Little is known, however, concerning the
      eligibility and tolerance to treatment with carvedilol within a district general
      hospital setting. AIM: To evaluate the eligibility and tolerance of patients with
      heart failure to carvedilol within a district general hospital. DESIGN:
      Prospective clinical audit analysis. METHODS: We assessed 100 heart failure
      patients eligibility to commence carvedilol therapy. In those who satisfied
      clinical criteria, we evaluated first dose failure rate, target dose achievement,
      reasons for intolerance, heart rate and blood pressure reduction and resource
      requirements over a six-month period. RESULTS: Of 100 patients, 16% had contra
      indications to commence carvedilol and 22% were receiving a beta-blocker as part
      of their existing heart failure therapy. Although 62% satisfied eligibility
      criteria, 1% refused therapy, thus 61% were initiated on carvedilol. The first
      dose failure rate was 11.5% and 6.6% of patients achieved 'target dose'. Mean
      heart rate and systolic blood pressure reductions were 15 (SE 1.2)bpm and 17 (SE
      1.7) mmHg, respectively. Resource requirements included 155 hours of work-time
      for a trained heart failure specialist nurse and doctor. CONCLUSIONS: In the
      general setting, eligible patients appear to display a high first dose failure
      rate, poor tolerance to higher doses and achievement of a 'target dose' of
      carvedilol. Responses to adrenergic blockade were similar to previously published
      data, irrespective of the final tolerated dose, suggesting that the concept of
      achieving a 'target dose' may not be clinically useful. Guidelines and treatment
      protocols for heart failure should reflect not only what is considered gold
      standard, but also what is practical in general hospitals.

PMID- 14976271
TI  - Patterns of cardiovascular reactivity in disease diagnosis.
AB  - BACKGROUND: Aberrations of cardiovascular reactivity (CVR), an expression of
      autonomic function, occur in a number of clinical conditions, but lack
      specificity for a particular disorder. Recently, a CVR pattern particular to
      chronic fatigue syndrome was observed. AIM: To assess whether specific CVR
      patterns can be described for other clinical conditions. METHODS: Six groups of
      patients, matched for age and gender, were evaluated with a shortened head-up
      tilt test: patients with chronic fatigue syndrome (CFS) (n = 20), non-CFS fatigue
      (F) (n = 15), neurally-mediated syncope (SY) (n = 21), familial Mediterranean
      fever (FMF) (n = 17), psoriatic arthritis (PSOR) (n = 19) and healthy subjects
      (H) (n = 20). A 10-min supine phase was followed by recording 600 cardiac cycles
      on tilt (5-10 min). Beat-to-beat heart rate (HR) and pulse transit time (PTT)
      were measured. Results were analysed using conventional statistics, recurrence
      plot analysis and fractal analysis. RESULTS: Multivariate analysis evaluated
      independent predictors of the CVR in each patient group vs. all other groups.
      Based on these predictors, equations were determined for a linear discriminant
      score (DS) for each group. The best sensitivities and specificities of the DS,
      consistent with disease-related phenotypes of CVR, were noted in the following
      groups: CFS, 90.0% and 60%; SY, 93.3% and 62.5%; FMF, 90.1% and 75.4%,
      respectively. DISCUSSION: Pathological disturbances may alter cardiovascular
      reactivity. Our data support the existence of disease-related CVR phenotypes,
      with implications for pathogenesis and differential diagnosis.

PMID- 14976272
TI  - Cost-effectiveness of cognitive behaviour therapy for patients with chronic
      fatigue syndrome.
AB  - BACKGROUND: There is some evidence that cognitive behaviour therapy (CBT) is
      efficacious in chronic fatigue syndrome (CFS), but little data on its cost
      effectiveness. DESIGN: Prospective economic analysis alongside a randomized
      clinical trial. METHODS: CFS patients were randomly assigned to CBT, guided
      support groups (SG), or the 'natural course' (NC, no protocol-based
      interventions). Patients were treated for 8 months and followed-up for another 6
      months. Costs per patient showing clinically significant improvement, based on
      the CIS fatigue scale, and costs per quality-adjusted life year, were determined
      for a time period of 14 months. RESULTS: Data were available for 171 patients at
      8 months and for 128 at 14 months. At 8 and 14 months, the percentages of
      improved patients were 31% and 27% for CBT, 9% and 11% for SG, and 12% and 20%
      for NC. Mean QALYs gained at 14 months were, for CBT, SG and NC, respectively,
      0.0737, -0.0018 and 0.0458. CBT and SG mean treatment costs were euro1490 and
      euro424. Other medical costs for CBT, SG, and NC, respectively, were euro324,
      euro623 and euro412 for the first period, and euro232, euro561 and euro378 for
      the second period. Non-medical costs for these periods for CBT, SG and NC were
      euro262, euro550, euro427 and euro226, euro439, euro287, respectively.
      Productivity costs were considerable, but not significantly different between
      groups. DISCUSSION: CBT was less costly and more effective than SG. Compared to
      NC, the baseline incremental cost-effectiveness of CBT was euro20 516 per CFS
      patient showing clinically significant improvement, and euro21 375 per QALY. The
      bootstrap ratios showed considerable uncertainty regarding the results. Future
      research should focus on productivity costs, and follow patients prospectively
      over a longer period.

PMID- 14976273
TI  - Fibrinogen, C-reactive protein and coronary heart disease: does Mendelian
      randomization suggest the associations are non-causal?

PMID- 14976274
TI  - Anorexia nervosa and chronic renal insufficiency: a prescription for disaster.
AB  - Our imaginary consultant, Professor McCance, is asked to explain the basis for
      four major acute electrolyte abnormalities in a young woman with long-standing
      anorexia nervosa. She has a severe degree of hypokalaemia (2.0 mmol/l) with renal
      potassium wasting, a contracted extracellular fluid volume with renal NaCl
      wasting, hyponatraemia (118 mmol/l) while excreting hypoosmolar urine, and
      metabolic acidosis with a normal plasma anion gap (pH 7.20, bicarbonate 9
      mmol/l). McCance begins his discussion by considering the basis for hypokalaemia,
      as this electrolyte disorder is potentially life-threatening. Its pathophysiology
      is linked to the other major findings, using principles of integrative physiology
      together with a deductive and quantitative analysis. Nevertheless, to reach his
      final diagnosis, he requires information about newer molecular discoveries. Not
      only is he able to suggest a likely diagnosis, but he also devises a novel long
      term plan for therapy.

PMID- 14976275
TI  - Controlling persistent atrial fibrillation.

PMID- 14976276
TI  - Temporary cardiac pacing.

PMID- 14976277
TI  - What's the target?

PMID- 14976278
TI  - Dr Scrooge's casebook.

PMID- 14976279
TI  - Supply without demand.

PMID- 14976280
TI  - National Science Foundation. NIST struggles to escape the knife.

PMID- 14976281
TI  - National Science Foundation. Colwell steps down, Bement named Acting Director.

PMID- 14976282
TI  - Biomedical research. MRC gets flexible and clinical in funding overhaul.

PMID- 14976283
TI  - Quantum physics. Big, hot molecules bridge the gap between normal and surreal.

PMID- 14976284
TI  - Emerging infectious diseases. Nipah virus (or a cousin) strikes again.

PMID- 14976285
TI  - Neuroscience. Imaging studies show how brain thinks about pain.

PMID- 14976286
TI  - 2004 annual meeting. RNA rules metabolite production.

PMID- 14976288
TI  - 2004 annual meeting. Batteries powered to order.

PMID- 14976289
TI  - 2004 annual meeting. Oceans policy is in for an overhaul.

PMID- 14976290
TI  - 2004 annual meeting. Science at the extremes?

PMID- 14976291
TI  - Water resources. As the West goes dry.

PMID- 14976292
TI  - Behavioral evolution. The evolution of the golden rule.

PMID- 14976293
TI  - Miguel Nicolelis profile. Brazil institute charts a new hemisphere for
      neuroscience.

PMID- 14976294
TI  - E.T. search. No din of alien chatter in our neighborhood.

PMID- 14976295
TI  - More on molecular electronics.

PMID- 14976296
TI  - Forensic science and academic science.

PMID- 14976297
TI  - International agricultural research.

PMID- 14976298
TI  - Bioethics. Is biomedical research too dangerous to pursue?

PMID- 14976299
TI  - Astronomy. Double pulsar jackpot.

PMID- 14976300
TI  - Neuroscience. The where and when of intention.

PMID- 14976301
TI  - Chemistry. Ions at the air/water interface.

PMID- 14976302
TI  - Molecular biology. Filling gaps in genome organization.

PMID- 14976303
TI  - Biomedicine. Will the real cholesterol transporter please stand up.

PMID- 14976304
TI  - Prebiotic amino acids as asymmetric catalysts.

PMID- 14976305
TI  - Empathy for pain involves the affective but not sensory components of pain.
AB  - Our ability to have an experience of another's pain is characteristic of empathy.
      Using functional imaging, we assessed brain activity while volunteers experienced
      a painful stimulus and compared it to that elicited when they observed a signal
      indicating that their loved one--present in the same room--was receiving a
      similar pain stimulus. Bilateral anterior insula (AI), rostral anterior cingulate
      cortex (ACC), brainstem, and cerebellum were activated when subjects received
      pain and also by a signal that a loved one experienced pain. AI and ACC
      activation correlated with individual empathy scores. Activity in the posterior
      insula/secondary somatosensory cortex, the sensorimotor cortex (SI/MI), and the
      caudal ACC was specific to receiving pain. Thus, a neural response in AI and
      rostral ACC, activated in common for "self" and "other" conditions, suggests that
      the neural substrate for empathic experience does not involve the entire "pain
      matrix." We conclude that only that part of the pain network associated with its
      affective qualities, but not its sensory qualities, mediates empathy.

PMID- 14976306
TI  - Placebo-induced changes in FMRI in the anticipation and experience of pain.
AB  - The experience of pain arises from both physiological and psychological factors,
      including one's beliefs and expectations. Thus, placebo treatments that have no
      intrinsic pharmacological effects may produce analgesia by altering expectations.
      However, controversy exists regarding whether placebos alter sensory pain
      transmission, pain affect, or simply produce compliance with the suggestions of
      investigators. In two functional magnetic resonance imaging (fMRI) experiments,
      we found that placebo analgesia was related to decreased brain activity in pain
      sensitive brain regions, including the thalamus, insula, and anterior cingulate
      cortex, and was associated with increased activity during anticipation of pain in
      the prefrontal cortex, providing evidence that placebos alter the experience of
      pain.

PMID- 14976307
TI  - Fragmentation in massive star formation.
AB  - Studies of evolved massive stars indicate that they form in a clustered mode.
      During the earliest evolutionary stages, these regions are embedded within their
      natal cores. Here we present high-spatial-resolution interferometric dust
      continuum observations disentangling the cluster-like structure of a young
      massive star-forming region. The derived protocluster mass distribution is
      consistent with the stellar initial mass function. Thus, fragmentation of the
      initial massive cores may determine the initial mass function and the masses of
      the final stars. This implies that stars of all masses can form via accretion
      processes, and coalescence of intermediate-mass protostars appears not to be
      necessary.

PMID- 14976308
TI  - Direct measurement of energy thresholds to conformational isomerization in
      tryptamine.
AB  - Stimulated emission pumping (SEP)-hole filling spectroscopy and SEP-induced
      population transfer spectroscopy have been used to place narrow bounds on the
      energy thresholds for isomerization between individual reactant-product isomer
      pairs involving the seven conformational minima of tryptamine. The thresholds for
      isomerizing conformer A to all six other conformations divided into three groups
      at 750 wavenumbers (cm-1)(A-->B, F), 1000 cm-1 [A-->C(2)], and 1280 to 1320 cm-1
      [A-->D, E, and C(1)]. The appearance of the first band and the absence of the
      band below it were used to place upper and lower bounds to the barrier heights
      for each process. The thresholds for A-->B and B-->A isomerizations were also
      combined to determine the relative energies of these two lowest energy minima.
      The combined data from all X-->Y isomerizations identify important isomerization
      pathways on the potential energy surface linking the minima.

PMID- 14976309
TI  - Formation of secondary organic aerosols through photooxidation of isoprene.
AB  - Detailed organic analysis of natural aerosols from the Amazonian rain forest
      showed considerable quantities of previously unobserved polar organic compounds,
      which were identified as a mixture of two diastereoisomeric 2-methyltetrols: 2
      methylthreitol and 2-methylerythritol. These polyols, which have the isoprene
      skeleton, can be explained by OH radical-initiated photooxidation of isoprene.
      They have low vapor pressure, allowing them to condense onto preexisting
      particles. It is estimated that photooxidation of isoprene results in an annual
      global production of about 2 teragrams of the polyols, a substantial fraction of
      the Intergovernmental Panel on Climate Change estimate of between 8 and 40
      teragrams per year of secondary organic aerosol from biogenic sources.

PMID- 14976310
TI  - Repeating seismic events in China.
AB  - About 10% of seismic events in and near China from 1985 to 2000 were repeating
      events not more than about 1 kilometer from each other. We cross-correlated
      seismograms from approximately 14,000 earthquakes and explosions and measured
      relative arrival times to approximately 0.01 second, enabling lateral location
      precision of about 100 to 300 meters. Such precision is important for seismic
      hazard studies, earthquake physics, and nuclear test ban verification.
      Recognition and measurement of repeating signals in archived data and the
      resulting improvement in location specificity quantifies the inaccuracy of
      current procedures for picking onset times and locating events.

PMID- 14976311
TI  - Regulation of cell migration by the C2 domain of the tumor suppressor PTEN.
AB  - PTEN is a tumor suppressor protein that dephosphorylates phosphatidylinositol
      3,4,5 trisphosphate and antagonizes the phosphatidylinositol-3 kinase signaling
      pathway. We show here that PTEN can also inhibit cell migration through its C2
      domain, independent of its lipid phosphatase activity. This activity depends on
      the protein phosphatase activity of PTEN and on dephosphorylation at a single
      residue, threonine(383). The ability of PTEN to control cell migration through
      its C2 domain is likely to be an important feature of its tumor suppressor
      activity.

PMID- 14976312
TI  - Recruitment and spreading of the C. elegans dosage compensation complex along X
      chromosomes.
AB  - To achieve X-chromosome dosage compensation, organisms must distinguish X
      chromosomes from autosomes. We identified multiple, cis-acting regions that
      recruit the Caenorhabditis elegans dosage compensation complex (DCC) through a
      search for regions of X that bind the complex when detached from X. The DCC
      normally assembles along the entire X chromosome, but not all detached regions
      recruit the complex, despite having genes known to be dosage compensated on the
      native X. Thus, the DCC binds first to recruitment sites, then spreads to
      neighboring X regions to accomplish chromosome-wide gene repression. From a large
      chromosomal domain, we defined a 793-base pair fragment that functions in vivo as
      an X-recognition element to recruit the DCC.

PMID- 14976313
TI  - An engineered pathway for the formation of protein disulfide bonds.
AB  - We have engineered a pathway for the formation of disulfide bonds. By imposing
      evolutionary pressure, we isolated mutations that changed thioredoxin, which is a
      monomeric disulfide reductase, into a [2Fe-2S] bridged dimer capable of
      catalyzing O2-dependent sulfhydryl oxidation in vitro. Expression of the mutant
      protein in Escherichia coli with oxidizing cytoplasm and secretion via the Tat
      pathway restored disulfide bond formation in strains that lacked the complete
      periplasmic oxidative machinery (DsbA and DsbB). The evolution of [2Fe-2S]
      thioredoxin illustrates how mutations within an existing scaffold can add a
      cofactor and markedly change protein function.

PMID- 14976314
TI  - The structure of a mycobacterial outer-membrane channel.
AB  - Mycobacteria have low-permeability outer membranes that render them resistant to
      most antibiotics. Hydrophilic nutrients can enter by way of transmembrane-channel
      proteins called porins. An x-ray analysis of the main porin from Mycobacterium
      smegmatis, MspA, revealed a homooctameric goblet-like conformation with a single
      central channel. This is the first structure of a mycobacterial outer-membrane
      protein. No structure-related protein was found in the Protein Data Bank. MspA
      contains two consecutive beta barrels with nonpolar outer surfaces that form a
      ribbon around the porin, which is too narrow to fit the thickness of the
      mycobacterial outer membrane in contemporary models.

PMID- 14976315
TI  - Use of CD134 as a primary receptor by the feline immunodeficiency virus.
AB  - Feline immunodeficiency virus (FIV) induces a disease similar to acquired
      immunodeficiency syndrome (AIDS) in cats, yet in contrast to human
      immunodeficiency virus (HIV), CD4 is not the viral receptor. We identified a
      primary receptor for FIV as CD134 (OX40), a T cell activation antigen and
      costimulatory molecule. CD134 expression promotes viral binding and renders cells
      permissive for viral entry, productive infection, and syncytium formation.
      Infection is CXCR4-dependent, analogous to infection with X4 strains of HIV.
      Thus, despite the evolutionary divergence of the feline and human lentiviruses,
      both viruses use receptors that target the virus to a subset of cells that are
      pivotal to the acquired immune response.

PMID- 14976316
TI  - Regulation of fasted blood glucose by resistin.
AB  - The association between obesity and diabetes supports an endocrine role for the
      adipocyte in maintaining glucose homeostasis. Here we report that mice lacking
      the adipocyte hormone resistin exhibit low blood glucose levels after fasting,
      due to reduced hepatic glucose production. This is partly mediated by activation
      of adenosine monophosphate-activated protein kinase and decreased expression of
      gluconeogenic enzymes in the liver. The data thus support a physiological
      function for resistin in the maintenance of blood glucose during fasting.
      Remarkably, lack of resistin diminishes the increase in post-fast blood glucose
      normally associated with increased weight, suggesting a role for resistin in
      mediating hyperglycemia associated with obesity.

PMID- 14976317
TI  - Gene targeting in stem cells from individuals with osteogenesis imperfecta.
AB  - Adult stem cells offer the potential to treat many diseases through a combination
      of ex vivo genetic manipulation and autologous transplantation. Mesenchymal stem
      cells (MSCs, also referred to as marrow stromal cells) are adult stem cells that
      can be isolated as proliferating, adherent cells from bones. MSCs can
      differentiate into multiple cell types present in several tissues, including
      bone, fat, cartilage, and muscle, making them ideal candidates for a variety of
      cell-based therapies. Here, we have used adeno-associated virus vectors to
      disrupt dominant-negative mutant COL1A1 collagen genes in MSCs from individuals
      with the brittle bone disorder osteogenesis imperfecta, demonstrating successful
      gene targeting in adult human stem cells.

PMID- 14976318
TI  - Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption.
AB  - Dietary cholesterol consumption and intestinal cholesterol absorption contribute
      to plasma cholesterol levels, a risk factor for coronary heart disease. The
      molecular mechanism of sterol uptake from the lumen of the small intestine is
      poorly defined. We show that Niemann-Pick C1 Like 1(NPC1L1) protein plays a
      critical role in the absorption of intestinal cholesterol. NPC1L1 expression is
      enriched in the small intestine and is in the brush border membrane of
      enterocytes. Although otherwise phenotypically normal, NPC1L1-deficient mice
      exhibit a substantial reduction in absorbed cholesterol, which is unaffected by
      dietary supplementation of bile acids. Ezetimibe, a drug that inhibits
      cholesterol absorption, had no effect in NPC1L1 knockout mice, suggesting that
      NPC1L1 resides in an ezetimibe-sensitive pathway responsible for intestinal
      cholesterol absorption.

PMID- 14976319
TI  - Nervy links protein kinase a to plexin-mediated semaphorin repulsion.
AB  - Cyclic nucleotides regulate axonal responses to a number of guidance cues through
      unknown molecular events. We report here that Drosophila nervy, a member of the
      myeloid translocation gene family of A kinase anchoring proteins (AKAPs),
      regulates repulsive axon guidance by linking the cyclic adenosine monophosphate
      (cAMP)-dependent protein kinase (PKA) to the Semaphorin 1a (Sema-1a) receptor
      Plexin A (PlexA). Nervy and PKA antagonize Sema-1a-PlexA-mediated repulsion, and
      the AKAP binding region of Nervy is critical for this effect. Thus, Nervy couples
      cAMP-PKA signaling to PlexA to regulate Sema-1a-mediated axonal repulsion,
      revealing a simple molecular mechanism that allows growing axons to integrate
      inputs from multiple guidance cues.

PMID- 14976320
TI  - Attention to intention.
AB  - Intention is central to the concept of voluntary action. Using functional
      magnetic resonance imaging, we compared conditions in which participants made
      self-paced actions and attended either to their intention to move or to the
      actual movement. When they attended to their intention rather than their
      movement, there was an enhancement of activity in the pre-supplementary motor
      area (pre-SMA). We also found activations in the right dorsal prefrontal cortex
      and left intraparietal cortex. Prefrontal activity, but not parietal activity,
      was more strongly coupled with activity in the pre-SMA. We conclude that activity
      in the pre-SMA reflects the representation of intention.

PMID- 14976321
TI  - Estimating the cost-effectiveness of stroke units in France compared with
      conventional care.
AB  - BACKGROUND AND PURPOSE: The incidence of stroke in France is estimated at between
      120 000 and 150 000 cases per year. This modeling study assessed the clinical and
      economic benefits of establishing specialized stroke units compared with
      conventional care. METHODS: Data from the Dijon stroke registry were used to
      determine healthcare trajectories according to the degree of autonomy and
      organization of patient care. The relative risks of death or institutionalization
      or death or dependence after passage through a stroke unit were compared with
      conventional care. These risks were then inserted with the costing data into a
      Markov model to estimate the cost-effectiveness of stroke units. RESULTS:
      Patients cared for in a stroke unit survive more trimesters without sequelae in
      the 5 years after hospitalization than those cared for conventionally (11.6
      versus 8.28 trimesters). The mean cost per patient at 5 years was estimated at 30
      983 for conventional care and 34 638 in a stroke unit. An incremental cost
      effectiveness ratio for stroke units of 1359 per year of life gained without
      disability was estimated. CONCLUSIONS: The cost-effectiveness ratio for stroke
      units is much lower than the threshold (53 400 ) of acceptability recognized by
      the international scientific community. This finding justifies organizational
      changes in the management of stroke patients and the establishment of stroke
      units in France.

PMID- 14976322
TI  - Appearance of early venous filling during intra-arterial reperfusion therapy for
      acute middle cerebral artery occlusion: a predictive sign for hemorrhagic
      complications.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the correlation
      between appearance of angiographic early venous filling during intra-arterial
      reperfusion therapy and posttherapeutic hemorrhagic complications. METHODS: For
      the past 7 years, 104 patients prospectively underwent superselective local
      angiography via a microcatheter before and during intra-arterial reperfusion
      therapy for acute middle cerebral artery occlusion to evaluate the presence or
      absence of early venous filling. In principle, reperfusion therapy was
      discontinued just after appearance of early venous filling for fear of
      hemorrhage. There were 2 types of early venous filling: early filling of the
      thalamostriate vein from the lenticulostriate arteries and that of the cortical
      vein from the cortical arteries. RESULTS: Among these 104 patients, 31 (29.8%)
      had early venous filling: 19 had early filling of the thalamostriate vein, and
      the other 12 had early filling of the cortical vein. Eight of the 19 patients
      (42.1%) and 2 of the 12 patients (16.7%) had massive hematoma with neurological
      worsening, whereas only 1 of the 73 patients (1.4%) without early venous filling
      had massive hematoma. There was a significant correlation between early venous
      filling and massive hematoma in both the deep (P<0.0001) and superficial
      (P=0.0019) middle cerebral artery territories. The sensitivity and specificity of
      the presence of early venous filling as an indicator of parenchymal hematoma were
      71% and 83%, respectively. None of the 31 ischemic areas with early venous
      filling could escape cerebral infarction. CONCLUSIONS: Appearance of early venous
      filling may indicate irreversible brain damage and may be a predictive sign for
      parenchymal hematoma.

PMID- 14976323
TI  - Potassium channel dysfunction in cerebral arteries of insulin-resistant rats is
      mediated by reactive oxygen species.
AB  - BACKGROUND AND PURPOSE: Insulin resistance (IR) increases the risk of stroke in
      humans. One possible underlying factor is cerebrovascular dysfunction resulting
      from altered K(+) channel function. Thus, the goal of this study was to examine
      K+ channel-mediated relaxation in IR cerebral arteries. METHODS: Experiments were
      performed on pressurized isolated middle cerebral arteries (MCAs) from fructose
      fed IR and control rats. RESULTS: Dilator responses to iloprost, which are BK(Ca)
      channel mediated, were reduced in the IR compared with control arteries (19+/-2%
      versus 33+/-2% at 10(-6) mol/L). Similarly, relaxation to the K(ATP) opener
      pinacidil was diminished in the IR MCAs (17+/-2%) compared with controls (38+/-2%
      at 10(-5) mol/L). IR also reduced the K(ATP) channel-dependent component in
      calcitonin gene-related peptide-induced dilation; however, the magnitude of the
      relaxation remained unchanged in IR because of a nonspecified K+ channel-mediated
      compensatory mechanism. In contrast, K(ir) channel-mediated relaxation elicited
      by increases in extracellular [K+] (4 to 12 mmol/L) was similar in the control
      and IR arteries. Blockade of the K(ir) and K(v) channels with Ba2+ and 4
      aminopyridine, respectively, constricted the MCAs in both experimental groups
      with no significant difference. Pretreatment of arteries with superoxide
      dismutase (200 U/mL) plus catalase (150 U/mL) restored the dilatory responses to
      iloprost and pinacidil in the IR arteries. Immunoblots showed that the
      expressions of the pore-forming subunits of the examined K+ channels are not
      altered by IR. CONCLUSIONS: IR induces a type-specific K+ channel dysfunction
      mediated by reactive oxygen species. The alteration of K(ATP) and BK(Ca) channel
      dependent vascular responses may be responsible for the increased risk of
      cerebrovascular events in IR.

PMID- 14976324
TI  - Disability measures in stroke: relationship among the Barthel Index, the
      Functional Independence Measure, and the Modified Rankin Scale.
AB  - BACKGROUND AND PURPOSE: Residual disability after stroke presents a major
      economic and humanistic burden. To quantify disability in patients, activities of
      daily living (ADL; Barthel Index [BI], and motor component of Functional
      Independence Measure [M-FIM]) and categorical disability measures (Modified
      Rankin Scale [MRS]) are used. The purpose of this study is to examine the
      predicting ability of ADL measures to global disability scale. METHODS: Kansas
      City Stroke Study data were used for the present study. Correlation coefficient,
      Kruskal-Wallis test, and polytomous logistic regression analysis were applied to
      examine the relationship between the ADL measure and global disability scale.
      Model fit statistics were examined to verify logistic regression appropriateness.
      A categorization scheme, which minimized the false-positive response rate, was
      selected as the optimal categorizing system. RESULTS: The 3 measures were highly
      correlated. Both BI and M-FIM differentiated disability better in lower than
      higher disability. In logistic regression, BI differentiated 4 disability levels;
      M-FIM differentiated 3 levels in MRS. However, on the basis of results of the
      Kruskal-Wallis and multiple comparison tests, we suspect that M-FIM may have the
      potential to predict MRS categories better with a different model. CONCLUSIONS:
      The proposed categorization scheme can serve as a translation between measures.
      However, because of the ceiling effect of BI and M-FIM, the translation could not
      be completed for all 6 levels of MRS. No apparent variation over time in the
      categorization scheme was observed. Further research needs to be conducted to
      develop better prediction models explaining the relationship between M-FIM and
      MRS.

PMID- 14976325
TI  - Frequency and determinants of poststroke dementia in Chinese.
AB  - BACKGROUND AND PURPOSE: Both dementia and stroke are major health problems in
      Chinese societies. Stroke is a frequent cause of dementia. Only a few studies
      have been published on poststroke dementia (PSDE), none of which has investigated
      a consecutive stroke cohort in Asian patient populations. The objective of this
      study was to examine the prevalence and clinical correlates of PSDE in Chinese
      stroke patients in Hong Kong. METHODS: Two hundred eighty stroke patients
      consecutively admitted to the medical wards of a university-affiliated regional
      hospital were interviewed by a psychiatrist 3 months after stroke. The presence
      of dementia and vascular dementia was diagnosed according to the Diagnostic and
      Statistical Manual, 4th edition. In addition, a wide range of demographic and
      clinical variables were examined. RESULTS: Fifty-five participants (20%) had
      PSDE. Univariate analysis found that PSDE was associated with age; level of
      education; prestroke Rankin Scale score; prestroke Informant Questionnaire on
      Cognitive Decline in the Elderly (IQCODE) score; National Institutes of Health
      Stroke Scale (NIHSS) best language score, dysarthria score, and total score;
      urinary incontinence; cortical infarct; leukoaraiosis; bilateral lesions; number
      of lesions; involvement of middle cerebral artery circulation; and cerebral
      atrophy index. Multivariate logistic regression suggested that prestroke IQCODE
      score, NIHSS total score, leukoaraiosis, involvement of middle cerebral artery
      territory, and cerebral atrophy index were independent risk factors of PSDE.
      After removal of 22 patients with prestroke dementia, which was defined as a
      prestroke IQCODE score > or =4.0, the frequency of PSDE dropped to 15.5%.
      Furthermore, involvement of the middle cerebral artery territory and cerebral
      atrophy index were replaced by level of education and bilateral lesions as
      independent predictors in the final logistic model. CONCLUSIONS: PSDE is common
      among Chinese stroke patients in Hong Kong. Its frequency is comparable to that
      in white populations. The clinical determinants of PSDE, after the exclusion of
      patients with prestroke dementia, include premorbid level of cognitive function,
      severity of stroke, leukoaraiosis, level of education, and bilateral lesions.

PMID- 14976326
TI  - Diffusion-weighted magnetic resonance imaging and neurobiochemical markers after
      aortic valve replacement: implications for future neuroprotective trials?
AB  - BACKGROUND AND PURPOSE: Cardiac surgery carries a high risk of neurological
      complications; therefore, these patients would be an appropriate target
      population for neuroprotective strategies. In this study, we evaluated
      postoperative diffusion-weighted imaging (DWI) as a potential surrogate marker
      for brain embolism and its relationship to neurobiochemical markers of brain
      injury. METHODS: Of a total of 45 consecutive patients undergoing aortic valve
      replacement, 37 completed preoperative and postoperative MRI. At the time of the
      MRI studies, serum S100beta and neuron-specific enolase concentrations were
      determined. Preexisting T2 and postoperative DWI lesion volumes were quantified.
      All patients had a blinded neurological examination before and after operation.
      RESULTS: New perioperative DWI lesions were present in 14 patients (38%), of whom
      only 3 developed focal neurological deficits. Eighteen small lesions were found
      in the white matter or vascular border zones in all but 2 patients with
      territorial stroke. The appearance of new DWI lesions correlated with age, pre
      existing T2 lesion volume, and postoperative S100beta concentrations on days 2 to
      4 after surgery. In a forward stepwise canonical discrimination model, only T2
      lesion volume was selected as a relevant variable. CONCLUSIONS: The incidence of
      postoperative DWI lesions in aortic valve replacement is high, and a suitable
      marker for neuroprotective trials would be a reduction in the number of such
      lesions. The volume of preexisting T2 lesions is related to the development of
      perioperative DWI lesions.

PMID- 14976327
TI  - Cerebral hemodynamics during the Valsalva maneuver: insights from ganglionic
      blockade.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to differentiate the mechanical
      effects of the Valsalva maneuver (VM) from the effects of changes in autonomic
      neural activity on cerebral hemodynamics in humans. METHODS: Nine healthy
      subjects performed the VM before and after autonomic ganglionic blockade with
      trimethaphan. Blood pressure (BP) was measured in the radial artery with an
      indwelling catheter or at the finger by Finapres. Cerebral blood flow (CBF)
      velocity was measured in the middle cerebral artery with transcranial Doppler;
      end-tidal CO2 was measured by mass spectrometry. RESULTS: Before blockade, during
      phase II of the VM, BP was reduced by 27% and CBF velocity was reduced by 33%
      (magnitude of changes during phase II divided by baseline measurements before the
      VM, P<0.05). Cerebrovascular conductance index (CVCI) increased by 21%. During
      phase IV, overshoot of CBF velocity was proportionately greater than that of BP
      (46% versus 30%). After blockade, during phase II, BP fell to a much greater
      degree by 50%, while CBF velocity decreased even more by 60% associated with an
      increase in CVCI by 33%. During phase IV, despite the absence of BP overshoot,
      CBF velocity still increased by 55% and CVCI by 33%. Both were significantly
      greater than before blockade. CONCLUSIONS: After ganglionic blockade, cerebral
      autoregulation is unable to prevent the substantial fall in CBF induced by the
      marked reduction in BP during the VM. Enhanced phase IV increases in both CBF
      velocity and CVCI reflect the intrinsic characteristics of cerebral hyperemic
      responses, which are likely modified in part by the removal of vasoconstrictor
      effects of autonomic neural activity elicited during the VM.

PMID- 14976328
TI  - Association of mean platelet volume with risk of stroke among 3134 individuals
      with history of cerebrovascular disease.
AB  - BACKGROUND AND PURPOSE: Mean platelet volume (MPV) is positively associated with
      measures of platelet activity and may be a useful indicator of the risk of
      vascular events in a variety of patient groups. METHODS: The association of MPV
      with the risk of stroke was assessed in the Perindopril Protection Against
      Recurrent Stroke Study (PROGRESS). All participants had a history of
      cerebrovascular disease at baseline, and analyses were adjusted for the effects
      of potential confounders. RESULTS: The study followed 3134 individuals for an
      average of 3.9 years (mean age, 65 years; 71% male; average MPV, 10.0 fL). Three
      hundred eighty-three individuals had 402 stroke events, and 160 had major
      coronary events. MPV was positively associated with the risk of stroke, with an
      11% increased relative risk (95% CI, 3% to 19%) of stroke per femtoliter greater
      MPV. There was no clear association of MPV with the risk of major coronary events
      (9% decreased relative risk; 95% CI, -23% to 7%). Perindopril did not alter MPV.
      CONCLUSIONS: MPV is an independent predictor of the risk of stroke among
      individuals with a history of stroke or transient ischemic attack. The
      measurement of MPV may add useful prognostic information for clinicians managing
      patients with a history of cerebrovascular disease.

PMID- 14976329
TI  - Blood pressure and stroke: an overview of published reviews.
AB  - BACKGROUND: The last few years have seen a considerable increase in the amount of
      information available concerning blood pressure (BP) and stroke associations.
      This article provides an overview of published reviews of the effects on stroke
      seen in trials of BP-lowering drugs and compares these with the results available
      from cohort studies. SUMMARY OF REVIEW: We present a review of major overviews of
      prospective cohort studies and an updated meta-analysis of >40 randomized
      controlled trials of BP lowering, which included >188 000 participants and
      approximately 6800 stroke events. Cohort studies now indicate that in the Asia
      Pacific region as well as in North America and Western Europe, each 10 mm Hg
      lower systolic BP is associated with a decrease in risk of approximately one
      third in subjects aged 60 to 79 years. The association is continuous down to
      levels of at least 115/75 mm Hg and is consistent across sexes, regions, and
      stroke subtypes and for fatal and nonfatal events. The proportional association
      is age dependent but is still a strong and positive association in those aged 80
      years. Data from randomized controlled trials, in which mean age at event was
      approximately 70 years, indicate that a 10 mm Hg reduction in systolic BP is
      associated with a reduction in risk of stroke of approximately one third. Per mm
      Hg systolic BP reduction, the benefits for stroke appear similar between agents,
      by baseline BP levels, and whether or not individuals have a past history of
      cardiovascular disease. There is, however, evidence of greater benefit with a
      larger BP reduction. CONCLUSIONS: The epidemiologically expected benefits of BP
      lowering for stroke risk reduction are broadly consistent across a range of
      different population subgroups. There are greater benefits from larger BP
      reductions, and initiating and maintaining BP reduction for stroke prevention is
      a more important issue than choice of initial agent.

PMID- 14976330
TI  - Mild to moderate hypothermia prevents microvascular basal lamina antigen loss in
      experimental focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Microvascular basal lamina damage occurs after cerebral
      ischemia and is important for the development of hemorrhage. The aim of this
      study was to determine whether hypothermia could maintain microvascular integrity
      in ischemic stroke. METHODS: Using the suture model, we subjected 12 rats to 3
      hours of focal ischemia and 24 hours of reperfusion. Six rats received
      postischemic normothermia (37 degrees C) and 6 received hypothermia (32 degrees C
      to 34 degrees C) for the reperfusion period; a group of 6 sham-operated animals
      without ischemia was used as control. Collagen type IV and hemoglobin were
      measured by Western blot analysis, matrix metalloproteinase (MMP)-2 and MMP-9 by
      gelatin zymography, and urokinase-type plasminogen activator (uPA) and tissue
      type plasminogen activator (tPA) by plasminogen-casein zymography. RESULTS:
      Hypothermia reduced basal lamina collagen type IV loss: 87+/-16% (hypothermia)
      versus 43+/-4% (normothermia) in basal ganglia and 74+/-16% versus 64+/-4% in
      cortex; hypothermia reduced hemorrhage from 431+/-65% (normothermia) to 241+/-28%
      (basal ganglia) (P<0.05). Hypothermia also reduced MMP-2, MMP-9, uPA, and tPA
      (basal ganglia: MMP-2: 71+/-20% [hypothermia] versus 109+/-3% [normothermia]; MMP
      9: 38+/-12% versus 115+/-4%; uPA activity: 310+/-86% versus 1019+/-22%; tPA
      activity: 61+/-17% versus 111+/-13%; cortex: MMP-2: 53+/-6% versus 116+/-1%; MMP
      9: 16+/-4% versus 123+/-3%; uPA: 180+/-27% versus 176+/-10%; tPA: 91+/-15% versus
      101+/-8%; each difference: P<0.001) (nonischemic control side=100%). CONCLUSIONS:
      Hypothermia maintains microvascular integrity and reduces hemorrhage and the
      activities of MMP-2, MMP-9, uPA, and tPA.

PMID- 14976331
TI  - Association between diabetes and stroke subtype on survival and functional
      outcome 3 months after stroke: data from the European BIOMED Stroke Project.

PMID- 14976332
TI  - Prognosis of cerebral vein and dural sinus thrombosis: results of the
      International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT).
AB  - BACKGROUND AND PURPOSE: The natural history and long-term prognosis of cerebral
      vein and dural sinus thrombosis (CVT) have not been examined previously by
      adequately powered prospective studies. METHODS: We performed a multinational (21
      countries), multicenter (89 centers), prospective observational study. Patients
      were followed up at 6 months and yearly thereafter. Primary outcome was death or
      dependence as assessed by modified Rankin Scale (mRS) score >2 at the end of
      follow-up. RESULTS: From May 1998 to May 2001, 624 adult patients with CVT were
      registered. At the end of follow-up (median 16 months), 356 patients (57.1%) had
      no symptom or signs (mRS=0), 137 (22%) had minor residual symptoms (mRS=1), and
      47 (7.5%) had mild impairments (mRS=2). Eighteen (2.9%) were moderately impaired
      (mRS=3), 14 (2.2%) were severely handicapped (mRS=4 or 5), and 52 (8.3%) had
      died. Multivariate predictors of death or dependence were age >37 years (hazard
      ratio [HR]=2.0), male sex (HR=1.6), coma (HR=2.7), mental status disorder
      (HR=2.0), hemorrhage on admission CT scan (HR=1.9), thrombosis of the deep
      cerebral venous system (HR=2.9), central nervous system infection (HR=3.3), and
      cancer (HR=2.9). Fourteen patients (2.2%) had a recurrent sinus thrombosis, 27
      (4.3%) had other thrombotic events, and 66 (10.6%) had seizures. CONCLUSIONS: The
      prognosis of CVT is better than reported previously. A subgroup (13%) of
      clinically identifiable CVT patients is at increased risk of bad outcome. These
      high-risk patients may benefit from more aggressive therapeutic interventions, to
      be studied in randomized clinical trials.

PMID- 14976333
TI  - Modulation of carcinogen metabolism and DNA interaction by calcium glucarate in
      mouse skin.
AB  - Almost all the polycyclic aromatic hydrocarbons (PAHs) require metabolic
      activation to exert their carcinogenic activity. Environmental carcinogen [(3)H]
      benzo[a]pyrene (BP) is carcinogenic only after its metabolic transformation to a
      reactive intermediate, which can then bind to cellular macromolecules. Inhibition
      of dimethylbenz anthracene- (DMBA-) DNA binding generally accompanied inhibition
      of tumor initiation as most inhibitors of initiation interfere with the metabolic
      activation of the initiator. The importance of carcinogen-DNA interaction and the
      enzymes involved in the metabolism of carcinogenic polycyclic hydrocarbons has
      led to a search for inhibitors that would be useful in modifying the cancer
      causing effects of the PAHs. We tested the effect of calcium glucarate (Cag), a
      naturally occurring nontoxic compound, on carcinogen metabolism and DNA
      interaction. Cag inhibited [(3)H] BP binding to both calf thymus DNA in vitro and
      to epidermal DNA in vivo. Application of Cag to mouse skin caused a dose
      dependent inhibition of [(3)H] BP binding to epidermal DNA. To establish the
      relevance of the in vivo results to the in vitro situation, we followed the in
      vitro effect of Cag on [(3)H] BP binding to calf thymus DNA and observed that Cag
      inhibited the [(3)H] BP binding to calf thymus DNA in the presence of microsomes
      prepared from animals treated with DMBA. We also studied related events like DNA
      synthesis and carcinogen metabolism. For assessing the DNA synthesis, thymidine
      kinase was used as marker. Cag caused a dose-dependent inhibition of DMBA-induced
      thymidine kinase activity. At the same time, Cag caused a marked inhibition of
      DMBA-induced aryl hydrocarbon hydroxylase (AHH) activity, an enzyme responsible
      for the metabolism of PAHs like BP, both in vivo and in vitro. Our study
      indicates that Cag exerted its antitumor effect possibly by inhibiting the
      carcinogen-DNA binding, which appears to be due to reduced DNA synthesis and AHH
      activity.

PMID- 14976334
TI  - Initiating activity of 4-chlorobiphenyl metabolites in the resistant hepatocyte
      model.
AB  - We recently reported that several mono- to tetrachlorinated biphenyls have
      initiating activity in the livers of Fischer 344 rats. In the present study, we
      investigated the metabolic activation of one of those compounds, 4-chlorobiphenyl
      (PCB 3). Monohydroxy (400 micromol/kg), dihydroxy (200 micromol/kg), and quinone
      (100 micromol/kg) metabolites of PCB 3 were evaluated for their initiating
      activity. Fischer 344 male rats were fasted for 4 days; 24 h after feeding again,
      they were injected (ip) with metabolites, vehicle, or diethylnitrosamine (DEN, 20
      or 40 mg/kg). All animals were treated with selection agents as follows: three
      daily p.o. doses of 2-acetylaminofluorene (2-AAF, 30 mg/kg), followed by a single
      p.o. dose of carbon tetrachloride (2 ml/kg) and three additional daily treatments
      of 2-AAF. Rats were killed 2 weeks after the last 2-AAF intubation. Livers were
      evaluated for changes in morphology, and the number and volume of gamma-glutamyl
      transpeptidase-positive foci were measured. Of the metabolites tested, only one
      monohydroxy and one quinoid metabolite showed initiating activity. The metabolic
      activation of PCB 3, therefore, proceeds via parahydroxylation and oxidation to
      the ortho 3,4-quinone, the ultimate carcinogen. This is the first report to
      demonstrate that specific PCB metabolites possess initiating activity in the
      rodent liver in vivo. The results support the conclusion that 4-OH PCB 3 and 3,4
      BQ PCB 3 act as proximate and ultimate carcinogenic metabolites resulting from
      the bioactivation of PCB 3 in rat liver.

PMID- 14976335
TI  - Kinetic modeling of beta-chloroprene metabolism: II. The application of
      physiologically based modeling for cancer dose response analysis.
AB  - beta-Chloroprene (2-chloro-1,3-butadiene; CD), which is used in the synthesis of
      polychloroprene, caused significant incidences of several tumor types in B6C3F1
      mice and Fischer rats, but not in Wistar rats or Syrian hamsters. This project
      investigates the relevance of the bioassay lung tumor findings to human health
      risk by developing a physiologically based toxicokinetic (PBTK) model and
      exploring a tissue specific exposure-dose-response relationship. Key steps
      included identification of the plausible genotoxic mode of action, experimental
      quantification of tissue-to-air partition coefficients, scaling of in vitro
      parameters of CD metabolism for input into the PBTK model, comparing the model
      with in vivo experimental gas uptake data, selecting an appropriate tissue
      dosimetric, and predicting a corresponding human exposure concentration. The
      total daily milligram amount of CD metabolized per gram of lung was compared with
      the animal bioassay response data, specifically combined bronchiolar
      adenoma/carcinoma. The faster rate of metabolism in mouse lung agreed with the
      markedly greater incidence of lung tumors compared with the other rodent species.
      A lung tissue dose was predicted for the combined rodent lung tumor bioassay data
      at a 10% benchmark response. A human version of the PBTK model predicted that the
      lung tissue dose in humans would be equivalent to continuous lifetime daily
      exposure of 23 ppm CD. PBTK model sensitivity analysis indicated greater
      dependence of model predictions of dosimetry on physiological than biochemical
      parameters. The combined analysis of lung tumor response across species using the
      PBTK-derived internal dose provides an improved alternative to default
      pharmacokinetic interspecies adjustments for application to human health risk
      assessment.

PMID- 14976336
TI  - Human CD34+ hematopoietic progenitor cells are sensitive targets for toxicity
      induced by 1,4-benzoquinone.
AB  - Chronic human exposure to benzene has been linked to several hematopoietic
      disorders, including leukemia and lymphomas. Certain benzene metabolites,
      including benzoquinone (BQ), are genotoxic and mutagenic. Bone marrow stem cells
      are targets for benzene-induced cytotoxicity and DNA damage that could result in
      changes to the genome of these progenitor cells, thereby leading to hematopoietic
      disorders and cancers. Human bone marrow CD34(+) hematopoietic progenitor cells
      (HPC) were exposed in vitro to 1,4-BQ to assess cytotoxicity, genotoxicity, and
      DNA damage responses and the molecular mechanisms associated with these events.
      CD34(+) HPC from 10 men and 10 women were exposed to 0, 1, 5, 10, 15, or 20
      microM of 1,4-BQ and analyzed 72 h later. Apoptosis and cytotoxicity were dose
      dependent, with exposure to 10 microM 1,4-BQ resulting in approximately 60%
      cytotoxicity relative to untreated controls. A significant increase in the
      percentage of micronucleated CD34(+) cells was detected in cultures treated with
      1,4-BQ. In addition, the p21 mRNA level was elevated in 1,4-BQ-treated cells,
      suggesting that human CD34(+) cells utilize the p53 pathway in response to 1,4-BQ
      induced DNA damage. However, there were no significant changes in mRNA levels of
      the DNA repair genes ku80, rad51, xpa, xpc, and ape1 as well as p53 following
      treatment with 1,4-BQ. Although interindividual variations were evident in the
      cellular response to 1,4-BQ, there was no gender difference in the response
      overall. These results show that human CD34(+) cells are sensitive targets for
      1,4-BQ toxicity that use the p53 DNA damage response pathway in response to
      genotoxic stress. Human CD34(+) HPC will be useful for testing the toxicity of
      other benzene metabolites and various hematotoxic chemicals.

PMID- 14976337
TI  - Activation of the aryl hydrocarbon receptor diminishes the memory response to
      homotypic influenza virus infection but does not impair host resistance.
AB  - Although suppression of a primary immune response by aryl hydrocarbon receptor
      (AhR) ligands is well known, few studies have explicitly examined the effects of
      AhR agonists on immunological memory. Therefore, the goal of this study was to
      characterize the anamnestic response to influenza virus in mice exposed to the
      most potent AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mice were
      given a single dose of TCDD, which caused suppression of the primary response,
      and kinetics of the recall antibody and CD8(+) T cell responses to homotypic
      infection were monitored. Two to three months after primary infection, virus
      specific IgG levels were suppressed in mice treated with TCDD, and remained
      suppressed after reinfection. In contrast, IgA levels were enhanced in the TCDD
      treated group. The recall response of virus-specific CD8(+) T cells was also
      suppressed, as the number of virus-specific memory CD8(+) T cells was diminished,
      and the kinetics of the recall response was delayed. No morbidity or mortality
      was observed in vehicle- or TCDD-treated mice, and mice in both groups cleared
      the virus within three days after reinfection. Thus, with regard to understanding
      how activation of the AhR during a primary immune response affects the generation
      of immunological memory, our data present a mixed story. On one hand, TCDD
      treatment reduced the primary response, resulting in lower levels of virus
      specific IgG and diminution of the memory CD8 pool. However, the secondary
      response to homotypic infection was nevertheless host-protective. These findings
      have implications for determining the mechanisms by which AhR ligands adversely
      affect lymphocyte function and understanding the mechanisms that control the
      acquisition of immunological memory.

PMID- 14976338
TI  - Enhanced rat Hershberger assay appears reliable for detection of not only (anti
      )androgenic chemicals but also thyroid hormone modulators.
AB  - Development of an internationally recognized standard for the Hershberger assay
      as a screening tool to detect potential (anti-)androgenic chemicals is in
      progress. In the present preliminary study, we evaluated the reliability of the
      enhanced Hershberger assay to detect thyroid hormone modulating activity, while
      concentrating attention on possible confounding influence on evaluation of (anti
      )androgenic activity. Castrated or testosterone propionate (TP; 0.2 or 0.25
      mg/kg/day)-injected castrated male Crj:CD(SD) IGS rats (seven weeks of age) were
      dosed for 10 days by oral gavage with vehicle (corn oil) or the following
      chemicals: propylthiouracil (PTU; 2.5 mg/kg/day), a potent inhibitor of thyroid
      hormone synthesis, phenobarbital (PB; 125 mg/kg/day) and 2,2-bis(4-chlorophenyl)
      1,1-dichloroethylene (p,p'-DDE; 100 mg/kg/day), two hepatic enzyme inducers that
      enhance the clearance of thyroid hormones. PTU markedly increased thyroid
      weights, and decreased serum T3 and T4, and increased serum TSH, also causing
      marked microscopic alteration of the thyroid gland. In comparison, PB and p,p'
      DDE only significantly affect serum T4 and revealed some histopathological
      findings. The alterations appeared to be more robust in the presence of TP.
      Furthermore, data for p,p'-DDE demonstrated its anti-androgenic effects, whereas
      PTU and PB had little or no effects on the weights of androgen-related accessory
      glands/tissues: the ventral prostate, dorso-lateral prostate, seminal vesicles
      with coagulating glands, glans penis, Cowper's glands, and levator ani plus
      bulbocavernosus (LABC) muscles. Weight of the LABC muscles was decreased by PB
      treatment in TP-treated castrated rats. These findings in the present study
      suggests that the enhanced Hershberger assay, with evaluation of thyroid
      histopathology and weights, and hormone levels, appears to be reliable for
      screening for not only (anti-)androgenic chemicals but also thyroid hormone
      modulators. In order to evaluate whether the sensitivity and specificity of such
      a thyroid assay is great enough for routine screening purposes, future
      experiments including dose-response studies using lower dose levels have to be
      performed.

PMID- 14976339
TI  - Kinetic modeling of beta-chloroprene metabolism: I. In vitro rates in liver and
      lung tissue fractions from mice, rats, hamsters, and humans.
AB  - Beta-chloroprene (2-chloro-1,3-butadiene, CD) is carcinogenic by inhalation
      exposure to B6C3F1 mice and Fischer F344 rats but not to Wistar rats or Syrian
      hamsters. The initial step in metabolism is oxidation, forming a stable epoxide
      (1-chloroethenyl)oxirane (1-CEO), a genotoxicant that might be involved in rodent
      tumorigenicity. This study investigated the species-dependent in vitro kinetics
      of CD oxidation and subsequent 1-CEO metabolism by microsomal epoxide hydrolase
      and cytosolic glutathione S-transferases in liver and lung, tissues that are
      prone to tumor induction. Estimates for Vmax and Km for cytochrome P450-dependent
      oxidation of CD in liver microsomes ranged from 0.068 to 0.29 micromol/h/mg
      protein and 0.53 to 1.33 microM, respectively. Oxidation (Vmax/Km) of CD in liver
      was slightly faster in the mouse and hamster than in rats or humans. In lung
      microsomes, Vmax/Km was much greater for mice compared with the other species.
      The Vmax and Km estimates for microsomal epoxide hydrolase activity toward 1-CEO
      ranged from 0.11 to 3.66 micromol/h/mg protein and 20.9 to 187.6 microM,
      respectively, across tissues and species. Hydrolysis (Vmax/Km) of 1-CEO in liver
      and lung microsomes was faster for the human and hamster than for rat or mouse.
      The Vmax/Km in liver was 3 to 11 times greater than in lung. 1-CEO formation from
      CD was measured in liver microsomes and was estimated to be 2-5% of the total CD
      oxidation. Glutathione S-transferase-mediated metabolism of 1-CEO in cytosolic
      tissue fractions was described as a pseudo-second order reaction; rates were
      0.0016-0.0068/h/mg cytosolic protein in liver and 0.00056-0.0022 h/mg in lung.
      The observed differences in metabolism are relevant to understanding species
      differences in sensitivity to CD-induced liver and lung tumorigenicity.

PMID- 14976340
TI  - Evaluation of a rat model versus a physiologically based extraction test for
      assessing phenanthrene bioavailability from soils.
AB  - The soil matrix can impact the bioavailability of soil-bound organic chemicals,
      and this impact is governed in part by soil properties such as organic carbon
      (OC) content, clay minerals, and pH. Recently, a physiologically based extraction
      test (PBET) was developed to predict the bioavailability of soil-bound organic
      chemicals. In the current study, the bioavailability of phenanthrene (PA) from
      laboratory-treated soils varying in OC content, clay, and pH was investigated
      using an in vivo rat model and an in vitro PBET. The relationship between these
      two approaches was also examined. In the in vivo assay, soils and corn oil
      containing equivalent levels of PA were administered to Sprague-Dawley rats by
      gavage at two dose levels: 400 and 800 mg/kg body weight. Equivalent doses were
      given via intravenous injection (i.v.). The areas under the blood concentration
      versus-time curves (AUC) were measured, and the absolute and relative
      bioavailabilities of PA were determined for each soil. In the PBET tests, one g
      of each soil was extracted by artificial saliva, gastric juice, duodenum juice,
      and bile. The fraction of PA mobilized from each soil was quantified. The AUCs of
      PA in all soils were significantly lower than those following iv injection (p <
      0.05), indicating that the soil matrix could reduce the bioavailability of PA
      from soil. There were obvious trends of soils with higher OC content and clay
      content, resulting in the lower bioavailability of PA from soil. A significant
      correlation (p < 0.05) was observed between the fraction of PA mobilized from
      soil in the PBET and its in vivo bioavailability. The data also showed that the
      absolute bioavailability of PA from corn oil was low: approximately 25%. These
      results suggest that PBET assay might be a useful alternative in predicting
      bioavailability of soil-bound organic chemicals. However, due to the limited soil
      types and use of one chemical vs. a variety of contaminants and soil properties
      in the environment, further efforts involving more chemicals and soil types are
      needed to validate this surrogate method.

PMID- 14976341
TI  - Altered AP-1 (activating protein-1) activity and c-jun activation in T cells
      exposed to the amide class herbicide 3,4-dichloropropionanilide (DCPA).
AB  - 3,4-Dichloropropionanilide (DCPA), the active ingredient of some postemergence
      herbicides, has been demonstrated to inhibit several immune system functions
      including cytokine production by T cells. The central role of cytokines in
      regulating the immune response suggests a possible mechanism by which DCPA
      inhibits the immune system. Since interleukin (IL)-2 is critical in regulating
      many immune functions, we chose to investigate the effect of DCPA on this
      cytokine. Using the human T lymphoma line, Jurkat, stimulated with phorbol-12
      myristate acetate (PMA) and the calcium ionophore A23187 (Io), we determined that
      DCPA exposure decreased IL-2 secretion and mRNA levels in a dose dependent
      manner. We hypothesized that DCPA affected one or more of the transcription
      factors that regulate IL-2 gene transcription. Activating protein 1(AP-1) is a
      transcription factor that has been demonstrated to be required for optimal IL-2
      gene transcription. Electrophoretic mobility shift assays (EMSAs) demonstrated a
      decreased level of AP-1 DNA binding activity in DCPA-exposed Jurkat cells
      compared to control cells from 30 min to 2 h after stimulation. The altered AP-1
      DNA binding kinetics was associated with a decrease in c-jun protein in these
      cells at 1 and 2 h after exposure and a decreased level of phosphorylated c-jun
      at 1-4 h after exposure. These results suggest a possible mechanism for DCPA
      induced IL-2 inhibition; alteration in the activation of the c-jun component of
      AP-1.

PMID- 14976342
TI  - Rotenone-induced apoptosis is mediated by p38 and JNK MAP kinases in human
      dopaminergic SH-SY5Y cells.
AB  - Rotenone is a naturally derived pesticide that has recently been shown to evoke
      the behavioral and pathological symptoms of Parkinson's disease in animal models.
      Though rotenone is known to be an inhibitor of the mitochondrial complex I
      electron transport chain, little is known about downstream pathways leading to
      its toxicity. We used human dopaminergic SH-SY5Y cells to study mechanisms of
      rotenone-induced neuronal cell death. Our results suggest that rotenone, at
      nanomolar concentrations, induces apoptosis in SH-SY5Y cells that is caspase
      dependent. Furthermore, rotenone treatment induces phosphorylation of c-Jun, the
      c-Jun N-terminal protein kinase (JNK), and the p38 mitogen activated protein
      (MAP) kinase, indicative of activation of the p38 and JNK pathways. Importantly,
      expression of dominant interfering constructs of the JNK or p38 pathways
      attenuated rotenone-induced apoptosis. These data suggest that rotenone induces
      apoptosis in the dopaminergic SH-SY5Y cells that requires activation of the JNK
      and p38 MAP kinases and caspases. These studies provide insights concerning the
      molecular mechanisms of rotenone-induced apoptosis in neuronal cells.

PMID- 14976343
TI  - Correlation of tumors with DNA adducts from methyl eugenol and tamoxifen in rats.
AB  - Data on percent tumors in male rats after administration of methyl eugenol,
      obtained from the National Toxicology Program, or tamoxifen were plotted on a
      linear scale for percent tumors against the dose on a logarithmic scale. Data on
      (32)P-postlabelled DNA adducts were plotted on the same graphs for each of these
      two compounds in order to correlate adduct formation and tumor incidence with
      dose. The resulting graph for methyl eugenol showed a linear response for both
      adduct formation and tumor incidence. The threshold dose of administered methyl
      eugenol for adduct formation (zero adducts) was 10(19.3) molecules of methyl
      eugenol/kg/day, which compared with a threshold of 10(20.1) molecules of methyl
      eugenol/kg/day for tumor formation; however, 30 adducts/10(8) nucleotides was the
      threshold for tumor formation. The dose of tamoxifen for adduct formation fit an
      exponential plot slightly better than a linear plot, but reached minimal values
      close to the threshold of 10(18.7) molecules of tamoxifen/kg/day for tumor
      formation. These data confirm that tumor formation coincides with adduct
      formation and that both have thresholds, or at least reach minimal values, above
      levels to which humans are exposed. Although the threshold dose for tumor
      formation from tamoxifen is only about 10x above the dose received by women at
      risk for breast cancer, this should be an adequate safety margin. The safety
      factor for methyl eugenol is several orders of magnitude; therefore, there should
      be no cause for concern for humans at current levels of exposure.

PMID- 14976344
TI  - Molecular switch circuits in toxicology: a dimmer switch for dioxin.

PMID- 14976345
TI  - Inorganic cadmium- and arsenite-induced malignant transformation of human bladder
      urothelial cells.
AB  - Arsenic and cadmium (Cd(+2)) are human carcinogens, and epidemiological studies
      have implicated both pollutants in the development of urinary bladder cancer.
      Despite this epidemiological base, it is unknown if either Cd(+2) or arsenite
      (As(+3)) can directly cause the malignant transformation of human urothelial
      cells. The goal of this study was to determine if Cd(+2) and/or As(+3) are able
      to cause the malignant transformation of human urothelial cells. The strategy
      employed was to expose the nontumorigenic urothelial cell line UROtsa to long
      term in vitro exposure to Cd(+2) and As(+3), with the endpoint being the ability
      of the cells to form colonies in soft agar and tumors when heterotransplanted
      into nude mice. It was demonstrated that a long-term exposure to either 1 M
      Cd(+2) or 1 M As(+3) resulted in the selection of cells that were able to form
      colonies in soft agar and tumors when heterotransplanted into nude mice. The
      histology of the tumor heterotransplants produced by UROtsa cells malignantly
      transformed by Cd(+2) had epithelial features consistent with those of a classic
      transitional-cell carcinoma of the bladder. The histology of the tumor
      heterotransplants produced by cells malignantly transformed by As(+3) was unique
      in that the cells displayed a prominent squamoid differentiation.

PMID- 14976346
TI  - Biliary secretory function in rats chronically intoxicated with aluminum.
AB  - The effects of a chronic aluminum (Al) exposure on biliary secretory function,
      with special emphasis on hepatic handling of non-bile salt organic anions, was
      investigated. Male Wistar rats received, intraperitoneally, either 27 mg/kg body
      weight of Al, as Al hydroxide [Al (+) rats], or the vehicle saline [Al (-) rats]
      three times a week for 3 months. Serum and hepatic Al levels were increased by
      the treatment (approximately 9- and 4-fold, respectively). This was associated
      with enhanced malondialdehyde formation (+110%) and a reduction in GSH content (
      17%) and in the activity of the antioxidant enzymes catalase (-84%) and GSH
      peroxidase (-46%). Bile flow (-23%) and the biliary output of bile salts (-39%),
      cholesterol (-43%), and proteins (-38%) also decreased. Compartmental analysis of
      the plasma decay of the model organic anion bromosulphophthalein revealed that
      sinusoidal uptake and canalicular excretion of the dye were significantly
      decreased in Al (+) rats (-53 and -43%, respectively). Expression of multidrug
      resistance-associated protein 2 (Mrp2), the main, multispecific transporter
      involved in the canalicular excretion of organic anions, was also decreased (
      40%), which was associated with a significant decrease in the cumulative biliary
      excretion of the Mrp2 substrate, dinitrophenyl-S-glutathione (-50%). These
      results show that chronic Al exposure leads to oxidative stress, cholestasis, and
      impairment of the hepatic handling of organic anions by decreasing both
      sinusoidal uptake and canalicular excretion. The alteration of the latter process
      seems to be causally related to impairment of Mrp2 expression. We have addressed
      some possible mechanisms involved in these deleterious effects.

PMID- 14976347
TI  - In utero and lactation exposure of rats to 1R4F reference cigarette mainstream
      smoke: effect on prenatal and postnatal development.
AB  - Childhood cognitive and behavioral deficits have been reported in children born
      to mothers who smoked during pregnancy (Institute of Medicine, 2001). To
      investigate these potential responses in an animal model, reproductive and
      neurotoxicity evaluations based on the U.S. FDA guidelines were used to examine
      the offspring of male and female Sprague-Dawley rats exposed 2 h/day, 7 days/week
      by nose-only inhalation to whole mainstream smoke total particulate matter (TPM).
      Concentrations of 150, 300, or 600 mg/m(3) were used (males: 4 weeks prior to and
      during mating; and females: 2 weeks prior to mating, during mating, and through
      weaning at postnatal day 21). Sham air controls receiving filtered air and cage
      controls were also maintained. F(1) rats were weighed, identified by gender,
      examined for clinical signs of toxicity, and evaluated for neurobehavioral
      effects through postnatal day 65. Parental exposure was evidenced by smoke
      concentration-related increases in blood carboxyhemoglobin, nicotine, and
      cotinine and by characteristic cigarette smoke-related rodent respiratory tract
      histopathology. Also, nicotine and cotinine were found in F(1) blood through the
      lactation period. Maternal toxicity occurred at concentrations of 300 and 600 mg
      TPM/m(3), where total body weight gain during gestation was significantly (p < or
      = 0.05) decreased compared to sham controls. While smoke concentration-related
      decreases in F(1) birth weight and growth were evident (600 mg TPM/m(3),
      significantly different from sham at all time points), no adverse effects on
      developmental landmarks, including age at vaginal patency or preputial
      separation, motor activity, acoustic startle response or learning, and memory,
      were observed in the F(1) generation. This study confirmed that maternal exposure
      to high levels of mainstream cigarette smoke during gestation and lactation
      reduces birth weight and retards growth in the rat neonate; however, the
      developmental and neurobehavioral testing methodologies employed did not appear
      to be sensitive for an evaluation of neonatal behavioral effects following
      parental smoke exposure.

PMID- 14976348
TI  - Prediction of torsade-causing potential of drugs by support vector machine
      approach.
AB  - In an effort to facilitate drug discovery, computational methods for facilitating
      the prediction of various adverse drug reactions (ADRs) have been developed. So
      far, attention has not been sufficiently paid to the development of methods for
      the prediction of serious ADRs that occur less frequently. Some of these ADRs,
      such as torsade de pointes (TdP), are important issues in the approval of drugs
      for certain diseases. Thus there is a need to develop tools for facilitating the
      prediction of these ADRs. This work explores the use of a statistical learning
      method, support vector machine (SVM), for TdP prediction. TdP involves multiple
      mechanisms and SVM is a method suitable for such a problem. Our SVM
      classification system used a set of linear solvation energy relationship (LSER)
      descriptors and was optimized by leave-one-out cross validation procedure. Its
      prediction accuracy was evaluated by using an independent set of agents and by
      comparison with results obtained from other commonly used classification methods
      using the same dataset and optimization procedure. The accuracies for the SVM
      prediction of TdP-causing agents and non-TdP-causing agents are 97.4 and 84.6%
      respectively; one is substantially improved against and the other is comparable
      to the results obtained by other classification methods useful for multiple
      mechanism prediction problems. This indicates the potential of SVM in
      facilitating the prediction of TdP-causing risk of small molecules and perhaps
      other ADRs that involve multiple mechanisms.

PMID- 14976349
TI  - Neurotoxicity produced by dibromoacetic acid in drinking water of rats.
AB  - An evaluation of potential adverse human health effects of disinfection
      byproducts requires study of both cancer and noncancer endpoints; however, no
      studies have evaluated the neurotoxic potential of a common haloacetic acid,
      dibromoacetic acid (DBA). This study characterized the neurotoxicity of DBA
      during 6-month exposure in the drinking water of rats. Adolescent male and female
      Fischer 344 rats were administered DBA at 0, 0.2, 0.6, and 1.5 g/l. On a
      mg/kg/day basis, the consumed dosages decreased greatly over the exposure period,
      with average intakes of 0, 20, 72, and 161 mg/kg/day. Weight gain was depressed
      in the high-concentration group, and concentration-related diarrhea and hair loss
      were observed early in exposure. Testing with a functional observational battery
      and motor activity took place before dosing and at 1, 2, 4, and 6 months. DBA
      produced concentration-related neuromuscular toxicity (mid and high
      concentrations) characterized by limb weakness, mild gait abnormalities, and
      hypotonia, as well as sensorimotor depression (all concentrations), with
      decreased responses to a tail-pinch and click. Other signs of toxicity at the
      highest concentration included decreased activity and chest clasping.
      Neurotoxicity was evident as early as one month, but did not progress with
      continued exposure. The major neuropathological finding was degeneration of
      spinal cord nerve fibers (mid and high concentrations). Cellular vacuolization in
      spinal cord gray matter (mostly) and in white matter (occasionally) tracts was
      also observed. No treatment-related changes were seen in brain, eyes, peripheral
      nerves, or peripheral ganglia. The lowest-observable effect level for
      neurobehavioral changes was 20 mg/kg/day (produced by 0.2 g/l, lowest
      concentration tested), whereas this dosage was a no-effect level for
      neuropathological changes. These studies suggest that neurotoxicity should be
      considered in the overall hazard evaluation of haloacetic acids.

PMID- 14976350
TI  - Alterations in gene expression induced in day-9 mouse embryos exposed to
      hyperthermia (HS) or 4-hydroperoxycyclophosphamide (4CP): analysis using cDNA
      microarrays.
AB  - Teratogen-induced alterations in gene expression play an important role in the
      genesis of malformations in animals. The recent development of DNA microarrays
      now offers the opportunity to monitor global changes in gene expression and
      therefore the potential to obtain significant new information concerning both
      normal and abnormal development. RNA was isolated from day-9 mouse embryos at 1
      and 5 h after exposure to hyperthermia (HS) or 4-hydroperoxycyclophosphamide
      (4CP) and compared to RNA isolated from concurrent controls using mouse cDNA
      microarrays. Cy5/Cy3 intensity data were extracted using Spot-on Image software
      and then normalized using the statistical software program R/maanova.
      Differentially expressed genes were identified using a linear mixed-effects model
      and p values derived from t-test statistics. Approximately 9000 genes show
      statistically significant alterations in expression in day-9 mouse embryos
      exposed to HS or 4CP. HS and 4CP also induce alterations in the expression of
      distinct sets of genes, e.g., DNA replication/repair, cell cycle, signal
      transduction, and transcription-related genes. As expected, a variety of heat
      shock genes are upregulated by HS but not 4CP. Among genes whose expression is
      altered by both HS and 4CP, cluster analysis identified three p53 target genes
      (Cyclin G1, Gtse1, and Mdm2), and follow up studies confirmed that p53 is
      activated in embryos exposed to these two teratogens. In addition, cluster
      analyses also revealed that HS but not 4CP induces the downregulation of genes
      encoding key enzymes in the cholesterol biosynthesis pathway. Thus, our
      microarray data have identified one potentially important pathway (p53) common to
      both HS- and 4CP-induced teratogenesis and another pathway (cholesterol
      biosynthesis) potentially important, but specific to HS-induced teratogenesis.

PMID- 14976351
TI  - Evaluation of xenobiotic N- and S-oxidation by variant flavin-containing
      monooxygenase 1 (FMO1) enzymes.
AB  - The flavin-containing monooxygenase gene family (FMO1-6) in humans encodes five
      functional isoforms that catalyze the monooxygenation of numerous N-, P- and S
      containing drugs and toxicants. A previous single nucleotide polymorphism (SNP)
      analysis of FMO1 in African-Americans identified seven novel SNPs. To determine
      the functional relevance of the coding FMO1 variants (H97Q, I303V, I303T, R502X),
      they were heterologously expressed using a baculovirus system. Catalytic
      efficiency and stereoselectivity of N- and S-oxygenation was determined in the
      FMO1 variants using several substrates. The I303V variant showed catalytic
      constants equal to wild-type FMO1 for methimazole and methyl p-tolyl sulfide.
      Catalytic efficiency (V(max)/K(m)) of methyl p-tolyl sulfide oxidation by R502X
      was unaltered. In contrast, methimazole oxidation by R502X was not detected. Both
      H97Q and I303T had elevated catalytic efficiency with regards to methyl p-tolyl
      sulfide (162% and 212%, respectively), but slightly reduced efficiency with
      regards to methimazole (81% and 78%). All the variants demonstrated the same
      stereoselectivity for methyl p-tolyl sulfide oxidation as wild-type FMO1. FMO1
      also metabolized the commonly used insecticide fenthion to its (+)-sulfoxide,
      with relatively high catalytic efficiency. FMO3 metabolized fenthion to its
      sulfoxide at a lower catalytic efficiency than FMO1 (27%) and with less
      stereoselectivity (74% (+)-sulfoxide). Racemic fenthion sulfoxide was a weaker
      inhibitor of acetylcholinesterase than its parent compound (IC(50) 0.26 and 0.015
      mM, respectively). The (+)- and (-)-sulfoxides were equally potent inhibitors of
      acetylcholinesterase. These data indicate that all the currently known FMO1
      variants are catalytically active, but alterations in kinetic parameters were
      observed.

PMID- 14976352
TI  - Role of mitochondrial dysfunction in combined bile acid-induced cytotoxicity: the
      switch between apoptosis and necrosis.
AB  - The goal of this investigation was to determine whether chenodeoxycholic acid
      (CDCA)-induced apoptosis is prevented by ursodeoxycholic acid (UDCA) or
      tauroursodeoxycholic acid (TUDC) and to characterize the involvement of
      mitochondria in the process. Cultured human HepG2 cells were treated in a dose-
      and time-dependent protocol in order to establish a sufficiently low exposure to
      CDCA that causes apoptosis but not necrosis. Low-dose CDCA induced an S-phase
      block and G2 arrest of the cell cycle, as determined by flow cytometry. As a
      result, cell proliferation was inhibited. CDCA-induced apoptosis, as determined
      by fluorescence microscopy of Hoechst 33342-stained nuclei, was evident upon
      coincubation with TUDC. Additionally, after exposure to UDCA plus CDCA, the cell
      membrane was permeable to fluorescent dyes. Caspase-9-like activity, poly(ADP
      ribose) polymerase (PARP) cleavage, and extensive DNA fragmentation were detected
      in CDCA-exposed cells and in cells coincubated with TUDC, but not UDCA. CDCA
      caused a decrease in mitochondrial membrane potential and depletion of ATP, both
      of which were potentiated by UDCA but not TUDC. The results suggest that UDCA
      potentiates CDCA cytotoxicity, probably at the level of induction of the
      mitochondrial permeability transition (MPT). Consequently, as suggested by the
      lack of the main hallmarks of the apoptotic pathway, in the presence of UDCA,
      CDCA-induced apoptosis is not properly executed but degenerates into necrosis.

PMID- 14976353
TI  - Single cell analysis of switch-like induction of CYP1A1 in liver cell lines.
AB  - The shape of the dose-response curve may vary depending on whether one examines
      response at a population or a single cell level. Populations of cells may exhibit
      a graded response whereas single cell responses may have threshold or switch-like
      behavior. Studies in vivo and in vitro using primary hepatocyte cultures have
      shown that induction of CYP1A1 in the liver exhibits switch-like behavior in
      response to PCB 126 (3,3',4,4',5-pentachlorobiphenyl). The goal of the present
      study was to determine if two liver cell lines (H4IIE rat hepatoma and Hepa 1c1c7
      mouse hepatoma) also show switch-like behavior and develop experimental models
      for studying mechanisms of these switch-like responses. Both cell lines were
      analyzed via concentration-response and time-course studies using quantitative
      real-time PCR, revealing a sigmoidal concentration-response curve for CYP1A1 mRNA
      induction at the population level. To study CYP1A1 protein induction on a single
      cell level, flow cytometry was employed. In both cell lines the distribution of
      fluorescence increased with increasing concentrations of PCB 126. The switch
      behavior was more pronounced in the H4IIE cells than in the Hepa 1c1c7 cells,
      exhibiting a well-defined shift of induction from the "off" to the "on" state.
      The concentration-response curve at the single cell level appeared more switch
      like with two populations of cells-basal levels and maximally induced.
      Immunocytochemistry studies of individual cells also support these conclusions.
      Our data support the hypothesis that PCB 126 induces CYP1A1 in a switch-like
      fashion in H4IIE rat hepatoma cells. These cells can now be used to study the
      mechanism of the biological switch.

PMID- 14976354
TI  - Interactive effects of paraoxon and pyridostigmine on blood-brain barrier
      integrity and cholinergic toxicity.
AB  - The effect of the organophosphorous insecticide paraoxon on the integrity of the
      blood-brain barrier (BBB) and permeability of pyridostigmine (PYR), a peripheral
      inhibitor of cholinesterase activity, was examined in Long Evans rats. The
      integrity of the BBB was examined by measuring the number of capillaries leaking
      horseradish peroxidase, which was injected into the heart. Treatment with
      paraoxon at 100 microg/kg, intramuscularly, resulted in a 3- to 4-fold increase
      in the number of leaky capillaries in young rats (25 to 30 days old) but not in
      older rats (90 days old). Interestingly, young rats treated with PYR (30 mg/kg,
      po) 50 min before treatment with paraoxon showed an inhibited effect of paraoxon
      on the BBB. Furthermore, no increase in the degree of inhibition of
      acetylcholinesterase activity was observed in young rats treated with PYR before
      paraoxon compared with young rats treated with paraoxon alone. Cholinergic
      toxicity, as assessed by changes in behavior, was not observed in young rats
      treated with paraoxon alone; but, slight signs of cholinergic toxicity were
      observed in rats treated with PYR. Young rats treated with both PYR and paraoxon
      did not exhibit more extensive signs of toxicity than rats treated with paraoxon
      alone or PYR alone. The results indicate that treatment with paraoxon can
      compromise BBB permeability at dosages that do not induce cholinergic toxicity,
      but only in young rats. Also, PYR pre-exposure appears to protect the BBB from
      the paraoxon-induced alterations.

PMID- 14976355
TI  - Workshop overview: Hepatotoxicity assessment for botanical dietary supplements.
AB  - Botanical dietary supplements (herbal products) have flooded the market in the
      United States over the past decade, and studies show a significant percentage of
      Americans use them. With increasing frequency and duration of exposure, some
      serious adverse effects, though relatively uncommon, have been reported. Among
      the most troublesome is the association of some botanicals with serious
      hepatotoxicity. In some cases, hepatotoxicity has been linked to the consumption
      of botanicals with recognized hepatotoxic components (e.g., pyrrolizidine
      alkaloids). However, in other cases, the causative agent(s) is less clear and,
      overall, the mechanisms of hepatotoxicity are poorly understood. To help create a
      scientific basis for understanding botanical-induced hepatotoxicity and better
      tools for hepatotoxicity assessment and prediction, the National Center for
      Natural Product Research (NCNPR) hosted a workshop (September 8 and 9, 2003) in
      cooperation with the Center for Food Safety and Applied Nutrition (CFSAN) of the
      Food and Drug Administration (FDA). The workshop featured presentations by 22
      experts and was attended by 65 individuals. The agenda can be found in the
      supplementary data at www.toxsci.oupjournals.org.

PMID- 14976356
TI  - Evaluation of the use of reporter antigens in an auricular lymph node assay to
      assess the immunosensitizing potential of drugs.
AB  - Immune-mediated idiosyncratic drug reactions are a major problem for susceptible
      patients, physicians, and the pharmaceutical industry. Validated screening tools
      to assess the immunosensitizing capacity of orally or intravenously administered
      pharmaceuticals are currently not available. To date, the popliteal lymph node
      assay (PLNA) seems the most promising tool for this purpose. The PLNA has
      recently been extended with the use of reporter antigens (RA) that are coinjected
      together with the drug of interest. The measurement of isotypes of RA-specific
      antibody-secreting cells (ASC) enables the distinction of sensitizing chemicals
      and (nonsensitizing) irritants without radio-isotopic end points. However, the
      use of footpad injections raises ethical concerns. Therefore, we examined the use
      of RA after intradermal injection into the ear of BALB/c mice and measured RA
      specific ASC in the draining auricular lymph node (ALN). We show that RA-specific
      IgG isotype ASC numbers are very useful and sensitive parameters to identify drug
      induced hypersensitivity in both PLN and ALN. However, the type 1-associated
      parameters (CD8(+) cells, macrophages, IFN-gamma, TNF-alpha, and IL-1 beta) that
      are induced in the PLN by streptozotocin were less pronounced in the ALN. Thus,
      the PLNA may provide more immunologically relevant information on the mechanisms
      of certain chemical-induced hypersensitivity reactions. The RA-ALN assay may
      provide an alternative for the RA-PLNA; both assays can be used to distinguish
      sensitizing compounds from nonsensitizing ones.

PMID- 14976357
TI  - Characterization of the species-specificity of peroxisome proliferators in rat
      and human hepatocytes.
AB  - Peroxisome proliferation is a well-defined pleiotropic effect that is mediated by
      the ligand inducible transcription factor peroxisome proliferator-activated
      receptor (PPAR) alpha. Because marked peroxisome proliferation occurs in rodents
      but not in humans, we aimed to elucidate the molecular and cellular determinants
      of this species-specificity in hepatocytes. Analysis of peroxisomal marker enzyme
      activities confirmed that peroxisome proliferators induced acyl-CoA oxidase
      (ACOX) and to a lesser extent catalase in rat hepatocytes, but not in human
      hepatoma HepG2 cells. Transient transfection assays revealed that ciprofibrate
      and Wy 14,643 induced rat but not human PPARalpha-mediated reporter gene activity
      in rat FAO and primary hepatocytes on rat but not on human PPARalpha response
      elements (PPREs). In contrast, in human HepG2 and primary human hepatocytes,
      peroxisome proliferators did not induce either human or rat PPARalpha activity
      regardless of rat or human PPRE sequences. In addition, no induction of ACOX gene
      expression was observed in human hepatocytes independent of the expression level
      of human PPARalpha. Remarkably, no distinct peroxisome proliferation related
      responses were observed in human hepatocytes when rat PPARalpha was transfected,
      although human hepatocytes were responsive to PPARalpha-mediated induction of
      carnitine palmitoyl transferase-1A and 3-hydroxy-3-methylglutaryl-CoA synthase.
      These results confirmed that PPARalpha and PPREs are important determinants for
      the species-specificity of peroxisome proliferation. Nevertheless, our results
      showed that human hepatocytes limit the extent of peroxisome proliferation
      regardless of PPARalpha expression.

PMID- 14976358
TI  - Flow cytometry: an introduction.
AB  - A flow cytometer is an instrument that illuminates cells (or other particles) as
      they flow individually in front of a light source and then detects and correlates
      the signals from those cells that result from the illumination. In this chapter,
      each of the aspects of that definition will be described: the characteristics of
      cells suitable for flow cytometry, methods to illuminate cells, the use of
      fluidics to guide the cells individually past the illuminating beam, the types of
      signals emitted by the cells and the detection of those signals, the conversion
      of light signals to digital data, and the use of computers to correlate and
      analyze the data after they are stored in a data file. The final section of the
      chapter will discuss the use of a flow cytometer to sort cells. This chapter can
      be read as a brief, self-contained survey. It can also be read as a gateway with
      signposts into the field. Other chapters in this book will provide more details,
      more references, and even some controversy about specific topics.

PMID- 14976359
TI  - Multiparameter flow cytometry of bacteria.
AB  - The small size of bacteria makes some microbial constituents undetectable or
      measurable with only limited precision by flow cytometry. Bacteria may also
      behave differently from eukaryotes in terms of their interaction with dyes,
      drugs, and other reagents. It is therefore difficult to design multiparameter
      staining protocols that work, unmodified, across a wide range of bacterial
      species. This chapter describes reliable flow cytometric methods for assessment
      of the physiologic states of Gram-negative organisms, on the one hand, and Gram
      positive organisms, on the other, based on measurement of membrane potential and
      membrane permeability. These techniques are useful in the assessment of effects
      of environmental conditions and antimicrobial agents on microorganisms.

PMID- 14976360
TI  - Multiparameter data acquisition and analysis of leukocytes.
AB  - For data acquisition, each supplier provides the software necessary and unique to
      its instrument. For data analysis, the same software may be used. In addition,
      several second party vendors provide software often with more capabilities than
      that provided by the instrument companies. Because of the increase in
      multiparameter data acquisition, we describe one method for validating instrument
      performance prior to data acquisition. The fundamentals of data analysis leading
      to a generic strategy for analysis of any number of parameters are described.
      This generic approach is designed to simplify the increasing complexity of
      multiparameter data analysis.

PMID- 14976361
TI  - Flow cytometric analysis of kinase signaling cascades.
AB  - Flow cytometry offers the capability to assess the heterogeneity of cellular
      subsets that exist in complex populations, such as peripheral blood, based on
      immunophenotypes. We describe methodologies to measure phospho-epitopes in single
      cells as determinants of intracellular kinase activity. Multiparametric staining,
      using both surface and intracellular stains, allows for the study of discrete
      biochemical events in readily discernible lymphocyte subsets. As such, the usage
      of multiparameter flow cytometry to obtain proteomic information provides several
      major advantages: (1) the ability to perform multiparametric experiments to
      identify distinct signaling profiles in defined lymphocyte populations, (2)
      simultaneous correlation of multiple active kinases involved in signaling
      cascades, (3) profiling of active kinase states to identify signaling signatures
      of interest rapidly, and (4) biochemical access to rare cell subsets such as
      those from clinically derived samples or populations that comprise too few in
      numbers for conventional biochemical analysis.

PMID- 14976362
TI  - Cytokine flow cytometry.
AB  - Cytokine flow cytometry (CFC) is a general term that applies to flow cytometric
      analysis of cells using anticytokine antibodies as markers of activation. The
      most common version of this technique is the intracellular staining of cytokines
      in cells that have been fixed and permeabilized after short-term in vitro
      activation. When used with specific antigens, this technique allows for the
      quantitation of rare populations of antigen-specific T cells. In this chapter,
      specific methodology for such intracellular staining is elaborated, with emphasis
      on the effects of variables such as sample type, antigens, activation conditions,
      sample processing, and data acquisition and analysis.

PMID- 14976363
TI  - Use of cell-tracking dyes to determine proliferation precursor frequencies of
      antigen-specific T cells.
AB  - The T-cell receptor provides T cells with specificity for antigens of particular
      molecular structure (the "epitope"); the T-cell pool in an individual responds to
      the presence of many different antigenic epitopes, but any particular T cell will
      respond preferentially to one defined epitope. After stimulation of a T cell by
      the binding of its receptor to its cognate antigen in the context of a major
      histocompatibility complex (MHC) molecule on an antigen-presenting cell, the T
      cell will begin to proliferate and synthesize cytokines. Tetramer binding and the
      enzyme-linked immunospot (ELISPOT) method have been used to determine what
      proportion of cells in the T-cell pool can bind to a defined antigenic peptide or
      will secrete cytokines in response to a particular antigenic stimulation. The
      method described here uses tracking dyes to determine what proportion of T cells
      will proliferate in response to stimulation. As a flow cytometric "single-cell"
      method, it can be combined with tetramer and cytokine staining to determine the
      precursor frequencies of cells in the T-cell pool able to bind tetramer, to
      synthesize cytokines, and to proliferate in response to antigen.

PMID- 14976364
TI  - Assessment of lymphocyte-mediated cytotoxicity using flow cytometry.
AB  - Cytotoxic lymphocytes, including cytotoxic T lymphocytes (CTLs) and natural
      killer (NK) cells, kill target cells by releasing granules containing perforin
      and granzymes, and/or via Fas-Fas ligand interactions. Both pathways lead to
      prompt activation within target cells of caspase cascades responsible for
      apoptosis induction and cell death. We have utilized cell-permeable fluorogenic
      caspase substrates and multiparameter flow cytometry to detect caspase activation
      in target cells, and applied these tools to quantify and visualize cytotoxic
      lymphocyte activities. This novel assay, referred to as the flow cytometric
      cytotoxicity (FCC) assay, is a nonradioactive single-cell-based assay that
      provides a more rapid, biologically informative, and sensitive approach to
      measure cytotoxic lymphocyte activity when compared to other assays such as the
      51chromium (51Cr) release assay. In addition, the FCC assay can be used to study
      CTL-mediated killing of primary target cells of different cell lineages that are
      frequently not amenable to study by the 51Cr release assay. Furthermore, the FCC
      assay enables evaluation of the phenotype and fate of both target and effector
      cells, and as such, provides a useful new approach to illuminate the biology of
      cytotoxic lymphocytes.

PMID- 14976365
TI  - Multiparametric analysis of apoptosis by flow and image cytometry.
AB  - Flow cytometric assays for apoptosis are now in widespread use. The
      multiparametric nature of flow cytometry allows multiple assays for several
      apoptotic characteristics to be combined in a single sample, providing a powerful
      tool for elucidating the complex progression of apoptotic death in a variety of
      cell types. This chapter describes one such assay, allowing simultaneous analysis
      of caspase activation, annexin V binding to "flipped" phosphatidylserine residues
      and membrane permeability to DNA binding dyes. This multidimensional approach to
      analyzing apoptosis provides far more information than single-parameter assays
      that provide only an ambiguous "percent apoptotic" result, given that multiple
      early, intermediate, and late apoptotic stages can be visualized simultaneously.
      This multiparametric approach is also amenable to a variety of flow cytometric
      instrumentation, both old and new.

PMID- 14976366
TI  - Detection and enrichment of hematopoietic stem cells by side population
      phenotype.
AB  - A flow cytometric procedure has recently been described to isolate hematopoietic
      stem cells from mouse bone marrow based on the efflux properties of the vital dye
      Hoechst 33342. The assay defines a subset of cells-termed the "side population"
      (SP)-by simultaneously measuring fluorescence of the dye at two wavelengths (~450
      nm and >670 nm). In this chapter, SP protocols are provided to detect candidate
      hematopoietic stem cells in mouse bone marrow and human cord blood. In the
      standard method, SP profiles are readily observed on a stream-in-air cell sorter
      using 30 mW of 351-356 nm ultraviolet excitation from a krypton-ion laser.
      Alternatively, SP profiles can be resolved on an analytical flow cytometer with
      cuvette flow cell using 8 mW of 325-nm ultraviolet excitation from a helium
      cadmium laser. The ability to perform the SP assay on an analytical instrument
      facilitates optimization of staining conditions to identify hematopoietic and
      other stem cells in a variety of tissues. It is also demonstrated that SP
      profiles of slightly lower resolution can be obtained on a stream-in-air cell
      sorter using 100 mW of 407-nm violet excitation from a krypton-ion laser, raising
      the possibility that with appropriate validation the SP assay could be performed
      on flow cytometers that are not equipped with ultraviolet lasers.

PMID- 14976367
TI  - Hematopoietic stem cell characterization by Hoechst 33342 and rhodamine 123
      staining.
AB  - A dual-dye efflux strategy utilizing the supravital dyes Hoechst 33342 (Ho) and
      rhodamine 123 (Rh123) is described and illustrated for the detection and analysis
      of hematopoietic stem cells in murine bone marrow. Mononuclear cells from bone
      marrow cell suspensions were incubated in a cocktail of Rh123 plus Ho, and both
      dyes were effluxed by two 15-min incubations in dye-free buffer prior to sorting.
      Compared to our original prototype method in which Rh123, but not Ho, was
      effluxed, this dual-dye efflux protocol more rapidly and efficiently resolves the
      most primitive Hodull/Rhdull hematopoietic stem cells. Moreover, under conditions
      of optimal dual-dye uptake and efflux, Hodull/Rhdull cells map to the subfraction
      of side population (SP) cells with the highest efflux of Ho, which were
      previously demonstrated to possess the highest hematopoietic stem cell activity.

PMID- 14976368
TI  - Phenotypic and functional analyses of CD34NEG hematopoietic precursors from
      mobilized peripheral blood.
AB  - Methods are described for the characterization of CD34 antigen modulation and its
      relationship to cell proliferation in early human hematopoietic cells. Toward
      that end, quiescent primitive CD34+ and CD34NEG cells are purified from mobilized
      peripheral blood (MoPB). Unlike CD34NEG cells from other sources, those from MoPB
      grow readily in stroma-free culture, facilitating their analysis. Using a lineage
      depleted, low-density mononuclear cell fraction, CD34NEGCD38NEGLINNEG and
      CD34+CD38NEGLINNEG cells are purified by cell sorting. Cells are cultured in
      serum-free medium supplemented with early acting cytokines. Up- and
      downmodulation of CD34 antigen can be observed within 40 h of incubation. Samples
      are removed for analysis of expression of CD34, CD38 and lineage-commitment
      antigens as well as for cell proliferation as determined by expression of Ki67
      antigen and uptake of pyronin Y. This approach permits an assessment of changes
      in CD34 and CD38 antigen expression by primitive LINNEG cells as they are
      activated for growth or remain in a quiescent state.

PMID- 14976369
TI  - Multiparameter flow cytometry of fluorescent protein reporters.
AB  - Reporters based on the green fluorescent protein (GFP) from the jellyfish
      Aequorea victoria and GFP-like proteins from other marine organisms provide
      valuable tools to monitor gene transfer and expression noninvasively in living
      cells. Stable cell lines were generated from the Sp2/0-Ag14 hybridoma that
      express up to three spectral enhanced versions of GFP, the enhanced cyan
      fluorescent protein (ECFP), the enhanced green fluorescent protein (EGFP), and
      the enhanced yellow fluorescent protein (EYFP), and/or a variant of the Discosoma
      coral red fluorescent protein (DsRed). The panel of lines was used to demonstrate
      a flow cytometric procedure for simultaneous analysis of all four fluorescent
      proteins that utilizes dual-laser excitation at 488 nm and 407 nm. Additional
      schemes for simultaneous detection of two, three or four of these fluorescent
      proteins are also presented.

PMID- 14976370
TI  - Analysis of fluorescent protein expressing cells by flow cytometry.
AB  - The process for transfection of cells with expression and gene-trap vectors
      expressing fluorescent reporter proteins is described. The measurement and
      sorting of discrete populations of transfected cells is also described and
      illustrated. Of particular importance, the maintenance of stability may be
      important and a simple strategy to monitor this has been developed. Finally, an
      effective method for improving the ability to measure low-level fluorescence from
      autofluorescence is described.

PMID- 14976371
TI  - Integrative flow cytometric and microarray approaches for use in transcriptional
      profiling.
AB  - Flow cytometry and cell sorting provides unparalleled means for the
      identification and purification of specific cell types. It is a mature technology
      having been in existence commercially for the last 25 yr. High-throughput
      transcriptional profiling methods have emerged relatively recently. These provide
      the means to characterize efficiently the genome-wide contribution of individual
      genes to gene expression. A combination of these methods offers the opportunity
      to explore the relationship between gene expression and the ways in which
      different cell types are formed and maintained. This chapter provides a review of
      published methods for analysis of global gene expression within different cell
      types in complex tissues and organs, and provides practical details concerning
      microarray fabrication and use based on presynthesized 70-mer oligonucleotide
      array elements.

PMID- 14976372
TI  - Flow cytometric analysis of fluorescence resonance energy transfer: a tool for
      high-throughput screening of molecular interactions in living cells.
AB  - The study of cellular processes has been facilitated by the use of methods to
      detect molecular associations both in vivo and in vitro. An invaluable tool to
      study molecular associations associated with dynamic processes in living cells
      utilizes the phenomenon of fluorescence resonance energy transfer (FRET),
      together with selected fluorophores that are attached to molecules of interest.
      Many reports have utilized fluorophores conjugated to antibodies for FRET pairs.
      However, these methods are restricted to extracellular molecules and dependent
      upon the availability of appropriate antibodies. The recent development of green
      fluorescent protein (GFP) variants suitable for FRET has expanded the utility of
      this methodology by permitting the study of intracellular as well as
      extracellular processes. Combining FRET with flow cytometric analysis results in
      a powerful high-throughput assay for molecular associations. This article details
      the use of green fluorescent protein (GFP) mutants cyan fluorescent protein (CFP)
      and yellow fluorescent protein (YFP) to measure the association of the signaling
      component TRAF2 with the TNFR-2 receptor to illustrate the versatility of this
      methodology.

PMID- 14976373
TI  - Design of a fluorescence-activated cell sorting-based Mammalian protein-protein
      interaction trap.
AB  - The mammalian protein-protein interaction trap (MAPPIT) is a two-hybrid assay
      based on insights in type I cytokine signal transduction. Bait and prey
      polypeptides are tethered to mutant cytokine receptor chimeras which are impaired
      in signaling. On bait-prey interaction and after ligand stimulation, the JAK-STAT
      signaling cascade is initiated leading to transcription of a reporter or marker
      gene under the control of the STAT3-responsive rPAP1 promoter. In addition to a
      physiologically relevant context for mammalian protein-protein interactions this
      method provides separation of interactor and effector zones, and can be applied
      for both analytical and screening purposes. In the protocol described here, a
      cytokine receptor derived surface tag is used as a selectable marker. After an
      initial presort step using magnetic-activated cell sorting (MACS), "positive"
      cells are selected by fluorescence-activated cell sorting (FACS).

PMID- 14976374
TI  - Flow cytometric screening of yeast surface display libraries.
AB  - A method to screen and isolate antigen specific clones from a library of single
      chain antibodies expressed on the surface of yeast cells is presented. Two rounds
      of magnetic bead enrichment before flow cytometric sorting enables one to screen
      libraries of far greater diversity than can be screened by just flow cytometry.
      The strength of flow cytometric sorting is the ability to follow the selection in
      real time and to isolate easily the highest affinity antigen-specific clones. A
      major strength of yeast display as a discovery platform is the ability to
      characterize the binding properties, the affinity of a clone without the need for
      subcloning, expression, and purification of the scFv. The methodology for
      directed evolution of single-chain antibodies to increase the affinity of a clone
      is also described.

PMID- 14976375
TI  - Fluorescence resonance energy transfer-based HIV-1 virion fusion assay.
AB  - The fluorescence resonance energy transfer (FRET)-based HIV-1 virion fusion assay
      exploits the incorporation of beta-lactamase-Vpr chimeric proteins into HIV-1
      virions and their subsequent delivery into the cytoplasm of target cells as a
      marker of fusion. This transfer can be monitored by the enzymatic cleavage of the
      CCF2-AM dye, a fluorescent substrate of beta-lactamase (BlaM), loaded into the
      target cells. BlaM cleavage of the beta-lactam ring in CCF2-AM prevents the FRET
      between the coumarin and fluorescein moieties of the dye. This cleavage changes
      the fluorescence emission spectrum of CCF2-AM from green (520 nm) to blue (447
      nm), and thus permits detection of fusion by fluorescence microscopy, flow
      cytometry, or UV photometry. This assay is simple and rapid to perform, and
      exhibits high sensitivity and specificity. Importantly, it can be applied to
      study HIV-1 virion fusion in primary cells and can be combined with
      immunostaining for subset discrimination in heterogeneous target cell
      populations. Finally, the assay can also be adapted to study fusion mediated by
      the envelope proteins from other viruses through the construction of HIV-1
      pseudotypes.

PMID- 14976376
TI  - Cell-cycle analysis of asynchronous populations.
AB  - Cells are incubated continuously in bromodeoxyuridine (BrdUrd), which is
      incorporated into cells synthesizing DNA. At intervals, cells are harvested and
      nuclei are prepared and stained with a bis-benzimidazole, Hoechst 33258, and
      propidium iodide. In the flow cytometer, the dyes are excited by UV and blue and
      red fluorescences recorded. BrdUrd quenches the blue fluorescence of the Hoechst
      dye. The degree of quenching records the progress of the cell through S phase(s);
      the red (PI) fluorescence yields the cell cycle phases. By this means, the
      progress of cells around the cell cycle can be followed and the effects of
      cytotoxic drugs, radiation, and other treatments observed.

PMID- 14976377
TI  - Solid tumor DNA content analysis.
AB  - Flow cytometric DNA content analysis provides a rapid and reliable analysis of
      DNA ploidy and the proliferative fraction of tumor specimens. Both archival and
      fresh specimens are suitable for this technique. This information can be used in
      conjunction with traditional prognostic factors in the biological assessment of
      certain carcinomas. Among these tumors are early stages of breast, colon, lung,
      and bladder carcinomas.

PMID- 14976378
TI  - Concurrent flow cytometric analysis of DNA and RNA.
AB  - Concurrent analysis of DNA and RNA by flow cytometry provides information on the
      DNA content and the transcriptional status of cells. This can be accomplished
      using metachromatic fluorochromes that bind to DNA by intercalation and to single
      stranded RNA electrostatically. Because cell viability is a prerequisite for the
      analysis, freshly prepared cells must be used. Simultaneous DNA/RNA analysis can
      be used primarily in the classifications and biological assessment of
      hematoreticular malignancies including multiple myeloma.

PMID- 14976379
TI  - Telomere length measurement by fluorescence in situ hybridization and flow
      cytometry.
AB  - Telomere length is an important measure of cellular differentiation and
      progression to senescence. Flow cytometric assays for measuring telomere length
      have become an important adjunct to more laborious Southern blotting methods;
      telomere length can be estimated with considerable accuracy in small numbers of
      individual cells by flow cytometry, and can be measured in cell population
      subsets with simultaneous fluorescent immunophenotyping. In this chapter, we
      describe the standard flow cytometric assay for measuring telomere length,
      including the incorporation of fluorochrome-conjugated antibody immunolabeling
      for measurement in cell subsets.

PMID- 14976380
TI  - Small lasers in flow cytometry.
AB  - Laser technology has made tremendous advances in recent years, particularly in
      the area of diode and diode-pumped solid state sources. Flow cytometry has been a
      direct beneficiary of these advances, as these small, low-maintenance,
      inexpensive lasers with reasonable power outputs are integrated into flow
      cytometers. In this chapter we review the contribution and potential of solid
      state lasers to flow cytometry, and show several examples of these novel sources
      integrated into production flow cytometers. Technical details and critical
      parameters for successful application of these lasers for biomedical analysis are
      reviewed.

PMID- 14976381
TI  - Viable infectious cell sorting in a BSL-3 facility.
AB  - With the increase in demand for high-speed cell sorting of viable infectious and
      now therapeutic cell samples, safety concerns for the protection of flow
      cytometer operators have increased. This chapter describes a quick, sensitive,
      and reproducible procedure to assure sample containment before sorting these
      samples. This procedure includes aerosol containment, physical barriers,
      environmental controls, and personal protection. An aerosol management system
      produces a negative pressure within the sort chamber where aerosols are vacuumed
      directly into a HEPA filter. Physical barriers include the manufacturer's
      standard plastic shield and panels. The flow cytometer is contained in a BSL-3
      laboratory for maximum environmental control and the operator is protected using
      a respiratory system. Containment is measured using highly fluorescent Glo-Germ
      particles under the same conditions as the cell sort but with the sorter adjusted
      to produce large amounts of aerosols. These aerosols are collected by a vacuum
      air sampling system for 10 min in three locations onto a glass slide and examined
      microscopically. With this system in place, aerosol containment can be measured
      quickly and efficiently, therefore reducing the risk to the operator when sorting
      viable infectious cells.

PMID- 14976382
TI  - Stratum corneum maturation. A review of neonatal skin function.
AB  - The importance of the stratum corneum and its barrier function for infants,
      especially for newborns, is clinically evident. Research regarding the maturation
      of the stratum corneum in neonates, i.e. when full barrier function is obtained,
      has produced varying results. Based on transepidermal water loss and percutaneous
      absorption studies, term infants seem to possess stratum corneum with adult
      barrier properties. Additionally, postnatal life is thought to accelerate stratum
      corneum maturation, so that even preterm infants have barrier function similar to
      term infants at 2-3 weeks of gestational age. However, a look at other
      parameters, such as skin thickness, skin pH and stratum corneum hydration, shows
      that neonatal skin is always adjusting to the extrauterine environment in
      contrast to the steady state of adult skin. This suggests that barrier
      stabilization may be dependent on achieving a balance between different
      parameters. However, it is still in question, which parameters, what balance and
      what timing. This paper provides an up-to-date overview on the neonatal skin
      barrier based on the review of current literature.

PMID- 14976383
TI  - Actinic keratosis: the key event in the evolution from photoaged skin to squamous
      cell carcinoma. Therapy based on pathogenetic and clinical aspects.
AB  - Skin aging is the result of intrinsic and extrinsic factors. Extrinsic aging,
      also called photoaging, is mainly caused by ultraviolet radiation from the sun
      and leads to a state which has been termed dermatoheliosis. The aim of this
      article is to provide an overview of photoaged skin addressing actinic keratoses
      (AKs) in particular. This review will describe the clinical features of photoaged
      skin and briefly summarize the underlying histological, photobiochemical and
      molecular mechanisms responsible for photoaging. The concept of the disease
      continuum from AK to squamous cell carcinoma will also be presented. A special
      focus will be on established and new therapeutic approaches to undo photoinduced
      skin damage.

PMID- 14976384
TI  - Synergistic effect of N-acetylglucosamine and retinoids on hyaluronan production
      in human keratinocytes.
AB  - Hyaluronan (HA) is well known to reside in the extracellular matrix as a water
      sorbed macromolecule. The aims of this study were twofold: to investigate the
      regulation of HA synthesis in keratinocytes, and to develop a method to modulate
      this regulatory process. We found that N-acetylglucosamine (NAG) increased the
      production of HA by cultured keratinocytes dose dependently, but had no effect on
      the production by skin fibroblasts. The effect of NAG in keratinocytes was found
      to be specific for HA production, as there was no change in sulfated
      glycosaminoglycan formation. The copresence of NAG with either of two retinoids,
      retinoic acid (RA) or retinol, exerted a synergistic effect on HA production. To
      investigate whether human HA synthase (HAS) genes were regulated by NAG or
      retinoids, total RNA extracted from cells treated with these agents was subjected
      to Northern blot analysis. We observed that RA and retinol markedly induced the
      expression of HA synthase-3 (HAS3) mRNA. Moreover, beta-carotene, a provitamin A,
      influenced HA production and HAS3 gene expression in a manner similar to the
      retinoids. Conversely, NAG had no effect on the expression of HAS3 transcripts.
      Pretreatment of cells with RA stimulated the activity of membrane-associated HAS,
      whereas pretreatment with NAG did not. These results suggest that HA production
      is regulated by at least two pathways: one involving the regulation of HAS gene
      expression, and the other independent of such a regulatory effect. Taken
      together, our findings suggest that NAG is a new modulator of HA synthesis.

PMID- 14976385
TI  - Lateral diffusion of ibuprofen in human skin during permeation studies.
AB  - In order to characterize the quality of dermal preparations, permeation studies
      using human stratum corneum or artificial skin constructs are carried out. For a
      better understanding of the diffusion processes a method to measure the lateral
      diffusion in skin samples was developed allowing an estimation of built-up drug
      depots. By extracting concentric skin segments surrounding the site of
      application, lateral drug diffusion was determined. Both, excised human skin and
      artificial skin constructs, showed comparable results with two phases of lateral
      diffusion (accumulation/redistribution). The use of permeation enhancers promoted
      lateral diffusion and thus increased the tendency to create a drug depot within
      the skin.

PMID- 14976386
TI  - Dithranol in an emulsifying oil base (bio-wash-oil) for the treatment of
      psoriasis of the scalp.
AB  - On the scalp, dithranol has been studied in only a few trials. The dithranol
      molecule that contains both hydrophilic and lipophilic centers can be
      incorporated into detergents and allows easy removal from hair. This property has
      led to the incorporation of dithranol in an emulsifying oil base (bio-wash-oil).
      The formulation has been used routinely for more than two decades in East
      Germany. We reexamined the efficacy and safety of dithranol in bio-wash-oil and
      compared it to dithranol embedded in crystalline monoglycerides (Micanol) in
      patients with psoriasis of the scalp. In a prospective, parallel group study, 64
      patients attending a day-care clinic were randomly allocated to 3 treatment
      groups: (1) dithranol in bio-wash-oil; (2) Micanol cream, and (3) Micanol cream
      in bio-wash-oil. Treatment was carried out for 3 weeks and results assessed using
      a modified Psoriasis Area and Severity Index score. Dithranol in bio-wash-oil
      resulted in a reduction in the score of 34% on day 7 and 57% on day 14. This was
      significantly better than in groups 2 and 3, as were the overall response and
      patients' assessment at the end of treatment (p < 0.05). Dithranol in a bio-wash
      oil is an effective, well-tolerated and low-priced treatment in psoriasis of the
      scalp.

PMID- 14976387
TI  - EEMCO guidance for the assessment of hair shedding and alopecia.
AB  - Knowledge of the hair follicle anatomy and the dynamics of hair cycling is
      substantial. Recognizing the anagen, catagen and telogen phases as well as
      teloptosis and the hair eclipse phenomenon clearly characterizes the typical hair
      chronobiology. Physiological modulators include hormones, neuromediators,
      miscellaneous biomolecules, seasons, micro-inflammation and ageing. For
      individuals who present with the complaint of increased hair shedding or
      alopecia, a host of evaluation techniques are available in addition to history,
      physical examination and laboratory assessment. Various clinical hair techniques
      can help in assessing the efficacy of drugs and cosmetics on hair growth. The
      methods are quite similar to those used to establish a definite diagnosis in
      dermatological practice. Great strides have been made during the recent decades
      in the methodology of hair growth trials in dermatology and cosmetology. Clinical
      evaluations benefit from a few additional specific techniques that enhance the
      perception of hair (re-) growth, shedding and alopecia. These assessments include
      the determination of hair patterning and density that may be helped by the 'black
      and-white felt' examination. Daily hair counts, the 'hair pull test' and the
      'hair feathering test' are also available. Instrumental methods provide reliable
      quantitative information that is useful if there are adequate controls. Some
      photographic methods, the trichogram, hair weighing and variants of the hair
      growth window technique including the phototrichogram, videotrichogram and
      tractio-phototrichogram provide insight into the complexities of hair cycling and
      shedding. Skin biopsy is indicated for diagnostic purposes, especially when the
      hair loss is accompanied by scarring.

PMID- 14976388
TI  - Allergenic components of Indian jujube (Zizyphus mauritiana) show IgE cross
      reactivity with latex allergen.
AB  - BACKGROUND: 'Latex-fruit syndrome' has been well documented. A prevalence of
      latex allergy among medical workers of 6.8-8.6% had been reported in Taiwan.
      However, there has been no study to determine the importance and type of fruit
      hypersensitivity in latex-allergic patients in Taiwan. This study aimed to
      identify the allergenic components of Indian jujube (Zizyphus mauritiana) and
      characterize the cross-reactivity of specific IgE antibodies to latex allergen.
      METHODS: Crude extracts were prepared from Indian jujube and from ammoniated
      natural rubber latex, and six medical workers and one patient with a history of
      fruit allergy underwent skin testing with routine allergens, latex, Indian jujube
      and other fruits. Sera from two Indian jujube skin test-positive latex-allergic
      subjects were used for allergen-specific IgE, immunoblotting, immunoblot
      inhibition and enzyme-linked immunosorbent assay (ELISA) inhibition studies.
      RESULTS: Both patients had positive skin test responses and specific IgE assays
      to Indian jujube and latex extracts. Immunoblotting revealed that IgE from both
      subjects bound to a 42-kD latex protein and a 42-kD Indian jujube protein. In
      addition, IgE from one subject bound to a 30-kD Indian jujube protein.
      Preincubation of atopic sera with Indian jujube or latex extract demonstrated
      absent and/or marked inhibition of IgE binding. Moreover, anti-Indian jujube
      protein antibody-based ELISA was able to detect latex extracts. CONCLUSIONS: Our
      results add to findings regarding the 'latex-fruit syndrome' described in the
      literature, and further study of the cross-reacting allergens identified in
      Indian jujube may help to elucidate the mechanisms underlying this syndrome.

PMID- 14976389
TI  - Purification and characterization of a major cross-reactive allergen from
      Epicoccum purpurascens.
AB  - BACKGROUND: Epicoccum purpurascens (formerly nigrum) (EP), is a ubiquitous
      saprophytic mould found both indoors and outdoors. Several studies have reported
      sensitization to EP in 5-7% of different populations worldwide. The diagnosis of
      mould allergy requires a standardized fungal extract that contains all its
      important allergenic proteins. The crude allergen extract from EP was
      standardized earlier, however none of its allergens have been purified. METHODS:
      A major allergen from spore-mycelia extract of EP was purified using concanavalin
      A (Con A) Sepharose chromatography, gel filtration and electro-elution. The
      allergen isolated was characterized for its IgE-binding ability and cross
      reactivity with five well-known allergenic fungi by ELISA and immunoblot.
      RESULTS: A 33.5-kD glycoprotein allergen of EP, Epi p 1, was purified to
      homogeneity. All the EP allergic patients' sera tested recognized this protein.
      Periodate modification of Epi p 1 showed partial loss in IgE binding while
      proteinase K treatment caused complete loss in binding to IgE. Dose-dependent
      inhibition in binding of rabbit anti Epi p 1 antibodies was obtained with Epi p
      1, Aspergillus fumigatus, Alternaria alternata, Curvularia lunata, Cladosporium
      herbarum and Fusarium solani in ELISA. Rabbit antibodies to all the above five
      fungi recognized Epi p 1 in immunoblot, confirming that Epi p 1 shares common
      epitopes with the fungi tested. CONCLUSION: A major glycoprotein allergen of 33.5
      kD was purified from EP which cross-reacts with other fungi. Hence this
      glycoprotein can be exploited to reduce the panel of allergen extracts used for
      therapy of mould allergy.

PMID- 14976390
TI  - IgE binding to raw and boiled shrimp proteins in atopic and nonatopic patients
      with adverse reactions to shrimp.
AB  - BACKGROUND: Characterization of seafood allergens is important to understand the
      immune response to these allergens. Moreover, a detailed comparison between
      atopic and nonatopic patients with adverse reactions to shrimp has never been
      reported. METHODS: Raw and boiled shrimp extracts were analyzed by immunoblotting
      using sera from 9 atopic and 7 nonatopic patients with a history of adverse
      reactions to shrimp, and 13 control subjects. Total IgE, specific IgE and skin
      prick tests (SPT) to shrimp were also investigated. RESULTS: The level of
      specific IgE to shrimp was higher in atopic patients than nonatopic patients
      (p<0.05). Symptoms, SPT results and major allergens involved were similar in
      atopic and nonatopic patients. The 16.5-kD protein had the highest frequency of
      IgE binding followed by the 40-kD protein in these patients. Other minor IgE
      binding proteins were observed at the 20-, 22-, 54-, 72-, 129- and 140-kD
      regions. Patients who had binding to the 16.5-kD protein had either positive (25%
      raw/31% cooked) or negative (13% raw/cooked) CAP-FEIA-RAST, while patients who
      recognized the 40-kD protein all had positive (31% raw/19% cooked) CAP-FEIA-RAST.
      All control subjects had negative immunoblots for these two proteins. CONCLUSION:
      The 16.5-kD protein was the most frequent protein identified regardless of CAP
      FEIA-RAST results, while the 40-kD protein was only present in patients with
      positive CAP-FEIA-RAST. Therefore, 16.5-kD protein may be an important allergen
      that is clinically relevant in both atopic and nonatopic patients with adverse
      reactions to shrimp even if it is not detected by the CAP-FEIA-RAST system.

PMID- 14976391
TI  - The FcgammaRIIa polymorphism in children with atopic diseases.
AB  - BACKGROUND: Fcgamma receptor II (FcgammaRIIa) is the most widely distributed of
      the classes of FcR and is expressed in polymorphic forms on most types of
      hematopoietic cells. Recent data suggest that this polymorphism may be relevant
      to FcgammaRIIa function. This might be linked to variability in immune response
      and therefore related to the pathogenesis of atopic diseases. The aim of the
      study was to evaluate the FcgammaRIIa polymorphism in children with atopic
      diseases. METHODS: In the study were included 140 atopic children, 77 with food
      allergy and 126 healthy subjects as the control group. The FcgammaRIIa
      polymorphism was determined using the polymerase chain reaction method. RESULTS:
      The distribution of FcgammaRIIa genotypes in atopic children did not differ from
      that of healthy controls. Moreover, there was no association between the
      FcgammaRIIa genotypes and atopic diseases. CONCLUSION: It seems that the
      FcgammaRIIa polymorphism does not represent an important genetic risk factor for
      atopic diseases susceptibility.

PMID- 14976392
TI  - Alginic acid oligosaccharide suppresses Th2 development and IgE production by
      inducing IL-12 production.
AB  - BACKGROUND: Since allergen-specific IgE is directly involved in the type I
      allergic reaction, development of a method for inhibiting Th2 responses which
      lead to the induction of IgE production would be a useful approach for preventing
      allergic disorders. The ability and mechanism of alginic acid oligosaccharide
      (ALGO), an oligosaccharide obtained from natural edible polysaccharide, for
      suppressing Th2 responses was examined in detail. METHODS: Lymph node cells
      obtained from beta-lactoglobulin (beta-LG)-primed BALB/c mice were cultured in
      vitro with an antigen for 3 days in the absence or presence of ALGO. The amount
      of cytokine in each culture supernatant was measured. The effect of ALGO on Th2
      development was also examined by using ovalbumin specific T cell receptor
      transgenic mice. Antibody production in the serum of BALB/c mice that had been
      immunized with beta-LG or beta-LG plus ALGO was investigated. RESULTS: The
      production of IFN-gamma induced by antigen stimulation was upregulated by ALGO in
      a dose-dependent manner. IL-12 production was also enhanced by ALGO, and the
      addition of the anti-IL-12 antibody to the culture abrogated the effect of ALGO.
      On the other hand, IL-4 production by antigen-stimulated splenocytes of
      transgenic mice was suppressed in the presence of ALGO. Furthermore, IgE
      production by ALGO-treated mice was significantly inhibited compared with control
      mice. CONCLUSIONS: These results indicate that ALGO suppressed antigen-induced
      Th2 development by inducing IL-12 production. ALGO also inhibited in vivo IgE
      production. These findings suggest that ALGO is expected to be an edible anti
      allergic agent.

PMID- 14976393
TI  - The prevalence of allergic sensitisation in immigrant children in The
      Netherlands.
AB  - BACKGROUND: Differences in the prevalence of allergic sensitisation have been
      reported in immigrant children living in the same urban environment. The purpose
      of this study is to investigate the prevalence of allergic sensitisation in
      school children of Dutch, Turkish and Moroccan origin. METHODS: The prevalence of
      sensitisation to aero-allergens was assessed using the skin prick test in a non
      selected sample of 512 children (response rate 54%) living in the same inner city
      district of Utrecht. In addition, exhaled nitric oxide (FeNO) was determined.
      RESULTS: The prevalence of allergic sensitisation was dependent on the ethnic
      origin. As compared with Dutch children (19.1%), a higher prevalence of allergic
      sensitisation was observed in immigrant children for whom both parents were born
      in Turkey (23.6%, not significant) or Morocco (30.6%, p<0.05). The prevalence of
      allergic sensitisation in Dutch children was nearly 2 times lower than the
      reported prevalence in German children. In all sensitised children, the mean FeNO
      value was significantly (p<0.05) higher than in non-sensitised children, and the
      mean FeNO level was highest in Moroccan children sensitised to indoor allergens.
      CONCLUSION: In The Netherlands, immigrant children show a higher prevalence of
      allergic sensitisation as compared to Dutch children.

PMID- 14976394
TI  - Aspirin sensitivity and IgE antibodies to Staphylococcus aureus enterotoxins in
      nasal polyposis: studies on the relationship.
AB  - BACKGROUND: Nasal polyposis is a multifactorial disease characterized by a
      chronic eosinophilic inflammation of the sinus mucosa, often associated with
      asthma and aspirin sensitivity. We have recently shown that the presence of IgE
      antibodies to Staphylococcus aureus enterotoxins (SAEs) was related to the
      severity of eosinophilic inflammation in nasal polyp tissue. In this study, we
      therefore aimed to determine, whether aspirin sensitivity was related to an
      immune response to SAEs, and how both criteria would be related to eosinophilic
      inflammation. METHODS: 40 subjects with nasal polyposis (NP) were classified as
      aspirin-sensitive (n=13, ASNP) or aspirin-tolerant (n=27, ATNP) based on a
      bronchial aspirin challenge test. Homogenates prepared from nasal polyp tissue
      and inferior nasal turbinates from healthy subjects (n=12) were analyzed for
      concentrations of IL-5 by enzyme immunoassay and for ECP, total and IgE to a mix
      of SAEs (A, C, TSST-1) using the ImmunoCAP system. RESULTS: Concentrations of IL
      5, ECP, total IgE, and IgE to an SAE mix were significantly increased in ASNP
      compared with ATNP patients and controls. In addition, a subgroup analysis showed
      an increase in eosinophilic markers in ATNP-SAE(+) compared to ATNP-SAE(-). This
      relationship, however, was not found in ATNP-SAE(+) and ATNP-SAE(-) subjects,
      indicating that SAE immune response is overlapped or not relevant in this
      condition. CONCLUSIONS: Aspirin sensitivity was associated with increased
      concentrations of eosinophil-related mediators, as well as IgE antibodies to SAEs
      in nasal polyp tissue. However, a direct impact of S. aureus could not be
      established. It seems that aspirin sensitivity and immune reactions to SAEs are
      independently related to eosinophilic inflammation.

PMID- 14976395
TI  - Prevalence of serum IgE antibodies to the Staphylococcus aureus enterotoxins
      (SAE, SEB, SEC, SED, TSST-1) in patients with persistent allergic rhinitis.
AB  - BACKGROUND: Enterotoxins produced by Staphylococcus aureus and their specific IgE
      antibodies were thought to be important in worsening atopic dermatitis. However,
      few studies have documented an association between S. aureus or its exotoxins and
      exacerbations of upper airway/nasal disease. In the current study, we determined
      the prevalence of serum-specific IgE towards staphylococcal enterotoxin A, B, C,
      D (SEA, SEB, SEC, SED) and toxic shock syndrome toxin 1 (TSST-1) in patients
      suffering from rhinitis and/or asthma due to allergy. Therefore, we examined
      whether SEA, SEB, SEC, SED and TSST-1 were important in worsening the clinical
      status of patients allergic to house dust mites by means of assessing serum
      eosinophil cationic protein (ECP), which is thought to be a reliable marker of
      asthma and rhinitis severity. METHODS: 198 patients with persistent allergic
      rhinitis and/or asthma due to house dust mites were evaluated. Specific IgE
      towards SEA, SEB, SEC, SED, TSST-1, timothy grass and birch pollen recombinant
      allergens, and other aeroallergen extracts from common allergen sources were
      evaluated by the Pharmacia CAP System. Serum ECP was assessed, too. RESULTS: The
      percentages of sensitization to staphylococcal enterotoxins of 198 house dust
      mite-allergic patients were as follows: TSST-1-specific IgE 24.7% (n=49), SEC
      specific IgE 22.2% (n=44), SEB-specific IgE 15.1% (n=30), SEA-specific IgE 9.1%
      (n=18), and SED-specific IgE 5.5% (n=11). Out of 198 individuals allergic to
      house dust mites 136 patients suffering from persistent rhinitis were subdivided
      into two subgroups: 53 patients with serum-specific IgE to at least one
      staphylococcal enterotoxin and 83 patients without specific IgE towards
      staphylococcal enterotoxins. Patients sensitive to staphylococcal enterotoxins
      had higher serum ECP levels than patients lacking specific IgE to SEA, SEB, SEC,
      SED and TSST-1(geometric mean 24.3 vs. 16.6 microg/100 ml; p=0.029), as well as
      total IgE levels (geometric mean 564 vs. 161 kU/l, p=0.00063) and specific IgE to
      Dermatophagoides pteronyssinus (geometric mean 16.7 vs. 6.6 kU/l; p=0.0235) and
      Dermatophagoides farinae (geometric mean 18.6 vs. 7.8 kU/l; p=0.0246).
      CONCLUSION: A status of sensitization to staphylococcal enterotoxins seems to be
      a factor increasing serum ECP, which is thought to be a reliable marker of
      clinical severity of allergic disease. Therefore, the evaluation of SEA, SEB,
      SEC, SED and TSST-1-specific IgE antibodies may have additional significance for
      the prognosis of persistent allergic diseases of the upper airway.

PMID- 14976396
TI  - Suppressive activity of fexofenadine hydrochloride on thymus- and activation
      regulated chemokine production from human peripheral blood leukocytes in response
      to antigenic stimulation in vitro.
AB  - BACKGROUND: Thymus- and activation-regulated chemokine (TARC) is accepted as
      being an important molecule in the development and maintenance of allergic
      diseases. However, there is little information about the influence of
      antiallergic agents on TARC production after allergen challenge. The aim of this
      study is to examine the influence of fexofenadine hydrochloride (FEX), an H1
      receptor antagonist, on TARC production from human peripheral blood leukocytes
      (PBL) using an in vitro cell culture technique. METHODS: PBL prepared from donors
      with pollinosis were cultured with either Japanese cedar pollen allergen, Cry j
      1, or interleukin (IL)-4 in the presence of various doses of FEX for 6 days.
      Levels of TARC and the T cell cytokines IL-4 and interferon (IFN)-gamma in
      culture supernatants were examined by ELISA. RESULTS: FEX did not affect PBL
      proliferation induced by Cry j 1 stimulation, even when 500 ng/ml of the agent,
      twice the therapeutic blood levels, was added to cell cultures as assessed by
      measuring 3H-thymidine incorporation into DNA. On the other hand, FEX at 250
      ng/ml (but not 125 ng/ml), similar to therapeutic blood levels, significantly
      inhibited the ability of PBL to produce IL-4 (but not IFN-gamma), which was
      enhanced by Cry j 1 stimulation. FEX at concentrations of more than 250 ng/ml
      also exerted a suppressive effect on TARC production from PBL in response to Cry
      j 1 and IL-4 stimulation in vitro. CONCLUSION: This inhibitory action of FEX may
      be partially responsible for the attenuating effect of the agent on allergic
      diseases.

PMID- 14976397
TI  - Reduced CD40L expression on ex vivo activated CD4+ T-lymphocytes from patients
      with excellent renal allograft function measured with a rapid whole blood flow
      cytometry procedure.
AB  - BACKGROUND: The CD40-CD40L (CD154) costimulatory pathway plays a critical role in
      the pathogenesis of kidney allograft rejection. In renal transplant biopsies,
      CD4+CD40L+ graft-infiltrating cells were detected during chronic rejection in
      contrast to acute rejection episodes. Using a rapid noninvasive FACS procedure,
      we were able to demonstrate CD40L upregulation in peripheral blood of patients
      with chronic renal allograft dysfunction. MATERIALS AND METHODS: Whole blood from
      recipients of renal allografts was stimulated with PMA and ionomycin and measured
      by flow cytometry. Patients were assigned to three groups based on transplant
      function. Group 1: 26 patients with excellent renal transplant function; group 2:
      28 patients with impaired transplant function; group 3: 14 patients with chronic
      allograft dysfunction and group 4: 8 healthy controls. RESULTS: The median
      percentage +/- SEM of CD4+/CD40L+ cells stimulated ex vivo at 10 ng/ml PMA was as
      follows: group 1: 28.3 +/- 4.1%; group 2: 18.4 +/- 2.4%; group 3: 50.1 +/- 5.0%
      and group 4: 40.4 +/- 3.4%. Subdivisions of groups 2 and 3 resulted in different
      CD40L expression patterns. Patients with increased serum creatinine since the
      initial phase after transplantation (groups 2a and 3a) revealed a higher
      percentage of CD4+CD40L+ cells than patients showing a gradual increase over time
      (groups 2b and 3b). Consequently, patients of group 3a exhibited a significantly
      reduced transplant function compared with those of group 3b. CONCLUSION: After
      PMA + ionomycin stimulation, patients with excellent kidney graft function
      displayed significantly reduced expression of CD40L surface molecules on CD4+
      cells early after transplantation. Those with a chronic dysfunction of the renal
      graft showed significantly more CD4+ cells expressing CD40L compared to the other
      transplanted groups. These results demonstrate that the percentage of CD4+CD40L+
      cells stimulated ex vivo in peripheral blood may be a valuable marker for chronic
      allograft nephropathy.

PMID- 14976398
TI  - Expression of functional activating and inhibitory Fcgamma receptors on human B
      cells.
AB  - BACKGROUND: The CD32 (FcgammaII) receptor is involved in the regulation of the B
      cell response to antigen. The sole Fc receptor demonstrated in mice is the
      inhibitory FcgammaIIB receptor. Crosslinking this receptor does not lead to
      downstream signaling or cell activation. Instead, when immune complexes bind to
      Fcy on murine B cells, cell activation through the B cell antigen receptor is
      attenuated. The objective of this study was to evaluate the expression of the
      FcgammaII receptor and the response to immune complex stimulation in human B
      cells. METHODS: Human lymphoblastoid, peripheral and tonsillar B cells were
      stained with anti-CD32 antibodies IV.3 and 8.26 to determine the relative
      expression of the activating (FcgammaIIA) and inhibitory (FcgammaIIB) isoforms of
      CD32. Tetanus immune complexes were added to B cells and the activation of c-Jun
      amino-terminal kinase was assayed. RESULTS: Unlike murine cells, human B cells
      express high levels of the activating form of the Fcgamma receptor IIA. Addition
      of immune complexes to peripheral B cells resulted in signaling of Jun kinase, an
      important downstream kinase involved in the regulation of B cell function. The
      level of expression of FcgammaIIA on human B cells was not uniform, but depended
      on activation status. Peripheral blood B cells expressed high levels of
      FcgammaIIA, while tonsillar B cells predominantly expressed FcgammaIIB.
      Furthermore, when peripheral B cells were activated, the expression of FcgammaIIA
      relative to FcgammaIIB decreased. CONCLUSION: The response of human B cells to
      binding of immune complexes depends on the relative expression of activating
      (FcgammaIIA) versus inhibitory (FcgammaIIB) receptors.

PMID- 14976399
TI  - The influence of prelabor rupture of the membranes on the levels of oral mucosal
      immunoglobulins in the neonate.
AB  - Oral mucosal immunoglobulins play an important role in the human immune system as
      a first-line defense against viral and bacterial infection. Secretory
      immunoglobulin A (sIgA), IgD and the free secretory component (FSC) can be
      determined in the first days of life; however, it is yet unknown which events
      influence the local synthesis of the immunoglobulins. The aim of this study was
      to evaluate the influence of prelabor rupture of the membranes (PROM) within a
      period of 24 h on the synthesis of oral mucosal sIgA, IgD, FSC and albumin of
      neonates in their first day of life. Comparison of 35 neonates with a history of
      PROM with a control group of 44 term neonates revealed no significant differences
      neither with respect to sIgA, IgD, FSC nor to albumin. The results indicate that
      PROM within a period of 24 h does not significantly increase the synthesis of
      oral mucosal immunoglobulins in neonates in the first day of life.

PMID- 14976400
TI  - Monochorionic triplets following intracytoplasmic sperm injection: a report of
      two consecutive cases.
AB  - Monochorionic triplet pregnancies are very rare. Here we report 2 cases of
      multiple pregnancies with monochorionic triplets following intracytoplasmic sperm
      injection (ICSI) and day 3 embryo transfer. The 2 women concomitantly underwent
      controlled ovarian hyperstimulation due to male factor infertility. Following
      oocyte retrieval, ICSI and assisted hatching (AH) were performed, and the 2 women
      conceived consecutively. One patient had a quadruplet pregnancy, which included
      monochorionic triplets, while the other had monochorionic triplets. Selective
      embryo reduction by intracardiac KCl injection targeted at 2 of the triplets was
      performed on the patient with the quadruplet pregnancy, but the third triplet
      also died. The gestation continued as a singleton pregnancy, and the patient gave
      birth to a healthy female baby at 38 weeks. The other patient gave birth to 3
      healthy female babies at 34 weeks. Possible etiologic factors for the formation
      of monozygotic splitting among women undergoing assisted reproduction treatment
      are discussed.

PMID- 14976401
TI  - Imaging CFTR: a tail to tail dimer with a central pore.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a protein that
      belongs to the superfamily of ATP binding cassette (ABC) transporters. Mutations
      in the CFTR gene cause cystic fibrosis, an autosomal recessive disorder. The
      function of CFTR is versatile. It can serve as a regulatory protein, as a
      membrane transporter and as an ion channel. Dimerization of CFTR is necessary for
      full ion channel function although structural details of CFTR in native membrane
      are yet unknown. In order to identify CFTR in native plasma membrane we applied
      atomic force microscopy (AFM) to inside-out oriented membrane patches of CFTR
      expressingXENOPUS LAEVIS oocytes after cAMP stimulation. First, oocytes were
      injected with CFTR-cRNA and, three days later, voltage-clamped verifying
      successful CFTR expression and incorporation into the plasma membrane. Then,
      plasma membrane patches were isolated, placed inside-out on appropriate substrate
      and incubated with gold-labelled antibodies against the C-terminus of CFTR.
      Finally, the intracellular surface of the plasma membrane was scanned by AFM. In
      close vicinity to the immunogold labels we detected ring-like structures with
      bipartite symmetry. The substructure of the ring, formed by the extramembrane
      protein domains of CFTR, is consistent with the model of a CFTR dimer. Derived
      from AFM molecular mass analysis of the intramolecular domains we conclude that
      two CFTR molecules line up in parallel, tail by tail, forming a pore in its
      center. This molecular arrangement could represent the CFTR chloride channel
      configuration, operative in native plasma membrane.

PMID- 14976402
TI  - Arrhythmia in isolated prenatal hearts after ablation of the Cav2.3 (alpha1E)
      subunit of voltage-gated Ca2+ channels.
AB  - A voltage-gated calcium channel containing Cav2.3e (alpha1Ee) as the ion
      conducting pore has recently been detected in rat heart. Functional evidence for
      this Ca2+ channel to be involved in the regulation of heart beating, besides L-
      and T-type channels, was derived from murine embryos where the gene for Cav1.2
      had been ablated. The remaining "L-type like" current component was not related
      to recombinant splice variants of Cav1.3 containing channels. As recombinant
      Cav2.3 channels from rat were reported to be weakly dihydropyridine sensitive,
      the spontaneous activity of the prenatal hearts from Cav2.3(-|-) mice was
      compared to that of Cav2.3(+|+) control animals to investigate if Cav2.3 could
      represent such a L-type like Ca(2+) channel. The spontaneous activity of murine
      embryonic hearts was recorded by using a multielectrode array. Between day 9.5
      p.c. to 12.5 p.c., the beating frequency of isolated embryonic hearts from Cav2.3
      deficient mice did not differ significantly from control mice but the coefficient
      of variation within individual episodes was more than four-fold increased in
      Cav2.3-deficient mice indicating arrhythmia. In isolated hearts from wild type
      mice, arrhythmia was induced by superfusion with a solution containing 200 nM SNX
      482, a blocker of some R-type voltage gated Ca2+ channels, suggesting that R-type
      channels containing the splice variant Cav2.3e as ion conducting pore stabilize a
      more regular heart beat in prenatal mice.

PMID- 14976403
TI  - A novel non-neuronal hSK3 isoform with a dominant-negative effect on hSK3
      currents.
AB  - We have identified a hSK3-transcript, hSK3_ex1c, which is generated by
      alternative splicing. Isoform hSK3_ex1c lacks the cytosolic N-terminus and the
      first transmembrane helix and is exclusively expressed in non-neuronal tissues.
      hSK3 transfected tsA cells showed a Ca2+-activated K+ current in patch-clamp
      experiments, whereas hSK3_ex1c transfected cells and cells co-transfected with
      both isoforms did not. We fused both isoforms to fluorescence proteins and
      observed hSK3 localization predominantly in the plasma membrane. The co
      expression of hSK3 + hSK3_ex1c resulted in their cytoplasmic co-localization.
      Thus, hSK3_ex1c has a dominant-negative effect on hSK3 by preventing its
      transport into the plasma membrane.

PMID- 14976404
TI  - Differential alterations of receptor densities of three muscarinic acetylcholine
      receptor subtypes and current densities of the corresponding K+ channels in
      canine atria with atrial fibrillation induced by experimental congestive heart
      failure.
AB  - Parasympathetic tone and congestive heart failure (CHF) are two of promoting
      factors in initiation and perpetuation of atrial fibrillation (AF). Recent
      studies indicate co-existence of multiple muscarinic acetylcholine receptor
      subtypes (mAChRs) that mediate several distinct K+ currents in the heart; inward
      rectifier K+ current IKACh by the M2, and two delayed rectifier K+ currents IKM3
      and IK4AP by the M3 and M4 receptors, respectively. We studied the alterations of
      atrial mAChRs and their coupled K+ channels in the setting of AF in dogs with
      ventricular tachypacing-induced CHF. Whole-patch-clamp recordings showed that the
      current densities of IKACh (induced by 1 mM acetylcholine) and IK4AP (induced by
      1 mM 4-aminopyridine) were n45% and n55% lower, respectively, while that of IKM3
      (induced by 10 mM choline) was n75% higher, at a plateau voltage of 0 mV in
      atrial myocytes from CHF than those from healthy hearts. In healthy hearts, IKACh
      comprised >60%, and IKM3 and IK4AP <30%, of the total outward K+ currents
      mediated by mAChRs at depolarized potentials (between -20 mV and +50 mV). In AF
      atria of CHF dogs, however, the contribution of IKM3 increased to approximately
      50%, exceeding those of IKACh or IK4AP. Western blot analyses with atrial
      membrane protein samples indicated that receptor densities of the M2 and M4
      subtypes decreased by approximately 33% and approximately 22%, respectively,
      whereas that of the M3 subtype increased by approximately 2.3 folds, in parallel
      to the alterations of the corresponding K+ currents. We conclude that
      differential alterations of mAChR subtypes underlie differential alterations of
      their coupled K+ channels in AF atria and these differential alterations may
      contribute to atrial remodeling in AF induced in the setting of CHF.

PMID- 14976405
TI  - Heat shock protein 90 recognized as an iron-binding protein associated with the
      plasma membrane of HeLa cells.
AB  - Heat shock protein 90 (Hsp90) is a molecular chaperone abundant in eukaryotic
      cells. However, its exact role is not completely understood yet. Employing an
      iron-binding assay and mass spectrometric analysis, we have identified human
      Hsp90 as an iron-binding protein in membrane protein preparations of human HeLa
      cells. Western blot analysis and confocal microscopy confirmed that a portion of
      cellular Hsp90 is associated with the plasma membrane, but it does not seem to be
      expressed on the cell surface. The iron-binding assay with purified human Hsp90
      confirmed iron binding by Hsp90. Thus we suggest that Hsp90 is an iron-binding
      protein associated with the plasma membrane.

PMID- 14976406
TI  - Inhibition of mitochondria and extracellular acidification enhance achratoxin A
      induced apoptosis in renal collecting duct-derived MDCK-C7 cells.
AB  - Ochratoxin A (OTA) is a potent nephrotoxin and suspected to be involved in the
      etiology of Balkan endemic nephropathy. Nanomolar concentrations of this
      mycotoxin induce apoptosis in renal collecting duct-derived cells (MDCK-C7 cells,
      resembling principal cells). We studied the role of mitochondria in this process
      by inhibition of the mitochondrial respiratory chain, the F1FO-ATP synthase or by
      uncoupling. Also, the role of intra- and extracellular pH in apoptosis induction
      was investigated. Activation of caspase-3 and DNA ladder formation were used to
      monitor the apoptotic response. When cells were incubated with inhibitors of the
      mitochondrial respiratory chain or an inhibitor of the ATP-synthase, OTA-induced
      apoptosis was enhanced dramatically. Also, mitochondrial uncoupling potentiated
      the effects of OTA. OTA-induced apoptosis was not dependent on a decrease of the
      mitochondrial potential. Mitochondrial blockade led to medium acidification due
      to enhanced production of lactic acid. Artificial extracellular acidification
      potentiated OTA-induced caspase-3 activation. Artificial extracellular
      alkalization had no influence on caspase-3 activity. Intracellular pH after 24
      hours exposure to inhibitors of mitochondria or acidic or alkaline media did not
      correlate with caspase-3 activity but correlated with caspase-3 activity when OTA
      was present: acidic intracellular pH (pHin) was associated with higher caspase-3
      activity as compared to alkaline pHin. We conclude that extra- and intracellular
      pH are important factors in OTA-induced apoptosis in MDCK-C7 cells. The
      physiologically changing pH conditions in the collecting duct can thus alter or
      even aggravate the toxic effects of OTA.

PMID- 14976407
TI  - Conjugated linoleic acid--mediated apoptosis in Jurkat T cells involves the
      production of reactive oxygen species.
AB  - The pro-apoptotic ability of conjugated linoleic acid (CLA) has been partly
      accounted for its anticarcinogenic effect although the precise mechanism of
      action remains elusive. In this study we characterized the biochemical events
      governing CLA-mediated apoptosis in Jurkat T cells. CLA induced a time-and dose
      dependent activation of caspase-3. Pre-treatment with antioxidant molecules
      (trolox and quercetin), antioxidant enzymes (catalase and superoxide dismutase)
      metal chelator (EDTA), reducing agent (N-acetyl-L-cysteine), NADPH oxidase or
      protein kinase C (PKC) inhibitor (diphenyleneiodinium and G 6976, respectively)
      suppressed CLA-mediated caspase-3 activation. Moreover, CLA treatment increased
      the NADPH oxidase activity and depleted the intracellular pool of reduced
      glutathione. These results suggested that CLA can trigger apoptosis through an
      oxidative stress mediated by the PKC/NADPH oxidase pathway. The proposed
      mechanism provides a new insight into the anticancer activity of CLA.

PMID- 14976408
TI  - Early and late apoptosis events in human transformed and non-transformed
      colonocytes are independent on intracellular acidification.
AB  - Intracellular acidification is discussed to play a pivotal role in the process of
      programmed cell death by providing an intracellular environment optimal for the
      activation of caspases and the execution of apoptosis. Using three human colon
      epithelial cell lines we tested whether effects on early and late apoptosis
      markers can be related to changes in intracellular pH (pHi). Caspase-3-like
      activity and plasma membrane disintegration served as measures of early apoptosis
      whereas nuclear fragmentation served as indicator of late apoptosis events. The
      pHi was measured using the pH-sensitive dye 2 , 7 -BIS (2-carboxyethyl-5-(6)
      carboxyfluorescein. Six flavonoids differing in apoptosis inducing activity were
      employed as tools. In HT-29 cells, quercetin and flavone proved to potently
      increase apoptosis without altering pHi. In Caco-2 cells, quercetin and flavone
      increased early and late apoptosis parameters associated with a concomitant
      decline in pHi. However, addition of imidazole prevented the acidification
      without altering the apoptotic response to the flavonoids. In NCOL-1 cells, only
      quercetin was able to induce apoptosis and changes observed correlate with the
      observed initial intracellular acidification rate. Here too, imidazole prevented
      the pHi decline but failed to affect apoptosis execution. In conclusion,
      apoptosis in human colonocytes is not affected by alterations in pHi.

PMID- 14976409
TI  - PKA regulation of bicarbonate and lactate movements across rat jejunal plasma
      membranes.
AB  - BACKGROUND/AIMS: Evidence was previously given that the mechanisms involved in
      bicarbonate and lactate movements across rat jejunal enterocyte are modulated by
      PKC and Ca2+/CaM. Aim of this study was to investigate the possible role of PKA
      on bicarbonate and lactate transports. METHODS: Enzymatic assays in isolated
      plasma membranes were performed. Moreover membrane vesicles, transiently opened
      and resealed, were treated with a phosphorylating solution (leading to PKA
      activation) and were used after that to perform uptake studies. RESULTS:
      Enzymatic assays give evidence for the presence of PKA in plasma membranes from
      rat jejunum. Uptake experiments suggest that PKA stimulates the two systems that
      accomplish basolateral HCO3- efflux from the enterocyte, namely Cl-/ HCO3-
      exchanger and HCO3- conductance, without affecting HCO3- influx from the lumen
      mediated by Na+/H+ exchanger activity. Moreover basolateral H+-lactate symporter
      is stimulated by PKA, as well as the brush border isoform of Na+-glucose
      cotransporter SGLT1. CONCLUSION: PKA activation evokes individual responses that
      could be coordinated through cellular metabolism.

PMID- 14976410
TI  - Distinct signalling cascades downstream to Gsalpha coupled dopamine D1-like NHE3
      inhibition in rat and opossum renal epithelial cells.
AB  - Dopamine D1-like receptors are linked via G proteins to multiple cellular
      signaling pathways, namely adenylyl cyclase (AC) and phospholipase C (PLC). We
      have previously shown that the D1-mediated inhibition of Na+-K+-ATPase activity
      in OK cells involves the sequential activation of the AC-protein kinase A (AC
      PKA) and the PLC-protein kinase C (PLC-PKC) pathways. The present study evaluated
      signaling cascades involved in dopamine-mediated inhibition of Na+/H+ exchanger
      isoform 3 (NHE3) in rat and opossum renal cells. Na+/H+ exchanger activity was
      assayed as the initial rate of intracellular pH (pHi) recovery after an acid
      load. Vmax values (in pH units/s) for Na+-dependent pHi recovery in rat cells
      (0.0097+/-0.0007) were greater (P<0.05) those in opossum cells (0.0063+/-0.0007),
      with similar Km values (in mM) for Na+ (rat, 35+/-9; opossum, 24+/-9). The IC50
      values for EIPA and amiloride induced decrease in NHE activity in rat and opossum
      kidney cells are in agreement with the observation that rat renal proximal
      tubules and opossum kidney cells express mainly the NHE3 isoform. The D1-like
      receptor agonist SKF 38393 inhibited NHE3 activity in a concentration-dependent
      manner in both rat and opossum cells. The D1-mediated inhibition of NHE3 was
      prevented either by the D1-like receptor antagonist SKF 83566 (1 microM),
      overnight treatment with cholera toxin (500 ng/ml) and the PKA antagonist H-89
      (10 microM) in rat and opossum kidney cells. The effect of SKF 38393 was
      abolished by the PKC antagonist chelerythrine (1 microM), or the PLC inhibitor U
      73,122 (3 microM) in opossum cells, but not in rat cells. In addition, dibutyril
      cAMP (dB-cAMP; 500 microM) was found to increase PLC activity in OK cells but not
      in rat cells. The effect of D1-like dopamine agonist was accompanied by increases
      in cyclic AMP production in rat and opossum cells. The inhibitory effect of SKF
      38393 (1 microM) on NHE3 activity was abolished in rat and opossum cells pre
      treated with the anti-GSalpha antibody, but not in cells treated with the anti
      Gq/11 alpha antibody. It is concluded that D1 agonists decrease NHE3 activity by
      classical stimulation of AC and PKA via GSalpha proteins in rat kidney cells. By
      contrast, the D1-mediated inhibition of NHE3 in renal opossum cells involves a
      peculiar mechanism with AC-PKA and PLC-PKC pathways.

PMID- 14976411
TI  - Neutrophil transmigration in renal proximal tubular LLC-PK1 cells.
AB  - BACKGROUND/AIMS: Adhesion of intratubular leukocytes to proximal tubules in
      biopsies of patients with rapidly progressive glomerulonephritis and the
      appearance of leukocytes in the urine in interstitial nephritis suggest
      interactions between leukocytes and tubular epithelia in renal disease. The
      present study was performed to investigate whether incubation of tubular
      epithelia with cytokines or endotoxin (LPS) does stimulate adhesion and migration
      of leukocytes through these epithelia in vitro. METHODS: Experiments determined
      adhesion of PMN to LLC-PK cells cultured on tissue culture plates and
      transepithelial migration (TEM) through LLC-PK monolayers cultured on microporous
      membranes. Measurements of transepithelial electrical resistance (TER), cytokine
      release into apical or basolateral compartments and chemotactic activities of
      apical and basolateral supernatants were performed. RESULTS: Preincubation of LLC
      PK cells with either TNFalpha or LPS resulted in stimulation of PMN adhesion and
      consequently PMN migration through LLC-PK monolayers in both apical-to
      basolateral and basolateral-to-apical direction. TEM was not associated with a
      reduction of TER. Although largely apical IL-8 secretion by LLC-PK cells was
      found, apical-to-basolateral migration occurred against a concentration gradient
      of IL-8 and could not be inhibited by IL-8 antibodies. Chemotactic activities of
      supernatants were slightly increased by TEM but did not show any significant
      differences between apical and basolateral compartments independent of the
      direction of PMN migration. TEM in basolateral-to-apical direction was about
      twice as efficient as in apical-to-basolateral direction (Transmigration Index =
      3,92 +/- 0,55 and 2,28 +/-,21, respectively). Only basolateral-to-apical TEM
      could be partly inhibited by preincubation of basolateral membrane with IL-8
      antibodies. CONCLUSION: Inflammatory mediators stimulate PMN adherence to LLC-PK
      cells and subsequently TEM. The mechanisms involved in TEM stimulated by
      cytokines or endotoxin appear to be rather changes in surface receptor properties
      of LLC-PK cells than chemotactic stimuli. Basolateral-to-apical TEM appears to be
      the favored direction most likely augmented by IL-8 associated haptotactic PMN
      stimulation.

PMID- 14976412
TI  - Kidney and colon electrolyte transport in CHIF knockout mice.
AB  - Corticosteroid hormone induced factor (CHIF) is a small epithelial-specific
      protein regulated by aldosterone and K+ intake. It is a member of the FXYD family
      of single span transmembrane proteins involved in the regulation of ion
      transport. Recent data have suggested that CHIF interacts with the a subunit of
      the Na+-K+-ATPase and increases the pump's affinity to cell Na+. CHIF knockout
      (KO) mice have mild renal phenotype under low Na+ or high K+ diets. The present
      study further characterizes kidney electrolyte metabolism in CHIF KO mice and
      describes abnormalities in the colonic ion transport function. Kidney: KO mice
      were not compromised in salt and water balance under resting conditions.
      Fractional excretions (FE) of Na+ and K+ were normal and the animals had no
      deficit in the adaptation to low Na+ or high K+ intake. Glucocorticoid treatment
      did not unmask any difference. The effects of amiloride on Na+ absorption were
      not different at any treatment protocol. In contrast, FEK+ was reduced by 35% in
      KO mice under low Na+ intake. COLON: Amiloride inhibitable Na+ absorption was
      reduced in distal colon by 42%, 54% and 58% under control conditions,
      glucocorticoid treatment and low Na+ intake, respectively. Also, the cAMP
      dependent ion transport was significantly diminished. Forskolin induced
      equivalent short circuit current (I'SC) was reduced by 41%, 32% and 58%, under
      control conditions, high K+, and low Na+ intake, respectively. The present
      findings support a role of CHIF as an indirect modulator of several different ion
      transport mechanisms and are consistent with regulation of the Na+-K+-ATPase as
      the common denominator.

PMID- 14976413
TI  - Prenatal ethanol administration: effects on IgG absorption during postnatal
      development in the rat intestine.
AB  - The effect of feeding 1 ml of 30% ethanol to pregnant female rats during
      gestation on the IgG absorption has been studied in the developing intestine.
      Pups born to dams fed ethanol during gestation exhibited a significant decline in
      body weight (p < 0.01), intestinal weight (p < 0.01), and intestinal length (p <
      0.05) as compared with the controls. Intestinal weight to body weight or
      intestinal weight to intestinal length ratios were essentially similar under
      these conditions. The intestinal absorption of IgG was considerably reduced in 12
      day-old pups (p < 0.01) exposed to ethanol in utero as compared with the control
      group. A similar decrease in the binding of [(125)I]IgG to microvillus membranes
      was observed on days 12 and 20 under these conditions. Northern blot analysis
      revealed low levels of mRNA encoding IgG Fc receptor in ethanol-exposed pups as
      compared with the controls. These findings suggest that prenatal ethanol
      ingestion impairs the absorption of IgG as a consequence of the downregulation of
      IgG Fc receptor expression in the rat intestine.

PMID- 14976414
TI  - The application of alkaline phosphatase labeled HBV probe in serum detection.
AB  - A method using non-radioactive material alkaline phosphatase to label HBV DNA as
      probe has been studied and used in clinical experiments to detect the HBV DNA in
      hepatitis serum. Alkaline phosphatase coupled with polyethyleneimine (PEI) using
      P-benzoquine as cross-linking reagent. The modified phosphatase was covalently
      linked to single strand DNA using glutraldehyde. Such single strand DNA enzyme
      complexes have been tested for blot hybridization, after hybridization and
      incubation with a substrate solution, sequences complementary to the probe can be
      visualized directly in 1 h. The minimum amount about 10 pg of target DNA has been
      detected in this way, 32P labeled probes are autoradiography 1 h after
      hybridization can only detect 10 ng, so the enzyme labeled probe is more
      sensitive than isotope labeled probe in 1 h fast test. Comparing the enzyme
      labeled HBV DNA probe with 32P labeled the same one, positive proportion of
      detecting the HBV DNA in hepatitis patients was about 95.7%. Because the positive
      patient's serum detected by 32P labeled probe were selected through 1- week
      radiation, Alkaline Phosphatase labeled probes are color developed for only 1 h.
      Our experiment certified that it is a sensitive, specific, easy, rapid, safe and
      economical probe labeling and clinical virus DNA detection method.

PMID- 14976415
TI  - High reactivation of BK virus variants in Asian Indians with renal disorders and
      during pregnancy.
AB  - There is resurgence of interest in the study of occurrence, genotype and
      pathogenic associations of human Polyomavirus BK and JC in recent years. In the
      present study, we have ascertained the presence of BK virus shed in the urine
      samples of pregnant women and immunocompromised patients, for the first time in
      Asian Indian population, and have also characterised the prevalent genotypes of
      the non-coding control regions (NCCRs) of these natural isolates. The results
      strongly suggest a very high incidence, as well as degree, of BK virus
      reactivation in this population groups assayed. Approximately 65% of the patients
      and pregnant women together, tested positive based on polymerase chain reaction
      (PCR) analysis, and these results were further confirmed by Southern
      hybridisation and dot blot against BKV specific probes. The NCCRs of the several
      Indian endemic strains were analysed by sequencing PCR products, amplified
      directly from urine samples, with oligonucleotide primers designed from the
      constant region of T-Antigen and VP2 coding sequences. The typical features of
      the NCCRs of these Indian strains appeared to be comparable and related to the
      archetypal strain BKV (WW) with some alterations in few key positions. Apart from
      these subtle alterations, neither any major DNA rearrangement within the NCCR
      region nor any drastic modification marked BKV strains found in nephropathy and
      in the healthy subjects (pregnancy). However, in some of the immunocompromised
      patients studied, the degree of reactivations reflected by viruria, appeared to
      be much higher compared to other reports.

PMID- 14976416
TI  - Rinderpest virus RNA polymerase subunits: mapping of mutual interacting domains
      on the large protein L and phosphoprotein p.
AB  - The RNA dependant RNA polymerase of negative sense RNA viruses is composed of two
      subunits - the Large protein (L) and the Phosphoprotein (P). These two proteins
      have to form a complex in order to carry out genome transcription and
      replication. Employing the baculovirus expression system, we demonstrate here,
      the specific in vivo interaction between the L and P proteins of Rinderpest virus
      and also the stabilization of L protein when it is present as L + P complex. The
      regions on either protein involved in such interaction has been studied using the
      yeast two-hybrid system which indicates that the P binding region resides within
      the amino terminal 380 amino acid residues of L protein. The L binding region on
      P protein has been mapped to lie within 347-490 amino acids.

PMID- 14976417
TI  - Molecular characterization of duck hepatitis B virus isolates from South African
      ducks.
AB  - The objective of the study was to characterize the genome of duck hepatitis B
      virus (DHBV) isolates from South African Pekin ducks. Duck serum and liver
      samples were collected from two commercial duck farms from geographically
      distinct regions of South Africa. In total, 498 duck serum samples were tested
      for the presence of DHBV DNA using either sub-genomic or full-length polymerase
      chain reaction (PCR) assays. The overall prevalence of DHBV infection in South
      African ducks was 47%. In addition, 30% of 59 liver tissues tested were DHBV DNA
      positive. Six randomly selected serum or liver samples were used to clone and
      sequence the genomes of the South African DHBV strains. All six isolates had DHBV
      genomes of 3,021 nucleotides with three characteristic overlapping reading frames
      encoding the polymerase, surface and core gene products. No X-like gene with a
      traditional start codon was found. Following phylogenetic analysis, the South
      African DHBV isolates clustered with DHBV isolates from other "Western"
      countries, including United States of America, Canada, Germany and India. On
      translation of the open reading frames, the South African isolates were found to
      share signature amino acids in the polymerase and surface genes with the
      "Western" country isolates as opposed to those of Chinese DHBV isolates.

PMID- 14976418
TI  - Genetic characterization of the M RNA segment of Crimean-Congo hemorrhagic fever
      virus strains isolated in Russia and Tajikistan.
AB  - The data on the structure of the M genome segment of CCHF virus strains from
      Russia and Central Asia (Tajikistan) are presented. Data obtained have been
      compared with other available published sequences of the middle segment of
      strains from China, Nigeria, and Pakistan. It has been found that all the known
      strains can be divided into four genetic groups, based on the nucleotide sequence
      of the M genome segment and an amino acid sequence of the glycoprotein precursor
      it encodes, whereas VLG/TI29414 and STV/HU29223 strains from Russia form a
      separate group. The CCHF virus strain from Tajikistan, TADJ/HU8966, was
      genetically related to strains 7803 and 75024 from China, and together with these
      and the Nigerian IbAr 10200 strain, it forms another group.

PMID- 14976419
TI  - Phylogenetic analysis and homologies of the replicase of tomato leaf curl
      geminiviruses: implications for obtaining pathogen derived resistance.
AB  - Geminiviruses encode a replication initiator protein, Rep, which binds to
      iterated DNA motifs functioning as essential elements for virus specific
      replication. Rep protein gene of three isolates of whitefly transmitted
      geminivirus causing leaf curl disease of tomato in India were amplified, cloned
      and sequenced. Nucleotide sequence and the derived amino acid sequence for the
      replicase gene of these isolates was determined and included in an analysis with
      the published sequences. Phylogenetic relationship clearly indicates two subsets,
      one belonging to Tomato leaf curl virus (ToLCV) having bipartite genome and the
      other having the monopartite genome. Comparisons of various functional domains
      and motifs involved in specificity determinants, DNA-binding and catalysis were
      discussed. The implications of the sequence analysis were discussed with respect
      to the strategy for the generation of engineered resistance having wide spectrum
      applications.

PMID- 14976420
TI  - Complete nucleotide sequence of a mumps virus genotype I strain isolated in
      Korea.
AB  - The complete nucleotide sequence of mumps virus isolated in Korea,
      Dg1062/Korea/98 (Dg1062), was determined. As other mumps viruses, its genome was
      to be 15,384 nucleotides (nts) in length and encoded seven proteins. The both 5'
      and 3' ends were confirmed to be 55 and 24 nts by RACE method, respectively. The
      full-length nucleotide sequence of Dg1062 isolate differed from other strains by
      2.9-6.8% in the nucleotide sequence level, resulting in 206 nucleotide and 54
      amino acid substitutions which were observed in only Dg1062 isolate relative to
      the consensus sequences of other strains. Despite the variations of amino acids
      over the full genome including HN gene, it might be considered that this isolate
      have no significant variations in the antigenic sites. This result is the first
      report of full-length genome of genotype I strain and provides an overview on the
      diversity of genetic characteristics of circulating mumps virus.

PMID- 14976421
TI  - Isolation, molecular characterisation and genome sequence of a bacteriophage
      (Chp3) from Chlamydophila pecorum.
AB  - Chlamydiae are obligate intracellular pathogens that have a unique developmental
      cycle. Thirty nine viable isolates representing all nine currently recognised
      chlamydial species were screened by immunofluorescence with a cross-reacting
      chlamydiaphage monoclonal antibody. A novel chlamydiaphage (Chp3) was detected in
      C. pecorum, a chlamydial species not previously known to carry bacteriophages.
      Chp3 belongs to the Microviridae, members of this virus family are characterised
      by circular, single-stranded DNA genomes and small T = 1 icosahedral capsids.
      Double-stranded replicative form Chp3 DNA was purified from elementary bodies and
      used as a template to determine the complete genome sequence. The genome of Chp3
      is 4,554 base pairs and encodes eight open reading frames organised in the same
      genome structure as other chlamydiaphages. An unrooted phylogenetic tree was
      constructed based on the major coat proteins of 11 members of the Microviridae
      and Chp3. This showed that the Microviridae are clearly divided into two discrete
      sub-families; those that infect the Enterobacteriaceae e.g. OX174 and the
      bacteriophages that infect obligate intracellular bacteria or mollicutes
      including SpV4 (Spiroplasma melliferum), OMH2K (Bdellovibrio bacteriovorus) and
      the chlamydiaphages. Comparative analyses demonstrate that the chlamydiaphages
      can be further subdivided into two groupings, one represented by Chp2/Chp3 and
      the other by OCPG1/OCPAR39.

PMID- 14976423
TI  - The molecular mysteries underlying P-glycoprotein-mediated multidrug resistance.

PMID- 14976422
TI  - Expression of recombinant envelope protein of Japanese encephalitis virus YL
      strain in Escherichia coli possesses hemagglutination activity.
AB  - The nucleotide sequence of glycoprotein E of YL vaccine strain was cloned,
      sequenced and expressed in E. coli. Phylogenetic analysis of envelope (E) amino
      acid sequences of 18 JEVs in GenBank showed that the vaccine strain YL closer to
      the virulent strain HVI which is a Taiwanese isolate. We found only two amino
      acid mutations (K-138 and G-389) of E protein might lead viral attenuation in YL.
      In this study, we used pRSET vector system to construct three recombinant
      plasmids (pRSET/F1R1, pRSET/F2R2 and pRSET/F1R2), which encoded and expressed
      different or overlapping amino acid region of E protein. The antigenicity and
      hemagglutination activity of these recombinant proteins were examined by western
      blotting and hemagglutination test, respectively. Our results demonstrated that
      the recombinant protein of pRSET/F1R2 possesses predominant antigenicity and
      hemagglutination activity.

PMID- 14976424
TI  - Targeting of radio-isotopes for cancer therapy.
AB  - Treatment of patients with therapeutic monoclonal antibodies (mAbs) such as
      rituximab (Rituxan), an anti-CD20 mAb, or trastuzumab (Herceptin), an anti-HER2
      mAb, have shown efficacy in clinical trials and have gained approval from the
      Food and Drug Administration (FDA). Mylotarg, an anti-CD33 mAb conjugated with
      the antibiotic calicheamicin has proven efficacious in the treatment of patients
      with acute myeloid leukemia and has also received FDA approval. However, the use
      of radionuclides to either augment inherent activity or to exploit the specific
      targeting properties has been a major development in mAb therapeutics.
      Radionuclide- bearing mAbs have recently been approved by the FDA; Zevalin, an
      anti-CD20 mAb armed with (90)Y and Bexxar, an anti-CD20 mAb armed with (131)I.
      This overview presents some background and some of the strategies pertaining to
      radiolabeled monoclonal antibody therapies with a focus on experiences reported
      for radiolabeled mAbs as evaluated in clinical trials.

PMID- 14976425
TI  - Transgenic mouse models provide new insights into the role of p63 in epidermal
      development.
AB  - The epidermis is a stratified epithelium which provides a barrier between the
      organism and the environment protecting it from dehydration and pathogenic
      insult. A gene essential for development of the epidermis and other stratified
      epithelia is the transcription factor p63. The p63 gene is transcribed into
      isoforms that contain (TA) or lack (DeltaN) a transactivation domain. Of these
      isoforms, only TAp63 isoforms are expressed in the uncommitted surface ectoderm,
      while DeltaNp63 isoforms are expressed after the surface ectoderm has committed
      to a stratification program. Consistent with these embryonic expression profiles,
      we found that TAp63alpha functions as the master switch for initiation of
      epithelial stratification. Furthermore, TAp63alpha induces proliferation and
      inhibits terminal differentiation. This inhibition is overcome by the subsequent
      expression of DeltaNp63alpha which, in this context, acts as a dominant-negative
      molecule and allows basal keratinocytes to withdraw from the cell cycle and
      commit to terminal differentiation. These data demonstrate that TA- and DeltaNp63
      isoforms have fundamentally different roles during epidermal development and
      provide new insight into the molecular events required for normal epidermal
      morphogenesis.

PMID- 14976426
TI  - Cancer research: the art of creative thinking.

PMID- 14976427
TI  - Regulation of translation and cancer.
AB  - One of the effects of oncogenic signaling appears to be differentiated
      recruitment of mRNA's to ribosomes. The mRNA's so affected frequently encode
      proteins involved in growth regulation cell-cell interaction. These functions are
      critical for both cancer and development, potentially suggesting that the normal
      role of differential translation may be during development. It is not known
      whether this effect is sufficient to induce cancer from cells with an initial non
      neoplastic gene expression profile.

PMID- 14976428
TI  - A new role for C/EBPbeta in acute promyelocytic leukemia.
AB  - The differentiating properties of retinoic acid (RA) have been used beneficially
      for the treatment of Acute Promyelocytic Leukemia (APL) for more than a decade.
      However, the molecular mechanisms of how RA induces APL cell differentiation are
      still poorly understood. In our previous work, we provided a novel mechanism to
      explain the unique sensitivity to RA of APL cells. We proposed that C/EBPbeta is
      an ATRA-dependent PML/RARA target gene and that its activation is critical during
      ATRA-induced differentiation of APL cells. Here, I discuss how C/EBPbeta could be
      an important gene in APL pathogenesis.

PMID- 14976429
TI  - Inhibition of the p53-hdm2 interaction with low molecular weight compounds.
AB  - The hdm2 protein, upon binding to p53, inhibits its tumor suppressor activity.
      The inhibition of the p53-hdm2 interaction represents therefore a new therapeutic
      strategy to activate wild type p53 in tumors. Potent low molecular weight
      compounds inhibiting this protein-protein interaction, which are active in vivo,
      have just been identified. This offers new perspectives and hopes in this
      research area.

PMID- 14976430
TI  - Signaling, drugs and apoptosis of myeloma cells.

PMID- 14976431
TI  - Monoubiquitination: the signal for p53 nuclear export?
AB  - The ubiquitin-proteasome pathway has become an increasingly important regulatory
      mechanism for protein function. Countless proteins are degraded by the addition
      of polymeric ubiquitin chains, but more recently, monoubiquitination has emerged
      as a mechanism for regulatory functions other than proteasomal degradation.
      Monoubiquitination acts as a signal in nuclear export for the tumor suppressor
      protein p53. Different levels of Mdm2 are capable of inducing both mono- and
      polyubiquitination in a dosage dependent manner, thus determining p53's fate. Our
      findings demonstrate monoubiquitin-mediated protein trafficking can be expanded
      to nuclear-cytoplasmic shuttling, and also imply similar scenarios may apply to
      other cellular factors.

PMID- 14976432
TI  - Expression and localization studies of hSDA, the human ortholog of the yeast SDA1
      gene.
AB  - The yeast SDA1 gene was reported to play a critical role in G(1) events and to be
      involved in 60S ribosome biogenesis. Although the basic cellular mechanisms
      appear conserved from yeast to man, the human genes may have more diversified
      functions. In this view we obtained the first experimental evidences about the
      human ortholog of the yeast SDA1, i.e., hSDA. The gene is localized at the
      chromosomal region 4q21 and encodes for a 627a.a. long protein highly homologous
      to the yeast Sda1. Subcellular localization experiments indicate that the human
      protein behaves similarly to nucleolar proteins involved in rRNA processing
      machinery but not in RNA PolI transcriptional events. hSda appears localized in
      the granular component of the nucleolus and in the nucleoplasm, which is
      consistent with a role in early-intermediate steps of ribosome biogenesis. hSDA
      appears preferentially expressed in fetal tissues, pinpointing its role during
      development. Different expression levels in different tumor cell lines might
      suggest that the gene is involved also in tumorigenesis. However our preliminary
      results indicate that hSDA does not behave like a proapoptotic gene and its
      involvement in tumorigenesis is still to be clarified.

PMID- 14976433
TI  - [Moraxella catarrhalis: an emerging respiratory pathogen].
AB  - In the past years Moraxella (Branhamella) catarrhalis has finally gained respect
      as a pathogen thanks to the many reports of its causal role. The intent of this
      review is to provide a critical evaluation of the intent of this review is to
      provide a critical evaluation of the microbiological features (taxonomy,
      diagnosis, virulence, epidemiology and drug resistance), clinical diseases and
      therapy of this microorganism

PMID- 14976434
TI  - [Enterococcal endocarditis: clinical and microbiological features of our series].
AB  - Of 81 cases of infectious endocarditis seen at our institution from 1988 to 1995,
      61 had positive culture (75%) and, of these, 10 (16%) were caused by enterococcal
      strains (9 by Enterococcus faecalis, 1 by Enterococcus faecium). The 10 cases
      consisted of 5 native valve endocarditis and 5 late prosthetic valve
      endocarditis. Median age of patients was 50 years (range 21-58); 6, were males.
      Diagnostic or surgical procedures on the abdomen, genito-urinary tract, or chest
      preceded the onset of fever in almost all cases. Nine enterococcal strains showed
      low-level resistance to aminoglycosides and one was highly resistant. Seven
      patients were treated with ampicillin and gentamicin and 2 with teicoplanin and
      gentamicin. The patient, whose infection was caused by an high gentamicin
      resistant E. faecalis, was treated with the combination of ciprofloxacin and
      cotrimoxazole chosen on the basis of the in vitro susceptibility tests.
      Congestive heart failure occurred in 4 patients and major embolic events in 3.
      All patients were cured; 4, with medical therapy alone and 6, with antimicrobials
      associated with surgical substitution of the valve. The data indicate that
      enterococcal endocarditis, when treated with appropriate antimicrobial regimens,
      associated with surgical treatment when necessary, has a very low mortality rate.
      The conventional treatment, -lactams plus gentamicin is usually effective.
      However, for high-level gentamicin-resistant strains alternative treatments must
      be selected on the basis of the in vitro susceptibility tests.

PMID- 14976435
TI  - [Prevalence of hepatitis C virus infection in different groups of selected
      populations].
AB  - The objective of this study to determine the prevalence of hepatitis C virus at
      Caltagirone (CT) among blood donors, health care workers, drug users,
      hemodialysis patients and thalassaemics. The identification of risk factors for
      HCV infection and liver function in HCV correlate hepatitis. Anti-hepatitis C
      virus antibodies were detected in 0.64% of blood donors, in 68.44% of drug users,
      in 58.55% hemodialysis patients and in 67.50% of thalassaemics. Drug abuse,
      haemodialysis, blood transfusions are the major risk factors for hepatitis C.

PMID- 14976436
TI  - [AIDS--TB complex in Guinea Bissau: an epidemiological updating].
AB  - In Guinea Bissau, West Africa's little country, since 1989 to 1995 June the first
      3091 patients with tuberculosis have been tested for HIV-1, and HIV-2 infections.
      During the first two years of epidemic surveillance the HIV-2 seroprevalence
      among tuberculotics was respectively 14.89% and 17.26%. Since 1991 it has been
      noticed besides an increase of seroprevalence for HIV-2 up to 20,27% in 1992, a
      constant increase for HIV-1 infection, associated or not with HIV-2. The Authors
      conclude that the epidemiologic pattern of Guinea Bissau is particularly
      interesting because in this country two epidemics (for HIV-1 and for HIV-2) have
      been followed since the beginning among tuberculotics allowing to study the
      natural history and epidemiologic evolution with particular accuracy.

PMID- 14976437
TI  - [Bacterial endocarditis in an infectious diseases department: our experience].
AB  - The infective endocarditis remains a serious disease. The microbiologic,
      immunologic and technologic researches have contributed to the diagnosis and cure
      of the disease. The Authors report the results on ten cases of infective
      endocarditis that came to their observation in the last five years. They
      emphasize the more important epidemiologic aspects, the role of the laboratory
      and instrumental results to define an early diagnosis and the best results about
      of the therapies used

PMID- 14976438
TI  - [Beta-haemolytic group A streptococcal acute pharyngo-tonsillitis in pediatric
      patients: a clinical and epidemiological study].
AB  - Authors compared the efficacy and safety of 10-day regimen of Cefaclor (CEC),
      oral suspension, at the dose of 25 mg/kg BID, and Amoxicillin/clavulanic acid
      (AMC), and Erythromycin (E) both given TID at the dose of 15 mg/kg in the
      treatment of proven group A beta hemolytic streptococcal pharyngo-tonsillitis. Of
      the 673 enrolled pediatric patients, 245 were selected and assigned to three
      groups of treatment (85 received CEC, 78 received AMC and 82 received E) and 217
      were evaluated for efficacy. Clinical evaluations were performed on days 5 and 10
      of treatment and 20 days after its completion (follow up). Before treatment, on
      treatment day 10 and at follow up throat swab cultures were performed. In
      evaluable patients the post-therapy clinical success and bacteriological
      eradication rate for CEC was 91.8% (68 of 74 evaluable patients); the rate for
      AMC and E were 90.5% (67/74) and 76.8% (53/69) respectively. At follow up
      bacteriological eradication was observed in 63 of 68 clinically cured patients
      (92.6%) in the CEC treatment group; in 64 of 67 (95.5%) in the AMC treatment
      group and in 49 of 53 (92.4%) in the E treatment group. Adverse events occurred
      in 24 of 217 (11.05%) treated patients and the incidence of side effects was
      lower in CEC group. In vitro sensitivity tests showed 37.9% of isolated SBEGA
      strains resistant to macrolides and 32% of SBEGA strains resistant to
      tetracycline. In our experience Cefaclor administered BID is as effective and
      more safe than Amoxicillin/clavulanic acid and more effective than Erythromycin
      both given TID.

PMID- 14976439
TI  - [Diagnosis of HCV infection by 3rd-generation ELISA in HCV-RNA positive
      hypertransaminasemic patients with 2nd-generation ELISA negative results].
AB  - To evaluate the improved sensitivity of 3rd-generation assays for the detection
      of ani-HCV antibodies in diagnosing cases of HCV infection, we have re-tested by
      3rd-generation ELISA test (ELISA-3) serum samples from immunocompetent patients
      with chronic hypertransaminasemia who were HCV-RNA positive but tested negative
      with 2nd-generation ELISA (ELISA-2). Out of 21 HCV-RNA positive/ELISA-2 negative
      samples, 3 (14.3%) were ELISA-3 positive. Among the ELISA-3 reactive samples, two
      were indeterminate by RIBA-3 (one was reactive with c1 00 and the other with
      c22), and one was negative. These results demonstrate that even in the clinical
      setting ELISA-3 improves the diagnosis of HCV infection. The improvement seems to
      be related to a better reactivity of HCV peptides rather than to the inclusion of
      the new determinant NS5. However, the sensitivity of the tests for the detection
      of anti-HCV antibodies remains to be improved.

PMID- 14976440
TI  - [Angioneurotic edema associated to clarithromycin therapy].

PMID- 14976441
TI  - [About "social" history of malaria].

PMID- 14976442
TI  - Off-pump coronary artery bypass grafting: simple concept but potentially sublime
      scientific value.
AB  - This review discusses the available scientific evidence of the physiological
      changes and clinical outcomes with off-pump coronary artery bypass grafting. Off
      pump coronary artery bypass grafting is more technically demanding, and its
      prognostic advantage has not been clearly elucidated. This paper examines the
      evolution of off-pump coronary artery bypass grafting and the technical
      challenges of 'bypassing' the cardiopulmonary bypass machine. A search of the
      Medline database of English-language literature yielded a huge number of articles
      from which those relating to physiological and biochemical changes, and clinical
      outcomes of coronary artery bypass grafting were selected for this review. There
      are few prospective randomized trials, mostly studying physiological and
      biochemical changes, and assessing specific clinical outcomes. Avoidance of
      cardiopulmonary bypass results in a significantly reduced systemic inflammatory
      response. Myocardial, renal and neurological functions, amongst others, are
      better preserved. A rapid advance in beating heart surgery technology occurred in
      the past 5 yrs enabling off-pump multivessel coronary bypass grafting to be
      performed with relative technical ease, thereby offsetting the propensity to
      incomplete revascularization which can be a major setback. The clinical outcome
      of patients with varying surgical risks who have off-pump coronary artery bypass
      grafting are comparable to those who have surgical revascularization with
      cardiopulmonary bypass. With the technical challenges of off-pump coronary bypass
      grafting surmounted, the simple concept of avoiding cardiopulmonary bypass can
      yield impressive results that would help to establish the routine use of this
      technique for myocardial revascularization.

PMID- 14976443
TI  - The role of neuroimaging in the investigation of patients with single seizures,
      febrile seizures, or refractory partial seizures.
AB  - Seizures are a symptom of an underlying brain disorder. The accurate
      identification of the nature of the disease generating the seizures facilitates
      treatment and can prevent further brain damage. The understanding of the
      physiopathology underlying the seizures has been greatly enhanced by the
      possibility to examine these patients with advanced forms of neuroimaging. Among
      different forms of investigation, neuroimaging techniques play a major role in
      diagnosis and decision-making in the care of patients with epilepsy. We review
      the contributions of current methods of imaging in the investigation of patients
      with single seizures, febrile seizures or refractory seizures, assessing the
      practical aspects, benefits, and operational costs of various neuroimaging
      techniques. The focus is on MRI, which is the imaging modality of choice for
      outpatient investigation. We also assessed the benefits from CT scans, which
      remain the first option for emergency seizure assessment. The aim was to evaluate
      how the structural, functional and metabolic information provided by modern
      techniques of neuroimaging decreases the need for additional investigation and
      speeds the management of these epileptic disorders. This makes it possible to
      accurately define the location and the nature of the epileptogenic lesions
      related to seizures.

PMID- 14976444
TI  - Autism as early expression of catatonia.
AB  - BACKGROUND: Reports indicate that catatonia often occurs in autism. The
      association lacks a conceptual basis. Modern classificatory schemes define autism
      and catatonia separately and are not conducive to study areas of overlap. The
      exploration of the relation between autism and catatonia may be important because
      autism is increasingly recognized but effective treatments are lacking.
      Catatonia, on the other hand, is thought to be treatable, but is poorly
      recognized. MATERIAL/METHODS: The literature on autism and catatonia are reviewed
      to identify areas of overlap. A hypothesis is formulated that, in some cases,
      autism may the early expression of catatonia. RESULTS: Several areas of overlap
      between autism and catatonia are found. Catatonic symptoms are common in autism.
      Effects of anti-catatonic treatments on autistic symptoms are unknown. Abnormal
      gamma-aminobutyric acid (GABA) function has been implicated in both disorders.
      Neuroimaging studies show small cerebellar structures in both disorders. There is
      genetic evidence that susceptibility genes for autism and catatonia are located
      on the long arm of chromosome 15. Differences between autism and catatonia of age
      of-onset, symptoms, and illness course, do not exclude a common genetic etiology.
      CONCLUSIONS: Focused research is needed to further evaluate the phenomenological,
      biological, and genetic overlap between autism and catatonia and to test the
      hypothesis that a subgroup of autism is early-onset catatonia.

PMID- 14976445
TI  - Gastrectomy does not influence the levels of aminotransferases, total protein and
      albumin in humans.

PMID- 14976446
TI  - Reliability of the rapid bedside whole-blood quantitative cardiac troponin T
      assay in the diagnosis of myocardial injury in patients with acute coronary
      syndrome.
AB  - BACKGROUND: A rapid bedside whole-blood quantitative cTnT assay has recently been
      developed. We evaluated the reliability of this test for the diagnosis of
      myocardial injury in patients with acute coronary syndrome (ACS).
      MATERIAL/METHODS: Whole-blood cTnT levels were measured in 96 patients with ACS
      using the Roche Cardiac Reader(R) rapid bedside assay device, and the results
      were compared with serum cTnT levels in the same patients measured by the Roche
      Elecsys(R) Immunoanalyzer. There were 50 patients with clinical evidence of
      myocardial injury and 56 without. RESULTS: From the qualitative point of view
      (reporting negative or positive tests), the results of the rapid bedside tests
      were identical to those obtained by the serum immunoanalyzer. From quantitative
      the point of view, the rapid bedside tests could not measure exact values below
      0.1 ng/ml (reported negative) or above 2.0 ng/ml (reported >2.0). The
      measurements made by the rapid bedside tests within the range of 0.1 to 2.0 ng/ml
      correlated well with those of the serum immunoanalyzer (Cardiac Reader(R)
      cTnT=0.61, Elecsys(R) cTnT+0.12; r=0.88), but their mean values were
      significantly lower (1.20I0.71 vs. 1.41I1.03, p=0.0007). CONCLUSIONS: The rapid
      bedside cTnT assay correlates well with immunoanalyzer measurements between the
      values of 0.1 and 2.0 ng/ml. However, they tend to give significantly lower
      values and fail to give exact values below 0.1 and above 2.0 ng/ml, which may
      affect their performance in monitoring and managing patients with ACS, and limit
      their use in predicting outcome.

PMID- 14976447
TI  - External Dacryocystorhinostomy: outcomes after the introduction of two new
      forceps and transnasal endoscopy.
AB  - BACKGROUND: There are few lacrimal surgeons in the field of clinical
      Ophthalmology, while the number of patients with an obstruction of tear duct
      increases. The success rate for the external dacryocystorhinostomy (DCR)
      procedure is approximately 90%. The outcome of external DCR using two new forceps
      and postoperative transnasal endoscopy was studied. MATERIAL/METHODS: 93
      consecutive patients (100 cases) underwent external DCR. Two new forceps (a DCR
      slide forceps and a cleaning forceps in the nasal cavity) were used, and
      transnasal endoscopic examination postoperatively was done. The relatively small
      cutaneous incision (12-15 mm) was done. Two new forceps were used during and
      after the DCR procedure. RESULTS: All the cases showed round or oval ostia and
      patency on irrigation. Some amount of discharge adherent to the STs was observed
      in each case within one week after the external DCR procedure. CONCLUSIONS: The
      transnasal endoscopic examination performed postoperatively and the use of the
      two new forceps were of value for increasing the success rate of external DCR.

PMID- 14976448
TI  - The metabolic effects of insulin and rosiglitazone combination therapy in Chinese
      type 2 diabetic patients with nephropathy.
AB  - BACKGROUND: Few studies have examined the efficacy and safety of
      thiazolidinedione use in patients with diabetic nephropathy. Our goal was to
      examine the metabolic effects and tolerability of combination therapy with
      rosiglitazone and insulin in type 2 diabetic patients with nephropathy and renal
      failure. MATERIAL/METHODS: We evaluated the metabolic effects and tolerability of
      rosiglitazone as an add-on therapy to insulin in 12 Chinese type 2 diabetic
      patients (5 males and 7 females) with nephropathy and renal impairment. The mean
      age of these patients was 65+/-8.3 years, and the mean duration of disease was
      16.5+/-8.6 years. The initial daily dosage of rosiglitazone, 2 mg daily, was
      increased to 4 mg if their fasting plasma glucose concentrations were above 10
      mmol/L after 4 weeks. RESULTS: Over a mean period of 15.5 months, HbA1c improved
      significantly following the addition of rosiglitazone, from 8.57+/-1.42% to
      7.48+/-1.3% (p=0.01). There was a trend towards improved lipid profile with this
      combination therapy, but it was not statistically significant. There was no major
      adverse events except for minimal weight gain (71.7+/-13.6 kg vs 73.9+/-13.1 kg,
      p=0.08). CONCLUSIONS: Combination therapy with rosiglitazone and insulin has
      beneficial metabolic effects and is generally well tolerated in type 2 diabetic
      patients with nephropathy and mild to moderate renal failure.

PMID- 14976449
TI  - Gabexate mesilate and heparin responsiveness in coronary patients.
AB  - BACKGROUND: Heparin responsiveness in patients undergoing coronary operations
      changes depending on many individual factors. Reduced sensitivity to heparin is a
      common feature and may determine a difficult intraoperative anticoagulation. The
      aim of this study was to determine the effectiveness of a novel serine proteases
      inhibitor (gabexate mesilate) in increasing heparin responsiveness.
      MATERIAL/METHODS: 20 patients undergoing coronary operations with cardiopulmonary
      bypass were studied with respect to their heparin responsiveness. This was
      measured using individual dose/response tests with a heparin monitoring system
      before and after a 10-minute intravenous infusion of 2 mg.kg-1.h-1 of gabexate
      mesilate, a direct inhibitor of factor Xa, thrombin, kallikrein, and other serine
      proteases. The complete test was performed before initiating the surgical
      maneuvers. RESULTS: At each heparin concentration, gabexate mesilate produced a
      significant prolongation of the kaolin-activated clotting time. The heparin
      responsiveness (seconds.IU-1.ml-1) in terms of activated clotting time
      significantly (p=0.007) increased from the baseline of 68.1+/-13.8 to 74.7+/-16.1
      during infusion, and the heparin loading dose (IU/kg) required to reach the
      target activated clotting time of 480 seconds significantly (p=0.009) decreased
      from the baseline of 290+/-82.3 to 260+/-77.6 during gabexate mesilate infusion.
      CONCLUSIONS: Gabexate mesilate significantly increases individual heparin
      responsiveness in coronary patients. Its use in the treatment of patients with a
      reduced sensitivity to heparin may support or replace the conventional
      therapeutic approach based on fresh frozen plasma or purified antithrombin.

PMID- 14976450
TI  - A comparative evaluation of the effects of MMR immunization and mercury doses
      from thimerosal-containing childhood vaccines on the population prevalence of
      autism.
AB  - BACKGROUND: The purpose of the study was to evaluate the effects of MMR
      immunization and mercury from thimerosal-containing childhood vaccines on the
      prevalence of autism. MATERIAL/METHODS: Evaluations of the Biological
      Surveillance Summaries of the Centers for Disease Control and Prevention (CDC),
      the U.S. Department of Education datasets, and the CDC's yearly live birth
      estimates were undertaken RESULTS: It was determined that there was a close
      correlation between mercury doses from thimerosal--containing childhood vaccines
      and the prevalence of autism from the late 1980s through the mid-1990s. In
      contrast, there was a potential correlation between the number of primary
      pediatric measles-containing vaccines administered and the prevalence of autism
      during the 1980s. In addition, it was found that there were statistically
      significant odds ratios for the development of autism following increasing doses
      of mercury from thimerosal-containing vaccines (birth cohorts: 1985 and 1990
      1995) in comparison to a baseline measurement (birth cohort: 1984). The
      contribution of thimerosal from childhood vaccines (>50% effect) was greater than
      MMR vaccine on the prevalence of autism observed in this study. CONCLUSIONS: The
      results of this study agree with a number of previously published studies. These
      studies have shown that there is biological plausibility and epidemiological
      evidence showing a direct relationship between increasing doses of mercury from
      thimerosal-containing vaccines and neurodevelopmental disorders, and measles
      containing vaccines and serious neurological disorders. It is recommended that
      thimerosal be removed from all vaccines, and additional research be undertaken to
      produce a MMR vaccine with an improved safety profile.

PMID- 14976451
TI  - Influence of coronary artery bypass grafting on QT dispersion.
AB  - BACKGROUND: Abnormal dispersion of the QT interval (QTd), measured as the
      interlead variability of QT, reflects an inhomogeneity of ventricular action
      potentials. In this study we observed both short- and long-term influences of
      coronary artery bypass grafting (CABG) on rest and exercise QTd in 64 male
      patients, having a mean age of 54+/-10 years, with coronary heart disease.
      MATERIAL/METHODS: QTd was measured as the difference between QT maximum and
      minimum from 12 leads on an averaged ECG (25 mm/s). QTd and QTdc were measured at
      rest and at peak exercise during symptom-limited treadmill exercise (ET), which
      was performed before, 6 months after, and 2 years after CABG. RESULTS: There was
      a significant reduction in rest QTd from before CABG to 6 months and 2 years
      after (60+/-20 ms vs. 43+/-14 ms and 45+/-13 ms, respectively; p<0.001).
      Similarly, there was a significant reduction in peak QTd from before CABG to 6
      months and 2 years after (66+/-22 ms vs. 38+/-11 ms and 36+/-11 ms, respectively;
      p<0.001). Two years after CABG, 17 patients had a recurrence of angina and ET
      provoked chest pain and/or >2 mm ST depression. The resting values did not
      distinguish patients with ischemia from nonischemic ones. In patients with
      ischemia, ET provoked an increase in QTdc. CONCLUSIONS: Rest and exercise QTd is
      significantly reduced after CABG. It seems that the measurement of QT dispersion
      during ET can be helpful in distinguishing patients with a recurrence of
      ischemia.

PMID- 14976452
TI  - The presence and structure of circulating immune complexes in patients with
      prostate tumors.
AB  - BACKGROUND: The detection, measurement and characterization of circulating immune
      complexes (CICs) in tumor patients has shown both good and poor correlation with
      progression of the disease. The origin of the antigens making up the immune
      complexes in the sera of the cancer patients examined is unknown. They are
      perhaps antigens specific to the cancer's progress. MATERIAL/METHODS: The levels
      and molecular weights of circulating immune complexes were estimated in the sera
      of 48 patients with adenocarcinoma (grades G-1, G-2, and G-3) and 21 patients
      with benign prostate hyperplasia (BPH) by means of the polyethylene glycol (PEG)
      precipitation test. RESULTS: The results were compared with those of a group of
      45 healthy blood donors. Elevated levels of CICs were observed in 66.7% of the
      patients with adenocarcinoma and in 38% of those with BPH. No seropositivity for
      CICs was observed in the control group. Increased seropositivity for CICs was
      observed in patients with the highness grade of adenocarcinoma: the proportion of
      seropositive patients in the group of patients with the G-1 phase of disease was
      50%, with G-2 75%, and with G-3 71.3%. The molecular weights of the CIC proteins
      were determined by SDS/PAGE. The serum CICs of both BPH and prostate cancer
      patients consisted of proteins absent in the CICs of the sera of healthy persons.
      CONCLUSIONS: Determination and analysis of atypical proteins in CICs resulting
      from carcinogenesis may by useful in improving the diagnosis.

PMID- 14976453
TI  - Incidence and clinical characteristics of second malignant neoplasms in children:
      a multicenter study of a polish pediatric leukemia/lymphoma group.
AB  - BACKGROUND: The development of second malignant neoplasms (SMNs) in patients
      receiving chemotherapy and radiation therapy for primary cancers is one of the
      limitations to the quality and length of survival. The present study was
      undertaken to examine various characteristics of children who developed SMNs
      following successful therapy for primary leukemia or Hodgkin's disease (HD).
      MATERIAL/METHODS: A total of 3252 children with various forms of leukemia and 849
      children with HD treated between, 1970-1997 at 7 pediatric centers of the Polish
      Pediatric Hematology/Oncology Group and subsequently followed-up entered the
      study. A second malignancy was diagnosed in 36 of these children. RESULTS: Of the
      3252 patients diagnosed as having acute leukemia during this period, 16 developed
      SMNs (estimated frequency 0.49%). SMNs developed in 20 of the 849 children
      treated for HD (2.36%). The most frequent SMNs were soft tissue sarcoma and
      thyroid carcinomas, mainly following Hodgkin's disease. Other tumors occurred at
      about the same frequencies in both groups. The interval from the end of initial
      treatment to diagnosis of an SMN ranged from 2 years 7 months to 17 years 6
      months, with a median of 7 yrs 4 mo. for acute lymphoblastic leukemia (ALL)
      patients and 10 years for children with HD. The estimated accumulated risk of SMN
      following acute leukemia is 0.95% at 15 years and, for HD, 5.1% at 20 yrs and 7%
      at 25 yrs. CONCLUSIONS: Children who have been successfully treated for one
      cancer have a higher than expected incidence of additional tumors.

PMID- 14976454
TI  - The exposure to cadmium, lead and mercury from smoking and its impact on renal
      integrity.
AB  - BACKGROUND: Human beings are exposed to cadmium (Cd), lead (Pb) and mercury (Hg)
      from cigarette smoking. Whether this exposure is associated with nephrotoxicity
      is unknown. MATERIAL/METHODS: A total of 68 adult males were included in this
      study. The studied population was grouped into those who are smokers (n=35) and
      those who had never smoked (n=33). Cd, Pb and Hg were determined in the blood,
      urine, hair and nails to assess the extent of exposure to these metals. Urinary
      excretion of b2-microglobulin (b2M), N-acetyl-b-D-glucosaminidase (NAG), g
      glutamyltransferase (g-GT) and alkaline phosphatase (ALP) were determined as
      markers of tubular damage. Albuminuria was determined as a marker of glomerular
      damage. Serum levels of creatinine, b2M, and blood urea nitrogen (BUN) were
      determined to assess glomerular filtration. RESULTS: The Cd level in blood and Pb
      levels in blood and hair were significantly higher in the smokers than non
      smokers. Blood levels of Cd and Pb correlated significantly with the smoking
      index (an indicator for the degree of smoking) in the smokers group. The studied
      markers of kidney damage neither elevated among the smokers nor correlated with
      the exposure indices of these metals. CONCLUSIONS: Smokers are exposed to Cd and
      Pb. This exposure is not high enough to produce nephrotoxicity. However, it may
      incite signs of nephrotoxicity in the presence of risk factors for kidney
      diseases.

PMID- 14976455
TI  - Clinical course of insular thyroid carcinoma.
AB  - BACKGROUND: To present the clinical picture and outcome of poorly differentiated
      insular-type thyroid carcinoma (ITC) compared with papillary thyroid carcinoma
      (PTC) in a Mexican population in order to demonstrate their different biological
      behavior. MATERIAL/METHODS: Retrospective, transversal study comparing ITC (G1)
      with PTC (G2). Assessed variables were: age, gender, size of tumor, previous
      history of thyroid disease, and outcome. The recurrence/death risk was
      established according to the MACIS, De GROOT, and AMES classifications.
      Statistical analysis was made by means of central tendency measures, the Kaplan
      Meier method, Cox-Mantel's log-rank, Student's t, and chi-square tests. RESULTS:
      Both groups were classified based on a high or low risk for thyroid neoplasms. G1
      had 13 patients, tumor volume was 78 cm3, 7 cases presented metastases at the
      time of admittance, five had antecedents of goiter. Average follow-up time was 23
      months. G2 had seventy-one patients, tumor volume was 42 cm3, and follow-up time
      of 44 months. Kaplan-Meier revealed a lower survival in Group 1 than Group 2,
      statistically significant by the Cox-Mantel log-rank test. A significant
      statistical difference existed regarding survival and the presence of metastases:
      G1 (61%) and G2 (53.8%). No statistical difference was found between tumor size.
      CONCLUSIONS: ITC is more aggressive than PTC. It occurs in the 6th decade of
      life, with antecedents of long-standing goiter, and has a high recurrence,
      metastasis and mortality frequency.

PMID- 14976456
TI  - Familial variables as predictors of psychological maladjustment in Lithuanian
      children with phenylketonuria.
AB  - BACKGROUND: Children with phenylketonuria of early onset under continuous
      treatment are considered at higher risk for psychological maladjustment than
      children without other chronic diseases. The aim of the present study was to
      evaluate the psychological adjustment of Lithuanian children with treated
      phenylketonuria and analyze it in the context of the psychological adjustment of
      their parents. MATERIAL/METHODS: The parents of 37 early-treated children (age 4
      14 years old) with phenylketonuria and of 37 matched controls were asked to fill
      out the Child Behavior Checklist and questionnaire on stress coping strategies.
      Parents of children with phenylketonuria answered a questionnaire on reactions to
      the child's disease and its impact on the family. RESULTS: Lithuanian children
      with treated phenylketonuria have significantly more emotional and behavioral
      problems than healthy controls. They are more withdrawn, anxious/depressed, have
      more social and attention problems. The higher rates of internalizing and total
      problems are related to parental maladjustment (feelings of guilt and anger)
      together with maladaptive (emotional) everyday stress coping strategies. These
      last two factors promote overindulging the child, which is also a predictor of
      psychological maladjustment in children with phenylketonuria. CONCLUSIONS: The
      already existing organic vulnerability may account for the greater susceptibility
      of children with phenylketonuria to psychological risk factors, as for example
      parental inability to cope adequately with everyday stress related to the demands
      of disease and its treatment.

PMID- 14976457
TI  - The effects of long meditation on plasma melatonin and blood serotonin.
AB  - BACKGROUND: The benefits of meditation are well documented, but the biochemical
      mechanisms have not been fully identified. One effect mechanism may be via
      influence on neurotransmitters. MATERIAL/METHODS: Therefore, plasma melatonin and
      blood serotonin concentrations were measured before and after one hour of
      meditation in advanced male meditators (n=27, mean age 46 years). They were
      compared with a matched reference group (n=29, mean age 43 years) who rested for
      one hour. In the meditators, melatonin and serotonin from before and after three
      consecutive hours of meditation were also compared. RESULTS: Initially, the
      median melatonin level was 4.9 pg/ml-1 in the meditators and 3.1 pg/ml-1 in the
      reference group (p<0.01). After one hour of practice, melatonin had decreased to
      a median of 3.4 pg/ml-1 in the meditators (p<0.0001), but was unchanged in the
      reference group. After three hours of meditation, melatonin had declined further
      in the meditators. After one hour of practice, serotonin concentrations decreased
      in both the meditators and the reference group (p<0.01). CONCLUSIONS: The
      findings suggest that advanced meditators have higher melatonin levels than non
      meditators. Melatonin decreases during long meditation, a finding the study does
      not explain. Serotonin declines after both one-hour meditation and rest,
      indicating that serotonin may be a marker of general rest and not meditation
      specific relaxation.

PMID- 14976458
TI  - High levels of troponin T are associated with ventricular remodeling and adverse
      in-hospital outcome in heart failure.
AB  - BACKGROUND: Heart failure progression is associated with ventricular remodeling
      and ongoing myofibrillar degradation. We hypothesized that myocardial damage,
      detected by high levels of troponin T, would correlate with echocardiographic
      measurements of left ventricular remodeling and worse in-hospital course in
      decompensated heart failure. MATERIAL/METHODS: 159 patients with decompensated
      heart failure without acute coronary event were included. A troponin T value >0.2
      ng/ml in samples taken 6, 12 or 24 hours after admission was considered abnormal.
      RESULTS: High troponin T levels were identified in 24 patients (15%) (Group 1).
      Mean age for group 1 was 65.9 vs. 63.7 years in patients with troponin T<0.2
      (Group 2) (p=ns). Ischemic etiology in groups 1 and 2 was found in 58.3 and 38.5%
      (p=0.07). Two-dimensional echocardiograms in groups 1 and 2 revealed higher left
      ventricular diameters, diastolic (61.7+/-10 vs. 56.9+/-10.3 mm, p=0.041) as well
      as systolic (49.4+/-13.5 vs. 42.0+/-12.0 mm, p=0.012), and lower ejection
      fraction (30.1+/-14 vs. 39.0+/-17.7%, p=0.03). Incidence of combined end point of
      death or refractory heart failure was 20.8 and 3.7% in groups 1 and 2 (p=0.007;
      OR=6.8; CI95%=1.5-31.2). In a multiple regression model, a history of infarction
      and chronic obstructive pulmonary disease, tissue hypoperfusion, radiographic
      pulmonary edema, and high troponin T levels emerged as the independent
      predictors. CONCLUSIONS: High troponin T levels were found in 15% of patients
      with acute exacerbation of heart failure; this finding was independently
      associated with worse prognosis. Echocardiograms suggested that more severe
      ventricular remodeling is one subjacent mechanism related with biochemically
      detected myocardial injury in this setting.

PMID- 14976459
TI  - Relations between von Willebrand factor, markers of oxidative stress and
      microalbuminuria in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: to assess the relations among plasma levels of von Willebrand factor
      (vWf), microalbuminuria and markers of oxidative stress in patients with type 2
      diabetes mellitus. MATERIAL/METHODS: We studied 10 healthy subjects without
      microalbuminuria or history of coronary artery disease (CAD) and 30 patients with
      type 2 diabetes mellitus who were classified into three groups, each including 10
      patients of matched age and sex; group 1: patients without microalbuminuria or
      history of CAD; group 2: patients with microalbuminuria and no history of CAD,
      and group 3: patients with microalbuminuria and history of CAD. All subjects
      underwent laboratory measurements of vWf, albumin excretion rate (AER),
      malondialdehyde, vitamin C, reduced glutathione and C peptide. RESULTS: vWf was
      elevated in patients with type 2 diabetes mellitus compared with control
      subjects. However, levels were higher in patients with than without
      microalbuminuria and in patients with than without a history of CAD (96+/-12,
      124+/-7, 149+/-9, 175+/-7 in the control subjects and the diabetic patients'
      groups respectively). There was a positive correlation between vWf and AER, MDA
      and C- peptide (r=0.91, 0.98, 0.96, p<0.0001) and a negative correlation between
      vWf and both vitamin C and reduced glutathione (r=-0.59 and -0.62 respectively,
      p<0.001). CONCLUSIONS: vWf levels are elevated in patients with type 2 diabetes
      mellitus, particularly in the presence of microalbuminuria and history of CAD.
      vWf levels are associated with markers of increased oxidative stress and
      therefore reflect the severity of biochemical abnormalities, which contribute to
      diabetic vascular disease.

PMID- 14976460
TI  - Normalization of peripheral blood cell composition by lactoferrin in
      cyclophosphamide-treated mice.
AB  - BACKGROUND: Cyclophosphamide (CP) is used in the treatment of autoimmune
      disorders and leukemia. The compound induces severe leuko- and neutropenia.
      Lactoferrin (LF) is a protein which plays a role in the innate immunity. In this
      study we evaluated the usefulness of LF in reversing CP-induced lympho- and
      neutropenia in mice. MATERIAL/METHODS: CBA mice were treated with CP (350 mg/kg
      body weight, intraperitoneally) and given LF as a 0.5% addition to drinking
      water. Alternatively, LF was administered orally (seven doses, 1 mg each) on
      alternate days following CP injection. Control groups received CP or LF only.
      Blood samples were taken before treatment and on days 4, 8, 15 and 22 following
      CP injection to determine leukocytosis and cell types in blood smears. RESULTS:
      Mice treated with CP showed severe leukopenia, strong eosinophilia (day 4), and
      an altered lymphocyte/neutrophil ratio (days 8-22). Treatment of mice with LF for
      21 days partially normalized the cell composition in CP-treated mice (increased
      percentage of lymphocytes and decreased eosinophil content). The content of
      leukocytes increased upon LF treatment on days 4, 8, 15 and 22 (by 36.8, 39.5, 72
      and 70.7%, respectively). More importantly, LF partly normalized the neutrophil
      and lymphocyte composition on day 22 (neutrophils: 29.2% in control mice, 50.6%
      in CP-treated, and 39.16% in CP/LF-treated; lymphocytes: 66.18% in control mice,
      35% in CP-treated and 48.8% in CP/LF-treated). Administration of LF alone did not
      change the cell numbers or composition. CONCLUSIONS: LF given orally to CP
      immunocompromised mice accelerates reconstitution of lymphopoiesis and
      myleopoiesis.

PMID- 14976462
TI  - Factors raising intracellular calcium increase red blood cell heterogeneity in
      density and critical osmolality.
AB  - BACKGROUND: In normal human blood, RBC volume (V), surface area (A) and
      hemoglobin content (H) exhibit Gaussian distributions with coefficients of
      variation (CV) of 10-15%. Strikingly narrower distributions are observed for
      their cell density (CV approximately 0.5%) and filterability (CV approximately 5
      7%). This implies that V is highly correlated with H and A. We hypothesize that
      the RBC is able to adjust its volume to parameters H and A. It is tempting to
      speculate that intracellular free calcium (Cai) is a mediator in this process,
      acting as an activator of the Gardos channel. We tested this hypothesis by
      experimentally varying Cai and measuring changes in RBC density and filterability
      distributions. MATERIAL/METHODS: Three different approaches were used to raise
      Cai: (i) RBCs were loaded with Ca2+ in the presence of the calcium ionophore
      A23187; (ii) RBCs were incubated with Ca2+ in the presence of 1.0 mM ortho
      vanadate; and (iii) the calcium pump was switched off by ATP depletion of RBCs.
      The density distribution of RBCs was determined by a phthalate technique. The
      distributions in filterability were obtained using a kinetic filtrometer.
      RESULTS: Whatever the approach used, the density and filterability distributions
      of treated RBCs broadened significantly in comparison with those of control
      cells. CONCLUSIONS: The results obtained suggest that (i) in vivo regulation of
      RBC volume is mediated by Cai and (ii) Cai probably depends on the A/V ratio,
      which determines the stress experienced by the RBC membrane in the circulation
      and, thereby, the calcium influx rate.

PMID- 14976461
TI  - Effects of poly(ADP-ribose) polymerase inhibition on inflammatory cell migration
      in a murine model of asthma.
AB  - BACKGROUND: Poly(ADP-ribose) polymerase-1 (PARP-1), a monomeric nuclear enzyme
      present in eukaryotes, plays a role in cell death, inflammatory mediator
      expression, and mononuclear cell recruitment in various experimental models of
      inflammation and reperfusion injury. Part of the molecular mechanism of this
      function involves the regulation of cytokine and chemokine production. Since
      chemokines are principal regulators of mononuclear and polymorphonuclear cell
      trafficking in asthma, we investigated the possibility whether PARP modulates
      chemokine production and cell recruitment in a murine model of asthma.
      MATERIAL/METHODS: We studied ovalbumin-sensitized mice challenged with a single
      dose of ovalbumin. RESULTS: PARP inhibition with the phenanthridinone-based PARP
      inhibitor PJ34 suppressed inflammatory cell migration. These effects were
      associated with downregulation of the CC chemokine MIP-1alpha, but not the CXC
      chemokine MIP-2. The production of TNF- alpha and IL-12, but not IL-5 or IL-13,
      was also suppressed by PARP inhibition. CONCLUSIONS: Our results demonstrate the
      pathogenetic role of PARP activation in a murine model of asthma. PARP
      selectively regulates the production of certain chemokines and cytokines in this
      experimental model, which may be responsible for some of the observed protective
      effects seen in the current murine asthma model.

PMID- 14976463
TI  - Is percutaneous implantation of a bovine venous valve in the inferior vena cava a
      reliable technique to treat chronic venous insufficiency syndrome?
AB  - BACKGROUND: To evaluate the feasibility and safety of percutaneous implantation
      of a balloon-expandable valved stent in the inferior vena cava. MATERIAL/METHODS:
      A valve harvested from a bovine jugular vein, preserved in glutaraldehyde and
      mounted in a stent, was evaluated in animals. Six lambs, weighing 30 to 40 kg,
      were included in the study. Under general anesthesia, a valved stent with its 18
      Fr delivery system was inserted through the right jugular vein, advanced, and
      delivered in the inferior vena cava. Hemodynamic and angiographic evaluations
      were performed prior to, immediately after, and two months after implantation.
      RESULTS: All valved stents were successfully implanted in the desired position.
      No early or late migration of the stent was noted in any animal. All valves were
      perfectly competent at the time of implantation. At 2 months, none of the valves
      were functional. The inferior vena cava was occluded at the site of valve
      insertion and collateral circulation was present in all animals. At autopsy, the
      valved stent was completely occluded. CONCLUSIONS: Valve implantation is feasible
      in the venous system through a percutaneous approach. The function of this valve
      in that position is limited by the absence of a high pressure gradient. Animal
      models and improvements in the device are mandatory before considering this
      technique as a reliable procedure to treat chronic venous insufficiency syndrome
      in humans.

PMID- 14976464
TI  - Diazoxide enhances adipose tissue protein kinase B activation and glucose
      transporter-4 expression in obese Zucker rats.
AB  - BACKGROUND: Attenuation of hyperinsulinemia in obese Zucker rats by diazoxide
      (DZ) enhanced insulin sensitivity and insulin-stimulated glucose uptake in
      isolated adipocytes. To determine if these metabolic effects are due to changes
      in glucose transporter (Glut)-4 gene products and intracellular signaling, we
      studied the effects DZ on adipose tissue Glut-4 gene products, insulin receptor
      substrate (IRS)-1, total and phosphorylated protein kinase B (PKB)/Akt.
      MATERIAL/METHODS: DZ (150 mg/kg per day) or vehicle (control) was administered to
      7-week-old female obese and lean Zucker rats for 6 weeks. RESULTS: While adipose
      Glut-4 mRNA levels from control obese and lean rats were similar, Glut-4 protein
      content was 60% lower in obese than lean animals (p<0.05). DZ treatment increased
      mRNA in both obese (1.4 fold) and lean (1.7 fold) animals compared to controls
      (p<0.05), which was associated with a 3.7 fold and a 1.4 fold increase in Glut-4
      protein content in DZ obese (p<0.01) and lean (p<0.05) rats, respectively. IRS-1
      protein expression was lower in obese compared to lean rats (p<0.01) and was
      enhanced in DZ-treated obese (p<0.02) and lean (p<0.05) rats. While the PKB/Akt
      protein levels were similar in both strains, obese had lower p-Akt levels than
      lean rats (p<0.01). DZ-treated obese and lean rats had higher levels of p-Akt
      than their controls (p<0.05). CONCLUSIONS: Chronic suppression of
      hyperinsulinemia in obese Zucker rats improved intracellular insulin signaling
      and Glut-4 gene expression, corresponding to enhanced glucose uptake in isolated
      adipocytes. The discrepancy between adipose tissue Glut-4 mRNA and protein
      content in response to DZ treatment suggests post-transcriptional regulatory
      effects resulting from enhanced metabolic efficiency of insulin action.

PMID- 14976465
TI  - Modifications of immunological and neuro-endocrine parameters induced by
      antiorthostatic bed-rest in human healthy volunteers.
AB  - AIM: Space flight has profound effects on immunological and neuroendocrine
      parameters. Microgravity plays a major role in the induction of these changes.
      The aim of the present study was the evaluation on ground of the effects induced
      by antigravitary posture on immune and neuroendocrine functions. METHODS: Eight
      healthy male volunteers (mean age 24+/-1 years) were maintained in antigravitary
      posture (-10 degrees) for 72 hours. Four of them were also maintained in supine
      posture for 72 hours as controls. The following immunological and neuroendocrine
      parameters have been analysed: peripheral white blood cells count, CD11b integrin
      expression and H(2)O(2) production by neutrophils, lymphocyte and monocyte
      phenotype, intracytoplasmic cytokine (IFN-gamma, TNF-alpha and IL-4) pattern,
      lymphocyte proliferation to mitogens and antigens, cortisol, ACTH,
      catecholamines, GH, LH, prolactin and testosterone plasma levels. RESULTS: In
      subjects maintained in antigravitary posture, norepinephrine, dopamine, cortisol,
      ACTH, GH and prolactin plasma levels increased whereas H(2)O(2) production by
      neutrophils, lymphocyte proliferation, NK cells number and intracytoplasmic IFN-g
      expression decreased. No significant modifications were observed in subjects
      maintained in supine posture. CONCLUSION: The results of this study indicate that
      several neuroendocrine and immunological parameters are modulated by a prolonged
      antigravitary posture on ground and may negatively affect astronauts defenses
      against pathogens during space flights.

PMID- 14976466
TI  - [Cytofluorimetric evaluation of peripheral blood dendritic cells in patients with
      Mediterranean Kaposi's sarcoma].
AB  - AIM: Kaposi's sarcoma (KS) is a lympho-angioproliferative disorder characterized
      by angiomatous nodules and plaques that mainly affect the skin. The disease is
      consistently associated with human herpesvirus-8 (HHV8) and with a state of
      preexistent immunosuppression. Dendritic cells (DCs) have an instrumental role in
      the activation and function of both innate and adaptative immune responses. At
      least 2 distinct subsets have been characterized in peripheral blood based on
      phenotypic markers: myeloid DCs (CD11c+), associated with Ag uptake, T cell
      activation and ability to secrete IL-12, and plasmacytoid DCs, high virus-induced
      IFN-alpha producing cells. Because of the role of both DC subtypes in antiviral
      and antitumor induced responses, we hypothesized that DCs could be involved in
      the onset and evolution of KS. METHODS: Thirty-five patients with mediterranean
      KS assigned to different clinical stages were compared with 51 healthy control
      subjects. Peripheral blood DCs were quantified and functionally characterised by
      flow cytometry directly on whole blood samples. The production of the regulatory
      cytokines, IL-12 and IL-10, was assessed as intracellular accumulation after
      incubation with or without lipopolysaccharide (LPS). RESULTS: Myeloid DCs
      identified as lineage-/HLA-DR+/CD11c+ cells were significantly lower in KS
      patients than in controls (0.54+/-0.25 vs 0.69 +/-0.26% of the peripheral blood
      mononuclear cells; p<0.017). Furthermore, CD11c+ DCs were lower in patients with
      more diffuse disease. Plasmacytoid DCs, identified as lineage-/HLA-DR+/CD123+
      cells, were lower in KS patients (0.23+/-0.19 vs 0.36+/-0.17; p<0.001). DCs from
      KS patients were more mature, as assessed by expression of the maturation marker
      CD83, and showed an impaired ability to produce IL-12 upon LPS stimulation, as
      compared with controls. CONCLUSION: The numerical and functional alterations of
      peripheral blood DCs observed in KS patients suggest an involvement of these
      cells in the onset and evolution of the disease.

PMID- 14976467
TI  - [Antidiabetic therapy in diabetic patients with coronary heart disease].
AB  - The role of metabolic control following acute myocardial infarction, (AMI) is
      still subject of study to date. The only study performed in diabetic patients
      with an AMI is the DIGAMI which demonstrated that endovenous insulin therapy in
      the acute phase, followed by multiple subcutaneous administrations of insulin
      therapy in the follow-up, was able to obtain not only a better metabolic control
      in both the acute phase and in the follow-up, but also a better survival only in
      the follow-up. Even if this latter fact is disappointing, endovenous insulin
      infusion seems to be the best approach to effectively contrast the metabolic
      events secondary to hyperglycemia which accompany AMI. From the DIGAMI study
      derives the indication of multiple insulin injections in diabetic patients having
      survived an AMI, even if doubt still exists as to whether it is the insulin
      therapy in itself or rather the metabolic compensation obtained that is
      responsible for a better survival rate. There is no controversy regarding the use
      of multiple (3 but above all 4/day) subcutaneous rapid insulin administrations at
      meal time and retard insulin administrations at bed time. Over the last few years
      ultrarapid insulin has become available as well the newcomer glargine, a retard
      insulin, which presents a homogeneous 24 hour release pattern. These insulin
      forms, obtained by genetic engineering, allow for a 4 daily dose administration,
      ultrarapid at meal times and glargine once daily, which mimic a more
      physiological insulin secretion and as such probably render them more
      efficacious. When oral drugs are opted for, it is imperative to have acquaintance
      with their half-lives, bonding properties with K(+)(ATP) channels, the
      antioxidant and antithromobophylic properties. It is necessary to modulate their
      use considering the glycemic daily rhythm in diabetics (glycemia tending to be
      high in the early morning and low in the evening). In order to obtain an optimal
      metabolic control it is essential to have the patient perform a glycemia level
      self-assessment by means of portable measuring instruments which employ
      instantaneous reactive strips. Self-assessment is imperative for the prevention
      of hypoglycemic episodes considered particularly dangerous in diabetic patients
      with coronary heart disease, even if studies which have demonstrated and
      documented this danger do not exist.

PMID- 14976468
TI  - Role of oral anti-diabetic agents in modifying cardiovascular risk factors.
AB  - Patients with type 2 diabetes have an increased risk for cardiovascular disease
      (CVD) and it accounts for up to 80% of excess deaths in these patients. It has
      been recognized that type 2 diabetes is associated with an increased prevalence
      of CVD risk factors, including hypertension, dyslipidemia, microalbuminuria, and
      altered hemostasis. The benefit of cardiovascular protection can only be
      partially explained by controlling hyperglycemia. Some of the oral agents used to
      treat hyperglycemia significantly modify other cardiovascular risk factors. This
      article will review oral agents used to treat type 2 diabetes and their effects
      on modifying CVD risk factors.

PMID- 14976469
TI  - Ketoacidosis and the hyperosmolar hyperglycemic state in adult diabetic patients.
      Diagnosis and treatment.
AB  - Diabetic ketoacidosis (DKA) and the hyperosmolar hyperglycemic state (HHS) are
      serious acute decompensations of type 1 and 2 diabetes mellitus due to various
      degrees of insulin deficiency and increased levels of counterregulatory hormones.
      They are characterized by hyperglycemia and hyperosmolarity in HHS, and by
      hyperglycemia and ketoacidosis in DKA with major electrolyte imbalance; both can
      co-exist. Precipitating factors can usually be identified. The diagnosis can
      usually be suspected on clinical grounds, but must be confirmed by laboratory
      investigation. Treatment consists of appropriate rehydration, intravenous insulin
      therapy and potassium supplementation. Careful monitoring of the patient's
      clinical and biochemical status throughout treatment is critical. Excess
      mortality still occurs, particularly for HHS, emphasizing the importance of
      patient education and regular follow-up to prevent these potentially fatal
      complications.

PMID- 14976470
TI  - Diabetic retinopathy.
AB  - Blindness is one of the most feared complications of diabetes but also one of the
      most preventable. Diabetic retinopathy (DR) in the way of proliferative
      retinopathy (PDR) and macular oedema (ME) is the commonest cause of new cases of
      legal blindness in Europe as in North America in the age group 30 to 70-74 years.
      DR is due to microangiopathy affecting the retinal precapillary arterioles,
      capillaries, and venules. Detection of the earliest signs of DR is an essential
      requirement of diabetics care leading to early preventive and treatment
      strategies which can arrest progression of this serious consequence of diabetes.
      Glycemic control and stricter control of hypertension have a clear effect on the
      development of the microvascular complications of diabetes like DR, while
      treatment options of severe non proliferative and proliferative forms of DR are
      limited to laser photocoagulation and vitrectomy. Photocoagulation has proven
      efficacy in slowing down the progression of DR and vitrectomy can prevent vision
      loss in case of advanced DR. Older and newer pathogenesis-based approaches to
      medical treatment are currently under evaluation by randomized controlled
      clinical studies still with inconclusive RESULTS: A review of these studies is
      proposed.

PMID- 14976471
TI  - Abrupt occurrence of high fever and rash in a patient treated with sulphasalazine
      for psoriatic arthritis.
AB  - We report a singular clinical condition observed following a short duration
      treatment with sulphasalazine (SSZ) in a 64-year-old woman affected by psoriatic
      arthritis. Two weeks after starting treatment, a high degree, subcontinuous fever
      occurred, together with systemic discomfort, fatigue, headache, and ultimately a
      moderate wakefulness impairment. Upon admission to the hospital, a malar rash
      became evident. Modest notes of hepatotoxicity were also evident. All of the
      symptoms suddenly resolved after SSZ withdrawal. The markers of hepatitis become
      negative just 2 months later. It is interesting to note that after dismissal, in
      order to counteract the severe arthritic conditions and the presence of a type 2
      diabetes, a combined therapy with methotrexate and cyclosporin had to be used,
      with no renal or hepatic side effects and remarkable therapeutic effects. No
      markers of autoimmunity were found in this patient. The chronology and the
      clinical events here described may confirm the hypothesis of a idiosyncratic
      reaction to SSZ, closely resembling a rare, sometimes irreversible, condition
      known as "the 3 week sulphasalazine syndrome".

PMID- 14976472
TI  - Use of proteomic patterns to screen for gastrointestinal malignancies.

PMID- 14976473
TI  - Thorough intraoperative analysis of breast sentinel lymph node biopsies:
      histologic and immunohistochemical findings.
AB  - BACKGROUND: We report the use of a thorough intraoperative sentinel lymph node
      (SLN) biopsy screening procedure for patients with small N0 breast tumors.
      METHODS: Sixty-eight consecutive female patients with monofocal stage I or
      "small" stage II (ie, 2.1-3.0 cm) N0 tumors received intraoperative SLN screening
      according to a procedure on the basis of comprehensive histologic analysis and
      cytokeratin immunohistochemical determination (CkID) of adjacent frozen sections
      of the SLN taken at 50-microm cutting levels. RESULTS: The maximum duration of
      intraoperative analysis including CkID was 40 minutes. Positive SLN were found in
      15/68 (22%) patients (always in a single node); they included 5 instances of
      micrometastasis and 3 of carcinomatous lymphangitis. In the 14 patients who
      underwent axillary lymph node dissection, no further metastasis was found at
      histologic analysis or CkID. SLN positivity correlated with histologic type
      (P=.044), intratumoral or peritumoral vascular invasion (P<.001) and Mib1 score
      (P=.042). CONCLUSIONS: It is possible for an experienced team to perform
      intraoperative SLN screening for T1 or small T2 N0 breast tumors with frozen
      sections taken at 50-microm cutting levels. This procedure facilitates
      identification of micrometastasis, as well as of carcinomatous lymphangitis to
      help understand the biologic implications of these small lesions in the long
      term. SLN positivity appears to correlate with histologic type,
      intratumoral/peritumoral vascular invasion and Mib1 score.

PMID- 14976475
TI  - Sentinel lymph node biopsy using computed tomography-lymphography in patients
      with breast cancer.
AB  - BACKGROUND: The sentinel lymph node biopsy (SLNB) technique is established in the
      treatment of breast cancer. The current technique of mapping the SLN with blue
      dye or radiotracers requires a learning period. Tracer and injection site
      selection and intraoperative pathologic examination have been discussed. METHODS:
      We developed a three-dimensional computed tomography lymphography (3D CT-LG)
      technique with commercially available iopamidol. SLNB and backup dissection were
      performed in 40 patients with T1 and T2 breast cancer. Feasibility and efficacy
      of CT-LG were examined. RESULTS: In all patients, lymph flow and the surrounding
      anatomical environment were visualized with 3D CT-LG. SLNB was successful because
      of accurate navigation by 3D CT-LG. SLN was detected in all patients, whereas dye
      navigation failed in seven fatty axilla and two patients with prior excisional
      biopsy. Backup dissection confirmed the accuracy of CT-LG-guided SLNB. A false
      negative result was found in only one patient. Preoperative prediction was
      feasible in cases of SLN metastasis. CONCLUSIONS: CT-LG allowed accurate SLN
      localization by quickly and adequately visualizing the direct connection between
      the SLN and its afferent lymphatic vessels. Detailed cross-sectional images of
      lymphatic anatomy during CT resulted in successful SLNB with shortening of the
      presurgical examination schedule.

PMID- 14976476
TI  - Perinodal involvement of cancer cells in gastric cancer patients.
AB  - BACKGROUND: En-bloc resection for cancer has been a standard procedure based on
      the concept that there may be a small number of "invisible" cancer cells around
      the primary tumor and metastatic lymph nodes. However, there are few
      histopathologic studies of this issue. METHODS: Perinodal involvement of cancer
      cells, defined as existence of cancer cells in the attached fatty tissue around
      the dissected lymph nodes, was assessed in 123 node-positive and 15 node-negative
      gastric cancers by both hematoxylin-eosin staining and immunohistochemistry.
      RESULTS: Perinodal involvement was found in 79 (57%) of the 138 patients. The
      incidence was higher in patients with tumors invading the deeper layer, the
      macroscopic diffuse type, the presence of lymphatic or vascular invasion (P<.05),
      and advanced disease (stage I, 17%; II, 62%; III, 67%; IV, 80%). Survival of
      patients with perinodal involvement was less than that of patients without
      perinodal involvement (46% vs 87%; P<.005). Perinodal involvement was found, by
      multivariate analyses, to be a significant prognostic factor. CONCLUSIONS:
      Perinodal cancer cells are observed frequently in gastric cancers with lymph node
      metastases, and the involvement appears to be a reliable prognostic factor for
      gastric cancers.

PMID- 14976477
TI  - Selective use of diagnostic laparoscopy prior to planned hepatectomy for patients
      with hepatocellular carcinoma.
AB  - BACKGROUND: Patients with hepatocellular carcinoma (HCC) are frequently found to
      be inoperable at surgical exploration. Laparoscopy may reduce the rate of
      unnecessary laparotomy in these patients. However, there are no criteria for
      selective use of laparoscopy. METHODS: Sixty patients with potentially operable
      HCC underwent laparoscopy prior to planned partial hepatectomy. Intraoperative
      findings and postoperative course were analyzed, and factors for the selective
      use of laparoscopy were identified. RESULTS: Fourteen of 19 inoperable patients
      (74%) were identified by means of laparoscopy, which increased the resectability
      rate from 68% to 89%. Compared with patients undergoing exploratory laparotomy
      only, patients determined to be inoperable on laparoscopy had significantly less
      intraoperative blood loss, a shorter operating room time, and a briefer hospital
      stay. In a multivariate analysis, clinically apparent liver cirrhosis and
      radiologic evidence of major vascular invasion or bilobar tumors predicted the
      likelihood of finding inoperable disease at laparoscopy. The initial use of
      laparoscopy avoided unnecessary laparotomy in almost 30% of patients with-but
      only 5% of patients without-these features. CONCLUSIONS: If high-risk patients
      with HCC are selectively targeted, the yield of laparoscopy is increased and
      unnecessary laparotomy may be avoided. In patients without cirrhosis, major
      vascular invasion, or bilobar tumors, the yield of laparoscopy is low and is
      therefore not generally recommended.

PMID- 14976478
TI  - Using a risk score for conversion from laparoscopic to open cholecystectomy in
      resident training.
AB  - BACKGROUND: We previously developed a risk score for conversion from laparoscopic
      to open cholecystectomy (RSCLO). The aim of this study is to validate this
      scoring system in a new patient population and test its use in case selection for
      resident training. METHODS: The data of 1,000 laparoscopic cholecystectomies (LC)
      that had been performed in our clinic between 1992 and 1999 were analyzed
      retrospectively, and RSCLO was developed. Scores take values between -20 and 41;
      values below -3 represent low risk, and values over -3 represent high risk.
      Analyses in this group of patients showed that at least 15 cases have to be
      performed for adequate LC training. The current study is a clinical prospective
      study based on data of the previous study and evaluates RSCLO in a new patient
      population of 400 LCs. All patients were scored preoperatively; surgeons who had
      performed 15 or fewer LCs previously operated only patients with a score below 
      3. Patients with high scores (>values of -3) were operated only by surgeons who
      had performed at least 16 LCs. Results of the first 1,000 cases and later 400
      cases (new patient population of the current study) were compared in terms of
      conversion to open cholecystectomy, complications, and operation times. RESULTS:
      Both in the first 1,000 patients and later in 400 patients, increasing scores
      resulted with higher conversion rates and complication rates and longer operation
      times (P<.05). In the later 400 patients, conversion rate (4.8% vs 3.0%, P=.08),
      complication rate (5.5% vs 3.5%, P=.07), and mean operation time (56.8 min vs
      52.5 min, P=.004) were decreased when compared with the first 1,000 patients. In
      resident training cases, conversion and complication rates decreased to 0%, and
      mean operation time was shortened by nearly 10 minutes. In high-score difficult
      cases, conversion and complication rates decreased, and mean operation time was
      shortened by nearly 20 minutes. CONCLUSIONS: This risk score can predict the
      difficulty of LC cases reliably. Scoring patients preoperatively can decrease the
      problems in training cases, and management of difficult cases may be left to
      experienced surgeons.

PMID- 14976479
TI  - Socioeconomic characteristics of the population eligible for obesity surgery.
AB  - BACKGROUND: Obesity is increasing in the American population in epidemic
      proportions. Weight reduction surgery results in sustained weight loss for
      morbidly obese individuals-a group of patients refractory to nonsurgical obesity
      treatment. Surgical indications were outlined in a National Institutes of Health
      (NIH) consensus conference published in 1991. Using the NIH criteria, we compared
      the socioeconomic characteristics of the population eligible for these operations
      to those receiving them. METHODS: The 2000 National Health Interview Survey
      database was examined to identify how many individuals in the American population
      were eligible for obesity operations. Socioeconomic characteristics for those
      individuals were then assessed. The Healthcare Cost and Utility Project and
      National Hospital Discharge Survey databases were queried to determine how many
      gastric bypass operations were performed and what the patient's socioeconomic
      characteristics were. RESULTS: There are 5,324,123 people, or 2.8% of the
      American population, who are eligible for obesity surgery. Of these, a
      disproportionate number were black, poorly educated, or impoverished, and 38%
      rely on Medicare or Medicaid for their health insurance. Of the 28,590 gastric
      bypass operations performed in 2000, only 13% of patients used Medicare or
      Medicaid to pay for the operation. Fewer than expected operations were performed
      on blacks. Regional differences were observed with disproportionately more
      operations performed in the Northeast and fewer in the Midwest than would be
      predicted from the surgery-eligible population living in these regions.
      CONCLUSIONS: A significant fraction of the American population could potentially
      benefit from obesity surgery. However, many of those individuals are black,
      poorly educated, and impoverished. Public assistance programs need to account for
      these patients. Centers performing bariatric operations need to accommodate the
      educational and financial constraints these patients have when planning long-term
      postoperative care.

PMID- 14976480
TI  - Expression of pancreatic duodenal hoemobox-1 in pancreatic islet neogenesis after
      surgical wrapping in rats.
AB  - BACKGROUND: Surgical wrapping (SW) of the pancreas causes islet neogenesis in
      rodents. Pancreatic duodenal hoemobox-1 (PDX-1) is one of the transcriptional
      factors needed by pancreatic stem cells to develop a mature pancreas. The purpose
      of this study was to determine whether islet neogenesis arises from ductal cells
      and whether PDX-1 is involved in this process. METHODS: SW consisted of
      nonocclusive wrapping of the pancreas in rats. The wrapped pancreas was then
      harvested, insulin content was measured, and immunohistochemical analysis for
      insulin, cytokeratin, and PDX-1 was performed. RESULTS: The endocrine area of the
      wrapped pancreas significantly increased after SW. Double immunostaining
      identified cells positive for both insulin and cytokeratin in or along the
      epithelial cell lining of the ductal structures and in the centroacinar cells.
      PDX-1-positive cells were detected in both control islets and islets examined
      after SW, but these cells were observed in the exocrine area only after SW.
      Double staining also showed that cells positive for PDX-1 but negative for
      insulin were present in the exocrine area 1 day after SW and that cells positive
      for both PDX-1 and insulin had developed 3 days after SW. CONCLUSIONS: In the
      process of adult islet neogenesis after SW, cells in the acini and ductal
      structures developed into PDX-1-expressing cells, supposedly progenitor cells,
      which in turn became insulin-producing cells and thus might be the origin of
      small islets.

PMID- 14976481
TI  - Reduction in postoperative adhesion formation and re-formation after an abdominal
      operation with the use of N, O - carboxymethyl chitosan.
AB  - BACKGROUND: Postoperative adhesions have proven to be intractable complications
      after abdominal operations. This study assessed the efficacy of N, O -
      carboxymethyl chitosan (NOCC) to limit adhesion formation and re-formation in a
      rabbit abdominal surgery model. METHODS: In study 1 (adhesion formation),
      injuries to the large bowel, cecum, and abdominal sidewall were generated in
      rabbits. The rabbits (10/group) were randomly assigned to 1 of 5 treatment
      groups: Group A received no NOCC treatment; in group B, NOCC gel was applied
      directly to the injured site and NOCC solution was applied throughout the
      abdominal cavity; in group C, NOCC gel was applied near the injured site and NOCC
      solution was applied as above; in group D, NOCC gel was applied distant to the
      injury and NOCC solution was applied as above; in group E, a mixture of NOCC gel
      and solution was applied at the injured site. Adhesions were evaluated 14 days
      later. In study 2 (adhesion re-formation), adhesions were generated as above but
      were then lysed by careful dissection. After adhesiolysis, the rabbits (9/group)
      were treated with NOCC gel and solution at the site of adhesiolysis or left
      untreated. Adhesion re-formation was assessed 14 days later. In study 3
      (mechanism of action), sterile tissue culture plates were coated with NOCC and
      adhesion of cultured, radiolabeled murine fibroblasts to the plates was assessed.
      RESULTS: In study 1, animals treated with NOCC gel and solution showed reduced
      adhesion formation (P<.01). NOCC gel was equally efficacious if applied on the
      site of injury or near the site of injury but less efficacious if applied at a
      site distant to the injury. In study 2, animals treated with NOCC gel and
      solution showed less adhesion re-formation compared with the untreated control
      animals (P<.01). In study 3, murine fibroblasts did not adhere to NOCC-coated
      tissue culture plates. CONCLUSIONS: NOCC gel and solution can reduce adhesion
      formation and re-formation in this rabbit model. The inability of fibroblasts to
      adhere to NOCC solution-coated surfaces suggests that NOCC may act as a
      biophysical barrier.

PMID- 14976482
TI  - B cell response to tumor antigens is associated with depletion of B progenitors
      in murine colocarcinoma.
AB  - BACKGROUND: B cells that produce antibodies to autologous tumor antigens have
      been found in patients with colon cancer; the significance of this phenomenon
      remains unknown. Normally, the elimination of autoreactive B cells occurs in the
      bone marrow during their maturation. We studied the production of antibodies to
      syngeneic tumor antigens and the maturation of bone marrow B cells in
      experimental colocarcinoma model. METHODS: BALB/c mice and syngeneic CT26 colon
      cancer cell line were used. Reactivity of serum antibodies was tested in Western
      blot analysis and flow cytometry against CT26 antigens. The number of bone marrow
      B lineage cells was evaluated with specific antibodies and flow cytometry
      analysis. RESULTS: A significant decrease in the number of B cell precursors
      occurred in tumor-bearing mice; it normalized 3 weeks after the removal of CT26
      tumors. The number of mature B cells was normal. Serum antibodies from tumor
      bearing mice recognized intracellular and not surface antigens of CT26 cells.
      CONCLUSION: Experimental colon cancer induces B cell response to intracellular,
      but not surface, tumor cell antigens and restricts the B cell repertoire by
      depleting their precursors.

PMID- 14976483
TI  - Transphrenic approach to subphrenic abscesses.

PMID- 14976484
TI  - Posterior perforation of peptic ulcers: presentation and outcome of an uncommon
      surgical emergency.
AB  - BACKGROUND: Posterior perforation of peptic ulcer is a distinct clinical entity
      not commonly encountered. This report evaluates the presentation, diagnosis,
      management, and outcome of this acute surgical condition. METHODS: We reviewed
      records of 9 patients with posterior perforations who were treated at our
      institution from January 1990 to June 2002. RESULTS: This condition was
      characterized by insidious onset of upper abdominal pain and delayed
      presentation. Abdominal examinations were equivocal in 7 patients on admission.
      Pneumoperitoneum on chest roentgenogram, when present, was a crucial diagnostic
      indicator of intra-abdominal pathology. The diagnosis was made intraoperatively
      in all cases; findings were sealed perforation, localized retroperitoneal
      abscess, or generalized contamination of the lesser sac and peritoneal cavity.
      Observed adverse operative risk factors included prolonged perforation (>24
      hours), pre-existing chronic medical illnesses, and preoperative hypotension. In
      addition, significant peritoneal contamination at celiotomy, major resection
      (gastrectomy), and gastric perforations were noted to be associated with a poor
      outcome: 4 of the 9 patients died. CONCLUSION: A high index of suspicion is
      important. When a retroperitoneal collection is noted at celiotomy, posterior
      perforation of peptic ulcer should be actively excluded.

PMID- 14976485
TI  - Laparoscopic adjustable gastric banding in the treatment of obesity: a systematic
      literature review.
AB  - BACKGROUND: We attempted to compare the safety and efficacy of laparoscopic
      adjustable gastric banding with vertical-banded gastroplasty and gastric bypass.
      Morbid obesity presents a serious health issue for Western countries, with a
      rising incidence and a strong association with increased mortality and serious
      comorbidities, such as diabetes, hyperlipidemia, and cardiovascular disease.
      Unfortunately, conservative treatment options have proven ineffective. Surgical
      interventions, such as vertical-banded gastroplasty (stomach stapling), Roux-en-Y
      gastric bypass, and, more recently, laparoscopic gastric banding have been
      developed with the aim of providing a laparoscopically placed device that is safe
      and effective in generating substantial weight loss. METHODS: Electronic
      databases were systematically searched for references relating to obesity surgery
      by (1) laparoscopic adjustable gastric banding (LAGB), (2) vertical banded
      gastroplasty (VBG), and (3) Roux-en-Y gastric bypass (RYGB). RESULTS: Only 6
      studies reported comparative results for laparoscopic gastric banding and other
      surgical procedures. One study reported comparative results for all 3 surgical
      procedures, and this study was only of moderate quality. In total, 64 studies
      were found that reported results for LAGB and 57 studies reported results on the
      comparative procedures. LAGB was associated with a mean short-term mortality rate
      of approximately 0.05% and an overall median morbidity rate of approximately
      11.3%, compared with 0.50% and 23.6% for RYGB, and 0.31% and 25.7% for VBG.
      Overall, all 3 procedures produced considerable weight loss in patients up to 4
      years in the case of LAGB (the maximum follow-up available at the time of the
      review), and more than 10 years in the case of the comparator procedures.
      CONCLUSIONS: The Australian Safety and Efficacy Register of New Interventional
      Procedures-Surgical Review Group concluded that the evidence base was of average
      quality up to 4 years for LAGB. Laparoscopic gastric banding is safer than VBG
      and RYGB, in terms of short-term mortality rates. LAGB is effective, at least up
      to 4 years, as are the comparator procedures. Up to 2 years, LAGB results in less
      weight loss than RYGB; from 2 to 4 years there is no significant difference
      between LAGB and RYGB, but the quality of data is only moderate. The long-term
      efficacy of LAGB remains unproven, and evaluation by randomized controlled trials
      is recommended to define its merits relative to the comparator procedures.

PMID- 14976486
TI  - Synchronous colon and pancreatic cancers in a patient with Peutz-Jeghers
      syndrome: report of a case and review of the literature.

PMID- 14976487
TI  - Combined intrahepatic and extrahepatic biliary tree abnormality in the era of
      laparoscopic cholecystectomy.

PMID- 14976498
TI  - Meaning of bereavement among older African American widows.
AB  - In spite of the increase in research on spousal bereavement, researchers have not
      specifically addressed the impact that ethnicity may have on the bereavement
      experience. The results of this descriptive phenomenological study increase the
      understanding of spousal bereavement among older African American widows.
      Storytelling was at the heart of every participant's description of her
      bereavement experience. Six themes were identified: awareness of death, care
      giving, getting through, moving on, changing feelings, and financial security.
      For nurses to effectively intervene in the lives of bereaved older African
      American widows, they must consider each widow's culture, heritage, and lived
      experiences, which can be ascertained through eliciting and listening to the
      widow's life stories.

PMID- 14976499
TI  - Nursing older people in Thailand: Embryonic holistic rhetoric and the biomedical
      reality of practice.
AB  - Qualitative research, informed by grounded theory, was used to investigate
      gerontic nursing practices in Bangkok, Thailand. In-depth interviews with older
      persons, their families, and nurses were conducted and the data were analyzed
      using constant comparison. Five inter-related major themes in gerontic nursing
      practice were revealed: the reality of nursing practice, family caregiving, views
      of gerontic nursing, tension, and communication. It was concluded that, though
      nursing rhetoric supported holistic care, the reality of everyday practice is
      still biomedical in focus.

PMID- 14976500
TI  - Early detection of type 2 diabetes among older African Americans.
AB  - The purpose of this research was to determine whether a group of African
      Americans who had no diagnosis of type 2 diabetes had elevated blood glucose
      levels and other risk factors indicative of type 2 diabetes. A convenience sample
      of 20 African American adults 50 years and older participated in the pilot study.
      Participants were screened for elevated fasting capillary blood glucose levels
      and related risk factors such as hypertension, high cholesterol levels, and high
      body mass index. Frequency data indicated that at least 50% of participants had
      capillary glucose levels greater than 110 mg/dL. An overwhelming majority of the
      participants with elevated glucose levels had one or more other risk factors for
      type 2 diabetes. Evidence-based practice clearly indicates that an early
      detection and control of type 2 diabetes can prevent complications and also help
      prevent coronary artery disease.

PMID- 14976501
TI  - Complementary and alternative therapy use by older adults in three ethnically
      diverse populations: a pilot study.
AB  - Americans have overwhelmingly embraced complementary and alternative therapies.
      Although the primary purpose of this study was to refine a questionnaire on
      complementary and alternative therapy use by older adults, the findings of this
      pilot study identified knowledge and use of complementary and alternative
      therapies in a convenience sample of 60 older adults, 54 to 92 years of age from
      three ethnically diverse senior centers. Eighty percent of the participants used
      two or more therapies. There were no significant differences in therapy use by
      ethnicity. The most commonly used therapies were prayer, vitamins, diet, massage,
      and meditation. The participants rated the effectiveness of therapies higher than
      their knowledge of the therapies. Older adults need accurate information from
      health care providers to make safe decisions regarding the combination of
      complementary therapies and prescribed treatments to reduce the risk of
      interaction.

PMID- 14976502
TI  - Oral history: Validating contributions of elders.
AB  - Recording memories of World War II is an intervention that can humanize geriatric
      care in addition to the historical significance provided. Participants in this
      oral history project described memories of World War II and expressed themes of
      patriotism, loss, tense moments, makeshift living, self-sufficiency, and
      uncertain journey. Their ethnic roots were primarily Scandinavian, Dutch, German,
      and English. The nursing home participants were slightly older than the community
      participants (mean ages: 85.5 and 82.4 years, respectively). More women (58%)
      than men (42%) participated, and 35% of the participants were veterans (eight men
      one woman). Nursing home and community residents participated in this project,
      and reciprocal benefits were experienced by participants and listeners alike.
      Memories of World War II provide a meaningful topic for oral histories. Listening
      and valuing oral history supports, involves, and validates elders. Oral history
      has reciprocal benefits that can create a culture to enhance a therapeutic
      environment.

PMID- 14976503
TI  - Anticipatory grief and chronicity: Elders and families in racial/ethnic minority
      groups.
AB  - This article provides some brief demographic data on aging, describes
      anticipatory grief, and presents two cases of anticipatory grief involving elders
      in racial/ethnic minority groups with some analysis including cultural values and
      beliefs and some practical guidelines.Melen McBride and Mycel JacobIrene Daniels
      and Lillian DavisIrene and Don Lewis The discussion ends with a useful process
      model for improving communications with elders in racial/ethnic groups and their
      families.

PMID- 14976504
TI  - Dolores Marsh Alford, PhD, RN, FAAN--leader and innovator.

PMID- 14976510
TI  - Update on dementia medications for 2004.

PMID- 14976511
TI  - Research guiding practice related to cultural issues at end of life care.

PMID- 14976513
TI  - Research review: hypertension management in African Americans.

PMID- 14976514
TI  - NCGNP legislative update: a review of the nursing shortage legislation.

PMID- 14976517
TI  - MAPK cascade signalling and synaptic plasticity.

PMID- 14976518
TI  - Anterior prefrontal cortex: insights into function from anatomy and neuroimaging.

PMID- 14976519
TI  - Glycans and neural cell interactions.
AB  - Carbohydrate-carrying molecules in the nervous system have important roles during
      development, regeneration and synaptic plasticity. Carbohydrates mediate
      interactions between recognition molecules, thereby contributing to the formation
      of a complex molecular meshwork at the cell surface and in the extracellular
      matrix. The tremendous structural diversity of glycan chains allows for immense
      combinatorial possibilities that might underlie the fine-tuning of cell-cell and
      cell-matrix interactions.

PMID- 14976520
TI  - Molecular mechanisms of taste-recognition memory.

PMID- 14976521
TI  - Look away: the anti-saccade task and the voluntary control of eye movement.

PMID- 14976522
TI  - The role of fixational eye movements in visual perception.

PMID- 14976523
TI  - A century of cerebellar somatotopy: a debated representation.

PMID- 14976524
TI  - Loss of FHIT protein expression is related to high proliferation, low apoptosis
      and worse prognosis in non-small-cell lung cancer.
AB  - The fragile histidine triad (FHIT) gene, located at chromosome 3p14.2, is deleted
      in many solid tumors, including lung cancer. Its protein product is presumed to
      have tumor suppressor function. We investigated the incidence of loss of
      heterozygosity and loss of FHIT expression in a series of non-small-cell lung
      carcinomas and its correlation to apoptosis, proliferation index and prognosis.
      FHIT expression was determined by immunohistochemistry in formalin-fixed paraffin
      embedded tissues from 54 squamous cell carcinomas (SCC) and 44 adenocarcinomas
      (AC) of the lung. DNA from frozen tumor and corresponding normal tissues were
      analyzed for allelic losses at two loci located internal (D3S1300, D3S1234) and
      three loci in flanking regions centromeric and telomeric (D3S1210, D3S1312,
      D3S1313) to the FHIT gene. Apoptosis was detected by terminal
      deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL).
      Proliferation index was determined with ki-67 and flow cytometric analysis. We
      correlated the results with tumor histology, prognosis and some
      immunohistochemical markers (p53, bcl-2, bax, c-myc, p21(waf1), cyclin-D1). FHIT
      expression was related to tumor histology: 52 of 54 (96.3%) SCC and 20 of 44
      (45.5%) AC were negative for FHIT (P<0.0001). We found LOH at 3p14.2 in 67.8% of
      the 98 cases: 72.3% of SCC and 61.4% of AC. Loss of FHIT expression was
      associated with a higher proliferation index (ki-67, P=0.007; flow cytometry,
      P<0.004) and lower apoptotic index (P=0.018). LOH at FHIT gene were associated to
      a high proliferation (flow cytometry, P<0.001) and lower apoptotic level
      (P=0.043). The log-rank test demonstrated a significant inverse correlation
      (P=0.039) between loss of FHIT expression and patient survival. FHIT plays an
      important role in the development of non-small-cell lung cancer, particularly in
      SCC. Loss of FHIT protein is correlated with a high proliferation and low
      apoptotic index in tumor cells, and is an independent prognostic indicator for
      the clinical outcome in patients with these tumors.

PMID- 14976525
TI  - Post-transplant plasma cell myeloma and polymorphic lymphoproliferative disorder
      with monoclonal serum protein occurring in solid organ transplant recipients.
AB  - Post-transplant lymphoproliferative disorders are mostly Epstein-Barr virus
      related, B-cell tumors that develop as a consequence of immunosuppressive therapy
      in recipients of solid organ or bone marrow transplants. These disorders range
      from reactive, polyclonal plasmacytic hyperplasia to those that are
      morphologically and genotypically indistinguishable from typical non-Hodgkin's
      lymphomas. Plasma cell myeloma occurring after solid organ transplantation is
      rare. We report three plasma cell myeloma post-transplant lymphoproliferative
      disorder cases and one polymorphic, monoclonal post-transplant
      lymphoproliferative disorder case associated with a monoclonal serum protein. All
      three plasma cell myeloma post-transplant lymphoproliferative disorder cases had
      clinical, radiologic, and pathologic features of conventional plasma cell
      myeloma. The one polymorphic post-transplant lymphoproliferative disorder case
      was associated with an IgM monoclonal serum protein and was morphologically
      indistinguishable from a lymphoplasmacytic lymphoma. Three of the four cases,
      including the one polymorphic post-transplant lymphoproliferative disorder case,
      were positive for Epstein-Barr virus encoded small RNA by in situ hybridization.
      One patient died of plasma cell myeloma post-transplant lymphoproliferative
      disorder. The remaining three patients are alive: two are completely free of post
      transplant lymphoproliferative disorder, and one has shown partial response to
      therapy. We compare the clinicopathologic features of these cases with those in
      the literature.

PMID- 14976526
TI  - Diagnostic importance of CD179a/b as markers of precursor B-cell lymphoblastic
      lymphoma.
AB  - Surrogate light chains consisting of VpreB (CD179a) and lambda5 (CD179b) are
      expressed in precursor B cells lacking a complete form of immunoglobulin and are
      thought to act as substitutes for conventional light chains. Upon differentiation
      to immature and mature B cells, CD179a/b disappear and are replaced with
      conventional light chains. Thus, these molecules may be useful as essential
      markers of precursor B cells. To examine the expression of the surrogate light
      chain components CD179a and CD179b in precursor B-cell lymphoblastic lymphoma, we
      analyzed tissue sections using immunohistochemistry techniques. Among a number of
      monoclonal antibodies for the surrogate light chains, VpreB8 and SL11 were found
      to detect CD179a and CD179b, respectively, in acetone-fixed fresh frozen
      sections. Moreover, we also observed VpreB8 staining in formalin-fixed, paraffin
      embedded sections. Using these antibodies, we found that CD179a/b were
      specifically expressed in precursor B-cell lymphoblastic lymphomas, but not in
      mature B-cell lymphomas in childhood. Furthermore, other pediatric tumors that
      must be included in a differential diagnosis of precursor B-cell lymphoblastic
      lymphoma, including precursor T-cell lymphoblastic lymphoma, extramedullary
      myeloid tumors, and Ewing sarcoma, were also negative for both CD179a and CD179b.
      Our data indicate that CD179a and CD179b may be important markers for the
      immunophenotypic diagnosis of precursor B-cell lymphoblastic lymphomas.

PMID- 14976528
TI  - WITHDRAWN:Epidemiology of prostate cancer and its precursors.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 14976527
TI  - Characteristic peripheral blood findings in human ehrlichiosis.
AB  - Human ehrlichiosis is a potentially fatal tick-borne illness if not treated
      promptly. Ehrlichia infection is difficult to diagnose as the organism does not
      grow in standard blood culture medium and serological confirmation of infection
      takes several days to weeks. The most timely way of confirming Ehrlichia
      infection is identification of characteristic cytoplasmic morulae in peripheral
      blood leukocytes. A total of 23 patients with clinical and laboratory findings
      suggesting a rickettsial infection were tested for Ehrlichia using polymerase
      chain reaction and culture: 16 cases contained Ehrlichia DNA by polymerase chain
      reaction (15 E. chaffeensis, one E. ewingii), including 14 cases in which the
      blood culture grew Ehrlichia. The cases that contained Ehrlichia DNA by
      polymerase chain reaction had lower mean white blood cell and platelet counts and
      more numerous atypical lymphocytes and pronounced toxic change than cases in
      which Ehrlichia DNA was not detected. Cytoplasmic morulae were identified on
      peripheral blood smears in six (five E. chaffeensis, one E. ewingii) of 16 (38%)
      of the cases that contained Ehrlichia DNA, including 4/4 (100%) immunocompromised
      and 2/12 (17%) immunocompetent patients. Morulae were present in monocytes in E.
      chaffeensis-infected cases and granulocytes in the E. ewingii-infected case. In
      two immunocompromised patients, the number of infected cells was 1-10%, but in
      four patients it was <0.2%. In conclusion, peripheral blood film examination is
      diagnostic in a substantial number of Ehrlichia infections, particularly in
      immunocompromised patients. The number of infected white blood cells may be less
      than 0.2%, requiring examination of more than 500 white blood cells. Associated
      changes prompting careful film review include prominent toxic granulation and
      atypical large granular lymphocytes.

PMID- 14976529
TI  - Promoter hypermethylation and protein expression of the p16 gene: analysis of 43
      cases of B-cell primary gastric lymphomas from China.
AB  - The p16 (CDKN2a/INK4a) gene is an important tumor-suppressor gene, involved in
      the p16/cyclin-dependent kinase/retinoblastoma gene pathway of cell cycle
      control. The p16 protein is considered to be a negative regulator of the pathway.
      Promoter hypermethylation resulting in inactivation of the p16 gene has been
      found in various hematopoietic malignancies, including non-Hodgkin's lymphoma,
      and may play a role in transformation/clinical aggressiveness of those tumors.
      However, the p16 protein expression in primary gastric lymphoma has not been
      studied. In this study, we characterize protein expression and promoter
      hypermethylation of the p16 gene in B-cell primary gastric lymphomas from China.
      In all, 43 cases of B-cell primary gastric lymphoma were investigated. They
      consisted of 24 (56%) cases of diffuse large-cell lymphoma, 12 (28%) cases of
      extranodal marginal zone lymphoma, six (14%) cases of extranodal marginal zone
      lymphoma with large-cell transformation and one (2%) case of follicular lymphoma.
      Loss of p16 protein expression was found in 34 (79%) out of 43 cases, while the
      remaining nine (21%) cases showed positivities for the p16 protein. All 43 cases
      were further characterized by methylation-specific polymerase chain reaction
      (PCR) to analyze p16 promoter hypermethylation status. In total, 11 (26%) of 43
      cases were positive for p16 promoter hypermethylation. Among those, 10 (30%) out
      of the 33 cases negative for the p16 immunostaining showed promoter
      hypermethylation, whereas only one (10%) out of the 10 cases that were positive
      for the p16 immunostaining displayed promoter hypermethylation. Of the 43 cases,
      30 had limited pathologic data at the time of resection. Primary gastric lymphoma
      involved extragastric sites (lymph node or liver) in 17 (57%) of 30 cases, while
      the remaining 13 (43%) cases were only limited to the stomach. Loss of p16
      protein expression was found in 14 (82%) of 17 cases with extragastric
      involvement and in 11 (85%) of 13 cases without such involvement. In conclusion,
      loss of p16 protein expression is frequent in those B-cell primary gastric
      lymphomas and approximately one-third of such loss correlated with promoter
      hypermethylation. Despite limited pathologic data, loss of p16 protein expression
      appears not to be correlated with extragastric involvements.

PMID- 14976530
TI  - Efficacy of manual dissection of lymph nodes in colon cancer resections.
AB  - The adequacy of lymph node dissection of colonic resection specimens influences
      the clinical and pathologic staging, leading to important postsurgical treatment
      decisions. Although manual lymph node dissection is the current standard at most
      institutions, recent statistical studies indicate that all lymph nodes, including
      those measuring 1-2 mm, should be recovered to be assured of lymph node negative
      status. Thus, we tested the efficacy of gross dissection by submitting the entire
      residual mesenteric fat. We analyzed 15 randomly chosen colonic resections (2
      pT1, 1 pT2, 11 pT3, 1 pT4). After standard gross dissection of lymph nodes and
      submission of colonic material for diagnosis, the entire remaining mesenteric
      material was dehydrated over several days by serial washing in alcohol and
      acetone. All of the mesenteric tissue was submitted for histology. The average
      number of nodes found by original gross inspection was 20.8, while the average
      number of additional nodes found after clearing was 68.6. In all, 83% of the
      additional nodes were 2.0 mm or less in size. There were seven pN0 cases; one was
      upstaged by additional findings that may have been artifactual. There were four
      pN1 cases; three were upstaged to pN2 after submission of the mesenteric
      material. All four pN2 tumors had additional metastases identified. In all, 75%
      of all positive nodes were under 2.0 mm in size. In this limited sample, standard
      gross dissection proved sufficient for most pN0 tumors to remain node negative.
      However, our findings within the pN1 group show that examination of all of the
      mesenteric material may be necessary to be assured of correct pN status.

PMID- 14976531
TI  - Sequential clinical and histopathological changes in collagenous and lymphocytic
      colitis over time.
AB  - We conducted this retrospective study to evaluate the relationship between
      symptoms, histological findings, and treatment of collagenous (CC) and
      lymphocytic colitis (LC). We identified 19 CC and 12 LC patients having multiple
      colonoscopic procedures with colonic biopsies during their course of illness. A
      detailed histological review of all biopsies was performed. Clinical history,
      including symptoms and medications, was obtained in 25 of the 31 patients and was
      correlated with their histological findings. In all, 25% of the CC patients and
      50% of the LC patients who had biopsies prior to their definitive diagnosis had
      the pathognomonic histological features on their prior biopsies to some extent
      (but were not recognized by the pathologists); however, these features were more
      pronounced on the biopsies from the procedure that established the diagnosis.
      Nonetheless, 10 of 12 such patients with clinical data available had symptoms and
      were being treated at the time of prior biopsies. Assessment of the relationship
      among histological, clinical and therapeutic data showed no association between
      symptoms or histological findings and treatment with any medication. In summary,
      in this sample of CC and LC patients, symptoms often precede fully developed
      histological features. No change in symptoms or histological findings was found
      to be associated with medication.

PMID- 14976532
TI  - Central low-grade osteosarcoma with pagetoid bone formation: a potential
      diagnostic pitfall.
AB  - Central low-grade osteosarcoma is an uncommon form of osteosarcoma, which is
      often difficult to distinguish from benign bone lesions. We reviewed the
      radiographic studies, the histologic material and the clinical records of two
      patients with central low-grade osteosarcoma that closely simulated the
      histologic appearance of Paget's disease of bone. The patients were two women
      aged 46 and 53 years. Radiologically, they presented a large ill-defined densely
      sclerotic lesion involving the proximal tibia. Both lesions only focally
      presented the conventional histologic appearance of central low-grade
      osteosarcoma, with a proliferation of fibroblast-like cells embedded in a dense
      collagenous stroma and irregular anastomosing tumor bone trabeculae. The most
      striking feature was the presence of extremely thickened irregular plates of bone
      with an irregular mosaic pattern of cement lines that closely resembled that of
      Paget's disease of bone. One patient, who had been initially treated for Paget's
      disease for 7 years, experienced disease progression. At resection of proximal
      tibia, there was evidence of dedifferentiation to high-grade osteosarcoma. After
      2 months, she developed local recurrence that was treated with above-knee
      amputation, followed by chemotherapy. She died with multiple lung metastases 4
      months later. The other patient is alive 9 months after wide tumor resection.
      These cases further expand the spectrum of central low-grade osteosarcoma, and
      underscore the diagnostic difficulties in separating central low-grade
      osteosarcoma from benign bone diseases, which may lead to delay in diagnosis,
      inadequate treatment, and eventually to dedifferentiation. Recognition of this
      variant of central low-grade osteosarcoma is based on the aggressive radiologic
      appearance and on adequate tumor sampling for histologic examination.

PMID- 14976533
TI  - Diffuse malignant mesothelioma of the peritoneum and pleura, analysis of markers.
AB  - Diffuse malignant mesothelioma of the peritoneum is a rare diagnosis. Despite
      many histopathologic similarities between peritoneal and pleural tumors, clinical
      and prognostic features may be quite different. There is a paucity of data
      evaluating molecular features of peritoneal mesotheliomas. Therefore, we compared
      the results of a battery of immunohistochemical markers, some with therapeutic
      implications, in patients with primary peritoneal or pleural mesotheliomas. We
      examined 24 peritoneal and nine pleural malignant mesotheliomas with a battery of
      immunohistochemical markers (cytokeratin AE1/3, calretinin, c-kit/CD117, desmin,
      epidermal growth factor receptor (EGFR), estrogen receptors (ER), progesterone
      receptors (PR), MIB-1, and cleaved caspase-3) in an attempt to distinguish any
      differences in this tumor arising in these two distinct locations. The results
      indicate that the only marker to show a significant difference in its staining
      pattern between these two sites was EGFR (P=0.0004). In all, 92% (22/24) of
      peritoneal tumors demonstrated 3+ or 4+ immunoreactivity with EGFR, opposed to
      only 33% (3/9) pleural tumors. There was no significant difference in
      immunoreactivity between the pleural and peritoneal tumors with c-kit, ER, PR,
      cleaved caspase 3, calretinin, and desmin. There was a trend toward increased
      cytokeratin (P=0.07) and MIB-1 (P=0.08) expression in the peritoneal group. There
      was no significant difference in age, sex, or histologic subtype between the two
      locations. In conclusion, despite similarities between peritoneal and pleural
      mesothelioma, there are differences between this neoplasm arising in these two
      sites. The EGFR expression is more pronounced in peritoneal tumors compared to
      pleural tumors. The increased expression of EGFR in the peritoneal lesions may be
      of clinical significance with the recent emergence of epidermal growth factor
      receptor-targeted therapies.

PMID- 14976534
TI  - Immunohistochemical expression of cytokeratins 7 and 20 in malignant salivary
      gland tumors.
AB  - On the basis of the heterogeneity of cytokeratins 7 and 20 expression in
      malignant epithelial tumors, the cytokeratin 7/20 immunophenotype has served as a
      useful diagnostic tool for discrimination of primary and/or metastatic carcinomas
      of unknown origin. However, the expression pattern of these cytokeratins in
      malignant salivary gland tumors has not been thoroughly studied. Our study
      material was composed of 84 malignant tumors of primary major or minor salivary
      gland origin. Nine histologic types of carcinoma were represented, including
      mucoepidermoid (26 cases), adenoid cystic (25), polymorphous low grade (11),
      salivary duct (8), acinic cell (4), ex mixed tumor (3), not otherwise specified
      (3), clear cell (2), and basal cell (2). In all, 13 cases of primary skin or
      mucosal squamous cell carcinoma with secondary salivary gland involvement were
      also examined. Immunoreactivity for cytokeratin 7 was evident in all malignant
      salivary gland tumors; the staining pattern was diffuse and strong in 62 cases,
      and focal and strong in 22 cases. In contrast, 78 cases were negative for
      cytokeratin 20, whereas only six cases (two mucoepidermoid, one adenoid cystic,
      and three salivary duct) displayed focal weak positivity. Overall, 92.9% of
      malignant salivary gland tumors were characterized by a cytokeratin 7 positive/20
      negative immunoprofile, the remaining 7.1% of cases being positive for both
      cytokeratins. The latter phenotype was more common in salivary duct carcinomas
      (P< or =0.05). On the other hand, most squamous cell carcinomas (69%) were
      negative for both cytokeratins, while the remaining cases (31%) were negative for
      cytokeratin 20 and focally weakly positive for cytokeratin 7. We suggest that
      assessment of cytokeratin 7/20 immunoprofile may facilitate the differential
      diagnosis of (a) primary malignant salivary gland tumors from metastatic tumors,
      (b) metastatic salivary gland tumors, (c) primary salivary gland tumors,
      especially mucoepidermoid carcinomas, from squamous cell carcinomas, and (d)
      salivary duct carcinomas from other malignant salivary gland tumors.

PMID- 14976535
TI  - Biological behavior of keratoacanthoma and squamous cell carcinoma: telomerase
      activity and COX-2 as potential markers.
AB  - Distinguishing keratoacanthoma from squamous cell carcinoma is a persistent issue
      in pathology practice. Solitary keratoacanthoma is a self-limiting lesion as
      opposed to rather aggressive clinical behavior of squamous cell carcinoma.
      Several markers were studied to understand their biology and to separate these
      two lesions on a firm basis, but without much success. In this study, we plan to
      utilize recent markers such as telomerase activity and cyclooxygenase-2 (COX-2)
      along with more established marker p53 in understanding the biologic differences
      between keratoacanthoma and squamous cell carcinoma. We studied 17 well to
      moderately differentiated squamous cell carcinoma and 24 early proliferative
      phase keratoacanthoma by immunohistochemistry for the expression of p53 protein,
      COX-2 and telomerase activity. Higher telomerase activity was found in 11/17
      squamous cell carcinoma (65%) compared to 4/24 (17%) of keratoacanthoma.
      Similarly, stronger expression of p53 and COX-2 was detected in 12 (71%) and 11
      (65%) cases of squamous cell carcinoma compared to 2 (8%) and 2 (8%) cases of
      keratoacanthoma respectively. A highly significant 'P' value was obtained for
      telomerase activity (0.001), p53 (0.000), and COX-2 (0.001). Telomerase activity,
      COX-2, and p53 expression provide evidence that keratoacanthoma and squamous cell
      carcinoma are indeed distinct entities and also help in discriminating these two
      lesions, which closely resemble each other on conventional morphology. Although
      these markers present new insights into the biologic variation of keratoacanthoma
      and squamous cell carcinoma, they are of limited value for routine application in
      histological distinction of these two lesions. The differential expression of
      markers also explains the sustained proliferation observed in squamous cell
      carcinoma, compared to a shorter lifespan and involution in keratoacanthoma.

PMID- 14976536
TI  - Superficial pseudoaneurysms: clinicopathologic aspects and involvement of
      extracellular matrix proteoglycans.
AB  - The distribution of proteoglycans in 21 temporal and two ulnar artery
      pseudoaneurysms was studied immunohistochemically. A history of trauma was
      elicited in six cases, and 16 of the lesions were pulsatile. The clinical
      diagnosis was aneurysm or cyst in 18 patients, possible arteritis in two
      patients, tumor in one patient, and unknown in the remaining patient.
      Histologically, there was a prominent myxoid neointimal response in the walls of
      each interrupted artery. The remnant arterial segment was often inconspicuous.
      Prominent smooth muscle cell proliferation and granulation tissue response with
      inflammation led to misdiagnosis of tumor or vasculitis, respectively, in 11
      cases. Immunohistochemical staining for proteoglycans demonstrated abundant,
      diffuse versican in interrupted wall segments. Biglycan was confined to
      collagenized and vascularized areas. In some portions of medial disruption, in
      which angiogenesis was prominent, decorin was expressed within endothelial cells
      of neocapillaries. These findings demonstrate that superficial pseudoaneurysms
      may be mistaken clinically and pathologically for unrelated entities. The
      immunohistochemical studies confirm that versican is upregulated in areas of
      tensile stress. In addition, the presence of endothelial expression of decorin
      supports the concept of decorin's involvement in angiogenesis.

PMID- 14976537
TI  - Simultaneous chromosome 1q gain and 16q loss is associated with steroid receptor
      presence and low proliferation in breast carcinoma.
AB  - We applied comparative genomic hybridization (CGH) to 46 breast carcinoma
      samples, collected from 1993 to 1995, in order to detect chromosome 1q gains and
      16q losses and to define whether samples showing both these alterations had
      distinct biopathologic features and different clinical outcome. A total of 22
      samples (48%) had simultaneous chromosome 1q gain and 16q loss, which was always
      associated with other genetic changes. In total, 23 samples had various
      chromosome imbalances (including chromosome 1q gain independent of chromosome 16q
      loss and vice versa) and one sample did not show detectable alterations. Samples
      having chromosome 1q gain/16q loss were compared to the other samples with regard
      to neoplasm size, lymph-node status, histologic and nuclear grade, estrogen and
      progesterone receptor presence, Ki-67, pRB, Cyclin D1, Cyclin A, p53, p21 and p27
      expression as detected by immunohistochemistry. The samples showing chromosome 1q
      gain/16q loss had high steroid hormone receptor expression (P=0.02), low cell
      growth fraction (Ki-67, P=0.03) and high p27 expression (P<0.001). No statistical
      correlation with disease-free survival and overall survival or response to
      hormonal therapy was found. We conclude that simultaneous chromosome 1q gain/16q
      loss is a frequent event in invasive breast cancer, which occurs in a subset of
      both intermediate- and high-grade breast carcinomas. Although the final
      chromosome 1q and 16q imbalances might have originated from different chromosome
      alterations in low- and high-grade samples, the gene-dosage effect might be
      important in conferring peculiar biopathologic characteristics to this subset of
      samples. The cytogenetic and molecular mechanisms underlying these chromosome
      changes deserve further investigations.

PMID- 14976538
TI  - Molecular characterization of uterine clear cell carcinoma.
AB  - Clinicopathological studies support a broad classification of endometrial
      carcinoma into two major types, designated as type I and type II, which correlate
      with their biological behavior. More recently, molecular studies have provided
      further insights into this classification scheme by elucidating the genetic
      events involved in the development and progression of endometrial carcinoma.
      Microsatellite instability and mutations in the PTEN gene have been widely
      associated with type I (endometrioid) endometrial carcinoma, while p53 mutations
      have been identified in the majority of type II endometrial carcinoma, of which
      uterine serous carcinoma is the prototype. Uterine clear cell carcinoma (UCC) is
      an uncommon variant of endometrial carcinoma, and clinicopathological studies
      have produced conflicting results regarding its biological behavior with 5-year
      survival ranging from 21 to 75%. The molecular characteristics of endometrioid
      and serous carcinoma have been studied extensively; however, there have been few
      molecular genetic studies of the clear cell subtype. In this study, we evaluated
      16 UCCs (11 pure and 5 mixed) for mutations in the p53 gene, PTEN gene and for
      microsatellite instability. Although we found that these alterations were
      uncommon in pure clear cell carcinomas, all three were identified. In addition,
      two cases of mixed serous and clear cell carcinoma showed an identical mutation
      of the p53 gene in the histologically distinct components and one case of mixed
      clear cell and endometrioid carcinoma had identical mutations in the PTEN and p53
      genes, and microsatellite instability in both components. Our data suggest that
      UCC represent a heterogeneous group of tumors that arise via different
      pathogenetic pathways. Additional molecular studies of pure clear cell carcinoma
      are required to further elucidate the genetic pathways involved in its
      development and progression.

PMID- 14976539
TI  - Benign mimickers of prostatic adenocarcinoma.
AB  - The diagnosis of prostatic adenocarcinoma, especially when present in small
      amounts, is often challenging. Before making a diagnosis of carcinoma, it is
      prudent for the pathologist to consider the various benign patterns and processes
      that can simulate prostatic adenocarcinoma. A useful method of classifying benign
      mimickers is in relationship to the major growth patterns depicted in the
      classical Gleason diagram. The four major patterns are small gland, large gland,
      fused gland and solid. Most mimickers fit within the small gland category and the
      most common ones giving rise to false-positive cancer diagnosis are atrophy, post
      atrophic hyperplasia, atypical adenomatous hyperplasia and seminal vesicle-type
      tissue. A number of other histoanatomic structures such as Cowper's gland,
      verumontanum mucosal glands, mesonephric glands and paraganglionic tissue may be
      confused with adenocarcinoma. Additionally, metaplastic and hyperplastic
      processes within the prostate may be confused with adenocarcinoma. Furthermore,
      inflammatory processes including granulomatous prostatitis, xanthogranulomatous
      prostatitis and malakoplakia may simulate high-grade adenocarcinoma. Atypical
      adenomatous hyperplasia (adenosis), a putative precursor of transition zone
      adenocarcinoma, has overlapping features with low-grade adenocarcinoma and may
      cause problems in differential diagnosis, especially in the needle biopsy
      setting. The pathologist's awareness of the vast array of benign mimickers is
      important in the systematic approach to the diagnosis of prostatic
      adenocarcinoma. Knowledge of these patterns on routine microscopy coupled with
      the prudent use of immunohistochemistry will lead to a correct diagnosis and
      avert a false-positive cancer interpretation.

PMID- 14976540
TI  - Gleason grading and prognostic factors in carcinoma of the prostate.
AB  - Gleason grade of adenocarcinoma of the prostate is an established prognostic
      indicator that has stood the test of time. The Gleason grading method was devised
      in the 1960s and 1970s by Dr Donald F Gleason and members of the Veterans
      Administration Cooperative Urological Research Group. This grading system is
      based entirely on the histologic pattern of arrangement of carcinoma cells in H&E
      stained sections. Five basic grade patterns are used to generate a histologic
      score, which can range from 2 to 10. These patterns are illustrated in a standard
      drawing that can be employed as a guide for recognition of the specific Gleason
      grades. Increasing Gleason grade is directly related to a number of
      histopathologic end points, including tumor size, margin status, and pathologic
      stage. Indeed, models have been developed that allow for pretreatment prediction
      of pathologic stage based upon needle biopsy Gleason grade, total serum prostate
      specific antigen level, and clinical stage. Gleason grade has been linked to a
      number of clinical end points, including clinical stage, progression to
      metastatic disease, and survival. Gleason grade is often incorporated into
      nomograms used to predict response to a specific therapy, such as radiotherapy or
      surgery. Needle biopsy Gleason grade is routinely used to plan patient management
      and is also often one of the criteria for eligibility for clinical trials testing
      new therapies. Gleason grade should be routinely reported for adenocarcinoma of
      the prostate in all types of tissue samples. Experimental approaches that could
      be of importance in the future include determination of percentage of high-grade
      Gleason pattern 4 or 5, and utilization of markers discovered by gene expression
      profiling or by genetic testing for DNA abnormalities. Such markers would be of
      prognostic usefulness if they provided added value beyond the established
      indicators of Gleason grade, serum prostate-specific antigen, and stage.
      Currently, established prognostic factors for prostatic carcinoma recommended for
      routine reporting are TNM stage, surgical margin status, serum prostate-specific
      antigen, and Gleason grade.

PMID- 14976541
TI  - Unusual subtypes of prostate cancer.
AB  - The vast majority of prostatic tumors developing in adult males are
      adenocarcinomas. For the most part, variations in histology have not received
      specific designations and, from a practical approach, have had any specific
      prognostic implications handled through application of the Gleason grading
      system. Nonetheless, some of the adenocarcinoma variants have specific clinical
      features and differential diagnoses. Furthermore, there has been some controversy
      regarding the appropriate application of the Gleason grading scheme in these
      tumors. In addition, there are carcinomas that are in fact not adenocarcinomas
      and that should be kept as distinct entities. In this paper, the histologic
      variants of adenocarcinoma are reviewed with emphasis on clinicopathologic
      features and the clinical relevance of these subtypes. Other carcinomas that
      occur in the prostate gland are also discussed again with a focus on the
      clinicopathologic characteristics.

PMID- 14976542
TI  - Retinal dialysis: are we missing diagnostic opportunities?
AB  - AIMS: To review medical records of those patients managed by our department for
      retinal dialysis, and establish whether the initial assessment had been adequate
      to make the diagnosis. That is, to establish if an adequate initial assessment
      had been performed that would reasonably exclude the likelihood of retinal
      dialysis and other trauma-related sequelae such as angle recession. METHODS: A
      retrospective review was made of all patients managed for retinal dialysis at
      Sussex Eye Hospital between 20 March 1997 and 20 September 2002 (66 months). In
      addition to general demographic data, surgical management and outcome, patient
      files were reviewed for history of trauma, prior ophthalmic review, and whether
      such review included documentation of peripheral retinal examination and
      gonioscopy. RESULTS: A total of 580 primary procedures were performed for retinal
      detachment during the review period, of which 32 eyes of 29 patients underwent
      surgery for retinal dialysis (6%). There were 21 male and eight female patients,
      with a history of trauma obtained in 55% (17 eyes, 16 patients). Of the 16
      patients with prior trauma, nine had undergone prior ophthalmic review at the
      time or soon after their trauma; however, only 2 (22%) had documented evidence of
      indented peripheral retinal examination. Only one (3%) patient in the whole
      series had documented gonioscopy. CONCLUSIONS: Patients with history of trauma
      often present at the time or soon after their injury (eg hyphaema, orbital
      fractures). Thus, an opportunity exists to screen patients for known sequelae of
      trauma such as retinal dialysis and angle recession. It was disappointing to
      learn that this opportunity was not always being utilized, with some patients
      consequently developing macula-off retinal detachments and potential for reduced
      visual outcome.

PMID- 14976543
TI  - Horner's syndrome as manifestation of Wegener's granulomatosis.

PMID- 14976544
TI  - Eyelid sebaceous gland carcinoma (SGC) treated with 'slow' Mohs' micrographic
      surgery.

PMID- 14976545
TI  - Recurrence of giant pseudocyst in advanced bullous keratopathy.

PMID- 14976546
TI  - Does cardiovascular therapy affect the onset and recurrence of preretinal and
      vitreous haemorrhage in diabetic eye disease?
AB  - AIMS: To review the role of cardiovascular disease and therapy in the onset and
      recurrence of preretinal/vitreous haemorrhage in diabetic patients. METHODS:
      Retrospective case note analysis of diabetic patients with vitreous haemorrhage
      from the Diabetic Eye Clinic at Birmingham Heartlands Hospital. RESULTS: In
      total, 54 patients (mean age 57.1, 37 males, 20 type I vs 34 type II diabetic
      patients) were included. The mean (SD) duration of diagnosed diabetes at first
      vitreous haemorrhage was significantly longer, 21.9 (7.6) years for type I and
      14.8 (9.3) years for type II diabetic patients (P < 0.01, unpaired t-test, two
      tailed).Aspirin administration was not associated with a significantly later
      onset of vitreous haemorrhage. Four episodes were associated with ACE-inhibitor
      cough. There was a trend towards HMGCoA reductase inhibitor (statin) use being
      associated with a delayed onset of vitreous haemorrhage: 21.4 years until
      vitreous haemorrhage (treatment group) vs 16.2 years (nontreatment group) (P =
      0.09, two-tailed, unpaired t-test, not statistically significant). During follow
      up 56 recurrences occurred, making a total of 110 episodes of vitreous
      haemorrhage in 79 eyes of 54 patients. The mean (range) follow-up post
      haemorrhage was 1067 (77-3842) days, with an average of 1.02 recurrences. Age,
      gender, diabetes type (I or II) or control, presence of hypertension or
      hypercholesterolaemia, and macrovascular complications were not associated with a
      significant effect on the 1-year recurrence rate. Aspirin (and other antiplatelet
      or anticoagulant agents) and ACE- inhibitors appeared to neither increase nor
      decrease the 1-year recurrence rate. However, statin use was significantly
      associated with a reduction in recurrence (Fisher exact P < 0.05; two-tailed)
      with an odds ratio (95% CI) of 0.25 (0.1-0.95). CONCLUSION: In this retrospective
      analysis, the onset of preretinal/vitreous haemorrhage was not found to be
      accelerated by gender, hypertension, hypercholesterolaemia, evidence of
      macrovascular disease, or HbA1c. Neither aspirin nor ACE-inhibitor administration
      accelerated the onset or recurrence of first vitreous haemorrhage. Statins may
      have a protective role, both delaying and reducing the recurrence of haemorrhage.

PMID- 14976547
TI  - Management and outcome of sight-threatening diabetic retinopathy in pregnancy.
AB  - AIMS: To report the management and outcomes of sight-threatening diabetic
      retinopathy in pregnancy. METHODS: A retrospective review of 8 diabetic females
      who developed pregnancy related sight-threatening diabetic retinopathy requiring
      treatment over a 12-year period. RESULTS: In total, 16 eyes of eight patients
      were included in this series. The mean age of the patients at presentation was
      30.75 years +/-3.8 SD and the mean duration of diabetes was 21.0 years +/-5.1 SD.
      The mean follow-up period was 46.75 months +/-47.2 SD. A total of 87.5% of
      patients showed progression of diabetic retinopathy during pregnancy, 71% of
      which were in the sight-threatening proliferative category. In the postpartum
      period, 81% of patients continued to progress to proliferative diabetic
      retinopathy, requiring panretinal photocoagulation and multiple other surgical
      procedures. In all, 69% of eyes retained visual acuity equal to or better than
      0.3 logMAR units (6/12). CONCLUSION: Sight-threatening diabetic retinopathy in
      pregnancy is a rare disease, but it can have devastating consequences for mother
      and child. Laser photocoagulation should be considered for pregnant women with
      severe preproliferative diabetic retinopathy. Proliferative diabetic retinopathy
      may not regress postpartum. Close followup should be extended in the postpartum
      period in this group of patients until the retinopathy is stabilised. The
      presence of combined rhegmatogenous and tractional retinal detachment and
      neovascular glaucoma were associated with the worst outcome.

PMID- 14976548
TI  - Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to
      mesenchymal transition.
AB  - Epithelial-to-mesenchymal transitions (EMTs) underlie cell plasticity required in
      embryonic development and frequently observed in advanced carcinogenesis.
      Transforming growth factor-beta (TGF-beta) induces EMT phenotypes in epithelial
      cells in vitro and has been associated with EMT in vivo. Here we report that
      expression of the hairy/enhancer-of-split-related transcriptional repressor Hey1,
      and the Notch-ligand Jagged1 (Jag1), was induced by TGF-beta at the onset of EMT
      in epithelial cells from mammary gland, kidney tubules, and epidermis. The HEY1
      expression profile was biphasic, consisting of immediate-early Smad3-dependent,
      Jagged1/Notch-independent activation, followed by delayed, indirect Jagged1/Notch
      dependent activation. TGF-beta-induced EMT was blocked by RNA silencing of HEY1
      or JAG1, and by chemical inactivation of Notch. The EMT phenotype, biphasic
      activation of Hey1, and delayed expression of Jag1 were induced by TGF-beta in
      wild-type, but not in Smad3-deficient, primary mouse kidney tubular epithelial
      cells. Our findings identify a new mechanism for functional integration of
      Jagged1/Notch signalling and coordinated activation of the Hey1 transcriptional
      repressor controlled by TGF-beta/Smad3, and demonstrate functional roles for
      Smad3, Hey1, and Jagged1/Notch in mediating TGF-beta-induced EMT.

PMID- 14976549
TI  - Molecular mechanism of RNA silencing suppression mediated by p19 protein of
      tombusviruses.
AB  - RNA silencing is an evolutionarily conserved surveillance system that occurs in a
      broad range of eukaryotic organisms. In plants, RNA silencing acts as an
      antiviral system; thus, successful virus infection requires suppression of gene
      silencing. A number of viral suppressors have been identified so far; however,
      the molecular bases of silencing suppression are still poorly understood. Here we
      show that p19 of Cymbidium ringspot virus (CymRSV) inhibits RNA silencing via its
      small RNA-binding activity in vivo. Small RNAs bound by p19 in planta are bona
      fide double-stranded siRNAs and they are silencing competent in the in vitro RNA
      silencing system. p19 also suppresses RNA silencing in the heterologous
      Drosophila in vitro system by preventing siRNA incorporation into RISC. During
      CymRSV infection, p19 markedly diminishes the amount of free siRNA in cells by
      forming p19-siRNA complexes, thus making siRNAs inaccessible for effector
      complexes of RNA-silencing machinery. Furthermore, the obtained results also
      suggest that the p19-mediated sequestration of siRNAs in virus-infected cells
      blocks the spread of the mobile, systemic signal of RNA silencing.

PMID- 14976550
TI  - Domain movements of elongation factor eEF2 and the eukaryotic 80S ribosome
      facilitate tRNA translocation.
AB  - An 11.7-A-resolution cryo-EM map of the yeast 80S.eEF2 complex in the presence of
      the antibiotic sordarin was interpreted in molecular terms, revealing large
      conformational changes within eEF2 and the 80S ribosome, including a
      rearrangement of the functionally important ribosomal intersubunit bridges.
      Sordarin positions domain III of eEF2 so that it can interact with the sarcin
      ricin loop of 25S rRNA and protein rpS23 (S12p). This particular conformation
      explains the inhibitory action of sordarin and suggests that eEF2 is stalled on
      the 80S ribosome in a conformation that has similarities with the GTPase
      activation state. A ratchet-like subunit rearrangement (RSR) occurs in the
      80S.eEF2.sordarin complex that, in contrast to Escherichia coli 70S ribosomes, is
      also present in vacant 80S ribosomes. A model is suggested, according to which
      the RSR is part of a mechanism for moving the tRNAs during the translocation
      reaction.

PMID- 14976551
TI  - Impairment of p53 acetylation, stability and function by an oncogenic
      transcription factor.
AB  - Mutations of p53 are remarkably rare in acute promyelocytic leukemias (APLs).
      Here, we demonstrate that the APL-associated fusion proteins PML-RAR and PLZF-RAR
      directly inhibit p53, allowing leukemic blasts to evade p53-dependent cancer
      surveillance pathways. PML-RAR causes deacetylation and degradation of p53,
      resulting in repression of p53 transcriptional activity, and protection from p53
      dependent responses to genotoxic stress. These phenomena are dependent on the
      expression of wild-type PML, acting as a bridge between p53 and PML-RAR.
      Recruitment of histone deacetylase (HDAC) to p53 and inhibition of p53 activity
      were abrogated by conditions that either inactivate HDACs or trigger HDAC release
      from the fusion protein, implicating recruitment of HDAC by PML-RAR as the
      mechanism underlying p53 inhibition.

PMID- 14976552
TI  - LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily,
      including MARK/PAR-1.
AB  - We recently demonstrated that the LKB1 tumour suppressor kinase, in complex with
      the pseudokinase STRAD and the scaffolding protein MO25, phosphorylates and
      activates AMP-activated protein kinase (AMPK). A total of 12 human kinases
      (NUAK1, NUAK2, BRSK1, BRSK2, QIK, QSK, SIK, MARK1, MARK2, MARK3, MARK4 and MELK)
      are related to AMPK. Here we demonstrate that LKB1 can phosphorylate the T-loop
      of all the members of this subfamily, apart from MELK, increasing their activity
      >50-fold. LKB1 catalytic activity and the presence of MO25 and STRAD are required
      for activation. Mutation of the T-loop Thr phosphorylated by LKB1 to Ala
      prevented activation, while mutation to glutamate produced active forms of many
      of the AMPK-related kinases. Activities of endogenous NUAK2, QIK, QSK, SIK,
      MARK1, MARK2/3 and MARK4 were markedly reduced in LKB1-deficient cells. Neither
      LKB1 activity nor that of AMPK-related kinases was stimulated by phenformin or
      AICAR, which activate AMPK. Our results show that LKB1 functions as a master
      upstream protein kinase, regulating AMPK-related kinases as well as AMPK. Between
      them, these kinases may mediate the physiological effects of LKB1, including its
      tumour suppressor function.

PMID- 14976553
TI  - Structure of the La motif: a winged helix domain mediates RNA binding via a
      conserved aromatic patch.
AB  - The La protein is a ubiquitous nuclear phosphoprotein that recognizes the 3'
      uridylates found in all newly synthesized RNA polymerase III transcripts. La
      binding stabilizes these transcripts from exonucleases and may also assist their
      folding. Here we present the first structural insights into how the La protein
      specifically interacts with its RNA substrates. The most conserved region of the
      La protein is the La motif, a domain also found in several other RNA-binding
      proteins. We have determined the structure of the La motif from the Trypanosoma
      brucei La protein to 1.6 A resolution (PDB code 1S29). The La motif adopts a
      winged helix-turn-helix architecture that has a highly conserved patch of mainly
      aromatic surface residues. Mutagenesis experiments support a critical role for
      this patch in RNA binding and show that it partly determines binding specificity
      for RNAs ending in 3' hydroxyl, a defining characteristic of the La protein.
      These findings reveal that the La motif is essential for high-affinity binding
      and also contributes to specificity.

PMID- 14976554
TI  - Functions of eIF3 downstream of 48S assembly impact AUG recognition and GCN4
      translational control.
AB  - The binding of eIF2-GTP-tRNA(i)(Met) ternary complex (TC) to 40S subunits is
      impaired in yeast prt1-1 (eIF3b) mutant extracts, but evidence is lacking that TC
      recruitment is a critical function of eIF3 in vivo. If TC binding was rate
      limiting in prt1-1 cells, overexpressing TC should suppress the temperature
      sensitive phenotype and GCN4 translation should be strongly derepressed in this
      mutant, but neither was observed. Rather, GCN4 translation is noninducible in
      prt1-1 cells, and genetic analysis indicates defective ribosomal scanning between
      the upstream open reading frames that mediate translational control. prt1-1 cells
      also show reduced utilization of a near-cognate start codon, implicating eIF3 in
      AUG selection. Using in vivo cross-linking, we observed accumulation of TC and
      mRNA/eIF4G on 40S subunits and a 48S 'halfmer' in prt1-1 cells. Genetic evidence
      suggests that 40S-60S subunit joining is not rate-limiting in the prt1-1 mutant.
      Thus, eIF3b functions between 48S assembly and subunit joining to influence AUG
      recognition and reinitiation on GCN4 mRNA. Other mutations that disrupt eIF2-eIF3
      contacts in the multifactor complex (MFC) diminished 40S-bound TC, indicating
      that MFC formation enhances 43S assembly in vivo.

PMID- 14976555
TI  - Modulation of kinesin binding by the C-termini of tubulin.
AB  - The flexible tubulin C-terminal tails (CTTs) have recently been implicated in the
      walking mechanism of dynein and kinesin. To address their role in the case of
      conventional kinesin, we examined the structure of kinesin-microtubule (MT)
      complexes before and after CTT cleavage by subtilisin. Our results show that the
      CTTs directly modulate the motor-tubulin interface and the binding properties of
      motors. CTT cleavage increases motor binding stability, and kinesin appears to
      adopt a binding conformation close to the nucleotide-free configuration under
      most nucleotide conditions. Moreover, C-terminal cleavage results in trapping a
      transient motor-ADP-MT intermediate. Using SH3-tagged dimeric and monomeric
      constructs, we could also show that the position of the kinesin neck is not
      affected by the C-terminal segments of tubulin. Overall, our study reveals that
      the tubulin C-termini define the stability of the MT-kinesin complex in a
      nucleotide-dependent manner, and highlights the involvement of tubulin in the
      regulation of weak and strong kinesin binding states.

PMID- 14976556
TI  - DNA damage induces downregulation of histone gene expression through the G1
      checkpoint pathway.
AB  - Activation of the G(1) checkpoint following DNA damage leads to inhibition of
      cyclin E-Cdk2 and subsequent G(1) arrest in higher eucaryotes. Little, however,
      is known about the molecular events downstream of cyclin E-Cdk2 inhibition. Here
      we show that, in addition to the inhibition of DNA synthesis, ionizing radiation
      induces downregulation of histone mRNA levels in mammalian cells. This
      downregulation occurs at the level of transcription and requires functional p53
      and p21(CIP1/WAF1) proteins. We demonstrate that DNA damage induced by ionizing
      radiation results in the suppression of phosphorylation of NPAT, an in vivo
      substrate of cyclin E-Cdk2 kinase and an essential regulator of histone gene
      transcription, and its dissociation from histone gene clusters in a p53/p21
      dependent manner. Inhibition of Cdk2 activity by specific inhibitors in the
      absence of DNA damage similarly disperses NPAT from histone gene clusters and
      represses histone gene expression. Our results thus suggest that inhibition of
      Cdk2 activity following DNA damage results in the downregulation of histone gene
      transcription through dissociation of NPAT from histone gene clusters.

PMID- 14976557
TI  - The Zap1 transcriptional activator also acts as a repressor by binding downstream
      of the TATA box in ZRT2.
AB  - The zinc-responsive transcriptional activator Zap1 regulates the expression of
      both high- and low-affinity zinc uptake permeases encoded by the ZRT1 and ZRT2
      genes. Zap1 mediates this response by binding to zinc-responsive elements (ZREs)
      located within the promoter regions of each gene. ZRT2 has a remarkably different
      expression profile in response to zinc compared to ZRT1. While ZRT1 is maximally
      induced during zinc limitation, ZRT2 is repressed in low zinc but remains induced
      upon zinc supplementation. In this study, we determined the mechanism underlying
      this paradoxical Zap1-dependent regulation of ZRT2. We demonstrate that a
      nonconsensus ZRE (ZRT2 ZRE3), which overlaps with one of the ZRT2 transcriptional
      start sites, is essential for repression of ZRT2 in low zinc and that Zap1 binds
      to ZRT2 ZRE3 with a low affinity. The low-affinity ZRE is also essential for the
      ZRT2 expression profile. These results indicate that the unusual pattern of ZRT2
      regulation among Zap1 target genes involves the antagonistic effect of Zap1
      binding to a low-affinity ZRE repressor site and high-affinity ZREs required for
      activation.

PMID- 14976558
TI  - Tyrosine phosphorylation of GluR2 is required for insulin-stimulated AMPA
      receptor endocytosis and LTD.
AB  - The alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype of
      glutamate receptors is subject to functionally distinct constitutive and
      regulated clathrin-dependent endocytosis, contributing to various forms of
      synaptic plasticity. In HEK293 cells transiently expressing GluR1 or GluR2
      mutants containing domain deletions or point mutations in their intracellular
      carboxyl termini (CT), we found that deletion of the first 10 amino acids (834
      843) selectively reduced the rate of constitutive AMPA receptor endocytosis,
      whereas truncation of the last 15 amino acids of the GluR2 CT, or point mutation
      of the tyrosine residues in this region, only eliminated the regulated (insulin
      stimulated) endocytosis. Moreover, in hippocampal slices, both insulin treatment
      and low-frequency stimulation (LFS) specifically stimulated tyrosine
      phosphorylation of the GluR2 subunits of native AMPA receptors, and the enhanced
      phosphorylation appears necessary for both insulin- and LFS-induced long-term
      depression of AMPA receptor-mediated excitatory postsynaptic currents. Thus, our
      results demonstrate that constitutive and regulated AMPA receptor endocytosis
      requires different sequences within GluR CTs and tyrosine phosphorylation of
      GluR2 CT is required for the regulated AMPA receptor endocytosis and hence the
      expression of certain forms of synaptic plasticity.

PMID- 14976561
TI  - Severe acute respiratory syndrome (SARS) - an emerging infection of the 21st
      century.
AB  - Severe acute respiratory syndrome (SARS) is an emerging infection caused by a
      novel coronavirus known as SARS-CoV. The disease has a high propensity to spread
      to household members and healthcare workers and may be associated with
      transmission and outbreaks in the community. Severe illness in immunocompromised
      patients, sophisticated hospital facilities and treatment procedures,
      particularly those that generate aerosols, and lack of adequate isolation and
      control measures, can amplify transmission and contribute to so-called "super
      spreading" events. The presence of non-specific clinical manifestations at
      presentation and a lack of validated early diagnostic methods and effective
      management pose great difficulty for frontline physicians in the containment of
      this disease. The mortality of SARS is in the region of 10 to 15%; the presence
      of underlying disease, high initial C-reactive protein levels, and positive SARS
      CoV in nasopharyngeal aspirate samples are associated with a higher risk of
      respiratory failure and mortality. Despite the disappearance of SARS cases
      worldwide, the potential evolution of SARS-CoV in animals suggests the disease
      may re-emerge in the future. Heightened levels of clinical suspicion, rapid case
      detection and isolation, and contact tracing are essential to effective
      management of future outbreaks. Further ongoing requirements for successful
      management include research on the immunopathogenesis of SARS and the development
      of timely and reliable diagnostic tests, effective antiviral and immunomodulatory
      agents, and vaccines for the disease.

PMID- 14976559
TI  - Localization of Tec29 to ring canals is mediated by Src64 and PtdIns(3,4,5)P3
      dependent mechanisms.
AB  - Two tyrosine kinases, Src64 and Tec29, regulate the growth of actin rich-ring
      canals in the Drosophila ovary. We have shown previously that Src64 directs the
      localization of Tec29 to ring canals, but the mechanism underlying this process
      was unknown. Here, we show that Tec29 localizes to ring canals via its Src
      homology 3 (SH3) and Src homology 2 (SH2) domains. Tec29 activity is required for
      its own ring canal localization, suggesting that a phosphotyrosine ligand for the
      SH2 domain is generated by Tec29 itself. Src64 regulates this process by
      phosphorylating Y677 within the kinase domain of Tec29, an event required for
      Tec29 activation. We also show that the pleckstrin homology (PH) domain of Tec29
      has dual functions in mediating Src64 regulation. In the absence of Src64, the PH
      domain prevents Tec29 ring canal localization. In the presence of Src64, it
      enhances membrane targeting of Tec29 by a PI(3,4,5)P(3)-mediated mechanism. In
      the absence of its PH domain, Tec29 constitutively localizes to ring canals, but
      still requires Src64 for full activation.

PMID- 14976562
TI  - Development of multifocal duodenal erosions after anti-Helicobacter pylori triple
      therapy.
AB  - BACKGROUND AND PURPOSE: Anti-Helicobacter pylori triple therapy is effective for
      healing duodenal ulcer (DU) diseases and reducing disease recurrence. However,
      multifocal duodenal erosions or shallow ulcers may develop after triple therapy.
      The purpose of this study was to investigate the incidence and outcome of
      duodenal erosions that developed after triple therapy. METHODS: A total of 106
      Taiwanese with active DU and with H. pylori infection were enrolled in this
      study. All patients received anti-H. pylori triple therapy (i.e., 2 weeks of
      antimicrobial agents combined with treatment for 4 to 6 weeks with acid
      suppression agents). Follow-up endoscopy was performed immediately after stopping
      treatment. The incidence of multifocal erosions or shallow ulcers over the bulb
      and/or second portion of the duodenum was studied. Additional acid suppression
      agent was given for 4 weeks whenever duodenal erosions or shallow ulcers were
      found. RESULTS: Out of 106 patients, 11 (10.4%) were found to have multifocal
      duodenal erosions and/or shallow ulcers on the duodenal bulb and/or second
      portion of the duodenum at the end of treatment. Ten of the 11 patients with
      newly developed erosions had healed DU in the S1 or S2 stage, and all 11 had
      successful H. pylori eradication. The duodenal erosions and/or shallow ulcers of
      these 11 patients were healed after an additional 4 weeks of histamine-2-receptor
      antagonist therapy. CONCLUSIONS: Multifocal duodenal erosions and/or shallow
      ulcers were noted in around 10% of Taiwanese DU patients who received anti-H.
      pylori triple therapy. An additional 4 weeks therapy with acid suppression agents
      healed these lesions.

PMID- 14976563
TI  - Favorable outcome of parapneumonic empyema in children managed by primary video
      assisted thoracoscopic debridement.
AB  - BACKGROUND AND PURPOSE: The appropriate type of intervention for the treatment of
      empyema in children remains controversial. This study analyzed whether video
      assisted thoracoscopic debridement (VATD) as first-line treatment is effective in
      the management of pediatric parapneumonic empyema. METHODS: We retrospectively
      reviewed the medical and microbiological records of pediatric patients with
      parapneumonic empyema diagnosed at a medical center from January 1995 to December
      2002. The 55 patients included in this study were initially treated with either
      tube thoracostomy drainage (TTD group [n = 37]) or video-assisted thoracoscopic
      debridement (VATD group [n = 18]). RESULTS: A comparative analysis found no
      significant difference in patient characteristics between these 2 groups.
      Patients in the VATD group had a significantly shorter duration of fever (18.9 +/
      1.7 vs 26.9 +/- 1.3 days), chest tube placement (5.3 +/- 0.7 vs 15.2 +/- 2.0
      days), antibiotic therapy after the procedure (12.2 +/- 1.0 vs 26.3 +/- 2.8
      days), and hospital stay (21.5 +/- 2.1 vs 33.2 +/- 2.8 days). No additional
      procedures were required in the VATD group, whereas 65% (24/37) of patients in
      the TTD group underwent salvage VATD. CONCLUSION: Primary management using video
      assisted thoracoscopic decortication was more effective and reduced the duration
      of illness in pediatric patients with parapneumonic empyema.

PMID- 14976564
TI  - Phenotype and genotype analyses of ornithine transcarbamylase deficiency in
      Taiwanese.
AB  - BACKGROUND AND PURPOSE: Ornithine transcarbamylase (OTC) deficiency is the most
      common inherited urea cycle disorder. It is an X-linked semidominant disease with
      variable severity affecting both males and females. The characteristics and
      course have not been assessed in Taiwanese. This study analyzed the phenotype and
      genotype of OTC deficiency in Taiwanese. METHODS: During the period from January
      1993 to December 2001 inclusive, 8 patients had the diagnosis of OTC deficiency
      by the criteria of hyperammonemia, hypocitrullinemia, and orotic aciduria. All 10
      exons of the OTC gene were analyzed for mutations. RESULTS: Among the 8 cases, 3
      belonged to the early-onset group (initial symptoms before or equal to age 28
      days) and 5 belonged to the late-onset group (median onset age, 18 months; range,
      8 months to 52 years). One case in the former group, and 4 cases in the latter
      group survived (mean survival, 8.2 years; range, 3 to 16 years). The average time
      between initial symptoms and diagnosis was 60 months in the late-onset group.
      Analysis of the OTC genes detected 5 different mutations in 5 patients, including
      3 novel mutations: 42delT, 652G>A, and 791C>A. IQ tests, conducted in 3 patients,
      revealed low scores (mean, 53; range, 40 to 72). CONCLUSIONS: Both early-onset
      and late-onset cases of OTC deficiency were identified in Taiwanese. The
      diagnosis was delayed in these patients, and their outcomes were poor. All
      mutations detected were different and most of them have not been reported in
      other populations, which may explain the variability of phenotypes in Taiwanese
      patients.

PMID- 14976565
TI  - Comparison of rabeprazole-based four- and seven-day triple therapy and omeprazole
      based seven-day triple therapy for Helicobacter pylori infection in patients with
      peptic ulcer.
AB  - BACKGROUND AND PURPOSE: Rabeprazole is a new proton pump inhibitor producing
      rapid inhibition of gastric acid secretion. This may potentiate the inhibitory
      effect of antibiotics against Helicobacter pylori. This study compared the
      efficacy, safety, and tolerability of 4- and 7-day rabeprazole-based triple
      therapies versus 7-day omeprazole-based triple therapy. METHODS: A total of 70 H.
      pylori-infected peptic ulcer patients were randomly assigned to 1 of 3 groups:
      RAC4 (rabeprazole 20 mg, amoxicillin 1000 mg, and clarithromycin 500 mg twice
      daily for 4 days), RAC7 (rabeprazole 20 mg, amoxicillin 1000 mg, and
      clarithromycin 500 mg twice daily for 7 days), and OAC7 (omeprazole 20mg,
      amoxicillin 1000 mg, and clarithromycin 500 mg twice daily for 7 days).
      Endoscopy, Campylobacter-like organism (CLO) test, H. pylori culture, and 13C
      urea breath test were performed before randomization and 8 weeks after the start
      of triple therapy. RESULTS: Intention-to-treat (ITT) eradication rates for the
      RAC4, RAC7, and OAC7 groups were 87% (20/23), 83%(19/23), and 88% (21/24),
      respectively, and per-protocol (PP) eradication rates were 91% (20/22), 95%
      (19/20), and 100% (21/21), respectively. There was no significant difference
      among the ITT or PP eradication rates of the 3 groups. All 3 regimens were well
      tolerated and compliance was excellent. CONCLUSIONS: One-week RAC and 1-week OAC
      are equally effective for H. pylori eradication in peptic ulcer patients. The
      duration of RAC triple therapy can be shortened to 4 days without compromising
      its efficacy.

PMID- 14976566
TI  - Sirolimus add-on rescue therapy can benefit patients with chronic renal allograft
      dysfunction.
AB  - BACKGROUND AND PURPOSE: Nephrotoxicity caused by calcineurin inhibitors (CNIs)
      contributes to chronic renal allograft dysfunction (CRAD). This retrospective
      cohort study evaluated the immunosuppressive and nephrotoxic effects of sirolimus
      add-on therapy with minimization of CNI in patients with CRAD. METHODS: Twenty
      patients with CRAD were recruited to receive sirolimus add-on rescue (SRL-AR)
      therapy. The SRL-AR therapy added 6 mg of sirolimus for loading and 2 mg/day for
      maintenance to CNI-based maintenance immunosuppressive regimens and reduced the
      dose of CNI, either cyclosporine or tacrolimus, by half at the initiation of
      sirolimus loading. The primary endpoint of the study was estimated glomerular
      filtration rate (GFR) determined using the Cockcroft-Gault formula. The efficacy
      of this SRL-AR therapy was evaluated by comparison to a historic group of 30
      patients with CRAD who received a tacrolimus-based rescue therapy. RESULTS: Of
      the 20 patients receiving sirolimus therapy, 2 had graft failure during the 12
      month follow-up. The post-rescue GFR values of the patients receiving sirolimus
      therapy showed greater improvement than those of the historic group during follow
      up except for month 8, with the differences in GFR changes reaching significance
      at months 1 to 5 (p < 0.05). Multiple regression analysis identified graft age
      and GFR upon rescue in addition to the SRL-AR therapy as significant factors
      associated with post-rescue GFR changes. CONCLUSIONS: This study demonstrated
      that SRL-AR therapy combined with reduced CNI doses could effectively improve
      short-term renal function of patients with CRAD. The long-term outcome of
      rescuing CRAD is likely to depend on factors including graft age and GFR upon
      rescue.

PMID- 14976567
TI  - Surgical management of hemangioblastomas of the spinal cord.
AB  - BACKGROUND AND PURPOSE: Intramedullary hemangioblastomas are relatively rare
      intraspinal tumors. Total removal of these tumors without causing significant
      neurological deficit remains a great challenge. This study analyzed the
      preoperative characteristics, management, and outcome in patients with successful
      total removal of spinal intramedullary hemangioblastomas. METHODS: Data from the
      medical records of patients with intraspinal hemangioblastomas treated from 1993
      to 2003 were reviewed. The neurological function of these patients was graded and
      the preoperative data were recorded and correlated with clinical outcome.
      RESULTS: Ten patients with spinal intramedullary hemangioblastomas underwent
      microsurgical resection by the same neurosurgeon during the 10-year study period.
      They included 3 men and 7 women with age ranging from 20 to 49 years, with a mean
      age of 33 years. Five of the patients met the diagnostic criteria for von Hippel
      Lindau disease. Preoperative neurological function was grade I in 6 patients,
      grade II in 3 patients and grade III in 1 patient. Immediate postoperative
      neurological function was worse in 3 cases, but all of these patients recovered
      their preoperative function within 3 weeks. At 3 months' follow-up, 9 patients
      had achieved functional grade I, and 1 patient with preoperative grade III
      function had improved to grade II. CONCLUSIONS: Detailed preoperative evaluation
      and skillful microsurgery are mandatory in successful total removal of
      intramedullary hemangioblastomas. The management of spinal hemangioblastomas
      associated with von Hippel-Lindau disease requires a cautious observation of
      clinical course and timely surgical intervention of symptomatic lesions to avoid
      possible neurological deficit.

PMID- 14976568
TI  - Odontoma: a clinicopathologic study of 81 cases.
AB  - BACKGROUND AND PURPOSE: Odontoma is the most common odontogenic tumor. It
      includes 2 types, the compound and complex odontomas. There has not been a series
      study of the clinical and histologic features of odontomas from Taiwan. This
      study evaluated the clinicopathologic features of odontoma in Taiwanese. METHODS:
      Cases of odontoma treated from 1998 to 2002 identified from medical records were
      included. The microscopic features, radiographic features, and clinical history
      of the patients were reviewed and analyzed. RESULTS: A total of 81 odontomas in
      81 patients (36 males and 45 females) were included. There were 62 compound and
      19 complex odontomas. The mean age of the patients was 18 years with the majority
      of odontomas occurring in the first (32%) and second decade (38%) of life.
      Odontomas had a marked predilection for the maxilla (70%) and for the anterior
      region of the jaw (83%), particularly for the anterior maxilla (62%). Sixty four
      (79%) of the 81 odontomas were associated with 80 impacted teeth, including 71
      permanent teeth, 2 deciduous teeth, and 7 supernumerary teeth. Of the 71 impacted
      permanent teeth, the maxillary central incisor (27%) was most commonly affected,
      followed by the maxillary canine (26%) and mandibular canine (24%). Histologic
      examination revealed enamel matrix in 90%, dentin in 100%, cementum in 88%, pulp
      tissue in 96%, fibrous capsule in 93%, ghost cells in 83%, reduced enamel
      epithelium in 86%, and nests of odontogenic epithelium in 58% of odontomas.
      Dentigerous cyst was associated with 9% of odontomas. CONCLUSIONS: In this
      series, odontomas occurred most often in the first and second decade of life.
      Although complex odontomas are usually found in the posterior jaw, in this
      Taiwanese series they were most commonly found in the anterior maxilla. Odontoma
      is frequently associated with an impacted tooth and occasionally with a
      dentigerous cyst. No recurrence of odontomas was found after surgical excision
      with follow-up of 1 to 15 years.

PMID- 14976569
TI  - Permanent neonatal diabetes mellitus manifesting as diabetic ketoacidosis.
AB  - Neonatal diabetes mellitus (NDM) is a very rare disease defined as hyperglycemia
      that occurs during the first month of life, requires insulin treatment, and lasts
      more than 2 weeks. There are 2 types of NDM: permanent neonatal diabetes mellitus
      (PNDM) and transient neonatal diabetes mellitus (TNDM). We report a case of PNDM
      in a 3-day-old female infant. This full-term neonate was born small for
      gestational age. Respiratory distress, poor activity, hypothermia, poor feeding,
      dehydration, and ketoacidosis were noted at the age of 3 days. After insulin
      therapy and fluid replacement, her condition became stable. Glucagon test done at
      the age of 26 days showed serum C-peptide level to be low for her age. During the
      first year of life she had catch-up growth, but insulin therapy was still
      required. Serum C-peptide level was undetectable at the age of 15 months. The
      course of this case indicates the importance of a high index of suspicion for
      patients with PNDM in order to correct metabolic derangement as early as possible
      and facilitate normal growth and development under insulin therapy.

PMID- 14976570
TI  - Chromosomal 10Q26 trisomy resulting from paternal T(9;10)(PTER;Q26.1).
AB  - Distal 10q trisomy is a well defined but rare syndrome, and almost always the
      result of an unbalanced translocation. Clinical evaluation and cytogenetic
      molecular analyses were performed in a 6-year-old boy with developmental delay
      and facial dysmorphism including marked blepharophimosis. His karyotype showed an
      unbalanced translocation between chromosomes 9 and 10, resulting in trisomy of
      the distal part of the long arm of chromosome 10q26. A balanced translocation of
      the segment between chromosomes 9 and 10 with breakpoints at 10q26.1 and 9pter or
      p24.3 was found in his father, who had normal phenotype. Unlike most cases of
      partial 10q trisomy which have concurrent partial monosomy of one other
      translocated chromosome, fluorescence in situ hybridization studies revealed this
      case to be a pure 10q26 trisomy. The translocated 10q segments in most cases of
      10q trisomy originate from the father. Imprinting effect may exist in this
      chromosomal syndrome; distal 10q trisomy from paternal reciprocal translocations
      is more compatible with life.

PMID- 14976571
TI  - Appendicitis complicated by hemoperitoneum.
AB  - Differential diagnosis of acute appendicitis in women of childbearing age is a
      challenge because of the range of gynecologic and obstetric problems with similar
      manifestations. We report a case of acute appendicitis with the rarely
      encountered complication of hemoperitoneum in a sexually active 32-year-old
      woman. The patient presented with right lower quadrant pain and a positive
      culdocentesis with non-clotting blood. Hemorrhagic corpus luteal cyst was the
      initial impression. Ruptured appendicitis with abscess formation and complicated
      hemoperitoneum was diagnosed later with the aid of abdominal computed tomographic
      scan, and was confirmed during operation. Hemoperitoneum may be a complication of
      appendicitis with abscess formation; a detailed medical history and physical
      examination are helpful in making the diagnosis.

PMID- 14976572
TI  - Primary volvulus of the ileum in a preterm infant.
AB  - Primary volvulus of the small intestine is rare in neonates. We report a case of
      primary volvulus of the ileum in a preterm newborn. Vomiting and abdominal
      distension began 10 hours after birth, followed by hypovolemia, hyponatremia, and
      acidosis. Plain abdominal radiograph revealed a pattern of diffuse ileus and very
      dilated loops at the right upper quadrant of the abdomen. Three days later,
      another plain film showed increased fluid accumulation and decreased air in these
      dilated loops. Emergency laparotomy revealed primary volvulus of the distal ileum
      with gangrenous change. Resection of the necrotic ileum with an end-to-end
      ileoileostomy was performed and the patient recovered fully. In a newborn with
      ileus and rapidly deteriorating hemodynamics, early surgical intervention is
      essential to achieve good prognosis.

PMID- 14976573
TI  - Charting the course.

PMID- 14976574
TI  - Hermann Boerhaave (1668-1738): 18th century teacher extraordinaire.

PMID- 14976575
TI  - Recurrent appendicitis as a cause of recurrent right iliac fossa pain.
AB  - Recurrent appendicitis is defined when patients with recurring similar right
      iliac fossa pain had acute appendicitis confirmed at the time of operation and
      the pain completely subsided after surgery. We conducted a retrospective study on
      our patients with appendicitis. There were 290 patients with appendicitis over a
      two-year period and 33 patients (11%) had reported recurring pain prior to the
      presentation. Majority had one prior episode but 15% had multiple episodes of
      right iliac fossa pain. Fifty-eight percent of the episode occur within six
      months of the presentation. We conclude that recurrent appendicitis should be
      considered as a differential diagnosis in patients with recurrent right iliac
      fossa pain.

PMID- 14976576
TI  - Monkey bars are for monkeys: a study on playground equipment related extremity
      fractures in Singapore.
AB  - Studies in Caucasian populations have shown that a significant percentage of
      childhood extremity fractures occur at the playground. There are no comparable
      studies in Asian populations. Thus this study sets out to determine the pattern
      of playground related extremity fractures in Asian populations and to suggest
      modifications to prevent or reduce these injuries. This study involved a
      retrospective review of 390 patients with these fractures who visited our
      Department from May 1997 to December 1998. This accounted for 19.5% of all
      fractures seen in the same period. The largest age group affected were the five
      through 12-year-old patients with a male to female ratio of 2:1. Monkey bars or
      upper body devices were the most common cause (66%). The most common fracture was
      supracondylar fractures (43%). Further studies to determine the actual dimensions
      of playground equipment will be carried to ascertain with greater certainty the
      safety of these equipment in our playgrounds.

PMID- 14976577
TI  - Outcome of longstanding dislocated elbows treated by open reduction and excision
      of collateral ligaments.
AB  - AIM: To study the long term result of open reduction of longstanding dislocated
      elbows with regard to stability, avascular necrosis of the distal humerus and
      degenerative changes of the joint. METHODS: Nine patients, aged between nine and
      60 years (average 30 years) with longstanding posterior dislocation of the elbow
      underwent open reduction. The operative procedure featured a medial and lateral
      incision, excision of the capsule, fibrous adhesions and the collateral ligaments
      with no attempt to reconstruct the ligaments, as well as anterior transposition
      of the ulnar nerve. The procedure was performed on an average eight months after
      the injury (range 1.5 to 30 months). RESULTS: All elbows had improved flexion at
      follow-up which ranged from one to eleven-and-half years (average 48 months). The
      average arc of flexion improved from 11 degrees to 87 degrees. The average
      flexion at the elbow improved from 32 degrees (range 20 degrees - 50 degrees ) to
      111 degrees (range 85 degrees - 140 degrees ). Younger patients with fractures of
      the articular surface of distal humerus had smaller gain in the range of motion.
      No patient complained of instability or had recurrence of dislocation. No patient
      developed avascular necrosis of the distal end of the humerus. The radiographs of
      the 60-year-old man at 11.5 years follow-up showed extensive degenerative changes
      of the joint but he still maintained a painless arc of flexion from 10 degrees to
      135 degrees. CONCLUSION: There was improvement in the range of motion and
      function in all nine patients. The elbows were stable despite excision of the
      collateral ligaments. There was no evidence of avascular necrosis. Patients with
      eight or more years of follow-up showed degenerative changes of the joint.

PMID- 14976578
TI  - Prevalence, awareness, treatment and control of hypertension in the Malaysian
      adult population: results from the national health and morbidity survey 1996.
AB  - We determined the prevalence of hypertension and the level of awareness,
      treatment and control of hypertension among Malaysian adults in a population
      based cross-sectional survey. Twenty-one thousand and three hundred ninety-one
      adults aged 30 or older in all 13 states of Malaysia in 1996 were sampled using a
      stratified two-stage cluster sampling design. Thirty-three percent of adults had
      hypertension with a higher percentage among women. Among hypertensives, 33% were
      aware of their hypertension, 23% were currently on treatment and a mere 6% had
      controlled hypertension. There was practically no difference in mean BP between
      treated and untreated hypertensives. Concerted public health effort is urgently
      required to improve the detection, treatment and control of hypertension in
      Malaysia.

PMID- 14976579
TI  - A retrospective study of malaria infections in an intensive care unit of a
      general hospital in Malaysia.
AB  - AIMS: To study the clinical and demographic aspects as well as the outcomes of
      severe cases of malaria infections managed in the intensive care unit of the
      Sarawak General Hospital, Kuching from January 1996 to December 2001. METHODS:
      All cases of malaria admitted to the intensive care unit of the Sarawak General
      Hospital from January 1996 to December 2001 were identified from the intensive
      care records and retrospectively reviewed. RESULTS: A total of 31 cases of
      malaria were managed in the intensive care unit of the Sarawak General Hospital
      in the six-year period. Twenty-eight cases were P. falciparum infections; two
      were P. vivax and one was a mixed infection of P. falciparum and P. vivax. Fever
      with or without chills and rigors, headache, abdominal pain and vomiting were the
      four commonest presenting complaints for P. falciparum infections. Patients with
      both abdominal pain and hepatomegaly have significantly higher mortality. The
      fatal cases, at presentation, had higher parasite counts, higher bilirubin,
      aminotransferase, potassium and urea levels, but lower haemoglobin and platelet
      counts, and more deranged coagulation profiles compared to surviving patients.
      The major complications include acute renal failure, acute respiratory distress
      syndrome, cerebral malaria and disseminated intravascular coagulopathy,
      haemolytic anaemia and liver dysfunction. A single case of vivax malaria, which
      was complicated by septicaemic shock and disseminated intravascular coagulopathy
      was also documented. Higher mortality rate was documented if the antimalarial
      medication was not commenced on the day of admission into hospital. CONCLUSION:
      Several infections of P. falciparum are still associated with significant
      mortality. Other confounding factors include the patient's own initiating quinine
      therapy. Aggressive and appropriate therapy is life saving. Earlier anti-malaria
      treatment may improve the survival rate for falciparum malaria. The isolated case
      of death from P. vivax infection argues against complacency in the management of
      even the "benign" form of the infection.

PMID- 14976580
TI  - The superior gluteal artery perforator flap for the closure of sacral sores.
AB  - The purpose of this paper is to report the use of the superior gluteal artery
      perforator (SGAP) flap in the closure of sacral pressure sores here in Singapore.
      This fasciocutaneous flap is a refinement of the musculocutaneous flap which is
      popularly used for the closure of sacral sores. There were minimal complications.
      This is a reliable flap and gives the option of further reconstructive
      possibilities should a recurrence occur.

PMID- 14976581
TI  - Temporal lobe encephalocoele presenting with seizures and hearing loss.
AB  - A case of a bilateral temporal lobe encephalocoele that presented as seizures and
      hearing loss for many years. Diagnosis was confirmed on CT and MR imaging, which
      showed deficiencies in the temporal bone. The patient subsequently underwent
      surgical repair and recovered from his presenting symptoms.

PMID- 14976582
TI  - Clinics in diagnostic imaging (93).
AB  - A 63-year-old woman was found to have pathological fracture of the right lower
      tibia through a brown tumour, hypercalcemia, and a soft tissue mass at the lower
      pole of the right lobe of thyroid gland. US scan of the neck showed a well
      circumscribed heterogeneously-hypoechoic mass with displacement of the right lobe
      of thyroid gland. Diagnosis of parathyroid adenoma was confirmed on
      histopathological examination of the excised specimen. The cause and clinical
      manifestations of primary hyperparathyroidism are discussed. Imaging methods of
      parathyroid gland are presented.

PMID- 14976583
TI  - Smoke induced changes in epithelial cell gene expression: development of an in
      vitro model for COPD.
AB  - Chronic obstructive pulmonary disease (COPD) includes emphysema and chronic
      bronchitis, which are characterised by a progressive airflow limitation and
      chronic inflammation. The pathogenesis of COPD involves different cells, mainly
      epithelial cells, macrophages, neutrophils, and CD8 lymphocytes. Bronchial
      epithelium lines the mucosal surface of the airways, forming a mechanical barrier
      that separates the external environment from the internal milieu. Recently,
      substantial evidence has emerged indicating that airway epithelial cells are able
      to liberate a number of chemokines fundamental to both inflammatory and immune
      responses. Therefore, we established an in vitro model by showing that cigarette
      smoke is able to induce the release of chemokines by lung epithelial cells.
      Furthermore, we show that cigarette smoke induced chemokine expression is
      resistant to dexamethasone, mimicking the clinical situation. In contrast,
      pyrrolidinedithiocarbamic acid, an experimental antioxidant compound, inhibited
      smoke induced chemokine expression. These results suggest that this epithelial
      cell culture model may allow the evaluation of novel anti-inflammatory compounds
      for the treatment of COPD directly on the relevant target cells in vitro. This
      approach may result in the replacement of animal experimentation in screening of
      new therapeutics for COPD.

PMID- 14976584
TI  - Avoidance of animal experiments in the new EU Chemicals Regulation -
      opportunities and problems from the point of view of animal welfare.
AB  - On 29 October 2003, the European Commission forwarded the "Proposal for a
      Regulation of the European Parliament and of the Council concerning the
      Registration, Evaluation, Authorization and Restriction of Chemicals (REACH),
      establishing a European Chemicals Agency and amending Directive 1999/45/EC and
      Regulation (EC) on Persistent Organic Pollutants" to the European Parliament and
      the Council for adoption under the so-called co-decision procedure. From the
      point of view of animal welfare it is to be welcomed that it is envisaged better
      to protect humans and the environment from unknown risks through chemical
      substances. However, in order to ensure that this goal can be met, extensive
      amendments to the proposed draft are requested: Instead of continuing to perform
      animal tests, relevant and reliable non-animal testing strategies should be
      implemented. Before considering testing, all existing data must be made
      available, shared and evaluated. This request should be enforced in the new
      Regulation through an adequate mandatory system. Data requirements must be
      tailored to the specific substance, to ensure that only such information is
      collected that is necessary for its safe handling by workers and consumers.
      Missing data should be determined with non-animal test methods. Finally, the
      European Union and its Member States are called to provide adequate funding for
      alternative method research without delay and to call for tenders on those
      information-gaps that currently prevent the implementation of an entirely non
      animal testing strategy, so that such new methods will be available in time for
      application under the REACH system.

PMID- 14976585
TI  - Trends in improving the embryonic stem cell test (EST): an overview.
AB  - The embryonic stem cell test (EST) is an in vitro assay that has been developed
      to assess the teratogenic and embryotoxic potential of drugs and chemicals. It is
      based on the capacity of murine ES cells (cell line D3) to differentiate into
      contracting myocardial cells under specific cell culture conditions. The
      appearance of beating cardiomyocytes in embryoid body (EB) outgrowths is used as
      a toxicological endpoint to assess the embryotoxic potential of a test substance.
      Applying linear analysis of discriminance, a biostatistical prediction model (PM)
      was developed to assign test chemicals to three classes of embryotoxicity. In an
      international validation study the EST predicted the embryotoxic potential of
      chemicals and drugs with the same reliability as two other in vitro
      embryotoxicity tests, which employed embryonic cells and tissues from pregnant
      animals. In a joint research project with German pharmaceutical companies we have
      successfully improved the EST by establishing molecular endpoints of
      differentiation in cultured ES cells. The quantification of cardiac-specific
      protein expression by intracellular flow cytometry has been studied in the
      presence of chemicals of different embryotoxic potential. The results obtained
      using molecular endpoints specific for differentiated cardiomyocytes employing
      FACS (fluorescence-activated cell sorting) analysis will be presented in
      comparison to the validated endpoint - the microscopic analysis of beating areas.
      FACS analysis provides a more objective endpoint for predicting the embryotoxic
      potential of chemicals than the validated method. Furthermore, flow cytometry
      promises to be suitable for high-throughput screening systems (HTS). In addition,
      our partners from the joint project have improved the EST by developing protocols
      that stimulate differentiation of ES cells into neural and endothelial cells,
      chondrocytes and osteoblasts, because some substances might have embryotoxic
      effects on specific cell-types other than cardiomyocytes. These protocols have
      been successfully established at ZEBET and in the participating laboratories.
      Additionally, molecular endpoints have been established for the detection of
      specific differentiation pathways. Furthermore, new prediction models (PMs) have
      been developed using single endpoints of the EST.

PMID- 14976586
TI  - [About animal experiments for a face without wrinkles].
AB  - Botulinum toxin, a nervous poison produced by bacteria, is increasingly being
      used - besides its medical application - as a beauty product for smoothing facial
      wrinkles. It is unknown in public that each batch of the toxin has to undergo a
      quality control before marketing. The test used is a LD50 test using mice that is
      very animal consuming and causes extreme suffering. Although several alternative
      methods exist, none of these are have yet been adopted by the European
      pharmacopoeia. Consumers in the EU do not accept animal experiments for cosmetic
      purposes. However, Botulinum toxin does not fall under the definition of a
      "cosmetic product" and therefore the bans on animal experiments laid down in the
      EU Cosmetic Directive do not apply. Therefore on a short term scale, only the
      voluntarily renouncement of the use of this toxin as an anti-wrinkling agent can
      prevent the suffering and death of animals for a beauty product.

PMID- 14976587
TI  - Age-dependent changes of gap detection in the Mongolian gerbil (Meriones
      unguiculatus).
AB  - Gap detection using broadband noise was characterized in a group of young gerbils
      from the breeding colony of the University of Regensburg (RB gerbils), old RB
      gerbils, and old gerbils from the breeding colony of the University of South
      Carolina (SC gerbils). Data from old RB and old SC gerbils were not significantly
      different and were subsequently combined for a comparison with data from the
      group of young RB gerbils. Level dependence of gap-detection thresholds in young
      and old domesticated gerbils resembled the typical mammalian pattern of level
      dependence. Gap-detection thresholds of old gerbils were significantly elevated
      at 30 dB SL and 50 dB SPL as compared with young gerbils. Compared with young
      gerbils tested at 30 dB SL and 50 dB SPL, the distribution of gap-detection
      thresholds in old gerbils was broader with a spread to higher gap-detection
      thresholds. Some old animals retained excellent temporal resolution, while some
      showed impaired gap detection. The gap-detection data collected in young and old
      gerbils resemble previously published data from humans of different age and
      confirm that gerbils are a useful model to study age-dependent changes in
      temporal processing.

PMID- 14976588
TI  - Purinergic modulation of cochlear partition resistance and its effect on the
      endocochlear potential in the Guinea pig.
AB  - Introduction of adenosine 5'-triphosphate (ATP) into the endolymphatic
      compartment of the guinea-pig cochlea decreases the endocochlear potential (EP).
      To determine if this is due to an ATP-induced change in compartment resistance,
      the cochlear partition resistance (CoPR) was measured using constant current
      injections into scala media before, during, and after microinjection of ATP into
      the same compartment. The CoPR (mean = 3.13 +/- 0.13 kOmega) decreased with ATP
      in a dose-dependent manner (25.1 +/- 3.0% decrease in relation to baseline
      values) and this was linearly correlated ( R(2) = 0.91) to the magnitude of the
      ATP-induced decline in EP (41.6 +/- 7.0% decline in relation to the baseline).
      Pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, a P2X receptor
      antagonist) injected prior to ATP application blocked this ATP-induced reduction
      in EP and CoPR. This indicates that ATP-gated ion channels (P2X receptors)
      provide a latent shunt capable of regulating the majority of the electrical
      potential across the luminal surface of the sensory hair cells, which is
      necessary for sound transduction. The results suggest a novel sound transduction
      regulatory mechanism, which, via extracellular ATP, has the capability of
      adjusting hearing sensitivity.

PMID- 14976589
TI  - Functional maturation of nicotinic acetylcholine receptors as an indicator of
      murine muscular differentiation in a new nerve-muscle co-culture system.
AB  - Under normal conditions in situ, muscle fibers and motoneurons, the main partners
      of motor units, are strongly dependent on each other. This interdependence
      hinders ex vivo studies of neuromuscular disorders where nervous or muscular
      components are considered separately. To allow in vitro access to complex nerve
      muscle relationships, we developed a novel nerve-muscle co-culture system where
      mouse muscle innervation is assured by rat spinal cord explants. The degree of
      muscular maturation during co-culture was evaluated using the distribution of
      nicotinic acetylcholine receptors (AChRs) and their electrophysiological
      characteristics before and after innervation. In myotubes from non-innervated
      cultures, AChRs were diffusely distributed over the entire myotube surface. Their
      single-channel conductance (33.5+/-0.6 pS) and mean open time (8.1+/-0.7 ms) are
      characteristic of AChRs described in embryonic or denervated skeletal muscles. In
      innervated muscle fibers from co-cultures, AChRs appear as discrete aggregates
      and co-localize with synaptotagmin. In addition to the embryonic type currents,
      in innervated fibers AChR currents having high conductance (53.3+/-5.9 pS) and
      short mean open time (2.6+/-0.1 ms), characteristic of AChRs at mature
      neuromuscular junctions, were observed. Our data support the use of this new
      nerve-muscle co-culture system as a reliable model for the study of murine
      muscular differentiation and function.

PMID- 14976590
TI  - Salad and pseudoappendicitis: Yersinia pseudotuberculosis as a foodborne
      pathogen.

PMID- 14976591
TI  - Ethical conduct of research in resource-limited settings.

PMID- 14976592
TI  - A widespread outbreak of Yersinia pseudotuberculosis O:3 infection from iceberg
      lettuce.
AB  - BACKGROUND: The vehicles and sources of Yersinia pseudotuberculosis infection are
      unknown. In Finland, clinical microbiology laboratories routinely report Y.
      pseudotuberculosis isolations and submit isolates for serotype analysis. In
      October 1998, the number of serotype O:3 infections increased markedly. METHODS:
      Case patients with culture-confirmed Y. pseudotuberculosis O:3 infection were
      identified by use of laboratory-based surveillance. We conducted a population
      based case-control study. Healthy community control subjects were matched by age,
      sex, and postal code. Isolates were subtyped by pulsed-field gel electrophoresis
      (PFGE). RESULTS: Nationwide, 47 case patients were identified (age range, 2-77
      years; median, 19 years). One patient with bacteremia died; 5 underwent
      appendectomies. We enrolled 38 case patients and 76 control subjects in the case
      control study. Seventy-one percent of case patients and 42% of control subjects
      reported having eaten iceberg lettuce (matched odds ratio, 3.8; 95% confidence
      interval, 1.3-9.4); a dose-response relationship was found for increasing
      frequency of consumption. Of the 27 isolates obtained from case patients and
      tested in the analysis, all had indistinguishable PFGE patterns. Four lunch
      cafeterias that had served iceberg lettuce were associated with clusters of case
      patients. The lettuce was traced back to originating farms. CONCLUSIONS: Iceberg
      lettuce was implicated as the vehicle of a widespread foodborne Y.
      pseudotuberculosis outbreak. Ongoing laboratory-based surveillance and serotype
      analysis were essential in the rapid detection of infection. Cases of
      yersiniosis, which appear to be sporadic, may be part of unrecognized outbreaks
      caused by contaminated fresh produce.

PMID- 14976593
TI  - Does the presence of pneumococcal DNA in middle-ear fluid indicate pneumococcal
      etiology in acute otitis media?
AB  - Bacterial culture of middle-ear fluid (MEF), the standard for etiologic diagnosis
      of acute otitis media (AOM), has revealed Streptococcus pneumoniae (Pnc) to be a
      major pathogen responsible for one-third of AOM cases. In the present study, we
      compared the results of polymerase chain reaction (PCR) based on the
      amplification of the pneumolysin gene with the results of pneumococcal culture,
      for 2595 MEF samples obtained during AOM events in 831 children who were followed
      from 2-24 months of age in the Finnish Otitis Media Vaccine Trial. PCR results
      were positive for 47.1% of the MEF samples, and culture results were positive for
      27.3% of the samples. PCR-positive, culture-negative samples were associated with
      previous Pnc AOM in a time-dependent pattern, concurrent antibiotic treatment,
      low volume of MEF, and concurrent nasopharyngeal carriage. PCR-positive AOM
      represented a clinically less severe disease, compared with culture-positive Pnc
      AOM. A positive PCR result seemed to indicate the presence of viable, although
      often nonculturable, Pnc.

PMID- 14976594
TI  - Effect of clonal and serotype-specific properties on the invasive capacity of
      Streptococcus pneumoniae.
AB  - The present study compares the molecular epidemiology of Streptococcus pneumoniae
      causing invasive disease and carriage, respectively, in one geographic area
      (Stockholm, Sweden) during a specific point in time (the year 1997). A total of
      273 invasive isolates (257 from adults and 16 from children) obtained from the 2
      major hospitals in Stockholm, as well as 246 nasopharyngeal isolates recovered
      from children attending 16 day-care centers in the Stockholm area, were analyzed
      by serotyping, molecular typing (by pulsed-field gel electrophoresis and
      multilocus sequence typing), and antibiotic susceptibility testing. Of the 34
      different serotypes plus nontypeable strains identified in the present study, 12
      were never found among the 246 colonizing isolates, whereas only 3 were never
      found among the 273 invasive isolates. The isolates formed 2 major classes: 1
      class that was found mainly among invasive isolates (type 1, 4, 7F, and 9V
      isolates) and was clonally highly related and 1 class that caused invasive
      disease but was also common in carriage (including type 6A, 6B, 14, and 19F
      isolates) and was genetically more diverse. Clones were found that belonged to
      the same serotype but had different abilities to cause invasive disease. Also,
      isolates belonging to the same clone were found, although they had different
      capsules because of serotype switch, and were found to have the same disease
      potential. Hence, properties associated with a particular clonal type, in
      addition to capsular serotype, are likely to be important for the potential of
      pneumococci to cause invasive disease.

PMID- 14976595
TI  - Low antibody levels against cell wall-attached proteins of Streptococcus pyogenes
      predispose for severe invasive disease.
AB  - Acute-phase serum samples from 70 patients with group A streptococcal (GAS)
      invasive disease were analyzed for IgG antibodies against 6 recently
      characterized GAS virulence factors (SclA, SclB, GRAB, MtsA, EndoS, and IdeS) and
      SpeB. Antibody levels against the cell wall-attached GAS antigens SclA, SclB, and
      GRAB were significantly lower in patients with severe invasive disease
      (streptococcal toxic shock syndrome [STSS] and/or necrotizing fasciitis [NF];
      n=35), compared with levels in patients with nonsevere GAS bacteremia (n=35).
      Among patients with severe invasive disease, significantly lower antibody levels
      against GRAB were found in patients with STSS (n=10) than in patients with NF
      (n=17). Antibody levels against SpeB in patients with severe bacteremia were
      similar to those in patients with nonsevere bacteremia, and levels in patients
      with STSS were similar to those in patients with NF. The data indicate that
      immunity to cell wall-attached proteins may play a role in the protection against
      severe invasive disease and that antibodies against GRAB may be of importance in
      the pathogenesis of STSS.

PMID- 14976596
TI  - Human leukocyte antigen class I supertypes influence susceptibility and severity
      of tuberculosis.
AB  - Although both differential susceptibility to Mycobacterium tuberculosis infection
      and disease pathogenesis depend on a multitude of factors, elucidation of
      specific host genetic markers, particularly those in the human major
      histocompatibility complex, is important. The present study is an attempt to
      delineate human leukocyte antigen (HLA) class I association in tuberculosis (TB)
      on the basis of a shared sequence motif in peptide-binding pockets of HLA
      molecules. In patients with pulmonary TB and miliary/disseminated TB, we observed
      significantly increased frequencies of A3-like supertypes and decreased
      frequencies of A1-like supertypes. These 2 positively and negatively associated
      supertypes (allele groups) share a similar peptide-binding motif, except for
      residues in pocket F of the HLA class I molecules. In addition, the HLA-Cw
      specificities that are major ligands for killer cell immunoglobulin-like
      (inhibitory) receptors (KIRs), particularly KIR2DL1 (Cw2, Cw4, and CW5) and
      KIR2DL2 (Cw1, Cw3, and Cw7), were found more frequently among patients with TB,
      which suggests a possible inhibition of natural killer cell activity against the
      infected target cells. The results of the present study suggest that the frequent
      occurrence of HLA class I specificities comprising an A3-like peptide-binding
      motif and the increased occurrence of ligands for KIR2DL in TB together may
      influence the outcome of TB.

PMID- 14976597
TI  - Mapping immune reactivity toward Rv2653 and Rv2654: two novel low-molecular-mass
      antigens found specifically in the Mycobacterium tuberculosis complex.
AB  - New tools are urgently needed for the detection of latent tuberculosis (TB). We
      evaluated the diagnostic potential of 2 novel Mycobacterium tuberculosis complex
      specific candidate antigens (Rv2653 and Rv2654) and investigated T cell
      recognition during natural infection in humans and experimental infection in
      guinea pigs. Peripheral blood mononuclear cells stimulated with peptide pools
      covering the full length of Rv2654 induced interferon- gamma release in 10 of 19
      patients with TB. Neither Rv2654 single peptides nor Rv2654 pools were recognized
      by bacille Calmette-Guerin-vaccinated donors. However, peptides from Rv2653 were
      recognized by both patients group. The cross-reactive epitope(s) in Rv2653 were
      located in a 36-amino acid stretch in the center of the molecule. Rv2654 also
      induced M. tuberculosis-specific skin-test responses in 3 of 4 aerosol-infected
      guinea pigs. Rv2654 is a strongly recognized T cell antigen that is highly
      specific for TB and has potential as a novel cell-mediated immunity-based TB
      diagnostic agent.

PMID- 14976598
TI  - Association between diversity in the Src homology 2 domain--containing tyrosine
      phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy
      and cancer.
AB  - We investigated the relationship between the diversity of Helicobacter pylori
      CagA protein and clinical outcome. The cagA gene was sequenced in 115 clinical
      isolates. The binding affinity of CagA to Src homology 2 domain-containing
      tyrosine phosphatase (SHP-2) was examined by in vitro infection. Two major CagA
      subtypes were observed--the East Asian and the Western type. The grades of
      inflammation, activity of gastritis, and atrophy were significantly higher in
      patients with gastritis infected with the East Asian CagA-positive strain than in
      patients with gastritis infected with cagA-negative or Western CagA-positive
      strains. All strains isolated from patients with gastric cancer were East Asian
      CagA positive. East Asian CagA exhibited stronger SHP-2-binding activity than did
      Western CagA. These findings suggest that infection with East Asian CagA-positive
      H. pylori is associated with atrophic gastritis and gastric cancer and that
      persistent active inflammation induced by the East Asian CagA-positive strain may
      play a role in the pathogenesis of disease.

PMID- 14976599
TI  - Modulation of immune response to group C meningococcal conjugate vaccine given
      intranasally to mice together with the LTK63 mucosal adjuvant and the trimethyl
      chitosan delivery system.
AB  - Previous work had shown that the immunogenicity of conjugate vaccine against
      group C meningococci (CRM-MenC) is enhanced when it is delivered intranasally
      (inl) with mucosal adjuvants, such as mutants of the Escherichia coli enterotoxin
      (LT), and with delivery systems such as chitosan derivatives. We show, in mice,
      that the concomitant use of limiting doses of the fully nontoxic LTK63 mutant as
      a mucosal adjuvant and of the trimethyl derivative of chitosan as a delivery
      system allows the reduction of each of the components for the induction of
      antibody and bactericidal responses to CRM-MenC conjugate vaccine delivered inl
      at titers similar to or higher than those induced by parenteral immunization.
      These data could affect the design of efficacious mucosal vaccines and their
      safety.

PMID- 14976600
TI  - Toll-like receptor 4 is critical to innate host defense in a murine model of
      bordetellosis.
AB  - Bordetellae are important respiratory pathogens that cause pertussis (whooping
      cough) in humans and analogous diseases in domestic and wild animals. Immunity to
      Bordetella is poorly understood, in particular the early innate immune responses
      that contribute to inflammation, pathology, and the subsequent generation of
      adaptive immunity. Using B. bronchiseptica, which naturally infects mice, we show
      that Toll-like receptor-4 (TLR4) is required for cytokine responses to this
      pathogen's lipopolysaccharide (LPS) and that TLR4 deficiency results in impaired
      cytokine responses in vitro and in vivo. TLR4-deficient mice rapidly succumb
      following inoculation with as few as 1000 organisms, indicating that TLR4 is
      critical to innate host defense against bordetellosis.

PMID- 14976601
TI  - Genotypic and phenotypic predictors of the magnitude of response to tenofovir
      disoproxil fumarate treatment in antiretroviral-experienced patients.
AB  - Results from 2 placebo-controlled intensification trials of tenofovir disoproxil
      fumarate (DF) in treatment-experienced human immunodeficiency type 1 (HIV-1)
      infected patients (n=332) were integrated to determine the effects of resistance
      at baseline on HIV-1 RNA response. In these trials, there was a high prevalence
      of HIV-1 resistance mutations, with 94% of patients having nucleoside-associated
      mutations and 71% having thymidine analogue-associated mutations (TAMs).
      Statistically significant HIV-1 RNA reductions associated with tenofovir DF
      treatment, relative to placebo (P<.001), were observed for patients without TAMs
      (n=97) or for patients with 1-2 (n=88) or >or=3 TAMs (n=147). Response to
      tenofovir DF was reduced among patients with HIV-1 with >or=3 TAMs inclusive of
      either the M41L or L210W mutation (n=86) or patients who had a preexisting K65R
      mutation (n=6). Slightly increased treatment responses were observed when the
      M184V mutation was present. Phenotypic cutoffs were established at 1.4-fold and 4
      fold, respectively, for the beginning of reduced response to tenofovir DF and for
      a strongly reduced response. The results from these controlled clinical trials
      provide guidance for the use of tenofovir DF for treatment-experienced patients.

PMID- 14976602
TI  - Persistent parvovirus B19 infection without the development of chronic anemia in
      HIV-infected and -uninfected children: the Women and Infants Transmission Study.
AB  - We evaluated the prevalence of persistent parvovirus B19 (B19) infection and
      associated anemia in human immunodeficiency virus (HIV)-infected and HIV
      uninfected children. B19 persistence was defined as B19 DNA detected in specimens
      collected >16 weeks apart. Of 182 children, 3 HIV-infected children and two HIV
      uninfected children had evidence of persistent B19 infection. Of the 5 children,
      none had evidence of B19-associated anemia. Our data suggest that B19 infections
      can persist in children without the development of symptomatic anemia.

PMID- 14976603
TI  - HIV-1-infected patients with envelope-specific lymphoproliferation or long-term
      nonprogression lack antibodies suppressing glycoprotein 120 antigen presentation.
AB  - BACKGROUND: Antibodies to the CD4-binding domain (CD4bd) of human
      immunodeficiency virus type 1 (HIV-1) glycoprotein 120 (gp120) inhibit gp120
      antigen presentation to CD4 T cells. These findings imply that the presence of
      anti-CD4bd antibodies might contribute to the dearth of envelope-specific T
      helper responses observed in most HIV-1-positive patients. In the absence of
      these antibodies, however, anti-envelope T helper responses might be maintained.
      METHODS: We used ELISA to evaluate the levels of anti-CD4bd antibodies in rare
      HIV-1-positive patients who exhibit envelope-specific lymphoproliferation.
      Subsequently, we examined the contribution of anti-CD4bd antibodies to disease
      progression by comparing anti-CD4bd antibody levels in 3 cohorts of HIV-1
      positive patients with distinct rates of disease progression. RESULTS: Although
      most HIV-1-positive individuals produce anti-CD4bd antibodies, 77% of patients
      with envelope-specific lymphoproliferation have undetectable anti-CD4bd antibody
      levels. Moreover, comparison of the 3 HIV-1-positive cohorts revealed that
      individuals with long-term nonprogression have significantly lower anti-CD4bd
      antibody titers than do those with rapid or slow progression. Unlike
      immunoglobulin G (IgG) from rapid progressors, IgG from nonprogressors had no
      suppressive effects on glycoprotein (gp) 120-specific T cell proliferation.
      CONCLUSIONS: Low anti-CD4bd antibody levels are associated with the absence of
      disease progression. A number of HIV-1-positive individuals without these
      antibodies also appear to sustain gp120-specific T helper responses needed to
      help control the infection.

PMID- 14976604
TI  - A survival method to estimate the time to occurrence of mutations: an application
      to thymidine analogue mutations in HIV-1-infected patients.
AB  - Virologic studies of human immunodeficiency virus type 1-infected patients have
      investigated either the emergence of resistance mutations according to the
      treatment received (type I) or their effect on subsequent regimens (type II).
      Type I studies provide an estimation of the frequency distribution of mutations
      for a given duration of therapy, but the delay to emergence of these mutations
      cannot be assessed. We suggest using a nonparametric estimator that generalizes
      the Kaplan-Meier method to data from type II studies to estimate the time to
      occurrence of mutations. Patients had no treatment interruption before viral
      genotyping. Although the curves should be interpreted with caution, they provide
      useful information about the kinetics of the emergence of mutations. The method
      was applied to the emergence of thymidine analogue mutations in patients
      previously treated with zidovudine (ZDV) plus didanosine or zalcitabine. Although
      K70R has been described as the first mutation to appear in patients receiving ZDV
      monotherapy, the T215Y/F mutation appeared first in patients receiving dual
      nucleoside combination therapy.

PMID- 14976605
TI  - Polymorphism of transporter associated with antigen presentation 1 as a potential
      determinant for severity of disease in recurrent respiratory papillomatosis
      caused by human papillomavirus types 6 and 11.
AB  - Recurrent respiratory papillomatosis (RRP) is a rare disease caused by human
      papillomaviruses (HPVs). It is characterized by multiple recurrences of benign
      neoplasms and has a variable clinical course, ranging from infrequent recurrence
      to acute airway obstruction. One way in which HPV subverts the immune system in
      RRP is by interfering with TAP1 (transporter associated with antigen presentation
      1). We examined whether a known TAP1 polymorphism in the ATPase domain altered
      the severity of disease in patients with RRP. The presence of this polymorphism
      was significantly correlated with severity of disease (P=.015). Because of the
      proximity of the TAP1 gene to human leukocyte antigen (HLA) class II genes on
      chromosome 6, we postulated that a linkage disequilibrium may exist. Of the
      patients with polymorphic TAP1, 36% were positive for HLA-DRB1*0102 (P=.021;
      P=.147 with Bonferroni's correction). However, this association appeared to
      mitigate the severity of disease (P=.04). Therefore, severity of disease in a
      patient with RRP might be determined by sequencing TAP1, in conjunction with HLA
      class II genes.

PMID- 14976606
TI  - Impaired T helper 1 function of nonstructural protein 3-specific T cells in
      Japanese patients with encephalitis with neurological sequelae.
AB  - Japanese encephalitis virus (JEV) is the principal cause of viral encephalitis.
      The predominance of children among patients with encephalitis in areas where JEV
      is endemic that do not have immunization programs suggests that acquired immunity
      is critical in protecting adults against symptomatic JEV encephalitis. We
      characterized and compared the T cell response to nonstructural (NS) protein 3
      between healthy individuals naturally exposed to JEV and patients in the
      convalescent phase of JEV encephalitis. The NS3 protein, used as a fusion to the
      11-amino acid protein transduction domain of human immunodeficiency virus Tat,
      elicited CD4(+) and T helper-dependent CD8(+) T cell responses. The production of
      interferon (IFN)- gamma by responding T cells was significantly higher in healthy
      donors than in patients, correlating strongly with acquired protective immunity
      to JEV. Furthermore, a striking inverse association between IFN- gamma levels and
      the severity of postencephalitic sequelae in patients implicated a role of IFN-
      gamma in recovery.

PMID- 14976607
TI  - Long-term treatment of intestinal helminths increases mite skin-test reactivity
      in Gabonese schoolchildren.
AB  - BACKGROUND: Several studies have shown an inverse association between helminth
      infections and atopy, but none have clearly established that the pathogens
      themselves, rather than other associated factors, cause the suppression of atopy.
      To show a direct link, prospective intervention studies are required. METHODS: A
      randomized, controlled trial was performed to study whether repeated
      anthelminthic treatment results in increased allergic sensitivity to house dust
      mites (HDMs) in chronically infected children. The trial population consisted of
      317 Gabonese schoolchildren with a high prevalence of intestinal helminths.
      Intervention consisted of treatment every 3 months with praziquantel and
      mebendazole and with placebo in the control group. Follow-up lasted 30 months: at
      6-month intervals, skin-test sensitivity to mites, helminth infection status, and
      levels of total IgE were determined. RESULTS: Treatment resulted in a significant
      increase in the rate of developing skin sensitivity to HDMs (hazard ratio, 2.51;
      95% confidence interval, 1.85-3.41), which was mediated, in part, by reductions
      in Ascaris and/or Trichuris infections. Levels of total IgE were reduced, but
      this did not mediate the effect of treatment on skin-test reactivity.
      CONCLUSIONS: Anthelminthic treatment of chronically infected children results in
      increased atopic reactivity, which indicates that helminths directly suppress
      allergic reactions.

PMID- 14976608
TI  - Fosmidomycin-clindamycin for Plasmodium falciparum Infections in African
      children.
AB  - BACKGROUND: Fosmidomycin is a new antimalarial drug with a novel mechanism of
      action. Studies in Africa that have evaluated fosmidomycin as monotherapeutic
      agent demonstrated its excellent tolerance, but 3-times-daily treatment regimens
      of >or=4 days were required to achieve radical cure, prompting further research
      to identify and validate a suitable combination partner to enhance its efficacy.
      METHODS: We conducted a randomized, controlled, open-label study to evaluate the
      efficacy and safety of fosmidomycin combined with clindamycin (n=12; 30 and 5
      mg/kg body weight every 12 h for 5 days, respectively), compared with
      fosmidomycin alone (n=12; 30 mg/kg body weight every 12 h for 5 days) and
      clindamycin alone (n=12; 5 mg/kg body weight every 12 h for 5 days) for the
      clearance of asymptomatic Plasmodium falciparum infections in schoolchildren in
      Gabon aged 7-14 years. RESULTS: Asexual parasites were rapidly cleared in
      children treated with fosmidomycin-clindamycin (median time, 18 h) and
      fosmidomycin alone (25 h) but slowly in children treated with clindamycin alone
      (71 h; P=.004). However, only treatment with fosmidomycin-clindamycin or
      clindamycin alone led to the radical elimination of asexual parasites as measured
      by day 14 and 28 cure rates of 100%. Asexual parasites reappeared by day 28 in 7
      children who received fosmidomycin (day 14 cure rate, 92% [11/12; day 28 cure
      rate, 42% [5/12]). All regimens were well tolerated, and no serious adverse
      events occurred. CONCLUSION: The combination of fosmidomycin and clindamycin is
      well tolerated and superior to either agent on its own with respect to the rapid
      and radical clearance of P. falciparum infections in African children.

PMID- 14976609
TI  - Frequency of interferon- gamma -producing T cells specific for Trypanosoma cruzi
      inversely correlates with disease severity in chronic human Chagas disease.
AB  - This study sought to quantify CD8(+) T cell responses to Trypanosoma cruzi and to
      identify potential links between these responses and the severity of disease in
      humans. In the majority of patients with Chagas disease, staining with class I
      major histocompatibility complex tetramers and analysis of interferon (IFN)-
      gamma ELISPOT responses to a panel of known cytotoxic T lymphocyte target
      epitopes from T. cruzi failed to identify parasite-specific CD8(+) T cells.
      However, the frequency of individuals with positive ELISPOT responses was higher
      in areas of active transmission. Analysis of IFN- gamma ELISPOT responses to a
      parasite lysate revealed a very high frequency of responders among patients with
      mild clinical disease and a very low frequency of responders among those with the
      most severe form of the disease. These data suggest that the frequency of IFN-
      gamma -producing T cells in patients with chronic Chagas disease is associated
      with the history of recent exposure and with the clinical status of the patient.

PMID- 14976611
TI  - What makes clinical research in developing countries ethical? The benchmarks of
      ethical research.

PMID- 14976610
TI  - Cloning, yeast expression, isolation, and vaccine testing of recombinant
      Ancylostoma-secreted protein (ASP)-1 and ASP-2 from Ancylostoma ceylanicum.
AB  - cDNAs encoding 2 Ancylostoma-secreted proteins (ASPs), Ancylostoma ceylanicum
      (Ay)-ASP-1 and Ay-ASP-2, were cloned from infective third-stage larvae (L3) of
      the hookworm A. ceylanicum and were expressed as soluble recombinant fusion
      proteins secreted by the yeast Pichia pastoris. The recombinant fusion proteins
      were purified, adjuvant formulated, and injected intramuscularly into hamsters.
      Hamsters vaccinated either by oral vaccination with irradiated L3 (irL3) or by
      injections of the adjuvants alone served as positive and negative controls,
      respectively. Anti-ASP-1 and anti-ASP-2 antibody titers exceeded 1 : 100000. Each
      vaccinated hamster was challenged orally with 100 L3. Two groups of vaccinated
      hamsters (i.e., those vaccinated with either irL3 or ASP-2 formulated with Quil
      A) exhibited significant reductions in adult hookworm burdens, compared with
      control hamsters. The hookworms recovered from the hamsters vaccinated with ASP-2
      plus Quil A were reduced in length. Splenomegaly, which was observed in control
      hamsters, was not seen in hamsters vaccinated with either irL3 or ASP-2
      formulated with Quil A. These results indicate that ASP-2 is a promising molecule
      for the development of a hookworm vaccine.

PMID- 14976612
TI  - Ricketts creates rickettsiology, the study of vector-borne obligately
      intracellular bacteria.

PMID- 14976613
TI  - Teaching our students as we want to be taught.

PMID- 14976614
TI  - Will the veterinary profession flourish in the future?

PMID- 14976615
TI  - Animal behaviour learning environment: software to facilitate learning in canine
      and feline behavior therapy.
AB  - Interactive software has been developed on CD-ROM to facilitate learning of
      problem formulation, diagnostic methodology, and therapeutic options in dog and
      cat behavior problems. Students working in small groups are presented with a
      signalment, a case history, and brief description of the problem behavior as
      perceived by the client. Students then navigate through the case history by
      asking the client questions from an icon-driven question pad. Animated video
      responses to the questions are provided. Students are then required to rate the
      significance of the questions and answers with respect to the development of the
      unwelcome behavior. Links to online self-assessments and to resource materials
      about causation and treatment options are provided to assist students in their
      decision-making process. The activity concludes with a software-generated e-mail
      submission that includes the recorded history, diagnosis, and recommended
      treatment for assessment purposes.

PMID- 14976616
TI  - New technology imperatives in medical education.
AB  - A great deal of effort has been expended on trying to determine whether
      traditional instruction, online learning, or some combination of the two is of
      greater educational effectiveness.1, 2 This may be the wrong question. Rather
      than determining whether one delivery mechanism is superior to another, it is
      more important to choose the best method(s) of delivery to achieve specific
      educational objectives, taking into consideration the different learning styles
      and circumstances of the target audience. Although appropriate use of technology
      offers potential for improved learning, there are other compelling reasons to use
      technology in medical education, such as reaching a different audience or
      accessing unique expertise that would otherwise be unavailable. This article
      explores the ramifications of three important drivers of technology adoption for
      medical education: (1) public access to medical knowledge on the Internet; (2)
      change in what constitutes medical knowledge; and (3) the impending shortage of
      educators. Some approaches are proposed, including veterinary examples, to the
      challenges presented by these changes.

PMID- 14976617
TI  - The use of information technology in large animal veterinary education.
AB  - To facilitate large animal veterinary education, information technology has to
      connect the classroom to the farm. Technology needs to be portable, durable, and
      cost-effective. Dairy production medicine was one of the first areas in
      veterinary medicine to use computers to manage large sets of milk production
      related data. Now equine practice has embraced technology in almost every
      diagnostic imaging methodology. The personal desktop assistant (PDA) has allowed
      students to take large volumes of information with them during clinical
      rotations. The technology is advancing so quickly that it is difficult to keep up
      with new software and hardware developments, let alone purchase the most current
      versions. This article reviews information technology as it is used in large
      animal practice and, consequently, in large animal veterinary education.

PMID- 14976618
TI  - Information technology in veterinary pharmacology instruction.
AB  - Veterinary clinical pharmacology encompasses all interactions between drugs and
      animals and applies basic and clinical knowledge to improve rational drug use and
      patient outcomes. Veterinary pharmacology instructors set educational goals and
      objectives that, when mastered by students, lead to improved animal health. The
      special needs of pharmacology instruction include establishing a functional
      interface between basic and clinical knowledge, managing a large quantity of
      information, and mastering quantitative skills essential to successful drug
      administration and analysis of drug action. In the present study, a survey was
      conducted to determine the extent to which veterinary pharmacology instructors
      utilize information technology (IT) in their teaching. Several IT categories were
      investigated, including Web-based instructional aids, stand-alone pharmacology
      software, interactive videoconferencing, databases, personal digital assistants
      (PDAs), and e-book applications. Currently IT plays a largely ancillary role in
      pharmacology instruction. IT use is being expanded primarily through the efforts
      of two veterinary professional pharmacology groups, the American College of
      Veterinary Clinical Pharmacology (ACVCP) and the American Academy of Veterinary
      Pharmacology and Therapeutics (AAVPT). The long-term outcome of improved IT use
      in pharmacology instruction should be to support the larger educational mission
      of active learning and problem solving. Creation of high-quality IT resources
      that promote this goal has the potential to improve veterinary pharmacology
      instruction within and across institutions.

PMID- 14976619
TI  - One educator's perspective on the role of instructional technology in veterinary
      surgical education.
AB  - A brief overview of the history of instructional technology (IT) use in
      veterinary surgery education is followed by an assessment of the state of the art
      in this discipline in the United States. Comments on assessment of teaching tools
      and the need for a concerted effort at future assessments are made in light of
      published information regarding the success of alternative learning methods in
      education in other disciplines. A few final comments are shared about discipline
      specific technology demands in surgical education and the issue of copyrights
      versus sharing resources.

PMID- 14976620
TI  - The application of information technology in the teaching of veterinary
      epidemiology and public health.
AB  - Information technology (IT) is an imprecise term currently used to describe
      computer-based techniques for data manipulation, storage, dissemination,
      publication, and retrieval. IT possesses several characteristics that promote
      meaningful learning, including (1) just-in-time, personalized; (2) student
      centered versus teacher-centric; (3) self-paced; (4) anytime, anywhere; and (5)
      discovery (through bibliographic and other information searches). However, if
      done improperly, IT-based teaching can be counterproductive. Factors to consider
      when evaluating the effectiveness of IT-based teaching methods include (1)
      content, (2) learning, (3) delivery support, (4) usability, and (5)
      technological. IT has been used to support instruction in epidemiology and public
      health at many levels, ranging from basic computer literacy to hands-on training
      in epidemiological methods through computer-based problem sets, case workups,
      outbreak investigations, and tutorials. Online quizzes based on articles selected
      from practice-oriented journals have been used to promote evidence-based medicine
      skills, including the critical evaluation of medical claims. As online access and
      delivery improve, opportunities for substantive online education and lifelong
      learning through IT have expanded. One of the most novel and comprehensive
      implementations of collaborative online sharing of educational content in
      epidemiology and public health is the Epidemiology Supercourse
      (http://www.pitt.edu/~super1/). More than 9,000 faculty from 118 countries have
      contributed to an online library of more than 700 lectures with quality control
      and adherence to accepted pedagogic principles. The goal is to improve teaching
      and research in epidemiology and public health worldwide. Although the focus is
      on human medicine, the concepts, methods, and principles can easily be applied to
      veterinary medicine. The Association for Veterinary Epidemiology and Preventive
      Medicine (AVEPM) seeks to heighten awareness of issues in veterinary epidemiology
      and public health education among veterinary educators through various forums,
      symposia, and workshops. The AVEPM Web site (http://www.cvm.uiuc.edu/avepm/)
      includes a listing of educational software and Web sites supporting epidemiology
      and public health education.

PMID- 14976621
TI  - Developing interactive course Web sites for distance education and
      characteristics of students enrolled in distance learning courses.
AB  - The ubiquity of the Internet has made disseminating information across
      geographical boundaries a relatively easy task. Apart from text-based materials,
      the Internet provides an easy means to transmit images, sound, video, and other
      multimedia content to a global audience, making it an ideal medium for
      establishing distance learning programs. Two Internet-based distance learning
      courses were developed to teach animal physiology to veterinary technicians in
      the School of Veterinary Medicine at Purdue University. These distance learning
      course sites are designed to take advantage of multimedia technology to enhance
      students' learning experiences. Multimedia has been used in education to make the
      learning process more engaging and interactive. The two course sites have a
      number of multimedia features that complement the textual subject matter. This
      article describes the features of the course Web sites and summarizes our
      experiences in designing and conducting Web-based physiology courses to distance
      learners. In addition, we describe the characteristics of our distance learning
      students.

PMID- 14976622
TI  - International cooperation in veterinary public health curricula using web-based
      distance interactive education.
AB  - The expanding field of Veterinary Public Health places new demands on the
      knowledge and skills of veterinarians. Veterinary curricula must therefore adapt
      to this new profile. Through the introduction of case studies dealing with up-to
      date issues, students are being trained to solve (real-life) problems and come up
      with realistic solutions. At the Department of Public Health and Food Safety of
      the Veterinary Faculty at the University of Utrecht in the Netherlands, positive
      experiences have resulted from the new opportunities offered by the use of
      information and communication technology (ICT) in education. The possibility of
      creating a virtual classroom on the Internet through the use of WebCT software
      has enabled teachers and students to tackle emerging issues by working together
      with students in other countries and across disciplines. This article presents
      some of these experiences, through which international exchange of ideas and
      realities were stimulated, in addition to consolidating relations between
      universities in different countries. Long-distance education methodologies
      provide an important tool to achieve the increasing need for international
      cooperation in Veterinary Public Health curricula.

PMID- 14976623
TI  - Non-linear, visual-rich supplemental material designed for an introductory course
      in veterinary anesthesia.
AB  - A possible reason for superficial learning in an introductory anesthesia course
      was considered to be a lack of visual reinforcement at the time of examination
      preparation. Students had limited access to live animal laboratories and clinical
      cases during the course, reducing their ability to depend on experiential
      learning. In an attempt to improve student learning, simple presentation software
      was used to develop a supplemental CD. The design involved multiple PowerPoint
      presentations that incorporated text, pictures, videos, and self-assessments. Non
      linear exploration of the topics covered was made possible by extensive use of
      hyperlinks within and between presentations, moving the student to definitions,
      background material, videos, advanced details, and previously covered
      information. Comments received from students on a prototype were positive
      overall, and improvements were made related to their feedback. Other supplemental
      materials and lecture presentations can easily incorporate the techniques
      described here.

PMID- 14976624
TI  - Use of interactive online histopathology modules at different stages of a
      veterinary program.
AB  - A mixed-method educational research study was conducted to evaluate the use of a
      series of online histopathology modules by students at two levels in a
      professional veterinary medical program. The materials were hypothesized to
      support student learning of histopathology concepts by facilitating "dual coding"
      of the content, since they provide both visual and verbal information. Second-
      and fourth-year professional veterinary students were surveyed about their
      perceptions of the effectiveness, efficiency, and appeal of the online modules. A
      historical comparison of final grades in the second-year Pathology course was
      conducted to evaluate the impact of the materials on academic outcomes. Think
      aloud interviews were conducted with the fourth-year students in which the
      researcher observed the students interacting with the materials and asked them to
      "tell me what you're thinking as you use the modules." Survey results show that
      the only area in which the two student groups quantitatively rated the materials
      differently was their perception of how the materials complemented their
      learning. In contrast, the qualitative data indicate that advanced students used
      and perceived the materials differently, perhaps because of their greater
      metacognitive skills and pre-existing knowledge. We concluded that these findings
      can be attributed to the manner in which students approached the materials: the
      fourth-year students felt the materials were less relevant because they did not
      directly correspond to cases they were seeing, while the second-year students
      appreciated their relevance to topics in the Pathology course. There was no
      significant difference in final exam performance for the group of students that
      used the supplemental online modules and the prior four years' classes, who did
      not have access to the materials. Overall, this study demonstrated that it is
      possible to create a set of materials to be used by multiple audiences, provided
      the needs of each group are taken into consideration during the design process.

PMID- 14976625
TI  - Determinants of adoption and euthanasia of shelter dogs spayed or neutered in the
      university of california veterinary student surgery program compared to other
      shelter dogs.
AB  - Limited economic resources and pet overpopulation force animals shelters to
      consider euthanasia of adoptable animals every day. Veterinary medical schools
      can play a positive role in increasing pet adoption and combating overpopulation
      by providing free neutering for shelter animals. This retrospective cohort study
      illustrated that the cooperative efforts of a veterinary medicine surgical
      teaching program and local animal shelters decreases euthanasia of adoptable
      pets. At the University of California, Davis (UCD), shelter dogs are neutered by
      veterinary students and then returned to the shelter for adoption. The rates of
      adoption and euthanasia of the dogs neutered at UCD were contrasted with a
      comparison shelter group to determine the effect of pre-adoption neutering. The
      UCD-neutered dogs had a lower rate of euthanasia than the comparison shelter
      group at the shelters investigated. At Sacramento County Animal Care and
      Regulation, 73% of the UCD group but only 36% of the comparison group were
      adopted. At Yolo County Animal Services, 71% of the UCD group and 45% of the
      comparison group were adopted. The sex of an animal did not significantly affect
      the rate of euthanasia. Dogs that were predominantly pit bull, rottweiler, or
      chow chow breeds had higher rates of euthanasia than other breeds, independent of
      neuter status. Also, juveniles (less than one year old) had lower rates of
      euthanasia than adults, independent of neuter status. UCD adult dogs had lower
      rates of euthanasia than comparison adults. Post-surgical UCD dogs spent a longer
      average time in the shelter before adoption (15 days at Sacramento; 16 days at
      Yolo) than the comparison dogs (11 and 12 days, respectively). UCD dogs also
      spent a longer average time in the shelter before euthanasia (18 and 25 days,
      respectively) than the comparison dogs (13 days at both shelters). Lower
      probabilities of euthanasia for behavioral or medical reasons were found for UCD
      dogs than for the comparison dogs. The probability of euthanasia for reasons of
      space limitations increased with time in shelter for both groups. In this study,
      pre-adoption neutering increased adoptions without increasing the probability of
      medical or behavioral euthanasia.

PMID- 14976626
TI  - The educational discipline of shelter medicine.

PMID- 14976627
TI  - Veterinarians and public health: the Epidemic Intelligence Service of the Centers
      for Disease Control and Prevention, 1951-2002.
AB  - Public health affords important and exciting career opportunities for
      veterinarians. The Epidemic Intelligence Service Program (EIS) of the Centers for
      Disease Prevention and Control (CDC) is a two-year post-graduate program of
      service and on-the-job training for health professionals, including
      veterinarians, who are interested in careers in epidemiology and public health.
      EIS serves as a major point of entry into the public health arena. Veterinarians
      applying to the program must have a Master of Public Health or equivalent degree,
      or demonstrated public health experience or course work. EIS officers are
      assigned to positions at CDC headquarters or in state and local health
      departments. During two-year assignments, they are trained in applied
      epidemiology, biostatistics, conducting outbreak investigations, emergency
      preparedness and response, and scientific communications. They conduct
      epidemiologic outbreak and other investigations, perform applied research and
      public health surveillance, serve the epidemiologic needs of state health
      departments, present at scientific and medical conferences, publish in the
      scientific literature, and disseminate vital public health information to the
      media and the public. EIS officers apply their training and skills to actual
      public health problems and issues, establish mentorships with recognized experts
      from CDC and other national and international health agencies, and travel
      domestically and internationally. Since 1951, 195 veterinarians have graduated
      from the program and gone on to make substantial contributions to public health
      in positions with federal, state, or local governments, academia, industry, and
      non-governmental organizations.

PMID- 14976650
TI  - Areolar connective tissue grafts in pediatric tympanoplasty: a pilot study.
AB  - PURPOSE: To compare the surgical and audiologic success rates of areolar
      connective tissue with temporalis fascia in pediatric tympanoplasty. METHODS:
      Retrospective case series review of 10 patients younger than 18 years who
      underwent primary tympanoplasty between December 1997 and December 2000 using
      areolar connective tissue grafts. Tympanoplasty patients receiving temporalis
      fascia grafts during this period were used as a control group. Surgical and
      audiometric results were gathered after a minimum follow-up of 1 year. RESULTS:
      Both groups were similar in their clinical characteristics (P <.05). The surgical
      success rates for areolar and temporalis fascial groups were 90% and 91%,
      respectively. Closure of the air bone gap to within 25 dB was achieved in 90% and
      91% of the areolar and temporalis fascial groups, respectively. CONCLUSIONS: This
      study showed equivalent surgical and audiometric success rates between areolar
      connective tissue and temporalis fascia. Both are excellent sources of graft
      material in pediatric patients.

PMID- 14976651
TI  - Complications of cochlear implant placement with minimal hair shave.
AB  - OBJECTIVE: The goal of this study was to determine if a change to minimal-hair
      shave preparation has altered the incidence of complications after cochlear
      implant surgery. MATERIALS AND METHODS: Charts were reviewed on 158 consecutive
      patients that underwent primary cochlear implant surgery for evidence of minor
      and major surgical complications with full- or minimal-hair shave preparation.
      RESULTS: Complications were noted within 6 weeks in 5 of 105 patients in the
      minimal-hair shave group and 3 of 53 in the full-hair shave group (4.8% v 5.7%, P
      =.53). Delayed complications were noted in 3 within the minimal-shave group and 1
      within the full-shave group (2.9% v 1.9%, P =.58). Only 1 wound complication
      required replacement of the cochlear implant. CONCLUSIONS: There is no evidence
      that minimal-hair shave adversely affects rates of wound complications in patents
      undergoing cochlear implant surgery. Therefore, minimal preoperative scalp shave
      may be an acceptable alternative to the traditional hair shaving technique.

PMID- 14976652
TI  - Total laryngectomy and postoperative radiotherapy for T4 laryngeal cancer: a 14
      year review.
AB  - OBJECTIVE: The most appropriate treatment of locally advanced carcinoma of the
      larynx remains to be ascertained. Management of T4 laryngeal cancer patients with
      postoperative radiotherapy after total laryngectomy is generally advocated and
      not often debated. However, the effects of this combined treatment approach are
      poorly documented. We reviewed the oncologic outcome and long-term survival of
      individuals treated by total laryngectomy and postoperative radiotherapy (TLPR)
      for T4 carcinoma of the larynx. METHODS: Twenty-eight patients with a pathologic
      diagnosis of T4 laryngeal cancer treated by TLPR during a 14-year period were
      studied retrospectively. Median follow-up from treatment until the end of
      observation was 36 months (range 6 to 123 months). RESULTS: The overall actuarial
      and disease-free survival rates at 7 years were 43% and 30%, respectively. Local
      recurrence, regional relapse, and distant metastasis developed in 4%, 4%, and 7%
      of the cases, respectively. Later esophageal stricture, dental caries, or carotid
      artery disease in 3 patients (11%) was successfully managed. Multivariate
      analysis showed patient age, bilateral true vocal cord-anterior commissure
      involvement by laryngeal cancer (horse-shoe lesion), and any type of treatment
      failure to be the most predictive variables affecting prognosis. CONCLUSION: Long
      term disease control and survival is achievable by TLPR with minimal late
      toxicity in patients with T4 carcinoma of the larynx.

PMID- 14976653
TI  - The impact of race on survival in nasopharyngeal carcinoma: a matched analysis.
AB  - OBJECTIVE: To determine if nasopharyngeal carcinoma (NPC) exhibits significant
      prognostic differences in Chinese versus white patients. METHODS: From the
      Surveillance, Epidemiology, and End Results database for the time period 1988 to
      2000, all cases of NPC were extracted and staging variables computed. To each
      case of NPC diagnosed in a Chinese patient, a case of NPC in a white patient was
      randomly matched for age at diagnosis, gender, grade, stage, and treatment
      modality. Kaplan-Meier survival analysis was then conducted for the matched
      groups comparing overall survival and disease-specific survival both for the
      overall matched cohort and stage stratified cohorts. RESULTS: Among 1,520 cases
      of NPC, 338 were identified in Chinese patients with staging information. Of
      these, 171 were successfully matched to white patients. Average age at
      presentation was 51.5 years with a 3:1 male predominance. Overall survival was
      substantially better for Chinese patients (mean survival, 94 months; median
      survival, 95 months) than for white patients (81 months and 64 months, P =.037).
      Stratified for stage, overall survival was better for Chinese patients for stage
      3 but not stage 4 disease (P =.012 and P =.447, respectively). Disease-specific
      survival was not substantially different between Chinese patients (mean survival,
      116 months) and white patients (mean survival 117 months, P =.99). No differences
      in disease-specific survival were identified for race when stratified by stage
      (all P >.05). CONCLUSIONS: Although overall survival is better for Chinese
      patients with NPC compared with white patients, disease-specific survival is
      similar between these racial groups. These data suggest that the biological
      behavior of NPC is relatively independent of race.

PMID- 14976654
TI  - Supracricoid laryngectomy: is it time to define guidelines to evaluate functional
      results? a review.
AB  - PURPOSE: Supracricoid laryngectomy (SCL) permits local control and 5-year
      survival rates similar to total laryngectomy in selected cases of advanced-stage
      laryngeal carcinoma. Although most of the reports regarding the surgical
      technique and oncological results have been proposed by European groups,
      increased interest in SCL has also been shown in recent years by American
      surgeons. There is still a lack of comprehensive studies about functional
      outcomes (respiration, deglutition, phonation) after SCL. Materials and methods
      This report briefly evaluates the functional outcomes of SCL recorded by the
      Department of Otolaryngology Head and Neck Surgery of Padua University since 1998
      and critically reviews recent English-language literature describing SCL
      functional results. RESULTS: The present review confirms that the available data
      on functional results were collected using heterogeneous methods, parameters, and
      evaluation scales. CONCLUSIONS: Every effort has to be made to uniform the format
      for presenting outcome data, particularly on swallowing and voice parameters.
      Defining guidelines to evaluate the functional results of SCL may facilitate
      interstudy comparability.

PMID- 14976655
TI  - Delayed peripheral facial palsy in the stapes surgery: can it be prevented?
AB  - PURPOSE: The aim of this study was to evaluate poststapedectomy-delayed facial
      palsy etiopathogenesis, risk factors, evolution, and prevention. MATERIALS AND
      METHODS: Seven hundred six stapedectomies performed in 580 patients were
      reviewed. In all patients who developed delayed facial palsy, the dates of onset
      and subside of facial palsy, the anatomic and pathologic predisposing factors,
      and a possible history for recurrent labial herpetic lesions were considered. The
      House-Brackmann (H-B) grading system was used to evaluate the facial function.
      Virus-specific immunoglobulin (Ig) G and IgM antibodies against herpes simplex
      virus type 1 (HSV-1) were determined by enzyme-linked immunosorbent assay (ELISA)
      3 weeks after the onset of the paralysis. The results were compared with a
      control group without a history of recurrent herpes labialis. RESULTS:
      Poststapedectomy facial palsy developed in 7 out of 706 procedures. All 7
      patients referred a history of recurrent labial herpetic lesions. One patient
      showed a facial palsy H-B grade II, 2 a grade III, and 3 a grade IV. After
      acyclovir therapy, 6 subjects recovered completely, whereas 1 maintained an H-B
      grade II. An increased IgG antibody titer was found in 6 of the patients with
      delayed facial palsy and in 1 out of 7 controls. Mean IgG titer was 1:14,050 in
      the subjects with delayed facial palsy and 1:2,300 in controls (P <.001).
      CONCLUSIONS: Poststapedectomy-delayed facial palsy is likely caused by a
      reactivation of HSV-1, latent within the geniculate ganglion. The activation of
      the latent virus is more frequent in patients with a history of herpes labialis
      and can be prevented by an adequate acyclovir therapy.

PMID- 14976656
TI  - Three-dimensional computed tomography imaging of Eagle's syndrome.

PMID- 14976657
TI  - Posttympanostomy tube otorrhea.
AB  - This article will focus on some theories and recent advances to explain chronic
      post tympanostomy tube otorrhea, a step-wise approach to treatment and future
      research areas of interest.

PMID- 14976658
TI  - Pleomorphic adenoma of the nasal septum: a case report.
AB  - Pleomorphic adenomas arise most commonly in the major salivary glands; the minor
      salivary glands are affected in only 8% of the cases. Intranasal pleomorphic
      adenoma being extremely rare originates most commonly from the nasal septum. We
      present a case of a 55-year-old man who presented with complaints of right-sided
      nasal obstruction and occasional nasal bleed for the last 6 months. Examination
      showed a mucosa-covered, fleshy 2 x 2 x 1.5 cm mass in the right nasal cavity.
      Computed tomogram showed right-sided polypoidal mass with attachment to the
      cartilaginous nasal septum without any erosion of the surrounding structures. The
      clinical presentation, gross and microscopic appearance, and treatment of
      intranasal pleomorphic adenoma is briefly discussed.

PMID- 14976659
TI  - B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma presenting in the
      tonsil: a case report and review of literature.

PMID- 14976660
TI  - Mediastinal compression secondary to supraglottitis: a case report.
AB  - Potential fascial spaces of the neck communicate inferiorly with the mediastinum
      and thus provide a route for spread of infections. It is very uncommon for
      supraglottitis to spread to one of these spaces. In this rare case, this
      infection not only involved the parapharyngeal space but also followed the
      anatomic path down to the mediastinum. The resulting mediastinal edema increased
      the intrathoracic pressure and thus upset the hemodynamic. Despite being in
      critical condition due to pulmonary edema and hypotension, the patient recovered
      without the use of aggressive surgical measures recommended for such cases.

PMID- 14976661
TI  - Metastatic neuroendocrine tumors of the parotid gland.
AB  - OBJECTIVES: To present 2 cases of neuroendocrine tumors of the parotid gland and
      to review the clinical presentation, histopathologic, and immunohistochemical
      findings and treatment of these rare tumors. STUDY DESIGN: Case series. METHODS:
      This study reviews 2 patients who both presented with firm masses in the parotid
      gland diagnosed as neuroendocrine carcinoma by histopathologic and
      immunohistochemical examination. The evaluation, diagnosis, and treatment are
      discussed. RESULTS: Both patients underwent complete tumor extirpation via a
      total or subtotal parotidectomy. Both patients received postoperative radiation
      therapy and chemotherapy. CONCLUSIONS: Neuroendocrine tumors of the parotid gland
      are uncommon lesions; however, they have a favorable prognosis as compared to
      their pulmonary counterparts with early diagnosis and aggressive treatment.
      Diagnosis is based on the immunohistochemical characteristics of the tumor.
      Appropriate treatment includes complete surgical excision with postoperative
      radiation therapy to the parotid bed with the addition of postoperative
      chemotherapy in patients suspected to have metastatic disease.

PMID- 14976662
TI  - Dirofilarial infection presenting as a facial mass: case report of an emerging
      zoonosis.
AB  - Dirofilariasis is a parasitic infection caused by nematodes. Human infection
      remains rare but is increasing in scope, particularly in endemic areas.
      Dirofilariasis typically presents as a subcutaneous mass or with pulmonary
      nodules. Here, we present the case of a 73-year-old woman whose asymptomatic
      facial mass was caused by dirofilarial infection. The pathophysiology, diagnosis,
      and treatment of dirofilariasis of the head and neck will be discussed. In
      endemic areas, dirofilariasis must be considered in the differential diagnosis of
      facial masses.

PMID- 14976663
TI  - Dynamic voice assessment using flexible laryngoscopy--how I do it: a targeted
      problem and its solution.

PMID- 14976664
TI  - Hearing loss and vertigo in superficial siderosis of the central nervous system.
AB  - PURPOSE: Otoneurologic findings in patients with superficial siderosis (SS) of
      the central nervous system are described. A 20-year-old man with acute vertigo,
      dizziness, with a history of head trauma in childhood; an 87-year-old woman with
      severe disequilibrium appearing after peridural anesthesia; and a 55-year-old
      woman with recurrent episodes of positional vertigo and progressive ataxia,
      suffering from a lumbar ependymoma are described; all patients complained of
      progressive bilateral hearing loss and tinnitus. Methods and results
      Otoneurologic examination showed bilateral sensorineural hearing loss, disturbed
      ocular pursuit and optokinetic nystagmus, incomplete visual suppression of the
      vestibulo-ocular reflex during rotatory pendular testing, right hyporeflexia, and
      bilateral caloric areflexia. Cerebral magnetic resonance imaging (MRI) revealed
      rims of hypointensity surrounding the brainstem and linear hypointensities
      following the surface of the cerebellar folia. CONCLUSIONS: The etiology stems
      from subarachnoid hemorrhage, but the source of bleeding may remain obscure.
      Bilateral hearing loss is described in 95% and disequilibrium in 90% because of
      peripheral vestibular deficit and cerebellar ataxia. In patients with progressive
      bilateral cochleo-vestibular deficit of unknown etiology, MRI is the examination
      of choice to confirm SS.

PMID- 14976671
TI  - Worsened agitation with aripiprazole: adverse effect of dopamine partial agonism?

PMID- 14976672
TI  - [Review of the activities from the former State Institute for Serum Production].
AB  - This article describes the foundation and development of the State Institute for
      Serum Production (Rijksseruminrichting) in Rotterdam, the Netherlands, during the
      period 1904-1959. It describes the work of Dr J. Poels, the founder of the
      Institute, and the production of antisera in terms of the selection of animals,
      immunization protocols, blood sampling and collection, and the preservation and
      use of antisera in practice. Attention is also paid to the production of vaccines
      and diagnostic tests and to research on animal diseases. Envisaged research goals
      were not achieved because of a lack of adequate financial support and staffing,
      and poor laboratory facilities.

PMID- 14976673
TI  - [Predecessors: veterinarians from earlier times (53). Dirk Frederik van Esveld
      (1848-1912)].

PMID- 14976674
TI  - [The future of veterinary medicine, seen by the 'regular mixed practitioner'].

PMID- 14976675
TI  - [Seven hundred black pages of veterinary medicine].

PMID- 14976676
TI  - [BVD-approach: the helm is the other way].

PMID- 14976677
TI  - [Aerodynamics does not drop the bumble bee].

PMID- 14976678
TI  - ['Bumblebee-o-pathic' reasoning].

PMID- 14976679
TI  - [Vision through cooperation between horse clinics].

PMID- 14976680
TI  - [Infections with endoparasites in dogs in Dutch animal shelters].
AB  - Faecal samples from 224 dogs from 23 animal shelters in the Netherlands were
      examined for endoparasites. In total 20.5% of the faecal sample were positive for
      helminth and/or protozoa infections. Eggs of Toxocara canis were found in 8.5% of
      the faecal samples. Other endoparasites found were Toxascaris leonina (0.5%),
      Trichuris vulpis (4.9%), Uncinaria stenocephala (2.2%), Dipylidium caninum
      (1.3%), Taenia spp. (0.5%), Cystoisospora canis (1.3%), and C. ohioensis (1.3%).
      Dogs younger than 1 year and stray dogs showed the highest prevalence of
      infection. T. vulpis was found more often in dogs from shelters with a high
      cleaning frequency.

PMID- 14976681
TI  - [Horse inspection: approved or badly judged?].

PMID- 14976682
TI  - [A stone in the BVD pond. Vaccination as weapon against BVD].

PMID- 14976683
TI  - [The future of veterinary medicine in the Netherlands].

PMID- 14976684
TI  - [Interview with the incoming general director Herman Geertsen. "Teamwork is an
      important buzz word." Interview by Susan Umans].

PMID- 14976685
TI  - The varieties of clinical consulting experience.

PMID- 14976686
TI  - Joining the team: ethics consultation at the Cleveland Clinic.
AB  - In this paper, I describe the development of ethics consultation services and
      their operation at the Cleveland Clinic; my own educational experiences and
      background and how I came to see the importance of setting and collaboration for
      successfully doing clinical ethics; the unique culture of the Cleveland Clinic
      and its influence on the ethics consultation services provided there; and,
      finally, the place of personal commitments and values on the conduct of ethics
      consultations. I stress the point that although philosophers (and perhaps other
      bioethicists without health professions training) are socialized and educated to
      do solitary work, successfully conducting ethics consultations requires
      relatively high levels of collaboration and cooperation that have not been
      sufficiently discussed. Although this paper is more a description than an
      analysis of the influence of institutional setting on ethics consultation, I
      would claim that attention to setting, either as the local scene of the
      consultation or the institutional and social framework, deserves more attention
      by bioethicists intent on understanding ethics consultation.

PMID- 14976687
TI  - Catholic health care ethics consultation: a community of care.

PMID- 14976688
TI  - Clinical consulting: the search for resolution at the intersection of medicine,
      law, and ethics.

PMID- 14976689
TI  - Pilgrimage and profession.

PMID- 14976690
TI  - The bioethics consultant: giving moral advice in the midst of moral controversy.

PMID- 14976691
TI  - Change and the learning organization.

PMID- 14976692
TI  - A retrospective study of left ventricular assist device-related infections.
AB  - Left ventricular assist devices (LVADs) represent considerable technological
      advancements, which are increasing survival and maintaining the highest quality
      of life for patients with chronic heart failure. A retrospective analysis of
      outcomes was conducted on 90 patients during LVAD support with either a Thoratec
      (n = 41) or HeartMate (n = 49) device, with a median of 56 days (range 3-350
      days). Device-related infections occurred in 18 of the 90 subjects (20%). A
      significant increase in device-related infections was noted with the HeartMate
      LVAD (chi 2 analysis, P < .05). The drive line was the most common site of device
      related infections, accounting for 52.1%, with 31.1% occurring in the pocket and
      15.1% in the LVAD itself. There was little if any correlation that existed
      between time spent in the hospital prior to implantation of an LVAD and the
      development of device-related infections.

PMID- 14976693
TI  - Riding the storms--approaching cardiac intervention: combining an information
      based managerial perspective with a knowledge-based expert view.
AB  - To contribute to an improvement of efficiency within the health care system, it
      is important for each medical professional involved in a specific value chain of
      cure to have some basic understanding of the related and updated treatment
      methods. In a relatively short time, the field of interventional cardiology has
      evolved into an independent clinical discipline with a wide variety of
      therapeutic modalities. At present, it is possible to safely treat lesions in the
      main stem of the left coronary artery with percutaneous transluminal angioplasty.
      The risk of thrombosis and restenosis following stent delivery has been
      significantly reduced by the introduction of several new pharmacological agents
      and improvement in the design of the stents. In addition, it has been confirmed
      that primary angioplasty in acute myocardial infarction has a superior outcome
      compared with thrombolysis. The aforementioned historical overview is highlighted
      from an integrated managerial and clinical perspective.

PMID- 14976694
TI  - Advocate health care's intranet: meeting four common challenges.

PMID- 14976695
TI  - Gartner releases study on Web strategies of healthcare organizations.

PMID- 14976696
TI  - An exception to the rule.

PMID- 14976697
TI  - When I grow up I want to be....

PMID- 14976698
TI  - Up and at 'em.

PMID- 14976699
TI  - Public priorities.

PMID- 14976701
TI  - The harder they fall.

PMID- 14976700
TI  - Home from home.

PMID- 14976702
TI  - Training needs analysis: an evaluation framework.
AB  - Training needs analysis (TNA) is the first step in the training and educational
      strategy of an organisation and is crucial to meeting the continuing professional
      development needs of the healthcare workforce and service. TNA must be carefully
      planned, conducted and have clear outcomes to ensure that training interventions
      are implemented effectively and that they lead to meaningful changes in service
      delivery. However, there is a death of literature on approaches to critique TNA.
      This article describes a framework developed specifically to evaluate the
      effectiveness of TNA. The framework combines approaches that have been used to
      evaluate conventional research studies and audit.

PMID- 14976703
TI  - Use of convex appliances.

PMID- 14976704
TI  - Enteral feeding and percutaneous endoscopic gastrostomy.
AB  - Many patients are unable to eat and others are malnourished. Such patients need
      nutritional support, and enteral feeding offers one way of providing such
      support. It may be needed for a short time during acute or critical illness or
      for prolonged periods in chronic illness. Short-term feeding is usually given
      through a nasogastric tube, while permanent feeding access is indicated for long
      term feeding, most commonly through a gastrostomy. Percutaneous endoscopic
      gastrostomy (PEG) is a minimally invasive technique for placing a feeding tube
      and causing minimal discomfort. This article reviews enteral feeding focusing on
      PEG and considers the after care and complications of this method of feeding.

PMID- 14976705
TI  - Obesity in children.
AB  - This article reviews the causes of childhood obesity and suggests different
      approaches to treatment and prevention.

PMID- 14976706
TI  - Intense care.

PMID- 14976707
TI  - Soft-tissue infection: necrotizing fasciitis.
AB  - Necrotizing fasciitis (NF) is a potentially fatal infection of the skin and soft
      tissue. The early presentation may first appear as cellulitis. The skin stays
      intact in the early stages of NF; this leads to a deceptive benign appearance.
      The skin typically appears red, hot and exquisitely tender. Blisters may or may
      not be present. Severe local pain, which is out of proportion to the size and
      type of wound, is a hallmark sign seen in NF. Recognition of the signs and
      symptoms, as well as timely diagnosis and treatment of this condition is
      imperative. This is necessary in order to assist in preventing widespread tissue
      destruction, and enhance favorable patient outcomes. The purpose of this paper is
      to increase the knowledge and understanding of NF and to discuss the nurses' role
      in minimizing unfavorable outcomes.

PMID- 14976708
TI  - Occupational transmission of hepatitis B.

PMID- 14976709
TI  - Making sense of glove selection.

PMID- 14976710
TI  - Alternative sources of biologically active substances.
AB  - The majority of antibiotics and substances with diverse biological activity used
      in medicine are produced by actinomycetes, nonfilamentous bacteria and fungi.
      Other microorganisms, such as myxobacteria, pseudomonads, nocardias,
      basidiomycetes, marine microorganisms, enterobacteria, halobacteria,
      hyperthermophiles etc. are investigated for new biologically active metabolites.

PMID- 14976711
TI  - Spore-specific modification of DNA-dependent RNA polymerase alpha subunit in
      streptomycetes--a new model of transcription regulation.
AB  - At the very beginning of spore germination in streptomycetes the full-length
      alpha subunit of DNA-dependent RNA polymerase is shortened from its C-terminus.
      The C-terminal domain of the protein is required for binding of DNA and
      transcription regulators but its regulatory role in streptomycetes was not
      extensively studied. Comparison of the sequences of E. coli and S. coelicolor RNA
      polymerase alpha subunit (RNAP alpha) C-terminal domains reveals that the
      majority of amino acid residues responsible for the interaction with
      transcription regulators is conserved in both microorganisms. The spore specific
      modification of streptomycete RNAP alpha could thus have its regulatory role. The
      nature of the proteolytic enzyme, responsible for the RNAP alpha cleavage is
      discussed.

PMID- 14976712
TI  - Production, partial purification and some properties of beta-galactosidase from
      Aspergillus carbonarius.
AB  - Production of beta-galactosidase by Aspergillus carbonarius grown on
      deproteinized cheese whey as basal medium was optimized (cultivation period of 6
      d, pH 4.5, cultivation temperature 30 degrees C). The enzyme was partially
      purified (52.9-fold with an overall yield of 45.3% and a final specific activity
      of 4588 mu kat/g protein. The optimum pH for the enzyme activity was pH 4.5. The
      enzyme is to some extent thermostable. Metal ions are not required for enzyme
      activity. The enzyme may be considered for prospective use in food industry.

PMID- 14976713
TI  - Antimycobacterial activity of piperidinylpropyl esters of alkoxy-substituted
      phenylcarbamic acids.
AB  - A series of 17 hydrochlorides of piperidinylpropyl esters of alkoxy-substituted
      phenylcarbamic acids with the alkoxy group in position 2, 3 or 4 on the phenyl
      ring, and basic substituents attached to the moiety in position 3, were evaluated
      for in vitro antimycobacterial activity against the strains of Mycobacterium
      tuberculosis, M. kansasii and M. avium. To describe the structure
      antimycobacterial activity relationships (QSAR), an approach based on the Free
      Wilson method was employed to express the differences between individual moieties
      (including propyl and ethyl). The change of ethyl to propyl moiety increases the
      activity to M. tuberculosis but decreases the antimycobacterial activity to all
      potentially pathogenic strains under study.

PMID- 14976714
TI  - Role of strategic cysteine residues in oxidative damage to the yeast plasma
      membrane H(+)-ATPase caused by Fe- and Cu-containing Fenton reagents.
AB  - Damage caused to Saccharomyces cerevisiae SY4 plasma membrane H(+)-ATPase by Fe-
      and Cu-Fenton reagents was determined in secretory vesicles containing enzyme in
      which Cys residues were replaced singly or in pairs by Ala. Cys-221 situated in a
      beta-sheet domain between M2 and M3 segments, phosphorylation domain-located Cys
      409 and Cys-532 situated at the ATP-binding site play a role in the inactivation.
      In the presence of all three residues the enzyme exhibited a certain basic
      inactivation, which did not change when Cys-532 was replaced with Ala. In mutants
      having intact Cys-532 but lacking one or both other cysteines, replacement of Cys
      221 with Ala led to lower inactivation, suggesting that Cys-221 may serve as a
      target for metal-catalyzed oxidation and intact Cys-532 promotes this target role
      of Cys-221. In contrast, the absence of Cys-409 caused higher inactivation by Fe
      Fenton. Cys-532 thus seems to serve as a target for Fe-Fenton, intact Cys-409
      causing a conformational change that makes Cys-532 less accessible to oxidation.
      The mutant lacking both Cys-221 and Cys-409 is more sensitive to Fe-Fenton than
      to Cu-Fenton and the absence of both Cys residues thus seems to expose presumable
      extra Fe-binding sites. These data and those on protection by ATP, ADP, 1,4
      dithiothreitol and deferrioxamine B point to complex interactions between
      individual parts of the enzyme molecule that determine its sensitivity towards
      Fenton reagents. ATPase fragmentation caused by the two reagents differed in that
      the Fe-Fenton reagent produced in Western blot "smears" whereas the Cu-Fenton
      reagent produced defined fragments.

PMID- 14976715
TI  - Alternative reproduction pathway in Aspergillus nidulans.
AB  - Recombinant haploid segregants were recovered in filamentous fungus Aspergillus
      nidulans (Eidam) G. Winter directly from the heterokaryons instead of diploid
      segregants (process described earlier as parameiosis). In spite of the
      reproductive complexity of A. nidulans, parameiosis has only now been observed in
      this fungus. Since parameiosis was characterized by the occurrence of genetic
      recombination inside heterokaryotic hyphae, master strains (uvs+) and uvs mutants
      with high rate of both mitotic exchanges or chromosome nondisjunction were used
      to form heterokaryons. Two groups of mitotic segregants were recovered directly
      from heterokaryons--aneuploids and stable haploids. Heterokaryons formed with uvs
      mutants produced a higher number of parameiotic segregants compared to the
      heterokaryons formed with uvs+ strains. Segregants were analyzed by nutritional
      markers, acriflavine resistance and conidial color. Normal meiotic behavior of
      haploid recombinants was observed.

PMID- 14976716
TI  - Two plant alkaloids isolated from Corydalis longipes as potential antifungal
      agents.
AB  - The alkaloids N-methylhydrasteine hydroxylactam and 1-methoxyberberine chloride
      were isolated from Corydalis longipes. Both alkaloids showed high efficacy
      individually (in concentration of 50-150 ppm) and also in a 1:1 mixture against
      spore germination of some fungi, viz. Alternaria alternata, A. brassicae,
      Curvularia maculans, Curvularia sp., Colletotrichum gloeosporioides,
      Colletotrichum sp., Helminthosporium speciferum, H. pennisetti, Helminthosporium
      sp., and Ustilago cynodontis. The antifungal effect of single compounds was dose
      dependent. If the mutual ratio of the two components in the mixture was changed
      from 1:1 to a major content of any of the two compounds, the inhibitory effect on
      spore germination decreased.

PMID- 14976717
TI  - Infections with the ascomycete fungus Metschnikowia typographi sp.nov. in the
      bark beetles Ips typographus and Ips amitinus (Coleoptera, Scolytidae).
AB  - The ascomycete fungus Metschnikowia typographi sp.nov. is described. It infects
      the spruce bark beetles Ips typographus L. and Ips amitinus Eichl. Masses of
      vegetative cells and navicular asci (I. typographus 13-17 x 2 microns; I.
      amitinus 17-22 x 2 microns) were found in cells of the midgut epithelium and in
      the body cavity of infected beetles. Each ascus contains two needle-shaped
      ascospores flattened in the central part, 0.5-1.5 x 0.3 x 13-15 microns and
      pointed at both ends. The parasitic species of Metschnikowia, M. bicuspidata, M.
      artemiae, M. unicuspidata, M. wickerhami and M. typographi are discussed as a
      special group of the genus characterized by morphological characters.

PMID- 14976718
TI  - Cell differentiation and colony alteration of an edible terrestrial
      cyanobacterium Nostoc flagelliforme, in liquid suspension cultures.
AB  - Morphological characteristics of an edible terrestrial cyanobacterium Nostoc
      flagelliforme in liquid suspension cultures under photoautotrophic conditions are
      presented. Different cell forms alternated in a regular manner during the
      experimentation period (30 d). N. flagelliforme exhibited a very complex life
      cycle in terms of colony morphology, including mainly 4 different colony
      morphological forms, viz. hormogonia, filaments, seriate colonies and aseriate
      colonies. Under laboratory conditions it formed spherical colonies on solid media
      but not threadlike colonies as it did under natural conditions. The overall life
      span of the alga was not altered by the existence of different nitrogen sources
      in the media despite the depression of some cell forms or colony morphologies.
      Compared with growth on the medium with urea and ammonium as nitrogen sources,
      the alga on standard medium had a short period of hormogonia and aseriate colony,
      suggesting that both ammonium and urea could stimulate the formation of
      hormogonia, at the same time inhibiting the formation of heterocystous cells. The
      new information on the growth and morphology of N. flagelliforme could be
      potentially used for the scale-up or field cultivation.

PMID- 14976719
TI  - Extracellular alkaline phosphatase from the filamentous fungus Aspergillus
      caespitosus: purification and biochemical characterization.
AB  - Among 30 species of filamentous fungi isolated from Brazilian soil, Aspergillus
      caespitosus produced and secreted the highest levels of alkaline phosphatase in
      culture medium supplemented with xylan. The extracellular alkaline phosphatase
      was purified by DEAE-cellulose and concanavalin A-sepharose chromatography. The
      enzyme was a glycoprotein containing up to 56% sugar with molar mass of 134.8
      kDa, according to gel filtration in Sepharose CL-6B, and 57 kDa according to SDS
      PAGE. Nondenaturing electrophoresis (6% PAGE) of the purified enzyme produced a
      single band, suggesting that the native enzyme was a homodimer. Optima of
      temperature and pH were 75 degrees C and 8.5, respectively. The enzyme was stable
      at 50 degrees C and its activity was enhanced by 95% in the presence of Mg2+ (1
      mmol/L). 4-Nitrophenyl phosphate was the preferentially hydrolyzed substrate with
      K(m) and upsilon lim values of 74 mumol/L and 285 mumol/s, in the absence, and 90
      mumol/L and 418 mumol/s, in the presence of Mg2+, respectively. The enzyme also
      hydrolyzed other phosphorylated amino acids (O-phosphothreonine, O
      phosphotyrosine, O-phosphoserine).

PMID- 14976720
TI  - Kinetics of soluble glucan production by Claviceps viridis.
AB  - Among 18 tested strains of Claviceps spp., 7 produced significant amounts of
      exocellular polysaccharide (EPS). The maximum production of EPS was found in
      fermentation broth of Claviceps viridis. The kinetics of growth, substrate
      consumption, and EPS production in the batch, aerobic, submerged culture of this
      fungus were investigated in detail. The experimental data were processed by a
      simple mathematical model describing mass balance of growth, substrate
      consumption, formation of intermediates, and production of EPS. The parameters of
      the model were estimated from data obtained in cultivation performed in flasks
      and two laboratory fermentors of different size. Physiological similarity was
      obtained during process scale-up in volumetric ratio 1:100. The sugar consumption
      efficiency (52%) and observed EPS productivity (1.9 kg/m3 per d) were comparable
      with literature data.

PMID- 14976721
TI  - Decolorization of textile dyeing wastewater by Phanerochaete chrysosporium.
AB  - The potential use of fungal pellets for decolorization of the textile dyeing
      wastewater was evaluated. The live pellets of the fungus Phanerochaete
      chrysosporium were found to remove more than 95% of the color of this wastewater
      within 1 d. The dye-removal capacity was a function of time and was proportional
      to the agitation rate; the optimum temperature was 30 degrees C. Both live and
      dead pellets were further examined in a repeated-batch mode for 5 d. The
      decolorization performance of live pellets remained high and stable for 5 d and
      they showed twice to thrice higher decolorization capacity than dead pellets.

PMID- 14976722
TI  - Effect of disinfectants on the metabolism of Salmonella enterica serovar
      enteritidis.
AB  - Antimicrobial activity of 19 commercially manufactured disinfectant substances on
      a Salmonella enteritidis strain was determined. The substances represented 8
      quaternary ammonium salts (QAS) and 10 QAS combined with other additives. The
      antimicrobial efficacy was characterized by influencing the growth of bacterial
      cells expressed as MIC and ED50 values as well as by the inhibition of the
      incorporation rate of 14C-adenine and 14C-leucine. According to their efficacy
      the disinfectants were divided into three groups: (1) substances with strong
      inhibitory effect (MIC 6-45 micrograms/L) such as Diesin forte, Hexaquart plus,
      Neoquat S, Triquart, Almyrol, Hexaquart S, ID212, ID213 and Microbac forte; (2)
      substances with good antibacterial efficacy (MIC 90-780 micrograms/L); (3)
      substances with MIC values > 780 micrograms/L (up to 3120 micrograms/L).
      Cetrimide had very low activity (MIC 3.12-6.25 mg/L). The effect of disinfectants
      on the biosynthetic processes was expressed by R values (IC50(Ade):IC50(Leu));
      all these values were < 1 except Benzalkonium chloride, FD312, Divoquat forte, 5P
      plus, Almyrol, Hexaquart S and Hexaquart plus. Low R values suggested
      interference of these substances with the synthesis of both nucleic acids and
      proteins. All substances except 5P plus caused an inhibition of endogenous
      respiration. The most effective were Almyrol, Diesin forte, Microbac forte and
      Neoquat which completely inhibited respiration at 190 mg/L. Kvart showed the
      lowest effect on the respiration over the whole concentration range. The
      disinfectants also suppressed growth of S. enteritidis, probably by interfering
      with energy-yielding and-requiring processes in the cells.

PMID- 14976723
TI  - The effects of magnesium, calcium and EDTA on slime production by Staphylococcus
      epidermidis strains.
AB  - Effect of magnesium, calcium and EDTA on slime production by 15 slime-positive
      and 13 slime-negative Staphylococcus epidermidis strains isolated from various
      clinical specimens was determined. The slime production on tryptic soy broth was
      significantly enhanced after addition of 128 mumol/L Mg2+. Similarly, the
      addition of Ca2+ caused a significant increase in slime production of all tested
      strains when concentration of Ca2+ exceeded 64 mumol/L. In contrast, in the
      presence of EDTA the slime production by all strains was significantly reduced.
      Hence Ca2+ and Mg2+ increase slime production of S. epidermidis. This finding is
      important in the context of the pathogenesis of biomedical implant infections
      caused by S. epidermidis.

PMID- 14976724
TI  - Exposed and hidden lectin-binding epitopes at the surface of Borrelia
      burgdorferi.
AB  - The presence of surface- and subsurface-located lectin-binding epitopes of
      Borrelia burgdorferi was examined by electron microscopy using a variety of gold
      labeled lectins. Concanavalin A reacted predominantly with extracellular material
      adjacent to the spirochetes. Wheat germ agglutinin bound weakly to the surface of
      borreliae; however, alterations of the outer membrane by preincubation in 100 ppm
      Triton X-100 or boiling uncovered numerous periplasmic sites recognized by the
      lectin. The periplasmic flagella liberated by some cells after detergent
      treatment were labeled with concanavalin A, wheat germ agglutinin and Ulex
      europaeus agglutinin UEA-I. No surface-exposed or periplasmic epitopes for the
      lectins from Glycine max, Dolichos biflorus or Helix pomatia were detected.

PMID- 14976725
TI  - Some properties of Plesiomonas shigelloides treated with aminoglycosides.
AB  - The effect of aminoglycoside antibiotics (amikacin, gentamicin, netilmicin and
      tobramycin) at sublethal concentrations (sub-MICs) on some properties of
      Plesiomonas shigelloides strains was evaluated. All agents decreased the
      bacterial surface hydrophobicity. Amikacin (1/4 of the MIC) and netilmicin (1/4
      and 1/8 of the MIC) changed the hydrophobic character of P. shigelloides surface
      to a hydrophilic one. Treatment of the strains with aminoglycosides decreased
      also motility, netilmicin being the most effective. No significant changes were
      found in lipolytic activity of antibiotic-treated strains. In the majority of
      cases aminoglycosides increased sensitivity of bacteria to hydrogen peroxide. The
      tested antibiotics did not induce production of short-chained N-acylhomoserine
      lactones signal molecules. Aminoglycosides at sub-MICs affected important
      activities of P. shigelloides potentially associated with their virulence in
      dependence on strain, antibiotic and concentration.

PMID- 14976726
TI  - Establishment of a sepsis model following implantation of Klebsiella pneumoniae
      infected fibrin clot into the peritoneal cavity of mice.
AB  - Successful establishment of sepsis by entrapping a dose of 150 colony forming
      units of Klebsiella pneumoniae in a fibrin clot following implantation into the
      peritoneal cavity of mice is reported. The dose in the fibrin clot gave 50%
      mortality in mice, spread over a period of one week. All the infected mice showed
      positive blood culture up to 6 d post-infection; histopathology revealed
      inflammatory changes in both liver and spleen. Introduction of K. pneumoniae into
      experimental mice without entrapment in fibrin clot caused no mortality and blood
      culture remained positive only up to 2 d; histopathology of liver and spleen
      throughout the period of study showed relatively mild inflammatory changes, which
      almost cleared during 14 d post-infection. The use of the fibrin-clot model may
      thus be considered to be useful in studying both the initial and the persisting
      stage of infection in the peritoneum, whence a slow release of bacteria into the
      blood takes place which finally leads to sepsis and septicemia.

PMID- 14976727
TI  - Virulence factors and in vitro adherence of Enterococcus strains to urinary
      catheters.
AB  - The ability to adhere in vitro to urinary catheters and the presence of
      enterococcal virulence factors was determined in 30 Enterococcus urinary isolates
      (12 E. faecalis, 12 E. faecium, 3 E. casseliflavus, 3 E. gallinarum). Silicone,
      siliconized latex and polyvinyl chloride (PVC) were examined by sonication
      quantitative culture technique and scanning electron microscope. As compared to
      E. faecalis and E. faecium, E. casseliflavus and E. gallinarum displayed lower
      adhesion to all synthetic materials. All the tests performed showed higher
      adherence of all tested strains to siliconized latex and silicone than to PVC.
      Biofilmforming ability was observed in 5 E. faecalis but in none of the remaining
      strains. The gene coding enterococcal surface protein (Esp) was detected in 7 E.
      faecalis and 6 E. faecium strains. Gelatinase was found in 1 E. faecalis, 2 E.
      faecium and hemolysins were found in 6 E. faecalis and 1 E. faecium strains. All
      E. casseliflavus and E. gallinarum strainswere negative for these traits.
      Hydrophobic type of cell surface (measured by its affinity for n-hexadecane) was
      shown in a few isolates. Bacterial adherence was not significantly associated
      with the above pathogenic factors.

PMID- 14976728
TI  - Antifungal activity of some bis-5-methylbenzimidazole compounds.
AB  - Twenty bis-5-methylbenzimidazole compounds were evaluated for their in vitro
      antifungal activity against Candida albicans and Candida tropicalis. Except for
      three all compounds exhibited an antifungal activity against these yeasts over a
      range of the minimum inhibitory concentration (MIC) between 25 and 800 mg/L.

PMID- 14976729
TI  - Determination of genetic differences between fluid and nonfluid variants of
      Clavibacter michiganensis subsp. sepedonicus using rep-PCR technique.
AB  - Testing of 23 isolates of Clavibacter michiganensis subsp. sepedonicus for
      analysis by rep-PCR (using BOX, ERIC, REP primer sets) was used for the purpose
      of localization of genetic markers for fluid and/or nonfluid strains. None of the
      primer sets was successful in detecting genetic differences between the isolates
      and no polymorphism was generated.

PMID- 14976730
TI  - The production and application of single-chain antibody fragments.
AB  - This review discusses methods for the single-chain antibody fragment ($cFv)
      generation and scFv expression systems, and describes potential applications of
      scFv in the therapy of viral diseases and cancer, with emphasis on
      intracellularly expressed scFvs (intrabodies), application of scFvs in detection
      and diagnostics, and their use in proteomics.

PMID- 14976731
TI  - Contribution of capsular and lipopolysaccharide antigens to the pathogenesis of
      Klebsiella pneumoniae respiratory tract infection.
AB  - The role of Klebsiella pneumoniae K- and O-polysaccharide antigens was determined
      in a rat model of lobar pneumonia. The induction of experimental infection in
      rats by wild-type strain, and its lipopolysaccharide- and capsular polysaccharide
      deficient mutants was compared. Though the mutant lacking both antigens (K- O-)
      induced infection it could not successfully establish itself in the rat lung. It
      caused only mild infection, as compared to the wild type strain (K+ O+) and the
      strain lacking CPS alone (K- O+). Besides capsular polysaccharide, the
      lipopolysaccharide antigen was shown to be an important factor in pathogenesis of
      K. pneumoniae acute respiratory tract infection.

PMID- 14976732
TI  - [Present status and future aspects of studies on neuronal network formation
      (discussion)].

PMID- 14976733
TI  - [Overview: differentiation and migration of neuronal cells].

PMID- 14976734
TI  - [Cell fate specification during lineage development in the Drosophila embryonic
      central nervous system].

PMID- 14976735
TI  - [Mechanisms for maintenance and differentiation of neural stem cells].

PMID- 14976736
TI  - [The Islet-1 family in subtype specification of motor neurons].

PMID- 14976737
TI  - [Neocortical development].

PMID- 14976738
TI  - [Polarized migration of cerebellar granule cells: the mechanism underlying
      vertical reorientation].

PMID- 14976739
TI  - [Overview: receptors and synapse formation].

PMID- 14976740
TI  - [Molecular mechanisms of central synapse formation and maturation].

PMID- 14976741
TI  - [Actin cytoskeleton of the dendritic spine governs maturation of excitatory
      synapses].

PMID- 14976742
TI  - [Structure-stability-function relationships of dendritic spines].

PMID- 14976743
TI  - [Spine actin dynamics and morphological plasticity].

PMID- 14976744
TI  - [Function and distribution of glutamate receptors in the central synapses].

PMID- 14976745
TI  - [GABAergic neurons revealed in the gene knock-out and knock-in mice].

PMID- 14976746
TI  - [Overview: molecular basis of neural circuit formation].

PMID- 14976747
TI  - [Neurite outgrowth and extracellular matrices].

PMID- 14976748
TI  - [Cellular and molecular mechanisms to achieve diversity of dendritic patterns].

PMID- 14976749
TI  - [Semaphorins and their receptors, neuropilins and plexins, regulate neural
      circuits formation].

PMID- 14976750
TI  - [Guanine nucleotide exchange factors for Rho family GTPases: specific mediators
      for a variety of signals].

PMID- 14976751
TI  - [Rho family GTPases as key regulators for neuronal network formation].

PMID- 14976752
TI  - [Cerebellar circuit development and gene expression].

PMID- 14976753
TI  - [Molecular mechanisms of the layer-specific neural connections in Drosophila].

PMID- 14976754
TI  - [Development of barrels in the rodent somatosensory cortex].

PMID- 14976755
TI  - [Mechanisms for the regional specification in the topographic retinotectal
      projection].

PMID- 14976756
TI  - [Synaptic plasticity and neural circuits: a general view].

PMID- 14976757
TI  - [Roles of chemical mediators in sound sequence discrimination in the auditory
      cortex].

PMID- 14976758
TI  - [Heterosynaptic plasticity in CA3 hippocampus].

PMID- 14976759
TI  - [Age and experience dependence of long-term synaptic modification in visual
      cortex].

PMID- 14976760
TI  - [Synaptic differentiation in the developing cerebellum].

PMID- 14976761
TI  - [Molecular mechanisms of long-term potentiation in hihhocampus].

PMID- 14976762
TI  - [Synaptic plasticity and NMDA-type glutamate receptors].

PMID- 14976763
TI  - [Calcium channel mutations and disorders of synaptic transmission].

PMID- 14976765
TI  - [Pheromonal memory and synaptic plasticity].

PMID- 14976764
TI  - [Synaptic activity-dependent regulation of neuronal gene expression].

PMID- 14976766
TI  - [Fyn and CNR molecules regulate cortical layer formation].

PMID- 14976767
TI  - [Overview: molecular mechanisms for learning and memory].

PMID- 14976768
TI  - [Analysis of neural mechanisms underlying learning behaviors using activity
      dependent gene expressions].

PMID- 14976769
TI  - [Behavioral analysis of transgenic and knockout mice].

PMID- 14976770
TI  - [Molecular genetics on behavioral plasticity in Caenorhabditis elegans:
      thermotaxis mechanism in C. elegans].

PMID- 14976771
TI  - [Molecular genetics on behavioral plasticity in Caenorhabditis elegans:
      mechanisms for associative learning].

PMID- 14976772
TI  - [Genetic regulation of circadian rhythms].

PMID- 14976773
TI  - [Neuronal coding by cell assemblies: to detect in experiments].

PMID- 14976774
TI  - [Overview: neuronal feature extraction and integration].

PMID- 14976775
TI  - [Feature extraction in the auditory nuclei].

PMID- 14976776
TI  - [Generation and function of synchronous oscillations in the retina].

PMID- 14976777
TI  - [Functional organization of segmentally homologous reticulospinal neurons in
      hindbrain].

PMID- 14976778
TI  - [Associative learning: classical eyeblink conditioning with special reference to
      the role of the higher nervous system].

PMID- 14976779
TI  - [50 years old of the Luis Roche Foundation].

PMID- 14976780
TI  - [Biovolume of some centric diatoms from the northeastern continental shelf of
      Venezuela].
AB  - Biovolume variation of twelve centric diatom species from eight natural habitats
      of the northeastem continental shelf of Venezuela were analyzed. Also, the
      morphometric variable that exerts the greatest influence on the biovolume was
      determined. Samples were collected with a net (mesh 36 microns), or with a Niskin
      bottle (5 l) and fixed with neutralized formaldehyde (4%). Water temperature and
      salinity were measured. The species studied were: Detonula sp., Skeletonema
      costatum, Lauderia annulata, Pseudoguinardia recta, Cerataulina pelagica,
      Helicotheca tamesis, Rhizosolenia styliformis, Proboscia alata, Guinardia
      flaccida, G. striata, Dactyliosolen fragilissimus y Leptocylindrus danicus. Forty
      individuals of each species from each locality were isolated and measured with a
      Leitz Wetzlar binocular microscope with an ocular micrometer, magnified 400X. A
      one-way ANOVA showed the existence of highly significant differences (p < 0.001)
      in the biovolume of the species regarded with its locality. These differences
      could be due to: (a) temporal differences in sample collection: (b) the existence
      of populations in different phases of their vital cycles; (c) genetic
      differences; (d) and differences in the physical-chemical environment at each
      locality. The diameter was the morphometric variable exhibiting the largest
      positive correlation (r > or = 0.77, p < 0.001) with biovolume for all species,
      except for H. tamesis. In the latter, the apical axis (or side) exhibited the
      best correlation with biovolume (r = 0.94, p < 0.001). The high correlation
      between the diameter and/or the apical axis with the biovolumen suggests that the
      latter could be predicted from these morphometric variables with great
      reliability in these species.

PMID- 14976781
TI  - [Pollination and pollinators in the vegetation of the coastal plain of Paraguana,
      Falcon State, Venezuela].
AB  - Pollination systems and plant-pollinator dynamics were studied for 51 plant
      species according to life form, vegetation type, and flowering phenology in the
      Paraguana peninsula, Venezuela. A total of 43 species of floral visitors were
      recorded from which only 33 (76.7%) were effective pollinators and ten only
      visitors. Pollinator fauna consisted only of insects. Six pollinating agent
      classes were identified in the area of study. Pollinating bees were the most
      important class (35.1%), followed by butterflies (24.3%) and flies (13.5%). This
      trend was similar for the psamophilous and mangrove vegetation, but pollinating
      wasps were the third in importance in the littoral vegetation. Temporal
      distribution of pollinating agent classes showed a peak during the flowering
      peak, and during the lowest level of rainfall in the locality. Pollination
      systems were mostly polyphilous (62.7%) followed by monophilous (27.4%), and
      oligophilous species (7.8%). This trend was found to be similar for the different
      vegetation types and life forms. In a similar way, pollinator agents were mainly
      polytropic (60.4%), followed by monotropic (24.6%) and oligotropic species
      (14.8%). Plant species/pollinator species ratio was close to one for all
      vegetation types in the Paraguana peninsula. Besides, the average number of
      pollinator species per plant species was 2.2, and the average number of plant
      species pollinated per insect species was 2.7. Plant species/pollinator species
      ratio and the average values of pollinator and plant species indicate a diffuse
      and symmetric relation between pollinator and plant species. These results are
      discussed in the context of the dynamics of pollination.

PMID- 14976783
TI  - [Prevalence of Anaplasma marginale and specific antibodies in new born calves].
AB  - Anaplasma marginale is an intraerythrocytic rickettsia that affects the cattle
      and constitute a constraint for its production. The transplacental transmission
      of A. marginale could be of importance under field conditions, but until now no
      data is available to interpret its relevance in Venezuela. The goal of this work
      was to evaluate both the presence of A. marginale and the antibody response
      against the rickettsia in new born calves. Fourteen calves, one week old, were
      simultaneously bled for parasitological tests, packed cell volume measurement and
      to obtain sera for immunoenzymatic assays. All the animals showed parasitemia
      between seventeen and thirty days old. The antibody IgM and IgG response at this
      time was low. Probably, these calves acquired A. marginale infection through
      transplacental route and a very low level of immunity by the colostrum.

PMID- 14976782
TI  - Priming rapacuronium: a comparison with rocuronium and mivacurium.
AB  - The aim of this study is to present the pharmacodynamics of the priming principle
      using rapacuronium and a comparison with rocuronium and mivacurium. After
      induction, 120 patients were randomly allocated to six similar groups. Groups 1
      and 2 received rapacuronium 1000 micrograms.Kg-1 as a bolus or primed with 100
      micrograms.Kg-1. To groups 3 and 4, rocuronium 400 micrograms.Kg-1 were given as
      a bolus or primed with 60 micrograms.Kg-1, finally mivacurium 100 micrograms.Kg-1
      was used for groups 5 and 6 by bolus or primed with 10 micrograms.Kg-1.
      Neuromuscular function was monitored by electromyography and it was demonstrated
      that time to 80% blockade, is significantly shorter after priming: 137 (bolus) vs
      101 seconds (priming) for rapacuronium, 160 vs 90 for rocuronium and 196 vs 118
      for mivacurium. Onset time was also statistically accelerated by priming: 229
      seconds vs 183, 289 vs 203 and 298 vs 252 respectively. No significant change was
      noticed in maximal blockade and clinical duration due to priming. During early
      onset, only the mivacurium patients showed a statistical difference in train of
      four fade between bolus and priming. In conclusion, priming hasten early and
      maximal effect produced by rapacuronium, rocuronium and mivacurium without any
      change in maximal blockade and clinical duration. Pre-synaptic effect does not
      explain consistently the mode of action of priming.

PMID- 14976784
TI  - [Physicochemical and functional evaluation of pregelatinized and microwaved
      cassava (Manihot esculenta Cranz) starches].
AB  - The aim of this study was to evaluate the effect of two physical modification
      methods, drum-drying pregelatinization and microwave heating (at 25% moisture),
      on some characteristics of cassava starch. The water absorption, solubility and
      swelling power of pregelatinized starch increased considerably between 65 and 90
      degrees C (56 to 86 g water/g starch, 89 to 99% and 63 to 87, respectively),
      while in microwaved starch these indices dropped, in general terms, from 75
      degrees C (5 to 37 g water/g starch, 1 to 37% and 12 to 38 respectively) compared
      to native starch values (10 to 40 g water/g starch, 2 to 40% and 13 to 41,
      respectively). All samples showed a marked breakdown during heating, while the
      pregelatinized starch has the lowest setback values. The morphology of microwaved
      starch was slightly affected, while in the pregelatinized starch all vestige of
      granular integrity disappeared. Of the two methods used, pregelatinization caused
      the most remarkable changes of cassava starch characteristics.

PMID- 14976785
TI  - [Incorporation of prime and tailing starches of Canavalia ensiformis L. and
      Phaseolus lunatus L. in cookies].
AB  - Incorporation into cookies of prime and tailing starches isolated from Phaseolus
      lunatus and Canavalia ensiformis seeds was carried out and compared with those
      elaborated with conventional corn starch (Maizena), which were sensory evaluated
      and assessed for total dietary fiber (TDF), insoluble dietary fiber (IDF) and
      soluble dietary fiber (SDF) contents. Sensory evaluation was carried out using an
      incomplete block design by a non-trained panel of judges. The analysis of
      variance indicated a significant difference (p < 0.05), in the level of
      acceptation, among the different formulations; cookies elaborated with prime
      starches were preferred. Cookies elaborated with the tailing starches and the
      control cookie had similar acceptance. The cookies prepared with tailing starches
      presented TDF, IDF and SDF contents of 9.3, 4.86 and 4.87%, respectively for C.
      ensiformis and of 9.85, 8.75 and 1.10%, for P. lunatus. These contents were
      higher than those found in other cookies. The use of prime and tailing starches
      of Canavalia ensiformis and Phaseolus lunatus may represent an effective
      alternative in manufacturing of fiber-rich bakery products.

PMID- 14976786
TI  - [Molecular identification of bovine enteric calciviruses in Venezuela].
AB  - Caliciviruses are a well-established cause of respiratory, vesicular and
      hemorrhagic diseases in animals. In addition, these viruses are an important
      cause of enteric diseases in humans. Recently, molecular analysis of several
      bovine enteric calicivirus isolates indicated that they are genetically close to
      human enteric calicivirus. To investigate if bovine enteric caliciviruses
      circulate in Venezuela, 129 stool samples collected between 1994 and 2000 were
      assayed by reverse transcription-polymerase chain reaction amplification. The
      presence of calicivirus was confirmed in one of the samples analyzed, collected
      in the Lara State from a healthy calf, 2 months old. Phylogenetic studies based
      on partial RNA polymerase sequences indicated that the Venezuelan isolate
      (Bo/NV/Lara/2000/VE) is most closely related to the genogroup III, genus
      Noroviruses.

PMID- 14976787
TI  - Endocervical curettage. Does it contribute to the management of patients with
      abnormal cervical cytology?
AB  - OBJECTIVE: To conduct a prospective analysis of whether endocervical curettage
      contributes to the management of patients with abnormal cervical cytology. STUDY
      DESIGN: Three hundred four consecutive patients being evaluated for abnormal
      squamous cervical cytology at the University of Virginia underwent routine
      endocervical curettage at the time of diagnostic colposcopy. RESULTS: Among the
      304 patients evaluated colposcopically, the information provided by endocervical
      curettage changed treatment planning in only 13, or 4.27%. In none of these 13
      patients would the omission of endocervical curettage at the time of diagnostic
      colposcopy have resulted in overlooking an occult invasive or microinvasive
      carcinoma. CONCLUSION: This prospective analysis did not find the information
      provided by the routine application of endocervical curettage at the time of
      diagnostic colposcopy to be helpful in the subsequent treatment planning of
      patients undergoing evaluation for cervical intraepithelial disease.

PMID- 14976788
TI  - Abnormal human chorionic gonadotropin levels and normal pregnancy outcomes in the
      ovarian hyperstimulation syndrome.
AB  - OBJECTIVE: To validate whether abnormally rising human chorionic gonadotropin
      (hCG) levels, in the presence of the ovarian hyperstimulation syndrome (OHSS),
      may serve to diagnose abnormal gestation. STUDY DESIGN: In an observational, case
      control study, the rates of hCG rise after treatment with gonadotropins or
      assisted reproductive technologies were compared. Cases consisted of 9 women with
      OHSS. Controls (121 subjects) were matched except that they did not have OHSS.
      The significance of differences in the slope of the hCG rise was determined by t
      testing. RESULTS: The average doubling time for hCG was 50.4 hours for cases and
      38.0 for controls. The slopes of the hCG rise between the groups differed
      significantly (P = .0015). Pregnancy outcomes were normal for all patients.
      CONCLUSION: Abnormally rising hCG levels do not predict poor outcome in
      pregnancies complicated by OHSS and therefore are not helpful in the decision
      making process to diagnose ectopic or otherwise compromised pregnancies.

PMID- 14976789
TI  - Decreasing infectious morbidity in cesarean delivery by changing gloves.
AB  - OBJECTIVE: To assess whether changing the entire surgical team's gloves
      intraoperatively, after delivery of the placenta, would reduce the rate of
      postcesarean wound infection. STUDY DESIGN: Women who underwent cesarean delivery
      were randomized to a group where the surgical team changed the surgical gloves
      after delivery of the placenta or to a control group, where surgical gloves were
      not changed during the cesarean procedure. RESULTS: Ninety-two patients were
      randomized to 2 groups of 46 patients each. The group where the surgical team
      changed their gloves had significantly less serosanguineous drainage 24 hours
      after surgery (3 vs. 8 patients, 8.3% vs. 22.2%, P = .2, RR 2.7, CI 0.7, 12.4)
      and fewer wound infections (2 vs. 9 women, 5.5% vs. 25%, P = .05, RR 4.5, CI
      0.982, 29.8). CONCLUSION: Obstetricians may decrease the number of postcesarean
      wound infections by having the entire team change surgical gloves after delivery
      of the placenta.

PMID- 14976790
TI  - Ethnicity, acculturation and obstetric outcomes. Different risk factor profiles
      in low- and high-acculturation Hispanics and in white non-Hispanics.
AB  - OBJECTIVE: To compare risk factors and birth outcomes among low- and high
      acculturated Hispanics and white non-Hispanics. STUDY DESIGN: Information on
      1,172 women who delivered was collected in a cross-sectional study at a public
      hospital in Phoenix, Arizona. We compared 3 groups: low-(reference group) and
      high-acculturated Hispanics and white non-Hispanics. Acculturation was defined
      within Hispanics by predominant orientation: Latin America (low) or United States
      (high). RESULTS: Prevalence of substance abuse and interpersonal violence was
      highest in the white non-Hispanics when compared to low-acculturated Hispanics,
      and intermediate in the high-acculturation group. Births to women < 17 years old
      were highest in the high-acculturation group. Preterm labor and pregnancy-induced
      hypertension were more common in white non-Hispanics. Sexually transmitted
      disease was more likely in the high-acculturated Hispanic group. Diabetes was
      more common in both comparison groups, high-acculturated and white non-Hispanic.
      CONCLUSION: High-acculturated Hispanics, like high-risk white non-Hispanics, had
      more risk factors and adverse obstetric outcomes than the low-acculturated group.
      The acculturation process may lead to difficulty for Hispanics in the United
      States.

PMID- 14976791
TI  - Role of smoking in low birth weight.
AB  - OBJECTIVE: To assess the role of smoking on low birth weight (LBW). STUDY DESIGN:
      From Massachusetts for 1998, 79,904 birth certificates were reviewed. Birth
      weight, gestational age, plurality and maternal race were analyzed in relation to
      the mother's smoking status during the pregnancy. The etiologic fraction (EF) was
      calculated for smoking and LBW for the group as a whole as well as for various
      subgroups. RESULTS: A total of 11.7% of women acknowledged smoking during
      pregnancy. The overall LBW rate was 6.83%. The relative risk (RR) of LBW among
      smokers was 1.58. For all births the EF for smoking was 6.4% (95% CI: 5.4-7.3).
      For singleton pregnancies it was 10.9% (95% CI: 9.6-12.1) (14% for singleton
      whites and 7.2 for singleton blacks). At term, the EF of smoking on LBW was 13.4%
      (95% CI: 11.5-15.3), with an EF of 16.7% (95% CI: 14.5-18.7) for term singletons
      (21.4% among whites and 14.6% among blacks). Among very LBW infants, smoking
      accounted for 1.7% (95% CI:--0.5-3.8) of the outcome (5.8% among singletons).
      When stratifying for the effect of smoking, the rate of LBW was 6.38% among
      nonsmokers, 9.5% (RR 1.48, 1.38-1.61) among light smokers, 11.67% (RR 1.82, 1.63
      2.05) among moderate smokers and 11.72% (RR 1.84, 1.33-2.54) among heavy smokers.
      Sixty percent of the overall population effect of smoking on LBW was in the
      category of light smokers. CONCLUSION: The amount of LBW attributable to smoking
      was 6.4% in this sample. Among those who smoked, LBW was 58% more likely than
      among nonsmokers, and 60% of the overall population effect of smoking on LBW was
      noted among light smokers.

PMID- 14976792
TI  - Effectiveness and infectious morbidity of outpatient cervical ripening with a
      Foley catheter.
AB  - OBJECTIVE: To assess the effectiveness and infectious morbidity of outpatient
      cervical ripening with a Foley catheter. STUDY DESIGN: Labor inductions utilizing
      a Foley catheter for cervical ripening from January 1994 to October 1999 were
      retrospectively reviewed. The inductions were divided into inpatient and
      outpatient groups. Vaginal delivery rates and infectious morbidity were compared
      between the 2 groups. RESULTS: There were 315 inpatient and 300 outpatient cases.
      The observed differences in vaginal delivery rates and infectious morbidity were
      not clinically or statistically significant. However, there was insufficient
      power to exclude a type II error. The cost savings was $165,000, and there is the
      potential to save $750 per patient with this method. CONCLUSION: Outpatient
      cervical ripening with a Foley catheter is clinically effective, does not result
      in excess infectious morbidity and is more cost effective as compared to
      inpatient cervical ripening.

PMID- 14976793
TI  - Urodynamic comparison of continent and incontinent women with severe uterovaginal
      prolapse.
AB  - OBJECTIVE: To compare the clinical and urodynamic characteristics of continent
      and incontinent women with severe uterovaginal prolapse. STUDY DESIGN: Fifty
      eight consecutive women with stage III or IV pelvic organ prolapse between June
      1998 and December 2001 were enrolled. Each woman had a urinalysis, pelvic
      examination and urodynamic study and answered a urinary questionnaire. They were
      divided into clinically continent (n = 20) and incontinent (n = 38) groups. The
      clinical symptoms and urodynamic results in the 2 groups were compared
      statistically with the chi 2 test, Fisher's exact test and Mann-Whitney U test.
      RESULTS: Incontinent women with severe genital prolapse were more likely to
      report urinary frequency, urgency and nocturia than were continent women (P <
      .05). However, the incidence of voiding hesitancy was significantly higher for
      members of the continent group as compared to the incontinent group (P = .002).
      With respect to urodynamic variables, including detrusor pressure at peak flow,
      maximal urethral closure pressure and pressure transmission ratio, significantly
      higher values occurred in the continent group as compared with the incontinent
      group; they were 38 (range, 12-66) vs. 24 cm H2O (range, 10-49) (P < .01), 84
      (range, 39-117) vs. 63 cm H2O (range, 45-84) (P = .033) and 102% (range, 66-135)
      vs. 66% (range, 14-98) (P = .019), respectively. All other parameters and the
      incidence of bladder outlet obstruction and detrusor instability did not differ
      significantly between the 2 groups (P > .05). CONCLUSION: The results of this
      study suggest that severe uterovaginal prolapse could produce obstructive
      symptoms and prevent or reduce urinary leakage, but whether urethral kinking or
      external urethral compression causes the obstruction remains unclear. More
      studies on different types of isolated pelvic organ prolapse are needed to
      elucidate the mechanism, and specific strategies can be developed to aid
      urogynecologists in their goal of restoring normal anatomy.

PMID- 14976794
TI  - Outcome of IgM- and IgG-seropositive cases of varicella zoster in pregnancy.
AB  - OBJECTIVE: To study the outcome of IgG- and IgM-seropositive cases of varicella
      zoster virus (VZV) in pregnancy. STUDY DESIGN: The VZV immune status of 120
      pregnant women who had been exposed to VZV and did not recall a history of VZV
      infection was determined, and 109 were VZV immune. Eleven women were both IgG and
      IgM seropositive, and the outcomes of their pregnancies were studied. RESULTS:
      Nine of the 11 VZV IgM-, IgG-seropositive pregnant women were asymptomatic,
      without fetal damage. CONCLUSION: The majority of the women were asymptomatic,
      but no statement about the relative risk of being affected by the virus can be
      made.

PMID- 14976795
TI  - Sex hormone patterns and serum retinol concentrations in adolescent girls.
AB  - OBJECTIVE: To describe the pattern and relation of sex serum hormones and retinol
      concentrations over 1 menstrual cycle in adolescent girls living in a resource
      poor setting. STUDY DESIGN: Venous blood samples were collected on alternate days
      of the cycle, and estrogen, progesterone, luteinizing hormone (LH), follicle
      stimulating hormone and serum retinol were measured. A linear random effects
      model was used to examine the relationship between sex hormones and serum
      retinol. RESULTS: Twenty-eight girls were studied. During the follicular phase,
      serum retinol was associated negatively with progesterone and positively with LH.
      In the luteal phase, serum retinol was positively associated with estrogen. Serum
      retinol increased in the follicular phase but not the luteal phase. Sex hormone
      and serum retinol concentrations showed marked individual and day-to-day
      variability. Two girls maintained serum retinol concentrations > 0.7 mumol/L
      throughout the cycle. Six remained at < 0.7 mumol/L, which indicated subclinical
      deficiency. CONCLUSION: This study indicated that in adolescent girls, sex
      hormone patterns correlate significantly with serum retinol, and in vitamin A
      deficient girls this could be important for reproductive function.

PMID- 14976796
TI  - Tuberculosis peritonitis mimicking ovarian cancer in a 20-year-old woman. A case
      report.
AB  - BACKGROUND: Mycobacterium tuberculosis is the most common cause of tuberculosis
      in the world. Since the mid-1980s the United States has seen an increase in the
      incidence of tuberculosis, attributed largely to an increase in patients infected
      with HIV and to the immigration of infected individuals from endemic areas. The
      disease affects mainly the lungs, but about one-third of patients also have
      involvement of other sites. The incidence of peritoneal tuberculosis is low in
      developed countries and is the sixth most common extrapulmonary site.
      Laparoscopic biopsy provides a rapid and definitive diagnosis. When promptly
      diagnosed, tuberculosis is one of the few diffuse peritoneal processes for which
      there is effective therapy with an excellent prognosis. CASE: A 20-year-old woman
      with a diffuse peritoneal process and elevated CA-125, suspected to be secondary
      to ovarian cancer, as diagnosed as having tuberculosis peritonitis. Diagnostic
      laparoscopy was invaluable in establishing the diagnosis. CONCLUSION: Use of CA
      125 for diagnosis of ovarian cancer may lead to misdiagnosis and unnecessary,
      invasive procedures. Suspecting and establishing a diagnosis by laparoscopic
      biopsy may prevent unnecessary laparotomy.

PMID- 14976797
TI  - Enoxaparin for postpartum ovarian vein thrombosis. A case report.
AB  - BACKGROUND: Intravenous heparin is a recognized treatment for ovarian vein
      thrombosis. Although an effective, less cumbersome alternative exists with
      lowmolecular-weight heparins, the literature does not contain reports of their
      use for this condition. We report a case of postpartum ovarian vein thrombosis
      managed with enoxaparin. CASE: A 29-year-old woman, gravida 1, para 1001, was
      readmitted with postpartum endomyometritis. After 5 days of appropriate
      antibiotics, computed tomography of the abdomen/pelvis demonstrated a right
      ovarian vein thrombus. Enoxaparin was initiated, resulting in a rapid clinical
      improvement, and hospital discharge was achieved within 36 hours. CONCLUSION:
      Enoxaparin treatment for avarian vein thrombosis is an alternative to intravenous
      heparin that may permit a shorter hospital stay without the need for coagulation
      profile monitoring.

PMID- 14976798
TI  - Accidental electric shock in pregnancy and antenatal occurrence of maternal deep
      vein thrombosis. A case report.
AB  - BACKGROUND: Even low-voltage electric shock can initiate late vascular
      thromboses. We present the first reported case of antenatal deep vein thrombosis
      (DVT) in a pregnant woman that could be attributed to the electric shock she
      accidentally received several weeks prior to the DVT. CASE: A 19-year-old
      primigravida presented to the office at 29 weeks of gestation with signs and
      symptoms of DVT. A magnetic resonance imaging revealed an occluding thrombus
      involving the entire left common iliac and external iliac vein. She tested
      negative for all the biochemical abnormalities that could lead to a
      hypercoagulable state. Her prior pregnancy course had been unremarkable with the
      exception of an electric shock she had had secondary to touching exposed electric
      wires at home at 22 weeks of gestation. CONCLUSION: Pregnant women exposed to
      electric shock should be carefully monitored for such complications as DVT during
      the weeks following the exposure.

PMID- 14976799
TI  - Solid pseudopapillary pancreatic tumor in pregnancy. A case report.
AB  - BACKGROUND: Solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm,
      occurring predominantly in young African American women. Tumor growth, which is
      typically slow, may be accelerated during pregnancy secondary to the influence of
      progesterone. CASE: We report a rare case of an 8-cm SPT in the head of the
      pancreas presenting as hyperemesis gravidarum during pregnancy. In contrast to
      previous case reports, surgical resection of the tumor at 16 weeks' gestation,
      although successful, did not ameliorate the patient's abdominal pain, nausea or
      vomiting. With intravenous nutritional support, she delivered a healthy infant
      near term. CONCLUSION: SPT may present as hyperemesis gravidarum. Patients with
      refractory hyperemesis gravidarum should be evaluated for thyroid disease,
      gastroesophageal reflux, cholestasis and pancreatitis. If these more common
      etiologies are excluded, then one may consider SPT in the differential diagnosis,
      particularly in African American patients. SPT may grow during pregnancy due to
      progesterone responsiveness. Surgical resection during pregnancy is possible
      without harmful fetal effects but may not correct gastrointestinal dysfunction
      during pregnancy.

PMID- 14976800
TI  - Peritonitis caused by a ruptured, infected mesenteric cyst initially interpreted
      as an ovarian cyst. A case report.
AB  - BACKGROUND: Mesenteric cysts are rare intraabdominal lesions of childhood that
      may vary in presentation from an asymptomatic mass to an acute abdomen. CASE: We
      encountered a rare case of peritonitis caused by a ruptured, infected mesenteric
      cyst of the mesocolon in a female child that had been initially interpreted as a
      ruptured ovarian cyst. CONCLUSION: When confronted with a large unilocular or
      septated echolucent mass in the lower abdomen in female children, gynecologists
      should consider a mesenteric cyst in the differential diagnosis.

PMID- 14976801
TI  - Laparoscopic enucleation of an endometriotic cyst in a renal transplant patient.
      A case report.
AB  - BACKGROUND: Laparoscopic enucleation of an endometriotic cyst in a renal
      transplant patient has not been reported before. CASE: An endometriotic cyst was
      found in the same side as a transplanted kidney. Laparoscopic enucleation of the
      cyst was performed. CONCLUSION: A renal transplant patient with an endometriotic
      cyst can be treated successfully with laparoscopic enucleation.

PMID- 14976802
TI  - [Numerical evaluation of researchers].

PMID- 14976803
TI  - [What is the limit for cancer treatment].

PMID- 14976804
TI  - [Award goes to genome research:Anu Wartovaara receives the Anders Jahre Award for
      young researcher].

PMID- 14976805
TI  - [Diagnostic accuracy of acute appendicitis].

PMID- 14976806
TI  - [Evaluation and treatment of problem behaviors among adolescents].

PMID- 14976807
TI  - [Does an adolescent with behavioral problem can benefit from inpatient
      treatment?].

PMID- 14976808
TI  - [Multifocal motor neuropathy].

PMID- 14976809
TI  - [Inherited urea cycle disorders in Finland].

PMID- 14976810
TI  - [Unexpected surgical complications of duodenal fistulas].

PMID- 14976811
TI  - [Complex partial status epilepticus as a complication from electroconvulsive
      therapy].

PMID- 14976812
TI  - [A young women with hypochromic microcytotic anemia unresponsive to iron
      therapy].

PMID- 14976813
TI  - [Lamotrigine in clozapine treatment-resistant schizophrenia].

PMID- 14976814
TI  - [Long-acting insulin analog, glargine, in the treatment of type 1 diabetes].

PMID- 14976815
TI  - [Elderly patient with acute vomiting].

PMID- 14976816
TI  - Treatment of primary teeth: endodontic therapy or extraction.

PMID- 14976817
TI  - Penetrating trauma-induced orbital floor fracture. Case report.
AB  - Orbital floor fractures are common in midface trauma. While the mechanism which
      produces them is subject to debate, they are acknowledged to be difficult to
      diagnose solely through clinical means. In presenting the case of an orbital blow
      out fracture caused by penetrating trauma, the author describes the successful
      diagnosis and surgical treatment of a "pure" fracture in which no globe trauma
      occurred.

PMID- 14976818
TI  - Addressing the shortage of qualified dental assistants.

PMID- 14976819
TI  - Accreditation and innovation.

PMID- 14976820
TI  - Office of the General Counsel.

PMID- 14976821
TI  - Preparing for the 2004 Georgia General Assembly.

PMID- 14976822
TI  - MAG announces settlement with CIGNA in RICO lawsuit. Settlement represents major
      victory for patients and physicians.

PMID- 14976823
TI  - MAG's Health Policy office coordinates its efforts with public health and other
      community agencies.

PMID- 14976824
TI  - MAG partners with GeorgiaCares. Georgians saved $28 million in health-related
      expenses.

PMID- 14976825
TI  - 2003 House of Delegates.

PMID- 14976826
TI  - Distinguished Service Award. Joseph P. Bailey Jr., M.D.

PMID- 14976827
TI  - Joseph P. Bailey, Jr., M.D. Distinguished Service Award. Walker L. Ray, M.D.

PMID- 14976828
TI  - Community Service Award. Joseph Valentine Morrison Jr., M.D.

PMID- 14976829
TI  - Non-Physician Distinguished Service Award. Donna Glass.

PMID- 14976830
TI  - Donna Glass Non-Physician Distinguished Service Award. Beverly Noller.

PMID- 14976831
TI  - Jack A. Raines, M.D. Humanitarian Award. Goodman B. Espy III, M.D.

PMID- 14976832
TI  - Sports injuries and baby boomers.

PMID- 14976833
TI  - Case of the season: proliferative myositis.

PMID- 14976834
TI  - Epidural steroid injections.
AB  - Epidural steroid injections have a significant role in the treatment of patients
      with low back, neck, and radicular pain. Although these procedures may not
      address the causative lesions, they often shorten the clinical course of the
      disease process, keep patients out of the hospital, and provide symptomatic
      relief that improves quality of life. These procedures are most accurately
      performed with fluoroscopic guidance and major complications are rare. Although
      support for cervical epidural steroid injection is less uniform than that for
      lumbar and caudal injections, a growing body of experience is beginning to
      support its efficacy and safety.

PMID- 14976835
TI  - Selective nerve root blocks.
AB  - Selective nerve root blocks are valuable diagnostic and therapeutic procedures in
      patients with radicular symptoms. Understanding the anatomy, benefits, and risks,
      as well as precise needle placement, are important factors in performing
      successful nerve root blocks. The techniques we describe come from our training
      and ongoing experience. There are other acceptable methods as well.

PMID- 14976836
TI  - Facet joint and sacroiliac joint injection.

PMID- 14976837
TI  - Lumbar discography: an update.
AB  - Discogenic pain most commonly affects the low back, buttocks, and hips and is
      thought to be a byproduct of internal disk degeneration. It is postulated that
      progressive annular breakdown and tearing results in biomechanical and/or
      biochemical stimulation of the pain fibers that reside in the outer one third of
      the annulus. Although multiple imaging modalities, most notably MRI, can show
      morphologic abnormalities of the spine, discography remains the only test that
      provides physiologic information regarding what role a given intervertebral disk
      plays in a patient's symptom complex. The controversy surrounding discography is
      here to stay until more definitive, well-designed studies are performed. In the
      meantime, there are certain things that can help the discographer maximize the
      accuracy of the test: 1. Always try to inject one "normal" disk as a "control
      level." 2. Be alert for factors that are associated with an increased false
      positive rate (abnormal non-anatomic pain maps, a history of chronic pain of
      spinal or nonspinal origin, abnormal psychometric testing, and prior surgery at
      the injected disk level). In these cases, special attention should be directed to
      both the patient's verbal and nonverbal cues during disk injection. 3. Do not
      give any audible clues as to what level is being injected or when the injection
      is starting or finishing. In this regard, we find it very helpful to have one of
      our personnel talk with the patient during this portion of the procedure while
      closely observing the patient for any nonverbal cues regarding their pain
      response. This distraction is preferable to a silent room where the patient is
      intensely focused on what is going on with the injections. We also find that
      music playing during the procedure helps to relax and often distract the patient
      as well. 4. If the results are equivocal at a level (i.e., you are unable to
      determine whether or not the patient's pain response was truly concordant), go on
      to inject another disk level and then come back to reinject more contrast into
      the disk in question. As radiologists, we tend to focus on the technical aspects
      of a procedure and the anatomic/morphologic information it provides. However, it
      cannot be emphasized enough that when performing lumbar discography, the
      assessment of the patient's pain response during the injection is the most
      important component of the procedure, and requires not only technical skills, but
      an understanding of how best to avoid some of the pitfalls that can lead to
      inaccurate results.

PMID- 14976838
TI  - Vertebral augmentation: vertebroplasty and kyphoplasty.

PMID- 14976839
TI  - Diagnostic and therapeutic injections of the foot and ankle.
AB  - Directed injections of the foot and ankle performed under fluoroscopic guidance
      have both considerable diagnostic value and the potential for targeted therapy by
      accurately delivering corticosteroid and/or anesthetic to the source of pain.
      Both large and small joints in the foot and ankle are readily accessed, offering
      precise information to the foot and ankle surgeon who may be contemplating
      arthrodesis or other intervention. In addition to its role in pain management,
      ankle arthrography may be performed in conjunction with MRI or CT, with improved
      evaluation of articular cartilage and capsular abnormalities.

PMID- 14976840
TI  - Ankle tenography: what, how, and why.

PMID- 14976841
TI  - Percutaneous musculoskeletal biopsy.

PMID- 14976842
TI  - Radiofrequency ablation in the musculoskeletal system.

PMID- 14976843
TI  - Ultrasound-guided injections and aspirations of the extremities.

PMID- 14976844
TI  - Dietary fat and stroke: a different story from coronary heart disease.

PMID- 14976845
TI  - Is obesity still a risk factor for patients undergoing coronary surgery?
AB  - Historically, cardiologists and surgeons have considered obesity as a risk factor
      for mortality and morbidity during cardiac surgery. This factor has in fact been
      included in the Parsonnet score, one of the first risk stratification systems.
      This has led to an under-representation of obese patients with severe ischemic
      heart disease in the surgical population. A review of the recent literature seems
      to suggest that obesity is not any longer a risk factor for mortality and
      morbidity following coronary revascularization. Indeed, obesity is not included
      in the EuroSCORE, a more recent risk stratification system. Further evidence
      suggests that the use of off-pump coronary surgery in these patients is
      associated with a reduced in-hospital mortality and morbidity when compared with
      conventional coronary surgery with cardiopulmonary bypass and cardioplegic
      arrest.

PMID- 14976846
TI  - Arrhythmogenic effects of illicit drugs in athletes.
AB  - Cardiac arrhythmias are among the most important causes of non-eligibility to
      sports activities, and may be due to different causes (cardiomyopathies,
      myocarditis, coronary abnormalities, valvular diseases, primary electrical
      disorders, abuse of illicit drugs). The list of illicit drugs banned by the
      International Olympic Committee and yearly updated by the World Anti-Doping
      Agency includes the following classes: stimulants, narcotics, anabolic agents
      (androgenic steroids and others such as beta-2 stimulants), peptide hormones,
      mimetics and analogues, diuretics, agents with an antiestrogenic activity,
      masking agents. Almost all illicit drugs may cause, through a direct or indirect
      arrhythmogenic effect, in the short, medium or long term, a wide range of cardiac
      arrhythmias (focal or reentry type, supraventricular and/or ventricular), lethal
      or not, even in healthy subjects with no previous history of cardiac diseases.
      Therefore, given the widespread abuse of illicit drugs among athletes, in the
      management of arrhythmic athletes the cardiologist should always take into
      consideration the possibility that the arrhythmias be due to the assumption of
      illicit drugs (sometimes more than one type), especially if no signs of cardiac
      diseases are present. On the other hand, in the presence of latent underlying
      arrhythmogenic heart disease including some inherited cardiomyopathies at risk of
      sudden cardiac death, illicit drugs could induce severe cardiac arrhythmic
      effects.

PMID- 14976847
TI  - Immediate and late results of coronary angioplasty in patients with severe left
      ventricular dysfunction.
AB  - BACKGROUND: Severe coronary artery disease in patients with a markedly depressed
      left ventricular function is associated with a poor prognosis. Even though
      coronary angioplasty (PTCA) has been offered as an alternative to bypass surgery,
      the role of PTCA in the treatment of patients with severe left ventricular
      dysfunction has not been well defined. The aim of the present study was to
      evaluate the immediate and long-term results in patients with severe left
      ventricular dysfunction < or = 35% who underwent PTCA. METHODS: One hundred and
      twenty-five patients with a left ventricular ejection fraction < or = 35% who
      underwent PTCA were analyzed. RESULTS: The mean left ventricular ejection
      fraction was 29.7%. Eighty-seven patients (69.6%) had multivessel disease and 41
      (32.8%) had previous coronary artery bypass graft. Intra-aortic balloon pumping
      was used in 12% of cases. Angiographic success was achieved in 96% of patients.
      Complete revascularization was achieved in 56 patients (44.8%). Major
      complications occurred in 4% of the population and 2 patients died (1.6%). During
      the long-term follow-up re-PTCA due to angiographic restenosis was performed in
      41 patients (34%); 12 patients (10.4%) died. The only parameter which
      significantly correlated with death was the presence of an occluded left anterior
      descending coronary artery not recanalized neither with PTCA nor with coronary
      artery bypass graft. CONCLUSIONS: These data suggest that PTCA may be an
      effective treatment for coronary artery disease in patients with left ventricular
      dysfunction and is associated with high procedural success rate and low
      complications; however, the long-term follow-up seems not to be influenced by the
      PTCA procedure.

PMID- 14976848
TI  - Insulin-treated diabetes mellitus and predictors of mid-term clinical outcome
      after percutaneous coronary interventions with stent implantation.
AB  - BACKGROUND: Patients with type II, insulin-dependent diabetes mellitus have a
      high risk of death and repeat revascularization following successful percutaneous
      coronary interventions. The predictors of outcome in such patients after coronary
      stenting have not been clarified. METHODS: We studied 133 consecutive patients
      with type II, insulin-dependent diabetes mellitus who underwent coronary stenting
      from November 1992 to May 2001. The clinical outcome and predictors of major
      adverse cardiac events (MACE; that is death, myocardial infarction, target vessel
      revascularization) at follow-up were assessed. RESULTS: Out of 133 patients, 102
      (76%) had multivessel (> or = 2 vessels) disease. Eight patients (6.0%) had in
      hospital MACE. Clinical follow-up data at 19.5 months (range 6.1-100 months) were
      available for 121 (91%) patients. The MACE rate was 40.5%; 22 patients (18%)
      died, 17 (14%) of a cardiac death; 7 (5.8%) patients had a myocardial infarction,
      and target vessel revascularization was performed in 35 (28.9%) patients. At
      univariate analysis, hypertension (odds ratio-OR 5.5; confidence interval-CI 2.5
      12.3; p < 0.001), hypercholesterolemia (OR 3.7; CI 1.7-8.2; p = 0.001), a prior
      percutaneous coronary intervention (OR 6.6; CI 2.9-15.4; p < 0.001), a prior
      myocardial infarction (OR 3.1; CI 1.5-6.7; p = 0.003) and the stent length (> or
      = 15 mm) (OR 2.7; CI 1.5-4.3; p = 0.008) were related to MACE. At multivariate
      analysis, hypertension (OR 4.1; CI 1.7-9.9; p = 0.002), a prior percutaneous
      coronary intervention (OR 4.8; CI 1.9-12; p = 0.001) and the stent length (OR
      3.0; CI 1.3-7.4; p = 0.01) remained as independent predictors of MACE.
      CONCLUSIONS: Patients with insulin-dependent diabetes mellitus continue to face a
      high mortality and incidence of adverse events after stenting. The occurrence of
      events was related to a history including hypertension, percutaneous coronary
      interventions and to the stent length.

PMID- 14976849
TI  - The interpretation of the electrocardiogram in patients with pulmonary
      hypertension: the need for clinical correlation.
AB  - BACKGROUND: The detection and treatment of pulmonary hypertension have become
      increasingly important for the clinician. While the electrocardiogram is often
      used as a screening tool in patients suspected of having pulmonary hypertension,
      the sensitivity for detecting right ventricular hypertrophy in the era of
      computerized electrocardiogram analysis is highly suspect. The aim of the study
      was to determine the importance of clinical information in providing an
      accurately edited electrocardiographic system. METHODS: The interpretation of the
      electrocardiograms of 64 consecutive symptomatic patients (12 males, 52 females,
      mean age 43 +/- 13 years) with isolated pulmonary hypertension provided by the
      computer program and the cardiologist following editing during routine daily
      reading sessions were reviewed. The reader (blinded cardiologist) was unaware of
      the clinical diagnosis. Subsequently, a cardiologist given clinical information
      regarding age and symptoms, edited the computer interpretation. RESULTS: The
      unblinded cardiologist diagnosed right axis deviation > 90 degrees, right
      ventricular hypertrophy, right ventricular strain, and right atrial enlargement
      in 76.6, 78.1, 71.9 and 20.3% of patients, respectively. In 6 (9.4%) patients,
      the electrocardiogram was normal. The blinded cardiologist and computer program
      diagnosed right ventricular hypertrophy in 43.8 and 39.1% respectively and most
      often characterized right ventricular strain as non-specific or inferior or as
      antero-lateral ischemia. CONCLUSIONS: The electrocardiogram has a high degree of
      sensitivity for the detection of abnormalities in symptomatic patients with
      isolated pulmonary hypertension. Correlation with the clinical parameters is
      essential to optimize the usefulness of the electrocardiogram. Consideration
      should be given to tailoring computerized electrocardiogram interpretative
      software to clinical information.

PMID- 14976850
TI  - Long-term experience with the prenatal diagnosis of cardiac anomalies in high
      risk pregnancies in a tertiary center.
AB  - BACKGROUND: The aim of this study was to analyze the role of the prenatal
      diagnosis of cardiac anomalies in our center. METHODS: The data of 5540 pregnant
      women at risk for congenital heart disease and studied at fetal echocardiography
      between 1984 and 2002, with complete follow-up were retrospectively analyzed.
      RESULTS: There was a progressive gradual increase in the number of cases examined
      per year; 670 fetuses (12% of the population) had congenital heart disease, 6.3%
      of the milder lesions were not detected. A cardiac arrhythmia was diagnosed in
      284 fetuses. Extracardiac and chromosomal anomalies were associated in 23.7 and
      14.6% respectively. Recurrence of congenital heart disease was 4.1%. One hundred
      and seventy-four patients (26%) opted for pregnancy termination; of the 496
      fetuses whose parents decided to continue with pregnancy, 10.1% died in utero,
      33.7% postnatally and 56.2% survived. The post-surgical mortality was 30.4%.
      Negative prognostic factors were associated anomalies, heart failure and complex
      congenital heart disease. Twenty-nine out of 33 fetuses with persistent
      tachyarrhythmias treated in utero survived; fetuses with complex and isolated
      atrioventricular block had a 75 and 11.1% mortality. CONCLUSIONS: Prenatal
      diagnosis was useful in the management of pregnancy and a planned birth and was
      life-saving in case of tachyarrhythmia.

PMID- 14976851
TI  - Myectomy-myotomy associated with aortic valve replacement for aortic stenosis:
      effects on left ventricular mass regression.
AB  - BACKGROUND: Left ventricular outflow tract dynamic obstruction may develop after
      aortic valve replacement for aortic stenosis with a higher mortality and
      morbidity and may persist until left ventricular mass regression occurs. The aim
      of this study was to ascertain the effects of myectomy-myotomy on the left
      ventricular mass and mean wall thickness regression and on left ventricular mass
      normalization at least 1 year postoperatively. METHODS: A total of 162 patients
      including 71 with myectomy-myotomy (group I) and 91 without (group II) were
      studied at pre- and postoperative echocardiography. RESULTS: The relative left
      ventricular regression, after adjustment by ANCOVA analysis, was significantly
      greater in group I than in group II (-24.6 +/- 14.7 and -16.8 +/- 17.8%, p =
      0.004) and the absolute mean wall thickness regression was greater in group I
      than in group II (-1.6 +/- 1.3 vs -1.1 +/- 1.6 mm, p = 0.019). Multivariable
      analysis showed myectomy-myotomy as an independent predictor of left ventricular
      mass regression. CONCLUSIONS: Myectomy-myotomy may improve left ventricular mass
      regression after aortic valve replacement for pure aortic stenosis.

PMID- 14976852
TI  - Surgical treatment of atrial fibrillation in the beating heart: a novel approach.
AB  - Up to 50% of patients undergoing mitral valve surgery have concomitant atrial
      fibrillation. An epicardial approach may offer the benefit of reducing the aortic
      cross-clamping time and avoiding an undue left atriotomy. During the last year we
      have been developing a simple technique to reproduce epicardially the same lesion
      pattern we had previously achieved endocardially. Two patients with chronic
      atrial fibrillation received atrial ablation using a microwave energy probe (Flex
      10, AFx Inc., Fremont, CA, USA) immediately before undergoing a concomitant
      cardiac procedure. The procedure is relatively quick to perform and with
      appropriate care can be conducted with a low risk of perioperative adverse
      events.

PMID- 14976853
TI  - Surgical experience with "waistcoat aortoplasty": an update.
AB  - BACKGROUND: Some patients with primary aortic valve disease can present with an
      associated asymmetrical dilation of the aortic root and/or ascending aorta
      without diffuse congenital aortic wall defects. In such cases "waistcoat
      aortoplasty" has been performed: the present study updates the report of the
      results of 73 procedures. METHODS: Seventy-three patients underwent aortic valve
      replacement and waistcoat aortoplasty. Sinus dilation was repaired by plicating
      the subcoronary redundant aortic wall using the anchoring sutures of the valve
      prosthesis. Through a triangular resection the most diseased segment of the
      aortic wall was removed and the aorta was reconstructed with a double layer
      technique. Thus autologous reinforcement of the convex right postero-lateral wall
      and stress reduction on the aortotomy suture line were both achieved.
      Echocardiography was performed preoperatively, postoperatively and then every 6
      months. The paired Student's t-test was employed to evaluate the significance of
      the diameter variations. RESULTS: The procedure was performed with no hospital
      mortality and a low postoperative morbidity. The post-reduction diameters at the
      sinuses, sinotubular junction and ascending aorta were significantly smaller than
      the preoperative ones (p < 0.001). During an echocardiographic follow-up of 39.2
      +/- 12.5 months (range 14-58 months), no significant increase in the root (p =
      0.18), sinotubular junction (p = 0.22), and ascending diameter (p = 0.34) was
      observed. CONCLUSIONS: Although further studies are needed to confirm these
      results in the longer term, waistcoat aortoplasty should be taken into
      consideration in case of asymmetric ascending dilation secondary to aortic valve
      disease-related medial degeneration.

PMID- 14976854
TI  - Coronary artery disease in young patients with systemic lupus erythematosus: two
      case reports.
AB  - The cardiovascular system is often involved during systemic lupus erythematosus
      (SLE), but only few studies have documented myocardial ischemia and myocardial
      infarction in young patients. We observed 2 cases of coronary artery disease in
      young patients with SLE and different clinical presentations. In the first case,
      a 26-year-old woman, with SLE diagnosed at the age of 12 years, was evaluated for
      angina (CCS class II). Myocardial scintigraphy revealed a clear reversible
      thallium-201 apical perfusion defect. During the following 5 years worsening
      effort angina led to coronary angiography which revealed the presence of a
      complete obstruction of the left anterior descending coronary artery (LAD)
      treated with surgical myocardial revascularization (internal mammary artery
      implantation on the LAD). The second patient had myopericarditis and an acute
      myocardial infarction 1 year before coming to our observation. Coronary
      angiography revealed the presence of 100% obstruction of the LAD. On this basis,
      a diagnosis of SLE was made. Our data constitute two relevant examples of
      coronary artery disease with different clinical presentation in young SLE
      patients.

PMID- 14976855
TI  - A complex triple valve repair in a young rheumatic patient.
AB  - We report a case of a 22-year-old Ethiopian female presenting with multiple
      rheumatic valve disease. She was admitted to hospital because of dyspnea at rest.
      She underwent open mitral commissurotomy associated with splitting of the postero
      medial papillary muscle, aortic right-coronary-left coronary commissural
      resuspension with resection of fibrous tissue from the free-edge cusps and open
      tricuspid commissurotomy of all three commissures completed with chordal
      shortening of the anterior leaflet. The postoperative course was uneventful. The
      patient was asymptomatic without recurrence of symptoms at 2 months.
      Echocardiography confirmed the satisfactory outcome of the multiple repair with
      no residual insufficiency. Multiple repair is advisable for patients living in
      many areas of the Third World, where the safety of long-term anticoagulation
      cannot be assured.

PMID- 14976856
TI  - Traumatic tricuspid valve rupture treated by minimally invasive thoracotomy.
AB  - Isolated valvular lesions consequent to non-penetrating trauma are rare. We
      present a case of a traumatic tricuspid valve rupture in a 51-year-old woman
      seriously involved in a motor vehicle accident 20 years earlier. She underwent
      tricuspid valve replacement performed via a minimally invasive thoracotomy in the
      right fourth intercostal space. The advantages of minimally invasive thoracotomy
      are discussed.

PMID- 14976857
TI  - Transient platypnea-orthodeoxia-like syndrome induced by propafenone overdose in
      a young woman with Ebstein's anomaly.
AB  - In this report we describe the case of a 37-year-old white woman with Ebstein's
      anomaly, who developed a rare syndrome called platypnea-orthodeoxia,
      characterized by massive right-to-left interatrial shunting with transient
      profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale
      occurred in the presence of a normal pulmonary artery pressure, and was probably
      precipitated by a propafenone overdose. This drug caused biventricular
      dysfunction, due to its negative inotropic effect, and hypotension, due to its
      peripheral vasodilatory effect. These effects gave rise to an increase in the
      right atrial pressure and a decrease in the left one with a consequent stretching
      of the foramen ovale and the creation of massive right-to-left shunting. In our
      case this interatrial shunt was very accurately detected at bubble contrast
      echocardiography.

PMID- 14976858
TI  - Management of patients with persistent chest pain and ST-segment elevation during
      5-fluorouracil treatment: report about two cases.
AB  - 5-Fluorouracil, a widely used drug in cancer treatment, is known to have
      cardiotoxic effects: chest pain with ECG changes, arrhythmias, arterial
      hypertension or hypotension, myocardial infarction, cardiogenic shock and sudden
      death have been described in the literature. Coronary artery vasospasm is the
      pathogenetic mechanism hypothesized in most cases, but mechanisms other than
      myocardial ischemia had been advocated in some patients. The approach to the
      patient with persistent chest pain, despite therapy and persistent ST-segment
      elevation mimicking an acute myocardial infarction, has not been well addressed,
      and the appropriate diagnostic and therapeutic pathways have not yet been
      defined. We present our experience regarding 2 patients treated with 5
      fluorouracil and referred to our coronary care unit because of prolonged chest
      pain (in one case with clinical evidence of hemodynamic impairment) and
      persistent ST-segment elevation, in whom an acute myocardial infarction was
      suspected. One patient was treated with systemic fibrinolysis, and coronary
      angiography was performed 6 days later; the other was submitted to urgent
      coronary angiography shortly after admission. In both cases the ECG and
      echocardiographic abnormalities were transient and normalized within a few days,
      the serum markers of myocardial necrosis were persistently in the normal range
      and the coronary artery trees were normal. The diagnostic and therapeutic
      approach to patients with this unusual clinical presentation is also discussed.

PMID- 14976859
TI  - Type IV dual left anterior descending coronary artery evaluated using multislice
      computed tomography: anatomy of a rare coronary anomaly.

PMID- 14976860
TI  - [Infective endocarditis: clinical echocardiography].
AB  - Infective endocarditis is a rare but serious disease. The incidence in western
      countries is 1.7-6.2 cases/100,000 per year. The mortality rate today is 20-40%.
      The Duke University incorporates echocardiographic findings as one of the major
      criteria in the diagnosis of infective endocarditis. In case of suspected
      infective endocarditis, echocardiography is used to: 1) detect and characterize
      endocarditic vegetations; 2) detect complications; 3) conduct follow-up after
      treatment. Sensitivity for detection of vegetations in native-valve endocarditis
      is < 65% by transthoracic echocardiography, whereas it is 82-100% by
      transesophageal echocardiography; in infective endocarditis on prosthetic valves,
      sensitivity is 16-36 and 82-96%, respectively. Echocardiographic studies have
      demonstrated that highly mobile vegetations with a diameter of > 10 mm are more
      likely to cause complications (embolism, heart failure, need for surgery, and
      death). Another important advantage offered by echocardiography is the ability to
      accurately detect cardiac complications of infective endocarditis: valvular
      regurgitation, valve rupture, periannular abscess, prosthetic dehiscence, rupture
      of cardiac fibrosa, septal abscess, hemopericardium, and myocardial infarction.
      The sensitivity of transthoracic echocardiography for the detection of
      periannular abscess is 28% whereas that of transesophageal echocardiography is
      87%. Finally, echocardiography has an invaluable role in indicating if surgery is
      required in cases of infective endocarditis with severe complications.

PMID- 14976861
TI  - [What is new about stroke prevention?].
AB  - More than 186,000 strokes occur every year in Italy, responsible for 10-12% of
      total mortality. Despite the reduction in mortality and disability, the incidence
      of stroke is persistently high and mortality within the first month is about 30%;
      furthermore, the severe residual disability is about 40% in survivors. Large
      clinical outcome trials have defined the strict correlation between stroke and
      systolic and diastolic hypertension, and several meta-analyses and intervention
      studies showed that reduction of blood pressure, independently of the drug used
      (diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme
      inhibitors), decreases significantly (> or = 30%) stroke mortality and morbidity
      in hypertensives. Despite numerous and effective antihypertensive drugs, stroke
      mortality and morbidity in hypertensive subjects remain persistently higher than
      in normotensive ones. Two recent clinical studies confirmed the great efficacy of
      angiotensin II antagonists in reducing stroke relative risk in hypertensive
      patients at elevated cardiovascular risk. The LIFE study demonstrated that an
      active treatment is superior to another one in reducing the prefixed endpoint.
      This important result has conferred great expectancy on angiotensin II
      antagonists and on their possible "class effect". Considering the recent
      intervention trials and the correct interpretation of the evidence-based
      medicine, we should not consider all principles as belonging to the same
      category, equally effective in the prevention of cardiovascular risk. The concept
      of "class effect" has not a real scientific value and cannot replace the
      experimental results of clinical studies which represent the only bench test for
      the efficacy of a drug.

PMID- 14976862
TI  - [Is early discharge possible in patients with uncomplicated heart failure? Cost
      efficacy analysis].
AB  - BACKGROUND: Heart failure is a common indication for admission to the hospital
      among old adults. The hospital stay for uncomplicated heart failure is often too
      long. We hypothesized that a rapid optimization of care and a guideline-based
      approach would allow an early discharge of patients, still maintaining a greater
      quality and efficiency of care. METHODS: We conducted a randomized trial of the
      effect of a guideline-based intervention on rates of readmission within 90 days
      of hospital discharge and costs of care for patients who were hospitalized for
      heart failure and discharged after 4 days of stay. The intervention consisted of
      early echocardiography, aggressive diuretic therapy, comprehensive education of
      the patient and family, a prescribed diet, and intensive application of the
      guidelines' recommendations on pharmacological therapy. Fifty early-discharged
      patients were compared to 50 concurrent normally-discharged patients. RESULTS:
      Average length of stays during baseline admissions was shorter for early
      discharged patients respect to controls (3.9 +/- 0.8 vs 7.0 +/- 1.9 days, p <
      0.001). At discharge, when compared with control patients, early-discharged
      patients were similarly prescribed and/or were taking similar dosages of ACE
      inhibitors (84 vs 80% and 17 vs 15 mg/die, p = NS), beta-blockers (64 vs 56% and
      14 vs 16 mg/die, p = NS), spironolactone (86 vs 70% and 36 vs 32 mg/die, p = NS),
      digoxin (74 vs 70% and 0.18 vs 0.15 mg/die, p = NS), and losartan (8 vs 6% and 50
      mg/die for both groups, p = NS). Hospital readmission rates and days of stay were
      similar between groups (6 vs 8% and 18 vs 26 days, respectively for study and
      control patients), whilst the overall costs of care were lower for early
      discharged patients (289 vs 449 [symbol: see text] per patient per month), due to
      the shorter length of stay at baseline. Survival for 90 days was achieved in 47
      patients both in the study and control groups (p = NS). CONCLUSIONS: Our study
      showed that patients admitted for heart failure may be safely discharged 4 days
      after admission. An in-hospital guideline-based management of patients allows
      relevant cost savings, reducing hospital readmission for heart failure.

PMID- 14976863
TI  - [Surgical myocardial revascularization in patients over and under 70 years of
      age: results and prognostic factors].
AB  - BACKGROUND: The increase in mean age has made older patients candidates to
      myocardial revascularization. This study is focused to evaluate hospital
      mortality and major postoperative complications in two groups of patients < or =
      70 or > 70 years. The possible confounder effect of other important risk factors
      has been studied in multivariate models. METHODS: From January 1 to December 31,
      2002, 228 patients < or = 70 years (group A) and 116 patients > 70 years (group
      B) underwent isolated myocardial revascularization. We analyzed the incidence of
      hospital mortality, cardiac failure, postoperative bleeding, major arrhythmias,
      atrial fibrillation, respiratory failure, renal failure, sternal infection,
      stroke, transient ischemic attack, total neurological complications, and number
      of patients with at least one of these complications. Univariate statistical
      analysis was used to compare this two groups and multivariate analysis to adjust
      for four known important risk factors, i.e. sex, diabetes, ejection fraction <
      0.40, and off-pump surgical technique. RESULTS: Hospital mortality was
      statistically higher in group B than in group A (7.8 vs 1.7%, p < 0.05). The
      incidence of cardiac failure, although higher in group B, was not statistically
      significant. Multivariate analysis confirmed low ejection fraction as the only
      statistical risk factor for low cardiac output (p < 0.05). Atrial fibrillation
      was statistically higher in group B (p < 0.05). No difference was found for all
      other complications considered. Age, low ejection fraction and the use of
      cardiocirculatory bypass at multivariate analysis were statistically significant
      risk factors for the incidence of at least one postoperative event. CONCLUSIONS:
      Myocardial revascularization in patients > 70 years has a higher mortality and
      morbidity. At multivariate analysis, low ejection fraction is also confirmed as a
      significant risk factor for low cardiac output and total morbidity. At the same
      time, the technical option of "beating heart" myocardial revascularization seems
      to achieve better results and probably it should be used more extensively in this
      group of patients.

PMID- 14976864
TI  - [Cardiologists and malpractice: the right time to face a pressing problem].

PMID- 14976865
TI  - Breastfeeding laws, needed or not?

PMID- 14976866
TI  - Kansas State Board of Nursing position statement. Administration of i.v.
      "conscious sedation" (moderate sedation/analegesia) by the registered
      professional nurse.

PMID- 14976867
TI  - Interpretive guidelines for standards of care determinations for Kansas risk
      management law implementation.

PMID- 14976868
TI  - Birth of the domains Bacteria, Archaea and Eucarya and of major taxa within them:
      a hypothesis.
AB  - A hypothesis to explain how the birth of the Bacteria, Archaea and Eucarya
      domains and of major taxa within them took place is presented. It is proposed
      that the birth of each domain was an independent event consisting in the genetic
      isolation of a particular cell from a very diverse pool of "primitive cells".
      Cells within this pool have a dynamic pattern of cell fusion followed by mostly
      illegitimate DNA recombination. It is postulated that genetic isolation was
      achieved: a) by evolution of the peptidoglycan layer in Bacteria, b) by evolution
      of a glycoproteic cell wall in Archaea, and c) by evolution of the nuclear
      membrane in Eucarya. It is also postulated that, within each domain, branching
      was a consequence of sporadic events of fusion between two cells of different
      phylogenetic lineages, followed by mostly illegitimate DNA recombination and cell
      wall regeneration. The two fusing cells may have belonged to the same domain, to
      different domains or even one may have belonged to one of the domains and the
      other to the pool of "primitive cells". In this last case, new complex
      phenotypes, previously absent from all the domains, were suddenly introduced in
      one of them (e.g.: photosynthesis in Bacteria, methanogenesis in Archaea). A
      corollary of this theory is that genes should have a phylogenetic tree with
      defined nodes while organisms are characterized by discontinuities instead of
      nodes.

PMID- 14976869
TI  - [Group B Streptococcus carriers among pregnant women].
AB  - Streptococcus agalactiae--group B streptococci (GBS)--is a main cause of severe
      neonatal infections with a high mortality rate. The detection of pregnant GBS
      carriers (5-35%) allows intrapartum administration of antibiotic prophylaxis to
      these women and prevents perinatal infection. We studied the prevalence of GBS in
      259 patients between 28 and 37 weeks gestation from April 2000 to March 2002. The
      anorectum (AR) and vaginal introitus swabs (VI) were cultured in selective Todd
      Hewitt broth containing colistin (10 micrograms/ml) and nalidixic acid (15
      micrograms/ml) while vaginal swabs (VFS) were cultured following conventional
      methods. A total of 47 strains of EGB were isolated from 259 patients (18.15%).
      The prevalence in different samples were: 5.40% in VFS, 13.51% in VI, 11.58% in
      AR and 17.76% in VI + AR (reference method). The isolates were tested against
      penicillin, ceftriaxone, erythromycin, clindamycin, vancomycin, gentamicin and
      streptomycin to determine the minimum inhibitory concentration. The resistance
      phenotypes of erythromycin-resistant GBS were determined by the double-disk test.
      All strains were susceptible to penicillin, ceftriaxone and vancomycin, only one
      strain was erythromycin and clindamycin resistant by IMLSB mechanism. None of the
      isolated strains had a high resistant level to aminoglycosides. The sensitivity
      of cultures increased when selective broths were used as the primary detection
      method.

PMID- 14976870
TI  - [Evaluation of a colorimetric method for studying the interaction between
      microorganisms and intestinal epithelial cells].
AB  - The aim of the present study was to gain further insight on the reliability of
      the colorimetric determination of the activity of bacterial nitrate reductase to
      evaluate bacterial concentrations and interaction between microorganisms and
      enterocyte-like cells. Nitrite produced after incubation of the samples with a
      nitrate-formate solution was determined with a diazotization reaction with
      sulphanilic acid and N-naphthyl-ethylene-diamonium dichloride. Cell association
      assays were performed with differentiated Caco-2 cells. A biphasic relationship
      was found between nitrite concentration and bacterial densities. This behavior
      seems to be due to the sigmoideal character of the kinetics of nitrate reduction.
      Association to Caco-2 cells was strongly strain dependent being Staphylococcus
      aureus ATCC 25923 the strain showing the highest values of association. For some
      strains, percentages of association calculated on the basis of the colorimetric
      assay were significantly higher than those calculated in terms of viable counts.
      Bacterial association with enterocyte-like cells can be evaluated by measures of
      the activity of bacterial nitrate reductase provided that the biphasic
      relationship between bacterial and nitrite concentrations is taken into account
      for the calculations. Results presented in this paper show the applicability of
      the colorimetric method to assess the amount of microorganisms associated to
      human enterocytes in culture.

PMID- 14976871
TI  - [Characterization of rhizobia causing nodules on leguminous trees native to
      Uruguay using the rep-PCR technique].
AB  - Methods for identifying and following microorganisms in the environment such as
      soils, water and plant association have been highly developed in recent years. In
      this study, we used rep-PCR for the characterization of Rhizobium bacteria
      isolated from legume trees native of Uruguay which permitted to follow them in
      plant inoculation assays. Among the primers used, ERIC and BOX1AR, the latter
      allowed the differentiation of isolates from different legumes and the finding of
      a high level of homology among rhizobia that nodulate the same legume species.
      Besides, it demonstrated that the profiles of the isolates recovered from nodules
      of Acacia caven, were identical to the ones used as inoculants; this confirmed
      the efficiency of these methods to follow these diazotrophs in the environment.

PMID- 14976872
TI  - [Optimization of the conditions for electroporation and the addition nisin for
      Pseudomonas aeruginosa inhibition].
AB  - A mathematical approach was applied in order to optimize the effect of
      electroporation by application of pulsed electric fields (PEF) and nisin addition
      on the inhibition of a strain of Pseudomonas aeruginosa isolated from river
      sediments. This strain showed to be highly resistant to nisin as only two log
      cycles reduction of viable cells were obtained in the presence of 84,000 IU/ml
      nisin. But when a combination of bacteriocin and selected PEF treatment
      conditions were applied, 4.4-decimal log cycle reduction could be achieved. PEF
      and nisin interaction seems to be complex, as at lower electric field intensities
      (i.e., 5 kV/cm) an increment in the number of pulses applied clearly induced a
      lower inhibitory effect of nisin. At higher PEF intensities (i.e., 11 kV/cm), the
      inhibitory effect of nisin increased with the number of pulses applied. Results
      overall, the obtained indicate the possibility of combining PEF and nisin
      treatments in order to improve the inhibition of resistant microorganisms. The
      Doehlert experimental design and surface response methodology was an interesting
      tool to obtain or predict the optimal combination of the stress factors applied.

PMID- 14976873
TI  - [Prevalence of cervical infection by human papilloma virus (HPV) in the Caucasian
      and Guarani populations residing in the province of Misiones, Argentina].
AB  - A genital infection with human papillomavirus (HPV) of a high risk type is
      necessary for the development of cervical carcinoma. HPV viral distribution among
      diverse world populations is not homogeneous, viral reservoirs having been
      detected in particular regions that can interact when humans engage in active
      contacts. Such viral dynamics alters the population cervical cancer relative
      risk, particularly when the prevalence of HPV oncogenic risk types is high. We
      have compared women exposed to different social, cultural and environmental
      conditions regarding cervical HPV infection, analyzing two populations from
      Misiones, Argentina: White urban women and--Guarani indian women living in the
      rain forest. Demographic, clinical and sexual behavior data were collected and
      cytological, colposcopical and virological analysis performed. Detection and
      genotypification of HPV was performed by PCR-RFLP. The prevalence for generic HPV
      infection found was high in both populations, urban women: 43%, Guarani indians:
      60%, with a statistically significant difference. These values were positively
      associated to age of first intercourse, number of male partners and smoking
      history. HPV type-specific prevalences showed a relative homogeneity between
      populations when the main representatives of the high risk (16 and 18: 23%) and
      low risk (6 y 11: 12%) types were grouped together. However, the presence of
      other viral types was notoriously different, representing only 9% in urban women
      and 29% in Guarani indians with particularly high risk HPV types (33, 35, 39, 45,
      51, 52, 58, 67, 68). This situation might be of importance for future viral
      dynamics, phylogenetic and vaccine formulation studies.

PMID- 14976874
TI  - Susceptibility of Candida species to fluconazole assayed by a disk diffusion
      method with automated reading versus a microdilution method.
AB  - In vitro susceptibilities of 290 isolates of Candida spp to fluconazole were
      evaluated by a new NCCLS M44-P agar disk diffusion method that was read and
      interpreted automatically by the BIOMIC image-analysis plate reader system. Disk
      test results were compared to results obtained by a modified NCCLS M27-A broth
      microdilution method using RPMI-1640 supplemented with 2% dextrose. Overall
      agreement between both methods was 90.0%. Category agreement between the broth
      and disk test results for susceptible, susceptible dose-dependent and resistant
      disk results were 99.6%, 19.05% and 52.17%, respectively. No very major
      discrepancies, 1.03% major discrepancies, and 8.97% minor discrepancies were
      observed between results of the two test methods. This analysis suggests that
      results from both methods correlate highly for Candida strains susceptible to
      fluconazole. The lower agreement between the two methods for resistant and
      susceptible dose-dependent isolates was due to strains near or on that
      breakpoint, different media (Mueller-Hinton vs RPMI), agar vs broth, 80% vs 50%
      endpoints, and trailing growth near the endpoints.

PMID- 14976875
TI  - [Degradation of pine needles by Stereum hirsutum].
AB  - Pine-needle degradation by Stereum hirsutum was studied under conditions of solid
      state fermentation with the aim of accelerating its decomposition, avoiding the
      accumulation in situ and in view of the possible utilization of the residual
      organic matter. Three experimental systems were tested: pine needles alone and
      with the addition of either a nitrogen source or barley grain. Determinations
      were made at 14 and 28 days of incubation. All treatments showed substrate
      degradation. The addition of a nitrogen source raised enzymatic activities
      measured but not the degree of degradation. Grain addition resulted in higher
      biomass, enzyme activities, sugar accumulation and degradation of the substrate.
      Fungal biomass estimated as N-acetyl glucosamine allowed calculation of the
      actual degradation of the substrate, that reached 19% at 28 d of culture without
      additions and 44% at 14 d in pine-needles with grain.

PMID- 14976876
TI  - [Monitoring of a HACCP (Hazard Analysis Critical Control Point) plan for Listeria
      monocytogenes control].
AB  - The monitoring of a HACCP (Hazard Analysis Critical Control Point) plan for the
      Listeria monocytogenes control in the cooked and frozen meat section of a thermo
      processing meat plant was evaluated. Seventy "non-product-contact" surface
      samples and fourteen finished product samples were examined. Thirty eight
      positive sites for the presence of Listeria sp. were obtained. Twenty-two
      isolates were identified as L. monocytogenes, two as L. seeligeri and fourteen as
      L. innocua. Non isolates were obtained from finished product samples. The
      detection of L. monocytogenes in cooked and frozen meat section environment
      showed the need for the HACCP plan to eliminate or prevent product contamination
      in the post-thermal step.

PMID- 14976877
TI  - [The guideline for further enforcement of the integration of Chinese and Western
      medicine].

PMID- 14976878
TI  - [Emphasis on evidence research, to facilitate integrative Chinese and Western
      medicine studies in liver disease].

PMID- 14976879
TI  - [About non-alcoholic lipoidal liver disease].

PMID- 14976880
TI  - [To promote further study on treatment of lipoidal liver diseases with
      traditional Chinese medicine].

PMID- 14976881
TI  - [Clinical study on treatment of alcoholic liver disease by qinggan huoxue
      recipe].
AB  - OBJECTIVE: To study the effect of Qinggan Huoxue recipe (QGHXR) in treating
      alcoholic liver disease (ALD). METHODS: By adopting the multi-centered,
      randomized and controlled method, the patients were divided in to the QGHXR group
      (60 patients) treated orally by QGHXR, the XCHG group (30 patients) treated
      orally by Xiaochaihu granule and the control group (30 patients) treated orally
      by conventional therapy such as glucurolactone, vitamin C. The changes in
      symptoms, signs, liver function, blood lipid, liver fibrosis markers, cytokines,
      lipid superoxidation parameters and B-untrasonographic figure after treatment of
      the two groups were observed. RESULTS: The total therapeutic efficacy of QGHXR,
      improvements in anorexia, nausea, vomiting and jaundice as well as effect in
      reducing blood levels of alanine transaminase (ALT), aspartate aminotransferase
      (AST) and triglyceride (TG) were superior in the QGHXR group to those in the
      other two groups (P < 0.01), and the effect in decreasing gamma-glutamyl
      transferase (GGT) and very low-density lipoprotein (VLDL) in the QGHXR group was
      more significant than that in the control group (P < 0.01). QGHXR also showed
      effects in lowering levels of liver fibrosis markers and cytokines, alleviating
      the anti-lipid superoxidation damage in liver, and could markedly improve the
      degree of fatty liver. CONCLUSION: QGHXR shows obvious therapeutic effect in
      treating ALD, the mechanism could possibly be related with its effects in
      antagonizing lipid superoxidation, stabilizing hepatic cell membrane, adjusting
      the lipid metabolic disturbance of liver, regulating immune function, anti-liver
      fibrosis and promoting the intrahepatic metabolism of alcohol.

PMID- 14976882
TI  - [Clinical study on treatment of liver fibrosis by different dosages of Salvia
      injection].
AB  - OBJECTIVE: To find the optimal dosage of Salvia injection in treating chronic
      hepatitis B caused liver fibrosis. METHODS: Sixty-four patients, whose diagnosis
      was confirmed as chronic hepatitis B caused liver fibrosis and differentiated by
      TCM typing as blood stasis blocking Collaterals type, were selected and randomly
      divided by lottery method into the large, middle and small dose of SI treated
      groups and the control group. All the patients were treated with modified Gexia
      Zhuyu Decoction, to the patients in the SI groups, 24 ml, 16 ml and 8 ml of SI
      were additionally administered by intravenous dripping respectively. The
      therapeutic course was 45 days. The clinical symptoms and signs; liver functional
      indexes as alanine transaminase (ALT), aspartate aminotransferase (AST) and
      albumin (ALB); and liver fibrosis indexes as procollagen type III (PC-III),
      collagen type IV (C-IV) and hyaluronic acid (HA), were measured before and after
      treatment. RESULTS: Different dosages of SI all could improve the clinical
      symptoms, and lower levels of ALT, AST, HA, PC-III and C-IV. Treatment of large
      dosage SI showed the best efficacy, superior to that of middle and small dosage
      SI, but no significant difference was found between the efficacy of the latter
      two. CONCLUSION: Anti-liver fibrosis effect of large dosage SI is better than
      that of middle or small dosage SI.

PMID- 14976883
TI  - [Effect of dachengqi granule on human gastrointestinal motility].
AB  - OBJECTIVE: To study the therapeutic effect and mechanism of Dachengqi granule
      (DCQG) on some digestive motility disturbed diseases. METHODS:
      Gastroduodenojejunal manometry, electrogastrography (EGG), RIA of motilin and
      orocecal transit time test were applied to directly observe the effect of DCQG on
      human gastrointestinal motility. RESULTS: DCQG could significantly improve the
      postoperational EGG disorder, elevate the amplitude and time of migrating motor
      complex (MMC) phase III, prevent gastrointestinal reversed peristalsis, increase
      the blood level of motilin, decrease the orocecal transit time, and promote the
      recovery of gastrointestinal motility. CONCLUSION: DCQG is an effective digestive
      kinetic agent, which could be medicated conveniently in treating digestive
      motility disturbed diseases.

PMID- 14976884
TI  - [Clinical observation on treatment of gastro-esophageal reflux with modified
      zhizhu pill].
AB  - OBJECTIVE: To observe the therapeutic effect of modified Zhizhu pill (ZZP) in
      treating gastro-esophageal reflux disease (GERD) and to explore its mechanism.
      METHODS: Sixty-three GERD patients were randomly divided into the treated group
      (n = 30) and the control group (n = 33). The treated group was treated with ZZP
      100 ml, twice daily by orally taking half an hour before meal. The control group
      was treated with Ranitidine 0.15 g, twice daily and Cisapride 10 mg, three times
      a day by orally taking before meal. The therapeutic course for both groups was 8
      weeks. The changes of symptom scoring, endoscopic examination, esophageal
      pressure, 24 hrs monitoring on pH and blood level of motilin in the two groups
      were recorded and compared. RESULTS: After treatment, the symptom scoring,
      esophageal pressure, 24 hrs monitoring on pH and blood motilin level were
      improved in both groups (P < 0.05), and the improvement in the treated group was
      more significant than that in the control group (P < 0.05). CONCLUSION: ZZP has
      good effect in treating GERD.

PMID- 14976885
TI  - [Clinical study on treatment of severe acute respiratory syndrome with
      integrative Chinese and Western medicine approach].
AB  - OBJECTIVE: To summarize the clinical characteristics of severe acute respiratory
      syndrome (SARS) and observe the therapeutic effect with integrative Chinese and
      western medicine (ICWM) approach in treating patients with SARS. METHODS: Forty
      eight patients selected from the authors' hospital, whose diagnosis confirmed as
      SARS were analysed to sum-up the diagnostic type and basic feature of patients
      and the chief clinical characteristics. All the patients were randomly divided
      into the trial group and the control group, 24 in each. The control group was
      treated with the western medical therapeutic program and the trial group was
      treated with ICWM therapeutic program. The differences between the two groups
      were compared in terms of development of illness, time of using corticosteroid
      and absorption time of pulmonary inflammatory lesion, etc. RESULTS: Most patients
      were youth and adult aged between 18 to 40 years old, the initial symptom was
      mainly the high fever, accompanied with general soreness, chest stuffiness and
      cough, etc. The hospitalization time, body temperature fluctuation sustaining
      time and time of using corticosteroid in the trial group were shorter than those
      in the control group, showing significant difference (P < 0.05). ICWM treatment
      showed a better effect in defervescence and inflammatory lesion absorption time,
      but with no statistical significance. CONCLUSION: Patients of SARS are mainly
      youth and adults in the prime of life, fever always appears as the initiation of
      illness and some accompanying symptoms would appear. As compared with the western
      treatment, ICWM treatment could evidently shorten the course of illness, prevent
      the rebounding of fever and reduce the time of using corticosteroid.

PMID- 14976886
TI  - [Study on protective effect of shenfu injection on cardiac function of patients
      undergoing valve replacement].
AB  - OBJECTIVE: To investigate the protective effect of Shenfu injection (SFI) on
      cardiac function of patients undergoing valve replacement operation under cardio
      pulmonary bypass. METHODS: One hundred and twenty patients undergoing valve
      replacement operation under cardio-pulmonary bypass were randomly divided into
      the SFI group and the control group, 60 in each group. Intravenous infusion of 1
      ml/kg SFI was given to the SFI group, 30 min before anesthesia, and to the
      control group, equal volume of normal saline was given instead. The following
      indices were observed: (1) the hemodynamic changes occurred in the operational
      period; (2) the dosage of vaso-active drugs used during and after operation; (3)
      the post-operational recovery time of patients. RESULTS: The mean arterial
      pressure and heart rate in the SFI group during operation were higher, while the
      central venous pressure was lower than those in the control group (P < 0.05). The
      dosage of vaso-active drugs, such as dopamine, dobutamine, sodium nitroprusside
      and lidocaine, used during and after operation was lower, and the extubation time
      and the intensive care unit (ICU) staying time were shorter in the SFI group when
      compared with those in the control group (P < 0.05). CONCLUSION: SFI has certain
      protective effects on the cardiac function of patients undergoing valve
      replacement operation under cardio-pulmonary bypass.

PMID- 14976887
TI  - [Study on relationship between cellular immunity and TCM typing in patients with
      minimal residual leukemia].
AB  - OBJECTIVE: To analyse the correlation between the cellular immunity and TCM
      Syndrome typing of patients with minimal residual leukemia (MRI). METHODS: The
      analysis was performed by detecting cellular immunological parameters in 30 MRI
      patients, 55 healthy persons and 36 patients with acute leukemia (AL) using three
      fluoresceine-conjugated monoclonal antibodies and flow cytometer. RESULTS: As
      compared with those in the healthy persons, universal reductions of various
      parameters were shown in the MRI patients, including WBC count, absolute value of
      total T-lymphocytes, T-helper lymphocyte (P < 0.05) and total lymphocytes; the
      percentage and absolute value of NK cells (P < 0.01); and the percentages of
      total T-lymphocytes, CD4+ CD29+, T-suppressor cells and T-memory cells (P < 0.05
      or P < 0.01), but without any rising of absolute value. As compared with those in
      the patients with AL, parameters were similar in the two groups with
      insignificant difference. The disturbances, including the lowering on ratio of T
      helper/T-suppressor lymphocytes, in MRI patients of Qi-blood insufficiency type
      was the severest, that in the patients of Qi-Yin deficiency type was the mildest,
      and that in patients of Yin-deficiency with excess Fire type located between
      them. CONCLUSION: The immune function of MRI patients is low, belonging to the
      TCM Syndrome of vital energy deficiency with evil-lingering. Since the degree of
      cellular immune disturbance is different in various TCM Syndrome types,
      therefore, they should be treated with different dosages of different drugs.

PMID- 14976888
TI  - [Clinical observation on treatment of Stein-Leventhal syndrome caused sterility
      by combined use of clomiphene and Chinese nourishing shen and activating blood
      circulation drugs].
AB  - OBJECTIVE: To observe the efficacy of combination therapy of clomiphene and
      Chinese drugs for nourishing Shen and activating blood circulation (NSABC) in
      treating Stein-Leventhal syndrome caused sterility. METHODS: Sixty-two patients
      with anovulation caused sterility were randomly divided into the treated group (n
      = 32) and the control group (n = 30). The treated grop was treated with the
      combination therapy and the control group treated by the same dosage of
      clomiphene alone. RESULTS: After treatment, when comparing with that before
      treatment, the endocrine hormones in the treated group improved significantly,
      showing a markedly decrease of androgen and luteotropic hormone, and increase of
      estrogen (P < 0.001). The periodic ovulation rate in the treated group reached
      87%, the total pregnancy rate being 65.6%, with no occurrence of ovarian
      hyperstimulation syndrome (OHSS) and luteinized unruptured follicle syndrome
      (LUFS), while in the control group, the periodic ovulation rate was 66%, the
      total pregnancy rate 36.6%, with LUFS occurred in 4 patients. Comparison of the
      therapeutic effects between the two groups showed significant difference (P <
      0.05). CONCLUSION: The combination therapy of clomiphene and NSABC has a better
      therapeutic effect in treating Stein-Leventhal syndrome caused sterility than
      that of using clomiphene alone.

PMID- 14976889
TI  - [Study on glucose metabolic rate in non-small cell lung cancer patients with
      blood stasis syndrome and non-blood stasis syndrome].
AB  - OBJECTIVE: To study the difference of glucose metabolic rate in non-small cell
      lung cancer (NSCLC) patients with blood stasis syndrome and with non-blood stasis
      syndrome. METHODS: Whole body positron emission tomography (PET) and functional
      agent 2-[fluorine-18] fluorine-2-deoxy-glucose (18FDG) were used to detect the
      18FDG uptake value in regions of interest (ROI) in tumor tissue of patients.
      RESULTS: In patients with same pathologic type, the maximum and mean standardized
      uptake value (Max SUV and Mean SUV) were significantly higher in the blood stasis
      group than those in the non-blood stasis group (P < 0.01); it also showed the
      same in patients with NSCLC of phase I, II and III (P < 0.05), but the 18FDG
      uptake rate was obviously enhanced in patients of phase IV (P < 0.01).
      CONCLUSION: The glucose uptake in NSCLC patients of blood stasis syndrome was
      higher than that in those with of non-blood stasis syndrome.

PMID- 14976890
TI  - [Effect of anti-fibrosis compound contained serum on procollagen Type I and IV,
      matrix metalloproteinase and its tissue inhibitor-1 gene expression in HSC-LI90
      cell line].
AB  - OBJECTIVE: To study the effects of Anti-fibrosis Compound contained serum (AFCS)
      on procollagen type I and IV (ProC-I and ProC-IV), matrix metalloproteinase (MMP)
      and its tissue inhibitor (TIMP-1) gene expression in hepatic stellate cell line
      LI90 (HSC-LI90). METHODS: AFCS was prepared by gastric infusing different dosage
      (0.5 g/kg, 2.0 g/kg and 4.0 g/kg) of Anti-fibrosis Compound Recipe to rats. After
      HSC-LI90 cells were exposed to AFCS for 48 hrs, levels of ProC-I, ProC-IV, gene
      expression of MMP-2, MMP membrane type 1 (MT1-MMP) and TIMP-1 in the cells were
      detected by Northern blot, and gelatinase activity of MMP-2 was measured by
      zymography. RESULTS: AFCS of different concentrations could inhibit ProC-I and
      ProC-IV and TIMP-1 gene expression (P < 0.05 or P < 0.01), increase MT1-MMP gene
      expression (P < 0.01), but it showed no effect on gene expression and activity of
      MMP-2 (P > 0.05). CONCLUSION: Anti-fibrosis Compound Recipe has anti-liver
      fibrosis action, its effects in inhibiting TIMP-1 gene expression of HSC-LI90
      cells and promoting degradation of collagen might be one of the mechanisms of the
      action.

PMID- 14976891
TI  - [Experimental study on effect of gastrodia in inducing the differentiation of
      mesenchymal stem cells into neuron-like cells].
AB  - OBJECTIVE: To investigate the effect of gastrodia in extracorporeal oriented
      inducing the differentiation of mesenchymal stem cells into neuron-like cells.
      METHODS: Mesenchymal stem cells were separated from bone marrow of rats by wall
      sticking method, amplifying cultured in vitro, and differentiated into neuron
      like cells by oriented induction with gastrodia. The morphology of cells was
      observed under light microscopy, neuro-specific enolase (NSE), nestin and glial
      fibrillary acidic protein (GFAP) were detected by immunocytochemistry. RESULTS:
      Rats mesenchymal stem cells could be separated and amplified in vitro. After
      being induced by gastrodia for 2 hrs, most of the cells would be differentiated
      into meuron-like cells, revealing cytodendrite. By immunochemical staining, cells
      showed positive of NSE, nestin, and negative of GFAP. CONCLUSION: Rats'
      mesenchymal stem cells could be induced to differentiate into neuron-like cells.

PMID- 14976892
TI  - [Experimental study on anti-tumor effects of cortex Acanthopanacis senticosus in
      vivo and in vitro].
AB  - OBJECTIVE: To provide a basis for development and preparation of the new anti
      tumor agents from Cortex A-canthopanacis senticosus (CAS), through isolating the
      active substances from CAS and studying the anti-tumor effect of CAS extracts in
      vivo and in vitro. METHODS: The effects of CAS extracts and its isolated
      ingredients on tumor cell proliferation in vitro was determined by 3H-TdR
      incorporation; the anti-tumor component of CAS was isolated and purified by
      chromatography; the tumor bearing mice model was established by injecting tumor
      cell subcutaneously, and the model was used to observe the anti-tumor effect of
      CAS extract administered through gastrogavage. RESULTS: CAS extract showed
      obvious inhibition on tumor cell proliferation originated from multiple tissues
      (P < 0.01) and displayed a better dose-effect relationship. After orally taken
      CAS extract, the general condition of mice in the experimental group were better
      than that in the untreated control group, revealing a slower growth and
      significantly prolonged survival period (P < 0.01). A protein component, having
      inhibitory effect on tumor cell proliferation and the molecular weight was 64
      kda, it was isolated by the thin layer gel chromatography. CONCLUSION: CAS has
      not only the in vitro inhibitory effect on cell proliferation of multiple kinds
      of tumor, but also a good anti-tumor effect in vivo. The anti-tumor activity of
      CAS is correlated with a protein component with the molecular weight of 64 kda.
      Further isolation, purification, study on mechanism will provide scientific
      evidence for clinical application and development of CAS in anti-tumor effect.

PMID- 14976893
TI  - [Molecular mechanism of epimedium flavonoids in immune homeostasis remodeling in
      aged rats revealed by lymphocyte gene expression profile].
AB  - OBJECTIVE: To elucidate the gene regulatory pattern of Epimedium flavonoids (EF)
      in immune homeostasis remodeling in the aged rats. METHODS: (1) To quantitatively
      analyse the apoptosis percentage of lymphocyte in spleen of aged, young and EF
      treated rats using flow cytometry. (2) To analyse the lymphocyte gene expression
      profiles of different groups using gene chips (Rat Genome U34A). RESULTS: (1)
      Detection of lymphocyte apoptosis percentage showed that there was significant
      difference in comparing between aged group and young group, between EF treated
      group and aged group (P < 0.01). (2) As compared with that in the young group, in
      the aged group, 116 genes were up-regulated and 215 down-regulated. As compared
      with that in the old group, in the EF treated group, 447 genes were up-regulated
      and 456 down-regulated, which involved the aspects as cell apoptosis and cell
      proliferation regulation, etc. CONCLUSION: (1) The expression pattern
      characterized by up-regulation of apoptosis promoting genes expression and down
      regulation of apoptosis inhibiting genes expression, is the important gene
      background of immuno-homeostasis imbalance in the aged. (2) The role of EF is to
      reverse the abnormal changes of gene expressions with opposite functions, i.e.
      the apoptosis promoting and inhibiting, proliferation enhancing and antagonizing
      genes, to reconstruct a beneficial equilibrium of gene expression and thus to
      further remodel the immuno-homeostasis in the aged.

PMID- 14976894
TI  - [Effect of panax notoginseng saponin on procoagulant activity and differentiation
      induction in NB4 cells].
AB  - OBJECTIVE: To investigate the effect of Panax notoginseng saponin (PNS) on
      procoagulant activity (PCA) and differentiation induction in NB4 cells. METHODS:
      After NB4 cells were treated with PNS, the recalcification time, PCA and TF-mRNA
      expression in NB4 cells were tested by RT-PCR. The inhibitory effect of PNS on
      NB4 cell proliferation was analysed by MTT method, NBT assay, cell morphological
      observation and flow cytometry. RESULTS: (1) PNS of all concentrations could
      significantly prolong the recalcification time and lower the PCA level in NB4
      cells in time-concentration-dependent manner. Simultaneously it down-regulated
      the expression of TF-mRNA. (2) PNS could partially inhibit the NB4 cell
      proliferation. (3) PNS could raise the NBT reducing capability of NB4 cells (P <
      0.05). And morphological examination showed the differentiating tendency of
      monocyte and macrophage. CONCLUSION: PNS could reduce the procoagulant activity
      and TF-mRNA expression in NB4 cells, and partially induce the differentiation of
      NB4 cells, therefore, it is hopeful to be a new anti-coagulant agent.

PMID- 14976895
TI  - [Clinical observation on effect of combined therapy of pamidronati sodium and
      shenfu injection in treating multiple myeloma caused ostealgia].

PMID- 14976896
TI  - [Observation on effect of activated vision-enhancing granule in treating vitreous
      hemorrhage].

PMID- 14976897
TI  - [Clinical observation on prevention and treatment of 39 patients with premonitory
      stroke by xidi granule].

PMID- 14976898
TI  - [Preliminary analysis on the method of efficacy evaluation used in clinical
      articles issued in Chinese journal of integrated traditional and Western
      medicine].

PMID- 14976899
TI  - [Cluster analysis of variables in liver syndrome of TCM].

PMID- 14976900
TI  - [TCM treatment of asthma and histocompatible complexus].

PMID- 14976901
TI  - [Molecular mechanism and TCM treatment and prevention of endotoxin caused shock].

PMID- 14976902
TI  - [Minute of the 12th National Conference on Integrative Chinese and Western
      Medicine in Liver Diseases].

PMID- 14976903
TI  - Good measurement for good improvement work.
AB  - PURPOSE: To provide guidance on using measurement to support the conduct of local
      quality improvement projects that will strengthen the evaluation of results and
      increase their potential for publication. TARGET GROUP: Individuals leading
      quality improvement efforts who wish to enhance their use of measurement.
      PROCEDURES TO PROMOTE GOOD MEASUREMENT: Eleven procedures are offered to promote
      intelligent measurement in quality improvement research that may become
      publishable: 1. Start with an important topic 2. Develop a clear aim statement 3.
      Turn the aim statement into key questions 4. Develop a theory about causes and
      effects, process changes and predictable sources of variation 5. Construct a
      research design and accompanying dummy data displays to answer your primary
      research questions 6. Develop and use operational definitions for each variable
      needed to make your dummy data displays 7. Design a data collection plan to
      gather information on each variable that will enable you to generate reliable,
      valid, and sensitive measures related to each research question 8. Pilot test the
      data collection plan, construct preliminary data displays, and revise your
      methods based on what you learn 9. Stay close to the data collection process as
      the data plan goes from idea to execution 10. Perform data analysis and display
      results in a way that answers your key questions. 11. Review and document the
      strengths and limitations of your measurement work and use this knowledge to
      guide intelligent interpretation of the observed results.

PMID- 14976904
TI  - Study designs for PDSA quality improvement research.
AB  - OBJECTIVE: The purpose of this article is to discuss strengths and weaknesses of
      quasi-experimental designs used in health care quality improvement research. The
      target groups for this article are investigators in plan-do-study-act (PDSA)
      quality improvement initiatives who wish to improve the rigor of their
      methodology and publish their work and reviewers who evaluate the quality of
      research proposals or published work. SUMMARY: A primary purpose of PDSA quality
      improvement research is to establish a functional relationship between process
      changes in systems of health care and variation in outcomes. The time series
      design is the fundamental paradigm for demonstrating such functional
      relationships. The rigor of a PDSA quality improvement study design is
      strengthened using replication schemes and research methodology to address
      extraneous factors that weaken validity of observational studies. CONCLUSION: The
      design of PDSA quality improvement research should follow from the purpose and
      context of the project. Improving the rigor of the quality improvement literature
      will build a stronger foundation and more convincing justification for the study
      and practice of quality improvement in health care.

PMID- 14976905
TI  - Guidelines for appraisal and publication of PDSA quality improvement.
AB  - Plan-do-study-act (PDSA) quality improvement is the application of the scientific
      method to implement and test the effects of change ideas on the performance of
      the health care system. Users of quality improvement could benefit with markers
      to gauge the "best" science. Four core questions can determine the value of a
      quality improvement study: Is the quality improvement study pertinent and
      relevant? Are the results valid? Are appropriate criteria used to interpret the
      results? Will the study help you with your practice or organization of care? A
      set of guidelines is provided to help answer these questions. Similar guidelines
      exist for randomized clinical trials and clinical-epidemiologic observational
      studies. Analogous to these existing research guidelines, the PDSA quality
      improvement guidelines will provide researchers and reviewers with succinct
      standards of methodological rigor to assist in critical appraisal of quality
      improvement protocols and publications.

PMID- 14976906
TI  - Measurement of nursing practice models using multiattribute utility theory:
      relationship to patient and organizational outcomes.
AB  - Workforce shortages are challenging administrators in the health care
      environments to examine existing models of providing care. Although
      characteristics of nursing care delivery contribute in important ways to the
      success or failure of hospital care, factors common to all practice models have
      not been identified nor have measurement strategies been designed that assess the
      impact of care on patient and organizational outcomes. The purpose of this study
      was to test a measurement model of nursing practice that was developed using
      multiattribute utility theory. A total of 24 factors identified by expert nurse
      administrators as being common to all nursing practice models were mathematically
      formulated into a multidimensional composite index that represented the degree to
      which a practice model on a nursing unit approached the professional ideal. The
      index was tested with 298 registered nurses working on 28 medical surgical
      nursing units in 3 hospitals. The model was evaluated in 2 ways: first by
      comparing the composite index scores to a qualitative appraisal of the nursing
      unit's practice model and patient and organizational outcomes. Secondly,
      individual factors in the model were evaluated in the same manner. While the
      composite index was not fully validated, there is strength in the evidence of the
      relationship between individual factors and outcomes. Specifically, factors that
      addressed interactions among health care team members were most often related to
      outcomes.

PMID- 14976907
TI  - OSF healthcare's journey in patient safety.
AB  - This article describes OSF Healthcare's recent journey in patient safety. It
      discusses the involvement of its 6 hospitals in collaboration with each other and
      the Institute for Healthcare Improvement. OSF focused on a strategy for
      decreasing adverse drug events (ADEs). They worked on impacting 4 major areas:
      safety culture, high-risk medication, dispensing of medication, and medication
      reconciliation. By doing this, OSF decreased its rate of ADEs per 1000 units of
      medication administered from 3.84 to 1.39 over the course of 20 months.

PMID- 14976908
TI  - Learning helpers: how they facilitated improvement and improved facilitation-
      lessons from a hospital-wide quality improvement initiative.
AB  - Quality improvement is a leading approach to the difficult yet inevitable task of
      managing organizational change. The literature suggests that facilitators can
      help organizations apply improvement principles and tools but it is unclear how
      facilitators actually do this and how they develop their own skills. Using a case
      study design we therefore examined how facilitators worked with 93 improvement
      projects in over 1000 sessions at one Swedish university hospital where
      systematic process improvement was successfully established over a 5-year period.
      They facilitated improvement by providing a framework and methods' support for
      improvement efforts--relying on experiential learning rather than didactic
      teaching--while letting clinical teams and managers maintain control over the
      content of improvement projects. They developed extensive experience that they
      documented and could transfer between teams, so that each team could benefit from
      lessons learned elsewhere. They improved facilitation through participant
      feedback and systematic review and reflection regarding their own practice. We
      suggest that facilitators can help organizations manage change by assuming
      responsibility for demanding tasks related to improvement work, developing
      specialized skill and extensive experience regarding improvement, and
      transferring insights across the organization, while using a learning approach
      throughout including to their own work.

PMID- 14976909
TI  - Patient satisfaction as a predictor of return-to-provider behavior: analysis and
      assessment of financial implications.
AB  - Although customer loyalty is frequently cited as a benefit of patient
      satisfaction, an empirical link between the two has not, to our knowledge, ever
      been statistically established in a hospital setting. The goal of the present
      study was to evaluate the relationship between self-reported patient satisfaction
      measures and subsequent return to the provider for care at a large academic
      medical center. Data from all adult medical patients responding to a patient
      satisfaction survey distributed by a large midwestern academic medical center
      during fiscal year 1997 (n = 1485) were analyzed. Response patterns were examined
      as they related to whether patients returned to the provider during the
      subsequent 2-year period. Analyses suggested that return-to-provider was
      associated with only a minority of the satisfaction items (approx. 11%). All
      items showing a significant relationship measured perceptions of how well
      physicians and nurses attended to, and provided information to, patients and
      their families. Although the size of these relationships was generally small, the
      estimated financial implications are substantial. Other implications of these
      findings for planning effective service improvement initiatives as well as
      improving patient survey design are discussed.

PMID- 14976910
TI  - Are doctors unhappy? A study of residents with an open interview form.
AB  - Several recent reports show that many physicians feel discontented and unhappy
      with their work situation. This could in part be due to a decline in status, loss
      of influence on health care organization, reduced wages etc. It is important to
      find ways to better understand their experiences of working life to get more
      facets of this issue. The Medical Management Centre at the Karolinska Institute
      in Stockholm offers courses in leadership for physicians in specialty training
      (residency). Participants in 2 courses were used in a study of their views of
      their work situation and their employer, using an open interview form. The
      results with the residents in the present study do not support the statement that
      physicians are unhappy. On the contrary, findings in the study indicate that they
      have a predominantly positive view of their work situation and of their employer.
      It is proposed that the mixed feelings they show to some extent is a natural
      stage in professional development. A possible way for achieving a better dialogue
      between physicians and managers is suggested.

PMID- 14976911
TI  - QMHC interview. Continuing the journey to patient safety. Interview by Mary C.
      Odwazny.

PMID- 14976912
TI  - [A novel paradigm and new targets in cancer therapy].

PMID- 14976913
TI  - [Clinical and morphologic characteristics of gastrointestinal stromal tumors].

PMID- 14976914
TI  - [Specifics of radiotherapy in hormone-dependent breast cancer].

PMID- 14976915
TI  - [Comparative characteristics of hormonal status in patients with receptor
      negative cancers of the breast and of the endometrium].
AB  - 2,429 breast cancer patients and 478 patients with endometrial carcinoma were
      examined. It was suggested that the absence of estrogen receptors (ER) and/or
      progesterone receptors (PR) should be accounted for by peculiar endocrine
      features (including those of reproductive function) of the patients' medical
      history and/or hormonal metabolic status (body weight, estrogenemia, insulinemia,
      etc.) at clinical detection of tumor. The differences between breast and
      endometrial cancer in receptor-negative (R-) incidence were related to age
      (decade of lifespan) and menstrual cycle. Indices describing hormone-metabolic
      status were used for identification of receptor-negative or receptor-positive
      status of tumor (reliability of 65-70% for breast cancer and 75-80%--endometrial
      carcinoma) when it was not feasible under laboratory conditions.

PMID- 14976916
TI  - [Vascular endothelial growth factor and plasminogen activators in endometrial
      carcinoma and hyperplasia].
AB  - Vascular endothelial growth factor (VEGF) and such plasminogen activation system
      components as uPA, PAI-1 and tPA were determined by enzyme immunoassay methods in
      endometrial tumors from 121 patients and 18 samples of endometrial hyperplasia of
      varying degree. Endometrial carcinoma concentrations of uPA vs. PAI-1 were
      significantly higher than those in hyperplasia. Significant direct correlations-
      uPA vs. VEGF, uPA vs. PAI-1 and PAI-1 vs. VEGF--were established in endometrial
      tumors, and inverse ones for tPA vs. uPA and tPA vs. VEGF. A marked correlation
      with prognostic factors was found for PAI-1 and VEGF: levels of these proteins
      were relatively higher in cases of tumor progression (FIGO stage and deeper
      myometrial invasion), poor cell differentiation, and loss of hormone sensitivity.
      Higher uPA expression was associated with deeper myometrial invasion while, in
      endometrial tumors with unfavorable prognosis, it was VEGF level alone that was
      significantly higher.

PMID- 14976917
TI  - [Quantitative growth characteristics of pulmonary metastases in cutaneous
      melanoma].
AB  - The dynamics of growth of skin melanoma metastases to the lung versus
      chemoimmunotherapy regime has been assessed quantitatively. Natural course of
      such pathology at advanced stages was found to correspond to the exponent. An
      analytical procedure for plotting graphs was suggested, which will allow to
      estimate the kinetic characteristics of tumor growth. This in turn can be used as
      an indicator of therapy efficacy.

PMID- 14976918
TI  - [Clinical significance of macroscopic 5-aminolevulinic acid (ALA)-inducer
      fluorescence in transurethral resection of non-invasive bladder cancer].
AB  - Macroscopic fluorescence which is induced with aminolevulinic acid (ALA) allows
      visualizing of small flat tumors, carcinoma in situ, true neoplasm margins and
      dysplasias of the bladder. Following ALA instillation, cystoscopy was performed
      under both standard and blue light illumination. In a prospective randomized
      multicenter study, 102 patients underwent TUR of bladder tumor(s) either with
      white light or ALA-fluorescence. Significant reduction in the number of residual
      tumours was detected in 59% (p = 0.005) after 8 weeks, 3 months--in 58% (p =
      0.002) and 6 months in 38% (p = 0.01) respectively.

PMID- 14976919
TI  - [Precancerous conditions of the prostate--histologic and morphometric
      investigation].
AB  - The nuclear ploidy of epithelial cells in biopsy specimens from precancerous
      prostatic tissues was investigated in 80 patients. Histological specimens stained
      after Felgen were examined using an Imager-CG computer analyzer (Avtan-Sun
      protocol). The study compared interphase nuclei of intact prostate epithelial
      cells, low-grade prostatic intraepithelial neoplasia, high-grade prostatic
      intraepithelial hyperplasia (PIH) and atypical small acinar proliferation.
      Nuclear ploidy was shown to vary with said conditions: high-grade (PIH) should be
      considered an obligatory precursor of cancer while the other two conditions-
      potential precursors. These correlations may be used to improve the accuracy of
      morphological examination of biopsy specimens.

PMID- 14976920
TI  - [Intravascular large b-cell lymphoma: case report].
AB  - Intravascular lymphoma has an aggressive course. Its clinical manifestations may
      vary and most often include fever, skin lesions and mental disorders. Diagnosis
      can be made by biopsy of an affected organ. In 30-50% of cases, intravascular
      lymphoma is diagnosed post mortem. Poor diagnosis is mostly due to a variety of
      clinical manifestations and an aggressive course. Yet, in cases of timely
      diagnosis, complete remission can be achieved by combination chemotherapy in
      approximately 55%. We report a clinical cases of intravascular B-cell lymphoma
      which was verified in a post mortem immunochemical investigation.

PMID- 14976921
TI  - [Experience with turbulent magnetic field as a component of breast cancer
      therapy].
AB  - No adverse side-effects were reported in an investigation of the antitumor effect
      of turbulent magnetic field (TMF) carried out as a component of preoperative
      chemoradiotherapy for breast cancer at the Center's Clinic. The study group
      included 114 patients with locally advanced tumors(T3, N1-N3, M0). According to
      the clinical, roentgenological and histological evidence on the end-results, the
      procedure was highly effective. Also, it was followed by shorter and less
      extensive postoperative lymphorrhea.

PMID- 14976922
TI  - [Assessment of the intermediate and the late results of surgery for gastric stump
      cancer].
AB  - The data on the results of therapy for gastric stump cancer in 176 patients were
      evaluated. Reoperation was carried out in 81 (46.0%); postoperative lethality was
      7.4%. Combined abdominothoracic or thoracic alone access was available in all
      cases. It is suggested that relatively high radicality is assured when combined
      surgery for gastric stump recurrence is used. Overall 5-year survival was
      reported in patients radically operated on for relapse.

PMID- 14976923
TI  - [Ultrasound diagnosis of acute cancer-related colorectal obstruction].
AB  - Partial or complete obstruction was diagnosed by means of sonography with water
      filling (hydrosonography) in 48 patients with rectal or colonic cancer. The
      procedure appeared highly effective in detecting pathological lesions larger than
      1.0 cm. It may be useful under urgent surgical conditions as a method of choice
      in diagnosing the nature of lesion, size, endophytic growth or grade of invasion.
      Hydrosonography using retrograde contrast filling may considerably enhance the
      potential of standard and transabdominal scanning.

PMID- 14976924
TI  - [Possibilities of using low-intensity radio-frequency magnetic field as a
      component in cancer therapy].

PMID- 14976925
TI  - [Drainage-free management of patients after radical surgery for breast cancer].
AB  - The paper deals with drainage-free management of disease and therapy after
      radical surgery for breast cancer. The data on the immediate results of surgery
      were assessed in 168 patients. Suture of a skin flap to the thoracic wall closed
      a gap in axillary area while ultrasound monitoring of the wound and aspiration of
      fluid made keeping track of postoperative recovery possible. Wound complications
      were registered in 51 patients (30.4%) serotoma--35 (20.8%).

PMID- 14976926
TI  - [Novel method of lymphatic dissection in rectal cancer with metastases to the
      inguinal lymph nodes].

PMID- 14976927
TI  - [Reconstruction of the oral cavity floor, mandibular segment and cheek dislocated
      by myocutaneous flap sutured to the thorax during surgery for locally advance
      tumor].

PMID- 14976928
TI  - [Mediastinal echinococcus].

PMID- 14976929
TI  - [Current issues in adjuvant hormone therapy of breast cancer].

PMID- 14976931
TI  - Healthy eating. In a nutshell. Big nutrition in a small package.

PMID- 14976930
TI  - [Use of interleukin-2 (proleukin, aldesleukin) in oncological practice].

PMID- 14976932
TI  - Good fats. Essential fatty acids for your health.

PMID- 14976933
TI  - Sports injuries. Nursing yourself back to health.

PMID- 14976934
TI  - The Blind Boys of Alabama--singing from the soul.

PMID- 14976935
TI  - Weight-loss scams. What to watch out for.

PMID- 14976936
TI  - All about laser eye surgery.

PMID- 14976937
TI  - OTC survival guide. 20 questions. Do you how to safely get the greatest benefit
      from over-the-counter (OTC) drugs and products? Answer these 20 questions and
      find out!

PMID- 14976938
TI  - OTC survival guide. Complications. Care. Over-the-counter help for what ails you.

PMID- 14976939
TI  - OTC survival guide. FAQs on OTCs. Here are answers to your questions about over
      the-counter remedies.

PMID- 14976940
TI  - Research profile. The apple shape. Causes and effects.

PMID- 14976941
TI  - Vitamin C. Give a boost to your immune system.

PMID- 14976942
TI  - Resource guide 2004. New products. High technology, ease of use, and convenience
      characterize today's new diabetes products.

PMID- 14976943
TI  - Resource guide 2004. Class action.  There are now five classes of diabetes pills
      and several combination oral meds as well. Each has a different way of helping
      you control your diabetes.

PMID- 14976944
TI  - Resource guide 2004. Insulin. There are many different insulins for many
      different situations and lifestyles. This section should help you and your doctor
      decide which insulin or insulins are best for you.

PMID- 14976945
TI  - Resource guide 2004. Insulin delivery.
AB  - Syringes...pumps...jet infectors...pens...infusers...they all do the same basic
      thing--deliver insulin. These items carry insulin through the outermost layer of
      skin and into fatty tissue so it can be used by the body. This section will also
      cover injection aids, products designed to make infecting easier.

PMID- 14976946
TI  - Resource guide 2004. Blood glucose. Monitors and data management systems.
AB  - Before you buy a blood glucose monitor (also known as a blood glucose meter),
      check with your doctor and diabetes educator. Make sure the one you choose is
      well suited to your particular needs. You might want to have one at home and one
      for use at school or the office.

PMID- 14976947
TI  - Resource guide 2004. Products for treating low blood glucose.

PMID- 14976948
TI  - Resource guide 2004. Wound gels and prescription lotions.

PMID- 14976949
TI  - Resource guide 2004. Urine testing.

PMID- 14976950
TI  - Resource guide 2004. Carrying cases.

PMID- 14976951
TI  - Resource guide 2004. Medical identification products.
AB  - Health care and emergency personnel encourage people with diabetes to wear some
      form of medical identification. The reason is obvious: such identification can
      save time in an emergency and may save your life.

PMID- 14976952
TI  - Resource guide 2004. Manufacturers and exclusive distributors.

PMID- 14976953
TI  - Research profile. Gestational diabetes. Are prediction and prevention possible?

PMID- 14976954
TI  - Why we're losing the war against obesity.
AB  - About two-thirds of all adult Americans are fat, but what's alarming is that more
      children and teenagers are overweight, and as they grow up, their health problems
      will have huge repercussions for our society.

PMID- 14976955
TI  - Diet Inc.
AB  - As more Americans buy in to Dr. Atkins' commandments to cut out carbohydrates and
      feast on fats, purveyors of mass packaged food jockey for market primacy with low
      carb product intros.

PMID- 14976956
TI  - Trouble in store.
AB  - As boomers age, food retailers are faced with weighty questions on what customers
      want, and whether it's healthy or not.

PMID- 14976957
TI  - Mucogingival surgery.

PMID- 14976958
TI  - Unrecognized bilateral posterior shoulder dislocation diagnosed by ultrasound
      (2003:11b).

PMID- 14976959
TI  - A frontal mass (2004:2a).

PMID- 14976960
TI  - Serum-stable and long-circulating, PEGylated, pH-sensitive liposomes.
AB  - pH sensitive liposomes were prepared using a terminally-alkylated copolymer of N
      isopropylacrylamide (NIPAM) and methacrylic acid (MAA) and poly(ethylene glycol)
      phospholipid derivative. The pH-triggered content release was evaluated before
      and after incubation in serum. Pharmacokinetic and biodistribution profiles of
      the formulations were established in rats. This study showed that a pH-sensitive,
      serum-stable and long-circulating liposomal formulation can be produced.

PMID- 14976961
TI  - [The new measures of the repairing of massive deep burn wounds in a large burn
      area].

PMID- 14976962
TI  - [Lay stress on research of wound healing to upgrade burn management].

PMID- 14976965
TI  - New treatment hope for prostate cancer.

PMID- 14976969
TI  - Pieter Bruegel the Elder (1525/1530-1569).

PMID- 14976970
TI  - Gates grant boosts tuberculosis vaccine research. US82.9 million dollars grant
      will double global spending on new tuberculosis vaccines.

PMID- 14976971
TI  - Croatian campaign promotes lifestyle change. Programme to be model for prevention
      campaigns in eastern Europe.

PMID- 14976972
TI  - Global Fund suspends payments to Ukraine.

PMID- 14976973
TI  - S African president criticised for lack of focus on AIDS.

PMID- 14976974
TI  - Spain makes plans to combat sex tourism.

PMID- 14976975
TI  - Rural health care support mechanism. Final rule; denial of petition for
      reconsideration.
AB  - In this document, the Commission modifies its rules to improve the effectiveness
      of the rural health care support mechanism, which provides discounts to rural
      health care providers to access modern telecommunications for medical and health
      maintenance purposes. Because participation in the rural health care support
      mechanism has not met the Commission's initial projections, the Commission amends
      its rules to improve the program, increase participation by rural health care
      providers, and ensure that the benefits of the program continue to be distributed
      in a fair and equitable manner. In addition, the Commission denies Mobile
      Satellite Ventures Subsidiary's petition for reconsideration of the 1997
      Universal Service Order.

PMID- 14976976
TI  - Canadian hospitals call for restrictions on single-use devices.

PMID- 14976977
TI  - Japanese leprosy patients continue to fight social stigma. 2 years after landmark
      court ruling, incarcerated patients are still fearful of returning home.

PMID- 14976978
TI  - Coronary calcification score: the coronary-risk impact factor.
AB  - CONTEXT: Identification of asymptomatic high-risk individuals is integral to
      current policies for preventing coronary heart disease, but existing methods of
      estimating risk lack sensitivity. To overcome this limitation increasing use is
      being made of non-invasive methods to detect subclinical coronary artery disease-
      eg, computed tomography (CT) to scan for coronary artery calcification. The
      location and extent of calcification correlate closely with pathological and
      angiographic abnormalities, but whether such calcification predicts clinical
      events, especially in younger individuals, is equivocal. Most data on coronary
      calcification have been obtained with electron-beam CT, but recently multislice
      CT, which is more versatile, less expensive, and available in most large
      hospitals, has been increasingly used. STARTING POINT: Leslee Shaw and colleagues
      (Radiology 2003; 228: 826-33) showed that the coronary calcification score
      predicted total mortality within subsets of patients classified at low,
      intermediate, or high risk according to Framingham criteria. In a cohort of over
      10000 individuals, 5-year risk-adjusted survival was 95% when the score was over
      1000 compared with 99% for scores of 10 or less. These results agree with other
      recent studies showing strong correlations between coronary calcification and
      coronary heart disease events. WHERE NEXT? The increasing use of multislice CT
      scanners should generate more data for comparison with those obtained from
      electron-beam CT. Radiation dose, which is higher with multislice than with
      electron-beam procedures, needs to be reduced, and calcification in scans needs
      to be quantified more accurately than with existing computer-based analyses.
      Further studies are needed to establish the predictive power of the coronary
      calcification score for clinical events and the effects of therapeutic
      intervention on both these outcomes. It would also be worth investigating the
      relation between coronary calcification and risk factors not quantified in
      Framingham-based estimates, including familial and racial predisposition to
      premature coronary heart disease.

PMID- 14976979
TI  - Is trafficking a health issue?

PMID- 14976980
TI  - Risks and responsibilities: guidelines for interviewing trafficked women.

PMID- 14976981
TI  - Medicare program; rural health clinics: amendments to participation requirements
      and payment provisions; and establishment of a quality assessment and performance
      improvement program. Final rule.
AB  - This final rule amends Medicare certification and payment requirements for rural
      health clinics (RHCs) as required by the Balanced Budget Act of 1997 (BBA). It
      changes the definition of a qualifying rural shortage area in which a Medicare
      RHC must be located; establishes criteria for identifying RHCs essential to
      delivery of primary care services that we can continue to approve as Medicare
      RHCs in areas no longer designated as medically underserved; and limits waivers
      of certain nonphysician practitioner staffing requirements. This final rule
      imposes payment limits on provider-based RHCs and prohibits "commingling" (the
      use of the space, professional staff, equipment, and other resources) of an RHC
      with another entity. The rule also requires RHCs to establish a quality
      assessment and performance improvement program that goes beyond current
      regulations. Finally, this final rule addresses public comments received on the
      February 28, 2002 proposed rule and makes other revisions for clarity and
      uniformity and to improve program administration.

PMID- 14976982
TI  - The 20-hydroxyecdysone-induced cellular arrest in G2 phase is preceded by an
      inhibition of cyclin expression.
AB  - We have studied the effect of 20-hydroxyecdysone (20E) on cellular proliferation
      in IAL-PID2 cell line established from imaginal wing discs of Plodia
      interpunctella. Flow cytometry analysis demonstrated that 20E induced an arrest
      of cells in G2 phase. To determine whether this arrest was due to an effect of
      20E on cyclin expression, we cloned two cDNA fragments, named PcycA and PcycB,
      encoding, respectively, Plodia cyclins A and B. Using PcycA and PcycB probes, we
      have demonstrated that 20E induced a sharp decrease in the levels of cyclin A and
      B expression. Studies of induction pattern of Plodia HR3 transcription factor by
      20E revealed that its induction preceded the decrease of cyclins transcripts. An
      exposure of cells to 20E in the presence of juvenile hormone (JH) led to a change
      in the kinetic of PHR3 induction and prevented both the decline of cyclin A and B
      expression and the G2 arrest. This effect of JH provides an additional argument
      for the existence of a correlation between cyclin transcripts level and G2
      arrest. For the first time in insects, these findings bring evidence that
      ecdysteroids regulate cellular proliferation by acting on cell cycle regulators
      as cyclins.

PMID- 14976983
TI  - Exploring the sialome of the blood-sucking bug Rhodnius prolixus.
AB  - Rhodnius prolixus is a Hemiptera that feeds exclusively on vertebrate blood in
      all life stages. Its salivary glands produce potent pharmacological substances
      that counteract host hemostasis, including anti-clotting, anti-platelet, and
      vasodilatory substances. To obtain a further insight into the salivary
      biochemical and pharmacological complexity of this insect, a cDNA library was
      randomly sequenced, and salivary gland homogenates were fractionated by HPLC to
      obtain aminoterminal sequences of abundantly expressed proteins. Results indicate
      a remarkable expansion of the lipocalin family in Rhodnius salivary glands, among
      other protein sequences described. A summary of 31 new full length proteins
      deducted from their mRNA sequence is described, including several new members of
      the nitrophorin, triabin, and pallidipin families. The electronic version of the
      complete tables is available at
      http://www.ncbi.nlm.nih.gov/projects/vectors/rhodnius_prolixus.

PMID- 14976984
TI  - HeLp, a heme-transporting lipoprotein with an antioxidant role.
AB  - Plasma lipoproteins involved in lipid transport are target for free radical
      evoked pathological conditions in several mammalian models. The main
      hemolymphatic protein of Boophilus microplus is a heme-binding lipoprotein (HeLp,
      for Heme LipoProtein) that carries dietary heme produced from degradation of
      vertebrate hemoglobin to tissues of the tick. Addition of heme to phospholipid
      liposomes resulted in intense lipid peroxidation, which was inhibited by addition
      of HeLp. HeLp prevented lysis of red blood cells by heme. HeLp also inhibited
      reactions of heme with tert-butyl hydroperoxide (t-BOOH) or hydrogen peroxide.
      HeLp, quite differently from other lipoproteins, presents a protective intrinsic
      mechanism to counteract heme toxicity, while preserving the heme molecule to be
      reused by the tick. This is the first report of a lipoprotein acting as an
      antioxidant particle against heme-induced radical damage.

PMID- 14976985
TI  - Beta-1,3-glucan recognition protein-2 (betaGRP-2)from Manduca sexta; an acute
      phase protein that binds beta-1,3-glucan and lipoteichoic acid to aggregate fungi
      and bacteria and stimulate prophenoloxidase activation.
AB  - We have isolated and characterized a new beta-1,3-glucan recognition protein that
      is present in Manduca sexta cuticle and hemolymph. This 52 kDa protein,
      designated betaGRP-2, is 57% identical in sequence to betaGRP-1 from larval
      hymolymph of the same insect. BetaGRP-2 differs from betaGRP-1 in its absence of
      the naive larvae before the wandering stage begins. Transcription of the betaGRP
      2 was up-regulated in larvae challenged with yeast or bacteria. BetaGRP-2
      contains a region with sequence similarity to several glucanases but lacks
      glucanase activity. It aggregates yeasts and bacteria to, perhaps, limit the
      spread of invading cells and ensure a localized defense reaction. BetaGRP-2 binds
      laminarin and lipoteichoic acid, but not lipopolysaccharide. Laminarin-triggered
      prophenoloxidase activation was greatly enhanced in the induced larval hemolymph
      supplemented with purified betaGRP-2. Complementing other studies on pattern
      recognition molecules in M. sexta, these results indicate that a complex system
      of protein sensors is an integral component of the insect immune system and that
      different recognition molecules have overlapping binding specificity and
      functions.

PMID- 14976986
TI  - Current awareness on yeast.

PMID- 14976987
TI  - Analysis of glycan structures on the 120 kDa aminopeptidase N of Manduca sexta
      and their interactions with Bacillus thuringiensis Cry1Ac toxin.
AB  - The Bacillus thuringiensis Cry1Ac toxin specifically binds to a 120 kDa
      aminopeptidase N (APN) receptor in Manduca sexta. The binding interaction is
      mediated by GalNAc, presumably covalently attached to the APN as part of an
      undefined glycan structure. Here we detail a simple, rapid and specific chemical
      deglycosylation technique, applicable to glycoproteins immobilized on Western
      blots. We used the technique to directly and unambiguously demonstrate that
      carbohydrates attached to 120 kDA APN are in fact binding epitopes for Cry1Ac
      toxin. This technique is generally applicable to all putative Cry toxin/receptor
      combinations. We analyzed the various glycans on the 120 kDA APN using
      carbohydrate compositional analysis and lectin binding. The data indicate that in
      the average APN molecule, 2 of 4 possible N-glycosylation sites are occupied with
      fucosylated paucimannose [Man(2-3)(Fuc(1-2)GlcNAc(2)-peptide] type N-glycans.
      Additionally, we identified 13 probable O-glycosylation sites, 10 of which are
      located in the Thr/Pro rich C-terminal "stalk" region of the protein. It is
      likely that 5-6 of the 13 sites are occupied, probably with simple [GalNAc
      peptide] type O-glycans. This O-glycosylated C-terminal stalk, being GalNAc-rich,
      is the most likely binding site for Cry1Ac.

PMID- 14976988
TI  - Sham surgery: not an oxymoron.

PMID- 14976989
TI  - Heart failure topics from NASPE 2003.

PMID- 14976990
TI  - The European Society of Cardiology working group on heart failure: Heart Failure
      Update 2003.

PMID- 14976991
TI  - Patient cost-sharing innovations: promises and pitfalls.
AB  - Over the next decade, health plans and employers will refine patient cost sharing
      to encourage workers to seek more cost-effective care, according to a panel of
      market and health policy experts at a Center for Studying Health System Change
      (HSC) conference. Instead of using a single, large deductible, employers and
      health plans will likely vary patient cost sharing by choice of provider, site
      and type of service, so patients choosing less effective care options pay more.
      Employers also will try to limit financial hardships for low-income workers by,
      for example, varying cost sharing based on workers' income. However, significant
      obstacles could hinder the effectiveness of emerging cost-sharing strategies,
      including inadequate information on quality of care and provider resistance.

PMID- 14976992
TI  - For-profit conversion and merger trends among Blue Cross Blue Shield health
      plans.
AB  - Blue Cross and Blue Shield (BCBS) health plans, which insure nearly one in three
      Americans, historically have operated as local, nonprofit or mutual
      organizations. However, since the mid-1990s, BCBS plans increasingly have
      converted to for-profit companies and merged with Blue plans in other states.
      State insurance regulators, charged with weighing the costs and benefits of
      conversions and mergers to consumers, often wrestle with the legal complexities
      of these deals, according to Center for Studying Health System Change (HSC) site
      visits to 12 nationally representative communities. Although state regulatory
      scrutiny has slowed the pace of conversions recently, conversion activity is
      likely to accelerate again as the political and regulatory landscapes shift and
      plans adapt conversion strategies. The limited evidence available from HSC site
      visits and conversion proceedings suggests that conversions and mergers have had
      neither significant negative nor positive effects on consumers.

PMID- 14976993
TI  - Dimensions of publicness and performance in substance abuse treatment
      organizations.
AB  - Changes in funding, clientele, and treatment practices of public and privately
      owned substance abuse treatment programs, compelled in part by increased cost
      containment pressures, have prompted researchers' investigations of the
      implications of organizational form for treatment programs. These studies
      primarily probe associations between ownership status, patient characteristics,
      and services delivered and do not empirically link organizational form or
      structure to treatment outcomes. Data from the National Treatment Improvement
      Evaluation Study (NTIES) were used to study the relationship of ownership and
      other dimensions of publicness identified in the public management literature to
      patient outcomes, controlling for patient characteristics, treatment experiences,
      and other program characteristics. A few effects of organizational form and
      structure on substance abuse treatment outcomes are statistically significant
      (primarily improved social functioning), although the specific contributions of
      measures of ownership and publicness to explaining program-level variation are
      generally small.

PMID- 14976994
TI  - Fit to be tied. New gowns provide higher patient satisfaction.

PMID- 14976995
TI  - The gravity of LBNP exercise: preliminary lessons learned from identical twins in
      bed for 30 days.

PMID- 14976996
TI  - Head down tilt combined with breathing assistance by the "IRON LUNG." A new
      simulation model for cardiovascular deconditioning, skin, and kidney function in
      weightlessness?
AB  - In 1951 Gauer, Henry and Sieker proposed that "central hyper-volemia" might
      produce a diuresis that serves to reduce blood volume, a postulated negative
      feedback system for the control of blood volume. Recent surprising results from
      human spaceflight indicate that although a central hyper-volemia takes place in
      weightlessness, an increase in salt and urine excretion cannot be observed. We
      hypothesised that on earth the mediastinum is shaped by gravity because of the
      gravity dependent hydrostatic gradient in the blood filled cavities and that its
      unloading by weightlessness reduces the wall stretch in the atria, thus resulting
      in reduced sodium and urine excretion. Therefore we have applied the principle of
      the "Iron Lung" (lung pressure manipulator LPM) in combination with a simulation
      method of weightlessness, head down tilt bed rest (HDT), to test this hypothesis.
      We found that similar to weightlessness, not only urinary excretion, but also
      evaporative water loss was reduced and that diastolic blood pressure increased.

PMID- 14976997
TI  - Influence of otoliths and neck muscle receptors on peripheral hemodynamic
      regulation.
AB  - To evaluate the cardiovascular changes induced by otoliths and neck
      mechanoreceptors stimulation during head movements, nine subjects in supine prone
      position performed passive head-down neck flexion (P.Ext) and head up P.Extension
      (P.Flex) As the lower limbs vasoconstricted from P.Ext to P.Flex, it is suggested
      that the otoliths stimulation towards the base of the head (like in standing
      position) contribute to reduce the vasoconstriction whereas when stimulated
      towards the top of the head (head flexion) they increase it.

PMID- 14976998
TI  - Comparing cardiovascular responses during exercise between head-down tilt
      pedaling with lower body negative pressure and upright cycling in man.
AB  - If lower body negative pressure (LBNP) loaded on exercise in weightlessness
      environment is able to derive a comparable cardiovascular responses to these in
      the ground, it should be identified as an optimal LBNP for exercise in space. To
      investigate the LBNP, 7 young subjects were exercised 4 work rates stepping up
      every 50 watts from 50 watts to 200 watts every 5 minutes in the upright position
      or 6 degree head down tilt position with each LBNP of 20, 40, 60, 80, and 100
      mmHg. Oxygen uptake during tilt exercise with over 60 mmHg LBNP was not different
      from it in upright exercise. Heart rate and systolic arterial pressure responses
      to exercise were very similar between tilt exercise with 60 mmHg LBNP and upright
      exercise. In conclusion, the optimal LBNP loaded on exercise in space should be
      around 60 mmHg.

PMID- 14976999
TI  - Optimizing an LBNP protocol to test cardiopulmonary and arterial baroreflex
      control of vascular resistance.

PMID- 14977000
TI  - Venous stagnation induced by 7 days in HDT, in the cerebral, ophthalmic, renal
      and splanchnic territories.
AB  - The scientific objectives was to quantify the vascular changes in the brain, eye
      fundus, renal parenchyma, and splanchnic network. Heart, portal, jugular, femoral
      veins were investigate by Echography. The cerebral mesenteric, renal and
      ophthalmic arteries were investigated by Doppler. Eye fundus vein an papilla were
      investigated by optical video eye fundus. The left ventricle volume decreased as
      usual in HDT. The cerebral and ophthalmic vascular resistances didn't change
      whereas the eye fundus papilla and vein, and the jugular vein increased. These
      arterial and venous data confirm the existence of cephalic venous blood stasis
      without sign of intracranial hypertension. On the other hand the kidney volume
      increased which is in agreement with blood flow stagnation at this level. At last
      the mesenteric vascular resistance decreased and the portal vein section
      increased in HDT which is in favor of an increase in flow and flow volume through
      the splanchnic area.

PMID- 14977001
TI  - Dynamics of blood pressure, pulse wave transit time and systolic time intervals
      during acute gravity changes induced by parabolic flight.
AB  - To investigate cardiovascular adaptation to transient microgravity
      (microgravity), we measured RR intervals (RRI), arterial blood pressure (BP),
      pulse wave transit time (PTT) and systolic time intervals (STI) during parabolic
      flight. Our results demonstrate that during microgram RRI, BP and PTT are subject
      to a rapid adaptation likely mediated by the baroreflex whereas STI changes with
      microgravity but does not present further adaptation.

PMID- 14977002
TI  - Responses of sympathoadrenal and renin angiotensin systems to stress stimuli in
      humans during real and simulated microgravity.
AB  - Changes of plasma hormone levels were investigated in human subjects after
      exposure to physical exercise (WL) and insulin induced hypoglycemia (ITT) during
      space flight or after head down bed rest (HDBR). Exaggerated responses of plasma
      epinephrine (EPI), norepinephrine (NE) and aldosterone (ALD) were observed after
      WL during space flight as compared to preflight response. Hypoglycemia during
      space flight induced attenuated responses of EPI, NE and augmented response of
      ALD. Exposure to WL during HDBR was followed by significantly exaggerated
      responses of plasma EPI, NE, ALD, PRA and cortisol. In HDBR the responses of
      plasma EPI, NE and cortisol were reduced and PRA response was exaggerated during
      ITT. These data indicate that hormonal responses to ITT and WL are similar at
      real and simulated microgravity.

PMID- 14977003
TI  - Effect of simulated weightlessness on pressure-volume relationships of femoral
      veins in vivo of New-Zealand rabbits.
AB  - OBJECTIVES: To observe the change of pressure-volume relationships of femoral
      veins of rabbits after simulated weightlessness. METHODS: Head-down tilt(HDT) -20
      degrees rabbit model was used to simulate weightlessness .24 healthy male New
      Zealand Rabbits were randomly divided into 21d HDT group, 10d HDT group and
      control group, with 8 in each. The pressure-volume relationships of rabbits
      femoral veins were measured. RESULT: The femoral vein P-V relationship curves of
      HDT groups were shifted to larger volume change ratio than that of control group.
      The P-V relationship curve of the 21d HDT group was shifted more obviously than
      that of HDT-10d. B1 and B2 in quadratic equations of 21d HDT group were
      significantly higher than these value of 10d HDT group and control group during
      expansion (inflow) and collapse (outflow) (P<0.01). CONCLUSIONS: The femoral
      venous compliance increased after weightlessness simulation and the femoral
      venous compliance of 21d-HDT increased more obviously than that of 10d-HDT.

PMID- 14977004
TI  - [Three dimensional structure analysis of organic chemical compounds from natural
      sources using NMR spectral analysis].

PMID- 14977005
TI  - [Molecular model of A-ring modified vitamin D bound to VDR].

PMID- 14977006
TI  - [Antioxidant and anti-allergic effects of polyphenols].

PMID- 14977007
TI  - [Metabolism of polyphenols in rats].

PMID- 14977008
TI  - [Relationship between structure of chemical substances and their affinity to
      estrogen receptors].

PMID- 14977009
TI  - [Overexpression of NP95mRNA by tumor promoters in the promotion phase of two
      stage BALB/3T3 cell transformation assay].

PMID- 14977010
TI  - [Safety evaluation of chemicals by proteome analysis of rat embryos in early
      phase nidation].

PMID- 14977011
TI  - [Safety evaluation of chemicals by their effect on mRNA levels of the factors
      participating in the decomposition of liver extracellular matrix].

PMID- 14977012
TI  - [Safety evaluation of metallic biocompatible materials by their effect on cell
      differentiation of human osteoblasts].

PMID- 14977013
TI  - [Safety evaluation of drugs on the cardiovascular system by the analysis of gene
      expression].

PMID- 14977014
TI  - [Safety evaluation of chemicals by the analysis of gene expression in cell cycle
      proteins].

PMID- 14977015
TI  - [Genes regulating the cytotoxic effect of inflammatory cytokines on cultured
      keratinocytes of mice].

PMID- 14977016
TI  - [Cytokine and chemokine gene expressions as makers of chemically induced
      allergies].

PMID- 14977017
TI  - [Development of a gene expression profiling system for safety evaluation of
      chemicals].

PMID- 14977018
TI  - [Safety evaluation of chemicals using bibliographic databases for their effects
      on gene expression profiles].

PMID- 14977019
TI  - Evaluating the quality of sexual health care provided to adolescents in medicaid
      managed care: a comparison of two data sources.
AB  - This study compares 2 data sources to evaluate the quality of sexual health care
      provided to adolescents in Medicaid managed care: (a) Medicaid encounter data and
      (b) medical record data. Data from 1998 for 1112 adolescent enrollees came from 3
      Seattle-area managed care organizations (MCOs): a group model health maintenance
      organization, an independent practice association, and a clinic network. Quality
      of care was tracked by estimating within-MCO chlamydia testing rates for sexually
      active female enrollees. Rates varied dramatically depending on which data source
      was used. Logistic regression models indicated substantially less difference
      between MCOs when analysis was based on data from the 2 sources combined than
      when based on either data source alone. Study results did not support the use of
      Medicaid encounter data as a sole data source for evaluating quality of
      adolescent sexual health care, despite the cost savings this would represent.
      However, encounter data, used as an adjunct to medical record review, may
      increase the reliability of quality evaluations.

PMID- 14977020
TI  - Variations in diabetes care and the influence of office systems.
AB  - Although a variety of office tools have been shown to improve diabetes care, the
      use and effectiveness of these tools outside the context of clinical trials is
      largely unknown. We surveyed primary care practices in Kansas. Using Medicare
      claims, we identified patients with diabetes, linked them to practices, and
      assessed the use of glycohemoglobin (GHb) tests, eye examinations, and lipid
      profiles. Performance rates among practices ranged from 15% to 100% (mean = 84%)
      for GHb tests, 20% to 100% (mean = 70%) for lipid profiles, and 50% to 100% (mean
      = 78%) for eye examinations. None of the practices used computerized tracking
      systems, 29% used diabetes flowsheets, and 33% allocated specific diabetes care
      responsibilities to nonphysician personnel. Neither use of flowsheets nor use of
      nonphysician personnel was associated with improvements in diabetes care.
      Although practices varied widely in their care of patients with diabetes, as
      currently implemented, office system tools have not led to consistently better
      performance.

PMID- 14977021
TI  - Quality of care for hypertension and diabetes in federal- versus commercial
      managed care organizations.
AB  - Initiatives to improve quality in primary care include use of performance
      measures to benchmark health care organizations. We looked for an objective way
      to compare primary care quality in the Veterans Affairs (VA) with that of private
      sector. We analyzed performance measures of the Health Plan and Employer Data
      Information Set (HEDIS) used in ambulatory care for hypertension and diabetes and
      compared a sample data from a network of VA hospitals with those from National
      Committee for Quality Assurance's The State of Health Care Quality 2002 Report.
      The VA data were comparable to the national data. Performance on the hypertension
      control measure was slightly below the HEDIS national average but better than the
      regional commercial average. VA's performance on all diabetes measures was
      higher. Although the VA network had a large influx in patient base recently, the
      quality of outpatient care in hypertension and diabetes as measured by
      standardized performance indicators in the network compared favorably with
      commercial Health Maintenance Organizations in the private sector.

PMID- 14977022
TI  - Commentary: quality improvement projects: how do we protect patients' rights?
AB  - A recent ruling by the Office of Human Research Protection (OHRP) has renewed an
      ongoing debate over whether Institutional Review Boards (IRBs) should have
      oversight not only over clinical research but also over quality improvement
      projects (QIPs). The authors discussed the similarities and differences among
      clinical practice, QIPs, and clinical research, pointing out issues to consider
      when identifying the most appropriate method for QIP oversight and
      accountability. They note that potential solutions must address ethical issues
      (eg, patient safety, privacy, and self-determination) and weigh the effect of the
      underlying QIP goal (administrative versus clinical improvement) on an individual
      patient and patient populations. They conclude that because QIPs are an extension
      of clinical practice and have elements of clinical research, it too should have
      an oversight system. Institutional or regional quality improvement boards,
      operating parallel to current IRBs, are suggested as 1 means of ensuring that QIP
      participants are offered the same protections as those who take part in clinical
      research.

PMID- 14977023
TI  - Depression management in medical clinics: does healthcare sector make a
      difference?
AB  - Medical providers often fail to treat depression. We examined whether treatment
      is more aggressive in a setting with accessible mental health resources, the
      Veterans Health Administration (VA). VA and non-VA primary care physicians and
      medical specialists viewed a videotape vignette portraying a patient meeting
      criteria for major depression and then answered interviewer-administered
      questions about management. We found that 24% of VA versus 15% of non-VA
      physicians would initiate guideline-recommended treatment (antidepressants or
      mental health referral, or both) (P = .09). Among those who identified depression
      as likely, 42% of VA versus 19% of non-VA physicians would treat (P = .002): 23%
      versus 3% recommended mental health referral (P < .001) and 21% versus 17% an
      antidepressant (P = .67). Although many patients with major depression may not
      receive guideline-recommended management, VA physicians do initiate mental health
      referral more often than do non-VA physicians. Access to mental health services
      may prove valuable in the campaign to increase physician adherence to depression
      clinical guidelines.

PMID- 14977024
TI  - Benefit coverage of novel antipsychotics in Medicaid programs and the Veterans
      Health Administration.
AB  - When risperidone, olanzapine, and quetiapine were introduced, concerns were
      raised regarding the extent to which drug benefit policies might constrain their
      use. A national survey of eligible Medicaid programs (N = 47; 100%) and Veterans
      Health Administration facilities (N = 141; 94%) in 1998 found that within
      Medicaid, open formularies were common, preauthorization requirements were rare,
      and few barriers existed, whereas VHA facilities reported relatively more
      constraints in terms of formulary restrictions and preauthorization requirements.
      Although drug benefit policies have the potential to exert a major influence over
      prescribing practices, it is unlikely that these policies significantly
      restricted access to these antipsychotics.

PMID- 14977025
TI  - Perceptual evaluation of motor speech following treatment for childhood
      cerebellar tumour.
AB  - The speech characteristics, oromotor function and speech intelligibility of a
      group of children treated for cerebellar tumour (CT) was investigated
      perceptually. Assessment of these areas was performed on 11 children treated for
      CT with dysarthric speech as well as 21 non-neurologically impaired controls
      matched for age and sex to obtain a comprehensive perceptual profile of their
      speech and oromotor mechanism. Contributing to the perception of dysarthria were
      a number of deviant speech dimensions including imprecision of consonants,
      hoarseness and decreased pitch variation, as well as a reduction in overall
      speech intelligibility for both sentences and connected speech. Oromotor
      assessment revealed deficits in lip, tongue and laryngeal function, particularly
      relating to deficits in timing and coordination of movements. The most salient
      features of the dysarthria seen in children treated for CT were the mild nature
      of the speech disorder and clustering of speech deficits in the prosodic,
      phonatory and articulatory aspects of speech production.

PMID- 14977026
TI  - Phonological development: a normative study of British English-speaking children.
AB  - This paper reports a normative study on the phonological development of British
      English-speaking children. Speech samples of 684 children, aged between 3;0 and
      6;11 years, randomly selected from nurseries and schools in eight different areas
      throughout the UK, were collected and analysed to obtain normative data. This
      paper reports on two aspects of speech development: the age of acquisition of
      sounds (phonetic acquisition) and the age that error patterns were suppressed
      (phonemic acquisition). It discusses the effects of age, gender and socio
      economic status on speech sound development. The study found that older children
      had more accurate production and fewer error patterns in their speech. It found
      no gender differences in the younger age groups. However, in the oldest age
      group, it found the phonological accuracy measures of girls' better than boys. It
      found no significant effects of socio-economic status on any of the phonological
      accuracy measures.

PMID- 14977027
TI  - A foot domain account of prosodically-conditioned substitutions.
AB  - Children's prosodically conditioned substitutions have been recently described in
      terms of syllable structure. In this paper we present an alternative analysis,
      based on the position of the consonant within the foot. We review data from a
      previous case study (Chiat, 1989) that provide evidence in favour of a foot
      domain account and against the syllable structure account. One consequence of
      this finding is that it may be unnecessary to postulate that intervocalic
      consonants are captured into the coda of the previous syllable. While we caution
      that more evidence is needed to further test the foot and syllable accounts, we
      suggest that the foot be considered as a locus of substitution errors in
      phonology-disordered children.

PMID- 14977028
TI  - Within-session rates of responding when reinforcer magnitude is changed within
      the session.
AB  - In the present experiment, the authors investigated the idea that within-session
      changes in operant response rates occur because subjects sensitize and then
      habituate to the reinforcer. If that is true, then altering an aspect of the
      reinforcer within the session should alter the observed within-session
      responding. The authors tested that idea by having rats press a lever for 2 food
      pellet reinforcers delivered by a variable-interval 120-s schedule during 60-min
      baseline sessions. In treatment conditions, the magnitude of the reinforcer was
      halved (1 pellet) or doubled (4 pellets) 10, 20, 30, 40, or 50 min into the
      session. That magnitude of reinforcement then remained in effect for the rest of
      the session. Altering reinforcer magnitude altered the rates of responding within
      the session in a fashion consistent with the habituation explanation, that is,
      response rates increased, relative to baseline, when the magnitude of
      reinforcement was increased. They decreased when the magnitude was decreased.
      Those results were seemingly inconsistent with the competing idea that within
      session decreases in responding rates are produced by satiation.

PMID- 14977029
TI  - Time-pressure effects on performance in a base-rate task.
AB  - Researchers assume that time pressure impairs performance in decision tasks by
      invoking heuristic processes. In the present study, the authors inquired (a)
      whether it was possible in some cases for time pressure to improve performance or
      to alter it without impairing it, and (b) whether the heuristic invoked by base
      rate neglect under direct experience can be identified. They used a probability
      learning design in 2 experiments, and they measured the choice proportions after
      each of 2 possible cues in each experiment. In 1 comparison, time pressure
      increased predictions of the more likely outcome, which improved performance. In
      2 comparisons, time pressure changed the choice proportions without affecting
      performance. In a 4th comparison, time pressure hindered performance. The choice
      proportions were consistent with heuristic processing that is based on cue
      matching rather than on cue accuracy, base rates, or posterior probabilities.

PMID- 14977030
TI  - Examination of psychiatric symptoms in student athletes.
AB  - In the present study, the authors examined the severity of psychiatric symptoms
      in undergraduate recreational (noncompetitive) athletes (n = 64) and National
      Collegiate Athletic Association (NCAA; competitive) athletes (n = 72). The
      results indicated that the 2 groups were similar in the severity of psychiatric
      symptoms. The recreational and NCAA athletes combined (n = 136) showed less
      severe global psychiatric symptoms when they were compared with an undergraduate
      control group (n = 435). The implications of the study are discussed in the
      context of those findings.

PMID- 14977031
TI  - Body asymmetry affects conjugate lateral eye movement.
AB  - A. H. Baker (1989) and A. H. Baker and A. I. Ledner (1990) reported that
      asymmetrical visual stimulation affects conjugate lateral eye movement (CLEM). In
      the present article, the authors explored whether asymmetrical body position
      similarly affects CLEM. The authors assessed CLEMs twice in a counterbalanced
      design. In the control (symmetric) condition, each participant sat in a
      completely symmetrical position facing a wall devoid of any asymmetrical
      features. In the experimental (asymmetrical) condition, half the participants
      rotated their heads 68 degrees clockwise relative to their bodies to face the
      experimenter, and the other half rotated their heads 68 degrees counterclockwise,
      also to face the experimenter. CLEM was predominantly toward the body's position
      in the asymmetrical condition rather than toward the body's position in the
      symmetrical condition.

PMID- 14977032
TI  - Effects of outside issues on the comparison question test.
AB  - In the present study, the authors examined the effects of outside issues on the
      validity of the Comparison Question Test in a laboratory mock-crime paradigm. In
      a 2 x 2 x 2 factorial design, 192 participants either did or did not commit (a) a
      mock theft of a dollar (about which they were tested), or (b) a mock theft of
      dollars 20 (the outside issue); and they either were or were not asked questions
      about an outside issue. The presence of the outside issue had a strong
      differential impact on the participants who were innocent of the tested issue,
      and it dramatically moved their scores toward deception. The impact of an outside
      issue on the guilty was minimal. Test questions about possible outside issues
      were ineffective in detecting the presence of the outside issue, but they did
      function as comparison questions. The results have implications for understanding
      the high rate of false positive outcomes in some studies.

PMID- 14977033
TI  - The difference between t and z and the difference it makes.
AB  - Tests of the null hypothesis for comparisons involving sample means use the t
      test when the conditions of the z test cannot be met. The 2 tests have different
      rationales and can lead to different conclusions regarding significance. In the
      present study, the authors compared the properties of t and z in simulation runs.
      The differences in the results are a result of fluctuations in the t test sample
      variances that do not exist in the z test, and those differences lead to
      differences in designating the significance of comparisons.

PMID- 14977034
TI  - The development of expertise: animal models?
AB  - There is a continuing debate in the psychological literature between researchers
      who lean more toward learning theories of expertise development and those who
      lean more toward talent theories. However, the development of human expertise has
      not been open to direct experimental methods and will probably continue to elude
      experimentalists in the future. A promising alternative to direct experimental
      methods is to use human animal models, a possibility that researchers in
      expertise seem to have overlooked. However, there are studies in the animal
      behavior literature that address the development of nonhuman animal expertise
      without specifically referring to the topic as expertise. In the present study,
      the author discusses two nonhuman animal examples of expertise development that
      have been researched by ethologists. Nonhuman animal expertise development,
      unlike human expertise development, is subject to direct experimentation. The
      author thus recommends that researchers use nonhuman animals in their studies of
      expertise.

PMID- 14977035
TI  - The quality-value proposition in health care.
AB  - Powerful forces are converging in US health care to finally cause recognition of
      the inherently logical relationship between quality and money. The forces, or
      marketplace "drivers," which are converging to compel recognition of the
      relationship between cost and quality are: (1) the increasing costs of care; (2)
      the recurrence of another medical malpractice crisis; and (3) the recognition
      inside and outside of health care that quality is inconsistent and unacceptable.
      It is apparent that hospital administrators, financial officers, board members,
      and medical staff leadership do not routinely do two things: (1) relate quality
      to finance; and (2) appreciate the intra-hospital structural problems that impede
      quality attainment. This article discusses these factors and offers a positive
      method for re-structuring quality efforts and focusing the hospital and its
      medical staff on quality. The simple but compelling thesis of the authors is that
      health care must immediately engage in the transformation to making quality of
      medical care the fundamental business strategy of the organization.

PMID- 14977036
TI  - Hidden costs in the physician-insurer relationship.
AB  - Numerous reports document the frictions in health care funding systems,
      particularly related to the physician-insurer dyad. Efforts to improve efficient
      patient care by improving interactions between the physician and insurer are
      ongoing. This article examines one dimension--relationship quality--and
      demonstrates how attention to building commitment and trust within the
      relationship has financial benefits. Using a survey of physician practice
      personnel, commitment and trust are shown to have a positive influence on
      financial performance metrics. Commitment and trust antecedents are empirically
      documented. These antecedents provide a starting point for physician practices
      seeking to enhance their insurer relationships as a mechanism for improved
      operations.

PMID- 14977037
TI  - A process evaluation of a health care Balanced Scorecard.
AB  - The purpose of this study was to assess a Balanced Scorecard (BSC) process in
      health care. Specifically, this study evaluated how a BSC was implemented by the
      emergency medicine service line within one integrated delivery system (IDS). The
      study compared the BSC definition process used by the service line with the
      definition process that is recommended by the originators of the BSC. Also, the
      maturity of the service line's BSC production process was assessed using IBM's
      business process evaluation methodology. In comparing the service line's BSC
      approach to the BSC originators' three phases of a BSC, the service line was
      found to follow the protocol, with the exception of Phase One. The service line's
      BSC process, overall, received a "beginner" rating. It is recommended that
      practitioners and researchers consider using the checklist that was developed and
      used in this study for process certification of a BSC. In addition, a
      questionnaire is provided for use in future BSC evaluations within the health
      care industry.

PMID- 14977038
TI  - Ban or regulate? Costs of dental occupational safety from mercury.
AB  - Occupational hazard from mercury (Hg) exposure in the dental practice is less
      well studied than patient and environmental hazard. Developing country evidence
      on all dimensions of the problem is sparse, as are analyses of cost tradeoffs
      from practices that can reduce Hg exposure. A survey was conducted on 99 dentists
      from Greater Beirut to investigate levels of exposure and factors affecting them.
      Twenty-five percent of the dentists had hair Hg concentrations above the
      initially accepted level of 5 microg/g, and 28 percent had levels exceeding 10
      microg/g. Gloves and masks had the most significant effect on the reduction of Hg
      level. Given these results and drawing on previous literature, we estimate and
      compare the costs of a total ban on amalgam use versus regulatory interventions
      to reduce exposure. We conclude that regulation constitutes a significantly lower
      financial burden. This result is consistent with policy conclusions in most
      industrialized countries. In addition, it serves as a useful benchmark for
      developing countries with dental sector and socioeconomic characteristics similar
      to those of Lebanon, such as a range of countries in Latin America, Eastern
      Europe, Asia, and Africa.

PMID- 14977039
TI  - Do nonprofit HMOs eliminate racial disparities in cardiac care?
AB  - African-Americans have far less access to treatment for heart disease than
      similar white Americans. In this article, we explore the sector difference theory
      hypothesis that treatment provided by a nonprofit Medicaid managed care plan can
      reduce or even eliminate the race gap. Specifically, we compare the treatment
      offered to patients in for-profit Medicaid managed care programs to the treatment
      offered to similar patients in nonprofit Medicaid managed care programs. Data are
      from the Maryland Health Services Cost Review Commission and cover all patients
      discharged from hospitals in Maryland during calendar year 1998 with principal
      diagnoses indicating diseases of the circulatory system (ICD-9-CM codes 390
      through 459) or chest pain (ICD-9-CM codes 786.50 through 786.52 and code
      786.59). African-Americans were significantly less likely to receive the three
      treatments of interest, even after controlling for principal diagnosis, blood
      pressure, co-morbidities, and age. In regard to African-American access to
      treatment, there were no significant differences between the sectors.

PMID- 14977040
TI  - The chemistry of nitrosative stress induced by nitric oxide and reactive nitrogen
      oxide species. Putting perspective on stressful biological situations.
AB  - This review addresses many of the chemical aspects of nitrosative stress mediated
      by N2O3. From a cellular perspective, N2O3 and the resulting reactive nitrogen
      oxide species target specific motifs such as thiols, lysine active sites, and
      zinc fingers and is dependant upon both the rates of production as well as
      consumption of NO and must be taken into account in order to access the
      nitrosative environment. Since production and consumption are integral parts of
      N2O3 generation, we predict that nitrosative stress occurs under specific
      conditions, such as chronic inflammation. In contrast to conditions of stress,
      nitrosative chemistry may also provide cellular protection through the regulation
      of critical signaling pathways. Therefore, a careful evaluation of the chemistry
      of nitrosation based upon specific experimental conditions may provide a better
      understanding of how the subtle balance between oxidative and nitrosative stress
      may be involved in the etiology and control of various disease processes.

PMID- 14977041
TI  - 'Til cell death do us part: nitric oxide and mechanisms of hepatotoxicity.
AB  - Like many juggernauts in biology, the elusive nature of nitric oxide (NO) sprints
      through the fields, sometimes the savior, at other times the scimitar. In the
      liver, which is the metabolic center of the organism, hepatocytes and immune
      cells trade blows using the reactive diatomic molecule NO to induce cellular
      damage under toxic conditions. In response, hepatocytes can utilize several
      mechanisms of NO to their protective advantage by prohibiting the activation of
      programmed cell death, a.k.a. apoptosis. The balance of these effects in this
      reactive milieu set the stage for the homeostatic response to cellular injury
      that determines whether hepatocytes will live, die, or regenerate. Insights that
      we and others have gained from the liver under pathologic conditions of stress
      can be applied to the understanding of cellular death mechanisms in other organs
      and tissues.

PMID- 14977042
TI  - Singlet oxygen-mediated damage to cellular DNA determined by the comet assay
      associated with DNA repair enzymes.
AB  - The damage profile produced by the reaction of singlet molecular oxygen with
      cellular DNA was determined using the comet assay associated with DNA repair
      enzymes. Singlet oxygen was produced intracellularly by thermal decomposition of
      a water-soluble endoperoxide of a naphthalene derivative which is able to
      penetrate through the membrane into mammalian cells. We found that the DNA
      modifications produced by singlet oxygen were almost exclusively oxidised purines
      recognised by the formamidopyrimidine DNA N-glycosylase. In contrast, significant
      amounts of direct strand breaks and alkali-labile sites or oxidised pyrimidines,
      detectable by the bacterial endonuclease III, were not produced.

PMID- 14977043
TI  - Functional studies on the ligand-binding domain of Ultraspiracle from Drosophila
      melanogaster.
AB  - The functional insect ecdysteroid receptor is comprised of the ecdysone receptor
      (EcR) and Ultraspiracle (USP). The ligand-binding domain (LBD) of USP was fused
      to the GAL4 DNA-binding domain (GAL4-DBD) and characterized by analyzing the
      effect of site-directed mutations in the LBD. Normal and mutant proteins were
      tested for ligand and DNA binding, dimerization, and their ability to induce gene
      expression. The presence of helix 12 proved to be essential for DNA binding and
      was necessary to confer efficient ecdysteroid binding to the heterodimer with the
      EcR (LBD), but did not influence dimerization. The antagonistic position of helix
      12 is indispensible for interaction between the fusion protein and DNA, whereas
      hormone binding to the EcR (LBD) was only partially reduced if fixation of helix
      12 was disturbed. The mutation of amino acids, which presumably bind to a fatty
      acid evoked a profound negative influence on transactivation ability, although
      enhanced transactivation potency and ligand binding to the ecdysteroid receptor
      was impaired to varying degrees by mutation of these residues. Mutations of one
      fatty acid-binding residue within the ligand-binding pocket, 1323, however,
      evoked enhanced transactivation. The results confirmed that the LBD of
      Ultraspiracle modifies ecdysteroid receptor function through intermolecular
      interactions and demonstrated that the ligand-binding pocket of USP modifies the
      DNA-binding and transactivation abilities of the fusion protein.

PMID- 14977044
TI  - Structural destabilization of the recombinant thermophilic TthL11 ribosomal
      protein by a single amino acid substitution.
AB  - Thermus thermophilus L11 protein has previously been reported to be resistant
      against tryptic and chymotryptic proteolysis under native conditions. With a
      single amino acid substitution, namely Trp101Arg, conformational changes were
      induced that resulted in the exhibition of specific amino acids that served as
      targets for tryptic and chymotryptic action and rendered the protein highly
      unstable even during purification. This unexpected process was evidenced by the
      isolation with size exclusion gel chromatography of the well-structured
      chymotryptic N-terminal domain in a high amount and its characterization both by
      Edman degradation and QTOF-EMS spectroscopy. On the other hand, the substitution
      of Val38Cys, which did not contribute to structural changes, indicates a very
      possible implication of this amino acid in the protein methylation process. The
      data reported in this work illustrate the distinctive amino acid dynamics in a
      thermophilic protein, which, while serving the function common to its
      counterparts from mesophilic organisms, has had to adapt to the extreme
      environmental conditions typical of thermophilic organisms.

PMID- 14977045
TI  - Relevance of the kinetic equilibrium of forces to the control of the cell cycle
      by Ras proteins.
AB  - In higher organisms, the replacement of GDP bound to Ras proteins with GTP, under
      the participation of an exchange factor, is an important step in the initiation
      of cell division. Ras-GTP activates kinases and other effectors, which pass
      signals to the cell nucleus and to the cytoskeleton. The active state of Ras is
      terminated by hydrolysis of the bound GTP with the assistance of an activating
      protein (GAP). Knowledge of these regulatory events is based on extensive
      experimental data, but many aspects of their interpretation are still
      controversial. It is assumed here that a significant part of the free energy
      released when two partners associate is stored in a 'kinetic equilibrium of
      forces' (KEF), and used to facilitate the separation from a third partner. The
      activation of the Raf kinase is explained primarily in terms of an allosteric
      effect of Ras-GTP on the phosphate transfer in the catalytic region of the
      kinase. A mechanism is proposed for the modification of GAP by Ras-GTP, which is
      believed to be a prerequisite for the well-known crosstalk between the Ras- and
      Rho-dependent signalling pathways. The cell, by meeting the requirements for KEF,
      manages to reduce activation barriers, thus significantly accelerating the
      regulatory events and other complex biological reaction sequences.

PMID- 14977046
TI  - N-linked glycosylation of the human bradykinin B2 receptor is required for
      optimal cell-surface expression and coupling.
AB  - To investigate the glycosylation of the human bradykinin B2 receptor and the
      functional significance of this modification, we studied receptors mutated at
      single or multiple combinations of the three potential N-linked glycosylation
      sites, asparagines N3, N12 and N180, in COS-7, HEK 293 and CHO-K1 cells. Western
      blot experiments demonstrated that all three extracellular asparagines are
      glycosylated. The kinetics of bradykinin binding and receptor sequestration
      remained unchanged after glycosylation had been suppressed. However, the
      glycosylated receptors were expressed at the cell-surface to a much greater
      extent than the non-glycosylated receptor and coupling to phospholipase C was
      less efficient for receptor lacking N-terminal glycosylation. These results
      indicate that, for the human bradykinin B2 receptor, glycosylation is not
      required for optimal ligand binding, but plays an important role in cell-surface
      addressing and receptor function.

PMID- 14977047
TI  - Identification of sialic acids on Leishmania donovani amastigotes.
AB  - The presence of Neu5Ac on promastigotes of Leishmania donovani, the causative
      organism of Indian visceral leishmaniasis, has been reported recently. Here we
      report the occurrence of Neu5Ac as a major component on amastigotes, as well as
      Neu5Gc, Neu5,9Ac2 and Neu9Ac5Gc as indicated by fluorimetric high performance
      liquid chromatography and gas liquid chromatography/electron impact mass
      spectrometry. Furthermore, binding studies with Sambucus nigra agglutinin (SNA),
      Maackia amurensis agglutinin (MAA), and various Siglecs, showed the presence of
      both (alpha2 --> 6)- and (alpha2 --> 3)-linked sialic acids; their binding was
      reduced after sialidase pretreatment. Western blotting of amastigote membrane
      glycoproteins with SNA demonstrated the presence of two sialoglycoconjugates of
      Mr values of 164000 and 150000. Similarly, binding of MAA demonstrated the
      presence of five distinct sialoglycans corresponding to molecular masses of 188,
      162, 136, 137 and 124 kDa. Achatinin-H, a lectin that preferentially identifies 9
      O-acetylated sialic acid (alpha2 --> 6)-linked to GalNAc, demonstrated the
      occurrence of two 9-O-acetylated sialoglycans with Mr 158000 and 150000, and was
      corroborated by flow cytometry; this binding was abolished by recombinant 9-O
      acetylesterase pretreatment. Our results indicate that Neu5Ac [(alpha2 --> 6)-
      and (alpha2 --> 3)-linked], as well as Neu5Gc and their 9-O-acetyl derivatives,
      constitute components of the amastigote cell surface of L. donovani.

PMID- 14977048
TI  - Induction of lipoprotein lipase gene expression in Chlamydia pneumoniae-infected
      macrophages is dependent on Ca2+ signaling events.
AB  - Unregulated uptake of low density lipoprotein (LDL) in macrophages is the
      hallmark of early atherogenic lesions, and Chlamydia pneumoniae infection of
      macrophages induces this process by an unknown mechanism. It was therefore aimed
      in this study to investigate (i) the role of C. pneumoniae in macrophage
      expression of the lipoprotein lipase (LpL) gene, (ii) the probable role of Ca2+
      influx signals and (iii) the effect of the process on LDL uptake. Lipoprotein
      lipase mRNA expression and LpL activity in infected RAW-264.7 cells were
      significantly upregulated. A biphasic Ca2+ influx signal was observed in infected
      cells with a moderate influx (303 nM Ca2+) favoring optimal LpL gene expression.
      Also, the antagonists of L-type Ca2+ channel in macrophages significantly down
      regulated LpL gene expression and the biomolecular content of C. pneumoniae
      responsible for the observed events was in part found to be Chlamydia
      lipopolysaccharide (cLPS). Investigations aimed at determining the specific
      relevance of Ca(2+)-dependent lipoprotein lipase gene expression in C. pneumoniae
      infected macrophages showed that the condition caused enhanced uptake of LDL
      which was abrogated by Calphostin-C-mediated down-regulation of LpL. This
      discovery of a specialized Ca2+ influx signal-mediated LpL upregulation in C.
      pneumoniae-infected macrophages provides a mechanistic insight into early events
      involving C. pneumoniae in macrophage foam cell formation resulting from LDL
      uptake.

PMID- 14977049
TI  - Induction of MMP-10 and MMP-1 in a squamous cell carcinoma cell line by
      ultraviolet radiation.
AB  - Ultraviolet radiation may cause non-melanoma skin cancer by genetic and
      epigenetic events. In this study, we investigated in a squamous cell carcinoma
      cell line, SCL-1, whether UV irradiation modulates the expression of matrix
      metalloproteinases, known to be involved in tumor progression and metastasis by
      degradation of extracellular matrix components. UVA or UVB irradiation of SCL-1
      resulted in a rapid transcriptional up-regulation and increased secretion of two
      members of the matrix metalloproteinase family, MMP-10 (stromelysin-2) and MMP-1
      (interstitial collagenase). The increase in MMP-10 steady-state mRNA levels was
      detected 1 hour after UVA and 4 h after UVB irradiation, whereas MMP-1 was
      upregulated 4 h after UVA and 16 h after UVB irradiation of tumor cells. UV
      induced phosphorylation of extracellular regulated kinases (ERK-1/2) and p38
      stress kinase and increased binding of AP-1 transcription factor preceded the
      rapid stimulation of MMPs in SCL-1 cells. Incubation of cells with the MEK1/2
      inhibitor U0126 or the p38 inhibitor SB202190 abolished the UVA and UVB mediated
      induction of MMP-1 and MMP-10. In conclusion, this study shows that UV
      irradiation of squamous cell carcinoma results in a rapid up-regulation of MMPs.
      Our results suggest that the time course of induction of target genes, like MMPs,
      differs between cell types depending on the stimulus.

PMID- 14977050
TI  - Monitoring human parvovirus B19 virus-like particles and antibody complexes in
      solution by fluorescence correlation spectroscopy.
AB  - Fluorescence correlation spectroscopy (FCS) was used in monitoring human
      parvovirus B19 virus-like particle (VLP) antibody complexes from acute phase and
      past-immunity serum samples. The Oregon Green 488-labeled VLPs gave an average
      diffusion coefficient of 1.7 x 10(-7) cm2 s(-1) with an apparent hydrodynamic
      radius of 14 nm. After incubation of the fluorescent VLPs with an acute phase
      serum sample, the mobility information obtained from the fluorescence intensity
      fluctuation by autocorrelation analysis showed an average diffusion coefficient
      of 1.5 x 10(-8) cm2 s(-1), corresponding to an average radius of 157 nm. In
      contrast, incubation of the fluorescent VLPs with a past-immunity serum sample
      gave an average diffusion coefficient of 3.5 x 10(-8) cm2 s(-1) and a radius of
      69 nm. A control serum devoid of B19 antibodies caused a change in the diffusion
      coefficient from 1.7 x 10(-7) to 1.6 x 10(-7) cm2 s(-1), which is much smaller
      than that observed with acute phase or past-immunity sera. Thus, VLP-antibody
      complexes with different diffusion coefficients could be identified for the acute
      phase and past-immunity sera. FCS measurement of VLP-immune complexes could be
      useful in distinguishing between antibodies present in acute phase or past
      immunity sera as well as in titration of the VLPs.

PMID- 14977051
TI  - In vitro folding and characterization of the p53 DNA binding domain.
AB  - The transcription factor p53 acts as major tumor suppressor and is inactivated by
      mutation in more than 50% of all human tumors. We have established an efficient
      procedure for the in vitro folding and purification of the p53 DNA binding domain
      (p53DBD) using a modified factorial matrix approach that supplies large amounts
      of homogeneous (isotope-labeled) p53DBD for application in biochemical,
      crystallographic and NMR spectroscopic studies. We further show with biophysical
      methods that in vitro folded p53DBD is fully functional and that its conformation
      is identical to that obtained from the soluble fraction.

PMID- 14977052
TI  - Innate spatial-temporal reasoning and the identification of genius.
AB  - The teaching of mathematics is invariably language-based, but spatial-temporal
      (ST) reasoning (making a mental image and thinking ahead in space and time) is
      crucial to the understanding of math. Here we report that Big Seed, a demanding
      ST video game, based upon the mathematics of knot theory and previously applied
      to understanding DNA structure and function, can be used to reveal innate ST
      reasoning. Big Seed studies with middle and elementary school children provide
      strong evidence that ST reasoning ability is not only innate but far exceeds
      optimistic expectations based on age, the percentage of children achieving
      exceptional ST performance in less than 7 h of training, and retention of
      ability. A third grader has been identified as a genius (functionally defined) in
      ST performance. Big Seed may be used for training and assessing 'creativity'
      (functionally defined) and ST reasoning as well as discovering genius.

PMID- 14977053
TI  - Deep brain stimulation for movement disorders.
AB  - Movement disorders remain the primary indication for the use of intracranial
      neurostimulation techniques. This review will discuss the history of this
      technology as well as the mechanisms of action, current clinical indications, and
      future prospects for the treatment of movement disorders.

PMID- 14977054
TI  - Neural prostheses for vision: designing a functional interface with retinal
      neurons.
AB  - A number of prevalent eye diseases exist which may lead to partial or total
      blindness, and for which there are currently no cures or means by which to
      restore lost sight. Based on recent progress, it has become apparent that
      artificial prosthetic devices, which would use electrical stimulation of neurons
      in the visual pathway to elicit visual percepts, are likely to some day become a
      viable treatment for patients blinded by these diseases. A number of recent
      scientific reviews have summarized general functional electrical stimulation
      (FES) approaches related to the visual system, and many of the technical
      considerations regarding fabrication, biocompatibility, stimulation thresholds
      and electrotoxicity. This review will address a principal outstanding question in
      retinal prosthesis development: the design and implementation of a functional
      interface with the retina. A functional interface between electrodes and retinal
      neurons will be stable, biocompatible, and will convey useful information to the
      visual system. Several parameters related to both the artificial and biological
      aspects of the interface must be considered; this paper will emphasize electrode
      design. Additional issues central to the development of prosthesis interface
      design, including retinal physiology, eye diseases, and existing animal models of
      retinal degeneration, are also summarized.

PMID- 14977055
TI  - Spatial learning transiently disturbed by intraventricular administration of
      ouabain.
AB  - The presence of sodium-potassium-adenosine triphosphatase (Na+,K+-ATPase) on the
      surface of arachnoid cells indicates that active transport of electrolytes and
      water occurs there. Previously, we accidentally found that intraventricular
      administration of TGF-beta1 impaired rat spatial learning. Levels of Na+,K+ 
      ATPase were decreased in arachnoid cells with fibrosis. To characterize the role
      of the Na+,K+ -ATPase, Wistar rats were intraventricularly administered a total
      of 200 microl of ouabain, at concentrations of 10(-5), 10(-4) and 10(-3) M, for
      one week with an osmotic pump, and were examined with a Morris water maze.
      Latency for reaching the platform did not significantly differ between ouabain
      administered rats and controls. Spatial learning was impaired in a dose-dependent
      manner. Na+,K+ -ATPase activity of arachnoid cells ceased during ouabain
      administration, and recovered completely three weeks after the end of ouabain
      administration. The present results suggest that the Na+,K+ -ATPase on the
      surface of arachnoid cells contributes to maintenance of rat spatial learning.

PMID- 14977056
TI  - Percutaneous vertebroplasty: technique and results in 192 procedures.
AB  - Percutaneous vertebroplasty with acrylic cement (usually polymethylmethacrylate)
      consists of injecting cement into vertebral bodies weakened by osseous lesions.
      The objective of this procedure is to obtain an analgesic effect by mechanical
      stabilization in destructive lesions of the spine. The three major indications
      are aggressive vertebral hemangiomas, severe or refractory pain related to
      osteoporotic vertebral fractures, and malignant vertebral tumors. Complications
      are infrequent, but occur essentially in patients with vertebral malignant
      tumors. We present our experience with 148 patients that underwent 192
      percutaneous PMMA vertebroplasties for the treatment of painful osteoporotic
      compression fractures (76 patients, 105 vertebral levels), hemangiomas (31
      patients, 43 vertebral levels) and neoplasms (31 patients, 43 vertebral levels).
      In a vast majority of appropriately selected cases and especially in osteoporotic
      cases, vertebroplasty constitutes a relatively simple procedure with a very high
      rate of success.

PMID- 14977057
TI  - Does multimodality therapy of arteriovenous malformations improve patient
      outcome?
AB  - The strategy for treating arteriovenous malformations (AVMs) has undergone
      changes and long-term follow-up results remain unclear. To compare the outcomes
      of different treatment strategies, we divided 112 patients with 113 AVMs into
      groups with hemorrhagic (n = 71, 62.8%) and nonhemorrhagic (n = 42, 37.2%) AVMs
      and subdivided these according to the period in which they were treated
      (before/after 1990). In the more recent period, treatment more frequently
      involved the use of the gamma-knife and microembolization to the AVM as well as
      combination therapy. Long-term follow-up showed that the complication rate was
      lower and the Rankin scale better, in the more recently treated group. Based on
      our findings we suggest that AVMs should be treated aggressively using a
      multimodality strategy.

PMID- 14977058
TI  - A neural-network-based detection of epilepsy.
AB  - Diagnosis of epilepsy is primarily based on scalp-recorded electroencephalograms
      (EEG). Unfortunately the long-term recordings obtained from 'ambulatory recording
      systems' contain EEG data of up to one week duration, which has introduced new
      problems for clinical analysis. Traditional methods, where the entire EEG is
      reviewed by a trained professional, are very time-consuming when applied to
      recordings of this length. Therefore, several automated diagnostic aid approaches
      were proposed in recent years, in order to reduce expert effort in analyzing
      lengthy recordings. The most promising approaches to automated diagnosis are
      based on neural networks. This paper describes a method for automated detection
      of epileptic seizures from EEG signals using a multistage nonlinear pre
      processing filter in combination with a diagnostic (LAMSTAR) Artificial Neural
      Network (ANN). Pre-processing via multistage nonlinear filtering, LAMSTAR input
      preparation, ANN training and system performance (1.6% miss rate, 97.2% overall
      accuracy when considering both false-alarms and 'misses') are discussed and are
      shown to compare favorably with earlier approaches presented in recent
      literature.

PMID- 14977059
TI  - Post-operative hematoma after surgery for intracranial meningiomas: causes,
      avoidable risk factors and clinical outcome.
AB  - Intracranial meningiomas are mainly benign lesions amenable for surgical
      resection. However, removal of an intracranial meningioma carries a higher risk
      of post-operative hemorrhage compared to surgery for other intracranial
      neoplasms. Because avoidance of post-operative hematoma is of vital interest for
      neurosurgical patients, the aim of this retrospective study was to analyze risk
      factors of post-operative hematoma associated with meningioma surgery. Two
      hundred and ninety six patients with intracranial meningiomas, operated between
      June 1998 and June 2002, were included in this study. Patients who developed a
      space-occupying post-operative intracranial hemorrhage and were treated
      surgically were identified. Data of patients with and without hematoma were
      retrospectively analyzed to identify risk factors associated with post-operative
      hematoma. Variables analyzed included patients' age, invasion of venous sinus by
      the meningioma, tumor vascularization, arachnoidal infiltration, pre-operative
      prophylaxis of thromboembolic events, peri-operative coagulation abnormalities,
      residual tumor, location and histology of the tumor. Outcome of patients with
      post-operative hematoma was assessed according to the Glasgow Outcome Scale (GOS)
      at discharge and at three months. 21 patients (7.1 %) of 296 patients developed a
      post-operative intracranial hematoma requiring surgical evacuation. Age was
      significantly higher in the hematoma group 62.4 +/- 14.0 years compared to
      patients without post-operative hematoma 56.1 +/- 12.0 (p < 0.05; t-test).
      Patients older than 70 years had a six-fold increased risk to develop a post
      operative hematoma (Chi2 test, 95% CI 1.949-13.224). Patients with post-operative
      hemorrhage had significant lower post-operative prothrombin time, fibrinogen and
      platelets immediately after surgery and lower platelets at day 1. None of the
      other parameters, including pre-operative routine coagulation values, differed
      significantly between patients with and without post-operative hemorrhage. Three
      patients with post-operative hematoma showed platelet dysfunction and three
      patients showed decreased FXIII activity. Of those patients with post-operative
      hemorrhage at three months follow up three patients (13%) succumbed from reasons
      not directly related to hemorrhage, one patient remained GOS 2 (4.3%), four
      patients (17.4%) were GOS 3 and 15 (65.4%) patients had favorable outcome (GOS 4
      [one patient] and GOS5 [14 patients]). Meningioma surgery carries a higher risk
      for post-operative hematoma in the elderly. Thrombocytopenia and other hemostatic
      disorders were frequently associated with post-operative hemorrhage after
      meningioma surgery, while no surgical factors could be defined. Extending
      coagulation tests and specific replacement therapy may prevent hematoma formation
      and improve the patients outcome.

PMID- 14977060
TI  - Multidisciplinary treatment of posterior circulation ischemia.
AB  - Compromise of blood flow to the brain leads to cerebral ischemia, which if left
      untreated may even result in cerebral infarction. This has been the main cause of
      major morbidity and mortality over the years in the US and around the world.
      Cerebral ischemia to the posterior fossa is more critical and difficult to treat.
      This is primarily due to complex anatomy and physiology of the posterior fossa
      cerebal circulation. There has been multiple modalities tested over the years to
      treat posterior fossa ischemia which have definitely contributed in the outcome
      in patients with this complex problem. Improving the blood flow in the areas of
      brain at risk in properly selected patients could prevent impending cerebral
      ischemia and infarction. Today, there are mainly three types of treatment offered
      to patients with posterior cerebral ischemia. These are (a) medical, (b)
      endovascular and (c) surgical. The recent advances in technology, the diagnosis
      and mode of therapy, has definitely improved the outcomes of cerebral ischemia.
      We discuss the multidisciplinary treatment of posterior circulation ischemia.
      Various pre-operative and operative techniques involved in treating patients with
      posterior cerebral ischemia are discussed.

PMID- 14977061
TI  - Sella turcica metastasis from follicular carcinoma of thyroid.
AB  - A case of metastasis to the sella turcica from a follicular adenocarcinoma of the
      thyroid gland is presented. Metastasis to this site is rare and review of the
      literature reveals only 12 cases of metastatic thyroid carcinoma involving the
      sella turcica and pituitary gland. The optimal treatment strategy is still to be
      determined. A 43-year-old woman presented with headache, nausea, visual
      impairment and galactorrhea. An MRI scan of the cranium revealed an enhancing
      destructive sellar lesion. The patient underwent transsphenoidal removal of the
      lesion to alleviate visual loss. The histological features of the sellar tumor
      were identical to those of a follicular adenocarcinoma partially removed from the
      thyroid gland 22 months earlier. Total thyroidectomy followed by three courses of
      iodine-131 ablation enhanced with synthetic thyrotropin and thyroid hormone
      suppression therapy was instituted. The post-operative course was satisfactory
      with improved vision and ceased galactorrhea. This case was successfully treated
      with a combination of surgical removal, iodine-131 ablation and hormone
      suppression therapy, which resulted in disease control duration of four years.
      Sella turcica metastases of thyroid carcinoma are exceedingly rare and currently
      there are no established therapeutic guidelines.

PMID- 14977062
TI  - Simultaneous ischemic and neurotoxic brain damage after coronary angiography.
AB  - Transient cortical blindness following intra-arterial catheter angiography is a
      known rare complication. We report the case of a 56-year-old man who suffered
      from transient cortical blindness and neuropsychological deficits after coronary
      angiography. Serial CT scans revealed reversible pathologic parenchymal contrast
      enhancement of the right occipital lobe as well as left middle cerebral artery
      infarction at the same time. CT changes and time course of clinical symptoms are
      presented and discussed for both lesions of presumably different etiology.

PMID- 14977063
TI  - Dystrophin deletions and cognitive impairment in Duchenne/Becker muscular
      dystrophy.
AB  - Analyses of deletions in the dystrophin gene and of cognitive status were
      performed on patients with Duchenne (DMD) or Becker (BMD) muscular dystrophy in
      order to find a correlation between both features. Molecular study by multiplex
      and simplex PCR of dystrophin exons led to the identification of 51 deletions in
      126 unrelated patients. Most of them were frameshift, in full agreement with
      severe clinical symptoms, three patients with a BMD-like phenotype had in-frame
      mutations. Deletions were localized with reference to the different dystrophin
      isoform sequences and were clustered in two main areas, 5' and central+ 3' end of
      the gene. Cognitive abilities were tested in 47 out of 51 patients with
      identified mutations, 23 of them being mentally impaired. Comparison of molecular
      and neuropsychological features showed that deletions localized in central and 3'
      parts of the gene (18 out of 23) are preferentially associated with mental
      impairment. Fourteen of them were found in the regulatory and coding sequences
      for the three CNS specific carboxy terminal isoforms. Therefore, though mutations
      with variable locations may lead to cognitive impairment, our results show that
      deletions in the distal portion of the gene are basically related to mental
      retardation.

PMID- 14977064
TI  - Loss of heterozygosity on chromosomes 10q, 9p, 17p and 13q in malays with
      malignant glioma.
AB  - Recent advances in neuro-oncology have revealed different pathways of molecular
      oncogenesis in malignant gliomas including loss of heterozygosity on chromosomal
      regions harboring tumor suppressor genes. In the present study, we performed
      polymerase chain reaction-loss of heterozygosity (PCR-LOH) analysis using
      microsatellite markers to identify loss of heterozygosity on chromosomes 10q, 9p,
      17p and 13q in the Malays with malignant gliomas. Of 12 cases with allelic
      losses, seven (58.3%) cases showed LOH on chromosome 10q, three (25.0%) cases
      showed LOH on chromosome 9p, four (33.3%) cases showed LOH on chromosome 17p and
      two (16.7%) cases showed LOH on chromosome 13q. The cases include five (41.7%)
      cases of glioblastoma multiforme, three (25.0%) cases of anaplastic astrocytoma,
      three (25.0%) cases of anaplastic oligodendroglioma and one (8.3%) case of
      anaplastic ependymoma. Four cases showed loss of heterozygosity on more than one
      locus. Our findings showed that loss of heterozygosity on specific chromosomal
      regions contributes to the molecular pathway of glioma progression in Malay
      population. In addition, these data provide useful evidence of molecular genetic
      alterations of malignant glioma in South East Asian patients, particularly in the
      East Coast of Malaysia.

PMID- 14977065
TI  - Single slice method for quantification of hemorrhagic transformation using direct
      ELISA.
AB  - An important area of experimental stroke research addresses the development of
      brain hemorrhage after cerebral ischemia. Investigations of hemorrhagic
      transformation, however, have been compromised by the absence of sensitive
      methods for quantification of hemorrhagic transformation. We have developed a
      direct ELISA method that is sensitive, reproducible and can be conducted on
      tissue treated with triphenyltetrazolium chloride, a stain commonly used for
      infarct size determination. We have also localized the slices containing the most
      hemoglobin to facilitate a single slice analysis. This allows two essential
      variables in experimental stroke research to be assessed on the same slice,
      leaving the rest of the brain available for other analysis.

PMID- 14977066
TI  - Doppler microembolic signals during cardiopulmonary bypass: comparison of two
      membrane oxygenators.
AB  - We undertook this study to evaluate the dependence of Doppler microembolic signal
      (MES) counts, detected during cardiopulmonary bypass, on the type of oxygenator
      used. A total of 90 patients, 71 men and 19 women, aged 60 +/- 10 years (mean +/-
      SD), undergoing elective cardiac surgery for coronary artery bypass grafting (one
      vessel, n = 6; two vessels, n = 24; three vessels, n = 33; four vessels, n = 9)
      or valve replacement (mitral valve, n = 2, aortic valve, n = 15, both valves, n =
      1) were monitored with transcranial Doppler sonography during the complete
      surgical procedure. The surgical and anesthetic techniques were standardized in
      all patients, except for the type of membrane oxygenator used (COBE CML Duo, n =
      55 or DIDECO D 703, n = 35). MES count was expressed as total number of MES
      detected in both middle cerebral arteries during cardiopulmonary bypass (CPB) and
      also as total MES number divided by the CPB duration in minutes (MES min(-1)). No
      significant differences in patients' age or sex and type and duration of
      operation were noted between the two groups. MES incidence while the patients
      were on cardiopulmonary bypass was 100%. MES counts during CPB were 309 (236-502)
      and 143 (86-233) for DIDECO and COBE oxygenators, respectively (p < 0.00001). MES
      min(-1) were also significantly higher in patients operated with DIDECO, as
      compared to COBE oxygenators (3.7 (2.4-5.6) versus 1.5 (1-2.4), respectively, p <
      0.0001). Inter-observer variability was satisfactory (k = 0.72). Use of a DIDECO
      D 703 oxygenator resulted in significantly higher MES counts as compared to the
      COBE CML Duo oxygenator. The clinical relevance of this finding remains to be
      determined.

PMID- 14977067
TI  - Neuroprotective effect of combination of poly (ADP-ribose) polymerase inhibitor
      and antioxidant in middle cerebral artery occlusion induced focal ischemia in
      rats.
AB  - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical
      Education and Research, Punjab, India We have investigated the neuroprotective
      potential of combination of poly (ADP-ribose) polymerase inhibitor (nicotinamide
      or 3-aminobenzamide) and antioxidant (melatonin) in middle cerebral artery
      occlusion (MCAo) induced focal ischemia in rats. MCAo of 2 h followed by 22 h
      reperfusion produced large volume of cerebral infarction (mean +/- SEM 211.38 +/-
      8.35 mm3), volume of edema (60 +/- 2 mm3) and neurological deficits (4.45 +/-
      0.25). Combination of nicotinamide (500 mg kg(-1), i.p.) and melatonin (10 mg kg(
      1), i.p.) significantly decreased infarct volume to 48 +/- 2.58 mm3 as compared
      to their individual drug (nicotinamide 76 +/- 12.49mm3, melatonin 76.17 +/- 1.24
      mm3). A significant improvement was observed in edema volume and neurological
      deficits with this combination. Combination of 3-aminobenzamide (20 mg kg(-1),
      i.p.) and melatonin (10 mg kg(-1), i.p.) also produced similar reduction in
      infarction, edema and neurological score. These results indicate that the
      combination of poly (ADP-ribose) polymerase inhibitor and antioxidant produce
      enhanced neuroprotection. Clinical availability and wide therapeutic margin of
      nicotinamide and melatonin make them a promising drug combination for clinical
      evaluation in stroke patients.

PMID- 14977068
TI  - Acute ethanol intoxication in a model of traumatic brain injury: the protective
      role of moderate doses demonstrated by immunoreactivity of synaptophysin in
      hippocampal neurons.
AB  - Although ethanol intoxication is reported to be a complicating factor in
      traumatic brain injury, some recent studies are indicating its possible
      protective role especially at lower doses. Ethanol inhibition of NMDA-mediated
      excitotoxicity which predominates at lower doses is believed to be responsible
      for this protection. The aim of this study was to demonstrate this
      neuroprotective role of alcohol using immunoreactivity for synaptophysin as an
      indirect marker for severity of injury. Acute ethanol intoxication at moderate
      doses was performed 2 h prior to trauma. Severe traumatic brain injury was
      administrated using an impact acceleration model in Sprague-Dawley rats. At post
      traumatic 48th hour, immunorectivity for synapthophysin in the rat hippocampi was
      evaluated under light microscopy. According to our results there were slight
      increases in immunoreactivity for synaptophysin in the stratum oriens and
      striatum radiatum of CA1 subfield of hippocampus when ethanol was administered
      prior to trauma comparing to moderate increase in the trauma-only group. On the
      other hand vacuolar degeneration and red neuron formation was more prominent in
      the pyramidal cell layer of CA1 and CA3 when ethanol was not administered.
      Ethanol may have a neuroprotective role when administered at moderate doses prior
      to traumatic brain injury. This effect of ethanol may primarily be due to
      inhibition of NMDA receptors.

PMID- 14977069
TI  - Primary extracranial meningioma in the vicinity of the temporal bone: a benign
      lesion which is rarely recognized clinically.

PMID- 14977070
TI  - Bone marrow cells as an origin of immune-mediated hearing loss.
AB  - The MRL/lpr mouse, which is homozygous for the recessive lpr genes and has a
      mutation in the Fas gene encoding a cell-surface receptor for apoptosis, exhibits
      severe lymphadenopathy and develops systemic lupus erythematosus (SLE)-like
      disease. It has recently been reported that this mouse also manifests
      sensorineural hearing loss (SHL) with cochlear pathology at 20 weeks of age. We
      examined the effects of reconstituting severe combined immunodeficient (SCID)
      mice with MRL/lpr bone marrow on the development of SHL. These mice normally
      develop neither SHL nor cochlear pathology. Immune-mediated SHL and cochlear
      pathology did, indeed, occur following transfer of MRL/lpr bone marrow into SCID
      mice. These findings suggest that the development of SHL and cochlear pathology
      observed in MRL/lpr mice and in SCID mice receiving MRL/lpr bone marrow are the
      result of bone marrow defects rather than the result of a problem intrinsic to
      the cochlea.

PMID- 14977071
TI  - Additive effects of toxin exposure and destruction of semicircular canal on
      cochlear function: an auditory brainstem response study in the rat.
AB  - OBJECTIVE: To ascertain whether the severity of toxin-related hearing loss and
      the interval between instillation of toxin and surgical trauma affect hearing
      recovery capacity following semicircular canal (SCC) surgery in the rat. MATERIAL
      AND METHODS: Twelve rats were injected with Pseudomonas aeruginosa exotoxin A
      (PaExoA). Auditory brainstem responses (ABRs) were measured 72 h and 3 weeks
      later. Depending on the severity of hearing loss, the rats were divided into two
      groups: those with moderate (Group A; n = 6) and severe (Group B; n = 6) hearing
      loss. Three rats from Group A were then operated on 3 weeks after toxin exposure
      and the other three 3 months after instillation of toxin. All Group B rats were
      operated on after 3 months. RESULTS: In Group A, post-surgical hearing loss
      recovered to a varying degree but rats in Group B showed little or no hearing
      recovery capacity. This difference was statistically significant. When the six
      rats with moderately toxin-affected ears were compared, statistical differences
      in recovery capacity between those operated on at 3 weeks and at 3 months were
      also detected. The group with a shorter interval showed significantly less
      hearing recovery of inner ear function following surgical trauma. CONCLUSION:
      When the toxin causes severe hearing damage there is no capacity for cochlear
      recovery following additional surgical trauma. When the rat inner ear is
      moderately affected by PaExoA, the interval between toxin exposure and SCC
      destruction plays a significant role in the ultimate hearing outcome. Cochlear
      recovery potential seems to be weakened in close temporal proximity to toxin
      exposure, but recovers with the passage of time.

PMID- 14977072
TI  - Histology of the utricle in kinetotically swimming fish: a parabolic aircraft
      flight study.
AB  - OBJECTIVES: Humans taking part in parabolic aircraft flights (PAFs) may suffer
      from space motion sickness, which is a form of kinetosis. As it has been
      repeatedly shown that some fish in a given batch also reveal kinetotic behaviour
      (especially so-called spinning movements and looping responses) during PAFs, and
      as a result of the homology of the vestibular apparatus of all vertebrates, fish
      can be used as model systems to investigate the origin of susceptibility to
      motion sickness. Therefore. we were prompted to examine the utricular maculae,
      which are responsible for the internalization of gravity in teleosteans of fish
      swimming kinetotically in microgravity (microg) in comparison with those of
      animals from the same batch who swam normally. MATERIAL AND METHODS: Larval
      cichlid fish (Oreochromis mossambicus) were subjected to PAFs. Post-flight,
      animals which had behaved normally or kinetotically during the microg phases were
      examined histologically The sizes of the inner ear utricular maculae as well as
      the numbers of sensory and supporting cells were determined. RESULTS: The total
      numbers of both sensory and supporting cells of the utricular maculae did not
      differ between kinetotic and normally swimming fish. Cell density (number of
      sensory and supporting cells/100 microm2) was, however, reduced in kinetotic
      animals (p < 0.0001), which seemed to be due to the presence of malformed
      epithelial cells of increased size in the kinetotic specimens. CONCLUSION: These
      results indicate that susceptibility to kinetosis may originate from genetically
      predisposed malformed sensory epithelia.

PMID- 14977073
TI  - Bacteriology of mastoid subperiosteal abscess in children.
AB  - OBJECTIVE: Subperiosteal abscess (SA) is the most frequent complication of acute
      mastoiditis (AM). Of pathogens cultured from the external auditory canal or
      middle ear during myringotomy, 15% may be different from microorganisms isolated
      from the SA. We suggest, therefore, that only cultures obtained from the abscess
      cavity can truly reflect the bacteriology of this complication of AM. The purpose
      of our study was to analyze the infectious agents which cause SA and mastoid
      cortex erosion in children. MATERIAL AND METHODS: The medical records of 35
      children who underwent mastoidectomy for SA between May 1984 and April 2002 were
      evaluated. RESULTS: Mastoid cortex erosion was found at surgery in 72.7% of
      abscesses Purulent discharge was obtained from the SA cavity in 28 cases. The
      commonest pathogens isolated in these cases, as well as in 18 cases of mastoid
      cortex erosion, were Staphylococcus aureus and Streptococcus pyogenes, followed
      by Streptococcus pneumoniae. Hemophilus influenzae, Pseudomonas aeruginosa,
      Escherichia coli and Klebsiella pneumoniae. Sterile culture was found in 25% of
      cases. CONCLUSIONS: Mastoid SA is a unilateral disease that can recur. Early
      administration of anti-Staphylococcus medications should be considered for
      patients with SA as a complication of AM.

PMID- 14977074
TI  - Movements of the intact and reconstructed ossicular chain during changes in
      static pressure.
AB  - OBJECTIVE: To investigate the motion of the normal and reconstructed ossicular
      chain during changes in static pressure. MATERIAL AND METHODS: Experiments were
      carried out using seven fresh human temporal bones Using digital photography,
      movements of the malleus were measured during incremental pressure changes
      between +500 and -500 daPa with the incus in situ and following its removal. The
      pattern of movement of the ossicles was recorded in the form of digital video
      clips. This was carried out with the ossicular chain intact and also when it had
      been reconstructed with an incus graft and four different types of artificial
      prosthesis. RESULTS: The lateral to medial movement of the malleus during changes
      in static pressure is converted into a predominantly superior to inferior
      movement of the incus. Conventional reconstructions using a graft or prosthesis
      transmit the malleus movement directly to the stapes so that it is pushed in and
      out of the oval window. Reconstructions with prostheses which restore the
      mammalian three-ossicle pattern, by contrast, move in a similar manner to the
      normal incus. CONCLUSION: Ears reconstructed using conventional techniques are
      more at risk from pressure changes than those in which a "physiological" method
      is used.

PMID- 14977075
TI  - All-trans retinoic acid induces mucociliary differentiation in a human
      cholesteatoma epithelial cell culture.
AB  - OBJECTIVES: Retinoic acid (RA) can prevent keratin formation and induce mucous
      differentiation in epithelia. In this study, we attempted to induce keratinizing
      squamous epithelium from human cholesteatoma epithelial (HCE) cells using an air
      liquid interface (ALI) technique. We also examined the effect of RA on the
      phenotype of keratinizing HCE cells. MATERIAL AND METHODS: HCE cells were
      cultured in RA-free defined media at an ALI or in a submerged state. We examined
      the morphological differences between ALI and submerged cultures, and
      histologically investigated the changes of phenotype after RA treatment. We also
      determined the effect of RA on the mRNA expressions of the cornifin-alpha and
      mucin genes as indicators of squamous and mucous differentiation, respectively.
      RESULTS: Using an ALI technique, we were able to differentiate HCE cells into a
      keratinizing squamous epithelium. When we treated the keratinizing HCE cells with
      RA, the morphological phenotype progressively changed into mucociliary
      epithelium. In addition, the expression of cornifin-alpha mRNA was suppressed,
      and the expressions of mucin gene 5AC (MUC5AC) and MUC5B mRNA increased
      progressively with RA treatment. CONCLUSION: We successfully developed a
      culturing system for keratinizing differentiation of HCE cells using the ALI
      technique in a defined medium. Our study also clearly showed that RA treatment
      led to mucociliary differentiation of HCE cells.

PMID- 14977076
TI  - Horizontal vestibulo-ocular reflex dynamics in acute vestibular neuritis and
      viral labyrinthitis: evidence of otolith-canal interaction.
AB  - OBJECTIVE: To evaluate the dynamic properties of the horizontal vestibulo-ocular
      reflex (h-VOR) in the acute stage of two common labyrinthine diseases that
      provoke severe attacks of vertigo with spontaneous nystagmus: vestibular neuritis
      (vestibular loss alone) and viral labyrinthitis (cochleovestibular loss).
      MATERIAL AND METHODS: Sixty-three patients were investigated: 42 were diagnosed
      with vestibular neuritis and 21 with viral labyrinthitis. The h-VOR function was
      evaluated by conventional caloric and impulsive testing. A simplified model of
      vestibular function was used to analyze the vestibulo-ocular response to
      rotational stimulation. RESULTS: The results showed a significant difference in h
      VOR characteristics between the two pathologies. Patients with vestibular
      neuritis exhibited a strong horizontal semicircular canal deficit, but no h-VOR
      asymmetry between the two rotational directions. In contrast, patients with viral
      labyrinthitis demonstrated moderate canal paresis and a marked h-VOR deficit in
      rotation toward the affected ear. CONCLUSION: These findings support the
      hypothesis that the h-VOR dynamic asymmetry that occurs after an acute unilateral
      inner ear lesion is not due to canal dysfunction alone, but involves complex
      adaptive changes in the central VOR that may implicate the otolith system. Based
      on histopathologic and clinical differences in the two pathologies reported in
      the literature, we postulate that this otolith-canal interaction is mainly linked
      to the loss of saccular function.

PMID- 14977077
TI  - Function of semicircular canals, utricles and saccules in deaf children.
AB  - OBJECTIVE: To study vestibular function in deaf children. MATERIAL AND METHODS:
      In 36 deaf children the function of the semicircular canals, saccules and
      utricles was measured by means of caloric testing, recordings of vestibular
      evoked myogenic potentials (VEMPs) and measurements of the subjective visual
      horizontal (SVH) at different body tilts, respectively. RESULTS: In total, 30% of
      subjects had caloric hypo- or areflexia and 24% had a caloric asymmetry. VEMPs
      were weak or absent bilaterally in 22% of cases, and asymmetric in 19%. Regarding
      the utricle, 17% of subjects had a pathologically reduced perception of roll tilt
      to both sides and 25% had an asymmetry. In total, 30% of subjects were pathologic
      in all 3 tests and 30% were completely normal. Semicircular canal function
      correlated best with the function of the saccule. If hearing was better than 90
      dB (pure-tone average of 0.5, 1.0 and 2.0 kHz) vestibular function was often
      normal. For hearing levels of 100-120 dB, otolith function declined
      significantly. CONCLUSIONS: Vestibular function tends to be preserved up to a
      point where hearing is nearly extinct. Hearing level correlates more closely with
      otolith function, especially that of the utricle, than with semicircular canal
      function.

PMID- 14977078
TI  - Clinical and epidemiological study of vertigo at an outpatient clinic.
AB  - OBJECTIVES: The main goal of this study was to set up a database of vertigo
      patients that could serve as a reference for other ENT services treating these
      pathologies. We present a clinical and epidemiological study of vertigo in an ENT
      outpatient clinic in 2001 and describe our diagnosis protocol. MATERIAL AND
      METHODS: This was a prospective study of 591 patients (18% of the total number of
      3283 first visits) controlled and treated at the ENT service of the Hospital
      Clinic in Barcelona. The main variables studied were sex, age, clinical
      characteristics and the results of physical and basic instrumental examinations.
      RESULTS: After obtaining a clinical history and performing a physical
      examination, pure-tone audiometry, impedance audiometry and
      electronystagmography, 394 patients were discharged with a medical report,
      diagnosis and prescription for treatment. The other 197 patients whom the
      standard examination was unable to diagnose were referred to a multidisciplinary
      committee for re-evaluation. CONCLUSION: A correct diagnosis is essential to
      ensure adequate treatment and attain an acceptable balance between cost and
      effectiveness.

PMID- 14977079
TI  - Intraoperative auditory monitoring in vestibular schwannoma surgery: new trends.
AB  - OBJECTIVE: To investigate the efficiency of a new method of brainstem auditory
      evoked potential (BAEP) monitoring during complete vestibular schwannoma (VS)
      resection with attempted hearing preservation. MATERIAL AND METHODS: Dedicated
      software providing near real-time recording was developed using a rejection
      strategy of artifacts based on spectral analysis. A small sample number (maximum
      200) is required and results are obtained within 10 s. Fourteen consecutive
      patients with hearing class A operated on for VS, in an attempt to preserve
      hearing, participated in the investigation. Postoperatively, 7 patients (50%) had
      useful hearing (hearing class A, 4/14; hearing class B, 3/14) on the operated
      side. Seven patients (50%) were reduced to hearing class D. RESULTS: Drilling of
      the internal auditory canal (IAC) and tumor removal at the lateral end of the IAC
      were identified as the two most critical steps for achieving hearing
      preservation. Intraoperative BAEP monitoring was sensitive in detecting auditory
      damage with useful feedback but its effectiveness in preventing irreversible
      hearing impairment was not demonstrated in this study. CONCLUSION: Combined BAEP
      and direct auditory nerve monitoring using the same equipment will be performed
      in the future in an attempt to enhance the chances of preventing irreversible
      hearing damage, and possibly to improve the hearing outcome significantly.

PMID- 14977080
TI  - Establishing normal hearing with the dichotic multiple-frequency auditory steady
      state response compared to an auditory brainstem response protocol.
AB  - OBJECTIVE: To determine the clinical usefulness of the dichotic multiple
      frequency (MF) auditory steady-state response (ASSR) technique for estimating
      normal hearing compared to a 0.5-kHz tone burst and broadband click auditory
      brainstem response (ABR) protocol in a sample of adults. MATERIAL AND METHODS: A
      comparative experimental research design was selected in order to compare
      estimations of normal hearing obtained with the dichotic ASSR technique at 0.5,
      1, 2 and 4 kHz with a 0.5-kHz tone burst and broadband click ABR protocol. The
      recording times required for each procedure were also compared. Normal-hearing
      subjects (n = 28) were selected according to immittance values within normal
      limits and pure-tone behavioural thresholds of < 25 dB HL across frequencies.
      RESULTS: The dichotic MF ASSR estimated normal hearing to be, on average, 30-34
      dB HL across the range 0.5-4 kHz. The mean estimate of normal hearing for 0.5 kHz
      using tone burst ABRs was 30 dB nHL and the mean click ABR threshold was 16 dB
      nHL, i.e. 14-18 dB better than the ASSR thresholds. The dichotic MFASSR technique
      recorded 8 thresholds (4 in each ear) in a mean time of 23 min. The ABR protocol
      recorded 4 thresholds (2 in each ear) in a mean time of 25 min. CONCLUSION: Both
      the dichotic MF ASSR and ABR protocols provided a time-efficient estimation of
      normal hearing. There was no significant difference between the tone burst ABR
      and MF ASSR techniques in terms of estimation of normal hearing at 0.5 kHz. The
      dichotic MF ASSR technique proved more time-efficient by determining more
      thresholds in a shorter time compared to the ABR protocol.

PMID- 14977081
TI  - The aging ear: an otomicroscopic and tympanometric study.
AB  - OBJECTIVES: To analyze changes in tympanometric measures with age and to study
      some otitis-related issues in the elderly (> or = 60 years) population. MATERIAL
      AND METHODS: The study was designed as a combination of a cross-sectional survey
      and a controlled study. We studied a random sample of 232 elderly subjects using
      an extended battery of audiological tests, including pure-tone audiometry.
      tympanometry with a probe frequency of 226 Hz, otomicroscopy and a standardized
      questionnaire. A sample of 60 otologically normal subjects were selected for
      comparative analysis with young healthy controls, and for description of age
      related changes and gender differences. RESULTS: Using linear regression analyses
      of ear canal volume, middle ear pressure and tympanic membrane compliance on age,
      no consistently significant change in these parameters with age was found. When
      these measures were compared between the elderly and the controls, using
      parametric and non-parametric statistical tests, no significant differences were
      found for either gender. The only significant gender difference was found for ear
      canal volume, which was greater for elderly males than for elderly females In the
      unscreened elderly sample, the adjusted prevalence for reported previous or
      current otitis media was 15-27% of the population (95% CI). The adjusted
      prevalence for reported previous or current chronic otitis media (COM) or
      sequelae thereof was 1-7% (95% CI). With the exception of cerumen obstruction,
      the prevalence of outer ear canal-related complaints was 1-7% (95% CI). There
      were some discrepancies between these reported complaints and the findings at
      otomicroscopy. Although elderly subjects with COM were found to have poorer
      hearing at speech frequencies than normal elderly subjects. no such effect was
      found in subjects with scarring or atrophy of the tympanic membrane. The effect
      of pathological findings at otomicroscopy on tympanometric measures in the
      elderly sample was highly variable and no consistent association was found.
      CONCLUSIONS: No change in middle ear sound transmission, as assessed by
      tympanometry, occurs with normal aging. Ear canal volume is smaller in elderly
      females than elderly males, which is potentially relevant to the study of
      otoacoustic emissions in the elderly. The estimated prevalence of ear canal
      related problems, excluding cerumen obstruction, is of such a magnitude that the
      introduction of partially implanted hearing aids may be warranted in our elderly
      population.

PMID- 14977082
TI  - Clinical relevance of nasal polyps in individuals recruited from a general
      population-based study.
AB  - OBJECTIVE: To compare the clinical presentations of individuals with nasal polyps
      detected by endoscopy in a general population sample with those of patients with
      nasal polyp disease seeking medical attention. MATERIAL AND METHODS: A total of
      38 individuals with nasal polyps from a population-based sample were compared
      with 38 matched controls and a third group consisting of 44 patients who
      presented to an outpatient clinic with symptoms and diagnosed nasal polyps Upper
      and lower airway symptoms were registered. Polyp size, peak nasal inspiratory
      flow (PNIF), olfactory function and health-related quality of life were measured.
      RESULTS: Compared with the individuals with nasal polyps in the population
      sample, patients actively seeking medical care for nasal polyposis experienced
      more symptoms of nasal blockage and an impaired sense of smell, and had more
      extensive polyps and reduced PNIF. There were equal frequencies of asthma
      symptoms in these two groups. Compared with the controls, the individuals with
      nasal polyps in the population sample had a greater frequency of asthma symptoms
      and aspirin intolerance and also experienced an impaired sense of smell.
      CONCLUSION: Nasal polyps alone, as seen occasionally, are indicative of airway
      disease involving the upper and lower respiratory tracts.

PMID- 14977083
TI  - Value of digital high-speed endoscopy in addition to videofluoroscopic imaging of
      the neoglottis in tracheoesophageal speech.
AB  - OBJECTIVE: To gain insight into the clinical value of using the relatively new
      evaluation tool digital high-speed endoscopy in addition to the widely used
      method of videofluoroscopy for imaging of the neoglottis in tracheoesophageal
      speech after total laryngectomy. MATERIAL AND METHODS: Anatomical and morphologic
      characteristics of the neoglottis in 37 laryngectomized patients using
      tracheoesophageal speech were studied by means of visual assessment of digital
      high-speed endoscopy recordings and visual assessment and quantitative measures
      of videofluoroscopy recordings, using previously published protocols. RESULTS:
      Digital high-speed endoscopy provides information complementary to that of
      videofluoroscopy with respect to the location of the vibration, presence of a
      mucosal wave, regularity of the vibration and closure of the neoglottis The
      information provided by digital high-speed endoscopy overlaps with that provided
      by videofluoroscopy with respect to the amount of saliva (regurgitation of barium
      in videofluoroscopy) and the visibility of the origin of the neoglottis (presence
      of a neoglottic bar in videofluoroscopy). Additionally, relationships were found
      between the visual assessments of the high-speed recordings and some patient
      characteristics. CONCLUSIONS: Digital high-speed endoscopy provides additional
      insight into neoglottic characteristics that cannot be studied with
      videofluoroscopy. The application of both imaging methods enhances the insight
      into tracheoesophageal voicing.

PMID- 14977084
TI  - Molecular analysis of p21 promoter activity isolated from squamous carcinoma cell
      lines of the head and neck under the influence of 1,25(OH)2 vitamin D3 and its
      analogs.
AB  - OBJECTIVE: The biologically active 1,25(OH)2 vitamin D3 and its analogs have been
      shown to have antiproliferative and differentiating effects in a variety of
      malignant and non-malignant cells. For squamous carcinoma cell lines of the head
      and neck (SCCHN) we could show that this antiproliferative activity of 1,25(OH)2
      vitamin D3 is due to induced expression of the cell-cycle inhibitory proteins p21
      and p27, causing an arrest in the G0/G1 cell-cycle phase. MATERIAL AND METHODS:
      In this work we investigated the effects of three vitamin D3 analogs, EB1089,
      MC1288 and CB1093, on proliferation behavior and cell-cycle status in a laryngeal
      carcinoma cell line (JPPA) as well as in control human immortalized keratinocytes
      (HaCaT). To study the molecular mechanism the functional activity of the promoter
      region of p21, a potential target gene of vitamin D3 transcriptional regulation,
      was investigated. For this reason a 2.7-kb fragment of the p21 promoter was
      isolated by polymerase chain reaction from HaCaT, JPPA and SCC9 (tongue
      carcinoma) cells and directionally cloned into an enhanced green fluorescence
      protein (EGFP) reporter gene vector system. A construct was used to stably
      transfect HaCaT cells and to monitor the expression of the EGFP gene by confocal
      microscopy. RESULTS: Analysis of proliferation and cell-cycle status revealed
      decreased growth rates and G0/G1I cell-cycle arrest in cells treated with
      1,25(OH)2 vitamin D3 and its analogs The EGFP reporter gene-transfected cells
      showed distinct fluorescence under the influence of 1,25(OH)2 vitamin D3 and its
      analogs compared to control cells. CONCLUSION: These results demonstrate that the
      cell-cycle inhibitor protein p21 is a direct target gene of biologically active
      1,25(OH)2 vitamin D3, inducing G0/G1 cell-cycle arrest. The ability of vitamin D
      analogs to act via the same molecular mechanism as the natural hormone but with
      less hypercalcemic activity may have therapeutic implications for patients with
      SCCHN malignancy.

PMID- 14977085
TI  - Upper aerodigestive tract squamous cell carcinoma: distribution of extracapsular
      spread and soft tissue deposits in the neck.
AB  - OBJECTIVE: Extracapsular spread (ECS) and soft tissue deposits (STD) of squamous
      cell carcinoma (SCC) in the neck of patients with metastatic SCC of the upper
      aerodigestive tract have been shown to adversely affect actuarial and disease
      free survival. No studies to date have detailed the distribution of ECS and STD
      within the neck. MATERIAL AND METHODS: A total of 215 neck dissections from 155
      patients were prospectively collected and analysed for the presence of both STD
      and ECS. As no classification for STD exists, their distribution was classified
      according to the nodal levels used for classification of cervical lymph nodes as
      described by the Memorial Sloan-Kettering Cancer Center. RESULTS: A total of 81
      neck dissections from 59 patients were found to have either metastatic lymph
      nodes with ECS, STD or both. The distribution of lymph node metastasis, ECS and
      STD was very similar. Level II was most frequently affected, with Levels III and
      IV being affected less frequently. There were very few lymph node metastases to
      Level V, and this level contained no evidence of either ECS or STD. CONCLUSION:
      The method of pathological assessment of neck dissection specimens and reporting
      on the presence of ECS and STD has not been formalized. By analysing neck
      dissection specimens in the manner described we can report on the presence or
      absence of ECS and STD with increased accuracy. This has considerable
      implications for patient management.

PMID- 14977086
TI  - Epidermal growth factor receptor and p53 expression in T1-T2 glottic cancer
      involving the anterior or posterior commissure.
AB  - OBJECTIVE: We surveyed retrospectively the expression of epidermal growth factor
      receptor (EGFR) and p53 in cases of T1-T2 glottis cancer involving the anterior
      (AC) or posterior commissure (PC) subsites to check for differences possibly
      explaining the different prognoses of cancer at these subsites. MATERIAL AND
      METHODS: Between 1970 and 1995, 15 patients with T1-T2 primary glottis cancer
      involving the PC, either partly or entirely, were treated. Thirty more cases were
      selected among 184 patients treated during the same time period for AC glottis
      cancer, to match the former cases with regard to age, sex, tumor stage, smoking
      habits and alcohol consumption. RESULTS: A significantly higher frequency of EGFR
      expression occurred in PC than in AC cancer. CONCLUSION: These results, and the
      anatomy of the PC subsite, may explain the more frequent recurrence of T1-T2 PC
      compared to T1-T2 AC cancer and why radiotherapy achieves worse results in T1-T2
      PC cancer than in AC cancer of comparable T grade.

PMID- 14977087
TI  - Head and neck metastases from occult abdominal primary site: a case report and
      literature review.
AB  - OBJECTIVES: A very rare case of cervical lymph node metastasis from the liver is
      reported. The clinical findings and the diagnosis of a metastasis to the head and
      neck from the isolated silent abdominal cancer are discussed. MATERIAL AND
      METHODS: The clinical and histopathological findings of a 56-year-old woman with
      a metastatic cervical lymph node of unknown origin are presented, together with a
      literature review of metastases from an occult abdominal primary. RESULTS: The
      primary site was identified as an undifferentiated cholangiolocellular carcinoma
      using immunostaining for anti-cytokeratin subclasses after autopsy. Fifty-two
      cases of head and neck metastases from an abdominal primary cancer were found and
      separately summarized according to the metastatic routes. CONCLUSIONS: When a
      metastatic neck cancer of unknown origin is diagnosed, it is very important to
      consider the possibility of a metastasis from an abdominal organ. Recognition of
      metastatic routes and their characteristics is helpful in the search for the
      occult abdominal primary site. Immunohistochemistry of the metastatic cancer may
      provide important information for identifying the primary site in cases of
      metastasis of an undifferentiated carcinoma.

PMID- 14977088
TI  - Cost and efficiency within health care systems.

PMID- 14977089
TI  - Performance of US teaching hospitals: a panel analysis of cost inefficiency.
AB  - This research summarizes an analysis of the impact of environment pressures on
      hospital inefficiency during the period 1990-1999. The panel design included 616
      hospitals. Of these, 211 were academic medical centers and 415 were hospitals
      with smaller teaching programs. The primary sources of data were the American
      Hospital Association's Annual Survey of Hospitals and Medicare Cost Reports.
      Hospital inefficiency was estimated by a regression technique called stochastic
      frontier analysis. This technique estimates a "best practice cost frontier" for
      each hospital that is based on the hospital's outputs and input prices. The cost
      efficiency of each hospital was defined as the ratio of the stochastic frontier
      total costs to observed total costs. Average inefficiency declined from 14.35% in
      1990 to 11.42% in 1998. It increased to 11.78% in 1999. Decreases in inefficiency
      were associated with the HMO penetration rate and time. Increases in inefficiency
      were associated with for-profit ownership status and Medicare share of
      admissions. The implementation of the provisions of the Balanced Budget Act of
      1997 was followed by a small decrease in average hospital inefficiency. Analysis
      found that the SFA results were moderately sensitive to the specification of the
      teaching output variable. Thus, although the SFA technique can be useful for
      detecting differences in inefficiency between groups of hospitals (i.e., those
      with high versus those with low Medicare shares or for-profit versus not-for
      profit hospitals), its relatively low precision indicates it should not be used
      for exact estimates of the magnitude of differences associated with inefficiency
      effects variables.

PMID- 14977090
TI  - Inpatient-outpatient cost shifting in Washington hospitals.
AB  - This paper empirically investigates the phenomenon known as "cost shifting"
      across inpatient and outpatient hospital services. That is, we examine whether,
      when faced with lower government reimbursement for outpatient services, providers
      raise inpatient prices for non-government patients (and analogously for lower
      inpatient government reimbursement). Using a panel of hospitals from Washington
      State, we find that private, nonprofit hospitals do cost shift across types of
      services. We also find that a firm's cost shifting behavior differs based on the
      type government insurance program (i.e., Medicare versus Medicaid). Government
      owned hospitals do not cost shift with respect to any type of government
      insurance plan.

PMID- 14977091
TI  - Addressing bed costs for the elderly: a new methodology for modelling patient
      outcomes and length of stay.
AB  - The proportion of elderly in the population has dramatically increased and will
      continue to do so for at least the next 50 years. Medical resources throughout
      the world are feeling the added strain of the increasing proportion of elderly in
      the population. The effective care of elderly patients in hospitals may be
      enhanced by accurately modelling the length of stay of the patients in hospital
      and the associated costs involved. This paper examines previously developed
      models for patient length of stay in hospital and describes the recently
      developed conditional phase-type distribution (C-Ph) to model patient duration of
      stay in relation to explanatory patient variables. The Clinics data set was used
      to demonstrate the C-Ph methodology. The resulting model highlighted a strong
      relationship between Barthel grade, patient outcome and length of stay showing
      various groups of patient behaviour. The patients who stay in hospital for a very
      long time are usually those that consume the largest amount of hospital
      resources. These have been identified as the patients whose resulting outcome is
      transfer. Overall, the majority of transfer patients spend a considerably longer
      period of time in hospital compared to patients who die or are discharged home.
      The C-Ph model has the potential for considering costs where different costs are
      attached to the various phases or subgroups of patients and the anticipated cost
      of care estimated in advance. It is hoped that such a method will lead to the
      successful identification of the most cost effective case-mix management of the
      hospital ward.

PMID- 14977092
TI  - The 'NICE' approach to technology assessment: an economics perspective.
AB  - The National Institute for Clinical Excellence has published guidelines for
      economic evaluations for considering whether new health care technologies
      contribute to the efficient use of National Health Service resources. The
      analytical basis of the guidelines is a comparison of the costs and consequences
      of new and existing methods for dealing with particular conditions using the
      incremental cost-effectiveness ratio (ICER). However, this fails to provide an
      explicit and systematic basis for addressing the dual objectives of health
      maximisation and equitable availability of technologies in the context of a fixed
      NHS budget. We show that information on the costs and consequences of a
      particular technology is insufficient to address issues of efficiency of resource
      use. In addition, information is required about the total resources available and
      the alternative uses of those resources. Moreover, because these factors are
      unlikely to be identical for all settings, it is unlikely that the efficiency of
      using resources to support a new technology will be the same for all settings,
      even if the cost and consequences of the technology are the same across settings.
      Instead of improving the health outcomes from NHS resources, we show that using
      NICE guidelines to inform decisions about new technologies may lead to increased
      resources allocated to new technology, increased local variations in the use of
      new technologies and concerns about the sustainability and affordability of
      public funding for new technologies.

PMID- 14977093
TI  - Use of quality adjusted life years and life years gained as benchmarks in
      economic evaluations: a critical appraisal.
AB  - Researchers have grappled with various ways of placing the results of an economic
      evaluation in the appropriate context. One of the most common methods is to
      relate the results of a study to an appropriate benchmark (commonly, dollars
      50,000 per QALY in the US or pounds sterling 30,000 per QALY in the UK). This
      paper examines the foundation for these cut-off points and critiques their use by
      researchers. Although it is difficult to establish an appropriate benchmark this
      paper notes that reference points may be too low based on published data.
      Further, the inconsistent application of benchmarks, and differences in the
      calculation of a value of a statistical life, will lead to an inefficient
      allocation of health care resources.

PMID- 14977094
TI  - Measuring case-mix complexity of tertiary care hospitals using DRGs.
AB  - The objectives of the study were to develop a model that measures and evaluates
      case-mix complexity of tertiary care hospitals, and to examine the
      characteristics of such a model. Physician panels defined three classes of case
      complexity and assigned disease categories represented by Adjacent Diagnosis
      Related Groups (ADRGs) to one of three case complexity classes. Three types of
      scores, indicating proportions of inpatients in each case complexity class
      standardized by the proportions at the national level, were defined to measure
      the case-mix complexity of a hospital. Discharge information for about 10% of
      inpatient episodes at 85 hospitals with bed size larger than 400 and their input
      structure and research and education activity were used to evaluate the case-mix
      complexity model. Results show its power to predict hospitals with the expected
      functions of tertiary care hospitals, i.e. resource intensive care, expensive
      input structure, and high levels of research and education activities.

PMID- 14977096
TI  - The impact of spatial structure on the accuracy of contour maps of small data
      sets.
AB  - Spatial analysis of insect counts provides important information about how insect
      species respond to the heterogeneity of a given sampling space. Contour mapping
      is widely used to visualize spatial pest distribution patterns in anthropogenic
      environments, and in this study we outlined recommendations regarding
      semivariogram analysis of small data sets (N < 50). Second, we examined how
      contour maps based upon linear kriging were affected by the spatial structure of
      the given data set, as error estimation of contour maps appears to have received
      little attention in the entomological domain. We used weekly trap catches of the
      warehouse beetle, Trogoderma variabile, and the accuracy assessment was based
      upon data sets that had either a random spatial structure or were characterized
      by asymptotic spatial dependence. Asymptotic spatial dependence (typically
      described with a semivariogram analysis) means that trap catches at locations
      close to each other are more similar than trap catches at locations further
      apart. Trap catches were poorly predicted for data sets with a random spatial
      structure, while there was a significant correlation between observed and
      predicted trap catches for the spatially rearranged data sets. Therefore, for
      data sets with a random spatial structure we recommend visualization of the
      insect counts as scale-sized dots rather than as contour maps.

PMID- 14977095
TI  - Determining location and size of medical departments in a hospital network: a
      multiobjective decision support approach.
AB  - Decisions on the location and size of medical departments in a given hospital
      network are prime examples of priority setting in health care, which is an issue
      of growing political importance. As such decisions are regularly characterized by
      multiple and often conflicting objectives in real-life, this paper integrates the
      fields of hospital planning and multiobjective decision support. The proposed two
      phase solution procedure for our corresponding mathematical programming model
      does not require a priori preference information. Instead, it seeks efficient
      solutions by means of multiobjective tabu search in the first phase, while
      applying clustering in the second phase to allow the decision makers to
      interactively explore the solution space until the "best" configuration is
      determined. The real-world applicability of our approach is illustrated through a
      numerical example based on hospital data from Germany.

PMID- 14977097
TI  - Haplodiploidy, sex, and the evolution of pesticide resistance.
AB  - The assumption that males and females are equally tolerant to pesticides in
      haplodiploid arthropods led to the prediction that the evolution of resistance is
      faster in haplodiploid than in diploid arthropods. However, in this review, it
      was found that the ratio of male to female tolerance is substantially smaller in
      haplodiploid than in diploid arthropods, indicating that resistance alleles are
      not strongly up-regulated in haploid males. In addition, males were generally
      less tolerant than females in both haplodiploid and diploid arthropods. Factors
      such as sexual size dimorphism and sex-dependent selection may account for the
      lower tolerance in males than in females. Little among-population variation in
      the ratio of male to female tolerance was found in three species. Moreover, the
      tolerance ratio generally remained unchanged by selection for resistance to
      pesticides, although significant among-species variation was present within
      arthropod orders. This indicates that sexual dimorphism in pesticide tolerance
      evolves at a slower rate than resistance to pesticides. Simulations considering
      between-sex differences in pesticide tolerance showed that resistance evolution
      can be slower in haplodiploids than in diploids. Recessive resistance, low male
      tolerance to pesticides, fitness costs expressed in males, and the use of refuges
      contributed in substantially delaying the evolution of resistance in haplodiploid
      arthropods. These findings cast a new perspective on the evolution of pesticide
      resistance in haplodiploid herbivores and natural enemies.

PMID- 14977098
TI  - American foulbrood and African honey bees (Hymenoptera: Apidae).
AB  - We have taken samples of honey from individual beekeepers (N = 64), and of
      domestic (N = 35) and imported honey (N = 15) retailed in supermarkets in several
      sub-Saharan countries and cultivated these samples for Paenibacillus larvae
      subsp. larvae Heyndrickx et al. causing American foulbrood in honey bee colonies.
      The results are compared with samples of similar backgrounds and treated the same
      way but collected in Sweden (N = 35). No P. larvae subsp. larvae spores were
      found in any honey produced in Africa south of the Sahara although honey imported
      into this region frequently contains the pathogen. Swedish honey frequently
      contains P. larvae subsp. larvae spores although the general level of visibly
      infected bee colonies is low (roughly 0.5%). The results suggest that large parts
      of Africa may be free from American foulbrood. Behavioral studies (hygienic
      behavior) on Apis mellifera subsp. scutellata Lepeletier in Zimbabwe suggest that
      hygienic behavior of African bees could influence the apparent low level, or even
      absence of American foulbrood in large parts of Africa.

PMID- 14977099
TI  - Efficacy of modified hive entrances and a bottom screen device for controlling
      Aethina tumida (Coleoptera: Nitidulidae) infestations in Apis mellifera
      (Hymenoptera: Apidae) colonies.
AB  - This study was designed to test whether hive entrances reduced with polyvinyl
      chloride pipe reduce the ingress of Aethina tumida Murray into Apis mellifera L.
      colonies and whether screen-mesh bottom boards alleviate side effects associated
      with restricted entrances. Forty-eight colonies distributed equally between two
      locations each received one of six experimental treatments: 1) conventional solid
      bottom board and open entrance, 2) ventilated bottom board and open entrance, 3)
      conventional bottom and 1.9-cm-i.d. pipe entrance, 4) conventional bottom and 3.8
      cm pipe entrance, 5) screen bottom and 1.9-cm pipe entrance, and 6) screen bottom
      and 3.8-cm pipe entrance. Results were inconsistent between apiaries. In apiary
      1, colonies with 3.8-cm pipe entrances had fewer A. tuzmida than colonies with
      open entrances, but this benefit was not apparent in apiary 2. Pipe entrances
      tended to reduce colony and brood production in both apiaries, and these losses
      were only partly mitigated with the addition of screened bottom boards. Pipe
      entrances had no measurable liability concerning colony thermoregulation. There
      were significantly fewer frames of adult A. mellifera in colonies with 3.8- or
      1.9-cm pipe entrances compared with open entrances but more in colonies with
      screens. There were more frames of pollen in colonies with open or 3.8-cm pipe
      entrances than 1.9-cm entrances. We conclude that the efficacy of reduced hive
      entrances in reducing ingress of A. tumida remains uncertain due to observed
      differences between apiaries. Furthermore, there were side effects associated
      with restricted entrances that could be only partly mitigated with screened
      bottom boards.

PMID- 14977100
TI  - Evaluation of oils and microbial pathogens for control of lepidopteran pests of
      sweet corn in New England.
AB  - Vegetable and mineral oil, Beauveria bassiana (Balsamo) and Bacillus
      thuringiensis subsp. kurstaki Berliner were evaluated for control of Ostrinia
      nubilalis (Hubner) (Lepidoptera: Pyralidae), Helicoverpa zea (Boddie)
      (Lepidoptera: Noctuidae) and Spodoptera frugiperda (J. E. Smith) (Lepidoptera:
      Noctuidae) in sweet corn (Zea mays L.). Field experiments in Maine and
      Massachusetts during 1993 and 1994 evaluated oils and pathogens singly or in
      combinations, using a single application directly to the top of the silk channel,
      immediately after pollination. Mineral oil alone provided equal (1993) or better
      (1994) control compared with corn oil. In both years, mineral or corn oil plus B.
      thuringiensis resulted in 93-98% marketable ears, compared with 48-52% marketable
      ears in untreated plots. In three factorial experiments with B. bassiana, B.
      thuringiensis and corn oil, B. bassiana at 5 x 10(7) conidia per ear provided
      little or no control while B. thuringiensis and corn oil provided significant
      though not always consistent control of all three species. The combination of B.
      thuringiensis and corn oil provided the largest and most consistent reduction in
      numbers of larvae and feeding damage to ears.

PMID- 14977101
TI  - Increased mortality of gypsy moth Lymantria dispar (L.) (Lepidoptera:
      Lymantriidae) exposed to gypsy moth nuclear polyhedrosis virus in combination
      with the phenolic gycoside salicin.
AB  - Second instar gypsy moth, Lymantria dispar (L.) (Lepidoptera: Lymantriidae),
      larvae suffered significantly greater mortality from aerially applied gypsy moth
      nuclear polyhedrosis virus (Gypchek) when the virus was consumed on quaking
      aspen, Populus tremuloides Michx., versus red oak, Quercus spp. L., foliage.
      Laboratory assays in which various doses of Gypchek and salicin (a phenolic
      glycoside present in aspen foliage) were tested in combination demonstrated that
      salicin significantly increased total larval mortality and lowered the LD50
      estimates (dose of Gypchek that resulted in 50% population mortality) for the
      virus, although not significantly. While salicin did not impact larval survival
      in the absence of Gypcek, it did act to significantly deter feeding when it was
      present in high concentrations (up to 5.0%) within the treatment formulations.
      The enhanced activity of Gypchek in the presence of salicin is similar to prior
      reports of enhanced activity of the bacterial pathogen Bacillus thuringiensis
      when consumed concurrently with phenolic glycosides commonly present in aspen
      foliage. The enhancement of viral activity is in contrast to the inhibitory
      effects on the virus reported for another common group of phenolic compounds,
      tannins.

PMID- 14977102
TI  - Effect of tinopal LPW on the insecticidal properties and genetic stability of the
      nucleopolyhedrovirus of Spodoptera exigua (Lepidoptera: Noctuidae).
AB  - The influence of an optical brightener, Tinopal LPW, on the activity of a
      purified genotype of the nucleopolyhedrovirus (SeMNPV) of the beet armyworm,
      Spodoptera exigua (Hubner), was determined in second to fifth instar (L2-L5) S.
      exigua. When mixed with viral occlusion bodies (OB) 1% Tinopal LPW significantly
      reduced the median lethal dose (LD50) of the virus in all instars compared with
      insects treated with SeMNPV alone. Levels of enhancement, as determined by LD50
      values, ranged from 2.6- to 580-fold, depending on the instar. The greatest
      enhancement occurred on the two later instars, L4 (70-fold) and L5 (580-fold),
      which show a much higher resistance to SeMNPV infection than earlier instars. The
      median time to death (MTD) values were not significantly different in any instar
      among larvae treated with SeMNPV + Tinopal LPW and those treated with SeMNPV
      alone. Larval development in SeMNPV + Tinopal LPW treated larvae was retarded, in
      second and fourth instars, compared with controls or larvae treated with SeMNPV
      alone. The OB yields from SeMNPV treated larvae were almost 1.6-fold greater in
      second instars (9.3 x 10(6) OBs/larvae), and 1.9-fold greater in fourth instars
      (1.9 x 10(8) OBs/larvae), than those obtained in larvae treated with SeMNPV +
      Tinopal LPW. The addition of 1% Tinopal LPW to the virus suspension did not alter
      the genotypic composition of viral progeny during four successive passages of the
      virus.

PMID- 14977103
TI  - Evaluation of predatory mite (Acari: Phytoseiidae) releases to suppress spruce
      spider mites, Oligonychus ununguis (Acari: Tetranychidae), on juniper.
AB  - A laboratory trial evaluated four phytoseiid species for their potential as
      biological control agents of spruce spider mite, Oligonychus ununguis (Jacobi)
      (Acari: Tetranychidae). An augmentative biological control approach, using the
      predatory mites Neoseiulus fallacis Garman and Galendromus occidentalis Nesbitt
      (Acari: Phytoseiidae), was evaluated for reducing pest mite densities and injury,
      and economic costs on Juniperus chinensis 'Sargentii' A. Henry (Cupressaceae) in
      an outdoor nursery. Sequential releases of predator species, individually and in
      combination, were tested and compared with two commonly used miticides, a low
      toxicity miticide, horticultural oil, and a conventional miticide, hexythiazox.
      Timing of treatments was based on grower-determined need, and predator release
      rates were based on guidelines in literature received from producers of
      beneficial organisms. Predator releases were more expensive and provided less
      effective suppression of spruce spider mites, resulting in greater spider mite
      injury to plants, compared with conventional pesticides. However, spider mite
      damage to plants did not differ in an economically meaningful way between
      treatments. Unsatisfactory levels of control seem related to under estimations of
      actual spider mite abundance based on grower perceptions and the beat sampling
      technique used to estimate predator release rates. These data suggest that when
      initial populations of spruce spider mite are high, it is unlikely that
      sequential releases of predator species, individually or in combination, will
      suppress spider mite populations. In this trial, augmentative biological control
      control was 2.5-7 times more expensive than chemical controls.

PMID- 14977104
TI  - Responses of Lipolexis oregmae (Hymenoptera: Aphidiidae) to different instars of
      Toxoptera citricida (Homoptera: Aphididae).
AB  - The effects of host instar of Toxoptera citricida Kirkaldy (Homoptera: Aphididae)
      on the performance of the parasitoid Lipolexis oregmae (Gahan) (Hymenoptera:
      Aphidiidae), originally Lipolexis scutellaris Mackauer, were evaluated in an
      effort to increase basic knowledge of this host-parasitoid association, improve
      field sampling methods, and potentially predict the success of parasitism in the
      field. L. oregmae was able to oviposit and develop in all four instars of T.
      citricida; however, there are differences in the quality of different host
      instars. Although second-instar hosts produce more L. oregmae progeny and a
      higher female-biased sex ratio, fourth-instar hosts produce L. oregmae progeny
      that are larger and have a higher realized fecundity. However, fourth-instar
      hosts require a longer handling time and expose the parasitoid female to more
      aphid behavioral defenses than do second-instar hosts. Additionally, results
      suggest that fourth-instar hosts may elicit a physiological immune response to
      parasitism; when aphids were observed being stung once, the number of L. oregmae
      larvae present on dissection after 4 d and the number of eclosed adults was lower
      in fourth- than in second-instar hosts. Pupal mortality of L. oregmae was also
      higher in fourth-instar hosts compared with second-instar hosts. The results of
      this study confirm that L. oregmae has a high reproductive rate and low incidence
      of incomplete parasitization on this host and is one of only a few natural
      enemies able to complete development in all instars of the brown citrus aphid in
      Florida.

PMID- 14977105
TI  - Nonhost status of Citrus sinensis cultivar valencia and C. paradisi cultivar ruby
      red to Mexican Anastrepha fraterculus (Diptera: Tephritidae).
AB  - Anastrepha fraterculus (Wiedemann) is recognized as a pest of citrus, apples, and
      blackberries in South America. In Mexico, it is mainly found in fruit of the
      family Myrtaceae and has never been reported infesting citrus. Here, we sought to
      determine whether females stemming from Mexican A. fraterculus populations
      (collected in the state of Veracruz) would lay eggs in 'Valencia' oranges and
      'Ruby Red' grapefruit and, if so, whether larvae would hatch and develop. We
      worked under laboratory and seminatural conditions (i.e., gravid females released
      in fruit-bearing, bagged branches in a commercial citrus grove) and used
      Anastrepha ludens (Loew), a notorious pest of citrus, as a control species. Under
      laboratory conditions, A. ludens readily accepted both oranges and grapefruit as
      oviposition substrates, but A. fraterculus rarely oviposited in these fruit (but
      did so in guavas, a preferred host) and no larvae ever developed. Eggs were
      deposited in the toxic flavedo (A. fraterculus) and nontoxic albedo (A. ludens)
      regions. Field studies revealed that, as was the case in the laboratory, A.
      fraterculus rarely oviposited into oranges or grapefruit and that, when such was
      the case, either no larvae developed (oranges) or of the few (13) that developed
      and pupated (grapefruit), only two adults emerged that survived 1 and 3 d,
      respectively (5-17% of the time necessary to reach sexual maturity). In sharp
      contrast, grapefruit exposed to A. ludens yielded up to 937 pupae and adults
      survived for >6 mo. Therefore, the inability of Mexican A. fraterculus to
      successfully develop in citrus renders the status of Mexican A. fraterculus as a
      pest of citrus in Mexico as unsubstantiated.

PMID- 14977106
TI  - Acoustic identification and measurement of activity patterns of white grubs in
      soil.
AB  - Activity patterns of Phyllophaga crinita (Burmeister), Phyllophaga congrua
      (LeConte), Phyllophaga crassissima (Blanchard), and Cyclocephala lurida (Bland)
      grubs were monitored with acoustic sensors in small pots of bluegrass, Poa
      arachnifera Torr, at varying and constant temperatures over multiple-day periods.
      Experienced listeners readily distinguished three types of sound with distinct
      differences in frequency and temporal patterns, intensities, and durations. Of
      approximately 3,000 sounds detected from P. crinita larvae, 7% were identifiable
      as snaps, with large amplitudes and short durations typically associated with
      root breakage or clipping activity. Approximately 60% were identifiable as
      rustles, suggestive of surfaces sliding or rubbing past each other during general
      movement activity. Another 2% of sounds contained patterns of repeated pulses
      suggestive of surfaces scraping across a pointed ridge. The remaining 31% had
      spectral or temporal patterns that fell outside the ranges of easily recognizable
      sound types. Because the behavioral significance of the different sound types has
      not yet been fully established, the classified and unclassified sounds were
      pooled together in analyses of the effects of species, temperature, weight, and
      time of day. Grubs of all four species produced detectable sounds at rates that
      increased with temperature [0.45 sounds/((min)(degrees C))] and larval weight
      [6.3 sounds/((min)(g))]. Mean sound rates were independent of species and time of
      day. At temperatures <9 degrees C, mean sound rates fell below the typical levels
      of background noise observed under field conditions. This reduced activity at low
      temperatures is likely to reduce the effectiveness of acoustic monitoring in the
      field in cold weather. The consistency of results obtained in these tests over
      multiple-day periods suggests that acoustic systems have potential as tools for
      nondestructive monitoring of the efficacy of insect management treatments as well
      as for biological and ecological studies.

PMID- 14977107
TI  - Recent Mediterranean fruit fly (Diptera: Tephritidae) infestations in Florida--a
      genetic perspective.
AB  - Microsatellite and mitochondrial DNA (mtDNA) variability data were used to study
      infestations of the Mediterranean fruit fly, Ceratitis capitata (Wiedemann) in
      Florida in 1997 and 1998. A total of 132 flies collected in monitoring traps or
      as larvae removed from fruit were examined at three polymorphic mtDNA restriction
      sites and two microsatellite loci. All of the flies sampled in Florida in 1997
      displayed the mitochondrial AAB haplotype and represent a novel introduction of
      Mediterranean fruit flies into the state. All flies collected in central Florida
      in 1998 also displayed the AAB haplotype. Microsatellite analysis of these
      specimens from 1998 detected only alleles that were present in 1997. These
      results strongly indicate that the 1998 Florida outbreaks were derived from the
      Florida populations from the previous year. According to our analyses, the
      Mediterranean region is the most likely source for the 1997 Florida infestation.
      Flies from a small outbreak in Miami Springs, Dade County, FL, early in 1998 had
      a different mtDNA haplotype, characterized by the AAC restriction pattern.
      Microsatellites of these specimens showed significant differences in their
      allelic distribution from AAB flies, indicating an origin from a separate source
      population. South America is the most likely source for the Miami Springs flies.

PMID- 14977108
TI  - Improved attractants for Mediterranean fruit fly, Ceratitis capitata (Wiedemann):
      responses of sterile and wild flies to (-) enantiomer of ceralure B1.
AB  - Tests were conducted on wild Mediterranean fruit flies, Ceratitis capiata
      (Wiedemann), in Hawaii, Italy, and Kenya, and on sterile released flies in
      Florida and California with a new male attractant, (-)-ceralure B1. Compared on
      an equal dosage basis, Mediterranean fruit fly males were significantly more
      attracted to the (-)-ceralure B1 than to trimedlure in each of the sites tested
      except for California. Compared with the standard commercial 2 g trimedlure plug,
      10 mg applied on cotton wicks (Kauai) was as attractive to wild males as
      trimedlure after the first 2 d of the test but not after 7 d. At a dose of 40 mg
      (50 times less than in the 2-g plug), the (-)-ceralure B1 was significantly more
      attractive to male flies than the 2-g trimedlure plug for the first week of
      service (Florida) but not after 2 wk. Studies using released sterile flies in
      Florida confirm our previous work on the improved attraction of (-)-ceralure B1
      (40 mg) over trimedlure. However, this trend did not hold up in a single test
      conducted in a residential area in California that did not show a significant
      difference in attraction using 20 mg of compound. Future refinements in synthesis
      and costs of this compound and increased availability and testing will be needed
      before any final evaluation in the field can be carried out.

PMID- 14977109
TI  - Radiation biology and inherited sterility in false codling moth (Lepidoptera:
      Tortricidae).
AB  - False codling moth, Cryptophlebia leucotreta (Meyrick), male and female mature
      pupae and newly emerged adults were treated with increasing doses of gamma
      radiation and either inbred or out-crossed with fertile counterparts. For newly
      emerged adults, there was no significant relationship between dose of radiation
      and insect fecundity when untreated females were mated to treated males (N female
      by T male). However, fecundity of treated females mated to either untreated (T
      female by N male) or treated males (T female by T male) declined as the dose of
      radiation increased. A similar trend was observed when mature pupae were treated.
      The dose at which 100% sterility was achieved in treated females mated to
      untreated males (T female by N male) for both adults and pupae was 200 Gy. In
      contrast, newly emerged adult males treated with 350 Gy still had a residual
      fertility of 5.2% when mated to untreated females, and newly emerged adult males
      that were treated as pupae had a residual fertility of 3.3%. Inherited effects
      resulting from irradiation of parental (P1) males with selected doses of
      radiation were recorded for the F1 generation. Decreased F1 fecundity and
      fertility, increased F1 mortality during development, and a significant shift in
      the F1 sex ratio in favor of males was observed when increasing doses of
      radiation were applied to the P1 males.

PMID- 14977110
TI  - Nontarget insects captured in fruit fly (Diptera: Tephritidae) surveillance
      traps.
AB  - Traps baited with synthetic lures (ammonium acetate and putrescine) captured as
      many Mexican fruit flies as the traditional torula yeast/borax slurry, but with
      far fewer (ratio 5:1) nontarget insects. Ninety percent of the nontarget insects
      were dipterans. Consequently, neither trap is efficacious against other citrus
      pests, which are mainly Hemiptera or Lepidoptera. Although the nontarget catch is
      sometimes referred to as "trash," many nontarget insects are beneficials,
      including predators and parasites (especially tachinids). The traps with
      synthetic lures killed fewer of these beneficials by a ratio of 4:1 compared with
      the yeast-baited traps. Certain taxa, notably the chrysopids and halictid bees,
      exhibited a somewhat greater preference (10 and 50%, respectively) for the
      synthetic lures. Overall, with regard to the deployment of the newer baits, the
      threat to predators, parasites, and pollinators was found to be negligible, and
      certainly much less than that posed by the traditional traps.

PMID- 14977111
TI  - Use of transgenic plants to measure insect herbivore movement.
AB  - Use of ingested transgenic corn tissue as a marker for measuring movement of
      adult Diabrotica virgifera virgifera (LeConte) (Coleoptera: Chrysomelidae;
      western corn rootworm) was investigated. Laboratory observations of beetles
      feeding on corn foliage, pollen, silks, or soybean foliage provided background on
      feeding patterns. The interval between food consumption and its appearance in
      feces (gut passage time) ranged from 102.7 +/- 11 min for soybean foliage to 56.7
      +/- 2.9 min for corn silks. In a laboratory assay, protein expression tests
      identified the presence of Cry3Bb1 protein inside 50% of adult D. virgifera for
      up to 16 h after they had last consumed Cry3Bb1 protein-expressing corn silks
      from 'YieldGard Rootworm' corn plants (Monsanto Co.). Cry3Bb1 protein could not
      be detected by 32 h postfeeding. The proportion of Cry3Bb1 protein-positive
      beetles declined linearly with increasing time since feeding on 'YieldGard
      Rootworm' tissue. Approximately 20% of adult D. virgifera collected near
      'YieldGard Rootworm' corn plots tested positive for Cry3Bb1 protein, indicating
      'YieldGard Rootworm' tissue consumption within the last 16-32 h. Based on a 16-
      to 32-h postfeeding detection interval for Cry3Bb1 protein and the distance
      between 'YieldGard Rootworm' sources and sites where Cry3Bb1-positive insects
      were collected, 85.3% of males and females moved < or = 4.6-9.1 m/d through R2-R3
      stage corn. Among Cry3Bb1-positive adults that left corn and were captured in an
      adjacent soybean field, 86.4% of males and 93.1% of females moved < or = 4.6-9.1
      m/d through soybean. Detection of transgenic plant tissues in mobile insect
      herbivores is a novel application of biotechnology to the study of insect
      movement.

PMID- 14977112
TI  - In-field labeling of western corn rootworm adults (Coleoptera: Chrysomelidae)
      with rubidium.
AB  - Field and laboratory studies were conducted in 2000 and 2001 to determine the
      feasibility of mass marking western corn rootworm adults, Diabrotica virgifera
      virgifera LeConte, with RbCl in the field. Results showed that application of
      rubidium (Rb) in solution to both the soil (1 g Rb/plant) and whorl (1 g
      Rb/plant) of corn plants was optimal for labeling western corn rootworm adults
      during larval development. Development of larvae on Rb-enriched corn with this
      technique did not significantly influence adult dry weight or survival. Rb was
      also highly mobile in the plant. Application of Rb to both the soil and the whorl
      resulted in median Rb concentrations in the roots (5,860 ppm) that were 150-fold
      greater than concentrations in untreated roots (38 ppm) 5 wk after treatment.
      Additionally, at least 90% of the beetles that emerged during the first 3 wk were
      labeled above the baseline Rb concentration (5 ppm dry weight) determined from
      untreated beetles. Because emergence was 72% complete at this time, a significant
      proportion of the population had been labeled. Results from laboratory
      experiments showed that labeled beetles remained distinguishable from unlabeled
      beetles for up to 4 d postemergence. The ability to efficiently label large
      numbers of beetles under field conditions and for a defined period with virtually
      no disruption of the population provides an unparalleled opportunity to conduct
      mark-recapture experiments for quantifying the short-range, intrafield movement
      of adult corn rootworms.

PMID- 14977113
TI  - Phenology and density of balsam twig aphid, Mindarus abietinus Koch (Homoptera:
      Aphididae) in relation to bud break, shoot damage, and value of fir Christmas
      trees.
AB  - The balsam twig aphid, Mindarus abietinus Koch (Homoptera: Aphididae), is a major
      insect pest of balsam and Fraser fir grown for Christmas trees. Our objectives in
      this study were to 1) monitor the phenology of A. abietinus in fir plantations;
      2) assess relationships among M. abietinus density, tree phenology, and damage to
      tree foliage; and 3) develop an esthetic injury level for M. abietinus on
      Christmas trees. We monitored phenology of M. abietinus and fir trees on three
      commercial Christmas tree plantations in central and northern Lower Michigan for
      3 yr (1999-2001). Phenology of M. abietinus fundatrices and sexuparae was
      strongly correlated with accumulated degree-days (DD) base 10 degrees C.
      Fundatrices matured by approximately 83 DD(10 degrees C) and sexuparae were first
      observed at approximately 83-111 DD(10 degrees C). Trees that broke bud
      approximately 1 wk later than other trees in the same field escaped M. abietinus
      damage and shoot expansion rate in spring was generally positively correlated
      with M. abietinus damage. Retail customers surveyed at a choose-and-cut Christmas
      plantation in 2 yr did not consistently differentiate between similarly sized
      trees with no, light, and moderate M. abietinus damage, but heavy damage (>50%
      damaged shoots) did affect customer perception. Similarly, when wholesale grades
      were assigned, the high quality Grade 1 trees had up to 40% shoot damage, whereas
      Grade 2 trees had 32-62% shoot damage. Two trees ranked as unsaleable had sparse
      canopies and distorted needles on 42% to almost 100% of the shoots.

PMID- 14977114
TI  - Acoustic estimation of infestations and population densities of white grubs
      (Coleoptera: Scarabaeidae) in turfgrass.
AB  - Incidental sounds produced by Phyllophaga crinita (Burmeister) and Cyclocephala
      lurida (Bland) (Coleoptera: Scarabaeidae) white grubs were monitored with single-
      and multiple-sensor acoustic detection systems in turf fields and golf course
      fairways in Texas. The maximum detection range of an individual acoustic sensor
      was measured in a greenhouse as approximately the area enclosed in a 26.5-cm
      diameter perimeter (552 cm2). A single-sensor acoustic system was used to rate
      the likelihood of white grub infestation at monitored sites, and a four-sensor
      array was used to count the numbers of white grubs at sites where infestations
      were identified. White grub population densities were acoustically estimated by
      dividing the estimated numbers of white grubs by the area of the detection range.
      For comparisons with acoustic monitoring methods, infestations were assessed also
      by examining 10-cm-diameter soil cores collected with a standard golf cup-cutter.
      Both acoustic and cup-cutter assessments of infestation and estimates of white
      grub population densities were verified by excavation and sifting of the soil
      around the sensors after each site was monitored. The single-sensor acoustic
      method was more successful in assessing infestations at a recording site than was
      the cup-cutter method, possibly because the detection range was larger than the
      area of the soil core. White grubs were recovered from >90% of monitored sites
      rated at medium or high likelihood of infestation. Infestations were successfully
      identified at 23 of the 24 sites where white grubs were recovered at densities
      >50/m2, the threshold for economic damage. The four-sensor array yielded the most
      accurate estimates of the numbers of white grubs in the detection range, enabling
      reliable, nondestructive estimation of white grub population densities. However,
      tests with the array took longer and were more difficult to perform than tests
      with the single sensor.

PMID- 14977115
TI  - Field trials of spinosad as a replacement for naled, DDVP, and malathion in
      methyl eugenol and cue-lure bucket traps to attract and kill male oriental fruit
      flies and melon flies (Diptera: Tephritidae) in Hawaii.
AB  - Spinosad was evaluated in Hawaii as a replacement for organophosphate
      insecticides (naled, dichlorvos [DDVP], and malathion) in methyl eugenol and cue
      lure bucket traps to attract and kill oriental fruit fly, Bactrocera dorsalis
      Hendel, and melon fly, B. cucurbitae Coquillett, respectively. In the first and
      second methyl eugenol trials with B. dorsalis, naled was in the highest rated
      group for all evaluation periods (at 5, 10, 15, and 20 wk). Spinosad was equal to
      naled at 5 and 10 wk during both trials 1 and 2, and compared favorably with
      malathion during trial 2. During the first cue-lure trial with B. cucurbitae,
      naled and malathion were in the top rated group at 5, 10, 15, and 20 wk. Spinosad
      was equal to naled at 5 wk. During the second cue-lure trial, spinosad and naled
      were both in the top rated group at 10, 15, and 20 wk. Use of male lure traps
      with methyl eugenol or cue-lure had no effect on attraction of females into test
      areas. Our results suggest that spinosad, although not as persistent as naled or
      malathion, is safer to handle and a more environmentally friendly substitute for
      organophosphate insecticides in methyl eugenol and cue-lure traps for use in B.
      dorsalis and B. cucurbitae areawide integrated pest management programs in
      Hawaii.

PMID- 14977116
TI  - Efficacy of VectoBac (Bacillus thuringiensis variety israelensis) formulations
      for mosquito control in Australia.
AB  - Laboratory bioassays were conducted on the efficacy of a water-dispersible
      granule (WG) formulation of Bacillus thuringiensis variety israelensis (VectoBac
      WG; active ingredient [AI]: 3,000 Bti international toxic units [ITU]/mg) against
      third instars of six common Australian mosquito species, Aedes aegypti (L.),
      Ochlerotatus vigilax (Skuse), Ochlerotatus notoscriptus (Skuse), Culex sitiens
      Wiedemann, Culex annulirostris Skuse, and Culex quinquefasciatus Say. The normal
      model for log-linear mortality data was used to determine laboratory 48-h LC50
      and LC95 values. The target mosquito species tested were extremely sensitive to
      the VectoBac WG formulation, with the most sensitive species (Cx. annulirostris
      and Cx. quinquefasciatus, LC95 value of 0.019 ppm) being twice as susceptible as
      the most tolerant (Oc. notoscriptus, LC95 value of 0.037 ppm). Cx. annulirostris
      was selected as a target species for a small-plot evaluation of VectoBac WG and
      VectoBac 12 aqueous solution (AS) ([AI]: 1,200 Bti ITU/mg) efficacy over time, in
      freshwater in southeastern Queensland, Australia. Replicated cohorts of caged
      third instars were exposed weekly to six concentrations of WG formulation (0.004
      0.13 ppm) and three concentrations of the 12AS formulation (0.04-0.13 ppm). In
      water with high organic content, treatment concentrations of 0.008 ppm WG and
      0.04 ppm 12AS and above produced significant larval control (> or = 96%) at 48 h
      posttreatment, with no residual control at week 1. Water quality was not affected
      by treatment with either formulation.

PMID- 14977117
TI  - Tillage impacts cereal-aphid (Homoptera: Aphididae) infestations in spring small
      grains.
AB  - We compared infestation levels of cereal aphids (Homoptera: Aphididae) in spring
      seeded wheat and barley grown with and without preplant tillage for 8 site yr in
      eastern South Dakota. Crop residue covered approximately 25% of the soil surface
      with preplant tillage, whereas without preplant tillage 50% or more of surface
      residue was conserved. Rhopalosiphum padi (L.) comprised nearly 90% of all cereal
      aphids sampled, and R. maidis (Fitch), Schizaphis graminum (Rondani), and
      Sitobion avenae (F.) collectively comprised the remainder. R. padi routinely
      infested lower parts of tillers and were generally concealed by surface residue
      in plots with no preplant tillage. Across 7 site yr, R. padi were more abundant
      in plots with no preplant tillage than with preplant tillage (272.6 +/- 54.4
      versus 170.1 +/- 37.2 aphid days per 25 tillers). However, in comparisons at
      individual site years, R. padi were greater in no-preplant tillage plots only
      once. For all cereal-aphid species combined, infestations were greater in plots
      with no preplant tillage for 1 of 8 site yr, but did not differ with tillage when
      compared across all site years. Cereal aphids were never more abundant in plots
      with preplant tillage. Our results show that conservation tillage leads to
      greater infestations of R. padi in spring small grains, as increased surface
      residue provides a favorable microhabitat for this aphid.

PMID- 14977118
TI  - Nutrient uptake of rice roots in response to infestation of Nilaparvata lugens
      (Stal) (Homoptera: Delphacidae).
AB  - This study investigated the uptake of three macronutrients, including nitrogen
      (N), phosphorus (P), and potassium (K), by rice roots in response to different
      infestation levels of Nilaparvata lugens (Stal) (Homoptera: Delphacidae).
      Hydroponics experiments were conducted on the rice variety 'Zhendao 2'
      (moderately resistant to Tryporyza incertulas, Lepidoptera: Pyralidae) and the
      variety 'Xiushui 63' (susceptible to N. lugens). In 'Zhendao 2', N. lugens
      infestation significantly influenced the uptake of P and K but not N, with P and
      K uptake decreasing as the duration of N. lugens infestation increased. In
      'Xiushui 63', N. lugens infestation influenced N, P, and K uptake to a different
      degree, depending on the infestation level, in which infestation for 2, 4, 6, and
      8 d at a density of 60 nymphs did not affect N uptake, but such infestation
      levels significantly influenced the uptake of P and K. After the removal of N.
      lugens from rice plants, the N uptake recovered from infestation faster than that
      for P and K in the variety 'Zhendao 2', whereas the recovery rate of K uptake was
      faster than that for N and P in the variety 'Xiushui 63'. The recovery rate of
      the nutrient uptake was negatively correlated to the density and duration of
      infestation. The experimental results demonstrated that N, P, and K uptake of
      rice roots were largely not influenced by N. lugens infestation when the pest
      density was controlled below 15 nymphs per hill. This infestation level was in
      agreement with the proposed economic thresholds for control measures against the
      N. lugens infestation on rice plants.

PMID- 14977119
TI  - Predatory fauna in cornfields and response to imidacloprid seed treatment.
AB  - The composition and abundance of predatory fauna in corn, Zea mays L., were
      studied by field visual sampling and pitfall traps over a 5-yr period. In visual
      samplings, the most abundant groups were Araneae, Heteroptera, Carabidae,
      Coccinellidae, and Staphylinidae, whereas the prevalent predators caught in
      pitfall traps belonged to Carabidae, Araneae, Dermaptera, and Opilionidae. The
      most abundant species or genera in the prevalent groups, except in Arachnida,
      were identified. Application of the insecticide imidacloprid as a seed dressing
      is common in the study area to prevent wireworm and cutworm damage. By comparing
      predator composition and abundance in treated and untreated cornfields during the
      5 yr, we assessed the impact of imidacloprid seed treatment on predatory fauna.
      Among the prevalent predator groups found in visual sampling, Araneae,
      Coccinellidae, and Staphylinidae were not affected by the imidacloprid treatment,
      whereas Carabidae was only moderately affected in one of the 5 yr studied. On the
      contrary, Heteroptera was more drastically reduced by the imidacloprid, but the
      effect varied with the year. Incidence of European corn borer, Ostrinia nubilalis
      (Hubner), may be increased as result of such heteropteran reduction. In pitfall
      traps, only Staphylinidae resulted in lower numbers as consequence of the
      treatment, whereas the rest of the most abundant predator groups, Carabidae,
      Araneae, Dermaptera, Opilionidae, Trombididae, and Heteroptera, were not caught
      in significantly different numbers in treated or untreated plots.

PMID- 14977120
TI  - Phenology of Lygus lineolaris (Hemiptera: Miridae) in Minnesota June-bearing
      strawberries: comparison of sampling methods and habitats.
AB  - Field studies were conducted in southeastern Minnesota from 2000 to 2002 to
      determine the phenology of Lygus lineolaris in various habitats and to compare
      yellow and white sticky traps as a sampling method for adult L. lineolaris.
      Strawberry fields were sampled for L. lineolaris adults using yellow sticky
      traps, and nymphs were sampled using the standard white pan beat method. Adult L.
      lineolaris abundance in alfalfa, an adjacent fence-row, and a wooded habitat were
      also compared. The nonlinear relationship between cumulative trap catch and
      cumulative degree-days was modeled with a two-parameter cumulative Weibull
      function to predict early-season adult capture using yellow sticky traps. Adult
      L. lineolaris were detected in bearing-year strawberries at the onset of
      vegetative growth in all years. Yellow sticky traps caught significantly higher
      densities of adult L. lineolaris than white sticky traps. The Weibull model
      predicted 50% capture at 10 DD (>12.4 degrees C), which corresponds to the
      vegetative strawberry growth stage. L. lineolaris nymphs were not detected until
      the blossom stage. Alfalfa harbored significantly higher densities of L.
      lineolaris than other habitats during early-season sampling (i.e., March-June).
      Late-season sampling (July-September) revealed significantly higher densities in
      bearing-year strawberries. These results suggest that monitoring at the onset of
      vegetative growth, using yellow sticky traps, will be an efficient method for
      detecting early L. lineolaris adult activity.

PMID- 14977121
TI  - Techniques for monitoring cranberry tipworm (Diptera: Cecidomyiidae) in rabbiteye
      and southern highbush blueberries.
AB  - Several monitoring techniques were evaluated for their effectiveness, based on
      the highest mean captures of cranberry tipworm, Dasineura oxycoccana (Johnson),
      in detecting D. oxycoccana in rabbiteye, Vaccinium ashei Reade, and southern
      highbush, V. corymbosum L. x V. darrowi Camp, blueberry plantings. There were no
      significant differences in captures of D. oxycoccana adults on unbaited sticky
      board traps, regardless of color (yellow, white, green, or blue). In a separate
      experiment, three monitoring techniques, yellow unbaited sticky boards,
      larval/adult emergence from infested buds, and bud dissection, were evaluated for
      detecting D. oxycoccana, eggs, larvae, and adults. In total, four bud types were
      examined, including rabbiteye floral, rabbiteye leaf, southern highbush floral,
      and southern highbush leaf. The emergence monitoring technique detected
      significantly more D. oxycoccana adults than the other techniques evaluated.
      Emergence and dissection techniques performed equally well for detecting D.
      oxycoccana larvae. Dissection was the only technique capable of detecting D.
      oxycoccana eggs. Overall, the highest numbers of D. oxycoccana eggs were detected
      in southern highbush leaf buds. However, larval infestation was lower for
      southern highbush leaf buds compared with other bud types sampled. Hypotheses to
      explain this phenomenon are discussed. The fewest number of eggs was recorded for
      southern highbush flower buds, potentially because these buds develop before peak
      emergence of D. oxycoccana. Managing D. oxycoccana in infested plantings can be
      improved by incorporating monitoring techniques, specifically bud dissection to
      search for eggs, that will aid growers in making timely insecticide applications.

PMID- 14977122
TI  - Field evaluation of the bait toxicant chlorfluazuron in eliminating Coptotermes
      acinaciformis (Froggatt) (Isoptera: Rhinotermitidae).
AB  - Two aspects of the Exterra Termite Interception and Baiting System (Ensystex,
      Fayetteville, NC) were evaluated in a field experiment using 13 termite mounds
      near Townsville, Australia. First, a cellulose-acetate powder containing either
      0.05% wt:wt or 0.25% wt:wt chlorfluazuron (Requiem, Ensystex, Fayetteville, NC)
      was tested for its efficacy in eliminating colonies of the xylophagous mound
      building subterranean termite Coptotermes acinaciformis (Froggatt). The moist
      bait matrix was replenished during the first inspection of 10 mounds (five mounds
      by two treatments) used in the experiment. Second, a single application of the
      moist bait matrix was used on three additional mounds to test termite responses
      and the effectiveness of 0.25% wt:wt chlorfluazuron. Although there was no
      evidence of repellence, there was little removal of replenished bait. Five
      colonies were eliminated by 0.05% wt:wt chlorfluazuron and five colonies by 0.25%
      wt:wt chlorfluazuron: another colony was moribund, and elimination appeared
      imminent. Colony decline was first suspected some 12 wk after bait application,
      and colony elimination was confirmed, by destructive sampling, about 5 wk later.
      Colony elimination may have occurred within 12 wk. One colony was an anomaly and
      did not succumb to the effects of the toxicant. Another colony was not eliminated
      because of invasion of the baiting system by ants. Ants, principally Iridomyrmex
      purpureus (F. Smith) group and Papyrius nitidus (Mayr) group, occurred commonly
      in the stations during the experiment. Microcerotermes sp. was found in five of
      the C. acinaciformis mounds, after colony elimination. Inspections of small
      sections of mounds and wooden dowels inserted into mounds were reliable methods
      for monitoring colony health.

PMID- 14977123
TI  - Exploitation of home range and spatial distribution of resources in German
      cockroaches (Dictyoptera: Blattellidae).
AB  - We analyzed the expression of edge following behavior in German cockroaches,
      Blattella germanica (L.). Structure of the environment and spatial distribution
      of resources modified both expression of locomotory behavior of cockroaches and
      its distribution between the edge and the central area of an experimental arena.
      When they are in a familiar environment, German cockroaches are definitely not
      edge followers and they exploit similarly the different parts of the accessible
      surface of their home range. Cockroaches placed in a new environment tended to
      follow edges more than undisturbed insects. This modification could be
      assimilated to a response to stressful conditions.

PMID- 14977124
TI  - Geographic variation in susceptibility of Chilo suppressalis (Lepidoptera:
      Pyralidae) to Bacillus thuringiensis toxins in China.
AB  - Geographic variation in the susceptibility of the striped stem borer, Chilo
      suppressalis (Walker) (Lepidoptera: Pyralidae), in China to Bacillus
      thuringiensis (Bt) insecticidal crystal proteins Cry1Ac and Cry1Ab was studied to
      establish baseline information for comparing the future response of populations
      with increased exposure to Bt products. Rice is the major host of C.
      suppressalis, and Bt rice ma) be released in China in the near future. Twelve
      populations of the pest were collected from the major rice-growing regions of
      China. LC50 estimates were determined for all populations for Cry1Ac and for
      eight populations for Cry1Ab. The bioassay results indicated that the range of
      LC50 in neonate larvae to Cry1Ac and Cry1Ab was from approximately 15 to
      approximately 157 mg (AI)/L and approximately 2 to approximately 34 mg (AI)/L,
      respectively. LC50 values were lower for Cry1Ab than for Cry1Ac, and there was a
      significant positive correlation between the two toxins tested.

PMID- 14977125
TI  - Regional and temporal variation in susceptibility to lambda-cyhalothrin in onion
      thrips, Thrips tabaci (Thysanoptera: Thripidae), in onion fields in New York.
AB  - Populations of onion thrips, Thrips tabaci Lindeman, from commercial onion fields
      in New York were evaluated for their susceptibility to the commonly used
      pyrethroid, lambda-cyhalothrin (Warrior T), using a novel system called the
      Thrips Insecticide Bioassay System (TIBS). To use TIBS, thrips are collected
      directly from the plant into an insecticide-treated 0.5-ml microcentrifuge tube
      that has a flexible plastic cap with a small well into which 0.08 ml of a 10%
      sugar-water solution with food colorant is deposited. The solution is sealed into
      the well with a small piece of stretched parafilm through which the thrips can
      feed on the solution. Thrips mortality is assessed after 24 h with the help of a
      dissecting stereoscope. In 2001, onion thrips populations were collected from 16
      different sites and resistance ratios were >1,000 in five populations. Percent
      mortality at 100 ppm, a recommended field rate, varied from 9 to 100%, indicating
      high levels of variation in susceptibility. Particular instances of resistance
      appeared to be the result of practices within an individual field rather than a
      regional phenomenon. In 2002, we also observed large differences in onion thrips
      susceptibility, not only between individual fields but also between thrips
      collected in a single field at mid season and late season, again suggesting that
      insecticide-use practices within an individual field caused differences in
      susceptibility. Additional tests indicated no differences in susceptibility
      between adult and larval onion thrips populations and only relatively minor
      differences between populations collected from different parts of the same field.
      Using TIBS, several populations of onion thrips with different susceptibilities
      to lambda-cyhalothrin were identified and then subjected to lambda-cyhalothrin
      treated onion plants. There was a highly significant positive relationship
      between percent mortality of thrips from TIBS and percent mortality from the
      treated onion plants, indicating that results from TIBS could be used to predict
      spray performance. These data suggest that use of TIBS for evaluating
      susceptibility to particular insecticides could be instrumental for developing a
      resistance management strategy for onion thrips.

PMID- 14977126
TI  - Biochemical monitoring of acetylcholinesterase sensitivity to organophosphorus
      insecticides in glassy-winged sharpshooter Homalodisca coagulata Say (Homoptera:
      Cicadellidae) and smoke-tree sharpshooter H. lacerta Fowler.
AB  - The glassy-winged sharpshooter Homalodisca coagulata Say (Homoptera:
      Cicadellidae) is a new pest to California agriculture. It is the principal vector
      of several plant pathogenic diseases, particularly Pierce's Disease in
      grapevines, and oleander leaf scorch. A microplate-based assay is described that
      measures the sensitivity of acetylcholinesterase (AChE) activity to inhibition by
      organophosphorus (OP) insecticides in this important pest. The technique provides
      users with an accurate measure of the efficacy of OP binding to this target site,
      and is a valuable tool for monitoring field populations of the insect to
      determine whether the use of OP insecticides has selected for resistant
      individuals. The technique will also measure AChE sensitivity in the smoke-tree
      sharpshooter, H. lacerta Fowler. This species is native to California and is
      regarded only as a minor pest. Both inhibition and kinetic measurements for the
      AChE enzymes in these sharpshooters demonstrate the close phylogenetic
      relationships between the two species.

PMID- 14977127
TI  - Characterization of general esterases from methyl parathion-resistant and 
      susceptible populations of western corn rootworm (Coleoptera: Chrysomelidae).
AB  - A consistent correlation between elevated esterase activity and methyl parathion
      resistance among Nebraska western corn rootworm, Diabrotica virgifera virgifera
      LeConte, populations has previously been documented. Characterization of general
      esterase activity using naphtholic esters as model substrates indicated that
      differences between resistant and susceptible strains could be maximized by
      optimizing assay conditions. The optimal conditions identified here were similar
      to those reported for other insect species. The majority of general esterase
      activity was found in the cytosolic fractions of resistant populations, whereas
      the activity was more evenly distributed between cytosolic and
      mitochondrial/nuclear fractions in the susceptible population. General esterase
      activity was predominately located in the adult thorax and abdomen. Although
      there were significant differences in general esterase activities between
      resistant and susceptible populations, the differences exhibited in single beetle
      activity assays did not provide sufficient discrimination to identify resistant
      individuals. In contrast, single larva activity assays provided greater
      discrimination and could be considered as an alternative to traditional bioassay
      techniques.

PMID- 14977128
TI  - Comparison of bioassay techniques for determining baseline susceptibilities to
      imidacloprid for green apple aphid (Homoptera: Aphididae).
AB  - The susceptibility of a clone of green apple aphid, Aphis pomi (De Geer), to the
      neonicotinyl insecticide imidacloprid was determined by direct and indirect
      bioassay techniques. Aphid numbers were assessed on potted apple seedlings
      treated with various concentrations of imidacloprid, adults were dipped in test
      solutions as per the Food and Agriculture Organization protocol, or nymphs and
      adults were reared on treated apple leaf disks. Effective concentrations required
      to kill half of the test population (EC50) varied depending on the bioassay
      technique, ranging from as low as 0.064 ppm for first instars reared for 3 d on
      treated leaf disks to 1.79 ppm for adult apterae dipped in solutions of
      imidacloprid and held for 24 h on clean leaf disks. When imidacloprid was
      directly applied to aphids, mortality continued to increase over 3 d, but the
      difference was not statistically significant between day 2 (1.36 ppm) and day 3
      (1.19 ppm). Toxicity of neonicotinyls to aphids is expressed rather slowly and
      primarily after oral ingestion. The effect of imidacloprid on reproduction of
      green apple aphid was also assessed for adult apterae reared on treated leaf
      disks. Contrary to previous reports, our results demonstrated that imidacloprid
      does not have a direct negative effect on the reproductive physiology of this
      species. Negative effects can mostly be attributed to the antifeedant activity of
      this compound and the protracted time to death. The results of this study
      contribute to a better understanding of the most suitable techniques for
      assessing aphid mortality after exposure to these new insecticides and provides a
      baseline susceptibility to imidacloprid for green apple aphid.

PMID- 14977129
TI  - Economics versus alleles: balancing integrated pest management and insect
      resistance management for rotation-resistant western corn rootworm (Coleoptera:
      Chrysomelidae).
AB  - Western corn rootworm, Diabrotica virgifera virgifera LeConte, has overcome crop
      rotation in several areas of the central United States. We expanded a simple
      model of adult behavior and population genetics to explain how rotation
      resistance may have developed and to study ways to manage the western corn
      rootworm in a landscape of corn, soybean, and winter wheat where evolution of
      resistance may occur. We modeled six alternative management strategies over a 15
      yr time horizon, as well as a strategy involving a 2-yr rotation of corn and
      soybean in 85% of the landscape, to investigate their effectiveness from both a
      biological and economic perspective. Generally, resistance to crop rotation
      evolves in fewer than 15 yr, and the rate of evolution increases as the level of
      rotated landscape (selection pressure) increases. When resistance is recessive,
      all six alternative strategies were effective at preventing evolution of rotation
      resistance. The two most successful strategies were the use of transgenic rotated
      corn in a 2-yr rotation and a 3-yr rotation of corn, soybean, and wheat with
      unattractive wheat (for oviposition) preceding corn. Results were most sensitive
      to increases in the initial allele frequency and modifications of the density
      dependent survival function. Economically, three alternative strategies were
      robust solutions to the problem, if technology fees were not too high. Repellant
      soybean, attractive rotated corn, and transgenic rotated corn, all in 2-yr
      rotations, were economically valuable approaches. However, even the currently
      common 2-yr rotation was economical when resistance was recessive and the actual
      costs of resistance would not be paid until far in the future.

PMID- 14977130
TI  - Mechanisms and diversity of resistance to insect pests in wild relatives of
      groundnut.
AB  - The levels of resistance to insect pests in cultivated groundnut (Arachis
      hypogaea) germplasm are quite low, and therefore, we screened 30 accessions of
      Arachis spp. and 12 derived lines for resistance to insect pests under field and
      greenhouse conditions. Accessions belonging to Arachis cardenasii, Arachis
      duranensis, Arachis kempff-mercadoi, Arachis monticola, Arachis stenosperma,
      Arachis paraguariensis, Arachis pusilla, and Arachis triseminata showed multiple
      resistance to the leaf miner Aproaerema modicella, Helicoverpa armigera, Empoasca
      kerri, and to rust, Puccnia arachidis Speg., and late leaf spot, Cercosporidium
      personatum (Berk. et Curt.). Arachis cardenasii (ICG 8216), Arachis ipaensis (ICG
      8206), A. paraguariensis (ICG 8130), and Arachis appressipila (ICG 8946) showed
      resistance to leaf feeding and antibiosis to Spodoptera litura under no-choice
      conditions. Six lines, derived from wild relatives, showed resistance to H.
      armigera and S. litura, and/or leaf miner. Plant morphological characteristics
      such as main stem thickness, hypanthium length, leaflet shape and length, leaf
      hairiness, standard petal length and petal markings, basal leaflet width, main
      stem thickness and hairiness, stipule adnation length and width, and peg length
      showed significant correlation and/or regression coefficients with damage by H.
      armigera, S. litura, and leafhoppers, and these traits can possibly be used as
      markers to select for resistance to these insect pests. Principal component
      analysis placed the Arachis spp. accessions into five groups, and these
      differences can be exploited to diversify resistance to the target insect pests
      in groundnut.

PMID- 14977131
TI  - Comparison of tall fescue (Cyperales: Gramineae) to other cool-season turfgrasses
      for tolerance to European chafer (Coleoptera: Scarabaeidae).
AB  - Three cultivars of tall fescue, Festuca arundinacea Schreb., were compared with
      three cultivars each of fine fescue (Festuca spp.), Kentucky bluegrass (Poa
      pratensis L.), and perennial ryegrass (Lolium perenne L.) to evaluate tolerance
      to root-feeding by European chafer grubs, Rhizotrogus majalis (Razoumowsky).
      Potted turfgrasses were infested with initial densities equivalent to 33 or 66
      grubs per 0.1 m2 on 19 August 2000. More grubs were added in late September and
      October, bringing the total to 66 or 143 grubs per 0.1 m2. Plant growth, root
      loss, weight gain, and survival of grubs were measured. The experiment was
      repeated in fall of 2001 with an initial density of 66 grubs per 0.1 m2. The
      proportion of root mass lost as a result of grub feeding was a function of turf
      species, root growth, grub survival, and grub growth during the test. Grubs
      gained the most weight and consumed the most roots when feeding on fine fescue.
      Fine fescue suffered the greatest percentage of root loss in 2000, despite having
      the most rapid root growth and largest mass in control pots. Cultivars of tall
      fescue appeared to be the most tolerant of grub feeding, having the smallest
      reduction in root mass in both years. Data from fine fescue, Kentucky bluegrass,
      and perennial ryegrass cultivars were not as consistent as tall fescue, because
      for some cultivars root growth and grub survival were different between years. We
      also found that grubs increased in mass by 20% when the mass of available roots
      was doubled.

PMID- 14977132
TI  - Cyanogenic potential in cassava and its influence on a generalist insect
      herbivore Cyrtomenus bergi (Hemiptera: Cydnidae).
AB  - The hypothesis that cyanogenic potential in cassava is a defense mechanism
      against arthropod pests is one of the crucial questions relevant to current
      efforts to reduce or eliminate cyanogenic potential (CNP) in cassava. The
      generalist arthropod Cyrtomenus bergi, which attacks cassava roots, was used in a
      bioassay relating oviposition and survival to CNP, concentration of nonglycosidic
      cyanogens, and linamarase (beta-glycosidase) activity in twelve selfed cassava
      siblings and their parental clone, which has segregated for different levels of
      cyanogenesis. Electron microscopic evaluation revealed an intracellular pathway
      of the stylet of C. bergi in the cassava root tissue to rupture cell walls. This
      feeding behavior causes cyanogenesis and increased linamarin content in the
      hemolymph of C. bergi while feeding on a cyanogenic diet. This diet resulted in a
      significant reduction in oviposition, especially at levels of CNP above 150 ppm
      (expressed as hydrogen cyanide) on fresh weight basis (or 400 ppm on dry weight
      basis) in cassava roots. An exponential decline in oviposition was observed with
      increasing levels of CNP, beginning 12 d after exposure to the cyanogenic diet.
      Cyanogenic potential and dry matter content showed a positive effect on survival.
      No relationship was found between concentrations of nonglycosidic cyanogens or
      linamarase activity in the cassava root and either oviposition or survival.
      According to our results, there is a significant difference between potentially
      noncyanogen and high cyanogen clones, but there may not be a significant
      difference between potentially noncyanogen and low cyanogen clones. Consequently,
      more frequent outbreaks or higher levels of damage might not be anticipated in
      potentially noncyanogen cassava clones than that anticipated in low cyanogenic
      clones. The negative effect of cyanogenesis on oviposition concurrent with a
      positive effect on survival of this pest is most likely the result of a
      physiological trade-off between survival and oviposition. The question of whether
      ovipositional rates could be recovered after a long-term exposure to cyanide
      remains unanswered.

PMID- 14977133
TI  - In field damage of high and low cyanogenic cassava due to a generalist insect
      herbivore Cyrtomenus bergi (Hemiptera: Cydnidae).
AB  - The hypothesis that cyanogenic potential in cassava roots deters polyphagous
      insects in the field is relevant to current efforts to reduce or eliminate the
      cyanogenic potential in cassava. To test this hypothesis, experiments were
      conducted in the field under natural selection pressure of the polyphagous root
      feeder Cyrtomenus bergi Froeschner (Hemiptera: Cydnidae). A number of cassava
      varieties (33) as well as 13 cassava siblings and their parental clone, each
      representing a determined level of cyanogenic potential (CNP), were scored for
      damage caused by C. bergi and related to CNP and nonglycosidic cyanogens,
      measured as hydrogen cyanide. Additionally, 161 low-CNP varieties (< 50 ppm
      hydrogen cyanide, fresh weight) from the cassava germplasm core collection at
      Centro Internacional de Agricultura Tropical (CIAT) were screened for
      resistance/tolerance to C. bergi. Low root damage scores were registered at all
      levels of CNP. Nevertheless, CNP and yield (or root size) partly explained the
      damage in cassava siblings (r2 = 0.82) and different cassava varieties (r2 =
      0.42), but only when mean values of damage scores were used. This relation was
      only significant in one of two crop cycles. A logistic model describes the
      underlying negative relation between CNP and damage. An exponential model
      describes the underlying negative relation between root size and damage. Damage,
      caused by C. bergi feeding, released nonglycosidic cyanogens, and an exponential
      model fits the underlying positive relation. Fifteen low-CNP clones were selected
      for potential resistance/tolerance against C. bergi.

PMID- 14977134
TI  - Characterization of greenbug (Homoptera: Aphididae) resistance in synthetic
      hexaploid wheats.
AB  - Twelve greenbug (Schizaphis graminum (Rondani)) biotype E-resistant synthetic
      hexaploid wheats synthesized by crossing Triticum dicoccum Schrank. and Aegilops
      tauschii (Coss.) Schmal. were evaluated for the three known insect resistance
      categories, including antibiosis, anti-xenosis, and tolerance. Different methods
      were evaluated for calculating antibiosis and tolerance. Calculating intrinsic
      rate of population increase and measuring leaf chlorophyll content with a SPAD
      chlorophyll meter proved to be time- and labor-efficient for antibiosis and
      tolerance determination, respectively. The resistance in all synthetic hexaploids
      proved to be the result of a combination of antibiosis, antixenosis, and
      tolerance, which makes them valuable sources of greenbug resistance. To assist
      plant breeders in selecting the best germplasm for greenbug resistance, a plant
      resistance index was created that revealed differences among the synthetic
      hexaploid wheats.

PMID- 14977135
TI  - Resistance to the Mexican rice borer (Lepidoptera: Crambidae) among Louisiana and
      Texas sugarcane cultivars.
AB  - A 2-yr study to evaluate Louisiana and Texas sugarcane, Saccharum spp., cultivars
      for resistance to the Mexican rice borer, Eoreuma loftini (Dyar) was conducted in
      two locations in Texas, chosen for having different infestation levels. Criteria
      for assessment of resistance included percentage of bored internodes and adult
      emergence holes, the latter used to determine the relative impact of each
      cultivar on the potential areawide buildup or reduction of adult E. loftini
      populations. A recently released cultivar, HoCP 85-845, seemed to lose a portion
      of its resistance under heavy E. loftini infestation pressure, suggesting its
      value only in moderate-to-low infestation conditions. Cultivar CP 70-321 was the
      most resistant. Results indicated that cultivar LCP 85-384 was significantly (P <
      0.05) more susceptible than NCo 310, traditionally the most susceptible cultivar
      commercially produced in Texas. In 2001, LCP 85-384, which now represents 85% of
      the production area in Louisiana, had the greatest moth production per hectare
      (17,052 +/- 3,956) under the lower infestation pressure, significantly (P < 0.05)
      higher than HoCP 85-845 (3,038 +/- 2,353). In a portion of the test at the high
      infestation location, high levels of sodium and magnesium salt stress (15-30-cm
      soil depth) were associated with higher E. loftini damage in all cultivars except
      HoCP 91-555 and CP 70-321.

PMID- 14977136
TI  - Do rice hybrids have heterosis for insect resistance? A study with Nilaparvata
      lugens (Hemiptera: Delphacidae) and Marasmia patnalis (Lepidoptera: Pyralidae).
AB  - Antibiosis-based resistance to two insect pests of rice, Nilaparvata lugens
      (Stal) (Hemiptera: Delphacidae) and Marasmia patnalis Bradley (Lepidoptera:
      Pyralidae), was compared in 11 F1 hybrids and their parental lines. Our objective
      was to determine whether hybrids show heterosis (hybrid vigor) for insect
      resistance or susceptibility. Heterosis is defined as the amount by which a
      hybrid exceeds its midparent value or its better parent. Overall, we did not find
      evidence of heterosis or heterobeltiosis (a type of heterosis in which a hybrid
      exceeds its better parent) for antibiosis-based resistance or susceptibility to
      either of the insects. One hybrid, IR64616H, seemed more resistant to M. patnalis
      than its better parent but none of the other hybrids showed heterobeltiosis for
      resistance or susceptibility to either insect. Three hybrids had resistance to N.
      lugens that exceeded their midparent value, possibly due to dominant resistance
      in one of the parents. The increased frequency and severity of insect outbreaks
      on hybrid rice that have been reported in China may be attributable to factors
      other than diminished antibiosis in hybrids, such as greater attractiveness of
      hybrids to migrating or dispersing insects or differences in agronomic practices
      applied to hybrids and inbred rice cultivars.

PMID- 14977137
TI  - Chinch bug-resistant buffalograss: an investigation of tolerance, antixenosis,
      and antibiosis.
AB  - Choice and no-choice studies were conducted to determine the categories
      (antibiosis, antixenosis, and tolerance) of resistance of four buffalograsses
      (NE91-118, 'Bonnie Brae', 'Cody', and 'Tatanka') previously identified as
      resistant to the western chinch bug, Blissus occiduus Barber. Antibiosis studies
      found no significant differences in western chinch bug fecundity, nymphal
      development, or survival among the resistant and susceptible buffalograsses.
      Tolerance studies indicated that NE91-118, Cody, and Tatanka exhibited moderate
      to-high levels of tolerance based on western chinch bug damage ratings and plant
      height, whereas Bonnie Brae exhibited moderate-to-low levels of tolerance. Choice
      studies indicated the presence of antixenosis in NE91-118, whereas Cody and
      Tatanka showed little or no antixenosis. Scanning electron microscopy was used to
      disclose morphological differences between NE91-118 (resistant) and '378'
      (susceptible). The epicuticular wax structures and trichome densities were
      similar between 378 and NE91-118, suggesting that morphological structures do not
      contribute to NE91-118 antixenosis.

PMID- 14977138
TI  - Use of commercial freezers to control cowpea weevil, Callosobruchus maculatus
      (Coleoptera: Bruchidae), in organic garbanzo beans.
AB  - One California processor of organic garbanzo beans (Cicer arietinum L.), unable
      to use chemical fumigants, relies on 30-d storage at -18 degrees C to disinfest
      product of the cowpea weevil, Callosobruchus maculatus (F). To determine whether
      the storage period may be shortened, the most cold-tolerant life stage of the
      cowpea weevil was identified. Laboratory studies showed that the egg stage was
      most tolerant to -18 degrees C and that adults were most susceptible. To examine
      the efficacy of cold storage disinfestation, bags of black-eyed peas, Vigna
      unguiculata (L.) Walp., infested with cowpea weevil eggs were buried within
      garbanzo bean bins placed in a commercial cold storage facility kept at
      approximately -18 degrees C and removed after 7, 14, and 21 d. Survival was
      highest in eggs located at the center of the bins and coincided with the slowest
      cooling rate. Although temperatures within the bins did not reach -18 degrees C
      until after 14-19 d, egg mortality was estimated to be >98% after just 7 d of
      exposure. Complete mortality of eggs occurred after 14 d of cold storage. A 2-wk
      treatment regimen may be sufficient for control of cowpea weevil in organic
      legumes.

PMID- 14977139
TI  - Stored-product insects associated with a retail pet store chain in Kansas.
AB  - The types and numbers of insect species associated with eight Kansas retail
      stores belonging to a pet store chain were surveyed during February to August
      2001. Insects were monitored at 1-3-wk intervals using food- and pheromone-baited
      pitfall traps for beetles and pheromone-baited sticky traps for moths. Thirty
      traps of each type were placed within a store. Thirty insect species belonging to
      20 families in four orders were recorded from the eight stores. The weevils,
      Sitophilus spp.; Indianmeal moth, Plodia interpunctella (Hubner); and merchant
      grain beetle, Oryzaephilus mercator (Fauvel), were the most common and abundant
      species in all stores, whereas the red-legged ham beetle, Necrobia rufipes
      (Degeer), and red flour beetle, Tribolium castaneum (Herbst), were abundant only
      in one store. The numbers of each insect species captured varied from store to
      store. In each of the stores, a total of 12-19 stored-product species were
      captured in traps, and seven of the eight stores had relatively high species
      diversity. With the exception of one store, the different types of insect species
      found among the remaining seven stores were essentially similar. The mean density
      of insects in infested bulk-stored and bagged pet food products removed from a
      store ranged from 65 to 656 adults/kg. The types and numbers of insect species
      captured in traps indicated that infestations were well established in the
      surveyed stores. Early detection and management of these infestations is critical
      for maintaining quality and integrity of food products sold in the pet stores.

PMID- 14977140
TI  - Knockdown and mortality of adults of eight species of stored-product beetles
      exposed to four surfaces treated with spinosad.
AB  - Contact toxicity of a commercial bacterial fermentation insecticide, spinosad, to
      adults of eight stored-product beetles was evaluated on four different surfaces.
      Aqueous spinosad suspension was sprayed with an airbrush to 30.5-cm2 surfaces of
      concrete, galvanized steel, unwaxed floor tile, or waxed floor tile to obtain
      deposits of 0.05 or 0.1 mg (AI)/cm2. Control surfaces were sprayed with distilled
      water. Approximately 24 h after distilled water or spinosad application, 30 adult
      beetles were confined, by species, to each untreated and spinosad-treated
      surface. Insects on surfaces were exposed for 24 h to assess knockdown at 25 +/-
      1 degree C and 50 +/- 10% RH, and then were held on food for an additional 24 h
      to assess mortality. Knockdown and mortality of each insect species on all four
      surfaces were significantly greater on spinosad-treated surfaces than on
      distilled water-treated surfaces. Knockdown and mortality of all species on all
      surfaces was similar at the two spinosad deposit levels. Except for Tribolium
      spp., mortality of all other species exposed to spinosad was 99-100%. Tribolium
      spp. were highly susceptible to spinosad on concrete (98-100% mortality);
      however, on unwaxed floor tile, steel, and waxed floor tile recovery on food
      after knockdown resulted in only 72-92% mortality. Our results suggest that
      spinosad has excellent contact activity against adults of stored-product insects,
      especially on concrete, and has potential for use as a general surface, spot, or
      crack/crevice spray to control insects in empty bins, warehouses, food-processing
      facilities, and retail stores.

PMID- 14977141
TI  - Dechlorination of chlorinated phenols by zero valent zinc.
AB  - Reductive dechlorination of chlorophenols (Pentachlorophenol, three
      tetrachlorophenols (TeCPs), six trichlorophenols (TCPs)) with zero valent zinc
      was examined through batch experiments. Zinc showed much higher reactivity
      towards PCP than iron and amended iron indicating that zero valent zinc can be a
      good candidate for reductive dechlorination of chlorinated phenols. Chlorophenols
      were sequentially dechlorinated and less chlorinated phenols were identified as
      reduction products. The mass balance was not complete, indicating that by
      products are important and/or that products being measured were lost by unknown
      pathways. The dechlorination rate of the chlorinated phenols usually followed the
      order: PCP > TeCPs > TCPs. Among the TeCP and TCP isomers, the reactivity was in
      the order of 2,3,4,5-TeCP > 2,3,4,6-TeCP > 2,3,5,6-TeCP and 2,3,4-TCP > 2,3,6-TCP
      > 2,3,5-TCP > 2,4,6-TCP > 2,4,5-TCP > 3,4,5-TCP. The first order reaction rates
      varied by one order of magnitude or more, depending on the chlorines positions on
      a phenol ring. A regioselectivity was observed and daughter compound
      distributions could be rationalized by a mechanism in which radical intermediates
      were more stabilized by chlorine and hydroxyl groups than by hydrogen; positions
      alpha to the radical were found to be the most important in stabilization,
      followed by beta-positions.

PMID- 14977142
TI  - Volatile fatty acids as malodorous compounds in wool scouring water and lanolin.
      Origin and characterisation.
AB  - Volatile fatty acids (C2-C7) analysis in wool scouring water and lanolin is
      presented. These substances are of major interest as malodorous compounds in
      urban and industrial wastewaters. In this work, they have been analysed in wool
      scouring water by headspace solid-phase microextraction followed by gas
      chromatography negative chemical ionisation mass spectrometry. Most of the
      volatile fatty acids have been identified at microg g(-1) levels. In addition,
      since lanolin is a major impurity of raw wool, volatile fatty acid patterns of
      wool scouring water and lanolin have been compared in order to establish the
      origin of these compounds in the wastewater. Finally, the efficiency of the
      deodorization step, mandatory to obtain commercial lanolin, has been assessed
      taking into account the decrease in volatile fatty acid content from the raw wool
      to the lanolin.

PMID- 14977143
TI  - Kinetics of glucose fermentation by a mixed culture in the presence of linoleic,
      oleic, and stearic acid.
AB  - The effects of long chain fatty acids (LCFAs) on glucose degradation were
      examined at 21 degrees C. A competitive inhibition model was used to determine
      the kinetics of glucose degradation. Half velocity constants (Ks) were a function
      of LCFA concentration only at 100, 300 and 500 mg l(-1). The inhibitor constants
      (KI) for individual and mixed LCFAs were statistically the same. Glucose
      degradation rates for cultures receiving saturated (stearic acid (SA)) and
      monounsaturated (oleic acid (OA)) LCFAs were statistically the same but
      statistically different when compared to cultures fed with a polyunsaturated LCFA
      (linoleic acid (LA)). Individual and mixed LCFAs inhibited glucose degradation at
      threshold levels of 300 and 500 mg l(-1), respectively.

PMID- 14977144
TI  - An equation characterizing multi-heavy-metal sorption onto bentonite, forest soil
      and spruce bark.
AB  - An empirical equation was developed to quantitatively describe heavy metal
      sorption in ternary systems of lead (Pb), copper (Cu) and cadmium (Cd). The three
      sorbants investigated were bentonite, forest soil and spruce bark. This multi
      sorption equation is based on three assumptions: the relationship between
      sorption and initial heavy metal concentration fits a power curve; the presence
      of one heavy metal proportionately reduces the sorption curve of another heavy
      metal; and the competition between two heavy metals is independent of the
      presence of other heavy metals. The multi-sorption equation modeled sorption in
      ternary systems to a regression fit greater than 0.96. The data required for the
      equation were generated from a technically straightforward and quick laboratory
      program involving batch adsorption tests.

PMID- 14977145
TI  - Sonochemical degradation of phenolic pollutants in aqueous solutions.
AB  - The sonochemical degradation of phenol, 2-chlorophenol and 3,4-dichlorophenol in
      aqueous solutions as a function of several operating conditions has been
      investigated. Experiments were performed at initial substrate concentrations of
      0.1, 0.5 and 1 g l(-1), liquid phase volumes of 0.05, 0.07 and 0.08 l, electric
      power outputs of 125, 187.5 and 250 W, liquid bulk temperatures of 20, 35, 50 and
      70 degrees C and an ultrasound frequency of 20 kHz. Substrate concentration was
      determined as a function of time by means of high performance liquid
      chromatography. At the conditions under consideration, the rate of degradation
      follows first order kinetics with respect to the substrate concentration and
      increases with increasing electric power and decreasing liquid volume. The
      relative reactivity appears to decrease in the order: 2-chlorophenol > 3,4
      dichlorophenol > phenol. Measurements of liquid phase total organic carbon
      content showed that degradation by-products are more recalcitrant than the
      original substrate. The rate of 2-chlorophenol degradation was also found to
      decrease with decreasing liquid bulk temperature and increasing initial
      concentration. Addition of t-butanol as a hydroxyl radical scavenger only
      partially inhibited degradation, thus implying that degradation is likely to
      proceed via both radical-induced and thermal reactions. Addition of Fe2+ ions at
      concentrations as low as about 0.2 x 10(3) g l(-1) resulted in increased
      degradation rates; this is attributed to iron being capable of readily
      decomposing hydrogen peroxide (generated by water sonolysis) in a Fenton-like
      process to form hydroxyl radicals as well as being an effective oxidation
      catalyst. The implications of the use of ultrasound in wastewater treatment are
      also discussed.

PMID- 14977146
TI  - Biosorption of cadmium (II) and copper (II) by pretreated biomass of marine alga
      Gracilaria fisheri.
AB  - The cadmium (II) and copper (II) adsorption properties of chemically pretreated
      biomass of red marine alga Gracilaria fisheri were investigated. Batch
      equilibrium experiments showed that the maximum adsorption capacity values of the
      pretreated biomass for cadmium and copper were 0.63 and 0.72 mmol g(-1),
      respectively. The equilibrium data fitted well to the Langmuir isotherm model.
      The adsorption capacity increased as pH increased and reached a plateau at pH
      4.0. The cadmium and copper uptake rates were rapid with 90% of the biosorption
      completed within 30 minutes. The presence of light metal ions (Na+, K+, Mg2+ and
      Ca2+) in solution had an insignificant effect on cadmium and copper sorption
      capacity. These findings indicate a positive potential for the biosorbent
      development with effective heavy metal removal capacity in the presence of light
      metal ions in waste streams by using the biomass of plentifully available red
      marine algae.

PMID- 14977147
TI  - Remediation of coal mining wastewaters using chitosan microspheres.
AB  - This study aimed to evaluate the potential use of chitosan and
      chitosan/poly(vinylalcohol) microspheres incorporating with tetrasulphonated
      copper (II) phthalocyanine (CTS/PVA/TCP) in the remediation of coal mining
      wastewaters. The process was monitored by toxicity tests both before and after
      adsorption treatments with chitosan and microspheres. Physicochemical parameters,
      including pH and trace-metal concentration, as well as bioindicators of water
      pollution were used to that end. Wastewater samples colleted from drainage of
      underground coal mines, decantation pools, and contaminated rivers were
      scrutinized. Acute toxicity tests were performed using the Brine Shrimp Test
      (BST) in order to evaluate the remediation efficiency of different treatments.
      The results showed that the pH of treated wastewater samples were improved to
      values close to neutrality. Chitosan treatments were also effective in removing
      trace-metals. Pre-treatment with chitosan followed by microsphere treatment
      (CTS/PVA/TCP) was more effective in decreasing toxicity than the treatment using
      only chitosan. This was probably due to the elimination of pollutants other than
      trace-metals. Thus, the use of chitosan and microspheres is an adequate
      alternative towards remediation of water pollution from coal mining.

PMID- 14977148
TI  - Distributions of iron, manganese, copper and zinc in various composts and amended
      soils.
AB  - A detailed observation was conducted on Fe, Mn, Cu and Zn in the composts derived
      from seafood processing by-product, garbage, swine manure and sewage sludge,
      respectively, as well as in amended farmlands. All elements were at lower levels
      of total contents but a higher percentage of water-soluble and exchangeable forms
      in composted seafood processing by-product and composted garbage than in
      composted swine manure and composted sewage sludge. Total contents increased in
      the order: composted seafood processing by-product approximately composted
      garbage < composted swine manure < composted sewage sludge. The applications of
      composted seafood processing by-product and composted garbage have neither caused
      Fe, Mn, Cu and Zn accumulation nor changed their distribution in soils; while the
      application of composted swine manure has largely increased Cu and Zn contents in
      soils, mainly in organic matter-bound form, and that of composted sewage sludge
      increased Mn, Cu and Zn in soils mainly in carbonate-bond and Fe-Mn oxides-bound
      ones. Fe is an exception, its total contents in soils decreased with the
      applications of composts except for composted garbage. Also, the rainfall and
      irrigation were another two main factors that affected available elements in
      soils.

PMID- 14977149
TI  - Validation tests of a new high uptake rate passive sampler for nitrogen dioxide
      measurements.
AB  - This study explains the main characteristics of a new passive sampler which is
      able to give reliable nitrogen dioxide measurements for short time sampling. The
      sampling rate was found to be on average 0.89 cm3 s(-1) for indoor sampling and
      1.00 cm3 s(-1) for outdoor sampling. The detection limit was evaluated at 11
      microg m(-3) for a one-hour measurement. In field conditions, the passive sampler
      measurements were in agreement with those of the chemiluminescent NOx monitors.
      Measurement uncertainties were estimated at 34% and 38% for laboratory tests in
      conditions corresponding respectively to indoor and outdoor measurements and were
      evaluated at 28 to 37% depending on the nitrogen dioxide concentration for field
      experiments. The effects of various factors on the passive sampler were
      determined in an exposure chamber. The sampling rate of the retained sampler
      version was not significantly influenced by wind speeds superior to 0.3 m s(-1).
      A decrease of the uptake rate is observed for high nitrogen dioxide doses. The
      sampling rate increases linearly with temperature (2% per degree C). The relative
      humidity has only a weak effect.

PMID- 14977150
TI  - Biological treatment of a contaminated gaseous emission containing
      monochlorobenzene.
AB  - This study presents the operation of a biotrickling filter when treating a
      monochlorobenzene (MCB) contaminated gaseous emission. Treatment dynamics were
      characterised by exposing the reactor to various MCB Organic Loads (OL). The use
      of different growth support materials, namely limestone, sand, ceramic and PVC
      pall-rings, was investigated. Limestone led to dogging of the reactor due to the
      accumulation of surface precipitates, but PVC pall-rings allowed for a uniform
      biofilm growth. The biotrickling filter presented maximum removal efficiency (RE,
      95%) under OL regimes of 10 g m(-3)-reactor h(-1). Treatment inhibition was
      observed when the reactor was exposed to OL of 45 g m(-3)-reactor h(-1), with RE
      reaching a minimum value (8%) and elimination capacity of 8 g m(-3)-reactor h(
      1). The first half of the reactor height was the predominant section for MCB
      biodegradation and increasing the mineral medium recirculation rate was
      beneficial for the overall treatment.

PMID- 14977151
TI  - Assessment of anaerobic sewage sludge quality for agricultural application after
      metal bioleaching.
AB  - The effects of metal bioleaching on nutrient solubilization, especially nitrogen
      and phosphorous, from anaerobically-digested sewage sludge were investigated in
      this work. The assessment of the sanitary quality of the anaerobic sludge after
      bioleaching was also carried out by enumerating indicator (total coliforms, fecal
      coliforms, and fecal streptococci) and total heterotrophic bacteria. The
      experiments of bioleaching were performed using indigenous sulphur-oxidizing
      bacteria (Thiobacillus spp.) as inoculum and samples of anaerobically-digested
      sludge. Nitrogen and phosphorous solubilization from sewage sludge was assessed
      by measuring, respectively, the concentration of Total Kjeldahl Nitrogen,
      ammonia, nitrate/nitrite, and soluble and total phosphorous before and after the
      bioleaching assays. At the end of the experiment, after 4 days of incubation
      (final pH of 1.4), the following metal solubilization yields were obtained: zinc,
      91%; nickel, 87%; copper, 79%; lead, 52%; and chromium, 42%. As a result of
      sludge acidification, the viable counts of selected indicator bacteria were
      decreased to below the detection limit (4 x 10(3) cfu 100 ml(-1)), followed by an
      increase in the mineral fraction of nitrogen (from 6 to 10%) and in the soluble
      fraction of phosphorous (from 15 to 30%). Although some loss of sludge nutrients
      can occur during solid-liquid separation following bioleaching, its beneficial
      effects as metal removal and reduction of pathogenic bacteria are sufficient to
      consider the potential of this treatment before sludge disposal onto agricultural
      fields.

PMID- 14977152
TI  - Treatment of domestic wastewater by subsurface flow constructed wetlands filled
      with gravel and tire chip media.
AB  - Subsurface flow constructed wetlands (SFCWs) are becoming increasingly common in
      on-site treatment of wastewater. Gravel is the most popular form of wetland fill
      medium, but tire chips provide more porosity, are less dense, and less expensive.
      This study determines the treatment efficiency of SFCWs filled with gravel or
      tire chip media to treat domestic wastewater. The influent and effluent of six
      SFCWs filled with tire chip medium and six SFCWs filled with gravel were
      monitored for 5 to 16 consecutive months. Parameters measured included pH,
      biochemical oxygen demand (BOD5), total and volatile suspended solids, NH4, P,
      and fecal and total coliforms. The only clear difference between medium types in
      wetland performance was for P. Soluble P in the effluent averaged 1.6 +/- 1.0 mg
      l(-1) in the tire chip-filled wetlands and 4.8 +/- 3.2 mg l(-1) in the gravel
      filled wetlands. Most likely, Fe from exposed wires in shredded steel-belted
      tires complexed with P to create an insoluble compound. Tire chips may be a
      better fill medium for SFCWs than gravel because of higher porosity, lower cost,
      and greater reduction of P in effluent.

PMID- 14977153
TI  - A novel control process of cyanobacterial bloom using cyanobacteriolytic bacteria
      immobilized in floating biodegradable plastic carriers.
AB  - A process using a floating carrier for immobilization of cyanobacteriolytic
      bacteria, B.cereus N-14, was proposed to realize an effective in situ control of
      natural floating cyanobacterial blooms. The critical concentrations of the
      cyanobacteriolytic substance and B.cereus N-14 cells required to exhibit
      cyanobacteriolytic activity were investigated. The results indicated the
      necessity of cell growth to produce sufficiently high amounts of the
      cyanobacteriolytic substance to exhibit its activity and also for conditions
      enabling good contact between high concentrations of the cyanobacteriolytic
      substance and cyanobacteria. Floating biodegradable plastics made of starch were
      applied as a carrier material to maintain close contact between the immobilized
      cyanobacteriolytic bacteria and floating cyanobacteria. The floating starch
      carriers could eliminate 99% of floating cyanobacteria in 4 d. Since B.cereus N
      14 could produce the cyanobacteriolytic substance under the presence of starch
      and some amino acids, the cyanobacteriolytic activity could be attributed to
      carbon source fed from starch carrier and amino acids eluted from lysed
      cyanobacteria. Therefore, the effect of using a floating starch-carrier was
      confirmed from both view points as a carrier for immobilization and a nutrient
      source to stimulate cyanobacteriolytic activity. The new concept to apply a
      floating carrier immobilizing useful microorganisms for intensive treatment of a
      nuisance floating target was demonstrated.

PMID- 14977154
TI  - Multiple sexual-partner behavior among sexually active US adolescent girls.
AB  - OBJECTIVE: To examine the relationship of multiple sexual-partners to other risk
      behaviors among adolescent girls. METHODS: Ninth- through 12th-grade sexually
      active girls (N=3288) who completed the 1999 national Youth Risk Behavior Survey
      were participants. Multivariate logistic regression was used to examine all
      significant independent relationships. RESULTS: Having one recent sexual-partner
      was associated with lack of condom use and being in 12th grade whereas having 2
      or more partners was associated with fighting, cigarette use, binge drinking, and
      African American ethnicity. CONCLUSIONS: A small but important subset of
      adolescent girls report having recent multiple sexual-partners. These girls are
      more likely to report other problem-prone health behaviors.

PMID- 14977155
TI  - The PHLAME firefighters' study: feasibility and findings.
AB  - OBJECTIVE: To assess efficacy of 2 worksite health promotion interventions.
      METHODS: Randomly assign 3 fire stations to (a) team-based curriculum, (b)
      individual counselor meetings, and (c) control. RESULTS: Both interventions were
      feasible and acceptable, and they resulted in significant reductions in LDL
      cholesterol. The team approach significantly increased coworker cohesion,
      personal exercise habits, and coworkers' healthy behaviors. The one-on-one
      strategy significantly increased dietary self-monitoring, decreased fat intake,
      and reduced depressed feelings. CONCLUSIONS: Although both interventions promoted
      healthy behaviors, specific outcomes differed and reflected their conceptual
      underpinnings. The team-based curriculum is innovative and may enlist influences
      not accessed with individual formats.

PMID- 14977156
TI  - Change in diet, physical activity, and body weight in female college freshman.
AB  - OBJECTIVE: To examine diet, physical activity, and body-weight changes associated
      with relocation from home to university. METHODS: Diet, fitness/physical
      activity, body-weight parameters and self-efficacy were assessed among 54
      freshman women upon college entry and 5 months later. RESULTS: Although caloric
      intake significantly decreased, a significant increase occurred in body-weight
      parameters that may be attributed to significant decreases in total physical
      activity. CONCLUSIONS: Interventions are needed aimed at increasing physical
      activity; improving diet quality related to consumption of vegetables, fruits,
      breads and pasta, and meats; and decreasing alcohol consumption.

PMID- 14977157
TI  - Condom use among low-income African American males attending an STD clinic.
AB  - OBJECTIVE: To evaluate condom-use attitudes and behaviors among low-income,
      primarily African American, male patients seeking care at an urban sexually
      transmitted disease (STD) clinic. METHODS: Via face-to-face interviews, 224 males
      completed a theory-based questionnaire regarding condom use. RESULTS: The results
      show that although respondents had obvious signs and symptoms of infection and
      that 65% were "repeaters" at the clinic, 66% of the sample reporting a main
      partner and 33% of those with other types of sexual partners were not
      motivationally ready to use condoms consistently. CONCLUSION: Based on their STD
      clinic attendance, these men obviously perceive themselves at risk for STDs, but
      appear to cope with this risk by choosing to engage in secondary rather than
      primary preventive behaviors.

PMID- 14977158
TI  - Using cognitive mapping to develop a community-based family intervention.
AB  - OBJECTIVE: To describe the development of a consumer-oriented intervention for
      increasing intake of fruits and vegetables (FVs) in families (n=265). METHOD: A
      cognitive-mapping approach was used to specify intervention performance
      objectives and a tailoring strategy. RESULTS: MDS and hierarchical cluster
      analysis indicated that FV perceptions are organized into 6 clusters arrayed
      along 3 dimensions. In combination with 3 general family-functioning measures, 11
      perceptions explained approximately 18% of the variance in parent FVI. K-means
      cluster analysis revealed 4 types of families. CONCLUSION: Cognitive mapping
      provides a systematic approach for including qualitative data in the design of
      tailored interventions.

PMID- 14977159
TI  - Changes in adolescent cigarette-brand preference, 1989 to 1996.
AB  - OBJECTIVE: To understand changes in cigarette-brand choice by adolescents in the
      context of demographic differences and advertising. METHODS: Data from 3
      nationally representative cross-sectional surveys of adolescents were analyzed.
      RESULTS: Marlboro, Camel, and Newport brand cigarettes accounted for over 80% of
      the cigarettes usually bought by adolescents in 1989, 1993, and 1996. Between
      1989 and 1996, Marlboro and Camel market shares changed little, whereas
      preference for Newport doubled among white and Hispanic adolescents. CONCLUSIONS:
      Brand preference among adolescents has been steadily concentrated among 3 brands.
      More attention may need to be focused on mentholated brands given the increase in
      Newport's market share.

PMID- 14977160
TI  - Tobacco use and cessation behavior among adolescents participating in organized
      sports.
AB  - OBJECTIVES: To examine the difference in tobacco use between adolescents who
      participate in organized sports and those who do not. METHODS: Using a cross
      sectional study design, this study uses data from a nationally representative
      sample of adolescents enrolled in public high schools in the United States.
      RESULTS: Those participating in organized sports were 25% less likely to be
      current cigarette smokers. However, smokeless tobacco use was found to be
      associated with participation in organized sports. CONCLUSIONS: Given the large
      proportion of students involved in organized sports, intervening through this
      venue to address tobacco use has the potential to reach significant numbers of
      adolescents.

PMID- 14977162
TI  - ViewPoint: human or interpersonal side of research.

PMID- 14977161
TI  - Comparative testing of 5 nicotine systems: initial use and preferences.
AB  - OBJECTIVE: To test initial reactions to 5 nicotine treatments (NRTs: 2 and 4 mg
      gum, inhaler, nasal spray, tablet) in a crossover study (n=41). METHODS: Subjects
      used each medication on arising (1/2 day) and resumed smoking each afternoon.
      Subjects rated (individually) and ranked (comparatively) treatments on use,
      reinforcement, withdrawal, craving, and preferences. RESULTS: Overall
      preferences: inhaler (49%), 4 mg gum (24%), 2 mg gum (10%), 2 mg tablet (10%),
      nasal spray (7%). Overall results were consistent with ratings and rankings of
      individual characteristics of drugs. CONCLUSION: Subjects had varied reactions to
      NRTs that may affect initiation of cessation.

PMID- 14977163
TI  - A two-part mixture model for longitudinal adverse event severity data.
AB  - We fit a mixed effects logistic regression model to longitudinal adverse event
      (AE) severity data (four-point ordered categorical response) to describe the dose
      AE severity response for an investigational drug. The distribution of the
      predicted interindividual random effects (Bayes predictions) was extremely
      bimodal. This extreme bimodality indicated that biased parameter estimates and
      poor predictive performance were likely. The distribution's primary mode was
      composed of patients that did not experience an AE. Moreover, the Bayes
      predictions of these non-AE patients were nearly degenerative, i.e., the
      predictions were nearly identical. To resolve this extreme bimodality we propose
      using a two-part mixture modeling approach. The first part models the incidence
      of AE's, and the second part models the severity grade given the patient had an
      AE. Unconditional probability predictions are calculated by mixing the incidence
      and severity model probability predictions. We also report results of simulation
      studies, which assess the predictive and statistical (bias and precision)
      performance of our approach.

PMID- 14977164
TI  - Volterra series in pharmacokinetics and pharmacodynamics.
AB  - Nonparametric black-box modeling has a long successful history of applications in
      pharmacokinetics (PK) (notably in deconvolution), but is rarely used in
      pharmacodynamics (PD). The main reason is associated with the fact that PK
      systems are often linear in respect to drug inputs, while the reverse is true for
      many PK/PD systems. In the PK/PD field existing non-parametric methods can deal
      with linear systems, but they cannot describe non-linear systems. Our purpose is
      to describe a novel implementation of a general nonparametric model which can
      represent non-linear systems, and in particular non-linear PK/PD systems, The
      model is based on a Volterra series, which is an integral series expansion of the
      response of a system in terms of its kernels and the inputs to the system. In PK
      we are familiar with the first term of the Volterra series, the convolution of
      the first kernel of the system (the so-called PK disposition function) with drug
      input rates. The main advantages of higher order Volterra representations is that
      they are general representations and can be used to describe and predict the
      response of an arbitrary (PK/ PD) system without any prior knowledge on the
      structure of the system. The main problem of the representation is that in a non
      parametric representation of the kernels the number of parameters to be estimated
      grows geometrically with the order of the kernel. We developed a method to
      estimate the kernels in a Volterra-series which overcomes this problem. The
      method (i) is fully non-parametric (the kernels are represented using
      multivariate splines), (ii) is maximum-likelihood based, (iii) is adaptive (the
      order of the series and the dimensionality of each kernel is selected by the
      method), and (iv) allows for non-equispaced observations (thus allowing a
      reduction of the number of parameters in the representation, and the analysis of,
      e.g., PK/PD observations). The method is based on an adaptation of Friedmans's
      Multivariate Adaptive Regression Spline method. Examples demonstrate the possible
      application of the approach to the analysis of different PK/PD systems.

PMID- 14977165
TI  - Estimation of Cmax and Tmax in populations after single and multiple drug
      administrations.
AB  - Following the oral administration of drugs, the plasma concentration generally
      reaches, in principle, a single, well-defined peak (Cmax) at the time of Tmax. A
      complication for the direct estimation of Cmax and Tmax is that measurements of
      concentrations are recorded only at discrete time points. Theoretical equations
      characterizing the population distribution of Cmax and Tmax are derived in
      relationship to the pharmacokinetic model, its parameters, their variabilities,
      and experimental errors. These equations can be solved by numerical integration.
      The resulting means, variances and other summary statistics of Cmax and Tmax are
      evaluated under various conditions involving single and multiple drug
      administrations. Results gained by the proposed numerical method agree closely
      with results gained by Monte-Carlo simulations. It is argued that the numerical
      method could be useful to study the statistical properties of the investigated
      measures and could, in some cases, provide a viable alternative to simulations.
      It is demonstrated that Cmax is estimated directly with positive bias, especially
      following repeated drug administrations. As a consequence, the recorded peak
      trough fluctuation (PTF), measured in the steady state, can be excessively large
      (even by orders of magnitude) particularly when drug accumulation is high. These
      results have practical implications for the development of drugs and drug
      formulations.

PMID- 14977166
TI  - On the origin of intracellular compartmentation and organized metabolic systems.
AB  - The history of the development of the ideas and research of organized metabolic
      systems during last three decades is shortly reviewed. The cell cytoplasm is
      crowded with solutes, soluble macromolecules such as enzymes, nucleic acids,
      structural proteins and membranes. The high protein density within the large
      compartments of the cells predominantly determines the major characteristics of
      cellular environment such as viscosity, diffusion and inhomogeneity. The fact
      that the solvent viscosity of cytoplasm is not substantially different from the
      water is explained by intracellular structural heterogeneity: the intrinsic
      macromolecular density is relatively low within the interstitial voids in the
      cell because many soluble enzymes are apparently integral parts of the insoluble
      cytomatrix and are not distributed homogeneously. The molecular crowding and
      sieving restrict the mobility of very large solutes, binding severely restrict
      the mobility of smaller solutes. One of consequence of molecular crowding and
      hindered diffusion is the need to compartmentalize metabolic pathway to overcome
      diffusive barriers. Although the movement of small molecules is slowed down in
      the cytoplasm, the metabolism can successfully proceed and even be facilitated by
      metabolite channeling which directly transfers the intermediate from one enzyme
      to an adjacent enzyme without the need of free aqueous-phase diffusion. The
      enhanced probability for intermediates to be transferred from one active site to
      the other by sequential enzymes requires stable or transient interactions of the
      relevant enzymes, which associate physically in non-dissociable, static
      multienzyme complexes--metabolones, particles containing enzymes of a part or
      whole metabolic systems. Therefore, within the living cell the metabolism depends
      on the structural organization of enzymes forming microcompartments. Since cells
      contain many compartments and microenvironments, the measurement of the
      concentration of metabolites in whole cells or tissues gives an average cellular
      concentration and not that which is actually sensed by the active site of a
      specific enzyme. Thus, the microcompartmentation could provide a mechanism which
      can control metabolic pathways. Independently and in parallel to the developments
      described above, the ideas of compartmentation came into existence from the
      necessity to explain important physiological phenomena, in particular in heart
      research and in cardiac electrophysiology. These phenomena demonstrated the
      physiological importance of the biophysical and biochemical mechanisms described
      in this review.

PMID- 14977167
TI  - Phosphotransfer dynamics in skeletal muscle from creatine kinase gene-deleted
      mice.
AB  - To assess the significance of energy supply routes in cellular energetic
      homeostasis, net phosphoryl fluxes catalyzed by creatine kinase (CK), adenylate
      kinase (AK) and glycolytic enzymes were quantified using 18O-phosphoryl labeling.
      Diaphragm muscle from double M-CK/ScCKmit knockout mice exhibited virtually no CK
      catalyzed phosphotransfer. Deletion of the cytosolic M-CK reduced CK-catalyzed
      phosphotransfer by 20%, while the absence of the mitochondrial ScCKmit isoform
      did not affect creatine phosphate metabolic flux. Contribution of the AK
      catalyzed phosphotransfer to total cellular ATP turnover was 15.0, 17.2, 20.2 and
      28.0% in wild type, ScCKmit, M-CK and M-CK/ScCKmit deficient muscles,
      respectively. Glycolytic phosphotransfer, assessed by G-6-P 18O-phosphoryl
      labeling, was elevated by 32 and 65% in M-CK and M-CK/ScCKmit deficient muscles,
      respectively. Inhibition of glyceraldehyde 3-phosphate dehydrogenase
      (GAPDH)/phosphoglycerate kinase (PGK) in CK deficient muscles abolished inorganic
      phosphate compartmentation and redirected high-energy phosphoryl flux through the
      AK network. Under such conditions, AK phosphotransfer rate was equal to 86% of
      the total cellular ATP turnover concomitant with almost normal muscle
      performance. This indicates that near-equilibrium glycolytic phosphotransfer
      reactions catalyzed by the GAPDH/PGK support a significant portion of the high
      energy phosphoryl transfer in CK deficient muscles. However, CK deficient muscles
      displayed aberrant ATPase-ATPsynthase communication along with lower energetic
      efficiency (P/O ratio), and were more sensitive to metabolic stress induced by
      chemical hypoxia. Thus, redistribution of phosphotransfer through glycolytic and
      AK networks contributes to energetic homeostasis in muscles under genetic and
      metabolic stress complementing loss of CK function.

PMID- 14977168
TI  - Structural and functional adaptations of striated muscles to CK deficiency.
AB  - In adult mammalian muscle cells, energy consuming processes are mainly localized
      to the sarcolemma, sarcoplasmic reticulum (SR) and myofibrillar compartments,
      while energy production occurs within mitochondria or glycolytic complexes. Due
      to the restricted diffusion of adenine nucleotides near the active sites of
      ATPases involved in contractile activity and calcium homeostasis, there are
      multiple local systems that can locally rephosphorylate ADP and provide ATP. The
      creatine kinase (CK) system, with specific isoenzymes localized within each
      compartment, efficiently controls local adenylate pools and links energy
      production and utilization. However, mice lacking one or both of the MM-CK and mi
      CK isoforms (CK-/-) are viable and develop almost normal cardiac and skeletal
      muscle function under the conditions of moderate workload, suggesting adaptations
      or other mechanisms that may ensure efficient energy transfer. While fixed CK is
      essentially important, other systems could also be involved as well, such as
      bound glycolytic enzymes or adenylate kinase. We have shown that, additionally, a
      direct functional interplay exists between mitochondria and sarcoplasmic
      reticulum, or between mitochondria and myofilaments in muscle cells, that
      catalyzes direct energy and signal transfer between organelles. In cardiac cells
      of CK-/- mice, marked cytoarchitectural modifications were observed, and direct
      adenine nucleotide channeling between mitochondria and organelles was very
      effective to rescue SR and myofilament functions. In fast skeletal muscles,
      increased oxidative capacity also indicates compensatory mechanisms. In mutant
      mice, mitochondrial capacity increases and a direct energy channeling occurs
      between mitochondria on one hand and ATP consuming sites on the other. However,
      these systems appear to be insufficient to fully compensate for the lack of CK at
      high workload. It can be concluded that local rephosphorylation of ADP is a
      crucial regulatory point in highly differentiated and organized muscle cells to
      ensure contractile diversity and efficiency and that the CK system is important
      to control energy fluxes and energy homeostasis.

PMID- 14977170
TI  - Two structurally distinct and spatially compartmentalized adenylate kinases are
      expressed from the AK1 gene in mouse brain.
AB  - Adenylate kinases (AK, EC 2.7.4.3) have been considered important enzymes for
      energy homeostasis and metabolic signaling. To gain a better understanding of
      their cell-specific significance we studied the structural and functional aspects
      of products of one adenylate kinase gene, AK1, in mouse tissues. By combined
      computer database comparison and Northern analysis of mRNAs, we identified
      transcripts of 0.7 and 2.0 kilobases with different 5' and 3' non-coding regions
      which result from alternative use of promoters and polyadenylation sites. These
      mRNAs specify two distinct proteins, AK1 and a membrane-bound AK1 isoform
      (AK1beta), which differ in their N-terminal end and are co-expressed in several
      tissues with high-energy demand, including the brain. Immunohistochemical
      analysis of brain tissue and primary neurons and astrocytes in culture
      demonstrated that AK1 isoforms are expressed predominantly in neurons. AK1beta,
      when tested in transfected COS-1 and N2a neuroblastoma cells, located at the
      cellular membrane and was able to catalyze phosphorylation of ADP in vitro. In
      addition, AK1beta mediated AMP-induced activation of recombinant ATP-sensitive
      potassium channels in the presence of ATP. Thus, two structurally distinct AK1
      isoforms co-exist in the mouse brain within distinct cellular locations. These
      enzymes may function in promoting energy homeostasis in the compartmentalized
      cytosol and in translating cellular energetic signals to membrane metabolic
      sensors.

PMID- 14977169
TI  - CK flux or direct ATP transfer: versatility of energy transfer pathways evidenced
      by NMR in the perfused heart.
AB  - How the myocardium is able to permanently coordinate its intracellular fluxes of
      ATP synthesis, transfer and utilization is difficult to investigate in the whole
      organ due to the cellular complexity. The adult myocardium represents a paradigm
      of an energetically compartmented cell since 50% of total CK activity is bound in
      the vicinity of other enzymes (myofibrillar sarcolemmal and sarcoplasmic
      reticulum ATPases as well as mitochondrial adenine nucleotide translocator, ANT).
      Such vicinity of enzymes is well known in vitro as well as in preparations of
      skinned fibers to influence the kinetic properties of these enzymes and thus the
      functioning of the subcellular organelles. Intracellular compartmentation has
      often been neglected in the NMR analysis of CK kinetics in the whole organ. It is
      indeed a methodological challenge to reveal subcellular kinetics in a working
      organ by a global approach such as NMR. To get insight in the energy transfer
      pathway in the perfused rat heart, we developed a combined analysis of several
      protocols of magnetization transfer associated with biochemical data and
      quantitatively evaluated which scheme of energetic exchange best describes the
      NMR data. This allows to show the kinetic compartmentation of subcellular CKs and
      to quantify their fluxes. Interestingly, we could show that the energy transfer
      pathway shifts from the phosphocreatine shuttle in the oxygenated perfused heart
      to a direct ATP diffusion from mitochondria to cytosol under moderate inhibition
      of ATP synthesis. Furthermore using NMR measured fluxes and the known kinetic
      properties of the enzymes, it is possible to model the system, estimate local ADP
      concentrations and propose hypothesis for the versatility of energy transfer
      pathway. In the normoxic heart, a 3-fold ADP gradient was found between
      mitochondrial intermembrane space, cytosol and ADP in the vicinity of ATPases.
      The shift from PCr to ATP transport observed when ATP synthesis decreases might
      result from a balance in the activity of two populations of ANT, either coupled
      or uncoupled to CK. We believe this NMR approach could be a valuable tool to
      reinvestigate the control of respiration by ADP in the whole heart reconciling
      the biochemical knowledge of mitochondrial obtained in vitro or in skinned fibers
      with data on the whole heart as well as to identify the implication of
      bioenergetics in the pathological heart.

PMID- 14977171
TI  - Organization and regulation of the cytosolic NADH metabolism in the yeast
      Saccharomyces cerevisiae.
AB  - Keeping a cytosolic redox balance is a prerequisite for living cells in order to
      maintain a metabolic activity and enable growth. During growth of Saccharomyces
      cerevisiae, an excess of NADH is generated in the cytosol. Aerobically, it has
      been shown that the external NADH dehydrogenase, Nde1p and Nde2p, as well as the
      glycerol-3-phosphate dehydrogenase shuttle, comprising the cytoplasmic glycerol-3
      phosphate dehydrogenase, Gpdlp, and the mitochondrial glycerol-3-phosphate
      dehydrogenase, Gut2p, are the most important mechanisms for mitochondrial
      oxidation of cytosolic NADH. In this review we summarize the recent results
      showing (i) the contribution of each of the mechanisms involved in mitochondrial
      oxidation of the cytosolic NADH, under different physiological situations; (ii)
      the kinetic and structural properties of these metabolic pathways in order to
      channel NADH from cytosolic dehydrogenases to the inner mitochondrial membrane
      and (iii) the organization in supramolecular complexes and, the peculiar ensuing
      kinetic regulation of some of the enzymes (i.e. Gut2p inhibition by external NADH
      dehydrogenase activity) leading to a highly integrated functioning of enzymes
      having a similar physiological function. The cell physiological consequences of
      such an organized and regulated network are discussed.

PMID- 14977172
TI  - Functional aspects of cellular microcompartmentation in the development of
      neurodegeneration: mutation induced aberrant protein-protein associations.
AB  - Research in the last 10 years has revealed that the development of
      neurodegeneration is a multistep process during which one or few specific mutant
      protein species of altered conformation initiate aberrant protein-protein
      interactions resulting in aggregates forming plaques. This review focuses on the
      heteroassociations of the mutant proteins with subcellular structures, such as
      cytoskeleton, cell membranes or with glycolytic enzymes, which may be crucial in
      the initiation of neurodegeneration such as in Huntington's disease or
      Alzheimer's disease. Triosephosphate isomerase enzymopathy is a unique glycolytic
      enzyme deficiency coupled with neurodegeneration. We present data on the mutation
      induced misfolding process, which likely plays a crucial role in the enhanced
      associations of the enzyme with the truncated fragment of the isomerase, with the
      red cell membrane or with the microtubular network. On the basis of our recent
      clinical and experimental results obtained with two compound heterozygote
      Hungarian brothers it became obvious that the mutations alone are not sufficient
      to explain the development of the neurological sympthomes. This underscores the
      fact that the mutations alone are not enough for the development of the clinical
      phenotype of a disease.

PMID- 14977173
TI  - Control of maximum metabolic rate in humans: dependence on performance
      phenotypes.
AB  - Borrowing from metabolic control analysis the concept of control coefficients or
      ci values, defined as fractional change in MMR/fractional change in the capacity
      of any given step in ATP turnover, we used four performance phenotypes to compare
      mechanisms of control of aerobic maximum metabolic rate (MMR): (i) untrained
      sedentary (US) subjects, as a reference group against which to compare (ii) power
      trained (PT), (iii) endurance trained (ET), and (iv) high altitude adapted native
      (HA) subject groups. Sprinters represented the PT group; long distance runners
      illustrated the ET group; and Andean natives represented the HA group. Numerous
      recent studies have identified contributors to control on both the adenosine
      triphosphate (ATP) supply side and the ATP demand side of ATP turnover. From the
      best available evidence it appears that at MMR all five of the major steps in
      energy delivery (namely, ventilation, pulmonary diffusion, cardiac output, tissue
      capillary--mitochondrial O2 transfer, and aerobic cell metabolism per se)
      approach an upper functional ceiling, with control strength being distributed
      amongst the various O2 flux steps. On the energy demand side, the situation is
      somewhat simplified since at MMR approximately 90% of O2-based ATP synthesis is
      used for actomyosin (AM) and Ca2+ ATPases; at MMR these two ATP demand rates also
      appear to be near an upper functional ceiling. In consequence, at MMR the control
      contributions or ci values are distributed amongst all seven major steps in ATP
      supply and ATP demand pathways right to the point of fatigue. Relative to US (the
      reference group), in PT subjects at MMR control strength shifts towards O2
      delivery steps (ventilation, pulmonary diffusion, and cardiac output); here
      physiological regulation clearly dominates MMR control. In contrast in ET and HA
      subjects at MMR control shifts towards the energy demand steps (AM and Ca2+
      ATPases), and more control strength is focussed on tissue level ATP supply and
      ATP demand. One obvious advantage of the ET and HA biochemical-level control is
      improved metabolite homeostasis. Additionally, with some reserve capacity in the
      O2 delivery steps, the focussing of control on ATP turnover at the tissue level
      has allowed nature to improve on an 'endurance machine' design.

PMID- 14977174
TI  - VDAC: the channel at the interface between mitochondria and the cytosol.
AB  - The mitochondrial outer membrane is not just a barrier but a site of regulation
      of mitochondrial function. The VDAC family of proteins are the major pathways for
      metabolite flux through the outer membrane. These can be regulated in a variety
      of ways and the integration of these regulatory inputs allows mitochondrial
      metabolism to be adjusted to changing cellular conditions. This includes total
      blockage of the flux of anionic metabolites leading to permeabilization of the
      outer membrane to small proteins followed by apoptotic cell death.

PMID- 14977175
TI  - VDAC and peripheral channelling complexes in health and disease.
AB  - VDAC changes its structure either voltage dependent in artificial membranes or
      physiologically by interaction with the c conformation of the adenine nucleotide
      translocator (ANT). This interaction creates contact sites and leads to a
      specific organisation of cytochrome c in the VDAC ANT complexes. The VDAC
      structure specific for contact sites thus generates a signal at the surface for
      several proteins in the cytosol to bind with high affinity such as hexokinase,
      glycerolkinase and Bax. If the VDAC binding site is not occupied by hexokinase,
      the VDAC ANT complex has two critical qualities: firstly, external Bax gets
      access to the cytochrome c and secondly the ANT stays in the c conformation that
      easily changes the structure to an unspecific uni-porter causing permeability
      transition. Activity of bound hexokinase protects against both, it hinders Bax
      binding and employs the ANT as specific anti-porter. The octamer of mitochondrial
      creatine kinase binds to VDAC from the inner surface of the outer membrane. This
      firstly hinders direct interaction between VDAC and ANT and secondly changes
      porin structure into low affinity for hexokinase and external Bax. Cytochrome c
      in the creatine kinase complex will be differently organised not accessible to
      Bax and the ANT is run as anti-porter by the active octamer. However, when free
      radicals cause dissociation of the octamer, VDAC interacts with the ANT with the
      same results as described above: Bax dependent cytochrome c release and risk of
      permeability transition pore opening.

PMID- 14977176
TI  - Energy flux modulation on the outer membrane of mitochondria by metabolically
      derived potential.
AB  - Voltage-dependent anion channels (VDACs) are the porins in the outer
      mitochondrial membrane allowing metabolite flux between mitochondria and the
      cytoplasm. The permeabilities of the VDACs to ATP(-4), ADP(3-), creatine
      phosphate2-, Pi2-, Pi-, and other charged metabolites depend on the membrane
      potential. But neither the existence of the electrical potential across the outer
      membrane of mitochondria, nor its generation mechanisms have been experimentally
      shown. In this work, the concept of metabolically-derived potential that could be
      generated on the outer membrane was developed further. The computational study of
      the quantitative models shows that a steady-state membrane potential above 40 mV
      may be generated across a membrane with VDACs, if the VDACs are considered to be
      non-permeable to K+ and Cl-. Free permeability of VDACs to these inorganic ions,
      mimicking VDACs biological behavior, decreases the potential to nearly 12 mV.
      This decrease does not result from the electrical shortening of the potential by
      K+ and Cl- fluxes, but is caused by the electrodynamic compartmentation of the
      charged metabolites influencing the Goldman fluxes and the enzyme activity
      determining the fluxes. The interaction of two cyclic steady-state fluxes of
      charged metabolites due to the synergetic superposition of the potentials
      generated by each of these fluxes was obtained, and the effect of amplification
      of one flux by the other was theoretically demonstrated. These calculations based
      on VDACs' known permeability-voltage characteristics indicate that there is a
      certain possibility that the cell energy metabolism is regulated on the outer
      membrane of mitochondria by the electrical potential generated by various
      metabolically-dependent mechanisms.

PMID- 14977177
TI  - Mitochondria and the Bcl-2 family proteins in apoptosis signaling pathways.
AB  - Two main intracellular apoptosis cascades, the receptor and the mitochondria
      pathway, have been identified. The mitochondrial pathway is controlled by the Bcl
      2 proteins. This protein family contains members with either pro- or anti
      apoptotic activity. When activated the pro-apoptotic multidomain proteins
      permeabilized the outer mitochondrial membrane, resulting in the release of
      proteins from the intermembrane space. Several proteins, including cytochrome c,
      Smac/DIABLO, HtrA2/Omi, endonuclease G and AIF, normally sequestered in the
      mitochondria induce or promote apoptosis once released into the cytosol.
      Although, apoptosis is an essential physiological process in multicellular
      organisms it is also involved in a wide range of pathological conditions.

PMID- 14977178
TI  - Alterations of the bioenergetics systems of the cell in acute and chronic
      myocardial ischemia.
AB  - The aim of the works presented here is to analyze the alterations induced by
      acute ischemia-reperfusion and chronic ischemia on mitochondrial function, in
      relation to alterations on heart function. Parameters of mitochondrial function
      were assessed on skinned fibers coming from isolated perfused rat hearts. The
      effects of chronic ischemia were studied on a rat model of left descending
      coronary artery stenosis. Two key events observed after acute ischemia
      reperfusion and chronic ischemia are the decrease (or the loss) of the
      stimulatory effect of creatine and the alteration of outer mitochondrial
      permeability to cytochrome c and ADP. Taken together, these effects indicate the
      alteration of the intermembrane space architecture leading to the loss of
      intracellular adenine nucleotides compartmentation and possibly of functional
      coupling of mitochondrial creatine kinase and adenine nucleotide translocase.
      These alterations result in the impairment of intracellular energy transfer
      (channeling) from mitochondria to ATP-utilizing sites located in the cytosol.
      This may play a significant role in ischemic injury and alterations in heart
      function. We show that these effects were prevented by effective cardioprotective
      strategies like ischemic preconditioning or pharmacological preconditioning by
      perfusion of mitochondrial ATP-sensitive potassium channel openers. We
      hypothesize that an open mitochondrial ATP-sensitive potassium channel during
      ischemia maintains the tight structure of the intermembrane space that is
      required to preserve the normal low outer membrane permeability to ADP and ATP.

PMID- 14977179
TI  - The fractal architecture of cytoplasmic organization: scaling, kinetics and
      emergence in metabolic networks.
AB  - In this work, we highlight the links between fractals and scaling in cells and
      explore the kinetic consequences for biochemical reactions operating in fractal
      media. Based on the proposal that the cytoskeletal architecture is organized as a
      percolation lattice, with clusters emerging as fractal forms, the analysis of
      kinetics in percolation clusters is especially emphasized. A key consequence of
      this spatiotemporal cytoplasmic organization is that enzyme reactions following
      Michaelis-Menten or allosteric type kinetics exhibit higher rates in fractal
      media (for short times and at lower substrate concentrations) at the percolation
      threshold than in Euclidean media. As a result, considerably faster and higher
      amplification of enzymatic activity is obtained. Finally, we describe some of the
      properties bestowed by cytoskeletal organization and dynamics on metabolic
      networks.

PMID- 14977180
TI  - Functional coupling as a basic mechanism of feedback regulation of cardiac energy
      metabolism.
AB  - In this review we analyze the concepts and the experimental data on the
      mechanisms of the regulation of energy metabolism in muscle cells. Muscular
      energetics is based on the force-length relationship, which in the whole heart is
      expressed as a Frank-Starling law, by which the alterations of left ventricle
      diastolic volume change linearly both the cardiac work and oxygen consumption.
      The second basic characteristics of the heart is the metabolic stability--almost
      constant levels of high energy phosphates, ATP and phosphocreatine, which are
      practically independent of the workload and the rate of oxygen consumption, in
      contrast to the fast-twitch skeletal muscle with no metabolic stability and rapid
      fatigue. Analysis of the literature shows that an increase in the rate of oxygen
      consumption by order of magnitude, due to Frank-Starling law, is observed without
      any significant changes in the intracellular calcium transients. Therefore,
      parallel activation of contraction and mitochondrial respiration by calcium ions
      may play only a minor role in regulation of respiration in the cells. The
      effective regulation of the respiration under the effect of Frank-Starling law
      and metabolic stability of the heart are explained by the mechanisms of
      functional coupling within supramolecular complexes in mitochondria, and at the
      subcellular level within the intracellular energetic units. Such a complex
      structural and functional organisation of heart energy metabolism can be
      described quantitatively by mathematical models.

PMID- 14977181
TI  - Regulation of cellular respiration in myoglobin-deficient mouse heart.
AB  - The regulation of cardiac O2 consumption according to energy demand is best
      studied in the intact organ by non-destructive methods, using probes detectable
      by their fluorescence or light absorption. However, myoglobin is normally present
      in high concentrations and swamps the cytochrome spectra, thereby bringing about
      an oxygen-dependent internal filter effect which quenches the fluorescence of
      probes. A viable myoglobin-deficient mouse strain (Myo(-/-)) has been generated
      previously and isolated perfused Myo(-/-) hearts are used here as an ideal model
      for studying mitochondrial metabolism by non-destructive optical methods. In this
      model we monitored the redox state of cytochrome aa3 and flavoprotein (Fp) during
      perturbations of myocardial work output upon changes in extracellular [Ca2+], KCl
      induced arrest and pacing. Increased consumption of energy and O2 led to a
      concomitant reduction of cytochrome aa3 and oxidation of Fp. Administration of a
      medium chain-length fatty acid caused a marked reduction of Fp, but even then an
      increase in energy consumption caused Fp oxidation. The results show that cell
      respiration in the intact myocardium is regulated at the site of the respiratory
      chain. Our findings do not support the NMR-based hypothesis that O2 consumption
      is mainly regulated at the level of intermediary metabolism and by the pressure
      of reducing equivalents to the mitochondrial respiratory chain.

PMID- 14977182
TI  - Interplay between mitochondria and cellular calcium signalling.
AB  - Mitochondria are increasingly ascribed central roles in vital cell signalling
      cascades. These organelles are now recognised as initiators and transducers of a
      range of cell signals, including those central to activation and amplification of
      apoptotic cell death. Moreover, as the main source of cellular ATP, mitochondria
      must be responsive to fluctuating energy demands of the cell. As local and global
      fluctuations in calcium concentration are ubiquitous in eukaryotic cells and are
      the common factor in a dizzying array of intra- and inter-cellular signalling
      cascades, the relationships between mitochondrial function and calcium transients
      is currently a subject of intense scrutiny. It is clear that mitochondria not
      only act as local calcium buffers, thus shaping spatiotemporal aspects of
      cytosolic calcium signals, but that they also respond to calcium uptake by
      upregulating the tricarboxylic acid cycle, thus reacting metabolically to local
      signalling. In this chapter we review current knowledge of mechanisms of
      mitochondrial calcium uptake and release and discuss the consequences of
      mitochondrial calcium handling for cell function, particularly in conjunction
      with mitochondrial oxidative stress.

PMID- 14977183
TI  - Studies of mitochondrial respiration in muscle cells in situ: use and misuse of
      experimental evidence in mathematical modelling.
AB  - Applications of permeabilized cell and skinned fiber techniques in combination
      with methods of mathematical modelling for studies of mitochondrial function in
      the cell are critically evaluated. Mathematical models may be useful tools for
      explaining biological phenomena, but only if they are selected by fitting the
      computing results with real experimental data. Confocal microscopy has been used
      in experiments with permeabilized cardiomyocytes and myocardial fibers to
      determine the maximal diffusion distance from medium to the core of cells, which
      is shown not to exceed 8-10 microm. This is a principal index for correctly
      explaining high apparent Km for exogenous ADP (200-300 microM) in regulation of
      mitochondrial respiration in oxidative muscle cells in situ. The best fitting of
      the results of in silico studies may be achieved by using of the
      compartmentalized energy transfer model. From these results, it may be concluded
      that in cardiac muscle cells the mitochondria and ATPases are organized into
      intracellular energetic units (ICEUs) separated from the bulk phase of cytoplasm
      by some barriers which limit the diffusion of adenine nucleotides. In contrast,
      alternative models based on the concept of the cell as homogenous system do not
      explain the observed experimental phenomena and have led to misleading
      conclusions. The various sources of experimental and conceptual errors are
      analyzed.

PMID- 14977184
TI  - Intracellular diffusion of adenosine phosphates is locally restricted in cardiac
      muscle.
AB  - Recent studies have revealed the structural and functional interactions between
      mitochondria, myofibrils and sarcoplasmic reticulum in cardiac cells. Direct
      channeling of adenosine phosphates between organelles identified in the
      experiments indicates that diffusion of adenosine phosphates is limited in
      cardiac cells due to very specific intracellular structural organization.
      However, the mode of diffusion restrictions and nature of the intracellular
      structures in creating the diffusion barriers is still unclear, and, therefore, a
      subject of active research. The aim of this work is to analyze the possible role
      of two principally different modes of restriction distribution for adenosine
      phosphates (a) the uniform diffusion restriction and (b) the localized diffusion
      limitation in the vicinity of mitochondria, by fitting the experimental data with
      the mathematical model. The reaction-diffusion model of compartmentalized energy
      transfer was used to analyze the data obtained from the experiments with the
      skinned muscle fibers, which described the following processes: mitochondrial
      respiration rate dependency on exogenous ADP and ATP concentrations; inhibition
      of endogenous ADP-stimulated respiration by pyruvate kinase (PK) and
      phosphoenolpyruvate (PEP) system; kinetics of oxygen consumption stabilization
      after addition of 2 mM MgATP or MgADP; ATPase activity with inhibited
      mitochondrial respiration; and buildup of MgADP concentration in the medium after
      addition of MgATP. The analysis revealed that only the second mechanism
      considered--localization of diffusion restrictions--is able to account for the
      experimental data. In the case of uniform diffusion restrictions, the model
      solution was in agreement only with two measurements: the respiration rate as a
      function of ADP or ATP concentrations and inhibition of respiration by PK + PEP.
      It was concluded that intracellular diffusion restrictions for adenosine
      phosphates are not distributed uniformly, but rather are localized in certain
      compartments of the cardiac cells.

PMID- 14977185
TI  - Nucleotide-gated KATP channels integrated with creatine and adenylate kinases:
      amplification, tuning and sensing of energetic signals in the compartmentalized
      cellular environment.
AB  - Transmission of energetic signals to membrane sensors, such as the ATP-sensitive
      K+ (KATP) channel, is vital for cellular adaptation to stress. Yet, cell
      compartmentation implies diffusional hindrances that hamper direct reception of
      cytosolic energetic signals. With high intracellular ATP levels, KATP channels
      may sense not bulk cytosolic, but rather local submembrane nucleotide
      concentrations set by membrane ATPases and phosphotransfer enzymes. Here, we
      analyzed the role of adenylate kinase and creatine kinase phosphotransfer
      reactions in energetic signal transmission over the strong diffusional barrier in
      the submembrane compartment, and translation of such signals into a nucleotide
      response detectable by KATP channels. Facilitated diffusion provided by creatine
      kinase and adenylate kinase phosphotransfer dissipated nucleotide gradients
      imposed by membrane ATPases, and shunted diffusional restrictions. Energetic
      signals, simulated as deviation of bulk ATP from its basal level, were amplified
      into an augmented nucleotide response in the submembrane space due to failure
      under stress of creatine kinase to facilitate nucleotide diffusion. Tuning of
      creatine kinase-dependent amplification of the nucleotide response was provided
      by adenylate kinase capable of adjusting the ATP/ADP ratio in the submembrane
      compartment securing adequate KATP channel response in accord with cellular
      metabolic demand. Thus, complementation between creatine kinase and adenylate
      kinase systems, here predicted by modeling and further supported experimentally,
      provides a mechanistic basis for metabolic sensor function governed by
      alterations in intracellular phosphotransfer fluxes.

PMID- 14977186
TI  - Random walk analysis of restricted metabolite diffusion in skeletal myofibril
      systems.
AB  - The purpose of this work was the development of a basal mathematical model for
      the diffusion of low-molecular metabolites in a skeletal muscle cell. A three
      dimension diffusion of low-molecular particles was simulated by a Monte-Carlo
      method (random walks of diffusing molecules). The model takes into account the
      following structural elements: (i) a regular lattice of actin and myosin
      filaments inside a myofibril; (ii) the membranes of sarcoplasmic reticulum and
      mitochondria surrounding the myofibrils; (iii) a set of myofibrils inside a
      skeletal muscle cell. We simulated diffusion of particles in the bulk of
      intracellular water phase and their reflections from the rigid surfaces of
      intracellular structures. The model allowed to calculate the apparent
      coefficients of particle diffusion in the axial and radial directions,
      Dparallel(app) and Dperpendicular(app), respectively. In accordance with
      experimental data from literature, the coefficient Dparallel(app) was independent
      of time. The coefficient of radial diffusion Dperpendicular(app) decreased with
      time to steady state values similar to that determined by the NMR diffusion
      spectroscopy methods. The interactions of diffusing particles with thin and thick
      filaments of myofibrils could explain the decrease in the Dperpendicular(app)
      value by a factor of 20%. The collisions of particles with myofilaments began to
      reveal themselves as a gradual decrease in the Dperpendicular(app) value at early
      stages of diffusion (t1/2 approximately equal to 0.05 microsec). The contribution
      of particle reflections from the membranes of sarcoplasmic reticulum and
      mitochondria to the retardation of the radial diffusion was about of 20-30%,
      depending on porosity of a membranous shield around the myofibril. For
      conventional sizes of a membranous shield (diameter 2 microm), the interactions
      of particles with the shield caused a decrease in the Dperpendicular(app) value
      with a half-time t1/2 approximately equal to 0.5 msec. This time is essentially
      lower by a factor about of 100 than that found in published NMR measurements.
      When we considered diffusion of particles inside a cell compartment confined to
      impermeable membranous shield, the reflection of particles from this shield led
      the drastic decrease in the radial diffusion coefficient (Dperpendicular(app) -->
      porportional to when t --> porportional to). This pattern of the
      Dperpendicular(app)(t) time-course might be expected in the NMR measurements on
      skeletal muscle tissue where a sarcolemma represents an impermeable shield for
      ATP and PCr molecules.

PMID- 14977187
TI  - Evaluation of quantitative and qualitative aspects of mitochondrial function in
      human skeletal and cardiac muscles.
AB  - Techniques and protocols of assessment of mitochondrial properties are of
      physiological and physiopathological important significance. A precise knowledge
      of the advantages and limitations of the different protocols used to investigate
      the mitochondrial function, is therefore necessary. This report presents examples
      of how the skinned (or permeabilized) fibers technique could be applied for the
      polarographic determination of the actual quantitative and qualitative aspects of
      mitochondrial function in human muscle samples. We described and compared the
      main available respiration protocols in order to sort out which protocol seems
      more appropriate for the characterization of mitochondrial properties according
      to the questions under consideration: quantitative determination of oxidative
      capacities of a given muscle, characterization of the pattern of control of
      mitochondrial respiration, or assessment of a mitochondrial defect at the level
      of the respiratory chain complexes. We showed that while protocol A, using only
      two levels of the phosphate acceptor adenosine diphosphate (ADP) concentration
      and the adjunction of creatine, could be used for the determination of
      quantitative changes in very small amount of muscle samples, the ADP sensitivity
      of mitochondrial respiration was underestimated by this protocol in muscles with
      high oxidative capacities. The actual apparent Km for ADP and the role of
      functional activation of miCK in ATP production and energy transfer in oxidative
      muscles, are well-assessed by protocol B (in the absence of creatine) together
      with protocol C (in the presence of creatine) that use increasing concentrations
      of ADP ranging from 2.5-2000 microM. Protocol D is well-adapted to investigate
      the potential changes at different levels of the respiratory chain, by the use of
      specific substrates and inhibitors. As can be seen from the present data and the
      current review of previous reports in the literature, a standardization of the
      respiration protocols is needed for useful comparisons between studies.

PMID- 14977188
TI  - Mapping hypoxia-induced bioenergetic rearrangements and metabolic signaling by
      18O-assisted 31P NMR and 1H NMR spectroscopy.
AB  - Brief hypoxia or ischemia perturbs energy metabolism inducing paradoxically a
      stress-tolerant state, yet metabolic signals that trigger cytoprotection remain
      poorly understood. To evaluate bioenergetic rearrangements, control and hypoxic
      hearts were analyzed with 18O-assisted 31P NMR and 1H NMR spectroscopy. The 18O
      induced isotope shift in the 31P NMR spectrum of CrP, betaADP and betaATP was
      used to quantify phosphotransfer fluxes through creatine kinase and adenylate
      kinase. This analysis was supplemented with determination of energetically
      relevant metabolites in the phosphomonoester (PME) region of 31P NMR spectra, and
      in both aromatic and aliphatic regions of 1H NMR spectra. In control conditions,
      creatine kinase was the major phosphotransfer pathway processing high-energy
      phosphoryls between sites of ATP consumption and ATP production. In hypoxia,
      creatine kinase flux was dramatically reduced with a compensatory increase in
      adenylate kinase flux, which supported heart energetics by regenerating and
      transferring beta- and gamma-phosphoryls of ATP. Activation of adenylate kinase
      led to a build-up of AMP, IMP and adenosine, molecules involved in
      cardioprotective signaling. 31P and 1H NMR spectral analysis further revealed
      NADH and H+ scavenging by alpha-glycerophosphate dehydrogenase (alphaGPDH) and
      lactate dehydrogenase contributing to maintained glycolysis under hypoxia.
      Hypoxia-induced accumulation of alpha-glycerophosphate and nucleoside 5'
      monophosphates, through alphaGPDH and adenylate kinase reactions, respectively,
      was mapped within the increased PME signal in the 31P NMR spectrum. Thus, 18O
      assisted 31P NMR combined with 1H NMR provide a powerful approach in capturing
      rearrangements in cardiac bioenergetics, and associated metabolic signaling that
      underlie the cardiac adaptive response to stress.

PMID- 14977189
TI  - IgG from patients with liver diseases inhibit mitochondrial respiration in
      permeabilized oxidative muscle cells: impaired function of intracellular
      energetic units?
AB  - The effect of IgG purified from the sera of healthy persons and patients with
      primary biliary cirrhosis (PBC) and chronic hepatitis (CH) on ADP dependent
      respiration (oxidative phosphorylation) in skinned muscle fibers from rat
      oxidative muscles (heart and M. soleus) and glycolytic skeletal muscle (M.
      gastrocnemius) was studied. The results show that IgG from three different
      sources inhibited the rate of respiration by 13, 44 and 42%, respectively, these
      effects being equally expressed in both types of oxidative muscles, whereas no
      inhibition was observed in glycolytic muscle. The following washout of unbound
      IgG did not abolish the inhibition of respiration suggesting that the specific
      interaction of IgG with antigens had taken place. Laser confocal analysis
      revealed binding of IgG predominantly to the sarcomeric structures such as Z-disk
      and M-lines in the cardiomyocytes. The staining of IgG within Z-disks and
      intermitochondrial space coincided throughout the muscle cells so that
      transversally serial spaces, each containing mitochondria and adjacent sarcomere,
      became clearly visible. When the IgG from a CH patient was incubated with the
      skinned myocardial fibers of the desmin knockout mice, its binding to Z-disks and
      the sarcomeric area was found to be similar to that in normal cardiac muscle.
      However, the transversal staining pattern was disintegrated, because of the
      slippage of the myofibrils in relation to each other and accumulation of
      mitochondria between them. These observations support the recent hypothesis that
      in oxidative muscles the mitochondria and adjacent sarcomeres form complexes,
      termed as the intracellular energetic units, ICEUs. Moreover, they indicate that
      human autoantibodies can be useful tools for localizing the proteins responsible
      for formation of ICEUs and modulation of their function. Thus, it appears that
      the proteins associated with the Z-disks and M-lines may participate in formation
      of ICEUs and that binding of IgG to these proteins decreases the access of
      exogenous adenine nucleotides to mitochondria, which manifests as decreased rate
      of ADP-dependent respiration.

PMID- 14977190
TI  - Mice lacking the UbCKmit isoform of creatine kinase reveal slower spatial
      learning acquisition, diminished exploration and habituation, and reduced
      acoustic startle reflex responses.
AB  - Brain-type creatine kinases B-CK (cytosolic) and UbCKmit (mitochondrial) are
      considered important for the maintenance and distribution of cellular energy in
      the central nervous system. Previously, we have demonstrated an abnormal
      behavioral phenotype in mice lacking the B-CK creatine kinase isoform, regarding
      exploration, habituation, seizure susceptibility and spatial learning. The
      phenotype in these mice was associated with histological adaptations in the
      hippocampal mossy fiber field size. Here, mice lacking the ubiquitous
      mitochondrial creatine kinase isoform (UbCKmit-/- mice) showed, when subjected to
      a similar battery of behavioral tasks, diminished open field habituation and
      slower spatial learning acquisition in the Morris water maze task, but normal
      sensory or motor functions. A reduced acoustic startle response, higher
      threshold, and lack of prepulse inhibition were observed in UbCKmit-/- mice,
      suggesting that the unconditioned reflexive responsiveness is not optimal. Our
      findings suggest a role for mitochondrial CK-mediated high-energy phosphoryl
      transfer in synaptic signalling in the acoustic signal response network and
      hippocampal-dependent learning circuitry of brain. Finally, we demonstrate that
      UbCKmit has a widespread occurrence in the cell soma of neuronal nuclei along the
      rostro-caudal axis of the brain, i.e. cortex, midbrain, hindbrain, cerebellum and
      brainstem, similar to the occurrence of B-CK. This may explain the similarity of
      phenotypes in mice lacking B-CK or UbCKmit. We predict that the remaining
      functional intactness of the cytosolic B-CK reaction and perhaps the compensatory
      role of other phosphoryl transfer systems are sufficient to sustain the energy
      requirements for basic sensory, motor and physiological activities in UbCKmit-/-
      mice.

PMID- 14977191
TI  - Trehalose-enzyme interactions result in structure stabilization and activity
      inhibition. The role of viscosity.
AB  - Stress resistance is essential for survival. The mechanisms of molecule
      stabilization during stress are of interest for biotechnology, where many enzymes
      and other biomolecules are increasingly used at high temperatures and/or salt
      concentrations. Diverse organisms, exhibit rapid synthesis and accumulation of
      the disaccharide trehalose in response to stress. Trehalose is also rapidly
      hydrolyzed as soon as stress ends. In isolated enzymes, trehalose stabilizes
      both, structure and activity. In contrast, at optimal assay conditions, trehalose
      inhibits enzyme activity. A general mechanism underlying the trehalose effects
      observed at all temperatures probably is the trehalose-mediated increase in
      solution viscosity that leads to protein domain motion inhibition. This may be
      analyzed using Kramer's theory. The role of viscosity in the effects of trehalose
      is analyzed in examples from the literature and in studies on the plasma membrane
      H(+)-ATPase from Kluyveromyces lactis. In the cell, it may be proposed that the
      large concentration of trehalose reached during stress stabilizes structures
      through viscosity. However, once stress ends trehalose has to be rapidly
      hydrolyzed in order to avoid the viscosity-mediated inhibition of enzymes.

PMID- 14977192
TI  - Mitochondrial morphology is dynamic and varied.
AB  - The morphology of mitochondria is dynamic, often changing within a cell and from
      one cell type to the next. In the past few years, significant advances have been
      made in the study of mechanisms that help determine the morphologies of
      mitochondria and their intracellular distributions. It has become apparent that
      the distribution of mitochondria is determined by movement along the
      cytoskeleton, driven by molecular motors, and attachment to the cytoskeleton,
      using specific connector proteins. However, not all cells use the same
      cytoskeletal elements and motor proteins for mitochondrial movement and
      attachment. The shapes of mitochondria are also influenced by the extent of
      mitochondrial division and fusion. A number of proteins that affect mitochondrial
      division and fusion were recently discovered. Here, we review the proteins
      involved in the distribution and morphology of mitochondria and discuss how they
      may be physiologically regulated.

PMID- 14977193
TI  - Thread-grain transition of mitochondrial reticulum as a step of mitoptosis and
      apoptosis.
AB  - Association of mitochondrial population to a mitochondrial reticulum is typical
      of many types of the healthy cells. This allows the cell to organize a united
      intracellular power-transmitting system. However, such an association can create
      some difficulties for the cell when a part of the reticulum is damaged or when
      mitochondria should migrate from one cell region to another. It is shown that in
      these cases decomposition of extended mitochondria to small roundish organelles
      takes place (the thread-grain transition). As an intermediate step of this
      process, formation of beads-like mitochondria occurs when several swollen parts
      of the mitochondrial filament are interconnected with thin thread-like
      mitochondrial structures. A hypothesis is put forward that the thread-grain
      transition is used as a mechanism to isolate a damaged part of the mitochondrial
      system from its intact parts. If the injury is not repaired, spherical
      mitochondrion originated from the damaged part of the reticulum is assumed to
      convert to a small ultracondensed and presumably dead mitochondrion (this process
      is called 'mitoptosis'). Then the dead mitochondrion is engulfed by an
      autophagosome. Sometimes, an ultracondensed mitoplast co-exists with a normal
      mitoplast, both of them being surrounded by a common outer mitochondrial
      membrane. During apoptosis, massive thread-grain transition is observed which,
      according to Youle et al. (S. Frank et al., Dev Cell 1: 515, 2002), is mediated
      by a dynamin-related protein and represents an obligatory step of the
      mitochondria-mediated apoptosis. We found that there is a lag phase between
      addition of an apoptogenic agent and the thread-grain transition. When started,
      the transition occurs very fast. It is also found that this event precedes
      complete de-energization of mitochondria and cytochrome c release to cytosol.
      When formed, small mitochondria migrate to (and in certain rare cases even into)
      the nucleus. It is suggested that small mitochondria may serve as a transportable
      form of organelles ('cargo boats' transporting some apoptotic proteins to their
      nuclear targets).

PMID- 14977194
TI  - Subcellular heterogeneity of mitochondrial function and dysfunction: evidence
      obtained by confocal imaging.
AB  - Beyond their fundamental role in energy metabolism, mitochondria perform a great
      variety of other important functions (e.g. in Ca2+ homeostasis, apoptosis,
      thermogenesis, etc.), thus suggesting their region-specific specializations and
      intracellular heterogeneity. Although mitochondrial functional heterogeneity has
      been demonstrated for several cell types, its origin and role under physiological
      and, in particular, pathophysiological conditions, where the extent of
      heterogeneity may significantly increase, remain to be elucidated. The present
      work thus investigated the static and dynamic heterogeneity of mitochondria and
      mitochondrial function in various cell types in which mitochondria may cope with
      specific functions including cardiomyocytes, hepatocytes and some cultured
      carcinoma cells. Modern confocal and two-photon fluorescent microscopy was used
      for the investigation and direct imaging of region-specific mitochondrial
      function and heterogeneity. Analysis of the autofluorescence of mitochondrial
      flavoproteins in hepatocytes and carcinoma cells permitted significant
      intracellular heterogeneity of mitochondrial redox state to be demonstrated.
      Comparative homogeneity and clear colocalization of mitochondrial flavoproteins,
      membrane potential and calcium-sensitive probes were observed in both isolated
      cardiomyocytes and permeabilized myocardial fibers. After ischemia reperfusion,
      however, or under conditions of substrate deprivation, significant heterogeneity
      of all these parameters was detected. Some methodological issues, mechanistic
      aspects, possible metabolic consequences of mitochondrial functional
      heterogeneity and its impact under pathological conditions are discussed.

PMID- 14977195
TI  - Subcellular heterogeneity in mitochondrial red-ox responses to KATP channel
      agonists in freshly isolated rabbit cardiomyocytes.
AB  - We have used the technique of fluorescent microscopy imaging supplemented with
      the refined analysis of temporal cartography of the cell fluorescence to
      investigate the mechanisms of regulation of mitochondrial function and its red-ox
      state in cardiac cells in vivo. Autofluorescence of flavoproteins of the
      respiratory chain in the isolated rabbit cardiomyocytes was registered before and
      after application of mitochondrial KATP channel opener diazoxide (100 and 400
      microM). Diazoxide addition resulted in oxidation of flavoproteins. Detailed
      analysis of these responses showed that they were heterogeneous over space and
      time. The local responses show rapid jumps. In a few cells, metabolic
      oscillations developed and could be recorded for tens of minutes. Under these
      conditions the cells appeared divided into a small number of regions in which
      mitochondria function synchronously. Local pattern of oxidation switches again
      and again from a reduced state to the same level of oxidation. All these
      phenomena where absent when the cells were permeabilized by saponin giving a
      direct access to mitochondrial KATP channel opener. Cross-correlation analysis
      revealed a high degree of homogeneity for cells presenting metabolic
      oscillations, contrarily to those displaying a smooth increase in fluorescence in
      response to diazoxide. The results are consistent with the view that mitochondria
      form independent functional units whose behaviour can be synchronised by some
      unknown cellular factors or metabolites.

PMID- 14977196
TI  - Inhibitors of SERCA and mitochondrial Ca-uniporter decrease velocity of calcium
      waves in rat cardiomyocytes.
AB  - Spontaneous calcium waves in isolated rat cardiomyocytes were investigated by
      confocal laser scanning microscopy using the fluorescent Ca(2+)-indicator fluo-4
      AM. With increasing calcium overload propagation velocities reinforced. The
      calcium wavespeed was significantly diminished by drugs which interfere with the
      calcium uptake of both the sarcoplasmic reticulum (SR) and mitochondria,
      respectively. Stepwise addition of thapsigargin, a highly specific inhibitor of
      SERCA, decreased the wavespeed and allowed the determination of flux control
      coefficients which were found to be increasing from 0.15-0.75 in dependence on
      calcium overload. Kd was estimated to be between 0.4 and 0.6 nM TG. At 5 mM TG
      wavespeed was significantly reduced by almost 50%. Spontaneous calcium waves did
      not occur in bathing solutions with more than 20 nM thapsigargin. Calcium wave
      velocity was also reduced in the presence of the oxygen-bridged dinuclear
      ruthenium amine complex RU 360 which specifically blocks the mitochondrial Ca2+
      uptake. The observed effects are likely due to a reduction of the ryanodine
      receptor's open probability. It is suggested that the intracellular Ca2+
      signaling depends on both SR lumenal and cytosolic calcium concentration.

PMID- 14977197
TI  - The velocity of calcium waves is expected to depend non-monotoneously on the
      density of the calcium release units.
AB  - In this paper we develop a reaction-diffusion system describing the calcium
      dynamics in an agarose gel system with resuspended vesicles from the sarcoplasmic
      reticulum (SR vesicles). We focus on a simple model: compared with living cells
      (e.g. cardiac myocytes) an important property of the agarose gel system is the
      absence of the sarcolemma and the spatial separation of the calcium release units
      (CRUs). Our model includes the kinetics of ryanodine sensitive receptors (RyRs),
      the activity of the SERCA pumps and the diffusion of free calcium. We describe
      numerical simulations which show a biphasic relationship between the density of
      the CRUs and the propagation velocity of spreading waves. The non-monotony can be
      explained by changes in the amplitude of the local calcium concentration. We
      formulate implications for the in vitro system which could be verified in future
      experiments.

PMID- 14977198
TI  - Energetic depression caused by mitochondrial dysfunction.
AB  - Mitochondria, providing most of ATP needed for cell work, realizing numerous
      specific functions as biosyntheses or degradations, contributing to Ca2+
      signalling also play a key role in the pathways to cell death. Impairment of
      mitochondrial functions caused by mutations of mt-genome and by acute processes
      are responsible for numerous diseases. The relations between changes on the level
      of molecules and the clinical state are rather complex, and the prediction of
      thresholds is difficult. Therefore investigations on different levels of an
      organismus (genome, metabolites, enzymes, mitochondrial function in vivo and in
      vitro) are necessary (multi level approach). Metabolic control theory is a
      valuable tool for understanding the different effects of mutations on the level
      of enzyme activities and mitochondrial function. Decreased concentrations of
      adenine nucleotides, leaky outer and inner mitochondrial membranes, decreased
      rates of mitochondrial linked pathways and decreased activities of respiratory
      chain enzymes contribute to depression of cellular energy metabolism
      characterized by decreased cytosolic phosphorylation potentials as one of the
      most important consequences of mitochondrial impairments. This review regards
      classical bioenergetic mechanisms of mitochondrial impairment which contribute to
      energetic depression.

PMID- 14977200
TI  - The "Mozart effect": an electroencephalographic analysis employing the methods of
      induced event-related desynchronization/synchronization and event-related
      coherence.
AB  - The event-related responses of 18 individuals were recorded while they were
      listening to 3 music clips of 6 s duration which were repeated 30 times each. The
      music clips differed in the level of their complex structure, induced mood,
      musical tempo and prominent frequency. They were taken from Mozart's sonata (K.
      448), and Brahms' Hungarian dance (no. 5). The third clip was a simplified
      version of the theme taken from Haydn's symphony (no. 94) played by a computer
      synthesizer. Significant differences in induced event-related desynchronization
      between the 3 music clips were only observed in the lower-1 alpha band which is
      related to attentional processes. A similar pattern was observed for the
      coherence measures. While respondents listened to the Mozart clip, coherence in
      the lower alpha bands increased more, whereas in the gamma band a less pronounced
      increase was observed as compared with the Brahms and Haydn clips. The clustering
      of the three clips based on EEG measures distinguished between the Mozart clip on
      the one hand, and the Haydn and Brahms clips on the other, even though the Haydn
      and Brahms clips were at the opposite extremes with regard to the mood they
      induced in listeners, musical tempo, and complexity of structure. This would
      suggest that Mozart's music--with no regard to the level of induced mood, musical
      tempo and complexity--influences the level of arousal. It seems that modulations
      in the frequency domain of Mozart's sonata have the greatest influence on the
      reported neurophysiological activity.

PMID- 14977199
TI  - Creatine transporters: a reappraisal.
AB  - Creatine (Cr) plays a key role in cellular energy metabolism and is found at high
      concentrations in metabolically active cells such as skeletal muscle and neurons.
      These, and a variety of other cells, take up Cr from the extra cellular fluid by
      a high affinity Na(+)/Cl(-)-dependent creatine transporter (CrT). Mutations in
      the crt gene, found in several patients, lead to severe retardation of speech and
      mental development, accompanied by the absence of Cr in the brain. In order to
      characterize CrT protein(s) on a biochemical level, antibodies were raised
      against synthetic peptides derived from the N- and C-terminal cDNA sequences of
      the putative CrT-1 protein. In total homogenates of various tissues, both
      antibodies, directed against these different epitopes, recognize the same two
      major polypetides on Western blots with apparent Mr of 70 and 55 kDa. The C
      terminal CrT antibody (alpha-CrTCOOH) immunologically reacts with proteins
      located at the inner membrane of mitochondria as determined by immuno-electron
      microscopy, as well as by subfractionation of mitochondria. Cr-uptake experiments
      with isolated mitochondria showed these organelles were able to transport Cr via
      a sulfhydryl-reagent-sensitive transporter that could be blocked by anti-CrT
      antibodies when the outer mitochondrial membrane was permeabilized. We concluded
      that mitochondria are able to specifically take-up Cr from the cytosol, via a low
      affinity CrT, and that the above polypeptides would likely represent
      mitochondrial CrT(s). However, by mass spectrometry techniques, the
      immunologically reactive proteins, detected by our anti-CrT antibodies, were
      identified as E2 components of the alpha-keto acid dehydrogenase multi enzyme
      complexes, namely pyruvate dehydrogenase (PDH), branched chain keto acid
      dehydrogenase (BC-KADH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH). The
      E2 components of PDH are membrane associated, whilst it would be expected that a
      mitochondrial CrT would be a transmembrane protein. Results of phase partitioning
      by Triton X-114, as well as washing of mitochondrial membranes at basic pH,
      support that these immunologically cross-reactive proteins are, as expected for
      E2 components, membrane associated rather than transmembrane. On the other hand,
      the fact that mitochondrial Cr uptake into intact mitoplast could be blocked by
      our alpha-CrTCOOH antibodies, indicate that our antisera contain antibodies
      reactive to proteins involved in mitochondrial transport of Cr. The presence of
      specific antibodies against CrT is supported by results from plasma membrane
      vesicles isolated from human and rat skeletal muscle, where both 55 and 70 kDa
      polypeptides disappeared and a single polypeptide with an apparent
      electrophoretic mobility of approximately 60 kDa was enriched. This latter is
      most likely representing the genuine plasma membrane CrT. Due to the fact that
      all anti-CrT antibodies that were independently prepared by several laboratories
      seem to cross-react with non-CrT polypeptides, specifically with E2 components of
      mitochondrial dehydrogenases, further research is required to characterise on a
      biochemical/biophysical level the CrT polypeptides, e.g. to determine whether the
      approximately 60 kDa polypeptide is indeed a bona-fide CrT and to identify the
      mitochondrial transporter that is able to facilitate Cr-uptake into these
      organelles. Therefore, the anti-CrT antibodies available so far should only be
      used with these precautions in mind. This holds especially true for quantitation
      of CrT polypeptides by Western blots, e.g. when trying to answer whether CrT's
      are up- or down-regulated by certain experimental interventions or under
      pathological conditions. In conclusion, we still hold to the scheme that besides
      the high-affinity and high-efficiency plasmalemma CrT there exists an additional
      low affinity high Km Cr uptake mechanism in mitochondria. However, the exact
      biochemical nature of this mitochondrial creatine transport, still remains
      elusive. Finally, similar to the creatine kinase (CK) isoenzymes, which are
      specifically located at different cellular compartments, also the substrates of
      CK are compartmentalized in cytosolic and mitochondrial pools. This is in line
      with 14C-Cr-isotope tracer studies and a number of [31P]-NMR magnetization
      transfer studies, as well as with recent [1H]-NMR spectroscopy data.

PMID- 14977201
TI  - Localization of slow wave activity in patients with tumor-associated epilepsy.
AB  - OBJECTIVE: Brain tumors are frequently accompanied by abnormal low frequency
      magnetic activity (ALFMA). The prevalence and clinical meaning of ALFMA are not
      well known, although a relation with epileptic brain tissue has been suggested.
      We studied the prevalence, characteristics and clinical correlates of ALFMA in 20
      patients with brain tumors. METHODS: In 20 patients with clinical seizures due to
      a supratentorial tumor, MEG was performed, followed by MR imaging. MEG signals
      were band pass-filtered (1-4 Hz); the sources of this activity were localized and
      projected onto the MRI of the patient. RESULTS: Peritumoral ALFMA could be
      detected in 13 of 20 patients. A pattern of ALFMA distribution around the tumor
      could be recognized. In eight cases ALFMA also appeared to be localized within
      the tumor. In three cases ALFMA was also detected in peritumoral white matter.
      CONCLUSIONS: Automatic detection of abnormal delta-activity in patients with a
      brain tumor and seizures can be performed in a clinical setting. When detected,
      ALFMA is mostly present in circumscribed regions around the tumor. Presence of
      ALFMA within the tumor might be an important warning signal for the neurosurgeon
      that the tumor area comprises functional brain tissue.

PMID- 14977202
TI  - Using the international 10-20 EEG system for positioning of transcranial magnetic
      stimulation.
AB  - BACKGROUND: The International 10-20 system for EEG electrode placement is
      increasingly applied for the positioning of transcranial magnetic stimulation
      (TMS) in cognitive neuroscience and in psychiatric treatment studies. The crucial
      issue in TMS studies remains the reliable positioning of the coil above the skull
      for targeting a desired cortex region. In order to asses the precision of the 10
      20 system for this purpose, we tested its projections onto the underlying cortex
      by using neuronavigation. METHODS: In 21 subjects, the 10-20 positions F3, F4,
      T3, TP3, and P3, as determined by a 10-20 positioning cap, were targeted
      stereotactically. The corresponding individual anatomical sites were identified
      in the Talairach atlas. RESULTS: The main targeted regions were: for F3 Brodmann
      areas (BA) 8/9 within the dorsolateral prefrontal cortex, for T3 BA 22/42 on the
      superior temporal gyrus, for TP3 BA 40/39 in thearea of the supramarginal and
      angular gyrus, and for P3 BA 7/40 on the inferior parietal lobe. However, in
      about 10% of the measurements adjacent and possibly functionally distinct BAs
      were reached. The ranges were mainly below 20 mm. CONCLUSION: Using the 10-20
      system for TMS positioning is applicable at low cost and may reach desired cortex
      regions reliably on a larger scale level. For finer grained positioning, possible
      interindividual differences, and therefore the application of neuroimaging based
      methods, are to be considered.

PMID- 14977203
TI  - Temporal stability of high-frequency brain oscillations in the human EEG.
AB  - Temporal stability of a given measurement within individual participants is a
      desirable property of psychophysiological measures. The present study aims to
      examine the reliability of high-frequency oscillatory activity in the human
      electroencephalogram (EEG) across 4 sessions. Convolution of the EEG time series
      with Morlet wavelets yielded time-frequency representations of the signal for
      each session. Stability of both topography and time course of gamma-band activity
      (GBA) was determined for two participants performing a feature-based selective
      attention task in four separate sessions, spaced at weekly intervals. We found
      high temporal stability of non-phase-locked GBA typically occurring in time
      ranges between 200 and 500 ms following presentation of a stimulus, both in terms
      of topography and time course. Early phase-locked GBA (80-120 ms) showed higher
      variability with respect to topography, but was consistent in terms of time
      course. We conclude that measures of high-frequency oscillatory activity as used
      in the cognitive neurosciences meet stability requirements necessary for
      meaningful interpretation of this parameter of brain function.

PMID- 14977204
TI  - 3-d source localization of epileptic foci integrating EEG and MRI data.
AB  - This study evaluates the utility of 3-D localization of interictal spike activity
      on the electroencephalographs (EEG) superimposed on magnetic resonance imagery
      (MRI) in a pediatric population with extra-temporal lesional epileptic foci. 3-D
      software programming based on the CURRY platform (a multimodal neuro-imaging
      software) was adapted for analyzing scalp EEG data and reconstructing
      superimposed images in 10 children who underwent extensive pre-surgical
      evaluation for intractable partial seizures. The results of 3-D spike source
      localization were assessed in relationship to focal lesions evident on the
      patient's MRI scans. Calculated spike sources were closest to the lesions during
      intervals corresponding to the spike peaks. The information was useful in
      surgical planning in six children that underwent successful resections.

PMID- 14977205
TI  - Advances in neuroprotection research for neurodegenerative diseases.

PMID- 14977206
TI  - Neurotransmitter release in experimental stroke models: the role of glutamate
      GABA interaction.

PMID- 14977207
TI  - Neuroprotection in ischemic/hypoxic disorders: from the preclinical to the
      clinical testing.

PMID- 14977208
TI  - Neuroprotection and dopamine agonists.

PMID- 14977209
TI  - Comt inhibition in the treatment of Parkinson's disease: neuroprotection and
      future perspectives.

PMID- 14977210
TI  - Neuroprotection and epilepsy.
AB  - During the last years it has become obvious that the current way of treating
      epilepsy with antiepeileptic drugs is insufficient concerning the modification of
      the underlying disesease and provides merely a symptomatic treatment, without
      clear influence on the course of the disease. There is a pressing need to find
      alternative strategies and to find possibilities to intervene either into the
      basic processes determining the development of epilepsies or to promote
      compensatory processes in repairing these dysfunctions. The increasing knowledge
      about the basic neuronal changes underlying epilepsies allows now to analyse the
      potential role of neuroprotective agents in in epileptogenesis. In epilepsy the
      most frequent constellation is the presence of damage and overexcitation
      together. Increase in excitability may develop after a primary damage as in
      posttraumatic epilepsy, or outburst of epileptic excitability may cause neuronal
      damage as in cell loss after status epilepticus or in any case of the so called
      cytotoxic damage from extensive glutamatergic involvement. Epilepsy in certain
      forms is a progressive disease. The factors determining the progressive course
      and the possibe prevention of it is obviously an overlaping field with
      neuroprotection. Therefore although neuroprotection works only against certain
      aspects of a complex cascade of pathological events, might be a promising option
      in several stadiums during the development and course of epilepsy. We provide
      evidences that some of the new antiepileptic drugs have neuroprotective effect on
      different animal models of chronic partial epilepsies, and how this effect is
      fitting to the antiepileptogenic, and seizure supressing effect of the same
      drugs.

PMID- 14977211
TI  - Neuroprotection and glatiramer acetate: the possible role in the treatment of
      multiple sclerosis.

PMID- 14977212
TI  - Causes and consequences of disturbances of cerebral glucose metabolism in
      sporadic Alzheimer disease: therapeutic implications.
AB  - Alzheimer disease is not a single disorder. Etiologically, two different types or
      even diseases exist: inheritance in 5% to 10% of all Alzheimer cases versus 90%
      to 95% AD cases whith sporadic origin (SAD). Different susceptibility genes along
      with adult lifestyle risk-factors- in the case of SAD the risk factor aging- may
      be assumed to cause the latter disorder. There is evidence that a disturbance in
      the insulin signal transduction pathway may be a central and early
      pathophysiologic event in SAD. Both, hypercortisolemia and increased adrenergic
      activity, in both old age and SAD may render the function of the neuronal insulin
      receptor vulnerable resulting in a diminished production of ATP. The reduced
      availability of ATP may damage the function of the endoplasmic reticulum/Golgi
      apparatus/trans Golgi network generating misfolded and malfolded proteins
      retained in the cell. In SAD, amyloid precursor protein is found to accumulate
      intracellularly thus not representing the cause but a driving force in the
      pathogenesis of SAD. Additionally, both disturbed insulin signaling and reduced
      ATP forward the hyperphosphorylation of tau protein. Thus, abnormalities in
      oxidative brain metabolism lead to the formation of two main morphologic
      hallmarks of SAD: senile plaques and neurofibrillary tangles. Therefore, the
      therapeutic goal in SAD should be the improvement of the neuronal energy state.
      Findings from both basic and clinical studies showed that Ginkgo biloba extract
      (EGb 761) may be appropiate to approach that goal.

PMID- 14977214
TI  - Kynurenines in neurodegenerative disorders: therapeutic consideration.

PMID- 14977213
TI  - Neuroprotection: a realistic goal for aged brain?

PMID- 14977215
TI  - Biomechanical interactions in tissue engineering and surgical repair (BITES).

PMID- 14977216
TI  - Assessment of cartilage thickness utilising reflectance spectroscopy.
AB  - A new principle for cartilage layer thickness assessments in joints is presented.
      It is based on the differences between the absorption spectra of cartilage and
      subchondral bone (containing blood). High-resolution ultrasound measurements of
      cartilage thickness were compared with reflection spectroscopy data from the same
      area of bovine hip joint condyles. A simple mathematical model allowed
      calculation of thickness and comparison with ultrasound data. The cartilage
      thickness was changed by being ground in short episodes. For thicker cartilage
      layers, a high degree of reflection in the 400-600 nm wavelength interval was
      seen. For thinner cartilage layers, the characteristics of the spectra of blood
      and bone dominated those of cartilage. The mean (+/- SD) thickness of intact
      cartilage was 1.21 +/- 0.30 mm (n = 30). In an exponential regression model,
      spectroscopic estimation of cartilage thickness showed a correlation coefficient
      of r = 0.69 (n = 182). For thinner cartilage layers (d < 0.5 mm), the mean model
      error was 0.19 +/- 0.17 mm. Results from a bi-layer Monte Carlo simulation
      supported the assumption of an exponential relationship between spectroscopy data
      and reference ultrasound data. The conclusion is that optical reflection
      spectroscopy can be used for cartilage layer thickness assessment.

PMID- 14977217
TI  - Effect of a degraded core on the mechanical behaviour of tissue-engineered
      cartilage constructs: a poro-elastic finite element analysis.
AB  - The structure and functionality of tissue-engineered cartilage is determined by
      the tissue culture conditions and mechanical conditioning during growth. The
      quality of tissue-engineered cartilage can be evaluated using tests such as the
      confined compression test. Tissue-engineered cartilage constructs usually consist
      of an outer layer of cartilage and an inner core of either undeveloped cartilage
      or degrading scaffold material. A biphasic poro-elastic finite element model was
      used to demonstrate how such a core influences the reaction force-time curve
      obtained from a confined compression test. The finite element model predicted
      that higher volumes of degraded scaffold in the inner core would reduce the
      aggregate modulus calculated from the confined compression test and raised the
      estimate of tissue permeability. The predicted aggregate modulus reduced from
      0.135 MPa, for a homogenous construct, to 0.068 MPa, for a construct that was
      only 70% cartilaginous. It was found that biphasic poro-elastic finite modelling
      should be used in preference to a one-dimensional model that assumed homogeneity
      in estimating the properties of tissue-engineered cartilage.

PMID- 14977218
TI  - Mechanotransduction of bone cells in vitro: mechanobiology of bone tissue.
AB  - Mechanical force plays an important role in the regulation of bone remodelling in
      intact bone and bone repair. In vitro, bone cells demonstrate a high
      responsiveness to mechanical stimuli. Much debate exists regarding the critical
      components in the load profile and whether different components, such as fluid
      shear, tension or compression, can influence cells in differing ways. During
      dynamic loading of intact bone, fluid is pressed through the osteocyte
      canaliculi, and it has been demonstrated that fluid shear stress stimulates
      osteocytes to produce signalling molecules. It is less clear how mechanical loads
      act on mature osteoblasts present on the surface of cancellous or trabecular
      bone. Although tissue strain and fluid shear stress both cause cell deformation,
      these stimuli could excite different signalling pathways. This is confirmed by
      our experimental findings, in human bone cells, that strain applied through the
      substrate and fluid flow stimulate the release of signalling molecules to varying
      extents. Nitric oxide and prostaglandin E2 values increased by between two- and
      nine-fold after treatment with pulsating fluid flow (0.6 +/- 0.3 Pa). Cyclic
      strain (1000 microstrain) stimulated the release of nitric oxide two-fold, but
      had no effect on prostaglandin E2. Furthermore, substrate strains enhanced the
      bone matrix protein collagen I two-fold, whereas fluid shear caused a 50%
      reduction in collagen I. The relevance of these variations is discussed in
      relation to bone growth and remodelling. In applications such as tissue
      engineering, both stimuli offer possibilities for enhancing bone cell growth in
      vitro.

PMID- 14977219
TI  - Effects of substrate characteristics on bone cell response to the mechanical
      environment.
AB  - The effect of substrate characteristics on primary human bone cell response to
      mechanical loading was investigated in this study. The substrates comprised
      organic and inorganic materials with a range of hydrophilic and hydrophobic
      features. Substrate surface topography varied from smooth to particulate to
      porous. It was found that hydrophilic substrates such as borosilicate glass
      facilitated bone cell adhesion, in contrast to hydrophobic substrates such as
      poly(L-lactic acid), in which clumps of cells grew unevenly across the substrate
      surface. All primary bone cells cultured in the various collagen-coated
      substrates were responsive to mechanical stimulation. The study showed that, at a
      low strain level of 1000 microstrain, mechanical stimulation enhanced bone cell
      differentiation rather than proliferation. Coating the substrates with collagen
      type I enhanced cell adhesion and promoted an elongated cell morphology,
      indicating that the presence of specific binding sites on a substrate may be more
      important than its hydrophilic properties, regardless of the substrate
      topography.

PMID- 14977220
TI  - Investigating body motion patterns in patients with Parkinson's disease using
      matching pursuit algorithm.
AB  - Several recent studies have quantified abnormalities in Parkinsonian gait.
      However, few studies have attempted to quantify the regularity of body motion
      during walking in patients with Parkinson's disease. The aim of the paper was to
      characterise body motion patterns in healthy, elderly subjects and patients with
      Parkinson's disease during walking. Body motion was recorded during walking for
      16 patients with Parkinson's disease and ten healthy, elderly subjects using a
      tri-axial accelerometer device. To characterise the body motion patterns, time
      frequency patterns of the body acceleration signal were estimated using a
      matching pursuit algorithm. Data from the study showed that the healthy, elderly
      subjects and patients with Parkinson's disease had different time-frequency
      patterns. The time-frequency patterns were classified into four distinct patterns
      based on their time durations: vertical (< 0.15 s), circular (0.15-0.5 s), short
      horizontal (0.5-2.0 s) and long horizontal (> 2.0 s). The data showed that the
      energy of the long horizontal patterns, representing long-term smooth and regular
      (rhythmic) activities, significantly decreased, but the energy of the circular
      patterns, representing irregular activities, increased in the patients with mild
      Parkinson's disease, compared with those of the healthy, elderly subjects (p <
      0.01). Futhermore, these features were seen more clearly in the body motions of
      severe case patients than is that of mild case patients. It was concluded that
      these differences are probably due to a lack of ability to control normal and
      smooth movement is Parkinson's disease.

PMID- 14977221
TI  - Three-dimensional point localisation in low-dose X-ray images using stereo
      photogrammetry.
AB  - A stereo-photogrammetric method for three-dimensional reconstruction of points in
      low-dose digital X-ray images obtained using a scanner with similar imaging
      geometry to that of computed tomography scan projection radiography, was
      analysed. A calibration frame containing 25 radio-opaque markers with known three
      dimensional locations was scanned, and the accuracy of reconstruction of the
      marker positions under varying control point configurations and separation angles
      was assessed. Errors of less than 1 mm were obtained when nine test points were
      reconstructed, with 16, 11 and 7 control points at a 90 degrees separation angle,
      and with 16 and 11 control points at 75 degrees and 60 degrees separation angles.
      The optimum reconstruction, with a resultant error of 0.68 mm, was found to occur
      at a separation angle of 90 degrees, with the largest number of control points
      (16) used to calculate the parameters of the transformation. Extrapolation in the
      scanning direction beyond the space defined by the control points gave errors of
      less than 2 mm. This method should be suitable for three-dimensional point
      reconstruction in applications such as cephalometry, brachytherapy planning and
      assessment of spinal shape.

PMID- 14977222
TI  - Experimental evaluation of lesion prediction modelling in the presence of
      cavitation bubbles: intended for high-intensity focused ultrasound prostate
      treatment.
AB  - The accuracy of high-intensity focused ultrasound (HIFU) lesion prediction
      modelling was evaluated for a truncated spherical transducer designed for
      prostate cancer treatment The modelling adapted the bio heat transfer equation
      (BHTE) to take into account the activity of cavitation bubbles generated during
      HIFU exposure. This modelling was used to predict the lesions produced by three
      different transducer geometries: fixed-focus, concentric-ring and 1.5D phased
      array. Lesions were predicted for different ultrasound exposure conditions close
      to those used in prostate cancer treatment. Twenty-one in vitro and nine in vitro
      experiments were performed on pig liver to validate the accuracy of the
      predictions. A good match was found between the predicted and experimental lesion
      shapes. Lesion dimensions (maximum depth and length, area at the centre of the
      lesion or central surface area) were measured on experimental and predicted
      lesions. The central surface area was predicted by the model with a range of
      error of 0.15-6.5% for in vitro tests and 0.97-9% in vivo. For comparison, BHTE
      without bubbles had a range of error of 0.4-55.5% (in vitro) and 9-25.5% (in
      vivo). The model should be accurate enough to predict HIFU lesions under
      ultrasound exposure conditions used in prostate cancer treatment.

PMID- 14977223
TI  - Patient-specific mechanical properties of a flexible multi-body model of the
      scoliotic spine.
AB  - The flexibility of the scoliotic spine is an important biomechanical parameter to
      take into account in the planning of surgical instrumentation. The objective of
      the paper was to develop a method to characterise in vivo the mechanical
      properties of the scoliotic spine using a flexible multi-body model. Vertebrae
      were represented as rigid bodies, and intervertebral elements were defined at
      every level using a spherical joint and three torsion springs. The initial
      mechanical properties of motion segments were defined from in vitro experimental
      data reported in the literature. They were adjusted using an optimisation
      algorithm to reduce the discrepancy between the simulated and the measured
      Ferguson angles in lateral bending of three spine segments (major or compensatory
      left thoracic, right thoracic and left lumbar scoliosis curves). The flexural
      rigidity of the spine segments was defined in three categories (flexible,
      nominal, rigid) according to the estimated mechanical factors (alpha). This
      approach was applied with ten scoliotic patients undergoing spinal correction.
      Personalisation of the model resulted in an increase of the initial flexural
      rigidity for seven of the ten lumbar segments (1.38 < or = alpha < or = 10.0) and
      four of the ten right thoracic segments (1.74 < or = alpha < or = 5.18). The
      adjustment of the mechanical parameters based on the lateral bending tests
      improved the model's ability to predict the spine shape change described by the
      Ferguson angles by up to 50%. The largest differences after personalisation were
      for the left lumbar segments in left bending (4 degrees +/- 3 degrees). The in
      vivo identification of the mechanical properties of the scoliotic spine will
      improve the ability of biomechanical models adequately to predict the surgical
      correction, which should help clinicians in the planning of surgical
      instrumentation manoeuvres.

PMID- 14977224
TI  - Tuned vibration absorber for suppression of rest tremor in Parkinson's disease.
AB  - A simple approach for the suppression of the tremor associated with Parkinson's
      disease is presented. The proposed system is a tuned vibration absorber (TVA),
      which has been very effective in the suppression of vibrations in an experimental
      model of the human arm with two degrees of freedom. Theoretical and numerical
      methods were used to study the behaviour of the arm model and to develop an
      effective tremor reduction approach. Based on these studies, a vibration absorber
      was designed, tested numerically and fabricated for experimental testing.
      Experimental investigations indicated that optimum control performance was
      related to the position of the controller and the excitation frequency. With a
      distance of 160 mm from the end of forearm, the TVA was found to have the best
      performance, and, for different tremor frequencies, the vibration of the
      experimental model was reduced by more than 80%.

PMID- 14977225
TI  - Feature selection of stabilometric parameters based on principal component
      analysis.
AB  - This study addresses the challenge of identifying the features of the Centre of
      pressure (COP) trajectory that are most sensitive to postural performance, with
      the aim of avoiding redundancy and allowing a straightforward interpretation of
      the results. Postural sway in 50 young, healthy subjects was measured by a force
      platform. Thirty-seven stabilometric parameters were computed from the one
      dimensional and two-dimensional COP time series. After normalisation to the
      relevant biomechanical factors, by means of multiple regression models, a feature
      selection process was performed based on principal component analysis. Results
      suggest that COP two-dimensional time series can be primarily characterised by
      four parameters, describing the size of the COP path over the support surface;
      the principal sway direction; and the shape and bandwidth of the power spectral
      density plot. COP one-dimensional time series (antero-posterior (AP) and medio
      lateral (ML)) can be characterised by six parameters describing COP dispersion
      along the AP direction; mean velocity along the ML and AP directions; the
      contrast between ML and AP regulatory activity; and two parameters describing the
      spectral characteristics of the COP along the AP direction. On the basis of the
      results obtained, some guidelines are suggested for the choice of stabilometric
      parameters to use, with the aim of promoting standardisation in quantitative
      posturography.

PMID- 14977226
TI  - Sympathetically induced spontaneous fluctuations of the photoplethysmographic
      signal.
AB  - The photoplethysmographic signal shows very low-frequency (VLF) spontaneous
      fluctuations that have been shown to be mediated by the sympathetic nervous
      system. In the current study, the photoplethysmographic signal was simultaneously
      measured in the two index fingers and the two second toes of 54 healthy male
      subjects. For each photoplethysmographic pulse, two parameters were derived: the
      pulse amplitude and its baseline, which are related to the arterial wall
      compliance and to the arterial blood volume, respectively. The baseline and the
      amplitude VLF fluctuations showed high right-left correlation both for hands
      (mean +/- SD 0.94 +/- 0.05 and 0.92 +/- 0.07, respectively) and for feet (0.90 +/
      0.08 and 0.89 +/- 0.07, respectively) that only slightly depended on the
      subject's age. Lower correlation was found between the hand and the foot (0.73 +/
      0.12 and 0.72 +/- 0.12 for the baseline and the amplitude, respectively). For
      each hand and foot the baseline and the amplitude VLF fluctuations were also
      correlated, with the baseline fluctuations lagging the amplitude fluctuations by
      3-20 pulses. The amplitude-baseline correlation and the standard deviation of the
      amplitude or the baseline divided by its mean significantly decreased with age.
      The VLF fluctuations of the photoplethysmographic parameters and the correlation
      coefficients between them provide better understanding of the autonomic nervous
      regulation of the blood circulation.

PMID- 14977227
TI  - Variability analysis of the respiratory volume based on non-linear prediction
      methods.
AB  - This work proposed and studied a method of automatically classifying respiratory
      volume signals as high or low variability by means of non-linear analysis of the
      respiratory volume. The analysis used volume signals generated by the respiratory
      system to construct a model of its dynamics and to estimate the quality of the
      predictions made with the model. Different methods of prediction evaluation,
      prediction horizons and embedding dimensions were also analysed. Assessment of
      the method was made using a database that contained 40 respiratory volume signals
      classified using clinical criteria into two classes: low or high variability. The
      results obtained using the method of surrogate data provided evidence of non
      linear determinism in the respiratory volume signals. A discriminant analysis
      carried out using non-linear prediction variables classified the respiratory
      volume signals with an accuracy of 95%.

PMID- 14977228
TI  - Detection of fast neuronal signals in the motor cortex from functional near
      infrared spectroscopy measurements using independent component analysis.
AB  - Fast changes, in the range of milliseconds, in the optical properties of cerebral
      tissue are associated with brain activity and can be detected using non-invasive
      near-infrared spectroscopy (NIRS). These changes are assumed to be caused by
      changes in the light scattering properties of the neuronal tissue. The aim of
      this study was to develop highly sensitive data analysis algorithms to detect
      this fast signal, which is small compared with other physiological signals. A
      frequency-domain tissue oximeter, whose laser diodes were intensity modulated at
      110 MHz, was used. The amplitude, mean intensity and phase of the modulated
      optical signal were measured at a sample rate of 96 Hz. The probe, consisting of
      four crossed source detector pairs was placed above the motor cortex,
      contralateral to the hand performing a tapping exercise consisting of alternating
      rest and tapping periods of 20 s each. An adaptive filter was used to remove the
      arterial pulsatility from the optical signals. Independent component analysis
      allowed further separation of a signal component containing the fast signal. In
      nine out of 14 subjects, a significant fast neuronal signal related to the finger
      tapping was found in the intensity signals. In the phase signals, indications of
      the fast signal were found in only two subjects.

PMID- 14977229
TI  - Linear interpolation error in measured surfaces in a dental erosion study.
AB  - An extensive palatal erosion study, which is currently being undertaken at the
      University of Dundee, aims to detect erosion through the precise mapping of
      replicas of children's incisors. All perceived sources of error are being
      scrutinised closely. The error due to the interpolation of surface positions from
      discrete point measurements has been investigated so that its contribution to the
      erosion estimates can be gauged. The calculation of the error statistics made use
      of covariance functions to express the undulation of the tooth surfaces. It has
      been found that, for the measurement point spacing of 150 microm being used in
      the current project, the interpolation error for an incisor is typically about 25
      microm, to be compared with the root-mean-square error due to tooth impression
      and replication procedures, assessed as being in the order of +/- 3 microm, and
      replica measurement, assessed as being in the order of +/- 5 microm. The
      interpolation error constitutes a surprisingly large proportion of the overall
      system error. The same error estimation technique can be applied usefully and
      without difficulty to other research studies concerning erosion or wear in
      natural or restorative dental surfaces.

PMID- 14977230
TI  - New method using multi-regression analysis on evoked electromyography during
      movement to adjust stimulation conditions.
AB  - A new method of stimulation of the lower extremities was devised that
      automatically adjusts the stimulation conditions at any angle of the knee joint.
      An M-wave is considered to indicate the stimulation conditions, because it is the
      waveform that results from direct stimulation to the axon of the alpha motor
      neuron. The present device adjusted the stimulation intensity, using multi
      regression analysis to evoke an M-wave of preset amplitude. Participants included
      five people without any neuromuscular impairment. The subjects sat on a chair
      during the test. The hip joint was fixed at a flexion angle of 90 degrees, and
      the ankle joint was fixed at the midposition. During passive knee joint movement
      ranging from 0 degrees to 135 degrees, M-waves were measured. Electrodes were
      attached at the popliteal fossa and the patella to stimulate the tibial nerve. Ag
      AgCl electrodes were put on the belly of the right soleus muscle for the M-wave
      measurement. The device was set to give M-waves close to the preset value, 10%
      Mmax. According to previous research, the allowable limit of M-wave amplitude
      deviations was reported to be about 5% Mmax. The M-wave amplitudes evoked by the
      device were in the allowable range (9.2 +/- 2.5% Mmax). The device enabled
      control of the M-wave amplitude over the entire range of motion of the joint.
      Using this device, it was possible to examine the excitability of the alpha motor
      neuron pool more precisely.

PMID- 14977231
TI  - Improved neuromonitoring during spinal surgery using double-train transcranial
      electrical stimulation.
AB  - Motor evoked potentials (MEPs) evoked by transcranial electrical stimulation
      (TES) have become an important technique for monitoring spinal cord function
      intra-operatively, but can fail in some patients. A new technique of double-train
      stimulation is described. A multipulse transcranial electrical stimulus is
      preceded by a preconditioning pulse train that leads to larger MEP responses. An
      MEP monitoring system was adapted for double-train transcranial stimulation
      (DTS). MEP responses from 160 anterior tibial muscles obtained by double-train
      stimulation were analysed. All patients received propofol/remifentanil/O2/N2O
      anaesthesia. Fifty-two (83%) out of 63 single-train tibial MEPs with response
      amplitudes below 100 microV were magnified to over 100 microV, with an inter
      train (inter-stimulus) interval ITI = 10-35 ms. These 63 amplitudes were
      magnified by an overall logarithmic mean factor of 15.5. For 97 MEPs with
      amplitudes above 100 microV, the logarithmic mean facilitation factor was 2.4. It
      was concluded that double-train TES stimulation can markedly facilitate responses
      to a single stimulus train (STS). The facilitation appears to be most effective
      when the responses to STS would otherwise be small or absent. This
      preconditioning stimulation technique is therefore useful when an STS leads to
      responses that are too small for effective monitoring.

PMID- 14977232
TI  - Comparison of spatial filter selectivity in surface myoelectric signal detection:
      influence of the volume conductor model.
AB  - Spatial filters are used for increasing selectivity in surface EMG signal
      detection. The study investigated the importance of the description of the volume
      conductor to the inference of conclusions on comparing filter selectivity from
      simulation analyses. A cylindrical multi-layer description of the volume
      conductor was used for the simulation analysis. Different anatomies were analysed
      with this model, and results on filter selectivity were compared. The
      longitudinal single (LSD), double (LDD) and normal double differential
      (Laplacian, NDD) filters were investigated. Largely different conclusions could
      be drawn when comparing filter selectivity resulting from simulations with
      different volume conductor models. A filter that performed best with a particular
      anatomy could be the poorest with another anatomy. With a bone-muscle model and
      superficial fibres, the ratio between peak-to-peak values of the propagating and
      non-propagating signal components was approximately 220% for LDD and LSD and
      lower than for NDD (approximately 290%). With a bone-muscle-fat-skin model, LSD
      performed significantly worse (150%) than both LDD and NDD, which showed similar
      performances (approximately 300%). Similarly, if the lateral distance of the
      recording was increased by 10 degrees, the signal amplitude was reduced to 2%
      with LSD and LDD and to 4% with NDD. With another anatomy, LSD and LDD reduced
      signal amplitude to 20-25%, and NDD reduced it to 4%. Similar considerations
      could be drawn for other selectivity indexes. Thus, modelling should be used
      carefully to infer conclusions on spatial selectivity and to indicate particular
      choices of spatial filters.

PMID- 14977233
TI  - Effect of accelerometer location on mechanomyogram variables during voluntary,
      constant-force contractions in three human muscles.
AB  - To understand better the features of the mechanomyogram (MMG) with different
      force levels and muscle architectures, the MMG signals detected at many points
      along three muscles were analysed by the application of a linear array of MMG
      sensors (up to eight) over the skin. MMG signals were recorded from the biceps
      brachii, tibialis anterior and upper trapezius muscles of the dominant side of
      ten healthy male subjects. The accelerometers were aligned along the direction of
      the muscle fibres. One accelerometer was located over the distal muscle
      innervation zone, and the other six or seven accelerometers were placed over the
      muscle, forming an array of sensors with fixed distances between them. The array
      covered almost the entire muscle length in all cases. MMG signals detected from
      adjacent accelerometers had similar shapes, with correlation coefficients ranging
      from about 0.5 to about 0.9. MMG amplitude and characteristic spectral
      frequencies significantly depended on accelerometer location. The MMG amplitude
      was maximum at the muscle belly for the biceps brachii and the tibialis anterior.
      Higher MMG characteristic spectral frequencies were associated with higher
      amplitudes in the case of the biceps brachii, whereas the opposite was observed
      for the tibialis anterior muscle. In the upper trapezius, the relationship
      between characteristic spectral frequencies, MMG amplitude and contraction force
      depended on the accelerometer location. This suggested that MMG spectral features
      do not only reflect the mechanical properties of the recruited muscle fibres but
      depend on muscle architecture and motor unit territorial distribution. It was
      concluded that the location of the accelerometer can have an influence on both
      amplitude and spectral MMG features, and this dependence should be considered
      when MMG signals are used for muscle assessment.

PMID- 14977234
TI  - Non-invasive estimation of myocardial infarction by means of a heart-model-based
      imaging approach: a simulation study.
AB  - In the study, a new myocardial infarction (MI) estimation method was developed
      for estimating MI in the three-dimensional myocardium by means of a heart-model
      based inverse approach. The site and size of MI are estimated from body surface
      electrocardiograms by minimising multiple objective functions of the measured
      body surface potential maps (BSPMs) and the heart-model-generated BSPMs. Computer
      simulations were conducted to evaluate the performance of the developed method,
      using a single-site MI and dual-site MI protocols. The simulation results show
      that, for the single-site MI, the averaged spatial distance (SD) between the
      weighting centres of the 'true' and estimated MIs, and the averaged relative
      error (RE) between the numbers of the 'true' and estimated infarcted units are
      3.0 +/- 0.6/3.6 +/- 0.6 mm and 0.11 +/- 0.02/0.14 +/- 0.02, respectively, when 5
      microV/10 microV Gaussian white noise was added to the body surface potentials.
      For the dual-site MI, the averaged SD between the weighting centres of the 'true'
      and estimated MIs, and the averaged RE between the numbers of the 'true' and
      estimated infarcted units are 3.8 +/- 0.7/3.9 +/- 0.7mm and 0.12 +/- 0.02/0.14 +/
      0.03, respectively, when 5 microV/10 microV Gaussian white noise was added to
      the body surface potentials. The simulation results suggest the feasibility of
      applying the heart-model-based imaging approach to the estimation of myocardial
      infarction from body surface potentials.

PMID- 14977235
TI  - Design of new titanium alloys for orthopaedic applications.
AB  - Parallel to the biofunctionalisation of existing materials, innovation in
      biomaterials engineering has led to the specific design of titanium alloys for
      medical applications. Studies of the biological behaviour of metallic elements
      have shown that the composition and structure of the material should be carefully
      tailored to minimise adverse body reactions and to enhance implant longevity,
      respectively. Consequently, interest has focused on a new family of titanium
      alloys: Ti-6Mo-3Fe-5Ta, Ti-4Mo-2Fe-5Ta and Ti-6Mo-3Fe-5Zr-5Hf alloys. The non
      toxicity of the specially designed titanium alloys compared with osteoblastic
      cells has been ascertained using MTT and RN tests. In addition, phase
      transformations upon thermal processing have been investigated, with comparison
      with a well-defined beta titanium alloy. Optimum thermal processing windows
      (above 550 degrees C) have been designed to generate a stable and nanostructured
      alpha phase from the isothermal omega phase that precipitates in a low
      temperature range (150-350 degrees C). The generation of such nanostructured
      microstructures should provide a promising opportunity to investigate tissue
      biomaterial interactions at the scale of biomolecules such as proteins.

PMID- 14977236
TI  - Estimation of the size of air emboli detectable by electrical impedance
      measurement.
AB  - Non-invasive detection of air emboli in blood is investigated in vitro using a
      tetrapolar electrical impedance measurement. A cubic tank with a linear array of
      four electrodes, spaced approximately 1 cm apart down one side, was filled with
      0.2 Sm(-1) saline. Bubbles were generated by carbon dioxide gas. Electrical
      transfer impedance was measured every 8.2 ms at 1.25 MHz. The movement of bubbles
      was recorded by a video camera, and their sizes and depths from the middle of the
      array were measured using captured video images. Changes in transfer impedance
      caused by passage of bubbles were clearly observed and almost identical with
      those calculated theoretically. Using lead field theory and experimental results,
      the fundamental limit on the detectable size of bubbles was estimated at the
      carotid artery, the great saphenous vein and the cephalic vein. The theoretical
      results showed that a 0.5 mm diameter bubble is detectable at a depth of 5.3 mm,
      similar to the depth of the great saphenous and the cephalic veins, and a 2.3 mm
      diameter bubble is detectable at a depth of 21 mm, similar to the depth of the
      common carotid artery.

PMID- 14977237
TI  - Interests and skills of volunteers in an ombudsman program: opportunities for
      participation.
AB  - Volunteers' reasons for interest in and skills they could employ as resident
      advocates in nursing facilities under the auspices of an ombudsman program were
      obtained from applications of 778 individuals. A unique feature of the research
      was that interests and skills were assessed prior to volunteer participation. In
      contrast to motivations for volunteering, skills of volunteers are infrequently
      studied; yet, they have implications for training and performance. Age,
      education, employment, and prior volunteer experience affected reasons for
      interest and skills. Less education, unemployment, older age, and fewer prior
      volunteer experiences may identify those with greater obstacles to participation
      who may benefit from additional education and training. Data from application
      forms may be used to suggest needed areas of instruction.

PMID- 14977238
TI  - Interrelations between subjective health and episodic memory change in Swedish
      and Canadian samples of older adults.
AB  - Recent research has documented associations between subjective health ratings and
      objective indicators of disease and death. Less is known about relations between
      subjective health ratings and level of cognitive performance in older adults. In
      this study, we explored whether subjective health ratings are related to episodic
      memory performance, both concurrently and across a three-year longitudinal
      interval. Persons aged 75-84 years, and participating in the Swedish Kungsholmen
      Project (n = 105) or the Canadian Victoria Longitudinal Study (n = 71), were
      examined. Results showed that in both samples, while the cross-sectional
      relationship was non-significant, longitudinal change in perceptions of
      subjective health were related to change in episodic memory performance. Next,
      the two samples were combined in additional analyses. Here, results further
      revealed that the associations between longitudinal change in subjective health
      and memory performance generalized across samples independently of demographic,
      changing physical health status, and subjective memory decline differences. Thus,
      the present findings suggest that subjective health may be added to the growing
      number of individual-difference variables that are predictive of episodic memory
      change in very old age.

PMID- 14977239
TI  - Implications of non-response of older women to a short form of the Center for
      Epidemiologic Studies Depression Scale.
AB  - The Center for Epidemiologic Studies Depression Scale (CES-D) is frequently used
      in epidemiological surveys to screen for depression, especially among older
      adults. This article addresses the problem of non-completion of a short form of
      the CES-D (CESD-10) in a mailed survey of 73- to 78-year-old women enrolled in
      the Australian Longitudinal Study on Women's Health. Completers of the CESD-10
      had more education, found it easier to manage on available income and reported
      better physical and mental health. The Medical Outcomes Study Short Form Health
      Survey (SF-36) scores for non-completers were intermediate between those for
      women classified as depressed and not depressed using the CESD-10. Indicators of
      depression had an inverted U-shaped relationship with the number of missing CESD
      10 items and were most frequent for women with two to seven items missing. Future
      research should pay particular attention to the level of missing data in
      depression scales and report its potential impact on estimates of depression.

PMID- 14977240
TI  - Life-span learning: a developmental perspective.
AB  - The article discusses learning as embedded processes of development and aging,
      and as social activity over the life course. The concept of life-span learning is
      proposed and outlined to discuss these processes as aspects of and propositions
      in life-span development and aging theory. Life-span learning processes arise and
      continuously develop in a dynamically complex body, brain, and the mind they
      support as essential features of development and aging over the life course. Life
      span learning processes are established by evolutionary adaptive mechanisms,
      enriched by challenging environments, and continuously developed in supportive
      social structures. These ideas are derived from evolutionary biology and
      psychology, the cognitive sciences, life-span development and aging research, and
      adult development and learning studies. It is argued that life-span learning
      activities that challenge the body-mind-brain nexus are indispensable to optimize
      individual development and aging. Three global interventions and their strategies
      are discussed that enhance life-span learning: Learning to Learn, Learning for
      Growth, and Learning for Well-being.

PMID- 14977241
TI  - Aging in place: knowing where you are.
AB  - Research on aging in place appropriately emphasizes the value of familiar
      surroundings. The current study contributes an exploration of elders' personal
      knowledge of where and with whom they are aging in place, knowledge actively
      accumulated from a lifetime spent in the same area. Structured conversations over
      a four-month period with 10 elders living on a peninsula in northern Maine
      provide richly detailed narratives of physical and social particulars of where
      they live. I use Rowles's (1978) image of concentric circles radiating out from
      home to organize the information gathered regarding each elder's dwelling,
      neighborhood and community. Most notable is the depth and detail of their
      personal knowledge of where they are and with whom they are growing old. I
      conclude that both the knowledge itself, and the sharing of that knowledge with
      others, contribute to the implicit and explicit support deemed so valuable for
      elders who age in place.

PMID- 14977242
TI  - Personality traits and stress sensitivity in migraine patients.
AB  - A review of the literature on migraine and personality yielded strong evidence
      for secondary neuroticism and increased sensitivity to stress in patients with
      migraine. This study focused on the identification of specific stressful
      situations and coping strategies in such patients. We conducted a
      psychodiagnostic study of 30 migraine patients in accordance with the criteria of
      the Headache Classification Committee of the International Headache Society and
      30 healthy control subjects matched for age, sex, and social status. All
      participants completed the Minnesota Multiphasic Personality Inventory (MMPI) and
      special questionnaires on stressful situations and coping strategies. The
      migraine patients had higher neuroticism and introversion scores on the MMPI than
      the healthy subjects. There was a positive correlation between the neuroticism
      score and headache duration (number of hours per week). The patients used coping
      strategies characterized by the development of physical symptoms, social
      isolation, and preoccupation with stress. They rated themselves as less calm,
      less capable of relaxing, and more irritable than did the healthy controls
      subjects, and they responded more often with internal tension, especially in work
      and other achievement situations. Questionnaires that measure constructs dealing
      with stress yield information that is more relevant for the treatment of
      migraines than do global personality tests.

PMID- 14977243
TI  - Listening to mozart reduces allergic skin wheal responses and in vitro allergen
      specific IgE production in atopic dermatitis patients with latex allergy.
AB  - In atopic dermatitis patients with latex allergy, listening to Mozart reduced
      skin wheal responses induced by latex, but not by histamine, whereas listening to
      Beethoven failed to produce similar results. Listening to Mozart also decreased
      in vitro total IgE and latex-specific IgE production with concomitant skewing of
      the cytokine pattern toward the Th1 type, that is, an increase in Th1 cytokine
      production and decrease in Th2 cytokine production by peripheral blood
      mononuclear cells, whereas listening to Beethoven failed to do so. These results
      suggest that therapy using specific types of music may be an effective treatment
      of allergic diseases.

PMID- 14977244
TI  - Effects of life-event stress and hardiness on peripheral vision in a real-life
      stress situation.
AB  - Previous research has only examined perceptual deficits that are hypothesized in
      a model of stress and injury under laboratory-induced stress conditions. The
      generalizability of findings from such induced-stress conditions is limited
      beyond the laboratory. The current research examined the influence of life-event
      stress and hardiness on peripheral narrowing in a real-life stress situation.
      Athletes completed life-stress and hardiness questionnaires, along with measures
      of state anxiety and peripheral vision. The stress condition was obtained by
      assessing the athletes within 2 hours of a competition. The real-life stress
      condition had a larger effect on state anxiety and peripheral narrowing than the
      laboratory-induced situations used in previous research, with effect sizes twice
      and three times as large as those reported in the literature. All athletes
      experienced significant reductions in peripheral vision prior to competition,
      regardless of life-event stress or hardiness levels.

PMID- 14977245
TI  - Blood pressure regulation, cognition, and depression in response to orthostatic
      challenge in African American children: an initial investigation.
AB  - Poor blood pressure regulation (BPR) in response to orthostasis could contribute
      to cerebral hypoperfusion and cell damage. The authors of this study examined
      neuropsychological function and mood in relation to BPR following orthostatic
      challenge in African American children, aged 6 to 9 years. Participants (N = 33)
      laid supine for 5 minutes, before having their BP taken. Participants then stood
      and had BP measured again at 1, 3, and 5 minutes. After a rest, the authors
      administrated neuropsychological and depression tests while the participants were
      seated. The authors calculated the difference between supine and 1-minute
      standing systolic blood pressure (SBP) and pulse pressure (PP) scores. In
      response to orthostatic challenge, smaller increases in SBP were predictive of
      decreased verbal memory whereas smaller increases in PP were associated with
      increased depressive symptomatology and poor prospective memory. In conclusion,
      less effective BPR was associated with increased depression and poor performance
      on some neuropsychological tests.

PMID- 14977246
TI  - The parent-adolescent relationship education (PARE) program: a curriculum for
      prevention of STDs and pregnancy in middle school youth.
AB  - The Parent-Adolescent Relationship Education (PARE) Program, designed for parents
      and middle school students, focuses on strengthening family communication about
      sexual issues and behaviors to help prevent teen pregnancy, human
      immunodeficiency virus (HIV), and other sexually transmitted diseases (STDs). The
      program includes content about reproduction, STDs and Acquired Immune Deficiency
      Syndrome (AIDS), contraception, sex risks, and safe-sex behaviors. The course
      uses social learning and cognitive behavioral concepts to enhance decision
      making, refusal, and resistance skills. A randomized treatment or control group
      design is used to assign parent-child dyads to an experimental education group
      (social learning) or an attention-control group (traditional didactic teaching).
      Three post-program maintenance or booster sessions are held at 6-month intervals
      and at times prior to peak teen conception periods to reinforce the knowledge and
      skills learned. Pre- and posttests for parents and students assess group
      differences in parental involvement and communication, contraception, sex
      attitudes and intentions, sex behaviors (initiation of sexual intercourse,
      frequency, number of partners, contraceptive practices, refusal skills), and the
      incidence of pregnancy.

PMID- 14977247
TI  - Spatial patterns of the pathological changes in the cerebellar cortex in sporadic
      Creutzfeldt-Jakob disease (sCJD).
AB  - The spatial patterns of the vacuolation ("spongiform change"), surviving cells,
      and prion protein (PrP) deposition were studied in the various cell laminae of
      the cerebellar cortex in 11 cases of sporadic Creutzfeldt-Jakob disease (sCJD).
      Clustering of the histological features, with the clusters regularly distributed
      along the folia, was evident in all cell laminae. In the molecular layer,
      clusters of vacuoles coincided with the surviving Purkinje cells. In the granule
      cell layer, however, the spatial relationship between the vacuoles and surviving
      cells was more complex and varied between cases. PrP deposition was not spatially
      correlated with either the vacuoles or the surviving cells in any of the
      cerebellar laminae in the majority of cases. In some cases, there were spatial
      relationships between the histological features in the molecular and granule cell
      layers. The data suggest that degeneration of the cerebellar cortex in sCJD may
      occur in a topographic pattern consistent with the spread of prion pathology
      along anatomical pathways. The development of the vacuolation may be an early
      stage of the pathology in the cerebellum preceding the appearance of the PrP
      deposits. In addition, there is evidence that the pathological changes may spread
      across the different laminae of the cerebellar cortex.

PMID- 14977248
TI  - Loss of chromosome 22 and proliferative potential in ependymomas.
AB  - Fluorescence in situ hybridisation (FISH) analysis using total chromosome 22
      painting and locus specific 22q11.2 (bcr locus) probes was performed on sections
      from archival paraffin-embedded tumours obtained from 28 patients diagnosed with
      either ependymoma, WHO grade 11 (18 cases) or anaplastic ependymoma, WHO grade
      111 (10 cases). The Ki-67 labelling index (LI) analysis was carried out in
      parallel to estimate the tumours' proliferative potential. Loss of chromosome 22
      was revealed in eleven (39%) ependymomas, seven (39%) WHO grade II and four (40%)
      anaplastic variants. Concurrent cytogenetic analysis was performed on 11 tumours
      to confirm the loss of chromosome 22 in four cases; clones with a loss of
      chromosome 22, which was identified by FISH, were not detected by standard
      cytogenetics in two samples. The loss of chromosome 22 was restricted either to
      the tumours' site or to sex or age of the patients studied. The Ki-67 LI ranged
      from 0.1 to 32.0% (mean 4.3%). Low-grade tumours significantly showed a lower
      mean Ki-67 LI than those classified as anaplastic tumours (3.1% and 6.4%,
      respectively). Additionally, the mean Ki-67 LI for ependymomas with a loss of
      chromosome 22 was significantly lower than that for tumours with chromosome 22
      disomy (1.6% and 6.0%, respectively, p = 0.05), indicating that loss of
      chromosome 22 may be associated with the subset of ependymomas characterised by
      low proliferative capacities.

PMID- 14977249
TI  - Degenerative axonal changes in the hippocampus and amygdala in Parkinson's
      disease.
AB  - The morphological background of cognitive and emotional impairments in
      Parkinson's disease (PD) has not yet been fully explained. We evaluated the
      expression of synaptic proteins: alpha- and beta-synuclein, synaptophysin and
      synaptobrevin and ultrastructural changes of perikaryons and axons in limbic
      structures at post-mortem from cases of PD to estimate degenerative axonal
      pathology in the hippocampus and amygdala [corrected]. Limbic structures
      (enthorinal cortex, hippocampus, and amygdala) are essential for the cognitive
      processes and emotional behaviour. We found that presynaptic axon pathology is
      mostly connected with hippocampal CA2-3 and dentate hilar regions as well as with
      the cortical and medio-central complexes of amygdala. Heterogeneous
      immunoreactivity of alpha-synuclein and diversified ultrastructure of Lewy bodies
      (LBs) and Lewy neurites (LNs) indicate their consecutive developmental stages. We
      observed an excessive perineuroneal expression of synaptophysin in the dentate
      hilar region in all PD cases, except one. This suggests that the dysfunction of
      synapses in this region may result from axonal pathology. Our study indicates a
      relation between cognitive and behavioural symptomatology in PD and alpha
      synuclein dependent axonal pathology in the hippocampus and amygdala.

PMID- 14977250
TI  - Morphology of pineal glands in human foetuses and infants with brain lesions.
AB  - The pineal gland is an organ involved in regulation of homeostasis and body
      rhythms. It plays an important role in the growth foetuses and adaptation of
      newborns to new environmental conditions. The requirements of foetuses and
      newborns progressively change during development. The purpose of the study was to
      evaluate morphological changes of pineal glands in foetuses and infants with
      brain lesions. The results of our study showed that parenchyma of developing
      pineal glands was susceptible to injury in most autopsied foetal and infantile
      cases. Morphological changes in pineal glands were found in 90% of autopsied
      brains but 100% of the cases had infections. The lesions in the pineal included
      mainly haemorrhagic, necrotic and cystic changes. In our autopsied foetuses and
      children, morphological changes in pineal glands were concomitant with various
      lesions of brain parenchyma. All results of our study lead to the conclusion that
      the pineal gland during its development is very susceptible to injury. The
      failure of normal pineal gland development and subsequent impaired production of
      melatonin decrease resistance of newborns and children to various environmental
      harmful agents.

PMID- 14977251
TI  - Neuronal heterotopies and formation of cortical anomalies.
AB  - The history of neuronal disturbances of a group of cases was examined
      neuropathologically. The correlation between three consecutive occurrences of
      migration and the observed changes made it possible to establish all the modes of
      this process in six cases. In spite of this process, a relatively long survival
      of six years was observed. A much longer survival of 45 years was observed in
      case where anomalies of the second mode of neuronal migration did not occur.

PMID- 14977252
TI  - Surgical treatment of brainstem tumours with special emphasis on the operative
      approach through the fourth ventricle floor.
AB  - Over the last 25 years there have been reports from the widely recognised
      neurosurgical centres on the positive clinical results of partial and even
      complete removal of brainstem tumours. They confirmed relatively high incidence
      of benign tumours like low-grade gliomas and haemangioblastomas in this region.
      Based on imaging studies (MRI) and surgical experiences, brainstem tumours can be
      divided into focal and diffuse. Focal lesions are amenable to surgery;
      particularly, those with a prominent exophytic portion. Open surgery remains
      controversial in pure intrinsic brainstem tumours as the surgical approach itself
      may lead to serious postoperative complications. Different approaches (including
      the most frequent one--through the fourth ventricle floor) are used depending on
      the tumour location. As minimal invasiveness is mandatory during transtegmental
      route safe approach zones within the rhomboid fossa were defined morphologically
      and morphometrically--suprafacial and infrafacial (i.e., situated above and below
      facial colliculus, respectively). Application of the proposed minimal invasive
      surgical approach through the fourth ventricle floor should reduce postoperative
      morbidity and mortality in patients with tumours in pons and upper medulla
      oblongata treated surgically.

PMID- 14977253
TI  - Primary posterior fossa tumours in adult patients.
AB  - Surgery within posterior fossa tumours aided by modern imaging techniques,
      operating microscope and surgical technique, has progressed rapidly. In fact,
      operations once impossible to perform safely are now routine. Current surgical
      techniques are also leading to more complete tumour resections, thereby
      prolonging survival times and, for benign tumours, lowering recurrence rates.
      Regardless of the quality of technological advances, excellent results are still
      primarily dependent on a highly skilled neurosurgical team as well as on a
      special neurosurgical intensive care unit. Complications, although never totally
      avoided, are by far better prevented than treated. That prevention starts with
      the preoperative evaluation and continues well into the period of postoperative
      care.

PMID- 14977254
TI  - Correlation of facial nerve paresis and histopathological type of vestibular
      schwannoma.
AB  - The objective of the study was to evaluate the dependence of facial nerve
      paresis, as a symptom of cerebellopontine angle tumour, on the histopathological
      subtype of vestibular schwannoma, diagnosed from a post-operative
      histopathological examination. We retrospectively analysed 91 surgically treated
      patients with vestibular schwannoma. We studied the histopathological subtype and
      the preoperative condition of the facial nerve. The following WHO 2000 subtypes
      were distinguished: neurinoma cellular (51 cases), neurinoma conventional (23
      cases), neurinoma ancient (11 cases), (other types: 2 neurofibroma and 2
      ganglioneuroma). We analysed the dependence of facial nerve paresis on the
      histological subtype of tumours and their sizes. The analysis was based on the
      traditional classification: Antoni A (11 cases), Antoni B (12 cases) Antoni A/B
      (23 cases) and Antoni B/A (40 cases). 30 patients (30%) in the analysed group had
      paresis of the facial nerve preoperatively. Preoperative facial paresis occurred
      frequently in subtypes "cellular" and Antoni B, and rarely in subtypes
      conventional and Antoni A and B/A. In the small tumour cases (up to 20 mm),
      facial nerve paresis occurred frequently in subtypes cellular and conventional,
      as well as in Antoni A and A/B.

PMID- 14977255
TI  - Stereotactic methods in interdisciplinary diagnosis and treatment of posterior
      fossa tumours.
AB  - For over 2 years, we have had access to latest generation apparatus and software
      for planning and stereotactic treatment as well as for x-rays treatment. Until
      now, we have carried out over 100 procedures. These included 52 stereotactic
      biopsies of neoplasms, some of them located within the structures of the
      posterior fossa. In this report, we have discussed the possibilities and
      effectiveness of diagnosis and treatment of tumours located in different
      structures, including posterior cave. In the study, we used stereotactic methods.
      We have described biopsies of the following tumours: cerebellar hemisphere tumour
      (diagnosed as "metastatic atypic planoepitheliale carcinoma" in a patient with
      coexisting orbit lymphoma), a bifocal lesion (located in cerebellar hemisphere
      and cerebellar peduncle, diagnosed as pilocytic astrocytoma of WHO malignancy
      grade II/III), and lesion (located in the pons, diagnosed as pilocytic
      astrocytoma WHO grade II).

PMID- 14977256
TI  - Haemangioblastoma of the posterior cranial fossa: clinico-neuropathological
      study.
AB  - Haemangioblastoma (HBs) may occur sporadically in the central nervous system, or
      in association with von Hippel-Lindau (VHL) disease. Haemangioblastoma of the
      central nervous system is often seen in the posterior cranial fossa. VHL is an
      autosomaly dominant disorder. In sporadic HBs tumours, VHL alleles are reported
      to be inactive in up to 50% of tumours. Five patients with tumours of the
      posterior cranial fossa were examined by scyntygrapghy, computed tomography or
      magnetic resonance imaging (MRI). Metastases were initially diagnosed by
      neuroimaging examinations in two patients, and HBs in the remaining cases. In
      four patients, tumours were removed neurosurgically. Two patients had evidence of
      VHL disease. All resected tumours and autopsy materials were studied
      histologically and immunohistologically. Most antibodies that were used showed
      positive immunoreactions with stromal, endothelial, and pericyte or macrophage
      cells in tumours diagnosed as haemangioblastoma. Preoperative diagnosis of
      haemangioblastoma is mostly precise with MRI or magnetic resonance angiograghy.
      The surgical treatment of HBs is only a part of the complex therapeutical
      process. Diagnosis based on the gene analysis can be very useful in early
      detection or protection against potential recurrence of this disease in patients
      and their families.

PMID- 14977257
TI  - Posterior fossa tumours in children and adolescents. A clinicopathological study
      of 216 cases.
AB  - Posterior fossa tumours are characteristics of paediatric population. This report
      is a study of 216 consecutive cases of neuropathologically verified brain tumours
      in children under the 18th year of age, who underwent surgery at the Polish
      Mother Memorial Hospital in Lodz, Poland, between 1990 and 2003. Children with
      posterior fossa tumours constituted 47% of all paediatric patients with brain
      tumours. Male-to-female ratio was 1.35:1, and the major peak in the incidence of
      tumours was observed between 4 and 6 years of age. The most common locations were
      the cerebellum along with the fourth ventricle (61.5%), cerebellar hemispheres
      (27.5%), and brain stem (7.5%). Astrocytic tumours (predominantly pilocytic
      astrocytomas) were the most common group of neoplasms (41.5%) followed by
      embryonal tumours (all but one medulloblastomas--34.5%), ependymal tumours (13%),
      and mixed neuronal-glial tumours (5.5%). Altogether, nineteen histological types
      of brain tumours were diagnosed in the analysed population. The location of
      tumours, age and sex were compared with those of previously published series of
      paediatric posterior fossa tumours.

PMID- 14977258
TI  - Notes from the end.

PMID- 14977259
TI  - Minnesota excels in end-of-life care.

PMID- 14977260
TI  - Educating undertakers.

PMID- 14977261
TI  - Talking to patients about end-of-life care.

PMID- 14977262
TI  - "We have met the enemy..." part two, or On the disadvantages of hanging
      separately.

PMID- 14977263
TI  - Full of life.

PMID- 14977264
TI  - Laying the body to rest.

PMID- 14977265
TI  - After Death Care at North Memorial.

PMID- 14977266
TI  - Writing an ethical will.

PMID- 14977267
TI  - Notes from a rural Minnesota coroner.

PMID- 14977268
TI  - Attending a patient's funeral.

PMID- 14977269
TI  - Excerpts from "The natural right to a natural death". 1899 [classical article].

PMID- 14977270
TI  - Completing a death certificate properly.

PMID- 14977271
TI  - Coding palliative care.

PMID- 14977272
TI  - Enhanced pregnancy-associated mortality surveillance: Minnesota, 1990-1999.
AB  - Comprehensive surveillance is critical to accurate identification of pregnancy
      associated deaths and risk factors and is the first step in implementing programs
      to prevent such deaths in young women. In Minnesota, surveillance is currently
      based on analysis of data from death records. This study sought to demonstrate
      that the state's current surveillance method underestimates the actual burden of
      maternal deaths in Minnesota. It proposes that ongoing enhanced surveillance-
      analysis of death certificate data combined with the linking of death records of
      women of reproductive age with live birth records or fetal death records-
      provides a more complete and accurate accounting of pregnancy-associated
      mortality in Minnesota.

PMID- 14977273
TI  - Healthcare solutions for black Americans.

PMID- 14977274
TI  - The phoenix has risen but has failed to thrive: hope on the horizon for King-Drew
      Medical Center.

PMID- 14977275
TI  - Age 14 starts a child's increased risk of major knife or gun injury in
      Washington, DC.
AB  - This retrospective review of eight years of trauma registry data at an inner-city
      level-1 trauma center was undertaken to discover at what age urban children start
      to become at high risk of being victims of either a major gunshot wound or
      stabbing. We reviewed data from 2,191 patients who were the victim of either a
      gunshot wound or stabbing, were 18 years of age or under, and met pre-established
      criteria to qualify as a major trauma victim. There was a rise and subsequent
      fall in both overall crime and intentional injury rates during the eight-year
      period. Nevertheless, in each of the eight years studied, the risk of being a
      victim of a major gunshot wound or stabbing rose abruptly at age 14 (p<0.01) and
      the incidence continued to rise sharply through age 18.

PMID- 14977276
TI  - Knowledge, behaviors, and attitudes about hearing loss and hearing protection
      among racial/ethnically diverse young adults.
AB  - Over 11 million individuals exhibit some degree of permanent noise induced
      hearing loss (NIHL). Despite such data, there remains a paucity of empirical
      evidence on the knowledge of noise exposure and hearing protection devices (HPDs)
      for young adults, particularly those of diverse racial/ethnic backgrounds. This
      lack of research is unfortunate, as prior research suggests that the incidence of
      NIHL can be reduced through educational programs, such as hearing conservation
      programs (HCPs). Moreover, research also indicates that such educational programs
      are more beneficial when developed for specific age and/or ethnic/racial groups.
      The primary aim of this investigation was to determine the knowledge base of 200
      college-aged young adults aged 18-29, concerning the auditory mechanism, NIHL,
      and the use of HPDs. The second aim of this study was to identify race and
      ethnicity differences or similarities in knowledge of these areas among African
      American and caucasian young adults. Overall, in many instances, a majority of
      the young adults in our study demonstrated a high degree of knowledge concerning
      factors associated with exposure to excessive noise and the risk of hearing loss.
      Yet, the results also revealed significant racial/ethnic differences in
      knowledge, behaviors, and attitudes about the use of HPDs. Recent estimates
      suggest that more than 11 million individuals in the United States exhibit some
      degree of NIHL. Moreover, 40 million individuals work in environments that
      contain potentially harmful noise levels, and over 50 million Americans routinely
      use firearms--a common cause of noise-induced hearing impairment. A specific
      hallmark manifestation of NIHL is a permanent decrease in hearing sensitivity
      from 3,000-6,000 Hz, with a characteristic notch at 4,000 Hz. Additional effects
      of exposure to high noise levels include physiological changes in heart rate and
      blood pressure, decrease in work productivity, and an interference with
      communication that results from the masking of speech. With these considerations
      in mind, the purpose of this study was to investigate the knowledge, behaviors,
      and attitudes of a young-adult population in the United States concerning the
      factors that contribute to NIHL and the use of hearing protection. Additionally,
      this study was interested in whether there were racial/ethnic differences or
      similarities in knowledge of hearing loss and the use of HPDs among African
      American and caucasian young adults.

PMID- 14977277
TI  - Maternal support in the delivery room and birthweight among African-American
      women.
AB  - OBJECTIVES: We performed a hospital-based case control study of African-American
      mothers to explore the relationship between maternal support by a significant
      other in the delivery room and very low birthweight (VLBW). METHODS: We
      administered a structured questionnaire to mothers of VLBW (less than 1,500 g;
      N=104) and normal birthweight (greater or equal to 2,500 g; N=208) infants.
      RESULTS: The odds ratio for VLBW comparing women without social support in the
      delivery room to those with a companion was 3.5 (2.1-5.8). Several traditional
      risk factors were not associated with VLBW, but older maternal age and perceived
      racial discrimination were. CONCLUSIONS: Maternal support in the delivery room or
      factors closely associated with it significantly decreases the odds of delivering
      a VLBW infant for African-American women.

PMID- 14977278
TI  - Doxorubicin cardiotoxicity in African Americans.
AB  - PURPOSE: The African-American race was examined as a risk factor for
      cardiotoxicity from doxorubicin-based therapy for cancer. PATIENTS AND METHODS:
      Retrospective survey of the Howard University Hospital cancer registry during
      1997-2001 identified 100 evaluable patients out of 120 African Americans who
      underwent doxorubicin-based combination chemotherapy (65% women, 35% men, median
      age 46 years, range 32-84 years). The fraction of patients who developed post
      treatment cardiotoxicity, defined as congestive heart failure or a left
      ventricular ejection fraction less than 45%, was compared with that from a
      retrospective study of 399 patients of unknown age and racial distribution. Cases
      were stratified by cumulative dose of doxorubicin. Statistical significance of
      the difference in incidence of cardiotoxicity was tested by chi-square analysis.
      RESULTS: Patients received multiple doses of doxorubicin (range 264 to 580 mg/m2
      with median of 374) with the final echocardiographic assessment at a median of
      1.3 years. Howard oncologists frequently used a 48-hour infusion rather than the
      conventional rapid bolus to reduce the cardiotoxicity of doxorubicin. The
      fraction with cardiotoxicity in our study versus Lefrak's review at four ranges
      of doxorubicin was 25% versus 18% at 551-600 mg/m2, 10% versus 4% at 501-550
      mg/m2, 4% versus 1% at 451-500 mg/m2, and 0% versus <1% at <450 mg/m2. Seventy
      two percent of the patients having depressed ejection fraction and/or heart
      failure were women. African Americans had a higher rate of cardiotoxicity after
      doxorubicin (7/100 cases) than that of Lefrak's (10/399) study population and
      were statistically significant at p<0.027 with an odds ratio of 2.93. CONCLUSION:
      We have shown for the first time that African Americans at our institution appear
      to suffer cardiotoxicity from doxorubicin three times more frequently than the
      previously noted study population. To better clarify this observation, a larger
      study in a multiracial setting is needed.

PMID- 14977279
TI  - Prevalence and correlates of initiation of smoking behavior among preteen black
      and white children.
AB  - This study estimated smoking prevalence and identified factors associated with
      initiation among preteens in Nashville, TN. An anonymous, self-administrated
      questionnaire was given to 238 fifth- and sixth-graders in a middle-class
      neighborhood school. The mean age at initiation was 8.5 years (range 6-11 years).
      Overall, 10.5% of students had ever smoked; 16.1% of blacks and 9.3% of whites.
      Eighty-six percent continued to smoke. Black sixth-graders smoked (26.9%) four
      times the rate of black fifth-graders and 2.5 times that of white sixth-graders.
      Relatives initiated 78% of blacks while friends initiated 68% of whites. One
      quarter of smokers got their cigarettes at home. Regular attendees of religious
      services had a lower smoking rate (6.9% versus 16.4%; p=0.01). Smoking rates
      decreased with increased knowledge of risks (p=0.00001). Among smokers, none
      believed that smoking is a risk factor for heart disease, 96% did not believe
      that smoking has any short-term health effects or is a risk factor for stroke.
      Few ever-smokers had a complete understanding of the health risks. Targeted
      messages and curriculum should be developed to teach preteens about the short-
      and long-term dangers of smoking. Clinicians can play a major role in educating
      their clients about the risks of smoking.

PMID- 14977280
TI  - Harris-Benedict equations do not adequately predict energy requirements in
      elderly hospitalized African Americans.
AB  - BACKGROUND: Malnutrition, associated with poor outcome in the elderly, may be
      exacerbated by weight loss during hospitalization. Accurate estimation of energy
      requirements is important, particularly if predictions are applied to caloric
      supply. Because data on energy requirements for the elderly are limited,
      particularly for African-American patients, predictions are commonly made with
      equations derived from a younger, caucasian, cohort from 80 years ago. METHOD: To
      compare measured resting metabolic rate (RMR) in a hospitalized elderly African
      American cohort in an urban community hospital during 1998 with Harris-Benedict
      predictions of basal energy expenditure (BEE). Energy expenditure was measured by
      a strict protocol with a portable metabolic cart, and height and weight were
      measured standardly and used to calculate BEE and body mass index (BMI). RESULTS:
      In 61 subjects, aged 79.6+/-8.9 years, measured RMR was significantly greater
      than predicted BEE (p=0.001, t-test). Caloric expenditure averaged 24.7+/-5
      kcal/kg/day, but the range was broad (14-39 kcal/kg/day). The BEE prediction was
      20.3+/-2.4 kcal/kg/day. CONCLUSION: In elderly hospitalized African-American
      patients, the Harris-Benedict equation significantly underestimated energy
      requirements. Given the link between unintentional weight loss and increased
      mortality on the one hand and potential clinical complications of overfeeding on
      the other, measurement of energy expenditure is warranted.

PMID- 14977281
TI  - Racial disparities in sexual risk behaviors and drug use among older gay/bisexual
      and heterosexual men living with HIV/AIDS.
AB  - Adults over age 50 comprise 11% of yearly AIDS cases, yet little is known about
      their sexual risk behaviors and drug use following diagnosis with HIV/AIDS. The
      present questionnaire study examines potential racial differences in sexual risk
      and drug use behaviors among 59 HIV-infected gay/bisexual and heterosexual men
      over age 50 who were recruited from HIV-related organizations in New York City
      between 1996-1998. The majority (59%) of older men reported unprotected sex since
      diagnosis, and 36% had done so in the past six months. African-American
      gay/bisexual men (n=12) were significantly more likely than white gay/bisexual
      men (n=32) to report unprotected vaginal/anal sex in the past six months (67%
      versus 22%, p<0.01), since diagnosis (42% versus 9%, p<0.05), and to report a
      history of intravenous drug use (50% versus 3%, p<0.01), but did not differ from
      heterosexual African-American men (n=15). No differences were found in reports of
      unprotected oral sex or recent use of hard drugs (i.e., crack, cocaine, heroin).
      These findings suggest that interventions targeting older African-American men
      (both gay/bisexual and heterosexual) with HIV/AIDS are needed to reduce risk
      behaviors and prevent HIV transmission in this population.

PMID- 14977282
TI  - Hemoglobinopathy and pattern of musculoskeletal infection in children.
AB  - BACKGROUND: The bacterial pathogens associated with osteomyelitis in patients
      with hemoglobinopathy (HbSS) are controversial. There is insufficient data on the
      common musculoskeletal (MSS) infections in patients with hemoglobinopathies and
      the associated bacterial pathogens in Nigeria. OBJECTIVES: To identify the common
      MSS infections in children and the associated bacterial pathogens, especially in
      those with abnormal hemoglobin genotypes. METHODS: A retrospective case review
      was done of pediatric and adolescent patients admitted with bone and soft tissue
      infections over a seven-year period in a Nigerian teaching hospital. RESULTS: One
      hundred-nineteen patients were studied, with mean age 7.9+/-5.6 years and male
      female ratio of 1.3:1. Out of 78 patients with known genotype, 62.8% had HbAA,
      20.5% HbSS, 9% HbAS, and 7.7% HbAC. The most common MSS infections were
      osteomyelitis (64.7%), pyomyositis (17.6%), and septic arthritis (10.1%). Others
      were cellulitis (5.9%), tuberculous arthritis (0.8%), and necrotizing fasciitis
      (0.8%). Staphylococcus aureus (S. aureus) was isolated from 62% of chronic
      osteomyelitis (COM) and 58% of pyomyositis, while gram-negative bacilli accounted
      for 34% and 42%, respectively. S. aureus was isolated from 63% of patients with
      HbAA, 40% with HbSS, 58% with HbAS, and 58% with HbAC, while gram-negative
      bacilli accounted for 33%, 60%, 33%, and 33%, respectively. Osteomyelitis and
      pyomyositis appear to be similarly common in patients with and without HbSS (RR
      1.29; 95% CI 0.47-3.50). Osteomyelitis and soft tissue infections in general also
      appear to be equally common in them (RR 1.16; 95% CI 0.39-4.11). However,
      osteomyelitis appears to be more common among patients with HbSS than those with
      HbAA (RR 2.29; 95% CI 0.58-8.99) and those with other hemoglobinopathies (RR
      2.23; 95% CI 0.66-7.49) CONCLUSIONS: Osteomyelitis, pyomyositis and septic
      arthritis are common MSS infections in hospitalized pediatric and adolescent
      patients, while tuberculous arthritis is uncommon. The most common bacterial
      pathogen in these infections is S. aureus-even in patients with HbSS and other
      hemoglobinopathies. Gram-negative bacilli are important causes of MSS infections
      in hospitalized children with HbSS. HbSS may be an independent risk factor for
      osteomyelitis in these patients.

PMID- 14977283
TI  - Trends in the incidence, clinical presentation, and management of traumatic
      rupture of the corpus cavernosum.
AB  - BACKGROUND: Recent observations in our hospital of apparent increase in frequency
      prompted a revisit to the subject of fracture of penis. MATERIALS AND METHODS: In
      a retrospective review, patients' age, marital status, and causal activities;
      clinical presentations; methods of management; operative findings; and
      postoperative complications were analyzed for changing trends. Literature was
      also reviewed briefly. RESULTS: Nineteen episodes of penile fracture in 18
      patients exceed the previous incidence by more than 58%. Most were due to
      noncoital causes (73.7%); more unmarried people (31.6%) were affected. Most
      presented with the classic symptoms/signs, and tears were repaired by degloving
      through subcoronal incisions; one was treated conservatively. The higher
      morbidity observed was attributed to higher rates of hematoma and wound
      infections, probably enhanced by poor hemostasis and early persistent,
      postoperative erections. Painful erections, painful coitus, and deformities,
      however subsided within weeks, with no long-term ill effects. CONCLUSION: The
      incidence of penile fracture, postoperative hematoma, and infections has
      increased; about 32% of the patients were unmarried. The prominence of
      masturbation as a cause of penile fracture and increased ratio of noncoital to
      coital causes are highlighted. Degloving through subcoronal incisions remains an
      acceptable method of approach for repair in line with cultural practices in Saudi
      Arabia.

PMID- 14977284
TI  - Sonographic assessment of postvoid residual urine volumes in patients with benign
      prostatic hyperplasia.
AB  - OBJECTIVE: To derive a formula that defines the postvoid residual (PVR) urine
      volume more accurately in patients with prostatic gland enlargement. DESIGN:
      Prospective. SETTING: Department of Radiology, University of Ilorin Teaching
      Hospital, Ilorin. SUBJECT: Fifty-two consecutive patients with benign prostatic
      hyperplasia. The mean age was 64.98+/-9.57 years. METHOD: PVR urine was evaluated
      by ultrasonography. Each patient had two examinations, the first of which was
      with a full bladder and the second of which was immediately after voiding. Two
      orthogonal diameters were measured on each bladder section (longitudinal and
      transverse) in the supine position. Fifty-two paired sets of ultrasonic
      measurements were thus obtained. Catheterized postvoid urine residue was regarded
      as the gold standard. RESULTS: Using these measurements, an equation-
      [PVR(CUBIC)=374.057+(-196.94+V1)+(32.5539+V1(2))+(-1.1480+V1(3)) where V1=average
      of the length (L), width (T), and the anteroposterior distance on transverse
      section (Dt) of the postvoid urinary bladder]--more accurate than previously
      existing ones was obtained by cubic regression analysis. Mean ultrasound
      estimated volume was 220.51 ml as against 220.76 ml after catheterization. The
      mean difference was 0.25 ml (not significant, p<0.01) with 95% confidence
      interval of +/-10 ml. With this equation, the ultrasonographic residual urine
      volume showed a higher correlation coefficient with the catheterized volume at
      p<0.01 (Pearson r=0.982, r2=0.96) than previously defined formulas. The standard
      error of the mean was 5.11 ml (mean=220.5+/-190.4 ml). CONCLUSION: With the above
      equation, we consider conventional transabdominal ultrasonography a reliable
      method for assessing the residual urine volume in patients with benign prostatic
      hyperplasia. This equation, though complex when compared to some of the pre
      existing formulas, can be integrated into the memory of modern ultrasound
      machines for easy and faster computation.

PMID- 14977285
TI  - Secondary school athletes: a study of mouthguards.
AB  - The purpose of this study was to determine the extent of mouthguard awareness and
      use, as well as the amount and type of oro-facial trauma associated with and
      without mouthguard wear in adolescent Nigerian athletes. A 13-item self
      completion questionnaire was completed and returned by 1,127 secondary school
      athletes (completion rate of 93.9%) comprising 683 (60.6%) males and 444 (39.4%)
      females ranging in age from 12- to 19 years (mean age 15.18+/-2.97 SD). The
      athletes were randomly drawn from 23 secondary schools located in different parts
      of Ibadan city in Nigeria. Sixty-five-and-a-third percent of the athletes
      professed awareness of the need for mouthguards for sports, but only 19.6%
      claimed usage of the device. Thirty-four-and-a-half percent of the athletes
      reported having sustained one form of oro-facial injury or the other previously.
      The prevalence of oro-facial injuries was significantly lower while wearing a
      mouthguard (p<0.05), and most of the injuries occurred during contact sports. The
      study supports the need for the enforcement of mandatory mouthguard use in
      contact sports.

PMID- 14977286
TI  - John Henry Active Coping, education, and blood pressure among urban blacks.
AB  - The John Henryism hypothesis posits that individuals who actively cope with
      psychosocial stressors in the face of low socioeconomic resources are more likely
      to exhibit higher blood pressure levels than those with greater socioeconomic
      resources. It has been proposed that John Henryism may contribute to the
      disproportionately high rates of hypertension among blacks. Previous studies
      which support the John Henryism hypothesis have been conducted among blacks who
      reside in primarily southern rural settings. However, more recent studies
      conducted among urban blacks, have yielded contrasting results. This study
      examined the John Henryism hypothesis in a middle-aged urban sample of blacks in
      south Florida. The results of the study confirmed that there is indeed a
      relationship among John Henry Active Coping, years of education, and blood
      pressure among urban blacks in south Florida. Upon closer examination, higher
      John Henry Active Coping scores were associated with higher systolic and
      diastolic blood pressure among higher educated men, and John Henry Active Coping
      scores were associated with higher systolic and diastolic blood pressure among
      women with lower levels of education. The findings are discussed in terms of
      sociocultural factors that may influence the coping styles of black men and women
      in different communities and environments.

PMID- 14977287
TI  - Twenty-eight-year-old female with primary amenorrhea and chronic renal failure: a
      case of Frasier syndrome?
AB  - Frasier syndrome is a very rare developmental disorder of autosomal recessive
      inheritance. It is characterized by male hermaphroditism, primary amenorrhea,
      chronic renal failure (CRF), and a number of other abnormalities. A 28-year-old
      Nigerian female who was considered as a possible case of Frasier syndrome first
      presented to us in July 2002 with primary amenorrhea, congenital bilateral
      absence of middle toes, elevated blood pressure, and the uremic syndrome. The
      management of the case was mainly conservative, including blood pressure control
      with appropriate antihypertensives. The problems inherent in this index case are
      discussed while proffering appropriate management approach in a near-ideal
      situation, which unfortunately is nonexistent in our local environment. The
      presentation of this case is informed by the need to create awareness about this
      rare syndrome being a possible cause of CRF in some of our patients.

PMID- 14977288
TI  - Hepatitis C virus in sickle cell disease.

PMID- 14977289
TI  - Executive summary.

PMID- 14977290
TI  - Disparities and gaps in HIV research and care.

PMID- 14977291
TI  - HIV/AIDS prevention in Latino and African-American communities.

PMID- 14977292
TI  - Initiating antiretroviral therapy in asymptomatic HIV patients.

PMID- 14977293
TI  - Managing the metabolic and morphologic complications of HIV.

PMID- 14977294
TI  - The impact of substance abuse on the care of African Americans and Latinos with
      HIV/AIDS.

PMID- 14977295
TI  - HIV/HCV coinfection: management update.

PMID- 14977296
TI  - Improving adherence to HAART.

PMID- 14977297
TI  - Combating antiretroviral resistance.

PMID- 14977298
TI  - Herpesviral-bacterial coinfection in periapical pathosis.
AB  - Two members of the herpesvirus family, human cytomegalovirus (HCMV) and Epstein
      Barr virus (EBV), seem to be important putative pathogens of human periodontitis
      and symptomatic periapical lesions, causing pathosis either by inducing
      immunosuppression with a subsequent risk of aggressive bacterial infections or by
      infecting of periodontal cells directly. This study aimed to relate periapical
      occurrence of HCMV, EBV, and herpes simplex virus active infections to clinical
      characteristics of periapical lesions and periapical bacterial flora. Microbial
      samples were collected from 34 periapical lesions in conjunction with periapical
      surgery. Part of the periapical specimen was frozen for virologic examination,
      and another part was transferred to anaerobic transport medium for bacteriologic
      examination. RNA was isolated by means of a guanidinium isothiocyanate-acid
      phenol procedure, and cDNA was produced using herpesvirus-specific primers and
      reverse-transcription polymerase chain reaction amplification. Bacteriologic
      examination was performed according to established anaerobic culture methods. Of
      the 34 periapical lesions studied, 20 showed both HCMV and EBV, seven showed only
      HCMV, one showed only EBV, and six showed neither HCMV nor EBV. Herpes simplex
      virus was detected in two lesions. Higher occurrence of herpesvirus was detected
      in large versus small periapical lesions (p < 0.001) and in symptomatic versus
      asymptomatic periapical lesions (p < 0.001). A total of 18 microbial groups and
      an average of 2.1 to 3.0 bacterial groups were isolated from various categories
      of periapical lesions. The important finding of this study was that most teeth
      with necrotic pulp and periapical lesions harbored herpesviruses in periapical
      granulomatous tissue. Herpesvirus species in cooperation with endodontopathic
      bacteria may play major roles in the etiopathogenesis of aggressive types of
      periapical pathosis in humans.

PMID- 14977299
TI  - Radiographic evaluation of root canal multiplicity in mandibular first premolars.
AB  - The purpose of this study was to examine the accuracy of radiographic evaluation
      of root canal multiplicity in mandibular first premolars in vitro. One hundred
      thirty-nine extracted human mandibular premolars were used. Buccolingual
      radiographs were taken, and the number of canals in each tooth was determined on
      radiographs by four dentists using a view box. A sudden narrowing of the main
      canal was interpreted as a sign of multiple canals. After the radiographic
      evaluation, the tooth crown was removed. India ink was injected into the root
      canal system, and the root was cleared to observe the canal morphology. There was
      no statistically significant difference among the four dentists with respect to
      the coincidence rate (93%-96%) of the canal number evaluated on radiographs with
      that identified by cleared teeth observation (p > 0.05, one-way analysis of
      variance). A sudden narrowing of the main canal on the radiograph was a good
      criterion to judge root canal multiplicity.

PMID- 14977300
TI  - Relationship of radiologic and histologic signs of inflammation in human root
      filled teeth.
AB  - The aim of this study was to determine the relationship between histologic and
      radiologic signs of inflammation in human root-filled teeth. In addition, other
      factors with possible importance for apical inflammation were assessed. Fifty
      three block sections of root-filled teeth were gathered from human cadavers. The
      blocks were radiographically exposed, sectioned, and stained with hematoxylin and
      eosin. Histologic sections were categorized as inflamed or uninflamed.
      Radiographically, the roots were assigned as apical lucency, widened periodontal
      ligament (PDL), or no lucency. Presence and contents of accessory canals were
      recorded (empty, tissue, or filling material). Statistical analysis was performed
      with the Chi-square test. All roots had accessory canals; 12 showed tissue
      remnants, and the others were empty. Of the cases, 49% were histologically
      uninflamed at the apex, and 52% appeared radiographically intact. The odds ratio
      of finding a histologically inflamed apex with radiologic lucency versus a
      radiographically intact apex was 9.2 (p = 0.002). The odds ratio of finding a
      histologically uninflamed apex with a radiologically tight coronal seal versus an
      unacceptable seal was 3.7 (p = 0.053). It may be concluded that there are
      relationships between radiologic and histologic signs of inflammation in human
      root canal-treated teeth. There appears to be a tendency that the radiologically
      determined quality of the coronal seal has an impact on the histologic state of
      the root-filled tooth. No relationship was detected between unfilled lateral or
      accessory canals and the status of inflammation at the periapex (51% inflamed,
      49% uninflamed).

PMID- 14977301
TI  - Repair of root perforations using mineral trioxide aggregate: a long-term study.
AB  - Root perforations adversely affect the prognosis of teeth. Inadequacy of the
      repair materials has been a contributing factor to the poor outcome of repair
      procedures. Mineral trioxide aggregate (MTA) is a relatively new material that is
      being successfully used to repair perforations. The purpose of this study was to
      evaluate the success rate of root perforation repairs using MTA. A list of all of
      the perforation repairs completed with MTA at an endodontic residency program was
      obtained. Sixteen cases were included that met the criteria for this study.
      Pretreatment, immediate posttreatment, and at least 1 year follow-up radiographs
      were evaluated in a double-blind manner to determine the presence or absence of
      any pathologic changes adjacent to the perforation site. The results showed that
      all 16 cases demonstrated normal tissue architecture adjacent to the repair site
      at the recall visit. Teeth with existing lesions showed resolution of the lesion,
      and teeth without preoperative lesions continued to demonstrate absence of lesion
      formation at the follow-up visit. Based on the results of this study, MTA
      provides an effective seal of root perforations and shows promise in improving
      the prognosis of perforated teeth that would otherwise be compromised.

PMID- 14977302
TI  - Antibacterial activity of 2% chlorhexidine gluconate and 5.25% sodium
      hypochlorite in infected root canal: in vivo study.
AB  - In this study, the antibacterial activity of the different antibacterial
      solutions using as root canal irrigant was compared in the teeth with pulpal
      necrosis and with periapical pathosis. Thirty root canals of incisors and
      premolars of 20 patients were used. Before and after the root canal preparation,
      two canal samples were obtained by a harvesting method using a sterile paper
      point in the first appointment. During the biomechanical preparation, both
      irrigant solutions were used for each tooth which were randomly divided into two
      groups. Last samples were also obtained before the root filling procedure.
      Samples obtained from the root canals were subjected to microbiologic processing,
      including anaerobic incubation on trypticase soy agar for 5 to 7 days. After
      counting of CFU on the plates, we concluded that both chlorhexidine gluconate and
      sodium hypochlorite were significantly effective to reduce the microorganisms in
      the teeth with necrotic pulp, periapical pathologies, or both, and could be used
      successfully as an irrigant solution.

PMID- 14977303
TI  - Proinflammatory cytokine profiles in pulp fibroblasts stimulated with
      lipopolysaccharide and methyl mercaptan.
AB  - Pulpal disease is intimately associated with the immune system's response to
      bacteria products. Clinical pathology is mediated in part by the production of
      pyrogenic cytokines, especially interleukin (IL)-1, tumor necrosis factor (TNF)
      alpha, and IL-6. Methyl mercaptan (CH3SH), a volatile sulfur compound produced by
      anaerobic Gram-negative bacteria, has been shown to contribute to the production
      of IL-1 by human mononuclear cells. In this report, we investigated the
      production of IL-1, TNF-alpha, and IL-6 by human pulp fibroblasts when stimulated
      for various periods of time with lipopolysaccharide (LPS) with or without the
      presence of CH3SH. We found that LPS and CH3SH had no effect on the production of
      IL-1 or TNF-alpha. However, LPS stimulated IL-6 production, and this production
      was augmented when CH3SH was present. We conclude that the volatile sulfur
      compound CH3SH plays a role in activation and modulation of the immune response
      through its role in production of IL-6.

PMID- 14977304
TI  - Effectiveness of sodium hypochlorite in preventing inoculation of periapical
      tissues with contaminated patency files.
AB  - The aim of this study was to analyze the effectiveness of 5.25% sodium
      hypochlorite (NaOCI) in preventing inoculation of periapical tissues with
      contaminated patency files. Twenty-eight extracted human permanent teeth with
      single canals were used in the study. Group I teeth were filled with NaOCl, and
      #15 stainless steel files contaminated with Streptococcus sanguis (ATCC #10556)
      were allowed to pass through the NaOCI into the culture medium. The teeth in
      group II were also filled with NaOCl, but the contaminated files used in group II
      canals were immersed in NaOCl for 10 s prior to being placed into the canals and
      cultured. The negative control group used sterile files (0% growth), the first
      positive control group used contaminated patency files in teeth with empty canals
      (100% growth), and the second positive control group placed contaminated files
      into broth next to teeth filled with NaOCl (to evaluate potential chlorine
      leakage; 100% growth). The experimental results showed no positive growth of S.
      sanguis for groups I and II, indicating that the NaOCl present in the canal after
      irrigation was sufficient to kill the test organism.

PMID- 14977305
TI  - Reactions of connective tissue to mineral trioxide aggregate and amalgam.
AB  - The purpose of this study was to evaluate the subcutaneous connective tissue
      reactions to ProRoot, mineral trioxide aggregate (MTA; Dentsply), and Oralloy,
      high-copper amalgam (Coltene). These materials were placed in polyethylene tubes
      and implanted into dorsal connective tissue of Wistar albino rats, and tissue
      biopsies were collected and histologically examined 7, 15, 30, 60, and 90 days
      after the implantation procedure. The presence of inflammation, predominant cell
      type, calcification, and thickness of fibrous connective tissue were recorded.
      Scores were defined as follows: 0, none or few inflammatory cells, no reaction;
      1, < 25 cells, mild reaction; 2, 25 to 125 cells, moderate reaction; 3, > or =
      125 cells, severe reaction. Fibrous capsule was categorized as "thin" when
      thickness was < 150 microm and "thick" at > 150 microm. Necrosis and formation of
      calcification were recorded. Both materials were well tolerated by the tissues in
      a 90-day evaluation period. One notable finding is the presence of dystrophic
      calcification in connective tissue adjacent to MTA; this finding is consistent
      with the hypothesis of hard tissue induction by this material.

PMID- 14977306
TI  - The influence of the smear layer on dentinal tubule penetration depth by three
      different root canal sealers: an in vitro study.
AB  - The effect of the smear layer on the penetration depth of three different root
      canal sealers into the dentinal tubules was examined in 64 recently extracted
      single-rooted teeth. After chemomechanical preparation, the samples were randomly
      divided in two equal groups. The smear layer remained intact in group A, whereas
      complete removal of the smear layer was performed in group B. Two roots from each
      group were used as controls. Ten roots from each group were obturated with
      laterally condensed gutta-percha points and sealers AH Plus, Apexit, and Roth
      811, respectively. Examination in scanning electron microscope revealed that the
      smear layer obstructed all the sealers from penetrating dentinal tubules. In
      contrast, smear layer removal allowed the penetration of all sealers to occur to
      a varying depth. These findings suggest that smear layer plays an important role
      in sealer penetration into the dentinal tubules, as well as in the potential
      clinical implications.

PMID- 14977307
TI  - A comparison of laterally condensed gutta-percha, thermoplasticized gutta-percha,
      and mineral trioxide aggregate as root canal filling materials.
AB  - The purpose of this study was to evaluate the potential of using mineral trioxide
      aggregate as a root canal filling material by comparing its apical sealing
      ability with that of laterally condensed gutta-percha with sealer and high
      temperature thermoplasticized gutta-percha with sealer in extracted bovine teeth.
      Sixty bovine incisors with single canals were prepared in a standard manner using
      LightSpeed instruments, randomly divided into three groups of 20 teeth, and
      obturated. The sealing ability of each technique was assessed by immersion in 1%
      methylene blue dye for 3 days. The teeth were cleared, and the linear extent of
      dye penetration was measured with a stereomicroscope. Data were analyzed by the
      Kruskal-Wallis one-way ANOVA followed by Dunn's test. Canals filled with
      laterally condensed gutta-percha or thermoplasticized gutta-percha showed
      significantly less apical dye penetration than canals obturated with mineral
      trioxide aggregate (p < 0.001). There was no significant difference in leakage
      between the laterally condensed group and the thermoplasticized group. The
      results suggest that gutta-percha obturation may provide an apical seal that is
      superior to MTA.

PMID- 14977308
TI  - Comparison instrumentation reamers and files versus a flat-sided design of
      conventional noninterrupted, flat-sided design.
AB  - The in vitro study measured the time required to instrument and shape canals by
      conventional reamers and files compared with a newly introduced reamer and file
      system. This experiment was divided into four groups with 10 block samples for
      each group. The results of instrumentation time demonstrate that the
      noninterrupted flat-sided design (EZ-Fill SafeSider reamers) produced the fastest
      times for comparably shaped canals because of reduced engagement of the
      instrument with the walls of the canal compared with conventional instruments.
      The conventional designs for both reamers and files result in increased
      instrumentation time compared with their EZ-Fill SafeSider counterparts.

PMID- 14977309
TI  - Influence of instrument size on root canal debridement.
AB  - Files of Greater Taper (GT) are rotary nickel-titanium files of three tapers
      (0.06, 0.08, 0.10) with file tips of sizes 20, 30, and 40. The purpose of this
      study was to compare in an in situ model the efficacy of root canal debridement
      in the apical 3 mm when instrumenting to a GT size 20 or a GT size 40 at working
      length. Twenty matched human cadaver teeth with 32 canals were decoronated at the
      cementoenamel junction and instrumented with rotary Files of GT to either GT size
      20 or GT size 40. Sodium hypochlorite, EDTA, and RC Prep were chemical aids for
      debridement. The teeth were extracted; decalcified; sectioned at 0.5 mm, 1.5 mm,
      and 2.5 mm from the apex; and prepared for histologic examination and
      quantification of remaining debris. No differences were found between each level
      within each apex size group; however, the GT size 20 group left significantly
      more debris in the apical third compared with the GT size 40 group. A regression
      analysis showed that the apical third cleanliness could be predicted mainly by
      instrument size and to a lesser extent by the canal length. Irrigant volume,
      number of instrument changes, and depth of penetration of irrigation needle were
      not likely to explain differences in debridement.

PMID- 14977310
TI  - Effect of medications for root canal treatment on bonding to root canal dentin.
AB  - Use of resin-based restorative materials recently has become widely accepted for
      treatment of endodontically treated teeth. However, some solutions routinely used
      during endodontic treatment procedures may have an effect on bond strengths of
      adhesive materials to root canal dentin. The purpose of this in vitro study was
      to evaluate the effect of various medications on microtensile bond strength to
      root canal dentin. Fourteen extracted human single-rooted teeth were used. The
      crowns and the pulp tissues were removed. The root canals were then instrumented
      and widened to the same size. The teeth were randomly divided into seven groups
      of two teeth each. The root canal dentin walls of the roots were treated with 5%
      sodium hypochloride (NaOCI), 3% hydrogen peroxide (H2O2), the combination of H2O2
      and NaOCl, or 0.2% chlorhexidine gluconate for 60 s; or calcium hydroxide or
      formocresol for 24 h. The teeth in control group were irrigated with water. The
      root canals were obturated using C&B Metabond. After 24 h of storage in distilled
      water, serial 1-mm-thick cross-sections were cut, and approximately 12 samples
      were obtained from each group. Microtensile bond strengths to root canal dentin
      were then measured by using an Instron machine. The data were recorded and
      expressed as MPa. The results indicated that NaOCI, H2O2, or a combination of
      NaOCl and H2O2 treatment decreased bond strength to root canal dentin
      significantly (p < 0.05). The teeth treated with chlorhexidine solution showed
      the highest bond strength values (p < 0.05). In conclusion, chlorhexidine is an
      appropriate irrigant solution for root canal treatment before adhesive post core
      applications.

PMID- 14977311
TI  - Mental nerve paresthesia associated with an adhesive resin restoration: a case
      report.
AB  - A case is reported in which mental nerve paresthesia was associated with an
      adhesive resin restoration placed in direct contact with the pulp of a mandibular
      molar. The restoration was removed, and the paresthesia had completely resolved
      after nonsurgical endodontic therapy. Epicutaneous patch testing response
      indicated a possible causal relationship between the filling material and
      paresthesia.

PMID- 14977312
TI  - MTA for obturation of mandibular central incisors with open apices: case report.
AB  - The case reported demonstrates dramatic healing of the periapical region of
      retreated root canals with open apices by the successful use of mineral trioxide
      aggregate (MTA). Unsuccessful conventional root canal therapy for the mandibular
      central incisors had been followed by surgical treatment. The severely damaged
      root canals were obturated using MTA in anticipation of the formation of
      artificial apical plugs. The treated teeth were asymptomatic, and radiographic
      examination demonstrated apparent regeneration of periradicular tissue 2 years
      after the obturation. MTA can be considered a very effective material to promote
      regeneration of apical tissue, even in teeth with large open apices.

PMID- 14977313
TI  - Poised for public awareness.

PMID- 14977314
TI  - Quantification of highway vehicle emissions hot spots based upon on-board
      measurements.
AB  - The purpose of this study is to demonstrate a methodology for quantification of
      high emissions hot spots along roadways based upon real-world, on-road vehicle
      emissions measurements. An emissions hot spot is defined as a fixed location
      along a corridor in which the peak emissions are statistically significantly
      greater by more than a factor of 2 than the average emissions for free-flow or
      near free-flow conditions on the corridor. A portable instrument was used to
      measure on-road tailpipe emissions of carbon monoxide, nitric oxide,
      hydrocarbons, and carbon dioxide on a second-by-second basis during actual
      driving. Measurements were made for seven vehicles deployed on two primary
      arterial corridors. The ratio of average emissions at hot spots to the average
      emissions observed during a trip was as high as 25 for carbon monoxide, 5 for
      nitric oxide, and 3 for hydrocarbons. The relationships between hot spots and
      explanatory variables were investigated using graphical and statistical methods.
      Average speed, average acceleration, standard deviation of speed, percent of time
      spent in cruise mode, minimum speed, maximum acceleration, and maximum power have
      statistically significant associations with vehicle emissions and influence
      emissions hot spots. For example, stop-and-go traffic conditions that result in
      sudden changes in speed, and traffic patterns with high accelerations, are shown
      to generate hot spots. The implications of this work for future model development
      and applications to environmental management are discussed.

PMID- 14977315
TI  - Assessment of influential range and characteristics of fugitive dust in limestone
      extraction processes.
AB  - Fugitive dust emission from limestone extraction areas is a significant pollution
      source. The cracking operation in limestone extraction areas easily causes high
      total suspended particulate (TSP) concentrations in the atmosphere, occasionally
      exceeding the 1-hr national emission standard of Taiwan (500 microg/m3). The
      concentration and size distribution were measured at different distances (0.05-15
      km) in the extraction areas. The highest hourly concentrations of TSP, PM10
      (suspended particulate matter [PM] smaller than 10 microm), and PM2.5 (suspended
      PM smaller than 2.5 microm) are 1111, 825, and 236 microg/m3, respectively,
      during the cracking process. Measurement results obtained from the Micro-Orifice
      Uniform Deposit Impactor indicated that the mass median aerodynamic diameter is
      approximately 0.7 microm, with the geometric standard deviation exceeding 7. In
      addition, the emission factors are 0.143 and 0.211 kg/t for both vertical well
      and stair extraction operations, respectively. Experimental results demonstrate
      that the corresponding TSP control efficiencies for spraying water, planting
      grass, setting short walls, paving gravel roads, and establishing vertical well
      transportation are approximately 55, 50, 44, 22, and 30%, respectively.
      Furthermore, the PM10 control efficiencies are approximately 45, 41, 54, 35, and
      30%, respectively, whereas the PM2.5 control efficiencies are roughly 23, 31, 15,
      11, and 10%, individually.

PMID- 14977316
TI  - A mechanistic model for mercury capture with in situ-generated titania particles:
      role of water vapor.
AB  - A mechanistic model to predict the capture of gas-phase mercury (Hg) species
      using in situ-generated titania nanosize particles activated by UV irradiation is
      developed. The model is an extension of a recently reported model for
      photochemical reactions by Almquist and Biswas that accounts for the rates of
      electron-hole pair generation, the adsorption of the compound to be oxidized, and
      the adsorption of water vapor. The role of water vapor in the removal efficiency
      of Hg was investigated to evaluate the rates of Hg oxidation at different water
      vapor concentrations. As the water vapor concentration is increased, more hydroxy
      radical species are generated on the surface of the titania particle, increasing
      the number of active sites for the photooxidation and capture of Hg. At very high
      water vapor concentrations, competitive adsorption is expected to be important
      and reduce the number of sites available for photooxidation of Hg. The
      predictions of the developed phenomenological model agreed well with the measured
      Hg oxidation rates in this study and with the data on oxidation of organic
      compounds reported in the literature.

PMID- 14977317
TI  - An analysis of candidates for addition to the Clean Air Act list of hazardous air
      pollutants.
AB  - There are 188 air toxics listed as hazardous air pollutants (HAPs) in the Clean
      Air Act (CAA), based on their potential to adversely impact public health. This
      paper presents several analyses performed to screen potential candidates for
      addition to the HAPs list. We analyzed 1086 HAPs and potential HAPs, including
      chemicals regulated by the state of California or with emissions reported to the
      Toxics Release Inventory (TRI). HAPs and potential HAPs were ranked by their
      emissions to air, and by toxicity-weighted (tox-wtd) emissions for cancer and
      noncancer, using emissions information from the TRI and toxicity information from
      state and federal agencies. Separate consideration was given for persistent,
      bioaccumulative toxins (PBTs), reproductive or developmental toxins, and
      chemicals under evaluation for regulation as toxic air contaminants in
      California. Forty-four pollutants were identified as candidate HAPs based on
      three ranking analyses and whether they were a PBT or a reproductive or
      developmental toxin. Of these, nine qualified in two or three different rankings
      (ammonia [NH3], copper [Cu], Cu compounds, nitric acid [HNO3], N-methyl-2
      pyrrolidone, sulfuric acid [H2SO4], vanadium [V] compounds, zinc [Zn], and Zn
      compounds). This analysis suggests further evaluation of several pollutants for
      possible addition to the CAA list of HAPs.

PMID- 14977318
TI  - Estimation of vinyl chloride emissions from gasholders and validation of in situ
      emission reduction methods.
AB  - Gasholders consist of a floating bell in a tank filled with water. Water provides
      a seal between the enclosed gas and ambient air. Gasholder emissions come from
      the contaminated water seal exposed to ambient air and the wet bell wall. The
      study objectives were to define parameters influencing gasholder emissions,
      determine the quantities of vinyl chloride (VC) emitted, generate a correlation
      equation between parameters of influence and mass emissions, and evaluate the
      efficiency of emission reduction methods. The research project was carried out on
      a laboratory-scale representation of a gasholder. The classic two-phase
      resistance model was used successfully to generate a correlation equation, which
      can be used to calculate the gasholder water seal emissions. A strictly empirical
      model was generated to estimate the wet wall emissions. Two in situ reduction
      methods were evaluated with the laboratory installations: floating objects and an
      oil layer. Both methods showed significant emission reductions, but the oil layer
      was the most effective. To reduce emissions even further, it is recommended that
      the water level of the gasholder be set to the lowest achievable level, that a
      windshield be placed around the water seal perimeter, and that hydrophobic paint
      be used on the bell wall.

PMID- 14977319
TI  - Manganese content of Tradescancia species exposed to automotive combustion of
      methylcyclopentadienyl manganese tricarbonyl in urban and rural landscapes.
AB  - The purpose of this study is to assess the effect of manganese (Mn) from
      methylcyclopentadienyl manganese tricarbonyl (MMT) on grass (Tradescancia)
      species beside the major urban and rural highways in the greater Toronto area.
      Grass clippings were collected at distances up to 40 m from the roadside of a
      wooded, weakly exposed site (E+) and two unwooded, highly exposed sites (E++ and
      E+++) to Mn contamination. Statistical tests, including analysis of variance and
      correlation coefficients, were used to compare the Mn deposition on grass species
      with respect to distance and traffic density. A higher deposition of Mn was
      expected at the highly exposed sites when compared with the weakly exposed site,
      but a significantly higher concentration of Mn was observed at weakly exposed
      rural E+ site (Mn = 54.07 microg/g; dry wt) than the highly exposed urban E++ (Mn
      = 38.17 microg/g; dry wt) and E+++ (Mn = 35.63 microg/g; dry wt) sites. A
      significant correlation coefficient was found for Mn and traffic density (r2 =
      0.311, p = 0.0074) at the weakly exposed site than at the highly exposed (r2 =
      0.1589, p = 0.1052) urban sites. These data demonstrate that despite the
      continuous use of MMT in Canadian gasoline, the levels do not appear to exceed
      the worldwide tolerable levels (17-334 g/g; dry wt) in grass species inhabiting
      ecosystems next to major highways in urban regions.

PMID- 14977320
TI  - An optimal model and its application for the management of municipal solid waste
      from regional small cities in China.
AB  - Based on the basic characteristics of municipal solid waste (MSW) from regional
      small cities in China, some optimal management principles have been put forward:
      regional optimization, long-term optimization, and integrated treatment/disposal
      optimization. According to these principles, an optimal MSW management model for
      regional small cities is developed and provides a useful method to manage MSW
      from regional small cities. A case study application of the optimal model is
      described and shows that the optimal management scenarios in the controlling
      region can be gained, adequately validating and accounting for the advantages of
      the optimal model.

PMID- 14977321
TI  - Emissions and demonstration of an emission control technology for small two
      stroke utility engines.
AB  - Small utility engines represent an important contribution to the emissions
      inventory and have been subjected to increasingly stringent regulations in recent
      years. For this project, a Tanaka two-stroke engine was tested in its original
      condition and with a modified fuel/oil injection system. The modified fuel/oil
      injection system applied to the Tanaka two-stroke engine resulted in significant
      emissions reductions of approximately 52% for carbon monoxide (CO), 70% for total
      hydrocarbons (THC), 70% for particulate matter (PM), and 67% for the regulated
      THC + nitrogen oxides metric. This technology met the California Air Resources
      Board's 2000 model-year regulations for all pollutants, with the exception of
      slightly higher PM emissions. Two additional two-stroke engines were tested under
      a new condition and after at least 100 hr of use to examine the effects of
      deterioration on in-use, two-stroke engines. For one engine, CO and PM emissions
      more than tripled after 162 hr of operation in the field, with smaller increases
      also observed for THC (20%). For the second engine, significant repairs were
      required throughout the 100 operating hours, which counteracted the effects of
      the emissions deterioration and resulted in lower CO and THC emissions.

PMID- 14977322
TI  - Personal exposures to particles and their relationships with personal activities
      for chronic obstructive pulmonary disease patients living in Boston.
AB  - An exposure study of 18 subjects with chronic obstructive pulmonary disease
      (COPD) living in the Boston, MA, area was conducted. The objective was to examine
      determinants of personal exposures to particulate matter (PM) with aerodynamic
      diameters of less than 2.5 microm (PM2.5), less than 10 microm (PM10), and
      between 2.5 and 10 microm (PM2.5-10). In a previous publication, the analyses of
      the longitudinal individual-specific relationships among indoor, outdoor, and
      personal levels showed that the relationships varied by subject and by particle
      size fraction. In the present paper, statistical and physical models were used to
      examine personal PM2.5, PM10, and PM2.5-10 exposure covariates. Results indicated
      that time-weighted indoor concentrations were significant predictors of personal
      PM2.5, PM10, and PM2.5-10 exposures. Also, time-weighted outdoor concentrations,
      time spent near smokers, and time spent during transportation were important
      predictors for PM2.5 but not for personal PM2.5-10 exposures. In turn, time spent
      cleaning contributed to all size-fraction personal exposures, whereas cooking
      affected only personal PM2.5-10 exposures. The findings showed that the
      relationship between personal PM2.5 exposures and the corresponding ambient
      concentrations was influenced by home air exchange rates (or by ventilation
      status). Because the particle properties or components causing the health effects
      are unknown, it is not certain to what extent the risk posed by ambient particles
      can be reduced by controlling any one of these factors.

PMID- 14977323
TI  - Inorganic acid emission factors of semiconductor manufacturing processes.
AB  - A huge amount of inorganic acids can be produced and emitted with waste gases
      from integrated circuit manufacturing processes such as cleaning and etching.
      Emission of inorganic acids from selected semiconductor factories was measured in
      this study. The sampling of the inorganic acids was based on the porous metal
      denuders, and samples were then analyzed by ion chromatography. The amount of
      chemical usage was adopted from the data that were reported to the Environmental
      Protection Bureau in Hsin-chu County according to the Taiwan Environmental
      Protection Agency regulation. The emission factor is defined as the emission rate
      (kg/month) divided by the amount of chemical usage (L/month). Emission factors of
      three inorganic acids (i.e., hydrofluoric acid [HF], hydrochloric acid [HCl], and
      sulfuric acid [H2SO4]) were estimated by the same method. The emission factors of
      HF and HCl were determined to be 0.0075 kg/L (coefficient of variation [CV] =
      60.7%, n = 80) and 0.0096 kg/L (CV = 68.2%, n = 91), respectively. Linear
      regression equations are proposed to fit the data with correlation coefficient
      square (R2) = 0.82 and 0.9, respectively. The emission factor of H2SO4, which is
      in the droplet form, was determined to be 0.0016 kg/L (CV = 99.2%, n = 107), and
      its R2 was 0.84. The emission profiles of gaseous inorganic acids show that HF is
      the dominant chemical in most of the fabricators.

PMID- 14977324
TI  - Development and application of protocols for the determination of response of
      real-time particle monitors to common indoor aerosols.
AB  - Protocols have been developed and applied for the generation of aerosols that are
      likely to be comparable to those encountered in field settings for the
      calibration of easily transportable/portable real-time particle monitors.
      Aerosols generated were simulated environmental tobacco smoke, cedar wood smoke,
      cooking oil fumes, and propane stove particles. The time-integrated responses of
      three nephelometers and a monitor for particle-bound polynuclear aromatic
      hydrocarbons (PAH) were compared with gravimetric respirable suspended
      particulate matter (RSP) in a controlled-atmosphere chamber. In general, the
      monitor responses increased linearly with increasing mass concentration. However,
      the two monitors that reported mass per volume concentrations tended to
      overreport the actual RSP concentrations by factors up to 4.4. The real-time PAH
      monitor did not respond to cooking oil fumes, indicative of little PAH being
      present in the aerosol. One of the monitors that has been used in a variety of
      studies reported in the literature (DustTrak) was collocated with gravimetric RSP
      samplers in several hospitality venues in the Louisville, KY, area. Field studies
      indicated that the units overreported actual RSP concentrations by factors of 2.6
      3.1, depending on whether the sampling was conducted in the nonsmoking or smoking
      sections of the facilities.

PMID- 14977325
TI  - Performance of an innovative two-stage process converting food waste to hydrogen
      and methane.
AB  - This study was conducted to evaluate the performance of an innovative two-stage
      process, BIOCELL, that was developed to produce hydrogen (H2) and methane (CH4)
      from food waste on the basis of phase separation, reactor rotation mode, and
      sequential batch technique. The BIOCELL process consisted of four leaching-bed
      reactors for H2 recovery and post-treatment and a UASB reactor for CH4 recovery.
      The leaching-bed reactors were operated in a rotation mode with a 2-day interval
      between degradation stages. The sequential batch technique was useful to optimize
      environmental conditions during H2 fermentation. The BIOCELL process demonstrated
      that, at the high volatile solids (VS) loading rate of 11.9 kg/m3 x day, it could
      remove 72.5% of VS and convert VS(removed) to H2 (28.2%) and CH4 (69.9%) on a
      chemical oxygen demand (COD) basis in 8 days. H2 gas production rate was 3.63
      m3/m3 x day, while CH4 gas production rate was 1.75 m3/m3 x day. The yield values
      of H2 and CH4 were 0.31 and 0.21 m3/kg VS(added), respectively. Moreover, the
      output from the post-treatment could be used as a soil amendment. The BIOCELL
      process proved to be stable, reliable, and effective in resource recovery as well
      as waste stabilization.

PMID- 14977327
TI  - Retinal projections in the cat: a cholera toxin B subunit study.
AB  - The B fragment of cholera toxin (CTb) is a highly sensitive anterograde tracer
      for the labelling of retinal axons. It can reveal dense retinofugal projections
      to well-known retinorecipient nuclei along with sparse but distinct input to
      target areas that are not commonly recognized. Following a unilateral injection
      of CTb into the vitreous chamber of seven adult cats, we localized the toxin
      immunohistochemically in order to identify direct retinal projections in these
      animals. Consistent with previous findings, the strongest projections were
      observed in the superficial layers of the superior colliculus, the dorsal and
      ventral lateral geniculate nuclei, the pretectal nuclei, the accessory optic
      nuclei, and the suprachiasmatic nucleus of the hypothalamus. However, we also
      found labelled terminals in several other brain areas, including the zona
      incerta, the medial geniculate nucleus, the lateral posterior-pulvinar complex,
      the lateral habenular nucleus, and the anterior and lateral hypothalamic regions.
      The morphological characteristics of the retinal axon terminals in most of the
      identified novel target sites are described.

PMID- 14977326
TI  - A model of high-frequency oscillatory potentials in retinal ganglion cells.
AB  - High-frequency oscillatory potentials (HFOPs) have been recorded from ganglion
      cells in cat, rabbit, frog, and mudpuppy retina and in electroretinograms (ERGs)
      from humans and other primates. However, the origin of HFOPs is unknown. Based on
      patterns of tracer coupling, we hypothesized that HFOPs could be generated, in
      part, by negative feedback from axon-bearing amacrine cells excited via
      electrical synapses with neighboring ganglion cells. Computer simulations were
      used to determine whether such axon-mediated feedback was consistent with the
      experimentally observed properties of HFOPs. (1) Periodic signals are typically
      absent from ganglion cell PSTHs, in part because the phases of retinal HFOPs vary
      randomly over time and are only weakly stimulus locked. In the retinal model,
      this phase variability resulted from the nonlinear properties of axon-mediated
      feedback in combination with synaptic noise. (2) HFOPs increase as a function of
      stimulus size up to several times the receptive-field center diameter. In the
      model, axon-mediated feedback pooled signals over a large retinal area, producing
      HFOPs that were similarly size dependent. (3) HFOPs are stimulus specific. In the
      model, gap junctions between neighboring neurons caused contiguous regions to
      become phase locked, but did not synchronize separate regions. Model-generated
      HFOPs were consistent with the receptive-field center dynamics and spatial
      organization of cat alpha cells. HFOPs did not depend qualitatively on the exact
      value of any model parameter or on the numerical precision of the integration
      method. We conclude that HFOPs could be mediated, in part, by circuitry
      consistent with known retinal anatomy.

PMID- 14977328
TI  - Video-rate and continuous visual stimuli do not produce equivalent response
      timings in visual cortical neurons.
AB  - Video cathode ray tube (CRT) technology has proven to be extremely valuable for
      performing research in the visual system. However, the image on a CRT monitor is
      not constant, but consists of a series of brief pulses. This has implications for
      any study that explores the responses of neurons in the visual system on short
      time scales. In particular, there is no unambiguous time point at which a visual
      stimulus presented via CRT may be said to have ended. Recordings from single
      units in visual cortical area V1 of an awake primate demonstrate that, when
      studying changes in response timing on the order of 10 ms or less, stimuli
      delivered at video frame rates do not duplicate the effects seen with stimuli
      that have continuous functions of luminance versus time. Additionally, there does
      not seem to be any clear method of comparing the results obtained with video-rate
      stimuli with results obtained with continuous-time stimuli that holds for all
      conditions. These effects are especially critical when exploring the time course
      of the neuronal responses to the ending of a visual stimulus (off-response). Our
      findings cast doubt upon the recently reported result that off-responses have
      consistently shorter latencies than on-responses.

PMID- 14977329
TI  - Hyper-vision in a patient with central and paracentral vision loss reflects
      cortical reorganization.
AB  - SM, a 21-year-old female, presents an extensive central scotoma (30 deg) with
      dense absolute scotoma (visual acuity = 10/100) in the macular area (10 deg) due
      to Stargardt's disease. We provide behavioral evidence of cortical plastic
      reorganization since the patient could perform several visual tasks with her poor
      vision eyes better than controls, although high spatial frequency sensitivity and
      visual acuity are severely impaired. Between 2.5-deg and 12-deg eccentricities,
      SM presented (1) normal acuity for crowded letters, provided stimulus size is
      above acuity thresholds for single letters; (2) a two-fold sensitivity increase
      (d-prime) with respect to controls in a simple search task; and (3) largely above
      threshold performance in a lexical decision task carried out randomly by
      controls. SM's hyper-vision may reflect a long-term sensory gain specific for
      unimpaired low spatial-frequency mechanisms, which may result from modifications
      in response properties due to practice-dependent changes in excitatory/inhibitory
      intracortical connections.

PMID- 14977330
TI  - Chromatic detection and discrimination in the periphery: a postreceptoral loss of
      color sensitivity.
AB  - The peripheral visual field is marked by a deterioration in color sensitivity,
      sometimes attributed to the random wiring of midget bipolar cells to cone
      photoreceptors in the peripheral retina (Mullen, 1991; Mullen & Kingdom, 1996).
      Using psychophysical methods, we explored differences in the sensitivity of
      peripheral color mechanisms with detection and discrimination of 2-deg spots at
      18-deg eccentricity, and find evidence for a postreceptoral locus for the
      observed loss in sensitivity. As shown before, observers' sensitivity to green
      was lower than to red in the periphery, although the magnitude of this effect
      differed across observers. These results suggest that the asymmetry in peripheral
      sensitivity occurs at a postreceptoral site, possibly a cortical one. In
      addition, noise masking was used to determine the cone inputs to the peripheral
      color mechanisms. The masked detection contours indicate that the red and green
      mechanisms in the periphery respond to the linear difference of approximately
      equally weighted L- and M-cone contrasts, just as they do in the fovea. Thus, if
      the midget retinal ganglion system is responsible for red/green color perception
      in the fovea, it is likely to be responsible at 18-deg eccentricity as well.

PMID- 14977331
TI  - Limulus opsins: diurnal regulation of expression.
AB  - Much has been learned from studies of Limulus photoreceptors about the role of
      the circadian clock and light in the removal of photosensitive membrane. However,
      little is known in this animal about mechanisms regulating photosensitive
      membrane renewal, including the synthesis of proteins in, and associated with,
      the photosensitive membrane. To begin to understand renewal, this study examines
      diurnal changes in the levels of mRNAs encoding opsin, the integral membrane
      protein component of visual pigment, and the relative roles of light and the
      circadian clock in producing these changes. We show that at least two distinct
      opsin genes encoding very similar proteins are expressed in both the lateral and
      ventral eyes, and that during the day and night in the lateral eye, the average
      level of mRNA encoding opsinl is consistently higher than that encoding opsin2.
      Northern blot assays showed further that total opsin mRNA in the lateral eyes of
      animals maintained under natural illumination increases during the afternoon (9 &
      12 h after sunrise) in the light and falls at night in the dark. This diurnal
      change occurs whether or not the eyes receive input from the circadian clock, but
      it is eliminated in eyes maintained in the dark. Thus, it is regulated by light
      and darkness, not by the circadian clock, with light stimulating an increase in
      opsin mRNA levels. The rise in opsin mRNA levels observed under natural
      illumination was seasonal; it occurred during the summer but not the spring and
      fall. However, a significant increase in opsin mRNA levels could be achieved in
      the fall by exposing lateral eyes to 3 h of natural illumination followed by 9 h
      of artificial light. The diurnal regulation of opsin mRNA levels contrasts
      sharply with the circadian regulation of visual arrestin mRNA levels (Battelle et
      al., 2000). Thus, in Limulus, distinctly different mechanisms regulate the levels
      of mRNA encoding two proteins critical for the photoresponse.

PMID- 14977332
TI  - Modulation of the components of the rat dark-adapted electroretinogram by the
      three subtypes of GABA receptors.
AB  - The separate components of the dark-adapted electroretinogram (ERG) are believed
      to reflect the electric activity of neurones in both the inner and the outer
      layers of the retina, although their precise origin still remains unclear. The
      purpose of this study was to examine whether selective blockage or stimulation of
      the different subtypes of GABA receptors might help further elucidate the
      cellular origin of the components of the dark-adapted ERG. The rat retina is of
      interest since the localization and physiology of GABA receptors in that retina
      have been examined in great detail. GABA agonists and antagonists, known to
      affect the responses of neurons in the inner plexiform layer, were injected into
      the vitreous of one eye while ERG responses evoked by flashes of white light were
      recorded. GABA and the GABAa agonist isoguvacine completely removed the
      oscillatory potentials (OPs) and reduced the amplitude of the a- and b-waves.
      TPMPA, a GABAC antagonist, reduced the a- and b-waves but had no significant
      effect on the OPs. Baclofen, a GABAb agonist, reduced the amplitude of the a- and
      b-waves, without having any effects on the amplitude of the OPs. The GABAb
      antagonist CGP35348 increased the amplitudes of the a- and b-wave without having
      an effect on the amplitudes of the OPs. The GABAb receptor ligands had
      significant and opposite effect on the latency of the OPs. These results indicate
      that retinal neurons, presumably a subpopulation of amacrine cells, that have
      GABAb receptors are not the source of the OPs of the ERG, although they may
      modulate these wavelets in some manner, while contributing to the generation of
      the dark-adapted a- and b-waves. OPs are modified by stimulation of GABAa
      receptors, and the a- and b-waves by stimulation of all GABA receptor subtypes.

PMID- 14977333
TI  - Visual resolution with epi-retinal electrical stimulation estimated from
      activation profiles in cat visual cortex.
AB  - Blinds with receptor degeneration can perceive localized phosphenes in response
      to focal electrical epi-retinal stimuli. To avoid extensive basic stimulation
      tests in human patients, we developed techniques for estimating visual spatial
      resolution in anesthetized cats. Electrical epi-retinal and visual stimulation
      was combined with multiple-site retinal and cortical microelectrode recordings of
      local field potentials (LFPs) from visual areas 17 and 18. Classical visual
      receptive fields were characterized for retinal and cortical recording sites
      using multifocal visual stimulation combined with stimulus-response cross
      correlation. We estimated visual spatial resolution from the size of the cortical
      activation profiles in response to single focal stimuli. For comparison, we
      determined activation profiles in response to visual stimuli at the same retinal
      location. Activation profiles were single peaked or multipeaked. In multipeaked
      profiles, the peak locations coincided with discontinuities in cortical
      retinotopy. Location and width of cortical activation profiles were distinct for
      retinal stimulation sites. On average, the activation profiles had a size of 1.28
      +/- 0.03 mm cortex. Projected to visual space this corresponds to a spatial
      resolution of 1.49 deg +/- 0.04 deg visual angle. Best resolutions were 0.5 deg
      at low and medium stimulation currents corresponding to a visus of 1/30. Higher
      stimulation currents caused lower spatial, but higher temporal resolution (up to
      70 stimuli/s). In analogy to the receptive-field concept in visual space, we
      defined and characterized electrical receptive fields. As our estimates of visual
      resolutions are conservative, we assume that a visual prosthesis will induce
      phosphenes at least at this resolution. This would enable visuomotor
      coordinations and object recognition in many indoor and outdoor situations of
      daily life.

PMID- 14977334
TI  - Activation of glutamate transporters in rods inhibits presynaptic calcium
      currents.
AB  - We found that L-glutamate (L-Glu) inhibits L-type Ca2+ currents (ICa) in rod
      photoreceptors. This inhibition was studied in isolated rods or rods in retinal
      slices from tiger salamander using perforated patch whole cell recordings and Cl(
      )-imaging techniques. Application of L-Glu inhibited ICa by approximately 20% at
      0.1 mM and approximately 35% at 1 mM. L-Glu also produced an inward current that
      reversed around ECl. The metabotropic glutamate receptor (mGluR) agonists t-ADA
      (Group I), DCG-IV (Group II), and L-AP4 (Group III) had no effect on ICa.
      However, the glutamate transport inhibitor, TBOA (0.1 mM), prevented L-Glu from
      inhibiting ICa. D-aspartate (D-Asp), a glutamate transporter substrate, also
      inhibited ICa with significantly more inhibition at 1 mM than 0.1 mM. Using Cl
      imaging, L-Glu (0.1-1 mM) and D-Asp (0.1-1 mM) were found to stimulate a Cl-
      efflux from terminals of isolated rods whereas the ionotropic glutamate receptor
      agonists NMDA, AMPA, and kainate and the mGluR agonist, 1S,3R-ACPD, did not.
      Glutamate-evoked Cl- effluxes were blocked by the glutamate transport inhibitors
      TBOA and DHKA. Cl- efflux inhibits Ca2+ channel activity in rod terminals
      (Thoreson et al. (2000), Visual Neuroscience 17, 197). Consistent with the
      possibility that glutamate-evoked Cl- efflux may play a role in the inhibition,
      reducing intraterminal Cl- prevented L-Glu from inhibiting ICa. In summary, the
      results indicate that activation of glutamate transporters inhibits ICa in rods
      possibly as a consequence of Cl- efflux. The neurotransmitter L-Glu released from
      rod terminals might thus provide a negative feedback signal to inhibit further L
      Glu release.

PMID- 14977335
TI  - Development of contour integration in macaque monkeys.
AB  - Studies of visual development show that basic metrics of visual development such
      as spatial resolution develop over the first 6-9 months in monkeys and over the
      first 6 or so years in humans. However, more complex visual functions may develop
      over different, or more protracted, time courses. To address the question of
      whether global perceptual processing is linked to or otherwise dependent on the
      development of basic spatial vision, we studied the development of contour
      integration, a global perceptual task, in comparison to that of grating acuity in
      macaque monkeys. We find that contour integration develops substantially later
      than acuity. Contour integration begins to develop at 5-6 months, near the time
      that acuity development is complete and continues to mature well into the second
      postnatal year. We discuss this later development in terms poor central
      efficiency and consider the relevant anatomy and physiology of the developing
      visual system. We conclude that contour integration is not likely to be limited
      by the same mechanisms that are permissive to acuity development, and may instead
      reflect the emergence of function central to V1.

PMID- 14977336
TI  - Contour integration in amblyopic monkeys.
AB  - Amblyopia is characterized by losses in a variety of aspects of spatial vision,
      such as acuity and contrast sensitivity. Our goal was to learn whether those
      basic spatial deficits lead to impaired global perceptual processing in
      strabismic and anisometropic amblyopia. This question is unresolved by the
      current human psychophysical literature. We studied contour integration and
      contrast sensitivity in amblyopic monkeys. We found deficient contour integration
      in anisometropic as well as strabismic amblyopic monkeys. Some animals showed
      poor contour integration in the fellow eye as well as in the amblyopic eye.
      Orientation jitter of the elements in the contour systematically decreased
      contour-detection ability for control and fellow eyes, but had less effect on
      amblyopic eyes. The deficits were not clearly related to basic losses in contrast
      sensitivity and acuity for either type of amblyopia. We conclude that abnormal
      contour integration in amblyopes reflects disruption of mechanisms that are
      different from those that determine acuity and contrast sensitivity, and are
      likely to be central to V1.

PMID- 14977337
TI  - Postoperative cognitive deficits: more questions than answers.

PMID- 14977338
TI  - Acid aspiration prophylaxis in obstetrics in France: a comparative survey of 1998
      vs. 1988 French practice.
AB  - BACKGROUND AND OBJECTIVE: To survey French anaesthetic practice regarding acid
      aspiration prophylaxis and compare it with an earlier survey. METHODS: A
      confidential questionnaire was sent to all 800 maternity units in France to
      assess three major topics: (a) drugs used for pharmacological prophylaxis; (b)
      regional anaesthesia for labour and Caesarean section and (c) techniques used for
      general anaesthesia and endotracheal intubation. RESULTS: Two-hundred-and-two
      units responded. Pharmacological prophylaxis was regularly used for labouring
      women in 78% of the responding units in 1998 (compared with 63% in 1988, P <
      0.05). Antacid drug use before Caesarean section had increased from 75% in 1988
      to 97% in 1998 (P < 0.05). General anaesthesia was used for Caesarean section by
      less than 2% of responding units (vs. 21% in 1988, P < 0.05). In contrast, there
      was little change in the use of endotracheal intubation for instrumental delivery
      (53% vs. 50%) or manual removal of the placenta (15% vs. 16%) between 1988 and
      1998. The use of cricoid pressure increased significantly during the 10 yr period
      (50% vs. 88%, P < 0.05) and the technique was correctly described by 80% of the
      responding units (vs. 50%, P < 0.05). Similarly, the use of succinylcholine
      increased significantly from 25% (1988) to 479 (1998) (P < 0.05). CONCLUSIONS:
      There was a significant overall improvement of French practice regarding acid
      aspiration prophylaxis in obstetrics. However, the complete prophylaxis strategy
      is still not used in every patient emphasizing the need for continuing medical
      education.

PMID- 14977339
TI  - Effects of remifentanil and fentanyl on intraocular pressure during the
      maintenance and recovery of anaesthesia in patients undergoing non-ophthalmic
      surgery.
AB  - BACKGROUND AND OBJECTIVE: To compare the effects of remifentanil and fentanyl on
      intraocular pressure during the maintenance and recovery of anaesthesia in
      patients undergoing elective non-ophthalmic surgery. METHODS: Thirty-two patients
      (ASA I-II) were randomized into two groups to receive either a continuous
      infusion of remifentanil (0.25-0.5 microg kg(-1) min(-1), n =16, Group R) or an
      intermittent bolus of fentanyl (2-5 microg kg(-1), n = 16, Group F) during the
      maintenance of anaesthesia. For the induction of anaesthesia, Group R received
      remifentanil 1 microg kg(-1) and Group F received fentanyl 2 microg kg(-1); both
      groups then received propofol 2 mg kg(-1) with vecuronium 0.1 mg kg(-1).
      Anaesthesia in both groups was maintained with a continuous infusion of propofol
      4-8 mg kg(-1) h(-1). Ventilation of the lungs was controlled to a constant end
      tidal PCO2 of 4.7-5.4 kPa. Blood pressure, electrocardiography, heart rate and
      oxygen saturation were monitored throughout anaesthesia. Intraocular pressure was
      determined before surgery, during the maintenance of anaesthesia, 2 min after
      emergence and in the recovery room using a Perkins hand-held applanation
      tonometer by an ophthalmologist blinded to the anaesthetic technique. RESULTS:
      After induction of anaesthesia, a significant decrease in intraocular pressure in
      the remifentanil group from 13.6 +/- 2.6 to 7.1 +/- 3.1 mmHg (P < 0.001) and in
      the fentanyl group from 13.7 +/- 2.2 to 9.7 +/- 3.4 mmHg (P < 0.001) was observed
      and maintained during anaesthesia. Thirty minutes after the end of anaesthesia,
      intraocular pressure returned to baseline values in both groups (remifentanil:
      13.9 +/- 2.8 mmHg, P = 0.28; fentanyl: 13.6 +/- 2.3 mmHg, P = 0.59). The
      intraocular pressure and haemodynamic variables did not differ significantly
      between the two groups (intraocular pressure, P = 0.7327; blood pressure, P =
      0.1295; heart rate, P = 0.8601). CONCLUSIONS: Remifentanil maintains intraocular
      pressure at an equally reduced level compared with fentanyl.

PMID- 14977340
TI  - Factors independently associated with increased risk of pain development after
      ophthalmic surgery.
AB  - BACKGROUND AND OBJECTIVE: Little has been documented about the development of
      pain after ophthalmic surgery. This study was designed to assess the incidence
      and severity of postoperative pain following ophthalmic surgery, and to identify
      key factors independently associated with development of such pain. METHODS: In a
      prospective, observational cohort study, 500 patients undergoing elective
      ophthalmic surgery were examined by assessing numerical analogue scales and
      analgesic requirements. RESULTS: Depending on anatomical location of surgery,
      operations could be classified into creating 'more severe' or 'less severe pain'.
      Patients undergoing posterior segment, corneal and muscle surgery exhibited the
      highest numerical analogue scale scores (risk ratio 4.5, 95% CI 3.01-6.79, P <
      0.0001). Anterior segment surgery, which per se did not create much pain,
      resulted in significantly more pain when performed under general anaesthesia
      compared to regional anaesthesia (risk ratio 6.52, 95% CI 2.33-18.2, P < 0.0001).
      No other factors independently associated with an increased risk of developing
      serious postoperative pain could be identified. CONCLUSIONS: Patients undergoing
      certain ophthalmic operations, especially if performed under general anaesthesia,
      are more likely to experience serious postoperative pain.

PMID- 14977341
TI  - Fast-track eligibility, costs and quality of recovery after intravenous
      anaesthesia with propofol-remifentanil versus balanced anaesthesia with
      isoflurane-alfentanil.
AB  - BACKGROUND AND OBJECTIVE: The randomized, patient- and observer-blinded study was
      performed in 120 patients undergoing ear, nose and throat surgery to test the
      hypothesis that intravenous anaesthesia with propofol-remifentanil when compared
      with a balanced anaesthesia technique using isoflurane-alfentanil improves the
      speed of recovery, minimizes postoperative side-effects and, thus, leads to an
      improved quality of recovery without increasing total costs. METHODS: The total
      costs for each anaesthesia technique were calculated considering drug acquisition
      costs, personnel costs for the additional time spent in the operating room and
      the postanaesthesia care unit until fast-tracking eligibility, and the costs to
      treat the side-effects during and after operation. RESULTS: The times from the
      end of surgery to tracheal extubation and the time until leaving the operating
      room were not different between the two groups. However, more patients receiving
      intravenous anaesthesia (80 versus 49%) were eligible for fast tracking and thus
      could bypass the recovery room. This was associated with an average cost saving
      of 6.00 euros per patient. However, intravenous anaesthesia was associated with
      higher total costs (89 euros versus 78 euros) mainly because of higher
      acquisition costs of the anaesthetics (34.60 euros versus 16.50 euros). There was
      no difference in the quality of recovery as measured by a Quality of Recovery
      score and patient satisfaction between the two groups. CONCLUSIONS: The higher
      acquisition costs of the intravenous anaesthetics propofol and remifentanil
      cannot be compensated for by improved speed of recovery. This anaesthesia
      technique is more cost intensive than balanced anaesthesia using isoflurane and
      alfentanil.

PMID- 14977342
TI  - Cost-effectiveness and high patient satisfaction in the elderly: sevoflurane
      versus propofol anaesthesia.
AB  - BACKGROUND AND OBJECTIVE: The use of propofol compared with isoflurane is
      associated with improved patient comfort and decreased costs. However, as the
      cost saving, the quicker recovery time and patient comfort may not be evident if
      sevoflurane is substituted for isoflurane; these two anaesthetic agents were
      analysed in elderly patients. METHODS: In a prospective randomized study, 96
      patients undergoing elective ophthalmic surgery received either total intravenous
      anaesthesia with propofol (Group P), propofol for induction and sevoflurane for
      maintenance (Group P/S) or sevoflurane for inhalation induction and maintenance
      (Group S). Analyses focussed on haemodynamics, the quality of recovery, and the
      costs for the anaesthetic and the entire procedure. RESULTS: Bradycardia or
      hypotension, mainly registered in Groups P and P/S, did not influence patients'
      recovery. In Group S, postoperative nausea and vomiting occurred frequently, and
      50% of patients complained of discomfort during induction. In Group P/S, the
      costs for anaesthetics and total costs were lower than those in Groups P and S.
      CONCLUSIONS: Propofol- and sevoflurane-based maintenance of anaesthesia were
      similar with regard to patient comfort and recovery in the elderly. Cost analysis
      revealed that it was less expensive to use propofol for induction and sevoflurane
      for maintenance than to use either propofol or sevoflurane as sole agents for
      anaesthesia.

PMID- 14977343
TI  - Management of unanticipated difficult intubation: a survey of current practice in
      the Oxford region.
AB  - BACKGROUND AND OBJECTIVE: Unanticipated difficulty in tracheal intubation in an
      anaesthetized patient has always been a cause of concern to anaesthesiologists.
      This difficulty may lead to morbidity and mortality. This survey was carried out
      to determine the technique commonly favoured in centres in the Oxford region in
      the UK for the management of unanticipated difficult intubation. METHODS: We
      conducted a clinical scenario-based questionnaire survey of 181
      anaesthesiologists in the Oxford region. In this scenario, difficulty in
      endotracheal intubation is recognized only after induction of anaesthesia. A
      number of options were available to deal with this situation. We used this
      scenario as a tool to gain insight into the training and the training needs of
      anaesthesiologists at various levels of training. RESULTS: Of the 181
      questionnaires sent, we received 143 (79%) completed replies. The vast majority
      (141/143 (99%)) of anaesthesiologists would use a gum-elastic bougie together
      with head and neck positioning and optimal external laryngeal manipulation to
      gain the best attempt at intubation. If intubation still failed, overall 129/143
      (90%) had a back-up plan, while 14/143 (10%) had no plan. Flexible fibreoptic
      techniques were more commonly planned by 92/143 (64%) anaesthesiologists compared
      to blind techniques which were less commonly planned by 37/143 (26%)
      anaesthesiologists. Differences in choice of technique among anaesthesiologists
      in teaching and district general hospitals were not significant (P = 0.87).
      Overall, trainees were less likely to choose fibreoptic techniques compared to
      consultants (P = 0.0009) and would use blind techniques or ask a more experienced
      colleague to take over. The main reason for the choice was previous experience
      with the technique. CONCLUSIONS: Although fibreopric techniques were most
      commonly planned, these were less often chosen by trainees than consultants due
      to lack of experience/training, while unavailability of intubating laryngeal mask
      airway (Intavent) was an additional issue precluding its use as an adjunct to
      intubation.

PMID- 14977344
TI  - Difficult airway equipment in departments of emergency medicine in Ireland:
      results of a national survey.
AB  - BACKGROUND AND OBJECTIVE: Adverse effects associated with difficult airway
      management can be catastrophic and include death, brain injury and myocardial
      injury. Closed-malpractice claims have shown prolonged and persistent attempts at
      endotracheal intubation to be the most common situation leading to disastrous
      respiratory events. To date, there has been no evaluation of the types of
      difficult airway equipment currently available in Irish departments of emergency
      medicine. The objective of this survey was to identify the difficult airway
      equipment available in Irish departments of emergency medicine. METHODS:
      Departments of emergency medicine in the Republic of Ireland with at least one
      dedicated Emergency Medicine consultant were surveyed via telephone. RESULTS: All
      of the departments contacted held at least one alternative device on site for
      both ventilation and intubation. The most common alternative ventilation device
      was the laryngeal mask airway (89%). The most common alternative intubating
      device was the surgical airway device (100%). CONCLUSIONS: Irish departments of
      emergency medicine compare well with those in the UK and USA, when surveyed
      concerning difficult airway equipment. However, we believe that this situation
      could be further improved by training inexperienced healthcare providers in the
      use of the laryngeal mask airway and intubating laryngeal mask airway, by placing
      greater emphasis on the ready availability of capnography and by the increased
      use of portable difficult airway storage units.

PMID- 14977345
TI  - Assessing fluid responsiveness by stroke volume variation in mechanically
      ventilated patients with severe sepsis.
AB  - BACKGROUND AND OBJECTIVE: Our hypothesis was that stroke volume variation during
      mechanical ventilation of the lungs would allow accurate prediction and
      monitoring of changes in cardiac index in response to fluid loading in patients
      with severe sepsis. METHODS: This was a prospective clinical study in a
      university hospital. Ten mechanically ventilated patients with severe sepsis or
      septic shock were given fluid loading with 500 mL 10% hydroxyethylstarch 200/0.5
      over 30 min. Before and after fluid loading pulmonary arterial occlusion pressure
      and central venous pressure were measured. Intrathoracic blood volume index,
      stroke volume variation and cardiac index were measured by the transpulmonary
      thermodilution technique. After verifying normal distribution of the data
      (skewness < 1.0) the paired t-test was used for statistical analysis. RESULTS:
      After fluid loading stroke volume variation decreased significantly, whereas
      central venous pressure, pulmonary arterial occlusion pressure, intrathoracic
      blood volume index and cardiac index increased significantly. Changes of cardiac
      index in response to fluid loading were correlated to baseline values of stroke
      volume variation (r = 0.64, P = 0.02) and intrathoracic blood volume index (r = 
      0.73, P = 0.009). Changes in cardiac index were significantly correlated to
      percentage changes in stroke volume variation (r = -0.65, P < 0.001) and changes
      in intrathoracic blood volume index (r = 0.52, P = 0.002), whereas changes in
      cardiac index revealed no significant correlation to changes in central venous
      pressure (r = 0.28, P = 0.07) and changes in pulmonary arterial occlusion
      pressure (r = 0.29, P = 0.06). CONCLUSIONS: Measuring stroke volume variation may
      be a useful way of guiding fluid therapy in ventilated patients with severe
      sepsis because it allows estimation of preload and prediction of cardiac index
      changes in response to fluid loading.

PMID- 14977346
TI  - Xenon modulates neutrophil adhesion molecule expression in vitro.
AB  - BACKGROUND AND OBJECTIVE: Xenon reduces the infarct size after regional ischaemia
      in the rabbit heart in vivo, but the underlying mechanisms are unknown. Since
      adhesion molecules on neutrophils are closely involved in the pathophysiology of
      ischaemia/reperfusion injury and modulation of neutrophil function, we
      investigated the effect of xenon on neutrophil adhesion molecule expression in
      vitro. METHODS: Freshly isolated neutrophils were incubated with 30% or 60% xenon
      for 60 min. In unstimulated and after stimulation with either N-formyl-methionyl
      leucyl-phenylalanine or phorbol-12-myristate-13-acetate neutrophil surface
      expression of PSGL-1, L-selectin, CD11a and CD11b were measured by flow
      cytometry. RESULTS: At both concentrations, xenon reduced the surface expression
      of PSGL-1 by 10% (P < 0.05), and of L-selectin by 15% (P < 0.05) in the 60% xenon
      group. Furthermore, N-formyl-methionyl-leucyl-phenylalanine activated neutrophils
      showed an increased removal of L-selectin from the neutrophil surface following
      incubation with xenon (30% compared to controls, P < 0.05). Neutrophil beta2
      integrin expression was not altered by xenon. CONCLUSIONS: Xenon increases the
      removal of the selectins PSGL-1 and L-selectin from the neutrophil surface in
      vitro. Since both selectins are involved in the initial contact between
      neutrophils and endothelial cells, xenon may affect neutrophil adhesion to
      endothelium during ischaemia/reperfusion injury. However, because the beta2
      integrin expression was unaffected by xenon, further investigations are required
      to clarify whether xenon may modulate neutrophil transmigration through
      endothelial cells in vivo.

PMID- 14977347
TI  - Release of S(+) enantiomers in breath samples after anaesthesia with isoflurane
      racemate.
AB  - BACKGROUND AND OBJECTIVE: Isoflurane is a chiral volatile anaesthetic, routinely
      administered as racemate. It has a low metabolic rate and is mostly eliminated
      via respiration. In blood samples, S(+) enantiomers are found in greater
      proportion in the days immediately after administration of isoflurane racemate
      whereas the ratio in breath samples is unknown. METHODS: Breath and blood samples
      were drawn immediately after recovery and daily up to 19 days after operation
      from patients undergoing anaesthesia with isoflurane racemate. The percentage of
      isoflurane enantiomer was determined by gas chromatography mass spectrometry in
      blood and thermodesorption gas chromatography mass spectrometry in breath
      samples. RESULTS: In breath samples, there were significant differences in S(+)
      enantiomers at all time points compared to the racemate. During the early
      postoperative phase, the percentage of S(+) enantiomers were significantly
      enhanced whereas 5 days after surgery predominantly R(-) enantiomers (50.41%)
      were detected in the breath samples. Also in blood samples a statistical
      significant accumulation of the S(+) enantiomer was noted between days 1 and 5
      compared to isoflurane racemate blood control. S(+) enantiomers were
      significantly higher in blood compared to breath samples and was most evident on
      the third day after surgery (51.43%). CONCLUSIONS: During the first days after
      application of isoflurane racemate, the percentage of S(+) enantiomers are higher
      in breath and blood samples of patients. We suggest that resorption and/or
      redistribution of enantiomers are responsible for the different kinetics of
      isoflurane enantiomers.

PMID- 14977348
TI  - Similar susceptibility to halothane, caffeine and ryanodine in vitro reflects
      pharmacogenetic variability of malignant hyperthermia.
AB  - BACKGROUND AND OBJECTIVE: To analyse the use of standardized application of
      ryanodine for in vitro muscle contracture testing to define cut-off values
      separating malignant hyperthermia susceptible from malignant hyperthermia
      negative subjects. Furthermore, we compared the results of in vitro muscle
      contracture tests following the halothane, caffeine and ryanodine challenges.
      METHODS: In 113 subjects, halothane, caffeine and ryanodine muscle-contracture
      tests were performed according to the protocol of the European Malignant
      Hyperthermia Group. RESULTS: Malignant hyperthermia susceptible subjects (n = 77)
      had significantly shorter onset times in the ryanodine in vitro muscle
      contracture test (1 micromol ryanodine) compared with malignant hyperthermia
      negative subjects (n = 36), median 4.8 vs. 20.1 min, respectively, without any
      influence of age or gender. The best cut-off value was 10 min (sensitivity 0.78
      and specificity 0.94, respectively). Shorter cut-off values had greater
      specificity, but lower sensitivity. Groups could not be separated without an
      overlap. In susceptible subjects, we found a correlation between onset time and
      threshold concentrations for halothane and caffeine (p = 0.47 and 0.52,
      respectively). In addition, muscle bundles with high susceptibility to halothane
      and caffeine also showed high susceptibility to ryanodine. CONCLUSIONS: The
      ryanodine in vitro muscle-contracture test confirmed the malignant hyperthermia
      status that was determined using the halothane and caffeine in vitro muscle
      contracture tests. Due to an overlap between the two groups, discrimination
      ability was not always perfect and short cut-off values with higher specificity
      had reduced sensitivity and vice versa. The correlation of contractures following
      the halothane, caffeine and ryanodine challenges points towards a similar
      individual pharmacogenetic effect rather than a specific, different
      pharmacological action between the three agents.

PMID- 14977349
TI  - Effects on left ventricular performance of changes in cardiac loading conditions
      depend on 'relative load'.

PMID- 14977350
TI  - Anaesthesiologists do not have attention- and memory-related cognitive
      dysfunctions in comparison with matched physicians.

PMID- 14977351
TI  - Anaesthetic management in a case of Kabuki syndrome.

PMID- 14977352
TI  - Clinical assessment of use of the Airway Management Device (AMD).

PMID- 14977353
TI  - Emerging roles of targeted small molecule protein-tyrosine kinase inhibitors in
      cancer therapy.
AB  - Targeted protein-tyrosine kinase inhibitors (PTKIs) comprise a new, rapidly
      evolving class of low molecular weight anticancer drugs. Two members of this
      class, imatinib (Gleevec) and gefitinib (Iressa), are currently approved for
      market use in the United States. This review discusses the scientific history
      behind these two PTKI drugs, including the role of the targeted kinase in cancer
      etiology, the biochemistry of selective inhibition, the evaluation of clinical
      efficacy, and the mechanisms whereby drug resistance has emerged. Other PTKIs
      undergoing clinical evaluation are also described, including epidermal growth
      factor receptor kinase inhibitors (erlotinib, PKI166, and CI-1033) and PTKIs
      designed to disrupt tumor vascularization (SU5416, SU6668, SU11248, PTK787, and
      ZD6474). How might one apply current knowledge to the efficient development of
      new agents that would target as-yet-unexploited oncogenic PTKs such as chimeric
      anaplastic leukemia kinases or Janus kinases? Ideally, the targets should contain
      structurally distinct drug interaction epitopes, although it is not necessary
      that these epitopes be unique to a single target, because effective drugs may
      inhibit multiple kinases involved in an oncogenic process. Oral availability is a
      highly desirable feature because daily oral administration can maintain a
      sustained efficacious plasma concentration, whereas intermittent parenteral
      administration may not. Perhaps most importantly, one must verify the presence of
      an appropriate molecular target on a case-by-case basis before selecting a
      patient for PTKI therapy. Thus, the development of molecularly targeted
      diagnostic tools will be crucial to the ultimate success of molecularly targeted
      PTKI therapy.

PMID- 14977354
TI  - Inhibition of angiogenesis by salmosin expressed in vitro.
AB  - Recently, salmosin, a novel snake venom-derived disintegrin containing the Arg
      Gly-Asp (RGD) sequence, was reported to be both antiangiogenic and
      antitumorigenic. The antitumor activity was substantiated by in vivo
      administration of recombinant salmosin into mice bearing tumors. However, it was
      difficult to prepare functionally active recombinant salmosin and to maintain a
      therapeutically effective concentration of the protein in the circulatory system
      by daily injections. Hence, we have suggested that salmosin gene transfer
      mediated by cationic liposomes may be a practical alternative for cancer
      treatment. Plasmids encoding the salmosin gene were constructed and then
      transferred by means of cationic liposomes into transformed human embryonic
      kidney (HEK) 293 cells. The transfected genes were able to produce functionally
      active salmosin proteins in vitro. In fact, the expressed salmosin remarkably
      inhibited proliferation of bovine capillary endothelial (BCE) cells and
      effectively inhibited the migration of highly metastatic B16BL6 mouse melanoma
      cells. Neovascularization in chick chorio-allantoic membranes (CAM) and in
      Matrigel implanted subcutaneously into mice was greatly inhibited in the presence
      of the expressed salmosin. Based on these experimental results, we suggest that
      the antitumor effect induced by salmosin gene transfection may be due to the
      antiangiogenic activity of the expressed salmosin proteins.

PMID- 14977355
TI  - Hydroxyurea-induced apoptosis in an EBV-immortalized lymphoblastoid cell line.
AB  - Hydroxyurea (HU) is an inhibitor of nucleotide synthesis extensively used to
      control the chronic phase of myeloid leukemia. This antimetabolite has been
      employed in the clinic for several decades but in recent years the leukemogenic
      potential of HU has been suspected. In the present study, a B-lymphoblastoid cell
      line transformed by the Epstein-Barr virus was used to investigate the apoptotic
      effects of HU and delineate some of the molecular pathways implicated in the
      cytotoxic action. The cell line, characterized by immunophenotyping, cytogenetic
      and fluorescence in situ hybridization (FISH) studies, showed no chromosomal
      abnormalities, even after a prolonged exposure to HU. Different flow cytometry
      assays were used to measure HU-induced impairment of the cell cycle, inhibition
      of DNA synthesis, and the occurrence of apoptosis. The treatment with HU leads to
      the appearance of a hypo-diploid DNA content peak (sub-G1) characteristic of the
      apoptotic cell population. The drug also induces a cell block in S phase as
      measured by 5-bromo-2'-deoxyuridine (BrdU) incorporation. Inhibition of DNA
      synthesis precedes induction of apoptosis by HU. A drug-induced loss of plasma
      membrane asymmetry was characterized by flow cytometry using annexin V-FITC to
      stain phosphatidylserine residues. The implication of the antiapoptotic protein
      Bcl-2 and the tumor suppressor p53 in the development of HU-mediated apoptosis
      was also evidenced. The drug appears to promote cell death by regulating the
      expression levels of these two proteins. Different criteria define the apoptotic
      response of the lymphoblastoid cells to the treatment with HU. However, the
      extent of drug-induced cell death is limited, and no DNA fragmentation and no
      activation of the caspase cascade was observed in this model. Beyond the specific
      interest in HU-induced apoptosis, the work reported here illustrates the utility
      of the EBV immortalization process to investigate the pharmacological activity of
      specific drugs from clinical samples.

PMID- 14977356
TI  - Synthesis and in vitro cytotoxicity studies of novel L-tryptophan-polyamide
      conjugates and L-tryptophan dimers linked with aliphatic chains and polyamides.
AB  - The synthesis and biological evaluation of novel L-tryptophan pyrrole, imidazole
      polyamide conjugates (16-21), L-tryptophan-glycosylated pyrrole polyamide
      conjugates (28-30), L-tryptophan dimers (37-42) with straight carbon links of
      varying length, and L-tryptophan dimers (68-73) linked with pyrrole and imidazole
      polyamide from both sides by a flexible methylene chain of variable length are
      described. The compounds were prepared with varying numbers of pyrrole- and/or
      imidazole-containing polyamides and glycosylated pyrrole polyamides to determine
      the structural requirements for optimal in vitro antitumor activity. The
      compounds listed in Table 1 have been evaluated in a three cell line, one dose
      primary anticancer assay. The compounds listed in Table 2 have been evaluated
      against nine panels of 60 human cancer cell lines including leukemia, non-small
      cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal
      cancer, prostate cancer, and breast cancer. It is observed from the initial
      cytotoxic data (Table 1) that compounds 16-19, 28-30, 68-69, and 71-73 have
      varying cytotoxic potencies against the three cancer cell lines. It is also
      observed, from the biological data from Table 2 for compounds 20-21, 37-42, and
      70 against the 60 different tumor cells, that the L-tryptophan dimers 37-42
      linked by a different number of carbon chains are more active than the L
      tryptophan dimers linked by pyrrole or imidazole polyamides. The cytotoxic
      potency in tryptophan dimers, linked by a different number of carbon atoms
      increased the number of carbons between the two L-tryptophan rings.

PMID- 14977357
TI  - Low iron diet and parenteral cadmium exposure in pregnant rats: the effects on
      trace elements and fetal viability.
AB  - The effects of latent iron deficiency combined with parenteral subchronic or
      acute cadmium exposure during pregnancy on maternal and fetal tissue distribution
      of cadmium, iron and zinc, and on fetal viability were evaluated. Timed-pregnant
      Sprague-Dawley rats were fed on semisynthetic test diets with either high iron
      (240 mg kg) or low iron (10 mg kg), and concomitantly exposed to 0, 3 or 5 mg
      cadmium (as anhydrous CdCl2) per kilogram body weight. Animals were exposed to
      cadmium from gestation day 1 through 19 by subcutaneously implanted mini pumps
      (Subchronic exposure) or on gestation day 15 by a single subcutaneous injection
      (Acute exposure). All rats were killed on gestation day 19. Blood samples,
      selected organs and fetuses were removed and prepared for element analyses by
      atomic absorption spectrometry. Low iron diet caused decreases in maternal body
      weight, maternal and fetal liver weights, placental weights and tissue iron
      concentrations. By cadmium exposure, both subchronic and acute, tissue cadmium
      concentrations were increased and the increase was dose-related, maternal liver
      and kidney zinc concentrations were increased, and fetal zinc concentration was
      decreased. Cadmium concentration in maternal liver was additionally increased by
      low iron diet. Acute cadmium exposure caused lower maternal body and organ
      weights, high fetal mortality, and decreased fetal weights of survivors. In
      conclusion, parenteral cadmium exposure during pregnancy causes perturbations in
      essential elements in maternal and fetal compartments. Acute cadmium exposure in
      the last trimester of gestation poses a risk for fetal viability especially when
      combined with low iron in maternal diet.

PMID- 14977358
TI  - Regulation of p27(Kip1) by intracellular iron levels.
AB  - Enhanced intracellular iron levels are essential for proliferation of mammalian
      cells. If cells have entered S phase when iron is limiting, an adequate supply of
      deoxynucleotides cannot be maintained and the cells arrest with incompletely
      replicated DNA. In contrast, proliferating cells that are not in S phase, but
      have low iron pools, arrest in late G1. In this report the mechanism of iron
      dependent G1 arrest in normal fibroblasts was investigated. Cells were
      synchronized in G0 by contact inhibition and serum deprivation. Addition of serum
      caused the cells to re-enter the cell cycle and enter S phase. However, if the
      cells were also treated with the iron chelator deferoxamine, S phase entry was
      blocked. This corresponded to elevated levels of the cyclin dependent kinase
      inhibitor p27(Kip1) and inhibition of CDK2 activity. Expression of other cell
      cycle regulatory proteins was not affected, including the induction of cyclins D1
      and E. When the quiescent serum starved cells were supplemented with a readily
      usable form of iron in the absence of serum or any other growth factors, a
      significant population of the cells entered S phase. This was associated with
      downregulation of p27(Kip1) and increased CDK2 activity. Using an IPTG-responsive
      construct to artificially raise p27(Kip1) levels blocked the ability of iron
      supplementation to promote S phase entry. Thus it appears that p27(Kip1) is a
      mediator of G1 arrest in iron depleted Swiss 3T3 fibroblasts. We propose that
      this is part of an iron-sensitive checkpoint that functions to ensure that cells
      have sufficient iron pools to support DNA synthesis prior to entry into S phase.

PMID- 14977359
TI  - Uptake of chromium(III) and chromium(VI) compounds in the yeast cell structure.
AB  - The study presented in this article investigated the influence of different
      Cr(III) and Cr(VI) compounds in the cultivation medium on the uptake and
      localization of chromium in the cell structure of the yeast Candida intermedia.
      The morphology of the yeast cell surface was observed by the scanning electron
      microscopy. Results demonstrated that the growth inhibitory concentration of
      Cr(III) in the cultivation medium induced changes in the yeast cell shape and
      affected the budding pattern, while inhibitory concentration of Cr(VI) did not
      cause any visible effects on morphological properties of the yeast cells. The
      amount of total accumulated chromium in yeast cells and the distribution of
      chromium between the yeast cell walls and spheroplasts were determined by atomic
      absorption spectroscopy. No significant differences were found neither in total
      chromium accumulation nor in the distribution of chromium in yeast cell walls and
      spheroplasts between the two of Cr(VI) compounds. Conversely, substantial
      differences between Cr(III) compounds were demonstrated in the total uptake as
      well as the localization of chromium in yeast cells.

PMID- 14977360
TI  - Effect of the manganese ion on human alpha3/4 fucosyltransferase III activity.
AB  - The effect of manganese and other divalent cations on the activity of a soluble
      recombinant form of human alpha3/4 fucosyltransferase III (SFT3) expressed in
      Spodoptera frugiperda (Sf9) insect cells was studied. SFT3 was active in the
      absence of divalent cations with an optimum pH of 4.5. In the absence of Mn2+
      increasing the pH from 4.5 to 7.0 caused a decrease in the affinity of SFT3 for
      the acceptor Galbeta3GlcNAcO(CH2)3NHCO(CH2)5NH-biotin, as monitored by the 4-fold
      increase in the apparent KM value (0.9 to 3.3 mM). At pH 7.0, the addition of
      Mn2+ activated the enzyme and caused an increase in the affinity of SFT3 for the
      acceptor, as monitored by the 5-fold decrease of the apparent KM value (3.3 to
      0.7 mM). In solution, a complex between GDP-Fuc donor and the divalent cation
      Mn2+ was observed by electrospray ionization mass spectrometry, in a 1:1
      stoichiometry. These results indicated that Mn2+ bound the enzyme and increased
      its affinity for the acceptor; one possible functional role of manganese in
      catalysis could be as an electrophilic catalyst, co-ordinating the negative
      charges of the phosphate groups of the GDP-Fuc donor and promoting Fuc transfer.
      At low pH values such role would be played by the proton.

PMID- 14977361
TI  - Qualitative and quantitative composition of pigments in Phaeodactylum tricornutum
      (Bacillariophyceae) stressed by iron.
AB  - The effect of Fe(III) deficiency on qualitative and quantitative changes in
      pigment composition in Phaeodactylum tricornutum Bohlin was demonstrated by HPLC
      and AAS. Maximum content of pigments showed the diatom cells incubated at the
      optimum iron concentration, i.e., 10 microM. The contents of chlorophyll a,
      chlorophyll c1 + c2, fucoxanthin, diadinoxanthin and beta,beta-carotene were
      109.99, 20.16, 40.39, 1.29 and 1.48 fg per cell, respectively. The results
      obtained showed that Fe(III) affected qualitative and quantitative pigment
      composition in P. tricornutum. The content of individual pigments, proportions
      between accompanying pigments and their ratios to chlorophyll a were important
      indicators of phytoplankton response to iron stress. The strong reduction in
      beta,beta-carotene content, several times (2-5) increase in diadinoxanthin level
      as compared to beta,beta-carotene, and high amount of diadinoxanthin in relation
      to chlorophyll a were observed in algae growing at very low Fe(III)
      concentrations, 0.001 and 0.01 microM. The data suggested that phytoplankton
      pigments could be a potential physiological marker.

PMID- 14977362
TI  - Catecholates and mixed catecholate hydroxamates as artificial siderophores for
      mycobacteria.
AB  - Different mono-, bis- or triscatecholates and mixed mono- or biscatecholate
      hydroxamates were synthesized as potential siderophores for mycobacteria.
      SiderOphore activity was tested by growth promotion assays using wild type
      strains and iron transport mutants of mycobacteria as well as Gram-negative
      bacteria. Some triscatecholates and biscatecholate hydroxamates were active in
      mutants of Mycobacterium smegmatis deficient in mycobactin and exochelin
      biosynthesis or exochelin permease, respectively, indicating an uptake route
      independent of the exochelin/mycobactin pathway. Structure activity relationships
      were studied. Ampicillin conjugates of some of these compounds were inactive
      against mycobacteria but active against Gram-negative bacteria.

PMID- 14977363
TI  - Cadmium-induced apoptosis in C6 glioma cells: influence of oxidative stress.
AB  - Cadmium has recently been shown to induce apoptosis in C6 glioma cells via
      disruption of the mitochondrial membrane potential and subsequent caspase 9
      activation. Here we show that both H2O2 and CdCl2 induced apoptotic DNA
      fragmentation in C6 cells. The employment of glutathione as an antioxidant
      prevented the induction of apoptotic DNA fragmentation by cadmium completely and
      catalase strongly reduced cadmium-induced DNA fragmentation suggesting that
      cadmium exerts its apoptotic effects at least partly via the production of H2O2.
      Apoptosis may be induced by cadmium indirectly through formation of oxidative
      stress, e.g., by inhibition of antioxidant enzymes. After incubation of C6 cells
      with cadmium for short times (up to 4 h), we analyzed the formation of
      intracellular reactive oxygen species and cellular lipid peroxidation. After 1 h
      of incubation with inreasing concentrations of CdCl2 (1-500 microM), no increase
      in dichlorofluorescein fluorescence was found. At variance, lipid peroxidation
      was slightly elevated after 2 h incubation with cadmium (50-100 microM).
      Furthermore, we analyzed the modulation of markers for oxidative stress after
      prolonged (24 h) exposure to cadmium. The intracellular glutathione content as
      measured using the fluorescent probe monobromobimane was decreased after
      incubation with CdCl2 (0.5-10 microM) for 24 h. Furthermore, we measured the
      effect of cadmium on the level of oxidized DNA lesions (predominantly 8
      hydroxyguanine) using the bacterial Fpg-DNA-repair protein. After 24 h of
      incubation with 5 microM CdCl2 we found a sixfold increase in Fpg-sensitive DNA
      lesions. We conclude that short time incubations with cadmium (up to 4 h) caused
      only slight or insignificant effects on the generation of reactive oxygen species
      (formation of thiobarbituric acid reactive substances, fluorescence of
      dichlorofluorescein), whereas incubation with this heavy metal for 24 h lead to a
      decrease in intracellular glutathione concentration and an increase in oxidative
      DNA-lesions. Our data demonstrate that cadmium as similar to H2O2 is a potent
      inducer of apoptosis in C6 cells. Even if cadmium unlike Fenton-type metals can
      not produce reactive oxygen species directly, the apoptotic effects of cadmium at
      least in part are mediated via induction of oxidative stress. Because both
      apoptosis and oxidative stress are thought to play important roles in
      neurodegenerative diseases, low concentrations of cadmium that initiate
      programmed cell death may lead to a selective cell death in distinct brain
      regions via generation of oxidative stress.

PMID- 14977364
TI  - The respiratory inhibitor antimycin A specifically binds Fe(III) ions and
      mediates utilization of iron by the halotolerant alga Dunaliella salina
      (Chlorophyta).
AB  - It is demonstrated that Antimycin A (AA), a respiratory inhibitor produced by
      Streptomyces bacteria, forms lipophylic complexes with Fe(III) ions.
      Spectroscopic titration indicates that Fe(III) ions interact with 2AA molecules.
      At growth-limiting Fe concentrations, AA mediates Fe uptake and promotes growth
      and chlorophyll synthesis better than other Fe chelators in the halotolerant alga
      Dunaliella salina. It is proposed that AA enhances Fe bioavailability in
      hypersaline solutions by formation of lipophylic Fe-AA complexes which are taken
      up and utilized by the algae. The results suggest that the respiratory inhibitor
      AA can affect Fe metabolism in microorganisms.

PMID- 14977365
TI  - Studies on endocytic mechanisms of the Menkes copper-translocating P-type ATPase
      (ATP7A; MNK). Endocytosis of the Menkes protein.
AB  - The human X-linked recessive copper deficiency disorder, Menkes disease, is
      caused by mutations in the ATP7A (MNK) gene, which encodes a transmembrane copper
      transporting P-type ATPase (MNK). The MNK protein is localised to the Golgi
      apparatus and relocalises to the plasma membrane when copper levels are elevated.
      Previous studies have identified a C-terminal di-leucine endocytic motif
      (L1487L1488) in MNK, thought to direct it into the clathrin-mediated endocytic
      pathway. To determine whether MNK is internalised via clathrin-dependent
      endocytosis, this pathway was blocked in MNK-overexpressing HeLa cells by the
      transient expression of dominant negative dynamin and Eps15 mutants. MNK
      internalisation was not inhibited in such cells. MNK internalisation was
      inhibited in cells treated with hypertonic sucrose that not only blocked clathrin
      mediated endocytosis but also fluid-phase endocytosis. These studies, together
      with earlier studies on the requirement for L1487L1488, suggest that MNK can
      utilise both clathrin-dependent and clathrin-independent endocytosis in HeLa
      cells.

PMID- 14977366
TI  - Regulation of cannabinoid CB1 receptors in the central nervous system by chronic
      cannabinoids.
AB  - Marijuana produces a number of characteristic behaviors in humans and animals,
      including memory impairment, antinociception, and locomotor and psychoactive
      effects. However, tolerance and dependence to cannabinoids develops after chronic
      use, as demonstrated both clinically and in animal models. The potential
      therapeutic benefits of certain cannabinoid-mediated effects, as well as the use
      of marijuana for its psychoactive properties, has raised interest in
      understanding the cellular adaptations produced by chronic administration of this
      class of drugs. The primary active constituent of marijuana, delta9
      tetrahydrohydrocannabinol (THC), binds to specific G-protein-coupled receptors.
      The central nervous system (CNS) effects of THC are mediated by CB1 receptors,
      which couple primarily to inhibitory G-proteins. High levels of CB1 receptors are
      found in the basal ganglia, hippocampus, cortex, and cerebellum, consistent with
      the profile of behavioral effects. Studies over the past decade have determined
      that CB1 receptors undergo downregulation and desensitization following chronic
      administration of THC or synthetic cannabinoid agonists. In general, these
      adaptations are regionally widespread and of considerable magnitude, and are
      thought to contribute to tolerance to cannabinoid-mediated behavioral effects.
      Adaptation at the effector level has been more difficult to characterize,
      although it appears that alterations in cyclic adenosine monophosphate (cAMP) and
      protein kinase A (PKA) activity may be particularly important in cannabinoid
      dependence. A striking characteristic of CB 1 receptor adaptation is the region
      dependence of the magnitude and rate of development of downregulation and
      desensitization. These regional differences may provide interesting insights into
      the mechanisms of CB1 receptors receptor signaling in different brain regions.
      Moreover, region-specific adaptations in CB1 receptors following chronic
      cannabinoid administration may produce differential adaptations at the in vivo
      level.

PMID- 14977367
TI  - GABAergic cortical neuron chromatin as a putative target to treat schizophrenia
      vulnerability.
AB  - Inhibitory GABAergic interneurons of prefrontal cortex (PFC) appear to play an
      important role in the regulation of intermittent pyramidal neuron columnary
      firing and in the neuronal plasticity that mediate cognitive functions. In
      schizophrenia (SZ), cognitive defects and dysfunctions in pyramidal neuronal
      columnary firing appear to depend on abnormalities of GABAergic neurons. These
      abnormalities include a decrease of GAD67 and reelin expression, which result in
      a reduction of cortical inhibitory input to spine postsynaptic densities as a
      result of the decrease of GABA concentration at the synaptic cleft, and of
      neurotrophic stimuli as a result of the decrease of reelin secreted into the
      extracellular matrix. Our studies show that alterations in chromatin remodeling
      related to a selective upregulation of DNA-5-cytosine methyltransferase (DNMT)
      expression in GABAergic neurons of SZ PFC may induce a hypermethylation of reelin
      and GAD67 promoter CpG islands, which downregulates their expression. In
      addition, we report preliminary evidence suggesting that by targeting this
      chromatin-remodeling deficit with inhibitors of histone deacetylases (HDAC), it
      may be possible to reduce the DNMT upregulation via a covalent modification of
      nucleosomal histone tails, underscoring the possibility that by addressing a
      chromatin remodeling deficit, one may treat psychiatric disorders.

PMID- 14977368
TI  - Rodent models of depression: reexamining validity without anthropomorphic
      inference.
AB  - This review aims to stimulate new ways of thinking about how to model depression
      in rats and mice. The article is founded on the premise that anthropomorphic
      inferences should be removed entirely from research involving rodents. The
      application of animal models to study depression over the past 30 years has been
      based largely on nonempirical and hence nonscientific assumptions about
      psychological states that probably do not exist and certainly cannot be measured
      in rodents. Such assumptions may have led to the misinterpretation of some
      behaviors, such as decreased locomotor activity or decreased sucrose consumption,
      as symptoms of depression in rats. Previous research has also overemphasized the
      causal role of stress in depression. After reviewing major features of several
      commonly employed models, this article challenges traditional concepts about
      validity. Models are first evaluated based on the goals of the research.
      Screening for potential antidepressant compounds requires little or no
      consideration of the validity of the model. Issues of validity become more
      critical when attempting to study the neurobiological basis of depression. The
      primary importance of face validity is emphasized, and the value of various
      behavioral measures is assessed based on how directly they resemble discrete
      behavioral symptoms seen in depressed humans. A "neurobehaviorally mechanistic"
      approach is described. This approach relies on formulating discrete,
      neurobiological hypotheses to explain individual symptoms rather than to explain
      collections of symptoms or the entire disorder. The approach thus relies on
      pragmatic measures of operationally well-defined behavioral variables. The review
      concludes with the proposal that understanding the neurobiological basis for
      individual symptoms will ultimately yield a better understanding of depression.

PMID- 14977369
TI  - Rights and goods.

PMID- 14977370
TI  - Taking a stand against fraud and quackery in dentistry.

PMID- 14977371
TI  - The ethics of quackery and fraud in dentistry: a position paper.

PMID- 14977372
TI  - Quackery and fraud: understanding the ethical issues and responding.
AB  - A small number of dentists abuse their patients and the public trust in the
      profession by practicing quackery or fraudulent or questionable dentistry. Such
      practitioners can be classified as incompetent, as treating their patients as a
      means to personal fulfillment, as operating beyond their legal qualifications, or
      as being quacks, charlatans, or frauds. Ethical practice requires all five of
      these characteristics: informed consent, high benefit to risk ratio, competence,
      professional integrity, and reasoned scientific basis for care. Quacks and frauds
      place their own interests and judgment above those of their patients and the
      profession. Ethical dentists have obligations to act to protect their patients
      and the profession in their relationships with patients and with colleagues, as a
      profession in dealing with the public, and as a research community.

PMID- 14977373
TI  - The patient doesn't get it: a case.

PMID- 14977374
TI  - Our legacy: trust.

PMID- 14977375
TI  - There are several sides to the story.

PMID- 14977376
TI  - When the patient doesn't get it: "do the right thing".

PMID- 14977377
TI  - Betrayal of trust: reflections on questionable dental practices.
AB  - Dentistry is built on relationships of trust between individual practitioners and
      their patients and their colleagues. Increasing commercialism may be eroding some
      of that trust. An inventory of questionable practices is presented along with
      examples. These include inappropriate care that is unreasonable, aggressive, or
      intrusive; inappropriate billings, and misrepresentone's identity or
      qualifications. Although dentistry is predominantly provided by individual
      practitioners, it is not practiced in a vacuum.

PMID- 14977378
TI  - The role of professional journalism in protecting against questionable practice.
AB  - The editor in chief of the Journal of the Canadian Dental Association explains
      that professional journalism alone cannot be expected to protect against
      questionable practice but it plays a vital role in the network of resources that
      define standards of excellent and ethical care. According to some, the explosion
      of biomedical information has created a crisis as emerging science overwhelms
      practitioners' capacity to intelligently evaluate it and incorporate it into
      practice. Research in medicine shows that journals play only a part in decisions
      regarding practice patterns. Some initiatives taken by the Canadian Dental
      Association to publish professional literature relevant to practitioners' needs
      to remain current in order to prevent questionable dental practice are described.

PMID- 14977379
TI  - Quackery, fraud, and denturists.
AB  - Denturism is questionable dental practice, even in those few states where it is
      licensed. Incomplete or incompetent care is quackery. In the early 1980s a few
      states liberalized their laws to allow denturism to those who were educationally
      qualified. This experiment has generally failed because all accredited training
      programs have closed, because prices charged by denturists have about reached
      parity with dentists' fees, and because of limited demand for denturists'
      services. Because of the complexity of the message about scientifically-grounded
      oral health care and the populism of stories about the poor and underserved,
      dentists must be vigilant regarding their interactions with the media.

PMID- 14977380
TI  - Charlatans in dentistry: ethics of the NICO wars.
AB  - The scientific and diagnostic status of neuralgia-inducing cavitational
      osteonecrosis, NICO, has not been definitively established. A case is presented
      in favor of this diagnosis based on published literature. It is argued that the
      case against NICO has been made largely based on personal experiences, by
      innuendo, and through personal attacks rather than in scientific debate.

PMID- 14977381
TI  - Dental fraud: an introduction.
AB  - A manager of a dental benefits program defines fraud and abuse in the dental
      context. Such practices may cost as much as four billion dollars annually and
      have a damaging effect on the trust the profession places in the profession and
      on the way dentists relate to each other.

PMID- 14977382
TI  - The ethics of roles.
AB  - A distinction is made between ethical reasoning and moral behavior. Ethics
      courses in dental schools can aspire to improve the ability of students to
      reflect on ethical alternatives, but the most powerful influence for professional
      behavior comes from the role modeling of faculty members. The psycho-social,
      pedagogical, meta-ethical, and moral implications of faculty roles are examined.
      An example is given of how faculty assume this responsibility as they accept
      membership in the school community.

PMID- 14977383
TI  - The value of information.
AB  - The value of information is only indirectly a function of its objective
      characteristics. Of greater importance is its potential to add value to what its
      users can do. The dramatic recent reductions in the costs of distributing
      information have made protection against unwanted information more valuable than
      finding wanted information. This makes active information management a much
      prized skill. Suggestions are offered for reducing the costs of information
      search and for framing the search question at the correct level of specificity.

PMID- 14977384
TI  - Advanced glycation endproduct crosslinking in the cardiovascular system:
      potential therapeutic target for cardiovascular disease.
AB  - Advanced glycation endproducts (AGEs) are formed by a reaction between reducing
      sugars and biological amines. Because of their marked stability, glycated
      proteins accumulate slowly over a person's lifespan, and can contribute to age
      associated structural and physiological changes in the cardiovascular system such
      as increased vascular and myocardial stiffness, endothelial dysfunction, altered
      vascular injury responses and atherosclerotic plaque formation. The mechanisms by
      which AGEs affect the cardiovascular system include collagen crosslinking,
      alteration of low-density lipoprotein molecules and impairment of cellular nitric
      oxide signalling through their interaction with AGE receptors (RAGEs). Thus, the
      accumulation of AGEs may help to explain the increased cardiac risk associated
      with aging as well as diabetes mellitus and hypertension, two conditions that
      accelerate and enhance AGE formation. A variety of new pharmacological approaches
      are being developed to reduce the pathophysiological impact of AGEs. These agents
      can prevent AGE and AGE crosslink formation, break pre-existing AGE crosslinks,
      and block the interaction between AGEs and RAGEs. Such agents have been shown to
      reduce vascular and myocardial stiffness, inhibit atherosclerotic plaque
      formation and improve endothelial function in animal models. Improvement in
      vascular compliance has also been demonstrated with AGE crosslink breakers in
      clinical trials. These studies offer promise to reduce the cardiac risk
      associated with isolated systolic hypertension, diastolic dysfunction and
      diabetes.

PMID- 14977385
TI  - Treatment of HIV infection in pregnant women: antiretroviral management options.
AB  - Increasing rates of HIV infection in women worldwide, especially among those of
      childbearing age, reinforce the importance of understanding the management of HIV
      in pregnancy. Over the past decade, significant advances have been made in the
      prevention of vertical HIV transmission, including the use of single and
      combination antiretroviral therapy, elective caesarean section as the preferred
      mode of delivery and the elimination of breast feeding. Multiple clinical trials
      assessing antiretroviral therapy in pregnancy have been carried out worldwide.
      The first pivotal clinical trial, the AIDS Clinical Trials Group (ACTG) 076
      study, was conducted in 1994 using a three-part zidovudine regimen. Despite the
      success of this regimen at decreasing rates of vertical transmission, it is not
      affordable in many developing countries. Consequently, many international
      clinical trials have concentrated on short-course antiretroviral regimens
      including zidovudine alone, zidovudine and lamivudine, and nevirapine alone. In
      the developed world, the management of nonpregnant HIV-infected individuals has
      also undergone significant advances and has implications for the management of
      HIV in pregnancy. A number of countries have participated in the development of
      guidelines for the management of HIV in pregnancy, which recommend that HIV
      infected pregnant women should be offered combination antiretroviral therapy
      based on viral load and CD4+ cell count cut-offs used for individuals who are not
      pregnant, preferably with the inclusion of zidovudine. However, to maximise the
      benefits to their offspring, therapy is recommended at lower viral load
      thresholds than for nonpregnant adults. For antiretroviral-naive women, therapy
      is deferred until the second trimester because of the potential and uncertain
      risk of teratogenesis and the low risk of transmission during this period.
      Research has also found that maternal factors including viral load, immune
      status, chorioamnionitis, prematurely ruptured membranes and, to a lesser extent,
      intravenous drug use and smoking are associated with increased vertical
      transmission. These represent potentially modifiable risk factors that should be
      addressed before and throughout pregnancy. Despite the benefits of antiretroviral
      therapy to reduce HIV vertical transmission, its use can be complicated by known
      and unknown risks of toxicity to the mother, fetus or both as well as carrying
      the risk of developing drug-resistant virus. The latter can potentially
      compromise future treatment options for both the mother and child. Other
      important challenges include the use of antiretroviral drugs during pregnancy
      when the mother does not meet criteria for them for her own health, and balancing
      the relative risks and benefits of elective caesarean section at various degrees
      of viral load suppression. Clinicians managing HIV in pregnancy need to keep up
      to date with all the literature to provide optimal care, including counselling to
      allow mothers to balance the risks and benefits while deciding on treatment for
      both themselves and their children.

PMID- 14977386
TI  - Treatment of hepatitis C in solid organ transplantation.
AB  - Hepatitis C virus (HCV) infection is highly prevalent worldwide, and results in
      significant morbidity and mortality. HCV frequently infects haemodialysis
      patients and appears to impact on long-term survival of kidney transplant
      recipients. Therefore, treatment is recommended for kidney transplant candidates
      before transplantation and should be avoided following transplantation because of
      a high risk of allograft rejection. HCV infection does not appear to influence
      survival in cardiac transplant recipients and cardiac transplant recipients
      should also not be treated. In general, HCV-infected patients with cirrhosis are
      not considered as candidates for either kidney or cardiac transplantation given
      their risk of decompensation. HCV is the most common indication for liver
      transplantation and re-infection with varying degrees of liver injury is
      universal. Survival after liver transplantation is reduced among HCV-infected
      patients when compared with uninfected controls. Therefore, treatment using
      interferon and ribavirin is advocated; however, such therapy is frequently
      limited by adverse effects. Thus, improved antiviral treatment modalities are
      eagerly awaited in the transplant setting.

PMID- 14977387
TI  - Differentiating factors between erythropoiesis-stimulating agents: a guide to
      selection for anaemia of chronic kidney disease.
AB  - Endogenous erythropoietin (EPO) consists of a central polypeptide core covered by
      post-translationally linked carbohydrates. Three of the four currently available
      erythropoiesis stimulating agents (ESA)--epoetin-alpha, epoetin-beta and epoetin
      omega- are composed of an identical amino acid sequence, but glycosylation varies
      as a result of type- and host cell-specific differences in the production
      process. Epoetin-alpha and epoetin-beta resemble each other with respect to
      molecular characteristics and pharmacokinetic data, although epoetin-beta has a
      higher molecular weight, a lower number of sialylated glycan residues and
      possibly slight pharmacokinetic advantages such as a longer terminal elimination
      half-life. A serious adverse effect of long-term administration of ESA is pure
      red cell aplasia. This effect has been observed predominantly with subcutaneous
      use of epoetin-alpha produced outside the US after albumin was removed from the
      formulation. In comparison with the intravenous route, subcutaneous
      administration of epoetin has been reported to have a dose-sparing effect in some
      studies. Epoetin-beta has been the subject of studies aimed at proving efficacy
      with a reduced administration frequency but results are not unequivocal. Epoetin
      omega is produced in a different host cell than all other erythropoietic agents,
      hence glycosylation and pharmacokinetics are different. Small-scale clinical
      studies found epoetin-omega to be slightly more potent than epoetin-alpha.
      Epoetin-delta is a recently approved agent produced by human cells that are
      genetically engineered to transcribe and translate the EPO gene under the control
      of a newly introduced regulatory DNA sequence. However, epoetin-delta is not yet
      on the market and few data are available. The erythropoietin analogue darbepoetin
      alpha carries two additional glycosylation sites that permit a higher degree of
      glycosylation. Consequently, in comparison with the other epoetins, darbepoetin
      alpha has a longer serum half-life and a higher relative potency, which further
      increases with extension of the administration interval. Dosage requirements of
      darbepoetin-alpha do not appear to differ between the intravenous and
      subcutaneous routes of administration. The less frequent administration of
      darbepoetin-alpha in comparison to the other epoetins may reduce drug costs in
      the long term, but the variability in dosage or dosage frequency required within
      a single patient is high. Further studies should be aimed at defining predictors
      of the individual demand for erythropoietic agents, thereby allowing
      nephrologists to prescribe a cost-effective, individualised regimen.

PMID- 14977388
TI  - Ciclesonide.
AB  - Ciclesonide is an inhaled corticosteroid (delivered via a hydrofluoroalkane
      metered-dose inhaler) that is converted to an active metabolite, desisobutyryl
      ciclesonide, in the lung, thereby minimising effects on endogenous cortisol. In
      two 12-week, randomised studies in patients with asthma, ciclesonide 80 or 320
      microg once daily was at least as effective as budesonide 400 microg/day at
      increasing forced expiratory volume in 1 second (FEV1) and forced vital capacity
      (FVC) from baseline; ciclesonide 320 microg daily was significantly more
      effective than budesonide 400 microg once daily in one study. In a randomised,
      double-blind study in patients with asthma controlled with high-dosages of
      inhaled corticosteroids, FEV(1) and FVC decreased significantly from baseline at
      12 weeks in patients receiving ciclesonide 320 microg daily or budesonide 400
      microg daily; peak expiratory flow values decreased significantly only in
      patients receiving budesonide. Inhaled ciclesonide 80 or 320 microg daily
      improved asthma symptom scores and decreased the use of rescue medication by a
      similar, significant amount to budesonide 400 microg/day in two 12-week studies.
      Inhaled ciclesonide was generally well tolerated in patients with asthma.
      Ciclesonide did not suppress biochemical markers of adrenal function in 52-week
      studies. The long-term (>52 weeks) systemic effects of ciclesonide remain
      unknown.

PMID- 14977394
TI  - Some early history of membrane molecular biology.
AB  - This article is mostly about the beginnings of the molecular biology of
      membranes, covering the decade 1964-1974. It is difficult to read (or write) this
      article because of a sense of deja vu. Most of the material in it is considered
      commonplace today, having been established experimentally since then. But at the
      time this work was begun, practically nothing was known about the molecular
      structure and the mechanisms of the functions of membranes. This situation
      existed because no membrane proteins of the kind I called integral had as yet
      been isolated in a pure state, and therefore none had had their amino acid
      sequence determined. The first integral membrane protein to be so characterized
      was human erythrocyte glycophorin, in 1978. It was the use of the thermodynamic
      reasoning that had been developed for the study of water-soluble proteins,
      together with the information from several key experiments carried out in a
      number of laboratories during the early decade, that led us to the fluid mosaic
      model of membrane structure in 1972. Without direct evidence to confirm the model
      in 1971-1972, my colleagues and I nevertheless had the confidence in it to pursue
      some of the consequences of the model for a new understanding of many membrane
      functions, which I present here in some detail. Finally, I discuss two recent
      high-resolution X-ray crystallographic studies of integral proteins to ask how
      well the structural and functional proposals that we derived from the fluid
      mosaic model fit these remarkably detailed X-ray results.

PMID- 14977395
TI  - Myocardial aging and senescence: where have the stem cells gone?
AB  - Heart failure remains a leading cause of hospital admissions and mortality in the
      elderly, and current interventional approaches often fail to treat the underlying
      cause of pathogenesis. Preservation of structure and function in the aging
      myocardium is most likely to be successful via ongoing cellular repair and
      replacement, as well as survival of existing cardiomyocytes that generate
      contractile force. Research has led to a paradigm shift driven by application of
      stem cells to generate cardiovascular cell lineages. Early controversial findings
      of pluripotent precursors adopting cardiac phenotypes are now widely accepted,
      and current debate centers upon the efficiency of progenitor cell incorporation
      into the myocardium. Much work remains to be done in determining the relevant
      progenitor cell population and optimizing conditions for efficient
      differentiation and integration. Significant implications exist for treatment of
      pathologically damaged or aging myocardium since future interventional approaches
      will capitalize upon the use of cardiac stem cells as therapeutic reagents.

PMID- 14977396
TI  - Viral-based myocardial gene therapy approaches to alter cardiac function.
AB  - In recent years there has been a rapid expansion in our understanding of the
      molecular biology that underpins human physiology. In the heart, elegant
      molecular pathways have been elucidated, and derangements in these pathways have
      been identified as factors in cardiac disease. However, as our understanding has
      grown, we have recognized that there exist only relatively crude tools to effect
      changes in molecular pathophysiology. The ultimate promise of gene therapy is to
      correct the molecular derangements that cause illness. To bring this promise to
      fruition in the clinical arena, many problems need to be solved, and chief among
      these remains reliable and robust delivery of genes to the target organ. To this
      end, viral vectors have been utilized with success more frequently than any other
      method of gene delivery. The use of these vectors in the heart has already
      offered promising novel benefit for human ischemic heart disease, and studies in
      animal models have given glimpses of hope that gene therapy may provide future
      therapeutic benefit in heart failure by improving cardiac function.

PMID- 14977397
TI  - Developmental regulation of lung liquid transport.
AB  - The developing distal lung epithelium displays an evolving liquid transport
      phenotype, reflecting a changing and dynamic balance between Cl- ion secretion
      and Na+ ion absorption, which in turn reflects changing functional requirements.
      Thus in the fetus, Cl--driven liquid secretion predominates throughout gestation
      and generates a distending pressure to stretch the lung and stimulate growth.
      Increasing Na+ absorptive capacity develops toward term, anticipating the switch
      to an absorptive phenotype at birth and beyond. There is some empirical evidence
      of ligand-gated regulation of Cl- transport and of regulation via changes in the
      driving force for Cl- secretion. Epinephrine, O2, glucocorticoid, and thyroid
      hormones interact to stimulate Na+ absorption by increasing Na+ pump activity and
      apical Na+ conductance (GNa+) to bring about the switch from net secretion to net
      absorption as lung liquid is cleared from the lung at birth. Postnatally, the
      lung lumen contains a small Cl--based liquid secretion that generates a surface
      liquid layer, but the lung retains a large absorptive capacity to prevent
      alveolar flooding and clear edema fluid. This review explores the mechanisms
      underlying the functional development of the lung epithelium and draws upon
      evidence from classic integrative physiological studies combined with molecular
      physiology approaches.

PMID- 14977391
TI  - Cetirizine: a review of its use in allergic disorders.
AB  - Cetirizine is a selective, second-generation histamine H1 receptor antagonist,
      with a rapid onset, a long duration of activity and low potential for interaction
      with drugs metabolised by the hepatic cytochrome P450 system. Cetirizine was
      generally more effective than other H1 receptor antagonists at inhibiting
      histamine-induced wheal and flare responses. Cetirizine is an effective and well
      tolerated agent for the treatment of symptoms of seasonal allergic rhinitis
      (SAR), perennial allergic rhinitis (PAR) and chronic idiopathic urticaria (CIU)
      in adult, adolescent and paediatric patients. In adults with these allergic
      disorders, cetirizine was as effective as conventional dosages of ebastine (SAR,
      PAR, CIU), fexofenadine (SAR), loratadine (SAR, CIU) or mizolastine (SAR). This
      agent was significantly more effective, and with a more rapid onset of action,
      than loratadine in 2-day studies in environmental exposure units (SAR). In
      paediatric patients, cetirizine was as at least as effective as chlorphenamine
      (chlorpheniramine) [SAR], loratadine (SAR, PAR) and oxatomide (CIU) in the short
      term, and more effective than oxatomide and ketotifen (PAR) in the long term.
      Cetirizine was effective in reducing symptoms of allergic asthma in adults and
      reduced the relative risk of developing asthma in infants with atopic dermatitis
      sensitised to grass pollen or house dust mite allergens. It had a corticosteroid
      sparing effect in infants with severe atopic dermatitis and was effective in
      ameliorating reactions to mosquito bites in adults. Cetirizine was well tolerated
      in adults, adolescents and paediatric patients with allergic disorders. In adult,
      adolescent and paediatric patients aged 2-11 years, the incidence of somnolence
      with cetirizine was dose related and was generally similar to that with other
      second-generation H1 receptor antagonists. Although, its sedative effect was
      greater than that of fexofenadine in some clinical trials and that of loratadine
      or fexofenadine in a postmarketing surveillance study. In infants aged 6-24
      months, the tolerability profile of cetirizine was similar to that of placebo.
      Cetirizine did not have any adverse effects on cognitive function in adults, or
      cognitive function, behaviour or achievement of psychomotor milestones in
      paediatric patients. Cetirizine was not associated with cardiotoxicity.
      CONCLUSION: Cetirizine is well established in the treatment of symptoms of SAR,
      PAR or CIU. It demonstrated a corticosteroid-sparing effect and reduced the
      relative risk of developing asthma in sensitised infants with atopic dermatitis.
      Cetirizine was effective in the treatment of allergic cough and mosquito bites;
      however, its precise role in these indications has yet to be clearly established.
      On the basis of its favourable efficacy and tolerability profile and rapid onset
      of action, cetirizine provides an important option for the treatment of a wide
      range of allergic disorders.

PMID- 14977398
TI  - Mechanism of rectification in inward-rectifier K+ channels.
AB  - Inward rectifiers are a class of K+ channels that can conduct much larger inward
      currents at membrane voltages negative to the K+ equilibrium potential than
      outward currents at voltages positive to it, even when K+ concentrations on both
      sides of the membrane are made equal. This conduction property, called inward
      rectification, enables inward rectifiers to perform many important physiological
      tasks. Rectification is not an inherent property of the channel protein itself,
      but reflects strong voltage dependence of channel block by intracellular cations
      such as Mg2+ and polyamines. This voltage dependence results primarily from the
      movement of K+ ions across the transmembrane electric field along the pore, which
      is energetically coupled to the blocker binding and unbinding. This mutual
      displacement mechanism between several K+ ions and a blocker explains the
      signature feature of inward rectifier K+ channels, namely, that at a given
      concentration of intracellular K+, their macroscopic conductance depends on the
      difference between membrane voltage and the K+ equilibrium potential rather than
      on membrane voltage itself.

PMID- 14977399
TI  - Metabolic regulation of potassium channels.
AB  - Potassium (K+) channels exist in all three domains of organisms: eubacteria,
      archaebacteria, and eukaryotes. In higher animals, these membrane proteins
      participate in a multitude of critical physiological processes, including food
      and fluid intake, locomotion, stress response, and cognitive functions. Metabolic
      regulatory factors such as O2, CO2/pH, redox equivalents, glucose/ATP/ADP,
      hormones, eicosanoids, cell volume, and electrolytes regulate a diverse group of
      K+ channels to maintain homeostasis.

PMID- 14977400
TI  - Structure and function of glutamate receptor ion channels.
AB  - A vast number of proteins are involved in synaptic function. Many have been
      cloned and their functional role defined with varying degrees of success, but
      their number and complexity currently defy any molecular understanding of the
      physiology of synapses. A beacon of success in this medieval era of synaptic
      biology is an emerging understanding of the mechanisms underlying the activity of
      the neurotransmitter receptors for glutamate. Largely as a result of structural
      studies performed in the past three years we now have a mechanistic explanation
      for the activation of channel gating by agonists and partial agonists; the
      process of desensitization, and its block by allosteric modulators, is also
      mostly explained; and the basis of receptor subtype selectivity is emerging with
      clarity as more and more structures are solved. In the space of months we have
      gone from cartoons of postulated mechanisms to hard fact. It is anticipated that
      this level of understanding will emerge for other synaptic proteins in the coming
      decade.

PMID- 14977401
TI  - Biochemical indicators of stress and metabolism: applications for marine
      ecological studies.
AB  - Studies investigating the effects of temperature, food availability, or other
      physical factors on the physiology of marine animals have led to the development
      of biochemical indicators of growth rate, metabolic condition, and physiological
      stress. Measurements of metabolic enzyme activity and RNA/DNA have been
      especially valuable as indicators of condition in studies of marine invertebrates
      and fishes, groups for which accurate determination of field metabolic rates is
      difficult. Properly calibrated and applied, biochemical indicators have been
      successfully used in studies of rocky intertidal ecology, where two decades of
      experimentation have generated rigorous, testable models for determining the
      relative influences of biotic and abiotic factors on species distribution,
      abundance, and interaction. Biochemical indicators of condition and metabolic
      activity (metabolic enzymes, RNA/DNA) have been used to test nutrient
      productivity models by demonstrating tight linkages between nearshore
      oceanographic processes (such as upwelling) and benthic rocky intertidal
      ecosystems. Indices of condition and heat stress (heat shock proteins, or Hsps)
      have begun to be used to test environmental stress models by comparing condition,
      activity, and Hsp expression of key rocky intertidal predator and prey species.
      Using biochemical indicators of condition and stress in natural systems holds
      great promise for understanding mechanisms by which organisms respond to rapid
      environmental change.

PMID- 14977402
TI  - Field physiology: physiological insights from animals in nature.
AB  - Whereas comparative physiology documents the range of physiological variation
      across a range of organisms, field physiology provides insight into the actual
      mechanisms an organism employs to maintain homeostasis in its everyday life. This
      requires an understanding of an organism's natural history and is prerequisite to
      developing hypotheses about physiological mechanisms. This review focuses on a
      few areas of field physiology that exemplify how the underlying physiology could
      not have been understood without appropriate field measurements. The examples we
      have chosen highlight the methods and inference afforded by an application of
      this physiological analysis to organismal function in nature, often in extreme
      environments. The specific areas examined are diving physiology, the thermal
      physiology of large endothermic fishes, reproductive physiology of air breathing
      vertebrates, and endocrine physiology of reproductive homeostasis. These areas
      form a bridge from physiological ecology to evolutionary ecology. All our
      examples revolve around the central issue of physiological limits as they apply
      to organismal homeostasis. We view this theme as the cornerstone of physiological
      analysis and supply a number of paradigms on homeostasis that have been tested in
      the context of field physiology.

PMID- 14977403
TI  - Metabolic rate and body temperature reduction during hibernation and daily
      torpor.
AB  - Although it is well established that during periods of torpor heterothermic
      mammals and birds can reduce metabolic rates (MR) substantially, the mechanisms
      causing the reduction of MR remain a controversial subject. The comparative
      analysis provided here suggests that MR reduction depends on patterns of torpor
      used, the state of torpor, and body mass. Daily heterotherms, which are species
      that enter daily torpor exclusively, appear to rely mostly on the fall of body
      temperature (Tb) for MR reduction, perhaps with the exception of very small
      species and at high torpor Tb, where some metabolic inhibition may be used. In
      contrast, hibernators (species capable of prolonged torpor bouts) rely
      extensively on metabolic inhibition, in addition to Tb effects, to reduce MR to a
      fraction of that observed in daily heterotherms. In small hibernators, metabolic
      inhibition and the large fall of Tb are employed to maximize energy conservation,
      whereas in large hibernators, metabolic inhibition appears to be employed to
      facilitate MR and Tb reduction at torpor onset. Over the ambient temperature (Ta)
      range where torpid heterotherms are thermo-conforming, the Tb-Ta differential is
      more or less constant despite a decline of MR with Ta; however, in thermo
      regulating torpid individuals, the Tb-Ta differential is maintained by a
      proportional increase of MR as during normothermia, albeit at a lower Tb. Thermal
      conductance in most torpid thermo-regulating individuals is similar to that in
      normothermic individuals despite the substantially lower MR in the former.
      However, conductance is low when deeply torpid animals are thermo-conforming
      probably because of peripheral vasoconstriction.

PMID- 14977404
TI  - Sleep and circadian rhythms in mammalian torpor.
AB  - Sleep and circadian rhythms are the primary determinants of arousal state, and
      torpor is the most extreme state change that occurs in mammals. The view that
      torpor is an evolutionary extension of sleep is supported by electrophysiological
      studies. However, comparisons of factors that influence the expression of sleep
      and torpor uncover significant differences. Deep sleep immediately following
      torpor suggests that torpor is functionally a period of sleep deprivation. Recent
      studies that employ post-torpor sleep deprivation, however, show that the post
      torpor intense sleep is not homeostatically regulated, but might be a reflection
      of synaptic loss and replacement. The circadian system regulates sleep expression
      in euthermic mammals in such a way that would appear to preclude multiday bouts
      of torpor. Indeed, the circadian system is robust in animals that show shallow
      torpor, but its activity in hibernators is at least damped if not absent. There
      is good evidence from some species, however, that the circadian system plays
      important roles in the timing of bouts of torpor.

PMID- 14977405
TI  - Estrogens in the nervous system: mechanisms and nonreproductive functions.
AB  - The past decade has witnessed a growing interest in estrogens and their activity
      in the central nervous system, which was originally believed to be restricted to
      the control of reproduction. It is now well accepted that estrogens modulate the
      activity of all types of neural cells through a multiplicity of mechanisms.
      Estrogens, by binding to two cognate receptors ERalpha and ERbeta, may interact
      with selected promoters to initiate the synthesis of target proteins.
      Alternatively, the hormone receptor complex may interfere with intracellular
      signaling at both cytoplasmic and nuclear levels. The generation of cellular and
      animal models, combined with clinical and epidemiological studies, has allowed us
      to appreciate the neurotrophic and neuroprotective effects of estrogens. These
      findings are of major interest because estradiol might become an important
      therapeutic agent to maintain neural functions during aging and in selected
      neural diseases.

PMID- 14977406
TI  - The role of corepressors in transcriptional regulation by nuclear hormone
      receptors.
AB  - Nuclear receptors (also known as nuclear hormone receptors) are hormone-regulated
      transcription factors that control many important physiological and developmental
      processes in animals and humans. Defects in receptor function result in disease.
      The diverse biological roles of these receptors reflect their surprisingly
      versatile transcriptional properties, with many receptors possessing the ability
      to both repress and activate target gene expression. These bipolar
      transcriptional properties are mediated through the interactions of the receptors
      with two distinct classes of auxiliary proteins: corepressors and coactivators.
      This review focuses on how corepressors work together with nuclear receptors to
      repress gene transcription in the normal organism and on the aberrations in this
      process that lead to neoplasia and endocrine disorders. The actions of
      coactivators and the contributions of the same corepressors to the functions of
      nonreceptor transcription factors are also touched on.

PMID- 14977407
TI  - Molecular and integrative physiology of intestinal peptide transport.
AB  - Intestinal protein digestion generates a huge variety and quantity of short chain
      peptides that are absorbed into intestinal epithelial cells by the PEPT1
      transporter in the apical membrane of enterocytes. PEPT1 operates as an
      electrogenic proton/peptide symporter with the ability to transport essentially
      every possible di- and tripeptide. Transport is enantio-selective and involves a
      variable proton-to-substrate stoichiometry for uptake of neutral and mono- or
      polyvalently charged peptides. Neither free amino acids nor peptides containing
      four or more amino acids are accepted as substrates. The structural similarity of
      a variety of drugs with the basic structure of di- or tripeptides explains the
      transport of aminocephalosporins and aminopenicillins, selected angiotensin
      converting inhibitors, and amino acid-conjugated nucleoside-based antiviral
      agents by PEPT1. The high transport capacity of PEPT1 allows fast and efficient
      intestinal uptake of the drugs but also of amino acid nitrogen even in states of
      impaired mucosal functions. Transcriptional and post-transcriptional regulation
      of PEPT1 occurs in response to alterations in the nutritional status and in
      disease states, suggesting a prime role of this transporter in amino acid
      absorption.

PMID- 14977408
TI  - Oral rehydration therapy: new explanations for an old remedy.
AB  - Diarrheal diseases are among the most devastating illnesses globally, but the
      introduction of oral rehydration therapy has reduced mortality due to diarrhea
      from >5 million children, under the age of 5, in 1978 to 1.3 million in 2002.
      Variations of this simple therapy of salts and sugars are prevalent in
      traditional remedies in cultures world-wide, but only in the past four decades
      have the scientific bases for these remedies begun to be elucidated. This review
      aims to provide a broad understanding of the cellular basis of oral rehydration
      therapy. The features integral to the success of oral rehydration therapy are
      active glucose transport in the small intestine, commensal bacteria, and short
      chain fatty acid transport in the colon. The review examines these processes and
      their regulation and considers new approaches that might supplement oral
      rehydration therapy in controlling diarrheal diseases.

PMID- 14977409
TI  - Recent advances in carrier-mediated intestinal absorption of water-soluble
      vitamins.
AB  - Significant progress has been made in recent years toward understanding the
      mechanisms and regulation of intestinal absorption of water-soluble vitamins from
      the diet, especially those that are transported by a specialized carrier-mediated
      mechanism (i.e., ascorbic acid, biotin, folate, riboflavin, thiamin, and
      pyridoxine). The driving force involved in the uptake events and the molecular
      identity of the systems involved have been identified for a number of these
      vitamins. In addition, information about regulation of the uptake process of
      these micronutrients by intracellular and extracellular factors has been
      forthcoming. Furthermore, the 5' regulatory region of the genes that encode a
      number of these transporters has been characterized, thus providing information
      about transcriptional regulation of the transport events. Also of interest is the
      identification of existence of carrier-mediated mechanisms in human colonocytes
      that are capable of absorbing some of the vitamins that are synthesized by normal
      microflora of the large intestine. Although the contribution of the latter source
      of vitamins toward overall host nutrition is not clear and requires further
      investigations, it is highly likely that it does contribute toward the cellular
      homeostasis of these vitamins in the localized colonocytes.

PMID- 14977410
TI  - Learning mechanisms in addiction: synaptic plasticity in the ventral tegmental
      area as a result of exposure to drugs of abuse.
AB  - One of the central questions in neurobiology is how experience modifies neural
      function, and how changes in the nervous system permit an animal to adapt its
      behavior to a changing environment. Learning and adaptation to a host of
      different environmental stimuli exemplify processes we know must alter the
      nervous system because the behavioral output changes after experience.
      Alterations in behavior after exposure to addictive drugs are a striking example
      of chemical alterations of nervous system function producing long-lasting changes
      in behavior. The alterations produced in the central nervous system (CNS) by
      addictive drugs are of interest because of their relationship to human substance
      abuse but also because these CNS alterations produce dramatic, easily observed
      alterations in behavior in response to discrete stimuli. Considerable study has
      been given to behavioral and biochemical correlates of addiction over the past 50
      or more years; however, our understanding of the cellular physiological responses
      of affected CNS neurons is in its infancy. This review focuses on alterations in
      cellular and synaptic physiology in the ventral tegmental area (VTA) in response
      to addictive drugs.

PMID- 14977411
TI  - Localization of voltage-gated ion channels in mammalian brain.
AB  - The intrinsic electrical properties of neurons are shaped in large part by the
      action of voltage-gated ion channels. Molecular cloning studies have revealed a
      large family of ion channel genes, many of which are expressed in mammalian
      brain. Much recent effort has focused on determining the contribution of the
      protein products of these genes to neuronal function. This requires knowledge of
      the abundance and distribution of the constituent subunits of the channels in
      specific mammalian central neurons. Here we review progress made in recent
      studies aimed at localizing specific ion channel subunits using in situ
      hybridization and immunohistochemistry. We then discuss the implications of these
      results in terms of neuronal physiology and neuronal mechanisms underlying the
      observed patterns of expression.

PMID- 14977412
TI  - Myosin-1c, the hair cell's adaptation motor.
AB  - Given their prominent actin-rich subcellular specializations, it is no surprise
      that mechanosensitive hair cells of the inner ear exploit myosin molecules-the
      only known actin-dependent molecular motors-to carry out exotic but essential
      tasks. Recent experiments have confirmed that an unconventional myosin isozyme,
      myosin-1c, is a component of the hair cell's adaptation-motor complex. This
      complex carries out slow adaptation, provides tension to sensitize transduction
      channels, and may participate in assembly of the transduction apparatus. This
      review focuses on the detailed operation of the adaptation motor and the
      functional consequences of the incorporation of this specific myosin isozyme into
      the motor complex.

PMID- 14977413
TI  - Regulation of renal K transport by dietary K intake.
AB  - Extracellular K must be kept within a narrow concentration range for the normal
      function of neurons, skeletal muscle, and cardiac myocytes. Maintenance of normal
      plasma K is achieved by a dual mechanism that includes extrarenal factors such as
      insulin and beta-adrenergic agonists, which stimulate the movement of K from
      extracellular to intracellular fluid and modulate renal K excretion. Dietary K
      intake is an important factor for the regulation of K secretion: An increase in K
      intake stimulates secretion, whereas a decrease inhibits K secretion and enhances
      absorption. This effect of changes in dietary K intake on tubule K transport is
      mediated by aldosterone-dependent and -independent mechanisms. Recently, it has
      been demonstrated that the protein tyrosine kinase (PTK)-dependent signal
      transduction pathway is an important aldosterone-independent regulatory mechanism
      that mediates the effect of altered K intake on K secretion. A low-K intake
      stimulates PTK activity, which leads to increase in phosphorylation of cloned
      inwardly rectifying renal K (ROMK) channels, whereas a high-K intake has the
      opposite effect. Stimulation of tyrosine phosphorylation also suppresses K
      secretion in principal cell by facilitating the internalization of apical K
      channels in the collecting duct.

PMID- 14977414
TI  - The extracellular cyclic AMP-adenosine pathway in renal physiology.
AB  - Many cell types in the kidney express adenosine receptors, and adenosine has
      multiple effects on renal function. Although adenosine is produced within the
      kidney by several biochemical reactions, recent studies support a novel mechanism
      for renal adenosine production, the extracellular cAMP-adenosine pathway. This
      extracellular cAMP-adenosine pathway is initiated by efflux of cAMP from cells
      following activation of adenylyl cyclase. Extracellular cAMP is then converted to
      adenosine by the serial actions of ecto-phosphodiesterase and ecto-5'
      nucleotidase. When extracellular cAMP is converted to adenosine near the biophase
      of cAMP production and efflux, this local extracellular cAMP-adenosine pathway
      permits tight coupling of the site of adenosine production to the site of
      adenosine receptors. cAMP in renal compartments may also be formed by
      tissues/organs remote from the kidney. For example, stimulation of hepatic
      adenylyl cyclase by the pancreatic hormone glucagon increases circulating cAMP,
      which is filtered at the glomerulus and concentrated in the tubular lumen as
      water is extracted from the ultrafiltrate. Conversion of hepatic-derived cAMP to
      adenosine in the kidney completes a pancreatohepatorenal cAMP-adenosine pathway
      that may serve as an endocrine link between the pancreas, liver, and kidney.

PMID- 14977415
TI  - Alterations in SP-B and SP-C expression in neonatal lung disease.
AB  - The hydrophobic surfactant proteins, SP-B and SP-C, have important roles in
      surfactant function. The importance of these proteins in normal lung function is
      highlighted by the lung diseases associated with abnormalities in their
      expression. Mutations in the gene encoding SP-B result in severe, fatal neonatal
      lung disease, and mutations in the gene encoding SP-C are associated with chronic
      interstitial lung diseases in newborns, older children, and adults. This work
      reviews the current state of knowledge concerning the lung diseases associated
      with mutations in the SP-B and SP-C genes, and the potential roles of abnormal SP
      B and SP-C expression and genetic variation in these genes in other lung
      diseases.

PMID- 14977416
TI  - Epithelial-mesenchymal interactions in the developing lung.
AB  - Classical experiments in embryology have shown that normal growth, morphogenetic
      patterning, and cellular differentiation in the developing lung depend on
      interactive signaling between the endodermal epithelium and mesenchyme derived
      from splanchnic mesoderm. These interactions are mediated by a myriad of
      diffusible factors that are precisely regulated in their temporal and spatial
      expression. In this review we first describe factors regulating formation of the
      embryonic foregut. We then discuss the experiments demonstrating the importance
      of tissue interactions in lung patterning and differentiation. Finally, we detail
      the roles that a few key signaling systems-fibroblast growth factors and their
      receptors, sonic hedgehog and Gli genes, Wnt genes and beta-catenin, and BMP4
      play as mediators of epithelial-mesenchymal interactions in the developing lung.

PMID- 14977417
TI  - Genetically engineered mouse models for lung cancer.
AB  - The lung is a complex organ consisting of numerous cell types that function to
      ensure sufficient gas exchange to oxygenate the blood. In order to accomplish
      this function, the lung must be exposed to the external environment and at the
      same time maintain a homeostatic balance between its function in gas exchange and
      the maintenance of inflammatory balance. During the past two decades, as
      molecular methodologies have evolved with the sequencing of entire genomes, the
      use of in vivo models to elucidate the molecular mechanisms involved in pulmonary
      physiology and disease have increased. The mouse has emerged as a potent model to
      investigate pulmonary physiology due to the explosion in molecular methods that
      now allow for the developmental and tissue-specific regulation of gene
      transcription. Initial efforts to manipulate gene expression in the mouse genome
      resulted in the generation of transgenic mice characterized by the constitutive
      expression of a specific gene and knockout mice characterized by the ablation of
      a specific gene. The utility of these original mouse models was limited, in many
      cases, by phenotypes resulting in embryonic or neonatal lethality that prevented
      analysis of the impact of the genetic manipulation on pulmonary biology. Second
      generation transgenic mouse models employ multiple strategies that can either
      activate or silence gene expression thereby providing extensive temporal and
      spatial control of the experimental parameters of gene expression. These highly
      regulated mouse models are intended to serve as a foundation for further
      investigation of the molecular basis of human disease such as tumorigenesis. This
      review describes the principles, progress, and application of systems that are
      currently employed in the conditional regulation of gene expression in the
      investigation of lung cancer.

PMID- 14977418
TI  - Bacteriorhodopsin.
AB  - Fourier transform infrared and Raman spectroscopy, solid-state NMR, and X-ray
      crystallography have contributed detailed information about the structural
      changes in the proton transport cycle of the light-driven pump,
      bacteriorhodopsin. The results over the past few years add up to a step-by-step
      description of the configurational changes of the photoisomerized retinal, how
      these changes result in internal proton transfers and the release of a proton to
      the extracellular surface and uptake on the other side, as well as the
      conservation and transformation of excess free energy during the cycle.

PMID- 14977419
TI  - The cytochrome bc1 complex: function in the context of structure.
AB  - The bc1 complexes are intrinsic membrane proteins that catalyze the oxidation of
      ubihydroquinone and the reduction of cytochrome c in mitochondrial respiratory
      chains and bacterial photosynthetic and respiratory chains. The bc1 complex
      operates through a Q-cycle mechanism that couples electron transfer to generation
      of the proton gradient that drives ATP synthesis. Genetic defects leading to
      mutations in proteins of the respiratory chain, including the subunits of the bc1
      complex, result in mitochondrial myopathies, many of which are a direct result of
      dysfunction at catalytic sites. Some myopathies, especially those in the
      cytochrome b subunit, exacerbate free-radical damage by enhancing superoxide
      production at the ubihydroquinone oxidation site. This bypass reaction appears to
      be an unavoidable feature of the reaction mechanism. Cellular aging is largely
      attributable to damage to DNA and proteins from the reactive oxygen species
      arising from superoxide and is a major contributing factor in many diseases of
      old age. An understanding of the mechanism of the bc1 complex is therefore
      central to our understanding of the aging process. In addition, a wide range of
      inhibitors that mimic the quinone substrates are finding important applications
      in clinical therapy and agronomy. Recent structural studies have shown how many
      of these inhibitors bind, and have provided important clues to the mechanism of
      action and the basis of resistance through mutation. This paper reviews recent
      advances in our understanding of the mechanism of the bc1 complex and their
      relation to these physiologically important issues in the context of the
      structural information available.

PMID- 14977420
TI  - Interpreting the BOLD signal.
AB  - The development of functional magnetic resonance imaging (fMRI) has brought
      together a broad community of scientists interested in measuring the neural basis
      of the human mind. Because fMRI signals are an indirect measure of neural
      activity, interpreting these signals to make deductions about the nervous system
      requires some understanding of the signaling mechanisms. We describe our current
      understanding of the causal relationships between neural activity and the blood
      oxygen-level-dependent (BOLD) signal, and we review how these analyses have
      challenged some basic assumptions that have guided neuroscience. We conclude with
      a discussion of how to use the BOLD signal to make inferences about the neural
      signal.

PMID- 14977421
TI  - Live optical imaging of nervous system development.
AB  - Although development of the nervous system is inherently a process of dynamic
      change, until recently it has generally been investigated by inference from
      static images. However, advances in live optical imaging are now allowing direct
      observation of growth, synapse formation, and even incipient function in the
      developing nervous system, at length scales from molecules to cortical regions,
      and over timescales from milliseconds to months. In this review, we provide
      technical background and present examples of how these new methods, including
      confocal and two-photon microscopy, GFP-based markers, and functional indicators,
      are being applied to provide fresh insight into long-standing questions of neural
      development.

PMID- 14977422
TI  - Control of the size of the human muscle mass.
AB  - This review is divided into two parts, the first dealing with the cell and
      molecular biology of muscle in terms of growth and wasting and the second being
      an account of current knowledge of physiological mechanisms involved in the
      alteration of size of the human muscle mass. Wherever possible, attempts have
      been made to interrelate the information in each part and to provide the most
      likely explanation for phenomena that are currently only partially understood.
      The review should be of interest to cell and molecular biologists who know little
      of human muscle physiology and to physicians, physiotherapists, and
      kinesiologists who may be familiar with the gross behavior of human muscle but
      wish to understand more about the underlying mechanisms of change.

PMID- 14977423
TI  - Comparison of the microbicidal and muramidase activities of mouse lysozyme M and
      P.
AB  - Lysozyme is one of the most abundant antimicrobial proteins in the airspaces of
      the lung. Mice express two lysozyme genes, lysozyme M and P, but only the M
      enzyme is detected in abundance in lung tissues. Disruption of the lysozyme M
      locus significantly increased bacterial burden and mortality following
      intratracheal infection with a Gram-negative bacterium. Unexpectedly, significant
      lysozyme enzyme activity (muramidase activity) was detected in the airspaces of
      uninfected lysozyme M-/- mice, amounting to 25% of the activity in wild-type
      mice. Muramidase activity in lysozyme M-/- mice was associated with increased
      lysozyme P mRNA and protein in lung tissue and bronchoalveolar lavage fluid
      respectively. The muramidase activity of recombinant lysozyme P was less than
      that of recombinant M lysozyme. Recombinant P lysozyme was also less effective in
      killing selected Gram-negative bacteria, requiring higher concentrations than
      lysozyme M to achieve the same level of killing. The lower antimicrobial activity
      of P lysozyme, coupled with incomplete compensation by P lysozyme in lysozyme M-/
      mice, probably accounts for the increased susceptibility of null mice to
      infection. Recombinant lysozyme M and P were equally effective in killing
      selected Gram-positive organisms. This outcome suggests that disruption of both M
      and P loci would significantly increase susceptibility to airway infections,
      particularly those associated with colonization by Gram-positive organisms.

PMID- 14977424
TI  - Characterization of an ankyrin repeat-containing Shank2 isoform (Shank2E) in
      liver epithelial cells.
AB  - Shank proteins are a family of multidomain scaffolding proteins best known for
      their role in organizing the postsynaptic density region in neurons. Unlike
      Shank1 and Shank3, Shank2 [also known as Pro-SAP1 (proline-rich synapse
      associated protein 1), CortBP1 (cortactin binding protein 1) or Spank-3] has been
      described as a truncated family member without an N-terminal ankyrin repeat
      domain. The present study utilized bioinformatics to demonstrate the presence of
      exons encoding ankyrin repeats in the region preceding the previously described
      Shank2 gene. cDNA sequencing of mRNA from epithelial cells revealed a novel
      spliceoform of Shank2, termed Shank2E, that encodes a predicted 200 kDa protein
      with six N-terminal ankyrin repeats. Shank2 mRNA from epithelial tissues was
      larger than transcripts in brain. Likewise, the apparent mass of Shank2 protein
      was larger in epithelial tissues (230 kDa) when compared with brain (165/180
      kDa). Immunofluorescence and membrane fractionation found Shank2E concentrated at
      the apical membrane of liver epithelial cells. In cultured cholangiocytes, co
      immunoprecipitation and detergent solubility studies revealed Shank2E complexed
      with actin and co-distributed with actin in detergent-insoluble lipid rafts.
      These findings indicate epithelial cells express an ankyrin repeat-containing
      Shank2 isoform, termed Shank2E, that is poised to co-ordinate actin-dependent
      events at the apical membrane.

PMID- 14977425
TI  - d24-hour changes in circulating prolactin, follicle-stimulating hormone,
      luteinizing hormone and testosterone in male rats subjected to social isolation.
AB  - BACKGROUND: This work analyzes the effect of social isolation (a mild stressor)
      on the 24-h variation of pituitary-testicular function in young Wistar rats,
      assessed by measuring circulating levels of prolactin, FSH, LH and testosterone.
      METHODS: Animals were either individually caged or kept in groups (4-5 animals
      per cage) under a 12:12 h light-dark cycle (lights on at 0800 h) for 30 days
      starting on day 35 of life. Rats were killed at 4-h intervals during a 24-h
      cycle, beginning at 0900 h. RESULTS: Isolation brought about a decrease in
      prolactin, LH and testosterone secretion and an increase of FSH secretion. In
      isolated rats the 24-h secretory pattern of prolactin and testosterone became
      modified, i.e., the maximum in prolactin seen in control animals at the beginning
      of the activity span was no longer detected, whereas the maximum in circulating
      testosterone taking place at 1700 h in controls was phase-delayed to 2100 h in
      isolated rats. CONCLUSION: Social isolation affects the 24-h variation of
      pituitary-testicular function in young rats. Secretion of prolactin, LH and
      testosterone decreases, and secretion of FSH increases, in isolated rats. The
      maximum in prolactin seen in group-caged rats at the beginning of the activity
      span is not observed in isolated rats. The maximum in circulating testosterone
      taking place at the second part of the rest span in controls is phase-delayed to
      the light-dark transition in isolated rats.

PMID- 14977426
TI  - Genome characteristics of primary carcinomas, local recurrences, carcinomatoses,
      and liver metastases from colorectal cancer patients.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer
      related deaths in the Western world, and despite the fact that metastases are
      usually the ultimate cause of deaths, the knowledge of the genetics of advanced
      stages of this disease is limited. In order to identify potential genetic
      abnormalities underlying the development of local and distant metastases in CRC
      patients, we have, by comparative genomic hybridization, compared the DNA copy
      number profiles of 10 primary carcinomas, 14 local recurrences, 7 peritoneal
      carcinomatoses, and 42 liver metastases from 61 CRC patients. RESULTS: The median
      number of aberrations among the primary carcinomas, local recurrences,
      carcinomatoses, and liver metastases was 10, 6, 13, and 14, respectively. Several
      genetic imbalances, such as gains of 7, 8q, 13q, and 20, and losses of 4q, 8p,
      17p, and 18, were common in all groups. In contrast, gains of 5p and 12p were
      more common in the carcinomatoses than in other stages of the disease. With
      hierarchical cluster analysis, liver metastases could be divided into two main
      subgroups according to clusters of chromosome changes. CONCLUSIONS: Each stage of
      CRC progression is characterized by a particular genetic profile, and both
      carcinomatoses and liver metastases are more genetically complex than local
      recurrences and primary carcinomas. This is the first genome profiling of local
      recurrences and carcinomatoses, and gains of 5p and 12p seem to be particularly
      important for the spread of the CRC cells within the peritoneal cavity.

PMID- 14977427
TI  - Cascade impactors for the size characterization of aerosols from medical
      inhalers: their uses and limitations.
AB  - Cascade impactors, including the multi-stage liquid impinger, are by far the most
      widely encountered means for the in vitro determination of the particle size
      distribution of aerosols from medical inhalers, both in product development,
      batch release and in applications with add-on devices. This is because they
      directly measure aerodynamic size, which is the most relevant parameter to
      describe particle transport within the respiratory tract. At the same time, it is
      possible to quantify the mass of active pharmaceutical ingredient in different
      size ranges independent of other non-physiologically active components of the
      formulation. We begin by providing an overview of the operating principles of
      impactors and then highlight the various configurations and adaptations that have
      been adopted to characterize the various classes of inhaler. We continue by
      examining the limitations of the cascade impaction method, in particular looking
      at potential sources of measurement bias and discussing both appropriate and
      inappropriate uses of impactor-generated data. We also present a synopsis of
      current developments, including the Next Generation Pharmaceutical Impactor, and
      automation of cascade impactors for routine inhaler performance measurements.

PMID- 14977428
TI  - Lung deposition and respirable mass during wet nebulization.
AB  - For metered dose inhalers (MDIs), high-flow cascade impaction with a United
      States Pharmacopia (USP) throat provides a useful prediction of in vivo lung and
      oropharyngeal aerosol deposition. Particles expected to deposit in the lung are
      included in the "fine particle fraction" measured on the bench. Comparable in
      vitro standards are not available for nebulizers. The present study compared
      aerosol deposition in an in vitro model using low-flow cascade impaction with
      deposition in vivo in human subjects. A low-flow (1 Lmin), 10-stage cascade
      impactor measured aerodynamic distributions of aerosolized interferon-gamma (IFN
      gamma) from two nebulizers (Misty-Neb and AeroEclipse). (99m)Technetium
      diethylene triaminepenta-acetic acid ((99m)Tc-DTPA) was used as the radiolabel.
      Two bench conditions were specified: no breathing (standing cloud) and simulated
      ventilation with a piston pump (tidal volume 750 mL frequency 25 per minute and
      duty cycle 0.5). Mass median aerodynamic diameter (MMAD) for both nebulizers was
      affected by ventilation (Misty-Neb vs. AeroEclipse: 5.2 vs. 4.6 microm for
      standing cloud and 3.1 vs. 2.2 microm during ventilation). In three subjects,
      measured values of oropharyngeal deposition averaged 68.1 +/- 0.08% for Misty-Neb
      and 30.9 +/- 0.03% for AeroEclipse. In vivo deposition patterns compared to
      aerosol distributions from both nebulizers indicated that, for wet nebulization,
      penetration of aerosol beyond the upper airways (fine particle fraction) will
      occur only for aerosol particles below 2.5 microm. This assessment requires that
      the bench aerosol distribution be measured under conditions of clinical use
      (i.e., during tidal breathing).

PMID- 14977429
TI  - Effect of tubing deposition, breathing pattern, and temperature on aerosol mass
      distribution measured by cascade impactor.
AB  - Aerosols produced by nebulizers are often characterized on the bench using
      cascade impactors. We studied the effects of connecting tubing, breathing
      pattern, and temperature on mass-weighted aerodynamic particle size aerosol
      distributions (APSD) measured by cascade impaction. Our experimental setup
      consisted of a piston ventilator, low-flow (1.0 L/min) cascade impactor, two
      commercially available nebulizers that produced large and small particles, and
      two "T"-shaped tubes called "Tconnector(cascade)" and "Tconnector(nebulizer)"
      placed above the impactor and the nebulizer, respectively. Radiolabeled normal
      saline was nebulized using an airtank at 50 PSIG; APSD, mass balance, and
      Tconnector(cascade) deposition were measured with a gamma camera and radioisotope
      calibrator. Flow through the circuit was defined by the air tank (standing cloud,
      10 L/min) with or without a piston pump, which superimposed a sinusoidal flow on
      the flow from the air tank (tidal volume and frequency of breathing). Experiments
      were performed at room temperature and in a cooled environment. With increasing
      tidal volume and frequency, smaller particles entered the cascade impactor
      (decreasing MMAD; e.g., Misty-Neb, 4.2 +/- 0.9 microm at lowest ventilation and
      2.7 +/- 0.1 microm at highest, p = 0.042). These effects were reduced in
      magnitude for the nebulizer that produced smaller particles (AeroTech II, MMAD
      1.8 +/- 0.1 to 1.3 +/- 0.1 microm; p = 0.0044). Deposition on Tconnector(cascade)
      increased with ventilation but was independent of cascade impactor flow. Imaging
      of the Tconnector(cascade) revealed a pattern of deposition unaffected by cascade
      impactor flow. These measurements suggest that changes in MMAD with ventilation
      were not artifacts of tubing deposition in the Tconnector(cascade). At lower
      temperatures, APSD distributions were more polydisperse. Our data suggest that,
      during patient inhalation, changes in particle distribution occur that are
      related to conditions in the tubing and may reduce the diameters of particles
      entering the patient. This effect is more significant for nebulizers producing
      large particles. Changes in ambient temperature did not affect these
      observations.

PMID- 14977430
TI  - Aerosol therapy and the fighting toddler: is administration during sleep an
      alternative?
AB  - Insufficient cooperation during administration of aerosols by pressurized metered
      dose inhaler (pMDI)/spacers is a problem in nearly 50% of treated children
      younger than 2 years. For these children, administration during sleep might be
      more efficient. However, it is unknown how much aerosol reaches the lungs during
      sleep. The aim of this study was to determine in vitro the lung dose in young
      children from a pMDI/spacer during sleep and while being awake. Breathing
      patterns were recorded by a pneumotachograph in 18 children (age 11 +/- 5.1
      months) during sleep and wakefulness. Next, breathing patterns were replayed by a
      computer-controlled breathing simulator to which an anatomically correct nose
      throat model of a 9-month-old child was attached. One puff of budesonide (200
      microg) was administered to the model via a metal spacer. Aerosol was trapped in
      a filter placed between model and breathing simulator. The amount of budesonide
      on the filter (5 lung dose) was analyzed by HPLC. For each of the 36 breathing
      patterns, lung dose was measured in triplicate. The sleep breathing patterns had
      significantly lower respiratory rate and peak inspiratory flows, and smaller
      variability in respiratory rate, tidal volume, and peak inspiratory flows. Lung
      dose (mean +/- SD) was 6.5 +/- 3.2 and 11.3 +/- 3.9 microg (p = 0.004) for the
      wake and sleep breathing pattern, respectively. This infant model-study shows
      that the lung dose of budesonide by pMDI/spacer is significantly higher during
      sleep compared to inhalation during wake breathing. Administration of aerosols
      during sleep might, therefore, be an efficient alternative for uncooperative
      toddlers.

PMID- 14977431
TI  - Studies of the human oropharyngeal airspaces using magnetic resonance imaging. I.
      Validation of a three-dimensional MRI method for producing ex vivo virtual and
      physical casts of the oropharyngeal airways during inspiration.
AB  - The oropharyngeal region of the human airways has been scanned using 3D MRI and
      the data used to produce a model cast. The scanning method used a triggering
      device, which enabled data collection at the same pressure drop in each breathing
      cycle to produce clear images free of motion-related artefacts. A comparison
      between two differing MR acquisition strategies was made in a single subject,
      multi-session study. 3D FISP MR imaging was found to produce the most reliable
      data. Excluding the buccal cavity, where tongue position was critical, the
      reproducibility of measured airway volumes and cross sectional areas between
      sessions was demonstrated. Inter-session total airway volume (excluding the
      mouth) reproducibility was of the order of 5% and for minimum cross sectional
      areas at the epiglottis and vocal cords was 10%. The production of a physical
      cast from the images led to a 5% increase in airway volume compared with the
      anatomical images but with some loss of fine detail. The data demonstrated the
      robustness of an ex-vivo means of studying oropharyngeal dimensions and dynamics
      which may contribute to advancements in the understanding of aerosol delivery of
      therapeutic agents.

PMID- 14977432
TI  - Effect of excipients on the stability and aerosol performance of nebulized
      aviscumine.
AB  - Pulmonary delivery is an attractive alternative route to deliver protein drugs
      that are currently delivered by injection. Inhalation therapy via nebulizers is a
      well accepted way for pulmonary application of proteins considering the
      formulation difficulties of MDIs or DPIs. This research presents the effect of
      variable excipients on the stability and aerosol performance of freeze-dried
      aviscumine after reconstitution and nebulization. Aviscumine formulations
      containing 100 mmol/L Tris buffer, 0.1% (w/v) Polysorbate 80, 0.01% (w/v) Na(2)
      EDTA and 8% (w/v) Hydroxyethyl starch have been lyophilized and reconstituted
      with a buffered isotonic solution pH 8. The aviscumine activity was determined by
      a binding assay directly after reconstitution and after nebulization with a
      PariBoy air-jet nebulizer, a Multisonic and a Systam ultrasonic nebulizer. The
      stabilization of aviscumine by the addition of variable buffer salts to the
      reconstitution medium, such as 50, 100, and 200 mmol/L Tris buffer, 20 and 100
      mmol/L phosphate buffer, and 20 and 100 mmol/L Tricine buffer, was studied. About
      50% of aviscumine activity was lost after 20 min nebulization time without any
      additives. Nevertheless, higher buffer concentrations confer greater stability.
      About 70% of the aviscumine activity could be retained by the addition 0.03%
      octanoyl-N-methylglucamide and 100 mmol/L Tricine to the reconstitution medium.

PMID- 14977433
TI  - Regarding the development and practice of cascade impaction testing, including a
      mass balance failure investigation tree.

PMID- 14977434
TI  - Antiproliferative effect of resveratrol in human prostate carcinoma cells.
AB  - Resveratrol, a polyphenolic phytoalexin found in grapes, may have potential for
      the prevention and treatment of human cancer. We report here that resveratrol
      inhibits the growth of human prostate carcinoma DU145 cells and provide a
      molecular explanation of the effect. Resveratrol treatment in DU145 cells
      resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell
      death. The antiproliferative effect of resveratrol was associated with the
      inhibition of D-type cyclins and cyclin-dependent kinase (Cdk) 4 expression, and
      the induction of tumor suppressor p53 and Cdk inhibitor p21. Moreover, the kinase
      activities of cyclin E and Cdk2 were inhibited by resveratrol without alteration
      of their protein levels. Resveratrol treatment also up-regulated the Bax protein
      and mRNA expression in a dose-dependent manner; however, Bcl-2 and Bcl-xL levels
      were not significantly affected. These effects were found to correlate with an
      activation of caspase-3 and caspase-9. Taken together, our study suggests that
      resveratrol has a strong potential for development as an agent for the prevention
      of human prostate cancer.

PMID- 14977435
TI  - Leptin gene expression and serum leptin levels in zinc deficiency: implications
      for appetite regulation in rats.
AB  - Zinc deficiency in animals causes impaired growth and anorexia, and the
      mechanisms for these symptoms of zinc deficiency are not yet clear. We
      investigated whether circulating leptin levels and gene expression would be
      dysregulated under zinc deficiency and what would be the implications for
      appetite in rats. In study 1, 24 Sprague-Dawley rats were provided consecutively
      with three different dietary zinc intake levels: Zn-adequate (30 mg/kg of diet),
      Zn-depleted (1 mg/kg of diet), and Zn-replete (50 mg/kg of diet), for 1, 2, and 2
      weeks, respectively. At the end of each dietary period, one-third of the rats
      were killed. In study 2, rats were assigned to one of the four Zn diet groups: Zn
      adequate (30 mg/kg of diet), pair-fed (30 mg/kg of diet), Zn-deficient (1 mg/kg
      of diet), or Zn-sufficient (50 mg/kg of diet), and were fed for 4 weeks. Tissue
      Zn and serum leptin were measured, and leptin gene expression in adipose tissues
      (inguinal and abdominal) was determined by reverse transcription-polymerase chain
      reaction and northern blotting. Blood subfractions as plasma, red blood cells,
      and mononuclear cells and liver Zn level were decreased during the Zn-depletion
      period (P <.05). Serum leptin showed a tendency to increase during the Zn
      depletion period and decreased back to the level of the Zn-repletion period.
      Leptin mRNA levels in inguinal adipocytes also increased during the Zn-depletion
      (P <.05) and Zn-deficient periods, which is consistent with the change in serum
      leptin. However, the decrease in leptin mRNA in abdominal adipocytes was not
      consistent with the increase in inguinal leptin levels and the change in serum
      leptin. Increased leptin levels in linguinal adipocytes is consistent with the
      expected physiological change of a decrease in appetite under Zn deficiency.
      However, before coming to any firm conclusion, further studies on adipose tissue
      specific leptin expression, including the appetite-related neuropeptides, are
      necessary for clarifying the cause of lower appetite in zinc deficiency.

PMID- 14977436
TI  - Polyphenolics in grape seeds-biochemistry and functionality.
AB  - Grape seeds are waste products of the winery and grape juice industry. These
      seeds contain lipid, protein, carbohydrates, and 5-8% polyphenols depending on
      the variety. Polyphenols in grape seeds are mainly flavonoids, including gallic
      acid, the monomeric flavan-3-ols catechin, epicatechin, gallocatechin,
      epigallocatechin, and epicatechin 3-O-gallate, and procyanidin dimers, trimers,
      and more highly polymerized procyanidins. Grape seed extract is known as a
      powerful antioxidant that protects the body from premature aging, disease, and
      decay. Grape seeds contains mainly phenols such as proanthocyanidins (oligomeric
      proanthocyanidins). Scientific studies have shown that the antioxidant power of
      proanthocyanidins is 20 times greater than vitamin E and 50 times greater than
      vitamin C. Extensive research suggests that grape seed extract is beneficial in
      many areas of health because of its antioxidant effect to bond with collagen,
      promoting youthful skin, cell health, elasticity, and flexibility. Other studies
      have shown that proanthocyanidins help to protect the body from sun damage, to
      improve vision, to improve flexibility in joints, arteries, and body tissues such
      as the heart, and to improve blood circulation by strengthening capillaries,
      arteries, and veins. The most abundant phenolic compounds isolated from grape
      seed are catechins, epicatechin, procyanidin, and some dimers and trimers.

PMID- 14977437
TI  - Effects of flavonoid-rich beverages on prostacyclin synthesis in humans and human
      aortic endothelial cells: association with ex vivo platelet function.
AB  - Diets rich in flavonoids have been associated with reduced risk for
      cardiovascular disease. This may be due, in part, to flavonoid-induced
      alterations in eicosanoid synthesis. Our objective was to identify plant-derived
      beverages that alter synthesis of prostacyclin in cultured human aortic
      endothelial cells (HAEC), and to determine if these beverages could alter in vivo
      6-keto-prostaglandin F(1alpha) (a stable metabolite of prostacyclin) synthesis
      and platelet function. HAEC were treated with nine commonly consumed beverages to
      determine their effects on prostacyclin synthesis under acute and chronic
      treatment regimens. Orange, purple grape, and pomegranate juices and coffee (6-9
      mL/kg) were then provided to 28 fasted, healthy adult subjects (eight men and 20
      women) on five separate days. Plasma samples were collected immediately following
      juice consumption (baseline), and at 2 and 6 hours post-consumption. On an acute
      basis, administration of HAEC with pomegranate juice increased media
      prostacyclin. Chronic exposure to purple grape and pomegranate juice increased
      aortic endothelial cell prostacyclin synthesis (38% and 61%, respectively; P
      <.05). The consumption of purple grape, pomegranate, and orange juice prolonged
      epinephrine/collagen-induced clotting time (P <.05). Purple grape juice increased
      plasma 6-keto-prostaglandin F(1alpha) (20%; P <.05) at 2 hours; pomegranate and
      orange juice did not significantly influence plasma prostacyclin concentrations.
      Consistent with the in vitro data, coffee consumption did not influence clotting
      time or plasma prostacyclin concentrations. These results indicate that the HAEC
      model system can provide a qualitative means to screen food and food-derived
      products for biologic activity related to cardiovascular health.

PMID- 14977438
TI  - Isoflavone supplements do not affect thyroid function in iodine-replete
      postmenopausal women.
AB  - Despite the safety review conducted by the U.S. Food and Drug Administration in
      the process of awarding a health claim for the cholesterol-lowering properties of
      soy protein, concerns about the possible goitrogenic effects of soybean
      isoflavones persist. Concerns are based primarily on in vitro research, animal
      studies, and older reports of goiter in infants fed soy formula not fortified
      with iodine. In a randomized, double blind, placebo-controlled study, we
      investigated the effect on thyroid function of a daily supplement containing 90
      mg (aglycone weight) of total isoflavones/day versus placebo in 38 postmenopausal
      women, 64-83 years old, not on hormone replacement therapy. Serum thyroid
      stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) were
      measured at baseline and after 90 and 180 days. In the supplement group, at
      baseline and 6 months, TSH (micro U/ml), T4 (nM), and T3 (nM) levels (mean +/-
      SE) were 3.00 +/- 0.44, 149.00 +/- 5.04, and 1.53 +/- 0.13, respectively, and
      3.49 +/- 0.52, 154.52 +/- 2.09, and 1.78 +/- 0.12, respectively. In the control
      group, levels at baseline and at 6 months were 3.35 +/- 0.51, 145.39 +/- 6.69,
      and 1.55 +/- 0.18, respectively, and 3.63 +/- 0.57, 153.77 +/- 6.64, and 1.75 +/-
      0.10, respectively. Intragroup differences for all three measures were
      statistically indistinguishable at 6 months, and levels were similar between the
      isoflavone supplement and placebo groups at each measurement. These results
      indicate that in this group of healthy iodine-replete subjects, soy isoflavones
      do not adversely affect thyroid function.

PMID- 14977439
TI  - In vitro anti-cancer activities in Caco-2 and HCT-116 cells of recombinant
      cystatin C prepared by a Pichia expression system.
AB  - Caco-2 and HCT-116 cells were used to access growth-inhibition and anti-invasion
      activity of recombinant cystatin C expressed in Pichia pastoris X33, G12W/H86V.
      The mutant G12W/H86V prepared by a pilot plant production system showed more than
      10% growth inhibition of Caco-2 cells at 0.56-56 nM concentrations. Growth
      inhibited cells had lower cathepsin L activity than the control cells that were
      not treated with the inhibitor. Conversely, the cathepsin B activity was not
      changed by treatment with G12W/H86V. The in vitro anti-invasion test using HCT
      116 cells showed that G12W/H86V suppressed the cell invasion by 15%, while its
      wild-type cystatin, aspartic protease inhibitor pepstatin A, and matrix
      metalloproteinase (MMP) inhibitor MMP-2/MMP-9 inhibitor III did not suppress cell
      invasion. These results indicate that the recombinant cystatin C with higher
      protease inhibitory activity effectively retards the growth and invasiveness of
      human colon carcinoma cells.

PMID- 14977440
TI  - Effects of ginger (Zingiber officinale Rosc.) on decreasing the production of
      inflammatory mediators in sow osteoarthrotic cartilage explants.
AB  - The herbal remedy Zingiber officinale (ginger root) has been used for perhaps
      thousands of years in the Far East to treat inflammatory diseases, including
      osteoarthritis. However, the anti-arthritic effect of ginger root has never been
      evaluated on osteoarthrotic cartilage of sow. The objective of this study was to
      investigate the effects of ginger root extract (GRE) on the viability and the
      production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) by sow
      osteoarthrotic cartilage explants. The cartilage explants (~20 mg/96-well plate)
      were grown in Ham's F-12/Dulbecco's Modified Eagle's Medium supplemented with 10%
      fetal bovine serum and antibiotics for 72 hours and depleted for 24 hours. GRE
      was then added at different concentrations (0-2,000 microg/mL), and the explants
      were allowed to grow for 24 hours. The cell viability was reduced (P<.05) with
      GRE >/=500 microg/mL, whereas it was not affected with GRE <100 microg/mL. In a
      follow-up experiment, the supernatants of cartilage explants with GRE (0-500
      microg/mL) in the presence of interleukin-1beta (2 ng/mL), tumor necrosis factor
      alpha (1 ng/mL), and lipopolysaccharides (10 microg/mL) were used to measure NO
      and PGE production. Increasing GRE concentration (1-100 microg/mL) reduced (P
      <.05) NO production by cartilage tissue explants, and a similar pattern was
      observed in the production of PGE(2). The inhibitory effects of GRE on NO and
      PGE(2) production by sow osteoarthrotic cartilage explants observed in this study
      suggest an important role for GRE as an anti-arthritic agent in osteoarthrosis in
      the sow.

PMID- 14977441
TI  - Effects of manufactured soluble dietary fiber from Quercus mongolica on hepatic
      HMG-CoA reductase and lipoprotein lipase activities in epididymal adipose tissue
      of rats fed high cholesterol diets.
AB  - This study investigated the effect of a manufactured soluble dietary fiber on
      lipid metabolism in rats fed high cholesterol diets. Soluble dietary fiber was
      prepared from wood chips of oak (Quercus mongolica). Male Sprague-Dawley rats
      weighing 100 +/- 10 g were randomly assigned to either a normal diet or five high
      cholesterol diets containing 1% cholesterol and different fiber supplements. The
      high cholesterol groups were subdivided into fiber-free diet (FF), 5% pectin
      (5P), 10% pectin (10P), 5% manufactured soluble dietary fiber (5QM), and 10%
      manufactured soluble dietary fiber (10QM) groups. Total serum cholesterol
      concentrations in all soluble dietary fiber-supplemented groups were lower than
      in the FF group. The high-density lipoprotein-cholesterol concentration in the FF
      group was significantly lower, compared with the normal group, but was increased
      in groups supplemented with soluble dietary fiber. Low-density lipoprotein
      cholesterol levels and the atherogenic index had the same tendency as total
      cholesterol concentration. Compared with the FF group, in the 5P, 5QM, 10P, and
      10QM groups hepatic triglyceride concentrations were 12%, 16%, 20%, and 24%
      lower, respectively, and hepatic cholesterol concentrations were 48%, 52%, 52%,
      and 58% lower, respectively. Hepatic 3-hydroxy-3-methylglutaryl-CoA reductase
      activity in the soluble fiber groups was significantly higher than in the FF
      groups, but lower than the normal group. When hepatic tissue was observed under a
      light microscope, the FF group had completely formed lipomas in the hepatic
      tissue, which led to fat deposits and then a fatty liver. The size and number of
      lipomas were lower in the soluble dietary fiber-fed groups, as compared with the
      group not fed dietary fiber. In conclusion, improvements in lipid metabolism were
      observed as a result of the manufactured soluble dietary fiber from the oak
      chips, and were similar to that seen for pectin. The preparation method for the
      soluble dietary fiber from oak chips successfully produced a functional soluble
      fiber.

PMID- 14977442
TI  - Genistein may prevent cadmium-induced bone loss in ovariectomized rats.
AB  - This study compared the ability of genistein, a soy isoflavone, with that of 17
      beta-estradiol to prevent bone loss in cadmium (Cd)-exposed ovariectomized (OVX)
      rats during growth. Female Wistar rats (4 weeks old) were either sham-operated
      (SH; n = 9/group) or OVX and placed on experimental diets (n = 9/group): OVX; OVX
      rats fed 50 ppm of CdCl(2) (OVX-Cd); OVX fed 50 ppm of CdCl(2) and 10 microg/kg
      of body weight genistein (OVX-Cd-G); and OVX fed 50 ppm of CdCl(2) and 10
      microg/kg of body weight estrogen (OVX-Cd-E). All rats were given free access to
      AIN-76 modified diet and drinking water, with or without Cd, for 8 weeks. The OVX
      groups gained more body weight than the SH group. Femoral weight was increased by
      feeding genistein and estradiol, whereas femoral length among groups was not
      significantly different. Femoral Cd content was significantly higher in the OVX
      Cd group than in the other groups. Both serum osteocalcin and calcium (Ca)
      concentrations, as well as urinary Ca, were significantly higher in the OVX-Cd
      group than in the other groups. Urinary excretion of Cd was significantly
      increased in Cd-OVX-G rats, and fecal Cd excretion was increased by feeding both
      genistein and estradiol. Femoral histomorpological changes in proliferative
      cartilage and hypertrophic cells in the OVX-Cd group showed that both cell types
      were decreased by feeding Cd, and irregular arrangements were observed in
      proliferative cells. However, both cells types exhibited normal distribution in
      OVX-Cd-G and OVX-Cd-E groups. These findings suggest that Cd/OVXinduced
      osteopenia or osteoporosis probably results from an increase in bone turnover.
      Genistein may be involved in stimulating Cd excretion and inhibiting Ca excretion
      from bone.

PMID- 14977443
TI  - Octacosanol supplementation increases running endurance time and improves
      biochemical parameters after exhaustion in trained rats.
AB  - This study evaluated the effects of octacosanol on running performance and
      related biochemical parameters in exercise-trained rats run to exhaustion on a
      treadmill. Male Sprague-Dawley rats were randomly assigned to one of three groups
      - sedentary control group (SC), exercise-trained control group (EC), and exercise
      trained, octacosanol-supplemented group (EO) - and raised on either control or
      octacosanol (0.75%)-supplemented diet with (or without for SC rats) exercise
      training for 4 weeks. EC rats ran 184% longer until exhaustion than SC rats (P
      <.01), while octacosanol-supplemented trained rats ran 46% longer than EC rats (P
      <.05). Under the exhausted state immediately following the running performance
      test, EO rats exhibited significantly higher plasma ammonia and lactate
      concentrations compared with the values for EC rats (P <.05). Although EO rats
      ran significantly longer until exhausted, their plasma glucose level and
      gastronecmius muscle glycogen concentration were not significantly different from
      those of EC rats. Dietary supplementation of octacosanol resulted in
      significantly higher creatine phosphokinase activity in plasma (44% increase, P
      <.01) and citrate synthase activity in muscle (16% increase, P<.01) of exercise
      trained rats. These results suggest that the ergogenic properties of octacosanol
      include the sparing of muscle glycogen stores and increases in the oxidative
      capacity in the muscle of exercise-trained rats.

PMID- 14977444
TI  - Ixeris dentata extract maintains glutathione concentrations in mouse brain tissue
      under oxidative stress induced by kainic acid.
AB  - The neuroprotective effects of a water fraction from the methanol extract of
      Ixeris dentata (WFID) against oxidative stress in the brain of mice challenged
      with kainic acid were examined by evaluating behavioral characteristics and
      biochemical parameters of oxidative stress. Male ICR mice were divided into three
      groups: a control group that received no treatment and two groups challenged with
      kainic acid either with or without WFID (1.0 g/kg) for 4 consecutive days. On day
      3 kainic acid (50 mg/kg) was intraperitoneally administered in the two challenged
      groups. When compared with the vehicle-treated control, no significant changes in
      body and brain weights were observed in mice administered WFID. Administration of
      kainic acid only caused a lethality of approximately 62.5%, and resulted in a
      significant decrease of total glutathione concentrations in the brain tissue.
      When WFID was investigated for neuroprotective action, WFID reduced the lethality
      (37.5%) of kainic acid, and the behavioral signs of its neurotoxicity. Moreover,
      the administration of WFID restored the glutathione concentrations in the
      cytosolic fraction of brain homogenate to control levels (P <.05). Furthermore,
      glutathione peroxidase activity was restored significantly (Plt;.05) in the
      cytosolic portion of brain homogenate, whereas glutathione reductase activity was
      not. These results suggest that I. dentata contains a functional agent that
      protects against oxidative stress in the brains of mice.

PMID- 14977445
TI  - Identification of nitric oxide metabolites in various honeys: effects of
      intravenous honey on plasma and urinary nitric oxide metabolites concentrations.
AB  - Honey has antibacterial activity, promotes healing, and enhances immunity. Its
      acidity, osmotic effects of its high content of sugar, and hydrogen peroxide are
      assumed to be responsible for its effects. In this study, various honeys were
      investigated for the presence of nitrite/nitrate, the stable nitric oxide (NO)
      metabolites, and the effects of intravenous infusion of honey on urinary and
      plasma NO end products were studied in healthy sheep. Seven kinds of honey,
      different in their origin (three from Yemen, two from the United Arab Emirates,
      one from Germany, and one from India), color, and duration of storage, were
      investigated for the presence of NO metabolites. The assessment of NO metabolites
      was performed before and after exposure of the honey samples to heating (80
      degrees C for 1 hour) or ultraviolet light (for 24 hours). Seven healthy male
      sheep were used for the study. Fresh unprocessed yellow honey (2 g/kg of body
      weight) was infused over a period of 45 minutes to each fasting sheep. Plasma and
      urinary NO metabolites were measured before and after the infusion. All the honey
      samples examined had various concentrations of NO metabolites; the highest
      concentration was in the fresh dark honey collected from Yemen, and the lowest in
      1-year-stored dark honey collected from India. Darker or fresh honeys contained
      more NO metabolites than light or stored honey. After heating, NO metabolites
      decreased in all the kinds of honey. After ultraviolet exposure, NO metabolites
      were decreased in four kinds of honey, increased in one kind, and unchanged in
      two kinds. The darker stored honey had more resistance to heating and ultraviolet
      exposure. Intravenous infusion of honey elevated urinary NO metabolites from 8.4
      +/- 7.4 micromol/L to 14.9 +/- 10 micromol/L during the first 60-90 min after
      infusion and to 35.2 +/- 34 micromol/L during the next 150-180 min. Plasma NO
      metabolites were increased during 1, 2, and 3 hours after infusion by 3%, 3.6%,
      and 17%, respectively. No side effects were reported with the use of intravenous
      honey. It might be concluded that honey contains various concentrations of NO
      metabolites. Its intravenous infusion increased plasma and urinary NO
      metabolites. It is assumed that NO might be responsible, in part, for the
      biological and therapeutic effects of honey.

PMID- 14977446
TI  - Inhibitory effect of some flavonoids on tumor necrosis factor-alpha production in
      lipopolysaccharide-stimulated mouse macrophage cell line J774.1.
AB  - Certain naturally occurring flavonoids affect immunoregulatory activities in
      vitro and in vivo against cytokine production. Since tumor necrosis factor (TNF)
      alpha is one of the major inflammatory cytokines, the effects of various dietary
      flavonoids on TNF-alpha production in lipopolysaccharide (LPS)-stimulated J774.1
      cells were evaluated in vitro. Flavones, flavonols, and chalcone are the most
      potent inhibitors of production of TNF-alpha. Flavanone, naringenin,
      anthocyanidin, pelargodinin, and cyanidin exhibit moderate inhibitory activity.
      In contrast, genistein isoflavone displays weak inhibition, while eriodictyol
      flavanone is inactive. It is clear that the double bond between carbons 2 and 3
      and the ketone group at position 4 of flavonoids are necessary for potent
      inhibitory effect. The difference in inhibitory action appears to depend on the
      categorized subclass of flavonoids.

PMID- 14977447
TI  - Effect of Maitake (Grifola frondosa) D-Fraction on the activation of NK cells in
      cancer patients.
AB  - Maitake D-Fraction, extracted from maitake mushroom, has been reported to exert
      its antitumor effect in tumor-bearing mice by enhancing the immune system through
      activation of macrophages, T cells, and natural killer (NK) cells. In a previous
      study, the combination of immunotherapy with the maitake D-Fraction and
      chemotherapy suggested that the D-Fraction may have the potential to decrease the
      size of lung, liver, and breast tumors in cancer patients. In the present study,
      we administered maitake D-Fraction to cancer patients without anticancer drugs,
      and at the same time NK cell activity was monitored to investigate whether the
      activity is closely related with disease progression. The numbers of CD4(+) and
      CD8(+) cells in the peripheral blood were measured in 10 patients, and NK cell
      activity was assessed using K-562 cells as target cells. Serum soluble
      interleukin-2 receptor (sIL-2R) levels in three patients and the expression of
      tumor markers in four patients were determined by enzyme-linked immunosorbent
      assay. The slight changes observed in the CD4(+) and CD8(+) cell numbers were
      independent of disease severity or stage as well as serum sIL-2R levels. In
      contrast, maitake D-Fraction hindered metastatic progress, lessened the
      expression of tumor markers, and increased NK cell activity in all patients
      examined. Thus maitake D-Fraction appears to repress cancer progression and
      primarily exerts its effect through stimulation of NK activity. In addition, we
      conclude that measurement of NK cell activity may be a useful clinical parameter
      in monitoring disease progression during and following immunotherapy with maitake
      D-Fraction.

PMID- 14977448
TI  - Modulatory effect of Scoparia dulcis in oxidative stress-induced lipid
      peroxidation in streptozotocin diabetic rats.
AB  - In light of evidence that diabetes mellitus is associated with oxidative stress
      and altered antioxidant status, we investigated the effect of Scoparia dulcis
      plant extracts (SPEt) (aqueous, ethanolic, and chloroform) in streptozotocin
      diabetic rats. Significant increases in the activities of insulin, superoxide
      dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, reduced
      glutathione, vitamin C, and vitamin E were observed in liver, kidney, and brain
      on treatment with SPEt. In addition, the treated groups also showed significant
      decreases in blood glucose, thiobarbituric acid-reactive substances, and
      hydroperoxide formation in tissues, suggesting its role in protection against
      lipid peroxidation-induced membrane damage. Thus, the results of the present
      study indicate that extracts of S. dulcis, especially the aqueous extract, showed
      a modulatory effect by attenuating the above lipid peroxidation in streptozotocin
      diabetes.

PMID- 14977449
TI  - Effects of chrysin on urinary testosterone levels in human males.
AB  - The equilibrium of sexual hormones in both sexes is controlled in vertebrates by
      the enzyme aromatase, a member of the cytochrome P450 superfamily, which
      catalyzes the conversion of androstenedione and testosterone into estrone and
      estradiol, respectively. Flavonoids are diphenolic compounds present in whole
      grains, legumes, fruits, and vegetables that are strongly implicated as
      protective in coronary heart disease, stroke, and cancer. One flavonoid, chrysin,
      found in high concentrations in honey and propolis, has been shown to be an
      inhibitor of aromatase enzyme activity. These foods are often used as
      supplements, particulary by sportsmen for their energetic and antioxidant
      properties. The aim of this study was to verify if daily treatment for 21 days
      with propolis and honey, containing chrysin, would modify urinary concentrations
      of testosterone in volunteer male subjects. In fact, aromatase inhibition by
      chrysin could block the conversion of androgens into estrogens with a consequent
      increase of testosterone, eventually measurable in urine samples. The obtained
      data did not show alterations of the levels of testosterone in the volunteers
      after 7, 14, and 21 days of treatment in comparison with baseline values and
      compared with measurements on the control subjects at the same time. In
      conclusion, the use of these foods for 21 days at the doses usually taken as oral
      supplementation does not have effects on the equilibrium of testosterone in human
      males.

PMID- 14977450
TI  - Antidepressant activity of quercetin, a bioflavonoid, in streptozotocin-induced
      diabetic mice.
AB  - Depression is highly prevalent in diabetics and is associated with poor glucose
      regulation and increased risk of diabetic complications. Identification and
      effective treatment of comorbid depression are increasingly being considered
      essential components of clinical care of diabetics. In the present study, the
      antidepressant activity of quercetin (50 and 100 mg/kg, i.p.), a bioflavonoid,
      was evaluated using the Porsolt forced swimming-induced behavioral despair test
      in control and 6-week-streptozotocin-induced diabetic mice. The effect of
      quercetin was compared with that of the classical antidepressants fluoxetine (5
      mg/kg, i.p.) and imipramine (15 mg/kg, i.p.). Streptozotocin-induced diabetic
      mice exhibited prolonged immobility duration during the test as compared with age
      matched control mice. Quercetin dose-dependently reduced the immobility period in
      diabetic mice, and this effect was comparable to that of fluoxetine (5 mg/kg,
      i.p.) and imipramine (15 mg/kg, i.p.). Fluoxetine and imipramine significantly
      lowered the immobility time in naive mice also, but quercetin failed to induce
      any antidepressant activity in naive mice. The results of our preliminary study
      indicate that quercetin has the potential to be employed as a therapy for
      depression associated with diabetes.

PMID- 14977451
TI  - Improvement of HDL- and LDL-cholesterol levels in diabetic subjects by feeding
      bread containing chitosan.
AB  - In this work we evaluated the efficacy and safety of a bread formulation
      containing chitosan in dyslipidemic type 2 diabetic subjects. For this purpose a
      total of 18 patients were allowed to incorporate to their habitual diets 120
      g/day of bread containing 2% (wt/wt) chitosan (chitosan group, n= 9) or standard
      bread (control group, n= 9). Before the study and after 12 weeks on the modified
      diet, the following parameters were evaluated: body weight, plasma cholesterol,
      high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)
      cholesterol, triglyceride, and hemoglobin A(1c) (HbA(1c)). Compared with the
      control group, the patients receiving chitosan-containing bread decreased their
      mean levels of LDL-cholesterol and significantly increased their mean levels of
      HDL-cholesterol at the end of the study. There were no significant differences in
      the body weight, serum triglyceride, and HbA(1c). These results suggest that
      chitosan incorporated into bread formulations could improve the lipoprotein
      balance similar to typical biliary salts trappers, increasing the HDL- and
      lowering the LDL-cholesterol, without changing the triglyceride levels. These
      results warrant further studies over a longer period of time to evaluate if a
      persistent improvement in levels of lipoproteins can be attained with this
      strategy.

PMID- 14977452
TI  - Antibacterial activity of Aristolochia bracteata root extracts.
AB  - Aristolochia bracteata (Aristolochiaceae) is used in traditional medicines as a
      gastric stimulant and in the treatment of cancer, lung inflammation, and
      dysentery and snake bites. The present investigation was undertaken to evaluate
      the antibacterial activity of Aristolochia bracteata root extracts. Roots of A.
      bracteata were powdered and successively extracted with ethyl acetate, acetone,
      methanol, and water for 8 hours each using a Soxhlet extractor. Antibacterial
      activity of dried extracts was evaluated by the pour-plate method against a few
      Gram-positive and Gram-negative bacteria. All the crude extracts showed a broad
      spectrum of antibacterial activity. The ethyl acetate extract was found to be the
      most effective. This study shows the potential for replacement of synthetic
      preservatives by the use of natural extracts.

PMID- 14977453
TI  - Psychopharmacology news.

PMID- 14977454
TI  - Clinical case presentation: therapeutic challenges in adolescent-onset bipolar
      disorder.

PMID- 14977455
TI  - The real cost of pediatric bipolar disorder.

PMID- 14977456
TI  - Commentary on Dr. Walkup's guest editorial.

PMID- 14977457
TI  - Pediatric bipolar disorder: the new perspective on severe mood dysfunction in
      children.

PMID- 14977458
TI  - Defining a developmental subtype of bipolar disorder in a sample of nonreferred
      adults by age at onset.
AB  - OBJECTIVE: To test the hypothesis that the age at onset of bipolar disorder would
      identify a developmental subtype of bipolar disorder in adults characterized by
      increased levels of irritability, chronic course, rapid cycling, and comorbidity
      with attention deficit hyperactivity disorder. METHODS: Forty-four adult subjects
      diagnosed with bipolar disorder were selected from large family studies of youth
      with and without attention deficit hyperactivity disorder. These subjects were
      stratified by the age at onset in childhood (younger than 13 years; n = 8, 18%),
      adolescence (13-18 years; n = 12, 27%, or adulthood (older than 19 years; n = 24,
      55%). All subjects were administered structure diagnostic interviews and a brief
      cognitive battery. RESULTS: In contrast with adult-onset bipolar disorder, child
      onset bipolar disorder was associated with a longer duration of illness, more
      irritability than euphoria, a mixed presentation, a more chronic or rapid-cycling
      course, and increased comorbidity with childhood disruptive behavior disorders
      and anxiety disorders. CONCLUSION: Stratification by age at onset of bipolar
      disorder identified subgroups of adult subjects with differing clinical
      correlates. This pattern of correlates is consistent with findings documented in
      children with pediatric bipolar disorder and supports the hypothesis that child
      onset bipolar disorder may represent a developmental subtype of the disorder.

PMID- 14977459
TI  - A preliminary study of the Kiddie Schedule for Affective Disorders and
      Schizophrenia for School-Age Children mania rating scale for children and
      adolescents.
AB  - OBJECTIVE: To construct a mania rating scale designed for children and
      adolescents. METHODS: Fourteen questions from the Kiddie Schedule for Affective
      Disorders and Schizophrenia for School-Age Children-Present Episode (K-SADS-P)
      1986 version plus a new item assessing mood lability were used to construct a
      clinician-rated mania rating scale (K-SADS-MRS). Interrater reliability was
      determined prospectively with 22 patients from a bipolar outpatient clinic.
      Sensitivity to treatment effects was determined in a separate cohort of 23
      patients. RESULTS: Internal consistency (Cronbach's alpha = 0.94) and interrater
      reliability (intraclass correlation coefficient = 0.97 between two raters) were
      high. Convergent validity with the Clinical Global Impressions-Severity scale
      (bipolar version) was good (r(s)= 0.91, p < 0.001). Treatment responders had
      significantly greater reduction in K-SADS-MRS scores than nonresponders (-15.6 +/
      8.7 vs. 0.3 +/- 8.8), t(21) = 4.2, p < 0.001. The K-SADS-MRS scores
      differentiated bipolar patients who had clinically significant manic symptoms
      from those who did not, with a sensitivity of 87% and a specificity of 81%.
      CONCLUSION: The K-SADS-MRS shows promise as a rating scale for measuring manic
      symptom severity in pediatric bipolar patients.

PMID- 14977460
TI  - Employing parent, teacher, and youth self-report checklists in identifying
      pediatric bipolar spectrum disorders: an examination of diagnostic accuracy and
      clinical utility.
AB  - The diagnosis of bipolar spectrum disorders (BPSD) is difficult to evaluate in
      child and adolescent populations. The current study examines whether commonly
      used behavior checklists- the Child Behavior Checklist, Teacher Report Form, and
      the Youth Self-Report form-are clinically useful in making a differential
      diagnosis between BPSD and other disorders. This study is the first to
      investigate the validity of integrating pairs of informants using these
      instruments to differentiate individuals with BPSD from those with disruptive
      behavior disorders, major depressive disorder, and any child or adolescent not
      meeting criteria for BPSD. Parent report best predicted diagnostic status, yet
      diagnostic efficiency statistics associated with these checklists were relatively
      poor. Results indicate that the Child Behavior Checklist has limited utility when
      attempting to derive clinically meaningful information about the presentation of
      juvenile BPSD.

PMID- 14977461
TI  - Mania in six preschool children.
AB  - At least nine cases of apparent preschool manic-depressive illness have been
      previously reported in the literature. In each of these children, a strong family
      history of affective illness was noted. In this report, the case histories of six
      preschool children ages 3 to 5 years with bipolar illness are summarized. These
      six were obtained from a sample of 36 consecutively hospitalized preschool
      children. Thus 17% of these hospitalized preschool children had bipolar illness.
      All had irritable mood, strong family history of affective illness, and previous
      presentation with symptoms of attention deficit hyperactivity disorder. They were
      diagnosed following a thorough clinical interview. Five children were treated
      with lithium; all five improved. Preschool mania exists as an identifiable entity
      and may respond to classic pharmacologic treatments.

PMID- 14977462
TI  - Patterns of comorbidity and dysfunction in clinically referred preschool and
      school-age children with bipolar disorder.
AB  - OBJECTIVE: Despite its common onset in preschool years, few studies have examined
      the characteristics of bipolar disorder (BPD) in preschoolers. This study reports
      on the clinical characteristics, psychiatric comorbidity, and functioning of
      preschoolers identified with BPD who were referred to a pediatric psychiatric
      clinic. METHODS: Structured psychiatric interviews assessing lifetime
      psychopathology by Diagnostic and Statistical Manual of Mental Disorders (third
      edition, revised) criteria were completed with parents about their children and
      confirmed by clinical interview of the child. Family, social, and overall
      functioning were also assessed at intake. Findings from preschoolers ages 4 to 6
      years were compared with a group of children ages 7 to 9 years (school age).
      RESULTS: We identified 44 preschoolers and 29 consecutively ascertained school
      age youth with BPD. Preschoolers had similar rates of comorbid psychopathology
      compared to school-age youth with BPD. Preschoolers and school-age children with
      BPD typically manifest symptoms of mania and major depression simultaneously
      (mixed states). Both preschoolers and school-age children had substantial
      impairment in school, social, and overall functioning. CONCLUSIONS: These results
      suggest that clinically referred preschoolers with BPD share with school-age
      children with BPD high rates of comorbid psychopathology and impaired
      functioning. Follow-up of these clinically referred preschoolers with BPD
      evaluating the stability of their diagnoses, treatment response, and their long
      term outcome is necessary.

PMID- 14977463
TI  - Clinical correlates of episodicity in juvenile mania.
AB  - OBJECTIVE: Researchers debate whether the diagnostic criteria for mania should
      differ between children and adults. Specifically, although the Diagnostic and
      Statistical Manual of Mental Disorders (fourth edition; DSM-IV) requires episodic
      mood changes, children commonly are diagnosed as manic on the basis of chronic
      irritability. In this preliminary study, children carrying a diagnosis of bipolar
      disorder (BPD) in the community were classified as having either episodic or
      chronic symptoms. We hypothesized that the episodic group would be more likely to
      have a history of psychosis and a parental history of BPD, whereas the chronic
      group would be more likely to have conduct disorder. METHODS: Parents of children
      carrying the BPD diagnosis were interviewed on the telephone to obtain
      psychiatric and family histories. Children were considered episodic (n = 34) if
      they had a history of one or more DSM-IV manic/hypomanic episodes meeting full
      duration criteria and chronic (n = 53) if they had no discernable episodes.
      RESULTS: The episodic group was more likely to have had psychosis, parental
      history of BPD, and to have experienced each manic symptom except for
      irritability and psychomotor agitation. Children in the episodic group were also
      more likely to have had a depressive episode meeting full DSM-IV criteria and
      were more likely to have made a suicide attempt. Children in the chronic group
      were not more likely to meet criteria for conduct disorder but were more likely
      to exhibit violence toward others. CONCLUSIONS: These preliminary data indicate
      that, among children being treated for BPD in the community, those with discrete
      episodes of mania may be more likely to have a lifetime history of psychosis and
      a parental history of BPD. The latter hypothesis should be tested in a sample
      where relatives are interviewed directly.

PMID- 14977464
TI  - Medication use in children and adolescents treated in the community for bipolar
      disorder.
AB  - We assessed the use of mood stabilizers, stimulants, antipsychotic medication,
      and selective serotonin reuptake inhibitors in children being treated in the
      community for bipolar disorder (BPD). One hundred eleven patients were screened
      via parent phone interview for possible inclusion in a phenomenological study of
      BPD. Data were obtained on the patients' medication trials and side effects. The
      results of the study indicated that children and adolescents who carry a
      diagnosis of BPD are treated with a mean of 3.40 +/- 1.48 medications and have
      had a mean of 6.32 +/- 3.67 trials of psychotropic medication in the past. Ninety
      eight percent have had a trial of a mood stabilizer or anticonvulsant, with the
      most common being valproate (79%), lithium (51%), and gabapentin (29%).

PMID- 14977465
TI  - Long-term outcome with divalproex in children and adolescents with bipolar
      disorder.
AB  - OBJECTIVE: To assess the outcome and safety of divalproex treatment in children
      and adolescents with bipolar disorder. METHODS: We conducted a chart review of
      children and adolescents who were treated with divalproex and who met Diagnostic
      and Statistical Manual of Mental Disorders, fourth edition, criteria for bipolar
      disorder (dose 966 +/- 501 mg/day, level 79.4 +/- 23.1 micro g/mL, duration 1.4
      +/- 1.5 years). Responders were defined as those showing moderate to marked
      response on the Clinical Global Impression-Improvement (CGI-I) scale. RESULTS:
      Eight of 15 (53%) patients responded to divalproex treatment for mixed episode (n
      = 6), disruptive behavior (n = 4), pure mania (n = 3), or depression (n = 2). Six
      of 15 (40%) discontinued divalproex, most due to side effects (n = 5). The most
      common side effect was weight gain (4/15, 27%). CONCLUSION: In children aged 4-18
      years, divalproex treatment was related to improved outcome in the long-term
      treatment of bipolar disorder. One third of the patients discontinued treatment
      secondary to side effects, including a case of reversible liver enzyme elevation.

PMID- 14977466
TI  - Temperament and character factors in a prepubertal and early adolescent bipolar
      disorder phenotype compared to attention deficit hyperactive and normal controls.
AB  - OBJECTIVE: To compare temperament and character (T/C) factors in a prepubertal
      and early adolescent bipolar disorder phenotype (PEA-BP), attention deficit
      hyperactivity disorder (ADHD), and normal community controls (NC). METHODS:
      Subjects in PEA-BP (n = 101), ADHD (n = 68), and NC (n = 94) groups were
      diagnostically assessed with the Washington University in St. Louis Kiddie
      Schedule for Affective Disorders and Schizophrenia given separately to mothers
      about their children and to children about themselves. Diagnosis of PEA-BP was
      defined as Diagnostic and Statistical Manual of Mental Disorders, fourth edition,
      bipolar disorder (manic or mixed phase) with at least one cardinal symptom of
      mania (i.e., elation and/or grandiosity) to avoid diagnosing mania by symptoms
      that overlapped with those for ADHD. The Junior Temperament and Character
      Inventory (JTCI) was used to measure T/C factors. Separate JTCI data were
      obtained from mothers about their children and from children about themselves.
      RESULTS: Parent- and child-reported novelty seeking were significantly higher in
      PEA-BP than in NC subjects. Novelty seeking was significantly higher in the ADHD
      group than in the NC group only by parent report. Parent and/or child report
      showed PEA-BP and ADHD subjects to be significantly less reward-dependent,
      persistent, self-directed, and cooperative than NC subjects. Parent-reported
      cooperativeness was significantly lower in PEA-BP than in ADHD subjects.
      CONCLUSION: These findings are consistent with studies of novelty seeking in
      adults who had either BP or ADHD and are discussed in relationship to genetic
      studies of dopamine receptors and novelty seeking.

PMID- 14977467
TI  - Proton magnetic resonance spectroscopy of the frontal lobe and cerebellar vermis
      in children with a mood disorder and a familial risk for bipolar disorders.
AB  - OBJECTIVE: Few studies have examined the neurochemical abnormalities that might
      be associated with pediatric bipolar disorder. The aim of this study was to use
      magnetic resonance spectroscopy to evaluate several brain regions implicated in
      bipolar disorder in children with a mood disorder and a familial risk for bipolar
      disorder. We hypothesized that these children would exhibit neurochemical
      differences compared with healthy children of parents without a psychiatric
      disorder. Specifically, decreased N-acetylaspartate (NAA) and creatine and
      phosphocreatine (Cr) of the prefrontal cortex and cerebellar vermis would reflect
      impairments in neuronal function and cellular metabolism, and elevated myo
      inositol (mI) would reflect impaired phosphoinositide metabolism, potentially
      representing early markers of neurophysiologic changes that might underlie the
      development of bipolar disorder. METHODS: Children with a mood disorder and at
      least one parent with bipolar disorder (n = 9) and healthy children (n = 10)
      group matched for age (8-12 years), race, sex, education, and Tanner stage were
      evaluated using the Washington University in St. Louis Kiddie Schedule for
      Affective Disorders and Schizophrenia. Proton magnetic resonance spectroscopy was
      acquired using 8-cc volumes within the frontal cortex, frontal white matter, and
      the cerebellar vermis. Metabolite ratios (NAA/Cr, cholines (Cho)/Cr, mI/Cr,
      NAA/Cho, NAA/mI, and Cho/mI) and concentrations (NAA, Cr, Cho, and mI) were
      calculated and compared between groups. RESULTS: The trend in concentration
      levels of NAA and Cr was approximately 8% lower for children with a mood disorder
      than healthy children within the cerebellar vermis. The frontal cortex in
      children with a mood disorder revealed elevated mI concentration levels,
      approximately 16% increased, compared with healthy children. CONCLUSIONS: Similar
      to findings in adults with bipolar disorders, neurochemical abnormalities within
      the frontal cortex and the cerebellar vermis were present in this preliminary
      comparison of children with a mood disorder and a familial risk for bipolar
      disorder. Larger sample sizes are needed to replicate these findings.

PMID- 14977468
TI  - Neural stem cells: one of the keys to everything.

PMID- 14977469
TI  - Adventures in clinical and basic science.

PMID- 14977470
TI  - Multiorgan engraftment and multilineage differentiation by human fetal bone
      marrow Flk1+/CD31-/CD34- Progenitors.
AB  - We previously reported that Flk1(+)/CD31(-)/CD34(-) cells isolated from human
      fetal bone marrow can differentiate at the single cell level into endothelial and
      hematopoietic cells in vitro. Here we report that within this cell population
      reside cells that can differentiate into the epithelium of liver, lung, gut, as
      well as the cells of both hematopoietic and endothelial system after primary or
      secondary transplantation into irradiated nonobese diabetic/severe combined
      immunodeficient (NOD/SCID) mice. Hence, Flk1(+)/CD31(-)/CD34(-) cells possess
      remarkable differentiation potential and may thereby provide an alternative to
      hematopoietic stem cells for transplantation. In addition, our results show this
      stem cell population effectively accelerated wound healing in NOD/SCID mice and
      thus holds therapeutic promise for treatment of genetic disorders, organ
      dysfunction, and tissue repair in humans.

PMID- 14977471
TI  - Neural stem cell therapy in the aging brain: pitfalls and possibilities.
AB  - As aging progresses, there is a decline in the brain's capacity to produce new
      neurons in the two neurogenic regions, the subventricular zone surrounding the
      lateral ventricles and the subgranular layer of the hippocampal dentate gyrus.
      The underlying cause of the declining neurogenesis is unknown, but is presumably
      related to age-related changes that occur during normal aging of the brain. It is
      exacerbated by age-related neurodegenerative diseases such as Alzheimer's and
      Parkinson's diseases. Stem cell-based therapy to replace lost and/or damaged
      cells in the aging brain is currently the focus of intense research. The two most
      promising approaches involve transplantation of exogenous tissue and promoting
      proliferation of endogenous cells. However, age-related changes in the brain
      environment, including elevated oxidative stress and accumulation of protein and
      lipid by-products, present several unique challenges that must be addressed
      before cell-based therapy can be used as a viable option. Although progress has
      been made toward replacement of lost cells and recovery of lost function, there
      are fundamental issues that need to be addressed for stem cell therapy to be
      successful in the aging brain. In this review, we focus on recent progresses made
      toward understand the biology of neural stem cells in the aging brain, as well as
      progress toward using stem cells to replace cells lost during disease.

PMID- 14977472
TI  - Embryonic stem cells for neural replacement therapy: prospects and challenges.
AB  - Injury or degeneration of the vertebrate central nervous system often disrupts
      neuronal circuitry that is built by projection neurons during early embryonic
      life. Repair of neural network through regeneration of these early-born
      projection neurons in adult life often fails since stem cells residing in the
      adult brain are generally programmed to give rise to late-born interneurons.
      Thus, exogenous cells are needed to rebuild the neural circuitry. Nevertheless,
      cell replacement in the brain remains a challenging goal because of the lack of
      safe and effective donor cells, as well as difficulty in remodeling the
      nonneurogenic adult CNS environment. Here I will concentrate on the donor side
      and discuss how recent advancement in stem cell technology offers hope for
      transplant therapy, with a focus on the potentials and hurdles of human embryonic
      stem cells as a sustainable source.

PMID- 14977473
TI  - The future of cell-based transplantation therapies for neurodegenerative
      disorders.
AB  - Parkinson's disease is a common neurodegenerative disease with a lifetime
      incidence of 2.5% and a prevalence of at least 2% in individuals over 70 years
      old. Patients can be effectively treated with drugs that target the dopaminergic
      nigro-striatal pathway, but over time the efficacy of these medications is
      limited by the development of profound motor fluctuations and dyskinesias. This
      has prompted the search for alternative treatments, including the use of cell
      replacement therapies. Over the last decade, human fetal nigral transplants have
      demonstrated that dopaminergic neurons can survive and provide clinical benefit
      for patients with Parkinson's disease. However, there are clearly ethical
      concerns and a limit to the supply of this tissue as well as more recently
      anxieties over side effects. As a result, alternative sources of tissue have been
      investigated, and one such source are stem cells, which provide an attractive
      renewable tissue supply. In this review, we will discuss the current state-of-the
      art and the characteristics of Parkinson's disease that increase its attraction
      as a target of stem cell therapy against results of current clinical trials using
      fetal neural grafts. Then we will discuss the various types and sources of stem
      cells, and some early transplantation results in animal models of Parkinson's
      disease. Finally we will discuss the prospect of using stem cells to deliver
      drugs and neurotrophic factors involved in neuroprotective and neuroreparative
      strategies in Parkinson's disease and other neurodegenerative conditions.

PMID- 14977474
TI  - A new concept of stem cell disorders and their new therapy.
AB  - The author previously proposed a new concept of categorizing stem cell disorders
      as: (1) stem cell aplasia (aplastic anemia), (2) monoclonal hematopoietic stem
      cell proliferative syndrome (leukemia and myelodysplastic syndrome), and (3)
      polyclonal hemopoietic stem cell proliferative syndrome (systemic and organ
      specific autoimmune diseases). This review includes the following two stem cell
      disorders: mesenchymal stem cell disorders and organ-specific stem cell
      disorders. Age-associated diseases such as Alzheimer's disease, osteoporosis, and
      lung fibrosis belong to the former, whereas carcinosarcoma in the lung and adeno
      endocrine cell carcinoma in the stomach belong to the latter. Recently, we have
      established a new method for allogeneic bone marrow transplantation using
      chimerism-resistant autoimmune-prone MRL/lpr mice. In this method, whole bone
      marrow cells containing a small number of T cells and mesenchymal stem cells are
      directly injected into the bone marrow cavity. MRL/lpr mice treated by injection
      of stem cells survived more than 2 years without showing symptoms of autoimmune
      disease. To apply this method to humans, we established a new method for bone
      marrow cell harvesting using cynomolgus monkeys. In this method, cells are
      harvested from the long bones using a perfusion method and are then injected
      directly into the bone marrow cavity of recipients. In this review, we show that
      this new method may become a powerful strategy for the treatment of various
      intractable diseases.

PMID- 14977475
TI  - Neural stem cells in the adult nervous system.
AB  - The concept of the immutability of the nervous tissue has recently been replaced
      with the new idea that a continuous neurogenic turnover does occur in some
      limited areas of the central nervous system (CNS). At least two neurogenic
      regions of the adult mammalian CNS are involved in this process: the
      subventricular zone of the forebrain and the dentate gyrus of the hippocampus,
      which are considered to be a reservoir of new neural cells. Neural stem cells
      (NSCs) are multipotential progenitors that have self-renewal capability. While in
      vivo endogenous NSCs seem able to produce almost exclusively neurons, a single
      NSC in vitro is competent to generate neurons, astrocytes, and oligodendrocytes.
      NSCs lack a specific morphology and unambiguous surface markers that could allow
      their identification. For this reason, one of the major difficulties in
      identifying stem cells is that they are defined in terms of their functional
      capabilities, the determination of which might alter the cells' nature. The
      purpose of this review is to describe the characteristics of the NSCs of the
      adult mammalian CNS, their potentiality in terms of proliferation and
      differentiation capabilities, as well as their stability in long-term culture,
      all attributes that make them a good tool for tissue replacement therapies.

PMID- 14977476
TI  - Adult neural stem cells and repair of the adult central nervous system.
AB  - Neural stem cells are present not only in the developing nervous systems, but
      also in the adult central nervous system of mammals, including humans. The mature
      central nervous system has been traditionally regarded as an unfavorable
      environment for the regeneration of damaged axons of mature neurons and the
      generation of new neurons. In the adult central nervous system, however, newly
      generated neurons from adult neural stem cells in specific regions exhibit a
      striking ability to migrate, send out long axonal and dendritic projections,
      integrate into pre-existing neuronal circuits, and contribute to normal brain
      functions. Adult stem cells with potential neural capacity recently have been
      isolated from various neural and nonneural sources. Rapid advances in the stem
      cell biology have raised exciting possibilities of replacing damaged or lost
      neurons by activation of endogenous neural stem cells and/or transplantation of
      in vitro-expanded stem cells and/or their neuronal progeny. Before the full
      potential of adult stem cells can be realized for regenerative medicine, we need
      to identify the sources of stem cells, to understand mechanisms regulating their
      proliferation, fate specification, and, most importantly in the case of neuronal
      lineages, to characterize their functional properties. Equally important, we need
      to understand the neural development processes in the normal and diseased adult
      central nervous system environment, which is quite different from the embryonic
      central nervous system, where neural development has been traditionally
      investigated. Here we will review some recent progress of adult neural stem cell
      research that is applicable to developmental neurobiology and also has potential
      implications in clinical neuroscience.

PMID- 14977477
TI  - Postnatal astrocytes promote neural induction from adult human bone marrow
      derived stem cells.
AB  - Neural stem cells (NSCs) have generated considerable interest because of their
      potential as a source of defined cells for drug screening or cell-based therapies
      for neurodegenerative diseases. Ethical and practical considerations limit the
      availability of human fetal-derived neural tissue and highlight the need to
      consider alternative sources of human NSCs. Because of their ready availability,
      their ability to be easily expanded, and reports of neural potential, bone marrow
      derived populations have become the focus of intense study with regard to their
      potential clinical utility. However, recent identification of spontaneous cell
      fusion and limited neuronal differentiation has tempered initial optimism. In
      this study, we demonstrate the monoclonal neural and mesodermal potential of
      adult human bone marrow mesenchymal cells. Critically, we show that sequential
      treatment with the mitogens epidermal growth factor (EGF) and fibroblast growth
      factor-2 (FGF-2) followed by postnatal hippocampal astrocyte conditioned medium
      significantly promotes the generation of neurofilament(+)/beta-tubulin(+) cells
      from bone marrow precursors. The ability to generate almost limitless numbers of
      neural precursors from a readily accessible autologous adult human source
      provides a platform for further studies and potentially has important therapeutic
      implications.

PMID- 14977478
TI  - Artificial niches for human adult neural stem cells: possibility for autologous
      transplantation therapy.
AB  - Cellular transplantation therapy is thought to play a central role in the concept
      of restorative neurosurgery, which aims to restore function to the damaged
      nervous system. Stem cells represent a potentially renewable source of
      transplantable cells. However, control of the behavior of these cells, both in
      the process of clonogenic expansion and post-transplantation, represents
      formidable challenges. Stem cell behavior is thought to be directed by
      extracellular signals in their in vivo niches, many of which are protein or
      peptide based. As only one example, activation of Notch plays an important role
      in normal development and is the strongest known signal for stem cells to choose
      glial over neuronal fates. Therefore, artificial extracellular matrix proteins
      represent a potentially powerful tool to custom design artificial niches to
      strategically control stem cell behavior. We have developed a family of aECM
      proteins that incorporate the active domains of the DSL ligands to the Notch
      receptor into an elastin-based backbone. The development of our DSL-elastin
      artificial proteins demonstrates the design strategy and methodology for the
      production of bioactive artificial extracellular matrix proteins aimed at
      modulating stem cell behavior, and this method can be used to design other
      bioactive aECM proteins. In addition, we have developed a method for the
      isolation and characterization of adult human neural stem cells from
      periventricular tissue harvested from living patients. This paper reviews
      cellular transplantation therapy from the clinical perspective and summarizes
      ongoing work aimed at exploring the intriguing possibility of autologous
      transplantation, whereby neural stem cells can be harvested from adult patients,
      expanded or modified in vitro in artificial niches, and retransplanted into the
      original patient.

PMID- 14977479
TI  - High-dose immunosuppression and autologous hematopoietic stem cell rescue for
      severe multiple sclerosis.
AB  - Multiple sclerosis is a relatively common and seriously disabling disease of
      autoimmune pathogenesis, for which there is currently no cure. Available
      therapies include immunomodulating agents and standard-dose immunosuppressants,
      which may be helpful but are not curative. Recently, studies in animal models
      have indicated that control of autoimmune disease can be obtained by high-dose
      immunosuppression followed by hematopoietic stem cell transplantation (rescue).
      Autologous transplants for severe and refractory multiple sclerosis were proposed
      in 1997 and have been performed ever since in selected patients and in the
      context of phase I/II trials. To date, more than 200 patients have been treated
      worldwide, and similar results were obtained in different centers: high-dose
      therapy suppresses inflammation in the brain to a degree superior to any other
      conventional therapy and seems to delay significantly clinical disease
      progression. There is, however, a procedure-related mortality risk of 1.5-5%,
      requiring careful patient selection before transplant. The treatment should be
      reserved for patients having high chance of response, i.e., young patients with
      low disability scores but rapidly progressing disease, having inflammatory rather
      than neurodegenerative changes in the central nervous system. The mechanism of
      action of transplantation is unclear. The initial concept of immune ablation by
      high-dose therapy and reconstitution of normal immunity from transplant-derived
      lymphocyte progenitors has given way to the concept of "resetting" the immune
      system and of bringing the disease to a lower level of activity. One could also
      speculate on a tissue repair effect, given the ability of human hematopoietic
      stem cells to migrate also into the central nervous system. The clinical effect
      of transplantation remains to be demonstrated in a randomized study. The
      Autoimmune Disease Working Party of the European Group for Blood and Marrow
      Transplantation has launched such a trial, comparing transplantation to the
      currently best available therapy, i.e., mitoxantrone, and in about 5 years we
      should know whether transplantation offers more than the benefit of a transient
      immunosuppressive effect.

PMID- 14977480
TI  - Embryonic neural progenitor cells: the effects of species, region, and culture
      conditions on long-term proliferation and neuronal differentiation.
AB  - One of the major obstacles to the use of neural stem/progenitor cells in neuronal
      replacement therapy is the limited ability of these cells to generate sufficient
      numbers of specific neuronal phenotypes either in the culture dish or after
      transplantation in animal models of neurodegenerative disease. It is not yet
      fully understood whether embryonic neural stem and progenitor cells show species
      specific or regional identities, or if current culture paradigms select for a
      particular subset of stem cells/progenitors with similar proliferation and
      differentiation capacities. To investigate this issue, we isolated embryonic
      neural progenitors derived from the developing rat and mouse central nervous
      system for in vitro culture to assess the regional, species-specific, and
      temporal effects on both cell proliferation and generation of neurons.
      Neurosphere cultures were derived from E13-15 mouse or rat developing striatum
      (medial, lateral, or whole ganglionic eminence), ventral mesencephalon, and
      cortex. We compared basic fibroblast growth factor and epidermal growth factor
      for their influence on cell proliferation and neuronal differentiation under
      defined differentiation paradigms. Seeding density and conditioned media were
      also tested for their effects on maintenance of cell proliferation over
      protracted time periods. Results showed that embryonic neural stem/progenitor
      cells maintained defined patterns of proliferation and neuronal differentiation,
      with both declining with time in vitro. Proliferation rate was more dependent on
      species and region than the neurotrophins or conditions used for culture. These
      results suggest that the appropriate selection of embryonic neural stem cells and
      culture conditions may be crucial for the optimization of their neurogenic
      potential.

PMID- 14977481
TI  - Neuronal differentiation of murine bone marrow Thy-1- and Sca-1-positive cells.
AB  - Recent evidence suggests that cells from bone marrow can acquire neuroectodermal
      phenotypes in cell culture or after transplantation in animal models and in the
      human brain. However, isolation of the bone marrow cell subpopulation with
      neuronal differentiation potential remains a challenge. To isolate and expand
      neural progenitors from whole murine bone marrow, bone marrow was obtained from
      hind limb bone of C57BL6 mice and plated in culture with neuronal medium with
      basic fibroblast growth factor and epidermal growth factor. After 5-7 days in
      culture, cellular spheres similar to brain neurospheres appeared either floating
      or attached to culture dishes. These spheres were collected, dissociated, and
      expanded. The bone marrow-derived spheres were positive for nestin as assessed by
      immunocytochemistry and by reverse transcriptase polymerase chain reaction. Thy-1
      and Sca-1-positive bone marrow cells selected by magnetic cell sorting resulted
      in a higher yield of nestin-positive spheres. After exposure to neuronal
      differentiative medium retinoic acid with and without Sonic hedgehog, cells
      positive for neuronal markers tubulin III (TuJ-1) and neurofilament (NF) were
      detected. The mRNA profile of these cells included the expression of TuJ-1,
      neuronal-specific enolase (NSE), and NF-light chain. To evaluate the in vivo
      behavior of these cells, spheres derived from bone marrow-derived cells of
      transgenic green fluorescent protein (GFP) mice were transplanted into newborn
      mouse brain. Two months later, the mouse neural cortex contained a minor
      proportion of GFP(+) cells co-expressing neuronal markers (TuJ-1, NF, MAP-2,
      NeuN). Although cell fusion phenomena with the host cells could not be ruled out,
      bone marrow-derived neurosphere transplantation could be a strategy for cellular
      mediated gene therapy.

PMID- 14977482
TI  - Growth factor deprivation induces an alternative non-apoptotic death mechanism
      that is inhibited by Bcl2 in cells derived from neural precursor cells.
AB  - Although apoptosis has been considered the typical mechanism for physiological
      cell death, presently alternative mechanisms need to be considered. We previously
      showed that fibroblast growth factor-2 (FGF2) could act as a survival factor for
      neural precursor cells. To study the death mechanism activated by the absence of
      this growth factor, we followed the changes in cell morphology and determined
      cell viability by staining with several dyes after FGF2 removal from
      mesencephalic neural-progenitor-cell cultures. The changes observed did not
      correspond to those associated with apoptosis. After 48 h in the absence of FGF2,
      cells began to develop vacuoles in their cytoplasm, a phenotype that became very
      obvious 3-5 days later. Double-membrane vacuoles containing cell debris were
      observed. Vacuolated cells did not stain with either ethidium bromide or trypan
      Blue, and did not show chromatin condensations. Nonetheless, during the course of
      culture, vacuolated cells formed aggregates with highly condensed chromatin and
      detached from the plate. Neural progenitor cells grown in the presence of FGF2
      did not display any of those characteristics. The vacuolated phenotype could be
      reversed by the addition of FGF2. Typical autophagy inhibitors such as 3-MA and
      LY294002 inhibited vacuole development, whereas a broad-spectrum caspase
      inhibitor did not. Interestingly, Bcl-2 overexpression retarded vacuole
      development. In conclusion, we identified a death autophagy-like mechanism
      activated by the lack of a specific survival factor that can be inhibited by
      Bcl2. We propose that anti-apoptotic Bcl2 family members are key molecules
      controlling death activation independently of the cell degeneration mechanism
      used.

PMID- 14977483
TI  - The potential role of HLA-G polymorphism in maternal tolerance to the developing
      fetus.
AB  - The mechanism by which the developing fetus survives the maternal immunity has
      eluded investigators and remains a central paradox in the field of stem cell
      research. If the mechanism can be defined, allogenic stem cells may find
      increased utility after transplantation. While several theories have been
      advanced, the differential expression of HLA antigens on trophoblasts has been
      the focus of many studies. Interestingly, an inverse relationship between HLA-G
      (nonclassical class I molecules) and class I MHC gene expression exists early in
      pregnancy. HLA-G transcripts are present in quite significant amounts in first
      trimester placental tissue, particularly in the extravillous membranes, while the
      opposite occurs at term. This kind of expression is consistent with the theory
      that HLA-G might play a role in fetal protection. This could be consequent to
      either nonimmune (structural) or immune functions at the maternal-fetal
      interface. Current evidence suggest an immune function wherein HLA-G protects
      fetal cells from maternal uterine natural killer (NK) cells, which are found in
      large numbers within cells invading the trophoblasts. This effect has been
      attributed to maternal NK receptor alterations as well as inhibition of maternal
      NK cell traffic across the placenta. The recent identification of HLA-G
      polymorphism brings into play the potential role of these isoforms in fetal
      protection. Polymorphism may be associated with differential function or may
      effect linkage disequilibria with other HLA variants, providing fetal protection.

PMID- 14977484
TI  - Could the functional expression of HLA-G be exploited for successful stem cell
      transplantation and engraftment?

PMID- 14977485
TI  - The prospects for neuroprotection in MS.
AB  - In the past, neuroprotective therapies were mostly explored in neurodegenerative
      disorders like Parkinson's and Alzheimer's disease, and in ischaemic stroke. More
      recently, however, neuroprotection has been proclaimed an important goal for
      multiple sclerosis (MS) therapy. The basis for widening the scope of
      neuroprotection is evidence that neuronal and axonal injury are key features of
      MS lesions. In contrast with degenerative and ischaemic central nervous system
      injury, however, neurodegeneration in MS appears to be caused by an inflammatory,
      presumably autoimmune, process. The challenge for neuroprotection in MS is
      therefore greater than in degenerative and ischaemic disorders, because MS
      requires the combination of neuroprotective therapy and effective
      immunomodulation.

PMID- 14977486
TI  - Highlights of the Second International Conference on MS, May 2003, Dubrovnik,
      Croatia.
AB  - The conference was organized by Professors Vesna Brinar of the Faculty of
      Medicine, University of Zagreb, Croatia and Charles Poser of the Harvard Medical
      School, Boston, USA. It was attended by almost 200 neurologists from as far
      afield as South Africa and Russia. The major topics to be explored were: the
      natural history of multiple sclerosis (MS); development of diagnostic criteria;
      genetics with special emphasis on the 'MS trait'; pathogenesis with emphasis on
      repair; nomenclature of MS and its 'variants'; differentiation between MS and
      disseminated encephalomyelitis; diagnostic and therapeutic dilemmas resulting
      from MRI abnormalities in asymptomatic people; various treatments; and a general
      critique of therapeutic trials.

PMID- 14977487
TI  - B-cell immunity in MS.
AB  - T-cell-mediated immunity has dominated studies of multiple sclerosis (MS)
      pathogenesis, mainly due to detection of activated T-cells in MS lesions, and
      analogies with the animal model experimental allergic encephalomyelitis. The
      prevailing aetiological hypothesis is that MS is a multifactorial disorder,
      affecting individuals predisposed by a combination of susceptibility genes and
      environmental factors. Plaque formation is attributed to immune mechanisms,
      triggered by an autoimmune attack directed against antigens in the myelin
      membrane. This article reviews the roles of components of the immune response in
      MS including B-cells, the complement cascade, antibodies and genes. Evidence
      suggests that B-cell clonal expansion in cerebrospinal fluid and plaques of MS
      patients indicate an ongoing, antigen-driven response in the central nervous
      system. That MS is an autoimmune disease remains inconclusive, but the assumption
      is that humoral immunity plays a role in lesion formation and perpetuation, or is
      involved in tissue-repair mechanisms. The paradigm of MS as a T-cell disease must
      be revisited, as B-cells are involved during the initial and later disease
      stages, and evidence is mounting for a 'degenerative process', in addition to
      (and possibly even preceding) inflammation.

PMID- 14977488
TI  - Meeting Report: 10 Years of Progress: Report from Selected Presentations at the
      19th ECTRIMS Congress, 1720 September 2003, Milan, Italy.
AB  - The success of the European Committee for Treatment and Research in Multiple
      Sclerosis (ECTRIMS) is notable, and Chris Polman (Amsterdam, the Netherlands),
      the new President of ECTRIMS, pointed out that the Congress had grown from an
      attendance of 50 delegates in 1982 to over 3000 at this 19th meeting. ECTRIMS
      2003 provided an overview of recent achievements in clinical multiple sclerosis
      (MS) research, with sessions highlighting understanding and promoting functional
      and structural recovery, and the necessity and progress made in co-ordinating
      research efforts in MS. The impact of molecular biology, new perspectives in MRI
      and advances in treatment were covered in comprehensive reviews and original
      presentations. Five hundred stimulating posters from researchers around the world
      were also presented. Several satellite symposia, a young scientific
      investigators' session, an international workshop on remyelination in MS, a
      comprehensive exhibition and presentations of late-breaking research complemented
      the main programme.

PMID- 14977489
TI  - Immune-mediated neurodegeneration and neuroprotection in MS.
AB  - It has become evident that multiple sclerosis (MS) has significant
      neurodegenerative components. An increasing number of reports show neuronal and
      axonal damage in MS patients and experimental allergic encephalomyelitis (EAE) in
      an animal model of MS. The mechanisms behind this neurodegeneration are unknown,
      but evidence suggests immune-mediated damage. In this review we analyse the
      findings of immune-mediated injury in MS and focus on axonal and neuronal injury.
      The potential neuroprotective role of some currently available MS drug treatments
      is also discussed.

PMID- 14977490
TI  - Vancouver Consortium of MS Centers' Magnetic Resonance Imaging Guidelines.
AB  - The increasing use of magnetic resonance imaging (MRI) as a diagnostic tool for
      multiple sclerosis (MS) as recently enforced in the McDonald committee criteria-
      and the importance of MRI measurements in therapeutic studies both demonstrate
      the value of MRI findings. MRI aids our understanding of MS and management of
      patients.

PMID- 14977491
TI  - Interferons in relapsing remitting MS: a systematic review comments on a meta
      analysis.
AB  - The multiple sclerosis (MS) community read recently, with some surprise, the
      conclusions from a systematic review of the major therapeutic recombinant
      interferon trials in relapsing-remitting (RR)MS.1 The review stated that: 'their
      (recombinant interferons) clinical effect beyond 1 year is uncertain and new
      trials are needed to assess their long-term effectiveness.'. If neurologists
      agree that these compounds have a moderate effect, but that the effect needs to
      be confirmed in long-term (510 year) trials, patients and their doctors deserve
      an explanation rather than a damning statement.

PMID- 14977492
TI  - Seasonal epidemic of ocular caterpillar hair injuries in the Kangra District of
      India.
AB  - PURPOSE: To report a rare seasonal occurrence of ocular caterpillar hair injuries
      (ophthalmia nodosa) in epidemic proportions in the Kangra district of Himachal
      Pradesh, India. METHODS: 136 patients with pain, redness and a foreign body
      sensation in their eyes were examined and treated for caterpillar hair injury in
      a short span of 6 months. RESULTS: The pattern of corneal abrasions was very
      useful in indicating the presence and location of the setae. All the cases
      resolved with no sequelae. The intra-corneal hair remained inert on long term
      follow-up. CONCLUSIONS: Creating awareness about these injuries among the medical
      staff and the general public is necessary for proper control and management.

PMID- 14977493
TI  - Trachoma among adults in Damot Gale District, South Ethiopia.
AB  - PURPOSE: To determine the prevalence of trachoma and its risk factors among
      adults in the Damot Gale District of south Ethiopia. METHODS: A cross-sectional,
      community based survey was conducted in the Damot Gale District of south
      Ethiopia. A multi-stage sampling method was used to select subjects. RESULTS: Out
      of 924 eligible subjects, 855 were examined, for a response rate of 92.5%. Active
      trachoma [follicles (TF), intense inflammation (TI) or TF/TI] was found in 20.6%
      (95% CI: 17.8-23.4%) of the subjects. The prevalence of trachomatous trichiasis
      (TT) and corneal opacity (CO) was 6.8% (95% CI: 5.1-8.5%) and 2.1% (95% CI: 1.0
      3.1%), respectively. Females were affected by active trachoma twice as often as
      males [OR 2.13 (95% CI: 1.67-3.50, P<0.0001)]. The prevalence of blinding
      trachoma (TT and CO) was also significantly higher among females [OR 3.03 (95%
      CI: 1.58-5.89, P<0.001)]. Literacy and face washing were found to be
      significantly associated with less prevalence of active trachoma. CONCLUSION: The
      prevalence of both active and cicatricial trachoma among adults residing in the
      Damot Gale District of south Ethiopia is very high. Although children are the
      main reservoirs of active trachoma, intervention strategies should address the
      fact that a high prevalence of active trachoma is also found among adults
      residing in hyperendemic areas.

PMID- 14977494
TI  - Economic and quality-of-life impact of seasonal allergic conjunctivitis in
      Oxfordshire.
AB  - PURPOSE: The purpose of this study was to examine the economic and quality-of
      life (QoL) impact of seasonal allergic conjunctivitis (SAC) from the individual
      patient perspective. SETTING: The study population was drawn from the general
      public of Oxfordshire, England. METHODS: Participants were recruited from either
      general practices or the casualty department of the Oxford Eye Hospital (OEH).
      All persons who were between 16 and 80 years of age and English speaking were
      eligible for enrollment in the study. The inclusion criteria for cases was that
      participants: 1) experienced itchy, bloodshot and watering eyes at some time
      between February and August every year since 1999, and 2) considered it likely
      that this was in response to seasonal allergens. Controls were drawn from the
      same sources and were age- and sex-matched to cases. Participants completed the
      EQ-5D Health Questionnaire, the Rhinoconjunctivitis Quality of Life Questionnaire
      (RQLQ), the National Eye Institute (U.S.) Visual Functioning Questionnaire 25
      (VFQ-25), and a specially developed Health Economic and Demographic
      Questionnaire. RESULTS: Most participants in both groups were female (67.5% in
      the SAC and 70% in the control group, P=0.565). Weekly earnings were lower in the
      SAC group (P<0.001), as the SAC group also worked fewer hours per week (P<0.001).
      Participants with SAC also experienced a greater degree of pain and discomfort as
      measured by the EQ-5D (P=0.018) and a lower perception of health using the EQ-VAS
      (P=0.039). Statistically significant differences between both groups were
      detected in all domains of the VFQ-25, except general and colour vision, although
      the differences were thought to be clinically significant only for the ocular
      pain domain. The RQLQ scores were also all found to differ significantly between
      groups (P<0.001). The total of both the public health care and private out-of
      pocket costs of SAC in our study population ranged on average between pound
      sterling 64.61 for a pensioner to pound sterling 123.69 for a person with SAC in
      paid employment. CONCLUSIONS: SAC is a costly, highly prevalent, chronic
      condition associated with significant reductions in both ocular and general
      quality of life, as well as ongoing out-of-pocket expenses and health care costs.
      Medications that reduce this demand on health care systems and out-of-pocket
      expenses by patients could be of potential importance in reducing the overall
      economic and health burden of illness posed by SAC.

PMID- 14977495
TI  - Daily cost of ophthalmic solutions used to treat allergic conjunctivitis in
      Japan.
AB  - PURPOSE: To estimate the daily cost of various ophthalmic solutions used in Japan
      for treating allergic conjunctivitis, including nine anti-allergic drugs and six
      anti-inflammatory drugs. METHODS: The drops contained in one bottle of each
      solution were counted. The cost per drop was calculated by dividing the
      government-controlled standard prices by the total number of drops in one bottle,
      and the daily cost of therapy was calculated by multiplying the cost per drop by
      the number of drops to be given per day. RESULTS: The total number of drops of
      the anti-allergic drugs in a bottle ranged from 108 to 169 and that of the anti
      inflammatory drugs from 100 to 145. The information in the package insert for
      these solutions recommends application 2-4 times daily. The price of the
      antiallergic drugs studied ranged from $6.35 to $8.38 and that of the anti
      inflammatory drugs studied from $2.02 to $5.20. The daily cost of the anti
      allergic drugs studied varied considerably, from $0.26 to $0.57; for the anti
      inflammatory drugs the range was from $0.12 to $0.20. Variations in the total
      number of drops per bottle and in the recommended dosage affect the daily cost of
      ophthalmic solutions. CONCLUSIONS: At current prices, the volume of a drop and
      the dosage had a greater effect on the daily cost than the price of a bottle.
      Daily cost data may be helpful in selecting ophthalmic products for treating
      allergic conjunctivitis in settings where the prices of a given drug are
      relatively uniform.

PMID- 14977496
TI  - TTO utility scores measure quality of life in patients with visual morbidity due
      to diabetic retinopathy or ARMD.
AB  - PURPOSE: To evaluate the utility scores in patients with varying degrees of
      visual morbidity due to diabetic retinopathy or ARMD. METHODS: Patients with
      vision < or =20/40 in one eye due to diabetic retinopathy or ARMD were enrolled.
      Utility scores were measured by the time trade-off (TTO) method after stratifying
      the patient population with visual impairment in the better eye (group 1, 20/20
      to 20/40; group 2, 20/50 to 20/100; group 3, 20/200 to no light perception).
      RESULTS: Sub-group analysis revealed that subjects in group 1 were willing to
      give up a median of 1 year as compared to 3 years by the subjects in group 3 for
      perfect bilateral visual acuity (P<0.05). The median utility score was 0.94 for
      group 1, 0.96 for group 2 and 0.80 for group 3. While the utility scores for
      groups 1 and 2 were comparable (P>0.05), there was a significant difference in
      the utility scores between groups 1 and 3 and between groups 2 and 3 (P<0.05).
      There was no significant effect on the utility scores of age, educational level
      or prior ocular surgery. CONCLUSION: Substantial visual loss secondary to
      diabetic retinopathy or ARMD is associated with a significant decrease in utility
      scores. However, TTO scores were not sensitive enough to demonstrate a difference
      between subjects with mild (group 1) and moderate (group 2) visual loss in the
      better eye secondary to diabetic retinopathy or ARMD.

PMID- 14977497
TI  - Moderate alcoholic beverage intake and early nuclear and cortical lens opacities.
AB  - PURPOSE: To study the relationship between alcoholic beverage intake and early
      lens opacities. METHODS: 556 Boston-area women aged 53-74 years were sampled from
      the Nurses' Health Study cohort. Degree of opacity was assessed by eye
      examinations including lens photography. RESULTS: After multivariate adjustment,
      the odds of a nuclear opacity grade > or =2.3 increased by 30% (OR=1.3, 95% CI:
      1.10-1.54) per 10-g increase in total alcohol intake. Furthermore, after control
      for intake of other alcoholic beverages, the odds of a higher nuclear opacity
      grade increased by 13% (OR=1.13, 95% CI: 1.02-1.26) for every two additional hard
      alcoholic drinks consumed per week, and by 17% (OR=1.17, 95% CI: 1.03-1.33) for
      every two additional glasses of wine consumed per week. The odds of a cortical
      opacity grade > or =0.4 decreased by 12% (OR=0.88, 95% CI: 0.79-0.98) for every
      two additional glasses of wine consumed per week, but intake of other alcoholic
      beverages was unrelated to cortical opacity. CONCLUSIONS: Consumption of
      alcoholic beverages, particularly hard liquor and wine, was positively related to
      nuclear opacity. Wine drinking was inversely related to cortical opacity.

PMID- 14977499
TI  - Challenges for surveillance for injury prevention.
AB  - Injury surveillance has, and will continue to have, a critical role to play in
      reducing injury. If injury surveillance is going to realise its full potential in
      reducing injury, however, there are a number of challenges we need to address.
      These include: (1) agreeing on what is an injury, (2) focusing on important
      injuries, (3) improving surveillance of important injury events, and (4)
      improving surveillance of risk and protective factors.

PMID- 14977500
TI  - Rapid assessment procedures in injury control.
AB  - Injuries are among the leading causes of death and disability worldwide. The
      burden caused by injuries is even greater among the poorer nations and is
      projected to increase. Very often the lack of technical and financial resources,
      as well as the urgency of the problem, preclude applying sophisticated
      surveillance and research methods for generating relevant information to develop
      effective interventions. In these settings, it is necessary to consider more
      rapid and less costly methods in applying the public health approach to the
      problem of injury prevention and control. Rapid Assessment Procedures (RAP),
      developed within the fields of epidemiology, anthropology and health
      administration, can provide valid information in a manner that is quicker,
      simpler, and less costly than standard data collection methods. RAP have been
      applied widely and successfully to infectious and chronic disease issues, but
      have not been used extensively, if at all, as tools in injury control. This paper
      describes Rapid Assessment Procedures that (1) are useful for understanding the
      scope of the problem and for identifying potential risk factors, (2) can assist
      practitioners in determining intervention priorities, (3) can provide in-depth
      knowledge about a specific injury-related problem, and (4) can be used in
      surveillance systems to monitor outcomes. Finally, the paper describes some of
      the caveats in using RAP.

PMID- 14977501
TI  - The role of supervision in child injury risk: definition, conceptual and
      measurement issues.
AB  - The purpose of this paper was to examine caregiver supervision and its role as an
      active strategy in childhood injury prevention. Through a review of the
      literature, the authors addressed conceptual and methodological issues related to
      supervision, such as the question of how to define 'adequate supervision.' Three
      critical dimensions (attention, proximity and continuity) of caregiver
      supervisory behaviors are identified as important areas for measurement.
      Presented is a framework for understanding the role of passive and active
      supervisory behaviors within the social context. The framework includes family
      and community characteristics and policies/regulations that may be important in
      caregiver decisions to use active or passive injury prevention strategies. Future
      research directions are discussed.

PMID- 14977502
TI  - Matched analysis of parent's and children's attitudes and practices towards motor
      vehicle and bicycle safety: an important information gap.
AB  - The purpose of this study was to compare parents' and children's attitudes and
      habits towards use of bicycle helmets and car seat belts. We hypothesized that
      parental perception of their children's safety practices did not reflect actual
      behavior and further, that parental practices, rather than their beliefs about a
      particular safety practice, have a greater affect on their child's risk-taking
      behavior. The study population consisted of children in grades four and five and
      their parents/guardians. Participation in the cross-sectional study was voluntary
      and confidential anonymous questionnaires were used. In separate and independent
      surveys, children and parents were questioned in parallel about their knowledge,
      habits and attitudes toward bicycle helmet use and car safety practices. In the
      study, 731 students participated with 329 matched child-parent pairs. Ninety-five
      percent of the children own bicycles and 88% have helmets. Seventy percent of
      parents report their child always wears a helmet, while only 51% of children
      report always wearing one (p < 0.05). One-fifth of the children never wear a
      helmet, whereas parents think only 4% of their children never use one (p < 0.05).
      Parents report their children wear seat belts 92% of the time while 30% of
      children report not wearing one. Thirty-eight percent of children ride bicycles
      with their parents and wear their helmets more often than those who do not ride
      with their parents (p < 0.05). Parents who always wear a seat belt are more
      likely to have children who sit in the back seat and wear a seat belt (p < 0.05).
      Parents' perceptions of their children's safety practices may not be accurate and
      their actions do affect their children's. Injury prevention programs that target
      both parents and children may have a greater impact on reducing risk-taking
      behaviors than working with each group in isolation.

PMID- 14977503
TI  - Determinants of work injuries in mines - an application of structural equation
      modelling.
AB  - In spite of stringent regulations and much attention towards reducing risks in
      the physical environment, the mining industry continues to be associated with
      high levels of accidents, injuries and illnesses. Only engineering solutions to
      accident prevention are inappropriate unless coupled with focused attention to
      the attitudes and behaviours of the mineworkers in coping with the inherent
      physical, technical and situational risks. The present study identified these
      various risk factors and analysed their influences on work injury in a causal
      framework. Data were collected from an underground coalmine of India. The pattern
      and strength of relationships of 16 causal factors with work injuries were
      assessed through structural equation modelling. The case study results showed
      that negatively personified individuals are of major concern for safety
      improvement in the mine studied. They not only fail to avoid work injuries, they
      are unable to extend safe work behaviours in their work. The variable safety
      environment is negatively affected by personality, whereas social support has a
      positive relationship with safety environment. The variable job hazards appeared
      to have a significant relationship with job involvement, which has a negative
      relationship with work injury. Elimination of negative behaviours must be focused
      and committed by the mine safety management. Long term planning through (i)
      identification of negative individuals, (ii) proper councelling of adverse
      effects of negative behaviours, and (iii) special training with psychological
      treatment is highly required. Identification may begin while recruiting new
      workers through interview. Proper allocation of jobs (right person for right job)
      may be a judicial solution to this end.

PMID- 14977504
TI  - A local bicycle helmet 'law' in a Swedish municipality - the effects on helmet
      use.
AB  - The municipality of Motala in Sweden introduced a local bicycle helmet 'law' on
      May 1, 1996. This is not a legally enacted ordinance, but instead a legislated
      recommendation backed up by information and education. Formally, the law applies
      to children (aged 6-12 years), although the intention is to increase helmet use
      by all cyclists. The objective of the present study was to quantitatively
      evaluate the impact of the Motala helmet law on observed use of helmets by
      children and adults. Bicycle helmet use was monitored in Motala (n = 2,458/year)
      and in control towns (n = 17,818/year) both before and after adoption of the
      helmet law (1995-1998). Chi-square tests showed that helmet wearing 1995-1998
      increased in Motala among all bicyclists (from 6.1% to 10.5%) and adults biking
      on cycle paths (from 1.8% to 7.6%). Helmet use by school children aged 6-12
      increased during the first 6 months after introduction of the law (from 65.0% to
      75.7%) but then progressively decreased to the pre-law level. Considering
      children cycling on cycle paths and for recreation in housing areas, there was a
      tendency towards increased helmet use during the first post-law year, but this
      was followed by a reduction to a lower level in 1998 than in 1995. Logistic
      regression analysis taking into account data from the control towns indicated
      that the helmet law had a positive effect on children cycling to schools during
      the first 6 months, and a weak delayed but more long-term positive effect on
      adult cyclists on cycle paths. There were no positive effects on children in
      housing areas and on cycle paths. The Motala helmet law probably would have had
      greater and more lasting effects on helmet use by bicyclists, if certain problems
      had been avoided during the initiation phase. Moreover, although it did have a
      positive influence on both school children and adults, it is not legally binding,
      and hence no penalties can be imposed. Presumably, compulsory legislation would
      have a more substantial impact on helmet wearing than a non-mandatory helmet
      'law' such as that introduced in Motala.

PMID- 14977505
TI  - Knowledge, beliefs and attitudes of squash venue operators relating to use of
      protective eyewear.
AB  - Sports venues are in a position to potentially influence the safety practices of
      their patrons. This study examined the knowledge, beliefs and attitudes of venue
      operators that could influence the use of protective eyewear by squash players. A
      50% random sample of all private and public squash venues affiliated with the
      Victorian Squash Federation in metropolitan Melbourne was selected. Face-to-face
      interviews were conducted with 15 squash venue operators during August 2001.
      Interviews were transcribed and content and thematic analyses were performed. The
      content of the interviews covered five topics: (1) overall injury risk
      perception, (2) eye injury occurrence, (3) knowledge, behaviors, attitudes and
      beliefs associated with protective eyewear, (4) compulsory protective eyewear and
      (5) availability of protective eyewear at venues. Venue operators were mainly
      concerned with the severe nature of eye injuries, rather than the relatively low
      incidence of these injuries. Some venue operators believed that players should
      wear any eyewear, rather than none at all, and believed that more players should
      use protective eyewear. Generally, they did not believe that players with higher
      levels of experience and expertise needed to wear protective eyewear when
      playing. Only six venues had at least one type of eyewear available for players
      to hire or borrow or to purchase. Operators expressed a desire to be informed
      about correct protective eyewear. Appropriate protective eyewear is not readily
      available at squash venues. Better-informed venue operators may be more likely to
      provide suitable protective eyewear.

PMID- 14977506
TI  - A benefit-cost analysis of the Harlem hospital injury prevention program.

PMID- 14977507
TI  - Cost analysis of road traffic crashes in South Africa.

PMID- 14977508
TI  - Injury minimization in construction projects.

PMID- 14977509
TI  - Clubs volunteering for sports injury prevention research - is there any selection
      bias?

PMID- 14977511
TI  - How well do measures of inhibition and other executive functions discriminate
      between children with ADHD and controls?
AB  - The aim of the present study was to evaluate the usefulness of Barkley's (1997a)
      model of inhibition and executive functioning in describing the deficits
      associated with Attention Deficit Hyperactivity Disorder (ADHD). Besides group
      differences, the present study addressed the question of independent effects of
      inhibition and the other executive functions in discriminating between children
      with ADHD and controls and how well, in terms of sensitivity and specificity,
      these measures can classify the children into the correct group. The results
      showed that children with ADHD differed significantly from controls with regard
      to measures of inhibition as well as all other executive function measures,
      except repetition of hand movements. In logistic regression models, three
      different measures tapping inhibition, working memory and emotion regulation were
      shown to be significant independent predictors of group membership. The
      sensitivity for these three variables as a set was 76.2, the specificity was
      90.5, with a total of 86% of the sample correctly classified. When excluding the
      parental rating of emotion regulation, the overall classification rate decreased
      some, but was still relatively high in comparison with previous studies within
      this area of research.

PMID- 14977512
TI  - Math weaknesses in survivors of acute lymphoblastic leukemia compared to healthy
      children.
AB  - Difficulties in math are the most frequently reported area of academic deficit in
      survivors of acute lymphoblastic leukemia (ALL) and the most frequent academic
      complaint among parents of ALL survivors. However, previous studies that included
      measures of math skills have been limited by the use of only a single measure of
      math skills, most often a measure of written calculations, without any assessment
      of math reasoning or math application skills. Further, the nature of these math
      difficulties has not been adequately investigated. The purpose of this study was
      to examine the performance of ALL survivors using multiple measures of math
      skills. Performance was compared to a group of healthy controls matched for age
      and sex as well as to normative levels. Other measures of neuropsychological
      function were also administered, and the relationships between these measures and
      the math measures were explored. Converging evidence for math difficulties in ALL
      survivors compared to healthy controls and normative levels was found. While ALL
      survivors generally performed within the average range on measures of math
      skills, math performance was mostly related to memory function and dominant-hand
      psychomotor speed. By contrast, math performance of healthy children was mostly
      related to basic reading skills and visual-motor integration. These findings shed
      light on the nature of math difficulties in ALL survivors and have implications
      for intervention.

PMID- 14977513
TI  - Early neuropsychological correlates of later clock drawing and clock copying
      abilities among school aged children.
AB  - Although widely used in empirical study and bedside neuropsychological evaluation
      of geriatric populations, there is little literature on clock copying and drawing
      among children. However, existing research suggests that clock drawing tests
      (CDTs) may be effective and efficient tools for assessing neurocognitive
      development in children. This paper reports data on clock drawing on demand (CDT
      D) and clock drawing to copy (CDT-C) among a non-clinical sample of elementary
      school aged children and identifies predictive relationships between earlier
      measures of executive function, visuo-construction, and visual-motor coordination
      and CDT performance 3 years later. Similar to findings with adult samples,
      analyses revealed better performance on copying than on drawing. Longitudinal
      analyses indicate that general intelligence significantly predicted performance
      on both tasks. Visual-motor coordination only predicted performance on the
      drawing on demand subtest of the CDT.

PMID- 14977514
TI  - Neurocognitive correlates of type 1 diabetes mellitus in childhood.
AB  - Type 1 Diabetes Mellitus (T1DM) is one of the most prevalent chronic health
      conditions in children under the age of 18 years. Complications of the disease
      include hypo- and hyperglycemia, which can have an impact on children's
      performance in assessment situations, in the clinic, and in school. Because there
      is no cure for this disease, there is a need to understand the cognitive deficits
      associated with some of its complications, as this knowledge will impact on the
      choice of treatment regimens as well as educational interventions. This paper
      provides a comprehensive review of the relevant literature on the neurocognitive
      outcome of T1DM. In particular, disease- and treatment-related variables that are
      associated with poor performance on cognitive domains will be reviewed.
      Specifically, age of onset, duration, pubertal effects, and presence of
      hypoglycemia or hyperglycemia will be examined. These findings are not without
      controversy, and limitations to conclusions will also be presented. Where
      relevant, recommendations for future research directions will be provided.

PMID- 14977516
TI  - The Ginkgo biloba extract (EGb 761) provides a neuroprotective effect on retinal
      ganglion cells in a rat model of chronic glaucoma.
AB  - PURPOSE: To investigate the effect of Ginkgo biloba extract (EGb 761) against
      neurotoxicity of retinal ganglion cells of rats with chronic moderately elevated
      intraocular pressure (IOP). METHODS: Unilateral chronic moderately elevated IOP
      was produced in rats by cautery of three episcleral vessels. Secondary
      degeneration was measured with and without EGb 761 for 5 months. At 5 months,
      retinal ganglion cells were labeled with a fast blue tracer applied to both
      superior colliculi. Densities of surviving retinal ganglion cells were estimated
      by counting fast blue labeled cells in whole mounted retinas. RESULTS: When
      compared with their contralateral control eyes with normal IOP, in the peripheral
      retina, retinal ganglion cell loss in eyes with chronic, moderately elevated IOP
      was 29.8 +/- 1.5% (n=5) at 5 months in untreated animals and 4.6 +/- 4.5% (n=5)
      at 5 months in treated animals with EGb 761. CONCLUSIONS: Pretreatment and early
      posttreatment with EGb 761 is an effective neuroprotectant in a rat model of
      chronic glaucoma.

PMID- 14977517
TI  - Expression of glutamate transporter subtypes in cultured retinal pigment
      epithelial and retinoblastoma cells.
AB  - PURPOSE: Glutamate is the major excitatory neurotransmitter in the retina and
      glutamate uptake is essential for normal glutamate signalling. Retinal diseases
      may induce neurochemical changes which affect retinal cells including retinal
      pigment epithelium (RPE). The aim of the study was to investigate the expression
      of glutamate transporter subtypes in RPE and retinoblastoma cells and to clarify
      the effect of proliferation modulators on the levels of the expressed transporter
      in the RPE cell line. METHODS: Cultured pig RPE cells and two human RPE cell
      lines, D407 and ARPE-19, as well as the human retinoblastoma cell line Y79 were
      used. Glutamate transporter expression was evaluated with Western blot analysis
      and immunocytochemistry. RESULTS: The study revealed unexpected expression of
      neuronal glutamate transporter/chloride channel EAAT4 in these three cell lines,
      but not in cultured pig RPE cells, whereas another glutamate carrier, EAAC1, was
      present in all cell types utilized. Other transporter subtypes, GLT1, GLAST and
      EAAT5 were not found. Neither tamoxifen, known to inhibit both proliferation and
      glutamate uptake in RPE cells, nor retinoic acid nor insulin, also known to
      affect cell proliferation rates, were capable of changing the total levels of
      EAAT4 in APRE-19 cells. CONCLUSIONS: Neuronal glutamate transporter EAAC1 is
      expressed in RPE cells. The robust expression of EAAT4 in cell lines may reflect
      a role of EAAT4 in cell proliferation and migration. Unaltered steady-state
      expression of this carrier and chloride-channel protein hints at
      posttranslational mechanisms of regulation of EAAT4.

PMID- 14977518
TI  - Vasodilatory mechanism of unoprostone isopropyl on isolated rabbit ciliary
      artery.
AB  - PURPOSE: To clarify the vasodilatory mechanism of unoprostone isopropyl
      (unoprostone), a PG F2alpha related compound used for treatment of glaucoma, we
      have investigated the effect of this drug and its metabolites on isolated rabbit
      ciliary artery in vitro. METHODS: Under the dissecting microscope, ciliary
      arteries were prepared from albino rabbit eyes and mounted in a myograph system.
      The effects of unoprostone isopropyl and other agents were investigated using
      isometric tension recording methods. RESULTS: Unoprostone induced a dose
      dependent relaxation in ciliary arteries that were pre-contracted with high-K
      solution, 10 microM histamine or 10 microM PG F2alpha. Neither unoprostone
      metabolite M1 or M2 had a relaxant effect on the precontracted vessels.
      Relaxation was unaffected by inhibition of adenylyl cyclase with SQ 22536,
      guanylyl cyclase with ODQ, or maxi-K channels with iberiotoxin. Pretreatment with
      unoprostone did not affect histamine-induced transient contractions in Ca2+ -free
      solution. However, SKF96365, a general Ca2+ channel blocker, evoked relaxation
      similar to unoprostone with respect to amplitude and rate of onset. CONCLUSIONS:
      Unoprostone, but not its metabolites M1 and M2, relaxed pre-contracted rabbit
      ciliary artery. The mechanism of vascular smooth muscle relaxation by unoprostone
      differs from that of IOP reduction and does not depend on adenylyl cyclase,
      guanylyl cyclase, or maxi-K channels. Relaxation may be mediated by inhibition of
      Ca2+ entry, possibly through capacitative Ca2+ channels.

PMID- 14977519
TI  - Age of lens use onset in a myopic sample of office-workers.
AB  - PURPOSE: The present study was developed to assess prevalence of myopic
      refractive error and the relative percentages of youth- and adult- onset myopia
      in a Caucasian adult population. METHODS: Subjects were office-workers sent
      consecutively from their workplace for a general health check-up, without
      refractive selection. Each subject received a questionnaire about academic
      achievement and family history of myopia. Subsequently, an ophthalmologist
      performed the vision examination. Although age of initial lens use is not
      necessarily the same as age of onset of myopia, it was considered to be so for
      this paper. A subject was considered an adult-onset myope if lens use began at
      age 18 or later. RESULTS: Subjects (n=349) had a mean age of 37.6 +/- 9.3 years.
      One hundred seventeen subjects (33.5% prevalence) had myopic spherical equivalent
      refraction. Further analysis comprises only subjects with simple myopia
      (astigmatism <1 diopter, n=95). Nearly half of the simple myopic subjects were of
      adult-onset (47.8%). There was no difference in family history of myopia between
      youth- and adult-onset myopes (at least one myopic parent in 53.1% and 47.8%
      respectively, p=0.53), and no clear cut-off point separated the two myopic
      subgroups with respect to the age of lens use onset. However, adult-onset myopes
      had myopia of lower diopter amount than youth-onset myopes. CONCLUSIONS: Adult
      onset myopes comprised nearly half of the simple myopic subjects, and their
      family history of myopia was similar to that of youth-onset myopes. There is no
      clear cut-off point between both myopic subgroups when age of onset is the
      variable considered.

PMID- 14977520
TI  - Effect of human RAD50 gene therapy on glaucoma filtering surgery in rabbit eye.
AB  - PURPOSE: To investigate the antiproliferative effects of the subconjunctival
      injection of human RAD50 (hRAD50) on fibroblasts after glaucoma filtering
      surgery. METHODS: After glaucoma filtering surgery in normal rabbit eye, the
      subconjunctival injection of hRAD50 was performed. Morphologic changes in the
      subconjunctival area of hRAD50-treated eyes were compared with those of mitomycin
      C (MMC)-treated and control eyes using light and electron microscopy. Results.
      Two weeks after hRAD50 treatment (2 microg), the conjunctival epithelium
      increased in thickness and had many tonofilaments, but the basal lamina was
      intact. The subconjunctival fibroblasts exhibited a granular endoplasmic
      reticulum without distension. Most of the collagen bundles and fibers around the
      fibroblasts disappeared, and apoptotic cells with many fragmented nuclei and
      condensed chromatin were observed. Four weeks after hRAD50 treatment, the
      findings were similar with those of 2 weeks except for a slight increase in the
      number of collagen bundles and fibers and the appearance of macrophages. In MMC
      treated eyes, the conjunctival epithelium also increased in thickness and had
      many tonofilaments. However, intercellular spaces were widened and the basal
      lamina was interrupted in some areas. Most of the collagen bundles and fibers
      were shortened, and apoptotic cells were also observed. CONCLUSIONS: These
      results demonstrate that the histologic antiproliferative effects of local hRAD50
      on the conjunctival fibroblasts are similar to those of MMC, but without damage
      to the basal lamina of the conjunctival epithelium, and suggest that hRAD50 may
      be useful as a possible antifibroblastic agent for glaucoma filtering surgery.
      However, further investigations are needed to test for possible systemic
      complications, which so far have not been reported.

PMID- 14977521
TI  - Ibopamine provocative test and glaucoma: consideration of factors that may
      influence the examination.
AB  - PURPOSE: To evaluate factors that may influence the ibopamine provocative test
      for the diagnosis of glaucoma. METHODS: Two Ibopamine (3,4 di-isobutyrylester of
      N-methyldopamine) 2% eyedrops were instilled 5 minutes apart in one eye selected
      at random in both glaucoma and normal subjects. The intraocular pressure (IOP)
      was assessed prior to the drops and 30, 60 and 180 minutes after instillation.
      The test was considered positive when there was an IOP increase of greater than 4
      mmHg at any one of the timepoints. The amount of IOP change was compared to the
      severity of glaucomatous visual field loss and to the types of medical treatment.
      RESULTS: The sensitivity (glaucoma patients with a positive result) and
      specificity (normal individuals with a negative result) of the Ibopamine test was
      87 and 95%, respectively. Glaucoma patients using prostaglandin analogues did not
      have a significant IOP elevation. CONCLUSION: The Ibopamine provocative test may
      be an auxiliary test in glaucoma diagnosis. Concurrent use of prostaglandin
      analogues reduces the test's sensitivity.

PMID- 14977522
TI  - Zn2+-induced cell death is mediated by the induction of intracellular ROS in ARPE
      19 cells.
AB  - PURPOSE: Recent studies have shown that Zn2+ induced cell death in retinal
      pigment epithelial cells. Here we sought to investigate the mode of Zn2+-induced
      cell death and the role of reactive oxygen species (ROS) in human retinal pigment
      epithelial cell line, ARPE-19 cells. METHODS: Cell viability was measured by MTT
      assay. Cell death of ARPE-19 cells was measured by annexin V-fluorescein
      isothiocyanate (FITC) binding assay, TUNEL assay. The formation of intracellular
      ROS was measured using 2',7'-dichlorofluorescein diacetate (DCFH-DA). The
      activation of mitogen-activated protein kinase (MAPK) was examined by Western
      blot analysis. RESULTS: This study demonstrated that Zn2+ treatment induced both
      necrosis and apoptosis in ARPE-19 cells. Exposure of ARPE-19 cells to Zn2+ led to
      the activation of ERK1/2, JNK1/2/3, and p38 MAPKs. The activation of these MAPKs
      was blocked by treatment with the antioxidant, N-acetylcystein (NAC). More
      importantly, inhibition of ROS production by NAC completely prevented Zn2+
      induced cell death in RPE cells. CONCLUSIONS: This study suggests that Zn2+
      induces both apoptosis and necrosis in ARPE-19 cells and that its cytotoxicity
      may depend on the induction of intracellular ROS.

PMID- 14977523
TI  - Further assessment of the size, shape and surface features of superficial cells
      of the bovine corneal epithelium, using scanning electron microscopy.
AB  - PURPOSE: To qualitatively and quantitatively assess the size and shape of the
      surface cells of the bovine corneal epithelium as assessed by scanning electron
      microscopy. METHODS: After quality-control measures on recent postmortem bovine
      eyes obtained from a slaughterhouse, the ocular surface was aggressively washed
      with 0.97% saline and then fixed for scanning electron microscopy (SEM) by a
      dropwise application, in 37 degrees C moist chamber, of a 2% glutaraldehyde
      solution (in 80 mM cacodylate, pH 7.2 to 7.4). A set of images were taken from
      the central region of the surface of the corneal epithelium. The cell areas,
      perimeter and dimensions of 25 to 30 cells from 18 different samples were
      measured with a digitiser pad or rule, and number of bordering cells (sides)
      counted manually. Cell shape was assessed by comparing the longer and shorter
      dimensions (LS ratio) and calculation of the figure coefficient (FC, 4PiA/P2 ).
      RESULTS: With the washing protocol, surface cells were evident that displayed a
      range of electron reflexes (light, medium and dark) and that were decorated with
      microplicae and some crater-like features. These features were generally not
      evident if the surface was only rinsed with saline. The cell surface areas ranged
      from 58 to 6444 microm2 (mean 1748 +/- 1169 microm2), and increased as the number
      of sides increases. Cells with a higher number of sides (n=10) tended to be more
      rounded (LS ratio averaging 1.24) while cells with small number of sides (n=3)
      were more elongated (LS ratio 1.94). Shape (FC) values ranged from 0.379 to
      0.967, and increased as the number of cell sides increases. Assessment of cell
      shape in relation to the number of cell sides identified only a small proportion
      of surface cells with unusually low FC values. CONCLUSIONS: With an appropriate
      preparative procedure (aggressive washing with saline), bovine corneal epithelial
      surface (squamous) cells can be shown to have a similar appearance by SEM to that
      previously observed for rabbit and human corneas. The cell sizes are however
      substantially greater than those seen in rabbits, presumably because of the much
      larger corneal diameter (c. 28 mm vs. 13 mm). Based on detailed analysis of cell
      size and shape, the results indicate that the squamous cells have reasonably
      predictable characteristics.

PMID- 14977524
TI  - Contrary effects of cytokines on mRNAs of cell cycle- and ECM-related proteins in
      hRPE cells in vitro.
AB  - PURPOSE: Retinal pigment epithelial (RPE) cells play a pivotal role in the
      pathogenesis of proliferative vitreoretinopathy (PVR). As a result of a breakdown
      of the blood-retina barrier, growth factors obtain access to the subretinal space
      and stimulate several retinal cell types. The aim of the present study was to
      analyze the effect of several growth factors on the proliferation of human (h)RPE
      cells, and on the mRNA expression of transcription factors, cell cycle proteins,
      and extracellular matrix (ECM) proteins. METHODS: hRPE cells were incubated in
      the presence of TGF-beta1, TGF-beta2, PDGF, VEGF, or bFGF for 24-72 h. Cell
      proliferation was assessed by determinating BrdU incorporation. Changes in mRNA
      expression of c-fos, c-myc, PCNA, FEN1, Ki67, collagen III, and collagen IV were
      investigated by ribonuclease protection assay (RPA). RESULTS: RPE cell
      proliferation was significantly increased by exposure to PDGF and bFGF for 48 h,
      and was decreased by application of TGF-beta1 and TGF-beta2 for 48 and 72 h. All
      the tested growth factors significantly elevated the amounts of c-fos mRNA (after
      1 h) and of c-myc mRNA (after 24 h). PDGF and bFGF up-regulated the expression of
      Ki67 mRNA, and down-regulated that of collagen III and collagen IV mRNA after 24
      h. TGF-beta1 and TGF-beta2 decreased the expression of Ki67 mRNA, and increased
      that of collagen III and collagen IV mRNA. CONCLUSION: Our results show that
      distinct cytokines may induce contrary effects with respect to proliferation of,
      and ECM formation by, hRPE cells in vitro. This knowledge may be useful for the
      development of improved therapeutic approaches.

PMID- 14977525
TI  - Frizzled/WNT signalling: the insidious promoter of tumour growth and progression.
AB  - The recognition that the processes involved in tumour formation are strikingly
      similar to developmental morphogenetic processes, such as gastrulation, has
      refashioned our approach to cancer research. Wnt and its receptor Frizzled govern
      the morphogenetic processes of gastrulation. Directed cell movements during
      gastrulation require the cells to undergo transient epithelial to mesenchymal
      transitions, enabling the cells to dissociate and migrate. To do this, Frizzleds
      activate different intracellular signalling cascades that affect cellular
      processes such as differentiation, proliferation, cell motility and cell
      polarity. Cell dissociation and migration are also essential for tumour cell
      invasion and metastases and the frequent deregulation of Wnt and Frizzled in
      human cancers implicates them in this process. Indeed recent evidence links both
      canonical (Wnt/beta-catenin) and non-canonical (Wnt/Ca2+) pathways to tumour
      invasion and metastases, emphasizing the importance of Frizzled in tumour growth
      and progression.

PMID- 14977526
TI  - Mn2+ and bacterial pathogenesis.
AB  - Fe2+ has traditionally been considered the most important divalent cation
      involved in host-pathogen interactions. However, recent research indicates a
      previously unappreciated role for transition metal divalent cations other than
      Fe2+ during infection. Recent studies have identified an absolute requirement for
      Mn2+ in bacterial pathogens that are Fe2+-independent, indicating an important
      role for Mn2+ in pathogenesis. Potential roles for Mn2+ in pathogenesis include
      effects on the detoxification of reactive oxygen intermediates (ROIs), as a
      cofactor for enzymes involved in intermediary metabolism and signal transduction,
      and as a stimulus for virulence gene regulation. This review focuses on how these
      possible roles for Mn2+ may affect bacterial pathogenesis and the outcome of an
      infection.

PMID- 14977527
TI  - WNT-frizzled signaling via cyclic GMP.
AB  - Wnt-Frizzled signaling is an essential aspect of early development, regulating
      cell fate, polarity, differentiation, and migration. In addition to the well
      known Wnt/beta-catenin pathway characterized for Frizzled-1, there are other
      pathways regulated by Wnts that are not mediated by Frizzled-1 and do not lead to
      stabilization of beta-catenin and activation of the Lef/Tcf-sensitive
      transcription of genes. The first of these non-canonical pathways to be
      identified is the Wnt/Ca++ pathway in which Frizzled-2 activation leads to
      release of beta/gamma subunit complexes from heterotrimeric G-proteins
      (presumably Go and Gt) to activate phospholipase C and other effectors to
      stimulate a mobilization of intracellular Ca++. More recently a second, related
      pathway of Wnt-Frizzled signaling has been discovered that regulates the
      intracellular levels of cyclic GMP. Frizzled-2, established as a member of the
      family of 7TMS receptors that couple by heterotrimeric G-proteins to effectors,
      can signal via the G-protein Gt2, transducin, a G-protein prominent in
      phototransduction in the eye, to cyclic GMP phosphodiesterase. The discovery of
      the expression of Gt2 in embryonic cells was co-incident with the demonstration
      that inhibitors of cyclic GMP phosphodiesterase potently blocked various features
      of Frizzled-2 signaling in mouse embryonic F9 cells and in zebrafish embryos. The
      signal linkage map from Wnt to changes in intracellular cyclic GMP and
      development is the focus of this review. The molecular features of how changes in
      intracellular cyclic GMP concentrations control development remain to be
      elucidated.

PMID- 14977528
TI  - Frizzleds: new members of the superfamily of G-protein-coupled receptors.
AB  - The superfamily of membrane receptors that signal via heterotrimeric G-proteins
      includes more than 1500 members, classified into five basic groups, representing
      about 5-10% of the human genome. These G-protein-coupled receptors operate
      through a comparatively smaller group of heterotrimeric G-protein family of
      approximately 20 members, each displaying an alpha subunit that binds and
      hydrolyzes GTP in combination with the beta-/gamma-subunit complex that is
      largely non-dissociable in vivo. Frizzleds represent the cell membrane receptors
      for a family of secreted glycoprotein ligands termed "Wnts" that play essential
      roles in development, including cell fate, adhesion, polarity, migration, and
      proliferation. Based upon a compelling set of experimental observations about the
      structure and downstream signaling of Wnt-Frizzled signaling, one can only
      conclude that Frizzleds are true members of the GPCR family and require
      heterotrimeric G-proteins to propagate signals from the Wnts to well-known
      effectors, including beta-catenin stabilization, mobilization of intracellular
      Ca2+, and activation of cyclic GMP phosphodiesterase. Careful study of primary
      structure of Frizzleds reveal heptihelical, 7-transmembrane segments,
      characteristic of GPCRs. Chimeric forms of Frizzleds, making use of the
      cytoplasmic domains of Frizzleds, substituted into the exofacial and
      transmembrane segments of the prototypic GPCR beta2-adrenergic receptor are
      functional and display the well-known GTP-shift in receptor affinity. Suppression
      of specific G-protein subunits suppress the ability of chimeric as well as
      authentic Frizzled-1 and Frizzled-2 to signal to their canonical pathways upon
      activation. The involvement of beta-arrestin, an important regulator of GPCR
      signaling, in Frizzled signaling is, therefore, not unexpected. Recognition of
      the GPCR character of Frizzled enables a more broad understanding of these
      receptors and of their mechanisms of downstream signaling.

PMID- 14977529
TI  - The search for new sterilizing anti-tuberculosis drugs.
AB  - To be of use in the control of tuberculosis, any new drug must be capable of
      shortening the duration of treatment by accelerating sterilizing activity, that
      is the rate at which Mycobacterium tuberculosis is killed in the lesions. The
      most difficult to kill are the extra-cellular bacilli in cavities. Persistence
      during therapy arises because there is a proportion of slowly metabolising
      bacilli (persisters) in the cavitary bacterial population at the start of
      treatment. Bacterial growth is slowed by low oxygen tension, quorum sensing and
      old age, but probably not by cellular immunity, since there are few professional
      phagocytic cells in cavities. The degree of phenotypic resistance to the
      bactericidal action of drugs can go through several stages: (i) the non
      replicating stages 1 and 2 of micro-aerophilic adaptation, described by Wayne;
      (ii) a "tolerant" population that survives exposure to high rifampicin
      concentrations and is capable of growth in liquid medium but not on solid medium;
      and (iii) a population found in the sterile state of Cornell model mice which
      cannot grow initially in either liquid or solid medium but will eventually cause
      re-activation of tuberculosis. In all of these stages the bacilli are
      phenotypically resistant; there is no selection for genomic drug resistance.
      Rifampicin and pyrazinamide are the two drugs largely responsible for sterilizing
      activity during current treatment. Pyrazinamide is unique amongst anti
      tuberculosis drugs in having no genomic site of action and having greater
      bactericidal activity as bacillary metabolism slows down; it is remarkably
      effective in human disease. The development of a new drug with a similar mode of
      activity might be very fruitful, especially if there were no need for an acid
      environment. Current methods advocated for drug development pass through a number
      of complex stages: choice of a genomic target, development of an in vitro assay,
      high throughput screening and identification of lead compounds, often with
      scaling up of synthesis of the molecule and preliminary studies of toxicity and
      animal pharmacology before tests are done for sterilizing activity. If the drug
      is not good at sterilizing, all of this initial work will be largely wasted as it
      would only have a very limited role in the treatment of MDR disease. One of the
      most important steps necessary is the development of rapid and simple tests to
      screen for sterilizing activity. Of tests currently available, none of those
      employing mice seem adequate, though a screen using a streptomycin dependent
      Mycobacterium tuberculosis seems the most hopeful. A set of in vitro tests is
      described. There is an urgent need to develop these tests further since the
      factors slowing growth are closer to those in tuberculous cavities than in mouse
      models. They have the advantages of simplicity and require only small amounts of
      a new molecule.

PMID- 14977530
TI  - Elevated expression of IFN-gamma in the HIV-1 infected brain.
AB  - We determined the extent of expression of three cytokines (IFN-gamma, IL-4, and
      TNF-alpha ) in brain tissue infected with human immunodeficiency virus-1 (HIV-1).
      The selections were IFN-gamma as a Th1 cytokine, IL- 4 as a Th2 cytokine, and TNF
      alpha as a pro-inflammatory cytokine (and because of its prior implication in
      brain tissue damage due to HIV-1 infection). Based on current models for
      pathogenesis of HIV-1-associated dementia (HAD), in the periphery, Th1 cytokines
      are considered to be salutary, whereas Th2 cytokines are regarded as deleterious.
      However, we hypothesized that in the CNS these roles are reversed. Post-mortem
      temporal lobe tissue specimens from 16 HIV-1-seropositive patients and 11 HIV-1
      seronegative controls were stained for IFN-gamma, IL-4, and TNF-alpha utilizing
      immunohistochemistry and alkaline phosphatase. HIV-1 infection causes alterations
      of brain cytokine expression that include increased IFN-gamma expression for HIV
      1-seropositive vs. HIV-1-seronegative individuals. There was increased expression
      of IFN-gamma for HIV-1-seropositive individuals with or without HAD, with or
      without the broader category of neuropsychiatric impairment (NPI), and with or
      without opportunistic infections (OIs) compared to HIV-1-seronegatives. A
      significant inverse correlation between IFN-gamma vs. IL-4 in HIV-1-seropositives
      with HAD and in seronegative individuals was observed. There was an inverse
      correlation in seropositives between IFN-gamma vs. TNF-alpha, a positive trend
      with HAD, significant without HAD, significant with NPI and significant without
      OIs. Between IL-4 vs. TNF-alpha there was a correlation (trend) in seropositives,
      a trend with NPI, significant without NPI, and a trend without OI. Due to HIV-1
      infection of the brain and neurological disease there is a prominent increased
      expression of IFN-gamma, an inverse expression of IFN-gamma vs. TNF-alpha, and
      TNF-alpha vs. IL-4. The inverse correlation between increased IFN-gamma and
      decreased IL-4 expression is consistent with the stimulation of activated
      macrophages, and T cells, greater toxicity in the HIV-1-infected brain, and is
      supportive of the significance of IFN-gamma in HIV-1-infected patients.

PMID- 14977531
TI  - Macroscopic electrostatic models for protonation states in proteins.
AB  - The use of macroscopic electrostatic models to calculate the relative energetics
      of protonation states and the pH-titration properties of ionizable groups in
      proteins is described. These methods treat the protein as an irregularly-shaped
      low-dielectric object containing embedded atomic charges immersed in a high
      dielectric (solvent) medium. The energetics of altering protonation states then
      involves the electrostatic work of altering the embedded atomic charges. The
      governing electrostatic equation is either the Poisson or linearized Poisson
      Boltzmann equation, which generally requires numerical solution. A tutorial
      approach is taken, the main aim of which is a thorough understanding of the
      method.

PMID- 14977532
TI  - The role of oxidative damage in mitochondria during aging: a review.
AB  - Aging is a complex process (or series of processes). Recent evidence suggests
      that several of its most important mechanisms are linked by means of cellular
      damage caused by reactive oxygen species (ROS). Oxidative damage may be a major
      factor in the loss of physiological functions that occur in degenerative diseases
      and aging. This is because, in aerobic organisms, the mitochondrial electron
      transport chain plays an important role in energy production and is a significant
      source of ROS that damage DNA, RNA, and proteins in cells. While oxidative events
      in other cell organelles are likely to contribute to the pathobiology of aging,
      this review highlights alterations in mitochondrial function that, due to
      accumulated oxidative damage, occur with age.

PMID- 14977533
TI  - Endothelial microparticles as markers of endothelial dysfunction.
AB  - Endothelial microparticles (EMP) are small vesicles released from disturbed
      endothelial cells (EC). Owing to the central importance of EC injury in
      thrombotic and inflammatory conditions, assay of EMP as a marker of EC
      disturbance has come under intensive development by several laboratories. The
      review begins with established markers of EC injury, commonly soluble markers
      such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion
      molecule-1 (VCAM-1), E-selectin, von Willebrand factor (vWF), etc., pointing out
      that many of these are in fact mixtures of true soluble molecules with membrane
      bound forms, for example, EMP. Assays of EMP from different labs are reviewed and
      standardization of assay is recommended. EMP are heterogeneous: those released in
      activation vs. apoptosis are distinctive in phenotypic markers and procoagulant
      properties. Application of EMP phenotype analysis can distinguish EC state of
      activation from apoptosis. Some EMP carry functional vWF with properties
      different from soluble vWF. Certain EMP bind to and activate monocytes; EMP
      monocyte conjugates were found to be a marker of inflammatory disease such as
      multiple sclerosis (MS), and to enhance transendothelial migration of leukocytes
      in vitro. Clinical studies have revealed elevated plasma levels of EMP in lupus
      anticoagulant (LA), multiple sclerosis (MS), thrombotic thrombocytopenic purpura
      (TTP), coronary artery disease (CAD), hypertension, preeclampsia, and diabetes.
      Further refinement of EMP assay could open new windows for evaluating and
      monitoring endothelial injury in thrombotic and inflammatory disorders.

PMID- 14977534
TI  - Persistent and dormant tubercle bacilli and latent tuberculosis.
AB  - Tubercle bacillus has remarkable ability to persist in the human host and has
      caused latent infection in one third of the world population. The current
      tuberculosis (TB) chemotherapy while effective in killing growing bacilli is
      largely ineffective in killing persistent or dormant bacilli, leading to
      prolonged therapy. There is considerable recent interest to study mechanisms of
      persistence and dormancy in mycobacteria. Meanwhile, there is also confusion
      about the use of terminology of dormant and persistent bacilli. Different models
      of mycobacterial persistence have been established. Various mycobacterial factors
      have recently been identified that may be involved in persistence or dormancy and
      resuscitation of dormant organisms. The phenotypic resistance to antituberculosis
      drugs in persistent and dormant bacilli presents a major challenge for effective
      control of the disease. The host immune system is critical in controlling latent
      TB infection from reactivation. A recent interesting observation is the
      reactivation of latent TB infection by anti-TNF-alpha antibody used as a
      treatment for rheumatoid arthritis and Crohn's disease. The role of
      psychoneuroendocrinological factors in TB, which is often ignored in the era of
      modern chemotherapy but could be important for controlling latent infection, is
      also briefly reviewed. There is recent interest to develop new TB drugs that
      target persistent and dormant bacilli and also immunotherapeutic agents that
      enhance chemotherapy and better control latent infection. The complex interaction
      between the bacteria, drugs, host and the environment underscores the need for a
      combined approach that incorporates chemotherapy, immunotherapeutic agents,
      improved socioeconomic, nutritional and even conducive psychological factors for
      more effective control of TB and latent TB.

PMID- 14977535
TI  - Extracellular virulence factors of streptococci associated with animal diseases.
AB  - A virulence factor denotes a bacterial product or strategy that contributes to
      virulence or pathogenicity. Streptococci produce a variety of protein toxins and
      enzymes that are capable of killing host cells and breaking down cell
      constituents, presumably to provide nutrients for the bacteria or to promote
      their spread. Some of these secreted products are hemolysins, streptokinases,
      hyaluronidases, exotoxins and proteases. In some cases, they play an important
      role in resistance to the host immune system, acting alone or in combination with
      cell-associated virulence factors (such as the capsule and surface proteins).
      Thus, the virulence of streptococci is considered as a multifactorial process. In
      contrast to well known human pathogens, and in spite of their veterinary
      importance, knowledge of virulence factors of most animal disease-associated
      streptococci is limited or almost inexistent. In the present article, the
      available information regarding the extracellular virulence factors of the most
      important animal disease-related streptococci is reviewed.

PMID- 14977536
TI  - DNA methylation and male infertility.
AB  - Male infertility is one of the biggest concerns of today's health care community.
      In the US and other developed countries, approximately 70% of infertility among
      couples is attributed to male reproductive failure. Alterations in reproductive
      organ development and sperm production have been listed as the major causes of
      this phenomenon. Sex determination and differentiation, X chromosome
      inactivation, gene imprinting and normal germ cell development are important
      biological processes that, in turn, control mammalian reproduction. Specific
      patterns of gene expression and repression are important in such processes. The
      strong correlation between DNA methylation, a major epigenetic modification of
      the genome, and gene expression patterns is well documented. The effects of DNA
      methylation on the expression of genes affecting male reproductive organ
      development, spermatogenesis, and male sexual behavior have been reported,
      suggesting that alterations in DNA methylation could induce abnormal male sexual
      development and reproductive performance. Inheritance of epigenetic processes and
      changes in DNA methylation patterns induced by certain diets have been
      demonstrated in recent years. However, the effects of DNA methylation on male
      fertility have not been well studied. Since inherited altered DNA methylation
      patterns could be a cause of increased susceptibility to xenobiotics or abnormal
      phenotype in future generations, multigenerational studies oriented to determine
      the effects of xenobiotics affecting DNA methylation in male fertility are
      recommended.

PMID- 14977537
TI  - NF-kappaB action in sepsis: the innate immune system and the heart.
AB  - Sepsis is the clinical syndrome that results from a host's inflammatory response
      to infection via activation of the innate immune system. This response involves a
      complex network of inflammatory mediators that is self-reinforcing. When this
      immune response progresses uncontrollably, it can ultimately result in
      cardiovascular collapse and death. This complex inflammatory response is
      comprised of multiple mediators including cytokines such as TNF-alpha and IL
      1beta, that are synthesized and secreted in response to signaling by receptors of
      the Toll-like receptor (TLR) family of pattern recognition receptors (PRR) that
      bind to pathogen associated molecules. A central downstream element of TLR
      dependent signaling is the pleiotropic transcription factor NF-kappaB. NF-kappaB
      has been implicated in the regulation of multiple biological phenomena and
      disease states, including apoptosis, cell growth, stress response, innate
      immunity and septic shock. NF-kappaB-dependent genes are numerous and several
      have been implicated in the pathogenesis of sepsis and associated with cardiac
      dysfunction in sepsis. NF-kappaB activation occurs in multiple organs and cell
      types, and may be primarily protective in one tissue but injurious in another.
      Thus, a detailed understanding of the molecular basis of the pathophysiology of
      sepsis is needed in order to specifically block pro-inflammatory and pro
      apoptotic signaling in the heart, while avoiding adverse effects in other organs.

PMID- 14977538
TI  - Multiparametric effect: concentration analyses.
AB  - Immunosuppressant drug toxicity currently competes with acute rejection, as the
      major cause of efficacy failure of potent new agents in clinical transplantation.
      The development of mechanistic drug targets as surrogate endpoints for use in the
      clinic has been facilitated by fluorescent imaging techniques which measure
      multiple cytokines and cell surface receptors on stimulated (peripheral blood)
      lymphocyte responses. However, the promise of delivering customized drug therapy
      to the transplant recipient remains unfulfilled. In this brief review,
      computational algorithms that can relate multiparametric effects to clinical drug
      concentrations of immunosuppressants are discussed. Based on Hill equations,
      these pharmacodynamic modeling techniques have been used to simulate single-agent
      effects, combination regimen effects, as well as the individual response to
      combination regimens. The potential implications of these models crystallize the
      clinical challenges confronting practitioners of clinical, post-transplant
      immunosuppression.

PMID- 14977539
TI  - Disappearing "T1 black holes" in an animal model of multiple sclerosis.
AB  - Brain MRI in multiple sclerosis (MS) frequently shows areas of hypointensity in
      the white matter on T1 weighted sequences ("T1 black holes"). These areas are
      thought to be consistent with irreversible axonal loss. In this study T1 black
      holes were characterized in Theiler's Murine Encephalitis Virus infection, an
      established model of demyelinating diseases in mice. The spectrum of TMEV is
      broad in different strains. C57BL/6J mice develop a self-limited brain disease,
      which resolves within 4-6 weeks. We followed six mice with serial MRI and MRS on
      days 0, 3,7,21 and 45. The studies were performed in a 7 Tesla magnet.
      Periventricular and parahippocampal T1 black holes seen as early as 3 days, with
      decreasing NAA/Cre ratio on MRS. The extent of pathology was most severe on days
      3 and 7. T1 black holes are thought to be consistent with areas of irreversible
      axonal loss. This is challenged by our observations of resolution of T1 black
      holes by day 45. This was concomitant with the normalization of MRS findings in
      the areas of interest. We conclude that T1 black holes may represent a transient
      phenomenon in this model of MS. The recovery of these areas studied suggests an
      active repair mechanism.

PMID- 14977540
TI  - Main features on tailed phage, host recognition and DNA uptake.
AB  - Phage nucleic acid transport is atypical among membrane transport and thus poses
      a fascinating problem: transport is unidirectional; it concerns a unique molecule
      the size of which may represent 50 times that of the bacterium. The rate of DNA
      transport can reach values as high as 3 to 4 thousands base pairs/sec. This
      raises many questions, which will be addressed in this review. Is there a single
      mechanism of transport for all types of phages? How does the phage genome
      overcome the hydrophobic barrier of the host envelope? Is DNA transported as a
      free molecule or in association with proteins? Is such transport dependent on
      phage and/or host cell components? What is the driving force for transport? Data
      will be presented for a few selected tailed phages, which are the most common
      type of phages and for which DNA transport has been most extensively studied.
      Part of the review is devoted to recent in vitro data which have allowed to
      partly decipher the mechanism of phage T5 DNA transport.

PMID- 14977541
TI  - Direct effects of long-chain non-esterified fatty acids on vascular cells and
      their relevance to macrovascular complications of diabetes.
AB  - Diabetes leads to a marked increase in cardiovascular disease caused by
      atherosclerosis. Cardiovascular complications of diabetes are associated with
      lipid abnormalities, mainly manifested as elevated levels of triglycerides.
      Hydrolysis of triglycerides by lipases in the arterial wall is believed to cause
      increased levels of non-esterified fatty acids (NEFAs) in lesions of
      atherosclerosis. Recent research has shown that long-chain NEFAs have a multitude
      of direct effects on cell types involved in atherogenesis. Thus, some of the most
      common long-chained fatty acids present in triglycerides, oleic acid and linoleic
      acid, have been shown to induce adhesion molecule expression, cytokine expression
      and apoptosis in endothelial cells, to increase cholesterol uptake and reduce
      cholesterol efflux in macrophages, and to increase arterial smooth muscle cell
      proliferation and migration. Certain NEFAs liberated from triglycerides may
      therefore play an important role in accelerating atherosclerosis caused by
      diabetes by directly affecting the key cell types involved in atherogenesis.

PMID- 14977542
TI  - Regulation of endothelial cell function BY FAK and PYK2.
AB  - Endothelial cells form a continuous single layer lining throughout the vascular
      tree. Such positioning allows the endothelium to monitor numerous environmental
      signals within the blood vessel, including blood composition, structural matrix,
      and blood flow dynamics. Following signal integration, endothelial cells then
      induce context-specific changes in vessel properties. The nonreceptor tyrosine
      kinases focal adhesion kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2) are
      activated by integrins, growth factors, and mechanical stimuli, suggesting a
      potentially important role in the integration of environmental stimuli. This
      review will explore the current understanding of FAK and Pyk2 signaling in
      endothelial regulation of vascular function.

PMID- 14977543
TI  - Virulence properties of Streptococcus mutans.
AB  - Streptococcus mutans is considered one of the primary causative agents of dental
      caries and can also be a source of infective endocarditis. The main virulence
      factors associated with cariogenicity include adhesion, acidogenicity, and acid
      tolerance. Each of these properties works coordinately to alter dental plaque
      ecology. The ecological changes are characterized by increased proportions of S.
      mutans and other species that are similarly acidogenic and aciduric. The
      selection for a cariogenic flora increases the magnitude of the drop in pH
      following the fermentation of available carbohydrate and increases the
      probability of enamel demineralization. This review focuses on the bacterial
      components that contribute to each of the major virulence properties. Further
      understanding of how these components work together in the development of dental
      caries will be aided by the recent completion of the sequence of the S. mutans
      genome and experimental designs that model the dental plaque biofilm.

PMID- 14977544
TI  - Magnesium in clinical medicine.
AB  - Until recently the physiological role of magnesium was essentially ignored.
      However, with the development of new technologies to measure the intracellular
      free concentration of magnesium ([Mg2+]i), the biologically important fraction,
      there has been an explosion of interest in the molecular, biochemical,
      physiological and pharmacological functions of magnesium. In addition improved
      methods for assessing magnesium status in the clinic have contributed to the
      further understanding of magnesium regulation in health and disease. Magnesium
      deficiency is now considered to contribute to many diseases and the role for
      magnesium as a therapeutic agent is being tested in numerous large clinical
      trials. This review focuses on clinical manifestations associated with magnesium
      deficiency and highlights the clinical significance of hypermagnesemia. Specific
      clinical conditions in which magnesium deficiency has been implicated to play a
      pathophysiological role, namely hypertension, ischemic heart disease,
      arrhythmias, prec-eclampsia, asthma and critical illness will be discussed and
      the possible therapeutic role of magnesium will be considered. Although there is
      still much to be learnt regarding the exact role of magnesium in clinical
      medicine, there are two conditions where magnesium is now considered the
      therapeutic agent of choice, pre-eclampsia and torsades de pointes. Future
      research, both at the fundamental and clinical levels, will certainly facilitate
      our understanding of how magnesium contributes to pathological processes and
      under what circumstances it should be used therapeutically.

PMID- 14977545
TI  - ENA/VASP proteins: multifunctional regulators of actin cytoskeleton dynamics.
AB  - The spatial and temporal regulation of the actin cytoskeleton is fundamental to
      several cellular processes as diverse as cell motility and immune responses. At
      the molecular level, the remodelling of the actin cytoskeleton depends on two key
      events: actin filament nucleation and elongation. Seminal studies on the actin
      based intracellular motility of the bacterial pathogen Listeria monocytogenes
      have been instrumental for the characterisation of a class of actin filament
      elongating factors, the proteins of the Ena/VASP family. Ena/VASP proteins
      enhance actin filament elongation via the recruitment of profilin:actin complexes
      to sites of active actin remodelling such as the tips of spreading lamellipodia
      and the surface of intracellular Listeria. Moreover, Ena/VASP proteins not only
      enhance actin filament elongation but also influence the activity of the Arp2/3
      complex and counteract the inhibition of actin polymerisation by capping
      proteins. These findings, taken together with the observation that Ena/VASP
      proteins can influence actin filament architecture by affecting the actin
      filament branching activity of the Arp2/3 complex, define Ena/VASP proteins as
      multifunctional organisers of the actin cytoskeleton.

PMID- 14977546
TI  - On the mechanism and pathway of colicin import across the E. Coli outer membrane.
AB  - Colicins and phages parasitize outer membrane receptors whose physiological
      purpose is the transport of metabolites, metals, vitamins, and sugars. From
      mutagenesis studies, it is known that several colicins require the function of
      two outer membrane protein (Omp) receptors for cytotoxicity. A formidable list of
      problems associated with an understanding of a two receptor mechanism for colicin
      translocation includes the definition of the sites of initial binding and
      interactions of the colicin with the OM translocator protein, the working lumenal
      aperture of the translocator, the question of whether the colicin must be
      unfolded for translocation, the source of energy for unfolding and translocation,
      the order of colicin translocation, and the sites and mechanism of interaction of
      the colicins with the Tol-Pal proteins on the periplasmic side of the outer
      membrane. 3D crystal structures recently obtained of the cobalamin (vitamin B12)
      receptor (BtuB), and of the complex of BtuB with the 135 residue receptor binding
      domain (R135) of colicin E3, have provided some new insights on the interactions
      between two Omp receptors that are necessary for translocation of colicins.
      Together with spectroscopic data on the R135-BtuB interaction and
      electrophysiological data on the colicin E3-OmpF interaction, this has led to a
      proposal for the utilization of two receptors, BtuB-OmpF, in an outer membrane
      translocon for colicin E3.

PMID- 14977547
TI  - Evolution of assisted protein folding: the distribution of the main chaperoning
      systems within the phylogenetic domain archaea.
AB  - Newly made proteins must achieve a functional shape, the native configuration,
      before they can play their physiological roles in the cell. Proteins must also
      travel to the locale (e.g., the mitochondrion) in the cell where their functions
      are required. In these processes of folding into the native configuration and
      translocation to the place of work, proteins may be assisted by molecules called
      molecular chaperones. Stressors can unfold (denature) proteins, and genetic
      defects can cause misfolding and, in addition, both abnormalities can lead to
      polypeptide aggregation. Chaperones play a role in assisting refolding of
      partially denatured or misfolded proteins, thus preventing aggregation. Clearly,
      molecular chaperones are key cell components under normal, physiological
      circumstances, as well as in potentially harmful situations resulting from
      environmental or inherited factors. Hence, molecular chaperones constitute
      attractive targets for a variety of efforts aiming at improving the cell's
      performance, particularly under stress, to prevent disease, or at least to slow
      down its progression and to contain the deleterious effects of stress. In our
      efforts in this direction, we have undertaken to investigate the chaperoning
      systems of cells belonging to the phylogenetic domain Archaea. The findings
      reported here pertain to the distribution of the molecular chaperone machine, the
      chaperonins, and the prefoldins, among archaea. The genes hsp70(dnaK),
      hsp40(dnaJ), and grpE encoding the components of the molecular chaperone machine
      were present only in some archeaeal species: this contrasts with bacteria and
      eucarya, which do have the genes with no known exception. The group I, or
      bacterial, chaperonin-genes groEL and groES occured in the genomes of
      Methanosarcina species but were not found in any of the other archaea whose
      genomes have been sequenced. While all the archaea studied had between one and
      three chaperonins of group II (thermosome subunits), Methanosarcina acetivorans
      was exceptional since it had five of these chaperonins. This is the largest
      number of group II chaperonins ever found in a prokaryote. Furthermore, two of
      the M. acetivorans chaperonins were different from, albeit related to, the other
      known archaeal and eucaryal chaperonins of group II. Prefoldins were found in all
      archaea examined. Overall, the results provide clues to the evolution of the
      chaperoning systems, which must have played a critical role in survival since
      life started. Also, the data suggest new avenues of research for elucidating the
      evolution of assisted protein folding and for uncovering roles and interactions
      not yet described for these molecules.

PMID- 14977548
TI  - Specificity of WNT-receptor interactions.
AB  - The highly conserved Wnt signaling proteins play critical roles in guiding
      pattern formation, cell fate decision, and morphogenetic movement during animal
      development. They bind to the Frizzled family of seven-pass transmembrane
      proteins and initiate at least three different intracellular signaling pathways,
      resulting in regulation of gene expression and/or changes in cell behavior. A
      single transmembrane protein from the low-density-lipoprotein family functions as
      a co-receptor in the canonical/beta-catenin pathway. The specificity of Wnt
      signaling depends in part on the affinities between various Wnt-Frizzled pairs. A
      Wnt-dependent receptor dimerization or clustering step has been hypothesized as
      the step that initiates the canonical signaling cascade in cells.

PMID- 14977549
TI  - Inflammatory responses to ischemia and reperfusion in the cerebral
      microcirculation.
AB  - Ischemia and reperfusion (I/R) has been shown to elicit an inflammatory response
      that is characterized by an increased production of reactive oxygen species, and
      the rolling, firm adhesion, and transendothelial migration of leukocytes in
      postcapillary venules. A rate-determining role for leukocyte-endothelial cell
      (L/E) adhesion in the initiation and propagation of reperfusion injury is
      supported by several reports that describe attenuated microvascular dysfunction
      and tissue injury following I/R in animals receiving neutralizing antibodies
      directed against certain leukocyte adhesion receptors and in mutant mice that are
      genetically deficient in these adhesion receptors The technique of intravital
      videomicroscopy has been applied to several tissues, including the brain, in
      order to directly observe the microcirculatory alterations and inflammatory
      responses that are elicited by I/R. The leukocyte- and platelet-endothelial cell
      adhesion responses to cerebral I/R are addressed and compared to responses
      observed in other postischemic vascular beds. The limited data available for the
      brain microcirculation support the potential of anti-leukocyte and anti-platelet
      strategies for stroke therapy.

PMID- 14977550
TI  - Catabolism of caffeine in plants and microorganisms.
AB  - Caffeine has been found in tissues of several plants. Because of its stimulating
      effect on the central nervous system, a great number of reports have been
      published on its content in beverages and foodstuffs. However, a much more
      restricted number of reports have dealt specifically with caffeine metabolism in
      plants. This review presents, in chronological manner, the contribution of these
      reports to the vast knowledge accumulated on caffeine catabolism in plants and
      microorganisms over the last 40 years. In plants, the accumulated data indicate
      the operation of a main catabolic pathway: caffeine --> theophylline --> 3
      methylxantine --> xanthine --> uric acid --> allantoin --> allantoic acid -->
      glyoxylic acid + urea --> NH3 + CO2. Some studies have shown that, depending on
      the plant species, other minor routes may operate with the formation of
      theobromine and 7-methylxantine, which are salvaged for caffeine formation since
      they also appear in the biosynthetic pathway. A specific group of coffee known as
      liberio-excelsioides has the ability to convert caffeine to the corresponding
      methyluric acid, which is methylated to other uric acid derivatives. In bacteria
      caffeine is either degraded to theobromine or paraxanthine. Both
      dimethylxanthines are demethylated to 7-methylxantine which in turn is
      demethylated to xanthine and then enters the catabolic pathway of purines. In
      bacteria, theobromine, paraxanthine and 7-methylxantine may also be oxidized to
      their corresponding methyluric acids.

PMID- 14977551
TI  - Effect of dehydroepiandrosterone on oxalate metabolism in rats.
AB  - Urinary oxalate plays an important role in the formation of calcium oxalate
      stone, and endogenous oxalate metabolism mainly occurs in the liver. Since
      dehydroepiandrosterone (DHEA) is known to have an effect on hepatocellular
      proliferation and on some hepatic enzymes, we examined the influence of DHEA on
      the activity of hepatic oxalate-related enzymes and on urinary oxalate excretion
      in rats. Fourteen male rats were castrated and divided into two groups. The
      control group was fed a standard diet, while the other rats were fed a diet
      containing 0.5% DHEA. After 4 weeks, the liver weight and the urinary levels of
      oxalate, glycolate, and glycine were significantly higher in the DHEA-treated
      rats than in the controls, while body weight did not differ between the two
      groups. Hepatic alanine:glyoxylate aminotransferase and glyoxylate reductase
      showed significantly higher activity in the DHEA-treated rats than in the
      controls, while glycolate oxidase activity was significantly reduced. Treatment
      with DHEA induced hyperoxaluria along with hepatocyte proliferation. This
      hyperoxaluria was probably caused by hepatocyte proliferation, but it could not
      be explained simply by the changes of hepatic oxalate-related enzymes.
      Investigation of the modulation of peroxisomal enzymes by peroxisomal
      proliferators or inhibitors may provide further insights into hepatocyte oxalate
      metabolism.

PMID- 14977552
TI  - EPHB receptor signaling in dendritic spine development.
AB  - Dendritic spines are small bulbous protrusions on the surface of dendrites that
      serve as principle postsynaptic targets for excitatory synapses (1-3). Structural
      modifications of dendritic spines have been implicated as a cellular basis for
      learning and memory. Morphological abnormalities of spines are observed in some
      neurological diseases such as mental retardation and schizophrenia (4). Thus,
      studies on the morphological regulation of dendritic spines could have strong
      relevance to our understanding of the molecular mechanisms of the higher brain
      function and the pathophysiology of neurological disorders. Here we review recent
      progress on the role of the cell surface heparan sulfate proteoglycan syndecan-2
      and ephrin-Eph signaling in dendritic spine development. Information from these
      new developments suggests a model in which cell surface ephrin-Eph signaling
      induces clustering of syndecan-2 and recruitment of cytoplasmic molecules, which
      leads to localized actin polymerization via Rho family GTPases, N-WASP, and the
      Arp2/3 complex.

PMID- 14977553
TI  - Ureide biosynthesis in legume nodules.
AB  - In tropical legumes like Glycine, Phaseolus and Vigna sp., ammonia as direct
      product of symbiotic nitrogen fixation is converted to ureides (allantoin and
      allantoic acid) and they were translocated to the shoots as nitrogen source. In
      the xylem sap of soybean in reproductive phase the ureides reached to 60-75% of
      soluble nitrogen. In nodules infected cells (plastid and mitochondria) and
      uninfected cells (peroxisome) shares de novo purine biosynthesis and urate
      oxidation to produce ureides respectively. Current research revealed unique
      feathers on this symbiotic metabolism, especially on regulation of purine
      biosynthesis, uricase gene expression and feedback inhibition of ureides to
      nitrogen fixing activity.

PMID- 14977554
TI  - Manganese-dependent protein O-phosphatases in prokaryotes and their biological
      functions.
AB  - During the past decade, numerous Mn2+-dependent protein serine, threonine and/or
      tyrosine phosphatases (O-phosphatases) from prokaryotes have been characterized.
      Based on their amino acid sequences, they belong to PPP, PPM or PHP
      superfamilies. Both the PPP and PPM families of protein phosphatases are
      metalloenzymes which active centers contain two metal ions that function as
      cofactors. Results from sequence analysis also suggest that PHP family protein
      phosphatase is a metalloenzyme. The identified functions for PPP family protein
      phosphatases from different prokaryotic organisms include regulation of stress
      response, nitrogen fixation and vegetative growth. At least one phosphatase, PrpB
      from Escherichia coli, is also implicated in bacterial pathogenesis. Prokaryotic
      PPM family protein phosphatases are involved in controlling spore formation,
      stress-response, cell density during stationary phase, carbon and nitrogen
      assimilation, vegetative growth, development of fruiting bodies and cell
      segregation. The function of CpsB, a PHP family protein tyrosine phosphatase from
      Streptococcus pneumonia, is to regulate biosynthesis of capsular polysaccharide,
      an important virulence determinant. Thus, this group of functionally diverse
      protein phosphatases plays an important role in prokaryotes. Discovery of Mn2+
      dependent prokaryotic protein O-phosphatases and their functions also contributes
      to new insight into Mn2+ homeostasis and many roles played by Mn2+ and protein O
      phosphorylation in prokaryotic cells.

PMID- 14977555
TI  - Metabolism of diadenosine tetraphosphate (Ap4A) and related nucleotides in
      plants; review with historical and general perspective.
AB  - This review presents our knowledge of potential biochemical conversions of minor
      mononucleotides, such as adenosine-5'-tetraphosphate (p4A) and adenosine-5'
      pentaphosphate (p5A), and dinucleotides, such as diadenosine-5',5"'-P1,P3
      triphosphate (Ap3A) and diadenosine-5',5"'-P1,P4-tetraphosphate (Ap4A), in
      plants. Although the occurrence of p4A, Ap3A and/or Ap4A has been demonstrated in
      various bacteria, fungi and animals, identification of these compounds in plants
      has not been reported as yet. However, the ubiquity of both the compounds and
      enzymes that can synthesize them (certain ligases and transferases), the
      demonstration that certain plant ligases can synthesize pnAs and ApnNs in vitro,
      and the existence in plants of specific and nonspecific degradative enzymes
      strongly suggest that these various pnNs and NpnN's do indeed occur and play a
      biological role in plant cells. In fact, some of the plant enzymes involved in
      the synthesis and degradation of these minor mono- and dinucleotides have been
      studied even more thoroughly than their counterparts from other organisms.

PMID- 14977556
TI  - Endothelial cell seeding of polymeric vascular grafts.
AB  - Pioneers in the field of small diameter graft development sought to promote graft
      endothelialization and, thereby, increase patency by transplanting a varying
      degree of autologous endothelial cells onto vascular grafts prior to
      implantation. This process has become known as endothelial cell seeding. The
      underlying hypothesis is quite simple; that is, by promoting the establishment of
      the patient's own endothelial cells on the blood contacting surface of a vascular
      prosthesis, a "normal" endothelial cell lining and associated basement membrane,
      together known as the neointima, will form on the graft and counteract the
      rheologic, physiologic, and biomaterial forces working synergistically to promote
      graft failure. After 30 years of research in this area, this simple hypothesis
      has proven to be deceptively naive. The purpose of this review is to summarize
      the historic context and current base of knowledge regarding many of the
      technical issues relevant to the endothelial cell seeding process. Special
      attention is given to electrostatic endothelial cell seeding, the latest research
      methodology designed specifically to accelerate endothelial cell adhesion and
      morphological maturation onto expanded poly(tetrafluoroethylene) (e-PTFE) small
      diameter vascular grafts.

PMID- 14977557
TI  - Electrospinning collagen and elastin: preliminary vascular tissue engineering.
AB  - Significant challenges must be overcome before the true benefit and economic
      impact of vascular tissue engineering can be fully realized. Toward that end, we
      have pioneered the electrospinning of micro- and nano-fibrous scaffoldings from
      the natural polymers collagen and elastin and applied these to development of
      biomimicking vascular tissue engineered constructs. The vascular wall composition
      and structure is highly intricate and imparts unique biomechanical properties
      that challenge the development of a living tissue engineered vascular replacement
      that can withstand the high pressure and pulsatile environment of the
      bloodstream. The potential of the novel scaffold presented here for the
      development of a viable vascular prosthetic meets these stringent requirements in
      that it can replicate the complex architecture of the blood vessel wall. This
      replication potential creates an "ideal" environment for subsequent in vitro
      development of a vascular replacement. The research presented herein provides
      preliminary data toward the development of electrospun collagen and elastin
      tissue engineering scaffolds for the development of a three layer vascular
      construct.

PMID- 14977558
TI  - Cytokines and fever.
AB  - Cytokines are highly inducible, secreted proteins mediating intercellular
      communication in the nervous and immune system. Fever is the multiphasic response
      of elevation and decline of the body core temperature regulated by central
      thermoregulatory mechanisms localized in the preoptic area of the hypothalamus.
      The discovery that several proinflammatory cytokines act as endogenous pyrogens
      and that other cytokines can act as antipyretic agents provided a link between
      the immune and the central nervous systems and stimulated the study of the
      central actions of cytokines. The proinflammatory cytokines interleukin 1 (IL-1),
      interleukin 6 (IL-6) and the tumor necrosis factor alpha (TNF) as well as the
      antiinflammatory cytokines interleukin 1 receptor antagonist (IL-1ra) and
      interleukin 10 (IL-10) have been most investigated for their pyrogenic or
      antipyretic action. The experimental evidence demonstrating the role of these
      secreted proteins in modulating the fever response is as follows: 1) association
      between cytokine levels in serum and CSF and fever; 2) finding of the presence of
      cytokine receptors on various cell types in the brain and demonstration of the
      effects of pharmacological application of cytokines and of their neutralizing
      antibodies on the fever response; 3) fever studies on cytokine- and cytokine
      receptor- transgenic models. Studies on the peripheral and the central action of
      cytokines demonstrated that peripheral cytokines can communicate with the brain
      in several ways including stimulation of afferent neuronal pathways and induction
      of the synthesis of a non cytokine pyrogen, i.e. PGE2, in endothelial cells in
      the periphery and in the brain. Cytokines synthesized in the periphery may act by
      crossing the blood brain barrier and acting directly via neuronal cytokine
      receptors. The mechanisms that ultimately mediate the central action of cytokines
      and of LPS on the temperature-sensitive neurons in the preoptic hypothalamic
      region involved in thermoregulation, directly or via second mediators, remain to
      be fully elucidated.

PMID- 14977559
TI  - Modulators of urinary stone formation.
AB  - Urine contains compounds that modulate the nucleation, growth and aggregation of
      crystals as well as their attachment to renal epithelial cells. These compounds
      may function to protect the kidneys against: 1, the possibility of
      crystallization in tubular fluid and urine, which are generally metastable with
      respect to calcium salts, 2, crystal retention within the kidneys thereby
      preventing stone formation and 3, possibly against plaque formation at the
      nephron basement membrane. Since oxalate is the most common stone type, the
      effect of various modulators on calcium oxalate (CaOx) crystallization has been
      examined in greater details. Most of the inhibitory activity resides in
      macromolecules such as glycoproteins and glycosaminoglycans while nucleation
      promotion activity is most likely sustained by membrane lipids. Nephrocalcin,
      Tamm-Horsfall protein, osteopontin, urinary prothrombin fragment 1, and bikunin
      are the most studied inhibitory proteins while chondroitin sulfate (CS), heparan
      sulfate (HS) and hyaluronic acid (HA) are the best studied glycosaminoglycans.
      Crystallization modulating macromolecules discussed here are also prominent in
      cell injury, inflammation and recovery. Renal epithelial cells on exposure to
      oxalate and CaOx crystals produce some of the inflammatory molecules such as
      monocyte chemoattractant protein-1 (MCP-1) with no apparent role in crystal
      formation. In addition, macrophages surround the CaOx crystals present in the
      renal interstitium. These observations indicate a close relationship between
      inflammation and nephrolithiasis.

PMID- 14977560
TI  - Transverse Myelitis: pathogenesis, diagnosis and treatment.
AB  - Transverse Myelitis (TM) is a clinical syndrome in which an immune-mediated
      process causes neural injury to the spinal cord, resulting in varying degrees of
      weakness, sensory alterations and autonomic dysfunction. TM may exist as part of
      a multi-focal CNS disease (e.g. MS), multi-systemic disease (e.g. systemic lupus
      erythematosus), or as an isolated, idiopathic entity. In this article, we will
      summarize recent classification and diagnostic schemes (1), which provide a
      framework for the acute management of patients with TM. Additionally, we will
      review current concepts on the natural history, immunopathogenesis and treatment
      strategies for patients with TM.

PMID- 14977561
TI  - Chemokines and chemokine receptors in autoimmune encephalomyelitis as a model for
      central nervous system inflammatory disease regulation.
AB  - This article focuses on the distinct role of chemokines and chemokine receptors
      during CNS inflammation in experimental autoimmune encephalomyelitis (EAE) as an
      animal model for multiple sclerosis (MS). We review the evidence that chemokines
      and chemokine receptors have an intrinsic role in regulating and amplifying the
      inflammatory reactions in EAE or MS leading to disease outcome. A variety of
      studies examining temporal chemokine expression patterns, using chemokine and
      chemokine receptor knockout mice as well as administering passive anti-chemokine
      antibodies indicates that these molecules are critical regulatory components for
      leukocyte recruitment and/or leukocyte retention in the CNS. Therefore, chemokine
      and chemokine receptor expression is tightly interrelated to composition of
      inflammatory cells in CNS lesions and the onset of clinical diseases and provide
      viable targets for therapeutic intervention.

PMID- 14977562
TI  - Purine and pyrimidine nucleotide synthesis and degradation during in vitro
      morphogenesis of white spruce (Picea glauca).
AB  - In the last few years, somatic embryogenesis and organogenesis of white spruce
      (Picea glauca) have been used as model systems to investigate biochemical and
      physiological events related to morphogenesis. This has been possible because
      studies conducted in vitro allow for manipulations of the culture conditions, in
      which changes in morphogenetic events can be easily related to physiological
      alterations. De-novo synthesis, salvage, and degradation of both purine and
      pyrimidine nucleotides are operative at all stages of somatic embryo maturation
      and germination. Fluctuations in the activity of these pathways delineate
      important morphogenic events. The early phases of embryo development are
      accompanied by a decreased salvage activity of purine nucleotides, which reflects
      a reduction of cell proliferation and the initiation of organized growth.
      Activities of the salvage enzymes are present throughout the maturation period,
      and also during the imposition of the drying period, which is required for
      successful embryo germination. The operative salvage pathway in dried embryos is
      needed for the enlargement of the nucleotide pool necessary to sustain the
      reactivation of the overall cellular metabolism at germination, before the
      reactivation of the de-novo pathway, which is a later event. Manipulations of the
      culture medium which improve the germination frequency of the embryos also result
      in increased salvage activity. Similar changes in nucleotide synthesis were also
      observed during the initiation of shoot development from epicotyl explants of
      white spruce and cotyledons of radiate pine. Results from these studies can be
      used for improving growth and development in culture.

PMID- 14977563
TI  - Bone morphogenetic protein-3 family members and their biological functions.
AB  - Bone morphogenetic protein-3 and 3b (BMP-3 and BMP-3b) together represent a
      unique subgroup of the BMP family. BMP-3b shares 82% amino acid identity with BMP
      3 in the mature region (ligand domain), but only 37% in the pro-region (pro
      domain). In osteoblasts, BMP-3 and 3b have similar antagonistic activity against
      BMP-2, but they are differentially regulated. In developing embryos, BMP-3 and 3b
      have different dorsalizing activities. BMP-3b triggers secondary head formation
      in an autonomous manner, whereas BMP-3 induces aberrant tail formation. Loss-of
      function analysis demonstrates that coordinated activity of xBMP-3b and cerberus,
      a head inducer, are required for head formation in Xenopus embryos. At the
      molecular level, BMP-3b antagonizes both nodal-like proteins (Xnr1 and derriere)
      and ventralizing BMPs (BMP-2 and ADMP), whereas BMP-3 only antagonizes
      ventralizing BMPs. Moreover, BMP-3b, but not BMP-3, associates with the monomeric
      form of Xnr1, a nodal-like protein. These molecular features of BMP-3 and 3b are
      due to their distinct pro-regions. These findings suggest that the processing of
      precursor regions and assembly of BMP-3 and 3b are important in various
      developmental processes and organogenesis.

PMID- 14977564
TI  - Noncanonical Wnt signaling pathways in C. elegans converge on POP-1/TCF and
      control cell polarity.
AB  - In the nematode Caenorhabditis elegans, a canonical Wnt signaling pathway
      controls a cell migration whereas noncanonical Wnt pathways control the
      polarities of individual cells. Despite the differences in the identities and
      interactions among canonical and noncanonical Wnt pathway components, as well as
      the processes they regulate, almost all C. elegans Wnt pathways involve the sole
      Tcf homolog, POP-1. Intriguingly, POP-1 is asymmetrically distributed between the
      daughters of an asymmetric cell division, with the anterior sister cell usually
      having a higher level of nuclear POP-1 than its posterior sister. At some
      divisions, asymmetric distribution of POP-1 is controlled by noncanonical Wnt
      signaling, but at others the asymmetry is generated independently. Recent
      experiments suggest that despite this elaborate anterior-posterior POP-1
      asymmetry, the quantity of POP-1 protein may have less to do with the subsequent
      determination of fate than does the quality of the POP-1 protein in the cell. In
      this review, we will embark on a quest to understand Quality (1), at least from
      the standpoint of the effect POP/Tcf quality has on the control of cell polarity
      in C. elegans.

PMID- 14977565
TI  - Adeno-associated viral vector-mediated ApoE expression in Alzheimer's disease
      mice: low CNS immune response, long-term expression, and astrocyte specificity.
AB  - Recombinant Adenovirus and Adeno-associated virus (AAV) are highly effective
      vehicles for gene transfer into CNS cells. However, the duration of gene
      expression and the cytotoxicity to cells are quite different between these viral
      approaches. We initially investigated these distinctions by stereotaxically
      injecting both Adenovirus vector and AAV vectors expressing reporter genes into
      mouse hippocampus. The adenovirus vector induced a pronounced immune response
      with a marked increase in CD45 and MHC class I protein expression and transgene
      expression was shorter than six weeks. In contrast, with the AAV vector there was
      lower expression of CD45 and MHC class I immune activation markers, and longer
      expression of reporter gene (up to 12 months). To study the roles of human
      Apolipoprotein E (ApoE) alleles in the pathogenesis of Alzheimer's disease and
      other CNS diseases, we generated recombinant AAV-apoE alleles driven by the GFAP
      promoter and expressed them in the mouse brain of Alzheimer's disease mouse. High
      level ApoE expressions in mouse brain lasted for 12 months, and ApoE was
      specifically expressed in astrocytes. We demonstrate that AAV-GFAP-ApoE is
      valuable in studying the pathogenesis and in gene therapy for Alzheimer's disease
      and other CNS diseases.

PMID- 14977566
TI  - Abnormal levels of interferon-gamma receptors in active multiple sclerosis are
      normalized by IFN-beta therapy: implications for control of apoptosis.
AB  - Interferon-gamma is produced by immune cells before MS exacerbations, and
      exogenous IFN-gamma treatment causes MS attacks. IFN-beta production, conversely,
      rises after exacerbations. IFN-beta therapy ameliorates MS, possibly by lowering
      IFN-gamma secretion and inhibiting responses to IFN-gamma. IFN-gamma effects are
      regulated by IFN-gamma receptor (IFNGR) expression. IFN-gamma is pro-inflammatory
      at low IFNGR levels, but induces apoptosis in cells with high IFNGR levels. We
      studied effects of IFN-beta1a therapy on IFNGR expression on PMA/ionomycin
      stimulated PBMNC's in 29 patients with active and stable MS. Surface IFNGR-alpha
      (the binding chain) and IFNGR-beta (signaling chain), as well as intracellular
      IFN-gamma and IL-10, were measured with flow cytometry. Before IFN-beta therapy,
      intracellular IL-10 was depressed and the IFN-gamma/IL-10 ratio was elevated in
      MS, particularly during clinical activity. With IFN-beta therapy IL-10 levels
      increased, suggesting that a Th2 deficit was reversed. The IFNGR-alpha chain was
      significantly elevated on lymphocytes in stable and active MS patients not
      receiving IFN-beta therapy. Expression of the IFNGR-beta chain was low during
      active untreated disease. After IFN-beta therapy, the IFNGR-beta/alpha ratio
      increased at 3 months and fell at 12 months. Increased susceptibility to
      apoptosis with high IFNGR-beta chain expression at 3 months is likely to remove
      activated T cells during IFN-beta therapy.

PMID- 14977567
TI  - Atomic resolution structures and the mechanism of ion pumping in
      bacteriorhodopsin.
AB  - A structure-based approach to the mechanism of ion pumping in bacteriorhodopsin
      (BR) has fostered new hypotheses for the detailed molecular changes that underlie
      ion transport in this light-driven pump. Isomerization of the retinal from all
      trans to 13-cis in response to absorption of the energy of a photon is thought to
      lead to proton transfer from the initially protonated Schiff base to an anionic
      aspartate residue (Asp85) in the first half of the BR photocycle. In this
      traditional view the proton is transferred directly from the Schiff base to
      Asp85. A comparison of structures of photocycle intermediates trapped shortly
      after proton transfer to Asp85 to those of the resting state suggested an
      alternative view for the mechanism of proton transfer. In this scenario, a local
      water molecule in hydrogen bond contact with the Schiff base and Asp85 in the
      resting state is destabilized upon isomerization of the retinal. The destabilized
      water loses a proton to Asp85 and the remaining hydroxyl anion migrates toward
      the positively charged Schiff base to abstract its proton. This mechanism, in
      which a hydroxyl ion is pumped in lieu of a proton, has now been challenged by
      interpretations of new structures for photointermediates that immediately precede
      and follow the deprotonation/protonation reaction. However, in contrast to the
      older structures in which photointermediates were prepared at room temperature,
      the new structures were obtained by illuminating wild-type BR in frozen crystals.
      The results of spectroscopic studies of BR suggest that the structures of
      intermediates trapped at low temperature may not be the same as native photocycle
      intermediates at room temperature. The precise mechanism of ion transfer in BR is
      therefore unresolved.

PMID- 14977568
TI  - Apoptosis in acute and chronic neurological disorders.
AB  - Programmed cell death or apoptosis is a physiologically important process in
      neurogenesis wherein approximately 50% of the neurons apoptose during maturation
      of the nervous system. However, premature apoptosis and/or aberrations in
      apoptosis control contribute to the pathogenesis of a variety of neurological
      disorders including acute brain injury such as trauma, spinal cord injury,
      ischemic stroke and ischemia/reperfusion as well as chronic disease states such
      as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, spinal
      muscular atrophy, and diabetic neuropathy. The current review will focus on two
      major topics, namely, the general concepts of our current understanding of the
      apoptosis death machinery, its mediators and regulation, and the relationship
      between aberrant apoptosis and genesis of neurodegenerative disorders. This
      knowledge of apoptosis mechanisms will underpin the basis for development of
      novel therapeutic strategies and treatment modalities that are directed at
      control of the neuronal apoptotic death program.

PMID- 14977569
TI  - Molecular biology of pyridine nucleotide and nicotine biosynthesis.
AB  - Nicotinamide adenine dinucleotide (NAD) is a ubiquitous coenzyme in oxidation
      reduction reactions. Recent animal and fungal studies show that it also plays
      important roles in transcriptional regulation, longevity, and age-associated
      diseases. NAD is synthesized de novo from aspartic acid in E. coli or from
      tryptophan in animals, by way of quinolinic acid. Although the number of
      biochemical studies on NAD is very limited, a bioinformatic search of genome
      databases suggests that Arabidopsis (dicots) synthesizes NAD from aspartic acid
      whereas rice (monocots) may utilize both aspartate and tryptophan as starting
      amino acids. The salvage pathway recycles the breakdown products of NAD
      metabolism. In tobacco, an intermediate in the de novo NAD synthetic pathway
      supplies the pyridine ring moiety of nicotine alkaloids. Gene expression studies
      in tobacco suggest that part of the NAD pathway is coordinately regulated with
      nicotine biosynthesis.

PMID- 14977570
TI  - Redundancy or flexibility: molecular diversity of the electron transfer
      components for P450 monooxygenases in higher plants.
AB  - Specific metabolic roles of P450-dependent monooxygenase systems are determined
      by enzymatic properties and substrate specificity of P450s, the terminal enzymes
      of the electron transfer chain. On the other hand, molecular diversity has also
      been reported for NADPH-cytochrome P450 reductase, cytochrome b5, and cytochrome
      b5 reductase in plants. Several lines of evidence indicate that the electron
      transfer components for plant P450 reactions have specific physiological roles.
      In this review, we describe the current status of knowledge of the biochemistry,
      molecular biology, gene regulation, and molecular diversity of plant P450-related
      electron transfer components and summarize possible individual physiological
      roles of the diversified P450 electron transfer systems in plants.

PMID- 14977571
TI  - Applications of multi-photon microscopy in cell physiology.
AB  - Owing to its many optical and physical advantages for fluorescence excitation,
      multi-photon microscopy has found a wide range of uses in biology, both in
      structural and functional studies. In this review we highlight various
      applications of this technique in different fields of cell physiology and
      biophysical research. This includes studies on second messenger and ionic
      signals, on cellular metabolism as well as on genetically engineered probes and
      indicators. In addition, this techniques has been successfully applied for
      diffraction-limited photolysis of caged compounds. We also point out some of the
      problems that were encountered along the still rapidly evolving path of this
      technique, and draw attention to some of the ongoing developments that will
      further extend and improve the usefulness of multi-photon excitation, such as
      fluoresce life-time imaging (FLIM), fluorescence resonance energy transfer (FRET)
      and entangled photon microscopy approaches.

PMID- 14977572
TI  - Regulation of pyrimidine metabolism in plants.
AB  - Pyrimidine nucleotides represent one of the most fundamental of cellular
      components. They are the building blocks for the direct synthesis of DNA and RNA
      that function in information storage and retrieval within the cell, but they also
      participate in the metabolism of a large number of other cellular components from
      sugar interconversion to cellular polysaccharides to glycoproteins and
      phospholipids. Thus, the metabolism of pyrimidine nucleotides and their
      intracellular pool sizes influence vast areas of normal cellular metabolism. The
      first pyrimidine, UMP, is synthesized by a de novo pathway that appears to be
      mechanistically invariant in all organisms. UMP is then further modified to form
      other pyrimidines. Breakdown of deoxyribo- and ribonucleic acids, the main sink
      for pyrimidine nucleotides, allows pyrimidines to be reutilized for resynthesis
      of these important cellular components. Pyrimidines are salvaged by converting
      the modified components into the free base, uracil for reutilization. Finally,
      pyrimidines are degraded into simple cellular metabolites permitting
      reutilization of nitrogen and carbon from pyrimidine ring systems into cellular
      metabolic pools. The regulation of pyrimidine metabolism is tightly controlled in
      plants. Additionally, plants produce toxic secondary metabolites derived from
      pyrimidines for use as defense compounds.

PMID- 14977573
TI  - Regulation and functional roles of Grb14.
AB  - Grb14 is the last described member of the Grb7 family of adaptors, containing
      Grb7, Grb10 and Grb14. These proteins share a series of conserved domains
      involved in protein-protein and protein-lipid interactions: an amino terminal
      proline-rich region, a C-terminal SH2 domain, and a central GM region containing
      a RA, a PH domain, and a newly described PIR (BPS) region. As shown for the other
      members of the Grb7/10/14 family, Grb14 binds to various receptor tyrosine
      kinases (RTKs) under ligand induction. This interaction involves the SH2 and PIR
      domains, and the respective participation of these domains is likely to be a
      determinant in the specificity of action of Grb14. At the present time, a role
      for this Grb14-RTK interaction was established only for insulin (IR) and FGF
      receptors (FGFR). Grb14, through its PIR, is an inhibitor of IR tyrosine kinase
      activity and thus of insulin effects. Grb14 also decreases FGF signaling, but
      more probably by interfering with cellular effectors downstream from the
      receptor. Only a few cytosolic partners of Grb14 are identified. One of them, the
      adaptor ZIP, allows phosphorylation of Grb14, and regulation of its inhibitory
      action on IR signaling. The identification of further proteins interacting with
      Grb14 is required to elucidate the biological role of this protein.

PMID- 14977574
TI  - Sepsis associated encephalopathy (SAE): a review.
AB  - Sepsis associated encephalopathy (SAE) is a poorly understood condition that is
      associated with severe sepsis and appears to have a negative influence on
      survival. The incidence of encephalopathy secondary to sepsis is unknown. Amino
      acid derangements, blood-brain barrier disruption, abnormal neurotransmitters,
      and direct CNS effect are possible causes of septic encephalopathy. Research has
      not defined the pathogenesis of SAE.

PMID- 14977575
TI  - Rapidity and multiplicity of synthesis and expression of immunoglobulin isotypes
      by B lymphocytes in the small intestine.
AB  - An immunofluorescence double labeling assay was used to examine the kinetics of
      intestinal B lymphocytes with concurrent expression of multiple antibody isotypes
      in the mucosal tissues of rats infected with Trichinella spiralis (TS) muscle
      larvae for 1 to 15 days. As compared to the uninfected controls (day 0), the non
      Peyer's patch tissues of the small intestine contained a significantly increased
      number of dual antibody-expressing B cells as early as 3 days after infection
      with a maximum proliferation of these B cells on days 7 and 10. These results
      indicate the rapidity of B cell response in the small intestine. Similar results
      were observed in the germinal centers of the Peyer's patches. The non-germinal
      centers of the Peyer's patch tissues showed delayed kinetics in B cell activation
      which occurred 10 days after infection. Quantification of the total number of B
      cells in these tissues was also carried out by staining the CD45RA marker on B
      cells with the OX33 monoclonal antibody. When comparing the total numbers of B
      cells with the numbers of B cells expressing dual isotypes of antibodies, our
      results showed the numbers of dual-expressing B cells (IgA:IgE, IgM:IgE,
      IgG1:IgE, IgG2a:IgE, IgG2b:IgE, and IgG2c:IgE), when combined, were over 7 times
      that of the total number of OX33-labeled B cells on day 7 in the small intestine.
      The dual-expressing B cells in the Peyer's patch-germinal center were more than 5
      times that of the OX33-labeled B cells on day 15. These results therefore suggest
      that the dual-expressing B cells most likely synthesized and expressed more than
      two isotypes of antibodies during the peak days of the humoral response. Such
      phenomenon was not observed in non-germinal centers of the Peyer's patch tissues.

PMID- 14977576
TI  - Soluble adhesion molecule levels, neuropsychiatric lupus and lupus-related
      damage.
AB  - Nervous system dysfunction may occur in as many as 80% of patients with Systemic
      Lupus Erythematous (SLE) at some point in their disease course. Upregulation of
      adhesion molecules has been linked to acute SLE-related disease activity and
      chronic damage. We evaluated the relationship between soluble adhesion molecule
      levels and neuropsychiatric lupus (NPSLE) manifestations using the American
      College of Rheumatology (ACR) case definitions to investigate for evidence of a
      link between upregulation of adhesion molecules and NPSLE manifestations. Sera
      from the initial study visit of 133 SLE patients enrolled in the San Antonio
      Lupus Study of Neuropsychiatric Disease (SALUD) and 40 controls were evaluated
      for soluble adhesion molecule levels (VCAM-1, ICAM-1 and E-selectin) and
      antiphospholipid antibodies. A subset of 57 SLE patients were evaluated for
      soluble adhesion molecule levels and antiphospholipid antibodies on two
      subsequent study visits, as well. NPSLE manifestations at the time of sera
      ascertainment were recorded using ACR case definitions and SLE-related acute
      activity and damage were measured. Elevated levels of all three soluble adhesion
      molecules were seen in SLE patients compared to normal control values. Soluble
      VCAM-1 levels correlated with measures of current disease activity, NPSLE
      manifestations and deep venous thrombosis. Persistently positive levels of ICAM-1
      and VCAM-1, but not E-selectin were association with increased SLE-related
      damage. Elevated levels of all soluble adhesion molecule levels correlated with
      abnormal levels of antiphospholipid antibodies, which are associated with some
      NPSLE manifestations and have been shown to upregulate adhesion molecule
      expression.

PMID- 14977577
TI  - The serum growth hormone to somatostatin ratio is skewed upward in rheumatoid
      arthritis patients.
AB  - Basal serum growth hormone, insulin-like growth factor-1 (IGF-1) and somatostatin
      concentration were measured by standard radioimmunoassay in patients with a
      diagnosis of rheumatoid arthritis (RA) according to the criteria of the American
      College of Rheumatology as well as in a group of age-matched normal subjects. RA
      patients exhibited significantly elevated (age, 45-55 yrs, p less than 0.05; 55
      yrs and older, p less than 0.01) serum growth hormone levels compared to age
      matched individuals from the control group. IGF-1 was unchanged. Serum
      somatostatin levels were reduced in RA patients between 45 and 55 yrs but reached
      a significant reduction (p less than 0.0001) in RA patients, 55 years and older
      compared to age-matched individuals from the control group. RA patients treated
      with prednisone did not exhibit changes in either growth hormone or IGF-1 levels
      compared to RA patients treated principally with non-steroidal anti-inflammatory
      drugs and methotrexate. These results indicated that symptomatic RA is associated
      with elevated serum growth hormone without concomitant changes in IGF-1 compared
      to individuals from the control group. Reduced somatostatin levels in older RA
      patients resulted in a skewed upward growth hormone to somatostatin ratio. We
      conclude that the serum growth hormone to somatostatin ratio may be a useful
      surrogate marker of disease activity in symptomatic RA.

PMID- 14977579
TI  - Archaeal peptidyl prolyl cis-trans isomerases (PPIases) update 2004.
AB  - PPIases are ubiquitous in living organisms. While three families of PPIases,
      cyclophilin (CyP), FK506 binding protein (FKBP) and parvulin (Pvn), have been
      studied in detail in Eukarya and Bacteria (eubacteria), little is known about
      archaeal PPIases. Among 13 cyclophilins found in Archaea, only Halobacterium
      cyclophilin (HbsCyP19) has been characterized. This is a cyclosporin A (CsA)
      sensitive CyP with a molecular weight of 19.4 kDa. The PPIase activity and CsA
      sensitivity of HbsCyP19 is higher at higher salt concentration in the medium. No
      parvulin except a homolog in Cenarchaeum symbiosum has been found in Archaea. Two
      types of FKBPs, 26-30 kDa long-type and 17-18 kDa short-type FKBP, have been
      found in Archaea. Up to date, 12 short-type FKBPs and 18 long-type FKBPs have
      been known. The short-type FKBPs and N-terminal sequences of the long-type FKBPs
      are similar to each other and show homology to human FKBP12 (HsFKBP12). However,
      they have two insertion sequences in the regions corresponding to bulge and flap
      loops of HsFKBP12. The long-type archaeal FKBPs have additional ca. 100 amino
      acid sequences at their C-terminal regions. A short-type archaeal FKBP from
      Methanothermococcus thermolithotrophicus has not only a PPIase activity but also
      a chaperone-like activity, which includes protein refolding and aggregation
      suppressing activities with regard to protein folding intermediates. Mutational
      analysis revealed that this chaperone-like activity was independent of the PPIase
      activity, and that the insertion sequence in the region corresponding to the flap
      seemed to be important. Three-dimensional structure of this FKBP showed that the
      insertion in the flap makes a domain which has a hydrophobic surface.
      Coexpression of aggregation prone proteins with these archaeal FKBPs were shown
      to improve their expression in soluble fraction in Escherichia coli. Fusion
      protein of the archaeal FKBP and an aggregation prone protein also show improved
      expression of the latter in E. coli.

PMID- 14977580
TI  - Immunotherapy with Mycobacterium vaccae in the treatment of tuberculosis.
AB  - All the trials of immunotherapy of tuberculosis with killed Mycobacterium vaccae,
      published or not, that are known to the authors are reviewed here. Following an
      introduction giving a brief account of some earlier immunotherapies for
      tuberculosis, the origins of the concept of immunotherapy with M.vaccae are
      considered. Progress is traced from the early work with irradiation-killed
      organisms in leprosy to the study in London of modulation of tuberculin skin-test
      responses, and the first comparative trials in The Gambia and Kuwait. In the last
      of these studies, dosages and different preparations were compared. As a result
      of this subsequent studies have used 109 heat-killed organisms, equivalent to 1mg
      wet-weight of bacilli, as a standard dose. A series of small trials in Argentina,
      India, Nigeria, Romania, South Africa and Vietnam have pioneered the way forward,
      disclosing geographic variability, with South Africa as the only country where
      almost no effects were recorded. Together the studies have shown that a single
      dose may not be sufficient. These studies have confirmed the mode of action of
      M.vaccae to be regulation of cell-mediated immunity with enhancement of Th1 and
      down-regulation of Th2, and they have shown benefits in faster bacteriological
      conversion, reduction in ESR, recovery of body weight and resolution of
      radiological opacities, leading to better recovery from the disease even when
      given to patients receiving directly observed therapy, short-course (DOTS). Three
      major randomised, placebo-controlled and partly blinded trials have been carried
      out in Africa. The first, in South Africa showed no M.vaccae-related effects. The
      second trial, in Uganda, confirmed the observations made in the earlier studies
      of faster sputum conversion and better radiological clearance. The third trial,
      in Zambia and Malawi, showed a trend towards benefits in the treatment of HIV
      seronegative patients but failed to show beneficial effects in HIV seropositive
      patients. Studies in patients with multi-drug-resistant tuberculosis have shown
      that multiple doses of immunotherapy are required in most cases, and that these
      markedly improve cure-rates for these patients. This is especially so when they
      are also treated with chemotherapy tailored to the resistance pattern of their
      infecting organisms. A small study has just commenced in which repeated doses of
      M.vaccae are being administered to a group of patients who have failed treatment
      with DOTS-Plus (directly observed therapy with drugs selected on the basis of
      drug susceptibility profiles). Late in the investigation came publications from
      China supporting and confirming the data in both drug-sensitive and drug
      resistant disease, by the use of multiple injections of their own different
      preparation of M.vaccae. The trial that is now beginning in Vietnam of 3 doses of
      M.vaccae in the treatment of newly diagnosed pulmonary tuberculosis, is
      accompanied by a chemotherapeutic regimen with a shortened continuation phase. If
      this important study is successful, immunotherapy with killed M.vaccae should be
      introduced into the treatment regimens for tuberculosis worldwide.

PMID- 14977578
TI  - Post-transcriptional regulation of opioid receptors in the nervous system.
AB  - Three types of opioid receptors exist in the animals, each is encoded by a single
      gene, i.e., the mu opioid receptor gene, the delta opioid receptor gene, and the
      kappa opioid receptor gene. However, each opioid receptor gene produces multiple
      mRNA variants as a result of alternative promoter usages, splicing and/or
      polyadenylation. As such, a large reservoir of regulatory events has evolved for
      the control of the production of mRNA variants or differentially modified
      proteins from each opioid receptor gene. This review focuses on post
      transcriptional events for the regulation of opioid receptor expression or
      activities, including alternative splicing, mRNA stability, translation, RNA
      polyadenylation, RNA transport, and covalent modification of the receptors.
      Variation at the mRNA level contributes, primarily, to the control of spatial and
      temporal expression of these receptors in different parts of neurons; whereas
      modification at the receptors is the key for controlling the duration and
      amplitude of signals generated from these receptors.

PMID- 14977581
TI  - Antisense therapeutics and the treatment of CNS disease.
AB  - Antisense oligonucleotides (ONs) have great therapeutic potential for conditions
      in which aberrant protein production results in pathology. This method of
      reducing the expression of a target gene is both precise and sequence-specific.
      Although there are many applications for antisense ONs as central nervous system
      (CNS) therapeutics, systemically administered antisense ONs must be capable of
      crossing the blood-brain barrier (BBB) in quantities effective enough to alter
      protein production in the CNS. Because antisense ONs are large, highly polar
      molecules, their rate of transport across the BBB is likely to be low. Recent
      studies have shown that antisense ONs are capable of crossing the BBB without the
      aid of a carrier system, however little is known about the molecular mechanisms
      which mediate this transport. This review will focus on nucleic acid chemistries
      suitable for in vivo research and their potential applications in the treatment
      of CNS disease.

PMID- 14977582
TI  - Lipoprotein-matrix interactions in macrovascular disease in diabetes.
AB  - The retention of atherogenic lipoproteins in the artery wall through their
      interactions with the arterial extracellular matrix is a critical step in the
      development of atherosclerosis, as outlined in the 'response to retention'
      hypothesis. Lipoprotein retention by vascular proteoglycans is thought to be the
      principle means of lipoprotein retention, although lipoprotein binding to other
      components of the extracellular matrix has been reported. The interactions of
      lipoproteins and proteoglycans can be direct through ionic interactions between
      the negatively charged glycosaminoglycan chains of proteoglycans and positively
      charged residues of apolipoproteins B and E, or can be mediated through bridging
      molecules such as lipoprotein lipase. Retention of atherogenic lipoproteins
      within the artery wall environment leads to pathophysiologically important
      modifications of the lipoproteins, including oxidation. Oxidation of lipoproteins
      leads to increased uptake by macrophages, leading to the formation of foam cells.
      This article reviews the scientific evidence in support of the response to
      retention hypothesis, with a specific focus on the effects of diabetes to modify
      lipoprotein retention.

PMID- 14977583
TI  - Proteasomes: perspectives from the Archaea.
AB  - The development of whole systems approaches to microbiology (e.g. genomics and
      proteomics) has facilitated a global view of archaeal physiology. Surprisingly,
      as archaea respond to environmental signals, the majority of protein
      concentration changes that occur are not reflected at the mRNA level. This
      incongruity highlights the importance of post-transcription control mechanisms in
      these organisms. One of the central players in proteolysis is the proteasome, a
      multicatalytic energy-dependent protease. Proteasomes serve both proteolytic and
      non-proteolytic roles in protein quality control and in the regulation of cell
      function. The proteolytic active sites of these enzymes are housed within a
      central chamber of an elaborate nanocompartment termed the 20S proteasome or core
      particle. Axial gates, positioned at each end of this particle, restrict the type
      of substrate that can access the proteolytic active sites. Assortments of
      regulatory AAA complexes are predicted to recognize/bind and unfold substrate
      proteins, open the axial gates, and translocate substrate into the 20S core
      particle.

PMID- 14977584
TI  - Polyoxometalates: from inorganic chemistry to materials science.
AB  - Polyoxometalates have been traditionally the subject of study of molecular
      inorganic chemistry. Yet, these polynuclear molecules, reminiscent of oxide
      clusters, present a wide range of structures and with them ideal frameworks for
      the deployment of a plethora of useful magnetic, electroionic, catalytic,
      bioactive and photochemical properties. With this in mind, a new trend towards
      the application of these remarkable species in materials science is beginning to
      develop. In this review we analyze this trend and discuss two main lines of
      thought for the application of polyoxometalates as materials. On the one hand,
      there is their use as clusters with inherently useful properties on themselves, a
      line which has produced fundamental studies of their magnetic, electronic or
      photoelectrochemical properties and has shown these clusters as models for
      quantum-sized oxides. On the other hand, the encapsulation or integration of
      polyoxometalates into organic, polymeric or inorganic matrices or substrates
      opens a whole new field within the area of hybrid materials for harnessing the
      multifunctional properties of these versatile species in a wide variety of
      applications, ranging from catalysis to energy storage to biomedicine.

PMID- 14977585
TI  - Applying high throughput techniques in the study of adenosine kinase in plant
      metabolism and development.
AB  - Adenosine kinase (ADK, EC 2.7.1.20) is a purine salvage enzyme, which
      phosphorylates adenosine (Ado) to AMP. It may also contribute to the
      interconversion of cytokinin ribosides and nucleotides. Recent microarray
      analyses have provided new insights into the impact of ADK activity towards plant
      metabolism and development. The majority of these findings reflect ADK's role in
      the metabolism of Ado produced from transmethylation reactions in addition to
      providing necessary nucleotides for the synthesis of nucleic acids and nucleotide
      cofactors. As such, ADK was found to increase during events associated with high
      transmethylation activity, such as cell wall synthesis and seed filling.
      Differences between plant organs were also detected, with ADK transcript levels
      found highest in siliques and roots and lowest in callus, leaves and buds.
      Transcript profiling of Arabidopsis expression using microarrays, reveals a
      predominance of ADK1 expression relative to that of ADK2. In the majority of the
      studies, the isoforms appeared to behave in a similar pattern of expression, with
      the exception being microgametogenesis where ADK1 was up-regulated when ADK2 was
      not. What specialized function the ADK1 could be providing to these cells during
      development and whether or not this is occurring in other biochemical processes
      has yet to be determined.

PMID- 14977586
TI  - Tachykinins in the emerging immune system: relevance to bone marrow homeostasis
      and maintenance of hematopoietic stem cells.
AB  - The mammalian tachykinins mediate crosstalk within the neural-immune
      hematopoietic axis. Hematopoiesis occurs in the adult bone marrow (BM) and it is
      described as the method by which the immune system is replenished by a finite
      number of hematopoietic stem cells (HSC). These cells are found in the BM close
      to the endosteum where the oxygen level is the lowest. The BM is also resident to
      mesenchymal stem cell (MSC). The functions of HSC depend on the MSC to generate
      the supporting stromal cells. This review discusses possible mechanisms by which
      the MSC act as the 'gatekeeper' in the BM and regulate immune cells in and out of
      the BM. The roles of the tachykinins are discussed in the context of homeostasis
      in the BM and as mediators of BM disruption. The involvement of the tachykinins
      within the BM microenvironment and the development of immune cells in the BM are
      explained.

PMID- 14977587
TI  - Extracellular virulence factors of group B Streptococci.
AB  - Group B Streptococcus (GBS) is the leading cause of severe bacterial infections
      in human newborn infants. Advances in streptococcal molecular genetics and
      refinement of in vitro and in vivo model systems of GBS disease have led to the
      discovery and characterization of several extracellular virulence factors
      elaborated by this pathogen. This review summarizes our current understanding of
      GBS extracellular virulence factors including the beta-hemolysin/cytolysin, C5a
      peptidase, hyaluronate lyase, CAMP factor, oligopeptidase, and carbohydrate
      exotoxin CM101. The molecular basis and potential pathogenic role(s) of each
      factor are considered in the context of neonatal infection.

PMID- 14977588
TI  - Molecular analysis of "de novo" purine biosynthesis in solanaceous species and in
      Arabidopsis thaliana.
AB  - Purine nucleotides are essential components to sustain plant growth and
      development. In plants they are either synthesized "de novo" during the process
      of purine biosynthesis or are recycled from purine bases and purine nucleosides
      throughout the salvage pathway. Comparison between animals, microorganisms and
      Arabidopsis, the first plant species with a completely sequenced genome, shows
      that plants principally use the same biochemical steps to synthesize purine
      nucleotides and possess all the essential genes and enzymes. Here we report on
      the cloning and molecular analysis of the complete purine biosynthesis pathway in
      plants, and the in planta functional analysis of PRPP (5-phosphoribosyl-1
      pyrophoshate) amidotransferase (ATase), catalyzing the first committed step of
      the "de novo" purine biosynthesis. The cloning of the genes involved in the
      purine biosynthesis pathway was attained by a screening strategy with
      heterologous cDNA probes and by using S. cerevisiae mutants for complementation.
      Southern hybridization showed a complex genomic organization for these genes in
      solanaceous species and their organ- and developmental specific expression was
      analyzed by Northern hybridization. The specific role of ATase for plant growth
      and development was analyzed in transgenic tobacco plants exhibiting a reduced
      ATase activity and in an Arabidopsis T-DNA mutant (atd2) deficient for ATase2.
      The transgenic tobacco plants as well as the Arabidopsis mutant exhibit a
      specific and comparable phenotype, which is characterized by strong growth
      retardation and severe chlorosis in leaves. The formation of white leaves, but
      green cotyledons is a characteristic trait of the Arabidopsis atd2 mutant.

PMID- 14977589
TI  - ALG-2, a multifunctional calcium binding protein?
AB  - ALG-2 was originally discovered as a pro-apoptotic protein in a genetic screen.
      Due to its ability to bind calcium with high affinity it was postulated to
      provide a link between the known effect of calcium in programmed cell death and
      the molecular death execution machinery. This review article discusses the
      current knowledge on the structure and potential function of this protein.
      Several putative binding partners of ALG-2 have been identified hinting to
      functions of ALG-2 in apoptosis and possibly also in proliferation, endocytosis
      and transcriptional regulation during development. Gene deletion of the well
      conserved ALG-2 locus in several genetic model organisms has so far not provided
      insights into functions and signaling pathways with ALG-2 involvement. Special
      focus is given to controversial data on expression and localization of ALG-2,
      which is mainly caused by the use of ALG-2 antibodies with different
      specificities.

PMID- 14977590
TI  - Caffeine synthase and related methyltransferases in plants.
AB  - Caffeine (1,3,7-trimethylxanthine) is a purine alkaloid present in high
      concentrations in tea and coffee and it is also found in a number of beverages
      such as coca cola. It is necessary to elucidate the caffeine biosynthetic pathway
      and to clone the genes related to the production of caffeine not only to
      determine the metabolism of the purine alkaloid but also to control the content
      of caffeine in tea and coffee. The available data support the operation of a
      xanthosine-->7-methylxanthosine-->7-methylxanthine-->theobromine-->caffeine
      pathway as the major route to caffeine. Since the caffeine biosynthetic pathway
      contains three S-adenosyl-L-methionine (SAM) dependent methylation steps, N
      methyltransferases play important roles. This review focuses on the enzymes and
      genes involved in the methylation of purine ring. Caffeine synthase, the SAM
      dependent methyltransferase involved in the last two steps of caffeine
      biosynthesis, was originally purified from young tea leaves (Camellia sinensis).
      The isolated cDNA, termed TCS1, consists of 1,483 base pairs and encodes a
      protein of 369 amino acids. Subsequently, the homologous genes that encode
      caffeine biosynthetic enzymes from coffee (Coffea arabica) were isolated. The
      recombinant proteins are classified into the three types on the basis of their
      substrate specificity i.e. 7-methylxanthosine synthase, theobromine synthase and
      caffeine synthase. The predicted amino acid sequences of caffeine biosynthetic
      enzymes derived from C. arabica exhibit more than 80% homology with those of the
      clones and but show only 40% homology with TCS1 derived from C. sinensis. In
      addition, they share 40% homology with the amino acid sequences of salicylic
      carboxyl methyltransferase, benzoic acid carboxyl methyltransferase and jasmonic
      acid carboxyl methyltransferase which belong to a family of motif B'
      methyltransferases which are novel plant methyltransferases with motif B' instead
      of motif B as the conserved region.

PMID- 14977591
TI  - Fluorometric evidence for different stoichiometries for the Na+/Mg2+ exchange in
      Mg-loaded rat thymocytes.
AB  - The regulation of the cytosolic free magnesium concentration ([Mg2+]i) is a
      fundamental cellular process that requires magnesium extruding mechanisms. Here,
      we present evidence indicating that rat thymocytes are endowed with different
      Na/Mg exchange systems. Fluxes of magnesium were measured using the fluorescent
      magnesium indicator magfura-2. Cells were loaded with magnesium using the calcium
      ionophore A-23187 to 0.6-8.0 mM [Mg2+]i (resting [Mg2+]i = 0.38 +/- 0.06 mM, n =
      5). The presence of extracellular sodium was required for magnesium exit. The
      initial rate of [Mg2+]i was stimulated by extracellular sodium with Michaelis
      Menten kinetics. The Vmax of the sodium-dependent magnesium exit was markedly
      increased by [Mg2+]i. Holding the membrane potential at either -84 mV or at -10
      mV had different effects on the sodium-stimulated magnesium efflux, depending on
      the extracellular sodium concentration ([Na+]o). At 10-30 mM [Na+]o, the
      magnesium efflux was faster at -10 mV than at -84 mV. Conversely, at 50-200 mM
      [Na+]o, the efflux of magnesium was faster at -84 mV that at -10 mV. At 75 mM
      [Na+]o, the activities where nearly the same at both membrane potential values.
      These observations suggest that the stochiometry of the Na+/Mg2+ exchange changes
      with [Na+]o.

PMID- 14977592
TI  - Interactive protrusive structures during leukocyte adhesion and transendothelial
      migration.
AB  - Leukocyte transendothelial migration during homing and inflammation requires
      drastic cell morphological changes, involving cytoskeletal-directed clustering of
      adhesion receptors in specialized protrusive membrane structures in leukocytes
      and endothelial cells. Extravasation is an active process not only for leukocytes
      but also for endothelial cells, which promote the rapid and efficient entry of
      leukocytes to the target tissues, without disturbing the integrity of the
      endothelial barrier. Herein, we have revised the specialized protrusive
      structures (microvilli, endothelial docking structures, leukocyte lamellipodia
      and uropod) involved in the different stages of leukocyte extravasation. The
      adhesion receptor redistribution, cytoskeletal remodelling and intracellular
      signaling events that participate in this phenomenon are also discussed.

PMID- 14977593
TI  - Distribution and biosynthesis of caffeine in plants.
AB  - Methylxanthines and methyluric acids are secondary metabolites derived from
      purine nucleotides and are known collectively as purine alkaloids. The present
      review begins by summarizing the distribution of these compounds in the plant
      kingdom, and then provides an up-to-date account of the biosynthesis of purine
      alkaloids. The diversity of biosynthesis and accumulation between species and
      between tissues of different age is considered. We also discuss the physiological
      function of these purine alkaloids in plants and the biotechnology for creating
      caffeine-free plants.

PMID- 14977594
TI  - Hypothermia in systemic inflammation: role of cytokines.
AB  - Hypothermia is a thermoregulatory response to systemic inflammation that is often
      regarded as maladaptive to the host. However, rodents show regulated hypothermia
      (that is, a selection of cool ambient temperature) during systemic inflammation
      that correlates with enhanced survival, supporting an adaptive value to this
      response. The mechanisms regulating hypothermia are not fully understood, but
      cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukins (ILs) and
      interferon-gamma have been shown to induce or modulate hypothermia. A review of
      the literature suggests that TNF-alpha functions as an endogenous cryogen (i.e.,
      induces hypothermia), whereas IL-10 modulates TNF-alpha production and/or release
      as a mechanism of hypothermia attenuation. IL-1beta and IL-6 are typically
      regarded as endogenous pyrogens, but may induce hypothermia during viral and
      bacterial inflammation. A role for endogenous IFN-gamma in hypothermia has not
      been demonstrated, but injection of this cytokine potentiates hypothermia through
      augmented production of other cytokines. It is clear that additional research is
      required in this area. Suggested areas for future research include a
      determination of the final mediator of hypothermia and its specific anatomical
      site of action as well as the role of cytokines in the regulation of hypothermia
      under non-inflammatory conditions.

PMID- 14977595
TI  - Alterations of cell signaling pathways in pancreatic cancer.
AB  - Pancreatic ductal adenocarcinomas continue to have the worst prognosis of any
      adult malignancy with a five-year survival rate of less than 4%. One approach to
      improve patient survival from pancreatic cancer is to identify new biological
      targets that contribute to the aggressive pathogenecity of this disease and to
      develop reagents that will interfere with the function of these targets. Apart
      from the identification of the genetic profile of pancreatic cancer, a number of
      studies have focused on aberrant cell signaling pathways and their role in
      pancreatic cancer biology and response to therapy. This review, although not
      comprehensive, will discuss the salient features of several of these pathways.
      These include the roles of TGF beta signaling in both tumor suppression and tumor
      promotion and the effects of deregulation of phosphotyrosine kinase receptor
      signaling pathways in pancreatic cancer.

PMID- 14977596
TI  - Cognitive function and its neural mechanisms in nonhuman primate models of aging,
      Alzheimer disease, and menopause.
AB  - Nonhuman primates have been used as animal models in which to study cognitive
      changes associated with aging and age-related disease for decades. There are many
      advantages to using nonhuman primates for studies of aging including the
      capability to examine visual nonspatial cognitive processes and the ability to
      use operationally similar behavioral tasks to what is used with humans. Because
      some aspects of aging in humans do not develop naturally in nonhuman primates or
      do not follow the same course of natural development in monkeys, experimental
      models are necessary for some investigations. Research in our laboratory has
      identified similarities in the cognitive profiles of nonhuman primate models of
      aging, Alzheimer Disease, and menopause with their human counterparts. In
      addition, through the use of a variety of different techniques we have used these
      nonhuman primate models to begin to determine the neural substrates of age
      related cognitive dysfunction noted with advanced age and age-related disease. In
      this paper, we review our observations made in nonhuman primate models of aging,
      Alzheimer Disease, and menopause and indicate areas for future research.

PMID- 14977597
TI  - In vivo engineering of blood vessels.
AB  - The inadequacy of conventional synthetic grafts has led to efforts to construct a
      superior vascular graft. In vivo tissue engineering is one approach to this
      problem that has been investigated for half a century and enables the
      construction of autogenous vascular prostheses. Three types of in vivo
      engineering are explored: remodelling of implanted scaffolds, fibrocollagenous
      tubes, and the artificial artery generated in the peritoneal cavity. Scaffolds
      designed to be remodelled may be synthetic or biological and have been remodelled
      in animal models to form vasoactive neoarteries with arterial morphology. The
      differences in vascular remodelling ability, particularly spontaneous
      endothelialisation, between animal models and humans may impair the effectiveness
      of this approach in the clinic. Fibrocollagenous tubes such as the Sparks Mandril
      have demonstrated poor performance in the clinic and are prone to aneurysm
      formation. The artificial artery generated in the peritoneal cavity is a novel
      addition to the ranks of in vivo engineered vascular prostheses and combines many
      of the best features of scaffolds designed to be remodelled and fibrocollagenous
      tubes. However, understanding and manipulating the vascular remodelling process
      will be the key to producing the ideal arterial prosthesis.

PMID- 14977598
TI  - Tumor-suppressive and promoting function of transforming growth factor beta.
AB  - Transforming growth factor beta (TGFbeta) is a multifunctional polypeptide. Its
      role in carcinogenesis can be either suppressive or promoting depending on tumor
      developmental stages and cellular context. During the early phase of epithelial
      tumorigenesis, TGFbeta inhibits primary tumor development and growth by inducing
      cell cycle arrest and possibly apoptosis. However, in late stages of progression,
      as tumor cells evade the growth inhibition by TGFbeta due to inactivation of its
      signaling pathway or aberrant regulation of cell cycle machinery, the role of
      TGFbeta signaling is often switched from tumor suppression to promotion. TGFbeta
      can apparently act in tumor stroma as well as tumor cells to inhibit host immune
      surveillance and stimulate invasion, angiogenesis, and metastasis. Studies have
      shown that antagonizing TGFbeta activity can inhibit tumor progression,
      especially metastasis, in certain tumor models. However, the molecular markers
      that can indicate the feasibility of the use of TGFbeta antagonists as cancer
      therapeutics remain to be determined.

PMID- 14977599
TI  - The role of substance P, hemokinin and their receptor in governing mucosal
      inflammation and granulomatous responses.
AB  - Granulomas are chronic inflammations that prevent spread of poorly controllable
      infectious agents. The gut lumen contains enteric organisms that are excluded
      from the host by leukocytes located in the intestinal lining. Physiological
      intestinal inflammation and granulomas share some similarities. Both function to
      confine, but not necessarily abolish potentially harmful factors. Also, both are
      subject to intense immune regulation to avoid unnecessary tissue injury.
      Substance P and its natural analog hemokinin are produced at these sites of
      inflammation and are important components of this regulatory process. They act
      through a shared receptor (NK-1) expressed on T cells, macrophages, dendritic
      cells and probably other cell types. One of their functions is to enhance IFN
      gamma production and amplify the Th1 response. The NK-1 receptor is an important
      target for immune regulation. Several Th1 cytokines and T cell antigen receptor
      (TCR) activation induce NK-1 receptor expression on T cells, while IL-10 and TGF
      beta block receptor display. Macrophages also have an inducible NK-1 receptor.
      Various types of immune cells can make substance P and hemokinin, whose syntheses
      also are subject to immunoregulation. Thus, substance P and hemokinin are
      inflammatory cytokines with overlapping functions that help control immune
      responses in granulomas and at mucosal surfaces, and probably elsewhere.

PMID- 14977600
TI  - The role of dynamin in the assembly and function of podosomes and invadopodia.
AB  - Cells make contact with the extracellular matrix (ECM) through extensions of the
      plasma membrane; these range from irregular dynamic structures, e.g.
      lamellipodia, ruffles and pseudopodia, to more localized and highly defined
      protrusions, e.g. podosomes and invadopodia. Both might be instruments through
      which cells sample the immediate extracellular environment and maintain polarized
      activities such as chemotaxis and focal degradation of the matrix. Podosomes are
      expressed in cells of the monocytic lineage, and most studies point to a role for
      podosomes in adhesion/motility. Invadopodia are prominent in certain aggressive
      cancer cells (or transformed cells) and appear to be directly responsible for
      focal ECM degradation. Recent studies have revived interest in these structures
      in terms of the actin regulation machinery. Within this framework, the atypical
      GTP-binding protein dynamin, a central modulator of protrusive events, has been
      associated to podosome and invadopodia structure and function. Here, we
      specifically discuss the role played by dynamin in controlling the activities and
      function of these structures.

PMID- 14977601
TI  - Regulation of cell surface expression of voltage-dependent Nav1.7 sodium
      channels: mRNA stability and posttranscriptional control in adrenal chromaffin
      cells.
AB  - Regulated expression of Na+ channels is indispensable to physiological events,
      whereas dysregulated expression of otherwise silent or even normal Na+ channel
      isoforms causes Na+ channelopathies; however, the regulatory mechanisms remain
      unknown. In quiescent cultured bovine adrenal chromaffin cells, constitutive
      phosphorylation/activation of extracellular signal-regulated kinase-1 (ERK1) and
      ERK2 destabilized Nav l.7 Na+ channel alpha-subunit mRNA and decreased its level
      without altering alpha-subunit gene transcription, thus negatively regulating
      steady-state level of Na+ channels. Activation of protein kinase C (PKC) down
      regulated Na+ channels via PKC isoform-specific mechanisms; conventional PKC
      alpha promoted endocytic internalization of Na+ channels, whereas novel PKC
      epsilon destabilized alpha-subunit mRNA without altering its gene transcription.
      Long-lasting (but not short-term) increase of cytoplasmic Ca2+ down-regulated Na+
      channels; a slowly-developing moderate increase of Ca2+ activated PKC-alpha and
      calpain, promoting internalization of Na+ channels, whereas an immediate
      monophasic and salient plateau increase of Ca2+ lowered alpha- and beta1-subunit
      mRNA levels. Calcineurin, or FK506 binding protein- and rapamycin-associated
      protein (FRAP), a serine/threonine protein kinase, down-regulated, whereas
      insulin receptor tyrosine kinase or protein kinase A (PKA) up-regulated, Na+
      channels via modulating Na+ channel internalization, and/or Na+ channel
      externalization from the trans-Golgi network. Neuroprotective, antiepiletic,
      antipsychotic, and local anesthetic drugs up-regulated Na+ channels via
      transcriptional/translational events.

PMID- 14977602
TI  - Expression of cytochrome P450 in tumor tissues and its association with cancer
      development.
AB  - CYPs (cytochrome P450s) catalyze the conversion of numerous numbers of
      xenobiotics including carcinogens and drugs. CYPs can be involved in metabolic
      pathways of activation of procarcinogens and/or inactivation of carcinogens
      during the tumorigenic processes. Recently, increasing number of cancer tissues
      as well as normal tissues have been found to express a variety of CYPs. The local
      expression of CYPs in tumors appears to be very important for the management of
      cancers since CYPs expressed in tumors may be involved in activation and/or
      inactivation of anticancer drugs. The expression of CYPs in tumors may also
      convert endogenous substrates to metabolites that facilitate cancer development.
      In this review, we summarize the association of CYP expression in cancer tissues
      with carcinogenesis and cancer treatment.

PMID- 14977603
TI  - Prostaglandin E2 as a mediator of fever: synthesis and catabolism.
AB  - Prostaglandin (PG) E2 is a principal downstream mediator of fever. It is
      synthesized in three steps catalyzed by phospholipase (PL) A2, cyclooxygenase
      (COX), and terminal PGE synthase (PGES), where each catalytic activity is
      represented by multiple enzymes and/or isoenzymes. Inactivation of PGE2 occurs
      primarily in the lungs and liver via carrier-mediated cellular uptake and
      enzymatic oxidation. The two principal carriers are PG transporter (PGT) and
      multispecific organic anion transporter (MOAT); the two principal PGE2
      inactivating enzymes are 15-hydroxy-PG dehydrogenase (15-PGDH) and carbonyl
      reductase (CR). Our data [Ivanov A. I. et al. Am J Physiol Regul Integr Comp
      Physiol 283, R1104-R1117 (2002); ibid. 284, R698-R706 (2003)] are used to analyze
      the relationship between transcriptional regulation of PLA2, COX, PGES, PGT,
      MOAT, 15-PHDH, and CR, on one hand, and the triphasic febrile response of rats to
      lipopolysaccharide (LPS), on the other. It is concluded that LPS fever is
      accompanied by up-regulation of four PGE2-synthesizing enzymes [secretory (s)
      PLA2-IIA, cytosolic (c) PLA2-alpha, COX-2, and microsomal (m) PGES-1] and down
      regulation of all PGE2 carriers and dehydrogenases studied (PGT, MOAT, 15PGDH,
      and CR). It is further concluded that different febrile phases employ different
      mechanisms to mount an increase in the PGE2 level. Phase 1 involves
      transcriptional up-regulation of the couple COX-2 -->mPGES-1 in the liver and
      lungs. Phase 2 entails robust up-regulation of the major inflammatory triad sPLA2
      IIA -->COX-2 -->mPGES-1 throughout the body. Phase 3 involves induction of cPLA2
      alpha in the hypothalamus and further up-regulation of sPLA2-IIA and mPGES
      throughout the body. Importantly, Phase 3 occurs despite a drastic decrease in
      the expression of COX-1 and -2 in both the brain and periphery, thus suggesting
      that transcriptional up-regulation of COX-2 is not an obligatory mechanism of
      PGE2-dependent inflammatory responses at later stages. Of importance is also that
      LPS fever is accompanied by transcriptional down-regulation of PGE2 transporters
      and dehydrogenases: 15-PGDH in the lungs at Phase 1; 15-PGDH and CR in the lungs
      at Phase 2; and PGT, MOAT, 15-PGDH, and CR in the liver and lungs at Phase 3. The
      transcriptional down-regulation of proteins involved in PGE2 inactivation is a
      largely unrecognized mechanism of systemic inflammation. By increasing the blood
      brain gradient of PGE2, this mechanism likely facilitates penetration of PGE2
      into the brain. The high magnitude of up-regulation of mPGES and sPLA2-IIA (1,260
      and 130 fold, respectively) and that of down-regulation of 15-PGES (30 fold)
      during LPS fever makes these enzymes attractive targets for anti-inflammatory
      therapy.

PMID- 14977604
TI  - The effect of movement amplitude and target diameter on reaction time.
AB  - Henry's (Henry & Rogers, 1960) memory drum model of neuromotor reaction, which
      predicts an increased response latency for more complicated movements, was tested
      by examining the effects of variations in movement amplitude and target diameter
      on choice RT. RT tended to increase with decreasing target diameter, and varied
      as a U-shaped function with amplitude. Such findings were in only partial support
      of the memory of drum notion. The data were discussed in relation to information
      processing, muscle activation, and subjects' expectations for executing responses
      along the range of movement amplitude.

PMID- 14977605
TI  - An electrophysiological model of human visual reaction time.
AB  - Human visual reaction times were fractionated into component latencies measuring
      visual reception time, opto-motor integration time, central motor outflow time,
      and peripheral motor time on the basis of evoked cortical activity recorded from
      the intact scalp and the occurrence of the response electromyogram. Normative
      data are presented for a right-foot dorsiflexion task studied on 18 male
      subjects, together with an analysis of inter- and intra-subject variability in
      response timing. Faster reactors were found to display briefer opto-motor
      integration times and motor times, while an individual's faster responses were
      characterized by shorter motor outflow times and motor time. These results are
      interpreted in terms of varying physiological mechanisms.

PMID- 14977606
TI  - The effect of visual guidance on the acquisition of a simple motor task.
AB  - Subjects were required to learn to depress a bar using concurrent visual
      feedback, which was removed for test. The overshooting found in test is
      attributed to visual dominance of the feedback traces; the way in which it occurs
      is not clear, since the reduction of the ratio of movement to display gain from
      1:15 to 1:7.5 did not reduce overshooting. Performance improved after extended
      practice, but the direction of error remained positive. The results are discussed
      in terms of motor programming and feedback control of movement and are
      interpreted as evidence against Adams' (1971) two-trace theory.

PMID- 14977607
TI  - Startle response and muscular fatigue effects upon fractionated hand grip
      reaction time.
AB  - The fractionation of a simple right-hand grip total reaction time (RT) into
      central and peripheral temporal components (premotor and motor time,
      respectively) helped to define the site of RT change following an auditory
      induced startle response and two fatiguing hand-grip exercise regiments for eight
      males and eight females. Following the startle response, mean values for RT
      significantly lengthened, due primarily to an increase in premotor time. In
      contrast, lengthened RT following both fatigue regimens (42% and 55% strength
      decrements) were due to substantial increases in the motor time component. These
      results suggest that although performance of tasks which demand a high degree of
      precision, accuracy, and fine motor control may be disrupted by the introduction
      of such stressors as an induced startle and local muscular fatigue, the
      neuromuscular mechanisms mediating performance disruption are dissimilar.

PMID- 14977608
TI  - Transfer of reaction inhibition.
AB  - A serious challenge to Hull's (1943) theory of reminiscence and intertrial
      interval effects is posed by the current contention that reactive inhibition (In)
      must be task-specific since it does not seem to transfer from one task to
      another. This notion was examined within the framework of a practice-rest
      paradigm in which three control groups were given 20 1-min trials on a principal
      task with intertrial intervals of 0, 5, and 70 sec, respectively, while two
      experimental groups practiced alternately on the principal task and a secondary
      task known to produce evidence for I(R). The two secondary tasks varied in their
      similarities to the principal task. Additional control groups were used to assess
      the magnitude of habit transfer effects. The total sample consisted of 70 males
      and 70 females whose modal age was 18 yr. With habit transfer effects controlled,
      results showed clearly that work effects transferred from the alternate tasks to
      the main task without regard for differences in similarity. Thus, the task
      specificity hypothesis was not supported.

PMID- 14977609
TI  - Response programming, as assessed by reaction time, does not establish commands
      for particular muscles.
AB  - In previous studies, response programming has been inferred from a relation
      between reaction time and the nature of the response which follows. However, it
      has not been clear whether this programming process generates commands for
      specific muscles or abstract timing networks which can be applied to any
      appropriate muscle group. Experiment 1 employed the Sternberg (1969) additive
      factor method to show that muscle selection need not be completed before such
      programming begins, a conclusion which is inconsistent with the view that this
      process establishes commands to previously selected muscles. Experiments 2 and 3
      provide converging evidence against the muscle-specific view of programming by
      showing that advance programming of response timing can occur when the response
      muscle is not specified. A theoretical framework encompassing these and previous
      results is proposed.

PMID- 14977610
TI  - Eye movements during coincidence-anticipation performance.
AB  - The present study related visual processing, as indicated by eye movements, to
      performance accuracy on coincidence-anticipation tasks. Three age groups were
      tested on a coincidence-anticipation task and their eye movements recorded. Three
      levels of response were administered under three levels of stimulus speed. A
      MANOVA indicated that both eye tracking and coincidence-anticipation varied among
      the age groups and with stimulus speed, although in different directions. Eye
      tracking error decreased with increasing age but only the coincidence
      anticipation response accuracy of the youngest group appeared to be less accurate
      than that of the adults. Eye tracking error also decreased with decreasing
      stimulus speed but coincidence-anticipation performance was least accurate at the
      slow speed. Coincidence-anticipation error was the major contributor to
      performance differences with changes in the type of response.

PMID- 14977611
TI  - Serial-position effects in motor short-term memory.
AB  - This study examined the effect of the length of a series of movements on the
      recall of those movements. Subjects (n = 45) were randomly assigned to one of
      three experimental groups with each group recalling either three, six, or nine
      movements on a linear-slide apparatus. The subjects, while blindfolded, were
      presented with each movement by actively moving to a stop. Recall occurred 5 sec
      after the last movement to a stop on a trial. All subjects were given nine
      trials, each containing a different series of to-be-recalled movements. Results
      indicated that absolute error of recall of the three movements increased in a
      linear fashion. However, for six and nine movements, a bowing effect of the
      recall curve was noted following the fifth position. A primacy effect was more
      evident than was a recency effect. Accuracy of recall was a function of list
      length up to six movements, after which accuracy was not further impaired.

PMID- 14977612
TI  - Learner-centered versus automatic adaptive motor skill training.
AB  - Three types of training (fixed-difficulty, automatic-adaptive, and learner
      centered) were used to teach 18 male and 18 female students a two-dimensional
      pursuit-tracking task. A 7-min tracking session, in which task difficulty shifted
      each minute, was used to measure transfer. Although training type did not result
      in differences in training time, students trained under learner-centered
      procedures had less tracking error during transfer. Females required on the
      average twice as much training as mates. During transfer no sex differences were
      noted. The differences in training time for males and females may reflect
      previous experience with similar motor-control tasks.

PMID- 14977613
TI  - An analysis of motor coordination components for various localization tasks.
AB  - Localization abilities of subjects in three perceptual-motor tasks were
      considered before and after an exposure to a visual distortion. During this
      distortion the subject observed his hand ballistically point to an invisible but
      audible target while either receiving or not receiving knowledge of results (KR)
      concerning pointing accuracy. Also, subjects either received a 1- or a 4-sec rest
      period between each of 30 exposure ballistic pointing actions. The pre- and
      postexposure tasks involved the ability of a subject to accurately point to an
      occluded and stationary auditory target, to point to the straight-ahead position
      in space, and to indicate when a moving, auditory target was perceived as being
      in the straight-ahead position. For these tasks, the pre- vs. postexposure
      localization difference scores are referred to as the negative aftereffect, the
      proprioceptive shift, and the auditory shift, respectively. Wilkinson's (1971)
      two-component additive model (negative aftereffect = proprioceptive shift plus
      auditory shift) held when KR was given regardless of amount of rest between
      exposure pointing responses. With a 4-sec rest and no KR, the relationship
      between coordination components was nonadditive (negative aftereffect greater
      than proprioceptive shift plus auditory shift).

PMID- 14977614
TI  - An "exhaustive" search for tasks that fall between the choice and simple
      reactions.
AB  - An experimental search was made for reaction time (RT) tasks that require the
      processing operation of stimulus discrimination or response selection, but not
      both. The existence of such a task would allow the subtractive determination of
      the mean duration of the separate operations. Each of the three reactions that
      historically have been represented as possessing only one of the two operations
      was subjected to empirical testing. None of them met the most basic requirements.
      Donders' (1868/1969) contingent (c) reaction and Taylor's (1966) selection
      (b')reaction were not reliably faster than a compatible choice (b) reaction.
      Wundt's (1880) discrimination (d) reaction was not sensitive to difficulty of
      discrimination. The possibility is suggested that stimulus discrimination and
      response selection in the choice reaction are inseparable operations. The present
      negative results emphasize the importance of establishing validity of any use of
      the subtraction method through appropriate experimental methods. Some parallels
      of the compatibility issue are found in experiments in which RT is used as a
      measure of the duration of programming operations.

PMID- 14977615
TI  - Changes in pinch force with bidirectional load forces.
AB  - The forces used to grasp an object were measured while positive (push) and
      negative (pull) load forces were applied to the hand under varying frictional
      conditions. Subjects held between the tips of their thumb and index finger a
      manipulandum composed of two symmetrically mounted disks. The manipulandum was
      connected to the stage of an electromagnetic linear motor that generated load
      forces under computer control. In the first experiment, subjects held the
      position of the manipulandum constant while the motor generated forces in first
      the positive and then the negative direction. The motor force at which the
      manipulandum slipped from the fingers was measured in the second experiment. In
      both experiments, friction was varied by changing the surface (sandpaper, suede,
      or plastic) of the manipulandum disks. The pinch forces produced by subjects were
      linearly related to changes in motor force in both the positive and negative
      directions, with the slope of this relation varying as a function of the surface
      properties of the manipulandum. The modulation of pinch force with motor force
      was influenced, however, by the direction of the load force; higher forces were
      produced in response to negative load forces. Slip forces varied as a function of
      pinch force and surface texture; higher forces were associated with materials
      with lower coefficients of friction. These findings suggest that the friction
      between the skin and an object being grasped changes as a function of the
      direction of force that the object applies to the skin, possibly due to the
      anisotropic nature of glabrous skin, and that this mechanical property
      contributes to variations in pinch force.

PMID- 14977616
TI  - Timing and motor control in clumsy children.
AB  - The study examined timing control in clumsy children and employed the Wing
      Kristofferson (1973) model of repetitive movements in an attempt to identify the
      locus of timing control difficulties in clumsy children. Two groups of children
      classified as normal and clumsy (ages 6-7 and 9-10) performed tapping and
      perception of duration and loudness tasks. Results indicated that clumsy children
      were significantly more variable than normal children in maintaining a set rate
      of tapping and in accurately judging time intervals. Evidence indicated that the
      source of timing control problems in clumsy children may be in a central
      timekeeping mechanism, possibly the cerebellum.

PMID- 14977617
TI  - The effects of objectives and constraints on motor control strategy in reciprocal
      aiming movements.
AB  - The goal of this study was to examine how the kinematics of reciprocal aiming
      movements were affected by both the objective of the movement and the constraints
      operating on that movement. In Experiment 1, the objective of the movement was
      indirectly manipulated by capitalizing on the fact that subjects determine their
      own accuracy and speed limits, despite uniform task instructions to move as
      quickly and accurately as possible. A Fitts' type reciprocal aiming paradigm was
      employed, in which 69 subjects were asked to move a stylus repetitively between
      two spatially separated targets. Four target widths were orthogonally combined
      with four movement amplitudes, resulting in 16 conditions. Movements were made on
      an X-Y digitizing tablet. Based on the mean variable error produced on both
      targets, subjects were differentiated post hoc into three movement objective
      groups: speed, accuracy, and speed-plus-accuracy. Kinematic analyses revealed
      that the programming and execution of movements were systematically influenced by
      both the movement objective and the movement constraints. That is, movement time,
      peak velocity, dwell time, acceleration and deceleration time, normalized
      acceleration and normalized deceleration varied systematically as a function of
      both the speed-accuracy movement objective and the movement constraints of target
      size and movement distance. Moreover, the consequences of changing the
      constraints of the movement were affected by an interaction with the objective of
      the movement. In Experiment 2, the objective of the movement was directly
      manipulated by varying speed and/or accuracy instructions to subjects. The basic
      results of Experiment 1 were substantiated. Overall, the results were consistent
      with the view that motor control is dependent upon sensory consequences.

PMID- 14977618
TI  - Information feedback and the learning multiple-degree-of-freedom activities.
AB  - The influence of information feedback on the learning of a multiple-degree-of
      freedom activity, the overhand throw, was investigated. During learning, feedback
      was presented in the form of knowledge of results, knowledge of performance,
      knowledge of performance with attention-focusing cues, or knowledge of
      performance with error-correcting transitional information. Across 12 practice
      sessions, performance was assessed with respect to both throwing distance and
      throwing form. Subjects provided with knowledge of performance along with
      transitional information demonstrated significant gains in throwing distance,
      compared with subjects receiving knowledge of performance or knowledge of results
      alone. Movement form ratings followed the same trend. Providing learners with
      cues to focus their attention on the relevant aspects of knowledge of performance
      or directly providing transitional information was a better aid to the
      acquisition of throwing form than providing knowledge of results or knowledge of
      performance alone. These results support the hypothesis that knowledge of results
      may not be the most potent form of feedback in multiple-degree-of-freedom
      activities and that knowledge of performance, when combined with additional
      information, can lead to significant gains in skill acquisition.

PMID- 14977619
TI  - Performance on trials without knowledge results (KR) in reduced relative
      frequency presentations of KR.
AB  - Following Salmoni, Schmidt, & Walter's (1984) discussion of knowledge of results
      (KR) as a variable influencing learning, the effect of varying relative frequency
      of KR while holding absolute number of trials constant was examined. In two
      experiments, the same treatment groups were compared in acquisition, retention
      (after 2 min and 24 hr), and on their pattern of responses on the sequence of no
      KR trials following a KR trial. In Experiment 1, differences between groups in
      acquisition were consistent with the number of KR trials received, and there were
      no differences between groups in either of the retention conditions. Experiment 2
      replicated Experiment 1 with a more difficult task. There were no between-group
      differences in acquisition. In Retention 1, the 100% and 33% relative frequency
      groups outperformed the less frequent KR groups, whereas in Retention 2, this
      trend was reversed. The findings from Experiment 2 provide qualified support for
      the hypothesis that reduced relative frequency of KR in acquisition facilitates
      performance in retention. The pattern of responses on the sequence of no-KR
      trials following a KR trial were consistent with Adams' (1971) perceptual-trace
      decay hypothesis.

PMID- 14977620
TI  - Self-sitting and reaching in 5- to 8-month-old infants: the impact of posture and
      its development on early eye-hand coordination.
AB  - The relation between progress in the control of posture (i.e., the achievement of
      self-sitting posture) and the developmental transition from two-handed to one
      handed engagement in infant reaching was investigated. Two groups of 5- to 8
      month-old infants, who were either able or yet unable to sit on their own, were
      videotaped while they reached for objects in four different posture conditions
      that provided varying amounts of body support. Videotapes of infant reaches were
      microanalyzed to determine the relative engagement of both hands during reaches.
      Results demonstrate the interaction between postural development and the
      morphology of infant reaching. Nonsitting infants displayed symmetrical and
      synergistic engagement of both arms and hands while reaching in all but the
      seated posture condition. Sitting infants, by contrast, showed asymmetrical and
      lateralized (one-handed) reaches in all posture conditions. Results also show
      that, aside from posture, the perceived spatial arrangement of the object display
      is a determinant of infant reaching. Combined, these results are discussed as
      evidence for the interaction between postural and perceptual development in the
      control of early eye-hand coordination.

PMID- 14977621
TI  - A note on schema and exemplar approaches to motor skill representation in memory.
AB  - Given the need for a memory representation of well-learned motor skills, a common
      assumption in motor behavior is that this knowledge is stored in a central,
      abstracted form. Active production of motor skills has not been used in
      experimental designs that have provided empirical support for this view of
      representation, however. Much of the faith in centralized, abstracted forms of
      memory representation for motor skills is due to the popularity of Schmidt's
      schema theory, which has adapted the prototype abstraction model from category
      learning research to the representation of motor skills. Since schema theory was
      proposed, however, an alternative view that seriously questions the preeminence
      of the prototype abstraction model for the central representation of knowledge
      has arisen in the category learning literature. This particular view, termed the
      specific exemplar model, has led a number of researchers in cognition to develop
      mixed models that involve both prototypic abstraction and specific exemplar
      elements. This note, then, identifies what can be perceived as a gap in the
      empirical knowledge base in motor behavior and discusses the possibility of using
      the debate about representation for category learning as a stimulus for
      initiating a similar investigation into the representation of motor skills. A
      hypothetical specific exemplar model for the memory representation of motor
      skills is outlined, and possible empirical comparisons between this model and the
      schema abstraction model are suggested.

PMID- 14977622
TI  - Effects of inhaled furosemide on exertional dyspnea in chronic obstructive
      pulmonary disease.
AB  - The aim of this study is to investigate the effects of inhaled furosemide on the
      sensation of dyspnea produced during exercise in patients with stable chronic
      obstructive pulmonary disease (COPD). In a double-blind, randomized, crossover
      study we compared the effect of inhaled furosemide on dyspneic sensation during
      exercise testing with that of placebo. Spirometry and incremental and constant
      load exercise testing were performed after inhalation of placebo or furosemide on
      2 separate days in 19 patients with moderate or severe COPD. Subjects were asked
      to rate their sensation of respiratory discomfort using a 100-mm visual analog
      scale. There was significant improvement in mean FEV1 and FVC after inhalation of
      furosemide (p = 0.038 and 0.005, respectively) but not after placebo. At
      standardized exercise time during constant-load exercise testing but not during
      incremental exercise, the mean dyspneic visual analog scale score was lower after
      inhalation of furosemide compared with placebo (33.7 +/- 25.2 vs. 42.4 +/- 24.0
      mm, respectively, p = 0.014). We conclude that inhalation of furosemide
      alleviates the sensation of dyspnea induced by constant-load exercise testing in
      patients with COPD and that there is significant bronchodilation after inhalation
      of furosemide compared with placebo in these patients.

PMID- 14977623
TI  - Nitric oxide diffusing capacity and alveolar microvascular recruitment in
      sarcoidosis.
AB  - We measured diffusing capacities for carbon monoxide (DLCO) and nitric oxide,
      lung volume, and cardiac output by a rebreathing technique at two alveolar O2
      tensions (PAO2) at rest and exercise. Membrane diffusing capacity for CO (DMCO)
      and VC were estimated from DLCO by the Roughton-Forster (RF) method and also from
      simultaneous lung diffusing capacity for NO and DLCO measured at one O2 tension
      (modified RF method). Estimates by these methods agreed closely in normal
      subjects (Tamhane et al., Chest 2001;120:1850-1856). Using these methods, we
      studied patients with stages II-III pulmonary sarcoidosis to determine (1)
      whether the modified RF method accurately estimates DMCO and VC in parenchymal
      disease and (2) whether sarcoidosis alters recruitment of diffusing capacity with
      respect to cardiac output. In patients, DMCO and VC estimated by the two methods
      agreed closely. DMCO was disproportionately reduced relative to VC at any given
      cardiac output, and the slope of the relationship between DLCO and cardiac output
      was moderately, though significantly, below normal. We conclude that in
      sarcoidosis (1) the modified RF method provides comparable estimates of DMCO and
      VC as the standard RF method and (2) the limitation to diffusive gas transport
      resides primarily in the membrane barrier, although recruitment of microvascular
      reserves is also modestly impaired.

PMID- 14977624
TI  - Reducing atelectasis attenuates bacterial growth and translocation in
      experimental pneumonia.
AB  - Besides being one of the mechanisms responsible for ventilator-induced lung
      injury, atelectasis also seems to aggravate the course of experimental pneumonia.
      In this study, we examined the effect of reducing the degree of atelectasis by
      natural modified surfactant and/or open lung ventilation on bacterial growth and
      translocation in a piglet model of Group B streptococcal pneumonia. After
      creating surfactant deficiency by whole lung lavage, intratracheal instillation
      of bacteria induced severe pneumonia with bacterial translocation into the blood
      stream, resulting in a mortality rate of almost 80%. Treatment with 300 mg/kg of
      exogenous surfactant before instillation of streptococci attenuated both
      bacterial growth and translocation and prevented clinical deterioration. This
      goal was also achieved by reversing atelectasis in lavaged animals via open lung
      ventilation. Combining both exogenous surfactant and open lung ventilation
      prevented bacterial translocation completely, comparable to Group B streptococci
      instillation into healthy animals. We conclude that exogenous surfactant and open
      lung ventilation attenuate bacterial growth and translocation in experimental
      pneumonia and that this attenuation is at least in part mediated by a reduction
      in atelectasis. These findings suggest that minimizing alveolar collapse by
      exogenous surfactant and open lung ventilation may reduce the risk of pneumonia
      and subsequent sepsis in ventilated patients.

PMID- 14977625
TI  - Attenuation of acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary
      hypertension in mice by inhibition of Rho-kinase.
AB  - RhoA GTPase mediates a variety of cellular responses, including activation of the
      contractile apparatus, growth, and gene expression. Acute hypoxia activates RhoA
      and, in turn, its downstream effector, Rho-kinase, and previous studies in rats
      have suggested a role for Rho/Rho-kinase signaling in both acute and chronically
      hypoxic pulmonary vasoconstriction. We therefore hypothesized that activation of
      Rho/Rho-kinase in the pulmonary circulation of mice contributes to acute hypoxic
      pulmonary vasoconstriction and chronic hypoxia-induced pulmonary hypertension and
      vascular remodeling. In isolated, salt solution-perfused mouse lungs, acute
      administration of the Rho-kinase inhibitor Y-27632 (1 x 10(-5) M) attenuated
      hypoxic vasoconstriction as well as that due to angiotensin II and KCl. Chronic
      treatment with Y-27632 (30 mg x kg(-1) x day(-1)) via subcutaneous osmotic pump
      decreased right ventricular systolic pressure, right ventricular hypertrophy, and
      neomuscularization of the distal pulmonary vasculature in mice exposed to
      hypobaric hypoxia for 14 days. Analysis of a small number of proximal pulmonary
      arteries suggested that Y-27632 treatment reduced the level of phospho-CPI-17, a
      Rho-kinase target, in hypoxic lungs. We also found that endothelial nitric oxide
      synthase protein in hypoxic lungs was augmented by Y-27632, suggesting that
      enhanced nitric oxide production might have played a role in the Y-27632-induced
      attenuation of chronically hypoxic pulmonary hypertension. In conclusion, Rho/Rho
      kinase activation is important in the effects of both acute and chronic hypoxia
      on the pulmonary circulation of mice, possibly by contributing to both
      vasoconstriction and vascular remodeling.

PMID- 14977626
TI  - Influence of maturation on constrictive response to stimulation of C-fiber
      afferents in isolated guinea pig airways.
AB  - We investigated whether the airway constrictive response to stimulation of
      bronchopulmonary C-fiber afferents is altered during the maturation process.
      Isometric tension was measured in airway rings isolated from three
      tracheobronchial locations (intrathoracic trachea and main and hilar bronchi) and
      compared in mature [M, 407 +/- 10 (SE) g body wt, n = 36] and immature (IM, 161
      +/- 5 g body wt, n = 35) guinea pigs. Our results showed no difference in the ACh
      (10(-5) M)- or KCl (40 mM)-induced contraction between M and IM groups,
      regardless of the airway location. In sharp contrast, the concentration-response
      curves of 10(-8)-10(-6) M capsaicin were distinctly lower in IM hilar bronchi;
      for example, response to the same concentration of capsaicin (10(-6) M) was 89.2
      +/- 15.3% of the response to 10(-5) M ACh in IM and 284.7 +/- 43.2% in M animals.
      Similar, but smaller, differences in the bronchoconstrictive response to
      capsaicin between IM and M groups were also observed in the trachea and main
      bronchus. Electrical field stimulation induced airway constriction in all three
      locations in M and IM groups. However, after administration of 10(-6) M atropine
      and 10(-6) M propranolol, electrical field stimulation-induced contraction was
      significantly smaller in the hilar bronchus of IM than M animals, and this
      difference was not prevented by pretreatment with 5 x 10(-5) M indomethacin.
      Although radioimmunoassay showed no difference in the tissue content of substance
      P between M and IM airways, the constrictive responses to exogenous substance P
      and neurokinin A were markedly greater in M airways at all three locations. In
      conclusion, the constriction of isolated airways evoked by C-fiber stimulation
      was significantly weaker in the IM guinea pigs, probably because of a less potent
      effect of tachykinins on the airway smooth muscle.

PMID- 14977627
TI  - Arginase inhibition increases nitric oxide production in bovine pulmonary
      arterial endothelial cells.
AB  - Nitric oxide (NO) is produced by NO synthase (NOS) from L-arginine (L-Arg).
      Alternatively, L-Arg can be metabolized by arginase to produce L-ornithine and
      urea. Arginase (AR) exists in two isoforms, ARI and ARII. We hypothesized that
      inhibiting AR with L-valine (L-Val) would increase NO production in bovine
      pulmonary arterial endothelial cells (bPAEC). bPAEC were grown to confluence in
      either regular medium (EGM; control) or EGM with lipopolysaccharide and tumor
      necrosis factor-alpha (L/T) added. Treatment of bPAEC with L/T resulted in
      greater ARI protein expression and ARII mRNA expression than in control bPAEC.
      Addition of L-Val to the medium led to a concentration-dependent decrease in urea
      production and a concentration-dependent increase in NO production in both
      control and L/T-treated bPAEC. In a second set of experiments, control and L/T
      bPAEC were grown in EGM, EGM with 30 mM L-Val, EGM with 10 mM L-Arg, or EGM with
      both 10 mM L-Arg and 30 mM L-Val. In both control and L/T bPAEC, treatment with L
      Val decreased urea production and increased NO production. Treatment with L-Arg
      increased both urea and NO production. The addition of the combination L-Arg and
      L-Val decreased urea production compared with the addition of L-Arg alone and
      increased NO production compared with L-Val alone. These data suggest that
      competition for intracellular L-Arg by AR may be involved in the regulation of
      NOS activity in control bPAEC and in response to L/T treatment.

PMID- 14977628
TI  - Malnutrition impairs alveolar fluid clearance in rat lungs.
AB  - Inadequate nutrition complicates the clinical course of critically ill patients,
      and many of these patients develop pulmonary edema. However, little is known
      about the effect of malnutrition on the mechanisms that resolve alveolar edema.
      Therefore, we studied the mechanisms responsible for the decrease in alveolar
      fluid clearance in rats exposed to malnutrition. Rats were allowed access to
      water, but not to food, for 120 h. Then, the left and right lungs were isolated
      for the measurement of lung water volume and alveolar fluid clearance,
      respectively. The rate of alveolar fluid clearance was measured by the
      progressive increase in the concentration of Evans blue dye that was instilled
      into the distal air spaces with an isosmolar 5% albumin solution over 1 h.
      Malnutrition decreased alveolar fluid clearance by 38% compared with controls.
      Amiloride (10(-3) M) abolished alveolar fluid clearance in malnourished rats.
      Either refeeding for 120 h following nutritional deprivation for 120 h or an oral
      supply of sodium glutamate during nutritional deprivation for 120 h restored
      alveolar fluid clearance to 91 and 86% of normal, respectively. Dibutyryl-cGMP, a
      cyclic nucleotide-gated cation channel agonist, increased alveolar fluid
      clearance in malnourished rats supplied with sodium glutamate. Terbutaline, a
      beta(2)-adrenergic agonist, increased alveolar fluid clearance in rats under all
      conditions (control, malnutrition, refeeding, and glutamate-treated). These
      results indicate that malnutrition impairs primarily amiloride-insensitive and
      dibutyryl-cGMP-sensitive alveolar fluid clearance, but this effect is partially
      reversible by refeeding, treatment with sodium glutamate, or beta-adrenergic
      agonist therapy.

PMID- 14977629
TI  - Carboxypeptidase-mediated enhancement of nitric oxide production in rat lungs and
      microvascular endothelial cells.
AB  - Membrane-bound regulatory carboxypeptidases cleave only COOH-terminal basic
      residues from peptides and proteins. To investigate whether carboxypeptidase
      generated arginine can increase nitric oxide (NO) synthesis we perfused rat lungs
      from animals challenged with LPS or used rat lung microvascular endothelial cells
      (RLMVEC) stimulated with LPS and IFN-gamma, conditions that induced inducible NO
      synthase (iNOS) expression. Addition of carboxypeptidase substrate furylacryloyl
      Ala-Arg (Fa-A-R) or Arg to the lung perfusate increased NO production two- to
      threefold. The carboxypeptidase inhibitor 2-mercaptomethyl-3
      guanidinoethylthiopropanoic acid (MGTA) blocked the effect of Fa-A-R but not free
      Arg. Lysine, an Arg transport inhibitor, blocked the increase in NO stimulated by
      Fa-A-R. HPLC analysis showed that Fa-A-R hydrolysis was blocked by MGTA but not
      lysine. In cytokine-treated RLMVEC, Fa-A-R also stimulated NO production
      inhibited by MGTA or lysine. Membrane fractions from rat lungs or RLMVEC
      contained carboxypeptidase M-like activity at neutral pH that increased twofold
      in RLMVEC treated with LPS + IFN-gamma. The kinetics of NO production in RLMVEC
      was measured with a porphyrinic microsensor. Addition of 1 mM Arg or Fa-A-R to
      cells preincubated in Arg-free medium resulted in a slowly rising, prolonged (>20
      min) NO output. NO production stimulated by Fa-A-R was blocked by MGTA or iNOS
      inhibitor 1400W. HPLC analysis of Fa-A-R hydrolysis revealed only 3.7 microM Arg
      was released over 20 min. Thus NO production in RLMVEC is stimulated more
      efficiently by Arg released from carboxypeptidase substrates than free Arg. These
      studies reveal a novel mechanism by which the Arg supply for NO production in
      inflammatory conditions may be maintained.

PMID- 14977630
TI  - Altered bleomycin-induced lung fibrosis in osteopontin-deficient mice.
AB  - Osteopontin is a multifunctional matricellular protein abundantly expressed
      during inflammation and repair. Osteopontin deficiency is associated with
      abnormal wound repair characterized by aberrant collagen fibrillogenesis in the
      heart and skin. Recent gene microarray studies found that osteopontin is
      abundantly expressed in both human and mouse lung fibrosis. Macrophages and T
      cells are known to be major sources of osteopontin. During lung fibrosis,
      however, osteopontin expression continues to increase when inflammation has
      receded, suggesting alternative sources of ostepontin during this response. In
      this study, we demonstrate immunoreactivity for osteopontin in lung epithelial
      and inflammatory cells in human usual interstitial pneumonitis and murine
      bleomycin-induced lung fibrosis. After treatment with bleomycin, osteopontin-null
      mice develop lung fibrosis characterized by dilated distal air spaces and reduced
      type I collagen expression compared with wild-type controls. There is also a
      significant decrease in levels of active transforming growth factor-beta(1) and
      matrix metalloproteinase-2 in osteopontin null mice. Type III collagen expression
      and total collagenase activity are similar in both groups. These results
      demonstrate that osteopontin expression is associated with important fibrogenic
      signals in the lung and that the epithelium may be an important source of
      osteopontin during lung fibrosis.

PMID- 14977631
TI  - Genomic structure and promoter characterization of the human Sprouty4 gene, a
      novel regulator of lung morphogenesis.
AB  - The expression of Sprouty4 (Spry4), an intracellular FGF receptor antagonist,
      shows a temporally and spatially restricted pattern in embryonic lung and is
      induced by ERK signaling. To clarify the molecular mechanisms regulating Spry4
      transcription, the genomic structure of the human Sprouty4 (hSpry4) gene was
      first determined by using the GenomeWalker kit. The hSpry4 gene spans > 14 kb and
      is organized in three exons and two introns. Multiple transcription start sites
      were subsequently mapped by 5'-rapid amplification of cDNA ends. Analysis of up
      to 4 kb of sequence in the 5'-flanking region of the gene showed the presence of
      multiple potential transcription factor binding sites but no TATA or CAAT boxes.
      Transient transfection using luciferase reporter gene constructs with progressive
      deletions of the hSpry4 5'-flanking region revealed that the core promoter
      activity is located within the proximal 0.4-kb region, whereas the minimal ERK
      inducible promoter activity is between -69 and -31. Homology analysis further
      showed that the core promoter region of the hSpry4 gene exhibits significant
      similarity to the 5'-flanking region of the mouse gene.

PMID- 14977632
TI  - Essential role for cathepsin D in bleomycin-induced apoptosis of alveolar
      epithelial cells.
AB  - Our earlier studies showed that bleomycin-induced apoptosis of type II alveolar
      epithelial cells (AECs) requires the autocrine synthesis and proteolytic
      processing of angiotensinogen into ANG II and that inhibitors of ANG-converting
      enzyme (ACEis) block bleomycin-induced apoptosis (Li X, Zhang H, Soledad-Conrad
      V, Zhuang J, and Uhal BD. Am J Physiol Lung Cell Mol Physiol 284: L501-L507,
      2003). Given the documented role of cathepsin D (CatD) in apoptosis of other cell
      types, we hypothesized that CatD might be the AEC enzyme responsible for the
      conversion of angiotensinogen into ANG I, the substrate for ACE. Primary cultures
      of rat type II AECs challenged with bleomycin in vitro showed upregulation and
      secretion of CatD enzymatic activity and immunoreactive protein but no increases
      in CatD mRNA. The aspartyl protease inhibitor pepstatin A, which completely
      blocked CatD enzymatic activity, inhibited bleomycin-induced nuclear
      fragmentation by 76% and reduced bleomycin-induced caspase-3 activation by 47%.
      Antisense oligonucleotides against CatD mRNA reduced CatD-immunoreactive protein
      and inhibited bleomycin-induced nuclear fragmentation by 48%. A purified fragment
      of angiotensinogen (F1-14) containing the CatD and ACE cleavage sites, when
      applied to unchallenged AEC in vitro, yielded mature ANG II peptide and induced
      apoptosis. The apoptosis induced by F1-14 was inhibited 96% by pepstatin A and
      77% by neutralizing antibodies specific for CatD (both P < 0.001). These data
      indicate a critical role for CatD in bleomycin-induced apoptosis of cultured AEC
      and suggest that the role(s) of CatD in AEC apoptosis include the conversion of
      newly synthesized angiotensinogen to ANG II.

PMID- 14977633
TI  - Secretagogue-induced translocation of CRHSP-28 within an early apical endosomal
      compartment in acinar cells.
AB  - Ca(2+)-regulated heat-stable protein (CRHSP-28) is a member of the TPD52 protein
      family that has been shown to regulate Ca(2+)-dependent secretory activity in
      pancreatic acinar cells. Immunofluorescence microscopy of isolated lobules
      demonstrated that CRHSP-28 is localized to a supranuclear apical compartment in
      acini and accumulates immediately below the apical membrane within 2 min of CCK
      octapeptide (CCK-8) stimulation. Dual-immunofluorescence microscopy demonstrated
      an endosomal localization of CRHSP-28 that strongly overlapped with early
      endosomal antigen-1 (EEA-1) on vesicular structures throughout the apical
      cytoplasm but showed only minimal overlap with the transferrin receptor, which is
      present in basolaterally derived endosomes. Significant overlapping of CRHSP-28
      with the trans-Golgi network marker-38 was also noted in supranuclear regions of
      acini. Interestingly, treatment of lobules with brefeldin A reversibly disrupted
      the vesicular localization of CRHSP-28 and EEA-1 within the apical cytoplasm. The
      CCK-8-induced accumulation of CRHSP-28 in subapical regions of acini was not
      altered by inhibition of apical endocytosis with the actin filament-disrupting
      agent latrunculin B. Immunoelectron microscopy confirmed that CRHSP-28 is
      associated with the limiting membrane of irregularly shaped vesicular structures
      of low electron density in the apical cytoplasm that are positive for EEA-1
      staining. Sparse, but significant, CRHSP-28 immunoreactivity was also observed
      along the limiting membrane of zymogen granules. Consistent with
      immunofluorescence data, CRHSP-28 was found to accumulate in clusters on
      endosomes and positioned between zymogen granules below the cell apex on CCK-8
      stimulation. These data indicate that CRHSP-28 is present within endocytic and
      exocytic compartments of acinar cells and is acutely regulated by secretagogue
      stimulation.

PMID- 14977634
TI  - Generation and characterization of immortalized rat pancreatic stellate cells.
AB  - Pancreatic stellate cells (PSCs) are involved in, among other things, the
      pathogenesis of pancreatic fibrosis. Here, we present the generation of
      immortalized PSCs 7 and 14 days after isolation by retroviral gene transfer of
      the SV40 large T antigen encoding region. Propagated cell lines [large T
      immortalized cells (LTC)-7, LTC-14] retained characteristics of primary cells in
      terms of morphology, responsiveness to mediators regulating cellular functions
      such as proliferation, and expression profile of a number of investigated genes.
      Whereas LTC-14 kept the morphological features of the differentiation status of
      the primary cells they were made of, LTC-7 appeared similar to an earlier stage.
      Thus the established cell lines represent a versatile tool to investigate various
      aspects of PSC biology.

PMID- 14977635
TI  - Changes in membrane cholesterol affect caveolin-1 localization and ICC-pacing in
      mouse jejunum.
AB  - Pacing of mouse is dependent on the spontaneous activity of interstitial cells of
      Cajal in the myenteric plexus (ICC-MP). These ICC, as well as intestinal smooth
      muscle, contain small membrane invaginations called caveolae. Caveolae are
      signaling centers formed by insertions of caveolin proteins in the inner aspect
      of the plasma membrane. Caveolins bind signaling proteins and thereby negatively
      modulate their signaling. We disrupted caveolae by treating intestinal segments
      with methyl beta-clodextrin (CD) to remove cholesterol or with water-soluble
      cholesterol (WSC) to load cholesterol. Both of these treatments reduced pacing
      frequencies, and these effects were reversed by the other agent. These treatments
      also inhibited paced contractions, but complete reversal was not observed. To
      evaluate the specificity of the effects of CD and WSC, additional studies were
      made of their effects on responses to carbamoyl choline and to stimulation of
      cholinergic nerves. Neither of these treatments affected these sets of responses
      compared with their respective time controls. Immunochemical and ultrastructural
      studies showed that caveolin 1 was present in smooth muscle membranes and ICC-MP.
      CD depleted both caveolin 1 and caveolae, whereas WSC increased the amount of
      caveolin 1 immunoreactivity and altered its distribution but failed to increase
      the number of caveolae. The effects of each agent were reversed in major part by
      the other. We conclude that signaling through caveolae may play a role in pacing
      by ICC but does not affect responses to acetylcholine from nerves or when added
      exogenously.

PMID- 14977636
TI  - Symptom hypersensitivity to acid infusion is associated with hypersensitivity of
      esophageal contractility.
AB  - Several investigators have observed that repeated acid infusions induce stronger
      symptoms (symptom hypersensitivity). The goal of our study was to determine
      whether symptom hypersensitivity is associated with esophageal contractile
      hypersensitivity. Subjects with chronic heartburn symptoms underwent simultaneous
      pressure and ultrasound imaging of esophagus. Normal saline and 0.1 N HCl were
      sequentially infused into the esophagus, and subjects scored heartburn symptoms
      on a 1-10 scale. Saline and HCl infusions were repeated in 10 subjects with a
      positive Bernstein test. Esophageal contraction amplitude and duration and
      muscularis propria thickness were measured using a computerized method during
      recording. Acid infusion induced heartburn. Esophageal contractions had higher
      amplitudes (pressure 114.2 +/- 7.0%) and longer duration (116.8 +/- 4.4%) during
      acid infusion compared with saline infusion. Average muscle thickness was greater
      during acid infusion than saline infusion (107.0 +/- 2.0%). Sustained esophageal
      contractions (SECs) were identified during acid infusion. A second acid infusion
      (acid-2) induced heartburn with shorter latency (93.0 +/- 15.0 vs. 317.0 +/- 43.0
      s) and stronger severity (8.5 +/- 0.5 vs. 5.3 +/- 0.8) than the first acid
      infusion (acid-1). Contraction amplitudes (140.2 +/- 13.0%), average muscle
      thickness (118.0 +/- 3.3%), and contraction duration (148.5 +/- 5.6 vs. 116.8 +/-
      4.4%) were higher during acid-2 than acid-1. Also, numbers of SECs were greater
      during acid-2 than acid-1 (31 in 8 subjects vs. 11 in 6 subjects). Our data show
      that acid infusion into esophagus induces esophageal hypersensitivity and that a
      close temporal correlation exists between symptom hypersensitivity and
      contractility hypersensitivity.

PMID- 14977637
TI  - Cdx1 or Cdx2 expression activates E-cadherin-mediated cell-cell adhesion and
      compaction in human COLO 205 cells.
AB  - A mature columnar intestinal epithelium develops late in embryogenesis and is
      maintained throughout the life of the organism. Although the mechanisms driving
      intestine-specific gene expression have been well studied, those promoting the
      acquisition of cell-cell junctions, columnar morphogenesis, and polarization have
      been less studied. The Cdx homeodomain transcription factors (Cdx1 and Cdx2)
      regulate intestine-specific gene expression and intestinal epithelial
      differentiation. We report here that Cdx expression induces E-cadherin activity
      and cell-cell adhesion in human COLO 205 cancer cells. Within days of Cdx1 or
      Cdx2 expression, a new homotypic cell-cell adhesion phenotype is induced. This is
      a specific response to Cdx, inasmuch as a Cdx1 mutant failed to elicit the
      effect. Additionally, Cdx-expressing COLO 205 cells demonstrate a reduced
      proliferative capacity and an increase in the mRNA expression of differentiation
      associated genes. Electron micrographs of these cells demonstrate induction of
      tight, adherens, and desmosomal junctions, as well as a columnar shape and apical
      microvilli. Investigations of the adhesion phenotype determined that it was
      Ca(2+) dependent and could be blocked by an E-cadherin-blocking antibody.
      However, E-cadherin protein levels and intracellular distribution were unchanged.
      Cdx expression restored the ability of the cell membranes to adhere and undergo
      compaction. We conclude that Cdx1 or Cdx2 expression is sufficient to induce an E
      cadherin-dependent adhesion of COLO 205 cells. This adhesion is associated with
      polarization and cell-cell membrane compaction, as well as induction of a
      differentiated gene-expression pattern. Ascertaining the mechanism for this novel
      Cdx effect may yield insight into the development of mature colonic epithelium.

PMID- 14977638
TI  - Inducible nitric oxide synthase upregulates cyclooxygenase-2 in mouse
      cholangiocytes promoting cell growth.
AB  - Both inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2)
      have been implicated in the biliary tract carcinogenesis. However, it is not
      known whether these inflammatory mediators are induced by interdependent or
      parallel pathways. Because iNOS activity has been associated with diverse gene
      expression, the aim of this study was to determine whether iNOS induces COX-2. To
      address this objective, immortalized, but nonmalignant, murine cholangiocytes,
      603B cells were employed for these studies. Both iNOS and COX-2 protein and mRNA
      were expressed in these cells. However, iNOS inhibition with either N-[3
      (aminomethyl) benzyl]acetamidine or stable transfection with an iNOS antisense
      construct inhibited COX-2 mRNA and protein expression, an effect that was
      reversed by NO donors. COX-2 mRNA expression in 603B cells was reduced by
      pharmacological inhibitors of the p38 MAPK and JNK1/2 pathways. In contrast,
      neither inhibitors of the soluble guanylyl cyclase inhibitor/protein kinase G nor
      p42/44 MAPK pathways attenuated COX-2 mRNA expression. Finally, 603B cells grew
      at a rate threefold greater than 603B-iNOS antisense cells. The low growth rate
      of 603B-iNOS antisense cells could be restored to near that of the parent cell
      line with exogenous PGE(2.) In conclusion, iNOS induces COX-2 expression in
      cholangiocytes, which promotes cell growth. COX-2 induction may contribute to
      iNOS-associated carcinogenesis.

PMID- 14977639
TI  - Polymorphisms in genes involved in folate metabolism and colorectal neoplasia: a
      HuGE review.
AB  - Epidemiologic and mechanistic evidence suggests that folate is involved in
      colorectal neoplasia. Some polymorphic genes involved in folate metabolism-
      methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase
      (MTR A2756G), methionine synthase reductase (MTRR A66G), cystathionine beta
      synthase (CBS exon 8, 68-base-pair insertion), and thymidylate synthase (TS
      enhancer region and 3' untranslated region)--have been investigated in colorectal
      neoplasia. For MTHFR C677T and A1298C, the variant allele is associated with
      reduced enzyme activity in vitro. For the other polymorphisms, functional data
      are limited and/or inconsistent. Genotype frequencies for all of the
      polymorphisms show marked ethnic and geographic variation. In most studies, MTHFR
      677TT (10 studies, >4,000 cases) and 1298CC (four studies, >1,500 cases) are
      associated with moderately reduced colorectal cancer risk. In four of five
      genotype-diet interaction studies, 677TT subjects who had higher folate levels
      (or a "high-methyl diet") had the lowest cancer risk. In two studies, 677TT
      homozygote subjects with the highest alcohol intake had the highest cancer risk.
      Findings from six studies of MTHFR C677T and adenomatous polyps are inconsistent.
      There have been only one or two studies of the other polymorphisms; replication
      is needed. Overall, the roles of folate-pathway genes, folate, and related
      dietary factors in colorectal neoplasia are complex. Research priorities are
      suggested.

PMID- 14977640
TI  - Alcohol intake, drinking patterns, and risk of prostate cancer in a large
      prospective cohort study.
AB  - Alcohol drinking has been extensively studied in relation to prostate cancer, yet
      findings on the direction of the association are equivocal. Previous studies have
      not examined drinking patterns. Thus, the authors prospectively evaluated the
      associations between these factors and risk of incident prostate cancer (n =
      2,479) in a cohort study of 47,843 US men (1986-1998). The men completed a
      questionnaire at baseline that included information on consumption of specific
      types of alcohol and frequency of use. The authors estimated hazard ratios using
      Cox proportional hazards regression for average alcohol intake and number of days
      per week on which alcohol was consumed stratified by average weekly intake (<105
      g/week vs. > or = 105 g/week). Compared with nondrinking, the hazard ratio for
      consumption increased slightly from an average of 5.0-14.9 g/day (hazard ratio
      (HR) = 1.05, 95% confidence interval (CI): 0.94, 1.18) to 30.0-49.9 g/day (HR =
      1.13, 95% CI: 0.96, 1.33), but it was not increased at > or = 50 g/day (HR =
      1.00, 95% CI: 0.77, 1.31) after adjustment for recent smoking and other factors.
      Compared with abstainers, risk was greatest among men who consumed an average of
      > or = 105 g/week but who drank on only 1-2 days per week (HR = 1.64, 95% CI:
      1.13, 2.38). These results suggest that moderate or greater alcohol consumption
      is not a strong contributor to prostate cancer risk, except possibly in men who
      consume large amounts infrequently.

PMID- 14977641
TI  - Diet and nutrient intakes and risk of non-Hodgkin's lymphoma in Connecticut
      women.
AB  - A population-based case-control study (601 cases and 717 controls) was conducted
      in 1995-2001 among Connecticut women to evaluate the relation between diet and
      nutrient intakes and the risk of non-Hodgkin's lymphoma (NHL). When the highest
      quartile of intake was compared with the lowest, the authors found an increased
      risk of NHL associated with animal protein (odds ratio = 1.7, 95% confidence
      interval: 1.2, 2.4) and saturated fat (odds ratio = 1.9, 95% confidence interval:
      1.1, 2.3) but a reduced risk for polyunsaturated fat (odds ratio = 0.6, 95%
      confidence interval: 0.4, 0.9) and no relation for vegetable protein and
      monounsaturated fat. An increased risk was also observed for higher intakes of
      retinol, eggs, and dairy products. On the other hand, a reduced risk was found
      for higher intakes of dietary fiber and for several fruit and vegetable items.
      Risk of NHL associated with diet and nutrient intakes appeared to vary based on
      NHL subtype. An association between dietary intake and NHL risk is biologically
      plausible because diets high in protein and fat may lead to altered
      immunocompetence, resulting in an increased risk of NHL. The antioxidant or
      inhibiting nitrosation reaction properties of vegetables and fruits may result in
      a reduced risk. Further investigation of the role of dietary intakes on the risk
      of NHL is warranted.

PMID- 14977642
TI  - The dietary glycemic index during pregnancy: influence on infant birth weight,
      fetal growth, and biomarkers of carbohydrate metabolism.
AB  - During pregnancy, lower levels of maternal glucose before and during a glucose
      load have been associated with reduced infant birth weight and an increased risk
      of small-for-gestational-age births. A lower incremental area under the glucose
      response curve defines a low glycemic diet. Thus, during pregnancy the maternal
      diet, as measured by the glycemic index, may influence fetal growth and infant
      birth weight. A total of 1,082 gravidas who enrolled in the Camden Study between
      August 1996 and October 2002 were followed prospectively during pregnancy. The
      dietary glycemic index was computed from three 24-hour recalls in the course of
      pregnancy. Samples for plasma glucose and for glycosylated hemoglobin were
      obtained at 24-28 weeks' gestation. The glycemic index was positively and
      significantly related to maternal glycosylated hemoglobin and plasma glucose.
      There were as well significant linear trends for dietary fat intake to decrease
      and for intakes of carbohydrate, sucrose, fiber, and folate to increase as the
      glycemic index declined. Gravidas with a low dietary glycemic index had reduced
      infant birth weight and approximately a twofold increased risk of a small-for
      gestational-age birth. Consistent with data on maternal plasma glucose, data in
      this study show that the type of carbohydrate in the diet of urban, low-income
      women influences fetal growth and infant birth weight.

PMID- 14977643
TI  - Prevalence of induced abortion in a reproductive lifetime.
AB  - The period total first abortion rate (TFAR) has been used to estimate the
      proportion of women who will experience an induced abortion in their reproductive
      lifetime. It is a hypothetical measure as age-specific rates currently existing
      will change with time. Instead, a cohort TFAR has been calculated for women born
      around 1955 using legal-abortion reports in South Australia to calculate first
      abortion rates for each year of age from 15 years to 44 years for 1971-2000,
      respectively, and summing these. Yearly fertility rates were also calculated for
      this cohort to further describe their reproductive experience. Yearly first
      abortion rates were also calculated for later cohorts born in 1960-1980. The 1955
      cohort TFAR was 288.1 per 1,000 women aged 15-44 years. Cumulative first abortion
      rates at specific ages were higher for subsequent cohorts (e.g., 309.6 per 1,000
      at age 40 years for the 1960 cohort). Thus, about 29% of South Australian women
      born around 1955 and exposed to legal abortion throughout their reproductive
      lifetime experienced an induced abortion. This proportion would be higher for
      later cohorts of women born in 1960-1980 (e.g., at least 31% for those born in
      1960).

PMID- 14977644
TI  - Childhood and adult socioeconomic conditions and 31-year mortality risk in women.
AB  - Links between low socioeconomic position and poor health are well established.
      Most previous research, however, has focused on middle-aged males and has relied
      on limited socioeconomic data, usually measured at one point over the life
      course. This paper examines all-cause, cardiovascular, and noncardiovascular
      mortality in women in relation to socioeconomic position at different stages of
      the life course. Information was collected in 1965, 1974, 1983, and 1994 and
      included recalled father's occupation and education as a measure of childhood
      socioeconomic position and the respondent's household income, education and
      occupation, and spouse's occupation from a sample of 3,087 women participating in
      the Alameda County Study. Cox regression models were used to estimate hazard
      ratios for risk of death. Lower childhood socioeconomic position was associated
      with an increased mortality due to cardiovascular disease (hazard ratio (HR) =
      1.29, 95% confidence interval (CI): 1.09, 1.54) but was unrelated to death due to
      other causes (HR = 0.97, 95% CI: 0.82, 1.15). Overall mortality was higher among
      women reporting the lowest level of education (HR = 1.17, 95% CI: 0.99, 1.39),
      but education was most strongly related to noncardiovascular disease-related
      deaths (HR = 1.41, 95% CI: 1.10, 1.81). Low household income was also associated
      with higher mortality, for both cardiovascular disease-related (HR = 1.47, 95%
      CI: 1.14, 1.91) and noncardiovascular disease-related (HR = 1.30, 95% CI: 1.03,
      1.63) deaths. Both early and later life indicators of socioeconomic position
      contribute to increased mortality risk among socioeconomically disadvantaged
      women, but these effects appear stronger for cardiovascular mortality.

PMID- 14977645
TI  - Prevalence of foot and ankle conditions in a multiethnic community sample of
      older adults.
AB  - The prevalence of foot and ankle disorders was determined in a community-based,
      multiethnic (non-Hispanic White, African American, and Puerto Rican) random
      sample of 784 community-dwelling adults aged 65 or more years in 2001-2002 in
      Springfield, Massachusetts. Overall, the five most common conditions were toenail
      disorders (74.9%), lesser toe deformities (60.0%), corns and calluses (58.2%),
      bunions (37.1%), and signs of fungal infection, cracks/fissures, or maceration
      between toes (36.3%); 30.9% had some tenderness to palpation of the foot or
      ankle, and 14.9% had ankle joint pain on most days in the past 4 weeks. Toenail
      conditions, fungal symptoms, and ulcers or lacerations were more common in men,
      while bunions and corns and calluses were more common in women (p < 0.001).
      Significant racial/ethnic differences, independent of education or gender, were
      found for the prevalence of most toe deformities and flat feet, as well as for
      corns and calluses, fungal signs, edema, ankle joint pain, tenderness to
      palpation, and sensory loss. Foot and ankle disorders are common in these older
      adults. Examination of their prevalence in different segments of the community
      may inform future studies to determine etiology and means of prevention.

PMID- 14977646
TI  - Birth order, sibship size, and housing density in relation to tooth loss and
      periodontal disease: a cohort study among Swedish twins.
AB  - For diseases with an infectious etiology, birth order may dictate the age of
      exposure to childhood infection, while sibship size may be a proxy for the
      probability of exposure. The authors examined whether birth order, sibship size,
      and childhood housing density affect risk of tooth loss and periodontal disease.
      The study included 28,690 adults aged > or = 42 years who were participating in a
      1998-2002 follow-up of persons listed in the Swedish Twin Registry. Logistic
      regression was used to calculate odds ratios and 95% confidence intervals, with
      adjustment for age, sex, education, and smoking and mutual adjustment for family
      composition (sibship size and/or birth order). Tooth loss and periodontal disease
      affected 8% and 19% of the twins, respectively. Each additional sibling increased
      the odds of tooth loss by 10% (95% confidence interval (CI): 1.06, 1.15) and the
      odds of periodontal disease by 5% (95% CI: 1.02, 1.08). Later birth order was
      associated with lower odds of periodontal disease. Each additional person per
      room in the childhood home increased the odds of tooth loss (odds ratio = 1.28,
      95% CI: 1.03, 1.60) but lowered the odds of periodontal disease (odds ratio =
      0.65, 95% CI: 0.48, 0.89). These findings are compatible with the hypotheses that
      adult oral diseases are associated with the probability of exposure in childhood
      and that earlier age at exposure lowers risk.

PMID- 14977647
TI  - Diversity of Mycobacterium tuberculosis isolates in an immigrant population:
      evidence against a founder effect.
AB  - Population-based studies have used DNA typing of Mycobacterium tuberculosis
      organisms to estimate the extent of ongoing tuberculosis transmission in various
      communities and to characterize associated risk factors. The finding of matched
      DNA "fingerprints" among isolates from an immigrant subgroup may reflect
      transmission in the adopted country but could also reflect limited diversity
      among M. tuberculosis organisms within that immigrant community. The authors
      sought to determine which hypothesis is more likely to explain the high frequency
      of matched isolates among Haitian-born tuberculosis patients in Montreal, Quebec,
      Canada. The authors determined the number of different bacterial genotypes in
      this community as compared with other foreign-born tuberculosis patients and
      applied a recently described measure of genetic similarity between M.
      tuberculosis organisms ("genetic distance"). Among 76 Haitian-born tuberculosis
      patients diagnosed during 1996-1998, the authors identified 47 distinct genotypes
      on the basis of standard IS6110 DNA typing and categorical analysis. In genetic
      distance analysis, these 47 genotypes showed as great a genetic diversity as that
      observed among the 191 distinct genotypes identified in 216 other foreign-born
      tuberculosis patients. A mycobacterial "founder effect" is unlikely to account
      for the high proportion of shared isolates among Haitian-born Montrealers. Recent
      transmission remains the most likely explanation.

PMID- 14977648
TI  - Incidence of hepatitis C virus infection and associated risk factors among
      Scottish prison inmates: a cohort study.
AB  - To gauge the incidence of hepatitis C virus (HCV) infection and associated risk
      factors among inmates during their imprisonment, the authors recruited adult
      males in a long-stay Scottish prison into a cohort study between April 1999 and
      October 2000. On two occasions (at 0 and 6 months), saliva was collected for
      anonymous HCV antibody testing and risk behavior data were obtained through a
      self-administered questionnaire. The participation rate was 85% at both initial
      recruitment (612/719) and follow-up (375/441; 171 men were ineligible for follow
      up). For inmates who reported never having injected drugs, ever having injected
      drugs, having injected drugs during follow-up, and having shared needles/syringes
      during follow-up, HCV incidences per 100 person-years of incarceration risk were
      1, 12, 19, and 27, respectively. Ever having injected drugs (relative risk =
      13.0, 95% confidence interval: 1.5, 114.3) and having shared needles/syringes
      during follow-up (relative risk = 9.0, 95% confidence interval: 1.1, 71.7) were
      significantly associated with HCV seroconversion. The effectiveness of existing
      interventions, including the provision of bleach tablets for sterilizing
      injection equipment, was suboptimal. The development of methadone maintenance
      programs in prisons and the creation of drug courts to keep offending drug
      injectors out of prison might help to reduce transmission in this setting.

PMID- 14977649
TI  - Prevalence of constipation: agreement among several criteria and evaluation of
      the diagnostic accuracy of qualifying symptoms and self-reported definition in a
      population-based survey in Spain.
AB  - The aims of this study were to estimate the prevalence of chronic constipation
      and to evaluate the diagnostic accuracy of the symptoms and the self-reported
      definition of constipation. A cross-sectional survey was conducted in the general
      community in 1999. A questionnaire comprising 21 items was developed and mailed
      to a random sample of 489 subjects who were aged between 18 and 65 years and who
      belonged to a Spanish population. In the 349 subjects (71%) responding to the
      questionnaire, the prevalence of self-reported constipation was 29.5% (95%
      confidence interval (CI): 24.9, 34.3) versus 19.2% (95% CI: 15.1, 23.3) and 14.0%
      (95% CI: 10.4, 17.7) based on Rome I and Rome II criteria, respectively.
      Agreement was good between self-reported and Rome I criteria (kappa: 0.68) and
      between Rome I and Rome II criteria (kappa: 0.71), and it was moderate between
      self-reported and Rome II criteria (kappa: 0.55). Female gender was identified to
      be a risk factor for constipation; fiber intake and physical exercise were found
      to be protective factors. Likelihood ratios were higher for the presence of anal
      blockage and straining and for the absence of hard stools. Chronic constipation
      is a highly prevalent problem, especially in women. Different prevalence
      estimates of constipation were observed using different criteria, although
      agreement between them was acceptable. Anal blockage, straining, and hard stools
      show the greatest accuracy for the diagnosis of constipation.

PMID- 14977651
TI  - An evaluation of the apprehension, relocation, and surprise tests for anterior
      shoulder instability.
AB  - BACKGROUND: Although there are many studies describing tests for shoulder
      instability, there are few assessing the validity of these tests in diagnosing
      anterior shoulder instability. PURPOSE: To assess the validity of the
      apprehension, relocation, and surprise tests as predictors of anterior shoulder
      instability. STUDY DESIGN: Retrospective review of prospectively collected data.
      METHODS: Forty-six patients with a clear diagnosis of one of the following
      shoulder disorders were evaluated by four independent, blinded examiners:
      traumatic anterior instability (18), rotator cuff tendinosis (17), posterior
      instability (2), glenohumeral osteoarthritis (4), or multidirectional instability
      (5). Interobserver reliability was also determined. RESULTS: In subjects who had
      a feeling of apprehension on all three tests, the mean positive and negative
      predictive values were 93.6% and 71.9%, respectively. The surprise test was the
      single most accurate test (sensitivity = 63.89%; specificity = 98.91%). An
      improvement in the feeling of apprehension or pain with the relocation test added
      little to the value of the tests. Interobserver reliability was determined to be
      0.83. CONCLUSIONS: and CLINICAL RELEVANCE: The results of this study suggest that
      a positive instability exam on all three tests is highly specific and predictive
      of traumatic anterior glenohumeral instability.

PMID- 14977652
TI  - Biomechanical and histological evaluation of osteochondral transplantation in a
      rabbit model.
AB  - BACKGROUND: Biomechanical and histological properties of osteochondral
      transplantation have not been extensively examined. HYPOTHESIS: Osteochondral
      grafts have properties similar to native articular cartilage. STUDY DESIGN:
      Controlled laboratory study. METHODS: A 2.7 mm (diameter) x 4.0 mm (depth)
      osteochondral defect was created in 17 New Zealand white rabbit knees. An
      osteochondral graft, harvested from the contralateral knee, was transplanted into
      the defect. Eight rabbits were sacrificed each at 6 and 8 weeks. RESULTS: The 12
      week grafts (1213.6 +/- 309.0 N/mm) had significantly higher stiffness than the 6
      week grafts (483.1 +/- 229.1 N/mm; P <.001) and of normal cartilage (774.8 +/-
      117.1 N/mm; P <.003). Stiffness of the 6-week grafts was significantly lower than
      normal cartilage (P <.036). At all time points, full-thickness defects had
      significantly lower stiffness than normal cartilage (P <.001). Histologically,
      transplanted grafts scored significantly higher than the full-thickness defects
      (P <.001). The defects showed inconsistent, fibrocartilage healing. The grafts
      demonstrated cartilage viability, yet with a persistent cleft between the graft
      and host. CONCLUSIONS: Osteochondral transplants undergo increased stiffness in
      the short term, with evidence of structurally intact grafts. CLINICAL RELEVANCE:
      Osteochondral transplantation may be a viable treatment option; however, long
      term investigation on graft function is necessary.

PMID- 14977653
TI  - The effect of graft height mismatch on contact pressure following osteochondral
      grafting: a biomechanical study.
AB  - HYPOTHESIS: Incongruity of the articular cartilage following osteochondral
      transplantation affects surface contact pressure. STUDY DESIGN: An 80 N load was
      applied for 120 seconds to the femoral condyles of 10 swine knees. Contact
      pressures were measured using Fuji prescale film. Seven conditions were tested:
      (1) intact articular surface; (2) 4.5-mm diameter defect; (3) grafted with 4.5-mm
      diameter plug elevated 1 mm above adjacent cartilage; (4) plug elevated 0.5 mm;
      (5) plug flush; (6) plug sunk 0.5 mm below surface; and (7) sunk 1.0 mm.
      CONCLUSIONS: Peak contact pressures were significantly (P <.001) elevated by
      approximately 20% after defect creation and were reduced to normal when plugs
      were flush. There were large and significant (P<.001) increases in pressure with
      plugs elevated 1 and 0.5 mm. Contact pressures with plugs sunk 0.5 and 1 mm were
      significantly (P <.01) higher than intact cartilage but were significantly (P
      <.01) lower than an empty defect. CLINICAL RELEVANCE: Normal contact pressures
      and patterns can be duplicated with flush articular surface grafts. However,
      small incongruities, particularly when the plug is elevated, can lead to
      significantly increased pressure. This reinforces the importance of articular
      surface congruity in the initial biomechanical state following osteochondral
      implantation.

PMID- 14977654
TI  - Use of bone marrow stromal cells for tendon graft-to-bone healing: histological
      and immunohistochemical studies in a rabbit model.
AB  - BACKGROUND: Despite increasing attention on the issue of tendon-to-bone
      integration, there has been no animal study on the use of cell therapy for
      promoting the insertion healing of tendon to bone. PURPOSE: To determine the
      efficacy of using a large number of bone marrow stromal cells (bMSCs) to enhance
      tendon-to-bone healing. STUDY DESIGN: Controlled laboratory study. METHODS: The
      hallucis longus tendons were translated into 2.5-mm diameter calcaneal bone
      tunnels in a New Zealand white rabbit model. The bone tunnels were treated with
      or without bMSCs. Three specimens from each group were harvested at 2, 4, and 6
      weeks postoperatively and evaluated by conventional histological and
      immunohistochemical methods. RESULTS: At 4 weeks, the specimens with bMSCs
      exhibited more perpendicular collagen fiber formation and increased proliferation
      of cartilage-like cells, which was indicated by positive collagen type-II immuno
      staining of the tendon-bone interface. In contrast, the specimens without bMSCs
      demonstrated progressive maturation and reorganization of fibrous tissue aligned
      along the load axis. CONCLUSION: Introduction of a large number of bone marrow
      stromal cells to the bone tunnel have shown to improve the insertion healing of
      tendon to bone in a rabbit model through formation of fibrocartilagenous
      attachment at early time points.

PMID- 14977655
TI  - Shoulder injuries to quarterbacks in the national football league.
AB  - BACKGROUND: Quarterbacks are at risk for shoulder injury secondary to both the
      throwing motion as well as from contact injury. OBJECTIVE: To delineate the
      incidence and etiology of shoulder injuries to quarterbacks in the National
      Football League (NFL). METHODS: Using the NFL Injury Surveillance System
      (NFLISS), all reported injuries to quarterbacks between 1980 and 2001 were
      identified. RESULTS: A total of 1534 quarterback injuries were identified with a
      mean of 18.8 and a median of 6.0 days of playing time lost. The majority of these
      injuries occurred during a game (83.8%). Passing plays were responsible for 77.4%
      of all quarterback-related injuries. Shoulder injuries were the second most
      common injury reported (233 or 15.2%), following closely behind head injuries
      (15.4%). Direct trauma was responsible for 82.3% of the injuries, with
      acromioclavicular joint sprains being the most common injury overall (40%).
      Overuse injuries were responsible for 14% of the injuries, the most common being
      rotator cuff tendinitis (6.1%) followed by biceps tendinitis (3.5%). CONCLUSION:
      In this review, the vast majority of shoulder injuries in quarterbacks occurred
      as a result of direct trauma (82.3%), and less than 15% were overuse injuries
      resulting from the actual throwing motion.

PMID- 14977656
TI  - Arthroscopic drilling with debridement of remaining cartilage for osteochondral
      lesions of the talar dome in unstable ankles.
AB  - BACKGROUND: Arthroscopic examination has shown that the regenerative cartilage
      that appears after arthroscopic drilling for the treatment of osteochondral
      lesions of the talar dome does not always cover the cartilage defect
      sufficiently. HYPOTHESIS: The remaining degenerative cartilage at the lesions may
      obstruct the healing of the articular cartilage. STUDY DESIGN: Prospective cohort
      study. METHODS: Thirty-nine patients underwent arthroscopic drilling that kept
      the remaining cartilage at the lesion (group A), and 30 patients underwent
      arthroscopic drilling that removed the remaining cartilage at the lesion (group
      B). At 1 year after the operation, we performed ankle arthroscopy to evaluate the
      cartilage condition. RESULTS: The arthroscopic findings revealed that in group A,
      11 cases (28.2%) were improved, 12 cases (30.8%) were unchanged, and 16 cases
      (41.0%) had deteriorated; in group B, 27 cases (93.1%) were improved and 2 cases
      were unchanged. There were significant differences between group A and group B in
      the rate of cases whose cartilage condition was seen to improve under
      arthroscopic examination (P < 0.0001). CONCLUSIONS: The study shows that in the
      treatment of osteochondral lesions of the talar dome, the removing of the
      remaining degenerative cartilage may be of some benefit in the treatment of these
      lesions.

PMID- 14977657
TI  - The posteromedial corner of the knee: medial-sided injury patterns revisited.
AB  - BACKGROUND: Medial-sided knee injury patterns have been poorly defined in the
      available literature. The lack of definition can be attributed to the differing
      anatomic perspectives of physician authors and the functional significance they
      assigned to the posteromedial structures of the knee. HYPOTHESIS: Many so-called
      medial collateral ligament injuries can involve significant damage to the
      posteromedial corner structures that may not be appreciated. STUDY DESIGN:
      Retrospective cohort study. METHOD: The authors reviewed the charts of 93
      patients (93 knees) with operatively treated isolated and combined medial-sided
      knee injuries and described the associated medial injury patterns. RESULTS:
      Ninety-nine percent of the knees were found to have an injury of the posterior
      oblique ligament. In the series, 70% of the knees also had an injury of the
      semimembranosus capsular attachment, and 30% were found to have complete
      peripheral detachment of the meniscus. Injury to the posterior oblique ligament
      was the common injury, but other sites of disruption capable of disabling this
      dynamic meniscocapsular complex were present. CONCLUSIONS: Before assigning
      function to the various posteromedial structures of the knee, we must better
      define medial-sided injury patterns, the purpose of the current work. From this
      review of medial-sided injuries in this series of patients, the authors have come
      to realize that a subgroup of these knee injuries involves injuries to the
      posteromedial structures that are under-appreciated.

PMID- 14977658
TI  - Posterior cruciate ligament reconstruction using single-bundle patella tendon
      graft with tibial inlay fixation: 2- to 10-year follow-up.
AB  - PURPOSE: Reconstruction of the posterior cruciate ligament (PCL) using the tibial
      inlay fixation has been reported as an alternative to the transtibial tunnel
      technique. Previous failures in PCL reconstruction and early reports raising
      potential biomechanical and clinical advantages have spurred interest in this
      technique. The purpose of this study was to evaluate the minimum 2-year results
      of PCL reconstruction using a single-bundle bone-patellar tendon-bone graft and
      tibial inlay fixation. METHODS: The authors prospectively studied 44 patients
      having isolated or combined PCL reconstruction using the direct tibial inlay
      fixation technique. The study period was from 1991 to 2001. Two-year minimum
      follow-up was 93% (41/44) and averaged 39.4 months. These 41 patients comprised
      the study group. Thirty-one patients were male and 10 patients were female;
      average age was 28 years. There were 35 primary and 6 revision reconstructions.
      Surgery was performed in the acute or subacute setting (<8 weeks) in 34% (14/41)
      and chronic setting in 66% (27/41). Combined reconstructions involving the
      posterolateral corner, anterior cruciate ligament (ACL), or medial collateral
      ligament (MCL) were done in 85% (35/41). In all patients, preoperative posterior
      drawer (PD) examination demonstrated greater than 12 mm posterior translation.
      All PCL reconstructions were performed with bone-patellar tendon-bone graft,
      which was 12 to 18 mm in width (16 autograft; 25 allograft). Wider tendon grafts
      were prepared from the allografts and tubularized to fit through an 11-mm tunnel.
      All patients were evaluated with preoperative and postoperative examination and x
      rays. Final follow-up International Knee Documentation Committee (IKDC)
      subjective evaluation, final follow-up IKDC objective evaluation, and final
      follow-up Telos stress radiography were performed in all patients. RESULTS:
      Postoperative PD examination demonstrated the following: 0 (normal) in 9
      patients, 1+ in 25 patients, 2+ in 7 patients, and none >2+, as compared to
      preoperative PD 3+ or greater in all patients in this report. No patient had <12
      mm PD preoperatively. Mean improvement in PD was >2 grades of translation as
      compared to preoperative exam. Forty of forty-one demonstrated a solid endpoint
      on clinical PD testing. Final follow-up Telos stress radiography with 25 kg
      posterior load applied at 80 degrees to 90 degrees of flexion demonstrated
      average side-to-side difference of 4.11 mm (-2 to 10 mm). Average flexion loss
      was 4 degrees (0-15 degrees ). None lost extension. Preoperative IKDC objective
      evaluation rated all knees as severely abnormal based on instability. Final
      follow-up objective IKDC evaluation distribution was as follows: A, 4 knees; B,
      24 knees; C, 11 knees; and D, 2 knees, as compared to all 41 D preoperatively.
      Average final follow-up IKDC subjective score was 75.1 (20-100). When assessing
      final follow-up stability with Telos stress radiography, primary cases were
      significantly more stable than revision cases (P <.05). There was no difference
      in stability when comparing allograft versus autograft, but improved IKDC scores
      were seen with allograft (P <.05). There was a trend for combined reconstructions
      to be more stable than isolated reconstructions. All patients evaluated their
      knee as improved or greatly improved and would repeat the procedure. CONCLUSIONS:
      Reconstruction of the PCL-deficient knee with severe posterior laxity is a
      challenging surgical problem, as combined instability patterns frequently coexist
      (85% in this study). When appropriate combined reconstructions or primary repair
      is used, PCL reconstruction with autologous or allograft bone-patellar tendon
      bone graft using tibial inlay fixation was shown to be a successful technique at
      2- to 10-year follow-up. Based on their initial experience with this technique
      and previous experience with open and arthroscopic techniques using a transtibial
      tunnel, the authors continue to use the tibial inlay technique as their preferred
      technique for isolated or combined reconstruction of the PCL.

PMID- 14977659
TI  - Arthroscopic posterior cruciate ligament reconstruction with quadriceps tendon
      autograft: minimal 3 years follow-up.
AB  - BACKGROUND: Various autografts or allografts have been used for posterior
      cruciate ligament (PCL) reconstruction. Quadriceps tendon-patellar bone autograft
      is considered a good graft choice. HYPOTHESIS: Quadriceps tendon-patellar bone
      graft for PCL reconstruction can achieve a satisfactory clinical outcome after 3
      years postoperatively. STUDY DESIGN: Retrospective review of prospectively
      collected data. METHODS: From 1996, the graft has been used in 32 patients.
      Twenty-nine patients with a minimum of 3 years of follow-up were analyzed.
      RESULTS: Twenty-four (83%) patients achieved good or excellent results by Lysholm
      knee rating. Sixteen (55%) patients could return to moderate or strenuous
      activity. Twenty-five (86%) patients had ligament laxity of less than 5 mm.
      Twenty-four (83%) patients were rated as normal or nearly normal by International
      Knee Documentation Committee (IKDC) guidelines. Twenty-four (83%) and 26 (90%)
      patients could achieve recovery of extensor and flexor muscle strength to 80% or
      more of normal knee, respectively. A statistically significant difference exists
      in thigh girth difference, extensor strength, and flexor strength before and
      after reconstruction. CONCLUSION: Our study revealed satisfactory clinical
      subjective and objective results at a minimum 3 years follow-up. Quadriceps
      tendon autograft has the advantage of being self-available, a relatively easier
      arthroscopic technique, and having a suitable size, making it an acceptable graft
      choice for PCL reconstruction.

PMID- 14977660
TI  - What really happens during the Lachman test? A dynamic MRI analysis of
      tibiofemoral motion.
AB  - BACKGROUND: The Lachman test is the most reliable clinical test for diagnosing
      rupture of the anterior cruciate ligament (ACL). It is generally believed that
      the lateral side contributes more than the medial side to anterior tibial
      translation, but this has never been convincingly proven. The MRI study presented
      in this article addresses this issue. HYPOTHESIS: The lateral side of the ACL
      deficient knee contributes more than the medial side to anterior tibial
      translation. STUDY DESIGN: Prospective cohort study. METHODS: The Lachman test
      and the radiologic Lachman test were performed on 10 patients with isolated
      rupture of the ACL while the knee was scanned dynamically using open-access
      magnetic resonance imaging. The amount of movement in the midmedial and
      midlateral compartments of both the contralateral normal knee and the ACL
      deficient knee was measured. RESULTS: In both normal and ACL-deficient knees, the
      lateral compartment contributes more than the medial to anterior translation of
      the tibia. Rupture of the ACL leads to increased laxity in both medial and
      lateral compartments with a statistically significant greater contribution from
      the lateral side. CONCLUSION: Rupture of the ACL leads to increased anterior
      tibial translation coupled with tibial internal rotation.

PMID- 14977661
TI  - Effects of increasing tibial slope on the biomechanics of the knee.
AB  - PURPOSE: To determine the effects of increasing anterior-posterior (A-P) tibial
      slope on knee kinematics and in situ forces in the cruciate ligaments. METHODS:
      Ten cadaveric knees were studied using a robotic testing system using three
      loading conditions: (1) 200 N axial compression; (2) 134 N A-P tibial load; and
      (3) combined 200 N axial and 134 N A-P loads. Resulting knee kinematics were
      determined before and after a 5-mm anterior opening wedge osteotomy. Resulting in
      situ forces in each cruciate ligament were determined. RESULTS: Tibial slope was
      increased from 8.8 +/- 1.8 degrees to 13.2 +/- 2.1 degrees, causing an anterior
      shift in the resting position of the tibia relative to the femur up to 3.6 +/-
      1.4 mm. Under axial compression, the osteotomy caused a significant anterior
      tibial translation up to 1.9 +/- 2.5 mm (90 degrees ). Under A-P and combined
      loads, no differences were detected in A-P translation or in situ forces in the
      cruciates (intact versus osteotomy). CONCLUSIONS: Results suggest that small
      increases in tibial slope do not affect A-P translations or in situ forces in the
      cruciate ligaments. However, increasing slope causes an anterior shift in tibial
      resting position that is accentuated under axial loads. This suggests that
      increasing tibial slope may be beneficial in reducing tibial sag in a PCL
      deficient knee, whereas decreasing slope may be protective in an ACL-deficient
      knee.

PMID- 14977662
TI  - The effect of creatine supplementation on strength recovery after anterior
      cruciate ligament (ACL) reconstruction: a randomized, placebo-controlled, double
      blind trial.
AB  - BACKGROUND: Creatine supplementation has been shown to augment training-induced
      strength gains. The purpose of this study was to examine the effect of creatine
      supplementation on recovery of muscle strength after anterior cruciate ligament
      (ACL) reconstruction. HYPOTHESIS: Creatine supplementation will facilitate
      strength gains after ACL reconstruction. STUDY DESIGN: Double-blind, prospective,
      and randomized clinical trial. METHODS: Sixty patients were randomized into
      creatine or placebo groups. Quadriceps and hamstring strength and power were
      measured isokinetically. Hip flexor, abductor, and adductor strengths were
      measured with a handheld dynamometer prior to surgery and at 6 weeks, 12 weeks,
      or 6 months after surgery. RESULTS: From 6 weeks to 12 weeks after surgery, there
      were significant increases in strength on the involved side for knee extension
      (47%), knee flexion (27%), hip flexion (20%), hip abduction (9%), and hip
      adduction (17%). These strength improvements were unaffected by creatine
      supplementation with similar effects in the creatine and placebo groups. From 6
      weeks to 12 weeks after surgery, there were significant increases in power on the
      involved side for knee extension (46%) and knee flexion (26%), but these effects
      were not affected by creatine supplementation. At 6 months, creatine
      supplementation did not affect outcome as measured by the single leg hop test for
      distance or the knee outcome score. CONCLUSIONS: The results demonstrate that
      patients do not benefit from creatine supplementation during the first 12 weeks
      of rehabilitation after ACL reconstruction.

PMID- 14977663
TI  - The accessory anteroinferior tibiofibular ligament as a cause of talar
      impingement: a cadaveric study.
AB  - BACKGROUND: A distal fascicle of the anteroinferior tibiofibular ligament has
      been reported as a possible cause of anterolateral ankle impingement. HYPOTHESIS:
      This fascicle represents an independent accessory ligament in the anterior aspect
      of the inferior tibiofibular syndesmosis. STUDY DESIGN: Descriptive anatomical
      study. METHODS: The inferior tibiofibular syndesmosis was exposed in 24 fresh
      frozen cadaveric ankles. Morphological characteristics of the inferior
      tibiofibular ligaments and interactions between the anterior ligaments and the
      talus were investigated in different degrees of ankle motion. RESULTS: A separate
      accessory anterior ligament was identified in 22 specimens. Its orientation was
      parallel and distal to the anterior tibiofibular ligament, from which it was
      separated by a fibrofatty septum. Its length ranged from 17 to 22 mm, its
      thickness from 1 to 2 mm, and its width from 3 to 5 mm. Impingement of this
      ligament against the talar dome was documented in all specimens in neutral ankle
      position, with bending of the ligamentous bands in dorsiflexion. Distraction
      maneuvers reproducing traction during arthroscopic approaches relieved contact.
      CONCLUSIONS: An accessory anteroinferior tibiofibular ligament with distinct
      anatomical features was recognized. CLINICAL RELEVANCE: Based on its increased
      incidence in the cadaver ankles, the accessory ligament reflects a normal
      anatomical finding. Nevertheless, it could lead to anterolateral impingement in
      cases with coexistent ankle instability.

PMID- 14977664
TI  - A prospective cohort study of injury incidence and risk factors in North Carolina
      high school competitive cheerleaders.
AB  - BACKGROUND: Cheerleaders suffer nearly half of catastrophic injuries observed in
      female scholastic athletes in the United States. However, incidence of
      noncatastrophic injury in this population has not been described. HYPOTHESIS:
      Coach, athlete, and injury circumstance variables may predict the injury rate
      among cheerleaders. STUDY DESIGN: Prospective cohort. METHODS: The authors
      investigated injury incidence in a sample of North Carolina female cheerleaders
      who competed inter-scholastically from 1996 to 1999. Injury, exposure, and
      demographic data were collected from squads that participated in the North
      Carolina High School Athletic Injury Study. RESULTS: Cheerleaders suffered 133
      injuries during 1701 athlete seasons. More than 21% of the injuries were ankle
      sprains. The injury rate was 8.7; the 95% confidence interval (CI) was 6.5 to
      11.7 per 10,000 athlete exposures. In a multivariate Poisson regression model,
      cheerleaders supervised by coaches with the most education, qualifications, and
      training (coach EQT) had a nearly 50% reduction in injury risk (rate ratio [RR],
      0.5; 95% CI, 0.3-0.9), and cheerleaders supervised by coaches with medium coach
      EQT had a nearly 40% reduction in injury risk (RR = 0.6; 95% CI, 0.3-1.2)
      compared to cheerleaders supervised by coaches with low coach EQT.

PMID- 14977665
TI  - A new technique: in vitro suture anchor fixation has superior yield strength to
      bone tunnel fixation for distal biceps tendon repair.
AB  - BACKGROUND: Suture anchor and bone tunnel fixations are used for distal biceps
      tendon repairs and have not been compared. HYPOTHESIS: Suture anchor fixation is
      equal or superior to bone tunnel fixation. STUDY DESIGN: Randomized controlled in
      vitro study. METHODS: A new fixation technique was compared to traditional bone
      tunnel fixation of distal biceps tendon ruptures between randomly selected sides
      of nine matched-pair, fresh-frozen elbow specimens from cadaveric donors (mean
      age = 74.7 years). Bone densities were determined. The distal biceps tendon was
      attached to the actuator of a servohydraulic load frame and loaded to tensile
      failure at a constant rate of 4 mm/sec. Bone density, sex, age, side, tuberosity
      area, repair, failure type, repair stiffness, and yield strength were compared.
      RESULTS: Superior yield strength of suture anchor fixation (263 N) compared to
      bone tunnel fixation (203 N) (P = 0.0233) were demonstrated. When suture anchor
      fixation failure (1 of 9) occurred, the matched pair also failed. CONCLUSION:
      Suture anchor fixation offers an equal if not superior alternative to bone tunnel
      fixation for repair of the distal biceps tendon in the specimens tested. CLINICAL
      RELEVANCE: Suture anchor fixation may be used for distal biceps tendon repairs.

PMID- 14977666
TI  - Interference screw fixation of soft tissue grafts in anterior cruciate ligament
      reconstruction: part 1: effect of tunnel compaction by serial dilators versus
      extraction drilling on the initial fixation strength.
AB  - BACKGROUND: Compaction of the bone-tunnel walls by serial dilation is believed to
      enhance the interference screw fixation strength of the soft tissue grafts in
      anterior cruciate ligament (ACL) reconstruction. HYPOTHESIS: Serial dilation
      enhances the fixation strength of soft tissue grafts in ACL reconstruction over
      extraction drilling. STUDY DESIGN: Randomized experimental study. METHODS:
      Initial fixation strength of the doubled anterior tibialis tendon grafts (fixed
      with a bioabsorbable interference screw) was assessed in 21 pairs of human
      cadaver tibiae with either serially dilated or extraction-drilled bone tunnels.
      The specimens were subjected to a cyclic-loading test, and those surviving were
      then tested using the single-cycle load-to-failure test. RESULTS: During the
      cyclic-loading test, there were 3 fixation failures in the serially dilated and 6
      failures in the extraction-drilled specimens but no significant stiffness or
      displacement differences between the groups. In the subsequent load-to-failure
      test, the average yield loads were 473 +/- 110 N and 480 +/- 115 N for the 2
      groups respectively (P =.97) and no difference with regard to stiffness or mode
      of failure. CONCLUSIONS: Serial dilation does not increase the strength of
      interference fixation of soft tissue grafts in ACL reconstruction over extraction
      drilling. CLINICAL RELEVANCE: The results of this experiment do not support the
      use of serial dilators in ACL reconstruction.

PMID- 14977667
TI  - Interference screw fixation of soft tissue grafts in anterior cruciate ligament
      reconstruction: part 2: effect of preconditioning on graft tension during and
      after screw insertion.
AB  - BACKGROUND: Preconditioning of tendon grafts is believed to eliminate natural
      viscoelasticity of the tendons and prevent knee laxity after anterior cruciate
      ligament (ACL) reconstruction. HYPOTHESIS: Preconditioned ACL grafts maintain
      their initially set tension. STUDY DESIGN: Randomized experimental study.
      METHODS: Forty-two human anterior tibialis (AT) tendon grafts were subjected to
      either no preconditioning (group 1), cyclic preconditioning (group 2), or
      isometric preconditioning (group 3). The residual graft tension was then recorded
      immediately after the application of an initial graft tension of 80 N and
      fixation into tibia with an interference screw, as well as 10 minutes later. In
      another experiment, the residual graft tension was recorded 1, 10, and 60 minutes
      after 10 AT and quadrupled hamstring tendon (HT) grafts alone (no fixation) had
      been subjected to isometric preconditioning (80 N). RESULTS: Immediately after
      screw insertion, the residual (AT) graft tensions were 79 +/- 19 N, 100 +/- 17 N,
      and 102 +/- 15 N in groups 1 through 3, respectively. Ten minutes later, the
      corresponding values were 49 +/- 16 N, 60 +/- 11 N, and 64 +/- 12 N. For the AT
      and HT grafts alone, the residual graft tensions were 67 +/- 2 N and 67 +/- 2 N,
      45 +/- 2 N and 46 +/- 4 N, and 29 +/- 3 N and 34 +/- 5 N at 1, 10, and 60
      minutes, respectively. CONCLUSIONS: A steady decrease (-60% within 60 minutes
      after initial tensioning) occurs in the initially set tension of the soft tissue
      ACL grafts. CLINICAL RELEVANCE: Clinically applicable preconditioning protocols
      cannot eliminate the intrinsic viscoelasticity from ACL soft tissue grafts, and
      thus, the reasonableness of preconditioning per se is questioned in ACL
      reconstruction.

PMID- 14977668
TI  - Proprioception of the shoulder joint after surgical repair for Instability: a
      long-term follow-up study.
AB  - BACKGROUND: Proprioceptive capabilities play an important role in stability of
      the shoulder joint. HYPOTHESIS: Decreased proprioceptive capabilities can improve
      by surgical repair of shoulder instability. STUDY DESIGN: Prospective long-term
      study. METHODS: The proprioceptive capabilities of 14 patients with recurrent
      anterior shoulder instability were examined preoperative and with a minimum
      follow-up of 5 years postoperative using the angle reproduction test. The
      patients' data were compared to a healthy control group. RESULTS: The joint
      position sense improved significantly in abduction, flexion, and rotation (P
      <.05). The preoperative difference from the target joint position was 9.3 degrees
      (SD, 4.6 degrees ) for the summarized positions in abduction, 9.1 degrees (SD,
      4.5 degrees ) in flexion, and 10.1 degrees (SD, 5.1 degrees ) in rotation.
      Postoperatively, it improved to 5.6 degrees (SD, 2.9 degrees ) in abduction, 5.6
      degrees (SD, 2.7 degrees ) in flexion, and 5.0 degrees (SD, 1.8 degrees ) in
      rotation. The joint position sense of the uninvolved contralateral shoulder
      improved too. CONCLUSIONS: Five years after surgical repair for shoulder
      instability, the joint position sense improved significantly, to a level of
      normal, healthy shoulders.

PMID- 14977669
TI  - Triceps tendon ruptures in professional football players.
AB  - BACKGROUND: Distal rupture of the triceps tendon is a rare injury, and treatment
      guidelines are not well established. HYPOTHESIS: Football players with triceps
      tendon ruptures will be able to return to their sport with minimal functional
      deficits. STUDY DESIGN: Uncontrolled retrospective review. METHODS: Twenty-one
      partial and complete ruptures of the triceps tendon were identified in 19
      National Football League players over a period of 6 years. Team physicians
      retrospectively reviewed training room, clinical, and operative notes for each of
      these players. RESULTS: Most of the injured players were linemen. The most common
      mechanism of injury was an eccentric load to a contracting triceps. Seven players
      had prodromal symptoms prior to injury, and 5 had received a cortisone injection.
      Eleven elbows with complete tears underwent surgical repair. Of 10 players with
      partial tears, 6 healed without surgery. One player suffered a subsequent
      complete tear requiring surgery, and 3 with residual pain and weakness underwent
      surgical repair following the season. Two surgical complications occurred, both
      requiring a second operation. All of the players but 1 returned to play at least
      one season of professional football after their injury. CONCLUSIONS: Partial
      triceps tendon ruptures can heal without functional deficit. Surgical repair for
      complete ruptures generally produces good functional results and allows return to
      play.

PMID- 14977670
TI  - Inflammatory response of human tendon fibroblasts to cyclic mechanical
      stretching.
AB  - BACKGROUND: The cellular and molecular mechanisms for the development of
      tendinopathy are not clear, but inflammatory mediators produced by tendon
      fibroblasts in response to repetitive mechanical loading may be an important
      factor. HYPOTHESES: (1) Cyclic stretching of tendon fibroblasts affects the
      production of leukotriene B(4) and the expression of 5-lipoxygenase; and (2) the
      production level of leukotriene B(4) is inversely related to that of
      prostaglandin E(2). STUDY DESIGN: Controlled laboratory study. METHODS: Human
      patellar tendon fibroblasts were uniaxially stretched in the presence of
      indomethacin (25 micro M) or MK-886 (10 micro M). After stretching for 4 hours,
      followed by 4 hours rest, levels of prostaglandin E(2), leukotriene B(4), and
      expression of 5-lipoxygenase were measured. RESULTS: Stretched tendon fibroblasts
      increased the levels of leukotriene B(4) but did not appreciably change the
      expression of 5-lipoxygenase. Indomethacin decreased the cellular production of
      prostaglandin E(2) but caused increased leukotriene B(4) levels. MK-886 caused
      decreased production of leukotriene B(4) but increased production of
      prostaglandin E(2). CONCLUSIONS: Cyclic stretching of human tendon fibroblasts
      increases the production of prostaglandin E(2) and leukotriene B(4). Blocking
      prostaglandin E(2) production leads to increased leukotriene B(4) levels and vice
      versa. CLINICAL RELEVANCE: The use of nonsteroidal anti-inflammatory drugs for
      the treatment of tendon inflammation might increase the levels of leukotriene
      B(4) within the tendon, potentially contributing to the development of
      tendinopathy.

PMID- 14977672
TI  - Fractures in the collegiate athlete.
AB  - PURPOSE: To determine the demographics and incidence of fractures in collegiate
      athletes. STUDY DESIGN: Retrospective review of prospectively collected data.
      METHODS: Division I collegiate athletes who sustained a fracture while enrolled
      at the university from 1986 to 2000 were identified through training room
      records. Type and location of fracture, sport, gender, age, position, height, and
      weight were recorded and analyzed. Team information was obtained from athletic
      department records and was used to calculate incidence. RESULTS: Between 1986 and
      2000, 5900 Division I athletes at our institution sustained 349 primary fractures
      (5.9%). By gender, the incidence did not differ significantly between males and
      females (P =.236), except in water polo where the men sustained significantly
      more fractures. By type, females sustained significantly more stress fractures (P
      =.001) than males. Overall, by location, the hand contributed the greatest number
      of total fractures. By sport, the incidence rate was highest in basketball
      (0.081) for male athletes and in gymnastics (0.069) for female athletes. The
      incidence of a second fracture during the study period was twice the rate of the
      first fracture. CONCLUSIONS: As expected, athletes participating in contact
      sports contributed the greatest number of fractures. Participation in basketball
      for men and in gymnastics for women posed the greatest risk. Female athletes
      sustained significantly more stress fractures.

PMID- 14977671
TI  - Intra-articular knee temperature changes: ice versus cryotherapy device.
AB  - BACKGROUND: Cryotherapy is commonly applied without research documenting the
      intra-articular (IA) temperature changes or subject discomfort between ice and a
      cryotherapy device. HYPOTHESIS: The null hypothesis is that no difference would
      be observed in IA temperature decline or subject tolerance between ice and the
      cryotherapy device in normal knees. STUDY DESIGN: Prospective, within-subject
      controlled clinical trial. METHODS: Twelve subjects had IA temperature in
      suprapatellar pouch and skin recorded bilaterally after application of
      cryotherapy versus ice. Subject tolerance was recorded by 10-cm visual analog
      scale (VAS). Statistical evaluation was by Spearman's correlation analysis and
      paired, nonparametric Wilcoxon's signed rank test. RESULTS: Both significantly
      lowered (P < 0.001) skin and IA temperature with median decreases
      (ice/cryotherapy) at 30 (3.3 degrees C/2.2 degrees C), 60 (12.8 degrees C/7.1
      degrees C), and 90 (15.2 degrees C/9.7 degrees C) minutes. However, ice lowered
      the IA temperature significantly more than the cryotherapy device (P < 0.001) and
      was more painful by VAS at 30 and 60 minutes (P < 0.01). CONCLUSIONS: Both
      methods produced large declines in skin and IA temperatures. However, ice was
      more effective yet resulted in higher pain scores. The authors hypothesize that
      IA temperatures below a threshold are associated with increased perceived pain.

PMID- 14977673
TI  - Near infrared spectroscopy in the diagnosis of chronic exertional compartment
      syndrome.
AB  - BACKGROUND: Patients with chronic exertional compartment syndrome (CECS)
      experience pain during exercise. An abnormal increase in intracompartmental
      pressure (ICP) leads to impaired local tissue perfusion resulting in ischemia and
      pain. At cessation of exercise, pain subsides. Diagnosis is confirmed through
      postexercise ICP. Near infrared spectroscopy (NIRS) can measure tissue oxygen
      saturation (StO(2)) noninvasively. HYPOTHESIS: NIRS can diagnose CECS by showing
      tissue deoxygenation. STUDY DESIGN: Prospective, nonrandomized clinical trial.
      METHOD: Volunteers completed a standardized exercise protocol. Those suspected of
      CECS did so preoperatively and postoperatively. StO(2) and ICP were monitored.
      Data were compared between volunteers and patients and prefasciotomy and
      postfasciotomy. RESULTS: Significant differences between the StO(2) values of
      volunteers and patients with CECS were found. Average peak exercise StO(2) value
      for those with CECS was lower than for the healthy (27 versus 56, P <.05).
      Patients showed more absolute and percentage change between baseline and peak
      exercise StO(2) (absolute: 60 versus 35, P <.05; percentage: 67 versus 38, P
      <.05). StO(2) values in legs with confirmed CECS returned to normal range
      postfasciotomy. All changes differed significantly with preoperative values.
      CONCLUSION: StO(2) can distinguish healthy from diseased legs. This study
      provides evidence supporting NIRS as a noninvasive, painless alternative to ICP
      in the diagnosis of CECS.

PMID- 14977674
TI  - Strain behavior of the distal achilles tendon: implications for insertional
      achilles tendinopathy.
AB  - BACKGROUND: The changes associated with Achilles insertional tendinopathy (AIT)
      are seen in the anterior portion of the Achilles tendon near its calcaneal
      insertion. Strain behavior of this portion of the tendon was evaluated.
      HYPOTHESIS: The highest strains are in the anterior portion of the tendon. STUDY
      DESIGN: Controlled laboratory study. METHODS: Six cadaveric legs were tested.
      While moving through a functional range of ankle motion, strains in five
      different regions of the tendon insertion were tested. First, the load on the
      tendon was increased from 30 to 170 N in the starting, plantar flexed position.
      Then, the ankle was moved from a plantar flexed position into dorsiflexion.
      RESULTS: Strains in the posterior sites increased significantly (P < 0.001) as
      the movement into dorsiflexion occurred. This was significantly (P < 0.01)
      different than the anterior sites, which showed a trend toward decreasing strain.
      CONCLUSIONS: Although the anterior portion of the Achilles tendon is generally
      affected in AIT, relative strain shielding is seen in this portion of the tendon.
      These findings suggest that the role of repetitive tensile loads in the causation
      of AIT is more complex than often described. CLINICAL RELEVANCE: These findings
      may explain the variable therapeutic response following measures aimed at
      decreasing tensile loads on the tendon.

PMID- 14977675
TI  - Conservative treatment of lateral epicondylitis: brace versus physical therapy or
      a combination of both-a randomized clinical trial.
AB  - BACKGROUND: The authors evaluated the effectiveness of brace-only treatment,
      physical therapy, and the combination of these for patients with tennis elbow.
      METHODS: Patients were randomized over 3 groups: brace-only treatment, physical
      therapy, and the combination of these. Main outcome measures were success rate,
      severity of complaints, pain, disability, and satisfaction. Data were analyzed
      using both intention-to-treat and per-protocol analyses. Follow-up was 1 year.
      RESULTS: A total of 180 patients were randomized. Physical therapy was superior
      to brace only at 6 weeks for pain, disability, and satisfaction. Contrarily,
      brace-only treatment was superior on ability of daily activities. Combination
      treatment was superior to brace on severity of complaints, disability, and
      satisfaction. At 26 weeks and 52 weeks, no significant differences were
      identified. CONCLUSION: Conflicting results were found. Brace treatment might be
      useful as initial therapy. Combination therapy has no additional advantage
      compared to physical therapy but is superior to brace only for the short term.

PMID- 14977676
TI  - The surgical treatment of external coxa saltans (the snapping hip) by Z-plasty of
      the iliotibial band.
AB  - PURPOSE: A snapping hip (coxa saltans) secondary to a tight iliotibial band
      rarely needs surgical intervention. The purpose of this study is to present the
      surgical results of refractory external-type snapping hip by Z-plasty of the
      iliotibial band. MATERIALS AND METHODS: Nine symptomatic snapping hips in 8
      consecutive patients (1 bilateral) from August 1997 through March 2002 who
      underwent an iliotibial band Z-plasty were reviewed. RESULTS: Eight of the 9 hips
      were in active-duty military and 1 was a civilian, with an average age of 25.6
      years (range, 21 to 38 years). Mean duration of symptoms prior to surgical
      intervention was 25.2 months (range, 16 to 39 months) with an average follow-up
      of 22.9 months (range, 7 to 38 months). All patients had complete resolution of
      the snapping hip, and all but 1 returned to full unrestricted activities. The 1
      failure had persistent groin pain but no residual snapping. CONCLUSIONS: Patients
      with snapping hip of the iliotibial band refractory to conservative treatment are
      rare. The surgical results of Z-plasty are excellent and predictable. Careful
      screening is necessary to preclude other confounding diagnoses. Z-plasty is
      recommended as an effective surgical treatment of the refractory snapping hip
      secondary to iliotibial band tightness.

PMID- 14977677
TI  - Aggressive quadriceps loading can induce noncontact anterior cruciate ligament
      injury.
AB  - BACKGROUND: The force responsible for noncontact anterior cruciate ligament (ACL)
      injuries remains controversial. The patella tendon to tibial shaft angle causes
      an anterior tibial shear force with quadriceps activation. HYPOTHESIS: An
      aggressive quadriceps contraction can injure the ACL. METHODS: The authors
      characterized noncontact ACL injury and kinematics with aggressive quadriceps
      loading. Thirteen fresh-frozen knees were potted in a jig held in 20 degrees of
      flexion while a 4500 N quadriceps contraction was simulated. Knee kinematics were
      recorded. A KT-1000 arthrometer and a simulated active quadriceps test assessed
      anterior displacement. Statistics were performed using paired t tests and 1-way
      analysis of variance. RESULTS: Kinematics revealed the following mean values:
      anterior displacement, 19.5 mm; valgus, 2.3 degrees; and internal rotation, 5.5
      degrees. Mean KT-1000 and active quadriceps test differences were 4.0 mm and 2.7
      mm, respectively (statistically significant P =.002 and P =.002). Six knees
      showed gross ACL injury at the femoral insertion. Based on ACL injury, KT-1000
      differences were statistically significant (P =.029). CONCLUSIONS: Aggressive
      quadriceps loading, with the knee in slight flexion, produces significant
      anterior tibial translation and ACL injury. This suggests that the quadriceps is
      the intrinsic force in noncontact ACL injuries, producing a model for further
      investigation.

PMID- 14977678
TI  - Relative balance of serratus anterior and upper trapezius muscle activity during
      push-up exercises.
AB  - BACKGROUND: Serratus anterior strengthening is used in prevention and treatment
      programs for poor scapular control. In certain clinical cases, exercises
      substantially activating the serratus with minimal upper trapezius activation are
      preferred. HYPOTHESIS: The standard push-up plus would show both the highest
      serratus anterior activation and lowest upper trapezius/ serratus ratios for both
      groups and all phases. STUDY DESIGN: Controlled laboratory study. METHODS: Thirty
      subjects, grouped as healthy or with mild shoulder dysfunction, were evaluated
      performing standard push-up plus exercises and modifications on elbows, knees,
      and against a wall. Surface electromyography of the serratus anterior and upper
      trapezius was compared between exercises. RESULTS: Both groups responded
      similarly across exercises. The standard push-up plus demonstrated the highest
      activation of the serratus (to 123%) and lowest trapezius/serratus ratios (<0.2)
      during plus phases. The wall push-up plus and phases of other exercises
      demonstrated higher upper trapezius/serratus ratios (to 2.0). CONCLUSIONS: In
      clinical cases where excess upper trapezius activation or imbalance of serratus
      and trapezius activation occurs, the push-up plus is an optimal exercise. Other
      cases may benefit from a progression of modified push-up exercises. CLINICAL
      RELEVANCE: Clinical selection of exercises for improving scapular control should
      consider both maximum serratus activation and upper trapezius/serratus anterior
      ratios.

PMID- 14977679
TI  - Low back pain in professional golfers: the role of associated hip and low back
      range-of-motion deficits.
AB  - BACKGROUND: Low back pain is fairly prevalent among golfers; however, its precise
      biomechanical mechanism is often debated. HYPOTHESIS: There is a positive
      correlation between decreased lead hip rotation and lumbar range of motion with a
      prior history of low back pain in professional golfers. STUDY DESIGN: A cross
      sectional study. METHODS: Forty-two consecutive professional male golfers were
      categorized as group 1 (history of low back pain greater than 2 weeks affecting
      quality of play within past 1 year) and group 2 (no previous such history). All
      underwent measurements of hip and lumbar range of motion, FABERE's distance, and
      finger-to-floor distance. Differences in measurements were analyzed using the
      Wilcoxon signed rank test. RESULTS: 33% of golfers had previously experienced low
      back pain. A statistically significant correlation (P <.05) was observed between
      a history of low back pain with decreased lead hip internal rotation, FABERE's
      distance, and lumbar extension. No statistically significant difference was noted
      in nonlead hip range of motion or finger-to-floor distance with history of low
      back pain. CONCLUSIONS: Range-of-motion deficits in the lead hip rotation and
      lumbar spine extension correlated with a history of low back pain in golfers.

PMID- 14977680
TI  - Cartilage lesions of the patella in recurrent patellar dislocation.
AB  - BACKGROUND: The etiology of patellar cartilage lesions in recurrent patellar
      dislocation has been poorly understood. HYPOTHESIS: The pathology of cartilage
      lesions of the patella accompanied by recurrent patellar dislocation can be
      analyzed. STUDY DESIGN: Series of case reports. METHODS: In 70 knees from 57
      patients with recurrent patellar dislocation, the cartilage lesions of the
      patella were examined using arthroscopy and/or macroscopic observation. The
      average age of the patients was 22 years (range, 13 to 40 years). Lesions that
      involved only softening were not included. RESULTS: Sixty-seven knees (96%) had
      articular cartilage lesions of the patella, and only 3 knees had no change.
      Fissuring was observed in 53 knees (76%). The most common site of fissuring was
      on the central dome. There were basically two types of fissuring: multiple
      longitudinal fissuring and marginal/radial fissuring. Fibrillation and/or erosion
      were observed in 54 knees (77%). Of these, 40 knees had fissuring and 14 did not
      have fissuring. The main site of fibrillation and/or erosion was the medial
      facet. CONCLUSIONS: Cartilage lesions of the patella in recurrent patellar
      dislocation cases were very common. Fissuring was observed mainly on the central
      dome, and fibrillation and/or erosion were observed mainly on the medial facet.

PMID- 14977681
TI  - Myofibers express IL-6 after eccentric exercise.
AB  - BACKGROUND: Interleukin (IL)-6 is locally produced in skeletal muscles and shows
      a remarkable increase in plasma after eccentric exercises. OBJECTIVE: To
      elucidate the cell types in the muscles responsible for IL-6 production after
      eccentric exercises. STUDY DESIGN: Controlled laboratory study. METHODS: An
      eccentric contraction model was made using electrical stimulation. The authors
      investigated the muscle damage and regeneration processes after eccentric
      exercises histologically, and the cell types expressing IL-6 and its subcellular
      compartimentalization with time immunohistochemically after eccentric exercises.
      RESULTS: Swollen myofibers were detected from 8 hours to 3 days after exercises.
      Disrupted myofibers were detected from 24 hours to 7 days, with a peak of 3 days.
      IL-6 was detected only in the cytoplasm of myofibers until 12 hours; thereafter,
      it was found in the inflammatory cells and proliferating satellite cells as well.
      The swollen myofibers were negatively stained for IL-6. The positive ratios of IL
      6 in myofibers immediately increased after exercises, peaked in 12 hours, and
      then decreased. CONCLUSIONS: After eccentric exercises, IL-6 expression increased
      in myofibers preceding the disruption of myofibers. IL-6 might be closely related
      to muscle damage caused by strenuous exercises.

PMID- 14977682
TI  - Glenohumeral chondrolysis after shoulder arthroscopy: case reports and review of
      the literature.

PMID- 14977683
TI  - Central cord syndrome in a football player with congenital spinal stenosis: a
      case report.

PMID- 14977684
TI  - Kidney trauma in martial arts: a case report of kidney contusion in jujitsu.

PMID- 14977685
TI  - Fatal pulmonary embolism after knee arthroscopy.

PMID- 14977686
TI  - Deep vein thrombosis of the subclavian vein in a college volleyball player.

PMID- 14977687
TI  - Current concepts in anabolic-androgenic steroids.
AB  - Anabolic-androgenic steroids (AAS) are synthetic derivatives of testosterone.
      According to surveys and media reports, the legal and illegal use of these drugs
      is gaining popularity. Testosterone restores sex drive and boosts muscle mass,
      making it central to 2 of society's rising preoccupations: perfecting the male
      body and sustaining the male libido. The anabolic effects of AAS have been
      questioned for decades, but recent scientific investigation of supraphysiologic
      doses supports the efficacy of these regimens. Testosterone has potent anabolic
      effects on the musculoskeletal system, including an increase in lean body mass, a
      dose-related hypertrophy of muscle fibers, and an increase in muscle strength.
      For athletes requiring speed and strength and men desiring a cosmetic muscle
      makeover, illegal steroids are a powerful lure, despite the risk of subjective
      side effects. Recent clinical studies have discovered novel therapeutic uses for
      physiologic doses of AAS, without any significant adverse effects in the short
      term. In the wake of important scientific advances during the past decade, the
      positive and negative effects of AAS warrant reevaluation. Guidelines for the
      clinical evaluation of AAS users will be presented for sports medicine
      practitioners.

PMID- 14977688
TI  - Tunnel enlargement after anterior cruciate ligament surgery.
AB  - Bone tunnel enlargement has been reported after anterior cruciate ligament (ACL)
      reconstruction surgery. Although the long-term outcome of this phenomenon is not
      yet known, tunnel lysis or expansion may be clinically significant in revision
      surgery because the enlarged tunnels may complicate graft placement and fixation.
      There any many proposed theories for tunnel lysis. The most accurate statement is
      that this condition has a multifactorial etiology. Mechanical and biological
      causes have been reported, and both contribute to enlarged graft tunnels. This
      article describes the multiple causes of bone tunnel enlargement after ACL
      surgery. Future techniques and advances in primary ACL surgery must seek to
      eliminate this phenomenon.

PMID- 14977689
TI  - Health, lifestyle, and quality of life for young adults born very preterm.
AB  - BACKGROUND: Children born very preterm and able to attend mainstream schools have
      been shown to have a high prevalence of behavioural, minor motor, and learning
      difficulties. It is not clear whether these problems persist into adulthood,
      impacting on lifestyle and quality of life. METHODS: A previously studied cohort
      of very low birth weight infants born between 1980 and 1983, together with term
      classmate controls, were assessed at age 19-22 years using a postal
      questionnaire. The questionnaire included the SF-36 to assess quality of life, a
      social activities scale, a lifestyle questionnaire, the Hospital Anxiety and
      Depression Scale, and questions on current height, weight, health, family
      structure, and education and occupation. RESULTS: Of the 138 preterm and 163 term
      controls in the cohort, 79 preterm and 71 term returned questionnaires. Quality
      of life was assessed as similar on six of eight domains of the SF-36. Social
      activities were also similar. Preterms drank less alcohol, used fewer illicit
      drugs, but smoked as often. Rates for sexual intercourse were similar, although
      preterms had more children. Preterms were shorter than controls and were less
      satisfied with their appearance. They were more likely to use a regular
      prescription medicine. Fewer were or had been in higher education, and some
      remained unemployed. CONCLUSION: The problems experienced by very preterm infants
      at school appear to influence lifestyle and health, but not perceived quality of
      life in early adulthood.

PMID- 14977690
TI  - The neurodevelopmental progress of infants less than 33 weeks into adolescence.
AB  - BACKGROUND: Several studies have shown an increased incidence of
      neurodevelopmental impairment in very preterm survivors at school age compared
      with controls. AIM: To compare findings in the same cohort at 8 years and 15
      years. METHODS: A total of 151 of the 224 eligible infants born before 33 weeks
      of gestation from 1979 to 1982, and who were living in the UK, were assessed at 8
      and 15 years. Items common to both assessments were compared to evaluate changes
      in neurodevelopmental function. The assessment included a structured neurological
      examination, psychometric tests using the WISC-R (in subjects born in 1981-82), a
      test of visuomotor integration (Beery), and a school questionnaire. RESULTS:
      There was a significant increase in the proportion of subjects classified as
      impaired with disability from 11% at 8 to 22% at 14-15 years of age. The
      proportion of subjects classified as impaired without disability increased from
      16% at 8 to 26% at 14-15 years of age. Full scale IQ decreased from 104 to 95
      from childhood to adolescence, and more adolescents (24%) were requiring extra
      educational provision than they had at the age of 8 years (15%). CONCLUSION:
      Results indicate that between the ages of 8 and 15 years in this cohort of very
      preterm survivors there is an apparent deterioration in neurodevelopmental
      outcome category, cognitive function, and extra educational support. It is not
      clear whether this represents a genuine deterioration in neurocognitive function
      or whether it represents the expression of pre-existing cerebral pathology in an
      increasingly complex environment.

PMID- 14977692
TI  - Randomised controlled trial of swaddling versus massage in the management of
      excessive crying in infants with cerebral injuries.
AB  - BACKGROUND: Infants with neonatal cerebral insults are susceptible to excessive
      crying as a result of difficulties with self-regulation. AIMS: To compare the
      effectiveness of swaddling versus massage therapy in the management of excessive
      crying of infants with cerebral insults. METHODS: Randomised three-week parallel
      comparison of the efficacy of two intervention methods. Infants with symptoms of
      troublesome crying and their parents were randomly assigned to a swaddling
      intervention group (n = 13) or a massage intervention group (n = 12). RESULTS:
      The amount of total daily crying decreased significantly in the swaddling group,
      but did not decrease significantly in the massage group. Infant behavioural
      profiles and maternal anxiety levels improved significantly in the swaddling
      group post-intervention. Parents in the swaddling group were more satisfied with
      the effectiveness of the intervention in reducing crying than parents in the
      massage group. CONCLUSION: Results indicate that swaddling may be more effective
      than massage intervention in reducing crying in infants with cerebral injuries.

PMID- 14977693
TI  - Relation of arterial stiffness with gestational age and birth weight.
AB  - BACKGROUND: The cardiovascular risk of individuals who are born small as a result
      of prematurity remains controversial. Given the previous findings of stiffer
      peripheral conduit arteries in growth restricted donor twins in twin-twin
      transfusion syndrome regardless of gestational age, we hypothesised that among
      children born preterm, only those with intrauterine growth retardation are
      predisposed to an increase in cardiovascular risks. AIM: To compare brachioradial
      arterial stiffness and systemic blood pressure (BP) among children born preterm
      and small for gestational age (group 1, n = 15), those born preterm but having
      birth weight appropriate for gestational age (group 2, n = 36), and those born at
      term with birth weight appropriate for gestational age (group 3, n = 35).
      METHODS: Systemic BP was measured by an automated device (Dinamap), while
      stiffness of the brachioradial arterial segment was assessed by measuring pulse
      wave velocity (PWV). The birth weight was adjusted for gestational age and
      expressed as a z score for analysis. RESULTS: The 86 children were studied at a
      mean (SD) age of 8.2 (1.7) years. Subjects from group 1, who were born at 32.3
      (2.0) weeks' gestation had a significantly lower z score of birth weight (-2.29
      (0.63), p<0.001), compared with those from groups 2 and 3. They had a
      significantly higher mean blood pressure (p<0.001) and their diastolic blood
      pressure also tended to be higher (p = 0.07). Likewise, their brachioradial PWV,
      and hence arterial stiffness, was the highest of the three groups (p<0.001).
      While subjects from group 2 were similarly born preterm, their PWV was not
      significantly different from that of group 3 subjects (p = 1.00) and likewise
      their z score of birth weight did not differ (-0.01 (0.71) v -0.04 (1.1), p =
      1.00). Brachioradial PWV correlated significantly with systolic (r = 0.31, p =
      0.004), diastolic (r = 0.38, p<0.001), and mean (0.47, p<0.001) BP, and with z
      score of birth weight (r = -0.43, p<0.001). Multiple linear regression identified
      mean BP and z score of birth weight as significant determinants of PWV.
      CONCLUSION: The findings of the present study support the hypothesis that among
      children born preterm, only those with intrauterine growth retardation are
      disadvantaged as a result of increase in systemic arterial stiffness and mean
      blood pressure.

PMID- 14977695
TI  - Capture-recapture to estimate the number of street children in a city in Brazil.
AB  - BACKGROUND: Street children are an increasing problem in Latin America. It is
      however difficult to estimate the number of children in the street as this is a
      highly mobile population. AIMS: To estimate the number of street children in
      Aracaju, northeast Brazil, and describe the characteristics of this population.
      METHODS: Three independent lists of street children were constructed from a non
      governmental organisation and cross-sectional surveys. The number of street
      children was estimated using the capture-recapture method. The characteristics of
      the children were recorded during the surveys. RESULTS: The estimated number of
      street children was 1456. The estimated number of street children before these
      surveys was 526, although non-official estimates suggested that there was a much
      larger population. Most street children are male, maintain contact with their
      families, and are attending school. Children contribute to the family budget a
      weekly average of R21.2 dollars (4.25 pounds sterling, 6.0 euros, US7.5 dollars)
      for boys and R17.7 dollars(3.55 pounds sterling, 5.0 euros, US6.3 dollars) for
      girls. CONCLUSION: Street children of Aracaju have similar characteristics to
      street children from other cities in Brazil. The capture-recapture method could
      be a useful method to estimate the size of this highly mobile population. The
      major advantage of the method is its reproducibility, which makes it more
      acceptable than estimates from interested parties.

PMID- 14977696
TI  - Gratification disorder ("infantile masturbation"): a review.
AB  - BACKGROUND: Little has been published on gratification disorder ("infantile
      masturbation") in early childhood. AIMS: To expand on the profile of patients
      diagnosed with this condition. METHODS: Retrospective case note review; Fraser of
      Allander Neurosciences Unit paediatric neurology outpatient department 1972-2002.
      RESULTS: Thirty one patients were diagnosed (11 males and 20 females). Twenty one
      were referred for evaluation of possible epileptic seizures or epilepsy. The
      median age at first symptoms was 10.5 months (range 3 months to 5 years 5
      months). The median age at diagnosis was 24.5 months (range 5 months to 8 years).
      The median frequency of events was seven times per week, and the median length
      2.5 minutes. Events occurred in any situation in 10 children, and in a car seat
      in 11. Types of behaviour manifested were dystonic posturing in 19, grunting in
      10, rocking in 9, eidetic imagery in 7, and sweating in 6. Two children had been
      previously diagnosed as having definite epilepsy. In nine cases home video was
      invaluable in allowing confident diagnosis. CONCLUSION: Gratification disorder,
      otherwise called infantile masturbation, is an important consideration in the
      differential diagnosis of epilepsy and other paroxysmal events in early
      childhood. Home video recording of events often prevents unnecessary
      investigations and treatments.

PMID- 14977697
TI  - Intestinal permeability is increased in bronchial asthma.
AB  - BACKGROUND: Increased intestinal permeability has been reported in one study of
      adult asthmatics. AIM: To determine whether children with asthma have altered
      intestinal permeability. METHODS: Thirty two asthmatic children, and 32 sex and
      age matched controls were recruited. The dual sugar (lactulose and mannitol) test
      was used to evaluate intestinal permeability, and the percentage of ingested
      lactulose (L) and mannitol (M) in the urine, and the L:M ratio were determined.
      All patients were skin prick tested for common aeroallergens, and specific IgE to
      some food items was determined. RESULTS: The median value of L in asthmatic
      children (2.29, IQR 0.91-4.07) was significantly higher than that in controls
      (0.69, IQR 0.45-1.08), and that of M was almost similar. The ratio L:M was
      significantly higher in asthmatic children (0.20, IQR 0.11-0.40) than in controls
      (0.06, IQR 0.04-0.09). Intestinal permeability did not correlate with eczema,
      inhaled steroids, positive skin prick test to aeroallergens, or severity of
      asthma. CONCLUSIONS: Intestinal permeability is increased in children with
      asthma, suggesting that the whole mucosal system may be affected.

PMID- 14977698
TI  - Alpha1 antitrypsin and the prevalence and severity of asthma.
AB  - In a random sample of children (aged 9-11 years; n = 5629), who were studied
      according to the ISAAC phase II protocol, heterozygosity of the alpha1
      antitrypsin (alpha1-AT) Pi genotypes MS or MZ, or low alpha1-AT plasma levels,
      were not associated with an increased risk of developing asthma. Asthmatics with
      low levels of alpha1-AT were particularly prone to develop airway
      hyperresponsiveness and reduced lung function.

PMID- 14977699
TI  - Hospital accessibility and infant death risk.
AB  - This study of all 4889 infant deaths within the cohort of all 287 993 births in
      Cumbria, northwest England (1950-93), found no evidence of an increased risk of
      infant death with greater travel time to hospitals.

PMID- 14977700
TI  - Rising obesity and expanding waistlines in schoolchildren: a cohort study.
AB  - A cohort of schoolchildren was followed up over 6 years from 1996 to 2001. In the
      final year, 315 of 500 targeted children were measured. Body mass index (BMI)
      increased substantially over time (p<0.001), indicating a further rise in obesity
      into the secondary school years. Two new indicators of obesity were also
      measured. Waist circumference scores rose as substantially as BMI (p<0.001), and
      may be of particular significance given the association between abdominal girth
      in adults and cardiovascular morbidity. International Obesity Task Force measures
      were found to be more stringent than previous criteria, with no significant
      change noted over the time period.

PMID- 14977702
TI  - How a non-allergist survives an allergy clinic.
AB  - This article is the result of six years of sudden, traumatic immersion therapy in
      the world of food allergy, following an innocent remark in 1996 from my then
      clinical director at Queen Mary's Children's Hospital, St Helier (Wrythe Lane,
      Surrey SM5 1AA), saying: "We really do not have much allergy service for children
      in this hospital. Why don't you start an allergy clinic?", and me, as a naive
      relatively new consultant, agreeing. This has been added to by also doing the
      Paediatric Allergy Clinic at the Royal Brompton Hospital, with Professor Stephen
      Durham.

PMID- 14977703
TI  - Environmental toxins; their impact on children's health.
AB  - Contamination of the environment by man-made and natural toxins has a direct
      impact on the health of children. This review considers how toxic contamination
      is identified and regulated, and highlights specific hazards.

PMID- 14977704
TI  - Sending children home on tracheostomy dependent ventilation: pitfalls and
      outcomes.
AB  - In spite of the consistency of the primary discharge coordinator in our practice
      and attempts to streamline the process, the obstacles to discharge highlighted
      five years ago remain frustratingly similar. The children in this survey spent an
      average of 9.6 months extra time in hospital awaiting discharge at considerable
      cost to the local commissioning teams, quite apart from the emotional cost to the
      child and stress for the whole family. We hope in future years this review will
      enable health practitioners and local health providers to anticipate the hurdles,
      address the problems early, and expedite the process of discharging home children
      who are dependent on long term ventilation via tracheostomy.

PMID- 14977705
TI  - Clusters of meningococcal disease in school and preschool settings in England and
      Wales: what is the risk?
AB  - AIMS: To assess the risk of further cases in educational settings in order to
      inform policy on managing cases and clusters of meningococcal disease. METHODS:
      Between 1 April 1995 and 31 March 2001, surveillance in preschool and school
      settings in England and Wales identified 114 clusters of meningococcal disease.
      Twenty clusters were reported in preschool settings, 43 in primary, 46 in
      secondary, and five in independent schools. Seventy three clusters (64%)
      consisted of two or more confirmed cases, of which 30 had two or more serogroup C
      cases. Following the introduction of the national meningococcal serogroup C
      vaccination programme in 1999, no serogroup C clusters were observed between
      April 2000 and March 2001. RESULTS: The relative risk of further cases in the
      four weeks after a single case compared with the background rate was raised in
      all settings, ranging from RR 27.6 (95% CI 15.2 to 39.9) in preschool settings to
      RR 3.6 (95% CI 2.5 to 4.6) in secondary schools. Absolute risk estimates ranged
      from 70/100 000 in preschool settings to 3.0/100 000 in secondary schools. The
      relative risk of clustering was similar for serogroup B and C strains. Most (68%)
      second cases occurred within seven days of the first case. CONCLUSIONS: Although
      there was a higher risk of further cases of meningococcal disease in schools and
      especially in preschool settings, it is not known whether widespread antibiotic
      use after single cases reduces risk of further cases and if there is a real risk
      of harm. Evidence of risk reduction is needed to inform public health policy.

PMID- 14977706
TI  - Delayed chemoreceptor responses in infants with apnoea.
AB  - AIMS: To test the hypothesis that apnoea of infancy (AOI) is due to a deficit in
      chemoreception. METHODS: Tests were performed on 112 infants: 43 healthy control
      infants, 28 infants with periodic breathing or central apnoea (PBCA), and 41
      infants with obstructive apnoea (OA) on overnight polysomnography. Chemoreceptor
      responses to hypercapnia (4% and 6% CO2 in air) for 6-8 minutes and hyperoxia
      (100% O2) for 60 seconds were expressed in terms of response strength and
      reaction time. Age at birth (gestational week 37-41) and age at test (2-34
      postnatal weeks) were comparable across groups (median, min-max value). A total
      of 70 CO2 and 71 O2 tests were analysed. RESULTS: The strongest and fastest CO2
      responders were control infants: their median increase in ventilation was
      291%/kPaCO2 and their reaction time 16 breaths. In infants with PBCA and OA, the
      increase in ventilation was 41% and 130%/kPaCO2, and reaction time 64 and 54
      breaths, respectively. There was a significant negative correlation between CO2
      response strength and response time. In response to hyperoxia there was a
      comparable decrease in ventilation in all infants (12-20%), but a significantly
      longer response time in infants with apnoea (20 v 12 breaths). There was no
      correlation between the response strength and response time to O2 and CO2.
      CONCLUSION: An inappropriate central control of respiration is an important
      mechanism in the pathogenesis of apnoea of infancy.

PMID- 14977707
TI  - A multivariate "time based" analysis of SIDS risk factors.
AB  - AIMS: To investigate the influence of analytical design on the variability of
      published results in studies of sudden infant death syndrome (SIDS). METHODS: The
      results of a prospective case-control study, of 203 cases of SIDS, and 622
      control infants are presented. All variables significant on univariate analysis
      were included in a multivariate model analysed in nine stages, starting with
      sociodemographic variables, then sequentially and cumulatively adding variables
      relating to pregnancy history, current pregnancy, birth, the interval from birth
      to the week prior to death, the last week, the last 48 hours, and the last sleep
      period. A ninth stage was created by adding placed to sleep prone for the last
      sleep period. RESULTS: As additional variables are added, previously published
      SIDS risk factors emerged such as social deprivation, young maternal age, > or =3
      previous live births, maternal smoking and drinking, urinary tract infection in
      pregnancy, reduced birth weight, and the infant having an illness, regurgitation,
      being sweaty, or a history of crying/colic in the interval from birth to the week
      before death, with co-sleeping and the lack of regular soother use important in
      the last sleep period. As the model progressed through stages 1-9, many
      significant variables became non-significant (social deprivation, young maternal
      age, maternal smoking and drinking) and in stage 9 the addition of placed to
      sleep prone for the last sleep period caused > or =3 previous live births and a
      reduced birth weight to become significant. CONCLUSION: The variables found to be
      significant in a case-control study, depend on what is included in a multivariate
      model.

PMID- 14977708
TI  - Sickle cell disease pain in London and the Caribbean.

PMID- 14977709
TI  - Wheezing with a whistle.

PMID- 14977710
TI  - Parents measuring pulses; an observational study.
AB  - Parent reported pulse rates could provide important information on a child's
      clinical condition. The agreement between the parent's measurement of their
      child's pulse and a pulse oximeter was assessed following a brief educational
      intervention. Parents can be taught to measure the pulse of school age children,
      but have difficulty with preschool children.

PMID- 14977711
TI  - Ibuprofen and acute renal failure in a toddler.

PMID- 14977712
TI  - When is an abnormal frenulum a sign of child abuse?

PMID- 14977713
TI  - Evidence based guideline for post-seizure management in children presenting
      acutely to secondary care.
AB  - This evidence based guideline covers the immediate management of a child
      presenting to hospital with a febrile or afebrile seizure, once the fit has
      stopped.

PMID- 14977714
TI  - My life with Asperger's syndrome.

PMID- 14977715
TI  - Continuing decline in acute asthma episodes in the community.
AB  - BACKGROUND: Acute asthma episodes prompting consultation with general
      practitioners in the sentinel practices of the Weekly Returns Service (WRS) of
      the Royal College of General Practitioners increased through the 1980s and early
      1990s, reaching a peak in 1993. AIMS AND METHODS: To report on trends in the
      incidence of asthma episodes in children reported to the WRS over the period 1980
      2002. RESULTS: Data confirm the steady upward trend from 1980 to 1993. The
      downward trend since 1993 was consistent in both male and female preschool and
      school age children, in all regions of the country simultaneously, and during all
      seasons until 1999 since when it has stabilised. No causative factor has been
      identified and no temporal association found between factors previously
      postulated as causing the increase in acute asthma. The decline in acute asthma
      episodes in children is consistent with observed declines in all other
      respiratory infections in this community.

PMID- 14977716
TI  - Beyond the evidence.

PMID- 14977717
TI  - Towards evidence based medicine for paediatricians.

PMID- 14977718
TI  - Should we screen every child with otitis media with effusion for allergic
      rhinitis?

PMID- 14977719
TI  - Should we treat infantile seborrhoeic dermatitis with topical antifungals or
      topical steroids?

PMID- 14977720
TI  - Is routine EEG helpful in the management of complex febrile seizures?

PMID- 14977722
TI  - Vitamin B-12 in Crohn's disease patients with small bowel surgery.

PMID- 14977723
TI  - Chronic urticaria and coeliac disease.

PMID- 14977724
TI  - Experimental evidence that ovary and oviducal gland extracts influence male
      agonistic behavior in squids.
AB  - Recent investigations of sensory and behavioral cues that initiate sexual
      selection processes in the squid Loligo pealeii have determined that egg capsules
      deposited on the substrate provide a strong visual and chemotactile stimulus to
      males, even in the absence of females (1, 2, 3). The visual stimulus of egg
      capsules attracts males to the eggs, and when the males touch the eggs, they
      encounter a chemical stimulus that leads to highly aggressive fighting behavior.
      We have recently demonstrated that egg capsule extracts implanted in artificial
      egg capsules elicit this aggressive behavior (4). In this communication, we
      present evidence that the salient chemical factor originates in the ovary and
      perhaps the oviducal gland of the female reproductive tract.

PMID- 14977725
TI  - Contraction and stiffness changes in collagenous arm ligaments of the stalked
      crinoid Metacrinus rotundus (Echinodermata).
AB  - Shortening and stiffness were measured simultaneously in the aboral ligament of
      arms of sea lilies. Arm pieces were used from which oral tissues (including
      muscles) were removed, leaving only collagenous ligaments connecting arm
      ossicles. Chemical stimulation by means of artificial seawater with an elevated
      concentration of potassium caused both a bending movement and stiffness changes
      (either softening or stiffening). The movement lasted for 1.5-10 min, and bent
      posture was maintained. The observation that contraction was not necessarily
      associated with softening provided evidence against the hypothesis that the
      shortening of the aboral ligaments was driven by the elastic components that had
      been charged by the oral muscles and released their strain energy at the
      softening of the aboral ligaments. The speed of ligamental shortening was slower
      by at least one order of magnitude than that of muscles. Acetylcholine (10(-5)
      10(-3) M) caused both contraction and softening. We conclude that the aboral
      ligament shows two mechanical activities based on different mechanisms: one is
      active contraction and the other is connective tissue catch in which passive
      mechanical properties show mutability. We suggest that there is neural
      coordination between the two mechanisms.

PMID- 14977726
TI  - Identification of juvenile hormone-active alkylphenols in the lobster Homarus
      americanus and in marine sediments.
AB  - We have identified, by gas chromatography/mass spectrometry, four alkylphenols
      that are present in the hemolymph and tissues of the American lobster Homarus
      americanus and in marine sediments. These alkylphenols are used industrially in
      antioxidant formulations for plastic and rubber polymer manufacturing, and are
      similar in structure to a known endocrine disruptor, bisphenol A. The compound 2
      t-butyl-4-(dimethylbenzyl)phenol was present at concentrations of 0.02 to 1.15
      microg/ml in hemolymph and 8.95 to 21.58 microg/g in sediments. A second
      compound, 2,4-bis-(dimethylbenzyl)phenol, was present at concentrations between
      0.07 and 19.78 microg/ml in hemolymph and 138.94 to 224.89 microg/g in sediment,
      while a third compound, 2,6-bis-(t-butyl)-4-(dimethylbenzyl)phenol, was found at
      concentrations between 0.01 and 13.00 microg/ml in hemolymph, 2.55 and 6.11
      microg/g in hepatopancreas, and 47.85 and 74.66 microg/g in sediment. A fourth
      compound, 2,4-bis-(dimethylbenzyl)-6-t-butylphenol, was found at concentrations
      of 0.20 to 70.71 microg/ml in hemolymph, 23.56 to 26.89 microg/g in
      hepatopancreas, and 90.68 to 125.58 microg/g in sediment. These compounds, along
      with bisphenol A, 4-dimethylbenzylphenol, and nonylphenol, display high juvenile
      hormone activity in bioassays. Alkylphenols at high concentrations are toxic to
      crustaceans and may contribute significantly to lobster mortality; at lower
      concentrations, they are likely to have endocrine-disrupting effects.

PMID- 14977727
TI  - Reproduction and development of the conspicuously dimorphic brittle star
      Ophiodaphne formata (Ophiuroidea).
AB  - Ophiodaphne formata is a conspicuously dimorphic ophiuroid; the disk diameters
      are approximately 1 mm for males and 5 mm for females. The dwarf male clings to
      the larger female, with the oral surfaces and bursae of the paired ophiuroids
      closely appressed. Moreover, the female of each pair adheres aborally to the oral
      surface of a host sand dollar, Astriclypeus manni. Spawning and external
      fertilization occur in August, at Tsuruga Bay, Sea of Japan. Development of the
      dimorphic brittle star O. formata is described for the first time, from spawning
      through metamorphosis, with special attention to the formation of the skeletal
      system and the external morphology of early juveniles. Fertilized eggs are about
      90 microm in diameter, pale pink, and negatively buoyant. The embryos undergo
      equal, total, and radial cleavage, and the larval skeleton first forms as a pair
      of tetraradiate spicules. Larval development proceeds to an 8-armed
      planktotrophic ophiopluteus, with skeletal elements that consist of a body rod
      and two recurrent rods. Three weeks after fertilization, all the pluteal arms,
      except for the postero-lateral arms, are absorbed, and the metamorphosing larvae
      sink to the bottom. Metamorphosis is completed 21.5 days after fertilization, and
      the resulting juvenile is pentagonal and approximately 270 microm in diameter.
      The smallest specimen (480 microm in disk diameter) collected by field sampling
      exhibited male features on the skeletal plates of the jaw and disk. Sexual
      dimorphism, the peculiar pairing behavior, and the close relationship with the
      host sand dollar may have evolved as distinct reproductive characteristics in
      this ophiuroid with its typical ophiopluteus larvae.

PMID- 14977728
TI  - Waveform dynamics of spermatozeugmata during the transfer from paternal to
      maternal individuals of Membranipora membranacea.
AB  - Analysis of standard (60 frames/s) and high-speed (200 frames/s) video records
      revealed that unencapsulated sperm aggregates (spermatozeugmata) of the
      gymnolaemate bryozoan Membranipora membranacea spontaneously generate at least
      three types of waveforms: small amplitude, large amplitude, and reverse. All
      three waveforms significantly differed from one another in amplitude.
      Additionally, small- and large-amplitude waveforms propagated from the base to
      the tip of axonemes, whereas the reverse waveform propagated from the tip to the
      base of axonemes. Small-amplitude waveforms, which were generated most frequently
      by spermatozeugmata in the paternal perivisceral coelom and in the water column
      after spawning, produced almost no curvature of the axoneme. Large-amplitude
      waveforms were produced by spermatozeugmata in the water column and within
      lophophores. Reverse waveforms were produced while spermatozeugmata moved tail
      end forward through the paternal tentacles during spawning and after
      spermatozeugmata had contacted the intertentacular organ (ITO), a tubular
      structure that spermatozeugmata pass through to enter the maternal coelom and
      that eggs pass through to enter the seawater. The production of reverse waveforms
      by spermatozeugmata after reaching the ITO may be evidence for a behavioral
      response of bryozoan sperm to conspecific maternal individuals.

PMID- 14977729
TI  - Differences in the rDNA-bearing chromosome divide the Asian-Pacific and Atlantic
      species of Crassostrea (Bivalvia, Mollusca).
AB  - Karyotype and chromosomal location of the major ribosomal RNA genes (rDNA) were
      studied using fluorescence in situ hybridization (FISH) in five species of
      CRASSOSTREA: three Asian-Pacific species (C. gigas, C. plicatula, and C.
      ariakensis) and two Atlantic species (C. virginica and C. rhizophorae). FISH
      probes were made by PCR amplification of the intergenic transcribed spacer
      between the 18S and 5.8S rRNA genes, and labeled with digoxigenin-11-dUTP. All
      five species had a haploid number of 10 chromosomes. The Atlantic species had 1-2
      submetacentric chromosomes, while the three Pacific species had none. FISH with
      metaphase chromosomes detected a single telomeric locus for rDNA in all five
      species without any variation. In all three Pacific species, rDNA was located on
      the long arm of Chromosome 10 (10q)--the smallest chromosome. In the two Atlantic
      species, rDNA was located on the short arm of Chromosome 2 (2p)--the second
      longest chromosome. A review of other studies reveals the same distribution of
      NOR sites (putative rDNA loci) in three other species: on 10q in C. sikamea and
      C. angulata from the Pacific Ocean and on 2p in C. gasar from the western
      Atlantic. All data support the conclusion that differences in size and shape of
      the rDNA-bearing chromosome represent a major divide between Asian-Pacific and
      Atlantic species of CRASSOSTREA: This finding suggests that chromosomal
      divergence can occur under seemingly conserved karyotypes and may play a role in
      reproductive isolation and speciation.

PMID- 14977730
TI  - Occurrence in the field of a long-term, year-round, stable population of
      placozoans.
AB  - Long-term field studies on placozoans (Trichoplax adhaerens), including both
      substrate sampling and slide sampling, were carried out at a subtidal site near
      Shirahama, Japan. Samples of natural substrate materials from the field, such as
      stones, shells, or fragments of coral, were particularly useful for obtaining
      placozoans. Results from the substrate sampling indicate that placozoans are
      present year-round at the study site. Large intermittent peaks in the number of
      animals collected at the study site occurred roughly once a year, between late
      summer and the beginning of winter. Placozoans were present every year from 1989
      through 2000. A seawater aquarium was also studied and provided a considerable
      number of placozoans for more than 1 year.

PMID- 14977731
TI  - Vascular endothelial function related to cardiac surgery.

PMID- 14977732
TI  - Bleeding following coronary surgery after preoperative low-molecular-weight
      heparin.
AB  - Low-molecular-weight heparin and acetyl salicylic acid have become an established
      treatment for unstable angina. A retrospective study on our database of one year
      was carried out to see what impact preoperative low-molecular-weight heparin
      versus none had on the postoperative course of 473 patients having coronary
      surgery exclusively. Apart from the fact that the low-molecular-weight heparin
      patients had a higher New York Heart Association classification and marginally
      more grafts, longer bypass and cross-clamp time, the preoperative characteristics
      and surgery of the two groups were similar. The low-molecular-weight heparin
      group had twice as many (9.7% versus 4.7%) re-operations for bleeding, 46% versus
      26% had blood transfusion and 22.3% versus 12.6% plasma transfusion. The
      postoperative outcome was otherwise similar. Preoperative treatment of unstable
      angina with low-molecular-weight heparin carries a definite risk of postoperative
      bleeding. Although this study did not reveal any serious consequences, bleeding,
      transfusions and re-operations are associated with infections, wound healing
      problems and death. The indications and length of treatment with low-molecular
      weight heparin in unstable angina patients have to be appropriate and the
      perioperative management of these patients has to address the bleeding tendency.

PMID- 14977733
TI  - The use of autologous pericardium for complicated mitral valve annulus.
AB  - The study aims to discuss annular repair using the autologous pericardial patch
      in cases with severe mitral ring calcification and endocarditis during mitral
      valve replacement. In the study, annular reconstruction was applied, during
      mitral valve replacement, to 8 patients who had extensive annular calcification
      or annular destruction due to endocarditis. After annular resection, a two
      centimeter wide autologous pericardial patch was sutured continuously to the left
      ventricular wall close to the posterior annulus. After the valve sutures with
      pledgets were placed at the back of the pericardial patch, the other edge of the
      patch was sutured continuously to the left atrial posterior wall. Suturing was
      complete after the whole annulus was encircled. Thereafter, an appropriately
      sized mechanical prosthesis valve was used. One patient died postoperatively due
      to low cardiac output (early mortality 12.5%). Echocardiographical paravalvular
      leakage was not detected in any of the cases during follow-up. Annular dehiscence
      and other annular pathologies were also not detected. This reconstructive
      approach may positively influence mortality and morbidity in cases with
      complicated mitral pathologies.

PMID- 14977734
TI  - Open fixation in flail chest: review of 64 patients.
AB  - The strategy for treatment of flail chest remains controversial. Various
      alternatives were assessed by reviewing the records of 64 patients treated from
      1991 through 2000. Patients were classified according to therapeutic approach:
      group 1 was 27 patients who underwent open fixation of the fractured ribs, group
      2 was 19 patients managed by intermittent positive-pressure ventilation, and
      group 3 was 18 patients managed mainly by synchronized intermittent mandatory
      ventilation. Two patients initially treated by ventilation underwent successful
      open fixation. In group 1, ventilatory support was required in 21 (77.8%)
      patients postoperatively, the mean duration of ventilation was 3.1 days, mean
      hospital stay was 18.3 days, morbidity was 11.1% (3/27), and mortality was 11.1%.
      In groups 2 and 3, the mean time for stabilization of paradoxical chest wall
      movement was 6.6 days, and mean duration of ventilation was 7.2 days. Mortality
      was 27.0% (10/37) in patients treated nonsurgically; 21.0% (4/19) in group 2, and
      33.3% (6/18) in group 3. In groups 2 and 3, pain control required epidural
      analgesia in 13 (35.1%) cases, intercostal nerve blockade in 16 (43.2%), and
      narcotic or nonnarcotic parenteral analgesia in 8 (21.6%). Open fixation is a
      successful treatment modality for traumatic flail chest.

PMID- 14977735
TI  - Interlocking sternotomy: initial experience.
AB  - An interlocking sternotomy using a lazy-S-shaped incision was performed in 91
      patients undergoing cardiac surgical procedures (group A). The results were
      compared with those of 77 patients (group B) who underwent a standard sternotomy
      by the same surgical team. In group A, the incidence of sternal instability was
      2.27% (2/88) versus 8.21% (6/73). No dehiscence or mediastinitis was noted in
      group A, whereas 6.85% (5/73) in group B had this complication. Analysis of
      diabetics revealed no sternal complication in group A compared to 50% (3/6) in
      group B. The interlocking sternotomy significantly reduced the incidence of
      sternal instability and helped to prevent sternal dehiscence and mediastinitis.
      Use of this safe, simple, and reproducible technique is strongly recommended,
      especially in diabetics.

PMID- 14977736
TI  - Application of mechanical dilatation of the pyloric sphincter in esophagectomy
      for esophageal carcinoma.
AB  - The objective of this study was to investigate the effectiveness of additional
      intraoperative mechanical dilatation of the pyloric sphincter in order to prevent
      early postoperative gastric retention after esophagectomy using the stomach as
      substitute for esophageal carcinoma patients. Between October 2001 and May 2002,
      32 consecutive esophageal carcinoma patients were treated with esophagectomy
      combined with additional intraoperative mechanical dilatation of pyloric
      sphincter (trial group). Another 30 patients underwent esophagectomy without
      additional intraoperative mechanical dilatation of the pyloric sphincter (control
      group). Both groups were compared in the following aspects: amount of
      postoperative GI drainage, time of flatus, intrathoracic gastric fluid retention
      and other surgical related complications. The amount of GI drainage in the trial
      group was significantly less than that in the control group (p < 0.05), and time
      of anal exsufflation was 1 to 2 days. X-ray demonstrated only 0 to 25% of
      intrathoracic gastric fluid retention and no related complications such as
      anastomotic leakage, so the patients in the trial group suffered less gastric
      reflux. Additional intraoperative mechanical dilatation of the pyloric sphincter
      in radical esophagectomy can accelerate gastric emptying, the recovery of gastric
      intestinal function and obviously decrease the occurrence of early postoperative
      gastric retention and related complications. This method does have the advantages
      of ease of performance, confirmed effectiveness and safety. It can be utilized in
      radical esophagectomy through any approach of thoracotomy.

PMID- 14977737
TI  - Simple method for rapid diagnosis of tuberculosis pleuritis: a statistical
      approach.
AB  - Among the extrapulmonary presentations of tuberculosis, pleural tuberculosis is
      the second most frequent. Failure to diagnose and treat pleural tuberculosis can
      result in progressive disease with involvement of other organs in as many as 65%
      of patients. Conventional methods such as direct examination of pleural fluid,
      pleural fluid culture and pleural biopsy have proven to be insufficient for
      diagnoses of pleural tuberculosis. In this study, we examined a statistical
      method by combining the diagnostic efficiency of adenosine deaminase activity,
      pleural fluid protein, lactate dehydrogenase and cellular components in patients
      with tuberculous pleural effusions. Eighty eight patients over 12 years of age
      presenting with pleural effusions were included. A positive result by either
      three of the methods was considered to be indicative of a positive diagnosis of
      pleural tuberculosis. The determination of adenosine deaminase activity, lactate
      dehydrogenase levels, and lymphocyte to neutrophil ratio in the pleural fluid
      yielded a sensitivity of 100% for pleural tuberculosis. A patient was considered
      positive if any of the three tests was positive, with a specificity of 100%. A
      positive diagnosis was made when all three tests were positive. Similarly, these
      different approaches to the combination of pleural adenosine deaminase and
      lactate dehydrogenase result in sensitivity and specificity of 91.4% and 100%
      respectively.

PMID- 14977738
TI  - Multivessel total arterial revascularization via left thoracotomy.
AB  - Off-pump coronary artery bypass grafting is now becoming the preferred method of
      coronary revascularization. The trend is towards complete revascularization,
      preferably arterial. We are describing here a method of multivessel, total
      arterial, complete revascularization via an anterolateral thoracotomy approach in
      27 patients. There was an average of 3.2 grafts/patient. Angiograms were
      performed in 9 patients (33.33 %). There were no operative mortalities. None of
      the patients required conversion to cardiopulmonary bypass or midsternotomy.

PMID- 14977739
TI  - Predicting the response to lung volume reduction surgery using scintigraphy.
AB  - This study was conducted to evaluate the use of quantitative scintigraphy with a
      newly designed marker to assess and predict the efficacy of lung volume reduction
      surgery in treating emphysema. In a series of 50 patients with severe emphysema
      who underwent the operation, ventilation/perfusion scintigraphy was performed and
      2 markers of area ratio and lung uniformity were measured before and 6 months
      after surgery. The markers were correlated with the results of pulmonary function
      tests. The histopathological subtype of emphysema was also determined in the
      resected specimen and related to improvement in the markers. The markers were
      closely related to improvement in forced expiratory volume in 1 second, with the
      highest correlation being the marker lung uniformity measured by perfusion
      scintigraphy. Improvement in this marker was significantly greater in
      centrilobular than in panlobular emphysema. This quantitative method of
      scintigraphy could provide an excellent reflection of surgical efficacy as well
      as predict the surgical outcome. Additionally, it provides a mechanistic
      explanation for the differential improvement between the histopathological
      subtypes of emphysema following surgery.

PMID- 14977740
TI  - Arterial switch operation without coronary translocation: mid-term results.
AB  - We innovated a technique of arterial switch operation without coronary
      translocation in 1995, which avoids problems related to coronary artery
      translocation with good mid-term results. It is a better alternative for surgeons
      who are not well versed with coronary translocation of conventional arterial
      switch operation and with difficult coronary anatomy. This report deals with the
      mid-term results of our new technique.

PMID- 14977741
TI  - Clinical implication of atrial and brain natriuretic Peptide in coronary artery
      bypass grafting.
AB  - Atrial natriuretic peptide and brain natriuretic peptide are known to be indices
      for heart failure. Atrial natriuretic peptide and brain natriuretic peptide
      changes in off-pump and on-pump coronary artery bypass grafting is hypothesized
      to be correlated to clinical implications of coronary artery bypass grafting. 20
      consecutive off-pump and 20 consecutive on-pump coronary artery bypass grafting
      patients were studied. Perioperative atrial natriuretic peptide and brain
      natriuretic peptide values were measured and statistically analyzed in terms of
      14 factors related to myocardial damage and recovery. Postoperative atrial
      natriuretic peptide plateaued on the third postoperative day and it decreased
      gradually down to the preoperative level by one month in the off-pump group.
      Postoperative brain natriuretic peptide plateaued, showed very slow decrease and
      it never reached down to the preoperative level. The peak brain natriuretic
      peptide level was correlated with aortic cross-clamp time, postoperative pleural
      effusion, and postoperative atrial fibrillation (p < 0.01). The atrial
      natriuretic peptide change reflected surgical prevention of ventricular
      remodeling. Brain natriuretic peptide > 450 microg.mL(-1) had strong predictive
      power for atrial fibrillation and pleural effusion and is a useful marker for
      management of coronary surgery patients.

PMID- 14977742
TI  - Activated clotting time during cardiopulmonary bypass: is repetition necessary
      during open heart surgery?
AB  - We evaluated the need of activated clotting time monitoring and efficacy of
      heparinization protocol in 100 patients undergoing open heart surgery. Patients
      were anticoagulated with 300 or 400 units.kg(-1) heparin, based on their heparin
      sensitivity assessed at 5 min by activated clotting time. One-third of the
      initial dose was repeated at 90 min and thereafter hourly until completion of
      cardiopulmonary bypass. Patients who attained an activated clotting time of > 350
      seconds at 5 min were included. Activated clotting time was repeated every 30
      min. A time of < 350 seconds or presence of clot in the surgical
      field/extracorporeal circuit was considered failure of the protocol.
      Cardiopulmonary bypass was performed using a membrane oxygenator, non-pulsatile
      flow, hypothermia and crystalloid/blood priming solution. At 5 min, 94 patients
      had activated clotting time of > 350 seconds, 6 were < 350 seconds. At
      predetermined time intervals of 30 min, up to 210 min, 406 activated clotting
      time measurements were above 400 seconds and 40 were between 350 and 400 seconds.
      No clot was observed in the surgical field or extracorporeal circuit. This
      anticoagulation protocol ensures adequate anticoagulation during hypothermic
      cardiopulmonary bypass. With this protocol, only one activated clotting time at 5
      min after heparin administration is required and essential; subsequent monitoring
      is not necessary.

PMID- 14977743
TI  - Assessment based on EuroSCORE of ministernotomy for aortic valve replacement.
AB  - To assess the advantages of a ministernotomy over a standard sternotomy for
      aortic valve replacement, 191 patients were classified as low-, medium-, and high
      risk by EuroSCORE. A ministernotomy was carried out in 100 patients, and a
      standard sternotomy was used in 91. Among low-risk patients, those who had a
      ministernotomy showed a marginal increase in atrial fibrillation. Of the medium
      risk patients, those who had a sternotomy had significantly more atrial
      fibrillation and slightly more general infections. In the high-risk subgroup,
      significantly more atrial fibrillation was observed in the sternotomy group, and
      more neurologic events were observed in the ministernotomy group; the difference
      became nonsignificant when only severe events were considered. There was a
      significant benefit in terms of rhythm disturbances in medium- and high-risk
      patients who underwent a ministernotomy compared to those who had a full
      sternotomy. Mortality, duration of intensive care, and hospital stay were not
      influenced by the operative method.

PMID- 14977744
TI  - Lung perfusion with oxygenated blood during aortic clamping prevents lung injury.
AB  - To evaluate the protective effect of continuous pulmonary perfusion with
      oxygenated blood during aortic crossclamping, 12 mixed-breed piglets (7-12 kg)
      were placed on cardiopulmonary bypass for 130 minutes. An experiment group of 6
      (group E) had continuous pulmonary perfusion with oxygenated blood during
      cardiopulmonary bypass, while the other 6 served as controls (group C). Pulmonary
      function was measured at the beginning and end of cardiopulmonary bypass and one
      hour later. Histology was compared before and after cardiopulmonary bypass.
      Pulmonary function after cardiopulmonary bypass was significantly better in group
      E than group C. There was preservation of the normal pulmonary parenchyma in
      group E, whereas group C had marked intra-alveolar edema and abundant intra
      alveolar neutrophils. Anoxia of lung tissue during aortic crossclamping on
      cardiopulmonary bypass is probably the major factor in lung injury. Continuous
      pulmonary perfusion was effective in preventing lung injury during aortic
      crossclamping.

PMID- 14977745
TI  - Limiting pericardial adhesions after coronary artery bypass: experimental study.
AB  - Retrosternal pericardial adhesion formation constitutes a major hazard during re
      do coronary artery surgery. To determine whether an onlay parietal pleural flap
      over the internal thoracic artery bed would reduce pericardial adhesions after
      coronary artery grafting, 16 sheep underwent a median sternotomy and both
      internal thoracic arteries were harvested. On the randomly selected study side, a
      dissected pleural flap was used to cover the internal thoracic artery bed, the
      opposite side was left uncovered as a control. Half of the sheep were sacrificed
      at a median of 102 days (range, 93-109 days), the remainder at a median of 176
      days (range, 165-183 days). Two independent observers blinded to the initial
      operation scored the degree of postoperative adhesions. There was a significant
      decrease in adhesion formation on the study side covered by the mobilized pleural
      flap, compared to the control side. There were no increases in pulmonary
      morbidity or sternotomy wound problems from raising the lateral pleural flap.
      This simple technique appears to be an effective method of preventing adhesion
      formation following coronary artery bypass grafting utilizing the internal
      thoracic artery.

PMID- 14977746
TI  - Elective video-assisted thoracoscopic lung biopsy for interstitial lung disease.
AB  - Lung biopsy is often required for the definitive subtype classification of
      interstitial lung disease. The video-assisted thoracoscopic approach has been
      advocated as an alternative to standard open lung biopsy because it is less
      invasive; however, whether it makes a positive contribution to treatment strategy
      remains contentious. We investigated the safety and efficacy of the video
      assisted approach in a retrospective review of 30 consecutive patients who
      underwent the procedure in an elective setting after being diagnosed with
      interstitial lung disease by chest radiography and computed tomography. The mean
      age of the patients was 56.7 years. The preoperative vital capacity and forced
      expiratory volume in 1 second were 80.0% and 83.6%, respectively. There was no
      operative mortality, but 2 cases of respiratory failure and 1 of prolonged air
      leak occurred. The diagnostic yield was 100%, and treatment was changed in 57% of
      the cases as a result of the histological diagnosis. The rate of treatment change
      was higher for patients with nonspecific interstitial pneumonia than for those
      with idiopathic pulmonary fibrosis. We conclude that video-assisted biopsy is
      effective in the subtyping of interstitial lung disease and is a safe procedure
      when performed electively at the early stage of the disease.

PMID- 14977747
TI  - Extensive thoracoabdominal aortic aneurysm repair using deep hypothermic bypass
      and circulatory arrest.
AB  - We sought to evaluate the safety and usefulness of deep hypothermic
      cardiopulmonary bypass with intervals of circulatory arrest for extensive
      thoracoabdominal aortic aneurysms. Between March 1994 and December 2002, 17
      patients with Crawford type I and II were reviewed retrospectively. The patients
      were divided into two groups: group H (hypothermic circulatory arrest, n = 8) and
      group N (normothermic cardiopulmonary bypass, n = 9). In group H, in-hospital
      mortality was 12.5%, and that in group N was 11.1%. Operation times were similar
      between the two groups though the cardiopulmonary bypass time was significantly
      shorter in group N than in group H (p < 0.05). Postoperative paraplegia occurred
      in 1 patient of group N. Postoperative renal dysfunction occurred in none of
      group H except in 1 preoperative dialysis case, whilst it occurred in 6 patients
      of group N. Postoperative creatinine levels were significantly higher in group N
      than in group H. Three cases in group H required tracheostomy. Our experience
      with hypothermic cardiopulmonary bypass and circulatory arrest for diffuse type
      thoracoabdominal aortic aneurysm confirms the safety and efficacy of this
      technique. Although respiratory complications remain a problem, the technique is
      considered to be effective for renal protection.

PMID- 14977748
TI  - Sinus of valsalva aneurysm with congenital aortic stenosis and aortic
      coarctation.
AB  - A 52-year-old female was diagnosed with the extremely rare combination of sinus
      of Valsalva aneurysm, congenital unicuspid aortic valve stenosis, and coarctation
      of the aorta. She was successfully treated in a two-stage operation. The first
      operation consisted of a bypass graft to correct the coarctation. The second,
      performed 31 days later, included aortic valve replacement, patch closure of the
      aneurysm, and translocation of the right coronary artery.

PMID- 14977749
TI  - Bilateral isolated coronary ostial stenosis following mediastinal irradiation.
AB  - Isolated coronary ostial narrowing is rare and may represent a separate disease
      entity from atherosclerotic coronary artery disease. The case of a 41-year-old
      female with no coronary risk factors who developed severe bilateral isolated
      coronary ostial stenosis following mantle radiotherapy for Hodgkin's disease is
      described. She underwent urgent coronary artery bypass grafting and has remained
      well for 3 years.

PMID- 14977750
TI  - Retrograde cerebral perfusion for treatment of air embolism after valve surgery.
AB  - Air embolism occurred after termination of cardiopulmonary bypass in a 22-year
      old man undergoing aortic valve replacement for rheumatic aortic insufficiency.
      Normothermic retrograde cerebral perfusion was instituted for 5 min at a flow
      rate of 300-500 mL.min(-1), maintaining internal jugular vein pressure < 25 mmHg.
      The aortic cannula was declamped intermittently for 5-10 seconds. Mean arterial
      pressure was kept at 60-70 mmHg. The patient recovered without any neurological
      deficit.

PMID- 14977751
TI  - Invasive pulmonary aspergillosis after renal transplantation treated by surgery.
AB  - Invasive pulmonary aspergillosis is a serious complication in immunocompromised
      patients. In those unresponsive to pharmacological treatment, or when drug
      toxicity is excessive, surgery may resolve the condition. A 48-year-old woman
      with invasive pulmonary aspergillosis after renal transplantation underwent
      resection of the right upper lobe and the apical segment of the inferior lobe,
      followed by complete recovery.

PMID- 14977752
TI  - Staphylococcus aureus pancarditis complicated by a left ventricular
      pseudoaneurysm.
AB  - Acute septic pancarditis is a life threatening but fortunately rare condition. We
      report a case of this condition in a young 20-year-old female patient with an
      early complication of mitral valve destruction and a late complication of a left
      ventricular pseudoaneurysm formation.

PMID- 14977753
TI  - Intraoperative view of cardiac lipoma by using a compact camera.

PMID- 14977754
TI  - Ruptured sinus of valsalva aneurysm.

PMID- 14977755
TI  - Coronary artery spasm of a non-culprit vessel during off-pump bypass surgery.

PMID- 14977756
TI  - Risk in elderly patients after stentless versus stented aortic valve surgery.

PMID- 14977758
TI  - Late onset post-keratoplasty astigmatism in patients with keratoconus.

PMID- 14977759
TI  - Willingness to pay for cataract surgery in Kathmandu valley.
AB  - AIM: A cross sectional study was carried out on 78 screened cataract patients of
      two screening camps in Kathmandu valley, Nepal, to assess the willingness to pay
      for cataract surgery. METHODS: A non-probability sampling technique with open
      ended and close ended questionnaires was used. RESULTS: The average age of
      patients was 68.8 years. The ratio of men and women was 0.9:1. 42.3% (33) of
      patients were willing to pay for cataract surgery. Among them 48.5% (16) of
      people were willing to pay less than dollars 13 and 51.5% (17) were willing to
      pay more than dollars 13. The mean was dollars 2.3 (SD dollars 15.5) per case.
      Patients with bilateral cataract were more willing to pay than unilateral cases.
      Poverty (44.4%, 20) was the main barrier for unwillingness to pay for cataract
      surgery. Other reasons were the lack of family support (28.9%, 13), lack of
      knowledge of surgery and belief that it was an unnecessary procedure (15.6%,
      seven), and waiting for a free surgical service (11.1%, five). CONCLUSION: This
      study clearly indicates that although there was awareness of the availability of
      treatment and services provided within the reach, people are not willing to pay
      for the surgery and use the facility primarily because of poverty. Hence, to
      change patients' attitudes, a more holistic approach is needed, keeping in view
      the cultural, social, and economic background of the society.

PMID- 14977760
TI  - Visual outcomes in children in Malawi following retinopathy of severe malaria.
AB  - AIM: To investigate whether retinal changes in children with severe malaria
      affect visual acuity 1 month after systemic recovery. METHODS: All children with
      severe malaria admitted to a research ward in Malawi during one malaria season
      were examined by direct and indirect ophthalmoscopy. Visual acuity was tested in
      those attending follow up by Cardiff cards, Sheridan-Gardiner single letters, or
      Snellen chart. RESULTS: 96 (68%) children attended follow up, of whom 83 (86%)
      had visual acuity measured. Cardiff cards were used in 47 (57%) children, and
      Sheridan-Gardiner letters or Snellen chart in 29 (35%). There was no significant
      difference in the mean logMAR visual acuity between groups with or without
      macular whitening (0.14 versus 0.16, p = 0.55). There was no trend for worse
      visual acuity with increasing severity of macular whitening (p = 0.52) including
      patients in whom the fovea was involved (p = 0.32). Six (4.2%) children had
      cortical blindness after cerebral malaria, and all six had other neurological
      sequelae. Ophthalmoscopy during the acute illness revealed no abnormalities in
      four of these children. CONCLUSION: Retinal changes in severe malaria, in
      particular macular whitening, do not appear to affect visual acuity at 1 month.
      This supports the hypothesis that retinal whitening is due to reversible
      intracellular oedema in response to relative hypoxia, caused by sequestered
      erythrocytes infected by Plasmodium falciparum. Impaired visual functioning after
      cerebral malaria is not attributable to retinal changes and appears to be a
      cortical phenomenon.

PMID- 14977761
TI  - The effects of corneal parameters on the assessment of endothelial cell density
      in the elderly eye.
AB  - BACKGROUND: The possible impact of corneal thickness, curvature, and size on the
      measurement of endothelial cell density (ECD) has largely been ignored in the
      normal eye. The aim of this study was to investigate the possible impact of the
      main corneal parameters on the analysis of ECD values at the central, superior,
      and temporal parts of the corneal surface. METHODS: All 75 participants (52
      females, 23 males) were assessed as part of a pre-cataract surgery investigation.
      The mean age was 75.7 (SD 10.9) years. Confocal microscopy was used to measure
      ECD and the percentage of six sided cells at the central, superior, and temporal
      parts of the cornea. The Orbscan II topography system was used to measure corneal
      thickness, topography, and horizontal corneal diameter. RESULTS: The mean central
      ECD measured was 2488 (SD 301) cells/mm(2), compared with 2525 (SD 505)
      cells/mm(2) in the temporal cornea and 2639 (SD 398) cells/mm(2) in the superior
      cornea. The regional differences in ECD were not significant (p>0.14). The
      central ECD was significantly correlated to the central (mean 0.593 (SD 0.039)
      mm, p = 0.021) as well as the temporal (0.628 (SD 0.039) mm, p<0.001) and the
      superior corneal thickness (SD 0.644 (SD 0.048) mm, p = 0.018). The mean corneal
      curvature at the centre (7.7 (SD 0.34) mm, p = 0.002) as well as 3 and 5 mm from
      the apex was significantly related to ECD (p = 0.008 and p = 0.009,
      respectively). CONCLUSIONS: The study suggests that in an older population, lower
      ECD values would be expected in thinner and/or steeper corneas.

PMID- 14977762
TI  - What patients want to know before they have cataract surgery.
AB  - AIMS: To investigate what patients want to know before undergoing cataract
      surgery. METHODS: A written questionnaire was answered by 190 patients prior to
      cataract surgery. RESULTS: The five pieces of preoperative information rated most
      important were: chance of visual improvement; when vision would improve; overall
      risk of losing vision from the operation; effect of not having the operation, and
      the types of serious complications. When asked "should you be warned of a serious
      complication if it has a risk of happening", 93.5% said yes to a risk of 1 in 50
      and 62.4% to 1 in 1000. Written information was requested by 85.7%. There were
      few differences between the sexes, and between those having their first or second
      operation. CONCLUSIONS: Patients most wanted to know benefits and risks, even
      very small risks. Written information should be provided to ensure coverage and
      reinforce verbal information.

PMID- 14977763
TI  - Patient preferences for anaesthesia management during cataract surgery.
AB  - BACKGROUND/AIMS: To assess patient preferences for different anaesthesia
      management strategies during cataract surgery. METHODS: Cross sectional clinic
      based study of patient preferences for anaesthesia management strategies.
      Patients rated their preferences using a linear rating scale from 0 to 100.
      RESULTS: Subjects tended to prefer block to topical anaesthesia and oral to
      intravenous sedation. On a scale from 0 to 100, subjects preferred oral to
      intravenous sedation and block to topical anaesthesia by about 8 points.
      CONCLUSIONS: When given the choice of four different anaesthesia management
      strategies, 72% of the study subjects preferred block anaesthesia to topical
      anaesthesia. More patients chose to have oral sedation than intravenous sedation.
      These findings indicate that patients may prefer anaesthesia management
      approaches other than the ones they are currently being offered.

PMID- 14977764
TI  - Randomised double masked trial comparing the efficacy and tolerance of 0.05%
      mequitazine eye drops versus 0.05% levocabastine and placebo in allergic
      conjunctivitis induced by a conjunctival provocation test with Dermatophagoides
      pteronyssinus.
AB  - AIM: A double masked randomised trial comparing 0.05% mequitazine eye drops with
      0.05% levocabastine and placebo was carried out in otherwise healthy volunteers
      allergic to house dust mites (Dermatophagoides pteronyssinus). METHOD: Double
      masked, randomised, single centre study, comparing three parallel treatment
      groups. 60 healthy adults with a confirmed history of allergic conjunctivitis to
      house dust mites for at least 2 years were included and completed the trial.
      Conjunctival provocation tests (CPT) were done at screening, at visit 2 (V2) (1
      week later), and at visit 3 (V3) (2 weeks after V2). Treatment was instilled in
      the same eye, 5 minutes after the CPT at V2, and twice daily until V3. CPT were
      scored 5, 10, 15, and 60 minutes after instillation of the dose of
      Dermatophagoides pteronyssinus antigen determined at inclusion (V2, curative
      test) or resulting in positivity (V3, preventive test) RESULTS: In the V2
      (curative) test the difference between the active treatments and placebo on the
      redness+itching scores was not significant. At the V3 (preventive) CPT there was
      a lower number of reactions at the threshold dose with mequitazine (20%) compared
      to placebo (60%, p = 0.01) or levocabastine (45%, p = 0.10). CONCLUSION: This
      trial failed to clearly demonstrate curative superiority of topical
      antihistamines with placebo, when a single dose of treatment was instilled
      following CPT. However mequitazine 0.05% eye drops were superior to placebo in
      preventing a reaction to CPT, after 2 weeks of treatment.

PMID- 14977765
TI  - Long term outcome of secondary glaucoma following vitreoretinal surgery.
AB  - PURPOSE: To determine the long term outcome of secondary glaucoma following
      retinal reattachment surgery. METHOD: A longitudinal retrospective study was
      undertaken of the medical records of patients referred to the Glaucoma Service at
      Moorfields Eye Hospital following retinal reattachment surgery. The main outcome
      measures were final intraocular pressure (IOP), progression in cup:disc ratio,
      and final visual acuity outcome. RESULTS: A total of 70 eyes of 70 patients (41
      males and 29 females) were identified and included in the analysis. Mean increase
      of IOP 2-3 weeks following the first vitreoretinal procedure was 6 (SD 3) mm Hg.
      After a mean follow up of approximately 4 years the mean IOP had significantly
      decreased from 33 (SD 10) to 16 (SD 8) mm Hg (p<0.001). The visual outcome of
      eyes with final IOP less than 6 or greater than 21 mm Hg was significantly worse
      compared with those eyes with a normal (6-21 mm Hg) range of pressure (p = 0.022
      and p = 0.009 respectively). Despite the effective control of IOP in the majority
      of patients during the follow up period, there was mild progression of the mean
      vertical cup:disc ratio from 0.6 (SD 0.2) to 0.7 (SD 0.2) (p<0.001). CONCLUSION:
      Secondary glaucoma is a major complication following retinal reattachment
      surgery. Medical treatment is successful in lowering IOP in most patients. In
      persisting cases surgical treatment is very effective, however it can be
      associated with an increased risk of postoperative hypotony. Despite apparently
      adequate IOP control there may be progressive cupping of the optic disc.

PMID- 14977766
TI  - Intravitreal triamcinolone with photodynamic therapy for subfoveal choroidal
      neovascularisation in age related macular degeneration.
AB  - AIMS: To report the effects of intravitreal triamcinolone acetonide (iTAAC)
      injections as an adjunctive treatment to photodynamic therapy (PDT) with
      verteporfin for new subfoveal choroidal neovascularisation (CNV) in age related
      macular degeneration (AMD). METHODS: We retrospectively reviewed the records of
      all AMD patients who had iTAAC within 6 weeks of their first PDT and had a follow
      up of one year or longer. The proportion of eyes after one year follow up that
      lost or gained >or=15 and >or=30 ETDRS letters, baseline and one year lesion
      greatest linear dimension (GLD), number of PDTs, and side effects were assessed.
      RESULTS: Fourteen patients were evaluated. Eleven received one initial combined
      treatment and three received an additional combined treatment after 6 months.
      Median follow up was 18 months (range 12 to 25 months). Overall, 7% gained >or=30
      letters, 50% maintained stable vision, 14% lost 15-29 letters, and 29% lost
      >or=30 letters. Overall, mean GLD increased from 2580 (SD 1088) microm to 3946
      (SD 1503) micro m (p = 0.01). The mean number of PDTs during the first year was
      2.57. Side effects were mild intraocular pressure elevation in 28.5% and cataract
      progression in 50% of phakic eyes. CONCLUSIONS: iTAAC with PDT in AMD was found
      to be relatively safe and had reasonable results for lesions with some classic
      component.

PMID- 14977767
TI  - Reproducibility of circadian retinal and optic nerve head blood flow measurements
      by Heidelberg retina flowmetry.
AB  - BACKGROUND/AIM: The Heidelberg retina flowmeter (HRF) is designed to measure
      retinal capillary blood flow. Previous studies however showed weak
      reproducibility of data. The intraindividual reproducibility of circadian HRF
      measurements was examined in healthy subjects in three locations of the retina.
      METHODS: 36 healthy volunteers (27.3 (SD 4.3) years) were examined by HRF seven
      times a day (t0-t6). Using a default window of 10 x 10 pixels, three consecutive
      measurements were performed in three precise focusing planes: superficial,
      intermediate and deep layer, peripapillary retina, neuroretinal rim and cup,
      respectively. Images of identical tissue locations identified by capillary
      landmarks of each layer were selected to quantify the retinal microcirculation of
      each volunteer. Means and standard deviations of all flow results of a given
      subject were calculated, at t0-t6 and the coefficients of variation as a measure
      of reproducibility. RESULTS: The coefficients of variation ranged between 8.4%
      and 41.0% in the superficial layer (mean 19.8% (SD 8.4%)), 10.6%, and 43.0% in
      the intermediate layer (mean 24.0% (SD 8.4%)), and 9.9% and 84.0% (mean 29.6% (SD
      15.8%)) in the deep layer. CONCLUSIONS: These data show the best reproducibility
      of measurements in the superficial layer followed by the intermediate and the
      deep layer. Clinically, this is an unsatisfactory intraindividual reproducibility
      of flow values in each studied layer.

PMID- 14977768
TI  - Bloom syndrome: multiple retinopathies in a chromosome breakage disorder.
AB  - AIM: To describe multiple retinal abnormalities in a patient with Bloom syndrome,
      including early macular drusen, diabetic retinopathy, and the onset of leukaemic
      retinopathy. METHODS: Clinical data were collected over 1 year of follow up, and
      ocular abnormalities in Bloom syndrome were reviewed from the literature.
      RESULTS: A 39 year old man with a rare autosomal recessive "chromosome breakage"
      syndrome was followed. A variety of ocular findings have been reported in Bloom
      syndrome; this patient had hard drusen in both maculae, non-proliferative
      diabetic retinopathy, and haemorrhagic retinopathy as a herald of acute
      lymphocytic leukaemia. CONCLUSIONS: Bloom syndrome is a rare disorder of genomic
      instability, in which a variety of ocular abnormalities have been found.
      Described here are multiple retinal manifestations arising from characteristic
      systemic associations of diabetes mellitus and leukaemia, as well as macular hard
      drusen.

PMID- 14977769
TI  - Small margin excision of periocular basal cell carcinoma: 5 year results.
AB  - BACKGROUND: The traditional surgical management of nodular adnexal basal cell
      carcinomas (BCC) involves excision with 3-4 mm margins and primary repair. This
      may remove a significant area of healthy tissue, often necessitating a
      complicated reconstruction, without the confirmation that tumour excision is
      complete. METHODS: Nodular adnexal BCCs were excised with 2 mm margins, and the
      repair delayed for 2 days, providing time for histological confirmation of
      complete excision with formal paraffin sections. Any incompletely excised tumours
      underwent further resection, which was facilitated by the undisturbed wound
      edges. Repair was again delayed until further histological examination had
      confirmed complete excision. RESULTS: 5 year follow up data were available for 55
      patients who had undergone small margin BCC excision with delayed repair. 10
      patients required more than one excision to achieve clear margins. There were no
      recurrences. CONCLUSION: Small margin excision of nodular adnexal BCCs with
      delayed repair is a safe and efficient method. Delayed repair allows histological
      confirmation of complete excision and assists further resection if required.
      Preservation of healthy tissue is maximised allowing less radical reconstructive
      surgery without resorting to Mohs' labour intensive technique.

PMID- 14977770
TI  - Functional results and complications of Mersilene mesh use for frontalis
      suspension ptosis surgery.
AB  - AIMS: To assess the functional results and complications of Mersilene (polyester)
      mesh frontalis sling suspension to correct poor levator function ptosis. METHODS:
      Retrospective case series. 32 eyelids of 20 patients (12 children and eight
      adults). RESULTS: Follow up 1-69 months (mean 32). CHILDREN: eight patients had
      bilateral and four unilateral surgery (20 eyelids). Good long term functional
      results were achieved in 73% (8/11 children) and 77% (14/18) eyelids. Two
      children had early postoperative wound infection requiring removal of mesh in
      one; the other was lost to follow up following medical treatment. ADULTS: four
      patients had bilateral and four unilateral surgery (12 eyelids). Good long term
      functional results were achieved in 75% (6/8 patients, 9/12 eyelids). One
      postoperative wound infection and one mesh exposure were treated definitively by
      surgical excision of mesh. CONCLUSION: Mersilene mesh provides good functional
      results but up to 20% of patients have early soft tissue complications. Other
      materials such as monofilament suture or autogenous fascia lata should be
      considered.

PMID- 14977771
TI  - Causes of visual impairment in people aged 75 years and older in Britain: an add
      on study to the MRC Trial of Assessment and Management of Older People in the
      Community.
AB  - BACKGROUND: Visual impairment and blindness are common in older people in
      Britain. It is important to know the causes of visual impairment to develop
      health service and research priorities. The authors aimed to identify the causes
      of visual impairment in people aged 75 years and older in Britain. METHODS: In
      the MRC Trial of the Assessment and Management of Older People in the Community,
      trial nurses tested visual acuity in everyone aged 75 years and older in 53
      general practices. For all visually impaired patients in 49 of the 53 medical
      practices, data regarding the cause of vision loss were extracted from the
      general practice medical notes. Additional follow up questionnaires were also
      sent to the hospital ophthalmologist to confirm the cause of vision loss. Visual
      impairment was defined as a binocular acuity of less than 6/18. RESULTS: There
      were 1742 (12.5%) people visually impaired in the 49 participating practices. Of
      these, 450 (26%) achieved a pinhole visual acuity in either eye of 6/18 or
      better. In these people, the principal reason for visual loss was considered to
      be refractive error. The cause of visual loss was available for 976 (76%) of the
      remaining 1292 visually impaired people identified. The main cause of visual loss
      was age related macular degeneration (AMD); 52.9% (95% confidence interval 49.2
      to 56.5) of people had AMD as a main or contributory cause. This was followed by
      cataract (35.9%), glaucoma (11.6%), myopic degeneration (4.2%), and diabetic eye
      disease (3.4%). CONCLUSIONS: A substantial proportion of visual impairment in our
      sample of older people in Britain can be attributed to remediable causes
      refractive error and cataract. There is considerable potential for visual
      rehabilitation in this age group. For the large proportion with macular
      degeneration, low vision services will be important.

PMID- 14977772
TI  - Late onset post-keratoplasty astigmatism in patients with keratoconus.
AB  - AIM: 10 eyes of 10 patients are reported where progression of keratoconus in the
      host cornea occurred more than 10 years after penetrating keratoplasty with
      resultant increase in astigmatism. The technique and results of graft refractive
      surgery in seven eyes are presented. METHODS: The clinical features and
      management of these patients were retrospectively analysed. Graft refractive
      surgery involved an incision at the graft-host junction adjacent to the host
      thinning with compressive resuturing. Astigmatic changes were calculated using
      vector analysis. RESULTS: There were seven men and three women with a mean age of
      41.2 years. The average age when undergoing penetrating keratoplasty in the
      affected eye was 28.4 years and the average time after penetrating keratoplasty
      until keratoconus appeared in the host cornea defined by host thinning was 13.5
      years. The mean cylinder power before host thinning was noted was 5.07 D (SD
      2.19) and the mean after host thinning was 11.0 D (2.53). The mean vector
      calculated disease induced astigmatism magnitude was 7.59 D (3.09). Graft
      refractive surgery was performed in seven eyes. The mean cylinder power before
      and after graft refractive surgery was 11.28 D (2.15) and 7.09 D (5.53)
      respectively. The surgically induced astigmatism vector magnitude was 7.36 D
      (4.88). CONCLUSION: Progression of keratoconus in the host cornea late after
      penetrating keratoplasty is characterised by a large astigmatic change where the
      flat axis of astigmatism passes through an area of host thinning visible on slit
      lamp examination. Compressive resuturing performed in the area of host thinning
      resulted in satisfactory reduction of astigmatism.

PMID- 14977773
TI  - Human preocular mucins reflect changes in surface physiology.
AB  - BACKGROUND/AIMS: Mucin function is associated with both peptide core and
      glycosylation characteristics. The authors assessed whether structural
      alterations occurring during mucin residence in the tear film reflect changes in
      ocular surface physiology. METHODS: Ocular surface mucus was collected from
      normal volunteers as N-acetyl cysteine (NAcCys) washes or directly from the
      speculum after cataract surgery. To assess the influence of surface health on
      mucins, NAcCys washings were also obtained from patients with symptoms, but no
      clinical signs of dry eye (symptomatics). Mucins were extracted in guanidine
      hydrochloride (GuHCl) with protease inhibitors. Buoyant density of mucin species,
      a correlate of glycosylation density, was followed by reactivity with anti
      peptide core antibodies. Mucin hydrodynamic volume was assessed by gel filtration
      on Sepharose CL2B. RESULTS: Surface fluid and mucus contained soluble forms of
      MUC1, MUC2, MUC4, and MUC5AC and also the same species requiring DTT
      solubilisation. Reactivity with antibodies to MUC2 and MUC5AC peaked at 1.3-1.5
      g/ml in normals, while dominated by underglycosylated forms in symptomatics.
      Surface mucins were predominantly smaller than intracellular species. MUC2 size
      distributions were different in symptomatics and normals, while those of MUC5AC
      were similar in these two groups. CONCLUSIONS: A reduction in surface mucin size
      indicates post-secretory cleavage. Dissimilarities in surface mucin glycosylation
      and individual MUC size distributions in symptomatics suggest changes in
      preocular mucin that might precede dry eye signs.

PMID- 14977774
TI  - Anti-Ro/SSA and anti-La/SSB autoantibodies in the tear fluid of patients with
      Sjogren's syndrome.
AB  - PURPOSE: To investigate the presence of anti-Ro/SSA and anti-La/SSB antibodies in
      the tear fluid and serum of patients with Sjogren's syndrome and to evaluate the
      association of these autoantibodies with the severity of keratoconjunctivitis
      sicca. METHODS: Tear fluid and serum were obtained from 28 patients with
      Sjogren's syndrome and 17 age matched normal control subjects. Evaluation of tear
      fluid and sera anti-Ro/SSA and anti-La/SSB levels was done by using a
      quantitative enzyme linked immunosorbent assay kit designed for the quantitative
      measurement of IgG class autoantibodies directed against highly purified SSA and
      SSB antigens. Tear function and ocular surface were evaluated by Schirmer I test,
      tear break up time, and rose bengal staining. Dry eye symptom scores were
      recorded. RESULTS: Increased levels of anti-Ro/SSA and anti-La/SSB antibodies
      were detected in sera of 57.1% and 50% of SS patients, respectively. Six patients
      had increased levels of anti-Ro/SSA in the tear fluid, in one case anti-Ro/SSA
      being detected in tear fluid when it was negative in serum. Ten patients had
      positive anti-La/SSB titres in tear fluid and in four of these patients, anti
      La/SSB titres were not elevated in serum. A positive correlation was observed
      between serum and tear fluid titres of anti-Ro/SSA (r = 0.43, p = 0.02), but not
      of anti-La/SSB. Serum anti-Ro/SSA and anti-La/SSB concentrations correlated
      positively with dry eye symptom scores (r = 0.42, p = 0.02 and r = 0.48, p =
      0.01, respectively) and negatively correlated with Schirmer I test scores (r = 
      0.39, p = 0.04 and r = -0.40, p = 0.03, respectively). Significant correlations
      were found between tear anti-La/SSB concentrations and dry eye symptom score (r =
      0.56, p = 0.02) and also rose bengal staining scores of the ocular surface (r =
      0.44, p = 0.02). CONCLUSION: This study shows that autoantibodies against Ro/SSA
      and La/SSB antigens are present in the tear fluid of some patients with SS and
      their presence in serum or tear fluid is associated with the severity of
      keratoconjunctivitis sicca. Additional measurement of tear fluid levels of anti
      Ro/SSA and anti-La/SSB may serve as a valuable diagnostic indicator of SS.

PMID- 14977775
TI  - Clinical characteristics of conjunctivochalasis with or without aqueous tear
      deficiency.
AB  - AIM: To show characteristic ocular surface findings caused by conjunctivochalasis
      (CCh) in dry eye patients with or without aqueous tear deficiency (ATD). DESIGN:
      Comparative non-interventional cases. PATIENTS AND METHODS: Clinical data of five
      ATD patients without CCh (group A), eight CCh patients with ATD (group B), and
      eight CCh patients without ATD (group C) were retrospectively reviewed. Presence
      or absence of CCh was determined by fluorescein staining to outline tear meniscus
      and conjunctival folds with an enhancing filter. Dry eye symptoms, history of
      subconjunctival haemorrhage, meibum expression, tear break up time, fluorescein
      and rose bengal staining, and fluorescein clearance test, and other abnormal
      ocular surface findings were measured. RESULTS: CCh patients were significantly
      older (p = 0.001). In pure ATD, the principal symptom of dryness became worse as
      the day progressed. In contrast, blurry vision, burning sensation, and dryness
      became worse during reading in all CCh patients (p = 0.0008) or worse in the
      morning upon awakening in the majority patients with CCh only (p = 0.02). Besides
      the interpalpebral exposure, which was noted in ATD, positive fluorescein or rose
      bengal staining was noted in the redundant conjunctival folds and the non
      exposure zone in CCh (p = 0.0008). Redundant conjunctival folds were present in
      both lower and upper bulbar conjunctiva, obliterating both lower and upper tear
      meniscuses, and spatially correlated with anterior migration of the mucocutaneous
      junction in CCh. Delayed tear clearance was significantly more prevalent in CCh
      than ATD (p = 0.0008). Vigorous blinking worsened in CCh but not in ATD (p =
      0.0008). Lacrimal puncta were swollen in groups B and C, but not in group A (p =
      0.04). CONCLUSIONS: CCh is not restricted to the lower bulbar conjunctiva, and
      contributes to pathogenesis of dry eye by obliterating both lower and upper tear
      meniscus, causing unstable tear film and by creating delayed tear clearance. Dry
      eye symptoms were worsened by downgaze during reading and by vigorous blinking.
      Other characteristic signs including subconjunctival haemorrhage, swollen puncta,
      anterior migration of the mucocutaneous junction, and patterns of dye staining
      also help distinguish dry eye associated with CCh from that caused by ATD alone.

PMID- 14977776
TI  - Epithelial cell characteristics of cultured human limbal explants.
AB  - AIM: To determine the immunohistochemical characteristics of putative corneal
      epithelial stem cells remaining on limbal explants maintained in culture.
      METHODS: Human limbal explant cultures were generated from 25 residual
      corneoscleral donor rims following penetrating keratoplasty. Serial sections of
      these explants were studied using immunohistochemical techniques with a panel of
      antibodies, on day 0 and 1, 2, and 3 weeks. RESULTS: The number of epithelial
      cells expressing cytokeratin 19 and vimentin increased with duration in culture,
      while the number of cells expressing cytokeratin 3 decreased. Connexin 43
      expression was lost by 1 week in culture. p63 was expressed by cells that had
      migrated around the explant and the number of p63 positive cells decreased with
      longer duration in culture. The explants were initially negative for Ki67, but
      the epithelial cells were positive at 1 week, and expression of Ki67 was
      progressively lost with increasing duration in culture. The initial uniform
      staining of the epithelium for epidermal growth factor receptor and alpha enolase
      remained unchanged at 3 weeks. CONCLUSIONS: There is an expansion of less
      differentiated (cytokeratin 3 negative and CK19/vimentin positive) epithelial
      cells on corneoscleral explants maintained in culture for 3 weeks. The pattern of
      expression of p63 noted in this study does not support the suggestion that it is
      a marker of limbal stem cells. The decline in p63 and Ki67 expression among the
      epithelial cells of the cultured explant button implies that as the epithelial
      sheet outgrowing from the explant button reaches confluence, the proliferative
      status of the cells remaining on the explant button declines. These findings are
      of clinical relevance as explants of limbal tissue are used in limbal stem cell
      transplantation. There is no information available to date on the fate of
      epithelial cells on such explants. This study provides some insight into this and
      suggests that an expansion of the stem cell pool or its progeny may occur in
      limbal explants.

PMID- 14977777
TI  - T lymphocyte mediated lysis of mitomycin C treated Tenon's capsule fibroblasts.
AB  - AIMS: To evaluate the effect of T cell co-culture on mitomycin C treated and
      untreated Tenon's capsule fibroblasts. METHODS: IL-2 dependent allogeneic T cells
      were incubated over a monolayer of mitomycin C treated or control fibroblasts.
      Fibroblast numbers were evaluated by direct counts using phase contrast
      microscopy. To determine whether T cell mediated lysis was a consequence of MHC
      mismatch, co-culture experiments were repeated with autologous T cells. The
      effect of Fas receptor blockade was established by co-incubation with a Fas
      blocking (M3) antibody. RESULTS: T cell co-culture resulted in a dramatic
      reduction in fibroblast survival compared to mitomycin C treatment alone (p =
      0.032). T cell killing required fibroblast/lymphocyte cell to cell contact and
      was observed in both allogeneic and autologous co-culture experiments. Fas
      blocking antibodies did not significantly inhibit T cell killing (p = 0.39).
      CONCLUSION: T cells augment mitomycin C treated fibroblast death in vitro.
      Similar mechanisms may contribute to the cytotoxic effect of mitomycin C in vivo
      and account for the largely hypocellular drainage blebs that are observed
      clinically.

PMID- 14977778
TI  - Ocular haemodynamic responses to induced hypercapnia and hyperoxia in glaucoma.
AB  - AIM: To determine the ocular haemodynamic response to gas perturbations in
      glaucoma. METHODS: Intraocular pressure (IOP), systemic systolic and diastolic
      blood pressure (SBP and DBP), and retrobulbar blood flow velocities, measured by
      colour Doppler imaging (CDI), were recorded at two visits. CDI was used to
      measure peak systolic and end diastolic velocities (PSV and EDV) and resistance
      index (RI) in the ophthalmic artery (OA), central retinal artery (CRA), and short
      posterior ciliary arteries (SPCAs). At the first visit, measurements were taken
      at baseline (B1: breathing room air) and during isoxic hypercapnia (end tidal
      PCO(2) increased 15% above baseline) in 16 normal subjects and 12 patients with
      glaucoma. On another day, measurements were repeated at a second baseline (B2)
      and during hyperoxia (100% oxygen breathing) for 15 normal subjects and 13
      glaucoma patients. Baseline systemic data were compared using paired t tests;
      REANOVA was performed to compare group differences at baseline and to determine
      the vessel response to each condition. Fisher's LSD was used for post hoc
      comparison. RESULTS: Baseline OA PSV was lower for the glaucoma than for the
      normal group (p = 0.047); the groups were otherwise similar at baseline. IOP
      demonstrated no response to hypercapnia, but reduced during hyperoxia for both
      the normal subjects (p<0.0001) and glaucoma patients (p = 0.04). During
      hypercapnia, SBP increased in normal subjects (p = 0.03) and glaucoma patients (p
      = 0.01); DBP increased in normal subjects (p = 0.021). There was a corresponding
      increase in ocular perfusion pressure (OPP) for normal subjects (p = 0.01) and
      glaucoma subjects (p = 0.028), and as a result OPP was included as a covariate in
      the REANCOVA model. Hypercapnia resulted in increased PSV in the CRA of normal
      subjects (p = 0.035) and increased PSV and EDV in the SPCAs of glaucoma patients
      (p = 0.041 and p = 0.030 respectively). Hyperoxia resulted in reduced PSV and EDV
      in the ophthalmic arteries of normal subjects only (p = 0.001 and 0.031
      respectively). CONCLUSIONS: These findings suggest the presence of relative
      vasoconstriction in glaucoma patients, which is at least partially reversed by
      hypercapnia.

PMID- 14977779
TI  - Systemic CD4(+) T cell phenotype and activation status in intermediate uveitis.
AB  - AIM: To investigate peripheral blood lymphocyte phenotype in patients with
      intermediate uveitis using CD69, chemokine receptor, and cytokine expression.
      METHODS: Peripheral blood lymphocytes of 18 patients with idiopathic intermediate
      uveitis and 6 patients with presumed sarcoid intermediate uveitis were evaluated
      for CD4(+) T cell expression of CD69, CCR4, CCR5, CXCR3 and the intracellular
      cytokines IFNgamma, TNFalpha, and interleukin (IL)-10 by flow cytometry, and for
      IL-2, IL-4, IL-5, IL-10, IFNgamma, and TNFalpha production following unstimulated
      and activated culture using cytokine bead array and compared with healthy control
      subjects. RESULTS: The expression of CD69 and TNFalpha by peripheral blood CD4(+)
      lymphocytes of patients with idiopathic intermediate uveitis and presumed sarcoid
      intermediate uveitis was significantly higher than control subjects (p = 0.002
      and p<0.05, respectively). The ratios of the concentrations of IL-2:IL-5 and
      IFNgamma:IL-5 in supernatants of activated peripheral blood lymphocyte cultures
      were significantly higher in patients with presumed sarcoid intermediate uveitis
      than control subjects. CONCLUSIONS: This study implicates TNFalpha in the
      pathogenesis of intermediate uveitis, highlighting the potential role of anti-TNF
      treatments for this disease. Studies of Th1:Th2 cytokine ratios suggested
      polarisation of the immune response towards Th1 in presumed sarcoid intermediate
      uveitis despite clinically quiescent systemic disease.

PMID- 14977780
TI  - Use of preoperative assessment of positionally induced cyclotorsion: a video
      oculographic study.
AB  - PURPOSE: Positionally induced cyclotorsion could be an important factor
      concerning correction of astigmatism in refractive surgery. The method of
      binocular three dimensional infrared video-oculography (3D-VOG) was used to
      determine a possible influence of body position on cyclotorsion. METHODS: 38 eyes
      (19 healthy subjects, median value of age 25.5) with normal binocular vision were
      examined using 3D-VOG. This method records ocular motions and positions of both
      eyes simultaneously in the x, y, and z axis. Cycloposition of the eyes was
      recorded first in a seated position (both eyes open, test 1), then in a supine
      position (right eye closed, test 2), occlusion of both eyes (test 3), both eyes
      open (test 4). Cyclovergence was calculated as the difference between the right
      and the left eye positions. RESULTS: The range of cyclotorsion of the right and
      left eye in all four tests was between 1.13 degrees excyclotorsion and 0.34
      degrees incyclotorsion. There was no statistically significant difference of the
      median values for torsion for the four test situations. Concerning the influence
      of body position on cyclotorsion, a statistically significant difference between
      the different test positions and settings did not exist. Median values for
      right/left torsion/cyclovergence were: 0.17/0.04/0.02 (test 1), -0.31/-0.71/-0.16
      (test 2), -1.09/-0.60/0.82 (test 3), 0.28/0.28/-0.82 (test 4). CONCLUSIONS:
      Cyclotorsion does not significantly change between seated and supine position in
      subjects with normal binocular vision and stable fixation. In these subjects, an
      erroneous refractive surgery due to incorrect measurement of the axis of
      astigmatism in the seated position and performing the refractive surgery in the
      supine position, is very unlikely.

PMID- 14977781
TI  - Correlation of long term phenotypic and clinical outcomes following limbal
      epithelial transplantation cultivated on amniotic membrane in rabbits.
AB  - AIM: To determine the epithelial phenotype in rabbits with total limbal stem cell
      deficiency (LSCD) after reconstruction with autologous limbal epithelial stem
      cells ex vivo expanded on rabbit amniotic membrane (AM). METHODS: Left eyes of 52
      rabbits were rendered total LSCD, verified by impression cytology. The
      fibrovascular pannus of each cornea was removed. Group I (n = 10) received rabbit
      AM transplantation alone, while groups II-IV (n = 42) underwent transplantation
      of LSC cultured on rabbit AM (LSC-AM) from a small limbal biopsy taken from the
      right eye. Clinical outcome was graded as "success," "partial success," or
      "failure" depending on the corneal smoothness and avascularity. Epithelial
      phenotype was determined by immunostaining and graded as "corneal (K),"
      "conjunctival (J)," or "mixed (M)" depending on expression of K3 and Muc5AC.
      RESULTS: After 1 year follow up, group I showed 100% failure and groups II-IV
      showed 26% success (p<0.001). Clinical failure correlated with J phenotype p =
      0.001), while clinical success correlated with K phenotype p = 0.01). When the
      phenotypic outcome was used for comparison, J phenotype was significantly high in
      group I (p = 0.003), while K phenotype was significantly high in groups II-IV
      (p<0.05). CONCLUSION: There is a strong correlation between clinical success and
      resultant corneal epithelial phenotype. Ex vivo expanded LSC can successfully
      reconstruct corneal surfaces with unilateral total LSCD.

PMID- 14977782
TI  - Mouse genetic corneal disease resulting from transgenic insertional mutagenesis.
AB  - BACKGROUND/AIMS: To report the generation of a new mouse model for a genetically
      determined corneal abnormality that occurred in transgenesis experiments.
      METHODS: Transgenic mice expressing mutant forms of Rab27a, a GTPase that has
      been implicated in the pathogenesis of choroideremia, were generated. RESULTS:
      Only one transgenic line (T27aT15) exhibited an unexpected eye phenotype. T27aT15
      mice developed corneal opacities, usually unilateral, and cataracts, resulting in
      some cases in phthisical eyes. Histologically, the corneal stroma was thickened
      and vacuolated, and both epithelium and endothelium were thinned. The posterior
      segment of the eye was also affected with abnormal pigmentation, vessel
      narrowing, and abnormal leakage of dye upon angiography but was histologically
      normal. CONCLUSION: Eye abnormality in T27aT15 mice results from random
      insertional mutagenesis of the transgene as it was only observed in one line. The
      corneal lesion observed in T27aT15 mice most closely resembles posterior
      polymorphous corneal dystrophy and might result from the disruption of the
      equivalent mouse locus.

PMID- 14977783
TI  - Diabetic retinopathy: should this patient receive laser treatment?

PMID- 14977784
TI  - View 1: should this patient receive laser treatment?

PMID- 14977785
TI  - View 2: should this patient receive laser treatment?

PMID- 14977786
TI  - Diabetic retinopathy: should this patient receive laser treatment? Overview.

PMID- 14977787
TI  - Can antiseptic scrubs between cataract surgeries reduce bacterial load on
      surgical gloves to safe levels?

PMID- 14977788
TI  - Penetrating ocular injuries in previously injured blind eyes: should we consider
      primary enucleation?

PMID- 14977789
TI  - Practical solutions to service shortcomings in the care of older people: the case
      for professional collaboration.

PMID- 14977790
TI  - Sorsby fundus dystrophy presenting with choroidal neovascularisation showing good
      response to steroid treatment.

PMID- 14977792
TI  - Comparison of phenylephrine infusion regimens for maintaining maternal blood
      pressure during spinal anaesthesia for Caesarean section.
AB  - BACKGROUND: During spinal anaesthesia for Caesarean section, the optimal
      phenylephrine regimen and the optimal blood pressure (BP) to which it should be
      titrated are undetermined. The ideal regimen would balance efficacy for
      maintaining uteroplacental perfusion pressure against potential for
      uteroplacental vasoconstriction, both of which may affect fetal acid-base status.
      We compared phenylephrine infusion regimens based on three different BP
      thresholds. METHODS: After intrathecal injection, we infused phenylephrine 100
      microg min(-1) for 2 min. Then, until delivery, we infused phenylephrine whenever
      systolic BP (SBP), measured every 1 min, was below a randomly assigned percentage
      of baseline: 100% (Group 100, n=25), 90% (Group 90, n=25) or 80% (Group 80,
      n=24). We compared umbilical blood gases, Apgar scores and maternal haemodynamics
      and symptoms. RESULTS: Patients in Group 100 had fewer episodes [median 0 (range
      0-8)] of hypotension (SBP <80% baseline) compared with Group 80 [5 (0-18)] and
      Group 90 [2 (0-7)] (P<0.001 in each instance). Total dose of phenylephrine was
      greater in Group 100 [median 1520 microg (interquartile range 1250-2130 microg)]
      compared with Group 90 [1070 (890-1360) microg] and Group 80 [790 (590-950)
      microg]. Umbilical arterial pH was greater in Group 100 [mean 7.32 (95%
      confidence interval 7.31-7.34)] than in Group 80 [7.30 (7.28-7.31)] (P=0.034). No
      patient had umbilical arterial pH <7.2. In Group 100, 1/24 (4%) patients had
      nausea or vomiting compared with 4/25 (16%) in Group 90 and 10/25 (40%) in Group
      80 (P=0.006). CONCLUSIONS: For optimal management, phenylephrine should be
      titrated to maintain maternal BP at near-baseline values.

PMID- 14977793
TI  - Agitation and changes of Bispectral Index and electroencephalographic-derived
      variables during sevoflurane induction in children: clonidine premedication
      reduces agitation compared with midazolam.
AB  - BACKGROUND: This double-blind randomized study was undertaken to assess
      agitation, Bispectral Index (BIS) and EEG changes during induction of anaesthesia
      with sevoflurane in children premedicated with midazolam or clonidine. METHODS:
      Children were allocated randomly to receive rectal midazolam 0.4 mg kg(-1) (n=20)
      or oral clonidine 4 microg kg(-1) (n=20) as premedication. Rapid induction of
      anaesthesia was achieved with inhalation of sevoflurane 8% in nitrous oxide 50%
      oxygen 50%. After tracheal intubation, the children's lungs were mechanically
      ventilated and the inspired sevoflurane concentration was adjusted to achieve an
      end-tidal fraction of 2.5%. The EEG and BIS were recorded during induction until
      10 min after tracheal intubation. The EEG was analysed using spectral analysis at
      five points: baseline, loss of eyelash reflex, 15 s before the nadir of the BIS
      (BIS(nadir)), when both pupils returned to the central position (immediately
      before intubation), and 10 min after intubation. RESULTS: Agitation was observed
      in 12 midazolam-treated and five clonidine-treated patients (P=0.05). At
      baseline, EEG rhythms were slower in the clonidine group. Induction of
      anaesthesia was associated with similar EEG changes in the two groups, with an
      increase in total spectral power and a shift towards low frequencies; these
      changes were maximal around the end of the second minute of induction
      (BIS(nadir)). When the pupils had returned to the central position, fast EEG
      rhythms increased and BIS was higher than BIS(nadir) (P<0.05). In both groups,
      agitation was associated with an increase in slow EEG rhythms at BIS(nadir).
      CONCLUSIONS: Compared with midazolam, clonidine premedication reduced agitation
      during sevoflurane induction. During induction with sevoflurane 8% (oxygen 50%
      nitrous oxide 50%), the nadir of the BIS occurred at the end of the second minute
      of inhalation. Agitation was associated with a more pronounced slowing of the EEG
      rhythms at BIS(nadir) compared with inductions in which no agitation was
      observed. The BIS may not follow the depth of anaesthesia during sevoflurane
      induction in children.

PMID- 14977794
TI  - Volume kinetics of glucose 2.5% solution during laparoscopic cholecystectomy.
AB  - BACKGROUND: Analyses of the distribution and elimination of glucose 2.5%
      solutions can be used to suggest combinations of infusion rates and infusion
      times which yield a predetermined plasma glucose level and degree of plasma
      dilution during surgery. METHODS: Twelve patients aged between 27 and 51 (mean
      40) underwent laparoscopic cholecystectomy. An i.v. infusion of 1.4 litres of
      glucose 2.5% over 60 min was started when surgery began. A volume kinetic model
      was fitted to measurements of the plasma glucose concentration and the degree of
      haemodilution. Nomograms were constructed based on the kinetic results. RESULTS:
      The volume of distribution for the glucose and infused fluid and the plasma
      insulin levels were similar to the ones recorded in previous volunteer studies,
      but 50-70% lower values were obtained for the clearance of glucose (mean 0.21
      litres min(-1)), endogenous glucose production (1.1 mmol min(-1)) and the
      elimination rate constant for the infused fluid (median 37 ml min(-1)). Urinary
      excretion was markedly depressed and amounted to 9% of the infused fluid volume 4
      h after starting surgery. To prevent hyperglycaemia, nomograms suggested that the
      infusion should be directed towards a "target" glucose concentration and then
      slowed down in a controlled way. At steady state, the infused fluid maintains a
      3.5% plasma dilution for each mmol that plasma glucose remains above baseline.
      CONCLUSION: Metabolic changes warrant careful balancing of infusion rates of
      glucose 2.5% during laparoscopic cholecystectomy, which is facilitated by a
      nomogram. Volume expansion from the infused fluid volume should be recognized.

PMID- 14977795
TI  - Prevalence of postoperative bladder distension and urinary retention detected by
      ultrasound measurement.
AB  - BACKGROUND: Postoperative bladder distension and urinary retention are commonly
      underestimated. Ultrasound enables accurate measurement of bladder volume and
      thus makes it possible to determine the prevalence of postoperative bladder
      distension. METHODS: Using ultrasound, we measured the volume of the bladder
      contents at the time of discharge from the recovery room in 177 adult patients
      who had undergone thoracic, vascular, abdominal, orthopaedic or ENT surgery.
      RESULTS: Forty-four per cent of the patients had a bladder volume >500 ml and 54%
      of the 44%, who had no symptoms of bladder distension, were unable to void
      spontaneously within 30 min. The risk factors for urinary retention were age >60
      yr (odds ratio (OR) 2.11, 95% confidence interval (CI) 1.01-4.38), spinal
      anaesthesia (OR 3.97, 95% CI 1.32-11.89) and duration of surgery >120 min (OR
      3.03, 95% CI 1.39-6.61). CONCLUSION: Before discharge from the recovery room it
      seems worthwhile to systematically check the bladder volume with a portable
      ultrasound device in patients with risk factors.

PMID- 14977796
TI  - Cardioprotective effects of desflurane: effect of timing and duration of
      administration in rat myocardium.
AB  - BACKGROUND: We compared the cardioprotective effects of 1 minimum alveolar
      concentration (MAC) desflurane administered before, during or after ischaemia, or
      throughout the experiment (before, during and after ischaemia) on myocardial
      infarct size following 30 min occlusion of the left anterior descending coronary
      artery and 3 h reperfusion in adult rats. METHODS: Fifty male Sprague-Dawley rats
      were anaesthetized with pentobarbital, intubated and mechanically ventilated.
      Blood gases, pH and body temperature (37.5-38 degrees C) were controlled. Heart
      rate and arterial pressure were measured continuously. Animals were randomly
      assigned to the following groups (n=10 in each group): pentobarbital only
      ("Pento"); 15 min desflurane administration followed by 10 min of washout before
      30 min ischaemia and 3 h reperfusion ("Precond"); 30 min desflurane
      administration during ischaemia period ('Isch'); desflurane administration during
      the 15 first min of reperfusion ("Reperf") and desflurane administration
      throughout the experiment (before, during and after ischaemia; "Long"). Volumes
      at risk and infarct sizes were assessed by Indian ink and with 2,3,5
      triphenyltetrazolium chloride staining, respectively. RESULTS: Physiological
      parameters and volumes at risk were not significantly different between groups.
      In the Pento group, mean myocardial infarct size was 65 (sd 15)% of the volume at
      risk; myocardial infarct size was reduced to a significant and comparable extent
      in the desflurane-treated groups (Precond 42 (14)%; Isch 34 (11)%; Reperf 41
      (15)%; Long 33 (10)%; P<0.0002 vs Pento group). CONCLUSIONS: In rats, desflurane
      1 MAC significantly decreased myocardial infarct size whatever the period and
      duration of administration.

PMID- 14977797
TI  - Effect of re-expansion after short-period lung collapse on pulmonary capillary
      permeability and pro-inflammatory cytokine gene expression in isolated rabbit
      lungs.
AB  - BACKGROUND: Re-expansion pulmonary oedema is a rare complication caused by rapid
      re-expansion of a chronically collapsed lung. Several cases of pulmonary oedema
      associated with one-lung ventilation (OLV) have been reported recently. Elevated
      levels of pro-inflammatory cytokines in pulmonary oedema fluid are suggested to
      play important roles in its development. Activation of cytokines after re
      expansion of collapsed lung during OLV has not been thoroughly investigated. Here
      we investigated the effects of re-expansion of the collapsed lung on pulmonary
      oedema formation and pro-inflammatory cytokine expression. METHODS: Lungs
      isolated from female white Japanese rabbits were perfused and divided into a
      basal (BAS) group (n=7, baseline measurement alone), a control (CONT) group (n=9,
      ventilated without lung collapse for 120 min) and an atelectasis (ATEL) group
      (n=9, lung collapsed for 55 min followed by re-expansion and ventilation for 65
      min). Pulmonary vascular resistance (PVR) and the coefficient of filtration (Kfc)
      were measured at baseline and 60 and 120 min. At the end of perfusion,
      bronchoalveolar lavage fluid/plasma protein ratio (B/P), wet/dry lung weight
      ratio (W/D) and mRNA expressions of tumour necrosis factor (TNF)-alpha,
      interleukin (IL)-1beta and myeloperoxidase (MPO) were determined. RESULTS: TNF
      alpha and IL-1beta mRNA were significantly up-regulated in lungs of the ATEL
      group compared with BAS and CONT, though no significant differences were noted in
      PVR, Kfc, B/P and W/D within and between groups. MPO increased at 120 min in CONT
      and ATEL groups. CONCLUSION: Pro-inflammatory cytokines were up-regulated upon re
      expansion and ventilation after short-period lung collapse, though no changes
      were noted in pulmonary capillary permeability.

PMID- 14977798
TI  - EEG-controlled closed-loop dosing of propofol in rats.
AB  - BACKGROUND: Based on previous pharmacokinetic and pharmacodynamic studies, we
      have developed an EEG-controlled closed-loop system for the i.v. hypnotic agent
      propofol in rats. METHODS: Seven adult male Sprague-Dawley rats (weight 423-584
      g) were included in the study. EEG was recorded with occipito-occipital needle
      electrodes and the EEG power spectrum was estimated. The median frequency (MEF)
      was extracted from the power spectrum and was modified MEF (mMEF) to account for
      the occurrence of spikes and burst suppression patterns in the EEG. Propofol
      infusion was controlled by a model-based adaptive control algorithm to maintain a
      set point of mMEF=3.0 (sd 0.5) Hz. The performance of the feedback system was
      characterized by the median performance error MDPE=median[(mMEF-set point)/set
      point] and the median absolute performance error (MDAPE). The effective
      therapeutic infusion (ETI) to maintain the set point was determined from the
      resulting infusion rates. RESULTS: In all rats a feedback period of 90 min could
      be performed. Mean MDPE was 1.2 (se 0.4)% and MDAPE was 13.9 (0.3)%. The ETI was
      0.73 (sd 0.20) mg kg(-1) min(-1). Mean arterial pressure before propofol infusion
      was 148 (14) mm Hg, with the lowest value during closed-loop infusion being 110
      (20) mm Hg. CONCLUSIONS: The feedback system presented here may be a useful tool
      not only for automatic drug control to maintain a defined hypnotic effect but may
      also be a powerful device in pharmacological studies such as the determination of
      dose requirements or the assessment of drug-drug interactions.

PMID- 14977799
TI  - Glass recycling in the labour suite is environmentally sound and economical.
AB  - BACKGROUND: Glass bottles are used for the storage of local anaesthetics in the
      US and are recyclable. Recycling would result in hospital solid waste reduction.
      METHODS: The members of the Department of Anaesthesia were surveyed to determine
      where these local anaesthetic bottles were disposed of. From November 2002 to
      April 2003, glass bottles used on the labour and delivery suite were saved for
      recycling. The number of bottles and the weight recycled were recorded. The
      number of procedures involving anaesthesia were also recorded during this time
      period. RESULTS: Residents dispose of the local anaesthetic bottle in the sharps
      container while consultants dispose of them in the trash (P<0.05). Both means of
      disposal are not recycled in the US. The average amount of glass recycled per
      month was 19.37 (3.15) kg. Our hospital pays $0.46/kg (0.26 UK pound/kg) for
      sharps disposal. By not disposing of the glass in the sharps container, the
      average savings per month was $8.95 (1.45) (5.15 UK pounds (0.84)). CONCLUSION:
      The recycling of glass is good for the environment through waste reduction and
      results in small savings to the hospital.

PMID- 14977800
TI  - A fine balance--one-lung ventilation in a patient with Eisenmenger syndrome.
AB  - A 38-yr-old woman with an atrial septum defect and Eisenmenger syndrome was
      scheduled for a lung biopsy via thoracoscopy during one-lung ventilation. Fluids
      were given to increase central venous pressure to 8 mm Hg, an epidural catheter
      was inserted at the sixth thoracic intervertebral space and ropivacaine 0.3%, 6
      ml were given. Careful balance of systemic and pulmonary vascular resistance is
      crucial in Eisenmenger syndrome, so norepinephrine (0.14 mg kg(-1) min(-1)) was
      infused before general anaesthesia was started with fentanyl 4 mg kg(-1),
      ketamine 2 mg kg(-1), pancuronium 1 mg and succinylcholine 2 mg kg(-1).
      Anaesthesia was maintained with propofol 4-8 mg kg(-1) h(-1). To control
      pulmonary artery pressure, ventilation was performed with oxygen 100% and nitric
      oxide 20 ppm. Surgery and anaesthesia course were uneventful and the patient was
      extubated. However, pleural haemorrhage required treatment with blood components,
      re-intubation on the second postoperative day and removal of the haematoma by
      mini-thoracotomy. A step-by-step approach using a balanced combination of
      regional and general anaesthesia, controlled fluid administration, norepinephrine
      and inhaled nitric oxide preserved a stable circulation even during one-lung
      ventilation. The diagnostic value of lung biopsy must be weighed against the
      possibility of life-threatening haemorrhage.

PMID- 14977801
TI  - Bilateral subcapital neck of femur fractures after eclamptic seizures.
AB  - A previously healthy female sustained bilateral subcapital femur fractures during
      an eclamptic seizure. This complication has not been previously described in
      association with eclampsia. Clinicians need to be aware of this potential
      complication and investigate postseizure hip pain appropriately.

PMID- 14977802
TI  - Rocuronium for muscle relaxation in two children with Friedreich's ataxia.
AB  - Friedreich's ataxia is a rare hereditary neurodegenerative disease caused by a
      defect in the gene that encodes a mitochondrial protein called frataxin. We
      report the use of rocuronium 0.6 mg kg(-1) in two adolescent girls with
      Friedreich's ataxia undergoing propofol-sufentanil-oxygen-air anaesthesia for
      spinal surgery. Neuromuscular transmission was monitored using acceleromyography,
      and onset and recovery times were recorded. The clinical duration of rocuronium
      was comparable to that of children without neuromuscular disease (25% recovery
      T(1)=44 and 24 min for patients 1 and 2 respectively).

PMID- 14977803
TI  - Effect of rofecoxib on platelet aggregation and blood loss in gynaecological and
      breast surgery compared with diclofenac.
AB  - BACKGROUND: Non-selective cyclooxygenase (COX) inhibitors or non-steroidal anti-
      inflammatory drugs (NSAIDs) are frequently omitted for perioperative pain relief
      because of potential side-effects. COX-2-selective inhibitors may have a more
      favourable side-effect profile. This study tested the hypothesis that the COX-2
      selective inhibitor rofecoxib has less influence on platelet function than the
      NSAID diclofenac in gynaecological surgery. In addition, analgesic efficacy and
      side-effects of the two drugs were compared. METHODS: In this single-centre,
      prospective, double-blind, active controlled study, women undergoing vaginal
      hysterectomy (n=25) or breast surgery (n=25) under general anaesthesia received
      preoperatively 50 mg of rofecoxib p.o. followed 8 and 16 h later by two doses of
      placebo or three doses of diclofenac 50 mg p.o. at the same time points. We
      assessed arachidonic acid-stimulated platelet aggregation before and 4 h after
      the first dose of study medication, estimated intraoperative blood loss, and
      haemoglobin loss until the first morning after surgery. Analgesic efficacy, use
      of rescue analgesics, and side-effects were also recorded. RESULTS: In the
      rofecoxib group, stimulated platelet aggregation was disturbed less (P=0.02), and
      estimated intraoperative blood loss (P=0.01) and the decrease in haemoglobin were
      lower (P=0.01). At similar pain ratings, the use of anti-emetic drugs was less in
      the rofecoxib group (P=0.03). CONCLUSION: Besides having a smaller effect on
      platelet aggregation, one oral dose of rofecoxib 50 mg given before surgery
      provided postoperative analgesia similar to that given by three doses of
      diclofenac 50 mg and was associated with less use of anti-emetics and less
      surgical blood loss in gynaecological surgery compared with diclofenac.

PMID- 14977805
TI  - Behavioral responses of newly hatched zebrafish (Danio rerio) to amino acid
      chemostimulants.
AB  - The zebrafish chemosensory systems of olfaction, taste and solitary chemosensory
      cells (SCCs) are established during the first week after fertilization (a.f.).
      These systems presumably support the early development of feeding behaviors
      required as yolk supplies diminish over the same period. Yet there is no previous
      data reporting early chemosensory responses in zebrafish. We therefore assayed
      the chemosensory behavior of newly hatched zebrafish on days 3, 4 and 5 a.f.
      Responses were compared between fish exposed to water alone versus water
      containing a mixture of 12 amino acids (100 microM each) flowing through a 50 ml
      test chamber at 4 ml/min; computer-assisted motion analysis was used to quantify
      responses. Behavioral responses were first observed at day 4 a.f.; the number of
      fish swimming, their swimming speeds, and their net-to-gross displacement (NGDR)
      all increased significantly in response to amino acid stimulation. Because taste
      buds first appear 4-5 days a.f. and the SCCs may not respond to amino acids,
      these initial chemosensory responses of day 4 fish may be mediated by already
      established olfactory neurons. The onset of chemosensitivity in day 4 fish
      corresponded with an easily recognizable developmental phenotype of inactive
      floating; day 3 fish were inactive and resting on the bottom while day 5 fish
      were active and moving through the water column. The ease of identifying
      responsive day 4 fish suggests these animals may be useful for characterizing
      odorant sensitivity or developmental plasticity or for screening for chemosensory
      mutations.

PMID- 14977806
TI  - Olfactory sensitivity for carboxylic acids in spider monkeys and pigtail
      macaques.
AB  - Using a conditioning paradigm, the olfactory sensitivity of four spider monkeys
      and four pigtail macaques for a homologous series of carboxylic acids (n
      propionic acid to n-heptanoic acid) was investigated. With only few exceptions,
      the animals of both species significantly discriminated concentrations <1 p.p.m.
      from the odorless solvent and in several cases individual monkeys even
      demonstrated thresholds <1 p.p.b. The results showed (i). both primate species to
      have a well-developed olfactory sensitivity for carboxylic acids, which for some
      substances matches or even is markedly better than that of species such as the
      rat or the dog and (ii). a significant correlation between perceptibility in
      terms of olfactory detection thresholds and carbon chain length of the carboxylic
      acids in both species tested. These findings lend further support to the growing
      body of evidence suggesting that between-species comparisons of the number of
      functional olfactory receptor genes or of neuroanatomical features are poor
      predictors of olfactory performance, and that general labels such as 'microsmat'
      or 'macrosmat'-which usually are based on allometric comparisons of olfactory
      brain structures-are inadequate to describe a species' olfactory capabilities.

PMID- 14977807
TI  - Melanocortin-5 receptor deficiency reduces a pheromonal signal for aggression in
      male mice.
AB  - Mice lacking the melanocortin-5 receptor (MC5R) exhibit decreased sensitivity to
      the stimulatory effects of systemic melanocortin injections on aggressive
      behavior. Because the pheromone-producing preputial gland expresses the MC5R, we
      tested the hypothesis that decreases in preputial pheromones underlie the
      behavioral deficit. Here we show that MC5R deficiency decreases preputial and
      urine levels of the sex pheromones, alpha- and beta-farnesene, relative to wild
      type mice. We also demonstrate that farnesenes potently stimulate aggression in
      mice. Moreover, farnesene-stimulated aggression is reduced in MC5R-deficient
      mice, relative to wild-type mice. Our results suggest that activation of the MC5R
      promotes aggression by increasing farnesene signaling.

PMID- 14977808
TI  - Pheromone-binding proteins contribute to the activation of olfactory receptor
      neurons in the silkmoths antheraea polyphemus and Bombyx mori.
AB  - The sensilla trichodea of the silkmoth Antheraea polyphemus are innervated by
      three types of receptor neurons each responding specifically to one of three
      pheromone components. The sensillum lymph of these sensilla surrounding the
      sensory dendrites contains three different types of pheromone-binding proteins
      (PBPs) in high concentrations. The sensilla trichodea of the silkmoth Bombyx mori
      are supplied by two receptor neurons each tuned specifically to one of the two
      pheromone components bombykol and bombykal, but only one type of PBP has been
      found so far in these sensilla. Recombinant PBPs of both silkmoth species in
      various combinations with pheromone components were applied to the receptor
      neurons via tip-opened sensilla during electrophysiological recordings. Over a
      fairly broad range of pheromone concentrations the responses of the receptor
      neurons depended on both, the pheromone component and the type of the PBP.
      Therefore, the PBPs appear to contribute to the excitation of the receptor
      neurons. Furthermore, bombykal in combination with the expressed PBP of B. mori
      failed to activate the corresponding receptor neuron of B. mori, but did so if
      combined with one of the PBPs of A. polyphemus. Therefore, a still unknown
      binding protein involved in bombykal transport might be present in B. mori.

PMID- 14977809
TI  - Different thresholds for detection and discrimination of odors in the honey bee
      (Apis mellifera).
AB  - Naturally occurring odors used by animals for mate recognition, food
      identification and other purposes must be detected at concentrations that vary
      across several orders of magnitude. Olfactory systems must therefore have the
      capacity to represent odors over a large range of concentrations regardless of
      dramatic changes in the salience, or perceived intensity, of a stimulus. The
      stability of the representation of an odor relative to other odors across
      concentration has not been extensively evaluated. We tested the ability of honey
      bees to discriminate pure odorants across a range of concentrations at and above
      their detection threshold. Our study showed that pure odorant compounds became
      progressively easier for honey bees to discriminate with increasing
      concentration. Discrimination is, therefore, a function of odorant concentration.
      We hypothesize that the recruitment of sensory cell populations across a range of
      concentrations may be important for odor coding, perhaps by changing its
      perceptual qualities or by increasing its salience against background stimuli,
      and that this mechanism is a general property of olfactory systems.

PMID- 14977810
TI  - Temporal integration in nasal lateralization and nasal detection of carbon
      dioxide.
AB  - Two experiments examined time/concentration trading for the detection of carbon
      dioxide, an irritant with little or no odor. Experiment 1 employed the nasal
      lateralization method: subjects attempted to determine which nostril received
      carbon dioxide and which received pure air when presented simultaneously.
      Experiment 2 employed a temporal, two-alternative, forced-choice, detection
      paradigm with monorhinal stimulation. In both experiments, stimulus duration was
      varied at a number of fixed concentrations to determine the shortest, detectable
      pulse. Under both conditions, threshold pulse duration decreased as stimulus
      concentration increased. Power functions with exponents of less than negative one
      described the data quite well: More than a twofold increase in duration was
      needed to compensate for a twofold decrease in concentration. Thus, for carbon
      dioxide, the nasal trigeminal system functions as an imperfect integrator at
      threshold-level.

PMID- 14977811
TI  - Olfactory discrimination ability of human subjects for enantiomers with an
      isopropenyl group at the chiral center.
AB  - The ability of 20 human subjects to distinguish between nine enantiomeric odor
      pairs sharing an isopropenyl group at the chiral center was tested in a forced
      choice triangular test procedure. I found (i). that as a group, the subjects were
      only able to significantly discriminate the optical isomers of limonene, carvone,
      dihydrocarvone, dihydrocarveol and dihydrocarvyl acetate, whereas they failed to
      distinguish between the (+)- and (-)-forms of perillaalcohol, perillaaldehyde,
      isopulegol and limonene oxide; (ii). marked interindividual differences in
      discrimination performance, ranging from subjects who were able to significantly
      discriminate between eight of the nine odor pairs to subjects who failed to do so
      with six of the nine tasks; and (iii). that with none of the nine odor pairs the
      antipodes were reported to differ significantly in subjective intensity when
      presented at equal concentrations. Additional tests of the chemesthetic potency
      and threshold measurements of the optical isomers of dihydrocarvone,
      dihydrocarveol, and dihydrocarvyl acetate suggest that the discriminability of
      these three enantiomeric odor pairs is indeed due to differences in odor quality.
      Analysis of structure-activity relationships suggest that the combined presence
      of (i). an isopropenyl group at the chiral center; (ii). a methyl group at the
      para-position; and/or (iii). an oxygen-containing group at the meta-position
      allows for the discrimination of enantiomeric odor pairs.

PMID- 14977812
TI  - In vitro study of the influence of physiological parameters on dynamic in-mouth
      flavour release from liquids.
AB  - Influences of shear rate (surface extension), airflow, in-mouth headspace volume,
      synthetic saliva and human epithelial cells (modelling mucosa) on the initial
      dynamic flavour release from liquids were analysed. Simulating physiological
      mouth parameters, initial dynamic flavour release experiments over a time period
      of 30 s were carried out using a proven mouth model apparatus. Flavour compounds
      of different chemical classes were dissolved in water or in aqueous starch
      hydrolysate in concentrations typically present in food ( micro g/l to mg/l).
      Forced by increasing shear rates the enlargement of the gas-liquid interface
      (vortex formation) caused an increased release of flavour molecules. The release
      of less soluble compounds was reduced by increasing shear forces due to an
      improved dissolution. Increasing volumetric airflow rates resulted generally in
      higher release rates and in a change of pattern of release kinetics. Maximum
      flavour release was found at a ratio of 1:1 for in-mouth headspace and liquid
      volume. Neither addition of saliva alone nor the combination of saliva and mucosa
      showed significant influence on in-mouth flavour release from liquids in the
      model mouth.

PMID- 14977813
TI  - Volatile release from liquids: a comparison of in vivo APCI-MS, in-mouth
      headspace trapping and in vitro mouth model data.
AB  - In-mouth volatile release from flavoured water was followed using atmospheric
      pressure chemical ionization-mass spectrometry (APCI-MS) or using a hand-held,
      computer-controlled device based on sequential trapping of flavours on Tenax
      traps. The present results verify recent in vitro data obtained with a
      sophisticated, fully computerized mouth model apparatus and confirm its validity
      for the simulation of in-mouth dynamic volatile release. In-nose APCI-MS
      measurements showed considerable person-to-person variability in non-trained
      individuals during drinking due to subconscious control of muscles during
      swallowing and subsequent breathing. Data showed a 'swallow breath' volume
      reaching the nasal cavity from the throat, not from the mouth cavity. Flavour
      enriched air from the mouth was shown to be transported to the nose (via
      exhalation) immediately after the swallowing event, but the dynamic process of
      volatile equilibration between residuals of the swallowed liquid and the exhaled
      air predominantly determined volatile in-nose concentration. Owing to its dynamic
      character, the process of volatile equilibration and release in the throat upon
      exhalation should be similar to the in-mouth process studied in the present work.
      A full mechanical simulation of retronasal volatile transport, however, will
      remain difficult.

PMID- 14977815
TI  - Targeting cancer with telomerase: commentary re Q. Huang et al., a novel
      conditionally replicative adenovirus vector targeting telomerase-positive tumor
      cells. Clin. Cancer Res., 10: 1439-1445, 2004.

PMID- 14977816
TI  - Evaluating antiangiogenesis agents in the clinic: the Eastern Cooperative
      Oncology Group Portfolio of Clinical Trials.
AB  - Recent evidence indicates that treatment with a humanized monoclonal antibody
      (bevacizumab) directed at vascular endothelial growth factor improves response
      and survival in metastatic colorectal cancer when added to standard chemotherapy,
      validating angiogenesis as a therapeutic target. Investigators from the Eastern
      Cooperative Oncology Group (ECOG) have initiated a number of Phase III studies
      that will help further define the role of antiangiogenic agents for the treatment
      of breast, colon, lung, renal, and head and neck cancer, as well as melanoma and
      myeloma. The agents being evaluated target various biological functions involved
      in angiogenesis, including vascular endothelial growth factor (bevacizumab),
      endothelial cell proliferation (thalidomide, IFN-alpha), and matrix
      metalloproteinases (marimastat). These clinical trials include correlative
      laboratory studies aimed at elucidating how these agents may exert their clinical
      effects. The portfolio of Eastern Cooperative Oncology Group studies will serve
      to further define the role of this therapeutic strategy for patients with
      advanced cancer.

PMID- 14977817
TI  - United States Food and Drug Administration Drug Approval summary: Gefitinib
      (ZD1839; Iressa) tablets.
AB  - On May 5, 2003, gefitinib (Iressa; ZD1839) 250-mg tablets (AstraZeneca Inc.)
      received accelerated approval by the United States Food and Drug Administration
      as monotherapy for patients with locally advanced or metastatic non-small cell
      lung cancer after failure of both platinum-based and docetaxel chemotherapies.
      Information provided in this summary includes chemistry manufacturing and
      controls, clinical pharmacology, and clinical trial efficacy and safety results.
      Gefitinib is an anilinoquinazoline compound with the chemical name 4
      quinazolinamine,N-(3-chloro-4-flurophenyl)-7-methoxy-6-[3-(4
      morpholinyl)propoxy]. It has the molecular formula C(22)H(24)ClFN(4)O(3).
      Gefitinib is often referred to as a "specific" or "selective" inhibitor of
      epidermal growth factor receptor. Studies demonstrate, however, that gefitinib
      inhibits the activity of other intracellular transmembrane tyrosine-specific
      protein kinases at concentrations similar to those at which it inhibits the
      epidermal growth factor signal. Maximum plasma concentrations resulting from
      clinically relevant doses are 0.5-1 microM or more, well within the IC(50) values
      of several tyrosine kinases. No clinical studies have been performed that
      demonstrate a correlation between epidermal growth factor receptor expression and
      response to gefitinib. Gefitinib is 60% available after oral administration and
      is widely distributed throughout the body. Gefitinib is extensively metabolized
      in the liver by cytochrome P450 3A4 enzyme. Over a 10-day period, approximately
      86% of an orally administered radioactive dose is recovered in the feces, with
      <4% of the dose in the urine. After daily oral administration, steady-state
      plasma levels are reached in 10 days and are 2-fold higher than those achieved
      after single doses. Gefitinib effectiveness was demonstrated in a randomized,
      double-blind, Phase II, multicenter trial comparing two oral doses of gefitinib
      (250 versus 500 mg/day). A total of 216 patients were enrolled. The 142 patients
      who were refractory to or intolerant of a platinum and docetaxel comprised the
      evaluable population for the efficacy analysis. A partial tumor response occurred
      in 14% (9 of 66) of patients receiving 250 mg/day gefitinib and in 8% (6 of 76)
      of patients receiving 500 mg/day gefitinib. The overall objective response rate
      (RR) for both doses combined was 10.6% (15 of 142 patients; 95% confidence
      interval, 6.0-16.8%). Responses were more frequent in females and in nonsmokers.
      The median duration of response was 7.0 months (range, 4.6-18.6+ months). Other
      submitted data included the results of two large trials conducted in chemotherapy
      naive, stage III and IV non-small cell lung cancer patients. Patients were
      randomized to receive gefitinib (250 or 500 mg daily) or placebo, in combination
      with either gemcitabine plus cisplatin (n = 1093) or carboplatin plus paclitaxel
      (n = 1037). Results from this study showed no benefit (RR, time to progression,
      or survival) from adding gefitinib to chemotherapy. Consequently, gefinitib is
      only recommended for use as monotherapy. Common adverse events associated with
      gefitinib treatment included diarrhea, rash, acne, dry skin, nausea, and
      vomiting. Interstitial lung disease has been observed in patients receiving
      gefitinib. Worldwide, the incidence of interstitial lung disease was about 1% (2%
      in the Japanese post-marketing experience and about 0.3% in a United States
      expanded access program). Approximately one-third of the cases have been fatal.
      Gefitinib was approved under accelerated approval regulations on the basis of a
      surrogate end point, RR. No controlled gefitinib trials, to date, demonstrate a
      clinical benefit, such as improvement in disease-related symptoms or increased
      survival. Accelerated approval regulations require the sponsor to conduct
      additional studies to verify that gefitinib therapy produces such benefit.

PMID- 14977818
TI  - Safety and biological activity of repeated doses of recombinant human Flt3 ligand
      in patients with bone scan-negative hormone-refractory prostate cancer.
AB  - PURPOSE: The purpose of this study was to evaluate the safety, biological
      activity, and feasibility of repeated doses of the dendritic cell (DC)
      stimulating agent Flt3 ligand (FL) in patients with bone scan-negative hormone
      refractory prostate cancer. EXPERIMENTAL DESIGN: Thirty-one patients with hormone
      refractory prostate cancer who had elevated prostate-specific antigen (PSA)
      levels and negative bone scans were enrolled. Six cycles (28 days each) were
      planned. In the first cycle, patients were randomized to FL or placebo. All
      patients received open-label FL during the next five courses. DC, anti-FL
      antibody, and PSA levels were measured every 15 days to assess biological
      activity. RESULTS: DCs increased markedly in FL-treated patients from precycle to
      day 15, and the increase was consistent in each cycle. Mean percentages of DCs in
      peripheral blood ranged from 1.4% to 1.9% precycle and from 10.1% to 13.9% on day
      15, and after the first cycle, absolute counts on day 15 were approximately 29
      fold higher than precycle levels. Natural killer cell counts (CD56(+)) were found
      to be elevated after cycle 1 (154% increase versus 2.8% decrease in placebo group
      at day 22). Twenty-two of 27 patients tested developed nonneutralizing anti-FL
      antibody. The most frequently experienced toxicity was injection site reaction,
      followed by asthenia, rash, and diarrhea. Although median PSA levels did not vary
      during any cycle, a significant slowing in velocity of PSA was observed while
      patients were on-study (relative velocity = 0.002) compared with prestudy PSA
      velocity (relative velocity = 0.007). CONCLUSIONS: FL was well tolerated. FL
      consistently produced an increase in DC count without any evidence of decreasing
      response with continued exposure. The expansion of DCs and the slowing of PSA
      velocity after administration of FL suggest potential clinical applications in
      the immunotherapy of prostate cancer.

PMID- 14977819
TI  - Predicting radiosensitivity using DNA end-binding complex analysis.
AB  - Previous reports have suggested that measuring radiosensitivity of normal and
      tumor cells would have significant clinical relevance for the practice of
      radiation oncology. We hypothesized that radiosensitivity might be predicted by
      analyzing DNA end-binding complexes (DNA-EBCs), which form at DNA double-strand
      breaks, the most important cytotoxic lesion caused by radiation. To test this
      hypothesis, the DNA-EBC pattern of 21 primary human fibroblast cultures and 15
      tumor cell lines were studied. DNA-EBC patterns were determined using a modified
      electrophoretic mobility shift assay and were correlated with radiosensitivity,
      as measured by SF2. DNA-EBC analysis identified a rapidly migrating ATM
      containing band (identified as "band-A") of which the density correlated with SF2
      (0.02 </= SF2 </= 0.41) in primary fibroblasts (r(2) = 0.77). The DNA-EBC pattern
      of peripheral blood lymphocytes was identical to that of fibroblasts. In
      addition, band-A density correlated with SF2 (0.35 </= SF2 </= 0.80) in 15 human
      tumor cell lines (r(2) = 0.91). Densitometry of other bands, or total DNA-EBC
      binding, correlated more poorly with SF2 (r(2) < 0.45). These data indicate that
      DNA-EBC analysis may be a practical, clinically relevant predictor of tumor and
      primary cell radiosensitivity.

PMID- 14977820
TI  - Epithelial-cadherin and beta-catenin expression changes in pancreatic
      intraepithelial neoplasia.
AB  - PURPOSE: Cadherins and associated catenins are important mediators of epithelial
      cell-cell adhesion, as well as the Wnt-signaling pathway. Significant changes in
      their expression or structure have been implicated in malignancy. This study
      aimed to investigate the epithelial-cadherin (E-cadherin) and beta-catenin
      expression changes during multistage, pancreatic ductal carcinogenesis.
      EXPERIMENTAL DESIGN: Ninety-four Whipple resection specimens were retrieved from
      the surgical pathology files of the University Health Network (Toronto, Canada),
      from which tissue microarray blocks containing 36 pancreatic ductal
      adenocarcinomas, 34 PanIN-1A lesions, 28 PanIN-1B lesions, 27 PanIN-2 lesions, 16
      PanIN-3 lesions, and 32 normal ducts were constructed. The E-cadherin, beta
      catenin, and the phosphorylated glycogen synthase kinase-3beta of the Wnt/beta
      catenin pathway were immunohistochemically evaluated in these duct/PanIN lesions.
      RESULTS: There was marked increase in the cytoplasmic E-cadherin expression in
      PanIN lesions (P < 0.0001) and adenocarcinoma (P = 0.005) compared with normal
      pancreatic ducts. In contrast, reduced/loss of E-cadherin membranous expression
      was also significant in ductal adenocarcinoma compared with both the PanIN
      lesions (P < 0.0001) and normal ducts (P = 0.05). The beta-catenin expression
      showed significantly more frequent aberrant nuclear localization in high-grade
      PanIN lesions, particularly PanIN2 and in adenocarcinoma compared with normal
      ducts or low grade PanIN lesions (P < 0.0001). However, there was a lack of
      correlation between phospho(Ser9)-glycogen synthase kinase-3beta cytoplasmic
      expression and beta-catenin aberrant nuclear expression (P = 0.07). CONCLUSIONS:
      Aberration in the expression of E-cadherin and its associated beta-catenin is
      evident in pre-invasive (PanIN) neoplastic pancreatic duct cells, suggesting
      involvement of pathways leading to beta-catenin stabilization during pancreatic
      duct cell carcinogenesis.

PMID- 14977821
TI  - High-throughput analysis of genome-wide receptor tyrosine kinase expression in
      human cancers identifies potential novel drug targets.
AB  - Novel high-throughput analyses in molecular biology allow sensitive and rapid
      identification of disease-related genes and drug targets. We have used
      quantitative real-time reverse transcription-PCR reactions (n = 23000) to analyze
      expression of all human receptor tyrosine kinases (n = 56) in malignant tumors (n
      = 313) of different origins and normal control samples (n = 58). The different
      tumor types expressed very different numbers of receptor tyrosine kinases:
      whereas brain tumors and testicular cancer expressed 50 receptor tyrosine
      kinases, acute myeloid leukemia (AML) samples expressed only 20 different ones.
      Specimens of similar tumor origin exhibited characteristic receptor tyrosine
      kinase expression patterns and were grouped together in hierarchical cluster
      analyses. When we focused on specific tumor entities, receptor tyrosine kinases
      were identified that were disease and/or stage specific. Leukemic blasts from AML
      bone marrow samples differed significantly in receptor tyrosine kinase expression
      compared with normal bone marrow and purified CD34+ cells. Among the
      differentially expressed receptor tyrosine kinases, we found FLT3, c-kit, CSF1
      receptor, EPHB6, leukocyte tyrosine kinase, and ptk7 to be highly overexpressed
      in AML samples. Whereas expression changes of some of these were associated with
      altered differentiation patterns (e.g., CSF1 receptor), others, such as FLT3,
      were genuinely overexpressed in leukemic blasts. These data and the associated
      database (http://medweb.uni-muenster.de/institute/meda/research/) provide a
      comprehensive view of receptor tyrosine kinase expression in human cancer. This
      information can assist in the definition of novel drug targets.

PMID- 14977822
TI  - Pleomorphic characteristics of a germ-line KIT mutation in a large kindred with
      gastrointestinal stromal tumors, hyperpigmentation, and dysphagia.
AB  - PURPOSE: Somatic mutations that result in the activation of the growth factor
      receptor KIT are commonly found in gastrointestinal stromal tumors (GISTs). Six
      families have been reported in which a germ-line mutation in KIT is associated
      with an autosomal dominant predisposition to the development of GISTs.
      Hyperpigmentation, urticaria pigmentosa, and dysphagia have been described in
      some, but not all, families. Preliminary correlations between the site of
      mutation and the clinical phenotype have been proposed, but the strength of these
      associations is not defined. DESIGN: A large kindred with multiple GISTs,
      hyperpigmentation, and dysphagia was identified after the index case presented
      with multiple GISTs. A germ-line mutation in KIT (W557R) was identified in an
      affected cousin, after which a large family meeting was held and testing offered.
      Clinical data were obtained by interview and, whenever possible, medical record
      documentation. RESULTS: To date, 19 individuals have been tested, and the
      mutation has been shown to cosegregate with the syndrome. The phenotypic
      expression, however, is variable. GISTs, often presenting as upper
      gastrointestinal bleeding, and hyperpigmentation are common, but not diagnosed in
      all documented or obligate carriers. Dysphagia is a less prevalent complaint. The
      diagnosis of GISTs appears to be made at a younger age in more recent
      generations. Metastatic disease is uncommon. CONCLUSIONS: A germ-line mutation in
      KIT resulting in an amino acid substitution in the juxtamembrane region is
      associated with a syndrome of GIST, hyperpigmentation, and dysphagia, although
      the prominence of each component varies.

PMID- 14977823
TI  - Antiangiogenic therapy by local intracerebral microinfusion improves treatment
      efficiency and survival in an orthotopic human glioblastoma model.
AB  - Targeting active angiogenesis, which is a major hallmark of malignant gliomas, is
      a potential therapeutic approach. For effective inhibition of tumor-induced
      neovascularization, antiangiogenic compounds have to be delivered in sufficient
      quantities over a sustained period of time. The short biological half-life of
      many antiangiogenic inhibitors and the impaired intratumoral blood flow create
      logistical difficulties that make it necessary to optimize drug delivery for the
      treatment of malignant gliomas. In this study, we compared the effects of
      endostatin delivered by daily systemic administration or local intracerebral
      microinfusion on established intracranial U87 human glioblastoma xenografts in
      nude mice. Noninvasive magnetic resonance imaging methods were used to assess
      treatment effects and additional histopathological analysis of tumor volume,
      microvessel density, proliferation, and apoptosis rate were performed. Three
      weeks of local intracerebral microinfusion of endostatin (2 mg/kg/day) led to 74%
      (P < 0.05) reduction of tumor volumes with decreased microvessel densities
      (33.5%, P < 0.005) and a 3-fold increased tumor cell apoptosis (P < 0.002).
      Systemic administration of a 10-fold higher amount of endostatin (20 mg/kg/day)
      did not result in a reduction of tumor volume nor in an increase of tumor cell
      apoptosis despite a significant decrease of microvessel densities (26.9%, P <
      0.005). Magnetic resonance imaging was used to successfully demonstrate treatment
      effects. The local microinfusion of human endostatin significantly increased
      survival when administered at 2 mg/kg/day and was prolonged further when the dose
      was increased to 12 mg/kg/day. Our results indicate that the local intracerebral
      microinfusion of antiangiogenic compounds is an effective way to overcome the
      logistical problems of inhibiting glioma-induced angiogenesis.

PMID- 14977824
TI  - Radiosensitization by antisense anti-MDM2 mixed-backbone oligonucleotide in in
      vitro and in vivo human cancer models.
AB  - PURPOSE: The MDM2 oncogene, amplified or overexpressed in many human cancers, has
      been suggested to be a novel target for cancer therapy. We have demonstrated a
      second-generation antisense antihuman-MDM2 oligonucleotide to have antitumor
      activity when administered alone or in combination with cancer chemotherapeutic
      agents. In the present study, we investigated the effect of the antisense
      oligonucleotide on radiation therapy. EXPERIMENTAL DESIGN: The in vitro
      radiosensitization activity was determined in cell lines of human cancers of
      prostate (LNCaP and PC3), breast (MCF-7 and MDA-MB-468), pancreas (PANC-1), and
      glioma (U87-MG and A172) and its in vivo radiosensitization activity in xenograft
      models of LNCaP, PC3, MCF-7, MDA-MB-468, and PANC-1. RESULTS: In cells containing
      at least one functional p53 allele (LNCaP, U87-MG, and A172), after specific
      inhibition of MDM2 expression, p53 and p21 levels were elevated. In LNCaP cells,
      the Bax level was increased, and Bcl-2 and E2F1 levels were decreased. In PC3
      cells that are p53 null, after inhibition of MDM2 expression, Bax and p21 levels
      were elevated, and E2F1 levels were decreased. On the basis of in vitro
      clonogenic assay, the antisense oligonucleotide, in a sequence-specific manner,
      significantly increased radiation-induced antiproliferation effects. It also
      increased radiation-induced inhibitory effects on tumor growth in SCID or nude
      mice bearing LNCaP, PC3, MCF-7, MDA-MB-468, and PANC-1 xenografts. CONCLUSIONS:
      These results suggest that MDM2 has a role in radiation therapy of human cancers,
      regardless of p53 status, providing a basis for future development of MDM2
      inhibitors, such as antisense oligonucleotides, as radiosensitizers.

PMID- 14977825
TI  - The evaluation of recombinant, chimeric, tetravalent antihuman CD22 antibodies.
AB  - PURPOSE: The purpose of this study was to prepare chimeric antihuman CD22
      tetravalent monoclonal antibodies (MAbs) with high functional affinity, long
      persistence in the circulation, increased antitumor activity, and conserved
      effector function in vitro. EXPERIMENTAL DESIGN: We investigated the
      association/dissociation rates of these tetravalent antibodies using CD22(+)
      Daudi lymphoma cells. We then tested their ability to interact with Fc receptors
      on a human cell line (U937), to mediate antibody-dependent cellular cytotoxicity
      with human natural killer cells, to bind human C1q, to inhibit the in vitro
      growth of CD22 Daudi cells, and to persist in the circulation. RESULTS: The rate
      of dissociation of the tetravalent MAbs versus the divalent antibody was
      considerably slower. These tetravalent MAbs inhibited the in vitro proliferation
      of CD22 Daudi cells at a concentration that was at least 100-fold lower than that
      of the divalent murine antibody. The tetravalent MAbs containing both the CH2 and
      CH3 domains and a chimeric recombinant divalent antibody bound similarly to Fc
      receptor, C1q, and mediate antibody-dependent cellular cytotoxicity equally well
      with human natural killer cells. The persistence in the circulation of chimeric
      tetravalent MAbs was considerably longer than that of chemical homodimers.
      CONCLUSIONS: The tetravalent anti-CD22 MAbs with intact Fc regions should make
      effective therapeutic agents for B-cell tumors.

PMID- 14977826
TI  - Phase I and pharmacokinetic study of the cytotoxic ether lipid ilmofosine
      administered by weekly two-hour infusion in patients with advanced solid tumors.
AB  - PURPOSE: A Phase I trial was performed to determine the dose-limiting toxicity
      and maximum tolerated dose, and to describe the pharmacokinetics of the alkyl
      lysophospholipid, ilmofosine, when administered as a weekly 2-h infusion in
      patients with solid tumors. EXPERIMENTAL DESIGN: Thirty-nine patients were
      entered into a trial of ilmofosine administered weekly for 4 weeks followed by a
      2-week rest period. Dose escalation occurred in 10 levels from 12 to 650 mg/m(2).
      RESULTS: Thirty-six patients were evaluable for toxicity. The median number of
      cycles per patient was 1 (range, 1-4). Dose-limiting gastrointestinal toxicity
      occurred at 650 mg/m(2) with grade 3 nausea in two patients and grade 3 vomiting
      and diarrhea in one patient. Grade 2 diarrhea was observed in four of six
      patients treated at 550 mg/m(2). In addition, two patients treated at 550 mg/m(2)
      and two patients treated at 650 mg/m(2) experienced a decline in performance
      status of two or more levels that was determined to be due to treatment. There
      were no tumor responses. Stabilization of disease for at least 8 weeks occurred
      in six patients. Plasma concentrations of ilmofosine and its sulfoxide metabolite
      were evaluated by high-pressure liquid chromatography. The elimination of both
      compounds was biexponential with terminal half-lives of approximately 40 h for
      ilmofosine and 48 h for the sulfoxide. The area under the concentration-time
      curve was dose-proportional for each compound, and there was no evidence of
      saturable kinetics. CONCLUSIONS: The dose-limiting toxicity of ilmofosine is
      gastrointestinal and the recommended dose for Phase II trials is 450 mg/m(2) as a
      2-h weekly infusion. The relatively long half-life of ilmofosine and its active
      metabolite support the use of this intermittent schedule.

PMID- 14977827
TI  - Phase I clinical and pharmacokinetic study of BMS-247550, a novel derivative of
      epothilone B, in solid tumors.
AB  - PURPOSE: The purpose of this study was to determine the maximum tolerated dose,
      toxicity, and pharmacokinetics of BMS-247550 administered as a 1-h i.v. infusion
      every 3 weeks. EXPERIMENTAL DESIGN: Patients with advanced solid malignancies
      were premedicated and treated with escalating doses of BMS-247550. Blood sampling
      was performed to characterize the pharmacodynamics and pharmacokinetics of BMS
      247550. RESULTS: Twenty-five patients were treated at six dose levels ranging
      from 7.4 to 59.2 mg/m(2). At 50 mg/m(2), 4 of 9 patients (44.4%) had dose
      limiting toxicity (neutropenia, abdominal pain/nausea). At 40 mg/m(2) (the
      recommended Phase II dose), 2 of 12 patients (16.7%) had dose-limiting
      neutropenia. Overall, the most common nonhematological toxicity was
      fatigue/generalized weakness (grade 3-4 seen in 9.0% of patients), followed by
      neurosensory deficits manifested as peripheral neuropathy and by gastrointestinal
      discomfort. At 40 mg/m(2), the incidence of grade 3 fatigue, abdominal pain,
      diarrhea, and neuropathy was 7.7%. Grade 1-2 neuropathy was observed in all
      patients enrolled and treated at 40 mg/m(2). Two patients with paclitaxel
      refractory ovarian cancer, one patient with taxane-naive breast cancer, and
      another patient with docetaxel-refractory breast cancer had objective partial
      responses (lasting 6.0, 5.3, 3.0, and 4.5 months, respectively). The mean
      pharmacokinetic parameter values during course 1 for clearance, volume of
      distribution, and apparent terminal elimination half-life at the 40 mg/m(2)
      (recommended Phase II dose) dose level were 21 liters/h/m(2), 826 liters/m(2),
      and 35 h (excluding one outlier of 516 h), respectively. Values during course 1
      and course 2 were similar. CONCLUSIONS: The recommended dose for Phase II
      evaluation of BMS-247550 is 40 mg/m(2), although more long-term observations are
      needed. BMS-247550 has advantages over taxanes in relation to drug resistance and
      warrants further study.

PMID- 14977828
TI  - Clinical efficacy, tolerability, and safety of SAM486A, a novel polyamine
      biosynthesis inhibitor, in patients with relapsed or refractory non-Hodgkin's
      lymphoma: results from a phase II multicenter study.
AB  - PURPOSE: SAM486A is a new inhibitor of S-adenosyl-methionine-decarboxylase, a key
      enzyme for polyamine biosynthesis. It is more potent than the first generation S
      adenosyl-methionine-decarboxylase inhibitor methylglyoxal bis-guanylhydrazone.
      This Phase IIa study reports the findings of SAM486A monotherapy in patients with
      refractory or relapsed non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Forty
      one previously treated patients with either diffuse large cell, follicular, or
      peripheral T-cell NHL were treated i.v. with 100 mg/m(2) SAM486A as a daily 1-h
      infusion for 5 days repeated every 3 weeks. Treatment was continued for a total
      of eight cycles or until disease progression. RESULTS: Two patients, both with
      large B-cell lymphoma, showed a complete response at cycle 3 that was maintained
      for >or=13 and >or=28 months. Five patients had a partial response, and 3 had
      stable disease at last follow-up. The overall response rate (complete response
      plus partial response) was 18.9% for evaluable patients (7 patients). Anemia was
      the primary hematological toxicity and observed in 7 (17.1%) patients. Five
      patients experienced grade 3/4 anemia. Four patients (9.8%) experienced grade 3/4
      febrile neutropenia and grade 3/4 thrombocytopenia, respectively.
      Nonhematological toxicities were mild to moderate in intensity. The most frequent
      side effects were nausea (39%), vomiting (22%), diarrhea (19.5%), asthenia
      (17.1%), abdominal pain (14.6%), and flushing (9.8%). CONCLUSION: SAM486A has a
      promising clinical activity in patients with poor prognosis NHL and manageable
      safety profile. To further define the role of SAM486A, in the treatment of NHL,
      additional studies are warranted.

PMID- 14977829
TI  - Phase I study of weekly mitoxantrone and docetaxel before prostatectomy in
      patients with high-risk localized prostate cancer.
AB  - PURPOSE: The purpose is to determine the dose-limiting toxicity (DLT) and maximum
      tolerated dose (MTD) of mitoxantrone and docetaxel administered weekly before
      prostatectomy in men with localized prostate cancer at high risk for recurrence.
      EXPERIMENTAL DESIGN: Twenty-two patients were treated with four cycles of
      docetaxel 35 mg/m(2) and increasing doses of mitoxantrone starting at 2 mg/m(2)
      repeated weekly for 3 weeks of a 4-week cycle before prostatectomy. The MTD was
      defined as that dose at which fewer than one-third of patients experienced a DLT
      (>or=grade 4 hematological or >or=>grade 3 nonhematological toxicity). Changes in
      serum prostate-specific antigen and serum testosterone, and pathological outcome
      with surgery were secondary endpoints. RESULTS: The MTD for mitoxantrone in
      combination with this dose of docetaxel was 4 mg/m(2). Neutropenia was the DLT
      for the combination. Ten of 12 patients treated at the MTD completed the planned
      16 weeks of chemotherapy, whereas 2 discontinued therapy early because of
      toxicity. The median reduction in PSA was 41% (range, 4-88%). Serum testosterone
      levels remained constant postchemotherapy. CONCLUSIONS: In this patient
      population, the planned Phase II regimen is 4 mg/m(2) mitoxantrone and 35 mg/m(2)
      docetaxel weekly for 3 of every 4 weeks. Delivery of this regimen before
      prostatectomy is feasible with acceptable toxicity. Additional studies are needed
      to determine whether this combined modality approach will reduce cancer
      recurrence rates in this high-risk population. Because extent of disease and
      exposure to prior therapy may impact treatment tolerance these safety data may
      not be applicable to patients with advanced prostate cancer.

PMID- 14977830
TI  - Genetic and plasma markers of venous thromboembolism in patients with high grade
      glioma.
AB  - PURPOSE: Deep venous thrombosis/pulmonary embolism (DVT/PE) is a frequent
      complication in the course of cancer, particularly in brain tumors. We
      investigated genetic and plasma factors possibly associated with risk of DVT/PE
      in patients with high-grade glioma. EXPERIMENTAL DESIGN: In a case-control study,
      we studied polymorphisms of the genes coding for factor II (G20210A), factor V
      (G1691A), methylenetetrahydrofolate-reductase (C677T), tissue-type plasminogen
      activator (tPA; insertion/deletion), plasminogen activator inhibitor-1 (PAI-1;
      4G/5G), and vascular endothelial growth factor (VEGF; C936T). We also measured
      plasma levels of D-dimer, lipoprotein (lp) (a), homocysteine, VEGF, tPA, and PAI
      1, comparing healthy control patients with patients with glioma or with patients
      with neurological nonneoplastic disease (multiple sclerosis). RESULTS: Genotype
      frequencies of polymorphisms analyzed were similar in patients with glioma and in
      healthy matched population. D-dimer, lp (a), homocysteine, VEGF, tPA, and PAI-1
      plasma levels were significantly higher in patients with glioma than in healthy
      controls, whereas patients having neurological nonneoplastic disease had plasma
      values of these molecules not significantly different from healthy controls.
      VEGF, tPA, and PAI-1 were also found at high-plasma levels in patients carrying
      genotypes that, in healthy controls, were associated with "low-producing"
      phenotypes. CONCLUSIONS: Genetic risk factors alone did not explain the high
      incidence of DVT/PE observed in patients with glioma. Higher plasma levels of
      molecules influencing the coagulation pathways indicate that the tumor itself
      might confer an increased risk of DVT/PE; thus, D-dimer, homocysteine, lp (a),
      VEGF, tPA, and PAI-1 look like good candidates to be evaluated as DVT/PE
      prognostic factors.

PMID- 14977831
TI  - Ribonucleotide reductase messenger RNA expression and survival in
      gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients.
AB  - PURPOSE: No chemotherapy regimen, including the widely used combination of
      gemcitabine/cisplatin, confers significantly improved survival over any other in
      metastatic non-small cell lung cancer (NSCLC); however, the selection of patients
      according to key genetic characteristics can help to tailor chemotherapy.
      Ribonucleotide reductase subunit M1 (RRM1) is involved in DNA synthesis and
      repair and in gemcitabine metabolism, and the excision repair cross-complementing
      group 1 (ERCC1) gene has been related to cisplatin activity. EXPERIMENTAL DESIGN:
      Patients were part of a large randomized trial carried out from September 1998 to
      July 2000, comparing gemcitabine/cisplatin versus
      gemcitabine/cisplatin/vinorelbine versus gemcitabine/vinorelbine followed by
      vinorelbine/ifosfamide. We analyzed RRM1 and ERCC1 mRNA expression in paraffin
      embedded samples obtained from bronchoscopy by real-time quantitative reverse
      transcription-PCR. Results were correlated with survival using the Kaplan-Meier
      method. RESULTS: A total of 100 patients were assessed. There was a strong
      correlation between RRM1 and ERCC1 mRNA expression levels (Spearman r = 0.410; P
      < 0.001). In the gemcitabine/cisplatin arm, patients with low RRM1 mRNA
      expression levels had significantly longer median survival than those with high
      levels [13.7 versus 3.6 months; 95% confidence interval (CI), 9.6-17.8 months; P
      = 0.009]. Median survival was also significantly longer among patients with low
      mRNA expression levels of both RRM1 and ERCC1 (not reached), than among those
      with high levels of both genes (6.8 months; 95% CI, 2.6-11.1 months; P = 0.016).
      CONCLUSIONS: RRM1 mRNA expression is a crucial predictive marker of survival in
      gemcitabine/cisplatin-treated patients. Genetic testing of RRM1 mRNA expression
      levels can and should be used to personalize chemotherapy.

PMID- 14977832
TI  - Heterogeneous patterns of FLT3 Asp(835) mutations in relapsed de novo acute
      myeloid leukemia: a comparative analysis of 120 paired diagnostic and relapse
      bone marrow samples.
AB  - PURPOSE: We analyzed Asp(835) mutations of FLT3 on paired marrow samples at
      diagnosis and relapse from 120 adult patients with de novo acute myeloid leukemia
      (AML) to determine the role of FLT3 Asp(835) mutation in the relapse of AML.
      EXPERIMENTAL DESIGN: Asp(835) mutation was analyzed by DNA PCR amplification of
      exon 20 of FLT3 gene followed by EcoRV digestion. All of the mutations were
      confirmed by sequence analysis. Mutant to wild-type allelic ratio was determined
      by Genescan analysis. The Expand Long Template PCR System was used to determine
      the allelic location of internal tandem duplication of FLT3 (FLT3/ITD) and
      Asp(835) mutations. RESULTS: Thirteen patients had Asp(835) mutations at
      diagnosis, of them 8 lost the mutations at relapse, and the remaining 5 patients
      carrying Asp(835) mutations at diagnosis relapsed with the identical mutation
      types. Another 6 patients acquired Asp(835) mutations at relapse. Five samples
      harbored both FLT3/ITD and Asp(835) mutations that were found on different
      alleles by cloning analysis in the 3 patients studied. There were no differences
      in WBC count, French-American-British subtype, percentage of marrow blasts, or
      circulating blasts between patients with and without Asp(835) mutations, whereas
      the difference in the prevalence of Asp(835) mutations among
      cytogenetic/molecular subgroups was statistically significant (P = 0.025).
      CONCLUSIONS: The present study showed that patients with AML had heterogeneous
      patterns of FLT3 Asp(835) mutations, either acquisition or loss of the mutations
      at relapse. Asp(835) mutant clone may develop as a secondary event in a subset of
      patients with AML.

PMID- 14977833
TI  - PC cell-derived growth factor expression in prostatic intraepithelial neoplasia
      and prostatic adenocarcinoma.
AB  - PURPOSE: PCDGF (PC cell-derived growth factor), also called progranulin, is a
      M(r) 88000 glycoprotein precursor of granulin. It is a novel growth factor that
      stimulates cell proliferation, confers epithelial tumorigenesis, and promotes
      tumor invasion. Here we investigate the potential of PCDGF as a therapeutic
      target for prostate cancer. EXPERIMENTAL DESIGN: We studied the expression of
      PCDGF in invasive prostate cancer, adjacent high-grade prostatic intraepithelial
      neoplasia (PIN), and benign prostate tissue from 99 human prostate specimens. The
      level of PCDGF expression was correlated with various clinicopathological
      characteristics. RESULTS: Normal prostate tissue did not express (53/99), or
      expressed low levels (46/99) of PCDGF. In the 46 normal prostate specimens that
      expressed PCDGF, most of them had less than 10% of cells expressing PCDGF. PCDGF
      expression could be detected in more than 50% of cells in all specimens of PIN
      and invasive prostate cancer. The expression of PCDGF in normal prostate tissue
      was much less intense and in a smaller fraction of cells than in PIN and invasive
      adenocarcinoma (P < 0.0001). There was no correlation of PCDGF expression with
      age, Gleason score, pathological stage, status of lymph node metastasis,
      extraprostatic extension, perineural invasion, surgical margins, and vascular
      invasion. CONCLUSIONS: Our data suggest that the induction of PCDGF expression
      occurs during the development of PIN. PCDGF may be a new molecular target for the
      treatment and prevention of prostate cancer.

PMID- 14977834
TI  - Down regulation of high in normal-1 (HIN-1) is a frequent event in stage I non
      small cell lung cancer and correlates with poor clinical outcome.
AB  - PURPOSE: The aim of this study was to evaluate the prevalence and the clinical
      significance of HIN-1 mRNA expression in early stage non-small cell lung
      carcinomas (NSCLCs). EXPERIMENTAL DESIGN: A series of 91 NSCLC patients with
      stage I neoplastic disease was studied. HIN-1 expression was investigated by
      quantitative real-time reverse transcription-PCR on tumor specimens and matching
      normal lung tissues. Variables were analyzed by chi(2) test and Fisher's exact
      tests. Survival was evaluated with the method of Kaplan-Meier. Multivariate
      analysis was performed with Cox's proportional hazards model. RESULTS: Seventy
      one (78%) tumors showed a reduction of HIN-1 mRNA compared with the normal
      counterpart. The range of reduction varied greatly, from -2-fold to -3350-fold.
      Setting a cutoff at -46-fold (median value of HIN-1 mRNA reduction), 46 cases
      (51%) had a markedly reduced expression, and 45 cases (49%) showed a normal or
      slightly reduced expression. A statistically significant association between low
      HIN-1 mRNA levels and T status was observed (P = 0.036). Univariate survival
      curves, estimated using the method of Kaplan-Meier, defined a significant
      association between HIN-1 expression and both overall survival (P = 0.0095) and
      disease-free survival (P = 0.0122). A multivariate analysis, performed by Cox's
      proportional hazards regression model, confirmed that a low HIN-1 expression was
      the only significant factor to predict poor prognosis. CONCLUSIONS: Our data
      indicate that HIN-1 expression, measured by real-time reverse transcription-PCR,
      is a possible prognostic factor in patients with stage I NSCLC. Additional
      studies are required to further validate this potential prognostic marker.

PMID- 14977835
TI  - Vascular endothelial growth factor expression is up-regulated by EWS-ETS
      oncoproteins and Sp1 and may represent an independent predictor of survival in
      Ewing's sarcoma.
AB  - PURPOSE: Tumor markers ideally allow monitoring and prediction of disease
      progression. In Ewing's sarcoma, a devastating childhood cancer, only a few
      reliable prognostic markers have been identified. To this end, we analyzed the
      expression of four tumor-promoting proteins, cyclin D1, HER2/Neu, Mdm2, and
      vascular endothelial growth factor (VEGF), in Ewing's sarcoma. EXPERIMENTAL
      DESIGN AND RESULTS: Thirty-one tissue samples from patients with Ewing's sarcoma
      were stained with antibodies against cyclin D1, HER2/Neu, Mdm2, or VEGF. Whereas
      no significant expression of HER2/Neu and Mdm2 was detected, positive cyclin D1
      and VEGF staining was observed in 42% and 55% of all tumors, respectively.
      Importantly, VEGF expression was found to be an independent negative predictor of
      survival in Ewing's sarcoma patients, whereas cyclin D1 expression did not
      correlate with survival in these patients. Consistently, the Ewing's sarcoma
      specific EWS-ETS oncoproteins were capable of activating both the cyclin D1 and
      VEGF promoters in transient transfections of tissue culture cells. Furthermore,
      this activation was enhanced by coexpression of the Sp1 transcription factor.
      Using a mammalian two-hybrid system, some evidence was obtained that this may
      involve a physical interaction between EWS-ETS and Sp1 proteins. CONCLUSIONS: Our
      data reveal that VEGF may serve as a prognostic marker in Ewing's sarcoma
      patients and provide a molecular mechanism by which VEGF and cyclin D1 expression
      is up-regulated in approximately half of all Ewing's sarcomas.

PMID- 14977836
TI  - Phospho-serine-118 estrogen receptor-alpha detection in human breast tumors in
      vivo.
AB  - PURPOSE: To determine whether estrogen receptor (ER)-alpha specifically
      phosphorylated at Ser(118) is detectable in multiple human breast cancer biopsy
      samples. To gain insight into possible roles for P-Ser(118)-ERalpha in human
      breast cancer in vivo. EXPERIMENTAL DESIGN: A specific antibody for P-Ser(118)
      ERalpha was validated for immunohistochemistry (IHC), and Western blot analysis
      confirmed IHC results. IHC was used to determine the relationship of P-Ser(118)
      ERalpha to known prognostic markers and active mitogen-activated protein kinase
      (MAPK; erk1/2) expression. RESULTS: P-Ser(118)-ERalpha was significantly
      correlated with the expression of total ER, determined by ligand binding assay (r
      = 0.442, P = 0.002), but not with progesterone receptor expression or nodal
      status. P-Ser(118)-ERalpha was inversely correlated with histological grade (r = 
      0.34, P = 0.023), reflecting a similar trend for total ER (r = -0.287, P =
      0.056). Categorical contingency analysis confirmed that P-Ser(118)-ERalpha was
      more frequently associated with lower than higher grade breast tumors (P =
      0.038). In addition P-Ser(118)-ERalpha was significantly associated with
      detection of active MAPK (Erk1/2; Spearman r = 0.649, P < 0.0001; Fisher's exact
      test, P = 0.0004). CONCLUSIONS: P-Ser(118)-ERalpha detection is associated with a
      more differentiated phenotype and other markers of good prognosis in human breast
      cancer. P-Ser(118)-ERalpha is correlated with active MAPK in human breast tumor
      biopsies, suggesting the possibility that active MAPK either directly or
      indirectly has a role in the regulation of P-Ser(118)-ERalpha expression in vivo.
      These data provide evidence for a role of P-Ser(118)-ERalpha in human breast
      cancer in vivo.

PMID- 14977837
TI  - Altered expression of FAS system is related to adverse clinical outcome in stage
      I-II breast cancer patients treated with adjuvant anthracycline-based
      chemotherapy.
AB  - PURPOSE: To determine the prognostic value of Fas receptor and Fas ligand (FasL)
      as apoptosis-related biomarkers in the context of chemoresponsiveness in breast
      cancer (BC) patients submitted to anthracycline-based adjuvant therapy.
      EXPERIMENTAL DESIGN: Fas and FasL were investigated by immunohistochemistry in
      surgical samples collected from 167 stage I-IIa-b BC patients enrolled in a
      prospective clinical trial using epirubicin plus cyclophosphamide in the adjuvant
      setting. RESULTS: Fas and FasL were significantly associated with tumor stage (P
      < 0.0001). Multivariate analysis indicated that stage, loss of Fas (relative
      risk, 8.5 and 9.12; P < 0.0001) and FasL up-regulation (relative risk, 2.38 and
      2.88; P = 0.01) were independent prognostic variables influencing both disease
      free survival (DFS) and overall survival (OS). A Cox analysis using a four
      category Fas/FasL phenotype (+/-, +/+, -/+, -/-) as a stratification factor
      evidenced a highly positive association between Fas/FasL phenotype and the
      cumulative hazard of relapse and death in the entire series of patients. We also
      estimated the DFS and OS for different combinations of the pathological-tumor
      node-metastasis (TNM) stage and Fas/FasL by using the K sample log-rank exact
      test demonstrating that significantly shorter DFS and OS were observed in Fas
      negative and FasL-positive patients in both stage I-IIa and IIb. CONCLUSIONS:
      Data presented herein demonstrated that, according to a number of in vitro
      studies, the prognosis for BC patients receiving adjuvant anthracycline-based
      chemotherapy strongly depends on the Fas/FasL status. Therefore, a concomitant
      altered pattern of Fas/FasL expression seems to configure an aggressive tumor
      phenotype linked to disease progression.

PMID- 14977838
TI  - Synchronous coexpression of epidermal growth factor receptor and cyclooxygenase-2
      in carcinomas of the uterine cervix: a potential predictor of poor survival.
AB  - PURPOSE: To evaluate the potential of the new prognostic information gained by
      analyzing the coexpression of epidermal growth factor receptor (EGFR) and
      cyclooxygenase-2 (COX-2) in cervical cancer patients. EXPERIMENTAL DESIGN: Sixty
      eight patients with International Federation of Gynecology and Obstetrics stage
      IIB squamous cell carcinoma of the uterine cervix, who underwent concurrent
      chemoradiotherapy between 1993 and 1996, were divided into the following four
      groups according to their immunoreactivities for EGFR and COX-2 in paraffin
      embedded sections: (a). the EGFR-negative/COX-2-negative group (n = 11); (b). the
      EGFR-negative/COX-2-positive group (n = 8); (c). the EGFR-positive/COX-2-negative
      group (n = 27); and (d). the EGFR-positive/COX-2-positive group (n = 22). The
      clinical features, patterns of treatment failure, and survival data in the four
      groups were compared. RESULTS: Positive immunoreactivity for EGFR and COX-2 was
      observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong
      correlation was found between the levels of EGFR and COX-2 immunopositivity (R(2)
      = 0.05, P = 0.07). Patients in the EGFR-positive/COX-2-positive group had a
      higher likelihood of locoregional recurrence than those in the other three groups
      (P = 0.02). Of the patients in the four groups, patients positive for both
      oncoproteins were found to have the worst prognosis with an overall 5-year
      disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2
      negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for
      the EGFR-positive/COX-2-negative patients (P = 0.05, log-rank test). In addition,
      the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be
      an independent prognostic factor by univariate and multivariate analyses
      (relative risk = 4.0, P = 0.03). CONCLUSIONS: Given these observations, we
      conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as
      a potent molecular risk factor for predicting the poor survival of patients with
      the International Federation of Gynecology and Obstetrics stage IIB squamous cell
      carcinoma of the uterine cervix.

PMID- 14977839
TI  - Plasminogen activator inhibitor-1 as a potential marker for the malignancy of
      esophageal squamous cell carcinoma.
AB  - PURPOSE AND EXPERIMENTAL DESIGN: To test whether plasminogen activator inhibitor
      1 (PAI-1) can serve as a candidate marker for the malignancy of esophageal
      squamous cell carcinoma (SCC), we performed a quantitative reverse transcription
      PCR for PAI-1 gene and evaluated the possible relationship between PAI-1 gene
      expression levels and clinicopathological findings in esophageal SCC. RESULTS:
      Significant increases in PAI-1 scores were observed in metastasis-positive
      esophageal SCCs (3.08 +/- 0.80) compared with metastasis-negative ones (-0.31 +/-
      0.62; P = 0.0042). PAI-1 expression scores significantly increased with tumor
      stage (P = 0.05, ANOVA). CONCLUSIONS: These results suggested that PAI-1 might
      serve as a new parameter for prediction of prognosis in esophageal SCC.

PMID- 14977840
TI  - Clinical significance of the loss of KiSS-1 and orphan G-protein-coupled receptor
      (hOT7T175) gene expression in esophageal squamous cell carcinoma.
AB  - PURPOSE: Lymph node metastasis is the most important predictor of prognosis in
      esophageal squamous cell carcinoma (ESCC). Recently, KiSS-1 was cloned as a human
      metastasis suppressor gene, and an orphan G-protein-coupled receptor (hOT7T175)
      was identified as the endogenous receptor of the KiSS-1 product. However, the
      clinical importance of KiSS-1 and hOT7T175 gene expression in ESCC remains
      unclear. EXPERIMENTAL DESIGN: In this study, total RNA was extracted from tumors
      and noncancerous epithelia of 71 patients with ESCC who underwent surgical
      esophageal resection. The expression levels of KiSS-1, hOT7T175, and
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNAs were analyzed
      quantitatively by real-time reverse transcription-PCR and compared with the
      clinical findings. RESULTS: The mean KiSS-1:GAPDH and hOT7T175:GAPDH ratios of
      the tumors were 1.2 and 0.3 and were at the same levels as those in the
      noncancerous epithelia. The loss of KiSS-1 and hOT7T175 gene expression was
      detected in 38% and 61% of tumors. Loss of KiSS-1 and/or hOT7T175 gene expression
      was not correlated with tumor size or degree of tumor invasion but was found to
      be a significant predictor of lymph node metastasis. CONCLUSIONS: Loss of KiSS-1
      or hOT7T175 gene expression may be an important biomarker for detection of lymph
      node metastasis in ESCC.

PMID- 14977841
TI  - Functional characterization of the bladder cancer marker, BLCA-4.
AB  - INTRODUCTION: Bladder cancer is a common disease of the genitourinary tract for
      which the development of a noninvasive detection technique would have a
      significant impact on disease management. One of our previously identified
      bladder cancer-specific proteins, BLCA-4, appears to be associated with a "field
      effect" of the disease, and in clinical trials is able to separate individuals
      with bladder cancer from those without the disease with high sensitivity and
      specificity. The potential clinical utility of this marker has led to the
      analysis of its function in bladder cancer pathobiology. EXPERIMENTAL DESIGN: To
      additionally analyze the specificity of this marker, the expression in the urine
      of a variety of benign urologic conditions was analyzed. After cloning the gene
      encoding BLCA-4, functional aspects of the protein were analyzed by
      overexpressing it in cell systems, as well as its interaction with other
      transcription factors and in gel mobility shift assays. Finally, to determine the
      timing of expression in relation to the observance of bladder cancer, an animal
      model of the disease was examined. RESULTS: Expression of BLCA-4, the cDNA of
      which reveals that it is a novel member of the ETS transcription factor family,
      is not found in benign urologic conditions. Overexpression leads to increased
      growth rates of cells, and the protein interacts with other transcription
      factors. In vivo studies reveal that BLCA-4 expression occurs significantly
      before the observance of grossly visible tumors in an animal model of the
      disease. CONCLUSIONS: BLCA-4 is a bladder cancer marker that is highly specific
      and occurs early in the development of the disease. It appears to be a
      transcription factor that may play a role in the regulation of the gene
      expression in bladder cancer. BLCA-4 is a marker with significant clinical
      utility that may have an active role in the disease.

PMID- 14977842
TI  - Clinical significance of immunocytochemical detection of tumor cells using
      digital microscopy in peripheral blood and bone marrow of breast cancer patients.
AB  - PURPOSE: The presence of tumor cells in bone marrow has been reported to
      represent an important prognostic indicator in breast cancer, but the clinical
      significance of circulating cells in peripheral blood is less well known. The aim
      of this study was to evaluate the feasibility of identifying cytokeratin (CK)
      expressing cells in peripheral blood with an automat-assisted immunohistochemical
      detection system and to compare it with detection of tumor cells in bone marrow
      samples. EXPERIMENTAL DESIGN: Cytospun Ficoll fractions of peripheral blood and
      bone marrow were obtained simultaneously in 114 breast cancer patients at
      different stages of the disease (I to IV) before treatment with chemotherapy. The
      pancytokeratin (CK) monoclonal antibody A45-B/B3 (anti-CKs 8, 18, and 19) was
      used for epithelial cell detection. Immunostained cells were detected by an
      automated cellular imaging system (ChromaVision Medical System). RESULTS: CK+
      cells were detected in 28 (24.5%) patients in blood and in 67 (59%) patients in
      bone marrow. Twenty-six (93%) patients with CK-positive cells in blood also had
      positive bone marrow (P < 0.001). Positive cells were detected in peripheral
      blood in 3/39 (7.5%) operable breast cancers (stage I/II), 9 of 36 (25%) locally
      advanced breast cancers (stage III), and 16 of 39 (41%) patients with metastatic
      disease (stage IV; P = 0.017). In the subgroup of nonmetastatic patients (n =
      75), prognostic factors for poor disease-free survival were: absence of estrogen
      receptor; presence of CK+ cells in bone marrow (P = 0.012); clinical nodal
      involvement; large tumor size (T4); and presence of tumor emboli. Presence of
      circulating CK+ cells in the peripheral blood was not statistically correlated
      with disease-free survival. On multivariate analysis, independent indicators for
      disease-free survival were: absence of estrogen receptor (P = 0.043) and presence
      of CK+ cells in bone marrow (P = 0.076). CONCLUSIONS: The clinical relevance of
      circulating epithelial cells as a prognostic factor is not supported by the
      present data, especially in comparison with tumor cells in the bone marrow.
      However, this method of detection may be useful to monitor the efficacy of
      treatment in advanced or metastatic breast cancer.

PMID- 14977843
TI  - Prognostic and diagnostic significance of beta-catenin nuclear immunostaining in
      colorectal cancer.
AB  - In the present study, we investigated the prognostic and diagnostic significance
      of beta-catenin nuclear immunostaining in 60 specimens of normal colorectal
      tissue; 180 specimens of colorectal polyps, adenomas, and carcinomas; and 40
      specimens from patients with the simultaneous occurrence of polyps, adenomas, and
      carcinomas. Additional specimens from 59 patients with colorectal carcinoma and
      14 patients with adenoma who subsequently developed carcinoma were examined for
      possible survival study. Immunohistochemical staining showed that the occurrence
      of nuclear beta-catenin correlated with the sequential stages in colorectal
      carcinogenesis, in which positive staining was observed in 0% of normal tissues,
      8% of polyps, 92% of adenomas, and 100% of carcinomas. High immunohistochemical
      scores in colorectal carcinoma were significantly associated with lymph node
      metastasis and poor survival. Adenomas associated with synchronous or
      metachronous carcinomas showed significantly higher levels of nuclear beta
      catenin compared with adenomas without associated carcinomas. Nuclear
      translocation of beta-catenin was rare or absent in other types of cytokeratin 20
      positive adenocarcinomas examined (99 cases). Thus, it was positive in only 7% of
      colonic mucinous adenocarcinomas, 3% of pancreatic adenocarcinomas, 8% of ovarian
      mucinous cystadenocarcinomas, and 0% of gastric adenocarcinomas. However, 100% of
      primary and metastatic colorectal adenocarcinomas were positive for nuclear
      staining for beta-catenin. Thus, nuclear staining for beta-catenin may serve as
      an additional parameter to help distinguish colorectal adenocarcinomas from
      adenocarcinomas of other tissue sites. Collectively, the present large-scale
      study has clearly addressed the clinical significance of beta-catenin nuclear
      translocation with respect to tumor progression, survival, and differential
      diagnosis.

PMID- 14977844
TI  - Synergistic interactions between tamoxifen and trastuzumab (Herceptin).
AB  - PURPOSE: HER-2/neu and estrogen receptor (ER) are critical in the biology of
      breast carcinoma, and both are validated therapeutic targets. Extensive
      interactions between the signaling pathways of these receptors have been
      demonstrated. This suggests that targeting both receptors simultaneously may have
      a dramatic effect on the biology of breast cancer. This hypothesis was tested in
      cell culture experiments. EXPERIMENTAL DESIGN: ER-positive, HER-2/neu
      overexpressing BT-474 human breast carcinoma cells were cultured in the presence
      of the anti-HER-2/neu therapeutic antibody trastuzumab (Herceptin), the
      antiestrogen tamoxifen, or both. The effects on cell growth, cell cycle
      distribution, clonogenicity, survival, and the level and activity of HER-2/neu
      were examined. RESULTS: The combination of tamoxifen and Herceptin resulted in
      synergistic growth inhibition and enhancement of cell accumulation in the G(0)
      G(1) phase of the cell cycle, with a decrease in cells in S phase. Clonogenicity
      was inhibited in the presence of each drug and more so by the combination,
      although prior exposure to drugs did not affect subsequent clonogenicity in drug
      free media, and neither drug nor the combination induced apoptosis. Herceptin,
      but not tamoxifen, inhibited signaling by HER-2/neu. CONCLUSIONS: The combination
      of tamoxifen and Herceptin is formally demonstrated to result in synergistic
      growth inhibition and enhancement of G(0)-G(1) cell cycle accumulation. In vitro,
      the individual drugs or combination produces a cytostatic effect. These results
      suggest that combined inhibition of ER and HER-2/neu signaling may represent a
      powerful approach to the treatment of breast cancer.

PMID- 14977845
TI  - Generation of kidney cancer-specific antitumor immune responses using peripheral
      blood monocytes transduced with a recombinant adenovirus encoding carbonic
      anhydrase 9.
AB  - PURPOSE: Carbonic anhydrase 9 (CA9) is the most promising molecular marker
      described for renal cell carcinoma (RCC) to date. We investigated whether
      transduction of monocytes from peripheral blood with adenovirus encoding the CA9
      gene (AdV-CA9) could stimulate a T-cell mediated immune response against cancer
      cells expressing CA9. The ability to consistently generate a T-cell response is
      an important step toward the development of a CA9-specific RCC vaccine.
      EXPERIMENTAL DESIGN: AdV-CA9 was generated using the AdEasy system. AdV-CA9
      transduced peripheral blood mononuclear cell (PBMC)-derived monocytes were used
      to raise CTLs from autologous peripheral blood lymphocytes (PBLs). The ability of
      CTLs to lyse targets expressing CA9 was assessed by (51)Cr-release. RESULTS:
      Monocytes were efficiently transduced with AdV-CA9. In five of six experiments,
      AdV-CA9-transduced monocytes were able to induce a population of CTLs from bulk
      PBLs. CTLs were capable of lysing autologous, but not allogeneic monocytes
      expressing CA9. Furthermore, CTLs were able to lyse autologous RCC tumor cells
      expressing CA9. The ability of CTLs to lyse relevant targets was blocked by anti
      CD3, anti-CD8, and anti-MHC class I antibodies demonstrating a MHC class I
      restricted response. CONCLUSIONS: These results suggest that PBMC-derived
      monocytes transduced with AdV-CA9 can generate RCC-specific MHC class I
      restricted CTLs capable of lysing CA9-expressing cancer cells. Transduction of
      PBMC-derived monocytes with adenovirus provides a simple and effective
      alternative to the use of dendritic cells for the induction of antigen-specific
      CTL.

PMID- 14977846
TI  - An angiogenesis inhibitor E7820 shows broad-spectrum tumor growth inhibition in a
      xenograft model: possible value of integrin alpha2 on platelets as a biological
      marker.
AB  - We reported previously that an angiogenesis inhibitor, E7820, inhibits in vitro
      tube formation of human umbilical vein endothelial cell through the suppression
      of integrin alpha2 expression. Here we describe the antiangiogenic and antitumor
      effects of E7820 in mice and discuss the feasibility of using platelet integrin
      alpha2 expression on platelets as a biological marker of the efficacy of E7820.
      Oral administration of E7820 significantly inhibited basic fibroblast growth
      factor-induced angiogenesis in Matrigel implants and human colon WiDr tumor
      induced angiogenesis in a dorsal air sac model. Twice-daily treatment with E7820
      clearly inhibited the s.c. tumor growth of seven tumor cell lines derived from
      human colon, breast, pancreas, and kidney, and completely suppressed the growth
      of human pancreatic KP-1 and human colon LoVo cell lines. Moreover, E7820
      significantly inhibited the growth of KP-1 and human colon tumor Colo320DM cells
      orthotopically implanted in the pancreas and cecum, respectively. The efficacy of
      E7820 was comparable in the s.c. and orthotopic transplantation models.
      Immunohistochemical analyses using anti-CD31 antibody showed that E7820
      significantly reduced microvessel density in orthotopically implanted KP-1 tumor.
      E7820 reduced integrin alpha2 expression on a megakaryocytic cell line, Dami
      cells, induced by phorbol 12-myristate 13-acetate treatment. It also decreased
      the expression level of integrin alpha2 on platelets withdrawn from mice bearing
      s.c. KP-1 tumor at a dosage close to that affording antitumor activity. These
      data demonstrate that E7820 showed a broad-spectrum antitumor effect in mice
      through inhibition of angiogenesis and indicate that the decrease of integrin
      alpha2 on platelets might serve as a biological marker for the antitumor efficacy
      of E7820.

PMID- 14977847
TI  - A novel conditionally replicative adenovirus vector targeting telomerase-positive
      tumor cells.
AB  - PURPOSE: To develop a novel conditionally replicative adenovirus vector that
      targets telomerase-positive cancer cells. EXPERIMENTAL DESIGN: A telomerase gene
      derived promoter was used to control the expression of the E1a gene so that the
      E1a gene is only expressed in telomerase-positive tumor cells. In addition, a
      reporter gene was also engineered into the vector so that its infection and
      replication can be monitored easily. RESULTS: A novel recombinant adenovirus
      vector that could selectively replicate in telomerase-positive cancer cells was
      made successfully. This vector showed active replication in a panel of cancer
      cells and minimal replication in normal human fibroblast or epithelial cells. The
      recombinant vector could effectively lyse various cultured tumor cells even at
      very low multiplicity of infection. The replication efficiency in tumor cells is
      over 10(3)-fold more than normal fibroblast and epithelial cells. In s.c. tumor
      models, the newly developed telomerase-selective adenovirus vectors exhibited
      significantly more virus replication and reporter gene expression. CONCLUSIONS:
      The telomerase-targeted adenovirus vector has significant potential as an
      oncolytic virus as well as a tumor-specific therapeutic gene delivery vehicle.

PMID- 14977848
TI  - Comparative preclinical pharmacokinetic and metabolic studies of the
      combretastatin prodrugs combretastatin A4 phosphate and A1 phosphate.
AB  - PURPOSE: Combretastatin A4 phosphate (CA4P) and its structural analog,
      combretastatin A1 phosphate (CA1P), are soluble prodrugs capable of interacting
      with tubulin and causing rapid vascular shutdown within tumors. CA4P has
      completed Phase I clinical trials, but recent preclinical studies have shown that
      CA1P displays a greater antitumor effect than the combretastatin A4 (CA4) analog
      at equal doses. The aim of this study, therefore, is to compare pharmacokinetics
      and metabolism of the two compounds to determine whether pharmacokinetics plays a
      role in their differential activity. EXPERIMENTAL DESIGN: NMRI mice bearing MAC29
      tumors received injection with either CA4P or CA1P at a therapeutic dose of 150
      mg x kg(-1), and profiles of both compounds and their metabolites analyzed by a
      sensitive and specific liquid chromatography/mass spectroscopy method. RESULTS:
      The metabolic profile of both compounds is complex, with up to 14 metabolites
      being detected for combretastatin A1 (CA1) in the plasma. Many of these
      metabolites have been identified by liquid chromatography/mass spectroscopy.
      Initial studies, however, focused on the active components CA4 and CA1, where
      plasma and tumor areas under the curve were 18.4 and 60.1 microg x h x ml(-1) for
      CA4, and 10.4 and 13.1 microg x h x ml(-1) for CA1, respectively. In vitro
      metabolic comparisons of the two compounds strongly suggest that CA1 is
      metabolized to a more reactive species than the CA4. CONCLUSIONS: Although in
      vitro studies suggest that variable rates of tumor-specific prodrug
      dephosphorylation may explain these differences in pharmacokinetics profiles, the
      improved antitumor activity and altered pharmacokinetic profile of CA1 may be due
      to the formation of a more reactive metabolite.

PMID- 14977849
TI  - Adenovirus-mediated retinoblastoma 94 gene transfer induces human pancreatic
      tumor regression in a mouse xenograft model.
AB  - PURPOSE: Gene transfer of a truncated variant of the retinoblastoma (RB) gene
      encoding a M(r) 94000 protein that lacks the NH(2)-terminal 112 amino acid
      residues, termed RB94, has been shown to inhibit proliferation of several human
      tumor cell types. We have assessed its therapeutic effectiveness on pancreatic
      cancer, one of the most aggressive and therapy-resistant types of cancer. For
      this purpose, preclinical studies aimed to evaluate the therapeutic potential of
      RB94 gene transfer in pancreatic cancer were carried out. EXPERIMENTAL DESIGN: We
      have compared the antiproliferative effects of adenovirus-mediated gene transfer
      of RBwt and RB94 at the in vitro and in vivo levels in three RB-positive human
      pancreatic tumor cell lines: (a). NP-9; (b). NP-18; and (c). NP-31. We have also
      examined their effects on cell cycle and their capacity to induce apoptosis.
      RESULTS: In vitro results indicate that RB94 gene transfer has stronger
      antiproliferative effects compared with RBwt. RB94 transduction correlated with
      accumulation at the S-G(2) phase of the cell cycle in the three cell lines tested
      and induction of apoptosis in two of them. In vivo studies show significant
      decreases in the growth rate of tumors treated with Ad-RB94 when compared with
      those treated with Ad-RBwt. Moreover, terminal deoxynucleotidyl transferase
      mediated nick end labeling analyses of Ad-RB94-treated tumor sections revealed
      that only RB94 is able to significantly induce apoptosis. CONCLUSIONS: RB94 gene
      expression has antiproliferative effects also in human pancreatic tumor cells,
      being more effective than wild-type RB in preventing tumor growth.

PMID- 14977850
TI  - Tumor necrosis factor-related apoptosis-inducing ligand cooperates with
      anticancer drugs to overcome chemoresistance in antiapoptotic Bcl-2 family
      members expressing jurkat cells.
AB  - PURPOSE: Overexpression of antiapoptotic Bcl-2 family members has recently been
      related to resistance to chemo/radiotherapy in several human malignancies,
      particularly lymphomas. Hence, innovative approaches bypassing this resistance
      mechanism are required in the therapeutic approach. This study evaluated whether
      chemoresistance associated with Bcl-2 and Bcl-x(L) overexpression would be
      overcome by activating the death receptor pathway by tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) in the Jurkat cell model EXPERIMENTAL
      DESIGN: We made use of genetically modified Jurkat cells to evaluate the effect
      of Bcl-2 or Bcl-x(L) overexpression on the cytotoxic effect produced by the
      anticancer drugs doxorubicin, etoposide, and oxaliplatin and TRAIL. Caspase
      activation was detected by cleavage of caspase-8 and -3. The mitochondrial
      transmambrane potential was assessed by staining with DiOC(6) and flow cytometry.
      Caspase activity was blocked by the broad-spectrum caspase inhibitor zVAD-fmk.
      RESULTS: Bcl-2 and Bcl-x(L) overexpression but not lack of caspase-8 protects the
      Jurkat cells from the anticancer drug-induced cytolysis. However, Bcl-2/Bcl-x(L)
      Jurkat cells retained some susceptibility to TRAIL-induced cytolysis. A highly
      synergistic cytotoxic effect of the combination of TRAIL with any of the
      antiblastic used in this study was detected in the chemoresistant cells. This
      effect was associated with mitochondrial disassemblage and dependent on caspase
      activation CONCLUSIONS: The combination of TRAIL with conventional anticancer
      drugs may prove to be useful in the treatment of antiapoptotic Bcl-2 family
      proteins-expressing malignancies.

PMID- 14977851
TI  - The metabolism of pyrazoloacridine (NSC 366140) by cytochromes p450 and flavin
      monooxygenase in human liver microsomes.
AB  - Pyrazoloacridine (PZA) is an experimental antitumor agent presently under
      investigation for treatment of solid tumors on the basis of its unique mechanism
      of action and selectivity for human solid tumor xenograft in mice. Using
      capillary electrophoresis coupled with electrospray ionization mass spectrometry,
      we have identified three oxidative PZA metabolites, 9-desmethyl-PZA, N-demethyl
      PZA, and PZA N-oxide. The cytochrome p450 (CYP) isoforms involved in PZA
      metabolism were characterized by studies with CYP chemical inhibitors,
      correlation of marker activities for selected CYPs with formation of the
      metabolites using a human liver panel, and PZA metabolism by cDNA-expressed CYPs.
      9-Desmethyl-PZA formation was catalyzed by CYP1A2, whereas N-demethyl-PZA
      formation was catalyzed by CYP3A4. PZA N-oxide formation was catalyzed by flavin
      monooxygenase (FMO) rather than CYP, as determined by studies with chemical
      inhibitors of FMO and metabolism by cDNA-expressed human flavin monooxygenase.
      After administration of [10b-(14)C]PZA to mice, six urinary metabolites were
      detected by high-performance liquid chromatography UV and radiochromatograms
      including 9-desmethyl-PZA, N-demethyl-PZA, and PZA N-oxide. Trace concentrations
      of 9-desmethyl-PZA and PZA N-oxide were detected in mouse plasma. PZA N-oxide and
      N-demethyl-PZA were detected in urine from patients after PZA administration.
      PZA, 9-desmethyl-PZA, and PZA N-oxide inhibited growth of A375 human melanoma
      cells. IC(50) values were 0.17, 0.11, and 7.0 micro M, respectively, for the
      three molecules.

PMID- 14977852
TI  - Imexon-induced apoptosis in multiple myeloma tumor cells is caspase-8 dependent.
AB  - PURPOSE: Imexon is a 2-cyanoaziridine agent that has been shown to inhibit growth
      of chemotherapy-sensitive myeloma cells through apoptosis with decreased cellular
      stores of glutathione and increased reactive oxygen species (ROS). We examined
      the mechanism of imexon cytotoxicity in a diverse panel of dexamethasone and
      chemotherapy-sensitive and -resistant myeloma cell lines. EXPERIMENTAL DESIGN: We
      examined cellular cytotoxicity, apoptosis, and changes in redox state in
      dexamethasone-sensitive (C2E3), dexamethasone-resistant (1-310 and 1-414),
      chemotherapy-sensitive (RPMI-8226), and chemotherapy-resistant (DOX-1V and DOX
      10V) myeloma cell lines. RESULTS: We found significant cytotoxicity after 48-h
      incubation with imexon (80-160 microM) in dexamethasone and chemotherapy
      sensitive and -resistant myeloma cell lines in a time- and dose-dependent manner.
      The mechanism of imexon cytotoxicity in all cell lines was related to induction
      of apoptosis with the presence of cleaved caspase-3. Moreover, after imexon
      exposure in C2E3 and 1-414 cell lines, we demonstrated caspase-8-dependent
      apoptosis. Bcl-2:bax was proapoptotic with imexon in C2E3, whereas bcl-2:bax was
      independent of steroid resistance, chemotherapy sensitivity, and chemotherapy
      resistance. Depletion of intracellular glutathione was documented in RPMI-8226 at
      high imexon concentrations (>or=225 microM) but not in other cell lines.
      Furthermore, ROS were found in C2E3, RPMI-8226, and 1-310 only at high imexon
      concentrations, whereas a sensitive marker of oxidative DNA damage, 8
      hydroxydeoxyguanosine, was not increased in any cell line. CONCLUSIONS: Our
      results demonstrate that imexon has significant broad antimyeloma activity that
      is mediated through apoptotic mechanisms that is not dependent on production of
      ROS. Moreover, we have identified a mechanism of cytotoxicity in dexamethasone
      sensitive and -resistant myeloma cells induced by imexon that is caspase-8
      dependent.

PMID- 14977853
TI  - NADPH alkenal/one oxidoreductase activity determines sensitivity of cancer cells
      to the chemotherapeutic alkylating agent irofulven.
AB  - Illudins S and M are extremely cytotoxic products of the fungus Omphalotus
      illudens. They were evaluated as possible anticancer chemotherapeutic agents but
      displayed unfavorable therapeutic indices. Irofulven (6
      hydroxymethylacylfulvene), a less toxic, synthetic derivative of illudin S, has
      proven very effective in many preclinical and clinical studies. It has been
      postulated that metabolism via hydrogenation of the 8,9-double bonds of these
      molecules would unmask the electrophilic, and thus, the toxic nature of their
      cyclopropyl moieties. Illudins S and M were found to be rapidly metabolized by
      NADPH-dependent alkenal/one oxidoreductase (AOR) with maximal rates of 115.9 and
      44.1 micromol x min(-1) mg(-1), and K(m)s of 308 and 109 microM, respectively.
      Irofulven was reduced at a much slower rate: V(max) 275 nmol min(-1) mg(-1) and
      K(m) 145 microM. Human 293 cells transfected with an AOR overexpression vector
      were 100-fold more sensitive than control cells to irofulven, but displayed
      little differential sensitivity to illudin M. Addition of glutathione to the
      alpha,beta-unsaturated ketone moiety of illudin M, but not irofulven, occurred
      readily at physiological concentrations. Electrophilic intermediates of irofulven
      and illudin M that were activated by AOR were trapped with glutathione and
      identified by high performance liquid chromatography with tandem mass
      spectrometry. Samples of the 60 human tumor cell line panel used by the National
      Cancer Institute to evaluate potential chemotherapeutic compounds were assayed
      for AOR activity, which correlated positively with previously determined growth
      inhibitory measures for irofulven, but not illudin M or S. Collectively, these
      data indicate that bioactivation of irofulven by AOR plays a predominant role in
      its chemotherapeutic activity.

PMID- 14977854
TI  - Schedule-dependent cytotoxic interaction between epidoxorubicin and gemcitabine
      in human bladder cancer cells in vitro.
AB  - PURPOSE: The aim of the study was to evaluate the activity of epidoxorubicin
      (EPI) and gemcitabine (GEM) and to define the most effective schedule in human
      bladder cancer cells. EXPERIMENTAL DESIGN: The study was performed on HT1376 and
      MCR cell lines. Cells were exposed for 1 and 24 h to drugs used in different
      schemes. Cytotoxic activity was evaluated by the sulforhodamine B assay,
      potential clinical activity was estimated by relative antitumor activity, and the
      type of drug interaction was assessed using the method of Chou and Talalay. Cell
      cycle perturbations and apoptosis were assessed by flow cytometry; BAX, BCL-2,
      and P53 expression was evaluated by Western blot; and DNA damage was assessed
      using the alkaline Comet assay. RESULTS: EPI and GEM produced a cytotoxic effect
      in both cell lines, with 50% inhibitory concentration and relative antitumor
      activity values suggestive of a high clinical activity. Simultaneous treatment
      with EPI and GEM and the sequence GEM-->EPI caused an antagonistic interaction
      (combination index > 1) after both 1- and 24-h treatments. Conversely, the
      inverse sequence, EPI-->GEM, produced a synergistic interaction that was more
      pronounced in MCR cells than in HT1376 cells. The increase in DNA-damaged cells
      from 10% to 20% after single-drug exposure to 40-60% at the end of EPI-->GEM
      treatment may explain the synergistic interaction produced by the anthracycline
      antimetabolite sequence. CONCLUSIONS: Our findings show that the efficacy of the
      EPI and GEM combination is highly schedule dependent and indicate that the most
      active scheme is EPI followed by GEM, which is currently being validated in an
      ongoing intravesical Phase I-II clinical protocol.

PMID- 14977855
TI  - RWJ-241947 (MCC-555), a unique peroxisome proliferator-activated receptor-gamma
      ligand with antitumor activity against human prostate cancer in vitro and in
      beige/nude/ X-linked immunodeficient mice and enhancement of apoptosis in myeloma
      cells induced by arsenic trioxide.
AB  - PURPOSE: RWJ-241947 (MCC-555) is a novel peroxisome proliferator-activated
      receptor-gamma ligand of the thiazolidinedione class that was recently developed
      as an antidiabetic drug with unique properties. Some thiazolidinediones have
      anticancer activity against solid and hematological malignancies; the anticancer
      potency of RWJ-241947 has not been examined. We, therefore, investigated these
      effects in vitro and in vivo either alone or in combination with other compounds.
      EXPERIMENTAL DESIGN: Tumor growth was examined by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay, soft agar colony assay in vitro, and
      xenografts in nude mice. Its effects on cell cycle, differentiation, and
      apoptosis were examined. RESULTS: In vitro studies using various solid and
      hematological tumor cell lines showed that RWJ-241947 had antiproliferative
      activity against prostate cancer cells, with the strongest effect against the
      androgen-independent PC-3 prostate cancer cells. It increased expression of
      cyclin-dependent kinase inhibitor p21(WAF1), deceased cyclin E, and induced
      apoptosis in PC-3 cells. It increased E-cadherin and lowered protein expression
      of prostate-specific antigen without down-regulating the androgen receptor in
      androgen-dependent LNCaP prostate cancer cells. Reporter gene assays showed that
      this peroxisome proliferator-activated receptor-gamma ligand inhibited androgen
      activation of the androgen receptor response elements of the prostate-specific
      antigen gene. Remarkably, in vivo treatment of male beige/nude/X-linked
      immunodeficient (BNX) mice with RWJ-241947 profoundly suppressed growth of PC-3
      prostate cancer xenografts with prominent apoptosis, as well as fibrosis,
      including inflammatory and giant cell reaction in the remaining tumor tissue.
      Notably, the experimented mice had a significantly decreased cholesterol. In
      addition, we studied the combination of arsenic trioxide (As2O3), which is used
      in the treatment of multiple myeloma, and RWJ-241947; these two reagents together
      prominently inhibited proliferation and caused apoptosis of multiple myeloma
      cells. CONCLUSIONS: RWJ-241947 has surprisingly potent antiproliferative effects
      against prostate cancer cells in vivo, and it enhances the antitumor activity of
      As2O3 against myeloma cells. Small, well-defined clinical studies using RWJ
      241947 are in order for these cancers.

PMID- 14977856
TI  - Effect of a selective cyclooxygenase-2 inhibitor, nimesulide, on the growth of
      lung tumors and their expression of cyclooxygenase-2 and peroxisome proliferator-
      activated receptor-gamma.
AB  - PURPOSE: The objectives of this study were to evaluate the effect of a
      cyclooxygenase (COX)-2 inhibitor, nimesulide, on the growth inhibition of s.c.
      human lung A549 adenocarcinoma tumors and to assess the effect of nimesulide on
      the expression of COX-2 and peroxisome proliferator-activated receptor (PPAR)
      gamma in lung tumors harvested from mice. EXPERIMENTAL DESIGN: Female nu/nu mice
      were xenografted with s.c. A549 lung tumors, and 1 day after tumor implantation,
      the mice were fed with a diet containing nimesulide at 250-1500 ppm doses. Tumor
      dimensions were monitored twice weekly, and tumor samples isolated from mice were
      used to determine prostaglandin E(2) (PGE(2)) levels by enzyme immunoassay,
      expression of COX-2 and PPAR-gamma by Western blotting and immunohistochemistry.
      Furthermore, the induction of apoptosis in tumor specimens was determined by
      terminal deoxynucleotidyl transferase-mediated nick end labeling staining.
      RESULTS: Nimesulide treatment showed a dose-dependent growth-inhibitory effect of
      A549 tumors with a maximum of 77.7% inhibition at 1500 ppm of nimesulide. Western
      blotting experiments showed similar expression of COX-2 in both control and
      nimesulide (250-1500 ppm)-treated mice tumor tissues. PPAR-gamma was found to be
      overexpressed as a result of 1500 ppm nimesulide treatment and was not detected
      in tumors from control or 250-1000 ppm nimesulide-treated mice. Nimesulide (1500
      ppm) significantly reduced intratumor PGE(2) levels (P < 0.001) and induced
      apoptosis in 25% of tumor cells as compared with control tumors. CONCLUSIONS:
      Nimesulide (1500 ppm) induced growth inhibition of A549 lung tumors is associated
      with the reduction of intratumor PGE(2) levels but without affecting the
      expression of COX-2. Nimesulide-induced enhancement of the expression of PPAR
      gamma may also contribute to its antitumor effect, which needs to be further
      investigated.

PMID- 14977857
TI  - Long-term exposure to tamoxifen induces hypersensitivity to estradiol.
AB  - In women with hormone-dependent breast cancer, tamoxifen (TAM) frequently induces
      tumor regression, but regrowth occurs with continuation of antiestrogen therapy.
      Studies of breast xenografts in nude mice suggest that this secondary resistance
      to TAM may reflect the development of enhanced sensitivity to the estrogenic
      properties of TAM. In the current study, we examined the hypothesis that TAM
      could also induce a state of hypersensitivity to estradiol (E(2)) itself.
      Oophorectomized nude mice with MCF-7 cell xenografts received 25-mg implants of
      TAM [long-term TAM treated (LTTT) mice] or cholesterol (C-MCF-7) over a 5-month
      period (phase 1). The LTTT group regressed to a lesser extent than did C-MCF-7
      tumors. After 4 months of TAM exposure, the LTTT tumors begin to regrow, as did
      the C-MCF-7, as assessed by slope analysis. At 5 months, TAM or vehicle implants
      were removed, and the LTTT and C-MCF-7 subgroups were given vehicle or two doses
      of E(2) to test estrogen sensitivity (phase 2). We used our "E(2) clamp"
      technique to maintain levels of plasma E(2) at either 1.25 or 20 pg/ml. Neither
      group responded to the very low concentrations of E(2) (1.25 pg/ml) or vehicle.
      The LTTT tumors but not C-MCF-7 tumors exhibited a growth response on exposure to
      20 pg/ml E(2) during 7 weeks, as demonstrated with mixed models analysis. These
      studies provide evidence that long-term TAM exposure enhances sensitivity to the
      estrogenic effects of TAM and also to E(2) itself.

PMID- 14977858
TI  - Combined 5-fluorouracil/systemic interferon-beta gene therapy results in long
      term survival in mice with established colorectal liver metastases.
AB  - Preclinical in vitro and in vivo studies have demonstrated synergistic
      interactions between 5-fluorouracil (5-FU) and type I and II IFNs against human
      colorectal cancer cells. Despite these activities, randomized human trials have
      failed to identify a clinical benefit for this combination treatment. These
      limited clinical results may be secondary to the short half-life of recombinant
      IFN protein and the increased systemic toxicities of 5-FU/IFN combinations. We
      have previously reported an adenoviral-mediated IFN-beta gene therapy strategy,
      which may circumvent the pitfalls of recombinant IFN therapy. However, a dose
      dependent toxicity and acute inflammatory response to systemically administered
      adenovirus vectors may limit the clinical application of this therapy. The
      combination of adenoviral-mediated IFN-beta gene therapy and 5-FU resulted in
      tumor regression, apoptosis, and improved survival in an established liver
      metastases model. These therapeutic effects were observed at a significantly
      lower vector dose than we had previously reported and with limited toxicity. This
      approach may allow for an effective clinical application of this therapy and
      warrants additional investigation.

PMID- 14977859
TI  - Combination of an SRC kinase inhibitor with a novel pharmacological antagonist of
      the urokinase receptor diminishes in vitro colon cancer invasiveness.
AB  - PURPOSE: The urokinase-type plasminogen activator receptor (u-PAR) contributes to
      colon cancer invasion and metastases. We have shown previously that u-PAR
      expression in colon cancer is driven by the Src tyrosine kinase. In the current
      study, we determined the ability of PP2 (4-amino-5-(4-chlorophenyl)-7-(t
      butyl)pyrazolo[3,4-d]pyrimidine), a Src kinase inhibitor, to reduce u-PAR
      expression and colon cancer invasion. EXPERIMENTAL DESIGN: Western blotting,
      Northern blotting, and u-PAR promoter-reporter assays were performed to determine
      whether PP2 represses u-PAR expression. In vitro invasion assays were used to
      determine whether this kinase inhibitor, with or without a novel u-PAR
      antagonist, diminished cultured colon cancer invasiveness. RESULTS: A
      constitutively active c-Src increased in vitro invasiveness of SW480 cells,
      whereas HT-29 cells expressing antisense c-Src showed diminished invasiveness,
      validating c-Src as a target for low molecular weight compound(s). The Src
      inhibitor PP2 reduced u-PAR transcription in HT-29 cells over the concentration
      range that blocked Src kinase activity. PP2 also reduced u-PAR protein amounts in
      three other colon cancer cell lines with modest to high constitutive Src
      activity. Treatment of HT-29 cells and 2C8 cells (a SW480 clone expressing a
      constitutively active Src) with PP2 diminished their in vitro invasiveness.
      Furthermore, combination of the Src inhibitor with a novel u-PAR peptide
      antagonist (NI-5.12) proved superior to the individual agents in suppressing
      invasiveness. CONCLUSIONS: A c-Src kinase inhibitor represses u-PAR expression
      and, alone or in combination with a u-PAR antagonist, diminishes colon cancer
      invasiveness. Thus, concurrent targeting of c-Src expression and pharmacological
      blockade of the u-PAR may represent a novel means of controlling colon cancer
      spread.

PMID- 14977860
TI  - Thyroid hormone receptor-dependent transcriptional regulation of fibrinogen and
      coagulation proteins.
AB  - Thyroid hormone (T(3)) regulates growth, development, and differentiation. These
      activities are mediated by the nuclear thyroid hormone receptors (TRs), which
      belong to the steroid/TR superfamily of ligand-dependent transcription factors.
      The effect of T(3) treatment on target gene regulation was investigated in a
      TRalpha-overexpressing hepatoma cell line (HepG2-TRalpha), by performing cDNA
      microarrays. We demonstrate that 148 of the 7597 genes represented were up
      regulated by T(3), including fibrinogen and several other components of the
      coagulation factor system. To confirm the microarray results, fibrinogen and a
      small number of the blood clotting components were further investigated using
      quantitative RT-PCR. The T(3)-induction ratios observed with quantitative RT-PCR
      for factors such as thrombin (8-fold), coagulation factor X (4.9-fold), and
      hepatoglobin (30-fold) were similar to those observed by the cDNA microarray
      analysis. Further investigation, using HepG2-TRalpha (cell lines, revealed a 2-
      to 3-fold induction of fibrinogen transcription after 24 h of T(3) treatment. In
      addition, T(3) treatment increased the level of fibrinogen protein expression 2.5
      to 6-fold at 48 h. The protein synthesis inhibitor, cycloheximide, did not
      inhibit the induction of fibrinogen by T(3), indicating that this regulation was
      direct. Furthermore, transcription run-on experiments indicate that the induction
      of fibrinogen by T(3) is regulated largely at the level of transcription. Similar
      observations were made on the regulation of fibrinogen by T(3) using rats that
      received surgical thyroidectomy (TX) as an in vivo model. These results suggest
      that T(3) plays an important role in the process of blood coagulation and
      inflammation and may contribute to the understanding of the association between
      thyroid diseases and the misregulation of the inflammatory and clotting profile
      evident in the circulatory system of these patients.

PMID- 14977861
TI  - Glucuronidation and the UDP-glucuronosyltransferases in health and disease.
AB  - This article is an updated report of a symposium held at the June 2000 annual
      meeting of the American Society for Pharmacology and Experimental Therapeutics in
      Boston. The symposium was sponsored by the ASPET Divisions for Drug Metabolism
      and Molecular Pharmacology. The report covers research from the authors'
      laboratories on the structure and regulation of UDP-glucuronosyltransferase (UGT)
      genes, glucuronidation of xenobiotics and endobiotics, the toxicological
      relevance of UGTs, the role of UGT polymorphisms in cancer susceptibility, and
      gene therapy for UGT deficiencies.

PMID- 14977862
TI  - Involvement of organic anion transporting polypeptides in the transport of
      troglitazone sulfate: implications for understanding troglitazone hepatotoxicity.
AB  - Troglitazone is a thiazolidinedione insulin sensitizer drug that is metabolized
      mainly to a sulfate conjugate (M-1) in humans. It was reported to cause
      hepatotoxicity, although the cause has not been fully clarified. The objective of
      this study was to identify whether organic anion transporting polypeptide (OATP)
      transporters expressed at the basolateral membrane of human hepatocytes
      participate in troglitazone-associated hepatotoxicity. When OATP-B, OATP-C, or
      OATP8 was expressed in Xenopus oocytes, the transporter-mediated uptake into
      oocytes of troglitazone sulfate conjugate and the inhibitory effects of
      thiazolidinediones and the metabolites of troglitazone on estrone-3-sulfate
      transport were measured. M-1 was transported well by OATP-C but was not
      transported by OATP-B. OATP8 showed weak, but not statistically significant,
      transport of M-1. M-1 exhibited a strong inhibitory effect on estrone-3-sulfate
      transport by OATP-C and OATP8, suggesting a higher affinity than other
      thiazolidinediones and the metabolites of troglitazone, glucuronide conjugate and
      quinone metabolite. In conclusion, the sulfate conjugate of troglitazone has a
      higher affinity for OATPs than troglitazone itself or other metabolites. Since
      OATP transporters are important in the hepatic handling of bile acids, bilirubin,
      and other endogenous anionic compounds, M-1 may disturb the hepatic influx and
      efflux transport of these endogenous molecules across the basolateral membranes.
      Moreover, OATP-C may be involved in the hepatic toxicity of troglitazone through
      the inhibitory action of M-1.

PMID- 14977863
TI  - Impact of incubation conditions on bufuralol human clearance predictions: enzyme
      lability and nonspecific binding.
AB  - Human liver microsomes (HLMs) are frequently utilized in drug discovery to
      predict the human clearance of a compound. The extent to which the incubation
      conditions affect the accuracy of a human clearance prediction was determined for
      bufuralol. HLMs were preincubated at 37 degrees C for varying times (5-120 min)
      with and without NADPH, and the remaining enzyme activity was determined by
      incubating compounds that have been characterized to be selective for individual
      cytochromes P450 or flavin-containing monooxygenase 3. CYP2D6, the high-affinity
      component of bufuralol metabolism, was shown to be the least stable of the
      isoforms studied. The loss of CYP2D6 activity was further examined by determining
      the kinetics of 1'-hydroxybufuralol formation after different preincubation time
      periods, by using reactive oxygen species (ROS) scavengers, and by utilizing
      Western blotting techniques. A 3-fold decrease in Vmax was observed over 2 h,
      whereas the Km remained constant. ROS scavengers were able to block enzyme
      lability, and Western blots revealed no apparent loss of immunoreactive enzyme.
      The protein binding of bufuralol was determined in HLMs, recombinant CYP2D6, and
      human plasma. A prediction of theoretical bufuralol concentrations over a 120-min
      incubation that incorporated enzyme lability was performed and shown to be closer
      to actual data than if enzyme lability were ignored. Finally, a similar
      prediction using literature bufuralol data, coupled with the observed protein
      binding data, was used to illustrate that the most accurate predictions of
      bufuralol clearance are obtained when the amount of protein in the incubation is
      kept to a minimum and the overall incubation time is less than 20 min.

PMID- 14977864
TI  - Stereo- and regioselectivity account for the diversity of dehydroepiandrosterone
      (DHEA) metabolites produced by liver microsomal cytochromes P450.
AB  - The purpose of this study was to quantify the oxidative metabolism of
      dehydroepiandrosterone (3beta-hydroxy-androst-5-ene-17-one; DHEA) by liver
      microsomal fractions from various species and identify the cytochrome P450 (P450)
      enzymes responsible for production of individual hydroxylated DHEA metabolites. A
      gas chromatography-mass spectrometry method was developed for identification and
      quantification of DHEA metabolites. 7alpha-Hydroxy-DHEA was the major oxidative
      metabolite formed by rat (4.6 nmol/min/mg), hamster (7.4 nmol/min/mg), and pig
      (0.70 nmol/min/mg) liver microsomal fractions. 16alpha-Hydroxy-DHEA was the next
      most prevalent metabolite formed by rat (2.6 nmol/min/mg), hamster (0.26
      nmol/min/mg), and pig (0.16 nmol/min/mg). Several unidentified metabolites were
      formed by hamster liver microsomes, and androstenedione was produced only by pig
      microsomes. Liver microsomal fractions from one human demonstrated that DHEA was
      oxidatively metabolized at a total rate of 7.8 nmol/min/mg, forming 7alpha
      hydroxy-DHEA, 16alpha-hydroxy-DHEA, and a previously unidentified hydroxylated
      metabolite, 7beta-hydroxy-DHEA. Other human microsomal fractions exhibited much
      lower rates of metabolism, but with similar metabolite profiles. Recombinant
      P450s were used to identify the cytochrome P450s responsible for DHEA metabolism
      in the rat and human. CYP3A4 and CYP3A5 were the cytochromes P450 responsible for
      production of 7alpha-hydroxy-DHEA, 7beta-hydroxy-DHEA, and 16alpha-hydroxy-DHEA
      in adult liver microsomes, whereas the fetal/neonatal form CYP3A7 produced
      16alpha-hydroxy and 7beta-hydroxy-DHEA. CYP3A23 uniquely formed 7alpha-hydroxy
      DHEA, whereas other P450s, CYP2B1, CYP2C11, and CYP2D1, were responsible for
      16alpha-hydroxy-DHEA metabolite production in rat liver microsomal fractions.
      These results indicate that the stereo- and regioselectivity of hydroxylation by
      different P450s account for the diverse DHEA metabolites formed among various
      species.

PMID- 14977865
TI  - Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the
      glucuronidation of ezetimibe (Zetia).
AB  - Ezetimibe [1-(4-fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)
      (4-hydroxyphenyl)-2-azetidinone] (Zetia; Schering-Plough, Kenilworth, NJ) is the
      first in a new class of cholesterol-lowering agents known as cholesterol
      absorption inhibitors. The objective of this study was to identify the isoform(s)
      of human liver and intestinal UDP-glucuronosyltransferase (UGT) enzymes
      responsible for the glucuronidation of ezetimibe. The main circulating metabolite
      of this drug in human plasma is SCH 60663, the phenolic glucuronide conjugate of
      ezetimibe. SCH 60663 [m/z = 584 Thompsons (Th)] is also the major in vitro
      metabolite formed by human liver microsomes supplemented with UDP glucuronic acid
      (UDPGA). In contrast to the liver, human jejunum microsomes supplemented with
      UDPGA converted ezetimibe to two glucuronides with the same mass (m/z = 584 Th)
      by liquid chromatography-mass spectrometry. One corresponds to the phenolic
      glucuronide (1-O-[4-trans-2S,3R)-1-(4-fluorophenyl)-4-oxo-3-[3(S)-hydroxy-3-(4
      fluorophenyl)propyl]-2-azetidinyl]phenyl-beta-D-glucopyranuronic acid; SCH 60663)
      and the other was identified as the benzylic glucuronide of ezetimibe (1-O-[1(S)
      (4-fluorophenyl)-3-[1-(4-fluorophenyl)-2(S)-(4-hydroxyphenyl)-4-oxo-3(R)
      azetidinyl]propyl]-beta-D-glucopyranuronic acid; SCH 488128). Recombinant human
      UGT1A1, UGT1A3, and UGT2B15 all exhibited catalytic activity with respect to the
      formation of the phenolic glucuronide. However, UGT2B7 exclusively formed SCH
      488128, a trace metabolite detected in dog and human plasma samples after oral
      administration of ezetimibe. In conclusion, the formation of SCH 60663 is
      mediated via UGT1A1, UGT1A3, and UGT2B15, and the formation SCH 488128 is
      mediated via UGT2B7.

PMID- 14977866
TI  - Cytotoxicity of the novel glutathione-activated thiopurine prodrugs cis-AVTP [cis
      6-(2-acetylvinylthio)purine] and trans-AVTG [trans-6-(2-acetylvinylthio)guanine]
      results from the National Cancer Institute's anticancer drug screen.
AB  - cis-6-(2-Acetylvinylthio)purine (cis-AVTP) and trans-6-(2-acetylvinylthio)guanine
      (trans-AVTG) are glutathione-activated prodrugs of 6-mercaptopurine (6-MP) and 6
      thioguanine (6-TG), respectively. Previously, we showed that the prodrugs
      exhibited less in vivo toxicity in mice than did 6-TG, whereas their in vitro
      cytotoxicity in two renal cell carcinoma cell lines was comparable with or better
      than that of their respective thiopurines. To determine whether differences in
      sensitivity exist among different tissue types toward treatment with cis-AVTP and
      trans-AVTG, the cytotoxicity of the prodrugs was assessed in the National Cancer
      Institute's anticancer screening program, and the results were compared with the
      cytotoxicities of 6-MP and 6-TG obtained in the same screen. The results show
      that cis-AVTP was more cytotoxic than or equally cytotoxic as 6-MP. Similarly,
      trans-AVTG was in general more cytotoxic than 6-TG. Both prodrugs exhibited high
      growth-inhibitory activities in leukemic cells and melanoma cells. However, cis
      AVTP was more effective against renal cancer cells than trans-AVTG, whereas trans
      AVTG was more effective than cis-AVTP against ovarian cancer cells.
      Interestingly, analyses using the pattern-recognition algorithm COMPARE revealed
      that among all compounds in the database, the cytotoxic activity of both cis-AVTP
      and trans-AVTG correlated best with that of another thiopurine conjugate, NSC
      348401 (6-[(7-nitro-2,1,3-benzoxadiazol-4-yl)thio]-9H-purin-2-amine).
      Collectively, the results show that cis-AVTP and trans-AVTG exhibit both distinct
      and similar cytotoxicities toward different histotypes. Further investigations
      into the mechanisms responsible for these differences are warranted.

PMID- 14977867
TI  - An analysis of the regioselectivity of aromatic hydroxylation and N-oxygenation
      by cytochrome P450 enzymes.
AB  - Quinoline was used to probe the steric and electronic contributions to rates of
      aromatic oxidation of nitrogen-containing, multiring substrates by cytochrome
      P450 (P450) enzymes. The regioselectivity of the P450 oxidation of quinoline was
      determined experimentally by identifying and measuring the ratios of metabolites.
      The laboratory results were compared with those obtained computationally by
      modeling the electronic effects for aromatic hydroxylation of the substrate.
      Calculated values predict 8-hydroxyquinoline to have the lowest relative
      activation energy, whereas 3-hydroxyquinoline was calculated to have the highest
      relative activation energy. In contrast, 3-hydroxyquinoline was produced to a
      much greater extent relative to 8-hydroxyquinoline. The sharp contrast observed
      between the computationally obtained energies and the ratios of products
      identified experimentally indicates that steric factors play a role in
      determining the regioselectivity of P450 enzymes with quinoline. To further probe
      steric contributions to product formation, isoquinoline was used as a substrate
      and the results were compared with those obtained with quinoline. Isoquinoline N
      oxide was determined to be the major metabolite of isoquinoline with all of the
      P450 enzymes used. These results provide further evidence for the steric
      influence on the regioselectivity of P450 enzymes with quinoline.

PMID- 14977868
TI  - In vitro sulfoxidation of thioether compounds by human cytochrome P450 and flavin
      containing monooxygenase isoforms with particular reference to the CYP2C
      subfamily.
AB  - Cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) enzymes are
      major catalysts involved in the metabolism of xenobiotics. The sulfoxidation of
      the thioether pesticides, phorate, disulfoton, sulprofos, and methiocarb, was
      investigated. Using pooled human liver microsomes (HLMs), thioether compounds
      displayed similar affinities; however, phorate and disulfoton displayed higher
      intrinsic clearance rates than either sulprofos or methiocarb. The sulfoxidation
      of thioethers by HLMs was found to be predominantly P450-driven (85-90%) compared
      with FMO (10-15%). Among 16 cDNA-expressed human P450 isoforms and 3 human FMO
      isoforms examined, the following isoforms and their polymorphisms had the highest
      rates for sulfoxidation, as follows: phorate, CYP1A2, 3A4, 2B6, 2C9*1, 2C18,
      2C19, 2D6*1, and FMO1; disulfoton, CYP1A2, 3A4, 2B6, 2C9*1, 2C9*2, 2C18, 2C19,
      2D6*1, and FMO1; sulprofos, CYP1A1, 1A2, 3A4, 2C9*1, 2C9*2, 2C9*3, 2C18, 2C19,
      2D6*1, and FMO1; methiocarb, CYP1A1, 1A2, 3A4, 2B6, 2C9*1, 2C19, 2D6*1, and FMO1.
      Among these isoforms, members of the CYP2C subfamily often had the highest
      affinities and clearance rates. Moreover, sulfaphenazole, a CYP2C9 competitive
      inhibitor, inhibited disulfoton sulfoxidation by CYP2C9 (IC50 0.84 microM) as
      well as in HLMs. Ticlopidine, a CYP2C19 mechanism-based inhibitor, inhibited
      disulfoton sulfoxidation by CYP2C19 (IC50 after coincubation, 43.5 microM; IC50
      after preincubation, 4.3 microM) and also in HLMs. Our results indicate that
      current models of the substrate binding site of the CYP2C subfamily would not
      effectively predict thioether pesticide metabolism. Thus, the substrate
      specificity of CYP2Cs is more extensive than is currently believed, and some
      reevaluation of structure-activity relationships may be required.

PMID- 14977869
TI  - Human PXR variants and their differential effects on the regulation of human UDP
      glucuronosyltransferase gene expression.
AB  - The pregnane X receptor (PXR) has three known major transcript variants resulting
      from alternative splicing. The less well characterized variants T2 and T3 are
      identical to the well described variant T1 except for a 39-amino acid N-terminal
      extension in T2 and an internal 37-amino acid deletion in T3. We have developed
      reverse transcription-polymerase chain reaction (RT-PCR) methods to detect and
      quantify each human PXR (hPXR) in human liver and intestinal tissues and HepG2
      and Caco-2 cell lines. All three isoforms were expressed in hepatic cells,
      whereas only T1 transcripts were found in Caco-2 cells. In general, most normal
      human liver and intestinal mucosa contained all three hPXR variants, but
      considerable interindividual variation in expression levels was found. The effect
      of each hPXR variant on expression of UDP-glucuronosyltransferase (UGT) UGT1A and
      UGT2B family isoforms was investigated in transiently transfected HepG2 and Caco
      2 cells. As a family, UGT1A transcripts were up-regulated by T1 and T2 but not
      T3. Isoform-specific RT-PCR revealed that UGT1A1, 1A3, and 1A4 were the major
      isoforms induced in both cell lines. The levels of several UGT1A isoforms were
      also examined in human liver samples from a number of donors with characterized
      PXR expression. The data suggest that individual variation in PXR expression may
      account for differential expression of some UGT isoforms between subjects.

PMID- 14977870
TI  - Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers.
AB  - The objectives of this study were to evaluate the ability of 14 compounds, which
      differentially activate human pregnane X receptor (hPXR), to induce CYP2B6
      expression and to compare CYP2B6 and CYP3A4 concentration- and time-dependent
      induction by select inducers. Three primary human hepatocyte preparations were
      treated daily for 3 days with three concentrations of all compounds. Additional
      concentration- and/or time-response studies were conducted with clotrimazole,
      phenytoin, phenobarbital, and rifampin in six preparations. CYP2B6 and CYP3A4
      protein and activities were assessed by Western blotting, bupropion
      hydroxylation, and testosterone 6beta-hydroxylation, respectively. To evaluate
      hPXR activation by the 14 compounds, reporter gene assays were conducted using
      Huh7 cells cotransfected with hPXR and a CYP2B6 (NR1)5-LUC reporter plasmid.
      Clotrimazole, phenobarbital, rifampin, and ritonavir strongly induced CYP2B6 and
      activated hPXR; dexamethasone t-butylacetate and sulfinpyrazone induced CYP2B6
      weakly and activated hPXR moderately; paclitaxel strongly activated hPXR but did
      not increase CYP2B6 expression; carbamazepine and phenytoin moderately or
      strongly increased CYP2B6 expression but weakly activated hPXR; and
      dexamethasone, methotrexate, probenecid, sulfadimidine, and troleandomycin
      demonstrated weak or negligible effects on CYP2B6 and hPXR. EC50 values for
      CYP2B6 and CYP3A4 induction by clotrimazole, phenobarbital, phenytoin, and
      rifampin were strongly correlated (r2 = 0.99) and were statistically
      indistinguishable for clotrimazole, phenytoin, and rifampin. Kinetic constants
      governing time-dependent induction by phenobarbital and rifampin were also
      similar between CYP2B6 and CYP3A4. These results indicate that CYP2B6 is highly
      inducible by known CYP3A4 inducers and suggest that hPXR is a major determinant
      of CYP2B6-inducible expression for many, but not all, compounds evaluated in this
      study.

PMID- 14977871
TI  - Kupffer cell-mediated IL-2 suppression of CYP3A activity in human hepatocytes.
AB  - Interleukin (IL)-2 administration has been shown to decrease CYP3A enzyme
      activity in vivo. To determine whether IL-2 suppression of human hepatocyte CYP3A
      activity is direct or whether it is facilitated by the presence of Kupffer cells,
      primary human hepatocytes were cultured alone or cocultured with primary human
      Kupffer cells at physiologic hepatocyte/Kupffer cell ratios of 10:1 or 10:4.
      Using proinflammatory cytokines as positive controls, IL-1 (0.2-20 ng/ml) and IL
      6 (2-200 ng/ml) exposure resulted in a 70 to 90% decrease in CYP3A activity after
      72 h in hepatocyte cultures. In the hepatocyte/Kupffer cell cocultures, an 80%
      decrease in CYP3A activity was observed with IL-1 (2 ng/ml) or IL-6 (20 ng/ml),
      suggesting that direct suppressive effects of proinflammatory cytokines on
      hepatocyte CYP3A activity are not substantially altered by Kupffer cells. In
      contrast to the effects of these proinflammatory cytokines, no sustained
      suppression of CYP3A activity was observed with IL-2 (2-200 ng/ml) in hepatocyte
      cultures. However, in hepatocyte/Kupffer cell cocultures, a concentration
      dependent 50 to 70% suppression of CYP3A activity was observed with IL-2 at 72 h.
      In summary, these data suggest that Kupffer cells are required to reconstitute
      the suppressive effects of IL-2 on CYP3A activity that are observed in vivo and
      that hepatocyte/Kupffer cell cocultures may provide a useful model for
      investigating mechanisms of CYP3A4 regulation by cytokines. Of particular
      relevance to certain hepatic diseases, these findings suggest potential
      mechanisms whereby cytokines released from infiltrating blood mononuclear cells
      might modulate intercellular signaling and controls on hepatocyte function by
      various cell types that reside in liver.

PMID- 14977872
TI  - Is 17alpha-ethinyl estradiol an inhibitor of cytochrome P450 2C19?

PMID- 14977873
TI  - Muscle fat oxidative capacity is not impaired by age but by physical inactivity:
      association with insulin sensitivity.
AB  - The study aimed at determining whether aging and/or sedentariness impairs muscle
      fat oxidative capacity (OXFA) and whether this was associated with increased risk
      to develop insulin resistance. We first examined muscle mitochondrial functions,
      OXFA and insulin sensitivity (ISI; evaluated during an oral glucose tolerance
      test) in a cross-sectional study with 32 sedentary (S) and endurance-trained (T),
      young (Y) and elderly (E) men (24.2+/-2.6 vs. 66.6+/-3.2 yr). As for
      mitochondrial functions, OXFA was higher in T than in S but similar between age
      groups (SY 41.8+/-11.3, TY 68.0+/-17.7, SE 40.1+/-14.1, TE 73.1+/-20.1 palmitate
      x min(-1) x g wet tissue(-1); activity P<0.0001, age P=NS, activity x age P=NS).
      Similar results were obtained with ISI (SY 6.2+/-2.2, TY 11.4+/-4.4, SE 5.9+/
      1.5, TE 11.0+/-3.5, activity P<0.001, age P=NS, activity x age P=NS). Stepwise
      regression showed that, among body composition, VO2max and muscle biochemical
      characteristics, OXFA was the main predictor of ISI (r=0.60, P<0.001). We
      subsequently showed in eight sedentary elderly subjects (63.5+/-3.3 yr) that OXFA
      and insulin sensitivity (measured using insulin clamp) improved in parallel after
      8 weeks of endurance training (r=0.79, P<0.01). We concluded that mitochondrial
      functions, OXFA and ISI, are not impaired by age but by physical inactivity and
      are closely correlated.

PMID- 14977874
TI  - A new hypotensive polyunsaturated fatty acid dietary combination regulates oleic
      acid accumulation by suppression of stearoyl CoA desaturase 1 gene expression in
      the SHR model of genetic hypertension.
AB  - Polyunsaturated fatty acids (PUFA) are known to repress SCD-1 gene expression,
      key enzyme of monounsaturated fatty acid biosynthesis. Alterations of the
      monounsaturated/saturated fatty acids ratio have been implicated in various
      diseases related to the metabolic syndrome, including hypertension. We previously
      evidenced that lipogenesis end-products accumulated in spontaneously hypertensive
      rats (SHR), and that a dietary combination of n-6/n-3 PUFA had hypotensive
      effects. Our present objective was to test the hypothesis that these SHR liver
      lipid disorders might be modulated, in response to this hypotensive combination,
      by changes in SCD-1 expression and activity. So we studied, in hepatocytes, SCD-1
      transcription by Northern blotting, as well as plasma and liver fatty acid
      composition by gas-liquid chromatography. Liver SCD-1 gene expression was
      suppressed by 50%, and in different lipid classes, relative abundance of stearic
      and oleic acids decreased. Consequently, the Delta9 desaturation index,
      calculated from the ratio of oleic vs. stearic acids, decreased. In addition, the
      level of circulating saturated fatty acids decreased when one of oleic acids
      increased. These data provided evidence that the tested hypotensive PUFA
      combination reverses the high monounsaturated/saturated fatty acids ratio
      associated to hypertension in SHR, via a regulation monounsaturated fatty acid
      relative abundance by repression of SCD-1 gene.

PMID- 14977875
TI  - Loss of vagally mediated bradycardia and bronchoconstriction in mice lacking M2
      or M3 muscarinic acetylcholine receptors.
AB  - The presence of multiple muscarinic acetylcholine receptor (mAChR) subtypes in
      the heart and lung, combined with the lack of mAChR subtype-selective ligands,
      have complicated the task of identifying the mAChR subtypes mediating cardiac
      slowing (bradycardia) and airway narrowing (bronchoconstriction) due to vagal
      innervation. To determine which of the five mAChRs are responsible for the
      cholinergic control of heart rate and airway caliber in vivo, we performed
      experiments on mutant mice lacking the two prime candidates for such control, the
      M2 or M3 mAChR. Here, we report that in vivo, bradycardia caused by vagal
      stimulation or administration of the muscarinic agonist methacholine (MCh) was
      abolished in mice lacking functional M2 mAChRs (M2-/- mice). In contrast, heart
      rate responses remained unchanged in M3 receptor-deficient mice (M3-/- mice). The
      reduced hypotensive response of M3-/- mice to MCh suggests M3 mAChRs contribute
      to peripheral vasodilation. The M2-/- mice showed significantly enhanced in vivo
      bronchoconstrictor responses to vagal stimulation or MCh administration. In
      contrast, bronchoconstrictor responses were totally abolished in M3-/- mice.
      Because altered cardiac or pulmonary vagal tone is involved in a number of
      pathophysiological conditions, including cardiac arrhythmias, chronic obstructive
      pulmonary disease and asthma, these results should be of considerable therapeutic
      relevance.

PMID- 14977876
TI  - COX-2 inhibitors selectively block prostacyclin synthesis in endotoxin-exposed
      vascular smooth muscle cells.
AB  - High levels of prostacyclin (PGI2; measured as 6-keto-PGF1alpha) have been
      reported in patients under septic shock. Because this was at variance with our
      previous findings of nitration and inhibition of PGI2 synthase by endotoxin (LPS)
      in the endothelium, we examined the role of vascular smooth muscle as an
      alternative source of PGI2. Bovine aortic smooth muscle cells (SMC) in passage 1
      contained high levels of PGI2 synthase but no activity and no detectable levels
      of COX-1 or COX-2. LPS exposure for 3 h caused COX-2 mRNA and protein levels to
      rise during 8 h together with a large increase in PGI2 synthase activity. In
      contrast, cytokines lead to only a moderate increase of both PGI2 and PGE2.
      Specific COX-2 inhibitors completely blocked PGI2 formation but PGE2 synthesis
      only partially. Unexpectedly, *NO formation remained low over 6-8 h, which may be
      a reason for the lack of nitration and inhibition of prostacyclin synthase in LPS
      exposed SMC. Our results can explain the clinical observation of severe
      hypotension in progressive stages of septic shock as a mechanism to compensate
      endothelial dysfunction. According to our data, the use of COX-2-specific
      inhibitors may not be advisable in septic patients. In contrast, administration
      of COX-1-specific blockers could prevent platelet aggregation during progressed
      stages of endotoxic shock.

PMID- 14977877
TI  - Platelet-derived growth factor stimulates LAT1 gene expression in vascular smooth
      muscle: role in cell growth.
AB  - Platelet-derived growth factor (PDGF) contributes to vascular disease by
      stimulating the growth of vascular smooth muscle cells (SMCs). Since amino acids
      are required for cell growth, the present study examined the effect of PDGF on
      system L amino acid transport, which is the predominant cellular pathway for the
      uptake of essential amino acids. System L amino acid transport was monitored by
      measuring the uptake of L-leucine. Treatment of SMCs with PDGF stimulated L
      leucine transport in a concentration- and time-dependent manner, and this was
      associated with a selective increase in LAT1 mRNA and protein. PDGF failed to
      induce the expression of the other system L transport proteins, LAT2 and the
      heavy chain of the 4F2 cell surface antigen. The induction of LAT1 by PDGF was
      dependent on de novo RNA and protein synthesis and on mTOR activity. Serum,
      thrombin, and angiotensin II likewise stimulated L-leucine transport by inducing
      LAT1 expression. Inhibition of system L amino acid transport by the model
      substrate 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid blocked growth factor
      mediated SMC proliferation and induced SMC apoptosis, whereas it had no effect on
      quiescent cells. These results demonstrate that growth factors stimulate system L
      amino acid transport by inducing LAT1 gene expression and that system L amino
      acid transport is essential for SMC proliferation and survival. The capacity of
      vascular mitogens to induce LAT1 expression may represent a basic mechanism by
      which tho acid transport * apoptosis

PMID- 14977878
TI  - Biliverdin, a natural product of heme catabolism, induces tolerance to cardiac
      allografts.
AB  - Biliverdin, a product of heme oxygenase-1 (HO-1) enzymatic action, is converted
      into bilirubin, which has been considered a waste product in the past. We now
      show that administration of biliverdin has a salutary effect in organ
      transplantation. A brief course of treatment with biliverdin leads to long-term
      survival of H-2 incompatible heart allografts. Furthermore, those recipients
      harboring long-surviving (>100 days) allografts were tolerant to donor antigens
      indicated by the acceptance of second donor strain hearts but not third-party
      grafts. Treatment with biliverdin decreased intragraft leukocyte infiltration and
      inhibited T cell proliferation. Likely related to tolerance induction, biliverdin
      interferes with T cell signaling by inhibiting activation of nuclear factor of
      activated T cells (NFAT) and nuclear factor kappaB (NF-kappaB), two transcription
      factors involved in interleukin-2 (IL-2) transcription and T cell proliferation,
      as well as suppressing Th1 interferon-gamma (IFN-gamma) production in vitro.
      These findings support the potential use of biliverdin, a natural product, in
      transplantation and other T cell mediated immune disorders.

PMID- 14977879
TI  - Acute mechanoadaptation of vascular smooth muscle cells in response to continuous
      arteriolar vasoconstriction: implications for functional remodeling.
AB  - Arterioles exposed to norepinephrine (NE) for 4 h exhibit incomplete relaxation
      on removal of the agonist. We hypothesized that this is due to a
      mechanoadaptation process associated with active repositioning of vascular smooth
      muscle cells (VSMCs) within the vascular wall. Isolated arterioles were exposed
      to NE (10(-5.5) M) for either 5 min (n = 7) or 4 h (n = 13). During the 5-min
      exposure, vessel diameter was reduced to 61 +/- 2.6%, and cells shortened to 76.3
      +/- 3.8% of control. After NE removal, vessel diameter and cell length returned
      to control values, which indicated that during acute vasoconstriction cells
      shorten and relengthen in a reversible fashion. In contrast, when NE exposure
      lasted 4 h, vessels did not return to control diameter, but VSMCs returned to
      control length after NE removal. During the 4-h constriction, 56% of the VSMCs
      began returning to control length, and the overlap between VSMCs increased, which
      indicated that cellular repositioning had occurred in the presence of the
      maintained constriction. Thus, in response to prolonged constriction, VSMCs
      undergo a mechanoadaptation process involving "length autoregulation" that would
      be energetically favorable for maintenance of a reduced diameter and may provide
      a mechanism for the development of eutrophic remodeling of the vascular wall.

PMID- 14977880
TI  - Heme oxygenase-1-derived carbon monoxide protects hearts from transplant
      associated ischemia reperfusion injury.
AB  - Heme oxygenase-1 (HO-1) degrades heme into iron, biliverdin, and carbon monoxide
      (CO). HO-1 expression can be used therapeutically to ameliorate undesirable
      consequences of ischemia reperfusion injury (IRI), but the mechanism by which
      this occurs, remains to be established. Rat hearts, exposed to a prolonged period
      (24 h) of cold (4 degrees C) ischemia, failed to function upon transplantation
      into syngeneic recipients. Induction of HO-1 expression by administration of
      cobalt protoporphyrin IX (CoPPIX) to the graft donor restored graft function.
      Inhibition of HO-1 enzymatic activity, by administration of zinc protoporphyrin
      (ZnPPIX) at the time of transplantation, reversed the protective effect of HO-1.
      Exposure of the graft donor as well as the graft (during ischemia) to exogenous
      CO mimicked the protective effect of HO-1. This was associated with a significant
      reduction in the number of cells undergoing apoptosis in the graft with no
      apparent decrease of intravascular fibrin polymerization, platelet aggregation,
      or P-selectin expression. In conclusion, HO-1-derived CO prevents IRI associated
      with cardiac transplantation based on its antiapoptotic action. The observation
      that exposure of the donor and the graft to CO is sufficient to afford this
      protective effect should have important clinical implications in terms of
      preventing IRI associated with heart transplantation in humans.

PMID- 14977881
TI  - Apoptosis of endothelial cells triggers a caspase-dependent anti-apoptotic
      paracrine loop active on VSMC.
AB  - Increased endothelial apoptosis and decreased apoptosis of vascular smooth muscle
      cells (VSMC) are central to initiation of myo-intimal thickening. We hypothesized
      that apoptosis of endothelial cells (EC) induces the release of anti-apoptotic
      mediator(s) active on VSMC. We found that serum-free medium conditioned by
      apoptotic EC decreases apoptosis of VSMC compared with fresh serum-free medium.
      Inhibition of endothelial apoptosis during conditioning with a pan-caspase
      inhibitor ZVAD-FMK blocked the release of the anti-apoptotic factor(s) active on
      VSMC. VSMC exposed to serum-free medium conditioned by apoptotic EC showed
      increased ERK 1/2 phosphorylation, enhanced Bcl-xl expression, and inhibition of
      p53 expression. Fractionation of the conditioned medium followed by mass spectral
      analysis identified one bioactive component as a C-terminal fragment of the
      domain V of perlecan. Serum-free medium supplemented with either a synthetic
      peptide containing the EGF motif of the domain V of perlecan or chondroitin 4
      sulfate, a glycosaminoglycan anchored on the domain V of perlecan, increased ERK
      1/2 phosphorylation and Bcl-xl protein levels while inhibiting apoptosis of VSMC.
      These results suggest that a proteolytic activity developing downstream of
      activated caspases in apoptotic EC initiates degradation of pericellular
      proteoglycans and liberation of bioactive fragments with a robust impact on
      inhibition of VSMC apoptosis.

PMID- 14977882
TI  - Targeted gene delivery to sinusoidal endothelial cells: DNA nanoassociate bearing
      hyaluronan-glycocalyx.
AB  - Liver sinusoidal endothelial cells (SECs) possess unique receptors that recognize
      and internalize hyaluronic acid (HA). To develop a system for targeting foreign
      DNA to SECs, comb-type polycations having HA side chains were prepared by
      coupling HA to poly(L-lysine) (PLL). The HA-grafted-PLL copolymer (PLL-g-HA) thus
      formed was mixed with DNA in 154 mM NaCl to form soluble nanoassociates bearing
      hydrated hyaluronate shells. Agarose gel retardation assays revealed selective
      interaction of the PLL backbone with DNA despite the presence of polyanionic HA
      side chains. To determine whether the PLL-g-HA/DNA complexes were recognized by
      SEC HA receptors in vivo, we injected Wistar rats i.v. via the tail vein with PLL
      g-HA complexed to a beta-galactosidase expression plasmid (pSV beta-Gal) labeled
      with 32P. One hour postinjection, >90% of the injected radioactivity remained in
      the liver. Administration of the PLL-g-HA complexed to an FITC-labeled DNA
      revealed that the carrier-DNA complex was distributed exclusively in SECs. A
      large number of SECs expressing beta-galactosidase was detected along the
      sinusoidal lining after transfection with PLL-g-HA/pSV beta-Gal. Moreover, PLL-g
      HA effectively stabilized DNA triplex formation. In conclusion, the new PLL-g
      HA/DNA carrier system permits targeted transfer of exogenous genes selectively to
      the SECs.

PMID- 14977883
TI  - Semicarbazide sensitive amine oxidase overexpression has dual consequences:
      insulin mimicry and diabetes-like complications.
AB  - Semicarbazide-sensitive amine oxidases (SSAO) are copper-containing enzymes that
      oxidatively deaminate primary amines to produce hydrogen peroxide, ammonium, and
      specific aldehydes. Vascular adhesion protein-1 (VAP-1) is a cell surface and
      soluble molecule that possesses SSAO activity. VAP-1 protein, SSAO activity, and
      SSAO reaction products are elevated in the serum of patients with diabetes,
      congestive heart failure, and specific inflammatory liver diseases. By expressing
      human VAP-1/SSAO on mouse endothelial cells and subsequently in the serum, and by
      chronically treating the transgenic mice for 15 months with a high-fat diet and a
      physiological substrate for SSAO, methylamine, the in vivo roles of SSAO were
      assessed. The VAP-1 transgene increased the mouse body mass index and
      subcutaneous abdominal fat pad weights in a manner independent of food
      consumption. The transgene together with increased SSAO substrate availability
      enhanced glucose uptake in an SSAO-dependent manner. The increased SSAO activity
      also led to diabetes-like complications, including advanced glycation end product
      formation, elevated blood pressure, altered atherosclerosis progression, and
      nephropathy. These findings suggest that, although manipulation of VAP-1/SSAO has
      potential to serve as a therapeutic treatment in insulin-resistant conditions,
      care must be taken to fully understand its impact on obesity and vascular damage.

PMID- 14977884
TI  - Colonic leptin: source of a novel proinflammatory cytokine involved in IBD.
AB  - Leptin, a peptide encoded by the obese (ob) gene, is primarily secreted by
      adipocytes and is a critical hormone that controls body weight due to its central
      effects. Recently, additional roles for leptin in the gastrointestinal tract have
      been suggested because gastric lining cells also produce and release leptin in
      response to meal-related stimuli. While gastric epithelia might thus directly
      contribute to circulating leptin following a meal, here we show that inflamed
      colonic epithelial cells express and release leptin apically into the intestinal
      lumen. In addition, we demonstrate leptin expression and secretion in vitro in
      epithelial cells. In response to luminal leptin, model intestinal epithelia
      critically activate the NF-kappaB, a key signaling system to pro-inflammatory
      stimuli. The inflammatory effect of luminal leptin was characterized in vivo in
      mice administered intrarectal leptin. Leptin induced epithelial wall damage and
      neutrophil infiltration that represent characteristic histological findings in
      acute intestinal inflammation. These observations provide evidence for an
      intraluminal biological signaling of leptin and a new pathophysiological role for
      intraluminal leptin during states of intestinal inflammation such as inflammatory
      bowel disease.

PMID- 14977885
TI  - Profilin acts downstream of LDL to mediate diabetic endothelial cell dysfunction.
AB  - The changes occurring at the luminal surface of endothelial cells in diabetes and
      their relevance to endothelial dysfunction are poorly characterized in vivo. In
      this study, we developed an integrated strategy to discover cell surface proteins
      associated with diabetes and to test their role in endothelial dysfunction.
      First, a peptide phage display library was screened over the endothelial surface
      of the intact aorta or in retinal endothelial cells from diabetic and control
      rats. Then, we purified profilin-1 as a binding partner for one of the diabetic
      aorta-specific phage. Profilin was increased in the aortic endothelium of human
      diabetic individuals and streptozotocin-diabetic rats. Furthermore,
      overexpressing profilin in rat aortic endothelial cells triggered 3 indicators of
      endothelial dysfunction: increased apoptosis, elevated expression of ICAM-1, and
      decreased phosphorylation of the vasodilator-stimulated phosphoprotein, a marker
      for nitric oxide signaling. The changes in ICAM-1 and vasodilator-stimulated
      phosphoprotein were recapitulated in the diabetic aorta in vivo. LDL and
      oxysterols elevated profilin in cultured aortic endothelial cells. Interference
      with the de novo synthesis of profilin abrogated the LDL-mediated increase in
      ICAM-1 expression. Finally, profilin expression was markedly elevated in
      atherosclerotic plaques. These data indicate that profilin contributes to
      endothelial dysfunction in a pathway that is downstream of LDL.

PMID- 14977886
TI  - Factor VII-activating protease (FSAP) inhibits growth factor-mediated cell
      proliferation and migration of vascular smooth muscle cells.
AB  - The factor VII activating protease (FSAP) is a serine-protease present in human
      plasma that serves to activate single-chain plasminogen activators, as well as
      coagulation factor VII. FSAP was localized within atherosclerotic lesions, and a
      genetic polymorphism in FSAP is associated with carotid stenosis. Hence, this
      study was conducted to gain broader insights into the cellular effects of FSAP on
      vascular smooth muscle cells (VSMC). DNA synthesis and cell proliferation assays
      revealed an inhibitory action of FSAP on platelet-derived growth factor BB (PDGF
      BB)-mediated proliferation of VSMC. FSAP also inhibited PDGF-BB-induced migration
      of VSMC. These cellular effects of FSAP could be neutralized by an anti-FSAP mAb
      as well as by protease inhibitors such as aprotinin or a chloromethylketone
      inhibitor. Moreover, unfractionated heparin promoted the antiproliferative effect
      of FSAP on VSMC and was essential for the inhibition of VSMC migration. FSAP
      inhibited PDGF-BB binding to human VSMC and concomitantly blocked PDGF-BB
      dependent phosphorylation of mitogen activated protein kinase p42/p44 and
      tyrosine phosphorylation of other proteins. These results unravel a new function
      of FSAP as an inhibitor of the proatherogenic phenotype of vascular smooth
      muscle.

PMID- 14977887
TI  - The globular domains of PG-M/versican modulate the proliferation-apoptosis
      equilibrium and invasive capabilities of tumor cells.
AB  - To dissect the role of the globular domains of PGM/versican--a large hyaluronan
      binding proteoglycan (PG) enriched in tumor lesions--we have stably transduced a
      human leiomyosarcoma cell line with either the G1 or G3 domain of the PG and
      subsequently assayed the effect of this manipulation on several cellular
      processes in vitro and in vivo. G1- and G3-overexpressing cells were found to
      exhibit an enhanced growth that was more accentuated in the absence of serum
      components and was seen both when cells were cultured on ECM substrates and in
      the absence of ECM anchorage. Accordingly, if inoculated subcutaneously into nude
      mice, G1 transfectants formed larger tumor masses than control cells at the site
      of implantation, albeit after a certain latency period. Upon binding to cell
      surface CD44, proliferation of G1-, but not G3-, overexpressing cells were dose
      dependently inhibited by exogenous hyaluronan (HA) or HA fragments. G1- and G3
      transduced cells did not differ in their intrinsic ability to adhere and migrate
      on various purified ECM components, whereas G1-overproducing sarcoma cells were
      more invasive than the corresponding G3 mutants, and their locomotion was
      perturbed by exogenous HA. The augmented anchorage-independent growth exhibited
      solely by G1-transduced was largely ascribable to a reduced apoptotic rate,
      thereby indicating a shift in the proliferation--apoptosis equilibrium of the
      cells toward the former. In fact, G1-overexpressing cells appeared resistant to
      both cytotoxic drug-induced and Fas-dependent programmed cell death, and this
      resistance implicated mitochondrial apoptotic genes. The results indicate that
      the terminal domains of versican may differentially control propagation of tumor
      cells and diversely modulate their responses to environmental HA.

PMID- 14977888
TI  - Oxysterol mixtures prevent proapoptotic effects of 7-ketocholesterol in
      macrophages: implications for proatherogenic gene modulation.
AB  - Oxysterols are common components of oxidized low-density lipoprotein and
      accumulate in the core of fibrotic plaques as a mixture of cholesterol and
      cholesteryl ester oxidation products. The proapoptotic effects of a biologically
      representative mixture of oxysterols was compared with equimolar amounts of 7
      ketocholesterol and unoxidized cholesterol. The oxysterol mixture in a
      concentration range actually detectable in hypercholesterolemic patients did not
      stimulate programmed cell death in cultivated murine macrophages. Unoxidized
      cholesterol also produced no effect. By contrast, when given alone, 7
      ketocholesterol strongly stimulated the mitochondrial pathway of apoptosis with
      cytochrome c release, caspase-9 activation, and eventually caspase-3 activation.
      Subsequent experiments showed that when 7-ketocholesterol was administered to
      cells together with another oxysterol, namely 7betaOH-cholesterol, the strong
      proapoptotic effect of 7-ketocholesterol was markedly attenuated. As regards the
      mechanism underlying this quenching, we found that the combined oxysterol
      treatment counteracted the ability of 7-ketocholesterol, when administered alone,
      to strongly up-regulate the steady-state levels of reactive oxygen species (ROS)
      without interfering with sterol uptake. Furthermore, this increase in
      intracellular ROS appeared to be responsible for the up-regulation of
      proapoptotic factor, p21, after treatment with 7-ketocholesterol but not in cells
      challenged with the oxysterol mixture. Competition among oxysterols, apparently
      at the level of NADPH oxidase, diminishes the ROS induction and direct toxicity
      that is evoked by specific oxysterols. As a consequence, a more subtle gene
      modulation by oxysterols becomes facilitated in vascular cells.

PMID- 14977889
TI  - Postnatal steroid treatment and brain development.
AB  - This review examines the risk/benefit ratio of postnatal steroid treatment in
      preterm infants and correlates epidemiological data with experimental evidence on
      the effect of glucocorticosteroids on brain development.

PMID- 14977891
TI  - Management of fluid balance in the very immature neonate.
AB  - Preterm birth requires rapid adaptation from a liquid to a gaseous, low humidity
      environment. There are several ways in which this can be facilitated. The
      management of sodium and water balance is considered here.

PMID- 14977890
TI  - Neonatal transfusion practice.
AB  - Many previously widely accepted neonatal transfusion practices are changing as
      neonatologists become more aware of the risks to their patients of multiple blood
      product transfusions. Recent literature and research on neonatal transfusion
      practice are here reviewed, and practical guidelines and trigger thresholds for
      blood products commonly used in neonatal medicine are proposed.

PMID- 14977893
TI  - Lateralisation of language function in young adults born very preterm.
AB  - OBJECTIVE: To explore, using functional magnetic resonance imaging (MRI), the
      functional organisation of phonological processing in young adults born very
      preterm. SUBJECTS: Six right handed male subjects with radiological evidence of
      thinning of the corpus callosum were selected from a cohort of very preterm
      subjects. Six normal right handed male volunteers acted as controls. METHOD:
      Blood oxygenation level dependent contrast echoplanar images were acquired over
      five minutes at 1.5 T while subjects performed the tasks. During the ON
      condition, subjects were visually presented with pairs of non-words and asked to
      press a key when a pair of words rhymed (phonological processing). This task
      alternated with the OFF condition, which required subjects to make letter case
      judgments of visually presented pairs of consonant letter strings (orthographic
      processing). Generic brain activation maps were constructed from individual
      images by sinusoidal regression and non-parametric testing. Between group
      differences in the mean power of experimental response were identified on a voxel
      wise basis by analysis of variance. RESULTS: Compared with controls, the subjects
      with thinning of the corpus callosum showed significantly reduced power of
      response in the left hemisphere, including the peristriate cortex and the
      cerebellum, as well as in the right parietal association area. Significantly
      increased power of response was observed in the right precentral gyrus and the
      right supplementary motor area. CONCLUSIONS: The data show evidence of increased
      frontal and decreased occipital activation in male subjects with
      neurodevelopmental thinning of the corpus callosum, which may be due to the
      operation of developmental compensatory mechanisms.

PMID- 14977894
TI  - Transient adrenocortical insufficiency of prematurity and systemic hypotension in
      very low birthweight infants.
AB  - OBJECTIVES: A proportion of preterm, very low birthweight (VLBW, < 1500 g)
      infants may show inadequate adrenal response to stress in the immediate postnatal
      period. The human corticotrophin releasing hormone (hCRH) stimulation test was
      used to: (a) determine the relation between pituitary-adrenal response and
      systemic blood pressure in these infants; (b) characterise the endocrinological
      features of transient adrenocortical insufficiency of prematurity (TAP). STUDY
      DESIGN: A total of 226 hCRH tests were performed on 137 VLBW infants on day 7 and
      14 of life in a tertiary neonatal centre. RESULTS: Basal, peak, and incremental
      rise in serum cortisol (Delta Cort(0-30)) on day 7 were associated significantly
      with the lowest systolic, mean, and diastolic blood pressures recorded during the
      first two weeks of life (r > 0.25, p < 0.005). These cortisol concentrations also
      correlated significantly but negatively with the maximum and total cumulative
      dose of dopamine (r > -0.22, p < 0.02), dobutamine (r > -0.18, p < 0.04), and
      adrenaline (r > -0.26, p < 0.004), total volume of crystalloid (r > -0.22, p <
      0.02), and duration of inotrope treatment (r > -0.25, p < 0.006). Multivariate
      regression analysis of significant factors showed that the lowest systolic, mean,
      and diastolic blood pressures remained independently associated with serum
      cortisol (basal, peak, and Delta Cort(0-30)) on day 7. Hypotensive infants
      requiring inotropes (group 2) were significantly less mature and more sick than
      infants with normal blood pressure (group 1). The areas under the ACTH response
      curves were significantly greater in group 2 than in group 1, on both day 7 (p =
      0.004) and day 14 (p = 0.004). In contrast, the area under the cortisol response
      curve was significantly greater in group 1 than in group 2 on day 7 (p = 0.001),
      but there was no significant difference between the two groups on day 14. In
      addition, serum cortisol at the 50th centile in hypotensive infants had high
      specificity and positive predictive value (0.80-0.93 and 0.81-0.89 respectively)
      for predicting early neonatal hypotension. CONCLUSIONS: This study characterises
      the fundamental endocrinological features of TAP: normal or exaggerated pituitary
      response; adrenocortical insufficiency; good recovery of adrenal function by day
      14 of postnatal life. The results also provide the centiles of serum cortisol for
      hypotensive patients and infants with normal blood pressure, and show a
      significant relation between serum cortisol and blood pressure in VLBW infants.

PMID- 14977895
TI  - Early pituitary-adrenal response and respiratory outcomes in preterm infants.
AB  - OBJECTIVE: To assess the influence of circulating (basal) and stimulated plasma
      adrenocorticotrophin (ACTH) and serum cortisol on the duration of oxygen
      supplementation and development of chronic lung disease (CLD) in preterm, very
      low birthweight infants. METHODS: A total of 226 human corticotrophin releasing
      hormone stimulation tests were performed on 137 very low birthweight infants on
      days 7 and 14 in a tertiary neonatal centre. RESULTS: Multivariate regression
      analysis showed that the duration of oxygen supplementation was negatively
      associated with birth weight, but positively associated with alveolar-arterial
      oxygen gradient (A-aDO(2)) on the first day and with basal serum cortisol on day
      14. In addition, the multivariate classification and regression trees model
      indicated that the two most useful indices for predicting CLD were clinical risk
      index for babies (CRIB) score (> 9) and peak serum cortisol (> 740 nmol/l) on day
      14. The sensitivity, specificity, positive and negative predictive values of
      these factors for predicting CLD were 53%, 80%, 81%, and 70% respectively.
      CONCLUSIONS: The findings suggest that birth weight, severity of initial
      respiratory failure as reflected by the A-aDO(2) gradient, and continuing
      "stress" with persistent increase in serum cortisol on day 14 are significant
      risk factors associated with the duration of oxygen supplementation, whereas
      early pituitary-adrenal response (basal and peak plasma ACTH and serum cortisol
      on day 7) is not an independent risk factor. Although CRIB score in combination
      with peak serum cortisol on day 14 are useful predictors of CLD, the need to use
      a stimulation test and the relatively late timing of the forecast render these
      indices unattractive for routine clinical use.

PMID- 14977896
TI  - Maternal intravaginal prostaglandin E2 gel before elective caesarean section at
      term to induce catecholamine surge in cord blood: randomised, placebo controlled
      study.
AB  - OBJECTIVE: To test the hypothesis that the application of intravaginal
      prostaglandin E(2) gel before elective caesarean section (ECS) will induce a
      catecholamine surge in umbilical arterial blood. DESIGN: Randomised, double
      blind, placebo controlled trial. SETTING: A regional perinatal referral centre.
      PATIENTS: Mothers booked for ECS at or above 38 weeks gestation. INTERVENTIONS:
      Thirty six consenting mothers were randomly allocated to receive either 2 mg
      intravaginal prostaglandin E(2) gel (study group; n = 18) or an equal volume of K
      Y jelly as a placebo (control group; n = 18) 60 minutes before the ECS. Computer
      generated random numbers contained in coded, sealed envelopes were used for
      allocation. The obstetric and neonatal teams were blinded to the randomisation
      status of enrolled mothers. MAIN OUTCOME MEASURES: Catecholamine concentrations
      in the umbilical arterial blood samples collected at delivery. RESULTS: The
      median (interquartile range) neonatal gestation and birth weight were 271 (269
      274) days and 3605 (3072-3970) g for the study group and 271 (270-273) days and
      3340 (3000-3622) g for the control group. Median (interquartile range)
      noradrenaline (norepinephrine) concentrations in the umbilical arterial blood
      were significantly higher in the study group than the control group (15.9 (9.8
      28.92) v 4.6 (1.65-14.4) ng/l, p = 0.03). Adrenaline (epinephrine) concentrations
      did not differ significantly between the two groups (1.6 (< 0.5-3.1) v 1.4 (< 0.5
      2.75) ng/l, p = 0.6). No treatment related complications occurred. CONCLUSION: A
      labour related catecholamine surge could be simulated by intravaginal
      prostaglandin E(2) gel.

PMID- 14977897
TI  - Suppressive effects of breast milk on oxidative DNA damage in very low
      birthweight infants.
AB  - BACKGROUND: Human milk contains many kinds of antioxidant and is considered to
      prevent diseases mediated by oxygen free radicals in very low birthweight (VLBW)
      infants. AIMS: To examine the antioxidant effects of breast milk in VLBW infants
      by determining urinary 8-hydroxydeoxyguanosine (8-OHdG) excretion, which is known
      to be a non-invasive marker for in vivo oxidative DNA damage. METHODS: Urinary 8
      OHdG concentrations were measured in 15 breast fed and 14 formula fed VLBW
      infants at 2, 7, 14, and 28 days of age. RESULTS: Urinary 8-OHdG excretion at 14
      and 28 days of age was significantly lower than at 2 and 7 days of age in the
      breast fed group, and significantly lower than in the formula fed group.
      CONCLUSION: This is the first direct evidence of the antioxidant action of human
      milk in VLBW infants.

PMID- 14977898
TI  - Survival of very preterm infants: Epipage, a population based cohort study.
AB  - OBJECTIVE: To evaluate the outcome for all infants born before 33 weeks gestation
      until discharge from hospital. DESIGN: A prospective observational population
      based study. SETTING: Nine regions of France in 1997. PATIENTS: All births or
      late terminations of pregnancy for fetal or maternal reasons between 22 and 32
      weeks gestation. MAIN OUTCOME MEASURE: Life status: stillbirth, live birth, death
      in delivery room, death in intensive care, decision to limit intensive care,
      survival to discharge. RESULTS: A total of 722 late terminations, 772
      stillbirths, and 2901 live births were recorded. The incidence of very preterm
      births was 1.3 per 100 live births and stillbirths. The survival rate for births
      between 22 and 32 weeks was 67% of all births (including stillbirths), 85% of
      live births, and 89% of infants admitted to neonatal intensive care units.
      Survival increased with gestational age: 31% of all infants born alive at 24
      weeks survived to discharge, 78% at 28 weeks, and 97% at 32 weeks. Survival among
      live births was lower for small for gestational age infants, multiple births, and
      boys. Overall, 50% of deaths after birth followed decisions to withhold or
      withdraw intensive care: 66% of deaths in the delivery room, decreasing with
      increasing gestational age; 44% of deaths in the neonatal intensive care unit,
      with little variation with gestational age. CONCLUSION: Among very preterm
      babies, chances of survival varies greatly according to the length of gestation.
      At all gestational ages, a large proportion of deaths are associated with a
      decision to limit intensive care.

PMID- 14977899
TI  - Effect of birth order on neonatal morbidity and mortality among very low
      birthweight twins: a population based study.
AB  - OBJECTIVE: To study the effect of birth order on the risk for respiratory
      distress syndrome (RDS), chronic lung disease (CLD), adverse neurological
      findings, and death in very low birthweight (VLBW; < 1500 g) twins. METHODS: A
      population based study of VLBW infants from the Israel National VLBW Infant
      Database. The sample included all complete sets of VLBW twin pairs admitted to
      all 28 neonatal intensive care units between 1995 and 1999. Outcome variables
      were compared by birth order and stratified by mode of delivery and gestational
      age, using General Estimating Equation models, with results expressed as odds
      ratio (OR) with 95% confidence interval (CI). RESULTS: Second twins were at
      increased risk for RDS (OR 1.51, 95% CI 1.29 to 1.76), CLD (OR 1.36, 95% CI 1.11
      to 1.66), and death (OR 1.24, 95% CI 1.02 to 1.51) but not for adverse
      neurological findings (OR 1.20, 95% CI 0.91 to 1.60). Mode of delivery did not
      significantly influence outcome. The odds ratio for RDS in the second twin was
      inversely related to gestational age, and the increased risk for RDS and CLD was
      found in both vaginal and caesarean deliveries. CONCLUSIONS: VLBW second twins
      are at increased risk for acute and chronic lung disease and neonatal mortality,
      irrespective of mode of delivery.

PMID- 14977900
TI  - Prevalence of hypospadias and other genital anomalies among singleton births,
      1988-1997, in Scotland.
AB  - BACKGROUND: Considerable debate exists on the epidemiology of genital anomalies.
      METHODS: All genital anomalies, excluding undescended testes, were identified
      from neonatal returns, stillbirth and infant death survey records, and returns
      relating to hospital admissions and linked to form infant profiles on a cohort of
      singleton births between 1988 and 1997 with follow up for a minimum of three
      years. FINDINGS: The mean genital anomaly prevalence rate in Scotland was
      calculated at 4.6 per 1000 births varying from 4.0 per 1000 births in 1988 to 5.9
      per 1000 births in 1996. However, there was no evidence of a clear trend to an
      increasing prevalence of hypospadias, which constituted 73% of the anomalies
      studied. Logistic regression analysis of the data also showed this rate to be
      independently associated with being relatively small for gestational age (odds
      ratio (OR) 1.43, p < 0.001) and increasing maternal age (OR 1.2, p < 0.05).
      Infants born in deprived areas, as judged by the Carstairs deprivation score,
      were least likely to have a genital anomaly (OR 0.73, p < 0.01). INTERPRETATION:
      A new linked register of congenital genital anomalies in Scotland suggests that
      over a decade, the birth prevalence of genital anomalies has changed little. The
      associations between genital anomalies, maternal age, and socioeconomic
      deprivation require further study.

PMID- 14977901
TI  - Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic
      encephalopathy.
AB  - BACKGROUND: Multiorgan dysfunction (MOD) is one of four consensus based criteria
      for the diagnosis of intrapartum asphyxia. The theoretical concept behind MOD is
      the diving reflex (conservation of blood flow to vital organs at the cost of non
      vital organs). OBJECTIVES: To assess the patterns of involvement of each major
      organ/system and combinations of involvement in infants with post-asphyxial
      hypoxic-ischaemic encephalopathy (HIE), and to describe this in relation to long
      term outcome. DESIGN: Retrospective cohort study. SETTING: Regional tertiary
      neonatal intensive care unit at the Hospital for Sick Children, Toronto, Canada.
      PATIENTS: Term neonates with post-intrapartal asphyxial HIE assessed for kidney,
      cardiovascular system, lung, and liver function. OUTCOME: Death and presence or
      absence of severe neurodevelopmental disability. RESULTS: Out of 130 of 144
      eligible infants with outcome data, 80 (62%) had severe adverse outcome and 50
      (38%) had good outcome. All infants had evidence of MOD (at least one organ
      dysfunction in addition to HIE). Renal, cardiovascular, pulmonary, and hepatic
      dysfunction was present in 58-88% of infants with good outcome and 64-86% of
      infants with adverse outcome. CONCLUSIONS: MOD was present in all the infants
      with severe post-asphyxial HIE. However, there was no association between MOD and
      outcome in these infants. No relation between individual or combinations of organ
      involvements and long term outcomes was observed.

PMID- 14977902
TI  - Resuscitation with 100% O(2) does not protect the myocardium in hypoxic newborn
      piglets.
AB  - BACKGROUND: Perinatal asphyxia is associated with cardiac dysfunction secondary
      to myocardial ischaemia. Cardiac troponin I (cTnI) is a marker of myocardial
      necrosis. Raised concentrations in the blood are related to perinatal asphyxia
      and increased morbidity. OBJECTIVE: To assess porcine myocardial damage from
      enzyme release during hypoxaemia induced global ischaemia, and subsequent
      resuscitation with ambient air or 100% O(2). To investigate whether CO(2) level
      during resuscitation influences myocardial damage. DESIGN: Newborn piglets (12-36
      hours) were exposed to hypoxaemia by ventilation with 8% O(2) in nitrogen. When
      mean arterial blood pressure had fallen to 15 mm Hg, or base excess to < -20
      mmol/l, the animals were randomly resuscitated by ventilation with either 21%
      O(2) (group A, n = 29) or 100% O(2) (group B, n = 29) for 30 minutes. Afterwards
      they were observed in ambient air for another 150 minutes. During resuscitation,
      the two groups were further divided into three subgroups with different CO(2)
      levels. ANALYSIS: Blood samples were analysed for cTnI, myoglobin, and creatine
      kinase-myocardial band (CK-MB) at baseline and at the end of the study. RESULTS:
      cTnI increased more than 10-fold (p < 0.001) in all the groups. Myoglobin and CK
      MB doubled in concentration. CONCLUSION: The considerable increase in cTnI
      indicates seriously affected myocardium. Reoxygenation with 100% oxygen offered
      no biochemical benefit over ambient air. CK-MB and myoglobin were not reliable
      markers of myocardial damage. Normoventilation tended to produce better
      myocardial outcome than hyperventilation or hypoventilation.

PMID- 14977903
TI  - Nosocomial cutaneous abscesses in septic infants.
AB  - OBJECTIVE: To retrospectively study the epidemiology of nosocomial cutaneous
      abscesses in 46 consecutive septic infants. RESULTS: Ten infants had one abscess
      or more. Surviving infants with abscesses had a longer duration of bacteraemia,
      which disappeared within 24 hours of drainage. CONCLUSION: Infants with
      persistent bacteraemia should be examined regularly for the presence of
      abscesses.

PMID- 14977904
TI  - Infection with Ureaplasma urealyticum: is there a specific clinical and
      radiological course in the preterm infant?
AB  - BACKGROUND: Despite having mild early respiratory disease, many preterm babies
      develop chronic lung disease (CLD). Intrauterine infection with Ureaplasma
      urealyticum has been associated with preterm labour and CLD. OBJECTIVE: To test
      the hypothesis that infection with U urealyticum results in a specific clinical
      and radiological picture in the first 10 days of life. METHODS: Retrospective
      study of 60 ventilated babies < 30 weeks gestation, who had tracheal secretions
      tested for U urealyticum. Placental histology was reviewed by a paediatric
      pathologist for signs of chorioamnionitis. Chest radiographs were independently
      reviewed by two paediatric radiologists according to previously agreed criteria.
      All reviewers were blinded to the infection status of the babies. RESULTS: Twenty
      five babies were U urealyticum positive. These were more likely to experience
      chorioamnionitis (p = 0.004), premature rupture of membranes (p = 0.01), and
      spontaneous vaginal delivery (p = 0.09). U urealyticum positive babies had fewer
      signs of respiratory distress syndrome on early chest radiographs (p = 0.038),
      and they could be weaned from their ventilation settings (fraction of inspired
      oxygen (FIO(2)) and mean airway pressure) more quickly in the first few days.
      Subsequently U urealyticum positive babies deteriorated clinically and
      radiologically. More often they required ventilation to be restarted (p = 0.051),
      a higher proportion being ventilated on day 10 (p = 0.027) with higher FIO(2) (p
      = 0.001) and mean airway pressure (p = 0.002). Their chest radiographs showed
      more emphysematous changes as early as day 5 (p = 0.045), with a pronounced
      difference by day 10 (p = 0.009). CONCLUSIONS: Preterm ventilated babies with U
      urealyticum in their tracheal secretions have a different clinical and
      radiological course, with less acute lung disease but early onset of CLD,
      compared with those with negative cultures.

PMID- 14977905
TI  - Clinical detection of low upper body blood flow in very premature infants using
      blood pressure, capillary refill time, and central-peripheral temperature
      difference.
AB  - OBJECTIVE: To determine the accuracy of blood pressure (BP), capillary refill
      time (CRT), and central-peripheral temperature difference (CPTd) for detecting
      low upper body blood flow in the first day after birth. METHODS: A prospective,
      two centre cohort study of 128 infants born at < 30 weeks gestation. Invasive BP
      (n = 108), CRT (n = 128), and CPTd (n = 46) were performed immediately before
      echocardiographic measurement of superior vena cava (SVC) flow at three, 5-10,
      and 24 hours after birth. RESULTS: Forty four (34%) infants had low SVC flow (<
      41 ml/kg/min) in the first day, 13/122 (11%) at three hours, 39/126 (31%) at 5-10
      hours, and 4/119 (3%) at 24 hours. CPTd did not detect infants with low flows.
      Combining all observations in the first 24 hours, CRT > or = 3 seconds had 55%
      sensitivity and 81% specificity, mean BP < 30 mm Hg had 59% sensitivity and 77%
      specificity, and systolic BP < 40 mm Hg had 76% sensitivity and 68% specificity
      for detecting low SVC flow. Combining a mean BP < 30 mm Hg and/or central CRT >
      or = 3 seconds increases the sensitivity to 78%. CONCLUSIONS: Low upper body
      blood flow is common in the first day after birth and strongly associated with
      peri/intraventricular haemorrhage. BP and CRT are imperfect bedside tests for
      detecting low blood flow in the first day after birth.

PMID- 14977906
TI  - Accuracy of the volume and pressure displays of high frequency oscillators.
AB  - OBJECTIVE: To determine the effect of frequency on the accuracy of volume and
      pressure displays of high frequency oscillators. METHODS: The effect of frequency
      on the displayed volume of the Stephanie, Drager Babylog 8000 Plus, and SLE 5000
      oscillators was assessed. A sine wave pump delivered a constant tidal volume at
      frequencies of 5-15 Hz to the patient manifold of the oscillators. The displayed
      volumes at each frequency were compared with the delivered volume. The effect of
      frequency on displayed pressure was assessed by connecting the oscillator's
      patient manifold to a lung model; three types of oscillator were studied
      (SensorMedics 3100A, SLE 5000, and Stephanie). Airway pressure was measured from
      the manifold using a pressure transducer and non-compliant tubing; the pressure
      measuring system had a flat frequency response to 30 Hz. RESULTS: The SLE 5000
      volume display overread the delivered volume (by about 5%), but was not affected
      by frequency. At 5 Hz, the Drager Babylog 8000 Plus and the Stephanie underread
      the delivered volume (by about 20%). Increasing frequency resulted in a greater
      discrepancy between the delivered and displayed volume with the Stephanie, but a
      smaller discrepancy with the Drager Babylog 8000 Plus. Altering frequency had a
      small effect (maximum difference 6%) on the relation between the displayed and
      delivered pressure for all three oscillators. CONCLUSION: Frequency affects the
      accuracy of displayed volumes and, to a lesser extent, displayed pressures of
      high frequency oscillators. The results emphasise that data displayed by new
      devices should not be uncritically accepted.

PMID- 14977907
TI  - Nutritional effects on auditory brainstem maturation in healthy term infants.
AB  - OBJECTIVE: To assess the effects of dietary long chain polyunsaturated fatty acid
      (LCPUFA) supplementation on auditory brainstem maturation of healthy term
      newborns during the first 16 weeks of life by measuring brainstem auditory evoked
      potentials (BAEPs). DESIGN: Throughout the 16 week study period, infants in the
      formula A group (n = 28) were assigned to be fed exclusively with the same
      formula supplemented with DHA, and infants in the formula B group (n = 26) were
      assigned to receive only a DHA unsupplemented but otherwise similar formula.
      During the study period, the first 26 consecutive infants to be fed exclusively
      on their mother's milk for at least the first 16 weeks of life were chosen as the
      control group. BAEP measurements were performed twice: at the first and 16th week
      of age. RESULTS: There were no significant differences among the study and
      control groups in the BAEP measurements performed at the study entry. At 16 weeks
      of age, all absolute wave and interpeak latencies in the study and control groups
      had significantly decreased. The decreases were significantly greater in the
      formula A and control groups than in the formula B group. CONCLUSIONS: Infants
      fed on human milk or a formula supplemented with LCPUFAs during the first 16
      weeks of life show more rapid BAEP maturation than infants fed on a standard
      formula. Although the clinical importance and long term effects of these findings
      remain to be determined, routine supplementation of formulas with LCPUFAs should
      be considered.

PMID- 14977908
TI  - Measurement of urine output by weighing nappies.
AB  - The effect of humidity on measurement of neonatal urine output was assessed by
      weighing nappies in a clinically relevant context. Saline was used as dummy
      urine, on modern nappies in incubators at various humidity settings. In at least
      some additional humidity, no clinically relevant evaporative loss occurred.

PMID- 14977909
TI  - Cost effective use of satellite packs in neonates: importance of birth weight.
AB  - BACKGROUND: Blood banks split an adult packed red cell bag (usually 250 ml) into
      30 ml bags, making a total of eight neonatal "satellite" packs per donor. These
      packs are then "allocated"/"committed" to be used to serially transfuse a
      newborn. AIM: To study transfusion requirements of premature infants in relation
      to their birth weight and thereby attempt to rationalise the method of dispensing
      satellite blood packs. METHOD: Data on the distribution of neonatal transfusions
      with respect to weight were obtained retrospectively from unit A (51 infants, 168
      transfusions) and unit B (46 infants, 151 transfusions). These data were used to
      model the effect of different policies on donor exposure and number of unused
      packs. RESULTS: Infants weighing less than 1000 g at birth have significantly
      higher transfusion requirements than those weighing 1000 g or more (p = 0.001
      (unit A), p = 0.004 (unit B)). Our model predicted a significant reduction in
      donor exposure if eight packs/infant were allocated to those weighing < 1000 g,
      and a significant cut in the number of unused packs if four satellite
      packs/infant were allocated to those weighing > or = 1000 g. CONCLUSIONS: It
      would be safer and cost effective to allocate eight packs/infant to those with
      birth weights < 1000 g and four packs/infant to those with birth weights > or =
      1000 g.

PMID- 14977910
TI  - Probable adverse reaction to a pharmaceutical excipient.
AB  - Adverse reactions to medication are well recognised although information on the
      incidence in children is lacking. Adverse reactions have also been attributed to
      a range of pharmaceutical excipients. This is a report of an adverse reaction to
      the excipient in clindamycin injection.

PMID- 14977911
TI  - Louise Bourgeois (1563-1636): royal midwife of France.
AB  - Louise Bourgeois was the first practicing midwife to write of her experience of
      childbirth and of women's problems. She did much to enhance the respect in which
      her craft was held. For 26 years she was midwife to the royal court.

PMID- 14977912
TI  - Birth weight of Chinese babies born in Italy.

PMID- 14977914
TI  - Neonatal necrotising enterocolitis and perinatal exposure to co-amoxyclav.

PMID- 14977915
TI  - Gastric pneumatosis/interstitial emphysema of the stomach.

PMID- 14977918
TI  - Nuclear protein phosphatases with Kelch-repeat domains modulate the response to
      brassinosteroids in Arabidopsis.
AB  - Perception of the plant steroid hormone brassinolide (BL) by the membrane
      associated receptor kinase BRI1 triggers the dephosphorylation and accumulation
      in the nucleus of the transcriptional modulators BES1 and BZR1. We identified
      bsu1-1D as a dominant suppressor of bri1 in A abidopsis. BSU1 encodes a nuclear
      localized serine-threonine protein phosphatase with an N-terminal Kelch-repeat
      domain, and is preferentially expressed in elongating cells. BSU1 is able to
      modulate the phosphorylation state of BES1, counter acting the action of the
      glycogen synthase kinase-3 BIN2, and leading to inc eased steady-state levels of
      dephosphorylated BES1. BSU1 belongs to a small gene family; loss-of-function
      analyses unravel the extent of functional overlap among members of the family and
      confirm the role of these phosphatases in the control of cell elongation by BL.
      Our data indicate that BES1 is subject to antagonistic phosphorylation and
      dephosphorylation reactions in the nucleus, which fine-tune the amplitude of the
      response to BL.

PMID- 14977919
TI  - Nucleolar protein PinX1p regulates telomerase by sequestering its protein
      catalytic subunit in an inactive complex lacking telomerase RNA.
AB  - Human TRF1-binding protein PinX1 inhibits telomerase activity. Here we report
      that overexpression of yeast PinX1p (yPinX1p) results in shortened telomeres and
      decreased in vitro telomerase activity. yPinX1p coimmunoprecipitated with yeast
      telomerase protein Est2p even in cells lacking the telomerase RNA TLC1, or the
      telomerase-associated proteins Est1p and Est3p. Est2p regions required for
      binding to yPinX1p or TLC1 were similar. Furthermore, we found two distinct Est2p
      complexes exist, containing either yPinX1p or TLC1. Levels of Est2p-yPinX1p
      complex increased when TLC1 was deleted and decreased when TLC1 was
      overexpressed. Hence, we propose that yPinX1p regulates telomerase by
      sequestering its protein catalytic subunit in an inactive complex lacking
      telomerase RNA.

PMID- 14977920
TI  - The promoter of the Chinese hamster ovary dihydrofolate reductase gene regulates
      the activity of the local origin and helps define its boundaries.
AB  - The dihydrofolate reductase (DHFR) and 2BE2121 genes in the Chinese hamster are
      convergently transcribed in late G1 and ea ly S phase, and bracket an early
      firing origin of replication that consists of a 55-kb zone of potential
      initiation sites. To test whether transcription through the DHFR gene is required
      to activate this origin in early S phase, we examined the two-dimension (2D) gel
      patterns of replication intermediates from several variants in which parts or all
      of the DHFR promote had been deleted. In those variants in which transcription
      was undetectable, initiation in the intergenic space was markedly suppressed (but
      not eliminated) in early S phase. Further more, replication of the locus required
      virtually the entire S period, as opposed to the usual 3-4 h. However,
      restoration of transcription with either the wild-type Chinese hamster promote or
      a Drosophila-based construct restored origin activity to the wild-type pattern.
      Surprisingly, 2D gel analysis of promote less variants revealed that initiation
      occurs at a low level in ea ly S phase not only in the intergenic region, but
      also in the body of the DHFR gene. The latter phenomenon has never been observed
      in the wild-type locus. These studies suggest that transcription through the gene
      normally increases the efficiency of origin firing in early S phase, but also
      suppresses initiation in the body of the gene, thus helping to define the
      boundaries of the downstream origin.

PMID- 14977921
TI  - Dual roles of Sema6D in cardiac morphogenesis through region-specific association
      of its receptor, Plexin-A1, with off-track and vascular endothelial growth factor
      receptor type 2.
AB  - Semaphorins, originally identified as axon guidance facto s in the nervous
      system, play integral roles in organogenesis. Here, we demonstrate a critical
      involvement of Sema6D in cardiac morphogenesis. Ectopic expression of Sema6D o
      RNA interference against Sema6D induces expansion or narrowing of the ventricular
      chamber, respectively, during chick embryonic development. Sema6D also exerts
      region-specific activities on cardiac explants, a migration-promoting activity on
      outgrowing cells from the conotruncal segment, and a migration-inhibitory
      activity on those from the ventricle. Plexin-A1 mediates these activities as the
      major Sema6D-binding receptor. Plexin-A1 forms a receptor complex with vascular
      endothelial growth factor receptor type 2 in the conotruncal segment or with Off
      track in the ventricle segment; these complexes are responsible for the effects
      of Sema6D on the respective regions. Thus, the differential association of Plexin
      A1 with additional receptor components entitles Sema6D to exert distinct
      biological activities at adjacent regions. This is crucial for complex cardiac
      morphogenesis.

PMID- 14977922
TI  - Role of MyD88 in diminished tumor necrosis factor alpha production by newborn
      mononuclear cells in response to lipopolysaccharide.
AB  - Human newborns are more susceptible than adults to infection by gram-negative
      bacteria. We hypothesized that this susceptibility may be associated with a
      decreased response by leukocytes to lipopolysaccharide (LPS). In this study, we
      compared LPS-induced secretion of tumor necrosis factor alpha (TNF-alpha) by
      mononuclear cells (MNC) from adult peripheral blood and newborn umbilical cord
      blood in vitro and attempted to determine the mechanisms involved in its
      regulation. At a high concentration of LPS (10 ng/ml) and in the presence of
      autologous plasma, MNC from adults and newborns secreted similar amounts of TNF
      alpha. However, in the absence of plasma, MNC from newborns secreted
      significantly less TNF-alpha compared to MNC from adults. Moreover, at a low
      concentration of LPS (0.1 ng/ml) and in the presence of plasma, TNF-alpha
      secretion was significantly lower for newborn MNC compared to adult MNC. Adults
      and newborns had similar numbers of CD14 and Toll-like receptor 4 (TLR-4)
      positive cells as measured by flow cytometry. However, the intensity of the CD14
      marker was greater for adult than for newborn cells. Incubation of cells with LPS
      led to an increase in CD14 and TLR-4 intensity for adult cells but not for
      newborn cells. The effect of LPS stimulation of adult or newborn cells was
      similar for ERK, p38, and IkappaBalpha phosphorylation, as well as IkappaBalpha
      degradation. Finally, we assessed levels of the TLR-4 adapter protein, the
      myeloid differentiation antigen 88 (MyD88). We found a direct relation between
      adult and newborn TNF-alpha secretion and MyD88, which was significantly
      decreased in newborn monocytes. Since TLR-4 signals intracellularly through the
      adapter protein, MyD88, we hypothesize that MyD88-dependent factors are
      responsible for delayed and decreased TNF-alpha secretion in newborn monocytes.

PMID- 14977923
TI  - Contribution of long polar fimbriae to the virulence of rabbit-specific
      enteropathogenic Escherichia coli.
AB  - Enteropathogenic Escherichia coli (EPEC) is a major of cause of diarrhea among
      children in developing countries. Although EPEC is a human specific pathogen,
      some related strains are natural pathogens of animals, including laboratory-bred
      rabbits. We have identified two chromosomal loci in rabbit-specific EPEC (REPEC)
      O15:H- strain 83/39, which are predicted to encode long polar fimbriae (LPF).
      lpf(R154) was identical to a fimbrial gene cluster, lpf(O113), identified
      previously in enterohemorrhagic E. coli (EHEC) O113:H21. The second locus,
      lpf(R141), comprised a novel sequence with five predicted open reading frames,
      lpfA to lpfE, that encoded long fine fimbriae in nonfimbriated E. coli ORN103.
      The predicted products of lpf(R141) shared identity with components of the
      lpfABCC'DE gene cluster from EHEC O157:H7, and the fimbriae were similar in
      morphology and length to LPF from EHEC O157:H7. Interruption of lpf(R141)
      resulted in significant attenuation of REPEC 83/39 for rabbits with respect to
      the early stages of colonization and severity of diarrhea. However, there was no
      significant difference in the number of bacteria shed at later time points or in
      overall body weight and mortality rate of rabbits infected with lpf(R141) mutant
      strains or wild-type REPEC 83/39. Although rabbits infected with the lpf(R141)
      mutants did not develop severe diarrhea, there was evidence of attaching and
      effacing histopathology, which was indistinguishable in morphology, location, and
      extent compared to rabbits infected with wild-type REPEC 83/39. The results
      suggested that lpf(R141) contributes to the early stages of REPEC-mediated
      disease and that this is important for the development of severe diarrhea in
      susceptible animals.

PMID- 14977925
TI  - A type III secretion system is required for Aeromonas hydrophila AH-1
      pathogenesis.
AB  - Aeromonas hydrophila is a gram-negative opportunistic pathogen in fish and
      humans. Many bacterial pathogens of animals and plants have been shown to inject
      anti-host virulence determinants into the hosts via a type III secretion system
      (TTSS). Degenerate primers based on lcrD family genes that are present in every
      known TTSS allowed us to locate the TTSS gene cluster in A. hydrophila AH-1. A
      series of genome walking steps helped in the identification of 25 open reading
      frames that encode proteins homologous to those in TTSSs in other bacteria. PCR
      based analysis showed the presence of lcrD homologs (ascV) in all of the 33
      strains of A. hydrophila isolated from various sources. Insertional inactivation
      of two of the TTSS genes (aopB and aopD) led to decreased cytotoxicity in carp
      epithelial cells, increased phagocytosis, and reduced virulence in blue gourami.
      These results show that a TTSS is required for A. hydrophila pathogenesis. This
      is the first report of sequencing and characterization of TTSS gene clusters from
      A. hydrophila. The TTSS identified here may help in developing suitable vaccines
      as well as in further understanding of the pathogenesis of A. hydrophila.

PMID- 14977924
TI  - Sand fly saliva enhances Leishmania amazonensis infection by modulating
      interleukin-10 production.
AB  - After transmission through the bite of female sand flies, Leishmania spp. can
      cause a broad spectrum of disease manifestations collectively known as
      leishmaniases. L. amazonensis is endemic in South America, where it causes
      cutaneous, diffuse cutaneous, and visceral leishmaniasis. In this study, we have
      provided evidence that salivary gland extracts (SGE) of Lutzomyia longipalpis
      enhances L. amazonensis infection. BALB/c mice infected intradermally in the ear
      with 10(5) metacyclic promastigotes of L. amazonensis together with SGE
      (equivalent to 0.5 gland) showed an early onset of disease and larger lesions
      that contained approximately 3-log-units more parasites than did controls. To
      determine the potential mechanism underlying this enhancement, we assessed
      cytokine production via reverse transcriptase PCR and enzyme-linked immunosorbent
      assay. Mice coinjected with parasites and SGE displayed higher levels of
      interleukin-10 (IL-10) mRNA in the ear tissues, as well as higher levels of IL-10
      in supernatants of restimulated draining lymph node (LN) cells, than did
      controls. Flow cytometric analysis revealed high frequencies of IL-10-producing
      CD4(+) and CD8(+) T cells in the draining LN of mice coinjected with the parasite
      and SGE. In addition, we examined bone marrow derived-macrophage cultures and
      detected increased IL-10 but decreased nitric oxide (NO) production in cells
      exposed to SGE prior to infection with L. amazonensis. Together, these results
      imply that the sand fly saliva facilitates Leishmania evasion of the host immune
      system by modulating IL-10 production.

PMID- 14977926
TI  - STAT1 is essential for antimicrobial effector function but dispensable for gamma
      interferon production during Toxoplasma gondii infection.
AB  - The opportunistic protozoan Toxoplasma gondii is a prototypic Th1-inducing
      pathogen inducing strong gamma interferon (IFN-gamma) cytokine responses that are
      required to survive infection. Intracellular signaling intermediate STAT1
      mediates many effects of IFN-gamma and is implicated in activation of T-bet, a
      master regulator of Th1 differentiation. Here, we show that T. gondii-infected
      STAT1-null mice fail to upregulate the IFN-gamma-dependent effector molecules
      inducible nitric oxide synthase (iNOS), IGTP, and LRG-47, which are required for
      mice to survive infection. Both T-bet and interleukin-12 receptor beta2 (IL
      12Rbeta2) failed to undergo normal upregulation in response to T. gondii.
      Development of IFN-gamma-producing CD4(+) and CD8(+) T lymphocytes was severely
      curtailed in the absence of STAT1, but a substantial level of STAT1-independent
      non-T-cell-derived IFN-gamma was induced. Absence of STAT1 also resulted in
      increased IL-4, Arg1, Ym1, and Fizz1, markers of Th2 differentiation and
      alternative macrophage activation. Together, the results show that T. gondii
      induces STAT1-dependent T-lymphocyte and STAT1-independent non-T-cell IFN-gamma
      production, but that effector functions of this type 1 cytokine cannot operate in
      the absence of STAT1, resulting in extreme susceptibility to acute infection.

PMID- 14977927
TI  - A 38-kilobase pathogenicity island specific for Mycobacterium avium subsp.
      paratuberculosis encodes cell surface proteins expressed in the host.
AB  - We have used representational difference analysis to identify a novel
      Mycobacterium avium subsp. paratuberculosis-specific ABC transporter operon
      (mpt), which comprises six open reading frames designated mptA to -F and is
      immediately preceded by two putative Fur boxes. Functional genomics revealed that
      the mpt operon is flanked on one end by a fep cluster encoding proteins involved
      in the uptake of Fe(3+) and on the other end by a sid cluster encoding non
      ribosome-dependent heterocyclic siderophore synthases. Together these genes form
      a 38-kb M. avium subsp. paratuberculosis-specific locus flanked by an insertion
      sequence similar to IS1110. Expression studies using Western blot analyses showed
      that MptC is present in the envelope fraction of M. avium subsp.
      paratuberculosis. The MptD protein was shown to be surface exposed, using a
      specific phage (fMptD) isolated from a phage-peptide library, by differential
      screening of Mycobacterium smegmatis transformants. The phage fMptD-derived
      peptide could be used in a peptide-mediated capture PCR with milk from infected
      dairy herds, thereby showing surface-exposed expression of the MptD protein in
      the host. Together, these data suggest that the 38-kb locus constitutes an M.
      avium subsp. paratuberculosis pathogenicity island.

PMID- 14977928
TI  - Aerosolized gamma interferon (IFN-gamma) induces expression of the genes encoding
      the IFN-gamma-inducible 10-kilodalton protein but not inducible nitric oxide
      synthase in the lung during tuberculosis.
AB  - Gamma interferon (IFN-gamma) is critical in the immune response against
      Mycobacterium tuberculosis. In an ongoing trial of aerosol IFN-gamma in
      conjunction with standard drug therapy, we have observed activation of IFN
      signaling in bronchoalveolar lavage (BAL) cells from tuberculosis (TB) patients.
      We hypothesized that aerosol IFN-gamma treatment of pulmonary TB would increase
      expression of genes important for the control of TB. We investigated the
      expression of downstream genes by measuring inducible nitric oxide synthase
      (iNOS) and the chemokine IFN-inducible 10-kDa protein (IP-10) by real-time
      quantitative reverse transcription-PCR. In vitro, M. tuberculosis induced IP-10,
      and IFN-gamma stimulated this further, with no effect on iNOS expression. We
      studied 21 patients with pulmonary TB and 7 healthy subjects. Similar to the in
      vitro model, IP-10 mRNA was increased in BAL cells from TB patients and was
      augmented after treatment with aerosolized IFN-gamma. TB was also associated with
      elevated iNOS mRNA, but aerosolized IFN-gamma did not further enhance expression.
      Genomic analysis identified 1,300 of 4,058 genes expressed in BAL cells from six
      TB patients before and after 1 month of therapy, including aerosolized IFN-gamma.
      However, only 15 genes were differentially regulated by IFN-gamma. We conclude
      that iNOS and IP-10 mRNA expression is increased in TB but that aerosol IFN-gamma
      treatment increases expression of few genes in the human lung.

PMID- 14977929
TI  - Purification and analysis of a phospholipase A2-like lytic factor of Trichomonas
      vaginalis.
AB  - Trichomonas vaginalis produces soluble factors that have been reported to have
      the ability to damage target cells in vitro, and it has been hypothesized that
      these factors may play a role in the pathogenesis of human trichomoniasis. A
      lytic factor (LF) was purified from T. vaginalis, and the molecular
      characteristics of LF were determined. T. vaginalis extract was subjected to
      hydrophobic chromatography with a 10 to 60% N-propanol gradient in 0.1 M ammonium
      acetate, resulting in the elution of LF from the column at 30% N-propanol.
      Cytotoxicity assays revealed that LF was cytotoxic to WEHI 164 cells and bovine
      red blood cells, and inactivation of LF by treatment with trypsin suggested that
      the active component of LF was a protein. Size exclusion chromatography of LF
      produced two fractions at 144 and 168 kDa, and analysis by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of LF under reducing conditions revealed two
      subunits of 57 and 60 kDa. Results of a fluorescence assay of LF on
      carboxyfluorescein-labeled liposomes composed of phosphatidylcholine-cholesterol
      showed that liposomes were hydrolyzed, suggesting that LF had phospholipase
      activity. Thin-layer chromatography analysis of BODIPY (4,4-difluoro-3a,4adiaza-s
      indacene)-labeled phosphatidylcholine treated with LF demonstrated products that
      migrated identically to the products produced by treatment with phospholipase
      A(2) (PLA(2)). These results suggest that LF is a PLA(2) and may be an important
      virulence factor of T. vaginalis mediating the destruction of host cells and
      contributing to tissue damage and inflammation in trichomoniasis.

PMID- 14977930
TI  - Exogenous gamma and alpha/beta interferon rescues human macrophages from cell
      death induced by Bacillus anthracis.
AB  - During the recent bioterrorism-related outbreaks, inhalational anthrax had a 45%
      mortality in spite of appropriate antimicrobial therapy, underscoring the need
      for better adjuvant therapies. The variable latency between exposure and
      development of disease suggests an important role for the host's innate immune
      response. Alveolar macrophages are likely the first immune cells exposed to
      inhalational anthrax, and the interferon (IFN) response of these cells comprises
      an important arm of the host innate immune response to intracellular infection
      with Bacillus anthracis. Furthermore, IFNs have been used as immunoadjuvants for
      treatment of another intracellular pathogen, Mycobacterium tuberculosis. We
      established a model of B. anthracis infection with the Sterne strain (34F(2))
      which contains lethal toxin (LeTx). 34F(2) was lethal to murine and human
      macrophages. Treatment with IFNs significantly improved cell viability and
      reduced the number of germinated intracellular spores. Infection with 34F(2)
      failed to induce the latent transcription factors signal transducer and
      activators of transcription 1 (STAT1) and ISGF-3, which are central to the IFN
      response. Furthermore, 34F(2) reduced STAT1 activation in response to exogenous
      alpha/beta IFN, suggesting direct inhibition of IFN signaling. Even though 34F(2)
      has LeTx, there was no mitogen-activated protein kinase kinase 3 cleavage and p38
      was normally induced, suggesting that these early effects of B. anthracis
      infection in macrophages are independent of LeTx. These data suggest an important
      role for both IFNs in the control of B. anthracis and the potential benefit of
      using exogenous IFN as an immunoadjuvant therapy.

PMID- 14977931
TI  - Lutzomyia longipalpis salivary gland homogenate impairs cytokine production and
      costimulatory molecule expression on human monocytes and dendritic cells.
AB  - In this report, we describe an investigation of the effects of Lutzomyia
      longipalpis sand fly salivary gland homogenates (SGH) on cytokine production and
      expression of costimulatory molecules on human monocytes, macrophages (Mphis),
      and dendritic cells (DCs). SGH of L. longipalpis induced an increase in
      interleukin-6 (IL-6), IL-8 and IL-12p40 production but a decrease in tumor
      necrosis factor alpha and IL-10 production by lipopolysaccharida (LPS)-stimulated
      monocytes. We also examined the expression of costimulatory molecules on the
      surface of monocytes, Mphis, and DCs. Whereas SGH affected the expression of
      these molecules on monocytes and Mphis, it had little effect on these molecules
      on DCs. However, when DCs were generated from human monocytes in the presence of
      SGH, SGH inhibited the expression of costimulatory molecules. In addition, a
      decrease in the maturation of DCs induced by CD40L was observed in the presence
      of SGH. Finally, preincubating SGH with human sera containing anti-SGH-specific
      antibodies abolished the effects of SGH on cytokine production by LPS-stimulated
      monocytes.

PMID- 14977932
TI  - Cryptosporidium parvum-specific CD4 Th1 cells from sensitized donors responding
      to both fractionated and recombinant antigenic proteins.
AB  - T-cell-mediated immunity plays a central role in the host response to
      Cryptosporidium parvum. Human T-cell clones (TCC) were isolated from peripheral
      blood mononuclear cells of five healthy donors with prior cryptosporidiosis by
      use of a C. parvum crude extract, two antigen fractions obtained by ion-exchange
      chromatography (IEC1 and IEC2), and two recombinant peptides (SA35 and SA40) from
      C. parvum sporozoites. The T-cell lines derived from the one recently infected
      donor had a higher proportion (26 to 38%) of T cells exhibiting the gamma/delta T
      cell receptor (gamma/delta-TCR) than those from donors who had recovered from
      cryptosporidiosis several years earlier, suggesting that the gamma/delta T-cell
      population is involved in the early stage of the infection. The specific TCC had
      the alpha/beta-TCR, had the phenotype CD45RO(+) CD4(+) CD8(-), and were
      characterized by either hyperproduction of gamma interferon (IFN-gamma) alone,
      with a Th1 profile, or IFN-gamma hyperproduction together with interleukin-4 (IL
      4) or IL-5 production, with a Th0 profile. SA35, SA40, IEC1, and IEC2 may be
      considered good targets of the cellular response against C. parvum and may play a
      role in maintaining the T-cell-mediated memory response to this parasite.
      Furthermore, the SA35 and SA40 peptides may be regarded as immunodominant
      antigens involved in the maintenance of the T-cell response in healthy C. parvum
      sensitized persons.

PMID- 14977933
TI  - Organ injury and cytokine release caused by peptidoglycan are dependent on the
      structural integrity of the glycan chain.
AB  - Several studies have implicated a role of peptidoglycan (PepG) as a pathogenicity
      factor in sepsis and organ injury, in part by initiating the release of
      inflammatory mediators. We wanted to elucidate the structural requirements of
      PepG to trigger inflammatory responses and organ injury. Injection of native PepG
      into anesthetized rats caused moderate but significant increases in the levels of
      alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase,
      and bilirubin (markers of hepatic injury and/or dysfunction) and creatinine and
      urea (markers of renal dysfunction) in serum, whereas PepG pretreated with
      muramidase to digest the glycan backbone failed to do this. In an ex vivo model
      of human blood, PepG containing different amino acids induced similar levels of
      the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL
      8, and IL-10, as determined by plasma analyses (enzyme-linked immunosorbent
      assay). Hydrolysis of the Staphylococcus aureus cross-bridge with lysostaphin
      resulted in moderately reduced release of TNF-alpha, IL-6, IL-8, and IL-10,
      whereas muramidase digestion nearly abolished the ability to induce cytokine
      release and IL-6 mRNA accumulation in CD14(+) monocytes compared to intact PepG.
      However, additional experiments showed that muramidase-treated PepG synergized
      with lipopolysaccharide to induce TNF-alpha and IL-10 release in whole blood,
      despite its lack of inflammatory activity when administered alone. Based on these
      studies, we hypothesize that the structural integrity of the glycan chain of the
      PepG molecule is very important for the pathogenic effects of PepG. The amino
      acid composition of PepG, however, does not seem to be essential for the
      inflammatory properties of the molecule.

PMID- 14977935
TI  - Production of interleukin-8 by human neutrophils stimulated with Trichomonas
      vaginalis.
AB  - Neutrophils are the predominant inflammatory cells found in the vaginal
      discharges of patients infected with Trichomonas vaginalis. Although
      chemoattractants, such as leukotriene B(4) and interleukin-8 (IL-8), are found in
      the vaginal discharges of symptomatic trichomoniasis patients, little is known
      about the mechanism of how neutrophils accumulate or mediate initial inflammatory
      response after acute T. vaginalis infection. We examined IL-8 production in
      neutrophils activated by T. vaginalis and evaluated the factors involved in T.
      vaginalis adherence that might affect IL-8 production. When human neutrophils
      were stimulated with live trophozoites, T. vaginalis lysate, or T. vaginalis
      excretory-secretory products, the live trichomonads induced higher levels of IL-8
      production than the lysate or products did. When live trichomonads were
      pretreated with various inhibitors of proteinase, microtubule, microfilament, or
      adhesin (which are all known to participate in the adherence of T. vaginalis to
      vaginal epithelial cells), IL-8 production significantly decreased compared with
      the untreated controls. Furthermore, an NF-kappaB inhibitor (pyrrolidine
      dithiocarbamate), a mitogen-activated protein (MAP) kinase (MEK) inhibitor
      (PD98059), and a p38 MAP kinase inhibitor (SB203580) significantly suppressed IL
      8 synthesis in neutrophils. These results suggest that live T. vaginalis,
      particularly adherent trophozoites, can induce IL-8 production in neutrophils and
      that this action may be mediated through the NF-kappaB and MAP kinase signaling
      pathways. In other words, T. vaginalis-induced neutrophil recruitment may be
      mediated via the IL-8 expressed by neutrophils in response to activation by live
      T. vaginalis.

PMID- 14977934
TI  - Biological activities of Bacteroides forsythus lipoproteins and their possible
      pathological roles in periodontal disease.
AB  - Bacteroides forsythus is a gram-negative, anaerobic, fusiform bacterium and is
      considered to be an etiological agent in periodontal disease. A lipoprotein
      fraction prepared from B. forsythus cells by Triton X-114 phase separation (BfLP)
      activated human gingival fibroblasts and a human monocytic cell line, THP-1, to
      induce interleukin-6 production and tumor necrosis factor alpha production. BfLP
      was found to be capable of inducing nuclear factor-kappaB translocation in human
      gingival fibroblasts and THP-1 cells. By using Chinese hamster ovary K1 cells
      transfected with Toll-like receptor genes together with a nuclear factor-kappaB
      dependent CD25 reporter plasmid, it was found that signaling by BfLP was mediated
      by Toll-like receptor 2 but not by CD14 or Toll-like receptor 4. BfLP induced
      apoptotic cell death in human gingival fibroblasts, KB cells (an oral epithelial
      cell line), HL-60 cells (a human myeloid leukemia cell line), and THP-1 cells but
      not in MOLT4 cells (a T-cell leukemia cell line). Caspase-8, an initiator caspase
      in apoptosis, was found to be activated in these cells in response to BfLP
      stimulation. Thus, this study suggested that BfLP plays some etiological roles in
      oral infections, especially periodontal disease, by induction of cell activation
      or apoptosis.

PMID- 14977936
TI  - Identification of novel virulence-associated genes via genome analysis of
      hypothetical genes.
AB  - The sequencing of bacterial genomes has opened new perspectives for
      identification of targets for treatment of infectious diseases. We have
      identified a set of novel virulence-associated genes (vag genes) by comparing the
      genome sequences of six human pathogens that are known to cause persistent or
      chronic infections in humans: Yersinia pestis, Neisseria gonorrhoeae,
      Helicobacter pylori, Borrelia burgdorferi, Streptococcus pneumoniae, and
      Treponema pallidum. This comparison was limited to genes annotated as
      hypothetical in the T. pallidum genome project. Seventeen genes with unknown
      functions were found to be conserved among these pathogens. Insertional
      inactivation of 14 of these genes generated nine mutants that were attenuated for
      virulence in a mouse infection model. Out of these nine genes, five were found to
      be specifically associated with virulence in mice as demonstrated by infection
      with Yersinia pseudotuberculosis in-frame deletion mutants. In addition, these
      five vag genes were essential only in vivo, since all the mutants were able to
      grow in vitro. These genes are broadly conserved among bacteria. Therefore, we
      propose that the corresponding vag gene products may constitute novel targets for
      antimicrobial therapy and that some vag mutants could serve as carrier strains
      for live vaccines.

PMID- 14977937
TI  - Glyceraldehyde-3-phosphate dehydrogenase of Streptococcus oralis functions as a
      coadhesin for Porphyromonas gingivalis major fimbriae.
AB  - Cohesive interactions between Porphyromonas gingivalis and plaque-forming
      bacteria, such as Streptococcus oralis, are considered to play an important role
      in the colonization of P. gingivalis in periodontal sites. Although P. gingivalis
      fimbriae have been reported to mediate coaggregation with S. oralis, the S.
      oralis molecule involved has not been identified. We identified the coadhesin of
      S. oralis ATCC 9811 and purified it by affinity column chromatography. We found
      that the molecular mass of the purified protein was approximately 40 kDa. Dot
      blot and Western blot assays showed binding of the 40-kDa protein to P.
      gingivalis fimbriae. Further, turbidimetric assays showed that the coadhesin
      inhibited coaggregation between P. gingivalis and S. oralis in a dose-dependent
      manner. Analyses of the amino-terminal sequences of the protein and its lysyl
      endopeptidase-cleaved fragments revealed that the coadhesin was identical to
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Next, we cloned the gene that
      encodes S. oralis GAPDH and found that the sequence had a high degree of homology
      with the sequences of GAPDHs of various bacteria, including Streptococcus
      gordonii and Fusobacterium nucleatum. To confirm the contribution of S. oralis
      GAPDH to the interaction with P. gingivalis, a recombinant GAPDH protein was
      generated in Escherichia coli; this protein bound to P. gingivalis fimbriae and
      had an inhibitory effect on coaggregation. These results suggest that S. oralis
      GAPDH functions as a coadhesin for P. gingivalis fimbriae. In addition,
      considering the high degree of homology of the GAPDHs of various bacteria, those
      of other plaque-forming bacteria also may contribute to the colonization of P.
      gingivalis.

PMID- 14977938
TI  - Regulation of adenosine receptor subtypes during cultivation of human monocytes:
      role of receptors in preventing lipopolysaccharide-triggered respiratory burst.
AB  - Adenosine is a potent anti-inflammatory agent that modulates the function of
      cells involved in the inflammatory response. Here we show that it inhibits
      lipopolysaccharide (LPS)-induced formation of reactive oxygen intermediates (ROI)
      in both freshly isolated and cultured human monocytes. Blocking of adenosine
      uptake and inactivation of the adenosine-degrading enzyme adenosine deaminase
      enhanced the inhibitory action of adenosine, indicating that both pathways
      regulate the extracellular adenosine concentration. Adenosine-mediated inhibition
      could be reversed by XAC (xanthine amine congener), an antagonist of the
      adenosine receptor A(2A), and MRS 1220 [N-9-chloro-2-(2-furanyl)[1, 2, 4]
      triazolo[1,5-c]quinazolin-5-benzeneacetamide], an A(3) receptor antagonist, in
      both cell populations, while DPCPX (1,3-dipropyl-8-cyclopentylxanthine), an A(1)
      receptor antagonist, had no effect. Similar to what was seen with adenosine, CGS
      21680, an A(2A) and A(3) receptor agonist, and IB-MECA, a nonselective A(1) and
      A(3) receptor agonist, dose dependently prevented ROI formation, indicating the
      involvement of A(3) and probably also A(2A) in the suppressive effect of
      adenosine. Pretreatment of monocytes with adenosine did not lead to changes in
      the LPS-induced increase in intracellular calcium levels ([Ca(2+)](i)). Thus,
      participation of [Ca(2+)](i) in the action of adenosine seems unlikely. The
      adenosine-mediated suppression of ROI production was found to be more pronounced
      when monocytes were cultured for 18 h, a time point at which changes in the mRNA
      expression of adenosine receptors were observed. Most prominent was the increase
      in the A(2A) receptor mRNA. These data demonstrate that cultivation of monocytes
      is accompanied by changes in the inhibitory action of adenosine mediated by A(3)
      and probably also the A(2A) receptor and that regulation of adenosine receptors
      is an integral part of the monocyte differentiation program.

PMID- 14977939
TI  - Effect of neutralizing transforming growth factor beta1 on the immune response
      against Mycobacterium tuberculosis in guinea pigs.
AB  - Transforming growth factor beta (TGF-beta) is a cytokine which has been shown to
      suppress the antimycobacterial immune responses of humans and experimental
      animals. In this study, the contributions of TGF-beta to cytokine production in
      vivo were investigated by using the established guinea pig model of tuberculous
      pleurisy. Mycobacterium bovis BCG-vaccinated guinea pigs were injected
      intrapleurally with heat-killed virulent Mycobacterium tuberculosis. Eight days
      following induction of an antigen-specific pleural effusion, guinea pigs were
      injected intrapleurally with anti-TGF-beta1 or isotype control antibody. The
      following day, pleural exudates were removed, and the fluid volume and
      characteristics of the infiltrating cells were determined. Pleural fluid was
      analyzed for total interferon (IFN) and tumor necrosis factor (TNF) protein
      levels by using appropriate bioassays. RNA from pleural effusion cells was
      examined to determine TGF-beta1, TNF-alpha, IFN-gamma, and interleukin-8 mRNA
      levels by using real-time PCR. Proliferative responses of pleural effusion
      lymphocytes were examined in response to concanavalin A and purified protein
      derivative (PPD) in vitro. Treatment with anti-TGF-beta1 resulted in decreased
      pleural fluid volume and decreased cell numbers in the pleural space along with
      an increased percentage of lymphocytes and a decreased percentage of neutrophils.
      The bioactive TNF protein levels in pleural fluid were increased in guinea pigs
      treated with anti-TGF-beta1, while the bioactive IFN protein concentrations were
      not altered. Expression of TGF-beta1 and TNF-alpha mRNA was significantly
      increased following TGF-beta1 neutralization. Finally, PPD-induced proliferative
      responses of pleural cells from anti-TGF-beta1-treated animals were significantly
      enhanced. Thus, TGF-beta1 may be involved in the resolution of this local,
      mycobacterial antigen-specific inflammatory response.

PMID- 14977940
TI  - The DnaK/DnaJ chaperone machinery of Salmonella enterica serovar Typhimurium is
      essential for invasion of epithelial cells and survival within macrophages,
      leading to systemic infection.
AB  - Salmonella enterica serovar Typhimurium, similar to various facultative
      intracellular pathogens, has been shown to respond to the hostile conditions
      inside macrophages of the host organism by inducing stress proteins, such as
      DnaK. DnaK forms a chaperone machinery with the cochaperones DnaJ and GrpE. To
      elucidate the role of the DnaK chaperone machinery in the pathogenesis of S.
      enterica serovar Typhimurium, we first constructed an insertional mutation in the
      dnaK-dnaJ operon of pathogenic strain chi3306. The DnaK/DnaJ-depleted mutant was
      temperature sensitive for growth, that is, nonviable above 39 degrees C. We then
      isolated a spontaneously occurring revertant of the dnaK-dnaJ-disrupted mutant at
      39 degrees C and used it for infection of mice. The mutant lost the ability to
      cause a lethal systemic disease in mice. The impaired ability for virulence was
      restored when a functional copy of the dnaK-dnaJ operon was provided, suggesting
      that the DnaK/DnaJ chaperone machinery is required by Salmonella for the systemic
      infection of mice. This result also indicates that with respect to the DnaK/DnaJ
      chaperone machinery, the cellular requirements for growth at a high temperature
      are not identical to the cellular requirements for the pathogenesis of
      Salmonella. Macrophage survival assays revealed that the DnaK/DnaJ-depleted
      mutant could not survive or proliferate at all within macrophages. Of further
      interest are the findings that the mutant could neither invade cultured
      epithelial cells nor secrete any of the invasion proteins encoded within
      Salmonella pathogenicity island 1. This is the first time that the DnaK/DnaJ
      chaperone machinery has been shown to be involved in bacterial invasion of
      epithelial cells.

PMID- 14977941
TI  - Humoral responses to Porphyromonas gingivalis gingipain adhesin domains in
      subjects with chronic periodontitis.
AB  - The gingipains have been implicated in the pathogenicity of Porphyromonas
      gingivalis, a major etiologic agent of chronic periodontitis. Mature gingipains
      often present as a membrane-bound glycosylated proteinase-adhesin complex
      comprising multiple adhesin domains (HA1 to -4) and a catalytic domain. Using
      recombinant adhesin domains, we were able to show that patients with chronic
      periodontitis produce significantly more immunoglobulin G reactive with gingipain
      domains than a corresponding group with healthy periodontium. Titers were
      predominantly directed toward the carbohydrate epitopes shared between the
      gingipains and the lipopolysaccharide of P. gingivalis with little recognition of
      the peptide backbone of the catalytic domains. Distribution of titers to peptide
      epitopes of the adhesin domains was as follows: HA4 approximately HA1 > HA3 >>
      HA2. No correlation was observed between markers of disease severity and titers
      to individual adhesins within the disease group. Posttreatment titers showed no
      change or a decrease in titers for the majority of patients except for titers to
      the HA2 domain which showed marked increases in a few responding patients. Since
      the HA2 domain is important in hemoglobin binding and acquisition of essential
      porphyrin, boosting titers of antibodies to this domain may have the potential to
      control the growth of this organism.

PMID- 14977942
TI  - Effect of metabolic imbalance on expression of type III secretion genes in
      Pseudomonas aeruginosa.
AB  - The type III secretion system is a dedicated machinery used by many pathogens to
      deliver toxins directly into the cytoplasm of a target cell. Expression and
      secretion of the type III effectors are triggered by cell contact. In Pseudomonas
      aeruginosa and Yersinia spp., expression can be triggered in vitro by removing
      calcium from the medium. The mechanism underlying either mode of regulation is
      unclear. Here we characterize a transposon insertion mutant of P. aeruginosa PAO1
      that displays a marked defect in cytotoxicity. The insertion is located upstream
      of several genes involved in histidine utilization and impedes the ability of
      PAO1 to intoxicate eukaryotic cells effectively in a type III-dependent fashion.
      This inhibition depends on the presence of histidine in the medium and appears to
      depend on the excessive uptake and catabolism of histidine. The defect in
      cytotoxicity is mirrored by a decrease in exoS expression. Other parameters such
      as growth or piliation are unaffected. The cytotoxicity defect is partially
      complemented by an insertion mutation in cbrA that also causes overexpression of
      cbrB. The cbrAB two-component system has been implicated in sensing and
      responding to a carbon-nitrogen imbalance. Taken together, these results suggest
      that the metabolic state of the cell influences expression of the type III
      regulon.

PMID- 14977943
TI  - An NADPH quinone reductase of Helicobacter pylori plays an important role in
      oxidative stress resistance and host colonization.
AB  - Oxidative stress resistance is one of the key properties that enable pathogenic
      bacteria to survive the toxic reactive oxygen species released by the host. In a
      previous study characterizing oxidative stress resistance mutants of Helicobacter
      pylori, a novel potential antioxidant protein (MdaB) was identified by the
      observation that the expression of this protein was significantly upregulated to
      compensate for the loss of other major antioxidant components. In this study, we
      characterized an H. pylori mdaB mutant and the MdaB protein. While the wild-type
      strain can tolerate 10% oxygen for growth, the growth of the mdaB mutant was
      significantly inhibited by this oxygen condition. The mdaB mutant is also more
      sensitive to H(2)O(2), organic hydroperoxides, and the superoxide-generating
      agent paraquat. Although the wild-type strain can survive more than 10 h of air
      exposure, exposure of the mutant strain to air for 8 h resulted in recovery of no
      viable cells. The oxidative stress sensitivity of the mdaB mutant resulted in a
      deficiency in the ability to colonize mouse stomachs. H. pylori was recovered
      from 10 of 11 mouse stomachs inoculated with the wild-type strain, with about
      5,000 to 45,000 CFU/g of stomach. However, only 3 of 12 mice that were inoculated
      with the mdaB mutant strain were found to harbor any H. pylori, and these 3
      contained less than 2,000 CFU/g of stomach. A His-tagged MdaB protein was
      purified and characterized. It was shown to be a flavoprotein that catalyzes two
      electron transfer from NAD(P)H to quinones. It reduces both ubiquinones and
      menaquinones with similar efficiencies and preferably uses NADPH as an electron
      donor. We propose that the physiological function of the H. pylori MdaB protein
      is that of an NADPH quinone reductase that plays an important role in managing
      oxidative stress and contributes to successful colonization of the host.

PMID- 14977944
TI  - Role of NK cells and gamma interferon in transplacental passage of Toxoplasma
      gondii in a mouse model of primary infection.
AB  - Protective immunity in mice infected with Toxoplasma gondii is mainly mediated by
      NK cells, CD4 and CD8 T cells, and type 1 cytokines, such as gamma interferon
      (IFN-gamma). To clarify the roles of NK cells and IFN-gamma in protection against
      primary congenital toxoplasmosis, we used recombination activating gene 2
      knockout (RAG-2(-/-)) mice, which lack T and B lymphocytes, in comparison with
      the wild-type BALB/c model. RAG-2(-/-) mice had a significantly lower risk of
      fetal toxoplasmosis than BALB/c mice (25 versus 63.9%; P = 0.003). This
      protection was associated with an increased number of maternal NK cells, IFN
      gamma secretion by spleen cells, and decreased parasitemia. In the RAG-2(-/-)
      mice, NK cell depletion increased both the rate of fetal infection, to 56.5% (P =
      0.02), and the blood parasite burden. Conversely, in the BALB/c mice, this
      treatment did not modify maternofetal transmission or the blood parasite burden.
      Neutralization of IFN-gamma in both infected RAG-2(-/-) and BALB/c mice decreased
      congenital Toxoplasma transmission, contrasting with an exacerbation of maternal
      infection. These data suggest that a partially protective immunity against
      congenital toxoplasmosis is achieved due to the increased number of NK cells in
      RAG-2(-/-) mice. However, it seems that IFN-gamma enhances, directly or
      indirectly, the transplacental transmission.

PMID- 14977945
TI  - Survival of Aspergillus fumigatus in serum involves removal of iron from
      transferrin: the role of siderophores.
AB  - Aspergillus fumigatus is a filamentous fungus which can cause invasive disease in
      immunocompromised individuals. A. fumigatus can grow in medium containing up to
      80% human serum, despite very low concentrations of free iron. The purpose of
      this study was to determine the mechanism by which A. fumigatus obtains iron from
      the serum iron-binding protein transferrin. In iron-depleted minimal essential
      medium (MEM), A. fumigatus growth was supported by the addition of
      holotransferrin (holoTf) or FeCl(3) but not by the addition of apotransferrin
      (apoTf). Proteolytic degradation of transferrin by A. fumigatus occurred in MEM
      serum; however, transferrin degradation did not occur until late logarithmic
      phase. Moreover, transferrin was not degraded by A. fumigatus incubated in MEM
      holoTf. Urea polyacrylamide gel electrophoresis showed that in MEM-holoTf, holoTf
      was completely converted to apoTf by A. fumigatus. In human serum, all of the
      monoferric transferrin was converted to apoTf within 8 h. Siderophores were
      secreted by A. fumigatus after 8 h of growth in MEM-serum and 12 h in MEM-holoTf.
      The involvement of small molecules in iron acquisition was confirmed by the fact
      that transferrin was deferrated by A. fumigatus even when physically separated by
      a 12-kDa-cutoff membrane. Five siderophores were purified from A. fumigatus
      culture medium, and the two major siderophores were identified as
      triacetylfusarinine C and ferricrocin. Both triacetylfusarinine C and ferricrocin
      removed iron from holoTf with an affinity comparable to that of ferrichrome.
      These data indicate that A. fumigatus survival in human serum in vitro involves
      siderophore-mediated removal of iron from transferrin. Proteolytic degradation of
      transferrin may play a secondary role in iron acquisition.

PMID- 14977946
TI  - Cytokine gene expression in peripheral blood mononuclear cells and tissues of
      cattle infected with Mycobacterium avium subsp. paratuberculosis: evidence for an
      inherent proinflammatory gene expression pattern.
AB  - In cattle and other ruminants, infection with the intracellular pathogen
      Mycobacterium avium subsp. paratuberculosis results in a granulomatous enteritis
      (Johne's disease) that is often fatal. The key features of host immunity to M.
      avium subsp. paratuberculosis infection include an appropriate early
      proinflammatory and cytotoxic response (Th1-like) that eventually gives way to a
      predominant antibody-based response (Th2-like). Clinical disease symptoms often
      appear subsequent to waning of the Th1-like immune response. Understanding why
      this shift in the immune response occurs and the underlying molecular mechanisms
      involved is critical to future control measures and diagnosis. Previous studies
      have suggested that M. avium subsp. paratuberculosis may suppress gene expression
      in peripheral blood mononuclear cells (PBMCs) from infected cows, despite a
      continued inflammatory reaction at sites of infection. In the present study, we
      tested the hypothesis that exposure to M. avium subsp. paratuberculosis
      suppresses a proinflammatory gene expression pattern in PBMCs from infected cows.
      To do this, we examined expression of genes encoding interleukin-1alpha (IL
      1alpha), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p35, IL-16, and IL-18, as well
      as genes encoding gamma interferon (IFN-gamma), transforming growth factor beta
      (TGF-beta), and tumor necrosis factor alpha (TNF-alpha), in PBMCs, intestinal
      lesions, and mesenteric lymph nodes of cattle naturally infected with M. avium
      subsp. paratuberculosis. Cytokine gene expression in these cells and tissues was
      compared to expression in similar cells and tissues from control uninfected
      cattle. Our comprehensive results demonstrate that for most cytokine genes,
      including the genes encoding IFN-gamma, TGF-beta, TNF-alpha, IL-1alpha, IL-4, IL
      6, IL-8, and IL-12p35, differential expression in PBMCs from infected and control
      cattle did not require stimulation with M. avium subsp. paratuberculosis. In
      fact, stimulation with M. avium subsp. paratuberculosis tended to reduce the
      differential expression observed in infected and uninfected cows for genes
      encoding IFN-gamma, IL-1alpha, and IL-6. Only IL-10 gene expression was
      consistently enhanced by M. avium subsp. paratuberculosis stimulation of PBMCs
      from subclinically infected cattle. In ileal tissues from M. avium subsp.
      paratuberculosis-infected cattle, expression of the genes encoding IFN-gamma, TGF
      beta, IL-5, and IL-8 was greater than the expression in comparable tissues from
      control uninfected cattle, while expression of the gene encoding IL-16 was lower
      in tissues from infected cattle than in control tissues. Mesenteric lymph nodes
      draining sites of M. avium subsp. paratuberculosis infection expressed higher
      levels of IL-1alpha, IL-8, IL-2, and IL-10 mRNA than similar tissues from control
      uninfected cattle expressed. In contrast, the genes encoding TGF-beta and IL-16
      were expressed at lower levels in lymph nodes from infected cattle than in
      tissues from uninfected cattle. Taken together, our results suggest that cells or
      other mechanisms capable of limiting proinflammatory responses to M. avium subsp.
      paratuberculosis develop in infected cattle and that a likely place for
      development and expansion of these cell populations is the mesenteric lymph nodes
      draining sites of infection.

PMID- 14977947
TI  - The Klebsiella pneumoniae O antigen contributes to bacteremia and lethality
      during murine pneumonia.
AB  - Bacterial surface carbohydrates are important pathogenic factors in gram-negative
      pneumonia infections. Among these factors, O antigen has been reported to protect
      pathogens against complement-mediated killing. To examine further the role of O
      antigen, we insertionally inactivated the gene encoding a galactosyltransferase
      necessary for serotype O1 O-antigen synthesis (wbbO) from Klebsiella pneumoniae
      43816. Analysis of the mutant lipopolysaccharide by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis confirmed the absence of O antigen. In vitro,
      there were no detectable differences between wild-type K. pneumoniae and the O
      antigen-deficient mutant in regard to avid binding by murine complement C3 or
      resistance to serum- or whole-blood-mediated killing. Nevertheless, the 72-h 50%
      lethal dose of the wild-type strain was 30-fold greater than that of the mutant
      (2 x 10(3) versus 6 x 10(4) CFU) after intratracheal injection in ICR strain
      mice. Despite being less lethal, the mutant organism exhibited comparable
      intrapulmonary proliferation at 24 h compared to the level of the wild type.
      Whole-lung chemokine expression (CCL3 and CXCL2) and bronchoalveolar inflammatory
      cell content were also similar between the two infections. However, whereas the
      wild-type organism produced bacteremia within 24 h of infection in every
      instance, bacteremia was not seen in mutant-infected mice. These results suggest
      that during murine pneumonia caused by K. pneumoniae, O antigen contributes to
      lethality by increasing the propensity for bacteremia and not by significantly
      changing the early course of intrapulmonary infection.

PMID- 14977948
TI  - Effects of RelA on key virulence properties of planktonic and biofilm populations
      of Streptococcus mutans.
AB  - Streptococcus mutans is a biofilm-forming bacterium that is adapted to tolerate
      rapid and dramatic fluctuations in nutrient availability, carbohydrate source,
      and pH in its natural environment, the human oral cavity. Dissecting the pathways
      used to form stable biofilms and to tolerate environmental stress is central to
      understanding the virulence of this organism. Here, we investigated the role of
      the S. mutans relA gene, which codes for a guanosine tetraphosphate and guanosine
      pentaphosphate [(p)ppGpp] synthetase/hydrolase, in biofilm formation and acid
      tolerance. Two mutants in which relA was insertionally inactivated or replaced by
      an antibiotic resistance determinant were constructed. Under normal growth and
      stress conditions, the mutants grew slower than the wild-type strain, although
      the final yields were similar. The mutants, which were still able to accumulate
      (p)ppGpp after the induction of a stringent response, showed significant
      reductions in biofilm formation on microtiter plates or hydroxylapatite disks.
      There was no difference in the sensitivities to acid killing of the parent and
      relA strains grown in planktonic cultures. However, when cells were grown in
      biofilms, the mutants became more acid resistant and could lower the pH through
      glycolysis faster and to a greater extent than the wild-type strain. Differences
      in acid resistance were not correlated with increases in F-ATPase activity,
      although bacterial sugar:phosphotransferase activity was elevated in the mutants.
      Expression of the luxS gene was increased as much as fivefold in the relA
      mutants, suggesting a link between AI-2 quorum sensing and the stringent
      response.

PMID- 14977949
TI  - Invasion of porcine brain microvascular endothelial cells by Streptococcus suis
      serotype 2.
AB  - Streptococcus suis is an important swine pathogen that mainly causes meningitis
      and occasionally causes other infections, such as endocarditis, arthritis, and
      pneumonia. The pathogenesis of S. suis infection has not been completely defined.
      However, in order to cause meningitis, S. suis has to cross the blood-brain
      barrier (BBB) made up of brain microvascular endothelial cells. The objective of
      this work was to study the interactions of S. suis serotype 2 with porcine brain
      microvascular endothelial cells (PBMEC). The ability of North American and
      European S. suis serotype 2 strains to adhere to PBMEC and, most importantly, to
      invade PBMEC was demonstrated by using an antibiotic protection assay and was
      confirmed by electron microscopy. The polysaccharide capsule of S. suis seemed to
      partially interfere with the adhesion and invasion abilities of the bacterium.
      Our results showed that intracellular viable S. suis could be found in PBMEC up
      to 7 h after antibiotic treatment. Inhibition studies demonstrated that invasion
      of PBMEC by S. suis required actin microfilaments but not microtubular
      cytoskeletal elements or active bacterial RNA or protein synthesis. At high
      bacterial doses, suilysin-positive strains were toxic for PBMEC. The role of
      suilysin in cytotoxicity was confirmed by using purified suilysin, electron
      microscopy, and the lack of toxicity of a suilysin-negative mutant. In swine, the
      invasion of endothelial cells of the BBB could play an important role in the
      pathogenesis of the meningitis caused by S. suis.

PMID- 14977950
TI  - Bordetella pertussis infection of primary human monocytes alters HLA-DR
      expression.
AB  - Bordetella pertussis is the causative agent of whooping cough, a potentially
      lethal respiratory disease in children. In immunocompetent individuals, B.
      pertussis infection elicits an effective adaptive immune response driven by
      activated CD4(+) T cells. However, live B. pertussis persists in the host for 3
      to 4 weeks prior to clearance. Thus, B. pertussis appears to have evolved short
      term mechanisms for immune system evasion. We investigated the effects of B.
      pertussis wild-type strain BP338 on antigen presentation in primary human
      monocytes. BP338 infection reduced cell surface expression of HLA-DR and CD86 but
      not that of major histocompatibility complex class I proteins. This change in
      cell surface HLA-DR expression reflected intracellular redistribution of HLA-DR.
      The proportion of peptide-loaded molecules was unchanged in infected cells,
      suggesting that intracellular retention occurred after peptide loading. Although
      B. pertussis infection of monocytes induced rapid and robust expression of
      interleukin-10 (IL-10), HLA-DR redistribution did not appear to be explained by
      increased IL-10 levels. BP338-infected monocytes exhibited reduced synthesis of
      HLA-DR dimers. Interestingly, those HLA-DR proteins that were generated appeared
      to be longer-lived than HLA-DR in uninfected monocytes. BP338 infection also
      prevented gamma interferon (IFN-gamma) induction of HLA-DR protein synthesis.
      Using mutant strains of B. pertussis, we found that reduction in HLA-DR surface
      expression was due in part to the presence of pertussis toxin whereas the
      inhibition of IFN-gamma induction of HLA-DR could not be linked to any of the
      virulence factors tested. These data demonstrate that B. pertussis utilizes
      several mechanisms to modulate HLA-DR expression.

PMID- 14977951
TI  - Cross-species surface display of functional spirochetal lipoproteins by
      recombinant Borrelia burgdorferi.
AB  - Surface-exposed lipoproteins of relapsing fever (RF) and Lyme borreliosis
      Borrelia spirochetes mediate certain interactions of the bacteria with their
      arthropod and vertebrate hosts. RF spirochetes such as Borrelia hermsii serially
      evade the host's antibody response by multiphasic antigenic variation of Vsp and
      Vlp proteins. Furthermore, the expression of Vsp1 and Vsp2 by Borrelia turicatae
      is associated with neurotropism and higher blood densities, respectively. In
      contrast to RF Borrelia species, the Lyme borreliosis spirochete Borrelia
      burgdorferi is amenable to genetic manipulation. To facilitate structure-function
      analyses of RF surface lipoproteins, we used recombinant plasmids to introduce
      full-length vsp1 and vsp2 as well as two representative vlp genes into B.
      burgdorferi cells. Recombinant B. burgdorferi cells constitutively expressed the
      proteins under the control of the B. burgdorferi flaB promoter. Antibody and
      protease accessibility assays indicated proper surface exposure and folding.
      Expression of Vsp1 and Vsp2 conferred glycosaminoglycan binding to recombinant B.
      burgdorferi cells that was similar to that observed with purified recombinant
      proteins and B. turicatae expressing native Vsp. These data demonstrate that the
      lipoprotein modification and export mechanisms in the genus Borrelia are
      conserved. They also validate the use of recombinant B. burgdorferi in studies of
      surface lipoprotein structure-function and the biogenesis of spirochete
      membranes.

PMID- 14977952
TI  - Paneth cell alpha-defensins from rhesus macaque small intestine.
AB  - Antimicrobial peptides are secreted by small intestinal Paneth cells as
      components of innate immunity. To investigate the role of alpha-defensins in
      enteric host defenses in nonhuman primates, alpha-defensin cDNAs were isolated,
      alpha-defensin peptides were purified from rhesus macaque small bowel, and the
      bactericidal activities of the peptides were measured. Six rhesus enteric alpha
      defensin (RED) cDNAs, RED-1 to RED-6, were identified in a jejunum cDNA library;
      the deduced RED peptides exhibited extensive diversity relative to the primary
      structures of rhesus myeloid alpha-defensins. RED-4 was purified from monkey
      jejunum, and N-terminal peptide sequencing of putative RED-4 peptides identified
      two N termini, RTCYCRTGR. and TCYCRTGRC.; these corresponded to alternative N
      termini for the RED-4 molecules, as deduced from their molecular masses and RED
      cDNAs. In situ hybridization experiments localized RED mRNAs exclusively to small
      intestinal Paneth cells. Recombinant RED-1 to RED-4 were purified to homogeneity
      and shown to be microbicidal in the low micromolar range (</=10 micro g/ml)
      against gram-positive and gram-negative bacteria, with individual peptides
      exhibiting variable target cell specificities. Thus, compared to myeloid alpha
      defensins from rhesus macaques, enteric alpha-defensin peptides are highly
      variable in both primary structure and activity. These studies should facilitate
      further analyses of the role of alpha-defensins in primate enteric immunity.

PMID- 14977953
TI  - Nutritional effects on host response to lung infections with mucoid Pseudomonas
      aeruginosa in mice.
AB  - In cystic fibrosis, a recessive genetic disease caused by defects in the cystic
      fibrosis conductance regulator (CFTR), the main cause of death is lung infection
      and inflammation. Nutritional deficits have been proposed to contribute to the
      excessive host inflammatory response in both humans and Cftr-knockout mice. Cftr
      knockout mice and gut-corrected Cftr-knockout mice expressing human CFTR
      primarily in the gut were challenged with Pseudomonas aeruginosa-laden agarose
      beads; they responded similarly with respect to bronchoalveolar lavage cell
      counts and levels of the acute-phase cytokines tumor necrosis factor alpha,
      interleukin-1beta (IL-1beta), and IL-6. Wild-type mice fed the liquid diet used
      to prevent intestinal obstruction in Cftr-knockout mice had inflammatory
      responses to P. aeruginosa-laden agarose beads similar to those of wild-type mice
      fed an enriched solid diet, so dietary effects are unlikely to account for
      differences between wild-type mice and mice with cystic fibrosis. Finally, since
      cystic fibrosis patients and Cftr-knockout mice have an imbalance in fatty acids
      (significantly lower-than-normal levels of docosahexaenoic acid), the effects of
      specific supplementation with docosahexaenoic acid of wild-type and Cftr-knockout
      mice on their inflammatory responses to P. aeruginosa-laden agarose beads were
      tested. There were no significant differences (P = 0.35) in cumulative survival
      rates between Cftr-knockout mice and wild-type mice provided with either the
      liquid diet Peptamen or Peptamen containing docosahexaenoic acid. In conclusion,
      diet and docosahexaenoic acid imbalances alone are unlikely to explain the
      differences in the host response to lung infections with mucoid P. aeruginosa
      between mice with cystic fibrosis and their wild-type counterparts.

PMID- 14977954
TI  - Nod1 is an essential signal transducer in intestinal epithelial cells infected
      with bacteria that avoid recognition by toll-like receptors.
AB  - The transcription factor NF-kappaB in human intestinal epithelial cells plays a
      central role in regulating genes that govern the onset of mucosal inflammatory
      responses following intestinal microbial infection. Nod1 is a cytosolic pattern
      recognition receptor in mammalian cells that senses components of microbial
      peptidoglycans and signals the activation of NF-kappaB. The aim of these studies
      was to assess the functional importance of Nod1 in activating NF-kappaB and NF
      kappaB proinflammatory target genes in human intestinal epithelium. Human colon
      epithelial cells that constitutively express Nod1 were used as a model intestinal
      epithelium. These cells do not signal through Toll-like receptor 4 (TLR4) or
      respond to bacterial lipopolysaccharide, but they express functional TLR5 and
      interleukin 1 (IL-1) receptors that signal the activation of NF-kappaB in
      response to bacterial flagellin or IL-1 stimulation. Stable expression of
      dominant negative (DN) Nod1 in colon epithelial cells prevented IkappaB kinase
      and NF-kappaB activation in response to infection with enteroinvasive Escherichia
      coli. In contrast, DN Nod1 did not eliminate IL-1 or flagellin-stimulated NF
      kappaB activation. Inhibition of NF-kappaB was accompanied by inhibition of NF
      kappaB target genes that provide signals for the mucosal influx of neutrophils
      during intestinal infection. We conclude that signaling through Nod1 is required
      for activating NF-kappaB in human intestinal epithelial cells infected with gram
      negative enteric bacteria that can bypass TLR activation. Signaling through Nod1
      provides the intestinal epithelium with a backup mechanism for rapidly activating
      innate immunity during infection with a group of highly invasive pathogenic gram
      negative bacteria.

PMID- 14977955
TI  - Evidence for a hybrid genomic island in verocytotoxin-producing Escherichia coli
      CL3 (serotype O113:H21) containing segments of EDL933 (serotype O157:H7) O
      islands 122 and 48.
AB  - Genomic O island 122 (OI-122) of the verocytotoxin-producing Escherichia coli
      (VTEC) strain EDL933 contains four putative virulence genes, Z4321, Z4326, Z4332,
      and Z4333. However, strain CL3 (serotype O113:H21) contains only Z4321, not the
      other three genes. To determine whether Z4321 is part of a different genomic
      island in CL3, a region of 27,293 bp up- and downstream of Z4321 was sequenced
      and found to contain elements of two different EDL933 genomic islands (OI-48 and
      OI-122) and a Yersinia pestis-like hemolysin/adhesin gene cluster. The region
      contained OI-48 genes Z1635, Z1636, and Z1637 at the left terminus and Z1641,
      Z1642, Z1643, and Z1644 at the right. The middle portion consisted of OI-48 gene
      Z1640, which was separated into three fragments by genomic segments including the
      Y. pestis cluster and EDL933 OI-122 genes Z4322, Z4321, and Z4318. In a PCR
      investigation of 36 VTEC strains of different serotypes, intact Z1640 was present
      in strains of serotypes O157:H7, O26:H11, O103:H2, O111:NM, and O145:NM, which
      are associated with hemolytic uremic syndrome and outbreaks. In contrast,
      fragmented Z1640 was seen in strains of nonepidemic serotypes, such as O91:H21
      and O113:H21, and in animal serotypes that have not been associated with human
      disease, indicating that Z1640 might be a virulence gene.

PMID- 14977956
TI  - Gammadelta T cells in immunity induced by Mycobacterium bovis bacillus Calmette
      Guerin vaccination.
AB  - Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccination is efficacious for
      newborns or adults with no previous exposure to environmental mycobacteria. To
      determine the relative contribution and the nature of gammadelta T-cell receptor
      positive T cells in newborns, compared to CD4(+) T cells, in immunity induced by
      M. bovis BCG vaccination, 4-week-old specific-pathogen-free pigs were vaccinated
      with M. bovis BCG and monitored by following the gammadelta T-cell immune
      responses. A flow cytometry-based proliferation assay and intracellular staining
      for gamma interferon (IFN-gamma) were used to examine gammadelta T-cell
      responses. Pigs were found to mount Th1-like responses to M. bovis BCG
      vaccination as determined by immunoproliferation and IFN-gamma production. The
      gammadelta T-cell lymphoproliferation and IFN-gamma production to stimulation
      with mycobacterial antigens were significantly enhanced by M. bovis BCG
      vaccination. The relative number of proliferating gammadelta T cells after
      stimulating peripheral blood mononuclear cells with Mycobacterium tuberculosis
      H37Rv culture filtrate protein was higher than that of CD4(+) T cells at an early
      time point after M. bovis BCG vaccination, but CD4(+) T cells were found to be
      more abundant at a later time point. Although the gammadelta T-cell responses
      were dependent on the presence of CD4(+) T cells for the cytokine interleukin-2,
      the enhanced gammadelta T cells were due to the intrinsic changes of gammadelta T
      cells caused by M. bovis BCG vaccination rather than being due solely to help
      from CD4(+) T cells. Our study shows that gammadelta T cells from pigs at early
      ages are functionally enhanced by M. bovis BCG vaccination and suggests an
      important role for this T-cell subset in acquired immunity conferred by M. bovis
      BCG vaccination.

PMID- 14977957
TI  - Increases in c-Jun N-terminal kinase/stress-activated protein kinase and p38
      activity in monocyte-derived macrophages following the uptake of Legionella
      pneumophila.
AB  - Legionella pneumophila, the causative agent of Legionnaires' disease, infects and
      replicates within a variety of eukaryotic cells. The purpose of the current study
      was to examine host cell signaling events immediately following uptake and early
      in the endocytic process (less than 1 h) following the phagocytosis of L.
      pneumophila. This examination focused on the protein kinase signal pathways to
      identify any aberrant signal(s) induced by L. pneumophila within its host, as a
      means to alter the normal endocytic pathway. The mitogen-activated protein kinase
      cascades are of interest due to their involvement in cellular regulation. The
      experiments were carried out with monocyte-derived macrophages (MDMs). All three
      mitogen-activated protein kinase cascades were activated when MDMs were
      inoculated with either Legionella strain (wild-type strain AA100 or dotA mutant
      GL10) or an Escherichia coli control. Whereas the avirulent treatments, GL10 and
      E. coli, exhibited a leveling off or a return to near basal levels of
      phosphorylation/activity of c-Jun N-terminal kinase by 60 min, the virulent
      strain AA100 exhibited a significantly increased level of activity through 60 min
      that was greater than that seen in GL10 (P = 0.025) and E. coli (P = 0.014). A
      similar trend was seen with p38 phosphorylation. Phosphorylation of mitogen
      activated protein/ERK kinase (MEK) was decreased in strain AA100 compared to E.
      coli. Inhibition of the activity of either the stress-activated protein kinase/c
      Jun N-terminal kinase or p38 pathway significantly decreased the ability of
      legionellae to replicate intracellularly, suggesting the necessity of these two
      pathways in its intracellular survival and replication.

PMID- 14977958
TI  - Helicobacter pylori and complex gangliosides.
AB  - Recognition of sialic acid-containing glycoconjugates by the human gastric
      pathogen Helicobacter pylori has been repeatedly demonstrated. To investigate the
      structural requirements for H. pylori binding to complex gangliosides, a large
      number of gangliosides were isolated and characterized by mass spectrometry and
      proton nuclear magnetic resonance. Ganglioside binding of sialic acid-recognizing
      H. pylori strains (strains J99 and CCUG 17874) and knockout mutant strains with
      the sialic acid binding adhesin SabA or the
      NeuAcalpha3Galbeta4GlcNAcbeta3Galbeta4GlcNAcbeta-binding neutrophil-activating
      protein HPNAP deleted was investigated using the thin-layer chromatogram binding
      assay. The wild-type bacteria bound to N-acetyllactosamine-based gangliosides
      with terminal alpha3-linked NeuAc, while gangliosides with terminal NeuGcalpha3,
      NeuAcalpha6, or NeuAcalpha8NeuAcalpha3 were not recognized. The factors affecting
      binding affinity were identified as (i) the length of the N-acetyllactosamine
      carbohydrate chain, (ii) the branches of the carbohydrate chain, and (iii) fucose
      substitution of the N-acetyllactosamine core chain. While the J99/NAP(-) mutant
      strain displayed a ganglioside binding pattern identical to that of the parent
      J99 wild-type strain, no ganglioside binding was obtained with the J99/SabA(-)
      mutant strain, demonstrating that the SabA adhesin is the sole factor responsible
      for the binding of H. pylori bacterial cells to gangliosides.

PMID- 14977959
TI  - Populations of human T lymphocytes that traverse the vascular endothelium
      stimulated by Borrelia burgdorferi are enriched with cells that secrete gamma
      interferon.
AB  - Some diseases are characterized by prevalence in the affected tissues of type 1 T
      lymphocytes, which secrete gamma interferon (IFN-gamma) and other proinflammatory
      cytokines. For example, type 1 T cells predominate in the lesions of patients
      with Lyme disease, which is caused by the bacterium Borrelia burgdorferi. We used
      an in vitro model of the blood vessel wall to test the premise that the vascular
      endothelium actively recruits circulating type 1 T cells to such lesions. When T
      lymphocytes isolated from human peripheral blood were examined, the populations
      that traversed monolayers of resting human umbilical vein endothelial cells
      (HUVEC) or HUVEC stimulated by interleukin-1beta or B. burgdorferi were markedly
      enriched for T cells that produced IFN-gamma compared to the initially added
      population of T cells. No enrichment was seen for cells that produced interleukin
      4, a marker for type 2 T lymphocytes. Very late antigen-4 and CD11/CD18 integrins
      mediated passage of the T cells across both resting and stimulated HUVEC, and the
      endothelium-derived chemokine CCL2 (monocyte chemoattractant protein 1) was
      responsible for the enhanced migration of T cells across stimulated HUVEC. These
      results suggest that the vascular endothelium may contribute to the selective
      accumulation of type 1 T cells in certain pathological lesions, including those
      of Lyme disease.

PMID- 14977960
TI  - The Burkholderia cepacia epidemic strain marker is part of a novel genomic island
      encoding both virulence and metabolism-associated genes in Burkholderia
      cenocepacia.
AB  - The Burkholderia cepacia epidemic strain marker (BCESM) is a useful
      epidemiological marker for virulent B. cenocepacia strains that infect patients
      with cystic fibrosis. However, there was no evidence that the original marker,
      identified by random amplified polymorphic DNA fingerprinting, contributed to
      pathogenicity. Here we demonstrate that the BCESM is part of a novel genomic
      island encoding genes linked to both virulence and metabolism. The BCESM was
      present on a 31.7-kb low-GC-content island that encoded 35 predicted coding
      sequences (CDSs): an N-acyl homoserine lactone (AHL) synthase gene (cciI) and
      corresponding transcriptional regulator (cciR), representing the first time cell
      signaling genes have been found on a genomic island; fatty acid biosynthesis
      genes; an IS66 family transposase; transcriptional regulator CDSs; amino acid
      metabolism genes; and a group of hypothetical genes. Mutagenesis of the AHL
      synthase, amidase (amiI), and porin (opcI) genes on the island was carried out.
      Testing of the isogenic mutants in a rat model of chronic lung infection
      demonstrated that the amidase played a role in persistence, while the AHL
      synthase and porin were both involved in virulence. The island, designated the B.
      cenocepacia island (cci), is the first genomic island to be defined in the B.
      cepacia complex and its discovery validates the original epidemiological
      correlation of the BCESM with virulent CF strains. The features of the cci, which
      overlap both pathogenicity and metabolism, expand the concept of bacterial
      pathogenicity islands and illustrate the diversity of accessory functions that
      can be acquired by lateral gene transfer in bacteria.

PMID- 14977961
TI  - Epitope mapping of a protective monoclonal antibody against Pneumocystis carinii
      with shared reactivity to Streptococcus pneumoniae surface antigen PspA.
AB  - Pneumocystis carinii is an opportunistic fungal pathogen that causes pneumonia in
      the immunocompromised host. A protective monoclonal antibody (MAb) termed 4F11
      generated against mouse-derived P. carinii was shown by indirect
      immunofluorescence assay (IFA) to bind surface antigens of P. carinii derived
      from multiple host species, including humans. We have identified multiple
      epitopes recognized by MAb 4F11 in two recombinant mouse P. carinii antigens. The
      epitopes mapped have similar proline content and positive charge distribution.
      The consensus 8-mer epitope recognized by MAb 4F11 is K/RPA/RPK/QPA/TP. Immune
      sera raised against intact mouse P. carinii recognized native antigens affinity
      purified with MAb 4F11 and a recombinant antigen reactive with MAb 4F11. Database
      searches for short, nearly exact matches to the mapped MAb 4F11 epitopes
      identified a bacterial surface antigen, Streptococcus pneumoniae PspA, with a
      similar proline-rich region. In an IFA, MAb 4F11 detected antigens on the S.
      pneumoniae surface, and Western blotting identified a protein in S. pneumoniae
      lysates consistent with the M(r) of PspA. A fragment of the S. pneumoniae PspA
      gene was cloned and sequenced, and the deduced amino acid sequence contained a
      region with strong similarity to the MAb 4F11 epitopes identified in P. carinii.
      The PspA recombinant polypeptide was recognized by MAb 4F11 in a Western blot.
      The ability of MAb 4F11 to recognize similar proline-rich epitopes may explain
      its ability to recognize P. carinii derived from multiple hosts and will permit
      testing of the epitopes recognized by this antibody in immunization against P.
      carinii.

PMID- 14977962
TI  - Fine specificity of serum antibodies to Plasmodium falciparum merozoite surface
      protein, PfMSP-1(19), predicts protection from malaria infection and high-density
      parasitemia.
AB  - Antibodies to the C terminus of the Plasmodium falciparum merozoite surface
      protein, PfMSP-1(19), may inhibit merozoite invasion or block the effects of
      inhibitory antibodies. Here, using a competition enzyme-linked immunosorbent
      assay and antibody binding to wild-type and mutated recombinant proteins, we show
      that there are marked variations between individuals in the fine specificity of
      naturally acquired anti-MSP-1(19) antibodies. Furthermore, although neither the
      prevalence nor the concentration of total anti-MSP-1(19) antibodies was
      associated with resistance to malaria in African children, significant
      associations were observed between antibody fine specificity and subsequent risk
      of infection and high-density parasitemia during a follow-up period. Thus, the
      fine specificity of naturally acquired human anti-MSP-1(19) antibodies is crucial
      in determining their function. Future field studies, including the evaluation of
      PfMSP-1 vaccine trials, should include assays that explore antibody fine
      specificity as well as titer.

PMID- 14977963
TI  - Adenylate cyclase toxin from Bordetella pertussis synergizes with
      lipopolysaccharide to promote innate interleukin-10 production and enhances the
      induction of Th2 and regulatory T cells.
AB  - Adenylate cyclase toxin (CyaA) from Bordetella pertussis can subvert host immune
      responses allowing bacterial colonization. Here we have examined its adjuvant and
      immunomodulatory properties and the possible contribution of lipopolysaccharide
      (LPS), known to be present in purified CyaA preparations. CyaA enhanced antigen
      specific interleukin-5 (IL-5) and IL-10 production and immunoglobulin G1
      antibodies to coadministered antigen in vivo. Antigen-specific CD4(+)-T-cell
      clones generated from mice immunized with antigen and CyaA had cytokine profiles
      characteristic of Th2 or type 1 regulatory T (Tr1) cells. Since innate immune
      cells direct the induction of T-cell subtypes, we examined the influence of CyaA
      on activation of dendritic cells (DC) and macrophages. CyaA significantly
      augmented LPS-induced IL-6 and IL-10 and inhibited LPS-driven tumor necrosis
      factor alpha and IL-12p70 production from bone marrow-derived DC and macrophages.
      CyaA also enhanced cell surface expression of CD80, CD86, and major
      histocompatibility class II on immature DC. The stimulatory activity of our CyaA
      preparation for IL-10 production and CD80, CD86, and major histocompatibility
      complex class II expression was attenuated following the addition of polymyxin B
      or with the use of DC from Toll-like receptor (TLR) 4-defective mice. However,
      treatment of DC with LPS alone at the concentration present in the CyaA
      preparation (0.2 ng/ml) failed to activate DC in vitro. Our findings demonstrate
      that activation of innate cells in vitro by CyaA is dependent on a second signal
      through a TLR and that CyaA can promote Th2/Tr1-cell responses by inhibiting IL
      12 and promoting IL-10 production by DC and macrophages.

PMID- 14977964
TI  - Dissolved oxygen levels alter gene expression and antigen profiles in Borrelia
      burgdorferi.
AB  - The Lyme disease spirochete, Borrelia burgdorferi, encounters many environmental
      signals as it cycles between the arthropod vector and mammalian hosts, including
      temperature, pH, and other host factors. To test the possibility that dissolved
      oxygen modulates gene expression in B. burgdorferi, spirochetes were exposed to
      differential levels of dissolved oxygen, and distinct alterations were observed
      at both the transcriptional and translational levels. Specifically NapA, a
      Dps/Dpr homologue involved in the oxidative stress response in other bacteria,
      was reduced when B. burgdorferi was grown under oxygen-limiting conditions. In
      contrast, several immunoreactive proteins were altered when tested with infection
      derived sera from different hosts. Specifically, OspC, DbpA, and VlsE were
      synthesized at greater levels when cells were grown in limiting oxygen, whereas
      VraA was reduced. The levels of oxygen in the medium did not affect OspA
      production. Real-time reverse transcription-PCR analysis of RNA isolated from
      infectious isolates of strains B31 and cN40 indicated that the expression of
      ospC, dbpA, and vlsE increased while napA expression decreased under dissolved
      oxygen-limiting conditions, whereas flaB was not affected. The reverse
      transcription-PCR results corroborated the immunoblot analyses and indicated that
      the increase in OspC, DbpA, and VlsE was due to regulation at the transcriptional
      level of the genes encoding these antigens. These results indicate that dissolved
      oxygen modulates gene expression in B. burgdorferi and imply that the redox
      environment may be an additional regulatory cue that spirochetes exploit to adapt
      to the disparate niches that they occupy in nature.

PMID- 14977965
TI  - A locus contained within a variable region of pneumococcal pathogenicity island 1
      contributes to virulence in mice.
AB  - We have previously described a 27-kb pathogenicity island of Streptococcus
      pneumoniae, termed pneumococcal pathogenicity island 1 (PPI1), which contains
      iron uptake locus piaABCD, required for full virulence in mice, and a further 28
      previously uncharacterized genes. We have investigated one of these, Sp1051,
      which encodes a protein of unknown function. Disruption of Sp1051 does not affect
      growth in laboratory broth, serum, or blood but impairs virulence in mouse models
      of infection. When S. pneumoniae capsular serotypes were analyzed by PCR and
      Southern hybridization, it was found that 33% did not contain Sp1051. Analysis of
      other genes within PPI1 demonstrated that, compared to the serotype 4 genome
      published by The Institute for Genome Research (TIGR), the genomes of many
      strains contain deletions of a variable number of genes between Sp1046 and
      Sp1064, conforming to one of six different patterns. Amplification by PCR of this
      PPI1 variable region from a capsular serotype 17 strain and comparison of the
      sequence to TIGR serotype 4 strain sequence showed that Sp1051 is contained
      within an 11.3-kb segment of DNA flanked by 7-bp direct repeats within the
      serotype 4 strain which is not present in the serotype 17 strain. Further
      comparison of the sequences of this region between the three published S.
      pneumoniae genomes demonstrated that serotype 19F and strain R6 contain novel
      complements of genes not present in the serotype 4 strain. These data indicate
      that there is striking variation in gene content and structure of the 3' region
      of PPI1 among strains and that this region includes at least one virulence
      determinant. Gene variation within horizontally acquired DNA such as that of PPI1
      may be one factor modulating differences in virulence among strains.

PMID- 14977966
TI  - Novel antigen identification method for discovery of protective malaria antigens
      by rapid testing of DNA vaccines encoding exons from the parasite genome.
AB  - We describe a novel approach for identifying target antigens for preerythrocytic
      malaria vaccines. Our strategy is to rapidly test hundreds of DNA vaccines
      encoding exons from the Plasmodium yoelii yoelii genomic sequence. In this
      antigen identification method, we measure reduction in parasite burden in the
      liver after sporozoite challenge in mice. Orthologs of protective P. y. yoelii
      genes can then be identified in the genomic databases of Plasmodium falciparum
      and Plasmodium vivax and investigated as candidate antigens for a human vaccine.
      A pilot study to develop the antigen identification method approach used 192 P.
      y. yoelii exons from genes expressed during the sporozoite stage of the life
      cycle. A total of 182 (94%) exons were successfully cloned into a DNA
      immunization vector with the Gateway cloning technology. To assess immunization
      strategies, mice were vaccinated with 19 of the new DNA plasmids in addition to
      the well-characterized protective plasmid encoding P. y. yoelii circumsporozoite
      protein. Single plasmid immunization by gene gun identified a novel vaccine
      target antigen which decreased liver parasite burden by 95% and which has
      orthologs in P. vivax and P. knowlesi but not P. falciparum. Intramuscular
      injection of DNA plasmids produced a different pattern of protective responses
      from those seen with gene gun immunization. Intramuscular immunization with
      plasmid pools could reduce liver parasite burden in mice despite the fact that
      none of the plasmids was protective when given individually. We conclude that
      high-throughput cloning of exons into DNA vaccines and their screening is
      feasible and can rapidly identify new malaria vaccine candidate antigens.

PMID- 14977967
TI  - Antibodies that inhibit binding of Plasmodium falciparum-infected erythrocytes to
      chondroitin sulfate A and to the C terminus of merozoite surface protein 1
      correlate with reduced placental malaria in Cameroonian women.
AB  - Plasmodium falciparum-infected erythrocytes often sequester in the placenta of
      pregnant women, producing placental malaria, a condition that can compromise the
      health of the developing fetus. Scientists are hopeful that a vaccine can be
      developed to prevent this condition. Immunological mechanisms responsible for
      eliminating parasites from the placenta remain unclear, but antibodies to the
      carboxyl-terminal 19-kDa segment of the merozoite surface protein 1 (MSP1-19),
      the ring-infected erythrocyte surface antigen (RESA), and an erythrocyte-surface
      ligand that binds chondroitin sulfate A (CSA-L) have been implicated. In
      addition, antibodies to sporozoite and liver-stage antigens could reduce initial
      parasite burdens. This study sought to determine if antibodies to the
      circumsporozoite protein (CSP), liver-stage antigen 1 (LSA1), RESA, MSP1-19, or
      CSA-L correlated with either the absence of placental parasites or low placental
      parasitemias. Using a frequency-matched case-control study design, we compared
      antibody levels in women (gravidity 1 to 11) with and without placental malaria.
      Results showed that women who were antibody negative for MSP1-19 were at a higher
      risk of having placental malaria than women with antibodies (P < 0.007).
      Furthermore, an association between high levels of antibodies that blocked the
      binding of infected erythrocytes to CSA and low placental parasitemias was
      observed (P = 0.02). On the other hand, women with high antibody levels at term
      to CSP, LSA1, and RESA were more likely to have placental malaria than antibody
      negative women. Since antibodies to MSP1-19 and CSA-L were associated with
      reduced placental malaria, both antigens show promise for inclusion in a vaccine
      for women of child-bearing age.

PMID- 14977968
TI  - Combination of the cationic surfactant dimethyl dioctadecyl ammonium bromide and
      synthetic mycobacterial cord factor as an efficient adjuvant for tuberculosis
      subunit vaccines.
AB  - Recombinant, immunodominant antigens derived from Mycobacterium tuberculosis can
      be used to effectively vaccinate against subsequent infection. However, the
      efficacy of these recombinant proteins is dependent on the adjuvant used for
      their delivery. This problem affects many potential vaccines, not just those for
      tuberculosis, so the discovery of adjuvants that can promote the development of
      cell-mediated immunity is of great interest. We have previously shown that the
      combination of the cationic surfactant dimethyl dioctadecyl ammonium bromide and
      the immunomodulator modified lipid A synergistically potentiates Th1 T-cell
      responses. Here we report a screening program for other adjuvants with reported
      Th1-promoting activity and identify a second novel adjuvant formulation that
      drives the development of Th1 responses with an extremely high efficacy. The
      combination of dimethyl dioctadecyl ammonium bromide and the synthetic cord
      factor trehalose dibehenate promotes strong protective immune responses, without
      overt toxicity, against M. tuberculosis infection in a vaccination model and thus
      appears to be a very promising candidate for the development of human vaccines.

PMID- 14977969
TI  - Role for serine protease HtrA (DegP) of Streptococcus pyogenes in the biogenesis
      of virulence factors SpeB and the hemolysin streptolysin S.
AB  - The serine protease HtrA is involved in the folding and maturation of secreted
      proteins, as well as in the degradation of proteins that misfold during
      secretion. Depletion of HtrA has been shown to affect the sensitivity of many
      organisms to thermal and environmental stresses, as well as being essential for
      virulence in many pathogens. In the present study, we compared the behaviors of
      several different HtrA mutants of the gram-positive pathogen Streptococcus
      pyogenes (group A streptococcus). Consistent with prior reports, insertional
      inactivation of htrA, the gene that encodes HtrA, resulted in a mutant that grew
      poorly at 37 degrees C. However, an identical phenotype was observed when a
      similar polar insertion was placed immediately downstream of htrA in the
      streptococcal chromosome, suggesting that the growth defect of the insertion
      mutant was not a direct result of insertional inactivation of htrA. This
      conclusion was supported by the observation that a nonpolar deletion mutation of
      htrA did not produce the growth defect. However, this mutation did affect the
      production of several secreted virulence factors whose biogenesis requires
      extensive processing. For the SpeB cysteine protease, the loss of HtrA was
      associated with a failure to proteolytically process the zymogen to an active
      protease. For the streptolysin S hemolysin, a dramatic increase in hemolytic
      activity resulted from the depletion of HtrA. Interestingly, HtrA-deficient
      mutants were not attenuated in a murine model of subcutaneous infection. These
      data add to the growing body of information that implies an important role for
      HtrA in the biogenesis of secreted proteins in gram-positive bacteria.

PMID- 14977970
TI  - Mycobacterium-inducible Nramp in striped bass (Morone saxatilis).
AB  - In mammals, the natural resistance-associated macrophage protein 1 gene, Nramp1,
      plays a major role in resistance to mycobacterial infections. Chesapeake Bay
      striped bass (Morone saxatilis) is currently experiencing an epizootic of
      mycobacteriosis that threatens the health of this ecologically and economically
      important species. In the present study, we characterized an Nramp gene in this
      species and obtained evidence that there is induction following Mycobacterium
      exposure. The striped bass Nramp gene (MsNramp) and a 554-amino-acid sequence
      contain all the signal features of the Nramp family, including a topology of 12
      transmembrane domains (TM), the transport protein-specific binding-protein
      dependent transport system inner membrane component signature, three N-linked
      glycosylation sites between TM 7 and TM 8, sites of casein kinase and protein
      kinase C phosphorylation in the amino and carboxy termini, and a tyrosine kinase
      phosphorylation site between TM 6 and TM 7. Phylogenetic analysis most closely
      grouped MsNramp with other teleost Nramp genes and revealed high sequence
      similarity with mammalian Nramp2. MsNramp expression was present in all tissues
      assayed by reverse transcription-PCR. Within 1 day of injection of Mycobacterium
      marinum, MsNramp expression was highly induced (17-fold higher) in peritoneal
      exudate (PE) cells compared to the expression in controls. The levels of MsNramp
      were three- and sixfold higher on days 3 and 15, respectively. Injection of
      Mycobacterium shottsii resulted in two-, five-, and threefold increases in gene
      expression in PE cells over the time course. This report is the first report of
      induction of an Nramp gene by mycobacteria in a poikilothermic vertebrate.

PMID- 14977971
TI  - Blockade of endogenous leukotrienes exacerbates pulmonary histoplasmosis.
AB  - Leukotrienes are classical mediators of inflammatory response. New aspects of
      leukotriene function have recently been described. We examine here the previously
      unreported role that leukotrienes play in the regulation of cytokines in a murine
      model of histoplasmosis. We demonstrate that administration of MK 886, a
      leukotriene synthesis inhibitor, caused Histoplasma capsulatum-infected mice to
      die by the day 15 of infection, whereas the correlating death rate in untreated
      infected mice was 0%. Treating infected animals with MK 886 inhibited leukotriene
      synthesis but increased leukocyte recruitment to the lungs. Subsequent to this
      phenomenon, levels of tumor necrosis factor alpha, interleukin-1 (IL-1), IL-6,
      and KC chemoattractant cytokines and fungi in the lung parenchyma increased, as
      did inflammatory response. In contrast, IL-2, IL-5, IL-12, and gamma interferon
      cytokine levels actually decreased. Thus, murine response to pulmonary
      histoplasmosis may be leukotriene modulated. This finding may enable us to alter
      the course of the immune response and inflammation caused by histoplasmosis. The
      data from the present study suggest an important new strategy for immunologic or
      drug intervention in human patients.

PMID- 14977972
TI  - Characterization of oral Yersinia enterocolitica infection in three different
      strains of inbred mice.
AB  - Several studies have highlighted differences in the resistances of various mouse
      strains to intravenous (i.v.) infection with Yersinia enterocolitica. In
      particular, differences in resistance and immunological response between BALB/c
      and C57BL/6 mouse strains have been determined. Following i.v infection, C57BL/6
      mice are more resistant to Y. enterocolitica than are BALB/c mice. However,
      because Y. enterocolitica is typically a food-borne pathogen, the oral route of
      infection more accurately reflects the natural route of infection. Therefore, it
      was of interest to ascertain if the differences in resistance between mouse
      strains observed for an i.v. infection can be recapitulated following an oral
      infection. C57BL/6j, BALB/cj, and 129X1/Svj mouse strains presented no
      differences in 50% lethal dose (LD(50)) following oral infection with Y.
      enterocolitica. Subsequent analysis of cytokine levels, bacterial colonization
      and immune cell populations following oral infection confirmed characteristics
      previously described following i.v. Y. enterocolitica infection. All tissues
      analyzed from each mouse strain demonstrated a polarized Th1 cytokine profile and
      inflammatory cell influx throughout a 7-day course of infection. This immune
      response was present in all tissues and increased as bacterial colonization
      progressed. The lack of a differing LD(50) phenotype and common trends in
      immunological response among the three mouse strains tested suggests that oral
      infection is a useful model for studying the host response to Y. enterocolitica
      infection.

PMID- 14977973
TI  - Relationship between structures and biological activities of mycoplasmal
      diacylated lipopeptides and their recognition by toll-like receptors 2 and 6.
AB  - The lipopeptide FSL-1 [S-(2,3-bispalmitoyloxypropyl)-Cys-Gly-Asp-Pro-Lys-His-Pro
      Lys-Ser-Phe, Pam(2)CGDPKHPKSF] synthesized on the basis of the N-terminal
      structure of a Mycoplasma salivarium lipoprotein capable of activating normal
      human gingival fibroblasts to induce the cell surface expression of ICAM-1
      revealed an activity to induce production of monocyte chemoattractant protein 1,
      interleukin-6 (IL-6), and IL-8. FSL-1 also activated macrophages to produce tumor
      necrosis factor alpha as the Mycoplasma fermentans-derived lipopeptide MALP-2
      (Pam(2)CGNNDESNISFKEK), a potent macrophage-activating lipopeptide, did. The
      level of the activity of FSL-1 was higher than that of MALP-2. This result
      suggests that the difference in the amino acid sequence of the peptide portion
      affects the activity because the framework structure other than the amino acid
      sequence of the former is the same as that of the latter. To determine minimal
      structural requirements for the activity of FSL-1, the diacylglyceryl Cys and the
      peptide portions were examined for this activity. Both portions did not reveal
      the activity. A single amino acid substitution from Phe to Arg and a fatty acid
      substitution from palmitic acid to stearic acid drastically reduced the activity.
      Similar results were obtained in measuring the NF-kappaB reporter activity of FSL
      1 to human embryonic kidney 293 cells transfected with Toll-like receptor 2 and
      6, together with a NF-kappaB-dependent luciferase reporter plasmid. These results
      suggest that both the diacylglyceryl and the peptide portions of FSL-1 are
      indispensable for the expression of biological activities and for the recognition
      by Toll-like receptors 2 and 6 and that the recognition of FSL-1 by Toll-like
      receptors 2 and 6 appears to be hydrophobic.

PMID- 14977974
TI  - Glycolytic and gluconeogenic growth of Escherichia coli O157:H7 (EDL933) and E.
      coli K-12 (MG1655) in the mouse intestine.
AB  - Escherichia coli EDL933, an O157:H7 strain, is known to colonize the streptomycin
      treated CD-1 mouse intestine by growing in intestinal mucus (E. A. Wadolkowski,
      J. A. Burris, and A. D. O'Brien, Infect. Immun. 58:2438-2445, 1990), but what
      nutrients and metabolic pathways are employed during colonization has not been
      determined. In this study, when the wild-type EDL933 strain was fed to mice along
      with an EDL933 DeltappsA DeltapckA mutant, which is unable to utilize
      tricarboxylic acid cycle intermediates and gluconeogenic substrates for growth,
      both strains colonized the mouse intestine equally well. Therefore, EDL933
      utilizes a glycolytic substrate(s) for both initial growth and maintenance when
      it is the only E. coli strain fed to the mice. However, in the presence of large
      numbers of MG1655, a K-12 strain, it is shown that EDL933 utilizes a glycolytic
      substrate(s) for initial growth in the mouse intestine but appears to utilize
      both glycolytic and gluconeogenic substrates in an attempt to maintain
      colonization. It is further shown that MG1655 predominantly utilizes glycolytic
      substrates for growth in the mouse intestine whether growing in the presence or
      absence of large numbers of EDL933. Data are presented showing that although
      small numbers of EDL933 grow to large numbers in the intestine in the presence of
      large numbers of MG1655 when both strains are fed to mice simultaneously,
      precolonization with MG1655 affords protection against subsequent colonization by
      EDL933. Moreover, in mice that are precolonized with EDL933, small numbers of
      MG1655 are able to grow rapidly in the intestine and EDL933 is eliminated. In
      situ hybridization experiments using E. coli-specific rRNA probes showed that
      while MG1655 is found only in mucus, EDL933 is found both in mucus and closely
      associated with intestinal epithelial cells. The data are discussed with respect
      to competition for nutrients and to the protection that some intestinal commensal
      E. coli strains might afford against infection by O157:H7 strains.

PMID- 14977975
TI  - An adenylate cyclase-controlled signaling network regulates Pseudomonas
      aeruginosa virulence in a mouse model of acute pneumonia.
AB  - Infections caused by the opportunistic pathogen Pseudomonas aeruginosa involve
      the interplay of several bacterial virulence factors. It has recently been
      established that the delivery of toxic effector proteins by the type III
      secretion system is an important virulence mechanism in several animal models.
      Furthermore, the expression of the type III secretion system and its effectors
      has been correlated with a poor clinical outcome during human infections. A novel
      cyclic AMP (cAMP) regulatory network that controls the expression of virulence
      factors, including the type III secretion system, was examined to determine its
      contribution to P. aeruginosa colonization and dissemination in a mouse pneumonia
      model. Mutants lacking the two genome-encoded adenylate cyclases, CyaA and CyaB,
      and the cAMP-dependent regulator Vfr were examined. Based on the enumeration of
      bacteria in lungs, livers, and spleens, as well as the assessment of mouse lung
      pathology, mutations in the cyaB and vfr genes resulted in a more significantly
      attenuated phenotype than mutations in cyaA. Moreover, in this model, expression
      of the type III secretion system was essential for lung colonization and
      pathology. Strains with mutations in the exsA gene, which encodes a type III
      regulatory protein, or pscC, which encodes an essential component of the
      secretion apparatus, were also significantly attenuated. Finally, we demonstrate
      that virulence can be restored in an adenylate cyclase mutant by the
      overexpression of exsA, which specifically restores expression of the type III
      secretion system in the absence of a functional cAMP-dependent regulatory
      network.

PMID- 14977976
TI  - Immunization with a DNA vaccine cocktail protects mice lacking CD4 cells against
      an aerogenic infection with Mycobacterium tuberculosis.
AB  - Tuberculosis (TB) is the most common opportunistic disease and a potentially
      fatal complication among immunocompromised individuals infected with human
      immunodeficiency virus (HIV). Effective vaccination against TB in persons with
      HIV has been considered unlikely because of the central role that CD4 cells play
      in controlling tuberculous infections. Here we show that the vaccination of CD8(
      /-) mice with a TB DNA vaccine cocktail did not significantly enhance protective
      responses to a Mycobacterium tuberculosis infection. In contrast, immunization
      with a DNA vaccine cocktail or with the current TB vaccine, Mycobacterium bovis
      BCG, induced considerable antituberculosis protective immunity in immune
      deficient mice lacking CD4 cells. In vaccinated CD4(-/-) animals, substantially
      reduced bacterial burdens in organs and much improved lung pathology were seen 1
      month after an aerogenic M. tuberculosis challenge. Importantly, the
      postchallenge mean times to death of vaccinated CD4(-/-) mice were significantly
      extended (mean with DNA cocktail, 172 +/- 7 days; mean with BCG, 156 +/- 22 days)
      compared to that of naive CD4(-/-) mice (33 +/- 6 days). Furthermore, the
      treatment of DNA-vaccinated CD4(-/-) mice with an anti-CD8 or anti-gamma
      interferon (IFN-gamma) antibody significantly reduced the effect of immunization,
      and neither IFN-gamma(-/-) nor tumor necrosis factor receptor-deficient mice were
      protected by DNA immunization; therefore, the primary vaccine-induced protective
      mechanism in these immune-deficient mice likely involves the secretion of
      cytokines from activated CD8 cells. The substantial CD8-mediated protective
      immunity that was generated in the absence of CD4 cells suggests that it may be
      possible to develop effective TB vaccines for use in HIV-infected populations.

PMID- 14977977
TI  - CNLAC1 is required for extrapulmonary dissemination of Cryptococcus neoformans
      but not pulmonary persistence.
AB  - The pathogenic yeast Cryptococcus neoformans produces a laccase enzyme (CNLAC1),
      which catalyzes the synthesis of melanin in the presence of phenolic compounds. A
      number of genes have been implicated in the regulation of laccase and
      melanization, including IPC1, GPA1, MET3, and STE12. Albino mutants derived from
      random mutagenesis techniques may contain mutations in genes that regulate
      multiple virulence factors, including CNLAC1. The goal of our study is to
      investigate the role of CNLAC1 in virulence and evasion of pulmonary host
      defenses after infection via the respiratory tract. Using a set of congenic
      laccase-positive (2E-TUC-4) and laccase-deficient (2E-TU-4) strains, we found
      that both strains are avirulent at a lower dose (10(4) CFU/mouse) in mice. After
      the infectious dose was increased to 10(6) CFU/mouse, 70% mortality was observed
      in mice infected with 2E-TUC-4 compared to no mortality in mice infected with 2E
      TU-4 at day 30 postinfection. This observation confirms the requirement for
      CNLAC1 in virulence. Interestingly, we observed no differences between the two
      strains in pulmonary growth or in elicitation of cellular immune responses in the
      lung. The only measurable defect of 2E-TU-4 was in dissemination to
      extrapulmonary sites. To examine the role of CNLAC1 in dissemination, mice were
      infected intravenously. By week 3 postinfection, equal numbers of strains 2E-TUC
      4 and 2E-TU-4 were recovered from the brain and spleen. This observation
      indicates that CNLAC1 facilitates escape from the lung, but not growth in the
      lungs or brain, and suggests a novel role for CNLAC1 in virulence during an
      infection aquired via the respiratory tract.

PMID- 14977978
TI  - Susceptibility to tuberculosis: clues from studies with inbred and outbred New
      Zealand White rabbits.
AB  - The rabbit model of tuberculosis (TB) is important because rabbits develop a
      disease that is similar to TB in humans, namely, granulomas with caseous
      necrosis, liquefaction, and cavities. We describe here a comparison of inbred and
      outbred New Zealand White rabbits infected by aerosol with either Mycobacterium
      tuberculosis Erdman or H37Rv strain. Five weeks after infection with either
      bacillary strain, the inbred rabbits had significantly larger pulmonary tubercles
      than did outbred rabbits (2.7 versus 1.4 mm in diameter; P < 0.01). After
      infection with H37Rv, the inbred rabbits had significantly more pulmonary
      tubercles than did the outbred rabbits (98 +/- 12 versus 33 +/- 13; P < 0.01),
      with more mycobacterial CFU per tubercle (809 +/- 210 versus 215 +/- 115; P =
      0.027) (means +/- standard errors of the means). Compared with histologic
      examination of lung granulomas from outbred rabbits, histologic examination of
      those from inbred rabbits showed more caseous necrosis, more visible bacilli, and
      fewer mature epithelioid cells. The delayed-type hypersensitivity (DTH) responses
      to intradermal tuberculin were significantly lower, and peritoneal macrophages
      from uninfected inbred rabbits produced significantly less tumor necrosis factor
      alpha after lipopolysaccharide (LPS) stimulation in vitro than those from the
      outbred rabbits (2,413 +/- 1,154 versus 8,879 +/- 966 pg/ml). We conclude that
      these inbred rabbits were more susceptible to TB than their outbred counterparts
      and had an impaired ability to contain disease, resulting in more grossly visible
      tubercles that were larger than those observed in outbred rabbits. Preliminary
      evidence is presented for a cell-mediated immune defect with lower DTH responses
      and macrophages that have a decreased ability to respond to in vitro stimulation
      with LPS or M. tuberculosis infection.

PMID- 14977979
TI  - Porphyromonas gingivalis induces receptor activator of NF-kappaB ligand
      expression in osteoblasts through the activator protein 1 pathway.
AB  - Porphyromonas gingivalis, an important periodontal pathogen, is closely
      associated with inflammatory alveolar bone resorption, and several components of
      the organism such as lipopolysaccharides have been reported to stimulate
      production of cytokines that promote inflammatory bone destruction. We
      investigated the effect of infection with viable P. gingivalis on cytokine
      production by osteoblasts. Reverse transcription-PCR and real-time PCR analyses
      revealed that infection with P. gingivalis induced receptor activator of nuclear
      factor kappaB (NF-kappaB) ligand (RANKL) mRNA expression in mouse primary
      osteoblasts. Production of interleukin-6 was also stimulated; however,
      osteoprotegerin was not. SB20350 (an inhibitor of p38 mitogen-activated protein
      kinase), PD98059 (an inhibitor of classic mitogen-activated protein kinase
      kinase, MEK1/2), wortmannin (an inhibitor of phosphatidylinositol 3 kinase), and
      carbobenzoxyl-leucinyl-leucinyl-leucinal (an inhibitor of NF-kappaB) did not
      prevent the RANKL expression induced by P. gingivalis. Degradation of inhibitor
      of NF-kappaB-alpha was not detectable; however, curcumin, an inhibitor of
      activator protein 1 (AP-1), prevented the RANKL production induced by P.
      gingivalis infection. Western blot analysis revealed that phosphorylation of c
      Jun, a component of AP-1, occurred in the infected cells, and an analysis of c
      Fos binding to an oligonucleotide containing an AP-1 consensus site also
      demonstrated AP-1 activation in infected osteoblasts. Infection with P.
      gingivalis KDP136, an isogenic deficient mutant of arginine- and lysine-specific
      cysteine proteinases, did not stimulate RANKL production. These results suggest
      that P. gingivalis infection induces RANKL expression in osteoblasts through AP-1
      signaling pathways and cysteine proteases of the organism are involved in RANKL
      production.

PMID- 14977980
TI  - Conservation and diversity of sap homologues and their organization among
      Campylobacter fetus isolates.
AB  - Campylobacter fetus surface layer proteins (SLPs), encoded by sapA homologues,
      are important in virulence. In wild-type C. fetus strain 23D, all eight sapA
      homologues are located in the 54-kb sap island, and SLP expression reflects the
      position of a unique sapA promoter in relation to the sapA homologues. The
      extensive homologies in the sap island include both direct and inverted repeats,
      which allow DNA rearrangements, deletion, or duplication; these elements confer
      substantial potential for genomic plasticity. To better understand C. fetus sap
      island diversity and variation mechanisms, we investigated the organization and
      distribution of sapA homologues among 18 C. fetus strains of different
      subspecies, serotypes, and origins. For all type A strains, the boundaries of the
      sap island were relatively consistent. A 187-bp noncoding DNA insertion near the
      upstream boundary of the sap island was found in two of three reptile strains
      studied. The sapA homologue profiles were strain specific, and six new sapA
      homologues were recognized. Several homologues from reptile strains are
      remarkably conserved in relation to their corresponding mammalian homologues. In
      total, the observed differences suggest that the sap island has evolved differing
      genotypes that are plastic, perhaps enabling colonization of varied niches, in
      addition to antigenic variation.

PMID- 14977981
TI  - Fimbriated Porphyromonas gingivalis is more efficient than fimbria-deficient P.
      gingivalis in entering human dendritic cells in vitro and induces an inflammatory
      Th1 effector response.
AB  - Porphyromonas gingivalis is a fimbriated mucosal pathogen implicated in chronic
      periodontitis (CP). The fimbriae are required for invasion of the gingival mucosa
      and for induction of CP in animal models of periodontitis. CP is associated with
      infection of immature dendritic cells (DCs) by P. gingivalis in situ and with
      increased numbers of dermal DCs (DDCs) and mature DCs in the lamina propria. The
      role of fimbriae in gaining entry into human DCs and how this modulates the
      inflammatory and effector immune responses, however, have not been explored. To
      address this, we generated monocyte-derived DCs (MDDCs) in vitro which
      phenotypically and functionally resemble DDCs. We show here that virulent
      fimbriated P. gingivalis 381, in contrast to its fimbria-deficient mutant, P.
      gingivalis DPG3, efficiently gains entry to MDDCs in a manner dependent on active
      cell metabolism and cytoskeletal rearrangement. In addition, uptake of 381,
      unlike DPG3, induces DCs to undergo maturation, upregulate costimulatory
      molecules, and secrete inflammation cytokines interleukin-1beta (IL-1beta), IL-6,
      tumor necrosis factor alpha, IL-10, and IL-12. Moreover, MDDCs pulsed with 381
      also stimulated a higher autologous mixed lymphocyte reaction and induced a Th1
      type response, with gamma interferon (IFN-gamma) being the main cytokine.
      Monocytes used as controls demonstrated fimbria-dependent uptake of 381 as well
      but produced low levels of inflammatory cytokines compared to MDDCs. When MDDCs
      were pulsed with recombinant fimbrillin of P. gingivalis (10 micro g/ml),
      maturation of MDDCs was also induced; moreover, matured MDDCs induced
      proliferation of autologous CD4(+) T cells and release of IFN-gamma. Thus, these
      results establish the significance of P. gingivalis fimbriae in the uptake of P.
      gingivalis by MDDCs and in induction of immunostimulatory Th1 responses.

PMID- 14977982
TI  - Attenuation of late-stage disease in mice infected by the Mycobacterium
      tuberculosis mutant lacking the SigF alternate sigma factor and identification of
      SigF-dependent genes by microarray analysis.
AB  - The Mycobacterium tuberculosis alternate sigma factor, SigF, is expressed during
      stationary growth phase and under stress conditions in vitro. To better
      understand the function of SigF we studied the phenotype of the M. tuberculosis
      DeltasigF mutant in vivo during mouse infection, tested the mutant as a vaccine
      in rabbits, and evaluated the mutant's microarray expression profile in
      comparison with the wild type. In mice the growth rates of the DeltasigF mutant
      and wild-type strains were nearly identical during the first 8 weeks after
      infection. At 8 weeks, the DeltasigF mutant persisted in the lung, while the wild
      type continued growing through 20 weeks. Histopathological analysis showed that
      both wild-type and mutant strains had similar degrees of interstitial and
      granulomatous inflammation during the first 12 weeks of infection. However, from
      12 to 20 weeks the mutant strain showed smaller and fewer lesions and less
      inflammation in the lungs and spleen. Intradermal vaccination of rabbits with the
      M. tuberculosis DeltasigF strain, followed by aerosol challenge, resulted in
      fewer tubercles than did intradermal M. bovis BCG vaccination. Complete genomic
      microarray analysis revealed that 187 genes were relatively underexpressed in the
      absence of SigF in early stationary phase, 277 in late stationary phase, and only
      38 genes in exponential growth phase. Numerous regulatory genes and those
      involved in cell envelope synthesis were down-regulated in the absence of SigF;
      moreover, the DeltasigF mutant strain lacked neutral red staining, suggesting a
      reduction in the expression of envelope-associated sulfolipids. Examination of 5'
      untranslated sequences among the downregulated genes revealed multiple instances
      of a putative SigF consensus recognition sequence: GGTTTCX(18)GGGTAT. These
      results indicate that in the mouse the M. tuberculosis DeltasigF mutant strain
      persists in the lung but at lower bacterial burdens than wild type and is
      attenuated by histopathologic assessment. Microarray analysis has identified SigF
      dependent genes and a putative SigF consensus recognition site.

PMID- 14977983
TI  - Protective efficacy of antigenic fractions in mouse models of cryptococcosis.
AB  - Infections due to the encapsulated fungus Cryptococcus neoformans are a
      significant cause of morbidity and mortality in patients with impaired T-cell
      function, particularly those with AIDS. Presumably then, T-cell responses to
      cryptococcal antigens are critical for protection against this ubiquitous fungus.
      To test the protective efficacy of these antigens as vaccine candidates, secreted
      cryptococcal antigens were separated by concanavalin A affinity chromatography
      into adherent (mannoprotein [MP]) and nonadherent (flowthrough [FT]) fractions,
      and the fractions were tested in murine models of disseminated cryptococcosis.
      Compared with adjuvant alone, C57BL/6 mice that received two inoculations of MP
      and FT exhibited prolonged survival and reduced brain and kidney fungal loads
      following intravenous challenge with C. neoformans strain B3501. MP-immunized
      animals had increased brain levels of tumor necrosis factor alpha, gamma
      interferon, and interleukin-2. Histopathologic examination revealed that compared
      with organs from mice that received only adjuvant, MP-immunized mice were able to
      recruit a stronger cellular infiltrate in brain, kidney, and liver in response to
      cryptococcal infection. Conjugated O-linked glycans were necessary for optimal MP
      mediated protection, because chemical O deglycosylation reduced the protective
      efficacy of MP immunization. FT and MP immunization protected B-cell-deficient,
      but not T-cell-deficient mice, suggesting that protection was T-cell mediated.
      CBA/J mice also benefited from immunization with FT and MP, although the benefits
      were more modest than those seen with C57BL/6 mice. Thus, both MP and FT
      fractions of C. neoformans contain components that protect mice from disseminated
      cryptococcosis, and this protection appears to be T-cell mediated.

PMID- 14977984
TI  - OspB antibody prevents Borrelia burgdorferi colonization of Ixodes scapularis.
AB  - Borrelia burgdorferi outer surface protein OspB is expressed by spirochetes in
      the Ixodes scapularis gut. ospB is transcribed from a bicistronic operon with
      ospA, a known spirochete adhesion gene in the tick gut. Here we examine whether
      OspB also has a specific function in ticks. OspB specifically binds to a protein
      or protein complex within the tick gut. We also assessed whether selected
      nonborreliacidal OspB antibodies or F(ab)(2) fragments interfere with B.
      burgdorferi-tick attachment in vivo. We examined engorged ticks that fed on B.
      burgdorferi N40-infected scid mice that had been treated with OspB F(ab)(2)
      fragments. Control F(ab)(2) fragments did not interfere with B. burgdorferi
      colonization of the tick gut, whereas OspB F(ab)(2) fragments significantly
      inhibited the attachment of spirochetes to the tick gut. These studies show that
      nonbactericidal OspB antibodies interfere with B. burgdorferi colonization of I.
      scapularis, highlighting a specific role for OspB in spirochete- arthropod
      interactions and suggesting new antibody-mediated strategies for interfering with
      B. burgdorferi transmission.

PMID- 14977985
TI  - Fusarium oxysporum as a multihost model for the genetic dissection of fungal
      virulence in plants and mammals.
AB  - Fungal pathogens cause disease in plant and animal hosts. The extent to which
      infection mechanisms are conserved between both classes of hosts is unknown. We
      present a dual plant-animal infection system based on a single strain of Fusarium
      oxysporum, the causal agent of vascular wilt disease in plants and an emerging
      opportunistic human pathogen. Injection of microconidia of a well-characterized
      tomato pathogenic isolate (isolate 4287) into the lateral tail vein of
      immunodepressed mice resulted in disseminated infection of multiple organs and
      death of the animals. Knockout mutants in genes encoding a mitogen-activated
      protein kinase, a pH response transcription factor, or a class V chitin synthase
      previously shown to be implicated in virulence on tomato plants were tested in
      the mouse model. The results indicate that some of these virulence factors play
      functionally distinct roles during the infection of tomato plants and mice. Thus,
      a single F. oxysporum strain can be used to study fungal virulence mechanisms in
      plant and mammalian pathogenesis.

PMID- 14977986
TI  - C3 promotes clearance of Klebsiella pneumoniae by A549 epithelial cells.
AB  - The airway epithelium represents a primary site for contact between microbes and
      their hosts. To assess the role of complement in this event, we studied the
      interaction between the A549 cell line derived from human alveolar epithelial
      cells and a major nosocomial pathogen, Klebsiella pneumoniae, in the presence of
      serum. In vitro, we found that C3 opsonization of poorly encapsulated K.
      pneumoniae clinical isolates and an unencapsulated mutant enhanced dramatically
      bacterial internalization by A549 epithelial cells compared to highly
      encapsulated clinical isolates. Local complement components (either present in
      the human bronchoalveolar lavage or produced by A549 epithelial cells) were
      sufficient to opsonize K. pneumoniae. CD46 could competitively inhibit the
      internalization of K. pneumoniae by the epithelial cells, suggesting that CD46 is
      a receptor for the binding of complement-opsonized K. pneumoniae to these cells.
      We observed that poorly encapsulated strains appeared into the alveolar
      epithelial cells in vivo but that (by contrast) they were completely avirulent in
      a mouse model of pneumonia compared to the highly encapsulated strains. Our
      results show that bacterial opsonization by complement enhances the
      internalization of the avirulent microorganisms by nonphagocytic cells such as
      A549 epithelial cells and allows an efficient innate defense.

PMID- 14977987
TI  - Determination of surface-exposed, functional domains of gonococcal transferrin
      binding protein A.
AB  - The gonococcal transferrin receptor is composed of two distinct proteins, TbpA
      and TbpB. TbpA is a member of the TonB-dependent family of integral outer
      membrane transporters, while TbpB is lipid modified and thought to be
      peripherally surface exposed. We previously proposed a hypothetical topology
      model for gonococcal TbpA that was based upon computer predictions and similarity
      with other TonB-dependent transporters for which crystal structures have been
      determined. In the present study, the hemagglutinin epitope was inserted into
      TbpA to probe the surface topology of this protein and secondarily to test the
      functional impacts of site-specific mutagenesis. Twelve epitope insertion mutants
      were constructed, five of which allowed us to confirm the surface exposure of
      loops 2, 3, 5, 7, and 10. In contrast to the predictions set forth by the
      hypothetical model, insertion into the plug region resulted in an epitope that
      was surface accessible, while epitope insertions into two putative loops (9 and
      11) were not surface accessible. Insertions into putative loop 3 and beta strand
      9 abolished transferrin binding and utilization, and the plug insertion mutant
      exhibited decreased transferrin-binding affinity concomitant with an inability to
      utilize it. Insertion into putative beta strand 16 generated a mutant that was
      able to bind transferrin normally but that was unable to mediate utilization.
      Mutants with insertions into putative loops 2, 9, and 11 maintained wild-type
      binding affinity but could utilize only transferrin in the presence of TbpB. This
      is the first demonstration of the ability of TbpB to compensate for a mutation in
      TbpA.

PMID- 14977988
TI  - Identification and molecular characterization of EatA, an autotransporter protein
      of enterotoxigenic Escherichia coli.
AB  - Enterotoxigenic Escherichia coli (ETEC) strains remain a formidable cause of
      diarrheal disease. To identify novel surface proteins of ETEC, we performed
      TnphoA mutagenesis of prototype ETEC strain H10407 and discovered a secreted
      protein not previously recognized in ETEC. DNA sequencing of the interrupted
      locus in mutant TnphoA.977 revealed a candidate 4,095-bp open reading frame
      without significant homology to commensal E. coli K-12 genomic DNA. Translation
      of this sequence revealed that it encoded a predicted peptide of 147.7 kDa that
      bears significant homology to members of the autotransporter family of bacterial
      virulence factors, particularly the serine protease autotransporters of the
      Enterobacteriaceae proteins. The gene identified in H10407, eatA (ETEC
      autotransporter A), encodes a potential serine protease motif (GDSGSP) in the
      secreted amino-terminal domain, and the predicted peptide shows more than 80%
      homology with SepA, a virulence protein secreted by Shigella flexneri. DNA
      hybridization and PCR demonstrated that eatA resides on the 92-kDa pCS1 virulence
      plasmid of H10407 and that it is present in multiple clinical ETEC strains.
      Immunoblots with antisera directed against a recombinant EatA passenger protein
      fragment identified a 110-kDa protein in supernatants purified from H10407 but
      not from the TnphoA.977 mutant or H10407-P, which lacks pCS1. EatA possesses
      serine protease activity that is abolished by mutations within a serine protease
      catalytic triad formed by residues H(134), D(162), and S(267). Finally,
      interruption of the eatA gene retarded fluid accumulation in the rabbit ileal
      loop model, suggesting that this autotransporter contributes to the virulence of
      ETEC.

PMID- 14977989
TI  - Inhibitory effect of antiserum to surface antigen P50 of Babesia gibsoni on
      growth of parasites in severe combined immunodeficiency mice given canine red
      blood cells.
AB  - The inhibitory effect of an antiserum to surface protein P50 of Babesia gibsoni
      on the growth of the parasite was determined with severe combined
      immunodeficiency mice given canine red blood cells. The antiserum to the
      recombinant P50 protein significantly inhibited the parasite growth, indicating
      that P50 might be a useful vaccine candidate.

PMID- 14977990
TI  - Identification of srv, a PrfA-like regulator of group A streptococcus that
      influences virulence.
AB  - We have identified a Crp/Fnr-like transcriptional regulator of Streptococcus
      pyogenes that when inactivated attenuates virulence. The gene, named srv for
      streptococcal regulator of virulence, encodes a 240-amino-acid protein with 53%
      amino acid similarity to PrfA, a transcriptional activator of virulence in
      Listeria monocytogenes.

PMID- 14977991
TI  - Rat neutrophils prevent the development of tuberculosis.
AB  - To understand the role of neutrophils in the development of rat tuberculosis in
      vivo, we utilized lipopolysaccharide (LPS)-induced neutrophilia in the lungs. LPS
      (50 micro g/ml) was administered intratracheally to male Fischer rats. Rats were
      then infected with Mycobacterium tuberculosis by an airborne route. Intratracheal
      injection of LPS significantly blocked the development of pulmonary granulomas
      and significantly reduced pulmonary CFU (P < 0.01). LPS treatment with
      amphotericin B (an LPS inhibitor) or neutralizing anti-rat neutrophil antibody
      reversed the development of pulmonary lesions. LPS-induced transient neutrophilia
      prevented early mycobacterial infection. The timing of LPS administration was
      important. When given intratracheally at least 10 days after aerial infection,
      LPS did not prevent development of tuberculosis. Neutrophils obtained by
      bronchoalveolar lavage killed M. tuberculosis cells. These results indicate
      clearly that neutrophils participate actively in defense against early-phase
      tuberculosis.

PMID- 14977992
TI  - Mycobacterial purified protein derivatives stimulate innate immunity: Malawians
      show enhanced tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL
      10 responses compared to those of adolescents in the United Kingdom.
AB  - To investigate the role of innate immunity in variable efficacy of Mycobacterium
      bovis BCG vaccination in Malawi and the United Kingdom, we examined 24-h tumor
      necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-10 responses to
      mycobacterial purified protein derivatives (PPDs). The rank order in stimulatory
      potency for different PPDs was the same for all three cytokines. Before
      vaccination Malawians made higher pro- and anti-inflammatory responses than did
      United Kingdom subjects. Fewer than 5% of United Kingdom subjects made IL-10 in
      response to any PPD, compared to 19 to 57% responders among Malawians. Priming
      for regulatory IL-10 may contribute to the smaller increase in gamma interferon
      responses in Malawians compared to United Kingdom subjects following BCG
      vaccination.

PMID- 14977993
TI  - Characterization of cytolethal distending toxin genes and expression in shiga
      toxin-producing Escherichia coli strains of non-O157 serogroups.
AB  - We identified cytolethal distending toxin and its gene (cdt) in 17 of 340 non
      O157 Shiga toxin-producing Escherichia coli (STEC) strains (serotypes O73:H18,
      O91:H21, O113:H21, and O153:H18), all of which were eae negative. cdt is either
      chromosomal and homologous to cdt-V (serotypes O73:H18, O91:H21, and O113:H21) or
      plasmidborne and identical to cdt-III (serotype O153:H18). Among eae-negative
      STEC, cdt was associated with disease (P = 0.003).

PMID- 14977994
TI  - Inclusion of CpG adjuvant with plasmid DNA coding for NcGRA7 improves protection
      against congenital neosporosis.
AB  - The present study showed that incorporation of CpG adjuvant into plasmid DNA
      coding for NcGRA7 antigen resulted in a twofold increase in the level of
      protection against congenital transfer of Neospora caninum. The level of
      protection was considerably higher than that observed in pups born from dams
      immunized with nonrecombinant plasmid.

PMID- 14977995
TI  - Highly purified vitamin B2 presents a promising therapeutic strategy for sepsis
      and septic shock.
AB  - Highly purified vitamin B2 (riboflavin 5'-sodium phosphate; purity > 97%)
      treatment by intravenous infusion at doses above those used clinically to treat
      vitamin B2 deficiency showed therapeutic effects in mice not only in cases of
      endotoxin- and exotoxin-induced shock but also in cases of gram-negative and gram
      positive bacterial infection even after the toxemia had already begun.

PMID- 14977996
TI  - Detection of antibodies to toxin-coregulated pili in sera from cholera patients.
AB  - Monoclonal antibodies (MAbs) were prepared against toxin-coregulated pili (TCP)
      isolated from Vibrio cholerae O1 El Tor. Despite their limited bactericidal
      potential, two MAbs were able to mediate biotype-specific protection against
      experimental cholera in infant mice. These MAbs were used in immunoblotting
      studies to assess seroconversion to El Tor TCP following cholera. Clear anti
      pilus responses were observed in five of nine patients.

PMID- 14977997
TI  - Heterozygous toll-like receptor 2 polymorphism does not affect lipoteichoic acid
      induced chemokine and inflammatory responses.
AB  - While transfection of tlr2 conveyed responsiveness to lipoteichoic acid (LTA),
      the Arg753Gln polymorphic gene could not. LTA induced a stronger chemokine and
      anti-inflammatory response than lipopolysaccharides did. Blood from heterozygous
      polymorphic and wild-type donors reacted uniformly to LTA and Staphylococcus
      aureus. Thus, one functional allele for Toll-like receptor 2 suffices for full
      cytokine response.

PMID- 14977998
TI  - Impacts of sarA and agr in Staphylococcus aureus strain Newman on fibronectin
      binding protein A gene expression and fibronectin adherence capacity in vitro and
      in experimental infective endocarditis.
AB  - We investigated the impacts of sarA and agr on fnbA expression and fibronectin
      binding capacity in Staphylococcus aureus in vitro and in experimental
      endocarditis. Although sarA up-regulated and agr down-regulated both fnbA
      expression and fibronectin binding in vitro and in vivo, fnbA expression was
      positively regulated in the absence of both global regulators. Thus, additional
      regulatory loci contribute to fnbA regulation and fibronectin-binding capacities
      in S. aureus.

PMID- 14977999
TI  - Shiga toxin 1 targets bovine leukemia virus-expressing cells.
AB  - Direct evidence that Escherichia coli Shiga toxin (Stx) acts against bovine
      leukemia virus (BLV)-expressing cells was obtained. The active A subunit of Stx
      type 1 (StxA1) targeted a selected population of permeable cells expressing BLV
      and inhibited BLV replication in a culture of bovine peripheral blood mononuclear
      cells. Cells were cultured with and without StxA1, and at various times cells
      expressing BLV were identified by being stained with MW1 monoclonal antibody
      specific for the BLV protein gp51. Before culture, permeable cells were tagged by
      uptake of one of the following: acetoxymethyl of 2',7'-bis-(2-carboxyethyl)-5
      (and 6)-carboxyfluorescein (BCECF), BCECF conjugated to 70-kDa dextran, or 70-kDa
      dextran conjugated to fluorescein. The tagged cells costaining with anti-gp51
      were selectively eliminated in StxA1-treated cultures. Electron microscopy
      analysis of purified B lymphocytes showed sharply reduced numbers of BLV
      particles in StxA1-treated cultures.

PMID- 14978000
TI  - Phenotypes of Plasmodium falciparum from the peripheral blood of pregnant women.

PMID- 14978001
TI  - Parasympathetic control of the heart. II. A novel interganglionic intrinsic
      cardiac circuit mediates neural control of heart rate.
AB  - Intracardiac pathways mediating the parasympathetic control of various cardiac
      functions are incompletely understood. Several intracardiac ganglia have been
      demonstrated to potently influence cardiac rate [the sinoatrial (SA) ganglion],
      atrioventricular (AV) conduction (the AV ganglion), or left ventricular
      contractility (the cranioventricular ganglion). However, there are numerous
      ganglia found throughout the heart whose functions are poorly characterized. One
      such ganglion, the posterior atrial (PA) ganglion, is found in a fat pad on the
      rostral dorsal surface of the right atrium. We have investigated the potential
      impact of this ganglion on cardiac rate and AV conduction. We report that
      microinjections of a ganglionic blocker into the PA ganglion significantly
      attenuates the negative chronotropic effects of vagal stimulation without
      significantly influencing negative dromotropic effects. Because prior evidence
      indicates that the PA ganglion does not project to the SA node, we
      neuroanatomically tested the hypothesis that the PA ganglion mediates its effect
      on cardiac rate through an interganglionic projection to the SA ganglion.
      Subsequent to microinjections of the retrograde tracer fast blue into the SA
      ganglion, >70% of the retrogradely labeled neurons found within five intracardiac
      ganglia throughout the heart were observed in the PA ganglion. The neuroanatomic
      data further indicate that intraganglionic neuronal circuits are found within the
      SA ganglion. The present data support the hypothesis that two interacting cardiac
      centers, i.e., the SA and PA ganglia, mediate the peripheral parasympathetic
      control of cardiac rate. These data further support the emerging concept of an
      intrinsic cardiac nervous system.

PMID- 14978002
TI  - Parasympathetic control of the heart. I. An interventriculo-septal ganglion is
      the major source of the vagal intracardiac innervation of the ventricles.
AB  - The locations, projections, and functions of the intracardiac ganglia are
      incompletely understood. Immunocytochemical labeling with the general neuronal
      marker protein gene product 9.5 (PGP 9.5) was used to determine the distribution
      of intracardiac neurons throughout the cat atria and ventricles. Fluorescence
      microscopy was used to determine the number of neurons within these ganglia.
      There are eight regions of the cat heart that contain intracardiac ganglia. The
      numbers of neurons found within these intracardiac ganglia vary dramatically. The
      total number of neurons found in the heart (6,274 +/- 1,061) is almost evenly
      divided between the atria and the ventricles. The largest ganglion is found in
      the interventricular septum (IVS). Retrogradely labeled fluorescent tracer
      studies indicated that the vagal intracardiac innervation of the anterior surface
      of the right ventricle originates predominantly in the IVS ganglion. A
      cranioventricular (CV) ganglion was retrogradely labeled from the anterior
      surface of the left ventricle but not from the anterior surface of the right
      ventricle. These new neuroanatomic data support the prior physiological
      hypothesis that the CV ganglion in the cat exerts a negative inotropic effect on
      the left ventricle. A total of three separate intracardiac ganglia innervate the
      left ventricle, i.e., the CV, IVS, and a second left ventricular (LV2) ganglion.
      However, the IVS ganglion provides the major source of innervation to both the
      left and right ventricles. This dual innervation pattern may help to coordinate
      or segregate vagal effects on left and right ventricular performance.

PMID- 14978003
TI  - Parasympathetic control of the heart. III. Neuropeptide Y-immunoreactive nerve
      terminals synapse on three populations of negative chronotropic vagal
      preganglionic neurons.
AB  - The vagal postganglionic control of cardiac rate is mediated by two intracardiac
      ganglia, i.e., the sinoatrial (SA) and posterior atrial (PA) ganglia. Nothing is
      known about the vagal preganglionic neurons (VPNs) that innervate the PA ganglion
      or about the neurochemical anatomy of central afferents that innervate these
      VPNs. These issues were examined using light microscopic retrograde labeling
      methods and dual-labeling electron microscopic histochemical and
      immunocytochemical methods. VPNs projecting to the PA ganglion are found in a
      narrow column exclusively in the ventrolateral nucleus ambiguus (NA-VL). These
      neurons are relatively large (37.6 +/- 2.7 microm by 21.3 +/- 3.4 microm) with
      abundant cytoplasm and intracellular organelles, rare somatic and dendritic
      spines, round uninvaginated nuclei, and myelinated axons. Previous physiological
      data indicated that microinjections of neuropeptide Y (NPY) into the NA-VL cause
      negative chronotropic effects. The present morphological data demonstrate that
      NPY-immunoreactive nerve terminals formed 18 +/- 4% of the axodendritic or
      axosomatic synapses and close appositions on VPNs projecting to the PA ganglion.
      Three approximately equal populations of VPNs in the NA-VL were retrogradely
      labeled from the SA and PA ganglia. One population each projects to the SA
      ganglion, the PA ganglion, or to both the SA and PA ganglia. Therefore, there are
      both shared and independent pathways involved in the vagal preganglionic controls
      of cardiac rate. These data are consistent with the hypothesis that the central
      and peripheral parasympathetic controls of cardiac rate are coordinated by
      multiple potentially redundant and/or interacting pathways and mechanisms.

PMID- 14978004
TI  - Muscle sympathetic nerve activity during lower body negative pressure is
      accentuated in heat-stressed humans.
AB  - The purpose of this project was to test the hypothesis that increases in muscle
      sympathetic nerve activity (MSNA) during an orthostatic challenge is attenuated
      in heat-stressed individuals. To accomplish this objective, MSNA was measured
      during graded lower body negative pressure (LBNP) in nine subjects under
      normothermic and heat-stressed conditions. Progressive LBNP was applied at -3, 
      6, -9, -12, -15, -18, -21, and -40 mmHg for 2 min per stage. Whole body heating
      caused significant increases in sublingual temperature, skin blood flow, sweat
      rate, heart rate, and MSNA (all P < 0.05) but not in mean arterial blood pressure
      (P > 0.05). Progressive LBNP induced significant increases in MSNA in both
      thermal conditions. However, during the heat stress trial, increases in MSNA at
      LBNP levels higher than -9 mmHg were greater compared with during the same LBNP
      levels in normothermia (all P < 0.05). These data suggest that the increase in
      MSNA to orthostatic stress is not attenuated but rather accentuated in heat
      stressed humans.

PMID- 14978005
TI  - Exertional heat injury and gene expression changes: a DNA microarray analysis
      study.
AB  - This study examined gene expression changes associated with exertional heat
      injury (EHI) in vivo and compared these changes to in vitro heat shock responses
      previously reported by our laboratory. Peripheral blood mononuclear cell (PBMC)
      RNA was obtained from four male Marine recruits (ages 17-19 yr) who presented
      with symptoms consistent with EHI, core temperatures ranging from 39.3 to 42.5
      degrees C, and elevations in serum enzymes such as creatine kinase. Controls were
      age- and gender-matched Marines from whom samples were obtained before and
      several days after an intense field-training exercise in the heat ("The
      Crucible"). Expression analysis was performed on Affymetrix arrays (containing
      approximately 12,600 sequences) from pooled samples obtained at three times for
      EHI group (at presentation, 2-3 h after cooling, and 1-2 days later) and compared
      with control values (average signals from two chips representing pre- and post
      Crucible samples). After post hoc filtering, the analysis identified 361
      transcripts that had twofold or greater increases in expression at one or more of
      the time points assayed and 331 transcripts that had twofold or greater decreases
      in expression. The affected transcripts included sequences previously shown to be
      heat-shock responsive in PBMCs in vitro (including both heat shock proteins and
      non-heat shock proteins), a number of sequences whose changes in expression had
      not previously been noted as a result of in vitro heat shock in PBMCs (including
      several interferon-induced sequences), and several nonspecific stress response
      genes (including ubiquitin C and dual-specificity phosphatase-1). We conclude
      that EHI produces a broad stress response that is detectable in PBMCs and that
      heat stress per se can only account for some of the observed changes in
      transcript expression. The molecular evidence from these patients is thus
      consistent with the hypothesis that EHI can result from cumulative effects of
      multiple adverse interacting stimuli.

PMID- 14978006
TI  - Use of phosphocreatine kinetics to determine the influence of creatine on muscle
      mitochondrial respiration: an in vivo 31P-MRS study of oral creatine ingestion.
AB  - Recent human isolated muscle fiber studies suggest that phosphocreatine (PCr) and
      creatine (Cr) concentrations play a role in the regulation of mitochondrial
      respiration rate. To determine whether similar regulatory mechanisms are present
      in vivo, this study examined the relationship between skeletal muscle
      mitochondrial respiration rate and end-exercise PCr, Cr, PCr-to-Cr ratio
      (PCr/Cr), ADP, and pH by using (31)P-magnetic resonance spectroscopy in 16 men
      and women (36.9 +/- 4.6 yr). The initial PCr resynthesis rate and time constant
      (T(c)) were used as indicators of mitochondrial respiration after brief (10-12 s)
      and exhaustive (1-4 min) dynamic knee extension exercise performed in placebo and
      creatine-supplemented conditions. The results show that the initial PCr
      resynthesis rate has a strong relationship with end-exercise PCr, Cr, and PCr/Cr
      (r > 0.80, P < 0.001), a moderate relationship with end-exercise ADP (r = 0.77, P
      < 0.001), and no relationship with end-exercise pH (r = -0.14, P = 0.34). The PCr
      T(c) was not as strongly related to PCr, Cr, PCr/Cr, and ADP (r < 0.77, P < 0.001
      0.18) and was significantly influenced by end-exercise pH (r = -0.43, P < 0.01).
      These findings suggest that end-exercise PCr and Cr should be taken into
      consideration when PCr recovery kinetics is used as an indicator of mitochondrial
      respiration and that the initial PCr resynthesis rate is a more reliable
      indicator of mitochondrial respiration compared with the PCr T(c).

PMID- 14978007
TI  - Interactions in hypoxic and hypercapnic breathing are genetically linked to mouse
      chromosomes 1 and 5.
AB  - The genetic basis for differences in the regulation of breathing is certainly
      multigenic. The present paper builds on a well-established genetic model of
      differences in breathing using inbred mouse strains. We tested the interactive
      effects of hypoxia and hypercapnia in two strains of mice known for variation in
      hypercapnic ventilatory sensitivity (HCVS); i.e., high gain in C57BL/6J (B6) and
      low gain in C3H/HeJ (C3) mice. Strain differences in the magnitude and pattern of
      breathing were measured during normoxia [inspired O(2) fraction (Fi(O(2))) =
      0.21] and hypoxia (Fi(O(2)) = 0.10) with mild or severe hypercapnia (inspired
      CO(2) fraction = 0.03 or 0.08) using whole body plethysmography. At each level of
      Fi(O(2)), the change in minute ventilation (Ve) from 3 to 8% CO(2) was computed,
      and the strain differences between B6 and C3 mice in HCVS were maintained.
      Inheritance patterns showed potentiation effects of hypoxia on HCVS (i.e., CO(2)
      potentiation) unique to the B6C3F1/J offspring of B6 and C3 progenitors; i.e.,
      the change in Ve from 3 to 8% CO(2) was significantly greater (P < 0.01) with
      hypoxia relative to normoxia in F1 mice. Linkage analysis using intercross
      progeny (F2; n = 52) of B6 and C3 progenitors revealed two significant
      quantitative trait loci associated with variable HCVS phenotypes. After
      normalization for body weight, variation in Ve responses during 8% CO(2) in
      hypoxia was linked to mouse chromosome 1 (logarithm of the odds ratio = 4.4) in
      an interval between 68 and 89 cM (i.e., between D1Mit14 and D1Mit291). The second
      quantitative trait loci linked differences in CO(2) potentiation to mouse
      chromosome 5 (logarithm of the odds ratio = 3.7) in a region between 7 and 29 cM
      (i.e., centered at D5Mit66). In conclusion, these results support the hypothesis
      that a minimum of two significant genes modulate the interactive effects of
      hypoxia and hypercapnia in this genetic model.

PMID- 14978008
TI  - Alpha-adrenoceptor-mediated coronary vasoconstriction is augmented during
      exercise in experimental diabetes mellitus.
AB  - This study tested whether alpha-adrenoceptor-mediated coronary vasoconstriction
      is augmented during exercise in diabetes mellitus. Experiments were conducted in
      dogs instrumented with catheters in the aorta and coronary sinus and with a flow
      transducer around the circumflex coronary artery. Diabetes was induced with
      alloxan monohydrate (n = 8, 40 mg/kg i.v.). Arterial plasma glucose concentration
      increased from 4.7 +/- 0.2 mM in nondiabetic, control dogs (n = 8) to 21.4 +/-
      1.9 mM 1 wk after alloxan injection. Coronary blood flow, myocardial oxygen
      consumption (MVo(2)), aortic pressure, and heart rate were measured at rest and
      during graded treadmill exercise before and after infusion of the alpha
      adrenoceptor antagonist phentolamine (1 mg/kg iv). In untreated diabetic dogs,
      exercise increased MVo(2) 2.7-fold, coronary blood flow 2.2-fold, and heart rate
      2.3-fold. Coronary venous Po(2) fell as MVo(2) increased during exercise. After
      alpha-adrenoceptor blockade, exercise increased MVo(2) 3.1-fold, coronary blood
      flow 2.7-fold, and heart rate 2.1-fold. Relative to untreated diabetic dogs,
      alpha-adrenoceptor blockade significantly decreased the slope of the relationship
      between coronary venous Po(2) and MVo(2). The difference between the untreated
      and phentolamine-treated slopes was greater in the diabetic dogs than in the
      nondiabetic dogs. In addition, the decrease in coronary blood flow to
      intracoronary norepinephrine infusion was significantly augmented in
      anesthetized, open-chest, beta-adrenoceptor-blocked diabetic dogs compared with
      the nondiabetic dogs. These findings demonstrate that alpha-adrenoceptor-mediated
      coronary vasoconstriction is augmented in alloxan-induced diabetic dogs during
      physiological increases in MVo(2).

PMID- 14978009
TI  - Hypergravity-induced immunomodulation in a rodent model: hematological and
      lymphocyte function analyses.
AB  - The major purpose of this study was to quantify hypergravity-induced changes in
      erythrocyte and thrombocyte characteristics, spontaneous and mitogen-induced
      lymphoblastogenesis, and capacity of splenocytes to secrete immunoregulatory
      cytokines. C57BL/6 mice were subjected to chronic 1, 2, and 3 G; subsets were
      euthanized after 1, 4, 7, 10, and 21 days of centrifugation. Erythrocyte counts,
      hematocrit, and hemoglobin were significantly reduced by day 21 in both
      centrifuged groups. Hemoglobin concentration and volume per red blood cell were
      generally low, but an early, transient spike above normal was noted in
      thrombocyte counts in the 3-G group. Fluctuations above and below normal in blood
      and spleen cell spontaneous blastogenesis were dependent on the length of
      centrifugation time and not on the level of gravity. Depression in splenocyte
      responses to phytohemagglutinin and lipopolysaccharide due to gravity were noted
      when the data were expressed as stimulation indexes. Cytokine production by
      spleen cells was primarily affected during the first week of centrifugation: IL
      2, IL-4, and tumor necrosis factor-alpha increased, whereas interferon-gamma
      decreased. These findings, although not identical to those reported for
      spaceflight, indicate that altered gravity can influence both hematological and
      functional variables that may translate into serious health consequences during
      extended missions.

PMID- 14978010
TI  - Adding fat calories to meals after exercise does not alter glucose tolerance.
AB  - A single session of exercise increases insulin sensitivity for hours and even
      days, and dietary carbohydrate ingested after exercise alters the magnitude and
      duration of this effect. Although increasing systemic fatty acid availability is
      associated with insulin resistance, it is uncertain whether increasing dietary
      fat availability after exercise alters the exercise-induced increase in insulin
      sensitivity. The purpose of this study was to determine whether adding fat
      calories to meals after exercise alters glucose tolerance the next day. Seven
      healthy men cycled 90 min at 66 +/- 2% peak oxygen uptake followed by a maximum
      of five high-intensity intervals. During the hours after exercise, subjects
      ingested three meals containing either low-fat (5% energy from fat) or high-fat
      (45% energy from fat) foods (Low-Fat and High-Fat groups, respectively). Each
      diet contained the same amount of carbohydrate and protein. An oral glucose
      tolerance test was performed the next morning. Muscle glycogen and intramuscular
      triglyceride (IMTG) concentrations were measured in muscle biopsy samples
      obtained immediately before exercise and the next morning. The day after
      exercise, muscle glycogen concentration was identical in High-Fat and Low-Fat
      (393 +/- 70 and 379 +/- 38 mmol/kg dry wt). At the same time, IMTG concentration
      was approximately 20% greater during High-Fat compared with Low-Fat (42.5 +/- 3.4
      and 36.3 +/- 3.3 mmol/kg dry wt; P < 0.05). Despite the addition of approximately
      165 g of fat to meals after exercise ( approximately 1,500 kcal) and a resultant
      elevation in IMTG concentration, glucose tolerance was identical in High-Fat and
      Low-Fat (composite index: 8.7 +/- 1.0 and 8.4 +/- 1.0). In summary, as long as
      meals ingested in the hours after exercise contain the same carbohydrate content,
      the addition of approximately 1500 kcal from fat to these meals did not alter
      muscle glycogen resynthesis or glucose tolerance the next day.

PMID- 14978011
TI  - Altered calcium sensitivity contributes to enhanced contractility of collateral
      dependent coronary arteries.
AB  - Coronary arteries distal to chronic occlusion exhibit enhanced vasoconstriction
      and impaired relaxation compared with nonoccluded arteries. In this study, we
      tested the hypotheses that an increase in peak Ca(2+) channel current density
      and/or increased Ca(2+) sensitivity contributes to altered contractility in
      collateral-dependent coronary arteries. Ameroid occluders were surgically placed
      around the proximal left circumflex coronary artery (LCX) of female miniature
      swine. Segments of epicardial arteries ( approximately 1 mm luminal diameter)
      were isolated from the LCX and nonoccluded left anterior descending (LAD)
      arteries 24 wk after Ameroid placement. Contractile responses to depolarization
      (10-100 mM KCl) were significantly enhanced in LCX compared with size-matched LAD
      arterial rings [concentration of KCl causing 50% of the maximal contractile
      response (EC(50)); LAD = 41.7 +/- 2.3, LCX = 34.3 +/- 2.7 mM]. However, peak
      Ca(2+) channel current was not altered in isolated smooth muscle cells from LCX
      compared with LAD (-5.29 +/- 0.42 vs. -5.68 +/- 0.55 pA/pF, respectively).
      Furthermore, whereas half-maximal activation of Ca(2+) channel current occurred
      at nearly the same membrane potential in LAD and LCX, half-maximal inactivation
      was shifted to a more positive membrane potential in LCX cells. Simultaneous
      measures of contractile tension and intracellular free Ca(2+) (fura 2) levels in
      arterial rings revealed that significantly more tension was produced per unit
      change in fura 2 ratio in LCX compared with LAD in response to KCl but not during
      receptor-agonist stimulation with endothelin-1. Taken together, our data indicate
      that coronary arteries distal to chronic occlusion display increased Ca(2+)
      sensitivity in response to high KCl-induced depolarization, independent of
      changes in whole cell peak Ca(2+) channel current. Unaltered Ca(2+) sensitivity
      in endothelin-stimulated arteries suggests more than one mechanism regulating
      Ca(2+) sensitization in coronary smooth muscle.

PMID- 14978012
TI  - Augmentation of NK cell-mediated cytotoxicity to tumor cells by inhibitory NK
      cell receptor blockers.
AB  - NK cells monitor expression of MHC class I by inhibitory receptors and
      preferentially kill cells that lose or down-regulate MHC class I expression. One
      possible mechanism by which tumor cells evade NK cell killing is continued
      expression of appropriate MHC class I ligands to engage inhibitory receptors on
      NK cells. We show here that small-mol.-wt blockers against the mouse inhibitory
      NK cell receptor Ly49A enhance NK cell killing of such tumor cells. We identified
      Ly49A-binding peptides by selecting phages with the capacity to bind recombinant
      Ly49A expressed in Escherichia coli from a phage display random peptide library.
      The Ly49A-binding peptides could also bind Ly49A expressed on mammalian cells.
      Importantly, the Ly49A-binding peptides blocked Ly49A recognition of its MHC
      class I ligands H-2Dd and H-2Dk. Moreover, blockade of Ly49A by the peptides
      enhanced cytotoxicity of Ly49A+ NK cells towards H-2Dd-expressing tumor cells.
      These results clearly indicate effectiveness of small-mol.-wt blockers of
      inhibitory NK cell receptors in enhancing NK cell-mediated killing of tumor cells
      that are otherwise resistant because of MHC class I expression.

PMID- 14978013
TI  - Induction of activation-induced cytidine deaminase gene expression by IL-4 and
      CD40 ligation is dependent on STAT6 and NFkappaB.
AB  - Activation-induced cytidine deaminase (AID) is an inducible gene that plays an
      important role in class switch recombination, somatic hypermutation and gene
      conversion in B cells. We examined the regulation of AID gene expression in human
      and mouse B cells by IL-4 and CD40 ligation. IL-4 by itself and, to a much lesser
      extent, CD40 ligation induced AID mRNA expression in primary B cells. The two
      stimuli strongly synergized in inducing AID mRNA and protein expression. IL-4
      induced STAT6 binding to a site in the 5' upstream region of the AID gene, while
      CD40 ligation induced NFkappaB binding to two sites in that region. B cells from
      STAT6-/- mice failed to up-regulate AID in response to IL-4, while B cells from
      p50-/- mice were impaired in their ability to up-regulate AID in response to CD40
      ligation and IL-4. These results suggest that signals delivered via CD40 that
      activate NFkappaB synergize with signals delivered via the IL-4 receptor that
      activate STAT6 to induce optimal AID gene expression.

PMID- 14978014
TI  - T cell recognition of a highly conserved epitope in heat shock protein 60: self
      tolerance maintained by TCR distinguishing between asparagine and aspartic acid.
AB  - Cross-reactive T cell recognition of self-heat shock proteins (hsp) has been
      ascribed a regulatory role in inflammatory arthritis in both animal models and
      human disease. The previous work implies that a repertoire for epitopes in self
      hsp60 should exist in normal subjects. Accordingly, we sought to generate self
      hsp60-reactive T cell clones from a healthy individual using a highly purified
      preparation of recombinant human (Hu) hsp60. Epitope mapping using synthetic
      peptides and truncated constructs indicated that the T cell clones obtained
      actually recognized hsp60 derived from Escherichia coli. Using a series of
      alanine-substituted peptides and additional appropriate synthetic peptides, it
      was demonstrated that the clones maintain self-tolerance because of their
      sensitivity to an asparagine to aspartic acid sequence difference between E. coli
      and HuHsp60 in the epitope-containing peptide. In addition, despite substantial
      conservation of sequence, the homologous peptide from HuHsp60 did not compete
      with the E. coli-derived peptide for recognition or antagonize responses by
      acting as an altered peptide ligand. The results suggest that, even when the
      immune system targets a highly conserved epitope in bacterial hsp60, self
      tolerance is maintained. Furthermore, the finding that T cell clones specific for
      minor contaminant proteins in HuHsp60 preparations can readily be isolated raises
      the possibility that the HuHsp60 facilitates presentation of antigenic proteins
      to the immune system.

PMID- 14978015
TI  - Protective T cell response against intracellular pathogens in the absence of Toll
      like receptor signaling via myeloid differentiation factor 88.
AB  - Toll-like receptors (TLR) have been indicated as germline-encoded receptors for
      sensing a variety of pathogens. Although the role of TLR in innate immunity is
      beyond question, their function in acquired immunity, in particular in T cell
      immunity, is less clear. Here, we used experimental Listeria monocytogenes
      infection of mice to analyze requirements for TLR2, TLR4 and the central TLR
      adaptor protein myeloid differentiation factor 88 (MyD88) in the generation of
      specific T cell responses. We demonstrate that following L. monocytogenes
      infection, mice deficient in TLR2, TLR4 and MyD88 can generate Listeria-specific
      CD8+ and CD4+ Th1 responses. These T cell responses are sufficient to control
      secondary infection with a high dose of L. monocytogenes even in the absence of
      TLR signaling via MyD88. Thus, TLR2-, TLR4- and MyD88-dependent signals are not
      essential for the generation of CD4+ Th1 and CD8+ T cells, and T cells can
      protect mice against infection in the absence of these signals.

PMID- 14978016
TI  - Development of TCRB CDR3 length repertoire of human T lymphocytes.
AB  - The third complementarity-determining region (CDR3) of TCR interacts directly
      with antigenic peptides bound to grooves of MHC molecules. Thus, it is the most
      critical TCR structure in launching acquired immunity and in determining fates of
      developing thymocytes. Since length is one of the components defining the CDR3
      heterogeneity, the CDR3 length repertoires have been studied in various T cell
      subsets from humans in physiological and pathological conditions. However, how
      the CDR3 length repertoire develops has been addressed only by a few reports,
      including one showing that CDR3 of CD4 thymocytes becomes shorter during thymic
      development. Here, we explored multiple regulations on the development of the
      TCRB CDR3 length repertoires in the thymus and the peripheral blood. CDR3 length
      spectratyping was employed to examine thymocyte and peripheral T cell populations
      for their CDR3 length repertoires. We have found that repertoire distribution
      patterns depend on use of the BV gene. The BV-dependent patterns were shaped
      during thymic selections and maintained in the peripheral blood. Differences in
      the mean CDR3 length among different BV subsets were seen throughout lymphocyte
      development. We also observed that CDR3 was shortened in both CD4 and CD8
      thymocytes. Of note, the degrees of the shortening depended on the CD4/CD8
      lineage and on use of the BV gene. When expansions of peripheral T cell clones
      are negligible, no obvious difference was seen between mature thymocytes and
      peripheral lymphocytes. Thus, the TCRB CDR3 length repertoires are finely tuned
      in the thymus before the lymphocytes emigrate into the peripheral blood.

PMID- 14978017
TI  - Early events associated to the oral co-administration of type II collagen and
      chitosan: induction of anti-inflammatory cytokines.
AB  - Oral administration of an antigen can result in local and systemic priming or
      tolerance and the basis of this dichotomy is poorly understood. The intestinal
      microenvironment, and factors such as nature of the antigen, dose, genetic
      background, uptake and concentration of the antigen that gain access to the
      internal milieu via the mucosa influence these active immunologic processes.
      Chitosan is a biocompatible natural polysaccharide able to promote the
      transmucosal absorption of peptides and proteins. The aim of our work was to
      study the effect of the co-administration of type II collagen (CII) and chitosan
      during the initial contact of the antigen with the immune system. Sixteen hours
      after feeding we evaluated several molecular events in mucosal and in systemic
      lymphoid tissues. We determined in Peyer's patches (PP) and spleen cells the
      number and activation of T cells, the arrival of the antigens, and the cytokine
      profile. In PP we found a reduction in the cell number without changes in CD3(+)
      cells. In spleen, instead, we observed an increase in CD3(+) cells as well as the
      internalization of the CD3 complex. CII:chitosan-fed animals exhibited a reduced
      secretion of IL-2 with an increase of IL-10 in PP and spleen respectively. In
      addition, in PP, CII:chitosan-fed rats showed increased levels of mRNA for
      transforming growth factor-beta, IL-4 and IL-10. Together, our data suggest that
      the co-administration with chitosan modifies the uptake and/or the distribution
      of the relevant antigen, and promotes an anti-inflammatory environment early
      after feeding.

PMID- 14978018
TI  - Survival of activated human T lymphocytes is promoted by retinoic acid via
      induction of IL-2.
AB  - At the end of an immune response, most activated T cells spontaneously undergo
      programmed cell death (apoptosis). In the present study we show that all-trans
      retinoic acid (atRA), a major vitamin A metabolite, can inhibit the spontaneous
      apoptosis of activated human T lymphocytes in vitro. Isolated peripheral blood T
      lymphocytes were activated by 12-O-tetradecanoyl phorbol 13-acetate and cultured
      for up to 11 days without any further stimuli. With time, a gradual increase in
      cell death was observed. This spontaneous death of activated T cells was
      apoptotic, as demonstrated by cell shrinkage, DNA fragmentation and
      depolarization of the mitochondrial membrane. In the presence of physiological
      concentrations of atRA, the percentage of T cells exhibiting these apoptotic
      features was significantly reduced. After 5 days of stimulation, the percentage
      of TUNEL+ T cells decreased from 28 to 12% in the presence of atRA. The anti
      apoptotic effect of atRA was mimicked by the retinoic acid receptor (RAR)
      selective agonists 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2
      naphthalenyl)-1-propenyl]benzoic acid and AM-580, and totally abrogated by the
      RAR-selective antagonist Ro 41-5253. Cytokines of the IL-2 family have been shown
      to improve the survival of activated T cells. Strikingly, we found that the
      ability of atRA to inhibit apoptosis was significantly correlated with its
      ability to increase the production of IL-2. Furthermore, a blocking anti-IL-2
      receptor antibody completely abrogated the anti-apoptotic effect of atRA.
      Together, these results suggest that retinoic acid inhibits spontaneous apoptosis
      of activated T lymphocytes through a RAR-dependent increase in IL-2 production.

PMID- 14978019
TI  - The point mutation of tyrosine 759 of the IL-6 family cytokine receptor gp130
      synergizes with HTLV-1 pX in promoting rheumatoid arthritis-like arthritis.
AB  - Rheumatoid arthritis (RA) is a polygenic autoimmune disease. The autoimmunity
      develops from synergistic actions of genetic and environmental factors. We
      generated a double-mutant mouse by crossing two murine models of RA, a gp130
      mutant knock-in mouse (gp130F759/F759) and an HTLV-1 pX transgenic mouse (pX-Tg),
      in a C57BL/6 background, which is resistant to arthritis. The mice spontaneously
      developed severe arthritis with a much earlier onset than the gp130F759/F759 mice
      and with a much higher incidence than did the pX-Tg mice. The symptoms of
      gp130F759/F759 mice, including lymphoadenopathy, splenomegaly, hyper-gamma
      globulinemia, autoantibody production, increases in memory/activated T cells and
      granulocytes in the peripheral lymphoid organs, and a decrease in the class II
      MHC(bright) CD11c+ population, were augmented in the double mutants. Marked
      reductions in incidence, severity and immunological abnormalities were seen in
      the triple mutant, IL-6-/-/gp130F759/F759/pX-Tg, indicating that the arthritis in
      the double mutant is IL-6 dependent. gp130F759/F759/pX-Tg is a unique mouse model
      for RA.

PMID- 14978020
TI  - BAFF production by antigen-presenting cells provides T cell co-stimulation.
AB  - The B cell-activating factor from the tumor necrosis factor family (BAFF) is an
      important regulator of B cell immunity. Recently, we demonstrated that
      recombinant BAFF also provides a co-stimulatory signal to T cells. Here, we
      studied expression of BAFF in peripheral blood leukocytes and correlated this
      expression with BAFF T cell co-stimulatory function. BAFF is produced by antigen
      presenting cells (APC). Blood dendritic cells (DC) as well as DC differentiated
      in vitro from monocytes or CD34+ stem cells express BAFF mRNA. Exposure to
      bacterial products further up-regulates BAFF production in these cells. A low
      level of BAFF transcription, up-regulated upon TCR stimulation, was also detected
      in T cells. Functionally, blockade of endogenous BAFF produced by APC and, to a
      lesser extent, by T cells inhibits T cell activation. Altogether, this indicates
      that BAFF may regulate T cell immunity during APC-T cell interactions and as an
      autocrine factor once T cells have detached from the APC.

PMID- 14978021
TI  - Osteopontin affects the persistence of beta-glucan-induced hepatic granuloma
      formation and tissue injury through two distinct mechanisms.
AB  - Osteopontin (OPN) plays a pivotal role in various immune responses and
      inflammatory diseases. OPN is expressed in various granulomatous diseases;
      however, the cellular and molecular role of OPN in these diseases is not well
      known. We analyzed the role of OPN in a beta-glucan-induced hepatic granuloma
      model. First, we found that neither OPN deficiency nor overexpression of OPN
      affected the number and the size of hepatic granulomas at day 7, indicating that
      OPN is not involved in the formation of hepatic granulomas at the early stages.
      Importantly, OPN did not influence the liver tissue damage as defined by alanine
      aminotransferase and aspartate aminotransferase levels at early stages. Second,
      OPN deficiency resulted in the reduction of IL-12 and IFN-gamma production at
      early stages. Third, at late stages, OPN deficiency resulted in a decrease in the
      number and size of hepatic granulomas, and a reduction of liver tissue injury.
      This was due to the reduction of the cellular recruitment including macrophages,
      CD4 T cells and dendritic cells into the liver, and the reduction of tumor
      necrosis factor (TNF)-alpha production in the liver. In contrast, overexpression
      of OPN resulted in the persistence of granuloma formation. These data suggest
      that OPN affects the persistence of hepatic granuloma formation. Our results
      indicate that OPN up-regulates the production of IL-12 and IFN-gamma within the
      granulomas at early stages, and OPN has an additional role in the regulation of
      cellular recruitment and TNF-alpha production at late stages that determine the
      severity of liver tissue injury.

PMID- 14978022
TI  - Tolerance induction by molecular mimicry: prevention and suppression of
      experimental autoimmune encephalomyelitis with the milk protein butyrophilin.
AB  - Multiple sclerosis (MS) is a common inflammatory disease of the central nervous
      system. Although the etiology of MS remains unknown, studies in experimental
      autoimmune encephalomyelitis (EAE) have suggested that foreign molecules, which
      show molecular mimicry with myelin antigens, may play an important role as
      causative agents of the human disease. In this study, we investigate the
      molecular mimicry between the extracellular Ig-like domain of the cow's milk
      protein butyrophilin (BTN) and the extracellular domain of myelin oligodendrocyte
      glycoprotein (MOG), a candidate autoantigen in MS. Interestingly, we found that
      as a result of a non-pathogenic cross-reactivity that is localized to a
      subdominant region of MOG, treatment of C57BL/6 mice with BTN either before or
      after immunization with MOG was shown to prevent and also suppress the clinical
      manifestations of EAE. BTN treatment resulted in a significant reduction in both
      proliferation and production of Th1-related cytokines (IFN-gamma, IL-2, IL-12 and
      granulocyte macrophage colony stimulating factor) in response to MOG. This
      specific inhibition was consistently associated with an up-regulation in IL-10
      secretion. Furthermore, adoptive transfer of BTN-specific T cells prior to active
      immunization with MOG resulted in a transitory reduction of the clinical
      symptoms. Our results suggest that the clinical improvement associated with BTN
      treatment involved the combination of both anergy and regulatory cells secreting
      high levels of IL-10. In conclusion, we show that despite the traditional link
      between molecular mimicry and pathogenic immune response, environmental agents
      that share homology with autoantigens may also represent a source of cells with a
      protective phenotype.

PMID- 14978023
TI  - IL-4-mediated inhibition of IFN-gamma production by CD4+ T cells proceeds by
      several developmentally regulated mechanisms.
AB  - The mechanisms by which Th1 and Th2 cells inter-regulate in vivo are still poorly
      understood. In this study we examined the plasticity of Th1 cell differentiation
      and how Th2 cells may down-regulate these responses. We show here that IL-4
      affects Th1 cell responses by two developmentally regulated mechanisms. During
      the commitment phase of naive CD4+ T cells, IL-4 inhibits Th1 cell
      differentiation and induces a reversion of developing Th1 cells to the Th2
      lineage. In contrast, for effector Th1 cells IL-4 does not affect the
      developmental process, but only the transcription of the IFN-gamma gene. We
      further show that the difference in IL-4 responsiveness correlates with a loss,
      in effector Th1 cells, of IL-4-dependent up-regulation of GATA-3 expression
      despite normal activation of STAT6. Transient inhibition of IFN-gamma production
      by differentiated effector cells may explain why Th1 and Th2 responses can co
      exist in vivo although Th2 effector cells dominate functionally, as observed in
      some infectious or autoimmune mice models.

PMID- 14978024
TI  - Toll-like receptor 4 plays a protective role in pulmonary tuberculosis in mice.
AB  - Toll-like receptors (TLR) play an essential role in the innate recognition of
      microorganisms by the host. To determine the role of TLR4 in host defense against
      lung tuberculosis, TLR4 mutant (C3H/HeJ) and wild-type (C3H/HeN) mice were
      intranasally infected with live Mycobacterium tuberculosis. TLR4 mutant mice were
      more susceptible to pulmonary tuberculosis, as indicated by a reduced survival
      and an enhanced mycobacterial outgrowth. Lung infiltrates were more profound in
      TLR4 mutant mice and contained more activated T cells. Splenocytes of infected
      TLR4 mutant mice demonstrated a reduced capacity to produce the protective type 1
      cytokine IFN-gamma upon antigen-specific stimulation, indicating that TLR4 may be
      involved in the generation of acquired T cell-mediated immunity. These data
      suggest that TLR4 plays a protective role in host defense against lung infection
      by M. tuberculosis.

PMID- 14978025
TI  - Natural human polyreactive IgM induce apoptosis of lymphoid cell lines and human
      peripheral blood mononuclear cells.
AB  - Natural polyreactive IgM autoantibodies, encoded by unmutated germline Ig V
      genes, represent a major fraction of the normal circulating IgM repertoire. We
      have previously shown that therapeutic preparation of pooled IgM exerts
      immunomodulatory effects as assessed by in vitro and in vivo studies. Here, we
      show that the IgM preparation induces cell death in lymphoblastoid cell lines and
      in human peripheral blood mononuclear cells. The IgM-induced cell death involved
      classical features of apoptosis such as nuclear fragmentation and activation of
      caspases. Treatment of leukemic cells with IgM resulted in the cleavage of poly
      (A)DP ribose polymerase, a substrate of caspase, and in a reduction in
      mitochondrial transmembrane potential during the early period of apoptosis
      induction. Natural IgM-induced apoptosis was inhibited by soluble Fas molecules
      and affinity-purified Fas antibodies from pooled IgM preparation induced
      apoptosis in lymphoblastoid cells, suggesting the involvement of the Fas
      receptor. Our results suggest a role for normal IgM in controlling cell death and
      proliferation, and imply a possible therapeutic role for IgM in autoimmune and
      lymphoproliferative disorders.

PMID- 14978026
TI  - Role of the helical protrusion in the conformational change and molecular
      chaperone activity of the archaeal group II chaperonin.
AB  - To elucidate the exact role of the helical protrusion of a group II chaperonin in
      its molecular chaperone function, three deletion mutants of the chaperonin from a
      hyperthermophilic archaeum (Thermococcus sp. strain KS-1) lacking one-third, two
      thirds, and the whole of the helical protrusion were constructed. The helical
      protrusion is thought to be substituted for the co-chaperonin GroES of a group I
      chaperonin and to be important for binding to unfolded proteins. Protease
      sensitivity assays and small angle x-ray scattering experiments were performed to
      demonstrate the conformation change of the wild type protein and the deletion
      mutants by adenine nucleotides. Whereas the binding of ATP to the wild type
      protein induced a structural transition corresponding to the closure of the built
      in lid, it did not cause significant structural changes in deletion mutants.
      Although the mutants effectively protected proteins from thermal aggregation, ATP
      dependent protein folding ability was remarkably diminished. We conclude that the
      helical protrusion is not necessarily important for binding to unfolded proteins,
      but its ATP-dependent conformational change mediates folding of captured unfolded
      proteins.

PMID- 14978027
TI  - RalA-exocyst interaction mediates GTP-dependent exocytosis.
AB  - Many secretory cells utilize a GTP-dependent pathway, in addition to the well
      characterized Ca2+-dependent pathway, to trigger exocytotic secretion. However,
      little is currently known about the mechanism by which this may occur. Here we
      show the key signaling pathway that mediates GTP-dependent exocytosis. Incubation
      of permeabilized PC12 cells with soluble RalA GTPase, but not RhoA or Rab3A
      GTPases, strongly inhibited GTP-dependent exocytosis. A Ral-binding fragment from
      Sec5, a component of the exocyst complex, showed a similar inhibition. Point
      mutations in both RalA (RalA(E38R)) and the Sec5 (Sec5(T11A)) fragment, which
      abolish RalA-Sec5 interaction also abolished the inhibition of GTP-dependent
      exocytosis. Moreover, transfection with wild-type RalA, but not RalA(E38R),
      enhanced GTP-dependent exocytosis. In contrast the RalA and the Sec5 fragment
      showed no inhibition of Ca2+-dependent exocytosis, but cleavage of a SNARE
      (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein
      by Botulinum neurotoxin blocked both GTP- and Ca2+-dependent exocytosis. Our
      results indicate that the interaction between RalA and the exocyst complex
      (containing Sec5) is essential for GTP-dependent exocytosis. Furthermore, GTP-
      and Ca2+-dependent exocytosis use different sensors and effectors for triggering
      exocytosis whereas their final fusion steps are both SNARE-dependent.

PMID- 14978028
TI  - BAG-1 proteins protect cardiac myocytes from simulated ischemia/reperfusion
      induced apoptosis via an alternate mechanism of cell survival independent of the
      proteasome.
AB  - BAG-1 (Bcl-2-associated athanogene-1) proteins interact with the HSC70 and HSP70
      heat shock proteins and have been proposed to promote cell survival by
      coordinating the function of these chaperones with the proteasome to facilitate
      protein degradation. Consistent with this proposal, previous analyses in cancer
      cells have demonstrated that BAG-1 requires protein domains important for
      HSC70/HSP70 and proteasome binding in order to interfere with the growth
      inhibition induced by heat shock (Townsend, P. A., Cutress, R. I., Sharp, A.,
      Brimmell, M., and Packham, G. (2003) Cancer Res., 63, 4150-4157). Moreover,
      cellular stress triggered the relocalization of the cytoplasmic BAG-1S
      (approximately 36 kDa) isoform to the nucleus, and both BAG-1S and the
      constitutively nuclear localized BAG-1L (approximately 50 kDa) isoform suppressed
      heat shock-induced apoptosis to the same extent, suggesting a critical role in
      the nucleus. Because ischemia (I) and reperfusion (R) are important stress
      signals in acute and chronic heart disease, we have examined the expression and
      function of BAG-1 proteins in primary cardiac myocytes (CMs) and the Langendorff
      perfused intact heart. The expression of both BAG-1 isoforms, BAG-1S and BAG-1L,
      was rapidly induced following ischemia in rat CM, and this was maintained during
      subsequent reperfusion. In control hearts, BAG-1S and BAG-1L were readily
      detectable in both the nucleus and the cytoplasm. However, BAG-1S did not
      relocate to the nucleus following simulated I/R. BAG-1 interacted with both RAF-1
      and HSC70 in CMs and the whole heart, and binding to HSC70 was increased
      following I/R. Overexpression of the human BAG-1S and BAG-1 M isoforms
      significantly reduced CM apoptosis following simulated I/R. By contrast, BAG-1L
      or BAG-1S fused to a heterologous nuclear localization sequence failed to protect
      CM. Finally, overexpression of BAG-1 deletion and point mutants unable to bind
      HSC70/HSP70 failed to offer cardioprotection. Surprisingly, a deletion mutant
      lacking the N-terminal ubiquitin-like domain, which mediates interaction with the
      proteasome, still promoted cardioprotection. Therefore, BAG-1 has a novel
      cardioprotective role, mediated via association with HSC70/HSP70, which is
      critical upon cytoplasmic localization but independent of the BAG-1 ubiquitin
      like domain. Our studies demonstrate that BAG-1 can influence cellular response
      to stress by multiple mechanisms, potentially influenced by the cell type and
      nature of the stress signal.

PMID- 14978029
TI  - Superoxide converts indigo carmine to isatin sulfonic acid: implications for the
      hypothesis that neutrophils produce ozone.
AB  - Recently, it was proposed that neutrophils generate ozone (Wentworth, P. J.,
      McDunn, J. E., Wentworth, A. D., Takeuchi, C., Nieva, J., Jones, T., Bautista,
      C., Ruedi, J. M., Gutierrez, A., Janda, K. D., Babior, B. M., Eschenmoser, A.,
      and Lerner, R. A. (2002) Science 298, 2195-2199; Babior, B. M., Takeuchi, C.,
      Ruedi, J., Gutierrez, A., and Wentworth, P. J. (2003) Proc. Natl. Acad. Sci. U.
      S. A. 100, 3031-3034). Evidence for the proposal was based largely on the
      chemistry of ozone reacting with indigo carmine to produce isatin sulfonic acid.
      In this investigation, we have examined the specificity of this reaction and
      whether it can be used as unequivocal evidence of ozone production by
      neutrophils. Stimulated neutrophils promoted the loss of indigo carmine and
      formation of isatin sulfonic acid in a reaction that was completely inhibited by
      superoxide dismutase. Methionine, which scavenges ozone, singlet oxygen, and
      hypochlorous acid, had no effect on the reaction. Neither did catalase or azide,
      which scavenge hydrogen peroxide and inhibit myeloperoxidase, respectively. From
      these results, it is apparent that superoxide was responsible for bleaching
      indigo carmine. Superoxide generated using xanthine oxidase and acetaldehyde also
      converted indigo carmine to isatin sulfonic acid in a reaction that was
      completely inhibited by superoxide dismutase and unaffected by catalase. When the
      xanthine oxidase reaction was carried out in H(2)(18)O, the proportion of (18)O
      incorporated into the isatin sulfonic acid was the same as that found for ozone.
      Thus, reactions of ozone and superoxide with indigo carmine are indistinguishable
      with respect to isatin sulfonic acid formation. We conclude that bleaching of
      indigo carmine cannot be used to invoke ozone production by neutrophils. Studies
      using indigo carmine to implicate ozone in other biological processes should also
      be interpreted with caution.

PMID- 14978030
TI  - PERK-dependent activation of Nrf2 contributes to redox homeostasis and cell
      survival following endoplasmic reticulum stress.
AB  - The accumulation of unfolded proteins elicits a cellular response that triggers
      both pro-survival and pro-apoptotic signaling events. PERK-dependent activation
      of NF-E2-related factor-2 (Nrf2) is critical for survival signaling during this
      response; however, the mechanism whereby Nrf2 confers a protective advantage to
      stressed cells remains to be defined. We now demonstrate that Nrf2 activation
      contributes to the maintenance of glutathione levels, which in turn functions as
      a buffer for the accumulation of reactive oxygen species during the unfolded
      protein response. The deleterious effects of Nrf2 or PERK deficiencies could be
      attenuated by the restoration of cellular glutathione levels or Nrf2 activity. In
      addition, the inhibition of reactive oxygen species production attenuated
      apoptotic induction following endoplasmic reticulum stress. Our data suggest that
      perturbations in cellular redox status sensitize cells to the harmful effects of
      endoplasmic reticulum stress, but that other factors are essential for apoptotic
      commitment.

PMID- 14978031
TI  - Differential expression and function of Tbx5 and Tbx20 in cardiac development.
AB  - The T-box transcription factors play critical roles in embryonic development
      including cell type specification, tissue patterning, and morphogenesis. Several
      T-box genes are expressed in the heart and are regulators of cardiac development.
      At the earliest stages of heart development, two of these genes, Tbx5 and Tbx20,
      are co-expressed in the heart-forming region but then become differentially
      expressed as heart morphogenesis progresses. Although Tbx5 and Tbx20 belong to
      the same gene family and share a highly conserved DNA-binding domain, their
      transcriptional activities are distinct. The C-terminal region of the Tbx5
      protein is a transcriptional activator, while the C terminus of Tbx20 can repress
      transcription. Tbx5, but not Tbx20, activates a cardiac-specific promoter (atrial
      natriuretic factor (ANF)) alone and synergistically with other transcription
      factors. In contrast, Tbx20 represses ANF promoter activity and also inhibits the
      activation mediated by Tbx5. Of the two T-box binding consensus sequences in the
      promoter of ANF, only T-box binding element 1 (TBE1) is required for the
      synergistic activation of ANF by Tbx5 and GATA4, but TBE2 is required for
      repression by Tbx20. To elucidate upstream signaling pathways that regulate Tbx5
      and Tbx20 expression, recombinant bone morphogenetic protein-2 was added to
      cardiogenic explants from chick embryos. Using real time reverse transcription
      PCR, it was demonstrated that Tbx20, but not Tbx5, is induced by bone
      morphogenetic protein-2. Collectively these data demonstrate clear differences in
      both the expression and function of two related transcription factors and suggest
      that the modulation of cardiac gene expression can occur as a result of
      combinatorial regulatory interactions of T-box proteins.

PMID- 14978032
TI  - Copper binding to the amyloid-beta (Abeta) peptide associated with Alzheimer's
      disease: folding, coordination geometry, pH dependence, stoichiometry, and
      affinity of Abeta-(1-28): insights from a range of complementary spectroscopic
      techniques.
AB  - There is now direct evidence that copper is bound to amyloid-beta peptide (Abeta)
      in senile plaque of Alzheimer's disease. Copper is also linked with the
      neurotoxicity of Abeta and free radical damage, and Cu(2+) chelators represent a
      possible therapy for Alzheimer's disease. We have therefore used a range of
      complementary spectroscopies to characterize the coordination of Cu(2+) to Abeta
      in solution. The mode of copper binding is highly pH-dependent. EPR spectroscopy
      indicates that both coppers have axial, Type II coordination geometry, square
      planar or square-pyramidal, with nitrogen and oxygen ligands. Circular dichroism
      studies indicate that copper chelation causes a structural transition of Abeta.
      Competition studies with glycine and l-histidine indicate that copper binds to
      Abeta-(1-28) at pH 7.4 with an affinity of K(a) approximately 10(7) m(-1). (1)H
      NMR indicates that histidine residues are involved in Cu(2+) coordination but
      that Tyr(10) is not. Studies using analogues of Abeta-(1-28) in which each of the
      histidine residues have been replaced by alanine or in which the N terminus is
      acetylated suggest that the N terminus and His(13) are crucial for Cu(2+) binding
      and that His(6) and His(14) are also implicated. Evidence for the link between
      Alzheimer's disease and Cu(2+) is growing, and our studies have made a
      significant contribution to understanding the mode of Cu(2+) binding to Abeta in
      solution.

PMID- 14978033
TI  - A polymorphic autoregulatory hormone response element in the human estrogen
      related receptor alpha (ERRalpha) promoter dictates peroxisome proliferator
      activated receptor gamma coactivator-1alpha control of ERRalpha expression.
AB  - The orphan nuclear estrogen-related receptor alpha (ERRalpha) and transcriptional
      cofactor peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC
      1alpha) are involved in the regulation of energy metabolism. Recently, extensive
      cross-talk between PGC-1alpha and ERRalpha has been demonstrated. The presence of
      PGC-1alpha is associated with an elevated expression of ERRalpha, and the two
      proteins can influence the transcriptional activities of one another. Using a
      candidate gene approach to detect regulatory variants within genes encoding
      nuclear receptors, we have identified a 23-bp sequence (ESRRA23) containing two
      nuclear receptor recognition half-site motifs that is present in 1-4 copies
      within the promoter of the human ESRRA gene encoding ERRalpha. The ESRRA23
      sequence contains a functional ERR response element that is specifically bound by
      ERRalpha, and chromatin immunoprecipitation shows that endogenous ERRalpha
      occupies its own promoter in vivo. Strikingly, introduction of PGC-1alpha in HeLa
      cells by transient transfection induces the activity of the ESRRA promoter in a
      manner that is dependent on the presence of the ESRRA23 element and on its
      dosage. Coexpression of ERRalpha and PGC-1alpha results in a synergistic
      activation of the ESRRA promoter. In experiments using ERRalpha null fibroblasts,
      the ability of PGC-1alpha to stimulate the ESRRA promoter is considerably reduced
      but can be restored by addition of ERRalpha. Taken together, these results
      demonstrate that an interdependent ERRalpha/PGC-1alpha-based transcriptional
      pathway targets the ESRRA23 element to dictate the level of ERRalpha expression.
      This study further suggests that this regulatory polymorphism may provide
      differential responses to ERRalpha/PGC-1alpha-mediated metabolic cues in the
      human population.

PMID- 14978034
TI  - The aryl hydrocarbon receptor (AhR) tyrosine 9, a residue that is essential for
      AhR DNA binding activity, is not a phosphoresidue but augments AhR
      phosphorylation.
AB  - We delineate a mechanism by which dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin or
      TCDD)-mediated formation of the aryl hydrocarbon receptor (AhR) DNA binding
      complex is disrupted by a single mutation at the conserved AhR tyrosine 9.
      Replacement of tyrosine 9 with the structurally conservative phenylalanine
      (AhRY9F) abolished binding to dioxin response element (DRE) D, E, and A and
      abrogated DRE-driven gene induction mediated by the AhR with no effect on TCDD
      binding, TCDD-induced nuclear localization, or ARNT heterodimerization. The
      speculated role for phosphorylation at tyrosine 9 was also examined. Anti
      phosphotyrosine immunoblotting could not detect a major difference between the
      AhRY9F mutant and wild-type AhR, but a basic isoelectric point shift was detected
      by two-dimensional gel electrophoresis of AhRY9F. However, an antibody raised to
      recognize only phosphorylated tyrosine 9 (anti-AhRpY9) confirmed that AhR
      tyrosine 9 is not a phosphorylated residue required for DRE binding. Kinase
      assays using synthetic peptides corresponding to the wild-type and mutant AhR
      residues 1-23 demonstrated that a tyrosine at position 9 is important for
      substrate recognition at serine(s)/threonine(s) within this sequence by purified
      protein kinase C (PKC). Also, compared with AhRY9F, immunopurified full-length
      wild-type receptor was more rapidly phosphorylated by PKC. Furthermore, co
      treatment of AhR-deficient cells that expressed AhRY9F and a DRE-driven
      luciferase construct with phorbol 12-myristate 13-acetate and TCDD resulted in a
      30% increase in luciferase activity compared with AhRY9F treated with TCDD alone.
      Overall, AhR tyrosine 9, which is not a phosphorylated residue itself but is
      required for DNA binding, appears to play a crucial role in AhR activity by
      permitting proper phosphorylation of the AhR.

PMID- 14978035
TI  - Induced autocrine signaling through the epidermal growth factor receptor
      contributes to the response of mammary epithelial cells to tumor necrosis factor
      alpha.
AB  - In contrast to the well known cytotoxic effects of tumor necrosis factor (TNF)
      alpha in many mammary cancer cells, we have found that TNF stimulates the
      proliferation and motility of human mammary epithelial cells (HMECs). Since the
      response of HMECs to TNF is similar to effects mediated by epidermal growth
      factor receptor (EGFR) activation, we explored the potential role of cross-talk
      through the EGFR signaling pathways in mediating cellular responses to TNF. Using
      a microarray enzyme-linked immunoassay, we found that exposure to TNF stimulated
      the dose-dependent shedding of the EGFR ligand transforming growth factor alpha
      (TGFalpha). Both proliferation and motility of HMECs induced by TNF was prevented
      either by inhibiting membrane protein shedding with a metalloprotease inhibitor,
      by blocking epidermal growth factor receptor (EGFR) kinase activity, or by
      limiting ligand-receptor interactions with an antagonistic anti-EGFR antibody.
      EGFR activity was also necessary for TNF-induced release of matrix
      metalloprotease-9, thought to be an essential regulator of mammary cell
      migration. The cellular response to TNF was associated with a biphasic temporal
      pattern of extracellular signal-regulated kinase (ERK) phosphorylation, which was
      EGFR-dependent and modulated by inhibition of metalloprotease-mediated shedding.
      Significantly, the late phase of ERK phosphorylation, detectable within 4 h after
      exposure, was blocked by the metalloprotease inhibitor batimastat, indicating
      that autocrine signaling through ligand shedding was responsible for this
      secondary wave of ERK activity. Our results indicate a novel and important role
      for metalloprotease activation and EGFR transmodulation in mediating the cellular
      response to TNF.

PMID- 14978036
TI  - Origin of cooperativity in the activation of fructose-1,6-bisphosphatase by Mg2+.
AB  - Fructose-1,6-bisphosphatase requires a divalent metal cation for catalysis,
      Mg(2+) being its most studied activator. Phosphatase activity increases
      sigmoidally with the concentration of Mg(2+), but the mechanistic basis for such
      cooperativity is unknown. Bound magnesium cations can interact within a single
      subunit or between different subunits of the enzyme tetramer. Mutations of
      Asp(118), Asp(121), or Glu(97) to alanine inactivate the recombinant porcine
      enzyme. These residues bind directly to magnesium cations at the active site.
      Three different hybrid tetramers of fructose-1,6-bisphosphatase, composed of one
      wild-type subunit and three subunits bearing one of the mutations above, exhibit
      kinetic parameters (K(m) for fructose-1,6-bisphosphate, 1.1-1.8 microm; K(a) for
      Mg(2+), 0.34-0.76 mm; K(i) for fructose-2,6-bisphosphate, 0.11-0.61 microm; and
      IC(50) for AMP, 3.8-7.4 microm) nearly identical to those of the wild-type
      enzyme. Notwithstanding these similarities, the k(cat) parameter for each hybrid
      tetramer is approximately one-fourth of that for the wild-type enzyme. Evidently,
      each subunit in the wild-type tetramer can independently achieve maximum velocity
      when activated by Mg(2+). Moreover, the activities of the three hybrid tetramers
      vary sigmoidally with the concentration of Mg(2+) (Hill coefficients of
      approximately 2). The findings above are fully consistent with a mechanism of
      cooperativity that arises from within a single subunit of fructose-1,6
      bisphosphatase.

PMID- 14978037
TI  - Evidence for a serum factor that initiates the re-calcification of demineralized
      bone.
AB  - The present studies show for the first time that demineralized bone re-calcifies
      rapidly when incubated at 37 degrees C in rat serum: re-calcification can be
      demonstrated by Alizarin Red and von Kossa stains, by depletion of serum calcium,
      and by uptake of calcium and phosphate by bone matrix. Re-calcification is
      specific for the type I collagen matrix structures that were calcified in the
      original bone, with no evidence for calcification in periosteum or cartilage. Re
      calcification ceases when the amount of calcium and phosphate introduced into the
      matrix is comparable to that present in the original bone prior to
      demineralization, and the re-calcified bone is palpably hard. Re-calcified bone
      mineral is comparable to the original bone mineral in calcium to phosphate ratio
      and in Fourier transform infrared and x-ray diffraction spectra. The serum
      activity responsible for re-calcification is sufficiently potent that the
      addition of only 1.5% serum to Dulbecco's modified Eagle's medium causes bone re
      calcification. This putative serum calcification factor has an apparent molecular
      mass of 55-150 kDa and is inactivated by trypsin or chymotrypsin. The serum
      calcification factor must act on bone for 12 h before re-calcification can be
      detected by Alizarin Red or von Kossa staining and before the subsequent growth
      of calcification will occur in the absence of serum. The speed, matrix-type
      specificity, and extent of the serum-induced re-calcification of demineralized
      bone suggest that the serum calcification factor identified in these studies may
      participate in the normal calcification of bone.

PMID- 14978038
TI  - Functional domain mapping and selective trans-dominant effects exhibited by Cx26
      disease-causing mutations.
AB  - Mutations in Cx26 are a major cause of autosomal dominant and recessive forms of
      sensorineural deafness. Some mutations in Cx26 are associated not only with
      deafness but also with skin disease. We examined the subcellular localization and
      function of two green fluorescent protein (GFP)-tagged Cx26 point mutants that
      exhibit both phenotypes, G59A-GFP and D66H-GFP. D66H-GFP was retained within the
      brefeldin A-insensitive trans-Golgi network, whereas a population of G59A-GFP was
      transported to the cell surface. Neither G59A nor D66H formed gap junctions that
      were permeable to small fluorescent dyes, suggesting they are loss-of-function
      mutations. When co-expressed with wild-type Cx26, both G59A and D66H exerted
      dominant-negative effects on Cx26 function. G59A also exerted a trans-dominant
      negative effect on co-expressed wild type Cx32 and Cx43, whereas D66H exerted a
      trans-dominant negative effect on Cx43 but not Cx32. We propose that the severity
      of the skin disease is dependent on the specific nature of the Cx26 mutation and
      the trans-dominant selectivity of the Cx26 mutants on co-expressed connexins.
      Additional systematic mutations at residue D66, in which the overall charge of
      this motif was altered, suggested that the first extracellular loop is critical
      for Cx26 transport to the cell surface as well as function of the resulting gap
      junction channels.

PMID- 14978039
TI  - Biogenesis of the protein import channel Tom40 of the mitochondrial outer
      membrane: intermembrane space components are involved in an early stage of the
      assembly pathway.
AB  - Tom40 forms the central channel of the preprotein translocase of the
      mitochondrial outer membrane (TOM complex). The precursor of Tom40 is encoded in
      the nucleus, synthesized in the cytosol, and imported into mitochondria via a
      multi-step assembly pathway that involves the mature TOM complex and the sorting
      and assembly machinery of the outer membrane (SAM complex). We report that
      opening of the mitochondrial intermembrane space by swelling blocks the assembly
      pathway of the beta-barrel protein Tom40. Mitochondria with defects in small Tim
      proteins of the intermembrane space are impaired in the Tom40 assembly pathway.
      Swelling as well as defects in the small Tim proteins inhibit an early stage of
      the Tom40 import pathway that is needed for formation of a Tom40-SAM
      intermediate. We propose that the biogenesis pathway of beta-barrel proteins of
      the outer mitochondrial membrane not only requires TOM and SAM components, but
      also involves components of the intermembrane space.

PMID- 14978040
TI  - NEK2A interacts with MAD1 and possibly functions as a novel integrator of the
      spindle checkpoint signaling.
AB  - Chromosome segregation in mitosis is orchestrated by protein kinase signaling
      cascades. A biochemical cascade named spindle checkpoint ensures the spatial and
      temporal order of chromosome segregation during mitosis. Here we report that
      spindle checkpoint protein MAD1 interacts with NEK2A, a human orthologue of the
      Aspergillus nidulans NIMA kinase. MAD1 interacts with NEK2A in vitro and in vivo
      via a leucine zipper-containing domain located at the C terminus of MAD1. Like
      MAD1, NEK2A is localized to HeLa cell kinetochore of mitotic cells. Elimination
      of NEK2A by small interfering RNA does not arrest cells in mitosis but causes
      aberrant premature chromosome segregation. NEK2A is required for MAD2 but not
      MAD1, BUB1, and HEC1 to associate with kinetochores. These NEK2A-eliminated or 
      suppressed cells display a chromosome bridge phenotype with sister chromatid
      inter-connected. Moreover, loss of NEK2A impairs mitotic checkpoint signaling in
      response to spindle damage by nocodazole, which affected mitotic escape and led
      to generation of cells with multiple nuclei. Our data demonstrate that NEK2A is a
      kinetochore-associated protein kinase essential for faithful chromosome
      segregation. We hypothesize that NEK2A links MAD2 molecular dynamics to spindle
      checkpoint signaling.

PMID- 14978041
TI  - Alternatively spliced soluble coxsackie-adenovirus receptors inhibit
      coxsackievirus infection.
AB  - The coxsackie-adenovirus receptor (CAR) is a transmembrane receptor of the
      immunoglobulin superfamily whose expression is altered in myocardial and
      malignant diseases. Soluble isoforms of other adhesion molecules and cytokine
      receptors have been proven to have significant agonist and antagonist effects on
      their full-length receptors; however, little is known about soluble CAR
      receptors. Using reverse transcription-PCR, we identified three CAR isoforms that
      lack the transmembrane domain and are the result of alternative RNA splicing
      events between exons IV and VII (CAR4/7), exons III and VII (CAR3/7), and exons
      II and VII (CAR2/7). The three CAR isoforms contain different regions of the
      extracellular domain of CAR and have C termini that are distinct from the full
      length receptors. These alternatively spliced CAR proteins are released from
      transfected HeLa cells confirming that they are soluble proteins. In addition,
      the soluble CAR proteins are able to interact with the bacterially expressed
      extracellular domain of CAR. In addition, CAR4/7 but not CAR2/7 was found to bind
      to coxsackievirus B3 (CVB3). Each of the three soluble CAR isoforms is able to
      inhibit CVB3 infection of transfected HeLa cells. Given that soluble CAR isoforms
      can bind to the extracellular domain of CAR and the CVB3 capsid, they may have
      significant inhibitory or stimulatory effects on CAR signaling and may have an
      important role in the host defense against viral infection.

PMID- 14978042
TI  - Single-stranded breaks in DNA but not oxidative DNA base damages block
      transcriptional elongation by RNA polymerase II in HeLa cell nuclear extracts.
AB  - Transcription and repair of many DNA helix-distorting lesions such as cyclobutane
      pyrimidine dimers have been shown to be coupled in cells across phyla from
      bacteria to humans. The signal for transcription-coupled repair appears to be a
      stalled transcription complex at the lesion site. To determine whether oxidative
      DNA lesions can block correctly initiated human RNA polymerase II, we examined
      the effect of site-specifically introduced oxidative damages on transcription in
      HeLa cell nuclear extracts. We found that transcription was blocked by single
      stranded breaks, common oxidative DNA lesions, when present in the transcribed
      strand of the transcription template. Cyclobutane pyrimidine dimers, which have
      been previously shown to block transcription both in vitro and in vivo, also
      blocked transcription in the HeLa cell nuclear transcription assay. In contrast,
      the oxidative DNA base lesions, 8-oxoguanine, 5-hydroxycytosine, and thymine
      glycol did not inhibit transcription, although pausing was observed with the
      thymine glycol lesion. Thus, DNA strand breaks but not oxidative DNA base damages
      blocked transcription by RNA polymerase II.

PMID- 14978043
TI  - Crl, a low temperature-induced protein in Escherichia coli that binds directly to
      the stationary phase sigma subunit of RNA polymerase.
AB  - The alternative sigma factor sigma(S) (RpoS) of Escherichia coli RNA polymerase
      regulates the expression of stationary phase and stress-response genes. sigma(S)
      is also required for the transcription of the cryptic genes csgBA that encode the
      subunits of the curli proteins. The expression of the csgBA genes is regulated in
      response to a multitude of physiological signals. In stationary phase, these
      genes are transcribed by the sigma(S) factor, and expression of the operon is
      enhanced by the small protein Crl. It has been shown that Crl stimulates the
      activity of sigma(S), leading to an increased transcription rate of a subset of
      genes of the rpoS regulon in stationary phase. However, the underlying molecular
      mechanism has remained elusive. We show here that Crl interacts directly with
      sigma(S) and that this interaction promotes binding of the sigma(S) holoenzyme
      (Esigma(S)) to the csgBA promoter. Expression of Crl is increased during the
      transition from growing to stationary phase. Crl accumulates in stationary phase
      cells at low temperature (30 degrees C) but not at 37 degrees C. We therefore
      propose that Crl is a second thermosensor, besides DsrA, controlling sigma(S)
      activity.

PMID- 14978044
TI  - Substitutions in an active site loop of Escherichia coli IscS result in specific
      defects in Fe-S cluster and thionucleoside biosynthesis in vivo.
AB  - IscS catalyzes the fragmentation of l-cysteine to l-alanine and sulfane sulfur in
      the form of a cysteine persulfide in the active site of the enzyme. In
      Escherichia coli IscS, the active site cysteine Cys(328) resides in a flexible
      loop that potentially influences both the formation and stability of the cysteine
      persulfide as well as the specificity of sulfur transfer to protein substrates.
      Alanine-scanning substitution of this 14 amino acid region surrounding Cys(328)
      identified additional residues important for IscS function in vivo. Two
      mutations, S326A and L333A, resulted in strains that were severely impaired in Fe
      S cluster synthesis in vivo. The mutant strains were deficient in Fe-S cluster
      dependent tRNA thionucleosides (s(2)C and ms(2)i(6)A) yet showed wild type levels
      of Fe-S-independent thionucleosides (s(4)U and mnm(5)s(2)U) that require
      persulfide formation and transfer. In vitro, the mutant proteins were similar to
      wild type in both cysteine desulfurase activity and sulfur transfer to IscU.
      These results indicate that residues in the active site loop can selectively
      affect Fe-S cluster biosynthesis in vivo without detectably affecting persulfide
      delivery and suggest that additional assays may be necessary to fully represent
      the functions of IscS in Fe-S cluster formation.

PMID- 14978045
TI  - DNA methylation-mediated control of Sry gene expression in mouse gonadal
      development.
AB  - DNA methylation at CpG sequences is involved in tissue-specific and
      developmentally regulated gene expression. The Sry (sex-determining region on the
      Y chromosome) gene encodes a master protein for initiating testis differentiation
      in mammals, and its expression is restricted to gonadal somatic cells at 10.5
      12.5 days post-coitum (dpc) in the mouse. We found that in vitro methylation of
      the 5'-flanking region of the Sry gene caused suppression of reporter activity,
      implying that Sry gene expression could be regulated by DNA methylation-mediated
      gene silencing. Bisulfite restriction mapping and sodium bisulfite sequencing
      revealed that the 5'-flanking region of the Sry gene was hypermethylated in the
      8.5-dpc embryos in which the Sry gene was not expressed. Importantly, this region
      was specifically hypomethylated in the gonad at 11.5 dpc, while the
      hypermethylated status was maintained in tissues that do not express the Sry
      gene. We concluded that expression of the Sry gene is under the control of an
      epigenetic mechanism mediated by DNA methylation.

PMID- 14978049
TI  - Force production and flow structure of the leading edge vortex on flapping wings
      at high and low Reynolds numbers.
AB  - The elevated aerodynamic performance of insects has been attributed in part to
      the generation and maintenance of a stable region of vorticity known as the
      leading edge vortex (LEV). One explanation for the stability of the LEV is that
      spiraling axial flow within the vortex core drains energy into the tip vortex,
      forming a leading-edge spiral vortex analogous to the flow structure generated by
      delta wing aircraft. However, whereas spiral flow is a conspicuous feature of
      flapping wings at Reynolds numbers (Re) of 5000, similar experiments at Re=100
      failed to identify a comparable structure. We used a dynamically scaled robot to
      investigate both the forces and the flows created by a wing undergoing identical
      motion at Re of approximately 120 and approximately 1400. In both cases, motion
      at constant angular velocity and fixed angle of attack generated a stable LEV
      with no evidence of shedding. At Re=1400, flow visualization indicated an intense
      narrow region of spanwise flow within the core of the LEV, a feature
      conspicuously absent at Re=120. The results suggest that the transport of
      vorticity from the leading edge to the wake that permits prolonged vortex
      attachment takes different forms at different Re.

PMID- 14978050
TI  - Central control of electric signaling behavior in the mormyrid Brienomyrus
      brachyistius: segregation of behavior-specific inputs and the role of modifiable
      recurrent inhibition.
AB  - Like all mormyrid fish, Brienomyrus brachyistius produces an electric organ
      discharge (EOD) with a constant waveform and variable sequence of pulse intervals
      (SPI). Periodic bursts fall into two display categories termed 'scallops' and
      'accelerations', with a third category termed 'rasps' that appears to combine the
      two. The medullary EOD command nucleus (CN) receives excitatory input from the
      midbrain precommand nucleus (PCN) and the thalamic dorsal posterior nucleus (DP),
      both of which are regulated by a recurrent inhibitory projection from the
      ventroposterior nucleus of the torus semicircularis (VP). We tested the following
      hypotheses: (1) PCN and DP are responsible for generating different burst types
      (scallops and accelerations, respectively), (2) differences in the strength of
      recurrent inhibition are related to physiological differences between PCN and DP
      and (3) recurrent inhibition regulates the resting electromotor rhythm, while
      disinhibition releases PCN and DP, allowing them to generate bursts.
      Iontophoresis of the excitatory neurotransmitter L-glutamate (L-Glu) into DP led
      to acceleration-like output patterns, while in PCN it led to scallop-like output
      patterns. Iontophoresis of the inhibitory neurotransmitter gamma-amino-butyric
      acid (GABA) into DP and PCN led to an elongation of intervals, as did
      iontophoresis of L-Glu into VP. Iontophoresis of the GABA(A) receptor blocker
      bicuculline methiodide (BMI) into DP and PCN induced repetitive bursting behavior
      and eliminated differences in the effects of L-Glu iontophoresis in the two
      nuclei. These results support our three hypotheses, suggesting that production of
      different communication behaviors may be regulated by spatially distinct groups
      of neurons, and recurrent inhibition and disinhibition may play an active role in
      driving and shaping such behaviors.

PMID- 14978051
TI  - Does she smell like a queen? Chemoreception of a cuticular hydrocarbon signal in
      the ant Pachycondyla inversa.
AB  - Primitive ant societies, with their relatively simple social structure, provide
      an opportunity to explore the evolution of chemical communication, in particular
      of mechanisms underlying within-colony discrimination. In the same colony, slight
      differences in individual odours can be the basis for discrimination between
      different castes, classes of age and social status. There is some evidence from
      correlative studies that such inter-individual variation is associated with
      differences in reproductive status, but direct proof that certain chemical
      compounds are detected and recognized by ants is still lacking. In the ponerine
      ant Pachycondyla inversa, fertile queens and, in orphaned colonies, dominant egg
      laying workers are characterized by the predominance of a branched hydrocarbon,
      3,11-dimethylheptacosane (3,11-diMeC(27)) on the cuticle. Using
      electroanntennography and gas chromatography with electroantennographic
      detection, we show that the antennae of P. inversa workers react to this key
      compound. 3,11-diMeC(27) is correlated with ovarian activity and, because it is
      detected, is likely to assume the role of a fertility signal reflecting the
      quality of the sender.

PMID- 14978052
TI  - Intracellular calcium translocation during the contraction-relaxation cycle in
      scorpionfish swimbladder muscle.
AB  - To examine intracellular Ca(2+) translocation during the contraction-relaxation
      cycle in vertebrate striated muscle, electron probe X-ray microanalysis was
      performed on the swimbladder muscle (SBM) fibres of a scorpionfish Sebastiscus
      marmoratus. The SBM fibres were rapidly frozen at rest, during contraction and at
      various times after the onset of relaxation. Changes in calcium distribution in
      the components of the sarcoplasmic reticulum (SR) were examined on the SBM fibre
      cryosections. In resting fibres, the calcium concentration was highest around the
      boundary between the A and I bands (A-I boundary), where the terminal cisternae
      (TC) were located. In contracting fibres, the calcium concentration decreased
      around the A-I boundary, while it increased in all other regions of the
      sarcomere, indicating Ca(2+) release from the TC into the myoplasm. During
      relaxation, the calcium concentration first increased around the regions, where
      the fenestrated collars (FC) and the longitudinal tubules (LT) were located, and
      then gradually returned to the levels seen in resting fibres. These results
      support the view that, after the onset of relaxation in the SBM fibres, Ca(2+) in
      the myoplasm is first taken up by the FC and the LT, and then gradually returns
      to the TC.

PMID- 14978053
TI  - Stimulation by cadmium of myohemerythrin-like cells in the gut of the annelid
      Nereis diversicolor.
AB  - Isolated guts of Nereis diversicolor revealed the existence of a cadmium-binding
      protein, the MPII, belonging to the group of hemerythrins and myohemerythrins.
      The presence of MPII in the cells of the intestine was demonstrated by
      immunocytochemistry, using anti-MPII, a monoclonal antibody. In addition, using
      in situ hybridization and northern blotting, it was shown that MPII-cells are the
      site of synthesis of this molecule. Exposure of the worms to cadmium led to the
      cellular activation process of MPII-cells (i.e. transformation of the nucleolus,
      development of the endoplasmic reticulum and the Golgi apparatus), although MPII
      mRNA transcript levels were unchanged. Enzyme-linked immunosorbent assay (ELISA)
      of gut extracts revealed that MPII levels were increased after exposure to Cd, so
      it appears that this protein is synthesized as a response to Cd exposure without
      any new synthesis of mRNA. This mechanism of regulation is quite similar to that
      reported in the case of mammalian ferritin and may be involved in the regulation
      of Cd levels in this worm.

PMID- 14978054
TI  - Mechanisms and significance of reduced activity and responsiveness in resting
      frog tadpoles.
AB  - Hatchling Xenopus laevis tadpoles spend most of their time attached to objects or
      the water surface by mucus secreted by a gland on the head. While attached,
      swimming activity and responsiveness to swim-initiating stimuli are reduced over
      long periods of time. We have investigated the mechanisms and significance of
      this apparent long-term inhibition. In behavioural experiments we show, firstly,
      that innervation of the cement gland and GABA(A)-mediated inhibition are
      necessary for attachment to reduce responsiveness, and secondly, that denervation
      of the cement gland increases tadpole activity and increases their predation by
      damselfly nymphs (Zygoptera). To investigate the neuronal pathway from the cement
      gland to GABA(A) inhibition, we have devised an immobilized, inverted tadpole
      preparation where a weight attached to the mucus simulates the force as it hangs.
      Simulated attachment reduces responsiveness and spontaneous fictive swimming
      activity. We have recorded the activity and responses of trigeminal neurons
      innervating the cement gland. They are spontaneously active and simulating
      attachment results in a sustained increase in this activity. We propose that
      hanging from a mucus strand increases firing in cement gland afferents. This
      leads to tonic GABA inhibition that reduces tadpole activity and responses, and
      leads to fewer attacks by predators.

PMID- 14978055
TI  - The effect of molluscan glue proteins on gel mechanics.
AB  - Several molluscs have been shown to alternate between a non-adhesive trail mucus
      and a similar gel that forms a strong glue. The major structural difference
      between the two secretions is the presence of specific proteins in the adhesive
      mucus. The present study identifies similar proteins from the glue of the slug
      Arion subfuscus and the land snail Helix aspersa. To investigate the role played
      by these proteins in adhesion, the proteins were isolated from the adhesive mucus
      of different molluscs and added to commercial polymer solutions. The effect was
      observed qualitatively, and quantified using a dynamic rheometer. The isolated
      proteins triggered gelling or visible stiffening of agar, pectin and
      polygalacturonic acid. The effect was stronger on more negatively charged
      polymers. The effect of the proteins was concentration dependent with an optimal
      concentration of 1-1.5 mg ml(-1), and was weakened when their structure changed.
      Other proteins and carbohydrates found in the adhesive mucus had no clear
      mechanical effect on gels. These findings show that the addition of these
      proteins to large, anionic polymers plays a central role in the formation of a
      glue from a mucus-like secretion. Such a mechanism may be common among
      invertebrates, and it may guide biomimetic approaches in the development of glues
      and gels.

PMID- 14978056
TI  - Unsteady aerodynamic forces of a flapping wing.
AB  - The unsteady aerodynamic forces of a model fruit fly wing in flapping motion were
      investigated by numerically solving the Navier-Stokes equations. The flapping
      motion consisted of translation and rotation [the translation velocity (u(t))
      varied according to the simple harmonic function (SHF), and the rotation was
      confined to a short period around stroke reversal]. First, it was shown that for
      a wing of given geometry with u(t) varying as the SHF, the aerodynamic force
      coefficients depended only on five non-dimensional parameters, i.e. Reynolds
      number (Re), stroke amplitude (Phi), mid-stroke angle of attack (alpha(m)), non
      dimensional duration of wing rotation (Delta tau(r)) and rotation timing [the
      mean translation velocity at radius of the second moment of wing area (U), the
      mean chord length (c) and c/U were used as reference velocity, length and time,
      respectively]. Next, the force coefficients were investigated for a case in which
      typical values of these parameters were used (Re=200; Phi=150 degrees;
      alpha(m)=40 degrees; Delta tau(r) was 20% of wingbeat period; rotation was
      symmetrical). Finally, the effects of varying these parameters on the force
      coefficients were investigated. In the Re range considered (20-1800), when Re was
      above approximately 100, the lift ((L)) and drag ((D)) coefficients were large
      and varied only slightly with Re (in agreement with results previously published
      for revolving wings); the large force coefficients were mainly due to the delayed
      stall mechanism. However, when Re was below approximately 100, (L) decreased and
      (D) increased greatly. At such low Re, similar to the case of higher Re, the
      leading edge vortex existed and attached to the wing in the translatory phase of
      a half-stroke; but it was very weak and its vorticity rather diffused, resulting
      in the small (L) and large (D). Comparison of the calculated results with
      available hovering flight data in eight species (Re ranging from 13 to 1500)
      showed that when Re was above approximately 100, lift equal to insect weight
      could be produced but when Re was lower than approximately 100, additional high
      lift mechanisms were needed. In the range of Re above approximately 100, Phi from
      90 degrees to 180 degrees and Delta tau(r) from 17% to 32% of the stroke period
      (symmetrical rotation), the force coefficients varied only slightly with Re, Phi
      and Delta tau(r). This meant that the forces were approximately proportional to
      the square of Phi n (n is the wingbeat frequency); thus, changing Phi and/or n
      could effectively control the magnitude of the total aerodynamic force. The time
      course of (L) (or (D)) in a half-stroke for u(t) varying according to the SHF
      resembled a half sine-wave. It was considerably different from that published
      previously for u(t), varying according to a trapezoidal function (TF) with large
      accelerations at stroke reversal, which was characterized by large peaks at the
      beginning and near the end of the half-stroke. However, the mean force
      coefficients and the mechanical power were not so different between these two
      cases (e.g. the mean force coefficients for u(t) varying as the TF were
      approximately 10% smaller than those for u(t) varying as the SHF except when wing
      rotation is delayed).

PMID- 14978057
TI  - Overexpression of broad: a new insight into its role in the Drosophila
      prothoracic gland cells.
AB  - Insect molting is triggered by ecdysteroids, which are produced in the
      prothoracic glands (PG). The broad (br) gene is one of the 'early genes' directly
      regulated by ecdysteroids. Ectopic expression of the BR-Z3 isoform in early
      second instar Drosophila larvae (L2) before the rise of the ecdysteroid titer
      prevented molting to the third instar, but the larvae subsequently formed L2
      prepupae after prolonged feeding. When these larvae were fed on diet containing
      20-hydroxyecdysone (20E), they formed pharate third instar larvae. The critical
      weight for normal L3 pupariation of w(1118) larvae was found to be 0.8 mg and
      that for L2 pupariation was 0.45 mg. We also defined a threshold weight for
      metamorphosis of 0.3 mg, above which L2 larvae will metamorphose when provided
      with 20E. BR-Z3 apparently works through the PG cells of the ring gland but not
      the putative neurosecretory cells that drive ecdysone secretion, because ectopic
      expression of BR-Z3 specifically in the ring gland caused 53% of the larvae to
      become permanent first instar larvae. Driving other BR isoforms in the ring gland
      prevented larval molting or pupariation to varying degrees. These molting defects
      were rescued by feeding 20E. Overexpression of each of the BR isoforms caused
      degeneration of the PG cells but on different time courses, indicating that BR is
      a signal for the degeneration of the PG cells that normally occurs during the
      pupal-adult transition.

PMID- 14978058
TI  - The anterior cardiac plexus: an intrinsic neurosecretory site within the
      stomatogastric nervous system of the crab Cancer productus.
AB  - The stomatogastric nervous system (STNS) of decapod crustaceans is modulated by
      both locally released and circulating substances. In some species, including
      chelate lobsters and freshwater crayfish, the release zones for hormones are
      located both intrinsically to and at some distance from the STNS. In other
      crustaceans, including Brachyuran crabs, the existence of extrinsic sites is well
      documented. Little, however, is known about the presence of intrinsic
      neuroendocrine structures in these animals. Putative intrinsic sites have been
      identified within the STNS of several crab species, though ultrastructural
      confirmation that these structures are in fact neuroendocrine in nature remains
      lacking. Using a combination of anatomical techniques, we demonstrate the
      existence of a pair of neurosecretory sites within the STNS of the crab Cancer
      productus. These structures, which we have named the anterior cardiac plexi
      (ACPs), are located on the anterior cardiac nerves (acns), which overlie the
      cardiac sac region of the foregut. Each ACP starts several hundred micro m from
      the origin of the acn and extends distally for up to several mm. Transmission
      electron microscopy done on these structures shows that nerve terminals are
      present in the peripheral portion of each acn, just below a well defined
      epineurium. These terminals contain dense-core and, occasionally, electron-lucent
      vesicles. In many terminals, morphological correlates of hormone secretion are
      evident. Immunocytochemistry shows that the ACPs are immunopositive for FLRFamide
      related peptide. All FLRFamide labeling in the ACPs originates from four axons,
      which descend to these sites through the superior oesophageal and stomatogastric
      nerves. Moreover, these FLRFamide-immunopositive axons are the sole source of
      innervation to the ACPs. Collectively, our results suggest that the STNS of C.
      productus is not only a potential target site for circulating hormones, but also
      serves as a neuroendocrine release center itself.

PMID- 14978059
TI  - Locomotor performance of closely related Tropidurus species: relationships with
      physiological parameters and ecological divergence.
AB  - Tropidurid lizards have colonized a variety of Brazilian open environments
      without remarkable morphological variation, despite ecological and structural
      differences among habitats used. This study focuses on two Tropidurus sister
      species that, despite systematic proximity and similar morphology, exhibit great
      ecological divergence and a third ecologically generalist congeneric species
      providing an outgroup comparison. We quantified jumping capacity and sprint speed
      of each species on sand and rock to test whether ecological divergence was also
      accompanied by differences in locomotor performance. Relevant physiological
      traits possibly associated with locomotor performance - metabolic scopes and
      fiber type composition, power output and activity of the enzymes citrate
      synthase, pyruvate kinase and lactate dehydrogenase of the iliofibularis muscle -
      were also compared among the three Tropidurus species. We found that the two
      sister-species exhibited remarkable differences in jumping performance, while
      Tropidurus oreadicus, the more distantly related species, exhibited intermediate
      values. Tropidurus psamonastes, a species endemic to sand dunes, exhibited high
      absolute sprint speeds on sand, jumped rarely and possessed a high proportion of
      glycolytic fibers and low activity of citrate synthase. The sister-species
      Tropidurus itambere, endemic to rocky outcrops, performed a large number of jumps
      and achieved lower absolute sprint speed than T. psamonastes. This study provides
      evidence of rapid divergence of locomotor parameters between sister-species that
      use different substrates, which is only partially explained by variation in
      physiological parameters of the iliofibularis muscle.

PMID- 14978060
TI  - Light-dependent magnetoreception in birds: analysis of the behaviour under red
      light after pre-exposure to red light.
AB  - In previous experiments, migratory birds had been disoriented under 635 nm red
      light, apparently unable to use their magnetic compass. The present study with
      European robins, Erithacus rubecula, confirms these findings for red light at the
      levels of 6 x 10(15) quanta s(-1) m(-2) and 43 x 10(15) quanta s(-1) m(-2),
      suggesting that the disorientation under red light was not caused by the test
      light being below the threshold for magnetoreception. However, pre-exposure to
      red light for 1 h immediately before the critical tests under red light of 6-7 x
      10(15) quanta s(-1) m(-2) enabled robins to orient in their seasonally
      appropriate migratory direction in spring as well as in autumn. Pre-exposure to
      darkness, by contrast, failed to induce orientation under red light. Under green
      light of 7 x 10(15) quanta s(-1) m(-2), the birds were oriented in their
      migratory orientation after both types of pre-exposure. These findings suggest
      that the newly gained ability to orient under red light might be based on
      learning to interpret a novel pattern of activation of the magnetoreceptors and
      hence may represent a parallel to the previously described enlargement of the
      functional window to new magnetic intensities. Mechanisms involving two types of
      spectral mechanisms with different absorbance maxima and their possible
      interactions are discussed.

PMID- 14978061
TI  - Measurement of cell velocity distributions in populations of motile algae.
AB  - The self-propulsion of unicellular algae in still ambient fluid is studied using
      a previously reported laser-based tracking method, supplemented by new tracking
      software. A few hundred swimming cells are observed simultaneously and the
      average parameters of the cells' motility are calculated. The time-dependent, two
      dimensional distribution of swimming velocities is measured and the three
      dimensional distribution is recovered by assuming horizontal isotropy. The mean
      and variance of the cell turning angle are quantified, to estimate the
      reorientation time and rotational diffusivity of the bottom-heavy cell. The
      cells' phototactic and photokinetic responses to the laser light are evaluated.
      The results are generally consistent both with earlier assumptions about the
      nature of cell swimming and quantitative measurements, appropriately adjusted.
      The laser-based tracking method, which makes it possible to average over a large
      number of motile objects, is shown to be a powerful tool for the study of
      microorganism motility.

PMID- 14978062
TI  - Isolation of a novel aquaglyceroporin from a marine teleost (Sparus auratus):
      function and tissue distribution.
AB  - The aquaporins (formerly called the major intrinsic protein family) are
      transmembrane channel proteins. The family includes the CHIP group, which are
      functionally characterised as water channels and the GLP group, which are
      specialised for glycerol transport. The present study reports the identification
      and characterisation of a novel GLP family member in a teleost fish, the sea
      bream Sparus auratus. A sea bream aquaporin (sbAQP) cDNA of 1047 bp and encoding
      a protein of 298 amino acids was isolated from a kidney cDNA library. Functional
      characterization of the sbAQP using a Xenopus oocyte assay revealed that the
      isolated cDNA stimulated osmotic water permeability in a mercury-sensitive manner
      and also stimulated urea and glycerol uptake. Northern blotting demonstrated that
      sbAQP was expressed at high levels in the posterior region of the gut, where two
      transcripts were identified (1.6 kb and 2 kb), and in kidney, where a single
      transcript was present (2 kb). In situ hybridisation studies with a sbAQP
      riboprobe revealed its presence in the lamina propria and smooth muscle layer of
      the posterior region of the gut and in epithelial cells of some kidney tubules.
      sbAQP was also present in putative chloride cells of the gill. Phylogenetic
      analysis of sbAQP, including putative GLP genes from Fugu rubripes, revealed that
      it did not group with any of the previously isolated vertebrate GLPs and instead
      formed a separate group, suggesting that it may be a novel GLP member.

PMID- 14978063
TI  - Microspectrophotometry of visual pigments and oil droplets in a marine bird, the
      wedge-tailed shearwater Puffinus pacificus: topographic variations in
      photoreceptor spectral characteristics.
AB  - Microspectrophotometric examination of the retina of a procellariiform marine
      bird, the wedge-tailed shearwater Puffinus pacificus, revealed the presence of
      five different types of vitamin A(1)-based visual pigment in seven different
      types of photoreceptor. A single class of rod contained a medium-wavelength
      sensitive visual pigment with a wavelength of maximum absorbance (lambda(max)) at
      502 nm. Four different types of single cone contained visual pigments maximally
      sensitive in either the violet (VS, lambda(max) 406 nm), short (SWS, lambda(max)
      450 nm), medium (MWS, lambda(max) 503 nm) or long (LWS, lambda(max) 566 nm)
      spectral ranges. In the peripheral retina, the SWS, MWS and LWS single cones
      contained pigmented oil droplets in their inner segments with cut-off wavelengths
      (lambda(cut)) at 445 (C-type), 506 (Y-type) and 562 nm (R-type), respectively.
      The VS visual pigment was paired with a transparent (T-type) oil droplet that
      displayed no significant absorption above at least 370 nm. Both the principal and
      accessory members of the double cone pair contained the same 566 nm lambda(max)
      visual pigment as the LWS single cones but only the principal member contained an
      oil droplet, which had a lambda(cut) at 413 nm. The retina had a horizontal band
      or 'visual streak' of increased photoreceptor density running across the retina
      approximately 1.5 mm dorsal to the top of the pecten. Cones in the centre of the
      horizontal streak were smaller and had oil droplets that were either
      transparent/colourless or much less pigmented than at the periphery. It is
      proposed that the reduction in cone oil droplet pigmentation in retinal areas
      associated with high visual acuity is an adaptation to compensate for the reduced
      photon capture ability of the narrower photoreceptors found there. Measurements
      of the spectral transmittance of the ocular media reveal that wavelengths down to
      at least 300 nm would be transmitted to the retina.

PMID- 14978064
TI  - Magnetic orientation in the mealworm beetle Tenebrio and the effect of light.
AB  - There is evidence for both light-dependent and light-independent mechanisms of
      magnetoreception of terrestrial animals. One example of a light-independent
      mechanism frequently cited is the magnetic compass of the mealworm beetle
      (Tenebrio molitor). We found that magnetoreception of the mealworm beetle per se
      is a replicable phenomenon but that, in contrast to earlier findings, Tenebrio
      only exhibited consistent magnetic compass orientation when light was present.
      The problem of whether the loss of orientation is due to a light-dependent
      magnetoreception mechanism or is instead an effect of motivation change is
      discussed.

PMID- 14978065
TI  - The physiological consequences of exposure to chronic, sublethal waterborne
      nickel in rainbow trout (Oncorhynchus mykiss): exercise vs resting physiology.
AB  - In rainbow trout (Oncorhynchus mykiss), following chronic (42 day) exposure to
      both 384 microg Ni l(-1) and 2034 microg Ni l(-1), Ni accumulation was greatest
      in the gill, kidney and plasma, with the plasma as the main sink for Ni. Indeed,
      trapped plasma analysis revealed that extensive loading of Ni in the plasma
      accounted for substantial percentages of accumulated Ni in several tissues
      including the liver and heart. Accumulated Ni in the gill and kidney was less
      dependent on plasma Ni concentration, suggesting a more intracellular
      accumulation of Ni in these tissues. We present evidence for a clear, persistent
      cost of acclimation to chronic, sublethal Ni exposure. Chronic (40-99 day)
      exposure to sublethal waterborne Ni (243-394 microg Ni l(-1); approximately 1% of
      the 96 h LC(50)) impaired the exercise physiology, but not the resting
      physiology, of rainbow trout. Ni acted as a limiting stressor, decreasing maximal
      rates of oxygen consumption (MO2,max) during strenuous exercise in trout exposed
      for 34 days to sublethal Ni. This drop in high-performance gas exchange was
      attributed mainly to a reduction in relative branchial diffusing capacity
      (D(rel)) caused by thickening of secondary lamellae. Morphometric analysis of the
      gills of chronically exposed fish revealed overall swelling of secondary
      lamellae, as well as hypertrophic respiratory epithelia within secondary
      lamellae. Additionally, contraction of the lamellar blood pillar system and
      narrowing of interlamellar water channels occurred, possibly contributing to
      decreased high-performance gas exchange. Decreased aerobic capacity persisted in
      fish previously exposed to nickel despite a clean-water exposure period of 38
      days and an almost complete depuration of gill Ni, suggesting that extrabranchial
      mechanisms of chronic Ni toxicity may also be important. Chronic impairment of
      such a dynamically active and critical organ as the gill may depress the overall
      fitness of a fish by impairing predator avoidance, prey capture and migration
      success with obvious environmental implications.

PMID- 14978067
TI  - Dendritic cell activation kinetics and cancer immunotherapy.

PMID- 14978068
TI  - Lack of association between human switch recombination breakpoints and the
      secondary structure of targeted DNA regions.

PMID- 14978069
TI  - T cell-dependent and -independent responses.

PMID- 14978070
TI  - Of mice and not men: differences between mouse and human immunology.
AB  - Mice are the experimental tool of choice for the majority of immunologists and
      the study of their immune responses has yielded tremendous insight into the
      workings of the human immune system. However, as 65 million years of evolution
      might suggest, there are significant differences. Here we outline known
      discrepancies in both innate and adaptive immunity, including: balance of
      leukocyte subsets, defensins, Toll receptors, inducible NO synthase, the NK
      inhibitory receptor families Ly49 and KIR, FcR, Ig subsets, the B cell (BLNK,
      Btk, and lambda5) and T cell (ZAP70 and common gamma-chain) signaling pathway
      components, Thy-1, gammadelta T cells, cytokines and cytokine receptors, Th1/Th2
      differentiation, costimulatory molecule expression and function, Ag-presenting
      function of endothelial cells, and chemokine and chemokine receptor expression.
      We also provide examples, such as multiple sclerosis and delayed-type
      hypersensitivity, where complex multicomponent processes differ. Such differences
      should be taken into account when using mice as preclinical models of human
      disease.

PMID- 14978071
TI  - Cutting edge: activation of Toll-like receptor 2 induces a Th2 immune response
      and promotes experimental asthma.
AB  - Recognition of microbial components by APCs and their activation through Toll
      like receptors (TLR) leads to the induction of adaptive immune responses. In this
      study, we show that activation of TLR2 by its synthetic ligand Pam3Cys, in
      contrast to activation of TLR9 by immunostimulatory DNA (ISS-ODN), induces a
      prominent Th2-biased immune response. Activation of APCs by Pam3Cys resulted in
      the induction of Th2-associated effector molecules like IL-13, and IL-1beta, GM
      CSF and up-regulation of B7RP-1, but low levels of Th1-associated cytokines (IL
      12, IFNalpha, IL-18, IL-27). Accordingly, TLR2 ligands aggravated experimental
      asthma. These data indicate that the type of TLR stimulation during the initial
      phase of immune activation determines the polarization of the adaptive immune
      response and may play a role in the initiation of Th2-mediated immune disorders,
      such as asthma.

PMID- 14978072
TI  - Cutting edge: activity of human adult microglia in response to CC chemokine
      ligand 21.
AB  - The approximately 50 known chemokines are classified in distinct subfamilies:
      CXC, CC, CX3C, and C. Although the signaling of chemokines often is promiscuous,
      signaling events between members of these distinct chemokine classes are hardly
      observed. The only known exception so far is the murine CC chemokine ligand
      (CCL)21 (secondary lymphoid tissue chemokine, Exodus-2, 6Ckine), which binds and
      activates the murine CXC chemokine receptor CXCR3. However, this exception has
      not been found in humans. In this study, we provide evidence that human CCL21 is
      a functional ligand for endogenously expressed CXCR3 in human adult microglia. In
      absence of CCR7 expression, CCL21 induced chemotaxis of human microglia with
      efficiency similar to the CXCR3 ligands CXC chemokine ligand 9 (monokine induced
      by IFN-gamma) and CXC chemokine ligand 10 (IFN-gamma-inducible protein-10).
      Because human CCL21 did not show any effects in CXCR3-transfected HEK293 cells,
      it is indicated that CXCR3 signaling depends on the cellular background in which
      the CXCR3 is expressed.

PMID- 14978073
TI  - Cutting edge: a new approach to modeling early lung immunity in murine
      tuberculosis.
AB  - In this study, we report a new approach that allows dissection of distinct
      pathways regulating induction of early adaptive immunity in response to
      Mycobacterium tuberculosis (Mtb). We used traceable murine dendritic cells (DCs)
      and macrophage populations to chart their migratory pattern in response to Mtb,
      and found that only DCs receiving inflammatory stimuli from Mtb up-regulated
      their expression of CCR7 and migrated specifically to the draining lymph nodes
      (LNs). Furthermore, these Mtb-modulated DCs initiated a Th1 response only in the
      draining LNs. Taken together, these results demonstrate that Mtb-induced
      modulation of DCs is critical for their migration to regional LNs and ensuing T
      cell priming.

PMID- 14978074
TI  - Phosphatidylinositol 3-kinase-dependent mitogen-activated protein/extracellular
      signal-regulated kinase kinase 1/2 and NF-kappa B signaling pathways are required
      for B cell antigen receptor-mediated cyclin D2 induction in mature B cells.
AB  - Phosphatidylinositol 3-kinase (PI-3K) has been linked to promitogenic responses
      in splenic B cells following B cell Ag receptor (BCR) cross-linking; however
      identification of the signaling intermediates that link PI-3K activity to the
      cell cycle remains incomplete. We show that cyclin D2 induction is blocked by the
      PI-3K inhibitors wortmannin and LY294002, which coincides with impaired BCR
      mediated mitogen-activated protein/extracellular signal-related kinase kinase
      (MEK)1/2 and p42/44ERK phosphorylation on activation residues. Cyclin D2
      induction is virtually absent in B lymphocytes from mice deficient in the class
      I(A) PI-3K p85alpha regulatory subunit. In contrast to studies with PI-3K
      inhibitors, which inhibit all classes of PI-3Ks, the p85alpha regulatory subunit
      is not required for BCR-induced MEK1/2 and p42/44ERK phosphorylation, suggesting
      the contribution of another PI-3K family members in MEK1/2 and p42/44ERK
      activation. However, p85alpha(-/-) splenic B cells are defective in BCR-induced
      IkappaB kinase beta and IkappaBalpha phosphorylation. We demonstrate that NF
      kappaB signaling is required for cyclin D2 induction via the BCR in normal B
      cells, implicating a possible link with the defective IkappaB kinase beta and
      IkappaBalpha phosphorylation in p85alpha(-/-) splenic B cells and their ability
      to induce cyclin D2. These results indicate that MEK1/2-p42/44ERK and NF-kappaB
      pathways link PI-3K activity to Ag receptor-mediated cyclin D2 induction in
      splenic B cells.

PMID- 14978075
TI  - A role for IL-10-mediated HLA-DR7-restricted T cell-dependent events in
      development of the modified Th2 response to cat allergen.
AB  - Although high dose exposure to inhaled cat allergen (Fel d 1) can cause a form of
      tolerance (modified Th2 response), the T cell mechanism for this phenomenon has
      not been studied. T cell responses to Fel d 1 were characterized in both allergic
      (IgE(pos)) and modified Th2 (IgE(neg)IgG(pos)) responders as well as serum Ab
      negative controls (IgE(neg)IgG(neg)). Fel d 1 stimulated high levels of IL-10 in
      PBMC cultures from all individuals, with evidence of Th2 and Th1 cytokine skewing
      in allergic and control subjects, respectively. Using overlapping peptides,
      epitopes at the N terminus of Fel d 1 chain 2 were shown to stimulate strong T
      cell proliferation and to preferentially induce IL-10 (peptide 2:1 (P2:1)) or IFN
      gamma (P2:2) regardless of the allergic status of the donor. Injection of cat
      extract during conventional immunotherapy stimulated expansion of IL-10- and IFN
      gamma-producing chain 2 epitope-specific T cells along with increased Fel d 1
      specific serum IgG and IgG4 Ab. Six of 12 modified responders expressed the major
      HLA-DRB1 allele, *0701, and both P2:1 and P2:2 were predicted ligands for this
      allele. Cultures from DR7-positive modified responders produced the highest
      levels of IL-10 to P2:1 in addition to other major and minor epitopes within
      chains 1 and 2. In the presence of anti-IL-10 mAb, both T cell proliferation and
      IFN-gamma production were enhanced in a Fel d 1- and epitope-specific manner. We
      conclude that IL-10-producing T cells specific for chain 2 epitopes are relevant
      to tolerance induction, and that DR7-restricted recognition of these epitopes
      favors a modified Th2 response.

PMID- 14978076
TI  - Human thymus exports naive CD8 T cells that can home to nonlymphoid tissues.
AB  - Functionally naive CD8 T cells in peripheral blood from adult humans can be fully
      described by their CD45RA(bright)CCR7(+)CD62L(+) cell surface phenotype. Cord
      blood lymphocytes, from healthy newborns, are homogenously functionally naive.
      Accordingly, the majority of cord blood CD8 T cells express the same pattern of
      cell surface molecules. Unexpectedly, however, a significant fraction of cord
      blood CD8 T cells express neither CCR7 nor CD62L. Yet these cells remain
      functionally naive as they contain high levels of TCR excision circles, have long
      telomeres, display highly polyclonal TCRs, and do not exhibit immediate effector
      functions. In addition, these CD8 T cells already represent a significant
      fraction of the mature naive CD8 single-positive thymocyte repertoire and may
      selectively express the cutaneous lymphocyte Ag. We suggest that CD8 single
      positive thymocytes comprise two pools of naive precursors that exhibit distinct
      homing properties. Once seeded in the periphery, naive CCR7(+)CD62L(+) CD8 T
      cells patrol secondary lymphoid organs, whereas naive CCR7(-)CD62L(-) CD8 T cells
      selectively migrate to peripheral tissues such as skin.

PMID- 14978077
TI  - CD86 and CD80 differentially modulate the suppressive function of human
      regulatory T cells.
AB  - Regulatory T cells (Treg) are important in maintaining tolerance to self tissues.
      As both CD28 and CTLA-4 molecules are implicated in the function of Treg, we
      investigated the ability of their two natural ligands, CD80 and CD86, to
      influence the Treg-suppressive capacity. During T cell responses to alloantigens
      expressed on dendritic cells, we observed that Abs against CD86 potently enhanced
      suppression by CD4(+)CD25(+) Treg. In contrast, blocking CD80 enhanced
      proliferative responses by impairing Treg suppression. Intriguingly, the relative
      expression levels of CD80 and CD86 on dendritic cells are modulated during
      progression from an immature to a mature state, and this correlates with the
      ability of Treg to suppress responses. Our data show that CD80 and CD86 have
      opposing functions through CD28 and CTLA-4 on Treg, an observation that has
      significant implications for manipulation of immune responses and tolerance in
      vivo.

PMID- 14978078
TI  - The centromeric region of chromosome 7 from MRL mice (Lmb3) is an epistatic
      modifier of Fas for autoimmune disease expression.
AB  - Lupus is a prototypic systemic autoimmune disease that has a significant genetic
      component in its etiology. Several genome-wide screens have identified multiple
      loci that contribute to disease susceptibility in lupus-prone mice, including the
      Fas-deficient MRL/Fas(lpr) strain, with each locus contributing in a threshold
      liability manner. The centromeric region of chromosome 7 was identified as a
      lupus susceptibility locus in MRL/Fas(lpr) mice as Lmb3. This locus was
      backcrossed onto the resistant C57BL/6 (B6) background, in the presence or
      absence of Fas, resulting in the generation of B6.MRLc7 congenic animals.
      Detailed analysis of these animals showed that Lmb3 enhances and accelerates
      several characteristics of lupus, including autoantibody production, kidney
      disease, and T cell activation, as well as accumulation of CD4(-)CD8(-) double
      negative T cells, the latter a feature of Fas-deficient mice. These effects
      appeared to be dependent on the interaction between Lmb3 and Fas deficiency, as
      Lmb3 on the B6/+(Fas-lpr) background did not augment any of the lupus traits
      measured. These findings confirm the role of Lmb3 in lupus susceptibility, as a
      modifier of Fas(lpr) phenotype, and illustrate the importance of epistatic
      interaction between genetic loci in the etiology of lupus. Furthermore, they
      suggest that the genetic lesion(s) in MRLc7 is probably different from those in
      NZMc7 (Sle3/5), despite a significant overlap of these two intervals.

PMID- 14978079
TI  - The T cells specific for the carboxyl-terminal determinants of self (rat) heat
      shock protein 65 escape tolerance induction and are involved in regulation of
      autoimmune arthritis.
AB  - Immunization of Lewis rats with heat-killed Mycobacterium tuberculosis H37Ra
      leads to development of polyarthritis (adjuvant-induced arthritis; AA) that
      shares several features with human rheumatoid arthritis (RA). Immune response to
      the 65-kDa mycobacterial heat-shock protein (Bhsp65) is believed to be involved
      in induction of AA as well as in experimental modulation of this disease.
      However, the understanding of several critical aspects of the pathogenesis of AA
      in the Lewis rat has severely been hampered by the lack of information both
      regarding the level as well as epitope specificity of tolerance to the mammalian
      self (rat) homologue of Bhsp65, 65-kDa rat heat-shock protein (Rhsp65), and about
      the functional attributes of the T cell repertoire specific for this self
      protein. In this study, we established that tolerance to Rhsp65 in the Lewis rat
      is incomplete, and that the residual T cells primed upon challenge with this self
      hsp65 are disease regulating in nature. We also have defined the T cell epitopes
      in the C-terminal region within Rhsp65 that contribute predominantly to the
      immune reactivity as well as the AA-protective effect of this self protein.
      Furthermore, the T cells primed by peptides comprising these C-terminal
      determinants can be efficiently restimulated by the naturally generated epitopes
      from endogenous Rhsp65, suggesting that self hsp65 might also be involved in
      natural remission from acute AA. These novel first experimental insights into the
      self hsp65-directed regulatory T cell repertoire in AA would help develop better
      immunotherapeutic approaches for autoimmune arthritis.

PMID- 14978080
TI  - Transgenic expression of insulin receptor substrate 2 in murine B cells alters
      the cell density-dependence of IgE production in vitro and enhances IgE
      production in vivo.
AB  - Previous studies have shown that insulin receptor substrate (IRS)1 and IRS2
      mediate proliferative and antiapoptotic signaling through the IL-4R in 32D cells;
      however their role in regulating normal B cell responses is not clear. To
      investigate the role of IRS2 in normal B cell function, we developed IRS2
      transgenic (Tg) mice on the C57BL/6 background. Western blot analysis revealed a
      2-fold elevation in IRS2 protein levels in Tg(+) mice compared with littermate
      controls and a 3-fold increase in basal tyrosine phosphorylated IRS2 in the
      absence of IL-4 stimulation. IL-4-induced tyrosine phosphorylation of IRS2 was
      elevated in Tg(+) B cells, whereas IL-4-induced phosphorylation of STAT6 was
      similar between Tg(+) and Tg(-) B cells. Tg expression of IRS2 had little effect
      on IL-4-mediated proliferation and no effect on protection from apoptosis.
      However, production of IgE and IgG1 by Tg(+) B cells using standard in vitro
      conditions was diminished 50-60%. Because Ig production in vitro is known to be
      highly cell concentration-dependent, we performed experiments at different cell
      concentrations. Interestingly, at very low B cell concentrations (1000-5000 B
      cells/well), IgE and IgG1 production by Tg(+) B cells was greater than that of
      controls, whereas at higher cell concentrations (10,000-20,000 cells/well) Ig
      production by Tg(+) B cells was less than controls. Furthermore, in vivo
      immunization with OVA-alum or goat anti-IgD resulted in elevated serum IgE levels
      in the Tg(+) mice. These results indicate that overexpression of IRS2 alters the
      B cell intrinsic density-dependence of IgE and IgG1 production in vitro and
      enhances IgE responses in vivo.

PMID- 14978081
TI  - Circadian rhythms of granzyme B, perforin, IFN-gamma, and NK cell cytolytic
      activity in the spleen: effects of chronic ethanol.
AB  - Recent studies show that alterations in the body's biological rhythms can lead to
      serious pathologies, including cancer. Acute and chronic ethanol consumption
      impairs the immune system by causing specific defects in the cellular components
      of the innate immune response and by creating increased risk and susceptibility
      to infections and cancer. NK cells are critical for immune surveillance against
      infected and malignant cells. To assess whether NK cell function follows a
      circadian trend and to determine ethanol effects on this rhythm, we measured,
      over a 24-h period, mRNA and protein levels of granzyme B, perforin, and the
      cytokine IFN-gamma, as well as NK cell activity, in the splenocytes of ad libitum
      fed, pair-fed, and ethanol-fed Sprague Dawley male rats. Circadian rhythms were
      found in mRNA and protein levels of granzyme B, perforin, and IFN-gamma. A
      circadian pattern was also detected in NK cell cytolytic activity. Our data
      further demonstrated how chronic ethanol suppressed NK cell activity by directly
      disrupting the circadian rhythms of granzyme B, perforin, and IFN-gamma. These
      findings identify the circadian functions of splenic NK cells and show the
      vulnerability of these rhythms to chronic ethanol.

PMID- 14978082
TI  - IL-12 priming during in vitro antigenic stimulation changes properties of CD8 T
      cells and increases generation of effector and memory cells.
AB  - Antigenic and costimulatory signals trigger a developmental program by which
      naive CD8 T cells differentiate into effector and memory cells. However, initial
      cytokine signals that regulate the generation of effector and memory CD8 T cells
      are not well understood. In this study, we show that IL-12 priming during in
      vitro antigenic stimulation results in the significant increase of both primary
      and memory CD8 T cell population in mice after adoptive transfer of activated
      cells. The effect of IL-12 priming is closely associated with qualitative changes
      in CD8 T cells, such as reduced MHC I tetramer binding and CD69 expression,
      altered distribution of lipid rafts, decreased cytolytic activity, and less
      susceptibility to apoptosis. Furthermore, exogenous IL-12 priming improved the
      intrinsic survival properties of memory CD8 T cells, leading to better protective
      immunity and vaccine-induced memory CD8 T cell responses. However, the
      experiments with IL-12p40- and IL-12Rbeta1-deficient mice showed similar levels
      of primary and memory CD8 T cell responses compared with wild-type mice, implying
      that endogenous IL-12 and/or IL-12R signaling in vivo is not critical for CD8 T
      cell immunity. Together, our results suggest that IL-12 can serve as an
      important, but dispensable regulatory factor for the development of CD8 T cells,
      and IL-12 priming could be useful in many medical applications.

PMID- 14978083
TI  - Compromised humoral and delayed-type hypersensitivity responses in IL-23
      deficient mice.
AB  - The heterodimeric cytokine IL-23 consists of a private cytokine-like p19 subunit
      and a cytokine receptor-like subunit, p40, which is shared with IL-12. Previously
      reported IL-12p40-deficient mice have profound immune defects resulting from
      combined deficiency in both IL-12 and IL-23. To address the effects of specific
      IL-23 deficiency, we generated mice lacking p19 by gene targeting. These mice
      display no overt abnormalities but mount severely compromised T-dependent humoral
      immune responses. IL-23p19(-/-) mice produce strongly reduced levels of Ag
      specific Igs of all isotypes, but mount normal T-independent B cell responses. In
      addition, delayed type hypersensitivity responses are strongly impaired in the
      absence of IL-23, indicating a defect at the level of memory T cells. T cells
      stimulated with IL-23-deficient APCs secrete significantly reduced amounts of the
      proinflammatory cytokine IL-17, and IL-23-deficient mice phenotypically resemble
      IL-17-deficient animals. Thus, IL-23 plays a critical role in T cell-dependent
      immune responses, and our data provide further support for the existence of an IL
      23/IL-17 axis of communication between the adaptive and innate parts of the
      immune system.

PMID- 14978084
TI  - CD4 T cell-dependent CD8 T cell maturation.
AB  - We have investigated the contribution of CD4 T cells to the optimal priming of
      functionally robust memory CD8 T cell subsets. Intranasal infection of CD4 T cell
      deficient (CD4(-/-)) mice with lymphocytic choriomeningitis virus resulted in the
      elaboration of virus-specific CD8 T cell responses that cleared the infection.
      However, by comparison with normal mice, the virus-specific CD8 T cells in CD4(-/
      ) mice were quantitatively and qualitatively different. In normal mice,
      lymphocytic choriomeningitis virus-specific memory CD8 T cells are CD44(high),
      many are CD122(high), and a majority of these cells regain expression of CD62L
      overtime. These cells produce IFN-gamma and TNF-alpha, and a subset also produces
      IL-2. In the absence of CD4 T cell help, a distinct subset of memory CD8 T cells
      develops that remains CD62L(low) up to 1 year after infection and exhibits a
      CD44(int)CD122(low) phenotype. These cells are qualitatively different from their
      counterparts in normal hosts, as their capacity to produce TNF-alpha and IL-2 is
      diminished. In addition, although CD4-independent CD8 T cells can contain the
      infection following secondary viral challenge, their ability to expand is
      impaired. These findings suggest that CD4 T cell responses not only contribute to
      the optimal priming of CD8 T cells in chronically infected hosts, but are also
      critical for the phenotypic and functional maturation of CD8 T cell responses to
      Ags that are more rapidly cleared. Moreover, these data imply that the
      development of CD62L(high) central memory CD8 T cells is arrested in the absence
      of CD4 T cell help.

PMID- 14978085
TI  - Mannose receptor targeting of tumor antigen pmel17 to human dendritic cells
      directs anti-melanoma T cell responses via multiple HLA molecules.
AB  - Targeting recycling endocytic receptors with specific Abs provides a means for
      introducing a variety of tumor-associated Ags into human dendritic cells (DCs),
      culminating in their efficient presentation to T cells. We have generated a human
      mAb (B11) against the mannose receptor that is rapidly internalized by DCs
      through receptor-mediated endocytosis. By genetically linking the melanoma Ag,
      pmel17, to Ab B11, we obtained the fully human fusion protein, B11-pmel17.
      Treatment of DCs with B11-pmel17 resulted in the presentation of pmel17 in the
      context of HLA class I and class II molecules. Thus, potent pmel17-specific T
      cells were cytotoxic toward gp100(+) HLA-matched melanoma targets, but not HLA
      mismatched melanoma or gp100(-) nonmelanoma tumor lines. Importantly, competitive
      inhibition of lysis of an otherwise susceptible melanoma cell line by cold
      targets pulsed with known gp100 CD8 T cell epitopes as well as a dose-dependent
      proliferative response to Th epitopes demonstrates that DCs can process targeted
      Ag for activation of cytotoxic as well as helper arms of the immune response.
      Thus, the specific targeting of soluble exogenous tumor Ag to the DC mannose
      receptor directly contributes to the generation of multiple HLA-restricted Ag
      specific T cell responses.

PMID- 14978086
TI  - Depletion of CXCR2 inhibits tumor growth and angiogenesis in a murine model of
      lung cancer.
AB  - The Glu-Leu-Arg(+) (ELR(+)) CXC chemokines are potent promoters of angiogenesis
      and have been demonstrated to induce a significant portion of nonsmall cell lung
      cancer-derived angiogenic activity and support tumorigenesis. ELR(+) CXC
      chemokines share a common chemokine receptor, CXCR2. We hypothesized that CXCR2
      mediates the proangiogenic effects of ELR(+) CXC chemokines during tumorigenesis.
      To test this postulate, we used syngeneic murine Lewis lung cancer (LLC; 3LL, H
      2(b)) heterotopic and orthotopic tumor model systems in C57BL/6 mice replete
      (CXCR2(+/+)) and deficient in CXCR2 (CXCR2(-/-)). We first demonstrated a
      correlation of the expression of endogenous ELR(+) CXC chemokines with tumor
      growth and metastatic potential of LLC tumors. Next, we found that LLC primary
      tumors were significantly reduced in growth in CXCR2(-/-) mice. Moreover, we
      found a marked reduction in the spontaneous metastases of heterotopic tumors to
      the lungs of CXCR2(-/-) mice. Morphometric analysis of the primary tumors in
      CXCR2(-/-) mice demonstrated increased necrosis and reduced vascular density.
      These findings were further confirmed in CXCR2(+/+) mice using specific
      neutralizing Abs to CXCR2. The results of these studies support the notion that
      CXCR2 mediates the angiogenic activity of ELR(+) CXC chemokines in a preclinical
      model of lung cancer.

PMID- 14978087
TI  - Lassa virus infection of human dendritic cells and macrophages is productive but
      fails to activate cells.
AB  - Lassa fever is a hemorrhagic fever caused by Lassa virus (LV), an old-world
      Arenavirus. Little is known about the immune responses that occur during the
      disease, but protection seems to be linked to the induction of cellular responses
      specific for viral glycoproteins. Conversely, severe Lassa fever may be
      associated with immunosuppression. We studied the infection of human dendritic
      cells (DC) and macrophages (MP) by LV. Both these cell types are susceptible to
      LV infection. Viral nucleoprotein was detected in DC and MP, and high and
      moderate viral titers were obtained with culture supernatants of DC and MP,
      respectively. LV did not induce apoptosis in DC and MP. These cells were not
      activated by LV infection. No change was observed in the expression of surface
      molecules involved in activation, costimulation, adhesion, and Ag presentation
      following LV infection, or in the functional properties of DC. Inflammatory
      cytokine production was not detected at the mRNA or protein level after LV
      infection of DC and MP. Thus, MP, and particularly DC, are crucial targets for LV
      and are probably involved in the early replication of LV from the initial site of
      infection. The lack of activation and maturation of cells following infection may
      be associated with the immunosuppression observed in severe LV infection.

PMID- 14978088
TI  - In vivo VL-targeted activation-induced apoptotic supraclonal deletion by a
      microbial B cell toxin.
AB  - To interfere with host immune responses, some microbial pathogens produce
      proteins with the properties of superantigens, which can interact via conserved V
      region framework subdomains of the Ag receptors of lymphocytes rather than the
      complementarity-determining region involved in the binding of conventional Ags.
      In recent studies, we have elucidated how a model B cell superantigen affects the
      host immune system by targeting a conserved V(H) site on the Ag receptors of B
      lymphocytes. To determine whether these findings represent a general paradigm, we
      investigated the in vivo immunobiologic properties of protein L of
      Peptostreptococcus magnus (PpL), a microbial Ig-binding protein specific for a V
      region site on Ig L chains. Our studies confirmed that PpL binding is restricted
      to a subset of murine Vkappa-expressing B cells, and found that B cells with
      stronger PpL-binding activity are associated with certain B cell subsets: splenic
      marginal zone (CD21(high) CD23(low)), splenic CD1(+), peritoneal B-1a (IgD(low)
      CD5(+)), and CD21(high) CD24(high) B cells in peripheral lymph nodes, mesenteric
      lymph nodes, and Peyer's patches. Infusion of PpL triggered a sequence of events
      in B cell receptor (BCR)-targeted B cells, with rapid down-regulation of BCR, the
      induction of an activation phenotype, and limited rounds of proliferation.
      Apoptosis followed through a process heralded by the dissipation of mitochondrial
      membrane potential, the induction of the caspase pathway, DNA fragmentation, and
      the deposition of B cell apoptotic bodies. These studies define a common pathway
      by which microbial toxins that target V region-associated BCR sites induce
      programmed cell death.

PMID- 14978089
TI  - Analysis of autoreactive CD4 T cells in experimental autoimmune encephalomyelitis
      after primary and secondary challenge using MHC class II tetramers.
AB  - Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple
      sclerosis, is primarily mediated by CD4 T cells specific for Ags in the CNS.
      Using MHC class II tetramers, we assessed expansion and phenotypic
      differentiation of polyclonal self-reactive CD4 T cells during EAE after primary
      and secondary challenge with the specific Ag. After EAE induction in SJL mice
      with proteolipid protein 139-151, CNS-specific T cells up-regulated activation
      markers and expanded in the draining lymph nodes and in the spleen. Less than 20%
      of total autoreactive T cells entered the CNS simultaneously with Th cells of
      other specificities. Almost all tetramer-positive cells in the CNS were activated
      and phenotypically distinct from the large peripheral pool. When EAE was induced
      in Ag-experienced mice, disease symptoms developed earlier and persisted longer;
      autoreactive T cells were more rapidly activated and invaded the CNS earlier. In
      striking contrast to specific CTLs that respond after secondary viral challenge,
      the absolute numbers of autoreactive CD4 T cells were not increased, indicating
      that the accelerated autoreactivity in Ag-experienced mice is not related to
      higher frequencies of autoreactive CD4 T cells.

PMID- 14978090
TI  - A role for Toll-like receptor 4 in dendritic cell activation and cytolytic CD8+ T
      cell differentiation in response to a recombinant heat shock fusion protein.
AB  - Recombinant heat shock fusion proteins (Hsfp) injected into mice without added
      adjuvants can stimulate production of CD8 cytolytic T cells. Because initiation
      of productive immune responses generally requires dendritic cell (DC) activation,
      the question arises as to whether the Hsfp can activate DC independently of
      contaminating LPS. Using microarray analyses of DC from LPS-insensitive mice
      having a point mutation in Toll-like receptor 4 (Tlr4) (C3H/HeJ), or lacking Tlr4
      (B10/ScNCr), we show here that unlike a LPS standard, Hsfp activated DC from HeJ
      mice almost as well as DC from wild-type mice. Consistent with the microarray
      analysis, the Hsfp's ability to activate DC was not eliminated by polymyxin B but
      was destroyed by proteinase K. The Hsfp did not, however, stimulate DC from mice
      lacking Tlr4. In vivo the CD8 T cell response to the Hsfp in mice lacking Tlr4
      was impaired: the responding CD8 cells initially proliferated vigorously but
      their development into cytolytic effector cells was diminished. Overall, the
      results indicate that this Hsfp can activate DC independently of LPS but still
      requires Tlr4 for an optimal CD8 T cell response.

PMID- 14978091
TI  - Different potentials of gamma delta T cell subsets in regulating airway
      responsiveness: V gamma 1+ cells, but not V gamma 4+ cells, promote airway
      hyperreactivity, Th2 cytokines, and airway inflammation.
AB  - Allergic airway inflammation and hyperreactivity are modulated by gammadelta T
      cells, but different experimental parameters can influence the effects observed.
      For example, in sensitized C57BL/6 and BALB/c mice, transient depletion of all
      TCR-delta(+) cells just before airway challenge resulted in airway
      hyperresponsiveness (AHR), but caused hyporesponsiveness when initiated before
      i.p. sensitization. Vgamma4(+) gammadelta T cells strongly suppressed AHR; their
      depletion relieved suppression when initiated before challenge, but not before
      sensitization, and they suppressed AHR when transferred before challenge into
      sensitized TCR-Vgamma4(-/-)/6(-/-) mice. In contrast, Vgamma1(+) gammadelta T
      cells enhanced AHR and airway inflammation. In normal mice (C57BL/6 and BALB/c),
      enhancement of AHR was abrogated only when these cells were depleted before
      sensitization, but not before challenge, and with regard to airway inflammation,
      this effect was limited to C57BL/6 mice. However, Vgamma1(+) gammadelta T cells
      enhanced AHR when transferred before challenge into sensitized B6.TCR-delta(-/-)
      mice. In this study Vgamma1(+) cells also increased levels of Th2 cytokines in
      the airways and, to a lesser extent, lung eosinophil numbers. Thus, Vgamma4(+)
      cells suppress AHR, and Vgamma1(+) cells enhance AHR and airway inflammation
      under defined experimental conditions. These findings show how gammadelta T cells
      can be both inhibitors and enhancers of AHR and airway inflammation, and they
      provide further support for the hypothesis that TCR expression and function
      cosegregate in gammadelta T cells.

PMID- 14978092
TI  - A novel anti-inflammatory role of simvastatin in a murine model of allergic
      asthma.
AB  - Statins, the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, are effective
      serum cholesterol-lowering agents in clinical practice, and they may also have
      anti-inflammatory properties. Asthma is characterized by chronic eosinophilic
      inflammation in the airways, which is thought to be regulated by the activity of
      T lymphocytes. We therefore examined the anti-inflammatory activity of
      simvastatin in a murine model of allergic asthma. In mice previously sensitized
      to OVA, simvastatin treatment, either orally or i.p., reduced the total
      inflammatory cell infiltrate and eosinophilia in bronchoalveolar lavage fluid in
      response to inhaled OVA challenge. Simvastatin therapy i.p. was also associated
      with a reduction in IL-4 and IL-5 levels in bronchoalveolar lavage fluid and, at
      higher doses, a histological reduction in inflammatory infiltrates in the lungs.
      OVA-induced IL-4, IL-5, IL-6, and IFN-gamma secretion was reduced in thoracic
      lymph node cultures from simvastatin-treated mice. Simvastatin treatment did not
      alter serum total IgE or OVA-specific IgG1 and IgG2a levels. These data
      demonstrate the therapeutic potential of statin-sensitive pathways in allergic
      airways disease.

PMID- 14978093
TI  - IL-12 inhibits thymic involution by enhancing IL-7- and IL-2-induced thymocyte
      proliferation.
AB  - IL-12 has been reported to affect thymic T cell selection, but the role of IL-12
      in thymic involution has not been studied. We found that in vivo, IL-12b knockout
      (IL-12b(-/-)) mice exhibited accelerated thymic involution compared with wild
      type (WT) B6 mice. This is characterized by an increase in thymocytes with the
      early development stage phenotype of CD25(-)CD44(+)CD4(-)CD8(-) in aged IL-12b(-/
      ) mice. Histologically, there were accelerated degeneration of thymic
      extracellular matrix and blood vessels, a significantly decreased thymic
      cortex/medulla ratio, and increased apoptotic cells in aged IL-12b(-/-) mice
      compared with WT mice. There was, however, no apparent defect in thymic structure
      and thymocyte development in young IL-12(-/-) mice. These results suggest the
      importance of IL-12 in maintaining thymic integrity and function during the aging
      process. Surprisingly, in WT B6 mice, there was no age-related decrease in the
      levels of IL-12 produced from thymic dendritic cells. Stimulation of thymocytes
      with IL-12 alone also did not enhance the thymocyte proliferative response in
      vitro. IL-12, however, provided a strong synergistic effect to augment the IL-7
      or IL-2 induced thymocyte proliferative response, especially in aged WT and IL
      12b(-/-) mice. Our data strongly support the role of IL-12 as an enhancement
      cytokine, which acts through its interactions with other cytokines to maintain
      thymic T cell function and development during aging.

PMID- 14978094
TI  - Spontaneous organ-specific Th2-mediated autoimmunity in TCR transgenic mice.
AB  - CD4(+) T cells that lead to autoimmune gastritis (AIG) in BALB/c mice are either
      Th1 or Th2 cells. To test whether the phenotype of disease is related to the
      particular TCR expressed by the pathogenic cell, we have generated several lines
      of TCR transgenic mice using receptors cloned from pathogenic Th1 or Th2 cells.
      We previously described spontaneous inflammatory AIG in A23 mice, caused by the
      transgenic expression of the TCR from a Th1 clone, TXA23. In this study we
      describe the generation of A51 mouse lines, transgenic for the TCR of a CD4(+)
      self-reactive Th2 clone, TXA51. A proportion of A51 mice spontaneously develop
      AIG by 10 wk of age, with a disease characterized by eosinophilic infiltration of
      the gastric mucosa and Th2 differentiation of transgenic T cells in the gastric
      lymph node. The Th2 phenotype of this autoimmune response seems to be related to
      a low availability of MHC class II-self peptide complexes. This in vivo model of
      spontaneous Th2-mediated, organ-specific autoimmunity provides a unique example
      in which the clonotypic TCR conveys the Th2 disease phenotype.

PMID- 14978095
TI  - Differential segmental flexibility and reach dictate the antigen binding mode of
      chimeric IgD and IgM: implications for the function of the B cell receptor.
AB  - Mature, naive B cells coexpress IgD and IgM with identical binding sites. In this
      study, the binding properties of such IgM and IgD are compared to determine how
      size and shape may influence their ability to bind Ag and thus function as
      receptors. To dissect their intrinsic binding properties, recombinant IgM and IgD
      were produced in soluble form as monomers of the basic H(2)L(2) Ab architecture,
      each with two Ag binding sites. Since these sites are connected with a hinge
      region in IgD and structural Ig domains in IgM, the two molecules differ
      significantly in this region. The results show that IgD exhibited the larger
      angle and longer distance between its binding sites, as well as having the
      greater flexibility. Relative functional affinity was assessed on two antigenic
      surfaces with high or low epitope density, respectively. At high epitope density,
      IgM had a higher functional affinity for the Ag compared with IgD. The order was
      reversed at low epitope density due to a decrease in the functional affinity of
      IgM. Studies of binding kinetics showed similar association rates for both
      molecules. The dissociation rate, however, was slower for IgM at high epitope
      density and for IgD at low epitope density. Taken together, the results show that
      IgM and IgD with identical Ag binding regions have different Ag binding
      properties.

PMID- 14978096
TI  - Posttranscriptional inhibition of gene expression by Mycobacterium tuberculosis
      offsets transcriptional synergism with IFN-gamma and posttranscriptional up
      regulation by IFN-gamma.
AB  - Host defense against Mycobacterium tuberculosis requires the cytokine IFN-gamma
      and IFN regulatory factor 1 (IRF-1), a transcription factor that is induced to
      high levels by IFN-gamma. Therefore, we chose to study regulation of IRF-1
      expression as a model for effects of M. tuberculosis on response to IFN-gamma. We
      found that IRF-1 mRNA abundance increased far more than transcription rate in
      human monocytic THP-1 cells stimulated by IFN-gamma, but less than transcription
      rate in cells infected by M. tuberculosis. IFN-gamma stimulation of infected
      cells caused a synergistic increase in IRF-1 transcription, yet IRF-1 mRNA
      abundance was similar in uninfected and infected cells stimulated by IFN-gamma,
      as was the IRF-1 protein level. Comparable infection by Mycobacterium bovis
      bacillus Calmette-Guerin failed to induce IRF-1 expression and had no effect on
      the response to IFN-gamma. We also examined the kinetics of transcription, the
      mRNA t(1/2), and the distribution of IRF-1 transcripts among total nuclear RNA,
      poly(A) nuclear RNA, and poly(A) cytoplasmic RNA pools in cells that were
      infected by M. tuberculosis and/or stimulated by IFN-gamma. Our data suggest that
      infection by M. tuberculosis inhibits RNA export from the nucleus. Moreover, the
      results indicate that regulated entry of nascent transcripts into the pool of
      total nuclear RNA affects IRF-1 expression and that this process is stimulated by
      IFN-gamma and inhibited by M. tuberculosis. The ability of infection by M.
      tuberculosis to limit the increase in IRF-1 mRNA expression that typically
      follows transcriptional synergism may contribute to the pathogenicity of M.
      tuberculosis.

PMID- 14978097
TI  - Toward a definition of self: proteomic evaluation of the class I peptide
      repertoire.
AB  - MHC class I molecules present host- and pathogen-derived peptides for immune
      surveillance. Much attention is given to the search for viral and tumor nonself
      peptide epitopes, yet the question remains, "What is self?" Analyses of Edman
      motifs and of small sets of individual peptides suggest that the class I self
      repertoire consists of thousands of different peptides. However, there exists no
      systematic characterization of this self-peptide backdrop, causing the definition
      of class I-presented self to remain largely hypothetical. To better understand
      the breadth and nature of self proteins sampled by class I HLA, we sequenced >200
      endogenously loaded HLA-B*1801 peptides from a human B cell line. Peptide-source
      proteins, ranging from actin-related protein 6 to zinc finger protein 147,
      possessed an assortment of biological and molecular functions. Major categories
      included binding proteins, catalytic proteins, and proteins involved in cell
      metabolism, growth, and maintenance. Genetically, peptides encoded by all
      chromosomes were presented. Statistical comparison of proteins presented by class
      I vs the human proteome provides empiric evidence that the range of proteins
      sampled by class I is relatively unbiased, with the exception of RNA-binding
      proteins that are over-represented in the class I peptide repertoire. These data
      show that, in this cell line, class I-presented self peptides represent a
      comprehensive and balanced summary of the proteomic content of the cell.
      Importantly, virus- and tumor-induced changes in virtually any cellular
      compartment or to any chromosome can be expected to be presented by class I
      molecules for immune recognition.

PMID- 14978098
TI  - A regulatory role for CD37 in T cell proliferation.
AB  - CD37 is a leukocyte-specific protein belonging to the tetraspanin superfamily.
      Previously thought to be predominantly a B cell molecule, CD37 is shown in this
      study to regulate T cell proliferation. CD37-deficient (CD37(-/-)) T cells were
      notably hyperproliferative in MLR, in response to Con A, or CD3-TCR engagement
      particularly in the absence of CD28 costimulation. Hyperproliferation was not due
      to differences in memory to naive T cell ratios in CD37(-/-) mice, apoptosis, or
      TCR down-modulation. Division cycle analyses revealed CD37(-/-) T cells to enter
      first division earlier than wild-type T cells. Importantly, proliferation of
      CD37(-/-) T cells was preceded by enhanced early IL-2 production. We hypothesized
      CD37 to be involved in TCR signaling and this was supported by the observation
      that CD4/CD8-associated p56(Lck) kinase activity was increased in CD37(-/-) T
      cells. Remarkably, CD37 cross-linking on human T cells transduced signals that
      led to complete inhibition of CD3-induced proliferation. In the presence of CD28
      costimulation, CD37 engagement still significantly reduced proliferation. Taken
      together, these results demonstrate a regulatory role for CD37 in T cell
      proliferation by influencing early events of TCR signaling.

PMID- 14978099
TI  - All known in vivo functions of the Oct-2 transcription factor require the C
      terminal protein domain.
AB  - Oct-2, a transcription factor expressed in the B lymphocyte lineage and in the
      developing CNS, functions through of a number of discrete protein domains. These
      include a DNA-binding POU homeodomain flanked by two transcriptional activation
      domains. In vitro studies have shown that the C-terminal activation domain, a
      serine-, threonine- and proline-rich sequence, possesses unique qualities,
      including the ability to activate transcription from a distance in a B cell
      specific manner. In this study, we describe mice in which the endogenous oct-2
      gene has been modified through gene targeting to create a mutated allele, oct
      2DeltaC, which encodes Oct-2 protein isoforms that lack all sequence C-terminal
      to the DNA-binding domain. Surprisingly, despite the retention of the DNA-binding
      domain and the glutamine-rich N-terminal activation domain, the truncated
      protein(s) encoded by the oct-2DeltaC allele are unable to rescue any of the
      previously described defects exhibited by oct-2 null mice. Homozygous oct
      2DeltaC/DeltaC mice die shortly after birth, and B cell maturation, B-1 cell self
      renewal, serum Ig levels, and B lymphocyte responses to in vitro stimulation are
      all reduced or absent, to a degree equivalent to that seen in oct-2 null mice. We
      conclude that the C-terminal activation domain of Oct-2 is required to mediate
      the unique and indispensable functions of the Oct-2 transcription factor in vivo.

PMID- 14978100
TI  - Relevance of posttranslational modifications for the arthritogenicity of type II
      collagen.
AB  - To establish the role of posttranslational modification in modulating the immune
      response to collagen, recombinant human type II collagen (rCII) was produced
      using a yeast expression system (rCII(pic)) and a baculovirus expression system
      (rCII(bac)). The biosynthesis of CII requires extensive posttranslational
      modification including the hydroxylation of prolyl and lysyl residues and
      glycosylation of selected hydroxylysyl residues. Amino acid analyses indicated
      that the rCII(bac) was adequately hydroxylated at prolyl residues but
      underhydroxylated at lysyl residues and underglycosylated compared with tissue
      derived CII, whereas rCII(pic) was adequately hydroxylated at prolyl residues but
      unhydroxylated at lysyl residues and had no glycosylation. When DBA/1 mice were
      immunized with rCII, rCII(pic) induced a lower incidence of arthritis than tissue
      derived CII, whereas rCII(bac) induced an intermediate level of arthritis. The
      severity of the arthritis was significantly lower in mice immunized with
      rCII(pic) compared with mice immunized with tissue-derived CII, whereas that of
      rCII(bac) was intermediate. These data indicate that the degree of lysine
      hydroxylation and glycosylation plays a role in the induction of arthritis. The
      recombinant collagens were then compared with tissue-derived CII when given as
      i.v. or oral tolerogens to suppress arthritis. Both recombinant collagens were
      less potent than tissue-derived CII, and this decrease in arthritis was
      associated with a decrease in Ab response to CII. These data suggest that the
      degree of glysosylation affects the immune response to CII, so that
      underglycosylated CII is less effective in the induction of arthritis and in its
      ability to suppress collagen-induced arthritis.

PMID- 14978101
TI  - The Ig-like domain of tapasin influences intermolecular interactions.
AB  - Presentation of antigenic peptides to T lymphocytes by MHC class I molecules is
      regulated by events involving multiple endoplasmic reticulum proteins, including
      tapasin. By studying the effects of substitutions in the tapasin Ig-like domain,
      we demonstrated that H-2L(d)/tapasin association can be segregated from
      reconstitution of folded L(d) surface expression. This finding suggests that
      peptide acquisition by L(d) is influenced by tapasin functions that are
      independent of L(d) binding. We also found that the presence of a nine-amino acid
      region in the Ig-like domain of mouse or human tapasin is required for
      association with L(d), and certain point substitutions in this sequence abrogate
      human, but not mouse, tapasin association with L(d). These data are consistent
      with a higher overall affinity between L(d) and mouse tapasin compared with human
      tapasin. In addition, we found that other point mutations in the same region of
      the tapasin Ig-like domain affect MHC class I surface expression and Ag
      presentation. Finally, we showed that the cysteine residues in the Ig-like domain
      of tapasin influence tapasin's stability, its interaction with the MHC class I H
      chain, and its stabilization of TAP. Mutagenesis of these cysteines decreases
      tapasin's electrophoretic mobility, suggesting that these residues form an
      intramolecular disulfide bond. Taken together, these results reveal a critical
      role for the tapasin Ig-like domain in tapasin function.

PMID- 14978102
TI  - Physical and functional interactions between Daxx and DNA methyltransferase 1
      associated protein, DMAP1.
AB  - Daxx has been shown to play an essential role in type I IFN-alphabeta-mediated
      suppression of B cell development and apoptosis. Recently, we demonstrated that
      Tyk2 is directly involved in IFN signaling for the induction and translocation of
      Daxx, which may result in growth arrest and/or apoptosis of B lymphocyte
      progenitors. To clarify how Daxx regulates B cell development, we examined Daxx
      interacting partners by yeast two-hybrid screening. DNA methyltransferase 1
      (DNMT1)-associated protein (DMAP1) was identified and demonstrated to interact
      with Daxx. The interaction regions in both proteins were mapped, and the cellular
      localization of the interaction was examined. Both Daxx and DMAP1 formed a
      complex with DNMT1 and colocalized in the nucleus. DMAP1 enhanced Daxx-mediated
      repression of glucocorticoid receptor transcriptional activity. Furthermore, Daxx
      protected protein degradation of DMAP1 in vivo. These results provide the novel
      molecular link between Daxx and DNMT1, which establishes a repressive
      transcription complex in the nucleus.

PMID- 14978103
TI  - A peptide that antagonizes TCR-mediated reactions with both syngeneic and
      allogeneic agonists: functional and structural aspects.
AB  - We identify and consider some characteristics of a peptide antagonist for the Ag
      specific receptor on 2C cells (the 2C TCR). The peptide, GNYSFYAL (called GNY),
      binds to H-2K(b), and a very high-resolution crystal structure of the GNY-K(b)
      complex at 1.35 A is described. Although the GNY peptide does not bind to L(d),
      the potency of GNY-K(b) as an antagonist is evident from its ability to
      specifically inhibit 2C TCR-mediated reactions to an allogenic agonist complex
      (QLSPFPFDL-L(d)), as well as to a syngeneic agonist complex (SIYRYYGL-K(b)). The
      crystal structure and the activities of alanine-substituted peptide variants
      point to the properties of the peptide P4 side chain and the conformation of the
      Tyr-P6 side chain as the structural determinants of GNYSFYAL antagonist activity.

PMID- 14978104
TI  - Toxoplasma gondii interferes with lipopolysaccharide-induced mitogen-activated
      protein kinase activation by mechanisms distinct from endotoxin tolerance.
AB  - We show in this study that Toxoplasma gondii infection induces rapid activation
      of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated
      kinase 1/2, and stress-activated protein kinase/c-Jun N-terminal kinase MAPK,
      followed promptly by their deactivation in mouse macrophages. Nevertheless, when
      infected cells were subsequently subjected to LPS triggering, MAPK activation was
      severely defective, in particular in the case of p38 MAPK, which is required for
      LPS-triggered TNF-alpha and IL-12 production. Similar effects occurred during
      endotoxin tolerance, but the phenomena were distinct. LPS pretriggering failed to
      activate the major p38 MAPK kinase, MAPK kinase 3/6. Toxoplasma infection, in
      contrast, resulted in sustained activation of this kinase. Furthermore, endotoxin
      pre-exposure blocked IkappaBalpha degradation upon subsequent LPS triggering, but
      this was not the case for Toxoplasma preinfection. Endotoxin-mediated down
      regulation of the LPS receptor, Toll-like receptor 4, has been suggested as one
      possible mechanism contributing to tolerance, and we found in this study that LPS
      down-modulated Toll-like receptor 4 expression. In contrast, Toxoplasma infection
      induced up-regulation of this pattern recognition receptor. Our results show that
      T. gondii blocks LPS-triggered cytokine production in part through MAPK
      inactivation, and that this occurs through pathways distinct from endotoxin
      induced tolerance.

PMID- 14978105
TI  - A type I IFN-dependent pathway induced by Schistosoma mansoni eggs in mouse
      myeloid dendritic cells generates an inflammatory signature.
AB  - Schistosomes are helminth parasites that display a dual impact on the immune
      system of their hosts. Although the larval stage, also known as schistosomulum,
      appears to subvert the host defenses, the egg stage induces strong inflammatory
      reactions. Given the pivotal role of dendritic cells (DC) in initiating and
      regulating immune responses, we compared the distinct transcriptional programs
      induced in immature mouse DC by S. mansoni eggs or schistosomula. Although SLA
      abrogated the transcription of many genes implicated in DC functions, eggs caused
      myeloid DC to produce IFN-beta. Autocrine/paracrine signaling through the type I
      IFN receptor in response to eggs was necessary for the induction of known IFN
      responsive genes and enhanced the synthesis of key inflammatory products. Taken
      as a whole, our data provide molecular insights into the immune evasion mechanism
      of schistosomula and suggest an unexpected role for type I IFN in the innate
      response to helminth eggs.

PMID- 14978106
TI  - Essential involvement of IFN-gamma in Clostridium difficile toxin A-induced
      enteritis.
AB  - Clostridium difficile has emerged as the important causative agent of antibiotics
      associated pseudomembranous colitis; especially its toxin A is presumed to be
      responsible for the colitis. We examined the pathophysiological roles of IFN
      gamma in toxin A-induced enteritis using IFN-gamma knockout (KO) mice. When toxin
      A of C. difficile was injected into the ileal loops of BALB/c wild-type (WT)
      mice, massive fluid secretion, disruption of intestinal epithelial structure, and
      massive neutrophil infiltration developed within 4 h after the injection. IFN
      gamma protein was faintly detected in some CD3-positive lymphocytes in the lamina
      propria and submucosa of the ileum of untreated WT mice. On the contrary, at 2
      and 4 h after toxin A injection, IFN-gamma protein was detected in infiltrating
      neutrophils and to a lesser degree in CD3-positive lymphocytes. In the ileum of
      WT mice, toxin A treatment markedly enhanced the gene expression of TNF-alpha,
      macrophage inflammatory protein-1alpha and -2, KC, and ICAM-1 >2 h after
      treatment. In contrast, the histopathological changes were marginal, without
      enhanced fluid secretion in the ileum of toxin A-treated IFN-gamma KO mice.
      Moreover, toxin A-induced gene expression of TNF-alpha, neutrophil chemotactic
      chemokines, and ICMA-1 was remarkably attenuated in IFN-gamma KO mice.
      Furthermore, pretreatment of WT mice with a neutralizing anti-IFN-gamma Ab
      prevented toxin A-induced enteritis. These observations indicate that IFN-gamma
      is the crucial mediator of toxin A-induced acute enteritis and suggest that IFN
      gamma is an important molecular target for the control of C. difficile-associated
      pseudomembranous colitis.

PMID- 14978107
TI  - Targeting of secretory IgA to Peyer's patch dendritic and T cells after transport
      by intestinal M cells.
AB  - In addition to being instrumental to the protection of mucosal epithelia,
      secretory IgA (SIgA) adheres to and is transported by intestinal Peyer's patch
      (PP) M cells. The possible functional reason for this transport is unknown. We
      have thus examined in mice the outcome of SIgA delivered from the intestinal
      lumen to the cells present in the underlying organized mucosa-associated
      lymphoreticular tissue. We show selective association of SIgA with dendritic
      cells and CD4(+) T and B lymphocytes recovered from PP in vitro. In vivo,
      exogenously delivered SIgA is able to enter into multiple PP lining the
      intestine. In PP, SIgA associates with and is internalized by dendritic cells in
      the subepithelial dome region, whereas the interaction with CD4(+) T cells is
      limited to surface binding. Interaction between cells and SIgA is mediated by the
      IgA moiety and occurs for polymeric and monomeric molecular forms. Thus, although
      immune exclusion represents the main function of SIgA, transport of the Ab by M
      cells might promote Ag sampling under neutralizing conditions essential to the
      homeostasis of mucosal surfaces.

PMID- 14978108
TI  - NK cells, but not NKT cells, are involved in Pseudomonas aeruginosa exotoxin A
      induced hepatotoxicity in mice.
AB  - Pseudomonas aeruginosa exotoxin A (PEA) causes T cell- and Kupffer cell (KC)
      dependent liver injury in mice. TNF-alpha as well as IL-18 and perforin are
      important mediators of liver damage following PEA injection. In this study, we
      focus on the role of NK and NKT cells in PEA-induced liver toxicity. Depletion of
      both NK and NKT cells by injection of anti-NK1.1 Ab as well as depletion of NK
      cells alone by anti-asialo GM1 Ab protected mice from PEA-induced hepatotoxicity,
      whereas mice lacking only NKT cells were susceptible. Additionally, we observed
      infiltration of NK cells, T cells, and neutrophils into liver parenchyma after
      injection of PEA. The number of NKT cells, however, remained unchanged. The
      increase in intrahepatic NK cells depended on KCs and the TNF-alpha-dependent up
      regulation of the adhesion molecule VCAM-1 in the liver, but not on NKT cells.
      PEA also augmented the cytotoxicity of hepatic NK cells against typical NK target
      cells (YAC-1 cells). This effect depended on KCs, but not on TNF-alpha or NKT
      cells. Furthermore, only weak expression of MHC class I was detected on
      hepatocytes, which was further down-regulated in PEA-treated mice. This could
      explain the susceptibility of hepatocytes to NK cell cytolytic activity in this
      model. Our results demonstrate that NK cells, activated and recruited
      independently of NKT cells, contribute to PEA-induced T cell-dependent liver
      injury in mice.

PMID- 14978109
TI  - The classical activation pathway of the human complement system is specifically
      inhibited by calreticulin from Trypanosoma cruzi.
AB  - The high resistance of Trypanosoma cruzi trypomastigotes, the causal agent of
      Chagas' disease, to complement involves several parasite strategies. In these in
      vitro studies, we show that T. cruzi calreticulin (TcCRT) and two subfragments
      thereof (TcCRT S and TcCRT R domains) bind specifically to recognition
      subcomponents of the classical and lectin activation pathways (i.e., to
      collagenous tails of C1q and to mannan-binding lectin) of the human complement
      system. As a consequence of this binding, specific functional inhibition of the
      classical pathway and impaired mannan-binding lectin to mannose were observed. By
      flow cytometry, TcCRT was detected on the surface of viable trypomastigotes and,
      by confocal microscopy, colocalization of human C1q with surface TcCRT of
      infective trypomastigotes was visualized. Taken together, these findings imply
      that TcCRT may be a critical factor contributing to the ability of
      trypomastigotes to interfere at the earliest stages of complement activation.

PMID- 14978110
TI  - Role of nicotinamide adenine dinucleotide phosphate oxidase 1 in oxidative burst
      response to Toll-like receptor 5 signaling in large intestinal epithelial cells.
AB  - The NADPH oxidase 1 (Nox1) is a gp91(phox) homologue preferentially expressed in
      the colon. We have established primary cultures of guinea pig large intestinal
      epithelial cells giving 90% purity of surface mucous cells. These cells
      spontaneously released superoxide anion (O(2)(-)) of 160 nmol/mg protein/h and
      expressed the Nox1, p22(phox), p67(phox), and Rac1 mRNAs, but not the gp91(phox),
      Nox4, p47(phox), p40(phox), and Rac2 mRNAs. They also expressed novel homologues
      of p47(phox) and p67(phox) (p41(nox) and p51(nox), respectively). Human colon
      cancer cell lines (T84 and Caco2 cells) expressed the Nox1, p22(phox), p51(nox),
      and Rac1 mRNAs, but not the other NADPH component mRNAs, and secreted only small
      amounts of O(2)(-) (<2 nmol/mg protein/h). Cotransfection of p41(nox) and
      p51(nox) cDNAs in T84 cells enhanced PMA-stimulated O(2)(-) release 5-fold.
      Treatment of the transfected T84 cells with recombinant flagellin (rFliC) from
      Salmonella enteritidis further augmented the O(2)(-) release in association with
      the induction of Nox1 protein. The enhanced O(2)(-) production by cotransfection
      of p41(nox) and p51(nox) vectors further augmented the rFliC-stimulated IL-8
      release from T84 cells. T84 cells expressed the Toll-like receptor 5, and rFliC
      rapidly phosphorylated TGF-beta-activated kinase 1 and TGF-beta-activated kinase
      1-binding protein 1. A potent inhibitor for NF-kappaB (pyrrolidine
      dithiocarbamate) significantly blocked the rFliC-primed increase in O(2)(-)
      production and induction of Nox1 protein. These results suggest that p41(nox) and
      p51(nox) are involved in the Nox1 activation in surface mucous cells of the
      colon, and besides that, epithelial cells discern pathogenicities among bacteria
      to appropriately operate Nox1 for the host defense.

PMID- 14978111
TI  - The contribution of the Toll-like/IL-1 receptor superfamily to innate and
      adaptive immunity to fungal pathogens in vivo.
AB  - In vitro studies have indicated the importance of Toll-like receptor (TLR)
      signaling in response to the fungal pathogens Candida albicans and Aspergillus
      fumigatus. However, the functional consequences of the complex interplay between
      fungal morphogenesis and TLR signaling in vivo remain largely undefined. In this
      study we evaluate the impact of the IL-1R/TLR/myeloid differentiation primary
      response gene 88 (MyD88)-dependent signaling pathway on the innate and adaptive
      Th immunities to C. albicans and A. fumigatus in vivo. It was found that 1) the
      MyD88-dependent pathway is required for resistance to both fungi; 2) the
      involvement of the MyD88 adapter may occur through signaling by distinct members
      of the IL-1R/TLR superfamily, including IL-1R, TLR2, TLR4, and TLR9, with the
      proportional role of the individual receptors varying depending on fungal
      species, fungal morphotypes, and route of infection; 3) individual TLRs and IL-1R
      activate specialized antifungal effector functions on neutrophils, which
      correlates with susceptibility to infection; and 4) MyD88-dependent signaling on
      dendritic cells is crucial for priming antifungal Th1 responses. Thus, the
      finding that the innate and adaptive immunities to C. albicans and A. fumigatus
      require the coordinated action of distinct members of the IL-1R/TLR superfamily
      acting through MyD88 makes TLR manipulation amenable to the induction of host
      resistance to fungi.

PMID- 14978112
TI  - Postsecretory processing generates multiple cathelicidins for enhanced topical
      antimicrobial defense.
AB  - The production of antimicrobial peptides and proteins is essential for defense
      against infection. Many of the known human antimicrobial peptides are
      multifunctional, with stimulatory activities such as chemotaxis while
      simultaneously acting as natural antibiotics. In humans, eccrine appendages
      express DCD and CAMP, genes encoding proteins processed into the antimicrobial
      peptides dermcidin and LL-37. In this study we show that after secretion onto the
      skin surface, the CAMP gene product is processed by a serine protease-dependent
      mechanism into multiple novel antimicrobial peptides distinct from the
      cathelicidin LL-37. These peptides show enhanced antimicrobial action, acquiring
      the ability to kill skin pathogens such as Staphylococcus aureus and Candida
      albicans. Furthermore, although LL-37 may influence the host inflammatory
      response by stimulating IL-8 release from keratinocytes, this activity is lost in
      subsequently processed peptides. Thus, a single gene product encoding an
      important defense molecule alters structure and function in the topical
      environment to shift the balance of activity toward direct inhibition of
      microbial colonization.

PMID- 14978114
TI  - Leishmania infantum promotes replication of HIV type 1 in human lymphoid tissue
      cultured ex vivo by inducing secretion of the proinflammatory cytokines TNF-alpha
      and IL-1 alpha.
AB  - Parasitic infections such as leishmaniasis can modulate the life cycle of HIV-1
      and disease progression. Coinfection with HIV-1 and Leishmania has emerged as a
      serious threat in countries where both pathogenic agents are widespread. Although
      there are numerous clinical reports illustrating the cofactor role played by
      Leishmania in HIV-1-infected patients, there is still no information on the
      contribution of Leishmania to the biology of HIV-1 in human lymphoid tissue that
      is considered a major in vivo site of virus production. In this study we explored
      the modulatory effect of Leishmania on the process of HIV-1 infection using ex
      vivo cultured human tonsillar tissue. We found that the protozoan parasite
      Leishmania enhances both HIV-1 transcription and virus production after infection
      of human tonsillar tissue infected ex vivo with viral strains bearing various
      coreceptor usage profiles. Studies conducted with pentoxifylline and neutralizing
      Abs revealed that the Leishmania-mediated increase in HIV-1 production was linked
      to a higher production of TNF-alpha and IL-1alpha. Our findings help to unravel
      the molecular mechanism(s) through which the two microorganisms interact and
      provide information that may be useful for the design of more effective
      therapeutic strategies aimed at controlling disease progression in persons dually
      infected with HIV-1 and Leishmania. This work also indicates that histocultures
      of human lymphoid tissue infected by both pathogens represent an ideal
      experimental cell system to dissect interactions occurring between HIV-1 and an
      opportunist pathogen in a human microenvironment that approximates conditions
      prevailing under physiological situations.

PMID- 14978113
TI  - T cell reactivity during infectious mononucleosis and persistent gammaherpesvirus
      infection in mice.
AB  - Intranasal infection of mice with murine gammaherpesvirus 68 causes a dramatic
      increase in numbers of activated CD8(+) T cells in the blood, analogous in many
      respects to EBV-induced infectious mononucleosis in humans. In the mouse model,
      this lymphocytosis has two distinct components: an early, conventional virus
      specific CD8(+) T cell response, and a later response characterized by a dramatic
      increase among CD8(+) T cells that bear Vbeta4(+) TCRs. We previously
      demonstrated that Vbeta4(+)CD8(+) T cells recognize an uncharacterized ligand
      expressed on latently infected B cells in an MHC-independent manner. The
      frequency of Vbeta4(+)CD8(+) T cells increases dramatically following the peak of
      viral latency in the spleen. In the current studies, we show that elevated
      Vbeta4(+)CD8(+) T cell levels are sustained long-term in persistently infected
      mice, apparently a consequence of continued ligand expression. In addition, we
      show that Vbeta4(+)CD8(+) T cells can acquire effector functions, including
      cytotoxicity and the capacity to secrete IFN-gamma, although they have an
      atypical activation profile compared with well-characterized CD8(+) T cells
      specific for conventional viral epitopes. The characteristics of Vbeta4(+)CD8(+)
      T cells (potential effector function, stimulation by latently infected B cells,
      and kinetics of expansion) suggested that this dominant T cell response plays a
      key role in the immune control of latent virus. However, Ab depletion and
      adoptive transfer studies show that Vbeta4(+)CD8(+) T cells are not essential for
      this function. This murine model of infection may provide insight into the role
      of unusual populations of activated T cells associated with persistent viral
      infections.

PMID- 14978115
TI  - Enhanced CD8+ T cell immune responses and protection elicited against Plasmodium
      berghei malaria by prime boost immunization regimens using a novel attenuated
      fowlpox virus.
AB  - Sterile immunity can be provided against the pre-erythrocytic stages of malaria
      by IFN-gamma-secreting CD8(+) T cells that recognize parasite-infected
      hepatocytes. In this study, we have investigated the use of attenuated fowlpox
      virus (FPV) strains as recombinant vaccine vectors for eliciting CD8(+) T cells
      against Plasmodium berghei. The gene encoding the P. berghei circumsporozoite
      (PbCS) protein was inserted into an FPV vaccine strain licensed for use in
      chickens, Webster's FPV, and the novel FPV vaccine strain FP9 by homologous
      recombination. The novel FP9 strain proved more potent as a vaccine for eliciting
      CD8(+) T cell responses against the PbCS Ag. Sequential immunization with rFP9
      and recombinant modified vaccinia virus Anakara (MVA) encoding the PbCS protein,
      administered by clinically acceptable routes, elicited potent CD8(+) T cell
      responses against the PbCS protein. This immunization regimen elicited
      substantial protection against a stringent liver-stage challenge with P. berghei
      and was more immunogenic and protective than DNA/MVA prime/boost immunization.
      However, further improvement was not achieved by sequential (triple) immunization
      with a DNA vaccine, FP9, and MVA.

PMID- 14978116
TI  - Hemozoin-inducible proinflammatory events in vivo: potential role in malaria
      infection.
AB  - During malaria infection, high levels of proinflammatory molecules (e.g.,
      cytokines, chemokines) correlate with disease severity. Even if their role as
      activators of the host immune response has been studied, the direct contribution
      of hemozoin (HZ), a parasite metabolite, to such a strong induction is not fully
      understood. Previous in vitro studies demonstrated that both Plasmodium
      falciparum HZ and synthetic HZ (sHZ), beta-hematin, induce macrophage/monocyte
      chemokine and proinflammatory cytokine secretion. In the present study, we
      investigated the proinflammatory properties of sHZ in vivo. To this end,
      increasing doses of sHZ were injected either i.v. or into an air pouch generated
      on the dorsum of BALB/c mice over a 24-h period. Our results showed that sHZ is a
      strong modulator of leukocyte recruitment and more specifically of neutrophil and
      monocyte populations. In addition, evaluation of chemokine and cytokine mRNA and
      protein expression revealed that sHZ induces the expression of chemokines,
      macrophage-inflammatory protein (MIP)-1alpha/CCL3, MIP-1beta/CCL4, MIP-2/CXCL2,
      and monocyte chemoattractant protein-1/CCL2; chemokine receptors, CCR1, CCR2,
      CCR5, CXCR2, and CXCR4; cytokines, IL-1beta and IL-6; and myeloid-related
      proteins, S100A8, S100A9, and S100A8/A9, in the air pouch exudates. Of interest,
      chemokine and cytokine mRNA up-regulation were also detected in the liver of i.v.
      sHZ-injected mice. In conclusion, our study demonstrates that sHZ is a potent
      proinflammatory agent in vivo, which could contribute to the immunopathology
      related to malaria.

PMID- 14978117
TI  - The group B streptococcal beta and pneumococcal Hic proteins are structurally
      related immune evasion molecules that bind the complement inhibitor factor H in
      an analogous fashion.
AB  - Complement evasion by different mechanisms is important for microbial virulence
      and survival in the host. One strategy used by pathogenic bacteria is to bind the
      soluble complement inhibitor factor H (fH) to their surfaces. In group B
      streptococci and pneumococci, fH binding has been shown to be mediated by the
      surface proteins beta and Hic, respectively. We showed previously that Hic binds
      to the middle region of fH and protects the pneumococcus from opsonophagocytosis.
      As the beta protein and Hic are structurally closely related, we wanted to
      compare the fH binding characteristics of these two proteins. By using direct
      binding assays with radiolabeled proteins and surface plasmon resonance analysis
      we show that both beta and Hic bind to the short consensus repeats 8-11 and 12-14
      in the middle region of fH. Peptide mapping analysis suggested that the fH
      binding sites on beta and Hic were composed of discontinuous and partially
      homologous sequences. Thus, the bacterial virulence proteins use multiple binding
      sites on fH to secure high avidity. Also, the functionally active sites on fH are
      thereby left free to inhibit C3b deposition and opsonophagocytosis. These results
      reveal the evolutionary conservation of an analogous immune evasion strategy in
      different types of pathogenic streptococci. Importantly, the respective virulence
      factors could be exploited in the development of protein-based vaccines against
      these pathogens.

PMID- 14978118
TI  - Coordinate expression of cytokines and chemokines by NK cells during murine
      cytomegalovirus infection.
AB  - Cytokines and chemokines activate and direct effector cells during infection. We
      previously identified a functional group of five cytokines and chemokines,
      namely, IFN-gamma, activation-induced T cell-derived and chemokine-related
      cytokine/lymphotactin, macrophage-inflammatory protein 1alpha, macrophage
      inflammatory protein 1beta, and RANTES, coexpressed in individual activated NK
      cells, CD8(+) T cells, and CD4(+) Th1 cells in vitro and during in vivo
      infections. However, the stimuli during infection were not known. In murine CMV
      (MCMV) infection, the DAP12/KARAP-associated Ly49H NK cell activation receptor is
      crucial for resistance through recognition of MCMV-encoded m157 but NK cells also
      undergo in vivo nonspecific responses to uncharacterized stimuli. In this study,
      we show that Ly49H ligation by m157 resulted in a coordinated release of all five
      cytokines/chemokines from Ly49H(+) NK cells. Whereas other cytokines also
      triggered the release of these cytokines/chemokines, stimulation was not confined
      to the Ly49H(+) population. At the single-cell level, the production of the five
      mediators showed strong positive correlation with each other. Interestingly, NK
      cells were a major source of these five cytokines/chemokines in vitro and in
      vivo, whereas infected macrophages produced only limited amounts of macrophage
      inflammatory protein 1alpha, macrophage-inflammatory protein1beta, and RANTES.
      These findings suggest that both virus-specific and nonspecific NK cells play
      crucial roles in activating and directing other inflammatory cells during MCMV
      infection.

PMID- 14978119
TI  - Toll-like receptor 2 plays a role in the early inflammatory response to murine
      pneumococcal pneumonia but does not contribute to antibacterial defense.
AB  - Toll-like receptors (TLR) are crucial pattern recognition receptors in innate
      immunity. The importance of TLR2 in host defense against Gram-positive bacteria
      has been suggested by the fact that this receptor recognizes major Gram-positive
      cell wall components, such as peptidoglycan and lipoteichoic acid. To determine
      the role of TLR2 in pulmonary Gram-positive infection, we first established that
      TLR2 is indispensable for alveolar macrophage responsiveness toward Streptococcus
      pneumoniae. Nonetheless, TLR2 gene-deficient mice intranasally inoculated with S.
      pneumoniae at doses varying from nonlethal (with complete clearance of the
      infection) to lethal displayed only a modestly reduced inflammatory response in
      their lungs and an unaltered antibacterial defense when compared with normal wild
      type mice. These data suggest that TLR2 plays a limited role in the innate immune
      response to pneumococcal pneumonia, and that additional pattern recognition
      receptors likely are involved in host defense against this common respiratory
      pathogen.

PMID- 14978120
TI  - Comprehensive early and lasting loss of memory CD8 T cells and functional memory
      during acute and persistent viral infections.
AB  - Viral infections have been shown to induce lymphopenias that lower memory CD8 T
      cell frequencies, and they also have been shown to cause a permanent loss of
      memory cells specific to previously encountered pathogens. In this study, the
      patterns and significance of virus-induced memory CD8 T cell depletion were
      examined in mice immune to heterologous (Pichinde, vesicular stomatitis,
      vaccinia) viruses and subsequently challenged with acute or persistent
      lymphocytic choriomeningitis virus infections. Memory CD8 T cell loss was
      comprehensive and occurred in both lymphoid and peripheral tissues of the immune
      host. The impact of the loss of memory T cells was reflected by in vivo
      cytotoxicity assays, which showed decreased clearance of epitope-expressing
      targets. Memory CD8 T cell loss occurred very early (day 2) after infection, and
      was thereafter sustained, consistent more with an active deletion model than with
      a competition model. Cross-reactive T cells, in contrast, increased in number,
      but memory cells were reduced whether or not there was competition from cross
      reactive T cells. Memory T cell loss was more profound during persistent
      infection than after acute infection. Adoptive transfer studies showed that,
      unlike the resolved acute infection, in which the reduced memory frequencies
      became stable, memory T cell loss was a continuously ongoing process during
      persistent infection. This study therefore links an early virus-induced
      lymphopenia to a subsequent long-term loss of CD8 T cell memory and offers a new
      mechanism for immune deficiency during persistent viral infections.

PMID- 14978121
TI  - Very diverse CD8 T cell clonotypic responses after virus infections.
AB  - We measured CD8 T cell clonotypic diversity to three epitopes recognized in
      C57BL/6 mice infected with mouse hepatitis virus, strain JHM, or lymphocytic
      choriomeningitis virus. We isolated epitope-specific T cells with an IFN-gamma
      capture assay or MHC class I/peptide tetramers and identified different
      clonotypes by Vbeta chain sequence analysis. In agreement with our previous
      results, the number of different clonotypes responding to all three epitopes fit
      a log-series distribution. From these distributions, we estimated that >1000
      different clonotypes responded to each immunodominant CD8 T cell epitope; the
      response to a subdominant CD8 T cell epitope was modestly less diverse. These
      results suggest that T cell response diversity is greater by 1-2 orders of
      magnitude than predicted previously.

PMID- 14978122
TI  - The pathogenesis of schistosomiasis is controlled by cooperating IL-10-producing
      innate effector and regulatory T cells.
AB  - IL-10 reduces immunopathology in many persistent infections, yet the contribution
      of IL-10 from distinct cellular sources remains poorly defined. We generated IL
      10/recombination-activating gene (RAG)2-deficient mice and dissected the role of
      T cell- and non-T cell-derived IL-10 in schistosomiasis by performing adoptive
      transfers. In this study, we show that IL-10 is generated by both the innate and
      adaptive immune response following infection, with both sources regulating the
      development of type-2 immunity, immune-mediated pathology, and survival of the
      infected host. Importantly, most of the CD4(+) T cell-produced IL-10 was confined
      to a subset of T cells expressing CD25. These cells were isolated from egg
      induced granulomas and exhibited potent suppressive activity in vitro.
      Nevertheless, when naive, naturally occurring CD4(+)CD25(+) cells were depleted
      in adoptive transfers, recipient IL-10/RAG2-deficient animals were more
      susceptible than RAG2-deficient mice, confirming an additional host-protective
      role for non-T cell-derived IL-10. Thus, innate effectors and regulatory T cells
      producing IL-10 cooperate to reduce morbidity and prolong survival in
      schistosomiasis.

PMID- 14978123
TI  - Depletion of CD4+ T cells during immunization with nonviable Listeria
      monocytogenes causes enhanced CD8+ T cell-mediated protection against
      listeriosis.
AB  - Immunization of mice with nonviable Listeria monocytogenes generates an
      insufficient CD8(+) T cell response and consequently only limited protection
      against subsequent L. monocytogenes infection. We have recently demonstrated that
      depletion of regulatory CD4(+) T cells during immunization significantly enhances
      CD8(+) T cell responses. In the present study, we determined the impact of CD4(+)
      T cell depletion on the CD8(+) T cell response against heat-killed Listeria.
      Treatment of mice with anti-CD4 mAb during boost immunization with heat-killed
      Listeria significantly increased numbers of Listeria-specific CD8(+) T cells and
      improved protection against subsequent infection with L. monocytogenes. During
      challenge infection, numbers of Listeria-specific CD8(+) T cells were enhanced,
      and these cells expressed effector functions in terms of IFN-gamma production. In
      summary, we demonstrate that combining nonviable L. monocytogenes vaccination and
      CD4(+) T cell depletion improves generation of long-lasting and functional
      Listeria-specific CD8(+) memory T cells.

PMID- 14978124
TI  - The effect of innate immunity on autoimmune diabetes and the expression of Toll
      like receptors on pancreatic islets.
AB  - Viral infections have previously been implicated as a trigger of autoimmune
      diabetes. In this study, we compared a viral mimic with other microbial
      components derived from bacteria in triggering diabetes development in C57BL/6
      rat insulin promoter-B7.1 mice that do not normally develop diabetes. It is
      striking that only the viral mimic induced the development of diabetes in our
      model system. Further mechanistic studies suggest that diabetes is induced, in
      part, by the combination of direct recognition of this virus-like stimulus by
      pancreatic islets through the expression of the innate immune receptor, Toll-like
      receptor 3. In addition, the functions of APCs are up-regulated, and this could
      stimulate islet Ag-reactive T cells that will attack beta cells leading to
      autoimmune diabetes.

PMID- 14978125
TI  - IL-10 inhibits Fc epsilon RI expression in mouse mast cells.
AB  - FcepsilonRI expression and function is a central aspect of allergic disease.
      Using bone marrow-derived mouse mast cell populations, we have previously shown
      that the Th2 cytokine IL-4 inhibits FcepsilonRI expression and function. In the
      current study we show that the Th2 cytokine IL-10 has similar regulatory
      properties, and that it augments the inhibitory effects of IL-4. FcepsilonRI down
      regulation was functionally significant, as it diminished inflammatory cytokine
      production and IgE-mediated FcepsilonRI up-regulation. IL-10 and IL-4 reduced
      FcepsilonRI beta protein expression without altering the alpha or gamma subunits.
      The ability of IL-4 and IL-10 to alter FcepsilonRI expression by targeting the
      beta-chain, a critical receptor subunit known to modulate receptor expression and
      signaling, suggests the presence of a Th2 cytokine-mediated homeostatic network
      that could serve to both initiate and limit mast cell effector function.

PMID- 14978126
TI  - HIV-infected lymphocytes regulate fibronectin synthesis by TGF beta 1 secretion.
AB  - Alterations in lymph node architecture occur with HIV infection and contribute to
      immunological derangements. We previously showed that matrix fibronectin
      stabilized HIV and increased HIV infection of PBL. We showed increased
      fibronectin deposition in lymph nodes of HIV-infected patients. However, we did
      not detect a difference in fibronectin synthesis between uninfected and infected
      PBL. Therefore, we hypothesized that interactions of HIV-infected cells with
      fibroblasts resulted in increased fibronectin deposition. We detected increased
      fibronectin deposition by immunofluorescence on fibroblasts cocultured with HIV
      infected PBL. We also found a 6-fold increase in fibronectin mRNA levels in
      fibroblasts cocultured with HIV-infected PBL by real-time PCR. Furthermore, when
      HIV-infected PBL were added to reporter fibroblasts stably transfected with a
      fibronectin promoter, we found a 1.5- to 2-fold increase in promoter activity.
      Since conditioned medium from HIV-infected PBL also increased fibronectin
      promoter activity, we hypothesized that a soluble factor such as TGFbeta was
      responsible for increased fibronectin secretion. Pretreatment of supernatant from
      HIV-infected PBL with a neutralizing Ab to TGFbeta1 abrogated the increased
      fibronectin promoter activity. We confirmed that HIV-infected PBL produced
      increased TGFbeta1 by ELISA. Using Mv1Lu reporter cells, we found a 2- to 3-fold
      increase in biologically active TGFbeta in supernatants of HIV-infected PBL.
      Finally, we determined that HIV infection did not change the percentage of active
      TGFbeta. Our data suggest that HIV-infected lymphocytes indirectly contribute to
      lymph node remodeling by secretion of TGFbeta1, which increases fibronectin
      synthesis by fibroblasts.

PMID- 14978127
TI  - Acidosis improves uptake of antigens and MHC class I-restricted presentation by
      dendritic cells.
AB  - It is widely appreciated that inflammatory responses in peripheral tissues are
      usually associated to the development of acidic microenvironments. Despite this,
      there are few studies aimed to analyze the effect of extracellular pH on immune
      cell functions. We analyzed the impact of acidosis on the behavior of dendritic
      cells (DCs) derived from murine bone marrow. We found that extracellular acidosis
      (pH 6.5) markedly stimulated the uptake of FITC-OVA, FITC-dextran, and HRP by
      DCs. In fact, to reach similar levels of endocytosis, DCs cultured at pH 7.3
      required concentrations of Ag in the extracellular medium almost 10-fold higher
      compared with DCs cultured at pH 6.5. Not only the endocytic capacity of DCs was
      up-regulated by extracellular acidosis, but also the expression of CD11c, MHC
      class II, CD40, and CD86 as well as the acquisition of extracellular Ags by DCs
      for MHC class I-restricted presentation. Importantly, DCs pulsed with Ag under
      acidosis showed an improved efficacy to induce both specific CD8(+) CTLs and
      specific Ab responses in vivo. Our results suggest that extracellular acidosis
      improves the Ag-presenting capacity of DCs.

PMID- 14978129
TI  - Recruitment of IFN-gamma-producing (Th1-like) cells into the inflamed retina in
      vivo is preferentially regulated by P-selectin glycoprotein ligand 1:P/E-selectin
      interactions.
AB  - Although there is evidence that altering the Th1/Th2 balance toward Th2 cells may
      be important in the resolution of Th1-type autoimmune disease, adoptive transfer
      of Th2 cells is not effective in protecting against Th1-type disease and may
      cause disease. Therefore, we examined the recruitment of Th1- and Th2-like cells
      into the retina in the murine autoimmune disease experimental autoimmune
      uveoretinitis. CD4 T cells were polarized in vitro to IFN-gamma-producing Th1
      like cells and non-IFN-gamma-producing Th2-like cells, labeled, and adoptively
      transferred. Trafficking to the retina in vivo was evaluated by scanning laser
      ophthalmoscopy and infiltration by confocal microscopy. There were more rolling
      and adherent Th1-like cells and they rolled more slowly than did Th2-like cells.
      Th1-like cells were preferentially recruited into the retinal parenchyma at both
      initiation and resolution. Surface P-selectin glycoprotein ligand 1 (PSGL-1) and
      LFA-1 were up-regulated on both populations but were expressed at higher levels
      on Th1-like cells. Up-regulation of CD44 expression was higher on Th2-like cells.
      P-selectin, E-selectin, and ICAM-1 are up-regulated on postcapillary venules in
      the retina. Pretreatment of Th1-like cells with anti-PSGL-1 inhibited rolling and
      infiltration of Th1-like cells but not Th2-like cells, providing direct in vivo
      evidence for the inability of Th2 to respond to P/E-selectin despite increased
      expression of PSGL-1. Anti-LFA-1 pretreatment inhibited infiltration of both Th1-
      and Th2-like cells, but more so Th-1. We suggest that random trafficking of
      activated T cells (both Th1 and Th2) across the blood-retina barrier is mediated
      by CD44:CD44R and LFA-1:ICAM-1, whereas preferential recruitment of Th1 cells is
      mediated by PSGL-1:P/E-selectin.

PMID- 14978128
TI  - CD40 on adult human airway epithelial cells: expression and proinflammatory
      effects.
AB  - CD40/CD40 ligand interaction is an important pathway for B and T cell cooperation
      and function; functional CD40 molecules have recently been found on
      nonhematopoietic cells. We detected CD40 in vivo on normal human respiratory
      epithelial cells and showed that its expression is increased on inflamed airway
      epithelium. Subsequently, we analyzed its expression and function on primary
      cultures of human airway epithelial cells. Our data show that CD40 is up
      regulated by IFN-beta and IFN-gamma, its ligation increases the surface
      expression of CD54 and CD106 and it may stimulate the release of IL-6 and IL-8.
      The use of Janus kinase 3 (JAK3) and NF-kappaB inhibitors suggests that both
      basal and CD40-induced release of the two cytokines is JAK3-dependent. Using
      colocalization techniques, we revealed the existence of CD40/JAK3 and CD40/TNFR
      associated factor 2 interplay. The extent of these interactions may be partial (2
      40% of the cells) or massive (80-90% of the cells) in cultured cells. Stimulation
      via CD40 causes a significant increase in the number of cells expressing
      colocalization only in the cultures displaying low frequency of initial
      colocalization. Thus, airway epithelial cells, activated by CD40, may behave as
      effector cells of the inflammation process and should be considered priority
      targets for anti-inflammatory therapy. This work identifies CD40 and the
      correlated JAK3 signaling molecule as potential molecular targets to block the
      inflammatory functions of epithelial cells.

PMID- 14978130
TI  - Cryptic epitope identified in rat and human cardiac myosin S2 region induces
      myocarditis in the Lewis rat.
AB  - Myocarditis is a common cause of dilated cardiomyopathy leading to heart failure.
      Chronic stages of myocarditis may be initiated by autoimmune responses to exposed
      cardiac Ags after myocyte damage. Cardiac myosin, a heart autoantigen, induced
      experimental autoimmune myocarditis (EAM) in susceptible animals. Although
      cardiac myosin-induced myocarditis has been reported in Lewis rats, the main
      pathogenic epitope has not been identified. Using overlapping synthetic peptides
      of the S2 region of human cardiac myosin, we identified an amino acid sequence,
      S2-16 (residues 1052-1076), that induced severe myocarditis in Lewis rats. The
      myocarditic epitope was localized to a truncated S2-16 peptide (residues 1052
      1073), which contained a sequence identical in human and rat cardiac myosin. The
      S2-16 peptide was not myocarditic for three other strains of rats, in which the
      lack of myocarditis was accompanied by the absence of strong S2-16-specific
      lymphocyte responses in vitro. For Lewis rats, S2-16 was characterized as a
      cryptic epitope of cardiac myosin because it did not recall lymphocyte and Ab
      responses after immunization with cardiac myosin. Lymphocytes from S2-16
      immunized rats recognized not only S2-16, but also peptides in the S2-28 region.
      Furthermore, peptide S2-28 was the dominant epitope recognized by T cells from
      cardiac myosin immunized rats. S2-16 was presented by Lewis rat MHC class II
      molecules, and myocarditis induction was associated with an up-regulation of
      inflammatory cytokine production. S2-16-induced EAM provides a defined animal
      model to investigate mechanisms of EAM and modulation of immune responses to
      prevent autoimmune myocarditis.

PMID- 14978131
TI  - Direct in vivo monitoring of acute allergic reactions in human conjunctiva.
AB  - Immediate allergic reactions are initiated by allergen-induced, specific IgE
      mediated mast cell degranulation and involve leukocyte recruitment into the
      inflamed site. We compared conjunctival signs, symptoms, and in vivo leukocyte
      rolling and extravasation into sites of inflammation in five patients allergic to
      birch pollen and in 10 nonallergic controls who received a challenge to birch
      allergen or histamine. Both the specific allergen in allergic patients and
      histamine, both in patients and in healthy controls, induced symptoms and signs
      of an immediate allergic reaction together with leukocyte rolling within the
      conjunctival blood vessels. However, only allergen, not histamine, caused
      leukocyte extravasation into the site of inflammation in the allergic patients.
      Allergen also increased expression of endothelial P-selectin in conjunctival
      vessels and slowed the rolling of leukocytes which is required for their
      extravasation from blood circulation into the target tissue. Finally, i.v.
      heparin strongly reduced the number of slowly rolling cells during allergen- or
      histamine-induced reactions and this can probably hinder the leukocyte
      extravasation after allergen exposure. These findings suggest that slow rolling
      is required for leukocyte extravasation in acute allergic reactions, and it can
      be inhibited by heparin in vivo in therapeutically relevant conditions.

PMID- 14978132
TI  - Long-term suppression of tumor growth by TNF requires a Stat1- and IFN regulatory
      factor 1-dependent IFN-gamma pathway but not IL-12 or IL-18.
AB  - Tumor cells engineered to secrete TNF were used as a model to examine how
      persistently high local concentrations of TNF suppress tumor growth. TNF
      secretion had no effect on tumor cell proliferation in vitro but caused a very
      impressive growth arrest in vivo that was dependent on both bone marrow- and non
      bone marrow-derived host cells expressing TNFR. Suppression also required an
      endogenous IFN-gamma pathway consisting minimally of IFN-gamma, IFN-gamma
      receptor, Stat1, and IFN regulatory factor 1 since mice with targeted disruption
      of any of the four genes failed to arrest tumor growth. The ability of these mice
      to suppress tumor growth was restored after they were reconstituted with bone
      marrow cells from Wt mice. Interestingly, mice lacking the major IFN-gamma
      inducing cytokines IL-12 and IL-18 or T cells, B cells, and the majority of NK
      cells that are potential sources of IFN-gamma nevertheless inhibited tumor
      development. Moreover, multiple lines of evidence indicated that local release of
      IFN-gamma was not required to inhibit tumor formation. These results strongly
      suggest a novel function for the endogenous IFN-gamma pathway that without
      measurable IFN-gamma production or activity affects the ability of TNF to
      suppress tumor development.

PMID- 14978133
TI  - Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and
      blocking IgG activity.
AB  - T regulatory cells and IL-10 have been implicated in the mechanism of
      immunotherapy in patients with systemic anaphylaxis following bee stings. We
      studied the role of IL-10 in the induction of clinical, cellular, and humoral
      tolerance during immunotherapy for local mucosal allergy in subjects with
      seasonal pollinosis. Local and systemic IL-10 responses and serum Ab
      concentrations were measured before/after a double-blind trial of grass pollen
      (Phleum pratense, Phl P) immunotherapy. We observed local increases in IL-10 mRNA
      positive cells in the nasal mucosa after 2 years of immunotherapy, but only
      during the pollen season. IL-10 protein-positive cells were also increased and
      correlated with IL-10 mRNA(+) cells. These changes were not observed in placebo
      treated subjects or in healthy controls. Fifteen and 35% of IL-10 mRNA signals
      were colocalized to CD3(+) T cells and CD68(+) macrophages, respectively, whereas
      only 1-2% of total CD3(+) cells and 4% of macrophages expressed IL-10. Following
      immunotherapy, peripheral T cells cultured in the presence of grass pollen
      extract also produced IL-10. Immunotherapy resulted in blunting of seasonal
      increases in serum allergen Phl p 5-specific IgE, 60- to 80-fold increases in Phl
      p 5-specific IgG, and 100-fold increases in Phl p 5-specific IgG4. Post
      immunotherapy serum exhibited inhibitory activity, which coeluted with IgG4, and
      blocked IgE-facilitated binding of allergen-IgE complexes to B cells. Both the
      increases in IgG and the IgG "blocking" activity correlated with the patients'
      overall assessment of improvement. Thus, grass pollen immunotherapy may induce
      allergen-specific, IL-10-dependent "protective" IgG4 responses.

PMID- 14978135
TI  - Lymphoma B cells evade apoptosis through the TNF family members BAFF/BLyS and
      APRIL.
AB  - The mechanisms underlying the autonomous accumulation of malignant B cells remain
      elusive. We show in this study that non-Hodgkin's lymphoma (NHL) B cells express
      B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing
      ligand (APRIL), two powerful B cell-activating molecules usually expressed by
      myeloid cells. In addition, NHL B cells express BAFF receptor, which binds BAFF,
      as well as transmembrane activator and calcium modulator and cyclophilin ligand
      interactor (TACI) and B cell maturation Ag (BCMA), which bind both BAFF and
      APRIL. Neutralization of endogenous BAFF and APRIL by soluble TACI and BCMA decoy
      receptors attenuates the survival of NHL B cells, decreases activation of the
      prosurvival transcription factor NF-kappaB, down-regulates the antiapoptotic
      proteins Bcl-2 and Bcl-x(L), and up-regulates the proapoptotic protein Bax.
      Conversely, exposure of NHL B cells to recombinant or myeloid cell-derived BAFF
      and APRIL attenuates apoptosis, increases NF-kappaB activation, up-regulates Bcl
      2 and Bcl-x(L), and down-regulates Bax. In some NHLs, exogenous BAFF and APRIL up
      regulate c-Myc, an inducer of cell proliferation; down-regulate p53, an inhibitor
      of cell proliferation; and increase Bcl-6, an inhibitor of B cell
      differentiation. By showing that nonmalignant B cells up-regulate BAFF and APRIL
      upon stimulation by T cell CD40 ligand, our findings indicate that NHL B cells
      deregulate an otherwise physiological autocrine survival pathway to evade
      apoptosis. Thus, neutralization of BAFF and APRIL by soluble TACI and BCMA decoy
      receptors could be useful to dampen the accumulation of malignant B cells in NHL
      patients.

PMID- 14978134
TI  - Persistent and selective deficiency of CD4+ T cell immunity to cytomegalovirus in
      immunocompetent young children.
AB  - Healthy young children who acquire CMV have prolonged viral shedding into the
      urine and saliva, but whether this is attributable to limitations in viral
      specific immune responses has not been explored. In this study, we found that
      otherwise immunocompetent young children after recent primary CMV infection
      accumulated markedly fewer CMV-specific CD4(+) T cells that produced IFN-gamma
      than did adults. These differences in CD4(+) T cell function persisted for more
      than 1 year after viral acquisition, and did not apply to CMV-specific IFN-gamma
      production by CD8(+) T cells. The IFN-gamma-producing CD4(+) T cells of children
      or adults that were reactive with CMV Ags were mainly the CCR7(low) cell subset
      of memory (CD45R0(high)CD45RA(low)) cells. The decreased IFN-gamma response to
      CMV in children was selective, because their CCR7(low) memory CD4(+) T cells and
      those of adults produced similar levels of this cytokine after stimulation with
      staphylococcal enterotoxin B superantigen. CD4(+) T cells from children also had
      reduced CMV-specific IL-2 and CD154 (CD40 ligand) expression, suggesting an early
      blockade in the differentiation of viral-specific CD4(+) T cells. Following CMV
      acquisition, children, but not adults, persistently shed virus in urine, and this
      was observable for at least 29 mo postinfection. Thus, CD4(+) T cell-mediated
      immunity to CMV in humans is generated in an age-dependent manner, and may have a
      substantial role in controlling renal viral replication and urinary shedding.

PMID- 14978136
TI  - Rituximab infusion promotes rapid complement depletion and acute CD20 loss in
      chronic lymphocytic leukemia.
AB  - Complement plays an important role in the immunotherapeutic action of the anti
      CD20 mAb rituximab, and therefore we investigated whether complement might be the
      limiting factor in rituximab therapy. Our in vitro studies indicate that at high
      cell densities, binding of rituximab to human CD20(+) cells leads to loss of
      complement activity and consumption of component C2. Infusion of rituximab in
      chronic lymphocytic leukemia patients also depletes complement; sera of treated
      patients have reduced capacity to C3b opsonize and kill CD20(+) cells unless
      supplemented with normal serum or component C2. Initiation of rituximab infusion
      in chronic lymphocytic leukemia patients leads to rapid clearance of CD20(+)
      cells. However, substantial numbers of B cells, with significantly reduced levels
      of CD20, return to the bloodstream immediately after rituximab infusion. In
      addition, a mAb specific for the Fc region of rituximab does not bind to these
      recirculating cells, suggesting that the rituximab-opsonized cells were
      temporarily sequestered by the mononuclear phagocytic system, and then released
      back into the circulation after the rituximab-CD20 complexes were removed by
      phagocytic cells. Western blots provide additional evidence for this escape
      mechanism that appears to occur as a consequence of CD20 loss. Treatment
      paradigms to prevent this escape, such as use of engineered or alternative anti
      CD20 mAbs, may allow for more effective immunotherapy of chronic lymphocytic
      leukemia.

PMID- 14978137
TI  - Vaccine-induced CD4+ T cell responses to MAGE-3 protein in lung cancer patients.
AB  - MAGE-3 is the most commonly expressed cancer testis Ag and thus represents a
      prime target for cancer vaccines, despite infrequent natural occurrence of MAGE-3
      specific immune responses in vivo. We report in this study the successful
      induction of Ab, CD8(+), and CD4(+) T cells in nonsmall cell lung cancer patients
      vaccinated with MAGE-3 recombinant protein. Two cohorts were analyzed: one
      receiving MAGE-3 protein alone, and one receiving MAGE-3 protein with adjuvant
      AS02B. Of nine patients in the first cohort, three developed marginal Ab titers
      and another one had a CD8(+) T cell response to HLA-A2-restricted peptide MAGE-3
      271-279. In contrast, of eight patients from the second cohort vaccinated with
      MAGE-3 protein and adjuvant, seven developed high-titered Abs to MAGE-3, and four
      had a strong concomitant CD4(+) T cell response to HLA-DP4-restricted peptide 243
      258. One patient simultaneously developed CD8(+) T cells to HLA-A1-restricted
      peptide 168-176. The novel monitoring methodology used in this MAGE-3 study
      establishes that protein vaccination induces clear CD4(+) T cell responses that
      correlate with Ab production. This development provides the framework for further
      evaluating integrated immune responses in vaccine settings and for optimizing
      these responses for clinical benefit.

PMID- 14978138
TI  - Role of specific CD8+ T cells in the severity of a fulminant zoonotic viral
      hemorrhagic fever, hantavirus pulmonary syndrome.
AB  - We report on the role of specific CD8(+) T cells in the pathogenesis of a highly
      lethal human viral disease, hantavirus pulmonary syndrome (HPS). HPS is a
      zoonotic disease caused by transmission of Sin Nombre virus (SNV) from
      chronically infected deer mice. In humans, this fulminant infection is
      characterized by lung capillary leakage, respiratory failure, and cardiogenic
      shock. Individuals with HLA-B*3501 have an increased risk of developing severe
      HPS, suggesting that CD8(+) T cell responses to SNV contribute to pathogenesis.
      We identified three CD8(+) T cell epitopes in SNV presented by HLA-B*3501 and
      quantitated circulating SNV-specific CD8(+) T cells in 11 acute HPS patients
      using HLA/peptide tetramers. We found significantly higher frequencies of SNV
      specific T cells in patients with severe HPS requiring mechanical ventilation (up
      to 44.2% of CD8(+) T cells) than in moderately ill HPS patients hospitalized but
      not requiring mechanical ventilation (up to 9.8% of CD8(+) T cells). These
      results imply that virus-specific CD8(+) T cells contribute to HPS disease
      outcome. Intense CD8(+) T cell responses to SNV may be induced by the encounter
      of the unnatural human host to this zoonotic virus without coevolution. This may
      also be the immunopathologic basis of other life-threatening human virus
      infections.

PMID- 14978139
TI  - Human memory B cells transferred by allogenic bone marrow transplantation
      contribute significantly to the antibody repertoire of the recipient.
AB  - The bone marrow is an important source of Abs involved in long-term protection
      from recurrence of infections. Allogenic bone marrow transplantation (BMT) fails
      to restore this working memory. Attempts to overcome this immunodeficiency by
      immunization of the donor have not been very successful. More needs to be known
      about transfer of B cell memory by BMT. We tracked memory B cells from the donor
      to the recipient during BMT of a girl with leukocyte adhesion deficiency.
      Vaccination of her HLA-identical sibling donor 7 days before harvest induced
      Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP)-specific B
      cells readily detectable in marrow and blood. BMT did not lead to spontaneous
      production of HibCP Abs, but the recipient responded well to booster
      immunizations 9 and 11 mo after BMT. HibCP-specific B cells were obtained 7 days
      after the vaccinations, and their V(H) genes were sequenced and analyzed for
      rearrangements and unique patterns of somatic hypermutations identifying clonally
      related cells. Ninety (74%) of 121 sequences were derived from only 16
      precursors. Twelve clones were identified in the donor, and representatives from
      all of them were detected in the recipient where they constituted 61 and 68% of
      the responding B cells after the first and second vaccinations, respectively. No
      evidence for re-entry of memory clones into the process of somatic hypermutation
      was seen in the recipient. Thus, memory B cells were transferred from the donor,
      persisted for at least 9 mo in the recipient, and constituted the major part of
      the HibCP-specific repertoire.

PMID- 14978140
TI  - Molecular and immunological evaluation of the transcription factor SOX-4 as a
      lung tumor vaccine antigen.
AB  - The developmental transcription factor SOX-4 has been shown to be highly and
      differentially overexpressed in primary small cell lung carcinomas (SCLC). To
      examine the potential of SOX-4 for broad use as a lung cancer vaccine, we have
      evaluated the expression of SOX-4 in a panel of primary adenocarcinoma, squamous,
      and large cell tumor samples as well as in a panel of established small cell and
      non-small cell lung carcinoma tumor cell lines. SOX-4 mRNA is shown to be
      overexpressed in a substantial fraction of each of these lung tumor types. To
      examine the immunological potential of SOX-4, we have evaluated the presence of
      SOX-4-specific CD4 and CD8 T cells in PBMC of healthy donors and the presence of
      SOX4-specific Abs in sera from SCLC patients. We demonstrate the presence of both
      CD4 and CD8 T cells that recognize naturally processed epitopes derived from SOX
      4 as well as the presence of SOX-4-specific Abs in sera from SCLC patients, but
      not in sera from healthy donors. The lung tumor-specific overexpression and
      demonstration of a comprehensive Ag-specific immune response specific for SOX-4
      support the use of this molecule in the development of whole gene-, peptide-, or
      protein-based vaccination strategies against lung cancer. Furthermore, the
      identification of naturally processed T cell and Ab epitopes from SOX-4 provides
      valuable tools for the development of peptide-based vaccination strategies
      against lung cancer as well as to monitor SOX-4-specific responses in vaccinated
      patients.

PMID- 14978141
TI  - Host conditioning is a primary determinant in modulating the effect of IL-7 on
      murine graft-versus-host disease.
AB  - Interleukin-7 has been shown to enhance T cell reconstitution after allogeneic
      bone marrow transplantation, in part, by expansion of mature donor T cells, but
      whether IL-7 also exacerbates graft-vs-host disease (GVHD) remains unresolved. To
      address this issue, we examined the effect of IL-7 on GVHD induction using a well
      defined murine GVHD model (B6-->B6AF1/J). Administration of IL-7 to nonirradiated
      B6AF1/J recipients of B6 T cells resulted in expansion of splenic donor CD4(+)
      and CD8(+) T cells and increased GVHD mortality. In contrast, administration of
      IL-7 on the same schedule failed to increase GVHD mortality in either sublethally
      or lethally irradiated animals that received graded doses of T cells designed to
      induce varying degrees of GVHD severity. Moreover, IL-7 failed to increase the
      number of alloreactive T cells when examined in a murine model (B6-->BALB.B) that
      allowed for direct quantitation of graft-vs-host-reactive T cells. The
      combination of irradiation and transplantation of alloreactive donor T cells
      resulted in significantly increased levels of endogenous splenic IL-7 mRNA when
      compared with nonirradiated transplanted animals, providing a potential
      explanation for why exogenous IL-7 did not increase GVHD severity in these mice.
      We conclude that host conditioning modulates the ability of exogenous IL-7 to
      exacerbate GVHD and that this occurs through induction of endogenous IL-7
      production.

PMID- 14978142
TI  - Effects of sustained HIV-1 plasma viremia on HIV-1 Gag-specific CD4+ T cell
      maturation and function.
AB  - An in vitro proliferative defect has been observed in HIV-1-specific CD4(+) T
      cells from infected subjects with high-level plasma HIV-1 viremia. To determine
      the mechanism of this defect, HIV-1 Gag-specific CD4(+) T cells from treated and
      untreated HIV-1-infected subjects were analyzed for cytokine profile,
      proliferative capacity, and maturation state. Unexpectedly high frequencies of
      HIV-1-specific, IL-2-producing CD4(+) T cells were measured in subjects with low
      or undetectable plasma HIV-1 loads, regardless of treatment status, and IL-2
      frequencies correlated inversely with viral loads. IL-2-producing CD4(+) T cells
      also primarily displayed a central memory (T(Cm); CCR7(+)CD45RA(-)) maturation
      phenotype, whereas IFN-gamma-producing cells were mostly effector memory (T(Em),
      CCR7(-)CD45RA(-)). Among Gag-specific, IFN-gamma-producing CD4(+) T cells, higher
      T(Em) frequencies and lower T(Cm) frequencies were observed in untreated, high
      viral load subjects than in subjects with low viral loads. The percentage of HIV
      1 Gag-specific CD4(+) T(Cm) correlated inversely with HIV-1 viral load and
      directly with Gag-specific CD4(+) T cell proliferation, whereas the opposite
      relationships were observed for HIV-1-specific CD4(+) T(Em). These results
      suggest that HIV-1 viremia skews Gag-specific CD4(+) T cells away from an IL-2
      producing T(Cm) phenotype and toward a poorly proliferating T(Em) phenotype,
      which may limit the effectiveness of the HIV-1-specific immune response.